1 00:00:04,243 --> 00:00:07,747 ON BEHALF OF THE DIVISION OF 2 00:00:07,747 --> 00:00:11,217 BLOOD DISEASES I WELCOME YOU TO 3 00:00:11,217 --> 00:00:15,588 THIS WORKSHOP, UNRAVELING 4 00:00:15,588 --> 00:00:16,489 SEPSIS, HEALTH INEQUITIES, 5 00:00:16,489 --> 00:00:20,092 THROMBO INFLAMMATION MECHANIC 6 00:00:20,092 --> 00:00:20,959 NICHES AND AI/ML FRONTIERS. 7 00:00:20,959 --> 00:00:25,998 IT'S A PLEASURE TO HAVE YOU TO 8 00:00:25,998 --> 00:00:26,799 IMPROVE HEALTH OUTCOMES. 9 00:00:26,799 --> 00:00:32,704 I WANT TO TAKE A MOMENT THANK 10 00:00:32,704 --> 00:00:37,843 THE NHLBI, ORGANIZERS, AND THE 11 00:00:37,843 --> 00:00:39,411 CHAIRS, WHO HAVE ALL GRACIOUSLY 12 00:00:39,411 --> 00:00:43,749 SHARED THEIR TIME TO HELP PUT 13 00:00:43,749 --> 00:00:44,850 THIS WORKSHOP TOGETHER. 14 00:00:44,850 --> 00:00:45,684 SEPSIS REMAINS A CRITICAL 15 00:00:45,684 --> 00:00:47,152 CHALLENGE AND CONTRIBUTES TO A 16 00:00:47,152 --> 00:00:48,887 BURDEN OF MORBIDITY AND 17 00:00:48,887 --> 00:00:49,454 MORTALITY. 18 00:00:49,454 --> 00:00:52,090 THE WORKSHOP TODAY AIMS TO 19 00:00:52,090 --> 00:00:53,525 ADDRESS THE COMPLEX CONDITION BY 20 00:00:53,525 --> 00:00:56,461 FOCUSING ON THESE THREE KEY 21 00:00:56,461 --> 00:00:58,096 RESEARCH AREAS, HEALTH 22 00:00:58,096 --> 00:00:59,231 INEQUITIES, MECHANISMS OF 23 00:00:59,231 --> 00:01:00,699 THROMBO INFLAMMATION, AND THE 24 00:01:00,699 --> 00:01:03,035 ROLE OF ARTIFICIAL INTELLIGENCE 25 00:01:03,035 --> 00:01:05,771 AND MACHINE LEARNING IN SEPSIS 26 00:01:05,771 --> 00:01:06,572 RESEARCH. 27 00:01:06,572 --> 00:01:08,507 THREE SESSIONS WILL ADDRESS EACH 28 00:01:08,507 --> 00:01:10,242 AREA, AND THROUGHOUT THE DAY 29 00:01:10,242 --> 00:01:12,711 THERE WILL BE PANEL DISCUSSIONS 30 00:01:12,711 --> 00:01:23,255 TO ALLOW FOR EXCHANGE OF IDEAS. 31 00:01:24,790 --> 00:01:30,329 I'LL NOW TURN IT BACK TO DR. 32 00:01:30,329 --> 00:01:32,631 AGRI WAL. 33 00:01:32,631 --> 00:01:34,900 >> I'M THE PROGRAM DIRECTOR, AND 34 00:01:34,900 --> 00:01:36,935 ON BEHALF OF THE ORGANIZING 35 00:01:36,935 --> 00:01:38,537 COMMITTEE IT'S MY GREAT PLEASURE 36 00:01:38,537 --> 00:01:42,708 TO WELCOME YOU TO THIS NHLBI 37 00:01:42,708 --> 00:01:43,342 SEPSIS WORKSHOP. 38 00:01:43,342 --> 00:01:48,280 THE PURPOSE IS TO BRING TOGETHER 39 00:01:48,280 --> 00:01:49,381 EXPERTS AND STAKEHOLDERS TO 40 00:01:49,381 --> 00:01:51,884 DISCUSS DEVELOPMENTS AND GAPS IN 41 00:01:51,884 --> 00:01:54,720 UNDERSTANDING AND MANAGING 42 00:01:54,720 --> 00:01:54,953 SEPSIS. 43 00:01:54,953 --> 00:01:56,054 WE HAVE ABOUT 200 PARTICIPANTS 44 00:01:56,054 --> 00:02:00,959 WHO HAVE REGISTERED FOR THIS 45 00:02:00,959 --> 00:02:01,927 WORKSHOP, FROM 155 46 00:02:01,927 --> 00:02:02,561 ORGANIZATIONS, WHICH REFLECTS 47 00:02:02,561 --> 00:02:04,796 THE BROAD INTEREST IN THE GLOBAL 48 00:02:04,796 --> 00:02:09,468 HEALTH CHALLENGE. 49 00:02:09,468 --> 00:02:10,068 NEXT SLIDE. 50 00:02:10,068 --> 00:02:14,439 FIRST I WOULD LIKE TO EXTEND 51 00:02:14,439 --> 00:02:16,074 THANKS TO CO-CHAIRS AND 52 00:02:16,074 --> 00:02:17,609 MODERATORS FOR DEDICATION AND 53 00:02:17,609 --> 00:02:18,377 CONTRIBUTIONS OVER SEVERAL 54 00:02:18,377 --> 00:02:21,546 MONTHS, WHICH HAS MADE THIS 55 00:02:21,546 --> 00:02:22,547 EVENT POSSIBLE. 56 00:02:22,547 --> 00:02:25,817 THANK YOU. 57 00:02:25,817 --> 00:02:26,585 NEXT SLIDE. 58 00:02:26,585 --> 00:02:31,623 I WOULD ALSO LIKE TO THANK MY 59 00:02:31,623 --> 00:02:32,925 NHLBI CO-CHAIR FOR HIS INTEGRAL 60 00:02:32,925 --> 00:02:37,963 ROLE IN THE ORGANIZATION OF THIS 61 00:02:37,963 --> 00:02:39,398 WORKSHOP AND OUR NHLBI COLLEAGUE 62 00:02:39,398 --> 00:02:42,000 WHO CO-CHAIRED THE PLANNING OF 63 00:02:42,000 --> 00:02:44,102 THIS WORKSHOP, NOW AT NCI. 64 00:02:44,102 --> 00:02:46,939 FINALLY A SPECIAL THANKS TO THE 65 00:02:46,939 --> 00:02:48,774 ENTIRE WORKSHOP COORDINATING 66 00:02:48,774 --> 00:02:53,745 TEAM THAT WORKED BEHIND THE 67 00:02:53,745 --> 00:03:02,387 SCENES IN ENSURING LOGISTICS. 68 00:03:02,387 --> 00:03:02,587 NEXT. 69 00:03:02,587 --> 00:03:05,991 WHILE THE FIELD OF SEPSIS IS 70 00:03:05,991 --> 00:03:07,192 QUITE BROAD, THIS WORKSHOP HAS 71 00:03:07,192 --> 00:03:09,695 BEEN DIVIDED INTO THREE 72 00:03:09,695 --> 00:03:11,530 SESSIONS, AS DR. PANEPINTO 73 00:03:11,530 --> 00:03:12,431 MENTIONED, EACH EXPLORATION A 74 00:03:12,431 --> 00:03:15,000 CRITICAL AND EMERGING AREA OF 75 00:03:15,000 --> 00:03:16,969 SEPSIS RESEARCH. 76 00:03:16,969 --> 00:03:19,137 THE FIRST WILL EXPLORE 77 00:03:19,137 --> 00:03:21,974 DISPARITIES IN SEPSIS, AN ISSUE 78 00:03:21,974 --> 00:03:23,642 THAT DISPROPORTIONATELY AFFECTS 79 00:03:23,642 --> 00:03:25,477 VULNERABLE POPULATIONS, 80 00:03:25,477 --> 00:03:29,014 UNDERSTANDING THE ROOT CAUSES 81 00:03:29,014 --> 00:03:39,491 AND INFLAWNS -- INFLUENCES. 82 00:03:46,999 --> 00:03:49,134 WE'LL DISCUSS NOVEL MECHANISMS, 83 00:03:49,134 --> 00:03:51,336 EXAMINING HOW IMMUNE SYSTEM 84 00:03:51,336 --> 00:03:53,505 CONTRIBUTES TO SEPSIS 85 00:03:53,505 --> 00:03:55,140 PROGRESSION, IDENTIFYING THERAPY 86 00:03:55,140 --> 00:04:05,650 TARGETS IS A KEY, THIS SESSION 87 00:04:12,257 --> 00:04:16,728 WILL BE BY DR. SUND. 88 00:04:16,728 --> 00:04:27,272 TECHNOLOGIES ARE FOR A PROMISING 89 00:04:43,388 --> 00:04:46,391 FUTURE FOR PERSONALIZED CARE. 90 00:04:46,391 --> 00:04:48,360 THERE BE PANEL DISCUSSION. 91 00:04:48,360 --> 00:04:49,761 I'M CONFIDENT THAT THE 92 00:04:49,761 --> 00:05:00,272 DISCUSSIONS TODAY WILL INSPIRE 93 00:05:08,447 --> 00:05:09,047 NEW IDEAS. 94 00:05:09,047 --> 00:05:16,354 >> WE'RE EXCITED TO HOST THIS 95 00:05:16,354 --> 00:05:16,588 SESSION. 96 00:05:16,588 --> 00:05:18,090 WE'LL COVERED ARRAY OF 97 00:05:18,090 --> 00:05:19,524 DISPARITIES AND IMPACT ON 98 00:05:19,524 --> 00:05:22,494 OUTCOMES AND TOUCH ON MECHANISMS 99 00:05:22,494 --> 00:05:23,728 AS A SEPSIS DISPARITIES AND END 100 00:05:23,728 --> 00:05:26,131 WITH WAYS TO ADDRESS THESE 101 00:05:26,131 --> 00:05:26,431 DISPARITIES. 102 00:05:26,431 --> 00:05:28,767 SO WITH THAT I'D LIKE TO 103 00:05:28,767 --> 00:05:30,802 INTRODUCE OUR FIRST SPEAKER, DR. 104 00:05:30,802 --> 00:05:33,171 CHRISTINA RUDD FROM UNIVERSITY 105 00:05:33,171 --> 00:05:34,906 OF PITTSBURGH, WHO WILL SPEAK 106 00:05:34,906 --> 00:05:36,441 ABOUT THE INFLUENCE OF 107 00:05:36,441 --> 00:05:42,347 COMORBIDITIES ON SEPSIS 108 00:05:42,347 --> 00:05:47,986 INCIDENCE AND OUTCOMES. 109 00:05:47,986 --> 00:05:48,987 >> GOOD MORNING. 110 00:05:48,987 --> 00:05:59,397 THANK YOU FOR HAVING ME. 111 00:06:00,365 --> 00:06:04,002 I'M GOING TO LEAD OFF BY TALKING 112 00:06:04,002 --> 00:06:04,970 ABOUT SEPSIS EPIDEMIOLOGY, 113 00:06:04,970 --> 00:06:06,538 WORLDWIDE, PARTICULARLY IN THE 114 00:06:06,538 --> 00:06:10,275 UNITED STATES, AND THIS REALLY 115 00:06:10,275 --> 00:06:12,244 IMPORTANT ROLE OF COMORBIDITIES, 116 00:06:12,244 --> 00:06:13,211 PARTICULARLY CLUSTERING OF 117 00:06:13,211 --> 00:06:14,546 MULTIPLE COMORBIDITIES IN ONE 118 00:06:14,546 --> 00:06:16,948 INDIVIDUAL, WHICH IS CALLED 119 00:06:16,948 --> 00:06:17,582 MULTI-MORBIDITY. 120 00:06:17,582 --> 00:06:18,583 AND WHAT IMPACT THAT MIGHT HAVE 121 00:06:18,583 --> 00:06:22,287 WHEN WE THINK ABOUT SEPSIS 122 00:06:22,287 --> 00:06:26,858 DISPARITIES IN INCIDENCE AND 123 00:06:26,858 --> 00:06:27,125 OUTCOMES. 124 00:06:27,125 --> 00:06:28,860 NEXT SLIDE PLEASE. 125 00:06:28,860 --> 00:06:31,830 SO, WE KNOW THAT WORK THAT I 126 00:06:31,830 --> 00:06:33,565 HAD -- FROM WORK I DID WITH 127 00:06:33,565 --> 00:06:36,334 COLLEAGUES AROUND THE WORLD 128 00:06:36,334 --> 00:06:37,869 SEVERAL YEARS AGO, WE KNOW 129 00:06:37,869 --> 00:06:42,474 SEPSIS IS A MASSIVE PROBLEM ON A 130 00:06:42,474 --> 00:06:44,409 GLOBAL SCHOOL WITH 50 MILLION 131 00:06:44,409 --> 00:06:48,780 INCIDENT CASES EACH YEAR, 11 132 00:06:48,780 --> 00:06:49,681 MILLION SEPSIS-RELATED DEATHS. 133 00:06:49,681 --> 00:06:51,416 WE KNOW IT'S A BIG PROBLEM, WHAT 134 00:06:51,416 --> 00:06:52,984 ARE WE GOING TO DO ABOUT IT? 135 00:06:52,984 --> 00:06:56,588 WHAT WE FIRST DID IS DRILLED 136 00:06:56,588 --> 00:06:59,958 DOWN ON WHAT'S CAUSING THESE 137 00:06:59,958 --> 00:07:01,059 SEPSIS CASES AND SEPSIS-RELATED 138 00:07:01,059 --> 00:07:03,261 DEATHS, WHAT WE MIGHT BE ABLE TO 139 00:07:03,261 --> 00:07:04,663 DO ONES WE CAN LEARN FROM THAT. 140 00:07:04,663 --> 00:07:05,764 NEXT SLIDE PLEASE. 141 00:07:05,764 --> 00:07:09,367 WHAT WE FIRST DID IS WE 142 00:07:09,367 --> 00:07:14,839 CATEGORIZED THESE DEATHS 143 00:07:14,839 --> 00:07:16,575 ACCORDING TO THE DEATH 144 00:07:16,575 --> 00:07:17,576 CERTIFICATE WHEN THEY DIED, WHAT 145 00:07:17,576 --> 00:07:19,244 THEY PUT AS THE IMMEDIATE CAUSE 146 00:07:19,244 --> 00:07:20,645 OF DEATH ON THE DEATH 147 00:07:20,645 --> 00:07:22,380 CERTIFICATE WAS ALWAYS SEPSIS OR 148 00:07:22,380 --> 00:07:24,482 SEPTIC SHOCK, BUT IN MANY, MANY 149 00:07:24,482 --> 00:07:26,384 OF THESE CASES THE TREATING 150 00:07:26,384 --> 00:07:27,986 CLINICIANS PUT ALL THEIR THINGS 151 00:07:27,986 --> 00:07:32,023 ON THERE THAT IMMEDIATELY LED TO 152 00:07:32,023 --> 00:07:34,526 THIS SEPSIS-RELATED DEATH. 153 00:07:34,526 --> 00:07:35,327 WE FIRST BINNED THOSE ACCORDING 154 00:07:35,327 --> 00:07:37,829 TO WHETHER IT WAS PURELY AN 155 00:07:37,829 --> 00:07:39,130 ACUTE INFECTION THAT'S IN RED 156 00:07:39,130 --> 00:07:40,565 HERE, OR WHETHER THERE WAS 157 00:07:40,565 --> 00:07:42,968 SOMETHING ELSE THAT LED TO THAT 158 00:07:42,968 --> 00:07:44,169 ACUTE INFECTION LIKE AN INJURY 159 00:07:44,169 --> 00:07:47,439 IN YELLOW OR IN BLUE A 160 00:07:47,439 --> 00:07:48,974 NON-COMMUNICABLE CHRONIC DISEASE 161 00:07:48,974 --> 00:07:51,810 LIKE CIRRHOSIS THAT LED TO 162 00:07:51,810 --> 00:07:58,283 SPONTANEOUS PER PERITONITIS OR 163 00:07:58,283 --> 00:07:59,684 STROKE THAT LED TO PNEUMONIA. 164 00:07:59,684 --> 00:08:02,887 AS HE MOVE FROM LOW 165 00:08:02,887 --> 00:08:04,189 SOCIODEMOGRAPHIC ON THE LEFT, ON 166 00:08:04,189 --> 00:08:06,925 THE X-AXIS, TO HIGH SDI ON THE 167 00:08:06,925 --> 00:08:08,026 RIGHT HAND WHERE THE UNITED 168 00:08:08,026 --> 00:08:10,862 STATES SITS YOU CAN SEE AT LEAST 169 00:08:10,862 --> 00:08:12,931 HALF OF SEPSIS-RELATED DEATHS 170 00:08:12,931 --> 00:08:14,466 WORLDWIDE HAVE SOMETHING OTHER 171 00:08:14,466 --> 00:08:16,434 THAN JUST AN ACUTE INFECTION 172 00:08:16,434 --> 00:08:17,535 THAT LED TO THAT SEPSIS DEATH. 173 00:08:17,535 --> 00:08:20,272 AND IN THE U.S. IT'S WELL OVER 174 00:08:20,272 --> 00:08:22,807 50% OF THOSE DEATHS HAD A 175 00:08:22,807 --> 00:08:24,776 NON-COMMUNICABLE CONDITION. 176 00:08:24,776 --> 00:08:26,311 WE CAN ALREADY SEE AT HIGH LEVEL 177 00:08:26,311 --> 00:08:31,750 THERE'S SOMETHING GOING ON HERE. 178 00:08:31,750 --> 00:08:32,751 NEXT SLIDE PLEASE. 179 00:08:32,751 --> 00:08:36,321 WE DUG DOWN FURTHER AND 180 00:08:36,321 --> 00:08:37,756 CATEGORIZED CAUSES AMONG 282 181 00:08:37,756 --> 00:08:39,324 CAUSES, AND LOOKED TO SEE WHAT 182 00:08:39,324 --> 00:08:40,425 ROSE TO THE TOP. 183 00:08:40,425 --> 00:08:43,161 SO WHAT'S LISTED HERE IS THE TOP 184 00:08:43,161 --> 00:08:45,664 20 UNDERLYING CAUSES OF 185 00:08:45,664 --> 00:08:46,298 SEPSIS-RELATED DEATHS AT THREE 186 00:08:46,298 --> 00:08:47,766 TIME POINTS. 187 00:08:47,766 --> 00:08:51,870 ON THE LEFT 1990, MIDDLE IS 188 00:08:51,870 --> 00:08:53,872 2007, RIGHT IS 2017. 189 00:08:53,872 --> 00:08:56,941 MOSTLY I WANT TO DRAW YOUR EYES 190 00:08:56,941 --> 00:08:59,911 TO THE COLOR HERE. 191 00:08:59,911 --> 00:09:02,681 SO, AMONG THE TOP 20 UNDERLYING 192 00:09:02,681 --> 00:09:05,083 CAUSES OF DEATH, PINK IS WHERE 193 00:09:05,083 --> 00:09:08,987 IT WAS INFECTION LISTED AS 194 00:09:08,987 --> 00:09:11,089 UNDERLYING CAUSE, BUT PURPLE IS 195 00:09:11,089 --> 00:09:12,724 A NON-INFECTIOUS CONDITION THAT 196 00:09:12,724 --> 00:09:15,126 LED TO THAT ACUTE INFECTION. 197 00:09:15,126 --> 00:09:17,529 AGAIN, HERE YOU CAN SEE IN THE 198 00:09:17,529 --> 00:09:21,599 TOP 20 YEAR ON YEAR ARE THINGS 199 00:09:21,599 --> 00:09:23,568 LIKE STROKE, CIRRHOSIS, COPD, 200 00:09:23,568 --> 00:09:24,102 DIABETES, CHRONIC KIDNEY 201 00:09:24,102 --> 00:09:27,305 DISEASE, THAT YOU'LL HEAR MORE 202 00:09:27,305 --> 00:09:29,774 ABOUT LATER THIS MORNING. 203 00:09:29,774 --> 00:09:31,109 NEXT SLIDE PLEASE. 204 00:09:31,109 --> 00:09:32,544 WELL, WHAT ABOUT IN THE UNITED 205 00:09:32,544 --> 00:09:32,777 STATES? 206 00:09:32,777 --> 00:09:34,446 I'VE ALREADY TOLD YOU WHEN WE 207 00:09:34,446 --> 00:09:35,613 LOOKED GLOBALLY AND DRILLED DOWN 208 00:09:35,613 --> 00:09:39,017 IN THE U.S., AT LEAST HALF OF 209 00:09:39,017 --> 00:09:39,617 SEPSIS-RELATED DEATHS LOOKED 210 00:09:39,617 --> 00:09:42,087 LIKE THEY WERE RELATED TO A 211 00:09:42,087 --> 00:09:44,356 CHRONIC CONDITION, AND INDEED 212 00:09:44,356 --> 00:09:46,791 AMONG THE 190,000 DEATHS THAT 213 00:09:46,791 --> 00:09:48,560 ARE ESTIMATED TO BE DUE TO 214 00:09:48,560 --> 00:09:51,730 SEPSIS IN THE UNITED STATES EACH 215 00:09:51,730 --> 00:09:55,100 YEAR, AS OF 2017, THE NEXT SLIDE 216 00:09:55,100 --> 00:09:57,302 PLEASE SHOWS THAT 58% OF THESE 217 00:09:57,302 --> 00:09:59,938 DEATHS ARE ASSOCIATED WITH AN 218 00:09:59,938 --> 00:10:00,672 UNDERLYING NON-COMMUNICABLE 219 00:10:00,672 --> 00:10:01,072 DISEASE. 220 00:10:01,072 --> 00:10:03,074 AGAIN, THESE ARE NOT JUST PEOPLE 221 00:10:03,074 --> 00:10:04,709 THAT HAVE A CHRONIC DISEASE, 222 00:10:04,709 --> 00:10:07,812 THESE ARE CASES WHERE THAT 223 00:10:07,812 --> 00:10:08,913 TREATING CLINICIAN WHO WITNESSED 224 00:10:08,913 --> 00:10:11,549 THE STAFF FELT THIS 225 00:10:11,549 --> 00:10:12,984 NON-COMMUNICABLE CONDITION, THE 226 00:10:12,984 --> 00:10:14,152 CHRONIC DISEASE DIRECTLY LED TO 227 00:10:14,152 --> 00:10:18,757 THIS INCIDENCE OF SEPSIS 228 00:10:18,757 --> 00:10:20,291 ULTIMATELY TOOK SOMEBODY'S LIFE. 229 00:10:20,291 --> 00:10:22,160 NEXT SLIDE PLEASE. 230 00:10:22,160 --> 00:10:24,863 SO, WE SEE THIS PATTERN 231 00:10:24,863 --> 00:10:25,864 REPLICATED IN THE LITERATURE FAR 232 00:10:25,864 --> 00:10:27,732 BEYOND WHAT WE DID WITH THE 233 00:10:27,732 --> 00:10:30,034 GLOBAL BURDEN OF DISEASE 234 00:10:30,034 --> 00:10:32,637 PROJECT. 235 00:10:32,637 --> 00:10:34,072 SO THIS PAPER PUBLISHED LAST 236 00:10:34,072 --> 00:10:37,342 YEAR WAS A SCOPING REVIEW OF 237 00:10:37,342 --> 00:10:39,110 OVER 100 ARTICLES, ALL FOCUSED 238 00:10:39,110 --> 00:10:41,946 ON THE UNITED STATES, AND THEY 239 00:10:41,946 --> 00:10:45,784 SET OUT TO EXAMINE THE 240 00:10:45,784 --> 00:10:47,852 RELATIONSHIP BETWEEN SEPSIS 241 00:10:47,852 --> 00:10:49,287 INCIDENCE AND MORTALITY, AND 242 00:10:49,287 --> 00:10:50,155 SOCIOECONOMIC DISADVANTAGE. 243 00:10:50,155 --> 00:10:52,056 WHAT THEY ENDED UP FINDING IS 244 00:10:52,056 --> 00:10:55,894 THAT THERE WAS THIS REALLY 245 00:10:55,894 --> 00:10:57,962 IMPORTANT COMPONENT OF CHRONIC 246 00:10:57,962 --> 00:11:00,799 DISEASE THAT FIT INTO THIS 247 00:11:00,799 --> 00:11:02,233 RELATIONSHIP BETWEEN SEPSIS AND 248 00:11:02,233 --> 00:11:02,567 DISPARITIES. 249 00:11:02,567 --> 00:11:04,736 WHAT THEY FOUND IS THAT 250 00:11:04,736 --> 00:11:07,071 CONSISTENTLY IN PAPER AFTER 251 00:11:07,071 --> 00:11:09,474 PAPER, IN THE SCOPING REVIEW, 252 00:11:09,474 --> 00:11:12,310 THAT AUTHORS WERE FINDING A 253 00:11:12,310 --> 00:11:13,511 RELATIONSHIP WITH THIS 254 00:11:13,511 --> 00:11:15,146 CLUSTERING OF SEPSIS INCIDENCE 255 00:11:15,146 --> 00:11:17,015 AND MORTALITY OR ASSOCIATED 256 00:11:17,015 --> 00:11:19,117 COMPLICATIONS OF SEPSIS IN 257 00:11:19,117 --> 00:11:21,186 NEIGHBORHOODS WITH HIGH 258 00:11:21,186 --> 00:11:21,753 SOCIOECONOMIC DISADVANTAGE, 259 00:11:21,753 --> 00:11:24,989 SIGNIFICANT POVERTY, AT THE SAME 260 00:11:24,989 --> 00:11:26,991 TIME PAPERS WERE REPORTING 261 00:11:26,991 --> 00:11:28,426 CLUSTERING OF CHRONIC 262 00:11:28,426 --> 00:11:31,162 HYPERTENSION AND DIABETES, IN 263 00:11:31,162 --> 00:11:33,231 THE EXACT SAME GEOGRAPHIC 264 00:11:33,231 --> 00:11:36,267 DISTRIBUTION, SUGGESTING MAYBE 265 00:11:36,267 --> 00:11:36,935 THIS POTENTIAL SHARED 266 00:11:36,935 --> 00:11:38,470 PATHOPHYSIOLOGY LINK. 267 00:11:38,470 --> 00:11:40,972 WHAT THE AUTHORS ARE DEPICTING 268 00:11:40,972 --> 00:11:42,307 IN THIS FIGURE HERE IS 269 00:11:42,307 --> 00:11:44,175 HYPOTHESIS BASED ON THEIR 270 00:11:44,175 --> 00:11:47,212 FINDINGS OF THE SCOPING REVIEW 271 00:11:47,212 --> 00:11:53,785 THAT PERHAPS THERE'S SOME 272 00:11:53,785 --> 00:11:55,520 PHYSIOLOGIC LEAN BETWEEN THE RED 273 00:11:55,520 --> 00:11:57,956 STAR ON TOP HERE AND SEPSIS DOWN 274 00:11:57,956 --> 00:12:02,327 IN THE BOTTOM RIGHT CORNER, AND 275 00:12:02,327 --> 00:12:04,729 HYPOTHESIZED THAT VIA 276 00:12:04,729 --> 00:12:07,232 ENVIRONMENTAL TRIGGERS AND I 277 00:12:07,232 --> 00:12:10,301 WOULD SAY I CONCEIVE OF 278 00:12:10,301 --> 00:12:11,603 ENVIRONMENT BROADLY WE'RE NOT 279 00:12:11,603 --> 00:12:14,472 JUST THINKING ABOUT AIR 280 00:12:14,472 --> 00:12:15,840 POLLUTION, I'M SEEING NOT 281 00:12:15,840 --> 00:12:16,074 AUDIBLE. 282 00:12:16,074 --> 00:12:17,675 LET ME PAUSE AND MAKE SURE 283 00:12:17,675 --> 00:12:20,612 EVERYONE CAN HEAR ME. 284 00:12:20,612 --> 00:12:23,348 >> WE ALL CAN HEAR YOU. 285 00:12:23,348 --> 00:12:23,681 >> GREAT. 286 00:12:23,681 --> 00:12:25,416 THANK YOU. 287 00:12:25,416 --> 00:12:25,984 OKAY. 288 00:12:25,984 --> 00:12:28,152 SO, THEY PROPOSED THAT THESE 289 00:12:28,152 --> 00:12:30,788 ENVIRONMENTAL TRIGGERS WERE 290 00:12:30,788 --> 00:12:31,756 LEADING TO ENDOTHELIAL 291 00:12:31,756 --> 00:12:33,091 DYSFUNCTION, WHICH WE'LL HEAR 292 00:12:33,091 --> 00:12:35,827 ABOUT LATER TODAY, AND THIS 293 00:12:35,827 --> 00:12:37,462 DYSFUNCTION IS A SHARED FEATURE 294 00:12:37,462 --> 00:12:39,531 OF THESE CHRONIC DISEASES THAT 295 00:12:39,531 --> 00:12:41,499 WE SEE SHOWING UP CLUSTERING IN 296 00:12:41,499 --> 00:12:43,401 THESE NEIGHBORHOODS WITH STRONG 297 00:12:43,401 --> 00:12:44,969 SOCIOECONOMIC DISADVANTAGE, AND 298 00:12:44,969 --> 00:12:49,374 WE SEE IT AS I'VE JUST SHOWN 299 00:12:49,374 --> 00:12:50,475 CLUSTERING AMONG ACCEPT 300 00:12:50,475 --> 00:12:51,676 'TIS-RELATED DEATHS AND MAYBE 301 00:12:51,676 --> 00:12:56,381 THERE'S A LINK THROUGH THE 302 00:12:56,381 --> 00:12:57,181 ENDOTHELIUM. 303 00:12:57,181 --> 00:12:58,883 IT'S NOT JUST THESE SINGLE 304 00:12:58,883 --> 00:13:03,288 COMORBIDITIES IN ISOLATION BUT 305 00:13:03,288 --> 00:13:04,055 IT'S ACCUMULATION OF 306 00:13:04,055 --> 00:13:06,658 COMORBIDITIES IN IN A SINGLE 307 00:13:06,658 --> 00:13:07,659 INDIVIDUAL THAT PUTS THEM AT 308 00:13:07,659 --> 00:13:09,627 RISK TO DEVELOP AND DIE FROM 309 00:13:09,627 --> 00:13:10,161 SEPSIS. 310 00:13:10,161 --> 00:13:12,564 THIS IS A REALLY NEAT PAPER THAT 311 00:13:12,564 --> 00:13:15,533 WAS PUBLISHED SEVERAL YEARS AGO, 312 00:13:15,533 --> 00:13:18,469 I THINK STILL RELEVANT, DR. BECK 313 00:13:18,469 --> 00:13:20,138 AND COLLEAGUES TOOK ELECTRONIC 314 00:13:20,138 --> 00:13:22,740 HEALTH RECORD DATA IN DENMARK 315 00:13:22,740 --> 00:13:24,375 COVERING ALL HOSPITAL ENCOUNTERS 316 00:13:24,375 --> 00:13:26,277 OVER 18-YEAR TIME PERIOD ACROSS 317 00:13:26,277 --> 00:13:27,345 THE COUNTRY, OVER 6 MILLION 318 00:13:27,345 --> 00:13:28,012 PATIENTS. 319 00:13:28,012 --> 00:13:31,883 AND THEY FOUND THAT IN THE 30 320 00:13:31,883 --> 00:13:34,485 DAYS BEFORE SOMEBODY WROTE CODE 321 00:13:34,485 --> 00:13:37,522 A-41, ICD CODE ON THE FAR RIGHT 322 00:13:37,522 --> 00:13:40,959 OF THE SLIDE HERE, OTHER 323 00:13:40,959 --> 00:13:42,694 SEPTICEMIA, INDICATING SOMEBODY 324 00:13:42,694 --> 00:13:44,929 DIED FROM SEPSIS, CODE A41, BACK 325 00:13:44,929 --> 00:13:47,265 30 DAYS TO SEE WHAT OTHER ICD 326 00:13:47,265 --> 00:13:48,900 CODES HAD SOMEBODY WRITTEN IN 327 00:13:48,900 --> 00:13:50,768 THIS PERSON'S CHART IN THE 328 00:13:50,768 --> 00:13:52,637 PRECEDING 30 DAYS. 329 00:13:52,637 --> 00:13:55,740 AND WHAT THEY FOUND WAS THESE 330 00:13:55,740 --> 00:13:58,476 RECURRENT TRAJECTORIES OF TIME 331 00:13:58,476 --> 00:14:00,445 ORDERED ACCUMULATION OF CERTAIN 332 00:14:00,445 --> 00:14:02,513 COMORBIDITIES ASSOCIATED WITH 333 00:14:02,513 --> 00:14:03,381 SIGNIFICANTLY INCREASED SEPSIS 334 00:14:03,381 --> 00:14:06,017 MORTALITY COMPARED TO PEOPLE WHO 335 00:14:06,017 --> 00:14:07,452 DIDN'T FOLLOW THOSE TIME-ORDERED 336 00:14:07,452 --> 00:14:07,785 TRAJECTORIES. 337 00:14:07,785 --> 00:14:10,188 AND I WANT TO DRAW YOUR EYES TO 338 00:14:10,188 --> 00:14:12,924 SOME OF THESE BIGGER NODES, 339 00:14:12,924 --> 00:14:14,459 PARTICULARLY THE STARTING NODES 340 00:14:14,459 --> 00:14:17,929 ON THE LEFT-HAND SIDE OF THE 341 00:14:17,929 --> 00:14:19,464 SLIDE, DIABETES, ACUTE CORONARY 342 00:14:19,464 --> 00:14:20,665 SYNDROME, HYPERTENSION AGAIN, 343 00:14:20,665 --> 00:14:23,201 ALCOHOL USE DISORDER SHOWING UP 344 00:14:23,201 --> 00:14:24,936 HERE AS REALLY SIGNIFICANT 345 00:14:24,936 --> 00:14:27,672 STARTING POINTS IN THOSE 30 DAYS 346 00:14:27,672 --> 00:14:33,144 PRECEDING SEPSIS-RELATED DEATH. 347 00:14:33,144 --> 00:14:33,811 NEXT SLIDE PLEASE. 348 00:14:33,811 --> 00:14:35,446 OTHERS LOOKED IN THE UNITED 349 00:14:35,446 --> 00:14:37,548 STATES AND REPLICATED SIMILAR 350 00:14:37,548 --> 00:14:38,483 FINDINGS. 351 00:14:38,483 --> 00:14:40,385 THIS STUDY USED THE MIMIC 352 00:14:40,385 --> 00:14:41,619 DATASET WHICH DRAWS FROM 40,000 353 00:14:41,619 --> 00:14:45,990 PATIENTS IN THE UNITED STATES, 354 00:14:45,990 --> 00:14:47,592 PEOPLE ADMITTED TO CRITICAL 355 00:14:47,592 --> 00:14:49,460 CARE, INTENSIVE CARE UNITS. 356 00:14:49,460 --> 00:14:53,097 AND THEY WANTED TO SEE IF THERE 357 00:14:53,097 --> 00:14:53,765 WERE CERTAIN IDENTIFIABLE 358 00:14:53,765 --> 00:14:55,166 SUBGROUPS OF PATIENTS THAT MIGHT 359 00:14:55,166 --> 00:14:57,035 BE ASSOCIATED WITH INCREASED 360 00:14:57,035 --> 00:14:58,236 RISK FOR SEPSIS, IS WHAT THEY 361 00:14:58,236 --> 00:14:59,537 SET OUT TO DO. 362 00:14:59,537 --> 00:15:03,141 SO FIRST THEY USED LATENT CLASS 363 00:15:03,141 --> 00:15:04,475 ANALYSIS TO IDENTIFY DISTINCT 364 00:15:04,475 --> 00:15:06,544 SIX PATIENT SUBGROUPS. 365 00:15:06,544 --> 00:15:08,846 AND WHAT THEY FOUND IS THAT 366 00:15:08,846 --> 00:15:12,784 THESE SIX SUBGROUPS ON THIS LEFT 367 00:15:12,784 --> 00:15:14,552 FIGURE LISTED ACROSS THE BOTTOM 368 00:15:14,552 --> 00:15:17,388 REALLY VARIED IN THE NUMBER OF 369 00:15:17,388 --> 00:15:18,256 COMORBIDITIES THAT INDIVIDUALS 370 00:15:18,256 --> 00:15:21,526 IN THAT GROUP HAD, AND THEY 371 00:15:21,526 --> 00:15:22,527 FOUND THESE GROUPS PARTICULARLY 372 00:15:22,527 --> 00:15:26,030 GROUPS 1, 3, AND 4, THAT HAD 373 00:15:26,030 --> 00:15:26,798 REALLY HIGH MULTI-MORBIDITY 374 00:15:26,798 --> 00:15:27,231 COUNTS. 375 00:15:27,231 --> 00:15:29,534 THESE ARE PEOPLE IN THESE GROUPS 376 00:15:29,534 --> 00:15:33,037 THAT HAVE FIVE, SIX, SEVEN, 377 00:15:33,037 --> 00:15:33,604 SOMETIMES OVER EIGHT 378 00:15:33,604 --> 00:15:36,107 COMORBIDITIES, AND THEY COULD 379 00:15:36,107 --> 00:15:37,308 SEE THAT CLUSTERING BY 380 00:15:37,308 --> 00:15:37,642 COMORBIDITY. 381 00:15:37,642 --> 00:15:40,178 FOR THE GROUPS WITH HIGH 382 00:15:40,178 --> 00:15:41,279 MULTI-MORBIDITY COUNTS, GROUPS 383 00:15:41,279 --> 00:15:43,114 1, 3, AND 4, I WANTED TO SHOW 384 00:15:43,114 --> 00:15:44,348 SOME COMORBIDITIES THAT ARE 385 00:15:44,348 --> 00:15:46,284 SHOWING UP THERE. 386 00:15:46,284 --> 00:15:50,221 AGAIN, YOU CAN SEE IN THE TOP 387 00:15:50,221 --> 00:15:51,355 SUBGROUP 1 HYPERTENSION, 388 00:15:51,355 --> 00:15:53,257 CONGESTIVE HEART FAILURE, IN THE 389 00:15:53,257 --> 00:15:54,492 BOTTOM RIGHT SUBGROUP 4 390 00:15:54,492 --> 00:15:56,360 HYPERTENSION AGAIN, THERE IT IS 391 00:15:56,360 --> 00:15:59,997 WITH DIABETES, AND THE LEFT YOU 392 00:15:59,997 --> 00:16:01,866 CAN SEE ALCOHOL USE, OTHER 393 00:16:01,866 --> 00:16:02,533 SUBSTANCE USE, CLUSTERING WITH 394 00:16:02,533 --> 00:16:03,301 LIVER DISEASE. 395 00:16:03,301 --> 00:16:06,471 SO THEN WHAT THEY DID ON THE 396 00:16:06,471 --> 00:16:08,873 NEXT SLIDE PLEASE IS ONCE THEY 397 00:16:08,873 --> 00:16:11,609 IDENTIFIED SIX SUBGROUPS THEY 398 00:16:11,609 --> 00:16:14,579 TESTED WHETHER MEMBERSHIP IN ONE 399 00:16:14,579 --> 00:16:15,980 OF THESE LATENT SUBGROUPS MIGHT 400 00:16:15,980 --> 00:16:18,082 BE ASSOCIATED WITH RISK FOR 401 00:16:18,082 --> 00:16:20,384 BEING ADMITTED TO ICU WITH ORGAN 402 00:16:20,384 --> 00:16:22,019 DYSFUNCTION OR SEPSIS, THAT'S 403 00:16:22,019 --> 00:16:29,427 THIS PREVALENT GRAPH ON THE 404 00:16:29,427 --> 00:16:30,328 LEFT, OR ULTIMATELY DYING, THE 405 00:16:30,328 --> 00:16:32,730 GRAPH ON THE RIGHT. 406 00:16:32,730 --> 00:16:34,932 SUBGROUPS 1, 3, AND 4 WITH HIGH 407 00:16:34,932 --> 00:16:35,700 LEVELS OF MULTI-MORBIDITY ARE 408 00:16:35,700 --> 00:16:38,770 ALSO THE SUBGROUPS THAT HAVE THE 409 00:16:38,770 --> 00:16:40,738 HIGHEST PERCENT PREVALENCE OF 410 00:16:40,738 --> 00:16:42,707 ORGAN DYSFUNCTION IN SEPSIS, 411 00:16:42,707 --> 00:16:45,777 OTHER THAN SUBGROUP 6, WHICH IS 412 00:16:45,777 --> 00:16:47,311 PATIENTS WITH ADVANCED 413 00:16:47,311 --> 00:16:48,412 CONGESTIVE HEART FAILURE, ON THE 414 00:16:48,412 --> 00:16:50,047 RIGHT THOSE PATIENTS HAD HIGH 415 00:16:50,047 --> 00:16:50,815 MORTALITY. 416 00:16:50,815 --> 00:16:53,651 BUT MY TAKEAWAY HERE IS THAT 417 00:16:53,651 --> 00:16:55,620 MULTI-MORBIDITY IS STRONGLY 418 00:16:55,620 --> 00:16:56,587 ASSOCIATED WITH SEPSIS AND ORGAN 419 00:16:56,587 --> 00:16:58,456 DYSFUNCTION AND PEOPLE IN THE 420 00:16:58,456 --> 00:17:00,558 UNITED STATES ARE DYING FROM 421 00:17:00,558 --> 00:17:02,426 THIS KIND OF CLUSTERING. 422 00:17:02,426 --> 00:17:03,961 NEXT SLIDE PLEASE. 423 00:17:03,961 --> 00:17:07,632 SO, TO SUMMARIZE THIS FIRST KIND 424 00:17:07,632 --> 00:17:10,968 OF MAIN POINTS OF MY TALK I HOPE 425 00:17:10,968 --> 00:17:13,905 YOU CAN SEE THAT COMORBIDITIES, 426 00:17:13,905 --> 00:17:21,579 PARTICULARLY CLUSTERING IS A 427 00:17:21,579 --> 00:17:23,114 STRONG RISK FACTOR. 428 00:17:23,114 --> 00:17:24,982 SOME CONDITIONS AT HIGHEST RISK 429 00:17:24,982 --> 00:17:29,987 ARE ALCOHOL AND OTHER SUBSTANCE 430 00:17:29,987 --> 00:17:33,090 USE, CIRRHOSIS, DIABETES, 431 00:17:33,090 --> 00:17:37,829 HYPERTENSION, CUMULATIVE BURDEN, 432 00:17:37,829 --> 00:17:39,263 PARTICULARLY ACCUMULATED IN 433 00:17:39,263 --> 00:17:39,897 TEMPORAL DISTRIBUTION IS 434 00:17:39,897 --> 00:17:43,801 IMPORTANT AND RISK OF 435 00:17:43,801 --> 00:17:45,436 MULTI-MORBIDITY HAS BEEN 436 00:17:45,436 --> 00:17:52,443 DEMONSTRATED ACROSS POPULATIONS, 437 00:17:52,443 --> 00:17:55,046 AGES, SETTINGS, RESEARCH 438 00:17:55,046 --> 00:17:55,646 THOUGHTS. 439 00:17:55,646 --> 00:17:59,750 LESS WELL KNOWN WITH BETTER 440 00:17:59,750 --> 00:18:01,319 APPROACHES AND MITIGATE. 441 00:18:01,319 --> 00:18:02,954 I'M GOING TO USE LITERATURE TO 442 00:18:02,954 --> 00:18:06,324 PROPOSE A COUPLE IDEAS TO GET US 443 00:18:06,324 --> 00:18:09,293 STARTED IN OUR CONVERSATIONS. 444 00:18:09,293 --> 00:18:12,697 SO IDEA ONE IS WHAT IF WE COULD 445 00:18:12,697 --> 00:18:14,031 USE INNOVATEIVE RESEARCH METHODS 446 00:18:14,031 --> 00:18:19,270 TO BETTER UNDERSTAND WHAT 447 00:18:19,270 --> 00:18:20,571 MULTI-MORBIDITY, IS THIS 448 00:18:20,571 --> 00:18:21,939 BIOLOGIC RISK THROUGH 449 00:18:21,939 --> 00:18:22,607 ENDOTHELIAL DYSFUNCTION OR 450 00:18:22,607 --> 00:18:25,309 DYSREGULATION OF THE IMMUNE 451 00:18:25,309 --> 00:18:25,610 SYSTEM? 452 00:18:25,610 --> 00:18:27,511 OR ARE THERE OTHER INDIVIDUAL 453 00:18:27,511 --> 00:18:28,846 LEVEL RISKS LIKE SOCIAL 454 00:18:28,846 --> 00:18:31,349 DETERMINANTS OF HEALTH, 455 00:18:31,349 --> 00:18:33,618 COMMUNITY LEVEL EXPOSURES, EVEN 456 00:18:33,618 --> 00:18:36,587 SYSTEMIC EXPOSURES THAT MIGHT 457 00:18:36,587 --> 00:18:38,656 HAVE SYNDEMIC RELATIONSHIP OR 458 00:18:38,656 --> 00:18:39,757 CLUSTERING WITH MULTI-MORBIDITY 459 00:18:39,757 --> 00:18:40,691 AND SEPSIS TOGETHER. 460 00:18:40,691 --> 00:18:42,293 THIS IS AN APPROACH I'M TAKING 461 00:18:42,293 --> 00:18:45,897 CURRENTLY USING A GRANT FROM THE 462 00:18:45,897 --> 00:18:47,198 NIH USING HIERARCHICAL MODELING 463 00:18:47,198 --> 00:18:48,833 APPROACHES AND INTEGRATION OF 464 00:18:48,833 --> 00:18:50,167 HEALTH RECORDS AND POPULATION 465 00:18:50,167 --> 00:18:53,337 LEVEL DATA TO FURTHER UNPACK AND 466 00:18:53,337 --> 00:18:55,640 TEASE APART THIS POTENTIAL 467 00:18:55,640 --> 00:18:57,808 SYNDEMIC RELATIONSHIP BETWEEN 468 00:18:57,808 --> 00:19:01,846 MULTI-MORBIDITY AND SEPSIS. 469 00:19:01,846 --> 00:19:03,080 NEXT SLIDE. 470 00:19:03,080 --> 00:19:06,250 IN ADDITION TO DESCRIBING 471 00:19:06,250 --> 00:19:07,218 CLUSTERING OF RISK FACTORS WE 472 00:19:07,218 --> 00:19:08,953 NEED TO UNDERSTAND MORE ABOUT 473 00:19:08,953 --> 00:19:11,255 THE WHY AND HOW. 474 00:19:11,255 --> 00:19:12,156 I THINK EPIGENETIC RESEARCH 475 00:19:12,156 --> 00:19:15,126 WHICH I DO NOT DO BUT AM A BIG 476 00:19:15,126 --> 00:19:18,396 FAN OF IN TERMS OF CONSUMER 477 00:19:18,396 --> 00:19:19,931 LITERATURE, I THINK THIS IS ONE 478 00:19:19,931 --> 00:19:21,666 REALLY INTERESTING AND IMPORTANT 479 00:19:21,666 --> 00:19:24,936 WAY TO FURTHER UNPACK THESE 480 00:19:24,936 --> 00:19:25,269 RELATIONSHIPS. 481 00:19:25,269 --> 00:19:26,804 THIS IS ONE ARTICLE PUBLISHED 482 00:19:26,804 --> 00:19:29,340 EARLIER THIS SUMMER FROM AN 483 00:19:29,340 --> 00:19:30,741 INNOVATIVE SET OF STUDIES 484 00:19:30,741 --> 00:19:33,277 PUBLISHED TOGETHER IN JULY IN 485 00:19:33,277 --> 00:19:38,549 JAMA NETWORK OPEN FROM THE NIMHD 486 00:19:38,549 --> 00:19:39,750 SOCIAL EPIGENOMICS PROGRAM. 487 00:19:39,750 --> 00:19:42,253 AND I WANTED TO SHOW THIS AS AN 488 00:19:42,253 --> 00:19:44,021 EXAMPLE OF THE INCREDIBLE WORK 489 00:19:44,021 --> 00:19:46,357 THAT'S BEING FUNDED BY THE NIH, 490 00:19:46,357 --> 00:19:48,960 PERFORMED ACROSS THE UNITED 491 00:19:48,960 --> 00:19:50,928 STATES, TRYING TO UNDERSTAND THE 492 00:19:50,928 --> 00:19:53,164 ROLE OF EPIGENETICS IN HEALTH, 493 00:19:53,164 --> 00:19:58,836 AND PARTICULARLY IN HEALTH 494 00:19:58,836 --> 00:20:00,338 DISPARITIES. 495 00:20:00,338 --> 00:20:05,843 THIS PAPER'S SPECIFIC OBJECTIVE 496 00:20:05,843 --> 00:20:10,014 TO EVALUATE WHETHER ACCELERATED 497 00:20:10,014 --> 00:20:12,383 EPIGENETIC AGING IS RELATED 498 00:20:12,383 --> 00:20:13,217 AMONG U.S.-BORN INDIVIDUALS IN 499 00:20:13,217 --> 00:20:14,352 SEVERAL STATES. 500 00:20:14,352 --> 00:20:15,886 NEXT SLIDE PLEASE. 501 00:20:15,886 --> 00:20:17,088 >> TWO MINUTES REMAINING. 502 00:20:17,088 --> 00:20:19,156 THANK YOU. 503 00:20:19,156 --> 00:20:19,824 >> PERFECT, THANK YOU. 504 00:20:19,824 --> 00:20:22,026 ANOTHER IDEA IN TERMS OF WHAT WE 505 00:20:22,026 --> 00:20:24,862 MIGHT DO TO FURTHER UNDERSTAND 506 00:20:24,862 --> 00:20:28,499 THIS RELATIONSHIP BETWEEN 507 00:20:28,499 --> 00:20:31,002 MULTI-MORBIDITY AND SEPSIS IS 508 00:20:31,002 --> 00:20:32,570 THINK ABOUT USING THESE TOOLS TO 509 00:20:32,570 --> 00:20:34,772 IDENTIFY THOSE PEOPLE AT HIGHEST 510 00:20:34,772 --> 00:20:37,708 RISK, THESE PEOPLE WITH MULTIPLE 511 00:20:37,708 --> 00:20:38,909 COMORBIDITIES, THAT ARE 512 00:20:38,909 --> 00:20:40,644 CLUSTERING AND ACCUMULATING OVER 513 00:20:40,644 --> 00:20:41,879 TIME. 514 00:20:41,879 --> 00:20:43,180 WE KNOW CERTAIN HIGH-RISK 515 00:20:43,180 --> 00:20:44,548 CONDITIONS, ONCE WE CAN IDENTIFY 516 00:20:44,548 --> 00:20:46,350 THOSE INDIVIDUALS WHAT WE DO TO 517 00:20:46,350 --> 00:20:47,118 PROTECT THEM? 518 00:20:47,118 --> 00:20:48,552 ONE OF THE STRONGEST TOOLS WE 519 00:20:48,552 --> 00:20:51,188 HAVE TO PROTECT THEM IS 520 00:20:51,188 --> 00:20:51,455 VACCINES. 521 00:20:51,455 --> 00:20:53,958 WE KNOW FROM THIS TRIAL 522 00:20:53,958 --> 00:20:58,229 PUBLISHED SEVERAL YEARS AGO THAT 523 00:20:58,229 --> 00:21:00,965 TESTED POLYSACCHARIDE VACCINE 524 00:21:00,965 --> 00:21:02,066 AGAINST PNEUMOCOCCAL VACCINE IN 525 00:21:02,066 --> 00:21:03,501 ADULTS THAT VACCINES WORK TO 526 00:21:03,501 --> 00:21:04,568 PREVENT SEPSIS. 527 00:21:04,568 --> 00:21:07,538 YOU SEE THIS IN THE RIGHT PANEL 528 00:21:07,538 --> 00:21:10,074 THAT THE VACCINE PREVENTS 529 00:21:10,074 --> 00:21:12,143 INVASIVE PNEUMOCOCCAL DISEASE. 530 00:21:12,143 --> 00:21:14,445 ON THE NEXT SLIDE, IS AN EXAMPLE 531 00:21:14,445 --> 00:21:17,148 OF A TRIAL THAT TAKES THAT 532 00:21:17,148 --> 00:21:19,116 EVIDENCE OF KNOWING VACCINES 533 00:21:19,116 --> 00:21:23,054 WORK AND HELPS US PUSH FORWARD 534 00:21:23,054 --> 00:21:25,723 HOW CAN WE BETTER PROTECT PEOPLE 535 00:21:25,723 --> 00:21:31,028 WHO ARE AT RISK OF SEPSIS AND 536 00:21:31,028 --> 00:21:32,029 WHO ARE UNDERVACCINATED, WHETHER 537 00:21:32,029 --> 00:21:34,765 THEY ARE AT RISK DUE TO SOCIAL 538 00:21:34,765 --> 00:21:38,803 RISK FACTORS, OR MEDICAL RISK 539 00:21:38,803 --> 00:21:40,571 FACTORS, OR BOTH. 540 00:21:40,571 --> 00:21:42,773 IN THIS A SLIDE TO THINK ABOUT 541 00:21:42,773 --> 00:21:43,741 INNOVATIVE TRIAL DESIGN AND 542 00:21:43,741 --> 00:21:48,879 THINKING HOW TO PROMOTE VACCINE 543 00:21:48,879 --> 00:21:49,113 UPTAKE. 544 00:21:49,113 --> 00:21:49,413 NEXT SLIDE. 545 00:21:49,413 --> 00:21:50,414 THIS IS YET ANOTHER IDEA OF WHAT 546 00:21:50,414 --> 00:21:52,149 WE MIGHT DO ABOUT THIS. 547 00:21:52,149 --> 00:21:54,685 WHAT IF WE IDENTIFIED THOSE 548 00:21:54,685 --> 00:21:55,653 PATIENTS WITH MULTI-MORBIDITY WE 549 00:21:55,653 --> 00:21:59,924 THINK ARE AT RISK AND GIVE THEM 550 00:21:59,924 --> 00:22:02,860 EDUCATION, MAYBE WEARABLE 551 00:22:02,860 --> 00:22:10,234 DEVICES, IN-HOME ASSAYS, 24-HOUR 552 00:22:10,234 --> 00:22:11,802 NURSE LINES TO REDUCE SEPSIS 553 00:22:11,802 --> 00:22:12,870 EARLY, THERE'S MAJOR CHALLENGES 554 00:22:12,870 --> 00:22:14,371 IN INEQUITY I HOPE WE'LL TALK 555 00:22:14,371 --> 00:22:16,040 ABOUT TODAY BUT THIS IS 556 00:22:16,040 --> 00:22:17,575 PROMISING PARTICULARLY IN THE 557 00:22:17,575 --> 00:22:24,115 SESSION ON A.I. LATER ON TODAY. 558 00:22:24,115 --> 00:22:24,482 NEXT SLIDE. 559 00:22:24,482 --> 00:22:26,217 SO THIS SUMMARIZES FUTURE 560 00:22:26,217 --> 00:22:26,650 DIRECTIONS. 561 00:22:26,650 --> 00:22:29,487 I THINK THAT WE REALLY NEED MORE 562 00:22:29,487 --> 00:22:32,690 EFFECTIVENESS AS WELL AS 563 00:22:32,690 --> 00:22:34,325 IMPLEMENTATION RESEARCH FOCUSING 564 00:22:34,325 --> 00:22:35,659 ON REDUCES SEPSIS INCIDENCE AND 565 00:22:35,659 --> 00:22:38,496 MORTALITY AMONG PEOPLE WITH 566 00:22:38,496 --> 00:22:39,463 COMORBIDITIES, ESPECIALLY 567 00:22:39,463 --> 00:22:40,564 MULTI-MORBIDITIES AND PROPOSED 568 00:22:40,564 --> 00:22:41,465 SOME IDEAS ON INTERVENTIONS THAT 569 00:22:41,465 --> 00:22:43,868 COULD RANGE FROM THOSE THAT 570 00:22:43,868 --> 00:22:45,736 REDUCED IMPACT OF COMORBIDITIES 571 00:22:45,736 --> 00:22:48,139 TO IMPROVING CONTROL OF 572 00:22:48,139 --> 00:22:50,241 COMORBIDITIES, PREVENTING 573 00:22:50,241 --> 00:22:53,043 INFECTION, OR EVEN IDENTIFYING 574 00:22:53,043 --> 00:22:54,778 EARLIER TREATING SEPSIS TO 575 00:22:54,778 --> 00:22:55,112 REDUCE DELAYS. 576 00:22:55,112 --> 00:22:57,314 AND FINALLY I THINK THAT 577 00:22:57,314 --> 00:23:00,718 ACCOUNTING FOR THAT 578 00:23:00,718 --> 00:23:01,252 INTERSECTIONALITY BETWEEN 579 00:23:01,252 --> 00:23:02,586 MEDICAL AND SOCIAL RISK IS 580 00:23:02,586 --> 00:23:03,921 CRITICAL AND LOOK FORWARD TO 581 00:23:03,921 --> 00:23:05,890 CONVERSATION ABOUT THAT. 582 00:23:05,890 --> 00:23:08,025 NEXT SLIDE IS JUST I THANK YOU 583 00:23:08,025 --> 00:23:13,631 FOR INVITING ME TO SPEAK. 584 00:23:13,631 --> 00:23:15,833 >> THANK YOU, DR. RUDD. 585 00:23:15,833 --> 00:23:17,902 THAT WAS FANTASTIC. 586 00:23:17,902 --> 00:23:19,670 I'LL OPEN UP TO QUESTIONS FROM 587 00:23:19,670 --> 00:23:21,839 THE AUDIENCE, ASK A QUESTION OR 588 00:23:21,839 --> 00:23:24,275 PLACE THE QUESTION IN THE CHAT 589 00:23:24,275 --> 00:23:29,446 IF THERE'S QUESTIONS FOR DR. 590 00:23:29,446 --> 00:23:29,747 RUDD. 591 00:23:29,747 --> 00:23:31,749 WE WILL HAVE A DISCUSSION ABOUT 592 00:23:31,749 --> 00:23:33,384 ALL OF THE TALKS IN THIS SESSION 593 00:23:33,384 --> 00:23:35,352 AT THE END, SO WE'LL RESERVE 594 00:23:35,352 --> 00:23:37,988 DISCUSSION FOR THE END. 595 00:23:37,988 --> 00:23:39,490 BUT IF THERE'S A PARTICULAR 596 00:23:39,490 --> 00:23:42,860 QUESTION FOR DR. RUDD PLEASE 597 00:23:42,860 --> 00:23:48,699 FEEL FREE TO ASK THE QUESTIONS. 598 00:23:48,699 --> 00:23:59,310 >> GO AHEAD, YOU HAVE A QUESTIO. 599 00:24:01,345 --> 00:24:08,986 >> DR. ASHANA HAS A QUESTION? 600 00:24:08,986 --> 00:24:18,229 >> WE CAN'T HEAR YOU. 601 00:24:18,229 --> 00:24:21,332 >> SHE DIDN'T HAVE A QUESTION. 602 00:24:21,332 --> 00:24:21,865 OKAY. 603 00:24:21,865 --> 00:24:24,068 SO, WE'LL GO AHEAD AND MOVE ON 604 00:24:24,068 --> 00:24:25,035 THEN AND -- 605 00:24:25,035 --> 00:24:26,904 >> CAN I ASK A QUESTION BEFORE 606 00:24:26,904 --> 00:24:28,339 WE MOVE ON? 607 00:24:28,339 --> 00:24:29,640 >> YES, OF COURSE. 608 00:24:29,640 --> 00:24:32,943 >> DR. RUDD, SINCE YOU MENTIONED 609 00:24:32,943 --> 00:24:38,482 ENDOTHELIAL DYSFUNCTION, I WAS 610 00:24:38,482 --> 00:24:39,583 WONDERING IF NEUTROPHIL INVASION 611 00:24:39,583 --> 00:24:44,088 INTO THE SITES OF INFECTION IS 612 00:24:44,088 --> 00:24:47,925 ONE OF THE CAUSES FOR INCREASED 613 00:24:47,925 --> 00:24:49,560 INFECTION BECAUSE OF ENDOTHELIAL 614 00:24:49,560 --> 00:24:49,860 DYSFUNCTION. 615 00:24:49,860 --> 00:24:52,529 I KNOW THIS QUESTION WILL COME 616 00:24:52,529 --> 00:24:56,967 UP LATER ON IN OTHER TALKS ALSO 617 00:24:56,967 --> 00:24:59,036 BUT SINCE YOU MENTIONED IT -- 618 00:24:59,036 --> 00:25:00,704 >> GREAT QUESTION. 619 00:25:00,704 --> 00:25:03,240 I WILL ADMIT THAT IT'S OUTSIDE 620 00:25:03,240 --> 00:25:06,210 MY PRIMARY AREA OF EXPERTISE BUT 621 00:25:06,210 --> 00:25:11,348 WILL SAY THERE ARE A LOT OF 622 00:25:11,348 --> 00:25:12,249 INTERESTING HYPOTHESES AROUND 623 00:25:12,249 --> 00:25:14,084 THIS RELATIONSHIP BETWEEN WHICH 624 00:25:14,084 --> 00:25:14,718 COMORBIDITIES ARE REALLY RISING 625 00:25:14,718 --> 00:25:22,092 TO THE TOP IN TERMS OF STRONG 626 00:25:22,092 --> 00:25:22,660 ASSOCIATION WITH SEPSIS AND 627 00:25:22,660 --> 00:25:24,395 MORTALITY, AND I'M INTERESTED IN 628 00:25:24,395 --> 00:25:26,563 KNOWING WHAT IS HAPPENING 629 00:25:26,563 --> 00:25:28,666 CHRONICALLY IN THE IMMUNE SYSTEM 630 00:25:28,666 --> 00:25:31,068 OF FOLKS THAT ARE ACCUMULATING 631 00:25:31,068 --> 00:25:32,136 COMORBIDITIES, PARTICULARLY 632 00:25:32,136 --> 00:25:33,470 THINGS LIKE DIABETES, CHRONIC 633 00:25:33,470 --> 00:25:37,408 KIDNEY DISEASE, HYPERTENSION 634 00:25:37,408 --> 00:25:45,816 THAT SHARE VASCULAR 635 00:25:45,816 --> 00:25:46,917 PATHOPHYSIOLOGY AND HOW THAT 636 00:25:46,917 --> 00:25:48,786 MIGHT PUT PEOPLE AT RISK ONCE 637 00:25:48,786 --> 00:25:50,087 THEY DEVELOP INFECTION, SO I 638 00:25:50,087 --> 00:25:51,655 THINK IT'S A GREAT QUESTION. 639 00:25:51,655 --> 00:25:55,025 >> THANK YOU. 640 00:25:55,025 --> 00:26:00,164 >> ANY OTHER QUESTIONS FOR DR. 641 00:26:00,164 --> 00:26:02,900 RUDD? 642 00:26:02,900 --> 00:26:04,101 >> I HAVE A QUESTION. 643 00:26:04,101 --> 00:26:08,806 WHAT CAN YOU DO ABOUT ALCOHOL 644 00:26:08,806 --> 00:26:11,208 USE DISORDERS, IS THERE ANYTHING 645 00:26:11,208 --> 00:26:12,910 PREVENTIVE CAN YOU DO? 646 00:26:12,910 --> 00:26:14,745 >> YEAH, THAT'S A REALLY 647 00:26:14,745 --> 00:26:15,913 IMPORTANT QUESTION. 648 00:26:15,913 --> 00:26:20,217 I THINK AS -- WHEN I THINK ABOUT 649 00:26:20,217 --> 00:26:20,884 MULTI-MORBIDITY OR THESE 650 00:26:20,884 --> 00:26:23,187 COMORBIDITIES THAT SEEM TO BE 651 00:26:23,187 --> 00:26:25,889 STRONGLY ASSOCIATED WITH SEPSIS, 652 00:26:25,889 --> 00:26:28,892 I THINK ABOUT PREVENTION OR 653 00:26:28,892 --> 00:26:30,194 REDUCING RISK ALONG THE 654 00:26:30,194 --> 00:26:30,561 SPECTRUM. 655 00:26:30,561 --> 00:26:32,963 WE'LL TALK ABOUT IT LATER ON 656 00:26:32,963 --> 00:26:38,168 WITH DR. ES PER AND DR. ASHANA 657 00:26:38,168 --> 00:26:39,503 AS WELL BUT PREVENTING 658 00:26:39,503 --> 00:26:40,504 COMORBIDITIES OR TREATING THEM 659 00:26:40,504 --> 00:26:42,039 WELL ONCE THEY DEVELOP IS 660 00:26:42,039 --> 00:26:42,873 ABSOLUTELY ESSENTIAL BECAUSE IF 661 00:26:42,873 --> 00:26:45,943 WE WAIT TO THE END AND JUST 662 00:26:45,943 --> 00:26:46,844 REDUCE, YOU KNOW, DELAY GETTING 663 00:26:46,844 --> 00:26:48,979 TO THE HOSPITAL ONCE YOU HAVE 664 00:26:48,979 --> 00:26:50,114 SEPSIS WE'RE WAY TOO LATE AND WE 665 00:26:50,114 --> 00:26:52,182 DON'T HAVE A LOT TO CHANGE 666 00:26:52,182 --> 00:26:55,152 OUTCOME AT THAT POINT OTHER THAN 667 00:26:55,152 --> 00:26:55,919 ANTIBIOTICS. 668 00:26:55,919 --> 00:26:57,654 SO, ABSOLUTELY THERE ARE 669 00:26:57,654 --> 00:26:59,623 EFFECTIVE TREATMENTS, I'D SAY 670 00:26:59,623 --> 00:27:00,958 MULTI-MODAL TREATMENTS VALUE FOR 671 00:27:00,958 --> 00:27:03,460 ALCOHOL USE AND OTHER SUBSTANCE 672 00:27:03,460 --> 00:27:05,462 USE DISORDERS, THAT ONCE 673 00:27:05,462 --> 00:27:08,532 SOMEBODY HAS DEVELOPED THOSE, 674 00:27:08,532 --> 00:27:11,802 PLUGGING PEOPLE INTO APPROPRIATE 675 00:27:11,802 --> 00:27:14,071 CARE HOLISTIC WHOLE-PERSON CARE, 676 00:27:14,071 --> 00:27:15,072 I THINK CAN ABSOLUTELY REDUCE 677 00:27:15,072 --> 00:27:16,273 THEIR RISK. 678 00:27:16,273 --> 00:27:17,975 THAT I WILL ADMIT IS MY 679 00:27:17,975 --> 00:27:18,275 HYPOTHESIS. 680 00:27:18,275 --> 00:27:20,344 I THINK WE DON'T HAVE THE DATA 681 00:27:20,344 --> 00:27:22,846 YET, AND WE NEED THE DATA TO 682 00:27:22,846 --> 00:27:26,383 TELL US WHAT DOES HAPPEN IF WE 683 00:27:26,383 --> 00:27:27,351 TREAT THESE COMORBIDITIES WELL 684 00:27:27,351 --> 00:27:28,685 IN TERMS OF PREVENTING SEPSIS 685 00:27:28,685 --> 00:27:35,325 DOWN THE ROAD. 686 00:27:35,325 --> 00:27:36,093 >> CAN YOU HEAR ME NOW? 687 00:27:36,093 --> 00:27:39,496 >> DO YOU HAVE A QUESTION? 688 00:27:39,496 --> 00:27:41,565 >> THANKS FOR A FANTASTIC TALK. 689 00:27:41,565 --> 00:27:45,736 ONE QUESTION FOR YOU IS CURRENT 690 00:27:45,736 --> 00:27:46,703 SEPSIS TREATMENT IS ONE SIZE 691 00:27:46,703 --> 00:27:48,372 FITS ALL, I WONDER OF SOME OF 692 00:27:48,372 --> 00:27:50,641 WHAT YOU'RE PROPOSING THERE MAY 693 00:27:50,641 --> 00:27:51,742 BE DIFFERENT PHENOTYPES WHICH 694 00:27:51,742 --> 00:27:53,043 PEOPLE HAVE ALREADY STARTED TO 695 00:27:53,043 --> 00:27:55,345 PARSE OUT A BIT, AND IS THERE 696 00:27:55,345 --> 00:27:56,780 POTENTIALLY DOWN THE LINE A 697 00:27:56,780 --> 00:27:58,081 DIFFERENT SORT OF TREATMENT THAT 698 00:27:58,081 --> 00:27:59,516 MIGHT BE NEEDED FOR FOLKS WHO 699 00:27:59,516 --> 00:28:01,952 ARE SHOWING UP WITH 700 00:28:01,952 --> 00:28:03,620 MULTI-MORBIDITY AND A LOT OF 701 00:28:03,620 --> 00:28:06,890 SOCIAL RISK FACTORS AS WELL? 702 00:28:06,890 --> 00:28:08,859 >> YEAH, I THINK THAT'S A GREAT 703 00:28:08,859 --> 00:28:09,193 POINT. 704 00:28:09,193 --> 00:28:10,694 ABSOLUTELY, I DO THINK THAT 705 00:28:10,694 --> 00:28:13,530 THERE ARE MULTIPLE PHENOTYPES OF 706 00:28:13,530 --> 00:28:13,964 SEPSIS. 707 00:28:13,964 --> 00:28:15,399 DR. SEYMOUR AND OTHERS HAVE DONE 708 00:28:15,399 --> 00:28:17,401 NIGHT WORK IN THAT SPACE. 709 00:28:17,401 --> 00:28:18,902 AND THEY HAVE -- MOST OF THE 710 00:28:18,902 --> 00:28:22,072 WORK I'M AWARE OF HAS PRIMARILY 711 00:28:22,072 --> 00:28:23,373 FOCUSED ON THE ORGAN DYSFUNCTION 712 00:28:23,373 --> 00:28:25,375 THAT'S PRESENT AT THE TIME THAT 713 00:28:25,375 --> 00:28:28,178 PATIENT IS IDENTIFIED AND 714 00:28:28,178 --> 00:28:28,645 ADMITTED WITH SEPSIS. 715 00:28:28,645 --> 00:28:31,482 RATHER THAN LOOKING AT THE ORGAN 716 00:28:31,482 --> 00:28:32,916 DYSFUNCTION THAT'S PRESENT IN 717 00:28:32,916 --> 00:28:35,118 THE DAYS, WEEKS, MONTHS, YEARS 718 00:28:35,118 --> 00:28:35,853 PRIOR TO THAT. 719 00:28:35,853 --> 00:28:39,356 AND SO I GUESS WHEN I THINK 720 00:28:39,356 --> 00:28:40,390 ABOUT SEPSIS TREATMENT, AGAIN, I 721 00:28:40,390 --> 00:28:43,093 TEND TO THINK IN A MORE HOLISTIC 722 00:28:43,093 --> 00:28:44,728 PUBLIC HEALTH PERSPECTIVE WHICH 723 00:28:44,728 --> 00:28:47,030 IS, YES, FOR SURE, THERE 724 00:28:47,030 --> 00:28:48,232 PROBABLY ARE DIFFERENCES IN 725 00:28:48,232 --> 00:28:50,767 TREATMENT OF THAT ACUTE EPISODE 726 00:28:50,767 --> 00:28:52,970 OF SEPSIS BUT THERE ARE PROBABLY 727 00:28:52,970 --> 00:28:54,271 REALLY IMPORTANT DIFFERENCES IN 728 00:28:54,271 --> 00:28:56,773 HOW WE'RE GOING TO PREVENT 729 00:28:56,773 --> 00:28:57,875 SEPSIS, DEPENDING ON DIFFERENT 730 00:28:57,875 --> 00:28:59,510 PEOPLE'S RISK FACTORS, AND THEN 731 00:28:59,510 --> 00:29:02,045 ALSO HOW WE'RE GOING TO PREVENT 732 00:29:02,045 --> 00:29:03,780 READMISSION WITH SEPSIS, WHICH 733 00:29:03,780 --> 00:29:05,983 WE KNOW IS COMMON AFTER PEOPLE 734 00:29:05,983 --> 00:29:07,384 HAVE BEEN HOSPITALIZED WITH 735 00:29:07,384 --> 00:29:09,486 SEPSIS, AND I'M EXCITED TO HEAR 736 00:29:09,486 --> 00:29:10,687 PEOPLE'S THOUGHTS IN THE 737 00:29:10,687 --> 00:29:12,990 WORKSHOP TODAY ABOUT HOW WE 738 00:29:12,990 --> 00:29:15,692 MIGHT USE INNOVATIVE RESEARCH 739 00:29:15,692 --> 00:29:17,794 APPROACHES, TECHNOLOGIES, TO 740 00:29:17,794 --> 00:29:19,763 PERSONALIZE THAT ACCORDING TO 741 00:29:19,763 --> 00:29:21,732 THE PRESENCE OF MEDICAL AS WELL 742 00:29:21,732 --> 00:29:32,142 AS SOCIAL RISK FACTORS. 743 00:29:32,976 --> 00:29:34,177 >> THANK YOU, DR. RUDD. 744 00:29:34,177 --> 00:29:34,945 >> THANK YOU. 745 00:29:34,945 --> 00:29:37,514 >> WE'RE GOING TO MOVE ON TO OUR 746 00:29:37,514 --> 00:29:39,349 NEXT TALK, I'D LIKE TO INTRODUCE 747 00:29:39,349 --> 00:29:43,053 DR. GREG MARTIN FROM EMORY 748 00:29:43,053 --> 00:29:43,620 UNIVERSITY, DISCUSSING MORE 749 00:29:43,620 --> 00:29:44,955 SPECIFICS ABOUT COMORBIDITIES 750 00:29:44,955 --> 00:29:50,827 AND IMPACT ON HEALTH 751 00:29:50,827 --> 00:29:51,528 DISPARITIES. 752 00:29:51,528 --> 00:29:54,765 >> THANK YOU, DR. ESPER. 753 00:29:54,765 --> 00:29:57,734 I APPRECIATE THE OPPORTUNITY, A 754 00:29:57,734 --> 00:29:58,368 TERRIFIC WORKSHOP, APPRECIATIVE 755 00:29:58,368 --> 00:30:00,237 OF THE CHANCE TO PARTICIPATE AND 756 00:30:00,237 --> 00:30:01,438 LEARN FROM EVERYONE HERE. 757 00:30:01,438 --> 00:30:04,174 SO I'M GOING TO SHARE MORE ABOUT 758 00:30:04,174 --> 00:30:05,042 COMORBIDITIES AND 759 00:30:05,042 --> 00:30:06,476 MULTI-MORBIDITY AND WHAT I'LL 760 00:30:06,476 --> 00:30:09,212 SHARE REALLY WILL COMPLEMENT 761 00:30:09,212 --> 00:30:11,148 WHAT KRISTINA RUDD JUST 762 00:30:11,148 --> 00:30:12,182 DESCRIBED, THINKING PARTICULARLY 763 00:30:12,182 --> 00:30:14,484 WHERE THESE FIT TOGETHER WITH 764 00:30:14,484 --> 00:30:15,552 THE DIFFERENT COMORBIDITIES AND 765 00:30:15,552 --> 00:30:17,421 DISPARITIES THAT WE SEE IN 766 00:30:17,421 --> 00:30:18,388 HEALTH INEQUITIES AND HOW THOSE 767 00:30:18,388 --> 00:30:23,260 PLAY TOGETHER. 768 00:30:23,260 --> 00:30:24,928 NEXT SLIDE. 769 00:30:24,928 --> 00:30:26,930 I DON'T HAVE ANY CONFLICTS OF 770 00:30:26,930 --> 00:30:27,197 INTEREST. 771 00:30:27,197 --> 00:30:28,899 I'VE WORKED IN SEVERAL AREAS 772 00:30:28,899 --> 00:30:29,766 RELATED TO SPACES. 773 00:30:29,766 --> 00:30:31,501 GO AHEAD TO THE NEXT SLIDE. 774 00:30:31,501 --> 00:30:33,604 I WILL JUST TOUCH ON THE FACT 775 00:30:33,604 --> 00:30:35,339 THAT SEPSIS IS VERY, VERY 776 00:30:35,339 --> 00:30:36,039 IMPORTANT, AS CHRISTINA 777 00:30:36,039 --> 00:30:37,741 MENTIONED IT'S ONE OF THE MOST 778 00:30:37,741 --> 00:30:39,409 COMMON DISEASES IN THE WORLD, 779 00:30:39,409 --> 00:30:40,711 ALSO THE NUMBER THREE LEADING 780 00:30:40,711 --> 00:30:42,579 CAUSE OF DEATH IN THE UNITED 781 00:30:42,579 --> 00:30:42,813 STATES. 782 00:30:42,813 --> 00:30:43,981 IT ACCOUNTS FOR SUBSTANTIAL 783 00:30:43,981 --> 00:30:46,049 NUMBER OF HOSPITAL DEATHS. 784 00:30:46,049 --> 00:30:46,650 OFTEN IS UNDERESTIMATED 785 00:30:46,650 --> 00:30:47,718 PARTICULARLY IN RELATION TO 786 00:30:47,718 --> 00:30:49,119 OTHER COMMON DISEASES WHERE WE 787 00:30:49,119 --> 00:30:51,321 SEE A LOT OF RESOURCES AND A LOT 788 00:30:51,321 --> 00:30:54,958 OF ATTENTION. 789 00:30:54,958 --> 00:30:55,392 NEXT SLIDE. 790 00:30:55,392 --> 00:30:58,095 I WANT TO FOCUS ON RISK FACTORS, 791 00:30:58,095 --> 00:31:00,964 THINKING ABOUT RISK FACTORS 792 00:31:00,964 --> 00:31:02,699 PARTICULARLY AS THEY RELATE TO 793 00:31:02,699 --> 00:31:03,900 COMORBIDITIES, HEALTH EQUITY, 794 00:31:03,900 --> 00:31:05,869 AND DISPARITIES. 795 00:31:05,869 --> 00:31:06,770 NEXT SLIDE. 796 00:31:06,770 --> 00:31:09,706 SO LET'S START HERE IN THE TOP 797 00:31:09,706 --> 00:31:10,907 RIGHT-HAND CORNER, YOU SEE AGE 798 00:31:10,907 --> 00:31:12,976 AS A RISK FACTOR FOR SEPSIS. 799 00:31:12,976 --> 00:31:13,744 WE'LL TOUCH ON THAT. 800 00:31:13,744 --> 00:31:17,247 ON THE LEFT HAND WHAT YOU SEE IS 801 00:31:17,247 --> 00:31:19,449 THINGS LIKE RACE OR ETHNICITY, 802 00:31:19,449 --> 00:31:22,686 AND GENDER AS RISK FACTORS FOR 803 00:31:22,686 --> 00:31:23,920 SEPSIS, LOWER RIGHT-HAND CORNER 804 00:31:23,920 --> 00:31:25,789 WHAT YOU SEE IS ONE WAY TO THINK 805 00:31:25,789 --> 00:31:26,890 ABOUT THE VARIETY OF 806 00:31:26,890 --> 00:31:28,091 COMORBIDITIES THAT MIGHT COME 807 00:31:28,091 --> 00:31:28,458 TOGETHER. 808 00:31:28,458 --> 00:31:30,927 WHAT I REALLY WANT TO FOCUS ON 809 00:31:30,927 --> 00:31:32,262 IS WHAT UNDERLIES THESE RISK 810 00:31:32,262 --> 00:31:33,997 FACTORS AND HOW DO THEY PLAY OUT 811 00:31:33,997 --> 00:31:38,602 NOT ONLY IN INDIVIDUALS BUT IN 812 00:31:38,602 --> 00:31:38,969 COMMUNITIES. 813 00:31:38,969 --> 00:31:39,803 NEXT SLIDE. 814 00:31:39,803 --> 00:31:41,238 LET'S START WITH GENDER 815 00:31:41,238 --> 00:31:43,106 INFLUENCE IN SEPSIS, THIS IS 816 00:31:43,106 --> 00:31:44,975 DATA WE GENERATED ABOUT 20 YEARS 817 00:31:44,975 --> 00:31:46,810 AGO NOW LOOKING AT SEPSIS 818 00:31:46,810 --> 00:31:48,311 INCIDENCE AND OUTCOME OVER MANY 819 00:31:48,311 --> 00:31:50,881 YEARS IN THE UNITED STATES. 820 00:31:50,881 --> 00:31:53,417 FROM A GENDER PERSPECTIVE WE SAW 821 00:31:53,417 --> 00:31:55,252 MEN WERE 30% MORE LIKELY TO 822 00:31:55,252 --> 00:31:56,620 DEVELOP SEPSIS, REALLY EVERY 823 00:31:56,620 --> 00:31:59,723 YEAR COMPARED TO WOMEN. 824 00:31:59,723 --> 00:32:00,424 NEXT SLIDE. 825 00:32:00,424 --> 00:32:01,525 BUT THERE'S SEVERAL OTHER 826 00:32:01,525 --> 00:32:02,826 ELEMENTS THAT COME TOGETHER 827 00:32:02,826 --> 00:32:04,027 HERE, PARTICULARLY IF YOU'RE 828 00:32:04,027 --> 00:32:05,529 TRYING TO UNDERSTAND THE GENDER 829 00:32:05,529 --> 00:32:07,431 DISPARITIES THAT EXIST IN SEPSIS 830 00:32:07,431 --> 00:32:08,398 INCIDENCE, ONE WAY TO THINK 831 00:32:08,398 --> 00:32:10,267 ABOUT THAT WOULD BE ALSO THEN TO 832 00:32:10,267 --> 00:32:12,102 THINK ABOUT COMORBIDITIES. 833 00:32:12,102 --> 00:32:14,638 IN THIS SLIDE WHAT YOU SEE, THIS 834 00:32:14,638 --> 00:32:21,211 IS DATA GENERATED BY ANNETTE 835 00:32:21,211 --> 00:32:26,016 ESPER, COMORBIDITIES TRACK WITH 836 00:32:26,016 --> 00:32:26,750 GENDER. 837 00:32:26,750 --> 00:32:29,720 THE FIRST TWO ON LEFT, DIABETES, 838 00:32:29,720 --> 00:32:31,321 MEN IN BLUE, WOMEN IN PINK, MEN 839 00:32:31,321 --> 00:32:33,123 ARE MUCH MORE LIKELY TO HAVE 840 00:32:33,123 --> 00:32:33,390 DIABETES. 841 00:32:33,390 --> 00:32:35,325 WE KNOW DIABETES IS A STRONG 842 00:32:35,325 --> 00:32:37,627 RISK FACTOR FOR INFECTION. 843 00:32:37,627 --> 00:32:40,363 WE ALSO HAVE DATA ABOUT DIABETES 844 00:32:40,363 --> 00:32:43,867 AND SEVERAL COMORBIDITIES YOU 845 00:32:43,867 --> 00:32:44,634 ALSO SEE DISPROPORTIONATELY 846 00:32:44,634 --> 00:32:47,137 REPRESENTED IN MEN COMPARED TO 847 00:32:47,137 --> 00:32:49,539 WOMEN, HIV, COPD, CHRONIC KIDNEY 848 00:32:49,539 --> 00:32:51,174 DISEASE, CANCER, ALCOHOLISM, ALL 849 00:32:51,174 --> 00:32:52,709 THOSE PLAY A ROLE AND ARE 850 00:32:52,709 --> 00:32:53,477 DISPROPORTIONATELY REPRESENTED 851 00:32:53,477 --> 00:32:55,779 IN MEN COMPARED TO WOMEN. 852 00:32:55,779 --> 00:32:57,647 THEY MAY WELL UNDERLIE SOME 853 00:32:57,647 --> 00:33:01,585 DIFFERENCES IN SUBSTANCE 854 00:33:01,585 --> 00:33:02,686 INCIDENCE THAT WE SEE. 855 00:33:02,686 --> 00:33:03,420 NEXT SLIDE. 856 00:33:03,420 --> 00:33:04,654 THERE'S OTHER THINGS WE SEE AS 857 00:33:04,654 --> 00:33:04,855 WELL. 858 00:33:04,855 --> 00:33:06,923 FOR INSTANCE, MEN ARE MORE LIKE 859 00:33:06,923 --> 00:33:08,892 THROW HAVE GRAM POSITIVE 860 00:33:08,892 --> 00:33:09,359 INFECTIONS. 861 00:33:09,359 --> 00:33:11,528 YOU MIGHT INTUIT THAT'S RELATED 862 00:33:11,528 --> 00:33:12,529 TO THE COMORBIDITIES, BUT ALSO 863 00:33:12,529 --> 00:33:16,233 MAY BE RELATED TO TYPES OF 864 00:33:16,233 --> 00:33:17,234 INFECTIONS THEY GET. 865 00:33:17,234 --> 00:33:20,737 FOR INSTANCE, IN MEN, MEN ARE 866 00:33:20,737 --> 00:33:28,979 MUCH MORE LIKELY TO DEVELOP 867 00:33:28,979 --> 00:33:29,946 RESPIRATORY INFECTIONS, WOMEN 868 00:33:29,946 --> 00:33:30,547 GENITOURINARY INFECTION, BUT I 869 00:33:30,547 --> 00:33:32,983 WANT TO COME BACK TO THIS. 870 00:33:32,983 --> 00:33:35,252 IT'S NOT AS SIMPLE AS WE'D LIKE 871 00:33:35,252 --> 00:33:38,255 TO THINK IN TERMS OF GENDER 872 00:33:38,255 --> 00:33:39,689 DISPARITIES, TYPES OF 873 00:33:39,689 --> 00:33:40,991 INFECTIONS, EVEN BACTERIA 874 00:33:40,991 --> 00:33:42,292 CAUSING THEM. 875 00:33:42,292 --> 00:33:43,293 NEXT SLIDE. 876 00:33:43,293 --> 00:33:45,128 SO LET'S JUMP FORWARD AND TALK 877 00:33:45,128 --> 00:33:46,463 ABOUT RACIAL DISPARITIES USING 878 00:33:46,463 --> 00:33:52,269 THE SAME DATA WE GENERATED 879 00:33:52,269 --> 00:33:52,969 SEVERAL YEARS AGO. 880 00:33:52,969 --> 00:34:02,646 THIS IS LOOKING AT RACE AND 881 00:34:02,646 --> 00:34:02,913 ETHNICITY. 882 00:34:02,913 --> 00:34:04,714 AFRICAN AMERICANS TWICE AS 883 00:34:04,714 --> 00:34:06,817 LIKELY TO DEVELOP SEPSIS THAN 884 00:34:06,817 --> 00:34:08,351 CAUCASIANS, BUT LOOK AT 885 00:34:08,351 --> 00:34:10,187 COMORBIDITIES DISTRIBUTED BY 886 00:34:10,187 --> 00:34:12,155 RACE, A RATE RATIO OR RISK 887 00:34:12,155 --> 00:34:14,457 RATIO, SO ONE IS REFERENCE 888 00:34:14,457 --> 00:34:21,998 VALUE, ANYTHING ABOVE ONE WOULD 889 00:34:21,998 --> 00:34:23,400 IMPLY DISPROPORTIONATE 890 00:34:23,400 --> 00:34:25,936 REPRESENTATION, HIV IS HIGHER 891 00:34:25,936 --> 00:34:28,972 RISK OR REPRESENTATION IN 892 00:34:28,972 --> 00:34:30,740 PATIENTS WHO ARE SELF-IDENTIFY 893 00:34:30,740 --> 00:34:32,275 OR IDENTIFIED BY HEALTH SYSTEM 894 00:34:32,275 --> 00:34:33,810 AS BLACK, ALSO TRUE FOR OTHER 895 00:34:33,810 --> 00:34:36,980 RACES, BUT THERE'S OTHER 896 00:34:36,980 --> 00:34:38,315 DISEASES INCLUDES DIABETES, 897 00:34:38,315 --> 00:34:39,950 ALCOHOLISM, CHRONIC KIDNEY 898 00:34:39,950 --> 00:34:41,151 DISEASE THAT ARE 899 00:34:41,151 --> 00:34:41,751 DISPROPORTIONATELY REPRESENTED 900 00:34:41,751 --> 00:34:45,622 AND DO TRACK WITH RACE AND 901 00:34:45,622 --> 00:34:45,889 ETHNICITY. 902 00:34:45,889 --> 00:34:46,389 NEXT SLIDE. 903 00:34:46,389 --> 00:34:48,792 I WANTED TO TOUCH ON THE FACT 904 00:34:48,792 --> 00:34:50,093 THERE ARE DIFFERENCES IN 905 00:34:50,093 --> 00:34:51,294 ORGANISMS BUT ALSO DIFFERENCES 906 00:34:51,294 --> 00:34:53,063 IN ORGANISMS WE MIGHT THINK ARE 907 00:34:53,063 --> 00:34:55,699 RELATED TO THE SOURCE OF 908 00:34:55,699 --> 00:34:57,667 INFECTION BUT WHAT YOU SEE HERE 909 00:34:57,667 --> 00:35:00,337 USING THE SAME DATA, YOU SEE 910 00:35:00,337 --> 00:35:02,672 HERE RACE PLOTTED ON THE FAR 911 00:35:02,672 --> 00:35:06,076 AXIS, THE SOURCE OF INFECTION 912 00:35:06,076 --> 00:35:09,679 PLOTTED ON THE X-AXIS IN FRONT, 913 00:35:09,679 --> 00:35:11,982 PROPORTION OF GRAM-POSITIVE 914 00:35:11,982 --> 00:35:12,282 INFECTIONS. 915 00:35:12,282 --> 00:35:13,216 IN THE BACK LEFT-HAND CORNER 916 00:35:13,216 --> 00:35:19,990 BLACKS WHO HAVE RESPIRATORY 917 00:35:19,990 --> 00:35:24,160 INFECTION ARE MORE LIKELY TO 918 00:35:24,160 --> 00:35:25,362 HAVE GRAM POSITIVE INFECTIONS, 919 00:35:25,362 --> 00:35:27,564 WHICH MAY WELL CONNECT THIS MORE 920 00:35:27,564 --> 00:35:29,432 TO THE SOCIAL DETERMINANTS AND 921 00:35:29,432 --> 00:35:30,467 CO-MORBIDITIES THAN SOURCE OF 922 00:35:30,467 --> 00:35:31,501 INFECTION BECAUSE WITHIN THE 923 00:35:31,501 --> 00:35:32,802 SOURCE OF INFECTION THERE'S 924 00:35:32,802 --> 00:35:34,037 STILL A DIFFERENCE IN ORGANISMS 925 00:35:34,037 --> 00:35:36,206 THAT HAS TO BE EXPLAINED BY 926 00:35:36,206 --> 00:35:37,307 OTHER FACTORS. 927 00:35:37,307 --> 00:35:40,477 SO LET'S KEEP JUMPING FORWARD 928 00:35:40,477 --> 00:35:41,044 NOW. 929 00:35:41,044 --> 00:35:42,545 NEXT SLIDE. 930 00:35:42,545 --> 00:35:43,647 WHAT UNDERLIES RACIAL 931 00:35:43,647 --> 00:35:44,848 DISPARITIES SEPSIS INCIDENCE? 932 00:35:44,848 --> 00:35:46,917 SEVERAL PEOPLE TACKLED THIS. 933 00:35:46,917 --> 00:35:48,351 WE'LL HEAR MORE IN THE NEXT 934 00:35:48,351 --> 00:35:50,754 TALKS AND REST OF THE DAY. 935 00:35:50,754 --> 00:35:51,955 BUT SOME SUGGESTED THERE IS 936 00:35:51,955 --> 00:35:56,126 INCREASE IN RISK OF INFECTION, 937 00:35:56,126 --> 00:35:56,993 UNDERLYING INCITING EVENT, THERE 938 00:35:56,993 --> 00:36:01,498 MAY ALSO BE RISK FOR INCREASED 939 00:36:01,498 --> 00:36:02,299 ORGAN DYSFUNCTION, SEPSIS 940 00:36:02,299 --> 00:36:04,200 PHENOTYPE MEANING WHAT HAPPENS 941 00:36:04,200 --> 00:36:05,635 TO PATIENT AS THEY REPRESENT 942 00:36:05,635 --> 00:36:06,970 SEPSIS, IMMUNE DYSFUNCTION THAT 943 00:36:06,970 --> 00:36:08,705 LEADS TO ORGAN DYSFUNCTION 944 00:36:08,705 --> 00:36:09,339 CAUSING SEPSIS. 945 00:36:09,339 --> 00:36:12,108 SO THIS IS DATA AGAIN LOOKING BY 946 00:36:12,108 --> 00:36:13,743 AGE, SHOWING PEOPLE WHO ARE 947 00:36:13,743 --> 00:36:16,079 IDENTIFIED AS BLACK HAVE HIGHER 948 00:36:16,079 --> 00:36:18,248 RISK OF INFECTION, ALSO HIGHER 949 00:36:18,248 --> 00:36:19,249 RISK OF ORGAN DYSFUNCTION, THAT 950 00:36:19,249 --> 00:36:21,751 SEEMS TO BE TRUE EVEN AT THE 951 00:36:21,751 --> 00:36:23,653 EARLIEST STAGES WHICH IMPLIES 952 00:36:23,653 --> 00:36:26,356 MAYBE THERE'S MORE IT TO, MAYBE 953 00:36:26,356 --> 00:36:26,990 SOCIAL DETERMINANTS, MAYBE OTHER 954 00:36:26,990 --> 00:36:30,627 FACTORS AS WELL. 955 00:36:30,627 --> 00:36:31,861 NEXT SLIDE. 956 00:36:31,861 --> 00:36:35,231 JUSTIN MOORE LOOKED AT THIS 957 00:36:35,231 --> 00:36:40,070 WITHIN DIVERSE RESEARCH COHORT, 958 00:36:40,070 --> 00:36:42,772 ACROSS AREAS OF PARTICULARLY 959 00:36:42,772 --> 00:36:43,606 DIVERSE COHORT FOR 960 00:36:43,606 --> 00:36:45,041 CARDIOVASCULAR REASONS, 961 00:36:45,041 --> 00:36:46,276 REPRESENTED ACROSS THE UNITED 962 00:36:46,276 --> 00:36:46,509 STATES. 963 00:36:46,509 --> 00:36:48,778 I PUT HERE IN THE LAST COUPLE 964 00:36:48,778 --> 00:36:49,813 LINES MAYBE WHAT'S MOST 965 00:36:49,813 --> 00:36:51,748 IMPORTANT FROM THIS THAT MAYBE 966 00:36:51,748 --> 00:36:53,717 THE RISK OF SEPSIS WAS NOT THAT 967 00:36:53,717 --> 00:36:55,285 DIFFERENT BASED ON RACE, MEANING 968 00:36:55,285 --> 00:36:57,020 GIVEN INFECTION WAS THE RISK OF 969 00:36:57,020 --> 00:36:59,122 SEPSIS, THIS IS THE OLDER 970 00:36:59,122 --> 00:37:01,524 DEFINITION OF SEPSIS MEANING 971 00:37:01,524 --> 00:37:03,059 PATIENTS WHO HAD CRITERIA AND 972 00:37:03,059 --> 00:37:04,961 MANIFESTATION THAT MIGHT HAVE 973 00:37:04,961 --> 00:37:06,429 RESULTED IN HOSPITALIZATION BUT 974 00:37:06,429 --> 00:37:09,165 GIVEN SEPSIS MEANING THAT 975 00:37:09,165 --> 00:37:11,167 INCIDENT INFECTION WITH 976 00:37:11,167 --> 00:37:11,901 INFLAMMATORY RESPONSE, ORGAN 977 00:37:11,901 --> 00:37:17,374 DYSFUNCTION WAS MORE FREQUENT IN 978 00:37:17,374 --> 00:37:17,974 BLACKS, SOMETHING WE'VE SEEN, 979 00:37:17,974 --> 00:37:20,443 KRISTINA RUDD TALKED ABOUT THAT. 980 00:37:20,443 --> 00:37:22,645 NOW WE'RE TALKING MORE ABOUT 981 00:37:22,645 --> 00:37:28,451 COMORBIDITIES AND LINK TO ACUTE 982 00:37:28,451 --> 00:37:29,419 ORGAN DYSFUNCTION. 983 00:37:29,419 --> 00:37:36,026 ONE WAY TO THINK ABOUT THIS IS 984 00:37:36,026 --> 00:37:37,327 RISK FACTORS FOR SEPSIS, GRAPH 985 00:37:37,327 --> 00:37:38,762 SHOWING LONGITUDINAL INCREASE IN 986 00:37:38,762 --> 00:37:49,272 RISK OF SEPSIS AT AGE BEYOND 50, 987 00:37:49,272 --> 00:37:52,108 INCREASES OVER TIME. 988 00:37:52,108 --> 00:37:53,843 USED DICHOTOMOUSLY, THE 989 00:37:53,843 --> 00:37:56,246 GOVERNMENT DEFINITION OF AGE OF 990 00:37:56,246 --> 00:37:59,649 65, YOU GET A RELATIVE RISK OF 991 00:37:59,649 --> 00:38:01,384 13 TIMES, PEOPLE OVER AGE 65, 13 992 00:38:01,384 --> 00:38:02,819 TIMES MORE LIKELY TO DEVELOP 993 00:38:02,819 --> 00:38:05,755 SEPSIS THAN PEOPLE WHO ARE 994 00:38:05,755 --> 00:38:06,089 YOUNGER. 995 00:38:06,089 --> 00:38:07,657 NEXT SLIDE. 996 00:38:07,657 --> 00:38:08,625 WHAT UNDERLIES THIS? 997 00:38:08,625 --> 00:38:10,894 THIS IS THE CONNECTION BACK TO 998 00:38:10,894 --> 00:38:12,962 HOW WE UNDERSTAND NOT JUST 999 00:38:12,962 --> 00:38:13,863 SOCIAL DETERMINANTS BUT 1000 00:38:13,863 --> 00:38:15,298 PARTICULARLY COMORBIDITIES, 1001 00:38:15,298 --> 00:38:15,632 SPECIFICALLY. 1002 00:38:15,632 --> 00:38:17,267 WE KNOW BLACKS, PEOPLE 1003 00:38:17,267 --> 00:38:19,102 IDENTIFIED AS BLACK, DO DEVELOP 1004 00:38:19,102 --> 00:38:21,971 SEPSIS AT THE YOUNGEST AGE ON 1005 00:38:21,971 --> 00:38:23,540 AVERAGE, SEPSIS OCCURS IN PEOPLE 1006 00:38:23,540 --> 00:38:25,442 BETWEEN 60 AND 65 YEARS OF AGE. 1007 00:38:25,442 --> 00:38:27,444 IN BLACK INDIVIDUALS, SEPSIS 1008 00:38:27,444 --> 00:38:28,578 OCCURS MUCH YOUNGER, USUALLY 1009 00:38:28,578 --> 00:38:30,280 BETWEEN 45 AND 50 YEARS OF AGE, 1010 00:38:30,280 --> 00:38:36,820 BUT WE ALSO KNOW FROM OTHER DATA 1011 00:38:36,820 --> 00:38:38,688 THAT BLACKS, ADULT BLACKS, USING 1012 00:38:38,688 --> 00:38:43,626 THE HER STUDY, DEVELOP 1013 00:38:43,626 --> 00:38:44,360 MULTI-MORBIDITY AT EARLIEST 1014 00:38:44,360 --> 00:38:46,029 STAGE, LOOKING AT OTHER 1015 00:38:46,029 --> 00:38:48,198 ETHNICITIES THEY DEVELOP CHRONIC 1016 00:38:48,198 --> 00:38:49,732 DISEASE AT FASTER RATE. 1017 00:38:49,732 --> 00:38:51,401 WE'RE TALKING ABOUT DIFFERENT 1018 00:38:51,401 --> 00:38:52,702 ELEMENTS, HOW THESE MIGHT PLAY 1019 00:38:52,702 --> 00:38:52,869 OUT. 1020 00:38:52,869 --> 00:38:58,508 WE KNOW FROM WHAT I SHOWED 1021 00:38:58,508 --> 00:39:00,477 EARLIER COMORBIDITIES CONTRIBUTE 1022 00:39:00,477 --> 00:39:03,513 TO RISK FOR SEPSIS, WE'VE SEEN 1023 00:39:03,513 --> 00:39:05,915 THAT, MAY WELL INTO THE RACE AND 1024 00:39:05,915 --> 00:39:08,118 GENDER DISPARITIES WE SEE BUT 1025 00:39:08,118 --> 00:39:09,352 NOW WE'RE SEEING INFLUENCE ON 1026 00:39:09,352 --> 00:39:11,754 AGE, HOW AGE IS A STRONG POTENT 1027 00:39:11,754 --> 00:39:15,258 RISK FACTOR FOR SEPSIS AS WELL. 1028 00:39:15,258 --> 00:39:17,460 NEXT SLIDE. 1029 00:39:17,460 --> 00:39:18,561 I'LL TALK ABOUT CANCER 1030 00:39:18,561 --> 00:39:20,730 SIMILARLY, IF YOU USE CANCER AS 1031 00:39:20,730 --> 00:39:22,265 A PROTOTYPE DISEASE, SO CANCER 1032 00:39:22,265 --> 00:39:23,566 PATIENTS ARE TEN TIMES MORE 1033 00:39:23,566 --> 00:39:24,467 LIKELY TO DEVELOP SEPSIS 1034 00:39:24,467 --> 00:39:26,102 COMPARED TO PATIENTS WHO DON'T 1035 00:39:26,102 --> 00:39:29,072 HAVE CANCER. 1036 00:39:29,072 --> 00:39:30,173 NEXT SLIDE. 1037 00:39:30,173 --> 00:39:34,210 AND IF YOU USE CANCER AS ONE 1038 00:39:34,210 --> 00:39:35,111 PHENOTYPE, IT'S ACTUALLY VERY 1039 00:39:35,111 --> 00:39:36,679 COMMON AND CANCER TURNS OUT TO 1040 00:39:36,679 --> 00:39:39,115 BE MAYBE THE MOST FREQUENT. 1041 00:39:39,115 --> 00:39:40,550 HIV INCREASED OVER TIME. 1042 00:39:40,550 --> 00:39:41,751 THESE ARE DATA FROM SEVERAL 1043 00:39:41,751 --> 00:39:42,652 YEARS AGO NOW. 1044 00:39:42,652 --> 00:39:44,954 IT LOOKS LIKE NOW IF YOU LOOK AT 1045 00:39:44,954 --> 00:39:47,257 THESE DATA MORE RECENTLY CANCER 1046 00:39:47,257 --> 00:39:49,459 AND HIV ARE PROBABLY SIMILAR IN 1047 00:39:49,459 --> 00:39:52,295 INCIDENCE RATES FOR SEPSIS BUT 1048 00:39:52,295 --> 00:39:53,263 AVERAGE RATE IS YELLOW LINE 1049 00:39:53,263 --> 00:39:55,665 ACROSS THE BOTTOM THAT YOU SEE, 1050 00:39:55,665 --> 00:39:59,936 300 CASES PER 100,000. 1051 00:39:59,936 --> 00:40:01,271 BUT CANCER, HIV, COPD AND EVEN 1052 00:40:01,271 --> 00:40:03,773 HEART DISEASE ARE RISK FACTORS 1053 00:40:03,773 --> 00:40:04,974 FOR DEVELOPING SEPSIS. 1054 00:40:04,974 --> 00:40:06,943 KRISTINA SHOWED YOU THAT NIGHT 1055 00:40:06,943 --> 00:40:10,013 FIGURE THAT DISPLAYED SOME OF 1056 00:40:10,013 --> 00:40:10,914 THOSE INCITING EVENTS, HOW THEY 1057 00:40:10,914 --> 00:40:13,316 PLAY OUT IN THE PLOT BUT WE KNOW 1058 00:40:13,316 --> 00:40:15,118 THESE ARE CONTRIBUTIONS NOT JUST 1059 00:40:15,118 --> 00:40:19,422 IN THE RISK FOR INFECTION BUT IN 1060 00:40:19,422 --> 00:40:26,763 RISK OF ORGAN DYSFUNCTION AS 1061 00:40:26,763 --> 00:40:27,397 WELL. 1062 00:40:27,397 --> 00:40:27,964 NEXT SLIDE. 1063 00:40:27,964 --> 00:40:30,033 WE'VE STUDIED THIS IN OUR OWN 1064 00:40:30,033 --> 00:40:33,102 HOSPITAL SYSTEM, A COUPLE TIMES 1065 00:40:33,102 --> 00:40:33,336 NOW. 1066 00:40:33,336 --> 00:40:39,008 ONE OF THE THINGS APPARENT, IF 1067 00:40:39,008 --> 00:40:40,543 YOU'RE TRYING TO UNDERSTAND 1068 00:40:40,543 --> 00:40:42,612 WHETHER IT CONTRIBUTES TO ORGAN 1069 00:40:42,612 --> 00:40:45,815 DYSFUNCTION IT'S LESS CLEAR. 1070 00:40:45,815 --> 00:40:48,218 WE SEE THAT SIGNALS SUCH AS 1071 00:40:48,218 --> 00:40:58,695 ORGAN DYSFUNCTION ARE STRONG 1072 00:41:03,933 --> 00:41:04,834 PREDICTORS. 1073 00:41:04,834 --> 00:41:07,036 WE FOUND THEY WERE HOSPITALIZED 1074 00:41:07,036 --> 00:41:11,441 WITH LOW CD4 COUNT, NOT ON 1075 00:41:11,441 --> 00:41:14,944 ANTIRETROVIRAL THERAPY, STRONG 1076 00:41:14,944 --> 00:41:16,112 RISK FACTORS FOR INFECTION, 1077 00:41:16,112 --> 00:41:19,315 STRONG RISK FACTOR FOR MORTALITY 1078 00:41:19,315 --> 00:41:19,549 AS WELL. 1079 00:41:19,549 --> 00:41:20,416 NEXT SLIDE. 1080 00:41:20,416 --> 00:41:22,151 IF YOU USE ADJUSTED ANALYSIS, 1081 00:41:22,151 --> 00:41:23,419 LOOK AT OTHER VARIABLES THAT 1082 00:41:23,419 --> 00:41:26,222 MIGHT PREDICT THIS WHAT YOU SEE 1083 00:41:26,222 --> 00:41:31,561 IS HIV HAS AN ODDS RATIO OF 2 1084 00:41:31,561 --> 00:41:36,599 FOR MORTALITY, INCLUDING 1085 00:41:36,599 --> 00:41:37,900 SEVERITY OF ILLNESS, THIS IS 1086 00:41:37,900 --> 00:41:39,669 TRACKS WITH INCREASED RISK OF 1087 00:41:39,669 --> 00:41:41,738 INFECTION, TRACKS TO INCREASED 1088 00:41:41,738 --> 00:41:43,273 RISK OF HOSPITAL MORTALITY, 1089 00:41:43,273 --> 00:41:44,941 WHAT'S LESS CLEAR IS OBVIOUSLY 1090 00:41:44,941 --> 00:41:46,442 THE SOCIAL DETERMINANTS THAT GO 1091 00:41:46,442 --> 00:41:48,411 ALONG WITH HIV WHICH WE DO 1092 00:41:48,411 --> 00:41:50,480 UNDERSTAND BUT WHETHER IT 1093 00:41:50,480 --> 00:41:51,114 CONTRIBUTES TO ORGAN 1094 00:41:51,114 --> 00:41:53,883 DYSFUNCTION, WE'VE SEEN IN OTHER 1095 00:41:53,883 --> 00:41:54,984 PHENOTYPES FOR INSTANCE CANCER, 1096 00:41:54,984 --> 00:41:58,254 WHERE RISK OF INFECTION IS TIED 1097 00:41:58,254 --> 00:42:00,123 TO SOURCE OF CANCER, RESPIRATORY 1098 00:42:00,123 --> 00:42:02,625 INFECTION AND CANCERS TEND TO GO 1099 00:42:02,625 --> 00:42:06,896 TOGETHER BUT ORGAN DYSFUNCTION 1100 00:42:06,896 --> 00:42:08,331 AS WELL. 1101 00:42:08,331 --> 00:42:09,866 THE QUESTION REMAINS, IT'S 1102 00:42:09,866 --> 00:42:12,969 REALLY BEEN POSED IMPORTANTLY 1103 00:42:12,969 --> 00:42:13,903 HERE TODAY, IS MULTI-MORBIDITY 1104 00:42:13,903 --> 00:42:16,205 IS A MAJOR COMPONENT OF SEPSIS 1105 00:42:16,205 --> 00:42:19,609 AND WHY SEPSIS OCCURS AT ALL, SO 1106 00:42:19,609 --> 00:42:21,144 THIS IS A CASE PROPORTION 1107 00:42:21,144 --> 00:42:22,545 REPRESENTING COMORBIDITIES THAT 1108 00:42:22,545 --> 00:42:24,480 WE SEE AMONG SEPSIS PATIENTS, 1109 00:42:24,480 --> 00:42:26,916 AND CLEARLY SOME OF THESE ARE 1110 00:42:26,916 --> 00:42:28,885 THINGS RISK FACTORS FOR 1111 00:42:28,885 --> 00:42:31,954 INFECTION, THINGS LIKE CANCER, 1112 00:42:31,954 --> 00:42:32,922 COPD, CHRONIC KIDNEY DISEASE, 1113 00:42:32,922 --> 00:42:35,558 BUT SOME LESS SO. 1114 00:42:35,558 --> 00:42:37,760 YOU SEE HIV IS LOWER PROPORTION 1115 00:42:37,760 --> 00:42:40,930 BUT THE REASON I SHOWED HIV AS A 1116 00:42:40,930 --> 00:42:42,031 SPECIFIC COMORBIDITY IS IN 1117 00:42:42,031 --> 00:42:44,634 CERTAIN SUBSETS OF PATIENTS WITH 1118 00:42:44,634 --> 00:42:46,703 HIV THE RISK IS MUCH HIGHER, WE 1119 00:42:46,703 --> 00:42:48,905 DO KNOW THERE'S A STRONG 1120 00:42:48,905 --> 00:42:50,139 COMPONENT OF SOCIAL DETERMINANTS 1121 00:42:50,139 --> 00:42:54,010 AND HEALTH EQUITY THAT PLAYS OUT 1122 00:42:54,010 --> 00:42:56,746 IN HIV AS WELL. 1123 00:42:56,746 --> 00:43:00,950 I WANT TO SUMMARIZE TALKING 1124 00:43:00,950 --> 00:43:01,784 ABOUT CHRONIC CO-MORBIDITIES, 1125 00:43:01,784 --> 00:43:02,852 CLEARLY THE PRESENCE OF 1126 00:43:02,852 --> 00:43:04,187 COMORBIDITIES MAY BE SIMILAR 1127 00:43:04,187 --> 00:43:05,822 BETWEEN RACES BUT OCCURS WITH 1128 00:43:05,822 --> 00:43:07,557 GREATER SEVERITY IN BLACKS AND 1129 00:43:07,557 --> 00:43:09,659 MALES, THAT PLAYS A ROLE IN SOME 1130 00:43:09,659 --> 00:43:11,194 DISPARITIES THAT WE SEE IN 1131 00:43:11,194 --> 00:43:12,729 INCIDENCE OF SEPSIS. 1132 00:43:12,729 --> 00:43:14,697 THE RISK OF ORGAN DYSFUNCTION 1133 00:43:14,697 --> 00:43:16,232 INCREASES WITH NUMBER AND 1134 00:43:16,232 --> 00:43:18,501 SEVERITY OF CHRONIC CONDITIONS, 1135 00:43:18,501 --> 00:43:19,836 WHEN WE'RE TALKING ABOUT 1136 00:43:19,836 --> 00:43:21,904 INDIVIDUAL CONDITIONS SOME ARE 1137 00:43:21,904 --> 00:43:24,006 MORE SEVERE, SOME REPRESENT -- 1138 00:43:24,006 --> 00:43:27,510 HIV FOR INSTANCE LOW CD4 COUNT, 1139 00:43:27,510 --> 00:43:28,911 NOT ON ANTIRETROVIRAL, HAS 1140 00:43:28,911 --> 00:43:31,447 HIGHER RISK OF DEVELOPING SEPSIS 1141 00:43:31,447 --> 00:43:32,849 AND SEPSIS-RELATED MORTALITY BUT 1142 00:43:32,849 --> 00:43:35,051 ALSO THE NUMBER OF COMORBIDITIES 1143 00:43:35,051 --> 00:43:37,453 AS WELL WHICH KRISTINA SHOWED, 1144 00:43:37,453 --> 00:43:40,256 THE CUMULATIVE EFFECT RESULTS OR 1145 00:43:40,256 --> 00:43:43,259 REPRESENTING MULTI-MORBIDITY, 1146 00:43:43,259 --> 00:43:45,661 WHAT I SHOWED IS THAT A LOT OF 1147 00:43:45,661 --> 00:43:47,730 COMORBIDITIES ARE MORE RAPIDLY 1148 00:43:47,730 --> 00:43:50,266 DEVELOPED, CUMULATIVELY AND OVER 1149 00:43:50,266 --> 00:44:00,710 TIME, IN NON-CAUCASIAN OR 1150 00:44:07,817 --> 00:44:08,518 NON-WHITE RACES. 1151 00:44:08,518 --> 00:44:10,486 HOW WE UNDERSTAND SOCIAL 1152 00:44:10,486 --> 00:44:11,587 DISPARITIES, DISPARITIES THAT 1153 00:44:11,587 --> 00:44:13,890 RESULTS, HOW WE MIGHT APPLY IN 1154 00:44:13,890 --> 00:44:14,323 SEPSIS. 1155 00:44:14,323 --> 00:44:17,927 IF WE UNDERSTAND WHAT LOOKS LIKE 1156 00:44:17,927 --> 00:44:19,796 SEPSIS MORTALITY, SO ONE WAY TO 1157 00:44:19,796 --> 00:44:22,432 THINK ABOUT IT, DARKER STATES OR 1158 00:44:22,432 --> 00:44:32,942 PLACES WITH HIGHER NUMBERS OF 1159 00:44:34,343 --> 00:44:37,046 DEATHS, YOU WITH BREAK THIS IN 1160 00:44:37,046 --> 00:44:37,313 CLUSTERS. 1161 00:44:37,313 --> 00:44:38,648 ACROSS THE UNITED STATES THERE'S 1162 00:44:38,648 --> 00:44:48,958 HOT SPOTS OF WHAT I CALL HOT 1163 00:44:48,958 --> 00:44:59,435 SPOTS FOR SEPSIS MORTALITY. 1164 00:45:04,006 --> 00:45:05,675 YOU'RE SEEK THE STROKE BELT AND 1165 00:45:05,675 --> 00:45:08,077 CARDIOVASCULAR DISEASE BELT. 1166 00:45:08,077 --> 00:45:08,845 IN THESE AREAS ACROSS THE 1167 00:45:08,845 --> 00:45:09,846 SOUTHEAST UNITED STATES AND 1168 00:45:09,846 --> 00:45:12,014 PARTICULARLY FOR US IN GEORGIA 1169 00:45:12,014 --> 00:45:13,683 THAT AREA ACROSS MIDDLE GEORGIA 1170 00:45:13,683 --> 00:45:15,985 IN THE MIDDLE THAT REPRESENTS 1171 00:45:15,985 --> 00:45:18,588 SOUTH OF ATLANTA IS AN AREA WITH 1172 00:45:18,588 --> 00:45:29,098 RELATIVE HEALTH CARE DESERTS, 1173 00:45:32,768 --> 00:45:34,470 HIGH RATE OF MOMENTS, THEY ARE 1174 00:45:34,470 --> 00:45:35,905 TIGHTLY TIED TO COMORBIDITIES IN 1175 00:45:35,905 --> 00:45:40,510 THOSE AREAS AS WELL. 1176 00:45:40,510 --> 00:45:41,511 NEXT SLIDE. 1177 00:45:41,511 --> 00:45:43,012 IN CONCLUSION I KNOW YOU REALIZE 1178 00:45:43,012 --> 00:45:43,880 HOW IMPORTANT SEPSIS IS. 1179 00:45:43,880 --> 00:45:46,749 IT IS ONE OF THE MOST COMMON AND 1180 00:45:46,749 --> 00:45:48,618 LETHAL DISEASES WE DEAL WITH. 1181 00:45:48,618 --> 00:45:51,988 WE CLEARLY SEE IT ALL OVER THE 1182 00:45:51,988 --> 00:45:55,157 WORLD, THE MORTALITY IS TIED TO 1183 00:45:55,157 --> 00:45:56,592 ATTENTIVENESS AND EFFORTS TO 1184 00:45:56,592 --> 00:45:58,094 IDENTIFYING SEPSIS PARTICULARLY 1185 00:45:58,094 --> 00:45:59,328 IN A TIMELY MANNER, HAVING 1186 00:45:59,328 --> 00:46:01,831 THINGS IN PLACE TO PREVENT AND 1187 00:46:01,831 --> 00:46:03,065 TREAT THE DISEASE. 1188 00:46:03,065 --> 00:46:04,367 COMORBIDITIES AS I'VE SHOWN ARE 1189 00:46:04,367 --> 00:46:05,801 NOT JUST COMMON IN SEPSIS, THEY 1190 00:46:05,801 --> 00:46:06,669 ARE THE RULE. 1191 00:46:06,669 --> 00:46:09,305 THEY ARE THE THING WE SEE VERY 1192 00:46:09,305 --> 00:46:11,474 COMMONLY AND BOTH -- THEY ATTACH 1193 00:46:11,474 --> 00:46:13,576 OR ASSOCIATE TO THE RISK OF 1194 00:46:13,576 --> 00:46:15,077 SEPSIS, RISK OF ORGAN 1195 00:46:15,077 --> 00:46:15,745 DYSFUNCTION AND MORTALITY THAT 1196 00:46:15,745 --> 00:46:17,280 GOES WITH IT. 1197 00:46:17,280 --> 00:46:19,448 AND THE RACIAL AND GENDER 1198 00:46:19,448 --> 00:46:20,550 DISPARITIES, EVEN OTHER THINGS 1199 00:46:20,550 --> 00:46:25,054 WE SEE IN DISPARITIES IN UP 1200 00:46:25,054 --> 00:46:27,557 SEPSIS ARE TIED TO PRESENCE OF 1201 00:46:27,557 --> 00:46:29,659 COMORBIDITIES, NUMBER OF 1202 00:46:29,659 --> 00:46:30,960 COMORBIDITIES, SPECIFIC TYPE OF 1203 00:46:30,960 --> 00:46:32,161 COMORBIDITY AND SEVERITY AS 1204 00:46:32,161 --> 00:46:32,595 WELL. 1205 00:46:32,595 --> 00:46:33,462 THANK YOU VERY MUCH. 1206 00:46:33,462 --> 00:46:43,973 YOU CAN GO TO THE NEXT SLIDE. 1207 00:46:46,409 --> 00:46:47,510 >> WE HAVE TIME FOR ONE 1208 00:46:47,510 --> 00:46:47,944 QUESTION. 1209 00:46:47,944 --> 00:46:49,445 STATE YOUR NAME AND INSTITUTION. 1210 00:46:49,445 --> 00:46:51,781 A QUESTION IN THE CHAT, GREG, 1211 00:46:51,781 --> 00:46:53,282 THE PRESENTATION SUGGESTS 1212 00:46:53,282 --> 00:46:55,151 INCREASED RISK OF DEVELOPING 1213 00:46:55,151 --> 00:46:57,987 SEPSIS BASED ON RACE OR 1214 00:46:57,987 --> 00:46:59,322 ETHNICITY. 1215 00:46:59,322 --> 00:47:02,391 IN U.S. THESE GROUPS TEND TO BE 1216 00:47:02,391 --> 00:47:04,594 SOCIOECONOMIC GROUPS THAT 1217 00:47:04,594 --> 00:47:04,860 STRUGGLE. 1218 00:47:04,860 --> 00:47:05,895 IS THERE STRATIFICATION, DOES 1219 00:47:05,895 --> 00:47:08,531 THE RATE OF SEPSIS AND MORBIDITY 1220 00:47:08,531 --> 00:47:09,532 REMAIN THE SAME RACIALLY? 1221 00:47:09,532 --> 00:47:12,902 >> YEAH, IT'S A REALLY GOOD 1222 00:47:12,902 --> 00:47:13,669 QUESTION. 1223 00:47:13,669 --> 00:47:20,943 HOW MUCH MUCH DISPARITIES IN 1224 00:47:20,943 --> 00:47:22,778 SEPSIS INCIDENCE, PARTICULARLY 1225 00:47:22,778 --> 00:47:23,446 WHEN YOU ADJUST FOR 1226 00:47:23,446 --> 00:47:25,114 SOCIOECONOMICS, NOT DONE AS 1227 00:47:25,114 --> 00:47:27,817 OFTEN, MORE DIFFICULT TO DO, IT 1228 00:47:27,817 --> 00:47:29,785 MITIGATES EFFECT BUT DOESN'T GO 1229 00:47:29,785 --> 00:47:30,186 AWAY. 1230 00:47:30,186 --> 00:47:31,854 SO WHEN I THINK ABOUT IT, IT'S 1231 00:47:31,854 --> 00:47:33,923 ONE OF THE COMPONENTS, AND I 1232 00:47:33,923 --> 00:47:35,591 THINK IT'S STILL DIFFICULT TO 1233 00:47:35,591 --> 00:47:36,959 ADJUST FOR THAT COMPLETELY, 1234 00:47:36,959 --> 00:47:37,159 RIGHT? 1235 00:47:37,159 --> 00:47:39,528 BUT AT THE SAME TIME IT DOESN'T 1236 00:47:39,528 --> 00:47:45,868 SEEM LIKE IT MAKES THE ENTIRE 1237 00:47:45,868 --> 00:47:47,737 DISPARITY GO AWAY OR BECOME 1238 00:47:47,737 --> 00:47:56,445 DIFFERENT, BECOME THE SAME FOR 1239 00:47:56,445 --> 00:47:58,147 ALL THE STRATA, FOR INSTANCE. 