1 00:00:05,760 --> 00:00:08,600 >> GOOD MORNING, 2 00:00:08,600 --> 00:00:11,080 AFTERNOON, WHEREVER YOU ARE, I 3 00:00:11,080 --> 00:00:12,480 AM THRILLED TO SEE YOU ALL 4 00:00:12,480 --> 00:00:13,320 HERE TODAY. 5 00:00:13,320 --> 00:00:16,040 I WANT TO THANK YOU ALL FOR 6 00:00:16,040 --> 00:00:18,440 YOUR TREMENDOUS HEALTH AND TO 7 00:00:18,440 --> 00:00:20,720 MAKE THIS WORKSHOP HAPPEN. 8 00:00:20,720 --> 00:00:31,240 PLEASE JOIN ME TO WELCOME 9 00:00:33,200 --> 00:00:34,000 Dr. PATUTE-BELLO. 10 00:00:34,000 --> 00:00:36,680 PLEASE JOIN ME TO GIVE OPENING 11 00:00:36,680 --> 00:00:37,800 REMARKS. 12 00:00:37,800 --> 00:00:38,240 GUS? 13 00:00:38,240 --> 00:00:39,640 >>THANKS, GOOD MORNING OR 14 00:00:39,640 --> 00:00:41,520 AFTERNOON, ON BEHALF OF THE 15 00:00:41,520 --> 00:00:49,640 DIVISION OF LUNG DISEASE AT 16 00:00:49,640 --> 00:00:51,520 NHLBI, IT IS REALLY A GREAT 17 00:00:51,520 --> 00:00:54,360 PLEASURE TO WELCOME YOU ALL 18 00:00:54,360 --> 00:00:57,960 TODAY TO THIS SYMPOSIUM ON 19 00:00:57,960 --> 00:01:00,640 BRAIN AND MUSCLE DYSFUNCTION 20 00:01:00,640 --> 00:01:01,160 IN ARDS SURVIVORS. 21 00:01:01,160 --> 00:01:02,680 I DON'T THINK I NEED TO 22 00:01:02,680 --> 00:01:07,880 EMPHASIZE TO THIS AUDIENCE 23 00:01:07,880 --> 00:01:09,480 THAT ACUTE RESPIRATORY 24 00:01:09,480 --> 00:01:12,440 SYNDROME OR ARDS REMAINS A 25 00:01:12,440 --> 00:01:13,480 DEVASTATING CLINICAL SYNDROME 26 00:01:13,480 --> 00:01:15,560 THAT LEADS TO ACUTE 27 00:01:15,560 --> 00:01:17,360 RESPIRATORY FAILURE AND DEATH 28 00:01:17,360 --> 00:01:19,240 MORE OFTEN THAN WE WOULD LIKE. 29 00:01:19,240 --> 00:01:23,080 FORTUNATELY IN THE LAST FIVE 30 00:01:23,080 --> 00:01:26,040 DECADES, A CONCERTED 31 00:01:26,040 --> 00:01:27,640 EVIDENCE-BASED EFFORT IN 32 00:01:27,640 --> 00:01:29,000 IMPROVING GENERAL CLINICAL 33 00:01:29,000 --> 00:01:29,960 CARE AND VENTILATOR MANAGEMENT 34 00:01:29,960 --> 00:01:33,800 HAS LED TO SIGNIFICANT 35 00:01:33,800 --> 00:01:36,480 REDUCTIONS IN MORTALITY FROM 36 00:01:36,480 --> 00:01:37,600 ABOUT 60 TO 80 PERCENT. 37 00:01:37,600 --> 00:01:41,680 WHEN I STARTED AS A FELLOW, TO 38 00:01:41,680 --> 00:01:46,120 THE CURRENT RATE OF 25 TO 39 00:01:46,120 --> 00:01:46,520 40 PERCENT. 40 00:01:46,520 --> 00:01:48,680 HOWEVER, THERE IS ALSO A 41 00:01:48,680 --> 00:01:50,480 GROWING NUMBER OF ARDS 42 00:01:50,480 --> 00:01:51,480 SURVIVORS AND VERY 43 00:01:51,480 --> 00:01:56,240 UNFORTUNATE, WE ARE SEEING 44 00:01:56,240 --> 00:02:00,000 THESE PATIENTS SUFFER FROM 45 00:02:00,000 --> 00:02:03,320 LASTING SEQUELAE AND THIS 46 00:02:03,320 --> 00:02:06,240 INCLUDES INCREASED MORTALITY, 47 00:02:06,240 --> 00:02:08,200 PHYSICAL, COGNITIVE AND 48 00:02:08,200 --> 00:02:12,640 PERMANENT AND REDUCED QUALITY 49 00:02:12,640 --> 00:02:13,320 OF LIFE. 50 00:02:13,320 --> 00:02:16,840 THESE END WHEN THE PATIENT IS 51 00:02:16,840 --> 00:02:17,200 INTUBATED. 52 00:02:17,200 --> 00:02:18,320 IN FACT, MUSCLE SYSTEMS ARE 53 00:02:18,320 --> 00:02:22,320 SOME OF THE MAIN TARGETS OF 54 00:02:22,320 --> 00:02:22,680 SURVIVORS. 55 00:02:22,680 --> 00:02:26,760 IT HAS A VERY HIGH LEVEL 56 00:02:26,760 --> 00:02:31,080 PREVALENCE OF COGNITIVE 57 00:02:31,080 --> 00:02:32,080 IMPROVEMENT. 58 00:02:32,080 --> 00:02:34,720 70 TO 80 PERCENT OF HOT 59 00:02:34,720 --> 00:02:36,880 DISCHARGED IN ONE YEAR AND 60 00:02:36,880 --> 00:02:39,280 REMAINS UP TO 40 PERCENT FIVE 61 00:02:39,280 --> 00:02:42,000 YEARS AND CLINICAL 62 00:02:42,000 --> 00:02:44,840 EFFECTIVENESS, SKELETAL MUSCLE 63 00:02:44,840 --> 00:02:47,560 WEAKNESS OCCURS IN UP TO 64 00:02:47,560 --> 00:02:49,160 10 PERCENT -- 670 PERCENT OF 65 00:02:49,160 --> 00:02:50,960 ALL CLINICAL PATIENTS AND 66 00:02:50,960 --> 00:02:52,800 THERE ARE SUBSTANTIAL 67 00:02:52,800 --> 00:02:54,320 LONG-TERM IMPAIRMENTS IN 68 00:02:54,320 --> 00:02:56,040 MUSCLE STRENGTH, WALKING 69 00:02:56,040 --> 00:02:57,400 CAPACITY, FISCAL ACTIVITY 70 00:02:57,400 --> 00:03:01,120 BETWEEN SIX MONDAYS ASK EVEN 71 00:03:01,120 --> 00:03:03,320 TWO YEARS AFTER BEING 72 00:03:03,320 --> 00:03:05,400 DISCHARGED FROM THE ICU. 73 00:03:05,400 --> 00:03:09,160 MORE IMPORTANTLY PATIENTS WITH 74 00:03:09,160 --> 00:03:12,080 COVID-19 PNEUMONIA HAVE HIGH 75 00:03:12,080 --> 00:03:13,960 INCIDENCE OF ARDS, UP TO 76 00:03:13,960 --> 00:03:15,000 42 PERCENT OF THESE PATIENTS 77 00:03:15,000 --> 00:03:20,240 AND THE SURVIVORS FROM 78 00:03:20,240 --> 00:03:23,800 COVID-19 ARDS ALSO DEVELOP 79 00:03:23,800 --> 00:03:28,240 MUSCLE WEAKNESS, 35.7 PERCENT, 80 00:03:28,240 --> 00:03:29,000 COGNITIVE IMPAIRMENT UP 81 00:03:29,000 --> 00:03:32,720 17.1 PERCENT SO IT IS VERY 82 00:03:32,720 --> 00:03:34,480 CLEAR THERE IS AN ON GOING 83 00:03:34,480 --> 00:03:36,520 NEED IN THE CLINICAL 84 00:03:36,520 --> 00:03:44,320 MANAGEMENT OF ARDS SURVIVORS 85 00:03:44,320 --> 00:03:45,760 AND URGENCY FOR INTERVENTION 86 00:03:45,760 --> 00:03:48,440 STRATEGIES FOR THESE PATIENTS. 87 00:03:48,440 --> 00:03:52,720 THERE IS EMERGING DATA THAT 88 00:03:52,720 --> 00:03:54,880 SHOWS WEIGHT AND MUSCLE 89 00:03:54,880 --> 00:03:56,720 WEAKNESS CONTRIBUTE TO BRAIN 90 00:03:56,720 --> 00:04:03,600 AND MUSCLE DISFUNCTIONS WE SEE 91 00:04:03,600 --> 00:04:07,280 IN ARDS SURVIVORS ALTHOUGH THE 92 00:04:07,280 --> 00:04:10,200 MECHANISMS THAT UNDER LIE 93 00:04:10,200 --> 00:04:11,920 THESE ARE NOT KNOWN SO THERE 94 00:04:11,920 --> 00:04:14,360 IS A CRITICAL GAP IN PART OF 95 00:04:14,360 --> 00:04:15,400 THE PHYSIOLOGY OF THIS AREA 96 00:04:15,400 --> 00:04:17,960 AND HERE IS WHERE THIS 97 00:04:17,960 --> 00:04:20,160 WORKSHOP COMES IN. 98 00:04:20,160 --> 00:04:22,720 SO NHLBI HAS CONVENED THIS 99 00:04:22,720 --> 00:04:25,480 WORKSHOP WITH PANEL EXPERTS, 100 00:04:25,480 --> 00:04:28,280 ALL OF YOU, TO SPEAK FROM THE 101 00:04:28,280 --> 00:04:30,240 RESEARCH COMMUNITY AND KEY 102 00:04:30,240 --> 00:04:30,680 STAKEHOLDERS. 103 00:04:30,680 --> 00:04:32,440 THIS IS QUIETNESS AND TIMELY. 104 00:04:32,440 --> 00:04:35,960 AND WE HOPE THAT THIS WORKSHOP 105 00:04:35,960 --> 00:04:37,800 WILL CAPTURE THE STATE OF 106 00:04:37,800 --> 00:04:41,640 SCIENCE AS IT RELATES TO BRAIN 107 00:04:41,640 --> 00:04:43,320 AND MUSCLE DYSFUNCTION 108 00:04:43,320 --> 00:04:45,240 FOLLOWING ARDS AND CRITICAL 109 00:04:45,240 --> 00:04:45,560 ILLNESS. 110 00:04:45,560 --> 00:04:48,960 WE ALSO HOPE THAT YOU WILL 111 00:04:48,960 --> 00:04:51,200 HELP US EVALUATE CRITICAL 112 00:04:51,200 --> 00:04:52,400 KNOWLEDGE GAPS AND KEY 113 00:04:52,400 --> 00:04:57,200 BARRIERS IN THIS FIELD AND 114 00:04:57,200 --> 00:04:58,880 IDENTIFY RESEARCH 115 00:04:58,880 --> 00:05:00,680 OPPORTUNITIES IN UNDERSTANDING 116 00:05:00,680 --> 00:05:03,320 THE PATH OF ETIOLOGY OF BRAIN 117 00:05:03,320 --> 00:05:05,280 AND MUSCLE DYSFUNCTION IN 118 00:05:05,280 --> 00:05:06,080 SURVIVORS OF ARDS. 119 00:05:06,080 --> 00:05:10,920 WE CHALLENGE YOU AND HOPE THAT 120 00:05:10,920 --> 00:05:13,840 YOU WILL SEND HIGH RISK HIGH 121 00:05:13,840 --> 00:05:15,880 REWARD IDEAS ON HOW TO MOVE 122 00:05:15,880 --> 00:05:17,160 FORWARD SCIENCE IN THIS FIELD 123 00:05:17,160 --> 00:05:20,200 SO THAT ULTIMATELY WE CAN 124 00:05:20,200 --> 00:05:22,960 ACHIEVE A LONG-TERM OBJECTIVE 125 00:05:22,960 --> 00:05:28,400 OF IDENTIFYING ACTIONABLE 126 00:05:28,400 --> 00:05:29,800 TARGET INTERVENTION AND 127 00:05:29,800 --> 00:05:31,800 STRATEGIES THAT WILL REALLY 128 00:05:31,800 --> 00:05:36,960 HELP IMPROVE THE OPTIONS FOR 129 00:05:36,960 --> 00:05:38,320 PATIENTS. 130 00:05:38,320 --> 00:05:40,560 SO THOSE ARE YOUR REQUESTS 131 00:05:40,560 --> 00:05:42,040 FROM NHLBI TODAY. 132 00:05:42,040 --> 00:05:44,240 THOSE ARE ALSO OUR CHALLENGES. 133 00:05:44,240 --> 00:05:46,280 IT IS AN AMAZING PANEL. 134 00:05:46,280 --> 00:05:47,640 I HAVE TO APOLOGIZE AHEAD OF 135 00:05:47,640 --> 00:05:49,760 TIME BECAUSE I WILL HAVE TO BE 136 00:05:49,760 --> 00:05:53,920 IN AND OUT THROUGHOUT THE NEXT 137 00:05:53,920 --> 00:05:56,880 TWO DAYS BUT I WILL ATTEMPT TO 138 00:05:56,880 --> 00:05:58,160 ATTEND AS MANY SESSIONS AS I 139 00:05:58,160 --> 00:06:01,600 CAN AND HAVING SAID THAT, I 140 00:06:01,600 --> 00:06:10,000 WILL THANK YOU ALL AND RETURN 141 00:06:10,000 --> 00:06:12,680 THE MIC TO THE MODERATOR. 142 00:06:12,680 --> 00:06:13,840 >>THANK YOU VERY MUCH, BUS, 143 00:06:13,840 --> 00:06:24,400 SO I WOULD LIKE TO THANK THE 144 00:06:25,080 --> 00:06:27,360 NHLBI FOR THE WORKSHOP, IF YOU 145 00:06:27,360 --> 00:06:29,120 HAVE ANY QUESTIONS IN THE NEXT 146 00:06:29,120 --> 00:06:30,720 TWO DAYS, PLEASE REACH OUT TO 147 00:06:30,720 --> 00:06:31,000 THEM. 148 00:06:31,000 --> 00:06:35,280 I WOULD ALSO LIKE TO ALSO 149 00:06:35,280 --> 00:06:39,880 THANK MY COLLEAGUE, Dr. 150 00:06:39,880 --> 00:06:42,080 CHRISTIAN GOMEZ WHO HAS BEEN 151 00:06:42,080 --> 00:06:43,680 WORKING TAKING FOR THE LAST 152 00:06:43,680 --> 00:06:45,600 YEAR WHEN WE PLANNED TO HAVE 153 00:06:45,600 --> 00:06:46,600 THIS WORKSHOP. 154 00:06:46,600 --> 00:06:50,280 NOW I TURN THE MICROPHONE OVER 155 00:06:50,280 --> 00:06:52,320 TO Dr. CHRISTIAN. 156 00:06:52,320 --> 00:06:53,000 >>GOOD MORNING, EVERYONE, 157 00:06:53,000 --> 00:06:55,480 THANK YOU FOR THIS WORKSHOP. 158 00:06:55,480 --> 00:07:01,920 MY NAME IS CHRISTIAN GOMEZ -- 159 00:07:01,920 --> 00:07:02,360 [INDISCERNIBLE] 160 00:07:02,360 --> 00:07:12,880 THE FOCUS OF THIS IS THE. 161 00:07:14,840 --> 00:07:15,240 [INDISCERNIBLE] 162 00:07:15,240 --> 00:07:15,840 SO COMORBIDITIES IMPAIR 163 00:07:15,840 --> 00:07:17,920 QUALITY OF LIFE IN PHYSICAL 164 00:07:17,920 --> 00:07:18,800 AND MENTAL HEALTH. 165 00:07:18,800 --> 00:07:22,520 THE HIGH COST OF SURVIVING 166 00:07:22,520 --> 00:07:29,720 ARDS CAN BE VERY RELATED TO 167 00:07:29,720 --> 00:07:30,320 DEVELOPING PNEUMONIA OF 168 00:07:30,320 --> 00:07:32,480 SURVIVORS OF THIS CONDITION. 169 00:07:32,480 --> 00:07:39,120 IT IS MY DISTINCT PLEASURE TO 170 00:07:39,120 --> 00:07:43,240 INVITE Dr. KIRSTEN HARRELL 171 00:07:43,240 --> 00:07:48,440 WHO HAS BEEN WORKING WITH 172 00:07:48,440 --> 00:07:57,040 PATIENTS WITH HIGH RESULTS. 173 00:07:57,040 --> 00:08:03,320 ADDITIONALLY, MS. HARRELL IS A 174 00:08:03,320 --> 00:08:07,080 WRITER, SPEAKER AND WAS 175 00:08:07,080 --> 00:08:10,880 ACCEPTED TO -- 176 00:08:10,880 --> 00:08:15,240 [INDISCERNIBLE] 177 00:08:15,240 --> 00:08:15,800 WELCOME KIRSTEN. 178 00:08:15,800 --> 00:08:18,680 PLEASE TAKE IT AWAY. 179 00:08:18,680 --> 00:08:21,320 >>THANK YOU, Dr. GOMEZ. 180 00:08:21,320 --> 00:08:24,440 FIRST I WOULD LIKE TO EXPRESS 181 00:08:24,440 --> 00:08:26,200 MY GRATITUDE TO NIH AND TO ALL 182 00:08:26,200 --> 00:08:30,080 OF YOU FOR YOUR RESEARCH AND 183 00:08:30,080 --> 00:08:31,400 DEDICATION IN UNDERSTANDING 184 00:08:31,400 --> 00:08:33,720 ARDS AND HELPING SURVIVORS 185 00:08:33,720 --> 00:08:34,160 LIKE ME. 186 00:08:34,160 --> 00:08:36,120 I AM HONORED TO BE HERE TO 187 00:08:36,120 --> 00:08:39,080 SHARE MY STORY WITH ALL OF 188 00:08:39,080 --> 00:08:40,040 YOU. 189 00:08:40,040 --> 00:08:42,040 IT IS A LITTLE DIFFICULT FOR 190 00:08:42,040 --> 00:08:44,000 ME TO SPEAK ABOUT SO I AM 191 00:08:44,000 --> 00:08:48,000 GOING TO BE READING MY TALK 192 00:08:48,000 --> 00:08:52,280 BECAUSE SOME OF THE IMPACTS 193 00:08:52,280 --> 00:08:53,840 THAT I STILL EXPERIENCE MAKE 194 00:08:53,840 --> 00:08:55,400 IT A LITTLE DIFFICULT FOR ME 195 00:08:55,400 --> 00:08:58,320 TO KEEP TRACK AND KEEP ON 196 00:08:58,320 --> 00:08:59,680 TARGET HERE. 197 00:08:59,680 --> 00:09:05,080 SOME OF THE MAJOR HARDSHIPS 198 00:09:05,080 --> 00:09:08,120 THAT I EXPERIENCED WITHIN THE 199 00:09:08,120 --> 00:09:10,080 ICU INCLUDE FEELING COMPLETELY 200 00:09:10,080 --> 00:09:11,440 AND UTTERLY HELPLESS WHEN I 201 00:09:11,440 --> 00:09:13,280 WAS NOT ABLE TO COMMUNICATE. 202 00:09:13,280 --> 00:09:14,880 THERE WERE A FEW TIMES 203 00:09:14,880 --> 00:09:17,040 INITIALLY WHEN I WAS AWAKE 204 00:09:17,040 --> 00:09:20,160 THAT I COULD WRITE BUT THEN 205 00:09:20,160 --> 00:09:23,320 THAT ABILITY SHARPLY DECLINED 206 00:09:23,320 --> 00:09:25,800 THROUGHOUT MY TWO WEEKS ON A 207 00:09:25,800 --> 00:09:27,720 VENTILATOR AND AT OTHER TIMES 208 00:09:27,720 --> 00:09:31,160 WHEN I WAS AWAKE, AND I CAN 209 00:09:31,160 --> 00:09:34,160 REMEMBER PUTTING JUST AN 210 00:09:34,160 --> 00:09:35,880 ENORMOUS EFFORT INTO TRYING TO 211 00:09:35,880 --> 00:09:38,800 WRITE SOMETHING TO THE STAFF 212 00:09:38,800 --> 00:09:39,960 OR FAMILY AND THEN I WOULD 213 00:09:39,960 --> 00:09:42,040 SHOW IT TO THEM AND THEY 214 00:09:42,040 --> 00:09:43,840 COULDN'T READ IT AND I WOULD 215 00:09:43,840 --> 00:09:47,120 JUST BE SO FRUSTRATED AND 216 00:09:47,120 --> 00:09:49,120 THINKING I JUST SPENT EVERY 217 00:09:49,120 --> 00:09:50,600 LITTLE OUNCE OF ENERGY I HAD 218 00:09:50,600 --> 00:09:53,240 TO WRITE THAT AND WHY AREN'T 219 00:09:53,240 --> 00:09:55,400 THEY ABLE TO READ IT. 220 00:09:55,400 --> 00:09:56,480 OF COURSE I DIDN'T REALIZE 221 00:09:56,480 --> 00:09:59,640 THAT IT WAS BASICALLY CHICKE N 222 00:09:59,640 --> 00:10:02,840 SCRATCH AND THEY COULDN'T READ 223 00:10:02,840 --> 00:10:04,440 IT. 224 00:10:04,440 --> 00:10:09,680 I EXPERIENCED DELEAR YUM AND 225 00:10:09,680 --> 00:10:10,320 INDOZENS TERRIFYING 226 00:10:10,320 --> 00:10:10,800 HALLUCINATIONS. 227 00:10:10,800 --> 00:10:12,400 FOR EXAMPLE, I THOUGHT THAT I 228 00:10:12,400 --> 00:10:15,280 HAD BEEN KIDNAPPED AND HELD 229 00:10:15,280 --> 00:10:18,440 HOSTAGE FOR WEEKS IN A 230 00:10:18,440 --> 00:10:20,680 RESEARCH FACILITY WHERE THEY 231 00:10:20,680 --> 00:10:22,360 WERE EXPERIMENTING ON ME AND 232 00:10:22,360 --> 00:10:25,160 KEPT ME FROM MY FAMILY, THAT I 233 00:10:25,160 --> 00:10:26,040 WAS ALONE AND TRAPPED AND 234 00:10:26,040 --> 00:10:27,440 TRYING TO GET OUT. 235 00:10:27,440 --> 00:10:29,400 I HAD OTHER VIVID 236 00:10:29,400 --> 00:10:31,680 HALLUCINATIONS THAT CONTINUED 237 00:10:31,680 --> 00:10:33,040 UNTIL I WAS DISCHARGED. 238 00:10:33,040 --> 00:10:35,360 WHEN I FIRST GOT OFF THE 239 00:10:35,360 --> 00:10:37,200 VENTILATOR, I HAD TO LEARN HOW 240 00:10:37,200 --> 00:10:39,360 TO WALK AGAIN AND I CAN 241 00:10:39,360 --> 00:10:42,320 REMEMBER IN THE HOSPITAL THE 242 00:10:42,320 --> 00:10:46,640 FIRST FEW STEPS THAT I TOOK 243 00:10:46,640 --> 00:10:47,280 WERE SO DIFFICULT. 244 00:10:47,280 --> 00:10:49,360 I HAD TROUBLE TRYING TO GET MY 245 00:10:49,360 --> 00:10:52,760 BRAIN AND MY BODY TO WORK 246 00:10:52,760 --> 00:10:53,120 TOGETHER. 247 00:10:53,120 --> 00:10:55,600 THEY WOULD TELL ME TO LIFT A 248 00:10:55,600 --> 00:10:58,000 FOOT, I WOULD THINK THAT, IT 249 00:10:58,000 --> 00:11:00,080 WOULD TAKE QUITE A LONG TIME 250 00:11:00,080 --> 00:11:01,400 BEFORE MY BODY WOULD RESPOND 251 00:11:01,400 --> 00:11:03,120 AND I COULD LIFT THE FOOT AND 252 00:11:03,120 --> 00:11:05,200 THEN TRYING TO FIGURE OUT HOW 253 00:11:05,200 --> 00:11:07,600 TO LIFT ANOTHER FOOT, STAY 254 00:11:07,600 --> 00:11:09,160 BALANCED, HOLD THE WALKER AND 255 00:11:09,160 --> 00:11:11,840 BREATHE ALL AT THE SAME TIME 256 00:11:11,840 --> 00:11:13,880 SEEMED LIKE AN ABSOLUTELY 257 00:11:13,880 --> 00:11:15,640 IMPOSSIBLE TASK AT THAT POINT. 258 00:11:15,640 --> 00:11:19,240 I COULD ONLY DO A FEW STEPS AT 259 00:11:19,240 --> 00:11:23,200 A TIME BEFORE I WOULD FATIGUE 260 00:11:23,200 --> 00:11:30,200 AND HAVE TO SIT BACK DOWN. 261 00:11:30,200 --> 00:11:31,680 WHEN I FIRST GOT HOME, 262 00:11:31,680 --> 00:11:33,800 EVERYBODY WAS SO HAPPY AND 263 00:11:33,800 --> 00:11:37,240 GRATEFUL THAT I HAD SURVIVED. 264 00:11:37,240 --> 00:11:39,240 FOR ME THE LONG AND DIFFICULT 265 00:11:39,240 --> 00:11:40,720 ROAD TO RECOVERY WAS JUST 266 00:11:40,720 --> 00:11:41,080 BEGINNING. 267 00:11:41,080 --> 00:11:43,680 I WAS STILL VERY WEAK. 268 00:11:43,680 --> 00:11:47,280 I REMEMBER THAT IT TOOK ME A 269 00:11:47,280 --> 00:11:50,400 MONTH OF VERY HARD WORK WITH 270 00:11:50,400 --> 00:11:52,480 PHYSICAL THERAPY BEFORE I WAS 271 00:11:52,480 --> 00:11:53,480 EVEN RELEASED TO WALK BY 272 00:11:53,480 --> 00:11:56,280 MYSELF WITH A WALKER TO THE 273 00:11:56,280 --> 00:11:56,640 BATHROOM. 274 00:11:56,640 --> 00:11:59,200 BEFORE THAT, I ALWAYS HAD TO 275 00:11:59,200 --> 00:12:00,520 HAVE SOMEONE BEHIND ME BECAUSE 276 00:12:00,520 --> 00:12:03,240 I HAD A TENDENCY TO FALL 277 00:12:03,240 --> 00:12:03,920 BACKWARDS. 278 00:12:03,920 --> 00:12:07,560 I HAD DIFFICULTY SWALLOWING 279 00:12:07,560 --> 00:12:09,200 DUE TO VOCAL CORD DAMAGE AND I 280 00:12:09,200 --> 00:12:11,560 HAD TO EAT ONLY SOFT FOODS FOR 281 00:12:11,560 --> 00:12:12,880 QUITE A LONG TIME. 282 00:12:12,880 --> 00:12:14,240 ALL THE PILLS I HAD TO TAKE 283 00:12:14,240 --> 00:12:18,480 HAD TO BE CRUSHED AND MIXED 284 00:12:18,480 --> 00:12:19,240 WITH APPLE SAUCE. 285 00:12:19,240 --> 00:12:21,120 I HAD GREAT CARE FROM THE 286 00:12:21,120 --> 00:12:22,720 PHYSICAL THERAPY AND IT WAS 287 00:12:22,720 --> 00:12:24,320 REALLY HELPFUL TO HAVE THE 288 00:12:24,320 --> 00:12:29,280 GUIDANCE AND GOALS AND 289 00:12:29,280 --> 00:12:30,040 SPECIFIC TASKS. 290 00:12:30,040 --> 00:12:32,960 SO THAT FIRST YEAR WAS SPENT 291 00:12:32,960 --> 00:12:35,320 REGAINING MY ABILITY TO WALK, 292 00:12:35,320 --> 00:12:38,000 INCREASE MY STRENGTH, MY 293 00:12:38,000 --> 00:12:40,320 BALANCE, ENDURANCE. 294 00:12:40,320 --> 00:12:42,720 UNFORTUNATELY THE SAME TYPE OF 295 00:12:42,720 --> 00:12:43,640 CARE AND STRUCTURE WASN'T 296 00:12:43,640 --> 00:12:46,760 THERE FOR THE COGNITIVE AND 297 00:12:46,760 --> 00:12:48,680 PSYCHOLOGICAL RECOVERY AND SO 298 00:12:48,680 --> 00:12:50,880 THAT PART FOR ME HAS BEEN THE 299 00:12:50,880 --> 00:12:53,200 HARDEST AND MOST CHALLENGING 300 00:12:53,200 --> 00:12:58,800 ASPECT OF RECOVERY FROM THE 301 00:12:58,800 --> 00:12:59,800 ARDS FROM THE ICU. 302 00:12:59,800 --> 00:13:02,320 WHEN I WAS IN THE ICU, MY 303 00:13:02,320 --> 00:13:05,360 FAMILY WAS TOLD I MAY HAVE 304 00:13:05,360 --> 00:13:06,640 SOME COGNITIVE IMPAIRMENTS BUT 305 00:13:06,640 --> 00:13:07,800 WEREN'T GIVEN ANY OTHER 306 00:13:07,800 --> 00:13:09,120 INFORMATION OR REFERRALS OR 307 00:13:09,120 --> 00:13:11,440 ASSISTANCE FOR HOW TO HELP ME. 308 00:13:11,440 --> 00:13:14,560 I HAD A LOT OF CONFUSION AT 309 00:13:14,560 --> 00:13:18,520 FIRST AND VERY SIGNIFICANT 310 00:13:18,520 --> 00:13:21,800 COGNITIVE DIFFICULTIES EARLY 311 00:13:21,800 --> 00:13:23,160 ON. 312 00:13:23,160 --> 00:13:24,720 THOSE JUST SLOWLY IMPROVED 313 00:13:24,720 --> 00:13:27,280 OVER TIME. 314 00:13:27,280 --> 00:13:31,160 I SOUGHT SOME HELP FROM MY PCP 315 00:13:31,160 --> 00:13:32,240 AND NEUROLOGIST. 316 00:13:32,240 --> 00:13:34,480 UNFORTUNATELY THEY DID NOT 317 00:13:34,480 --> 00:13:36,320 KNOW ANYTHING ABOUT IT AND DID 318 00:13:36,320 --> 00:13:37,920 NOT OFFER ANY HELP. 319 00:13:37,920 --> 00:13:41,360 I DECIDED TO TRY THINGS ON MY 320 00:13:41,360 --> 00:13:42,760 OWN LIKE PUZZLES AND GAMES. 321 00:13:42,760 --> 00:13:44,720 I HAD GREAT DIFFICULTY READING 322 00:13:44,720 --> 00:13:46,640 AND READING HAS ALWAYS BEEN A 323 00:13:46,640 --> 00:13:48,040 HUGE LOVE OF MINE SO I WAS 324 00:13:48,040 --> 00:13:50,000 DETERMINED TO TRY TO INCREASE 325 00:13:50,000 --> 00:13:52,200 MY FOCUS AND ATTENTION SO I 326 00:13:52,200 --> 00:13:54,280 COULD ENJOY READING AGAIN. 327 00:13:54,280 --> 00:13:56,560 IT DID IMPROVE OVER TIME, 328 00:13:56,560 --> 00:13:57,840 HOWEVER I STILL HAVE TROUBLE 329 00:13:57,840 --> 00:14:00,240 AT TIMES AND CANNOT FOCUS 330 00:14:00,240 --> 00:14:02,960 ENOUGH TO READ AND IT IS VERY 331 00:14:02,960 --> 00:14:06,280 FRUSTRATING AND AT TIMES 332 00:14:06,280 --> 00:14:08,320 DEPRESSING. 333 00:14:08,320 --> 00:14:15,320 I CONTINUE TO HAVE EXPERIENCED 334 00:14:15,320 --> 00:14:16,600 SOME MILD DEFICIT DISFUNCTIONS 335 00:14:16,600 --> 00:14:18,880 THAT INTERFERE WITH MY DAILY 336 00:14:18,880 --> 00:14:19,160 LIFE. 337 00:14:19,160 --> 00:14:21,600 IN SOME OF THE DISFUNCTIONS I 338 00:14:21,600 --> 00:14:22,960 CAN SUSTAIN FAIRLY WELL BUT 339 00:14:22,960 --> 00:14:23,840 NOT FOR LONG. 340 00:14:23,840 --> 00:14:26,840 IF I AM FATIGUED I STRUGGLE 341 00:14:26,840 --> 00:14:27,400 WITH COGNITIVE TASKS. 342 00:14:27,400 --> 00:14:29,280 I HAVE TROUBLE WITH ORGANIZING 343 00:14:29,280 --> 00:14:31,240 AND PLANNING AND COMPLETING 344 00:14:31,240 --> 00:14:33,080 TASKS WITH MULTIPLE STEPS. 345 00:14:33,080 --> 00:14:34,240 SWITCHING GEARS IS CHALLENGING 346 00:14:34,240 --> 00:14:36,480 AND I FIND THAT I NEED A LOT 347 00:14:36,480 --> 00:14:40,200 OF STRUCTURE IN ROUTINES THAT 348 00:14:40,200 --> 00:14:46,880 I DIDN'T NEED BEFORE BECAUSE 349 00:14:46,880 --> 00:14:49,160 CHANGE CAN REALLY DERAIL ME. 350 00:14:49,160 --> 00:14:51,040 AS A PSYCHOLOGIST, IT TOOK ME 351 00:14:51,040 --> 00:14:53,920 SOME TIME TO REALIZE I WAS 352 00:14:53,920 --> 00:14:55,720 EXPERIENCING PTSD FROM THE 353 00:14:55,720 --> 00:14:56,520 ICU. 354 00:14:56,520 --> 00:15:05,440 I HAD TO LEARN ABOUT PIS. 355 00:15:05,440 --> 00:15:08,880 I TRIED TO READ ABOUT THAT BUT 356 00:15:08,880 --> 00:15:10,800 THE THERAPISTS LACK OF 357 00:15:10,800 --> 00:15:12,560 UNDERSTANDING ABOUT IT MADE 358 00:15:12,560 --> 00:15:14,680 THE TREATMENT INEFFECTIVE. 359 00:15:14,680 --> 00:15:17,120 AS AN ARDS SURVIVOR WITH 360 00:15:17,120 --> 00:15:17,720 IMMUNE DEFICIENCY, THE 361 00:15:17,720 --> 00:15:20,640 PANDEMIC FOR ME WAS MY WORST 362 00:15:20,640 --> 00:15:26,000 NIGHTMARE COME TRUE AND 363 00:15:26,000 --> 00:15:29,000 GREATLY SASS EXACERBATED MY 364 00:15:29,000 --> 00:15:31,400 PTSD AND SENT ME INTO CRISIS. 365 00:15:31,400 --> 00:15:33,560 IT WAS LIKE LIVING IN A 366 00:15:33,560 --> 00:15:35,640 CONSTANT STATE OF TRIGGERING 367 00:15:35,640 --> 00:15:36,640 AND AT TIMES I WONDERED IF I 368 00:15:36,640 --> 00:15:44,680 WAS STILL IN THE ICU 369 00:15:44,680 --> 00:15:45,960 EXPERIENCINGDELERIUM BECAUSE 370 00:15:45,960 --> 00:15:49,480 IT SEEMED TO UNBELIEVABLE TO 371 00:15:49,480 --> 00:15:51,000 ME. 372 00:15:51,000 --> 00:15:52,520 THE DELERIUM AND 373 00:15:52,520 --> 00:16:00,720 HALLUCINATIONS STILL HAUNT ME. 374 00:16:00,720 --> 00:16:03,440 AND WITH LIVED TRAUMATIC 375 00:16:03,440 --> 00:16:05,160 EXPERIENCES, EVEN THOUGH I 376 00:16:05,160 --> 00:16:08,520 KNOW THEY ARE NOT REAL, MY 377 00:16:08,520 --> 00:16:09,800 MIND STILL EXPERIENCES THOSE 378 00:16:09,800 --> 00:16:11,320 EXPERIENCES AS IF I LIVED 379 00:16:11,320 --> 00:16:14,000 THROUGH THEM. 380 00:16:14,000 --> 00:16:20,800 I SUFFER SEVERE PTSD, ANXIETY, 381 00:16:20,800 --> 00:16:23,080 EMOTIONAL LABILITY AND 382 00:16:23,080 --> 00:16:23,480 DEPRESSION. 383 00:16:23,480 --> 00:16:31,520 MY QUALITY OF LIFE IS REDUCED. 384 00:16:31,520 --> 00:16:32,920 I SUFFER DESPAIR, FLASHBACKS, 385 00:16:32,920 --> 00:16:35,040 IT TAKES TIME TO RECOVER AND 386 00:16:35,040 --> 00:16:36,080 IS PHYSICALLY EXHAUSTING. 387 00:16:36,080 --> 00:16:37,080 MEDICAL APPOINTMENTS AND 388 00:16:37,080 --> 00:16:38,560 PROCEDURES ARE DIFFICULT FOR 389 00:16:38,560 --> 00:16:40,840 ME NOW AND CAUSE A LOT OF 390 00:16:40,840 --> 00:16:41,200 ANXIETY. 391 00:16:41,200 --> 00:16:43,040 GOING TO THE EMERGENCY 392 00:16:43,040 --> 00:16:44,480 DEPARTMENT CAN BE VERY 393 00:16:44,480 --> 00:16:46,320 TRIGGERING AND AT TIMES TRAWL 394 00:16:46,320 --> 00:16:50,720 MATIZING BECAUSE OF THE LACK 395 00:16:50,720 --> 00:16:51,960 OF TRAUMA-INFORMED CARE. 396 00:16:51,960 --> 00:16:53,920 IT WASN'T TILL FOUR YEARS 397 00:16:53,920 --> 00:16:56,200 AFTER THE ICU THAT I FINALLY 398 00:16:56,200 --> 00:16:59,800 FOUND A SUPPORT GROUP AT THE 399 00:16:59,800 --> 00:17:02,320 VENDORRABILITY CENTER AND THE 400 00:17:02,320 --> 00:17:08,360 SUPPORT WITH THOSE WITH PIS I 401 00:17:08,360 --> 00:17:08,920 HAVE FOUND HELPFUL. 402 00:17:08,920 --> 00:17:11,920 I HAVE A THERAPIST WHO IS 403 00:17:11,920 --> 00:17:13,160 TRAUMA-INFORMED AND WILLING TO 404 00:17:13,160 --> 00:17:14,920 LEARN ABOUT THIS AND I AM 405 00:17:14,920 --> 00:17:16,640 MAKING PROGRESS AND JUST NOW 406 00:17:16,640 --> 00:17:20,720 STARTING TO FOCUS ON CREATING 407 00:17:20,720 --> 00:17:24,080 AWARENESS ABOUT ALD S&P IS AND 408 00:17:24,080 --> 00:17:25,480 HELP SOME OTHER SURVIVORS. 409 00:17:25,480 --> 00:17:27,240 SOME OF THE THINGS THAT CAN 410 00:17:27,240 --> 00:17:30,640 HELP ARE HAVING 411 00:17:30,640 --> 00:17:32,200 TRAUMA-INFORMED PROVIDERS IN 412 00:17:32,200 --> 00:17:32,920 THE ICU. 413 00:17:32,920 --> 00:17:35,880 THAT PERSON COULD HELP WITH 414 00:17:35,880 --> 00:17:38,440 MAJOR EVENTS, PROCEDURES, 415 00:17:38,440 --> 00:17:40,840 TRANSITIONS, HELP IDENTIFY 416 00:17:40,840 --> 00:17:43,160 DEALMOST ERIUM AND REDUCE THE 417 00:17:43,160 --> 00:17:43,640 TERROR. 418 00:17:43,640 --> 00:17:44,600 PROVIDE SOME CONTINUITY OF 419 00:17:44,600 --> 00:17:47,200 CARE IN THE STEPDOWN UNITS 420 00:17:47,200 --> 00:17:49,160 BECAUSE IT CAN BE REALLY SCARY 421 00:17:49,160 --> 00:17:52,040 TO GO FROM THE INTENSE AND 422 00:17:52,040 --> 00:17:55,880 CONSTANT CARE OF THE ICU TO A 423 00:17:55,880 --> 00:17:57,960 REGULAR FLOOR WITH LESS CARE, 424 00:17:57,960 --> 00:18:00,840 LESS PEOPLE, LESS ATTENTION. 425 00:18:00,840 --> 00:18:01,520 I THINK ACCEPTABLE 426 00:18:01,520 --> 00:18:02,320 COMMUNICATION TOOLS ARE 427 00:18:02,320 --> 00:18:03,920 ESSENTIAL TO REDUCE SOME OF 428 00:18:03,920 --> 00:18:05,360 THE HELPLESSNESS AND ANXIETY. 429 00:18:05,360 --> 00:18:08,760 THAT COULD ALSO HELP WITH THE 430 00:18:08,760 --> 00:18:10,280 DELERIUM BECAUSE I WAS 431 00:18:10,280 --> 00:18:11,800 TERRIFIED AND I COULDN'T TELL 432 00:18:11,800 --> 00:18:13,360 ANYONE WHY. 433 00:18:13,360 --> 00:18:14,960 AND FINALLY I THINK BETTER 434 00:18:14,960 --> 00:18:18,400 CONTINUITY OF CARE POST-ICU 435 00:18:18,400 --> 00:18:20,360 AND THAT INCLUDES EDUCATION 436 00:18:20,360 --> 00:18:21,640 FOR FAMILY ABOUT WHAT TO 437 00:18:21,640 --> 00:18:23,680 EXPECT AND HOW TO HELP THE 438 00:18:23,680 --> 00:18:27,720 SURVIVOR AS WELL AS THEY MIGHT 439 00:18:27,720 --> 00:18:29,680 EXPERIENCE THEIR OWN PTSD. 440 00:18:29,680 --> 00:18:31,880 REFERRAL TO PROVIDERS WHO ARE 441 00:18:31,880 --> 00:18:34,080 FAMILIAR WITH ARDS AND PIS 442 00:18:34,080 --> 00:18:37,560 WOULD BE VERY HELPFUL AND IF 443 00:18:37,560 --> 00:18:41,120 THERE COULD BE SOME STRUCTURE 444 00:18:41,120 --> 00:18:43,040 AND ASSISTANCE IN PLACE TO 445 00:18:43,040 --> 00:18:45,960 HELP WITH COGNITIVE AND 446 00:18:45,960 --> 00:18:46,960 PSYCHOLOGICAL RECOVERY EARLY 447 00:18:46,960 --> 00:18:49,000 ON, I AM CONVINCED I WOULDN'T 448 00:18:49,000 --> 00:18:50,280 HAVE SUFFERED AS GREATLY AND 449 00:18:50,280 --> 00:18:51,920 WOULD HAVE A BETTER QUALITY OF 450 00:18:51,920 --> 00:18:53,080 LIFE NOW IF I HAD RECEIVED 451 00:18:53,080 --> 00:18:56,560 THAT HELP EARLY ON. 452 00:18:56,560 --> 00:18:58,600 I KNOW I WOULD NOT HAVE 453 00:18:58,600 --> 00:19:01,600 SURVIVED ARDS WITHOUT THE ICU 454 00:19:01,600 --> 00:19:01,880 STAFF. 455 00:19:01,880 --> 00:19:03,720 MORE IMPORTANTLY, I WOULD NOT 456 00:19:03,720 --> 00:19:04,800 HAVE SURVIVED THE FOLLOWING 457 00:19:04,800 --> 00:19:06,960 FIVE YEARS WITHOUT THE AMAZING 458 00:19:06,960 --> 00:19:09,920 LOVE AND SUPPORT FROM MY 459 00:19:09,920 --> 00:19:13,120 FAMILY, FRIENDS, THE 460 00:19:13,120 --> 00:19:15,160 VANDERBILT PIS GROUP AND MY 461 00:19:15,160 --> 00:19:17,880 THERAPIST AS I FIGHT TO 462 00:19:17,880 --> 00:19:18,560 RECOVER FROM PIS. 463 00:19:18,560 --> 00:19:20,800 FINALLY I WANT TO THANK ALL OF 464 00:19:20,800 --> 00:19:22,680 YOU AGAIN FOR ALLOWING ME TO 465 00:19:22,680 --> 00:19:24,200 SHARE MY STORY WITH AND YOU 466 00:19:24,200 --> 00:19:26,480 FOR WORKING HARD TO DEVELOP A 467 00:19:26,480 --> 00:19:28,680 BETTER UNDERSTANDING AND 468 00:19:28,680 --> 00:19:29,440 TREATMENT FOR ARDS. 469 00:19:29,440 --> 00:19:37,000 THANK YOU SO MUCH. 470 00:19:37,000 --> 00:19:45,360 >>THANK YOU FOR YOUR 471 00:19:45,360 --> 00:19:45,920 INSPIRING TESTIMONY. 472 00:19:45,920 --> 00:19:48,320 IT IS SAID THE DARKEST HOUR OF 473 00:19:48,320 --> 00:19:53,160 THE NIGHT COMES JUST BEFORE 474 00:19:53,160 --> 00:19:54,800 THE DAWN. 475 00:19:54,800 --> 00:19:58,280 WITHOUT FURTHER ADIEU, LET ME 476 00:19:58,280 --> 00:20:08,840 INTRODUCE OUR COCHAIRS NOW, 477 00:20:12,000 --> 00:20:17,360 Dr. TERRI HOUGH AND Dr. 478 00:20:17,360 --> 00:20:18,400 GIRARD. 479 00:20:18,400 --> 00:20:21,520 Dr. HOUGH -- 480 00:20:21,520 --> 00:20:24,600 [INDISCERNIBLE] 481 00:20:24,600 --> 00:20:27,040 USING CLINICAL TRIALS AT 482 00:20:27,040 --> 00:20:28,240 CONVENTIONAL METHODS. 483 00:20:28,240 --> 00:20:32,880 Dr. GIRARD IS ASSISTANT 484 00:20:32,880 --> 00:20:34,160 PROFESSOR AT THE UNIVERSITY 485 00:20:34,160 --> 00:20:35,320 SCHOOL OF MEDICINE AND 486 00:20:35,320 --> 00:20:37,760 DIRECTOR OF THE UNIVERSITY'S 487 00:20:37,760 --> 00:20:38,560 CLINICAL RESEARCH, 488 00:20:38,560 --> 00:20:40,520 INVESTIGATOR OF SYSTEM 489 00:20:40,520 --> 00:20:47,480 MODELING OF ACUTE ILLNESS. 490 00:20:47,480 --> 00:20:52,920 HIS RESEARCH IS TO APPROACH 491 00:20:52,920 --> 00:20:56,080 LONG STANDING ILLNESS WITH 492 00:20:56,080 --> 00:20:56,960 SPECIFIC -- 493 00:20:56,960 --> 00:20:57,440 [INDISCERNIBLE] 494 00:20:57,440 --> 00:20:58,600 BEFORE I DELIVER THE MIC TO 495 00:20:58,600 --> 00:21:01,840 BOTH OF YOU, LET ME THANK YOU 496 00:21:01,840 --> 00:21:05,040 FROM NHLBI FOR YOUR LEADERSHIP 497 00:21:05,040 --> 00:21:06,120 AND COMMUNICATION FOR THIS 498 00:21:06,120 --> 00:21:06,480 WORKSHOP. 499 00:21:06,480 --> 00:21:11,040 IT HAS BEEN A PLEASURE WORKING 500 00:21:11,040 --> 00:21:13,240 WITH YOU. 501 00:21:13,240 --> 00:21:15,080 Dr. HOUGH, THE FLOOR IS 502 00:21:15,080 --> 00:21:15,400 YOURS. 503 00:21:15,400 --> 00:21:16,160 >>THANK YOU SO MUCH AND 504 00:21:16,160 --> 00:21:18,920 THANKS TO THE WHOLE TEAM OF 505 00:21:18,920 --> 00:21:20,200 NHLBI FOR FOCUSING ON THIS 506 00:21:20,200 --> 00:21:22,280 WORK AND I LOOK FORWARD TO THE 507 00:21:22,280 --> 00:21:23,880 NEXT TWO DAYS TOGETHER BUT 508 00:21:23,880 --> 00:21:27,760 FIRST OF ALL THANK YOU TO 509 00:21:27,760 --> 00:21:30,400 Dr. HARRELL FOR SHARING YOUR 510 00:21:30,400 --> 00:21:32,160 STORY AND PUTTING A FACE AND 511 00:21:32,160 --> 00:21:33,880 FOCUS ON THE WORK WE HAVE ALL 512 00:21:33,880 --> 00:21:41,880 BEEN FOCUSSED ON FOR OUR 513 00:21:41,880 --> 00:21:43,400 CAREERS AND HELPING US 514 00:21:43,400 --> 00:21:44,440 UNDERSTAND THIS WORK IS 515 00:21:44,440 --> 00:21:46,600 CRUCIAL AND WE STILL HAVE 516 00:21:46,600 --> 00:21:47,320 SIGNIFICANT GROUND TO COVER IN 517 00:21:47,320 --> 00:21:49,920 ORDER TO BE ABLE TO MOVE THE 518 00:21:49,920 --> 00:21:51,440 NEEDLE AND OUTCOMES THE WAY WE 519 00:21:51,440 --> 00:21:51,920 HOPE TO. 520 00:21:51,920 --> 00:21:56,160 WE HAVE A COUPLE OF SLIDES TO 521 00:21:56,160 --> 00:21:57,640 START AND I DON'T KNOW WHO IS 522 00:21:57,640 --> 00:22:04,840 GOING TO PUT THOSE ON? 523 00:22:04,840 --> 00:22:06,040 AH, OKAY, EXCELLENT. 524 00:22:06,040 --> 00:22:07,960 SO Dr. GIRARD AND I WILL 525 00:22:07,960 --> 00:22:09,960 JUST TAKE A FEW MOMENTS TO SET 526 00:22:09,960 --> 00:22:14,800 THE STAGE FOR THE NEXT FEW 527 00:22:14,800 --> 00:22:16,240 DAYS AND I THINK WE WILL COVER 528 00:22:16,240 --> 00:22:21,200 A LOT OF WHAT WE HAVE ALREADY 529 00:22:21,200 --> 00:22:29,760 HEARD FROM Dr. MATUTE-BELLO 530 00:22:29,760 --> 00:22:31,920 AND Dr. GOMEZ AND Dr. 531 00:22:31,920 --> 00:22:32,520 HARRELL. 532 00:22:32,520 --> 00:22:35,120 NEXT SLIDE, PLEASE. 533 00:22:35,120 --> 00:22:45,720 SO WE KNOW ACUTE RESPIRATORY 534 00:22:47,800 --> 00:22:49,480 DEPRESS SIT SYNDROME IS 535 00:22:49,480 --> 00:22:49,880 COMMON. 536 00:22:49,880 --> 00:22:51,840 I FIRST LEARNED ABOUT THIS 537 00:22:51,840 --> 00:22:54,640 THROUGH WORK AT THE UNIVERSITY 538 00:22:54,640 --> 00:22:58,280 OF WASHINGTON AND IT SHOWED 539 00:22:58,280 --> 00:23:01,400 RATHER THAN BEING THE WEIRD 540 00:23:01,400 --> 00:23:02,640 OUTCOME THAT WAS CONSIDERED AT 541 00:23:02,640 --> 00:23:06,280 THE TIME, IT WAS FAIRLY 542 00:23:06,280 --> 00:23:06,600 COMMON. 543 00:23:06,600 --> 00:23:09,760 WHAT WAS DERIVED FROM THIS 544 00:23:09,760 --> 00:23:12,160 WORK WAS ALMOST 90 CASES OUT 545 00:23:12,160 --> 00:23:15,440 OF 100 AND AN ESTIMATED 546 00:23:15,440 --> 00:23:18,400 200,000 A CASES ACROSS THE 547 00:23:18,400 --> 00:23:19,120 UNITED STATES. 548 00:23:19,120 --> 00:23:20,160 NEXT SLIDE, PLEASE. 549 00:23:20,160 --> 00:23:22,760 OBVIOUSLY IN THE AGE OF 550 00:23:22,760 --> 00:23:24,480 COVID-19, ARDS IS CLEARLY NOT 551 00:23:24,480 --> 00:23:27,040 A RARE DISEASE AND THE 552 00:23:27,040 --> 00:23:28,840 DRAMATIC INCREASE IN NUMBERS 553 00:23:28,840 --> 00:23:31,320 AND RECOGNITION OF ARDS HAS 554 00:23:31,320 --> 00:23:33,080 REALLY COME TO THE FRONT OVER 555 00:23:33,080 --> 00:23:34,720 THE LAST FEW YEARS. 556 00:23:34,720 --> 00:23:36,920 I THINK WE CAN SAFELY ASSUME 557 00:23:36,920 --> 00:23:39,920 THAT THE VAST MAJORITY OF 558 00:23:39,920 --> 00:23:41,400 HOSPITALIZATIONS FOR COVID-19 559 00:23:41,400 --> 00:23:42,720 INCLUDED ARDS OR SOMETHING 560 00:23:42,720 --> 00:23:46,680 VERY SIMILAR AND THE NUMBERS 561 00:23:46,680 --> 00:23:51,120 ARE TRULY STAGGERING. 562 00:23:51,120 --> 00:23:55,960 JUST IN THE THIRD YEAR OF THE 563 00:23:55,960 --> 00:23:56,960 PANDEMIC, ONLY 3.5 MILLION 564 00:23:56,960 --> 00:23:59,160 CASES ALONE. 565 00:23:59,160 --> 00:24:00,200 NEXT SLIDE, PLEASE. 566 00:24:00,200 --> 00:24:01,360 AND FORTUNATELY WE'RE ALSO 567 00:24:01,360 --> 00:24:04,080 SEEING A TREND OF INCREASING 568 00:24:04,080 --> 00:24:06,000 SURVIVAL AFTER ARDS 569 00:24:06,000 --> 00:24:06,720 HOSPITALIZATION. 570 00:24:06,720 --> 00:24:08,080 THERE IS SOME WORK LOOKING 571 00:24:08,080 --> 00:24:09,720 KIND OF OVER THE FIRST 30 572 00:24:09,720 --> 00:24:13,760 YEARS OF ARDS AND SHOWING A 573 00:24:13,760 --> 00:24:16,360 PRETTY DRAMATIC DECREASE IN 574 00:24:16,360 --> 00:24:17,160 HOSPITAL MORTALITY FROM 575 00:24:17,160 --> 00:24:18,360 50 PERCENT TO LESS THAN 576 00:24:18,360 --> 00:24:20,360 30 PERCENT OVER THAT PERIOD OF 577 00:24:20,360 --> 00:24:20,640 TIME. 578 00:24:20,640 --> 00:24:21,480 NEXT SLIDE. 579 00:24:21,480 --> 00:24:22,880 SO EVEN IF IT IS A LITTLE 580 00:24:22,880 --> 00:24:25,160 EARLY IN YOUR TIME ZONE AS IT 581 00:24:25,160 --> 00:24:29,400 IS FOR MINE TO DO MATH, IT IS 582 00:24:29,400 --> 00:24:31,320 EASY TO CALCULATE THIS. 583 00:24:31,320 --> 00:24:32,840 EVERY YEAR THERE ARE HUNDREDS 584 00:24:32,840 --> 00:24:36,360 OF THOUSANDS OF ARDS SURVIVORS 585 00:24:36,360 --> 00:24:38,320 JUST IN THIS COUNTRY -- 586 00:24:38,320 --> 00:24:39,720 [INDISCERNIBLE] 587 00:24:39,720 --> 00:24:40,840 NEXT SLIDE, PLEASE. 588 00:24:40,840 --> 00:24:43,600 SO THE ISSUES THAT Dr. 589 00:24:43,600 --> 00:24:46,120 HARRELL DESCRIBED IN HER 590 00:24:46,120 --> 00:24:48,640 RECOVERY FROM ARDS ARE JUST AS 591 00:24:48,640 --> 00:24:49,560 STARTLING AND STAGGERING NOW 592 00:24:49,560 --> 00:24:51,320 AS THEY HAVE BEEN FOR YEARS 593 00:24:51,320 --> 00:24:53,000 BUT THEY ARE CERTAINLY NOT 594 00:24:53,000 --> 00:24:53,280 NEW. 595 00:24:53,280 --> 00:24:54,880 THIS IS NOT NEW INFORMATION. 596 00:24:54,880 --> 00:24:59,080 WE HAVE STUDIED BACK TO THE 597 00:24:59,080 --> 00:25:01,000 1990S DESCRIBING FUNCTIONAL 598 00:25:01,000 --> 00:25:03,520 IMPAIRMENT, THE COGNITIVE 599 00:25:03,520 --> 00:25:05,440 IMPAIRMENT THAT OUR PATIENTS 600 00:25:05,440 --> 00:25:06,800 STRUGGLE WITH AFTER ARDS. 601 00:25:06,800 --> 00:25:10,440 IT HAS NOW BEEN 20 YEARS SINCE 602 00:25:10,440 --> 00:25:11,800 THE LANDMARK STUDY FOLLOWING 603 00:25:11,800 --> 00:25:13,680 ARDS PATIENTS FOR A YEAR AND 604 00:25:13,680 --> 00:25:16,200 THEN FIVE YEARS AFTER THEIR 605 00:25:16,200 --> 00:25:20,120 CRITICAL ILLNESS AND AGAIN 606 00:25:20,120 --> 00:25:28,120 THIS IS DEMONSTRATING THE 607 00:25:28,120 --> 00:25:31,800 MARKED IMPAIRMENT AND HEALTH 608 00:25:31,800 --> 00:25:33,400 STATUS OF PATIENTS. 609 00:25:33,400 --> 00:25:34,200 NEXT SLIDE, PLEASE. 610 00:25:34,200 --> 00:25:35,440 AND TRYING TO FIGURE THIS OUT 611 00:25:35,440 --> 00:25:38,080 WE HAVE KIND OF LOOKED ACROSS 612 00:25:38,080 --> 00:25:40,360 THE TRAJECTORY AND ARC OF 613 00:25:40,360 --> 00:25:42,280 RECOVERY OF OUR PATIENTS AFTER 614 00:25:42,280 --> 00:25:44,880 ARDS AND A LOT OF OUR WORK IS 615 00:25:44,880 --> 00:25:47,240 FOCUSED ON THE EARLY CASES. 616 00:25:47,240 --> 00:25:49,640 AGAIN, IT HAS NOW BEEN 20 617 00:25:49,640 --> 00:25:55,120 YEARS SINCE WE FIRST READ 618 00:25:55,120 --> 00:25:57,840 ABOUT THE PARESIS IN A 619 00:25:57,840 --> 00:26:00,000 LANDMARK STUDY DONE BY OUR 620 00:26:00,000 --> 00:26:04,600 COLLEAGUES IN FRANCE AND 621 00:26:04,600 --> 00:26:08,360 SIMILARLY, THE DELIRIUM IN 622 00:26:08,360 --> 00:26:09,080 MECHANICALLY VENTILATED 623 00:26:09,080 --> 00:26:10,240 PATIENTS AND THEIR RECOVERY. 624 00:26:10,240 --> 00:26:11,000 SO PERHAPS TRYING TO 625 00:26:11,000 --> 00:26:14,000 UNDERSTAND SOME OF THE 626 00:26:14,000 --> 00:26:18,080 PRECOURSE SORES OF COGNITIVE 627 00:26:18,080 --> 00:26:20,240 ABILITY WE SEE AFTER THE 628 00:26:20,240 --> 00:26:21,320 ILLNESS, NEXT SLIDE, PLEASE, 629 00:26:21,320 --> 00:26:23,040 AND MANY OF US ON THIS CALL 630 00:26:23,040 --> 00:26:24,560 TODAY SPENT A LOT OF TIME 631 00:26:24,560 --> 00:26:26,880 TRYING TO IDENTIFY THE RISK 632 00:26:26,880 --> 00:26:28,360 FACTORS ASSOCIATED WITH THESE. 633 00:26:28,360 --> 00:26:30,760 AND THERE ARE MANY PAPERS OUT 634 00:26:30,760 --> 00:26:34,640 THERE COMPILING ALL THE 635 00:26:34,640 --> 00:26:36,440 DIFFERENT KINDS OF FEATURES 636 00:26:36,440 --> 00:26:41,280 ASSOCIATED WITH THE ILLNESS 637 00:26:41,280 --> 00:26:44,360 ITSELF AND THEN TRYING TO 638 00:26:44,360 --> 00:26:46,840 IDENTIFY ASPECTS OF CARE AND 639 00:26:46,840 --> 00:26:48,840 RISKS OF ACUTE MUSCLE AND 640 00:26:48,840 --> 00:26:50,760 BRAIN DYSFUNCTION AS WELL. 641 00:26:50,760 --> 00:26:51,360 NEXT SLIDE. 642 00:26:51,360 --> 00:26:54,720 BUT DESPITE THE NOW DECADES OF 643 00:26:54,720 --> 00:26:56,840 WORK WE HAVE BEEN DOING, THE 644 00:26:56,840 --> 00:26:58,040 MANY ATTEMPTS AT USING 645 00:26:58,040 --> 00:27:00,320 INTERVENTION TO TRY TO IMPROVE 646 00:27:00,320 --> 00:27:04,280 THESE OUTCOMES HAVE REALLY NOT 647 00:27:04,280 --> 00:27:06,360 RESULTED IN THE CHANGE WE HAD 648 00:27:06,360 --> 00:27:07,720 HOPED AND MY GOODNESS THERE 649 00:27:07,720 --> 00:27:12,600 HAVE BEEN A LOT OF STUDIES AND 650 00:27:12,600 --> 00:27:14,720 CLINICAL IDEAS RANGING FROM 651 00:27:14,720 --> 00:27:16,920 REHABILITATION MANUALS AND 652 00:27:16,920 --> 00:27:18,440 EDUCATION, EXERCISE PROGRAMS, 653 00:27:18,440 --> 00:27:20,040 COGNITIVE THERAPY, PHYSICAL 654 00:27:20,040 --> 00:27:20,840 THERAPY, NUTRITION, MAKING 655 00:27:20,840 --> 00:27:22,760 SURE PEOPLE HAVE INFORMATION 656 00:27:22,760 --> 00:27:25,640 AND THEN TREATMENT TRYING TO 657 00:27:25,640 --> 00:27:26,680 HELP THE PSYCHOLOGICAL 658 00:27:26,680 --> 00:27:30,000 IMPAIRMENTS AS WELL, THE 659 00:27:30,000 --> 00:27:31,360 COPING SKILLS, MINDFULNESS, 660 00:27:31,360 --> 00:27:33,800 DIARIES AND MANY CLINICAL 661 00:27:33,800 --> 00:27:35,440 APPROACHES AND FOLLOW UP 662 00:27:35,440 --> 00:27:35,800 PROGRAMS. 663 00:27:35,800 --> 00:27:36,200 NEXT SLIDE. 664 00:27:36,200 --> 00:27:38,160 BUT I THINK LARGELY 665 00:27:38,160 --> 00:27:39,160 UNFORTUNATELY DESPITE THESE 666 00:27:39,160 --> 00:27:41,360 VERY GOOD IDEAS AND A LOT OF 667 00:27:41,360 --> 00:27:44,840 WORK, WE REALLY STILL LACK 668 00:27:44,840 --> 00:27:45,920 EVIDENCE-BASED APPROACHES TO 669 00:27:45,920 --> 00:27:48,000 IMPROVE PHYSICAL AND COGNITIVE 670 00:27:48,000 --> 00:27:50,040 OUTCOMES AFTER ARDS. 671 00:27:50,040 --> 00:27:52,520 SO I WILL HAND IT OVER TO 672 00:27:52,520 --> 00:27:53,880 Dr. GIRARD. 673 00:27:53,880 --> 00:27:57,800 >>THANK YOU SO MUCH, DOCTOR 674 00:27:57,800 --> 00:27:58,400 HOUGH. 675 00:27:58,400 --> 00:27:58,960 NEXT SLIDE, PLEASE. 676 00:27:58,960 --> 00:28:00,440 I DON'T HAVE A WHOLE LOT MORE 677 00:28:00,440 --> 00:28:01,880 TO ADD BUT I WANT TO TIE 678 00:28:01,880 --> 00:28:03,720 TOGETHER WHAT YOU SEE ON THE 679 00:28:03,720 --> 00:28:06,880 AGENDA FOR THE NEXT TWO DAYS' 680 00:28:06,880 --> 00:28:08,240 PROGRAMS FROM WHAT YOU HAVE 681 00:28:08,240 --> 00:28:11,120 HEARD FROM DOCTOR HOUGH SO FAR 682 00:28:11,120 --> 00:28:12,600 AND A GOOD PLACE TO START IS 683 00:28:12,600 --> 00:28:14,520 TO LOOK AT THE RESEARCH 684 00:28:14,520 --> 00:28:14,880 SPECTRUM. 685 00:28:14,880 --> 00:28:21,920 ALL OF US ARE FAMILIAR WITH 686 00:28:21,920 --> 00:28:24,880 THE CLINICAL PROCEDURES AT THE 687 00:28:24,880 --> 00:28:26,840 BEDSIDE AND NHLBI HAS THEIR 688 00:28:26,840 --> 00:28:27,960 OWN LINKS FOR THIS THAT YOU 689 00:28:27,960 --> 00:28:29,520 CAN SEE AT THE BOTTOM OF THE 690 00:28:29,520 --> 00:28:29,880 SLIDE. 691 00:28:29,880 --> 00:28:31,480 WHAT WE WANT TO ACCOMPLISH FOR 692 00:28:31,480 --> 00:28:33,760 THIS CONFERENCE OR WORKSHOP IS 693 00:28:33,760 --> 00:28:37,840 NOT ONLY TO HIGHLIGHT NEW 694 00:28:37,840 --> 00:28:40,040 ADVANCES AND KNOWLEDGE GAPS AS 695 00:28:40,040 --> 00:28:42,840 THE BENCH AND ALSO AT THE 696 00:28:42,840 --> 00:28:44,000 BEDSIDE BUT ALSO BRING THEM 697 00:28:44,000 --> 00:28:46,960 TOGETHER AND WE HAVE TRIED IN 698 00:28:46,960 --> 00:28:49,400 A STRATEGIC WAY TO GATHER SO 699 00:28:49,400 --> 00:28:51,480 MANY MODERATORS, PRESENTERS 700 00:28:51,480 --> 00:28:53,520 AND PARTICIPANTS THAT SPAN 701 00:28:53,520 --> 00:28:54,120 THIS RESEARCH SPECTRUM. 702 00:28:54,120 --> 00:28:58,160 AND WE WANT TO DO SO IN A WAY 703 00:28:58,160 --> 00:28:59,520 THAT WILL EMPHASIZE THE FACT 704 00:28:59,520 --> 00:29:04,600 THAT WE HAVE TO WORK TOGETHER. 705 00:29:04,600 --> 00:29:06,760 THE CONVERSATION CAN'T JUST BE 706 00:29:06,760 --> 00:29:08,480 WITHIN THE REALM OF BASIC 707 00:29:08,480 --> 00:29:10,320 SCIENCE OR WITHIN THE REALM OF 708 00:29:10,320 --> 00:29:12,840 CLINICAL AND WILL 709 00:29:12,840 --> 00:29:13,560 TRANSLATIONAL SCIENCE, BUT IT 710 00:29:13,560 --> 00:29:15,320 HAS TO BE ALL OF US TALKING 711 00:29:15,320 --> 00:29:15,680 TOGETHER. 712 00:29:15,680 --> 00:29:17,400 SO YOU WILL SEE TOMORROW, FOR 713 00:29:17,400 --> 00:29:18,960 EXAMPLE, WHEN WE GET TO THE 714 00:29:18,960 --> 00:29:20,760 POINT AT THE END OF THE 715 00:29:20,760 --> 00:29:23,680 WORKSHOP WHERE WE HAVE THE 716 00:29:23,680 --> 00:29:26,320 BREAKOUT ROOMS, THAT WE 717 00:29:26,320 --> 00:29:27,560 VERYING TENSIONALLY CREATED 718 00:29:27,560 --> 00:29:31,320 BREAKOUT ROOMS THAT WILL 719 00:29:31,320 --> 00:29:34,280 FACILITATE A MIXTURE OF THE 720 00:29:34,280 --> 00:29:36,840 FULL SPECTRUM FROM BASIC TO 721 00:29:36,840 --> 00:29:37,880 TRANSLATIONAL TO CLINICAL 722 00:29:37,880 --> 00:29:39,040 SCIENCE AND OTHER STAKEHOLDERS 723 00:29:39,040 --> 00:29:42,800 SO THAT WE CAN WORK ON THIS 724 00:29:42,800 --> 00:29:43,160 TOGETHER. 725 00:29:43,160 --> 00:29:44,800 AND WE KNOW THIS CAN BE 726 00:29:44,800 --> 00:29:45,240 ACCOMPLISHED. 727 00:29:45,240 --> 00:29:48,720 WE KNOW THIS CAN BE DONE IN 728 00:29:48,720 --> 00:29:50,800 MANY OTHER AREAS OF MEDICINE 729 00:29:50,800 --> 00:29:52,040 BUT ALSO ARDS. 730 00:29:52,040 --> 00:29:54,760 IF YOU WILL GO TO THE NEXT 731 00:29:54,760 --> 00:29:56,480 SLIDE, JUST AN EXAMPLE, WE 732 00:29:56,480 --> 00:29:58,960 HAVE TALKED A LOT HOW WE 733 00:29:58,960 --> 00:30:00,920 HAVEN'T MADE MUCH PROGRESS IN 734 00:30:00,920 --> 00:30:01,960 TERMS OF TRANSLATING 735 00:30:01,960 --> 00:30:03,560 DISCOVERIES TO DIFFERENCES IN 736 00:30:03,560 --> 00:30:06,080 OUTCOMES IN TERMS OF BRAIN AND 737 00:30:06,080 --> 00:30:07,000 MUSCLE DYSFUNCTION AFTER ARDS 738 00:30:07,000 --> 00:30:10,400 BUT WE DON'T HAVE TO LOOK VERY 739 00:30:10,400 --> 00:30:13,520 FAR TO SEE AN EXAMPLE OF BENCH 740 00:30:13,520 --> 00:30:14,880 TO BEDSIDESTEPS IN ARDS. 741 00:30:14,880 --> 00:30:17,680 SO YOU GO BACK TO THE 80s, 742 00:30:17,680 --> 00:30:20,080 FOR EXAMPLE, IN THIS PAPER, 743 00:30:20,080 --> 00:30:22,160 WHERE THE STUDY IS DONE IN 744 00:30:22,160 --> 00:30:28,160 RATS AND SUGGESTED INCREASED 745 00:30:28,160 --> 00:30:29,120 INFLATION PRESSURES WERE 746 00:30:29,120 --> 00:30:32,960 HARMFUL TO THOSE IN THE ANIMAL 747 00:30:32,960 --> 00:30:34,440 MODELS AND CONVERSELY THAT WAS 748 00:30:34,440 --> 00:30:36,640 TRANSLATED THEN TO WORK DONE 749 00:30:36,640 --> 00:30:39,120 IN LARGER ANIMAL MODELS AND 750 00:30:39,120 --> 00:30:40,240 THEN ADVANCED AGAIN. 751 00:30:40,240 --> 00:30:44,440 EVENTUALLY THAT WAS BROUGHT TO 752 00:30:44,440 --> 00:30:46,840 THE BEDSIDE IN A LARGE 753 00:30:46,840 --> 00:30:48,240 POSITIVE CLINICAL TRIAL THAT 754 00:30:48,240 --> 00:30:49,520 ULTIMATELY MADE THE DIFFERENCE 755 00:30:49,520 --> 00:30:52,920 IN HOW PATIENTS WERE CARED FOR 756 00:30:52,920 --> 00:30:54,320 AND THEIR OUTCOMES. 757 00:30:54,320 --> 00:30:54,920 ADVANCE AGAIN, PLEASE. 758 00:30:54,920 --> 00:30:58,240 AT THE SAME TIME AS DOCTOR 759 00:30:58,240 --> 00:31:00,600 HOUGH MENTIONED, A NUMBER 760 00:31:00,600 --> 00:31:03,040 OF -- ACTUALLY MANY DIFFERENT 761 00:31:03,040 --> 00:31:04,200 INTERVENTIONS HAVE BEEN 762 00:31:04,200 --> 00:31:08,600 STUDIED IN EFFORTS TO IMPROVE 763 00:31:08,600 --> 00:31:10,520 LONG-TERM OUTCOMES FOR 764 00:31:10,520 --> 00:31:12,600 PATIENTS WHO SUFFER ARDS OR 765 00:31:12,600 --> 00:31:13,760 SOME OTHER CRITICAL SYNDROME. 766 00:31:13,760 --> 00:31:17,960 AND I WANT TO MENTION THAT 767 00:31:17,960 --> 00:31:19,760 ARDS IS SPONSORING THIS 768 00:31:19,760 --> 00:31:21,680 WORKSHOP AS WELL BECAUSE THEY 769 00:31:21,680 --> 00:31:23,000 RECOGNIZE HOW IMPORTANT THE 770 00:31:23,000 --> 00:31:26,360 KNOWLEDGE GAGED FROM THE STUDY 771 00:31:26,360 --> 00:31:28,040 OF ARDS IS TO SEPSIS AND THERE 772 00:31:28,040 --> 00:31:32,280 IS A LOT OF CRITICAL OVERLAP 773 00:31:32,280 --> 00:31:33,000 FOR THE SYNDROMES. 774 00:31:33,000 --> 00:31:35,160 SO WHAT WE WILL BE FOCUSING ON 775 00:31:35,160 --> 00:31:37,520 THE NEXT FEW DAYS IS NOT ONLY 776 00:31:37,520 --> 00:31:41,760 RELIED TO ARDS BUT SEPSIS AND 777 00:31:41,760 --> 00:31:42,520 OTHER CLINICAL SYNDROMES. 778 00:31:42,520 --> 00:31:45,760 BUT WHAT WE HAVE SEEN IS THE 779 00:31:45,760 --> 00:31:47,640 STUDIES AND ADVANCES, TRIALS 780 00:31:47,640 --> 00:31:51,000 IN THESE AREAS THAT DETERMINED 781 00:31:51,000 --> 00:31:52,360 LONG-TERM OUTCOMES HAVEN'T 782 00:31:52,360 --> 00:31:54,520 ALWAYS NECESSARILY BEEN 783 00:31:54,520 --> 00:31:56,680 INFORMED BY MECHANISMS AND 784 00:31:56,680 --> 00:31:58,600 UNDERSTANDING OF MECHANISMS. 785 00:31:58,600 --> 00:32:00,040 SO ADVANCE, PLEASE. 786 00:32:00,040 --> 00:32:01,920 WE MAY SEE SOME POSITIVE 787 00:32:01,920 --> 00:32:03,640 STUDIES LIKE THIS ONE BUT 788 00:32:03,640 --> 00:32:04,960 STILL NOT EXACTLY SURE WHY. 789 00:32:04,960 --> 00:32:07,600 WHAT IS THE MECHANISM OR 790 00:32:07,600 --> 00:32:08,560 MECHANISMS THAT UNDERLIE THE 791 00:32:08,560 --> 00:32:10,040 DIFFERENCE IN THE OUTCOME THAT 792 00:32:10,040 --> 00:32:12,480 A FEW POSITIVE TRIALS HAVE 793 00:32:12,480 --> 00:32:13,080 HAD? 794 00:32:13,080 --> 00:32:14,480 THOSE ARE REALLY IMPORTANT 795 00:32:14,480 --> 00:32:15,720 QUESTIONS BECAUSE IN ORDER FOR 796 00:32:15,720 --> 00:32:18,640 US TO TRANSLATE THIS TO OTHER 797 00:32:18,640 --> 00:32:20,840 EFFECTIVE INTERVENTIONS AND TO 798 00:32:20,840 --> 00:32:23,000 REALLY IMPROVE OUTCOMES FOR 799 00:32:23,000 --> 00:32:24,280 PATIENTS LONG-TERM AS THEY 800 00:32:24,280 --> 00:32:26,920 RECOVER FROM ARDS, SEPSIS AND 801 00:32:26,920 --> 00:32:27,880 OTHER CRITICAL ILLNESS 802 00:32:27,880 --> 00:32:29,200 SYNDROME, WE HAVE TO 803 00:32:29,200 --> 00:32:31,280 UNDERSTAND THE FULL SPECTRUM 804 00:32:31,280 --> 00:32:33,000 FROM BENCH TO BEDSIDE. 805 00:32:33,000 --> 00:32:34,720 SO THAT IS MY LAST SLIDE AND I 806 00:32:34,720 --> 00:32:38,160 THINK I WILL TURN IT BACK OVER 807 00:32:38,160 --> 00:32:41,720 TO Dr. HOUGH TO INTRODUCE 808 00:32:41,720 --> 00:32:43,200 THE MODERATORS FOR THE SESSION 809 00:32:43,200 --> 00:32:45,680 AND THANK YOU ALL FOR 810 00:32:45,680 --> 00:32:46,120 PARTICIPATING. 811 00:32:46,120 --> 00:32:47,200 >>Dr. GIRARD, THANK YOU AND 812 00:32:47,200 --> 00:32:48,560 THANK YOU FOR NICELY 813 00:32:48,560 --> 00:32:49,640 PROGRAMSING US FOR THE 814 00:32:49,640 --> 00:32:51,000 DISCUSSIONS WE WILL BE HAVING 815 00:32:51,000 --> 00:32:53,000 OVER THE NEXT TWO DAYS. 816 00:32:53,000 --> 00:32:55,040 SO LET'S LAUNCH RIGHT INTO 817 00:32:55,040 --> 00:32:55,560 SESSION 1. 818 00:32:55,560 --> 00:32:57,480 SESSION 1 WILL BE RIGHT SMACK 819 00:32:57,480 --> 00:33:00,800 IN THE MIDDLE OF THAT DIAGRAM, 820 00:33:00,800 --> 00:33:03,000 FROM BENCH TO BEDSIDE AND 821 00:33:03,000 --> 00:33:04,920 INTERVENTION AND BACK THAT 822 00:33:04,920 --> 00:33:08,000 Dr. GIRARD JUST SHOWED US, 823 00:33:08,000 --> 00:33:10,880 FOCUSING ON THE CLINICAL 824 00:33:10,880 --> 00:33:11,560 PRESENTATION, RIGOROUS 825 00:33:11,560 --> 00:33:12,400 MEASUREMENT AND SOCIAL 826 00:33:12,400 --> 00:33:14,000 DETERMINANTS OF BRAIN AND 827 00:33:14,000 --> 00:33:16,840 MUSCLE DYSFUNCTION IN ARDS 828 00:33:16,840 --> 00:33:17,200 SURVIVORS. 829 00:33:17,200 --> 00:33:19,840 SO TO LEAD US INTO THE NEXT 830 00:33:19,840 --> 00:33:21,200 SESSION, I WOULD INTRODUCE 831 00:33:21,200 --> 00:33:23,200 FRIENDS AND COLLEAGUES OF 832 00:33:23,200 --> 00:33:27,160 MINE, FIRST Dr. LAUREN 833 00:33:27,160 --> 00:33:30,720 FERRANTE WHO IS A PHYSICIANS 834 00:33:30,720 --> 00:33:33,160 IN PULMONARY CARE AT YALE 835 00:33:33,160 --> 00:33:35,560 UNIVERSITY. 836 00:33:35,560 --> 00:33:38,320 Dr. FE RRANTE HAS BEEN SPE 837 00:33:38,320 --> 00:33:41,120 INTERSECTION OF PUMMOLOGY AND 838 00:33:41,120 --> 00:33:45,600 CRITICAL CARE AND THAT 839 00:33:45,600 --> 00:33:50,160 KNOWLEDGE OF THE OUTCOMES, AND 840 00:33:50,160 --> 00:33:54,160 HAS TAUGHT US A LOT HOW THE 841 00:33:54,160 --> 00:33:56,440 BASELINE PLAYS INTO THE KEY 842 00:33:56,440 --> 00:33:57,040 ILLNESS AS WELL. 843 00:33:57,040 --> 00:34:03,200 THEN I WOULD LIKE TO INTRODUCE 844 00:34:03,200 --> 00:34:05,080 Dr. IWASHYNA FROM HOPKINS 845 00:34:05,080 --> 00:34:07,600 UNIVERSITY, AN EXPERT IN 846 00:34:07,600 --> 00:34:08,760 CLINICAL EPIDEMIOLOGY AND 847 00:34:08,760 --> 00:34:10,040 HEALTH SERVICES RESEARCH AND 848 00:34:10,040 --> 00:34:12,800 ONE OF THE FEW CLINICAL CARE 849 00:34:12,800 --> 00:34:16,360 DOCS I KNOW WHO HAS ADVANCED 850 00:34:16,360 --> 00:34:17,400 TRAINING IN SOCIOLOGY AND I 851 00:34:17,400 --> 00:34:21,920 THINK THIS SHOWS THE WAY THAT 852 00:34:21,920 --> 00:34:23,960 DOCTOR IWASHYNA TACKLES THE 853 00:34:23,960 --> 00:34:25,320 RECOVERY AND UNDERSTANDING THE 854 00:34:25,320 --> 00:34:29,440 PATIENTS AND THEIR FAMILIES 855 00:34:29,440 --> 00:34:32,320 AFTER CRITICAL ILLNESS SO 856 00:34:32,320 --> 00:34:35,560 DOCTORS FE RRANTE AND 857 00:34:35,560 --> 00:34:37,240 IWASHYNA, TAKE IT AWAY. 858 00:34:37,240 --> 00:34:43,720 >>THANK YOU SO MUCH, TERRI, 859 00:34:43,720 --> 00:34:45,560 WE'RE PLEASED TO MODERATE THIS 860 00:34:45,560 --> 00:34:47,080 SESSION AND DELIGHTED TO 861 00:34:47,080 --> 00:34:53,880 INTRODUCE OUR FIRST SPEAKER, 862 00:34:53,880 --> 00:34:55,600 Dr. CARLA SEVIN FROM 863 00:34:55,600 --> 00:34:56,400 NATIONALVILLE, TENNESSEE. 