1 00:00:07,111 --> 00:00:08,312 >> WELL, PEOPLE ARE STILL 2 00:00:08,312 --> 00:00:12,916 DRAFTING IN -- DRIFTING IN BUT 3 00:00:12,916 --> 00:00:15,586 I THINK IT'S TIME TO GET 4 00:00:15,586 --> 00:00:17,321 STARTED. I'M BOB, AND IT'S 5 00:00:17,321 --> 00:00:19,323 REALLY WITH GREAT PLEASURE THAT 6 00:00:19,323 --> 00:00:24,328 I ANNOUNCE AND INTRODUCE ROMNEY 7 00:00:24,328 --> 00:00:32,703 WHO IS A FELLOW IN THE 8 00:00:32,703 --> 00:00:34,972 MALIGNANCY BRANCH AND SHE'S 9 00:00:34,972 --> 00:00:37,141 GOING TO TALK ABOUT KA POE SI 10 00:00:37,141 --> 00:00:41,545 SAR ROMA AND HER TALK IS CALLED 11 00:00:41,545 --> 00:00:45,282 HIDDEN IN PLAIN SITE. KA POE SI 12 00:00:45,282 --> 00:00:48,185 SARCOMA AND OTHER 13 00:00:48,185 --> 00:00:49,353 KSHV-ASSOCIATED DISORDERS 14 00:00:49,353 --> 00:00:51,789 SHE DID HER TRAINING IN ENGLAND 15 00:00:51,789 --> 00:00:54,158 AND DID HER UNDERGRADUATE IN 16 00:00:54,158 --> 00:00:55,559 MEDICAL SCHOOL AND POSTGRADUATE 17 00:00:55,559 --> 00:00:57,728 TRAINING THERE IN THE IMPERIAL 18 00:00:57,728 --> 00:00:59,830 COLLEGE, ROYAL COLLEGE OF 19 00:00:59,830 --> 00:01:01,932 PHYSICIANS, INSTITUTE OF CANCER 20 00:01:01,932 --> 00:01:03,834 AND ALSO DID POSTGRADUATE 21 00:01:03,834 --> 00:01:04,601 TRAINING IN MEDICAL ONCOLOGY IN 22 00:01:04,601 --> 00:01:07,538 VARIOUS TEACHING HOSPITALS IN 23 00:01:07,538 --> 00:01:09,940 LONDON. DURING THIS PERIOD IN 24 00:01:09,940 --> 00:01:14,244 2014 SHE ALSO GOT A MASTER'S OF 25 00:01:14,244 --> 00:01:16,480 PUBLIC HEALTH FROM COLUMBIA 26 00:01:16,480 --> 00:01:18,215 UNIVERSITY. IN 2016 SHE CAME 27 00:01:18,215 --> 00:01:20,150 ACROSS THE POND TO BOSTON AND 28 00:01:20,150 --> 00:01:22,519 WORKED FOR A YEAR AS AN 29 00:01:22,519 --> 00:01:26,090 EDITORIAL FELLOW IN THE NEW 30 00:01:26,090 --> 00:01:27,358 ENGLAND JOURNAL WORKING WITH DAN 31 00:01:27,358 --> 00:01:29,126 LON GO I THINK MANY OF YOU KNOW 32 00:01:29,126 --> 00:01:32,363 HERE AND SHE JOINED THE BRANCH 33 00:01:32,363 --> 00:01:35,099 IN 2017. SHE CAME AS AN 34 00:01:35,099 --> 00:01:37,935 ASSISTANT RESEARCH PHYSICIAN 35 00:01:37,935 --> 00:01:42,706 THEN SHE WAS AN ACI AND BECAME A 36 00:01:42,706 --> 00:01:43,574 SCHOLAR THIS PAST FALL. SHE'S 37 00:01:43,574 --> 00:01:46,143 HAD A NUMBER OF AWARDS INCLUDING 38 00:01:46,143 --> 00:01:48,579 THE IMPERIAL COLLEGE OF MEDICINE 39 00:01:48,579 --> 00:01:52,049 COLORS AND THAT'S WITH A U. THE 40 00:01:52,049 --> 00:01:53,817 FEDERAL TECHNOLOGY TRANSFER 41 00:01:53,817 --> 00:01:56,453 AWARDS AND THE NCI DIRECTOR 42 00:01:56,453 --> 00:01:58,555 AWARD FOR DEI INITIATIVES. SHE 43 00:01:58,555 --> 00:02:00,290 IS A GOOD CITIZEN AND SERVES ON 44 00:02:00,290 --> 00:02:02,626 A NUMBER OF COMMITTEES INCLUDING 45 00:02:02,626 --> 00:02:05,696 THE NIH CDC GUIDELINES FOR 46 00:02:05,696 --> 00:02:07,197 OPPORTUNISTIC INFECTIONS. 