1240 00:47:58,147 --> 00:47:59,982 >> I HAVE A QUESTION. 1241 00:47:59,982 --> 00:48:02,618 >> GO AHEAD. 1242 00:48:02,618 --> 00:48:05,788 >> I SAW YOUR MAP, THE BELT YOU 1243 00:48:05,788 --> 00:48:08,958 SHOWED US ALSO HOT AND HUMID 1244 00:48:08,958 --> 00:48:12,461 REGIONS OF THE -- ESPECIALLY IN 1245 00:48:12,461 --> 00:48:12,795 THE U.S. 1246 00:48:12,795 --> 00:48:15,831 DO YOU THINK THAT PLAYS? 1247 00:48:15,831 --> 00:48:16,999 >> SORRY, THE REGIONS -- 1248 00:48:16,999 --> 00:48:18,267 >> THE REGIONS, ATLANTA AND 1249 00:48:18,267 --> 00:48:19,902 THOSE AREAS, SOUTHERN AREAS, 1250 00:48:19,902 --> 00:48:23,606 ALSO THE AREAS MORE HUMID AND 1251 00:48:23,606 --> 00:48:24,373 HOT. 1252 00:48:24,373 --> 00:48:25,374 >> OH, I SEE. 1253 00:48:25,374 --> 00:48:26,842 >> DOES THAT PLAY OR DO YOU SEE 1254 00:48:26,842 --> 00:48:28,944 ALL THE OVER THE GLOBE THE BELT 1255 00:48:28,944 --> 00:48:30,179 PLAYS A ROLE? 1256 00:48:30,179 --> 00:48:32,014 >> IT'S A GOOD QUESTION, IT MAY 1257 00:48:32,014 --> 00:48:35,017 BE ONE KRISTINA WANTS TO THINK 1258 00:48:35,017 --> 00:48:35,618 ABOUT FROM GLOBAL PERSPECTIVE 1259 00:48:35,618 --> 00:48:37,620 BUT I DON'T THINK THAT IS THE 1260 00:48:37,620 --> 00:48:38,921 ANSWER COMPLETELY LARGELY 1261 00:48:38,921 --> 00:48:40,356 BECAUSE WE'VE SEEN SIMILAR DATA 1262 00:48:40,356 --> 00:48:42,658 OVER MANY YEARS, I WOULD NOT AT 1263 00:48:42,658 --> 00:48:44,093 ALL DISPUTE CLIMATE CHANGE 1264 00:48:44,093 --> 00:48:49,231 CERTAINLY IS CHANGING BOTH THE 1265 00:48:49,231 --> 00:48:49,832 ORGANISMS AND SUSCEPTIBILITY, 1266 00:48:49,832 --> 00:48:51,434 BUT I DON'T THINK IT EXPLAINS 1267 00:48:51,434 --> 00:48:57,640 WHAT WE'RE SEEING ON THAT 1268 00:48:57,640 --> 00:48:58,374 GEOGRAPHIC COUNTY-BY-COUNTY 1269 00:48:58,374 --> 00:48:59,575 LEVELS, IT'S MORE RELATED TO 1270 00:48:59,575 --> 00:49:01,911 COMORBIDITIES, ACCESS TO HEALTH 1271 00:49:01,911 --> 00:49:02,712 CARE, EDUCATION, SOCIAL 1272 00:49:02,712 --> 00:49:06,348 DETERMINANTS THAT WE THINK OF AS 1273 00:49:06,348 --> 00:49:12,154 INVARIABLY IN PLACE AND 1274 00:49:12,154 --> 00:49:15,558 CONTRIBUTING MORE STRONGLY. 1275 00:49:15,558 --> 00:49:16,325 >> ONE MORE QUESTION, ADAM 1276 00:49:16,325 --> 00:49:19,395 LEVINE AT BROWN. 1277 00:49:19,395 --> 00:49:20,963 SO, FROM KRISTINA, SORRY, 1278 00:49:20,963 --> 00:49:22,331 INTERESTING WORK ON RELATIONSHIP 1279 00:49:22,331 --> 00:49:24,533 BETWEEN ENVIRONMENT AND SEPSIS. 1280 00:49:24,533 --> 00:49:25,835 THANK YOU. 1281 00:49:25,835 --> 00:49:26,502 >> WHICH DEFINITELY EXISTS BUT I 1282 00:49:26,502 --> 00:49:29,338 DON'T THINK AT LEAST THE HEAT 1283 00:49:29,338 --> 00:49:30,206 MAPS, WHAT I'M THINKING OF HOT 1284 00:49:30,206 --> 00:49:31,640 SPOT MAPS, I DON'T THINK IT 1285 00:49:31,640 --> 00:49:34,944 EXPLAINS ALL OF THAT. 1286 00:49:34,944 --> 00:49:35,578 >> THANK YOU. 1287 00:49:35,578 --> 00:49:39,348 WE'LL MOVE TO THE NEXT SPEAKER, 1288 00:49:39,348 --> 00:49:41,584 DR. CHRISTOPHER CHESLEY, 1289 00:49:41,584 --> 00:49:42,718 UNIVERSITY OF PENNSYLVANIA, 1290 00:49:42,718 --> 00:49:47,389 DISCUSSING MECHANISMS OF RACIAL 1291 00:49:47,389 --> 00:49:51,227 DISPARITIES IN SEPSIS. 1292 00:49:51,227 --> 00:49:52,862 >> CAN EVERYONE HEAR ME? 1293 00:49:52,862 --> 00:49:53,329 >> YES. 1294 00:49:53,329 --> 00:49:57,700 >> THANKS FOR THE INTRODUCTION. 1295 00:49:57,700 --> 00:49:59,368 THANKS FOR EXTENDING THE 1296 00:49:59,368 --> 00:50:00,669 OPPORTUNITY TO GIVE THIS 1297 00:50:00,669 --> 00:50:03,072 PRESENTATION, TO BE PART OF 1298 00:50:03,072 --> 00:50:04,073 DIALOGUE WITH PROMINENT 1299 00:50:04,073 --> 00:50:06,242 RESEARCHERS IN THE FIELD. 1300 00:50:06,242 --> 00:50:08,210 I'M CHRISTOPHER CHESLEY, 1301 00:50:08,210 --> 00:50:10,846 ASSISTANT PROFESSOR OF MEDICINE, 1302 00:50:10,846 --> 00:50:11,514 ADULT PULMONARY CARE MEDICINE, 1303 00:50:11,514 --> 00:50:13,048 UNIVERSITY OF PENNSYLVANIA. 1304 00:50:13,048 --> 00:50:15,918 I'VE BEEN TASKED TO TALK ABOUT 1305 00:50:15,918 --> 00:50:17,119 MECHANISMS OF RACIAL 1306 00:50:17,119 --> 00:50:18,954 DISPARITIES, A TALK THAT'S GOING 1307 00:50:18,954 --> 00:50:20,556 TO DOVETAIL WITH THE TWO 1308 00:50:20,556 --> 00:50:24,226 PREVIOUS AND ADD TO THE 1309 00:50:24,226 --> 00:50:25,194 CONVERSATION DIFFERENT THAN WHAT 1310 00:50:25,194 --> 00:50:28,030 WE'VE BEEN DISCUSSING SO FAR. 1311 00:50:28,030 --> 00:50:31,000 NEXT SLIDE. 1312 00:50:31,000 --> 00:50:33,536 I'M FUNDED BY A DEVELOPMENT 1313 00:50:33,536 --> 00:50:36,705 AWARD FROM NHLBI. 1314 00:50:36,705 --> 00:50:37,673 NEXT SLIDE. 1315 00:50:37,673 --> 00:50:39,742 OBJECTIVE OF THE TALK, DISCUSS 1316 00:50:39,742 --> 00:50:42,178 SEPSIS RELEVANT DEFINITION OF 1317 00:50:42,178 --> 00:50:43,913 RACISM, IDENTIFY KNOWN 1318 00:50:43,913 --> 00:50:46,315 DISPARITIES RELATED TO SEPSIS, 1319 00:50:46,315 --> 00:50:48,751 DISCUSS SOME MOST RESEARCH 1320 00:50:48,751 --> 00:50:50,386 THEORIES FOR MECHANISMS, 1321 00:50:50,386 --> 00:50:51,921 EVALUATE STRENGTH OF THEORIES 1322 00:50:51,921 --> 00:50:54,890 THAT KIND OF ENCOMPASS 1323 00:50:54,890 --> 00:50:56,425 MECHANISMS AND DESCRIBE FUTURE 1324 00:50:56,425 --> 00:50:56,759 DIRECTIONS. 1325 00:50:56,759 --> 00:50:57,493 NEXT SLIDE. 1326 00:50:57,493 --> 00:51:00,229 WHY IS IT IMPORTANT TO BEGIN THE 1327 00:51:00,229 --> 00:51:02,565 CONVERSATION WITH DEFINITION OF 1328 00:51:02,565 --> 00:51:02,798 RACISM? 1329 00:51:02,798 --> 00:51:04,633 HOW IT'S RELEVANT TO THE DISEASE 1330 00:51:04,633 --> 00:51:07,803 OF SEPSIS IN PARTICULAR. 1331 00:51:07,803 --> 00:51:09,438 IT'S IMPORTANT TO ACKNOWLEDGE 1332 00:51:09,438 --> 00:51:10,940 ADVERSE OUTCOMES WHICH WE 1333 00:51:10,940 --> 00:51:12,608 DISCUSS IN CONTEXT OF RACIAL 1334 00:51:12,608 --> 00:51:16,412 DISPARITIES ARE ALSO -- CAN BE 1335 00:51:16,412 --> 00:51:18,747 THOUGHT OF MANIFESTATIONS EVER 1336 00:51:18,747 --> 00:51:20,683 STRUCTURAL RACISM. 1337 00:51:20,683 --> 00:51:21,617 WE ARE FAMILIAR WITH OUTCOMES, 1338 00:51:21,617 --> 00:51:23,652 DIFFERENT OUTCOMES BY NATURE OF 1339 00:51:23,652 --> 00:51:24,653 OUR PROFESSIONALS ROLES. 1340 00:51:24,653 --> 00:51:26,088 IT'S MORE THAN TO FRAME THIS 1341 00:51:26,088 --> 00:51:29,692 DISCUSSION NOT JUST ABOUT RACIAL 1342 00:51:29,692 --> 00:51:32,962 DISPARITIES BUT ALSO HOW 1343 00:51:32,962 --> 00:51:37,800 MULTIPLE FORCES THAT DECLINES 1344 00:51:37,800 --> 00:51:38,801 STRUCTURAL DISADVANTAGE 1345 00:51:38,801 --> 00:51:42,171 CULMINATE IN MEDICAL RACISM. 1346 00:51:42,171 --> 00:51:43,606 DEFINING TERMS FIRST, DEFINITION 1347 00:51:43,606 --> 00:51:47,643 OF -- CONCEPT OF RACE, A SOCIAL 1348 00:51:47,643 --> 00:51:48,744 CLASSIFICATION OF PEOPLE BASED 1349 00:51:48,744 --> 00:51:52,147 ON PHYSICAL OR OBSERVED 1350 00:51:52,147 --> 00:51:52,982 CHARACTERISTICS. 1351 00:51:52,982 --> 00:51:54,884 RACISM BECOMES THE STRUCTURING 1352 00:51:54,884 --> 00:51:56,652 OF OPPORTUNITY FROM SYSTEMIC 1353 00:51:56,652 --> 00:51:57,720 PERSPECTIVE THAT RELIES ON 1354 00:51:57,720 --> 00:52:00,589 ASSIGNING VALUE BASED ON SOCIAL 1355 00:52:00,589 --> 00:52:05,494 DEFINABLE PHENOTYPES. 1356 00:52:05,494 --> 00:52:07,363 THREE THINGS IT DOES, 1357 00:52:07,363 --> 00:52:09,331 DISADVANTAGES SOME INDIVIDUALS 1358 00:52:09,331 --> 00:52:10,766 AND COMMUNITIES, UNFAIRLY 1359 00:52:10,766 --> 00:52:13,269 ADVANTAGES OTHER INDIVIDUALS AND 1360 00:52:13,269 --> 00:52:15,704 OTHER COMMUNITIES, AND THROUGH 1361 00:52:15,704 --> 00:52:18,207 THAT KINDS OF SYNERGISTIC 1362 00:52:18,207 --> 00:52:18,774 RELATIONSHIP UNDERMINES 1363 00:52:18,774 --> 00:52:20,943 REALIZATION OF FULL POTENTIAL OF 1364 00:52:20,943 --> 00:52:23,579 AN ENTIRE SOCIETY THROUGH WASTED 1365 00:52:23,579 --> 00:52:25,080 HUMAN RESOURCES. 1366 00:52:25,080 --> 00:52:26,782 NEXT SLIDE. 1367 00:52:26,782 --> 00:52:30,853 SO RACISM CAN BE MEDIATED IN AT 1368 00:52:30,853 --> 00:52:32,988 LEAST TWO WAYS, I THINK TWO 1369 00:52:32,988 --> 00:52:36,859 PARTICULARLY USEFUL FOR 1370 00:52:36,859 --> 00:52:45,734 DISCUSSION TODAY, PERSONALLY 1371 00:52:45,734 --> 00:52:47,403 MEDIATED AND INSTITUTIONAL. 1372 00:52:47,403 --> 00:52:48,704 DISCRIMINATION REFERS TO 1373 00:52:48,704 --> 00:52:50,239 DIFFERENTIAL ACTION TOWARD 1374 00:52:50,239 --> 00:52:53,409 OTHERS BY RACE, CULMINATES INTO 1375 00:52:53,409 --> 00:52:54,009 DIFFERENT OUTCOMES AND ACCESS 1376 00:52:54,009 --> 00:52:55,044 AND POTENTIAL. 1377 00:52:55,044 --> 00:53:01,717 IT'S IMPORTANT TO ACKNOWLEDGE 1378 00:53:01,717 --> 00:53:03,052 THAT PERSONALLY MEDIATED CAN BE 1379 00:53:03,052 --> 00:53:06,855 INTENTIONAL OR NOT INTENTIONAL. 1380 00:53:06,855 --> 00:53:08,290 IN ADDITION, THIS CONCEPT OF 1381 00:53:08,290 --> 00:53:09,825 INSTITUTIONALIZED RACISM WHICH 1382 00:53:09,825 --> 00:53:11,260 REFERS TO STRUCTURES, POLICIES, 1383 00:53:11,260 --> 00:53:13,462 PRACTICES AND NORMS THAT RESULT 1384 00:53:13,462 --> 00:53:16,231 AND DIFFERENTIAL ACCESS TO 1385 00:53:16,231 --> 00:53:18,367 GOODS, SERVICES, OPPORTUNITIES, 1386 00:53:18,367 --> 00:53:19,902 WITHIN SOCIETIES BASED ON RACE, 1387 00:53:19,902 --> 00:53:21,203 MANIFESTED AS DIFFERENTIAL 1388 00:53:21,203 --> 00:53:22,972 ACCESS TO MATERIAL CONDITIONS, 1389 00:53:22,972 --> 00:53:24,840 THINGS LIKE QUALITY EDUCATION, 1390 00:53:24,840 --> 00:53:27,443 HOUSING, EVEN ACCESS TO 1391 00:53:27,443 --> 00:53:28,978 APPROPRIATE MEDICAL FACILITIES, 1392 00:53:28,978 --> 00:53:32,047 POWER WHICH CAN REFER TO THE 1393 00:53:32,047 --> 00:53:34,249 ABILITY TO INTAKE AND TO 1394 00:53:34,249 --> 00:53:36,218 LEVERAGE AND BE PART OF 1395 00:53:36,218 --> 00:53:38,687 INFORMATION GATHERING AND 1396 00:53:38,687 --> 00:53:39,488 FINANCIAL RESOURCES, AND EVEN 1397 00:53:39,488 --> 00:53:41,256 VOICE, ABILITY TO TELL ONE'S OWN 1398 00:53:41,256 --> 00:53:43,659 HISTORY AND TO BE REPRESENTED IN 1399 00:53:43,659 --> 00:53:54,169 THINGS SUCH AS MEDIA, EVEN IN 1400 00:53:56,238 --> 00:53:57,439 WORKING GROUPS. 1401 00:53:57,439 --> 00:54:02,344 IN TERMS OF TOUCHSTONES TO MOVE 1402 00:54:02,344 --> 00:54:03,679 TOWARDS DEFINITIONS OF RACISM 1403 00:54:03,679 --> 00:54:04,880 PROXIMAL TO OUR DISCUSSION 1404 00:54:04,880 --> 00:54:07,383 TODAY, MEDICAL RACISM IS 1405 00:54:07,383 --> 00:54:08,250 STRUCTURES, POLICIES, PRACTICES, 1406 00:54:08,250 --> 00:54:10,452 NORMS THAT CULMINATE IN 1407 00:54:10,452 --> 00:54:11,553 DIFFERENTIAL ACCESS IN DELIVERY, 1408 00:54:11,553 --> 00:54:12,654 EXPERIENCE OF HIGH QUALITY 1409 00:54:12,654 --> 00:54:15,024 MEDICAL CARE, THAT RESULT IN 1410 00:54:15,024 --> 00:54:16,625 INEQUITABLE CLINICAL PROCESSES 1411 00:54:16,625 --> 00:54:17,760 AND OUTCOMES. 1412 00:54:17,760 --> 00:54:19,428 FROM THAT DEFINITION OF MEDICAL 1413 00:54:19,428 --> 00:54:29,805 RACISM WE CAN THINK ABOUT 1414 00:54:29,805 --> 00:54:33,842 SEPSIS-RELEVANT RACISM RESULTS 1415 00:54:33,842 --> 00:54:35,077 IN DISPROPORTIONATELY RISK OF 1416 00:54:35,077 --> 00:54:39,982 MORBIDITY AND MORTALITY. 1417 00:54:39,982 --> 00:54:41,483 CONCEIVES OF SEPSIS RELEVANT, 1418 00:54:41,483 --> 00:54:43,385 TWO LOCATIONS, FIRST IN HEALTH 1419 00:54:43,385 --> 00:54:46,655 SYSTEMS, SECOND OUTSIDE OF THEM. 1420 00:54:46,655 --> 00:54:48,857 NEXT SLIDE. WHAT IS THE 1421 00:54:48,857 --> 00:54:51,794 EVIDENCE FOR DISPARITIES IN 1422 00:54:51,794 --> 00:54:52,027 SEPSIS? 1423 00:54:52,027 --> 00:54:52,795 NEXT SLIDE. 1424 00:54:52,795 --> 00:54:56,298 SOME OF THESE DATA WILL BE AN 1425 00:54:56,298 --> 00:55:00,335 ECHO OF PREVIOUS SPEAKER, BUT AS 1426 00:55:00,335 --> 00:55:02,404 WAS MENTIONED CERTAIN 1427 00:55:02,404 --> 00:55:03,505 MINORITIZED RACES HAVE INCREASED 1428 00:55:03,505 --> 00:55:05,040 INCIDENCE OF SEPSIS COMPARED TO 1429 00:55:05,040 --> 00:55:05,441 OTHERS. 1430 00:55:05,441 --> 00:55:10,279 SO IN THE SPECIFIC CASE OF 1431 00:55:10,279 --> 00:55:12,281 BLACK, IDENTIFIED AS BLACK BY 1432 00:55:12,281 --> 00:55:14,016 HEALTH SYSTEM, THESE PATIENTS 1433 00:55:14,016 --> 00:55:15,117 HAVE TWICE THE RELATIVE 1434 00:55:15,117 --> 00:55:16,752 INCIDENCE OF DEVELOPMENT OF 1435 00:55:16,752 --> 00:55:19,054 SEPSIS, NEARLY TWICE THE 1436 00:55:19,054 --> 00:55:20,689 MORTALITY RISK. 1437 00:55:20,689 --> 00:55:21,790 NEXT SLIDE. 1438 00:55:21,790 --> 00:55:26,095 A COUPLE THINGS TO NOTE, NOT ALL 1439 00:55:26,095 --> 00:55:29,998 RACIALIZED GROUPS SHARE THE SAME 1440 00:55:29,998 --> 00:55:32,367 RISK OF SEPSIS ADVERSE OUTCOMES. 1441 00:55:32,367 --> 00:55:34,803 SO THIS CHART OVER TIME 1442 00:55:34,803 --> 00:55:39,408 DEMONSTRATES THAT CERTAIN GROUPS 1443 00:55:39,408 --> 00:55:41,477 SPECIFICALLY BLACK AND NATIVE 1444 00:55:41,477 --> 00:55:44,113 AMERICAN REGARDLESS OF GENDER 1445 00:55:44,113 --> 00:55:48,250 HAD WORSE OUTCOMES COMPARED TO 1446 00:55:48,250 --> 00:55:50,619 OTHER GROUPS, THE THING TO NOTE 1447 00:55:50,619 --> 00:55:52,054 ABOUT THIS TREND THERE SEEMS TO 1448 00:55:52,054 --> 00:55:54,790 HAVE BEEN OVER TIME SOME 1449 00:55:54,790 --> 00:55:58,861 DIFFERENCE FOR BLACK PATIENTS 1450 00:55:58,861 --> 00:56:00,596 DECREASED INCIDENCE OF MORTALITY 1451 00:56:00,596 --> 00:56:04,199 RELATIVE TO WHITE PATIENTS BUT 1452 00:56:04,199 --> 00:56:04,766 DESPITE IMPROVEMENTS IN 1453 00:56:04,766 --> 00:56:06,869 MORTALITY OVER TIME THESE 1454 00:56:06,869 --> 00:56:14,943 DISPARITIES HAVE CONTINUED. 1455 00:56:14,943 --> 00:56:16,245 NEXT SLIDE. 1456 00:56:16,245 --> 00:56:17,713 EVEN SURVIVORSHIP HAS RACIAL 1457 00:56:17,713 --> 00:56:20,983 DISPARITIES, SO BLACK PATIENTS 1458 00:56:20,983 --> 00:56:23,152 ARE AT 50% INCREASED RISK OF 1459 00:56:23,152 --> 00:56:24,686 READMISSION COMPARED TO WHITE 1460 00:56:24,686 --> 00:56:24,953 PATIENTS. 1461 00:56:24,953 --> 00:56:30,058 WHAT ARE THE THEORIES FOR THE 1462 00:56:30,058 --> 00:56:31,793 MECHANISM UNDERLYING THESE 1463 00:56:31,793 --> 00:56:32,094 DISPARITIES? 1464 00:56:32,094 --> 00:56:33,128 IN GENERAL MECHANISMS CAN BE 1465 00:56:33,128 --> 00:56:39,902 GROUPED INTO THREE MAIN BUCKETS, 1466 00:56:39,902 --> 00:56:42,838 THAT EXPLAIN RISK FACTORS TO BE 1467 00:56:42,838 --> 00:56:45,607 ASSOCIATED WITH THESE 1468 00:56:45,607 --> 00:56:45,908 DISPARITIES. 1469 00:56:45,908 --> 00:56:46,708 CHARACTERISTICS WHICH DOVETAIL 1470 00:56:46,708 --> 00:56:49,211 WELL WITH THE CONCEPT OF 1471 00:56:49,211 --> 00:56:52,047 MULTI-MORBIDITY BUT ALSO THINGS 1472 00:56:52,047 --> 00:56:53,815 SUCH AS DISEASE SEVERITY, 1473 00:56:53,815 --> 00:56:54,917 PRESENTATION, PATIENT AGE, 1474 00:56:54,917 --> 00:56:57,553 THINGS LIKE THAT, CARE DELIVERY 1475 00:56:57,553 --> 00:56:59,821 SO THE ACTUAL HEALTHCARE 1476 00:56:59,821 --> 00:57:00,389 PROCESSES THAT RESULT IN 1477 00:57:00,389 --> 00:57:04,326 IMPROVEMENT IN UP -- SEPSIS CAE 1478 00:57:04,326 --> 00:57:10,899 AND LEAD TO ERRORS THAT MIGHT 1479 00:57:10,899 --> 00:57:12,434 CULMINATE IN ADVERSE OUTCOMES, 1480 00:57:12,434 --> 00:57:13,936 AND HOSPITAL CHARACTERISTICS, 1481 00:57:13,936 --> 00:57:21,076 SIZE, PAYER GROUP, GEOGRAPHIC 1482 00:57:21,076 --> 00:57:22,211 LOCATION, OTHER IMMUTABLE 1483 00:57:22,211 --> 00:57:23,512 CHARACTERISTICS OF HOSPITAL 1484 00:57:23,512 --> 00:57:24,479 ASSOCIATED WITH DISPARITIES. 1485 00:57:24,479 --> 00:57:26,048 NEXT SLIDE. 1486 00:57:26,048 --> 00:57:28,317 THIS LOOKS AT 28 HOSPITALS THAT 1487 00:57:28,317 --> 00:57:29,751 WERE TREATING PATIENTS WITH 1488 00:57:29,751 --> 00:57:30,719 SEPSIS, I'M SORRY, WITH 1489 00:57:30,719 --> 00:57:33,155 PNEUMONIA, SOME WENT ON TO 1490 00:57:33,155 --> 00:57:33,889 DEVELOP SEPSIS. 1491 00:57:33,889 --> 00:57:37,492 AND YOU CAN SEE EACH OF THESE 1492 00:57:37,492 --> 00:57:38,160 SQUARES THERE'S DIFFERENTIAL 1493 00:57:38,160 --> 00:57:40,996 ADJUSTMENT FOR EACH OF THESE 1494 00:57:40,996 --> 00:57:45,601 KIND OF CATEGORIES, AND SO FOR 1495 00:57:45,601 --> 00:57:48,770 THE OUTCOME, YOU SEE PATIENTS 1496 00:57:48,770 --> 00:57:50,505 WHO IDENTIFY AS BLACK STILL LESS 1497 00:57:50,505 --> 00:57:54,243 LIKELY TO GET ANTIBIOTICS IN A 1498 00:57:54,243 --> 00:57:56,445 RELEVANT TIME FRAME, EVEN 1499 00:57:56,445 --> 00:57:58,080 ADJUSTING FOR COVARIATES. 1500 00:57:58,080 --> 00:57:59,514 CERTAIN OTHER MEASURES SHOWN TO 1501 00:57:59,514 --> 00:58:02,251 BE MORE ASSOCIATED WITH RISK 1502 00:58:02,251 --> 00:58:02,918 FACTORS THAN INDEPENDENTLY WITH 1503 00:58:02,918 --> 00:58:04,653 PATIENT RACE. 1504 00:58:04,653 --> 00:58:07,055 NEXT SLIDE. 1505 00:58:07,055 --> 00:58:09,258 SO, AS I ILLUSTRATED IN THE LAST 1506 00:58:09,258 --> 00:58:11,293 SLIDE SOME OF THESE 1507 00:58:11,293 --> 00:58:12,427 RELATIONSHIPS SEEM TO BE A 1508 00:58:12,427 --> 00:58:17,899 LITTLE BIT VARIABLE IN TERMS OF 1509 00:58:17,899 --> 00:58:19,234 WHETHER ADJUSTMENT IS ASSOCIATED 1510 00:58:19,234 --> 00:58:21,069 WITH RACE OR SOME ASSOCIATED 1511 00:58:21,069 --> 00:58:21,737 RISK FACTORS. 1512 00:58:21,737 --> 00:58:23,472 ONE STUDY I WAS INTERESTED IN 1513 00:58:23,472 --> 00:58:24,573 LEADING LOOKED AT THIS QUESTION 1514 00:58:24,573 --> 00:58:27,309 OF HOW WELL THESE DIFFERENT 1515 00:58:27,309 --> 00:58:29,945 PROPOSED MECHANISMS -- PROPOSED 1516 00:58:29,945 --> 00:58:33,015 RISK FACTORS ACTUALLY REPRESENT 1517 00:58:33,015 --> 00:58:34,750 MECHANISMS FOR DISPARITIES IN 1518 00:58:34,750 --> 00:58:34,983 SEPSIS. 1519 00:58:34,983 --> 00:58:36,184 NEXT SLIDE. 1520 00:58:36,184 --> 00:58:38,020 SO MY APPROACH TO ADJUST THIS 1521 00:58:38,020 --> 00:58:40,856 QUESTION WAS TO GROUP SEVERAL 1522 00:58:40,856 --> 00:58:42,958 DIFFERENT VARIABLES WITHIN THE 1523 00:58:42,958 --> 00:58:44,459 SIX DIFFERENT CATEGORIES IN 1524 00:58:44,459 --> 00:58:47,329 ORDER TO DEVELOP A METHOD TO 1525 00:58:47,329 --> 00:58:48,530 MEASURE RELATIVE IMPORTANCE OF 1526 00:58:48,530 --> 00:58:50,699 EACH OF THESE DIFFERENT 1527 00:58:50,699 --> 00:58:51,700 CATEGORIES OF RISK FACTORS. 1528 00:58:51,700 --> 00:58:54,336 AND SO YOU CAN SEE THESE RISK 1529 00:58:54,336 --> 00:58:55,737 FACTORS HERE. 1530 00:58:55,737 --> 00:58:59,675 I WON'T BELABOR THE DETAILS IN 1531 00:58:59,675 --> 00:59:02,311 PARTICULAR, BUT THE OVERALL 1532 00:59:02,311 --> 00:59:04,479 METHOD FOR SPECIMEN OF 1533 00:59:04,479 --> 00:59:08,984 CATEGORIES IS TO USE EXTERIOR 1534 00:59:08,984 --> 00:59:13,922 MATCHING SCHEME TO DEVELOP A 1535 00:59:13,922 --> 00:59:22,230 RELATIVE ESTIMATE OF IMPORTANCE 1536 00:59:22,230 --> 00:59:23,665 OF EACH CATEGORIES. 1537 00:59:23,665 --> 00:59:25,567 WE PERFORMED THIS MATCHING STUDY 1538 00:59:25,567 --> 00:59:27,402 ACROSS 27 HOSPITALS BETWEEN 1539 00:59:27,402 --> 00:59:29,604 UNIVERSITY OF PENNSYLVANIA AND 1540 00:59:29,604 --> 00:59:32,374 KAISER PERMANENTE HEALTH SYSTEM, 1541 00:59:32,374 --> 00:59:34,543 BETWEEN 2013 AND 2018, THIS IS 1542 00:59:34,543 --> 00:59:35,844 WHAT WE FOUND. 1543 00:59:35,844 --> 00:59:36,945 X-AXIS YOU SEE DIFFERENCE IN 1544 00:59:36,945 --> 00:59:39,247 HOSPITAL LENGTH OF STAY EXPIRED 1545 00:59:39,247 --> 00:59:41,216 TO WHITE PATIENTS, FOR EACH OF 1546 00:59:41,216 --> 00:59:42,851 THE DIFFERENT RACIAL GROUPS WE 1547 00:59:42,851 --> 00:59:45,921 LIST ON THE LEGEND ON THE RIGHT. 1548 00:59:45,921 --> 00:59:48,323 EACH COLOR OF THESE DOTS 1549 00:59:48,323 --> 00:59:49,391 REPRESENTS A DIFFERENT RACIAL 1550 00:59:49,391 --> 00:59:50,158 GROUP. 1551 00:59:50,158 --> 00:59:54,629 EACH ONE OF THE LINES REPRESENTS 1552 00:59:54,629 --> 00:59:56,064 A SUCCESSIVE MATCHING SEQUENCE 1553 00:59:56,064 --> 01:00:00,869 THAT THROUGH ITS DEVELOPMENT, 1554 01:00:00,869 --> 01:00:03,205 ALLOWS US TO LOOK AT LENGTH OF 1555 01:00:03,205 --> 01:00:04,973 STAY DIFFERENCES, BASED ON 1556 01:00:04,973 --> 01:00:05,741 DIFFERENT MATCHING FACTORS. 1557 01:00:05,741 --> 01:00:08,577 AND SO TWO MAIN THINGS TO TAKE 1558 01:00:08,577 --> 01:00:10,212 AWAY FROM THIS FIGURE, FIRST OF 1559 01:00:10,212 --> 01:00:11,313 WHICH IS BLACK PATIENTS ON 1560 01:00:11,313 --> 01:00:13,615 AVERAGE HAVE LONGER HOSPITAL 1561 01:00:13,615 --> 01:00:15,917 LENGTH OF STAY, ALMOST 1 1/2 1562 01:00:15,917 --> 01:00:17,552 DAYS, COMPARED TO WHITE 1563 01:00:17,552 --> 01:00:20,288 PATIENTS, LONGER THAN ANY OTHER 1564 01:00:20,288 --> 01:00:22,157 GROUP WHILE HISPANIC GROUPS HAD 1565 01:00:22,157 --> 01:00:24,993 SHORTEST HOSPITAL LENGTH OF 1566 01:00:24,993 --> 01:00:25,727 STAY. 1567 01:00:25,727 --> 01:00:27,062 WHAT'S MORE IMPORTANT FOR THE 1568 01:00:27,062 --> 01:00:28,697 PURPOSES OF THIS DISCUSSION, 1569 01:00:28,697 --> 01:00:30,899 SUCCESSIVE ADDITION OF MATCHING 1570 01:00:30,899 --> 01:00:32,768 VARIABLES DID VERY LITTLE TO 1571 01:00:32,768 --> 01:00:35,604 CHANGE THE ESTIMATED LENGTHS OF 1572 01:00:35,604 --> 01:00:37,806 STAY DIFFERENCE BETWEEN 1573 01:00:37,806 --> 01:00:41,843 DIFFERENT GROUPS, EACH OF THE 1574 01:00:41,843 --> 01:00:43,812 IDENTIFIED VARIABLE GROUPS DOES 1575 01:00:43,812 --> 01:00:46,782 RELATIVELY LITTLE IN EXPLAIN THE 1576 01:00:46,782 --> 01:00:50,419 DISPARITIES BETWEEN PATIENT 1577 01:00:50,419 --> 01:00:50,652 GROUPS. 1578 01:00:50,652 --> 01:00:51,586 NEXT SLIDE. 1579 01:00:51,586 --> 01:00:55,424 AND SO WHAT ARE FUTURE 1580 01:00:55,424 --> 01:00:59,261 DIRECTIONS FOR ELIMINATING 1581 01:00:59,261 --> 01:01:00,162 SEPSIS AND SEPSIS-RELEVANT 1582 01:01:00,162 --> 01:01:00,629 RACISM? 1583 01:01:00,629 --> 01:01:02,664 AS MENTIONED BY THE PREVIOUS 1584 01:01:02,664 --> 01:01:04,099 SPEAKER, IT'S IMPORTANT TO 1585 01:01:04,099 --> 01:01:07,702 RECOGNIZE NATURAL TRENDS IN 1586 01:01:07,702 --> 01:01:08,703 SEPSIS DISPARITIES OVERLOOKING 1587 01:01:08,703 --> 01:01:13,708 REGIONAL DIFFERENCES IN SEPSIS 1588 01:01:13,708 --> 01:01:18,180 OUTCOMES, THIS LOOKS DIFFERENT 1589 01:01:18,180 --> 01:01:18,847 DIFFERENTLY 1590 01:01:18,847 --> 01:01:20,048 FROM PREVIOUS TALK BUT SIMILAR 1591 01:01:20,048 --> 01:01:22,784 IDEA, HEAT MAP LOOKS AT CHANGE 1592 01:01:22,784 --> 01:01:23,852 IN SEPSIS-RELATED MORTALITY IN 1593 01:01:23,852 --> 01:01:25,954 EACH STATE OVER THE STUDY 1594 01:01:25,954 --> 01:01:26,688 PERIOD. 1595 01:01:26,688 --> 01:01:31,860 AND SHOWS THAT IN SOME 1596 01:01:31,860 --> 01:01:33,395 LOCATIONS, SOME LOCATIONS ARE 1597 01:01:33,395 --> 01:01:36,064 DOING BETTER IMPROVING SEPSIS 1598 01:01:36,064 --> 01:01:38,533 MORTALITY, OTHER LOCATIONS HAVE 1599 01:01:38,533 --> 01:01:40,836 ON WORSENING IN SEPSIS-RELATED 1600 01:01:40,836 --> 01:01:43,572 OUTCOMES, ALSO THIS DIFFERS BY 1601 01:01:43,572 --> 01:01:44,005 PATIENT RACE. 1602 01:01:44,005 --> 01:01:47,275 AND SO IN ADDITION TO THINKING 1603 01:01:47,275 --> 01:01:49,878 OF JUST THE FACT THAT REGIONAL 1604 01:01:49,878 --> 01:01:51,346 DIFFERENCES EXIST IT'S IMPORTANT 1605 01:01:51,346 --> 01:01:53,882 TO UNDERSTAND LOCAL CONTEXT OF 1606 01:01:53,882 --> 01:01:56,618 WHAT DETERMINES HEALTH OUTCOMES 1607 01:01:56,618 --> 01:02:01,423 AND HOW ONE NUANCED 1608 01:02:01,423 --> 01:02:06,928 UNDERSTANDING HOW MEDICAL 1609 01:02:06,928 --> 01:02:10,198 OUTCOMES CAN BE RELATED TO MORE 1610 01:02:10,198 --> 01:02:12,167 LOCAL STRUCTURAL DETERMINANTS, 1611 01:02:12,167 --> 01:02:13,401 LIKE DE FACTO SEGREGATION, WHAT 1612 01:02:13,401 --> 01:02:16,004 THAT MEANS FOR ACCESS TO 1613 01:02:16,004 --> 01:02:17,205 HIGH-QUALITY FACILITIES COULD BE 1614 01:02:17,205 --> 01:02:18,640 IMPORTANT IN UNDERSTANDING THESE 1615 01:02:18,640 --> 01:02:20,842 DIFFERENCES, YET HAS BEEN 1616 01:02:20,842 --> 01:02:24,012 UNMEASURED AND UNSTUDIED. 1617 01:02:24,012 --> 01:02:24,880 NEXT SLIDE. 1618 01:02:24,880 --> 01:02:26,314 ANOTHER IMPORTANT SIGNAL THAT 1619 01:02:26,314 --> 01:02:28,283 EXISTS ALREADY IN LITERATURE IS 1620 01:02:28,283 --> 01:02:31,786 ROLE OF POVERTY ON OUTCOMES SUCH 1621 01:02:31,786 --> 01:02:34,956 AS INFECTIOUS RISK AND SEPSIS 1622 01:02:34,956 --> 01:02:35,624 OUTCOMES. 1623 01:02:35,624 --> 01:02:38,660 AND SO STARTING TO THINK MORE IN 1624 01:02:38,660 --> 01:02:42,264 DEPTH ABOUT HOW -- WHAT THE 1625 01:02:42,264 --> 01:02:45,467 MECHANISMS FOR POVERTY ARE FROM 1626 01:02:45,467 --> 01:02:46,134 NEIGHBORHOOD AND INDIVIDUALIZED 1627 01:02:46,134 --> 01:02:48,970 LEVEL, COULD BE TREMENDOUS IN 1628 01:02:48,970 --> 01:02:50,272 STARTING TO MOVE TOWARDS 1629 01:02:50,272 --> 01:02:55,644 INTERVENTIONS THAT COULD IMPROVE 1630 01:02:55,644 --> 01:02:56,111 DISPARITIES. 1631 01:02:56,111 --> 01:02:57,412 >> TWO MINUTES REMAINING. 1632 01:02:57,412 --> 01:02:57,712 >> GREAT. 1633 01:02:57,712 --> 01:03:00,916 AND BEYOND JUST THE IDEA OF 1634 01:03:00,916 --> 01:03:04,219 POVERTY, THIS STUDY LOOKED AT 1635 01:03:04,219 --> 01:03:05,820 SEVERAL DIFFERENT STRUCTURAL 1636 01:03:05,820 --> 01:03:07,255 DETERMINANTS, HOW ASSOCIATION 1637 01:03:07,255 --> 01:03:08,924 WITH NEIGHBORHOOD LEVELS OF THE 1638 01:03:08,924 --> 01:03:10,992 POPULATION THAT IDENTIFIED AS 1639 01:03:10,992 --> 01:03:13,862 BLACK ALSO IDENTIFIED -- ALSO 1640 01:03:13,862 --> 01:03:15,830 ASSOCIATED WITH SEPSIS 1641 01:03:15,830 --> 01:03:16,531 MORTALITY. 1642 01:03:16,531 --> 01:03:19,968 AND SO MORE NUANCED THOUGHTS 1643 01:03:19,968 --> 01:03:21,937 ABOUT HOW OTHER STRUCTURAL 1644 01:03:21,937 --> 01:03:23,271 DETERMINANTS CAN IMPACT SEPSIS 1645 01:03:23,271 --> 01:03:26,308 OUTCOMES I THINK ARE WARRANTED. 1646 01:03:26,308 --> 01:03:28,843 NEXT QUESTION. 1647 01:03:28,843 --> 01:03:30,145 I MEAN NEXT SLIDE. 1648 01:03:30,145 --> 01:03:32,881 AND SO I THINK LAST STUDY, GET 1649 01:03:32,881 --> 01:03:38,954 TO THE IDEA OF RACIAL 1650 01:03:38,954 --> 01:03:40,155 DISPARITIES, IT'S IMPORTANT TO 1651 01:03:40,155 --> 01:03:41,756 THINK ABOUT HOW STRUCTURAL 1652 01:03:41,756 --> 01:03:45,427 FACTORS ON EPIC HEALTH SYSTEM 1653 01:03:45,427 --> 01:03:47,162 LEVEL CAN INFLUENCE POPULATION 1654 01:03:47,162 --> 01:03:48,229 LEVEL PRE-SEPSIS CRITICAL CARE 1655 01:03:48,229 --> 01:03:51,299 ACCESS AND TREATMENT, HOW THAT 1656 01:03:51,299 --> 01:03:54,502 MIGHT INFLUENCE SEPSIS OUTCOMES. 1657 01:03:54,502 --> 01:03:56,805 NEXT SLIDE. 1658 01:03:56,805 --> 01:03:58,540 TO SUMMARIZE, NEXT SLIDE, 1659 01:03:58,540 --> 01:03:59,941 MINORITIZED PATIENTS EXPERIENCE 1660 01:03:59,941 --> 01:04:01,943 HIGHEST INCIDENCE IN MORTALITY 1661 01:04:01,943 --> 01:04:03,678 FROM SEPSIS BUT NOT ALL 1662 01:04:03,678 --> 01:04:04,879 MINORITIZED GROUPS EXPERIENCE TO 1663 01:04:04,879 --> 01:04:06,848 SUCH AN EXTENT. 1664 01:04:06,848 --> 01:04:07,949 CLINICAL PRESENTATION 1665 01:04:07,949 --> 01:04:09,250 CHARACTERISTICS AND 1666 01:04:09,250 --> 01:04:11,586 BETWEEN-HOSPITAL CARE DELIVERY, 1667 01:04:11,586 --> 01:04:13,555 MOST STUDIES POTENTIAL 1668 01:04:13,555 --> 01:04:15,090 DETERMINANTS HAVE YET TO 1669 01:04:15,090 --> 01:04:16,558 DEMONSTRATE A MECHANISTIC TOOL. 1670 01:04:16,558 --> 01:04:21,229 THE FIELD SHOULD MOVE TOWARDS 1671 01:04:21,229 --> 01:04:27,335 MORE IN-DEPTH CHARACTERIZING 1672 01:04:27,335 --> 01:04:31,006 STRUCTURAL RACISM HOW LIVED 1673 01:04:31,006 --> 01:04:32,974 CONTEXT LEADS TO AMERICAN HEALTH 1674 01:04:32,974 --> 01:04:33,608 DISPARITIES. 1675 01:04:33,608 --> 01:04:34,042 I WELCOME QUESTIONS. 1676 01:04:34,042 --> 01:04:35,810 >> IN THE INTEREST OF TIME WE'LL 1677 01:04:35,810 --> 01:04:38,079 MOVE TO THE LAST TALK, IF THERE 1678 01:04:38,079 --> 01:04:39,748 ARE QUESTIONS YOU CAN PUT THEM 1679 01:04:39,748 --> 01:04:41,716 IN THE CHAT OR WE'LL HAVE THE 1680 01:04:41,716 --> 01:04:42,784 PANEL DISCUSSION AFTER THE LAST 1681 01:04:42,784 --> 01:04:44,552 TALK AND YOU CAN ASK YOUR 1682 01:04:44,552 --> 01:04:50,659 QUESTIONS AT THAT TIME. 1683 01:04:50,659 --> 01:04:54,529 SO FINAL TALK IS DR. JOHN 1684 01:04:54,529 --> 01:04:56,965 DONNELLLY, UNIVERSITY OF 1685 01:04:56,965 --> 01:04:57,932 MICHIGAN, SEPSIS DISPARITIES, 1686 01:04:57,932 --> 01:05:02,737 ADDRESSING USING IMPLEMENTATION 1687 01:05:02,737 --> 01:05:03,338 SCIENCE. 1688 01:05:03,338 --> 01:05:05,473 >> THANK YOU FOR HAVING ME 1689 01:05:05,473 --> 01:05:05,674 TODAY. 1690 01:05:05,674 --> 01:05:08,309 I APPRECIATE BEING HERE WITH 1691 01:05:08,309 --> 01:05:13,682 THIS EXCELLENT PANEL OF EXPERTS. 1692 01:05:13,682 --> 01:05:16,518 SO, I'LL DISCUSS OUR APPROACH TO 1693 01:05:16,518 --> 01:05:19,688 ADDRESSING SOME INSURER WITHIN 1694 01:05:19,688 --> 01:05:22,857 SEPSIS CARE USING IMPLEMENTATION 1695 01:05:22,857 --> 01:05:25,927 SCIENCE AND LINK TO HEALTH 1696 01:05:25,927 --> 01:05:28,963 EQUITY AND SEPSIS DISPARITIES. 1697 01:05:28,963 --> 01:05:31,299 FUNDING DISCLOSURES, YOU CAN SEE 1698 01:05:31,299 --> 01:05:32,067 THOSE HERE. 1699 01:05:32,067 --> 01:05:35,670 VIEWS EXPRESSED HERE ARE MINE 1700 01:05:35,670 --> 01:05:36,337 ALONE, DO NOT REPRESENT 1701 01:05:36,337 --> 01:05:38,640 DEPARTMENT OF VETERANS AFFAIRS 1702 01:05:38,640 --> 01:05:40,241 OR THE FEDERAL GOVERNMENT. 1703 01:05:40,241 --> 01:05:40,642 NEXT SLIDE PLEASE. 1704 01:05:40,642 --> 01:05:44,112 IN THE V.A. WE DO BOTTOM LINE UP 1705 01:05:44,112 --> 01:05:45,613 FRONT A LOT. 1706 01:05:45,613 --> 01:05:48,049 NIECE ARE SOME OF THE IDEAS I'D 1707 01:05:48,049 --> 01:05:50,418 LIKE TO TALK -- THESE ARE IDEAS 1708 01:05:50,418 --> 01:05:52,754 I'D LIKE TO TALK ABOUT. 1709 01:05:52,754 --> 01:05:54,289 PERHAPS WE CAN THINK ABOUT 1710 01:05:54,289 --> 01:05:56,691 SEPSIS DISPARITIES IN TERMS OF 1711 01:05:56,691 --> 01:05:58,326 UNWANTED VARIATION IN OUTCOMES, 1712 01:05:58,326 --> 01:06:01,196 CLINICAL PRACTICE, OR ACCESS TO 1713 01:06:01,196 --> 01:06:02,263 INTERVENTIONS AND/OR QUALITY 1714 01:06:02,263 --> 01:06:03,598 IMPROVEMENT PROGRAMS. 1715 01:06:03,598 --> 01:06:05,567 THIS IS IMPORTANT BECAUSE 1716 01:06:05,567 --> 01:06:06,868 IMPLEMENTATION SCIENCE OFFERS A 1717 01:06:06,868 --> 01:06:10,572 SET OF RIGOROUS THEORY DEFINED 1718 01:06:10,572 --> 01:06:11,806 STRATEGIES TO REDUCE UNWANTED 1719 01:06:11,806 --> 01:06:13,775 VARIATION AND THIS IS 1720 01:06:13,775 --> 01:06:15,210 ACCOMPLISHED BY ENHANCING UPTAKE 1721 01:06:15,210 --> 01:06:18,513 OF EVIDENCE-BASED PRACTICES OR 1722 01:06:18,513 --> 01:06:18,813 INNOVATION. 1723 01:06:18,813 --> 01:06:20,148 AND IMPORTANTLY THOUGH CARE MUST 1724 01:06:20,148 --> 01:06:22,417 BE TAKEN TO INCORPORATE HEALTH 1725 01:06:22,417 --> 01:06:23,084 EQUITY INTO THIS PROCESS, AND 1726 01:06:23,084 --> 01:06:25,153 I'LL TRY TO MAKE THE ARGUMENT 1727 01:06:25,153 --> 01:06:27,789 IT'S IMPORTANT TO DO THIS 1728 01:06:27,789 --> 01:06:31,960 THROUGHOUT THE ENTIRE PROCESS. 1729 01:06:31,960 --> 01:06:32,827 NEXT SLIDE PLEASE. 1730 01:06:32,827 --> 01:06:35,897 I WANTED TO START QUICKLY WITH A 1731 01:06:35,897 --> 01:06:38,066 FEW EXAMPLES OF POTENTIALLY 1732 01:06:38,066 --> 01:06:39,734 UNWANTED VARIATION OR SIMPLY 1733 01:06:39,734 --> 01:06:40,635 VARIATION IN OUTCOMES AND 1734 01:06:40,635 --> 01:06:46,074 CLINICAL PRACTICE. 1735 01:06:46,074 --> 01:06:47,575 NEXT SLIDE PLEASE. 1736 01:06:47,575 --> 01:06:54,182 YOU MAY HAVE SEEN THIS FIGURE A 1737 01:06:54,182 --> 01:06:55,917 MOMENT AGO, DR. MARTIN, DR. 1738 01:06:55,917 --> 01:06:56,785 MOORE'S EXCELLENT WORK. 1739 01:06:56,785 --> 01:06:58,753 I WANT TO ADD ONE MORE SMALL 1740 01:06:58,753 --> 01:07:00,989 PIECE HERE WHICH WAS WHEN WE PUT 1741 01:07:00,989 --> 01:07:03,691 TOGETHER THIS MAP WHICH IS 1742 01:07:03,691 --> 01:07:05,560 COUNTY LEVEL SEPSIS MORTALITY, 1743 01:07:05,560 --> 01:07:07,629 AGE ADJUSTED, WE USED 1744 01:07:07,629 --> 01:07:08,930 STATISTICAL METHODS FOR 1745 01:07:08,930 --> 01:07:09,264 CLUSTERING. 1746 01:07:09,264 --> 01:07:12,333 SO WHAT YOU SEE WITHIN THESE 1747 01:07:12,333 --> 01:07:13,735 DISCRETE AREAS IS STRONGLY 1748 01:07:13,735 --> 01:07:17,472 CLUSTERED AREAS OF SEPSIS 1749 01:07:17,472 --> 01:07:18,439 MORTALITY. 1750 01:07:18,439 --> 01:07:19,674 THIS IS IMPORTANT BECAUSE LIKE 1751 01:07:19,674 --> 01:07:22,210 DR. CHESLEY MENTIONED AS WELL, 1752 01:07:22,210 --> 01:07:25,580 WE CAN THINK ABOUT THIS IN 1753 01:07:25,580 --> 01:07:27,782 ADDITION TO REPRESENTING 1754 01:07:27,782 --> 01:07:31,486 COMORBIDITIES, ACCESS TO CARE, 1755 01:07:31,486 --> 01:07:31,986 ALSO PERSISTENT POVERTY. 1756 01:07:31,986 --> 01:07:36,624 IF YOU OVERLAY THIS MAP WITH 1757 01:07:36,624 --> 01:07:37,792 PERSISTENT POVERTY IT OVERLAPS 1758 01:07:37,792 --> 01:07:41,663 QUITE EXTENSIVELY. 1759 01:07:41,663 --> 01:07:43,298 NEXT SLIDE PLEASE. 1760 01:07:43,298 --> 01:07:44,933 ONE STEP FURTHER WE DID A LOT OF 1761 01:07:44,933 --> 01:07:47,235 WORK WITHIN A LARGE LONGITUDINAL 1762 01:07:47,235 --> 01:07:49,103 COHORT OF COMMUNITY DWELLING 1763 01:07:49,103 --> 01:07:49,871 ADULTS. 1764 01:07:49,871 --> 01:07:51,940 HERE WE LOOKED AT TEN-YEAR RISK 1765 01:07:51,940 --> 01:07:54,909 OF SERIOUS INFECTION AND SEPSIS. 1766 01:07:54,909 --> 01:07:57,445 WE OFTEN LOOK AT COMORBIDITIES, 1767 01:07:57,445 --> 01:07:59,080 BASELINE CHARACTERISTICS, BUT 1768 01:07:59,080 --> 01:08:05,320 FOR THIS SPECIFIC PAPER WE 1769 01:08:05,320 --> 01:08:06,087 LOOKED AT NEIGHBORHOOD 1770 01:08:06,087 --> 01:08:07,722 SOCIOSTATUS, BLOCK GROUP LEVEL. 1771 01:08:07,722 --> 01:08:10,124 SIMILAR TO WHAT DR. CHESLEY JUST 1772 01:08:10,124 --> 01:08:11,993 MENTIONED WE FOUND GENERALLY 1773 01:08:11,993 --> 01:08:15,663 LOWER RATES OF SERIOUS INFECTION 1774 01:08:15,663 --> 01:08:17,799 AND SEPSIS IN THE COMMUNITIES IN 1775 01:08:17,799 --> 01:08:19,767 THE HIGHEST -- ABOVE THE HIGHEST 1776 01:08:19,767 --> 01:08:21,536 QUARTILE AS COMPARED WITH THOSE 1777 01:08:21,536 --> 01:08:22,737 IN THE LOWEST QUARTILE. 1778 01:08:22,737 --> 01:08:25,607 AND TO TAKE THAT ONE STEP 1779 01:08:25,607 --> 01:08:26,341 FURTHER RELEVANT TO OUR 1780 01:08:26,341 --> 01:08:29,143 CONVERSATION SO WHEN WE LOOK AT 1781 01:08:29,143 --> 01:08:31,279 MEDIATION, SO MEDIATION OF THE 1782 01:08:31,279 --> 01:08:33,481 ASSOCIATION, THINGS LIKE 1783 01:08:33,481 --> 01:08:35,516 PHYSICAL WEAKNESS, INDIVIDUAL 1784 01:08:35,516 --> 01:08:38,419 INCOME, DIABETES, ALL SEEM TO BE 1785 01:08:38,419 --> 01:08:39,621 RELEVANT POTENTIAL MEDIATORS. 1786 01:08:39,621 --> 01:08:41,589 THIS SUGGESTS THESE MIGHT 1787 01:08:41,589 --> 01:08:43,892 POTENTIALLY EXPLAIN THE 1788 01:08:43,892 --> 01:08:44,192 ASSOCIATION. 1789 01:08:44,192 --> 01:08:45,426 NEXT SLIDE PLEASE. 1790 01:08:45,426 --> 01:08:47,695 SO, THE LAST TWO EXAMPLES WERE 1791 01:08:47,695 --> 01:08:49,364 CLINICAL OUTCOMES BUT THIS IS 1792 01:08:49,364 --> 01:08:52,333 WHERE I'LL SPEND MOST OF MY TIME 1793 01:08:52,333 --> 01:08:54,602 TODAY, WHICH IS ON VARIATION IN 1794 01:08:54,602 --> 01:08:55,003 CLINICAL PRACTICE. 1795 01:08:55,003 --> 01:08:56,938 ONE AREA WE'VE BEEN VERY 1796 01:08:56,938 --> 01:08:59,340 INTERESTED IN IS LOOKING AT WAYS 1797 01:08:59,340 --> 01:09:01,943 THAT IMPLEMENTATION SCIENCE 1798 01:09:01,943 --> 01:09:02,710 COULD HELP IMPROVE ANTIMICROBIAL 1799 01:09:02,710 --> 01:09:08,516 USE IN SEPSIS. 1800 01:09:08,516 --> 01:09:11,552 THIS IS VARIATION IN TIME TO 1801 01:09:11,552 --> 01:09:12,020 DELIVERY FOR VETERANS 1802 01:09:12,020 --> 01:09:14,555 HOSPITALIZED ACROSS THE V.A. 1803 01:09:14,555 --> 01:09:16,624 HEALTH SYSTEM. 1804 01:09:16,624 --> 01:09:18,159 THERE'S FAIRLY PRONOUNCED 1805 01:09:18,159 --> 01:09:20,428 VARIABILITY BUT ALSO THE MEDIAN 1806 01:09:20,428 --> 01:09:23,398 TIME TO ANTIBIOTICS INCREASED 1807 01:09:23,398 --> 01:09:26,901 OVER TIME. 1808 01:09:26,901 --> 01:09:28,102 BETWEEN 2013 AND 2018. 1809 01:09:28,102 --> 01:09:32,240 THIS IS A SPACE WE THINK 1810 01:09:32,240 --> 01:09:35,610 INFILTRATION SCIENCE COULD MAKE 1811 01:09:35,610 --> 01:09:39,147 AN IMPACT. 1812 01:09:39,147 --> 01:09:40,481 NEXT SLIDE PLEASE. 1813 01:09:40,481 --> 01:09:43,117 SO A FEW QUICK DEFINITIONS IN 1814 01:09:43,117 --> 01:09:47,055 TERMS OF IMPLEMENTATION SCIENCE 1815 01:09:47,055 --> 01:09:48,256 AND IMPLEMENTATION RESEARCH, THE 1816 01:09:48,256 --> 01:09:49,791 STUDY OF METHODS AND STRATEGIES 1817 01:09:49,791 --> 01:09:51,960 TO IMPROVE UPTAKE OF 1818 01:09:51,960 --> 01:09:53,828 EVIDENCE-BASED PRACTICES, INTO 1819 01:09:53,828 --> 01:09:54,696 REGULAR USE. 1820 01:09:54,696 --> 01:09:56,264 AND WE THINK OF IMPLEMENTATION 1821 01:09:56,264 --> 01:09:58,866 STRATEGIES WHICH ARE KEY 1822 01:09:58,866 --> 01:10:00,068 COMPONENT OF IMPLEMENTATION WORK 1823 01:10:00,068 --> 01:10:03,237 AS THE METHODS OR TECHNIQUES 1824 01:10:03,237 --> 01:10:04,339 USED TO ENHANCE ADOPTION, 1825 01:10:04,339 --> 01:10:04,973 IMPLEMENTATION, SUSTAINABILITY 1826 01:10:04,973 --> 01:10:08,042 OF A CLINICAL PROGRAM OR 1827 01:10:08,042 --> 01:10:08,309 PRACTICE. 1828 01:10:08,309 --> 01:10:10,211 PUT IT ANOTHER WAY HOW-TWO 1829 01:10:10,211 --> 01:10:11,646 COMPONENT HOW WE GET FROM A 1830 01:10:11,646 --> 01:10:17,552 PROBLEM OR GAP TO A POTENTIAL 1831 01:10:17,552 --> 01:10:17,819 SOLUTION. 1832 01:10:17,819 --> 01:10:18,987 NEXT SLIDE PLEASE. 1833 01:10:18,987 --> 01:10:23,124 SO ONE IMPORTANT COMPONENT OF 1834 01:10:23,124 --> 01:10:24,559 IMPLEMENTATION RESEARCH IS 1835 01:10:24,559 --> 01:10:25,059 THEORETICAL FRAMEWORKS. 1836 01:10:25,059 --> 01:10:26,961 SO WE USE A LOT OF FRAMEWORKS 1837 01:10:26,961 --> 01:10:29,597 BUT THIS ONE IN PARTICULAR HAS 1838 01:10:29,597 --> 01:10:31,899 BEEN ESPECIALLY -- WHAT YOU SEE 1839 01:10:31,899 --> 01:10:33,434 HERE IS A GRAPHIC REPRESENTING 1840 01:10:33,434 --> 01:10:37,271 THE V.A. QUALITY ENHANCEMENT 1841 01:10:37,271 --> 01:10:38,806 RESEARCH INITIATIVE 1842 01:10:38,806 --> 01:10:40,108 IMPLEMENTATION ROAD MAP, THAT 1843 01:10:40,108 --> 01:10:40,942 WALKS THROUGH DIFFERENT 1844 01:10:40,942 --> 01:10:41,676 ACTIVITIES AND IMPORTANT 1845 01:10:41,676 --> 01:10:44,145 QUESTIONS WE NEED TO BE ASKING 1846 01:10:44,145 --> 01:10:46,681 ACROSS THREE PHASES OF 1847 01:10:46,681 --> 01:10:48,116 IMPLEMENTATION WHICH ARE 1848 01:10:48,116 --> 01:10:48,549 PRE-IMPLEMENTATION, 1849 01:10:48,549 --> 01:10:49,183 IMPLEMENTATION, AND 1850 01:10:49,183 --> 01:10:50,651 SUSTAINABILITY. 1851 01:10:50,651 --> 01:10:52,887 I WON'T GO INTO DETAIL HERE BUT 1852 01:10:52,887 --> 01:10:55,423 REALLY THE GENERAL IDEA IS JUST 1853 01:10:55,423 --> 01:10:57,158 THAT WITHIN EACH OF THESE BINS 1854 01:10:57,158 --> 01:11:00,361 WE HAVE DIFFERENT QUESTIONS WE 1855 01:11:00,361 --> 01:11:01,963 ASK AND DIFFERENT ACTIVITIES. 1856 01:11:01,963 --> 01:11:05,166 I'LL SPEND MOST OF MY TIME ON 1857 01:11:05,166 --> 01:11:06,234 THIS PRE-IMPLEMENTATION AND 1858 01:11:06,234 --> 01:11:06,834 IMPLEMENTATION PHASE, SIMPLY 1859 01:11:06,834 --> 01:11:08,136 BECAUSE THIS IS AN AREA WHERE 1860 01:11:08,136 --> 01:11:11,406 THERE'S BEEN QUITE A BIT OF 1861 01:11:11,406 --> 01:11:12,807 RECENT INTEREST AND RESEARCH IN 1862 01:11:12,807 --> 01:11:16,744 TERMS OF HOW WE INTERPRET HEALTH 1863 01:11:16,744 --> 01:11:21,883 EQUITY, WHICH COULD BE RELEVANT 1864 01:11:21,883 --> 01:11:22,850 IN ADDRESSING SEPSIS 1865 01:11:22,850 --> 01:11:23,151 DISPARITIES. 1866 01:11:23,151 --> 01:11:24,085 I'LL SPEND SOME TIME HERE. 1867 01:11:24,085 --> 01:11:28,790 THIS IS AN IMPORTANT COMPONENT 1868 01:11:28,790 --> 01:11:34,796 OF THE QUERI IMPLEMENTATION ROAD 1869 01:11:34,796 --> 01:11:35,329 MAP. 1870 01:11:35,329 --> 01:11:37,432 WE'RE HERE PLANNING FOR 1871 01:11:37,432 --> 01:11:37,965 IMPLEMENTATION. 1872 01:11:37,965 --> 01:11:40,735 AND SO YOU SEE A STEPPED 1873 01:11:40,735 --> 01:11:43,671 APPROACH TO GETTING FROM A 1874 01:11:43,671 --> 01:11:47,308 CLINICAL PROBLEM OR OBSERVED GAP 1875 01:11:47,308 --> 01:11:48,943 TO POTENTIAL SOLUTION, THE 1876 01:11:48,943 --> 01:11:49,911 IMPLEMENTATION STRATEGY. 1877 01:11:49,911 --> 01:11:51,913 STARTING ON THE FAR LEFT, OUR 1878 01:11:51,913 --> 01:11:55,049 FIRST STEP IS TO ASSESS PRACTICE 1879 01:11:55,049 --> 01:11:56,918 GAPS, TO UNDERSTAND WHERE 1880 01:11:56,918 --> 01:11:58,252 CURRENTS PRACTICE IS. 1881 01:11:58,252 --> 01:12:01,622 THE GRAPH I SHOWED WITH 1882 01:12:01,622 --> 01:12:02,490 VARIATION IN ANTIBIOTIC TIMES 1883 01:12:02,490 --> 01:12:05,026 WOULD BE AN EXAMPLE OF THIS. 1884 01:12:05,026 --> 01:12:07,628 THIS IS WHERE THERE MAY BE A GAP 1885 01:12:07,628 --> 01:12:09,597 WE CAN START TO ADDRESS. 1886 01:12:09,597 --> 01:12:12,467 KIND OF TWO BOXES TO THE RIGHT, 1887 01:12:12,467 --> 01:12:16,704 SO THIS IS WHERE WE'LL START 1888 01:12:16,704 --> 01:12:19,373 THINKING THROUGH WHAT POTENTIAL 1889 01:12:19,373 --> 01:12:20,374 INTERVENTIONS, SOLUTIONS, AND 1890 01:12:20,374 --> 01:12:23,211 INNOVATIONS MIGHT HELP ADDRESS 1891 01:12:23,211 --> 01:12:24,745 THIS IMPORTANT GAP. 1892 01:12:24,745 --> 01:12:26,814 STEP 4 IS A KEY ONE AS WELL. 1893 01:12:26,814 --> 01:12:29,784 THIS IS WHERE WE USE THEORETICAL 1894 01:12:29,784 --> 01:12:32,286 FRAMEWORKS TO IDENTIFY BARRIERS 1895 01:12:32,286 --> 01:12:34,055 AND FACILITATORS TO 1896 01:12:34,055 --> 01:12:35,156 IMPLEMENTATION OF INTERVENTION 1897 01:12:35,156 --> 01:12:38,693 OR PRACTICE THAT WE JUST 1898 01:12:38,693 --> 01:12:38,993 IDENTIFIED. 1899 01:12:38,993 --> 01:12:42,163 SO THIS IS REALLY KIND OF THE 1900 01:12:42,163 --> 01:12:43,264 BULK OF THE PRE-IMPLEMENTATION 1901 01:12:43,264 --> 01:12:44,699 PROCESS, AND THIS IS WHERE WE 1902 01:12:44,699 --> 01:12:46,534 REALLY TRY TO UNDERSTAND 1903 01:12:46,534 --> 01:12:47,001 CONTEXT. 1904 01:12:47,001 --> 01:12:49,003 SO WE'RE TRYING TO IMPLEMENT 1905 01:12:49,003 --> 01:12:50,271 SOMETHING, WHAT IS THE CONTEXT 1906 01:12:50,271 --> 01:12:52,974 THAT WE'RE WORKING IN. 1907 01:12:52,974 --> 01:12:54,742 SO IT'S JUMPING DOWN TO STEP 6, 1908 01:12:54,742 --> 01:12:58,179 HERE IS WHERE WE USE THEORY 1909 01:12:58,179 --> 01:12:59,680 AGAIN TO DESIGN IMPLEMENTATION 1910 01:12:59,680 --> 01:13:01,115 STRATEGY SO WE WANT OUR 1911 01:13:01,115 --> 01:13:02,750 STRATEGIES IN GENERAL TO BE 1912 01:13:02,750 --> 01:13:05,386 LINKED TO BARRIERS WE WANT TO 1913 01:13:05,386 --> 01:13:08,055 OVERCOME, HELPING TO IMPROVE OR 1914 01:13:08,055 --> 01:13:08,723 FACILITATE IMPLEMENTATION WITHIN 1915 01:13:08,723 --> 01:13:12,493 THE CONTEXT THAT WE'RE WORKING. 1916 01:13:12,493 --> 01:13:14,996 AND SO REALLY TO SUMMARIZE, THIS 1917 01:13:14,996 --> 01:13:16,964 IS A HELPFUL KIND OF STEPPED 1918 01:13:16,964 --> 01:13:18,599 APPROACH TO GETTING TO 1919 01:13:18,599 --> 01:13:21,769 IMPLEMENTATION STRATEGY. 1920 01:13:21,769 --> 01:13:22,770 NEXT SLIDE PLEASE. 1921 01:13:22,770 --> 01:13:26,741 AND JUST TO DRIVE THIS HOME I 1922 01:13:26,741 --> 01:13:29,544 WANTED TO TALK THROUGH THE 1923 01:13:29,544 --> 01:13:31,279 ANTIBIOTIC EXAMPLE, IN MORE 1924 01:13:31,279 --> 01:13:31,512 DETAIL. 1925 01:13:31,512 --> 01:13:33,281 SO HOW WE'VE THOUGHT ABOUT THIS 1926 01:13:33,281 --> 01:13:36,017 IN TERMS OF ANTIBIOTICS FOR 1927 01:13:36,017 --> 01:13:38,753 SEPSIS IS THAT WE WANT TO START 1928 01:13:38,753 --> 01:13:41,022 FROM A RECOMMENDATION WITH 1929 01:13:41,022 --> 01:13:41,689 FAIRLY STRONG EVIDENCE. 1930 01:13:41,689 --> 01:13:44,825 SO HERE ON THE LEFT WE SEE THE 1931 01:13:44,825 --> 01:13:53,467 REVISED RECOMMENDATION IN THE 1932 01:13:53,467 --> 01:13:55,369 SURVIVING SEPSIS TWAIN 2021 1933 01:13:55,369 --> 01:13:58,005 GUIDELINES, THE RECOMMENDATION 1934 01:13:58,005 --> 01:13:59,207 IS NOW STRATIFIED BASED ON 1935 01:13:59,207 --> 01:14:00,641 PATIENT SEVERITY, KIND OF WHAT 1936 01:14:00,641 --> 01:14:02,610 THE PRESENTATION LOOKS LIKE. 1937 01:14:02,610 --> 01:14:08,649 HERE THE GOAL FOR PATIENTS WHERE 1938 01:14:08,649 --> 01:14:10,284 SEPSIS IS DEFINITE OR PROBABLE 1939 01:14:10,284 --> 01:14:11,485 OR SHOCK IS PRESENT 1940 01:14:11,485 --> 01:14:12,353 RECOMMENDATION IS ANTIBIOTICS 1941 01:14:12,353 --> 01:14:14,555 WITHIN ONE HOUR. 1942 01:14:14,555 --> 01:14:16,390 OTHERWISE, RECOMMENDATION WOULD 1943 01:14:16,390 --> 01:14:18,359 BE WITHIN THREE HOURS IF THERE'S 1944 01:14:18,359 --> 01:14:19,126 SOME KIND OF LINGERING 1945 01:14:19,126 --> 01:14:20,561 CONCERNING FOR AN INFECTION. 1946 01:14:20,561 --> 01:14:21,796 BUT THIS DOESN'T NECESSARILY GET 1947 01:14:21,796 --> 01:14:25,366 US TO THE POINT OF PRACTICES. 1948 01:14:25,366 --> 01:14:27,001 SO BASICALLY WE THOUGHT THROUGH 1949 01:14:27,001 --> 01:14:29,103 WHAT ARE POTENTIAL PRACTICES 1950 01:14:29,103 --> 01:14:30,638 THAT MIGHT BE IMPLEMENTABLE TO 1951 01:14:30,638 --> 01:14:32,974 HELP ADDRESS THIS. 1952 01:14:32,974 --> 01:14:34,875 SO WE WON'T GO INTO DETAIL BUT 1953 01:14:34,875 --> 01:14:37,311 IN TERMS OF SCREENING WE NEED A 1954 01:14:37,311 --> 01:14:39,146 WAY TO IDENTIFY PATIENTS WHO 1955 01:14:39,146 --> 01:14:40,681 HAVE INFECTION AND SEPSIS, THERE 1956 01:14:40,681 --> 01:14:43,951 NEEDS TO BE REPEAT ASSESSMENT OF 1957 01:14:43,951 --> 01:14:46,621 CLINICAL CRITERIA, KIND OF ONCE 1958 01:14:46,621 --> 01:14:49,090 THE PATIENT HAS PRESENTED, 1959 01:14:49,090 --> 01:14:51,425 POTENTIALLY MOST IMPORTANTLY FOR 1960 01:14:51,425 --> 01:14:52,827 PURPOSES HERE PRESCRIBE 1961 01:14:52,827 --> 01:14:55,896 ANTIBIOTICS RAPIDLY FOR PATIENTS 1962 01:14:55,896 --> 01:14:58,199 WITH SHOCK OR OVERT ORGAN 1963 01:14:58,199 --> 01:14:59,400 FAILURE, A TRACTABLE PRACTICE WE 1964 01:14:59,400 --> 01:15:01,369 CAN LOOK AT. 1965 01:15:01,369 --> 01:15:04,538 AND THEN IF INDICATED WE WANT 1966 01:15:04,538 --> 01:15:05,106 ANTIBIOTICS WITH APPROPRIATE 1967 01:15:05,106 --> 01:15:07,275 COVERAGE, AND THEN IT COULD BE 1968 01:15:07,275 --> 01:15:08,476 POSSIBLE TO DEFER ANTIBIOTICS 1969 01:15:08,476 --> 01:15:10,011 FOR PATIENTS WITH UNCLEAR 1970 01:15:10,011 --> 01:15:13,848 DIAGNOSES WHILE WE COMPLETE THE 1971 01:15:13,848 --> 01:15:17,451 ASSESSMENT. 1972 01:15:17,451 --> 01:15:19,654 NEXT SLIDE PLEASE. 1973 01:15:19,654 --> 01:15:23,057 THE WAY WE'VE THOUGHT THROUGH 1974 01:15:23,057 --> 01:15:25,793 THIS, LEFT-HAND SIDE PRACTICE 1975 01:15:25,793 --> 01:15:26,661 ASSESSMENT, QUANTITATIVE EXAMPLE 1976 01:15:26,661 --> 01:15:28,663 I DESCRIBE AT THE BEGINNING, 1977 01:15:28,663 --> 01:15:31,065 LOOKING AT VARIATION, AN 1978 01:15:31,065 --> 01:15:32,600 EXAMPLE, BUT WE DO NEED TO 1979 01:15:32,600 --> 01:15:34,702 EXPAND UPON QUALITATIVE WORK AS 1980 01:15:34,702 --> 01:15:34,902 WELL. 1981 01:15:34,902 --> 01:15:37,405 SO WE WANT TO DO INTERVIEWS, 1982 01:15:37,405 --> 01:15:39,740 SURVEYS TO BETTER UNDERSTAND 1983 01:15:39,740 --> 01:15:41,709 BARRIERS AND FACILITATORS. 1984 01:15:41,709 --> 01:15:44,979 AND SPECIFICALLY RELEVANT TO 1985 01:15:44,979 --> 01:15:46,180 TAILORING ANTIBIOTICS, SO 1986 01:15:46,180 --> 01:15:48,015 TAILORING ANTIBIOTICS BASED ON 1987 01:15:48,015 --> 01:15:48,649 PATIENT SEVERITY. 1988 01:15:48,649 --> 01:15:51,419 AND SO JUST A FEW OF THE 1989 01:15:51,419 --> 01:15:51,886 POSSIBLE BARRIERS AND 1990 01:15:51,886 --> 01:15:54,722 FACILITATORS WE CAME UP WITH, IN 1991 01:15:54,722 --> 01:15:57,892 EARLY PILOT WORK, IS POTENTIAL 1992 01:15:57,892 --> 01:15:59,860 LACK OF FEEDBACK, SOME EMERGENCY 1993 01:15:59,860 --> 01:16:02,396 DEPARTMENT SPECIFIC ISSUES LIKE 1994 01:16:02,396 --> 01:16:06,600 OVERCROWDING, AS WELL AS 1995 01:16:06,600 --> 01:16:08,035 WORKFORCE-RELATED ISSUES, MAYBE 1996 01:16:08,035 --> 01:16:09,770 MORE ACCURATELY WORK FLOW 1997 01:16:09,770 --> 01:16:14,408 RELATED ISSUES, WAYS TO LEVERAGE 1998 01:16:14,408 --> 01:16:15,076 NURSING RESOURCES TO IMPROVE 1999 01:16:15,076 --> 01:16:15,910 ANTIBIOTIC USE. 2000 01:16:15,910 --> 01:16:18,346 THIS IS WHERE WE MATCH THESE 2001 01:16:18,346 --> 01:16:20,081 IDEAS WITH SOME POSSIBLE 2002 01:16:20,081 --> 01:16:22,283 STRATEGIES, POTENTIALLY MOST 2003 01:16:22,283 --> 01:16:23,484 IMPORTANT ON TOP, THINKING 2004 01:16:23,484 --> 01:16:24,452 THROUGH CREATIVE WAYS TO DELIVER 2005 01:16:24,452 --> 01:16:30,691 FEEDBACK IN A WAY THAT'S 2006 01:16:30,691 --> 01:16:31,659 MEANINGFUL TO CLINICIANS. 2007 01:16:31,659 --> 01:16:34,929 THE LAST MINUTE OR TWO HERE, ON 2008 01:16:34,929 --> 01:16:36,831 THIS ISSUE OF HEALTH EQUITY. 2009 01:16:36,831 --> 01:16:39,100 SO THE TWO PAPERS ON THE BOTTOM 2010 01:16:39,100 --> 01:16:42,069 LEFT, BOTH OF THESE REALLY MADE 2011 01:16:42,069 --> 01:16:43,604 A VERY STRONG CASE FOR 2012 01:16:43,604 --> 01:16:45,439 INCORPORATING HEALTH EQUITY INTO 2013 01:16:45,439 --> 01:16:49,076 THE IMPLEMENTATION PROCESS. 2014 01:16:49,076 --> 01:16:50,378 JUST THE KEY TAKEHOME MESSAGE 2015 01:16:50,378 --> 01:16:52,246 HERE WE NEED TO INCORPORATE 2016 01:16:52,246 --> 01:16:54,415 HEALTH EQUITY FROM OUTSET AND 2017 01:16:54,415 --> 01:16:55,316 WITHIN ALL IMPLEMENTATION 2018 01:16:55,316 --> 01:16:56,717 ACTIVITIES AND PHASES. 2019 01:16:56,717 --> 01:16:58,386 I THINK ONE OF THE MOST 2020 01:16:58,386 --> 01:16:59,320 IMPORTANT IS LIKELY THE ONE AT 2021 01:16:59,320 --> 01:17:02,456 THE TOP OF THE TABLE ON THE 2022 01:17:02,456 --> 01:17:03,324 RIGHT, ENGAGING INTERESTED 2023 01:17:03,324 --> 01:17:05,092 PARTIES AND/OR STAKEHOLDERS IN 2024 01:17:05,092 --> 01:17:08,462 THIS PROCESS FROM THE BEGINNING 2025 01:17:08,462 --> 01:17:10,965 AND MAKING SURE WE'RE TRYING TO 2026 01:17:10,965 --> 01:17:16,937 ENGAGE THEM THROUGHOUT THE 2027 01:17:16,937 --> 01:17:18,139 PROCESS AS WELL. 2028 01:17:18,139 --> 01:17:19,306 IT'S IMPORTANT TO LAY GROUND 2029 01:17:19,306 --> 01:17:20,708 WORK EARLY THAT HEALTH EQUITY IS 2030 01:17:20,708 --> 01:17:22,843 IMPORTANT AND WE WANT TO 2031 01:17:22,843 --> 01:17:27,114 ACTIVELY INCORPORATE THIS 2032 01:17:27,114 --> 01:17:27,915 THROUGHOUT IMPLEMENTATION AS 2033 01:17:27,915 --> 01:17:28,215 WELL. 2034 01:17:28,215 --> 01:17:30,951 NEXT SLIDE PLEASE. 2035 01:17:30,951 --> 01:17:32,920 SO LASTLY THAT IDEA OF 2036 01:17:32,920 --> 01:17:36,957 INCORPORATING HEALTH EQUITY INTO 2037 01:17:36,957 --> 01:17:38,058 IMPLEMENTATION IS FAIRLY BIG 2038 01:17:38,058 --> 01:17:39,927 PICTURE SO ONE EXAMPLE TRYING TO 2039 01:17:39,927 --> 01:17:42,029 MAKE THIS WAY MORE 2040 01:17:42,029 --> 01:17:43,764 UNDERSTANDABLE AND ACTIONABLE IS 2041 01:17:43,764 --> 01:17:47,902 THAT THE HEALTH EQUITY 2042 01:17:47,902 --> 01:17:48,502 IMPLEMENTATION FRAMEWORK, SO 2043 01:17:48,502 --> 01:17:51,205 WOODWARD ET AL. PRESENTED THIS A 2044 01:17:51,205 --> 01:17:52,840 FEW YEARS AGO, TO TAKE AN 2045 01:17:52,840 --> 01:17:55,042 EXISTING FRAMEWORK WHICH HELPS 2046 01:17:55,042 --> 01:17:56,444 US UNDERSTAND BARRIERS AROUND 2047 01:17:56,444 --> 01:17:57,445 FACILITATORS AND ADD DOMAINS 2048 01:17:57,445 --> 01:18:00,080 THAT ARE RELEVANT TO HEALTH 2049 01:18:00,080 --> 01:18:01,148 EQUITY. 2050 01:18:01,148 --> 01:18:03,117 THIS IS DEFINITELY PROBLEM OR 2051 01:18:03,117 --> 01:18:04,452 CONDITION SPECIFIC OR PROJECT 2052 01:18:04,452 --> 01:18:04,718 SPECIFIC. 2053 01:18:04,718 --> 01:18:08,956 BUT THIS IS A PROCESS WE CAN DO 2054 01:18:08,956 --> 01:18:11,325 THAT REALLY HELPS TO ACTIVELY 2055 01:18:11,325 --> 01:18:12,526 INCORPORATE HEALTH EQUITY. 2056 01:18:12,526 --> 01:18:14,728 AND SO JUST THE LAST FINAL 2057 01:18:14,728 --> 01:18:17,598 POINT, SO REALLY THE MAIN IDEA 2058 01:18:17,598 --> 01:18:20,968 HERE WITH THIS FRAMEWORK TO DO 2059 01:18:20,968 --> 01:18:22,937 TWO THINGS SIMULTANEOUSLY, SO TO 2060 01:18:22,937 --> 01:18:24,138 ACHIEVE SUCCESSFUL 2061 01:18:24,138 --> 01:18:25,439 IMPLEMENTATION BUT ALSO TO 2062 01:18:25,439 --> 01:18:26,774 ACTIVELY WORK TO IMPROVE HEALTH 2063 01:18:26,774 --> 01:18:27,107 EQUITY. 2064 01:18:27,107 --> 01:18:30,478 TO PUT THAT PART SLIGHTLY 2065 01:18:30,478 --> 01:18:32,246 DIFFERENTLY, ACTIVELY WORK TO 2066 01:18:32,246 --> 01:18:37,384 IMPROVE SEPSIS OR HEALTH 2067 01:18:37,384 --> 01:18:39,320 DISPARITIES. 2068 01:18:39,320 --> 01:18:40,888 NEXT SLIDE PLEASE. 2069 01:18:40,888 --> 01:18:43,524 SO JUST VERY QUICK FINAL 2070 01:18:43,524 --> 01:18:45,593 CONCLUSIONS, SO LIKE I MENTIONED 2071 01:18:45,593 --> 01:18:48,562 WE CAN REFRAME THE SEPSIS 2072 01:18:48,562 --> 01:18:50,064 DISPARITY QUESTION POTENTIALLY, 2073 01:18:50,064 --> 01:18:51,599 IN TERMS OF UNWANTED VARIATION 2074 01:18:51,599 --> 01:18:55,436 IN SEPSIS RISK AND OUTCOMES AS 2075 01:18:55,436 --> 01:18:57,938 WELL AS CLINICAL PRACTICE, AND 2076 01:18:57,938 --> 01:18:59,306 WE HAVE POTENTIALLY EFFECTIVE 2077 01:18:59,306 --> 01:19:01,475 TOOLS TO HELP REDUCE UNWANTED 2078 01:19:01,475 --> 01:19:03,944 VARIATION, IMPROVE CARE FOR ALL 2079 01:19:03,944 --> 01:19:04,311 SIMULTANEOUSLY. 2080 01:19:04,311 --> 01:19:07,715 BUT IT'S IMPORTANT TO USE THEORY 2081 01:19:07,715 --> 01:19:08,916 TO DERIVE THESE IMPLICATION 2082 01:19:08,916 --> 01:19:11,552 STRATEGIES, AND LASTLY LIKE I 2083 01:19:11,552 --> 01:19:13,921 MENTIONED, SO WE WANT TO FOCUS 2084 01:19:13,921 --> 01:19:16,357 ON TWO GOALS AT THE SAME TIME 2085 01:19:16,357 --> 01:19:17,992 WHICH IS ACHIEVING SUCCESSFUL 2086 01:19:17,992 --> 01:19:18,692 IMPLEMENTATION OF EVIDENCE-BASED 2087 01:19:18,692 --> 01:19:21,061 PRACTICES THAT WILL HELP IMPROVE 2088 01:19:21,061 --> 01:19:23,797 SEPSIS CARE, AND ALSO ENSURING 2089 01:19:23,797 --> 01:19:26,000 THAT DISPARITIES ARE 2090 01:19:26,000 --> 01:19:27,735 SUCCESSFULLY ADDRESSED AS WELL. 2091 01:19:27,735 --> 01:19:30,371 THANK YOU SO MUCH, AND I GUESS 2092 01:19:30,371 --> 01:19:30,771 NEXT SLIDE PLEASE. 2093 01:19:30,771 --> 01:19:32,540 THANK YOU SO MUCH FOR YOUR TIME 2094 01:19:32,540 --> 01:19:34,074 AND HAPPY TO TAKE ANY QUESTIONS 2095 01:19:34,074 --> 01:19:41,415 IF THERE'S TIME AVAILABLE. 2096 01:19:41,415 --> 01:19:44,818 >> ARE THERE QUESTIONS FOR DR. 2097 01:19:44,818 --> 01:19:51,058 DONNELLLY? 2098 01:19:51,058 --> 01:19:55,763 THIS IS A PERFECT SEGUE INTO THE 2099 01:19:55,763 --> 01:19:59,133 PANEL DISCUSSION, DR. ASHANNA 2100 01:19:59,133 --> 01:19:59,867 WILL MODERATE THAT SESSION. 2101 01:19:59,867 --> 01:20:00,568 >> THANKS. 2102 01:20:00,568 --> 01:20:11,078 WE INVITE ALL FOUR SPEAKERS TO 2103 01:20:13,247 --> 01:20:14,281 COME ON VIDEO. 2104 01:20:14,281 --> 01:20:17,885 THANK YOU FOR YOUR TALKS. 2105 01:20:17,885 --> 01:20:19,086 YOU MAY DROP ADDITION EQUAL 2106 01:20:19,086 --> 01:20:21,589 QUESTIONS IN THE CHAT. 2107 01:20:21,589 --> 01:20:23,023 FIRST FOR DOCTORS RUDD AND 2108 01:20:23,023 --> 01:20:23,257 MARTIN. 2109 01:20:23,257 --> 01:20:32,299 THANK YOU FOR YOUR TALKS. 2110 01:20:32,299 --> 01:20:39,106 A LITTLE BIT OF BACKGROUND, THIS 2111 01:20:39,106 --> 01:20:41,175 CLIFF ANALOGY WAS PROPOSED, 2112 01:20:41,175 --> 01:20:42,710 LEVELS OF HEALTH PREVENTION, SHE 2113 01:20:42,710 --> 01:20:44,044 DESCRIBED PEOPLE WALKING TOWARDS 2114 01:20:44,044 --> 01:20:46,780 THE EDGE OF A CLIFF AND FALLING 2115 01:20:46,780 --> 01:20:48,182 OFF THE BOTTOM WHERE AN 2116 01:20:48,182 --> 01:20:51,251 AMBULANCE IS WAITING TO RESCUE 2117 01:20:51,251 --> 01:20:52,152 THEM. 2118 01:20:52,152 --> 01:20:55,656 THE AMBULANCE IS REPRESENTING 2119 01:20:55,656 --> 01:20:57,925 TERTIARY PREVENTION, SECONDARY 2120 01:20:57,925 --> 01:20:58,726 PREVENTION WOULD ININVOLVE 2121 01:20:58,726 --> 01:20:59,326 INSTALLING SAFETY NETS BEFORE 2122 01:20:59,326 --> 01:21:04,832 THEY FALL TO THE GROUND. 2123 01:21:04,832 --> 01:21:06,467 PRIMARY PREVENTION WOULD INVOLVE 2124 01:21:06,467 --> 01:21:08,969 ENACTING A BARRIER SO THEY DON'T 2125 01:21:08,969 --> 01:21:09,236 FALL. 2126 01:21:09,236 --> 01:21:16,343 THIS IS PROVOCATIVE QUESTION BUT 2127 01:21:16,343 --> 01:21:24,952 WHAT WE DO IS A ANALOGOUS TO TE 2128 01:21:24,952 --> 01:21:26,186 AMBULANCE, PERHAPS THEY ARE 2129 01:21:26,186 --> 01:21:27,621 UNABLE TO MANAGE BECAUSE THEY 2130 01:21:27,621 --> 01:21:29,156 DON'T HAVE GOOD OUTPATIENT 2131 01:21:29,156 --> 01:21:30,691 HEALTH CARE ACCESS IN THEIR 2132 01:21:30,691 --> 01:21:31,659 COMMUNITIES. 2133 01:21:31,659 --> 01:21:34,628 WHEN THEY BECOME CRITICALLY ILL 2134 01:21:34,628 --> 01:21:37,264 WE MEET THEM. 2135 01:21:37,264 --> 01:21:40,567 WHAT ARE THE ADVANTAGES TO THIS 2136 01:21:40,567 --> 01:21:42,069 APPROACH FOCUSING ON SEPSIS IN 2137 01:21:42,069 --> 01:21:44,505 THE ICU AND WHAT MAY BE 2138 01:21:44,505 --> 01:21:52,813 DISADVANTAGES AND HOW MIGHT WE 2139 01:21:52,813 --> 01:21:54,548 ADDRESS THOSE? 2140 01:21:54,548 --> 01:21:56,784 DO YOU WANT TO START, KRISTINA? 2141 01:21:56,784 --> 01:21:57,217 >> SURE. 2142 01:21:57,217 --> 01:22:00,688 I CAN THINK OF ALL SORTS OF 2143 01:22:00,688 --> 01:22:01,021 DISADVANTAGES. 2144 01:22:01,021 --> 01:22:02,322 I'LL START THERE. 2145 01:22:02,322 --> 01:22:06,060 I CAN THINK ABOUT THE ADVANTAGES 2146 01:22:06,060 --> 01:22:07,828 AS WELL. 2147 01:22:07,828 --> 01:22:10,864 FOR ME, IT'S THE COMBINATION OF 2148 01:22:10,864 --> 01:22:12,966 THE SHEER NUMBERS OF INCIDENT 2149 01:22:12,966 --> 01:22:16,770 CASES OF SEPSIS EACH YEAR. 2150 01:22:16,770 --> 01:22:21,375 GLOBALLY IF WE CONTINUE TO ALLOW 2151 01:22:21,375 --> 01:22:23,010 50 MILLION CASES OF SEPSIS, LIKE 2152 01:22:23,010 --> 01:22:23,811 SOME OF THOSE PEOPLE AREN'T 2153 01:22:23,811 --> 01:22:26,380 GOING TO BE PICKED UP BY A GOOD 2154 01:22:26,380 --> 01:22:26,947 AMBULANCE, RIGHT? 2155 01:22:26,947 --> 01:22:31,885 THEY ARE NOT GOING TO -- WE CAN 2156 01:22:31,885 --> 01:22:33,420 STUDY TILL THE COWS COME HOME 2157 01:22:33,420 --> 01:22:38,792 BUT WHAT TO DO ONCE PEOPLE HAVE 2158 01:22:38,792 --> 01:22:40,294 SEPSIS, BUT WE'RE NOT GOING TO 2159 01:22:40,294 --> 01:22:41,962 BE ABLE TO GIVE EVERY ONE OF THE 2160 01:22:41,962 --> 01:22:44,031 50 MILLION PEOPLE THE BEST 2161 01:22:44,031 --> 01:22:44,798 EVIDENCE-BASED CARE. 2162 01:22:44,798 --> 01:22:48,635 SO I THINK WE DO NEED TO 2163 01:22:48,635 --> 01:22:50,370 CONTINUE TO IMPROVE THAT 2164 01:22:50,370 --> 01:22:52,573 TERTIARY LEVEL OF LIKE BUILD OUR 2165 01:22:52,573 --> 01:22:53,974 EVIDENCE BASE, KNOW WHAT WE CAN 2166 01:22:53,974 --> 01:22:55,743 DO TO IMPROVE CARE FOR PEOPLE 2167 01:22:55,743 --> 01:22:58,345 ONCE THEY HAVE SEPSIS, WE'VE GOT 2168 01:22:58,345 --> 01:22:59,580 TO SLOW THE VOLUME OF PEOPLE 2169 01:22:59,580 --> 01:23:03,317 SHOWING UP TO THE HOSPITAL WITH 2170 01:23:03,317 --> 01:23:03,550 SEPSIS. 2171 01:23:03,550 --> 01:23:06,687 I THINK THAT'S ONE. 2172 01:23:06,687 --> 01:23:08,789 AND THEN TWO IS I THINK IT'S THE 2173 01:23:08,789 --> 01:23:10,758 RIGHT THING TO DO AS HEALTHCARE 2174 01:23:10,758 --> 01:23:12,626 PROVIDERS TO WANT PEOPLE TO BE 2175 01:23:12,626 --> 01:23:13,927 HEALTHY AND NOT WAIT UNTIL THEY 2176 01:23:13,927 --> 01:23:14,595 ARE SICK. 2177 01:23:14,595 --> 01:23:15,996 AND SO I THINK THERE'S ALL SORTS 2178 01:23:15,996 --> 01:23:18,732 OF THINGS WE COULD BE DOING FOR 2179 01:23:18,732 --> 01:23:19,500 PRIMARY AND SECONDARY 2180 01:23:19,500 --> 01:23:20,968 PREVENTION, I'LL PAUSE AND LET 2181 01:23:20,968 --> 01:23:23,170 OTHERS MAYBE START THAT PIECE OF 2182 01:23:23,170 --> 01:23:24,538 THE CONVERSATION BUT I THINK 2183 01:23:24,538 --> 01:23:25,906 TRULY LOOKING AT THE NUMBERS AND 2184 01:23:25,906 --> 01:23:31,411 JUST LOOKING AT THE ETHICS OF IT 2185 01:23:31,411 --> 01:23:35,749 THERE'S A STRONG ARGUMENT FOR 2186 01:23:35,749 --> 01:23:37,117 PREVENTING SEPSIS, THROUGH ALL 2187 01:23:37,117 --> 01:23:39,219 SORTS OF METHODS I AND OTHERS 2188 01:23:39,219 --> 01:23:43,791 HAVE ALREADY STARTED TO BRING UP 2189 01:23:43,791 --> 01:23:46,293 TODAY. 2190 01:23:46,293 --> 01:23:47,227 2191 01:23:47,227 --> 01:23:51,899 >> I THINK KRISTINA SET IT 2192 01:23:51,899 --> 01:23:54,735 RIGHT, IT'S ETHICAL, MORAL, 2193 01:23:54,735 --> 01:23:56,270 HEALTHCARE CORRECT, AN 2194 01:23:56,270 --> 01:23:56,603 IMPERATIVE. 2195 01:23:56,603 --> 01:24:02,943 WE RECOGNIZE THE THE COMPLEXITF 2196 01:24:02,943 --> 01:24:03,610 SEPSIS. 2197 01:24:03,610 --> 01:24:05,412 WE SHOULD BE PREVENTING. 2198 01:24:05,412 --> 01:24:06,647 KRISTINA PROPOSED WHERE YOU MILD 2199 01:24:06,647 --> 01:24:08,282 BE ABLE TO USE TECHNOLOGY AND 2200 01:24:08,282 --> 01:24:10,150 TOOLS TO IDENTIFY HIGHER RISK 2201 01:24:10,150 --> 01:24:11,785 PATIENTS AND DO SURVEILLANCE AND 2202 01:24:11,785 --> 01:24:13,120 OTHER MONITORING WOULD HELP THEM 2203 01:24:13,120 --> 01:24:15,155 TO KNOW WHEN THEY SHOULD BE 2204 01:24:15,155 --> 01:24:18,759 CONCERNED OR SEEK HEALTH CARE. 2205 01:24:18,759 --> 01:24:22,062 AND THERE ARE OTHER ASPECTS TOO, 2206 01:24:22,062 --> 01:24:24,698 WE THINK OF SEPSIS AS INFECTION 2207 01:24:24,698 --> 01:24:25,899 THAT CREATES DYSREGULATED IMMUNE 2208 01:24:25,899 --> 01:24:28,769 RESPONSE, LEADS TO ORGAN 2209 01:24:28,769 --> 01:24:30,771 DYSFUNCTION, PREVENTION OF ORGAN 2210 01:24:30,771 --> 01:24:31,972 DYSFUNCTION MIGHT BE ANOTHER 2211 01:24:31,972 --> 01:24:32,172 ONE. 2212 01:24:32,172 --> 01:24:33,807 IT MAY TRACK WITH COMORBIDITIES, 2213 01:24:33,807 --> 01:24:35,209 HOW THOSE ARE RELATED, HOW WE 2214 01:24:35,209 --> 01:24:36,910 MIGHT BE ABLE TO HELP BETTER 2215 01:24:36,910 --> 01:24:41,048 UNDERSTAND THAT BUT THAT'S A 2216 01:24:41,048 --> 01:24:42,583 PATHOPHYSIOLOGIC COMPONENTS AND 2217 01:24:42,583 --> 01:24:44,985 MORE CLINICAL COMPONENT, ALMOST 2218 01:24:44,985 --> 01:24:45,319 EPIDEMIOLOGIC. 2219 01:24:45,319 --> 01:24:48,822 THE LATTER PART, WE FIND IT 2220 01:24:48,822 --> 01:24:53,694 EASIEST TO IMPLEMENT STRATEGIES 2221 01:24:53,694 --> 01:24:55,729 IN THE HOSPITAL. 2222 01:24:55,729 --> 01:24:56,864 PATIENTS HAVE ENGAGED THE 2223 01:24:56,864 --> 01:24:57,431 HEALTHCARE SYSTEM BUT WE'VE 2224 01:24:57,431 --> 01:24:59,800 MISSED A LOT OF EARLIER 2225 01:24:59,800 --> 01:25:00,467 OPPORTUNITIES, THAT'S NOT 2226 01:25:00,467 --> 01:25:01,902 CORRECT, IT'S NOT THE BEST WAY 2227 01:25:01,902 --> 01:25:03,103 TO DO IT. 2228 01:25:03,103 --> 01:25:04,438 I'M NOT ARGUING THAT HEALTHCARE 2229 01:25:04,438 --> 01:25:08,141 IS THE SAME BECAUSE CLEARLY IT'S 2230 01:25:08,141 --> 01:25:08,508 NOT. 2231 01:25:08,508 --> 01:25:09,076 HOSPITALS ARE DIFFERENT, 2232 01:25:09,076 --> 01:25:10,777 PROVIDERS ARE DIFFERENT. 2233 01:25:10,777 --> 01:25:12,212 YOU CAN'T ARGUE SOMEONE 2234 01:25:12,212 --> 01:25:13,380 PRESENTING TO THE HEALTHCARE 2235 01:25:13,380 --> 01:25:14,581 SYSTEM IS THE SOLUTION. 2236 01:25:14,581 --> 01:25:16,183 SO THERE IS STILL THINGS -- 2237 01:25:16,183 --> 01:25:17,784 THERE ARE THINGS TO BE DONE IN 2238 01:25:17,784 --> 01:25:19,553 THAT REALM AS WELL, RIGHT, TO 2239 01:25:19,553 --> 01:25:20,754 BETTER DELIVER CARE FOR PEOPLE 2240 01:25:20,754 --> 01:25:23,257 WHO ARE CRITICALLY ILL OR HAVE 2241 01:25:23,257 --> 01:25:25,692 SEPSIS BUT I THINK SOMETIMES 2242 01:25:25,692 --> 01:25:26,560 WE'RE SIMPLISTIC THINKING THAT'S 2243 01:25:26,560 --> 01:25:29,062 THE PLACE TO START BECAUSE IT IS 2244 01:25:29,062 --> 01:25:30,731 PROBABLY EASIER BUT IT'S REALLY 2245 01:25:30,731 --> 01:25:32,165 MISSING PROBABLY THE BIGGER 2246 01:25:32,165 --> 01:25:33,467 PICTURE, WHERE WE HAVE THE 2247 01:25:33,467 --> 01:25:39,473 BETTER OPPORTUNITY TO PREVENT 2248 01:25:39,473 --> 01:25:39,806 SEPSIS. 2249 01:25:39,806 --> 01:25:43,210 >> I'M REMINDED OF HALLE 2250 01:25:43,210 --> 01:25:44,177 PRESCOTT'S WORK, PRE-HOSPITAL 2251 01:25:44,177 --> 01:25:48,048 TRAJECTORIES, HOW WE COULD 2252 01:25:48,048 --> 01:25:49,683 COMBINE THAT WITH 2253 01:25:49,683 --> 01:25:50,317 COMMUNITY-BASED PARTICIPATORY 2254 01:25:50,317 --> 01:25:52,953 RESEARCH, THINK ABOUT MODELS 2255 01:25:52,953 --> 01:25:55,589 COMMUNITIES THEMSELVES NEED TO 2256 01:25:55,589 --> 01:25:57,557 MOVE THAT CARE UPSTREAM. 2257 01:25:57,557 --> 01:25:58,892 >> YEAH. 2258 01:25:58,892 --> 01:26:00,961 >> ONE THING -- SORRY, GO AHEAD, 2259 01:26:00,961 --> 01:26:01,395 GREG. 2260 01:26:01,395 --> 01:26:03,797 >> QUICKLY, REMINDS ME OF WHAT 2261 01:26:03,797 --> 01:26:05,332 JOHN DONNELLY PUT IN, THERE'S 2262 01:26:05,332 --> 01:26:07,968 THE ACCESS TO CARE ELEMENT SO 2263 01:26:07,968 --> 01:26:09,603 THERE IS -- JOHN, YOU KNOW THIS 2264 01:26:09,603 --> 01:26:13,840 TOO, MANY OF YOU DO, THAT IN 2265 01:26:13,840 --> 01:26:15,275 MORE RURAL AREAS THERE ARE 2266 01:26:15,275 --> 01:26:15,976 CHALLENGES, RIGHT? 2267 01:26:15,976 --> 01:26:18,812 PARTICULARLY IN THE TIMELY 2268 01:26:18,812 --> 01:26:20,747 CONDITION LIKE THIS, PEOPLE 2269 01:26:20,747 --> 01:26:21,581 UNDERSTAND STROKE, CARDIAC 2270 01:26:21,581 --> 01:26:23,617 ARREST, MAYBE M.I. 2271 01:26:23,617 --> 01:26:24,484 THEY DON'T NECESSARILY 2272 01:26:24,484 --> 01:26:26,253 UNDERSTAND SEPSIS OR URGENCY OF 2273 01:26:26,253 --> 01:26:28,221 SEEKING CARE FOR PEOPLE THAT ARE 2274 01:26:28,221 --> 01:26:28,989 FURTHER AWAY FROM HEALTHCARE 2275 01:26:28,989 --> 01:26:30,324 SYSTEM THAT BECOMES A PROBLEM 2276 01:26:30,324 --> 01:26:34,795 FOR DELIVERING TIMELY CARE AS 2277 01:26:34,795 --> 01:26:35,762 WELL. 2278 01:26:35,762 --> 01:26:36,563 THERE'S AN EDUCATIONAL COMPONENT 2279 01:26:36,563 --> 01:26:38,632 THAT NEEDS TO HAPPEN AS WELL. 2280 01:26:38,632 --> 01:26:39,967 >> THE MESSAGING TO THE 2281 01:26:39,967 --> 01:26:42,769 COMMUNITY, THERE'S A LOT OF 2282 01:26:42,769 --> 01:26:44,571 POTENTIAL THERE, AND KRISTINA 2283 01:26:44,571 --> 01:26:46,940 MENTIONED WE TALK ABOUT THE LINK 2284 01:26:46,940 --> 01:26:48,342 BETWEEN COMORBIDITIES AND ORGAN 2285 01:26:48,342 --> 01:26:50,210 DYSFUNCTION AND OUTCOMES IN 2286 01:26:50,210 --> 01:26:52,079 SEPSIS BUT THERE'S ALSO THE 2287 01:26:52,079 --> 01:26:54,081 COMPONENTS OF HOW WE TREAT 2288 01:26:54,081 --> 01:26:56,516 MORBIDITY AND CONTROL OF THE 2289 01:26:56,516 --> 01:26:56,817 COMORBIDITY. 2290 01:26:56,817 --> 01:26:58,251 SO IF THERE'S AN OPPORTUNITY FOR 2291 01:26:58,251 --> 01:27:00,320 US TO HAVE MORE DATA REGARDING 2292 01:27:00,320 --> 01:27:03,523 THAT AND MESSAGING THE COMMUNITY 2293 01:27:03,523 --> 01:27:05,592 AND PATIENTS AND PROVIDERS, 2294 01:27:05,592 --> 01:27:09,629 THERE IS A BETTER OPPORTUNITIES 2295 01:27:09,629 --> 01:27:10,163 TO IMPACT PREVENTION. 2296 01:27:10,163 --> 01:27:11,064 >> YEAH, I AGREE. 2297 01:27:11,064 --> 01:27:13,333 I THINK I WOULD TAKE THAT ONE 2298 01:27:13,333 --> 01:27:14,101 STEP FORWARD. 2299 01:27:14,101 --> 01:27:17,404 EVEN THOUGH I FOCUS PRIMARILY IN 2300 01:27:17,404 --> 01:27:18,605 THINKING ABOUT INDIVIDUAL LEVEL 2301 01:27:18,605 --> 01:27:22,876 MEDICAL RISK FACTORS FOR SEPSIS, 2302 01:27:22,876 --> 01:27:24,311 PARTICULARLY CERTAIN 2303 01:27:24,311 --> 01:27:29,116 COMORBIDITIES, ESPECIALLY 2304 01:27:29,116 --> 01:27:31,752 MULTI-MORBIDITY AND GREG TOOK US 2305 01:27:31,752 --> 01:27:33,487 THROUGH RISKS, BIOLOGIC AND 2306 01:27:33,487 --> 01:27:34,688 SOCIAL, I THINK, YOU KNOW, WE 2307 01:27:34,688 --> 01:27:38,091 REALLY NEED TO BE THINKING MORE 2308 01:27:38,091 --> 01:27:40,327 ABOUT NOT ONLY INDIVIDUAL LEVEL 2309 01:27:40,327 --> 01:27:42,496 MEDICAL RISK BUT SOCIAL 2310 01:27:42,496 --> 01:27:43,363 DETERMINANTS OF HEALTH, 2311 01:27:43,363 --> 01:27:44,564 PARTICULARLY DETERMINANTS OF THE 2312 01:27:44,564 --> 01:27:46,366 COMMUNITY LEVEL AND SOCIETY 2313 01:27:46,366 --> 01:27:50,504 LEVEL, AND KIND OF THE DATA THAT 2314 01:27:50,504 --> 01:27:52,039 CHRIS IS PRESENTING, THINKING 2315 01:27:52,039 --> 01:27:55,075 ABOUT HOW CAN WE PREVENT SEPSIS, 2316 01:27:55,075 --> 01:27:57,177 NOT ONLY BY FINDING INDIVIDUAL 2317 01:27:57,177 --> 01:28:00,147 PATIENTS AT RISK AND TINKERING 2318 01:28:00,147 --> 01:28:02,082 WITH THEIR MEDICATIONS AND 2319 01:28:02,082 --> 01:28:03,650 MEDICAL MANAGEMENT TO REDUCE 2320 01:28:03,650 --> 01:28:04,618 THEIR RISK, THERE'S A LOT OF 2321 01:28:04,618 --> 01:28:06,920 THINGS WE CAN BE DOING AT THE 2322 01:28:06,920 --> 01:28:08,655 COMMUNITY LEVELS OR EVEN 2323 01:28:08,655 --> 01:28:10,190 SOCIETAL LEVELS TO BE THINKING 2324 01:28:10,190 --> 01:28:12,726 ABOUT HOW CAN WE PREVENT SEPSIS 2325 01:28:12,726 --> 01:28:13,894 AMONG WHOLE COMMUNITIES OF 2326 01:28:13,894 --> 01:28:15,962 PATIENTS WHO MIGHT BE AT RISK. 2327 01:28:15,962 --> 01:28:19,466 I'D LOVE TO HEAR DR. CHESLEY OR 2328 01:28:19,466 --> 01:28:21,201 DR. DONNELLY, THEY MAY HAVE 2329 01:28:21,201 --> 01:28:22,636 OTHER THOUGHTS, WHERE SHOULD WE 2330 01:28:22,636 --> 01:28:27,340 FOCUS BEYOND JUST THE 2331 01:28:27,340 --> 01:28:27,641 INDIVIDUAL? 2332 01:28:27,641 --> 01:28:30,277 >> I CAN JUMP IN. 2333 01:28:30,277 --> 01:28:34,047 YOU KNOW, I THINK ABOUT THIS IN 2334 01:28:34,047 --> 01:28:36,216 A FEW WAYS. 2335 01:28:36,216 --> 01:28:45,325 CERTAINLY THERE NEEDS TO BE MORE 2336 01:28:45,325 --> 01:28:46,726 UNDERSTANDING OF WHICH 2337 01:28:46,726 --> 01:28:48,261 STRUCTURAL DISADVANTAGE CONTEXTS 2338 01:28:48,261 --> 01:28:50,564 INFLUENCE SEPSIS RISK FACTORS, 2339 01:28:50,564 --> 01:28:51,865 PROBABLY ALSO THINGS THAT WERE 2340 01:28:51,865 --> 01:28:54,367 SORT OF MENTIONED BY DOCTORS 2341 01:28:54,367 --> 01:28:55,802 MARTIN AND RUDD, CAPTURING 2342 01:28:55,802 --> 01:28:57,571 PATIENTS THAT DON'T HAVE THAT 2343 01:28:57,571 --> 01:28:59,206 INTERSECTION WITH THE HEALTH 2344 01:28:59,206 --> 01:29:00,740 SYSTEM APPROPRIATELY, AND THAT 2345 01:29:00,740 --> 01:29:03,577 LEADS TO ADVERSE OUTCOMES. 2346 01:29:03,577 --> 01:29:05,245 SO IT'S CERTAINLY THAT NEEDS TO 2347 01:29:05,245 --> 01:29:09,249 BE AN AREA WHERE WE UNDERSTAND 2348 01:29:09,249 --> 01:29:11,785 MORE AS BOTH HEALTH CARE SYSTEM, 2349 01:29:11,785 --> 01:29:12,552 RESEARCHERS, HEALTH CARE 2350 01:29:12,552 --> 01:29:13,420 PROVIDERS. 2351 01:29:13,420 --> 01:29:15,288 THAT'S ONE. 2352 01:29:15,288 --> 01:29:19,993 BUT I HAVE THOUGHT ABOUT WHAT'S 2353 01:29:19,993 --> 01:29:22,395 ANALOGOUS IN OTHER FIELDS, AND 2354 01:29:22,395 --> 01:29:27,100 SO I REALLY THINK THE DEFINITION 2355 01:29:27,100 --> 01:29:29,102 OF SEPSIS ESPECIALLY AS EXISTS 2356 01:29:29,102 --> 01:29:31,371 NOW IS DIFFICULT TO WORK WITH AS 2357 01:29:31,371 --> 01:29:36,710 SOMEONE TRYING TO THINK ABOUT 2358 01:29:36,710 --> 01:29:39,346 DISEASE PREVENTION BECAUSE WHEN 2359 01:29:39,346 --> 01:29:45,152 YOU MAKE A A DEFINITION PREDICD 2360 01:29:45,152 --> 01:29:50,190 ON ORGAN FUNCTION, DIFFICULT TO 2361 01:29:50,190 --> 01:29:51,591 THINK ABOUT POPULATION AT 2362 01:29:51,591 --> 01:29:54,227 HIGHEST RISK, THERE'S 2363 01:29:54,227 --> 01:29:55,128 OPPORTUNITY THINKING ABOUT 2364 01:29:55,128 --> 01:29:58,932 STRUCTURAL DISADVANTAGE, HOW 2365 01:29:58,932 --> 01:30:01,768 THOSE RISK FACTORS COME TOGETHER 2366 01:30:01,768 --> 01:30:09,442 BECAUSE THAT INTERSECTION, I 2367 01:30:09,442 --> 01:30:11,945 I 2368 01:30:11,945 --> 01:30:13,380 ALLUDED IN THE CHAT, RISK 2369 01:30:13,380 --> 01:30:18,752 FACTORS CAN GET TO IDEAS OF 2370 01:30:18,752 --> 01:30:20,587 BIOLOGICAL PROFILES THAT PORTEND 2371 01:30:20,587 --> 01:30:21,788 THESE ADVERSE OUTCOMES THAT LEAD 2372 01:30:21,788 --> 01:30:24,958 TO DISPARITIES IN A WAY WE'RE 2373 01:30:24,958 --> 01:30:26,393 NOT THINKING ABOUT CURRENTLY AND 2374 01:30:26,393 --> 01:30:28,595 I'LL STOP WITH MY KIND OF LIKE 2375 01:30:28,595 --> 01:30:38,672 SOAP BOX HERE SAYING A TARGET 2376 01:30:38,672 --> 01:30:38,872 ED 2377 01:30:38,872 --> 01:30:39,673 BIOMARKER WOULD BE HELPFUL AS A 2378 01:30:39,673 --> 01:30:40,874 FIRST STEP. 2379 01:30:40,874 --> 01:30:49,950 I DON'T THINK WE'RE THERE YET, 2380 01:30:49,950 --> 01:30:54,120 AS A FIELD. 2381 01:30:54,120 --> 01:30:54,487 >> DEFINITELY. 2382 01:30:54,487 --> 01:30:56,723 THE COMMUNICATION WITH THE FIELD 2383 01:30:56,723 --> 01:30:57,857 AND WITH THE COMMUNITY HAS FELT 2384 01:30:57,857 --> 01:31:01,161 LIKE A REALLY BIG CHALLENGE, AND 2385 01:31:01,161 --> 01:31:03,296 KIND OF UNDERSTANDING, YOU KNOW, 2386 01:31:03,296 --> 01:31:05,799 HOW SOMETHING LIKE A FAIRLY 2387 01:31:05,799 --> 01:31:08,335 STRAIGHTFORWARD INFECTION COULD 2388 01:31:08,335 --> 01:31:10,637 END UP GOING TOWARDS SEPSIS. 2389 01:31:10,637 --> 01:31:14,674 SO IT FEELS LIKE THE SEPSIS 2390 01:31:14,674 --> 01:31:16,176 AWARENESS ORGANIZATIONS AND 2391 01:31:16,176 --> 01:31:17,978 LEVERAGING OTHER ASPECTS TO HELP 2392 01:31:17,978 --> 01:31:18,979 WITH THE COMMUNICATION PIECE IS 2393 01:31:18,979 --> 01:31:21,281 AN AREA THAT I DON'T PERSONALLY 2394 01:31:21,281 --> 01:31:22,215 HAVE EXPERIENCE OR EXPERTISE IN 2395 01:31:22,215 --> 01:31:25,185 BUT IT WOULD BE GREAT TO LEARN A 2396 01:31:25,185 --> 01:31:26,419 LITTLE BIT MORE ABOUT WHAT'S 2397 01:31:26,419 --> 01:31:32,092 BEEN EFFECTIVE THERE. 2398 01:31:32,092 --> 01:31:35,595 >> WE HAVE A QUESTION FROM THE 2399 01:31:35,595 --> 01:31:35,862 AUDIENCE. 2400 01:31:35,862 --> 01:31:39,266 >> YEAH, MAY I HAVE A QUESTION? 2401 01:31:39,266 --> 01:31:40,066 SO, YEAH -- 2402 01:31:40,066 --> 01:31:45,672 >> PLEASE STATE YOUR NAME. 2403 01:31:45,672 --> 01:31:48,275 >> YEAH, DANIEL LEE FROM TEXAS 2404 01:31:48,275 --> 01:31:49,276 A & M UNIVERSITY. 2405 01:31:49,276 --> 01:31:52,946 SO, GREAT SESSION. 2406 01:31:52,946 --> 01:31:54,281 AND GREAT TALKS. 2407 01:31:54,281 --> 01:31:55,849 MY QUESTION IS IN ADDITION TO 2408 01:31:55,849 --> 01:32:02,956 THE LIVING CONDITION, SUCH AS 2409 01:32:02,956 --> 01:32:05,759 POVERTY, GENETIC BACKGROUND SUCH 2410 01:32:05,759 --> 01:32:07,327 AS GENE EXPRESSION LEVELS, 2411 01:32:07,327 --> 01:32:12,699 DIFFERENCE IN IMMUNE CELL 2412 01:32:12,699 --> 01:32:13,566 FUNCTION, RACIAL DISPARITIES. 2413 01:32:13,566 --> 01:32:15,101 >> I'M HAPPY TO TAKE A FIRST 2414 01:32:15,101 --> 01:32:16,970 PASS ON THAT QUESTION. 2415 01:32:16,970 --> 01:32:20,040 SO, IT'S A GOOD QUESTION, IT'S 2416 01:32:20,040 --> 01:32:21,374 TALKING ABOUT BIOLOGICAL 2417 01:32:21,374 --> 01:32:23,276 DETERMINANTS FOR SEPSIS AND 2418 01:32:23,276 --> 01:32:23,576 DISPARITIES. 2419 01:32:23,576 --> 01:32:26,746 I THINK IT'S THE FIRST PLACE TO 2420 01:32:26,746 --> 01:32:30,984 START, RECOGNITION THERE ARE NO 2421 01:32:30,984 --> 01:32:32,952 GENETIC EPITOPES THAT SEPARATE 2422 01:32:32,952 --> 01:32:35,322 RACIAL GROUPS FROM EACH OTHER IN 2423 01:32:35,322 --> 01:32:39,993 A WAY THAT HAS BEEN VALIDATED 2424 01:32:39,993 --> 01:32:41,161 CONSISTENT AND POPULATION 2425 01:32:41,161 --> 01:32:43,363 ATTRIBUTABLE. 2426 01:32:43,363 --> 01:32:48,835 ESPECIALLY GIVEN THE AMOUNT OF 2427 01:32:48,835 --> 01:32:50,470 GENETIC ADMIXTURE BETWEEN RACES, 2428 01:32:50,470 --> 01:32:54,974 IT BECOMES DIFFICULT TO THINK 2429 01:32:54,974 --> 01:32:57,043 ABOUT HOW GENETIC DIFFERENCES 2430 01:32:57,043 --> 01:33:02,749 COULD REPRESENT TARGETABLE OR 2431 01:33:02,749 --> 01:33:10,490 RELIABLE MARKER FOR ADVERSE 2432 01:33:10,490 --> 01:33:11,891 SEPSIS OUTCOME IN CONTEXT OF 2433 01:33:11,891 --> 01:33:12,992 RACE. 2434 01:33:12,992 --> 01:33:14,861 THE COMMENT ABOUT BIOLOGICAL 2435 01:33:14,861 --> 01:33:15,662 IMPACT ON RACIAL DISPARITIES, I 2436 01:33:15,662 --> 01:33:17,630 THINK ONE THING THAT WE HAVE NOT 2437 01:33:17,630 --> 01:33:22,302 DONE AS GOOD A JOB MUCH AT 2438 01:33:22,302 --> 01:33:22,869 UNDERSTANDING BEYOND JUST 2439 01:33:22,869 --> 01:33:23,837 GENETICS, BIOLOGICAL PROFILES 2440 01:33:23,837 --> 01:33:28,541 THAT COULD BE ASSOCIATED WITH 2441 01:33:28,541 --> 01:33:32,612 RACIAL DIFFERENCES, AND THEN HOW 2442 01:33:32,612 --> 01:33:34,247 MUTABILITY OF PROFILES OVER TIME 2443 01:33:34,247 --> 01:33:35,281 CONTRIBUTES TO DIFFERENT 2444 01:33:35,281 --> 01:33:39,819 POPULATION RISK, BUT IN TERMS OF 2445 01:33:39,819 --> 01:33:42,288 DISTINCT, YOU KNOW, IDENTIFIED 2446 01:33:42,288 --> 01:33:44,891 GENETIC EPITOPES THAT SEPARATE, 2447 01:33:44,891 --> 01:33:46,326 YOU KNOW, DISEASE OUTCOME 2448 01:33:46,326 --> 01:33:50,029 DIFFERENCES BETWEEN RACES HAVE 2449 01:33:50,029 --> 01:33:52,465 YET TO BE STUDIED BECAUSE IT'S A 2450 01:33:52,465 --> 01:33:53,767 SIMPLE MATTER BEING VARIABLE 2451 01:33:53,767 --> 01:33:56,403 GROUPS ARE ABLE TO BE HAVE 2452 01:33:56,403 --> 01:33:59,672 GENETIC ADMIXTURE, AND THAT'S 2453 01:33:59,672 --> 01:34:01,741 WERE GENETICS BECOME HELPFUL. 