864 00:34:56,400 --> 00:35:01,640 IN ADDITION TO CARING FOR 865 00:35:01,640 --> 00:35:06,960 CRITICALLY ILL PATIENTS 866 00:35:06,960 --> 00:35:09,760 INCLUDING THOSE WITH COVID. 867 00:35:09,760 --> 00:35:16,680 AND IN 2017 STARTS A THRIVE 868 00:35:16,680 --> 00:35:20,320 CAB -- COLLABORATIVE. 869 00:35:20,320 --> 00:35:26,120 HE NOW LEADS A CLINICAL GROUP 870 00:35:26,120 --> 00:35:28,320 AND WELCOME Dr. SEVIN, 871 00:35:28,320 --> 00:35:29,520 THANKS FOR BEING WITH US 872 00:35:29,520 --> 00:35:29,800 TODAY. 873 00:35:29,800 --> 00:35:33,600 >>THANK YOU FOR THAT 874 00:35:33,600 --> 00:35:36,320 FANTASTIC INTRODUCTION AND 875 00:35:36,320 --> 00:35:38,360 PLEASED TO SEE SO MANY NAMES 876 00:35:38,360 --> 00:35:44,400 AND FACES AND LOOKING FORWARD 877 00:35:44,400 --> 00:35:45,720 TO THE SESSION. 878 00:35:45,720 --> 00:35:49,920 IF THE PERSON IN CHARGE OF THE 879 00:35:49,920 --> 00:35:51,880 SLIDES WILL NOTE I HAVE SOME 880 00:35:51,880 --> 00:35:54,360 SLIDES AT THE END OF MY TALK 881 00:35:54,360 --> 00:35:57,160 AND WILL TALK IN A STREAM OF 882 00:35:57,160 --> 00:36:03,200 CONSCIOUSNESS AS I TEND TO DO 883 00:36:03,200 --> 00:36:08,120 BUT HERE ARE MY DISCLOSURES. 884 00:36:08,120 --> 00:36:10,280 MY MAJOR DISCLOSURE IS I AM 885 00:36:10,280 --> 00:36:11,120 VERY PASSIONATE ABOUT THIS 886 00:36:11,120 --> 00:36:12,720 WORK THAT COMES FROM WORKING 887 00:36:12,720 --> 00:36:15,440 WITH PATIENTS AND FAMILIES AT 888 00:36:15,440 --> 00:36:22,360 THE BEDSIDE SO IF I EDGE INTO 889 00:36:22,360 --> 00:36:24,120 POSSIBLETIZING WITH POLICIES, 890 00:36:24,120 --> 00:36:24,920 NEXT SLIDE, PLEASE. 891 00:36:24,920 --> 00:36:26,840 I BECAME INTERESTED IN THIS 892 00:36:26,840 --> 00:36:29,520 AREA OF MEDICINE WHEN I WAS A 893 00:36:29,520 --> 00:36:32,720 RESIDENT AND FELLOW HERE AT 894 00:36:32,720 --> 00:36:33,160 VANDERBILT. 895 00:36:33,160 --> 00:36:34,280 TIM GIRARD WAS ONE OF MY 896 00:36:34,280 --> 00:36:37,360 FELLOWS WHEN I WAS A LOCALLY 897 00:36:37,360 --> 00:36:40,360 INTERN AND I WAS FORCED TO SAY 898 00:36:40,360 --> 00:36:42,400 I DON'T KNOW MANY TIMES IN A 899 00:36:42,400 --> 00:36:45,240 ROW IN THAT ROTATION WHICH WAS 900 00:36:45,240 --> 00:36:46,080 A VERY FRUSTRATING EXPERIENCE 901 00:36:46,080 --> 00:36:46,600 FOR ME. 902 00:36:46,600 --> 00:36:50,240 AND WHEN I CAME ON TO FACULTY, 903 00:36:50,240 --> 00:36:52,880 WE STARTED A POST BEDSIDE 904 00:36:52,880 --> 00:36:55,920 CLINIC AND I NOW HAVE TO SAY I 905 00:36:55,920 --> 00:36:58,000 DON'T KNOW MANY TIMES STILL 906 00:36:58,000 --> 00:37:00,960 BUT IT DOESN'T BOTHER ME AS 907 00:37:00,960 --> 00:37:03,440 MUCH BECAUSE EVERY TIME WE SAY 908 00:37:03,440 --> 00:37:06,840 I DON'T KNOW, IT IS A PLACE TO 909 00:37:06,840 --> 00:37:11,720 TARGET TO LEARN ABOUT FOR 910 00:37:11,720 --> 00:37:12,560 INTERVENTION. 911 00:37:12,560 --> 00:37:14,600 SO A COUPLE OF SLIDES TO BRING 912 00:37:14,600 --> 00:37:16,240 TO TOP OF MIND WHY WE'RE HERE 913 00:37:16,240 --> 00:37:17,960 AND WHAT WE WANT TO BUILD ON 914 00:37:17,960 --> 00:37:19,600 TODAY AND THEN TALK ABOUT THE 915 00:37:19,600 --> 00:37:20,720 CLINICAL PRESENTATION OF BRAIN 916 00:37:20,720 --> 00:37:22,120 AND MUSCLE PROBLEMS WE SEE 917 00:37:22,120 --> 00:37:24,000 WHEN PATIENTS COME INTO THE 918 00:37:24,000 --> 00:37:24,320 CLINIC. 919 00:37:24,320 --> 00:37:27,760 SO BY NOW YOU HAVE HEARD ABOUT 920 00:37:27,760 --> 00:37:29,320 THE POST-INTENSIVE CARE 921 00:37:29,320 --> 00:37:32,480 SYNDROME, I HOPE, AND Dr. 922 00:37:32,480 --> 00:37:34,320 HARRELL TALKED ABOUT IT IN HER 923 00:37:34,320 --> 00:37:36,280 TALK, IF YOU COULD CLICK 924 00:37:36,280 --> 00:37:38,560 THROUGH THE NEXT FEW BUBBLES, 925 00:37:38,560 --> 00:37:41,000 HERE, WHOEVER IS ADVANCING THE 926 00:37:41,000 --> 00:37:41,360 SLIDES. 927 00:37:41,360 --> 00:37:42,520 KEEP GOING. 928 00:37:42,520 --> 00:37:44,400 SO THE POST-INTENSIVE CARE 929 00:37:44,400 --> 00:37:47,600 SYNDROME WAS A TERM REALLY 930 00:37:47,600 --> 00:37:49,000 DEVELOPED IN 2012 AND WILL BE 931 00:37:49,000 --> 00:37:51,600 SHARED WITH US TODAY TO SORT 932 00:37:51,600 --> 00:37:54,440 OF PUT A NAME TO THIS 933 00:37:54,440 --> 00:37:55,280 CONSTELLATION OF PROBLEMS WE 934 00:37:55,280 --> 00:37:57,920 WERE SEEING IN PATIENTS WHO 935 00:37:57,920 --> 00:38:00,880 SURVIVED CRITICAL ILLNESS AND 936 00:38:00,880 --> 00:38:08,640 IT IS MARKED BY MENTAL 937 00:38:08,640 --> 00:38:09,640 IMPAIRMENT, FAMILY HEALTH 938 00:38:09,640 --> 00:38:11,960 PROBLEMS AND HIGH BURDEN OF 939 00:38:11,960 --> 00:38:13,160 CHRONIC HEALTH CONDITIONS. 940 00:38:13,160 --> 00:38:14,000 NEXT SLIDE, PLEASE. 941 00:38:14,000 --> 00:38:16,200 WE WILL HEAR IN MORE SPECIFIC 942 00:38:16,200 --> 00:38:19,680 DETAIL ABOUT THE PHYSICAL 943 00:38:19,680 --> 00:38:22,000 SEQUELAE WHICH ARE 944 00:38:22,000 --> 00:38:22,440 LONG-LASTING. 945 00:38:22,440 --> 00:38:23,720 NEXT SLIDE. 946 00:38:23,720 --> 00:38:26,120 THE COGNITIVE IMPAIRMENTS THAT 947 00:38:26,120 --> 00:38:29,680 ARE REALLY IMPACTFUL FOR 948 00:38:29,680 --> 00:38:31,680 PATIENTS AND ARE NOT WELL 949 00:38:31,680 --> 00:38:34,160 ADDRESSED IN OUR HEALTH 950 00:38:34,160 --> 00:38:34,720 SYSTEM. 951 00:38:34,720 --> 00:38:39,040 THIS SHOWS THE GLOBAL 952 00:38:39,040 --> 00:38:41,160 COGNITION DECREASED IN 953 00:38:41,160 --> 00:38:42,760 SURVIVORS WHO SURVIVED 954 00:38:42,760 --> 00:38:44,360 CRITICAL AIRNESS, THE COLUMN 955 00:38:44,360 --> 00:38:47,760 ON THE LEFT ARE PATIENTS UNDER 956 00:38:47,760 --> 00:38:50,040 49 YEARS OLD SO EVEN YOUNGER 957 00:38:50,040 --> 00:38:51,520 PATIENTS RAILROAD NOT 958 00:38:51,520 --> 00:38:53,680 PROTECTED FROM COGNITIVE 959 00:38:53,680 --> 00:38:54,160 ILLNESS. 960 00:38:54,160 --> 00:38:56,840 AND POSTTRAUMATIC STRESS AS 961 00:38:56,840 --> 00:39:00,720 Dr. HARRELL MENTIONED HAS A 962 00:39:00,720 --> 00:39:03,160 HUGE IMPACT AFTER CRITICAL 963 00:39:03,160 --> 00:39:03,520 ILLNESS. 964 00:39:03,520 --> 00:39:05,880 Dr. HARRELL AND I DID NOT 965 00:39:05,880 --> 00:39:07,280 COORDINATE OUR TALKS BEFORE 966 00:39:07,280 --> 00:39:13,040 THIS SESSION BUT YOU WILL BE 967 00:39:13,040 --> 00:39:15,600 SURPRISED TO HEAR BECAUSE HER 968 00:39:15,600 --> 00:39:21,240 DESCRIPTION IS SO ACCURATE AND 969 00:39:21,240 --> 00:39:26,000 A COMMON OUTCOME WE SEE, VERY 970 00:39:26,000 --> 00:39:28,400 CRITICAL ILLNESS AND PATIENTS 971 00:39:28,400 --> 00:39:31,880 ARE DEALING WITH SIMILAR 972 00:39:31,880 --> 00:39:32,240 PROBLEMS. 973 00:39:32,240 --> 00:39:33,520 POSTTRAUMATIC STRESS IS 974 00:39:33,520 --> 00:39:35,240 ANOTHER SYMPTOM WE DON'T 975 00:39:35,240 --> 00:39:37,280 SCREEN FOR AFTER CRITICAL 976 00:39:37,280 --> 00:39:37,640 ILLNESS. 977 00:39:37,640 --> 00:39:40,480 THIS IS A GRAPH OF PATIENTS 978 00:39:40,480 --> 00:39:41,520 WHO SUFFERED CARDIAC ARREST 979 00:39:41,520 --> 00:39:47,760 SPECIFICALLY AND THOSE WHO HAD 980 00:39:47,760 --> 00:39:48,760 POSTTRAUMATIC STRESS SYMPTOMS 981 00:39:48,760 --> 00:39:51,120 IN THE RED LINES COMPARED TO 982 00:39:51,120 --> 00:39:54,080 THOSE WHO DID NOT IN THE BLUE 983 00:39:54,080 --> 00:40:03,400 WERE MORE THAN LIKELY TO DIE A 984 00:40:03,400 --> 00:40:06,560 YEAR AFTER WARDS SO IT IS 985 00:40:06,560 --> 00:40:09,200 SOMETHING WE NEED TO LOOK FOR. 986 00:40:09,200 --> 00:40:12,480 AND THEN AS CONSIDER HARRELL 987 00:40:12,480 --> 00:40:15,240 MENTIONED, SUICIDE AND SELF 988 00:40:15,240 --> 00:40:20,760 HARM UNDER ADULT SURVIVORS OF 989 00:40:20,760 --> 00:40:23,760 CRITICAL ILLNESS, SOMETHING WE 990 00:40:23,760 --> 00:40:26,320 SEE IN MANY CRITICALLY-ILL 991 00:40:26,320 --> 00:40:26,680 PATIENTS. 992 00:40:26,680 --> 00:40:27,120 NEXT SLIDE. 993 00:40:27,120 --> 00:40:28,640 SO CRITICAL ILLNESS IS REALLY 994 00:40:28,640 --> 00:40:30,800 THE ONSET OF A CHRONIC 995 00:40:30,800 --> 00:40:31,160 ILLNESS. 996 00:40:31,160 --> 00:40:32,640 I THINK MANY OF OUR PATIENTS 997 00:40:32,640 --> 00:40:35,080 AND ARE US THINK OF SURVIVING 998 00:40:35,080 --> 00:40:36,920 THE ICU AS THE END OF 999 00:40:36,920 --> 00:40:38,520 SOMETHING BUT IN FACT IT IS 1000 00:40:38,520 --> 00:40:39,600 THE BEGINNING OF ANOTHER THING 1001 00:40:39,600 --> 00:40:43,000 AND THIS IS A REALLY PROLONGED 1002 00:40:43,000 --> 00:40:43,480 CHRONIC ILLNESS. 1003 00:40:43,480 --> 00:40:45,520 THIS IS ONE OF OUR PATIENTS 1004 00:40:45,520 --> 00:40:47,600 WHO CAME TO THE CLINIC WITH 1005 00:40:47,600 --> 00:40:50,840 HIS PARTNER AFTER A 4-MONTH 1006 00:40:50,840 --> 00:40:52,320 ICU STAY AND I THINK YOU CAN 1007 00:40:52,320 --> 00:40:54,400 APPRECIATE THIS IS A YOUNG 1008 00:40:54,400 --> 00:40:56,840 PERSON WHO IS STILL VERY 1009 00:40:56,840 --> 00:40:57,640 IMPAIRED DESPITE BEING WELL 1010 00:40:57,640 --> 00:41:01,960 ENOUGH TO LEAVE THE HOSPITAL. 1011 00:41:01,960 --> 00:41:02,880 NEXT SLIDE, PLEASE. 1012 00:41:02,880 --> 00:41:05,720 AND IN FACT WE HAVE SOME DATA 1013 00:41:05,720 --> 00:41:07,640 THAT SHOWS EVEN THE THINGS WE 1014 00:41:07,640 --> 00:41:11,560 TRADITIONALLY THINK OF AS 1015 00:41:11,560 --> 00:41:21,200 CHRONIC ILLNESSES, COPD, 1016 00:41:21,200 --> 00:41:23,600 DIABETES, HYPER LIPIDEMIA ARE 1017 00:41:23,600 --> 00:41:25,760 MORE PREVALENT THAN THOSE 1018 00:41:25,760 --> 00:41:27,320 HOSPITALIZED FOR OTHER 1019 00:41:27,320 --> 00:41:27,640 REASONS. 1020 00:41:27,640 --> 00:41:28,040 NEXT SLIDE. 1021 00:41:28,040 --> 00:41:30,480 THIS IS A VERY TYPICAL 1022 00:41:30,480 --> 00:41:33,400 PRESENTATION THAT WE SEE IN 1023 00:41:33,400 --> 00:41:35,000 OUR CLINIC. 1024 00:41:35,000 --> 00:41:36,520 IF YOU COULD CLICK THROUGH THE 1025 00:41:36,520 --> 00:41:39,000 TEXT AREA. 1026 00:41:39,000 --> 00:41:41,200 A 37-YEAR-OLD WOMAN WITH 1027 00:41:41,200 --> 00:41:51,800 CRITICAL ILLNESS DUE TO H1N1, 1028 00:41:57,760 --> 00:42:06,000 TRANSFERRED TO LTAC, A VENT, 1029 00:42:06,000 --> 00:42:07,960 TRACH, PARALYSIS, DELIRIUM, 1030 00:42:07,960 --> 00:42:10,720 DVT, AND UNFORTUNATELY THE 1031 00:42:10,720 --> 00:42:13,560 PATIENT WAS UNINSURED SO WE 1032 00:42:13,560 --> 00:42:15,520 HAD TO DO SOME WORK TO GET HER 1033 00:42:15,520 --> 00:42:16,880 TO THE RIGHT PLACE. 1034 00:42:16,880 --> 00:42:20,840 I WANTED TO GET HER 1035 00:42:20,840 --> 00:42:22,760 TRANSFERRED WHERE SHE COULD DO 1036 00:42:22,760 --> 00:42:26,080 THREE HOURS OF PHYSICAL 1037 00:42:26,080 --> 00:42:27,640 THERAPY PER DAY. 1038 00:42:27,640 --> 00:42:28,560 SHE WAS SUFFERING PARALYSIS 1039 00:42:28,560 --> 00:42:31,720 AND I MADE A DEAL WITH THE 1040 00:42:31,720 --> 00:42:35,000 DEVIL TO LET HER GO TO LTAC A 1041 00:42:35,000 --> 00:42:37,600 FEW DAYS UNTIL SHE COULD THEN 1042 00:42:37,600 --> 00:42:38,520 TRANSITION FOR REHAB. 1043 00:42:38,520 --> 00:42:40,360 I GOT A MESSAGE A FEW DAYS 1044 00:42:40,360 --> 00:42:42,000 LATER THAT SHE COULD WALK NOW 1045 00:42:42,000 --> 00:42:44,520 AND DIDN'T NEED TO GO TO 1046 00:42:44,520 --> 00:42:46,880 IN-PATIENT REHAB AND SAW HER 1047 00:42:46,880 --> 00:42:50,280 IN CLINIC FIVE WEEKS POST 1048 00:42:50,280 --> 00:42:51,000 HOSPITAL DISCHARGE. 1049 00:42:51,000 --> 00:42:55,520 BUT SHE COULD NOT WALK, NEEDED 1050 00:42:55,520 --> 00:42:57,480 A THREE-PERSON ASSIST TO GET 1051 00:42:57,480 --> 00:43:01,200 UP OFF THE EXAM TABLE, HAD 1052 00:43:01,200 --> 00:43:04,080 FOOD DROP AND NO BRACES TO 1053 00:43:04,080 --> 00:43:08,520 HELP WITH ANYTHING WITH THAT, 1054 00:43:08,520 --> 00:43:11,960 MALNOURISHED WITH A 26-POUND 1055 00:43:11,960 --> 00:43:15,760 WEIGHT LOSS WHICH IS TYPICAL 1056 00:43:15,760 --> 00:43:17,000 AND HAIR LOSS WHICH IS 1057 00:43:17,000 --> 00:43:19,520 SOMETHING WE CAN TREAT WITH 1058 00:43:19,520 --> 00:43:19,880 EDUCATION. 1059 00:43:19,880 --> 00:43:26,360 SHE WAS BACK ON LOVANOX, SHE 1060 00:43:26,360 --> 00:43:27,600 WAS HAVING HYPERTENSIVE 1061 00:43:27,600 --> 00:43:34,000 EPISODES ON A BETA BLOCKER 1062 00:43:34,000 --> 00:43:35,840 WITH SYNCOPE, DIARRHEA WAS 1063 00:43:35,840 --> 00:43:37,560 PROBABLY A SIDE EFFECT. 1064 00:43:37,560 --> 00:43:39,320 WANTED TO RETURN TO WORK, 1065 00:43:39,320 --> 00:43:44,360 COULD NOT DRIVE AND HER TRACH 1066 00:43:44,360 --> 00:43:47,360 WAS CANULATES SO THAT WAS THE 1067 00:43:47,360 --> 00:43:49,480 ONE THING WE DIDN'T HAVE TO 1068 00:43:49,480 --> 00:43:50,840 WORK ON. 1069 00:43:50,840 --> 00:43:51,800 NEXT SLIDE. 1070 00:43:51,800 --> 00:43:58,120 SO THE NECK SPEAKER, I AM VERY 1071 00:43:58,120 --> 00:44:00,040 LUCKY TO WORK WITH HIM EVERY 1072 00:44:00,040 --> 00:44:02,680 WEEK AND HE DID A TYPICAL 1073 00:44:02,680 --> 00:44:04,320 COGNITIVE EVALUATION FOR THIS 1074 00:44:04,320 --> 00:44:06,960 PATIENT INCLUDING A M O CA 1075 00:44:06,960 --> 00:44:11,320 WHICH WAS SIGNIFICANTLY 1076 00:44:11,320 --> 00:44:14,840 IMPAIRED, MULTIPLE ERRORS ON A 1077 00:44:14,840 --> 00:44:17,000 SERIAL 7'S TASK AND SIMILAR 1078 00:44:17,000 --> 00:44:18,160 TESTIFIES AND HIS CONCLUSION 1079 00:44:18,160 --> 00:44:21,560 WAS ALTHOUGH HER JOB WAS NOT 1080 00:44:21,560 --> 00:44:22,440 TYPICALLY COGNITIVELY 1081 00:44:22,440 --> 00:44:23,400 DEMANDING, HER COGNITIVE 1082 00:44:23,400 --> 00:44:24,760 PROBLEMS WERE SO GREAT THAT 1083 00:44:24,760 --> 00:44:26,800 THEY WOULD LIKELY INTERFERE 1084 00:44:26,800 --> 00:44:28,400 WITH PER PERFORMANCE AND IN 1085 00:44:28,400 --> 00:44:29,680 FACT WERE NOT ABLE TO 1086 00:44:29,680 --> 00:44:32,520 RECOMMEND A RETURN TO WORK 1087 00:44:32,520 --> 00:44:33,680 TILL NINE MONTHS LATER WHEN 1088 00:44:33,680 --> 00:44:37,520 SHE HAD A TRIAL RETURN TO 1089 00:44:37,520 --> 00:44:37,840 WORK. 1090 00:44:37,840 --> 00:44:38,240 NEXT SLIDE. 1091 00:44:38,240 --> 00:44:40,760 SO THIS IS A TABLE FROM OUR 1092 00:44:40,760 --> 00:44:42,800 DESCRIPTION OF THE FIRST 1093 00:44:42,800 --> 00:44:44,200 6 PATIENTS WE SAW IN CLINIC 1094 00:44:44,200 --> 00:44:46,440 AND IF YOU CLICK THROUGH THE 1095 00:44:46,440 --> 00:44:49,040 RED BOXES, I WANT TO HIGHLIGHT 1096 00:44:49,040 --> 00:44:52,520 WE HAD MEANINGFUL COGNITIVE 1097 00:44:52,520 --> 00:44:53,840 IMPAIRMENT IN 64 PERCENT OF 1098 00:44:53,840 --> 00:44:55,240 THE PATIENTS WE SAW THERE. 1099 00:44:55,240 --> 00:44:58,560 WE DO A SIX-MINUTE WALK TO 1100 00:44:58,560 --> 00:45:03,320 LOOK FOR A CRITICAL AWARENESS, 1101 00:45:03,320 --> 00:45:04,040 NEUROPATHY, WHAT THEIR SPECIAL 1102 00:45:04,040 --> 00:45:05,360 NEEDS ARE AND MORE THAN A 1103 00:45:05,360 --> 00:45:08,440 QUALITY OF OUR PATIENTS WERE 1104 00:45:08,440 --> 00:45:10,720 NOT ABLE TO DO THE SIX-MINUTE 1105 00:45:10,720 --> 00:45:11,080 WALK. 1106 00:45:11,080 --> 00:45:12,360 THOSE ARE ALL PATIENTS WELL 1107 00:45:12,360 --> 00:45:16,000 ENOUGH TO GO HOME AND WELL 1108 00:45:16,000 --> 00:45:18,480 ENOUGH TO GET TO IN PERSON 1109 00:45:18,480 --> 00:45:20,480 CLINIC AND WERE NOT WELL 1110 00:45:20,480 --> 00:45:21,920 ENOUGH TO WALK. 1111 00:45:21,920 --> 00:45:24,480 MANY OF OUR PATIENTS, NOT 1112 00:45:24,480 --> 00:45:25,680 UNSURPRISINGLY, WERE NOT 1113 00:45:25,680 --> 00:45:27,600 DRIVING AND 65 PERCENT WHO HAD 1114 00:45:27,600 --> 00:45:28,560 BEEN PREVIOUSLY WORKING WERE 1115 00:45:28,560 --> 00:45:30,720 NOT ABLE TO RETURN TO WORK. 1116 00:45:30,720 --> 00:45:32,400 AND THE SECOND CITATION THERE 1117 00:45:32,400 --> 00:45:40,720 AT THE POT IS A METAANALYSIS 1118 00:45:40,720 --> 00:45:44,600 BY JOE McPEAKE SHOWING THIS 1119 00:45:44,600 --> 00:45:48,560 IS NOT UNIQUE AND 46 PERCENT 1120 00:45:48,560 --> 00:45:53,040 OF PATIENTS UNABLE TO RETURN 1121 00:45:53,040 --> 00:45:58,800 TO WORK SIX MONTHS AFTER THEIR 1122 00:45:58,800 --> 00:45:59,480 HOSPITAL STAY. 1123 00:45:59,480 --> 00:46:03,160 SO WE GET TO MEASURE WHAT ARE 1124 00:46:03,160 --> 00:46:04,880 YOU DOING, HOW DO YOU RESPOND 1125 00:46:04,880 --> 00:46:07,640 AND WE DON'T KNOW THE RESPONSE 1126 00:46:07,640 --> 00:46:09,600 OF WHAT ARE THE MOST 1127 00:46:09,600 --> 00:46:11,280 EFFICACIOUS THINGS TO DO FOR 1128 00:46:11,280 --> 00:46:14,040 THESE PATIENTS BUT ONE TOPIC 1129 00:46:14,040 --> 00:46:16,520 THAT HAS COME UP QUITE A BIT 1130 00:46:16,520 --> 00:46:18,480 IS HOW TO MEASURE. 1131 00:46:18,480 --> 00:46:22,320 CAN WE TYING NOSED PICS, WE 1132 00:46:22,320 --> 00:46:23,440 DONALD HAVE A SCREEN FOR IT 1133 00:46:23,440 --> 00:46:25,520 BUT WE HAVE CLINICALLY 1134 00:46:25,520 --> 00:46:26,280 AVAILABLE TOOLS AND RESEARCH 1135 00:46:26,280 --> 00:46:27,920 TOOLS IN THE VARIOUS DOMAINS 1136 00:46:27,920 --> 00:46:31,080 AND THIS IS FROM A CONSENSUS 1137 00:46:31,080 --> 00:46:32,560 CONFERENCE UNDER THE SOCIETY 1138 00:46:32,560 --> 00:46:35,000 OF CRITICAL CARE MEDICINE THAT 1139 00:46:35,000 --> 00:46:36,280 WAS PUBLISHED IN 2020 LOOKING 1140 00:46:36,280 --> 00:46:39,240 AT WHAT SOURCE OF TOOLS ARE 1141 00:46:39,240 --> 00:46:40,400 BEING USED AND PEOPLE THINK 1142 00:46:40,400 --> 00:46:42,680 ARE A GOOD IDEA, EXPERTS DOING 1143 00:46:42,680 --> 00:46:44,640 THE WORK IN THE FIELD AND 1144 00:46:44,640 --> 00:46:46,720 THERE IS STRONG CONSENSUS 1145 00:46:46,720 --> 00:46:49,960 AROUND THE USE FORTH O C A FOR 1146 00:46:49,960 --> 00:46:51,280 COGNITION, THE HOSPITAL 1147 00:46:51,280 --> 00:46:53,160 SANCTION SITE AND DEPRESSION 1148 00:46:53,160 --> 00:46:54,440 SCALE FOR ANXIETY AND 1149 00:46:54,440 --> 00:46:56,480 DEPRESSION BUT WHEN IT COMES 1150 00:46:56,480 --> 00:47:01,680 TO SCREENING FOR POSTTRAUMATIC 1151 00:47:01,680 --> 00:47:04,320 DISTRESS OR ANXIETY, THERE IS 1152 00:47:04,320 --> 00:47:06,560 REALLY NO GOLD STANDARD. 1153 00:47:06,560 --> 00:47:07,400 NEXT SLIDE. 1154 00:47:07,400 --> 00:47:08,920 UNFORTUNATELY IF YOU DON'T 1155 00:47:08,920 --> 00:47:10,080 MEASURE, YOU WON'T FIND AND 1156 00:47:10,080 --> 00:47:16,600 MANY OF US CAME TO THIS FIELD 1157 00:47:16,600 --> 00:47:17,640 THROUGH CRITICAL MEDICAL 1158 00:47:17,640 --> 00:47:19,400 TRAINING WHICH IS VERY LIGHT 1159 00:47:19,400 --> 00:47:21,600 ON COGNITIVE AND MENTAL HEALTH 1160 00:47:21,600 --> 00:47:24,120 DOMAINS BUT WE HAVE HAD SOME 1161 00:47:24,120 --> 00:47:25,360 REALLY SHOCKING CASES WHERE 1162 00:47:25,360 --> 00:47:30,080 PEOPLE COME INTO CLINICS, LOOK 1163 00:47:30,080 --> 00:47:31,920 TOTALLY FINE. 1164 00:47:31,920 --> 00:47:33,440 MAYBE THEY HAVEN'T BEEN BACK 1165 00:47:33,440 --> 00:47:35,400 TO WORK AND IF YOU LOOK AT 1166 00:47:35,400 --> 00:47:37,760 THEM FROM THE OUTSIDE, THEY 1167 00:47:37,760 --> 00:47:39,520 LOOK OKAY AND THIS IS A 1168 00:47:39,520 --> 00:47:40,760 BARRIER TO THEM BEST OF THING 1169 00:47:40,760 --> 00:47:41,960 THE HELP THEY NEED. 1170 00:47:41,960 --> 00:47:44,480 HOWEVER IF YOU ASK SPECIFIC 1171 00:47:44,480 --> 00:47:46,160 QUESTIONS, YOU FIND A LOT OF 1172 00:47:46,160 --> 00:47:46,760 NEED. 1173 00:47:46,760 --> 00:47:49,000 FOR EXAMPLE, OUR LADY IN THIS 1174 00:47:49,000 --> 00:47:50,760 CASE WANTED TO RETURN TO WORK 1175 00:47:50,760 --> 00:47:54,080 BUT COULDN'T GET UP FROM AN 1176 00:47:54,080 --> 00:47:55,040 EXAM TABLE WITHOUT ASSISTANCE 1177 00:47:55,040 --> 00:47:57,680 AND WAS ONE OF THOSE WHO COULD 1178 00:47:57,680 --> 00:47:59,760 NOT DO THE SIX-MINUTE WALK. 1179 00:47:59,760 --> 00:48:05,680 I SAW A IT SPECIALIST IN HIS 1180 00:48:05,680 --> 00:48:07,400 40s, FOUR MONTHS OUT OF 1181 00:48:07,400 --> 00:48:10,560 HOSPITALIZATION AND TWO MONTHS 1182 00:48:10,560 --> 00:48:16,320 ON E CMO, HIS PFTS ARE ALMOST 1183 00:48:16,320 --> 00:48:18,160 NORMAL, HE CAN WALK AND EVEN 1184 00:48:18,160 --> 00:48:20,320 QUALITY A LITTLE BUT CAN'T GO 1185 00:48:20,320 --> 00:48:22,520 BACK WOULD WORK BECAUSE HIS 1186 00:48:22,520 --> 00:48:25,320 COGNITIVE DEFICITS ARE SO 1187 00:48:25,320 --> 00:48:25,800 SEVERE. 1188 00:48:25,800 --> 00:48:28,400 AND THEN A COLLEAGUE IN HIS 1189 00:48:28,400 --> 00:48:30,440 60s, WENT BACK TO WORK 1190 00:48:30,440 --> 00:48:31,920 PART-TIME, I HAD A LOVELY 1191 00:48:31,920 --> 00:48:33,640 CONVERSATION WITH HIM AND HIS 1192 00:48:33,640 --> 00:48:35,080 WIFE AND THOUGHT HE WAS DOING 1193 00:48:35,080 --> 00:48:37,520 QUITE WELL AND WILL THEN JIM 1194 00:48:37,520 --> 00:48:41,200 WENT IN TO DO THE MENTAL 1195 00:48:41,200 --> 00:48:42,600 STATUS EXAM AND HE WAS UNABLE 1196 00:48:42,600 --> 00:48:48,520 NO NAME THE YEAR OR THE 1197 00:48:48,520 --> 00:48:49,520 PRESIDENT. 1198 00:48:49,520 --> 00:48:50,560 NEXT SLIDE, PLEASE. 1199 00:48:50,560 --> 00:48:52,600 SO OUR CURRENT STATUS THAT WE 1200 00:48:52,600 --> 00:48:55,760 ARE VERY FOCUSED ON IN IC 1201 00:48:55,760 --> 00:48:56,840 WHICH WE NEED TO BE. 1202 00:48:56,840 --> 00:48:59,040 IF YOU DON'T SURVIVE YOUR 1203 00:48:59,040 --> 00:49:00,440 CHRIS CALL ILLNESS, YOU ARE 1204 00:49:00,440 --> 00:49:01,480 CAN'T GO TO ANY SURVIVOR 1205 00:49:01,480 --> 00:49:04,120 PROGRAM BUT WHEN A PATIENT 1206 00:49:04,120 --> 00:49:06,560 LEAVES ICU FROM A RESEARCH AND 1207 00:49:06,560 --> 00:49:07,840 CLINICAL STANDPOINT, THINGS 1208 00:49:07,840 --> 00:49:10,040 START TO GET FUZZY AND FALL 1209 00:49:10,040 --> 00:49:13,240 APART AND ANYONE WHO HAS READ 1210 00:49:13,240 --> 00:49:14,960 A DISCHARGE SUMMARY OF SOMEONE 1211 00:49:14,960 --> 00:49:17,760 THEY TOOK CARE OF IN IC HAD 1212 00:49:17,760 --> 00:49:21,960 YOU IS A LITTLE LIKE THE 1213 00:49:21,960 --> 00:49:25,960 TELEPHONES, A LOT OF DATA GETS 1214 00:49:25,960 --> 00:49:27,920 LOST AND THEY ARE TOLD YOUR 1215 00:49:27,920 --> 00:49:29,640 CARE ENDS THE DAY YOU ARE 1216 00:49:29,640 --> 00:49:31,240 DISCHARGED AND PATIENTS SEE IN 1217 00:49:31,240 --> 00:49:34,320 AS A BIG BLACK HOLE AND LEFT 1218 00:49:34,320 --> 00:49:36,440 WITH NO IDEA HOW TO ADDRESS 1219 00:49:36,440 --> 00:49:37,200 THE PROBLEMS. 1220 00:49:37,200 --> 00:49:41,280 THIS IS FROM AN ARTIST WHO IS 1221 00:49:41,280 --> 00:49:43,360 A FANTASTIC ARTIST WHO DID A 1222 00:49:43,360 --> 00:49:45,240 SERIES OF DRAWINGS ABOUT HER 1223 00:49:45,240 --> 00:49:47,160 OWN EXPERIENCE IN ICU AND WE 1224 00:49:47,160 --> 00:49:49,280 ALSO HAVE A HOLE IN DATA 1225 00:49:49,280 --> 00:49:52,160 BECAUSE IT IS VERY HARD TO 1226 00:49:52,160 --> 00:49:54,000 TRACK PATIENTS DOWN ONCE THEY 1227 00:49:54,000 --> 00:49:55,360 LEAVE THE HOSPITAL. 1228 00:49:55,360 --> 00:49:56,280 NEXT SLIDE, PLEASE. 1229 00:49:56,280 --> 00:49:57,680 OUR PATIENTS TOLD US THEY 1230 00:49:57,680 --> 00:50:01,960 DIDN'T EVEN KNOW WHAT TO 1231 00:50:01,960 --> 00:50:06,120 GOOGLE. 1232 00:50:06,120 --> 00:50:07,640 Dr. HARRELL LISTED THESE AND 1233 00:50:07,640 --> 00:50:08,440 SAID THIS BETTER. 1234 00:50:08,440 --> 00:50:10,760 THERE WAS NO SUPPORT GIVEN OR 1235 00:50:10,760 --> 00:50:18,440 OFFERED TO US, NO INFORMATION, 1236 00:50:18,440 --> 00:50:21,080 AND KNOWING YOUR CRITICAL CARE 1237 00:50:21,080 --> 00:50:21,880 Dr. AND TALKING ABOUT WHAT 1238 00:50:21,880 --> 00:50:24,840 IS NEXT IN THE PROCESS SHOULD 1239 00:50:24,840 --> 00:50:26,560 BE A MANDATORY PROCESS. 1240 00:50:26,560 --> 00:50:28,560 NOT EVERY PATIENT HAS THE SAME 1241 00:50:28,560 --> 00:50:29,080 CHANCE TO RECOVER. 1242 00:50:29,080 --> 00:50:32,400 THIS IS A VERY SIMILAR PATIENT 1243 00:50:32,400 --> 00:50:34,000 TO Dr. HARRELL WHO DID NOT 1244 00:50:34,000 --> 00:50:35,760 THINK SHE WOULD BE ABLE TO 1245 00:50:35,760 --> 00:50:37,920 WALK AGAIN BUT HAD GREAT 1246 00:50:37,920 --> 00:50:39,360 INSURANCE, A FAMILY, GREAT 1247 00:50:39,360 --> 00:50:42,600 COMMUNITY, A CHURCH, WENT FROM 1248 00:50:42,600 --> 00:50:44,760 LPAC IN-PATIENT REHAB TO 1249 00:50:44,760 --> 00:50:46,800 OUT-PATIENT REHAB AND WHEN SHE 1250 00:50:46,800 --> 00:50:50,320 GOT OUT OF OUT-PATIENT REHAB, 1251 00:50:50,320 --> 00:50:52,360 HIRED A TRAINER AND WENT TO 1252 00:50:52,360 --> 00:50:53,640 THE GYM FOR 180-STRAIGHT DAYS 1253 00:50:53,640 --> 00:50:55,960 AND THAT IS HOW SHE HAD AN 1254 00:50:55,960 --> 00:50:57,160 ADEQUATE RECOVERY. 1255 00:50:57,160 --> 00:51:04,000 SHE DID HER OWN COGNITIVE 1256 00:51:04,000 --> 00:51:05,520 REHAB BY MAKING COMPLEX REESE 1257 00:51:05,520 --> 00:51:07,120 PIECE AND FELT SHE WAS 1258 00:51:07,120 --> 00:51:08,200 PROVIDING SOMETHING TO THE 1259 00:51:08,200 --> 00:51:09,520 COMMUNITY WHEN THE RECIPES 1260 00:51:09,520 --> 00:51:11,280 WORKED OUT AND WAS ABLE TO 1261 00:51:11,280 --> 00:51:13,040 HAVE SUCH A GREAT RECOVERY SHE 1262 00:51:13,040 --> 00:51:15,640 WAS ONE OF OUR PATIENT 1263 00:51:15,640 --> 00:51:16,960 SPEAKERS SEVERAL YEARS AGO AND 1264 00:51:16,960 --> 00:51:20,400 HER NAME IS MILLIE AND IS HERE 1265 00:51:20,400 --> 00:51:22,280 WITH HER HUSBAND WOODY. 1266 00:51:22,280 --> 00:51:23,080 NEXT SLIDE. 1267 00:51:23,080 --> 00:51:24,480 IN CONTRAST, I HAD A PATIENT 1268 00:51:24,480 --> 00:51:30,080 IN HER 30s WHEN A 1269 00:51:30,080 --> 00:51:31,200 CATASTROPHIC PERIPARTUM 1270 00:51:31,200 --> 00:51:34,280 CRITICAL ILLNESS. 1271 00:51:34,280 --> 00:51:36,600 SHE HAD GOOD INSURANCE BUT NO 1272 00:51:36,600 --> 00:51:38,680 PCP TO SIGN PT PAPERWORK. 1273 00:51:38,680 --> 00:51:42,320 SHE HAD A SUPPORTIVE HUSBAND 1274 00:51:42,320 --> 00:51:44,440 WHO HAD TO BE DEPLOYED AGAIN 1275 00:51:44,440 --> 00:51:47,880 AND HAD A 6-YEAR-OLD AND 1276 00:51:47,880 --> 00:51:52,000 NEWBORN AT HOME AND WHEN HER 1277 00:51:52,000 --> 00:51:53,840 HUSBAND DEPLOYED AGAIN, I 1278 00:51:53,840 --> 00:51:55,680 ASKED HER HOW SHE WOULD TAKE 1279 00:51:55,680 --> 00:51:57,640 CARE OF THE NEWBORN AND SHE 1280 00:51:57,640 --> 00:51:59,760 TOLD ME SHE WOULD LIE DOWN AND 1281 00:51:59,760 --> 00:52:02,320 TAKE CARE OF THE BABY LYING 1282 00:52:02,320 --> 00:52:02,760 DOWN. 1283 00:52:02,760 --> 00:52:04,600 ANOTHER PATIENT IN HIS 40s, 1284 00:52:04,600 --> 00:52:05,880 NO INSURANCE, CAN'T WORK DUE 1285 00:52:05,880 --> 00:52:07,760 TO HIS ILLNESS AND HE WENT 1286 00:52:07,760 --> 00:52:12,760 HOME WITH A TRACH WHICH HE 1287 00:52:12,760 --> 00:52:14,360 BASICALLY IS HAVING THE 1288 00:52:14,360 --> 00:52:16,360 SUPPLIES AND OXYGEN DONATED. 1289 00:52:16,360 --> 00:52:20,840 HE IS DUE IN COURT FOR CHILD 1290 00:52:20,840 --> 00:52:24,120 SUPPORT AND NEEDING HELP WITH 1291 00:52:24,120 --> 00:52:26,640 HOW TO NAVIGATE THE LEGAL 1292 00:52:26,640 --> 00:52:28,560 SYSTEM AFRAID OF EXPOSURES SO 1293 00:52:28,560 --> 00:52:34,200 THESE PATIENTS IN CONTRAST ARE 1294 00:52:34,200 --> 00:52:37,160 NOT DOING SO WELL DESPITE THE 1295 00:52:37,160 --> 00:52:43,160 SAME CARE IN THE ICU. 1296 00:52:43,160 --> 00:52:45,800 SO I PUT TOGETHER THIS SLIDE 1297 00:52:45,800 --> 00:52:46,840 WITH THE INTERVENTIONS AT THE 1298 00:52:46,840 --> 00:52:49,240 BOTTOM OF THE SLIDE BUT WE 1299 00:52:49,240 --> 00:52:50,880 KNOW VERY LITTLE, KEEP 1300 00:52:50,880 --> 00:52:51,840 CLICKING, PLEASE, ABOUT EACH 1301 00:52:51,840 --> 00:52:52,520 OF THESE. 1302 00:52:52,520 --> 00:52:55,120 AND WE SEE THERE IS A TRAM 1303 00:52:55,120 --> 00:53:05,640 JECT TREE -- TRAJECTORY OF 1304 00:53:05,640 --> 00:53:06,000 RECOVERY. 1305 00:53:06,000 --> 00:53:07,320 NEXT SLIDE. 1306 00:53:07,320 --> 00:53:09,880 THE MAJOR GAPS WITH NO 1307 00:53:09,880 --> 00:53:13,080 UNIFYING DIAGNOSIS CODES, NO 1308 00:53:13,080 --> 00:53:15,160 CONSENSUS ON MEASUREMENT, NO 1309 00:53:15,160 --> 00:53:17,680 CARE PATHWAYS, NO INSURANCE 1310 00:53:17,680 --> 00:53:20,400 COVERAGE, DIFFICULT TO REACH 1311 00:53:20,400 --> 00:53:22,360 RESEARCH POPULATION, NO 1312 00:53:22,360 --> 00:53:24,760 FUNDING HOME SPECIFIC TO THIS 1313 00:53:24,760 --> 00:53:28,160 AREA AND LITTLE INTEGRATION 1314 00:53:28,160 --> 00:53:28,640 INTO TRAINING. 1315 00:53:28,640 --> 00:53:36,840 I AM SURPRISED THERE ARE A 1316 00:53:36,840 --> 00:53:38,440 VERY FEW CLINICAL PROGRAMS 1317 00:53:38,440 --> 00:53:40,040 FOLLOWING PATIENTS AFTER 1318 00:53:40,040 --> 00:53:43,280 DISCHARGE AND IN RURAL AREAS, 1319 00:53:43,280 --> 00:53:43,840 EVEN FEWER. 1320 00:53:43,840 --> 00:53:45,880 THERE IS LITTLE AWARENESS OF 1321 00:53:45,880 --> 00:53:48,960 WHAT IS KNOWN OR NEEDED AND 1322 00:53:48,960 --> 00:53:51,680 RESEARCH IN THIS AREA IS UNDER 1323 00:53:51,680 --> 00:53:53,320 DEVELOPED IN THESE AREAS. 1324 00:53:53,320 --> 00:53:54,240 NEXT SLIDE, PLEASE. 1325 00:53:54,240 --> 00:53:55,640 WE NEED THIS INFRASTRUCTURE, 1326 00:53:55,640 --> 00:53:58,040 HOWEVER, NOT ONLY TO PROVIDE 1327 00:53:58,040 --> 00:53:59,800 FOR CRITICAL AND CLINICAL CARE 1328 00:53:59,800 --> 00:54:01,200 BUT TO LEARN ABOUT THE 1329 00:54:01,200 --> 00:54:06,080 OUTCOMES OF THESE ILLNESSES TO 1330 00:54:06,080 --> 00:54:14,720 IMPROVE OUR IN-I CU CARE AND 1331 00:54:14,720 --> 00:54:16,880 THERE HAVE BEEN IN THE PLACES 1332 00:54:16,880 --> 00:54:19,680 THAT HAD HISTORY TO LEARN 1333 00:54:19,680 --> 00:54:20,160 ABOUT THE DISEASE. 1334 00:54:20,160 --> 00:54:25,000 SO I WAS ASKED TO COME UP WITH 1335 00:54:25,000 --> 00:54:26,400 A HIGH RISK-HIGH REWARD 1336 00:54:26,400 --> 00:54:28,080 CONCEPT FOR HOW TO PUSH THIS 1337 00:54:28,080 --> 00:54:28,400 FORWARD. 1338 00:54:28,400 --> 00:54:31,440 I DON'T HAVE ANY HIGH-RISK BUT 1339 00:54:31,440 --> 00:54:36,200 WE DO HAVE THE REWARD FOR 1340 00:54:36,200 --> 00:54:38,440 SUPPORT FOR SHARED DATA 1341 00:54:38,440 --> 00:54:40,720 INFRASTRUCTURE AND IMPROVE 1342 00:54:40,720 --> 00:54:41,360 SURVIVORSHIP FOR PATIENTS. 1343 00:54:41,360 --> 00:54:44,640 THERE IS A WEALTH OF DATA. 1344 00:54:44,640 --> 00:54:46,040 CAIRO, FOR EXAMPLE, WE MEET 1345 00:54:46,040 --> 00:54:47,200 EVERY MONTH AND SHARE 1346 00:54:47,200 --> 00:54:48,680 KNOWLEDGE AND PEER SUPPORT FOR 1347 00:54:48,680 --> 00:54:50,720 EACH OTHER. 1348 00:54:50,720 --> 00:54:53,440 WE CAN USE THOSE CLINICAL 1349 00:54:53,440 --> 00:54:58,000 SITES AS A LIVING LABORATORY 1350 00:54:58,000 --> 00:54:59,640 TO BOTH TEST INTERVENTION AND 1351 00:54:59,640 --> 00:55:01,560 ASK THE RIGHT QUESTIONS AND 1352 00:55:01,560 --> 00:55:04,040 THEN ALSO WHEN WE HAVE NEW 1353 00:55:04,040 --> 00:55:06,800 DATA TO DEPLOY THE NEW 1354 00:55:06,800 --> 00:55:15,120 KNOWLEDGE INTO CLINICAL CARE 1355 00:55:15,120 --> 00:55:18,200 AND Dr. SEMLER WILL TALK IN 1356 00:55:18,200 --> 00:55:23,120 SECTION FOUR ABOUT THIS WHICH 1357 00:55:23,120 --> 00:55:24,200 IS UNIQUELILY STUDYING THIS 1358 00:55:24,200 --> 00:55:24,960 POPULATION. 1359 00:55:24,960 --> 00:55:26,600 IT IS A COMPLEX PROBLEM BUT 1360 00:55:26,600 --> 00:55:29,440 SEEING THE PATIENTS IN A 1361 00:55:29,440 --> 00:55:30,960 CLINICAL SETTING IS THE FOCUS 1362 00:55:30,960 --> 00:55:32,480 IN VERY FEW CENTERS AND I WILL 1363 00:55:32,480 --> 00:55:33,480 END THERE. 1364 00:55:33,480 --> 00:55:34,800 THANK YOU FOR YOUR ATTENTION 1365 00:55:34,800 --> 00:55:42,880 AND LOOK FORWARD TO THE REST 1366 00:55:42,880 --> 00:55:43,720 OF THE SECTION. 1367 00:55:43,720 --> 00:55:46,720 >>THANKS SO MUCH CARLA FOR A 1368 00:55:46,720 --> 00:55:47,640 FANTASTIC TALK. 1369 00:55:47,640 --> 00:55:50,240 WE WANTED TO USE THIS TALK TO 1370 00:55:50,240 --> 00:55:56,880 SET THE STAGE FOR WORKING WITH 1371 00:55:56,880 --> 00:55:58,520 THE CLINICAL SYNDROME AND YOU 1372 00:55:58,520 --> 00:55:59,560 DID THAT NICELY FOR US. 1373 00:55:59,560 --> 00:56:01,760 I WILL REACH OUT TO MY 1374 00:56:01,760 --> 00:56:02,760 COMODERATOR AND DO WE HAVE ANY 1375 00:56:02,760 --> 00:56:04,960 QUESTIONS IN THE CHART? 1376 00:56:04,960 --> 00:56:06,440 >>WE'RE STARTING TO GET A 1377 00:56:06,440 --> 00:56:07,680 LITTLE BIT. 1378 00:56:07,680 --> 00:56:10,200 I WANT TO ENCOURAGE PEOPLE TO 1379 00:56:10,200 --> 00:56:14,040 USE THE CHAT FOR AN ADDITIONAL 1380 00:56:14,040 --> 00:56:17,680 CHANNEL IN THINKING ABOUT THE 1381 00:56:17,680 --> 00:56:20,440 ITEMS AVAILABLE TO THE REPORT. 1382 00:56:20,440 --> 00:56:22,520 I WILL START WITH THIS ONE, 1383 00:56:22,520 --> 00:56:25,920 WHY IS THIS YOUR PROBLEM? 1384 00:56:25,920 --> 00:56:27,880 SHOULDN'T PRIMARY CARE RESOLVE 1385 00:56:27,880 --> 00:56:28,160 THIS? 1386 00:56:28,160 --> 00:56:30,200 CAN YOU TALK ABOUT PRIMARY 1387 00:56:30,200 --> 00:56:30,680 CARE? 1388 00:56:30,680 --> 00:56:32,280 >>YES, THANK YOU FOR ASKING. 1389 00:56:32,280 --> 00:56:34,120 THIS HAS ACTUALLY BEEN LOOKED 1390 00:56:34,120 --> 00:56:36,440 AT, FOR EXAMPLE, IN EUROPE, 1391 00:56:36,440 --> 00:56:40,600 THAT HAS A MORE ROBUST MIAMI 1392 00:56:40,600 --> 00:56:42,760 MAYOR CARE INFRASTRUCTURE TO 1393 00:56:42,760 --> 00:56:44,560 WORK ON SURVIVORSHIP 1394 00:56:44,560 --> 00:56:48,080 PARTICULARLY AFTER SENSE SIS 1395 00:56:48,080 --> 00:56:50,600 BY COORDINATING PRIMARY CARE 1396 00:56:50,600 --> 00:56:53,760 PHYSICIANS AND HAS SOME 1397 00:56:53,760 --> 00:56:55,000 PRIMARY CARE PHYSICIANS TO 1398 00:56:55,000 --> 00:56:56,120 HELP WITH THE OUTCOMES OF 1399 00:56:56,120 --> 00:56:57,200 QUALITY OF LIFE. 1400 00:56:57,200 --> 00:56:59,320 IN THE U.S., AND THROUGHOUT 1401 00:56:59,320 --> 00:57:01,160 OTHER COUNTRIES, WE DO NOT 1402 00:57:01,160 --> 00:57:06,560 HAVE A VERY ROBUST PRIMARY 1403 00:57:06,560 --> 00:57:08,400 FIGURES INFRASTRUCTURE. 1404 00:57:08,400 --> 00:57:09,440 TYPICALLY IN THE U.S. MANY 1405 00:57:09,440 --> 00:57:16,240 PEOPLE DON'T HAVE A PRIMARY 1406 00:57:16,240 --> 00:57:19,440 PHYSICIAN AND IF THEY DO WE DO 1407 00:57:19,440 --> 00:57:22,440 NOT GIVE THEM ANY MONEY, 1408 00:57:22,440 --> 00:57:23,200 RESEARCH, TIME. 1409 00:57:23,200 --> 00:57:26,280 AND I AM OFTEN ASKED ABOUT 1410 00:57:26,280 --> 00:57:29,680 WHAT IS NECESSARY FOR A 1411 00:57:29,680 --> 00:57:30,960 POST-ICU CLINIC AND IT IS TO 1412 00:57:30,960 --> 00:57:35,720 HAVE ONE PERSON WHO CARES 1413 00:57:35,720 --> 00:57:36,640 ABOUT THIS PROBLEM. 1414 00:57:36,640 --> 00:57:38,760 ICU IS A CLINICAL 1415 00:57:38,760 --> 00:57:40,000 SUBSPECIALTY, WE WALK INTO A 1416 00:57:40,000 --> 00:57:41,400 ROOM AND GO WE NEED TO TIE 1417 00:57:41,400 --> 00:57:43,600 THAT UP AND THOSE THINGS ARE 1418 00:57:43,600 --> 00:57:45,800 INVISIBLE TO SOMEONE WHO IS 1419 00:57:45,800 --> 00:57:47,800 NOT ROUTINELY IN THE ICU. 1420 00:57:47,800 --> 00:57:50,280 AND EVEN IN A PRIMARY CARE 1421 00:57:50,280 --> 00:57:52,640 CLINIC, THEY MAY ONLY SEE A 1422 00:57:52,640 --> 00:57:54,440 HANDFUL OF SURVIVORS OVER THE 1423 00:57:54,440 --> 00:57:57,680 YEAR SO BUILDING UP THAT 1424 00:57:57,680 --> 00:58:00,320 CLINICAL RECOGNITION AND 1425 00:58:00,320 --> 00:58:01,600 EXPERTISE AND KNOWLEDGE, I 1426 00:58:01,600 --> 00:58:06,520 REALLY SPEND MOST OF TIME TIME 1427 00:58:06,520 --> 00:58:07,360 RESEARCHING ABOUT POST-ICU 1428 00:58:07,360 --> 00:58:09,960 PROBLEMS SO I FEEL WELL 1429 00:58:09,960 --> 00:58:12,600 QUALIFIED TO ADVICE PATIENTS 1430 00:58:12,600 --> 00:58:15,480 AND FAMILIES ABOUT POST-ICU 1431 00:58:15,480 --> 00:58:16,480 TREATMENT, ET CETERA. 1432 00:58:16,480 --> 00:58:20,640 BUT EVEN IF MY OWN POST-ICU 1433 00:58:20,640 --> 00:58:21,760 CARE SPECIALTY, I HAD A 1434 00:58:21,760 --> 00:58:24,040 PROBLEM WITH ONE OF MY 1435 00:58:24,040 --> 00:58:25,480 COLLEAGUES IN PULMONARY 1436 00:58:25,480 --> 00:58:28,200 MEDICINE, WE SAW HER AFTER HER 1437 00:58:28,200 --> 00:58:29,440 CRITICAL ILLNESS AND SHE SAID 1438 00:58:29,440 --> 00:58:31,680 I DON'T KNOW WHO TO ASK ABOUT 1439 00:58:31,680 --> 00:58:33,520 THIS BUT LIKE MY HAIR IS 1440 00:58:33,520 --> 00:58:35,960 FALLING OUT SINCE I WAS IN THE 1441 00:58:35,960 --> 00:58:38,560 ICU AND I WAS LIKE YES AND MY 1442 00:58:38,560 --> 00:58:39,200 COLLEAGUE WAS LIKE I DON'T 1443 00:58:39,200 --> 00:58:40,520 KNOW AND I AM LIKE YES, THIS 1444 00:58:40,520 --> 00:58:42,520 IS ONE OF THE THINGS WE KNOW, 1445 00:58:42,520 --> 00:58:47,720 LET'S TELL HER ABOUT IT AND 1446 00:58:47,720 --> 00:58:48,360 ADVICE VIES HER. 1447 00:58:48,360 --> 00:58:51,160 AND I WAS ABLE TO UNIQUELY DO 1448 00:58:51,160 --> 00:58:51,440 THAT. 1449 00:58:51,440 --> 00:58:56,480 I WAS ABLE TO GET HER THE 1450 00:58:56,480 --> 00:58:58,440 GERMAN STUDY FROM THE GROUP 1451 00:58:58,440 --> 00:59:00,280 YEARS AGO AND THESE ARE ALL 1452 00:59:00,280 --> 00:59:02,600 PRIMARY CARE FOLKS AND I ASKED 1453 00:59:02,600 --> 00:59:07,680 THE RESEARCHER DID YOU CONTROL 1454 00:59:07,680 --> 00:59:09,440 FOR HOW MUCH PRESSOR SOMEBODY 1455 00:59:09,440 --> 00:59:13,320 IS ON AND WE ALL KNOW A 1456 00:59:13,320 --> 00:59:15,240 TRICKLE IS DIFFERENT FOR TWO 1457 00:59:15,240 --> 00:59:16,840 DIFFERENT PATIENTS AND THEY 1458 00:59:16,840 --> 00:59:20,480 ALL JUST LOOKED AT ME AND LIKE 1459 00:59:20,480 --> 00:59:21,880 WHY DOES MA MATTER SO THAT IS 1460 00:59:21,880 --> 00:59:23,320 WHY WE ALL NEED TO BE IN THE 1461 00:59:23,320 --> 00:59:24,800 ROOM AND ASKING THE RIGHT 1462 00:59:24,800 --> 00:59:26,400 QUESTIONS AND BE AVAILABLE TO 1463 00:59:26,400 --> 00:59:28,680 PATIENTS TO ANSWER THOSE 1464 00:59:28,680 --> 00:59:29,040 QUESTIONS. 1465 00:59:29,040 --> 00:59:29,800 >>AWESOME, CARLA. 1466 00:59:29,800 --> 00:59:32,640 WE'RE STARTING TO GET SOME 1467 00:59:32,640 --> 00:59:35,160 QUESTIONS THAT WILL LIKELY 1468 00:59:35,160 --> 00:59:36,560 START A FULL DISCUSSION. 1469 00:59:36,560 --> 00:59:38,200 FOR THOSE WHO DON'T KNOW ME, I 1470 00:59:38,200 --> 00:59:42,600 AM A HUGE FAN OF PRIMARY CARE 1471 00:59:42,600 --> 00:59:45,520 AND WHAT WAS FANTASTIC IN AN 1472 00:59:45,520 --> 00:59:49,560 OPEN FORUM WILL NOT APPEAR ON 1473 00:59:49,560 --> 00:59:52,240 THE RECORD WHILE LAUREN WAS 1474 00:59:52,240 --> 00:59:58,440 SPEAKING SO IT IS LOVELY TO 1475 00:59:58,440 --> 01:00:08,240 WELCOME CARLA SEVIN AND 1476 01:00:08,240 --> 01:00:09,360 INTRODUES JAMES JACKSON. 1477 01:00:09,360 --> 01:00:11,000 JIM IS TOO NOISE TO MENTION 1478 01:00:11,000 --> 01:00:13,840 THIS SO I WILL MENTION HE HAS 1479 01:00:13,840 --> 01:00:15,760 A PATIENT ORIENTED BOOK ON 1480 01:00:15,760 --> 01:00:16,960 RECOVERY FROM LONG COVID OUT 1481 01:00:16,960 --> 01:00:19,360 NOW OR WITHIN A MONTH OR TWO, 1482 01:00:19,360 --> 01:00:20,440 ABOUT A WEEK OR TWO. 1483 01:00:20,440 --> 01:00:23,840 I AM STILL WAITING FOR MY 1484 01:00:23,840 --> 01:00:25,800 COPY, I HAVE ALREADY 1485 01:00:25,800 --> 01:00:27,080 PREORDERED AND THIS IS NOT 1486 01:00:27,080 --> 01:00:29,560 OFFICIAL OF COURSE BUT JIM 1487 01:00:29,560 --> 01:00:32,720 JACKSON, THE FLOOR IS YOURS. 1488 01:00:32,720 --> 01:00:34,040 >>YEAH, THANK YOU, JACK. 1489 01:00:34,040 --> 01:00:36,360 GOOD TO BE HERE WITH ALL OF 1490 01:00:36,360 --> 01:00:39,960 YOU. 1491 01:00:39,960 --> 01:00:40,520 NEXT SLIDE, PLEASE. 1492 01:00:40,520 --> 01:00:47,760 I AM GLAD TO TALK ABOUT THE 1493 01:00:47,760 --> 01:00:48,240 MOVIE. 1494 01:00:48,240 --> 01:00:50,280 FIRST REALLY WANTED TO THANK 1495 01:00:50,280 --> 01:00:52,720 KIRSTEN AND I NOTICE THAT 1496 01:00:52,720 --> 01:00:55,440 QUITE A FEW PEOPLE FROM OUR 1497 01:00:55,440 --> 01:00:57,200 ICU GROUP ARE HERE TODAY, 1498 01:00:57,200 --> 01:00:58,880 LOVELY TO SEE YOU AS WELL AND 1499 01:00:58,880 --> 01:01:00,480 REALLY GREAT TO BE HERE. 1500 01:01:00,480 --> 01:01:02,000 I DON'T USUALLY WEAR A TIE. 1501 01:01:02,000 --> 01:01:03,720 I WORE A TIE TODAY AND THERE 1502 01:01:03,720 --> 01:01:05,480 IS A LITTLE BIT OF A BACK 1503 01:01:05,480 --> 01:01:06,400 STORY. 1504 01:01:06,400 --> 01:01:08,000 I WAS AT GOOD WILL WHERE I 1505 01:01:08,000 --> 01:01:10,800 LOVE TO SHOP AND THERE WAS A 1506 01:01:10,800 --> 01:01:12,640 THANKSGIVING TIE WITH TURKEYS. 1507 01:01:12,640 --> 01:01:15,600 PROBABLY HARD TO SEE BUT THESE 1508 01:01:15,600 --> 01:01:16,960 ARE THANKSGIVING TURKEYS AND I 1509 01:01:16,960 --> 01:01:20,840 GOT THE TIE OUT THIS MORNING 1510 01:01:20,840 --> 01:01:23,560 AND I THOUGHT GOSH, I CAN'T 1511 01:01:23,560 --> 01:01:26,400 WEAR A THANKSGIVING TURKEY TIE 1512 01:01:26,400 --> 01:01:28,360 ALTHOUGH IT IS RED, CONTRASTS 1513 01:01:28,360 --> 01:01:30,920 WITH BLUE AND ALL THAT KIND OF 1514 01:01:30,920 --> 01:01:32,840 THING AND THEN I THOUGHT I AM 1515 01:01:32,840 --> 01:01:33,760 GOING TO WEAR THIS 1516 01:01:33,760 --> 01:01:35,960 THANKSGIVING TIE BECAUSE IT 1517 01:01:35,960 --> 01:01:37,440 REMINDS ME OF GRATITUDE AND AT 1518 01:01:37,440 --> 01:01:39,600 THE RISK OF SOUNDING A LITTLE 1519 01:01:39,600 --> 01:01:41,640 CHEESEY, IF YOU WILL, I HAVE A 1520 01:01:41,640 --> 01:01:42,600 LOT OF GRATITUDE FOR BEING 1521 01:01:42,600 --> 01:01:45,240 HERE AND THE WORK WE ARE ALL 1522 01:01:45,240 --> 01:01:46,640 DOING TOGETHER, THE WORK TO 1523 01:01:46,640 --> 01:01:48,440 PARTICIPATE IN IT AND DO 1524 01:01:48,440 --> 01:01:51,000 MEANINGFUL WORK, IT IS REALLY 1525 01:01:51,000 --> 01:01:52,280 A GREAT BLESSING AND TO BE 1526 01:01:52,280 --> 01:02:00,360 ABLE TO WORK WITH YOU ALL ON 1527 01:02:00,360 --> 01:02:02,720 THE CALL PATIENTS REALLY 1528 01:02:02,720 --> 01:02:03,360 ANIMATES ME. 1529 01:02:03,360 --> 01:02:06,160 AND ONE OF THE THINGS WE NEED 1530 01:02:06,160 --> 01:02:09,080 TO ENGAGE HAS TO DO WITH 1531 01:02:09,080 --> 01:02:09,960 MEASURING BRAIN DYSFUNCTION IN 1532 01:02:09,960 --> 01:02:11,160 SURVIVORS OF CARDS AND THAT IS 1533 01:02:11,160 --> 01:02:13,000 WHAT WE WILL TALK ABOUT. 1534 01:02:13,000 --> 01:02:16,880 I AM A VERY BIG-PICTURE 1535 01:02:16,880 --> 01:02:17,400 THINKER. 1536 01:02:17,400 --> 01:02:19,120 WHEN TIM GIRARD AND I WERE 1537 01:02:19,120 --> 01:02:20,480 TEAMMATES, IF YOU WILL, WHEN 1538 01:02:20,480 --> 01:02:22,680 HE WAS AT VANDERBILT, WE WOULD 1539 01:02:22,680 --> 01:02:23,640 OFTEN HAVE CONVERSATIONS AND 1540 01:02:23,640 --> 01:02:25,560 HE WAS ALWAYS IN THE DETAILS 1541 01:02:25,560 --> 01:02:27,960 AND I WAS ALWAYS NOT IN THE 1542 01:02:27,960 --> 01:02:28,280 DETAILS. 1543 01:02:28,280 --> 01:02:32,280 SO YOU WILL HEAR A LOT OF 1544 01:02:32,280 --> 01:02:33,640 BROAD BRUSH THEMES HERE TODAY 1545 01:02:33,640 --> 01:02:37,040 BUT I THINK THEY ARE REALLY 1546 01:02:37,040 --> 01:02:39,040 IMPORTANT SO BUCKLE YOUR SEAT 1547 01:02:39,040 --> 01:02:39,560 BELT. 1548 01:02:39,560 --> 01:02:40,680 WE WILL GO PRETTY FAST. 1549 01:02:40,680 --> 01:02:42,880 GOT A LOT OF SLIDES TO COVER. 1550 01:02:42,880 --> 01:02:43,760 NEXT SLIDE, PLEASE. 1551 01:02:43,760 --> 01:02:48,000 I HAVE NO DISCLOSURES. 1552 01:02:48,000 --> 01:02:49,800 NEXT SLIDE, PLEASE. 1553 01:02:49,800 --> 01:02:52,000 SO THAT COGNITIVE IMPAIRMENT 1554 01:02:52,000 --> 01:02:55,640 IS A PROBLEM AFTER CRITICAL 1555 01:02:55,640 --> 01:02:56,440 ILLNESS HAS BEEN WELL 1556 01:02:56,440 --> 01:02:56,920 ESTABLISHED. 1557 01:02:56,920 --> 01:02:59,720 I HAD A FOOTBALL COACH NAMED 1558 01:02:59,720 --> 01:03:00,920 BOB KNIGHT AND IN HIGH SCHOOL, 1559 01:03:00,920 --> 01:03:03,320 WE WOULD HAVE THESE TWO A DAYS 1560 01:03:03,320 --> 01:03:05,320 AND IT WOULD BE REALLY HOT AND 1561 01:03:05,320 --> 01:03:07,280 I WOULD SAY COACH IT IS REALLY 1562 01:03:07,280 --> 01:03:08,720 HOT AND HE WOULD SCREAM AT ME 1563 01:03:08,720 --> 01:03:11,080 IN A WAY YOU COULD IN THE 1564 01:03:11,080 --> 01:03:15,120 80s BUT NOT TODAY, HE WOULD 1565 01:03:15,120 --> 01:03:18,720 SAY JACKSON DON'T STATE THE 1566 01:03:18,720 --> 01:03:21,240 OBVIOUS AND WOULD GET SO SANG 1567 01:03:21,240 --> 01:03:23,600 AGREE WITH ME AND I AM STATING 1568 01:03:23,600 --> 01:03:29,800 THE OBVIOUS HERE WHEN I SAY 1569 01:03:29,800 --> 01:03:32,680 LONG-TERM COGNITIVE IMPAIRMENT 1570 01:03:32,680 --> 01:03:34,560 IS COMMON AFTER CRITICAL 1571 01:03:34,560 --> 01:03:34,880 ILLNESS. 1572 01:03:34,880 --> 01:03:36,520 WE'RE LESS GOOD AT FIGURING 1573 01:03:36,520 --> 01:03:38,600 OUT WHAT THAT MEANS FROM A 1574 01:03:38,600 --> 01:03:39,680 FUNCTIONAL STANDPOINT, IF YOU 1575 01:03:39,680 --> 01:03:41,480 WILL, AND THAT IS WHAT WE WILL 1576 01:03:41,480 --> 01:03:43,680 SPEND A LOT OF OUR TIME ON 1577 01:03:43,680 --> 01:03:44,840 TODAY. 1578 01:03:44,840 --> 01:03:45,760 NEXT SLIDE, PLEASE. 1579 01:03:45,760 --> 01:03:48,160 SO HOW DOES ONE DEFINE 1580 01:03:48,160 --> 01:03:49,760 COGNITIVE DYSFUNCTION OR 1581 01:03:49,760 --> 01:03:51,240 COGNITIVE IMPAIRMENT? 1582 01:03:51,240 --> 01:03:53,240 WHAT TERM DO WE EVEN USE? 1583 01:03:53,240 --> 01:03:54,520 IT IS A GREAT QUESTION AND ONE 1584 01:03:54,520 --> 01:03:57,960 OF THE PROBLEMS WE SHOULD JUST 1585 01:03:57,960 --> 01:03:59,000 ACKNOWLEDGE, NO DEFENSIVENESS 1586 01:03:59,000 --> 01:04:01,640 HERE, I MEAN THERE ARE AREAS 1587 01:04:01,640 --> 01:04:03,120 IN THE NEUROPSYCHOLOGY ARENA 1588 01:04:03,120 --> 01:04:05,240 WHERE WE NEED TO DO BETTER, 1589 01:04:05,240 --> 01:04:06,040 GET BETTER. 1590 01:04:06,040 --> 01:04:09,880 SO ONE CHALLENGE WE SHOULD 1591 01:04:09,880 --> 01:04:11,760 ACKNOWLEDGE HAS TO DO WITH THE 1592 01:04:11,760 --> 01:04:16,440 PROBLEM OF COGNITIVE DISPUCKS 1593 01:04:16,440 --> 01:04:20,600 AND -- DYSFUNCTION AND THAT IS 1594 01:04:20,600 --> 01:04:24,640 DIFFERENT PEOPLE USE DIFFERENT 1595 01:04:24,640 --> 01:04:25,600 TESTS AND STRATEGIES. 1596 01:04:25,600 --> 01:04:27,040 WHAT ONE PERSON MAY CALL IT 1597 01:04:27,040 --> 01:04:29,600 MAY NOT BE IDENTIFIED AS 1598 01:04:29,600 --> 01:04:31,920 COGNITIVE IMPAIRMENT BY 1599 01:04:31,920 --> 01:04:32,560 SOMEONE ELSE. 1600 01:04:32,560 --> 01:04:35,360 BUT IN GENERAL THE WAY WE HAVE 1601 01:04:35,360 --> 01:04:37,080 USUALLY DEFINED IT IN THE 1602 01:04:37,080 --> 01:04:39,840 CONTEXT OF MOST RESEARCH IS WE 1603 01:04:39,840 --> 01:04:42,160 USE A BATTERY OF TESTS -- I 1604 01:04:42,160 --> 01:04:44,360 HAVE GOT MANY OF THEM IN MY 1605 01:04:44,360 --> 01:04:46,240 OFFICE BEHIND ME -- AND YOU 1606 01:04:46,240 --> 01:04:49,960 KNOW IF SOMEONE HAS AN 1607 01:04:49,960 --> 01:04:52,360 ABNORMAL PERFORMANCE ON THAT 1608 01:04:52,360 --> 01:04:54,160 BATTERY OF OBJECTIVES TESTS, 1609 01:04:54,160 --> 01:04:55,800 THEY ARE IMPAIRED, THE WAY WE 1610 01:04:55,800 --> 01:04:56,480 THINK ABOUT IT. 1611 01:04:56,480 --> 01:04:58,680 AND WE TEND TO THINK OF 1612 01:04:58,680 --> 01:05:01,640 IMPAIRMENT IN A VERY BINARY 1613 01:05:01,640 --> 01:05:02,920 FASHION, HE EITHER ARE OR 1614 01:05:02,920 --> 01:05:06,040 AREN'T AND THAT I THINK IS 1615 01:05:06,040 --> 01:05:07,760 PROBLEMATIC. 1616 01:05:07,760 --> 01:05:10,120 THERE ARE CLEAR STRENGTHS AND 1617 01:05:10,120 --> 01:05:11,280 MEANINGFUL LIMITATIONS IN THIS 1618 01:05:11,280 --> 01:05:12,880 APPROACH AND WE'LL TALK ABOUT 1619 01:05:12,880 --> 01:05:13,360 THOSE. 1620 01:05:13,360 --> 01:05:15,360 YEARS AGO IN MY EARLY DAYS OF 1621 01:05:15,360 --> 01:05:21,040 MY CAREER, WE DID A STUDY OF 1622 01:05:21,040 --> 01:05:22,960 ADC TRIALS, TIM GIRARD LED IT, 1623 01:05:22,960 --> 01:05:25,440 I HAD A LITTLE MAZDA HATCHBACK 1624 01:05:25,440 --> 01:05:27,160 AND DROVE IT ALL OVER ALABAMA 1625 01:05:27,160 --> 01:05:30,800 AND TENNESSEE AND OCCASIONALLY 1626 01:05:30,800 --> 01:05:31,440 MISSISSIPPI, SOMETIMES 1627 01:05:31,440 --> 01:05:34,840 INDIANA, ALL OVER THE PLACE, 1628 01:05:34,840 --> 01:05:36,120 REALLY, GEORGIA, TO EVALUATE 1629 01:05:36,120 --> 01:05:36,480 PATIENTS. 1630 01:05:36,480 --> 01:05:38,680 AND ONE DAY THERE WAS AN OLDER 1631 01:05:38,680 --> 01:05:40,240 GENTLEMAN IN THE STUDY, I 1632 01:05:40,240 --> 01:05:44,960 DROVE UP TO HIS HOUSE, HE 1633 01:05:44,960 --> 01:05:46,240 LIVED OUTSIDE CLARKSVILLE AND 1634 01:05:46,240 --> 01:05:47,800 HE HAD DONE, I THINK FAIRLY 1635 01:05:47,800 --> 01:05:49,880 WELL FOR HIS AGE ON THE 1636 01:05:49,880 --> 01:05:50,800 COGNITIVE TEST THAT HE HAD 1637 01:05:50,800 --> 01:05:54,400 TAKEN AND AS I PULLED IN TO 1638 01:05:54,400 --> 01:06:01,000 HIS DRIVEWAY, KIND OF A 1639 01:06:01,000 --> 01:06:02,400 RECIVIL -- RESILIENT WORLD WAR 1640 01:06:02,400 --> 01:06:04,120 II VET, NOT MANY OF THOSE LEFT 1641 01:06:04,120 --> 01:06:09,960 BUT HE WAS ALIVE, 87, HAD A 1642 01:06:09,960 --> 01:06:11,240 SLEDGEHAMMER, WAS STANDING 1643 01:06:11,240 --> 01:06:13,760 BEHIND AN OLD SEDAN AND I SAID 1644 01:06:13,760 --> 01:06:14,600 MR. JOHNSON, WHAT ARE YOU 1645 01:06:14,600 --> 01:06:17,000 DOING AND HE SAID I AM TRYING 1646 01:06:17,000 --> 01:06:18,960 TO POUND THE DENTS OUT OF THE 1647 01:06:18,960 --> 01:06:21,080 BUMPER IN MY CAR AND I SAID 1648 01:06:21,080 --> 01:06:23,040 YOU KNOW PROBABLY NOT A GOOD 1649 01:06:23,040 --> 01:06:25,000 IDEA, I CAN HELP YOU OR 1650 01:06:25,000 --> 01:06:26,200 WHATEVER AND I SAID WHAT IS 1651 01:06:26,200 --> 01:06:27,560 GOING ON AND HE SAID YOU KNOW 1652 01:06:27,560 --> 01:06:30,320 I HAD A CAR ACCIDENT, BACKED 1653 01:06:30,320 --> 01:06:32,960 INTO A CAR AND STARTED HAVING 1654 01:06:32,960 --> 01:06:34,560 A LOT OF CAR ACCIDENTS AND 1655 01:06:34,560 --> 01:06:37,560 THAT REALLY STRUCK ME AND 1656 01:06:37,560 --> 01:06:38,520 STAYED WITH ME, HIS STORY, 1657 01:06:38,520 --> 01:06:40,240 BECAUSE THIS WAS A GENTLEMAN 1658 01:06:40,240 --> 01:06:43,800 WHO MAY NOT HAVE BEEN IMPAIRED 1659 01:06:43,800 --> 01:06:45,640 ON COGNITIVE TESTING BUT WITH 1660 01:06:45,640 --> 01:06:46,680 REGARD TO DAY-TO-DAY 1661 01:06:46,680 --> 01:06:47,720 FUNCTIONING, HE WAS AND THIS 1662 01:06:47,720 --> 01:06:50,000 IS A PROBLEM WE WILL TALK 1663 01:06:50,000 --> 01:06:55,160 ABOUT AND THE PARADOX SHIFT 1664 01:06:55,160 --> 01:07:03,120 WE WILL GET INTO, HOW TO LOOK 1665 01:07:03,120 --> 01:07:04,200 AT COGNITIVE TESTING. 1666 01:07:04,200 --> 01:07:06,400 SO WHAT DO CURRENT APPROACHES 1667 01:07:06,400 --> 01:07:08,560 TO COGNITIVE TESTING DO WELL? 1668 01:07:08,560 --> 01:07:10,360 THERE ARE SOME THINGS THEY DO 1669 01:07:10,360 --> 01:07:10,760 WELL. 1670 01:07:10,760 --> 01:07:12,800 THEY ARE REALLY GOOD AT 1671 01:07:12,800 --> 01:07:15,440 DESCRIBING HOW DIFFERENT AN 1672 01:07:15,440 --> 01:07:17,960 INDIVIDUAL'S PERFORMANCE IS 1673 01:07:17,960 --> 01:07:20,280 THAN IT IS EXPECTED TO BE. 1674 01:07:20,280 --> 01:07:25,480 SO THERE IS THE JOHN Q.PUBLIC 1675 01:07:25,480 --> 01:07:27,680 PATIENT BASED ON THEIR 1676 01:07:27,680 --> 01:07:29,480 DEMOGRAPHICS, THIS IS HOW THEY 1677 01:07:29,480 --> 01:07:32,120 ARE SUPPOSED TO DO WITHIN 1678 01:07:32,120 --> 01:07:34,280 THESE NORMS AND IF THEY FALL 1679 01:07:34,280 --> 01:07:35,680 WITHIN THAT RANGE, WE WILL 1680 01:07:35,680 --> 01:07:38,840 CALL THEM NORMAL AND IF THEY 1681 01:07:38,840 --> 01:07:42,160 FALL OUTSIDE, WE WILL CALL HIM 1682 01:07:42,160 --> 01:07:43,720 THIS DISPARATE. 1683 01:07:43,720 --> 01:07:48,600 THIS APPROACH WORKS VERY WELL 1684 01:07:48,600 --> 01:07:51,040 DETERMINING HOW SOMEONE IS 1685 01:07:51,040 --> 01:07:52,840 WITHIN EXPECTED NORMS. 1686 01:07:52,840 --> 01:07:56,920 THE OTHER THING IT DOES IS 1687 01:07:56,920 --> 01:07:58,120 IDENTIFY THINGS THAT THE 1688 01:07:58,120 --> 01:07:59,320 INDIVIDUAL DOES WELL. 1689 01:07:59,320 --> 01:08:00,840 THE OTHER THING THE APPROACH 1690 01:08:00,840 --> 01:08:04,480 IS GOING TO DO IS DO WELL 1691 01:08:04,480 --> 01:08:05,680 HIGHLIGHTING RELATIVE 1692 01:08:05,680 --> 01:08:06,560 STRENGTHS AND WEAKNESSES. 1693 01:08:06,560 --> 01:08:08,960 IT WILL SHOW JOHN AND JAME 1694 01:08:08,960 --> 01:08:11,560 DOUGH ARE GREAT AT PROCESSING 1695 01:08:11,560 --> 01:08:13,640 SPEEDS, LESS GOOD AT EXECUTIVE 1696 01:08:13,640 --> 01:08:14,960 FUNCTIONS, MAJOR PROBLEMS WITH 1697 01:08:14,960 --> 01:08:17,760 WORKING MEMORY, IT WILL SHOW 1698 01:08:17,760 --> 01:08:20,240 THE STRENGTHS AND WEAKNESSES 1699 01:08:20,240 --> 01:08:22,880 AND CHARACTERIZE CHANGE OVER 1700 01:08:22,880 --> 01:08:23,480 TIME. 1701 01:08:23,480 --> 01:08:27,000 OFTEN WE DO STUDIES AT THREE 1702 01:08:27,000 --> 01:08:28,920 MONTHS, SIX MONTHS, 12 MONTHS, 1703 01:08:28,920 --> 01:08:31,800 TWO, THREE YEARS AND OFTEN 1704 01:08:31,800 --> 01:08:33,360 TIME CHARACTERIZE THEM BY 1705 01:08:33,360 --> 01:08:34,440 THESE APPROACHES. 1706 01:08:34,440 --> 01:08:34,840 NEXT SLIDE. 