47 00:02:07,197 --> 00:02:10,634 WHICH HAS NATIONAL IMPLICATIONS. 48 00:02:10,634 --> 00:02:13,303 THE INTERNATIONAL KSH ADVISORY 49 00:02:13,303 --> 00:02:14,338 COMMITTEE AND ALSO SERVES ON A 50 00:02:14,338 --> 00:02:17,641 NUMBER OF COMMITTEES HERE IN THE 51 00:02:17,641 --> 00:02:19,309 NIH INCLUDING THE SAFETY 52 00:02:19,309 --> 00:02:22,946 MONITORING COMMITTEE, THE BIO 53 00:02:22,946 --> 00:02:26,350 THERAPY COMMITTEE AND THE CANCER 54 00:02:26,350 --> 00:02:27,751 HEALTH DISPARITIES HEALTH 55 00:02:27,751 --> 00:02:28,619 COMMITTEE IN WHICH SHE'S BEEN 56 00:02:28,619 --> 00:02:35,793 THE CO-CHAIR SINCE 2021. HER 57 00:02:35,793 --> 00:02:39,096 RESEARCH IS ON THOSE CANCER 58 00:02:39,096 --> 00:02:41,965 CAUSED BY KSHV AND WITHOUT 59 00:02:41,965 --> 00:02:43,767 FURTHER ADO I WILL TURN THE 60 00:02:43,767 --> 00:02:50,174 PODIUM OVER TO THE DOCTOR. 61 00:02:50,174 --> 00:02:52,609 PLEASE GIVE HER A GOOD WELCOME. 62 00:02:52,609 --> 00:02:54,378 >> THANK YOU FOR THAT KIND 63 00:02:54,378 --> 00:02:56,346 INTRODUCTION. IT'S A DELIGHT TO 64 00:02:56,346 --> 00:02:57,748 BE HERE TODAY AND THANK YOU TO 65 00:02:57,748 --> 00:02:59,983 ALL TUNING IN AS WELL. WITH THE 66 00:02:59,983 --> 00:03:04,421 TITLE OF MY TALK IN KA POE SI 67 00:03:04,421 --> 00:03:05,155 SARCOMA IN GENERAL I THOUGHT WE 68 00:03:05,155 --> 00:03:08,292 WOULD START A LITTLE BIT IN THE 69 00:03:08,292 --> 00:03:10,294 PAST SO WHEN IT IS DESCRIBED IN 70 00:03:10,294 --> 00:03:17,534 THE 1800S IT WAS DEDOMINANTLY 71 00:03:17,534 --> 00:03:20,404 SEEN IN OLDER MEDITERRANEAN MEN 72 00:03:20,404 --> 00:03:21,538 AND IT WAS OBVIOUSLY VERY 73 00:03:21,538 --> 00:03:22,639 SURPRISING TO THE MEDICAL 74 00:03:22,639 --> 00:03:24,608 COMMUNITY AND THE ONCOLOGY 75 00:03:24,608 --> 00:03:27,244 COMMUNITY TO SEE OUTBREAKS OF 76 00:03:27,244 --> 00:03:28,946 THIS CONDITION AMONG YOUNG MEN 77 00:03:28,946 --> 00:03:32,049 WHO HAD SEX WITH MEN AND DYING 78 00:03:32,049 --> 00:03:36,053 FROM THIS DISEASE IN THE EARLY 79 00:03:36,053 --> 00:03:38,755 80S. AND WHAT HAPPENED 80 00:03:38,755 --> 00:03:40,958 SUBSEQUENT TO THAT IS THE 81 00:03:40,958 --> 00:03:42,659 IDENTIFICATION OF A VIRUS, HIV, 82 00:03:42,659 --> 00:03:46,296 THAT LED TO THE DEVELOPMENT OF 83 00:03:46,296 --> 00:03:49,967 ANTIRETROVIRAL THERAPY FIRST IN 84 00:03:49,967 --> 00:03:52,402 1987. THAT MANY INDIVIDUALS 85 00:03:52,402 --> 00:03:53,737 HERE IN THIS INSTITUTION PLAYED 86 00:03:53,737 --> 00:03:55,839 A ROLE IN THAT. BUT I ALSO WANT 87 00:03:55,839 --> 00:03:58,375 TO TAKE A MOMENT TO RECOGNIZE 88 