2454 01:34:01,741 --> 01:34:05,245 >> ONE THING I'LL ADD, I TOTALLY 2455 01:34:05,245 --> 01:34:06,913 AGREE, DR. CHESLEY PUTTING 2456 01:34:06,913 --> 01:34:09,282 TOGETHER PIECES FROM DR. MARTIN 2457 01:34:09,282 --> 01:34:10,717 AND DR. RUDD'S TALKS, DR. MARTIN 2458 01:34:10,717 --> 01:34:13,686 SHOWED HOW AGE IS SUCH A HUGE 2459 01:34:13,686 --> 01:34:16,656 RISK FACTOR FOR SEPSIS INCIDENCE 2460 01:34:16,656 --> 01:34:18,725 AND MORTALITY, DR. RUDD, YOU 2461 01:34:18,725 --> 01:34:21,661 WERE TALKING ABOUT DIFFERENCE 2462 01:34:21,661 --> 01:34:23,430 BETWEEN BIOLOGICAL AND 2463 01:34:23,430 --> 01:34:24,297 CHRONOLOGICAL AGE WITH 2464 01:34:24,297 --> 01:34:27,700 EPIGENETIC STUDY YOU SHARED, 2465 01:34:27,700 --> 01:34:29,235 THAT THERE'S RACISM GETS UNDER 2466 01:34:29,235 --> 01:34:31,538 YOUR SKIN, POVERTY GETS UNDER 2467 01:34:31,538 --> 01:34:33,740 YOUR SKIN, LITERALLY, THE 2468 01:34:33,740 --> 01:34:35,475 CONCEPT OF EMBODIEDNESS THAT 2469 01:34:35,475 --> 01:34:37,110 HUMAN BEINGS EMBODY THEIR 2470 01:34:37,110 --> 01:34:40,079 EXPERIENCES, MEANING THAT THE 2471 01:34:40,079 --> 01:34:43,383 SOCIAL CONDITIONS THAT WE FACE 2472 01:34:43,383 --> 01:34:44,451 CAN GET PROGRAMMED 2473 01:34:44,451 --> 01:34:45,885 EPIGENETICALLY AND THEN CHANGED, 2474 01:34:45,885 --> 01:34:48,288 THE WAY WE AGE, SO THAT MAY BE 2475 01:34:48,288 --> 01:34:50,256 ONE POTENTIAL MECHANISM THAT MAY 2476 01:34:50,256 --> 01:34:51,791 ALSO EXPLAIN WHY BLACK PATIENTS 2477 01:34:51,791 --> 01:34:54,928 ARE SO MUCH YOUNGER ON AVERAGE 2478 01:34:54,928 --> 01:34:57,597 WHEN THEY BECOME CLINICALLY ILL 2479 01:34:57,597 --> 01:34:59,332 AND THERE BY CHRONOLOGICAL AGE 2480 01:34:59,332 --> 01:35:00,800 IS YOUNG BUT BIOLOGICAL AGE MAY 2481 01:35:00,800 --> 01:35:03,837 BE GREATER BECAUSE OF THE SOCIAL 2482 01:35:03,837 --> 01:35:06,339 DISADVANTAGES BEING FACED. 2483 01:35:06,339 --> 01:35:08,942 >> I THINK THAT'S ONE MORE 2484 01:35:08,942 --> 01:35:10,376 ELEMENT LIKE CHRIS WAS SAYING 2485 01:35:10,376 --> 01:35:12,111 THERE'S THE ELEMENT OF 2486 01:35:12,111 --> 01:35:13,012 BIOLOGICAL AND STRUCTURAL 2487 01:35:13,012 --> 01:35:15,849 ELEMENTS, BUT THAT'S ANOTHER 2488 01:35:15,849 --> 01:35:22,288 ONE, GOOD TO BETTER UNDERSTAND 2489 01:35:22,288 --> 01:35:23,723 CHRONOLOGIC AGE. 2490 01:35:23,723 --> 01:35:25,258 I WOULD ADD, CHRIS SAID NICELY, 2491 01:35:25,258 --> 01:35:26,626 MUCH OF THE DISPARITY WORK IN 2492 01:35:26,626 --> 01:35:28,328 SEPSIS IS BASED IN THE U.S. 2493 01:35:28,328 --> 01:35:36,002 WHAT CHRIS SAID IS ABSOLUTELY 2494 01:35:36,002 --> 01:35:36,736 RIGHT, LIKE RACE AND GENETICS DO 2495 01:35:36,736 --> 01:35:41,241 NOT TRACK IN THE U.S., RACE AND 2496 01:35:41,241 --> 01:35:42,208 POLYMORPHISMS. 2497 01:35:42,208 --> 01:35:43,877 THERE ARE GENDER DIFFERENCES 2498 01:35:43,877 --> 01:35:45,812 ELSE IN THE WORLD, OTHER 2499 01:35:45,812 --> 01:35:50,783 DISPARITIES, BUT IF THERE IS A 2500 01:35:50,783 --> 01:35:52,952 GENETIC FACTOR, FOR INSTANCE 2501 01:35:52,952 --> 01:35:54,954 DISPARITIES BASED ON RACE OR 2502 01:35:54,954 --> 01:35:57,123 GENDER IN NEONATES, WHERE MAYBE 2503 01:35:57,123 --> 01:35:59,559 OTHER THINGS, RIGHT, YOU'RE IN 2504 01:35:59,559 --> 01:36:01,294 THE HOSPITAL, YOU'RE NEWBORN, 2505 01:36:01,294 --> 01:36:03,062 STILL THAT DOESN'T MITIGATE SOME 2506 01:36:03,062 --> 01:36:04,597 SOCIAL DETERMINANTS SO WE 2507 01:36:04,597 --> 01:36:05,999 REALIZE THERE'S OTHER FACTORS. 2508 01:36:05,999 --> 01:36:07,233 SOMETIMES PEOPLE POINTED TO THAT 2509 01:36:07,233 --> 01:36:09,969 AS ONE WAY OF SAYING WELL, MAYBE 2510 01:36:09,969 --> 01:36:10,970 THERE'S SOMETHING MORE 2511 01:36:10,970 --> 01:36:11,371 BIOLOGICAL. 2512 01:36:11,371 --> 01:36:12,906 CHRIS IS ABSOLUTELY RIGHT. 2513 01:36:12,906 --> 01:36:13,806 THERE'S NO GENETIC FACTOR THAT'S 2514 01:36:13,806 --> 01:36:15,775 GOING TO TRACK AND CERTAINLY 2515 01:36:15,775 --> 01:36:17,310 IT'S OUTWEIGHED BY OTHER THINGS 2516 01:36:17,310 --> 01:36:24,517 WE SEE, VASTLY LARGER COMPONENTS 2517 01:36:24,517 --> 01:36:25,051 OF DISPARITIES. 2518 01:36:25,051 --> 01:36:26,252 >> DR. AGRIWAL, YOU HAVE A 2519 01:36:26,252 --> 01:36:26,786 QUESTION? 2520 01:36:26,786 --> 01:36:28,922 >> I WANT TO CIRCLE BACK ON THE 2521 01:36:28,922 --> 01:36:35,361 DEFINITION OF SEPSIS THAT TOOK 2522 01:36:35,361 --> 01:36:36,763 US -- ORGAN FAILURE OR THE 2523 01:36:36,763 --> 01:36:43,436 INFECTION OR IS IT BIOMARKER, I 2524 01:36:43,436 --> 01:36:46,839 WAS WONDERING WHAT'S THE 2525 01:36:46,839 --> 01:36:49,242 STANDARD OF CARE OR DIAGNOSTIC 2526 01:36:49,242 --> 01:36:50,343 PROCEDURE TO IDENTIFY THAT THE 2527 01:36:50,343 --> 01:36:52,979 PATIENT IS GOING INTO SEPSIS AND 2528 01:36:52,979 --> 01:36:55,615 IS IT THE BIOMARKER DISCOVERY OR 2529 01:36:55,615 --> 01:36:57,650 IS IT IMMUNE RESPONSE OF 2530 01:36:57,650 --> 01:37:00,653 NEUTROPHILS, HOW IS IT DONE AND 2531 01:37:00,653 --> 01:37:06,893 HOW SOON IS IT DONE AFTER WHICH 2532 01:37:06,893 --> 01:37:11,297 THE ANTIMICROBIAL REGIMEN CAN BE 2533 01:37:11,297 --> 01:37:11,631 ADMINISTERED? 2534 01:37:11,631 --> 01:37:13,166 AND HOW EFFECTIVE IT IS, IN THE 2535 01:37:13,166 --> 01:37:17,236 CURRENT STATE OF THE ART? 2536 01:37:17,236 --> 01:37:19,072 >> I'LL MAYBE TACKLE THAT FIRST. 2537 01:37:19,072 --> 01:37:20,807 I MIGHT EVEN THINK ABOUT WHAT 2538 01:37:20,807 --> 01:37:22,575 JOHN WAS DESCRIBING FOR 2539 01:37:22,575 --> 01:37:23,576 IMPLEMENTATION SCIENCE, HOW YOU 2540 01:37:23,576 --> 01:37:25,678 THINK ABOUT THAT FROM A PROCESS 2541 01:37:25,678 --> 01:37:25,979 PERSPECTIVE. 2542 01:37:25,979 --> 01:37:28,047 I THINK WE ALL HAVE EXPERIENCE 2543 01:37:28,047 --> 01:37:28,948 WIT. 2544 01:37:28,948 --> 01:37:32,752 WE ALL REALIZE THERE'S 2545 01:37:32,752 --> 01:37:34,087 INITIATIVES IN PLACE. 2546 01:37:34,087 --> 01:37:35,722 I DON'T THINK WE'RE CONSISTENT 2547 01:37:35,722 --> 01:37:38,891 ABOUT IT IN MANY WAYS, I THINK 2548 01:37:38,891 --> 01:37:40,460 SURVEY LINK FOR INFECTION MAY BE 2549 01:37:40,460 --> 01:37:44,297 ONE OF THE KEYS, WHY KRISTINA 2550 01:37:44,297 --> 01:37:45,698 WAS USING TECHNOLOGIES TO 2551 01:37:45,698 --> 01:37:47,700 IDENTIFY HIGH RISK POPULATIONS 2552 01:37:47,700 --> 01:37:49,769 WHICH ARE PROBABLY LOOKING FOR 2553 01:37:49,769 --> 01:37:54,374 INFECTION AMONG PEOPLE WHO ARE 2554 01:37:54,374 --> 01:37:57,543 AT HIGHER RISK OF DEVELOPING 2555 01:37:57,543 --> 01:37:58,645 SEPSIS, IDENTIFYING PEOPLE WITH 2556 01:37:58,645 --> 01:37:59,512 ORGAN DYSFUNCTION IS TOO FAR 2557 01:37:59,512 --> 01:38:02,148 DOWN THE ROAD TO HAVE THE 2558 01:38:02,148 --> 01:38:04,550 OPPORTUNITIES FOR PREVENTION. 2559 01:38:04,550 --> 01:38:05,985 IN MY MIND, AND THIS GETS BACK 2560 01:38:05,985 --> 01:38:10,990 TO UP IS SIS -- SEPSIS 2561 01:38:10,990 --> 01:38:12,558 DEFINITION WHICH I'LL TACKLE, I 2562 01:38:12,558 --> 01:38:14,861 WAS A CO-AUTHOR, WE STEPPED AWAY 2563 01:38:14,861 --> 01:38:19,799 FROM A COUPLE THINGS. 2564 01:38:19,799 --> 01:38:22,435 WE DO REALIZE SIRS WAS A 2565 01:38:22,435 --> 01:38:23,503 SURVEILLANCE TOOL, LARGELY USED 2566 01:38:23,503 --> 01:38:25,271 TO TRY AND IDENTIFY PEOPLE 2567 01:38:25,271 --> 01:38:26,639 HAVING THAT ABERRANT RESPONSE. 2568 01:38:26,639 --> 01:38:28,641 IT'S STILL DOWNSTREAM OF THE 2569 01:38:28,641 --> 01:38:29,308 INFECTION AND POTENTIALLY 2570 01:38:29,308 --> 01:38:31,277 DOWNSTREAM OF WHAT WE MIGHT BE 2571 01:38:31,277 --> 01:38:34,113 ABLE TO IDENTIFY PEOPLE AT RISK 2572 01:38:34,113 --> 01:38:35,214 OF SEPSIS AND ORGAN DYSFUNCTION. 2573 01:38:35,214 --> 01:38:40,453 AND THE OTHER PART IS THAT ORGAN 2574 01:38:40,453 --> 01:38:41,454 DYSFUNCTION COMPONENT IS 2575 01:38:41,454 --> 01:38:41,721 IMPERFECT. 2576 01:38:41,721 --> 01:38:44,190 I WAS ONE OF THE DISSENTERS IN 2577 01:38:44,190 --> 01:38:45,591 THAT GROUP THAT FELT LIKE 2578 01:38:45,591 --> 01:38:47,460 MAINTAINING AN ELEMENT OF MOVING 2579 01:38:47,460 --> 01:38:49,996 FROM UPSTREAM TO FURTHER 2580 01:38:49,996 --> 01:38:52,932 DOWNSTREAM WAS IMPORTANT, FOR 2581 01:38:52,932 --> 01:38:55,234 EPIDEMIOLOGIC AND CLINICAL 2582 01:38:55,234 --> 01:38:58,304 PURPOSES, BUT CONCEPTUALLY THE 2583 01:38:58,304 --> 01:38:59,839 CONCEPT STILL WORKS. 2584 01:38:59,839 --> 01:39:01,607 THE PURPOSE HERE IS TO SAY, YOU 2585 01:39:01,607 --> 01:39:03,476 KNOW, IF SEPSIS IS DEFINED BY 2586 01:39:03,476 --> 01:39:04,977 ORGAN DYSFUNCTION WE NEED TO BE 2587 01:39:04,977 --> 01:39:06,846 UPSTREAM OF THAT, WHETHER YOU 2588 01:39:06,846 --> 01:39:09,916 CALL THAT INFECTION, WITH 2589 01:39:09,916 --> 01:39:11,951 SEPSIS, EVERYTHING UPSTREAM IS 2590 01:39:11,951 --> 01:39:12,618 INFECTION, THAT SURVEILLANCE 2591 01:39:12,618 --> 01:39:14,387 ELEMENT STILL NEEDS TO BE IN 2592 01:39:14,387 --> 01:39:16,355 PLACE WHETHER YOU'RE SURVEILLING 2593 01:39:16,355 --> 01:39:19,092 USING BIOMARKERS FOR ABERRANT 2594 01:39:19,092 --> 01:39:22,261 RESPONSE TO THE INFECTION OR 2595 01:39:22,261 --> 01:39:24,864 SURVEILLING FOR THE INFECTION OR 2596 01:39:24,864 --> 01:39:26,966 USING CLINICAL RISK FACTORS, 2597 01:39:26,966 --> 01:39:28,601 WHAT THE IMPLEMENTATION SCIENCE 2598 01:39:28,601 --> 01:39:30,336 PIECE COMES IN. 2599 01:39:30,336 --> 01:39:32,538 I'D LOVE TO HEAR OTHERS, BECAUSE 2600 01:39:32,538 --> 01:39:38,344 EVERYONE ELSE WORKS ON THIS TOO. 2601 01:39:38,344 --> 01:39:40,113 >> SUPER QUICKLY, I FULLY AGREE 2602 01:39:40,113 --> 01:39:42,115 AND I THINK ONE CHALLENGE KIND 2603 01:39:42,115 --> 01:39:44,951 OF WITH THAT, THE UPSTREAM 2604 01:39:44,951 --> 01:39:46,686 PIECE, HAS BEEN WORKING IN 2605 01:39:46,686 --> 01:39:48,321 SYSTEMS THAT AREN'T NECESSARILY 2606 01:39:48,321 --> 01:39:51,057 FULLY INTEGRATED SO I THINK 2607 01:39:51,057 --> 01:39:53,793 FULLY INTEGRATED WE'LL CALL IT 2608 01:39:53,793 --> 01:39:55,428 PRAGMATIC QUALITY IMPROVEMENT 2609 01:39:55,428 --> 01:39:57,530 WORK COULD BENEFIT FROM THINKING 2610 01:39:57,530 --> 01:40:00,133 THROUGH HOW WE CONSIDER SEPSIS 2611 01:40:00,133 --> 01:40:03,202 RISK, AND WHETHER THERE'S A WAY 2612 01:40:03,202 --> 01:40:05,505 TO INCORPORATE SOME MORE 2613 01:40:05,505 --> 01:40:06,272 ADVANCED STATISTICAL TECHNIQUES 2614 01:40:06,272 --> 01:40:08,975 OR AT LEAST EVEN LIKE A MORE 2615 01:40:08,975 --> 01:40:10,877 SIMPLISTIC RISK SCORE, I THINK 2616 01:40:10,877 --> 01:40:13,713 THAT PIECE HAS NOT BEEN FULLY 2617 01:40:13,713 --> 01:40:15,047 DEVELOPED FOR TOTALLY 2618 01:40:15,047 --> 01:40:15,782 UNDERSTANDABLE REASONS THAT 2619 01:40:15,782 --> 01:40:18,851 WOULD BE VERY DIFFICULT TO 2620 01:40:18,851 --> 01:40:25,525 IMPLEMENT. 2621 01:40:25,525 --> 01:40:26,959 >> I HAVE A QUESTION. 2622 01:40:26,959 --> 01:40:30,129 REGARDING WHAT CHRIS WAS 2623 01:40:30,129 --> 01:40:31,998 MENTIONING, SO WHAT I UNDERSTAND 2624 01:40:31,998 --> 01:40:35,735 IS THAT THERE'S NOT MUCH STRONG 2625 01:40:35,735 --> 01:40:39,038 EVIDENCE TO SUPPORT GENETIC 2626 01:40:39,038 --> 01:40:39,839 FACTORS ASSOCIATED WITH 2627 01:40:39,839 --> 01:40:42,175 SUSCEPTIBILITY ESPECIALLY IN 2628 01:40:42,175 --> 01:40:42,642 AFRICAN AMERICANS. 2629 01:40:42,642 --> 01:40:44,610 IS IT -- DO YOU THINK IT HAS 2630 01:40:44,610 --> 01:40:48,214 MORE TO DO WITH THERE ARE NOT 2631 01:40:48,214 --> 01:40:49,682 STRONG GENOMIC DATABASES FOR 2632 01:40:49,682 --> 01:40:51,584 THIS POPULATION GROUP BECAUSE 2633 01:40:51,584 --> 01:40:56,088 MOST DATABASES ARE PRIMARILY 2634 01:40:56,088 --> 01:40:57,957 CAUCASIANS? 2635 01:40:57,957 --> 01:41:01,661 BECAUSE THERE ARE SOME STUDIES, 2636 01:41:01,661 --> 01:41:03,329 MAYBE VETERANS AFFAIRS, I 2637 01:41:03,329 --> 01:41:04,864 HAVEN'T SEEN MUCH STRONG GENOMIC 2638 01:41:04,864 --> 01:41:06,065 STUDIES DONE IN THESE PATIENTS, 2639 01:41:06,065 --> 01:41:08,768 SO DO YOU THINK THAT COULD BE A 2640 01:41:08,768 --> 01:41:09,001 FACTOR? 2641 01:41:09,001 --> 01:41:11,103 BECAUSE WE DON'T SEE ANYTHING 2642 01:41:11,103 --> 01:41:12,505 BECAUSE DATABASE DOESN'T EXIST? 2643 01:41:12,505 --> 01:41:14,373 >> YEAH, I THINK MULTIPLE 2644 01:41:14,373 --> 01:41:14,607 FACTORS. 2645 01:41:14,607 --> 01:41:18,411 I THINK ONE OF THEM HAS TO DO 2646 01:41:18,411 --> 01:41:19,846 WITH REPRESENTATION AND GENETIC 2647 01:41:19,846 --> 01:41:20,813 STUDIES CERTAINLY. 2648 01:41:20,813 --> 01:41:23,883 ALSO IT BECOMES CHALLENGING 2649 01:41:23,883 --> 01:41:28,354 MOVING FROM LIKE A STUDY IN 2650 01:41:28,354 --> 01:41:30,256 POPULATION, LIKE A NATIONAL 2651 01:41:30,256 --> 01:41:34,827 SCALE, EVEN MORE REGIONAL SCALE, 2652 01:41:34,827 --> 01:41:36,128 ENSURING THERE'S ENOUGH 2653 01:41:36,128 --> 01:41:36,762 DIVERSITY IN RECRUITING 2654 01:41:36,762 --> 01:41:38,531 POPULATIONS IS ONE THING. 2655 01:41:38,531 --> 01:41:42,501 BUT FOR ME, AGAIN I'M NOT A 2656 01:41:42,501 --> 01:41:44,904 GENETICS RESEARCH, I'M A HEALTH 2657 01:41:44,904 --> 01:41:48,374 THE QUESTION RESEARCHER, THE 2658 01:41:48,374 --> 01:41:50,910 IDEA THAT GENETICS AS A 2659 01:41:50,910 --> 01:41:51,510 BIOLOGICAL DIFFERENCE BETWEEN 2660 01:41:51,510 --> 01:41:53,012 RACES FALLS FLAT ON ITS HEAD 2661 01:41:53,012 --> 01:41:55,414 WHEN YOU ACKNOWLEDGE THAT RACIAL 2662 01:41:55,414 --> 01:41:58,818 GROUPS ARE ABLE TO HAVE -- TO 2663 01:41:58,818 --> 01:42:02,021 PROCREATE AND HAVE GENETICS AS 2664 01:42:02,021 --> 01:42:04,190 ANY KINDS OF, YOU KNOW, 2665 01:42:04,190 --> 01:42:07,326 COMBINATION SO IT'S REALLY A 2666 01:42:07,326 --> 01:42:07,593 SNAPSHOT. 2667 01:42:07,593 --> 01:42:08,995 LIKE EVERY GENETIC STUDY FROM 2668 01:42:08,995 --> 01:42:10,630 THAT PERSPECTIVE BECOMES A 2669 01:42:10,630 --> 01:42:13,699 SNAPSHOT IN TIME AND GIVEN TIME, 2670 01:42:13,699 --> 01:42:15,434 YOU KNOW, THESE POPULATION 2671 01:42:15,434 --> 01:42:17,169 DIFFERENCES THERE'S NOTHING 2672 01:42:17,169 --> 01:42:22,541 THAT, YOU KNOW, WOULD PREVENT 2673 01:42:22,541 --> 01:42:23,709 SOMEONE TO IDENTIFY AS ONE OR 2674 01:42:23,709 --> 01:42:26,612 OTHER RACE, SO SOME OF THIS -- 2675 01:42:26,612 --> 01:42:30,416 THIS IS THE STUFF OF THE SOCIAL 2676 01:42:30,416 --> 01:42:31,951 CONTEXT, SOCIAL DEFINITION OF 2677 01:42:31,951 --> 01:42:35,688 RACE AS A SOCIAL CONSTRUCT, 2678 01:42:35,688 --> 01:42:36,322 RATHER THAN BIOLOGICAL 2679 01:42:36,322 --> 01:42:36,589 CONSTRUCT. 2680 01:42:36,589 --> 01:42:39,191 AND SO I THINK IF WE THINK ABOUT 2681 01:42:39,191 --> 01:42:42,461 WHAT IS MOST USEFUL BANG FOR 2682 01:42:42,461 --> 01:42:43,329 BUCK WITH LIKE EITHER 2683 01:42:43,329 --> 01:42:46,065 INTERVENTION OR FOR LIKE THE 2684 01:42:46,065 --> 01:42:48,401 CONTEXT OF DESIGNING A STUDY, 2685 01:42:48,401 --> 01:42:51,604 FOCUSING PURELY ON THE GENETIC 2686 01:42:51,604 --> 01:42:58,044 PIECE OF SEPSIS RISK FACTOR AND 2687 01:42:58,044 --> 01:42:59,679 RACIAL DISPARITY SEEMS -- VERY 2688 01:42:59,679 --> 01:43:00,947 ALSO PROBABILITY THAT WOULD BE 2689 01:43:00,947 --> 01:43:03,849 EFFICIENT USE OF STUDY TIME, AS 2690 01:43:03,849 --> 01:43:08,955 A RESEARCHER THAT'S HOW I THINK 2691 01:43:08,955 --> 01:43:12,491 ABOUT IT. 2692 01:43:12,491 --> 01:43:14,360 ON SMALLER TIME SCALES, IT 2693 01:43:14,360 --> 01:43:17,763 SHOULD BE STUDIED, WHAT IT MEANS 2694 01:43:17,763 --> 01:43:22,001 TO BE GENERALIZABLE BUT IF I 2695 01:43:22,001 --> 01:43:27,940 DON'TS DON'T HAVE IT, MY 2696 01:43:27,940 --> 01:43:28,908 GRANDPARENTS DON'T HAVE THAT, 2697 01:43:28,908 --> 01:43:31,210 THEY ARE STILL AT RISK, FROM A 2698 01:43:31,210 --> 01:43:33,279 PRACTICAL PERSPECTIVE AND 2699 01:43:33,279 --> 01:43:36,782 RESEARCH AND KNOWN BIOLOGIC 2700 01:43:36,782 --> 01:43:40,820 CONSTRUCT, THAT'S KINDS OF 2701 01:43:40,820 --> 01:43:42,588 MATCHED TOGETHER. 2702 01:43:42,588 --> 01:43:49,862 >> I TOTALLY AGREE WITH WHAT DR. 2703 01:43:49,862 --> 01:43:52,665 CHESLEY SAID. 2704 01:43:52,665 --> 01:44:00,239 IT'S BEEN SHOWN INDIVIDUALS WITH 2705 01:44:00,239 --> 01:44:00,840 AFRICAN BACKGROUND HAVE MORE 2706 01:44:00,840 --> 01:44:02,441 GENETIC DIVERSITY. 2707 01:44:02,441 --> 01:44:09,648 A PERSON OF EUROPEAN ANCESTRY, 2708 01:44:09,648 --> 01:44:12,251 MORE SIMILAR THAN TWO SPECIES OF 2709 01:44:12,251 --> 01:44:12,952 AFRICAN ANCESTRY. 2710 01:44:12,952 --> 01:44:16,022 THERE'S BEEN MORE TIME ON THE 2711 01:44:16,022 --> 01:44:17,323 AFRICAN CONTINENT FOR GENETIC 2712 01:44:17,323 --> 01:44:17,890 DIVERSITY TO DEVELOP BECAUSE 2713 01:44:17,890 --> 01:44:21,027 THAT WAS SORT OF THE 2714 01:44:21,027 --> 01:44:22,228 ORIGINATION, AND THE SPECIES -- 2715 01:44:22,228 --> 01:44:23,763 THERE'S MORE GENETIC DIVERSITY 2716 01:44:23,763 --> 01:44:25,197 AMONG PEOPLE WHO WE IDENTIFY AS 2717 01:44:25,197 --> 01:44:26,499 BLACK IN THE UNITED STATES AND 2718 01:44:26,499 --> 01:44:30,336 SO IT WOULD NOT BE POSSIBLE FOR 2719 01:44:30,336 --> 01:44:32,838 THERE TO BE A SINGLE AGAINST 2720 01:44:32,838 --> 01:44:34,940 ROOT CAUSE OF THIS HIGHER 2721 01:44:34,940 --> 01:44:36,342 INCIDENCE OF SEPSIS IN THAT 2722 01:44:36,342 --> 01:44:39,178 GROUP. 2723 01:44:39,178 --> 01:44:43,783 DR. LEE WAS NEXT. 2724 01:44:43,783 --> 01:44:45,985 >> THANK YOU SO MUCH. 2725 01:44:45,985 --> 01:44:48,054 REALLY SOME WONDERFUL TALKS. 2726 01:44:48,054 --> 01:44:51,891 WHAT STRUCK ME FROM WHAT YOU ALL 2727 01:44:51,891 --> 01:44:54,193 DESCRIBED TOGETHER WAS THE 2728 01:44:54,193 --> 01:44:57,163 CHALLENGE OF WHO IS SPEAKING ON 2729 01:44:57,163 --> 01:45:00,399 THIS TOPIC. 2730 01:45:00,399 --> 01:45:01,967 LIKE EVERYONE HERE, LARGELY 2731 01:45:01,967 --> 01:45:02,601 PULMONARY AND CRITICAL CARE, 2732 01:45:02,601 --> 01:45:03,936 RESEARCH IN THE DOMAIN OF 2733 01:45:03,936 --> 01:45:05,237 HOSPITAL BASED OR SEVERE 2734 01:45:05,237 --> 01:45:06,906 INFECTION, BUT MANY OF THE 2735 01:45:06,906 --> 01:45:11,377 POINTS RAISED REALLY HAVE TO DO 2736 01:45:11,377 --> 01:45:15,214 WITH THE PRECURSORS, SYNDEMIC, 2737 01:45:15,214 --> 01:45:16,382 MULTI-MORBIDITY, GEOGRAPHIC OR 2738 01:45:16,382 --> 01:45:17,917 SEGREGATION, ALL THOSE OTHER 2739 01:45:17,917 --> 01:45:18,150 FACTORS. 2740 01:45:18,150 --> 01:45:20,786 I WONDER IF YOU HAVE THOUGHTS 2741 01:45:20,786 --> 01:45:22,655 WHO WE NEED TO BRING INTO THIS 2742 01:45:22,655 --> 01:45:25,591 CONVERSATION, HOW DO WE DO SO, 2743 01:45:25,591 --> 01:45:29,228 SO THAT WE CAN MAKE SURE WE 2744 01:45:29,228 --> 01:45:31,831 HAVE, YOU KNOW, REALLY SMART AND 2745 01:45:31,831 --> 01:45:35,134 TALENTED AND INNOVATIVE PEOPLE 2746 01:45:35,134 --> 01:45:36,368 WHO ACTUALLY HAVE THE LEVER AND 2747 01:45:36,368 --> 01:45:39,939 CAPE 2748 01:45:39,939 --> 01:45:42,575 CAPABILITY TO DO THAT WORK AND 2749 01:45:42,575 --> 01:45:44,643 IMPLEMENTATION OR INTERVENTION 2750 01:45:44,643 --> 01:45:48,347 ULTIMATELY. 2751 01:45:48,347 --> 01:45:48,914 >> TERRIFIC POINT. 2752 01:45:48,914 --> 01:45:51,517 THANK YOU FOR MAKING IT. 2753 01:45:51,517 --> 01:45:53,385 CLEARLY I'LL SAY SOMETHING THAT 2754 01:45:53,385 --> 01:45:55,888 EVERYONE WILL CONSIDER TO BE 2755 01:45:55,888 --> 01:45:59,425 OBVIOUS BUT IT NEEDS TO INVOLVE 2756 01:45:59,425 --> 01:46:00,960 DIVERSE GROUP OF PROFESSIONALS, 2757 01:46:00,960 --> 01:46:02,495 BUT I HAS TO ENGAGE HEALTH 2758 01:46:02,495 --> 01:46:03,462 SYSTEMS AND COMMUNITIES BECAUSE 2759 01:46:03,462 --> 01:46:07,500 IT'S ALL OF THOSE PIECES 2760 01:46:07,500 --> 01:46:08,701 TOGETHER AND IF I SAID HOW MIGHT 2761 01:46:08,701 --> 01:46:11,237 YOU DO THIS I WOULD THINK YOU 2762 01:46:11,237 --> 01:46:12,338 MIGHT START INTEGRATED HEALTH 2763 01:46:12,338 --> 01:46:18,878 SYSTEMS LIKE THE V.A. OR KAISER 2764 01:46:18,878 --> 01:46:20,513 WHERE SYSTEMS ARE INTEGRATED, 2765 01:46:20,513 --> 01:46:21,947 PATIENT ENCOUNTERS ARE CAPTURED, 2766 01:46:21,947 --> 01:46:23,249 PARTICULARLY IF ENGAGED IN A 2767 01:46:23,249 --> 01:46:25,351 COMMUNITY WITH A BETTER WAY TO 2768 01:46:25,351 --> 01:46:27,086 ROLL OUT AND TEST INTERVENTIONS 2769 01:46:27,086 --> 01:46:29,188 BUT THAT WOULD BE ONE WAY TO 2770 01:46:29,188 --> 01:46:31,257 BETTER UNDERSTAND A LOT OF 2771 01:46:31,257 --> 01:46:32,791 FACTORS WE'RE TALKING ABOUT, HOW 2772 01:46:32,791 --> 01:46:34,860 TO PULL THEM TOGETHER, WHAT 2773 01:46:34,860 --> 01:46:36,295 INTERVENTIONS ARE MOST 2774 01:46:36,295 --> 01:46:39,131 EFFECTIVE, BUT IN MY MIND IT'S A 2775 01:46:39,131 --> 01:46:39,698 HUGE OPPORTUNITY. 2776 01:46:39,698 --> 01:46:41,200 YOU CAN START IN DIFFERENT 2777 01:46:41,200 --> 01:46:42,768 PLACES BUT I THINK MAYBE THAT'S 2778 01:46:42,768 --> 01:46:46,338 THE EASIEST PRAISE -- PLACE TO 2779 01:46:46,338 --> 01:46:47,907 START BUT IT HAS TO PULL 2780 01:46:47,907 --> 01:46:54,580 TOGETHER STAKEHOLDERS TO MAKE IT 2781 01:46:54,580 --> 01:46:56,148 WORK. 2782 01:46:56,148 --> 01:47:02,121 >> I WILL PLUG SOCIOLOGISTS HERE 2783 01:47:02,121 --> 01:47:06,725 BECAUSE THEY HAVE A MORE ROBUST 2784 01:47:06,725 --> 01:47:09,228 UNDERSTANDING HOW TO 2785 01:47:09,228 --> 01:47:10,763 OPERATIONALIZE DISCRETE 2786 01:47:10,763 --> 01:47:11,697 STRUCTURAL DISADVANTAGE AND 2787 01:47:11,697 --> 01:47:14,266 DETERMINANTS THAT I THINK HAS 2788 01:47:14,266 --> 01:47:20,105 NOT BEEN EASILY OR MORE WIDELY 2789 01:47:20,105 --> 01:47:22,274 ADAPTED IN MANY HEALTHCARE 2790 01:47:22,274 --> 01:47:24,310 SITUATIONS SO A LOT OF WORK I 2791 01:47:24,310 --> 01:47:29,148 DO, IT IS TRYING TO LEARN ABOUT 2792 01:47:29,148 --> 01:47:32,318 HOW DIFFERENT STRUCTURAL 2793 01:47:32,318 --> 01:47:32,952 DETERMINANTS HAVE BEEN 2794 01:47:32,952 --> 01:47:35,254 OPERATIONALIZED IN THE FIELDS 2795 01:47:35,254 --> 01:47:36,589 SUCH AS EDUCATION, ECONOMICS 2796 01:47:36,589 --> 01:47:38,657 MORE GENERALLY, TRYING TO THINK 2797 01:47:38,657 --> 01:47:40,292 ABOUT WHAT WE KNOW ABOUT OTHER 2798 01:47:40,292 --> 01:47:42,828 FIELDS AND WHAT THAT MEANS FOR 2799 01:47:42,828 --> 01:47:44,964 LIKE BUILDING THAT SOCIAL 2800 01:47:44,964 --> 01:47:47,099 CONTEXT, WHAT THAT MEANS FOR 2801 01:47:47,099 --> 01:47:48,200 HEALTHCARE EXPERIENCE. 2802 01:47:48,200 --> 01:47:50,903 BUT IT'S LIKE ON TOP OF THAT 2803 01:47:50,903 --> 01:47:53,639 PROBABLY THE FIRST STEP IS LIKE 2804 01:47:53,639 --> 01:47:55,174 ENGAGING COMMUNITY AND SO LIKE 2805 01:47:55,174 --> 01:47:58,777 ESPECIALLY WHEN YOU THINK ABOUT 2806 01:47:58,777 --> 01:48:01,747 INTERVENTION DEVELOPMENT, I 2807 01:48:01,747 --> 01:48:02,514 THINK THE SUCCESSFUL STUDIES 2808 01:48:02,514 --> 01:48:05,651 HAVE BEEN ABLE TO MAKE A 2809 01:48:05,651 --> 01:48:08,087 DIFFERENCE, MORE LOCAL LEVEL, 2810 01:48:08,087 --> 01:48:10,155 LIKE CARDIOVASCULAR HEALTH HAVE 2811 01:48:10,155 --> 01:48:11,857 PARTNERED WITH CAPTIVE AUDIENCE 2812 01:48:11,857 --> 01:48:13,092 OR CAPTIVE STAKEHOLDERS THAT 2813 01:48:13,092 --> 01:48:14,560 HAVE A DIRECT CONNECTION TO 2814 01:48:14,560 --> 01:48:16,962 PEOPLE THAT EXPERIENCE THESE 2815 01:48:16,962 --> 01:48:20,132 DISPARITIES AND SO IT'S KIND 2816 01:48:20,132 --> 01:48:24,970 OF -- IT WOULD MAKE SENSE TO GO 2817 01:48:24,970 --> 01:48:25,804 BACK TO DISCUSSIONS ABOUT 2818 01:48:25,804 --> 01:48:26,905 AWARENESS, VACCINATION CAMPAIGNS 2819 01:48:26,905 --> 01:48:29,742 AND THINGS LIKE THAT, MAKE THE 2820 01:48:29,742 --> 01:48:31,710 CONNECTION TO SEPSIS AS RELATED 2821 01:48:31,710 --> 01:48:35,714 TO THINGS LIKE YOUR FLU VACCINE, 2822 01:48:35,714 --> 01:48:36,649 STREP, PNEUMONIA VACCINES, 2823 01:48:36,649 --> 01:48:38,751 THINGS WE DO FOR CHILDREN SHOULD 2824 01:48:38,751 --> 01:48:40,953 BE IMPORTANT FOR ADULTS, LIKE 2825 01:48:40,953 --> 01:48:42,488 THAT KIND OF DISCUSSION. 2826 01:48:42,488 --> 01:48:44,790 SO THERE ARE MANY OPPORTUNITIES. 2827 01:48:44,790 --> 01:48:46,759 THE PROBLEM IS COMPLICATED, MANY 2828 01:48:46,759 --> 01:48:49,295 OPPORTUNITIES TO GET STARTED 2829 01:48:49,295 --> 01:48:53,666 LITERALLY ANYWHERE, IT WAS A 2830 01:48:53,666 --> 01:48:57,369 GREAT QUESTION. 2831 01:48:57,369 --> 01:49:00,773 >> I THINK TOM BELLI AT MICHIGAN 2832 01:49:00,773 --> 01:49:03,609 WORKS WITH MARIE HUFF, SOCIAL 2833 01:49:03,609 --> 01:49:06,345 EPIDEMIOLOGIST, DR. RUDD SHARED 2834 01:49:06,345 --> 01:49:09,315 WORK BY NANCY KRIEGER, SOCIAL 2835 01:49:09,315 --> 01:49:11,617 EPIDEMIOLOGIST, IN A DIFFERENT 2836 01:49:11,617 --> 01:49:12,384 FIELD FOCUSING ON ONCOLOGY BUT 2837 01:49:12,384 --> 01:49:16,655 THAT MIGHT BE A GOOD MODEL. 2838 01:49:16,655 --> 01:49:18,824 THERE ARE DIVISIONS, FOR EXAMPLE 2839 01:49:18,824 --> 01:49:22,227 HOPKINS DIVISION OF PULMONARY 2840 01:49:22,227 --> 01:49:24,963 AND CRITICAL CARE HIRED KATIE, A 2841 01:49:24,963 --> 01:49:26,165 SOCIOLOGIST, INTO THEIR 2842 01:49:26,165 --> 01:49:27,499 DIVISION, MODELS OF WAYS THAT 2843 01:49:27,499 --> 01:49:30,436 COULD BE SUCCESSFUL. 2844 01:49:30,436 --> 01:49:33,172 >> I THINK WE'RE NEARING OUR 2845 01:49:33,172 --> 01:49:33,372 BREAK. 2846 01:49:33,372 --> 01:49:36,575 WE HAVE TIME FOR ONE MORE 2847 01:49:36,575 --> 01:49:37,543 COMMENT OR QUESTION. 2848 01:49:37,543 --> 01:49:39,712 >> THANK YOU SO MUCH FOR THE 2849 01:49:39,712 --> 01:49:40,179 WONDERFUL TALKS. 2850 01:49:40,179 --> 01:49:42,381 I HAVE A COMMENT AND QUESTION. 2851 01:49:42,381 --> 01:49:46,318 WE ALL SHARE THE STRUGGLE WITH 2852 01:49:46,318 --> 01:49:47,853 SEPSIS DEFINITIONS. 2853 01:49:47,853 --> 01:49:50,789 THEY ARE DIFFICULT IF YOU DON'T 2854 01:49:50,789 --> 01:49:52,891 HAVE, YOU KNOW, AN AMAZING 2855 01:49:52,891 --> 01:49:54,560 DEFINITION, THAT'S WHAT YOU 2856 01:49:54,560 --> 01:49:54,860 NEED. 2857 01:49:54,860 --> 01:49:59,465 I CAN TELL YOU FOR PEDIATRIC 2858 01:49:59,465 --> 01:50:01,033 SEPSIS WORLD WHICH IS RELEVANT 2859 01:50:01,033 --> 01:50:05,270 TO MY WORK, WE HAVE THE PHOENIX 2860 01:50:05,270 --> 01:50:07,906 CRITERIA BUT WE'RE WORKING NOW 2861 01:50:07,906 --> 01:50:11,076 AS A GROUP WORKING ON DEFINITION 2862 01:50:11,076 --> 01:50:11,844 FOR EMERGENCY SETTINGS WHICH 2863 01:50:11,844 --> 01:50:16,949 MEANS WE'LL TRY TO USE EARLIER 2864 01:50:16,949 --> 01:50:20,252 DATA TO HELP, YOU KNOW, WITH 2865 01:50:20,252 --> 01:50:21,787 DEFINING AND STUDYING SEPSIS. 2866 01:50:21,787 --> 01:50:26,291 ONE QUESTION I HAVE, IT WAS THE 2867 01:50:26,291 --> 01:50:32,631 FIRST TALK, ABOUT SUBTYPES AND 2868 01:50:32,631 --> 01:50:34,366 THE COMORBIDITIES IN DIFFERENT 2869 01:50:34,366 --> 01:50:36,969 PATIENT GROUPS, ARE THERE ANY 2870 01:50:36,969 --> 01:50:40,639 STUDIES ABOUT POTENTIALLY SOME 2871 01:50:40,639 --> 01:50:44,042 OF THOSE COMORBIDITIES SHARING 2872 01:50:44,042 --> 01:50:45,677 SPECIFIC PATHWAYS OR TARGETS? 2873 01:50:45,677 --> 01:50:47,880 BECAUSE IF WE'RE TRYING TO 2874 01:50:47,880 --> 01:50:48,847 TACKLE RACIAL DISPARITIES MAYBE 2875 01:50:48,847 --> 01:50:50,282 WE SHOULD LOOK INTO 2876 01:50:50,282 --> 01:50:51,350 COMORBIDITIES THEMSELVES AND SEE 2877 01:50:51,350 --> 01:50:54,086 IF THERE ARE ANY COMMONALITIES 2878 01:50:54,086 --> 01:50:59,024 THERE THAT WE COULD TARGET WITH 2879 01:50:59,024 --> 01:50:59,324 TREATMENTS. 2880 01:50:59,324 --> 01:51:02,628 >> GREAT QUESTION. 2881 01:51:02,628 --> 01:51:04,496 I THINK THAT WAS ONE OF THE 2882 01:51:04,496 --> 01:51:08,233 STUDIES I SHARED THAT HAD USED 2883 01:51:08,233 --> 01:51:11,069 THE MIMIC DATA, LATENT CLASS 2884 01:51:11,069 --> 01:51:12,838 ANALYSIS TO IDENTIFY DIFFERENT 2885 01:51:12,838 --> 01:51:14,540 CLASSES OF PATIENTS ADMITTED TO 2886 01:51:14,540 --> 01:51:16,208 ICUs IN THE U.S. AND THEN 2887 01:51:16,208 --> 01:51:18,310 LOOKED TO SEE ASSOCIATION OF 2888 01:51:18,310 --> 01:51:20,813 THOSE CLASSES WITH RISK FOR 2889 01:51:20,813 --> 01:51:23,549 ORGAN FAILURE AND SEPSIS AND 2890 01:51:23,549 --> 01:51:24,316 RELATED MORTALITY. 2891 01:51:24,316 --> 01:51:28,720 I AM NOT AWARE OF STUDIES THAT 2892 01:51:28,720 --> 01:51:30,889 HAVE LIKE WATCHED THAT FULL 2893 01:51:30,889 --> 01:51:33,292 CHAIN OF LIKE FROM ASSOCIATION 2894 01:51:33,292 --> 01:51:35,928 TO CAUSATION OF FIRST 2895 01:51:35,928 --> 01:51:38,363 IDENTIFYING PEOPLE THAT CLUSTER 2896 01:51:38,363 --> 01:51:40,199 BASED ON BASELINE RISK FACTORS, 2897 01:51:40,199 --> 01:51:42,067 PARTICULARLY I THINK YOU'RE 2898 01:51:42,067 --> 01:51:43,569 ASKING ABOUT MEDICAL BASELINE 2899 01:51:43,569 --> 01:51:44,503 RISK FACTORS. 2900 01:51:44,503 --> 01:51:47,973 AND THEN LOOKED TO SEE WHETHER 2901 01:51:47,973 --> 01:51:48,841 THERE'S ASSOCIATION IN THE 2902 01:51:48,841 --> 01:51:50,676 PHYSIOLOGY OF THOSE RISK FACTORS 2903 01:51:50,676 --> 01:51:56,081 AND THEN SEE IF THAT MAPS ON TO 2904 01:51:56,081 --> 01:51:57,382 SOME PHENOTYPES OF SEPSIS, MAYBE 2905 01:51:57,382 --> 01:51:59,251 IT'S NOT IMPORTANT THEY DO MAP 2906 01:51:59,251 --> 01:51:59,485 ON. 2907 01:51:59,485 --> 01:52:01,653 MAYBE IT'S JUST ENOUGH TO KNOW 2908 01:52:01,653 --> 01:52:02,754 THERE'S THAT SHARED PHYSIOLOGY 2909 01:52:02,754 --> 01:52:05,491 WE MIGHT BE ABLE TO INTERVENE 2910 01:52:05,491 --> 01:52:05,691 UPON. 2911 01:52:05,691 --> 01:52:07,559 I WOULD DEFER TO SOME OF MY 2912 01:52:07,559 --> 01:52:09,761 COLLEAGUES THAT HAVE MORE 2913 01:52:09,761 --> 01:52:10,863 TRANSLATIONAL EXPERTISE THAT 2914 01:52:10,863 --> 01:52:12,831 REALLY UNDERSTAND MORE OF THE 2915 01:52:12,831 --> 01:52:14,600 INFLAMMATORY PATHWAYS OR LOOKING 2916 01:52:14,600 --> 01:52:16,969 AT MICROVASCULAR CHANGES FOR 2917 01:52:16,969 --> 01:52:18,203 EXAMPLE, I THINK SOME THINGS 2918 01:52:18,203 --> 01:52:21,473 HAVE BEEN PROPOSED BUT I'M NOT 2919 01:52:21,473 --> 01:52:24,877 AWARE OF CLEAR CONCRETE EVIDENCE 2920 01:52:24,877 --> 01:52:27,746 THAT IS SHOWING US SHARED 2921 01:52:27,746 --> 01:52:31,216 PATHOPHYSIOLOGY BETWEEN THESE 2922 01:52:31,216 --> 01:52:31,917 REALLY IMPORTANT COMORBID 2923 01:52:31,917 --> 01:52:32,751 CONDITIONS PUTTING PEOPLE AT 2924 01:52:32,751 --> 01:52:38,357 RISK. 2925 01:52:38,357 --> 01:52:38,991 >> THANK YOU. 2926 01:52:38,991 --> 01:52:41,193 >> ANYONE ELSE WANTS TO TACKLE 2927 01:52:41,193 --> 01:52:41,393 THAT? 2928 01:52:41,393 --> 01:52:43,262 I'LL AGREE COMPLETELY WITH WHAT 2929 01:52:43,262 --> 01:52:51,770 KRISTINA SAID. 2930 01:52:51,770 --> 01:53:01,747 I DON'T KNOW PATHOPHYSIOLOGY 2931 01:53:01,747 --> 01:53:04,917 LINKS FOR ORGAN DYSFUNCTION. 2932 01:53:04,917 --> 01:53:06,785 CHRONIC LUNG DISEASE LEADS TO 2933 01:53:06,785 --> 01:53:08,654 RESPIRATORY FAILURE BUT WHETHER 2934 01:53:08,654 --> 01:53:10,489 PATHWAYS INVOLVED ARE THE SAME 2935 01:53:10,489 --> 01:53:11,356 BIOLOGICALLY FOR INSTANCE I 2936 01:53:11,356 --> 01:53:21,800 DON'T KNOW THAT WE KNOW. 2937 01:53:24,570 --> 01:53:26,471 >> THINK YOU ALL FOR A GREAT 2938 01:53:26,471 --> 01:53:26,972 DISCUSSION. 2939 01:53:26,972 --> 01:53:28,473 DEEP AND I WOULD LIKE TO THANK 2940 01:53:28,473 --> 01:53:31,276 THE SPEAKERS IN THE FIRST 2941 01:53:31,276 --> 01:53:31,510 SESSION. 2942 01:53:31,510 --> 01:53:33,545 THIS PUTS AN END TO SESSION 1. 2943 01:53:33,545 --> 01:53:38,083 I WANT TO TURN IT OVER TO NITIN 2944 01:53:38,083 --> 01:53:41,954 AND THANK ALL THE SPEAKERS FOR A 2945 01:53:41,954 --> 01:53:43,255 FANTASTIC TALK. 2946 01:53:43,255 --> 01:53:43,789 >> THANK YOU. 2947 01:53:43,789 --> 01:53:45,958 IT WAS A GREAT DISCUSSION. 2948 01:53:45,958 --> 01:53:48,126 I HOPE THAT EVERYBODY HAD A 2949 01:53:48,126 --> 01:53:51,964 CHANCE TO TAKE AWAY SOME 2950 01:53:51,964 --> 01:53:53,632 CRITICAL MESSAGES FROM THIS 2951 01:53:53,632 --> 01:53:53,832 PANEL. 2952 01:53:53,832 --> 01:53:55,601 LET'S TAKE A QUICK BREAK. 2953 01:53:55,601 --> 01:54:00,839 WE WERE SUPPOSED HAVE THE BREAK 2954 01:54:00,839 --> 01:54:02,808 FROM 11:15 BUT IT SHOULD BE 2955 01:54:02,808 --> 01:54:08,213 ENOUGH TO GRAB COFFEE OR LUNCH 2956 01:54:08,213 --> 01:54:08,647 QUICKLY. 2957 01:54:08,647 --> 01:54:10,549 WE'LL RECONVENE A COUPLE MINUTES 2958 01:54:10,549 --> 01:54:21,076 BEFORE 12:15 SO WE CAN GET STARTED. 2959 01:54:21,076 --> 01:54:30,885 I WOULD LIKE TO WELCOME US. 2960 01:54:30,885 --> 01:54:38,360 THIS IS GOING TO BE AN EQUALLY 2961 01:54:38,360 --> 01:54:42,530 EXCITING SESSION, AS SESSION 1. 2962 01:54:42,530 --> 01:54:44,499 >> THANKS, NITIN, FOR INVITING 2963 01:54:44,499 --> 01:54:44,833 US. 2964 01:54:44,833 --> 01:54:48,636 CAN EVERYONE HEAR US? 2965 01:54:48,636 --> 01:54:50,839 WE HAVE A NICE SESSION LINED UP, 2966 01:54:50,839 --> 01:54:56,244 FOUR SPEAKERS, FOCUSING ON BASIC 2967 01:54:56,244 --> 01:54:57,045 TRANSLATIONAL ASPECT OF 2968 01:54:57,045 --> 01:55:07,489 IMMUNOTHROMBOSIS, RANGING 2969 01:55:09,357 --> 01:55:11,593 FROM -- A SESSION ON WHERE WE 2970 01:55:11,593 --> 01:55:13,595 STAND ABOUT THE THERAPY AND 2971 01:55:13,595 --> 01:55:15,196 CLINICAL TRIALS IN SEPSIS, WHY 2972 01:55:15,196 --> 01:55:19,501 THINGS HAVE FAILED, WHAT HAS 2973 01:55:19,501 --> 01:55:21,236 FAILED, THAT WOULD BE THE LAST 2974 01:55:21,236 --> 01:55:23,905 TALK OF THE SESSION. 2975 01:55:23,905 --> 01:55:29,010 SO, WITH MY GREAT PLEASURE I 2976 01:55:29,010 --> 01:55:30,879 WOULD LIKE TO INTRODUCE THE 2977 01:55:30,879 --> 01:55:33,415 DISTINGUISHED PROFESSOR OF 2978 01:55:33,415 --> 01:55:36,718 MEDICINE FROM UNC CHAPEL, AND HE 2979 01:55:36,718 --> 01:55:42,056 HAS DECADES OF EXPERIENCE IN 2980 01:55:42,056 --> 01:55:43,691 STUDYING SPECIFICALLY HOW EXTRA 2981 01:55:43,691 --> 01:55:47,095 VASCULARS CONTRIBUTE IN SEPSIS 2982 01:55:47,095 --> 01:55:48,396 AND OUTSIDE OF SEPSIS, HERE TO 2983 01:55:48,396 --> 01:55:51,332 SHARE THE WEALTH OF KNOWLEDGE. 2984 01:55:51,332 --> 01:55:56,171 PLEASE, THANK YOU VERY MUCH. 2985 01:55:56,171 --> 01:55:57,472 >> I'D LIKE TO THANK THE 2986 01:55:57,472 --> 01:55:58,907 ORGANIZERS FOR INVITING ME. 2987 01:55:58,907 --> 01:56:03,178 I'M GOING TO TALK ABOUT 2988 01:56:03,178 --> 01:56:03,845 COAGULATION, IMMUNOTHROMBOSIS, 2989 01:56:03,845 --> 01:56:05,146 EXTRACELLULAR VESICLES AND 2990 01:56:05,146 --> 01:56:05,580 SEPSIS. 2991 01:56:05,580 --> 01:56:06,114 NEXT SLIDE PLEASE. 2992 01:56:06,114 --> 01:56:09,517 SO THIS IS THE OUTLINE OF MY 2993 01:56:09,517 --> 01:56:09,851 PRESENTATION. 2994 01:56:09,851 --> 01:56:12,353 I'M GOING TO GIVE YOU AN 2995 01:56:12,353 --> 01:56:13,521 INTRODUCTION TO COAGULATION. 2996 01:56:13,521 --> 01:56:17,926 AND THEN THE DEFINITION OF 2997 01:56:17,926 --> 01:56:19,360 IMMUNOTHROMBOSIS, INTRODUCE 2998 01:56:19,360 --> 01:56:21,296 EXTRACELLULAR VESICLES, EVS, AND 2999 01:56:21,296 --> 01:56:25,633 GO THROUGH HISTORY ON THE 3000 01:56:25,633 --> 01:56:28,036 LESSONS WE'VE LEARNED FROM E. 3001 01:56:28,036 --> 01:56:31,873 COLI SEPSIS, EFFECT OF 3002 01:56:31,873 --> 01:56:33,374 ANTICOAGULANTS, MODELS OF SEPTIC 3003 01:56:33,374 --> 01:56:39,948 PATIENTS, AND TALK ABOUT MY 3004 01:56:39,948 --> 01:56:42,083 FAVORITE MOLECULE, THE ROLE OF 3005 01:56:42,083 --> 01:56:47,856 TISSUE MONOCYTES, AND MOUSE 3006 01:56:47,856 --> 01:56:50,792 MODELS AND ENDOTOXEMIA AND 3007 01:56:50,792 --> 01:56:51,092 CONCLUSIONS. 3008 01:56:51,092 --> 01:56:53,995 THIS IS A SIMPLIFIED VERSION OF 3009 01:56:53,995 --> 01:56:56,464 THE CASCADE, ESSENTIAL FOR 3010 01:56:56,464 --> 01:56:59,000 HEMOSTASIS BUT CAUSES 3011 01:56:59,000 --> 01:57:01,636 THROMBOSIS. 3012 01:57:01,636 --> 01:57:10,478 TWO PATHWAYS, ONE IS EXTRINSIC. 3013 01:57:10,478 --> 01:57:15,450 I WORK ON TISSUE FACTOR, 3014 01:57:15,450 --> 01:57:19,387 CLOTTING CASCADE. 3015 01:57:19,387 --> 01:57:25,660 THERE ARE THREE MAJOR PATHWAYS, 3016 01:57:25,660 --> 01:57:29,430 IN ORANGE INHIBITS PROTEIN 3017 01:57:29,430 --> 01:57:30,064 SYSTEM THAT CLEAVES, FACTORINGS 3018 01:57:30,064 --> 01:57:40,475 8 AND 9, AND THAT'S ALSO 3019 01:57:40,775 --> 01:57:41,576 THROMBOMODULIN, AND 3020 01:57:41,576 --> 01:57:41,910 ANTI-THROMBIN. 3021 01:57:41,910 --> 01:57:46,281 THAT WILL COME UP IN MY TALK 3022 01:57:46,281 --> 01:57:46,814 LATER. 3023 01:57:46,814 --> 01:57:47,482 NEXT PLEASE. 3024 01:57:47,482 --> 01:57:49,817 SO, I THOUGHT IT WAS IMPORTANT 3025 01:57:49,817 --> 01:57:58,026 TO DEFINE WHAT I DEFINE 3026 01:57:58,026 --> 01:57:59,327 IMTHROMBOSIS VERSUS 3027 01:57:59,327 --> 01:58:00,695 THROMBOINFLAMMATION. 3028 01:58:00,695 --> 01:58:01,396 IMMUNE CELLS CONTRIBUTE TO 3029 01:58:01,396 --> 01:58:08,269 THROMBOSIS WITHIN A BLOOD 3030 01:58:08,269 --> 01:58:11,873 VESSEL. 3031 01:58:11,873 --> 01:58:15,376 THIS WAS FIRST COINED IN 2013 BY 3032 01:58:15,376 --> 01:58:20,848 ENGELMANN AND MASS BEGGAR. 3033 01:58:20,848 --> 01:58:22,483 THE RIGHT-HAND SIDE IS 3034 01:58:22,483 --> 01:58:23,384 NEUTROPHIL EXTRACELLULAR 3035 01:58:23,384 --> 01:58:29,057 TRAPPING RELEASED FROM A 3036 01:58:29,057 --> 01:58:29,357 NEUTROPHIL. 3037 01:58:29,357 --> 01:58:31,125 NEXT PLEASE. 3038 01:58:31,125 --> 01:58:33,161 THERE IS THROMBOINFLAMMATION, 3039 01:58:33,161 --> 01:58:34,662 THAT DESCRIBED PROCESS WHERE 3040 01:58:34,662 --> 01:58:36,631 INFLAMMATION OF THROMBUS LEADS 3041 01:58:36,631 --> 01:58:37,599 TO INFLAMMATION AND RECRUITMENT 3042 01:58:37,599 --> 01:58:40,568 OF IMMUNE CELLS. 3043 01:58:40,568 --> 01:58:42,136 EXAMPLE IS ISCHEMIC STROKE. 3044 01:58:42,136 --> 01:58:44,405 THROMBUS COMES FIRST, BLOCKS THE 3045 01:58:44,405 --> 01:58:46,040 BLOOD VESSEL, SECONDARILY LEADS 3046 01:58:46,040 --> 01:58:50,078 TO INFLAMMATION. 3047 01:58:50,078 --> 01:58:53,615 NEXT SLIDE PLEASE. 3048 01:58:53,615 --> 01:58:56,718 EXTRACELLULAR VESICLES ARE 3049 01:58:56,718 --> 01:58:57,318 MICROPARTICLES, MICROVESICLES 3050 01:58:57,318 --> 01:59:01,055 RELEASED FROM CELLS, A VARIETY 3051 01:59:01,055 --> 01:59:07,595 OF SIZES BUT THE GLOBAL TERM IS 3052 01:59:07,595 --> 01:59:09,030 EXTRACELLULAR VESICLES, EVS. 3053 01:59:09,030 --> 01:59:12,767 SO, IMPORTANT COMPONENTS OF THE 3054 01:59:12,767 --> 01:59:15,503 EXTRACELLULAR VESSELS ARE PRO 3055 01:59:15,503 --> 01:59:18,239 COAGULANT ACTIVITY, THERE ARE 3056 01:59:18,239 --> 01:59:19,841 HIGH LEVELS OF PS-POSITIVE 3057 01:59:19,841 --> 01:59:22,310 EXTRACELLULAR VESICLES IN THE 3058 01:59:22,310 --> 01:59:32,487 BLOOD, MODEST LEVEL OF PRO 3059 01:59:32,487 --> 01:59:39,494 COAGULANT EVS. 3060 01:59:39,494 --> 01:59:45,600 A PHOSPHOLIPID BINDS, MORE 3061 01:59:45,600 --> 01:59:45,933 PROCOAGULANT. 3062 01:59:45,933 --> 01:59:48,102 THE EXTRACELLULAR VESICLES WE'RE 3063 01:59:48,102 --> 01:59:50,171 INTERESTED IN ARE IT POSITIVE 3064 01:59:50,171 --> 01:59:50,972 EXTRACELLULAR VESICLES, ALSO 3065 01:59:50,972 --> 01:59:53,141 HAVE PS, THEY ARE NOT DETECTED 3066 01:59:53,141 --> 01:59:54,909 IN HEALTHY INDIVIDUALS BUT 3067 01:59:54,909 --> 01:59:56,110 INCREASES IN DIFFERENT DISEASE 3068 01:59:56,110 --> 01:59:58,780 STATES SUCH AS SEPSIS AND ARE 3069 01:59:58,780 --> 01:59:59,747 RELEASED FROM ACTIVATED 3070 01:59:59,747 --> 02:00:02,383 MONOCYTES, ALSO FROM TUMOR 3071 02:00:02,383 --> 02:00:03,151 CELLS. 3072 02:00:03,151 --> 02:00:05,119 NEXT PLEASE. 3073 02:00:05,119 --> 02:00:07,955 SO THIS IS SUMMARY FROM FLETCHER 3074 02:00:07,955 --> 02:00:10,792 TAYLOR'S WORK, MODELS OF SEPSIS. 3075 02:00:10,792 --> 02:00:13,695 AND WHAT THEY DIVIDED THESE 3076 02:00:13,695 --> 02:00:16,831 SEPSIS PHASES INTO, TWO PHASES, 3077 02:00:16,831 --> 02:00:19,333 FIRST BETWEEN ZERO AND EIGHT 3078 02:00:19,333 --> 02:00:23,037 HOURS, YOU CAN SEE INCREASE IN 3079 02:00:23,037 --> 02:00:24,138 TISSUE FACTOR EXPRESSION, 3080 02:00:24,138 --> 02:00:26,007 DYSREGULATION OF THE 3081 02:00:26,007 --> 02:00:26,541 ANTICOAGULANT SYSTEM, 3082 02:00:26,541 --> 02:00:27,742 ENDOTHELIAL CELL DYSFUNCTION, 3083 02:00:27,742 --> 02:00:30,178 THAT LEADS TO ACTIVATION OF 3084 02:00:30,178 --> 02:00:31,913 COAGULATION THAT ULTIMATELY 3085 02:00:31,913 --> 02:00:34,449 LEADS TO SHOCK AND DISSEMINATED 3086 02:00:34,449 --> 02:00:36,451 INTRAVASCULAR COAGULATION. 3087 02:00:36,451 --> 02:00:37,518 NEXT PLEASE. 3088 02:00:37,518 --> 02:00:39,787 BETWEEN NINE AND 24 HOURS, THERE 3089 02:00:39,787 --> 02:00:42,423 IS THE SECOND PHASE WHICH IS 3090 02:00:42,423 --> 02:00:46,027 ASSOCIATED WITH RELEASE OF 3091 02:00:46,027 --> 02:00:51,332 HISTONES, REPERFUSION INJURY, 3092 02:00:51,332 --> 02:00:52,633 OXIDATIVE STRESS TO ULTIMATELY 3093 02:00:52,633 --> 02:00:54,702 LEADS TO ORGAN FAILURE. 3094 02:00:54,702 --> 02:00:55,803 NEXT PLEASE. 3095 02:00:55,803 --> 02:01:00,641 SO, WHAT IS EFFECT OF 3096 02:01:00,641 --> 02:01:01,776 ANTICOAGULANTS IN SEPTIC 3097 02:01:01,776 --> 02:01:02,043 PATIENTS? 3098 02:01:02,043 --> 02:01:03,611 WITH ANIMAL MODELS EVERYTHING IS 3099 02:01:03,611 --> 02:01:05,012 SUCCESSFUL BECAUSE YOU CAN 3100 02:01:05,012 --> 02:01:07,749 INTERVENE BEFORE THE DISEASE 3101 02:01:07,749 --> 02:01:09,617 HAPPENS, SO IF YOU SEE 3102 02:01:09,617 --> 02:01:11,452 PROTECTIVE OF BABOONS FROM 3103 02:01:11,452 --> 02:01:13,755 DEATH, TISSUE FACTOR PATHWAY 3104 02:01:13,755 --> 02:01:19,127 INHIBITOR PROTECTIVE, REDUCE THE 3105 02:01:19,127 --> 02:01:20,628 IL-6 LEVELS, ANTI-THROMBIN WAS 3106 02:01:20,628 --> 02:01:23,030 PROTECTED IN BABOON MODEL. 3107 02:01:23,030 --> 02:01:26,667 IF YOU MOVE TO, NEXT PLEASE, THE 3108 02:01:26,667 --> 02:01:28,803 HUMANS, YOU'RE FAMILIAR WITH APC 3109 02:01:28,803 --> 02:01:30,438 TRIAL THAT REDUCED ALL-CAUSE 3110 02:01:30,438 --> 02:01:34,542 MORTALITY BY 6.1% IN SEVERE 3111 02:01:34,542 --> 02:01:35,143 SEPSIS. 3112 02:01:35,143 --> 02:01:37,812 TFPI WAS NOT SUCCESSFUL AND WAS 3113 02:01:37,812 --> 02:01:40,448 ASSOCIATED WITH INCREASED 3114 02:01:40,448 --> 02:01:40,882 BLEEDING. 3115 02:01:40,882 --> 02:01:42,950 ANTI-THROMBIN DID NOT AFFECT 3116 02:01:42,950 --> 02:01:44,485 ALL-CAUSE MORTALITY. 3117 02:01:44,485 --> 02:01:46,354 IN FACT COMBINING ANTI-THROMBIN 3118 02:01:46,354 --> 02:01:51,726 WITH HEPARIN INCREASED BLEEDING. 3119 02:01:51,726 --> 02:01:54,996 NEXT PLEASE. 3120 02:01:54,996 --> 02:01:56,864 SO, AN INTERESTING MOLECULE IN A 3121 02:01:56,864 --> 02:01:59,167 TRIAL, IT DID NOT REDUCE 3122 02:01:59,167 --> 02:02:00,802 ALL-CAUSE MORTALITY IN SEPSIS, 3123 02:02:00,802 --> 02:02:04,872 AND WHAT WAS CALLED SCHOLAR 3124 02:02:04,872 --> 02:02:06,274 TRIAL, NEXT PLEASE. 3125 02:02:06,274 --> 02:02:16,818 IF WE LOOK AT EFFECT OF SOLUBLE 3126 02:02:19,587 --> 02:02:24,659 THROMBO MODULIN, COMPARED WITH 3127 02:02:24,659 --> 02:02:27,395 HEPARIN, ANOTHER STUDY IN 2016 3128 02:02:27,395 --> 02:02:28,930 REDUCED THE IN-HOSPITAL 3129 02:02:28,930 --> 02:02:31,799 MORTALITY, SMALL STUDY WAS NOT 3130 02:02:31,799 --> 02:02:34,535 POSITIVE, BUT THEN IN A POST HOC 3131 02:02:34,535 --> 02:02:36,704 ANALYSIS OF THE TRIAL BENEFITS 3132 02:02:36,704 --> 02:02:40,107 WITH HIGHER PATIENTS WITH HIGHER 3133 02:02:40,107 --> 02:02:42,610 LEVELS OF THROMBIN, 3134 02:02:42,610 --> 02:02:44,712 ANTI-THROMBIN COMPLEXES, OTHERS 3135 02:02:44,712 --> 02:02:50,151 WITH LOWER LEVELS, AND IN FACT A 3136 02:02:50,151 --> 02:02:53,988 META-ANALYSIS OF THREE 3137 02:02:53,988 --> 02:02:55,756 RANDOMIZED TRIALS SHOWED THE 3138 02:02:55,756 --> 02:02:58,926 SOLUBLE REDUCED 28-DAY MORTALITY 3139 02:02:58,926 --> 02:03:02,763 WITH SEPSIS COAGULOPATHY BUT NOT 3140 02:03:02,763 --> 02:03:03,231 WITHOUT. 3141 02:03:03,231 --> 02:03:05,166 NEXT SLIDE PLEASE. 3142 02:03:05,166 --> 02:03:07,368 SO I THINK DATA IS INTERESTING 3143 02:03:07,368 --> 02:03:09,804 BECAUSE WHAT IT SHOWS HERE IS AS 3144 02:03:09,804 --> 02:03:11,906 YOU INCREASE THE COAGULOPATHY 3145 02:03:11,906 --> 02:03:14,876 FROM LEFT TO RIGHT, THERE'S 3146 02:03:14,876 --> 02:03:15,943 INCREASE IN MORTALITY, AND THEN 3147 02:03:15,943 --> 02:03:18,579 WHEN THE TWO GROUPS ARE TREATED 3148 02:03:18,579 --> 02:03:27,455 WITH EITHER THE SOLUBLE THROMBO 3149 02:03:27,455 --> 02:03:27,688 M 3150 02:03:27,688 --> 02:03:28,923 ODULIN OR PLACEBO, GREAT 3151 02:03:28,923 --> 02:03:32,627 IN THOSE WITH HIGHEST LEVEL OF 3152 02:03:32,627 --> 02:03:34,662 THE COMPLEX. 3153 02:03:34,662 --> 02:03:37,565 IN CONTRAST A COMMON MARKER 3154 02:03:37,565 --> 02:03:38,766 FOREACTIVATION COAGULATION 3155 02:03:38,766 --> 02:03:40,735 THERE'S NO RELATIONSHIP AT ALL, 3156 02:03:40,735 --> 02:03:42,470 AND THAT'S PROBABLY BECAUSE 3157 02:03:42,470 --> 02:03:46,908 DURING SEPSIS THERE'S INCREASE 3158 02:03:46,908 --> 02:03:50,144 IN INHIBITOR 1 BUT WOULD PREVENT 3159 02:03:50,144 --> 02:03:53,014 RELEASE OF THE D-DIMER FROM 3160 02:03:53,014 --> 02:03:54,548 CROSS-LINKED FIBRIN. 3161 02:03:54,548 --> 02:03:55,216 NEXT PLEASE. 3162 02:03:55,216 --> 02:03:57,485 WHAT ABOUT THE USE OF 3163 02:03:57,485 --> 02:03:59,987 ANTICOAGULANTS TO TREAT SEPSIS 3164 02:03:59,987 --> 02:04:06,227 PATIENTS AND PATIENTS WITH VIC? 3165 02:04:06,227 --> 02:04:06,427 NEXT. 3166 02:04:06,427 --> 02:04:07,762 APC WAS APPROVED IN 2001, FOR 3167 02:04:07,762 --> 02:04:09,196 TREATMENT OF PATIENTS WITH 3168 02:04:09,196 --> 02:04:11,065 SEVERE SEPSIS BUT WITHDRAWN FROM 3169 02:04:11,065 --> 02:04:14,001 THE MARKET IN 2011 DUE TO LACK 3170 02:04:14,001 --> 02:04:18,272 OF EFFICACY. 3171 02:04:18,272 --> 02:04:18,472 NEXT. 3172 02:04:18,472 --> 02:04:19,907 SO SOLUBLE THROMBOMODULIN HAS 3173 02:04:19,907 --> 02:04:25,046 BEEN USED IN JAPAN FOR 2008 FOR 3174 02:04:25,046 --> 02:04:25,746 TREATMENT INCLUDING 3175 02:04:25,746 --> 02:04:27,682 SEPSIS-INDUCED DIC. 3176 02:04:27,682 --> 02:04:28,049 NEXT. 3177 02:04:28,049 --> 02:04:30,418 SO, A QUESTION IS WHY IS 3178 02:04:30,418 --> 02:04:33,254 CLOTTING SYSTEM ACTIVATED DURING 3179 02:04:33,254 --> 02:04:35,890 MICROBIAL INFECTION? 3180 02:04:35,890 --> 02:04:36,190 NEXT. 3181 02:04:36,190 --> 02:04:37,858 AND CLOTTING IS PART OF THE 3182 02:04:37,858 --> 02:04:42,129 INNATE IMMUNE SYSTEM. 3183 02:04:42,129 --> 02:04:42,530 NEXT. 3184 02:04:42,530 --> 02:04:48,803 SO, THE HORSESHOE CRAB HAS A 3185 02:04:48,803 --> 02:04:50,071 HEMOCYTE RELEASING CLOTTING 3186 02:04:50,071 --> 02:04:51,739 FACTORINGS THAT ENDS UP CAUSING 3187 02:04:51,739 --> 02:04:54,709 A CLOT. 3188 02:04:54,709 --> 02:05:00,514 THAT'S THE BASIS OF THE ASSAY. 3189 02:05:00,514 --> 02:05:04,018 HUMANS HAVE A MONOCYTE, LPS 3190 02:05:04,018 --> 02:05:05,753 ACTIVATES MONOCYTE TO EXPRESS 3191 02:05:05,753 --> 02:05:08,689 TISSUE FACTOR, THAT DOES THE 3192 02:05:08,689 --> 02:05:10,558 SAME AS HEMOCYTE, ACTIVATION OF 3193 02:05:10,558 --> 02:05:11,792 CLOTTING SYSTEM, TO WALL OFF THE 3194 02:05:11,792 --> 02:05:15,396 INFECTION SO IT DOESN'T BECOME 3195 02:05:15,396 --> 02:05:15,696 SYSTEMIC. 3196 02:05:15,696 --> 02:05:16,597 NEXT PLEASE. 3197 02:05:16,597 --> 02:05:22,036 SO THIS IS THE LPS INDUCTION IN 3198 02:05:22,036 --> 02:05:22,703 HUMAN MONOCYTES. 3199 02:05:22,703 --> 02:05:25,973 IT IS ONLY EXPRESSED BY 3200 02:05:25,973 --> 02:05:27,942 MONOCYTES, NOT BY NEUTROPHILS OR 3201 02:05:27,942 --> 02:05:34,215 B CELLS, AND THIS IS A 3202 02:05:34,215 --> 02:05:35,950 HOST/DEFENSE RESPONSE IN 3203 02:05:35,950 --> 02:05:37,151 IMMUNOTHROMBOSIS. 3204 02:05:37,151 --> 02:05:37,351 NEXT. 3205 02:05:37,351 --> 02:05:41,989 WHEN WE ADD LPS TO HUMAN 3206 02:05:41,989 --> 02:05:43,457 MONOCYTES WE GET A TRANSIENT 3207 02:05:43,457 --> 02:05:44,392 INDUCTION ACTIVITY ON THE CELLS 3208 02:05:44,392 --> 02:05:47,128 THAT WOULD LEAD TO ACTIVATION 3209 02:05:47,128 --> 02:05:51,732 CLOTTING IN THE CIRCULATION. 3210 02:05:51,732 --> 02:05:54,335 NEXT PLEASE. 3211 02:05:54,335 --> 02:05:58,839 HERE IS A SUMMARY OF HUMAN AND 3212 02:05:58,839 --> 02:06:01,909 MOUSE MODELS OF ENDOTOXEMIA. 3213 02:06:01,909 --> 02:06:06,280 YES, PEOPLE DO GIVE VERY LOW 3214 02:06:06,280 --> 02:06:09,884 DOSE 4 NANOGRAMS PER KG, TISSUE 3215 02:06:09,884 --> 02:06:12,186 FACTOR INDUCED IN A TIME 3216 02:06:12,186 --> 02:06:13,387 DEPENDENT MANNER SIMILAR TO IN 3217 02:06:13,387 --> 02:06:14,922 VITRO STUDIES I SHOWED 3218 02:06:14,922 --> 02:06:16,123 PREVIOUSLY. 3219 02:06:16,123 --> 02:06:19,326 THERE'S ALSO AN INCREASE IN 3220 02:06:19,326 --> 02:06:21,729 EXTRACELLULAR TISSUE FACTOR 3221 02:06:21,729 --> 02:06:23,931 ACTIVITY THAT IS PEAKING A 3222 02:06:23,931 --> 02:06:25,766 LITTLE LATER THAN INDUCTION AND 3223 02:06:25,766 --> 02:06:29,804 MONOCYTE CONSISTENT WITH RELEASE 3224 02:06:29,804 --> 02:06:37,711 OF TF-POSITIVE EVS FROM 3225 02:06:37,711 --> 02:06:39,880 ACTIVATED NANOSITE. 3226 02:06:39,880 --> 02:06:41,215 FINALLY ACTIVATION OF CLOTTING 3227 02:06:41,215 --> 02:06:41,615 SYSTEM. 3228 02:06:41,615 --> 02:06:50,491 WE USE A MOUSE MODEL OF 3229 02:06:50,491 --> 02:06:51,492 ENDOTOXEMIA. 3230 02:06:51,492 --> 02:06:53,427 WE SEE TIME DEPENDENT INCREASE 3231 02:06:53,427 --> 02:06:54,728 IN ACTIVITY PEAKING AROUND THREE 3232 02:06:54,728 --> 02:06:57,364 TO FOUR HOURS, AROUND WE SEE 3233 02:06:57,364 --> 02:07:00,201 ACTIVATION OF CLOTTING SYSTEM AS 3234 02:07:00,201 --> 02:07:04,705 MEASURED BY INCREASED 3235 02:07:04,705 --> 02:07:05,439 THROMBIN/ANTI-THROMBIN 3236 02:07:05,439 --> 02:07:05,940 COMPLEXES. 3237 02:07:05,940 --> 02:07:06,540 NEXT PLEASE. 3238 02:07:06,540 --> 02:07:08,309 SO WHAT IS THE ROLE OF TISSUE 3239 02:07:08,309 --> 02:07:13,981 FACTOR IN ACTIVATION OF 3240 02:07:13,981 --> 02:07:15,649 COAGULATION AND ENDOTOXEMIA? 3241 02:07:15,649 --> 02:07:19,687 WE KNOW ADMINISTRATION OF 3242 02:07:19,687 --> 02:07:23,624 ANTI-TISSUE FACTOR PROTECTED 3243 02:07:23,624 --> 02:07:24,592 BABOONS IN A MODEL PUBLISHED IN 3244 02:07:24,592 --> 02:07:25,826 1991. 3245 02:07:25,826 --> 02:07:26,393 NEXT. 3246 02:07:26,393 --> 02:07:29,330 AND WE USED GENETIC APPROACH IN 3247 02:07:29,330 --> 02:07:31,198 WHICH WE DELETED TISSUE FACTOR 3248 02:07:31,198 --> 02:07:32,733 GENE IN MYELOID CELLS, REDUCING 3249 02:07:32,733 --> 02:07:35,236 ACTIVATION OF COAGULATION IN A 3250 02:07:35,236 --> 02:07:41,575 MOUSE MODEL OF ENDOTOXEMIA. 3251 02:07:41,575 --> 02:07:43,544 HOW DO MONOCYTES DETECT LPS IN 3252 02:07:43,544 --> 02:07:45,079 THE BLOOD? 3253 02:07:45,079 --> 02:07:48,282 LPS BINDS TO BINDING PROTEIN, 3254 02:07:48,282 --> 02:07:52,686 DELIVERED TO CD14, THAT THEN 3255 02:07:52,686 --> 02:07:55,156 LEADS TO ACTIVATION OF THE 3256 02:07:55,156 --> 02:07:57,358 COMPLEX INDUCTION OF TISSUE 3257 02:07:57,358 --> 02:07:58,325 FACTOR GENE EXPRESSION, 3258 02:07:58,325 --> 02:07:59,960 EXPRESSION OF TISSUE FACTOR ON 3259 02:07:59,960 --> 02:08:02,062 CELL SURFACE. 3260 02:08:02,062 --> 02:08:03,497 NEXT PLEASE. 3261 02:08:03,497 --> 02:08:08,202 SO WE'VE BEEN LOOKING AT THE 3262 02:08:08,202 --> 02:08:10,037 ROLE OF 4 IN INDUCTION OF TISSUE 3263 02:08:10,037 --> 02:08:11,005 FACTOR AND EV RELEASE AND 3264 02:08:11,005 --> 02:08:17,511 COAGULATION IN A MOUSE MODEL OF 3265 02:08:17,511 --> 02:08:19,079 ENDOTOXEMIA, LATE TIME POINTS OF 3266 02:08:19,079 --> 02:08:22,082 8 HOURS. 3267 02:08:22,082 --> 02:08:24,518 WILD TYPES IN GRAY, KNOCKOUTS IN 3268 02:08:24,518 --> 02:08:24,752 ORANGE. 3269 02:08:24,752 --> 02:08:30,758 YOU CAN SEE IF WE DON'T HAVE TLR 3270 02:08:30,758 --> 02:08:32,393 4 THERE'S SEVERE BLUNTING OF 3271 02:08:32,393 --> 02:08:34,461 ACTIVITY. 3272 02:08:34,461 --> 02:08:34,695 NEXT. 3273 02:08:34,695 --> 02:08:37,531 WE ALSO SEE A BLUNTING OF THE 3274 02:08:37,531 --> 02:08:38,632 ACTIVATION OF COAGULATION 3275 02:08:38,632 --> 02:08:41,602 SHOWING THE DETECTION OF THAT 3276 02:08:41,602 --> 02:08:44,872 LPS IS BY THE TLR 4. 3277 02:08:44,872 --> 02:08:45,973 NEXT PLEASE. 3278 02:08:45,973 --> 02:08:48,375 SO, THE NEXT QUESTION WAS DO 3279 02:08:48,375 --> 02:08:50,578 INFLAMMASOMES PLAY A ROLE IN 3280 02:08:50,578 --> 02:08:53,614 ACTIVATION DURING INFECTION? 3281 02:08:53,614 --> 02:08:54,381 NEXT. 3282 02:08:54,381 --> 02:08:56,483 SO, THERE ARE TWO STUDIES. 3283 02:08:56,483 --> 02:08:56,717 NEXT. 3284 02:08:56,717 --> 02:08:59,453 FIRST STUDY YOU'LL HEAR MORE 3285 02:08:59,453 --> 02:09:02,289 ABOUT FROM DR. LEE IN THE NEXT 3286 02:09:02,289 --> 02:09:03,824 PRESENTATION BUT TO INTRODUCE 3287 02:09:03,824 --> 02:09:07,328 IT, WE FOUND THERE WAS AN 3288 02:09:07,328 --> 02:09:09,530 INDUCTION OF TISSUE FACTOR 3289 02:09:09,530 --> 02:09:12,600 EXPRESSION DURING INFLAMMASOME 3290 02:09:12,600 --> 02:09:12,900 ACTIVATION. 3291 02:09:12,900 --> 02:09:14,235 THAT WAS ASSOCIATED WITH RELEASE 3292 02:09:14,235 --> 02:09:17,204 OF EXTRACELLULAR VESICLES THAT 3293 02:09:17,204 --> 02:09:26,313 LED TO DISSEMINATION 3294 02:09:26,313 --> 02:09:30,517 INTRAVASCULAR COAGULATION AND 3295 02:09:30,517 --> 02:09:30,784 LETHALITY. 3296 02:09:30,784 --> 02:09:33,721 THEY SAID THERE WAS INCREASE IN 3297 02:09:33,721 --> 02:09:35,823 EXPOSURE OF THAT MOLECULE I WAS 3298 02:09:35,823 --> 02:09:37,424 TALKING ABOUT EARLIER. 3299 02:09:37,424 --> 02:09:40,694 THAT WAS INCREASING THE TISSUE 3300 02:09:40,694 --> 02:09:42,663 FACTOR ACTIVITY IN A WAY I 3301 02:09:42,663 --> 02:09:44,098 DESCRIBED EARLIER. 3302 02:09:44,098 --> 02:09:46,767 THESE ARE TWO PATHWAYS. 3303 02:09:46,767 --> 02:09:50,337 NEXT PLEASE. 3304 02:09:50,337 --> 02:09:50,904 >> TWO MINUTES REMAINING. 3305 02:09:50,904 --> 02:09:52,339 >> THANK YOU. 3306 02:09:52,339 --> 02:09:54,508 WE LOOKED AT INFLAMMASOMES AND 3307 02:09:54,508 --> 02:09:56,343 EXPRESSION ACTIVATION OF 3308 02:09:56,343 --> 02:09:56,710 COAGULATION. 3309 02:09:56,710 --> 02:10:01,048 WE IS SUMMARIZE IN SAYING LPS IS 3310 02:10:01,048 --> 02:10:05,019 LEADING TO TRL4 ACTIVATION, AND 3311 02:10:05,019 --> 02:10:06,220 THEN THROUGH THE INFLAMMASOMES 3312 02:10:06,220 --> 02:10:10,357 CASPASE-11 GOING TO TISSUE 3313 02:10:10,357 --> 02:10:11,125 FACTOR EXPRESSION, THERE'S 3314 02:10:11,125 --> 02:10:13,427 INCREASED RELEASED OF EVS FROM 3315 02:10:13,427 --> 02:10:14,628 ACTIVATED MONOCYTES LEADING TO 3316 02:10:14,628 --> 02:10:15,829 ACTIVATION OF COAGULATION. 3317 02:10:15,829 --> 02:10:23,704 IN PARALLEL TO THAT PATHWAY IS 3318 02:10:23,704 --> 02:10:28,709 THE RELEASE, LEADING TO NANOPORE 3319 02:10:28,709 --> 02:10:33,881 FORMATION, CALCIUM INFLUX, 3320 02:10:33,881 --> 02:10:34,548 SERINE EXPOSURE. 3321 02:10:34,548 --> 02:10:36,283 NEXT PLEASE. 3322 02:10:36,283 --> 02:10:39,920 WE FOUND RECENTLY THAT 3323 02:10:39,920 --> 02:10:41,655 CASPASE-11 DOES NOT CONTRIBUTE 3324 02:10:41,655 --> 02:10:43,857 TO EARLIER ACTIVATION AT THREE 3325 02:10:43,857 --> 02:10:46,493 HOURS, BUT PLAYS A ROLE IN LATE 3326 02:10:46,493 --> 02:10:47,328 ACTIVATION OF COAGULATION EIGHT 3327 02:10:47,328 --> 02:10:52,700 HOURS IN THE MOUSE MODEL WITH 3328 02:10:52,700 --> 02:10:54,234 ENDOTOXEMIA. 3329 02:10:54,234 --> 02:10:55,769 NEXT PLEASE. 3330 02:10:55,769 --> 02:10:58,305 CONCLUSIONS, FIRST SEPSIS 3331 02:10:58,305 --> 02:10:59,373 ASSOCIATED COAGULOPATHY IS 3332 02:10:59,373 --> 02:11:00,607 ASSOCIATED REDUCED SURVIVAL IN 3333 02:11:00,607 --> 02:11:02,142 PATIENTS WITH SEPSIS, 3334 02:11:02,142 --> 02:11:03,444 ADMINISTRATION OF SOLUBLE 3335 02:11:03,444 --> 02:11:06,814 THROMBO MOD LYNN REDUCES 3336 02:11:06,814 --> 02:11:09,883 MORTALITY IN SEPSIS PATIENTS, 3337 02:11:09,883 --> 02:11:11,318 ASSOCIATED WITH COAGULOPATHY. 3338 02:11:11,318 --> 02:11:11,752 NEXT. 3339 02:11:11,752 --> 02:11:13,954 AND FROM A BASIC SCIENCE POINTS 3340 02:11:13,954 --> 02:11:18,425 OF VIEW, TISSUE FACTOR TRIGGERS 3341 02:11:18,425 --> 02:11:18,959 ACTIVATION COAGULATION 3342 02:11:18,959 --> 02:11:22,363 CONTRIBUTES TO DEATH IN BABOON 3343 02:11:22,363 --> 02:11:23,797 MODEL OF SEPSIS, PLAYS A MAJOR 3344 02:11:23,797 --> 02:11:26,066 ROLE IN ACTIVATION OF 3345 02:11:26,066 --> 02:11:30,471 COAGULATION IN MOUSE MODEL OF 3346 02:11:30,471 --> 02:11:31,672 ENDOTOXEMIA AND BLOCKING ON 3347 02:11:31,672 --> 02:11:33,741 MONOCYTE EXPRESSION MAY REDUCE 3348 02:11:33,741 --> 02:11:36,243 ACTIVATION OF COAGULATION OF 3349 02:11:36,243 --> 02:11:38,011 PATIENTS WITH SEPSIS WITHOUT 3350 02:11:38,011 --> 02:11:40,948 INCREASING 3351 02:11:40,948 --> 02:11:43,016 SO I'D LIKE TO ACKNOWLEDGE 3352 02:11:43,016 --> 02:11:45,419 PEOPLE THAT HAVE DONE THE WORK. 3353 02:11:45,419 --> 02:11:47,454 ANNA SAKITO HAS REALLY PIONEERED 3354 02:11:47,454 --> 02:11:49,957 ALL THE WORK THAT I PRESENTED 3355 02:11:49,957 --> 02:11:53,394 HERE TODAY, COLLABORATORS AT UNC 3356 02:11:53,394 --> 02:11:54,595 AND DIFFERENT COLLABORATORS THAT 3357 02:11:54,595 --> 02:11:56,563 I'VE PRESENTED SOME OF THAT 3358 02:11:56,563 --> 02:11:57,231 WORK. 3359 02:11:57,231 --> 02:11:59,767 PARTICULARLY THANKFUL FOR NIH 3360 02:11:59,767 --> 02:12:00,834 FUNDING TO SUPPORT THIS WORK. 3361 02:12:00,834 --> 02:12:08,642 THANK YOU FOR YOUR ATTENTION. 3362 02:12:08,642 --> 02:12:09,943 >> THANKS A LOT. 3363 02:12:09,943 --> 02:12:13,781 I THINK WE CAN MOVE TO THE NEXT 3364 02:12:13,781 --> 02:12:14,615 TALK. 3365 02:12:14,615 --> 02:12:15,716 WE CAN HAVE THE DISCUSSION AND 3366 02:12:15,716 --> 02:12:17,050 QUESTIONS AT THE END. 3367 02:12:17,050 --> 02:12:21,422 SO DO YOU WANT TO INTRODUCE? 3368 02:12:21,422 --> 02:12:25,025 >> YES, HELLO, EVERYONE. 3369 02:12:25,025 --> 02:12:28,962 I WILL INTRODUCE OUR NEXT 3370 02:12:28,962 --> 02:12:31,265 SPEAKER, PROFESSOR OF 3371 02:12:31,265 --> 02:12:33,667 PHARMACEUTICAL SCIENCES AT TEXT 3372 02:12:33,667 --> 02:12:37,171 AT A & M UNIVERSITY. 3373 02:12:37,171 --> 02:12:38,238 TALKS ABOUT DRIVERS OF 3374 02:12:38,238 --> 02:12:41,542 COAGULATION IN SEPSIS. 3375 02:12:41,542 --> 02:12:46,180 PLEASE WELCOME. 3376 02:12:46,180 --> 02:12:47,981 >> THANKS I'D LIKE TO THANK THE 3377 02:12:47,981 --> 02:12:49,082 ORGANIZERS FOR THIS OPPORTUNITY 3378 02:12:49,082 --> 02:12:53,787 AND ALSO THANK MY COLLABORATOR 3379 02:12:53,787 --> 02:12:55,856 DR. MACKMAN TO INTRODUCE OUR 3380 02:12:55,856 --> 02:13:00,027 FINDINGS. 3381 02:13:00,027 --> 02:13:04,531 THE TITLE OF MY TALK IS PYRO 3382 02:13:04,531 --> 02:13:06,066 PTOSIS DRIVES COAGULATION IN 3383 02:13:06,066 --> 02:13:08,202 SEPSIS. 3384 02:13:08,202 --> 02:13:12,372 SO I WILL USE THIS SLIDE AS 3385 02:13:12,372 --> 02:13:13,373 BACKGROUND. 3386 02:13:13,373 --> 02:13:15,642 ABOUT 10 YEARS AGO NOW, TWO IND 3387 02:13:15,642 --> 02:13:19,947 PEBT GTWOINDEPENDENT GROUPS PUBA 3388 02:13:19,947 --> 02:13:26,119 PAPER IN SCIENCE, THE MORTAL 3389 02:13:26,119 --> 02:13:28,789 MORTALITY -- WHAT THEY DID IS 3390 02:13:28,789 --> 02:13:30,123 THEY FIRST PRIMED THE MICE WITH 3391 02:13:30,123 --> 02:13:35,896 LOW DOSE LPS FOLLOWED BY -- AND 3392 02:13:35,896 --> 02:13:37,531 WHAT THEY FOUND IS IF THEY PRIME 3393 02:13:37,531 --> 02:13:44,872 THE MICE WITH LOW DOSE FIRST, 3394 02:13:44,872 --> 02:13:47,274 DEFICIENCY OF -- PROTECTED 3395 02:13:47,274 --> 02:13:49,243 AGAINST THE MORTALITY. 3396 02:13:49,243 --> 02:13:53,714 BUT IF THEY PRIME THE MICE 3397 02:13:53,714 --> 02:14:00,621 WITH -- IC -- AGONIST -- 3398 02:14:00,621 --> 02:14:03,223 DEFICIENCY OF 11 PROTECT AGAINST 3399 02:14:03,223 --> 02:14:05,626 THE MORTALITY BUT THE 3400 02:14:05,626 --> 02:14:08,061 DEFICIENCIES OF -- HAVE NO 3401 02:14:08,061 --> 02:14:08,395 EFFECT. 3402 02:14:08,395 --> 02:14:15,168 SO BASED ON THIS THEY CONCLUDED 3403 02:14:15,168 --> 02:14:16,470 THAT -- 11 DEPENDED ON -- 3404 02:14:16,470 --> 02:14:17,471 PATHWAY, HOWEVER IN THEIR 3405 02:14:17,471 --> 02:14:22,709 STUDIES, THEY DID NOT REPORT -- 3406 02:14:22,709 --> 02:14:25,445 BY WHICH THE -- 11 ACTIVATION 3407 02:14:25,445 --> 02:14:26,413 LEADED TO MORTALITY. 3408 02:14:26,413 --> 02:14:33,220 THAT'S WHAT WE WANT TO EVALUATE. 3409 02:14:33,220 --> 02:14:35,489 BRIEFLY INTRODUCE, FIRST 3410 02:14:35,489 --> 02:14:39,560 DISCOVERED 20 YEARS AGO NOW, THE 3411 02:14:39,560 --> 02:14:42,729 MAIN FUNCTION OF INFLAMMASOMES 3412 02:14:42,729 --> 02:14:46,667 IS INNATE IMMUNITY, 3413 02:14:46,667 --> 02:14:49,069 MULTI-PROTEIN OLIGOMERS 3414 02:14:49,069 --> 02:14:50,704 CONSISTING OF AT LEAST THREE 3415 02:14:50,704 --> 02:14:54,875 COMPONENTS, NLR PROTEINS, ASC 3416 02:14:54,875 --> 02:15:02,983 ADAPTER PROTEIN AND CASPASE 1. 3417 02:15:02,983 --> 02:15:04,384 ACTIVATION OF CASPASE 1 LEADING 3418 02:15:04,384 --> 02:15:10,324 TO THE PRODUCTION OF CYTOKINE 3419 02:15:10,324 --> 02:15:14,695 INTERLEUKIN 1 BETA 18 AS WELL AS 3420 02:15:14,695 --> 02:15:22,970 PYRO PTOSIS. 3421 02:15:22,970 --> 02:15:28,575 SO WE FOCUS ON GRAMS -- BACTERIA 3422 02:15:28,575 --> 02:15:34,581 THAT CAN ACTIVATE -- COMBINES 3423 02:15:34,581 --> 02:15:36,416 DIRECTLY TO CASPASE 11, LEADING 3424 02:15:36,416 --> 02:15:40,187 TO THE NON-CLINICAL ACTIVATION 3425 02:15:40,187 --> 02:15:44,958 AND BACTERIA CAN ALSO ACTIVATE 3426 02:15:44,958 --> 02:15:55,268 NLRC4 -- PROTEINS. 3427 02:16:01,975 --> 02:16:03,777 FOUND ON THE SURFACE OF 3428 02:16:03,777 --> 02:16:04,711 GRAM-NEGATIVE BACTERIA. 3429 02:16:04,711 --> 02:16:09,249 THE STRUCTURE OF -- IS LIKE A 3430 02:16:09,249 --> 02:16:10,550 SYRINGE, HAVE A LONG NEEDLE 3431 02:16:10,550 --> 02:16:12,519 PROTEIN FOLLOWED BY A LOT OF 3432 02:16:12,519 --> 02:16:13,620 PROTEIN AND A BASE. 3433 02:16:13,620 --> 02:16:15,889 WHEN BACTERIA ENCOUNTERS HOST 3434 02:16:15,889 --> 02:16:18,425 CELLS, THE NEEDLE PROTEIN CAN BE 3435 02:16:18,425 --> 02:16:20,127 INJECTED INTO THE MEMBRANE OF 3436 02:16:20,127 --> 02:16:26,199 THE HOST CELLS, AND THE PROTEIN 3437 02:16:26,199 --> 02:16:27,300 FACTORS CAN BE DELIVERED FROM 3438 02:16:27,300 --> 02:16:28,935 THIS SYSTEM FROM BACTERIA INTO 3439 02:16:28,935 --> 02:16:31,672 THE HOST CELLS, SO BACTERIA 3440 02:16:31,672 --> 02:16:35,609 USES -- TO CONTROL AND EFFECT 3441 02:16:35,609 --> 02:16:38,111 THE SIGNALING OF THE HOST CELLS. 3442 02:16:38,111 --> 02:16:40,981 IN THE LATEST, PEOPLE FOUND THAT 3443 02:16:40,981 --> 02:16:43,250 THE NEEDLE PROTEIN, STRUCTURAL 3444 02:16:43,250 --> 02:16:44,985 PROTEIN, THE NEEDLE PROTEIN 3445 02:16:44,985 --> 02:16:49,489 ESPECIALLY THE ROD PROTEIN 3446 02:16:49,489 --> 02:16:53,660 ARE -- SO WE USED EPRJ FROM THE 3447 02:16:53,660 --> 02:16:56,263 E. COLI AS A TOOL FOR 3448 02:16:56,263 --> 02:16:57,297 INVESTIGATING HOW -- ACTIVATION 3449 02:16:57,297 --> 02:17:07,841 CAN CAUSE MORTALITY IN THE HOST. 3450 02:17:09,242 --> 02:17:11,478 SO WE FIRST INJECT -- VERIFIED 3451 02:17:11,478 --> 02:17:14,915 THE -- CAN LEAD TO THE MORTALITY 3452 02:17:14,915 --> 02:17:20,687 IN THE MICE, AND -- INJECTING -- 3453 02:17:20,687 --> 02:17:23,490 POTENTLY KILLED THE MICE AND 3454 02:17:23,490 --> 02:17:30,731 THELY TTHELETHAL DOSE IS ABOU 3455 02:17:30,731 --> 02:17:31,031 3-MICROGRAM. 3456 02:17:31,031 --> 02:17:32,532 WE KNOW THAT CYTOKINE STORM IS 3457 02:17:32,532 --> 02:17:35,001 ONE OF THE MAJOR COMPLICATIONS 3458 02:17:35,001 --> 02:17:37,304 LEADING TO THE DEATH OF THE 3459 02:17:37,304 --> 02:17:37,938 SEPTIC PATIENTS. 3460 02:17:37,938 --> 02:17:42,642 SO THE FIRST -- WE FOUND A VERY 3461 02:17:42,642 --> 02:17:43,744 INTERESTING FINDINGS FOR THE 3462 02:17:43,744 --> 02:17:47,013 FIRST EXPERIMENT. 3463 02:17:47,013 --> 02:17:48,782 WE FOUND THAT SIX OUT OF EIGHT 3464 02:17:48,782 --> 02:17:54,454 MICE INJECTED WITH EPRJ, THAT -- 3465 02:17:54,454 --> 02:17:56,523 SO WE WERE REALLY EXCITED ABOUT 3466 02:17:56,523 --> 02:18:00,160 THIS FINDING BECAUSE WE KNOW 3467 02:18:00,160 --> 02:18:01,695 THAT HEMOLYSIS IS ONE OF THE 3468 02:18:01,695 --> 02:18:02,896 COMMON COMPLICATIONS OF SEPTIC 3469 02:18:02,896 --> 02:18:04,765 PATIENTS. 3470 02:18:04,765 --> 02:18:09,002 WE THOUGHT WE MIGHT DISCOVER 3471 02:18:09,002 --> 02:18:11,404 THE -- OF -- SEPSIS. 3472 02:18:11,404 --> 02:18:15,342 INITIAL HYPOTHESIS, THE PYRO 3473 02:18:15,342 --> 02:18:16,543 PTOSIS OCCURRED IN THE RED 3474 02:18:16,543 --> 02:18:17,711 CELLS, CONTRIBUTED TO THE -- 3475 02:18:17,711 --> 02:18:19,946 LEADING TO THE HOMO LYSIS, SO 3476 02:18:19,946 --> 02:18:23,116 THE NEXT DAY WE DID AN 3477 02:18:23,116 --> 02:18:24,651 INDIVIDUAL EXPERIMENT, WE 3478 02:18:24,651 --> 02:18:29,589 ISOLATED -- MICE, INCUBATED WITH 3479 02:18:29,589 --> 02:18:33,627 EPRJ, BUT WE DID NOT HIT TARGET, 3480 02:18:33,627 --> 02:18:35,595 THE PYRO PTOSIS IN THE RED 3481 02:18:35,595 --> 02:18:37,998 CELLS, BUT SIX OUT OF EIGHT MICE 3482 02:18:37,998 --> 02:18:47,507 HAD SUCH PHENOMENON, SO -- AFTER 3483 02:18:47,507 --> 02:18:49,376 WE LOOK AT THE LITERATURE, WE 3484 02:18:49,376 --> 02:18:52,712 REALIZE THAT COAGULATION WITH 3485 02:18:52,712 --> 02:18:54,614 THE -- IS ONE OF THE -- LEADING 3486 02:18:54,614 --> 02:19:00,754 TO HOME LY HEMOLYSIS IN SEPSIS. 3487 02:19:00,754 --> 02:19:04,024 SO THEN WE START TO ESTABLISH 3488 02:19:04,024 --> 02:19:05,125 ASSAYS FOR DIAGNOSIS OF 3489 02:19:05,125 --> 02:19:07,727 COAGULATION. 3490 02:19:07,727 --> 02:19:09,062 COAGULATION -- DIAGNOSED IN 3491 02:19:09,062 --> 02:19:10,497 CLINICAL -- BY A SCORING SYSTEM 3492 02:19:10,497 --> 02:19:20,207 BASED ON ASSAYS LISTED HERE. 3493 02:19:20,207 --> 02:19:21,541 PROTHROMBIN TIME IS PROLONGED 3494 02:19:21,541 --> 02:19:23,376 BECAUSE OF THE CONSUMPTION OF 3495 02:19:23,376 --> 02:19:25,478 COAGULATION FACTORS. 3496 02:19:25,478 --> 02:19:27,547 -- INCREASED DUE TO THE 3497 02:19:27,547 --> 02:19:30,717 ACTIVATION OF COAGULATION SYSTEM 3498 02:19:30,717 --> 02:19:33,119 AND -- WHERE PEOPLE CAN -- FOO 3499 02:19:33,119 --> 02:19:34,421 FIBRIN. 3500 02:19:34,421 --> 02:19:37,290 SO FIBRIN CONCENTRATIONS WERE 3501 02:19:37,290 --> 02:19:39,693 REDUCED, SEPTIC PATIENTS MOSTLY 3502 02:19:39,693 --> 02:19:43,730 HAVE THROMBOCYTOPENIA, THE COUNT 3503 02:19:43,730 --> 02:19:45,899 IS REDUCED, TISSUE FACTOR IS A 3504 02:19:45,899 --> 02:19:49,102 TRIGGER OF COAGULATION IN SEPSIS 3505 02:19:49,102 --> 02:19:58,745 AND ALSO D-DIMER IS INCREASED. 3506 02:19:58,745 --> 02:19:59,679 WE INVESTIGATED WHERE 3507 02:19:59,679 --> 02:20:02,315 COAGULATION IS ACTIVATED BY EPRJ 3508 02:20:02,315 --> 02:20:03,617 AND INDEED WE FOUND THAT 3509 02:20:03,617 --> 02:20:08,655 INJECTION OF EPRJ SIGNIFICANTLY 3510 02:20:08,655 --> 02:20:11,858 INCREASED THE PROTHROMBIN TIME 3511 02:20:11,858 --> 02:20:13,927 ALSO DECREASED THE FIBRIN 3512 02:20:13,927 --> 02:20:20,133 CONCENTRATION BY MORE THAN 50%. 3513 02:20:20,133 --> 02:20:22,435 THOSE MICE HAVE INCREASED 3514 02:20:22,435 --> 02:20:23,536 THROMBIN CONCENTRATION AND THEY 3515 02:20:23,536 --> 02:20:29,676 HAVE SEVERE THROMBOCYTOPENIA AND 3516 02:20:29,676 --> 02:20:32,512 TISSUE -- INCREASED. 3517 02:20:32,512 --> 02:20:37,117 THIS ASSAY WAS DONE BY DR. NIGEL 3518 02:20:37,117 --> 02:20:38,318 MACKMAN IN A DOUBLE BLIND 3519 02:20:38,318 --> 02:20:39,286 MANNER. 3520 02:20:39,286 --> 02:20:41,521 YES, PLEASE. 3521 02:20:41,521 --> 02:20:44,124 AND WE FURTHER INVESTIGATED 3522 02:20:44,124 --> 02:20:46,526 WHETHER THE ICs HAPPENED IN 3523 02:20:46,526 --> 02:20:51,765 THOSE MICE BY IMMUNOSTAINING AND 3524 02:20:51,765 --> 02:20:52,299 MULTIPHOTON MICROSCOPE. 3525 02:20:52,299 --> 02:20:56,036 IN THIS SLIDE WE SHOW THAT 3526 02:20:56,036 --> 02:20:57,871 FIBRIN -- IN THE MICE -- AND 3527 02:20:57,871 --> 02:21:04,010 INJECTION OF EPRJ INCREASED 3528 02:21:04,010 --> 02:21:05,645 FIBRIN -- AND THROMBOSIS. 3529 02:21:05,645 --> 02:21:08,682 WHICH WAS ABOLISHED IN THE 3530 02:21:08,682 --> 02:21:09,816 CASPASE 1 AND 11 KNOCKOUT MICE. 3531 02:21:09,816 --> 02:21:13,620 AT THAT TIME, WE ONLY HAVE THESE 3532 02:21:13,620 --> 02:21:15,388 DOUBLE KNOCKOUT MICE AVAILABLE 3533 02:21:15,388 --> 02:21:16,856 FOR INJECTION AND LATER WE USED 3534 02:21:16,856 --> 02:21:18,892 THE CASPASE 1 SINGLE KNOCKOUT 3535 02:21:18,892 --> 02:21:21,828 MICE AND VERIFIED THAT EPRJ 3536 02:21:21,828 --> 02:21:24,264 INDUCED THE IC OF FIBRIN 3537 02:21:24,264 --> 02:21:25,665 DEFINITION IS CASPASE 3538 02:21:25,665 --> 02:21:30,704 1 DEPENDENT. 3539 02:21:30,704 --> 02:21:33,974 THE COAGULATION ASSAYS, WE FOUND 3540 02:21:33,974 --> 02:21:36,643 THAT' LON GAITION OF PT TIME WAS 3541 02:21:36,643 --> 02:21:38,111 ABOLISHED IN THE CASPASE 1 AND 3542 02:21:38,111 --> 02:21:40,547 11 DOUBLE KNOCKOUT MICE AND THE 3543 02:21:40,547 --> 02:21:42,749 REDUCTION IN FIBRIN 3544 02:21:42,749 --> 02:21:44,684 CONCENTRATION IS ABOUT -- EPRJ 3545 02:21:44,684 --> 02:21:47,854 WAS ALSO ABOLISHED IN THE 3546 02:21:47,854 --> 02:21:51,257 CASPASE 1-11 KNOCKOUT MICE, TAT 3547 02:21:51,257 --> 02:21:52,459 ALSO DID NOT INCREASE IN THE 3548 02:21:52,459 --> 02:21:53,460 DOUBLE KNOCKOUT MICE. 3549 02:21:53,460 --> 02:21:55,862 BUT IN THE CASPASE 1 KNOCKOUT 3550 02:21:55,862 --> 02:21:58,365 MICE IS JUST LIKE -- MICE. 3551 02:21:58,365 --> 02:22:00,000 SO FROM THIS DATA, WE CAN 3552 02:22:00,000 --> 02:22:04,804 CONCLUDE THAT EPRJ INDUCED 3553 02:22:04,804 --> 02:22:09,209 COAGULATION MAY -- CASPASE 3554 02:22:09,209 --> 02:22:19,586 1 DEPENDENT -- SO WE USE CASP 3555 02:22:19,586 --> 02:22:23,289 CASPASE -- INDEED THE EPRJ 3556 02:22:23,289 --> 02:22:25,825 INDUCED COAGULATION WAS 3557 02:22:25,825 --> 02:22:30,964 ABOLISHED IN THE -- KNOCKOUT 3558 02:22:30,964 --> 02:22:33,600 MICE. 3559 02:22:33,600 --> 02:22:35,435 AND WE KNOW FROM DR. MACKMAN'S 3560 02:22:35,435 --> 02:22:39,072 EXHIBIT DDR. MACKMAN'S -- INTRO, 3561 02:22:39,072 --> 02:22:43,309 WE KNOW TISSUE FACTOR -- IN 3562 02:22:43,309 --> 02:22:44,511 SEPSIS, SO WHEN YOU INVESTIGATED 3563 02:22:44,511 --> 02:22:47,180 WITH EPRJ INDUCED COAGULATION, 3564 02:22:47,180 --> 02:22:48,782 REQUIRES TISSUE FACTOR, WE USE 3565 02:22:48,782 --> 02:22:51,951 THE TISSUE EFFECT TO NEUTRALIZE 3566 02:22:51,951 --> 02:22:55,588 THE ANTIBODY -- THE MICE AND 3567 02:22:55,588 --> 02:22:58,191 INJECT EPRJ INDUCED MICE AND WE 3568 02:22:58,191 --> 02:22:59,959 FOUND THAT PROLONGATION OF PT 3569 02:22:59,959 --> 02:23:05,665 TIME WAS LARGELY PREVENTED BY 3570 02:23:05,665 --> 02:23:07,700 1H1 TREATMENT AND THE -- 3571 02:23:07,700 --> 02:23:09,135 CONCENTRATION WAS ALSO REDUCED. 3572 02:23:09,135 --> 02:23:10,570 IMPORTANTLY, WE FOUND FOR 3573 02:23:10,570 --> 02:23:13,840 TREATMENT OF THE MICE WITH 3574 02:23:13,840 --> 02:23:15,508 1H1 INCREASED SURVIVAL RATE. 3575 02:23:15,508 --> 02:23:19,412 SO THIS DATA SUGGESTS THAT AT 3576 02:23:19,412 --> 02:23:22,282 LEAST THE IC IS ONE OF THE 3577 02:23:22,282 --> 02:23:25,452 MECHANISMS CONTRIBUTED TO THE 3578 02:23:25,452 --> 02:23:35,995 MORTALITY FOR -- BE ACTIVATION. 3579 02:23:36,329 --> 02:23:41,634 OTHER DATA SHOW ACTIVATION OF -- 3580 02:23:41,634 --> 02:23:45,004 PATHWAY LEAD TO -- IC. 3581 02:23:45,004 --> 02:23:47,640 SO WE USED THE LPS MODEL AND 3582 02:23:47,640 --> 02:23:53,680 FOUND INJECTION OF -- IN MICE 3583 02:23:53,680 --> 02:23:56,616 INDUCED -- MARKETLY INCREASED 3584 02:23:56,616 --> 02:24:00,420 IN -- MICE ALSO PT TIME IS 3585 02:24:00,420 --> 02:24:02,856 PROLONGED AND FIBRIN 3586 02:24:02,856 --> 02:24:04,924 CONCENTRATION IS REDUCED. 3587 02:24:04,924 --> 02:24:08,128 DEFICIENCY OF CASPASE 11 PROTECT 3588 02:24:08,128 --> 02:24:15,502 THE IC INDUCED -- BUT IN THE -- 3589 02:24:15,502 --> 02:24:18,138 MAINLY IT'S SAME AS WILD TYPE 3590 02:24:18,138 --> 02:24:18,338 MICE. 3591 02:24:18,338 --> 02:24:22,208 SO THE CONCLUSION IS LPS INDUCED 3592 02:24:22,208 --> 02:24:24,477 COAGULATION -- THROUGH THE 3593 02:24:24,477 --> 02:24:27,113 CASPASE-11 DEPENDENT MECHANISM, 3594 02:24:27,113 --> 02:24:31,618 NOT THE -- WHICH IS CONSISTENT 3595 02:24:31,618 --> 02:24:35,121 WITH THE FINDINGS OF TWO SCIENCE 3596 02:24:35,121 --> 02:24:42,095 PAPERS. 3597 02:24:42,095 --> 02:24:43,530 HOW ABOUT BACTERIA? 3598 02:24:43,530 --> 02:24:47,233 WE USE -- CONTRIBUTE TO 3599 02:24:47,233 --> 02:24:48,668 COAGULATION IN THE -- BACTERIA 3600 02:24:48,668 --> 02:24:52,939 AND A SALMONELLA IS GRAM -- 3601 02:24:52,939 --> 02:24:54,541 BACTERIA, AND FIRST WE USE THE 3602 02:24:54,541 --> 02:24:57,510 IN VITRO EXPERIMENT TO VERIFY 3603 02:24:57,510 --> 02:25:00,914 THAT SALMONELLA INDUCED THE PIE 3604 02:25:00,914 --> 02:25:08,154 RPYROPTOSIS -- MACROPHAGES AND E 3605 02:25:08,154 --> 02:25:11,524 FOUND SALMONELLA INDUCED CELL 3606 02:25:11,524 --> 02:25:15,361 DEATH MAY -- CASPASE 11 -- 3607 02:25:15,361 --> 02:25:25,538 AND -- NOT BY CASPASE 11. 3608 02:25:25,538 --> 02:25:26,639 INJECTION OF SALMONELLA INTO THE 3609 02:25:26,639 --> 02:25:30,009 MICE CAUSED COAGULATION, 3610 02:25:30,009 --> 02:25:31,778 INCREASED THE PROTHROMBIN TIME 3611 02:25:31,778 --> 02:25:35,248 AND INCREASED THROMBIN AND -- 3612 02:25:35,248 --> 02:25:35,915 CONCENTRATIONS. 3613 02:25:35,915 --> 02:25:38,351 AND COAGULATION INDUCED BY 3614 02:25:38,351 --> 02:25:41,120 SALMONELLA IS LARGELY PREVENTED 3615 02:25:41,120 --> 02:25:46,626 BY CASPASE 1 DEFICIENCY SHOWN IN 3616 02:25:46,626 --> 02:25:49,929 GREEN AND THE -- SHOWN IN BLUE. 3617 02:25:49,929 --> 02:25:52,665 AND TO A LESSER EXTENT, 3618 02:25:52,665 --> 02:25:57,136 DEFICIENCY OF PA CASPASE 11 OR E 3619 02:25:57,136 --> 02:25:59,973 NAIP WHICH IS A RECEPTOR OF 3620 02:25:59,973 --> 02:26:03,710 THE -- FOR THE -- AND -- 3621 02:26:03,710 --> 02:26:05,778 PROTEINS ALSO INHIBITED THE 3622 02:26:05,778 --> 02:26:15,989 COAGULATION. 3623 02:26:16,356 --> 02:26:18,458 SO THE CONCLUSION OF FINDINGS OF 3624 02:26:18,458 --> 02:26:20,994 ACTIVATION OF BOTH -- AND 3625 02:26:20,994 --> 02:26:27,000 NON- -- COMB S CHROMOSOME LEADI- 3626 02:26:27,000 --> 02:26:28,668 OF THE MACROPHAGES AND RELEASED 3627 02:26:28,668 --> 02:26:33,673 MICRO PARTICLES FROM THIS PYRO 3628 02:26:33,673 --> 02:26:36,075 PTOTIC CELLS -- LEADING TO DEATH 3629 02:26:36,075 --> 02:26:40,747 OF THE HOST. 3630 02:26:40,747 --> 02:26:44,784 I'D LIKE TO THANK MY 3631 02:26:44,784 --> 02:26:50,390 COLLABORATORS AND ALSO 3632 02:26:50,390 --> 02:26:52,225 DR. MACKMAN AND THIS WORK WAS 3633 02:26:52,225 --> 02:26:59,999 MAINLY DONE BY MY POSTDOC, 3634 02:26:59,999 --> 02:27:03,436 DR. WU, WHO GOT THE K-9 # 9 -- 3635 02:27:03,436 --> 02:27:05,805 GRANTED BY THE FACULTY POSITION 3636 02:27:05,805 --> 02:27:08,841 AT THE UNIVERSITY AND ALSO THANK 3637 02:27:08,841 --> 02:27:10,943 YOU FOR THE FUNDING FROM NIH FOR 3638 02:27:10,943 --> 02:27:11,177 SUPPORT. 3639 02:27:11,177 --> 02:27:15,315 THANK YOU FOR YOUR ATTENTION. 3640 02:27:15,315 --> 02:27:17,050 >> THANK YOU VERY MUCH, DR. LI, 3641 02:27:17,050 --> 02:27:18,384 FOR A GREAT PRESENTATION. 3642 02:27:18,384 --> 02:27:21,054 WE WILL HAVE A Q & A SESSION AT 3643 02:27:21,054 --> 02:27:23,189 THE END OF THE LAST SPEAKER'S 3644 02:27:23,189 --> 02:27:23,856 PRESENTATION. 3645 02:27:23,856 --> 02:27:25,258 SO PLEASE FEEL FREE TO LEAVE 3646 02:27:25,258 --> 02:27:27,794 YOUR QUESTIONS IN THE CHAT BOX. 3647 02:27:27,794 --> 02:27:29,962 SO I THINK NOW WE MAY MOVE ON TO 3648 02:27:29,962 --> 02:27:34,667 OUR NEXT SPEAKER, DR. KANDACE 3649 02:27:34,667 --> 02:27:36,436 GOLLOMP, ASSISTANT PROFESSOR OF 3650 02:27:36,436 --> 02:27:38,771 PEDIATRIC HEMATOLOGY AT 3651 02:27:38,771 --> 02:27:41,908 CHILDREN'S HOSPITAL OF 3652 02:27:41,908 --> 02:27:44,010 PHILADELPHIA. 3653 02:27:44,010 --> 02:27:48,014 DR. GOLLOMP WILL TALK ABOUT 3654 02:27:48,014 --> 02:27:50,316 NEUTROPHIL EXTRACELLULAR TRAPS, 3655 02:27:50,316 --> 02:27:52,318 PLATELET FACTOR 4 AND BACK TIER 3656 02:27:52,318 --> 02:27:53,920 YOUR INFORECAST: A CHARGED 3657 02:27:53,920 --> 02:27:54,187 SUBJECT. 3658 02:27:54,187 --> 02:27:54,520 THANK YOU. 3659 02:27:54,520 --> 02:27:55,788 >> THANK YOU SO MUCH FOR THAT 3660 02:27:55,788 --> 02:27:56,556 WARM INTRODUCTION AND I WANT TO 3661 02:27:56,556 --> 02:27:58,825 THANK THE ORGANIZERS AND 3662 02:27:58,825 --> 02:28:00,259 PARTICULARLY DR. SUND FOR THE 3663 02:28:00,259 --> 02:28:01,027 OPPORTUNITY TO PRESENT SOME OF 3664 02:28:01,027 --> 02:28:03,763 THIS WORK. 3665 02:28:03,763 --> 02:28:05,064 SO I'LL BEGIN THE PRESENTATION 3666 02:28:05,064 --> 02:28:07,600 BY TALKING ABOUT NEUTROPHILS. 3667 02:28:07,600 --> 02:28:09,001 THEY'RE THE PREDOMINANT 3668 02:28:09,001 --> 02:28:11,204 CIRCULATING WHITE BLOOD CELLS IN 3669 02:28:11,204 --> 02:28:12,171 HUMANS AND WE THINK ABOUT THEM 3670 02:28:12,171 --> 02:28:13,940 AS THE FIRST CELLS TO ARRIVE AT 3671 02:28:13,940 --> 02:28:16,008 SITES OF INFECTION, INFLAMMATION 3672 02:28:16,008 --> 02:28:17,777 OR VASCULAR DAMAGE. 3673 02:28:17,777 --> 02:28:19,178 WHEN THEY GET THERE, THEY CAN 3674 02:28:19,178 --> 02:28:24,217 MEET BACTERIA. 3675 02:28:24,217 --> 02:28:25,852 , BACTERIAL TOXINS, THEY CAN 3676 02:28:25,852 --> 02:28:27,387 MEET INFLAMMATORY CYTOKINES AND 3677 02:28:27,387 --> 02:28:29,155 ALSO MEET DAMAGE ASSOCIATED 3678 02:28:29,155 --> 02:28:30,123 MOLECULAR PROTEINS, ONE THAT I 3679 02:28:30,123 --> 02:28:33,860 THINK ABOUT A LOT IS HEME, AND 3680 02:28:33,860 --> 02:28:34,961 ALL OF THESE CAN THROUGH 3681 02:28:34,961 --> 02:28:37,363 DIFFERENT PATHWAYS INTRODUCE 3682 02:28:37,363 --> 02:28:39,665 NEUTROPHILS TO RELEASE 3683 02:28:39,665 --> 02:28:42,034 NEUTROPHIL EVER BEEN EXT 3684 02:28:42,034 --> 02:28:42,502 EXTRACELLULAR TRAPS. 