1707 01:08:34,840 --> 01:08:39,320 BUT THERE IS A DOWN SIDE. 1708 01:08:39,320 --> 01:08:42,040 THIS KIP CALL BATTERY BASED 1709 01:08:42,040 --> 01:08:44,520 APPROACH DOES SOME THINGS 1710 01:08:44,520 --> 01:08:46,520 SOMEWHAT LESS WELL AND THOSE 1711 01:08:46,520 --> 01:08:48,640 ARE THAT COMMON COGNITIVE 1712 01:08:48,640 --> 01:08:50,800 TESTS OFTEN FAIL TO RESPOND TO 1713 01:08:50,800 --> 01:08:51,640 REAL WORLD CHALLENGES AND 1714 01:08:51,640 --> 01:08:54,960 SITUATIONS IN THE WAY WE MIGHT 1715 01:08:54,960 --> 01:08:56,320 HOPE THEY DID. 1716 01:08:56,320 --> 01:08:58,960 I AM HOLDING IN MY HANDS, HAD 1717 01:08:58,960 --> 01:09:02,040 NOT THOUGHT OF USING THIS TOP, 1718 01:09:02,040 --> 01:09:03,880 THIS IS A FANCY APPARATUS AND 1719 01:09:03,880 --> 01:09:06,280 BASICALLY WHAT YOU DO IS MOVE 1720 01:09:06,280 --> 01:09:08,640 THESE DISKS -- I AM VIOLATING 1721 01:09:08,640 --> 01:09:09,480 SOME RULES HERE. 1722 01:09:09,480 --> 01:09:11,080 YOU MOVE THESE DISKS IN A 1723 01:09:11,080 --> 01:09:12,520 PARTICULAR WAY, IN A 1724 01:09:12,520 --> 01:09:13,560 PARTICULAR SEQUENCE AND THAT 1725 01:09:13,560 --> 01:09:18,080 IS GOING TO TELL ME HOW GOOD 1726 01:09:18,080 --> 01:09:19,920 YOU ARE AT PLANNING, THAT IS 1727 01:09:19,920 --> 01:09:20,840 THE THEORY. 1728 01:09:20,840 --> 01:09:22,560 AND THE POWER TEST AS FAR AS 1729 01:09:22,560 --> 01:09:24,960 COGNITIVE TESTS GO IS PRETTY 1730 01:09:24,960 --> 01:09:26,400 GOOD AT BEING PREDICTIVE BUT 1731 01:09:26,400 --> 01:09:28,080 STILL A STEP AWAY FROM THE 1732 01:09:28,080 --> 01:09:29,600 REAL WORLD. 1733 01:09:29,600 --> 01:09:32,080 SO THIS BATTERY BASED 1734 01:09:32,080 --> 01:09:33,680 APPROACH, WHILE SOMETIMES 1735 01:09:33,680 --> 01:09:36,000 LOVELY, IS PERHAPS NOT AS 1736 01:09:36,000 --> 01:09:37,240 PREDICTIVE OF PERFORMANCE THAT 1737 01:09:37,240 --> 01:09:39,680 IS WE MIGHT LIKE IT TO BE OF 1738 01:09:39,680 --> 01:09:40,040 FUNCTION. 1739 01:09:40,040 --> 01:09:42,000 AND YOU KNOW WE HAVE HAD A 1740 01:09:42,000 --> 01:09:44,720 REVOLUTION THAT IS ONGOING AND 1741 01:09:44,720 --> 01:09:46,160 IS LOVELY OF INTEGRATING 1742 01:09:46,160 --> 01:09:47,640 PATIENTS INTO THE WORK THAT WE 1743 01:09:47,640 --> 01:09:58,200 DO, IT IS LONG OVERDUE, NEED 1744 01:09:58,480 --> 01:10:02,800 TO DO BETTER BUT WE'RE HEADING 1745 01:10:02,800 --> 01:10:04,040 IN THE RIGHT DIRECTION AND 1746 01:10:04,040 --> 01:10:06,400 WHEN YOU TALK TO PATIENTS 1747 01:10:06,400 --> 01:10:08,960 ABOUT IMPAIRMENT, THEY ARE NOT 1748 01:10:08,960 --> 01:10:10,880 CONCERNED ABOUT COGNITIVE 1749 01:10:10,880 --> 01:10:12,840 IMPAIRMENT, THEY ARE CONCERNED 1750 01:10:12,840 --> 01:10:14,040 ABOUT COGNITIVE IMPAIRMENT IN 1751 01:10:14,040 --> 01:10:15,640 THE TERMS OF FUNCTION, 1752 01:10:15,640 --> 01:10:17,880 FUNCTION IS ALL THEY CARE 1753 01:10:17,880 --> 01:10:20,360 ABOUT. 1754 01:10:20,360 --> 01:10:23,760 SO THE COGNITIVE TESTS 1755 01:10:23,760 --> 01:10:25,840 PREDICTOR FAIL AT FUNCTION AND 1756 01:10:25,840 --> 01:10:27,360 THE GREATEST CONCERN FOR 1757 01:10:27,360 --> 01:10:28,600 PATIENTS S-R NOT IMPAIRMENT 1758 01:10:28,600 --> 01:10:31,240 BUT IT IS FUNCTION. 1759 01:10:31,240 --> 01:10:32,400 CURRENT APPROACHES, THE OTHER 1760 01:10:32,400 --> 01:10:34,920 COMMENT I WOULD MAKE, TREAT 1761 01:10:34,920 --> 01:10:36,160 IMPAIRMENT AS ALL OR NOTHING 1762 01:10:36,160 --> 01:10:40,360 AND I WOULD MAKE KIND OF A 1763 01:10:40,360 --> 01:10:41,520 GENERATIONAL BROAD BRUSH 1764 01:10:41,520 --> 01:10:42,520 COMMENT HERE ABOUT THE 1765 01:10:42,520 --> 01:10:45,520 EVOLUTION OF THE WORK IN 1766 01:10:45,520 --> 01:10:46,960 COGNITIVE IMPAIRMENT OF ICU 1767 01:10:46,960 --> 01:10:51,080 SURVIVORS, IT USED TO BE IN 1768 01:10:51,080 --> 01:10:55,200 2001, 2, 3, 4, 2010 EVEN, MONA 1769 01:10:55,200 --> 01:10:59,280 HOPKINS WOULD GO TO A MEETING 1770 01:10:59,280 --> 01:11:00,880 AND SAY 30 PERCENT OF THE 1771 01:11:00,880 --> 01:11:03,360 PEOPLE WEREN'T THERE OR 20 OR 1772 01:11:03,360 --> 01:11:06,160 40 AND PEOPLE WOULD SAY WOW, 1773 01:11:06,160 --> 01:11:07,400 THAT IS AMAZING, THERE WOULD 1774 01:11:07,400 --> 01:11:10,920 BE ALL THESE OOS AND AHS AND 1775 01:11:10,920 --> 01:11:13,440 PEOPLE WOULD BE IMPRESSED BY 1776 01:11:13,440 --> 01:11:13,720 THAT. 1777 01:11:13,720 --> 01:11:18,240 IN 2023 WE NEED TO MOVE BEYOND 1778 01:11:18,240 --> 01:11:25,120 SIMPLY REPORTING FOR THE 47TH 1779 01:11:25,120 --> 01:11:27,920 TIME, WOW, COGNITIVE 1780 01:11:27,920 --> 01:11:29,400 APPROACHES NEED TO MEASURE 1781 01:11:29,400 --> 01:11:30,920 PEOPLE WHO ARE IMPAIRED. 1782 01:11:30,920 --> 01:11:34,760 WE NEED TO UNDERSTAND 1783 01:11:34,760 --> 01:11:37,400 IMPAIRMENT IMPACTS PEOPLE 1784 01:11:37,400 --> 01:11:38,200 DIFFERENTIALLY AND THINK HARD 1785 01:11:38,200 --> 01:11:39,240 OF THIS. 1786 01:11:39,240 --> 01:11:42,560 OH MY GOSH, SPEAKER HAS FOUR 1787 01:11:42,560 --> 01:11:43,600 MINUTES REMAINING. 1788 01:11:43,600 --> 01:11:46,120 SO IT COULD BE HOW WELL YOU 1789 01:11:46,120 --> 01:11:47,280 NOVEMBER BAIT THE TIME YOU 1790 01:11:47,280 --> 01:11:48,320 HAVE. 1791 01:11:48,320 --> 01:11:50,880 SO MILD COGNITIVE IMPAIRMENT 1792 01:11:50,880 --> 01:11:56,000 PLUS A FEW RESOURCES IN THE 1793 01:11:56,000 --> 01:11:59,160 CONTEXT OF HIGH RESILIENCE 1794 01:11:59,160 --> 01:12:01,120 EQUALS SIGNIFICANT FUNCTIONAL 1795 01:12:01,120 --> 01:12:02,160 IMPAIRMENT. 1796 01:12:02,160 --> 01:12:04,480 SIGNIFICANT COGNITIVE 1797 01:12:04,480 --> 01:12:07,160 IMPAIRMENT AND SUBSTANTIAL 1798 01:12:07,160 --> 01:12:09,360 RESOURCES EQUALS RELATIVELY 1799 01:12:09,360 --> 01:12:10,400 MILD COGNITIVE IMPAIRMENT. 1800 01:12:10,400 --> 01:12:13,400 NEXT SLIDE, PLEASE. 1801 01:12:13,400 --> 01:12:16,000 AND THE IMPAIRMENT VARIOUS 1802 01:12:16,000 --> 01:12:16,400 DRAMATICALLY. 1803 01:12:16,400 --> 01:12:19,040 IMPAIRMENT DURING A 1804 01:12:19,040 --> 01:12:20,880 DEVELOPMENTAL TRAJECTORY IN A 1805 01:12:20,880 --> 01:12:23,200 YOUNG ADULT IS SOMEWHAT MORE 1806 01:12:23,200 --> 01:12:26,600 IMPACTFUL THAN IN SOMEONE WHO 1807 01:12:26,600 --> 01:12:30,320 IS 92, PERSONS WORKING IN 1808 01:12:30,320 --> 01:12:31,080 COGNITIVELY DEMANDING JOBS 1809 01:12:31,080 --> 01:12:33,280 VERSUS JOBS THAT ARE SIMPLE 1810 01:12:33,280 --> 01:12:35,360 AND REPETITIVE. 1811 01:12:35,360 --> 01:12:37,880 IMPAIRMENT IN PEOPLE IN 1812 01:12:37,880 --> 01:12:39,200 INDIVIDUALIST AND COLLECTIST 1813 01:12:39,200 --> 01:12:41,160 JOBS, VERY DIFFERENT. 1814 01:12:41,160 --> 01:12:43,320 NEXT SLIDE, PLEASE. 1815 01:12:43,320 --> 01:12:45,040 IS COGNITIVE IMPAIRMENT DENINE 1816 01:12:45,040 --> 01:12:45,720 OR CONCERNING? 1817 01:12:45,720 --> 01:12:50,320 WE NEED TO FIGURE THIS OUT. 1818 01:12:50,320 --> 01:12:51,200 NEXT, SLIDE PLEASE. 1819 01:12:51,200 --> 01:12:53,600 I SAW A PATIENT, VERY 1820 01:12:53,600 --> 01:12:57,600 ACOMMUNITY, SAID I DON'T NEED 1821 01:12:57,600 --> 01:12:58,280 COGNITIVELY HABILITATION, MY 1822 01:12:58,280 --> 01:13:01,880 PLAN IS JUST TO HIRE A 1823 01:13:01,880 --> 01:13:06,800 FULL-TIME 14/7 PERSONAL 1824 01:13:06,800 --> 01:13:07,400 ASSISTANCE. 1825 01:13:07,400 --> 01:13:09,560 SO THERE IS SOMETHING CALLED 1826 01:13:09,560 --> 01:13:11,320 THE BEST KEPT SECRET FESTIVAL, 1827 01:13:11,320 --> 01:13:14,320 I GUESS IT WOULD HELD IN 1828 01:13:14,320 --> 01:13:17,200 JUNE 2013, I DIDN'T GO BUT 1829 01:13:17,200 --> 01:13:25,120 NOURISH KICK COL GEE'S -- 1830 01:13:25,120 --> 01:13:26,400 NEUROPSYCHOLOGY'S SECRET, NEXT 1831 01:13:26,400 --> 01:13:33,640 SLIDE PLEASE, IS IN THE 1832 01:13:33,640 --> 01:13:35,640 CONTEXT OF NEUROPSYCHOLOGICAL 1833 01:13:35,640 --> 01:13:37,000 HITTING THE WALL. 1834 01:13:37,000 --> 01:13:39,560 NEXT SLIDE PLEASE. 1835 01:13:39,560 --> 01:13:40,240 OFFENSIVE LINEMEN NEVER RUN 1836 01:13:40,240 --> 01:13:41,920 40 YARDS YET IT IS THE 1837 01:13:41,920 --> 01:13:43,320 CORNERSTONE OF THE NFL 1838 01:13:43,320 --> 01:13:44,120 COMBINE. 1839 01:13:44,120 --> 01:13:45,040 WHY IS THAT? 1840 01:13:45,040 --> 01:13:46,640 DOESN'T SEEM LIKE WE NEED TO 1841 01:13:46,640 --> 01:13:50,000 KNOW HOW FAST AN OFFENSIVE 1842 01:13:50,000 --> 01:13:52,400 LINEMAN RUNS 40 YARDS WHEN HE 1843 01:13:52,400 --> 01:13:53,800 ONLY RUNS 5 YARDS. 1844 01:13:53,800 --> 01:13:54,560 NEXT SLIDE. 1845 01:13:54,560 --> 01:13:58,320 THE POINT IS WE NEED TO FOCUS 1846 01:13:58,320 --> 01:14:02,520 LESS ON THIS BINARY ALL OR 1847 01:14:02,520 --> 01:14:05,080 NOTHING CLASSIC APPROACH 1848 01:14:05,080 --> 01:14:06,240 TESTING USING THINGS LIKE THE 1849 01:14:06,240 --> 01:14:09,080 POWER TEST AND FOCUS MORE ON 1850 01:14:09,080 --> 01:14:09,880 MEASURES WHERE THEY GENERALIZE 1851 01:14:09,880 --> 01:14:11,560 TO THE REAL WORLD. 1852 01:14:11,560 --> 01:14:12,840 NEXT SLIDE, PLEASE. 1853 01:14:12,840 --> 01:14:13,920 NEXT SLIDE, PLEASE. 1854 01:14:13,920 --> 01:14:14,640 NEXT SLIDE, PLEASE. 1855 01:14:14,640 --> 01:14:16,200 I AM SKIPPING A FEW THINGS 1856 01:14:16,200 --> 01:14:17,680 HERE. 1857 01:14:17,680 --> 01:14:21,080 TIME FOR A PARADIGM SHIFT. 1858 01:14:21,080 --> 01:14:27,480 THIS IS TOMMY KOOMBS, WROTE WE 1859 01:14:27,480 --> 01:14:29,400 NEED A PARADIGM SHIFT. 1860 01:14:29,400 --> 01:14:30,280 NEXT SLIDE, PLEASE. 1861 01:14:30,280 --> 01:14:34,200 WE NEED TO FIGURE OUT CAN YOU 1862 01:14:34,200 --> 01:14:35,360 OPERATE A BACKHOE? 1863 01:14:35,360 --> 01:14:35,880 NEXT SLIDE, PLEASE. 1864 01:14:35,880 --> 01:14:37,640 ARE YOU FIT TO DRIVE? 1865 01:14:37,640 --> 01:14:39,480 NEXT SLIDE, CAN YOU CALCULATE 1866 01:14:39,480 --> 01:14:40,440 YOUR TAXES? 1867 01:14:40,440 --> 01:14:43,320 CAN YOU FIGURE OUT COMPLEX 1868 01:14:43,320 --> 01:14:44,080 FINANCIAL DATA? 1869 01:14:44,080 --> 01:14:44,680 NEXT SLIDE. 1870 01:14:44,680 --> 01:14:48,320 CAN YOU WORK ON AN ASSEMBLY 1871 01:14:48,320 --> 01:14:48,800 LINE? 1872 01:14:48,800 --> 01:14:52,560 THIS IS LUCY AND ETHYL HERE IF 1873 01:14:52,560 --> 01:14:53,400 YOU REMEMBER. 1874 01:14:53,400 --> 01:14:57,560 CRITICALLY CAN YOU REPORT 1875 01:14:57,560 --> 01:14:57,880 SURGERY. 1876 01:14:57,880 --> 01:14:58,840 CARLA REFERENCED A DOCTOR, 1877 01:14:58,840 --> 01:15:00,800 DIDN'T KNOW THE TIME OR THE 1878 01:15:00,800 --> 01:15:01,200 PRESIDENT. 1879 01:15:01,200 --> 01:15:02,920 DO WE WANT HIM TO DO SURGERY? 1880 01:15:02,920 --> 01:15:04,040 I DON'T THINK SO. 1881 01:15:04,040 --> 01:15:06,040 DOES THAT MEAN HE CAN'T DO 1882 01:15:06,040 --> 01:15:06,440 ANYTHING? 1883 01:15:06,440 --> 01:15:07,520 I DON'T THINK SO. 1884 01:15:07,520 --> 01:15:09,320 NEXT SLIDE, PLEASE. 1885 01:15:09,320 --> 01:15:11,960 CAN YOU MANAGE A COMPLEX 1886 01:15:11,960 --> 01:15:12,520 MEDICATION REGIMEN? 1887 01:15:12,520 --> 01:15:14,040 I AM JUST ABOUT OUT OF TIME SO 1888 01:15:14,040 --> 01:15:16,000 WHAT IS THE POINT I WOULD MAKE 1889 01:15:16,000 --> 01:15:16,280 HERE? 1890 01:15:16,280 --> 01:15:17,920 THE POINT I WOULD MAKE HERE IS 1891 01:15:17,920 --> 01:15:22,160 WE NEED TO SHIFT OUR FOCUS 1892 01:15:22,160 --> 01:15:24,200 FROM THE TRADITIONAL COGNITIVE 1893 01:15:24,200 --> 01:15:27,120 TESTS TO REAL WORLD OVERTURES 1894 01:15:27,120 --> 01:15:29,600 WHERE WE FIGURE OUT WHEN YOU 1895 01:15:29,600 --> 01:15:32,400 GO TO THE GROCERY STORE, HOW 1896 01:15:32,400 --> 01:15:32,880 DO YOU NAVIGATE. 1897 01:15:32,880 --> 01:15:35,520 WHEN YOU ARE IN YOUR CAR 1898 01:15:35,520 --> 01:15:37,120 DRIVING, HOW DO YOU MANAGE 1899 01:15:37,120 --> 01:15:39,200 THAT, WHEN YOU ARE IN SOCIAL 1900 01:15:39,200 --> 01:15:40,440 SITUATIONS, HOW DO YOU DO WITH 1901 01:15:40,440 --> 01:15:43,920 THAT AND THIS IS WHERE WE WILL 1902 01:15:43,920 --> 01:15:45,360 MEASURE A MEANINGFUL PARADIGM. 1903 01:15:45,360 --> 01:15:47,880 IF I FOLLOW A PATIENT IMPAIRED 1904 01:15:47,880 --> 01:15:49,480 IN A GROCERY STORE WITH A 1905 01:15:49,480 --> 01:15:50,960 LEGAL PAD AND GIVE HIM 1906 01:15:50,960 --> 01:15:52,200 INSTRUCTIONS AND I AM CAREFUL 1907 01:15:52,200 --> 01:15:54,800 TO NOTE WHAT HE DID AND DIDN'T 1908 01:15:54,800 --> 01:15:56,400 DO IN FOLLOWING THOSE 1909 01:15:56,400 --> 01:15:58,120 INSTRUCTIONS, HOW DO YOU 1910 01:15:58,120 --> 01:16:00,440 TRANSLATE THAT INTO A SCORE? 1911 01:16:00,440 --> 01:16:03,080 SO THE GAPS HERE ARE WE ARE 1912 01:16:03,080 --> 01:16:06,840 GREAT AT MEASURING COGNITIVE 1913 01:16:06,840 --> 01:16:08,040 IMPAIRMENT USING NEUROPSYCH 1914 01:16:08,040 --> 01:16:08,440 TECHNOLOGY. 1915 01:16:08,440 --> 01:16:10,720 WE ARE LESS GOOD THOUGH AT 1916 01:16:10,720 --> 01:16:12,640 MEASURING FUNCTION BECAUSE 1917 01:16:12,640 --> 01:16:14,040 TESTS DON'T NECESSARILY DO 1918 01:16:14,040 --> 01:16:14,320 THAT. 1919 01:16:14,320 --> 01:16:16,600 THE HIGH RISK HIGH REWARD 1920 01:16:16,600 --> 01:16:18,520 OPPORTUNITIES IS TO SHIFT 1921 01:16:18,520 --> 01:16:20,120 THEIR PAID DIME ENTIRELY AND 1922 01:16:20,120 --> 01:16:22,680 BEGIN TO FOCUS ON FUNCTION 1923 01:16:22,680 --> 01:16:24,400 USING NOVEL TOOLS AND 1924 01:16:24,400 --> 01:16:25,200 TECHNIQUES GETTING AT WHAT IS 1925 01:16:25,200 --> 01:16:27,720 HAPPENING IN THE REAL WORLD -- 1926 01:16:27,720 --> 01:16:28,320 PARADIGM. 1927 01:16:28,320 --> 01:16:31,280 THANK YOU FOR YOUR ATTENTION. 1928 01:16:31,280 --> 01:16:32,760 >>THANK YOU, TERRORIST JACKS 1929 01:16:32,760 --> 01:16:33,040 SOP. 1930 01:16:33,040 --> 01:16:36,560 AMAZING AND A TRULY IMPRESSIVE 1931 01:16:36,560 --> 01:16:38,160 AMOUNT OF WORK COVERED IN THE 1932 01:16:38,160 --> 01:16:41,400 LAST FOUR MINUTES THERE. 1933 01:16:41,400 --> 01:16:44,960 IN THE ONE MINUTE WE HAVE 1934 01:16:44,960 --> 01:16:47,160 REMAINING, I HAVE A QUESTION 1935 01:16:47,160 --> 01:16:49,760 FROM THE CHAT. 1936 01:16:49,760 --> 01:16:50,800 PERHAPS FUNCTIONAL EVALUATIONS 1937 01:16:50,800 --> 01:16:52,400 BETTER RELATE TO TREATMENT 1938 01:16:52,400 --> 01:16:52,800 STRATEGIES. 1939 01:16:52,800 --> 01:16:54,880 SO THIS WILL BE SPECIFIC TO 1940 01:16:54,880 --> 01:16:57,440 BIOLOGY SO I CAN PAIR FRAYS. 1941 01:16:57,440 --> 01:16:59,920 DO WE KNOW WHETHER THE 1942 01:16:59,920 --> 01:17:01,680 COGNITIVE TEST OR FUNCTIONAL 1943 01:17:01,680 --> 01:17:03,000 TESTS ARE REFLECTIVE OF 1944 01:17:03,000 --> 01:17:03,320 BIOLOGY? 1945 01:17:03,320 --> 01:17:04,120 >>THAT IS A GREAT QUESTION. 1946 01:17:04,120 --> 01:17:05,560 I DON'T KNOW IF WE KNOW THAT. 1947 01:17:05,560 --> 01:17:07,560 I THINK WOULD HE DO NEED TO 1948 01:17:07,560 --> 01:17:08,080 FIGURE THAT OUT. 1949 01:17:08,080 --> 01:17:09,960 I THINK WE KNOW THE FUNCTIONAL 1950 01:17:09,960 --> 01:17:14,720 TESTS ARE WHAT THE PATIENTS 1951 01:17:14,720 --> 01:17:16,360 THEMSELVES GRAVITATE TO, BUT 1952 01:17:16,360 --> 01:17:19,440 WHETHER THEY REFLECT BIOLOGY 1953 01:17:19,440 --> 01:17:22,280 BETTER, I DON'T THINK WE 1954 01:17:22,280 --> 01:17:23,240 NECESSARILY KNOW. 1955 01:17:23,240 --> 01:17:28,280 >> AND OF COURSE THE 1956 01:17:28,280 --> 01:17:29,880 FASCINATION WITH ALZHEIMER'S, 1957 01:17:29,880 --> 01:17:33,920 COULDN'T HELP BUT SEE SOME 1958 01:17:33,920 --> 01:17:34,920 COMPARISONS HERE. 1959 01:17:34,920 --> 01:17:40,880 SO DOCTOR JACKSON, THANK YOU. 1960 01:17:40,880 --> 01:17:47,680 NEXT WE HAVE Dr. CONNOLLY, 1961 01:17:47,680 --> 01:17:50,800 SURVIVORSHIP OF CRITICAL ILL 1962 01:17:50,800 --> 01:17:54,440 PATIENTS AND CLINICAL 1963 01:17:54,440 --> 01:17:56,000 METHODOLOGY AROUND 1964 01:17:56,000 --> 01:17:56,480 REHABILITATION AND 1965 01:17:56,480 --> 01:17:58,800 INTERVENTION AND AS WELL AS 1966 01:17:58,800 --> 01:18:02,680 THAT STUFF, FINDING OUTCOMES 1967 01:18:02,680 --> 01:18:11,320 AND RETRO DUESABLE OUTCOMES 1968 01:18:11,320 --> 01:18:15,680 AND FINDING PATIENTS TO 1969 01:18:15,680 --> 01:18:16,280 REVERSE THESE OUTCOMES. 1970 01:18:16,280 --> 01:18:18,240 THANK YOU VERY MUCH. 1971 01:18:18,240 --> 01:18:21,640 >>THANK YOU FOR BEING A PART 1972 01:18:21,640 --> 01:18:24,600 OF THIS MEETING FOR THE NIH IN 1973 01:18:24,600 --> 01:18:29,520 WHAT I WOULD CALL A WORKSHOP. 1974 01:18:29,520 --> 01:18:35,160 SO YES, I AM DELIGHTED TO TALK 1975 01:18:35,160 --> 01:18:36,000 ABOUT MEASURING MUSCLES AND 1976 01:18:36,000 --> 01:18:36,360 FUNCTIONS. 1977 01:18:36,360 --> 01:18:39,600 IF YOU CAN SEE MY SLIDES? 1978 01:18:39,600 --> 01:18:40,600 >>WE CANNOT. 1979 01:18:40,600 --> 01:18:49,480 WHAT WE CURRENTLY SEE IS 1980 01:18:49,480 --> 01:18:50,280 WINDOWS DISPLAY MANAGER. 1981 01:18:50,280 --> 01:18:51,960 >>OKAY, THAT IS MORE LIKE IT. 1982 01:18:51,960 --> 01:18:53,440 THANK YOU VERY MUCH. 1983 01:18:53,440 --> 01:18:54,000 NEXT SLIDE, PLEASE. 1984 01:18:54,000 --> 01:18:56,920 I HAVE A COUPLE OF DISCLOSURES 1985 01:18:56,920 --> 01:18:59,360 BUT NONE OF THEM ARE RELEVANT 1986 01:18:59,360 --> 01:19:04,440 TO TODAY'S PRESENTATION. 1987 01:19:04,440 --> 01:19:06,600 NEXT SLIDE, PLEASE. 1988 01:19:06,600 --> 01:19:07,000 NEXT SLIDE. 1989 01:19:07,000 --> 01:19:07,720 THANK YOU. 1990 01:19:07,720 --> 01:19:11,000 LET'S START WITH WHAT DO WE 1991 01:19:11,000 --> 01:19:13,920 KNOW AROUND MEASURING MUSCLE 1992 01:19:13,920 --> 01:19:15,000 FUNCTION. 1993 01:19:15,000 --> 01:19:16,880 NEXT SLIDE PLEASE. 1994 01:19:16,880 --> 01:19:18,760 THESE WILL NOT BE UNFAMILIAR 1995 01:19:18,760 --> 01:19:21,960 TO ANYONE ON THE CALL AND 1996 01:19:21,960 --> 01:19:25,400 THESE ARE SELECT EXAMPLES OF 1997 01:19:25,400 --> 01:19:27,840 SURVIVORS WHO EXPERIENCED 1998 01:19:27,840 --> 01:19:31,000 PRONOUNCED AND PROTRACTED 1999 01:19:31,000 --> 01:19:33,520 PHYSICAL IMPAIRMENT AND SOME 2000 01:19:33,520 --> 01:19:36,920 OF THE WORK DONE AROUND FIVE 2001 01:19:36,920 --> 01:19:43,920 YEARS WHERE YOU HAVE THREE 2002 01:19:43,920 --> 01:19:49,680 QUARTERS OF THE COGNITIVE 2003 01:19:49,680 --> 01:19:51,320 FACTORS AND HERE LOOKING AT 2004 01:19:51,320 --> 01:19:55,240 THE SAME TWO MEASURES, AT THE 2005 01:19:55,240 --> 01:19:57,840 TOP I STRESS THE MUSCLE 2006 01:19:57,840 --> 01:19:59,280 STRENGTH IN THE SCORE. 2007 01:19:59,280 --> 01:20:01,240 JUST TO KEEP IN MIND THE 2008 01:20:01,240 --> 01:20:03,520 BARRIERS TO RECOVERY AS YOU 2009 01:20:03,520 --> 01:20:06,680 SEE ACROSS THESE THREE 2010 01:20:06,680 --> 01:20:09,480 DIFFERENT SECTIONS, THE MUSCLE 2011 01:20:09,480 --> 01:20:12,880 STRENGTH KIND OF PALES IN 2012 01:20:12,880 --> 01:20:13,280 RECOVERY. 2013 01:20:13,280 --> 01:20:17,520 AND THEN IN THE MOST RECENT 2014 01:20:17,520 --> 01:20:23,320 GROUP WHERE IT HAS BEEN 2015 01:20:23,320 --> 01:20:25,200 CHARACTERIZED WITH THE 2016 01:20:25,200 --> 01:20:28,360 PHENOTYPES, WHETHER THAT HAS A 2017 01:20:28,360 --> 01:20:30,080 PHYSICAL IMPAIRMENT AND WHAT 2018 01:20:30,080 --> 01:20:32,400 THEY SAW IS PHYSICAL 2019 01:20:32,400 --> 01:20:34,760 IMPAIRMENT WAS NOT EVIDENT IN 2020 01:20:34,760 --> 01:20:37,680 ALL CASES BUT IN CERTAIN 2021 01:20:37,680 --> 01:20:39,880 SUBTYPES AND I GUESS ONE OF 2022 01:20:39,880 --> 01:20:43,960 THE THINGS I HAVE LEARNED IN 2023 01:20:43,960 --> 01:20:45,440 THIS STUDY BETWEEN THE MUSCLE 2024 01:20:45,440 --> 01:20:47,880 STRENGTHS AND THE FISCAL 2025 01:20:47,880 --> 01:20:50,280 FUNCTIONS OUTCOMES THERE. 2026 01:20:50,280 --> 01:20:51,240 NEXT SLIDE, PLEASE. 2027 01:20:51,240 --> 01:20:55,320 SO IF WE KNOW THIS PHYSICAL 2028 01:20:55,320 --> 01:20:56,880 IMPAIRMENT EXISTS, WHAT ARE WE 2029 01:20:56,880 --> 01:20:57,960 PRETTY SURE OF. 2030 01:20:57,960 --> 01:20:59,040 NEXT SLIDE, PLEASE. 2031 01:20:59,040 --> 01:21:01,760 AND WE CAN BE PRETTY CERTAIN 2032 01:21:01,760 --> 01:21:03,920 MUSCLE FUNCTION HAS SOMETHING 2033 01:21:03,920 --> 01:21:07,200 TO DO WITH THIS AND THIS GRAPH 2034 01:21:07,200 --> 01:21:09,280 IS VERY ELEGANT IN SUMMARIZING 2035 01:21:09,280 --> 01:21:14,200 ALL THE PROBLEMS WE SEE IN A 2036 01:21:14,200 --> 01:21:16,440 TYPICAL MECHANIC CANNISTIC 2037 01:21:16,440 --> 01:21:17,920 LEVEL THAT EXPLAINS 2038 01:21:17,920 --> 01:21:20,000 NEUROMUSCULAR IMPAIRMENT WE 2039 01:21:20,000 --> 01:21:22,280 SEE IN PATIENTS AFTER CRITICAL 2040 01:21:22,280 --> 01:21:22,920 ILLNESS. 2041 01:21:22,920 --> 01:21:24,080 NEXT SLIDE, PLEASE. 2042 01:21:24,080 --> 01:21:25,680 SO IF WE THINK MUSCLE HAS 2043 01:21:25,680 --> 01:21:28,640 SOMETHING TO DO WITH IT AND IT 2044 01:21:28,640 --> 01:21:31,080 PROBABLY DOES, HOW GOOD ARE WE 2045 01:21:31,080 --> 01:21:35,960 AT MEASURING MUSCLE FUNCTION 2046 01:21:35,960 --> 01:21:36,960 IN CRITICALLY-ILL PATIENTS? 2047 01:21:36,960 --> 01:21:37,840 NEXT SLIDE, PLEASE. 2048 01:21:37,840 --> 01:21:39,720 AND THEN COMMON TECHNIQUES AND 2049 01:21:39,720 --> 01:21:42,200 MANY ON THE CALL WILL BE 2050 01:21:42,200 --> 01:21:45,080 FAMILIAR WITH THE WAYS WE 2051 01:21:45,080 --> 01:21:46,600 MEASURE MUSCLE FUNCTION SO 2052 01:21:46,600 --> 01:21:48,040 STARTING IN THE RIGHTHAND 2053 01:21:48,040 --> 01:21:58,640 CORNER OF THE SCREEN, YOU SEE 2054 01:21:59,520 --> 01:22:04,960 THE SEE THE ULTRASOUND VIEW -- 2055 01:22:04,960 --> 01:22:05,560 [INDISCERNIBLE] 2056 01:22:05,560 --> 01:22:08,560 AND ON THE RIGHTHAND SIDE 2057 01:22:08,560 --> 01:22:12,600 THERE, THE MUSCLE BIOPSY DATA, 2058 01:22:12,600 --> 01:22:15,040 SOME PERIPHERAL MUSCLE BUT THE 2059 01:22:15,040 --> 01:22:17,640 MUSCLE DATA EXISTS AND WE ARE 2060 01:22:17,640 --> 01:22:19,760 ABLE TO LOOK AT BIOLOGY TO SEE 2061 01:22:19,760 --> 01:22:22,640 EXACTLY WHAT IS HAPPENING TO 2062 01:22:22,640 --> 01:22:24,560 THE MUSCULAR STRENGTH. 2063 01:22:24,560 --> 01:22:26,480 ON THE RIGHTHAND SIDE IS THE 2064 01:22:26,480 --> 01:22:31,080 GRAPH OF MUSCLE TESTING AND 2065 01:22:31,080 --> 01:22:33,000 THIS IS OFTEN MISDIAGNOSED AND 2066 01:22:33,000 --> 01:22:39,520 CLEARLY ONE OF THE MAIN AREAS 2067 01:22:39,520 --> 01:22:46,600 HEEDING TO BETTER-- LEADING TO 2068 01:22:46,600 --> 01:22:47,560 BETTER OUTCOMES FOR 2069 01:22:47,560 --> 01:22:48,240 PATIENTS -- 2070 01:22:48,240 --> 01:22:48,720 [INDISCERNIBLE] 2071 01:22:48,720 --> 01:22:49,640 AND FINALLY IN THE BOTTOM 2072 01:22:49,640 --> 01:22:52,240 CORNER THERE YOU CAN SEE SOME 2073 01:22:52,240 --> 01:22:55,560 OF THE TABULATION DATA LOOKING 2074 01:22:55,560 --> 01:23:00,360 AT MUSCLE SOURCE AND CAPACITY 2075 01:23:00,360 --> 01:23:03,840 AND ABLE TO TAKE FROM IC 2076 01:23:03,840 --> 01:23:06,120 PATIENTS AND MEASURE WHAT WAS 2077 01:23:06,120 --> 01:23:07,160 THE DENSITY OF MUSCLES. 2078 01:23:07,160 --> 01:23:09,920 SO WE HAVE SEEN FOUR DIFFERENT 2079 01:23:09,920 --> 01:23:12,120 APPROACHES, THEY HAVE THEIR 2080 01:23:12,120 --> 01:23:16,440 PROS AND CONS, SOME OF THEM 2081 01:23:16,440 --> 01:23:16,760 HAVE. 2082 01:23:16,760 --> 01:23:17,240 [INDISCERNIBLE] 2083 01:23:17,240 --> 01:23:18,760 , CAVEAT OF BEING ABLE TO USE 2084 01:23:18,760 --> 01:23:20,600 ALL OF THEM, NEXT SLIDE, 2085 01:23:20,600 --> 01:23:20,960 PLEASE. 2086 01:23:20,960 --> 01:23:23,480 AND WHAT WE ARE PRETTY SURE IS 2087 01:23:23,480 --> 01:23:24,800 NONE IS COMPLETELY FIT FOR 2088 01:23:24,800 --> 01:23:26,360 PURPOSE TO TELL US THE 2089 01:23:26,360 --> 01:23:27,840 RELATIONSHIP BETWEEN MUSCLE 2090 01:23:27,840 --> 01:23:28,920 FUNCTION AND PHYSICAL 2091 01:23:28,920 --> 01:23:29,920 FUNCTIONING IN OUR PATIENTS 2092 01:23:29,920 --> 01:23:31,960 AND WE HAVE HEARD ALREADY THE 2093 01:23:31,960 --> 01:23:33,600 PHYSICAL FUNCTIONING IS THE 2094 01:23:33,600 --> 01:23:36,760 ABILITY TO DO SOMETHING WHICH 2095 01:23:36,760 --> 01:23:42,520 REALLY HEARTS TO PATIENTS THAN 2096 01:23:42,520 --> 01:23:47,960 ANY ISOLATED MEASUREMENT OF 2097 01:23:47,960 --> 01:23:48,320 FUNCTION. 2098 01:23:48,320 --> 01:23:50,160 AND SO THE CHALLENGES OF 2099 01:23:50,160 --> 01:23:55,880 CURRENT APPROACHES, THEY ALL 2100 01:23:55,880 --> 01:23:58,600 PROVIDE SOME DATA ON ISOLATED 2101 01:23:58,600 --> 01:24:03,920 ASPECT OF MUSCLE FUNCTION BUT 2102 01:24:03,920 --> 01:24:07,440 THEY DON'T NECESSARILY 2103 01:24:07,440 --> 01:24:10,880 INTERRELATE OR WHAT WE ARE 2104 01:24:10,880 --> 01:24:16,120 MEASURING, DO WE KNOW WHAT 2105 01:24:16,120 --> 01:24:22,040 THAT MEASUREMENT MEANS. 2106 01:24:22,040 --> 01:24:22,360 AND-- 2107 01:24:22,360 --> 01:24:22,800 [INDISCERNIBLE] 2108 01:24:22,800 --> 01:24:27,640 AND IN ORDER TO BE ABLE TO 2109 01:24:27,640 --> 01:24:34,840 TEST THE PATIENTS ACCURATELY. 2110 01:24:34,840 --> 01:24:37,600 DO EACH OF THE MEASURES 2111 01:24:37,600 --> 01:24:45,080 CORRELATE WITH THE OTHERS. 2112 01:24:45,080 --> 01:24:46,240 THE GIRLIZE-ABILITY, WHAT IS 2113 01:24:46,240 --> 01:24:49,080 THAT ACROSS PATIENTS AND WE 2114 01:24:49,080 --> 01:24:56,080 WILL PICK THAT UP IN ONE OF 2115 01:24:56,080 --> 01:24:57,200 THE NEXT SLIDES. 2116 01:24:57,200 --> 01:25:01,160 YOU CAN APPRECIATE THE 2117 01:25:01,160 --> 01:25:05,680 DIFFERENCE BETWEEN MUSCLE 2118 01:25:05,680 --> 01:25:10,880 TESTING, NO EQUIPMENT REQUIRED 2119 01:25:10,880 --> 01:25:15,240 TO DO SOME OF THOSE QUICK 2120 01:25:15,240 --> 01:25:19,400 STUDIES AND WHETHER THAT IS 2121 01:25:19,400 --> 01:25:20,840 USEFUL FOR RELIABLE AND SOME 2122 01:25:20,840 --> 01:25:27,320 OF THE DATA WE GET FROM THE 2123 01:25:27,320 --> 01:25:31,080 STUDIES, DO WE HAVE A 2124 01:25:31,080 --> 01:25:32,680 TREATMENT PLAN, WHICH MUSCLE 2125 01:25:32,680 --> 01:25:34,760 SHOULD WE BE TESTING. 2126 01:25:34,760 --> 01:25:39,480 IT IS GREAT WE CAN TAKE LOVELY 2127 01:25:39,480 --> 01:25:41,320 PICTURES LOOKING AT RIGHT OR 2128 01:25:41,320 --> 01:25:46,680 LEFT SIDE, UPPER OR LOWER 2129 01:25:46,680 --> 01:25:48,200 LIMB, ANTIGRAPHY MUSCLES, LEFT 2130 01:25:48,200 --> 01:25:51,480 OR RIGHT, HO DO WE KNOW ONE 2131 01:25:51,480 --> 01:25:53,080 MUSCLE REPRESENTS THE OVERALL 2132 01:25:53,080 --> 01:25:53,960 MUSCLE STRENGTH FOR EVERY 2133 01:25:53,960 --> 01:25:57,080 PARTICULAR TASK WE WANT TO USE 2134 01:25:57,080 --> 01:25:58,320 THAT MUSCLE FOR? 2135 01:25:58,320 --> 01:26:01,040 HOW DO WE ATTACH THE RESULTS 2136 01:26:01,040 --> 01:26:03,760 AND BY THAT I MEAN WHAT IS 2137 01:26:03,760 --> 01:26:05,880 MEANINGFUL FOR THE PATIENT. 2138 01:26:05,880 --> 01:26:08,520 MEASURING WHAT WE THINK WE'RE 2139 01:26:08,520 --> 01:26:11,400 MEASURING AND DO WE EVEN KNOW 2140 01:26:11,400 --> 01:26:15,040 WHAT THAT MEASUREMENT MEANS? 2141 01:26:15,040 --> 01:26:16,680 DO WE REALLY UNDERSTAND WHAT 2142 01:26:16,680 --> 01:26:20,520 THAT MEASURE TELLS US AND WHAT 2143 01:26:20,520 --> 01:26:25,640 THAT MEANS AND WHAT TO DO WITH 2144 01:26:25,640 --> 01:26:26,200 IT. 2145 01:26:26,200 --> 01:26:30,240 HOW MUCH ARE WE MEASURING 2146 01:26:30,240 --> 01:26:34,840 DEFICITS ACQUIRED IN THE ICU? 2147 01:26:34,840 --> 01:26:37,560 WE DON'T OFTEN HAVE A BASELINE 2148 01:26:37,560 --> 01:26:40,440 SO HOW DO WE KNOW WHAT NEW 2149 01:26:40,440 --> 01:26:43,720 DEFICITS ARE ACQUIRED IN THE 2150 01:26:43,720 --> 01:26:44,080 ICU? 2151 01:26:44,080 --> 01:26:47,120 AND DO EACH OF THE 2152 01:26:47,120 --> 01:26:48,200 MEASUREMENTS CORRELATE WITH 2153 01:26:48,200 --> 01:26:49,440 THE OTHERS? 2154 01:26:49,440 --> 01:26:53,760 IF WE SAY THEY HAVE LOST 2155 01:26:53,760 --> 01:26:57,200 20 PERCENT AS A FINDING, DO WE 2156 01:26:57,200 --> 01:27:02,320 KNOW HOW THAT TRANSLATES TO 2157 01:27:02,320 --> 01:27:05,520 MUSCLE LOSS AND IS IT 2158 01:27:05,520 --> 01:27:06,800 GENERALIZABLE ACROSS PATIENTS. 2159 01:27:06,800 --> 01:27:07,760 NEXT SLIDE, PLEASE. 2160 01:27:07,760 --> 01:27:11,920 SO THE ANSWER IS TO MEASURE 2161 01:27:11,920 --> 01:27:14,280 MUSCLE BETTER, NEXT SLIDE, 2162 01:27:14,280 --> 01:27:14,600 PLEASE. 2163 01:27:14,600 --> 01:27:19,720 AND CURRENTLY THE ANSWER IS 2164 01:27:19,720 --> 01:27:20,720 NO. 2165 01:27:20,720 --> 01:27:24,760 IT IS NICE TO HAVE MUSH 2166 01:27:24,760 --> 01:27:25,880 FUNCTIONING BUT NOT ALWAYS 2167 01:27:25,880 --> 01:27:28,800 HELPFUL AND WHY IS THAT? 2168 01:27:28,800 --> 01:27:32,000 BECAUSE PATIENTS DON'T 2169 01:27:32,000 --> 01:27:32,720 PRIORITIZE MUSCLE STRENGTH. 2170 01:27:32,720 --> 01:27:34,880 THIS COMES FROM A CONSENSUS 2171 01:27:34,880 --> 01:27:36,480 PROCESS ASKING PATIENTS TO 2172 01:27:36,480 --> 01:27:39,240 RATE OUTCOMES OF IMPORTANT IN 2173 01:27:39,240 --> 01:27:41,520 RELATION TO PHYSICAL REHAB AND 2174 01:27:41,520 --> 01:27:44,440 74 PERCENT OF THEM RATED 2175 01:27:44,440 --> 01:27:46,400 MUSCLE FUNCTION VERSUS 2176 01:27:46,400 --> 01:27:47,200 100 PERCENT RATED PHYSICAL 2177 01:27:47,200 --> 01:27:49,720 FUNCTIONS AS IMPORTANT AND 2178 01:27:49,720 --> 01:27:50,080 WHY? 2179 01:27:50,080 --> 01:27:51,800 BECAUSE MUSCLE FUNCTION ON ITS 2180 01:27:51,800 --> 01:27:54,320 OWN IS NOT MEANINGFUL AND 2181 01:27:54,320 --> 01:27:55,600 DOESN'T TRANSLATE INTO A 2182 01:27:55,600 --> 01:28:00,280 PATIENT ABLE TO DO SOMETHING 2183 01:28:00,280 --> 01:28:03,720 ON HIS OWN. 2184 01:28:03,720 --> 01:28:06,520 AND MUSCLE FUNCTION DOES NOT 2185 01:28:06,520 --> 01:28:07,800 EQUAL PHYSICAL FUNCTION 2186 01:28:07,800 --> 01:28:12,760 BECAUSE THERE ARE MANY OTHER 2187 01:28:12,760 --> 01:28:14,480 THINGS THAT ARE REQUIRED 2188 01:28:14,480 --> 01:28:16,680 BESIDES MUSCLE FUNCTION, 2189 01:28:16,680 --> 01:28:17,320 BALANCE, MOTIVATION, 2190 01:28:17,320 --> 01:28:19,280 COORDINATION, SOME OF THE 2191 01:28:19,280 --> 01:28:20,800 THINGS WE SOMETIMES CAPTURE 2192 01:28:20,800 --> 01:28:23,120 BUT NOT ALWAYS AND ALSO IT 2193 01:28:23,120 --> 01:28:25,200 MODIFIES THEIR ADAPTATION TO 2194 01:28:25,200 --> 01:28:26,200 THE PATIENT STATUS. 2195 01:28:26,200 --> 01:28:30,800 THE PATIENT IS NATURALLY 2196 01:28:30,800 --> 01:28:36,680 CLIMATIZING AND SO WE NEED 2197 01:28:36,680 --> 01:28:40,720 SUPPORT PATIENTS WITH 2198 01:28:40,720 --> 01:28:43,560 ASSISTIVE DEVICES SO THEY CAN 2199 01:28:43,560 --> 01:28:44,720 FUNCTION. 2200 01:28:44,720 --> 01:28:46,000 AND INCREASING EQUITY IN 2201 01:28:46,000 --> 01:28:48,160 ACCESSIBILITY OF THE 2202 01:28:48,160 --> 01:28:48,960 ENVIRONMENT. 2203 01:28:48,960 --> 01:28:50,000 AND ALSO REPRIORITIZATION OF 2204 01:28:50,000 --> 01:28:51,160 PATIENT VALUES IN TERMS OF 2205 01:28:51,160 --> 01:28:53,400 WHAT IS IMPORTANT TO THEM. 2206 01:28:53,400 --> 01:29:03,800 NEXT SLIDE, PLEASE. 2207 01:29:04,640 --> 01:29:05,560 SO. 2208 01:29:05,560 --> 01:29:08,080 SO WHAT WE DON'T KNOW, ONE 2209 01:29:08,080 --> 01:29:10,400 MEASURE TO TRACK RECOVERY ON 2210 01:29:10,400 --> 01:29:11,760 THE CONTINUUM AND IF WE THINK 2211 01:29:11,760 --> 01:29:14,720 IT IS IMPORTANT TO HAVE SOME 2212 01:29:14,720 --> 01:29:16,560 MUSCLE FUNCTION BUT IF WE 2213 01:29:16,560 --> 01:29:18,720 RECOGNIZE IT ISN'T THE ONLY 2214 01:29:18,720 --> 01:29:20,920 CONSTRUCT TO PHYSICAL PUCKS, 2215 01:29:20,920 --> 01:29:25,320 WE NEED A PHYSICAL FUNCTION 2216 01:29:25,320 --> 01:29:27,000 MEASURE TO CAPTURE THAT. 2217 01:29:27,000 --> 01:29:28,440 NEXT SLIDE, PLEASE. 2218 01:29:28,440 --> 01:29:31,120 SO LET'S CHECK IN TO SEE ARE 2219 01:29:31,120 --> 01:29:33,120 WE MEASURING PHYSICAL FUNCTION 2220 01:29:33,120 --> 01:29:33,720 RIGHT? 2221 01:29:33,720 --> 01:29:39,200 BECAUSE WE HAVE OBJECTIVE AND 2222 01:29:39,200 --> 01:29:40,080 SUBJECTIVE MEASURES, THINGS WE 2223 01:29:40,080 --> 01:29:41,920 HEAR FROM THE PATIENTS 2224 01:29:41,920 --> 01:29:43,560 THEMSELVES AS IMPORTANT BUT DO 2225 01:29:43,560 --> 01:29:46,120 WE REALLY FOCUS ON INDIVIDUAL 2226 01:29:46,120 --> 01:29:47,200 PATIENT LEVELS? 2227 01:29:47,200 --> 01:29:49,120 THEIR PHYSICAL ENVIRONMENT, 2228 01:29:49,120 --> 01:29:52,440 THEIR SOCIAL ROLES, INTRINSIC 2229 01:29:52,440 --> 01:29:53,240 MOTIVATORS, PERSONAL 2230 01:29:53,240 --> 01:29:53,960 CIRCUMSTANCES, WHAT RESOURCES 2231 01:29:53,960 --> 01:29:55,960 DO THEY HAVE AND WHAT DOES 2232 01:29:55,960 --> 01:29:59,160 GOOD LOOK LIKE IN THE OUTCOME 2233 01:29:59,160 --> 01:30:00,800 OF THESE PATIENTS. 2234 01:30:00,800 --> 01:30:02,400 WE FOE WHAT IS GOOD BUT IS 2235 01:30:02,400 --> 01:30:04,880 THAT THE SAME FOR THE PATIENT? 2236 01:30:04,880 --> 01:30:05,800 NEXT SLIDE, PLEASE. 2237 01:30:05,800 --> 01:30:06,920 SO WHAT TO DO NEXT? 2238 01:30:06,920 --> 01:30:09,560 I THINK THERE IS A MAJOR GAP 2239 01:30:09,560 --> 01:30:10,840 IN UNDERSTANDING OR THINKING 2240 01:30:10,840 --> 01:30:14,800 AROUND HOW TO DESIGN THE RIGHT 2241 01:30:14,800 --> 01:30:16,880 MEASURE AND WHAT DEGREE IN ANY 2242 01:30:16,880 --> 01:30:19,080 ONE OF THOSE MEASURES OF 2243 01:30:19,080 --> 01:30:21,800 MUSCLE FUNCTION CORRESPONDS TO 2244 01:30:21,800 --> 01:30:23,720 A CHANGE AND HOW MUCH IF 2245 01:30:23,720 --> 01:30:24,240 PHYSICAL FUNCTION. 2246 01:30:24,240 --> 01:30:25,960 WHAT DEGREE OF CHANGE IN 2247 01:30:25,960 --> 01:30:27,920 PHYSICAL FUNCTION IS 2248 01:30:27,920 --> 01:30:30,080 CLINICALLY AND PERSONALLY 2249 01:30:30,080 --> 01:30:33,280 MEANINGFUL FOR AN INDIVIDUAL 2250 01:30:33,280 --> 01:30:33,840 PATIENT? 2251 01:30:33,840 --> 01:30:37,080 AND THAT COULD BE DIFFERENT 2252 01:30:37,080 --> 01:30:39,680 FROM PATIENT TO PATIENT. 2253 01:30:39,680 --> 01:30:41,400 AND WHAT PHYSICAL FUNCTION 2254 01:30:41,400 --> 01:30:44,040 TASK TO MEASURE, CAN THIS BE 2255 01:30:44,040 --> 01:30:45,200 DIFFERENT FOR DIFFERENT 2256 01:30:45,200 --> 01:30:47,040 PATIENTS WITHIN ONE MEASURE. 2257 01:30:47,040 --> 01:30:50,080 ABILITY TO CAPTURE OTHER 2258 01:30:50,080 --> 01:30:50,480 DOMAINS. 2259 01:30:50,480 --> 01:30:54,400 NEXT SLIDE, PLEASE. 2260 01:30:54,400 --> 01:30:57,600 AND THEN FINALLY A STUDY FOR 2261 01:30:57,600 --> 01:30:59,680 THE FUTURE WHICH WE'RE VERY 2262 01:30:59,680 --> 01:31:01,400 GRATEFUL FOR AND WHAT I WOULD 2263 01:31:01,400 --> 01:31:03,120 SUGGEST WE LOOK AT. 2264 01:31:03,120 --> 01:31:06,440 THIS HAS COME IN THE LAST 2265 01:31:06,440 --> 01:31:13,240 FIVE, TEN YEARS OR SO, WHERE 2266 01:31:13,240 --> 01:31:15,560 WE CAN VIEDIZE THE THRESHOLDS 2267 01:31:15,560 --> 01:31:18,640 FOR EACH PATIENT IN TERMS OF 2268 01:31:18,640 --> 01:31:19,600 CONTROL, INTERVENTION AND 2269 01:31:19,600 --> 01:31:20,120 OUTCOMES. 2270 01:31:20,120 --> 01:31:29,640 I AM NOT SURE WE HAVE MUCH FOR 2271 01:31:29,640 --> 01:31:35,920 A TRIAL ON THE PATIENT TO 2272 01:31:35,920 --> 01:31:37,520 ASSESS BUT LET'S USE THAT AS 2273 01:31:37,520 --> 01:31:43,760 WHETHER THEY HAVE A POSITIVE 2274 01:31:43,760 --> 01:31:44,520 CHANGE IN CONTRIBUTION. 2275 01:31:44,520 --> 01:31:52,560 SO THAT CHANGE IS DETERMINED 2276 01:31:52,560 --> 01:31:54,600 BY THEIR PERSONAL VALUES, 2277 01:31:54,600 --> 01:31:56,480 SOCIAL ROLES AND PHYSICAL 2278 01:31:56,480 --> 01:31:57,360 ENVIRONMENT. 2279 01:31:57,360 --> 01:32:00,960 SO WE MOVE THAT TO MEASURES 2280 01:32:00,960 --> 01:32:04,120 WHERE THEY HAVE AN ADJUSTED 2281 01:32:04,120 --> 01:32:05,120 DIFFERENCE SO THANK YOU VERY 2282 01:32:05,120 --> 01:32:07,200 MUCH FOR YOUR TIME. 2283 01:32:07,200 --> 01:32:10,760 >>THANK YOU DO CONNOLLY, THAT 2284 01:32:10,760 --> 01:32:12,760 WAS A FANTASTIC TALK AND ALSO 2285 01:32:12,760 --> 01:32:14,120 RESULTED IN A LOT OF 2286 01:32:14,120 --> 01:32:14,840 DISCUSSION AND QUESTIONS IN 2287 01:32:14,840 --> 01:32:17,040 THE CHAT SO THANK YOU SO MUCH 2288 01:32:17,040 --> 01:32:19,880 FOR GETTING US STARTED ON THE 2289 01:32:19,880 --> 01:32:20,680 MEASUREMENT FOCUS OF EACH 2290 01:32:20,680 --> 01:32:22,320 SESSION AND I WOULD LIKE TO 2291 01:32:22,320 --> 01:32:23,920 START WITH ONE QUESTION -- 2292 01:32:23,920 --> 01:32:24,960 ACTUALLY THERE ARE SEVERAL BUT 2293 01:32:24,960 --> 01:32:26,800 I WILL START WITH ONE QUESTION 2294 01:32:26,800 --> 01:32:28,480 FROM THE CHAT WHICH ACTUALLY 2295 01:32:28,480 --> 01:32:39,000 CAME FROM MY COMODERATOR, 2296 01:32:46,360 --> 01:32:46,680 Dr. IWASHYNA. 2297 01:32:46,680 --> 01:32:51,160 AT THE PRESENT TIME 2298 01:32:51,160 --> 01:32:55,720 SHOW'MUSCLE LOSS AND THE 2299 01:32:55,720 --> 01:32:56,640 MODERATION ACROSS GROUPS. 2300 01:32:56,640 --> 01:32:57,200 >> GREAT QUESTION. 2301 01:32:57,200 --> 01:32:59,240 I THINK WE HAVE FOCUSED ON 2302 01:32:59,240 --> 01:33:01,560 MUSCLES THAT ARE EASY TO GET 2303 01:33:01,560 --> 01:33:04,080 TO AND EASY TO MEASURE AND 2304 01:33:04,080 --> 01:33:06,720 THEY ARE NORMALLY LARGE 2305 01:33:06,720 --> 01:33:08,640 DEFINED MUSCLES TO BEGIN WITH 2306 01:33:08,640 --> 01:33:11,720 SO WHEN WE WERE STARTING TO 2307 01:33:11,720 --> 01:33:13,640 GET EXCITED TO TAKE PICTURES 2308 01:33:13,640 --> 01:33:16,440 OF MUSCLES, THEY WERE EASY TO 2309 01:33:16,440 --> 01:33:21,520 GET TO AND EASY TO TAKE 2310 01:33:21,520 --> 01:33:23,040 PICTURES OF. 2311 01:33:23,040 --> 01:33:25,840 I DON'T THINK WE SEE ALL OF 2312 01:33:25,840 --> 01:33:27,880 THE SAME MUSCLE TYPES IN THE 2313 01:33:27,880 --> 01:33:28,720 SAME PATIENTS AS WELL AND 2314 01:33:28,720 --> 01:33:31,120 THERE WILL BE HUGE VARIABILITY 2315 01:33:31,120 --> 01:33:35,880 IN ONE PATIENT AND ACROSS 2316 01:33:35,880 --> 01:33:38,640 MULTIPLES OF PATIENTS SO WE 2317 01:33:38,640 --> 01:33:40,720 REALLY NEED A CONTROL WHERE WE 2318 01:33:40,720 --> 01:33:42,320 CONTROL THE MEASURES AND THAT 2319 01:33:42,320 --> 01:33:49,360 CAN BE GREAT AT COMPARING. 2320 01:33:49,360 --> 01:33:50,480 COMPARING PATIENTS IN THE BET 2321 01:33:50,480 --> 01:33:52,800 NEXT TO EACH OTHER IS REALLY 2322 01:33:52,800 --> 01:33:54,040 DIFFICULT BECAUSE THEY DON'T 2323 01:33:54,040 --> 01:33:55,440 KNOW WHAT THAT MEANS IN TERMS 2324 01:33:55,440 --> 01:33:59,720 OF WHAT THEY CAN DO 2325 01:33:59,720 --> 01:34:00,120 AFTERWARDS. 2326 01:34:00,120 --> 01:34:01,560 WE SEE PATIENTS WHO SIT UP ON 2327 01:34:01,560 --> 01:34:05,440 THE SIDE OF THE BED AND OTHERS 2328 01:34:05,440 --> 01:34:09,880 HAVE THE LOOKED AND LOADED 2329 01:34:09,880 --> 01:34:13,640 MUSCLES WHO SURPRISE US IN 2330 01:34:13,640 --> 01:34:16,240 ENGAGING IN THERAPY AND OTHER 2331 01:34:16,240 --> 01:34:16,640 UTILIZATION. 2332 01:34:16,640 --> 01:34:20,680 SO IT IS ONE OF THE CAVEATS TO 2333 01:34:20,680 --> 01:34:22,560 THE MEASURES, IT IS HELPFUL IN 2334 01:34:22,560 --> 01:34:24,600 THAT IT ALLOWS US TO EXAMINE 2335 01:34:24,600 --> 01:34:27,160 MUSCLES A LITTLE MORE BUT 2336 01:34:27,160 --> 01:34:28,680 DOESN'T NECESSARILY MEAN ONE 2337 01:34:28,680 --> 01:34:30,280 MUSCLE REFLECTS ALL THE 2338 01:34:30,280 --> 01:34:30,800 OTHERS. 2339 01:34:30,800 --> 01:34:33,480 >>THANKS, AND THEN THAT ALSO 2340 01:34:33,480 --> 01:34:35,360 RAISES AN IMPORTANT POINT 2341 01:34:35,360 --> 01:34:37,920 WHICH TE RRI BROUGHT UP IN THE 2342 01:34:37,920 --> 01:34:39,840 CHAT, THOSE ARE THE MOST 2343 01:34:39,840 --> 01:34:41,760 MUSCLE MASS MAY LOSE THE MOST 2344 01:34:41,760 --> 01:34:43,360 BUT ALSO HAVE THE GREATEST 2345 01:34:43,360 --> 01:34:46,280 POTENTIAL FOR RETURN TO 2346 01:34:46,280 --> 01:34:49,320 BASELINE AND RECOVERY. 2347 01:34:49,320 --> 01:34:51,760 >>AND SO IT SORT OF DEPENDS 2348 01:34:51,760 --> 01:34:56,240 ON WHAT PATIENTS COME IN WITH. 2349 01:34:56,240 --> 01:34:58,040 BUT ALSO PATIENTS WHO HAVE 2350 01:34:58,040 --> 01:35:00,520 CHRONIC DISEASE HAVE ALSO 2351 01:35:00,520 --> 01:35:03,280 ADAPTED TO NOT HAVING 2352 01:35:03,280 --> 01:35:04,000 COMPLETELY FUNCTIONAL MUSCLES 2353 01:35:04,000 --> 01:35:06,600 FOR LACK OF A BETTER TERM SO 2354 01:35:06,600 --> 01:35:08,720 THEY CAN REPORT DIFFERENTLY 2355 01:35:08,720 --> 01:35:11,440 BECAUSE THEY HAVE CLIMATIZED 2356 01:35:11,440 --> 01:35:11,840 AND ADAPTED. 2357 01:35:11,840 --> 01:35:13,080 >> AND THEN I ACTUALLY -- 2358 01:35:13,080 --> 01:35:15,000 THAT IS A GREAT SEGUE INTO A 2359 01:35:15,000 --> 01:35:16,720 QUESTION I HAD FOR YOU WHICH I 2360 01:35:16,720 --> 01:35:22,920 THINK WE WILL END UP TALKING 2361 01:35:22,920 --> 01:35:26,440 AGAIN DURING THE PANEL 2362 01:35:26,440 --> 01:35:29,160 DISCUSSION BUT IN IN OUR WORK 2363 01:35:29,160 --> 01:35:33,840 WITH OLDER ICU SURVIVORS, WE 2364 01:35:33,840 --> 01:35:37,160 FOCUS ON ACTIVITY BECAUSE 2365 01:35:37,160 --> 01:35:38,400 GERIATRIC STUDIES HAVE SHOWN 2366 01:35:38,400 --> 01:35:44,240 FOR MANY YEARS THAT OLDER 2367 01:35:44,240 --> 01:35:46,440 PATIENTS VALUE FUNCTION AS A 2368 01:35:46,440 --> 01:35:48,280 PRIORITY AND SEEMS LIKE THAT 2369 01:35:48,280 --> 01:35:51,160 IS BEING SEEN IN PATIENTS ALL 2370 01:35:51,160 --> 01:35:51,800 AGES. 2371 01:35:51,800 --> 01:35:54,720 SO ARE YOU SUGGESTING WE 2372 01:35:54,720 --> 01:35:56,920 SHOULD BE SUGGESTING SERIAL 2373 01:35:56,920 --> 01:35:58,080 MEASURES AND FUNCTIONAL 2374 01:35:58,080 --> 01:36:00,400 ACTIVITIES ALONG WITH MEASURES 2375 01:36:00,400 --> 01:36:00,960 IN MUSCLE STRENGTH? 2376 01:36:00,960 --> 01:36:02,440 I DON'T WANT TO HAVE YOU JUMP 2377 01:36:02,440 --> 01:36:04,640 AHEAD BUT KIND OF WHAT I WAS 2378 01:36:04,640 --> 01:36:06,160 GATHERING FROM YOUR SLIDES. 2379 01:36:06,160 --> 01:36:07,200 >>NO, I THINK YOU ARE RIGHT 2380 01:36:07,200 --> 01:36:09,400 AND I THINK WHAT THAT MEASURE 2381 01:36:09,400 --> 01:36:11,400 IS WILL BE DIFFERENT FOR 2382 01:36:11,400 --> 01:36:12,680 DIFFERENT PATIENTS ACCORDING 2383 01:36:12,680 --> 01:36:15,960 TO AGE, WHAT THEIR PERSONAL 2384 01:36:15,960 --> 01:36:18,240 INTERESTS OR PERSONAL STATUS 2385 01:36:18,240 --> 01:36:19,720 IS SO ABSOLUTELY AND I THINK 2386 01:36:19,720 --> 01:36:22,280 THOSE ARE THE KIND OF THINGS 2387 01:36:22,280 --> 01:36:23,680 THAT MATCH TO PATIENTS AND 2388 01:36:23,680 --> 01:36:26,840 REGARDLESS OF YOUR AGE, YOU 2389 01:36:26,840 --> 01:36:29,760 STILL WANT TO BE INDEPENDENT. 2390 01:36:29,760 --> 01:36:32,400 WHAT YOUR PAST WAS WITH OTHER 2391 01:36:32,400 --> 01:36:33,360 PATIENTS, YOU MAY DIFFER BUT 2392 01:36:33,360 --> 01:36:37,760 YOU WANT TO GET BACK TO WORK 2393 01:36:37,760 --> 01:36:40,040 OR SIMPLY THE GARDEN OR JUST 2394 01:36:40,040 --> 01:36:42,680 TO GET AROUND AND BE 2395 01:36:42,680 --> 01:36:44,200 INDEPENDENT, THAT MAY VARY BUT 2396 01:36:44,200 --> 01:36:46,480 BEING ABLE TO MATCH THAT TO 2397 01:36:46,480 --> 01:36:48,480 THE PATIENTS AND INTERVENTION 2398 01:36:48,480 --> 01:36:51,040 FOR THAT IS IMPORTANT 2399 01:36:51,040 --> 01:36:51,440 ABSOLUTELY. 2400 01:36:51,440 --> 01:36:52,320 >>ABSOLUTELY AND WE WANT TO 2401 01:36:52,320 --> 01:36:56,880 MAKE SURE WE COME BACK TO THE 2402 01:36:56,880 --> 01:36:59,120 POINT ABOUT ADAPTATION DURING 2403 01:36:59,120 --> 01:37:01,520 THE PANEL DISCUSSION BECAUSE 2404 01:37:01,520 --> 01:37:09,880 ULTIMATELY PATIENTS ADAPT TO 2405 01:37:09,880 --> 01:37:12,000 OUTCOMES AND THAT DIFFERS WITH 2406 01:37:12,000 --> 01:37:12,960 EQUIPMENT VERSUS AT HOME. 2407 01:37:12,960 --> 01:37:15,400 SO THANK YOU SO MUCH, THAT WAS 2408 01:37:15,400 --> 01:37:15,800 FANTASTIC. 2409 01:37:15,800 --> 01:37:18,280 I AM NOW GOING TO INTRODUCE 2410 01:37:18,280 --> 01:37:25,840 OUR LAST SPEAKER IN SECTION 1, 2411 01:37:25,840 --> 01:37:28,680 Dr. JASON FA LVEY, ASSISTANT 2412 01:37:28,680 --> 01:37:30,960 PROFESSOR IN THE DEPARTMENT OF 2413 01:37:30,960 --> 01:37:32,680 PHYSICAL THERAPY AND 2414 01:37:32,680 --> 01:37:33,360 REHABILITATION STKAOEUPBZ AND 2415 01:37:33,360 --> 01:37:34,320 DEPARTMENT OF 'EM DEEM I DON'T 2416 01:37:34,320 --> 01:37:37,040 GO AND PUBLIC HEALTH TESTIFY 2417 01:37:37,040 --> 01:37:38,520 UNIVERSITY OF MARYLAND SCHOOL 2418 01:37:38,520 --> 01:37:39,800 OF MEDICINE. 2419 01:37:39,800 --> 01:37:42,200 HE HAS DEVOTED HIS YEAR TO 2420 01:37:42,200 --> 01:37:44,640 INCLUDE HIGH QUALITY AGING IN 2421 01:37:44,640 --> 01:37:48,480 PLACE FOR OLDER ADULTS 2422 01:37:48,480 --> 01:37:50,640 RECOVERING FROM ILLNESS AND 2423 01:37:50,640 --> 01:37:51,200 INJURIES. 2424 01:37:51,200 --> 01:37:53,760 HE IS THE SECOND EVER PHYSICAL 2425 01:37:53,760 --> 01:37:56,920 THERAPIST TO BE FUNDED BY 2426 01:37:56,920 --> 01:37:57,760 EMERGING LEADERS CAREER 2427 01:37:57,760 --> 01:38:00,120 DEVELOPMENT FROM THE NIA AND 2428 01:38:00,120 --> 01:38:03,000 ALSO SUPPORTED BY RESEARCH 2429 01:38:03,000 --> 01:38:04,840 GRANTS FROM NHLBI AND I AM 2430 01:38:04,840 --> 01:38:09,960 PROUD TO SAY HE IS A FORMER 2431 01:38:09,960 --> 01:38:11,840 MENTEE OF MINE AND DELIGHTED 2432 01:38:11,840 --> 01:38:15,040 HE IS SPEAKING IN THIS SESSION 2433 01:38:15,040 --> 01:38:18,720 SO THANK YOU FOR BEING HERE, 2434 01:38:18,720 --> 01:38:22,720 CAPTAIN WAIT TO HEAR FROM YOU. 2435 01:38:22,720 --> 01:38:25,600 >>HUMBLED BY THE INTRODUCTION 2436 01:38:25,600 --> 01:38:27,120 AND THANK Dr. JACKSON FOR 2437 01:38:27,120 --> 01:38:28,840 STARTING US OFF WITH THAT 2438 01:38:28,840 --> 01:38:30,120 WONDERFUL TIE. 2439 01:38:30,120 --> 01:38:31,160 REALLY EXCITED TO TALK ABOUT 2440 01:38:31,160 --> 01:38:33,120 THE SO MANY DETERMINANTS OF 2441 01:38:33,120 --> 01:38:36,560 HEALTH AND HOW THAT INFLUENCES 2442 01:38:36,560 --> 01:38:38,360 RORY FROM ACUTE RESPIRATORY 2443 01:38:38,360 --> 01:38:38,880 DISTRESS SYNDROME. 2444 01:38:38,880 --> 01:38:40,360 I THINK IT TIES IN WITH SO 2445 01:38:40,360 --> 01:38:41,960 MANY OF THE THINGS YOU HAVE 2446 01:38:41,960 --> 01:38:43,480 HEARD FROM THE SPEAKERS AND I 2447 01:38:43,480 --> 01:38:45,520 HOPE I HAVE DO JUSTICE IN 2448 01:38:45,520 --> 01:38:47,760 PULLING THESE THINGS TOGETHER. 2449 01:38:47,760 --> 01:38:51,040 NEXT SLIDE. 2450 01:38:51,040 --> 01:38:54,560 DISCLOSURES IN FUNDING, NONE 2451 01:38:54,560 --> 01:38:56,080 PARTICULARLY RELEVANT IN THIS 2452 01:38:56,080 --> 01:38:56,400 TALK. 2453 01:38:56,400 --> 01:38:59,760 MY HAIR LOS IS NOT CAUSED BY 2454 01:38:59,760 --> 01:39:02,040 CRITICAL ILLNESS BUT IS 2455 01:39:02,040 --> 01:39:02,480 INTENTIONAL. 2456 01:39:02,480 --> 01:39:03,600 NEXT SLIDE, PLEASE. 2457 01:39:03,600 --> 01:39:05,120 LET'S TALK ABOUT SOCIAL 2458 01:39:05,120 --> 01:39:06,240 DETERMINANTS OF HEALTH AND 2459 01:39:06,240 --> 01:39:08,120 WHAT WE REALLY MEAN IS WE ARE 2460 01:39:08,120 --> 01:39:10,760 ALL TALKING ABOUT THE SAME 2461 01:39:10,760 --> 01:39:13,040 LANGUAGE. 2462 01:39:13,040 --> 01:39:16,640 THIS GRAPHIC FROM THE 2030 2463 01:39:16,640 --> 01:39:19,400 INITIATIVE, I WANT TO POINT 2464 01:39:19,400 --> 01:39:21,240 OUT EDUCATIONAL ACCESS AND 2465 01:39:21,240 --> 01:39:21,960 QUALITY TRANSLATES DIFFERENTLY 2466 01:39:21,960 --> 01:39:23,880 FOR PATIENTS AND WHERE DO WE 2467 01:39:23,880 --> 01:39:24,880 FIND RESOURCES? 2468 01:39:24,880 --> 01:39:26,360 HEALTHCARE ACCESS AND QUALITY 2469 01:39:26,360 --> 01:39:29,440 IS HUGELY IMPORTANT AND Dr. 2470 01:39:29,440 --> 01:39:31,160 SEVIN POINTED THIS OUT EARLIER 2471 01:39:31,160 --> 01:39:33,680 IN TERMS OF HOW DO WE GET 2472 01:39:33,680 --> 01:39:36,080 PATIENTS INTO THESE CLINICS. 2473 01:39:36,080 --> 01:39:37,120 YOUR NEIGHBORHOOD BUILT 2474 01:39:37,120 --> 01:39:38,440 ENVIRONMENT WHICH WE HAVEN'T 2475 01:39:38,440 --> 01:39:40,080 HEARD A LOT ABOUT AND I WILL 2476 01:39:40,080 --> 01:39:41,840 SHARE MORE INFORMATION IN THAT 2477 01:39:41,840 --> 01:39:43,760 CONTEXT ON HOW THAT WILL 2478 01:39:43,760 --> 01:39:47,600 INFLUENCE YOUR RECOVERY AND 2479 01:39:47,600 --> 01:39:49,120 MAYBE INTERSECT MAKING THEM 2480 01:39:49,120 --> 01:39:51,600 LESS EFFECTIVE IF WE DON'T 2481 01:39:51,600 --> 01:39:55,760 ADDRESS SOME OF THE 2482 01:39:55,760 --> 01:39:56,160 CHALLENGES. 2483 01:39:56,160 --> 01:39:58,200 AND SOCIAL COMMUNITY CONTEXT, 2484 01:39:58,200 --> 01:40:00,360 WE RECOGNIZE THE IMPORTANCE OF 2485 01:40:00,360 --> 01:40:01,720 SOCIAL SUPPORT AND WE HAVE 2486 01:40:01,720 --> 01:40:03,600 MANY PATIENTS WHO WORK WITH 2487 01:40:03,600 --> 01:40:05,040 SURVIVORS IN COMMUNITIES THAT 2488 01:40:05,040 --> 01:40:08,120 REALLY BOOST THEM UP AND HELP 2489 01:40:08,120 --> 01:40:09,640 THEM FIND RESOURCES AND HELP 2490 01:40:09,640 --> 01:40:12,000 SHARE IN THEIR RECOVERY BUT I 2491 01:40:12,000 --> 01:40:13,480 WORK WITH SEVERAL PATIENTS ON 2492 01:40:13,480 --> 01:40:14,920 THE OTHER HAND WHO LIVE IN 2493 01:40:14,920 --> 01:40:18,520 FEAR OF THEIR COMMUNITY AND 2494 01:40:18,520 --> 01:40:20,240 SOCIAL NEIGHBORS, MAYBE FEAR 2495 01:40:20,240 --> 01:40:21,600 OF VIOLENT CRIME FROM PEOPLE 2496 01:40:21,600 --> 01:40:22,640 WHO LIVE IN THEIR 2497 01:40:22,640 --> 01:40:23,400 NEIGHBORHOODS SO THAT IS 2498 01:40:23,400 --> 01:40:24,960 ANOTHER SIDE OF THE COMMUNITY 2499 01:40:24,960 --> 01:40:28,000 CONTEXT TO BE AWARE OF AND HOW 2500 01:40:28,000 --> 01:40:31,960 DO WE HELP PEOPLE NAVIGATE 2501 01:40:31,960 --> 01:40:34,200 THROUGH THE COMMUNITY WITH 2502 01:40:34,200 --> 01:40:36,280 HIGH CRIME AREAS AND THE 2503 01:40:36,280 --> 01:40:42,560 ANSWER IS MORE EXERCISE. 2504 01:40:42,560 --> 01:40:45,640 ECONOMYING STABILITY IS 2505 01:40:45,640 --> 01:40:52,120 SOMETHING WE TALK A LOT IF 2506 01:40:52,120 --> 01:40:53,720 WITH CRITICAL ILLNESS. 2507 01:40:53,720 --> 01:40:56,760 SO I WILL BRING UP THE 2508 01:40:56,760 --> 01:40:59,600 NEIGHBORHOOD LEVEL RISK 2509 01:40:59,600 --> 01:41:01,520 FACTORS INFLUENCING DISABILITY 2510 01:41:01,520 --> 01:41:02,720 DEVELOPMENT AND RECOVERY. 2511 01:41:02,720 --> 01:41:07,160 WE KNOW IT NEEDS SOCIAL 2512 01:41:07,160 --> 01:41:09,440 SUPPORT BUT ALSO NEEDS 2513 01:41:09,440 --> 01:41:11,360 INTERVENTIONS TO BE HELPFUL. 2514 01:41:11,360 --> 01:41:13,040 NEXT SLIDE, PLEASE. 2515 01:41:13,040 --> 01:41:17,480 SO LET'S TELL A TALE OF TWO 2516 01:41:17,480 --> 01:41:18,440 RECOVERIES. 2517 01:41:18,440 --> 01:41:22,160 JIM, HOSPITALIZED FOR 17 DAYS, 2518 01:41:22,160 --> 01:41:29,360 MECHANICALLY VENTILATED, HAS 2519 01:41:29,360 --> 01:41:30,600 DELIRIUM, SIGNIFICANT 2520 01:41:30,600 --> 01:41:32,200 ICU-ACQUIRED WEAKNESS, MAY 2521 01:41:32,200 --> 01:41:35,680 HAVE MORE THAN 20 PERCENT 2522 01:41:35,680 --> 01:41:37,280 WHICH Dr. CONNOLLY WAS 2523 01:41:37,280 --> 01:41:38,760 MENTIONING AND MAYBE WAS FRAIL 2524 01:41:38,760 --> 01:41:41,200 WHICH IS A CERTAIN RISK 2525 01:41:41,200 --> 01:41:41,560 FACTOR. 2526 01:41:41,560 --> 01:41:43,480 BUT THEN THERE WAS MARVIN WITH 2527 01:41:43,480 --> 01:41:45,560 THE SAME LEVEL OF 2528 01:41:45,560 --> 01:41:46,480 HOSPITALIZATION, TWO PATIENTS 2529 01:41:46,480 --> 01:41:50,880 IDENTICAL IN TERMS OF THEIR 2530 01:41:50,880 --> 01:41:51,920 MEDICAL INFORMATION. 2531 01:41:51,920 --> 01:41:53,720 NEXT SLIDE. 2532 01:41:53,720 --> 01:41:57,360 SAY JIM LIVES IN CENTRAL PARK, 2533 01:41:57,360 --> 01:41:59,080 A SUPPORTIVE SPOUSE AND 2534 01:41:59,080 --> 01:42:02,320 SEVERAL PAID CAREGIVERS AND 2535 01:42:02,320 --> 01:42:04,240 FINANCIALLY WEALTHY TO PAY FOR 2536 01:42:04,240 --> 01:42:09,720 WHATEVER SUPPORTS HE NEEDS, 2537 01:42:09,720 --> 01:42:10,360 TAXIS, FINANCIAL SUPPORT. 2538 01:42:10,360 --> 01:42:11,160 AND GOES TO ONE OF THE 2539 01:42:11,160 --> 01:42:13,640 HOSPITALS IN NEW YORK. 2540 01:42:13,640 --> 01:42:19,840 CONTRAST THAT WITH MARVIN WHO 2541 01:42:19,840 --> 01:42:25,080 LIVES IN RURAL NORTHERN MAINE, 2542 01:42:25,080 --> 01:42:26,960 SOCIALLY ISOLATED AND MEDICAID 2543 01:42:26,960 --> 01:42:32,320 ELIGIBLE, LIVES NEAR A PAPER 2544 01:42:32,320 --> 01:42:35,560 MILL AND WITH THE POLLUTION 2545 01:42:35,560 --> 01:42:36,600 HAS DIFFICULTY BREATHING WHEN 2546 01:42:36,600 --> 01:42:39,120 HE IS OUTSIDE, NEXT SLIDE. 2547 01:42:39,120 --> 01:42:42,080 SO THE IMPLICATIONS OF POOR 2548 01:42:42,080 --> 01:42:43,360 SOCIAL CONNECTEDNESS, THERE IS 2549 01:42:43,360 --> 01:42:46,200 A 29 PERCENT INCREASE IN RISK 2550 01:42:46,200 --> 01:42:48,760 FOR CORONARY HEART DISEASE AND 2551 01:42:48,760 --> 01:42:50,880 INCREASE IN DEVELOPING 2552 01:42:50,880 --> 01:42:53,200 DEMENTIA IN PEOPLE WITH POOR 2553 01:42:53,200 --> 01:42:54,560 SOCIAL NETWORKS AND THESE 2554 01:42:54,560 --> 01:42:57,560 PATIENTS HAVE HIGHER RISK OF 2555 01:42:57,560 --> 01:42:58,920 DEVELOPING ADL DISABILITY OVER 2556 01:42:58,920 --> 01:43:07,720 SIX YEARS SO SOCIAL ISOLATION 2557 01:43:07,720 --> 01:43:12,120 AND LONELINESS IN OLDER 2558 01:43:12,120 --> 01:43:12,440 ADULTS. 