00:03:58,375 --> 00:04:01,178 THE EFFORTS OF THE ADVOCACY 89 00:04:01,178 --> 00:04:03,247 COMMUNITY TO ENSURE WIDESPREAD 90 00:04:03,247 --> 00:04:06,350 DISSEMINATION OF THESE 91 00:04:06,350 --> 00:04:08,018 MEDICATIONS. AND THIS IS WHERE 92 00:04:08,018 --> 00:04:13,056 THE STORY DIVERGES BETWEEN HIV 93 00:04:13,056 --> 00:04:16,360 AND KAPOSI SARCOMA TO SOME 94 00:04:16,360 --> 00:04:18,095 DEGREE. AT THE TIME IT WAS 95 00:04:18,095 --> 00:04:20,030 UNCLEAR HOW THIS INITIAL 96 00:04:20,030 --> 00:04:22,299 HARBINGER OF HIV WAS ACTUALLY 97 00:04:22,299 --> 00:04:23,734 TRANSMITTED. WAS IT A VIRUS? 98 00:04:23,734 --> 00:04:26,069 WAS IT A SEXUALLY TRANSMITTED 99 00:04:26,069 --> 00:04:29,540 DISEASE? AND IT WAS ONLY IN 100 00:04:29,540 --> 00:04:35,379 1994 THAT CHANG AND MOORE 101 00:04:35,379 --> 00:04:38,749 DESCRIBED THIS VIRUS, YOU WILL 102 00:04:38,749 --> 00:04:41,618 HEAR ME REFER TO IT AS KSHV AND 103 00:04:41,618 --> 00:04:44,721 THIS VIRUS WAS ASSOCIATED WITH 104 00:04:44,721 --> 00:04:47,090 KS BUT ALSO WAS FOUND TO BE 105 00:04:47,090 --> 00:04:48,859 ASSOCIATED AND CAUSATIVE FOR 106 00:04:48,859 --> 00:04:52,963 OTHER ENTITIES SUCH AS PRIMARY 107 00:04:52,963 --> 00:04:54,798 EFFUSION LYMPHOMA AROUND THIS 108 00:04:54,798 --> 00:04:58,969 TIME THE DEVELOPMENT OF 109 00:04:58,969 --> 00:05:00,837 ANTIRETROVIRAL THERAPY WAS MUCH 110 00:05:00,837 --> 00:05:03,907 MORE SIGNIFICANT WITH 111 00:05:03,907 --> 00:05:04,975 COMBINATIONS AVAILABLE FOR 112 00:05:04,975 --> 00:05:06,076 PATIENTS AND THEN FURTHER 113 00:05:06,076 --> 00:05:07,077 THERAPIES WERE DEVELOPED IN THE 114 00:05:07,077 --> 00:05:13,250 EARLY PART OF THE 90S, DESPITE 115 00:05:13,250 --> 00:05:14,885 COMBINATION ANTIRETROVIRAL 116 00:05:14,885 --> 00:05:17,988 THERAPY WE CONTINUED TO SEE HIGH 117 00:05:17,988 --> 00:05:19,756 LEVELS OF KAPOSI SARCOMA AND 118 00:05:19,756 --> 00:05:25,195 PEOPLE DYING OF THIS DISEASE. 119 00:05:25,195 --> 00:05:26,129 WE THEN RECOGNIZED THIS WAS A 120 00:05:26,129 --> 00:05:32,536 GLOBAL ISSUE AND IN 2003 THE 121 00:05:32,536 --> 00:05:37,007 FUNDING WAS IDENTIFIED TO ENSURE 122 00:05:37,007 --> 00:05:42,279 THAT ANTIRETROVIRAL THERAPY WAS 123 00:05:42,279 --> 00:05:42,946 AVAILABLE. THERE ARE ONLY THREE 124 00:05:42,946 --> 00:05:45,616 CURRENT FDA APPROVED THERAPIES 125 00:05:45,616 --> 00:05:47,517 FOR KS AND THE MOST RECENT ONE 126 00:05:47,517 --> 00:05:54,324 WAS IN 2020 BASED ON WORK FROM 127 00:05:54,324 --> 00:05:56,426 US. WITH REGARDS TO KSHV WE 128 00:05:56,426 --> 00:06:00,063 KNOW THIS IS A DNA VIRUS, IT HAS 129 00:06:00,063 --> 00:06:02,399 TWO PROGRAMS. ONE WHICH IS OF 130 00:06:02,399 --> 00:06:04,134 LATENCY WHERE THE VIRUS IS ABLE 131 00:06:04,134 --> 00:06:07,037 TO PERSIST AND EXIST IN ITS OWN 132 00:06:07,037 --> 00:06:09,339 AND THE SECOND BEING PROGRAMS OF 133 00:06:09,339 --> 00:06:13,210 LIDDIC REPLICATION. THE 134 00:06:13,210 --> 00:06:16,246 INTERESTING THING ABOUT KSHV IS 135 00:06:16,246 --> 00:06:20,651 IT'S ABILITY OF HOST PROCESSES. 