3685 02:28:42,502 --> 02:28:44,704 THIS IS HOW YOU SEE THEM ON THE 3686 02:28:44,704 --> 02:28:45,104 PERIPHERAL SMEAR. 3687 02:28:45,104 --> 02:28:48,808 SO NET ARE COMB TIN THAT'S BEEN 3688 02:28:48,808 --> 02:28:50,042 EXTRUDED INTO THE EXTRACELLULAR 3689 02:28:50,042 --> 02:28:50,710 SPACE. 3690 02:28:50,710 --> 02:28:52,545 THEY'RE COMPOSED OF CELL-FREE 3691 02:28:52,545 --> 02:28:53,780 DNA MIXED WITH HISTONES AS WELL 3692 02:28:53,780 --> 02:28:56,716 AS NEUTROPHIL ANTIMICROBIAL 3693 02:28:56,716 --> 02:28:57,383 PROTEINS. 3694 02:28:57,383 --> 02:28:58,785 ON ONE HAND THAT'S REALLY GOOD 3695 02:28:58,785 --> 02:29:00,520 AT HELPING TO CAPTURE AND 3696 02:29:00,520 --> 02:29:01,521 POTENTIALLY KILL CERTAIN 3697 02:29:01,521 --> 02:29:02,488 BACTERIA, BUT YOU CAN IMAGINE 3698 02:29:02,488 --> 02:29:04,056 ALL OF THOSE THINGS IN THE NETS 3699 02:29:04,056 --> 02:29:06,559 SUCH AS THE CELL-FREE DNA, THE 3700 02:29:06,559 --> 02:29:08,194 HISTONES, THE ANTIMICROBIAL 3701 02:29:08,194 --> 02:29:10,163 PROTEINS WHEN RELEASED IN A 3702 02:29:10,163 --> 02:29:11,230 DYSREGULATED MANNER CAN CAUSE 3703 02:29:11,230 --> 02:29:16,068 HARM TO THE HOST AND JUST AS DRS 3704 02:29:16,068 --> 02:29:21,541 CAN CONTRIBUTE TO THROMBOSIS. 3705 02:29:21,541 --> 02:29:23,042 I DO WANT TO HIGHLIGHT A PROTEIN 3706 02:29:23,042 --> 02:29:24,177 THAT IS VERY IMPORTANT TO NET 3707 02:29:24,177 --> 02:29:29,081 RELEASE IS SOMETHING CALLED -- 3708 02:29:29,081 --> 02:29:30,516 4, IT TRANS LOCATES TO THE 3709 02:29:30,516 --> 02:29:31,717 NUCLEUS WHERE IT MODIFIES 3710 02:29:31,717 --> 02:29:32,919 HISTONES TO DECREASE THEIR 3711 02:29:32,919 --> 02:29:35,655 OVERALL POSITIVE CHARGE, THEREBY 3712 02:29:35,655 --> 02:29:36,956 DECREASING THEIR AFFINITY FOR 3713 02:29:36,956 --> 02:29:39,258 NEGATIVELY CHARGED DNA AND THIS 3714 02:29:39,258 --> 02:29:41,327 POTENTIATES CHROMATIN D 3715 02:29:41,327 --> 02:29:44,163 CONDENSATION. 3716 02:29:44,163 --> 02:29:45,932 SO BECAUSE NETS CAN CAUSE 3717 02:29:45,932 --> 02:29:47,033 COLLATERAL HOST TISSUE INJURY 3718 02:29:47,033 --> 02:29:48,668 THAT RESULTS IN ORGAN 3719 02:29:48,668 --> 02:29:50,303 DYSFUNCTION AND MORTALITY IN 3720 02:29:50,303 --> 02:29:53,906 SEPSIS, THERE'S REAL INTEREST IN 3721 02:29:53,906 --> 02:29:56,742 DEVELOPING THERAPEUTICS THAT CAN 3722 02:29:56,742 --> 02:29:57,076 TARGET NETS. 3723 02:29:57,076 --> 02:29:59,912 THESE ARE FOUR CATEGORIES OF 3724 02:29:59,912 --> 02:30:00,246 THERAPEUTICS. 3725 02:30:00,246 --> 02:30:02,114 THIS IS PRIMARILY DONE WITH 3726 02:30:02,114 --> 02:30:02,448 NUCLEASES. 3727 02:30:02,448 --> 02:30:04,851 CAN YOU NEUTRALIZE THE TOXICITY 3728 02:30:04,851 --> 02:30:06,953 OF NET COMPONENTS, FOR EXAMPLE 3729 02:30:06,953 --> 02:30:08,988 LIKE DR. MACKMAN MENTIONED, CAN 3730 02:30:08,988 --> 02:30:11,858 YOU USE SOLUBLE -- TO NEWT LICE 3731 02:30:11,858 --> 02:30:12,358 HISTONES. 3732 02:30:12,358 --> 02:30:14,160 THERE'S ALSO THE DEVELOPMENT OF 3733 02:30:14,160 --> 02:30:15,361 CELL-FREE DNA SCAVENGERS THAT 3734 02:30:15,361 --> 02:30:17,296 CAN REDUCE THE INFLAMMATORY 3735 02:30:17,296 --> 02:30:18,731 POTENTIAL OF NETS. 3736 02:30:18,731 --> 02:30:20,066 BUT I'M GOING TO FOCUS THE REST 3737 02:30:20,066 --> 02:30:21,667 OF THE TALK ON THE LAST TWO. 3738 02:30:21,667 --> 02:30:23,102 ONE IS CAN YOU MODIFY A NET TO 3739 02:30:23,102 --> 02:30:25,304 MAKE IT LESS TOXIC BUT DO ITS 3740 02:30:25,304 --> 02:30:26,506 JOB BETTER, AND THEN WHAT 3741 02:30:26,506 --> 02:30:28,241 HAPPENS TO THE INFLAMMATORY 3742 02:30:28,241 --> 02:30:29,775 MILIEU WHEN YOU INHIBIT THE 3743 02:30:29,775 --> 02:30:30,543 RELEASE OF NETS. 3744 02:30:30,543 --> 02:30:32,512 SO WE'LL START BY TALKING ABOUT 3745 02:30:32,512 --> 02:30:40,286 NET MODIFICATION. 3746 02:30:40,286 --> 02:30:41,287 THE NET IS IN GREEN. 3747 02:30:41,287 --> 02:30:46,626 WE CAN PLAY THE VIDEO. 3748 02:30:46,626 --> 02:30:49,228 THIS IS BEING INFUSED WITH 3749 02:30:49,228 --> 02:30:50,329 PLATELET RICH PLASMA. 3750 02:30:50,329 --> 02:30:51,864 WHAT I WANT TO HIGHLIGHT IS JUST 3751 02:30:51,864 --> 02:30:53,299 HOW GREAT THESE NETS ARE AT 3752 02:30:53,299 --> 02:30:58,771 COMPANY TOURIN --AT CAPTURING T. 3753 02:30:58,771 --> 02:31:00,673 IT BECOMES A LITTLE CONDENSED AS 3754 02:31:00,673 --> 02:31:02,375 THOSE PLATELETS ARE INFUSED IN. 3755 02:31:02,375 --> 02:31:03,576 ONE OF THE REASONS I THINK THAT 3756 02:31:03,576 --> 02:31:04,911 HAPPENS IS THAT THESE PLATELETS 3757 02:31:04,911 --> 02:31:06,646 ARE CAPTURED, THEY REDUCE THE 3758 02:31:06,646 --> 02:31:16,289 CONTENTS OF THEIR GRANULES. 3759 02:31:16,289 --> 02:31:17,924 ONE OF THE MAJOR COMPONENTS OF 3760 02:31:17,924 --> 02:31:20,226 PLAY LET ALPHA GRANULES IS A 3761 02:31:20,226 --> 02:31:22,094 PLATELET SPECIFIC HEMOKINE 3762 02:31:22,094 --> 02:31:25,565 CALLED PLATELET FACTOR 4 THAT 3763 02:31:25,565 --> 02:31:32,138 FORMS AT THE T TETROMERS. 3764 02:31:32,138 --> 02:31:33,639 YOU CAN SEE THIS ILLUSTRATED IN 3765 02:31:33,639 --> 02:31:34,206 ORANGE AND RED. 3766 02:31:34,206 --> 02:31:35,875 BECAUSE OF THIS POSITIVE CHARGE, 3767 02:31:35,875 --> 02:31:38,244 IT LOVES TO BIND TO POLYANIONS, 3768 02:31:38,244 --> 02:31:41,113 SO IT CAN COMBINE TO HEPARAN, WE 3769 02:31:41,113 --> 02:31:44,817 CAN THINK OF THAT AS -- IT CAN 3770 02:31:44,817 --> 02:31:46,352 ALSO CORRESPOND TO NEGATIVELY 3771 02:31:46,352 --> 02:31:51,390 CHARGED DNA, A N A MAJOR CONSTIT 3772 02:31:51,390 --> 02:31:54,360 OF NETS AND IT CAN ALSO COMBINE 3773 02:31:54,360 --> 02:31:55,294 ON THE SURFACE OF BACTERIA. 3774 02:31:55,294 --> 02:31:58,698 IF YOU'RE A GRAM POSITIVE 3775 02:31:58,698 --> 02:31:59,732 BACTERIA, THAT'S VERY NEGATIVELY 3776 02:31:59,732 --> 02:32:00,132 CHARGED. 3777 02:32:00,132 --> 02:32:04,503 IF YOU'RE A GRAM GRAM-NEGATIVE 3778 02:32:04,503 --> 02:32:07,640 ORGANISM, IT GOING TO BE -- WILL 3779 02:32:07,640 --> 02:32:09,108 FORM COMPLEXES WITH PLATELET 3780 02:32:09,108 --> 02:32:14,113 FACTOR 4. 3781 02:32:14,113 --> 02:32:15,448 SO TO INVESTIGATE INTERACTIONS 3782 02:32:15,448 --> 02:32:18,284 BETWEEN PLATELET FACTOR 4 AND 3783 02:32:18,284 --> 02:32:19,919 NETS, I DEVELOPED A MICRO FLEW 3784 02:32:19,919 --> 02:32:21,153 DICK ASSAY. 3785 02:32:21,153 --> 02:32:22,788 IN THIS ASSAY, YOU TAKE 3786 02:32:22,788 --> 02:32:24,423 NEUTROPHILS FROM A HEALTHY HUMAN 3787 02:32:24,423 --> 02:32:27,026 DONOR AND IMMOBILIZE THEM ON 3788 02:32:27,026 --> 02:32:28,995 FIBRIN ENACTED CHANNELS AFTER 3789 02:32:28,995 --> 02:32:30,529 WHICH YOU CAN ACTIVATE THEM TO 3790 02:32:30,529 --> 02:32:31,397 RELEASE NETS. 3791 02:32:31,397 --> 02:32:35,635 HERE YOU CAN SEE ON THE TOP 3792 02:32:35,635 --> 02:32:37,403 THERE ARE NETS THAT WERE JUST 3793 02:32:37,403 --> 02:32:38,604 INCUBATED WITH BUFFER ALONE AND 3794 02:32:38,604 --> 02:32:40,239 BEFORE THEY GOT DIGESTED, THEY 3795 02:32:40,239 --> 02:32:42,108 HAVE A FLUFFY CLOUD-LIKE 3796 02:32:42,108 --> 02:32:42,642 APPEARANCE. 3797 02:32:42,642 --> 02:32:43,876 BUT THE NETS ON THE BOTTOM 3798 02:32:43,876 --> 02:32:45,811 CHANNEL WHICH WERE INCUBATED 3799 02:32:45,811 --> 02:32:48,681 WITH PF4 TAKE ON THIS SORT OF 3800 02:32:48,681 --> 02:32:50,549 FILAMENTOUS APPEARANCE BECAUSE 3801 02:32:50,549 --> 02:32:51,183 PF4 WILL TETHER TOGETHER THE 3802 02:32:51,183 --> 02:32:52,184 DIFFERENT STRANDS OF DNA AND 3803 02:32:52,184 --> 02:32:53,486 MAKE THE NETS BECOME COMPACT. 3804 02:32:53,486 --> 02:32:55,721 BUT THAT CHANGE IN MORPHOLOGY, 3805 02:32:55,721 --> 02:32:57,323 THAT COMPACTION, ALSO GOES ALONG 3806 02:32:57,323 --> 02:32:58,658 WITH AN ACQUISITION OF 3807 02:32:58,658 --> 02:33:01,927 RESISTANCE TO NUCLEASE 3808 02:33:01,927 --> 02:33:02,695 DIGESTION. 3809 02:33:02,695 --> 02:33:06,098 THIS HOLDS THROUGH TO 3810 02:33:06,098 --> 02:33:06,966 NNASE1 THAT IS PRESENT IN THE 3811 02:33:06,966 --> 02:33:08,501 CIRCULATION AND CONSTANTLY 3812 02:33:08,501 --> 02:33:09,869 SLOWLY DIGESTING NETS AND THIS 3813 02:33:09,869 --> 02:33:11,971 IS ALSO TRUE FOR BACTERIAL 3814 02:33:11,971 --> 02:33:13,072 DERIVED NUCLEASES THAT CAN BREAK 3815 02:33:13,072 --> 02:33:16,676 DOWN NETS. 3816 02:33:16,676 --> 02:33:18,878 WHAT DOES THIS MEAN IN TERMS OF 3817 02:33:18,878 --> 02:33:19,512 ENDOTHELIAL TOXICITY? 3818 02:33:19,512 --> 02:33:21,480 SO IF YOU INCUBATE UNMODIFIED 3819 02:33:21,480 --> 02:33:25,551 NETS WITH ENDOTHELIUM AS 3820 02:33:25,551 --> 02:33:27,186 INDICATED IN THE IMAGE ON TOP 3821 02:33:27,186 --> 02:33:28,587 IT'S QUITE TOXIC TO THE END TEAL 3822 02:33:28,587 --> 02:33:30,623 YUM AND WILL CAUSE EC CELL DEATH 3823 02:33:30,623 --> 02:33:31,557 AND DETACHMENT FROM THE 3824 02:33:31,557 --> 02:33:32,758 CHANNELS. 3825 02:33:32,758 --> 02:33:35,261 HOWEVER, IF YOU ADD IN PLATELET 3826 02:33:35,261 --> 02:33:36,462 FACTOR 4 TO THOSE NETS AND YOU 3827 02:33:36,462 --> 02:33:37,797 COMPACT THEM, IT CAUSES 3828 02:33:37,797 --> 02:33:39,665 PROTECTION TO THE ENDOTHELIAL 3829 02:33:39,665 --> 02:33:41,500 CELLS AND THESE ENDOTHELIAL 3830 02:33:41,500 --> 02:33:43,469 CELLS REMAIN INTACT AND MAINTAIN 3831 02:33:43,469 --> 02:33:45,438 THEIR CONFLUENCE. 3832 02:33:45,438 --> 02:33:47,073 FOR THE SAKE OF TIME WE'LL JUST 3833 02:33:47,073 --> 02:33:49,608 SWITCH TO THE NEXT SLIDE. 3834 02:33:49,608 --> 02:33:52,611 NOW WHAT DOES THIS CHANGE IN NET 3835 02:33:52,611 --> 02:33:53,746 MORPHOLOGY HAVE TO DO WITH 3836 02:33:53,746 --> 02:33:54,380 BACTERIAL KILLING? 3837 02:33:54,380 --> 02:33:55,815 DOES IT INFLUENCE THE ABILITY OF 3838 02:33:55,815 --> 02:34:00,419 NETS TO DO THEIR JOB? 3839 02:34:00,419 --> 02:34:03,823 TO ANSWER THAT, WE WENT BACK TO 3840 02:34:03,823 --> 02:34:05,458 THESE MICRO FLUIDIC CHANNELS. 3841 02:34:05,458 --> 02:34:07,426 WE HAVE BACTERIA NOW LABELED IN 3842 02:34:07,426 --> 02:34:07,960 GREEN. 3843 02:34:07,960 --> 02:34:09,061 WHAT YOU'LL NOTICE IS THAT WHEN 3844 02:34:09,061 --> 02:34:10,429 WE INFUSE IN THAT BACTERIA TO 3845 02:34:10,429 --> 02:34:11,797 THE TOP CHANNEL THAT'S JUST BEEN 3846 02:34:11,797 --> 02:34:13,566 INCUBATED WITH BUFFER ALONE, THE 3847 02:34:13,566 --> 02:34:14,867 NETS THEMSELVES DO QUITE A POOR 3848 02:34:14,867 --> 02:34:16,936 JOB OF CAPTURING BACTERIA, AND I 3849 02:34:16,936 --> 02:34:19,138 THINK THIS IS A CHARGE-MEDIATED 3850 02:34:19,138 --> 02:34:20,439 PHENOMENON WHERE THE DNA OF THE 3851 02:34:20,439 --> 02:34:23,075 NET IS REPELLING THE 3852 02:34:23,075 --> 02:34:24,176 PREDOMINANTLY NEGATIVELY CHARGED 3853 02:34:24,176 --> 02:34:24,610 BACTERIA. 3854 02:34:24,610 --> 02:34:26,512 HOWEVER, WHEN YOU'VE COMPACTED 3855 02:34:26,512 --> 02:34:28,514 YOUR NETS WITH PF4, YOU HAVE 3856 02:34:28,514 --> 02:34:29,949 THIS CAT IONIC GLUE BETWEEN THAT 3857 02:34:29,949 --> 02:34:31,617 DNA BACKBONE AND THE NEGATIVELY 3858 02:34:31,617 --> 02:34:33,452 CHARGED BUG AND IT ACTUALLY 3859 02:34:33,452 --> 02:34:35,654 HELPS TO TETHER THE BUGS TO THE 3860 02:34:35,654 --> 02:34:37,723 NETS. 3861 02:34:37,723 --> 02:34:39,458 NOW THIS IS ALSO RELEVANT 3862 02:34:39,458 --> 02:34:42,094 BECAUSE OUR PF4 COMPACTED NETS 3863 02:34:42,094 --> 02:34:43,629 ARE RESIST TABT TO NUCLEASE 3864 02:34:43,629 --> 02:34:45,798 DIGESTION, SO WHILE NAKED NETS 3865 02:34:45,798 --> 02:34:49,001 ARE RAPIDLY INGESTED WHEN WE -- 3866 02:34:49,001 --> 02:34:51,170 RELEASING A LARGE BOLUS OF 3867 02:34:51,170 --> 02:34:52,171 BACTERIA, THESE DO A MUCH BETTER 3868 02:34:52,171 --> 02:34:54,373 JOB OF RETAINING THE BACTERIA. 3869 02:34:54,373 --> 02:34:56,008 THIS CAN BE BOTH HELPFUL IF YOUR 3870 02:34:56,008 --> 02:34:57,910 NETS ARE EXPOSED TO NUCLEASES 3871 02:34:57,910 --> 02:35:00,045 THAT ARE ENDOGENOUSLY PRODUCED 3872 02:35:00,045 --> 02:35:02,014 OR IF THE BACTERIA IS MAKING 3873 02:35:02,014 --> 02:35:03,549 NUCLEASE TO EVADE NET, THIS 3874 02:35:03,549 --> 02:35:04,550 STRATEGY COULD HELP TO OVERCOME 3875 02:35:04,550 --> 02:35:09,555 THAT. 3876 02:35:09,555 --> 02:35:11,557 WHAT DOES THIS MEAN IN VIVO? 3877 02:35:11,557 --> 02:35:16,996 WE MODIFIED THE SURREY MODEL OF 3878 02:35:16,996 --> 02:35:17,530 SEPSIS. 3879 02:35:17,530 --> 02:35:20,699 WHEN YOU HARVEST THE CECAL 3880 02:35:20,699 --> 02:35:22,768 CONTENTS AND I JECT IT INTO A 3881 02:35:22,768 --> 02:35:25,204 MANUAL TO INDUCE POLYMICROBIAL 3882 02:35:25,204 --> 02:35:25,638 SEPSIS. 3883 02:35:25,638 --> 02:35:26,739 WE MODIFIED IT A LITTLE BIT 3884 02:35:26,739 --> 02:35:29,175 BECAUSE WE TOOK OUR DONOR CS 3885 02:35:29,175 --> 02:35:30,910 INKNOCK LUM AND MIXED IT WITH 3886 02:35:30,910 --> 02:35:32,745 JUST DEXTROSE ALONE OR IN BLUE 3887 02:35:32,745 --> 02:35:37,483 WE COMBINED IT WITH PF4 AND THEN 3888 02:35:37,483 --> 02:35:38,584 SUBSEQUENTLY INJECTED INTO 3889 02:35:38,584 --> 02:35:42,721 ANIMALS TO IB DUES BA BACTEREMI. 3890 02:35:42,721 --> 02:35:44,890 WHEN WE COLLECTED BLOOD, SPLEEN 3891 02:35:44,890 --> 02:35:46,792 AND LIVER AT 24 HOURS WHAT WE 3892 02:35:46,792 --> 02:35:48,227 TOABED IS THAT IS THAT PLATELET 3893 02:35:48,227 --> 02:35:49,428 FACTOR 4 TREATMENT LED TO 3894 02:35:49,428 --> 02:35:50,996 REDUCTION IN BACTEREMIA AS WELL 3895 02:35:50,996 --> 02:35:52,798 AS A REDUCTION IN THE BACTERIAL 3896 02:35:52,798 --> 02:35:54,333 LOAD THAT WE WERE ABLE TO 3897 02:35:54,333 --> 02:35:57,837 APPRECIATE IN THE LIVER AND THE 3898 02:35:57,837 --> 02:35:59,905 SPLEEN. 3899 02:35:59,905 --> 02:36:01,340 THEN WHEN WE WENT TO LOOK AT 3900 02:36:01,340 --> 02:36:02,641 SURVIVAL WHAT WE FOUND USING 3901 02:36:02,641 --> 02:36:03,943 THIS MODEL IS THAT THERE WAS A 3902 02:36:03,943 --> 02:36:05,444 RAPID DEMISE OF THE WILD TYPE 3903 02:36:05,444 --> 02:36:07,479 ANIMALS THAT WERE TREATED WITH 3904 02:36:07,479 --> 02:36:08,647 CECAL SLURRY ALONE, HOWEVER, 3905 02:36:08,647 --> 02:36:10,416 WHEN THAT CECAL SLURRY WAS 3906 02:36:10,416 --> 02:36:11,951 COMBINED WITH PLATELET FACTOR 4, 3907 02:36:11,951 --> 02:36:13,819 WE HAD 100% SURVIVAL IN THIS 3908 02:36:13,819 --> 02:36:15,020 SMALL UNPUBLISHED COHORT AND 3909 02:36:15,020 --> 02:36:18,824 WHEN WE LOOKED AT PF4 DEFICIENT 3910 02:36:18,824 --> 02:36:20,125 ANIMALS THERE WAS A SLIGHTLY 3911 02:36:20,125 --> 02:36:22,294 MORE RAPID DEMISE BUT WHEN WE 3912 02:36:22,294 --> 02:36:24,830 TREATED THOSE ANIMALS WITH 3913 02:36:24,830 --> 02:36:26,165 EXOGENOUS PLATELET FACTOR 4 WE 3914 02:36:26,165 --> 02:36:28,267 WERE ABLE TO RESCUE SURVIVAL, 3915 02:36:28,267 --> 02:36:31,203 NOT QUITE TO THE SAME LEVEL AS 3916 02:36:31,203 --> 02:36:32,404 PF4 EXPRESSING ANIMALS BUT WE 3917 02:36:32,404 --> 02:36:34,139 WERE ABLE TO GET CLOSER. 3918 02:36:34,139 --> 02:36:36,108 SO MOVING ON A LITTLE BIT FROM 3919 02:36:36,108 --> 02:36:38,944 NET MODIFICATION TO NET 3920 02:36:38,944 --> 02:36:41,380 INHIBITION. 3921 02:36:41,380 --> 02:36:44,984 SO I'M INTERESTED IN WHAT 3922 02:36:44,984 --> 02:36:47,152 LOCKING MU PTOSIS MIGHT MEAN -- 3923 02:36:47,152 --> 02:36:48,153 THERE'S A BIT OF A CONTROVERSY 3924 02:36:48,153 --> 02:36:50,322 ABOUT THIS BECAUSE ON ONE 3925 02:36:50,322 --> 02:36:51,857 HANDSOME PEOPLE ARGUE NET DO 3926 02:36:51,857 --> 02:36:53,492 MORE HARM THAN GOOD, GET RID OF 3927 02:36:53,492 --> 02:36:56,562 THEM, BLOCK THEM, BUT IT'S A 3928 02:36:56,562 --> 02:36:57,329 RELATIVELY CONSERVED FUNCTION 3929 02:36:57,329 --> 02:37:00,065 AND IT POSSIBLE THAT BLOCKING 3930 02:37:00,065 --> 02:37:02,034 MIGHT INCREASE SUSCEPTIBILITY TO 3931 02:37:02,034 --> 02:37:08,274 BACTERIAL INFECTION. 3932 02:37:08,274 --> 02:37:12,011 STOSO OTHER PEOPLE HAVE GOTTEN N 3933 02:37:12,011 --> 02:37:14,413 WELL WILL HAVE ME, THEY 3934 02:37:14,413 --> 02:37:16,348 DEVELOPED A PAD 4 DEFICIENT 3935 02:37:16,348 --> 02:37:18,450 MOUSE, AN ESSENTIAL MEDIATOR OF 3936 02:37:18,450 --> 02:37:18,884 NET RELEASE. 3937 02:37:18,884 --> 02:37:20,185 SINCE THAT TIME, IT BEEN 3938 02:37:20,185 --> 02:37:22,288 DISCOVERED THAT THERE ARE PAD 3939 02:37:22,288 --> 02:37:23,455 4 INDEPENDENT WAYS THAT YOU CAN 3940 02:37:23,455 --> 02:37:27,626 GO ABOUT JEB RATI GENERATING A T 3941 02:37:27,626 --> 02:37:29,161 HOWEVER PAD DEFICIENCY DOES LEAD 3942 02:37:29,161 --> 02:37:34,733 TO A MARKED DEFECT. 3943 02:37:34,733 --> 02:37:36,168 THESE MICE HAVE BEEN USED IN A 3944 02:37:36,168 --> 02:37:37,569 HOST OF STUDIES IN THE SETTING 3945 02:37:37,569 --> 02:37:38,671 OF DIFFERENT INFECTIOUS 3946 02:37:38,671 --> 02:37:38,938 DISEASES. 3947 02:37:38,938 --> 02:37:42,775 IN THIS STUDY LED BY DR. BARONE 3948 02:37:42,775 --> 02:37:44,476 ET AL. AT BROWN UNIVERSITY BACK 3949 02:37:44,476 --> 02:37:46,445 IN 2018, INTERESTINGLY THEY USED 3950 02:37:46,445 --> 02:37:48,647 THE CLP MODEL OF SEPSIS IN WHICH 3951 02:37:48,647 --> 02:37:51,383 THE CECUM IS PERFORATED AND THEN 3952 02:37:51,383 --> 02:37:53,886 GI MICROBIOTA GO ON TO INDUCE 3953 02:37:53,886 --> 02:37:54,987 POLYMICROBIAL SEPSIS TO 3954 02:37:54,987 --> 02:37:56,522 ILLUSTRATE THAT THERE WAS A 3955 02:37:56,522 --> 02:37:58,891 PROTECTION IN PAD4 NET DEFICIENT 3956 02:37:58,891 --> 02:38:01,660 ANIMALS FROM MORTALITY AND THEIR 3957 02:38:01,660 --> 02:38:05,497 POLYMICROBIAL SEPSIS MODEL. 3958 02:38:05,497 --> 02:38:06,699 THAT'S JUST ILLUSTRATED WITH 3959 02:38:06,699 --> 02:38:09,368 THIS SURVIVAL CURVE. 3960 02:38:09,368 --> 02:38:12,037 I WANTED TO SEE IF WE COULD 3961 02:38:12,037 --> 02:38:13,339 RECAPITULATE THESE FIND NGS OUR 3962 02:38:13,339 --> 02:38:15,074 CECAL SLURRY MODEL OF SEPSIS. 3963 02:38:15,074 --> 02:38:17,042 AND SO TO TRY TO BE AS CLOSE TO 3964 02:38:17,042 --> 02:38:19,144 THE CLP MODEL IN WHICH ALL 3965 02:38:19,144 --> 02:38:21,113 ANIMALS BECOME SEPTIC WITH THEIR 3966 02:38:21,113 --> 02:38:23,315 OWN ENDOGENOUS G.I. MICROBES, 3967 02:38:23,315 --> 02:38:25,250 WHAT WE DID IS WE HARVESTED 3968 02:38:25,250 --> 02:38:28,420 CECAL CONTENTS FROM PAD4 OR WILD 3969 02:38:28,420 --> 02:38:29,955 TYPE DONOR MICE AND THEN WE WERE 3970 02:38:29,955 --> 02:38:33,459 ABLE TO USE THE SAME INNOCULUM 3971 02:38:33,459 --> 02:38:34,760 TO INFECT MULTIPLE ANIMALS. 3972 02:38:34,760 --> 02:38:36,095 FOR THE FIRST ROUND OF STUDIES, 3973 02:38:36,095 --> 02:38:38,263 WE MADE SURE OUR CS AND REA SIP 3974 02:38:38,263 --> 02:38:40,265 YENT MICE WERE ALL JEA KNOW 3975 02:38:40,265 --> 02:38:41,033 TYPE-MATCHED. 3976 02:38:41,033 --> 02:38:42,768 AND I WAS ACTUALLY QUITE 3977 02:38:42,768 --> 02:38:43,969 SURPRISED, I DIDN'T THINK THE 3978 02:38:43,969 --> 02:38:44,737 DIFFERENCES WERE GOING TO BE 3979 02:38:44,737 --> 02:38:45,704 THIS STRIKING. 3980 02:38:45,704 --> 02:38:47,573 WE FOUND THAT OUR WILD TYPE 3981 02:38:47,573 --> 02:38:49,108 ANIMALS GOT MUCH SICKER, SO WHEN 3982 02:38:49,108 --> 02:38:50,743 WE LOOKED AT THEIR MEAN SEPSIS 3983 02:38:50,743 --> 02:38:52,378 SCORE, WHICH IS A MARKER OF 3984 02:38:52,378 --> 02:38:53,912 CLINICAL SEPSIS SEVERITY, THE 3985 02:38:53,912 --> 02:38:55,014 WILD TYPE MICE WERE MUCH MORE 3986 02:38:55,014 --> 02:38:58,050 ILL COMPARED TO THE 3987 02:38:58,050 --> 02:38:58,617 PAD4 DEFICIENT ANIMALS. 3988 02:38:58,617 --> 02:39:01,887 THEY HAD MUCH MORE SEVERE 3989 02:39:01,887 --> 02:39:02,788 THROMBOCYTOPENIA AND THEY HAD 3990 02:39:02,788 --> 02:39:05,290 MUCH MORE SEVERE HYPOTHERMIA, 3991 02:39:05,290 --> 02:39:06,859 WHICH I ACTUALLY REALLY LOVE AS 3992 02:39:06,859 --> 02:39:10,529 A MA MARKER OF SEPSIS SEVERITY. 3993 02:39:10,529 --> 02:39:11,730 THEN WHEN WE LOOKED AT THE 3994 02:39:11,730 --> 02:39:13,065 EXTENT OF BACTERIA 3995 02:39:13,065 --> 02:39:13,932 DISSEMINATION, WE FOUND HIGHER 3996 02:39:13,932 --> 02:39:15,567 LEVELS OF BACTERIA IN THE BLOOD 3997 02:39:15,567 --> 02:39:16,902 OF OUR WILD TYPE ANIMALS 3998 02:39:16,902 --> 02:39:19,505 COMPARED TO OUR PAD4 DEFICIENT 3999 02:39:19,505 --> 02:39:20,806 ANIMALS AND FOUND HIGHER LEVELS 4000 02:39:20,806 --> 02:39:21,707 OF BACTERIA IN THE LIVER. 4001 02:39:21,707 --> 02:39:23,008 SO OF COURSE ALL OF THIS GOES 4002 02:39:23,008 --> 02:39:24,877 CONTRARY TO MY CONFIDENCE THAT 4003 02:39:24,877 --> 02:39:28,347 PAD 4 AND NETS ARE AN IMPORTANT 4004 02:39:28,347 --> 02:39:29,081 EVOLUTIONARY CONSERVED PART OF 4005 02:39:29,081 --> 02:39:34,053 THE INNATE IMMUNE RESPONSE. 4006 02:39:34,053 --> 02:39:35,421 AND I WAS EVEN MORE SURPRISED 4007 02:39:35,421 --> 02:39:38,323 WHEN WE WENT AND DID SURVIVAL 4008 02:39:38,323 --> 02:39:40,192 STUDIES AND FOUND THE KNOCKOUT 4009 02:39:40,192 --> 02:39:42,027 MICE INJECTED WITH KNOCKOUT CS 4010 02:39:42,027 --> 02:39:44,997 HAD 100% SURVIVAL, WHEREAS OUR 4011 02:39:44,997 --> 02:39:47,633 WILD TYPE MICE WITH WILD TYPE CS 4012 02:39:47,633 --> 02:39:48,600 HAD A VERY HIGH RATE OF 4013 02:39:48,600 --> 02:39:48,934 MORTALITY. 4014 02:39:48,934 --> 02:39:51,470 SO WE WERE SCRUNCHING OUR HEADS 4015 02:39:51,470 --> 02:39:52,971 LOOKING AT THIS DATA THINKING IS 4016 02:39:52,971 --> 02:39:54,506 THIS THE PERIPHERAL IMMUNE 4017 02:39:54,506 --> 02:39:56,375 RESPONSE, A PRODUCT OF IMPAIRED 4018 02:39:56,375 --> 02:39:57,676 NET RELEASE THAT'S BEING 4019 02:39:57,676 --> 02:39:59,311 PROTECTIVE OR IS THERE SOMETHING 4020 02:39:59,311 --> 02:40:02,047 GOING ON WITH THE CECAL SLURRY 4021 02:40:02,047 --> 02:40:04,116 BACTERIAL INNOCULUM. 4022 02:40:04,116 --> 02:40:05,984 SO WE LOOKED AT OUR INITIAL 4023 02:40:05,984 --> 02:40:07,519 BASELINE CBC, SO THIS IS LOOKING 4024 02:40:07,519 --> 02:40:08,487 AT THE ANIMALS WHEN THEY WERE 4025 02:40:08,487 --> 02:40:11,890 WELL. 4026 02:40:11,890 --> 02:40:12,891 WE FOUND THERE WAS A LITTLE BIT 4027 02:40:12,891 --> 02:40:15,961 OF A HIGHER WHITE BLOOD CELL 4028 02:40:15,961 --> 02:40:19,798 COUNT IN THE PAD 4 DEFICIENT 4029 02:40:19,798 --> 02:40:20,699 MICE. 4030 02:40:20,699 --> 02:40:23,936 OUR PAD4 DEFICIENT ANIMALS WERE 4031 02:40:23,936 --> 02:40:25,671 NOR NEUTROPHILIC COMPARED TO OUR 4032 02:40:25,671 --> 02:40:26,338 WILD TYPE MICE. 4033 02:40:26,338 --> 02:40:28,240 WE DID SOME PLASMA CYTOKINE 4034 02:40:28,240 --> 02:40:30,809 ANALYSIS AND WE FOUND THAT OUR 4035 02:40:30,809 --> 02:40:31,710 PAD4 DEFICIENT MICE HAD HIGHER 4036 02:40:31,710 --> 02:40:33,679 LEVELS OF INFLAMMATORY 4037 02:40:33,679 --> 02:40:38,050 CYTOKINES, INCLUDING IL-6, IL-1 4038 02:40:38,050 --> 02:40:40,119 BETA, TNF AND IL-17. 4039 02:40:40,119 --> 02:40:42,087 THEY ALSO HAD A REDUCTION IN 4040 02:40:42,087 --> 02:40:44,022 IL23R, THE RECEPTOR FOR IL23, 4041 02:40:44,022 --> 02:40:45,357 WHICH CAN BE DECREASED BY 4042 02:40:45,357 --> 02:40:47,659 INCREASED LEVELS OF IL-17 AND 4043 02:40:47,659 --> 02:40:48,093 IL23. 4044 02:40:48,093 --> 02:40:49,761 AND SINCE THIS PATHWAY IS 4045 02:40:49,761 --> 02:40:50,829 INVOLVED -- WELL-KNOWN TO BE 4046 02:40:50,829 --> 02:40:52,898 INVOLVED IN INFLAMMATORY BOWEL 4047 02:40:52,898 --> 02:40:54,333 DISEASE AND RECRUITMENT OF 4048 02:40:54,333 --> 02:40:55,434 NEUTROPHILS TO THE GUT IN THAT 4049 02:40:55,434 --> 02:40:57,970 CONTEXT, WE DID WANT TO LOOK AT 4050 02:40:57,970 --> 02:40:58,837 THE PATHOLOGY OR SEE IF THERE'S 4051 02:40:58,837 --> 02:41:00,572 ANY PATHOLOGY MOUNTAIN 4052 02:41:00,572 --> 02:41:02,908 INTESTINES OF OUR ANIMALS. 4053 02:41:02,908 --> 02:41:07,546 AND WHILE WE DIDN'T SEE EVIDENCE 4054 02:41:07,546 --> 02:41:09,648 OF EROSIONS OR ABSCESSES OR 4055 02:41:09,648 --> 02:41:10,749 THINGS, WHAT WE DID APPRECIATE 4056 02:41:10,749 --> 02:41:12,918 WHEN WE STAINED THESE SECTIONS 4057 02:41:12,918 --> 02:41:16,221 IS THAT THERE WAS INCREASED 4058 02:41:16,221 --> 02:41:17,089 NEUTROPHIL INFILTRATION AS SHOWN 4059 02:41:17,089 --> 02:41:20,159 IN GREEN HERE, IN THE LAMINA 4060 02:41:20,159 --> 02:41:22,895 PROPRIA OF THE GI TRACT, SO 4061 02:41:22,895 --> 02:41:24,530 INCREASED -- IN OUR PAD 4062 02:41:24,530 --> 02:41:25,497 4 DEFICIENT ANIMALS. 4063 02:41:25,497 --> 02:41:28,233 THEN WE DID SOME MICROBIAL 4064 02:41:28,233 --> 02:41:29,568 SEQUENCING OF THE CECAL CONTENT 4065 02:41:29,568 --> 02:41:33,839 OF OUR WILD TYPE VERSUS OUR PAD. 4066 02:41:33,839 --> 02:41:35,140 IN LOOKING AT THE RELATIVE 4067 02:41:35,140 --> 02:41:36,675 ABUNDANCE OF DIFFERENT BACTERIA, 4068 02:41:36,675 --> 02:41:37,876 WE FOUND THAT THERE WERE 4069 02:41:37,876 --> 02:41:38,877 STRIKING DIFFERENCES BETWEEN 4070 02:41:38,877 --> 02:41:41,914 THESE ANIMALS AND WHEN WE DID A 4071 02:41:41,914 --> 02:41:43,782 PCA ANALYSIS, YOU CAN SEE THEY 4072 02:41:43,782 --> 02:41:45,117 CLUSTER INDEPENDENTLY WITH THE 4073 02:41:45,117 --> 02:41:48,687 PAD 4 ANIMALS IN RED, NOOKOUT 4074 02:41:48,687 --> 02:41:52,658 WILD TYPEANIMALS IN BLUE. 4075 02:41:52,658 --> 02:41:53,592 SO DETERMINE IF THESE 4076 02:41:53,592 --> 02:41:54,693 DIFFERENCES THAT WE WERE SEEING 4077 02:41:54,693 --> 02:41:56,028 WERE PHYSIOLOGICALLY RELEVANT OR 4078 02:41:56,028 --> 02:41:58,096 RELEVANT TO THE OBSERVED 4079 02:41:58,096 --> 02:41:59,865 DIFFERENCES IN OUTCOME, WE ENDED 4080 02:41:59,865 --> 02:42:01,300 UP TREATING OUR WILD TYPE 4081 02:42:01,300 --> 02:42:06,305 ANIMALS WITH CS FROM BAD PAD 4082 02:42:06,305 --> 02:42:09,708 4 DEFICIENT MICE. 4083 02:42:09,708 --> 02:42:11,543 AND WHAT WE DID FIND IS THAT, 4084 02:42:11,543 --> 02:42:13,645 AGAIN, WHEN ANIMALS RECEIVED 4085 02:42:13,645 --> 02:42:16,048 GENOTYPE MATCH CS WILD TYPE 4086 02:42:16,048 --> 02:42:17,683 ANIMALS THAT GOT WILD TYPE CS 4087 02:42:17,683 --> 02:42:19,318 WERE SICKER THAN PAD 4 KNOCKOUT 4088 02:42:19,318 --> 02:42:20,419 ANIMALS THAT GOT. 4089 02:42:20,419 --> 02:42:22,154 CS FROM PAD 4 KNOCKOUT MICE. 4090 02:42:22,154 --> 02:42:23,589 WHEN EVERYBODY RECEIVED WILD 4091 02:42:23,589 --> 02:42:25,457 TYPE CECAL SLURRY THEY BECAME 4092 02:42:25,457 --> 02:42:27,092 EQUALLY ILL AND WHEN EVERY MOUSE 4093 02:42:27,092 --> 02:42:30,062 RECEIVED PAD 4 KNOCKOUT CECAL 4094 02:42:30,062 --> 02:42:32,197 SLURRY, THEY HAD AN EQUAL SORT 4095 02:42:32,197 --> 02:42:33,332 OF DECREASE IN THE SEVERITY OF 4096 02:42:33,332 --> 02:42:34,766 SEPSIS. 4097 02:42:34,766 --> 02:42:36,702 AND THIS ALSO HELD TRUE WITH 4098 02:42:36,702 --> 02:42:38,670 EVIDENCE OF BACTEREMIA WITH, 4099 02:42:38,670 --> 02:42:40,639 AGAIN, EQUAL LEVELS OF 4100 02:42:40,639 --> 02:42:41,974 BACTEREMIA OF ANIMALS THAT 4101 02:42:41,974 --> 02:42:43,609 RECEIVED WILD TYPE CS AND 4102 02:42:43,609 --> 02:42:46,445 REDUCTION OF BA BACTEREMIA IN BH 4103 02:42:46,445 --> 02:42:47,980 WILD TYPES THAT RECEIVED 4104 02:42:47,980 --> 02:42:48,413 KNOCKOUT CS. 4105 02:42:48,413 --> 02:42:49,715 THEN WHEN WE WENT BACK TO LOOK 4106 02:42:49,715 --> 02:42:51,383 AT SURVIVAL, THIS IS JUST A 4107 02:42:51,383 --> 02:42:53,018 LITTLE REMINDER OF THE BASELINE 4108 02:42:53,018 --> 02:42:54,453 SURVIVAL WITH THAT REAL 4109 02:42:54,453 --> 02:42:55,854 PROTECTION IN THE KNOCKOUT MICE 4110 02:42:55,854 --> 02:42:58,690 THAT GOT KNOCKOUT CS. 4111 02:42:58,690 --> 02:43:01,560 BUT WHEN WE SWITCHED THE -- WHEN 4112 02:43:01,560 --> 02:43:03,729 WE DO THESE GENOTYPE SWAPS, WHAT 4113 02:43:03,729 --> 02:43:04,830 WE FOUND IS THAT OUR KNOCKOUT 4114 02:43:04,830 --> 02:43:06,898 MICE HAD EQUAL TO MORE SEVERE 4115 02:43:06,898 --> 02:43:08,200 MORTALITY TO OUR WILD TYPE MICE 4116 02:43:08,200 --> 02:43:10,168 WHEN THEY BOTH RECEIVED WILD 4117 02:43:10,168 --> 02:43:12,704 TYPE CS, AND THE WILD TYPE MICE 4118 02:43:12,704 --> 02:43:14,873 THAT RECEIVED KNOCKOUT CS HAD 4119 02:43:14,873 --> 02:43:16,508 PROTECTION FROM MORTALITY. 4120 02:43:16,508 --> 02:43:17,843 SO NOT COMPLETELY RESTORED TO 4121 02:43:17,843 --> 02:43:19,711 THE LEVELS OF THE PAD 4122 02:43:19,711 --> 02:43:21,680 4 DEFICIENT MICE, BUT MUCH 4123 02:43:21,680 --> 02:43:23,415 BETTER THAN THEIR COHORT THAT 4124 02:43:23,415 --> 02:43:26,918 RECEIVED WILD TYPE CS. 4125 02:43:26,918 --> 02:43:29,321 SO JUST TO SUMMARIZE, THERE'S 4126 02:43:29,321 --> 02:43:31,089 ACTIVE RESEARCH INTO MULTIPLE 4127 02:43:31,089 --> 02:43:32,391 DIRECTED THERAPEUTIC STRATEGIES. 4128 02:43:32,391 --> 02:43:34,459 ALL OF WHICH HAVE SOME UNIQUE 4129 02:43:34,459 --> 02:43:35,661 ADVANTAGES AND DISADVANTAGES, 4130 02:43:35,661 --> 02:43:39,398 AND I SUSPECT THAT WE'LL GET 4131 02:43:39,398 --> 02:43:41,900 INTO THIS IN THE NEXT TALK. 4132 02:43:41,900 --> 02:43:43,769 NET MODIFICATION WITH PLATELET 4133 02:43:43,769 --> 02:43:45,404 FACTOR 4 CAUSES NETS TO BECOME 4134 02:43:45,404 --> 02:43:46,705 COMPACT AND RESISTANT TO 4135 02:43:46,705 --> 02:43:50,342 NUCLEASE DIGESTION WHICH IN TURN 4136 02:43:50,342 --> 02:43:53,278 LIMITS THEIR THROMBOTIC 4137 02:43:53,278 --> 02:43:57,316 POTENTIAL, AND PAD 4 DEFICIENT 4138 02:43:57,316 --> 02:43:58,517 MICE HAVE INTERESTING CHANGES IN 4139 02:43:58,517 --> 02:44:00,719 THEIR BASELINE INFLAMMATION, 4140 02:44:00,719 --> 02:44:02,254 CHANGES IN TISSUE INFILTRATION 4141 02:44:02,254 --> 02:44:03,889 AND ALSO INTERESTING CHANGES IN 4142 02:44:03,889 --> 02:44:05,557 THE COMPOSITION OF THEIR GI 4143 02:44:05,557 --> 02:44:07,626 MICRO BUY YOAM THAT IN TURN 4144 02:44:07,626 --> 02:44:08,794 INFLUENCE -- I THINK THESE 4145 02:44:08,794 --> 02:44:09,795 CHANGES INFLUENCE SURVIVAL TO 4146 02:44:09,795 --> 02:44:12,097 SOME EXTENT IN THE CECAL 4147 02:44:12,097 --> 02:44:13,832 LIGATION PUNCTURE MODEL OF 4148 02:44:13,832 --> 02:44:14,933 SEPSIS, AND ALTHOUGH THESE 4149 02:44:14,933 --> 02:44:16,568 FINDINGS WERE PREVIOUSLY 4150 02:44:16,568 --> 02:44:18,970 ATTRIBUTED EXCLUSIVELY TO 4151 02:44:18,970 --> 02:44:21,039 PROTECTION FROM SOME OF THE 4152 02:44:21,039 --> 02:44:22,474 IMMUNOTHROMBOTIC EFFECTS OF NET 4153 02:44:22,474 --> 02:44:23,275 RELEASE, I'D SUSPECT THAT SOME 4154 02:44:23,275 --> 02:44:26,311 OF THIS WAS RELATED TO CHANGES 4155 02:44:26,311 --> 02:44:28,080 IN THE COMPOSITION OF THE 4156 02:44:28,080 --> 02:44:30,349 INFECTIOUS INNOCULUM IN THAT 4157 02:44:30,349 --> 02:44:30,916 MODEL. 4158 02:44:30,916 --> 02:44:32,984 IN OUR HANDS WE OBSERVED 4159 02:44:32,984 --> 02:44:34,953 OUTCOMES IN THE CECAL SLURRY 4160 02:44:34,953 --> 02:44:37,055 MODEL ARE INFLUENCED BY BOTH PAD 4161 02:44:37,055 --> 02:44:38,123 4 EXPRESSION IN THE C SDOH NOR 4162 02:44:38,123 --> 02:44:40,525 AS WELL AS TO SOME EXTENT PAD 4163 02:44:40,525 --> 02:44:41,827 4 EXPRESSION IN THE RECIPIENT 4164 02:44:41,827 --> 02:44:42,060 ANIMALS. 4165 02:44:42,060 --> 02:44:45,430 SO I THINK THAT THIS DATA WILL 4166 02:44:45,430 --> 02:44:46,965 SORT OF MAYBE HELP US UNDERSTAND 4167 02:44:46,965 --> 02:44:48,734 WHAT SOME OF THE EFFECTS OF 4168 02:44:48,734 --> 02:44:50,502 PROLONGED NET INHIBITION MIGHT 4169 02:44:50,502 --> 02:44:52,771 BE, BUT ALSO WILL INFORM OUR 4170 02:44:52,771 --> 02:44:53,338 UNDERSTANDING OF THE RESULTS 4171 02:44:53,338 --> 02:44:55,540 THAT WE SEE IN DIFFERENT MODELS 4172 02:44:55,540 --> 02:44:58,477 OF POLYMICROBIAL SEPSIS. 4173 02:44:58,477 --> 02:45:00,345 I JUST WANT TO THANK THE LARGER 4174 02:45:00,345 --> 02:45:01,747 GROUP AND FUNDING SOURCES THAT 4175 02:45:01,747 --> 02:45:03,181 HAVE CONTRIBUTED TO THIS WORK 4176 02:45:03,181 --> 02:45:04,483 AND LOOKING FORWARD TO THE 4177 02:45:04,483 --> 02:45:05,350 CONTRIBUTION AT THE END OF THE 4178 02:45:05,350 --> 02:45:09,221 SESSION. 4179 02:45:09,221 --> 02:45:12,791 >> THANK YOU VERY MUCH, THIS IS 4180 02:45:12,791 --> 02:45:14,192 A FANTASTIC AND WONDERFUL 4181 02:45:14,192 --> 02:45:16,061 PRESENTATION. 4182 02:45:16,061 --> 02:45:16,628 I THINK -- 4183 02:45:16,628 --> 02:45:18,730 >> I THINK I CAN -- 4184 02:45:18,730 --> 02:45:20,065 >> INTRODUCE OUR LAST SPEAKER. 4185 02:45:20,065 --> 02:45:21,733 THANK YOU. 4186 02:45:21,733 --> 02:45:24,836 >> SO OUR LAST SPEAKER OF THIS 4187 02:45:24,836 --> 02:45:30,175 SESSION IS DR. PATRICIA LIAW, 4188 02:45:30,175 --> 02:45:31,276 PROFESSOR OF DEPARTMENT OF 4189 02:45:31,276 --> 02:45:32,711 MEDICINE AT MCMASTER UNIVERSITY. 4190 02:45:32,711 --> 02:45:33,912 SHE'LL BE TALKING ABOUT 4191 02:45:33,912 --> 02:45:36,415 THERAPEUTIC STRATEGIES TO TARGET 4192 02:45:36,415 --> 02:45:37,616 IMMUNOTHROMBOSIS IN SEPSIS. 4193 02:45:37,616 --> 02:45:38,383 EVERYONE PLEASE POST YOUR 4194 02:45:38,383 --> 02:45:40,652 QUESTIONS IN THE CHAT BOX AND WE 4195 02:45:40,652 --> 02:45:44,189 WILL HAVE THEM ADDRESSED DURING 4196 02:45:44,189 --> 02:45:45,290 THE DISCUSSION SECTION. 4197 02:45:45,290 --> 02:45:48,894 THANK YOU VERY MUCH, PLEASE. 4198 02:45:48,894 --> 02:45:51,296 >> GOOD AFTERNOON. 4199 02:45:51,296 --> 02:45:51,963 HI, EVERYONE. 4200 02:45:51,963 --> 02:45:53,398 VERY PLEASED TO BE INVITED TO 4201 02:45:53,398 --> 02:45:58,103 GIVE A TALK IN THIS FASCINATED, 4202 02:45:58,103 --> 02:45:59,504 VERY INFORMATIVE AND UP TO DATE 4203 02:45:59,504 --> 02:46:01,139 SESSION ON IMMUNOTHROMBOSIS. 4204 02:46:01,139 --> 02:46:05,644 SO MY PRESENTATION FOCUSES ON 4205 02:46:05,644 --> 02:46:09,481 THERAPEUTIC -- TO TARGET -- 4206 02:46:09,481 --> 02:46:10,348 IMMUNOTHROMBOSIS AND SEPSIS. 4207 02:46:10,348 --> 02:46:18,023 IS MY AUDIO OKAY? 4208 02:46:18,023 --> 02:46:19,658 >> I THINK WE CAN HEAR YOU. 4209 02:46:19,658 --> 02:46:24,596 I THINK SOMEONE'S SPEAKER IS ON. 4210 02:46:24,596 --> 02:46:26,064 >> WONDERFUL. 4211 02:46:26,064 --> 02:46:31,036 NEXT SLIDE, PLEASE? 4212 02:46:31,036 --> 02:46:32,437 SO THE PRESENTATION LEARNING 4213 02:46:32,437 --> 02:46:33,972 OBJECTIVES ARE TO UNDERSTAND 4214 02:46:33,972 --> 02:46:37,142 SOME OF THE BARRIERS TO SUCCESS 4215 02:46:37,142 --> 02:46:39,010 OF CLINICAL TRIALS IN SEPSIS, TO 4216 02:46:39,010 --> 02:46:43,181 IDENTIFY THERAPEUTIC STRATEGIES 4217 02:46:43,181 --> 02:46:45,650 THAT TARGET MULTIPLE PATHWAYS 4218 02:46:45,650 --> 02:46:46,651 AND TO UNDERSTAND THE BENEFITS 4219 02:46:46,651 --> 02:46:49,221 OF ENRICHMENT STRATEGIES IN 4220 02:46:49,221 --> 02:46:59,664 CLINICAL TRIALS IN SEPSIS. 4221 02:47:00,499 --> 02:47:02,100 SO AS WE HEARD IN THE FIRST 4222 02:47:02,100 --> 02:47:04,402 SESSION, SEPSIS IS DEFINED AS A 4223 02:47:04,402 --> 02:47:05,604 LIFE-THREATENING ORGAN 4224 02:47:05,604 --> 02:47:06,805 DYSFUNCTION DUE TO A 4225 02:47:06,805 --> 02:47:08,206 DYSREGULATED HOST RESPONSE TO 4226 02:47:08,206 --> 02:47:09,741 INFECTION. 4227 02:47:09,741 --> 02:47:10,976 THERE ARE MANY DIFFERENT SITES 4228 02:47:10,976 --> 02:47:12,811 OF INFECTION AS WELL AS TYPES OF 4229 02:47:12,811 --> 02:47:13,445 MICROORGANISMS. 4230 02:47:13,445 --> 02:47:14,846 IT'S A LEADING CAUSE OF DEATH IN 4231 02:47:14,846 --> 02:47:16,748 THE ICU WITH MORTALITY RATES OF 4232 02:47:16,748 --> 02:47:21,486 UP TO 50% FOR PATIENTS WITH 4233 02:47:21,486 --> 02:47:24,756 SEPTIC SHOCK, OVER 11 MILLION 4234 02:47:24,756 --> 02:47:30,028 DEATHS WORLDWIDE. 4235 02:47:30,028 --> 02:47:31,196 IMMUNOTHROMBOSIS IS CONSIDERED A 4236 02:47:31,196 --> 02:47:32,631 BIN FICIAL MECHANISM OF INNATE 4237 02:47:32,631 --> 02:47:33,064 IMMUNITY. 4238 02:47:33,064 --> 02:47:35,133 IT INVOLVES THE ACTIVE 4239 02:47:35,133 --> 02:47:37,669 PARTICIPATION OF IMMUNE CELLS 4240 02:47:37,669 --> 02:47:38,837 WHICH FACILITATES THE 4241 02:47:38,837 --> 02:47:39,938 RECOGNITION, CONTAINMENT AND 4242 02:47:39,938 --> 02:47:42,908 DESTRUCTION OF PATHOGENS BUT 4243 02:47:42,908 --> 02:47:44,776 HAVE LEFT DYSREGULATED, IT CAN 4244 02:47:44,776 --> 02:47:47,145 ALSO BE A DRIVER OF 4245 02:47:47,145 --> 02:47:52,317 INTRAVASCULAR THROMBOSIS. 4246 02:47:52,317 --> 02:47:54,452 THIS DIAGRAM DESCRIBES SOME OF 4247 02:47:54,452 --> 02:47:56,054 THE COMMON MECHANISMS BY WHICH 4248 02:47:56,054 --> 02:47:57,889 MICROBES COULD INDUCE 4249 02:47:57,889 --> 02:47:58,423 IMMUNOTHROMBOSIS. 4250 02:47:58,423 --> 02:48:01,393 SO REGARDLESS OF THE SOURCE OF 4251 02:48:01,393 --> 02:48:02,694 INFECTION, WHETHER IT'S 4252 02:48:02,694 --> 02:48:05,330 BACTERIAL OR VIRAL, THE 4253 02:48:05,330 --> 02:48:09,267 PATHOGENS WILL UPREGULATE TISSUE 4254 02:48:09,267 --> 02:48:11,836 FACTOR EXPRESSION ON MONOCYTES 4255 02:48:11,836 --> 02:48:16,274 IN THE CASE OF BACTERIA, OR 4256 02:48:16,274 --> 02:48:17,342 THEY -- THAT LEADS TO THE 4257 02:48:17,342 --> 02:48:18,777 ACTIVATION OF COAGULATION AND 4258 02:48:18,777 --> 02:48:21,179 ALSO THE PRODUCTION OF 4259 02:48:21,179 --> 02:48:23,815 CYTOKINES, WHICH WILL CAUSE 4260 02:48:23,815 --> 02:48:25,016 SYSTEMIC ENDOTHELIAL INJURY. 4261 02:48:25,016 --> 02:48:27,519 THE ACTIVATED ENDOTHELIAL 4262 02:48:27,519 --> 02:48:33,558 SURFACE WILL RELEASE ULTRA -- 4263 02:48:33,558 --> 02:48:34,526 VON WILLEBRAND FACTOR, LEADING 4264 02:48:34,526 --> 02:48:36,161 TO PLATELET ACTIVATION AND ALSO 4265 02:48:36,161 --> 02:48:38,997 THE RELEASE OF NEUTROPHIL 4266 02:48:38,997 --> 02:48:41,633 EXTRACELLULAR TRAPS, WHICH WAS 4267 02:48:41,633 --> 02:48:43,068 NICELY SUMMARIZED IN THE 4268 02:48:43,068 --> 02:48:43,735 PREVIOUS PRESENTATION. 4269 02:48:43,735 --> 02:48:45,570 THE NET RESULT IS 4270 02:48:45,570 --> 02:48:47,439 IMMUNOTHROMBOSIS IN WHICH THE 4271 02:48:47,439 --> 02:48:49,874 CLOT CONSISTS NOT ONLY OF 4272 02:48:49,874 --> 02:48:51,710 PLATELETS AND FIBRIN, BUT ALSO 4273 02:48:51,710 --> 02:48:54,145 IMMUNE CELLS, NOTE PLI 4274 02:48:54,145 --> 02:48:56,948 > NOTABLY 4275 02:48:56,948 --> 02:49:01,119 NEUTROPHILS MONOCYTES AND THEIR 4276 02:49:01,119 --> 02:49:11,396 COMPONENTS, AND HISTONES. 4277 02:49:11,396 --> 02:49:13,531 SO THERE HAD BEEN OVER 60 4278 02:49:13,531 --> 02:49:14,199 RANDOMIZED CONTROL CLINICAL 4279 02:49:14,199 --> 02:49:15,533 TRIALS IN SEPSIS OVER THE PAST 4280 02:49:15,533 --> 02:49:18,336 THREE DECADES INVOLVING OVER 4281 02:49:18,336 --> 02:49:21,773 22,000 PATIENTS. 4282 02:49:21,773 --> 02:49:23,308 HOWEVER, NONE HAVE RESULTED IN 4283 02:49:23,308 --> 02:49:25,276 NEW TREATMENT STRATEGIES. 4284 02:49:25,276 --> 02:49:26,277 THE INTERVENTIONS INCLUDE 4285 02:49:26,277 --> 02:49:27,579 STRATEGIES TO REDUCE 4286 02:49:27,579 --> 02:49:30,448 INFLAMMATION OR TO NEUTRALIZE 4287 02:49:30,448 --> 02:49:34,486 BACTERIAL EN ENDO TOXINS, AS WEL 4288 02:49:34,486 --> 02:49:35,920 AS ANTICOAGULANTS, WHICH I'LL 4289 02:49:35,920 --> 02:49:38,023 DESCRIBE A LITTLE MORE LATER ON 4290 02:49:38,023 --> 02:49:40,792 IN THE PRESENTATION. 4291 02:49:40,792 --> 02:49:42,661 SO WHY HAVE CLINICAL TRIALS 4292 02:49:42,661 --> 02:49:43,928 FAILED IN SEPSIS? 4293 02:49:43,928 --> 02:49:46,498 THERE ARE POTENTIAL REASONS 4294 02:49:46,498 --> 02:49:49,768 INCLUDING THE CHOICE OF TIMING 4295 02:49:49,768 --> 02:49:50,669 AND THE DOSE. 4296 02:49:50,669 --> 02:49:52,604 SO THE ONSET OF SEPSIS AND DIC 4297 02:49:52,604 --> 02:49:54,172 ARE ILL DEFINED AND THE TARGET 4298 02:49:54,172 --> 02:49:55,473 OF THERAPY MAY CHANGE OVER TIME 4299 02:49:55,473 --> 02:49:57,642 DUE TO DISEASE EVOLUTION. 4300 02:49:57,642 --> 02:49:58,743 THE SECOND REASON IS THE CHOICE 4301 02:49:58,743 --> 02:50:00,045 OF INTERVENTION. 4302 02:50:00,045 --> 02:50:01,913 WHAT IS THE BEST ANIMAL MODEL TO 4303 02:50:01,913 --> 02:50:04,349 USE, WHAT IS THE CORRECT TARGET, 4304 02:50:04,349 --> 02:50:07,085 AND WILL SINGLE THERAPIES BE 4305 02:50:07,085 --> 02:50:07,952 EFFECTIVE GIVEN THE COMPLEX 4306 02:50:07,952 --> 02:50:09,921 NATURE OF THE IMMUNE RESPONSE IN 4307 02:50:09,921 --> 02:50:10,321 SEPSIS? 4308 02:50:10,321 --> 02:50:12,857 AND THEN FINALLY, THE CHOICE OF 4309 02:50:12,857 --> 02:50:13,425 POPULATION. 4310 02:50:13,425 --> 02:50:15,927 SO THERE'S HETEROGENEITY IN 4311 02:50:15,927 --> 02:50:18,229 PATIENTS AS WELL AS PROCESS OF 4312 02:50:18,229 --> 02:50:19,564 CARE AND STRATIFICATION SYSTEMS 4313 02:50:19,564 --> 02:50:21,433 MAY BE NEEDED TO GUIDE TREATMENT 4314 02:50:21,433 --> 02:50:26,604 DECISIONS. 4315 02:50:26,604 --> 02:50:33,144 IN TERMS OF THE TIMING, BECAUSE 4316 02:50:33,144 --> 02:50:34,646 SEPSIS IS A CONTINUUM, THE 4317 02:50:34,646 --> 02:50:36,081 TIMING OF THEIR PEES MAY AFFECT 4318 02:50:36,081 --> 02:50:36,614 THEIR EFFICACY. 4319 02:50:36,614 --> 02:50:40,585 SO THE INITIAL INFECTION MAY BE 4320 02:50:40,585 --> 02:50:41,453 LOCALIZED, BUT WHEN THE 4321 02:50:41,453 --> 02:50:43,188 INFECTION IS DYSREGULATED AND 4322 02:50:43,188 --> 02:50:44,723 SYSTEMIC, THAT COULD LEAD TO 4323 02:50:44,723 --> 02:50:46,825 SEPSIS, SEPTIC SHOCK, MULTIPLE 4324 02:50:46,825 --> 02:50:48,026 ORGAN FAILURE, AND FINALLY, 4325 02:50:48,026 --> 02:50:50,095 DEATH. 4326 02:50:50,095 --> 02:50:52,363 IN RECENT YEARS, THERE HAVE BEEN 4327 02:50:52,363 --> 02:50:54,466 RENEWED INTEREST IN REVISITING 4328 02:50:54,466 --> 02:50:55,333 HEPARIN AS A POTENTIAL THERAPY 4329 02:50:55,333 --> 02:50:56,101 FOR SEPSIS. 4330 02:50:56,101 --> 02:51:06,644 HEPARIN IS A NEGATIVELY CHARGED 4331 02:51:07,078 --> 02:51:08,146 GLYCOSAMINOGLYCAN. 4332 02:51:08,146 --> 02:51:10,982 IT ALSO HAS ANTI-INFLAMMATORY, 4333 02:51:10,982 --> 02:51:11,850 ANTIMICROBIAL PROPERTIES. 4334 02:51:11,850 --> 02:51:14,052 IF WE LOOK AT THIS DIAGRAM, YOU 4335 02:51:14,052 --> 02:51:16,488 CAN SEE THAT HEPARIN CAN TARGET 4336 02:51:16,488 --> 02:51:17,956 MULTIPLE PATHWAYS, SO IN 4337 02:51:17,956 --> 02:51:19,524 ADDITION TO INHIBITING CLOTTING, 4338 02:51:19,524 --> 02:51:23,027 IT HAS THE ABILITY TO NEUTRALIZE 4339 02:51:23,027 --> 02:51:24,796 THE TOXIC EFFECTS OF 4340 02:51:24,796 --> 02:51:25,864 EXTRACELLULAR HISTONES, AND 4341 02:51:25,864 --> 02:51:29,467 THROUGH THIS, IT CAN REDUCE 4342 02:51:29,467 --> 02:51:31,336 TISSUE FACTOR EXPRESSION ON 4343 02:51:31,336 --> 02:51:33,872 MONOCYTES, PREVENT ENDOTHELIAL 4344 02:51:33,872 --> 02:51:35,707 CELL DEATH AND ALSO PREVENT 4345 02:51:35,707 --> 02:51:36,941 PLATELET ACTIVATION. 4346 02:51:36,941 --> 02:51:39,677 THERE HAVE BEEN MAJOR RANDOMIZED 4347 02:51:39,677 --> 02:51:42,847 CONTROL TRIALS EXAMINING THE 4348 02:51:42,847 --> 02:51:44,149 PROTECTIVE EFFECTS OF 4349 02:51:44,149 --> 02:51:45,784 THERAPEUTIC DOSE 4350 02:51:45,784 --> 02:51:47,318 ANTI-COAGULATION IN PATIENTS 4351 02:51:47,318 --> 02:51:56,027 WITH COVID-19-RELATED SEPSIS. 4352 02:51:56,027 --> 02:51:57,562 WHAT HAS EMERGED FROM THESE 4353 02:51:57,562 --> 02:51:58,863 TRIALS IS THAT THERAPEUTIC DOSE 4354 02:51:58,863 --> 02:52:00,532 HEPARIN APPEARS TO BE BENEFICIAL 4355 02:52:00,532 --> 02:52:03,034 IN MODERATELY ILL BUT NOT IN 4356 02:52:03,034 --> 02:52:04,569 CRITICALLY ILL PATIENTS WITH 4357 02:52:04,569 --> 02:52:09,073 COVID-19-RELATED SEPSIS. 4358 02:52:09,073 --> 02:52:10,441 THERE'VE ALSO BEEN CLINICAL 4359 02:52:10,441 --> 02:52:13,611 TRIALS LOOKING AT IL-6 RECEPTOR 4360 02:52:13,611 --> 02:52:14,212 ANTAGONISTS. 4361 02:52:14,212 --> 02:52:16,414 IL-6 IS AN INFLAMMATORY CYTOKINE 4362 02:52:16,414 --> 02:52:17,549 RELEASED IN RESPONSE TO 4363 02:52:17,549 --> 02:52:17,949 INFECTION. 4364 02:52:17,949 --> 02:52:20,051 IT'S PART OF THE ACUTE PHASE 4365 02:52:20,051 --> 02:52:20,885 RESPONSE. 4366 02:52:20,885 --> 02:52:22,387 THERE ARE MONOCLONAL ANTIBODIES 4367 02:52:22,387 --> 02:52:25,156 THAT CAN INHIBIT BOTH THE 4368 02:52:25,156 --> 02:52:26,257 MEMBRANE BOUND AS WELL AS THE 4369 02:52:26,257 --> 02:52:30,628 SOLUBLE FORM OF INTERLEUKIN 6. 4370 02:52:30,628 --> 02:52:32,630 THE RESULTS OF CLINICAL TRIALS 4371 02:52:32,630 --> 02:52:35,433 RESULTS THAT IL-6 RECEPTOR 4372 02:52:35,433 --> 02:52:36,634 ANTAGONIST IS BENEFICIAL IN 4373 02:52:36,634 --> 02:52:38,069 CRITICALLY ILL PATIENTS WITH 4374 02:52:38,069 --> 02:52:41,673 COVID-19-RELATED SEPSIS. 4375 02:52:41,673 --> 02:52:44,509 SO WE GO BACK TO THIS CONTINUUM. 4376 02:52:44,509 --> 02:52:46,477 IT SUGGESTS THAT THERE ARE 4377 02:52:46,477 --> 02:52:47,812 THERAPIES SUCH AS HEPARIN THAT 4378 02:52:47,812 --> 02:52:50,548 MAY BE BENEFICIAL IN THE EARLY 4379 02:52:50,548 --> 02:52:52,750 PHASE OF SEPSIS, AS THERAPIES 4380 02:52:52,750 --> 02:52:54,586 SUCH AS ALL SIX RECEPTOR 4381 02:52:54,586 --> 02:52:55,854 ANTAGONISTS MAY BE BENEFICIAL IN 4382 02:52:55,854 --> 02:53:00,625 THE LATER STAGES. 4383 02:53:00,625 --> 02:53:02,594 SO WHAT ABOUT THE CHOICE OF 4384 02:53:02,594 --> 02:53:03,027 INTERVENTION? 4385 02:53:03,027 --> 02:53:05,096 WHAT IS THE BEST ANIMAL MODEL TO 4386 02:53:05,096 --> 02:53:06,764 USE? 4387 02:53:06,764 --> 02:53:09,500 ARE THERE DIFFERENT TARGETS THAT 4388 02:53:09,500 --> 02:53:11,236 MAY BE CONSIDERED NOVEL 4389 02:53:11,236 --> 02:53:14,739 THERAPIES? 4390 02:53:14,739 --> 02:53:16,574 THERE ARE METHODOLOGICAL 4391 02:53:16,574 --> 02:53:18,910 CHALLENGES OF PRE-CLINICAL 4392 02:53:18,910 --> 02:53:21,212 ANIMAL RESEARCH. 4393 02:53:21,212 --> 02:53:22,614 IN PRE-CLINICAL RESEARCH, THE 4394 02:53:22,614 --> 02:53:24,716 STUDIES ARE USUALLY SINGLE 4395 02:53:24,716 --> 02:53:26,784 CENTER, THEY'RE NOT RANDOMIZED 4396 02:53:26,784 --> 02:53:27,652 OR BLINDED. 4397 02:53:27,652 --> 02:53:29,087 SOMETIMES SAMPLE SIZE 4398 02:53:29,087 --> 02:53:31,589 CALCULATIONS ARE NOT PROVIDED. 4399 02:53:31,589 --> 02:53:34,325 THERE'S VARIATIONS IN PROTOCOL, 4400 02:53:34,325 --> 02:53:35,460 AND INCOMPLETE REPORTING, WHICH 4401 02:53:35,460 --> 02:53:37,395 MAKES THE STUDIES DIFFICULT TO 4402 02:53:37,395 --> 02:53:38,796 REPRODUCE BETWEEN CENTERS. 4403 02:53:38,796 --> 02:53:40,798 IN CONTRAST, CLINICAL RESEARCH 4404 02:53:40,798 --> 02:53:43,768 IS OFTEN MULTICENTER RANDOMIZED 4405 02:53:43,768 --> 02:53:45,970 ADEQUATELY POWERED WITH SHARED 4406 02:53:45,970 --> 02:53:47,005 PROTOCOLS AND STANDARDIZED 4407 02:53:47,005 --> 02:53:51,409 REPORTING. 4408 02:53:51,409 --> 02:53:54,712 SO TO ADDRESS SOME OF THE 4409 02:53:54,712 --> 02:53:55,914 LIMITATIONS IN PRE-CLINICAL 4410 02:53:55,914 --> 02:53:59,284 ANIMAL STUDIES OF SEPSIS, IN 4411 02:53:59,284 --> 02:54:00,985 2019, WE ESTABLISHED THE 4412 02:54:00,985 --> 02:54:03,588 NATIONAL PRE-CLINICAL SEPSIS 4413 02:54:03,588 --> 02:54:06,424 PLATFORM, WHICH IS A 4414 02:54:06,424 --> 02:54:08,393 COLLABORATIVE NETWORK OF 4415 02:54:08,393 --> 02:54:10,495 CANADIAN SEPSIS RESEARCHERS AND 4416 02:54:10,495 --> 02:54:12,563 VETERINARIANS TO CREATE A 4417 02:54:12,563 --> 02:54:13,665 MULTICENTER INFRASTRUCTURE TO 4418 02:54:13,665 --> 02:54:15,300 RIGOROUSLY STUDY THE 4419 02:54:15,300 --> 02:54:17,735 PATHOPHYSIOLOGY OF SEPSIS AND TO 4420 02:54:17,735 --> 02:54:19,470 ACCELERATE THE MOVEMENT OF 4421 02:54:19,470 --> 02:54:20,471 PROMISING THERAPIES INTO EARLY 4422 02:54:20,471 --> 02:54:24,175 PHASE CLINICAL TRIALS. 4423 02:54:24,175 --> 02:54:27,378 SO THE SCIENTIFIC GOALS OF THE 4424 02:54:27,378 --> 02:54:29,113 NATIONAL PLATFORM ARE TO CREATE 4425 02:54:29,113 --> 02:54:29,981 A MULTI-LABORATORY 4426 02:54:29,981 --> 02:54:32,183 INFRASTRUCTURE TO EVALUATE THE 4427 02:54:32,183 --> 02:54:33,384 PATHOPHYSIOLOGY OF THEIR HOST 4428 02:54:33,384 --> 02:54:34,919 RESPONSE AS WELL AS THE 4429 02:54:34,919 --> 02:54:36,220 BIOLOGICAL HETEROGENEITY OF 4430 02:54:36,220 --> 02:54:37,755 SEPSIS IN A CONTROLLED 4431 02:54:37,755 --> 02:54:40,758 PRE-CLINICAL ENVIRONMENT. 4432 02:54:40,758 --> 02:54:41,926 ALSO TO IDENTIFY RESEARCH GOALS 4433 02:54:41,926 --> 02:54:45,229 THAT ARE CLINICALLY RELEVANT AND 4434 02:54:45,229 --> 02:54:46,331 PATIENT-CENTERED, ULTIMATELY TO 4435 02:54:46,331 --> 02:54:48,399 ACCELERATE THE MOVEMENT OF NOVEL 4436 02:54:48,399 --> 02:54:49,400 THERAPEUTICS INTO EARLY CLINICAL 4437 02:54:49,400 --> 02:54:54,739 TESTING. 4438 02:54:54,739 --> 02:54:55,873 THIS JUST SHOWS SOME OF THE 4439 02:54:55,873 --> 02:54:57,408 CENTERS THAT ARE PARTICIPATING 4440 02:54:57,408 --> 02:55:03,314 IN THE NATIONAL PRE-CLINICAL 4441 02:55:03,314 --> 02:55:04,282 SEPSIS PLATFORM. 4442 02:55:04,282 --> 02:55:05,283 SO ONE OF THE MODELS THAT WE'VE 4443 02:55:05,283 --> 02:55:06,384 RECENTLY DEVELOPED AND 4444 02:55:06,384 --> 02:55:08,486 CHARACTERIZED IS THE 4445 02:55:08,486 --> 02:55:09,887 FECAL-INDUCED PERITONITIS MODEL, 4446 02:55:09,887 --> 02:55:12,523 WHICH IS A POLYMICROBIAL MODEL 4447 02:55:12,523 --> 02:55:18,196 OF ABDOMINAL SEPSIS. 4448 02:55:18,196 --> 02:55:19,397 SO THERE ARE SEVERAL ADVANTAGES 4449 02:55:19,397 --> 02:55:22,266 OF THIS MODEL. 4450 02:55:22,266 --> 02:55:25,103 THE FIRST IS THAT THE INOCULUM 4451 02:55:25,103 --> 02:55:27,071 CAN BE STANDARDIZED, SO WE 4452 02:55:27,071 --> 02:55:28,606 HARVEST CECAL CONTENT FROM 4453 02:55:28,606 --> 02:55:29,073 MULTIPLE RATS. 4454 02:55:29,073 --> 02:55:30,575 THE REASON WE CHOOSE RATS IS 4455 02:55:30,575 --> 02:55:31,876 THAT THEY'RE MUCH LARGER, SO 4456 02:55:31,876 --> 02:55:34,545 THEY JUST HAVE MORE FECAL 4457 02:55:34,545 --> 02:55:36,214 CONTENT THAT WE CAN HARVEST, AND 4458 02:55:36,214 --> 02:55:41,886 WE FREEZE THEM IN BATCHES UP TO 4459 02:55:41,886 --> 02:55:44,188 2,000 -- AT A TIME THAT CAN BE 4460 02:55:44,188 --> 02:55:45,089 SHARED AMONGST DIFFERENT SITES. 4461 02:55:45,089 --> 02:55:46,524 THE TECHNIQUE IS VERY SIMPLE. 4462 02:55:46,524 --> 02:55:49,727 IT INVOLVES IP INJECTION, AND AS 4463 02:55:49,727 --> 02:55:55,299 KANDACE MENTIONED IN HE HURDLE,, 4464 02:55:55,299 --> 02:55:56,968 YOU CAN EASILY ALTER DISEASE 4465 02:55:56,968 --> 02:55:59,570 SEVERITY BY CHANGINGS THE DOSE 4466 02:55:59,570 --> 02:56:03,307 OF THE SLURRY YOU INJECT. 4467 02:56:03,307 --> 02:56:04,742 WE INCLUDE CLINICALLY RELEVANT 4468 02:56:04,742 --> 02:56:06,444 TREATMENTS CLINKING ANTIBIOTICS 4469 02:56:06,444 --> 02:56:09,781 AS WELL AS FLUID RESUSCITATION. 4470 02:56:09,781 --> 02:56:12,183 WE ALSO STANDARDIZE SCORING 4471 02:56:12,183 --> 02:56:15,453 SYSTEM, BECAUSE IN CANADA, AT 4472 02:56:15,453 --> 02:56:16,554 LEAST, WE AREN'T ALLOWED TO HAVE 4473 02:56:16,554 --> 02:56:17,889 DEATH AS AN END POINT, SO WE 4474 02:56:17,889 --> 02:56:20,625 NEED TO HAVE SURROGATE MARKERS 4475 02:56:20,625 --> 02:56:22,160 FOR HUMANE END POINTS, AND THIS 4476 02:56:22,160 --> 02:56:26,197 IS RELATED TO COMPONENTS OF THE 4477 02:56:26,197 --> 02:56:28,733 SEPSIS SCORE SUCH AS POSTURED 4478 02:56:28,733 --> 02:56:30,168 ACTIVITY, RESPIRATION QUALITY, 4479 02:56:30,168 --> 02:56:35,840 RUFFLED FUR AND RESPONSIVENESS. 4480 02:56:35,840 --> 02:56:37,008 FOR ANYONE WHO IS INTERESTED, WE 4481 02:56:37,008 --> 02:56:38,810 DO HAVE VIDEO RESOURCES RELATED 4482 02:56:38,810 --> 02:56:41,546 TO THIS MODEL, AND ALSO HOW 4483 02:56:41,546 --> 02:56:46,484 DIFFERENT ORGANS I AND BLOOD ARE 4484 02:56:46,484 --> 02:56:46,818 COLLECTED. 4485 02:56:46,818 --> 02:56:50,755 SO USING THIS MODEL, WE HAD THE 4486 02:56:50,755 --> 02:56:52,423 OPPORTUNITY TO LOOK AT THE DATA 4487 02:56:52,423 --> 02:56:54,725 THAT HAS EMERGED FROM THE 4488 02:56:54,725 --> 02:56:58,729 CLINICAL RESEARCHERS TO BRING IT 4489 02:56:58,729 --> 02:57:01,833 BACK INTO THE LAB TO BETTER 4490 02:57:01,833 --> 02:57:02,633 UNDERSTAND, FOR EXAMPLE, IF 4491 02:57:02,633 --> 02:57:05,236 THERE IS AN OPTIMAL DOSE AND 4492 02:57:05,236 --> 02:57:07,105 TIME TO ADMINISTER HEPARIN. 4493 02:57:07,105 --> 02:57:09,974 SO IN THIS MODEL, WE KNOW WHEN 4494 02:57:09,974 --> 02:57:15,313 SEPSIS IS INITIATED, BY THE TIME 4495 02:57:15,313 --> 02:57:17,181 AT WHICH THE FECAL SLURRY IS 4496 02:57:17,181 --> 02:57:17,648 INJECTED. 4497 02:57:17,648 --> 02:57:20,251 WE CAN THEN INJECT THE THERAPY 4498 02:57:20,251 --> 02:57:22,120 OF CHOICE N THIS CASE, I'M USING 4499 02:57:22,120 --> 02:57:23,988 HEPARIN AS AN EXAMPLE, AT 4500 02:57:23,988 --> 02:57:25,857 DIFFERENT TIMES AND AT DIFFERENT 4501 02:57:25,857 --> 02:57:26,524 DOSES. 4502 02:57:26,524 --> 02:57:29,927 THE END POINT WOULD BE 72 HOUR 4503 02:57:29,927 --> 02:57:31,562 SURVIVAL, AT WHICH TIME WE CAN 4504 02:57:31,562 --> 02:57:35,066 HARVEST THE O ORGANS, WE CAN 4505 02:57:35,066 --> 02:57:36,234 ANALYZE BIOMARKERS IN THE PLASMA 4506 02:57:36,234 --> 02:57:38,603 AND WE CAN LOOK AT BACTERIAL 4507 02:57:38,603 --> 02:57:44,041 BUILDS. 4508 02:57:44,041 --> 02:57:48,679 SO MOVING ON TO NOVEL THERAPIES, 4509 02:57:48,679 --> 02:57:51,949 A DECADE AGO, WE WERE LOOKING AT 4510 02:57:51,949 --> 02:57:53,885 BLOOD SAMPLES FROM ICU PATIENTS 4511 02:57:53,885 --> 02:57:55,686 WITH SEPSIS, AND WE MADE THE 4512 02:57:55,686 --> 02:57:57,221 OBSERVATION THAT THE SAMPLES 4513 02:57:57,221 --> 02:57:59,524 CONTAIN VERY HIGH LEVELS OF 4514 02:57:59,524 --> 02:58:03,027 EXTRACELLULAR DNA, AND WE'VE 4515 02:58:03,027 --> 02:58:04,028 IDENTIFIED THAT NEUTROPHILS ARE 4516 02:58:04,028 --> 02:58:08,499 THE MAJOR SOURCE OF THE 4517 02:58:08,499 --> 02:58:09,167 EXTRACELLULAR DNA. 4518 02:58:09,167 --> 02:58:15,940 THEY ARE RELEASED IN THE PROCESS 4519 02:58:15,940 --> 02:58:21,979 OF -- FACTOR 12 AND 11 DEPENDENT 4520 02:58:21,979 --> 02:58:22,413 MECHANISMS. 4521 02:58:22,413 --> 02:58:24,282 IT ALSO CHANGES THE MORPHOLOGY 4522 02:58:24,282 --> 02:58:27,785 OF THE BLOOD CLOT AND IT 4523 02:58:27,785 --> 02:58:29,453 PREVENTS CLOT BREAK DOWN BY 4524 02:58:29,453 --> 02:58:34,458 INHIBITING PLASMA -- SO WE 4525 02:58:34,458 --> 02:58:43,568 HYPOTHESIZED THAT PERHAPS WE'RES 4526 02:58:43,568 --> 02:58:46,037 RECOMBINANT DNASE1 -- PART OF 4527 02:58:46,037 --> 02:58:49,707 THE RATIONALE IS THAT IN ANIMAL 4528 02:58:49,707 --> 02:58:50,808 MODELS, ADMINISTRATION OF THIS 4529 02:58:50,808 --> 02:58:53,144 ENZYME REDUCES ORGAN DAMAGE AND 4530 02:58:53,144 --> 02:58:57,048 IMPROVES OUTCOME IN SEPTIC MICE. 4531 02:58:57,048 --> 02:58:59,617 IN PATIENTS, HIGH LEVELS OF DNA 4532 02:58:59,617 --> 02:59:01,986 PREDICTS POOR OUTCOME. 4533 02:59:01,986 --> 02:59:03,854 AND THERE'S ALSO ACQUIRED 4534 02:59:03,854 --> 02:59:08,359 DEFICIENCY OF ENDOGENOUS 4535 02:59:08,359 --> 02:59:09,560 DNASE1 IN ICU PATIENTS. 4536 02:59:09,560 --> 02:59:12,730 SO WE HAVE INITIATED A PHASE ONE 4537 02:59:12,730 --> 02:59:14,966 SAFETY AND FEASIBILITY STUDY TO 4538 02:59:14,966 --> 02:59:17,168 LOOK AT INTRAVENOUS D NAIS ONE 4539 02:59:17,168 --> 02:59:18,336 FOR THE TREATMENT OF PATIENTS 4540 02:59:18,336 --> 02:59:24,375 WITH SEPSIS. 4541 02:59:24,375 --> 02:59:27,144 IT'S A PHASE ONE LABELED DOSE 4542 02:59:27,144 --> 02:59:27,778 ESCALATION SAFETY AND 4543 02:59:27,778 --> 02:59:28,679 FEASIBILITY STUDY. 4544 02:59:28,679 --> 02:59:33,050 THE INTERVENTION IS INTRAVENOUS 4545 02:59:33,050 --> 02:59:35,052 DNASE 1 FOR 2 DOSES FOR EITHER 4546 02:59:35,052 --> 02:59:38,623 THREE DAYS OR SEVEN DAYS. 4547 02:59:38,623 --> 02:59:40,291 I JUST ALSO WANT TO MENTION THAT 4548 02:59:40,291 --> 02:59:43,461 THERE IS ANOTHER PHASE 4549 02:59:43,461 --> 02:59:45,863 1 CLINICAL STUDY LOOKING AT A 4550 02:59:45,863 --> 02:59:55,373 VARIANT OF DNASE 1 -- 4551 02:59:55,373 --> 02:59:56,974 COVID-19-RELATED SEPSIS. 4552 02:59:56,974 --> 03:00:00,678 SO FINALLY, CHOICE OF 4553 03:00:00,678 --> 03:00:01,912 POPULATION. 4554 03:00:01,912 --> 03:00:04,682 SO WILL ONE SIZE FIT ALL IN THE 4555 03:00:04,682 --> 03:00:05,449 TREATMENT OF SEPSIS? 4556 03:00:05,449 --> 03:00:09,387 THIS IS A NICE REVIEW BY STANSKI 4557 03:00:09,387 --> 03:00:11,689 AND WONG WHICH SUGGEST THAT 4558 03:00:11,689 --> 03:00:13,691 PROGNOSTIC ENRICHMENT AS WELL AS 4559 03:00:13,691 --> 03:00:19,030 PREDICTIVE ENRICHMENT MAY HELP 4560 03:00:19,030 --> 03:00:20,665 TO -- THE PATIENTS ARE 4561 03:00:20,665 --> 03:00:22,133 STRATIFIED BASED ON MORTALITY 4562 03:00:22,133 --> 03:00:22,733 RISK. 4563 03:00:22,733 --> 03:00:24,368 IN PREDICTIVE ENRICHMENT, 4564 03:00:24,368 --> 03:00:27,204 THEY'RE STRATIFIED BASED ON 4565 03:00:27,204 --> 03:00:30,641 BIOLOGICAL PATHWAYS THAT MAY BE 4566 03:00:30,641 --> 03:00:31,876 TARGETED THROUGH SPECIFIC 4567 03:00:31,876 --> 03:00:36,547 INTERVENTIONS. 4568 03:00:36,547 --> 03:00:38,082 SO WE CONDUCTED A LARGE 4569 03:00:38,082 --> 03:00:43,921 MULTICENTER STUDY TO LACK LOOKT 4570 03:00:43,921 --> 03:00:44,588 VARIATIONS BETWEEN INDIVIDUAL 4571 03:00:44,588 --> 03:00:47,725 PATIENTS WITH SEPSIS. 4572 03:00:47,725 --> 03:00:50,828 WE USED A COMBINATION OF ROUTINE 4573 03:00:50,828 --> 03:00:53,230 LABORATORY PARAMETERS SUCH AS 4574 03:00:53,230 --> 03:00:56,500 LACTATE PLATELET COUNT, 4575 03:00:56,500 --> 03:00:57,735 CREATINE, AS WELL AS CELL-FREE 4576 03:00:57,735 --> 03:01:00,037 DNA AND PROTEIN C. 4577 03:01:00,037 --> 03:01:02,673 WHAT WE FOUND IS THAT THERE ARE 4578 03:01:02,673 --> 03:01:04,175 MORTALITY RISK PROFILES THAT ARE 4579 03:01:04,175 --> 03:01:06,177 UNIQUE TO EACH PATIENT, AND THIS 4580 03:01:06,177 --> 03:01:09,046 JUST HIGHLIGHTS THAT, FOR 4581 03:01:09,046 --> 03:01:10,781 EXAMPLE, IN PATIENTS WITH HIGH 4582 03:01:10,781 --> 03:01:15,953 LEVELS OF CIRCULATING DNA, 4583 03:01:15,953 --> 03:01:17,588 PERHAPS DNASE ONE THERAPY IS 4584 03:01:17,588 --> 03:01:18,189 APPROPRIATE. 4585 03:01:18,189 --> 03:01:20,558 IN PATIENTS WITH REDUCED LEVELS 4586 03:01:20,558 --> 03:01:22,693 OF ANTICOAGULANTS, PERHAPS 4587 03:01:22,693 --> 03:01:23,761 HEPARIN THERAPY MAY BE 4588 03:01:23,761 --> 03:01:25,629 BENEFICIAL. 4589 03:01:25,629 --> 03:01:27,698 SO THIS IS JUST AN EXAMPLE OF 4590 03:01:27,698 --> 03:01:29,333 HOW A TARGETED APPROACH MIGHT 4591 03:01:29,333 --> 03:01:32,536 LOOK LIKE IN FUTURE CLINICAL 4592 03:01:32,536 --> 03:01:32,770 TRIALS. 4593 03:01:32,770 --> 03:01:34,004 SO THERE WOULD BE A POINT OF 4594 03:01:34,004 --> 03:01:36,040 CARE RISK ASSESSMENT TOOL, IN 4595 03:01:36,040 --> 03:01:38,909 THIS CASE, I'M USING THE EXAMPLE 4596 03:01:38,909 --> 03:01:43,080 OF THE ROUTINE LABORATORY 4597 03:01:43,080 --> 03:01:44,915 INVESTIGATIONAL PARAMETERS THAT 4598 03:01:44,915 --> 03:01:46,584 COULD IDENTIFY WHICH INDICATOR 4599 03:01:46,584 --> 03:01:47,918 CONTRIBUTE THE MOST TO MORTALITY 4600 03:01:47,918 --> 03:01:48,786 RISK. 4601 03:01:48,786 --> 03:01:51,856 THE APPLICATIONS MAY THEN BE 4602 03:01:51,856 --> 03:01:52,890 TARGETED THERAPY AS WELL AS 4603 03:01:52,890 --> 03:01:53,624 MONITORING RESPONSE TO 4604 03:01:53,624 --> 03:01:57,561 TREATMENT. 4605 03:01:57,561 --> 03:01:59,530 SO JUST WANT TO SUMMARIZE THAT 4606 03:01:59,530 --> 03:02:01,399 THERE ARE STRATEGIES TO OVERCOME 4607 03:02:01,399 --> 03:02:02,500 BARRIERS IN CLINICAL TRIALS IN 4608 03:02:02,500 --> 03:02:02,733 SEPSIS. 4609 03:02:02,733 --> 03:02:04,268 THIS IS RELATED TO THE TIMING OR 4610 03:02:04,268 --> 03:02:06,470 DOSE OF THERAPY, THE TYPE OF 4611 03:02:06,470 --> 03:02:07,805 INTERVENTION, AND HETEROGENEITY 4612 03:02:07,805 --> 03:02:11,776 IN THE POPULATION. 4613 03:02:11,776 --> 03:02:12,943 THE ULTIMATE GOAL IS TO SELECT 4614 03:02:12,943 --> 03:02:14,044 THE RIGHT TREATMENT AT THE RIGHT 4615 03:02:14,044 --> 03:02:15,579 TIME AND AT THE OPTIMAL DOSE FOR 4616 03:02:15,579 --> 03:02:18,649 THE RIGHT PATIENT. 4617 03:02:18,649 --> 03:02:20,985 I'D JUST LIKE TO THANK MY LAB 4618 03:02:20,985 --> 03:02:22,386 MEMBERS, AS WELL AS MANY 4619 03:02:22,386 --> 03:02:23,754 COLLABORATORS WITHIN THE 4620 03:02:23,754 --> 03:02:26,557 CRITICAL CARE FIELD, AS WELL AS 4621 03:02:26,557 --> 03:02:27,992 OUR COLLEAGUES AT UNIVERSITY OF 4622 03:02:27,992 --> 03:02:28,426 MONTREAL. 4623 03:02:28,426 --> 03:02:35,566 THANK YOU. 4624 03:02:35,566 --> 03:02:36,967 >> VERY NICE, VERY NICE TALK. 4625 03:02:36,967 --> 03:02:37,635 THANK YOU VERY MUCH. 4626 03:02:37,635 --> 03:02:42,673 I THINK WE SHOULD START THE 4627 03:02:42,673 --> 03:02:43,374 DISCUSSION PANEL. 4628 03:02:43,374 --> 03:02:47,077 WE HAVE LIKE -- HOW MUCH TIME DO 4629 03:02:47,077 --> 03:02:51,882 WE HAVE? 4630 03:02:51,882 --> 03:02:52,183 SAY -- 1:45? 4631 03:02:52,183 --> 03:02:53,284 >> ABOUT 21 MINUTES. 4632 03:02:53,284 --> 03:02:55,119 >> OKAY. 4633 03:02:55,119 --> 03:02:57,321 >> YEAH, UNTIL 1:45. 4634 03:02:57,321 --> 03:03:01,358 >> I THINK WE CAN BRING 4635 03:03:01,358 --> 03:03:04,228 EVERYBODY ON THE SPEAKERS ON THE 4636 03:03:04,228 --> 03:03:11,936 PANEL. 4637 03:03:11,936 --> 03:03:13,137 I CAN START WITH THE DISCUSSION 4638 03:03:13,137 --> 03:03:13,604 ACTUALLY. 4639 03:03:13,604 --> 03:03:15,906 OKAY, I THINK THERE IS A 4640 03:03:15,906 --> 03:03:16,173 QUESTION. 4641 03:03:16,173 --> 03:03:17,041 PLEASE GO AHEAD. 4642 03:03:17,041 --> 03:03:19,009 >> YES, THANK YOU. 4643 03:03:19,009 --> 03:03:20,311 THESE WERE GREAT PRESENTATIONS. 4644 03:03:20,311 --> 03:03:23,514 I HAD ACTUALLY TWO QUESTIONS. 4645 03:03:23,514 --> 03:03:26,484 REGARDING THE PAD 4 EXPERIMENTS, 4646 03:03:26,484 --> 03:03:29,753 WITH THE CECAL SLURRY THAT WERE 4647 03:03:29,753 --> 03:03:32,823 DONE AT CHOP. 4648 03:03:32,823 --> 03:03:36,327 SO DID YOU LOOK AT CLINICAL 4649 03:03:36,327 --> 03:03:38,195 SCORES LIKE JUST NOW WE HEARD 4650 03:03:38,195 --> 03:03:39,864 ABOUT THE SCORING SYSTEM THAT 4651 03:03:39,864 --> 03:03:43,601 THEY'RE USING IN CANADA, THERE'S 4652 03:03:43,601 --> 03:03:46,570 THE SHROOM ET AL. CLINICAL 4653 03:03:46,570 --> 03:03:48,172 SCORES FOR MICE SINCE 2014. 4654 03:03:48,172 --> 03:03:53,811 HAVE YOU LOOKED INTO HOW THEY 4655 03:03:53,811 --> 03:03:54,979 DID CLINICALLY? 4656 03:03:54,979 --> 03:03:56,413 AND ALSO FROM THE LAST TALK, I 4657 03:03:56,413 --> 03:03:57,781 WAS WONDERING, SINCE WE TALKED 4658 03:03:57,781 --> 03:04:03,888 ABOUT THE I MAWN RESPONSE AND ID 4659 03:04:03,888 --> 03:04:05,923 HOW -- WE KNOW THERE'S AN 4660 03:04:05,923 --> 03:04:07,424 IMBALANCE OF HYPERIMMUNE AND 4661 03:04:07,424 --> 03:04:10,060 IMMUNE PARALYSIS IN SEPSIS. 4662 03:04:10,060 --> 03:04:15,232 HAVE WE LOOKED AT OTHER THAN THE 4663 03:04:15,232 --> 03:04:16,534 IMMUNE RESPONSE LIKE METABOLIC 4664 03:04:16,534 --> 03:04:17,368 CHANGES, FOR EXAMPLE, THAT CAN 4665 03:04:17,368 --> 03:04:20,170 DRIVE OR CHANGE THE IMMUNE 4666 03:04:20,170 --> 03:04:21,839 RESPONSE IN SEPSIS, ARE YOU 4667 03:04:21,839 --> 03:04:23,073 AWARE OR HAVE YOU DONE ANY 4668 03:04:23,073 --> 03:04:25,376 RELEVANT STUDIES WITH 4669 03:04:25,376 --> 03:04:28,145 IMMUNOTHROMBOSIS? 4670 03:04:28,145 --> 03:04:30,014 >> WELL, I CAN ANSWER QUICKLY TO 4671 03:04:30,014 --> 03:04:32,550 START AND THEN PASS THE BATON TO 4672 03:04:32,550 --> 03:04:33,984 DR. LIAW, BUT WE DID DO A 4673 03:04:33,984 --> 03:04:34,652 CLINICAL SEPSIS SCORE. 4674 03:04:34,652 --> 03:04:39,890 WE USED THE MEAN SEPSIS SCORE 4675 03:04:39,890 --> 03:04:41,659 WHICH TAKES INTO ACCOUNT REGS 4676 03:04:41,659 --> 03:04:44,228 PIER TRI RATE, EYE OPENING, SKIN 4677 03:04:44,228 --> 03:04:46,597 TURGOR AND MOVEMENT, AND IT PUTS 4678 03:04:46,597 --> 03:04:47,498 ALL THOSE TOGETHER AND YOU KIND 4679 03:04:47,498 --> 03:04:50,267 OF GET A FINAL CLINICAL SCORE, 4680 03:04:50,267 --> 03:04:51,769 SO WE USE THAT TO ASSESS OUR 4681 03:04:51,769 --> 03:04:52,436 ANIMALS CLINICALLY. 4682 03:04:52,436 --> 03:04:54,438 I WILL SAY FOR OUR -- PROTOCOL, 4683 03:04:54,438 --> 03:04:56,540 IT'S WRITTEN IN THERE THAT WHEN 4684 03:04:56,540 --> 03:04:58,375 ANIMALS EXCEED AN MSS OF 14, 4685 03:04:58,375 --> 03:04:59,510 THEY HAVE TO BE EUTHANIZED. 4686 03:04:59,510 --> 03:05:02,913 SO WE'RE ALSO IN THE BOAT OF 4687 03:05:02,913 --> 03:05:05,215 HAVING TO UTE NIEZ OUR ANIMALS 4688 03:05:05,215 --> 03:05:06,550 BEFORE THEY EXCEED THAT LEVEL, 4689 03:05:06,550 --> 03:05:08,018 SO THAT IS A COMOANT OF THOSE 4690 03:05:08,018 --> 03:05:10,387 STUDIES. 4691 03:05:10,387 --> 03:05:11,755 A COMPONENT OF THOSE STUDIES. 4692 03:05:11,755 --> 03:05:13,057 >> COULD YOU REPEAT THE SECOND 4693 03:05:13,057 --> 03:05:14,625 HALF OF YOUR QUESTION? 4694 03:05:14,625 --> 03:05:15,559 SORRY, I JUST WANT TO -- 4695 03:05:15,559 --> 03:05:18,429 >> YES, IF THERE WERE -- IF WE 4696 03:05:18,429 --> 03:05:20,798 LOOK AT OTHER PARAMETERS OTHER 4697 03:05:20,798 --> 03:05:22,666 THAN THE IMMUNE RESPONSE, AND I 4698 03:05:22,666 --> 03:05:28,005 KNOW YOU TALKED ABOUT THE USE OF 4699 03:05:28,005 --> 03:05:29,373 HEPARIN, BUT WERE THERE OTHER 4700 03:05:29,373 --> 03:05:31,008 COMPONENTS LIKE THE ROLE OF 4701 03:05:31,008 --> 03:05:33,644 METABOLISM, FOR EXAMPLE, IN 4702 03:05:33,644 --> 03:05:34,278 THOSE EXPERIMENTS AND HOW THAT 4703 03:05:34,278 --> 03:05:36,814 CHANGES THE IMMUNE RESPONSE, AND 4704 03:05:36,814 --> 03:05:40,551 IF THERE IS ANY CORRELATION WITH 4705 03:05:40,551 --> 03:05:42,853 CHANGING IMMUNOTHROMBOSIS AND 4706 03:05:42,853 --> 03:05:44,555 WHETHER HEPARIN HAS ANY -- IS 4707 03:05:44,555 --> 03:05:45,956 THERE ANY INDICATION THAT 4708 03:05:45,956 --> 03:05:46,991 HEPARIN CHANGES ANY OF THAT AS 4709 03:05:46,991 --> 03:05:47,958 WELL? 4710 03:05:47,958 --> 03:05:50,894 >> THERE ARE IN VITRO STUDIES 4711 03:05:50,894 --> 03:05:52,129 WHICH SHOULD SUGGEST THAT 4712 03:05:52,129 --> 03:05:54,865 HEPARIN CAN ACTUALLY CHANGE THE 4713 03:05:54,865 --> 03:05:58,335 GENE EXPRESSION PROFILE OF 4714 03:05:58,335 --> 03:05:58,702 MACROPHAGE. 4715 03:05:58,702 --> 03:06:01,672 WE HAVE STARTED TO LOOK AT THE 4716 03:06:01,672 --> 03:06:03,540 EPIGENETICS OF SEPSIS TO SEE IF 4717 03:06:03,540 --> 03:06:04,975 THERAPY SUCH AS HEPARIN THAT 4718 03:06:04,975 --> 03:06:07,945 HAVE THE POTENTIAL TO CHANGE 4719 03:06:07,945 --> 03:06:10,714 GENE EXPRESSION, IF THAT 4720 03:06:10,714 --> 03:06:12,449 MODIFIES THE EPIGENETIC 4721 03:06:12,449 --> 03:06:14,551 LANDSCAPE OF THE MICE DURING THE 4722 03:06:14,551 --> 03:06:16,053 PROGRESSION OF SEPSIS. 4723 03:06:16,053 --> 03:06:20,057 IN TERMS OF THE EFFECTS OF 4724 03:06:20,057 --> 03:06:23,661 ALTERATIONS IN METABOLISM, WE 4725 03:06:23,661 --> 03:06:24,762 HAVEN'T SPECIFICALLY LOOKED AT 4726 03:06:24,762 --> 03:06:27,731 THAT, AND I THINK THAT'S AN AREA 4727 03:06:27,731 --> 03:06:29,700 THAT IS DEFINITELY WORTH 4728 03:06:29,700 --> 03:06:29,967 EXPLORING. 4729 03:06:29,967 --> 03:06:32,036 THE OTHER LIMITATION OF USING 4730 03:06:32,036 --> 03:06:33,370 ANIMAL MODELS IS THAT WE OFTEN 4731 03:06:33,370 --> 03:06:35,472 USE HEALTHY YOUNG MICE, AND OF 4732 03:06:35,472 --> 03:06:37,307 COURSE IN SEPSIS, THE PATIENTS 4733 03:06:37,307 --> 03:06:39,276 ARE OLDER AND WE HEARD IN THE 4734 03:06:39,276 --> 03:06:40,411 FIRST SESSION THAT THERE ARE 4735 03:06:40,411 --> 03:06:41,645 CO-MORBID ITS. 4736 03:06:41,645 --> 03:06:44,148 SO THERE ARE OPPORTUNITIES TO 4737 03:06:44,148 --> 03:06:46,984 LOOK AT THE IMPACT OF AGING IN 4738 03:06:46,984 --> 03:06:50,287 THESE MODELS, AS WELL AS OTHER 4739 03:06:50,287 --> 03:06:50,988 COMORBIDITIES. 4740 03:06:50,988 --> 03:06:53,957 WE PUBLISHED A SMALL STUDY WHERE 4741 03:06:53,957 --> 03:06:59,229 WE LOOKED AT 12 MONTH OLD MICE, 4742 03:06:59,229 --> 03:07:00,631 WHICH I GUESS WOULD BE 4743 03:07:00,631 --> 03:07:02,933 CONSIDERED ELDERLY. 4744 03:07:02,933 --> 03:07:03,901 THEY'RE AROUND 65 HUMAN YEARS, 4745 03:07:03,901 --> 03:07:07,071 AND THERE IS A SIGNIFICANT 4746 03:07:07,071 --> 03:07:09,239 DIFFERENCE IN THE IMMUNE 4747 03:07:09,239 --> 03:07:11,075 RESPONSE WHICH REFLECTS THEIR 4748 03:07:11,075 --> 03:07:13,510 POOR SURVIVAL COMPARED TO YOUNG 4749 03:07:13,510 --> 03:07:14,511 HEALTHY MICE. 4750 03:07:14,511 --> 03:07:19,016 WE'RE ALSO LOOKING AT DIABETES 4751 03:07:19,016 --> 03:07:21,085 MODELS TO SEE HOW DIABETES 4752 03:07:21,085 --> 03:07:22,720 IMPACTS OUTCOME IN THE CONTEXT 4753 03:07:22,720 --> 03:07:26,824 OF SEPSIS AS WELL. 4754 03:07:26,824 --> 03:07:27,891 >> THANK YOU. 4755 03:07:27,891 --> 03:07:29,660 >> COULD I ASK A QUESTION FOR 4756 03:07:29,660 --> 03:07:30,661 PATRICIA. 4757 03:07:30,661 --> 03:07:33,530 IN TERMS OF THE SORT OF THERAPY 4758 03:07:33,530 --> 03:07:36,033 DISMANTLING THE NETS, NUMBER ONE 4759 03:07:36,033 --> 03:07:38,569 IS, WHEN IS THE TIMING OF THE 4760 03:07:38,569 --> 03:07:39,937 DNASE ADMINISTRATION, AND NUMBER 4761 03:07:39,937 --> 03:07:41,238 TWO, ARE YOU CONCERNED THAT 4762 03:07:41,238 --> 03:07:42,973 DISMANTLING THE NETS MAY 4763 03:07:42,973 --> 03:07:44,141 ACTUALLY RELEASE A LOT OF NET 4764 03:07:44,141 --> 03:07:46,210 FACTORS THAT COULD ACTUALLY 4765 03:07:46,210 --> 03:07:48,078 THEMSELVES EXACERBATE THE 4766 03:07:48,078 --> 03:07:48,612 DISEASE? 4767 03:07:48,612 --> 03:07:49,913 WHAT ARE YOUR VIEWS ON THAT? 4768 03:07:49,913 --> 03:07:52,049 >> WE'VE DONE A TIME COURSE 4769 03:07:52,049 --> 03:07:53,917 STUDY WHICH SHOWED THAT IF YOU 4770 03:07:53,917 --> 03:07:56,320 ADMINISTER DNASE VERY EARLY ON, 4771 03:07:56,320 --> 03:07:59,556 IT ACTUALLY WORSENS OUTCOME, 4772 03:07:59,556 --> 03:08:03,360 AND -- BECAUSE CONCEPTUALLY THAT 4773 03:08:03,360 --> 03:08:04,995 DOES MAKE SENSE BECAUSE YOU 4774 03:08:04,995 --> 03:08:06,897 COULD THINK OF THE NETS BEING 4775 03:08:06,897 --> 03:08:08,232 DISMANTLED WHICH CONTRIBUTES TO 4776 03:08:08,232 --> 03:08:09,199 BACTERIAL DISSEMINATION. 4777 03:08:09,199 --> 03:08:12,636 SO IN OUR MOUSE MODELS, IT'S 4778 03:08:12,636 --> 03:08:14,404 PROTECTIVE IN THE LATER STAGES 4779 03:08:14,404 --> 03:08:16,807 OF SEPSIS, MEANING WE ADMINISTER 4780 03:08:16,807 --> 03:08:20,344 IT, I THINK BEYOND EIGHT HOURS. 4781 03:08:20,344 --> 03:08:24,948 IN TERMS OF DISMANTLING NET 4782 03:08:24,948 --> 03:08:26,150 COMPONENTS, THE OBVIOUS ONE 4783 03:08:26,150 --> 03:08:28,152 WOULD BE EXTRACELLULAR HISTONES, 4784 03:08:28,152 --> 03:08:30,387 WHICH WERE CYTOTOXIC AND THEY 4785 03:08:30,387 --> 03:08:32,089 CAN ACTIVATE PLATELETS, WE'VE 4786 03:08:32,089 --> 03:08:34,992 DONE A COMBINATION THERAPY WITH 4787 03:08:34,992 --> 03:08:37,594 DNASE ENZYME AS WELL AS HEPARIN, 4788 03:08:37,594 --> 03:08:39,229 SO THE STRATEGY WAS THAT 4789 03:08:39,229 --> 03:08:40,564 HEPARIN, WHICH HAS THE ABILITY 4790 03:08:40,564 --> 03:08:45,002 TO NEUTRALIZE HISTONES, MAY BE 4791 03:08:45,002 --> 03:08:46,837 THAT COMBINATION WOULD ACTUALLY 4792 03:08:46,837 --> 03:08:48,705 BE SYNERGISTIC AND HAVE AN 4793 03:08:48,705 --> 03:08:49,339 ADDITIVE BENEFIT. 4794 03:08:49,339 --> 03:08:50,741 BUT IN THE MICE, WE ACTUALLY 4795 03:08:50,741 --> 03:08:52,276 DIDN'T SEE THAT. 4796 03:08:52,276 --> 03:08:55,245 IN THE ANIMAL -- IN THE HUMAN 4797 03:08:55,245 --> 03:08:56,480 CLINICAL TRIALS, THAT'S 4798 03:08:56,480 --> 03:08:57,815 DEFINITELY SOMETHING THAT WE DO 4799 03:08:57,815 --> 03:08:58,682 NEED TO CONSIDER. 4800 03:08:58,682 --> 03:09:01,652 SO THAT'S WHY WE'RE STARTING 4801 03:09:01,652 --> 03:09:05,522 WITH THE SAFETY STUDY, AND AT 4802 03:09:05,522 --> 03:09:10,194 EACH DOSE OF THE DNASE 1, 4803 03:09:10,194 --> 03:09:12,863 THERE'S A DATA SAFETY MONITORING 4804 03:09:12,863 --> 03:09:15,098 COMMITTEE THAT WILL ASSESS 4805 03:09:15,098 --> 03:09:16,600 WHETHER OR NOT IT IS SAFE TO 4806 03:09:16,600 --> 03:09:18,135 PROGRESS TO THE NEXT HIGHER DOSE 4807 03:09:18,135 --> 03:09:20,571 AND ALSO FOR LONGER LENGTH OF 4808 03:09:20,571 --> 03:09:20,771 TIME. 4809 03:09:20,771 --> 03:09:22,606 BUT NIGEL, THAT'S AN EXCELLENT 4810 03:09:22,606 --> 03:09:24,408 POINT BECAUSE THERE ARE SO MANY 4811 03:09:24,408 --> 03:09:28,078 PRO THROMBOTIC AMINO -- 4812 03:09:28,078 --> 03:09:28,846 PRO-INFLAMMATORY COMPONENTS IN 4813 03:09:28,846 --> 03:09:30,581 NETS AS WELL THAT COULD EASILY 4814 03:09:30,581 --> 03:09:31,081 BE RELEASE. 4815 03:09:31,081 --> 03:09:33,951 >> AND YOU'VE CHOSEN HEPARIN, 4816 03:09:33,951 --> 03:09:36,420 YOUR FAVORITE MOLECULE IS APC. 4817 03:09:36,420 --> 03:09:38,055 IS THAT OFF THE TABLE NOW, ARE 4818 03:09:38,055 --> 03:09:39,823 PEOPLE NOT INTERESTED IN APC? 4819 03:09:39,823 --> 03:09:41,291 BECAUSE IT OBVIOUSLY WAS A VERY 4820 03:09:41,291 --> 03:09:43,260 GOOD MOLECULE AS AN 4821 03:09:43,260 --> 03:09:44,261 ANTICOAGULANT. 4822 03:09:44,261 --> 03:09:46,330 IT'S ALSO CLEAVES AND 4823 03:09:46,330 --> 03:09:48,098 INACTIVATES THE HISTONES, SO WHY 4824 03:09:48,098 --> 03:09:51,501 THE CHOICE OF HEPARIN VERSUS 4825 03:09:51,501 --> 03:09:54,404 OTHER SORT OF ANTICOAGULANTS? 4826 03:09:54,404 --> 03:09:56,073 >> I STILL HAVE A BOTTLE OF 4827 03:09:56,073 --> 03:09:57,708 CLINICAL GRADE APC IN MY FRIDGE 4828 03:09:57,708 --> 03:09:58,876 AT HOME. 4829 03:09:58,876 --> 03:10:01,345 IT NEXT TO THE KETCHUP BOTTLE. 4830 03:10:01,345 --> 03:10:05,382 I'M NOT SURE IF I KNOW 4831 03:10:05,382 --> 03:10:06,049 ACTUALLY -- I THINK THE REASON 4832 03:10:06,049 --> 03:10:09,820 WE STARTED WITH HEPARIN, IT'S A 4833 03:10:09,820 --> 03:10:11,355 CLINICAL GRADE COMPOUND. 4834 03:10:11,355 --> 03:10:14,958 I DON'T KNOW IF CLINICAL GRADE 4835 03:10:14,958 --> 03:10:16,426 APC IS AVAILABLE. 4836 03:10:16,426 --> 03:10:17,828 THERE'S RESEARCH GRADE, BUT WE 4837 03:10:17,828 --> 03:10:19,596 HAVEN'T LOOKED AT THAT 4838 03:10:19,596 --> 03:10:20,364 CURRENTLY. 4839 03:10:20,364 --> 03:10:23,133 WE DO MEASURE PROTEIN C LEVELS 4840 03:10:23,133 --> 03:10:26,970 IN THESE MICE, AND AS YOU WOULD 4841 03:10:26,970 --> 03:10:28,939 EXPECT, THERE IS ACQUIRED 4842 03:10:28,939 --> 03:10:30,841 DEFICIENCY, SO CONSUMPTION OF 4843 03:10:30,841 --> 03:10:33,543 PROTEIN C WITHIN THE FIRST EIGHT 4844 03:10:33,543 --> 03:10:34,311 HOURS. 4845 03:10:34,311 --> 03:10:35,612 BUT DEFINITELY THAT'S SOMETHING 4846 03:10:35,612 --> 03:10:37,014 WE COULD INVESTIGATE AS WELL. 4847 03:10:37,014 --> 03:10:38,649 >> AND JUST A LAST QUESTION IS, 4848 03:10:38,649 --> 03:10:42,786 IS THE SOLUBLE THROMBOMOD LIPMON 4849 03:10:42,786 --> 03:10:43,954 WAS VERY FASCINATING TO ME WHEN 4850 03:10:43,954 --> 03:10:44,922 I STARTED LOOKING INTO THIS 4851 03:10:44,922 --> 03:10:46,690 BECAUSE I WANT WASN'T REALLY 4852 03:10:46,690 --> 03:10:47,591 SORT OF AWARE OF THAT BEING 4853 03:10:47,591 --> 03:10:48,125 USED. 4854 03:10:48,125 --> 03:10:49,459 THAT CLEARLY IS AN ACTIVATOR OF 4855 03:10:49,459 --> 03:10:50,761 THE PROTEIN C PATHWAY, AND 4856 03:10:50,761 --> 03:10:52,029 THAT'S HOW IT'S ACTING TO 4857 03:10:52,029 --> 03:10:53,764 BENEFIT AND REDUCE THE DIC. 4858 03:10:53,764 --> 03:11:00,871 WHAT ARE YOUR THOUGHT ON SOLUBLE 4859 03:11:00,871 --> 03:11:01,238 THROMBOMODULIN? 4860 03:11:01,238 --> 03:11:03,307 >> IN MICE WE HAVEN'T BEEN ABLE 4861 03:11:03,307 --> 03:11:04,841 TO CONSISTENTLY DEMONSTRATE THAT 4862 03:11:04,841 --> 03:11:09,112 THEY ACTUALLY WOULD GET DIC, AT 4863 03:11:09,112 --> 03:11:13,850 LEAST BASED ON THE ISTH DH 4864 03:11:13,850 --> 03:11:15,953 SCORES THAT MEASURES FIBRINOGEN 4865 03:11:15,953 --> 03:11:17,521 LEVELS, INR. 4866 03:11:17,521 --> 03:11:21,258 THE FIBRINOGEN LEVELS IN MICE, 4867 03:11:21,258 --> 03:11:27,397 UNLIKE IN HUMAN DIC, IN MICE THE 4868 03:11:27,397 --> 03:11:28,832 LEVELS DECREASE. 4869 03:11:28,832 --> 03:11:30,701 WE ALSO DON'T SEE THE SAME 4870 03:11:30,701 --> 03:11:33,103 REDUCTION IN PLATELETS AS YOU 4871 03:11:33,103 --> 03:11:34,705 WOULD SEE IN HUMAN DIC. 4872 03:11:34,705 --> 03:11:36,773 SO I JUST DON'T KNOW IF IT'S A 4873 03:11:36,773 --> 03:11:38,742 SPECIES THING OR MAYBE THERE 4874 03:11:38,742 --> 03:11:41,845 NEEDS TO BE A MODIFICATION OF 4875 03:11:41,845 --> 03:11:42,746 THE SCORE THAT WOULD BE 4876 03:11:42,746 --> 03:11:43,780 APPROPRIATE FOR MICE, BECAUSE 4877 03:11:43,780 --> 03:11:48,552 WHEN WE TRY TO USE THE HUMAN 4878 03:11:48,552 --> 03:11:52,756 SCOAR, WE SCORE, EVEN THOUGH THK 4879 03:11:52,756 --> 03:11:53,957 SEPTIC, THEY HAVE ALL THE 4880 03:11:53,957 --> 03:11:55,425 PHYSIOLOGICAL SIGNS AND THERE IS 4881 03:11:55,425 --> 03:11:57,627 MORTALITY, AT LEAST BASED ON THE 4882 03:11:57,627 --> 03:11:59,730 SCORE, THEY DON'T HAVE DIC, IF 4883 03:11:59,730 --> 03:12:00,263 THAT MAKES SENSE. 4884 03:12:00,263 --> 03:12:02,933 >> WHAT ABOUT D-DIMERSER? 4885 03:12:02,933 --> 03:12:06,003 WE ACTUALLY DON'T SEE D-DIMER. 4886 03:12:06,003 --> 03:12:08,372 I KNOW OTHERS HAVE SEEN D-DIMER 4887 03:12:08,372 --> 03:12:09,339 GO UP IN THEIR MODEL. 4888 03:12:09,339 --> 03:12:10,440 WE DON'T SEE IT. 4889 03:12:10,440 --> 03:12:12,409 HAVE YOU SEEN D-DIMERSER GO UP 4890 03:12:12,409 --> 03:12:13,243 IN YOUR MODEL? 4891 03:12:13,243 --> 03:12:14,678 >> NO, WE DON'T SEE IT ELEVATED 4892 03:12:14,678 --> 03:12:16,513 AN THAT'S THE OTHER DIFFERENCE 4893 03:12:16,513 --> 03:12:19,549 AS WELL. 4894 03:12:19,549 --> 03:12:27,090 TAT LEVELS ARE INCREASED BUT NOT 4895 03:12:27,090 --> 03:12:29,593 D-D IMER. 4896 03:12:29,593 --> 03:12:33,597 >> OKAY, I'LL GO. 4897 03:12:33,597 --> 03:12:36,466 SO I WAS QUITE FASCINATED BY THE 4898 03:12:36,466 --> 03:12:38,402 SIX PROGNOSTIC PARAMETERS THAT 4899 03:12:38,402 --> 03:12:40,871 PATRICIA YOU PRESENTED AND ALSO 4900 03:12:40,871 --> 03:12:43,173 THE SCORING SYSTEM, AND THAT 4901 03:12:43,173 --> 03:12:46,143 REMINDED ME OF A COUPLE OF 4902 03:12:46,143 --> 03:12:49,279 STUDIES FROM HARVARD AND TEMPLE 4903 03:12:49,279 --> 03:12:50,013 UNIVERSITIES WHERE THEY ARE 4904 03:12:50,013 --> 03:12:52,883 LOOKING AT NEUTROPHIL MIGRATION 4905 03:12:52,883 --> 03:12:54,251 PROFILES AS A PROGNOSTIC FACTOR, 4906 03:12:54,251 --> 03:12:56,853 AND IT HAS BEEN SHOWN THAT THE 4907 03:12:56,853 --> 03:12:58,522 NEUTROPHIL MIGRATION IMPAIRMENT 4908 03:12:58,522 --> 03:13:01,925 OCCURS AND IT CORRELATES WITH 4909 03:13:01,925 --> 03:13:03,160 THE SEVERITY OF SEPSIS. 