2559 01:43:12,440 --> 01:43:16,360 SO HOW DO WE USE MEASURING 2560 01:43:16,360 --> 01:43:18,880 SOCIAL CONNECTIONEDNESS AS A 2561 01:43:18,880 --> 01:43:20,120 DRIVER, NEXT SLIDE, PLEASE. 2562 01:43:20,120 --> 01:43:21,600 WE ARE PRETTY GOOD AT 2563 01:43:21,600 --> 01:43:23,240 CONNECTING WITH FRIENDS AND 2564 01:43:23,240 --> 01:43:23,680 FAMILY. 2565 01:43:23,680 --> 01:43:31,040 WE OFTEN ASK IF PEOPLE HAVE A 2566 01:43:31,040 --> 01:43:32,960 PARTNER, ASK ABOUT FRIENDS OF 2567 01:43:32,960 --> 01:43:34,800 SOCIAL SUPPORT BUT DON'T OFTEN 2568 01:43:34,800 --> 01:43:36,080 ASK ABOUT CONNECTIONS WITH THE 2569 01:43:36,080 --> 01:43:38,880 COMMUNITY AND IF WE DO IT IS 2570 01:43:38,880 --> 01:43:40,000 MORE CONVERSATIONAL AND NOT 2571 01:43:40,000 --> 01:43:40,960 WITH EXECUTION. 2572 01:43:40,960 --> 01:43:41,680 NEXT SLIDE, PLEASE. 2573 01:43:41,680 --> 01:43:43,880 AND THAT MIGHT BE A MISSED 2574 01:43:43,880 --> 01:43:48,840 OPPORTUNITY -- SORRY, NEXT 2575 01:43:48,840 --> 01:43:51,960 SLIDE -- BECAUSE THIS SCORE OF 2576 01:43:51,960 --> 01:43:54,400 0 TO 6, 6 BEING THE MOST EYES 2577 01:43:54,400 --> 01:43:57,600 HATED SO WHEN WE DO THAT, WE 2578 01:43:57,600 --> 01:43:59,240 RECOGNIZE PEOPLE HOSPITALIZED 2579 01:43:59,240 --> 01:44:04,000 IN THE ICU ARE MUCH MORE 2580 01:44:04,000 --> 01:44:05,720 LIKELY TO DIE FOLLOWING THEIR 2581 01:44:05,720 --> 01:44:08,280 ADMISSION, IF WE CAN GO BACK 2582 01:44:08,280 --> 01:44:09,800 TO THAT GRAPH, PLEASE, THANK 2583 01:44:09,800 --> 01:44:10,080 YOU. 2584 01:44:10,080 --> 01:44:11,560 THEY ARE MUCH MORE LIKELY TO 2585 01:44:11,560 --> 01:44:13,600 DIE IF THEY ARE SOCIALLY 2586 01:44:13,600 --> 01:44:14,080 ISOLATED. 2587 01:44:14,080 --> 01:44:16,480 YOU CAN SEE THERE IS ALMOST A 2588 01:44:16,480 --> 01:44:18,120 PRO-FOLD INCREASE IN MORTALITY 2589 01:44:18,120 --> 01:44:19,960 BETWEEN THE MOST SOCIALLY 2590 01:44:19,960 --> 01:44:21,320 INGRADUATED, PEOPLE WITH THE 2591 01:44:21,320 --> 01:44:23,240 MOST SOCIAL SUPPORT, AND 2592 01:44:23,240 --> 01:44:28,400 PEOPLE WHO ARE MOST EYES LAID 2593 01:44:28,400 --> 01:44:32,760 AND -- ISOLATED AND THAT 2594 01:44:32,760 --> 01:44:35,160 DOESN'T JUST RELATE TO 2595 01:44:35,160 --> 01:44:38,320 MORTALITY. 2596 01:44:38,320 --> 01:44:39,440 AS SOCIAL EYESIZATION 2597 01:44:39,440 --> 01:44:42,680 INCREASES, THERE IS A INCREASE 2598 01:44:42,680 --> 01:44:43,920 IN CRITICAL ILLNESS. 2599 01:44:43,920 --> 01:44:45,760 THAT CAN BE THE DIFFERENCE 2600 01:44:45,760 --> 01:44:47,920 BETWEEN SOMEBODY GETTING IN 2601 01:44:47,920 --> 01:44:50,000 AND OUT OF THE SHOWER WHICH IS 2602 01:44:50,000 --> 01:44:53,320 A MAJOR SOURCE OF INDEPENDENCE 2603 01:44:53,320 --> 01:44:56,040 FOR ADULTS AND PROCESS NOT 2604 01:44:56,040 --> 01:45:01,760 TICK OF FUTURE 2605 01:45:01,760 --> 01:45:02,800 INSTITUTIONALIZATION, OTHER 2606 01:45:02,800 --> 01:45:04,600 OUTCOMES FOR OLDER ADULTS. 2607 01:45:04,600 --> 01:45:06,120 NEXT SLIDE, PLEASE. 2608 01:45:06,120 --> 01:45:09,440 BUT THIS IS MODIFIABLE. 2609 01:45:09,440 --> 01:45:20,000 WE KNOW WE CAN AFFECT THOSE BY 2610 01:45:20,560 --> 01:45:22,640 INTERVENING IN COMMUNITY 2611 01:45:22,640 --> 01:45:27,360 STAKEHOLDERS TO ADOPT 2612 01:45:27,360 --> 01:45:28,360 INTERVENTIONS, PEER SUPPORTS, 2613 01:45:28,360 --> 01:45:30,920 HELPING CONNECT PATIENTS WITH 2614 01:45:30,920 --> 01:45:33,800 SOCIAL SERVICES ACROSS THE 2615 01:45:33,800 --> 01:45:35,400 COUNTRY, LIKE TRANSPORTATION, 2616 01:45:35,400 --> 01:45:36,400 SENIOR COMPANION SERVICES LIKE 2617 01:45:36,400 --> 01:45:38,920 ARE OFFERED IN PREDATOR TO 2618 01:45:38,920 --> 01:45:40,080 HELP BRIDGE THESE SOCIAL MEETS 2619 01:45:40,080 --> 01:45:42,600 AND NOT JUST FOR QUALITY OF 2620 01:45:42,600 --> 01:45:44,560 LIFE, TO ALSO HELP THEM 2621 01:45:44,560 --> 01:45:45,960 PARTICIPATE IN RESTORATIVE 2622 01:45:45,960 --> 01:45:47,880 CARE TO IMPROVE PHYSICAL AND 2623 01:45:47,880 --> 01:45:49,200 COGNITIVE FUNCTION. 2624 01:45:49,200 --> 01:45:51,600 NEXT SLIDE, PLEASE. 2625 01:45:51,600 --> 01:45:52,840 BUT ALSO ECONOMIC STABILITY 2626 01:45:52,840 --> 01:45:54,800 GETS IN THE WAY OF SOME OF 2627 01:45:54,800 --> 01:45:57,440 THESE WELL MEANING 2628 01:45:57,440 --> 01:45:58,120 INTERVENTIONS. 2629 01:45:58,120 --> 01:45:59,280 WE DEVELOPED CLINICAL TRIALS 2630 01:45:59,280 --> 01:46:01,000 AND OFTEN FORGET PEOPLE HAVE 2631 01:46:01,000 --> 01:46:04,200 TO WORK TO RETURN THEIR 2632 01:46:04,200 --> 01:46:04,560 INCOME. 2633 01:46:04,560 --> 01:46:09,040 THEY MAY NOT HAVE INSURANCE 2634 01:46:09,040 --> 01:46:10,360 COVERAGE TO FULLY PARTICIPATE 2635 01:46:10,360 --> 01:46:14,240 AND IT COSTS A LOT TO GO TO 2636 01:46:14,240 --> 01:46:15,400 MEDICAL APPOINTMENTS, SOME 2637 01:46:15,400 --> 01:46:17,200 LIMPING IN RURAL ENVIRONMENTS 2638 01:46:17,200 --> 01:46:18,440 HAVE TO TRAVEL SEVERAL HOURS 2639 01:46:18,440 --> 01:46:21,760 TO GET TO YOUR MEDICAL CARE. 2640 01:46:21,760 --> 01:46:25,520 AND EQUIPMENT THAT IS ADAPTIVE 2641 01:46:25,520 --> 01:46:27,320 TO DISABILITY IS OFTEN NOT 2642 01:46:27,320 --> 01:46:30,320 COVERED SO THERE IS A LOT OF 2643 01:46:30,320 --> 01:46:32,240 FINANCIAL COSTS THAT 2644 01:46:32,240 --> 01:46:36,360 CONTRIBUTE TO THIS ECONOMIC 2645 01:46:36,360 --> 01:46:37,600 STABILITY BEYOND DIRECT 2646 01:46:37,600 --> 01:46:38,120 EMPLOYMENT. 2647 01:46:38,120 --> 01:46:40,080 NEXT SLIDE, PLEASE. 2648 01:46:40,080 --> 01:46:41,680 AND THESE FINANCIAL BURDENS 2649 01:46:41,680 --> 01:46:47,680 DEFINITELY IMPACT FROM THE 2650 01:46:47,680 --> 01:46:49,720 PERSPECTIVE OF PATIENTS AND 2651 01:46:49,720 --> 01:46:52,920 LIMIT MUSCLE AND BRAIN 2652 01:46:52,920 --> 01:46:53,280 RECOVERY. 2653 01:46:53,280 --> 01:46:56,680 ONE PATIENT POINTED OUT THEY 2654 01:46:56,680 --> 01:46:58,360 DIDN'T HAVE RECOVERY SERVICE 2655 01:46:58,360 --> 01:46:59,720 BECAUSE THEY DIDN'T HAVE 2656 01:46:59,720 --> 01:47:01,120 INSURANCE. 2657 01:47:01,120 --> 01:47:05,040 I HAVE BEEN MY OWN RECOVERY 2658 01:47:05,040 --> 01:47:09,400 SERVICE AND NOT SURE HOW TO 2659 01:47:09,400 --> 01:47:11,360 PROMOTE BRAIN AND MUSCLE 2660 01:47:11,360 --> 01:47:14,760 OUTCOMES AND EVEN IF THEY HAVE 2661 01:47:14,760 --> 01:47:17,280 INSURANCE, IT MAY BE FAIRLY 2662 01:47:17,280 --> 01:47:18,000 BRIEF. 2663 01:47:18,000 --> 01:47:19,000 NEXT SLIDE, PLEASE. 2664 01:47:19,000 --> 01:47:22,640 AND POVERTY ISN'T A NEGATIVE 2665 01:47:22,640 --> 01:47:25,720 INCOME BY ITSELF, IT IS ALSO 2666 01:47:25,720 --> 01:47:29,920 LIKELY TO INCREASE AFTER A 2667 01:47:29,920 --> 01:47:33,720 DISABILITY WITH ICU 2668 01:47:33,720 --> 01:47:34,200 HOSPITALIZATION. 2669 01:47:34,200 --> 01:47:38,760 A STUDY BY JAIN SHOWING 2670 01:47:38,760 --> 01:47:40,840 INCREASE IN ELIGIBILITY FOR 2671 01:47:40,840 --> 01:47:41,880 MEDICAID. 2672 01:47:41,880 --> 01:47:43,800 PEOPLE WHO ADD MEDICAID AT 2673 01:47:43,800 --> 01:47:48,280 EVERY LEVEL OF ICU DISABILITY 2674 01:47:48,280 --> 01:47:49,440 ELEVATED AT POST-ICU 2675 01:47:49,440 --> 01:47:50,960 DISABILITY AND WHAT I DON'T 2676 01:47:50,960 --> 01:47:52,440 PRESENT IN THIS PRESENTATION 2677 01:47:52,440 --> 01:47:55,280 IS ALSO HIGHER ODDS OF 2678 01:47:55,280 --> 01:47:56,240 DEVELOPING COGNITIVE 2679 01:47:56,240 --> 01:47:57,600 IMPAIRMENT LATER ON DOWN THE 2680 01:47:57,600 --> 01:47:59,880 ROAD SO VERY TROUBLING 2681 01:47:59,880 --> 01:48:00,240 POVERTY. 2682 01:48:00,240 --> 01:48:01,520 AND WE'RE NOT GOING TO GIVE 2683 01:48:01,520 --> 01:48:03,640 PEOPLE MONEY AS PART OF OUR 2684 01:48:03,640 --> 01:48:05,120 INTERVENTION BUT WE DEFINITELY 2685 01:48:05,120 --> 01:48:07,840 HAVE TO TAKE THIS INTO ACCOUNT 2686 01:48:07,840 --> 01:48:10,520 AND HELP BRIDGE SOME OF THESE 2687 01:48:10,520 --> 01:48:11,680 UNMET NEEDS. 2688 01:48:11,680 --> 01:48:12,760 NEXT SLIDE, PLEASE. 2689 01:48:12,760 --> 01:48:14,360 WE ALSO KNOW OUR PATIENTS 2690 01:48:14,360 --> 01:48:16,560 DON'T LIVE IN THE SAME AREAS 2691 01:48:16,560 --> 01:48:18,960 OR HAVE THE SAME LEVEL OF 2692 01:48:18,960 --> 01:48:20,400 NEIGHBORHOOD AND SOCIAL 2693 01:48:20,400 --> 01:48:20,800 RESOURCES. 2694 01:48:20,800 --> 01:48:21,720 SO THE NEIGHBORHOOD BUILT 2695 01:48:21,720 --> 01:48:23,800 ENVIRONMENT IS A HUGE 2696 01:48:23,800 --> 01:48:25,640 CONTRIBUTOR TO DISABILITY 2697 01:48:25,640 --> 01:48:27,160 AFTER CRITICAL ILLNESS. 2698 01:48:27,160 --> 01:48:28,280 NEXT SLIDE, PLEASE. 2699 01:48:28,280 --> 01:48:29,840 THIS PHOTOGRAPH WHICH WAS 2700 01:48:29,840 --> 01:48:31,560 TAKEN ACTUALLY IN BALTIMORE IS 2701 01:48:31,560 --> 01:48:33,880 ONE OF THE REASONS WHY WE 2702 01:48:33,880 --> 01:48:37,720 MIGHT KNOW THAT DISABILITY 2703 01:48:37,720 --> 01:48:40,360 DEVELOPED DURING ICU STAYS IS 2704 01:48:40,360 --> 01:48:43,760 LESS LIKELY TO RESOLVE IN 2705 01:48:43,760 --> 01:48:45,160 LOW-INCOME NEIGHBORHOODS. 2706 01:48:45,160 --> 01:48:52,840 OUR SIX MINUTE WALK TEST IS 2707 01:48:52,840 --> 01:48:54,680 NOT TRANSLATEIVE TO THIS TYPE 2708 01:48:54,680 --> 01:48:55,720 OF ENVIRONMENT BUT WE HAVE 2709 01:48:55,720 --> 01:48:58,480 PATIENTS WHO NEED TO WALK TO 2710 01:48:58,480 --> 01:49:03,560 GET TO LIKE THE GROCERY STORE 2711 01:49:03,560 --> 01:49:04,840 OR OTHER PLACES. 2712 01:49:04,840 --> 01:49:06,440 NEXT SLIDE, PLEASE. 2713 01:49:06,440 --> 01:49:07,960 THAT MIGHT EXPLAIN WHY THERE 2714 01:49:07,960 --> 01:49:12,160 IS A 10 TO 15 PERCENT INCREASE 2715 01:49:12,160 --> 01:49:14,200 IN DISABILITY BURDEN OVER A 2716 01:49:14,200 --> 01:49:19,760 YEAR AFTER THE ICU STAY. 2717 01:49:19,760 --> 01:49:22,760 EVEN AFTER MECHANICAL CALL 2718 01:49:22,760 --> 01:49:27,720 DISABILITY, A LOT OF OTHER 2719 01:49:27,720 --> 01:49:31,000 FACTORS, CAN BE SEEN UNDER 2720 01:49:31,000 --> 01:49:31,720 NEIGHBORHOOD BUILT SITUATIONS. 2721 01:49:31,720 --> 01:49:33,520 AND IF YOU LIFE IN A LOW 2722 01:49:33,520 --> 01:49:35,160 INCOME NEIGHBORHOOD, YOU ARE 2723 01:49:35,160 --> 01:49:38,160 MORE LIKELY TO DEVELOP 2724 01:49:38,160 --> 01:49:39,440 COGNITIVE IMPAIRMENT. 2725 01:49:39,440 --> 01:49:40,360 NEXT SLIDE, PLEASE. 2726 01:49:40,360 --> 01:49:42,440 NEIGHBORHOOD LEVEL FACTORS ARE 2727 01:49:42,440 --> 01:49:45,280 ASSOCIATED WITH GREATER 2728 01:49:45,280 --> 01:49:49,680 COGNITIVE DECLINE AND ME 2729 01:49:49,680 --> 01:49:50,800 CLINICAL NEUROLOGICAL 2730 01:49:50,800 --> 01:49:54,680 DEGENERATION IN ADULTS BIKE 2731 01:49:54,680 --> 01:49:55,480 ALD HYPER'S DISEASE. 2732 01:49:55,480 --> 01:49:57,080 AND MOMENT ENVIRONMENTS ARE 2733 01:49:57,080 --> 01:50:01,040 ALSO A MAJOR CONTRIBUTOR TO 2734 01:50:01,040 --> 01:50:01,760 DISABILITIES. 2735 01:50:01,760 --> 01:50:05,600 SO HOME ENVIRONMENTS LIKE 2736 01:50:05,600 --> 01:50:07,920 CAPABLE WHICH INTERVENE LIKE 2737 01:50:07,920 --> 01:50:10,840 PAYING A HANDYMAN TO DO 2738 01:50:10,840 --> 01:50:12,280 MODIFICATIONS AND PERSONALIZED 2739 01:50:12,280 --> 01:50:17,040 COACHING ON WAYS TO GET AROUND 2740 01:50:17,040 --> 01:50:18,400 FISCAL INTERVENTIONS AND HAVE 2741 01:50:18,400 --> 01:50:22,400 DIFFERENT APPROACHES IN ACTIVE 2742 01:50:22,400 --> 01:50:27,400 LIVING ARE A MODEL FOR HELPING 2743 01:50:27,400 --> 01:50:30,680 ADL SURVIVORS. 2744 01:50:30,680 --> 01:50:33,360 AND THIS WORK EXPLORES THE 2745 01:50:33,360 --> 01:50:38,480 UNMET NEEDS SPECIFIC TO OLDER 2746 01:50:38,480 --> 01:50:43,240 CRITICAL ILLNESS SURVIVORS, 2747 01:50:43,240 --> 01:50:46,160 UNDERSTANDING TAILORING TO THE 2748 01:50:46,160 --> 01:50:51,600 POPULATIONS AND HOW TO MOVE 2749 01:50:51,600 --> 01:50:52,440 TOWARDS THAT. 2750 01:50:52,440 --> 01:50:56,720 SO YOU MAY BE FAR FROM BEEN 2751 01:50:56,720 --> 01:51:06,880 ABOR, MAINE WHICH IS -- 2752 01:51:06,880 --> 01:51:10,160 BANGOR MAINE WHICH, NEXT 2753 01:51:10,160 --> 01:51:16,680 SLIDE, THE HOSPITAL MAY BE IN 2754 01:51:16,680 --> 01:51:17,200 PORTLAND, MAINE. 2755 01:51:17,200 --> 01:51:20,160 SO IF YOU HAVE TO TRAVEL MORE 2756 01:51:20,160 --> 01:51:24,240 THAN A HUNDRED MILES FOR POST 2757 01:51:24,240 --> 01:51:26,280 ICU CARE, YOU ARE LESS LIKELY 2758 01:51:26,280 --> 01:51:30,360 TO HAVE FOLLOW UP CARE AND 2759 01:51:30,360 --> 01:51:32,520 THEN PEOPLE WHO LIVE FARTHER 2760 01:51:32,520 --> 01:51:34,760 OUT ARE LESS LIKELY TO HAVE 2761 01:51:34,760 --> 01:51:35,760 INTERNET ACCESS. 2762 01:51:35,760 --> 01:51:39,520 SO WHEN BEE THINK ABOUT WHAT 2763 01:51:39,520 --> 01:51:42,440 PEOPLE NEED TO GET TO PLACES 2764 01:51:42,440 --> 01:51:45,760 WHERE THEY NEED 2765 01:51:45,760 --> 01:51:47,480 TRANSPORTATION, NEARLY 700,000 2766 01:51:47,480 --> 01:51:51,920 OLDER ADULTS IN URBAN AREAS 2767 01:51:51,920 --> 01:51:54,520 RELINE ON PUBLIC 2768 01:51:54,520 --> 01:51:56,040 TRANSPORTATION AND HAVE 2769 01:51:56,040 --> 01:51:57,480 BARRIERS TO ATTENDING MEDICAL 2770 01:51:57,480 --> 01:51:57,880 APPOINTMENTS. 2771 01:51:57,880 --> 01:52:02,920 IF YOU LIVE IN AN AREA WITH 2772 01:52:02,920 --> 01:52:05,120 BROKEN SIDEWALKS, FOR EXAMPLE, 2773 01:52:05,120 --> 01:52:11,000 THEY ARE 65 PERCENT LESS 2774 01:52:11,000 --> 01:52:13,480 LIKELY TO REPORT TO MEDICAL 2775 01:52:13,480 --> 01:52:14,080 APPOINTMENTS. 2776 01:52:14,080 --> 01:52:14,600 NEXT SLIDE, PLEASE. 2777 01:52:14,600 --> 01:52:17,800 SO WHEN WE TALK ABOUT HOW TO 2778 01:52:17,800 --> 01:52:19,520 ADDRESS SOCIAL DETERMINANTS OF 2779 01:52:19,520 --> 01:52:21,920 HEALTH AND ARDS WITH 2780 01:52:21,920 --> 01:52:23,120 INTERVENTION FOR DELIVERING 2781 01:52:23,120 --> 01:52:25,160 HELP TO ARDS SURVIVORS, WE 2782 01:52:25,160 --> 01:52:28,440 HAVE TO HAVE A BETTER WAY OF 2783 01:52:28,440 --> 01:52:30,280 DETECTING AND ASKING THE 2784 01:52:30,280 --> 01:52:33,440 QUESTIONS ABOUT HEALTH 2785 01:52:33,440 --> 01:52:34,160 DISPARITIES, VULNERABLE 2786 01:52:34,160 --> 01:52:35,520 POPULATION FACTORS AND 2787 01:52:35,520 --> 01:52:36,360 UNDERSTAND THE NEIGHBORHOODS 2788 01:52:36,360 --> 01:52:36,840 WHERE THEY LIVE. 2789 01:52:36,840 --> 01:52:38,760 WE HAVE TO UNDERSTAND THE 2790 01:52:38,760 --> 01:52:40,480 DISPARITY AT SEVERAL LEVELS, 2791 01:52:40,480 --> 01:52:42,440 NOT JUST THE INDIVIDUAL LEVEL 2792 01:52:42,440 --> 01:52:44,760 BUT THE LEVEL OF THE 2793 01:52:44,760 --> 01:52:47,280 HEALTHCARE SYSTEM, HOW WELL IS 2794 01:52:47,280 --> 01:52:48,760 THE HEALTHCARE SYSTEM EQUIPPED 2795 01:52:48,760 --> 01:52:50,400 TO DEAL WITH THESE NEEDS AND 2796 01:52:50,400 --> 01:52:52,640 THEN WE HAVE TO HAVE 2797 01:52:52,640 --> 01:52:54,640 INTERVENTIONS TO REDUCE THE 2798 01:52:54,640 --> 01:52:55,240 DISPARITIES. 2799 01:52:55,240 --> 01:52:55,840 NEXT SLIDE, PLEASE. 2800 01:52:55,840 --> 01:52:57,440 SO THE SUGGESTION WOULD BE TO 2801 01:52:57,440 --> 01:52:59,920 QUEEN FOR THESE FACTORS IN THE 2802 01:52:59,920 --> 01:53:01,120 E MR. 2803 01:53:01,120 --> 01:53:04,160 IT CAN'T BE SOMETHING WE CHART 2804 01:53:04,160 --> 01:53:07,080 FOR AND WE HAVE TO IDENTIFY 2805 01:53:07,080 --> 01:53:09,000 THE SUBGROUPS EITHER THROUGH 2806 01:53:09,000 --> 01:53:11,440 CLINICAL INTERVENTION OR USING 2807 01:53:11,440 --> 01:53:13,120 STATISTICAL METHODS AND 2808 01:53:13,120 --> 01:53:18,160 UNDERSTANDING HOW THEY 2809 01:53:18,160 --> 01:53:19,600 INTERACT WITH SYSTEMS, OFFER 2810 01:53:19,600 --> 01:53:21,720 SUPPORTS NOT ONLY INDIVIDUALLY 2811 01:53:21,720 --> 01:53:24,600 BUT ADVOCATE FOR POLICY CHANGE 2812 01:53:24,600 --> 01:53:25,000 DOWNSTREAM. 2813 01:53:25,000 --> 01:53:27,600 SO WHAT DO WE NEED TO KNOW? 2814 01:53:27,600 --> 01:53:30,640 WE NEED TO KNOW IF ARDS 2815 01:53:30,640 --> 01:53:31,600 INTERVENTIONS THAT ADDRESS 2816 01:53:31,600 --> 01:53:32,920 SOCIAL DETERMINANTS OF HEALTH 2817 01:53:32,920 --> 01:53:33,680 ARE MORE EFFECTIVE. 2818 01:53:33,680 --> 01:53:35,320 IF WE GIVE THE SAME 2819 01:53:35,320 --> 01:53:37,280 INTERVENTIONS TO JIM AND 2820 01:53:37,280 --> 01:53:39,560 MARVIN IN A CLINICAL TRIAL AND 2821 01:53:39,560 --> 01:53:41,080 EXPECT THE SAME OUTCOMES 2822 01:53:41,080 --> 01:53:42,720 BECAUSE THEY ARE MEDICALLY THE 2823 01:53:42,720 --> 01:53:44,720 SAME, WE ARE REALLY BEING 2824 01:53:44,720 --> 01:53:46,880 SHORTSIGHTED IN TERMS OF WHAT 2825 01:53:46,880 --> 01:53:48,080 IS INFLUENCING PEOPLE FOR 2826 01:53:48,080 --> 01:53:48,440 RECOVERY. 2827 01:53:48,440 --> 01:53:50,360 SO WE NEED TO KNOW IF WE CAN 2828 01:53:50,360 --> 01:53:54,920 ADD SOME OF THESE PIECES IN 2829 01:53:54,920 --> 01:54:02,640 AND IN A WAY THAT PRODUCE 2830 01:54:02,640 --> 01:54:04,000 SOCIAL ENHANCED OUTCOMES. 2831 01:54:04,000 --> 01:54:06,640 SO HIGH RISK HIGH REWARD 2832 01:54:06,640 --> 01:54:10,280 INNOVATION, WE NEED TO DEVELOP 2833 01:54:10,280 --> 01:54:11,600 AND EVALUATE MULTICOMPONENT 2834 01:54:11,600 --> 01:54:12,040 INTERVENTIONS. 2835 01:54:12,040 --> 01:54:15,560 TO MAKE SHE IS SUCCESSFUL, YOU 2836 01:54:15,560 --> 01:54:20,000 HAVE TO HAVE PERSON-CENTERED 2837 01:54:20,000 --> 01:54:23,960 OUTCOMES RESEARCH MODELS WITH 2838 01:54:23,960 --> 01:54:28,200 STAKEHOLDER ENGAGEMENT AND 2839 01:54:28,200 --> 01:54:31,360 PRACTICE-BASED RESEARCH MODELS 2840 01:54:31,360 --> 01:54:35,320 TO FIGURE OUT HOW TO TRAPS 2841 01:54:35,320 --> 01:54:38,080 LATE INTO CLINICAL MODELS AND 2842 01:54:38,080 --> 01:54:40,720 THAT ARE ADAPTABLE AND 2843 01:54:40,720 --> 01:54:43,720 FLEXIBLE LIKE DO CONNOLLY 2844 01:54:43,720 --> 01:54:47,160 MENTIONED TO MAKE SURE WE'RE 2845 01:54:47,160 --> 01:54:51,240 GETTING OUT TO PATIENTS AND 2846 01:54:51,240 --> 01:54:53,080 GETTING AT TRUE BARRIERS OF 2847 01:54:53,080 --> 01:54:55,360 THE INDIVIDUALS AND NOT JUST 2848 01:54:55,360 --> 01:54:56,440 THE PHYSICAL IMPAIRMENTS WE 2849 01:54:56,440 --> 01:54:57,240 NEED TO ADDRESS. 2850 01:54:57,240 --> 01:54:59,640 SO WITH THAT I WILL END IT 2851 01:54:59,640 --> 01:55:02,040 THERE TO LEAVE PLENTY OF TIME 2852 01:55:02,040 --> 01:55:03,360 FOR DISCUSSION, I AM GRATEFUL 2853 01:55:03,360 --> 01:55:04,840 FOR THE INVITATION AND LOOK 2854 01:55:04,840 --> 01:55:06,400 FORWARD TO HEARING YOUR 2855 01:55:06,400 --> 01:55:06,760 QUESTIONS. 2856 01:55:06,760 --> 01:55:07,680 >>THANK YOU, SQUARES SON, 2857 01:55:07,680 --> 01:55:09,680 THAT WAS A FANTASTIC TALK. 2858 01:55:09,680 --> 01:55:10,600 THANKS SO MUCH. 2859 01:55:10,600 --> 01:55:13,280 SO WE ACTUALLY DO HAVE SEVERAL 2860 01:55:13,280 --> 01:55:16,480 QUESTIONS IN THIS CHAT AND I 2861 01:55:16,480 --> 01:55:22,800 AM GOING TO -- WE'RE GOING TO 2862 01:55:22,800 --> 01:55:26,040 ACTUALLY KICK OFF THE PANEL 2863 01:55:26,040 --> 01:55:27,160 DISCUSSION BUT I WILL ASK ONE 2864 01:55:27,160 --> 01:55:30,280 OF THE OTHER QUESTIONS. 2865 01:55:30,280 --> 01:55:31,800 Dr. CONNOLLY WHO SPOKE 2866 01:55:31,800 --> 01:55:33,560 EARLIER IN THE SESSION WANTED 2867 01:55:33,560 --> 01:55:35,400 TO HIGHLIGHT DOING THE 2868 01:55:35,400 --> 01:55:37,800 6-MINUTE WALK AND EVEN IN THE 2869 01:55:37,800 --> 01:55:39,560 BUILT CORRIDOR LIKE WE TALKED 2870 01:55:39,560 --> 01:55:41,960 ABOUT IS NOTHING LIKE THE REAL 2871 01:55:41,960 --> 01:55:42,880 WORLD. 2872 01:55:42,880 --> 01:55:44,520 SO THINKING ABOUT PRAGMATIC 2873 01:55:44,520 --> 01:55:46,680 REAL WORLD FOLLOW UP, PIVOTING 2874 01:55:46,680 --> 01:55:49,400 ON THIS IDEA, HOW DO YOU SEE 2875 01:55:49,400 --> 01:55:50,400 THAT HAPPENING, JASON? 2876 01:55:50,400 --> 01:55:52,080 SO WE'RE GOING TO PROBABLY 2877 01:55:52,080 --> 01:55:54,320 STILL DO THAT SIX-MINUTE WALK 2878 01:55:54,320 --> 01:55:55,920 BUT SHOULD WE BE ADDING 2879 01:55:55,920 --> 01:55:58,320 SOMETHING ELSE TO THAT 2880 01:55:58,320 --> 01:56:00,000 MEASURE? 2881 01:56:00,000 --> 01:56:02,640 WHAT DO YOU SEE PRAGMATIC REAL 2882 01:56:02,640 --> 01:56:03,760 WORLD FOLLOW-UPS LOOKING LIKE 2883 01:56:03,760 --> 01:56:06,400 AND I HAVE ANOTHER RELATED 2884 01:56:06,400 --> 01:56:07,360 MEASUREMENT QUESTION BUT WE'LL 2885 01:56:07,360 --> 01:56:08,160 START WITH THAT FIRST. 2886 01:56:08,160 --> 01:56:10,840 >>THAT IS A GREAT QUESTION 2887 01:56:10,840 --> 01:56:14,840 AND CLINICALLY WHAT I DO IS I 2888 01:56:14,840 --> 01:56:18,440 OFTEN MEASURE PARTICIPATION, 2889 01:56:18,440 --> 01:56:19,080 LIFE-SAVING MOBILITY, HOW 2890 01:56:19,080 --> 01:56:21,040 OFTEN ARE PEOPLE GOING OUT IN 2891 01:56:21,040 --> 01:56:25,280 THE COMMUNITY, HOW MUCH HELP 2892 01:56:25,280 --> 01:56:27,840 DO THEY NEED SO THAT PROMPTS 2893 01:56:27,840 --> 01:56:29,360 KNEE AND A DIFFERENT QUESTION 2894 01:56:29,360 --> 01:56:31,520 VERSUS THE PERSON WHO HAS MORE 2895 01:56:31,520 --> 01:56:33,960 STRENGTH AND NOT GOING OUT, 2896 01:56:33,960 --> 01:56:36,760 THAT TELLS ME THAT THE 2897 01:56:36,760 --> 01:56:38,440 INTERVENTIONS WOULD BE 2898 01:56:38,440 --> 01:56:38,960 DIFFERENT. 2899 01:56:38,960 --> 01:56:40,640 SO MAYBE EXPLORE THE 2900 01:56:40,640 --> 01:56:42,120 MISMATCHES OF CAPACITY VERSUS 2901 01:56:42,120 --> 01:56:43,600 WHAT THEY ARE ACTUALLY DOING 2902 01:56:43,600 --> 01:56:46,640 IS I THINK A REALLY VALUABLE 2903 01:56:46,640 --> 01:56:47,800 TOOL. 2904 01:56:47,800 --> 01:56:49,280 SO NOT REPLACING THE 2905 01:56:49,280 --> 01:56:51,120 SIX-MINUTE WALK WHICH IS 2906 01:56:51,120 --> 01:56:52,240 INCREDIBLE VALUABLE AND GIVES 2907 01:56:52,240 --> 01:56:58,280 YOU GREAT INSIGHT BUT ADDING A 2908 01:56:58,280 --> 01:56:59,440 MEASURE IN, TRANSLATING TO 2909 01:56:59,440 --> 01:57:02,200 GETTING OUT OF THE HOUSE AND 2910 01:57:02,200 --> 01:57:05,400 DOING STUFF. 2911 01:57:05,400 --> 01:57:07,520 >>OKAY, THANK YOU. 2912 01:57:07,520 --> 01:57:11,240 SO SPECIFIC TO YOUR TALK, FROM 2913 01:57:11,240 --> 01:57:13,440 Dr. MOSS, ARE THERE SOCIAL 2914 01:57:13,440 --> 01:57:16,960 DETERMINANT FACTORS THAT ARE 2915 01:57:16,960 --> 01:57:23,640 SPECIFIC INTO ICU OR ARDS 2916 01:57:23,640 --> 01:57:26,560 SURVIVORS WITH SOCIAL 2917 01:57:26,560 --> 01:57:27,640 DETERMINANT FACTORS WITH ARDS 2918 01:57:27,640 --> 01:57:28,480 DISEASE. 2919 01:57:28,480 --> 01:57:29,840 >>THAT IS A GREAT QUESTION 2920 01:57:29,840 --> 01:57:34,000 AND I MIGHT DEFER TO THOSE WHO 2921 01:57:34,000 --> 01:57:39,320 ARE IN THE GROUP WHO ARE 2922 01:57:39,320 --> 01:57:40,320 PHYSICIANS AND HAVE THOSE 2923 01:57:40,320 --> 01:57:44,320 EXPERIENCES BUT I WOULD SAY 2924 01:57:44,320 --> 01:57:45,880 THE DETERMINANTS OF PERSONS 2925 01:57:45,880 --> 01:57:47,880 WITH SIMILAR LOSS OF FUNCTIONS 2926 01:57:47,880 --> 01:57:50,720 TEND TO BE SIMILAR. 2927 01:57:50,720 --> 01:57:53,800 HIP FACT SURE, HEART FAILURE, 2928 01:57:53,800 --> 01:57:54,960 CRITICAL ILLNESS, HAVING 2929 01:57:54,960 --> 01:57:57,320 POVERTY, YOU KNOW, ON TOP OF 2930 01:57:57,320 --> 01:58:00,240 HAVING A DIVERT YACHT TICK 2931 01:58:00,240 --> 01:58:07,480 ABILITY -- GERIATRIC ABILITY 2932 01:58:07,480 --> 01:58:09,120 AND HAVING POVERTY MAKES IT 2933 01:58:09,120 --> 01:58:09,600 WORSE. 2934 01:58:09,600 --> 01:58:11,200 SO THE MEDICAL FACTORS WILL 2935 01:58:11,200 --> 01:58:13,040 DRIVE IT AND THEN THERE WILL 2936 01:58:13,040 --> 01:58:15,080 BE A INTERSECTION BETWEEN 2937 01:58:15,080 --> 01:58:17,520 MEDICAL FACTORS AND SOCIAL 2938 01:58:17,520 --> 01:58:18,360 VULNERABILITY THAT MAGNIFIES 2939 01:58:18,360 --> 01:58:18,880 THE EFFECTS. 2940 01:58:18,880 --> 01:58:20,840 SO IT IS NOT AS CLEAN CUT A 2941 01:58:20,840 --> 01:58:21,160 THING. 2942 01:58:21,160 --> 01:58:22,680 THERE IS A SPECIFIC ONE FOR 2943 01:58:22,680 --> 01:58:24,200 EACH CONDITION. 2944 01:58:24,200 --> 01:58:25,600 I DON'T SEE IT AS 2945 01:58:25,600 --> 01:58:26,160 CONDITION-SPECIFIC. 2946 01:58:26,160 --> 01:58:29,000 I TEND TO BE MORE DYING 2947 01:58:29,000 --> 01:58:31,840 FEDERAL GOVERNMENT TICK IN 2948 01:58:31,840 --> 01:58:32,640 THINKING ABOUT CATASTROPHIC 2949 01:58:32,640 --> 01:58:35,880 LOSS OF FUNCTION AND HOW 2950 01:58:35,880 --> 01:58:37,120 POVERTY OVERPLAYS THAT. 2951 01:58:37,120 --> 01:58:38,880 >>THANKS JASON AND KIND OF TO 2952 01:58:38,880 --> 01:58:41,160 THAT END, THIS PIVOTS BACK TO 2953 01:58:41,160 --> 01:58:42,440 THE MEASUREMENT QUESTION I 2954 01:58:42,440 --> 01:58:42,920 HAD. 2955 01:58:42,920 --> 01:58:44,960 WE TALKED ABOUT CAPTURING 2956 01:58:44,960 --> 01:58:47,080 MUSCLE STRENGTH AND DISABILITY 2957 01:58:47,080 --> 01:58:48,560 AND TALKED ABOUT COGNITIVE 2958 01:58:48,560 --> 01:58:51,640 MEASURES BUT YOU JUST 2959 01:58:51,640 --> 01:58:54,600 HIGHLIGHTED THE IMPORTANCE OF 2960 01:58:54,600 --> 01:58:57,360 SOCIAL DETERMINANTS OF HEALTH 2961 01:58:57,360 --> 01:58:58,440 AND SPECIFIC NEIGHBORHOOD 2962 01:58:58,440 --> 01:59:02,440 DISADVANTAGE SO SHOULD WE BE 2963 01:59:02,440 --> 01:59:07,000 CAPTURING CODE DATA OR ADI IN 2964 01:59:07,000 --> 01:59:09,800 OUR STUDIES FOR CRITICAL 2965 01:59:09,800 --> 01:59:10,920 ILLNESS? 2966 01:59:10,920 --> 01:59:12,240 >>THAT TOOL IS AVAILABLE AND 2967 01:59:12,240 --> 01:59:14,760 EASY TO MATCH TO ADDRESSES SO 2968 01:59:14,760 --> 01:59:16,160 BEING LOW BURDEN, ABSOLUTELY I 2969 01:59:16,160 --> 01:59:18,280 THINK WE SHOULD USE IT. 2970 01:59:18,280 --> 01:59:22,160 I THINK THE QUESTION IS DO 2971 01:59:22,160 --> 01:59:23,440 CLINICIANS KNOW WHAT TO DO 2972 01:59:23,440 --> 01:59:24,120 WITH THE NUMBER? 2973 01:59:24,120 --> 01:59:27,040 BUT I THINK OUR SOCIAL WORK 2974 01:59:27,040 --> 01:59:28,560 ALL RIGHT INTEGRATES THAT KIND 2975 01:59:28,560 --> 01:59:30,960 OF INFORMATION IN 2976 01:59:30,960 --> 01:59:33,320 DECISION-MAKING BUT DOESN'T 2977 01:59:33,320 --> 01:59:35,720 FACTOR INTO RESEARCH AND I 2978 01:59:35,720 --> 01:59:40,240 THINK THAT IS THE BIG BARRIER. 2979 01:59:40,240 --> 01:59:41,760 LIKE PEOPLE WHO USE PUBLIC 2980 01:59:41,760 --> 01:59:45,640 TRANSPORTATION AND I KNOW THE 2981 01:59:45,640 --> 01:59:48,000 SIDEWALK IS ALL BROKEN AND SO 2982 01:59:48,000 --> 01:59:51,920 I HAVE THAT DEEPER LEVEL OF 2983 01:59:51,920 --> 01:59:54,120 UNDERSTANDING ACROSS SEVERAL 2984 01:59:54,120 --> 01:59:56,520 STUDIES TO AT LEAST CATCH 2985 01:59:56,520 --> 01:59:59,560 PEOPLE IN EXTREME POVERTY, 2986 01:59:59,560 --> 02:00:01,280 20 PERCENT OF NEIGHBORHOODS, 2987 02:00:01,280 --> 02:00:02,800 WE'RE ALL URBAN REGARDLESS OF 2988 02:00:02,800 --> 02:00:04,200 NEIGHBORHOODS, YOU ARE GOING 2989 02:00:04,200 --> 02:00:06,000 TO HAVE MORE DIFFICULTY 2990 02:00:06,000 --> 02:00:09,160 ACCESSING HIGH QUALITY THERE. 2991 02:00:09,160 --> 02:00:10,920 >>THANKS, JASON, AND A GREAT 2992 02:00:10,920 --> 02:00:12,680 QUESTION AND FOLLOW UP TO THE 2993 02:00:12,680 --> 02:00:15,200 CONVERSATION WHICH WE WILL 2994 02:00:15,200 --> 02:00:16,880 SAFE FOR THE PANEL DISCUSSION 2995 02:00:16,880 --> 02:00:19,760 SINCE WE'RE NOW TO THE BLOCK 2996 02:00:19,760 --> 02:00:21,120 OF TIME FOR THE PANEL. 2997 02:00:21,120 --> 02:00:23,240 SO FOR THE NEXT FEW MINUTES, I 2998 02:00:23,240 --> 02:00:24,520 GUESS NOW FOUR, I WILL 2999 02:00:24,520 --> 02:00:25,920 SYNTHESIZE WHAT WE HAVE 3000 02:00:25,920 --> 02:00:27,320 LEARNED IN SECTION 1 AND THEN 3001 02:00:27,320 --> 02:00:31,080 WE'RE GOING TO MOVE TO A PANEL 3002 02:00:31,080 --> 02:00:33,160 DISCUSSION THAT JACK AND CAN I 3003 02:00:33,160 --> 02:00:34,040 WILL MOT RATE. 3004 02:00:34,040 --> 02:00:35,800 WE HAVE ALREADY MAPPED OUT 3005 02:00:35,800 --> 02:00:36,800 SOME REALLY IMPORTANT 3006 02:00:36,800 --> 02:00:39,000 QUESTIONS AND THANKS TO ALL OF 3007 02:00:39,000 --> 02:00:41,240 YOU FOR SENDING THOSE TO US 3008 02:00:41,240 --> 02:00:43,840 FOR SPARKING DISCUSSION AND 3009 02:00:43,840 --> 02:00:44,160 THOUGHT. 3010 02:00:44,160 --> 02:00:48,680 SO FIRST, MANY THANKS TO Dr. 3011 02:00:48,680 --> 02:00:52,360 SEVIN, CONNOLLY AND JACKSON 3012 02:00:52,360 --> 02:00:54,320 FOR A FANTASTIC STEP TO THE 3013 02:00:54,320 --> 02:00:55,720 FIRST SESSION IN THIS 3014 02:00:55,720 --> 02:00:56,280 CONFERENCE. 3015 02:00:56,280 --> 02:00:59,240 TO THINK ABOUT SOME DEEP 3016 02:00:59,240 --> 02:01:01,160 POINTS RAISED IN THE FIRST 3017 02:01:01,160 --> 02:01:02,840 SESSION, I WILL RUN THROUGH 3018 02:01:02,840 --> 02:01:03,520 SOME OF THEM. 3019 02:01:03,520 --> 02:01:05,800 I THINK STARTING OUT THAT WE 3020 02:01:05,800 --> 02:01:10,160 WANT TO ANCHOR OUR DISCUSSION 3021 02:01:10,160 --> 02:01:11,480 AND PATH FORWARD IN PATIENT 3022 02:01:11,480 --> 02:01:13,440 STORIES AND THANK YOU AGAIN 3023 02:01:13,440 --> 02:01:18,360 CARLA FOR REALLY HAVING US 3024 02:01:18,360 --> 02:01:18,880 UNDERSTAND THAT. 3025 02:01:18,880 --> 02:01:22,440 ONE SENTENCE THAT CARLA SAID 3026 02:01:22,440 --> 02:01:25,440 THAT STOOD OUT TO ME, ONLY THE 3027 02:01:25,440 --> 02:01:27,800 IC AND REHAB PEOPLE 3028 02:01:27,800 --> 02:01:28,200 UNDERSTAND. 3029 02:01:28,200 --> 02:01:31,320 AND I THINK CARLA'S CALL FOR A 3030 02:01:31,320 --> 02:01:33,000 PATH FORWARD, THAT WAS ONE OF 3031 02:01:33,000 --> 02:01:35,160 THE POINTS THAT SHE MADE WHICH 3032 02:01:35,160 --> 02:01:36,080 WAS IN THINKING ABOUT THE 3033 02:01:36,080 --> 02:01:38,200 NEEDS FOR THE FUTURE OF THIS 3034 02:01:38,200 --> 02:01:40,200 WORK, THERE ARE A FEW 3035 02:01:40,200 --> 02:01:42,520 DIFFERENT ASPECTS OF THIS. 3036 02:01:42,520 --> 02:01:45,000 SO FIRST THINKING ABOUT BETTER 3037 02:01:45,000 --> 02:01:46,280 INFRASTRUCTURE FOR CONDUCTING 3038 02:01:46,280 --> 02:01:48,800 THESE STUDIES AND ALTHOUGH 3039 02:01:48,800 --> 02:01:50,960 RIGHT NOW THAT HAS FOCUSSED A 3040 02:01:50,960 --> 02:01:53,840 LOT TO DATE ON THE ICU AND 3041 02:01:53,840 --> 02:01:55,160 REHAB PEOPLE WHICH ARE A LOT 3042 02:01:55,160 --> 02:01:57,120 OF PEOPLE IN THIS ROOM, WE MAY 3043 02:01:57,120 --> 02:02:01,320 ALSO WANT TO THINK ABOUT 3044 02:02:01,320 --> 02:02:02,200 EXPANDING INFRASTRUCTURE, 3045 02:02:02,200 --> 02:02:03,280 INFORMATION AND PRIMARY CARE 3046 02:02:03,280 --> 02:02:05,440 RESOURCES TO THE COMMUNITY. 3047 02:02:05,440 --> 02:02:07,040 AND TALKING ABOUT RECENT 3048 02:02:07,040 --> 02:02:09,280 ACCESS, ANOTHER KEY POINT THAT 3049 02:02:09,280 --> 02:02:11,000 CAME OUT IN THE SESSION AND 3050 02:02:11,000 --> 02:02:13,840 CHAT TO THE DISCUSSION WAS 3051 02:02:13,840 --> 02:02:15,880 EXPANDING REACH IN UNDERSERVED 3052 02:02:15,880 --> 02:02:17,680 COMMUNITIES AND ALTHOUGH THAT 3053 02:02:17,680 --> 02:02:19,560 WAS THE POINT, AS I READ THAT 3054 02:02:19,560 --> 02:02:22,000 AND THOUGHT ABOUT THAT MORE, I 3055 02:02:22,000 --> 02:02:23,600 REALIZED THERE ARE ACTUALLY A 3056 02:02:23,600 --> 02:02:27,120 COUPLE OF SPECIFIC POPULATIONS 3057 02:02:27,120 --> 02:02:29,880 WE MAY WANT TO THINK ABOUT 3058 02:02:29,880 --> 02:02:31,280 MORE PROPERLY AS WE MOVE 3059 02:02:31,280 --> 02:02:33,800 FORWARD AND THAT INCLUDES 3060 02:02:33,800 --> 02:02:34,600 UNDERSERVED COMMUNITIES BUT 3061 02:02:34,600 --> 02:02:36,000 ALSO RURAL COMMUNITIES THAT 3062 02:02:36,000 --> 02:02:37,840 ARE FARTHER AWAY FROM MAJOR 3063 02:02:37,840 --> 02:02:40,120 MEDICAL CENTERS AND ALSO 3064 02:02:40,120 --> 02:02:41,040 SPECIFIC POPULATIONS AND I DO 3065 02:02:41,040 --> 02:02:43,800 HAVE TO PUT IN A PLUG HERE FOR 3066 02:02:43,800 --> 02:02:45,960 OLDER ADULTS BECAUSE THEY MAY 3067 02:02:45,960 --> 02:02:49,000 HAVE MORE DISABILITIES AND 3068 02:02:49,000 --> 02:02:50,400 MOBILITY LIMITATIONS AFTER 3069 02:02:50,400 --> 02:02:51,920 CRITICAL ILLNESS THAT MAY 3070 02:02:51,920 --> 02:02:53,640 PREVENT THEM FROM COMING TO A 3071 02:02:53,640 --> 02:02:56,040 RECOVERY PROGRAM SUCH AS THE 3072 02:02:56,040 --> 02:02:57,560 FANTASTIC ONE AT VANDERBILT. 3073 02:02:57,560 --> 02:02:59,040 SO THINKING ABOUT THOSE 3074 02:02:59,040 --> 02:02:59,760 SPECIFIC POPULATIONS. 3075 02:02:59,760 --> 02:03:01,240 IN TERMS OF MEASUREMENT, I 3076 02:03:01,240 --> 02:03:03,040 THINK WE HAVE BEEN CHALLENGED 3077 02:03:03,040 --> 02:03:06,400 WITH THINKING ABOUT HOW THE 3078 02:03:06,400 --> 02:03:07,560 TESTS WE'RE USING SOMETIMES 3079 02:03:07,560 --> 02:03:09,640 FAIL TO CORRESPOND TO REAL 3080 02:03:09,640 --> 02:03:11,240 LIFE SITUATIONS AND 3081 02:03:11,240 --> 02:03:11,640 CHALLENGES. 3082 02:03:11,640 --> 02:03:16,360 AND JIM DID A WONDERFUL JOB IN 3083 02:03:16,360 --> 02:03:17,160 HIGHLIGHTING THIS. 3084 02:03:17,160 --> 02:03:22,840 AND A POINT THAT ALSO CAME UP 3085 02:03:22,840 --> 02:03:23,760 IN BRONWEN'S TALK. 3086 02:03:23,760 --> 02:03:27,800 HOW DO WE KNOW THAT IT 3087 02:03:27,800 --> 02:03:28,840 TRANSLATES TO MUSCLE STRENGTH 3088 02:03:28,840 --> 02:03:30,760 AND ABILITY TO DO A DESIRED 3089 02:03:30,760 --> 02:03:34,160 TASK, VERY IMPORTANT. 3090 02:03:34,160 --> 02:03:35,960 SO WE FOCUS ON THE VALUE AND 3091 02:03:35,960 --> 02:03:37,600 HOW TO THINK ABOUT THE DESIGN 3092 02:03:37,600 --> 02:03:39,200 OF FUTURE STUDIES TO CONSIDER 3093 02:03:39,200 --> 02:03:40,680 THAT AND ALSO WHICH WE WILL 3094 02:03:40,680 --> 02:03:43,040 TALK ABOUT IN THE PANEL, HOW 3095 02:03:43,040 --> 02:03:45,160 PATIENTS CAN ADAPT AND MAY 3096 02:03:45,160 --> 02:03:47,080 ADAPT TO WHAT THEIR OUTCOME 3097 02:03:47,080 --> 02:03:47,840 GOAL IS. 3098 02:03:47,840 --> 02:03:51,000 AND THEN I THINK ADDING IN THE 3099 02:03:51,000 --> 02:03:52,760 ELEMENT OF SOCIAL DETERMINANTS 3100 02:03:52,760 --> 02:03:54,800 OF HEALTH, BOTH IN TERMS OF -- 3101 02:03:54,800 --> 02:03:57,000 AND ACTUALLY I DON'T WANT TO 3102 02:03:57,000 --> 02:04:00,360 CALL THESE -- I THINK THEY ARE 3103 02:04:00,360 --> 02:04:03,240 VERY DIFFERENT FACTORS IN THIS 3104 02:04:03,240 --> 02:04:04,480 VERY BROAD CATEGORY SO 3105 02:04:04,480 --> 02:04:07,560 THINKING ON THE ONE END OF 3106 02:04:07,560 --> 02:04:09,160 CRITICAL FACTORS SUCH AS 3107 02:04:09,160 --> 02:04:10,280 SOCIAL SUPPORT AND SOCIAL 3108 02:04:10,280 --> 02:04:11,440 ISOLATION, WOULD HE KNOW THIS 3109 02:04:11,440 --> 02:04:11,880 IS IMPORTANT. 3110 02:04:11,880 --> 02:04:14,880 WE ARE NOT CURRENTLY 3111 02:04:14,880 --> 02:04:15,560 SYSTEMATICALLY CAP COOPERING 3112 02:04:15,560 --> 02:04:17,080 THIS IN OUR STUDIES AND 3113 02:04:17,080 --> 02:04:18,560 SOMETHING WE NEED TO THINK 3114 02:04:18,560 --> 02:04:20,360 ABOUT MOVING FORWARD BECAUSE 3115 02:04:20,360 --> 02:04:22,240 IT MAY BE RIGHT FOR 3116 02:04:22,240 --> 02:04:22,680 INTERVENTION. 3117 02:04:22,680 --> 02:04:25,240 I HAVE A PATIENT WHO IS A ARDS 3118 02:04:25,240 --> 02:04:27,880 COVID SURVIVOR, HAS SEVERE 3119 02:04:27,880 --> 02:04:29,680 IMPAIRMENTS AND ACTUALLY COMES 3120 02:04:29,680 --> 02:04:32,640 FROM AN UNDERSERVED COMMUNITY 3121 02:04:32,640 --> 02:04:34,960 BUT HAS SUCH STRONG SOCIAL 3122 02:04:34,960 --> 02:04:36,360 SUPPORT FROM HIS FAMILY THAT A 3123 02:04:36,360 --> 02:04:39,560 YEAR OUT HE HAS RECEIVED 3124 02:04:39,560 --> 02:04:41,040 FUNCTIONAL HEALTH RECOVERY, 3125 02:04:41,040 --> 02:04:43,560 MENTAL HEALTH RECOVERY, BACK 3126 02:04:43,560 --> 02:04:45,160 AT WORK PART-TIME, 67 AND 3127 02:04:45,160 --> 02:04:48,720 STILL WORKS, AND HAS A BIT OF 3128 02:04:48,720 --> 02:04:51,720 A MILD COGNITIVE IMPAIRMENT. 3129 02:04:51,720 --> 02:04:53,960 SO THESE IMPAIRMENTS CAN 3130 02:04:53,960 --> 02:04:55,000 OVERCOME, PEOPLE CAN RECOVER 3131 02:04:55,000 --> 02:04:56,760 WITH THINKING ABOUT HOW 3132 02:04:56,760 --> 02:04:59,560 IMPORTANT SOCIAL SUPPORT IS 3133 02:04:59,560 --> 02:05:01,800 AND THEN OF COURSE THE 3134 02:05:01,800 --> 02:05:03,040 COGNITIVE BARRIERS THAT WAS 3135 02:05:03,040 --> 02:05:04,200 HIGHLIGHTED IN THIS TALK. 3136 02:05:04,200 --> 02:05:08,960 SO I HAVE NOW SPOKEN MY FIVE 3137 02:05:08,960 --> 02:05:10,880 MINUTES AND DON'T WANT TO GO 3138 02:05:10,880 --> 02:05:12,400 OVER TIME SO THIS WILL BE A 3139 02:05:12,400 --> 02:05:14,560 GOOD TIME TO SEGUE INTO THE 3140 02:05:14,560 --> 02:05:16,240 PANEL DISCUSSION AND TURN IT 3141 02:05:16,240 --> 02:05:16,920 OVER TO JACK. 3142 02:05:16,920 --> 02:05:18,640 >>THIS COULD BE AWESOME BUT 3143 02:05:18,640 --> 02:05:20,240 WE HAVE SEVEN HOURS WORTH OF 3144 02:05:20,240 --> 02:05:25,120 THINGS THAT WE NEED TO TALK 3145 02:05:25,120 --> 02:05:26,240 ABOUT COMPRESSED IN 23 MINUTES 3146 02:05:26,240 --> 02:05:28,840 SO THAT MEANS AT SOME LEVEL, 3147 02:05:28,840 --> 02:05:30,920 THERE ARE FIVE BROAD STATIC 3148 02:05:30,920 --> 02:05:32,760 AREAS WE NEED TO COVER AND 3149 02:05:32,760 --> 02:05:35,200 THINK ABOUT AS A FOUR MINUTE 3150 02:05:35,200 --> 02:05:35,800 TALK CYCLE. 3151 02:05:35,800 --> 02:05:38,000 EVERY TIME ONE OF THOSE FIVE 3152 02:05:38,000 --> 02:05:39,360 MINUTE NUMBERS COMES UP, WE 3153 02:05:39,360 --> 02:05:41,520 SHOULD BE MOVING ON. 3154 02:05:41,520 --> 02:05:42,760 SO LET'S START WITH -- THERE 3155 02:05:42,760 --> 02:05:45,160 ARE A WHOLE BUNCH OF QUESTIONS 3156 02:05:45,160 --> 02:05:47,040 ASKING WHAT THE NEXT 3157 02:05:47,040 --> 02:05:48,520 GENERATION MEASUREMENT LOOKS 3158 02:05:48,520 --> 02:05:51,880 LIKE, WAYS SORT OF BRINGING 3159 02:05:51,880 --> 02:05:58,400 TECHNOLOGY TO DO IN VIVO, IN 3160 02:05:58,400 --> 02:05:59,200 PEOPLE'S HOMES, MEASUREMENTS 3161 02:05:59,200 --> 02:06:00,840 OF HOW THEY ARE DOING AND I 3162 02:06:00,840 --> 02:06:04,000 THINK THERE COULD BE A LOT OF 3163 02:06:04,000 --> 02:06:05,960 ENTHUSIASM STARTING WITH JIM 3164 02:06:05,960 --> 02:06:08,000 AND THEN WHAT YOU THINK YOUR 3165 02:06:08,000 --> 02:06:11,000 NEAR HORIZON LOOKS LIKE FOR 3166 02:06:11,000 --> 02:06:11,880 NEXT GENERATION MEASUREMENTS. 3167 02:06:11,880 --> 02:06:13,560 >>YEAH, I AM SURE. 3168 02:06:13,560 --> 02:06:14,920 I WILL BE QUICK. 3169 02:06:14,920 --> 02:06:16,320 I THINK THAT'S EXACTLY THE 3170 02:06:16,320 --> 02:06:18,840 RIGHT AVENUE THAT WE NEED TO 3171 02:06:18,840 --> 02:06:23,080 BE WALKING DOWN, THAT IS 3172 02:06:23,080 --> 02:06:25,800 EITHER IN VIVO OR SOME KIND OF 3173 02:06:25,800 --> 02:06:27,280 VIRTUAL REALITY WHICH DOES 3174 02:06:27,280 --> 02:06:28,240 EXIST. 3175 02:06:28,240 --> 02:06:30,920 IT IS CUMBERSOME STILL AND 3176 02:06:30,920 --> 02:06:33,320 SORT OF IN DEVELOPMENT BUT 3177 02:06:33,320 --> 02:06:35,760 EVEN VIRTUAL REALITY LIKELY 3178 02:06:35,760 --> 02:06:36,680 CAPTURES REAL WORD FUNCTIONS 3179 02:06:36,680 --> 02:06:38,320 BETTER THAN WHAT WE USED. 3180 02:06:38,320 --> 02:06:41,720 THERE ARE SOME COGNITIVE TESTS 3181 02:06:41,720 --> 02:06:42,400 DEVELOPED IN THE UNITED 3182 02:06:42,400 --> 02:06:44,640 KINGDOM WHICH HAVE A SLIGHTLY 3183 02:06:44,640 --> 02:06:46,800 DIFFERENT APPROACH. 3184 02:06:46,800 --> 02:06:50,240 THEY HAVE YOU EXPLICITLY WORK 3185 02:06:50,240 --> 02:06:55,200 ON REAL WORLD COGNITIVE PATHS 3186 02:06:55,200 --> 02:06:57,160 THAT MIMIC REAL WORLD 3187 02:06:57,160 --> 02:06:58,560 COGNITIVE PATHS SO I THINK 3188 02:06:58,560 --> 02:06:59,240 THAT IS HELPFUL. 3189 02:06:59,240 --> 02:07:00,720 I THINK OTHER THINGS WE NEED 3190 02:07:00,720 --> 02:07:02,920 TO THINK ABOUT WOULD BE 3191 02:07:02,920 --> 02:07:05,240 LOOKING IT THE WAY WE ENGAUGE 3192 02:07:05,240 --> 02:07:07,040 SOCIAL MEDIA, FOR INSTANCE, 3193 02:07:07,040 --> 02:07:10,600 ARE THERE CHANGES OVER TIME IN 3194 02:07:10,600 --> 02:07:11,040 MISSPELLINGS. 3195 02:07:11,040 --> 02:07:13,440 ON TWITTER, ARE THERE CHANGES 3196 02:07:13,440 --> 02:07:15,000 IN CONTENT, ON FACEBOOK 3197 02:07:15,000 --> 02:07:16,520 POSTINGS, ARE THERE ERRORS IN 3198 02:07:16,520 --> 02:07:18,120 TEXTING THAT PEOPLE ARE 3199 02:07:18,120 --> 02:07:19,640 STARTING TO ENGAGE IN, THINGS 3200 02:07:19,640 --> 02:07:21,480 OF THAT SORT THAT ARE REAL 3201 02:07:21,480 --> 02:07:21,920 WORLD. 3202 02:07:21,920 --> 02:07:23,840 THIS IS GOING TO REQUIRE 3203 02:07:23,840 --> 02:07:25,720 LETTING GO OF AN APPROACH THAT 3204 02:07:25,720 --> 02:07:28,360 IS PRETTY COMFORTABLE WHICH IS 3205 02:07:28,360 --> 02:07:31,880 THIS AND I AM READY TO DO THAT 3206 02:07:31,880 --> 02:07:35,520 AND HOPEFULLY OTHERS WILL 3207 02:07:35,520 --> 02:07:36,080 JOIN. 3208 02:07:36,080 --> 02:07:37,480 >>ANYBODY WANT TO GO NEXT AND 3209 02:07:37,480 --> 02:07:40,920 THEN WE WILL GO TO JASON? 3210 02:07:40,920 --> 02:07:41,960 >>THANK YOU, I AGREE. 3211 02:07:41,960 --> 02:07:44,960 IT IS A WAY FORWARD TO MEASURE 3212 02:07:44,960 --> 02:07:46,520 PHYSICAL FUNCTION, THERE MAY 3213 02:07:46,520 --> 02:07:49,280 BE A FEW PRACTICAL ASPECTS TO 3214 02:07:49,280 --> 02:07:52,360 CONSIDER IN TERMS OF HOW DO WE 3215 02:07:52,360 --> 02:07:53,840 HAVE UP WITH DEVICE THAT 3216 02:07:53,840 --> 02:07:57,120 ALLOWS US TO FOLLOW A PATIENT 3217 02:07:57,120 --> 02:07:58,160 AROUND IN THEIR ENVIRONMENT, 3218 02:07:58,160 --> 02:08:02,080 AND I THINK A SETUP IS 3219 02:08:02,080 --> 02:08:03,480 REQUIRED TO MEASURE PHYSICAL 3220 02:08:03,480 --> 02:08:04,720 FUNCTION IN THE HOME 3221 02:08:04,720 --> 02:08:07,240 DEVELOPMENT WHICH WOULD BE 3222 02:08:07,240 --> 02:08:08,400 FANTASTIC AND REAL WORLD 3223 02:08:08,400 --> 02:08:11,480 BECAUSE THEN YOU CAN SEE THE 3224 02:08:11,480 --> 02:08:12,880 PHYSICAL AREAS THAT IS 3225 02:08:12,880 --> 02:08:15,800 IMPACTING THEM AND WE CAN 3226 02:08:15,800 --> 02:08:16,400 ADAPT THAT. 3227 02:08:16,400 --> 02:08:20,640 I THINK THERE'S SOME PRACTICAL 3228 02:08:20,640 --> 02:08:23,600 LOGISTICAL ISSUES AROUND 3229 02:08:23,600 --> 02:08:24,600 GETTING TECHNOLOGY IN THERE TO 3230 02:08:24,600 --> 02:08:29,120 ALLOW US TO SEE THE WHOLE 3231 02:08:29,120 --> 02:08:30,160 ENVIRONMENT EASILY VERSUS SOME 3232 02:08:30,160 --> 02:08:33,480 TESTS THAT THEY CAN DO IN ONE 3233 02:08:33,480 --> 02:08:35,680 PHYSICAL TEST LIKE SITTING ON 3234 02:08:35,680 --> 02:08:37,640 A TABLE OR AROUND THE HOUSE 3235 02:08:37,640 --> 02:08:42,480 AND LOGISTICS AROUND IT. 3236 02:08:42,480 --> 02:08:45,640 I GUESS USING DIGITAL 3237 02:08:45,640 --> 02:08:48,240 COGNITIVE AND HOME HEALTH AND 3238 02:08:48,240 --> 02:08:50,960 THINKING ABOUT THE AGE OF THE 3239 02:08:50,960 --> 02:08:54,800 POPULATION, THERE ARE STUDIES 3240 02:08:54,800 --> 02:08:57,400 FOR PEOPLE WHO ARE OLDER AND 3241 02:08:57,400 --> 02:08:59,160 BEING TECH SAVVY AND SO FORTH 3242 02:08:59,160 --> 02:09:01,400 BUT YES, I WOULD LIKE TO THINK 3243 02:09:01,400 --> 02:09:05,760 OF THAT IN TERMS OF THE MOMENT 3244 02:09:05,760 --> 02:09:06,160 ENVIRONMENT. 3245 02:09:06,160 --> 02:09:07,800 >>THANK YOU AND WHILE YOU ARE 3246 02:09:07,800 --> 02:09:09,480 GETTING READY, I WILL REMIND 3247 02:09:09,480 --> 02:09:11,320 PEOPLE THE CHAT IS HIGHLY 3248 02:09:11,320 --> 02:09:14,280 VISIBLE AND IS A GREAT PLACE 3249 02:09:14,280 --> 02:09:15,200 TO MAKE ADDITIONAL POINTS 3250 02:09:15,200 --> 02:09:16,840 SINCE WE ARE NOT GOING TO GET 3251 02:09:16,840 --> 02:09:20,840 THROUGH ALL OF THEM IN 25 3252 02:09:20,840 --> 02:09:21,160 MINUTES. 3253 02:09:21,160 --> 02:09:22,200 GO AHEAD. 3254 02:09:22,200 --> 02:09:26,720 >>YES, THANK YOU AND I AGREE 3255 02:09:26,720 --> 02:09:31,000 THE DIGITAL TECHNOLOGY HAS SO 3256 02:09:31,000 --> 02:09:32,480 MUCH PROMISE AND ARE THE 3257 02:09:32,480 --> 02:09:33,800 COMPONENTS MATCHING UP TO WHAT 3258 02:09:33,800 --> 02:09:34,760 WE ARE SEEING. 3259 02:09:34,760 --> 02:09:35,680 EXTENDING THAT OUT TO THE 3260 02:09:35,680 --> 02:09:37,920 COMMUNITY, I HAVE GIVEN A LOT 3261 02:09:37,920 --> 02:09:39,800 OF THOUGHT TO USING PS AND 3262 02:09:39,800 --> 02:09:44,680 OTHER THINGS AND THEN HOW FAR 3263 02:09:44,680 --> 02:09:46,320 ARE FAR ARE PEOPLE GETTING 3264 02:09:46,320 --> 02:09:48,720 AWAY FROM THEIR HOME? 3265 02:09:48,720 --> 02:09:51,280 ARE THEY MOVING BACK TO PLACES 3266 02:09:51,280 --> 02:09:53,120 THEY WANT TO GO BECAUSE I 3267 02:09:53,120 --> 02:09:59,160 THINK TOO OFTEN WE ESPECIALLY 3268 02:09:59,160 --> 02:10:02,680 TEND TO STOP BEFORE BECOMING 3269 02:10:02,680 --> 02:10:03,840 INDEPENDENT OR AMBULATORY, 3270 02:10:03,840 --> 02:10:09,240 ONCE YOU CAN WALK 150 FEET AND 3271 02:10:09,240 --> 02:10:10,640 OUT THE DOOR, YOU ARE SAID TO 3272 02:10:10,640 --> 02:10:13,440 BE ABLE TO MEET ALL OF THEIR 3273 02:10:13,440 --> 02:10:15,080 SCORES BUT I DON'T THINK THAT 3274 02:10:15,080 --> 02:10:17,320 TRANSLATES WELL TO A PATIENT 3275 02:10:17,320 --> 02:10:19,280 WHO HAS TO WALK TWAOUPB 3276 02:10:19,280 --> 02:10:27,480 SIDEWALKS I SHOWED -- WALK 3277 02:10:27,480 --> 02:10:29,320 DOWN THE SIDEWALKS I SHOWED 3278 02:10:29,320 --> 02:10:32,840 YOU AND THEN TO THE BUS STOP. 3279 02:10:32,840 --> 02:10:34,440 I THINK TECHNOLOGIES BUT 3280 02:10:34,440 --> 02:10:36,400 POLICIES FOR RURAL COMMUNITIES 3281 02:10:36,400 --> 02:10:39,440 OR MAKING SURE THERE IS 3282 02:10:39,440 --> 02:10:44,480 DIGITAL EQUITY IN LOWER INCOME 3283 02:10:44,480 --> 02:10:45,440 NEIGHBORHOODS IN URBAN 3284 02:10:45,440 --> 02:10:47,120 DEVELOPMENTS AND SOMETHING WE 3285 02:10:47,120 --> 02:10:51,640 CAN DO TO SET PEOPLE UP WITH 3286 02:10:51,640 --> 02:10:53,600 DIGITAL DEVICES, I KNOW THE VA 3287 02:10:53,600 --> 02:10:56,560 DOES THIS AND DON'T KNOW WHY 3288 02:10:56,560 --> 02:10:59,480 WE CAN'T HAVE THAT FOR 3289 02:10:59,480 --> 02:11:00,280 EVERYONE. 3290 02:11:00,280 --> 02:11:01,600 >>AND -- 3291 02:11:01,600 --> 02:11:02,680 [INDISCERNIBLE] 3292 02:11:02,680 --> 02:11:10,000 CARLA, YOU WANT TO TALK TO GO 3293 02:11:10,000 --> 02:11:10,320 NEXT? 3294 02:11:10,320 --> 02:11:12,240 >> YES, I WILL SAY WE HAD 3295 02:11:12,240 --> 02:11:13,760 MANY IDEAS WHAT WE WERE GOING 3296 02:11:13,760 --> 02:11:15,600 TO LEARN FROM THESE CASES AND 3297 02:11:15,600 --> 02:11:18,480 WE FOUND SO MUCH LOW-HANGING 3298 02:11:18,480 --> 02:11:20,880 FRUIT, LIKE ALL THE CONCRETE 3299 02:11:20,880 --> 02:11:22,600 THINGS WE THINK ARE ALREADY 3300 02:11:22,600 --> 02:11:24,760 HAPPENING THAT ARE NOT 3301 02:11:24,760 --> 02:11:27,480 HAPPENING ARE -- THERE'S JUST 3302 02:11:27,480 --> 02:11:30,040 AN ENDLESS AMOUNT OF DATA THAT 3303 02:11:30,040 --> 02:11:32,240 WE NEED TO GET IN THIS AREA. 3304 02:11:32,240 --> 02:11:36,000 SO I ALSO, WHILE ASPIRING TO 3305 02:11:36,000 --> 02:11:38,840 FUTURE TECH, I HAVE TO REMIND 3306 02:11:38,840 --> 02:11:40,000 OURSELVES TO LIKE BRING US 3307 02:11:40,000 --> 02:11:41,880 DOWN AND WE CAN USE THE TOOLS 3308 02:11:41,880 --> 02:11:43,520 WE ALREADY HAVE AND WE CAN USE 3309 02:11:43,520 --> 02:11:44,920 THEM IN A DIFFERENT WAY. 3310 02:11:44,920 --> 02:11:47,520 SO FOR EXAMPLE EVEN THE 3311 02:11:47,520 --> 02:11:49,360 SIX-MINUTE WALK WHICH IS 3312 02:11:49,360 --> 02:11:50,960 WIDELY USED, EVEN AT THE 3313 02:11:50,960 --> 02:11:53,280 HALLWAY WE ARE' USING TO 3314 02:11:53,280 --> 02:11:55,000 WALK-IN CLINIC IS NOT THE SAME 3315 02:11:55,000 --> 02:11:56,480 AS THE STREETS THE PATIENT 3316 02:11:56,480 --> 02:11:59,640 WILL BE ON BUT WE CAN STARTIZE 3317 02:11:59,640 --> 02:12:02,720 AND GET A LOT OF DATA FROM. 3318 02:12:02,720 --> 02:12:04,320 WE CAN ALSO AND THIS HAS BEEN 3319 02:12:04,320 --> 02:12:06,680 DIFFERENT FOR US IN THE 3320 02:12:06,680 --> 02:12:08,720 CLINICAL SETTING, WE CAN USE 3321 02:12:08,720 --> 02:12:10,520 IT AS AN INTERVENTIONAL TOOL. 3322 02:12:10,520 --> 02:12:14,560 A PATIENT WILL SAY I AM FINE, 3323 02:12:14,560 --> 02:12:17,880 GOING BACK TO WORK AND WE WILL 3324 02:12:17,880 --> 02:12:20,480 SAY YOUR SIX-MINUTE WALK IS 3325 02:12:20,480 --> 02:12:22,400 ONLY 47 PERCENT PREDICTIVE AND 3326 02:12:22,400 --> 02:12:25,120 THEY ARE LIKE OH MY GOSH, HOW 3327 02:12:25,120 --> 02:12:27,120 CAN I MAKE THAT NUMBER BETTER, 3328 02:12:27,120 --> 02:12:28,680 THAT DATA IS VERY MOTIVATING 3329 02:12:28,680 --> 02:12:31,520 TO ME AND NOW WE'RE USING THAT 3330 02:12:31,520 --> 02:12:34,600 AS AN INTERVENTION TO INCREASE 3331 02:12:34,600 --> 02:12:35,120 PHYSICAL THERAPY. 3332 02:12:35,120 --> 02:12:37,840 I WILL SAY NOT BEING AN EARLY 3333 02:12:37,840 --> 02:12:39,840 ADOPTER OF TECH, THE 3334 02:12:39,840 --> 02:12:40,720 TELEMEDICINE VERSION OF 3335 02:12:40,720 --> 02:12:42,160 OUTREACH FOR THESE PATIENTS 3336 02:12:42,160 --> 02:12:44,560 HAS ALLOWED US TO OVERCOME A 3337 02:12:44,560 --> 02:12:48,680 LOT OF BARRIERS AND, YOU KNOW, 3338 02:12:48,680 --> 02:12:50,200 RURAL TENNESSEE NO EXCEPTION 3339 02:12:50,200 --> 02:12:51,960 IN TERMS OF UNDER RESOURCING 3340 02:12:51,960 --> 02:12:56,640 AND WE HAD FEARS WHEN WE 3341 02:12:56,640 --> 02:12:58,040 STARTED OUR TELEMEDICINE 3342 02:12:58,040 --> 02:12:59,640 PROGRAM AND ADDRESSED IN CHAT, 3343 02:12:59,640 --> 02:13:01,520 WE WOULD NOT BE ABLE TO MEET 3344 02:13:01,520 --> 02:13:03,320 THE NEEDS OF RURAL 3345 02:13:03,320 --> 02:13:04,840 POPULATIONS, WOULD NOT BE ABLE 3346 02:13:04,840 --> 02:13:06,320 TO SEE OLDER POPULATIONS 3347 02:13:06,320 --> 02:13:09,400 BECAUSE OF THEIR DIFFICULTY 3348 02:13:09,400 --> 02:13:10,760 ACCESSING TECH. 3349 02:13:10,760 --> 02:13:12,600 BUT GOOD NEWS! THEY SEEM TO 3350 02:13:12,600 --> 02:13:13,680 ALL HAVE GRANDCHILDREN AND 3351 02:13:13,680 --> 02:13:16,520 FOUND A WAY TO GET ON THE 3352 02:13:16,520 --> 02:13:18,800 VISIT AND IF ANYTHING GOOD CAN 3353 02:13:18,800 --> 02:13:22,200 BE ASCRIBED TO COVID, THE 3354 02:13:22,200 --> 02:13:23,280 FACILITY WITH TELEMEDICINE IS 3355 02:13:23,280 --> 02:13:24,880 ONE OF THOSE THINGS. 3356 02:13:24,880 --> 02:13:27,200 LIKE WE MOVED FOR YEARS TO GET 3357 02:13:27,200 --> 02:13:28,680 A TELEMEDICINE PROGRAM GOING 3358 02:13:28,680 --> 02:13:30,440 AND STARTED IT IN 3359 02:13:30,440 --> 02:13:33,280 DECEMBER 2019 AND THEN IN 3360 02:13:33,280 --> 02:13:35,040 MARCH 2020, WE HAD 3361 02:13:35,040 --> 02:13:36,280 TELEMEDICINE OVERNIGHT AND ALL 3362 02:13:36,280 --> 02:13:38,040 THE BARRIERS FELL AWAY AND 3363 02:13:38,040 --> 02:13:40,880 SOMEHOW WE WERE DOING 3364 02:13:40,880 --> 02:13:41,280 TELEMEDICINE. 3365 02:13:41,280 --> 02:13:42,880 SO THAT WAS BOTH FRUSTRATING 3366 02:13:42,880 --> 02:13:43,440 AND REFRESHING. 3367 02:13:43,440 --> 02:13:45,720 SO WE KNOW WE CAN DO HARD 3368 02:13:45,720 --> 02:13:47,080 THINGS AND OVERCOME BARRIERS 3369 02:13:47,080 --> 02:13:50,000 IF THERE IS WILL AND, YOU 3370 02:13:50,000 --> 02:13:52,320 KNOW, FUNDING AND MOTIVATION 3371 02:13:52,320 --> 02:13:53,160 TO DO SO. 3372 02:13:53,160 --> 02:13:56,640 SO WHILE WE ARE THINKING ABOUT 3373 02:13:56,640 --> 02:13:58,880 THESE NEXT-GEN MEASUREMENTS, I 3374 02:13:58,880 --> 02:14:01,400 WOULD SAY DON'T THROW AWAY THE 3375 02:14:01,400 --> 02:14:02,920 SIMPLE MEASURES WE CAN USE AND 3376 02:14:02,920 --> 02:14:04,520 GET A LOT OF INFORMATION FROM 3377 02:14:04,520 --> 02:14:08,240 THAT ARE ALREADY AVAILABLE AND 3378 02:14:08,240 --> 02:14:09,520 YOU KNOW INCREMENTALLY USE THE 3379 02:14:09,520 --> 02:14:11,240 TECH THAT IS AVAILABLE TO 3380 02:14:11,240 --> 02:14:15,680 SQUEAK WHAT WE CAN -- TWEAK 3381 02:14:15,680 --> 02:14:18,520 WHAT WE CAN DO LIKE TODAY. 3382 02:14:18,520 --> 02:14:20,360 >>AWESOME, LOVE YOU GUYS, 3383 02:14:20,360 --> 02:14:24,200 SPENT FOUR MINUTES WHICH MIGHT 3384 02:14:24,200 --> 02:14:28,840 BE THE SHORTEST SO -- 3385 02:14:28,840 --> 02:14:29,360 [INDISCERNIBLE] 3386 02:14:29,360 --> 02:14:30,680 >>JACK, WE COVERED 3387 02:14:30,680 --> 02:14:32,840 TELEMEDICINE SO CAN WE PLEASE 3388 02:14:32,840 --> 02:14:34,800 CROSS THAT OFF OUR PLAN? 3389 02:14:34,800 --> 02:14:35,520 >> YES. 3390 02:14:35,520 --> 02:14:39,240 NEXT ONE ACCIDENT WE TALKED A 3391 02:14:39,240 --> 02:14:41,000 LOT ABOUT FIXING MUSCLES IN 3392 02:14:41,000 --> 02:14:43,840 BRAINS BUT FOR MANY OF US, OUR 3393 02:14:43,840 --> 02:14:45,960 EYES DON'T WORK TERRIBLY WELL 3394 02:14:45,960 --> 02:14:48,280 AND IT TURNS OUT INSTEAD OF 3395 02:14:48,280 --> 02:14:52,320 RESHAPING OUR EYES, WE HAVE A 3396 02:14:52,320 --> 02:14:55,520 UBIQUITOUS FUNCTION THAT 3397 02:14:55,520 --> 02:14:58,120 ALLOWS US TO SEE BETTER IN 3398 02:14:58,120 --> 02:14:58,600 LIGHT. 