4910 03:13:03,160 --> 03:13:04,461 SO WHAT ARE YOUR THOUGHTS ABOUT 4911 03:13:04,461 --> 03:13:06,329 IT AND DO YOU THINK THAT IT 4912 03:13:06,329 --> 03:13:09,766 COULD SERVE AS A PROGNOSTIC 4913 03:13:09,766 --> 03:13:11,535 FACTOR ONE DAY, AS A FUNCTION OF 4914 03:13:11,535 --> 03:13:14,171 RESPONSE OF IMMUNE CELLS? 4915 03:13:14,171 --> 03:13:16,440 >> YES, DEFINITELY, I THINK THE 4916 03:13:16,440 --> 03:13:18,708 REASON WE PICK THE SIX 4917 03:13:18,708 --> 03:13:22,646 INDICATORS IS THAT THESE WERE 4918 03:13:22,646 --> 03:13:25,215 INDICATORS THAT THE SITES COULD 4919 03:13:25,215 --> 03:13:27,951 EASILY MEASURE BECAUSE NOT ALL 4920 03:13:27,951 --> 03:13:31,354 OF THE SITES HAD RESEARCH LABS 4921 03:13:31,354 --> 03:13:33,423 ATTACHED TO THEM, SO I GUESS IF 4922 03:13:33,423 --> 03:13:35,992 YOU WANTED TO LOOK AT NEUTROPHIL 4923 03:13:35,992 --> 03:13:37,661 MIGRATION, I'M NOT SURE THE TIME 4924 03:13:37,661 --> 03:13:41,264 FRAME OF THAT, BUT IF IT 4925 03:13:41,264 --> 03:13:42,966 REQUIRES THE NEUTROPHILS TO BE 4926 03:13:42,966 --> 03:13:44,201 ISOLATED, MY SENSE IS THAT THAT 4927 03:13:44,201 --> 03:13:46,470 PROBABLY WOULD BE AN ASSAY THAT 4928 03:13:46,470 --> 03:13:48,438 WOULD REQUIRE SEVERAL HOURS 4929 03:13:48,438 --> 03:13:51,007 VERSUS THE POINT OF CARE DEVICE 4930 03:13:51,007 --> 03:13:53,176 WHERE THESE ROUTINE CLINICAL 4931 03:13:53,176 --> 03:13:55,479 PARAMETERS OR INDICATORS COULD 4932 03:13:55,479 --> 03:13:58,381 BE VERY EASILY MEASURED AT THE 4933 03:13:58,381 --> 03:13:58,615 BEDSIDE. 4934 03:13:58,615 --> 03:14:01,017 >> YEAH, I THINK I CAN ELABORATE 4935 03:14:01,017 --> 03:14:02,385 ON THAT A LITTLE BITMENT THEY 4936 03:14:02,385 --> 03:14:10,827 ARE USING THESE MICRO FLEW TICKC 4937 03:14:10,827 --> 03:14:11,795 CHIPS -- FINGERPRINT SO IT COULD 4938 03:14:11,795 --> 03:14:13,864 BE A POINT OF CARE ASSAY. 4939 03:14:13,864 --> 03:14:14,831 >> RIGHT. 4940 03:14:14,831 --> 03:14:17,134 AND I GUESS WOULD YOU NEED TO 4941 03:14:17,134 --> 03:14:18,502 JUST HAVE WHOLE BLOOD, THEN, 4942 03:14:18,502 --> 03:14:18,735 RIGHT? 4943 03:14:18,735 --> 03:14:19,970 YOU DON'T EVEN NEED TO PROCESS 4944 03:14:19,970 --> 03:14:20,237 IT. 4945 03:14:20,237 --> 03:14:20,670 >> YEAH. 4946 03:14:20,670 --> 03:14:23,540 >> THAT'S INTERESTING. 4947 03:14:23,540 --> 03:14:24,141 >> EVERYONE, THANKS. 4948 03:14:24,141 --> 03:14:25,475 I HAVE A FEW QUESTIONS FOR 4949 03:14:25,475 --> 03:14:26,910 EVERYONE ACTUALLY. 4950 03:14:26,910 --> 03:14:30,847 SO WHEN I TALK TO THIS 4951 03:14:30,847 --> 03:14:31,982 SPECIFICALLY, PATRICIA, WHEN I 4952 03:14:31,982 --> 03:14:33,416 TALK TO THESE CRITICAL CARE 4953 03:14:33,416 --> 03:14:35,385 SPECIALIST, THEY OFTEN -- THEY 4954 03:14:35,385 --> 03:14:39,222 TELL YOU THAT THE BIGGEST 4955 03:14:39,222 --> 03:14:40,690 TREATMENT -- SEPSIS PATIENT IS 4956 03:14:40,690 --> 03:14:42,893 IN ICU TO MAINTAIN GLUCOSE 4957 03:14:42,893 --> 03:14:47,130 LEVELS. 4958 03:14:47,130 --> 03:14:52,836 SO REGARDING THE QUESTION, IT 4959 03:14:52,836 --> 03:14:55,405 STRUCK ME THAT METABOLISM PLAYS 4960 03:14:55,405 --> 03:14:58,608 A ROLE THAT MAYBE HASN'T BEEN 4961 03:14:58,608 --> 03:14:59,576 INVESTIGATED. 4962 03:14:59,576 --> 03:15:02,078 SO IT A VERY TIGHTROPE YOU HAVE 4963 03:15:02,078 --> 03:15:04,347 TO MAINTAIN THE GLUCOSE LEVEL? 4964 03:15:04,347 --> 03:15:06,616 >> THE CHALLENGE WITH MICE IS 4965 03:15:06,616 --> 03:15:09,052 THAT UNLIKE IN HUMANS WHO 4966 03:15:09,052 --> 03:15:10,754 DEVELOP HYPERGLYCEMIA, IN MICE 4967 03:15:10,754 --> 03:15:11,955 IT ACTUALLY THE OPPOSITE. 4968 03:15:11,955 --> 03:15:14,791 SO WE SEE A RAPID DROP IN BLOOD 4969 03:15:14,791 --> 03:15:16,593 GLUCOSE WITHIN FOUR HOURS OF 4970 03:15:16,593 --> 03:15:20,096 INDUCING SEPSIS. 4971 03:15:20,096 --> 03:15:22,165 SO TRYING TO MAINTAIN BLOOD 4972 03:15:22,165 --> 03:15:24,701 GLUCOSE IN THE MICE, WE'VE GIVEN 4973 03:15:24,701 --> 03:15:28,638 IP INJECTIONS OF DEXTROSE, FOR 4974 03:15:28,638 --> 03:15:30,106 EXAMPLE, TO SEE IF THAT HELPS TO 4975 03:15:30,106 --> 03:15:31,641 IMPROVE SURVIVAL, BUT BECAUSE 4976 03:15:31,641 --> 03:15:34,544 IT'S THE OPPOSITE OF HUMANS, I'M 4977 03:15:34,544 --> 03:15:36,112 NOT REALLY SURE HOW WE WOULD 4978 03:15:36,112 --> 03:15:40,283 STUDY THAT, AND IN HUMANS, MAYBE 4979 03:15:40,283 --> 03:15:41,384 SOME OF THE CLINICIANS COULD 4980 03:15:41,384 --> 03:15:45,989 COMMENT, BUT I'M NOT AWARE OF 4981 03:15:45,989 --> 03:15:52,562 MAINTAINING TIGHT BLOOD GLUCOSE 4982 03:15:52,562 --> 03:15:54,397 IS SOMETHING THAT IS STANDARD OF 4983 03:15:54,397 --> 03:15:54,598 CARE. 4984 03:15:54,598 --> 03:15:55,899 >> I'M A PEDIATRICIAN SO THINGS 4985 03:15:55,899 --> 03:15:57,334 ARE DIFFERENT FOR US BECAUSE OUR 4986 03:15:57,334 --> 03:15:59,269 PATIENTS TEND TO BE HEALTHIER AT 4987 03:15:59,269 --> 03:16:00,370 BASELINE, BUT A LOT OF TIMES 4988 03:16:00,370 --> 03:16:01,771 THESE KIDS WILL END UP IN 4989 03:16:01,771 --> 03:16:03,173 STEROIDS, AND IN THAT CONTEXT 4990 03:16:03,173 --> 03:16:05,141 OFTEN, WE HAVE GLUCOSE CONTROL 4991 03:16:05,141 --> 03:16:06,209 BECOMING AN ISSUE, BUT AT LEAST 4992 03:16:06,209 --> 03:16:10,213 IN THE CONTEXT OF PEDIATRIC 4993 03:16:10,213 --> 03:16:13,283 SEPSIS OUTSIDE OF STEROID 4994 03:16:13,283 --> 03:16:14,150 TREATMENT, GLUCOSE CONTROL IS A 4995 03:16:14,150 --> 03:16:16,586 HUGE COMPONENT OF WHAT WE USE. 4996 03:16:16,586 --> 03:16:19,089 GRANTED I'M A HEMATOLOGIST, NOT 4997 03:16:19,089 --> 03:16:20,724 AN INTENSIVIST, BUT THAT'S BEEN 4998 03:16:20,724 --> 03:16:21,224 MY EXPERIENCE. 4999 03:16:21,224 --> 03:16:23,893 >> THANK YOU. 5000 03:16:23,893 --> 03:16:28,298 >> I HAVE ANOTHER QUESTION 5001 03:16:28,298 --> 03:16:29,299 REGARDING NETS. 5002 03:16:29,299 --> 03:16:30,700 SO DNASE HAS BEEN AROUND FOR A 5003 03:16:30,700 --> 03:16:33,436 WHILE, AND I KNOW -- IT ALSO 5004 03:16:33,436 --> 03:16:35,238 FDA-APPROVED FOR CYSTIC 5005 03:16:35,238 --> 03:16:37,440 FIBROSIS. 5006 03:16:37,440 --> 03:16:40,176 SO WHY NOT SOMETHING LIKE 5007 03:16:40,176 --> 03:16:42,912 NEUTROPHIL ELASTASE, WHICH HAS 5008 03:16:42,912 --> 03:16:46,182 SO MANY INHIBITORS AND 5009 03:16:46,182 --> 03:16:46,716 PREPARATION. 5010 03:16:46,716 --> 03:16:48,618 WHY HAS THAT NOT BEEN -- IS 5011 03:16:48,618 --> 03:16:50,320 THERE AN ISSUE WITH IT, OR 5012 03:16:50,320 --> 03:16:53,890 SOMETHING MORE THEIR 5013 03:16:53,890 --> 03:16:54,758 POUTICALLY -- ANTITRYPSIN. 5014 03:16:54,758 --> 03:16:56,393 IS THERE SOME INTEREST IN THAT 5015 03:16:56,393 --> 03:16:58,928 OR IT'S BEEN THERE ARE ISSUES 5016 03:16:58,928 --> 03:17:00,030 WITH TESTING SOMETHING LIKE THAT 5017 03:17:00,030 --> 03:17:00,630 IN PATIENTS? 5018 03:17:00,630 --> 03:17:04,901 OR AT LEAST IN MICE MODELS. 5019 03:17:04,901 --> 03:17:09,773 >> I THINK DANARIXIN AND -- ARE 5020 03:17:09,773 --> 03:17:13,710 USED IN THE TREAT M OF COPD. 5021 03:17:13,710 --> 03:17:17,981 I HAVEN'T SEEN THEM OUST USED 5022 03:17:17,981 --> 03:17:19,249 TYPICALLY IN THE TREATMENT OF 5023 03:17:19,249 --> 03:17:21,318 SEPSIS, BUT THAT CLASS OF 5024 03:17:21,318 --> 03:17:28,325 MOLECULES CERTAINLY DOES EXIST. 5025 03:17:28,325 --> 03:17:31,428 >> I HAVE ONE QUESTION FOR YOU, 5026 03:17:31,428 --> 03:17:32,095 KANDACE. 5027 03:17:32,095 --> 03:17:34,731 SO WHERE THIS PFO COMES, IS IT 5028 03:17:34,731 --> 03:17:37,500 PLATELET DERIVED, PLATELETS 5029 03:17:37,500 --> 03:17:39,469 RELEASE THAT OR IT'S IN THE 5030 03:17:39,469 --> 03:17:40,704 CIRCULATION OR IT COMES FROM THE 5031 03:17:40,704 --> 03:17:41,004 ENDOTHELIUM? 5032 03:17:41,004 --> 03:17:43,406 WHERE DO YOU THINK THIS 5033 03:17:43,406 --> 03:17:44,040 PF4 COMES FROM? 5034 03:17:44,040 --> 03:17:48,511 >> PLATELET FACTOR 4 IS MAINLY 5035 03:17:48,511 --> 03:17:51,047 MADE BY -- CARRIER SITES AND 5036 03:17:51,047 --> 03:17:52,415 LOADED INTO THE PLATELET ALPHA 5037 03:17:52,415 --> 03:17:53,183 GRANULES. 5038 03:17:53,183 --> 03:17:54,584 SO PLATELETS ARE GOING TO DO THE 5039 03:17:54,584 --> 03:17:56,152 BULK OF THE WORK OF SORT OF 5040 03:17:56,152 --> 03:17:57,287 MOVING PF4 AROUND THE 5041 03:17:57,287 --> 03:17:58,455 CIRCULATION. 5042 03:17:58,455 --> 03:17:59,389 ONE OF THE QUESTIONS IN THE CHAT 5043 03:17:59,389 --> 03:18:02,359 IS HEY, DOESN'T IT GET ELEVATED 5044 03:18:02,359 --> 03:18:04,794 IN THE PLASMA OF PATIENTS? 5045 03:18:04,794 --> 03:18:06,963 AND ABSOLUTELY, YOU GET PLATELET 5046 03:18:06,963 --> 03:18:07,964 ACTIVATION, YOU GET 5047 03:18:07,964 --> 03:18:08,465 DEGRANULATION. 5048 03:18:08,465 --> 03:18:09,799 I THINK THERE'S BEEN A FEW 5049 03:18:09,799 --> 03:18:11,301 STUDIES WHERE WE SEE THERE'S 5050 03:18:11,301 --> 03:18:14,571 ELEVATED PLATELET FACTOR 4 IN 5051 03:18:14,571 --> 03:18:15,872 BOTH MURINE AS WELL AS HUMAN 5052 03:18:15,872 --> 03:18:17,006 SEPSIS. 5053 03:18:17,006 --> 03:18:21,244 BUT PF4 IS A VERY PEER MISCUE US 5054 03:18:21,244 --> 03:18:22,412 MOLECULE IN THAT IT LOVES TO 5055 03:18:22,412 --> 03:18:23,613 BIND TO NEGATIVELY CHARGED 5056 03:18:23,613 --> 03:18:24,814 COMPOUNDS, SO IT DOESN'T STAY IN 5057 03:18:24,814 --> 03:18:25,815 THE CIRCULATION FOR ALL THAT 5058 03:18:25,815 --> 03:18:29,352 LONG BECAUSE IT WILL BIND TO 5059 03:18:29,352 --> 03:18:34,190 GLYCO -- GL ON TOP OF THE 5060 03:18:34,190 --> 03:18:36,459 ENDOTHELIUM OR ON TOP OF 5061 03:18:36,459 --> 03:18:37,026 CIRCULATING CELLS. 5062 03:18:37,026 --> 03:18:39,195 SO IF YOU WANT TO GET YOUR 5063 03:18:39,195 --> 03:18:41,164 HIGHEST LOCAL CONCENTRATIONS OF 5064 03:18:41,164 --> 03:18:42,899 PF4, I THINK THE BEST WAY TO DO 5065 03:18:42,899 --> 03:18:45,301 IT IS THROUGH KIND OF A 5066 03:18:45,301 --> 03:18:47,570 PLATELET, AND SO MY HYPOTHESIS 5067 03:18:47,570 --> 03:18:49,172 IS THAT NETS, SINCE THEY DO SUCH 5068 03:18:49,172 --> 03:18:50,607 A GREAT JOB OF BINDING 5069 03:18:50,607 --> 03:18:52,709 PLATELETS, THAT YOU PROBABLY -- 5070 03:18:52,709 --> 03:18:57,814 WHEN YOU'RE NOT SEVERELY 5071 03:18:57,814 --> 03:19:01,084 THROMBOCYTOPENIC, YOU GET A 5072 03:19:01,084 --> 03:19:02,619 DECENT DELIVERY OF PLATELET 5073 03:19:02,619 --> 03:19:02,886 FACTOR 4. 5074 03:19:02,886 --> 03:19:03,887 >> THERE'S A QUESTION IN THE 5075 03:19:03,887 --> 03:19:04,888 CHAT THAT I'LL TAKE. 5076 03:19:04,888 --> 03:19:06,322 IT'S SORT OF DIRECTED AT 5077 03:19:06,322 --> 03:19:07,957 PATRICIA BUT IT HAS TISSUE 5078 03:19:07,957 --> 03:19:09,159 FACTOR IN IT. 5079 03:19:09,159 --> 03:19:10,760 SO IT'S ASKING ABOUT WHETHER 5080 03:19:10,760 --> 03:19:13,830 DOES TISSUE FACTOR THAT'S 5081 03:19:13,830 --> 03:19:15,799 ALREADY ARRIVED FROM A VIRAL 5082 03:19:15,799 --> 03:19:20,336 RILY INFECTED CELL WILL BE 5083 03:19:20,336 --> 03:19:21,004 ACTIVE. 5084 03:19:21,004 --> 03:19:22,405 THERE'S A DIRECT ACTIVATION OF 5085 03:19:22,405 --> 03:19:24,641 THE MONOCYTE IN THOSE CASES. 5086 03:19:24,641 --> 03:19:26,609 BUT DELIVERY AND PACKAGING OF 5087 03:19:26,609 --> 03:19:29,846 THE TISSUE FACTOR FROM THE VIRAL 5088 03:19:29,846 --> 03:19:31,614 INFECT CELLS IS MORE DEBATABLE 5089 03:19:31,614 --> 03:19:33,249 EXACTLY HOW THAT'S CONTRIBUTING 5090 03:19:33,249 --> 03:19:37,220 TO DIC, BUT THERE IS DIRECT -- 5091 03:19:37,220 --> 03:19:40,957 WITH THE EMERGING HEMORRHAGIC 5092 03:19:40,957 --> 03:19:41,191 VIRUSES. 5093 03:19:41,191 --> 03:19:46,596 >> ONE QUICK FOLLOW-UP COMMENT 5094 03:19:46,596 --> 03:19:47,464 TO NIGEL'S QUESTION IN REGARDS 5095 03:19:47,464 --> 03:19:49,232 TO ALL THE TOXIC MOLECULES THAT 5096 03:19:49,232 --> 03:19:51,067 ARE RELEASED WHEN YOU DISMANTLE 5097 03:19:51,067 --> 03:19:53,903 THE SCAFFOLD THAT IS DNA. 5098 03:19:53,903 --> 03:19:56,206 THERE ARE HOST ACUTE PHASE 5099 03:19:56,206 --> 03:19:57,740 PROTEINS SUCH AS C REACTIVE PRO 5100 03:19:57,740 --> 03:20:01,644 TPROTEIN THAT CAN NEUTRALIZE 5101 03:20:01,644 --> 03:20:03,613 HISTONES, SO MAYBE THERE ARE 5102 03:20:03,613 --> 03:20:07,517 SAFETY MECHANISMS IN PLACE TO 5103 03:20:07,517 --> 03:20:13,790 NEUTRALIZE THOSE MEDIATORS. 5104 03:20:13,790 --> 03:20:16,493 >> IF I REMEMBER MINUTE FILL -- 5105 03:20:16,493 --> 03:20:18,962 THERE ARE STUDIES DONE LIKE THE 5106 03:20:18,962 --> 03:20:22,131 BACTEREMIA STUDIES AND OTHERS 5107 03:20:22,131 --> 03:20:25,435 HAVE SHOWN THAT IF THEY GIVE 5108 03:20:25,435 --> 03:20:26,936 DNASE, THE LIVER INJURY WAS NOT 5109 03:20:26,936 --> 03:20:29,572 PREVENTED. 5110 03:20:29,572 --> 03:20:31,140 THEY GIVE NEUTRALIZING STONES IT 5111 03:20:31,140 --> 03:20:33,476 WAS NOT PREVENTED AND FINALLY IT 5112 03:20:33,476 --> 03:20:36,513 WAS FOUND THAT IT WAS ALL THE 5113 03:20:36,513 --> 03:20:37,847 NEUTROPHIL ELASTASE THAT WAS 5114 03:20:37,847 --> 03:20:41,017 STILL THERE AND THEY TAGGED -- 5115 03:20:41,017 --> 03:20:45,488 SORRY, GO AHEAD. 5116 03:20:45,488 --> 03:20:49,292 >> THE NEUTROPHIL EE LAS TAINS 5117 03:20:49,292 --> 03:20:50,093 AND HISTONES. 5118 03:20:50,093 --> 03:20:51,928 >> FOR EVERYONE'S KNOWLEDGE, SO 5119 03:20:51,928 --> 03:20:55,598 WHY DO YOU THINK DFPI FAILED IN 5120 03:20:55,598 --> 03:20:55,932 SEPSIS? 5121 03:20:55,932 --> 03:20:57,267 DO YOU HAVE ANY -- I'VE HEARD A 5122 03:20:57,267 --> 03:20:59,235 LOT ABOUT THIS, YOU KNOW, WHEN 5123 03:20:59,235 --> 03:21:01,037 YOU GO TO SEPSIS TALKS, THEY 5124 03:21:01,037 --> 03:21:04,107 TALK ABOUT THIS TFPI CLINICAL 5125 03:21:04,107 --> 03:21:05,408 TRIALS BUT SOME PEOPLE STILL 5126 03:21:05,408 --> 03:21:07,176 BELIEVE THAT IT WAS NOT THE 5127 03:21:07,176 --> 03:21:07,710 PROPER TRIAL. 5128 03:21:07,710 --> 03:21:12,282 IS THERE ANY REASON YOU THINK 5129 03:21:12,282 --> 03:21:15,351 THAT WHY TFPI DIDN'T WORK? 5130 03:21:15,351 --> 03:21:18,187 >> I THINK IT'S POTENCY AND ALSO 5131 03:21:18,187 --> 03:21:18,421 TIMING. 5132 03:21:18,421 --> 03:21:20,189 YOU HAVE TO GET THAT DRIG IN AT 5133 03:21:20,189 --> 03:21:20,924 THE EARLY PHASE. 5134 03:21:20,924 --> 03:21:24,060 IF YOU GET IT IN TOO LATE, IT 5135 03:21:24,060 --> 03:21:28,331 NOT GOING TO DO ANYTHING. 5136 03:21:28,331 --> 03:21:30,300 6.1% -- IS NOT PARTICULARLY 5137 03:21:30,300 --> 03:21:32,569 IMPRESSIVE, SO DEPENDING ON HOW 5138 03:21:32,569 --> 03:21:35,538 YOU DESIGN THE TRIAL, AND THE -- 5139 03:21:35,538 --> 03:21:39,509 THEY ADDED HELP TRIN ON TOP, SO 5140 03:21:39,509 --> 03:21:45,648 THAT THEN COMPROMISED LACKING AT 5141 03:21:45,648 --> 03:21:46,983 THE -- HALF THE POPULATION GOT 5142 03:21:46,983 --> 03:21:47,417 HEPARIN AS WELL. 5143 03:21:47,417 --> 03:21:48,785 SO I THINK THE EARLY EXCITEMENT 5144 03:21:48,785 --> 03:21:51,854 OF USING THESE ANTICOAGULANTS 5145 03:21:51,854 --> 03:21:55,358 WAS SOMEWHAT -- THE TRIALS 5146 03:21:55,358 --> 03:21:58,294 WEREN'T AS DESIGNED, AND I THINK 5147 03:21:58,294 --> 03:22:00,229 WE CAN DO A MUCH BETTER JOB IF 5148 03:22:00,229 --> 03:22:02,699 WE STARTED TOMORROW DESIEB DESIA 5149 03:22:02,699 --> 03:22:03,199 NEW TRIAL. 5150 03:22:03,199 --> 03:22:05,602 AND CERTAINLY WHAT'S FASCINATING 5151 03:22:05,602 --> 03:22:07,003 TO ME IS IT ONLY EFFECTIVE IN 5152 03:22:07,003 --> 03:22:08,605 PATIENTS WITH A DIC. 5153 03:22:08,605 --> 03:22:10,139 IT'S COMPLETELY INEFFECTIVE IN 5154 03:22:10,139 --> 03:22:12,208 PATIENTS WITHOUT DIC. 5155 03:22:12,208 --> 03:22:14,410 SO THERE'S A GOOD SORT OF 5156 03:22:14,410 --> 03:22:16,346 INDICATION THAT YOU'VE GOT TO 5157 03:22:16,346 --> 03:22:18,348 HAVE DIC BEFORE -- IF YOU GAVE 5158 03:22:18,348 --> 03:22:21,584 TO THE WHOLE POPULATION, IT 5159 03:22:21,584 --> 03:22:22,785 FAILS. 5160 03:22:22,785 --> 03:22:26,055 AND IN A SEPTIC BASIC 5161 03:22:26,055 --> 03:22:26,623 POPULATION, IT FAILED. 5162 03:22:26,623 --> 03:22:29,125 >> OKAY. 5163 03:22:29,125 --> 03:22:34,464 SO DO THEY HAVE ANY CHARACTERS 5164 03:22:34,464 --> 03:22:37,734 WAY OF IDENTIFYING PATIENTS WHO 5165 03:22:37,734 --> 03:22:41,337 ARE DEVELOPING DIC VERSUS NOT 5166 03:22:41,337 --> 03:22:44,140 DIC OR ARE THEY JUST SAYING 5167 03:22:44,140 --> 03:22:44,941 THAT'S SEPSIS? 5168 03:22:44,941 --> 03:22:48,511 >> THEY DO ROUTINELY COLLECT THE 5169 03:22:48,511 --> 03:22:54,183 INR DEDIMER IN FIBRINOGEN SO IT 5170 03:22:54,183 --> 03:22:57,453 CAN BE -- ICU PATIENTS WITH 5171 03:22:57,453 --> 03:22:58,588 SEPSIS, ROUGHLY ONE-THIRD OF 5172 03:22:58,588 --> 03:23:04,527 THEM DID HAVE DI THIC, AND THE 5173 03:23:04,527 --> 03:23:06,195 CHALLENGE IS TO IDENTIFY 5174 03:23:06,195 --> 03:23:09,098 BIOMARKERS THAT PREDICT DIC. 5175 03:23:09,098 --> 03:23:15,038 SO WE FOUND THAT ANTITHROMBIN 5176 03:23:15,038 --> 03:23:17,874 COCONSUMPTION AND ALSO PROTEIN C 5177 03:23:17,874 --> 03:23:19,475 CONSUMPTION WERE USEFUL TO 5178 03:23:19,475 --> 03:23:22,011 PREDICT THE PRE-DIC STATE. 5179 03:23:22,011 --> 03:23:27,016 BUT I DON'T KNOW IF CLINICALLY 5180 03:23:27,016 --> 03:23:30,920 DIC STATUS CHANGES TREATMENT 5181 03:23:30,920 --> 03:23:31,220 STRATEGIES. 5182 03:23:31,220 --> 03:23:32,889 >> THANK YOU VERY MUCH. 5183 03:23:32,889 --> 03:23:34,323 AND I THINK I WILL HAVE ONE MORE 5184 03:23:34,323 --> 03:23:38,461 QUESTION TO BOTH NIGEL AND -- SO 5185 03:23:38,461 --> 03:23:39,862 WHAT ABOUT THE ROLE FOR 5186 03:23:39,862 --> 03:23:42,598 ENDOTHELIAL TISSUE FACTOR? 5187 03:23:42,598 --> 03:23:47,470 IS IT IMPORTANT OR HOW THAT 5188 03:23:47,470 --> 03:23:48,938 PLAYS IN CONTEXT? 5189 03:23:48,938 --> 03:23:50,773 >> WELL, I CAN TELL YOU IF YOU 5190 03:23:50,773 --> 03:23:52,642 PUT AN ANTIBODY AGAINST TISSUE 5191 03:23:52,642 --> 03:23:55,111 FACTOR IN ILS MODEL, YOU BLOCK 5192 03:23:55,111 --> 03:23:57,113 ABOUT 80 TO 85% OF THE 5193 03:23:57,113 --> 03:23:58,481 ACTIVATION OF COAGULATION. 5194 03:23:58,481 --> 03:24:01,751 IF YOU SELECTIVELY TARGET THE 5195 03:24:01,751 --> 03:24:02,719 HEMATOPOIETIC CELL POPULATION, 5196 03:24:02,719 --> 03:24:04,187 YOU BLOCK ABOUT 50%. 5197 03:24:04,187 --> 03:24:09,425 SO WE CAN CONCLUDE THAT THE 5198 03:24:09,425 --> 03:24:10,593 MONOCYTES -- COMING FROM ANOTHER 5199 03:24:10,593 --> 03:24:13,129 SOURCE, WHICH WE BELIEVE IS 5200 03:24:13,129 --> 03:24:14,831 INCREASED VASCULAR PERMEABILITY, 5201 03:24:14,831 --> 03:24:17,133 NOT THE ENDOTHELIAL CELLS, SO 5202 03:24:17,133 --> 03:24:21,504 WHEN WE DID THE TI TISSUE FACTON 5203 03:24:21,504 --> 03:24:24,640 MICE, WE ACTUALLY DIDN'T SEW 5204 03:24:24,640 --> 03:24:26,175 ANOTHER -- PEOPLE ARE A LITTLE 5205 03:24:26,175 --> 03:24:27,376 UPSET US BECAUSE THEY SPENT 5206 03:24:27,376 --> 03:24:32,515 YEARS WORKING ON -- WELL, THE 5207 03:24:32,515 --> 03:24:33,616 DATA IS DATA. 5208 03:24:33,616 --> 03:24:36,886 IT'S NOT DOING ANYTHING THAT WE 5209 03:24:36,886 --> 03:24:40,056 CAN DETECT. 5210 03:24:40,056 --> 03:24:42,125 IF YOU INCREASE VASCULAR 5211 03:24:42,125 --> 03:24:42,992 PERMEABILITY, WHAT ARE YOU GOING 5212 03:24:42,992 --> 03:24:43,326 TO DO? 5213 03:24:43,326 --> 03:24:44,594 YOU'RE GOING TO EXPOSE THAT 5214 03:24:44,594 --> 03:24:45,394 TISSUE FACTOR AND THAT'S GOING 5215 03:24:45,394 --> 03:24:46,462 TO LEAD TO AN ACTIVATION. 5216 03:24:46,462 --> 03:24:47,964 SO I THINK IF YOU WANT TO 5217 03:24:47,964 --> 03:24:49,098 COMPLETELY BLOCK THE TISSUE 5218 03:24:49,098 --> 03:24:50,600 FACTOR ACTIVATION OF 5219 03:24:50,600 --> 03:24:51,701 COAGULATION, YOU'D HAVE TO BLOCK 5220 03:24:51,701 --> 03:24:55,738 THE MONOCYTE AND PROTECT THE 5221 03:24:55,738 --> 03:24:58,141 VASCULAR -- SUCH AS APC, THIS 5222 03:24:58,141 --> 03:25:03,646 SITE OF PROTECTIVE APC -- 5223 03:25:03,646 --> 03:25:07,950 >> AND I THINK THERE IS ONE 5224 03:25:07,950 --> 03:25:11,788 QUESTION FOR -- CHAT BOX, YOU 5225 03:25:11,788 --> 03:25:12,922 CAN READ THAT, BUT I HAVE ONE 5226 03:25:12,922 --> 03:25:15,024 MORE QUESTION. 5227 03:25:15,024 --> 03:25:16,459 FOR MY GEL. 5228 03:25:16,459 --> 03:25:18,861 SO EXTRACELLULAR VESICLES, WOULD 5229 03:25:18,861 --> 03:25:20,163 THAT EXPRESS TISSUE FACTOR, THEY 5230 03:25:20,163 --> 03:25:23,032 HAVE TO BE EXCLUSIVELY DERIVED 5231 03:25:23,032 --> 03:25:24,534 FROM MONOCYTES, BECAUSE 5232 03:25:24,534 --> 03:25:25,635 PLATELETS -- CORRECT ME, 5233 03:25:25,635 --> 03:25:27,370 PLATELETS DON'T EXPRESS TISSUE 5234 03:25:27,370 --> 03:25:27,804 FACTOR, RIGHT? 5235 03:25:27,804 --> 03:25:30,740 >> IN OUR VIEW. 5236 03:25:30,740 --> 03:25:32,041 IT A LITTLE CONTROVERSIAL, BUT 5237 03:25:32,041 --> 03:25:34,744 IN OUR VIEW, THEY DON'T EXPRESS 5238 03:25:34,744 --> 03:25:36,779 TISSUE FACTOR. 5239 03:25:36,779 --> 03:25:40,983 BUT A STUDY SHOWED IF HE DAMAGED 5240 03:25:40,983 --> 03:25:43,019 THE VASCULATURE, HE GOT EXTRA 5241 03:25:43,019 --> 03:25:46,088 VASCULAR TISSUE POSITIVE TISSUES 5242 03:25:46,088 --> 03:25:46,522 COMING OUT. 5243 03:25:46,522 --> 03:25:48,291 SO ALL CELLS CAN RELEASE TISSUE 5244 03:25:48,291 --> 03:25:49,659 FACTOR IF THEY CAN EXPRESS IT ON 5245 03:25:49,659 --> 03:25:50,226 THE SURFACE. 5246 03:25:50,226 --> 03:25:54,797 SO WHEN WE LOOK AT THAT EV 5247 03:25:54,797 --> 03:25:55,865 TISSUE FACTOR, WE CAN'T TELL YOU 5248 03:25:55,865 --> 03:25:57,834 WHERE IT'S FROM, WE JUST KNOW IT 5249 03:25:57,834 --> 03:25:58,601 ELEVATED IN THE CIRCULATION. 5250 03:25:58,601 --> 03:26:01,537 A LOT OF IT IS PROBABLY COMING 5251 03:26:01,537 --> 03:26:04,073 FROM THE MONOCYTES BUT WE CAN'T 5252 03:26:04,073 --> 03:26:10,746 EXCLUSIVELY SAY -- ON THE 5253 03:26:10,746 --> 03:26:12,014 MONOCYTE AND MACROPHAGES. 5254 03:26:12,014 --> 03:26:14,317 I THINK IN THE ENDOTHELIAL 5255 03:26:14,317 --> 03:26:17,820 CELLS, WHY THEY NEED THE 5256 03:26:17,820 --> 03:26:20,623 INDUCTION, IN REAL SEPSIS, THE 5257 03:26:20,623 --> 03:26:24,560 TISSUE FACTOR FROM END THEEL 5258 03:26:24,560 --> 03:26:26,062 YELL CELLS CAN ALSO CONTRIBUTE 5259 03:26:26,062 --> 03:26:28,264 TO THE COAGULATION. 5260 03:26:28,264 --> 03:26:31,534 >> GREAT STUDY MANY YEARS AGO 5261 03:26:31,534 --> 03:26:33,836 AND HE -- AND REALLY COULDN'T 5262 03:26:33,836 --> 03:26:35,271 FIND IT APART FROM A COUPLE 5263 03:26:35,271 --> 03:26:36,672 SOURCES, AND THEN THE 5264 03:26:36,672 --> 03:26:38,207 DIFFICULTIES, IF YOU SEE A 5265 03:26:38,207 --> 03:26:39,308 POSITIVE ENDOTHELIAL CELL, THEY 5266 03:26:39,308 --> 03:26:40,610 DON'T KNOW WHETHER THE 5267 03:26:40,610 --> 03:26:41,711 ENDOTHELIAL CELL MADE IT OR 5268 03:26:41,711 --> 03:26:43,880 WHETHER THE VESICLE FROM A 5269 03:26:43,880 --> 03:26:44,947 MONOCYTE GOT BOUND TO THAT AND 5270 03:26:44,947 --> 03:26:48,017 THAT CAUSED THE SIGNAL BEING 5271 03:26:48,017 --> 03:26:51,087 ELEVATED IN THE ENTHEEL YELL 5272 03:26:51,087 --> 03:26:51,387 CELL. 5273 03:26:51,387 --> 03:26:51,921 >> GO AHEAD. 5274 03:26:51,921 --> 03:26:57,193 THERE IS A QUESTION FOR YOU -- 5275 03:26:57,193 --> 03:26:59,695 >> -- OF ANTI-COAGULATION IN 5276 03:26:59,695 --> 03:27:01,030 SEPSIS, I THINK TIME SOMETHING A 5277 03:27:01,030 --> 03:27:03,633 CRITICAL ISSUE. 5278 03:27:03,633 --> 03:27:08,004 OUR DIAGNOSIS OF DIC IS BASED ON 5279 03:27:08,004 --> 03:27:11,173 THE SCORE -- I THINK MOST FASTER 5280 03:27:11,173 --> 03:27:12,909 TIMING FOR INTERVENTION FOR 5281 03:27:12,909 --> 03:27:13,976 COAGULATION I THINK IS AT THE 5282 03:27:13,976 --> 03:27:17,847 EARLY STAGE. 5283 03:27:17,847 --> 03:27:19,282 AFTER THAT TIME, THOSE PATIENTS 5284 03:27:19,282 --> 03:27:25,087 MAY NOT REACH THE DIC CRITERIA. 5285 03:27:25,087 --> 03:27:26,923 >> FROM ALL OF YOUR TALKS, ONE 5286 03:27:26,923 --> 03:27:28,324 THING I UNDERSTOOD, YOU CAN ALL 5287 03:27:28,324 --> 03:27:29,959 CORRECT ME, THAT THE LATE 5288 03:27:29,959 --> 03:27:32,695 STAGES, THE MORE INFLAMMATORY 5289 03:27:32,695 --> 03:27:35,398 STAGE THE POPULATION IS DRIVEN 5290 03:27:35,398 --> 03:27:37,600 BY PRIMARILY INFLAMMATION. 5291 03:27:37,600 --> 03:27:39,235 >> NO, I DON'T AGREE WITH THAT 5292 03:27:39,235 --> 03:27:39,502 STATEMENT. 5293 03:27:39,502 --> 03:27:40,970 I THINK THE EARLY PHASE IS 5294 03:27:40,970 --> 03:27:43,039 INFLAMMATION AND COAGULATION. 5295 03:27:43,039 --> 03:27:47,543 AND THE LATER STAGE IS MORE OF A 5296 03:27:47,543 --> 03:27:48,844 COMPLEMENT -- SO THAT IS CLEARLY 5297 03:27:48,844 --> 03:27:50,313 COMING OUT OF THE -- STUDIES, 5298 03:27:50,313 --> 03:27:52,214 THERE WERE TWO PHASES. 5299 03:27:52,214 --> 03:27:53,416 BUT INFLAMMATION GOES UP VERY, 5300 03:27:53,416 --> 03:27:55,518 VERY RAPIDLY, IN THE MOUSE 5301 03:27:55,518 --> 03:27:57,453 MODEL, TNF IS UP BY ONE HOUR. 5302 03:27:57,453 --> 03:27:59,622 THE OTHER INFLAMMATORY MEDIA IS 5303 03:27:59,622 --> 03:28:00,523 THREE TO FOUR HOURS AND THEN 5304 03:28:00,523 --> 03:28:01,057 THEY'RE ELEVATED. 5305 03:28:01,057 --> 03:28:02,825 SO THE FIRST TP PHASE IS COY AGO 5306 03:28:02,825 --> 03:28:05,561 LAITION AND INFLAMMATION, AND I 5307 03:28:05,561 --> 03:28:08,798 DON'T THINK THEY'RE AS CLOSELY 5308 03:28:08,798 --> 03:28:15,271 CONNECTED AN AS EVERYBODY WOULD 5309 03:28:15,271 --> 03:28:17,206 LIKE THEM CONNECTED. 5310 03:28:17,206 --> 03:28:18,741 CROSSTALK GOES UP INDEPENDENTLY 5311 03:28:18,741 --> 03:28:19,508 AS WELL. 5312 03:28:19,508 --> 03:28:22,912 >> YEAH, BECAUSE LIKE I REMEMBER 5313 03:28:22,912 --> 03:28:27,717 DURING COVID, THERE WOULD BE 5314 03:28:27,717 --> 03:28:28,684 FIVE, SIX RECEPTOR TRIALS AND 5315 03:28:28,684 --> 03:28:29,785 THEY ALSO FOUND THE SAME THING, 5316 03:28:29,785 --> 03:28:31,954 THEY WERE MORE EFFECTIVE AT THE 5317 03:28:31,954 --> 03:28:33,255 LATER STAGE, AM I RIGHT? 5318 03:28:33,255 --> 03:28:33,489 CORRECT? 5319 03:28:33,489 --> 03:28:35,224 >> YES. 5320 03:28:35,224 --> 03:28:37,860 AND I WONDER IF THAT'S 5321 03:28:37,860 --> 03:28:39,061 BECAUSE -- I REALLY DON'T KNOW 5322 03:28:39,061 --> 03:28:41,364 THE MECHANISM. 5323 03:28:41,364 --> 03:28:42,365 INTUITIVELY, IT DOESN'T REALLY 5324 03:28:42,365 --> 03:28:43,466 MAKE SENSE. 5325 03:28:43,466 --> 03:28:48,571 BUT MAYBE HAVING IL-6 5326 03:28:48,571 --> 03:28:49,672 NEUTRALIZED TOO EARLY IS 5327 03:28:49,672 --> 03:28:53,042 HARMFUL, BECAUSE YOU DO NEED AN 5328 03:28:53,042 --> 03:28:54,343 INFLAMMATORY RESPONSE TO FIGHT 5329 03:28:54,343 --> 03:28:55,344 THE INFECTION IN THE FIRST 5330 03:28:55,344 --> 03:28:57,646 PLACE. 5331 03:28:57,646 --> 03:29:01,784 >> I HAVE A LAST QUESTION FOR 5332 03:29:01,784 --> 03:29:09,158 THIS FOR ZHENYU. 5333 03:29:09,158 --> 03:29:12,428 SO -- WHERE THAT FIT IN THE 5334 03:29:12,428 --> 03:29:17,133 INFLAM ZONE DRIVEN COAGULOPATHY? 5335 03:29:17,133 --> 03:29:18,000 >> WHAT'S THE QUESTION? 5336 03:29:18,000 --> 03:29:21,570 >> SO I'M SAYING THAT JUST 5337 03:29:21,570 --> 03:29:23,873 WONDERING, WHEN THE INFLAMMASOME 5338 03:29:23,873 --> 03:29:27,576 ACTIVATION IS CLASSICALLY 5339 03:29:27,576 --> 03:29:28,911 ASSOCIATED WITH -- WHICH CAN 5340 03:29:28,911 --> 03:29:31,280 BIND TO RECEPTOR AND PROMOTE 5341 03:29:31,280 --> 03:29:32,281 THROMBOINFLAMMATION. 5342 03:29:32,281 --> 03:29:34,784 SO IN THE PIE ROP PTOSIS DRIVEN 5343 03:29:34,784 --> 03:29:37,753 COAGULATION PATHWAY, HOW WOULD 5344 03:29:37,753 --> 03:29:47,897 THIS IL -- I DIDN'T SEE THAT 5345 03:29:47,897 --> 03:29:48,731 INTERLEUKIN ONE BETA. 5346 03:29:48,731 --> 03:29:54,570 >> YEAH, WE TESTED THIS 5347 03:29:54,570 --> 03:29:56,172 INFORMATION -- THE CYTOKINES IN 5348 03:29:56,172 --> 03:30:04,080 THE COAGULATION FOR -- AND FOUND 5349 03:30:04,080 --> 03:30:05,414 INTERLEUKIN ONE BETA AND 5350 03:30:05,414 --> 03:30:06,682 INTERLEUKIN 18 ACTUALLY DO NOT 5351 03:30:06,682 --> 03:30:08,017 CONTRIBUTE TO COAGULATION. 5352 03:30:08,017 --> 03:30:10,419 SO MAINLY OUR CONCLUSION IS THAT 5353 03:30:10,419 --> 03:30:14,990 TISSUE FACTOR RELEASED FROM 5354 03:30:14,990 --> 03:30:16,659 THE -- CELLS. 5355 03:30:16,659 --> 03:30:19,829 >> SO BEN CONFIRMS THAT BECAUSE 5356 03:30:19,829 --> 03:30:23,199 HE TOOK THE IL-1 RECEPTOR IN 5357 03:30:23,199 --> 03:30:25,901 KNOCKOUT MICE AND LOOKED AT THE 5358 03:30:25,901 --> 03:30:27,403 EFFECT ON THE COAGULOPATHY AND 5359 03:30:27,403 --> 03:30:34,343 THERE WAS NO EFFECT AS ALL. 5360 03:30:34,343 --> 03:30:37,146 >> THERE IS A QUESTION FOR WOT H 5361 03:30:37,146 --> 03:30:37,379 OF YOU. 5362 03:30:37,379 --> 03:30:41,283 I DON'T KNOW IF WE HAVE TIME OR 5363 03:30:41,283 --> 03:30:44,019 NOT, BUT -- TO RELEASE TISSUE 5364 03:30:44,019 --> 03:30:45,588 FACTOR IS THE QUESTION. 5365 03:30:45,588 --> 03:30:47,656 >> IN OUR VIEW, NO. 5366 03:30:47,656 --> 03:30:49,091 THE ONLY THING WE FOUND TO 5367 03:30:49,091 --> 03:30:52,261 INDUCE TISSUE FACTOR MON SUIT MS 5368 03:30:52,261 --> 03:30:54,096 ARE LPC. 5369 03:30:54,096 --> 03:30:56,732 THERE ARE SOME SPORADIC VERY 5370 03:30:56,732 --> 03:31:00,402 HIGH DOSE STUDIES WITH 5371 03:31:00,402 --> 03:31:01,637 MONOCYTES, WHICH YOU ALWAYS ARE 5372 03:31:01,637 --> 03:31:03,372 CONCERNED ABOUT LPS 5373 03:31:03,372 --> 03:31:06,008 CONTAMINATION OF THE CYTOKINE, 5374 03:31:06,008 --> 03:31:08,844 BUT I HAVEN'T SEEN NATISH EU 5375 03:31:08,844 --> 03:31:09,778 FACTOR IN MONOCYTES. 5376 03:31:09,778 --> 03:31:12,014 >> I THINK I'M USING THE BREAKS, 5377 03:31:12,014 --> 03:31:14,416 SO SHALL WE GO ON THE BREAK? 5378 03:31:14,416 --> 03:31:17,453 >> YES, LET TAKE A BREAK AND I 5379 03:31:17,453 --> 03:31:18,787 THINK ACCORDING TO THE AGENDA, 5380 03:31:18,787 --> 03:31:21,690 WE WILL BE BACK AT 2:15, I 5381 03:31:21,690 --> 03:31:24,560 GUESS? 5382 03:31:24,560 --> 03:31:26,829 >> THANKS TO EVERYONE. 5383 03:31:26,829 --> 03:31:28,063 REALLY WONDERFUL TALKS. 5384 03:31:28,063 --> 03:31:29,031 I'M SURE EVERYBODY LEARNED A 5385 03:31:29,031 --> 03:31:35,618 LOT. THANK YOU. 5386 03:31:35,618 --> 03:31:37,152 SO WHO ISN'T FAMILIAR WITH 5387 03:31:37,152 --> 03:31:39,321 ARTIFICIAL INTELLIGENCE THESE 5388 03:31:39,321 --> 03:31:40,389 DAYS, THANKS TO THE MEDIA, AND 5389 03:31:40,389 --> 03:31:43,792 WE ARE EXCITED TO SEE HOW A.I. 5390 03:31:43,792 --> 03:31:45,894 CAN BE USED FOR SEPSIS RESEARCH. 5391 03:31:45,894 --> 03:31:48,931 SO I WOULD LIKE TO INVITE 5392 03:31:48,931 --> 03:31:52,201 DR. VINCENT LIU FROM KAISER 5393 03:31:52,201 --> 03:31:53,869 PERMANENTE AND DR. IOANNIS 5394 03:31:53,869 --> 03:31:55,504 KOUTROULIS FROM GEORGE 5395 03:31:55,504 --> 03:31:57,306 WASHINGTON UNIVERSITY AND 5396 03:31:57,306 --> 03:31:57,973 CHILDREN'S NATIONAL HOSPITAL TO 5397 03:31:57,973 --> 03:31:59,975 LEAD THIS UPCOMING SESSION. 5398 03:31:59,975 --> 03:32:02,278 PLEASE GO AHEAD. 5399 03:32:02,278 --> 03:32:03,712 >> THANK YOU SO MUCH. 5400 03:32:03,712 --> 03:32:05,881 I AGREE WITH YOU, IF YOU HAVEN'T 5401 03:32:05,881 --> 03:32:07,516 HEARD OF A.I., YOUR HEAD IS 5402 03:32:07,516 --> 03:32:09,418 TRULY BURIED IN THE SAND, OR YOU 5403 03:32:09,418 --> 03:32:12,187 LIVE IN ONE OF THESE POPULATIONS 5404 03:32:12,187 --> 03:32:15,157 THAT'S NEVER BEEN TOUCHED 5405 03:32:15,157 --> 03:32:15,591 BEFORE. 5406 03:32:15,591 --> 03:32:17,993 IT MY PLEASURE REALLY TO BE 5407 03:32:17,993 --> 03:32:19,995 JOINED BY DR. IOANNIS KOUTROULIS 5408 03:32:19,995 --> 03:32:24,900 AS WE HOPE TO, YOU KNOW, OVERSEE 5409 03:32:24,900 --> 03:32:26,302 SOME OF THE MOST INNOVATIVE AND 5410 03:32:26,302 --> 03:32:27,736 IMPORTANT WORK THAT'S HAPPENING 5411 03:32:27,736 --> 03:32:28,704 IN A.I. AND SEPSIS. 5412 03:32:28,704 --> 03:32:31,106 I THINK IT'S GOING TO BE A 5413 03:32:31,106 --> 03:32:31,874 FANTASTIC TOUR THROUGH THE 5414 03:32:31,874 --> 03:32:32,808 DIFFERENT OPPORTUNITIES, AS WELL 5415 03:32:32,808 --> 03:32:34,076 AS CHALLENGES. 5416 03:32:34,076 --> 03:32:37,446 SO WITH THAT, I'M GOING TO TURN 5417 03:32:37,446 --> 03:32:39,315 IT OVER TO OUR FIRST PRESENTER, 5418 03:32:39,315 --> 03:32:40,749 DR. ANDRE HOLDER, WHO'S JOINING 5419 03:32:40,749 --> 03:32:43,152 US FROM EMORY UNIVERSITY TO 5420 03:32:43,152 --> 03:32:44,787 SPEAK ON TOWARDS EARLIER 5421 03:32:44,787 --> 03:32:46,455 RECOGNITION: A.I. IN SEPSIS 5422 03:32:46,455 --> 03:32:49,525 PREDICTION AND PROGNOSTICATION. 5423 03:32:49,525 --> 03:32:52,995 DR. HOLDER? 5424 03:32:52,995 --> 03:32:53,962 >> YES. 5425 03:32:53,962 --> 03:32:54,730 GOOD AFTERNOON. 5426 03:32:54,730 --> 03:32:58,567 CAN EVERYONE HEAR ME OKAY? 5427 03:32:58,567 --> 03:32:59,034 >> YES. 5428 03:32:59,034 --> 03:33:00,536 >> PERFECT. 5429 03:33:00,536 --> 03:33:02,538 SO THANK YOU FOR THE 5430 03:33:02,538 --> 03:33:02,938 INTRODUCTION. 5431 03:33:02,938 --> 03:33:05,974 SO AGAIN, MY TALK IS GOING TO BE 5432 03:33:05,974 --> 03:33:07,543 ON A.I. SEPSIS PREDICTION AND 5433 03:33:07,543 --> 03:33:11,647 PROGRPROGNOSTICATION. 5434 03:33:11,647 --> 03:33:14,383 SO THE OBJECTIVES HERE ARE TO 5435 03:33:14,383 --> 03:33:16,251 DISCUSS EXISTING AND EMERGING 5436 03:33:16,251 --> 03:33:17,319 APPROACHES TO SEPSIS PREDICTION 5437 03:33:17,319 --> 03:33:18,754 MODELING USING A.I. AND THEIR 5438 03:33:18,754 --> 03:33:19,955 EFFECTS ON PATIENT OUTCOMES, AND 5439 03:33:19,955 --> 03:33:22,458 I'M GOING TO USE A COUPLE OF 5440 03:33:22,458 --> 03:33:23,892 EXAMPLES FROM WORK FROM MYSELF 5441 03:33:23,892 --> 03:33:25,928 AND MY COLLABORATORS, BUT 5442 03:33:25,928 --> 03:33:27,162 THERE'S TONS OF OTHER WORK OUT 5443 03:33:27,162 --> 03:33:28,364 THERE THAT TOUCHES ON THE SAME 5444 03:33:28,364 --> 03:33:29,665 THING. 5445 03:33:29,665 --> 03:33:30,899 THE SECOND OBJECTIVE IS TO 5446 03:33:30,899 --> 03:33:32,167 HIGHLIGHT EXAMPLES OF BOTH 5447 03:33:32,167 --> 03:33:33,202 SUCCESSES AND CHALLENGES ACROSS 5448 03:33:33,202 --> 03:33:36,238 THE FIELD THAT ENLIGHTEN -- THAT 5449 03:33:36,238 --> 03:33:37,373 CAN ENLIGHTEN THE AUDIENCE ABOUT 5450 03:33:37,373 --> 03:33:38,407 WHERE THE FIELD NEEDS TO BE 5451 03:33:38,407 --> 03:33:40,042 MOVING. 5452 03:33:40,042 --> 03:33:45,748 SO MY FINANCIAL DISCLOSURES. 5453 03:33:45,748 --> 03:33:48,150 SO FIRST, LET'S TALK ABOUT WHAT 5454 03:33:48,150 --> 03:33:50,886 A.I. IS. 5455 03:33:50,886 --> 03:33:52,388 SO ARTIFICIAL INTELLIGENCE IS 5456 03:33:52,388 --> 03:33:53,922 SIMPLY THE USE OF MACHINES TO 5457 03:33:53,922 --> 03:33:56,158 SIMULATE THE ABILITY OF HUMANS 5458 03:33:56,158 --> 03:33:59,495 TO ACQUIRE KNOWLEDGE AND SKILLS. 5459 03:33:59,495 --> 03:34:01,063 AND HOW THOSE MACHINES DO THAT 5460 03:34:01,063 --> 03:34:02,398 IS THROUGH A PROCESS CALLED 5461 03:34:02,398 --> 03:34:02,898 MACHINE LEARNING. 5462 03:34:02,898 --> 03:34:04,400 AND IN THIS CASE, THE KNOWLEDGE 5463 03:34:04,400 --> 03:34:05,634 THAT WE'RE TRYING TO ACQUIRE IS 5464 03:34:05,634 --> 03:34:08,070 HOW TO PREDICT VARIOUS ASPECTS 5465 03:34:08,070 --> 03:34:10,572 OF SEPSIS, WHETHER IT'S SEPSIS 5466 03:34:10,572 --> 03:34:16,678 ITSELF OR ITS SEQUELAE. 5467 03:34:16,678 --> 03:34:18,313 NOW ONE THING THAT WE CAN DO IS 5468 03:34:18,313 --> 03:34:21,717 USE LABORATORY DATA, EMR DATA, 5469 03:34:21,717 --> 03:34:24,386 VITAL SIGNS, IMAGING, PERHAPS 5470 03:34:24,386 --> 03:34:25,554 OMICS AND GENETICS DATA, PUT 5471 03:34:25,554 --> 03:34:27,055 THAT INTO A MACHINE AND THEN 5472 03:34:27,055 --> 03:34:28,924 THAT MACHINE GENERATES SOME 5473 03:34:28,924 --> 03:34:32,528 OUTPUT WE FIND INFORMATIVE AND 5474 03:34:32,528 --> 03:34:35,164 HELPFUL WITH PATIENT CARE. 5475 03:34:35,164 --> 03:34:36,799 I TEND NOT TO LIKE TO USE THE 5476 03:34:36,799 --> 03:34:39,067 TERM ARTIFICIAL INTELLIGENCE 5477 03:34:39,067 --> 03:34:39,968 BECAUSE PEOPLE THINK OF 5478 03:34:39,968 --> 03:34:40,936 SOMETHING THAT'S AUTOMATED TO 5479 03:34:40,936 --> 03:34:42,137 TAKE THE PLACE OF HUMANS AND 5480 03:34:42,137 --> 03:34:43,439 REALLY THE WORK I WANT TO FOCUS 5481 03:34:43,439 --> 03:34:45,207 ON TODAY IS REALLY BEST 5482 03:34:45,207 --> 03:34:46,642 DESCRIBED AS AUGMENTED 5483 03:34:46,642 --> 03:34:47,075 INTELLIGENCE. 5484 03:34:47,075 --> 03:34:49,344 SO HOW CAN WE HELP PHYSICIANS 5485 03:34:49,344 --> 03:34:51,213 AND HEALTHCARE PROVIDERS ENHANCE 5486 03:34:51,213 --> 03:34:54,383 THEIR ABILITIES TO MAKE BETTER 5487 03:34:54,383 --> 03:34:55,918 PROGNOSTICATION AND PREDICTIONS 5488 03:34:55,918 --> 03:34:57,886 AS IT RELATES TO SEPSIS TO HELP 5489 03:34:57,886 --> 03:35:04,126 IMPROVE PATIENT CARE. 5490 03:35:04,126 --> 03:35:05,327 SO THE APPROACHES TO PREDICTION 5491 03:35:05,327 --> 03:35:06,762 AS IT PERTAINS TO SEPSIS AND THE 5492 03:35:06,762 --> 03:35:09,898 USE OF A.I. REALLY FOR ME FALL 5493 03:35:09,898 --> 03:35:10,466 INTO TWO CATEGORIES. 5494 03:35:10,466 --> 03:35:12,000 ONE WOULD BE TO PREDICT SEPSIS, 5495 03:35:12,000 --> 03:35:13,535 SO THAT IS IN PATIENTS WHO MAY 5496 03:35:13,535 --> 03:35:16,271 NOT HAVE CLINICAL SIGNS OF 5497 03:35:16,271 --> 03:35:18,974 SEVERE INFECTION, IDENTIFYING 5498 03:35:18,974 --> 03:35:19,875 WHO WILL BE AT RISK FOR 5499 03:35:19,875 --> 03:35:22,478 DEVELOPING IT, AND THEN ALSO 5500 03:35:22,478 --> 03:35:24,947 AMONG THOSE WHO ALREADY HAVE 5501 03:35:24,947 --> 03:35:26,148 SEPSIS, WHAT UNTOWARD OUTCOMES 5502 03:35:26,148 --> 03:35:27,316 CAN HAPPEN IN THE FUTURE, SUCH 5503 03:35:27,316 --> 03:35:29,918 AS DEATH OR, WORSE, AN ORGAN 5504 03:35:29,918 --> 03:35:31,787 FAILURE OR PERHAPS ONSET OF 5505 03:35:31,787 --> 03:35:35,290 SEPTIC SHOCK OR ACUTE FAILURE 5506 03:35:35,290 --> 03:35:36,058 REQUIRING MECHANICAL 5507 03:35:36,058 --> 03:35:38,794 VENTILATION. 5508 03:35:38,794 --> 03:35:40,429 SO AGAIN I'M GOING TO HIGHLIGHT 5509 03:35:40,429 --> 03:35:42,831 SOME WORK THAT WAS DONE BY MY 5510 03:35:42,831 --> 03:35:44,600 COLLABORATORS AND MYSELF, BUT 5511 03:35:44,600 --> 03:35:46,235 AGAIN, THERE ARE TONS OF OTHER 5512 03:35:46,235 --> 03:35:47,436 EXAMPLES IN THE LITERATURE. 5513 03:35:47,436 --> 03:35:48,937 SO TO HIGHLIGHT THE IDEA OF THE 5514 03:35:48,937 --> 03:35:52,774 USE OF A.I. FOR SEPSIS 5515 03:35:52,774 --> 03:35:54,910 PREDICTION, I'M GOING TO TOUCH 5516 03:35:54,910 --> 03:35:56,178 ON THIS WORK WE DID A FEW YEARS 5517 03:35:56,178 --> 03:35:56,411 BACK. 5518 03:35:56,411 --> 03:35:59,581 SO THE GOAL HERE WAS TO IDENTIFY 5519 03:35:59,581 --> 03:36:01,116 THOSE WHO WERE AT HIGHER RISK 5520 03:36:01,116 --> 03:36:02,751 FOR NEW ICU SEPSIS BEFORE IT 5521 03:36:02,751 --> 03:36:04,286 BECOMES CLINICALLY APPARENT. 5522 03:36:04,286 --> 03:36:14,129 WE USED A WEIBULL COX 5523 03:36:14,129 --> 03:36:16,965 PROPORTIONAL HAZARDS MODEL, WE 5524 03:36:16,965 --> 03:36:18,600 USED A LITTLE UNDER 80,000 5525 03:36:18,600 --> 03:36:19,568 PATIENTS TO TRAIN AND TEST THE 5526 03:36:19,568 --> 03:36:21,036 MODEL AT TWO DIFFERENT SITES, 5527 03:36:21,036 --> 03:36:23,305 AND USED VARIOUS CLINICAL 5528 03:36:23,305 --> 03:36:25,173 VARIABLES FROM THE EMR INCLUDING 5529 03:36:25,173 --> 03:36:27,242 VITAL SIGNS, DEMOGRAPHIC DATA, 5530 03:36:27,242 --> 03:36:31,613 LABORATORY DATA, ET CETERA. 5531 03:36:31,613 --> 03:36:34,783 AS YOU CAN SEE HERE, THE MODEL 5532 03:36:34,783 --> 03:36:37,085 THAT WE CREATED DETECTS SEPSIS 5533 03:36:37,085 --> 03:36:41,123 EARLIER, WITH AN AUC THAT'S 5534 03:36:41,123 --> 03:36:41,924 ABOUT .79 OR ABOVE. 5535 03:36:41,924 --> 03:36:43,125 NOW, WE HAVE A RANGE BECAUSE 5536 03:36:43,125 --> 03:36:46,161 WHAT WE DID WAS LOOK AT -- WE 5537 03:36:46,161 --> 03:36:47,296 USED DISCRETE TIME INTERVAL 5538 03:36:47,296 --> 03:36:48,330 ANALYSIS TO MAKE OUR 5539 03:36:48,330 --> 03:36:48,630 PREDICTIONS. 5540 03:36:48,630 --> 03:36:50,432 THAT IS, WHAT IS THE LIKELIHOOD 5541 03:36:50,432 --> 03:36:52,100 THE PATIENT MAY DEVELOP SEPSIS 5542 03:36:52,100 --> 03:36:53,001 FOUR HOURS FROM NOW, SIX HOURS 5543 03:36:53,001 --> 03:36:54,369 FROM NOW, EIGHT HOURS AND 12 5544 03:36:54,369 --> 03:36:54,836 HOURS. 5545 03:36:54,836 --> 03:36:57,205 THIS IS AKIN TO WHAT YOU MIGHT 5546 03:36:57,205 --> 03:36:58,173 SEE ON THE WEATHER CHANNEL 5547 03:36:58,173 --> 03:36:59,174 WHENEVER WE'RE TRYING TO MAKE 5548 03:36:59,174 --> 03:37:00,609 WEATHER PREDICTIONS. 5549 03:37:00,609 --> 03:37:02,010 SO -- AND THE KEY POINT I WANT 5550 03:37:02,010 --> 03:37:04,046 TO MAKE HERE, IF YOU LOOK -- IF 5551 03:37:04,046 --> 03:37:06,415 YOU FOCUS ON THAT GREEN SOLID 5552 03:37:06,415 --> 03:37:10,118 LINE ON THE BOTTOM, AS WE 5553 03:37:10,118 --> 03:37:11,453 INCREASE THAT TIME OVER WHICH 5554 03:37:11,453 --> 03:37:14,156 WE'RE TRYING TO PREDICT SEPSIS, 5555 03:37:14,156 --> 03:37:15,390 THE PERFORMANCE OF THE MODEL 5556 03:37:15,390 --> 03:37:16,792 DECREASE AND AGAIN, THIS IS AKIN 5557 03:37:16,792 --> 03:37:18,660 TO HOW WEATHER IS PREDICTED. 5558 03:37:18,660 --> 03:37:20,629 IT'S EASIER AND MORE ACCURATE TO 5559 03:37:20,629 --> 03:37:22,531 PREDICT WEATHER FROM -- SAY FROM 5560 03:37:22,531 --> 03:37:23,899 TODAY TO TOMORROW, VERSUS TRYING 5561 03:37:23,899 --> 03:37:25,100 TO PREDICT THE WEATHER SEVEN 5562 03:37:25,100 --> 03:37:25,567 DAYS FROM NOW. 5563 03:37:25,567 --> 03:37:28,937 SO THE SAME IS TRUE HERE. 5564 03:37:28,937 --> 03:37:30,706 BUT WE OVERALL HAD REASONABLE 5565 03:37:30,706 --> 03:37:32,240 PERFORMANCE UP TO 12 HOURS OF 5566 03:37:32,240 --> 03:37:38,113 PREDICTION IN THE FUTURE. 5567 03:37:38,113 --> 03:37:40,782 NOW OUR MODEL DIDN'T ALWAYS GET 5568 03:37:40,782 --> 03:37:42,517 IT RIGHT AND WE HAD SOME FALSE 5569 03:37:42,517 --> 03:37:43,418 POSITIVES BUT ONE INTERESTING 5570 03:37:43,418 --> 03:37:44,820 THING WE NOTED IS THAT AMONG 5571 03:37:44,820 --> 03:37:46,221 THOSE PATIENTS IN WHOM OUR 5572 03:37:46,221 --> 03:37:48,190 MODEL -- THE HIGHER THE 5573 03:37:48,190 --> 03:37:50,826 PROBABLE -- THE PROBABILITY OF 5574 03:37:50,826 --> 03:37:53,328 SEPSIS AS DESCRIBED BY THE 5575 03:37:53,328 --> 03:37:55,964 MODEL, THE HIGHER THE MORTALITY. 5576 03:37:55,964 --> 03:37:56,932 EVEN AMONG THOSE PATIENTS WHO 5577 03:37:56,932 --> 03:37:58,500 DID NOT HAVE SEPSIS. 5578 03:37:58,500 --> 03:38:00,135 AND THAT'S HIGHLIGHTED IN THAT 5579 03:38:00,135 --> 03:38:01,436 MIDDLE BAR THERE IF YOU SEE THE 5580 03:38:01,436 --> 03:38:05,707 FALSE POSITIVES, AS THE 5581 03:38:05,707 --> 03:38:06,642 PROBABILITY OF SEPSIS ACCORDING 5582 03:38:06,642 --> 03:38:10,746 TO THE MODEL INCREASED AS YOU GO 5583 03:38:10,746 --> 03:38:15,150 FROM THE MIDDLE NUMBER 8.3% TO 5584 03:38:15,150 --> 03:38:17,519 20.1%, 56.3%, THE PROBABILITY OF 5585 03:38:17,519 --> 03:38:22,124 DEATH ALSO INCREASED. 5586 03:38:22,124 --> 03:38:23,992 SO NOW SWITCHING GEARS HERE AND 5587 03:38:23,992 --> 03:38:26,728 TALKING ABOUT HOW TO PREDICT 5588 03:38:26,728 --> 03:38:28,130 SEQUELAE OF THOSE WHO ALREADY 5589 03:38:28,130 --> 03:38:29,765 HAVE SEPSIS, THIS IS ANOTHER 5590 03:38:29,765 --> 03:38:34,102 STUDY THAT HE WITH WE DID LOOKT 5591 03:38:34,102 --> 03:38:35,270 PATIENTS WHO ALREADY HAD SEPSIS 5592 03:38:35,270 --> 03:38:39,875 AND WE'RE TRYING TO PREDICT 5593 03:38:39,875 --> 03:38:41,910 THOSE WHO REQUIRE VASOPRESSORS 5594 03:38:41,910 --> 03:38:43,245 IN THE FUTURE AND CALLING THAT 5595 03:38:43,245 --> 03:38:44,146 SEPTIC SHOCK. 5596 03:38:44,146 --> 03:38:47,883 SO WE USE AGAIN A WEIBULL-COX 5597 03:38:47,883 --> 03:38:49,051 SURVIVAL MODEL BUT ADDED A 5598 03:38:49,051 --> 03:38:50,152 NEURAL NETWORK ON TOP OF THAT, 5599 03:38:50,152 --> 03:38:53,021 AND AGAIN USED ALL EMR DATA 5600 03:38:53,021 --> 03:38:54,990 USING 40 VARIABILITIES THIS TIME 5601 03:38:54,990 --> 03:39:01,229 THROUGHOUT THE ICU STAY. 5602 03:39:01,229 --> 03:39:02,898 AND AS YOU SEE THE SAME PATTERN 5603 03:39:02,898 --> 03:39:04,332 HERE, IF YOU LOOK AT THE TWO 5604 03:39:04,332 --> 03:39:06,601 LEFT PANELS, LOOKING AT THE 5605 03:39:06,601 --> 03:39:07,803 PREDICTION WINDOW AS THAT 5606 03:39:07,803 --> 03:39:08,770 PREDICTION WINDOW INCREASED, 5607 03:39:08,770 --> 03:39:12,174 BOTH THE AUC AND THE SPECIFICITY 5608 03:39:12,174 --> 03:39:14,142 DECREASED, BUT THE AUC AGAIN WAS 5609 03:39:14,142 --> 03:39:16,078 STILL PERFORMING AROUND .79. 5610 03:39:16,078 --> 03:39:17,212 NOW, LOOKING AT THE PREDICTION 5611 03:39:17,212 --> 03:39:19,514 WINDOW ON THE RIGHT, LOOKING AT 5612 03:39:19,514 --> 03:39:21,249 POSITIVE PREDICTIVE VALUE, THAT 5613 03:39:21,249 --> 03:39:22,017 ACTUALLY INCREASED AND THE 5614 03:39:22,017 --> 03:39:23,218 REASON FOR THAT IS SIMPLE, 5615 03:39:23,218 --> 03:39:25,721 BECAUSE WE USE DISCRETE TIME 5616 03:39:25,721 --> 03:39:26,521 INTERVAL PREDICTION. 5617 03:39:26,521 --> 03:39:28,056 ANYONE WHO DEVELOPED SEPTIC 5618 03:39:28,056 --> 03:39:29,691 SHOCK OR THE NEED FOR 5619 03:39:29,691 --> 03:39:30,926 VASOPRESSORS AFTER OUR WINDOW 5620 03:39:30,926 --> 03:39:33,295 WAS CONSIDERED A NEGATIVE. 5621 03:39:33,295 --> 03:39:35,597 SO AS WE INCREASE THAT LENGTH, 5622 03:39:35,597 --> 03:39:39,434 IF THE MODEL PREDICTED SEPSIS -- 5623 03:39:39,434 --> 03:39:40,669 PREDICTED SEPTIC SHOCK IN THOSE 5624 03:39:40,669 --> 03:39:41,870 PATIENTS IT WAS GOING TO IMPROVE 5625 03:39:41,870 --> 03:39:43,071 ITS ACCURACY BECAUSE THEY 5626 03:39:43,071 --> 03:39:43,839 DEVELOPED SEPTIC SHOCK WITHIN 5627 03:39:43,839 --> 03:39:50,612 THE WINDOW OF PREDICTION. 5628 03:39:50,612 --> 03:39:51,980 SO I ALSO WANT TO HIGHLIGHT THE 5629 03:39:51,980 --> 03:39:54,349 WORK OF OTHERS HERE, AND THIS 5630 03:39:54,349 --> 03:39:57,219 WORK IS PRETTY INTERESTING 5631 03:39:57,219 --> 03:39:58,920 BECAUSE THIS IS FROM THE INSIGHT 5632 03:39:58,920 --> 03:40:00,789 GROUP OUT OF THE WEST COAST. 5633 03:40:00,789 --> 03:40:02,791 THEY CREATED A MODEL TO PREDICT 5634 03:40:02,791 --> 03:40:04,426 SEPSIS USING WHAT THEY CALLED 5635 03:40:04,426 --> 03:40:05,193 EXTENDED VITALS. 5636 03:40:05,193 --> 03:40:06,695 IT'S BASICALLY JUST VITAL SIGNS 5637 03:40:06,695 --> 03:40:08,730 PLUS THE USE OF PULSE OXIMETRY 5638 03:40:08,730 --> 03:40:09,898 AS WELL AS GCS. 5639 03:40:09,898 --> 03:40:11,166 AND AS YOU CAN SEE, IT MIGHT BE 5640 03:40:11,166 --> 03:40:12,834 A LITTLE HARD TO READ, BUT ON 5641 03:40:12,834 --> 03:40:14,569 THE TOP LEFT PANEL, YOU CAN SEE 5642 03:40:14,569 --> 03:40:18,540 THE AUC ON THE Y AXIS AND THE 5643 03:40:18,540 --> 03:40:20,242 HOURS PREDICTING SEPSIS ONSET ON 5644 03:40:20,242 --> 03:40:21,276 THE X AXIS. 5645 03:40:21,276 --> 03:40:22,711 YOU SEE THAT SIMILAR TO OUR 5646 03:40:22,711 --> 03:40:24,012 MODEL, THEIR MODEL PERFORMED 5647 03:40:24,012 --> 03:40:26,081 REASONABLY WELL AND COMPARED TO 5648 03:40:26,081 --> 03:40:28,183 OTHER METRICS, PERFORMED BETTER 5649 03:40:28,183 --> 03:40:29,818 THAN THOSE METRICS AT PREDICTING 5650 03:40:29,818 --> 03:40:32,020 SEPSIS. 5651 03:40:32,020 --> 03:40:34,489 NOW, WHAT I WANT TO HIGHLIGHT AS 5652 03:40:34,489 --> 03:40:37,058 WELL, THOUGH, IS THEY TOOK THIS 5653 03:40:37,058 --> 03:40:38,994 NOT JUST USING RETROSPECTIVE 5654 03:40:38,994 --> 03:40:41,429 DATA, BUT THEN THEY APPLIED THIS 5655 03:40:41,429 --> 03:40:42,230 PROSPECTIVELY IN WHAT I BELIEVE 5656 03:40:42,230 --> 03:40:46,034 TO BE THE FIRST RCT USING A.I. 5657 03:40:46,034 --> 03:40:46,902 FOR SEPSIS CARE. 5658 03:40:46,902 --> 03:40:48,570 AND FOUND THAT THERE WAS A 5659 03:40:48,570 --> 03:40:50,972 DECREASE IN MORTALITY AS WELL AS 5660 03:40:50,972 --> 03:40:51,940 ICU LENGTH OF STAY, THE 5661 03:40:51,940 --> 03:40:53,775 MORTALITY WENT DOWN FROM 21% TO 5662 03:40:53,775 --> 03:40:55,143 9%, AND THE LENGTH OF STAY WENT 5663 03:40:55,143 --> 03:40:57,112 DOWN BY ABOUT ONE DAY. 5664 03:40:57,112 --> 03:40:59,281 AND ALSO IMPROVEMENTS IN 5665 03:40:59,281 --> 03:41:03,351 ANTIBANTIBIOTIC PRESCRIPTION, 5666 03:41:03,351 --> 03:41:04,219 ANTIBIOTICS WERE PRESCRIBED 5667 03:41:04,219 --> 03:41:04,452 EARLIER. 5668 03:41:04,452 --> 03:41:05,353 I SHOULD MENTION THE CONTROL 5669 03:41:05,353 --> 03:41:07,222 GROUP IN THIS STUDY WAS AN 5670 03:41:07,222 --> 03:41:08,290 EXISTING SEPSIS DETECTION TOOL 5671 03:41:08,290 --> 03:41:09,391 THAT THEY USED IN THEIR 5672 03:41:09,391 --> 03:41:10,692 PRACTICE. 5673 03:41:10,692 --> 03:41:12,127 SO THIS MODEL OUTPERFORMED THAT 5674 03:41:12,127 --> 03:41:15,397 SEPSIS DETECTION TOOLI TOOL. 5675 03:41:15,397 --> 03:41:16,731 SO IN OTHER WORDS, IT SEEMS THAT 5676 03:41:16,731 --> 03:41:17,599 PREDICTION OF SEPSIS CAN 5677 03:41:17,599 --> 03:41:18,900 ACTUALLY HAVE IMPROVEMENTS IN 5678 03:41:18,900 --> 03:41:24,706 OUTCOME. 5679 03:41:24,706 --> 03:41:26,141 NOW I WANT TO HIGHLIGHT A COUPLE 5680 03:41:26,141 --> 03:41:30,345 THINGS HERE. 5681 03:41:30,345 --> 03:41:31,646 SO FAR BESIDES THE EXAMPLE I 5682 03:41:31,646 --> 03:41:33,381 JUST MENTIONED EARLIER, SO FAR 5683 03:41:33,381 --> 03:41:36,551 I'VE BEEN TALKING ABOUT THINGS 5684 03:41:36,551 --> 03:41:37,986 WE SHOULD HIGHLIGHT WHEN WE'RE 5685 03:41:37,986 --> 03:41:39,087 DEVELOPING A SEPSIS PREDICTION 5686 03:41:39,087 --> 03:41:39,387 MODEL. 5687 03:41:39,387 --> 03:41:40,722 SO QUESTIONS THAT YOU WANT TO 5688 03:41:40,722 --> 03:41:42,457 ASK ARE WHAT DATA DO YOU WANT TO 5689 03:41:42,457 --> 03:41:42,757 USE? 5690 03:41:42,757 --> 03:41:45,527 SO ARE WE USING EMR DATA, ARE WE 5691 03:41:45,527 --> 03:41:47,829 USING JUST VITAL SIGNS, ARE WE 5692 03:41:47,829 --> 03:41:51,466 INCLUDING WA WAVEFORM DATA? 5693 03:41:51,466 --> 03:41:52,367 WHAT ENVIRONMENTS? 5694 03:41:52,367 --> 03:41:54,102 ARE WE PREDICTING SEPSIS OR 5695 03:41:54,102 --> 03:41:54,970 SEQUELAE IN THE EMERGENCY 5696 03:41:54,970 --> 03:41:56,404 DEPARTMENT, IN THE ICU, IN THE 5697 03:41:56,404 --> 03:41:56,771 WARDS? 5698 03:41:56,771 --> 03:41:58,039 ALL OF THOSE AREAS HAVE 5699 03:41:58,039 --> 03:41:59,474 DIFFERENT INCIDENCES OF SEPSIS 5700 03:41:59,474 --> 03:42:01,543 AND PERHAPS DIFFERENT DATA 5701 03:42:01,543 --> 03:42:03,178 AVAILABILITY. 5702 03:42:03,178 --> 03:42:04,379 WHAT SEPSIS DEFINITION ARE WE 5703 03:42:04,379 --> 03:42:05,046 USING? 5704 03:42:05,046 --> 03:42:07,015 THERE ARE TONS OF WAYS TO DEFINE 5705 03:42:07,015 --> 03:42:08,383 SEPSIS AND DEPENDING HOW YOU 5706 03:42:08,383 --> 03:42:10,085 DEFINE IT, THAT CAN AFFECT THE 5707 03:42:10,085 --> 03:42:11,586 PERFORMANCE OF YOUR MODEL, AND 5708 03:42:11,586 --> 03:42:12,621 ALSO OF COURSE WHAT MODEL DO YOU 5709 03:42:12,621 --> 03:42:16,591 WANT TO USE. 5710 03:42:16,591 --> 03:42:18,526 AS WE MOVE FROM CREATING THESE 5711 03:42:18,526 --> 03:42:20,829 MODELS, THE QUESTIONS THAT WE 5712 03:42:20,829 --> 03:42:22,931 ASK AND WERE TRYING TO DEPLOY 5713 03:42:22,931 --> 03:42:23,565 WERE VERY DIFFERENT. 5714 03:42:23,565 --> 03:42:24,566 SO A FEW QUESTIONS THAT YOU'D 5715 03:42:24,566 --> 03:42:25,800 WANT TO ASK THAT ARE RELEVANT 5716 03:42:25,800 --> 03:42:27,535 ARE, WHAT KIND OF ALERT ARE WE 5717 03:42:27,535 --> 03:42:29,838 USING? 5718 03:42:29,838 --> 03:42:32,240 SO IS IT JUST TO PREDICT A -- 5719 03:42:32,240 --> 03:42:34,075 ARE YOU JUST PREDICTING -- ARE 5720 03:42:34,075 --> 03:42:35,644 YOU CLASSIFYING WHETHER OR NOT 5721 03:42:35,644 --> 03:42:36,645 THEY'RE AT RISK OR NOT? 5722 03:42:36,645 --> 03:42:39,281 ARE YOU PROVIDING A PROBABILITY? 5723 03:42:39,281 --> 03:42:41,349 ARE YOU PROVIDING OTHER 5724 03:42:41,349 --> 03:42:43,952 ANCILLARY DATA THAT INFORMED HOW 5725 03:42:43,952 --> 03:42:45,186 THAT MODEL CAME UP WITH THAT 5726 03:42:45,186 --> 03:42:45,520 PREDICTION? 5727 03:42:45,520 --> 03:42:47,589 SO CALLED EXPLAINABLE A.I.? 5728 03:42:47,589 --> 03:42:49,324 AND THEN WHAT DEPLOYMENT 5729 03:42:49,324 --> 03:42:49,591 STRATEGY? 5730 03:42:49,591 --> 03:42:50,825 SO THE IMPLEMENTATION PIPELINE 5731 03:42:50,825 --> 03:42:51,526 IS IMPORTANT. 5732 03:42:51,526 --> 03:42:52,994 THIS IS THINGS ON THE BACK END. 5733 03:42:52,994 --> 03:42:55,497 SO HOW ARE WE ENSURING PATIENT 5734 03:42:55,497 --> 03:42:55,964 PRIVACY, FOR INSTANCE? 5735 03:42:55,964 --> 03:42:58,133 HOW ARE WE ENSURING THAT THE 5736 03:42:58,133 --> 03:42:59,968 MODEL IS BEING USED IN AN 5737 03:42:59,968 --> 03:43:01,069 EFFICIENT WAY ON THE BACK END? 5738 03:43:01,069 --> 03:43:03,171 AND ALSO WHAT DOES THAT END USER 5739 03:43:03,171 --> 03:43:03,471 EXPERIENCE? 5740 03:43:03,471 --> 03:43:06,041 WHAT ARE HE TH THEY ACTUALLY SEG 5741 03:43:06,041 --> 03:43:07,342 AND HOW IS THAT DATA BEING 5742 03:43:07,342 --> 03:43:08,209 PRESENTED TO THEM? 5743 03:43:08,209 --> 03:43:09,744 WHAT OUTCOME ARE WE LOOKING AT? 5744 03:43:09,744 --> 03:43:14,149 ARE WE LOOKING AT IMPROVEMENTS 5745 03:43:14,149 --> 03:43:19,287 IN STEP ONE BUNDLE COMPLIANCE 5746 03:43:19,287 --> 03:43:20,922 OR -- THEN WHAT ACTION SPHWH 5747 03:43:20,922 --> 03:43:24,659 J?WE HAVE TO MAKE SURE THAT'S TE 5748 03:43:24,659 --> 03:43:27,896 CASE. 5749 03:43:27,896 --> 03:43:29,097 SO I'M GOING TO TALK ABOUT A 5750 03:43:29,097 --> 03:43:31,666 COUPLE OF CASE STUDIES HERE AND 5751 03:43:31,666 --> 03:43:32,300 IMPLEMENTATION. 5752 03:43:32,300 --> 03:43:34,869 THIS WAS THE EWS MODEL OUT OF U 5753 03:43:34,869 --> 03:43:35,170 PENICILLIN. 5754 03:43:35,170 --> 03:43:43,611 SU -- U-PENN. 5755 03:43:43,611 --> 03:43:46,915 PERFORMANCE WAS GOOD, REALLY 5756 03:43:46,915 --> 03:43:49,084 WHAT THEY ONLY FOUND WAS THAT 5757 03:43:49,084 --> 03:43:54,889 3.7% INCREASE IN SERUM 5758 03:43:54,889 --> 03:43:55,557 LACTATE -- PRESCRIPTION. 5759 03:43:55,557 --> 03:43:57,192 WHEN THEY USE THIS MODEL TO 5760 03:43:57,192 --> 03:43:58,493 ACTUALLY DETECT SEPSIS, THEY 5761 03:43:58,493 --> 03:44:00,829 FOUND A MUCH MORE ROBUST 5762 03:44:00,829 --> 03:44:01,696 RESPONSE BY PATIENTS. 5763 03:44:01,696 --> 03:44:03,331 OR BY CLINICIANS. 5764 03:44:03,331 --> 03:44:07,502 SO THEY WERE IMPROVING LACTATE 5765 03:44:07,502 --> 03:44:08,470 ORDERS, ANTIBIOTIC PRESCRIPTION 5766 03:44:08,470 --> 03:44:09,137 WAS EARLIER. 5767 03:44:09,137 --> 03:44:10,472 SO WHAT THIS SAYS IS, JUST 5768 03:44:10,472 --> 03:44:11,806 BECAUSE WE PREDICT SOMETHING 5769 03:44:11,806 --> 03:44:13,008 DOESN'T MEAN THAT CLINICIANS ARE 5770 03:44:13,008 --> 03:44:13,975 GOING TO ACT ON IT BECAUSE IT 5771 03:44:13,975 --> 03:44:16,177 MAY NOT BE SOMETHING THAT'S 5772 03:44:16,177 --> 03:44:17,379 IMMEDIATELY OBVIOUS TO THEM, 5773 03:44:17,379 --> 03:44:18,480 THEY MAY NOT ACTUALLY DO 5774 03:44:18,480 --> 03:44:19,247 ANYTHING ABOUT IT. 5775 03:44:19,247 --> 03:44:21,116 SO THESE ARE VERY IMPORTANT 5776 03:44:21,116 --> 03:44:22,617 CONSIDERATIONS WE HAVE TO MAKE 5777 03:44:22,617 --> 03:44:24,619 AS WE'RE TRYING TO MOVE FROM 5778 03:44:24,619 --> 03:44:28,857 CREATION TO DEPLOYMENT. 5779 03:44:28,857 --> 03:44:31,526 SO ANOTHER EXAMPLE, VERY 5780 03:44:31,526 --> 03:44:36,664 DIFFERENT EXAMPLE WAS THE TREWS 5781 03:44:36,664 --> 03:44:38,967 SCORE, OUT OF HOPKINS. 5782 03:44:38,967 --> 03:44:41,136 SO MODEL PERFORMANCE WAS PRETTY 5783 03:44:41,136 --> 03:44:42,370 SIMILAR, SENSITIVITY WAS PERHAPS 5784 03:44:42,370 --> 03:44:43,138 BETTER. 5785 03:44:43,138 --> 03:44:45,073 THEY PROSPECTIVELY STUDIED THIS 5786 03:44:45,073 --> 03:44:46,875 IN SEVEN HOSPITALS AND FOUND A 5787 03:44:46,875 --> 03:44:48,743 MUCH MORE ROBUST RESPONSE. 5788 03:44:48,743 --> 03:44:50,045 SO IN OTHER WORDS, THE UPTAKE 5789 03:44:50,045 --> 03:44:55,650 WAS MUCH HIGHER. 5790 03:44:55,650 --> 03:44:58,586 WHY MIGHT THAT BE? 5791 03:44:58,586 --> 03:45:00,355 WELL, A LOT OF THIS HAD TO DO 5792 03:45:00,355 --> 03:45:02,524 WITH HOW THE DATA WAS PRESENTED. 5793 03:45:02,524 --> 03:45:05,393 SO IT WAS -- THE TREWS SCORE 5794 03:45:05,393 --> 03:45:06,828 MODEL THEY CREATED WAS 5795 03:45:06,828 --> 03:45:08,163 INTEGRATED WITHIN THEIR 5796 03:45:08,163 --> 03:45:09,230 WORKFLOW, SO AS YOU CAN SEE HERE 5797 03:45:09,230 --> 03:45:11,866 AS AN EXAMPLE HERE, THIS WAS AN 5798 03:45:11,866 --> 03:45:13,334 EXAMPLE OF ONE OF THE POP-UPS. 5799 03:45:13,334 --> 03:45:14,702 IF YOU NOTICE IT LOOKS VERY 5800 03:45:14,702 --> 03:45:15,470 SIMILAR TO SOME OF THE 5801 03:45:15,470 --> 03:45:16,838 CHECKLISTS THAT ARE FAMILIAR TO 5802 03:45:16,838 --> 03:45:19,541 A LOT OF CLINICIANS AND ALSO IT 5803 03:45:19,541 --> 03:45:20,408 WAS EXPLAINABLE. 5804 03:45:20,408 --> 03:45:22,377 ON THE BOTTOM IT SHOWS WHAT ARE 5805 03:45:22,377 --> 03:45:24,079 THE THINGS DRIVING THE PREDEXES? 5806 03:45:24,079 --> 03:45:25,847 THE CREATININE WAS HIGHER, THE 5807 03:45:25,847 --> 03:45:27,015 LACTATE WAS GOING UP. 5808 03:45:27,015 --> 03:45:28,817 AND IT SERVED A SPECIFIC NEED, 5809 03:45:28,817 --> 03:45:33,088 MEANING IT HAD TO HAVE 5810 03:45:33,088 --> 03:45:33,721 SEP-1 BUNDLE COMPLIANCE. 5811 03:45:33,721 --> 03:45:36,024 SO WE HAVE TO MAKE IT SOMETHING 5812 03:45:36,024 --> 03:45:39,561 USEFUL FOR THE END USERS. 5813 03:45:39,561 --> 03:45:41,096 AND THEN -- SO I WANT TO TALK A 5814 03:45:41,096 --> 03:45:43,264 LIT ABOUT BARRIERS TO WIDESPREAD 5815 03:45:43,264 --> 03:45:46,801 ADAPTATION OF THESE MODELS. 5816 03:45:46,801 --> 03:45:49,537 I'M GOING TO HIGHLIGHT THREE. 5817 03:45:49,537 --> 03:45:50,405 SO ONE IS DISTRUST. 5818 03:45:50,405 --> 03:45:51,639 SO JUST BECAUSE WE HAVE 5819 03:45:51,639 --> 03:45:52,707 SOMETHING THAT'S PRESENTED TO US 5820 03:45:52,707 --> 03:45:54,142 DOESN'T MEAN THAT WE BELIEVE IT 5821 03:45:54,142 --> 03:45:56,778 AS CLINICIANS. 5822 03:45:56,778 --> 03:45:58,880 SO I WANT TO -- IF YOU CAN HIT 5823 03:45:58,880 --> 03:46:01,382 NEXT, PLEASE. 5824 03:46:01,382 --> 03:46:03,885 NOW WHAT I WANT TO HIGHLIGHT IS 5825 03:46:03,885 --> 03:46:04,919 IT ONE ASPECT OF THE ACE MODEL 5826 03:46:04,919 --> 03:46:06,354 THAT WE CREATED IS 5827 03:46:06,354 --> 03:46:06,855 EXPLAINABILITY. 5828 03:46:06,855 --> 03:46:08,990 SO YOU CAN SEE THE AREA THAT'S 5829 03:46:08,990 --> 03:46:10,458 CIRCLED ON THE BOTTOM SHOWS ALL 5830 03:46:10,458 --> 03:46:12,360 OF THE VARIABLES THAT ARE 5831 03:46:12,360 --> 03:46:13,962 DRIVING THE PREDICTIONS SO THAT 5832 03:46:13,962 --> 03:46:15,430 CLINICIANS CAN KNOW WHETHER OR 5833 03:46:15,430 --> 03:46:16,764 NOT THEY CAN TRUST THE 5834 03:46:16,764 --> 03:46:17,799 PREDICTIONS THAT ARE BEING MADE 5835 03:46:17,799 --> 03:46:19,501 OR IF THEY THINK THEY MAY BE 5836 03:46:19,501 --> 03:46:22,504 SPEUR JUST. 5837 03:46:22,504 --> 03:46:24,139 THE NEXT ISSUE IS 5838 03:46:24,139 --> 03:46:24,672 GENERALIZABILITY. 5839 03:46:24,672 --> 03:46:26,441 SO JUST BECAUSE IT WORKS AT SITE 5840 03:46:26,441 --> 03:46:27,942 A DOESN'T NECESSARILY MEAN IT 5841 03:46:27,942 --> 03:46:30,311 WILL WORK IN SIGHT D. 5842 03:46:30,311 --> 03:46:32,280 SO PART OF THE SECOND STUDY THAT 5843 03:46:32,280 --> 03:46:34,449 I MENTIONED WITH PREDICTING 5844 03:46:34,449 --> 03:46:35,884 SEPTIC SHOCK WAS THIS USE OF 5845 03:46:35,884 --> 03:46:36,451 TRANSFER LEARNING. 5846 03:46:36,451 --> 03:46:38,686 THAT IS WE TRAIN A MODEL AT ONE 5847 03:46:38,686 --> 03:46:40,221 SITE, USE THAT SAME MODEL AT A 5848 03:46:40,221 --> 03:46:41,723 DIFFERENT SITE, AND SIMPLY TWEAK 5849 03:46:41,723 --> 03:46:44,125 IT USING A SUBSET OF PATIENT 5850 03:46:44,125 --> 03:46:45,660 DATA, AND, THEREFORE, THE MODEL 5851 03:46:45,660 --> 03:46:46,761 PREDICTION WAS MORE ACCURATE. 5852 03:46:46,761 --> 03:46:48,630 AND THAT'S WHAT WE FOUND IN OUR 5853 03:46:48,630 --> 03:46:48,830 STUDY. 5854 03:46:48,830 --> 03:46:50,932 SO THIS IS BEING USED MORE, THIS 5855 03:46:50,932 --> 03:46:54,135 IS ACTUALLY BEING USED A BIT IN 5856 03:46:54,135 --> 03:46:56,004 THE SECOND VERSION OF THE EPIC 5857 03:46:56,004 --> 03:46:57,405 SEPSIS PREDICTION MODEL. 5858 03:46:57,405 --> 03:47:00,308 SO THIS CONCEPT CAN HELP WITH 5859 03:47:00,308 --> 03:47:01,609 GENERALIZABILITY. 5860 03:47:01,609 --> 03:47:04,979 SO THE OTHER ISSUE IS ALARM 5861 03:47:04,979 --> 03:47:05,313 FATIGUE. 5862 03:47:05,313 --> 03:47:06,648 I'M GOING TO HIGHLIGHT SOME WORK 5863 03:47:06,648 --> 03:47:09,951 THAT WAS DONE AGAIN BY MY 5864 03:47:09,951 --> 03:47:14,522 COLLEAGUE NEMATI IN HIS 5865 03:47:14,522 --> 03:47:15,190 CONFORMER ALGORITHM. 5866 03:47:15,190 --> 03:47:16,524 WHAT THIS MODEL BASICALLY DOES 5867 03:47:16,524 --> 03:47:19,594 IS SAY "I DON'T KNOW." 5868 03:47:19,594 --> 03:47:20,595 SO IF -- IN OTHER WORDS, IT'S 5869 03:47:20,595 --> 03:47:22,330 NOT BEING FORCED TO MAKE A 5870 03:47:22,330 --> 03:47:24,132 DECISION ONE WAY OR THE OTHER 5871 03:47:24,132 --> 03:47:27,835 BASED ON THE OUTPUT IT HAS, IT'S 5872 03:47:27,835 --> 03:47:29,070 ALLOWING THAT ROOM TO SHOW, YOU 5873 03:47:29,070 --> 03:47:31,806 KNOW WHAT, I'D RATHER NOT MAKE A 5874 03:47:31,806 --> 03:47:32,907 PREDICTION BECAUSE IT MIGHT NOT 5875 03:47:32,907 --> 03:47:34,909 BE ACCURATE AND USE YOUR BEST 5876 03:47:34,909 --> 03:47:35,877 JUDGMENT OR PERHAPS ORDER MORE 5877 03:47:35,877 --> 03:47:37,645 TESTS TO IMPROVE MY ACCURACY AND 5878 03:47:37,645 --> 03:47:38,947 MY PERFORMANCE. 5879 03:47:38,947 --> 03:47:41,082 SO ANOTHER ISSUE THAT I'LL 5880 03:47:41,082 --> 03:47:44,118 HIGHLIGHT IS BIAS. 5881 03:47:44,118 --> 03:47:45,653 AND THE FACT THAT SIMILAR TO THE 5882 03:47:45,653 --> 03:47:47,121 GENERALIZABILITY ISSUE, IF THERE 5883 03:47:47,121 --> 03:47:48,656 ARE PATIENTS IN WHOM YOUR MODEL 5884 03:47:48,656 --> 03:47:51,326 MAY NOT HAVE BEEN EXPOSED TO AND 5885 03:47:51,326 --> 03:47:53,628 YOU TRY TO MAKE PREDICTIONS ON 5886 03:47:53,628 --> 03:47:55,129 THEM, THOSE MODELS MAY BE WRONG. 5887 03:47:55,129 --> 03:47:56,364 SO THERE ARE A LOT OF DIFFERENT 5888 03:47:56,364 --> 03:47:57,899 WAYS THAT WE CAN TRY TO 5889 03:47:57,899 --> 03:47:59,100 POTENTIALLY SOLVE THAT PROBLEM 5890 03:47:59,100 --> 03:48:00,301 AND SOME OF THEM ARE LISTED 5891 03:48:00,301 --> 03:48:05,139 THERE. 5892 03:48:05,139 --> 03:48:06,407 >> ONE MINUTE REMAINING. 5893 03:48:06,407 --> 03:48:07,075 THANK YOU. 5894 03:48:07,075 --> 03:48:07,475 >> THANK YOU. 5895 03:48:07,475 --> 03:48:10,845 SO ON THE HORIZON I THINK IS THE 5896 03:48:10,845 --> 03:48:12,180 USE OF GEN A.I. 5897 03:48:12,180 --> 03:48:13,414 I'M NOT GOING TO TOUCH TOO MUCH 5898 03:48:13,414 --> 03:48:14,782 ON THIS BUT WANT TO HIGHLIGHT 5899 03:48:14,782 --> 03:48:16,618 ONE STUDY THAT CAME OUT VERY 5900 03:48:16,618 --> 03:48:20,555 RECENTLY LOOKING AT PREDICTION 5901 03:48:20,555 --> 03:48:24,259 OF FUTURE -- PREDICTION OF 5902 03:48:24,259 --> 03:48:25,026 FUTURE PANDEMICS. 5903 03:48:25,026 --> 03:48:27,128 SO THIS MODEL ACTUALLY SEEMED TO 5904 03:48:27,128 --> 03:48:29,664 DO PRETTY WELL AT PREDICTING 5905 03:48:29,664 --> 03:48:31,966 FUTURE PANDEMICS BASED ON 5906 03:48:31,966 --> 03:48:33,167 DIFFERENCES IN THE DATA 5907 03:48:33,167 --> 03:48:34,202 DISTRIBUTIONS WITHIN THE 5908 03:48:34,202 --> 03:48:39,307 PATIENTS IN WHOM IT WAS EXPOSED. 5909 03:48:39,307 --> 03:48:41,409 SO IN SUMMARY, SEPSIS PREDICTION 5910 03:48:41,409 --> 03:48:43,511 AND PROGNOSIS IS POSSIBLE USING 5911 03:48:43,511 --> 03:48:44,946 A.I. TOOLS AND CAN HAVE 5912 03:48:44,946 --> 03:48:46,014 CLINICALLY MEANINGFUL OUTCOMES. 5913 03:48:46,014 --> 03:48:48,950 THERE ARE CHALLENGES, 5914 03:48:48,950 --> 03:48:50,285 SPECIFICALLY DISTRUST, 5915 03:48:50,285 --> 03:48:51,152 GENERALIZABILITY, ALARM FATIGUE 5916 03:48:51,152 --> 03:48:52,920 AND BIAS, BUT THERE ARE 5917 03:48:52,920 --> 03:48:53,788 POTENTIALLY WAYS AROUND THAT 5918 03:48:53,788 --> 03:48:54,922 THAT HOPEFULLY WILL BE 5919 03:48:54,922 --> 03:48:55,790 INTEGRATED AND WORK IN THE 5920 03:48:55,790 --> 03:48:56,224 FUTURE. 5921 03:48:56,224 --> 03:48:58,526 AND FUTURE DIRECTIONS, BESIDES 5922 03:48:58,526 --> 03:48:59,861 THAT DEALING WITH THOSE 5923 03:48:59,861 --> 03:49:01,929 CHALLENGES, COULD POTENTIALLY 5924 03:49:01,929 --> 03:49:03,698 INVOLVE DEPLOYMENT STRATEGIES 5925 03:49:03,698 --> 03:49:05,867 THAT IMPROVE GENERALIZABILITY 5926 03:49:05,867 --> 03:49:07,535 AND ACCEPTANCE AND INTEGRATION 5927 03:49:07,535 --> 03:49:09,537 INTO WORKFLOWS THAT WILL 5928 03:49:09,537 --> 03:49:10,938 HOPEFULLY MAKE THESE MODELS MORE 5929 03:49:10,938 --> 03:49:12,307 ACTIONABLE AND IMPROVE PATIENT 5930 03:49:12,307 --> 03:49:12,573 OUTCOMES. 5931 03:49:12,573 --> 03:49:13,541 AND WITH THAT, I THANK YOU VERY 5932 03:49:13,541 --> 03:49:14,509 MUCH FOR YOUR TIME. 5933 03:49:14,509 --> 03:49:16,110 >> THANK YOU, DR. HOLDER. 5934 03:49:16,110 --> 03:49:19,781 WE HAVE TIME MAYBE FOR ONE 5935 03:49:19,781 --> 03:49:20,648 QUESTION. 5936 03:49:20,648 --> 03:49:21,849 FOLKS CAN GO AHEAD AND RAISE 5937 03:49:21,849 --> 03:49:25,119 THEIR HANDS IF THEY HAVE A 5938 03:49:25,119 --> 03:49:34,696 QUESTION. 5939 03:49:34,696 --> 03:49:35,063 DR. KOUTROULIS. 5940 03:49:35,063 --> 03:49:36,364 >> THANK YOU FOR THIS GREAT 5941 03:49:36,364 --> 03:49:36,698 PRESENTATION. 5942 03:49:36,698 --> 03:49:38,399 YOU MENTIONED BRIEFLY ABOUT THIS 5943 03:49:38,399 --> 03:49:40,268 SEPSIS DEFINITION THAT CAN BE 5944 03:49:40,268 --> 03:49:41,602 USED IN THOSE MODEL, AND THAT 5945 03:49:41,602 --> 03:49:42,470 CAN VARY. 5946 03:49:42,470 --> 03:49:44,072 AGAIN, WE TALKED BEFORE IN THE 5947 03:49:44,072 --> 03:49:48,176 PREVIOUS TALKS ABOUT HOW THE 5948 03:49:48,176 --> 03:49:49,077 DEFINITION HAS CHANGED. 5949 03:49:49,077 --> 03:49:54,449 WHAT ARE YOUR THOUGHTS ABOUT 5950 03:49:54,449 --> 03:49:59,387 WHAT TO USE, ACCEP SEPSIS 2, SE, 5951 03:49:59,387 --> 03:50:00,621 OR EVEN CLINICAL JUDGMENT HERE 5952 03:50:00,621 --> 03:50:02,323 AND THE ICD10 CODE, WHICH WE 5953 03:50:02,323 --> 03:50:03,591 KNOW IS NOT A PERFECT WAY TO DO 5954 03:50:03,591 --> 03:50:04,058 IT. 5955 03:50:04,058 --> 03:50:05,760 WHAT ARE YOUR THOUGHTS ON THAT? 5956 03:50:05,760 --> 03:50:06,794 >> THAT'S A GREAT QUESTION AND I 5957 03:50:06,794 --> 03:50:08,463 THINK IT'S A VERY LOADED ONE AND 5958 03:50:08,463 --> 03:50:10,765 VERY HOTLY DEBATED. 5959 03:50:10,765 --> 03:50:14,335 I THINK A LOT OF IT DPSH I WILL 5960 03:50:14,335 --> 03:50:15,570 TELL YOU A LOT OF THE STUDIES 5961 03:50:15,570 --> 03:50:16,904 THAT HAVE DONE WORK IN SEPSIS 5962 03:50:16,904 --> 03:50:20,074 PREDICTION INCLUDING OURS USE 5963 03:50:20,074 --> 03:50:22,810 SEPSIS 3. 5964 03:50:22,810 --> 03:50:25,113 NOW, OF COURSE SEPSIS 3 IS 5965 03:50:25,113 --> 03:50:26,414 PROBABLY A -- THERE'S A LOT OF 5966 03:50:26,414 --> 03:50:27,682 DEBATE ABOUT WHICH ONE IS 5967 03:50:27,682 --> 03:50:27,915 BETTER. 5968 03:50:27,915 --> 03:50:29,083 I THINK IT DEPENDS ON WHAT 5969 03:50:29,083 --> 03:50:30,818 YOU'RE TRYING TO DO. 5970 03:50:30,818 --> 03:50:34,756 SO AS AN EXAMPLE, IF YOU'RE 5971 03:50:34,756 --> 03:50:38,092 FOCUSED ON SEP-1 COMPLIANCE, 5972 03:50:38,092 --> 03:50:39,827 SEP-1 DOES NOT REALLY TAKE -- IT 5973 03:50:39,827 --> 03:50:40,962 DOESN'T USE SEPSIS 3. 5974 03:50:40,962 --> 03:50:41,929 THERE ARE OTHER DEFINITIONS AS 5975 03:50:41,929 --> 03:50:42,263 WELL. 5976 03:50:42,263 --> 03:50:43,631 THERE'S THE CDC DEFINITION, ET 5977 03:50:43,631 --> 03:50:44,565 CETERA. 5978 03:50:44,565 --> 03:50:46,634 A LOT OF IT REALLY DEPENDS ON 5979 03:50:46,634 --> 03:50:47,902 THE DATA THAT YOU'RE USING AND 5980 03:50:47,902 --> 03:50:48,870 WHAT YOU'RE TRYING TO DO WITH 5981 03:50:48,870 --> 03:50:49,203 IT. 5982 03:50:49,203 --> 03:50:50,738 FOR US, WE WANTED TO MAKE THIS 5983 03:50:50,738 --> 03:50:51,873 AS CLINICALLY MEANINGFUL AS 5984 03:50:51,873 --> 03:50:52,940 POSSIBLE, SO WE DIDN'T 5985 03:50:52,940 --> 03:50:56,244 NECESSARILY WANT TO USE ICD-10 5986 03:50:56,244 --> 03:50:56,444 CODES. 5987 03:50:56,444 --> 03:50:59,747 AND OF COURSE WE KNOW THE ISSUES 5988 03:50:59,747 --> 03:51:01,516 WITH OVERDIAGNOSIS OF SEPSIS 5989 03:51:01,516 --> 03:51:05,286 SINCE THE PURPOSE OF THAT IS FOR 5990 03:51:05,286 --> 03:51:05,520 BILLING. 5991 03:51:05,520 --> 03:51:07,155 I THINK THAT ANY WAY THAT YOU 5992 03:51:07,155 --> 03:51:10,091 CAN BEST OPERATIONALIZE IT BASED 5993 03:51:10,091 --> 03:51:13,294 OON YOUR DATA, WHAT YOU HAVE 5994 03:51:13,294 --> 03:51:14,929 AVAILABLE TO YOU AND WHAT YOU 5995 03:51:14,929 --> 03:51:16,731 WANT TO DO WITH IT IS HELPFUL. 5996 03:51:16,731 --> 03:51:18,900 MY PERSONAL BIAS WAS TO MAKE 5997 03:51:18,900 --> 03:51:20,668 THIS AS ACTUAL AS POSSIBLE AND 5998 03:51:20,668 --> 03:51:22,637 ALSO TO USE WAYS OF IDENTIFYING 5999 03:51:22,637 --> 03:51:23,771 SEPSIS THAT HAVE ALREADY BEEN 6000 03:51:23,771 --> 03:51:24,205 VALIDATED. 6001 03:51:24,205 --> 03:51:25,706 SO FOR INSTANCE, IN OUR STUDY, 6002 03:51:25,706 --> 03:51:29,610 IN OUR STUDIES, WE USED SEPSIS 6003 03:51:29,610 --> 03:51:36,684 3, USING THE WAY THAT CHRIS SEE 6004 03:51:36,684 --> 03:51:40,221 SEYMOUR'S GROUP USED IT FOR 6005 03:51:40,221 --> 03:51:41,322 THEIR VALIDATION PAPER A FEW 6006 03:51:41,322 --> 03:51:43,391 YEARS BACK. 6007 03:51:43,391 --> 03:51:44,926 SO AS WELL AS MAKING IT SEEM A 6008 03:51:44,926 --> 03:51:46,060 LITTLE MORE ACTIONABLE FOR 6009 03:51:46,060 --> 03:51:46,360 CLINICIANS. 6010 03:51:46,360 --> 03:51:46,828 >> FANTASTIC. 6011 03:51:46,828 --> 03:51:48,663 THANK YOU, DR. HOLDER, FOR AN 6012 03:51:48,663 --> 03:51:53,100 EXCELLENT KICKO KICKOFF AND OVEW 6013 03:51:53,100 --> 03:51:53,968 OF WHAT THE OPPORTUNITIES ARE. 6014 03:51:53,968 --> 03:51:55,503 BECAUSE YOU TOUCHED ON KIND OF 6015 03:51:55,503 --> 03:51:56,704 CHALLENGES IN IMPLEMENTATION AND 6016 03:51:56,704 --> 03:51:58,473 WHAT IS ACTIONABLE, WE'RE GOING 6017 03:51:58,473 --> 03:52:01,242 TO BE NEXT JOINED BY DR. CARA 6018 03:52:01,242 --> 03:52:03,845 O'BRIEN, WHO IS FROM DUKE 6019 03:52:03,845 --> 03:52:05,313 UNIVERSITY, AND HAS A LOT OF 6020 03:52:05,313 --> 03:52:07,515 EXPERIENCE IN THIS DOMAIN, AND 6021 03:52:07,515 --> 03:52:09,917 SHE'S GOING TO SPEAK ON TOWARDS 6022 03:52:09,917 --> 03:52:11,285 AUGMENTED INTELLIGENCE: 6023 03:52:11,285 --> 03:52:12,820 EFFECTIVE INTEGRATION OF SEPSIS 6024 03:52:12,820 --> 03:52:17,525 A.I. AT THE BEDSIDE. 6025 03:52:17,525 --> 03:52:17,825 DR. O'BRIEN? 6026 03:52:17,825 --> 03:52:19,994 >> THANK YOU VERY MUCH, DR. LIU. 6027 03:52:19,994 --> 03:52:21,262 I THINK THERE'S SIGNIFICANT 6028 03:52:21,262 --> 03:52:22,029 OVERLAP BETWEEN WHAT I'M GOING 6029 03:52:22,029 --> 03:52:23,598 TO TALK ABOUT AND WHAT 6030 03:52:23,598 --> 03:52:24,632 DR. HOLDER JUST COVERED, BUT I 6031 03:52:24,632 --> 03:52:25,800 LOVE THE FACT THAT HE 6032 03:52:25,800 --> 03:52:28,002 HIGHLIGHTED AT THE END SEAMLESS 6033 03:52:28,002 --> 03:52:28,336 INTEGRATION. 6034 03:52:28,336 --> 03:52:29,403 WE'RE GOING TO SPEND SOME TIME 6035 03:52:29,403 --> 03:52:30,705 AT THE END TALKING ABOUT WHY I 6036 03:52:30,705 --> 03:52:31,873 THINK THAT'S PROBABLY ONE OF THE 6037 03:52:31,873 --> 03:52:34,075 MOST IMPORTANT ASPECTS OF 6038 03:52:34,075 --> 03:52:36,511 AUGMENTED INTELLIGENCE 6039 03:52:36,511 --> 03:52:37,311 IMPLEMENTATION FOR SEPSIS. 6040 03:52:37,311 --> 03:52:41,115 YOU CAN HAVE THE PERFECT A.I. 6041 03:52:41,115 --> 03:52:42,083 MODEL BUT IF IT'S NOT 6042 03:52:42,083 --> 03:52:43,885 IMPLEMENTED IN A WAY THAT HAS 6043 03:52:43,885 --> 03:52:44,986 IMPACT FOR PATIENTS THEN IT'S A 6044 03:52:44,986 --> 03:52:48,256 USELESS MODEL. 6045 03:52:48,256 --> 03:52:49,724 JUST TO BACK UP A MINUTE, I KNOW 6046 03:52:49,724 --> 03:52:51,826 THIS HAS BEEN COVERED IN SEVERAL 6047 03:52:51,826 --> 03:52:52,460 PRESENTATIONS ALREADY BUT I 6048 03:52:52,460 --> 03:52:54,028 REALLY THINK THE PREVALENCE AND 6049 03:52:54,028 --> 03:52:57,064 SEVERITY OF SEPSIS ARE WHAT 6050 03:52:57,064 --> 03:52:59,066 MAKES IT MOST CONDUCIVE FOR A.I. 6051 03:52:59,066 --> 03:52:59,433 IMPLEMENTATION. 6052 03:52:59,433 --> 03:53:02,570 SO BECAUSE IT'S EXCEEDINGLY 6053 03:53:02,570 --> 03:53:03,771 COMMON IMPACTING PATIENTS ACROSS 6054 03:53:03,771 --> 03:53:05,339 THE U.S. ALONE, HAS A HIGH RATE 6055 03:53:05,339 --> 03:53:07,308 OF MORTALITY, BUT HAS TREATMENTS 6056 03:53:07,308 --> 03:53:10,845 THAT HAVE BEEN SHOWN TO IMPACT 6057 03:53:10,845 --> 03:53:14,482 PATIENT OUTCOMES, IT'S AN IDEAL 6058 03:53:14,482 --> 03:53:15,449 DISEASE TO PREDICT. 6059 03:53:15,449 --> 03:53:16,784 HOWEVER IT'S EXTREMELY 6060 03:53:16,784 --> 03:53:17,451 CHALLENGING TO DIAGNOSE. 6061 03:53:17,451 --> 03:53:19,086 THE SIGNS AND SYMPTOMS ARE VAGUE 6062 03:53:19,086 --> 03:53:20,087 AND OVERLAP WITH MANY OTHER 6063 03:53:20,087 --> 03:53:20,555 DISEASES. 6064 03:53:20,555 --> 03:53:22,323 SO THERE'S A HIGH LEVEL OF 6065 03:53:22,323 --> 03:53:23,391 CLINICAL SUSPICION AND JUDGMENT 6066 03:53:23,391 --> 03:53:24,492 REQUIRED IN ORDER TO MAKE THE 6067 03:53:24,492 --> 03:53:27,228 DIAGNOSIS. 6068 03:53:27,228 --> 03:53:29,897 I THINK LASTLY, SEPSIS LIKELY 6069 03:53:29,897 --> 03:53:30,765 INCORPORATES MANY SUBTYPES OF 6070 03:53:30,765 --> 03:53:32,533 ILLNESS IN DIFFERENT POPULATIONS 6071 03:53:32,533 --> 03:53:35,570 OF PATIENTS LIKELY HAVE 6072 03:53:35,570 --> 03:53:38,005 DIFFERENT DISEASE -- AND MAY BE 6073 03:53:38,005 --> 03:53:39,006 IMPACTED DIFFERENTLY BY 6074 03:53:39,006 --> 03:53:42,944 TREATMENT. 6075 03:53:42,944 --> 03:53:43,811 SO WHAT'S THE SPECIFIC 6076 03:53:43,811 --> 03:53:44,812 OPPORTUNITY FOR A.I. IN SEPSIS? 6077 03:53:44,812 --> 03:53:47,148 I THINK NOW THAT WE HAVE ALMOST 6078 03:53:47,148 --> 03:53:48,683 UNIVERSAL DEPLOYMENT OF 6079 03:53:48,683 --> 03:53:49,917 ELECTRONIC HEALTH RECORD SYSTEMS 6080 03:53:49,917 --> 03:53:51,652 AS WELL AS BEDSIDE MONITORS THAT 6081 03:53:51,652 --> 03:53:53,721 ARE RECORDING CONTINUOUS VITAL 6082 03:53:53,721 --> 03:53:55,590 SIGNS, WE'RE CAPTURING JUST AN 6083 03:53:55,590 --> 03:53:57,024 ENORMOUS AMOUNT OF DATA, OFTEN 6084 03:53:57,024 --> 03:53:59,627 IN A CONTINUOUS FASHION. 6085 03:53:59,627 --> 03:54:00,895 I'M A BUSY HOSPITALIST. 6086 03:54:00,895 --> 03:54:03,097 I MAY LOOK AT A PATIENT'S VITAL 6087 03:54:03,097 --> 03:54:05,433 SIGNS IN THE COMPUTER, MAYBE TWO 6088 03:54:05,433 --> 03:54:06,534 TO THREE TIMES A DAY BUT 6089 03:54:06,534 --> 03:54:07,969 CERTAINLY NOT CONTINUOUSLY. 6090 03:54:07,969 --> 03:54:10,571 THESE A.I. TOOLS ARE CAPABLE OF 6091 03:54:10,571 --> 03:54:13,641 ANALYZING LARGE SETS OF DATA IN 6092 03:54:13,641 --> 03:54:16,143 NEAR REALTIME. 6093 03:54:16,143 --> 03:54:19,780 RECOGNIZING RELATIONSHIPS OF 6094 03:54:19,780 --> 03:54:20,481 DISEASE PRESENTATION THAT WE 6095 03:54:20,481 --> 03:54:22,350 WOULDN'T BE ABLE TO RECOGNIZE AS 6096 03:54:22,350 --> 03:54:22,883 HUMANS. 6097 03:54:22,883 --> 03:54:25,052 THESE SUBTLE PATTERNS CAN BE 6098 03:54:25,052 --> 03:54:28,356 INDICATIVE OF EARLY SEPSIS OR 6099 03:54:28,356 --> 03:54:29,390 HIGH RISK PATIENTS 6100 03:54:29,390 --> 03:54:30,691 POTENTIALLY -- ADDITIONALLY, 6101 03:54:30,691 --> 03:54:31,792 FEATURE ENGINEERING WHICH IS A 6102 03:54:31,792 --> 03:54:33,060 KEY COMPONENT OF MANY MACHINE 6103 03:54:33,060 --> 03:54:34,929 LEARNING MODELS CAN ENHANCE 6104 03:54:34,929 --> 03:54:36,230 A.I.'S ABILITY TO DETECT SEPSIS 6105 03:54:36,230 --> 03:54:37,965 BY FOCUSING ON IDENTIFYING THE 6106 03:54:37,965 --> 03:54:41,836 MOST RELEVANT AND PREDICTED 6107 03:54:41,836 --> 03:54:45,473 FEATURES. 6108 03:54:45,473 --> 03:54:46,974 SO SIMILAR TO DR. HOLDER, I 6109 03:54:46,974 --> 03:54:47,875 THINK THERE ARE SEVERAL 6110 03:54:47,875 --> 03:54:49,443 DIFFERENT APPLICATIONS OF 6111 03:54:49,443 --> 03:54:52,413 AUGMENTED INTELLIGENCE IN 6112 03:54:52,413 --> 03:54:53,280 SEPSIS. 6113 03:54:53,280 --> 03:54:54,382 PROBABLY THE MOST COMMON IS IN 6114 03:54:54,382 --> 03:54:55,850 DIAGNOSIS OR PREDICTION AS HE 6115 03:54:55,850 --> 03:54:57,485 WAS JUST COVERING, BUT I ALSO 6116 03:54:57,485 --> 03:54:58,686 THINK THERE ARE ASPECTS OF 6117 03:54:58,686 --> 03:54:59,754 APPLICATIONS IN TREATMENT 6118 03:54:59,754 --> 03:55:01,789 DECISION CHOICES AS WELL AS IN 6119 03:55:01,789 --> 03:55:06,494 PROGNOSIS. 6120 03:55:06,494 --> 03:55:07,928 SO AGAIN BECAUSE SEPSIS OFTEN 6121 03:55:07,928 --> 03:55:09,230 PRESENTS WITH VERY VAGUE SIGNS 6122 03:55:09,230 --> 03:55:10,798 AND SYMPTOMS AND THERE'S 6123 03:55:10,798 --> 03:55:11,899 SIGNIFICANT MORBIDITY ASSOCIATED 6124 03:55:11,899 --> 03:55:15,603 WITH EVEN HOURS OF DELAYED 6125 03:55:15,603 --> 03:55:20,274 DIAGNOSIS, MUCH OF THE RESEARCH 6126 03:55:20,274 --> 03:55:24,779 FOR A.I. IN SEPSIS HAS FOCUSED 6127 03:55:24,779 --> 03:55:26,847 ON IMPROVING PREDICTION AND 6128 03:55:26,847 --> 03:55:27,948 EARLY DIAGNOSIS. 6129 03:55:27,948 --> 03:55:29,717 THERE WERE 130 DIFFERENT SEPSIS 6130 03:55:29,717 --> 03:55:31,318 PREDICTED MODELS EXTRACTED AND 6131 03:55:31,318 --> 03:55:33,020 FOR THE PREDICTION OF SEPSIS 6132 03:55:33,020 --> 03:55:34,488 DIAGNOSTIC TEST ACCURACY 6133 03:55:34,488 --> 03:55:37,658 ASSESSED BY THE AUC RANGED FROM 6134 03:55:37,658 --> 03:55:41,028 ANYWHERE FROM .7 TO NEARLY 1. 6135 03:55:41,028 --> 03:55:44,699 SO WE HAVE MANY A VERY ACCURATE 6136 03:55:44,699 --> 03:55:45,032 MODEL. 6137 03:55:45,032 --> 03:55:46,667 JUST AS DR. HOLDER WAS 6138 03:55:46,667 --> 03:55:48,502 MENTIONING, A LOT OF THE EMR 6139 03:55:48,502 --> 03:55:50,438 DATA NOW IS NOT STRUCTURE DATA 6140 03:55:50,438 --> 03:55:51,205 ELEMENTS. 6141 03:55:51,205 --> 03:55:56,110 ONE STUDY FOUND 80% OF CLINICAL 6142 03:55:56,110 --> 03:55:59,346 DATA NOW IS -- THAT'S DATA 6143 03:55:59,346 --> 03:56:01,749 CAPTURED IN CLINICAL NOTES AND 6144 03:56:01,749 --> 03:56:02,216 IMAGES, FOR EXAMPLE. 6145 03:56:02,216 --> 03:56:03,217 THERE HAVE BEEN A COUPLE OF 6146 03:56:03,217 --> 03:56:04,318 STUDIES WITHIN THE LAST FEW 6147 03:56:04,318 --> 03:56:06,187 YEARS COMMENTING ON ADDITION OF 6148 03:56:06,187 --> 03:56:07,888 UNSTRUCTURED DATA IN PREDICTED 6149 03:56:07,888 --> 03:56:09,924 MODELS HAVING ADDED ACCURACY. 6150 03:56:09,924 --> 03:56:11,225 SO YOU CAN IMAGINE A FUTURE 6151 03:56:11,225 --> 03:56:12,960 HAVING MODELS THAT INCORPORATE 6152 03:56:12,960 --> 03:56:14,929 BOTH STRUCTURED DATA ELEMENTS AS 6153 03:56:14,929 --> 03:56:16,263 WELL AS UNSTRUCTURED DATA 6154 03:56:16,263 --> 03:56:18,499 ELEMENTS THAT HAVE A NEARLY 100% 6155 03:56:18,499 --> 03:56:24,505 ACCURACY IN PREDICTING SEPSIS. 6156 03:56:24,505 --> 03:56:26,540 SO THIS WAS A SCOPING REVIEW 6157 03:56:26,540 --> 03:56:27,641 INCLUDING 29 STUDIES OF MACHINE 6158 03:56:27,641 --> 03:56:30,778 LEARNING MODELS FOR SEPSIS 6159 03:56:30,778 --> 03:56:32,113 DETECTION ACROSS DIVERSE 6160 03:56:32,113 --> 03:56:33,881 CLINICAL SETTINGS, HAD OVER 6161 03:56:33,881 --> 03:56:34,815 1 MILLION PATIENT ENCOUNTERS AND 6162 03:56:34,815 --> 03:56:37,618 IT LOOKED AT THE DEDYNAMIC 6163 03:56:37,618 --> 03:56:38,552 VARIABLES INCLUDED IN THE MODEL. 6164 03:56:38,552 --> 03:56:40,521 AS YOU CAN SEE THE TOP FIVE WERE 6165 03:56:40,521 --> 03:56:42,490 ALL VITAL SIEB TRAM TERES. 6166 03:56:42,490 --> 03:56:43,858 THESE ARE THE VITAL SIGNS 6167 03:56:43,858 --> 03:56:45,593 COMMONLY MEASURED IN A 6168 03:56:45,593 --> 03:56:46,594 CONTINUOUS FASHION FOR MANY 6169 03:56:46,594 --> 03:56:47,795 PATIENTS IN THE HOSPITAL. 6170 03:56:47,795 --> 03:56:50,998 SO AGAIN AS I MENTIONED 6171 03:56:50,998 --> 03:56:52,333 PREVIOUSLY, WE HAVE THE 6172 03:56:52,333 --> 03:56:58,773 OPPORTUNITY TO CONTINUOUSLY 6173 03:56:58,773 --> 03:57:05,713 EVALUATE THESE DYNAMIC VAISH 6174 03:57:05,713 --> 03:57:06,580 VARIABLES. 6175 03:57:06,580 --> 03:57:08,649 I LOVE THE FACT THAT DR. HOLDER 6176 03:57:08,649 --> 03:57:11,051 ALSO CAPTURED THE IMPORTANCE OF 6177 03:57:11,051 --> 03:57:12,887 THE WINDOW OF PREDICTION. 6178 03:57:12,887 --> 03:57:15,656 SO THIS IS CRITICALLY IMPORTANT 6179 03:57:15,656 --> 03:57:17,591 PARTICULARLY FOR SEPSIS IN TERMS 6180 03:57:17,591 --> 03:57:19,460 OF CLINICAL INTERVENTION, WEE 6181 03:57:19,460 --> 03:57:22,329 SOURCE ALLOCATION, AS WELL AS 6182 03:57:22,329 --> 03:57:23,230 PLANNING FOR TREATMENT. 6183 03:57:23,230 --> 03:57:25,299 SO THIS FIGURE SHOWS THE IMPACT 6184 03:57:25,299 --> 03:57:30,838 OF DIFFERENT PREDICTIVE TIME 6185 03:57:30,838 --> 03:57:32,339 MODELS -- ON THE X AXIS YOU HAVE 6186 03:57:32,339 --> 03:57:34,542 TIME WINDOW TO SEPSIS AND THE 6187 03:57:34,542 --> 03:57:35,442 AUC ON THE Y AXIS. 6188 03:57:35,442 --> 03:57:37,678 YOU CAN SEE THAT ALL OF THEM 6189 03:57:37,678 --> 03:57:38,879 OVERALL PERFORMED VERY WELL 6190 03:57:38,879 --> 03:57:41,215 ACROSS THE ENTIRE SPECTRUM OF 6191 03:57:41,215 --> 03:57:42,116 PREDICTION, BUT FROM A CLINICIAN 6192 03:57:42,116 --> 03:57:46,787 PEPERSPECTIVE, WHAT WE'RE REALLY 6193 03:57:46,787 --> 03:57:50,357 HONING IN ON IS BETWEEN THE 6194 03:57:50,357 --> 03:57:51,759 1 AND 6 HOUR WINDOW. 6195 03:57:51,759 --> 03:57:54,628 AND MANY MODELS WITHIN THIS TIME 6196 03:57:54,628 --> 03:57:56,297 WINDOW WITH SIGNIFICANT ACCURACY 6197 03:57:56,297 --> 03:57:57,398 IN TERMS OF PREDICTING SEPSIS. 6198 03:57:57,398 --> 03:57:59,400 SO WITHIN THE POTENTIAL 6199 03:57:59,400 --> 03:58:01,235 APPLICATION OF A.I. FOR SEPSIS 6200 03:58:01,235 --> 03:58:02,469 DIAGNOSIS, I ALSO THINK IT'S 6201 03:58:02,469 --> 03:58:03,470 IMPORTANT TO THINK ABOUT THE 6202 03:58:03,470 --> 03:58:07,508 POTENTIAL FOR A.I. MODELS TO -- 6203 03:58:07,508 --> 03:58:09,877 SUBTYPES OF SEPSIS, SO THIS 6204 03:58:09,877 --> 03:58:12,279 PHENOMENAL PAPER BY DR. SEYMOUR 6205 03:58:12,279 --> 03:58:15,549 PUBLISHED IN 2019, HE DID A 6206 03:58:15,549 --> 03:58:17,585 RETROSPECTIVE ANALYSIS OF 6207 03:58:17,585 --> 03:58:18,919 DATASETS FROM PATIENTS WITH 6208 03:58:18,919 --> 03:58:21,088 SEPSIS AND IDENTIFIED FOUR NOVEL 6209 03:58:21,088 --> 03:58:21,755 SEPSIS PHENOTYPES. 6210 03:58:21,755 --> 03:58:23,390 I THINK THIS WAS SHOWN IN ONE OF 6211 03:58:23,390 --> 03:58:25,526 THE FINAL TALKS EARLIER TODAY, 6212 03:58:25,526 --> 03:58:27,494 THE A ALPHA, BETA, GAMMA AND 6213 03:58:27,494 --> 03:58:28,529 DELTA. 6214 03:58:28,529 --> 03:58:29,463 THE FOUR PHENOTYPES WERE 6215 03:58:29,463 --> 03:58:30,865 STRONGLY CORRELATED WITH OUTCOME 6216 03:58:30,865 --> 03:58:34,335 AND SIMULATION OF THREE -- 6217 03:58:34,335 --> 03:58:36,904 ESTIMATED TREAT FMENT WAS ALSO 6218 03:58:36,904 --> 03:58:38,439 SENSITIVE TO THE PHENOTYPE 6219 03:58:38,439 --> 03:58:39,306 DISTRIBUTION. 6220 03:58:39,306 --> 03:58:42,743 THIS SUGGESTS -- GROUPING 6221 03:58:42,743 --> 03:58:43,777 PATIENTS INTO DIFFERENT 6222 03:58:43,777 --> 03:58:44,345 PHENOTYPES. 6223 03:58:44,345 --> 03:58:45,579 IT MIGHT BE ABLE TO IDENTIFY 6224 03:58:45,579 --> 03:58:47,548 PATIENTS WHO WOULD BENEFIT FROM 6225 03:58:47,548 --> 03:58:50,417 SPECIFIC TREATMENT. 6226 03:58:50,417 --> 03:58:52,052 SO IN ADDITION TO GROUPING 6227 03:58:52,052 --> 03:58:53,520 PATIENTS INTO CERTAIN PHENOTYPES 6228 03:58:53,520 --> 03:58:55,055 WITH POTENTIALLY DIFFERENT 6229 03:58:55,055 --> 03:58:56,924 RESPONSES TO TREATMENT, A.I.'S 6230 03:58:56,924 --> 03:58:59,093 TOOLS HAVE ALSO BEEN USED TO 6231 03:58:59,093 --> 03:59:01,362 IDENTIFIED POSITIVE PATHOGENS 6232 03:59:01,362 --> 03:59:03,864 WHICH ALLOWED FOR TAILORED 6233 03:59:03,864 --> 03:59:05,532 TREATMENT FOR SEPSIS PATIENTS 6234 03:59:05,532 --> 03:59:08,068 WITH ANTIBIOTIC THERAPIES. 6235 03:59:08,068 --> 03:59:13,641 OR THE INFECTED ORGANISM. 6236 03:59:13,641 --> 03:59:15,376 SO GIVEN THE ABILITY TO ANALYZE 6237 03:59:15,376 --> 03:59:16,977 THESE HUGE DATASETS, A.I. HAS 6238 03:59:16,977 --> 03:59:18,846 THE CAPABILITY TO LOOK AT HOW 6239 03:59:18,846 --> 03:59:20,147 DIFFERENT PATIENT STRATEGIES MAY 6240 03:59:20,147 --> 03:59:21,749 IMPACT PATIENT OUTCOMES. 6241 03:59:21,749 --> 03:59:23,384 SO MODELS EVALUATING TREATMENT 6242 03:59:23,384 --> 03:59:25,352 STRATEGIES HAVE NOT YET BEEN 6243 03:59:25,352 --> 03:59:25,953 COMPREHENSIVELY VALIDATED BUT 6244 03:59:25,953 --> 03:59:28,589 THIS IS REALLY AN EXCITING AREA 6245 03:59:28,589 --> 03:59:29,890 OF OPPORTUNITY FOR A.I. AND 6246 03:59:29,890 --> 03:59:34,695 SEPSIS. 6247 03:59:34,695 --> 03:59:35,963 SO IN ADDITION TO ASSISTING 6248 03:59:35,963 --> 03:59:37,364 CLINICIANS WITH DIAGNOSIS AND 6249 03:59:37,364 --> 03:59:38,032 TREATMENT DECISIONS, TOOLS CAN 6250 03:59:38,032 --> 03:59:40,935 ALSO BE USED TO PREDICT PATIENT 6251 03:59:40,935 --> 03:59:42,069 OUTCOMES AND DR. HOLDER TOUCHED 6252 03:59:42,069 --> 03:59:42,670 ON THIS AS WELL. 6253 03:59:42,670 --> 03:59:43,771 THIS IS REALLY IMPORTANT WHEN 6254 03:59:43,771 --> 03:59:46,373 YOU THINK ABOUT SYSTEM-WIDE 6255 03:59:46,373 --> 03:59:47,875 RESOURCE ALLOCATION, SO BY 6256 03:59:47,875 --> 03:59:48,776 PREDICTING WHICH PATIENTS ARE 6257 03:59:48,776 --> 03:59:50,411 MORE LIKELY TO HAVE HIGHER 6258 03:59:50,411 --> 03:59:51,578 MORBIDITY OR MORTALITY, 6259 03:59:51,578 --> 03:59:54,882 HEALTHCARE SYSTEMS CAN USE THE 6260 03:59:54,882 --> 03:59:56,884 MODEL -- NURSE STAFFING RATIOS, 6261 03:59:56,884 --> 03:59:59,420 CLINICIAN WORKFLOWS, AND ALSO 6262 03:59:59,420 --> 04:00:00,187 FOCUS CLINICIAN ATTENTION WHERE 6263 04:00:00,187 --> 04:00:05,559 IT'S NEEDED MOST. 6264 04:00:05,559 --> 04:00:08,796 SO IF THESE A.I. MODELS WORK AND 6265 04:00:08,796 --> 04:00:09,797 THEY'RE ACCURATE IN TERMS OF 6266 04:00:09,797 --> 04:00:11,198 PREDICTION, WHY HAVE SO FEW BEEN 6267 04:00:11,198 --> 04:00:12,299 IMPLEMENTED IN CLINICAL 6268 04:00:12,299 --> 04:00:12,566 PRACTICE? 6269 04:00:12,566 --> 04:00:14,868 AND I APPRECIATE DR. HOLDER HIGH 6270 04:00:14,868 --> 04:00:15,836 LIEGHT THE SEVERAL THAT HAVE 6271 04:00:15,836 --> 04:00:16,603 BEEN IMPLEMENTED. 6272 04:00:16,603 --> 04:00:17,871 AND SOME OF THE CHALLENGES 6273 04:00:17,871 --> 04:00:24,011 ASSOCIATED WITH THAT. 6274 04:00:24,011 --> 04:00:26,180 A.I. MODELS RELY ON HIGH QUALITY 6275 04:00:26,180 --> 04:00:27,648 COMPREHENSIVE DATASETS TO 6276 04:00:27,648 --> 04:00:29,316 FUNCTION EFFECTIVELY. 6277 04:00:29,316 --> 04:00:30,617 HOWEVER, HEALTHCARE DATA IS 6278 04:00:30,617 --> 04:00:32,920 OFTEN FRAGMENTED ACROSS VARIOUS 6279 04:00:32,920 --> 04:00:35,923 SYSTEMS, THEY THERE ARE OFTEN 6280 04:00:35,923 --> 04:00:37,257 INCONSISTENCIES IN THE EHR, 6281 04:00:37,257 --> 04:00:38,659 THERE'S A LOT OF MISSING OR 6282 04:00:38,659 --> 04:00:39,893 INACCURATE DATA, WHICH ALL CAN 6283 04:00:39,893 --> 04:00:44,064 LEAD TO POOR MODEL PERFORMANCE. 6284 04:00:44,064 --> 04:00:46,233 ALSO MANY -- SINGLE INSTITUTION 6285 04:00:46,233 --> 04:00:47,401 OR A POPULATION OF PATIENTS AS 6286 04:00:47,401 --> 04:00:49,470 HE MENTIONED, WHICH MAKES IT 6287 04:00:49,470 --> 04:00:50,804 DIFFICULT TO GENERALIZE TO OTHER 6288 04:00:50,804 --> 04:00:51,572 SETTINGS. 6289 04:00:51,572 --> 04:00:54,475 A MODEL DEVELOPED USING DATA 6290 04:00:54,475 --> 04:00:55,676 FROM ONE HOSPITAL MAY NOT 6291 04:00:55,676 --> 04:00:57,111 PERFORM AS WELL DUE TO 6292 04:00:57,111 --> 04:00:59,113 VARIATIONS IN PATIENT 6293 04:00:59,113 --> 04:01:00,114 DEMOGRAPHICS, CLINICAL PRACTICE 6294 04:01:00,114 --> 04:01:05,352 AND DATA COLLECTION METHODS. 6295 04:01:05,352 --> 04:01:08,689 IN ADDITION, AS MENTIONED 6296 04:01:08,689 --> 04:01:10,891 PREVIOUSLY, SEPSIS HAS VAGUE 6297 04:01:10,891 --> 04:01:12,326 SYMPTOMS THAT OVERLAP WITH LESS 6298 04:01:12,326 --> 04:01:13,727 SEVERE FORMS OF INFECTION AND 6299 04:01:13,727 --> 04:01:15,329 WITH MANY NON-INFECTIOUS 6300 04:01:15,329 --> 04:01:15,996 DISEASES. 6301 04:01:15,996 --> 04:01:17,831 CLINICAL PRESENTATIONS CAN VARY 6302 04:01:17,831 --> 04:01:19,800 FROM PATIENT TO PATIENT SO THESE 6303 04:01:19,800 --> 04:01:24,505 FACTORS MAKE SEPSIS A DIFFICULT 6304 04:01:24,505 --> 04:01:25,572 DOAD, ADDITIONALLY YOU DON'T 6305 04:01:25,572 --> 04:01:30,277 HAVE THE BENEFIT OF TIME TO 6306 04:01:30,277 --> 04:01:31,111 OBTAIN -- BECAUSE EFFECTIVE 6307 04:01:31,111 --> 04:01:32,513 TREATMENT HAS TO BE INITIATED 6308 04:01:32,513 --> 04:01:33,947 WITHIN THE FIRST FEW HOURS OF 6309 04:01:33,947 --> 04:01:34,381 PRESENTATION. 6310 04:01:34,381 --> 04:01:36,750 SO THIS LEADS TO A PROBLEM 6311 04:01:36,750 --> 04:01:39,920 THAT'S INHERENT IN MANY -- FOR 6312 04:01:39,920 --> 04:01:41,655 THE MODEL TO BE ACCURATE, 6313 04:01:41,655 --> 04:01:43,023 OFTENTIMES IT INCORPORATES 6314 04:01:43,023 --> 04:01:43,824 DECISIONS THAT CLINICIANS HAVE 6315 04:01:43,824 --> 04:01:45,225 ALREADY MADE THAT INDICATE THAT 6316 04:01:45,225 --> 04:01:47,528 THEY SUSPECT IT'S SEPSIS, AND AT 6317 04:01:47,528 --> 04:01:49,430 THAT POINT, OBVIOUSLY THE OUTPUT 6318 04:01:49,430 --> 04:01:53,167 IS RELEVANT. 6319 04:01:53,167 --> 04:01:54,368 SO I THINK THIS IS THE 6320 04:01:54,368 --> 04:01:56,437 PARTICULAR ISSUE THAT WAS 6321 04:01:56,437 --> 04:01:58,839 HIGHLIGHTED IN THE STUDY ON THE 6322 04:01:58,839 --> 04:02:00,507 EPIC EHR MODEL DONE BY 6323 04:02:00,507 --> 04:02:01,175 UNIVERSITY OF MICHIGAN. 6324 04:02:01,175 --> 04:02:02,643 I THINK THIS REALLY HIGHLIGHTED 6325 04:02:02,643 --> 04:02:04,378 ONE OF THE MAIN ISSUES WITH 6326 04:02:04,378 --> 04:02:06,447 SEPSIS PREDICTIVE MODELS. 6327 04:02:06,447 --> 04:02:10,017 SO THIS STUDY LOOKED AT THE EPIC 6328 04:02:10,017 --> 04:02:10,651 EHR MODEL. 6329 04:02:10,651 --> 04:02:12,519 EPIC IS NOW SERVING OVER 50% OF 6330 04:02:12,519 --> 04:02:15,689 THE POPULATION IN THE U.S., 2.5% 6331 04:02:15,689 --> 04:02:16,890 OF PATIENTS INTERNATIONALLY, SO 6332 04:02:16,890 --> 04:02:19,359 IT'S A WIDELY USED EHR, AND IN 6333 04:02:19,359 --> 04:02:23,730 THIS STUDY, THEY LOOKED AT 6334 04:02:23,730 --> 04:02:26,633 77,000 ADULT PATIENTS 6335 04:02:26,633 --> 04:02:28,836 HOSPITALIZED IN -- OF THOSE 6336 04:02:28,836 --> 04:02:30,237 PATIENTS 5% WERE ULTIMATELY 6337 04:02:30,237 --> 04:02:31,605 DIAGNOSED AS HAVING SEPSIS AND 6338 04:02:31,605 --> 04:02:34,675 WHILE THE MODEL ACCURATELY 6339 04:02:34,675 --> 04:02:41,815 PREDICTED THE PATIENTS HAVING 6340 04:02:41,815 --> 04:02:43,083 SEPSIS 87% OF THE TIME, IT ONLY 6341 04:02:43,083 --> 04:02:44,852 DID SO 53% OF THE TIME BEFORE 6342 04:02:44,852 --> 04:02:46,887 PATIENTS HAD A BLOOD CULTURE 6343 04:02:46,887 --> 04:02:47,588 ORDER, SO ONLY ABOUT HALF THE 6344 04:02:47,588 --> 04:02:49,356 TIME DID IT PREDICT IT PRIOR TO 6345 04:02:49,356 --> 04:02:54,628 A CLINICIAN'S SUSPICION. 6346 04:02:54,628 --> 04:02:55,829 THE MODEL WHILE ACCURATE SEEMS 6347 04:02:55,829 --> 04:02:58,632 TO BE CUING IN ON DIAGNOSTIC 6348 04:02:58,632 --> 04:03:00,267 TESTS OR TREATMENTS THAT MADE 6349 04:03:00,267 --> 04:03:01,902 PREDICTIONS USELESS TO 6350 04:03:01,902 --> 04:03:02,769 CLINICIANS AT THIS POINT. 6351 04:03:02,769 --> 04:03:05,606 SO AGAIN THIS HIGHLIGHTS THE 6352 04:03:05,606 --> 04:03:07,441 MODEL IS INTEGRATED INTO THE 6353 04:03:07,441 --> 04:03:08,709 CLINICAL WORKFLOW AND IT 6354 04:03:08,709 --> 04:03:09,576 SOMETHING THAT SHOULD BE 6355 04:03:09,576 --> 04:03:13,981 EVALUATED WITH ANY NEW MODEL. 6356 04:03:13,981 --> 04:03:15,616 SO IN TERMS OF INCORPORATING IT, 6357 04:03:15,616 --> 04:03:16,683 IT'S CRITICALLY IMPORTANT THAT 6358 04:03:16,683 --> 04:03:20,354 THE IMPLEMENTATION BE SEAMLESS. 6359 04:03:20,354 --> 04:03:25,692 A.I. SYSTEMS HAVE TO BE EASY TO 6360 04:03:25,692 --> 04:03:28,395 USE, SEAMLESSLY INTEGRATED, AND 6361 04:03:28,395 --> 04:03:30,430 FOR SEPSIS, GIVEN THE PA RIDDITY 6362 04:03:30,430 --> 04:03:32,633 WITH WHICH IT MUST BE IDENTIFIED 6363 04:03:32,633 --> 04:03:34,735 AND TREATED, IT'S PARTICULARLY 6364 04:03:34,735 --> 04:03:36,503 CHALLENGING. 6365 04:03:36,503 --> 04:03:37,638 TRADITIONALLY, THERE IS THE 6366 04:03:37,638 --> 04:03:42,809 ISSUE OF ALARM FA TEAL. 6367 04:03:42,809 --> 04:03:44,778 AND THIS CAN CONTRIBUTE TO ALERT 6368 04:03:44,778 --> 04:03:46,413 FATIGUE, REDUCING YOUR 6369 04:03:46,413 --> 04:03:47,881 LIKELIHOOD OF THE SYSTEM BEING 6370 04:03:47,881 --> 04:03:50,751 TRUSTED AND USE. 6371 04:03:50,751 --> 04:03:52,286 IN ADDITION FALSE POSITIVES 6372 04:03:52,286 --> 04:03:53,820 ACTED UPON CAN HAVE IMPACT TO 6373 04:03:53,820 --> 04:03:56,156 THE PATIENT IN TERMS OF 6374 04:03:56,156 --> 04:03:58,692 UNNECESSARY ANTILIGHT IK 6375 04:03:58,692 --> 04:04:00,227 PRESCRIPTION, UNNECESSARILY DAIG 6376 04:04:00,227 --> 04:04:01,395 GNOSTIC TESTING. 6377 04:04:01,395 --> 04:04:04,198 SO AGAIN HIGHLIGHTED BY 6378 04:04:04,198 --> 04:04:05,199 DR. HOLDER ARE BARRIERS IN TERMS 6379 04:04:05,199 --> 04:04:05,632 OF TRUST. 6380 04:04:05,632 --> 04:04:08,435 SO THERE ARE SEVERAL FACTORS 6381 04:04:08,435 --> 04:04:09,970 THAT HELP WITH TRUST OF A.I. 6382 04:04:09,970 --> 04:04:10,504 MODELS. 6383 04:04:10,504 --> 04:04:11,939 FIRST OF ALL IS THE ACCURACY OF 6384 04:04:11,939 --> 04:04:13,540 THE MODEL ITSELF. 6385 04:04:13,540 --> 04:04:16,376 SO UNFORTUNATELY A.I. MODELS FOR 6386 04:04:16,376 --> 04:04:18,979 SEPSIS OFTEN LACK RIGOROUS LARGE 6387 04:04:18,979 --> 04:04:21,281 SCALE VALIDATION IN A DIVERSE 6388 04:04:21,281 --> 04:04:21,848 SETTING. 6389 04:04:21,848 --> 04:04:23,016 AND CLINICIANS WANT TO HAVE 6390 04:04:23,016 --> 04:04:24,418 EVIDENCE THAT THE A.I. TOOL 6391 04:04:24,418 --> 04:04:27,154 THAT'S IN USE IS HIGHLY ACCURATE 6392 04:04:27,154 --> 04:04:28,755 AND RELIABLE IN DIAGNOSING OR 6393 04:04:28,755 --> 04:04:30,324 PREDICTING CONDITIONS 6394 04:04:30,324 --> 04:04:31,158 PARTICULARLY FOR A CONDITION 6395 04:04:31,158 --> 04:04:33,126 SUCH AS SEPSIS WITH HIGH 6396 04:04:33,126 --> 04:04:36,930 MORBIDITY AND MORTALITY. 6397 04:04:36,930 --> 04:04:38,031 MANY A.I. MODELS PARTICULARLY 6398 04:04:38,031 --> 04:04:39,433 THOSE USING DEEP LEARNING ACT AS 6399 04:04:39,433 --> 04:04:41,268 BLACK BOXES, MAKING IT DIFFICULT 6400 04:04:41,268 --> 04:04:42,569 TO UNDERSTAND HOW PREDICTIONS 6401 04:04:42,569 --> 04:04:42,836 ARE MADE. 6402 04:04:42,836 --> 04:04:44,571 SO HAVING MODELS THAT ARE TRANTS 6403 04:04:44,571 --> 04:04:46,707 PARENT AND EXPLAINABLE ALSO 6404 04:04:46,707 --> 04:04:47,140 HELPS WITH TRUST. 6405 04:04:47,140 --> 04:04:49,009 AND THEN THERE ARE A NUMBER OF 6406 04:04:49,009 --> 04:04:50,477 HUMAN FACTORS THAT INFLUENCE 6407 04:04:50,477 --> 04:04:51,478 TRUST IN A.I. TOOLS. 6408 04:04:51,478 --> 04:04:53,113 SO CLINICIANS WHO HAVE MORE 6409 04:04:53,113 --> 04:04:54,314 EXPERIENCE ACTUALLY TEND TO BE 6410 04:04:54,314 --> 04:04:55,849 LESS TRUSTING OF A.I. SYSTEMS 6411 04:04:55,849 --> 04:04:57,251 DUE TO THE CONFIDENCE IN THEIR 6412 04:04:57,251 --> 04:04:58,986 OWN CLINICAL DECISION-MAKING, 6413 04:04:58,986 --> 04:05:00,320 WHEREAS JUNIOR CLINICIANS TEND 6414 04:05:00,320 --> 04:05:02,089 TO BE MORE OPEN TO TRUSTING A.I. 6415 04:05:02,089 --> 04:05:06,693 AS A SUPPORT TOOL. 6416 04:05:06,693 --> 04:05:10,197 STUDIES ALSO SHOW CLINICIANS ARE 6417 04:05:10,197 --> 04:05:11,565 LIKELY TO TRUST A.I. SYSTEMS 6418 04:05:11,565 --> 04:05:13,100 THAT ALIGN WITH THEIR OWN 6419 04:05:13,100 --> 04:05:14,201 EXPERTISE. 6420 04:05:14,201 --> 04:05:15,936 AND CLINICIANS WHO ARE JUST MORE 6421 04:05:15,936 --> 04:05:16,670 COMFORTABLE WITH DIGITAL TOOLS 6422 04:05:16,670 --> 04:05:18,438 AND A.I. IN GENERAL ARE LIKELY 6423 04:05:18,438 --> 04:05:22,976 TO HAVE HIGHER TRUST IN THESE 6424 04:05:22,976 --> 04:05:23,577 SYSTEMS. 6425 04:05:23,577 --> 04:05:28,348 AND CONTEXTUAL FACTORS FOR 6426 04:05:28,348 --> 04:05:29,549 TRUST, ALSO HAS TO DO WITH PEER 6427 04:05:29,549 --> 04:05:31,585 EB DORSMENT, SO CLINICIANS TEND 6428 04:05:31,585 --> 04:05:34,221 TO TRUST RECOMMENDATIONS FROM 6429 04:05:34,221 --> 04:05:35,088 THEIR COLLEAGUES, AND THIS CAN 6430 04:05:35,088 --> 04:05:37,024 HAVE A SIGNIFICANT IMPACT ON 6431 04:05:37,024 --> 04:05:37,991 PERCEIVED TRUSTWORTHINESS OF A 6432 04:05:37,991 --> 04:05:39,092 GIVEN A.I. TOOL. 6433 04:05:39,092 --> 04:05:40,694 LASTLY CLINICIANS AWARENESS OF 6434 04:05:40,694 --> 04:05:44,298 POTENTIAL BIASES IN THE A.I. 6435 04:05:44,298 --> 04:05:45,632 ALGORITHM CAN LEAD TO DISTRUST 6436 04:05:45,632 --> 04:05:47,134 IF THEY PERCEIVE THE A.I. TOOL 6437 04:05:47,134 --> 04:05:49,002 MIGHT BE UNFAIRLY TREATING 6438 04:05:49,002 --> 04:05:50,304 CERTAIN PATIENT GROUPS, SO 6439 04:05:50,304 --> 04:05:51,071 TRANSPARENCY IS CRITICALLY 6440 04:05:51,071 --> 04:05:53,040 IMPORTANT IN TERMS OF EFFORTS TO 6441 04:05:53,040 --> 04:05:54,641 MITIGATE BIAS AND FAIRNESS IN 6442 04:05:54,641 --> 04:05:55,842 MODEL DEVELOPMENT. 6443 04:05:55,842 --> 04:05:57,044 IF SHOULD INCLUDE A ROBUST 6444 04:05:57,044 --> 04:05:58,378 SYSTEM OF GOVERNANCE WITHIN THE 6445 04:05:58,378 --> 04:06:06,953 HEALTH SYSTEM. 6446 04:06:06,953 --> 04:06:08,388 GIVEN THE AFOREMENTIONED 6447 04:06:08,388 --> 04:06:10,057 CHALLENGES, HOW DO YOU 6448 04:06:10,057 --> 04:06:11,024 EFFECTIVELY INTEGRATE AN A.I. 6449 04:06:11,024 --> 04:06:11,992 TOOL INTO THE BEDSIDE? 6450 04:06:11,992 --> 04:06:13,427 STEP ONE IS TO FIND A MODEL THAT 6451 04:06:13,427 --> 04:06:17,097 WORKS. 6452 04:06:17,097 --> 04:06:18,465 SO THIS IS WHAT WE DID AT DUKE 6453 04:06:18,465 --> 04:06:20,033 BACK IN 2015, WHICH IS WHY THE 6454 04:06:20,033 --> 04:06:24,638 DEFINITION TO BE HONEST IS -- WE 6455 04:06:24,638 --> 04:06:26,606 CHOSE THE DEFINITION ON THE LEFT 6456 04:06:26,606 --> 04:06:27,641 AS OUR ELECTRONIC DEFINITION AND 6457 04:06:27,641 --> 04:06:29,643 THEN WE CONDUCTED A 6458 04:06:29,643 --> 04:06:31,044 RETROSPECTIVE DATA ANALYSIS 6459 04:06:31,044 --> 04:06:32,779 INCLUDING MORE THAN 42,000 6460 04:06:32,779 --> 04:06:34,414 INPATIENT ENCOUNTERS, AND WE 6461 04:06:34,414 --> 04:06:37,584 DEVELOPED A MACHINE LEARNING 6462 04:06:37,584 --> 04:06:39,319 MODEL. 6463 04:06:39,319 --> 04:06:40,320 SIMILAR TO SOME OF THE DATA 6464 04:06:40,320 --> 04:06:42,255 YOU'VE SEEN ALREADY, OUR MODEL 6465 04:06:42,255 --> 04:06:47,361 LISTED THERE IS MGP-RNN BECAUSE 6466 04:06:47,361 --> 04:06:48,995 IT'S A RECURRENT NEURAL NETWORK 6467 04:06:48,995 --> 04:06:50,630 MODEL OUTPERFORMED TWO OTHER 6468 04:06:50,630 --> 04:06:51,732 MACHINE LEARNING MODELS AND THEN 6469 04:06:51,732 --> 04:06:53,567 SOME OF THE POINT-BASED SCORING 6470 04:06:53,567 --> 04:06:55,335 SYSTEMS PRE-EXISTING. 6471 04:06:55,335 --> 04:06:57,704 FOR THE PURPOSE PS OF 6472 04:06:57,704 --> 04:06:58,805 TRANSPARENCY AND I WILL BE 6473 04:06:58,805 --> 04:07:00,640 HONEST AND SAY THIS IS ACTUALLY 6474 04:07:00,640 --> 04:07:02,075 A BLACK BOX MODEL SO IT DOESN'T 6475 04:07:02,075 --> 04:07:03,410 HAVE FULL TRANSPARENCY, BUT WE 6476 04:07:03,410 --> 04:07:05,545 DEVELOPED A SYSTEM TO EDUCATE 6477 04:07:05,545 --> 04:07:08,382 PHYSICIANS ABOUT CONTENT USE TO 6478 04:07:08,382 --> 04:07:10,150 BUILD MODEL AS WELL AS HOW 6479 04:07:10,150 --> 04:07:11,852 EFFECTIVE AND ACCURATE IT WAS IN 6480 04:07:11,852 --> 04:07:15,589 DETERMINING THE OUTCOME. 6481 04:07:15,589 --> 04:07:18,291 SO THEN AS I WAS GETTING TO, THE 6482 04:07:18,291 --> 04:07:18,959 IMPLEMENTATION IS CRITICALLY 6483 04:07:18,959 --> 04:07:22,996 IMPORTANT. 6484 04:07:22,996 --> 04:07:24,531 I JUST WANT TO HIGHLIGHT HOW WE 6485 04:07:24,531 --> 04:07:25,432 CHOSE TO IMPLEMENT IT. 6486 04:07:25,432 --> 04:07:27,033 SO WE ACTUALLY IDENTIFIED A 6487 04:07:27,033 --> 04:07:28,769 SINGLE END USER FOR OUR MODEL 6488 04:07:28,769 --> 04:07:31,071 OUTPUT AND BUILT AN A.I. 6489 04:07:31,071 --> 04:07:32,005 INTERFACE FOR THAT END USER 6490 04:07:32,005 --> 04:07:34,641 WHICH IS SHOWN ON THE RIGHT. 6491 04:07:34,641 --> 04:07:36,276 WHICH WAS BUILT IMPORTANTLY WITH 6492 04:07:36,276 --> 04:07:38,211 FRONT LINE STAFF FEEDBACK. 6493 04:07:38,211 --> 04:07:40,080 THIS WAS THEN INTEGRATED PRETTY 6494 04:07:40,080 --> 04:07:43,917 SEAMLESSLY INTO THE WORKFLOW AT 6495 04:07:43,917 --> 04:07:44,885 DUKE HOSPITAL IN THE EMERGENCY 6496 04:07:44,885 --> 04:07:48,522 DEPARTMENT. 6497 04:07:48,522 --> 04:07:50,223 THEN WE DEVELOPED A METHODOLOGY 6498 04:07:50,223 --> 04:07:54,961 FOR MODELING PATIENT OUTCOMES. 6499 04:07:54,961 --> 04:07:56,263 I'M GOING FAST TO TRY TO GET TO 6500 04:07:56,263 --> 04:07:57,230 THE HIGHLIGHT AND THAT IS THIS. 6501 04:07:57,230 --> 04:07:58,632 SO IN TERMS OF OUR PATIENT 6502 04:07:58,632 --> 04:08:00,267 OUTCOMES, THESE ARE OUR PROCESS 6503 04:08:00,267 --> 04:08:00,534 MEASURES. 6504 04:08:00,534 --> 04:08:03,203 IN ORDER TO VALIDATE THIS, THIS 6505 04:08:03,203 --> 04:08:05,372 IS AGAIN OUR PROSPECTIVE 6506 04:08:05,372 --> 04:08:07,240 IMPLEMENTATION, WE DID A 6507 04:08:07,240 --> 04:08:07,808 PRE/POST ANALYSIS. 6508 04:08:07,808 --> 04:08:09,176 THE POPULATIONS INCLUDED ARE 6509 04:08:09,176 --> 04:08:12,012 THOSE THAT MET THE CDC ADULT -- 6510 04:08:12,012 --> 04:08:14,381 I FELT LIKE THIS WAS THE MOST 6511 04:08:14,381 --> 04:08:15,048 ROBUST ELECTRONIC DEFINITION OF 6512 04:08:15,048 --> 04:08:15,315 PATIENTS. 6513 04:08:15,315 --> 04:08:16,750 YOU CAN SEE THAT IN ALL ELEMENTS 6514 04:08:16,750 --> 04:08:19,085 OF THE BUNDLES OF CARE WE SHOWED 6515 04:08:19,085 --> 04:08:20,587 IMPROVE THE PRE AND POST 6516 04:08:20,587 --> 04:08:25,525 IMPLEMENTATION, AND NEXT SLIDE, 6517 04:08:25,525 --> 04:08:26,526 THIS IS THE BIG HIGHLIGHT. 6518 04:08:26,526 --> 04:08:29,095 THIS IS OUR MORTALITY RATIO, 6519 04:08:29,095 --> 04:08:31,164 EXPECTED MORTALITY SINCE 6520 04:08:31,164 --> 04:08:31,832 IMPLEMENTATION, WE'VE NOW BEEN 6521 04:08:31,832 --> 04:08:33,667 LIVE FOR THE LAST FIVE YEARS AND 6522 04:08:33,667 --> 04:08:34,634 WE'VE SEEN A SUBSTANTIAL 6523 04:08:34,634 --> 04:08:35,602 IMPROVEMENT IN PATIENT MORTALITY 6524 04:08:35,602 --> 04:08:42,976 IN THAT POPULATION OF PATIENTS. 6525 04:08:42,976 --> 04:08:44,277 SO THIS IS THE CONCLUSION. 6526 04:08:44,277 --> 04:08:45,579 I THINK THESE ARE THE CRITICAL 6527 04:08:45,579 --> 04:08:47,113 ELEMENTS FOR EFFECTIVE A.I. 6528 04:08:47,113 --> 04:08:49,850 INTEGRATION INTO SEPSIS BEDSIDE 6529 04:08:49,850 --> 04:08:54,087 CARE AND I NOT FOR THE INTERESTF 6530 04:08:54,087 --> 04:08:55,255 TIME I'LL CLOSE THERE AND SEE IF 6531 04:08:55,255 --> 04:08:59,593 WE HAVE TIME FOR QUESTIONS. 6532 04:08:59,593 --> 04:09:00,560 >> THANK YOU VERY MUCH, 6533 04:09:00,560 --> 04:09:00,994 DR. O'BRIEN. 6534 04:09:00,994 --> 04:09:08,401 WE HAVE TIME FOR QUESTIONS. 6535 04:09:08,401 --> 04:09:11,338 YOU IDENTIFIED TECHNOLOGY, HUMAN 6536 04:09:11,338 --> 04:09:13,406 AND CONTEXTUAL FACTORS AS THREE 6537 04:09:13,406 --> 04:09:14,608 MAIN BUCKETS OF AREAS WHERE 6538 04:09:14,608 --> 04:09:17,010 THERE'S POTENTIAL BARRIERS AND 6539 04:09:17,010 --> 04:09:19,079 GAPS THAT NEED TO BE OVERCOME. 6540 04:09:19,079 --> 04:09:21,715 IN THE WORK THAT YOU LED AROUND 6541 04:09:21,715 --> 04:09:24,651 SEPSIS WATCH INTEGRATION, WHAT 6542 04:09:24,651 --> 04:09:26,386 DID YOU FIND TO TAKE THE MOST 6543 04:09:26,386 --> 04:09:28,955 TIME, TO BE THE MOST DIFFICULT, 6544 04:09:28,955 --> 04:09:31,858 YOU KNOW, AGAIN, TECH, I THINK, 6545 04:09:31,858 --> 04:09:35,428 HUMAN AND CONTEXTUAL? 6546 04:09:35,428 --> 04:09:36,863 >> BY FAR AND AWAY HUMAN. 6547 04:09:36,863 --> 04:09:38,932 AND IT REMAINS -- DESPITE OUR 6548 04:09:38,932 --> 04:09:40,867 SUCCESS, IT CONTINUES TO BE KIND 6549 04:09:40,867 --> 04:09:42,602 OF THE ONGOING SOURCES OF 6550 04:09:42,602 --> 04:09:46,106 CHALLENGE FOR THIS MODEL. 6551 04:09:46,106 --> 04:09:48,174 WE DESIGNED OUR IMPLEMENTATION 6552 04:09:48,174 --> 04:09:50,243 WORKFLOW WITH FRONT LINE STAFF 6553 04:09:50,243 --> 04:09:50,677 FEEDBACK. 6554 04:09:50,677 --> 04:09:52,212 BUT I THINK OVERCOMING THOSE 6555 04:09:52,212 --> 04:09:54,848 TRUST BARRIERS, PARTICULARLY AT 6556 04:09:54,848 --> 04:09:57,751 THE PROVIDER LEVEL, AND HOWING 6557 04:09:57,751 --> 04:09:58,852 THIS WAS GOING TO IMPACT 6558 04:09:58,852 --> 04:10:02,255 PROVIDER LEVEL AUTONOMY, TRYING 6559 04:10:02,255 --> 04:10:03,690 TO SELL IT THAT THIS WASN'T A 6560 04:10:03,690 --> 04:10:05,992 TOOL TO REPLACE DECISION-MAKING 6561 04:10:05,992 --> 04:10:08,028 BUT TO AUGMENT DISSECTION MAKING 6562 04:10:08,028 --> 04:10:09,262 TO BE ANOTHER PIECE OF EVIDENCE 6563 04:10:09,262 --> 04:10:10,430 THAT THE CLINICIAN COULD 6564 04:10:10,430 --> 04:10:11,498 ULTIMATELY USE TO MAKE THEIR 6565 04:10:11,498 --> 04:10:12,399 DECISION ABOUT CARE FOR THE 6566 04:10:12,399 --> 04:10:13,700 PATIENT, BUT HOW THAT WAS 6567 04:10:13,700 --> 04:10:15,001 MESSAGED, THE WORKFLOW WE 6568 04:10:15,001 --> 04:10:17,704 ACTUALLY USED IS THROUGH AN I 6569 04:10:17,704 --> 04:10:21,675 KRMECULEVEL NERS. 6570 04:10:21,675 --> 04:10:23,510 A SINGLE NURSE MONITORS OUR 6571 04:10:23,510 --> 04:10:25,245 PREDICTIVE MODEL ON ANY GIVEN 6572 04:10:25,245 --> 04:10:26,780 DAY AND THAT NURSE IS 6573 04:10:26,780 --> 04:10:28,315 RESPONSIBLE FOR MONITORING THE 6574 04:10:28,315 --> 04:10:30,050 ENTIRE BHJ DEPARTMENT AND 6575 04:10:30,050 --> 04:10:32,786 COMMUNICATING VIA EPIC WITH THE 6576 04:10:32,786 --> 04:10:33,820 CARE TEAM FOR THE PATIENT. 6577 04:10:33,820 --> 04:10:35,522 SO A LOT OF THOUGHT AND FEEDBACK 6578 04:10:35,522 --> 04:10:36,723 WENT INTO HOW THAT COMMUNICATION 6579 04:10:36,723 --> 04:10:39,426 ACTUALLY IS WORDED, SO THAT THE 6580 04:10:39,426 --> 04:10:41,394 PROVIDER DOESN'T FEEL LIKE THEIR 6581 04:10:41,394 --> 04:10:42,295 TOES ARE BEING STEPPED OP IN 6582 04:10:42,295 --> 04:10:44,464 TERMS OF DECISION-MAKING BUT YET 6583 04:10:44,464 --> 04:10:46,967 THEY'RE ALERTED TO PATIENTS 6584 04:10:46,967 --> 04:10:48,268 BEING HIGH RISK, AND THEN OF 6585 04:10:48,268 --> 04:10:49,936 COURSE A KEY ASPECT OF THE MODEL 6586 04:10:49,936 --> 04:10:51,972 THAT WE BUILT IS NOT JUST 6587 04:10:51,972 --> 04:10:52,539 IDENTIFICATION, BUT 6588 04:10:52,539 --> 04:10:53,573 FOLLOW-THROUGH FOR THE PATIENT 6589 04:10:53,573 --> 04:10:55,041 IN TERMS OF THE BUNDLE OF CARE. 6590 04:10:55,041 --> 04:10:56,810 SO THERE HAD TO BE ONGOING 6591 04:10:56,810 --> 04:10:58,244 COMMUNICATION OR AVENUES OF 6592 04:10:58,244 --> 04:10:58,979 COMMUNICATION BETWEEN THE 6593 04:10:58,979 --> 04:10:59,846 EMERGENCY DEPARTMENT TEAM AND 6594 04:10:59,846 --> 04:11:02,382 THE NURSE WHO'S MONITORING OUR 6595 04:11:02,382 --> 04:11:04,084 PREDICTIVE MODEL, SO FIGURING 6596 04:11:04,084 --> 04:11:07,721 OUT HOW TO MAKE THAT SEAMLESS SO 6597 04:11:07,721 --> 04:11:08,922 IT WOULDN'T WORK ADDITIVE FOR 6598 04:11:08,922 --> 04:11:11,091 TEAM AND THE ED. 6599 04:11:11,091 --> 04:11:12,058 INCLUDING HAVING OUR NURSE GO 6600 04:11:12,058 --> 04:11:13,860 DOWN TO THE EMERGENCY DEPARTMENT 6601 04:11:13,860 --> 04:11:16,997 TO HELP WITH CARE DELIVERY IF 6602 04:11:16,997 --> 04:11:19,165 THAT WERE NECESSARY, BUT WE 6603 04:11:19,165 --> 04:11:20,133 CONTINUE TO ITERATE ON HOW TO 6604 04:11:20,133 --> 04:11:21,568 MAKE THAT WORK BENEFICIAL FOR 6605 04:11:21,568 --> 04:11:22,836 THE FRONTLINE TEAM TAKING CARE 6606 04:11:22,836 --> 04:11:24,404 OF THE PATIENT. 6607 04:11:24,404 --> 04:11:25,905 >> AND THAT GETS A LITTLE BIT 6608 04:11:25,905 --> 04:11:29,175 INTO THE QUESTION OF WHAT DOES 6609 04:11:29,175 --> 04:11:31,444 THAT STAFFING LOOK LIKE? 6610 04:11:31,444 --> 04:11:34,347 IS THAT LIKE A 24 HOURS 7 DAYS A 6611 04:11:34,347 --> 04:11:36,216 WEEK S IT A WEEKDAY, DAY TIME 6612 04:11:36,216 --> 04:11:36,416 HOURS? 6613 04:11:36,416 --> 04:11:37,951 HOW WOULD YOU CROSS THAT 6614 04:11:37,951 --> 04:11:38,351 BARRIER? 6615 04:11:38,351 --> 04:11:43,623 >> YEAH, SO WE ACTUALLY STAFF IT 6616 04:11:43,623 --> 04:11:45,058 24/7, AND INTERESTINGLY, IT'S 6617 04:11:45,058 --> 04:11:46,026 PAIRED WITH OTHER DUTIES. 6618 04:11:46,026 --> 04:11:47,961 SO THE NURSE WHO'S MONITORING 6619 04:11:47,961 --> 04:11:49,396 THIS PARTICULAR PREDICTIVE MODEL 6620 04:11:49,396 --> 04:11:51,131 ALSO HAS OTHER CLINICAL 6621 04:11:51,131 --> 04:11:52,766 RESPONSIBILITIES, AND SO AT THIS 6622 04:11:52,766 --> 04:11:55,935 POINT, NOW WE'RE LOOKING INTO 6623 04:11:55,935 --> 04:11:57,270 HAVING THAT PARTICULAR NURSE 6624 04:11:57,270 --> 04:11:58,972 ALSO REMOTELY MONITOR OUR TWO 6625 04:11:58,972 --> 04:11:59,973 COMMUNITY HOSPITALS THAT ARE NOW 6626 04:11:59,973 --> 04:12:01,608 ALSO LIVE WITH OUR PREDICTIVE 6627 04:12:01,608 --> 04:12:02,575 MODEL, AND SO WE'RE WORKING 6628 04:12:02,575 --> 04:12:04,210 THROUGH WHAT IS THE ADDED 6629 04:12:04,210 --> 04:12:05,512 WORKLOAD, BUT ACTUALLY WHEN WE 6630 04:12:05,512 --> 04:12:07,580 MEASURED IT, WE'VE HAD SEVERAL 6631 04:12:07,580 --> 04:12:09,349 SOCIAL SCIENTISTS FOLLOW OUR 6632 04:12:09,349 --> 04:12:12,185 NURSE AROUND, AND MEASURE A 6633 04:12:12,185 --> 04:12:13,153 TIMELINESS OF CARE AND TIME 6634 04:12:13,153 --> 04:12:15,655 REQUIRED FOR THE ACTUAL WORKFLOW 6635 04:12:15,655 --> 04:12:16,890 ASSOCIATED WITH SEPSIS WATCH, 6636 04:12:16,890 --> 04:12:18,725 AND ACTUALLY FOR EACH ADDITIONAL 6637 04:12:18,725 --> 04:12:20,593 PATIENT ENCOUNTER, IT ONLY TAKES 6638 04:12:20,593 --> 04:12:22,562 THE NURSE FIVE MINUTES TO REVIEW 6639 04:12:22,562 --> 04:12:23,930 THE PATIENT'S CHART, COMMUNICATE 6640 04:12:23,930 --> 04:12:26,466 WITH THE E.D., DOCUMENT IN THE 6641 04:12:26,466 --> 04:12:27,033 CHART. 6642 04:12:27,033 --> 04:12:28,535 FROM A WORKFLOW PERSPECTIVE 6643 04:12:28,535 --> 04:12:29,636 ACTUALLY, THEY'RE CAPABLE OF 6644 04:12:29,636 --> 04:12:31,504 DOING A LOT OF OTHER CLINICAL 6645 04:12:31,504 --> 04:12:33,239 TASKS AND AT THE SAME TIME, 6646 04:12:33,239 --> 04:12:34,841 MANAGING MULTIPLE PATIENTS WHO 6647 04:12:34,841 --> 04:12:36,076 ARE EITHER IDENTIFIED AS HIGH 6648 04:12:36,076 --> 04:12:37,711 RISK OR HAVING SEPSIS AND 6649 04:12:37,711 --> 04:12:39,112 FOLLOWING THROUGH THOSE THAT 6650 04:12:39,112 --> 04:12:40,447 HAVE BEEN IDENTIFIED AS HAVING 6651 04:12:40,447 --> 04:12:41,648 SEPSIS THROUGH THEIR BUNDLES OF 6652 04:12:41,648 --> 04:12:41,981 CARE. 6653 04:12:41,981 --> 04:12:45,218 SO ACTUALLY ADDING -- WE DID NOT 6654 04:12:45,218 --> 04:12:46,653 ADD ANY ADDITIONAL FTE WHEN WE 6655 04:12:46,653 --> 04:12:47,954 WERE ADDING IN THE COMMUNITY 6656 04:12:47,954 --> 04:12:50,490 HOSPITALS BECAUSE THE AMOUNT OF 6657 04:12:50,490 --> 04:12:51,991 INCREMENTAL TIME -- COMMUNITY 6658 04:12:51,991 --> 04:12:54,194 HOSPITALS ARE 300 BEDS AND 600 6659 04:12:54,194 --> 04:12:56,930 BEDS, AND IN TERMS OF THE 6660 04:12:56,930 --> 04:12:58,832 INCREMENTAL ADDITIONAL CASES, IT 6661 04:12:58,832 --> 04:13:01,735 WAS WITHIN THE WORKFLOW OF THE 6662 04:13:01,735 --> 04:13:05,672 EXISTING NURSE TO DO REMOTELY. 6663 04:13:05,672 --> 04:13:07,273 >> GREAT. 6664 04:13:07,273 --> 04:13:08,274 OKAY, IN THE INTEREST OF TIME 6665 04:13:08,274 --> 04:13:08,908 WE'LL KEEP MOVING. 6666 04:13:08,908 --> 04:13:09,943 WE'LL HAVE A CHANCE TO CIRCLE 6667 04:13:09,943 --> 04:13:10,577 BACK HERE. 6668 04:13:10,577 --> 04:13:13,413 THANKS, DR. O'BRIEN. 6669 04:13:13,413 --> 04:13:15,915 IT'S MY PLEASURE TO INTRODUCE 6670 04:13:15,915 --> 04:13:18,118 DR. PRATIK SINHA, WHO IS AT THE 6671 04:13:18,118 --> 04:13:19,452 WASHINGTON UNIVERSITY SCHOOL OF 6672 04:13:19,452 --> 04:13:21,387 MEDICINE TO SPEAK TO US ABOUT 6673 04:13:21,387 --> 04:13:23,790 TOWARDS PERSONALIZED CARE: A.I. 6674 04:13:23,790 --> 04:13:25,859 FOR UNPACKING SEPSIS 6675 04:13:25,859 --> 04:13:29,162 HETEROGENEITY. 6676 04:13:29,162 --> 04:13:30,096 GO FOR IT. 6677 04:13:30,096 --> 04:13:31,664 >> THANK YOU, VINNY AND THE 6678 04:13:31,664 --> 04:13:34,634 TEAM, FOR THE INVITATION. 6679 04:13:34,634 --> 04:13:37,804 THESE ARE MY DISCLOSURES. 6680 04:13:37,804 --> 04:13:39,072 NONE OF THEM ARE DIRECTLY 6681 04:13:39,072 --> 04:13:41,808 RELEVANT TO THIS TALK. 6682 04:13:41,808 --> 04:13:43,143 AN OVERVIEW OF MY TALK IS I'M 6683 04:13:43,143 --> 04:13:44,744 GOING TO FIRST START TALKING 6684 04:13:44,744 --> 04:13:45,979 ABOUT HETEROGENEITY IN SEPSIS 6685 04:13:45,979 --> 04:13:48,581 AND WHY IT'S A PROBLEM. 6686 04:13:48,581 --> 04:13:50,784 AND THEN VERY BRIEFLY TOUCH UPON 6687 04:13:50,784 --> 04:13:52,719 SOME OF THE APPROACHES TO 6688 04:13:52,719 --> 04:13:53,820 TACKLING HETEROGENEITY IN 6689 04:13:53,820 --> 04:13:54,721 SEPSIS, AND I HAVE TO SAY 6690 04:13:54,721 --> 04:13:55,889 BECAUSE OF THE CONSTRAINT OF 6691 04:13:55,889 --> 04:13:57,757 TIME, ANOTHER DISCLOSURE IS THAT 6692 04:13:57,757 --> 04:14:00,059 I'M MOSTLY FOCUSED ON SEPSIS 6693 04:14:00,059 --> 04:14:02,028 PHENOTYPING FROM OUR LAB, PARTLY 6694 04:14:02,028 --> 04:14:03,730 BECAUSE I THINK IT'S ONE OF THE 6695 04:14:03,730 --> 04:14:06,933 CLOSEST THAT'S COMING TO THE 6696 04:14:06,933 --> 04:14:08,568 POINT OF INTERFACING WITH 6697 04:14:08,568 --> 04:14:11,504 CLINICAL TRIALS AND CLINICAL 6698 04:14:11,504 --> 04:14:12,605 IMPLEMENTATION, AND TO SHOW HOW 6699 04:14:12,605 --> 04:14:15,542 WE HAVE USED CLINICAL 6700 04:14:15,542 --> 04:14:16,309 IMPLEMENTATION, WE'VE USED 6701 04:14:16,309 --> 04:14:21,481 MACHINE LEARNING APPROACHES TO 6702 04:14:21,481 --> 04:14:22,649 GET AT THE CLINICAL 6703 04:14:22,649 --> 04:14:24,184 IMPLEMENTATION OF THESE SEPSIS 6704 04:14:24,184 --> 04:14:24,517 PHENOTYPES. 6705 04:14:24,517 --> 04:14:25,819 ALSO TO REMEMBER THAT I MIGHT 6706 04:14:25,819 --> 04:14:26,820 NOT EMPHASIZE THIS BUT 6707 04:14:26,820 --> 04:14:27,587 THROUGHOUT MOST OF THE DATA I'M 6708 04:14:27,587 --> 04:14:28,788 GOING TO SHOW YOU FROM OUR LAB, 6709 04:14:28,788 --> 04:14:31,491 WE HAVE LEVERAGED DEEPLY MACHINE 6710 04:14:31,491 --> 04:14:32,826 LEARNING ALGORITHMS TO TRY AND 6711 04:14:32,826 --> 04:14:34,360 IDENTIFY PHENOTYPES AND THE 6712 04:14:34,360 --> 04:14:37,730 CLINICAL IMPLEMENTATION. 6713 04:14:37,730 --> 04:14:38,898 SO A GOOD PLACE TO START THIS 6714 04:14:38,898 --> 04:14:39,799 TALK WOULD BE TO ASK THE 6715 04:14:39,799 --> 04:14:41,768 QUESTION WHAT IS SEPSIS. 6716 04:14:41,768 --> 04:14:45,271 ACCORDING TO THE BIOLOGICAL 6717 04:14:45,271 --> 04:14:46,239 DEFINITION IN THE SEPSIS 3 KRAI 6718 04:14:46,239 --> 04:14:52,412 T3 CRITERIA, SEPSIS IS DESCRIBED 6719 04:14:52,412 --> 04:14:53,780 AS A LIFE-THREATENING ORGAN 6720 04:14:53,780 --> 04:14:55,081 DYSFUNCTION CAUSED BY A 6721 04:14:55,081 --> 04:14:56,382 DYSREGULATED HOST RESPONSE TO 6722 04:14:56,382 --> 04:14:56,649 INFECTION. 6723 04:14:56,649 --> 04:14:57,717 ALL THE TEXT YOU SEE IN COLORED 6724 04:14:57,717 --> 04:15:02,956 FONT ARE REALLY THE TRIUBERATE 6725 04:15:02,956 --> 04:15:05,191 THAT BIOLOGICALLY DESCRIBE 6726 04:15:05,191 --> 04:15:06,259 SEPSIS BUT EVEN A MOMENTARY 6727 04:15:06,259 --> 04:15:08,027 PAUSE WILL LEAD US TO ALL AGREE 6728 04:15:08,027 --> 04:15:09,729 THAT ALL OF THESE STATEMENTS ARE 6729 04:15:09,729 --> 04:15:10,930 INCREDIBLY NEBULOUS AND TO A 6730 04:15:10,930 --> 04:15:12,799 LARGE EXTENT SUBJECTIVE. 6731 04:15:12,799 --> 04:15:14,434 SO UNSURPRISINGLY, IT CAPTURES A 6732 04:15:14,434 --> 04:15:19,339 WHOLE HOST OF -- A MYRIAD OF 6733 04:15:19,339 --> 04:15:21,107 BIOLOGICAL PATHOPHYSIOLOGIES, 6734 04:15:21,107 --> 04:15:27,447 ETIOLOGIES INTO THIS DEFINITION. 6735 04:15:27,447 --> 04:15:28,748 NOW WHILE WE'VE SPENT A LOT OF 6736 04:15:28,748 --> 04:15:30,216 TIME TRYING TO UNDERSTAND THE 6737 04:15:30,216 --> 04:15:31,384 MOLECULAR BASIS OF THE HOST 6738 04:15:31,384 --> 04:15:32,252 RESPONSE, WE'VE NOT MANAGED TO 6739 04:15:32,252 --> 04:15:32,685 PIN IT. 6740 04:15:32,685 --> 04:15:34,087 WHAT WE DO KNOW IS THAT IT'S 6741 04:15:34,087 --> 04:15:37,957 HIGHLY COMPLEK, COMPLEX AND ALST 6742 04:15:37,957 --> 04:15:39,492 IT'S HIGHLY TIME VARIANT AND 6743 04:15:39,492 --> 04:15:40,026 DYNAMIC. 6744 04:15:40,026 --> 04:15:43,196 SO WE'VE TAKEN ALL THIS 6745 04:15:43,196 --> 04:15:43,863 INCREDIBLE 50 YEARS OF 6746 04:15:43,863 --> 04:15:45,064 BIOLOGICAL INFORMATION WE'VE 6747 04:15:45,064 --> 04:15:46,466 GATHERED ABOUT PATHOGENS, THE 6748 04:15:46,466 --> 04:15:48,001 HOST RESPONSE, AND THIS IS 6749 04:15:48,001 --> 04:15:52,605 CURRENTLY HOW WE DEFINE SEPSIS. 6750 04:15:52,605 --> 04:15:55,108 THIS LIFE-THREATENING ORGAN 6751 04:15:55,108 --> 04:15:56,643 DYSFUNCTION OF DYSREGULATED HOST 6752 04:15:56,643 --> 04:15:57,610 RESPONSE TO INFECTION. 6753 04:15:57,610 --> 04:16:00,113 IF YOU HAVE A SUSPECTED 6754 04:16:00,113 --> 04:16:02,015 INFECTION, YOU HAVE A SOFA SCORE 6755 04:16:02,015 --> 04:16:03,950 OF 2 OR MORE, ACCORDING TO THE 6756 04:16:03,950 --> 04:16:07,186 SEPSIS 3 KRAI TIER 3 CRITERIA, E 6757 04:16:07,186 --> 04:16:08,121 SEPSIS. 6758 04:16:08,121 --> 04:16:08,888 UNSURPRISINGLY, WHEN WE LOOK AT 6759 04:16:08,888 --> 04:16:11,724 HOW THIS SLO SHOWS UP IN THE 6760 04:16:11,724 --> 04:16:14,694 CLINICAL SPECTRUM IN THIS HIGHLY 6761 04:16:14,694 --> 04:16:17,530 UNDERRATED PAPER, THIS IS A CORE 6762 04:16:17,530 --> 04:16:19,399 DIAGRAM THAT LOOKS AT THE 6763 04:16:19,399 --> 04:16:21,067 DOMINANT TREATMENT TOPICS ON 6764 04:16:21,067 --> 04:16:23,670 HOUSE PATIENTS THAT MEET THE 6765 04:16:23,670 --> 04:16:24,871 SEPSIS DEFINITION SHOW UP IN 6766 04:16:24,871 --> 04:16:25,204 EHR. 6767 04:16:25,204 --> 04:16:30,710 I'M GOING TO GIVE YOU A PITHY 6768 04:16:30,710 --> 04:16:32,178 SUMMARY OF THIS, BUT AS YOU CAN 6769 04:16:32,178 --> 04:16:33,680 SEE SEPSIS IS A HOT MESS AS WE 6770 04:16:33,680 --> 04:16:34,881 DEFINE IT CLINICALLY. 6771 04:16:34,881 --> 04:16:37,150 SO WHY IS THIS A PROBLEM? 6772 04:16:37,150 --> 04:16:41,454 WELL, ROGER BONE ASKED WHY DO 6773 04:16:41,454 --> 04:16:44,490 SEPSIS TRIALS FAIL AND SEPSIS IS 6774 04:16:44,490 --> 04:16:47,660 REFERRED TO AS THE GRAVEYARD FOR 6775 04:16:47,660 --> 04:16:48,661 PHARMACOTHERAPIES. 6776 04:16:48,661 --> 04:16:50,296 OVER 200 TRIALS, WE'VE FAILED TO 6777 04:16:50,296 --> 04:16:51,564 IDENTIFY ANY BIOLOGICAL 6778 04:16:51,564 --> 04:16:52,799 INTERVENTION THAT IMPROVES 6779 04:16:52,799 --> 04:16:53,066 OUTCOMES. 6780 04:16:53,066 --> 04:16:54,434 SO IT'S A PROBLEM, PARTICULARLY 6781 04:16:54,434 --> 04:16:59,038 WHEN YOU'RE TRYING TO ATTRACT 6782 04:16:59,038 --> 04:17:01,040 PHARMA TO TRY AND SUPPORT SEPSIS 6783 04:17:01,040 --> 04:17:05,378 RESEARCH. 6784 04:17:05,378 --> 04:17:06,813 SO THE QUESTION IS CAN WE DO 6785 04:17:06,813 --> 04:17:11,718 SEPSIS TRIALS BETTER? 6786 04:17:11,718 --> 04:17:13,152 SO ONE APPROACH IS ABOUT 6787 04:17:13,152 --> 04:17:14,821 PHENOTYPING, THE IDEA BEING YOU 6788 04:17:14,821 --> 04:17:16,089 TAKE A HETEROGENEOUS POPULATION 6789 04:17:16,089 --> 04:17:17,957 AND YOU IDENTIFY UNIQUE 6790 04:17:17,957 --> 04:17:20,360 DISCRIMINATING FEATURES TO 6791 04:17:20,360 --> 04:17:21,461 SUBGROUP PATIENTS INTO AND THEN 6792 04:17:21,461 --> 04:17:22,562 TEST OUT THERAPIES ON THAT. 6793 04:17:22,562 --> 04:17:24,230 BROADLY SPEAKING, THERE ARE TWO 6794 04:17:24,230 --> 04:17:24,964 ARMS TO THIS ONE. 6795 04:17:24,964 --> 04:17:26,366 THIS ONE IS PROGNOSTIC 6796 04:17:26,366 --> 04:17:26,699 ENRICHMENT. 6797 04:17:26,699 --> 04:17:28,468 HERE YOU IDENTIFY SUBGROUPS OF 6798 04:17:28,468 --> 04:17:29,702 PATIENTS WHERE THE OUTCOME OF 6799 04:17:29,702 --> 04:17:31,537 INTEREST, SAY FOR EXAMPLE, 6800 04:17:31,537 --> 04:17:33,606 MORTALITY, OR VASOOPPRESSOR USE 6801 04:17:33,606 --> 04:17:35,108 IS HIGHER AND YOU TEST YOUR 6802 04:17:35,108 --> 04:17:36,442 INTERVENTION IN THAT GROUP, BUT 6803 04:17:36,442 --> 04:17:38,411 THE HOLY GRAIL, REALLY, IS 6804 04:17:38,411 --> 04:17:40,213 PREDICTIVE ENRICHMENT, AND THIS 6805 04:17:40,213 --> 04:17:42,115 MEANS THAT YOU IDENTIFY 6806 04:17:42,115 --> 04:17:44,217 SUBGROUPS WITH UNIFORM BIOLOGY 6807 04:17:44,217 --> 04:17:46,586 AND THEN YOU IDENTIFY THERAPIES 6808 04:17:46,586 --> 04:17:48,421 TO MATCH THAT PATHOPHYSIOLOGICAL 6809 04:17:48,421 --> 04:17:49,956 FEATURE AND THIS IS DONE QUITE 6810 04:17:49,956 --> 04:17:51,190 FREQUENTLY IN CANCER BIOLOGY. 6811 04:17:51,190 --> 04:17:54,293 AND THIS IS THE DOMAIN THAT OUR 6812 04:17:54,293 --> 04:17:56,095 LAB AND OUR COLLABORATORS ARE 6813 04:17:56,095 --> 04:17:58,598 MOST INTERESTED IN. 6814 04:17:58,598 --> 04:18:04,404 SO THERE ARE -- I'M GOING TO 6815 04:18:04,404 --> 04:18:09,242 SORT OF PASS AN ODOR NOW TO THEE 6816 04:18:09,242 --> 04:18:10,543 FACT THAT SEPSIS IS A COMPLEX 6817 04:18:10,543 --> 04:18:11,944 SYSTEM BIOLOGY PROBLEM. 6818 04:18:11,944 --> 04:18:14,113 IN MY BIASED OPINION, THE WAY WE 6819 04:18:14,113 --> 04:18:15,915 CAN IDENTIFY ROBUST SUBGROUPS IS 6820 04:18:15,915 --> 04:18:18,284 THROUGH USING MULTIVARIATE 6821 04:18:18,284 --> 04:18:19,385 MODELING, AND POTENTIALLY WHEN 6822 04:18:19,385 --> 04:18:21,754 WE EVENTUALLY GET THERE, 6823 04:18:21,754 --> 04:18:24,290 MULTIDIMENSIONAL MODELING. 6824 04:18:24,290 --> 04:18:26,492 SO IT IS HARDLY SURPRISING THAT 6825 04:18:26,492 --> 04:18:28,694 THE LARGEST GAINS BEING MADE IN 6826 04:18:28,694 --> 04:18:32,065 THIS FIELD OF SEPSIS PHENOTYPING 6827 04:18:32,065 --> 04:18:34,901 IS TO TAKE THIS NEBULOUS 6828 04:18:34,901 --> 04:18:37,870 SYNDROME, AND TRY AND FIND 6829 04:18:37,870 --> 04:18:40,373 UNDERLYING DISEASE STATES, 6830 04:18:40,373 --> 04:18:42,775 BECAUSE BIOLOGICAL THERAPIES ARE 6831 04:18:42,775 --> 04:18:44,110 ONLY -- PROBABLY ONLY LIKELY FOR 6832 04:18:44,110 --> 04:18:44,577 DISEASE STATES. 6833 04:18:44,577 --> 04:18:45,845 IN FACT, MACHINE LEARNING 6834 04:18:45,845 --> 04:18:46,913 MODELS, WHEN YOU TRAIN THEM TO 6835 04:18:46,913 --> 04:18:48,247 DISEASE STATES, ARE MUCH MORE 6836 04:18:48,247 --> 04:18:50,016 LIKELY TO WORK BETTER THAN THEY 6837 04:18:50,016 --> 04:18:52,285 ARE IF YOU TAKE A NEBULOUS SOME 6838 04:18:52,285 --> 04:18:56,222 SYNDROME OR COLLECTION OF 6839 04:18:56,222 --> 04:18:58,257 SYMPTOMS. 6840 04:18:58,257 --> 04:18:59,725 SO THESE ARE SOME OF THE 6841 04:18:59,725 --> 04:19:01,360 MEASUREMENT SYSTEMS USED TO 6842 04:19:01,360 --> 04:19:04,197 IDENTIFY THE PHENOTYPES. 6843 04:19:04,197 --> 04:19:07,266 IN TERMS OF DNA, WE'RE STILL IN 6844 04:19:07,266 --> 04:19:08,134 ITS INFANCY. 6845 04:19:08,134 --> 04:19:10,203 ARGUABLY SOME OF THE BIGGEST 6846 04:19:10,203 --> 04:19:13,606 GAINS THAT HAVE BEEN MADE HAS 6847 04:19:13,606 --> 04:19:16,542 BEEN THROUGH TRANSCRIPTOMICS. 6848 04:19:16,542 --> 04:19:18,211 HECTOR WONG, WHO WAS A PIONEER 6849 04:19:18,211 --> 04:19:21,147 IN THIS FIELD 15 YEARS AGO IN 6850 04:19:21,147 --> 04:19:23,216 PEDIATRICS DESCRIBED SUBCLASS A 6851 04:19:23,216 --> 04:19:26,285 AND B BASED ON -- AND MORE 6852 04:19:26,285 --> 04:19:28,588 RECENTLY THERE HAVE BEEN THE SRS 6853 04:19:28,588 --> 04:19:32,625 AND THE MARS PHENOTYPES. 6854 04:19:32,625 --> 04:19:35,495 CHRIS SEYMOUR AND HIS GROUP HAVE 6855 04:19:35,495 --> 04:19:37,363 USED EHR-BASED DATA. 6856 04:19:37,363 --> 04:19:40,299 THE SENECA GROUPS BUT ALSO 6857 04:19:40,299 --> 04:19:45,638 TEMPERATURE TRAJECTORIES. 6858 04:19:45,638 --> 04:19:48,174 METABOLOMICS, POTENTIALLY 6859 04:19:48,174 --> 04:19:49,842 EXCITING MODE OF INVESTIGATION, 6860 04:19:49,842 --> 04:19:51,677 GIVES YOU QUITE A LOT OF DATA 6861 04:19:51,677 --> 04:19:53,279 BUT IT'S STILL IN ITS INFANCY. 6862 04:19:53,279 --> 04:19:54,680 THE BULK OF THIS TALK IS GOING 6863 04:19:54,680 --> 04:19:56,082 TO BE FOCUSED ON THE WORK THAT 6864 04:19:56,082 --> 04:19:58,050 WE'VE BEEN DOING, WHICH IS THE 6865 04:19:58,050 --> 04:19:59,886 HYPO AND HYPERINFLAMMATORY 6866 04:19:59,886 --> 04:20:01,854 PHENOTYPES BASED ON PROTEIN 6867 04:20:01,854 --> 04:20:02,955 SIGNATURES BUT THERE'S ALSO 6868 04:20:02,955 --> 04:20:07,660 GREAT WORK DONE IN THIS FIELD IN 6869 04:20:07,660 --> 04:20:11,264 THOSE THAT HAVE LOOKED AT 6870 04:20:11,264 --> 04:20:13,533 BIOMARKERS IN CIRCULATION TO TRY 6871 04:20:13,533 --> 04:20:14,767 AND DEFINE SUBGROUPS AND 6872 04:20:14,767 --> 04:20:15,067 PHENOTYPES. 6873 04:20:15,067 --> 04:20:16,569 AS YOU CAN SEE THESE ARE ALL 6874 04:20:16,569 --> 04:20:17,970 COMPLEX DATA, AND BECAUSE THESE 6875 04:20:17,970 --> 04:20:20,706 ARE MULTIVARIATE DATA THAT ARE 6876 04:20:20,706 --> 04:20:21,807 ASSOCIATED, SOMETIMES LINEAR, 6877 04:20:21,807 --> 04:20:22,775 SOMETIMES NON-LINEAR 6878 04:20:22,775 --> 04:20:24,844 ASSOCIATIONS WITH EACH OTHER. 6879 04:20:24,844 --> 04:20:25,945 THE USE OF ARTIFICIAL 6880 04:20:25,945 --> 04:20:26,712 INTELLIGENCE AND MACHINE 6881 04:20:26,712 --> 04:20:27,780 LEARNING HAS BEEN CRITICAL TO 6882 04:20:27,780 --> 04:20:30,550 TRY AND BETTER UNDERSTAND THIS 6883 04:20:30,550 --> 04:20:31,083 DATA. 6884 04:20:31,083 --> 04:20:33,286 AND I AM GLAD THAT THIS IS ON 6885 04:20:33,286 --> 04:20:34,620 ZOOM BECAUSE NO STATISTICIANS 6886 04:20:34,620 --> 04:20:37,423 CAN BEAT ME UP, BUT I DO WONDER 6887 04:20:37,423 --> 04:20:40,159 WHETHER SOMETIMES OUR RELIANCE 6888 04:20:40,159 --> 04:20:41,827 ON STUDYING THIS COMPLEX SYSTEMS 6889 04:20:41,827 --> 04:20:44,263 BIOLOGY PROBLEM WITH STANDARD 6890 04:20:44,263 --> 04:20:46,732 STATISTICAL LINEAR AND 6891 04:20:46,732 --> 04:20:49,135 LOGISTICAL REGRESSION MAY HAVE 6892 04:20:49,135 --> 04:20:51,237 UNDERMINED OUR EFFORTS TO 6893 04:20:51,237 --> 04:20:52,872 UNDERSTAND THESE COMPLEX 6894 04:20:52,872 --> 04:20:53,773 BIOLOGICAL INTERACTIONS. 6895 04:20:53,773 --> 04:20:54,941 SO MOVING ON TO THE WORK THAT WE 6896 04:20:54,941 --> 04:20:57,176 HAVE BEEN DOING, THIS WORK HAS 6897 04:20:57,176 --> 04:21:00,947 BEEN PIONEERED BY PROFESSOR AT 6898 04:21:00,947 --> 04:21:03,349 UCSF, AND HERE WHAT SHE DID WAS 6899 04:21:03,349 --> 04:21:04,784 USE UNBIASED APPROACHES TO 6900 04:21:04,784 --> 04:21:06,118 IDENTIFY SUBGROUPS USING 6901 04:21:06,118 --> 04:21:11,524 MULTIVARIATE SOLUTIONS, USING AN 6902 04:21:11,524 --> 04:21:13,426 APPROACH CALLED LATENT CLASS 6903 04:21:13,426 --> 04:21:15,761 ANALYSIS, A COMPOSITE OF 6904 04:21:15,761 --> 04:21:17,930 CLINICAL AND BIOLOGICAL DATA. 6905 04:21:17,930 --> 04:21:19,232 REALLY THE PREMISE OF 6906 04:21:19,232 --> 04:21:21,033 IDENTIFYING PHENOTYPES WITHIN A 6907 04:21:21,033 --> 04:21:22,335 SYNDROME OR A DISEASE IS THAT IT 6908 04:21:22,335 --> 04:21:26,038 SHOULD BE USEFUL, ROBUST, 6909 04:21:26,038 --> 04:21:27,506 REPRODUCIBLE, GENERALIZABLE AND 6910 04:21:27,506 --> 04:21:28,040 CLINICALLY IMPLEMENTABLE. 6911 04:21:28,040 --> 04:21:29,342 I HOPE TO SHOW YOU THAT WE HAVE 6912 04:21:29,342 --> 04:21:31,744 AT LEAST ATTAINED SOME OF THESE 6913 04:21:31,744 --> 04:21:38,217 OVER THE COURSE OF TIME. 6914 04:21:38,217 --> 04:21:40,186 SO WE'VE IDENTIFIED TWO 6915 04:21:40,186 --> 04:21:41,721 PHENOTYPES, IN THE RED IS THE 6916 04:21:41,721 --> 04:21:42,855 HYPERINFLAMMATORY, IN THE BLUE 6917 04:21:42,855 --> 04:21:44,390 IS THE HYPOINFLAMMATORY 6918 04:21:44,390 --> 04:21:45,224 PHENOTYPE. 6919 04:21:45,224 --> 04:21:48,394 ON THE X AXIS ARE THE CONTINUOUS 6920 04:21:48,394 --> 04:21:50,463 CLASS DEFINING VARIABLES AND THE 6921 04:21:50,463 --> 04:21:52,531 Y AXIS IS THE MEAN STANDARDIZED 6922 04:21:52,531 --> 04:21:53,532 DEFINING VARIABLES. 6923 04:21:53,532 --> 04:21:54,667 THE HYPERINFLAMMATORY PHENOTYPE 6924 04:21:54,667 --> 04:21:55,835 IS CALLED OUT BECAUSE IT'S 6925 04:21:55,835 --> 04:21:57,603 ASSOCIATED WITH HIGHER 6926 04:21:57,603 --> 04:21:59,338 PRO-INFLAMMATORY CYTOKINES, 6927 04:21:59,338 --> 04:22:01,107 LOWER BICARBONATES, LOWER BLOOD 6928 04:22:01,107 --> 04:22:02,208 PRESSURE AND INCREASED ORGAN 6929 04:22:02,208 --> 04:22:02,975 FAILURE. 6930 04:22:02,975 --> 04:22:05,911 ABOUT 30% OF THE POPULATION 6931 04:22:05,911 --> 04:22:12,518 ACROSS MULTI-BEL MULTIPLE COHOR. 6932 04:22:12,518 --> 04:22:14,787 MORTALITY INCLUDING PEDIATRIC -- 6933 04:22:14,787 --> 04:22:18,858 WHERE WE FOUND -- IN 6934 04:22:18,858 --> 04:22:21,060 CONSISTENTLY HIGHER IN THE 6935 04:22:21,060 --> 04:22:21,694 HYPERINFLAMMATORY PHENOTYPE 6936 04:22:21,694 --> 04:22:23,896 COMPARED TO THE 6937 04:22:23,896 --> 04:22:27,500 HYPERINFLAMMATORY PHENOTYPE. 6938 04:22:27,500 --> 04:22:34,607 WE'VE ALSO IN SECONDARY ANALYSIS 6939 04:22:34,607 --> 04:22:38,110 OF -- WE'VE HEARD DIFFERENTIAL 6940 04:22:38,110 --> 04:22:39,979 TREATMENT AND IN THE 6941 04:22:39,979 --> 04:22:42,915 SECONDARY -- OF HARP 2 WE SAW 6942 04:22:42,915 --> 04:22:46,752 SURVIVAL BENEFIT IN THE 6943 04:22:46,752 --> 04:22:47,553 HYPERINFLAMMATORY PHENOTYPE BUT 6944 04:22:47,553 --> 04:22:48,621 NOT IN THE HYPO. 6945 04:22:48,621 --> 04:22:50,056 IT'S IMPORTANT TO EMPHASIZE IN 6946 04:22:50,056 --> 04:22:52,391 ALL OF THESE THREE TRIALS BASED 6947 04:22:52,391 --> 04:22:59,031 ON CO CONVENTIONAL METRICS OF A, 6948 04:22:59,031 --> 04:23:00,433 SUGGESTING THESE PHENOTYPES 6949 04:23:00,433 --> 04:23:02,868 IDENTIFY FEATURES THAT MAY BE 6950 04:23:02,868 --> 04:23:04,403 AMENABLE TO DIFFERENTIAL 6951 04:23:04,403 --> 04:23:09,241 TREATMENT RESPONSES. 6952 04:23:09,241 --> 04:23:10,543 SO WHERE MY SORT OF RESEARCH 6953 04:23:10,543 --> 04:23:11,277 PROGRAM HAS BEEN LEADING IS TO 6954 04:23:11,277 --> 04:23:13,512 ASK THE QUESTION, CAN WE EXPAND 6955 04:23:13,512 --> 04:23:18,217 THESE PHENOTYPES INTO SEPSIS? 6956 04:23:18,217 --> 04:23:20,052 AGAIN USING LATENT CLASS 6957 04:23:20,052 --> 04:23:21,487 ANALYSIS IN EARLY WHICH IS AN 6958 04:23:21,487 --> 04:23:22,722 OBSERVATIONAL COHORT OF 6959 04:23:22,722 --> 04:23:25,224 CRITICALLY ILL PATIENTS IN -- 6960 04:23:25,224 --> 04:23:27,526 WITH SEPTIC SHOCK, WE OBSERVED 6961 04:23:27,526 --> 04:23:29,395 THE SAME TWO PHENOTYPES WITH THE 6962 04:23:29,395 --> 04:23:30,529 SAME TWO FEATURES. 6963 04:23:30,529 --> 04:23:32,798 WE TOOK A PARSIMONIOUS MODEL, I 6964 04:23:32,798 --> 04:23:33,999 WILL SPEAK OF IT A LITTLE BIT 6965 04:23:33,999 --> 04:23:35,634 MORE, WHICH WE TRAINED, WE 6966 04:23:35,634 --> 04:23:37,636 REDUCED THESE LCA MODELS OF 30 6967 04:23:37,636 --> 04:23:39,138 TO 40 VARIABLES DOWN TO THREE OR 6968 04:23:39,138 --> 04:23:42,341 FOUR VARIABLES, TO PREDICT THESE 6969 04:23:42,341 --> 04:23:43,342 FINE PHOENIX TYPES, SO THESE 6970 04:23:43,342 --> 04:23:49,482 PHENOTYPES, WE POINTED TO 6971 04:23:49,482 --> 04:23:51,083 PREDICT THESE SEPSIS PHENOTYPES 6972 04:23:51,083 --> 04:23:53,652 AND THEN WE REPEATED THIS IN 6973 04:23:53,652 --> 04:23:55,488 ANOTHER 1100 PATIENTS SO IN TWO 6974 04:23:55,488 --> 04:23:58,457 INDEPENDENT COHORTS TOTALING 6975 04:23:58,457 --> 04:24:00,659 2,000 PATIENTS, THE SAME TWO 6976 04:24:00,659 --> 04:24:01,761 PHENOTYPES WERE IDENTIFIED IN 6977 04:24:01,761 --> 04:24:02,495 PATIENTS, CRITICALLY ILL 6978 04:24:02,495 --> 04:24:04,363 PATIENTS WITH SEPSIS. 6979 04:24:04,363 --> 04:24:05,898 ANOTHER INTERESTING FEATURE THAT 6980 04:24:05,898 --> 04:24:07,566 WE WERE ABLE TO DO THROUGH THE 6981 04:24:07,566 --> 04:24:10,069 SEPSIS ANALYSIS WAS THAT 30% OF 6982 04:24:10,069 --> 04:24:11,837 THE PATIENTS WITH THE 6983 04:24:11,837 --> 04:24:12,938 HYPERINFLAMMATORY PHENOTYPE HAVE 6984 04:24:12,938 --> 04:24:18,210 POSITIVE BLOOD CULTURES, AND NOT 6985 04:24:18,210 --> 04:24:19,278 ONLY THAT THERE WAS A 6986 04:24:19,278 --> 04:24:21,180 PREDOMINENCE OF GRAM-NEGATIVE 6987 04:24:21,180 --> 04:24:22,348 SEPTICEMIA IN THE 6988 04:24:22,348 --> 04:24:23,015 HYPERINFLAMMATORY PHENOTYPE BUT 6989 04:24:23,015 --> 04:24:25,885 NOT THE HYPOINFLAMMATORY 6990 04:24:25,885 --> 04:24:26,318 PHENOTYPE. 6991 04:24:26,318 --> 04:24:28,521 THIS WAS CONSISTENT ACROSS FOUR 6992 04:24:28,521 --> 04:24:29,588 DIFFERENT COHORT WHICH I DON'T 6993 04:24:29,588 --> 04:24:30,689 HAVE TIME TO SHOW YOU, BUT 6994 04:24:30,689 --> 04:24:32,124 YOU'LL HAVE TO BELIEVE ME, 6995 04:24:32,124 --> 04:24:33,526 AROUND 30% IS CONSISTENT. 6996 04:24:33,526 --> 04:24:37,463 WE THEN USED AGAIN SON MACHINE 6997 04:24:37,463 --> 04:24:40,566 LEARNING APPROACHES WITH META 6998 04:24:40,566 --> 04:24:42,568 GENOMICS SEQUENCING SO WE LOOKED 6999 04:24:42,568 --> 04:24:44,170 AT THE DNA OF PATHOGENS AND 7000 04:24:44,170 --> 04:24:45,805 CIRCULATION AND FOUND THAT 7001 04:24:45,805 --> 04:24:47,573 PATHOGEN DOMINANCE WAS SIG 7002 04:24:47,573 --> 04:24:49,241 RANTLY HIGHER IN THE 7003 04:24:49,241 --> 04:24:50,676 HYPERINFLAMMATORY COMPARED TO 7004 04:24:50,676 --> 04:24:52,178 THE HYPOINFLAMMATORY PHENOTYPE 7005 04:24:52,178 --> 04:24:53,512 AND THIS SLIDE IS NOT SHOWN 7006 04:24:53,512 --> 04:24:55,481 PROPERLY BUT I ASSURE YOU THAT 7007 04:24:55,481 --> 04:24:59,752 THERE WAS, AGAIN, A PREDOMINENCE 7008 04:24:59,752 --> 04:25:06,459 OF THE -- ACCORDING TO META 7009 04:25:06,459 --> 04:25:09,395 GENOMICS FROM BLOOD OF PATIENTS 7010 04:25:09,395 --> 04:25:14,867 WITH SEPSIS THAT THE 7011 04:25:14,867 --> 04:25:16,402 HYPERINFLAMMATORY PHENOTYPE 7012 04:25:16,402 --> 04:25:20,573 STRONGLY ASSOCIATED WITH IT. 7013 04:25:20,573 --> 04:25:22,441 FINALLY AND MOST RECENTLY IN THE 7014 04:25:22,441 --> 04:25:24,844 SECONDARY ANALYSIS OF THE 7015 04:25:24,844 --> 04:25:27,713 CLOVERS TRIAL WHICH IS A SEPTIC 7016 04:25:27,713 --> 04:25:30,316 SHOCK TRIAL OF FLUIDS, WE AGAIN 7017 04:25:30,316 --> 04:25:32,151 OBSERVED THE SAME TWO 7018 04:25:32,151 --> 04:25:33,953 PHENOTYPES, AND I WILL TAKE YOUR 7019 04:25:33,953 --> 04:25:38,457 ATTENTION TO THE FACT THAT ONLY 7020 04:25:38,457 --> 04:25:40,960 3% PATIENTS HAD ARDS, AND 7021 04:25:40,960 --> 04:25:43,496 BECAUSE THIS CLOVERS COHORT WAS 7022 04:25:43,496 --> 04:25:46,165 IN THE PLJ DEPART EMERGENCY DEPD 7023 04:25:46,165 --> 04:25:47,867 IT WAS EARLY, 50% OF THESE 7024 04:25:47,867 --> 04:25:49,869 PATIENTS HAD POSITIVE 7025 04:25:49,869 --> 04:25:50,536 BACTEREMIA, SUGGESTING THAT BACT 7026 04:25:50,536 --> 04:25:52,705 RBACTEREMIA IS AN IMPORTANT 7027 04:25:52,705 --> 04:25:54,039 FEATURE THAT EXPLAINS THE 7028 04:25:54,039 --> 04:25:55,174 VARIANCE OF THE 7029 04:25:55,174 --> 04:25:57,977 HYPERINFLAMMATORY PHENOTYPE. 7030 04:25:57,977 --> 04:25:59,612 SO A BIG ROADBLOCK IS THAT HOW 7031 04:25:59,612 --> 04:26:02,348 DO YOU TAKE THESE COMPLEX MODELS 7032 04:26:02,348 --> 04:26:03,816 AND IMPLEMENT THEM TO THE 7033 04:26:03,816 --> 04:26:04,149 BEDSIDE? 7034 04:26:04,149 --> 04:26:06,385 HOW DO WE TAKE THESE 30, 40 7035 04:26:06,385 --> 04:26:07,386 MULTIVARIATE SOLUTIONS AND BRING 7036 04:26:07,386 --> 04:26:09,154 THEM TO THE BEDSIDE SO THAT WE 7037 04:26:09,154 --> 04:26:11,023 CAN DO CLINICAL TRIALS AND TEST 7038 04:26:11,023 --> 04:26:11,957 THERAPIES? 7039 04:26:11,957 --> 04:26:13,225 WE'VE TAKEN TWO APPROACHES. 7040 04:26:13,225 --> 04:26:15,327 ONE IS TO TAKE THESE 30 OR 40 7041 04:26:15,327 --> 04:26:16,395 VARIABLES AND REDUCE THEM TO 7042 04:26:16,395 --> 04:26:17,096 THREE OR FOUR. 7043 04:26:17,096 --> 04:26:19,331 I SHOWED YOU THE PARSIMONIOUS 7044 04:26:19,331 --> 04:26:19,532 MODEL. 7045 04:26:19,532 --> 04:26:21,267 AND THE SECOND, AND AGAIN, THIS 7046 04:26:21,267 --> 04:26:22,935 IS THE SORT OF RESEARCH THAT MY 7047 04:26:22,935 --> 04:26:25,471 GROUP HAS BEEN DOING, IS TO TAKE 7048 04:26:25,471 --> 04:26:28,440 PROTEIN BIOMARKERS SUCH AS 7049 04:26:28,440 --> 04:26:30,709 IL-6 -- WHICH WE DON'T HAVE 7050 04:26:30,709 --> 04:26:31,944 POINT OF CARE MEASURES FOR, TAKE 7051 04:26:31,944 --> 04:26:33,245 THAT OUT OF THE EQUATION AND 7052 04:26:33,245 --> 04:26:37,383 JUST USE CLINICAL DATA. 7053 04:26:37,383 --> 04:26:39,485 IN TERMS OF THE PARSIMONIOUS 7054 04:26:39,485 --> 04:26:40,486 MODEL IN THIS SMALL PROOF OF CON 7055 04:26:40,486 --> 04:26:44,757 ACCEPT CONCEPT STUDY WE DID, BOH 7056 04:26:44,757 --> 04:26:46,058 INVESTIGATORS IN THE U.K., WE 7057 04:26:46,058 --> 04:26:48,127 USED THE PARSIMONIOUS MODEL OF 7058 04:26:48,127 --> 04:26:51,630 IL-6, SOLUBLE TNFR-1 AND SODIUM 7059 04:26:51,630 --> 04:26:54,833 BICARBONATE IN 40 PATIENTS WITH 7060 04:26:54,833 --> 04:26:56,235 COVID-19, AND CLASSIFIED THEM IN 7061 04:26:56,235 --> 04:26:58,671 REALTIME IN LESS THAN TWO HOURS, 7062 04:26:58,671 --> 04:27:02,274 TO THE HYPER SC AND 7063 04:27:02,274 --> 04:27:04,443 HYPOINFLAMMATORY PHENOTYPE. 7064 04:27:04,443 --> 04:27:06,512 THIS WAS USING A NOVEL POINT OF 7065 04:27:06,512 --> 04:27:10,749 CARE DEVICE TO QAWPT FIGHT THESE 7066 04:27:10,749 --> 04:27:12,184 PROTEINS, THERE'S A LARGER STUDY 7067 04:27:12,184 --> 04:27:13,385 THAT JUST STOPPED RECRUITING AND 7068 04:27:13,385 --> 04:27:15,487 WE'RE HOPING TO GET DATA FROM 7069 04:27:15,487 --> 04:27:15,821 THIS SOON. 7070 04:27:15,821 --> 04:27:18,123 THIS IS A FINE STUDY WHICH USED 7071 04:27:18,123 --> 04:27:20,292 THIS POINT OF CARE DEVICE TO 7072 04:27:20,292 --> 04:27:21,827 CLASSIFY THE PATIENT INTO THE 7073 04:27:21,827 --> 04:27:24,363 HIGH POPE AND HYPERINFLAMMATORY 7074 04:27:24,363 --> 04:27:25,698 PHENOTYPE IN 550 PATIENTS. 7075 04:27:25,698 --> 04:27:26,765 THIS IS IMPORTANT BECAUSE IT 7076 04:27:26,765 --> 04:27:28,767 TAKES THE NEXT STEP TOWARDS A 7077 04:27:28,767 --> 04:27:34,673 CLINICAL TRIAL. 7078 04:27:34,673 --> 04:27:38,611 HOWEVER WHAT WE FOUND WAS NOT 7079 04:27:38,611 --> 04:27:40,145 IMMEDIATELY POSSIBLE WAS TO 7080 04:27:40,145 --> 04:27:42,881 MEASURE THESE PROTEIN MARKERS 7081 04:27:42,881 --> 04:27:46,852 UBIQUITOUSLY AT THE BEDSIDE, SO 7082 04:27:46,852 --> 04:27:48,821 THESE ARE STANDARD DATA 7083 04:27:48,821 --> 04:27:50,689 COLLECTED ACROSS MULTIPLE -- 7084 04:27:50,689 --> 04:27:55,527 ACROSS MOST I KRMECUs, THEY SAID 7085 04:27:55,527 --> 04:27:57,563 GOOD PERFORMANCE METRICS, AND WE 7086 04:27:57,563 --> 04:27:58,497 OBSERVED THAT THERE WAS 7087 04:27:58,497 --> 04:28:06,372 DIFFICULT RENGDIFFERENTIAL RESPH 7088 04:28:06,372 --> 04:28:09,441 BENEFIT IN THE -- AS YOU CAN 7089 04:28:09,441 --> 04:28:11,844 SEE, THIS MACHINE LEARNING MODEL 7090 04:28:11,844 --> 04:28:13,712 THAT ONLY USED CLINICAL DATA, 7091 04:28:13,712 --> 04:28:15,781 NOT ONLY HAVE HIGH PERFORMANCE 7092 04:28:15,781 --> 04:28:17,750 METRICS IN IDENTIFYING THE 7093 04:28:17,750 --> 04:28:20,085 COMPLEX LCA DERIVED PHENOTYPES, 7094 04:28:20,085 --> 04:28:21,820 BUT ALSO WAS ABLE TO CAPTURE THE 7095 04:28:21,820 --> 04:28:22,721 DIFFERENTIAL TREATMENT 7096 04:28:22,721 --> 04:28:23,455 RESPONSES. 7097 04:28:23,455 --> 04:28:26,325 SO WHAT WE DID WAS LOOKED AT 7098 04:28:26,325 --> 04:28:30,062 WHICH OF THESE FEATURES ARE MOST 7099 04:28:30,062 --> 04:28:30,829 PREDOMINANT AND THE MOST 7100 04:28:30,829 --> 04:28:37,302 IMPORTANT FEATURES WITHIN THE -- 7101 04:28:37,302 --> 04:28:38,537 MODEL, BUT FROM THE RED AND THE 7102 04:28:38,537 --> 04:28:39,938 ORANGE OR YELLOW AS YOU PROBABLY 7103 04:28:39,938 --> 04:28:41,940 SEE IT HERE, YOU CAN SEE THAT 7104 04:28:41,940 --> 04:28:43,909 THE PREDOMINANT FEATURES WERE 7105 04:28:43,909 --> 04:28:45,110 LABORATORY VALUES AND VITAL 7106 04:28:45,110 --> 04:28:45,511 SIGNS. 7107 04:28:45,511 --> 04:28:47,746 SO WHAT WE DID WAS WE TOOK OUT 7108 04:28:47,746 --> 04:28:49,081 ALL OF THE DEMOGRAPHIC 7109 04:28:49,081 --> 04:28:51,517 VARIABLES, WE TOOK OUT ALL OF 7110 04:28:51,517 --> 04:28:53,085 THE HESS PRIOR TRI -- AND 7111 04:28:53,085 --> 04:28:55,421 DEVELOPED A VITAL SIGNS AND 7112 04:28:55,421 --> 04:28:57,589 LABORATORY ONLY XG BOOST MODEL 7113 04:28:57,589 --> 04:29:00,325 TO PREDICT THESE PHENOTYPES. 7114 04:29:00,325 --> 04:29:10,869 THEN WE POINTED TO SEPSIS RCT -- 7115 04:29:13,005 --> 04:29:13,706 LARGE MULTICENTER TRIAL THAT 7116 04:29:13,706 --> 04:29:16,241 TESTED THE TREATMENT EFFICACY OF 7117 04:29:16,241 --> 04:29:19,278 ACTIVATED PROTEIN C VERSUS 7118 04:29:19,278 --> 04:29:20,479 PLACEBO AND THE ORIGINAL TRIAL 7119 04:29:20,479 --> 04:29:21,714 SHOWED NO BENEFIT, INCLUDING 7120 04:29:21,714 --> 04:29:27,186 WHEN THEY DID A ROBUST SUBGROUP 7121 04:29:27,186 --> 04:29:29,722 ANALYSIS WHICH INCLUDED APACHE 7122 04:29:29,722 --> 04:29:30,989 SCORES, SURFACE SCORES, PROTEIN 7123 04:29:30,989 --> 04:29:32,458 SEA LEVELS, BUT NONE OF THESE 7124 04:29:32,458 --> 04:29:34,860 WERE ABLE TO SHOW HETEROGENEITY 7125 04:29:34,860 --> 04:29:35,861 OF TREATMENT EFFECT. 7126 04:29:35,861 --> 04:29:38,731 SO WE TOOK THE CLINICAL 7127 04:29:38,731 --> 04:29:42,334 CLASSIFIED MODEL OF, I DON'T 7128 04:29:42,334 --> 04:29:44,636 HAVE TIME TO SHOW YOU THIS DATA, 7129 04:29:44,636 --> 04:29:47,806 BUT THE CLIL CAL FEATURES AND 7130 04:29:47,806 --> 04:29:49,341 OUTCOMES WERE CONSISTENT WITH 7131 04:29:49,341 --> 04:29:51,977 ALL OF OUR PREVIOUS DATA. 7132 04:29:51,977 --> 04:29:53,645 INTERESTINGLY, HOWEVER, WHAT WE 7133 04:29:53,645 --> 04:29:54,947 FOUND WAS THAT THERE WAS 7134 04:29:54,947 --> 04:29:56,348 SIGNIFICANT DIFFERENTIAL 7135 04:29:56,348 --> 04:30:00,419 TREATMENT RESPONSE IN THE HYPER 7136 04:30:00,419 --> 04:30:01,620 AND HYPOINFLAMMATORY PHENOTYPE. 7137 04:30:01,620 --> 04:30:05,791 ON THE X AXIS HERE IS A 7138 04:30:05,791 --> 04:30:07,893 PROBABILITY OF BELONGING TO THE 7139 04:30:07,893 --> 04:30:08,994 HYPERINFLAMMATORY PHENOTYPE, 7140 04:30:08,994 --> 04:30:11,296 WHILE ONE IS THAT YOU HAVE 100% 7141 04:30:11,296 --> 04:30:12,931 PROBABILITY OF HYPER AND ZERO IS 7142 04:30:12,931 --> 04:30:15,234 THAT YOU HAVE 100% PROBABILITY 7143 04:30:15,234 --> 04:30:16,769 OF THE HYPO. 7144 04:30:16,769 --> 04:30:18,871 THEN ON THE Y AXIS, IT'S THE 7145 04:30:18,871 --> 04:30:19,538 28-DAY MORTALITY. 7146 04:30:19,538 --> 04:30:24,209 AS YOU CAN SEE, AS YOUR 7147 04:30:24,209 --> 04:30:25,544 PROBABILITY OF BELONGING TO THE 7148 04:30:25,544 --> 04:30:26,979 HYPERAPPROACH IS ONE, IN GREEN 7149 04:30:26,979 --> 04:30:29,047 HERE IS ACTIVATED PROTEIN C. 7150 04:30:29,047 --> 04:30:30,949 THERE'S A SIGNIFICANT TREATMENT 7151 04:30:30,949 --> 04:30:32,684 BENEFIT WHEREAS IF YOU'RE THE 7152 04:30:32,684 --> 04:30:33,952 MORE HYPOYOU ARE, THE MORE 7153 04:30:33,952 --> 04:30:37,990 LIKELY YOU ARE TO BE HARMED BY 7154 04:30:37,990 --> 04:30:39,057 ACTIVATED PROTEIN SEE, SHOWING 7155 04:30:39,057 --> 04:30:42,060 AGAIN THAT OUR SIMPLISTIC 7156 04:30:42,060 --> 04:30:43,462 DEFINITIONS SUBSUMES SO MUCH 7157 04:30:43,462 --> 04:30:44,363 HETEROGENEITY IN PATIENT 7158 04:30:44,363 --> 04:30:47,065 POPULATION THAT THIS PHENOTYPING 7159 04:30:47,065 --> 04:30:49,501 SCHEMA MAY HAVE PERTINENT 7160 04:30:49,501 --> 04:30:50,269 TREATMENT IMPLICATIONS. 7161 04:30:50,269 --> 04:30:52,037 AGAIN I WILL EMPHASIZE WE'VE 7162 04:30:52,037 --> 04:30:53,338 DONE THIS JUST USING MACHINE 7163 04:30:53,338 --> 04:30:55,007 LEARNING MODELS THAT USE READILY 7164 04:30:55,007 --> 04:30:57,676 AVAILABLE CLINICAL DATA. 7165 04:30:57,676 --> 04:30:59,311 SO WE TOOK THE CLINICAL MODEL 7166 04:30:59,311 --> 04:31:02,714 AND POINTED THIS TIME TO THE 7167 04:31:02,714 --> 04:31:03,916 EUPHRATES TRIAL, A SLIGHTLY 7168 04:31:03,916 --> 04:31:05,417 SMALLER TRIAL OF ABOUT 4050 7169 04:31:05,417 --> 04:31:10,923 PATIENTS THAT TESTED POLYMYXIN 7170 04:31:10,923 --> 04:31:14,092 B, AGAIN I WILL EMPHASIZE THESE 7171 04:31:14,092 --> 04:31:15,527 WERE VERY SICK PATIENTS WITH 7172 04:31:15,527 --> 04:31:17,196 VERY HIGH ENDOTOXIN MODELS. 7173 04:31:17,196 --> 04:31:19,264 THERE WERE NO BENEFITS IN THE 7174 04:31:19,264 --> 04:31:22,968 ORIGINAL TRIAL. 7175 04:31:22,968 --> 04:31:25,404 HERE TOO, USING THIS CLINICAL 7176 04:31:25,404 --> 04:31:28,240 CLASSIFYING MODEL ON THE X AXIS 7177 04:31:28,240 --> 04:31:29,374 PROBABILITY BELONGING TO THE 7178 04:31:29,374 --> 04:31:31,443 HYPERINFLAMMATORY PHENOTYPE, 7179 04:31:31,443 --> 04:31:35,080 AGAIN DIFFERENTIAL TREATMENT 7180 04:31:35,080 --> 04:31:36,281 INTERACTION. 7181 04:31:36,281 --> 04:31:38,684 AGAIN, SIGNAL TO BENEFIT IN THE 7182 04:31:38,684 --> 04:31:40,485 HYPER AND THE MORE HYPERYOU GOT 7183 04:31:40,485 --> 04:31:42,020 SIGNAL TO HARM IN THE HYPO. 7184 04:31:42,020 --> 04:31:44,957 AND IT'S WORTH THINKING THAT IF 7185 04:31:44,957 --> 04:31:48,660 YOUR OVERALL MORTALITY IS 7186 04:31:48,660 --> 04:31:50,128 APPROACHING 10% AND YOU USE 7187 04:31:50,128 --> 04:31:50,996 THESE INTERVENTIONS THAT HAVE 7188 04:31:50,996 --> 04:31:52,531 RELATIVELY HIGH RISK IN TERMS OF 7189 04:31:52,531 --> 04:31:56,001 SIDE EFFECTS, IT IS HIGHLY 7190 04:31:56,001 --> 04:31:57,202 IMPROBABLE THAT YOU'RE GOING TO 7191 04:31:57,202 --> 04:31:57,803 IMPROVE OUTCOMES HERE. 7192 04:31:57,803 --> 04:31:59,972 TO MY MIND, AT LEAST, IT SEEMS 7193 04:31:59,972 --> 04:32:01,373 NOW ILLOGICAL, HAVING SEEN ALL 7194 04:32:01,373 --> 04:32:02,875 OF THIS DATA, TO INCLUDE BOTH OF 7195 04:32:02,875 --> 04:32:05,377 THESE POPULATIONS INTO THE SAME 7196 04:32:05,377 --> 04:32:10,682 BIOLOGICAL INTERVENTION TRIAL. 7197 04:32:10,682 --> 04:32:12,317 WHAT ARE THE NEXT STEPS FOR 7198 04:32:12,317 --> 04:32:15,254 PHENOTYPE-SPECIFIC TRIALS? 7199 04:32:15,254 --> 04:32:20,092 SO WE'RE WAITING ON THE PHIND 7200 04:32:20,092 --> 04:32:21,426 RESULT WHICH INCLUDES BIOLOGICAL 7201 04:32:21,426 --> 04:32:23,328 FEATURES IN ITS MODEL TO SEE 7202 04:32:23,328 --> 04:32:25,297 WHETHER OR NOT WE CAN DO SOME 7203 04:32:25,297 --> 04:32:26,698 REALTIME PHENOTYPING AT THE 7204 04:32:26,698 --> 04:32:28,066 BEDSIDE. 7205 04:32:28,066 --> 04:32:30,302 CONTINGENT ON THAT AND OTHER 7206 04:32:30,302 --> 04:32:31,570 POTENTIAL AVENUES, THE PANTHER 7207 04:32:31,570 --> 04:32:32,437 CONSORTIUM WHICH IS UP AND 7208 04:32:32,437 --> 04:32:34,840 RUNNING, THIS IS A MULTICENTER 7209 04:32:34,840 --> 04:32:35,707 INTERNATIONAL CONSORTIUM WHICH 7210 04:32:35,707 --> 04:32:37,409 IS TRYING TO DO PRECISION 7211 04:32:37,409 --> 04:32:40,579 MEDICINE, ADAPTIVE TRIALS IN 7212 04:32:40,579 --> 04:32:42,314 HYPOXEMIC ACUTE RESPIRATORY 7213 04:32:42,314 --> 04:32:44,016 FAILURE BUT WITH A VIEW TO 7214 04:32:44,016 --> 04:32:45,884 EXPANDING IT, THIS IS BASED ON 7215 04:32:45,884 --> 04:32:47,953 OUR PHENOTYPING SCHEMA, 7216 04:32:47,953 --> 04:32:53,692 EXPANDING IT TO POTENTIALLY -- 7217 04:32:53,692 --> 04:32:58,230 THE FINE TECHNOLOGY TO DO A 7218 04:32:58,230 --> 04:32:59,331 RANDOMIZED TRIAL OF PATIENTS 7219 04:32:59,331 --> 04:33:01,900 WITH ACUTE HYPOXIC RESPIRATORY 7220 04:33:01,900 --> 04:33:02,634 FAILURE AND SEPSIS. 7221 04:33:02,634 --> 04:33:04,603 SO WHAT ABOUT THE CLINICAL 7222 04:33:04,603 --> 04:33:05,203 CLASSIFIER MODEL? 7223 04:33:05,203 --> 04:33:07,172 DOES IT HAVE VALIDITY FOR 7224 04:33:07,172 --> 04:33:08,040 CLINICAL DECISION-MAKING AND ALL 7225 04:33:08,040 --> 04:33:09,141 OF THE THINGS THAT DR. O'BRIEN 7226 04:33:09,141 --> 04:33:11,276 AND HOLDER TALKED ABOUT, THAT WE 7227 04:33:11,276 --> 04:33:13,545 ARE LOOKING TO IMPLEMENT THIS 7228 04:33:13,545 --> 04:33:15,514 INTO THE EHR AND STUDY THIS 7229 04:33:15,514 --> 04:33:16,848 PROSPECTIVELY AND WE WILL FACE 7230 04:33:16,848 --> 04:33:19,151 THE STANDARD SKEPTICISM, BUTLY 7231 04:33:19,151 --> 04:33:20,819 SAY THE MODEL PERFORMANCE 7232 04:33:20,819 --> 04:33:25,090 METRICS ARE AMAZING AUCs OF .9 I 7233 04:33:25,090 --> 04:33:26,224 THINK I'M GREAT AT TRAINING 7234 04:33:26,224 --> 04:33:28,126 MODELS OR THAT XG BOOST IS 7235 04:33:28,126 --> 04:33:29,494 TERRIFIC, BUT ACTUALLY I DO 7236 04:33:29,494 --> 04:33:31,029 GENUINELY BELIEVE THAT IF YOU 7237 04:33:31,029 --> 04:33:33,365 SEEK DISCRETE BIOLOGICAL DISEASE 7238 04:33:33,365 --> 04:33:34,266 STATES, YOUR MODELS WILL WORK 7239 04:33:34,266 --> 04:33:36,034 MUCH MORE BETTER. 7240 04:33:36,034 --> 04:33:37,869 AS LONG AS YOU HAVE THE RIGHT 7241 04:33:37,869 --> 04:33:38,837 FEATURES THAT PREDICT THOSE 7242 04:33:38,837 --> 04:33:41,206 SPECIFIC DISEASE STATES. 7243 04:33:41,206 --> 04:33:42,507 THEN THE OTHER QUESTION IS, OF 7244 04:33:42,507 --> 04:33:43,842 COURSE, WHAT INTERVENTIONS DO WE 7245 04:33:43,842 --> 04:33:44,476 TEST? 7246 04:33:44,476 --> 04:33:46,211 I THINK ACTIVATED PROTEIN C 7247 04:33:46,211 --> 04:33:47,946 WOULD BE A PRETTY GOOD TEST FOR 7248 04:33:47,946 --> 04:33:49,348 THE HYPERINFLAMMATORY PHENOTYPE. 7249 04:33:49,348 --> 04:33:51,783 HOWEVER, I THINK OUR OWN FIELD 7250 04:33:51,783 --> 04:33:52,451 UNFORTUNATELY HAS BEEN BURNED 7251 04:33:52,451 --> 04:33:53,852 WITH THAT PARTICULAR 7252 04:33:53,852 --> 04:33:54,653 INTERVENTION. 7253 04:33:54,653 --> 04:33:58,023 SO WE HAVE -- WE'RE CURRENTLY 7254 04:33:58,023 --> 04:34:02,761 DECIDING IF THE PANTHER TRIAL 7255 04:34:02,761 --> 04:34:09,434 GOES AHEAD WHICH WE USE. 7256 04:34:09,434 --> 04:34:10,635 FIRST WE NEED TO CHARACTERIZE 7257 04:34:10,635 --> 04:34:12,337 THE HOST RESPONSE USING 7258 04:34:12,337 --> 04:34:13,105 BIOLOGICAL MEASUREMENTS. 7259 04:34:13,105 --> 04:34:15,807 A QUICK PLUG TO CHECK OUT THE 7260 04:34:15,807 --> 04:34:18,710 APS CONSORTIUM FUNDED BY THE 7261 04:34:18,710 --> 04:34:19,011 NHLBI. 7262 04:34:19,011 --> 04:34:20,479 NEXT IS TO USE MACHINE LEARNING 7263 04:34:20,479 --> 04:34:22,781 TO TRY AND IDENTIFY MORE 7264 04:34:22,781 --> 04:34:23,548 BIOLOGICALLY HOMOGENEOUS 7265 04:34:23,548 --> 04:34:25,417 SUBGROUPS, AND THEN TRANSLATE TO 7266 04:34:25,417 --> 04:34:26,618 THE BEDSIDE. 7267 04:34:26,618 --> 04:34:28,887 FOR SUBGROUPS THAT ARE ROBUST, I 7268 04:34:28,887 --> 04:34:31,890 DO BRI BELIEVE WE NEED TO GO BAO 7269 04:34:31,890 --> 04:34:34,126 ANIMAL MODELS AND TRY YOU AND 7270 04:34:34,126 --> 04:34:35,394 STAND ITS PATHOPHYSIOLOGY, 7271 04:34:35,394 --> 04:34:36,328 BETTER UNDERSTAND THE ROLE OF 7272 04:34:36,328 --> 04:34:37,829 PATHOGEN AND HOST FOR 7273 04:34:37,829 --> 04:34:38,663 PRECISION-BASED CARE. 7274 04:34:38,663 --> 04:34:43,035 AND ALSO TO STUDY IMMUNOLOGICAL 7275 04:34:43,035 --> 04:34:44,536 CHANGES IN THE HEALTH AND 7276 04:34:44,536 --> 04:34:46,571 DISEASE WITH AGING AND THIS IS 7277 04:34:46,571 --> 04:34:50,275 SORT OF THE -- THIS FAR OUT KIND 7278 04:34:50,275 --> 04:34:52,611 OF STAR TREKY TYPE VISION THAT 7279 04:34:52,611 --> 04:34:54,212 I'M SORT OF ENGAGING WITH, IS 7280 04:34:54,212 --> 04:34:56,014 THAT IF WE CAN PREVENT PEOPLE 7281 04:34:56,014 --> 04:34:58,316 FROM GETTING SEPSIS AND OTHER 7282 04:34:58,316 --> 04:34:59,951 METHODS THAT WE CAN -- OTHER 7283 04:34:59,951 --> 04:35:01,319 APPROACHES THAT WE CAN USE TO 7284 04:35:01,319 --> 04:35:06,224 TRY AND UNDERSTAND THE 7285 04:35:06,224 --> 04:35:07,559 COMMUNITY-BASED EP GENETIC 7286 04:35:07,559 --> 04:35:09,961 INTERACTIONS THAT LEAD PEOPLE TO 7287 04:35:09,961 --> 04:35:11,530 HAVING THESE ABNORMAL RESPONSES 7288 04:35:11,530 --> 04:35:15,167 TO PATHOGENS, THAT WE MIGHT BE 7289 04:35:15,167 --> 04:35:17,102 ABLE TO CORRECT IN THE COMMUNITY 7290 04:35:17,102 --> 04:35:20,672 TO TRY AND PREVENT SEPSIS BEFORE 7291 04:35:20,672 --> 04:35:25,343 IT GETS TO THE ICU. 7292 04:35:25,343 --> 04:35:27,746 SO IN SUMMARY OF THE WORK THAT 7293 04:35:27,746 --> 04:35:29,781 I'VE SHOWN YOU, WE HAVE 7294 04:35:29,781 --> 04:35:31,383 DESCRIBED TWO PHENOTYPES OF 7295 04:35:31,383 --> 04:35:32,951 SEPSIS, THE HYPER AND 7296 04:35:32,951 --> 04:35:34,386 HYPOINFLAMMATORY IN ABOUT 15,000 7297 04:35:34,386 --> 04:35:35,787 PATIENTS. 7298 04:35:35,787 --> 04:35:38,156 30% OF THE HYPER. 7299 04:35:38,156 --> 04:35:41,760 THE HYPER HAS HIGHER -- 7300 04:35:41,760 --> 04:35:43,862 INKREASED ORGAN FAILURE IN THE 7301 04:35:43,862 --> 04:35:44,963 HYPERINFLAMMATORY PHENOTYPE, 7302 04:35:44,963 --> 04:35:50,335 INCREASED BACTEREMIA WITH ENROW 7303 04:35:50,335 --> 04:36:00,545 BACTERIAEA. 7304 04:36:05,650 --> 04:36:10,288 SO WITH THAT, I WILL JUST LEAVE 7305 04:36:10,288 --> 04:36:13,125 A SLIGHT ACKNOWLEDGMENT OF 7306 04:36:13,125 --> 04:36:13,625 DIFFERENT COLLABORATORS. 7307 04:36:13,625 --> 04:36:15,360 THIS IS JUST THE TIP OF THE 7308 04:36:15,360 --> 04:36:16,128 ICEBERG. 7309 04:36:16,128 --> 04:36:17,329 PEOPLE HAVE BEEN GENEROUS 7310 04:36:17,329 --> 04:36:19,064 LENDING THEIR TRIAL DATA AND 7311 04:36:19,064 --> 04:36:21,833 OBSERVATIONAL COHORTS TO CARRY 7312 04:36:21,833 --> 04:36:23,602 OUT OUR INVESTIGATIONS AND 7313 04:36:23,602 --> 04:36:24,903 GRATEFUL TO THE NIH FOR ALL THE 7314 04:36:24,903 --> 04:36:26,338 FUNDING THEY PROVIDED FOR THIS 7315 04:36:26,338 --> 04:36:26,671 RESEARCH. 7316 04:36:26,671 --> 04:36:32,210 I'M HAPPY TO TAKE QUESTIONS. 7317 04:36:32,210 --> 04:36:37,782 >> THANK YOU SO MUCH, DR. SINHA. 7318 04:36:37,782 --> 04:36:38,717 DR. KOUTROULIS -- OH, WE HAVE A 7319 04:36:38,717 --> 04:36:45,690 QUESTION IN THE AUDIENCE. 7320 04:36:45,690 --> 04:36:45,957 DR. LIAW? 7321 04:36:45,957 --> 04:36:47,659 >> THANKS, GREAT PRESENTATION. 7322 04:36:47,659 --> 04:36:49,094 I SAW A QUESTION ON THE 7323 04:36:49,094 --> 04:36:49,694 CLASSIFICATION OF THE 7324 04:36:49,694 --> 04:36:50,028 PHENOTYPES. 7325 04:36:50,028 --> 04:36:51,997 IS THAT BASED ON A SINGLE TIME 7326 04:36:51,997 --> 04:36:52,430 POINT? 7327 04:36:52,430 --> 04:36:55,000 FOR EXAMPLE, AT ICU ADMISSION, 7328 04:36:55,000 --> 04:36:58,270 AND WHAT ABOUT THE TRAJECTORY OF 7329 04:36:58,270 --> 04:36:58,904 SUBSTANCES, WOULD THERE BE 7330 04:36:58,904 --> 04:37:02,574 CHANGE IN THE PHENOTYPE OR IT'S 7331 04:37:02,574 --> 04:37:03,575 A STATIC ASSESSMENT? 7332 04:37:03,575 --> 04:37:05,177 >> THAT IS SUCH A GREAT 7333 04:37:05,177 --> 04:37:08,480 QUESTION. 