3399 02:14:58,600 --> 02:15:02,000 WITH THE NIH AND THEIR 3400 02:15:02,000 --> 02:15:07,200 DIVERSITY PROGRAM AND MANDATE 3401 02:15:07,200 --> 02:15:08,320 TO SUPPORT DISABILITY, HE 3402 02:15:08,320 --> 02:15:10,400 CANNABILITY AND WILL INCLUSION 3403 02:15:10,400 --> 02:15:12,840 AS OPPOSED TO CORRECTION, HOW 3404 02:15:12,840 --> 02:15:14,840 DOES THAT CHALLENGE US TO 3405 02:15:14,840 --> 02:15:17,040 THINK ABOUT OUR RESEARCH 3406 02:15:17,040 --> 02:15:23,800 AGENDA IN TERMS OF SUPPORTING 3407 02:15:23,800 --> 02:15:25,160 DISABILITY WITH REGARD TO 3408 02:15:25,160 --> 02:15:25,560 CORRECTIONS? 3409 02:15:25,560 --> 02:15:26,800 >>THAT IS A GREAT QUESTION 3410 02:15:26,800 --> 02:15:35,120 AND IT STARTS WITH WHO ARE WE 3411 02:15:35,120 --> 02:15:38,000 INCLUDING IN RESEARCH AND HOW 3412 02:15:38,000 --> 02:15:41,440 ARE WE ADDRESSING SOME OF THE 3413 02:15:41,440 --> 02:15:47,040 SUPPORTS LIKE VISUAL 3414 02:15:47,040 --> 02:15:49,080 IMPAIRMENTS, DETERIORATING 3415 02:15:49,080 --> 02:15:50,360 COGNITIVE AND VISUAL IMPAPERS 3416 02:15:50,360 --> 02:15:57,720 AND WITH HEARING IM-- 3417 02:15:57,720 --> 02:16:00,280 IMPAIRMENTS, AND WITH HEARING 3418 02:16:00,280 --> 02:16:01,880 IMPAIRMENTS, ARE WE EXCLUDING 3419 02:16:01,880 --> 02:16:04,600 THEM BECAUSE WE KNOW THEY 3420 02:16:04,600 --> 02:16:07,760 CAN'T PROVIDE INFORMED CONSENT 3421 02:16:07,760 --> 02:16:09,280 OR ARE WE REALLY NOT TRYING 3422 02:16:09,280 --> 02:16:10,480 HARD ENOUGH TO GET IT. 3423 02:16:10,480 --> 02:16:12,560 SO I THINK IT STARTED FROM OUR 3424 02:16:12,560 --> 02:16:13,960 CRITERIA AND THEN MOVED INTO 3425 02:16:13,960 --> 02:16:14,520 OUR APPROACH. 3426 02:16:14,520 --> 02:16:16,160 IF WE SCREEN FOR THESE THINGS 3427 02:16:16,160 --> 02:16:19,040 AND, YOU KNOW, WE CAN EASILY 3428 02:16:19,040 --> 02:16:20,240 PUT PATHWAYS IN TO ADDRESS 3429 02:16:20,240 --> 02:16:21,640 THEM, MORE PEOPLE WILL FEEL 3430 02:16:21,640 --> 02:16:23,560 LIKE THE RESEARCH IS 3431 02:16:23,560 --> 02:16:24,720 ADDRESSING THEIR CLEAR 3432 02:16:24,720 --> 02:16:25,520 CLINICAL NEEDS AND I THINK 3433 02:16:25,520 --> 02:16:26,800 THAT IS WHERE IT STARTS. 3434 02:16:26,800 --> 02:16:29,240 I DON'T WANT TO BE LABOR IT 3435 02:16:29,240 --> 02:16:31,160 AND I THINK A LOT OF OTHER 3436 02:16:31,160 --> 02:16:33,000 PEOPLE HAVE SOME OPINIONS HERE 3437 02:16:33,000 --> 02:16:35,000 BUT CERTAINLY THINK FROM A 3438 02:16:35,000 --> 02:16:36,440 RESEARCH STANDPOINT, THAT IS 3439 02:16:36,440 --> 02:16:39,880 WHERE IT STARTS, AT THE 3440 02:16:39,880 --> 02:16:47,920 BEGINNING. TO BRONWEN. 3441 02:16:47,920 --> 02:16:51,160 >>YES, THANK YOU, IT IS GREAT 3442 02:16:51,160 --> 02:16:53,240 THAT WE HAVE A ENVIRONMENT BUT 3443 02:16:53,240 --> 02:16:55,440 THE BEST THING TO DO IS MAKE 3444 02:16:55,440 --> 02:16:56,680 SURE THE PATIENT FEELS 3445 02:16:56,680 --> 02:17:03,720 CONFIDENT SO IF THEY END UP 3446 02:17:03,720 --> 02:17:06,360 NEEDING SOME DEVICE 3447 02:17:06,360 --> 02:17:08,680 ASSISTANCE, THAT THE SOCIETY 3448 02:17:08,680 --> 02:17:10,840 TO SCALE WILL FACILITATE THAT 3449 02:17:10,840 --> 02:17:12,680 FOR THEM AND ESPECIALLY WHEN 3450 02:17:12,680 --> 02:17:15,920 THEY START OUT DIFFERENT FROM 3451 02:17:15,920 --> 02:17:17,840 WHAT THEIR PRE-ICU STAY WAS. 3452 02:17:17,840 --> 02:17:20,560 SO COMING UP WITH A DEVICE 3453 02:17:20,560 --> 02:17:24,120 THAT YOU ARE INDEPENDENT ON 3454 02:17:24,120 --> 02:17:27,280 IMPACTS FROM A PSYCHOLOGICAL 3455 02:17:27,280 --> 02:17:28,640 STANDPOINT HOW YOU FEEL ABOUT 3456 02:17:28,640 --> 02:17:29,120 RECOVERY. 3457 02:17:29,120 --> 02:17:33,120 SO IT IS GREAT WE HAVE THE 3458 02:17:33,120 --> 02:17:36,640 ASSISTANCE BUT NEED TO 3459 02:17:36,640 --> 02:17:38,480 REMEMBER THAT AFFECTS THEIR 3460 02:17:38,480 --> 02:17:42,240 RECOVERY AS WELL AND THEN WITH 3461 02:17:42,240 --> 02:17:44,960 THE INCLUSIVE ENVIRONMENT, WE 3462 02:17:44,960 --> 02:17:47,160 CAN PUSH PEOPLE AS MUCH AS WE 3463 02:17:47,160 --> 02:17:48,840 CAN TO GET BACK TO THE LEVEL 3464 02:17:48,840 --> 02:17:51,160 THEY WOULD LIKE TO GET BACK TO 3465 02:17:51,160 --> 02:17:54,200 ESPECIALLY LEAVE IF THE 3466 02:17:54,200 --> 02:17:55,040 DISABILITY LOOKS DIFFERENT 3467 02:17:55,040 --> 02:17:57,240 THAN WHAT IT LOOKED LIKE 3468 02:17:57,240 --> 02:17:59,360 BEFORE SO PUTTING PATIENT 3469 02:17:59,360 --> 02:18:01,720 VALUES AND EXPECTATIONS IN 3470 02:18:01,720 --> 02:18:03,680 THERE INVOLVED WITH WHAT THEY 3471 02:18:03,680 --> 02:18:05,080 WOULD NORMALLY BE DOING AND 3472 02:18:05,080 --> 02:18:13,760 HOW WE TRACK THAT AND BOTH USE 3473 02:18:13,760 --> 02:18:15,480 THE ABILITY TO, SAY A PATIENT 3474 02:18:15,480 --> 02:18:20,200 TALKS WELL BUT TO USE A 3475 02:18:20,200 --> 02:18:21,160 DEVICE, DOESN'T MEAN YOU ARE 3476 02:18:21,160 --> 02:18:23,160 OFF THE SCALE FOR THAT. 3477 02:18:23,160 --> 02:18:26,080 BECAUSE SOMETIMES WE SEE A 3478 02:18:26,080 --> 02:18:27,360 WALKING STICK AND SAY WELL 3479 02:18:27,360 --> 02:18:30,000 THAT IS GREAT BUT IN SCORING 3480 02:18:30,000 --> 02:18:33,640 THESE THINGS, SOMEHOW IT MUST 3481 02:18:33,640 --> 02:18:37,800 BE APART FROM INDEPENDENT. 3482 02:18:37,800 --> 02:18:39,080 >>BR ONWEN, I WAS GOING TO 3483 02:18:39,080 --> 02:18:40,080 COMMENT LATER BUT I WANT TO 3484 02:18:40,080 --> 02:18:41,600 FOLLOW UP ON THIS VERY 3485 02:18:41,600 --> 02:18:43,240 IMPORTANT POINT OF YOURS. 3486 02:18:43,240 --> 02:18:47,920 EVEN WHEN WE'RE MEASURING 3487 02:18:47,920 --> 02:18:49,960 DISABILITY STUDIES, YOU ARE 3488 02:18:49,960 --> 02:18:51,800 STILL DEPENDENT ON ANOTHER 3489 02:18:51,800 --> 02:18:55,360 PERSON TO COMPLETE IT AND AN 3490 02:18:55,360 --> 02:18:57,920 ADAPTIVE DEVICES IS EXACTLY 3491 02:18:57,920 --> 02:19:00,080 THAT, THAT ALLOWS A PERSON TO 3492 02:19:00,080 --> 02:19:02,640 COMPLETE THE TASK AND NOT BE 3493 02:19:02,640 --> 02:19:03,240 DISABLED IN IT. 3494 02:19:03,240 --> 02:19:05,480 SOMETIMES THEY NEED TO USE IT 3495 02:19:05,480 --> 02:19:06,640 TEMPORARY OR SOMETIMES THEY 3496 02:19:06,640 --> 02:19:08,760 USE IT LONG-TERM BUT THE THING 3497 02:19:08,760 --> 02:19:10,920 IS IT ALLOWS THEM TO COMPLETE 3498 02:19:10,920 --> 02:19:12,000 THE TASK WHICH IS SO 3499 02:19:12,000 --> 02:19:12,360 IMPORTANT. 3500 02:19:12,360 --> 02:19:15,200 SO THERE IS A POSITIVE WAY TO 3501 02:19:15,200 --> 02:19:16,240 FRAME THOSE DEVICES AND 3502 02:19:16,240 --> 02:19:18,120 PATIENTS MAY HAVE TO 3503 02:19:18,120 --> 02:19:20,080 EMOTIONALLY ADAPT TO USING ONE 3504 02:19:20,080 --> 02:19:23,400 BUT SOMETIMES IT IS NOT JUST 3505 02:19:23,400 --> 02:19:26,480 FOR A MINUTE AND GET THE 3506 02:19:26,480 --> 02:19:28,280 PATIENTS TO VALUE. 3507 02:19:28,280 --> 02:19:32,840 SO JASON SAYS EXACTLY, 3508 02:19:32,840 --> 02:19:33,760 EMPHASIZING IN THE CHAT. 3509 02:19:33,760 --> 02:19:36,240 THANK YOU FOR THAT POINT 3510 02:19:36,240 --> 02:19:38,920 >>WHEN WE TALK ABOUT 3511 02:19:38,920 --> 02:19:39,720 ACCOMMODATION AND 3512 02:19:39,720 --> 02:19:41,360 ADAPTATION -- JACK, I AM 3513 02:19:41,360 --> 02:19:42,720 SORRY, I CUT YOU OFF. 3514 02:19:42,720 --> 02:19:44,360 I WILL BE REALLY QUICK. 3515 02:19:44,360 --> 02:19:46,480 THOSE ARE TASKS THAT OFTEN 3516 02:19:46,480 --> 02:19:47,920 EXIST IN THE REHABILITATION 3517 02:19:47,920 --> 02:19:49,880 ARENA AND I THINK AS A 3518 02:19:49,880 --> 02:19:53,400 REMINDER AS WE THINK ABOUT 3519 02:19:53,400 --> 02:19:56,800 PARADIGMS, WE NEED TO BE 3520 02:19:56,800 --> 02:20:01,160 THOUGHTFUL ABOUT INTRODUCING 3521 02:20:01,160 --> 02:20:05,280 EXPLICITLY REHABILITATIVE 3522 02:20:05,280 --> 02:20:10,360 APPARENTLY DIMES, PHYSICIANS, 3523 02:20:10,360 --> 02:20:11,120 OCCUPATIONAL THERAPISTS, 3524 02:20:11,120 --> 02:20:12,840 PEOPLE WHO AREN'T AT THE TABLE 3525 02:20:12,840 --> 02:20:14,040 AS MUCH AS WE WOULD LIKE THEM 3526 02:20:14,040 --> 02:20:15,440 TO BE IN REHAB. 3527 02:20:15,440 --> 02:20:17,280 YES, THE OTHER THING TO KEEP 3528 02:20:17,280 --> 02:20:19,280 IN MIND IS REBUILDING BRAINS 3529 02:20:19,280 --> 02:20:20,760 AND BODIES BUT THE OTHER THING 3530 02:20:20,760 --> 02:20:23,440 WE NEED TO GET BETTER AT IS 3531 02:20:23,440 --> 02:20:25,360 COMING ALONGSIDE PEOPLE SAYING 3532 02:20:25,360 --> 02:20:27,120 WE WANT THIS OUTCOME FOR YOU 3533 02:20:27,120 --> 02:20:30,120 BUT HOW CAN WE HELP YOU HAVE A 3534 02:20:30,120 --> 02:20:31,720 MEANINGFUL LIFE EVEN IF YOU 3535 02:20:31,720 --> 02:20:33,320 NEVER GET ANY BETTER? 3536 02:20:33,320 --> 02:20:35,600 EVEN IF YOUR COGNITIVE 3537 02:20:35,600 --> 02:20:36,880 IMPROVEMENT DOESN'T IMPROVE AS 3538 02:20:36,880 --> 02:20:40,040 ALL, HOW CAN WE HELP YOU LEAN 3539 02:20:40,040 --> 02:20:42,240 INTO YOUR VALUES AND PURSUE A 3540 02:20:42,240 --> 02:20:44,480 MEANINGFUL LIFE AND THAT IS AN 3541 02:20:44,480 --> 02:20:45,960 IMPORTANT OUTCOME. 3542 02:20:45,960 --> 02:20:48,840 IT IS NOT NECESSARILY A WIN, 3543 02:20:48,840 --> 02:20:50,400 REPACK BILLATION OR GO HOME, 3544 02:20:50,400 --> 02:20:53,120 IT IS HOW CAN WE HELP YOU HAVE 3545 02:20:53,120 --> 02:20:53,680 A MEANINGFUL WORK. 3546 02:20:53,680 --> 02:20:57,720 >>AND I THINK THERE IS A LOT 3547 02:20:57,720 --> 02:21:02,040 OF RESEARCH TO BE DONE CLEARLY 3548 02:21:02,040 --> 02:21:03,200 WITH A PSYCHOLOGICAL IMPACT ON 3549 02:21:03,200 --> 02:21:06,200 IT BUT WITHIN THE SOCIAL SIGNS 3550 02:21:06,200 --> 02:21:08,080 OF NIH, HOW WE DO THAT WELL 3551 02:21:08,080 --> 02:21:10,120 AND DEVELOP THOSE TECHNIQUES 3552 02:21:10,120 --> 02:21:11,600 RATHER THAN JUST ASSUME THAT 3553 02:21:11,600 --> 02:21:14,280 IS HOW THE WORLD DOES IT, IT 3554 02:21:14,280 --> 02:21:16,840 IS PROBABLY GOOD. 3555 02:21:16,840 --> 02:21:17,640 CARLA? 3556 02:21:17,640 --> 02:21:19,840 I KNOW ADAPTATION AND GETTING 3557 02:21:19,840 --> 02:21:21,720 INTO DEVICES IS A BREAD AND 3558 02:21:21,720 --> 02:21:24,640 BUTTER PART OF YOUR LOW 3559 02:21:24,640 --> 02:21:26,600 HANGING FRUIT. 3560 02:21:26,600 --> 02:21:27,200 THOUGHTS? 3561 02:21:27,200 --> 02:21:31,040 >>YEAH, I MEAN I WOULD ECHO 3562 02:21:31,040 --> 02:21:32,280 WHAT BRONWEN SAID. 3563 02:21:32,280 --> 02:21:33,920 ANY MARKER OF PHYSICAL 3564 02:21:33,920 --> 02:21:35,240 DISABILITY IS SOMETHING THEY 3565 02:21:35,240 --> 02:21:38,080 ARE AND YOU RESISTANT TO. 3566 02:21:38,080 --> 02:21:39,440 OXYGEN IS ONE WE HAVE A LOT 3567 02:21:39,440 --> 02:21:41,960 AND WE ALSO TRY TO FORM LATE 3568 02:21:41,960 --> 02:21:45,720 IT TO HOW CAN WE HELP YOU DO 3569 02:21:45,720 --> 02:21:46,600 MORE. 3570 02:21:46,600 --> 02:21:48,760 I WOULD PROBABLY USE LANCE 3571 02:21:48,760 --> 02:21:50,240 ARMSTRONG AS MY SPORTS ANALOGY 3572 02:21:50,240 --> 02:21:52,440 BUT THIS IS SOMETHING TO 3573 02:21:52,440 --> 02:21:53,600 AUGMENT YOUR PERFORMANCE AND 3574 02:21:53,600 --> 02:21:55,080 GET TO DO THE THINGS YOU WANT 3575 02:21:55,080 --> 02:21:59,240 TO DO IN A LEGAL WAY. 3576 02:21:59,240 --> 02:22:02,080 AND YOU KNOW SUPPORTING THAT 3577 02:22:02,080 --> 02:22:03,120 SENSIBILITY AND ADAPTABILITY 3578 02:22:03,120 --> 02:22:04,840 BUT ALSO GIVING THEM HOPE, 3579 02:22:04,840 --> 02:22:06,240 RIGHT, THAT THIS WILL CONTINUE 3580 02:22:06,240 --> 02:22:08,120 TO RECOVER WHERE SUCH HOPE IS 3581 02:22:08,120 --> 02:22:08,520 APPROPRIATE. 3582 02:22:08,520 --> 02:22:10,760 THAT IS WHERE I THINK SEEING A 3583 02:22:10,760 --> 02:22:12,720 LOT OF THESE PATIENTS IS VERY 3584 02:22:12,720 --> 02:22:15,800 BENEFICIAL IN TERMS OF 3585 02:22:15,800 --> 02:22:17,080 PROGNOSTICATING AND PREDICTING 3586 02:22:17,080 --> 02:22:18,480 A TRAJECTORY FOR THEM. 3587 02:22:18,480 --> 02:22:21,000 YOU KNOW OFTEN FOLKS WILL COME 3588 02:22:21,000 --> 02:22:24,640 IN ON OXYGEN, CAN'T WALK, 3589 02:22:24,640 --> 02:22:27,040 STILL USING A WALKER, LIKE 3590 02:22:27,040 --> 02:22:32,080 FOUR WEEKS OUT AND COMPLETELY 3591 02:22:32,080 --> 02:22:33,360 DERESPONDENT AND WE'RE LIKE 3592 02:22:33,360 --> 02:22:36,760 YOU ARE RIGHT AT THE BEGINNING 3593 02:22:36,760 --> 02:22:38,520 OF THIS RECOVERY TRAJECTORY 3594 02:22:38,520 --> 02:22:40,000 AND GIVING SOME TIME FRAME OF 3595 02:22:40,000 --> 02:22:41,600 WE ARE IN THE EVEN GOING TO 3596 02:22:41,600 --> 02:22:43,640 TALK ABOUT THIS FOR A YEAR OR 3597 02:22:43,640 --> 02:22:48,960 NOT EVEN SAY RETURN TO WORK 3598 02:22:48,960 --> 02:22:50,040 TILL XYZ HAPPENS. 3599 02:22:50,040 --> 02:22:51,200 SO FRAMING THAT ACCESSIBILITY, 3600 02:22:51,200 --> 02:22:54,080 THERE IS A COMMENT IN THE CHAT 3601 02:22:54,080 --> 02:22:56,880 ABOUT, YOU KNOW, PATIENTS WHO 3602 02:22:56,880 --> 02:22:58,040 ARE OFFERED FOLLOW UP AND 3603 02:22:58,040 --> 02:23:00,040 DON'T WANT TO TAKE IT, WE SEE 3604 02:23:00,040 --> 02:23:01,200 THAT ALL THE TIME. 3605 02:23:01,200 --> 02:23:03,160 THEY ARE LIKE I AM DONE, 3606 02:23:03,160 --> 02:23:04,680 CRITICAL ILLNESS IS DONE, 3607 02:23:04,680 --> 02:23:06,160 HOSPITAL WAS TERRIBLE, LET ME 3608 02:23:06,160 --> 02:23:08,320 LEAVE THAT IN THE REAR VIEW 3609 02:23:08,320 --> 02:23:10,720 AND THEY DECLINE TO 3610 02:23:10,720 --> 02:23:12,720 SCHEDULE -- OR WE HAD ONE 3611 02:23:12,720 --> 02:23:14,160 PATIENT DECLINE TO SCHEDULE 3612 02:23:14,160 --> 02:23:20,160 BECAUSE WE TOLD HIM PART OF 3613 02:23:20,160 --> 02:23:22,120 THE IT WAS A SIX MINUTE WALK 3614 02:23:22,120 --> 02:23:24,200 AND HIS WIFE IS LIKE HE HAVE 3615 02:23:24,200 --> 02:23:25,400 CAN'T WALK SIX MINUTES AND I 3616 02:23:25,400 --> 02:23:27,560 AM LIKE IT IS PART OF THE 3617 02:23:27,560 --> 02:23:32,240 TREATMENT AND YOU HAVE 46 3618 02:23:32,240 --> 02:23:34,560 GRANDCHILDREN SO PART OF THE 3619 02:23:34,560 --> 02:23:35,360 RECOVERY IS WALKING. 3620 02:23:35,360 --> 02:23:40,000 BUT WE HAVE PATIENTS WHO SAY 3621 02:23:40,000 --> 02:23:43,400 NO, WE DON'T WANT TO COME BACK 3622 02:23:43,400 --> 02:23:48,160 TO CLINIC, LIKE IF COGNITIVE 3623 02:23:48,160 --> 02:23:57,160 IMPAIRMENT IS ON THE TABLE, 3624 02:23:57,160 --> 02:23:58,640 GIVING THEIR FAMILIES THAT 3625 02:23:58,640 --> 02:23:59,800 INFORMATION TO CALL. 3626 02:23:59,800 --> 02:24:00,960 HAVING THE ACCESSIBILITY AND 3627 02:24:00,960 --> 02:24:02,680 HAVING CONVERSATIONS WITH 3628 02:24:02,680 --> 02:24:03,840 PATIENTS, WE'RE LEARNING MORE 3629 02:24:03,840 --> 02:24:06,840 AND MORE ABOUT WHAT THEY NEED 3630 02:24:06,840 --> 02:24:08,440 AND BEING ABLE TO COLLECT THAT 3631 02:24:08,440 --> 02:24:14,000 DATA IN A WAY THAT IS 3632 02:24:14,000 --> 02:24:16,120 DIGESTIBLE AND 3633 02:24:16,120 --> 02:24:19,360 DISSEMINATE-ABLE -- SORRY, NEW 3634 02:24:19,360 --> 02:24:21,320 WORD, THAT IS BEING 3635 02:24:21,320 --> 02:24:23,480 DISSEMINATED TO PEOPLE WHO 3636 02:24:23,480 --> 02:24:26,200 NEED TO SEE THESE PATIENTS WHO 3637 02:24:26,200 --> 02:24:29,920 WILL BE N MR, PRIMARY CARE, 3638 02:24:29,920 --> 02:24:30,760 ICU FOLKS, GETTING THAT 3639 02:24:30,760 --> 02:24:32,800 KNOWLEDGE OUT IN THE PUBLIC 3640 02:24:32,800 --> 02:24:33,160 DOMAIN. 3641 02:24:33,160 --> 02:24:34,000 >>ALL RIGHT, WE WILL THROW 3642 02:24:34,000 --> 02:24:36,520 THE REST OF MY PLAN OUT AND 3643 02:24:36,520 --> 02:24:40,600 END WITH LIGHTNING ROUND, JUST 3644 02:24:40,600 --> 02:24:42,800 LIKE IN FRIENDS WHICH WE USED 3645 02:24:42,800 --> 02:24:45,440 TO BE ABLE TO WATCH, RIGHT, IS 3646 02:24:45,440 --> 02:24:46,120 SHORT ANSWERS. 3647 02:24:46,120 --> 02:24:49,080 SO I WILL PROPOSE THERE ARE AT 3648 02:24:49,080 --> 02:24:51,600 LEAST 30 BIOLOGISTS ON THIS 3649 02:24:51,600 --> 02:24:54,840 CALL SAYING GEE BEING A POST 3650 02:24:54,840 --> 02:24:56,440 ICU CLINICIAN IS REALLY HARD, 3651 02:24:56,440 --> 02:24:58,400 GLAD YOU ARE DOING IT, HOW DO 3652 02:24:58,400 --> 02:25:00,880 I HELP. 3653 02:25:00,880 --> 02:25:02,720 SO THE QUESTION IN THE ORDER 3654 02:25:02,720 --> 02:25:04,680 YOU CAME, WHAT IS A QUESTION 3655 02:25:04,680 --> 02:25:07,840 YOU REALLY WISH SOMEONE 3656 02:25:07,840 --> 02:25:11,400 FUNCTIONING MORE AT THE BASIC 3657 02:25:11,400 --> 02:25:14,560 BIOLOGY LEVEL COULD ANSWER OR 3658 02:25:14,560 --> 02:25:20,280 THE QUESTION YOU WISH YOU KNEW 3659 02:25:20,280 --> 02:25:20,920 THE ANSWER TO. 3660 02:25:20,920 --> 02:25:22,760 SO THIS IS TO PROMOTE 3661 02:25:22,760 --> 02:25:24,200 CONVERSATION AND WE WILL CALL 3662 02:25:24,200 --> 02:25:26,760 ON LAUREN AT THE END TO CLOSE 3663 02:25:26,760 --> 02:25:29,080 US OUT. 3664 02:25:29,080 --> 02:25:29,960 SO CARLA, GO. 3665 02:25:29,960 --> 02:25:30,920 >>SO HARD. 3666 02:25:30,920 --> 02:25:32,560 BUT SINCE WE'RE TALKING ABOUT 3667 02:25:32,560 --> 02:25:34,160 MUSCLE, I WILL SAY IF WE HAD 3668 02:25:34,160 --> 02:25:40,200 SOME KIND OF MARKER, BIOMARKER 3669 02:25:40,200 --> 02:25:41,400 OBJECTIVE CLINICALLY 3670 02:25:41,400 --> 02:25:42,520 AVAILABLE, MUSCLE STRENGTH 3671 02:25:42,520 --> 02:25:44,600 TOOL THAT PERHAPS COULD 3672 02:25:44,600 --> 02:25:46,960 PREDICT RECOVERY THAT WE COULD 3673 02:25:46,960 --> 02:25:52,840 TRACK FOR PATIENTS AND SHOW 3674 02:25:52,840 --> 02:25:54,240 THEM TO OUTLINE THEIR DEFICITS 3675 02:25:54,240 --> 02:25:55,960 AND THOUGH THEM TO GET BETTER, 3676 02:25:55,960 --> 02:25:59,440 THAT WOULD BE FANTASTIC. 3677 02:25:59,440 --> 02:26:01,800 SIDE NOTE, IT IS A JOY TO SEE 3678 02:26:01,800 --> 02:26:05,880 THESE PATIENTS IN CLINICS. 3679 02:26:05,880 --> 02:26:08,080 IF MY PATIENT SURVIVES THE 3680 02:26:08,080 --> 02:26:10,120 ICU, I LIKE FOR GO IN BETTER 3681 02:26:10,120 --> 02:26:12,200 TO SEE THEM IN CLINIC. 3682 02:26:12,200 --> 02:26:12,600 >>JIM? 3683 02:26:12,600 --> 02:26:15,680 >>I AM NOT A BIOLOGIST, NOT, 3684 02:26:15,680 --> 02:26:17,640 NOT, NOT, BUT I AM INTERESTED 3685 02:26:17,640 --> 02:26:18,120 IN THIS QUESTION. 3686 02:26:18,120 --> 02:26:20,280 THERE ARE A LOT OF PEOPLE, 3687 02:26:20,280 --> 02:26:22,560 MOST PEOPLE WHO ARE NOT 3688 02:26:22,560 --> 02:26:23,960 COGNITIVELY IMPAIRED WHEN THEY 3689 02:26:23,960 --> 02:26:25,480 LEAVE THE ICU AND THERE ARE 3690 02:26:25,480 --> 02:26:27,240 SOME PEOPLE WHO THRIVE AFTER 3691 02:26:27,240 --> 02:26:32,520 LONG STAYS ON THE VENTILATOR, 3692 02:26:32,520 --> 02:26:33,080 DELERIUM, ET CETERA. 3693 02:26:33,080 --> 02:26:34,680 I AM INTERESTED IN WHAT IS 3694 02:26:34,680 --> 02:26:36,520 HAPPENING IN THE BRAINS OF 3695 02:26:36,520 --> 02:26:37,960 PEOPLE WHO ARE DOING BETTER 3696 02:26:37,960 --> 02:26:40,640 THAN WE THINK THEY SHOULD BE 3697 02:26:40,640 --> 02:26:41,120 DOING. 3698 02:26:41,120 --> 02:26:44,400 >>SO HOW DO WE DESCRIBE SUPER 3699 02:26:44,400 --> 02:26:47,800 SURVIVORS, LOVE IT. 3700 02:26:47,800 --> 02:26:48,120 BRONWEN? 3701 02:26:48,120 --> 02:26:50,440 >>THE ONE THING WE SHOULD BE 3702 02:26:50,440 --> 02:26:52,640 DOING THAT TELLS US EVERYTHING 3703 02:26:52,640 --> 02:26:54,240 NOBLY FOR PATIENTS. 3704 02:26:54,240 --> 02:26:57,280 SO WHAT MUSCLE CAN I TEST THAT 3705 02:26:57,280 --> 02:27:03,400 WILL ALLOW THAT TO OPEN FOR 3706 02:27:03,400 --> 02:27:03,880 ME. 3707 02:27:03,880 --> 02:27:07,120 >>IT SEEMS LIKE YOU HAVE THE 3708 02:27:07,120 --> 02:27:08,200 GAUGE FOR -- 3709 02:27:08,200 --> 02:27:11,160 >>NO, BUT THAT IS A CLUE FOR 3710 02:27:11,160 --> 02:27:14,520 ME, LIKE WHAT MUSCLE THAT HAS 3711 02:27:14,520 --> 02:27:15,800 PARTICULAR MUSCLE FIBERS AND 3712 02:27:15,800 --> 02:27:17,440 THAT GIVES ME THE GLOBAL 3713 02:27:17,440 --> 02:27:19,800 ANSWER IN TERMS OF OTHER 3714 02:27:19,800 --> 02:27:21,920 MEASURES TO MEASURE OR OTHER 3715 02:27:21,920 --> 02:27:23,440 MUSCLE GROUPS AS WELL. 3716 02:27:23,440 --> 02:27:30,480 SO THAT IS WHAT I WOULD ASK 3717 02:27:30,480 --> 02:27:32,960 ABOUT. 3718 02:27:32,960 --> 02:27:33,960 >>AWESOME, Dr. FALVEY? 3719 02:27:33,960 --> 02:27:36,240 >>I WOULD ASK ABOUT 3720 02:27:36,240 --> 02:27:39,320 RESILIENCE AND HOW DOES 3721 02:27:39,320 --> 02:27:43,320 SOCIALABILITY ALTER THAT FROM 3722 02:27:43,320 --> 02:27:45,840 A BIOLOGICAL STANDPOINT. 3723 02:27:45,840 --> 02:27:47,560 >>Dr. FERRANTE, YOU WANT TO 3724 02:27:47,560 --> 02:27:49,120 ANSWER THE QUESTION AND TAKE 3725 02:27:49,120 --> 02:27:50,280 US OUT? 3726 02:27:50,280 --> 02:27:52,600 >>YES, AS OTHER SPEAKERS WERE 3727 02:27:52,600 --> 02:27:54,720 CHIMING IN, I WAS THINKING 3728 02:27:54,720 --> 02:27:56,120 ABOUT RESILIENCE AND 3729 02:27:56,120 --> 02:27:59,640 PARTICULARLY PATIENTS WHO HAVE 3730 02:27:59,640 --> 02:28:00,320 ESCAPED FUNCTIONAL RECOVERY 3731 02:28:00,320 --> 02:28:02,480 AND CONTINUE TO HAVE 3732 02:28:02,480 --> 02:28:03,680 IMPAIRMENT SO MY SPECIFIC ASK 3733 02:28:03,680 --> 02:28:06,760 WOULD BE A BIOMILE -PER-HOURER 3734 02:28:06,760 --> 02:28:08,480 OF COGNITIVE RESILIENCE OR 3735 02:28:08,480 --> 02:28:11,040 SOME SORT OF BIOMARKER 3736 02:28:11,040 --> 02:28:13,440 FOCUSING MORE ON THE COGNITIVE 3737 02:28:13,440 --> 02:28:15,360 ASPECTS MEASURED ACROSS THE 3738 02:28:15,360 --> 02:28:16,880 CRITICAL ELEMENTS. 3739 02:28:16,880 --> 02:28:19,400 >>I STARTED THE CONVERSATION 3740 02:28:19,400 --> 02:28:22,480 ABOUT RESILIENCE WHICH WE HAVE 3741 02:28:22,480 --> 02:28:25,800 NOT DEALT WITH IN THESE TALKS, 3742 02:28:25,800 --> 02:28:28,000 A MORE COGNITIVE SPACE, WHO 3743 02:28:28,000 --> 02:28:31,840 ARE THE PEOPLE WHO SHOULD BE 3744 02:28:31,840 --> 02:28:33,360 CONSULTING WITH AS STAFF ARE 3745 02:28:33,360 --> 02:28:35,040 THE QUESTION AND WITH THAT HE 3746 02:28:35,040 --> 02:28:37,760 WILL TURN OVER TO TERRI AND 3747 02:28:37,760 --> 02:28:42,080 TIM BECAUSE I THINK WE ARE AT 3748 02:28:42,080 --> 02:28:43,440 OUR LUNCH BREAK. 3749 02:28:43,440 --> 02:28:45,000 >>WHINING WE HAVE 30 SECONDS 3750 02:28:45,000 --> 02:28:48,600 IN OUR LIGHTNING ROUND FOR 3751 02:28:48,600 --> 02:28:50,800 Dr. IWASHYNA TO ANSWER HIS 3752 02:28:50,800 --> 02:28:51,720 OWN QUESTION. 3753 02:28:51,720 --> 02:28:52,080 [LAUGHTER] 3754 02:28:52,080 --> 02:28:54,560 >>OH, I FEEL LIKE WE ACTUALLY 3755 02:28:54,560 --> 02:28:58,800 KNOW THAT FROM ANIMAL MODEL OF 3756 02:28:58,800 --> 02:29:00,240 SOCIALABILITY ARE INCREDIBLY 3757 02:29:00,240 --> 02:29:01,560 IMPORTANT AND THAT 3758 02:29:01,560 --> 02:29:05,640 FOUNDATIONALLY, IF YOU LEAVE A 3759 02:29:05,640 --> 02:29:07,000 RAT ALONE, IT WILL NOT DO WELL 3760 02:29:07,000 --> 02:29:09,760 AND WILL YOU KEEP IT IN A 3761 02:29:09,760 --> 02:29:12,400 COLONY, IT DOES IT BETTER AND 3762 02:29:12,400 --> 02:29:15,760 HOW THE PRESENCE OF OTHER 3763 02:29:15,760 --> 02:29:18,320 ANIMALS HELP OR DOESN'T HELP 3764 02:29:18,320 --> 02:29:19,440 RECOVERY FUNCTION ARREST 3765 02:29:19,440 --> 02:29:19,720 WARDS. 3766 02:29:19,720 --> 02:29:21,160 I THINK IT IS IMPORTANT TO 3767 02:29:21,160 --> 02:29:23,840 HAVE YOUR SPOUSE AT THE 3768 02:29:23,840 --> 02:29:24,160 BEDSIDE. 3769 02:29:24,160 --> 02:29:24,840 >> TERRIFIC, I DON'T THINK 3770 02:29:24,840 --> 02:29:26,880 ANYONE IS GOING TO ARGUE WITH 3771 02:29:26,880 --> 02:29:27,960 THAT POINT. 3772 02:29:27,960 --> 02:29:29,560 WHAT AN INCREDIBLE KICKOFF FOR 3773 02:29:29,560 --> 02:29:30,280 A DAY. 3774 02:29:30,280 --> 02:29:32,600 THAT SESSION WAS ABSOLUTELY 3775 02:29:32,600 --> 02:29:33,000 INCREDIBLE. 3776 02:29:33,000 --> 02:29:35,080 THANK YOU IS A MUCH FOR THE 3777 02:29:35,080 --> 02:29:36,400 FANTASTIC QUESTIONS IN THE 3778 02:29:36,400 --> 02:29:37,320 CHAT AND REALLY RICH 3779 02:29:37,320 --> 02:29:37,720 DISCUSSION. 3780 02:29:37,720 --> 02:29:40,080 I THINK WE GET A 15-MINUTE 3781 02:29:40,080 --> 02:29:42,240 BREAK SO PLEASE SAY HELLO TO 3782 02:29:42,240 --> 02:29:43,440 YOUR SPOUSE IF YOU ARE HOME 3783 02:29:43,440 --> 02:29:45,520 AND BENT A CUP OF TEA AND WE 3784 02:29:45,520 --> 02:29:48,040 WILL SEE YOU ALL BACK AT A 3785 02:29:48,040 --> 02:29:49,280 QUARTER TO THE HOUR. 3786 02:29:49,280 --> 02:29:52,080 THANK YOU SO MUCH. 3787 02:29:52,080 --> 02:29:54,200 WE ARE JUMP BACK IN WITH SESSION 3788 02:29:54,200 --> 02:29:55,840 2, HOPEFULLY EVERYBODY MADE GOOD 3789 02:29:55,840 --> 02:29:57,640 USE OF THAT LONG LUNCH BREAK 3790 02:29:57,640 --> 02:30:02,000 THAT WE BUILT INTO THE DAY. 3791 02:30:02,000 --> 02:30:03,480 SESSION 2 FOCUSES ON 3792 02:30:03,480 --> 02:30:05,720 PATHOGENESIS AND RECOVERY OF 3793 02:30:05,720 --> 02:30:06,560 NEUROCOGNITIVE DYSFUNCTION IN 3794 02:30:06,560 --> 02:30:07,960 ARDS SURVIVORS. I WILL 3795 02:30:07,960 --> 02:30:09,600 INTRODUCE THE MODERATOR WHOSE 3796 02:30:09,600 --> 02:30:12,760 WILL INTRODUCE THE SESSION 3797 02:30:12,760 --> 02:30:15,760 SPEAKERS. JOE IS A PHYSICIAN AND 3798 02:30:15,760 --> 02:30:17,240 PROFESSOR MEDICINE UNIVERSITY OF 3799 02:30:17,240 --> 02:30:18,440 COLORADO HE STUDIES THE 3800 02:30:18,440 --> 02:30:20,360 COGNITIVE CONSEQUENCES OF SEPSIS 3801 02:30:20,360 --> 02:30:22,080 AND CRITICAL ILLNESS. AND 3802 02:30:22,080 --> 02:30:25,480 SPECIFICALLY FOCUSES ON USING 3803 02:30:25,480 --> 02:30:27,440 BASIC TRANSLATIONAL RESEARCH TO 3804 02:30:27,440 --> 02:30:30,480 IDENTIFY THE RELEVANCE OF BRAIN 3805 02:30:30,480 --> 02:30:32,960 PENETRATING HEPARIN SULFATE AND 3806 02:30:32,960 --> 02:30:34,760 CHONDROITIN SULFATE. BEN SINGER 3807 02:30:34,760 --> 02:30:39,920 IS A PHYSICIAN AND PROFESSOR 3808 02:30:39,920 --> 02:30:40,760 UNIVERSITY OF MICHIGAN WHERE HE 3809 02:30:40,760 --> 02:30:45,200 IS A NEUROSCIENTIST AND FOCUSES 3810 02:30:45,200 --> 02:30:47,160 ON BOTH INPATIENT AND OUTPATIENT 3811 02:30:47,160 --> 02:30:49,440 CARE FOR PATIENTS WITH CHRONIC 3812 02:30:49,440 --> 02:30:51,240 RESPIRATORY FAILURE REQUIRING 3813 02:30:51,240 --> 02:30:53,440 INVASIVE -- NON-INVASIVE 3814 02:30:53,440 --> 02:30:55,720 VENTILATORY SUPPORT. HIS LAB 3815 02:30:55,720 --> 02:30:57,160 FOCUSES ON COVERING MECHANISMS 3816 02:30:57,160 --> 02:30:59,040 OF CHRONIC BRAIN DYSFUNCTION AND 3817 02:30:59,040 --> 02:31:00,840 INJURY AND SURVIVORS OF CRITICAL 3818 02:31:00,840 --> 02:31:02,160 ILLNESS USING MOUSE MODELS 3819 02:31:02,160 --> 02:31:05,000 SEPSIS AND PNEUMONIA. THANKS SO 3820 02:31:05,000 --> 02:31:06,160 MUCH FOR MODERATING JOE AND BEN, 3821 02:31:06,160 --> 02:31:07,200 TAKE IT AWAY. 3822 02:31:07,200 --> 02:31:09,760 >> THANKS SO MUCH FOR THAT 3823 02:31:09,760 --> 02:31:11,680 INTRODUCTION. REALLY EXCITED FOR 3824 02:31:11,680 --> 02:31:13,880 THIS PART OF THE SYMPOSIUM. I 3825 02:31:13,880 --> 02:31:15,080 WANT TO SAY FIRST THANK YOU FOR 3826 02:31:15,080 --> 02:31:16,600 ALL THOSE WHO ARE ATTENDING AND 3827 02:31:16,600 --> 02:31:18,040 BE SO ENGAGED I HOPE YOU 3828 02:31:18,040 --> 02:31:20,040 CONTINUE TO DO SO. PLEASE FEEL 3829 02:31:20,040 --> 02:31:22,360 FREE TO THROW A QUESTION INTO 3830 02:31:22,360 --> 02:31:24,040 CHAT AS YOU HAVE BEEN DOING WITH 3831 02:31:24,040 --> 02:31:25,960 GREAT SUCCESS. WE WILL ASK THOSE 3832 02:31:25,960 --> 02:31:27,480 QUESTIONS TO THE BEST OF OURANT 3833 02:31:27,480 --> 02:31:29,720 THROUGHOUT THE TALKS. WE HAVE A 3834 02:31:29,720 --> 02:31:31,480 TALL ORDER TO FOLLOW THE FIRST 3835 02:31:31,480 --> 02:31:33,040 SESSION I HAVE TO SAY. WHY ARE 3836 02:31:33,040 --> 02:31:34,960 THERE SUPER SURVIVORS OF ARDS 3837 02:31:34,960 --> 02:31:37,160 AND HOPEFULLY WE CAN PROVIDE 3838 02:31:37,160 --> 02:31:40,200 REALLY NICE INSIGHT INTO THIS 3839 02:31:40,200 --> 02:31:41,320 QUESTION. WE HAVE A DIVERSE SET 3840 02:31:41,320 --> 02:31:42,800 OF SPEAKERS THAT COME FROM THE 3841 02:31:42,800 --> 02:31:44,360 NEUROSCIENCE SIDE OF THINGS, THE 3842 02:31:44,360 --> 02:31:46,680 LUNG BIOLOGY SIDE OF THING AND 3843 02:31:46,680 --> 02:31:48,600 ALL PLACES IN BETWEEN SO REALLY 3844 02:31:48,600 --> 02:31:50,160 EXCITED TO BE ABLE TO SHARE 3845 02:31:50,160 --> 02:31:51,960 THEIR IDEAS WITH YOU TODAY. 3846 02:31:51,960 --> 02:31:53,160 AGAIN, REMINDER JUST FEEL FREE 3847 02:31:53,160 --> 02:31:55,320 TO THROW QUESTIONS INTO THE 3848 02:31:55,320 --> 02:31:56,680 CHAT. ALSO REMIND EVERYBODY IN 3849 02:31:56,680 --> 02:31:58,480 CASE YOU COME AFTER THE FIRST 3850 02:31:58,480 --> 02:31:59,640 SESSION THAT THE CHAT WILL BE 3851 02:31:59,640 --> 02:32:02,280 CAPTURED AT THE END AND WILL BE 3852 02:32:02,280 --> 02:32:04,200 PUBLICLY AVAILABLE SO AS JACK 3853 02:32:04,200 --> 02:32:07,360 MENTIONED, BE AS COURTEOUS AS 3854 02:32:07,360 --> 02:32:08,920 YOU CAN BE, SURE EVERYBODY WILL 3855 02:32:08,920 --> 02:32:10,200 BE AND EXTRAORDINARILY 3856 02:32:10,200 --> 02:32:11,440 PROFESSIONAL. WITH THAT I WANT 3857 02:32:11,440 --> 02:32:13,280 TO INTRODUCE OUR FIRST SPEAKER 3858 02:32:13,280 --> 02:32:15,600 AND IT IS AN ABSOLUTE PLEASURE 3859 02:32:15,600 --> 02:32:17,080 TO BE INTRODUCING HER TODAY. HER 3860 02:32:17,080 --> 02:32:19,200 NAME IS MICHELLE MONJE, SHE IS 3861 02:32:19,200 --> 02:32:22,840 AN M.D. Ph.D. AT STANFORD 3862 02:32:22,840 --> 02:32:24,920 UNIVERSITY. SHE IS PROFESSOR 3863 02:32:24,920 --> 02:32:26,440 NEUROLOGY AND NEUROLOGICAL 3864 02:32:26,440 --> 02:32:27,880 SCIENCES AND HOWARD HUGHES 3865 02:32:27,880 --> 02:32:29,040 MEDICAL INSTITUTE INVESTIGATOR, 3866 02:32:29,040 --> 02:32:32,280 SO A TRUE PLEASURE. SHE IS A 3867 02:32:32,280 --> 02:32:33,720 NEUROSCIENTIST I THINK BY 3868 02:32:33,720 --> 02:32:34,520 BACKGROUND, SHE WILL TALK MORE 3869 02:32:34,520 --> 02:32:36,880 TO THAT IN HER TALK TODAY. AND 3870 02:32:36,880 --> 02:32:39,080 SHE'S HAD A LOT OF RECOGNITION 3871 02:32:39,080 --> 02:32:41,440 HAVING RECEIVED NUMEROUS AWARDS 3872 02:32:41,440 --> 02:32:43,280 INCLUDING NIH DIRECTORS PIONEER 3873 02:32:43,280 --> 02:32:45,320 AWARD, MCARTHUR FELLOWSHIP AND 3874 02:32:45,320 --> 02:32:46,720 ELECTED TO THE NATIONAL ACADEMY 3875 02:32:46,720 --> 02:32:50,400 OF MEDICINE. THIS YEAR RECEIVED 3876 02:32:50,400 --> 02:32:52,880 A RICHARD LUNGSBURY AWARD 3877 02:32:52,880 --> 02:32:54,680 NATIONAL ACADEMY OF SCIENCES. 3878 02:32:54,680 --> 02:32:55,680 WITH THAT PASS TO MY SHE WOULD 3879 02:32:55,680 --> 02:32:57,360 TO CONTINUE THIS DISCUSSION. 3880 02:32:57,360 --> 02:32:59,200 >> WONDERFUL. THANK YOU SO MUCH 3881 02:32:59,200 --> 02:33:00,720 FOR THAT WONDERFUL INTRODUCTION. 3882 02:33:00,720 --> 02:33:02,600 THANK YOU SO MUCH FOR HAVING A 3883 02:33:02,600 --> 02:33:04,840 NEURAL ONCOLOGIST JOIN THIS 3884 02:33:04,840 --> 02:33:06,000 INCREDIBLY INTERESTING AND 3885 02:33:06,000 --> 02:33:07,800 ENGAGING DISCUSSION TODAY. I 3886 02:33:07,800 --> 02:33:09,640 WANTED TO TAKE EVERYONE A LITTLE 3887 02:33:09,640 --> 02:33:12,080 BIT THROUGH MY HONE SCIENTIFIC 3888 02:33:12,080 --> 02:33:14,680 JOURNEY AS A NEURAL ONCOLOGIST 3889 02:33:14,680 --> 02:33:16,200 AND CANCER THERAPY RELATED 3890 02:33:16,200 --> 02:33:17,960 COGNITIVE IMPAIRMENT AND HOW 3891 02:33:17,960 --> 02:33:20,640 THAT LED ME TO STUDY COGNITIVE 3892 02:33:20,640 --> 02:33:24,200 IMPAIRMENT AFTER LUNG INFECTION 3893 02:33:24,200 --> 02:33:26,680 THESE ARE MY DISCLOSURES. BY 3894 02:33:26,680 --> 02:33:28,640 TRAINING AND PACK IT IS I'M A 3895 02:33:28,640 --> 02:33:29,400 NEUROSCIENTIST AND AS MANY 3896 02:33:29,400 --> 02:33:30,920 PEOPLE IN THIS AUDIENCE 3897 02:33:30,920 --> 02:33:32,240 APPRECIATE HEALTHY COGNITIVE 3898 02:33:32,240 --> 02:33:34,920 FUNCTION DEPENDS UPON INTACT 3899 02:33:34,920 --> 02:33:36,880 MECHANISMS OF NEURAL HOMEOSTASIS 3900 02:33:36,880 --> 02:33:39,240 AND PLASTICITY. THAT INCLUDES IN 3901 02:33:39,240 --> 02:33:41,520 ORDER FOR THESE NICE ORANGE 3902 02:33:41,520 --> 02:33:43,200 NEURONS TO COMMUNICATE WITH EACH 3903 02:33:43,200 --> 02:33:45,480 OTHER ESTABLISHING SYNAPSES, 3904 02:33:45,480 --> 02:33:48,560 HAVING THAT CONNECTIVITY OF 3905 02:33:48,560 --> 02:33:50,280 APPROPRIATELY PRUNED AND 3906 02:33:50,280 --> 02:33:53,480 CONNECTED. AND BOTH OF THOSE 3907 02:33:53,480 --> 02:33:56,360 FUNCTIONS ARE REALLY ENABLED 3908 02:33:56,360 --> 02:33:58,360 LIKE GLIAL CELLS, ASTROCYTES 3909 02:33:58,360 --> 02:34:01,320 ENABLE FORMATION AND FUNCTION OF 3910 02:34:01,320 --> 02:34:02,560 SYNAPSES MICROGLIA AND 3911 02:34:02,560 --> 02:34:04,320 ASTROCYTES PRUNED SO THE 3912 02:34:04,320 --> 02:34:06,440 CONNECTIONS ARE WELL TRIMMED AND 3913 02:34:06,440 --> 02:34:08,880 APPROPRIATE FOR THAT CIRCUIT. 3914 02:34:08,880 --> 02:34:09,440 THEN TESTIMONY SPEED NEURAL 3915 02:34:09,440 --> 02:34:10,520 IMPULSE CONDUCTION IS REALLY 3916 02:34:10,520 --> 02:34:12,600 IMPORTANTLY MODULATED BY THE 3917 02:34:12,600 --> 02:34:15,040 FUNCTION OF OLIGODENDROCYTES 3918 02:34:15,040 --> 02:34:17,880 WHICH ARE GENERATED BY 3919 02:34:17,880 --> 02:34:19,680 OLIGODENDROCYTE PRECURSOR CELLS. 3920 02:34:19,680 --> 02:34:21,080 MYELINATION IS IMPORTANT NOT 3921 02:34:21,080 --> 02:34:23,680 JUST FOR SPEED OF INFLAMMATION 3922 02:34:23,680 --> 02:34:24,640 INFORMATION PROCESSING AND 3923 02:34:24,640 --> 02:34:27,320 SIGNALS DERIVED IN A SYNCHRONOUS 3924 02:34:27,320 --> 02:34:29,640 AND COORDINATED WAY. IT IS VERY 3925 02:34:29,640 --> 02:34:32,360 IMPORTANT FOR COGNITION 3926 02:34:32,360 --> 02:34:33,480 HOMEOSTASIS OF MYELIN AND PALACE 3927 02:34:33,480 --> 02:34:39,640 AT THIS THE PLASTICITY ADAPTIVE 3928 02:34:39,640 --> 02:34:40,600 CHANGES. ANOTHER IMPORTANT 3929 02:34:40,600 --> 02:34:41,800 CONTRIBUTION OF NEURAL 3930 02:34:41,800 --> 02:34:42,720 PLASTICITY THROUGHOUT THE LIFE 3931 02:34:42,720 --> 02:34:45,280 SPAN IS SOME DEGREE OF NEW 3932 02:34:45,280 --> 02:34:46,280 NEURON PRODUCTION IN MEMORY 3933 02:34:46,280 --> 02:34:47,600 CENTERED CALLED THE HIPPOCAMPUS 3934 02:34:47,600 --> 02:34:50,000 SO THIS PROCESS OF NEW NEURON 3935 02:34:50,000 --> 02:34:53,480 PRODUCTION OR NEUROGENESIS IS AN 3936 02:34:53,480 --> 02:34:54,800 ONGOING MECHANISM OF PLASTICITY 3937 02:34:54,800 --> 02:34:56,040 THAT CONTRIBUTES TO SOME FORMS 3938 02:34:56,040 --> 02:34:57,600 OF MEMORY FUNCTION. WHAT WE FIND 3939 02:34:57,600 --> 02:34:59,560 IS THAT EACH OF THESE MECHANISMS 3940 02:34:59,560 --> 02:35:02,600 OF PLASTICITY AND HOMEOSTASIS 3941 02:35:02,600 --> 02:35:05,200 CAN BE PROFOUNDLY AFFECTED AFTER 3942 02:35:05,200 --> 02:35:07,200 CANCER THERAPIES AND AS I HOPE I 3943 02:35:07,200 --> 02:35:09,520 CAN CONVINCE YOU IN MY 15 3944 02:35:09,520 --> 02:35:10,800 MINUTES AFTER A RANGE OF IMMUNE 3945 02:35:10,800 --> 02:35:14,560 CHALLENGES. I WOULD LIKE TO 3946 02:35:14,560 --> 02:35:17,160 FOCUS TO SOME DEGREE ON 3947 02:35:17,160 --> 02:35:18,000 UNDERSTAND UNDERSTANDING 3948 02:35:18,000 --> 02:35:19,640 ESPECIALLY THE WAY THAT CANCER 3949 02:35:19,640 --> 02:35:21,280 THERAPIES AND OTHER IMMUNE 3950 02:35:21,280 --> 02:35:23,320 CHALLENGES DISREGULATE THIS 3951 02:35:23,320 --> 02:35:25,000 PROCESS BY WHICH MYELIN 3952 02:35:25,000 --> 02:35:27,680 HOMEOSTASIS AND PLASTICITY 3953 02:35:27,680 --> 02:35:28,680 COORDINATE CIRCUIT FUNCTIONS 3954 02:35:28,680 --> 02:35:32,000 RELATIVE TO COGNITION. SO CANCER 3955 02:35:32,000 --> 02:35:33,960 THERAPY RELATED COGNITIVE 3956 02:35:33,960 --> 02:35:35,800 IMPAIRMENT ALSO SOMETIMES 3957 02:35:35,800 --> 02:35:37,840 COLLOQUIALLY CALLED CHEMO FOG, 3958 02:35:37,840 --> 02:35:39,360 IS A SYNDROME THAT SOUNDS 3959 02:35:39,360 --> 02:35:41,560 FAMILIAR TO MANY BECAUSE IT IS 3960 02:35:41,560 --> 02:35:43,000 VERY SIMILAR AS WELL POST 3961 02:35:43,000 --> 02:35:44,600 INTENSIVE CARE SYNDROME. IT IS 3962 02:35:44,600 --> 02:35:46,800 CHARACTERIZED BY IMPAIRED 3963 02:35:46,800 --> 02:35:49,800 ATTENTION, SCONATION, MEMORY, 3964 02:35:49,800 --> 02:35:50,440 COHEN CENTRATION MEMORY SPEED OF 3965 02:35:50,440 --> 02:35:51,640 INFORMATION PROCESSING 3966 02:35:51,640 --> 02:35:52,640 MULTI-TASKING AND COGNITIVE 3967 02:35:52,640 --> 02:35:55,000 FATIGUE. IN MANY CASES STANDARD 3968 02:35:55,000 --> 02:35:56,880 NEUROIMAGE IMAGING IS 3969 02:35:56,880 --> 02:35:59,880 UNREMARKABLE BUT MORE ADVANCE 3970 02:35:59,880 --> 02:36:01,240 IMAGING REVEALS SUBTLE WHITE 3971 02:36:01,240 --> 02:36:05,040 MATTER AND DECREASED HIPPOCAMPAL 3972 02:36:05,040 --> 02:36:06,800 VOLUMES. -AFFECTS CANCER 3973 02:36:06,800 --> 02:36:08,400 SURVIVORS TO EXTEND AND OVER 20 3974 02:36:08,400 --> 02:36:10,480 YEARS TRYING TO UNDERSTAND THE 3975 02:36:10,480 --> 02:36:13,040 NEUROLOGICAL UNDERPINNINGSES OF 3976 02:36:13,040 --> 02:36:14,960 THERAPY COGNITIVE IMPAIRMENT I 3977 02:36:14,960 --> 02:36:19,800 AND OTHERS DISCOVER BRAIN IMMON 3978 02:36:19,800 --> 02:36:22,040 IS REACTIVE TO IT. MICROGLIAL 3979 02:36:22,040 --> 02:36:23,080 CELLS HAVE IMPORTANT HOMEO 3980 02:36:23,080 --> 02:36:24,960 STATIC AND PLASTICITY FUNCTIONS 3981 02:36:24,960 --> 02:36:26,680 DISREGULATE ALL THOSE PROCESSES 3982 02:36:26,680 --> 02:36:29,680 I JUST TOLD YOU ABOUT AND 3983 02:36:29,680 --> 02:36:31,560 DISREGULATE HIPPOCAMPAL 3984 02:36:31,560 --> 02:36:32,920 NEUROGENESIS AND NEUROTOXICS 3985 02:36:32,920 --> 02:36:37,080 STATE OF ASTROCYTES AND IMPAIR 3986 02:36:37,080 --> 02:36:39,320 OLIGODENDROCYTE FUNCTION AND 3987 02:36:39,320 --> 02:36:41,240 INCLUDING HOMEOSTASIS AN 3988 02:36:41,240 --> 02:36:43,440 PLASTICITY. AFTER 3989 02:36:43,440 --> 02:36:44,680 CHEMOTHERAPEUTIC METHYL TREK 3990 02:36:44,680 --> 02:36:46,720 SATE PARTICULARLY ASSOCIATED 3991 02:36:46,720 --> 02:36:48,760 WITH SYNDROME OF COGNITIVE 3992 02:36:48,760 --> 02:36:51,360 IMPAIRMENT METHYL TREK SATE 3993 02:36:51,360 --> 02:36:53,120 INDUCES DIRECT ACTIVATION OF 3994 02:36:53,120 --> 02:36:54,480 MICROGLIA IN THE WHITE MATTER, 3995 02:36:54,480 --> 02:36:58,400 IN AXON TRACKS. THOSE REACTIVE 3996 02:36:58,400 --> 02:37:02,440 MICROGLIA THEN ACTIVATE 3997 02:37:02,440 --> 02:37:03,680 ASTROCYTES LUCY CREASE OF 3998 02:37:03,680 --> 02:37:04,640 SPECIFIC IMMUNE SIGNALING 3999 02:37:04,640 --> 02:37:06,800 MOLECULES AN TOGETHER REACTIVE 4000 02:37:06,800 --> 02:37:09,120 MICROGLIA AND ASTROCYTES 4001 02:37:09,120 --> 02:37:11,760 DISREGULATE THE OLIGODEN DR. 4002 02:37:11,760 --> 02:37:14,760 GLIAL LINEAGE DISRUPTING MYELIN 4003 02:37:14,760 --> 02:37:18,240 HOMEOSTASIS AND PLASTICITY, THIS 4004 02:37:18,240 --> 02:37:20,880 EXPERIENCE DEPENDENT TUNING SO 4005 02:37:20,880 --> 02:37:22,360 OF MYELIN SO IMPORTANT FOR 4006 02:37:22,360 --> 02:37:24,760 MEMORY AND LEARNING. MICROGLIAL 4007 02:37:24,760 --> 02:37:26,800 ARE ESSENTIAL TO THIS, WE CAN RE 4008 02:37:26,800 --> 02:37:29,960 RE RETHAT CAPITULATE IN BY 4009 02:37:29,960 --> 02:37:32,240 SYSTEMIC POLYSACCHARIDE AND 4010 02:37:32,240 --> 02:37:34,400 DEPLETE MICROGLIA USING 4011 02:37:34,400 --> 02:37:36,680 EXPERIMENTAL APPROACH USING CSF 4012 02:37:36,680 --> 02:37:39,000 1R INHIBITORS THAT DEPLETE 4013 02:37:39,000 --> 02:37:41,480 MYELOID CELLS BROADLY. THAT 4014 02:37:41,480 --> 02:37:43,480 RESCUES MYELINATION AND RESCUES 4015 02:37:43,480 --> 02:37:45,520 COGNITION AND PRE-CLINICAL 4016 02:37:45,520 --> 02:37:47,520 MODELS WE NODE THE MICROGLIA ARE 4017 02:37:47,520 --> 02:37:49,800 REALLY IMPORTANT. I WANT TO 4018 02:37:49,800 --> 02:37:51,120 SPEND A COUPLE OF MINUTES 4019 02:37:51,120 --> 02:37:52,960 TELLING YOU HOW CANCER THERAPIES 4020 02:37:52,960 --> 02:37:54,480 THAT ARE CHIEFLY IMMUNOLOGICAL 4021 02:37:54,480 --> 02:37:57,280 IN NATURE AND THEN ACTUALLY 4022 02:37:57,280 --> 02:37:59,200 MIMIC BROAD IMMUNE CHALLENGES 4023 02:37:59,200 --> 02:38:01,240 AND INDUCE THINGS LIKE CYTOKINE 4024 02:38:01,240 --> 02:38:04,920 RELEASE SYNDROME INDUCE THIS 4025 02:38:04,920 --> 02:38:05,920 PATHOPHYSIOLOGY IN THE BRAIN AS 4026 02:38:05,920 --> 02:38:07,200 WELL. I WAS WORRIED THAT 4027 02:38:07,200 --> 02:38:09,440 SYSTEMIC INFLAMMATION CAUSED BY 4028 02:38:09,440 --> 02:38:13,360 CANCER IMMUNOTHERAPIES LIKE CAR 4029 02:38:13,360 --> 02:38:15,560 T-CELL THERAPY CAUSE SIMILAR 4030 02:38:15,560 --> 02:38:17,120 NEUROINFLAMMATORY PHENOTYPE THAT 4031 02:38:17,120 --> 02:38:19,160 DISREGULATES GLIA AND THEREFORE 4032 02:38:19,160 --> 02:38:20,320 NEURAL CIRCUIT FUNCTION AND 4033 02:38:20,320 --> 02:38:23,680 COGNITION. AS A LOT OF PEOPLE IN 4034 02:38:23,680 --> 02:38:26,480 THIS CALL KNOW PROMISING FDA 4035 02:38:26,480 --> 02:38:28,440 APPROVED IMMUNOTHERAPY IS 4036 02:38:28,440 --> 02:38:30,280 CHIMERIC ANTIGEN RECEPTOR T-CELL 4037 02:38:30,280 --> 02:38:32,880 THERAPY, A PATIENT'S OWN T-CELLS 4038 02:38:32,880 --> 02:38:35,040 ARE TAKEN AND THEN ENGINEERED TO 4039 02:38:35,040 --> 02:38:37,640 TARGET SPECIFICALLY TARGET 4040 02:38:37,640 --> 02:38:39,040 ANTIGEN ON THEIR CANCER IN THE 4041 02:38:39,040 --> 02:38:41,320 CASE OF ACUTE LYMPHOBLASTIC 4042 02:38:41,320 --> 02:38:43,760 LEUKEMIA OR ALL THAT ANTIGEN 4043 02:38:43,760 --> 02:38:46,880 OFTEN CALLED CD 19 AND THEN 4044 02:38:46,880 --> 02:38:48,480 T-CELLS SEEK AND DESTROY THE 4045 02:38:48,480 --> 02:38:51,840 CANCER CELLS. THIS IS ASSOCIATED 4046 02:38:51,840 --> 02:38:54,320 WITH A VERY HIGH RATE OF 4047 02:38:54,320 --> 02:38:55,200 CYTOKINE RELEASE SYNDROME AS 4048 02:38:55,200 --> 02:38:57,640 WELL AS HIGH RATE OF I A CUTE 4049 02:38:57,640 --> 02:38:59,640 TRANSIENT NEUROLOGICAL SYMPTOMS 4050 02:38:59,640 --> 02:39:01,360 INCLUDING DELIRIUM AND 4051 02:39:01,360 --> 02:39:03,160 HALLUCINATIONS. THE LONG TERM 4052 02:39:03,160 --> 02:39:05,520 EFFECTS ON COGNITION ARE 4053 02:39:05,520 --> 02:39:06,560 UNDERSTUDIED BUT EARLY CLINICAL 4054 02:39:06,560 --> 02:39:08,640 REPORTS ARE FAIRLY CONCERNING 4055 02:39:08,640 --> 02:39:10,360 THAT A SIMILAR SYNDROME SIMILAR 4056 02:39:10,360 --> 02:39:12,160 TO CHEMOTHERAPY RELATED 4057 02:39:12,160 --> 02:39:13,040 COGNITIVE IMPAIRMENT IS 4058 02:39:13,040 --> 02:39:15,280 EMERGING. SO WE WONDERED WHETHER 4059 02:39:15,280 --> 02:39:18,720 CAR T-CELL THERAPY CAUSE SIMILAR 4060 02:39:18,720 --> 02:39:20,160 NEUROINFLAMMATORY CHANGES, 4061 02:39:20,160 --> 02:39:21,480 DISREGULATE NUMEROUS GLIAL 4062 02:39:21,480 --> 02:39:22,840 INTERACTIONS AND IMPAIR 4063 02:39:22,840 --> 02:39:24,320 COGNITION. THESE ARE PEOPLE IN 4064 02:39:24,320 --> 02:39:29,440 THE LAB WHO LED THIS PROJECT ANN 4065 02:39:29,440 --> 02:39:31,960 GARETY. WE LOOKED AT THREE 4066 02:39:31,960 --> 02:39:33,560 PRE-CLINICAL MODELS OF CAR 4067 02:39:33,560 --> 02:39:34,960 T-CELL THERAPY ONE THERAPY WE 4068 02:39:34,960 --> 02:39:37,400 ARE INTERESTED BECAUSE WE ARE 4069 02:39:37,400 --> 02:39:38,480 CURRENTLY LEADING CLINICAL WORK 4070 02:39:38,480 --> 02:39:41,520 IN THIS REALM TARGETING A 4071 02:39:41,520 --> 02:39:45,080 TERRIBLE MIDLINE GLIOMA CALLED 4072 02:39:45,080 --> 02:39:47,480 ACUTE TRANSITIVE GLIOMA AND CAR 4073 02:39:47,480 --> 02:39:48,440 T-CELL MODELS OUTSIDE THE 4074 02:39:48,440 --> 02:39:52,280 THERAPY SYSTEM, ONE FDA APPROVED 4075 02:39:52,280 --> 02:39:53,600 ANTI-CD 19 CAR T-CELL THERAPY 4076 02:39:53,600 --> 02:39:56,360 FOR LEUKEMIA AND THEN AS CANCER 4077 02:39:56,360 --> 02:39:58,880 THAT NEVER ENTERS THE NERVOUS 4078 02:39:58,880 --> 02:40:01,640 SYSTEM OSTEO SARCOMA. AND WE 4079 02:40:01,640 --> 02:40:04,360 LOOKED AT BOTH ON TARGET K FOR 4080 02:40:04,360 --> 02:40:05,880 CELLS THAT TARGET TUMOR AS WELL 4081 02:40:05,880 --> 02:40:08,600 AS OFF TARGET CAR T-CELLS THAT 4082 02:40:08,600 --> 02:40:10,280 TARGET ANTIGEN NOT EXPRESSED ON 4083 02:40:10,280 --> 02:40:12,280 TUMOR IN THAT MODEL TO CONTROL 4084 02:40:12,280 --> 02:40:14,760 FOR ON TARGET OFF TUMOR EFFECTS 4085 02:40:14,760 --> 02:40:17,160 AND FINALLY, A THIRD CONTROL 4086 02:40:17,160 --> 02:40:19,400 GROUP MOCK T-CELLS. WHAT WE FIND 4087 02:40:19,400 --> 02:40:21,760 IS THAT WE SEE COGNITIVE 4088 02:40:21,760 --> 02:40:22,720 DEFICITS AFTER CAR T-CELL 4089 02:40:22,720 --> 02:40:25,280 THERAPY IN MICE. WE SEE IN CNS 4090 02:40:25,280 --> 02:40:27,720 CAR T-CELL THERAPY AS WELL AS 4091 02:40:27,720 --> 02:40:29,920 T-CELL THERAPY FOR LEUKEMIA AND 4092 02:40:29,920 --> 02:40:32,000 OSTEO SARCOMA. ONLY SEEN WHEN 4093 02:40:32,000 --> 02:40:33,040 THERE IS EFFECTIVE IMMUNE 4094 02:40:33,040 --> 02:40:35,520 RESPONSE. IF WE LOOK AT OFF 4095 02:40:35,520 --> 02:40:37,600 TARGET CD 19 TARGETING CASH 4096 02:40:37,600 --> 02:40:39,760 T-CELL IN BRAIN CANCER MODEL 4097 02:40:39,760 --> 02:40:41,360 WHERE NO CD 19 ON CANCER WE 4098 02:40:41,360 --> 02:40:43,960 DON'T SEE COGNITIVE IMPAIRMENT 4099 02:40:43,960 --> 02:40:45,120 IN THAT PARTICULAR CASE. BUT IF 4100 02:40:45,120 --> 02:40:47,800 THE CAR T -- IF THE CD 19 4101 02:40:47,800 --> 02:40:49,960 TARGETING CAR T-CELLS NIGHT 4102 02:40:49,960 --> 02:40:51,440 LEUKEMIA AND THERE IS A TUMOR 4103 02:40:51,440 --> 02:40:53,560 CLEARING IMMUNE RESPONSE WE SEE 4104 02:40:53,560 --> 02:40:55,480 CD 19 CAR T-CELLS CAUSING 4105 02:40:55,480 --> 02:40:58,000 COGNITIVE IMPAIRMENT. TOGETHER 4106 02:40:58,000 --> 02:40:59,560 WITH THE COGNITIVE IMPAIRMENT 4107 02:40:59,560 --> 02:41:03,240 THERE IS PERSISTENT ELEVATION IN 4108 02:41:03,240 --> 02:41:04,960 CSF KITE INTOS AND CHEMOKINES 4109 02:41:04,960 --> 02:41:07,440 AFTER EACH -- KITEKINES AND 4110 02:41:07,440 --> 02:41:08,600 CHEMOKINES AFTER EACH T-CELL 4111 02:41:08,600 --> 02:41:13,160 STRATEGY AS WELL PASS SIMILAR -- 4112 02:41:13,160 --> 02:41:14,920 CYTOKINES AND CHEMOKINES. THIS 4113 02:41:14,920 --> 02:41:16,600 IS A POPULATION OF BRAIN 4114 02:41:16,600 --> 02:41:18,080 RESIDENT IMMUNE CELLS THAT ARE 4115 02:41:18,080 --> 02:41:21,600 VERY, VERY RESPONSIVE TO 4116 02:41:21,600 --> 02:41:23,440 SYSTEMIC IMMUNOTOXIC CHALLENGES. 4117 02:41:23,440 --> 02:41:25,760 WITH THE WHITE MATTER SPECIFIC 4118 02:41:25,760 --> 02:41:28,280 ELEVATION AND MICROGLIAL 4119 02:41:28,280 --> 02:41:30,120 ACTIVITY AFTER THERAPY WE SEE 4120 02:41:30,120 --> 02:41:32,720 DECREASE IN EACH MODEL AND 4121 02:41:32,720 --> 02:41:34,640 MYELINATING OLIGODENDROCYTES AND 4122 02:41:34,640 --> 02:41:37,680 DROP OUT OF MYELINATED AXONS. 4123 02:41:37,680 --> 02:41:39,360 TOGETHER WITH THAT, AS WE 4124 02:41:39,360 --> 02:41:41,920 PREDICT, BASED ON WHAT WE SEE 4125 02:41:41,920 --> 02:41:43,400 AFTER MORE TRADITIONAL CANCER 4126 02:41:43,400 --> 02:41:44,920 THERAPIES LIKE CHEMOTHERAPY AND 4127 02:41:44,920 --> 02:41:47,920 RADIATION WE SEE A DECREASE IN 4128 02:41:47,920 --> 02:41:48,680 HIPPOCAMPAL NEUROGENESIS THAT 4129 02:41:48,680 --> 02:41:52,080 CORRELATES WITH INCREASE IN HIP 4130 02:41:52,080 --> 02:41:53,920 CAM PAL WHITE MATTER MICROGLIAL 4131 02:41:53,920 --> 02:41:55,200 REACTIVITY. IF WE TARGET 4132 02:41:55,200 --> 02:41:56,680 MICROGLIA, DEPLETE 4133 02:41:56,680 --> 02:41:59,120 EXPERIMENTALLY USING CSFNR 4134 02:41:59,120 --> 02:42:02,280 INHIBITOR THAT RESCUES THE 4135 02:42:02,280 --> 02:42:03,240 OLIGODENDROCYTE PHENOTYPE 4136 02:42:03,240 --> 02:42:04,560 PARTIALLY AND RESCUES COGNITION 4137 02:42:04,560 --> 02:42:05,800 AT LEAST IN THIS TEST OF 4138 02:42:05,800 --> 02:42:07,640 ATTENTION AND MEMORY CALLED THE 4139 02:42:07,640 --> 02:42:11,880 NOVEL OBJECT RECOGNITION TEST. 4140 02:42:11,880 --> 02:42:12,960 SO WE THINK IMMUNOTHERAPY 4141 02:42:12,960 --> 02:42:16,440 RELATED COGNITIVE IMPAIRMENT 4142 02:42:16,440 --> 02:42:17,520 RECAPITULATES A SIMILAR 4143 02:42:17,520 --> 02:42:19,720 PRINCIPLE WE SEE AFTER CANCER 4144 02:42:19,720 --> 02:42:22,720 TRADITIONAL CHEMOTHERAPIES LIKE 4145 02:42:22,720 --> 02:42:24,440 METHYL TRACK SATE, A KNOWN -- 4146 02:42:24,440 --> 02:42:26,680 TREK SATE, ANONYM 4147 02:42:26,680 --> 02:42:28,920 IMMUNOCHALLENGE IN THE NERVOUS 4148 02:42:28,920 --> 02:42:31,120 SYSTEM WHICH TENDS TO BE 4149 02:42:31,120 --> 02:42:32,680 PERSISTENT AND LOCALIZED TO AXON 4150 02:42:32,680 --> 02:42:35,160 TRACKS THAT INDUCES NEURONAL AND 4151 02:42:35,160 --> 02:42:37,200 GLIAL DISREGULATION THAT THEN 4152 02:42:37,200 --> 02:42:39,160 RESULTS IN LASTING BRAIN FOG 4153 02:42:39,160 --> 02:42:43,080 SYNDROMES. WE KNOW THAT 4154 02:42:43,080 --> 02:42:44,880 ANTITUMOR CAR T-CELL THERAPIES 4155 02:42:44,880 --> 02:42:46,920 REQUIRED FOR THIS IS REALLY THE 4156 02:42:46,920 --> 02:42:48,160 IMMUNE RESPONSE WE BELIEVE IS 4157 02:42:48,160 --> 02:42:50,680 RESPONSIBLE FOR THE CNS 4158 02:42:50,680 --> 02:42:53,480 DISREGULATION. AND THE 4159 02:42:53,480 --> 02:42:55,360 DISREGULATING OLIGODENDROGLIAL 4160 02:42:55,360 --> 02:42:57,200 HOMEOSTASIS AND HIPPOCAMPAL 4161 02:42:57,200 --> 02:42:58,720 NEUROYENSIS IS IMPORTANT TO 4162 02:42:58,720 --> 02:42:59,840 PERSISTENT IMPAIRMENT IN 4163 02:42:59,840 --> 02:43:01,880 ATTENTION AND MEMORY. MICROGLIA 4164 02:43:01,880 --> 02:43:03,400 EMERGE AS AN INTERESTING 4165 02:43:03,400 --> 02:43:05,640 THERAPEUTIC TARGET, CSF 1R 4166 02:43:05,640 --> 02:43:06,840 INHIBITORS ARE NOT THE BEST WAY 4167 02:43:06,840 --> 02:43:08,720 TO DO IT CLINICALLY BUT IT 4168 02:43:08,720 --> 02:43:10,200 PRESENTS SOMETHING THAT WE CAN 4169 02:43:10,200 --> 02:43:14,720 WORK TOWARDS TARGETING. SO WHEN 4170 02:43:14,720 --> 02:43:17,920 THE PANDEMIC BEGAN IN -- WHEN I 4171 02:43:17,920 --> 02:43:19,920 BECAME AWARE OF IT IN 2020, I 4172 02:43:19,920 --> 02:43:22,160 WAS REALLY WORRIED SEEING HOW 4173 02:43:22,160 --> 02:43:25,240 VERY PROFOUNDLY IMMUNOGENIC CAR 4174 02:43:25,240 --> 02:43:27,680 COV-2 SEEMED TO BE. I WORRIED WE 4175 02:43:27,680 --> 02:43:29,560 WOULD BEGIN TO SEE COGNITIVE 4176 02:43:29,560 --> 02:43:31,760 IMPAIRMENT AS AFTER CHEMOTHERAPY 4177 02:43:31,760 --> 02:43:33,720 AND AFTER CAR T-CELL THERAPY. 4178 02:43:33,720 --> 02:43:36,000 AND VERY QUICKLY BECAME EVIDENT 4179 02:43:36,000 --> 02:43:38,600 EVEN PEOPLE WHO HAD EXPERIENCE 4180 02:43:38,600 --> 02:43:40,720 RELATIVELY MILD RESPIRATORY 4181 02:43:40,720 --> 02:43:42,200 COVID, WERE COMING TO THE 4182 02:43:42,200 --> 02:43:44,200 NEUROLOGIST OFFICE IN DROVES 4183 02:43:44,200 --> 02:43:45,640 WITH VERY SIMILAR SYNDROME OF 4184 02:43:45,640 --> 02:43:46,840 IMPAIRED ATTENTION, 4185 02:43:46,840 --> 02:43:48,960 CONCENTRATION, MEMORY, SPEED OF 4186 02:43:48,960 --> 02:43:50,000 INFORMATION, PROCESSING 4187 02:43:50,000 --> 02:43:51,320 MULTI-TASKING AND COGNITIVE 4188 02:43:51,320 --> 02:43:53,720 FATIGUE. AND JUST LIKE AFTER 4189 02:43:53,720 --> 02:43:55,600 CANCER THERAPIES, STANDARDS 4190 02:43:55,600 --> 02:43:57,560 NEURAL IMAGING IS TYPICALLY 4191 02:43:57,560 --> 02:43:59,280 UNREMARKABLE BUT ADVANCE 4192 02:43:59,280 --> 02:44:00,960 NEUROIMAGING REVEALS CELL WHITE 4193 02:44:00,960 --> 02:44:02,960 MATTER ABERRATIONS AND DECREASED 4194 02:44:02,960 --> 02:44:04,960 VOLUME IN THIS CASE LIMB BIC AS 4195 02:44:04,960 --> 02:44:06,400 WELL AS OLFACTORY STRUCTURES. 4196 02:44:06,400 --> 02:44:08,000 THIS AFFECTS A LARGE PORTION OF 4197 02:44:08,000 --> 02:44:10,440 COVID SURVIVORS THE NUMBERS VARY 4198 02:44:10,440 --> 02:44:11,600 DEPENDING ON THE MEASURE THAT 4199 02:44:11,600 --> 02:44:13,800 ONE IS USING BUT ONE META 4200 02:44:13,800 --> 02:44:16,040 ANALYSIS OF 10,000 SUBJECTS 4201 02:44:16,040 --> 02:44:17,960 FOUND THAT AS MANY AS ONE IN 4202 02:44:17,960 --> 02:44:19,480 FOUR PEOPLE EXPERIENCE SOME 4203 02:44:19,480 --> 02:44:21,880 DEGREE OF PERSISTENT COGNITIVE 4204 02:44:21,880 --> 02:44:24,320 DYSFUNCTION. SO WE WONDERED 4205 02:44:24,320 --> 02:44:25,280 WHETHER SIMILAR GLIAL 4206 02:44:25,280 --> 02:44:27,520 DISREGULATION MAY CONTRIBUTE TO 4207 02:44:27,520 --> 02:44:28,280 COGNITIVE SYMPTOMS AFTER COVID. 