7334 04:37:08,480 --> 04:37:10,982 THIS IS A HUGE LIMITATION OF THE 7335 04:37:10,982 --> 04:37:12,450 WORK THAT WE'VE -- THAT I'VE 7336 04:37:12,450 --> 04:37:16,488 SHOWN YOU, IS THAT WE HAVE STU 7337 04:37:16,488 --> 04:37:17,722 STUDIED AT CROSS-SECTIONAL TIME 7338 04:37:17,722 --> 04:37:18,356 POINTS. 7339 04:37:18,356 --> 04:37:20,792 AND THESE PHENOTYPES ARE HIGHLY 7340 04:37:20,792 --> 04:37:23,094 DYNAMIC. 7341 04:37:23,094 --> 04:37:24,963 AND WE HAVE SOME EMERGING DATA. 7342 04:37:24,963 --> 04:37:27,165 INITIALLY WE HAD PUT A PAPER OUT 7343 04:37:27,165 --> 04:37:30,135 THAT SHOWED THAT THERE WERE 7344 04:37:30,135 --> 04:37:31,903 QUITE -- THEY WERE QUITE STABLE 7345 04:37:31,903 --> 04:37:32,771 OVER THE LAST 48 HOURS BUT I 7346 04:37:32,771 --> 04:37:34,539 THINK IT'S A MISINTERPRETATION 7347 04:37:34,539 --> 04:37:35,207 ABOUT DATA. 7348 04:37:35,207 --> 04:37:38,376 WE HAVE A PAPER THAT'S CURRENTLY 7349 04:37:38,376 --> 04:37:40,612 UNDER REVIEW, I'VE BEEN ACROSS 7350 04:37:40,612 --> 04:37:41,179 ABOUT 5,000 PATIENTS, WE'VE 7351 04:37:41,179 --> 04:37:42,347 SHOWN THAT THESE ARE HIGHLY 7352 04:37:42,347 --> 04:37:45,951 UNSTABLE AND HOW QUICKLY THE 7353 04:37:45,951 --> 04:37:48,220 HYPERINFLAMMATORY PHENOTYPE 7354 04:37:48,220 --> 04:37:49,854 RESOLVES IS HIGHLY PREDICTIVE. 7355 04:37:49,854 --> 04:37:51,156 ONE OF THE MOST IMPORTANT 7356 04:37:51,156 --> 04:37:52,691 PREDICTIVE FEATURES OF THESE 7357 04:37:52,691 --> 04:37:54,259 PHENOTYPES IS HOW QUICKLY YOU GO 7358 04:37:54,259 --> 04:37:56,895 FROM HYPERTO NOT BEING HYPER IN 7359 04:37:56,895 --> 04:37:58,196 TERMS OF YOUR PROGNOSIS. 7360 04:37:58,196 --> 04:38:02,767 SO IF YOU GO FROM HYPER TO 7361 04:38:02,767 --> 04:38:04,836 HYPOIN THE FIRST 48 HOURS YOUR 7362 04:38:04,836 --> 04:38:06,838 OUT COME IS ALMOST THE SAME AS 7363 04:38:06,838 --> 04:38:07,739 BEING HYPO AT THE START. 7364 04:38:07,739 --> 04:38:09,407 SO THE LONGER YOU SPEND IN THE 7365 04:38:09,407 --> 04:38:13,245 HYPERINFLAMMATORY STATE, THE 7366 04:38:13,245 --> 04:38:13,979 WORSE YOUR OUTCOME IS. 7367 04:38:13,979 --> 04:38:17,082 SO I THINK WE HAVE TO BE VERY 7368 04:38:17,082 --> 04:38:18,516 MINDFUL WHEN WE'RE INTERPRETING 7369 04:38:18,516 --> 04:38:21,019 THIS DATA AND DOING REALTIME 7370 04:38:21,019 --> 04:38:23,722 PHENOTYPING HOW DO WE CONSUME 7371 04:38:23,722 --> 04:38:25,123 THIS INFORMATION ABOUT THE 7372 04:38:25,123 --> 04:38:26,091 TEMPORAL DYNAMICS OF THE 7373 04:38:26,091 --> 04:38:26,358 PHENOTYPE. 7374 04:38:26,358 --> 04:38:29,628 >> THANK YOU. 7375 04:38:29,628 --> 04:38:30,662 >> FANTASTIC. 7376 04:38:30,662 --> 04:38:31,963 WE'RE GOING TO KEEP MOVING AND 7377 04:38:31,963 --> 04:38:33,732 CIRCLE BACK TO SOME OF THESE 7378 04:38:33,732 --> 04:38:35,133 QUESTIONS IN OUR TIME TOGETHER 7379 04:38:35,133 --> 04:38:38,136 LATER. 7380 04:38:38,136 --> 04:38:41,673 IT'S MY PLEASURE TO INTRODUCE 7381 04:38:41,673 --> 04:38:42,474 DR. BIHORAC, SENIOR ASSOCIATE 7382 04:38:42,474 --> 04:38:43,308 DEAN FOR RESEARCH AT THE 7383 04:38:43,308 --> 04:38:44,342 UNIVERSITY OF FLORIDA. 7384 04:38:44,342 --> 04:38:45,343 SHE'S GOING TO SPEAK ON A.I. FOR 7385 04:38:45,343 --> 04:38:50,148 THE FUTURE OF SEPSIS MANAGEMENT. 7386 04:38:50,148 --> 04:38:50,782 TAK IT AWAY. 7387 04:38:50,782 --> 04:38:52,183 >> THANK YOU SO MUCH, VINNY. 7388 04:38:52,183 --> 04:38:55,053 CAN YOU HEAR ME? 7389 04:38:55,053 --> 04:38:55,887 >> YES, WE CAN. 7390 04:38:55,887 --> 04:38:57,389 >> IT'S GREAT TO BE THE LAST 7391 04:38:57,389 --> 04:39:00,091 SPEAKER TALKING ABO ABOUT THE 7392 04:39:00,091 --> 04:39:00,558 FUTURE. 7393 04:39:00,558 --> 04:39:02,494 IT'S REALLY A GREAT DAY, I 7394 04:39:02,494 --> 04:39:04,195 LEARNED SO MUCH, EXCITED TO BE 7395 04:39:04,195 --> 04:39:07,365 TOGETHER, LIKE-MINDED RESEARCHER 7396 04:39:07,365 --> 04:39:09,934 SCIENTISTS. 7397 04:39:09,934 --> 04:39:10,802 I APOLOGIZE THAT I DID NOT PUT 7398 04:39:10,802 --> 04:39:12,003 MY DISCLOSURES. 7399 04:39:12,003 --> 04:39:13,738 I DO NOT HAVE ANY CONFLICT 7400 04:39:13,738 --> 04:39:16,541 EXCEPT MY FUNDING FROM NIH. 7401 04:39:16,541 --> 04:39:18,143 SO I WANT TO THINK BUS FRAMEWORK 7402 04:39:18,143 --> 04:39:19,277 ABOUT HOW WE THINK RIGHT NOW 7403 04:39:19,277 --> 04:39:21,780 THAT OUR PREDETION -- OUR MENTAL 7404 04:39:21,780 --> 04:39:23,415 MODEL AROUND SEPSIS GOES FROM 7405 04:39:23,415 --> 04:39:26,151 CAN WE ANTICIPATE OR PREDICT 7406 04:39:26,151 --> 04:39:28,320 RESOURCE SEPSIS AND HOW WE 7407 04:39:28,320 --> 04:39:28,953 DIAGNOSE IT AS SOON AS POSSIBLE 7408 04:39:28,953 --> 04:39:30,889 AND THEN MOVING TO THE 7409 04:39:30,889 --> 04:39:35,593 TREATMENT. 7410 04:39:35,593 --> 04:39:37,896 SO IN THAT KIND OF FRAMEWORK, 7411 04:39:37,896 --> 04:39:40,365 WHAT CAN A.I. BRING IN TERMS OF 7412 04:39:40,365 --> 04:39:43,868 ENRICHING OUR APPROACH TO SEPSIS 7413 04:39:43,868 --> 04:39:45,470 PATIENTS. 7414 04:39:45,470 --> 04:39:46,805 I FIRMLY BELIEVE IN PREVENTION. 7415 04:39:46,805 --> 04:39:48,907 IF WE FOCUS ON TWO MAJOR TYPES 7416 04:39:48,907 --> 04:39:49,741 OF SEPSIS, COMMUNITY ACQUIRED 7417 04:39:49,741 --> 04:39:51,643 AND IN MY OPINION IS A VERY 7418 04:39:51,643 --> 04:39:54,713 IMPORTANT SUBTYPE OF SEPSIS. 7419 04:39:54,713 --> 04:39:56,514 AND HOSPITAL ACQUIRED WE HAVE 7420 04:39:56,514 --> 04:39:57,615 FOCUSED MOSTLY FOR NOW BECAUSE 7421 04:39:57,615 --> 04:39:58,950 THEY HAVE MOSTLY DATA IN THE 7422 04:39:58,950 --> 04:40:00,518 HOSPITAL, WE NEED TO START 7423 04:40:00,518 --> 04:40:02,721 THINKING ABOUT HOW DATA CAN BE 7424 04:40:02,721 --> 04:40:07,292 GENERATED IN BOTH SETTINGS 7425 04:40:07,292 --> 04:40:09,594 TOWARDS TRUE PREDICTION TOWARDS 7426 04:40:09,594 --> 04:40:10,662 FULLY BLOWN SEPSIS. 7427 04:40:10,662 --> 04:40:14,165 AND MOVING TO DIAGNOSIS, HOW CAN 7428 04:40:14,165 --> 04:40:16,234 A.I. HELP US GET MORE PRECISE, 7429 04:40:16,234 --> 04:40:19,504 MORE BIOLOGICALLY ACCURATE 7430 04:40:19,504 --> 04:40:21,239 DIAGNOSIS AS OUR PRIOR SPEAKER 7431 04:40:21,239 --> 04:40:21,906 ELOQUENTLY BROUGHT FORWARD. 7432 04:40:21,906 --> 04:40:23,508 I THINK WE ARE DESPERATELY 7433 04:40:23,508 --> 04:40:27,178 NEEDING MORE TREATMENTS AND 7434 04:40:27,178 --> 04:40:29,047 RECOVERY ENHANCING STRATEGIES 7435 04:40:29,047 --> 04:40:30,448 THAT AT THIS TIME ARE REALLY 7436 04:40:30,448 --> 04:40:31,983 LIMITED AND EVENTUALLY 7437 04:40:31,983 --> 04:40:33,118 MONITORING, BUT MONITORING OF 7438 04:40:33,118 --> 04:40:35,120 THE PATIENTS CAN HELP US 7439 04:40:35,120 --> 04:40:35,987 LONGITUDINALLY PREDICT NOT ONLY 7440 04:40:35,987 --> 04:40:38,423 TO HAVE WHAT HAPPENS TODAY BUT 7441 04:40:38,423 --> 04:40:39,724 WHAT HAPPENS THREE MONTHS LATER 7442 04:40:39,724 --> 04:40:41,693 OR ONE YEAR AFTERWARDS AS WE ALL 7443 04:40:41,693 --> 04:40:44,796 KNOW THAT SEPSIS DOES NOT END AT 7444 04:40:44,796 --> 04:40:46,698 THE HOSPITAL DISCHARGE. 7445 04:40:46,698 --> 04:40:49,534 AND THEN THAT KIND OF 7446 04:40:49,534 --> 04:40:50,735 LONGITUDINALLITY APPROACH, 7447 04:40:50,735 --> 04:40:53,538 SCALING, WE NEED TO GO FROM ONE 7448 04:40:53,538 --> 04:40:54,372 INDIVIDUAL PATIENT AND SCALE 7449 04:40:54,372 --> 04:40:55,607 REALLY OUR APPROACH FROM 7450 04:40:55,607 --> 04:40:57,242 HEALTHCARE SITUATION TO LEARNING 7451 04:40:57,242 --> 04:41:01,613 HEALTH SYSTEMS, STATES, NATION 7452 04:41:01,613 --> 04:41:02,781 AND MAYBE GLOBAL ABILITY TO SEE 7453 04:41:02,781 --> 04:41:04,616 WHAT'S HAPPENING ON A GLOBAL 7454 04:41:04,616 --> 04:41:10,989 SCALE WITH SEPSIS. 7455 04:41:10,989 --> 04:41:13,391 SO I WAS JUST GOING TO REVIEW A 7456 04:41:13,391 --> 04:41:14,592 COUPLE THINGS MANY OF YOU HAVE 7457 04:41:14,592 --> 04:41:16,161 MENTIONED, WE HAVE THE FIRST 7458 04:41:16,161 --> 04:41:17,362 FDA-APPROVED MODEL FOR SEPSIS 7459 04:41:17,362 --> 04:41:24,536 PREDICTION IN HOSPITAL 7460 04:41:24,536 --> 04:41:27,705 IMMUNOSCORE. 7461 04:41:27,705 --> 04:41:32,944 AMONG MANY STUDIES HERE IS A.I. 7462 04:41:32,944 --> 04:41:36,981 MODEL IN HOSPITAL WAS DEPLOYED 7463 04:41:36,981 --> 04:41:38,349 FOR EXPERIMENTAL CLINICAL STUDY 7464 04:41:38,349 --> 04:41:40,418 AND SHOWED SOME REDUCTION IN 7465 04:41:40,418 --> 04:41:42,187 MORTALITY PRE AND POST 7466 04:41:42,187 --> 04:41:42,954 IMPLEMENTATION ANALYSIS USING 7467 04:41:42,954 --> 04:41:46,691 DEEP LEARNING MODEL AND REALLY 7468 04:41:46,691 --> 04:41:48,026 WITH SOME EXPLAINABILITY AND 7469 04:41:48,026 --> 04:41:50,762 PROJECTING ACTUALLY WHO MIGHT 7470 04:41:50,762 --> 04:41:54,232 DEVELOP SEPSIS. 7471 04:41:54,232 --> 04:41:55,733 BUT WHAT ABOUT COMMUNITY 7472 04:41:55,733 --> 04:41:56,401 ACQUIRED SEPSIS? 7473 04:41:56,401 --> 04:41:59,237 WELL, I WANT TO ARGUE THAT THE 7474 04:41:59,237 --> 04:42:00,605 FIRST STEP IN A PREDICTION 7475 04:42:00,605 --> 04:42:04,809 STAGE, WITH HE NEED TO FOCUS ON 7476 04:42:04,809 --> 04:42:09,981 GETTING MORE DEPS D DENSE DATA E 7477 04:42:09,981 --> 04:42:12,617 ARE SOME VIEWS OF THE WEARABLE 7478 04:42:12,617 --> 04:42:13,284 BIOSENSORS AT HOME EVEN BEFORE 7479 04:42:13,284 --> 04:42:14,719 YOU COME TO HOSPITAL, WHETHER 7480 04:42:14,719 --> 04:42:18,223 YOU WILL BE ABLE TO ACTUALLY 7481 04:42:18,223 --> 04:42:19,657 CAPTURE YOUR SYMPTOMS BEFORE YOU 7482 04:42:19,657 --> 04:42:21,526 EVEN DEVELOP FULL BLOWN EITHER 7483 04:42:21,526 --> 04:42:22,260 INFECTION OR SEPSIS. 7484 04:42:22,260 --> 04:42:27,265 THIS IS SOME DATA FROM THE USE 7485 04:42:27,265 --> 04:42:30,568 OF VARIABLES IN DEGENERATIVE 7486 04:42:30,568 --> 04:42:32,737 DISEASE OR PARKINSON'S DISEASE, 7487 04:42:32,737 --> 04:42:34,539 ANOTHER BIG DISEASE WOULD BE 7488 04:42:34,539 --> 04:42:36,608 CONGENITAL HEART DISEASE, AGAIN, 7489 04:42:36,608 --> 04:42:39,244 YOU HAVE AN ENTIRE SPECTRUM OF 7490 04:42:39,244 --> 04:42:42,146 DIFFERENT BIOSENSORS, RIGHT NOW 7491 04:42:42,146 --> 04:42:44,115 MAINLY FOCUSED ON PHYSIOLOGICAL 7492 04:42:44,115 --> 04:42:45,550 PARAMETERS BUT A LOT OF UNTAPPED 7493 04:42:45,550 --> 04:42:46,718 POTENTIAL FOR THAT, BOTH IN 7494 04:42:46,718 --> 04:42:48,686 HOSPITAL AND I THINK ESPECIALLY 7495 04:42:48,686 --> 04:42:51,856 OUTSIDE OF THE HOSPITAL. 7496 04:42:51,856 --> 04:42:53,892 AND WHAT IS MOST EXCITING FOR 7497 04:42:53,892 --> 04:42:56,294 ME, WE ARE APPROACHING THE ERA 7498 04:42:56,294 --> 04:42:59,130 OF COMPLETELY DIFFERENT NEXT 7499 04:42:59,130 --> 04:43:00,031 GENERATION SENSORS THAT CAN NOW 7500 04:43:00,031 --> 04:43:02,600 WATCH MANY MORE THINGS, FROM 7501 04:43:02,600 --> 04:43:03,801 GASTROINTESTINAL TRACT 7502 04:43:03,801 --> 04:43:05,336 METABOLITES TO SWEAT SENSING 7503 04:43:05,336 --> 04:43:07,038 PLATFORMS FOR CHEMICAL ANALYSIS 7504 04:43:07,038 --> 04:43:09,908 TO EVEN MOBILE BIOADHESIVE 7505 04:43:09,908 --> 04:43:11,075 ULTRASOUND THAT CAN GIVE US 7506 04:43:11,075 --> 04:43:14,345 ACTUAL IMAGING IN REALTIME. 7507 04:43:14,345 --> 04:43:15,747 SO I THINK THAT'S ANOTHER REALLY 7508 04:43:15,747 --> 04:43:17,515 EXCITING AREA THAT WE WILL SEE A 7509 04:43:17,515 --> 04:43:21,152 LOT OF MOVEMENT. 7510 04:43:21,152 --> 04:43:23,454 I THINK WHAT I CALL IT 7511 04:43:23,454 --> 04:43:24,022 MULTIDIMENSIONAL BIOHACKING. 7512 04:43:24,022 --> 04:43:25,690 SO I THINK IN OUR CURRENT 7513 04:43:25,690 --> 04:43:28,660 APPROACH, WE ARE LACKING 7514 04:43:28,660 --> 04:43:32,463 DIMENSIONS BOTH IN A SCALE AND 7515 04:43:32,463 --> 04:43:33,898 IN THE -- HOW WIDE THEY ARE. 7516 04:43:33,898 --> 04:43:37,468 HERE IS AN EXCITING STUDY 7517 04:43:37,468 --> 04:43:40,638 FROM -- A NASA TWIN STUDY FROM 7518 04:43:40,638 --> 04:43:42,907 TWO IDENTICAL BROTHERS, MANY OF 7519 04:43:42,907 --> 04:43:46,511 YOU HAVE READ THE STUDY IN 2019, 7520 04:43:46,511 --> 04:43:48,246 PRO FILING OF TWO BROTHERS, ONE 7521 04:43:48,246 --> 04:43:50,415 STAYING ON EARTH, ONE GOING INTO 7522 04:43:50,415 --> 04:43:54,886 SPACE AND NOT ONLY -- HIGHLY 7523 04:43:54,886 --> 04:43:56,621 DENSE DATA, SHOWED SOME REALLY 7524 04:43:56,621 --> 04:43:57,722 EXCITING CHANGES THAT ARE 7525 04:43:57,722 --> 04:44:03,127 HAPPENING ON VERY GRANULAR LEVEL 7526 04:44:03,127 --> 04:44:04,596 IN THE HUMANS ONCE THEY LAUNCH 7527 04:44:04,596 --> 04:44:04,996 TO SPACE. 7528 04:44:04,996 --> 04:44:07,031 SO THIS MULTIDIMENSIONAL 7529 04:44:07,031 --> 04:44:08,032 BIOHACKING NOW HAVE ANOTHER 7530 04:44:08,032 --> 04:44:09,434 DIMENSION AND IT'S ONE I THINK 7531 04:44:09,434 --> 04:44:11,069 THE ERA, THE NEXT 10 YEARS WILL 7532 04:44:11,069 --> 04:44:14,439 BE ALL ABOUT N EQUAL 1ISM, GOING 7533 04:44:14,439 --> 04:44:15,840 FROM THE CENTRAL PLACE OF A 7534 04:44:15,840 --> 04:44:18,509 HOSPITAL OR THE PLACE WHERE WE 7535 04:44:18,509 --> 04:44:21,379 GATHER MORE TO THE HOMES 7536 04:44:21,379 --> 04:44:22,213 INDIVIDUAL PATIENTS WHERE WE CAN 7537 04:44:22,213 --> 04:44:23,648 TRACK OURSELVES, THESE ARE ALL 7538 04:44:23,648 --> 04:44:25,650 MY SENSORS THAT I HAVE CHECKING 7539 04:44:25,650 --> 04:44:27,685 MYSELF, YOU ARE HAVING NOW, EVEN 7540 04:44:27,685 --> 04:44:32,290 MORE COMMERCIALLY AVAILABLE 7541 04:44:32,290 --> 04:44:32,924 ALGORITHMS THAT WILL JUST TELL 7542 04:44:32,924 --> 04:44:34,392 YOU WHEN YOU AREN'T FEELING 7543 04:44:34,392 --> 04:44:34,993 WELL. 7544 04:44:34,993 --> 04:44:36,027 I DON'T THINK WE'RE FAR AWAY 7545 04:44:36,027 --> 04:44:36,828 FROM THE HOAMENT THAT WE WOULD 7546 04:44:36,828 --> 04:44:40,431 BE ABLE TO ACTUALLY ?A SIGNAL TO 7547 04:44:40,431 --> 04:44:41,899 OUR PATIENT AT WHICH TIME THEY 7548 04:44:41,899 --> 04:44:43,901 NEED ANTIBIOTICS AND WHICH TIME 7549 04:44:43,901 --> 04:44:46,738 POINT THEY MAYBE NEED TO GO TO 7550 04:44:46,738 --> 04:44:47,839 THE HOSPITAL. 7551 04:44:47,839 --> 04:44:50,308 THIS VERY VAGUE TERM OF THE 7552 04:44:50,308 --> 04:44:52,910 DYSFUNCTIONALLY IMMUNE RESPONSE. 7553 04:44:52,910 --> 04:44:54,779 ADDING TO THE PHYSIOLOGICAL 7554 04:44:54,779 --> 04:44:56,280 MAINLY PHYSIOLOGICAL SIGNALS 7555 04:44:56,280 --> 04:44:58,549 MONITORING THEY'RE GOING TO HAVE 7556 04:44:58,549 --> 04:44:59,550 ENTIRE SPECTRUM OF CHEMICAL OR 7557 04:44:59,550 --> 04:45:07,325 EVEN IMAGING SENSORS. 7558 04:45:07,325 --> 04:45:10,662 WHETHER WE CAN DO SOMETHING LIKE 7559 04:45:10,662 --> 04:45:11,763 THAT EVEN IN HOSPITAL WHERE 7560 04:45:11,763 --> 04:45:13,631 WE'RE VERY MUCH LIMITED NOW ON A 7561 04:45:13,631 --> 04:45:14,966 STRUCTURED CLINICAL DATA, THIS 7562 04:45:14,966 --> 04:45:19,370 IS A STUDY USING A LITTLE BIT OF 7563 04:45:19,370 --> 04:45:21,572 NO STRUCTURE IN THE TEXT, BUT AN 7564 04:45:21,572 --> 04:45:23,241 ENTIRE SECTOR OF IMAGING IS NOTE 7565 04:45:23,241 --> 04:45:24,475 YET PLUGGED IN TO ANY OF THE 7566 04:45:24,475 --> 04:45:25,977 MODELS WE ARE USING AND EVEN 7567 04:45:25,977 --> 04:45:27,912 MORE IMPORTANTLY, MORE 7568 04:45:27,912 --> 04:45:31,315 BIOLOGICAL DATA. 7569 04:45:31,315 --> 04:45:34,485 SO THAT WOULD BE LIKE HOW DO YOU 7570 04:45:34,485 --> 04:45:36,254 IN COMPARISON MOVE TOWARDS 7571 04:45:36,254 --> 04:45:39,190 MULTI-MODALITY BUT THEN YOU NEED 7572 04:45:39,190 --> 04:45:40,458 TO VERTICALLY INTEGRATE ALL OF 7573 04:45:40,458 --> 04:45:43,227 THAT I THINK IN A COMMUNITY 7574 04:45:43,227 --> 04:45:44,462 SETTING, MULTIDIMENSIONAL 7575 04:45:44,462 --> 04:45:46,130 BIOHACKING TO VERTICAL 7576 04:45:46,130 --> 04:45:47,465 CONNECTION WITH THE PROVIDERS 7577 04:45:47,465 --> 04:45:50,501 EITHER TO THE TELEHEALTH OR TO 7578 04:45:50,501 --> 04:45:54,038 THE DIGITAL TWINS OF HOSPITAL OR 7579 04:45:54,038 --> 04:45:55,473 PRACTICES OR SOME SUBSCRIPTION 7580 04:45:55,473 --> 04:45:56,574 SYSTEM THAT LU ACTUALLY BE ABLE 7581 04:45:56,574 --> 04:45:58,910 TO ACT ON WHAT YOU ARE SENSING 7582 04:45:58,910 --> 04:46:01,879 OR DECIDING AS N EQUAL 7583 04:46:01,879 --> 04:46:02,647 1 INDIVIDUAL PATIENT AND I THINK 7584 04:46:02,647 --> 04:46:04,615 WE'RE GOING TO SEE THE 7585 04:46:04,615 --> 04:46:05,383 CENTRALIZATION PERHAPS EVEN ON 7586 04:46:05,383 --> 04:46:06,517 THOSE WHO TAKE CARE OF THESE 7587 04:46:06,517 --> 04:46:07,318 PATIENTS BEFORE THEY COME TO 7588 04:46:07,318 --> 04:46:08,386 HOSPITAL SO THEY NEVER COME TO 7589 04:46:08,386 --> 04:46:08,953 HOSPITAL. 7590 04:46:08,953 --> 04:46:17,228 I WOULD SAY TH THE COMPRESSIONAL 7591 04:46:17,228 --> 04:46:18,429 MORBIDITY, THE BEST APPROACH TO 7592 04:46:18,429 --> 04:46:21,399 GET HEALTHY IS TO NEVER GET 7593 04:46:21,399 --> 04:46:21,833 SICK. 7594 04:46:21,833 --> 04:46:23,468 AND WE WILL BE MORE MOVING 7595 04:46:23,468 --> 04:46:24,969 TOWARDS WHAT WE ARE WORKING -- 7596 04:46:24,969 --> 04:46:27,205 WHAT WE CALL REALTIME AMBIENT 7597 04:46:27,205 --> 04:46:28,372 INTELLIGENCE, MORE TO THE 7598 04:46:28,372 --> 04:46:31,476 HOSPITAL SETTING. 7599 04:46:31,476 --> 04:46:32,577 BESIDES DATA GENERATED THROUGH 7600 04:46:32,577 --> 04:46:35,113 THE CLINICAL CARE, IT CAN BE 7601 04:46:35,113 --> 04:46:36,481 USED OTHER SENSORS AND COLLECT 7602 04:46:36,481 --> 04:46:39,717 DIFFERENT TYPE OF DATA THAT MAY 7603 04:46:39,717 --> 04:46:41,419 MORE AMBULATE HUMAN PERCEPTION. 7604 04:46:41,419 --> 04:46:43,187 AS AN EXAMPLE, NONE OF OUR 7605 04:46:43,187 --> 04:46:44,956 MODELS USE ANY VISUAL CUES. 7606 04:46:44,956 --> 04:46:48,960 AS A PHYSICIAN, WE ENTER 7607 04:46:48,960 --> 04:46:50,061 PATIENT'S -- VISION, SMELL, TO 7608 04:46:50,061 --> 04:46:51,162 REALLY MAKE DECISIONS ABOUT 7609 04:46:51,162 --> 04:46:51,896 WHAT'S HAPPENING TO OUR 7610 04:46:51,896 --> 04:46:52,396 PATIENTS. 7611 04:46:52,396 --> 04:46:56,033 SO WE HAVE USED SENSORS SUCH AS 7612 04:46:56,033 --> 04:46:58,803 RGB INTERNAL CAMERAS, SOME OF 7613 04:46:58,803 --> 04:47:00,905 THE DEPTH CAMERA AND SO ON TO 7614 04:47:00,905 --> 04:47:02,340 DEVELOP THESE SERIES OF DEEP 7615 04:47:02,340 --> 04:47:04,008 LEARNING ALGORITHMS TO DETECT 7616 04:47:04,008 --> 04:47:04,709 CERTAIN CHARACTERISTICS OF THE 7617 04:47:04,709 --> 04:47:05,643 PATIENT REALTIME. 7618 04:47:05,643 --> 04:47:08,746 HERE IS OUR END TO END PLAS FORM 7619 04:47:08,746 --> 04:47:10,381 TO TRACK MOBILITY IN THE ROOM 7620 04:47:10,381 --> 04:47:12,016 WITHOUT ANY HUMAN INPUT SO YOU 7621 04:47:12,016 --> 04:47:14,519 CAN ACTUALLY 24/7 MONITOR 7622 04:47:14,519 --> 04:47:16,821 PATIENT IN THE ROOMS, AND REALLY 7623 04:47:16,821 --> 04:47:20,658 USE THAT DATA TO PREDICT AS 7624 04:47:20,658 --> 04:47:22,059 EXAMPLE MORE BUILT PATTERN, 7625 04:47:22,059 --> 04:47:23,060 ACTIVITY PATTERN, AND I WILL 7626 04:47:23,060 --> 04:47:25,429 SHOW ON THE NEXT SLIDE THESE NOW 7627 04:47:25,429 --> 04:47:26,664 MOVING NOT ONLY FROM OUR 7628 04:47:26,664 --> 04:47:29,133 MOBILITY BUT ALSO THE FACIAL 7629 04:47:29,133 --> 04:47:29,534 EXPRESSION. 7630 04:47:29,534 --> 04:47:34,338 ONE OF OUR APPROACH IS TO USE 7631 04:47:34,338 --> 04:47:38,810 END TO END ACTION UNIT DETECTION 7632 04:47:38,810 --> 04:47:40,244 ON THE FACE WITH VISION 7633 04:47:40,244 --> 04:47:41,679 TRANSFORMER SO YOU CAN ACTUALLY 7634 04:47:41,679 --> 04:47:44,081 COMPOSE HUMAN FACE IN 48 ACTION 7635 04:47:44,081 --> 04:47:44,282 UNIT. 7636 04:47:44,282 --> 04:47:45,783 THESE ACTION UNITS ARE COMBINED 7637 04:47:45,783 --> 04:47:47,785 TO CREATE OUR EMOTIONS, SO A 7638 04:47:47,785 --> 04:47:49,654 COMBINATION OF SOME ACTION UNIT 7639 04:47:49,654 --> 04:47:51,022 EQUALS CERTAIN EMOTIONS. 7640 04:47:51,022 --> 04:47:53,324 SO IN OUR APPROACH, WE ARE NOW 7641 04:47:53,324 --> 04:47:57,361 ACTUALLY ABLE TO AUTONOMOUSLY 7642 04:47:57,361 --> 04:48:01,499 CAPTURE A PATIENT'S FACE IN A 7643 04:48:01,499 --> 04:48:03,334 ROOM FULL OF OTHER HUMANS, TRAP 7644 04:48:03,334 --> 04:48:05,002 THAT FACE IN REALTIME AND ASSESS 7645 04:48:05,002 --> 04:48:08,372 THE ACTIVITY OF CERTAIN ACTION 7646 04:48:08,372 --> 04:48:09,540 AND THEN CORRELATE THEM WITH 7647 04:48:09,540 --> 04:48:10,608 CLINICAL SEVERITY. 7648 04:48:10,608 --> 04:48:13,144 AND HERE'S A VERY SMALL -- HERE 7649 04:48:13,144 --> 04:48:17,782 IS A PLACE WHERE WE USE OUR 7650 04:48:17,782 --> 04:48:20,051 CLINICAL MODEL AND USE TRANSFER 7651 04:48:20,051 --> 04:48:22,153 LEARNING IN OUR SMALLER COHORT 7652 04:48:22,153 --> 04:48:24,388 AND VISUAL CUES, WE CALLED IT 7653 04:48:24,388 --> 04:48:25,990 VISUAL CUES, EACH ACTION UNIT 7654 04:48:25,990 --> 04:48:27,892 WAS INPUTTED IN THE CLINICAL 7655 04:48:27,892 --> 04:48:30,328 MODEL, AND THERE WAS SIGNIFICANT 7656 04:48:30,328 --> 04:48:32,930 IMPROVEMENT IN THE ABILITY TO 7657 04:48:32,930 --> 04:48:34,665 PREDICT THE SEVERITY OF ILLNESS 7658 04:48:34,665 --> 04:48:35,867 AND INCORPORATE THESE VISUAL 7659 04:48:35,867 --> 04:48:37,168 CUES IN THE REGULAR CLINICAL 7660 04:48:37,168 --> 04:48:42,106 MODEL THAT IS CLINICAL DATA. 7661 04:48:42,106 --> 04:48:43,941 JUST PUTTING THAT BACK TO THE 7662 04:48:43,941 --> 04:48:44,909 BEDSIDE, HOW MANY TIMES YOU 7663 04:48:44,909 --> 04:48:45,877 ENTER PATIENT ROOM, TAKE A LOOK 7664 04:48:45,877 --> 04:48:47,612 AT PATIENT AND SAY YOU DON'T 7665 04:48:47,612 --> 04:48:47,879 LOOK GOOD. 7666 04:48:47,879 --> 04:48:48,646 AND I THINK THAT IS SOMETHING 7667 04:48:48,646 --> 04:48:51,449 THAT WE ARE GOING TO BE ABLE TO 7668 04:48:51,449 --> 04:48:52,750 INCORPORATE IN OUR PRACTICE MORE 7669 04:48:52,750 --> 04:48:54,151 AND MORE NOT ONLY THROUGH THE 7670 04:48:54,151 --> 04:48:57,221 VISUAL BUT ALSO OUR ACOUSTIC 7671 04:48:57,221 --> 04:48:58,856 TOOLS, PATIENT VOICES, ALSO 7672 04:48:58,856 --> 04:49:02,526 ENVIRONMENTAL CUES, 7673 04:49:02,526 --> 04:49:06,130 ENVIRONMENTAL TREM T TELEMETRY L 7674 04:49:06,130 --> 04:49:08,566 BECOME PART OF THIS 7675 04:49:08,566 --> 04:49:09,033 DECISION-MAKING. 7676 04:49:09,033 --> 04:49:10,201 BACK TO DIGITAL TWIN, THE IDEA 7677 04:49:10,201 --> 04:49:13,070 THAT WE CAN ACTUALLY USE THIS 7678 04:49:13,070 --> 04:49:15,239 DENSELY MULTI-SCALE SAMPLE 7679 04:49:15,239 --> 04:49:18,609 LONGITUDAL DATA TO KR CREATE SOE 7680 04:49:18,609 --> 04:49:22,213 TWINNING OF THE EXISTING 7681 04:49:22,213 --> 04:49:22,980 PATIENT. 7682 04:49:22,980 --> 04:49:24,048 UNFORTUNATELY FOR THE TRUE 7683 04:49:24,048 --> 04:49:25,016 BIOLOGICAL TWIN, WE NEED TO HAVE 7684 04:49:25,016 --> 04:49:29,620 A DEEPER UNDERSTANDING OF FIRST 7685 04:49:29,620 --> 04:49:30,054 PRINCIPLE. 7686 04:49:30,054 --> 04:49:32,857 MANY COMPLEX PROCESSES IN A 7687 04:49:32,857 --> 04:49:34,292 SEPSIS -- THERE ARE SOME AGENT 7688 04:49:34,292 --> 04:49:35,726 BASED MODELING GROUPS THAT ARE 7689 04:49:35,726 --> 04:49:36,827 WORKING REALLY HARD ON THAT. 7690 04:49:36,827 --> 04:49:38,362 I THINK WE ARE FAR AWAY FROM 7691 04:49:38,362 --> 04:49:39,630 THIS, AND FOR ME, THIS IS ONE OF 7692 04:49:39,630 --> 04:49:42,566 THE BIGGEST -- REALLY THE 7693 04:49:42,566 --> 04:49:44,302 BIGGEST MISSING POINT WHERE WE 7694 04:49:44,302 --> 04:49:46,837 NEED TO COMBINE THESE BIOLOGICAL 7695 04:49:46,837 --> 04:49:48,572 MECHANISTIC MODEL WITH OUR 7696 04:49:48,572 --> 04:49:52,977 CLINICAL MODEL AND REALLY MOVE 7697 04:49:52,977 --> 04:49:54,478 TOWARDS THIS TRUE DIGITAL 7698 04:49:54,478 --> 04:49:59,917 TWINNING. 7699 04:49:59,917 --> 04:50:01,585 NEXT A.I. TREATMENT AND 7700 04:50:01,585 --> 04:50:03,421 RECOVERY, I THINK WE DESPERATELY 7701 04:50:03,421 --> 04:50:05,756 NEED NEW TREATMENTS, HOPEFULLY 7702 04:50:05,756 --> 04:50:07,391 MORE DIGITAL TWINS AND MORE 7703 04:50:07,391 --> 04:50:08,492 DEEPER MULTI-SCALE MODELING CAN 7704 04:50:08,492 --> 04:50:10,394 HELP US FIND NEW TARGETS AND 7705 04:50:10,394 --> 04:50:12,730 TEST THEM, AT THE SAME TIME THE 7706 04:50:12,730 --> 04:50:14,165 NEW THERAPIES NEED PERHAPS 7707 04:50:14,165 --> 04:50:15,800 BETTER PROCESSES, AND THESE 7708 04:50:15,800 --> 04:50:18,402 PROCESSES CAN BE SOMETIMES 7709 04:50:18,402 --> 04:50:20,037 FACILITATED BY USE OF 7710 04:50:20,037 --> 04:50:21,906 REINFORCEMENT LEARNING. 7711 04:50:21,906 --> 04:50:23,607 THIS IS A STUDY FROM MY 7712 04:50:23,607 --> 04:50:25,910 COLLEAGUE AT EMORY WHERE HE USED 7713 04:50:25,910 --> 04:50:27,545 DYNAMICALLY ENFORCING A.I. 7714 04:50:27,545 --> 04:50:31,849 FRAMEWORK TO INCORPORATE 7715 04:50:31,849 --> 04:50:34,418 REALTIME PHYSIOLOGIC DATA -- 7716 04:50:34,418 --> 04:50:35,953 PROCESSES OF CARE BASED ON THESE 7717 04:50:35,953 --> 04:50:37,588 REALTIME INPUTS AND AGAIN THIS 7718 04:50:37,588 --> 04:50:40,725 IS SOMEWHERE IN THE FUTURE. 7719 04:50:40,725 --> 04:50:49,800 SIMILAR STUDY BY KOMOROWSKI TO 7720 04:50:49,800 --> 04:50:53,337 USE OPTIMIZATION OF FLUID -- 7721 04:50:53,337 --> 04:50:54,505 WHERE THE COMBINATION OF 7722 04:50:54,505 --> 04:50:55,906 GRANULAR PHENOTYPING AND 7723 04:50:55,906 --> 04:50:57,308 DECIDING WHAT STATES OR 7724 04:50:57,308 --> 04:50:58,809 PHYSIOLOGICAL STATE OF DISEASE 7725 04:50:58,809 --> 04:51:01,679 YOU MAY BE BASED ON PARAMETERS 7726 04:51:01,679 --> 04:51:03,214 WE COLLECT, AND THEN TRYING TO 7727 04:51:03,214 --> 04:51:07,651 SIGN REALLY OUR FLUID THERAPY 7728 04:51:07,651 --> 04:51:08,953 AND VASOPRESSOR THERAPY BASED ON 7729 04:51:08,953 --> 04:51:10,121 THOSE STATES, AGAIN IT WOULD BE 7730 04:51:10,121 --> 04:51:11,789 IN THE FUTURE, MUCH MORE 7731 04:51:11,789 --> 04:51:13,090 COMPREHENSIVE OR MORE 7732 04:51:13,090 --> 04:51:13,858 BIOLOGICALLY DEEPER 7733 04:51:13,858 --> 04:51:15,593 UNDERSTANDING OF THESE STATES, 7734 04:51:15,593 --> 04:51:17,728 WHAT DO THEY MEAN NOT ONLY ON A 7735 04:51:17,728 --> 04:51:18,996 HOLISTIC LEVEL BUT DIFFERENT 7736 04:51:18,996 --> 04:51:20,398 ORGAN LEVEL AND HOPEFULLY WE 7737 04:51:20,398 --> 04:51:23,768 WILL HAVE MORE THAN JUST SALTY 7738 04:51:23,768 --> 04:51:26,404 WATER AND GOOD AIR TO DELIVER TO 7739 04:51:26,404 --> 04:51:28,372 OUR PATIENTS FOR TREATMENT OF 7740 04:51:28,372 --> 04:51:33,277 SEPSIS. 7741 04:51:33,277 --> 04:51:34,912 AGAIN SIMILAR ANOTHER STUDY THAT 7742 04:51:34,912 --> 04:51:38,849 LOOKED AT USE OF REINFORCEMENT 7743 04:51:38,849 --> 04:51:41,452 LEARNING TO UTILIZE 7744 04:51:41,452 --> 04:51:43,354 CORTICOSTEROID THERAPY, SOME OF 7745 04:51:43,354 --> 04:51:47,124 THESE ENDO TYPES WE'RE ABLE TO 7746 04:51:47,124 --> 04:51:49,193 CLASSIFY PATIENTS WHO MIGHT BE 7747 04:51:49,193 --> 04:51:51,162 STEROID RESPONSIVE, THIS IS NOW 7748 04:51:51,162 --> 04:51:52,329 USING COMPUTATIONAL APPROACHES 7749 04:51:52,329 --> 04:51:58,469 THAT CAN AUTOMATICALLY MAP 7750 04:51:58,469 --> 04:52:01,405 PATIENTS' PHENOTYPE PERHAPS 7751 04:52:01,405 --> 04:52:07,078 TAKING HUMAN FACTOR OUT. 7752 04:52:07,078 --> 04:52:08,412 SO THE FUTURE OF A.I. FOR SEPSIS 7753 04:52:08,412 --> 04:52:10,047 IN ONE SLIDE, I WOULD SAY IT'S A 7754 04:52:10,047 --> 04:52:14,485 FULL STACK OF APPROACH FROM 7755 04:52:14,485 --> 04:52:15,286 PREVENTION TO DIAGNOSIS 7756 04:52:15,286 --> 04:52:16,454 TREATMENT RECOVERY MONITORING 7757 04:52:16,454 --> 04:52:17,988 AND THEN BACK TO PREVENTION, I 7758 04:52:17,988 --> 04:52:22,860 THINK IT NEEDS TO HAPPEN NOT 7759 04:52:22,860 --> 04:52:25,296 ONLY IN THE HOSPITAL, WE NEED TO 7760 04:52:25,296 --> 04:52:27,164 GET OUT OF THE HOSPITAL AT HOME 7761 04:52:27,164 --> 04:52:31,869 IN ANY SETTING, USING MUCH MORE 7762 04:52:31,869 --> 04:52:32,970 THAN CURRENTLY COLLECTED 7763 04:52:32,970 --> 04:52:35,473 CLINICAL DATA, EXPANDED USE OF 7764 04:52:35,473 --> 04:52:37,408 PERVASIVE SENSING, AMBIENT 7765 04:52:37,408 --> 04:52:39,610 INTELLIGENCE AND DEVELOPING AND 7766 04:52:39,610 --> 04:52:43,614 MERGING A LOT OF INSIGHT WE HAVE 7767 04:52:43,614 --> 04:52:46,016 ON ANIMAL MODELS AND MORE 7768 04:52:46,016 --> 04:52:49,753 BIOLOGICAL WORK THAT WAS DONE IN 7769 04:52:49,753 --> 04:52:50,921 SEPSIS MERGING OUR CLINICAL 7770 04:52:50,921 --> 04:52:51,789 UNDERSTANDING OF DISEASE AND 7771 04:52:51,789 --> 04:52:53,324 PUTTING ALL THESE DOTS TOGETHER 7772 04:52:53,324 --> 04:53:00,931 TO CREATE LIKE FULLY EXPLAINABLE 7773 04:53:00,931 --> 04:53:06,437 MMODEL, DYNAMIC MECHANISTIC MODL 7774 04:53:06,437 --> 04:53:08,205 OF SEPSIS THAT IS TRANSLATABLE 7775 04:53:08,205 --> 04:53:09,607 TO CLINICAL PRACTICE. 7776 04:53:09,607 --> 04:53:11,242 I HOPE WE WILL SEE LESS SEPSIS 7777 04:53:11,242 --> 04:53:12,877 THAT EFFICIENTLY WE WILL BE OUT 7778 04:53:12,877 --> 04:53:15,146 OF THE BUSINESS BECAUSE ALL 7779 04:53:15,146 --> 04:53:16,147 SEPSIS WILL NEVER BE SEPSIS, IT 7780 04:53:16,147 --> 04:53:17,448 WILL JUST BE INFECTION THAT WE 7781 04:53:17,448 --> 04:53:18,349 TAKE CARE. 7782 04:53:18,349 --> 04:53:21,018 SO THAT'S MY VISION FOR THE 7783 04:53:21,018 --> 04:53:22,019 FUTURE, WE WILL BE OUT OF THE 7784 04:53:22,019 --> 04:53:22,853 BUSINESS HOPEFULLY. 7785 04:53:22,853 --> 04:53:25,556 THANK YOU. 7786 04:53:25,556 --> 04:53:26,957 >> WONDERFUL. 7787 04:53:26,957 --> 04:53:29,326 WHAT GREAT BLUE SKY FOR US IN 7788 04:53:29,326 --> 04:53:30,294 THE FUTURE THAT WE ARE GOING TO 7789 04:53:30,294 --> 04:53:31,395 BE OUT OF JOBS. 7790 04:53:31,395 --> 04:53:38,636 WHICH WOULD BE GREAT. 7791 04:53:38,636 --> 04:53:40,471 I THINK WE'RE GOING TO TAKE THIS 7792 04:53:40,471 --> 04:53:44,175 TIME TO BRING TOGETHER ALL THE 7793 04:53:44,175 --> 04:53:45,376 PRESENTERS SO WE CAN HAVE SOME 7794 04:53:45,376 --> 04:53:46,377 DISCUSSION AND ADDRESS SOME 7795 04:53:46,377 --> 04:53:56,554 QUESTIONS. 7796 04:53:56,554 --> 04:53:58,055 SO WHILE WE DO THAT, I SEE 7797 04:53:58,055 --> 04:53:59,857 THERE'S A COUPLE QUESTIONS IN 7798 04:53:59,857 --> 04:54:02,626 THE CHAT. 7799 04:54:02,626 --> 04:54:03,961 AND WE CAN GET TO THOSE. 7800 04:54:03,961 --> 04:54:07,431 MAYBE I'LL TURN IT OVER TO 7801 04:54:07,431 --> 04:54:08,933 DR. KOUTROULIS TO KICK US OFF. 7802 04:54:08,933 --> 04:54:10,935 >> YES, THANK YOU, VINNY. 7803 04:54:10,935 --> 04:54:12,770 SO THIS WAS VERY INTERESTING, 7804 04:54:12,770 --> 04:54:15,506 ALL THE SESSIONS WERE REALLY 7805 04:54:15,506 --> 04:54:21,845 AMAZING AND VERY INSIGHTFUL. 7806 04:54:21,845 --> 04:54:23,214 ONE QUESTION FROM THE LAST 7807 04:54:23,214 --> 04:54:24,648 SESSION IS ABOUT THE DIFFERENCES 7808 04:54:24,648 --> 04:54:27,851 AT BASELINE AND IN RESPONSE TO 7809 04:54:27,851 --> 04:54:30,354 TREATMENT AND HOW DIGITAL TWIN, 7810 04:54:30,354 --> 04:54:31,855 YOU KNOW, DIGITAL TWIN WOULD 7811 04:54:31,855 --> 04:54:36,126 TAKE THAT INTO ACCOUNT, LIKE 7812 04:54:36,126 --> 04:54:37,661 PEOPLE HAVE DIFFERENT BASELINE 7813 04:54:37,661 --> 04:54:39,163 CO-MORBID ITS OR PROBLEMS AND 7814 04:54:39,163 --> 04:54:40,030 THEY DON'T MOVE THE SAME WAY. 7815 04:54:40,030 --> 04:54:41,232 THEY'RE VERY DIFFERENT. 7816 04:54:41,232 --> 04:54:42,533 HOW IS THAT ACCOUNTED INTO THE 7817 04:54:42,533 --> 04:54:51,108 MODEL? 7818 04:54:51,108 --> 04:54:53,077 >> VINNY, YOU WANT ME TO TAKE 7819 04:54:53,077 --> 04:54:53,244 IT? 7820 04:54:53,244 --> 04:54:53,811 >> YEAH, SURE. 7821 04:54:53,811 --> 04:54:55,112 WHY DON'T YOU START. 7822 04:54:55,112 --> 04:54:56,413 I THINK HE HAVE BEEN HAS SOME 7823 04:54:56,413 --> 04:54:56,680 THOUGHTS. 7824 04:54:56,680 --> 04:54:58,716 >> I'LL GIVE YOU MY REASON, SO 7825 04:54:58,716 --> 04:55:00,384 LIKE I THINK THAT WE NEED TO GET 7826 04:55:00,384 --> 04:55:04,255 OUT OF OUR MENTALITY THAT ONLY 7827 04:55:04,255 --> 04:55:05,122 THINGS THAT WE KNOW WHAT TO DO 7828 04:55:05,122 --> 04:55:06,790 WITH, WE'RE GOING TO COLLECT, 7829 04:55:06,790 --> 04:55:07,992 BECAUSE THAT'S NOT GOING TO TAKE 7830 04:55:07,992 --> 04:55:09,293 US WHERE WE WANT TO GO. 7831 04:55:09,293 --> 04:55:10,628 THE DATA NEEDS TO BE SO DENSE. 7832 04:55:10,628 --> 04:55:14,231 SO I ENVISION DEEPLY THAT IF YOU 7833 04:55:14,231 --> 04:55:15,666 THINK ABOUT TRUE TWINNING, WHEN 7834 04:55:15,666 --> 04:55:16,400 YOU START GETTING BORN, YOU'RE 7835 04:55:16,400 --> 04:55:18,035 GOING TO BE COMPLETELY SAMPLED. 7836 04:55:18,035 --> 04:55:20,638 LIKE THIS IS -- I'M GOING TO 7837 04:55:20,638 --> 04:55:21,839 OMIC OR IMAGE MYSELF 7838 04:55:21,839 --> 04:55:22,273 CONTINUOUSLY. 7839 04:55:22,273 --> 04:55:25,909 UNTIL WE HIT ENOUGH DATA WITH 7840 04:55:25,909 --> 04:55:26,744 THAT TYPE OF DENSE AT THIS TIME 7841 04:55:26,744 --> 04:55:28,178 THAT YOU CAN START ASKING THESE 7842 04:55:28,178 --> 04:55:29,647 QUESTIONS AND CREATE A REPLICA, 7843 04:55:29,647 --> 04:55:32,082 BECAUSE I CAN MAKE A SKETCH OF 7844 04:55:32,082 --> 04:55:33,684 MYSELF WITH THREE LINES OF A 7845 04:55:33,684 --> 04:55:35,152 BLACK PENCIL BUT THEN I CAN DO 7846 04:55:35,152 --> 04:55:35,986 BEAUTIFUL COLORS, RIGHT? 7847 04:55:35,986 --> 04:55:38,255 SO WE WANT TO COME IN THE MOST 7848 04:55:38,255 --> 04:55:39,657 BEAUTIFUL PAINTING RATHER THAN 7849 04:55:39,657 --> 04:55:42,760 KIND OF ROUGH SKETCH. 7850 04:55:42,760 --> 04:55:44,061 SO WE DON'T HAVE THAT TYPE OF 7851 04:55:44,061 --> 04:55:45,996 DATA, WE HAVE NOT ENOUGH DATA ON 7852 04:55:45,996 --> 04:55:47,331 HEALTHY SUBJECTS. 7853 04:55:47,331 --> 04:55:48,766 WHAT IS WORRISOME FOR ME IS THAT 7854 04:55:48,766 --> 04:55:51,268 WE WILL SEE WITH THE TECHNOLOGY 7855 04:55:51,268 --> 04:55:52,436 DIGITAL DIVIDE MIGHT BE EVEN 7856 04:55:52,436 --> 04:55:53,203 BIGGER BECAUSE PEOPLE WILL HAVE 7857 04:55:53,203 --> 04:55:57,274 A CAPACITY OR ABILITY TO GAIN 7858 04:55:57,274 --> 04:55:58,776 THAT INTENSITY OF DATA. 7859 04:55:58,776 --> 04:55:59,677 MIGHT NOT BE EVERY PERSON EVEN 7860 04:55:59,677 --> 04:56:00,411 IN THIS COUNTRY. 7861 04:56:00,411 --> 04:56:03,047 SO THIS IS GOING TO BE EXPENSIVE 7862 04:56:03,047 --> 04:56:04,114 DIVERGENCE IN WHAT IS ACCESSIBLE 7863 04:56:04,114 --> 04:56:07,718 FOR EVERYONE OR MAYBE FOR -- 7864 04:56:07,718 --> 04:56:09,253 ACCESSIBLE ONLY FOR FEW. 7865 04:56:09,253 --> 04:56:11,088 THAT'S JUST MY VIEW. 7866 04:56:11,088 --> 04:56:12,389 >> GREAT. 7867 04:56:12,389 --> 04:56:14,525 >> ANYONE ELSE WANT TO ADD SOME 7868 04:56:14,525 --> 04:56:22,599 THOUGHTS TO THAT? 7869 04:56:22,599 --> 04:56:23,834 I GUESS I'LL JUST ADD A COMMENT 7870 04:56:23,834 --> 04:56:25,669 WHICH IS WHAT STRUCK ME FROM 7871 04:56:25,669 --> 04:56:27,371 THIS CONVERSATION WAS THAT WE'RE 7872 04:56:27,371 --> 04:56:29,073 TALKING ON MANY DIFFERENT 7873 04:56:29,073 --> 04:56:32,309 RESOLUTIONS AND SCALES SOME OF 7874 04:56:32,309 --> 04:56:34,578 THIS STUFF THAT PRATIK HAS 7875 04:56:34,578 --> 04:56:35,813 GOTTEN INTO IS TRYING TO UNPACK 7876 04:56:35,813 --> 04:56:37,915 THE BIOLOGICAL PROCESSES AND 7877 04:56:37,915 --> 04:56:40,951 THEN CARA IS SPEAKING AT THE 7878 04:56:40,951 --> 04:56:43,253 HUMAN LAYER OF INTERVENTION THAT 7879 04:56:43,253 --> 04:56:46,423 IS REALLY LIKE SOCIOTECHNICAL, 7880 04:56:46,423 --> 04:56:50,994 NOT BIOLOGIC AND THEN I THINK 7881 04:56:50,994 --> 04:56:52,363 ANDRE YOU'VE ADDRESSED SOME OF 7882 04:56:52,363 --> 04:56:53,630 THAT TRANSLATION, WHAT ARE WE 7883 04:56:53,630 --> 04:56:58,102 CAPTURING AND HOW DO WE LEVERAGE 7884 04:56:58,102 --> 04:56:59,503 EHR DATA WHICH IS A PROXY OF 7885 04:56:59,503 --> 04:57:02,806 SOME TREATMENT, SOME BIOLOGIC 7886 04:57:02,806 --> 04:57:04,074 PROCESSES, WHATEVER, THEN AZRA, 7887 04:57:04,074 --> 04:57:05,976 WERE YOU TALKING, I MEAN, LIKE 7888 04:57:05,976 --> 04:57:09,713 INSTRUMENTING THE ENTIRE THING, 7889 04:57:09,713 --> 04:57:11,448 BOTH TEMPORALLY AND WITH 7890 04:57:11,448 --> 04:57:13,717 EXPANSIVE MULTIMODAL CAPTURE. 7891 04:57:13,717 --> 04:57:16,253 WE DON'T EVEN HAVE DEPTH IN ONE 7892 04:57:16,253 --> 04:57:17,988 VERTICAL TODAY, I WOULD SAY, YOU 7893 04:57:17,988 --> 04:57:20,624 KNOW, AND SO THAT VISION -- AND 7894 04:57:20,624 --> 04:57:22,126 PART OF THAT CHALLENGE IS HOW DO 7895 04:57:22,126 --> 04:57:24,895 WE TURN THE DIAL ON THE 7896 04:57:24,895 --> 04:57:26,130 RESOLUTION, BOTH WITH RESPECT TO 7897 04:57:26,130 --> 04:57:28,165 ANY ONE OF THOSE MULTIMODAL 7898 04:57:28,165 --> 04:57:29,466 ASPECTS BUT ALSO WITH RESPECT TO 7899 04:57:29,466 --> 04:57:31,869 THE TRAJECTORY OF ILLNESS BOTH 7900 04:57:31,869 --> 04:57:33,404 IN THE PRESEPSIS PHASE AND THEN 7901 04:57:33,404 --> 04:57:37,241 THROUGH KIND OF LIKE THAT 7902 04:57:37,241 --> 04:57:38,108 TRANSITION. 7903 04:57:38,108 --> 04:57:39,410 SO I WONDER IF ANYONE HAS 7904 04:57:39,410 --> 04:57:44,748 THOUGHTS ON WHAT DO WE TACKLE 7905 04:57:44,748 --> 04:57:45,749 STRATEGICALLY AS WE MOVE 7906 04:57:45,749 --> 04:57:50,754 FORWARD? 7907 04:57:50,754 --> 04:57:52,322 >> I'M GOING TO STEP IN BUT 7908 04:57:52,322 --> 04:57:58,095 MOSTLY RAMBLING THROUGH MY VERY 7909 04:57:58,095 --> 04:57:59,296 BIASED PERSPECTIVES. 7910 04:57:59,296 --> 04:58:01,064 I DON'T KNOW, I'VE BEEN A 7911 04:58:01,064 --> 04:58:02,065 PRACTICING INTENSIVIST NOW FOR 7912 04:58:02,065 --> 04:58:02,332 20 YEARS. 7913 04:58:02,332 --> 04:58:04,168 I DON'T KNOW WHAT SEPSIS MEANS. 7914 04:58:04,168 --> 04:58:08,138 AND I THINK THAT'S A FUND MENTAL 7915 04:58:08,138 --> 04:58:09,339 PROBLEM THAT WE NEED TO GET 7916 04:58:09,339 --> 04:58:09,673 AROUND. 7917 04:58:09,673 --> 04:58:13,243 IT'S NOT EVEN THAT COMPLICATED. 7918 04:58:13,243 --> 04:58:14,678 WE CAN BREAK IT DOWN THROUGH A 7919 04:58:14,678 --> 04:58:17,014 NUMBER OF TANGIBLE POTENTIALLY 7920 04:58:17,014 --> 04:58:18,415 CLINICALLY INTUITIVE WAYS BUT WE 7921 04:58:18,415 --> 04:58:23,887 JUST HAVE TO AT THE OUTSET HELP 7922 04:58:23,887 --> 04:58:25,622 BROADER POPULATIONS TO BE 7923 04:58:25,622 --> 04:58:27,925 CAPTURED IN SUBSEGMENTS. 7924 04:58:27,925 --> 04:58:29,293 AND YOU KNOW, I'VE BEEN 7925 04:58:29,293 --> 04:58:30,194 FORTUNATE ENOUGH TO WORK IN THE 7926 04:58:30,194 --> 04:58:34,031 ED AND IN THE ICU, AND THEY ARE 7927 04:58:34,031 --> 04:58:35,165 FUNDAMENTALLY VERY DIFFERENT 7928 04:58:35,165 --> 04:58:37,334 SPACES. 7929 04:58:37,334 --> 04:58:38,836 EVEN JUST BREAKING IT DOWN 7930 04:58:38,836 --> 04:58:41,238 THROUGH THOSE DOMAINS WILL 7931 04:58:41,238 --> 04:58:44,374 PROVIDE US A RI LITTLE BIT OF 7932 04:58:44,374 --> 04:58:45,742 VALIDITY AND HOMOGENEITY WHICH 7933 04:58:45,742 --> 04:58:46,910 WE CAN THEN STUDY. 7934 04:58:46,910 --> 04:58:50,180 I NOTICED THAT CORA IS A 7935 04:58:50,180 --> 04:58:51,048 HOSPITALIST AND HER TAKE OF 7936 04:58:51,048 --> 04:58:55,118 SEPSIS IS PROBABLY MUCH EARLIER 7937 04:58:55,118 --> 04:58:57,187 AND HAS VERY DIFFERENT OUTCOMES 7938 04:58:57,187 --> 04:59:02,092 AND INTERESTS THAN WHAT I'M JUST 7939 04:59:02,092 --> 04:59:03,627 AS AN INTENSIVIST SEES. 7940 04:59:03,627 --> 04:59:05,362 SO I THINK THAT IS A FUNDAMENTAL 7941 04:59:05,362 --> 04:59:08,432 PROBLEM THAT WE NEED TO TRY AND 7942 04:59:08,432 --> 04:59:11,034 GET OVER, AND AT THE SAME TIME, 7943 04:59:11,034 --> 04:59:12,569 I THINK THERE HAS NEVER BEEN A 7944 04:59:12,569 --> 04:59:14,438 BETTER TIME TO BE ALIVE TO BE A 7945 04:59:14,438 --> 04:59:15,806 SEPSIS RESEARCHER. 7946 04:59:15,806 --> 04:59:18,542 BECAUSE WE DO -- AND YOU KNOW, I 7947 04:59:18,542 --> 04:59:20,410 AGREE WITH WHAT AZRA SAID, THAT 7948 04:59:20,410 --> 04:59:21,812 WE HAVEN'T COLLECTED THE DATA 7949 04:59:21,812 --> 04:59:24,114 THAT WE NEED TO, BUT WE'RE 7950 04:59:24,114 --> 04:59:25,549 DEFINITELY FURTHER ALONG IN OUR 7951 04:59:25,549 --> 04:59:27,751 JOURNEY AND THERE ARE THESE 7952 04:59:27,751 --> 04:59:30,120 MULTIMODAL DATA THAT I HAVE 7953 04:59:30,120 --> 04:59:31,755 ACCESS TO WHICH LIKE 15 YEARS 7954 04:59:31,755 --> 04:59:33,390 AGO I COULDN'T EVEN DREAM. 7955 04:59:33,390 --> 04:59:35,792 AND I THINK THAT IS WHERE THE 7956 04:59:35,792 --> 04:59:37,094 OPPORTUNITY LIES, AND WHERE WE 7957 04:59:37,094 --> 04:59:42,032 CAN START BREAKING THEM DOWN FOO 7958 04:59:42,032 --> 04:59:44,668 PATHOGEN AND HOST RESPONSE 7959 04:59:44,668 --> 04:59:48,372 INTERACTIONS THAT ARE MEANINGFUL 7960 04:59:48,372 --> 04:59:50,340 AND POTENTIALLY 7961 04:59:50,340 --> 04:59:51,642 TREATMENT-RESPONSIVE AND TURNING 7962 04:59:51,642 --> 04:59:54,278 SEPSIS INTO DISEASE RATHER THAN 7963 04:59:54,278 --> 04:59:54,745 WHAT IT IS RIGHT NOW. 7964 04:59:54,745 --> 04:59:58,715 >> I THINK I'LL STEP IN ALSO. 7965 04:59:58,715 --> 05:00:02,586 BUT TO ADD TO THAT, I THINK ONE 7966 05:00:02,586 --> 05:00:05,055 OF THE REASONS WHY IT'S A GREAT 7967 05:00:05,055 --> 05:00:06,690 TIME TO BE A SEPSIS RESEARCHER 7968 05:00:06,690 --> 05:00:08,859 IS BECAUSE NOT ONLY DO WE HAVE 7969 05:00:08,859 --> 05:00:11,194 ACCESS TO THE COMPUTATIONAL 7970 05:00:11,194 --> 05:00:12,829 RESOURCES TO CAPTURE AND ANALYZE 7971 05:00:12,829 --> 05:00:15,866 A LOT OF THIS DATA, BUT THERE'S 7972 05:00:15,866 --> 05:00:20,370 ALSO -- WE ALSO HAVE THE EAR OF 7973 05:00:20,370 --> 05:00:26,476 A LOT OF INVESTMENT, BOTH 7974 05:00:26,476 --> 05:00:29,313 FINANCIAL AND TIME WISE, IN 7975 05:00:29,313 --> 05:00:30,414 CAPTURING A LOT OF THE KIND OF 7976 05:00:30,414 --> 05:00:33,016 DATA THAT WE WOULD NEED TO HELP 7977 05:00:33,016 --> 05:00:35,085 IDENTIFY EXACTLY WHAT SEPSIS IS 7978 05:00:35,085 --> 05:00:36,720 TO PRATIK'S POINT, AND ALSO HOW 7979 05:00:36,720 --> 05:00:41,124 WE CAN BETTER UNDERSTAND WHAT 7980 05:00:41,124 --> 05:00:42,659 MAY HAPPEN BEFORE IT'S 7981 05:00:42,659 --> 05:00:45,262 CLINICALLY RECOGNIZABLE, AND 7982 05:00:45,262 --> 05:00:46,563 ALSO BREAK DOWN THOSE DIFFERENT 7983 05:00:46,563 --> 05:00:49,633 TYPES OF SEPSIS ONCE IT'S 7984 05:00:49,633 --> 05:00:52,035 IDENTIFIED TO CAPTURE THE 7985 05:00:52,035 --> 05:00:53,470 HETEROGENEITY AND TREATMENT. 7986 05:00:53,470 --> 05:00:56,740 SO I THINK THAT'S ONE THING. 7987 05:00:56,740 --> 05:01:02,112 AND I THINK THERE'S ALSO SOME 7988 05:01:02,112 --> 05:01:03,313 EXAMPLES IN THE CURRENT -- IN 7989 05:01:03,313 --> 05:01:05,248 CURRENT PRACTICE AND ALSO IN 7990 05:01:05,248 --> 05:01:06,049 CERTAIN INSTITUTIONS THAT ARE 7991 05:01:06,049 --> 05:01:09,219 TRYING TO CAPTURE MORE OF THAT 7992 05:01:09,219 --> 05:01:10,087 DATA INDISCRIMINATELY, SO THAT 7993 05:01:10,087 --> 05:01:12,255 PERHAPS WE CAN THEN USE IT LATER 7994 05:01:12,255 --> 05:01:14,458 ON TO ANALYZE AND TO HELP ANSWER 7995 05:01:14,458 --> 05:01:15,993 SOME OF THESE QUESTIONS. 7996 05:01:15,993 --> 05:01:17,628 ONE EXAMPLE THAT I WOULD USE IS 7997 05:01:17,628 --> 05:01:23,433 THE UC SYSTEM, SO THEY CURRENTLY 7998 05:01:23,433 --> 05:01:24,735 HAVE, SPEAKING AS A PERSON WHO'S 7999 05:01:24,735 --> 05:01:26,036 NOT WORKED THERE, SWEEING TO 8000 05:01:26,036 --> 05:01:27,337 SOMEONE WHO BASICALLY KNOWS 8001 05:01:27,337 --> 05:01:30,607 SECONDHAND ABOUT THIS, BUT MY 8002 05:01:30,607 --> 05:01:31,842 UNDERSTANDING IS THEY HAVE THE 8003 05:01:31,842 --> 05:01:34,778 CAPABILITY TO CAPTURE A LOT OF 8004 05:01:34,778 --> 05:01:35,812 THAT DATA AND HAVE INVESTMENT 8005 05:01:35,812 --> 05:01:37,748 AND TRY TO STORE IT AND ANALYZE 8006 05:01:37,748 --> 05:01:39,216 IT FOR THE PURPOSES THAT WE'RE 8007 05:01:39,216 --> 05:01:39,516 DISCUSSING. 8008 05:01:39,516 --> 05:01:42,085 SO I THINK USING THAT AS AN 8009 05:01:42,085 --> 05:01:43,286 EXAMPLE, IF THERE ARE OTHER 8010 05:01:43,286 --> 05:01:44,955 INSTITUTIONS THAT IMPLEMENT 8011 05:01:44,955 --> 05:01:47,457 SIMILAR PROCESSES, AND 8012 05:01:47,457 --> 05:01:48,659 ESSENTIALLY ARE CAPTURING DATA 8013 05:01:48,659 --> 05:01:50,193 THAT WE DON'T REALLY KNOW WHAT 8014 05:01:50,193 --> 05:01:52,262 TO DO YET WITH, I THINK THAT'S 8015 05:01:52,262 --> 05:01:56,199 GOING TO HELP PUSH THE NEEDLE 8016 05:01:56,199 --> 05:01:58,502 AND MOVE THE RESEARCH ALONG TO 8017 05:01:58,502 --> 05:02:04,508 WHERE WE'RE ENVISIONING IT. 8018 05:02:04,508 --> 05:02:06,476 >> GREAT DISCUSSION. 8019 05:02:06,476 --> 05:02:08,779 I DON'T SEE ANYBODY WITH 8020 05:02:08,779 --> 05:02:14,084 QUESTIONS. 8021 05:02:14,084 --> 05:02:15,952 >> I'D LIKE TO MAKE A COMMENT IF 8022 05:02:15,952 --> 05:02:17,087 I MAY FROM THE FUTURE TO 8023 05:02:17,087 --> 05:02:17,854 CURRENT. 8024 05:02:17,854 --> 05:02:20,257 I THINK -- I FEEL OUR BIGGEST 8025 05:02:20,257 --> 05:02:21,358 RESPONSIBILITY AS PHYSICIAN 8026 05:02:21,358 --> 05:02:24,428 SCIENTISTS IS TO AVOID 8027 05:02:24,428 --> 05:02:26,063 SHORTCUTS, TO REALLY DON'T ALLOW 8028 05:02:26,063 --> 05:02:27,798 SHORTCUTS PAUSE THERE ARE NO 8029 05:02:27,798 --> 05:02:31,968 SHORTCUTS HERE. 8030 05:02:31,968 --> 05:02:33,937 DEPLOYING SOMETHING THAT IS 8031 05:02:33,937 --> 05:02:34,638 INADEQUATE, THAT IS LIMITED IS 8032 05:02:34,638 --> 05:02:36,773 NOT GOING TO HELP ANYONE. 8033 05:02:36,773 --> 05:02:37,874 I THINK I'M VERY WORRIED ABOUT 8034 05:02:37,874 --> 05:02:38,842 THAT WITH THE HYPE. 8035 05:02:38,842 --> 05:02:40,877 IF YOU WORKED IN ICU LONG ENOUGH 8036 05:02:40,877 --> 05:02:42,245 AND YOU WORKED WITH THE DATA 8037 05:02:42,245 --> 05:02:44,648 SCIENCE LONG ENOUGH, YOU 8038 05:02:44,648 --> 05:02:45,449 ABSOLUTELY KNOW THAT THE 8039 05:02:45,449 --> 05:02:46,183 SHORTCUTS ARE DANGEROUS. 8040 05:02:46,183 --> 05:02:48,285 AND FOR ME, THAT IS CRITICAL, 8041 05:02:48,285 --> 05:02:50,787 THAT ACTUALLY WE NEED TO STEP UP 8042 05:02:50,787 --> 05:02:52,089 AS A PHYSICIAN AND BECOME A 8043 05:02:52,089 --> 05:02:53,724 GUARDRAIL OF SAFETY OF THIS 8044 05:02:53,724 --> 05:02:55,892 TECHNOLOGY, THAT WILL PENETRATE 8045 05:02:55,892 --> 05:02:57,327 EVERYTHING, AND WE NEED TO 8046 05:02:57,327 --> 05:02:58,895 EDUCATE OUR PHYSICIAN BECAUSE 8047 05:02:58,895 --> 05:03:00,030 EVENTUALLY THERE IS ONLY ONE 8048 05:03:00,030 --> 05:03:01,832 PERSON WHO IS LIABLE, AND THAT'S 8049 05:03:01,832 --> 05:03:03,567 PHYSICIAN. 8050 05:03:03,567 --> 05:03:04,968 SO NO MATTER WHAT TECHNOLOGY 8051 05:03:04,968 --> 05:03:06,403 SAYS, YOU WILL BE SIGNING YOUR 8052 05:03:06,403 --> 05:03:06,770 LIABILITY. 8053 05:03:06,770 --> 05:03:09,039 SO I THINK THAT'S FOR ME A 8054 05:03:09,039 --> 05:03:10,774 REALLY IMPORTANT AND KIND OF 8055 05:03:10,774 --> 05:03:12,109 CAPTURES MY IMAGINATION ON A 8056 05:03:12,109 --> 05:03:14,411 DAILY BASIS. 8057 05:03:14,411 --> 05:03:19,116 >> YOU AGREE, SUCH A GOOD POINT. 8058 05:03:19,116 --> 05:03:20,183 I'M ALSO PUTTING IN A PLUG FOR 8059 05:03:20,183 --> 05:03:23,487 THE NEED FOR -- AND QEN I'M 8060 05:03:23,487 --> 05:03:24,654 TALKING MYSELF OUT OF A JOB HERE 8061 05:03:24,654 --> 05:03:27,290 BUT A NEED FOR DIVERSITY OF 8062 05:03:27,290 --> 05:03:28,158 VOICES. 8063 05:03:28,158 --> 05:03:31,695 I THINK FOR TOO LONG, SEPSIS HAS 8064 05:03:31,695 --> 05:03:33,196 FALLEN IN THE DOMAIN OF CRITICAL 8065 05:03:33,196 --> 05:03:33,530 CARE. 8066 05:03:33,530 --> 05:03:35,732 BY THE TIME THEY GET THERE, IT'S 8067 05:03:35,732 --> 05:03:36,700 PROBABLY -- IT'S KIND OF TOO 8068 05:03:36,700 --> 05:03:38,468 LATE, AND YOU GET INTO THIS 8069 05:03:38,468 --> 05:03:40,537 BOTTLENECK OF PATHOPHYSIOLOGICAL 8070 05:03:40,537 --> 05:03:42,072 PATHWAYS THAT ARE CLOSER TO 8071 05:03:42,072 --> 05:03:44,341 DEATH THAN THEY ARE TO THE HOST 8072 05:03:44,341 --> 05:03:47,310 TRYING TO MAKE THEMSELVES 8073 05:03:47,310 --> 05:03:47,644 BETTER. 8074 05:03:47,644 --> 05:03:49,980 AND THAT WE NEED TO DIVERSIFY 8075 05:03:49,980 --> 05:03:51,348 WHERE WE'RE DOING THESE STUDIES 8076 05:03:51,348 --> 05:03:52,749 AND I THINK AS WE'RE TOUCHED 8077 05:03:52,749 --> 05:03:55,218 UPON IT TOO, MY THING IS, YOU 8078 05:03:55,218 --> 05:03:56,486 KNOW, HOW MUCH OF THIS IS 8079 05:03:56,486 --> 05:03:58,655 ACTUALLY PREVENTABLE? 8080 05:03:58,655 --> 05:04:00,423 AND YOU KNOW, I REALLY WANT TO 8081 05:04:00,423 --> 05:04:02,292 FOCUS GOING FUTURE -- GOING INTO 8082 05:04:02,292 --> 05:04:05,362 THE FUTURE AND TO ANDRE'S POINT, 8083 05:04:05,362 --> 05:04:06,763 WE NEED TO COLLECT DATA THAT WE 8084 05:04:06,763 --> 05:04:08,198 DON'T KNOW WE NEED, AND WE NEED 8085 05:04:08,198 --> 05:04:10,233 TO COLLECT IT INDISCRIMINATELY, 8086 05:04:10,233 --> 05:04:10,934 AND THINK IT IS HAPPENING MORE 8087 05:04:10,934 --> 05:04:11,368 AND MORE. 8088 05:04:11,368 --> 05:04:15,639 SO ANOTHER PLUG FOR OUR APS 8089 05:04:15,639 --> 05:04:17,274 CONSORTIUM, WHICH IS SPONSORED 8090 05:04:17,274 --> 05:04:20,777 BY THE NHLBI AND N IGMS. 8091 05:04:20,777 --> 05:04:22,979 WE ARE ACTUALLY COLLECTING 8092 05:04:22,979 --> 05:04:24,047 MULTIDIMENSIONAL CLINICAL AND 8093 05:04:24,047 --> 05:04:25,248 BIOLOGICAL DATA AND THAT 8094 05:04:25,248 --> 05:04:28,018 RESOURCE IS AVAILABLE FOR 8095 05:04:28,018 --> 05:04:28,585 EVERYBODY. 8096 05:04:28,585 --> 05:04:30,187 SO PLEASE REACH OUT AND TAP INTO 8097 05:04:30,187 --> 05:04:34,791 THAT FOR YOUR RESEARCH PROGRAMS. 8098 05:04:34,791 --> 05:04:36,126 >> IT'S IMPORTANT ALSO, THAT'S A 8099 05:04:36,126 --> 05:04:37,828 VERY GOOD POINT ABOUT 8100 05:04:37,828 --> 05:04:38,628 DIVERSIFYING THE SETTINGS. 8101 05:04:38,628 --> 05:04:41,131 I'M A PEDIATRIC ER DOC, AND WE 8102 05:04:41,131 --> 05:04:42,999 NEED TO UTILIZE THE EMERGENCY 8103 05:04:42,999 --> 05:04:43,967 ROOM. 8104 05:04:43,967 --> 05:04:45,168 THAT'S WHERE THE PATIENT SHOWS 8105 05:04:45,168 --> 05:04:46,937 UP, YOU KNOW, BEFORE THEY GET TO 8106 05:04:46,937 --> 05:04:49,873 THE ICU OR TO THE FLOOR, SO 8107 05:04:49,873 --> 05:04:52,609 THERE'S A LOT TO BE DONE THERE. 8108 05:04:52,609 --> 05:04:53,376 UNFORTUNATELY ONE OF THE MAJOR 8109 05:04:53,376 --> 05:04:54,578 PROBLEMS AND I'M GOING BACK TO 8110 05:04:54,578 --> 05:04:56,546 THE DEFINITIONS IS THAT THE 8111 05:04:56,546 --> 05:04:58,415 DEFINITIONS ARE MOSTLY FOR THE 8112 05:04:58,415 --> 05:05:00,817 ICU BECAUSE EVEN SEPSIS 3, WE 8113 05:05:00,817 --> 05:05:03,220 DON'T HAVE ALL THAT DATA IN THE 8114 05:05:03,220 --> 05:05:05,188 FIRST HOUR OR TWO IN THE 8115 05:05:05,188 --> 05:05:06,389 EMERGENCY ROOM, SO THAT BECOMES 8116 05:05:06,389 --> 05:05:13,964 A HUGE PROBLEM. 8117 05:05:13,964 --> 05:05:15,465 >> EXCELLENT POINT. 8118 05:05:15,465 --> 05:05:17,200 PRATIK, I LIKE TO USE THE SLIDE 8119 05:05:17,200 --> 05:05:19,402 WHERE I SAY THE ICU IS AN EXIT 8120 05:05:19,402 --> 05:05:19,636 WOUND. 8121 05:05:19,636 --> 05:05:22,038 LIKE YOU CAN PATCH UP AN EXIT 8122 05:05:22,038 --> 05:05:23,440 WOUND BUT BY THE TIME YOU'RE 8123 05:05:23,440 --> 05:05:25,442 THERE, IT'S A BYPRODUCT OF A 8124 05:05:25,442 --> 05:05:27,277 BULLET THAT'S GONE THROUGH AND 8125 05:05:27,277 --> 05:05:28,712 CREATED ITS OWN KIND OF 8126 05:05:28,712 --> 05:05:30,780 WHATEVER, YOU KNOW, TRAJECTORY. 8127 05:05:30,780 --> 05:05:34,084 WE HAVE TO GET TO PROJECTILE 8128 05:05:34,084 --> 05:05:36,586 ITSELF AND TO THE GUN OR 8129 05:05:36,586 --> 05:05:37,587 WHATEVER. 8130 05:05:37,587 --> 05:05:38,822 AND SO WE DO NEED TO INCLUDE 8131 05:05:38,822 --> 05:05:40,523 THOSE VOICES. 8132 05:05:40,523 --> 05:05:41,858 ABSOLUTELY. 8133 05:05:41,858 --> 05:05:52,402 IT LOOKS LIKE NITIN, YOU HAVE A 8134 05:05:53,203 --> 05:05:53,403 QUESTION. 8135 05:05:53,403 --> 05:05:55,071 >> THIS IS A VERY INTRIGUING 8136 05:05:55,071 --> 05:05:56,506 DISCUSSION, ESPECIALLY WHAT 8137 05:05:56,506 --> 05:05:59,809 PRATIK SAID, HE STILL KIND OF 8138 05:05:59,809 --> 05:06:02,846 TRIES TO UNDERSTAND WHAT SEPSIS 8139 05:06:02,846 --> 05:06:03,280 IS. 8140 05:06:03,280 --> 05:06:05,048 YOU DID SHARE SOME PARTS ABOUT 8141 05:06:05,048 --> 05:06:07,984 WHY YOU THINK SO. 8142 05:06:07,984 --> 05:06:09,419 BUT MY QUESTION WAS THAT IF -- 8143 05:06:09,419 --> 05:06:10,420 AND THIS QUESTION IS FOR 8144 05:06:10,420 --> 05:06:12,155 EVERYBODY HERE ON THE PANEL OR 8145 05:06:12,155 --> 05:06:14,858 IN THE WHOLE MEETING, THAT IF 8146 05:06:14,858 --> 05:06:16,760 YOU HAVE TO DEFINE CERTAIN 8147 05:06:16,760 --> 05:06:20,363 PARAMETERS THAT SHOULD BE THE 8148 05:06:20,363 --> 05:06:25,068 PATHWAY TO IDENTIFY SEPSIS, THEN 8149 05:06:25,068 --> 05:06:26,169 WHAT WOULD THEY BE? 8150 05:06:26,169 --> 05:06:27,270 BECAUSE RIGHT NOW WE HAVE 8151 05:06:27,270 --> 05:06:28,672 IDENTIFIED A CRITICAL GAP IN THE 8152 05:06:28,672 --> 05:06:31,541 KNOWLEDGE BASICALLY THAT IT'S 8153 05:06:31,541 --> 05:06:36,880 NOT WELL-DEFINED WHAT MEANS -- 8154 05:06:36,880 --> 05:06:37,847 WHAT SEPSIS MEANS AT THAT END. 8155 05:06:37,847 --> 05:06:39,616 SO HOW SHOULD IT BE DEFINED IN 8156 05:06:39,616 --> 05:06:48,091 YOUR VIEW? 8157 05:06:48,091 --> 05:06:49,459 >> I HAVE TO LEAVE, I'M AFRAID. 8158 05:06:49,459 --> 05:06:50,560 I CAN'T ANSWER THAT QUESTION. 8159 05:06:50,560 --> 05:06:58,735 IT'S TOO HARD. 8160 05:06:58,735 --> 05:07:00,403 AGAIN I'M JUST GOING TO GIVE A 8161 05:07:00,403 --> 05:07:00,971 VERY SHORT ANSWER. 8162 05:07:00,971 --> 05:07:02,939 I THINK THERE ARE PRACTICAL 8163 05:07:02,939 --> 05:07:04,140 UTILITIES OF HOW WE'VE BEEN 8164 05:07:04,140 --> 05:07:06,576 DOING SEPSIS SO FAR. 8165 05:07:06,576 --> 05:07:09,846 I THINK IT HAS FOCUSED THE MIND 8166 05:07:09,846 --> 05:07:12,349 TOWARDS EARLY ANTIBIOTICS, 8167 05:07:12,349 --> 05:07:15,652 RESUSCITATION OF PATIENTS WHO 8168 05:07:15,652 --> 05:07:17,287 ARE DEMONSTRATING EARLY SIGNS OF 8169 05:07:17,287 --> 05:07:18,254 ORGAN FAILURE. 8170 05:07:18,254 --> 05:07:22,225 BUT BEYOND THAT, IT IS REALLY, 8171 05:07:22,225 --> 05:07:25,395 REALLY DIFFICULT TO FIND 8172 05:07:25,395 --> 05:07:26,896 FEATURES THAT WOULD EXIST IN 8173 05:07:26,896 --> 05:07:31,401 THIS IDEAL MODEL BECAUSE 8174 05:07:31,401 --> 05:07:32,936 INFECTIOUS RESPONSES ARE SO 8175 05:07:32,936 --> 05:07:34,904 VARIED, THEY ARE SO DYNAMIC, 8176 05:07:34,904 --> 05:07:38,508 THAT I THINK WE NEED TO START 8177 05:07:38,508 --> 05:07:39,743 FROM THE BEGINNING AND WE NEED 8178 05:07:39,743 --> 05:07:45,615 TO COLLECT DATA AND UNDERSTAND 8179 05:07:45,615 --> 05:07:47,617 EXACTLY WHAT IT IS AND WHAT ARE 8180 05:07:47,617 --> 05:07:51,554 THE FACTORS THAT DRIVE THE HOST 8181 05:07:51,554 --> 05:07:53,189 RESPONSE. 8182 05:07:53,189 --> 05:07:57,360 WE HAVE SOME VERY EARLY TA THAT 8183 05:07:57,360 --> 05:07:59,763 SUGGESTS EVEN IN BACTERIAL 8184 05:07:59,763 --> 05:08:00,864 INFECTIONS, THE PATHOGEN 8185 05:08:00,864 --> 05:08:02,132 SPECIFIC RESPONSE OF THE HOST IS 8186 05:08:02,132 --> 05:08:02,499 QUITE DIFFERENT. 8187 05:08:02,499 --> 05:08:03,933 THESE ARE SORT OF FOUNDATIONAL 8188 05:08:03,933 --> 05:08:05,035 PRINCIPLES THAT WE HAVE NOT GOT 8189 05:08:05,035 --> 05:08:05,468 AT. 8190 05:08:05,468 --> 05:08:07,337 SO I THINK EVEN BEFORE WE CAN 8191 05:08:07,337 --> 05:08:11,174 GET TO THESE FEATURES THAT COULD 8192 05:08:11,174 --> 05:08:13,877 UNIFY THIS SORT OF DISEASE 8193 05:08:13,877 --> 05:08:15,879 STATE, WE NEED TO BETTER DEFINE 8194 05:08:15,879 --> 05:08:17,313 WHAT IT IS, WHAT DRIVES IT. 8195 05:08:17,313 --> 05:08:21,017 >> I JUST -- WE'VE SPENT ENDLESS 8196 05:08:21,017 --> 05:08:22,652 AMOUNT OF TIME TRYING TO FIGURE 8197 05:08:22,652 --> 05:08:23,753 OUT WHAT OUR ELECTRONIC 8198 05:08:23,753 --> 05:08:24,921 DEFINITION WOULD BE, RECOGNIZING 8199 05:08:24,921 --> 05:08:26,289 THAT ALL OF THEM WOULD BE 8200 05:08:26,289 --> 05:08:27,690 IMPERFECT, AND I FEEL LIKE 8201 05:08:27,690 --> 05:08:31,761 THERE'S A RELIANCE ON OUR 8202 05:08:31,761 --> 05:08:33,063 IMMUNOLOGIC COLLEAGUES DOING 8203 05:08:33,063 --> 05:08:34,931 BASIC SCIENCE RESEARCH TO 8204 05:08:34,931 --> 05:08:38,101 ACTUALLY FIGURE OUT WHAT THE 8205 05:08:38,101 --> 05:08:39,436 PATHOPHYSIOLOGY IS TO TEST THAT 8206 05:08:39,436 --> 05:08:41,738 WE CAN THEN BUILD OUT CLINICALLY 8207 05:08:41,738 --> 05:08:43,506 AND INCORPORATE INTO OUR MODELS 8208 05:08:43,506 --> 05:08:45,041 BUT UNTIL IT EXISTS WE'RE USING 8209 05:08:45,041 --> 05:08:47,544 ALL OF THESE ROUGH PARAMETERS. 8210 05:08:47,544 --> 05:08:49,179 I LIKE TO USE THE ANALOGY, I 8211 05:08:49,179 --> 05:08:50,513 DON'T KNOW IF YOU'VE HEARD THAT 8212 05:08:50,513 --> 05:08:51,314 QUOTE FROM THE SUPREME COURT, 8213 05:08:51,314 --> 05:08:54,117 THAT THEY DIDN'T KNOW WHAT 8214 05:08:54,117 --> 05:08:55,685 PORNOGRAPHY WAS, THEY KNOW IT 8215 05:08:55,685 --> 05:08:57,420 WHEN THEY SEE IT, AND I FEEL THE 8216 05:08:57,420 --> 05:08:58,822 SAME WAY AS A CLINICIAN, IT 8217 05:08:58,822 --> 05:09:00,123 LIKE, I CAN'T DEFINE SEPSIS BUT 8218 05:09:00,123 --> 05:09:01,691 I KNOW IT WHEN I SEE IT. 8219 05:09:01,691 --> 05:09:03,226 BUT HOW DO YOU ACTUALLY, LIKE, 8220 05:09:03,226 --> 05:09:06,196 MAKE THAT A PREDICTABLE OUTCOME? 8221 05:09:06,196 --> 05:09:08,264 OBVIOUSLY THE CLINICIAN GESTALT 8222 05:09:08,264 --> 05:09:10,233 JUST IMPOSSIBLE TO CAPTURE IN 8223 05:09:10,233 --> 05:09:11,034 STRUCTURED DATA. 8224 05:09:11,034 --> 05:09:12,001 WHICH IS WHY I DO THINK THERE'S 8225 05:09:12,001 --> 05:09:13,536 A LOT OF OPPORTUNITY IN THIS 8226 05:09:13,536 --> 05:09:14,971 UNSTRUCTURED DATA, BUT IT'S 8227 05:09:14,971 --> 05:09:16,840 STILL NOT THE KEY 8228 05:09:16,840 --> 05:09:18,575 PATHOPHYSIOLOGY OF WHAT'S GOING 8229 05:09:18,575 --> 05:09:19,876 WRONG WITH THE IMMUNE RESPONSE 8230 05:09:19,876 --> 05:09:21,878 THAT WE NEED OUR BASIC SCIENCE 8231 05:09:21,878 --> 05:09:24,280 RESEARCHERS TO ANSWER FOR US. 8232 05:09:24,280 --> 05:09:26,249 >> AND MAYBE JUST TO EXPAND, IF 8233 05:09:26,249 --> 05:09:27,951 YOU DON'T MIND, CARA, IS LIKE, 8234 05:09:27,951 --> 05:09:30,653 YOU KNOW, THE WAY HOW I ALSO 8235 05:09:30,653 --> 05:09:32,489 THINK ABOUT IT AS A MENTAL MODEL 8236 05:09:32,489 --> 05:09:35,358 IS THAT FOR ME, SEPSIS IS JUST 8237 05:09:35,358 --> 05:09:37,327 ANOTHER MANIFESTATION OF, YOU 8238 05:09:37,327 --> 05:09:40,063 KNOW, AGING HUMAN BODY IN 8239 05:09:40,063 --> 05:09:41,264 CONTACT WITH THE ENVIRONMENT. 8240 05:09:41,264 --> 05:09:42,732 LIKE WE ARE CONSTANTLY BATTLING 8241 05:09:42,732 --> 05:09:43,233 THE WORLD. 8242 05:09:43,233 --> 05:09:46,503 AND YOU KNOW, THE INFECTION IS 8243 05:09:46,503 --> 05:09:48,338 JUST ONE THING THAT CAN KILL US. 8244 05:09:48,338 --> 05:09:49,939 THERE'S INJURY, THERE'S TRAUMA, 8245 05:09:49,939 --> 05:09:51,207 ALL KIND OF STUFF. 8246 05:09:51,207 --> 05:09:55,712 SURGERY, CANCER. 8247 05:09:55,712 --> 05:09:57,147 BUT IT IS A VERY HOLISTIC 8248 05:09:57,147 --> 05:09:58,248 PROCESS. 8249 05:09:58,248 --> 05:09:59,682 I WOULD SAY IT'S A CONTROL 8250 05:09:59,682 --> 05:10:00,650 SYSTEM PROBLEM, IT A PROBLEM 8251 05:10:00,650 --> 05:10:04,921 WITH THE CONTROL, SO IT IT AFFES 8252 05:10:04,921 --> 05:10:05,688 EVERY SINGLE ORGAN. 8253 05:10:05,688 --> 05:10:07,790 WE CALL IT HOMEOSTASIS. 8254 05:10:07,790 --> 05:10:08,958 WE STILL DON'T UNDERSTAND 8255 05:10:08,958 --> 05:10:10,193 COMPLETELY HOW IT HAPPENS, HOW 8256 05:10:10,193 --> 05:10:12,495 WE AGE, AND GETTING DEEPER 8257 05:10:12,495 --> 05:10:14,030 UNDERSTANDING OF HUMAN HEALTH 8258 05:10:14,030 --> 05:10:16,332 WOULD HELP US ALSO DEFINE ALL OF 8259 05:10:16,332 --> 05:10:17,534 THESE VERY COMPLEX PRACTICES 8260 05:10:17,534 --> 05:10:19,068 THAT HAPPENS WITH AGING. 8261 05:10:19,068 --> 05:10:22,605 THAT'S WHY YOU SEE 8262 05:10:22,605 --> 05:10:23,673 COMORBIDITIES, ELDERLY, WHEN YOU 8263 05:10:23,673 --> 05:10:25,108 ADD ADDITIONAL INSULTS, IT 8264 05:10:25,108 --> 05:10:26,442 BECOMES REALLY HARRER. 8265 05:10:26,442 --> 05:10:28,178 AND I THINK AS MUCH AS I WANT US 8266 05:10:28,178 --> 05:10:29,479 TO BE OUTSIDE OF THE WORK, I 8267 05:10:29,479 --> 05:10:34,517 WOULD SAY WE CAN PROBABLY LEARN 8268 05:10:34,517 --> 05:10:36,719 HOW TO TAKE CARE OF A LOT OF 8269 05:10:36,719 --> 05:10:38,922 THESE THINGS SO THEY DON'T LAP 8270 05:10:38,922 --> 05:10:45,728 BUT THERE WILL ALSO BE VERY 8271 05:10:45,728 --> 05:10:46,930 OLDER PEOPLE THAT WE WILL HAVE 8272 05:10:46,930 --> 05:10:48,765 TO DEAL WITH, AND AT THAT POINT 8273 05:10:48,765 --> 05:10:50,200 WE NEED TO UNDERSTAND WHAT DOES 8274 05:10:50,200 --> 05:10:51,434 IT NEED TO CONTROL IN THE BODY 8275 05:10:51,434 --> 05:10:54,504 LIKE WHAT AND HOW DO WE -- I 8276 05:10:54,504 --> 05:10:56,839 DON'T KNOW WHAT, BUT IT WILL 8277 05:10:56,839 --> 05:10:58,374 COME, NOT MAYBE IN MY LIFETIME, 8278 05:10:58,374 --> 05:11:01,010 BUT I HOPE IT IS MAYBE BECAUSE I 8279 05:11:01,010 --> 05:11:02,545 PLAN TO LIVE 150 YEARS SO WE 8280 05:11:02,545 --> 05:11:06,115 WILL SEE. 8281 05:11:06,115 --> 05:11:08,184 >> I THINK PART OF IT ALSO IS 8282 05:11:08,184 --> 05:11:09,252 NUMBER ONE, THERE'S THIS 8283 05:11:09,252 --> 05:11:10,653 DISCONNECT BETWEEN THE DATA 8284 05:11:10,653 --> 05:11:11,754 CLINICIANS HAVE ACCESS TO AND 8285 05:11:11,754 --> 05:11:13,189 WHAT WE POTENTIALLY COULD BE 8286 05:11:13,189 --> 05:11:13,723 TESTING. 8287 05:11:13,723 --> 05:11:15,291 SO A LOT OF THAT ISN'T AT THE 8288 05:11:15,291 --> 05:11:15,525 BEDSIDE. 8289 05:11:15,525 --> 05:11:17,126 I THINK IF WE GET TO THAT POINT 8290 05:11:17,126 --> 05:11:18,561 WHERE WE CAN HAVE A LOT OF THAT 8291 05:11:18,561 --> 05:11:20,163 DATA AVAILABLE TO US, MAYBE IT 8292 05:11:20,163 --> 05:11:24,367 MIGHT BE EASIER FOR US TO 8293 05:11:24,367 --> 05:11:26,369 IDENTIFY EXACTLY WHAT SEPSIS IS. 8294 05:11:26,369 --> 05:11:27,904 THE OTHER THING -- THE OTHER 8295 05:11:27,904 --> 05:11:29,839 DATA THAT WE'RE MISSING TO 8296 05:11:29,839 --> 05:11:30,440 AZRA'S POINT BEFORE IS THAT I 8297 05:11:30,440 --> 05:11:32,075 HAVE NO IDEA AT WHAT STAGE THIS 8298 05:11:32,075 --> 05:11:34,544 PATIENT IS COMING TO ME IN THEIR 8299 05:11:34,544 --> 05:11:35,578 SEPSIS. 8300 05:11:35,578 --> 05:11:37,347 SO PATIENTS THAT I SEE IN MY 8301 05:11:37,347 --> 05:11:38,314 HOSPITAL, FOR INSTANCE, TEND TO 8302 05:11:38,314 --> 05:11:40,516 COME PRETTY LATE. 8303 05:11:40,516 --> 05:11:41,618 WHEN THEY'VE ALREADY EXHIBITED 8304 05:11:41,618 --> 05:11:43,586 LOTS OF SIGNS OF ORGAN 8305 05:11:43,586 --> 05:11:44,020 DYSFUNCTION. 8306 05:11:44,020 --> 05:11:45,788 BUT THERE ARE PATIENTS IN OTHER 8307 05:11:45,788 --> 05:11:46,956 HOSPITALS WHO MAY COME VERY 8308 05:11:46,956 --> 05:11:50,393 EARLY IN THEIR CLINICAL CORKS CE 8309 05:11:50,393 --> 05:11:51,794 AND THOSE TWO DISEASE STATES AT 8310 05:11:51,794 --> 05:11:53,029 THAT PARTICULAR TIME MAY BE VERY 8311 05:11:53,029 --> 05:11:54,264 DIFFERENT IN TERMS OF THEIR HOST 8312 05:11:54,264 --> 05:11:54,998 RESPONSE. 8313 05:11:54,998 --> 05:11:56,733 SO I CAN'T REALLY QUANTIFY 8314 05:11:56,733 --> 05:11:57,834 EXACTLY WHAT THAT LOOKS LIKE 8315 05:11:57,834 --> 05:11:59,402 WITHOUT KNOWING WHAT THEIR 8316 05:11:59,402 --> 05:12:03,206 BASELINE DATA IS. 8317 05:12:03,206 --> 05:12:04,841 SO ACCESS TO THAT KIND OF DATA I 8318 05:12:04,841 --> 05:12:07,176 THINK WOULD ALSO INFORM HOW WE 8319 05:12:07,176 --> 05:12:11,781 DEFINE SEPSIS IN THE FUTURE. 8320 05:12:11,781 --> 05:12:13,182 >> I READ A BOOK ABOUT 8321 05:12:13,182 --> 05:12:14,117 HURRICANES AND THE TECHNOLOGY 8322 05:12:14,117 --> 05:12:16,252 THEY USED OVER TIME TO IMPROVE 8323 05:12:16,252 --> 05:12:20,356 OUR FORECASTING AND NOT 8324 05:12:20,356 --> 05:12:21,190 TREATMENT BUT WHATEVER THEY 8325 05:12:21,190 --> 05:12:22,592 COULD DO TO MINIMIZE THE 8326 05:12:22,592 --> 05:12:28,231 BYPRODUCTS OF THAT, AND I THINK 8327 05:12:28,231 --> 05:12:31,634 OUR -- ARE SOMEWHERE LIKE THE 8328 05:12:31,634 --> 05:12:36,339 WIND SPEED, BUT THEY'RE VERY 8329 05:12:36,339 --> 05:12:36,639 INCOMPLETE. 8330 05:12:36,639 --> 05:12:38,174 I THINK A LOT OF THAT HISTORY 8331 05:12:38,174 --> 05:12:41,377 STARTED WITH THE MODELING 8332 05:12:41,377 --> 05:12:42,178 APPROACHES, TRAJECTORIES THAT 8333 05:12:42,178 --> 05:12:44,113 CAN START FROM THE VERY INITIAL 8334 05:12:44,113 --> 05:12:46,282 STAGE, LIKE AZRA HAS DESCRIBED, 8335 05:12:46,282 --> 05:12:49,452 WE'RE CONSTANTLY BEING INSULTED, 8336 05:12:49,452 --> 05:12:50,420 FOR SOME REASON AT TIMES WE CAN 8337 05:12:50,420 --> 05:12:51,688 PUT THAT DOWN AND AT OTHER TIMES 8338 05:12:51,688 --> 05:12:54,657 IT BECOMES THIS RAGING 8339 05:12:54,657 --> 05:12:55,191 HURRICANE. 8340 05:12:55,191 --> 05:12:56,626 BUT THEN INSTRUMENTING THAT 8341 05:12:56,626 --> 05:12:57,527 PROCESS OVER TIME, THEY USED TO 8342 05:12:57,527 --> 05:12:59,162 FLY AIRPLANES REALLY CLOSE OR IN 8343 05:12:59,162 --> 05:13:00,229 AND NOW THEY HAVE ALL THESE 8344 05:13:00,229 --> 05:13:02,131 ACCEPT SORES WHICH THEY CAN 8345 05:13:02,131 --> 05:13:05,601 DEPLOY, ACTUALLY DIRECTLY INTO 8346 05:13:05,601 --> 05:13:08,371 THAT HURRICANE. 8347 05:13:08,371 --> 05:13:09,939 SO THINKING -- BUT THE TAXONOMY 8348 05:13:09,939 --> 05:13:11,107 OF IT ALL WAS VERY, VERY 8349 05:13:11,107 --> 05:13:12,408 IMPORTANT TO DRIVE KIND OF THE 8350 05:13:12,408 --> 05:13:15,478 UNDERSTANDING OF HOW TO MITIGATE 8351 05:13:15,478 --> 05:13:16,446 THE BYPRODUCTS. 8352 05:13:16,446 --> 05:13:19,982 IT LOOKS LIKE WE HAD SOME OTHER 8353 05:13:19,982 --> 05:13:20,416 HANDS. 8354 05:13:20,416 --> 05:13:22,385 LET'S START WITH DR. LIAW 8355 05:13:22,385 --> 05:13:23,353 BECAUSE THE OTHERS HAVE 8356 05:13:23,353 --> 05:13:27,256 RETRACTED THEIR HANDS FOR NOW. 8357 05:13:27,256 --> 05:13:27,990 >> HI. 8358 05:13:27,990 --> 05:13:30,927 I WAS JUST WONDERING, IN THE 8359 05:13:30,927 --> 05:13:35,665 U.S., IS THERE A NETWORK FOR 8360 05:13:35,665 --> 05:13:35,898 SEPSIS? 8361 05:13:35,898 --> 05:13:37,100 I'M JUST THINKING IN CANADA, WE 8362 05:13:37,100 --> 05:13:38,935 HAVE SEPSIS CANADA, WHICH IS A 8363 05:13:38,935 --> 05:13:40,803 RESEARCH NETWORK MADE UP OF 8364 05:13:40,803 --> 05:13:41,604 RESEARCHERS, HEALTHCARE 8365 05:13:41,604 --> 05:13:47,043 PROVIDERS AND PATIENT PARTNERS, 8366 05:13:47,043 --> 05:13:48,277 AND WE HAVE SEVERAL GOALS THAT 8367 05:13:48,277 --> 05:13:50,913 RANGE FROM BASIC RESEARCH TO 8368 05:13:50,913 --> 05:13:51,681 POPULATION STUDIES. 8369 05:13:51,681 --> 05:13:53,449 I'M JUST WONDERING, IS THAT 8370 05:13:53,449 --> 05:13:54,784 SOMETHING THAT'S ALSO PRESENT IN 8371 05:13:54,784 --> 05:14:00,490 THE U.S.? 8372 05:14:00,490 --> 05:14:01,758 >> THERE ARE MULTIPLE NETWORKS. 8373 05:14:01,758 --> 05:14:03,826 I CAN TALK ABOUT PEDIATRIC 8374 05:14:03,826 --> 05:14:06,462 NETWORKS. 8375 05:14:06,462 --> 05:14:07,930 STUDY FOR KRIN CAL CARE 8376 05:14:07,930 --> 05:14:11,167 MEDICINE, THE P CARD, ACTUALLY 8377 05:14:11,167 --> 05:14:12,168 AN ASSOCIATION OF EMERGENCY 8378 05:14:12,168 --> 05:14:14,871 DEPARTMENTS ACROSS THE U.S. 8379 05:14:14,871 --> 05:14:17,874 AND THERE IS CRITICAL CARE, 8380 05:14:17,874 --> 05:14:20,576 SEVERE ILLNESS AND TRAUMA 8381 05:14:20,576 --> 05:14:21,677 SUBGROUP THIS WORKS ON SEPSIS. 8382 05:14:21,677 --> 05:14:25,648 SO THERE ARE MULTIPLE DIFFERENT 8383 05:14:25,648 --> 05:14:26,949 ORGANIZATIONS AND CONSORTIA THAT 8384 05:14:26,949 --> 05:14:29,252 WILL WORK ON SEPSIS IN THE U.S. 8385 05:14:29,252 --> 05:14:31,020 AGAIN, I KNOW MORE ABOUT THE 8386 05:14:31,020 --> 05:14:33,990 PEDIATRIC WORLD, BUT MANY OF YOU 8387 05:14:33,990 --> 05:14:35,191 KNOW ABOUT THE ADULT WORLD AS 8388 05:14:35,191 --> 05:14:35,391 WELL. 8389 05:14:35,391 --> 05:14:41,864 >> OKAY, THANK YOU. 8390 05:14:41,864 --> 05:14:46,436 >> I SAW HANDS UP BEFORE, DID 8391 05:14:46,436 --> 05:14:48,070 YOU WANT TO COME BACK ON AND ASK 8392 05:14:48,070 --> 05:14:50,540 YOUR QUESTION? 8393 05:14:50,540 --> 05:14:55,812 >> GUOFEI I AM ASSUMING THAT 8394 05:14:55,812 --> 05:14:57,146 MOST HOSPITALS HAVE THE DATA FOR 8395 05:14:57,146 --> 05:15:02,485 PATIENTS WHO DIED OF SEPSIS, 8396 05:15:02,485 --> 05:15:04,687 WHICH WERE SEVERE SEPSIS. 8397 05:15:04,687 --> 05:15:08,191 IS IT POSSIBLE OR MAYBE YOU 8398 05:15:08,191 --> 05:15:09,592 ALREADY HAVE THE -- THAT THESE 8399 05:15:09,592 --> 05:15:11,360 A.I. ALGORITHMS, YOU CAN TRAIN 8400 05:15:11,360 --> 05:15:15,698 THEM, FOR ALL THOSE PATIENTS AND 8401 05:15:15,698 --> 05:15:18,067 BASED ON THEIR EMR DATA PO 8402 05:15:18,067 --> 05:15:21,337 PREDICT MORTALITY OR SEVERITY OF 8403 05:15:21,337 --> 05:15:23,439 SEPSIS RATHER THAN DIFFERENT 8404 05:15:23,439 --> 05:15:24,407 STAGES OR TREATMENT THAT SOME 8405 05:15:24,407 --> 05:15:25,875 PATIENT WHETHER IT'S A 8406 05:15:25,875 --> 05:15:26,809 TRAJECTORY TOWARDS MORTALITY OR 8407 05:15:26,809 --> 05:15:30,346 NOT. 8408 05:15:30,346 --> 05:15:32,982 >> GO AHEAD, ANDRE. 8409 05:15:32,982 --> 05:15:34,417 >> WELL, I WAS JUST GOING TO 8410 05:15:34,417 --> 05:15:36,152 SAY, SO THERE ARE -- AS A MATTER 8411 05:15:36,152 --> 05:15:37,820 OF FACT, IN THE EARLIER STAGES 8412 05:15:37,820 --> 05:15:38,821 OF THIS RESEARCH, THERE WERE A 8413 05:15:38,821 --> 05:15:40,323 LOT OF MODELS THAT PREDICTED 8414 05:15:40,323 --> 05:15:41,858 MORTALITY IN PATIENTS WITH 8415 05:15:41,858 --> 05:15:42,825 SEPSIS. 8416 05:15:42,825 --> 05:15:44,427 THE PROBLEM WITH PREDICTING 8417 05:15:44,427 --> 05:15:45,695 MORTALITY IS AS A CLINICIAN, I 8418 05:15:45,695 --> 05:15:47,029 HAVE NO IDEA WHAT TO DO WITH 8419 05:15:47,029 --> 05:15:49,532 THAT INFORMATION. 8420 05:15:49,532 --> 05:15:51,000 SO WHAT IS THE ACTIONABLE THING 8421 05:15:51,000 --> 05:15:52,635 THAT I CAN DO THAT I CAN PREVENT 8422 05:15:52,635 --> 05:15:56,239 THAT FROM HAPPENING? 8423 05:15:56,239 --> 05:15:59,041 AND SO THAT'S PARTLY WHY A LOT 8424 05:15:59,041 --> 05:16:00,977 OF IT, THE WORK THAT'S HAPPENED 8425 05:16:00,977 --> 05:16:04,814 SINCE THEN, IS STO HELP IDENTIFY 8426 05:16:04,814 --> 05:16:07,650 THINGS THAT WE CAN ACTUALLY FIND 8427 05:16:07,650 --> 05:16:10,086 SOMETHING THAT THAT OUTCOME IS 8428 05:16:10,086 --> 05:16:15,124 ASSOCIATED WITH, AND LINK IT 8429 05:16:15,124 --> 05:16:16,092 BACK TO SOMETHING THAT I CAN DO 8430 05:16:16,092 --> 05:16:18,561 TO CORRECT IT. 8431 05:16:18,561 --> 05:16:20,530 >> GREAT. 8432 05:16:20,530 --> 05:16:22,632 AND GUOFEI, FINAL QUESTION? 8433 05:16:22,632 --> 05:16:24,367 >> SURE, THANK YOU, VINNY. 8434 05:16:24,367 --> 05:16:27,436 SO REGARDING THE DIFFERENT 8435 05:16:27,436 --> 05:16:31,073 VOICES, SO YOU GUYS WANT THE 8436 05:16:31,073 --> 05:16:33,876 MULTIPLICITY OF DATA IN SAMPLING 8437 05:16:33,876 --> 05:16:34,477 OF BIOMARKERS. 8438 05:16:34,477 --> 05:16:36,579 I DID NOT HEAR YOU GUYS TOUCHING 8439 05:16:36,579 --> 05:16:39,015 UPON THE PATIENT ANGLE, HOW THE 8440 05:16:39,015 --> 05:16:40,917 PATIENT THINKS AND HOW DOES 8441 05:16:40,917 --> 05:16:41,984 PATIENT PERSPECTIVE CONTRIBUTE 8442 05:16:41,984 --> 05:16:44,287 TO THE A.I. MODELS YOU GUYS 8443 05:16:44,287 --> 05:16:48,324 BUILD UPON. 8444 05:16:48,324 --> 05:16:50,693 WE ARE DEALING WITH PATIENTS WHO 8445 05:16:50,693 --> 05:16:54,163 ARE CRITICALLY ILL, FOR EXAMPLE, 8446 05:16:54,163 --> 05:16:55,898 PATIENTS THAT PRATIK MENTIONED, 8447 05:16:55,898 --> 05:16:58,034 WE COLLECT A LOT OF DATA IN OUR 8448 05:16:58,034 --> 05:16:59,535 SAMPLES BUT THE PATIENTS ARE 8449 05:16:59,535 --> 05:17:01,704 UNDER A LOT OF DISTRESS, THE 8450 05:17:01,704 --> 05:17:02,972 RATE IS NOT REALLY GREAT. 8451 05:17:02,972 --> 05:17:04,373 SO I'M THINKING IF WE NEEDED TO 8452 05:17:04,373 --> 05:17:06,709 LISTEN TO PATIENT, WHAT IS A 8453 05:17:06,709 --> 05:17:09,579 MINIMAL DATA ELEMENTS OR THE 8454 05:17:09,579 --> 05:17:11,314 SAMPLE ELEMENTS YOU WOULD LIKE 8455 05:17:11,314 --> 05:17:11,881 TO HAVE? 8456 05:17:11,881 --> 05:17:14,183 THAT WAY, IT WILL HELP US AS A 8457 05:17:14,183 --> 05:17:17,253 RESEARCHERS TO BE ABLE TO ANSWER 8458 05:17:17,253 --> 05:17:19,221 THE SCIENTIFIC QUESTIONS. 8459 05:17:19,221 --> 05:17:21,424 MEANWHILE WE CAN MITIGATE THE 8460 05:17:21,424 --> 05:17:24,293 STRESS, OUR PROCESS CAN IMPOSE 8461 05:17:24,293 --> 05:17:27,263 ON THE PATIENT. 8462 05:17:27,263 --> 05:17:28,764 THANK YOU. 8463 05:17:28,764 --> 05:17:30,433 >> MAYBE IT IS A QUESTION FOR 8464 05:17:30,433 --> 05:17:31,200 AZRA. 8465 05:17:31,200 --> 05:17:33,269 BECAUSE YOU WANT EVERYBODY TO 8466 05:17:33,269 --> 05:17:35,237 INSTRUMENT THEMSELVES, RIGHT? 8467 05:17:35,237 --> 05:17:36,639 QUANTIFIED SELF, YOU KNOW, 8468 05:17:36,639 --> 05:17:38,307 COLLECTING THEIR SAMPLES AND 8469 05:17:38,307 --> 05:17:40,209 RINGS AND HELMETS WITH 8470 05:17:40,209 --> 05:17:43,245 NEUROLOGIC SIGNAL? 8471 05:17:43,245 --> 05:17:45,982 I THINK THE PATIENTS ARE 8472 05:17:45,982 --> 05:17:47,550 CRITICAL BECAUSE I THINK THERE'S 8473 05:17:47,550 --> 05:17:49,719 A BIG EDUCATION GAP IN TERMS OF 8474 05:17:49,719 --> 05:17:52,254 THE INCIPIENT SYMPTOMS, 8475 05:17:52,254 --> 05:17:53,556 CIRCUMSTANCES THAT LEAD TO 8476 05:17:53,556 --> 05:17:56,759 INFECTION AS A PRECURSOR TO 8477 05:17:56,759 --> 05:17:57,627 DYSREGULATED IMMUNE RESPONSE AND 8478 05:17:57,627 --> 05:17:58,828 RISK OF MORTALITY. 8479 05:17:58,828 --> 05:18:03,566 I THINK THE TOOL SETS DO EXIST 8480 05:18:03,566 --> 05:18:05,434 TO INSTRUMENT -- HAVE PATIENTS 8481 05:18:05,434 --> 05:18:06,869 INSTRUMENTING SO THAT WE COULD 8482 05:18:06,869 --> 05:18:09,372 UNDERSTAND THOSE FACTORS, AND 8483 05:18:09,372 --> 05:18:11,107 THEY'RE GOING TO BE CRITICAL 8484 05:18:11,107 --> 05:18:12,341 PARTNERS TO DO THAT, BECAUSE I 8485 05:18:12,341 --> 05:18:14,777 DON'T THINK IT'S FEASIBLE FOR US 8486 05:18:14,777 --> 05:18:16,545 TO -- IT WOULD BE VERY 8487 05:18:16,545 --> 05:18:17,947 CHALLENGING FOR US TO DO THAT AT 8488 05:18:17,947 --> 05:18:18,581 SCALE WITHOUT PATIENTS BUYING 8489 05:18:18,581 --> 05:18:20,249 INTO THAT PROCESS AND ACTIVELY 8490 05:18:20,249 --> 05:18:21,851 BEING -- YOU KNOW, UNDERSTANDING 8491 05:18:21,851 --> 05:18:23,019 THE RATIONALE FOR WANTING TO 8492 05:18:23,019 --> 05:18:24,687 LINK UP THESE DATA WITH WHAT WE 8493 05:18:24,687 --> 05:18:26,889 ONLY OBSERVE DOWNSTREAM OR ONLY 8494 05:18:26,889 --> 05:18:30,826 IN PARTIAL WAYS. 8495 05:18:30,826 --> 05:18:32,695 SO I THINK WE DO NEED TO DO A 8496 05:18:32,695 --> 05:18:36,432 BETTER JOB IN THAT DOMAIN. 8497 05:18:36,432 --> 05:18:40,770 I THINK IT'S A CHALLENGING AREA. 8498 05:18:40,770 --> 05:18:50,613 >> AND ALONG THOSE LINES FOR AT 8499 05:18:50,613 --> 05:18:51,947 THE DIGITAL TWIN, I LIKE THAT 8500 05:18:51,947 --> 05:18:52,548 IDEA. 8501 05:18:52,548 --> 05:18:53,949 MAYBE WE NEED TO FOCUS ON 8502 05:18:53,949 --> 05:18:55,918 PRECISION MEDICINE INSTEAD OF 8503 05:18:55,918 --> 05:18:57,987 TRYING TO TACKLE THIS AS HAVING 8504 05:18:57,987 --> 05:18:58,988 ONE DEFINITION, ONE APPROACH, 8505 05:18:58,988 --> 05:19:00,723 MAYBE THIS HETEROGENEITY IS SO 8506 05:19:00,723 --> 05:19:02,525 HARD TO OVERCOME THAT WE NEED TO 8507 05:19:02,525 --> 05:19:04,360 FOCUS MORE ON EACH PATIENT 8508 05:19:04,360 --> 05:19:07,663 INDIVIDUALLY. 8509 05:19:07,663 --> 05:19:10,900 >> YES, SO WE -- INSTEAD OF ONE 8510 05:19:10,900 --> 05:19:11,834 COLOR WE SEE THE ENTIRE 8511 05:19:11,834 --> 05:19:12,101 SPECTRUM. 8512 05:19:12,101 --> 05:19:13,602 AND THAT IS HARD FOR HUMAN 8513 05:19:13,602 --> 05:19:15,838 BECAUSE WE TEND TO THINK MORE 8514 05:19:15,838 --> 05:19:16,172 REDUCTIONIST. 8515 05:19:16,172 --> 05:19:17,373 BUT I THINK THAT'S WHERE I SEE 8516 05:19:17,373 --> 05:19:18,641 TECHNOLOGY CAN HELP US, RIGHT? 8517 05:19:18,641 --> 05:19:21,343 I ALWAYS THINK THAT WE CAN GET A 8518 05:19:21,343 --> 05:19:25,915 SAW PER POWER OF A.I. TECHNOLOGY 8519 05:19:25,915 --> 05:19:27,216 BECAUSE -- INTO HUMAN WAY OF 8520 05:19:27,216 --> 05:19:28,551 THINKING THIS, THAT IS AGAIN 8521 05:19:28,551 --> 05:19:32,288 WHAT WE WANT, SO I WOULD JUST 8522 05:19:32,288 --> 05:19:37,426 ADD ON WHAT ARE YOU WHAT VINNYK 8523 05:19:37,426 --> 05:19:38,861 PATIENTS NEED TO BE EMPOWERED TO 8524 05:19:38,861 --> 05:19:40,096 UNDERSTAND THAT THERE IS NO 8525 05:19:40,096 --> 05:19:42,665 BETTER DOCTOR THAN YOURSELF. 8526 05:19:42,665 --> 05:19:44,166 YOU ARE YOUR BEST HELPER. 8527 05:19:44,166 --> 05:19:45,234 DEEP UNDERSTANDING HOW MUCH 8528 05:19:45,234 --> 05:19:47,136 CONTROL WE HAVE AS HUMANS, AND 8529 05:19:47,136 --> 05:19:49,905 HOW MUCH SIMPLE THINGS LIKE WHAT 8530 05:19:49,905 --> 05:19:52,742 WE EAT, HOW WE FEEL AND HOW WE 8531 05:19:52,742 --> 05:19:54,176 CONNECT INFLUENCE OUR HEALTH, 8532 05:19:54,176 --> 05:19:57,813 THAT IS ABSOLUTELY CRITICAL. 8533 05:19:57,813 --> 05:19:59,749 SO I'M MORE THAN A NEPHROLOGIST 8534 05:19:59,749 --> 05:20:01,283 AND INTENSIVIST, MORE AND MORE I 8535 05:20:01,283 --> 05:20:02,985 THINK OF IT, GO BACK TO PRIMARY 8536 05:20:02,985 --> 05:20:04,153 CARE, REALLY PREVENTION IS THE 8537 05:20:04,153 --> 05:20:05,921 KEY AND EDUCATION ABOUT 8538 05:20:05,921 --> 05:20:07,456 IMPORTANCE OF PREVENTION. 8539 05:20:07,456 --> 05:20:08,891 AND IMPORTANCE OF THESE TOOLS 8540 05:20:08,891 --> 05:20:11,327 THAT MAYBE ONE DAY THERE ARE 8541 05:20:11,327 --> 05:20:12,962 GOING TO BE HOSPITALS WHO CAN ON 8542 05:20:12,962 --> 05:20:15,164 CELL PHONE TELL YOU, NOT FEELING 8543 05:20:15,164 --> 05:20:16,365 WELL G TO DOCTOR. 