4208 02:44:28,280 --> 02:44:31,600 AND TO ANSWER THOSE QUESTIONS, I 4209 02:44:31,600 --> 02:44:33,400 REACHED OUT TO IN THE MIDST OF 4210 02:44:33,400 --> 02:44:34,520 LOCK DOWN COLLABORATED WITH 4211 02:44:34,520 --> 02:44:36,800 THESE TWO WONDERFUL PEOPLE, 4212 02:44:36,800 --> 02:44:40,040 AKIKO AT YALE AND AVINDA AT 4213 02:44:40,040 --> 02:44:40,920 NINDS TOGETHER WITH MANY PEOPLE 4214 02:44:40,920 --> 02:44:45,640 FROM OUR LABS. WE USED A MODEL 4215 02:44:45,640 --> 02:44:48,480 SYSTEM DEVELOPED IN AKIKO'S LAB 4216 02:44:48,480 --> 02:44:50,800 OF MILD RESPIRATORY RESTRICTED 4217 02:44:50,800 --> 02:44:52,760 SARS COV-2, SO IN THIS MOUSE 4218 02:44:52,760 --> 02:44:53,880 MODEL WE CAN RESTRICT INFECTION 4219 02:44:53,880 --> 02:44:55,440 TO RESPIRATORY TRACT. IN THIS 4220 02:44:55,440 --> 02:44:56,920 MODEL A MILD DISEASE MICE CLEAR 4221 02:44:56,920 --> 02:44:58,800 THE VIRUS WITHIN ABOUT SEVIN 4222 02:44:58,800 --> 02:45:00,920 DAYS IN THE RESPIRATORY SYSTEM, 4223 02:45:00,920 --> 02:45:02,320 THEY DON'T LOSE WEIGHT, THEY 4224 02:45:02,320 --> 02:45:04,400 CONTINUE TO GROOM WELL, THERE'S 4225 02:45:04,400 --> 02:45:05,200 NO EVIDENCE OF INFECTION IN THE 4226 02:45:05,200 --> 02:45:10,120 BRAIN. AND YET WHEN WE LOOK 4227 02:45:10,120 --> 02:45:12,200 EITHER 7 DAYS OR WEEKS T A SERA 4228 02:45:12,200 --> 02:45:15,960 OR CSF WE CAESARSIS TENT 4229 02:45:15,960 --> 02:45:17,520 PROFOUND ELEVATION IN BOTH SERUM 4230 02:45:17,520 --> 02:45:20,760 AND CSF KITE SIGNS AND 4231 02:45:20,760 --> 02:45:22,520 CHEMOKINES. -- CYTOKINES AND 4232 02:45:22,520 --> 02:45:25,680 CHEMOKINES. THIS RESPIRATORY 4233 02:45:25,680 --> 02:45:27,600 CHALLENGE IS BEING SUBMITTED 4234 02:45:27,600 --> 02:45:29,680 BECOMING NEUROINFLAMMATION. AS 4235 02:45:29,680 --> 02:45:33,920 WE SAW WITH CHEMOTHERAPY AND CAR 4236 02:45:33,920 --> 02:45:35,520 T-CELL CHEMOTHERAPY THERE IS A 4237 02:45:35,520 --> 02:45:38,760 REACTIVITY OF MICROGLIA AND 4238 02:45:38,760 --> 02:45:40,560 GENETIC STRAINS OF MICE AND 4239 02:45:40,560 --> 02:45:42,000 HUMANS WHO DIED EARLY IN THE 4240 02:45:42,000 --> 02:45:43,600 PANDEMIC WITH SARS COV-2 4241 02:45:43,600 --> 02:45:45,760 INFECTION BUT WHO DID NOT HAVE 4242 02:45:45,760 --> 02:45:47,400 SEVERE LUNG DISEASE. THERE WAS 4243 02:45:47,400 --> 02:45:48,880 NO EVIDENCE OF INFECTION IN THE 4244 02:45:48,880 --> 02:45:51,440 BRAINS OF THESE PEOPLE AND YET 4245 02:45:51,440 --> 02:45:53,200 THERE WAS WHITE MATTER SELECTIVE 4246 02:45:53,200 --> 02:45:54,040 ELEVATION IN MICROGLIAL 4247 02:45:54,040 --> 02:45:58,920 REACTIVITY. AS WE PREDICT, WE 4248 02:45:58,920 --> 02:46:01,160 SEE AGAIN THIS LOSS OF 4249 02:46:01,160 --> 02:46:03,120 OLIGODENDROCYTES, THIS HAPPENS 4250 02:46:03,120 --> 02:46:05,240 QUICKLY AFTER MILD RESPIRATORY 4251 02:46:05,240 --> 02:46:08,720 SARS COV-2 IN MICE BY 7 DAYS 4252 02:46:08,720 --> 02:46:11,280 THROUGH 7 WEEKS. WE SEE A DROP 4253 02:46:11,280 --> 02:46:14,480 OUT IN MYELINATED AXONS IN THE 4254 02:46:14,480 --> 02:46:16,200 SUB CORTICAL WHITE MATTER 4255 02:46:16,200 --> 02:46:18,400 EVIDENT AT 7 DAYS AND 7 WEEKS 4256 02:46:18,400 --> 02:46:20,920 AND THIS IS MEASURE OF THE KIND 4257 02:46:20,920 --> 02:46:23,520 OF LOSS OF MYELINATED AXONS WE 4258 02:46:23,520 --> 02:46:26,160 SEE AFTER METHYL TREXATE 4259 02:46:26,160 --> 02:46:27,320 CHEMOTHER THIS PI COMPARING THE 4260 02:46:27,320 --> 02:46:30,520 DECREASE IN EACH CASE. -- 4261 02:46:30,520 --> 02:46:32,280 THERAPY. WHAT WE KNOW FROM 4262 02:46:32,280 --> 02:46:34,800 CANCER THERAPY RELATED 4263 02:46:34,800 --> 02:46:35,840 NEUROBIOLOGY WE FIND THAT THERE 4264 02:46:35,840 --> 02:46:38,200 IS A DECREASE IN HIPPOCAMPAL 4265 02:46:38,200 --> 02:46:42,080 NEUROGENESIS THAT IS PERSISTENT 4266 02:46:42,080 --> 02:46:44,600 AND WE NOTICED RELEVANT TO THAT, 4267 02:46:44,600 --> 02:46:46,120 THAT THERE WAS PERSISTENT 4268 02:46:46,120 --> 02:46:48,360 ELEVATION OF CHEMOKINE CALLED 4269 02:46:48,360 --> 02:46:51,600 CCL 11 AND CSF OF MICE FOLLOWING 4270 02:46:51,600 --> 02:46:53,720 MILD RESPIRATORY SARS COV-2. 4271 02:46:53,720 --> 02:46:55,400 THAT WAS REALLY INTERESTED 4272 02:46:55,400 --> 02:46:58,120 BECAUSE CCL 11 IS ASSOCIATED 4273 02:46:58,120 --> 02:47:02,440 WITH DECREASED HIPPOCAMPAL 4274 02:47:02,440 --> 02:47:03,920 MYELINATION WITH AGING. SO WE 4275 02:47:03,920 --> 02:47:06,160 COLLABORATED WITH DAVID A REHAB 4276 02:47:06,160 --> 02:47:07,640 MEDICINE SPECIALIST WHO 4277 02:47:07,640 --> 02:47:09,080 SPECIALIZES NOW IN LONG COVID 4278 02:47:09,080 --> 02:47:10,960 AND IN HIS COHORT OF PATIENTS WE 4279 02:47:10,960 --> 02:47:14,200 FOUND THAT THOSE WITH LONG COVID 4280 02:47:14,200 --> 02:47:17,560 WHO HAD COMPLAINED WITH 4281 02:47:17,560 --> 02:47:20,320 SELF-REPORTS REPORTED COGNITIVE 4282 02:47:20,320 --> 02:47:22,160 SYMPTOMS COMPARED TO THOSE WITH 4283 02:47:22,160 --> 02:47:22,840 WITH NOT THERE WAS INCREASE IN 4284 02:47:22,840 --> 02:47:25,200 SERUM CCL 11 LEVELS. THERE IS A 4285 02:47:25,200 --> 02:47:26,000 LARGE SPREAD HERE IN THE DATA 4286 02:47:26,000 --> 02:47:28,280 AND SO WE DID A MULTI-VARIANT 4287 02:47:28,280 --> 02:47:29,960 ANALYSIS AND FOUND THAT IN THOSE 4288 02:47:29,960 --> 02:47:33,640 THAT HAD A HISTORY OF BRAIN FOG 4289 02:47:33,640 --> 02:47:34,720 SELF-REPORTED BRAIN FOG WITH 4290 02:47:34,720 --> 02:47:36,920 ELEVATED CCL 11 LEVELS, THAT 4291 02:47:36,920 --> 02:47:39,280 THAT CORRELATED WITH A HISTORY 4292 02:47:39,280 --> 02:47:41,120 OF AUTOIMMUNE DISEASE SUGGESTING 4293 02:47:41,120 --> 02:47:43,600 SOMETHING ABOUT THE PATIENT'S 4294 02:47:43,600 --> 02:47:45,040 IMMUNE SYSTEM MAY DISREGULATE 4295 02:47:45,040 --> 02:47:46,880 THIS RESPONSE AND INCREASE THE 4296 02:47:46,880 --> 02:47:49,880 RISK OF ELEVATED CCL 11 WHICH 4297 02:47:49,880 --> 02:47:50,880 CORRELATES WITH COGNITIVE 4298 02:47:50,880 --> 02:47:52,480 IMPAIRMENT. SO WE WONDERED 4299 02:47:52,480 --> 02:47:54,680 WHETHER CCL 11 WAS CAUSATIVE OR 4300 02:47:54,680 --> 02:47:57,400 CORRELATIVE. SO WE TOOK HEALTHY 4301 02:47:57,400 --> 02:47:59,920 MICE AND JUST ADMINISTERED CCL 4302 02:47:59,920 --> 02:48:02,200 11 SYSTEMICALLY. WHAT WE FOUND 4303 02:48:02,200 --> 02:48:04,760 IS THAT THAT ADMINISTRATION 4304 02:48:04,760 --> 02:48:06,920 PARADIGM RESULTED IN NO INCREASE 4305 02:48:06,920 --> 02:48:08,080 IN MICROGLIAL REACTIVITY IN THE 4306 02:48:08,080 --> 02:48:10,120 CORTEX OR SUB CORTICAL WHITE 4307 02:48:10,120 --> 02:48:12,880 MATTER BUT WE DID SEE THAT THAT 4308 02:48:12,880 --> 02:48:15,680 SYSTEMIC CCL 11 INCREASED 4309 02:48:15,680 --> 02:48:16,920 HIPPOCAMPAL WHITE MATTER 4310 02:48:16,920 --> 02:48:17,920 MICROGLIAL REACTIVITY AND THAT 4311 02:48:17,920 --> 02:48:20,560 WAS SUFFICIENT TO DECREASE 4312 02:48:20,560 --> 02:48:23,760 HIPPOCAMPAL NEUROGENESIS. CCL 1 4313 02:48:23,760 --> 02:48:25,360 # 1 IS ONE MECHANISTIC COMPONENT 4314 02:48:25,360 --> 02:48:27,080 BUT NOT THE ONLY WAY LUNG IMMUNE 4315 02:48:27,080 --> 02:48:29,760 CHALLENGE IS TRANSMITTED TO CNS 4316 02:48:29,760 --> 02:48:32,320 IMMUNE CHALLENGE. I HAVE TWO 4317 02:48:32,320 --> 02:48:34,400 SLIDES LEFT. GOING TO FINISH ONE 4318 02:48:34,400 --> 02:48:36,240 MINUTE LATE. I APOLOGIZE. SO WE 4319 02:48:36,240 --> 02:48:37,040 WONDERED WHETHER THIS WAS 4320 02:48:37,040 --> 02:48:38,320 SPECIFIC TO COVID OR WHETHER 4321 02:48:38,320 --> 02:48:40,880 THIS WAS A MORE BROAD REFLECTION 4322 02:48:40,880 --> 02:48:43,160 OF RESPIRATORY IMMUNE CHALLENGE. 4323 02:48:43,160 --> 02:48:45,720 SO WE TREATED MICE, THE INFECTED 4324 02:48:45,720 --> 02:48:48,440 MICE WITH A MOUSE MODEL MILD 4325 02:48:48,440 --> 02:48:50,560 RESPIRATORY INFLUENZA. AND THEN 4326 02:48:50,560 --> 02:48:53,520 WE EXAMINED THE BRAIN 7 DAYS OR 4327 02:48:53,520 --> 02:48:54,920 7 WEEKS LATER AND FOUND THAT 4328 02:48:54,920 --> 02:48:56,960 AFTER MILD RESPIRATORY INFLUENZA 4329 02:48:56,960 --> 02:48:59,240 THERE WAS A TRANSIENT SUB 4330 02:48:59,240 --> 02:49:01,160 CORTICAL WHITE MATTER MICROGLIAL 4331 02:49:01,160 --> 02:49:02,840 REACTIVITY AFTER COVID AT 7 DAYS 4332 02:49:02,840 --> 02:49:04,880 WE SAW MICROGLIAL REACTIVITY 4333 02:49:04,880 --> 02:49:06,760 BOTH IN THE HIPPOCAMPAL WHITE 4334 02:49:06,760 --> 02:49:09,880 MATTER AND SUB CORTICAL WHITE 4335 02:49:09,880 --> 02:49:13,240 MATTER. AFTER 7 WEEKS THOUGH, 4336 02:49:13,240 --> 02:49:16,720 THAT SUB CORTICAL WHITE MATTER 4337 02:49:16,720 --> 02:49:21,440 MICROGLIAL REACTIVITY RESOLVED 4338 02:49:21,440 --> 02:49:22,120 INFLUENZA WHILE THE OTHER 4339 02:49:22,120 --> 02:49:24,320 PERSISTED. WE SAW A RESOLUTION 4340 02:49:24,320 --> 02:49:27,920 OF POST INFLUENZA 4341 02:49:27,920 --> 02:49:30,560 OLIGODENDROCYTE LOSS BY 7 WEEKS 4342 02:49:30,560 --> 02:49:34,360 AND SYSTEMIC OF HIPPOCAMPAL. IN 4343 02:49:34,360 --> 02:49:36,800 THE CYTOKINE AND CHEMOKINE AFTER 4344 02:49:36,800 --> 02:49:38,680 COVID AND INFLEW INFLUENZA THERE 4345 02:49:38,680 --> 02:49:41,320 IS PERSISTENT ELEVATION OF CCL 4346 02:49:41,320 --> 02:49:43,680 11 WHICH SPECIFICALLY AFFECTED 4347 02:49:43,680 --> 02:49:44,840 HIPPOCAMPUS. THERE IS ALSO 4348 02:49:44,840 --> 02:49:47,640 REALLY INTERESTED DIFFERENCES 4349 02:49:47,640 --> 02:49:49,720 THOUGH. AFTER COVID THERE IS 4350 02:49:49,720 --> 02:49:53,880 ACUTE ELEVATION IN THE CSF 4351 02:49:53,880 --> 02:49:55,480 INTERLEUKIN 7 AND INTERLEUKIN 4352 02:49:55,480 --> 02:49:57,080 ALPHA THAT RESOLVES AFTER 4353 02:49:57,080 --> 02:49:59,960 INFLUENZA, YOU DON'T SEE IL 6 4354 02:49:59,960 --> 02:50:01,720 ELEVATION UNTIL LATER IN DISEASE 4355 02:50:01,720 --> 02:50:03,320 COURSE, CURRENTLY TRYING TO 4356 02:50:03,320 --> 02:50:05,920 UNDERSTAND HOW THE DIFFERENCES 4357 02:50:05,920 --> 02:50:08,720 IN SIGHT COIN AND CHEMOKINE 4358 02:50:08,720 --> 02:50:09,840 PROFILES IMMUNE CHALLENGES BY 4359 02:50:09,840 --> 02:50:12,320 THE SAME ORGAN MIGHT BE 4360 02:50:12,320 --> 02:50:13,640 DIDN'TIALLY AFFECTING DIFFERENT 4361 02:50:13,640 --> 02:50:15,040 NEURAL CIRCUITS LONG TERM. SO I 4362 02:50:15,040 --> 02:50:16,400 WOULD LIKE TO CONCLUDE WITH THE 4363 02:50:16,400 --> 02:50:18,560 IDEA THAT SYSTEMIC IMMUNE 4364 02:50:18,560 --> 02:50:21,120 CHALLENGES CAUSE 4365 02:50:21,120 --> 02:50:22,640 NEUROINFLAMMATORY CHANGES AND 4366 02:50:22,640 --> 02:50:26,480 CONSEQUENT GLIAL DISREGULATION 4367 02:50:26,480 --> 02:50:27,880 THAT INDUCES NEURAL CIRCUMSTANCE 4368 02:50:27,880 --> 02:50:28,880 DYSFUNCTION AND CAUSES COGNITIVE 4369 02:50:28,880 --> 02:50:30,440 IMPAIRMENT. THIS SEEMS TO BE A 4370 02:50:30,440 --> 02:50:34,320 SORT OF COHESIVE PRINCIPLE OF 4371 02:50:34,320 --> 02:50:36,720 WAYS WHICH PREFERRIAL IMMUNE 4372 02:50:36,720 --> 02:50:37,520 CHALLENGES INFLUENCE THE BRAIN 4373 02:50:37,520 --> 02:50:42,480 IN LONG TERM WAY. THINKING COVID 4374 02:50:42,480 --> 02:50:44,240 IN PARTICULAR THIS RESPIRATORY 4375 02:50:44,240 --> 02:50:47,920 IMMUNE CHALLENGE INDUCE 4376 02:50:47,920 --> 02:50:49,600 NEUROINFLAMMATION AND GLIAL 4377 02:50:49,600 --> 02:50:53,120 DISREGULATION IS LIKELY COMMON 4378 02:50:53,120 --> 02:50:56,120 MECHANISM OF BRAIN FOG AND 4379 02:50:56,120 --> 02:50:57,120 NEUROBIOLOGICAL DYSFUNCTION BUT 4380 02:50:57,120 --> 02:50:59,000 THERE IS CERTAINLY MANY OTHER 4381 02:50:59,000 --> 02:50:59,880 THINGS THAT CAN HAPPEN 4382 02:50:59,880 --> 02:51:02,760 ESPECIALLY CRITICAL ILLNESS LIKE 4383 02:51:02,760 --> 02:51:05,240 COVID AND MANY OTHERS. WE HAVE 4384 02:51:05,240 --> 02:51:08,320 TO ALSO CONSIDER THINGS THAT 4385 02:51:08,320 --> 02:51:09,720 HAPPEN ALSO IN VARIOUS 4386 02:51:09,720 --> 02:51:13,560 COMBINATIONS INCLUDING 4387 02:51:13,560 --> 02:51:14,960 AUTO-IMMUNITY, NEUROINVASIVE 4388 02:51:14,960 --> 02:51:16,320 INFECTION, REACTIVATION OF OTHER 4389 02:51:16,320 --> 02:51:19,000 INFECTIONS IN THE CASE OF COVID, 4390 02:51:19,000 --> 02:51:22,880 REACTIVATION OF EBB SEEMS COMMON 4391 02:51:22,880 --> 02:51:25,120 THROMBOTIC AND MICROVASCULAR 4392 02:51:25,120 --> 02:51:27,240 DISEASE AND MENTAL ILLNESS 4393 02:51:27,240 --> 02:51:28,600 MULTI-ORGAN FAILURE CONTRIBUTES 4394 02:51:28,600 --> 02:51:29,920 TO NUMEROUS METABOLIC 4395 02:51:29,920 --> 02:51:31,400 DISTURBANCES THAT INFLUENCE THE 4396 02:51:31,400 --> 02:51:32,800 BRAIN IN PERMANENT DETRIMENTAL 4397 02:51:32,800 --> 02:51:38,480 WAYS. OUR GAPS IN KNOWLEDGE 4398 02:51:38,480 --> 02:51:39,720 INCLUDE UNDERSTANDING IN 4399 02:51:39,720 --> 02:51:40,640 COMPREHENSIVE WAY HOW 4400 02:51:40,640 --> 02:51:42,120 INFLAMMATORY SIGNALS ARE 4401 02:51:42,120 --> 02:51:44,320 TRANSMITTED FROM LUNG TO BRAIN. 4402 02:51:44,320 --> 02:51:46,000 I WOULD LIKE TO UNDERSTAND WHY 4403 02:51:46,000 --> 02:51:48,000 WHITE MATTER MICROGLIA SEEM SO 4404 02:51:48,000 --> 02:51:49,720 SENSITIVE TO IMMUNE CHALLENGES 4405 02:51:49,720 --> 02:51:52,160 AND REMAIN ACTIVE IN SUCH 4406 02:51:52,160 --> 02:51:53,400 PERSISTENT WAY. AFTER MANY 4407 02:51:53,400 --> 02:51:56,400 CHALLENGES. THE ROLE THAT 4408 02:51:56,400 --> 02:51:58,320 NEUROTOXIC ASTROCYTES PLAY IN 4409 02:51:58,320 --> 02:52:00,760 COGNITIVE IMPAIRMENT IN NON-CNS 4410 02:52:00,760 --> 02:52:03,400 IMMUNE CHALLENGE REMAINS FULLY 4411 02:52:03,400 --> 02:52:05,240 UNDERSTOOD AND QUITE IMPORTANT. 4412 02:52:05,240 --> 02:52:07,560 AND OF COURSE HOW CAN WE TAKE 4413 02:52:07,560 --> 02:52:09,080 THESE NEW UNDERSTANDINGS AND 4414 02:52:09,080 --> 02:52:12,600 LEVERAGE FOR THERAPY. HOW WE USE 4415 02:52:12,600 --> 02:52:14,000 TO DEVELOP NEW TREATMENTS, HOW 4416 02:52:14,000 --> 02:52:16,680 CAN WE RESTORE HEALTHY 4417 02:52:16,680 --> 02:52:17,400 NEUROCIRCUIT HOMEOSTASIS AND 4418 02:52:17,400 --> 02:52:18,800 PLASTICITY TO RESCUE COGNITION. 4419 02:52:18,800 --> 02:52:20,480 SO I WILL CONCLUDE AT THE HIGH 4420 02:52:20,480 --> 02:52:23,640 RISK HIGH REWARD IDEA THAT A 4421 02:52:23,640 --> 02:52:25,960 COMMON PRINCIPLE OF BRAIN FOG 4422 02:52:25,960 --> 02:52:28,400 SYNDROMES ARE EMERGING. AND 4423 02:52:28,400 --> 02:52:30,840 MICROGLIAL REACTIVITY IS 4424 02:52:30,840 --> 02:52:32,480 ESSENTIAL. SO CAN WE DISCOVER 4425 02:52:32,480 --> 02:52:34,400 WAYS TO COACH MICROGLIA FROM 4426 02:52:34,400 --> 02:52:37,320 REACTIVE STATE TO A MORE 4427 02:52:37,320 --> 02:52:38,440 HOMEOSTATIC STATE. AND 4428 02:52:38,440 --> 02:52:39,480 UNDERSTANDING THAT IS GOING TO 4429 02:52:39,480 --> 02:52:41,880 BE RELEVANT TO A NUMBER OF 4430 02:52:41,880 --> 02:52:43,800 DIFFERENT NEUROLOGICAL 4431 02:52:43,800 --> 02:52:45,920 DISORDERS. MANY PEOPLE TO THANK 4432 02:52:45,920 --> 02:52:46,960 SORRY FOR GOING OVER MY TIME. 4433 02:52:46,960 --> 02:52:47,880 THANK YOU VERY MUCH FOR YOUR 4434 02:52:47,880 --> 02:52:48,920 ATTENTION. LOOK FORWARD TO 4435 02:52:48,920 --> 02:52:51,320 DISCUSSION. 4436 02:52:51,320 --> 02:52:51,960 >> MICHELLE, THANK YOU FOR 4437 02:52:51,960 --> 02:52:54,320 SETTING US UP ON A GOOD 4438 02:52:54,320 --> 02:52:56,560 TRAJECTORY TO START, PHENOMENAL 4439 02:52:56,560 --> 02:52:57,400 WORK. COUPLE O QUESTIONS FROM 4440 02:52:57,400 --> 02:52:59,360 THE AUDIENCE BASED UPON YOUR 4441 02:52:59,360 --> 02:53:02,160 TALK. THE FIRST COMES FROM 4442 02:53:02,160 --> 02:53:03,760 TAREK, A SPEAKER IN ABOUT 45 4443 02:53:03,760 --> 02:53:05,760 MINUTES. HE'S WONDERING HE 4444 02:53:05,760 --> 02:53:08,760 MENTIONS THAT MICROGLIA CAN HAVE 4445 02:53:08,760 --> 02:53:10,480 NEUROTOXIC AND NEUROPROTECTIVE 4446 02:53:10,480 --> 02:53:12,200 PROFILES. DO YOU HAVE A SENSE OF 4447 02:53:12,200 --> 02:53:15,640 WAYS TO MONITOR FOR USING 4448 02:53:15,640 --> 02:53:16,640 BIOMARKERS PERIPHERALLY OR 4449 02:53:16,640 --> 02:53:19,520 OTHERS TO ASSESS WHETHER 4450 02:53:19,520 --> 02:53:21,320 MICROGLIA ARE DOING GOOD OR BAD? 4451 02:53:21,320 --> 02:53:22,320 >> IT IS SUCH AN IMPORTANT 4452 02:53:22,320 --> 02:53:26,560 QUESTION. SO MICROGLIA ASSUME 4453 02:53:26,560 --> 02:53:29,120 MANY REACTIVE STATES, SOME 4454 02:53:29,120 --> 02:53:32,760 HELPFUL SOME HARMFUL, THEY DO 4455 02:53:32,760 --> 02:53:33,960 IMPORTANT PROCESSES SO CAN'T GET 4456 02:53:33,960 --> 02:53:35,760 RID OF THEM. QUESTION IS WHAT 4457 02:53:35,760 --> 02:53:37,920 DISEASE ASSOCIATED STATE ARE IN, 4458 02:53:37,920 --> 02:53:39,440 THERE ARE NUMEROUS DISEASE 4459 02:53:39,440 --> 02:53:41,920 ASSOCIATED STATES IN MICROGLIAL 4460 02:53:41,920 --> 02:53:43,360 DESCRIBED. WE HAVE DONE SINGLE 4461 02:53:43,360 --> 02:53:47,560 CELL SEQUENCING OF MICROGLIA 4462 02:53:47,560 --> 02:53:49,000 AFTER SARS COV-2 INNEXT IN MICE 4463 02:53:49,000 --> 02:53:51,720 AND THE STATE MICROGLIA ARE IN 4464 02:53:51,720 --> 02:53:53,320 SHARES A LOT OF FEATURES WITH 4465 02:53:53,320 --> 02:53:55,160 VARIOUS OTHER DISEASE ASSOCIATED 4466 02:53:55,160 --> 02:53:57,840 MICROGLIA, WE THINK IT IS NOT 4467 02:53:57,840 --> 02:53:59,960 HELPFUL, IT IS NEUROTOXIC BUT 4468 02:53:59,960 --> 02:54:02,640 THERE IS UNIQUE FEATURES OF 4469 02:54:02,640 --> 02:54:06,080 MICROGLIA AFTER SARS COV-2 4470 02:54:06,080 --> 02:54:07,680 INFECTION CHEMOKINE EXPRESSION. 4471 02:54:07,680 --> 02:54:09,560 AS WE UNDERSTAND MORE AND 4472 02:54:09,560 --> 02:54:10,960 IDENTIFY EXACTLY WHICH 4473 02:54:10,960 --> 02:54:12,120 CHEMOKINES ARE CONSISTENTLY 4474 02:54:12,120 --> 02:54:14,720 EXPRESSED BY MICROGLIA IN THIS 4475 02:54:14,720 --> 02:54:16,280 NEUROTOXIC STATE WE MAY THEN BE 4476 02:54:16,280 --> 02:54:21,080 ABLE TO DEVELOP A CSF OR 4477 02:54:21,080 --> 02:54:26,480 POTENTIALLY PROBABLY CSF BIOMOCK 4478 02:54:26,480 --> 02:54:28,200 ER TO MONITOR STATE BUT 4479 02:54:28,200 --> 02:54:31,560 THE FIELD TRYING TO MONITOR 4480 02:54:31,560 --> 02:54:32,080 ENTIRE STATES. 4481 02:54:32,080 --> 02:54:33,760 >> MICHELLE WILL HAVE MORE 4482 02:54:33,760 --> 02:54:36,880 QUESTIONS DURING POST SESSION. 4483 02:54:36,880 --> 02:54:40,080 THANK YOU MORE THE TIME. NEXT 4484 02:54:40,080 --> 02:54:42,440 SPEAKER TROY STEVENS, Ph.D. 4485 02:54:42,440 --> 02:54:43,320 FROM UNIVERSITY OF SOUTH 4486 02:54:43,320 --> 02:54:46,200 ALABAMA. HE IS THE WILL NOR LOCK 4487 02:54:46,200 --> 02:54:47,880 PROFESSOR AND CHAIR DEPARTMENT 4488 02:54:47,880 --> 02:54:49,320 OF PHYSIOLOGY AND CELL BIOLOGY 4489 02:54:49,320 --> 02:54:51,320 AT SOUTH ALABAMA, DOES REALLY 4490 02:54:51,320 --> 02:54:52,720 INCREDIBLE WORK AS DIRECTOR FOR 4491 02:54:52,720 --> 02:54:53,880 THE CENTER FOR LUNG BIOLOGY. 4492 02:54:53,880 --> 02:54:55,800 HE'S GOING TO BE TALKING ABOUT 4493 02:54:55,800 --> 02:54:57,080 INTERACTION BETWEEN LUNG AND 4494 02:54:57,080 --> 02:54:59,040 BRAIN WHICH IS BROUGHT UP IN THE 4495 02:54:59,040 --> 02:55:01,520 CHAT ALREADY SPECIFICALLY 4496 02:55:01,520 --> 02:55:02,920 INTERESTED IN HOST PATHOGEN 4497 02:55:02,920 --> 02:55:04,440 INTERACTION AND HOW THAT MIGHT 4498 02:55:04,440 --> 02:55:05,680 AFFECT THE BRAIN. SO EXCITED 4499 02:55:05,680 --> 02:55:07,560 TROY TO HAVE YOU TODAY. LET YOU 4500 02:55:07,560 --> 02:55:07,960 GET GOING. 4501 02:55:07,960 --> 02:55:09,800 >> GREAT. THANK YOU SO MUCH FOR 4502 02:55:09,800 --> 02:55:10,680 THE OPPORTUNITY TO BE HERE. 4503 02:55:10,680 --> 02:55:13,880 REALLY EXCITED TO TALK ABOUT 4504 02:55:13,880 --> 02:55:16,240 WORK OUR LARGER GROUP HAS BEEN 4505 02:55:16,240 --> 02:55:18,360 PERFORMING TO TRY TO ADDRESS 4506 02:55:18,360 --> 02:55:20,280 THIS IMPORTANT PROBLEM. TITLE IS 4507 02:55:20,280 --> 02:55:21,880 INFECTIOUS PROTEINOPATHY OF THE 4508 02:55:21,880 --> 02:55:23,400 LUNG. WHAT WE WE ARE GOING TO 4509 02:55:23,400 --> 02:55:25,680 TRY TO EXPRESS IS THE IDEA THAT 4510 02:55:25,680 --> 02:55:27,520 LUNG INFECTION CAN ELICIT 4511 02:55:27,520 --> 02:55:29,800 PRODUCTION OF CYTOTOXIC AMYLOID 4512 02:55:29,800 --> 02:55:32,320 IN THE PARENCHYMA OF THE LUNG 4513 02:55:32,320 --> 02:55:34,080 AND THESE CONTRIBUTE TO END 4514 02:55:34,080 --> 02:55:35,320 ORGAN DYSFUNCTION. WE WILL 4515 02:55:35,320 --> 02:55:37,760 MARROW THIS A BIT FOR PURPOSES 4516 02:55:37,760 --> 02:55:39,760 TODAY FOCUS ON PRODUCTION OF 4517 02:55:39,760 --> 02:55:43,080 CYTOTOXIC VARIANCE OFFER TAU AND 4518 02:55:43,080 --> 02:55:46,000 TALK HOW THOSE VARIANTS OF TAU 4519 02:55:46,000 --> 02:55:47,280 CONTRIBUTE TO NEUROTOXIC 4520 02:55:47,280 --> 02:55:47,960 DYSFUNCTION. 4521 02:55:47,960 --> 02:55:50,080 THIS IS THE INFECTIOUS 4522 02:55:50,080 --> 02:55:51,240 PROTEINOPATHY OF THE LUNG IDEA. 4523 02:55:51,240 --> 02:55:53,040 LET ME START WITH WHAT WE 4524 02:55:53,040 --> 02:55:54,560 LEARNED THE LAST 10, 15 YEARS 4525 02:55:54,560 --> 02:55:57,160 THAT INFORM OUR POSITION OF HOW 4526 02:55:57,160 --> 02:55:59,400 WE THINK ABOUT THIS PROBLEM. THE 4527 02:55:59,400 --> 02:56:00,480 FIRST THING THAT IS REALLY 4528 02:56:00,480 --> 02:56:02,400 IMPORTANT TO UNDERSTAND IS THAT 4529 02:56:02,400 --> 02:56:05,000 LUNG ENDOTHELIAL CELLS EXPRESS 4530 02:56:05,000 --> 02:56:06,560 MICROTUBULE ASSOCIATED PROTEIN 4531 02:56:06,560 --> 02:56:09,320 TAU. SO FOR ABOUT 15 YEARS WE AN 4532 02:56:09,320 --> 02:56:11,640 OTHERS HAVE DISCOVERED THE 4533 02:56:11,640 --> 02:56:14,520 EXPRESSION OF TAU IN CELLS 4534 02:56:14,520 --> 02:56:16,520 ENDOTHELIAL CELLS IN CULTURE AND 4535 02:56:16,520 --> 02:56:18,520 PROVIDE A SIGNIFICANT EVIDENCE 4536 02:56:18,520 --> 02:56:21,280 TOWARD THIS IDEA BASED ON RT PCR 4537 02:56:21,280 --> 02:56:22,400 CLONING WESTERN BLOTTING 4538 02:56:22,400 --> 02:56:24,760 PROTEOMIC ANALYSIS AN FUNCTIONAL 4539 02:56:24,760 --> 02:56:26,320 STUDIES OF MICROTUBULE 4540 02:56:26,320 --> 02:56:27,960 STABILITY. FOR THE MOST PART 4541 02:56:27,960 --> 02:56:29,440 THESE STUDIES OR THESE EARLY 4542 02:56:29,440 --> 02:56:31,320 STUDIES REALLY FOCUSED ON CELL 4543 02:56:31,320 --> 02:56:33,560 CULTURE MODELS AND ONLY RECENTLY 4544 02:56:33,560 --> 02:56:36,080 SORT OF TRANSLATED THIS INTO 4545 02:56:36,080 --> 02:56:37,240 PRE-TRANSLATIONAL MODELS AND 4546 02:56:37,240 --> 02:56:40,600 CLINICAL SETTING. SO THIS IS A 4547 02:56:40,600 --> 02:56:42,040 MOUSE, SIGNIFICANT FOR TAU KNOCK 4548 02:56:42,040 --> 02:56:45,040 OUT WITH INSERTION OF REPORTER 4549 02:56:45,040 --> 02:56:47,280 EGFP AND EXON 1 OF THE MAPT 4550 02:56:47,280 --> 02:56:50,560 GENE. SO IN PRINCIPLE CELL 4551 02:56:50,560 --> 02:56:51,600 EXPRESSING TAU SHOULD BE GREEN. 4552 02:56:51,600 --> 02:56:53,480 SO WITH THIS IN MIND WE PERFORM 4553 02:56:53,480 --> 02:56:56,800 STUDIES TO FULLY RECRUIT THE 4554 02:56:56,800 --> 02:56:58,320 MICROCIRCULATION AND THEN 4555 02:56:58,320 --> 02:57:00,240 SECTIONED LARGE SECTIONS OF THE 4556 02:57:00,240 --> 02:57:02,800 LUNG IMAGED BY MULTI-PHOTON 4557 02:57:02,800 --> 02:57:04,200 IMAGING THROUGH THAT WHOLE 4558 02:57:04,200 --> 02:57:05,120 SECTION AND SO THE FIRST THING 4559 02:57:05,120 --> 02:57:09,480 THAT YOU NOTICE IS THAT IN THIS 4560 02:57:09,480 --> 02:57:11,960 MOUSE, THERE IS EXTENSIVE 4561 02:57:11,960 --> 02:57:14,880 EXPRESSION OF TAU OR EGFP IN THE 4562 02:57:14,880 --> 02:57:16,880 LUNG PARENCHYMA. WHEN YOU LOOK 4563 02:57:16,880 --> 02:57:19,880 MORE CLOSELY AT WHERE IN 4564 02:57:19,880 --> 02:57:21,800 MICROCIRCULATION THAT TAU IS 4565 02:57:21,800 --> 02:57:23,160 EXPRESSED WHAT YOU CAN BEGIN TO 4566 02:57:23,160 --> 02:57:24,440 APPRECIATE IS IN THESE CAPILLARY 4567 02:57:24,440 --> 02:57:27,360 LOOPS. SO IF YOU LOOK ACROSS 4568 02:57:27,360 --> 02:57:29,320 THIS SECTION, WHAT YOU CAN SEE 4569 02:57:29,320 --> 02:57:32,520 VERY CLEARLY HERE IN THESE TWO 4570 02:57:32,520 --> 02:57:33,880 CAPILLARIES THAT ARE HIGHLIGHTED 4571 02:57:33,880 --> 02:57:36,840 ON THIS RIGHT SIDE, THE ADJACENT 4572 02:57:36,840 --> 02:57:38,360 EPITHELIUM SEEMS NEGATIVE FOR 4573 02:57:38,360 --> 02:57:40,400 TAU BUT CAPILLARY ENDOTHELIUM 4574 02:57:40,400 --> 02:57:41,920 SEEMS TO BE QUITE POSITIVE FOR 4575 02:57:41,920 --> 02:57:44,720 TAU EXPRESSING. THIS IDEA WAS 4576 02:57:44,720 --> 02:57:49,520 FURTHER SUPPORTED BY THE MESNER 4577 02:57:49,520 --> 02:57:51,840 GROUPS IN THIS PAPER THEY 4578 02:57:51,840 --> 02:57:53,080 IDENTIFY DIFFERENT ENDOTHELIAL 4579 02:57:53,080 --> 02:57:55,160 ARCHETYPES IN THE CAPILLARY 4580 02:57:55,160 --> 02:57:56,880 PLEXUS OF THE LUNG. THE PRIMARY 4581 02:57:56,880 --> 02:58:01,160 FOCUS ON RESOLVING AEROCYTE AS 4582 02:58:01,160 --> 02:58:03,040 PHENOTYPE OF THE CELL IN THE 4583 02:58:03,040 --> 02:58:03,800 MICROCIRCULATION AS BEING PART 4584 02:58:03,800 --> 02:58:05,080 OF THE ENDOTHELIUM THAT THERE 4585 02:58:05,080 --> 02:58:09,200 WAS ADJACENT TO TYPE 1 4586 02:58:09,200 --> 02:58:11,320 EPITHELIAL CELLS IN THIN PORTION 4587 02:58:11,320 --> 02:58:13,080 OF THE BLOOD GAS BARRIER AN 4588 02:58:13,080 --> 02:58:14,480 GENERAL CAPILLARY MORE ASSOCIATE 4589 02:58:14,480 --> 02:58:17,960 WITH THE THE THICK REGION OF 4590 02:58:17,960 --> 02:58:19,160 BLOOD GAS BARRIER AND 4591 02:58:19,160 --> 02:58:20,160 COMMUNICATING WITH OTHER CELLS 4592 02:58:20,160 --> 02:58:21,840 IN THAT THICK REGION. WHAT THEY 4593 02:58:21,840 --> 02:58:23,640 FOUND OR WHAT THEY SUGGEST WAS 4594 02:58:23,640 --> 02:58:26,160 THE AEROCYTE WAS A LARGER CELL, 4595 02:58:26,160 --> 02:58:31,000 A LARGER CELL IN THE G CAP WAS A 4596 02:58:31,000 --> 02:58:32,400 SMALLER NUMEROUS CELL MOST 4597 02:58:32,400 --> 02:58:34,600 RESPONSIVE TO INJURY AND REPAIR. 4598 02:58:34,600 --> 02:58:37,600 BOTH THESE CELLS WERE ORIGINATED 4599 02:58:37,600 --> 02:58:40,640 FROM A COMMON BIPOTENT 4600 02:58:40,640 --> 02:58:43,160 PROGENITOR CELL AS EARLY AS 4601 02:58:43,160 --> 02:58:44,480 PSEUDOGLANDULAR STAGE OF LUNG 4602 02:58:44,480 --> 02:58:45,480 DEVELOPMENT. WHAT WAS 4603 02:58:45,480 --> 02:58:46,280 INTERESTING TO US IS THEY FOUND 4604 02:58:46,280 --> 02:58:47,680 ONLY A SMALL NUMBER OF GENES 4605 02:58:47,680 --> 02:58:50,080 THAT WERE EXPRESSED IN ALL OF 4606 02:58:50,080 --> 02:58:51,960 THE CAPILLARY ENDOTHELIAL CELLS 4607 02:58:51,960 --> 02:58:55,000 THEY STUDIED. ONE OF THOSE GENES 4608 02:58:55,000 --> 02:58:56,200 EXPRESSED EARLY AND MAYBE 4609 02:58:56,200 --> 02:58:57,960 EARLIER THAN THE PSEUDOGLANDULAR 4610 02:58:57,960 --> 02:58:59,600 STAGE OF LUNG DEVELOPMENT WAS IN 4611 02:58:59,600 --> 02:59:02,720 FACT TAU. FURTHER SUPPORT FOR 4612 02:59:02,720 --> 02:59:04,680 THIS GENERAL IDEA COMES FROM 4613 02:59:04,680 --> 02:59:08,720 THIS SINGLE CELL ATLAS OF THE 4614 02:59:08,720 --> 02:59:10,320 ENDOTHELIUM FROM THE YALE GROUP 4615 02:59:10,320 --> 02:59:12,720 WHERE YOU CAN ARCHETYPE CELL 4616 02:59:12,720 --> 02:59:14,520 PHENOTYPES BASED ON SINGLE CELL 4617 02:59:14,520 --> 02:59:16,480 RNA ANALYSIS. IF YOU 4618 02:59:16,480 --> 02:59:18,280 SPECIFICALLY LOOK AT THE 4619 02:59:18,280 --> 02:59:19,760 ENDOTHELIAL POPULATIONS WITHIN 4620 02:59:19,760 --> 02:59:22,800 THOSE ARCHETYPES YOU SEE HERE 4621 02:59:22,800 --> 02:59:24,920 THE AEROCYTE POPULATION AND 4622 02:59:24,920 --> 02:59:27,040 GENERAL CAPILLARY POPULATION, 4623 02:59:27,040 --> 02:59:28,240 YOU CAN QUANTIFY THAT AND YOU 4624 02:59:28,240 --> 02:59:30,200 CAN SEE IN FACT THE TAU IS 4625 02:59:30,200 --> 02:59:33,280 HIGHLY EXPRESSED IN THE LUNG 4626 02:59:33,280 --> 02:59:34,880 MICROCIRCULATION MORE SO THAN IN 4627 02:59:34,880 --> 02:59:37,160 OTHER KINDS OF ENDOTHELIAL CELLS 4628 02:59:37,160 --> 02:59:40,360 INCLUDING ARTERIAL VENOUS 4629 02:59:40,360 --> 02:59:41,600 BRONCHIAL AND LYMPHATIC 4630 02:59:41,600 --> 02:59:43,520 ENDOTHELIAL CELLS SO LOOKS CLEAR 4631 02:59:43,520 --> 02:59:45,200 THAT TAU IS EXPRESSED IN THE 4632 02:59:45,200 --> 02:59:47,960 LUNG MICROCIRCULATION. AND THEN 4633 02:59:47,960 --> 02:59:52,600 MOST RECENTLY CHOW AND LYNN HAVE 4634 02:59:52,600 --> 02:59:55,120 CLONED THE LUNG ENDOTHELIAL TAU 4635 02:59:55,120 --> 02:59:57,120 BOTH FROM LUNG ITSELF AND THEN 4636 02:59:57,120 --> 02:59:59,920 FROM ENDOTHELIUM. THEY CLONED AT 4637 02:59:59,920 --> 03:00:01,760 LEAST FOUR ISOFORMS AT THE 4638 03:00:01,760 --> 03:00:05,360 ENDOTHELIAL TAU INCLUDING SO 4639 03:00:05,360 --> 03:00:09,600 CALLED ZERO IN O ALREADY 1N 4R 4640 03:00:09,600 --> 03:00:12,360 2N 4R TAU, THESE ARE TAUS 4641 03:00:12,360 --> 03:00:13,960 PREVIOUSLY KNOWN TO BE IN THE 4642 03:00:13,960 --> 03:00:15,480 CENTRAL NERVOUS SYSTEM AND THEY 4643 03:00:15,480 --> 03:00:17,840 IDENTIFIED A BIG TAU WHICH IS A 4644 03:00:17,840 --> 03:00:21,280 TAU ISOFORM THAT IS PROMINENT IN 4645 03:00:21,280 --> 03:00:23,000 PERIPHERAL NERVES. WHAT IS 4646 03:00:23,000 --> 03:00:24,920 NOTABLE IS ALL FOUR OF THESE 4647 03:00:24,920 --> 03:00:26,720 ISOFORMS POSSESS A CONSERVED 4648 03:00:26,720 --> 03:00:28,600 REGION IN THE MICROTUBULE 4649 03:00:28,600 --> 03:00:32,040 BINDING DOMAINS OF THIS TAU. 4650 03:00:32,040 --> 03:00:33,960 THESE TWO CONSERVE SEQUENCES ARE 4651 03:00:33,960 --> 03:00:35,120 SO CALLED AGGREGATION DOMAINS 4652 03:00:35,120 --> 03:00:37,880 AND THOSE ARE KNOWN TO BE 4653 03:00:37,880 --> 03:00:39,640 MECHANISTICALLY INVOLVED IN 4654 03:00:39,640 --> 03:00:41,960 PRODUCTION OF CYTOTOXIC VARIANTS 4655 03:00:41,960 --> 03:00:43,760 OF TAU CHRONIC NEURODEGENERATIVE 4656 03:00:43,760 --> 03:00:46,160 DISEASE. SO THE TEACHING POINTS 4657 03:00:46,160 --> 03:00:47,600 FROM THIS FIRST SECTION HERE IS 4658 03:00:47,600 --> 03:00:49,440 THAT LUNG CAPILLARY ENDOTHELIAL 4659 03:00:49,440 --> 03:00:51,840 CELLS INCLUDING AEROCYTE AND 4660 03:00:51,840 --> 03:00:54,040 GENERAL CAPILLARY CELLS, IN THE 4661 03:00:54,040 --> 03:00:56,600 LUNG EXPRESS TAU AND AT LEAST 4662 03:00:56,600 --> 03:00:58,720 ONE OF THE FUNCTION OF THESE TAU 4663 03:00:58,720 --> 03:01:02,280 OF THESE TAU ISOFORMS IS TO 4664 03:01:02,280 --> 03:01:04,600 STABILIZE MICROTUBULES. SO FIRST 4665 03:01:04,600 --> 03:01:06,400 THING WE KNOW IS ENDOTHELIAL 4666 03:01:06,400 --> 03:01:08,200 CELLS IN THE LUNG PARENCHYMA 4667 03:01:08,200 --> 03:01:09,760 HAVE A TAU. WHAT WE HAVE ALSO 4668 03:01:09,760 --> 03:01:11,680 LEARNED IS THAT LOWER 4669 03:01:11,680 --> 03:01:13,000 RESPIRATORY TRACK INFECTION 4670 03:01:13,000 --> 03:01:14,240 DRIVES THE PRODUCTION OF TAU 4671 03:01:14,240 --> 03:01:17,000 VARIANTS THAT ARE CYTOTOXIC. SO 4672 03:01:17,000 --> 03:01:19,000 WHEN YOU HAVE A LOWER 4673 03:01:19,000 --> 03:01:21,000 RESPIRATORY TRACK INFECTION WE 4674 03:01:21,000 --> 03:01:22,960 OBSERVE THE PHOSPHORYLATION OF 4675 03:01:22,960 --> 03:01:24,840 THESE TAU VARIANTS. AND WHEN 4676 03:01:24,840 --> 03:01:26,720 THESE TAU VARIANTS BECOME 4677 03:01:26,720 --> 03:01:28,480 PHOSPHORYLATED THEY ACQUIRE 4678 03:01:28,480 --> 03:01:29,960 UNUSUAL PHYSICAL CHEMICAL 4679 03:01:29,960 --> 03:01:31,680 PROPERTIES THAT AS THEY ARE EACH 4680 03:01:31,680 --> 03:01:33,880 STABLE, THEY ARE RHESUS TENT TO 4681 03:01:33,880 --> 03:01:35,560 PROTEASES, -- RESISTANT TO 4682 03:01:35,560 --> 03:01:37,120 PROTEASES TRANSMISSIBLE FROM ONE 4683 03:01:37,120 --> 03:01:39,000 CELL TO ANOTHER ONE ORGAN TO 4684 03:01:39,000 --> 03:01:40,280 ANOTHER TO FROM ONE ANIMAL TO 4685 03:01:40,280 --> 03:01:45,200 ANOTHER AND ACROSS SPECIES AND 4686 03:01:45,200 --> 03:01:48,200 SELF-REPLY REPLICATE -- REPLY 4687 03:01:48,200 --> 03:01:50,280 SATING. MISVARIANT FORM OF TAU 4688 03:01:50,280 --> 03:01:51,840 CAN DRIVE THE NEW CYTOTOXIC 4689 03:01:51,840 --> 03:01:54,040 VARIANTS IN OTHERWISE UNINFECTED 4690 03:01:54,040 --> 03:01:56,800 NAIVE CELLS. THESE BECOME SIGH 4691 03:01:56,800 --> 03:01:58,480 TOY TOXIC. YOU WILL RECOGNIZE 4692 03:01:58,480 --> 03:02:02,560 THIS AS BEING A FREION LIKE 4693 03:02:02,560 --> 03:02:05,240 PHENOMENON, KEEP STABLE PROTEASE 4694 03:02:05,240 --> 03:02:06,960 RESISTANT TRANSMISSIBLE 4695 03:02:06,960 --> 03:02:08,360 SELF-REPLICATING AND CYTOTOXIC. 4696 03:02:08,360 --> 03:02:11,960 SO PNEUMONIA LOWER RESPIRATORY 4697 03:02:11,960 --> 03:02:15,080 TRACT INFECTION IS INITIATING A 4698 03:02:15,080 --> 03:02:17,960 FREION LIKE PHENOMENON. STUDIES 4699 03:02:17,960 --> 03:02:21,800 FOCUS ON PSEUDOMONAS AEROGINOSA. 4700 03:02:21,800 --> 03:02:24,200 ONE THING THAT IS EXTREMELY 4701 03:02:24,200 --> 03:02:26,400 IMPORTANT, NOT ALL VARIANTS OR 4702 03:02:26,400 --> 03:02:32,600 STRAINS OF PSEUDOMONAS DO THIS. 4703 03:02:32,600 --> 03:02:34,400 THE CHRONICALLY COLONIZING 4704 03:02:34,400 --> 03:02:36,280 AIRWAYS IN CYSTIC FIBROSIS 4705 03:02:36,280 --> 03:02:37,240 PATIENTS DON'T HAVE TYPE 3 4706 03:02:37,240 --> 03:02:40,280 SECRETION SYSTEM AND DON'T DRIVE 4707 03:02:40,280 --> 03:02:41,800 THIS PHENOMENON. IN STARK 4708 03:02:41,800 --> 03:02:43,800 CONTRAST DISSEMINATED VARIANTS 4709 03:02:43,800 --> 03:02:45,800 OF PSEUDOMOW IN THIS THAT 4710 03:02:45,800 --> 03:02:47,480 UPREGULATE THE TYPE 3 SECRETION 4711 03:02:47,480 --> 03:02:48,840 SYSTEM DRIVE THIS PHENOMENON. WE 4712 03:02:48,840 --> 03:02:50,320 HAVE LEARNED ABOUT THE 4713 03:02:50,320 --> 03:02:53,880 MECHANISMS BY WHICH THIS WORKS. 4714 03:02:53,880 --> 03:02:55,960 THE PSEUDOMONAS TYPE 3 SECRETION 4715 03:02:55,960 --> 03:02:59,440 SYSTEM INTRODUCES EXO ENZYMES TO 4716 03:02:59,440 --> 03:03:01,400 THE HOST CELL AND SOME OF THESE 4717 03:03:01,400 --> 03:03:03,200 ENZYMES DRIVE THE HOST CELL 4718 03:03:03,200 --> 03:03:05,040 KINASE ACTIVITY THAT CAN CAUSE 4719 03:03:05,040 --> 03:03:10,440 TAU PHOSPHORYLATION AND 4720 03:03:10,440 --> 03:03:12,400 CONCURRENTLY DIS DISASSEMBLE OR 4721 03:03:12,400 --> 03:03:14,480 REORGANIZE MICROTUBULES 4722 03:03:14,480 --> 03:03:15,760 CONTRIBUTING TO 4723 03:03:15,760 --> 03:03:18,520 HYPERPERMEABILITY. WHEN THE TYPE 4724 03:03:18,520 --> 03:03:20,160 3 SECRETION SYSTEM EFFECTORS 4725 03:03:20,160 --> 03:03:22,480 TARGET THE LUNG MICROGENERATION, 4726 03:03:22,480 --> 03:03:24,240 THEY GENERATE VARIANTS OF TAU 4727 03:03:24,240 --> 03:03:26,440 RELEASED TO THE PERIPHERY AND 4728 03:03:26,440 --> 03:03:30,680 THEY BREAK DOWN MICROTUBULES 4729 03:03:30,680 --> 03:03:33,200 THAT BREAK DOWN THE ALVEOLAR 4730 03:03:33,200 --> 03:03:35,880 CAPILLARY BARRIER. NOTABLY, THE 4731 03:03:35,880 --> 03:03:37,480 CYTOTOXIC OR TAU VARIANTS 4732 03:03:37,480 --> 03:03:39,320 RELEASED FROM THE ENDOTHELIUM 4733 03:03:39,320 --> 03:03:42,000 ARE IN FACT CYTOTOXIC TO 4734 03:03:42,000 --> 03:03:46,480 OTHERWISE NAIVE CELLS. SO ONE OF 4735 03:03:46,480 --> 03:03:47,800 THE EXOENZYMES TO HIGHLIGHT FOR 4736 03:03:47,800 --> 03:03:48,920 REFERENCE TO COME BACK TO THIS 4737 03:03:48,920 --> 03:03:53,680 IS THIS EXOENZYME CALLED Y. THIS 4738 03:03:53,680 --> 03:03:57,560 IS A PROMISE PROMISE PROMISE 4739 03:03:57,560 --> 03:03:59,440 PRO-- PROMISE PROMISCUOUS 4740 03:03:59,440 --> 03:04:02,360 CYCLASE IN ABSENCE OF THAT CUREA 4741 03:04:02,360 --> 03:04:05,040 TO DRIVE TAU PHOSPHORYLATION. 4742 03:04:05,040 --> 03:04:07,600 THIS CYTOTOXIC VARIANTS OF TAU 4743 03:04:07,600 --> 03:04:11,280 ARE POWERFUL IF WE IMMUNOISOLATE 4744 03:04:11,280 --> 03:04:13,840 AFTER INFECTION AND PUT ON NAIVE 4745 03:04:13,840 --> 03:04:14,920 CELLS WHAT YOU CAN SEE IN 24 4746 03:04:14,920 --> 03:04:17,000 HOUR MOVIE COMPRESS IS WITHIN 4747 03:04:17,000 --> 03:04:18,760 SIX TO EIGHT HOURS THE CELLS 4748 03:04:18,760 --> 03:04:20,840 WILL UNDERGO CYTOTOXIC RESPONSE. 4749 03:04:20,840 --> 03:04:22,880 SO THIS IS A VERY PROFOUND 4750 03:04:22,880 --> 03:04:28,640 EFFECT, NOT SUBTLE AT ALL. THE 4751 03:04:28,640 --> 03:04:30,560 CYTOTOXIC VARIANTS ARE PRODUCED 4752 03:04:30,560 --> 03:04:38,360 BY PSEUDOMONAS EARGENOSA LIKE XO 4753 03:04:38,360 --> 03:04:41,280 Y BUT NOT LIKE IT BUT INCLUDING 4754 03:04:41,280 --> 03:04:43,960 XOY. WE HAVE SEEN THIS ACROSS 4755 03:04:43,960 --> 03:04:46,640 MULTITUDE OF ORGANISMS 4756 03:04:46,640 --> 03:04:50,000 PHENOMENON OF CYTOTOXIC 4757 03:04:50,000 --> 03:04:55,920 ENDOTHELIUM LIKE MRSA CLUB SEAL 4758 03:04:55,920 --> 03:04:59,680 CLUB SEE YELL -- IN OTHER CASES 4759 03:04:59,680 --> 03:05:01,560 ABOUT THE VIRULENCE ARSENAL 4760 03:05:01,560 --> 03:05:02,880 THESE ORGANISMS ARE USING TO 4761 03:05:02,880 --> 03:05:04,560 DRIVE THE CYTOTOXIC TAU 4762 03:05:04,560 --> 03:05:06,000 PRODUCTION. SO THE SECONDS THING 4763 03:05:06,000 --> 03:05:07,960 WE HAVE LEARNED IS THAT BOTH 4764 03:05:07,960 --> 03:05:09,720 GRAM POSITIVE AND NEGATIVE 4765 03:05:09,720 --> 03:05:13,640 MICROORGANISMS ELICIT CYTOTOXIC 4766 03:05:13,640 --> 03:05:14,800 TAU PRODUCTION AND WE HAVE SEEN 4767 03:05:14,800 --> 03:05:15,960 IT IN VIRAL INFECTION AND WE CAN 4768 03:05:15,960 --> 03:05:18,480 TALK ABOUT THIS MORE LATER. 4769 03:05:18,480 --> 03:05:20,240 IMPORTANTLY THE VIRULENCE 4770 03:05:20,240 --> 03:05:23,160 ARSENAL THAT IS USED BY THESE 4771 03:05:23,160 --> 03:05:24,560 MICROORGANISMS IS ESSENTIAL FOR 4772 03:05:24,560 --> 03:05:26,480 DRIVING THE INTERKINGDOM OF 4773 03:05:26,480 --> 03:05:27,480 COMMUNICATION THAT CULMINATES IN 4774 03:05:27,480 --> 03:05:29,120 THE PRODUCTION OF THIS CYTOTOXIC 4775 03:05:29,120 --> 03:05:32,880 TAU VARIANTS. SO WE KNOW THE 4776 03:05:32,880 --> 03:05:34,520 LUNG ENDOTHELIUM HAS TAU. WE 4777 03:05:34,520 --> 03:05:36,920 KNOW INFECTION CAN DRIVE 4778 03:05:36,920 --> 03:05:40,640 CYTOTOXIC TAU VARIANTS THAT CAN 4779 03:05:40,640 --> 03:05:42,560 BE DELETERIOUS. WHERE DOES IT 4780 03:05:42,560 --> 03:05:45,240 GO? WHAT WE KNOW FROM STUDIES IS 4781 03:05:45,240 --> 03:05:46,680 WHEN CYTOTOXIC TAU IS GENERATED 4782 03:05:46,680 --> 03:05:48,360 IN THE NATURAL COURSE OF 4783 03:05:48,360 --> 03:05:51,040 INFECTION, IT CAN BE RECOVERED 4784 03:05:51,040 --> 03:05:55,000 FROM THE LAVAGE FLUID, BLOOD, 4785 03:05:55,000 --> 03:05:57,720 HEART, CEREBRAL SPINAL FLUID AND 4786 03:05:57,720 --> 03:05:59,040 BRAIN PARENCHYMA. SO A LITTLE 4787 03:05:59,040 --> 03:06:01,800 BIT ON THIS, IF WE LOOK AT 4788 03:06:01,800 --> 03:06:03,400 ALVEOLAR LAVAGE FLUID FIRST, 4789 03:06:03,400 --> 03:06:04,840 LET'S HIGHLIGHT THIS EXPERIMENT, 4790 03:06:04,840 --> 03:06:08,640 THIS STUDY THAT WAS DONE WITH 4791 03:06:08,640 --> 03:06:12,920 OUR COLLEAGUES AT UAB AND RON 4792 03:06:12,920 --> 03:06:15,800 HERE ALSO AT UNIVERSITY. WHICH 4793 03:06:15,800 --> 03:06:19,040 WE STUDIED EIGHT PATIENTS FOUR 4794 03:06:19,040 --> 03:06:22,040 WHOM HAD ONGOING LOWER 4795 03:06:22,040 --> 03:06:23,800 RESPIRATORY TRACK INFECTION AND 4796 03:06:23,800 --> 03:06:26,400 FOUR WHOM DIDN'T. ALL EIGHT 4797 03:06:26,400 --> 03:06:28,240 PATIENTS HAD SIMILAR SOFA SCORES 4798 03:06:28,240 --> 03:06:32,520 AND THEY WERE MEDICALLY 4799 03:06:32,520 --> 03:06:34,400 CLINICALLY INTERESTING BECAUSE 4800 03:06:34,400 --> 03:06:36,560 THEY HAD WRONG CLEO LAR LAVAGE 4801 03:06:36,560 --> 03:06:38,840 FLUID AND CSF FROM THE SAME 4802 03:06:38,840 --> 03:06:41,920 PATIENT. WHEN RON DID THE 4803 03:06:41,920 --> 03:06:46,000 WESTERN BLOTTING OF THE BRONC 4804 03:06:46,000 --> 03:06:47,320 OWE LAR LAVAGE FLUID HE 4805 03:06:47,320 --> 03:06:48,640 IMMUNOPRE PRECIPITATED WITH 4806 03:06:48,640 --> 03:06:51,400 AMYLOID ANTIBODY CALLED A 11 AND 4807 03:06:51,400 --> 03:06:53,520 IMMUNOBLOTTED WITH TNT 1 4808 03:06:53,520 --> 03:06:55,000 ANTI-TAU ANTIBODY. AND WHAT YOU 4809 03:06:55,000 --> 03:06:57,760 SEE IS THAT IN THE BALF OF THE 4810 03:06:57,760 --> 03:07:00,960 FOUR PATIENTS ALL HAD PROMINENT 4811 03:07:00,960 --> 03:07:04,160 TAU IMMUNOREACTIVE BANNING, 4812 03:07:04,160 --> 03:07:05,600 WHEREAS THE PATIENTS THAT DID 4813 03:07:05,600 --> 03:07:07,720 NOT HAVE ONGOING INFECTION HAD 4814 03:07:07,720 --> 03:07:11,000 ONLY MINOR OR NO TAU 4815 03:07:11,000 --> 03:07:20,240 IMMUNOREACTIVITY. WE CAN FOLLOW 4816 03:07:20,240 --> 03:07:23,600 THIS PATTERN SYSTEMATICALLY IN 4817 03:07:23,600 --> 03:07:25,680 PNEUMONIA MODEL. REINFECT 4818 03:07:25,680 --> 03:07:28,200 RODENTS WITH PSEUDO PSEUDOMONAS. 4819 03:07:28,200 --> 03:07:30,120 WE STUDY RESPONSE TO INFECTION 4820 03:07:30,120 --> 03:07:32,240 AND COLLECT ARTERIAL PLASMA FOR 4821 03:07:32,240 --> 03:07:35,680 ANALYSIS. THIS IS AN EXAMPLE OF 4822 03:07:35,680 --> 03:07:37,560 THE KIND OF TAU IMMUNOREACTIVE 4823 03:07:37,560 --> 03:07:39,120 BANDING WE SEE IN THE PLASMA, 4824 03:07:39,120 --> 03:07:42,760 THE HEART AND THE BRAIN IN THESE 4825 03:07:42,760 --> 03:07:48,720 ANIMALS AFTER INFECTION. SO WE 4826 03:07:48,720 --> 03:07:51,720 KNOW THAT WHEN WE HAVE INFECTION 4827 03:07:51,720 --> 03:07:52,960 CYTOTOXIC TAU VARIANTS ARE 4828 03:07:52,960 --> 03:07:54,400 GENERATED AND THEY ARE PRESENT 4829 03:07:54,400 --> 03:07:56,360 IN THE BALF, THE PLASMA, THE 4830 03:07:56,360 --> 03:08:00,440 HEART AND THE BRAIN OF BOTH 4831 03:08:00,440 --> 03:08:03,160 ANIMAL AND HUMAN SUBJECTS WITH 4832 03:08:03,160 --> 03:08:08,560 ONGOING PNEUMONIA, AND TAU DISIS 4833 03:08:08,560 --> 03:08:09,920 ASSOCIATED WITH END ORGAN 4834 03:08:09,920 --> 03:08:11,480 DYSFUNCTION. THE BALF 4835 03:08:11,480 --> 03:08:13,440 CONCENTRATIONS OF T 22 4836 03:08:13,440 --> 03:08:15,880 IMMUNOACTIVE TAU ARE HIGHLY 4837 03:08:15,880 --> 03:08:18,080 ASSOCIATED WITH THE FOUR POINT 4838 03:08:18,080 --> 03:08:20,000 LUNG INJURY SCORE AMONG OTHER 4839 03:08:20,000 --> 03:08:21,000 INDICES OF END ORGAN 4840 03:08:21,000 --> 03:08:25,440 DYSFUNCTION. SO WE GENERATE 4841 03:08:25,440 --> 03:08:27,400 CYTOTOXIC VARIANTS OF TAU, THIS 4842 03:08:27,400 --> 03:08:31,400 TAU CAN DISSEMINATE INTO VARIOUS 4843 03:08:31,400 --> 03:08:33,800 BIOCOMPARTMENTS AND IT CAN BE 4844 03:08:33,800 --> 03:08:35,000 INJURIOUS. WHAT HAPPENS WHEN IT 4845 03:08:35,000 --> 03:08:36,840 GETS TO THE BRAIN? SO WHAT WE 4846 03:08:36,840 --> 03:08:38,840 HAVE LEARNED OVER THE YEARS IS 4847 03:08:38,840 --> 03:08:41,600 THAT THE INFECTION ELICITED 4848 03:08:41,600 --> 03:08:42,800 CYTOTOXIC TAU VARIANTS ARE 4849 03:08:42,800 --> 03:08:44,440 DELETERIOUS TO THE HIPPOCAMPUS. 4850 03:08:44,440 --> 03:08:47,000 THEY CAN INHIBIT LONG TERM 4851 03:08:47,000 --> 03:08:48,880 POTENTIATION, CAUSE 4852 03:08:48,880 --> 03:08:50,440 HYPEREXCITABILITY AND OVER TIME 4853 03:08:50,440 --> 03:08:51,960 CAN REDUCE SPINE DENSITY MANY 4854 03:08:51,960 --> 03:08:56,160 THE CA 1 NEURONS. -- IN THE CA 1 4855 03:08:56,160 --> 03:08:58,040 NEURONS. BACK TO THE STUDY WE 4856 03:08:58,040 --> 03:09:01,160 PERFORMED WITH THESE EIGHT 4857 03:09:01,160 --> 03:09:02,760 PATIENTS, AND NOW LET'S EXAMINE 4858 03:09:02,760 --> 03:09:06,400 WORK THAT WAS DONE BY 4859 03:09:06,400 --> 03:09:07,400 NEUROSCIENTIST MIKE LYNN WITH 4860 03:09:07,400 --> 03:09:09,840 THE CSF OBTAINED FROM THESE 4861 03:09:09,840 --> 03:09:11,000 PATIENTS. SO I JUST WANT TO 4862 03:09:11,000 --> 03:09:13,040 POINT OUT WHEN THE CSF WAS 4863 03:09:13,040 --> 03:09:16,120 OBTAINED IT WAS BOILED OR NOT 4864 03:09:16,120 --> 03:09:18,600 BOILED BEFORE IT WAS STUDIED. 4865 03:09:18,600 --> 03:09:21,560 AND THIS ALLOWED US TO 4866 03:09:21,560 --> 03:09:23,480 INACTIVATE HEAT SENSITIVE HEAT 4867 03:09:23,480 --> 03:09:25,120 LAY BILE MOLECULES AND STUDY 4868 03:09:25,120 --> 03:09:27,840 ONLY HEAT STABLE MOLECULES AND 4869 03:09:27,840 --> 03:09:29,120 COMPARE THEM. WHAT MIKE DID IS 4870 03:09:29,120 --> 03:09:32,800 TOOK THE CSF AND INCUBATED ON 4871 03:09:32,800 --> 03:09:34,200 HIPPOCAMPAL SLICES FROM RODENTS 4872 03:09:34,200 --> 03:09:35,400 AND EXAMINED LONG TERM 4873 03:09:35,400 --> 03:09:38,120 POTENTIATION. SO ON THE Y AXIS 4874 03:09:38,120 --> 03:09:41,120 HERE WHAT WE HAVE IS THE FIELD 4875 03:09:41,120 --> 03:09:42,680 POTENTIAL, FIELD EXCITATORY POST 4876 03:09:42,680 --> 03:09:44,360 SYNAPTIC POTENTIALIAL PLOTTED 4877 03:09:44,360 --> 03:09:46,440 AGAINST TIME AND THE RESPONSE IN 4878 03:09:46,440 --> 03:09:49,400 THIS CASE WAS TO HIGH FREQUENCY 4879 03:09:49,400 --> 03:09:51,400 STIMULATION. AND THE WHITE 4880 03:09:51,400 --> 03:09:54,600 CIRCLES AT THE TOP REPRESENT THE 4881 03:09:54,600 --> 03:09:56,960 LTP LONG TERM POTENTIAL THAT WAS 4882 03:09:56,960 --> 03:10:00,440 OBSERVED IN THE HIPPOCAMPUS 4883 03:10:00,440 --> 03:10:02,720 AFTER THE RODENT HIPPOCAMPUS WAS 4884 03:10:02,720 --> 03:10:05,560 INQUEUE INCUBATED WITH CSF FROM 4885 03:10:05,560 --> 03:10:06,320 THE NON-INFECTED PATIENT. 4886 03:10:06,320 --> 03:10:08,160 REMEMBER THIS PATIENT HAD THE 4887 03:10:08,160 --> 03:10:12,000 SAME APACHE SCORES AN SOFA 4888 03:10:12,000 --> 03:10:13,800 SCORES WITH THE INFECTION. 4889 03:10:13,800 --> 03:10:15,640 HOWEVER, WHEN THE CSF OBTAINED 4890 03:10:15,640 --> 03:10:18,240 FROM THE PATIENT WITH PNEUMONIA 4891 03:10:18,240 --> 03:10:19,960 PATIENTS WITH PNEUMONIA 4892 03:10:19,960 --> 03:10:22,640 INCUBATED ON HIPPOCAMPUS, LTP 4893 03:10:22,640 --> 03:10:26,120 WAS ALTOGETHER ABOLISHED. WE 4894 03:10:26,120 --> 03:10:31,280 THEN NEUTRALIZED THAT CSF WITH 4895 03:10:31,280 --> 03:10:33,600 AN ANTI-TAU ANTIBODY, T 22 4896 03:10:33,600 --> 03:10:35,000 ANTIBODY AND REPEATED 4897 03:10:35,000 --> 03:10:37,360 EXPERIMENT. WHAT YOU SEE IS THAT 4898 03:10:37,360 --> 03:10:39,360 WHEN THE PNEUMONIA PATIENTS CSF 4899 03:10:39,360 --> 03:10:43,360 WAS NEUTRALIZED WITH ANTI-TAU 4900 03:10:43,360 --> 03:10:45,520 ANTIBODY, THE LONG TERM 4901 03:10:45,520 --> 03:10:48,440 POTENTIATION WAS ENTIRELY 4902 03:10:48,440 --> 03:10:53,960 RECOVERED. SO WE CAN FOLLOW THIS 4903 03:10:53,960 --> 03:10:55,920 PROCESS IN PRE-CLINICAL MODELS 4904 03:10:55,920 --> 03:10:57,480 OF PNEUMONIA, WE CAN ADDRESS 4905 03:10:57,480 --> 03:10:59,960 TIME LINE AND SENSITIVITY WITH E 4906 03:10:59,960 --> 03:11:01,200 SEE IN THE BRAIN FOLLOWING 4907 03:11:01,200 --> 03:11:04,400 PNEUMONIA INFECTION. SO FIRST 4908 03:11:04,400 --> 03:11:06,760 QUESTION DOES PNEUMONIA SUPPRESS 4909 03:11:06,760 --> 03:11:08,880 LONG TERM POTENTIATION? TO 4910 03:11:08,880 --> 03:11:12,280 ADDRESS THE ISSUE WE USED 4911 03:11:12,280 --> 03:11:14,520 INTRATRAINIAL INOCULATION OF 4912 03:11:14,520 --> 03:11:16,160 PSEUDOMONAS AND STUDIED 24 AND 4913 03:11:16,160 --> 03:11:21,720 48 HOURS LATER. YOU CAN SEE OVER 4914 03:11:21,720 --> 03:11:23,000 24 AND 48 HOURS THERE IS 4915 03:11:23,000 --> 03:11:26,240 PROGRESSIVE DECLINE IN LONG TERM 4916 03:11:26,240 --> 03:11:27,680 POTENTIATION. THIS IS NOTABLE 4917 03:11:27,680 --> 03:11:29,280 FOR US BECAUSE IT MAKES US THINK 4918 03:11:29,280 --> 03:11:31,800 WE MIGHT HAVE A THERAPEUTIC 4919 03:11:31,800 --> 03:11:35,920 WINDOW IN THE EARLY ADVANCE UPON 4920 03:11:35,920 --> 03:11:38,840 INFECTION. IN ADDITION OVER THE 4921 03:11:38,840 --> 03:11:41,400 SAME TIME COURSE WHAT WE SEE IS 4922 03:11:41,400 --> 03:11:43,680 THAT THE CA 1 VIRUS IS 4923 03:11:43,680 --> 03:11:44,960 HYPEREXCITABLE AS ILLUSTRATED BY 4924 03:11:44,960 --> 03:11:48,920 THE RED LINE HERE IN THE POST 4925 03:11:48,920 --> 03:11:51,240 PSEUDOMONAS INFECTION PERIOD. 4926 03:11:51,240 --> 03:11:52,200 WHEN MIKE STUDIED ORGANIZATION 4927 03:11:52,200 --> 03:11:55,040 OF THE ARCHITECTURE OF THE SPINE 4928 03:11:55,040 --> 03:11:59,120 DENSITY, 1, 2, 3, 4 WEEKS AFTER 4929 03:11:59,120 --> 03:12:01,160 PNEUMONIA, WHAT HE FOUND SUDS 4930 03:12:01,160 --> 03:12:04,520 SIGNIFICANT REDUCTION IN NOT 4931 03:12:04,520 --> 03:12:05,960 ONLY WAS SIGNIFICANT REDUCTION 4932 03:12:05,960 --> 03:12:08,080 IN KINDS OF SPINES PRESENT IN CA 4933 03:12:08,080 --> 03:12:09,680 1 FIBERS. SO OVER TIME A 4934 03:12:09,680 --> 03:12:11,080 SIGNIFICANT REMODELING OF SPINE 4935 03:12:11,080 --> 03:12:12,400 DENSITY WE SEE IN THE 4936 03:12:12,400 --> 03:12:19,160 HIPPOCAMPUS. SO THAT IS 4937 03:12:19,160 --> 03:12:20,920 INTERESTING HOW IMPORTANT 4938 03:12:20,920 --> 03:12:23,040 PSEUDOMONAS -- OR PNEUMONIA IS 4939 03:12:23,040 --> 03:12:24,840 TO DRIVING COGNITIVE 4940 03:12:24,840 --> 03:12:27,360 DISFUNCTION. WHAT ROLE DOES TAU 4941 03:12:27,360 --> 03:12:29,400 LAW? WE REPEAT EXPERIMENTS IN 4942 03:12:29,400 --> 03:12:30,800 WILD TYPE AND TAU KNOCKOUT MICE 4943 03:12:30,800 --> 03:12:33,760 IF WE JUST TAKE A LOOK AT THE 4944 03:12:33,760 --> 03:12:35,440 BLACK CIRCLES HERE THIS IS THE 4945 03:12:35,440 --> 03:12:39,880 WHY WOULD TYPE LTP WE SEE BEFORE 4946 03:12:39,880 --> 03:12:42,000 PNEUMONIA, THEN THE OPEN CIRCLES 4947 03:12:42,000 --> 03:12:44,240 DOWN HERE AFTER PNEUMONIA, WILD 4948 03:12:44,240 --> 03:12:46,160 TYPE MICE ARE SENSITIVE TO 4949 03:12:46,160 --> 03:12:49,240 PNEUMONIA INDUCED REDUCTION IN 4950 03:12:49,240 --> 03:12:51,560 LTP. YOU SEE THE BLACK SQUARES 4951 03:12:51,560 --> 03:12:53,240 REPRESENT TAU KNOCKOUT MICE, 4952 03:12:53,240 --> 03:12:56,280 THEIR LTP IS NORMAL AND STILL 4953 03:12:56,280 --> 03:12:57,480 NORMAL AFTER INFECTION SO THERE 4954 03:12:57,480 --> 03:12:59,640 IS A TAU REQUIREMENT HERE THE 4955 03:12:59,640 --> 03:13:00,640 SUMMARY DATA ARE HIGHLIGHTED 4956 03:13:00,640 --> 03:13:05,600 HERE. UP B NEXT LOCK TERM 4957 03:13:05,600 --> 03:13:08,120 POTENTIATION INDUCES 4958 03:13:08,120 --> 03:13:10,240 HYPEREXCITABILITY AND REDUCES 4959 03:13:10,240 --> 03:13:13,280 SPINE DENSITY IN THE HIPPOCAMPUS 4960 03:13:13,280 --> 03:13:15,080 AND THERE IS TAU RELIANCE IN 4961 03:13:15,080 --> 03:13:15,880 THIS PHENOMENON. WE WERE ASKED 4962 03:13:15,880 --> 03:13:17,080 TO ADDRESS THE QUESTIONS IN 4963 03:13:17,080 --> 03:13:18,520 TERMS OF HOW THE STUDIES WE HAVE 4964 03:13:18,520 --> 03:13:20,720 DONE INFORM OUR POSITION FOR OUR 4965 03:13:20,720 --> 03:13:23,880 OPINION AND IDEAS ABOUT BRAIN 4966 03:13:23,880 --> 03:13:26,000 INJURY AND ARDS, ONE OF THE 4967 03:13:26,000 --> 03:13:26,680 QUESTIONS, DO YOU BELIEVE THERE 4968 03:13:26,680 --> 03:13:29,480 IS A COMMON FINAL PATHWAY FOR 4969 03:13:29,480 --> 03:13:31,440 BRAIN INJURY IN ARDS. SO BASED 4970 03:13:31,440 --> 03:13:34,800 ON WHAT WE DISCUSS CYTOTOXIC TAU 4971 03:13:34,800 --> 03:13:38,760 VARIANTS ARE LISTED BY 4972 03:13:38,760 --> 03:13:41,760 MICROORGANISMS THE VIR LANCE 4973 03:13:41,760 --> 03:13:43,120 ARSENAL IS IMPORTANT TO INITIATE 4974 03:13:43,120 --> 03:13:44,240 THE TAUOPATHY AND WHAT WE HAVE 4975 03:13:44,240 --> 03:13:46,080 SEEN TO THIS POINT STERILE 4976 03:13:46,080 --> 03:13:47,680 INFLAMMATION HAS NOT BEEN ABLE 4977 03:13:47,680 --> 03:13:49,800 OR SUFFICIENT TO ELICIT THE 4978 03:13:49,800 --> 03:13:51,280 PRODUCTION OF CYTOTOXIC TAU 4979 03:13:51,280 --> 03:13:52,960 VARIANTS. SO WHEN WE THINK ABOUT 4980 03:13:52,960 --> 03:13:55,880 QUESTION LIKE THIS, WE WOULD SAY 4981 03:13:55,880 --> 03:13:58,680 NO, THAT THERE IS AN INFECTION 4982 03:13:58,680 --> 03:14:00,000 ENDOTYPE AND EVEN WITHIN THE 4983 03:14:00,000 --> 03:14:06,640 INFECTION IN IN IN-- -- INDOE 4984 03:14:06,640 --> 03:14:07,800 TYPE WE HAVE TO THINK ABOUT THE 4985 03:14:07,800 --> 03:14:10,240 ARSENAL USED. WILL INTERVENTIONS 4986 03:14:10,240 --> 03:14:12,480 TARGETING ACUTE OUTCOMES IMPROVE 4987 03:14:12,480 --> 03:14:13,960 COG I THINKTIVE OUTCOMES IN 4988 03:14:13,960 --> 03:14:15,160 SURVIVORS. SO BASED UPON WHAT 4989 03:14:15,160 --> 03:14:17,240 WE DISCUSS CYTOTOXIC TAU 4990 03:14:17,240 --> 03:14:21,280 VARIANTS CONTRIBUTE TO END ORGAN 4991 03:14:21,280 --> 03:14:22,480 INJURY DURING CRITICAL ILLNESS 4992 03:14:22,480 --> 03:14:24,040 THEY INDUCE LONG TERM INJURY. 4993 03:14:24,040 --> 03:14:27,000 THEY ARE SELF-REPLICATING AND 4994 03:14:27,000 --> 03:14:28,120 TRANSMISSIBLE AND WE THINK THERE 4995 03:14:28,120 --> 03:14:30,000 IS WINDOW TO TARGET THE 4996 03:14:30,000 --> 03:14:31,720 CYTOTOXIC TAU VARIANTS BY 4997 03:14:31,720 --> 03:14:32,400 MEDICAL THERAPY DURING AND 4998 03:14:32,400 --> 03:14:33,320 PERHAPS THE AFTER MATH OF 4999 03:14:33,320 --> 03:14:36,360 INFECTION. SO WE THINK THE 5000 03:14:36,360 --> 03:14:38,240 ANSWER HERE IS YES. SO WE USE 5001 03:14:38,240 --> 03:14:42,400 THIS THIS REALLY COMMONLY COMMON 5002 03:14:42,400 --> 03:14:44,400 PHOTO TO ILLUSTRATE WE LEARNED A 5003 03:14:44,400 --> 03:14:46,360 LOT BUT THERE IS A LOT HIDDEN 5004 03:14:46,360 --> 03:14:48,320 BELOW WHAT WE ARE UNDERSTANDING. 5005 03:14:48,320 --> 03:14:51,000 SO THINGS GOING FORWARD WE NEED 5006 03:14:51,000 --> 03:14:54,920 TO UNDERSTAND WHICH AND HOW ARE 5007 03:14:54,920 --> 03:14:56,600 THEY DOING IT AND WHEN IS IT 5008 03:14:56,600 --> 03:14:58,200 TRUE AN MORE SPECIFICALLY WHEN 5009 03:14:58,200 --> 03:14:59,760 IT IS NOT TRUE. SOME ONGOING 5010 03:14:59,760 --> 03:15:00,880 EFFORTS OUR GROUP AND THE WAGNER 5011 03:15:00,880 --> 03:15:01,760 GROUP ARE TRYING TO UNDERSTAND 5012 03:15:01,760 --> 03:15:04,360 THIS. WE CHOSE CELLS IN ADDITION 5013 03:15:04,360 --> 03:15:06,320 TO THE ENDOTHELIUM ARE 5014 03:15:06,320 --> 03:15:08,600 CONTRIBUTING TO THIS PHENOMENON, 5015 03:15:08,600 --> 03:15:09,640 AND IMPORTANTLY WHAT IS THE 5016 03:15:09,640 --> 03:15:11,000 STRUCTURAL BASIS OF TAU 5017 03:15:11,000 --> 03:15:12,200 VARIANTS, COULD THIS BE 5018 03:15:12,200 --> 03:15:14,840 SOMETHING WE NEED TO KNOW WHAT 5019 03:15:14,840 --> 03:15:17,000 THE BASIS IS AND WHETHER OR NOT 5020 03:15:17,000 --> 03:15:18,920 THERE'S TROPISM TO VARIANTS 5021 03:15:18,920 --> 03:15:20,520 BRAIN REGIONS DRIVEN BY 5022 03:15:20,520 --> 03:15:23,120 STRUCTURAL BASIS OF THE TAU 5023 03:15:23,120 --> 03:15:25,040 VARIANTS. TO AN EARLIER POINT IN 5024 03:15:25,040 --> 03:15:28,040 THIS SYMPOSIUM, I THINK THIS 5025 03:15:28,040 --> 03:15:29,800 MIGHT BE A SENSITIVE BIOMARKER 5026 03:15:29,800 --> 03:15:31,520 OF INFECTION END ORGAN 5027 03:15:31,520 --> 03:15:33,960 DYSFUNCTION. WE NEED TO 5028 03:15:33,960 --> 03:15:35,200 UNDERSTAND THE BIODISTRIBUTION 5029 03:15:35,200 --> 03:15:37,400 AND HALF LIFE. THIS IS 5030 03:15:37,400 --> 03:15:39,600 ESPECIALLY IMPORTANT DO WE 5031 03:15:39,600 --> 03:15:41,760 DEVELOP IMMUNE RESPONSE AND 5032 03:15:41,760 --> 03:15:43,160 ANTIBODY MEDIATED RESPONSE 5033 03:15:43,160 --> 03:15:45,800 AGAINST CYTOTOXIC VARIANTS OR 5034 03:15:45,800 --> 03:15:49,400 CAN WE USE IMMUNOTHERAPY TO 5035 03:15:49,400 --> 03:15:51,960 LIMIT DISTRIBUTION OF THESE 5036 03:15:51,960 --> 03:15:52,400 CYTOTOXIC VARIANTS. 5037 03:15:52,400 --> 03:15:59,280 >> YOU HIT YOUR TIME. THE OTHER 5038 03:15:59,280 --> 03:16:01,080 ISSUE HOW TO GET INTO CSF. WE 5039 03:16:01,080 --> 03:16:03,160 DON'T KNOW AND NEED TO AND ONCE 5040 03:16:03,160 --> 03:16:06,720 IN THIS CSF HOW TO DISRUPT 5041 03:16:06,720 --> 03:16:07,520 HIPPOCAMPAL INFORMATION 5042 03:16:07,520 --> 03:16:10,160 TRANSFER. THEN FINALLY CAN WE 5043 03:16:10,160 --> 03:16:12,960 DEVELOP MEDICAL THERAPY TO 5044 03:16:12,960 --> 03:16:15,800 REDUCE THIS. SO AS A PATHWAY 5045 03:16:15,800 --> 03:16:16,840 FORE, I WANT TO MAKE A POINT 5046 03:16:16,840 --> 03:16:18,160 THAT I THINK IT IS REALLY 5047 03:16:18,160 --> 03:16:19,880 IMPORTANT WE IDENTIFY THE 5048 03:16:19,880 --> 03:16:22,880 VIRULENCE ARSENAL OF ORGANISMS, 5049 03:16:22,880 --> 03:16:25,200 THAT MAY PRODUCE CYTOTOXIC TAU 5050 03:16:25,200 --> 03:16:27,280 AND ELICIT END ORGAN DYSFUNCTION 5051 03:16:27,280 --> 03:16:28,960 AND EVALUATE EFFICACY FOR 5052 03:16:28,960 --> 03:16:32,200 ANTI-TAU THERAPY. WITH THAT 5053 03:16:32,200 --> 03:16:33,480 I'LL END AND TAKE QUESTIONS. 5054 03:16:33,480 --> 03:16:34,480 THANK YOU. 5055 03:16:34,480 --> 03:16:35,720 >> THANK YOU. FOR YOUR TIME 5056 03:16:35,720 --> 03:16:37,080 TROY. WE ARE GOING TO SAVE THE 5057 03:16:37,080 --> 03:16:38,120 QUESTIONS FOR THE DISCUSSION 5058 03:16:38,120 --> 03:16:39,560 AFTERWARDS. I'M GOING TO HAND 5059 03:16:39,560 --> 03:16:41,520 THE REIGNS TO BEN. TO INTRODUCE 5060 03:16:41,520 --> 03:16:43,360 THE NEXT SPEAKER. PLENTY OF 5061 03:16:43,360 --> 03:16:44,920 TIMES TA END TO CONTINUE TO 5062 03:16:44,920 --> 03:16:46,320 DISCUSS. THANK YOU AGAIN. 5063 03:16:46,320 --> 03:16:49,040 >> THANK YOU, TROY. IT IS MY 5064 03:16:49,040 --> 03:16:53,280 PLEASURE TO INTRODUCE DR. SHOURI 5065 03:16:53,280 --> 03:16:55,600 LAHIRI FOR THE NEXT TALK. DR. 5066 03:16:55,600 --> 03:16:58,080 LAHIRI IS PHYSICIAN SCIENTIST 5067 03:16:58,080 --> 03:16:59,560 AND ASSOCIATE PROFESSOR CEDAR 5068 03:16:59,560 --> 03:17:01,160 SINAI MEDICAL CENTER, DIRECTOR 5069 03:17:01,160 --> 03:17:03,040 OF THE NEUROSCIENCE CRITICAL 5070 03:17:03,040 --> 03:17:04,800 CARE UNIT AS WELL AS CRITICAL 5071 03:17:04,800 --> 03:17:07,080 CARE RESEARCH. HIS LABORATORY TO 5072 03:17:07,080 --> 03:17:09,280 US CONSIST ON MECHANISTIC 5073 03:17:09,280 --> 03:17:11,960 UNDERPINNINGS OF ACUTE BRAIN 5074 03:17:11,960 --> 03:17:15,120 DYSFUNCTION OR DE DELIRIUM 5075 03:17:15,120 --> 03:17:16,640 INCLUDING DISCOVERY OF 5076 03:17:16,640 --> 03:17:19,240 BIOMARKERS OR OTHER MARKERS FOR 5077 03:17:19,240 --> 03:17:21,160 CLEARING AN ACUTE BRAIN 5078 03:17:21,160 --> 03:17:23,960 DYSFUNCTION AND ALSO MECHANISMS 5079 03:17:23,960 --> 03:17:26,360 THAT LEAD TO BRAIN DYSFUNCTION. 5080 03:17:26,360 --> 03:17:30,000 DR. LAHIRI, THANK YOU FOR JOIN 5081 03:17:30,000 --> 03:17:37,600 US. 5082 03:17:37,600 --> 03:17:39,480 >> PLEASURE TO BE HERE. SHOUT 5083 03:17:39,480 --> 03:17:41,160 OUT TO DR. HAROLD FROM THE FIRST 5084 03:17:41,160 --> 03:17:43,240 SESSION AND THANK HER FOR THAT 5085 03:17:43,240 --> 03:17:45,920 NARRATIVE AND ALSO MOTIVATION 5086 03:17:45,920 --> 03:17:48,120 HEART WRENCHING BUT MOTIVATING 5087 03:17:48,120 --> 03:17:54,440 STORY OF HER STRUGGLES. 5088 03:17:54,440 --> 03:17:58,240 ROLE OF EL 6 IN INDUCED 5089 03:17:58,240 --> 03:18:01,600 DELIRIUM, DISCLOSURES. AS HAS 5090 03:18:01,600 --> 03:18:05,320 BEEN IT RATED, DELIRIUM IS ACUTE 5091 03:18:05,320 --> 03:18:06,520 CONFUSIONAL STATE CHARACTERIZED 5092 03:18:06,520 --> 03:18:07,440 BY INTENTIONAL PROBLEMS 5093 03:18:07,440 --> 03:18:08,840 EXECUTIVE DISFUNCTION, SHORT 5094 03:18:08,840 --> 03:18:12,480 TERM MEMORY IMPAIRMENT. IT MAYBE 5095 03:18:12,480 --> 03:18:14,120 INVARIABLE FEATURE OF ARDS 5096 03:18:14,120 --> 03:18:16,960 OCCURRING IN BETWEEN 70 TO 100% 5097 03:18:16,960 --> 03:18:19,440 PATIENTS. IT IS NOT JUST A 5098 03:18:19,440 --> 03:18:23,600 MARKER OF BAD BRAIN SUBSTRATE, 5099 03:18:23,600 --> 03:18:25,800 UNMASKING OF BAD BRAIN SUBSTRATE 5100 03:18:25,800 --> 03:18:28,760 BUT SOMETHING THAT ACT SET RATED 5101 03:18:28,760 --> 03:18:30,480 DEMENTIA AND LONG TERM 5102 03:18:30,480 --> 03:18:32,400 NEURODEGENERATION. THAT IS 5103 03:18:32,400 --> 03:18:35,240 CLEARING NOW INSUSCEPTIBLE 5104 03:18:35,240 --> 03:18:37,320 PATIENT POPULATION THE RISK OF 5105 03:18:37,320 --> 03:18:39,280 DEMENTIA DOUBLES WITH EXPOSURE 5106 03:18:39,280 --> 03:18:43,440 TO DELIRIUM VERSUS NOT. SO MAYBE 5107 03:18:43,440 --> 03:18:45,040 ONE FEW MUCH NEEDED 5108 03:18:45,040 --> 03:18:48,520 OPPORTUNITIES TO MODIFY LONG 5109 03:18:48,520 --> 03:18:50,160 TERM COGNITIVE IMPAIRMENT AND 5110 03:18:50,160 --> 03:18:51,200 ADDRESS NEW PANDEMIC WE ARE 5111 03:18:51,200 --> 03:18:53,640 GETTING INTO OF DEMENTIA 5112 03:18:53,640 --> 03:18:54,680 ALZHEIMER'S DISEASE AND RELATED 5113 03:18:54,680 --> 03:18:58,720 DEMENTIAS. CLEARLY THERE IS A 5114 03:18:58,720 --> 03:19:02,000 SIGNIFICANT NEED TO UNDERSTAND 5115 03:19:02,000 --> 03:19:03,680 UNDERLYING BIOLOGICAL MECHANISMS 5116 03:19:03,680 --> 03:19:06,000 IT IS HETEROGENOUS DISEASE BUT 5117 03:19:06,000 --> 03:19:07,040 SPECIFIC SPECIFICALLY PHENOTYPE 5118 03:19:07,040 --> 03:19:08,760 POPULATIONS IT GREATLY HELP OUR 5119 03:19:08,760 --> 03:19:11,600 CAUSE TO ADDRESS BIOLOGICAL 5120 03:19:11,600 --> 03:19:13,760 MECHANISMS THAT REMAIN UNKNOWN. 5121 03:19:13,760 --> 03:19:14,920 ONE OF THE REASONS IT IS 5122 03:19:14,920 --> 03:19:16,520 REMAINED UNKNOWN IS BECAUSE WE 5123 03:19:16,520 --> 03:19:19,800 HAVE LACKED OF COURSE CLINICAL 5124 03:19:19,800 --> 03:19:22,480 LITERATURE IS IT RATED MULTIPLE 5125 03:19:22,480 --> 03:19:24,320 TIMES IN THE PRIOR SESSION BUT 5126 03:19:24,320 --> 03:19:27,680 WHAT WE DON'T HAVE IS MECHANISMS 5127 03:19:27,680 --> 03:19:30,520 FROM PRE-CLINICAL MODEL OR 5128 03:19:30,520 --> 03:19:33,160 ANIMAL MODELS. BECAUSE DELIRIUM 5129 03:19:33,160 --> 03:19:34,800 IS NOT STUDIED THROUGH BASIC 5130 03:19:34,800 --> 03:19:38,480 LEVEL OF ANALYSIS SO IN ORDER TO 5131 03:19:38,480 --> 03:19:43,560 GET TO SOME OF THAT WHAT WE 5132 03:19:43,560 --> 03:19:44,880 FOCUS ON AND SHARE THAT DATA 5133 03:19:44,880 --> 03:19:46,040 WITH YOU OR THAT APPROACH WITH 5134 03:19:46,040 --> 03:19:51,760 YOU. INTERLEUKIN 6 POPS UP 5135 03:19:51,760 --> 03:19:55,520 EVERYWHERE, THERE IS A REASON 5136 03:19:55,520 --> 03:19:58,520 STUDY ON POST-OPERATIVE DELIRIUM 5137 03:19:58,520 --> 03:20:01,000 AND ROAM OF IL 6. THIS IS 5138 03:20:01,000 --> 03:20:02,320 UNPUBLISHED HUMAN DATA FROM 5139 03:20:02,320 --> 03:20:07,120 VANDERBILT COHORT PROVIDED TO ME 5140 03:20:07,120 --> 03:20:10,960 BY DR. WEST HEELEY. THESE ARE 5141 03:20:10,960 --> 03:20:13,840 LUNG RELATED REASONS. INCLUDE 5142 03:20:13,840 --> 03:20:15,240 PATIENTS WITH ARDS AND PATIENTS 5143 03:20:15,240 --> 03:20:20,480 WITH COPD OR INTUBATED FOR 5144 03:20:20,480 --> 03:20:21,280 AIRWAY SUPPRESSION. ET CETERA. 5145 03:20:21,280 --> 03:20:23,040 THIS IS UNADJUSTED FOR AGE SEX 5146 03:20:23,040 --> 03:20:28,080 AND OTHER FACTORS BUT IT IS 5147 03:20:28,080 --> 03:20:29,400 STRIKING THAT IN SUCH A 5148 03:20:29,400 --> 03:20:30,080 HETEROGENOUS PATIENT POPULATION 5149 03:20:30,080 --> 03:20:35,760 IN ICU, THAT IL 6 EXPLAINED 6% 5150 03:20:35,760 --> 03:20:41,000 VARIATION OF DELIRIUM DURATION. 5151 03:20:41,000 --> 03:20:43,840 SO THAT IS STARTING POINT. 5152 03:20:43,840 --> 03:20:44,600 CORRELATION DOESN'T PROVE 5153 03:20:44,600 --> 03:20:47,800 CAUSATION SO WE NEEDED TO 5154 03:20:47,800 --> 03:20:49,880 ADDRESS THIS WITH IN ISOLATED 5155 03:20:49,880 --> 03:20:52,400 MANNER ISOLATING VARIABLES, SO 5156 03:20:52,400 --> 03:20:57,080 WE DEVELOPED A MODEL FOR 5157 03:20:57,080 --> 03:20:58,760 VENTILATOR INDUCED INJURY TO 5158 03:20:58,760 --> 03:21:01,120 SIMULATE ARDS. SO TO DO THAT, 5159 03:21:01,120 --> 03:21:06,520 THE FIRST ASPECT OF THAT IS TO 5160 03:21:06,520 --> 03:21:07,760 DEVELOP BEHAVIOR I DON'T RECALL 5161 03:21:07,760 --> 03:21:09,280 PHENOTYPES THAT REPLICATE 5162 03:21:09,280 --> 03:21:10,920 DELIRIUM. SO WE LOOK AT MULTIPLE 5163 03:21:10,920 --> 03:21:13,000 DIFFERENT ASSAYS ONE OF THEM IS 5164 03:21:13,000 --> 03:21:14,560 THE OPEN FIELD ASSAY, 5165 03:21:14,560 --> 03:21:15,600 QUANTIFYING AMOUNT OF TIME THE 5166 03:21:15,600 --> 03:21:16,920 ANIMAL SPENDS IN THE PERIPHERY 5167 03:21:16,920 --> 03:21:18,800 OF THE MAZE COMPARED TO CENTER. 5168 03:21:18,800 --> 03:21:21,280 AS MARKER OF ANXIETY EXECUTIVE 5169 03:21:21,280 --> 03:21:23,800 DYSFUNCTION, WE ALSO LOOK AT 5170 03:21:23,800 --> 03:21:25,560 ELEVATED PLUS MAZE WHICH IS A 5171 03:21:25,560 --> 03:21:26,760 CROSS SHAPE MAZE WITH AN OPEN 5172 03:21:26,760 --> 03:21:29,520 ARM AND CLOSED ARM AND ANXIOUS 5173 03:21:29,520 --> 03:21:32,040 ANIMALS AVOID THE OPEN ARM AND 5174 03:21:32,040 --> 03:21:37,000 PREFER STAY IN THE CLOSED ARM. 5175 03:21:37,000 --> 03:21:38,520 ALSO ABLE TO CAPTURE THE 5176 03:21:38,520 --> 03:21:39,520 FLUCTUATING ACTIVITY OF THE 5177 03:21:39,520 --> 03:21:41,560 ANIMAL'S COURSE OF ACTIVITY VIA 5178 03:21:41,560 --> 03:21:42,720 CALCULATION OF COEFFICIENT OF 5179 03:21:42,720 --> 03:21:44,440 VARIATION. THAT'S ALL PART OF 5180 03:21:44,440 --> 03:21:51,800 THE OPEN FIELD ASSESSMENT. WE 5181 03:21:51,800 --> 03:21:53,120 EVALUATE ATTENTION AND SHORT 5182 03:21:53,120 --> 03:21:54,600 TERM MEMORY FOR RECOGNITION, 5183 03:21:54,600 --> 03:21:56,280 PRESENCING A NOVEL OBJECT AND 5184 03:21:56,280 --> 03:22:00,000 FAMILIAR OBJECT TO ANIMAL, AND 5185 03:22:00,000 --> 03:22:01,760 THEN ASSAY TIME SPENT WITH EACH 5186 03:22:01,760 --> 03:22:03,080 OBJECT AND IF THEY SPEND MORE 5187 03:22:03,080 --> 03:22:04,560 TIME WITH NOVEL OBJECT THAT'S 5188 03:22:04,560 --> 03:22:05,920 NORMAL, THEY GO BACK TO THE 5189 03:22:05,920 --> 03:22:09,880 FAMILIAR OBJECT AND THAT'S 5190 03:22:09,880 --> 03:22:11,360 ABNORMAL RESPONSE AND INDICATING 5191 03:22:11,360 --> 03:22:13,360 LACK OF SHORT TERM MEMORY OR 5192 03:22:13,360 --> 03:22:15,640 ATTENTION. THE Y MAZE 5193 03:22:15,640 --> 03:22:17,560 SPONTANEOUS ALTERATION IS 5194 03:22:17,560 --> 03:22:20,240 ANOTHER ASSAY WHICH LEVERAGES 5195 03:22:20,240 --> 03:22:22,720 THE IDEA NORMAL ANIMAL 5196 03:22:22,720 --> 03:22:25,120 ALTERNATES BETWEEN ARM ARMS OF 5197 03:22:25,120 --> 03:22:26,680 YMA AND THE THE INJURED ANIMAL 5198 03:22:26,680 --> 03:22:28,880 BACK TO SAME ARM YMA INDICATION 5199 03:22:28,880 --> 03:22:30,160 OF ATTENTION AND SHORT TERM 5200 03:22:30,160 --> 03:22:32,160 MEMORY. SO WE USE A WIDE RANGE 5201 03:22:32,160 --> 03:22:34,960 OF BEHAVIORAL ASSAYS AND TEST 5202 03:22:34,960 --> 03:22:41,960 PRE-INJURY AND POST INJURY READ 5203 03:22:41,960 --> 03:22:45,120 OUTS. IN THE VENTILATOR INDUCED 5204 03:22:45,120 --> 03:22:47,120 LUNG INJURE SRI MODEL, WE USE 5205 03:22:47,120 --> 03:22:48,600 DIFFERENT APPROACHES TO INDUCE 5206 03:22:48,600 --> 03:22:52,400 LUNG INJURY. ONE WE USED MOST IS 5207 03:22:52,400 --> 03:22:56,600 THE 35CC KILOGRAM HYDRIDER 5208 03:22:56,600 --> 03:22:57,960 VOLUME, THIS IS ALSO USED IN ONE 5209 03:22:57,960 --> 03:23:00,040 OF THE EARLIER STUDIES DR. 5210 03:23:00,040 --> 03:23:03,440 GERARD MENTIONED THAT LED TO THE 5211 03:23:03,440 --> 03:23:04,200 RECOMMENDATIONS OF LARGE 5212 03:23:04,200 --> 03:23:07,640 CLINICAL TRIAL ON USING LOW 5213 03:23:07,640 --> 03:23:08,800 TITER VOLUME VENTILATION THAT 5214 03:23:08,800 --> 03:23:10,480 RESULTED IN CHANGE OF OUTCOMES. 5215 03:23:10,480 --> 03:23:12,480 WE QUANTITY QUANTIFIED PRESENCE 5216 03:23:12,480 --> 03:23:14,480 OF VENTILATOR INJURY BY LOOKING 5217 03:23:14,480 --> 03:23:17,240 AT LUNG INFLAMMATION, ALBUMIN, 5218 03:23:17,240 --> 03:23:20,760 STAINING THINNING OF ALVEOLAR 5219 03:23:20,760 --> 03:23:24,080 WALLS ET CETERA. OUR BRAIN READ 5220 03:23:24,080 --> 03:23:26,520 OUT IS THAT OF CASPASE 3, 5221 03:23:26,520 --> 03:23:30,960 SOMETHING WE FOUND TO BE 5222 03:23:30,960 --> 03:23:32,520 PREDICTIVE OF BEHAVIORAL 5223 03:23:32,520 --> 03:23:33,760 IMPAIRMENT SO THIS CLEAVE 5224 03:23:33,760 --> 03:23:35,760 CASPASE 3 EXPRESS IN FRONTAL 5225 03:23:35,760 --> 03:23:37,040 CORTEX HIPPOCAMPUS WHICH ARE THE 5226 03:23:37,040 --> 03:23:39,040 AREAS OF THE BRAIN THAT SYMPTOMS 5227 03:23:39,040 --> 03:23:42,960 OF DELIRIUM LOCALIZE TO APPEAR 5228 03:23:42,960 --> 03:23:47,120 TO PREDICT BEHAVIORAL 5229 03:23:47,120 --> 03:23:49,480 PERFORMANCE OF INDIVIDUAL ANIMAL 5230 03:23:49,480 --> 03:23:54,760 LEVEL BUT INCLUDE 10 CC 5231 03:23:54,760 --> 03:23:59,600 MECHANICAL VENTILATION GROUP TO 5232 03:23:59,600 --> 03:24:01,760 DISENTANGLE VENTILATOR EFFECTS. 5233 03:24:01,760 --> 03:24:02,960 SO WHAT WE SEE IN GREEN IS 5234 03:24:02,960 --> 03:24:06,320 EXPRESS OF CC 3 FRONTAL CORTEX 5235 03:24:06,320 --> 03:24:07,400 HIPPOCAMPUS, SIGNIFICANTLY MORE 5236 03:24:07,400 --> 03:24:14,400 SO IN THE LUNG INJURY GROUP THE 5237 03:24:14,400 --> 03:24:16,120 VILLE -- COMPARED TO THE 5238 03:24:16,120 --> 03:24:18,200 BREATHING GROUP. AT INDIVIDUAL 5239 03:24:18,200 --> 03:24:20,080 ANIMAL LEVEL AMOUNT OF CC 3 5240 03:24:20,080 --> 03:24:27,280 EXPRESSION APPEARS TO PREDICT 5241 03:24:27,280 --> 03:24:29,360 PERFORMANCE OF BEHAVIORAL 5242 03:24:29,360 --> 03:24:30,720 TESTING MORE THEY SPENDS HIGHER 5243 03:24:30,720 --> 03:24:32,840 RIFF PRIA, THE HIGHER THE CC 3 5244 03:24:32,840 --> 03:24:34,520 LESS TIME OPEN ARM OF ELEVATED 5245 03:24:34,520 --> 03:24:38,960 PLUS MAZE AND HIGHER THE CC 3 5246 03:24:38,960 --> 03:24:40,640 LESS SPONTANEOUS ALTERNATIONS 5247 03:24:40,640 --> 03:24:41,960 THEY PERFORM. SO IT IS A 5248 03:24:41,960 --> 03:24:49,160 STRUCTURAL MARKER OF DELIRIUM. 5249 03:24:49,160 --> 03:24:54,520 SO IN ORDER TO EVALUATE EFFECT 5250 03:24:54,520 --> 03:24:57,240 OF PERIPHERAL I L 6 ANING THE 5251 03:24:57,240 --> 03:24:58,840 NICHE WE DID AN EXPERIMENT 5252 03:24:58,840 --> 03:25:02,360 ADMINISTERING TWO TYPES OF IL 6 5253 03:25:02,360 --> 03:25:05,080 INHIBITORS IN THE PERIPHERY THAT 5254 03:25:05,080 --> 03:25:08,680 WAS IL 6 ANTIBODY AND RECEPTOR 5255 03:25:08,680 --> 03:25:11,480 AND WE ADMINISTERED THIS AS A 5256 03:25:11,480 --> 03:25:12,120 PREVENTIVE TREATMENT PRIOR TO 5257 03:25:12,120 --> 03:25:19,640 THE ONSET OF VENTILATION AND 5258 03:25:19,640 --> 03:25:25,040 LUNG INJURY. WE FOUND CC 3 FULLY 5259 03:25:25,040 --> 03:25:26,280 REVERSED ABOUT IL 6 TREATED 5260 03:25:26,280 --> 03:25:28,960 GROUP FRONTAL CORTEX HIPPOCAMPUS 5261 03:25:28,960 --> 03:25:34,440 WITH NO EFFECT OF LUNG 5262 03:25:34,440 --> 03:25:36,920 INFLAMMATION ITSELF THIS 5263 03:25:36,920 --> 03:25:39,040 CORRESPONDED TO IMPROVEMENTS IN 5264 03:25:39,040 --> 03:25:40,280 DELIRIUM LIKE BEHAVIOR ACROSS 5265 03:25:40,280 --> 03:25:44,840 MULTIPLE ASSAYS IN OPEN FIELD, Y 5266 03:25:44,840 --> 03:25:46,840 MAZE. WE HAD TO OPTIMIZE TIME, 5267 03:25:46,840 --> 03:25:48,960 THIS IS A TRICKY MODEL BECAUSE 5268 03:25:48,960 --> 03:25:51,720 YOU HAVE TO DISENTANGLE AFFECT 5269 03:25:51,720 --> 03:25:55,680 OF LIMITED MOBILITY FROM LUNG 5270 03:25:55,680 --> 03:25:57,240 INJURY LUNG INFLAMMATION AND THE 5271 03:25:57,240 --> 03:25:58,960 FACT IF YOU LET THEM RECOVER 5272 03:25:58,960 --> 03:26:01,640 LONGER PERIODS OF TIME THEIR 5273 03:26:01,640 --> 03:26:04,880 BRAIN FUNCTION RECOVER BUT THIS 5274 03:26:04,880 --> 03:26:10,360 IS ACUTE BILI MODEL. SO THE 5275 03:26:10,360 --> 03:26:11,320 MOUSE DATA INDICATES PERIPHERAL 5276 03:26:11,320 --> 03:26:13,280 PLASMA IL 6 PREDICTS THE 5277 03:26:13,280 --> 03:26:14,960 STRUCTURAL DELIRIUM LIKE 5278 03:26:14,960 --> 03:26:17,040 PHENOTYPE CC 3 AND CLINICAL DATA 5279 03:26:17,040 --> 03:26:18,880 SHOWED EARLIER SEEMS TO SUGGEST 5280 03:26:18,880 --> 03:26:22,000 THAT IL 6 IN THE PERIPHERY 5281 03:26:22,000 --> 03:26:25,800 PREDICTS DELIRIUM SEVERITY. SO 5282 03:26:25,800 --> 03:26:27,920 WHICH HYPOTHESIZE IL 6 5283 03:26:27,920 --> 03:26:29,040 TRANSITIONNALLING PATHWAY 5284 03:26:29,040 --> 03:26:30,680 UNDERLYING THE DELIRIUM LIKE 5285 03:26:30,680 --> 03:26:34,320 PHENOTYPE WE SEE IN THIS PATHWAY 5286 03:26:34,320 --> 03:26:38,240 YOU HAVE RELEASE OF I IL 6 5287 03:26:38,240 --> 03:26:40,080 INDUCED FROM LUNG INFLAMMATION 5288 03:26:40,080 --> 03:26:42,520 BUT ALSO INFECTIOUS MODELS OF 5289 03:26:42,520 --> 03:26:44,720 INTRATRACHEAL LPS AND URINARY 5290 03:26:44,720 --> 03:26:47,080 TRACT INFECTION MODEL. AND FOUND 5291 03:26:47,080 --> 03:26:51,480 THAT WHEN YOU RELEASE IL 6 IT 5292 03:26:51,480 --> 03:26:53,800 BINDS TO SOOLABLE IL 6 RECEPTOR 5293 03:26:53,800 --> 03:26:55,600 IN THE BLOOM PERIPHERY AND THEN 5294 03:26:55,600 --> 03:26:57,440 IT -- BLOOD PERIPHERY AND GAIN 5295 03:26:57,440 --> 03:26:59,600 ENTRY TO NEURONS GP 130 5296 03:26:59,600 --> 03:27:01,840 TRANSMEMBRANE PROTEIN WITHOUT 5297 03:27:01,840 --> 03:27:02,480 NEEDING TO BIND CLASSICAL 5298 03:27:02,480 --> 03:27:03,960 MEMBRANE RECEPTORS WHICH NEURONS 5299 03:27:03,960 --> 03:27:05,680 WOULD LACK ANYWAY. SO THIS 5300 03:27:05,680 --> 03:27:07,800 PATHWAY IS IN SOME WAYS 5301 03:27:07,800 --> 03:27:09,200 INDEPENDENT OF THE MICROGLIA 5302 03:27:09,200 --> 03:27:12,920 STORY BUT CERTAINLY I ALSO AGREE 5303 03:27:12,920 --> 03:27:15,840 WITH PRIOR SPEAKERS THAT THERE 5304 03:27:15,840 --> 03:27:18,000 IS SIGNIFICANT RELEVANCE OF THE 5305 03:27:18,000 --> 03:27:19,600 MICROGLIA PATHWAY AS INFECTION 5306 03:27:19,600 --> 03:27:20,600 PARTICULARLY AS INFECTION 5307 03:27:20,600 --> 03:27:29,600 EVOLVES OVER TIME. TO TEST THIS 5308 03:27:29,600 --> 03:27:32,200 THEORY IN PATIENT, I AGAIN 5309 03:27:32,200 --> 03:27:35,200 DISCUSSED THE FINDINGS WITH MY 5310 03:27:35,200 --> 03:27:39,200 FRIEND MENTOR AND COLLEAGUE WE S 5311 03:27:39,200 --> 03:27:43,080 ELI VANDERBILT. WE DECIDED TO 5312 03:27:43,080 --> 03:27:46,720 LOOK AT THE DATA IN HIS CLINICAL 5313 03:27:46,720 --> 03:27:48,760 PATIENT COHORT. THIS IS PRE-AND 5314 03:27:48,760 --> 03:27:54,760 POST ADVENT OF TOZILIZMAB 5315 03:27:54,760 --> 03:27:55,560 INHIBITOR FOR COVID TREATMENT. 5316 03:27:55,560 --> 03:27:57,960 THE THEORY WAS AFTER THE ONSET 5317 03:27:57,960 --> 03:28:00,840 OR AFTER THE ADVENT OF TOCI 5318 03:28:00,840 --> 03:28:03,120 THERE IS SIGNIFICANTLY LESS 5319 03:28:03,120 --> 03:28:06,800 DELIRIUM IN MATCHED PATIENTS. SO 5320 03:28:06,800 --> 03:28:08,080 INCLUDED PATIENTS WITH AGE 5321 03:28:08,080 --> 03:28:09,400 ADULTS DIAGNOSE WITH COVID 5322 03:28:09,400 --> 03:28:11,800 INFECTION ADMITTED TO THE NICU 5323 03:28:11,800 --> 03:28:14,480 IN VANDERBILT OR COVID ICU. THE 5324 03:28:14,480 --> 03:28:18,240 CONTROL GROUP RECEIVED STEROIDS, 5325 03:28:18,240 --> 03:28:21,520 TOCI GROUP RECEIVED STEROIDS AND 5326 03:28:21,520 --> 03:28:25,600 TOCI AND EXCLUDED PREGNANT WOMEN 5327 03:28:25,600 --> 03:28:27,160 AND PRISES NEARS IN THE STUDY. 5328 03:28:27,160 --> 03:28:29,960 THE LIKELY OUTCOME IS 21 DAY, 5329 03:28:29,960 --> 03:28:35,120 PRETTY STANDARD WELL ESTABLISHED 5330 03:28:35,120 --> 03:28:38,400 PRIMARY OUTCOME LOOKED MULTIPLE 5331 03:28:38,400 --> 03:28:39,240 STUDIES VANDERBILT GROUP AND 5332 03:28:39,240 --> 03:28:42,880 SECOND ONES WE KNOW ARE AFFECTED 5333 03:28:42,880 --> 03:28:45,880 POSITIVELY BY TOCI TREATMENT, 90 5334 03:28:45,880 --> 03:28:49,160 DAY MORTALITY, HOSPITAL LENGTH 5335 03:28:49,160 --> 03:28:50,960 OF THE STAY NUMBER OF DAYS 5336 03:28:50,960 --> 03:28:52,720 MECHANICAL VENTILATION. THIS IS 5337 03:28:52,720 --> 03:28:53,560 UNPUBLISHED DATA IN GOING 5338 03:28:53,560 --> 03:28:56,120 THROUGH THE PROCESS OF 5339 03:28:56,120 --> 03:28:57,840 SUBMITTING NOW BUT SO THERE IS 5340 03:28:57,840 --> 03:29:02,400 SOME DIFFERENCES, SOME 5341 03:29:02,400 --> 03:29:05,240 DIFFERENCES IN AGE, SEX, 5342 03:29:05,240 --> 03:29:08,800 CHARLESTON INDEX SEVERITY INDEX 5343 03:29:08,800 --> 03:29:12,720 AND NONE IN USE OF OPIATES OR 5344 03:29:12,720 --> 03:29:14,360 MEDAZLAM, KNOWN CONFOUNDERS IN 5345 03:29:14,360 --> 03:29:18,000 DELIRIUM. AND THOSE ARE THE 5346 03:29:18,000 --> 03:29:19,320 OUTCOME DAYS IN THIS UNIVARIANT 5347 03:29:19,320 --> 03:29:21,480 ANALYSIS. THERE'S THREE DAYS OF 5348 03:29:21,480 --> 03:29:22,800 DELIRIUM FREEDOM IN CONTROL 5349 03:29:22,800 --> 03:29:24,920 GROUP, SEVIN IN THE THE,OCI 5350 03:29:24,920 --> 03:29:26,720 GROUP, THAT WAS SIGNIFICANTLY 5351 03:29:26,720 --> 03:29:27,920 DIFFERENT IN UNIVARIANT 5352 03:29:27,920 --> 03:29:30,480 ANALYSIS. NO DIFFERENT IN IN 5353 03:29:30,480 --> 03:29:33,520 MORTALITY ICU LENGTH OF STAY 5354 03:29:33,520 --> 03:29:34,160 HOSPITAL LENGTH OF STAY. THAT IS 5355 03:29:34,160 --> 03:29:35,560 INTERESTING BECAUSE THOSE ARE WE 5356 03:29:35,560 --> 03:29:38,480 KNOW THAT TOCI POSITIVELY 5357 03:29:38,480 --> 03:29:43,640 AFFECTS OUTCOMES BUT HERE STILL 5358 03:29:43,640 --> 03:29:45,840 EFFECT ON DELIRIUM AND 5359 03:29:45,840 --> 03:29:47,440 MULTI-DURATIONAL ANALYSIS THIS 5360 03:29:47,440 --> 03:29:49,840 HELD TRUE WITH THE TOCI GROUP 5361 03:29:49,840 --> 03:29:51,840 PREDICTING THE TOCI GROUP HAVING 5362 03:29:51,840 --> 03:29:55,280 INCREASE ODDS OF DELIRIUM 5363 03:29:55,280 --> 03:29:57,680 FREEDOM OR IN THE FIRST # 1 DAYS 5364 03:29:57,680 --> 03:30:00,760 WITH P VALUE .007. SO IN 5365 03:30:00,760 --> 03:30:01,680 SUMMARY, THERE WAS NO DIFFERENCE 5366 03:30:01,680 --> 03:30:05,120 IN VENTILATOR LENGTH, VENTILATOR 5367 03:30:05,120 --> 03:30:07,040 DOES RATION, HOSPITAL LENGTH OF 5368 03:30:07,040 --> 03:30:09,440 STAY, ICU LENGTH OF STAY OR 5369 03:30:09,440 --> 03:30:11,680 MORTALITY 90 DAYS BUT 5370 03:30:11,680 --> 03:30:12,920 SIGNIFICANT DIFFERENCE IN 5371 03:30:12,920 --> 03:30:15,600 DELIRIUM COMA FREE DAYS IN THE 5372 03:30:15,600 --> 03:30:17,440 TOCI TREATED GROUP. THE ANTI-IL 5373 03:30:17,440 --> 03:30:19,160 6 TREATED GROUP SO I MANY TAKE 5374 03:30:19,160 --> 03:30:22,240 OF THIS IS, DESPITE BEING 5375 03:30:22,240 --> 03:30:28,760 UNDERPOWERED TO DETECT THE KNOWN 5376 03:30:28,760 --> 03:30:30,080 DESPITE UNDERPOWERED TO DETECT 5377 03:30:30,080 --> 03:30:33,520 THE KNOWN EFFECTS OF TOCI ON 5378 03:30:33,520 --> 03:30:34,560 VENTILATOR DURATION HOSPITAL 5379 03:30:34,560 --> 03:30:36,920 LENGTH OF STAY, ISO LENGTH OF 5380 03:30:36,920 --> 03:30:38,520 STAY MORTALITY, THERE WAS EFFECT 5381 03:30:38,520 --> 03:30:40,600 ON DELIRIUM AND COMA. WHICH 5382 03:30:40,600 --> 03:30:43,520 SUGGESTS THAT PERHAPS THE 5383 03:30:43,520 --> 03:30:44,640 ANTI-IL 6 TREATMENT IS ACTUALLY 5384 03:30:44,640 --> 03:30:48,400 HAS A GREATER TREATMENT EFFECT 5385 03:30:48,400 --> 03:30:50,640 ORNATE LEER YUM THAN OTHER YOU 5386 03:30:50,640 --> 03:30:53,480 OUT COMES KNOWN TO AFFECT BY 5387 03:30:53,480 --> 03:30:57,240 TOCI. SO IN SUMMARY, THE CURRENT 5388 03:30:57,240 --> 03:30:58,880 KNOWLEDGE GAPS IN FUTURE 5389 03:30:58,880 --> 03:30:59,960 RESEARCH IN MY MIND WE HAVE TO 5390 03:30:59,960 --> 03:31:03,720 DO A PROSPECTIVE CLINICAL TRIAL 5391 03:31:03,720 --> 03:31:04,720 INHIBITS IL 6 TRANSITIONNALLING 5392 03:31:04,720 --> 03:31:08,320 BASED ON DATA, WE NEED TO 5393 03:31:08,320 --> 03:31:09,040 DISAGGREGATE DELIRIUM TO 5394 03:31:09,040 --> 03:31:10,440 DISTINCT PATIENT SUB SETS BASED 5395 03:31:10,440 --> 03:31:13,080 ON MOLECULAR CLASSIFIERS IN THIS 5396 03:31:13,080 --> 03:31:14,760 INCLUDES LOOKING AT HYPO ACTIVE 5397 03:31:14,760 --> 03:31:18,880 AND HYPERACTIVE PHENOTYPES, COMA 5398 03:31:18,880 --> 03:31:22,760 IS CERTAINLY FORM OF HYPO ACTIVE 5399 03:31:22,760 --> 03:31:25,360 DELIRIUM, THESE DISTINCT DISEASE 5400 03:31:25,360 --> 03:31:27,440 OR REFLECT CONTINUUM OF 5401 03:31:27,440 --> 03:31:29,160 SEVERITIES. WE HAVE DATA TO 5402 03:31:29,160 --> 03:31:31,760 SUGGEST THAT THE LATTER IS TRUE 5403 03:31:31,760 --> 03:31:33,800 WE NEED TO LOOK AT PERIPHERAL 5404 03:31:33,800 --> 03:31:35,280 HORMONAL AND IMMUNOLOGICAL 5405 03:31:35,280 --> 03:31:36,880 INTERACTIONS IN DELIRIUM. WHAT 5406 03:31:36,880 --> 03:31:41,720 IS THE ROLE OF ESTROGEN IN 5407 03:31:41,720 --> 03:31:43,400 SUPPRESSING PERIPHERAL 5408 03:31:43,400 --> 03:31:44,160 INFLAMMATIONMATION AND 5409 03:31:44,160 --> 03:31:47,680 MITIGATING DELIRIUM. WE HAVE 5410 03:31:47,680 --> 03:31:49,880 OTHER DATA THAT I HAVEN'T SHOW 5411 03:31:49,880 --> 03:31:53,240 THAT SHOWS POST MENOPAUSAL MICE 5412 03:31:53,240 --> 03:31:56,600 REPLEASE OF 17 BETA AS STRAY 5413 03:31:56,600 --> 03:31:58,320 DIAL AMELIORATES DELIRIUM AND 5414 03:31:58,320 --> 03:32:01,880 THAT OCCURS THROUGH PERIPHERAL I 5415 03:32:01,880 --> 03:32:04,040 ALREADY -- IL 6 SUPPRESSION. AS 5416 03:32:04,040 --> 03:32:06,440 MENTIONED BY PRIOR SPEAKERS 5417 03:32:06,440 --> 03:32:08,120 EVALUATE BRAIN IMMUNOLOGICAL SO 5418 03:32:08,120 --> 03:32:10,520 FAR FOCUSED ON SYSTEMIC 5419 03:32:10,520 --> 03:32:11,760 IMMUNOLOGICAL RESPONSE MICROGLIA 5420 03:32:11,760 --> 03:32:13,200 IN PARTICULAR AND MICROGLIAL 5421 03:32:13,200 --> 03:32:15,160 REACTIVITY IN DELIRIUM. 5422 03:32:15,160 --> 03:32:16,760 PARTICULARLY AS THE INFECTION 5423 03:32:16,760 --> 03:32:21,560 TAKES OR INJURY TAKES HOLD IT 5424 03:32:21,560 --> 03:32:23,160 OFTEN CLINICALLY SEE THIS 5425 03:32:23,160 --> 03:32:24,560 DISCONNECT WHERE SYSTEMIC 5426 03:32:24,560 --> 03:32:26,360 PROCESSES RESOLVE BUT PATIENT 5427 03:32:26,360 --> 03:32:30,120 REMAINS PERSISTENTLY DELIRIOUS. 5428 03:32:30,120 --> 03:32:32,000 THAT MIGHT REFLECT THIS ONGOING 5429 03:32:32,000 --> 03:32:34,640 FEET FORWARD MECHANISM WITHIN 5430 03:32:34,640 --> 03:32:37,640 THE BRAIN MEDIATED BY REACTIVE 5431 03:32:37,640 --> 03:32:38,600 MICROGLIA. RELATED TO THAT WE 5432 03:32:38,600 --> 03:32:39,800 NEED TO LOOK AT DIFFERENCE 5433 03:32:39,800 --> 03:32:40,800 BETWEEN INFECTION AND HOST 5434 03:32:40,800 --> 03:32:44,040 IMMUNE RESPONSES IN DELIRIUM 5435 03:32:44,040 --> 03:32:47,040 VERY FOCUSED ON TREATING 5436 03:32:47,040 --> 03:32:48,480 INFECTION WHEN AS AN APPROACH 5437 03:32:48,480 --> 03:32:49,800 TREATING DELIRIUM BUT OBVIOUSLY 5438 03:32:49,800 --> 03:32:51,680 THAT MIGHT NOT BE THE FULL 5439 03:32:51,680 --> 03:32:53,240 STORY, THE HOST IMMUNE RESPONSE 5440 03:32:53,240 --> 03:32:55,880 WE NEED TO BE MODULATED AND 5441 03:32:55,880 --> 03:32:57,560 PERHAPS EVEN TREATMENT FOR 5442 03:32:57,560 --> 03:32:58,520 INFECTION SOMETIMES MAYBE WORSE 5443 03:32:58,520 --> 03:33:01,280 FOR DELIRIUM AND SO THAT RISK 5444 03:33:01,280 --> 03:33:03,640 BALANCE NEEDS TO BE ASSESSED. 5445 03:33:03,640 --> 03:33:06,160 AS MENTIONED BY PRIOR SPEAKERS 5446 03:33:06,160 --> 03:33:07,840 EVALUATE BLOOD AND PHYSIOLOGICAL 5447 03:33:07,840 --> 03:33:09,640 MARKERS IN DELIRIUM ONES THAT 5448 03:33:09,640 --> 03:33:10,920 AUTOMATE THE PROCESS AND REMOVE 5449 03:33:10,920 --> 03:33:13,080 THE BURDEN OF DIAGNOSIS AND 5450 03:33:13,080 --> 03:33:14,960 DETECTION IN THE ICU SO 5451 03:33:14,960 --> 03:33:18,280 TREATMENTS CAN BE IMPLEMENTED ON 5452 03:33:18,280 --> 03:33:20,000 A MORE TIMELY BASIS. SO IF THERE 5453 03:33:20,000 --> 03:33:22,760 IS ONE HIGH RISK HIGH REWARD 5454 03:33:22,760 --> 03:33:24,400 STUDY, A PROSPECTIVE CLINICAL 5455 03:33:24,400 --> 03:33:28,560 TRIAL OF IL 6 TRANSITIONNALLING 5456 03:33:28,560 --> 03:33:31,600 INHIBITION AND HUE FOR YOUR 5457 03:33:31,600 --> 03:33:33,680 ATTENTION -- THANK YOU FOR YOUR 5458 03:33:33,680 --> 03:33:34,560 ATTENTION. T HAPPY TO TAKE 5459 03:33:34,560 --> 03:33:45,040 QUESTIONS. DELIRIUM IS A RISK 5460 03:34:01,520 --> 03:34:02,520 FACTOR FOR POOR OUTCOMES AFTER 5461 03:34:02,520 --> 03:34:05,080 ARDS. BUT IS THERE A MECHANISTIC 5462 03:34:05,080 --> 03:34:05,440 LINK THERE? ? 5463 03:34:05,440 --> 03:34:08,200 >> I DO. THE CONNECTION BETWEEN 5464 03:34:08,200 --> 03:34:10,840 THE TWO MAY BE ACTUALLY 5465 03:34:10,840 --> 03:34:13,720 INACTIVATED MICROGLIA AN 5466 03:34:13,720 --> 03:34:14,520 NEUROTOXIC PHENOTYPES THAT ARE 5467 03:34:14,520 --> 03:34:17,760 OF MICROGLIA THAT BASICALLY SET 5468 03:34:17,760 --> 03:34:19,640 THE STAGE FOR LONG TERM 5469 03:34:19,640 --> 03:34:23,560 NEURODEGENERATION. SO CERTAINLY 5470 03:34:23,560 --> 03:34:24,960 NEED DO THAT AND LOOK AT THESE 5471 03:34:24,960 --> 03:34:28,960 PATIENT COHORT. ONE ASPECT OF IT 5472 03:34:28,960 --> 03:34:30,720 OR ADVANTAGE OF DOING A CLINICAL 5473 03:34:30,720 --> 03:34:33,600 TRIAL WITH IL 6 INHIBITOR IS 5474 03:34:33,600 --> 03:34:37,760 LOOK AT LONGER TERM OUTCOMES. 5475 03:34:37,760 --> 03:34:39,840 >> IT IS MY PLEASURE TO 5476 03:34:39,840 --> 03:34:40,880 INTRODUCE THE FOURTH SPEAKER IN 5477 03:34:40,880 --> 03:34:45,880 OUR SESSION. DR. TAREK SHARSHAR. 5478 03:34:45,880 --> 03:34:53,560 DR. SHARSHAR IS JOINING US FROM 5479 03:34:53,560 --> 03:34:55,320 PARIS, HEAD OF NEUROINTENSIVE 5480 03:34:55,320 --> 03:35:00,040 CARE UNIT AT THE POLE OF GHU 5481 03:35:00,040 --> 03:35:02,000 PSYCHIATRY AND NEUROSCIENCE 5482 03:35:02,000 --> 03:35:03,720 INSTITUTE. HE HAS BACKGROUND 5483 03:35:03,720 --> 03:35:06,040 BOTH IN NEUROLOGY AND INTENSIVE 5484 03:35:06,040 --> 03:35:09,080 CARE MEDICINE AND SUPERVISES A 5485 03:35:09,080 --> 03:35:10,640 MULTI-DISCIPLINARY EFFORT TO 5486 03:35:10,640 --> 03:35:13,240 UNDERSTAND PHENOTYPES OF BRAIN 5487 03:35:13,240 --> 03:35:15,520 INJURY IN THE SETTING OF SEPSIS 5488 03:35:15,520 --> 03:35:18,200 ARDS AND OTHER FORMS OF CRITICAL 5489 03:35:18,200 --> 03:35:19,520 ILLNESS. DR. SHARSHAR, THANK YOU 5490 03:35:19,520 --> 03:35:21,400 FOR JOINING US. 5491 03:35:21,400 --> 03:35:24,640 >> THANK YOU, VERY MUCH. I'M 5492 03:35:24,640 --> 03:35:29,680 VERY GRATEFUL TO THE NIH FOR THE 5493 03:35:29,680 --> 03:35:31,000 KIND INVITATION TO THIS VERY 5494 03:35:31,000 --> 03:35:32,280 STIMULATE LATING WORKSHOP. THERE 5495 03:35:32,280 --> 03:35:34,160 IS A GREAT HONOR FOR ME. I DON'T 5496 03:35:34,160 --> 03:35:36,720 SEE MY SLIDES SO I DON'T KNOW IF 5497 03:35:36,720 --> 03:35:47,160 I HAVE TO PULL UP THEM. 5498 03:35:51,000 --> 03:35:52,760 SO WE SIGH BRAIN DISFUNCTION IN 5499 03:35:52,760 --> 03:35:54,320 CRITICAL I WILL PATIENTS. WE 5500 03:35:54,320 --> 03:35:56,680 HAVE INDIVIDUALIZED FREE 5501 03:35:56,680 --> 03:36:00,280 PHENOTYPES INCLUDING SICKNESS 5502 03:36:00,280 --> 03:36:03,120 BEHAVIOR, CAPABILITY IN TERMS OF 5503 03:36:03,120 --> 03:36:06,520 COMA, AND PARTICULAR CONDITION 5504 03:36:06,520 --> 03:36:11,760 OF (INAUDIBLE) PATIENT, TRY 5505 03:36:11,760 --> 03:36:15,360 PHENOTYPES AN RELATIONSHIPS WITH 5506 03:36:15,360 --> 03:36:17,560 THE PSYCHOCONNECTIVE AND 5507 03:36:17,560 --> 03:36:18,480 (INAUDIBLE) OUTCOMES. I WILL 5508 03:36:18,480 --> 03:36:22,000 FOCUS ON THE FIRST AND THIRD 5509 03:36:22,000 --> 03:36:30,040 PHENOTYPES. BY MY COLLEAGUES. 5510 03:36:30,040 --> 03:36:33,480 THIS IS FROM SICKNESS BEHAVIOR 5511 03:36:33,480 --> 03:36:35,840 WHICH (INAUDIBLE) NEUROENDOCRINE 5512 03:36:35,840 --> 03:36:38,480 AUTONOMIC SYSTEMS. 5513 03:36:38,480 --> 03:36:39,280 PSYCHOLOGICAL DISORDERS 5514 03:36:39,280 --> 03:36:45,560 INCLUDING ANXIETY (INAUDIBLE). 5515 03:36:45,560 --> 03:36:47,320 SICKNESS BEHAVIOR IS A MAYOR 5516 03:36:47,320 --> 03:36:49,360 HIGHLY PRESERVED ADAPTIVE 5517 03:36:49,360 --> 03:36:51,400 RESPONSE TO PERIPHERAL 5518 03:36:51,400 --> 03:36:54,000 INFORMATION, RELATED TO 5519 03:36:54,000 --> 03:36:55,560 INFECTION. IT IS CHARACTERIZED 5520 03:36:55,560 --> 03:36:57,600 BY STEREOTYPE CALLED CHANGES IN 5521 03:36:57,600 --> 03:36:59,600 BEHAVIOR WHICH WE HAVE 5522 03:36:59,600 --> 03:37:05,240 EXPERIENCE IN OUR LIFE. THESE 5523 03:37:05,240 --> 03:37:06,400 CHANGES ARE SPECIFIC ACT 5524 03:37:06,400 --> 03:37:08,480 INVESTIGATION OF NEUROENDOCRINE 5525 03:37:08,480 --> 03:37:09,760 SYSTEM WHICH ARE (INAUDIBLE) 5526 03:37:09,760 --> 03:37:17,840 AXIS THAT ALLOWS NERVOUS SYSTEM 5527 03:37:17,840 --> 03:37:20,200 THE LIMB MIC BIC AND AUTONOMIC 5528 03:37:20,200 --> 03:37:21,600 NERVOUS SYSTEM ARE DIVIDED BY 5529 03:37:21,600 --> 03:37:26,920 TWO PATHWAYS. THE HUMORAL 5530 03:37:26,920 --> 03:37:28,640 PATHWAY, WHICH ARE LOCATING THE 5531 03:37:28,640 --> 03:37:33,720 VICINITY OF THE NEUROENDOCRINE 5532 03:37:33,720 --> 03:37:35,800 METABOLOMIC (INAUDIBLE) 5533 03:37:35,800 --> 03:37:42,400 RESPECTIVELY. LY PH INFLAMMATORY 5534 03:37:42,400 --> 03:37:45,000 MEDIATION OF THE BLOOD TO 5535 03:37:45,000 --> 03:37:49,480 NEUROENDOCRINE (INAUDIBLE). THE 5536 03:37:49,480 --> 03:37:51,600 NEURAL PATHWAY INVOLVED NERVE 5537 03:37:51,600 --> 03:37:53,400 WHICH DETECTS LOCAL INFLAMMATION 5538 03:37:53,400 --> 03:37:59,120 THAT CONTROL IT. IT PLAY AS SHE 5539 03:37:59,120 --> 03:38:03,400 SURABLE ROLE IN (INAUDIBLE). 5540 03:38:03,400 --> 03:38:06,200 THIS IS A MATURE MOUSE AUTONOMIC 5541 03:38:06,200 --> 03:38:07,800 LIMB BIC SYSTEM, AS YOU CAN SEE 5542 03:38:07,800 --> 03:38:10,680 THERE ARE HIGHLY INTERCONNECTED. 5543 03:38:10,680 --> 03:38:11,960 WE HAVE PARTICULARLY INTERESTED 5544 03:38:11,960 --> 03:38:14,680 IN THE AMYGDALA WHICH IS A 5545 03:38:14,680 --> 03:38:17,480 COMPONENT OF THE LIMBIC SYSTEM. 5546 03:38:17,480 --> 03:38:19,920 THE COMPLEX OF THE (INAUDIBLE) 5547 03:38:19,920 --> 03:38:24,320 NUCLEUS STRUCTURE WHICH CONTROLS 5548 03:38:24,320 --> 03:38:28,760 BLOOD PRESSURE IN THE AMYGDALA. 5549 03:38:28,760 --> 03:38:33,440 THIS IS A REALLY SCHEMATIC VIEW 5550 03:38:33,440 --> 03:38:35,520 OF NEURAL SIGNALING DYSFUNCTION 5551 03:38:35,520 --> 03:38:38,120 AT ANY LABEL, ANY DYSFUNCTION 5552 03:38:38,120 --> 03:38:44,240 RESULT IN MAL ADAPTIVE BEHAVIOR, 5553 03:38:44,240 --> 03:38:46,960 THESE CAN BE THE CASE OF ANXIETY 5554 03:38:46,960 --> 03:38:51,320 . WE HAVE ASSESSED 5555 03:38:51,320 --> 03:38:53,320 RELATIONSHIP BETWEEN ANXIETY AT 5556 03:38:53,320 --> 03:38:57,400 ICU ADMISSION AND OCCURRENCE OF 5557 03:38:57,400 --> 03:38:59,680 ORGAN -- FIRST SEVIN DAYS AND 5558 03:38:59,680 --> 03:39:03,720 ANXIETY WAS CONSIDERED MODERATE 5559 03:39:03,720 --> 03:39:06,480 WHEN THE CITRATE SCALE WAS ABOVE 5560 03:39:06,480 --> 03:39:14,440 40 OUT OF 80. WE FOUND ANXIETY 5561 03:39:14,440 --> 03:39:19,040 WAS ASSOCIATED WITH ORGANS THAT 5562 03:39:19,040 --> 03:39:22,680 ARE PARTICULAR SEVERITY OF 5563 03:39:22,680 --> 03:39:27,640 TESTIFY SCORE. IN ANCILLARY 5564 03:39:27,640 --> 03:39:29,000 STUDY WE ASSESS MANY FIERCE OF 5565 03:39:29,000 --> 03:39:34,920 THESE PATIENTS ADMITTED IN ICU. 5566 03:39:34,920 --> 03:39:36,480 WE FOUND ABSENCE OF FEAR OF 5567 03:39:36,480 --> 03:39:38,000 DYING WAS ASSOCIATED WITH ORGAN 5568 03:39:38,000 --> 03:39:41,240 FAILURE ALONG WITH INTENSITY OF 5569 03:39:41,240 --> 03:39:45,760 ANXIETY SITE AND SCALE. SO THE 5570 03:39:45,760 --> 03:39:51,080 QUESTION, WHAT IS THE MECHANISMS 5571 03:39:51,080 --> 03:39:54,640 UNDERLYING (INAUDIBLE). NEXT 5572 03:39:54,640 --> 03:40:00,520 SLIDE. IMPAIRMENT OF 5573 03:40:00,520 --> 03:40:01,400 INTERCEPTION OR -- WHICH PLAY A 5574 03:40:01,400 --> 03:40:04,120 MAJOR ROLE IN BEHAVIORAL DANGER 5575 03:40:04,120 --> 03:40:06,560 AND TO STRESS. IS THERE ANY 5576 03:40:06,560 --> 03:40:12,880 HUMAN FOR ACUTE DYSFUNCTION, 5577 03:40:12,880 --> 03:40:17,600 YES, BRIEFLY WE HAVE SEPSIS 5578 03:40:17,600 --> 03:40:24,720 INDUCES INACTIVATION OF -- 5579 03:40:24,720 --> 03:40:27,480 FEATURES IN PATH LOGICAL 5580 03:40:27,480 --> 03:40:30,520 RECORDING, MOREOVER WE FELT THAT 5581 03:40:30,520 --> 03:40:33,000 PHARMACO PHARMACO GENOMICS OF 5582 03:40:33,000 --> 03:40:33,560 PHARMACOLOGICAL (INAUDIBLE) 5583 03:40:33,560 --> 03:40:39,080 SPECIFIC INHIBITION PREVENTS 5584 03:40:39,080 --> 03:40:42,000 OCCURRENCE OF PTSD BEHAVIOR IN A 5585 03:40:42,000 --> 03:40:48,720 MOUSE (INAUDIBLE) IN CONCLUSION 5586 03:40:48,720 --> 03:40:51,800 THERE'S EVIDENCE FOR ACUTE 5587 03:40:51,800 --> 03:40:52,960 AMYGDALA DYSFUNCTION IMPAIRED 5588 03:40:52,960 --> 03:40:54,640 PERCEPTION OF DANGER THAT MIGHT 5589 03:40:54,640 --> 03:40:57,680 CONTRIBUTE TO SOMATIC 5590 03:40:57,680 --> 03:41:01,160 DETERIORATION BY IMPAIRMENT OF 5591 03:41:01,160 --> 03:41:03,760 FEAR. WHICH ALSO RESULTSES IN 5592 03:41:03,760 --> 03:41:06,280 PTSD BY INACTIVATION OF FEAR 5593 03:41:06,280 --> 03:41:09,040 CIRCUIT. WE ARE CURRENTLY 5594 03:41:09,040 --> 03:41:13,440 INVESTIGATING WHETHER EARLY 5595 03:41:13,440 --> 03:41:17,480 AMYGDALA OF GAY VALUE NERVE. 5596 03:41:17,480 --> 03:41:19,040 PHARMACOLOGICAL AND 5597 03:41:19,040 --> 03:41:21,080 NON-PHARMACOLOGICAL APPROACH 5598 03:41:21,080 --> 03:41:22,880 PREVENTS INAPPROPRIATE EARLY 5599 03:41:22,880 --> 03:41:25,000 AMYGDALA ACTIVATION. IN THE. 5600 03:41:25,000 --> 03:41:28,280 ING MONTHS WE WILL CARRY OUT A 5601 03:41:28,280 --> 03:41:29,240 RANDOMIZED CLINICAL TRIAL IN 5602 03:41:29,240 --> 03:41:32,760 SEPTIC SHOCK PATIENT IN ORDER TO 5603 03:41:32,760 --> 03:41:35,840 INCREASE OUTCOME BY THREE DAYS 5604 03:41:35,840 --> 03:41:37,520 BUT ALSO MODULATE MICROGLIAL 5605 03:41:37,520 --> 03:41:42,520 ACTIVATION. AND DIRECTION OF 5606 03:41:42,520 --> 03:41:47,920 PTSD. -- REDUCTION OF PTSD. THEN 5607 03:41:47,920 --> 03:41:53,880 BEGIN IN 7 DAYS. NEXT SLIDE. SO 5608 03:41:53,880 --> 03:41:57,720 WE NOW BETWEEN DEEP SEDATION AND 5609 03:41:57,720 --> 03:42:00,880 THAT INVOLVE THE BRAIN STEM 5610 03:42:00,880 --> 03:42:05,200 DYSFUNCTION. THERE ARE MANY 5611 03:42:05,200 --> 03:42:08,040 MAJOR CHALLENGES IN DEEP SEDATED 5612 03:42:08,040 --> 03:42:10,680 PATIENTS. HOW DO -- WHAT CAN WE 5613 03:42:10,680 --> 03:42:15,920 DETAIL BRAIN DYSFUNCTION, IN 5614 03:42:15,920 --> 03:42:18,920 PATIENT, POSITIVE SEDATION ON 5615 03:42:18,920 --> 03:42:22,480 WHY DEEP SEDATION IS ASSOCIATED 5616 03:42:22,480 --> 03:42:24,520 WITH INCREASED MORTALITY. WE 5617 03:42:24,520 --> 03:42:27,440 WERE INTERESTED IN ASSESSING 5618 03:42:27,440 --> 03:42:34,440 WHETHER NEUROINFLAMMATION IS 5619 03:42:34,440 --> 03:42:40,760 INFORMATIVE (INAUDIBLE) HAS 5620 03:42:40,760 --> 03:42:44,080 SHOWN NOT AFFECT BRAIN STEM -- 5621 03:42:44,080 --> 03:42:49,840 NEXT SLIDE COHORT SOME BRAIN 5622 03:42:49,840 --> 03:42:53,600 STEM REFLECTS LESS THAN OTHERS 5623 03:42:53,600 --> 03:42:57,120 INCLUDING THE LIGHT REFLECT 5624 03:42:57,120 --> 03:42:59,960 CORNEAL REFLECT NEXT SLIDE. WE 5625 03:42:59,960 --> 03:43:04,200 FOUND THE B A SENSES OF 5626 03:43:04,200 --> 03:43:06,680 (INAUDIBLE) REFLECTS 5627 03:43:06,680 --> 03:43:12,000 INDEPENDENTLY ASSOCIATED WITH 5628 03:43:12,000 --> 03:43:13,840 MORTALITY AND (INAUDIBLE) 5629 03:43:13,840 --> 03:43:17,200 RESPECTIVELY. NEXT SLIDE. OUR 5630 03:43:17,200 --> 03:43:19,840 FIRST FINDING SHOWED THAT 5631 03:43:19,840 --> 03:43:22,800 NEUROLOGICAL EXAMINATION IN DEEP 5632 03:43:22,800 --> 03:43:24,280 SEDATED PATIENTS WAS FEASIBLE 5633 03:43:24,280 --> 03:43:27,320 REPRODUCIBLE AND INTERPRETABLE 5634 03:43:27,320 --> 03:43:30,360 PHARMACOLOGICAL SIDE. BUT ALSO 5635 03:43:30,360 --> 03:43:33,080 ENABLES TO DETECT NECESSITY IN 5636 03:43:33,080 --> 03:43:37,000 TERMS OF PATIENT WAYS TO DEVELOP 5637 03:43:37,000 --> 03:43:42,080 DISCONTINUATION OF SEDATION. 5638 03:43:42,080 --> 03:43:43,840 THEN WE INVESTIGATED WHETHER 5639 03:43:43,840 --> 03:43:47,120 THERE WAS BRAIN STEM SYNDROME IN 5640 03:43:47,120 --> 03:43:48,480 REASON DEEPLY SEDATE CRITICALLY 5641 03:43:48,480 --> 03:43:51,480 ILL PATIENTS. NEUROLOGICAL 5642 03:43:51,480 --> 03:43:52,160 QUESTION BUT BECOMING 5643 03:43:52,160 --> 03:43:56,680 INTERESTING TO I DRESS. NEXT 5644 03:43:56,680 --> 03:43:57,880 SLIDE WE NAME OURSELVES THE -- 5645 03:43:57,880 --> 03:44:08,360 WE HAVE ASSESS IN 140 THE 2 5646 03:44:13,760 --> 03:44:16,760 PROFILES OF HALF PATIENT AGE, 5647 03:44:16,760 --> 03:44:18,800 THE RED ONE (INAUDIBLE) 5648 03:44:18,800 --> 03:44:20,600 HOMOGENOUS SEPARATION OF THE 5649 03:44:20,600 --> 03:44:22,240 BRAIN STEM REFLEXIA, MEANING 5650 03:44:22,240 --> 03:44:25,040 THEY ARE UNIFORMLY PRESENT OR 5651 03:44:25,040 --> 03:44:27,400 ABSENT TOGETHER. THE SECOND 5652 03:44:27,400 --> 03:44:29,280 PROFILE, BLUE ONE IS 5653 03:44:29,280 --> 03:44:31,600 CHARACTERIZED BY HETERO 5654 03:44:31,600 --> 03:44:33,560 ACTIVATION. THE BLUE PROFILE WAS 5655 03:44:33,560 --> 03:44:36,320 ASSOCIATED WITH INCREASE 5656 03:44:36,320 --> 03:44:38,080 MORTALITY WITH ISSUE ABOUT SIX. 5657 03:44:38,080 --> 03:44:44,720 NEXT SLIDE. THE RIGHT PROFILE, 5658 03:44:44,720 --> 03:44:47,760 MAINLY EFFECT OF OBSERVATION, 5659 03:44:47,760 --> 03:44:50,440 WHILE BLUE ONE REFLECTS BRAIN 5660 03:44:50,440 --> 03:44:53,080 STEM INSULT LIKELY 5661 03:44:53,080 --> 03:44:57,320 NEUROINFLAMMATORY FROM THE AREA 5662 03:44:57,320 --> 03:44:59,520 WHICH BEFORE MENTIONED 5663 03:44:59,520 --> 03:45:02,720 MEASURABLE ROLES AS REALLY -- 5664 03:45:02,720 --> 03:45:09,920 PATHWAYS. WE DEVELOPED BRAIN 5665 03:45:09,920 --> 03:45:12,240 STEM ASSESSMENT SCALE SCORING 5666 03:45:12,240 --> 03:45:13,760 THE DYSFUNCTION IN DEEPLY 5667 03:45:13,760 --> 03:45:15,920 SEDATEDDISH PAS. WE ARE 5668 03:45:15,920 --> 03:45:21,760 VALIDATING THE SCORE. 5669 03:45:21,760 --> 03:45:27,160 INTERESTINGLY WE FOUND THAT 5670 03:45:27,160 --> 03:45:28,920 INCREASE SCORE IN COVID ARDS 5671 03:45:28,920 --> 03:45:33,520 PATIENTS. AS YOU KNOW THE BRAIN 5672 03:45:33,520 --> 03:45:39,120 STEM IS AWAKENING THE OTHER 5673 03:45:39,120 --> 03:45:41,040 SYSTEM AND VITAL FUNCTION AND 5674 03:45:41,040 --> 03:45:43,840 IMMUNE RESIDENCY OF THE 5675 03:45:43,840 --> 03:45:45,120 AUTONOMIC NERVOUS S. THERE'S 5676 03:45:45,120 --> 03:45:50,960 BRODY OF -- BODY OF EVIDENCE, 5677 03:45:50,960 --> 03:45:54,440 ACTIVITY REFLECTING IN CELLULAR 5678 03:45:54,440 --> 03:45:56,120 DYSFUNCTION OF ACTIVITY SYSTEM 5679 03:45:56,120 --> 03:45:59,000 WHICH MAY CONTRIBUTE TO THE 5680 03:45:59,000 --> 03:46:02,840 AWAKENING OF THE (INAUDIBLE). 5681 03:46:02,840 --> 03:46:04,640 IMPAIRED HEART RATE VARIABILITY 5682 03:46:04,640 --> 03:46:08,200 CONTROLLED BY AMYGDALA IS 5683 03:46:08,200 --> 03:46:09,080 ASSOCIATED WITH MORTALITY AND 5684 03:46:09,080 --> 03:46:12,600 ORGAN FAILURE. IT HAS BEEN SHOWN 5685 03:46:12,600 --> 03:46:14,560 THAT VARIABILITY OF (INAUDIBLE) 5686 03:46:14,560 --> 03:46:20,920 IS ASSOCIATED WITH (INAUDIBLE). 5687 03:46:20,920 --> 03:46:26,480 IT HAS BEEN SHOWN THAT THERE IS 5688 03:46:26,480 --> 03:46:32,240 SHORT CONNECTION OF THE ESS AND 5689 03:46:32,240 --> 03:46:34,240 PATHOLOGICAL STUDIES EVIDENCE 5690 03:46:34,240 --> 03:46:35,480 NEUROINFLAMMATION AN NEURONAL 5691 03:46:35,480 --> 03:46:37,680 APOP STOWSIS BUT ALSO MICROGLIAL 5692 03:46:37,680 --> 03:46:43,920 A APOPTOSIS SYSTEM AND THE THE 5693 03:46:43,920 --> 03:46:45,920 AUTONOMIC (INAUDIBLE). NEXT 5694 03:46:45,920 --> 03:46:49,360 SLIDE. WE HAVE JUST ACHIEVED A 5695 03:46:49,360 --> 03:46:52,240 MULTI-CENTER OBSERVATIONAL 5696 03:46:52,240 --> 03:46:55,480 STUDY. TO DETERMINE WHETHER 5697 03:46:55,480 --> 03:46:58,960 POTENCY VALUE OF P 1478 5698 03:46:58,960 --> 03:47:04,360 RESISTANCE OF THE SA -- SSEP, IT 5699 03:47:04,360 --> 03:47:07,760 IS GENERATED BY AMYGDALA. AND WE 5700 03:47:07,760 --> 03:47:10,240 FOUND INCREASE LATENCY OF P 14 5701 03:47:10,240 --> 03:47:14,440 WAS ASSOCIATED WITH INCREASE 5702 03:47:14,440 --> 03:47:18,920 MORTALITY AND CRITICAL SEVERITY 5703 03:47:18,920 --> 03:47:20,320 PRESERVATION AND PRIMARY BRAIN 5704 03:47:20,320 --> 03:47:21,800 INJURY SO WE THINK THIS IS IN 5705 03:47:21,800 --> 03:47:23,400 SOME WAY PROOF THAT THERE IS A 5706 03:47:23,400 --> 03:47:25,640 BRAIN SCAN DYSFUNCTION OF THE 5707 03:47:25,640 --> 03:47:33,400 THE AMYGDALA. AND IN CONCLUSION, 5708 03:47:33,400 --> 03:47:35,920 THERE IS EVIDENCE FOR BRAIN STEM 5709 03:47:35,920 --> 03:47:39,160 DYSFUNCTION IN DECREASING ATP IN 5710 03:47:39,160 --> 03:47:40,600 PATIENT INCLUDING PATTERNS OF 5711 03:47:40,600 --> 03:47:43,200 BRAIN STEM REFLEXES ABOLITION, 5712 03:47:43,200 --> 03:47:45,400 IMPAIRED NEUROPHYSIOLOGICAL 5713 03:47:45,400 --> 03:47:48,320 RESPONSE, IMPAIRED BRAIN STEM 5714 03:47:48,320 --> 03:47:52,440 OUTPUT HEART RATE VARIABILITY 5715 03:47:52,440 --> 03:47:57,360 AND MAYBE SOME WE KNOW IMPORTANT 5716 03:47:57,360 --> 03:48:00,560 OF THE NEUROPATHOLOGICAL 5717 03:48:00,560 --> 03:48:03,200 FINDINGS. EVIDENCE FOR PROCESS 5718 03:48:03,200 --> 03:48:05,280 ORIGINATING FROM THE BRAIN STEM 5719 03:48:05,280 --> 03:48:08,240 DYSFUNCTION AND EVIDENCE FOR 5720 03:48:08,240 --> 03:48:09,240 NEUROINFLAMMATORY PROCESS 5721 03:48:09,240 --> 03:48:13,600 ORIGINATING FROM THE AREA 5722 03:48:13,600 --> 03:48:16,480 POSTREMA. SO WHAT I WILL GAPS I 5723 03:48:16,480 --> 03:48:19,400 THINK THE MAIN GAPS WE HAVE 5724 03:48:19,400 --> 03:48:21,680 REALLY UNDERSTANDING OF BETTER 5725 03:48:21,680 --> 03:48:24,320 GENETIC MECHANISMS OF BRAIN 5726 03:48:24,320 --> 03:48:25,840 DYSFUNCTION AND ITS COURSE 5727 03:48:25,840 --> 03:48:28,600 TOWARD LONG TERM PSYCHOCOGNITIVE 5728 03:48:28,600 --> 03:48:33,240 DYSFUNCTION. BUT ALSO MAYBE WE 5729 03:48:33,240 --> 03:48:39,560 SHOULD PROMOTE A CHANCE BETWEEN 5730 03:48:39,560 --> 03:48:43,040 PRIMARY (INAUDIBLE) WE HAVE MANY 5731 03:48:43,040 --> 03:48:48,000 OPPORTUNITIES AND I THINK THAT 5732 03:48:48,000 --> 03:48:50,480 WE CAN SHOULD PROBABLY REACH A 5733 03:48:50,480 --> 03:48:52,680 MODEL APPROACH. WE HAVE INCLUDE 5734 03:48:52,680 --> 03:48:56,000 REFINE PHENOTYPING OF ACUTE 5735 03:48:56,000 --> 03:48:57,600 BRAIN DYSFUNCTION BASED ON 5736 03:48:57,600 --> 03:49:01,720 NEUROANATOMICAL APPROACH AND 5737 03:49:01,720 --> 03:49:04,280 CLINICAL RESEARCH NEUROLOGICAL 5738 03:49:04,280 --> 03:49:06,640 MODELS. TRANSLATIONAL RESEARCH 5739 03:49:06,640 --> 03:49:08,360 AND WE HAVE AT OUR DISPOSAL 5740 03:49:08,360 --> 03:49:09,920 VALIDATED EXPERIMENTAL MODELS 5741 03:49:09,920 --> 03:49:12,120 AND SOPHISTICATED EXPERIMENTAL 5742 03:49:12,120 --> 03:49:15,960 TECHNIQUES. AND I THINK THAT WE 5743 03:49:15,960 --> 03:49:20,200 SHOULD CARRY OUT PHARMACOLOGICAL 5744 03:49:20,200 --> 03:49:21,960 CLINICAL TRIALS BASED ON ROBUST 5745 03:49:21,960 --> 03:49:27,320 PRE-CLINICAL EVIDENCE. NEXT 5746 03:49:27,320 --> 03:49:31,800 SLIDE. SO HIGH RISK HIGH REWARD 5747 03:49:31,800 --> 03:49:33,080 ING IDEAS IS DEVELOPING A 5748 03:49:33,080 --> 03:49:34,360 DETECTION TOOL OF BRAIN STEM 5749 03:49:34,360 --> 03:49:35,880 DYSFUNCTION APPLICABLE AT 5750 03:49:35,880 --> 03:49:38,560 BEDSIDE. DELINEATING ADAPTIVE 5751 03:49:38,560 --> 03:49:40,600 FROM MAL ADAPTIVE RESPONSE TO 5752 03:49:40,600 --> 03:49:44,280 STRESS. INCLUDING MALADAPTIVE 5753 03:49:44,280 --> 03:49:46,640 PSYCHOLOGICAL RESPONSE. AND 5754 03:49:46,640 --> 03:49:47,840 RESTORING THE LUNG GUT BRAIN 5755 03:49:47,840 --> 03:49:52,640 AXIS. THIS IS JUST AN 5756 03:49:52,640 --> 03:49:57,200 ADVERTISEMENTED, VERY HAPPY TO 5757 03:49:57,200 --> 03:49:59,880 WELCOME YOU TO SYMPOSIUM IN ICU. 5758 03:49:59,880 --> 03:50:04,000 NEXT SLIDE. FINALLY I WOULD 5759 03:50:04,000 --> 03:50:10,000 LIKE TO THANK ALL MY FRIENDS AND 5760 03:50:10,000 --> 03:50:16,120 COLLEAGUE FROM INSTITUTE PASTEUR 5761 03:50:16,120 --> 03:50:17,800 AND ASSISTANCE HOSPITAL PUBLIC 5762 03:50:17,800 --> 03:50:19,560 DEPARIS. THANK YOU FOR YOUR 5763 03:50:19,560 --> 03:50:20,160 ATTENTION. READY TO TAKE ANY 5764 03:50:20,160 --> 03:50:25,720 QUESTIONS. 