8544 05:20:16,365 --> 05:20:17,800 THAT IS GOING TO BE AT THE TIP 8545 05:20:17,800 --> 05:20:20,770 OF THE HAND, NOW OUR JOB IS TO 8546 05:20:20,770 --> 05:20:22,505 EDUCATE OUR PATIENTS AND THINK 8547 05:20:22,505 --> 05:20:23,205 ABOUT THAT. 8548 05:20:23,205 --> 05:20:24,974 >> GREAT, WONDERFUL. 8549 05:20:24,974 --> 05:20:26,842 WELL, THANK YOU ALL FOR JUST A 8550 05:20:26,842 --> 05:20:29,111 TOUR OF WHAT THE OPPORTUNITIES 8551 05:20:29,111 --> 05:20:32,114 ARE FOR A.I. IN SEPSIS, AND I 8552 05:20:32,114 --> 05:20:33,415 THINK IT'S REALLY, REALLY 8553 05:20:33,415 --> 05:20:34,717 INTRIGUING TO SEE WHAT THESE 8554 05:20:34,717 --> 05:20:38,454 NEXT FIVE OR 10 YEARS WILL BRING 8555 05:20:38,454 --> 05:20:39,555 IN TERMS OF PRECISION MEDICINE 8556 05:20:39,555 --> 05:20:40,556 AND IN TERMS OF OUR 8557 05:20:40,556 --> 05:20:41,223 UNDERSTANDING OF THE FULL KIND 8558 05:20:41,223 --> 05:20:44,293 OF SPECTRUM OF SEPSIS FROM 8559 05:20:44,293 --> 05:20:46,095 COMMUNITIES ALL THE WAY DOWN TO 8560 05:20:46,095 --> 05:20:48,364 PROTEINS. 8561 05:20:48,364 --> 05:20:49,331 SO THANK YOU AGAIN FOR THAT, AND 8562 05:20:49,331 --> 05:20:50,866 WITH THAT, I'LL TURN IT OVER 8563 05:20:50,866 --> 05:20:52,234 BACK TO NITIN. 8564 05:20:52,234 --> 05:20:53,102 >> ALL RIGHT. 8565 05:20:53,102 --> 05:20:55,938 THANK YOU, VINNY. 8566 05:20:55,938 --> 05:20:58,607 AND FIRST OF ALL I WOULD LIKE TO 8567 05:20:58,607 --> 05:20:59,542 CONGRATULATE ALL THE SPEAKERS 8568 05:20:59,542 --> 05:21:04,513 HERE AND ALL THE CHAIRS FOR 8569 05:21:04,513 --> 05:21:06,315 KEEPING THE CLOCK OF TIME SO 8570 05:21:06,315 --> 05:21:06,515 MUCH. 8571 05:21:06,515 --> 05:21:09,385 WE ARE ONLY FIVE MINUTES BEHIND 8572 05:21:09,385 --> 05:21:11,153 IN THE ENTIRE DAY MEETING, WHICH 8573 05:21:11,153 --> 05:21:12,688 IS AMAZING. 8574 05:21:12,688 --> 05:21:16,325 SO THANK YOU ALL AGAIN FOR 8575 05:21:16,325 --> 05:21:17,660 KEEPING THIS ON TRACK. 8576 05:21:17,660 --> 05:21:19,061 LET'S TAKE A QUICK 10-MINUTE 8577 05:21:19,061 --> 05:21:22,231 BREAK, AND WE CAN RECONVENE AT 8578 05:21:22,231 --> 05:21:24,233 4:15, AND AFTER THAT, WE WILL 8579 05:21:24,233 --> 05:21:26,335 HAVING THE CONCLUDING REMARKS 8580 05:21:26,335 --> 05:21:27,736 FROM THE CHAIRS AND MODERATORS 8581 05:21:27,736 --> 05:21:28,904 FROM EACH SESSION AND THAT WILL 8582 05:21:28,904 --> 05:21:32,374 BE THE END OF THE MEETING AFTER 8583 05:21:32,374 --> 05:21:38,180 THAT. 8584 05:21:39,502 --> 05:21:41,605 I'M GUESSING THAT WE CAN DO 8585 05:21:41,605 --> 05:21:45,875 IT BY INVITING ALL THE CHAIRS 8586 05:21:45,875 --> 05:21:48,878 TOGETHER AS A JOINT PANEL 8587 05:21:48,878 --> 05:21:51,815 BECAUSE THERE'S BEEN A LOT OF 8588 05:21:51,815 --> 05:21:53,717 OVERLAP ACROSS THE SESSIONS WE 8589 05:21:53,717 --> 05:21:54,784 HAVE SEEN TODAY DURING THE 8590 05:21:54,784 --> 05:21:58,622 DISCUSSION PANELS. 8591 05:21:58,622 --> 05:22:01,925 SO FOR EXAMPLE, HOW THE CLINICAL 8592 05:22:01,925 --> 05:22:06,963 PRACTICES CAN OVERLAP THE 8593 05:22:06,963 --> 05:22:08,164 ONGOING RESEARCH AS THE 8594 05:22:08,164 --> 05:22:09,399 TECHNOLOGY INTERVENTIONS. 8595 05:22:09,399 --> 05:22:12,102 SO IT WOULD MAKE A LOT OF SENSE 8596 05:22:12,102 --> 05:22:14,104 TO ESTABLISH LINKS BETWEEN THE 8597 05:22:14,104 --> 05:22:14,971 THREE AREAS THAT WE HAVE 8598 05:22:14,971 --> 05:22:20,710 DISCUSSED T TODAY, AND CONCLUDE 8599 05:22:20,710 --> 05:22:22,112 THE TAKEAWAY LESSONS FROM THE 8600 05:22:22,112 --> 05:22:23,780 DISCUSSION, WHICH EACH SESSION 8601 05:22:23,780 --> 05:22:27,517 CHAIR CAN DO ONE AT A TIME 8602 05:22:27,517 --> 05:22:29,919 STARTING WITH SESSION ONE. 8603 05:22:29,919 --> 05:22:39,162 BUT IT COULD BE -- [INAUDIBLE] E 8604 05:22:39,162 --> 05:22:40,730 AS WELL AS NEEDED. 8605 05:22:40,730 --> 05:22:44,467 >> THANK YOU, NITIN, AND 8606 05:22:44,467 --> 05:22:45,335 DR. ASHANA IS GOING TO GO AHEAD 8607 05:22:45,335 --> 05:22:46,670 AND GIVE THE REPORT OUT FOR 8608 05:22:46,670 --> 05:22:56,880 SESSION ONE. 8609 05:22:58,548 --> 05:23:06,389 WE CAN'T HEAR YOU. 8610 05:23:06,389 --> 05:23:08,258 >> AUDIO ISSUES AGAIN, I 8611 05:23:08,258 --> 05:23:12,929 BELIEVE. 8612 05:23:12,929 --> 05:23:13,596 SOUNDS GOOD. 8613 05:23:13,596 --> 05:23:16,633 THANK YOU. 8614 05:23:16,633 --> 05:23:18,668 >> ARE YOU ABLE TO HEAR ME NOW? 8615 05:23:18,668 --> 05:23:18,868 GREAT. 8616 05:23:18,868 --> 05:23:19,936 >> YES, PERFECT. 8617 05:23:19,936 --> 05:23:20,804 >> ALL RIGHT. 8618 05:23:20,804 --> 05:23:21,037 AWESOME. 8619 05:23:21,037 --> 05:23:23,640 THANK YOU SO MUCH. 8620 05:23:23,640 --> 05:23:25,075 FIRST THANKS TO THE FOUR 8621 05:23:25,075 --> 05:23:26,176 PRESENTERS AND REALLY ALL OF THE 8622 05:23:26,176 --> 05:23:27,644 PRESENTERS TODAY. 8623 05:23:27,644 --> 05:23:29,279 THIS IS A FANTASTIC DAY AND I'VE 8624 05:23:29,279 --> 05:23:32,215 LEARNED A LOT. 8625 05:23:32,215 --> 05:23:33,850 SO I'LL JUST BE SUMMARIZING AS 8626 05:23:33,850 --> 05:23:35,652 YOU MENTIONED THE TALKS AS WELL 8627 05:23:35,652 --> 05:23:37,253 AS THE DISCUSSION FROM THE FIRST 8628 05:23:37,253 --> 05:23:38,722 SESSION ON DISPARITIES IN 8629 05:23:38,722 --> 05:23:44,294 SEPSIS. 8630 05:23:44,294 --> 05:23:46,062 WE HEARD TODAY SEPSIS IS A 8631 05:23:46,062 --> 05:23:46,663 LEADING CAUSE OF MORTALITY IN 8632 05:23:46,663 --> 05:23:47,630 THE WORLD AND THE U.S. 8633 05:23:47,630 --> 05:23:50,133 THERE ARE 11 MILLION ANNUAL 8634 05:23:50,133 --> 05:23:56,639 SEPSIS-RELATED DEATHS GLOBALLY. 8635 05:23:56,639 --> 05:23:58,174 DR. RUDD SHARED IT IS THE MOST 8636 05:23:58,174 --> 05:23:59,843 COMMON CAUSE OF DEATH WORLDWIDE 8637 05:23:59,843 --> 05:24:04,214 RESPONSIBLE FOR 1 IN 5 DEATHS 8638 05:24:04,214 --> 05:24:05,415 GLOBALLY, ALSO THE THIRD MOST 8639 05:24:05,415 --> 05:24:08,084 COMMON CAUSE OF DEATH IN U.S., 8640 05:24:08,084 --> 05:24:09,219 EQUIVALENT TO HEART ATTACKS AS 8641 05:24:09,219 --> 05:24:10,520 SHARED BY DR. MARTIN. 8642 05:24:10,520 --> 05:24:12,489 SURVIVAL IS NO DOUBT AN 8643 05:24:12,489 --> 05:24:14,124 IMPORTANT END POINT, HOWEVER, 8644 05:24:14,124 --> 05:24:16,426 THERE IS ALSO SUBSTANTIAL 8645 05:24:16,426 --> 05:24:17,327 MORBIDITY AMONG SURVIVORS OF 8646 05:24:17,327 --> 05:24:20,063 THIS GROUP. 8647 05:24:20,063 --> 05:24:21,397 THERE'S SUBSTANTIAL COGNITIVE, 8648 05:24:21,397 --> 05:24:23,633 PSYCHOLOGICAL AND FUNCTIONAL 8649 05:24:23,633 --> 05:24:28,505 IMPAIRMENTS AMONGST SURVIVORS OF 8650 05:24:28,505 --> 05:24:30,140 CRITICAL ILLNESS. 8651 05:24:30,140 --> 05:24:34,811 WE ALSO HEARD THOSE HARMS 8652 05:24:34,811 --> 05:24:35,512 DISPROPORTIONATELY ACCRUE TO 8653 05:24:35,512 --> 05:24:37,614 PATIENTS WHO EXPERIENCE SOCIAL 8654 05:24:37,614 --> 05:24:38,948 AND/OR ECONOMIC DISADVANTAGES. 8655 05:24:38,948 --> 05:24:41,184 SO DR. RUDD SHARED SOME OF HER 8656 05:24:41,184 --> 05:24:44,220 WORK IN LOW AND MIDDLE INCOME 8657 05:24:44,220 --> 05:24:45,155 COUNTRIES, AND WE ALSO HEARD IN 8658 05:24:45,155 --> 05:24:46,589 THE U.S. THAT PATIENTS WHO LIVE 8659 05:24:46,589 --> 05:24:48,958 IN RURAL AREAS, PATIENTS WHO 8660 05:24:48,958 --> 05:24:52,028 IDENTIFY AS BLACK, FO FOR EXAMP, 8661 05:24:52,028 --> 05:24:54,898 EXPERIENCE GREATER INCIDENCE AND 8662 05:24:54,898 --> 05:25:02,505 RISK OF MORTALITY FROM SEPSIS. 8663 05:25:02,505 --> 05:25:07,343 WE TALKED A LOT ABOUT POTENTIAL 8664 05:25:07,343 --> 05:25:08,845 ROOT CAUSES FOR THESE 8665 05:25:08,845 --> 05:25:09,712 DISPARITIES IN SEPSIS, AND 8666 05:25:09,712 --> 05:25:11,381 SPECIFICALLY THE INTERACTION OF 8667 05:25:11,381 --> 05:25:14,651 BIOLOGICAL AND SOCIAL RISK 8668 05:25:14,651 --> 05:25:14,884 FACTORS. 8669 05:25:14,884 --> 05:25:16,753 THERE WAS A LOT OF ATTENTION TO 8670 05:25:16,753 --> 05:25:17,754 NON-COMMUNICABLE DISEASES OR 8671 05:25:17,754 --> 05:25:19,823 CHRONIC ILLNESSES AND IN 8672 05:25:19,823 --> 05:25:25,428 PARTICULAR MULTI-MORBIDITY. 8673 05:25:25,428 --> 05:25:26,896 THE CONTRIBUTION OF 8674 05:25:26,896 --> 05:25:27,864 MULTI-MORBIDITY TO SEPSIS DEATH. 8675 05:25:27,864 --> 05:25:30,266 I WAS SURPRISED TO LEARN THAT 8676 05:25:30,266 --> 05:25:32,268 ABOUT 50% OF SEPSIS DEATHS CAN 8677 05:25:32,268 --> 05:25:33,903 BE ATTRIBUTED TO CHRONIC 8678 05:25:33,903 --> 05:25:35,638 ILLNESSES AND MULTI-MORBIDITY. 8679 05:25:35,638 --> 05:25:37,540 WE ALSO SPOKE A LOT ABOUT SOCIAL 8680 05:25:37,540 --> 05:25:38,775 RISK FACTORS THAT MAY CONTRIBUTE 8681 05:25:38,775 --> 05:25:43,947 TO SEPSIS RISK AND POOR OUTCO 8682 05:25:43,947 --> 05:25:44,214 OUTCOMES. 8683 05:25:44,214 --> 05:25:45,548 SO WE HEARD ABOUT TWO IMPORTANT 8684 05:25:45,548 --> 05:25:46,716 CONCEPTS WHICH MAY BE NEW TO 8685 05:25:46,716 --> 05:25:48,218 SOME OF THE AUDIENCE SO I'LL 8686 05:25:48,218 --> 05:25:49,185 JUST REDEFINE THEM. 8687 05:25:49,185 --> 05:25:51,821 WE HEARD ABOUT SYNDEMICS AND 8688 05:25:51,821 --> 05:25:53,857 ABOUT THIS CONCEPT OF 8689 05:25:53,857 --> 05:25:55,158 EMBODIMENT. 8690 05:25:55,158 --> 05:25:56,559 SYNDEMIC SIMPLY STANDS FOR 8691 05:25:56,559 --> 05:25:57,994 SYNERGISTIC EPIDEMIC, AND WHERE 8692 05:25:57,994 --> 05:25:59,362 THERE ARE SYNERGISTIC SOCIAL 8693 05:25:59,362 --> 05:26:01,531 RISKS AND BIOLOGICAL RISKS THAT 8694 05:26:01,531 --> 05:26:03,366 INTERACT WITH EACH OTHER TO 8695 05:26:03,366 --> 05:26:05,201 PRODUCE A HIGHER INCIDENCE OF 8696 05:26:05,201 --> 05:26:08,504 DISEASE IN A CERTAIN POPULATION. 8697 05:26:08,504 --> 05:26:11,274 SO DR. RUDD POSTULATED THAT THIS 8698 05:26:11,274 --> 05:26:13,776 MAY BE ONE POTENTIAL MECHANISM 8699 05:26:13,776 --> 05:26:17,046 BY WHICH WE ULTIMATELY SEE 8700 05:26:17,046 --> 05:26:18,314 DISPARITIES IN SEPSIS. 8701 05:26:18,314 --> 05:26:20,717 SO ONE EXAMPLE OF THAT IN 8702 05:26:20,717 --> 05:26:21,584 DR. MARTIN'S TALK IS WHEN HE 8703 05:26:21,584 --> 05:26:22,886 SHARED THAT IN THE STROKE BELT 8704 05:26:22,886 --> 05:26:24,254 OF THE UNITED STATES, THAT 8705 05:26:24,254 --> 05:26:25,588 THERE'S HIGHER SEPSIS-RELATED 8706 05:26:25,588 --> 05:26:27,657 MORTALITY IN THIS AREA THAN 8707 05:26:27,657 --> 05:26:29,559 RURAL SOUTHERN U.S. AND OF 8708 05:26:29,559 --> 05:26:32,195 COURSE THERE'S ALSO HUGE SOCIAL 8709 05:26:32,195 --> 05:26:34,397 BARRIERS TO HEALTHCARE IN THOSE 8710 05:26:34,397 --> 05:26:34,731 AREAS. 8711 05:26:34,731 --> 05:26:39,669 A LOT OF THOSE AREAS ACTUALLY 8712 05:26:39,669 --> 05:26:41,104 HAVE NO ACCESS TO ICUs IN 8713 05:26:41,104 --> 05:26:42,405 THEIR COMMUNITIES. 8714 05:26:42,405 --> 05:26:43,406 SO THAT WAS ONE IMPORTANT 8715 05:26:43,406 --> 05:26:45,174 CONCEPT THAT WE SHOULD TAKE AWAY 8716 05:26:45,174 --> 05:26:46,643 FROM THE TALKS THIS MORNING. 8717 05:26:46,643 --> 05:26:48,044 ANOTHER WAS THIS IDEA OF 8718 05:26:48,044 --> 05:26:50,313 EMBODIMENT THAT EXPOSURE TO 8719 05:26:50,313 --> 05:26:52,215 RACIALIZED AND ECONOMIC 8720 05:26:52,215 --> 05:26:53,650 INJUSTICE ACTUALLY RESULTS IN 8721 05:26:53,650 --> 05:26:55,084 BIOLOGICAL CHANGES. 8722 05:26:55,084 --> 05:26:56,819 WE HEARD ABOUT SOME WORK FROM 8723 05:26:56,819 --> 05:27:00,256 NANCY KRUEGER ABOUT EPIGENETIC 8724 05:27:00,256 --> 05:27:03,226 AGING, THE EXPOSURE TO SOCIAL 8725 05:27:03,226 --> 05:27:04,694 INJUSTICE, EVEN HISTORICAL 8726 05:27:04,694 --> 05:27:06,429 SOCIAL INJUSTICE SUCH AS LIVING 8727 05:27:06,429 --> 05:27:07,797 IN A STATE THAT PREVIOUSLY HAD 8728 05:27:07,797 --> 05:27:09,565 JIM CROW LAWS, EVEN TODAY FOR 8729 05:27:09,565 --> 05:27:11,100 FOLKS WHO WERE NOT ACTUALLY 8730 05:27:11,100 --> 05:27:12,502 EXPOSED TO THOSE LAWS, SIMPLY 8731 05:27:12,502 --> 05:27:14,103 LIVING IN A STATE THAT 8732 05:27:14,103 --> 05:27:17,273 HISTORICALLY HAD THOSE LAWS IS 8733 05:27:17,273 --> 05:27:18,675 ACTUALLY STRONGLY ASSOCIATED 8734 05:27:18,675 --> 05:27:19,876 WITH EPIGENETIC MARKERS OF 8735 05:27:19,876 --> 05:27:20,710 AGING. 8736 05:27:20,710 --> 05:27:21,477 SO THAT'S ONE IMPORTANT CONCEPT 8737 05:27:21,477 --> 05:27:23,179 THAT WE SHOULD TAKE AWAY, IS 8738 05:27:23,179 --> 05:27:24,347 THIS DISTINCTION BETWEEN 8739 05:27:24,347 --> 05:27:29,519 BIOLOGICAL AND CHRONOLOGICAL AGE 8740 05:27:29,519 --> 05:27:30,586 AND HOW THAT MAY INFLUENCE 8741 05:27:30,586 --> 05:27:31,788 SEPSIS RISK AND OUTCOMES. 8742 05:27:31,788 --> 05:27:33,122 THIS IS ESPECIALLY RELEVANT 8743 05:27:33,122 --> 05:27:35,258 BECAUSE DR. MARTIN SHIRRED 8744 05:27:35,258 --> 05:27:39,729 THERE'S AN EXPONENTIAL INCREASE 8745 05:27:39,729 --> 05:27:41,130 IN SUBSTANCE INCIDENCE. 8746 05:27:41,130 --> 05:27:43,833 WE ALSO HEARD ABOUT ENDOTHELIAL 8747 05:27:43,833 --> 05:27:44,701 DAMAGE AS A POTENTIAL COMMON 8748 05:27:44,701 --> 05:27:46,336 CAUSE OF CHRONIC ILLNESS IN 8749 05:27:46,336 --> 05:27:48,972 SEPSIS, BUT THIS WAS IDENTIFIED 8750 05:27:48,972 --> 05:27:53,109 AS A KNOWLEDGE GAP THAT REQUIRES 8751 05:27:53,109 --> 05:27:53,609 ADDITIONAL STUDY. 8752 05:27:53,609 --> 05:27:58,748 TO DR. AGARWAL'S POINT TO THE 8753 05:27:58,748 --> 05:27:59,449 INTERCONNECTION BETWEEN THE 8754 05:27:59,449 --> 05:28:00,650 THREE SESSIONS TODAY, I THINK 8755 05:28:00,650 --> 05:28:03,519 THIS IS AN IMPORTANT ONE THAT 8756 05:28:03,519 --> 05:28:04,387 CONNECTS TO THE SECOND SESSION 8757 05:28:04,387 --> 05:28:06,889 AND COULD BE AN IMPORTANT AREA 8758 05:28:06,889 --> 05:28:08,925 OF COLLABORATION BETWEEN 8759 05:28:08,925 --> 05:28:10,860 POTENTIALLY SOCIAL SCIENTISTS 8760 05:28:10,860 --> 05:28:17,433 AND TRANSLATIONAL SCIENTISTS. 8761 05:28:17,433 --> 05:28:18,801 THERE WAS A LOT OF DISCUSSION IN 8762 05:28:18,801 --> 05:28:20,303 THE PANEL DISCUSSION ABOUT 8763 05:28:20,303 --> 05:28:21,637 GENETIC RISK FOR SEPSIS AND 8764 05:28:21,637 --> 05:28:25,908 BECAUSE WE HAD TALKED ABOUT THE 8765 05:28:25,908 --> 05:28:31,614 LACK OF EVIDENCE FOR THE 8766 05:28:31,614 --> 05:28:33,349 ASSOCIATION BETWEEN GENETICS AND 8767 05:28:33,349 --> 05:28:34,384 RACE IN THE UNITED STATES. 8768 05:28:34,384 --> 05:28:37,553 I THOUGHT I WOULD JUST SHARE 8769 05:28:37,553 --> 05:28:39,088 SOME OF THE EVIDENCE THAT DOES 8770 05:28:39,088 --> 05:28:43,559 EXIST SO WE HAD REFERENCE TO 8771 05:28:43,559 --> 05:28:46,662 SARAH TISHKOFF'S WORK. 8772 05:28:46,662 --> 05:28:50,199 THESE ARE SOME KEY PHRASES FROM 8773 05:28:50,199 --> 05:28:51,367 HER ARTICLE SO I'LL JUST READ 8774 05:28:51,367 --> 05:28:51,934 THEM OUT. 8775 05:28:51,934 --> 05:28:54,837 SHE SAYS THAT BECAUSE MODERN 8776 05:28:54,837 --> 05:28:56,039 HUMANS ORIGINATED IN AFRICA AND 8777 05:28:56,039 --> 05:28:57,673 HAVE ADAPTED TO DIVERSE 8778 05:28:57,673 --> 05:28:59,575 ENVIRONMENTS, AFRICAN 8779 05:28:59,575 --> 05:29:01,310 POPULATIONS HAVE HIGH LEVELS OF 8780 05:29:01,310 --> 05:29:03,713 GENETIC AND PHENOTYPIC 8781 05:29:03,713 --> 05:29:04,981 DIVERSITY, AND IN FACT AFRICAN 8782 05:29:04,981 --> 05:29:06,082 POPULATIONS HAVE THE HIGHEST 8783 05:29:06,082 --> 05:29:07,517 LEVELS OF GENETIC VARIATION 8784 05:29:07,517 --> 05:29:09,786 AMONG ALL HUMANS, THAT CANNOT BE 8785 05:29:09,786 --> 05:29:12,355 THE CASE AMONG INDIVIDUALS WHO 8786 05:29:12,355 --> 05:29:13,556 WE CLASSIFY AS BLACK IN THE 8787 05:29:13,556 --> 05:29:14,223 UNITED STATES, THAT THERE WOULD 8788 05:29:14,223 --> 05:29:15,992 BE A COMMON GENETIC ROOT CAUSE 8789 05:29:15,992 --> 05:29:19,395 TO EXPLAIN THE HIGHER PREVALENCE 8790 05:29:19,395 --> 05:29:23,332 OF SEPSIS IN THAT POPULATION. 8791 05:29:23,332 --> 05:29:27,003 AND SHE ALSO NOTES IN HER WORK 8792 05:29:27,003 --> 05:29:29,439 THAT GENETIC DIVERSITY DECLINES 8793 05:29:29,439 --> 05:29:30,640 WITH DISTANCE FROM AFRICA 8794 05:29:30,640 --> 05:29:33,309 CONSISTENT WITH PROPOSED SERIAL 8795 05:29:33,309 --> 05:29:34,277 FOUNDER EFFECTS, WHICH MEANS 8796 05:29:34,277 --> 05:29:35,912 THAT IN INDIVIDUALS WITH 8797 05:29:35,912 --> 05:29:40,516 EUROPEAN ANCESTRY THERE'S MORE 8798 05:29:40,516 --> 05:29:41,250 HOMOGENEITY. 8799 05:29:41,250 --> 05:29:43,386 AS SOMEONE WHO STUDIES HEALTH 8800 05:29:43,386 --> 05:29:45,154 EQUITY, I AM A BIG FAN OF 8801 05:29:45,154 --> 05:29:46,522 FRAMEWORKS AND THEORIES AND I 8802 05:29:46,522 --> 05:29:48,157 WILL JUST SHARE ONE OF MY 8803 05:29:48,157 --> 05:29:50,993 FAVORITE ONES BECAUSE I THINK 8804 05:29:50,993 --> 05:29:52,295 THESE ARE REALLY USEFUL FRAME 8805 05:29:52,295 --> 05:29:53,763 WORKS FOR ORGANIZING OUR STUDY 8806 05:29:53,763 --> 05:29:55,098 OF CERTAINLY SOCIAL SCIENCE 8807 05:29:55,098 --> 05:29:56,833 TOPICS BUT POTENTIALLY OTHER 8808 05:29:56,833 --> 05:30:00,870 TOPICS AS WELL. 8809 05:30:00,870 --> 05:30:02,605 THIS IS A THEORY PROPOSED BY 8810 05:30:02,605 --> 05:30:03,806 NANCY KRUEGER MORE THAN 10 YEARS 8811 05:30:03,806 --> 05:30:04,373 AGO NOW. 8812 05:30:04,373 --> 05:30:06,442 IT'S CALLED THE ECOSOCIAL 8813 05:30:06,442 --> 05:30:06,676 THEORY. 8814 05:30:06,676 --> 05:30:08,878 IT'S A FRAMEWORK TO UNDERSTAND 8815 05:30:08,878 --> 05:30:10,413 SOCIAL INEQUITIES AND HEALTH 8816 05:30:10,413 --> 05:30:12,048 OUTCOMES. 8817 05:30:12,048 --> 05:30:14,083 NOT ALL OF THESE AREAS ARE 8818 05:30:14,083 --> 05:30:14,717 RELEVANT TO WHAT WE'RE TALKING 8819 05:30:14,717 --> 05:30:16,152 ABOUT TODAY, SO I'LL JUST HIDE 8820 05:30:16,152 --> 05:30:17,954 SOME OF THESE SO WE CAN FOCUS ON 8821 05:30:17,954 --> 05:30:22,091 WHAT IS RELEVANT. 8822 05:30:22,091 --> 05:30:23,626 SO THE CENTER OF THIS FIGURE IS 8823 05:30:23,626 --> 05:30:27,396 WHAT WE OBSERVE IN OUR CLINICAL 8824 05:30:27,396 --> 05:30:28,631 PRACTICE AND OUR DATA. 8825 05:30:28,631 --> 05:30:30,833 WE SEE POPULATION DISTRIBUTION 8826 05:30:30,833 --> 05:30:32,468 OF DISEASE AND HEALTH, AND THEY 8827 05:30:32,468 --> 05:30:36,439 SEEM TO DIFFER BY RACIAL -- BY 8828 05:30:36,439 --> 05:30:37,540 RACE, ETHNICITY, CLASS. 8829 05:30:37,540 --> 05:30:38,841 WE TALKED A LITTLE BIT ABOUT 8830 05:30:38,841 --> 05:30:40,710 GENDER TODAY, NOT SO MUCH ABOUT 8831 05:30:40,710 --> 05:30:41,711 SEXUALITY BECAUSE THIS IS WHAT 8832 05:30:41,711 --> 05:30:42,712 WE OBSERVE. 8833 05:30:42,712 --> 05:30:45,681 BUT WHAT UNDERLIES THIS, AND IF 8834 05:30:45,681 --> 05:30:54,991 WE ADVANCE AGAIN P THESE ARE THE 8835 05:30:54,991 --> 05:30:56,225 ROOT CAUSES SHE POSTULATES. 8836 05:30:56,225 --> 05:30:57,293 AGAIN WE TALKED ABOUT A LOT OF 8837 05:30:57,293 --> 05:30:57,760 THESE TODAY. 8838 05:30:57,760 --> 05:30:59,662 WE TALKED ABOUT THE CONCEPT OF 8839 05:30:59,662 --> 05:31:00,630 EMBODIMENT, WHAT ARE THE 8840 05:31:00,630 --> 05:31:02,064 PATHWAYS OF EMBODIMENT. 8841 05:31:02,064 --> 05:31:03,900 I THINK ONE KEY THING WE SHOULD 8842 05:31:03,900 --> 05:31:04,934 TAKE YOU A WAY TODAY IS WE 8843 05:31:04,934 --> 05:31:07,236 REALLY DON'T KNOW PRECISELY WHAT 8844 05:31:07,236 --> 05:31:13,209 THOSE PATHWAYS OF EMBODIMENT ON 8845 05:31:13,209 --> 05:31:15,378 EPIGENETIC AGING IS DEFINITELY 8846 05:31:15,378 --> 05:31:17,613 AN AREA WE SHOULD FOCUS ON IN 8847 05:31:17,613 --> 05:31:17,980 FUTURE RESEARCH. 8848 05:31:17,980 --> 05:31:19,382 WE ALSO TALKED ABOUT THE 8849 05:31:19,382 --> 05:31:21,217 CUMULATIVE INTERPLAY BETWEEN 8850 05:31:21,217 --> 05:31:22,218 EXPOSURE SUSCEPTIBILITY AND 8851 05:31:22,218 --> 05:31:23,252 RESISTANCE. 8852 05:31:23,252 --> 05:31:24,453 AND THAT ALL OF THIS IS SORT OF 8853 05:31:24,453 --> 05:31:27,190 FILTERED THROUGH THE LENS OF 8854 05:31:27,190 --> 05:31:28,391 POLITICAL ECONOMY AND POLITICAL 8855 05:31:28,391 --> 05:31:33,229 ECOLOGY, WHICH MEANS THAT 8856 05:31:33,229 --> 05:31:33,863 PATIENTS EXPERIENCE BIOLOGICAL 8857 05:31:33,863 --> 05:31:35,565 RISK BUT HOW THEY ACCESS THE 8858 05:31:35,565 --> 05:31:36,432 HEALTHCARE SYSTEM ALSO DEPENDS 8859 05:31:36,432 --> 05:31:39,001 ON THE COUNTRY IN WHICH THEY 8860 05:31:39,001 --> 05:31:41,604 LIVE, SO WE HAVE A DEFECTIVE 8861 05:31:41,604 --> 05:31:42,939 SYSTEM OF WEALTH-BASED INSURANCE 8862 05:31:42,939 --> 05:31:44,640 AND HEALTHCARE ACCESS IN THIS 8863 05:31:44,640 --> 05:31:45,508 COUNTRY, AND INSURANCE IS TIED 8864 05:31:45,508 --> 05:31:46,709 TO THE JOB THAT YOU HAVE FOR 8865 05:31:46,709 --> 05:31:48,010 VERY MANY PEOPLE, AND THE TYPES 8866 05:31:48,010 --> 05:31:49,378 OF HOSPITALS THAT YOU HAVE 8867 05:31:49,378 --> 05:31:50,479 ACCESS TO DEPENDS ON WHERE YOU 8868 05:31:50,479 --> 05:31:51,614 LIVE. 8869 05:31:51,614 --> 05:31:53,916 AND SO THAT'S WHY ALL OF THESE 8870 05:31:53,916 --> 05:31:56,953 MECHANISMS ARE SORT OF FILTERED 8871 05:31:56,953 --> 05:31:57,920 THROUGH THAT POLITICAL ECONOMY 8872 05:31:57,920 --> 05:31:58,487 AND ECOLOGY. 8873 05:31:58,487 --> 05:31:59,789 AND THEN THE LAST THING SHE 8874 05:31:59,789 --> 05:32:01,924 TALKS ABOUT IS ACCOUNTABILITY IN 8875 05:32:01,924 --> 05:32:02,892 AGENCY, WHICH ALSO MEANS THAT 8876 05:32:02,892 --> 05:32:05,294 WHEN WE'RE STUDYING HEALTH 8877 05:32:05,294 --> 05:32:06,729 EQUITY -- HEALTH INEQUITIES, 8878 05:32:06,729 --> 05:32:07,230 IT'S VERY IMPORTANT TO 8879 05:32:07,230 --> 05:32:10,266 UNDERSTAND HOW POWER IS 8880 05:32:10,266 --> 05:32:12,535 DISTRIBUTED IN THE HEALTHCARE 8881 05:32:12,535 --> 05:32:20,509 SYSTEM AND THAT SHOULD DICTA 8882 05:32:20,509 --> 05:32:21,277 DICTATE -- IT IS THE CASE THAT 8883 05:32:21,277 --> 05:32:22,044 THE HEALTHCARE SYSTEM HAS POWER 8884 05:32:22,044 --> 05:32:23,246 TO CHANGE THE WAY IT DELIVERS 8885 05:32:23,246 --> 05:32:24,880 CARE TO THOSE PATIENTS AND SO 8886 05:32:24,880 --> 05:32:28,551 BECAUSE WE HAVE MUCH MORE POWER 8887 05:32:28,551 --> 05:32:29,885 THAN PATIENTS, AND I WOULD 8888 05:32:29,885 --> 05:32:31,287 CONTEND THAT OUR FOCUS OF 8889 05:32:31,287 --> 05:32:33,656 SCHOLARSHIP REALLY SHOULD BE ON 8890 05:32:33,656 --> 05:32:44,166 THE HEALTHCARE SYSTEM AS WELL. 8891 05:32:45,001 --> 05:32:46,135 SO WE REALLY TALKED ABOUT WHAT 8892 05:32:46,135 --> 05:32:47,536 IS THE CONTRIBUTION OF 8893 05:32:47,536 --> 05:32:49,939 CLINICIANS AND HEALTHCARE 8894 05:32:49,939 --> 05:32:50,840 SYSTEMS FOR DISPARITIES IN 8895 05:32:50,840 --> 05:32:51,274 SEPSIS. 8896 05:32:51,274 --> 05:32:55,411 AND THIS ON THE LEFT IS ONE OF 8897 05:32:55,411 --> 05:32:56,412 MY FAVORITE FIGURES. 8898 05:32:56,412 --> 05:32:57,880 AGAIN, IT'S A THEORY TO 8899 05:32:57,880 --> 05:33:01,617 UNDERSTAND INEQUITIES IN 8900 05:33:01,617 --> 05:33:02,885 HEALTHCARE, IT WAS ORIGINALLY 8901 05:33:02,885 --> 05:33:04,353 PROPOSED IN 1971 AND UPDATED IN 8902 05:33:04,353 --> 05:33:04,854 2021. 8903 05:33:04,854 --> 05:33:06,155 IT'S THE DISPROPORTIONATE CARE 8904 05:33:06,155 --> 05:33:09,125 LAW, AND PACEICA BASICALLY WHATS 8905 05:33:09,125 --> 05:33:12,795 SHOWS IS AS ON THE X AXIS, 8906 05:33:12,795 --> 05:33:14,096 DISADVANTAGE ACCRUES TO 8907 05:33:14,096 --> 05:33:14,964 POPULATIONS. 8908 05:33:14,964 --> 05:33:18,901 THE Y AXIS WE SEE THAT THERE IS 8909 05:33:18,901 --> 05:33:20,536 RELATIVELY LESS RESOURCE INPUT 8910 05:33:20,536 --> 05:33:21,537 PER CAPITA. 8911 05:33:21,537 --> 05:33:22,638 LET ME JUST EXPLAIN WHAT THAT 8912 05:33:22,638 --> 05:33:23,172 MEANS. 8913 05:33:23,172 --> 05:33:24,373 ON THE LEFT-HAND SIDE OF THIS 8914 05:33:24,373 --> 05:33:28,811 GRAPH, WHAT WE SEE IS THAT VERY 8915 05:33:28,811 --> 05:33:29,478 ADVANTAGED, VERY WEALTHY 8916 05:33:29,478 --> 05:33:31,547 POPULATIONS HAVE A NEED FOR 8917 05:33:31,547 --> 05:33:33,182 HEALTHCARE, OF COURSE, BUT THEY 8918 05:33:33,182 --> 05:33:35,184 HAVE EXCESS AVAILABILITY OF 8919 05:33:35,184 --> 05:33:37,386 HEALTHCARE RESOURCES. 8920 05:33:37,386 --> 05:33:39,355 THESE ARE THE PATIENTS WHO HAVE 8921 05:33:39,355 --> 05:33:40,756 ACCESS TO LIKE FOR MYSELF FOR 8922 05:33:40,756 --> 05:33:42,491 EXAMPLE, I DON'T NEED A REFERRAL 8923 05:33:42,491 --> 05:33:43,526 TO SEE ANY SPECIALIST THAT I 8924 05:33:43,526 --> 05:33:44,260 WANT. 8925 05:33:44,260 --> 05:33:45,895 I HAVE EXCESS AVAILABILITY OF 8926 05:33:45,895 --> 05:33:48,030 HEALTHCARE RESOURCES AVAILABLE 8927 05:33:48,030 --> 05:33:48,230 TO ME. 8928 05:33:48,230 --> 05:33:49,565 ON THE OTHER HAND, ON THE 8929 05:33:49,565 --> 05:33:50,766 RIGHT-HAND SIDE OF THE GRAPH, 8930 05:33:50,766 --> 05:33:54,670 MORE DISADVANTAGED POPULATIONS 8931 05:33:54,670 --> 05:33:56,839 HAVE COMPARATIVELY GREATER NEED 8932 05:33:56,839 --> 05:33:57,940 BUT RELATIVELY LESS AVAILABILITY 8933 05:33:57,940 --> 05:33:59,809 OF HIGH QUALITY HEALTHCARE 8934 05:33:59,809 --> 05:34:01,177 RESOURCES SO THEY ULTIMATELY 8935 05:34:01,177 --> 05:34:03,679 HAVE A GREATER UNMET NEED. 8936 05:34:03,679 --> 05:34:04,680 WE SEE THIS IN SEPSIS CARE IN 8937 05:34:04,680 --> 05:34:06,215 THE U.S. AS WELL, AND IN THE 8938 05:34:06,215 --> 05:34:08,684 RURAL U.S., THERE'S ABSOLUTE 8939 05:34:08,684 --> 05:34:11,854 SCARCITY OF CRITICAL CARE 8940 05:34:11,854 --> 05:34:13,189 RESOURCES. 8941 05:34:13,189 --> 05:34:14,824 AS I MENTIONED MANY COMMUNITIES 8942 05:34:14,824 --> 05:34:17,059 WITH NO ICU BEDS AND THEN WILL 8943 05:34:17,059 --> 05:34:20,329 LARGER CITIES THERE'S RELATIVE 8944 05:34:20,329 --> 05:34:21,764 SCARCITY OF CRITICAL CARE 8945 05:34:21,764 --> 05:34:22,732 RESOURCES. 8946 05:34:22,732 --> 05:34:24,567 DR. DONELY SPOKE A LOT ABOUT 8947 05:34:24,567 --> 05:34:25,234 VARIABILITY -- WE KNOW WHAT WE 8948 05:34:25,234 --> 05:34:27,203 SHOULD BE DOING AND YET WE DON'T 8949 05:34:27,203 --> 05:34:28,571 DOUGH THOSE THINGS CONSISTENTLY 8950 05:34:28,571 --> 05:34:30,005 AND THAT REALLY VARIES BASED ON 8951 05:34:30,005 --> 05:34:31,407 THE DEMOGRAPHICS OF THE 8952 05:34:31,407 --> 05:34:33,676 HOSPITAL, SO THAT IS A GROWING 8953 05:34:33,676 --> 05:34:34,110 CAUSE OF DISPARITY. 8954 05:34:34,110 --> 05:34:35,544 AND ANOTHER WE DIDN'T GET INTO 8955 05:34:35,544 --> 05:34:39,915 TOO MUCH IS PAYING PENALTIES FOR 8956 05:34:39,915 --> 05:34:41,951 ADHERING TO SEPSIS BUNDLES HOW 8957 05:34:41,951 --> 05:34:46,222 THEY MAY ACTUALLY PARADOXLY WORK 8958 05:34:46,222 --> 05:34:49,825 INTO -- FOR ADHERING TO SEPSIS 8959 05:34:49,825 --> 05:34:51,427 BUNDLES -- EVEN WITHIN HOSPITALS 8960 05:34:51,427 --> 05:34:52,528 DURING TIMES OF STRAIN, THERE 8961 05:34:52,528 --> 05:34:55,164 CAN BE BREAKDOWNS IN THESE 8962 05:34:55,164 --> 05:35:01,003 EVIDENCE-BASED CARE PROCESSES. 8963 05:35:01,003 --> 05:35:07,309 WE'VE COVERED ALL LOI THE LOT S 8964 05:35:07,309 --> 05:35:08,644 ALREADY, BUT THE MAIN KNOWLEDGE 8965 05:35:08,644 --> 05:35:10,112 GAPS WE HIGHLIGHTED WERE 8966 05:35:10,112 --> 05:35:13,949 BIOLOGICAL MECHANISMS THAT LINK 8967 05:35:13,949 --> 05:35:16,352 SOCIAL RISKS, AND THE SECOND WAS 8968 05:35:16,352 --> 05:35:18,554 ABOUT INTERSECTION BETWEEN 8969 05:35:18,554 --> 05:35:19,388 PATIENT CHARACTERISTICS, 8970 05:35:19,388 --> 05:35:21,323 CERTAINLY THE POTENTIALLY PAYING 8971 05:35:21,323 --> 05:35:22,324 GREATER ATTENTION TO THE CARE 8972 05:35:22,324 --> 05:35:25,561 DELIVERY PROCESSES AND HOSPITAL 8973 05:35:25,561 --> 05:35:28,130 CHARACTERISTICS. 8974 05:35:28,130 --> 05:35:30,099 AND THEN FINALLY, WE'LL END WITH 8975 05:35:30,099 --> 05:35:31,267 POTENTIAL SOLUTIONS AND FIRST 8976 05:35:31,267 --> 05:35:33,469 I'LL JUST NOTE THAT THERE AREN'T 8977 05:35:33,469 --> 05:35:34,637 ENOUGH ON THIS SLIDE BECAUSE OUR 8978 05:35:34,637 --> 05:35:37,039 FIELD REALLY HAS NOT MOVED IN 8979 05:35:37,039 --> 05:35:41,277 THIS SPACE YET. 8980 05:35:41,277 --> 05:35:42,645 BUT MAYBE THAT WILL BE FOCUS OF 8981 05:35:42,645 --> 05:35:44,747 THE NEXT ITERATION OF THIS 8982 05:35:44,747 --> 05:35:45,548 WORKSHOP. 8983 05:35:45,548 --> 05:35:47,249 ONE POTENTIAL SOLUTION IS USING 8984 05:35:47,249 --> 05:35:48,417 IMPLEMENTATION SCIENCE TO 8985 05:35:48,417 --> 05:35:49,752 STANDARDIZE EVIDENCE-BASED CARE 8986 05:35:49,752 --> 05:35:50,953 DELIVERY AND REALLY CREATING 8987 05:35:50,953 --> 05:35:53,322 SEPSIS CARE BUNDLES THAT ARE 8988 05:35:53,322 --> 05:35:56,058 INDIVIDUALIZED TO CONTEXT, SO 8989 05:35:56,058 --> 05:35:59,195 EVEN TO LOW RESOURCE CARE 8990 05:35:59,195 --> 05:35:59,762 SETTINGS. 8991 05:35:59,762 --> 05:36:01,497 AND DR. CHESLEY SPOKE ABOUT 8992 05:36:01,497 --> 05:36:02,865 INCLUSION OF CRITICAL ACCESS IN 8993 05:36:02,865 --> 05:36:04,133 MINORITY SERVING HOSPITALS IN 8994 05:36:04,133 --> 05:36:07,803 RESEARCH TO DEVELOP THOSE 8995 05:36:07,803 --> 05:36:08,737 CONTEXTUALLY TAILORED SOLUTIONS. 8996 05:36:08,737 --> 05:36:09,839 THERE WAS A LOT OF DISCUSSION 8997 05:36:09,839 --> 05:36:11,740 ABOUT MOVING RESEARCH UPSTREAM, 8998 05:36:11,740 --> 05:36:12,575 HOW DO WE REALLY THINK ABOUT 8999 05:36:12,575 --> 05:36:13,676 PRIMARY AND SECONDARY 9000 05:36:13,676 --> 05:36:14,543 PREINVESTIGATION OF SEPSIS. 9001 05:36:14,543 --> 05:36:17,513 SOME IDEAS THAT WERE SHARED WERE 9002 05:36:17,513 --> 05:36:19,615 MORE PRECISE RISK STIDGES FOR 9003 05:36:19,615 --> 05:36:20,783 PREVENTIVE CARE DELIVERY. 9004 05:36:20,783 --> 05:36:23,219 HOW DO WE USE WEARABLES, 9005 05:36:23,219 --> 05:36:24,487 PATIENT-REPORTED OUTCOMES, THIS 9006 05:36:24,487 --> 05:36:26,121 IS POTENTIALLY A CONNECTION WITH 9007 05:36:26,121 --> 05:36:28,657 THE THIRD SET OF TALKS, FOCUSING 9008 05:36:28,657 --> 05:36:29,458 ON A.I. 9009 05:36:29,458 --> 05:36:31,894 HOW DO WE USE THE TECHNOLOGY 9010 05:36:31,894 --> 05:36:33,729 THAT'S AVAILABLE TO US TO REALLY 9011 05:36:33,729 --> 05:36:35,664 IDENTIFY THE INDIVIDUALS WHO ARE 9012 05:36:35,664 --> 05:36:36,999 AT HIGHER RISK OR HIGHEST RISK 9013 05:36:36,999 --> 05:36:38,167 FOR DEVELOPING SEPSIS AND THEN 9014 05:36:38,167 --> 05:36:40,436 HOW DO WE CREATE CULTURALLY 9015 05:36:40,436 --> 05:36:41,637 TAILORED EDUCATION AND OUTREACH 9016 05:36:41,637 --> 05:36:43,606 TO REDUCE THEIR RISK. 9017 05:36:43,606 --> 05:36:51,380 AND THE RESULTS OF DISCUSSION -- 9018 05:36:51,380 --> 05:36:53,916 PRESEPSIS, HOW DO WE STANDARDIZE 9019 05:36:53,916 --> 05:36:57,219 THE MESH MEASUREMENT OF THAT FR 9020 05:36:57,219 --> 05:36:57,953 RESEARCH. 9021 05:36:57,953 --> 05:37:02,424 THEN A DISCUSSION ENGAGING ALL 9022 05:37:02,424 --> 05:37:03,425 RELEVANT PARTIES NOTING THAT 9023 05:37:03,425 --> 05:37:06,495 EVERYBODY WHO SPOKE TODAY IS A 9024 05:37:06,495 --> 05:37:07,730 PHYSICIAN -- OR NOT A PHYSICIAN, 9025 05:37:07,730 --> 05:37:09,198 I SHOULD SAY, A SCHOLAR AT A 9026 05:37:09,198 --> 05:37:10,432 VERY WELL RESOURCED HOSPITAL, 9027 05:37:10,432 --> 05:37:11,667 AND ARE THOSE THE ONLY PEOPLE 9028 05:37:11,667 --> 05:37:13,202 THAT NEED TO BE AT THE TABLE IF 9029 05:37:13,202 --> 05:37:15,404 WE WANT TO DO THIS WORK VERY 9030 05:37:15,404 --> 05:37:15,738 WELL. 9031 05:37:15,738 --> 05:37:18,641 AND THEN FINALLY, ARE THERE NIH 9032 05:37:18,641 --> 05:37:23,012 MECHANISMS THAT COULD ENCOURAGE 9033 05:37:23,012 --> 05:37:26,181 MULTIDISCIPLINARY RESEARCH WITH 9034 05:37:26,181 --> 05:37:27,816 THE SOCIAL SCIENCES, AND I WILL 9035 05:37:27,816 --> 05:37:28,117 END THERE. 9036 05:37:28,117 --> 05:37:38,294 THANK YOU. 9037 05:37:44,867 --> 05:37:48,470 >> I THINK DR. BAE WILL GIVE THE 9038 05:37:48,470 --> 05:37:48,804 REPORT. 9039 05:37:48,804 --> 05:37:57,279 SO GO AHEAD, PLEASE. 9040 05:37:57,279 --> 05:37:58,581 >> HELLO, EVERYONE. 9041 05:37:58,581 --> 05:38:01,116 THIS IS FOR THE REPORT OUT OF 9042 05:38:01,116 --> 05:38:04,386 SUMMARY FOR SESSION TWO. 9043 05:38:04,386 --> 05:38:09,258 SO THE SESSION WAS CHAIRED BY 9044 05:38:09,258 --> 05:38:15,731 DR. PRITHU SUNDD AND MYSELF FROM 9045 05:38:15,731 --> 05:38:17,132 THE NHLBI PRIDE SCHOLAR PROGRAM. 9046 05:38:17,132 --> 05:38:19,435 WE DISCUSSED ABOUT MECHANISM 9047 05:38:19,435 --> 05:38:20,736 UNDERLYING THROMBOINFLAMMATION 9048 05:38:20,736 --> 05:38:25,641 RESPONSE IN SEPSIS. 9049 05:38:25,641 --> 05:38:27,276 WE FIRST WANT TO THANK OUR 9050 05:38:27,276 --> 05:38:30,446 SPEAKERS, DR. ZHENYU LI WHO 9051 05:38:30,446 --> 05:38:34,049 DISCUSSED ABOUT HOW PYROPTOSIS 9052 05:38:34,049 --> 05:38:35,384 DRIVES COAGULATION IN SEPSIS. 9053 05:38:35,384 --> 05:38:42,024 AND DR. KANDACE GOLLO MP, HOW 9054 05:38:42,024 --> 05:38:43,993 PF4 AND NEUTROPHIL EXTRACELLULAR 9055 05:38:43,993 --> 05:38:47,262 TRAPS PROMOTE PATHOGENESIS OF 9056 05:38:47,262 --> 05:38:49,198 SEPSIS, THEN DR. NIGEL MACKMAN 9057 05:38:49,198 --> 05:38:52,768 CONTINUED TO EXPLAIN HOW 9058 05:38:52,768 --> 05:38:53,369 COAGULATION, IMMUNOTHROMBOSIS 9059 05:38:53,369 --> 05:38:55,504 AND EXTRACELLULAR VESICLES 9060 05:38:55,504 --> 05:38:56,939 PROMOTE THE PATHOGENESIS OF 9061 05:38:56,939 --> 05:38:58,040 SEPSIS. 9062 05:38:58,040 --> 05:39:00,743 AND LASTLY, DR. PATRICIA LIAW 9063 05:39:00,743 --> 05:39:03,345 DISCUSSED HOW IMMUNOTHROMBOSIS 9064 05:39:03,345 --> 05:39:05,114 CAN BE THERAPEUTICALLY TARGETED 9065 05:39:05,114 --> 05:39:10,019 IN SEPSIS. 9066 05:39:10,019 --> 05:39:12,855 SO THIS IS THE LESSONS FROM THE 9067 05:39:12,855 --> 05:39:14,089 WORKSHOP. 9068 05:39:14,089 --> 05:39:18,427 SO THE NEW FINDINGS, WE HAD 9069 05:39:18,427 --> 05:39:25,601 SEVERAL NEW FINDINGS OVER -- 9070 05:39:25,601 --> 05:39:28,671 BACTERIAL ROD PROTEINS EPRG 9071 05:39:28,671 --> 05:39:31,407 TRIGGER INFLAMMASOME ACTIVATION 9072 05:39:31,407 --> 05:39:36,178 AND PYROPTOSIS WHICH PROMOTES 9073 05:39:36,178 --> 05:39:39,682 TISSUE FACTOR RELEASE THAT CAN 9074 05:39:39,682 --> 05:39:41,517 LEAD TO INTRAVASCULAR 9075 05:39:41,517 --> 05:39:42,818 COAGULATION IN SEPSIS. 9076 05:39:42,818 --> 05:39:46,121 DR. NIGEL MACKMAN'S FINDINGS AND 9077 05:39:46,121 --> 05:39:48,791 DR. LI'S FINDINGS WERE COMBINED 9078 05:39:48,791 --> 05:39:50,893 TOGETHER TO EXPLAIN THAT OTHER 9079 05:39:50,893 --> 05:39:52,127 INCREASE OF TISSUE FACTOR 9080 05:39:52,127 --> 05:39:55,597 EXPRESSION AND ACTIVITY IN THE 9081 05:39:55,597 --> 05:39:57,066 MICROPHAGES PLAY A SIGNIFICANT 9082 05:39:57,066 --> 05:39:59,301 ROLE IN THE ACTIVATION OF 9083 05:39:59,301 --> 05:40:01,136 COAGULATION IN SEPSIS AND ENDO 9084 05:40:01,136 --> 05:40:02,471 TOXEMIA. 9085 05:40:02,471 --> 05:40:04,707 AND WE DISCUSSED THAT IF YOU 9086 05:40:04,707 --> 05:40:07,409 HEARD THAT OF BLOCKING THE 9087 05:40:07,409 --> 05:40:09,845 INDUCTION OF MONOCYTE TISSUE 9088 05:40:09,845 --> 05:40:11,680 FACTOR EXPRESSION AND RELEASE OF 9089 05:40:11,680 --> 05:40:14,183 TISSUE FACTOR POSITIVE 9090 05:40:14,183 --> 05:40:15,818 EXTRACELLULAR VESICLES OR THE 9091 05:40:15,818 --> 05:40:20,222 ACTIVITY OF TESH EU FACTOR 9092 05:40:20,222 --> 05:40:23,058 EXTRACELLULAR VESICLES MAY 9093 05:40:23,058 --> 05:40:23,992 INTRODUCE INTRAVASCULAR 9094 05:40:23,992 --> 05:40:25,961 COAGULATION IN SEPSIS PATIENTS 9095 05:40:25,961 --> 05:40:28,564 WITHOUT INCREASING THE RISK OF 9096 05:40:28,564 --> 05:40:28,897 BLEEDING. 9097 05:40:28,897 --> 05:40:33,802 AND WE'VE HEARD THAT FROM 9098 05:40:33,802 --> 05:40:37,439 DR. KANDACE THAT NEUTROPHIL 9099 05:40:37,439 --> 05:40:39,441 EXTRACELLULAR THAT TRAPS 9100 05:40:39,441 --> 05:40:42,077 MODIFICATION BY PLATELET FACTOR 9101 05:40:42,077 --> 05:40:44,146 4 CAUSES NETs TO BECOME 9102 05:40:44,146 --> 05:40:47,349 COMPACT AND RESISTANT TO 9103 05:40:47,349 --> 05:40:48,684 NUCLEASE DIGESTION, THAT MAY 9104 05:40:48,684 --> 05:40:51,186 LIMIT THEIR DISSEMINATION AND 9105 05:40:51,186 --> 05:40:52,955 THROMBOTIC POTENTIALS WHEREAS 9106 05:40:52,955 --> 05:40:54,156 ENHANCING THEIR ABILITY TO 9107 05:40:54,156 --> 05:41:04,600 CAPTURE AND KILL BACTERIA. 9108 05:41:05,000 --> 05:41:09,738 WE'VE ALSO -- PAD 4 REGULATES 9109 05:41:09,738 --> 05:41:12,141 SEPSIS PATHOGENESIS BY IMPACTING 9110 05:41:12,141 --> 05:41:13,342 BASELINE INFLAMMATORY RESPONSE 9111 05:41:13,342 --> 05:41:15,978 AND NEUTROPHIL TISSUE, 9112 05:41:15,978 --> 05:41:16,979 INFILTRATION AND COMPOSITION OF 9113 05:41:16,979 --> 05:41:20,215 THE GI MICROBIOMES. 9114 05:41:20,215 --> 05:41:22,084 SO AGAIN WE HEARD THAT SEPSIS 9115 05:41:22,084 --> 05:41:25,020 OUTCOMES IN CECAL SLURRY MODEL 9116 05:41:25,020 --> 05:41:28,423 MAY INFLUENCE BOTH BY 9117 05:41:28,423 --> 05:41:29,625 PAD4 EXPRESSION IN THE CECAL 9118 05:41:29,625 --> 05:41:34,229 SLURRY MODEL DONOR AS WELL AS 9119 05:41:34,229 --> 05:41:37,466 PAD4 EXPRESSION IN RECIPIENT 9120 05:41:37,466 --> 05:41:37,733 SUBJECTS. 9121 05:41:37,733 --> 05:41:40,536 AND AFTER THAT, WE ALSO HAVE 9122 05:41:40,536 --> 05:41:42,738 HEARD FROM DR. LIEW ABOUT 9123 05:41:42,738 --> 05:41:45,974 POTENTIAL FACTORS THAT IMPACT 9124 05:41:45,974 --> 05:41:47,810 EFFICACY OF THERAPEUTIC AGENTS 9125 05:41:47,810 --> 05:41:49,812 IN SEPSIS TREATMENT. 9126 05:41:49,812 --> 05:41:52,648 WE DISCUSSED POTENTIAL FACTORS 9127 05:41:52,648 --> 05:41:56,785 SUCH AS THE TIME OF 9128 05:41:56,785 --> 05:41:59,421 ADMINISTRATION AND ENDORSED 9129 05:41:59,421 --> 05:42:00,722 AGENTS AND TYPES OF 9130 05:42:00,722 --> 05:42:02,057 INTERVENTIONS AND HETEROGENEITY 9131 05:42:02,057 --> 05:42:04,726 IN PATIENTS. 9132 05:42:04,726 --> 05:42:08,096 WE ALSO DISCUSSED ABOUT THE 9133 05:42:08,096 --> 05:42:09,298 ADMINISTRATION TIME FOR 9134 05:42:09,298 --> 05:42:11,266 THERAPEUTICS BY USING THE 9135 05:42:11,266 --> 05:42:14,870 EXAMPLES OF HEPARIN AND THE 9136 05:42:14,870 --> 05:42:16,271 INTERLEUKIN 6 RECEPTOR 9137 05:42:16,271 --> 05:42:18,674 ANTAGONISTS AND THEY MAY BENEFIT 9138 05:42:18,674 --> 05:42:21,410 IF WE ADMINISTER THEM AT THE 9139 05:42:21,410 --> 05:42:23,979 EARLY OR LATE STAGES OF SEPSIS 9140 05:42:23,979 --> 05:42:25,547 RESPECTIVELY. 9141 05:42:25,547 --> 05:42:28,951 SO AS SPEAKERS IN THE WORKSHOP 9142 05:42:28,951 --> 05:42:31,486 DISCUSSED, THE TIME OF THE OTHER 9143 05:42:31,486 --> 05:42:32,754 ADMINISTRATIVE TIME WILL BE 9144 05:42:32,754 --> 05:42:33,956 BENEFICIAL IF WE CAN FIGURE IT 9145 05:42:33,956 --> 05:42:39,628 OUT TO IMPROVE THE OUTCOMES OF 9146 05:42:39,628 --> 05:42:40,295 THERAPEUTICS. 9147 05:42:40,295 --> 05:42:42,998 WE ALSO DISCUSS ABOUT THE 9148 05:42:42,998 --> 05:42:45,534 POTENTIAL OF PRECISION MEDICINE 9149 05:42:45,534 --> 05:42:48,904 OPPORTUNITIES TO IMPROVE USING 9150 05:42:48,904 --> 05:42:51,940 THE GENETIC STRATIFICATION OF 9151 05:42:51,940 --> 05:42:57,279 UNDERLYING RISK. 9152 05:42:57,279 --> 05:43:00,349 FURTHER EXPLAINED ABOUT 9153 05:43:00,349 --> 05:43:01,884 FECAL-INDUCED PERITONITIS MODEL 9154 05:43:01,884 --> 05:43:04,486 OF MURINE SEPSIS AS A SIMPLE AND 9155 05:43:04,486 --> 05:43:06,555 STANDARDIZED EXPERIMENTAL MODEL. 9156 05:43:06,555 --> 05:43:08,624 SO WE ALSO DISCUSSED ABOUT THE 9157 05:43:08,624 --> 05:43:12,527 POTENTIAL THERAPEUTIC AGENTS, 9158 05:43:12,527 --> 05:43:15,264 RECOMBINANT DNASE 1 TO IMPROVE 9159 05:43:15,264 --> 05:43:17,566 OUTCOMES IN SEPSIS. 9160 05:43:17,566 --> 05:43:23,572 IF IT WILL HELP US TO OBTAIN 9161 05:43:23,572 --> 05:43:24,406 BETTER -- PATIENT. 9162 05:43:24,406 --> 05:43:25,874 LASTLY WE DISCUSS ABOUT 9163 05:43:25,874 --> 05:43:27,376 PROGNOSTIC AND PREDICTIVE 9164 05:43:27,376 --> 05:43:31,280 ENRICHMENT STRATEGIES AND THAT 9165 05:43:31,280 --> 05:43:34,483 IT WILL PROFILE A TARGETED 9166 05:43:34,483 --> 05:43:36,418 OPPORTUNITY IN SEPSIS TREATMENT. 9167 05:43:36,418 --> 05:43:40,122 THIS IS OVERALL A VIEW FROM 9168 05:43:40,122 --> 05:43:41,990 PRESENTATIONS FROM OUR SPEAKERS, 9169 05:43:41,990 --> 05:43:45,694 AND THERE WAS ALSO A FEW EXTRA 9170 05:43:45,694 --> 05:43:47,095 POINTS DEVELOPED FROM THE 9171 05:43:47,095 --> 05:43:47,763 QUESTIONS AFTER THE 9172 05:43:47,763 --> 05:43:54,403 PRESENTATION. 9173 05:43:54,403 --> 05:43:55,637 WE DISCUSSED ABOUT TIMING NEEDS 9174 05:43:55,637 --> 05:43:57,039 TO BE CAREFULLY DETERMINED. 9175 05:43:57,039 --> 05:44:00,509 THIS IS ALSO ALIGNED WITH OUR 9176 05:44:00,509 --> 05:44:02,811 SPEAKERS FROM OUR -- FROM THE 9177 05:44:02,811 --> 05:44:04,346 WORKSHOP. 9178 05:44:04,346 --> 05:44:05,747 SO WE ALSO DISCUSSED THAT 9179 05:44:05,747 --> 05:44:09,651 FINDING THE BIOMARKERS THAT CAN 9180 05:44:09,651 --> 05:44:11,086 PROTECT -- DISSEMINATE 9181 05:44:11,086 --> 05:44:12,955 INTERVASCULAR COAGULATION AND 9182 05:44:12,955 --> 05:44:15,123 SEPSIS IS CHALLENGING AT THE 9183 05:44:15,123 --> 05:44:17,292 MOMENT, BUT IT WILL BENEFIT US 9184 05:44:17,292 --> 05:44:19,361 TO DETECT OUR DISEASE AND WE MAY 9185 05:44:19,361 --> 05:44:21,229 BE ABLE TO COME UP WITH THE 9186 05:44:21,229 --> 05:44:25,901 PROPER AND EFFECTIVE STRATEGIES. 9187 05:44:25,901 --> 05:44:27,336 AND THERE WAS ALSO DISCUSSION 9188 05:44:27,336 --> 05:44:31,373 ABOUT EVALUATING THE PROGNOSTIC 9189 05:44:31,373 --> 05:44:33,141 PARAMETERS FOR IMMUNE RESPONSES 9190 05:44:33,141 --> 05:44:36,411 AND WE DISCUSSED THAT IT 9191 05:44:36,411 --> 05:44:38,480 IMPROVED POINT OF CARE FOR OUR 9192 05:44:38,480 --> 05:44:44,152 PATIENTS, AND BECAUSE IT 9193 05:44:44,152 --> 05:44:46,888 REQUIRES A SMALL VOLUME OF BLOOD 9194 05:44:46,888 --> 05:44:47,422 SAMPLES. 9195 05:44:47,422 --> 05:44:49,524 WE DISCUSSED THE ROLE OF 9196 05:44:49,524 --> 05:44:53,562 POTENTIAL FACTORS -- METABOLISM 9197 05:44:53,562 --> 05:44:56,398 THAT CAN POTENTIALLY -- 9198 05:44:56,398 --> 05:44:58,467 INFLAMMATORY RESPONSES. 9199 05:44:58,467 --> 05:44:59,634 SO WE THOUGHT THAT INVESTIGATING 9200 05:44:59,634 --> 05:45:02,137 THESE FACTORS MAY HELP US TO 9201 05:45:02,137 --> 05:45:05,307 BETTER UNDERSTAND THE MECHANISMS 9202 05:45:05,307 --> 05:45:07,275 OF SOME INFLAMMATORY RESPONSES 9203 05:45:07,275 --> 05:45:08,276 FURTHER. 9204 05:45:08,276 --> 05:45:12,948 THIS IS A SUMMARY OF THE SESSION 9205 05:45:12,948 --> 05:45:13,949 TWO. 9206 05:45:13,949 --> 05:45:16,018 I HOPE IT WAS USEFUL FOR OUR 9207 05:45:16,018 --> 05:45:17,119 AUDIENCE TO BETTER UNDERSTAND 9208 05:45:17,119 --> 05:45:20,722 THE MECHANISM UNDERLYING 9209 05:45:20,722 --> 05:45:21,256 INFLAMMATORY RESPONSES IN 9210 05:45:21,256 --> 05:45:21,490 SEPSIS. 9211 05:45:21,490 --> 05:45:31,666 THANK YOU. 9212 05:45:32,701 --> 05:45:35,904 >> THANK YOU, MISUK. 9213 05:45:35,904 --> 05:45:38,573 ANY QUESTIONS FOR THE FIRST TWO 9214 05:45:38,573 --> 05:45:39,508 SESSIONS BEFORE WE MOVE ON TO 9215 05:45:39,508 --> 05:45:43,545 THE THIRD? 9216 05:45:43,545 --> 05:45:44,880 OKAY. 9217 05:45:44,880 --> 05:45:51,353 VINNY AND -- 9218 05:45:51,353 --> 05:45:51,753 >> YEP. 9219 05:45:51,753 --> 05:45:54,356 THANK YOU. 9220 05:45:54,356 --> 05:46:00,495 I'M GOING TO TURN IT OVER TO DRN 9221 05:46:00,495 --> 05:46:01,730 SESSION THREE. 9222 05:46:01,730 --> 05:46:02,130 >> GREAT. 9223 05:46:02,130 --> 05:46:02,864 THANK YOU. 9224 05:46:02,864 --> 05:46:04,499 FIRST OF ALL I WANT TO 9225 05:46:04,499 --> 05:46:07,803 CONGRATULATE EVERYONE FOR THE 9226 05:46:07,803 --> 05:46:09,204 AMAZING TALKS AND THE 9227 05:46:09,204 --> 05:46:10,372 DISCUSSIONS THAT WE'VE HAD. 9228 05:46:10,372 --> 05:46:11,807 IT WAS A VERY INTERESTING DAY, 9229 05:46:11,807 --> 05:46:13,341 AND ALSO FOR OUR SESSION WE 9230 05:46:13,341 --> 05:46:15,911 REALLY ENJOYED HEARING TO ALL 9231 05:46:15,911 --> 05:46:17,379 THE DISCUSSIONS. 9232 05:46:17,379 --> 05:46:20,348 I WANT TO THANK DR. LIU ALSO FOR 9233 05:46:20,348 --> 05:46:21,650 WORKING TOGETHER ON THIS. 9234 05:46:21,650 --> 05:46:25,821 SO WE'RE GOING TO BE PRETTY 9235 05:46:25,821 --> 05:46:26,021 BRIEF. 9236 05:46:26,021 --> 05:46:26,922 ONE OF THE THINGS I WANTED TO 9237 05:46:26,922 --> 05:46:32,194 MENTION IS THAT WE ALL FELT VERY 9238 05:46:32,194 --> 05:46:35,263 OPTIMISTIC AND WE THINK AS 9239 05:46:35,263 --> 05:46:36,665 DR. LIEW JUST MENTIONED TO ME, 9240 05:46:36,665 --> 05:46:37,999 WE ARE VERY HAPPY AND EXCITED 9241 05:46:37,999 --> 05:46:42,104 THAT WE ARE SEPSIS RESEARCHERS 9242 05:46:42,104 --> 05:46:42,771 AT THIS TIME, BECAUSE THE FIELD 9243 05:46:42,771 --> 05:46:44,406 IS PROGRESSING AND THAT'S HOW WE 9244 05:46:44,406 --> 05:46:47,142 WANT TO CLOSE ANYWAY, WITH SOME 9245 05:46:47,142 --> 05:46:48,176 OPTIMISM THAT WE'RE GOING TO BE 9246 05:46:48,176 --> 05:46:57,752 ABLE TO MOVE THE FIELD FORWARD. 9247 05:46:57,752 --> 05:47:01,022 SO IN SUMMARY, WHAT CAN A.I. 9248 05:47:01,022 --> 05:47:02,290 PREDICTIVE ANALYTICS DO AND WHAT 9249 05:47:02,290 --> 05:47:03,859 ARE SOME BARRIERS IN THEIR 9250 05:47:03,859 --> 05:47:04,459 ADOPTION? 9251 05:47:04,459 --> 05:47:09,297 SO WE HEARD FROM OUR SCIENTISTS 9252 05:47:09,297 --> 05:47:10,732 THAT THE PREDICTIVE TOOLS WE 9253 05:47:10,732 --> 05:47:11,500 HAVE ARE PROMISING. 9254 05:47:11,500 --> 05:47:12,801 THEY'RE NOT PERFECT, THERE ARE 9255 05:47:12,801 --> 05:47:15,103 SOME DEFICIENCIES, WE KNOW THAT 9256 05:47:15,103 --> 05:47:16,638 THERE'S STRONG CONCERNS WITH THE 9257 05:47:16,638 --> 05:47:18,273 SEPSIS DEFINITIONS, WITH HOW WE 9258 05:47:18,273 --> 05:47:23,044 USE THE DATA, THE HETEROGENEITY 9259 05:47:23,044 --> 05:47:23,845 OF THE CONDITION ITSELF, WHICH 9260 05:47:23,845 --> 05:47:25,147 CREATES A LOT OF BARRIER, A LOT 9261 05:47:25,147 --> 05:47:28,049 OF PROBLEM, BUT SOME EXAMPLES 9262 05:47:28,049 --> 05:47:28,350 WERE GIVEN. 9263 05:47:28,350 --> 05:47:31,153 YOU CAN SEE HERE ON THE LEFT 9264 05:47:31,153 --> 05:47:35,223 UPPER THAT SOME TOOLS HAVE A 9265 05:47:35,223 --> 05:47:37,826 GOOD PROGNOSTIC ABILITY, GOOD 9266 05:47:37,826 --> 05:47:38,894 SPECIFICITY, GOOD SENSITIVITY, 9267 05:47:38,894 --> 05:47:40,762 AND CAN HELP IN DECREASING 9268 05:47:40,762 --> 05:47:42,964 MORTALITY, BUT ALSO LOOKING INTO 9269 05:47:42,964 --> 05:47:43,732 THE SEQUELAE. 9270 05:47:43,732 --> 05:47:45,133 WE'RE NOT LOOKING ONLY INTO 9271 05:47:45,133 --> 05:47:46,234 SEPSIS MORTALITY. 9272 05:47:46,234 --> 05:47:50,138 THAT ACTUALLY DURING ONE OF OUR 9273 05:47:50,138 --> 05:47:50,739 DISCUSSIONS, IT WAS BROUGHT UP 9274 05:47:50,739 --> 05:47:52,807 EVEN IF WE KNOW ABOUT THE 9275 05:47:52,807 --> 05:47:53,975 INCREASED MORTALITY, WHAT DO WE 9276 05:47:53,975 --> 05:47:56,511 DO ABOUT IT. 9277 05:47:56,511 --> 05:47:58,580 SO WE'RE ALSO LOOKING AT THE 9278 05:47:58,580 --> 05:47:59,548 MORBIDITY IN THE SEQUELAE, WHICH 9279 05:47:59,548 --> 05:48:02,083 IS IMPORTANT. 9280 05:48:02,083 --> 05:48:04,786 A LOT OF HIGH PERFORMANCE 9281 05:48:04,786 --> 05:48:06,421 PREDICTION MODELS FOR NEW ICU 9282 05:48:06,421 --> 05:48:08,823 SEPSIS CAN BE DERIVED FROM A 9283 05:48:08,823 --> 05:48:11,393 COMBINATION OF EHR DATA AND ALSO 9284 05:48:11,393 --> 05:48:13,428 IT WAS MENTIONED THAT THERE ARE 9285 05:48:13,428 --> 05:48:15,297 OTHER MARKERS THAT COULD BE USED 9286 05:48:15,297 --> 05:48:19,234 ALONG WITH EHR DATA LIKE 9287 05:48:19,234 --> 05:48:21,636 METABOLOMICS, LIKE RNA 9288 05:48:21,636 --> 05:48:22,370 SEQUENCING, TRANSCRIPTOMICS AND 9289 05:48:22,370 --> 05:48:25,440 SO FORTH. 9290 05:48:25,440 --> 05:48:26,241 ADDITIONALLY, THERE WERE 9291 05:48:26,241 --> 05:48:28,310 DISCUSSIONS ABOUT THE UTILITY OF 9292 05:48:28,310 --> 05:48:30,512 THE PHENOTYPES, THE SEPSIS 9293 05:48:30,512 --> 05:48:30,812 PHENOTYPES. 9294 05:48:30,812 --> 05:48:33,782 ARE THERE ANY SIMILAR 9295 05:48:33,782 --> 05:48:34,783 CHARACTERISTICS IN SEPTIC 9296 05:48:34,783 --> 05:48:37,752 PATIENTS THAT WE COULD USE TO 9297 05:48:37,752 --> 05:48:39,321 GROUP THEM AND ACTUALLY TAILOR 9298 05:48:39,321 --> 05:48:44,292 THE TREATMENTS OR USE THEM AS -- 9299 05:48:44,292 --> 05:48:45,794 USE THEM FOR THE PROGNOSIS IN 9300 05:48:45,794 --> 05:48:50,765 THE RISK ASSESSMENT OF SEPSIS. 9301 05:48:50,765 --> 05:48:54,035 AND WE KNOW IN MOST CASES WE 9302 05:48:54,035 --> 05:48:56,972 HAVE AN INFLAMMATION-BASED 9303 05:48:56,972 --> 05:48:58,173 SUBTYPES LIKE THE 9304 05:48:58,173 --> 05:48:59,941 HYPERINFLAMMATORY AND 9305 05:48:59,941 --> 05:49:00,709 HYPOINFLAMMATORY SUBTYPES THAT 9306 05:49:00,709 --> 05:49:03,545 COULD BE USEFUL IN TREATMENT AS 9307 05:49:03,545 --> 05:49:06,181 WELL, YOU KNOW THAT 9308 05:49:06,181 --> 05:49:10,418 IMMUNOMODULATORS AND IMMUNE 9309 05:49:10,418 --> 05:49:17,092 TREATMENTS TREATMENTS GIVEN AT T 9310 05:49:17,092 --> 05:49:18,393 TIME MIGHT BE BENEFICIAL BUT WE 9311 05:49:18,393 --> 05:49:21,029 ALSO TALKED ABOUT THE CHALLENGES 9312 05:49:21,029 --> 05:49:26,935 OF THOSE SUBTYPES CHANGING AS 9313 05:49:26,935 --> 05:49:28,136 SEPSIS PROGRESSES AND VARY WITH 9314 05:49:28,136 --> 05:49:28,603 TIME. 9315 05:49:28,603 --> 05:49:30,205 WHAT ARE SOME OF THE BARRIERS 9316 05:49:30,205 --> 05:49:32,173 WITH THE USE OF A.I. AND 9317 05:49:32,173 --> 05:49:33,508 PREDICTIVE ANALYTICS IN SEPSIS. 9318 05:49:33,508 --> 05:49:35,777 THERE'S SOME DISTRUST FROM THE 9319 05:49:35,777 --> 05:49:36,044 PROVIDERS. 9320 05:49:36,044 --> 05:49:37,345 THEY WANT TO MAKE SURE THE 9321 05:49:37,345 --> 05:49:38,647 MODELS ARE EXPLAINABLE, THAT THE 9322 05:49:38,647 --> 05:49:41,583 TIME FRAME IS BELIEVABLE. 9323 05:49:41,583 --> 05:49:44,085 THEY NEED TO BE GENERALIZABLE 9324 05:49:44,085 --> 05:49:44,753 AND THAT CREATES A PROBLEM 9325 05:49:44,753 --> 05:49:48,356 BECAUSE OF THE HETEROGENEITY 9326 05:49:48,356 --> 05:49:51,026 THAT WE JUST DISCUSSED IN THE 9327 05:49:51,026 --> 05:49:52,294 DIFFERENCES IN THE POPULATIONS 9328 05:49:52,294 --> 05:49:53,962 THAT ARE STUDIED. 9329 05:49:53,962 --> 05:49:55,397 THE ALARM FATIGUE, WE'VE SEEN 9330 05:49:55,397 --> 05:49:56,164 THAT MULTIPLE TIMES. 9331 05:49:56,164 --> 05:49:58,900 WHEN PROVIDERS RECEIVE ALERTS 9332 05:49:58,900 --> 05:50:00,869 EVERY TIEF MINUTES ABOUT SEPTIC 9333 05:50:00,869 --> 05:50:02,604 PATIENTS AND IN MANY CASES THESE 9334 05:50:02,604 --> 05:50:13,014 ARE NOT CORRECT, THEN -- 9335 05:50:13,948 --> 05:50:14,649 [INTERRUPTION] 9336 05:50:14,649 --> 05:50:15,950 >> SORRY I'M HEARING SOME 9337 05:50:15,950 --> 05:50:18,253 BACKGROUND NOISE. 9338 05:50:18,253 --> 05:50:19,821 SO WE'VE ALL FACED ALERT FATIGUE 9339 05:50:19,821 --> 05:50:22,324 AND IT'S A PROBLEM THAT REMAINS. 9340 05:50:22,324 --> 05:50:26,561 AND BIAS AS WELL, IS THE DATA 9341 05:50:26,561 --> 05:50:28,763 PROCESSED IN A WAY THAT DOES NOT 9342 05:50:28,763 --> 05:50:33,134 INCREASE BIAS AND ARE THERE 9343 05:50:33,134 --> 05:50:35,737 GROUPS -- SPECIFIC GROUPS, 9344 05:50:35,737 --> 05:50:37,272 AGAIN, DISCRIMINATED AGAINST IF 9345 05:50:37,272 --> 05:50:39,040 THE DATA IS NOT CORRECT AND THEY 9346 05:50:39,040 --> 05:50:39,774 DON'T HAVE ACCESS, THEY DON'T 9347 05:50:39,774 --> 05:50:41,109 HAVE THE RIGHT TREATMENT. 9348 05:50:41,109 --> 05:50:43,745 SO THESE ARE THINGS TO CONSIDER 9349 05:50:43,745 --> 05:50:45,480 WHEN THOSE TOOLS, THE A.I. TOOLS 9350 05:50:45,480 --> 05:50:53,121 ARE DEVELOPED. 9351 05:50:53,121 --> 05:50:58,093 I'M GOING TO CLOSE WITH WHAT WE 9352 05:50:58,093 --> 05:51:02,297 HEARD TODAY FROM DR. BIHORAC 9353 05:51:02,297 --> 05:51:03,164 ABOUT THE A.I. AT HOME A AND IN 9354 05:51:03,164 --> 05:51:06,167 THE HOSPITAL AND HOW MANY 9355 05:51:06,167 --> 05:51:07,135 DIFFERENT APPLICATIONS A.I. CAN 9356 05:51:07,135 --> 05:51:08,837 HAVE FOR PREDICTION, DIAGNOSIS, 9357 05:51:08,837 --> 05:51:10,105 TREATMENT AND RECOVERY, AND 9358 05:51:10,105 --> 05:51:11,439 MONITORING, WHICH IS IMPORTANT, 9359 05:51:11,439 --> 05:51:12,941 AND WHERE DO WE MONITOR THOSE 9360 05:51:12,941 --> 05:51:13,208 PATIENTS? 9361 05:51:13,208 --> 05:51:14,909 DO WE DO IT IN THE HOSPITAL, IN 9362 05:51:14,909 --> 05:51:18,847 THE EMERGENCY ROOM, IN THE ICU, 9363 05:51:18,847 --> 05:51:22,384 IN THE WARDS, OR DO WE EVEN 9364 05:51:22,384 --> 05:51:23,685 START AT HOME FOR SPECIFIC 9365 05:51:23,685 --> 05:51:25,954 PATIENTS. 9366 05:51:25,954 --> 05:51:27,722 AND DEVELOPING DIGITAL TWINS 9367 05:51:27,722 --> 05:51:29,324 LIKE THEY HAVE AT THE UNIVERSITY 9368 05:51:29,324 --> 05:51:32,127 OF FLORIDA, AND WHERE WE CAN 9369 05:51:32,127 --> 05:51:33,962 ACTUALLY TAYLOR SPECIFIC 9370 05:51:33,962 --> 05:51:35,330 TREATMENTS AND LOOK AT SPECIFIC 9371 05:51:35,330 --> 05:51:38,333 CHARACTERISTICS OF THOSE 9372 05:51:38,333 --> 05:51:42,103 PATIENTS IN TERMS OF PAIN OR 9373 05:51:42,103 --> 05:51:43,405 MOVEMENT AND SO FORTH, THIS CAN 9374 05:51:43,405 --> 05:51:46,541 BE REVOLUTIONARY AND HAVING 9375 05:51:46,541 --> 05:51:48,676 THOSE CLINICAL BIAS SENSORS CAN 9376 05:51:48,676 --> 05:51:50,678 MAKE A HUGE DIFFERENCE IN THE 9377 05:51:50,678 --> 05:51:54,516 PREDICTION BUT ALSO IN HAVING -- 9378 05:51:54,516 --> 05:51:55,950 IN TAILORING THOSE TREATMENTS 9379 05:51:55,950 --> 05:51:57,585 FOR THE SPECIFIC PATIENTS. 9380 05:51:57,585 --> 05:51:59,821 THERE ARE MULTIPLE MOBILE APPS 9381 05:51:59,821 --> 05:52:01,189 THAT HAVE BEEN DEVELOPED WITH 9382 05:52:01,189 --> 05:52:05,360 TEXT MESSAGING, LIVE VIDEO 9383 05:52:05,360 --> 05:52:08,196 CALLS, SYNCHRONOUS VIDEO CALLS, 9384 05:52:08,196 --> 05:52:09,931 AND A.I. ASSISTIVE COMMUNICATION 9385 05:52:09,931 --> 05:52:12,100 THAT CAN ALL HELP WITH 9386 05:52:12,100 --> 05:52:15,637 TELEHEALTH AND AGAIN TRYING TO 9387 05:52:15,637 --> 05:52:18,239 DIAGNOSE THOSE PATIENTS AS SOON 9388 05:52:18,239 --> 05:52:20,008 AS -- AS EARLY AS WE CAN, AND 9389 05:52:20,008 --> 05:52:21,743 THEN TAYLOR THOSE TREATMENTS TO 9390 05:52:21,743 --> 05:52:24,712 BE ABLE TO MOVE TOWARDS 9391 05:52:24,712 --> 05:52:28,216 PRECISION MEDICINE. 9392 05:52:28,216 --> 05:52:38,393 THANK YOU. 9393 05:52:39,027 --> 05:52:39,694 >> GREAT. 9394 05:52:39,694 --> 05:52:46,501 THANK YOU, IOANNIS AND VINNY AND 9395 05:52:46,501 --> 05:52:47,902 ALL THE MODERATORS AND CHAIRS, 9396 05:52:47,902 --> 05:52:48,803 THANK YOU FOR PROVIDING A 9397 05:52:48,803 --> 05:52:50,438 SUMMARY OF THE SESSIONS. 9398 05:52:50,438 --> 05:52:53,174 I'M HOPEFUL THAT ALL THE 9399 05:52:53,174 --> 05:52:57,645 AUDIENCE HAD A LOT TO TAKE AWAY 9400 05:52:57,645 --> 05:52:58,947 FROM EACH SESSION AS THE 9401 05:52:58,947 --> 05:53:00,281 SUMMARIES. 9402 05:53:00,281 --> 05:53:02,383 I THINK WE HAVE A FEW MINUTES IF 9403 05:53:02,383 --> 05:53:04,986 ANYBODY HAD ANY LAST-MINUTE 9404 05:53:04,986 --> 05:53:08,490 QUESTIONS FROM EACH OTHER OR 9405 05:53:08,490 --> 05:53:10,124 FROM ANY OF THE PANELISTS OR 9406 05:53:10,124 --> 05:53:11,125 SPEAKERS. 9407 05:53:11,125 --> 05:53:13,094 >> I HAVE A QUESTION. 9408 05:53:13,094 --> 05:53:15,930 SO NOW WE HEARD ABOUT ALL THE 9409 05:53:15,930 --> 05:53:18,433 TALKS, DISCUSSIONS AND WE HAVE 9410 05:53:18,433 --> 05:53:22,070 HEARD OF THE REPORT OUT, SO 9411 05:53:22,070 --> 05:53:22,403 FANTASTIC. 9412 05:53:22,403 --> 05:53:24,172 NOW MY REQUEST TO ALL OF US NOW 9413 05:53:24,172 --> 05:53:26,774 HERE IS THAT IF WE CAN DO ONE 9414 05:53:26,774 --> 05:53:29,277 THING AND ONE THING ONLY, WHAT 9415 05:53:29,277 --> 05:53:31,346 WOULD YOU LIKE US TO DO IN THIS 9416 05:53:31,346 --> 05:53:32,881 CASE TO REALLY ADVANCE THE 9417 05:53:32,881 --> 05:53:33,448 SEPSIS FIELD? 9418 05:53:33,448 --> 05:53:43,291 THANK YOU. 9419 05:53:43,291 --> 05:53:44,926 >> I CAN GO FIRST IF THAT'S 9420 05:53:44,926 --> 05:53:45,793 OKAY. 9421 05:53:45,793 --> 05:53:47,128 I WOULD SAY, YOU KNOW, REGARDING 9422 05:53:47,128 --> 05:53:48,763 UNDERSTANDING MECHANISMS OF 9423 05:53:48,763 --> 05:53:50,098 DISPARITIES IN SEPSIS, ONE OF 9424 05:53:50,098 --> 05:53:51,833 THE MAIN CHALLENGES IS DATA. 9425 05:53:51,833 --> 05:53:54,235 SO WE HAVE ON THE ONE HAND VERY 9426 05:53:54,235 --> 05:53:56,671 LARGE ADMINISTRATIVE DATA THAT 9427 05:53:56,671 --> 05:53:59,340 LACKS GRANULAR VARIABLES RELATED 9428 05:53:59,340 --> 05:54:00,542 TO EQUITY SO WE CAN'T EVEN 9429 05:54:00,542 --> 05:54:01,543 MEASURE AN INDIVIDUAL'S INCOME 9430 05:54:01,543 --> 05:54:03,645 OR WEALTH, FOR EXAMPLE, IN THOSE 9431 05:54:03,645 --> 05:54:04,012 SORTS OF DATA. 9432 05:54:04,012 --> 05:54:05,747 ON THE OTHER HAND, WE HAVE THE 9433 05:54:05,747 --> 05:54:08,016 EHR DATA WHICH ARE VERY DETAILED 9434 05:54:08,016 --> 05:54:09,551 BEEN NOT GENERALIZABLE, SO IT 9435 05:54:09,551 --> 05:54:10,318 STRIKES ME THAT SOMETHING IN THE 9436 05:54:10,318 --> 05:54:12,287 MIDDLE IS NEEDED, LIKE SOME SORT 9437 05:54:12,287 --> 05:54:15,356 OF REGISTRY THAT INCLUDES 9438 05:54:15,356 --> 05:54:19,193 VARIABLES RE VA RELEVANT TO SOCL 9439 05:54:19,193 --> 05:54:20,595 DETERMINANTS OF HEALTH THAT'S 9440 05:54:20,595 --> 05:54:24,966 GRANULAR BUT ALSO HAS THE 9441 05:54:24,966 --> 05:54:34,309 NECESSARY BREADTH. 9442 05:54:34,309 --> 05:54:36,210 >> ONE THING I WOULD ALSO ADD TO 9443 05:54:36,210 --> 05:54:39,881 THAT, THE NIH CAN HELP WITH 9444 05:54:39,881 --> 05:54:42,717 HAVING MORE -- BRINGING ALL THE 9445 05:54:42,717 --> 05:54:44,919 SCIENTISTS TOGETHER, DATA FROM 9446 05:54:44,919 --> 05:54:51,826 SINGLE INSTITUTION OR FROM TWO 9447 05:54:51,826 --> 05:54:53,561 INSTITUTIONS, NOT THAT GREAT. 9448 05:54:53,561 --> 05:54:55,296 URGENCY IN SEPSIS IS THERE, IT'S 9449 05:54:55,296 --> 05:54:56,731 EVIDENT, AND WE NEED TO STUDY 9450 05:54:56,731 --> 05:54:58,166 MULTIPLE DIFFERENT POPULATIONS. 9451 05:54:58,166 --> 05:55:01,235 THERE ARE MANY DIFFERENT 9452 05:55:01,235 --> 05:55:02,770 UNDERLYING CONDITIONS AND 9453 05:55:02,770 --> 05:55:03,538 SOCIOECONOMIC CONDITIONS AS 9454 05:55:03,538 --> 05:55:04,739 WELL, SO WE NEED TO MAKE SURE 9455 05:55:04,739 --> 05:55:07,041 THAT ALL THE STUDIES INCLUDE 9456 05:55:07,041 --> 05:55:09,110 DIFFERENT POPULATIONS, DIVERSE 9457 05:55:09,110 --> 05:55:10,645 POPULATIONS FROM THROUGHOUT THE 9458 05:55:10,645 --> 05:55:13,047 COUNTRY, AND IT WOULD BE GREAT 9459 05:55:13,047 --> 05:55:16,250 TO BRING SCIENTISTS AND SCIENCE 9460 05:55:16,250 --> 05:55:17,785 TOGETHER FOR MULTISITE STUDIES 9461 05:55:17,785 --> 05:55:24,025 TO TACKLE THAT. 9462 05:55:24,025 --> 05:55:24,659 >> AZRA. 9463 05:55:24,659 --> 05:55:26,260 >> FIRST OF ALL I WANT TO THANK 9464 05:55:26,260 --> 05:55:27,762 YOU FOR PUTTING US ALL IN ONE 9465 05:55:27,762 --> 05:55:27,962 ROOM. 9466 05:55:27,962 --> 05:55:29,063 THAT WAS A FANTASTIC WORKSHOP. 9467 05:55:29,063 --> 05:55:31,165 I WANT TO SAY, I'M A PART OF THE 9468 05:55:31,165 --> 05:55:32,400 BRIDGE TO A.I. COMMON FUND. 9469 05:55:32,400 --> 05:55:36,504 ONE OF OUR DATA GENERATION 9470 05:55:36,504 --> 05:55:38,506 PROJECTS IS A CHORUS OF ICU 9471 05:55:38,506 --> 05:55:40,708 COHORTS OF 100,000 PATIENTS FROM 9472 05:55:40,708 --> 05:55:41,776 10 INSTITUTIONS, WITH NOT 9473 05:55:41,776 --> 05:55:43,878 PARTICULAR FOCUS ON SEPSIS, BUT 9474 05:55:43,878 --> 05:55:44,879 WILL INCLUDE SEPSIS. 9475 05:55:44,879 --> 05:55:46,381 BUT IT WILL CREATE A NETWORK I 9476 05:55:46,381 --> 05:55:48,383 THINK THAT CAN GO IN ENRICHMENT, 9477 05:55:48,383 --> 05:55:51,219 BECAUSE WE SPOKE WITH COMMON 9478 05:55:51,219 --> 05:55:52,620 FUND SAYING WE NEED TO ENRICH 9479 05:55:52,620 --> 05:55:53,421 FOR CERTAIN CONDITIONS AND WE 9480 05:55:53,421 --> 05:55:56,691 NEED TO GO DEEPER BIOLOGICAL 9481 05:55:56,691 --> 05:55:57,992 SAMPLING FOR THOSE COHORTS, AND 9482 05:55:57,992 --> 05:55:59,293 I THINK THAT COULD BE 9483 05:55:59,293 --> 05:56:00,094 INTERACTION BETWEEN THE 9484 05:56:00,094 --> 05:56:00,395 INSTITUTES. 9485 05:56:00,395 --> 05:56:04,899 I THINK OF TWO -- IF I WANT TO 9486 05:56:04,899 --> 05:56:06,300 GO MORE GRANULAR DEEPER, I WILL 9487 05:56:06,300 --> 05:56:08,503 GO IN KIDNEY, LUNG AND HEART. 9488 05:56:08,503 --> 05:56:09,604 LIKE IN THE SEPSIS, WE NEED TO 9489 05:56:09,604 --> 05:56:11,572 HAVE A DEEPER BIOLOGICAL 9490 05:56:11,572 --> 05:56:13,241 UNDERSTANDING OF THESE ORGANS' 9491 05:56:13,241 --> 05:56:13,908 ROLE IN THE SEPSIS. 9492 05:56:13,908 --> 05:56:16,177 I GET NIGMS, THEY NEVER WANT TO 9493 05:56:16,177 --> 05:56:17,412 HEAR ABOUT ORGANS. 9494 05:56:17,412 --> 05:56:18,946 I THINK THIS IS A GREAT IDEA TO 9495 05:56:18,946 --> 05:56:20,148 START BUILDING ON WHAT WE HAVE 9496 05:56:20,148 --> 05:56:23,117 ALREADY BUILT WITH COMMON FUND. 9497 05:56:23,117 --> 05:56:28,623 >> VINNY? 9498 05:56:28,623 --> 05:56:30,224 >> I AGREE WITH ALL OF THAT. 9499 05:56:30,224 --> 05:56:31,659 I ALSO THINK WE NEED TO EXPAND 9500 05:56:31,659 --> 05:56:34,195 THE STAKEHOLDERS AND THE SEPSIS 9501 05:56:34,195 --> 05:56:34,495 DISCUSSION. 9502 05:56:34,495 --> 05:56:35,630 IF WE'RE REALLY GOING TO MOVE 9503 05:56:35,630 --> 05:56:37,031 UPSTREAM, WE HAVE TO INCLUDE THE 9504 05:56:37,031 --> 05:56:40,001 DATA SOURCES, THE 9505 05:56:40,001 --> 05:56:41,536 INSTRUMENTATION, AND THE PEOPLE 9506 05:56:41,536 --> 05:56:43,638 WHO WORK IN THOSE ENVIRONMENTS, 9507 05:56:43,638 --> 05:56:46,240 INCLUDING THE PATIENTS. 9508 05:56:46,240 --> 05:56:48,242 SO I KNOW IT'S A LITTLE BIT OF A 9509 05:56:48,242 --> 05:56:50,211 DIVERGENCE, IT CAN BE ALSO VERY 9510 05:56:50,211 --> 05:56:52,013 MESSY AS YOU MOVE UPSTREAM 9511 05:56:52,013 --> 05:56:53,815 BECAUSE PEOPLE -- THERE'S SO 9512 05:56:53,815 --> 05:56:54,816 MANY TRAJECTORIES, BUT WE JUST 9513 05:56:54,816 --> 05:56:59,153 DON'T HAVE INSIGHT AT SCALE, I 9514 05:56:59,153 --> 05:57:02,223 DON'T THINK, TODAY ABOUT WHAT'S 9515 05:57:02,223 --> 05:57:04,659 HAPPENING IN THOSE CONTEXTS, 9516 05:57:04,659 --> 05:57:06,961 ESPECIALLY WHEN WE THINK ABOUT 9517 05:57:06,961 --> 05:57:08,396 DISPARITIES AND COMMUNITY LEVEL 9518 05:57:08,396 --> 05:57:09,864 INPUTS INTO ACUTE SEVERE 9519 05:57:09,864 --> 05:57:10,098 ILLNESS. 9520 05:57:10,098 --> 05:57:12,066 SO I DO THINK WE CAN EXPAND IN 9521 05:57:12,066 --> 05:57:12,567 THAT DOMAIN. 9522 05:57:12,567 --> 05:57:14,135 IT'S GOING TO BE CRITICALLY 9523 05:57:14,135 --> 05:57:14,902 IMPORTANT IF WE'RE GOING TO GET 9524 05:57:14,902 --> 05:57:19,974 TO THE INJURY ITSELF. 9525 05:57:19,974 --> 05:57:21,676 AS EARLY AS WE CAN, EVEN BEFORE 9526 05:57:21,676 --> 05:57:26,114 PATIENTS GET TO THE HOSPITAL. 9527 05:57:26,114 --> 05:57:27,181 >> FANTASTIC. 9528 05:57:27,181 --> 05:57:32,120 ANYTHING ELSE? 9529 05:57:32,120 --> 05:57:34,489 >> I HAVE ONE QUESTION OUT OF 9530 05:57:34,489 --> 05:57:35,790 CURIOSITY BECAUSE WE HAVE SO 9531 05:57:35,790 --> 05:57:37,225 MANY CLINICIANS HERE AS WELL, AS 9532 05:57:37,225 --> 05:57:38,793 WELL AS VINNY FROM KAISER. 9533 05:57:38,793 --> 05:57:43,297 SO HE COULD PROBABLY SPEAK FROM 9534 05:57:43,297 --> 05:57:46,267 THE HEALTH INSURANCE POLICIES 9535 05:57:46,267 --> 05:57:47,001 STANDPOINT. 9536 05:57:47,001 --> 05:57:49,003 MY MOM RECENTLY WAS HOSPITALIZED 9537 05:57:49,003 --> 05:57:50,438 A COUPLE OF YEARS BACK AND SHE 9538 05:57:50,438 --> 05:57:52,974 HAD CANCER, BUT THEN SHE HAD 9539 05:57:52,974 --> 05:57:55,276 INFECTION IN HER BLOOD AND WE 9540 05:57:55,276 --> 05:57:56,511 TOOK HER TO THE HOSPITAL JUST 9541 05:57:56,511 --> 05:57:59,514 BECAUSE OF THAT. 9542 05:57:59,514 --> 05:58:02,316 AND SHE WAS GIVEN A VERY HIGH 9543 05:58:02,316 --> 05:58:04,085 DOSE ANTIBIOTIC, OVERNIGHT SHE 9544 05:58:04,085 --> 05:58:05,286 WENT INTO DELIRIUM AND AFTER A 9545 05:58:05,286 --> 05:58:06,621 FEW WEEKS, SHE PASSED AWAY. 9546 05:58:06,621 --> 05:58:10,224 SO WHEN IT COMES TO 9547 05:58:10,224 --> 05:58:11,192 ACCOUNTABILITY -- AND WHEN SHE 9548 05:58:11,192 --> 05:58:13,094 HAD THE INTERNAL BLEEDING, SHE 9549 05:58:13,094 --> 05:58:15,496 WAS NOT BEING GIVEN BLOOD 9550 05:58:15,496 --> 05:58:17,698 TRANSFUSION UNTIL HER HEMOGLOBIN 9551 05:58:17,698 --> 05:58:19,433 LEVEL WAS FALLING BEYOND A 9552 05:58:19,433 --> 05:58:22,737 CERTAIN THRESHOLD. 9553 05:58:22,737 --> 05:58:24,806 SO IS THAT A STANDARD PRACTICE 9554 05:58:24,806 --> 05:58:27,241 IN SEPSIS ALSO OR IN GENERAL, OR 9555 05:58:27,241 --> 05:58:30,411 WHERE DOES THAT ACCOUNTABILITY 9556 05:58:30,411 --> 05:58:40,855 COME INTO PLACE LIKE THAT? 9557 05:58:41,656 --> 05:58:43,524 >> WELL, I THINK THAT IS, AS WE 9558 05:58:43,524 --> 05:58:44,959 HEARD EARLIER, SOME OF THE PUSH 9559 05:58:44,959 --> 05:58:47,228 THAT'S HAPPENED IN SEPSIS OVER I 9560 05:58:47,228 --> 05:58:48,462 WOULD SAY THE PAST ONE OR TWO 9561 05:58:48,462 --> 05:58:49,931 DECADES, IS TRY TO STANDARDIZE 9562 05:58:49,931 --> 05:58:52,533 PRACTICE, SO THAT WE ARE AT 9563 05:58:52,533 --> 05:58:53,501 LEAST ALIGNING MORE TO 9564 05:58:53,501 --> 05:58:54,735 STANDARDS. 9565 05:58:54,735 --> 05:58:55,770 I THINK WHAT WE'RE FINDING IS 9566 05:58:55,770 --> 05:58:57,505 THAT THE ONE SIZE FITS ALL, YOU 9567 05:58:57,505 --> 05:58:59,340 KNOW, THAT AT THIS THRESHOLD OR 9568 05:58:59,340 --> 05:59:00,541 THAT THRESHOLD, WE SHOULD DO 9569 05:59:00,541 --> 05:59:02,743 THIS OR THAT, FLUIDS, BLOOD 9570 05:59:02,743 --> 05:59:03,477 TRANSFUSION, ANTIBIOTICS, ET 9571 05:59:03,477 --> 05:59:05,246 CETERA. 9572 05:59:05,246 --> 05:59:08,549 SO I WOULD SAY, THERE'S BEEN A 9573 05:59:08,549 --> 05:59:10,117 LARGE PUSH TOWARDS STAND DAITION 9574 05:59:10,117 --> 05:59:11,285 IN ORDER TO DELIVER TIMELY AND 9575 05:59:11,285 --> 05:59:12,520 EFFECTIVE CARE, AND NOW WE'RE IN 9576 05:59:12,520 --> 05:59:16,090 THAT DOMAIN OF PRECISION, WHICH 9577 05:59:16,090 --> 05:59:20,194 IS THAT WE REALLY HAVE TO 9578 05:59:20,194 --> 05:59:21,696 INDIVIDUALIZE CARE, AND ONCE 9579 05:59:21,696 --> 05:59:22,997 WE'VE GOTTEN KIND OF THE RISING 9580 05:59:22,997 --> 05:59:24,999 TIDE TO LIFT ALL BOATS IN TERMS 9581 05:59:24,999 --> 05:59:28,069 OF OUR EARLY DETECTION AND 9582 05:59:28,069 --> 05:59:30,905 AGGRESSIVE INTERVENTIONS, NOW 9583 05:59:30,905 --> 05:59:32,773 LIKE WE'RE REALIZING THOSE ARE 9584 05:59:32,773 --> 05:59:35,543 INSUFFICIENT. 9585 05:59:35,543 --> 05:59:36,277 SO NOT KNOWING TOO MUCH ABOUT 9586 05:59:36,277 --> 05:59:37,378 THE PERSONAL OR INDIVIDUAL 9587 05:59:37,378 --> 05:59:42,316 DETAILS THERE, IT'S ALWAYS A 9588 05:59:42,316 --> 05:59:43,784 TENSION TO TRY TO STAY WITHIN 9589 05:59:43,784 --> 05:59:45,519 LARGER GUIDELINES, BUT 9590 05:59:45,519 --> 05:59:46,487 INDIVIDUALIZE THE CARE BASED ON 9591 05:59:46,487 --> 05:59:48,155 WHAT'S HAPPENING IN FRONT OF YOU 9592 05:59:48,155 --> 05:59:50,625 AT THE BEDSIDE. 9593 05:59:50,625 --> 05:59:55,963 >> DEEP, GO AHEAD. 9594 05:59:55,963 --> 05:59:59,233 >> I'M SO SORRY THAT THAT 9595 05:59:59,233 --> 06:00:00,434 HAPPENED WITH YOUR MOM FIRST OF 9596 06:00:00,434 --> 06:00:00,668 ALL. 9597 06:00:00,668 --> 06:00:02,837 SECONDLY, I WOULD SAY YES, 9598 06:00:02,837 --> 06:00:03,738 ACCOUNTABILITY IS HELPFUL. 9599 06:00:03,738 --> 06:00:05,907 IT REALLY MATTERS HOW WE HOLD 9600 06:00:05,907 --> 06:00:07,675 HOSPITALS ACCOUNTABLE TO THE 9601 06:00:07,675 --> 06:00:09,410 CURRENT SYSTEM, WE PENALIZE 9602 06:00:09,410 --> 06:00:13,648 HOSPITALS FOR NOT MEETING 9603 06:00:13,648 --> 06:00:15,116 CERTAIN QUALITY METRICS, AND 9604 06:00:15,116 --> 06:00:20,087 RELEVANT TO DISPARITY, ONE THAT 9605 06:00:20,087 --> 06:00:21,522 HAS BEEN SHOWN IS THAT LOWER 9606 06:00:21,522 --> 06:00:23,190 RESOURCE HOSPITALS ARE MUCH LESS 9607 06:00:23,190 --> 06:00:24,592 LAKELY TO CONSISTENTLY MEET 9608 06:00:24,592 --> 06:00:25,293 THOSE QUALITY METRICS BECAUSE 9609 06:00:25,293 --> 06:00:27,828 THEY HAVE FEWER RESOURCES TO 9610 06:00:27,828 --> 06:00:29,797 INVEST IN AIR-TIGHT CARE 9611 06:00:29,797 --> 06:00:31,432 PROCESSES, AND THEN THEY GET 9612 06:00:31,432 --> 06:00:32,533 PENALIZED AND THEN THEY HAVE 9613 06:00:32,533 --> 06:00:34,302 FEWER RESOURCES. 9614 06:00:34,302 --> 06:00:36,070 SO IT'S THIS VICIOUS CYCLE. 9615 06:00:36,070 --> 06:00:39,040 AND I WONDER IF THERE IS A WAY 9616 06:00:39,040 --> 06:00:41,142 INSTEAD TO REWARD HOSPITALS THAT 9617 06:00:41,142 --> 06:00:43,544 DO A GOOD JOB RATHER THAN 9618 06:00:43,544 --> 06:00:45,012 INSTITUTE PENALTIES. 9619 06:00:45,012 --> 06:00:46,814 THAT WOULD BE ONE IDEA. 9620 06:00:46,814 --> 06:00:50,551 THE OTHER IDEA IS THAT WE DIDN'T 9621 06:00:50,551 --> 06:00:53,421 GET TO TALK MUCH WHEN JOHN 9622 06:00:53,421 --> 06:00:54,622 DONELY WAS HERE BUT I WAS 9623 06:00:54,622 --> 06:00:56,157 CURIOUS TO ASK HIM ABOUT THE 9624 06:00:56,157 --> 06:00:58,793 MICHIGAN HOSPITAL MED SIB SAFETY 9625 06:00:58,793 --> 06:00:59,894 CONSORTIUM IN MICHIGAN BECAUSE I 9626 06:00:59,894 --> 06:01:01,762 THINK THEY HAVE -- BLUE CROSS IS 9627 06:01:01,762 --> 06:01:03,597 A RELATIVE MONOPOLY IN THE STATE 9628 06:01:03,597 --> 06:01:06,033 OF MICHIGAN AND THEY'RE ABLE TOO 9629 06:01:06,033 --> 06:01:06,667 INCENTIVIZE GROUPS OF HOSPITALS 9630 06:01:06,667 --> 06:01:08,536 TO MEET QUALITY METRICS, SO IT'S 9631 06:01:08,536 --> 06:01:10,604 NOT THAT THE VERY WELL RESOURCED 9632 06:01:10,604 --> 06:01:11,872 UNIVERSITY OF MICHIGAN ALWAYS 9633 06:01:11,872 --> 06:01:12,974 DOES A GOOD JOB, BUT THEY ALSO 9634 06:01:12,974 --> 06:01:17,244 HAVE TO BE RESPONSIBLE FOR OTHER 9635 06:01:17,244 --> 06:01:17,912 HOSPITALS IN THEIR COMMUNITY SO 9636 06:01:17,912 --> 06:01:19,580 THEY'RE REWARDED BASED ON 9637 06:01:19,580 --> 06:01:21,115 AGGREGATE OUTCOMES FOR AN ENTIRE 9638 06:01:21,115 --> 06:01:21,749 REGION. 9639 06:01:21,749 --> 06:01:23,751 AND I THINK THAT'S JUST A GREAT 9640 06:01:23,751 --> 06:01:25,286 MODEL BECAUSE THEN HOSPITALS 9641 06:01:25,286 --> 06:01:27,254 SHARE BEST PRACTICES BETWEEN 9642 06:01:27,254 --> 06:01:30,791 EACH OTHER AND I THINK THOSE ARE 9643 06:01:30,791 --> 06:01:31,892 REALLY TWO MODELS WE NEED TO 9644 06:01:31,892 --> 06:01:34,161 WORK TOWARDS, MAIBL POTENTIALLY 9645 06:01:34,161 --> 06:01:35,696 INSTEAD OF PENALIZING REWARDING 9646 06:01:35,696 --> 06:01:37,164 AND THEN ENCOURAGING HOSPITALS 9647 06:01:37,164 --> 06:01:40,801 TO WORK COLLABORATIVELY. 9648 06:01:40,801 --> 06:01:42,203 >> THAT'S GREAT MODEL. 9649 06:01:42,203 --> 06:01:44,305 THANKS FOR SHARING. 9650 06:01:44,305 --> 06:01:49,610 PATRICIA. 9651 06:01:49,610 --> 06:01:51,746 >> I JUST WANTED TO ADD FROM THE 9652 06:01:51,746 --> 06:01:52,880 BASIC SCIENCE PERSPECTIVE, I 9653 06:01:52,880 --> 06:01:55,449 THINK IT WOULD BE GREAT TO 9654 06:01:55,449 --> 06:01:57,585 ENCOURAGE A BIDIRECTIONAL LINK 9655 06:01:57,585 --> 06:01:59,854 BETWEEN THE BASIC RESEARCHERS 9656 06:01:59,854 --> 06:02:04,291 AND THE CLINICIANS, AND FOR 9657 06:02:04,291 --> 06:02:05,593 TRANSLATIONAL STUDIES IN THE 9658 06:02:05,593 --> 06:02:09,830 FIELD OF SEPSIS, THERE ARE, I 9659 06:02:09,830 --> 06:02:12,700 THINK, MISSED OPPORTUNITIES TO 9660 06:02:12,700 --> 06:02:14,869 COLLECT BIOLOGICAL SPECIMENS AND 9661 06:02:14,869 --> 06:02:16,070 OFTEN WHEN THEY'RE COLLECTED, 9662 06:02:16,070 --> 06:02:17,505 THEY'RE COLLECTED AT A SINGLE 9663 06:02:17,505 --> 06:02:18,072 TIME POINT. 9664 06:02:18,072 --> 06:02:20,241 SO AT ICU ADMISSION. 9665 06:02:20,241 --> 06:02:23,411 BUT BEING ABLE TO BETTER 9666 06:02:23,411 --> 06:02:25,479 UNDERSTAND THE TEMPORAL CHANGES 9667 06:02:25,479 --> 06:02:28,916 THAT HAPPENS IN THE IMMUNE 9668 06:02:28,916 --> 06:02:32,319 SYSTEM AS A PATIENT RECOVERS OR 9669 06:02:32,319 --> 06:02:34,188 DOES NOT, I THINK THERE'S A LOT 9670 06:02:34,188 --> 06:02:36,490 OF VALUE IN THAT, AND BEING ABLE 9671 06:02:36,490 --> 06:02:38,926 TO LINK THE CLINICAL DATA WITH 9672 06:02:38,926 --> 06:02:42,530 THE BIOLOGICAL DATA WOULD BE I 9673 06:02:42,530 --> 06:02:47,101 THINK, A HUGE IMPROVEMENT IN THE 9674 06:02:47,101 --> 06:02:49,737 WAY THAT WE UNDERSTAND SEPSIS 9675 06:02:49,737 --> 06:02:52,139 PATHOPHYSIOLOGY. 9676 06:02:52,139 --> 06:02:53,641 >> THANK YOU, PATRICIA. 9677 06:02:53,641 --> 06:02:55,242 SO I REMEMBER YOU MENTIONED 9678 06:02:55,242 --> 06:02:59,780 WHETHER U.S. HAS A SEPSIS CANADA 9679 06:02:59,780 --> 06:03:02,316 LIKE CONSORTIUM. 9680 06:03:02,316 --> 06:03:05,152 SO LAST YEAR'S STUDY, THE APS 9681 06:03:05,152 --> 06:03:08,489 CONSORTIUM PARTICULARLY 9682 06:03:08,489 --> 06:03:12,093 MENTIONED THE -- APS CONSORTIUM 9683 06:03:12,093 --> 06:03:13,094 COLLECTING MULTIPLE TIME POINTS, 9684 06:03:13,094 --> 06:03:14,628 THAT'S WHAT WE ARE TRYING TO DO, 9685 06:03:14,628 --> 06:03:16,697 BUT IT'S ALSO LIKE ALL OF US 9686 06:03:16,697 --> 06:03:18,699 DISCUSSED TODAY, IT'S VERY 9687 06:03:18,699 --> 06:03:20,668 CHALLENGING. 9688 06:03:20,668 --> 06:03:21,869 BUT -- SO WE ARE WORKING ON 9689 06:03:21,869 --> 06:03:22,103 THAT. 9690 06:03:22,103 --> 06:03:23,838 ALL RIGHT, IT'S ALMOST ON TOP OF 9691 06:03:23,838 --> 06:03:24,271 HOUR. 9692 06:03:24,271 --> 06:03:26,273 I WOULD LIKE TO TAKE THIS 9693 06:03:26,273 --> 06:03:28,576 OPPORTUNITY TO THANK YOU ALL. 9694 06:03:28,576 --> 06:03:30,244 IT HAS BEEN A WONDERFUL DAY. 9695 06:03:30,244 --> 06:03:32,179 IT IS LONG BUT IT'S A WONDER -- 9696 06:03:32,179 --> 06:03:33,881 A LOT OF INFORMATION, A LOT OF 9697 06:03:33,881 --> 06:03:37,985 IDEAS, CONCEPTS, NEW IDEAS 9698 06:03:37,985 --> 06:03:38,552 COMING OUT. 9699 06:03:38,552 --> 06:03:39,854 I THINK THE DISCUSSION WAS 9700 06:03:39,854 --> 06:03:40,187 FANTASTIC. 9701 06:03:40,187 --> 06:03:43,357 I WANT TO SEND EACH OF YOU, OUR 9702 06:03:43,357 --> 06:03:45,993 SPEAKERS, MODERATORS, CHAIRS AND 9703 06:03:45,993 --> 06:03:47,428 ATTENDEES, AND I WANT TO ALSO 9704 06:03:47,428 --> 06:03:50,064 GIVE A BIG SHOUT OUT FOR OUR AV 9705 06:03:50,064 --> 06:03:55,903 TEAMS AND WORKSHOP -- NHLBI 9706 06:03:55,903 --> 06:03:57,304 WORKSHOP THAT HAVE BEEN WORKING 9707 06:03:57,304 --> 06:03:58,439 WITH US FROM THE VERY BEGINNING 9708 06:03:58,439 --> 06:04:01,675 FROM THE GRAPHIC DESIGN, THE AV 9709 06:04:01,675 --> 06:04:02,476 AND ALL THE LOGISTICS OF 9710 06:04:02,476 --> 06:04:03,244 PLANNING. 9711 06:04:03,244 --> 06:04:04,345 JOSHUA HAS BEEN LEADING THAT 9712 06:04:04,345 --> 06:04:06,247 EFFORT SO I WANT A BIG SHOUT OUT 9713 06:04:06,247 --> 06:04:07,148 FOR HIM AS WELL. 9714 06:04:07,148 --> 06:04:11,051 SO REGARDING FOR NEXT STEPS, OUR 9715 06:04:11,051 --> 06:04:12,253 WORKSHOP IS CLOSE TO END, BUT 9716 06:04:12,253 --> 06:04:13,454 OUR JOB IS NOT DONE YET. 9717 06:04:13,454 --> 06:04:15,356 SO FOR SPEAKER, MODERATORS AND 9718 06:04:15,356 --> 06:04:18,359 CHAIRS, WE WILL REACH OUT LATER 9719 06:04:18,359 --> 06:04:20,094 FOR A WHITE PAPER. 9720 06:04:20,094 --> 06:04:23,264 SO FOR THE FUTURE DEVELOPMENTS, 9721 06:04:23,264 --> 06:04:27,201 SO AS WE ALL DISCUSSED, SO 9722 06:04:27,201 --> 06:04:33,741 THE -- SEPSIS -- THE -- IS GOING 9723 06:04:33,741 --> 06:04:35,676 TO BE A LONG JOURNEY, A 9724 06:04:35,676 --> 06:04:36,877 CHALLENGING JOURNEY, ALTHOUGH 9725 06:04:36,877 --> 06:04:39,313 EVERYBODY EXPRESSED SOME 9726 06:04:39,313 --> 06:04:40,080 OPTIMISM, BUT I DON'T THINK 9727 06:04:40,080 --> 06:04:42,316 ANYBODY IS GOING TO LOSE THEIR 9728 06:04:42,316 --> 06:04:42,917 JOB ANYTIME SOON. 9729 06:04:42,917 --> 06:04:44,485 SO WE'RE STILL GOING TO BE 9730 06:04:44,485 --> 06:04:45,386 WORKING ON THAT, AND WE ARE HERE 9731 06:04:45,386 --> 06:04:47,421 TO HELP YOU IN ANY WAY WE CAN TO 9732 06:04:47,421 --> 06:04:49,924 HELP ADVANCE THE FIELD, TO HELP 9733 06:04:49,924 --> 06:04:50,257 OUR PATIENTS. 9734 06:04:50,257 --> 06:04:51,892 SO ANY TIME IF YOU HAVE ANY 9735 06:04:51,892 --> 06:04:54,495 THOUGHTS, IDEAS, REACH OUT TO 9736 06:04:54,495 --> 06:04:56,397 US, SO SEPSIS IS A BIG TOPIC. 9737 06:04:56,397 --> 06:04:59,900 IT'S NOT LIMITED TO BLOOD 9738 06:04:59,900 --> 06:05:01,135 DIVISION, IT'S ALSO A BIG 9739 06:05:01,135 --> 06:05:02,136 PORTFOLIO IN THE LUNG DIVISION, 9740 06:05:02,136 --> 06:05:03,604 IN THE HEART DIVISION, AS MANY 9741 06:05:03,604 --> 06:05:07,274 OF YOU MENTIONED ABOUT KIDNEY AS 9742 06:05:07,274 --> 06:05:10,110 WELL, SO ANYTHING YOU THINK THAT 9743 06:05:10,110 --> 06:05:12,179 WILL HELP US HELP THE PATIENT, 9744 06:05:12,179 --> 06:05:12,913 PLEASE REACH OUT TO US. 9745 06:05:12,913 --> 06:05:15,749 WE ARE HERE TO HELP YOU, TO HELP 9746 06:05:15,749 --> 06:05:16,283 OUR PATIENTS. 9747 06:05:16,283 --> 06:05:21,121 SO WITH THAT, I WANT TO GIVE THE 9748 06:05:21,121 --> 06:05:22,856 FINAL THANK YOU TO YOU ALL, AND 9749 06:05:22,856 --> 06:05:24,291 CLOSE OUT OF THE SESSION. 9750 06:05:24,291 --> 06:05:26,293 SO NOW THE WORKSHOP IS 9751 06:05:26,293 --> 06:05:26,894 ADJOURNED. 9752 06:05:26,894 --> 06:05:27,561 THANK YOU. 9753 06:05:27,561 --> 06:05:29,630 >> CAN I -- CAN I ALSO SAY 9754 06:05:29,630 --> 06:05:29,897 SOMETHING? 9755 06:05:29,897 --> 06:05:32,833 >> SURE. 9756 06:05:32,833 --> 06:05:35,469 >> ONE OF THE FOCUS AREAS OF 9757 06:05:35,469 --> 06:05:37,871 THIS WORKSHOP -- ONE OF THE 9758 06:05:37,871 --> 06:05:39,406 OBJECTIVES OF THIS WORKSHOP WAS 9759 06:05:39,406 --> 06:05:42,042 TO FOSTER COLLABORATIONS, SO IF 9760 06:05:42,042 --> 06:05:45,379 ANY OF YOU START A NEW 9761 06:05:45,379 --> 06:05:47,014 COLLABORATION OR IF YOU FEEL 9762 06:05:47,014 --> 06:05:49,083 THAT IT REALLY HELPED YOU IN 9763 06:05:49,083 --> 06:05:52,286 FINDING NEW PROJECTS TOGETHER 9764 06:05:52,286 --> 06:05:54,388 AFTER LEARNING NEW THINGS, 9765 06:05:54,388 --> 06:05:56,657 PLEASE LET US KNOW LATER. 9766 06:05:56,657 --> 06:06:07,067 THANK YOU ALL VERY MUCH.