5765 03:50:25,720 --> 03:50:26,440 >> THANK YOU VERY MUCH. I WILL 5766 03:50:26,440 --> 03:50:28,400 START WITH A QUESTION, RELATED 5767 03:50:28,400 --> 03:50:30,200 TO WORK YOU ARE DOING ON BRAIN 5768 03:50:30,200 --> 03:50:31,480 STEM DYSFUNCTION. I UNDERSTAND 5769 03:50:31,480 --> 03:50:33,680 WHY THAT IS VERY IMPORTANT FOR 5770 03:50:33,680 --> 03:50:35,680 PHENOTYPING ESPECIALLY DEEPLY 5771 03:50:35,680 --> 03:50:37,680 SEDATED PATIENTS. BUT AS WE 5772 03:50:37,680 --> 03:50:42,400 THINK ABOUT THE BROAD SPECTRUM 5773 03:50:42,400 --> 03:50:44,080 OF BRAIN BASED DYSFUNCTION OR 5774 03:50:44,080 --> 03:50:46,320 DISABILITY THAT PATIENTS 5775 03:50:46,320 --> 03:50:47,640 EXPERIENCE DO YOU THINK THAT 5776 03:50:47,640 --> 03:50:49,160 PHENOTYPE IS ALSO RELATED TO 5777 03:50:49,160 --> 03:50:51,200 SOME INJURY IN OTHER AREAS OF 5778 03:50:51,200 --> 03:50:54,200 THE BRAIN? IS THERE ANY EVIDENCE 5779 03:50:54,200 --> 03:50:56,800 OR -- FOR THAT? 5780 03:50:56,800 --> 03:50:59,360 >> YOU ASKING WHETHER THE 5781 03:50:59,360 --> 03:51:00,600 MECHANISMS THAT INVOLVE THE 5782 03:51:00,600 --> 03:51:02,280 BRAIN STEM ALSO PLAY A ROLE -- 5783 03:51:02,280 --> 03:51:04,640 YES, I THINK WHEN 5784 03:51:04,640 --> 03:51:05,880 NEUROINFLAMMATORY PROCESS IS NOT 5785 03:51:05,880 --> 03:51:07,200 ONLY RELATED TO THE BRAIN STEM, 5786 03:51:07,200 --> 03:51:10,480 IT HAS BEEN HOE IT CAN GO OVER 5787 03:51:10,480 --> 03:51:13,960 ALL PARTS OF BRAIN. MICROBIAL 5788 03:51:13,960 --> 03:51:16,680 ACTIVATION IS EVIDENCE IN 5789 03:51:16,680 --> 03:51:18,960 VARIOUS MODEL, SEPSIS MODELS BUT 5790 03:51:18,960 --> 03:51:22,040 ALSO SHOWN ON NEUROPATHOLOGICAL 5791 03:51:22,040 --> 03:51:24,400 STUDIES, LONG TIME AGO WE HAVE 5792 03:51:24,400 --> 03:51:25,800 NEUROPATHOLOGICAL STUDY OF 5793 03:51:25,800 --> 03:51:29,040 PATIENT DIE FROM SEPTIC SHOCK 5794 03:51:29,040 --> 03:51:31,480 AND FOUND THAT INACTIVATION OF 5795 03:51:31,480 --> 03:51:34,680 MICROGLIAL CELLS, INTERESTINGLY 5796 03:51:34,680 --> 03:51:36,280 IT WAS RATHER PARTICULAR AREAS 5797 03:51:36,280 --> 03:51:40,800 OF THE BRAIN, BRAIN STEM BUT 5798 03:51:40,800 --> 03:51:44,320 ALSO THE LIMBIC SYSTEM ALSO 5799 03:51:44,320 --> 03:51:47,200 FRONTAL LOBE. SO SEEMS THAT 5800 03:51:47,200 --> 03:51:51,520 THERE IS A NUMBER OF REACTIVITY, 5801 03:51:51,520 --> 03:51:55,200 MORE IN SOME PARTICULAR AREAS 5802 03:51:55,200 --> 03:51:58,760 WHICH COULD ACCOUNT FOR THE 5803 03:51:58,760 --> 03:52:00,880 PHENOTYPE, CLINICAL PHENOTYPES 5804 03:52:00,880 --> 03:52:02,840 AN LONG TERM PSYCHOLOGICAL 5805 03:52:02,840 --> 03:52:06,080 DISORDERS. WE -- REGARDING BRAIN 5806 03:52:06,080 --> 03:52:07,960 STEM DYSFUNCTION WE ILLUSTRATED 5807 03:52:07,960 --> 03:52:10,280 EVIDENCE IT IN THE DEEPLY 5808 03:52:10,280 --> 03:52:12,160 SEDATED PATIENTS BUT MAYBE CAN 5809 03:52:12,160 --> 03:52:13,560 PLAY A ROLE LONG-TERM 5810 03:52:13,560 --> 03:52:15,080 DISABILITY. WE KNOW WHEN THE 5811 03:52:15,080 --> 03:52:18,400 BRAIN STEM IS INVOLVED IN 5812 03:52:18,400 --> 03:52:19,640 PARKINSON DISEASE FOR INSTANCE, 5813 03:52:19,640 --> 03:52:22,960 IT CAN COME FROM MANY, MANY 5814 03:52:22,960 --> 03:52:26,920 SYMPTOMS LIKE FOG, LOCOMOTIVE 5815 03:52:26,920 --> 03:52:29,760 DISABILITY. SO MAYBE THERE IS A 5816 03:52:29,760 --> 03:52:31,360 SUB CLINICAL BRAIN STEM 5817 03:52:31,360 --> 03:52:36,040 DYSFUNCTION THAT CAN LAST FOR 5818 03:52:36,040 --> 03:52:42,520 SOME LONG TERM DISORDER. I DON'T 5819 03:52:42,520 --> 03:52:44,960 HAVE PROOF OF THAT. 5820 03:52:44,960 --> 03:52:50,120 >> ALL RIGHT. THANK YOU. I DON'T 5821 03:52:50,120 --> 03:52:51,360 THINK WE HAVE I HAVE BEEN COMING 5822 03:52:51,360 --> 03:52:52,920 QUESTIONS -- INCOMING QUESTIONS 5823 03:52:52,920 --> 03:52:54,880 FROM THE CHAT SO MAYBE 60 5824 03:52:54,880 --> 03:52:55,960 SECONDS EARLY WILL TURN TO THE 5825 03:52:55,960 --> 03:52:57,760 PANEL DISCUSSION AND TRY AND 5826 03:52:57,760 --> 03:53:02,440 SUMMARIZE THESE VERY INTERESTING 5827 03:53:02,440 --> 03:53:04,280 DIVERSE TALKS WE HEARD DURING 5828 03:53:04,280 --> 03:53:06,200 THE SESSION AND TURN BACK TO OUR 5829 03:53:06,200 --> 03:53:14,480 PANELISTS. SO SOME COMMON THEMES 5830 03:53:14,480 --> 03:53:14,880 EMERGING FROM THESE 5831 03:53:14,880 --> 03:53:18,280 PRESENTATIONS ARE ATTENTION 5832 03:53:18,280 --> 03:53:20,560 BETWEEN COMMON MECHANISMS AND 5833 03:53:20,560 --> 03:53:23,360 COMMON FINAL PATHWAYS THE 5834 03:53:23,360 --> 03:53:27,240 COMMONALITY BETWEEN BIOMARKERS 5835 03:53:27,240 --> 03:53:30,760 OF DELIRIUM IN URINARY TRACT 5836 03:53:30,760 --> 03:53:32,520 INFECTION AND VENTILATE TORR 5837 03:53:32,520 --> 03:53:35,440 INDUCED -- VENTILATOR INDUCED 5838 03:53:35,440 --> 03:53:36,880 THERAPY, CHEMOTHERAPY, CAR T 5839 03:53:36,880 --> 03:53:40,400 THERAPY AS WELL AS IN COVID, 5840 03:53:40,400 --> 03:53:43,320 VERSUS SOME OTHERS THAT MAYBE 5841 03:53:43,320 --> 03:53:46,280 MORE DISTINCTLY RELATED TO 5842 03:53:46,280 --> 03:53:50,720 INFECTION LIKE TAU AND OTHER 5843 03:53:50,720 --> 03:53:54,120 PRION LIKE PROTEINS INTRODUCED 5844 03:53:54,120 --> 03:53:56,880 INTO THE CIRCULATION. I WOULD 5845 03:53:56,880 --> 03:54:01,480 ALSO LIKE TO TOUCH ON ANOTHER 5846 03:54:01,480 --> 03:54:03,600 THEME EARLIER MAYBE START WITH 5847 03:54:03,600 --> 03:54:08,400 QUESTIONS FOR PANELISTS THERE, 5848 03:54:08,400 --> 03:54:10,520 ANOTHER COMMON THEME TO ALL WORK 5849 03:54:10,520 --> 03:54:12,640 PRESENTED IS WE AS 5850 03:54:12,640 --> 03:54:14,960 NEUROSCIENTISTS 5851 03:54:14,960 --> 03:54:17,320 NEUROIMMUNOLOGIST IMMUNOLOGISTS, 5852 03:54:17,320 --> 03:54:18,760 WORK WITH ANIMALS A DISTINCT 5853 03:54:18,760 --> 03:54:22,680 TOOL KIT DESIGNED TO TRY AND 5854 03:54:22,680 --> 03:54:25,360 LOCALIZE BRAIN DYSFUNCTION TO 5855 03:54:25,360 --> 03:54:30,040 UNDERSTAND NEUROAN TOM INC. 5856 03:54:30,040 --> 03:54:31,560 BASIS OF BEHAVIOR. WE HEARD A 5857 03:54:31,560 --> 03:54:36,760 LOT THIS MORNING ABOUT 5858 03:54:36,760 --> 03:54:38,280 QUESTIONING WHETHER TOOL KITS WE 5859 03:54:38,280 --> 03:54:40,920 USE ARE REFLECTING THE 5860 03:54:40,920 --> 03:54:47,000 EXPERIENCE OF PATIENTS AND TRULY 5861 03:54:47,000 --> 03:54:48,200 FUNCTIONAL OUTCOMES IMPORTANT 5862 03:54:48,200 --> 03:54:50,120 FOR SURVIVORS OF ARDS. TURN THAT 5863 03:54:50,120 --> 03:54:52,680 QUESTION ASKED ABOUT CLINICAL 5864 03:54:52,680 --> 03:54:54,160 OUTCOMES AND MEASUREMENTS TOOLS 5865 03:54:54,160 --> 03:54:55,840 BACK TO THE PANEL AND ASK DO WE 5866 03:54:55,840 --> 03:54:58,280 THINK THERE IS SPACE WITHIN THE 5867 03:54:58,280 --> 03:54:59,880 MODELS WE ARE USING AND THE WAY 5868 03:54:59,880 --> 03:55:05,800 WE ASK OUR QUESTIONS TO PERHAPS 5869 03:55:05,800 --> 03:55:09,560 BE MORE FOCUSED ON FUNCTIONAL 5870 03:55:09,560 --> 03:55:11,320 OUTCOMES, THAT MAYBE RELEVANT TO 5871 03:55:11,320 --> 03:55:15,640 ARDS SURVIVORS RATHER THAN THE 5872 03:55:15,640 --> 03:55:17,120 CLASSICAL TOOLS WE HAVE USED, 5873 03:55:17,120 --> 03:55:21,560 THAT FOCUS ON REALLY STRONG 5874 03:55:21,560 --> 03:55:24,440 CORRELATIONS BETWEEN BEHAVIOR 5875 03:55:24,440 --> 03:55:34,920 AND NEUROANATOMY. ONE EXAMPLE 5876 03:55:36,520 --> 03:55:40,400 WE MIGHT THINK OF IS -- SORRY, 5877 03:55:40,400 --> 03:55:43,560 MICHELLE YOU ARE UNMUTING. 5878 03:55:43,560 --> 03:55:45,760 >> I WOULD LOVE TO HEAR YOUR 5879 03:55:45,760 --> 03:55:48,800 EXAMPLE BUT TO ACKNOWLEDGE THIS 5880 03:55:48,800 --> 03:55:51,200 EMERGING THEME, SEEMS THERE ARE 5881 03:55:51,200 --> 03:55:52,520 COMMONALITIES ACROSS IMMUNE 5882 03:55:52,520 --> 03:55:55,320 CHALLENGES AFFECTING THE NERVOUS 5883 03:55:55,320 --> 03:55:55,920 SYSTEM, THAT MIGHT BE SIMILAR 5884 03:55:55,920 --> 03:55:57,960 SYMPTOMS THAT PEOPLE EXPERIENCE 5885 03:55:57,960 --> 03:56:02,480 AFTER CANCER THERAPY, AFTER UTI 5886 03:56:02,480 --> 03:56:06,480 AFTER LUNG INFECTION; WE SEE 5887 03:56:06,480 --> 03:56:09,720 COMMON SYNDROME THAT IS VARYING 5888 03:56:09,720 --> 03:56:15,000 SEVERITY BUT SEDUCING TO BE 5889 03:56:15,000 --> 03:56:17,640 PATHOGENS SPECIFIC 5890 03:56:17,640 --> 03:56:19,120 NEUROBIOLOGICAL CHANGES AND 5891 03:56:19,120 --> 03:56:20,480 SPECIFIC MECHANISMS ONE MIGHT 5892 03:56:20,480 --> 03:56:22,480 SEE IN ARDS THAT YOU DON'T SEE 5893 03:56:22,480 --> 03:56:23,960 IN MILD KNEW MOANIA, YOU SEE ON 5894 03:56:23,960 --> 03:56:25,680 TOP OF WHAT YOU SEE WITH 5895 03:56:25,680 --> 03:56:27,160 PNEUMONIA WHEN MORE SEVERE, 5896 03:56:27,160 --> 03:56:28,640 THERE IS IN ADDITION TO THAT 5897 03:56:28,640 --> 03:56:35,080 EFFECTS OF HYPOXIA AND OTHER 5898 03:56:35,080 --> 03:56:43,680 MECHANISMS. 5899 03:56:43,680 --> 03:56:44,920 >> LIKE TO GIVE OTHER SPEAKERS A 5900 03:56:44,920 --> 03:56:55,480 CHANCE TO RESPOND AS WELL. THIS 5901 03:57:00,080 --> 03:57:06,040 IS WHAT I TRY TO SAY DURING MY 5902 03:57:06,040 --> 03:57:14,600 TALK. WE CAN SEE UNDER MANY 5903 03:57:14,600 --> 03:57:20,480 CONDITION, INFECTION BUT ALSO 5904 03:57:20,480 --> 03:57:22,800 (INAUDIBLE) FROM DELIRIUM, I 5905 03:57:22,800 --> 03:57:25,400 THINK WE KNOW THAT SICKNESS 5906 03:57:25,400 --> 03:57:27,080 BEHAVIOR CAN BE ASSOCIATED WITH 5907 03:57:27,080 --> 03:57:28,400 LONG TERM PSYCHOLOGICAL 5908 03:57:28,400 --> 03:57:31,360 DISORDERS. WILL IS A LOT OF 5909 03:57:31,360 --> 03:57:34,560 LITERATURE LINKING SICKNESS 5910 03:57:34,560 --> 03:57:38,000 BEHAVIOR WITH ANXIETY, 5911 03:57:38,000 --> 03:57:44,040 DEPRESSION, AND PTSD I THINK 5912 03:57:44,040 --> 03:57:48,880 THIS SHOULD BE SEPARATED FROM -- 5913 03:57:48,880 --> 03:57:56,400 FOR ME AND CHEMOTHERAPY SO WE 5914 03:57:56,400 --> 03:57:58,600 DISORDERS. THERE ARE CERTAINLY 5915 03:57:58,600 --> 03:58:06,000 THE OTHER MECHANISMS LIKE 5916 03:58:06,000 --> 03:58:12,480 DISRUPTION, ET CETERA, I THINK 5917 03:58:12,480 --> 03:58:13,840 WE SHOULD BE ABLE TO 5918 03:58:13,840 --> 03:58:15,160 DISCRIMINATE SICKNESS BEHAVIOR 5919 03:58:15,160 --> 03:58:18,000 FROM DELIRIUM. SOMETIMES WE COME 5920 03:58:18,000 --> 03:58:20,520 FROM (INAUDIBLE). I'M NOT SURE 5921 03:58:20,520 --> 03:58:22,360 THE MODEL WE ARE TESTING IN OUR 5922 03:58:22,360 --> 03:58:24,680 LAB IS A MODEL OF DELIRIUM OR 5923 03:58:24,680 --> 03:58:31,080 MODEL OF SICKNESS BEHAVIOR. 5924 03:58:31,080 --> 03:58:32,480 >> (INAUDIBLE) DELIRIUM, SHE 5925 03:58:32,480 --> 03:58:32,680 DIED. 5926 03:58:32,680 --> 03:58:35,120 >> SO I THINK THAT IN THE HUMANS 5927 03:58:35,120 --> 03:58:36,360 IT MAKES SENSE TO DISTINGUISH 5928 03:58:36,360 --> 03:58:40,160 BETWEEN THE TWO, IN MICE IT IS A 5929 03:58:40,160 --> 03:58:41,160 LOTTERY CAN YOUER BECAUSE 5930 03:58:41,160 --> 03:58:42,160 SICKNESS BEHAVIOR STARTS TO LOOK 5931 03:58:42,160 --> 03:58:44,040 LIKE THEY ARE NOT DOING 5932 03:58:44,040 --> 03:58:46,040 ANYTHING. IT IS HYPO ACTIVE 5933 03:58:46,040 --> 03:58:48,520 STATE WHICH IS ALSO PERHAPS 5934 03:58:48,520 --> 03:58:50,080 MANIFESTATION OF HYPO ACTIVE SO 5935 03:58:50,080 --> 03:58:51,320 WE NEED TO LOOK AT DIFFERENT 5936 03:58:51,320 --> 03:58:53,480 PHENOTYPES AND CLASSIFY, USE 5937 03:58:53,480 --> 03:58:55,760 MOLECULAR CLASSIFIERS. ONE 5938 03:58:55,760 --> 03:58:58,720 THING WE HAVE SEEN AS CCL 3 GOES 5939 03:58:58,720 --> 03:58:59,920 UP ANIMALS ARE MORE LIKELY TO 5940 03:58:59,920 --> 03:59:05,840 GET HYPO ACTIVE. SO SOME POINT, 5941 03:59:05,840 --> 03:59:06,400 EIGHT MIGHT BE A -- SICKNESS 5942 03:59:06,400 --> 03:59:09,280 BEHAVIOR MAYBE A SUB ET SIT OF 5943 03:59:09,280 --> 03:59:10,480 DELIRIUM, WE HAVE TO 5944 03:59:10,480 --> 03:59:13,120 INTENTIONALLY MODEL HYPO ACTIVE 5945 03:59:13,120 --> 03:59:14,080 DELIRIUM LIKE STATE BECAUSE IT 5946 03:59:14,080 --> 03:59:17,120 IS HARD TO CONVINCE REVIEWERS 5947 03:59:17,120 --> 03:59:18,480 ABSENCE OF SOMETHING IS 5948 03:59:18,480 --> 03:59:20,200 SOMETHING. WHAT YOU JUST SAID 5949 03:59:20,200 --> 03:59:27,040 SICKNESS BEHAVIOR BUT I THINK 5950 03:59:27,040 --> 03:59:31,800 THE NEXT STAGE OF THIS WILL 5951 03:59:31,800 --> 03:59:35,480 INVOLVE CONSIDERING HYPO AND 5952 03:59:35,480 --> 03:59:37,560 HYPERACTIVE CONTINUUM OF INJURY 5953 03:59:37,560 --> 03:59:41,440 AIDED BY MOLECULAR CLASSIFIERS 5954 03:59:41,440 --> 03:59:43,080 OR EVEN BRAIN STRUCTURAL 5955 03:59:43,080 --> 03:59:46,760 SUBSTRATES LIKE CC 3. I THINK 5956 03:59:46,760 --> 03:59:48,400 SICKNESS BEHAVIOR IS A FORM OF 5957 03:59:48,400 --> 03:59:50,840 DELIRIUM IN ANIMALS. OR CAN BE 5958 03:59:50,840 --> 03:59:54,200 I SHOULD SAY. BUT IT IS ON THE 5959 03:59:54,200 --> 03:59:57,360 EXTREME END WHEN WE TAKE THOSE 5960 03:59:57,360 --> 03:59:59,920 ANIMALS AND GIVE ANTI-IL OF THEY 5961 03:59:59,920 --> 04:00:05,200 BECOME APPEAR MORE HYPERACTIVE. 5962 04:00:05,200 --> 04:00:06,520 HYPERACTIVE PHENOTYPES. SO IT 5963 04:00:06,520 --> 04:00:09,320 APPEARS THAT THIS IS ON A 5964 04:00:09,320 --> 04:00:12,000 CONTINUUM AT LEAST IN THE WORK 5965 04:00:12,000 --> 04:00:15,200 BUT IT IS HARD TO DEVELOP A 5966 04:00:15,200 --> 04:00:17,520 MODEL AND NEW FIELD AND SAY THE 5967 04:00:17,520 --> 04:00:19,680 LACK OF SOMETHING IS SOMETHING, 5968 04:00:19,680 --> 04:00:21,440 LACK OF BEHAVIOR SOMETHING BUT 5969 04:00:21,440 --> 04:00:22,440 THAT IS SOMETHING THAT WE ARE 5970 04:00:22,440 --> 04:00:24,760 SEEING. 5971 04:00:24,760 --> 04:00:28,160 >> LOOKS LIKE JACK IS ASK YOU TO 5972 04:00:28,160 --> 04:00:34,200 ANSWER THE SAME QUESTION. 5973 04:00:34,200 --> 04:00:37,800 >> WILL IS A ROLE FOR THE WORD 5974 04:00:37,800 --> 04:00:40,040 ECOLOGICAL WAS USED IN TALKS 5975 04:00:40,040 --> 04:00:43,280 THIS MORNING, FOR TASKS THAT 5976 04:00:43,280 --> 04:00:44,560 REFLECT SOMETHING IMPORTANT TO 5977 04:00:44,560 --> 04:00:49,280 NATURAL BEHAVIOR AND WHETHER 5978 04:00:49,280 --> 04:00:51,200 MENTION A FEW SPECIFICALLY LIKE 5979 04:00:51,200 --> 04:00:54,840 NEST BUILDING TASKS, THAT YOU 5980 04:00:54,840 --> 04:00:59,800 USE OR JULIE USES. OR OTHER MORE 5981 04:00:59,800 --> 04:01:03,600 COMPLEX TASKS LIKE PUZZLE BOX 5982 04:01:03,600 --> 04:01:04,920 AND EXECUTIVE FUNCTION ORIENTED 5983 04:01:04,920 --> 04:01:08,160 TASKS ARE REALLY IMPORTANT. IT 5984 04:01:08,160 --> 04:01:09,760 IS FRUSTRATING BECAUSE WE NEVER 5985 04:01:09,760 --> 04:01:12,200 LOOK AT HISTOLOGY AND SAY YES, 5986 04:01:12,200 --> 04:01:14,040 THERE IS NEURONAL DEATH OR 5987 04:01:14,040 --> 04:01:17,040 MICROGLIAL ACTIVATION IN ONE 5988 04:01:17,040 --> 04:01:20,520 SPECIFIC REASON THAT WENT TO 5989 04:01:20,520 --> 04:01:24,000 THAT BUT MODELING HETEROGENEITY 5990 04:01:24,000 --> 04:01:26,680 AND MODELING CLOTS TORE PATIENT 5991 04:01:26,680 --> 04:01:30,360 CENTERED OUTCOMES, THOSE ARE 5992 04:01:30,360 --> 04:01:33,760 CLOSER TO PATIENT CENTERED 5993 04:01:33,760 --> 04:01:35,320 OUTCOMES ARE NICE OUTCOMES. 5994 04:01:35,320 --> 04:01:36,920 >> QUESTION, RESEARCHER AT THE 5995 04:01:36,920 --> 04:01:38,880 UNIVERSITY OF VIRGINIA WHO HAS 5996 04:01:38,880 --> 04:01:40,000 DONE THIS REALLY WELL WHO IS 5997 04:01:40,000 --> 04:01:42,040 INTEGRATED A LOT OF FACTORS INTO 5998 04:01:42,040 --> 04:01:43,480 A MODEL, A MOUSE MODEL, THAT ONE 5999 04:01:43,480 --> 04:01:45,520 OF THE BENEFITS OF BEING BASIC 6000 04:01:45,520 --> 04:01:46,360 TRANSLATIONAL SCIENTIST IS WE 6001 04:01:46,360 --> 04:01:49,160 CAN DO A LOT OF CONTROLLING. BUT 6002 04:01:49,160 --> 04:01:51,600 THE QUESTION THAT BEGS THE 6003 04:01:51,600 --> 04:01:52,640 QUESTION HOW DO WE MANAGE 6004 04:01:52,640 --> 04:01:56,480 CONTROLLING FOR FACTORS OR HOW 6005 04:01:56,480 --> 04:02:03,240 DO WE INVESTIGATE INTRINSIC 6006 04:02:03,240 --> 04:02:04,680 HETEROGENEITY OF A MOUSE MODEL 6007 04:02:04,680 --> 04:02:07,120 TO UNDERSTAND THE PATHWAYS THAT 6008 04:02:07,120 --> 04:02:10,400 ARE RESPONSIBLE FOR LONG TERM 6009 04:02:10,400 --> 04:02:11,680 CONSEQUENCES OF THESE DISEASES. 6010 04:02:11,680 --> 04:02:13,480 HOW MUCH THOUGHT PUT INTO 6011 04:02:13,480 --> 04:02:15,120 MECHANICALLY VENTILATING ANIMAL 6012 04:02:15,120 --> 04:02:18,920 VERSUS JUST GIVING LPS VERSUS 6013 04:02:18,920 --> 04:02:21,880 SOME CONTINUUM ADDING NOISE TO 6014 04:02:21,880 --> 04:02:23,160 EQUATION AS (INAUDIBLE) HAS DONE 6015 04:02:23,160 --> 04:02:26,480 KEEPING ANIMALS AWAKE AND 6016 04:02:26,480 --> 04:02:28,360 CHANGING CIRCADIAN RHYTHMS AND 6017 04:02:28,360 --> 04:02:30,080 MANAGING THESE COMPLEXITIES IN A 6018 04:02:30,080 --> 04:02:32,800 MODEL WHERE WE DO HAVE CONTROL. 6019 04:02:32,800 --> 04:02:34,280 >> TO REALLY LEARN SOMETHING WE 6020 04:02:34,280 --> 04:02:35,640 HAVE TO CHANGE ONE VARIABLE AT A 6021 04:02:35,640 --> 04:02:37,040 TIME. BUT THAT DOESN'T MEAN WE 6022 04:02:37,040 --> 04:02:40,440 CAN'T STUDY HETEROGENEITY, WE 6023 04:02:40,440 --> 04:02:43,280 HAVE TO UNDERSTAND WHAT FACTORS 6024 04:02:43,280 --> 04:02:43,880 CONTRIBUTE TO DIFFERENT 6025 04:02:43,880 --> 04:02:46,480 OUTCOMES. ONE POINT DISCUSSED 6026 04:02:46,480 --> 04:02:51,600 THAT I WANTED TO CLARIFY, THE 6027 04:02:51,600 --> 04:02:53,520 ACUTE NEUROLOGICAL SYNDROME IS 6028 04:02:53,520 --> 04:02:55,080 DISTINCT FROM CHRONIC 6029 04:02:55,080 --> 04:02:56,320 NEUROLOGICAL SYNDROME, THEY 6030 04:02:56,320 --> 04:02:58,280 MAYBE RELATED IN IMPORTANT WAYS 6031 04:02:58,280 --> 04:02:59,360 ONE MAY PREDICT THE OTHER BUT 6032 04:02:59,360 --> 04:03:00,360 MIGHT NOT SO IT IS IMPORTANT TO 6033 04:03:00,360 --> 04:03:06,400 THINK ABOUT ACUTE NEUROLOGICAL 6034 04:03:06,400 --> 04:03:08,560 DYSFUNCTION VERSUS CHRONIC. KIND 6035 04:03:08,560 --> 04:03:12,440 OF LIKE I CAN LONG HE WERE 6036 04:03:12,440 --> 04:03:13,560 DEVELOPMENT VERSUS T-CELL 6037 04:03:13,560 --> 04:03:15,880 THERAPY, MAYBE RELATED BUT ALSO 6038 04:03:15,880 --> 04:03:17,320 DISTINCT. THE TIME COURSE AFTER 6039 04:03:17,320 --> 04:03:20,880 THE INSULT LOOKING HOW A 6040 04:03:20,880 --> 04:03:22,520 PARTICULAR RESPIRATORY INFECTION 6041 04:03:22,520 --> 04:03:24,320 MAY INFLUENCE THE LONG TERM 6042 04:03:24,320 --> 04:03:26,120 OUTCOME IN MICE THAT HAD 6043 04:03:26,120 --> 04:03:30,000 DIFFERENT EARLY LIFE EXPERIENCE 6044 04:03:30,000 --> 04:03:32,240 UNDERSTAND OR DIFFERENT 6045 04:03:32,240 --> 04:03:33,480 CONCOMITANT EXPERIENCE BUT 6046 04:03:33,480 --> 04:03:34,360 VARYING ONLY ONE THING. THIS IS 6047 04:03:34,360 --> 04:03:35,840 THE SECOND TIME YOU GET 6048 04:03:35,840 --> 04:03:41,240 PNEUMONIA CHANGE THE WAY YOUR 6049 04:03:41,240 --> 04:03:42,480 BRAIN RESPONDS TO VARIOUS WAYS 6050 04:03:42,480 --> 04:03:45,240 TO THIS CHALLENGE. DOES SLEEP 6051 04:03:45,240 --> 04:03:47,160 DEPRIVATION INFLUENCE THAT, 6052 04:03:47,160 --> 04:03:48,480 CONCOMITANT MEDICATION INFLUENCE 6053 04:03:48,480 --> 04:03:50,720 IT BUT ONLY TEST ONE THING AT A 6054 04:03:50,720 --> 04:03:52,320 TIME SO YOU HAVE TO BE COG 6055 04:03:52,320 --> 04:03:53,280 COGNIZANT OF JUST THAT 6056 04:03:53,280 --> 04:03:57,720 PRINCIPLE. THIS IS ARE 6057 04:03:57,720 --> 04:03:58,240 IMPORTANT VARIABLES TO 6058 04:03:58,240 --> 04:04:04,960 UNDERSTAND. 6059 04:04:04,960 --> 04:04:05,120 >> 6060 04:04:05,120 --> 04:04:07,960 >> A FIZZ YOU LOGICALLY MORE 6061 04:04:07,960 --> 04:04:09,080 INTEGRATED PRE-TRANSLATIONAL 6062 04:04:09,080 --> 04:04:10,720 MODELS ARE REALLY IMPORTANT FOR 6063 04:04:10,720 --> 04:04:15,440 PROVIDING INSIGHT. I THINK WE 6064 04:04:15,440 --> 04:04:18,040 NEED MORE COMPREHENSIVELY 6065 04:04:18,040 --> 04:04:19,440 INTEGRATED PHYSIOLOGICAL 6066 04:04:19,440 --> 04:04:21,040 MEASUREMENTS TO GO WITH WHAT WE 6067 04:04:21,040 --> 04:04:23,200 NORMALLY HAVE AS OUTCOMES IN 6068 04:04:23,200 --> 04:04:26,400 THESE PRE-CLINICAL MODELS. THAT 6069 04:04:26,400 --> 04:04:29,320 WILL HELP A LOT AND MATCH 6070 04:04:29,320 --> 04:04:35,480 CLINICAL SCENARIO BETTER. 6071 04:04:35,480 --> 04:04:36,680 >> I WAS GOING TO SAY, I THINK 6072 04:04:36,680 --> 04:04:38,360 WE HAVE TO MEASURE ONE VARIABLE 6073 04:04:38,360 --> 04:04:41,120 AT A TIME BUT TO OVERCOME THE 6074 04:04:41,120 --> 04:04:43,280 HETEROGENEITY OF A CLINICAL 6075 04:04:43,280 --> 04:04:45,160 POPULATION TO AID TRANSLATION WE 6076 04:04:45,160 --> 04:04:47,320 HAVE TO LOOK FOR BIG TREATMENT 6077 04:04:47,320 --> 04:04:48,640 EFFECTS. NOT SMALL TREATMENT 6078 04:04:48,640 --> 04:04:50,480 EFFECTS ON ISOLATED VARIABLES 6079 04:04:50,480 --> 04:04:53,400 AND THAT MAYBE WITH STANDS 6080 04:04:53,400 --> 04:04:54,280 HETEROGENEITY OF THE CLINICAL 6081 04:04:54,280 --> 04:04:58,640 POPULATION. I AGREE WITH 6082 04:04:58,640 --> 04:05:01,080 MICHELLE THAT THE ACUTE AND 6083 04:05:01,080 --> 04:05:02,160 CHRONIC ARE VERY DIFFERENT IN 6084 04:05:02,160 --> 04:05:04,000 OUR MODELS WHEN WE LOOK AT A 6085 04:05:04,000 --> 04:05:06,480 DIFFERENT TIME LINE, IF WE 6086 04:05:06,480 --> 04:05:08,760 ADMINISTER INFLAMMATORY 6087 04:05:08,760 --> 04:05:11,840 MODULATION AT DELAYED TIME POINT 6088 04:05:11,840 --> 04:05:14,160 THE TREATMENT EFFECT IS LOWER. 6089 04:05:14,160 --> 04:05:16,080 THAT'S PROBABLY BECAUSE THERE IS 6090 04:05:16,080 --> 04:05:17,520 ALREADY BRAIN IS ON FIRE SO TO 6091 04:05:17,520 --> 04:05:19,080 SPEAK, THERE IS MICROGLIAL 6092 04:05:19,080 --> 04:05:20,600 ACTIVATION, ALL THE OTHER THING 6093 04:05:20,600 --> 04:05:21,960 WE TALKED ABOUT. 6094 04:05:21,960 --> 04:05:24,200 >> THERE IS AN OPPORTUNITY HERE 6095 04:05:24,200 --> 04:05:28,280 TO MATCH PRE-CLINICAL STUDIES 6096 04:05:28,280 --> 04:05:31,480 TOGETHER WITH COHORT OF PATIENTS 6097 04:05:31,480 --> 04:05:33,280 SIDE BY SIDE. AND CONTROL 6098 04:05:33,280 --> 04:05:34,920 VARIABLES IN A WAY IN BOTH 6099 04:05:34,920 --> 04:05:38,880 POPULATIONS TO SEE HOW CLOSELY 6100 04:05:38,880 --> 04:05:40,320 THEY RELATE. I THINK THERE'S 6101 04:05:40,320 --> 04:05:41,600 REAL OPPORTUNITY THERE. 6102 04:05:41,600 --> 04:05:43,520 >> I THINK THAT ANYTHING WE FIND 6103 04:05:43,520 --> 04:05:46,360 IN MICE WE HAVE TO SEEK THE 6104 04:05:46,360 --> 04:05:47,600 GROUND TRUTH IN OUR PATIENTS AND 6105 04:05:47,600 --> 04:05:49,080 SEE THAT IT IS REALLY HAPPENING 6106 04:05:49,080 --> 04:05:50,400 AND WE HAVE TO TAKE VARIABLES IN 6107 04:05:50,400 --> 04:05:51,800 OUR PATIENTS THAT CORRELATE WITH 6108 04:05:51,800 --> 04:05:55,160 THE OUTCOME AND TEST THEIR 6109 04:05:55,160 --> 04:05:57,040 MECHANISM IN MICE. THE MICE ARE 6110 04:05:57,040 --> 04:05:59,680 ONLY A MEANS TO THE END. TO HELP 6111 04:05:59,680 --> 04:06:02,520 OUR PATIENTS SO P IT IS NOT 6112 04:06:02,520 --> 04:06:03,560 HAPPENING WITH PATIENT, WHAT 6113 04:06:03,560 --> 04:06:06,080 HAPPENS IN OUR MICE DOESN'T 6114 04:06:06,080 --> 04:06:07,480 MATTER. 6115 04:06:07,480 --> 04:06:10,320 >> YOU HAVE A PROBLEM WITH 6116 04:06:10,320 --> 04:06:11,120 HETEROGENEITY IF YOU WANT TO 6117 04:06:11,120 --> 04:06:15,440 ADDRESS THE HETEROGENEITY YOU 6118 04:06:15,440 --> 04:06:17,360 NEED A LOT OF MICE. I DON'T KNOW 6119 04:06:17,360 --> 04:06:20,720 HOW IT IS IN THE UNITED STATES 6120 04:06:20,720 --> 04:06:23,120 BUT IN FRANCE YOU HAVE TO HAVE 6121 04:06:23,120 --> 04:06:23,800 (INAUDIBLE) EVERYWHERE AND YOU 6122 04:06:23,800 --> 04:06:31,240 CANNOT -- NO. IN ORDER TO 6123 04:06:31,240 --> 04:06:34,880 EVALUATE HETEROGENEITY. 6124 04:06:34,880 --> 04:06:35,360 SPEAKER5: (OVERLAPPING 6125 04:06:35,360 --> 04:06:35,640 SPEAKERS). 6126 04:06:35,640 --> 04:06:36,200 >> IT IS MORE DIFFICULT FOR 6127 04:06:36,200 --> 04:06:40,760 SURE. CERTAINLY COMMITTEES BUT 6128 04:06:40,760 --> 04:06:42,320 EASIER TO DO SMALL ANIMAL 6129 04:06:42,320 --> 04:06:45,120 EXPERIMENTS IN THE US. ONE 6130 04:06:45,120 --> 04:06:47,320 THING I THINK POWERFUL MODEL I 6131 04:06:47,320 --> 04:06:48,960 HAVE SEEN INCREASINGLY IN 6132 04:06:48,960 --> 04:06:50,440 NEUROSCIENCE BEING USED 6133 04:06:50,440 --> 04:06:53,200 ROCKEFELLAR IS DOING THIS REALLY 6134 04:06:53,200 --> 04:06:56,200 BRILLIANT NEUROSCIENTIST THERE, 6135 04:06:56,200 --> 04:06:58,160 TO USE I FORGET HOW SHE -- 6136 04:06:58,160 --> 04:06:59,560 BASICALLY THEY ARE GETTING MICE 6137 04:06:59,560 --> 04:07:01,760 AND RATS FROM THE SUBWAY, 6138 04:07:01,760 --> 04:07:02,600 GETTING NATURAL ENVIRONMENT RATS 6139 04:07:02,600 --> 04:07:05,680 THAT ARE HETEROGENOUS. OUR LAB 6140 04:07:05,680 --> 04:07:08,040 MICE AND RATS ARE GENETICALLY 6141 04:07:08,040 --> 04:07:11,880 IDENTICAL WITHIN A STRAIN. AND 6142 04:07:11,880 --> 04:07:13,680 SO THEY BECOME VERY, VERY, VERY 6143 04:07:13,680 --> 04:07:15,200 SIMILAR AN IT IS HARD TO SEE 6144 04:07:15,200 --> 04:07:17,000 HETEROGENEITY BUT IF YOU JUST 6145 04:07:17,000 --> 04:07:19,880 GET HETEROGENOUS POPULATION OF 6146 04:07:19,880 --> 04:07:20,640 NATURALISTIC MICE YOU 6147 04:07:20,640 --> 04:07:22,880 AUTOMATICALLY HAVE MORE GENETIC 6148 04:07:22,880 --> 04:07:25,160 VARIABILITY DIFFERENCES IN LIFE 6149 04:07:25,160 --> 04:07:27,440 EXPERIENCE, EXPOSURES. AND THE 6150 04:07:27,440 --> 04:07:30,880 RESULTS ARE NOT NEARLY AS CLEAN 6151 04:07:30,880 --> 04:07:32,200 BUT YOU CAN LEARN INTERESTING 6152 04:07:32,200 --> 04:07:35,040 THINGS ABOUT SUBPOPULATIONS THAT 6153 04:07:35,040 --> 04:07:35,760 HAVE DIFFERENT RESPONSES SO 6154 04:07:35,760 --> 04:07:37,840 ANOTHER WAY TO STAY WITHIN SMALL 6155 04:07:37,840 --> 04:07:40,160 ANIMAL BUS BETTER MODEL THE 6156 04:07:40,160 --> 04:07:40,920 HETEROGENEITY AND LIFE 6157 04:07:40,920 --> 04:07:46,240 EXPERIENCE THAT PEOPLE HAVE. 6158 04:07:46,240 --> 04:07:47,720 >> THERE HAVE BEEN GREAT POINTS 6159 04:07:47,720 --> 04:07:50,520 BROUGHT UP IN CHAT AS AS WELL, 6160 04:07:50,520 --> 04:07:52,480 TIM BROUGHT UP LARGE PANEL 6161 04:07:52,480 --> 04:07:54,560 STUDIES VALUE EXPANDING WHICH 6162 04:07:54,560 --> 04:07:55,720 MAYBE DIFFICULT TO IMAGINE IN 6163 04:07:55,720 --> 04:07:58,440 EUROPE BUT U.S. IT IS CERTAINLY 6164 04:07:58,440 --> 04:08:00,840 FEASIBLE AND JULIE FROM 6165 04:08:00,840 --> 04:08:02,000 VANDERBILT BROUGHT UP THE NEED 6166 04:08:02,000 --> 04:08:03,760 FOR CLINICAL TRIALS THAT INCLUDE 6167 04:08:03,760 --> 04:08:05,280 BIOSPECIMENS THAT WE CAN 6168 04:08:05,280 --> 04:08:06,800 LEVERAGE TO APPLY TO OUR 6169 04:08:06,800 --> 04:08:07,920 PRE-CLINICAL AND TRANSLATIONAL 6170 04:08:07,920 --> 04:08:12,280 MODELS. 6171 04:08:12,280 --> 04:08:14,200 >> ALONG THOSE LINES I WANT TO 6172 04:08:14,200 --> 04:08:17,360 TURN TO THE PANEL AND AS WELL AS 6173 04:08:17,360 --> 04:08:20,440 THE CHAT THE QUESTION THAT JACK 6174 04:08:20,440 --> 04:08:22,440 ASKED EARLIER TURN ON ITS HEAD. 6175 04:08:22,440 --> 04:08:24,000 IF WE HAVE TOOLS TO STUDY 6176 04:08:24,000 --> 04:08:30,320 MECHANISM OF INJURY, MANY OR ALL 6177 04:08:30,320 --> 04:08:32,960 OF YOU INCORPORATE SOME CLINICAL 6178 04:08:32,960 --> 04:08:35,200 SPECIMENS OR BIOMARKERS INTO 6179 04:08:35,200 --> 04:08:36,680 ANIMAL STUDIES THAT YOU 6180 04:08:36,680 --> 04:08:39,000 DESCRIBED BUT IF THERE IS 6181 04:08:39,000 --> 04:08:41,000 SOMETHING FROM THE CLINICAL 6182 04:08:41,000 --> 04:08:46,080 TRANSLATIONAL WORLD WE CAN USE 6183 04:08:46,080 --> 04:08:48,320 TO HELP WITH REVERSE TRANSLATION 6184 04:08:48,320 --> 04:08:50,760 OR INCREASING RELEVANCE OF THE 6185 04:08:50,760 --> 04:08:52,400 ANIMAL STUDIES WE DO WHAT WOULD 6186 04:08:52,400 --> 04:08:57,000 THAT BE? 6187 04:08:57,000 --> 04:09:00,320 >> TIGHTLY CONTROLLED TIME LINES 6188 04:09:00,320 --> 04:09:02,160 REALLY VALUABLE THROUGH CLINICAL 6189 04:09:02,160 --> 04:09:03,960 COURSE AND GETTING UNDERSTANDING 6190 04:09:03,960 --> 04:09:06,200 OF NATURAL HISTORY OF INFECTION 6191 04:09:06,200 --> 04:09:09,440 RECOVERY IS REALLY IMPORTANT. 6192 04:09:09,440 --> 04:09:13,120 FEASIBLE TO DO ONE TIME POINT 6193 04:09:13,120 --> 04:09:16,800 BUT HAVING TEMPORAL SENSITIVITY 6194 04:09:16,800 --> 04:09:18,240 IS VALUABLE AND SOMETHING MATCH 6195 04:09:18,240 --> 04:09:23,080 PRE-CLINICAL MODELS. 6196 04:09:23,080 --> 04:09:25,280 >> I THINK ONE QUESTION IS WHAT 6197 04:09:25,280 --> 04:09:28,960 DO WE WANT TO STUDY, THE INSULT 6198 04:09:28,960 --> 04:09:30,520 PROCESS? WHAT IS HAPPEN IN THE 6199 04:09:30,520 --> 04:09:34,640 ACTIVE PHASE THAT CAN EXPANDS 6200 04:09:34,640 --> 04:09:36,040 WHAT WE HAVE AFTER? DO WE WANTS 6201 04:09:36,040 --> 04:09:42,440 TO ADDRESS THE RECOVERY PROCESS? 6202 04:09:42,440 --> 04:09:46,520 THIS IS IMPORTANT. IF WE WANT TO 6203 04:09:46,520 --> 04:09:48,200 ADDRESS MECHANISMS THAT 6204 04:09:48,200 --> 04:09:49,600 (INAUDIBLE) LONG TERM 6205 04:09:49,600 --> 04:09:52,200 PSYCHOLOGICAL OR CONNECTIVE 6206 04:09:52,200 --> 04:09:54,040 DISORDER WE HAVE LONG TERM 6207 04:09:54,040 --> 04:09:56,400 RECOVERY PROCESS AND SO 6208 04:09:56,400 --> 04:09:58,320 PLASTICITY, ET CETERA SO MAYBE 6209 04:09:58,320 --> 04:10:02,320 SOME TIME LINE. SO I THINK THAT 6210 04:10:02,320 --> 04:10:04,720 IS TWO QUESTIONS WHAT ARE 6211 04:10:04,720 --> 04:10:07,920 MECHANISMS OF ACUTE INJURY OF 6212 04:10:07,920 --> 04:10:10,960 BRAIN CELLS AND HOW CAN EXPLAIN 6213 04:10:10,960 --> 04:10:13,640 LONG TERM SEQUELAE BUT ALSO THE 6214 04:10:13,640 --> 04:10:17,960 OTHER QUESTION IS HOW WE CAN 6215 04:10:17,960 --> 04:10:21,400 ASSESS AND ADDRESS MECHANISMS OF 6216 04:10:21,400 --> 04:10:23,240 RECOVERY PROCESS. I DON'T THINK 6217 04:10:23,240 --> 04:10:24,960 THERE ARE MANY STUDIED. SO IT IS 6218 04:10:24,960 --> 04:10:27,440 NOT THE SAME TIME, WE ARE NOT ON 6219 04:10:27,440 --> 04:10:30,080 THE SAME TIME LINE. BUT I DON'T 6220 04:10:30,080 --> 04:10:31,080 KNOW IF I'M CLEAR WHAT I'M 6221 04:10:31,080 --> 04:10:37,200 SAYING. AS MICHELLE SAID, WE 6222 04:10:37,200 --> 04:10:39,600 CANNOT MIX ACTIONS AND MAYBE THE 6223 04:10:39,600 --> 04:10:40,920 CHRONIC PHASE. IF WE WANT TO 6224 04:10:40,920 --> 04:10:42,480 LOOK AT CHRONIC PHASE MAYBE WE 6225 04:10:42,480 --> 04:10:45,600 HAVE TO LOOK AT MECHANISMS OF 6226 04:10:45,600 --> 04:10:50,720 RECOVERY AND HOW CAN -- WE CAN 6227 04:10:50,720 --> 04:10:53,560 STIMULATE RECOVERY PLASTICITY. 6228 04:10:53,560 --> 04:10:55,400 >> I THINK THERE IS A PARADIGM 6229 04:10:55,400 --> 04:10:57,120 IN NEUROSCIENCE THAT THERE IS -- 6230 04:10:57,120 --> 04:10:59,280 YOU CAN EITHER AFFECT ACUTE 6231 04:10:59,280 --> 04:11:01,960 INSULTS AND IMPROVE OUTCOMES BY 6232 04:11:01,960 --> 04:11:03,280 AFFECTING WITHIN THE FIRST 30 6233 04:11:03,280 --> 04:11:05,480 MINUTES OR 60 MINUTES OF STROKE 6234 04:11:05,480 --> 04:11:08,840 VERSUS TRYING TO FIND WAYS TO RE 6235 04:11:08,840 --> 04:11:10,920 RECOVER. NEURORESTORETIVE 6236 04:11:10,920 --> 04:11:12,760 THERAPIES. IN THIS FIELD IN 6237 04:11:12,760 --> 04:11:15,160 PARTICULAR OFTEN I FEEL AS BASIC 6238 04:11:15,160 --> 04:11:17,320 SCIENTIST OFTEN DAMAGE IS DONE 6239 04:11:17,320 --> 04:11:19,160 PATIENT COMES TO HOSPITAL AND 6240 04:11:19,160 --> 04:11:21,320 CERTAINLY THAT CAN BE LEVERAGED 6241 04:11:21,320 --> 04:11:23,000 BY CHANGING DELIRIUM OR 6242 04:11:23,000 --> 04:11:25,000 AFFECTING ACUTE INFLAMMATION THE 6243 04:11:25,000 --> 04:11:26,120 FIRST SEVERAL DAYS OF 6244 04:11:26,120 --> 04:11:27,680 HOSPITALIZATION WITH POTENTIAL 6245 04:11:27,680 --> 04:11:29,040 NEGATIVE EFFECTIVE WORSENING 6246 04:11:29,040 --> 04:11:30,200 OUTCOMES WHICH I THINK IS OUR 6247 04:11:30,200 --> 04:11:32,520 BIGGEST FEAR. BUT MICHELLE, I 6248 04:11:32,520 --> 04:11:33,480 THINK YOU HAVE SOMETHING TO ADD 6249 04:11:33,480 --> 04:11:35,800 >> YEAH. I WOULD JUST POINT OUT 6250 04:11:35,800 --> 04:11:39,120 THAT A LOT OF WHAT MAYBE GOING 6251 04:11:39,120 --> 04:11:46,160 ON NEURO BIOLOGICALLY IS 6252 04:11:46,160 --> 04:11:47,280 DISCRIMINATION RATHER THAN 6253 04:11:47,280 --> 04:11:49,640 DESTRUCTION. WE DON'T SEE CELL 6254 04:11:49,640 --> 04:11:52,560 DEATH OF IRREPLACEABLE CELLS WE 6255 04:11:52,560 --> 04:11:54,200 SEE DISREGULATION OF PLASTICITY, 6256 04:11:54,200 --> 04:11:56,200 WE SEE DISREGULATION OF 6257 04:11:56,200 --> 04:11:57,880 COMMUNICATION. AND THAT CAN AT 6258 04:11:57,880 --> 04:12:01,560 LEAST IN PRE-CLINICAL MODELS 6259 04:12:01,560 --> 04:12:03,840 WITH MILD DISEASE, AGAIN THERE 6260 04:12:03,840 --> 04:12:05,000 ARE THINGS LIKE STROKE THAT 6261 04:12:05,000 --> 04:12:08,440 CAN'T BE REGENERATED BUT JUST 6262 04:12:08,440 --> 04:12:09,600 INFLAMMATION INDUCE 6263 04:12:09,600 --> 04:12:11,120 DISREGULATION CAN BE RESTORED 6264 04:12:11,120 --> 04:12:12,640 EXPERIMENTALLY SO THAT GIVES ME 6265 04:12:12,640 --> 04:12:15,240 HOPE THAT WE CAN FIND WAYS TO 6266 04:12:15,240 --> 04:12:16,920 MOLECULARLY COACH THESE CELLS 6267 04:12:16,920 --> 04:12:19,720 BACK TO HOMEOSTATIC AND PLASTIC 6268 04:12:19,720 --> 04:12:21,040 STATE IN A WAY TO IMPROVE 6269 04:12:21,040 --> 04:12:26,080 COGNITION AND IMPROVE COGNITIVE 6270 04:12:26,080 --> 04:12:28,760 ENERGY THROUGHOUT THE DAY. AND 6271 04:12:28,760 --> 04:12:33,040 REALLY HELP QUALITY OF LIFE. I'M 6272 04:12:33,040 --> 04:12:35,000 ENCOURAGED BY SYMPTOMATIC 6273 04:12:35,000 --> 04:12:36,640 TREATMENTS IN CANCER RELATED 6274 04:12:36,640 --> 04:12:38,400 COGNITIVE SPACE, ONE OF MY 6275 04:12:38,400 --> 04:12:40,360 CLINICAL SPECIALTIES WHERE 6276 04:12:40,360 --> 04:12:42,200 PEOPLE YEARS AFTER VERY 6277 04:12:42,200 --> 04:12:43,880 NEUROTOXIC THERAPIES LIKE 6278 04:12:43,880 --> 04:12:45,800 CRANIAL RADIATION CAN DO BETTER 6279 04:12:45,800 --> 04:12:48,320 WITH SIMILAR SYMPTOMATIC 6280 04:12:48,320 --> 04:12:49,720 MANAGEMENT WITH METHYLPHENIDATE 6281 04:12:49,720 --> 04:12:51,160 AND OTHER THINGS TO HELP GET 6282 04:12:51,160 --> 04:12:52,960 THEM THROUGH THEIR DAY. IN A WAY 6283 04:12:52,960 --> 04:12:54,160 THAT MAKES MY REALLY BELIEVE 6284 04:12:54,160 --> 04:12:57,160 THAT IF WE COULD REGENERATE OR 6285 04:12:57,160 --> 04:13:00,920 RESTORE HOMEOSTASIS, CELLULARLY, 6286 04:13:00,920 --> 04:13:03,440 PERHAPS ADDRESS NEURAL 6287 04:13:03,440 --> 04:13:04,400 INFLAMMATION, ENCOURAGE 6288 04:13:04,400 --> 04:13:06,200 MECHANISMS OF PLASTICITY, 6289 04:13:06,200 --> 04:13:08,240 REPLACE MECHANISMS OF 6290 04:13:08,240 --> 04:13:09,840 PLASTICITY, WE CAN MAKE PEOPLE 6291 04:13:09,840 --> 04:13:10,600 BETTER. SO SOME OF THE 6292 04:13:10,600 --> 04:13:12,160 CHALLENGES WE THINK ABOUT 6293 04:13:12,160 --> 04:13:12,920 REGENERATION AFTER STROKE THAT 6294 04:13:12,920 --> 04:13:15,760 IS A HUGE CHALLENGE, TO REGROW 6295 04:13:15,760 --> 04:13:17,240 THE HOLE IN THE BRAIN, THAT IS 6296 04:13:17,240 --> 04:13:18,480 NOT THE SITUATION WE HAVE HERE. 6297 04:13:18,480 --> 04:13:19,880 WE HAVE A MUCH EASIER SITUATION 6298 04:13:19,880 --> 04:13:21,360 BUT WE HAVE TO UNDERSTAND THE 6299 04:13:21,360 --> 04:13:22,640 MECHANISMS IN ENOUGH DETAIL TO 6300 04:13:22,640 --> 04:13:23,800 TARGET THEM. 6301 04:13:23,800 --> 04:13:29,200 >> I FULLY AGREE. WE THE SAME 6302 04:13:29,200 --> 04:13:34,400 TYPE AS BRAIN CHRONICITY 6303 04:13:34,400 --> 04:13:36,520 MATTERS. IN OUR MODEL THE CC 3 6304 04:13:36,520 --> 04:13:39,400 EXPRESSION EARLY APOPTOTIC 6305 04:13:39,400 --> 04:13:41,400 MARKER ACTUALLY IT REVERSES IF 6306 04:13:41,400 --> 04:13:43,240 THE INSULT IS TAKEN AWAY. SO 6307 04:13:43,240 --> 04:13:48,760 WHEN WE LOOK AT MARKERS OF 6308 04:13:48,760 --> 04:13:49,800 INREVERSIBLE CELL DEATH WE ARE 6309 04:13:49,800 --> 04:13:51,480 NOT SEEING THAT IN ACUTE PHASE, 6310 04:13:51,480 --> 04:13:53,200 ONLY WHEN YOU LET THAT INJURY 6311 04:13:53,200 --> 04:13:54,680 PERSIST FOR A WHILE. SO WHETHER 6312 04:13:54,680 --> 04:14:00,400 THAT REFLECTS LIKE SENESCENCE OR 6313 04:14:00,400 --> 04:14:02,400 SOMETHING ELSE WHICH IS 6314 04:14:02,400 --> 04:14:03,680 REVERSIBLE AND IS STILL AN OPEN 6315 04:14:03,680 --> 04:14:05,360 QUESTION. BUT I THIS I THAT THAT 6316 04:14:05,360 --> 04:14:10,040 IS VERY ENCOURAGING. AS MICHELLE 6317 04:14:10,040 --> 04:14:10,280 SAID. 6318 04:14:10,280 --> 04:14:13,640 >> I WOULD LIKE TO MAKE ANALOGY. 6319 04:14:13,640 --> 04:14:19,920 FEW YEARS AGO WE HAVE SHOWN 6320 04:14:19,920 --> 04:14:23,120 (INAUDIBLE) MODEL MICE KNOW THAT 6321 04:14:23,120 --> 04:14:24,960 THERE IS A (INAUDIBLE) SATELLITE 6322 04:14:24,960 --> 04:14:26,560 CELLS, SATELLITE CELLS ARE 6323 04:14:26,560 --> 04:14:28,440 IMPORTANT FOR REGENERATION OF 6324 04:14:28,440 --> 04:14:29,800 MUSCLE. SO WE FOUND THAT DURING 6325 04:14:29,800 --> 04:14:32,440 THE SEPSIS, THERE IS A 6326 04:14:32,440 --> 04:14:33,840 (INAUDIBLE) OF THE SATELLITE 6327 04:14:33,840 --> 04:14:37,520 CELLS AND SO THE (INAUDIBLE) SO 6328 04:14:37,520 --> 04:14:42,520 MAYBE COULD BE A MECHANISM OF 6329 04:14:42,520 --> 04:14:44,520 CRITICAL -- TWO QUESTIONS, IS 6330 04:14:44,520 --> 04:14:47,880 THIS OCCURRENCE WHERE THE ACTIVE 6331 04:14:47,880 --> 04:14:50,000 PHRASE OF SEPSIS, THERE ARE TWO 6332 04:14:50,000 --> 04:14:54,040 QUESTIONS, IS THERE A WAY TO 6333 04:14:54,040 --> 04:14:56,120 PROTECT SATELLITE CELLS THEN 6334 04:14:56,120 --> 04:14:57,520 MUSCLE COULD REGENERATE OR IS 6335 04:14:57,520 --> 04:15:00,720 THERE A WAY AFTER THE INSULT TO 6336 04:15:00,720 --> 04:15:02,080 MAKE THE SATELLITE CELLS WORK 6337 04:15:02,080 --> 04:15:05,360 AGAIN. I THINK THAT THESE ARE 6338 04:15:05,360 --> 04:15:07,400 TWO DIFFERENCE APPROACH TRYING 6339 04:15:07,400 --> 04:15:09,280 TO PROTECT THE BRAIN FROM THE 6340 04:15:09,280 --> 04:15:10,840 ACTIVE INSULT, AFTER ACUTE 6341 04:15:10,840 --> 04:15:13,960 TRYING TO MAKE IT WORKING AGAIN 6342 04:15:13,960 --> 04:15:18,880 AS YOU SAID MICHELLE TRYING TO 6343 04:15:18,880 --> 04:15:21,000 RESTORE BRAIN FUNCTION. I THINK 6344 04:15:21,000 --> 04:15:25,640 THAT NOT THE SAME. 6345 04:15:25,640 --> 04:15:28,920 >> THERE COULD BE POTENTIAL 6346 04:15:28,920 --> 04:15:30,480 CUMULATIVE EFFECT, THE INITIAL 6347 04:15:30,480 --> 04:15:33,240 INJURY LEADS TO MORE SECONDARY 6348 04:15:33,240 --> 04:15:34,480 HITS AND PROGRESSIVE WORSENING 6349 04:15:34,480 --> 04:15:40,320 OVER TIME. THAT SOME OF THESE 6350 04:15:40,320 --> 04:15:43,920 FACTORS WE DON'T KNOW WHAT THEIR 6351 04:15:43,920 --> 04:15:48,040 HALF LIFE IS. IT MAY NOT GO 6352 04:15:48,040 --> 04:15:51,000 AWAY, MAY SET YOU UP FOR 6353 04:15:51,000 --> 04:15:52,280 WORSENING OF CONDITIONS AND 6354 04:15:52,280 --> 04:15:53,480 PROGRESSIVE WORSENING OF 6355 04:15:53,480 --> 04:15:55,040 COGNITIVE DYSFUNCTION AND THOSE 6356 04:15:55,040 --> 04:15:56,600 ARE ALL REALLY IMPORTANT 6357 04:15:56,600 --> 04:15:58,040 QUESTIONS TO ANSWER, 6358 04:15:58,040 --> 04:15:59,680 RELATIONSHIP BETWEEN INITIAL 6359 04:15:59,680 --> 04:16:00,400 DISREGULATION, VERSUS 6360 04:16:00,400 --> 04:16:03,280 PROGRESSIVE WORSENING. AND THEN 6361 04:16:03,280 --> 04:16:05,560 ALONG THOSE LINES, WE HAVEN'T 6362 04:16:05,560 --> 04:16:09,800 TALKED ABOUT A SECONDARY 6363 04:16:09,800 --> 04:16:20,360 GENOTYPE BACKGROUND APOE 4 GENE 6364 04:16:21,040 --> 04:16:22,920 NEUROCOGNITIVE INFECTION IN 6365 04:16:22,920 --> 04:16:24,520 SETTING OF INFECTION. ALL NEEDS 6366 04:16:24,520 --> 04:16:26,600 TO BE CONSIDERED AND ADDRESS. 6367 04:16:26,600 --> 04:16:29,400 THE MULTIPLICITY OF FACTORS THAT 6368 04:16:29,400 --> 04:16:31,520 INFLUENCE HETEROGENEITY HAVE TO 6369 04:16:31,520 --> 04:16:33,280 BE BROKEN DOWN AND I THINK AS 6370 04:16:33,280 --> 04:16:34,400 MICHELLE SAID YOU CAN ONLY STUDY 6371 04:16:34,400 --> 04:16:35,880 ONE THING AT A TIME. BUT THERE 6372 04:16:35,880 --> 04:16:38,760 NEEDS TO BE PROGRESSIVE 6373 04:16:38,760 --> 04:16:39,960 CONSIDERATION OF THE 6374 04:16:39,960 --> 04:16:46,720 MULTIPLICATIVE EFFECTS WE SEE. 6375 04:16:46,720 --> 04:16:48,120 >> I WANT TO BRING IN P 6376 04:16:48,120 --> 04:16:49,600 FASCINATING QUESTIONS TO THE 6377 04:16:49,600 --> 04:16:58,200 CHAT TO RECOVERY AND RESILIENCE 6378 04:16:58,200 --> 04:16:59,920 RELATING TO DYSFUNCTION VERSUS 6379 04:16:59,920 --> 04:17:04,840 DESTRUCTION. WE KNOW THAT 6380 04:17:04,840 --> 04:17:06,320 MICHELLE PRESENTED DATA ABOUT 6381 04:17:06,320 --> 04:17:08,000 ADULT NEUROGENESIS. WE KNOW 6382 04:17:08,000 --> 04:17:09,960 THINGS THAT ARE EXTRINSIC TO 6383 04:17:09,960 --> 04:17:12,200 INDIVIDUAL ANIMAL LIKE EXERCISE 6384 04:17:12,200 --> 04:17:14,680 PHYSICAL ACTIVITY CAN HAVE 6385 04:17:14,680 --> 04:17:15,320 IMPORTANT EFFECTS FOR BRAIN 6386 04:17:15,320 --> 04:17:23,600 HEALTH. AND FOR RESILIENCE -- 6387 04:17:23,600 --> 04:17:34,040 RECOVERY OR SOCIOECONOMIC 6388 04:17:44,080 --> 04:17:45,200 DEPRIVATION. DO WE THINK THOSE 6389 04:17:45,200 --> 04:17:47,080 FLAYPLAY A ROLE IN THE TYPES OF 6390 04:17:47,080 --> 04:17:47,960 PROCESSING THAT YOU HAVE BEEN 6391 04:17:47,960 --> 04:17:49,680 DECEMBER KISSING HERE? THE -- 6392 04:17:49,680 --> 04:17:50,720 DISCUSSING HERE IN THE ANIMAL 6393 04:17:50,720 --> 04:17:53,760 MODELS? 6394 04:17:53,760 --> 04:17:56,240 >> ABSOLUTELY. SO MANY WAYS. I 6395 04:17:56,240 --> 04:17:58,960 CAN GIVE ONE QUICK EXAMPLE, I 6396 04:17:58,960 --> 04:18:03,120 DON'T WANT TO TALK TOO MUCH BUT 6397 04:18:03,120 --> 04:18:06,120 ONE ONE OF THE KEY 6398 04:18:06,120 --> 04:18:07,240 NEUROBIOLOGICAL MECHANISMS 6399 04:18:07,240 --> 04:18:08,640 INFLUENCED BY INFLAMMATION AND 6400 04:18:08,640 --> 04:18:10,000 IS IMPORTANT FOR THE KIND OF 6401 04:18:10,000 --> 04:18:11,320 COGNITIVE DYSFUNCTION THAT 6402 04:18:11,320 --> 04:18:12,680 PEOPLE HAVE CHRONICALLY, IS 6403 04:18:12,680 --> 04:18:16,240 DISRUPTION OF MYELIN PLASTICITY 6404 04:18:16,240 --> 04:18:18,560 ONE MECHANISM THAT EBB ABLES 6405 04:18:18,560 --> 04:18:20,200 MYLOPLASTICITY IS SIGNALING 6406 04:18:20,200 --> 04:18:22,440 BRAIN DERIVED NEUROTROPIC 6407 04:18:22,440 --> 04:18:24,920 FACTOR, NEURONS AND OLIGO 6408 04:18:24,920 --> 04:18:27,360 OLIGODENDROCYTE PRECURSOR CELLS, 6409 04:18:27,360 --> 04:18:28,880 WE DON'T KNOW WHY BUT THAT IS A 6410 04:18:28,880 --> 04:18:32,400 CRITICAL PART OF WHY 6411 04:18:32,400 --> 04:18:34,160 CHEMOTHERAPY AT LEAST IN MICE 6412 04:18:34,160 --> 04:18:35,760 CAUSES WE THINK THIS KIND OF 6413 04:18:35,760 --> 04:18:37,720 IMPAIRMENT TO ATTENTION AND 6414 04:18:37,720 --> 04:18:40,720 MEMORY FUNCTION. SO BDNF IS AN 6415 04:18:40,720 --> 04:18:42,800 ACTIVITY REGULATED MOLECULE 6416 04:18:42,800 --> 04:18:44,800 IMPORTANT FOR NUMEROUS FORMS OF 6417 04:18:44,800 --> 04:18:48,040 NEURAL PLASTICITY DEVELOPMENTAL 6418 04:18:48,040 --> 04:18:50,680 HOMEOSAYSIS. EXERCISE INCREASES 6419 04:18:50,680 --> 04:18:52,880 IT, AS ONE EXAMPLE, SOCIAL 6420 04:18:52,880 --> 04:18:55,280 INTERACTIONS INCREASE BDNF 6421 04:18:55,280 --> 04:18:56,640 LEVELS IN THE BRAIN. THERE'S 6422 04:18:56,640 --> 04:18:59,160 LOTS OF WAYS TO START TO THINK 6423 04:18:59,160 --> 04:19:03,240 ABOUT HOW ENRICHED OR NOT OR 6424 04:19:03,240 --> 04:19:05,200 PAUCITY OF EXPERIENCE MIGHT BE 6425 04:19:05,200 --> 04:19:06,720 PLAYING A VERY IMPORTANT WAYS 6426 04:19:06,720 --> 04:19:08,920 INTO THE EXTENT TO WHICH CERTAIN 6427 04:19:08,920 --> 04:19:10,480 MECHANISMS OF PLASTICITY ARE 6428 04:19:10,480 --> 04:19:17,760 MAINTAINED OR NOT. 6429 04:19:17,760 --> 04:19:19,120 >> GOODS FOR THE BRAIN AND GOOD 6430 04:19:19,120 --> 04:19:22,880 FOR THE MUSCLE. WE HAVE FEW 6431 04:19:22,880 --> 04:19:26,360 YEARS AGO WE DID THE PILOT STUDY 6432 04:19:26,360 --> 04:19:28,840 ON MICE (INAUDIBLE) 6433 04:19:28,840 --> 04:19:33,040 CHARACTERIZED BY (INAUDIBLE) 6434 04:19:33,040 --> 04:19:35,960 WHETHER EXERCISE GOOD FOR 6435 04:19:35,960 --> 04:19:40,880 REDUCING MICE LIMITATIONS. WE 6436 04:19:40,880 --> 04:19:42,040 FOUND IT WAS GOOD AND WELL 6437 04:19:42,040 --> 04:19:45,160 TOLERATED AND GOOD FOR THE 6438 04:19:45,160 --> 04:19:48,200 MUSCLE, AND EVEN HOW WE PUT 6439 04:19:48,200 --> 04:19:49,280 (INAUDIBLE) POTENTIAL IMPACT AND 6440 04:19:49,280 --> 04:19:51,600 THERE ARE STUDIES SHOWING THAT 6441 04:19:51,600 --> 04:19:53,320 EXERCISE REDUCE INFLAMMATION OF 6442 04:19:53,320 --> 04:19:59,120 SYSTEMIC INFLAMMATION. , I I 6443 04:19:59,120 --> 04:20:01,800 THINK EXERCISE CAN BE GOOD. I 6444 04:20:01,800 --> 04:20:04,600 REMEMBER THE STUDY OF TOO MUCH 6445 04:20:04,600 --> 04:20:08,000 GWAS SHOWING THAT EXERCISE OR 6446 04:20:08,000 --> 04:20:12,040 OCCUPATIONAL THERAPY REDUCE 6447 04:20:12,040 --> 04:20:12,960 (INAUDIBLE) IT WAS EVEN BETTER 6448 04:20:12,960 --> 04:20:18,400 FOR THE BRAIN, REDUCING DELIRIUM 6449 04:20:18,400 --> 04:20:20,800 THEN IMPROVING THE MUSCLE 6450 04:20:20,800 --> 04:20:24,800 STRENGTH. 6451 04:20:24,800 --> 04:20:26,640 >> IN PRE-CLINICAL MODELS OF 6452 04:20:26,640 --> 04:20:30,280 METHYL TREXATE INDUCED COGNITIVE 6453 04:20:30,280 --> 04:20:31,560 IMPAIRMENT WHERE MICROGLIAL 6454 04:20:31,560 --> 04:20:33,680 REACTIVITY TARGETING THAT FIXING 6455 04:20:33,680 --> 04:20:35,280 THE PROBLEM SO TOO EVEN IN THE 6456 04:20:35,280 --> 04:20:38,760 CONTEXT OF INFLAMMATION ARE BDNF 6457 04:20:38,760 --> 04:20:40,840 AGONISTS SO WE HAVE A 2019 PAPER 6458 04:20:40,840 --> 04:20:45,080 PUBLISHED IN NEURON THAT SHOWS 6459 04:20:45,080 --> 04:20:46,600 THAT BDNF PARTIAL AGONIST SMALL 6460 04:20:46,600 --> 04:20:48,480 MOLECULE COMPOUND RESCUES 6461 04:20:48,480 --> 04:20:51,080 COGNITIVE FUNCTION AND RESTORE 6462 04:20:51,080 --> 04:20:52,440 MYELIN REGULATION AFTER ACUTE 6463 04:20:52,440 --> 04:20:54,360 THERAPY. SO WE CAN -- AS WE 6464 04:20:54,360 --> 04:20:55,960 UNDERSTAND SOME OF THESE 6465 04:20:55,960 --> 04:20:58,040 FACTORS, THERE ARE POTENTIAL 6466 04:20:58,040 --> 04:21:00,160 THERAPEUTIC AVENUES WHEN DRUGS 6467 04:21:00,160 --> 04:21:02,360 BECOME CLINICALLY AVAILABLE OF 6468 04:21:02,360 --> 04:21:04,680 COURSE A PRE-CLINICAL TOOL. 6469 04:21:04,680 --> 04:21:07,040 >> YOU SHOULD COMMENT ON THE 6470 04:21:07,040 --> 04:21:10,320 HEPARIN SULFATE AND LINK OF BDNF 6471 04:21:10,320 --> 04:21:12,920 TOO. 6472 04:21:12,920 --> 04:21:17,360 >> SO MY WORK TRAY GRACIOUS HI 6473 04:21:17,360 --> 04:21:18,920 FOCUSED ON ENDOTHELIAL INJURY 6474 04:21:18,920 --> 04:21:21,720 AND HOW IT IMPACTS BRAIN AS WELL 6475 04:21:21,720 --> 04:21:25,040 FROM INTERESTING -- HELIX WITH 6476 04:21:25,040 --> 04:21:26,920 HEAP RIP SULFATE CROSS IT IS 6477 04:21:26,920 --> 04:21:28,200 BLOOD BRAIN BARRIER TO THE 6478 04:21:28,200 --> 04:21:30,000 HIPPOCAMPUS AND ACTUALLY 6479 04:21:30,000 --> 04:21:32,120 INTERFERES WITH BDNF SIGNALING. 6480 04:21:32,120 --> 04:21:33,480 IT IS INTERESTING FOR YOU 6481 04:21:33,480 --> 04:21:35,720 MICHELLE, HEPARIN SULFATE PRO 6482 04:21:35,720 --> 04:21:37,200 OWE GLYCANS PRESENT IN THE BRAIN 6483 04:21:37,200 --> 04:21:40,880 MAYBE A FACTOR IN THIS BDNF 6484 04:21:40,880 --> 04:21:42,080 INTERACTION BETWEEN GLIA AND 6485 04:21:42,080 --> 04:21:43,960 NEURONS IS SOMETHING TO THINK 6486 04:21:43,960 --> 04:21:46,920 ABOUT. AND LOTS OF TOOLS TO PLAY 6487 04:21:46,920 --> 04:21:47,920 WITH IN GLYCO BIOLOGY OF THE 6488 04:21:47,920 --> 04:21:54,040 BRAIN. PROBABLY YEAH. THANK YOU 6489 04:21:54,040 --> 04:21:55,960 TRAY. 6490 04:21:55,960 --> 04:21:57,240 >> INTERESTING. 6491 04:21:57,240 --> 04:21:58,960 >> I WOULD LIKE TO ASK ALL OF 6492 04:21:58,960 --> 04:22:01,520 YOU A QUESTION THAT JIM JACK SOB 6493 04:22:01,520 --> 04:22:02,920 BROUGHT UP, IT -- JACKSON 6494 04:22:02,920 --> 04:22:05,400 BROUGHT UP, ALLUDED TO ALREADY. 6495 04:22:05,400 --> 04:22:06,840 BUT IN YOUR MIND ARE THERE 6496 04:22:06,840 --> 04:22:10,080 THERAPIES THAT ARE GOING ON BORN 6497 04:22:10,080 --> 04:22:11,080 FROM THE TRANSLATIONAL WORK WE 6498 04:22:11,080 --> 04:22:13,560 ARE DOING THAT'S BEEN ALLUDED TO 6499 04:22:13,560 --> 04:22:15,240 IN MOST OF YOUR TALKS. CAN YOU 6500 04:22:15,240 --> 04:22:16,920 PUT YOUR MONEY DOWN WHAT YOU 6501 04:22:16,920 --> 04:22:18,880 THINK IS THE MOST EFFECTIVE 6502 04:22:18,880 --> 04:22:21,680 TREATMENT FOR SURVIVORS. TAKE 6503 04:22:21,680 --> 04:22:22,680 HETEROGENOUS PATIENTS. TREAT 6504 04:22:22,680 --> 04:22:25,880 WITH ALL THE SAME PATIENTS 6505 04:22:25,880 --> 04:22:32,480 PHENOTYPING USING BIOMARKERS FOR 6506 04:22:32,480 --> 04:22:35,320 INFORMED TREATMENTS OR WITH THIS 6507 04:22:35,320 --> 04:22:41,160 ANTI-IL 6 THERAPY OR OTHERWISE? 6508 04:22:41,160 --> 04:22:46,240 >> I'M STRUCK BY HOW IL 6, NO 6509 04:22:46,240 --> 04:22:47,360 SKIN IN THE GAME, I DON'T HAVE 6510 04:22:47,360 --> 04:22:49,480 SHARES WITH IL 6 OR STOCK WITH 6511 04:22:49,480 --> 04:22:59,920 BIG IL 6 MORE TYPE SIMILAR 6512 04:23:02,760 --> 04:23:04,640 ASSOCIATIONS AND I THINK THIS -- 6513 04:23:04,640 --> 04:23:07,000 THE DATA I PRESENTED FROM 6514 04:23:07,000 --> 04:23:09,160 PATIENTS THAT IN COVID 6515 04:23:09,160 --> 04:23:12,480 POPULATION THAT IS EVEN MORE 6516 04:23:12,480 --> 04:23:15,000 HETEROGENOUS THAN AVERAGE ICU 6517 04:23:15,000 --> 04:23:16,520 PATIENT IS REALLY I THINK THAT 6518 04:23:16,520 --> 04:23:18,640 THAT IS WHERE IT IS AT, AT LEAST 6519 04:23:18,640 --> 04:23:21,920 WE NEED TO DO SOMETHING IN THAT 6520 04:23:21,920 --> 04:23:26,960 AREA. ANTI-IL 6 TREATMENT. 6521 04:23:26,960 --> 04:23:30,480 >> TO ADD TO THAT THE INFECTIOUS 6522 04:23:30,480 --> 04:23:31,920 HISTOPOPULATION IN PARTICULAR 6523 04:23:31,920 --> 04:23:33,400 WHICH FOOD ED TO TEST WHETHER 6524 04:23:33,400 --> 04:23:35,520 THERE'S EFFICACY IN MEDICAL OR 6525 04:23:35,520 --> 04:23:38,560 THERAPY AGAINST CYTOTOXIC TAU 6526 04:23:38,560 --> 04:23:41,040 VARIANTS. THAT HAS -- NEEDS TO 6527 04:23:41,040 --> 04:23:42,880 BE TESTED WE NEED TO SEE IF THAT 6528 04:23:42,880 --> 04:23:48,680 CAN BE EFFECTIVE. THERE ARE I 6529 04:23:48,680 --> 04:23:52,000 THINK LAST I LOOKED 13 CLINICAL 6530 04:23:52,000 --> 04:23:53,640 TRIALS WITH ANTI-TAU 6531 04:23:53,640 --> 04:23:55,280 IMMUNOTHERAPY CHRONIC 6532 04:23:55,280 --> 04:23:56,320 NEURODEGENERATIVE DISEASE, SOME 6533 04:23:56,320 --> 04:24:03,120 OF THE SAFETY TRIALS HAVE BEEN 6534 04:24:03,120 --> 04:24:05,640 SUCCESSFUL I THINK THERE IS GOOD 6535 04:24:05,640 --> 04:24:09,280 SPACE AND GOOD OPPORTUNITY TO 6536 04:24:09,280 --> 04:24:17,560 DEVELOP THAT AS CLINICAL TEST. 6537 04:24:17,560 --> 04:24:18,080 >> 6538 04:24:18,080 --> 04:24:24,840 >> MICHELLE? 6539 04:24:24,840 --> 04:24:26,560 >> I MEAN, I HAVE TO SAY I THINK 6540 04:24:26,560 --> 04:24:28,840 THERE ARE POTENTIAL CANDIDATE 6541 04:24:28,840 --> 04:24:30,520 THERAPIES BUT I REALLY STILL 6542 04:24:30,520 --> 04:24:32,040 THINK THERE NEEDS TO BE QUITE A 6543 04:24:32,040 --> 04:24:33,200 BIT OF PRE-CLINICAL WORK TO TEST 6544 04:24:33,200 --> 04:24:35,080 THOSE THERAPIES BEFORE YOU BRING 6545 04:24:35,080 --> 04:24:36,880 THEM FORWARD. SO THE MOLECULAR 6546 04:24:36,880 --> 04:24:38,160 COACHING OF MICROGLIA AND 6547 04:24:38,160 --> 04:24:39,720 TARGETING THE MECHANISMS OF 6548 04:24:39,720 --> 04:24:41,240 PLASTICITY AND HOMEOSTASIS THAT 6549 04:24:41,240 --> 04:24:44,080 THAT INFLAMMATION DISREGULATES 6550 04:24:44,080 --> 04:24:46,800 WILL PERHAPS BOTH IN IMPORTANT 6551 04:24:46,800 --> 04:24:48,520 STRATEGIES BUT I DON'T FEEL THAT 6552 04:24:48,520 --> 04:24:52,440 THERE IS A CLEAR WINNER IN MY 6553 04:24:52,440 --> 04:24:55,120 MIND TO WHAT WE NEED TO TARGET. 6554 04:24:55,120 --> 04:24:58,000 >> I THINK TARGETING THE 6555 04:24:58,000 --> 04:24:58,720 NEUROINFLAMMATORY PROCESS IS ONE 6556 04:24:58,720 --> 04:25:04,720 WAY. IN MY PRESENTATION WE 6557 04:25:04,720 --> 04:25:07,800 CARRY OUT CLINICAL TRIAL RELATED 6558 04:25:07,800 --> 04:25:10,400 TO (INAUDIBLE) WE FOUND EARLY 6559 04:25:10,400 --> 04:25:14,680 ACTIVATION OF AMYGDALA AND 6560 04:25:14,680 --> 04:25:16,960 PROTEASE ACTIVITY CAN OCCUR FROM 6561 04:25:16,960 --> 04:25:20,480 OCCURRENCE OF PTSD. IT WAS A 6562 04:25:20,480 --> 04:25:22,720 MOUSE MODEL AND WE FOUND THAT WE 6563 04:25:22,720 --> 04:25:26,840 HAVE TO REDUCE EARLY AMYGDALA 6564 04:25:26,840 --> 04:25:32,080 ACTIVATION OF PTSD, WHY WE 6565 04:25:32,080 --> 04:25:33,520 DECIDED TO DO THE CLINICAL 6566 04:25:33,520 --> 04:25:36,160 TRIAL. SO THERE ARE DIFFERENT 6567 04:25:36,160 --> 04:25:39,760 MECHANISMS AND THAT NOT THE SAME 6568 04:25:39,760 --> 04:25:42,080 EACH TIME BUT WE THOUGHT THIS 6569 04:25:42,080 --> 04:25:44,800 EARLY ACTIVATION COULD ACCOUNT 6570 04:25:44,800 --> 04:25:50,320 FOR SOME DISORDERS. IT WAS 6571 04:25:50,320 --> 04:25:51,200 CLINICAL PRE-CLINICAL FINDING 6572 04:25:51,200 --> 04:25:57,440 TRYING TO TRANSLATE TO PATIENTS. 6573 04:25:57,440 --> 04:26:02,320 FOR THE COMING YEARS IT IS 6574 04:26:02,320 --> 04:26:05,880 POSSIBLE AND THE (INAUDIBLE) 6575 04:26:05,880 --> 04:26:11,440 COULD BE NEGATIVE. 6576 04:26:11,440 --> 04:26:13,080 >> ALL RIGHT. LOOKS LIKE WE ARE 6577 04:26:13,080 --> 04:26:15,320 AT THE END OF THE SCHEDULED TIME 6578 04:26:15,320 --> 04:26:17,960 FOR THIS SESSION. THANK YOU SO 6579 04:26:17,960 --> 04:26:20,120 MUCH TO THE SPEAKERS AS WELL AS 6580 04:26:20,120 --> 04:26:22,720 ALL THE PARTICIPANTS FOR REALLY 6581 04:26:22,720 --> 04:26:23,600 THOUGHT-PROVOKING QUESTIONS IN 6582 04:26:23,600 --> 04:26:25,440 THE CHAT. I KNOW IT IS REALLY 6583 04:26:25,440 --> 04:26:27,160 LED ME TO THINK ABOUT SOME OF MY 6584 04:26:27,160 --> 04:26:31,160 OWN WORK IN A DIFFERENT WAY. 6585 04:26:31,160 --> 04:26:31,840 >> THANK YOU. 6586 04:26:31,840 --> 04:26:34,600 >> THANK YOU SO MUCH TO ALL THE 6587 04:26:34,600 --> 04:26:36,000 SUBSTITUTE SPEAKERS AND TO JOE 6588 04:26:36,000 --> 04:26:37,480 AND BEN FOR LEADING THE SESSION. 6589 04:26:37,480 --> 04:26:39,320 I HAVE TO TELL YOU ALL I WAS A 6590 04:26:39,320 --> 04:26:41,080 LITTLE BIT WORRIED WHEN I LOOKED 6591 04:26:41,080 --> 04:26:42,800 AT THE AGENDA AND I THOUGHT WOW 6592 04:26:42,800 --> 04:26:44,280 WE ARE GOING TO BE SITTING AT 6593 04:26:44,280 --> 04:26:46,120 COMPUTERS FOR A REALLY LONG 6594 04:26:46,120 --> 04:26:47,920 TIME. AND IT IS GOING TO BE 6595 04:26:47,920 --> 04:26:49,640 EXHAUSTING BUT AT LEAST FOR ME 6596 04:26:49,640 --> 04:26:52,480 IT WAS REALLY EXCITING AND I WAS 6597 04:26:52,480 --> 04:26:53,680 GLUED TO MY CHAIR THE WHOLE TIME 6598 04:26:53,680 --> 04:26:55,560 AND I'M LOOKING FORWARD TO 6599 04:26:55,560 --> 04:26:58,640 TOMORROW. I DO WANT TO POINT OUT 6600 04:26:58,640 --> 04:27:00,720 TO ALL OF YOU, IT LOOKS LIKE 6601 04:27:00,720 --> 04:27:02,640 THERE MAY BE A MISTAKE ON THE 6602 04:27:02,640 --> 04:27:05,680 AGENDA TOMORROW SO WE START AT 6603 04:27:05,680 --> 04:27:07,440 10 A.M. AND THE FIRST SPEAKER IS 6604 04:27:07,440 --> 04:27:11,400 AT 10:15 A.M., EASTERN STANDARD 6605 04:27:11,400 --> 04:27:12,480 TIME IN THE U.S. BUT THERE IS 6606 04:27:12,480 --> 04:27:15,240 ONE PART OF THE AGENDA SAYING 6607 04:27:15,240 --> 04:27:16,440 SESSION 3 AT 10:35. I DON'T 6608 04:27:16,440 --> 04:27:17,920 BELIEVE THAT'S CORRECT. MAYBE 6609 04:27:17,920 --> 04:27:19,360 SOMEBODY FROM NHLBI CAN CHIME 6610 04:27:19,360 --> 04:27:21,920 IN. SO THE PLAN TO START AT 10, 6611 04:27:21,920 --> 04:27:23,520 YOU SHOULD HAVE THE LINKS 6612 04:27:23,520 --> 04:27:24,840 TOMORROW, WE WILL HAVE ANOTHER 6613 04:27:24,840 --> 04:27:26,840 GREAT DAY WITH TWO SESSIONS AND 6614 04:27:26,840 --> 04:27:27,960 THEN BREAK OUT ROOMS AT THE END 6615 04:27:27,960 --> 04:27:30,000 OF THE DAY. PLEASE TUNE IN 6616 04:27:30,000 --> 04:27:31,480 AGAIN TOMORROW AND THANKS 6617 04:27:31,480 --> 04:27:32,520 EVERYONE FOR YOUR PARTICIPATION 6618 04:27:32,520 --> 04:27:42,680 TODAY.