136 00:06:20,651 --> 00:06:22,986 TO EVADE THE HOST IMMUNE SYSTEM 137 00:06:22,986 --> 00:06:27,090 AND APOPTOSIS. IT'S ABILITY TO 138 00:06:27,090 --> 00:06:28,258 PROPAGATE ANGIOGENESIS, IT HAS 139 00:06:28,258 --> 00:06:30,761 ITS OWN CELL CYCLE COMPONENTS. 140 00:06:30,761 --> 00:06:34,698 AND IT ALSO HAS ITS OWN HOMOLOGS 141 00:06:34,698 --> 00:06:36,833 OF CYTOKINES. WHAT WE NOW KNOW 142 00:06:36,833 --> 00:06:39,102 ABOUT THIS VIRUS IS THAT IT IS 143 00:06:39,102 --> 00:06:41,371 HIGHLY PREVALENT IN SUB-SAHARAN 144 00:06:41,371 --> 00:06:42,606 AFRICA WHERE THERE ARE LIMITED 145 00:06:42,606 --> 00:06:43,774 RESOURCES, WHEREAS IN THE UNITED 146 00:06:43,774 --> 00:06:45,876 STATES, WE KNOW THAT IT'S 147 00:06:45,876 --> 00:06:47,277 PREDOMINANTLY TRANSMITTED AMONG 148 00:06:47,277 --> 00:06:53,750 THE MSM POPULATION. SO IN TERMS 149 00:06:53,750 --> 00:06:55,419 OF THE DISEASE MANIFESTATION IF 150 00:06:55,419 --> 00:06:57,721 WE PICK UP A TEXTBOOK ON THIS 151 00:06:57,721 --> 00:06:58,555 VIRUS WE RECOGNIZE THERE ARE 152 00:06:58,555 --> 00:07:01,925 FOUR PRINCIPLE CONDITIONS CAUSED 153 00:07:01,925 --> 00:07:08,398 BY KSHV. FIRST IS KA POE POSI 154 00:07:08,398 --> 00:07:12,002 SARCOMA SEEN ON THE SKIN AND IS 155 00:07:12,002 --> 00:07:13,737 FROM INFECTION AND ALSO MANIFEST 156 00:07:13,737 --> 00:07:17,974 IN THE GI TRACT OR IN THE LUNGS. 157 00:07:17,974 --> 00:07:20,877 THE SECOND IS MULTICENTRIC 158 00:07:20,877 --> 00:07:22,713 CASTLEMAN DISEASE AND THIS IS 159 00:07:22,713 --> 00:07:25,382 A -- IT'S A PLASMA KNOW PLASTIC 160 00:07:25,382 --> 00:07:28,452 FORM OF THIS DISEASE WHEN IT'S 161 00:07:28,452 --> 00:07:30,987 AFFECTED BY KSHV SEEN 162 00:07:30,987 --> 00:07:32,689 PREDOMINANTLY WITHIN PEOPLE WITH 163 00:07:32,689 --> 00:07:36,727 HIV. PATIENTS CAN HAVE SYSTEMIC 164 00:07:36,727 --> 00:07:39,096 SIDE EFFECTS. THERE'S A PET 165 00:07:39,096 --> 00:07:41,498 SCAN WHERE YOU CAN SEE 166 00:07:41,498 --> 00:07:43,200 WIDESPREAD LYMPHADENOPATHY AND 167 00:07:43,200 --> 00:07:45,168 INCREASE IN ORGAN SIZES. THESE 168 00:07:45,168 --> 00:07:46,970 PATIENTS CAN BE VERY UNWELL IF 169 00:07:46,970 --> 00:07:49,072 THIS DISEASE IS NOT IDENTIFIED 170 00:07:49,072 --> 00:07:51,108 PROMPTLY. THE THIRD DISEASE IS 171 00:07:51,108 --> 00:07:57,414 A TYPE OF NON-HODGKIN LYMPHOMA 172 00:07:57,414 --> 00:07:58,749 CALLED PRIMARY EFFUSION. WHERE 173 00:07:58,749 --> 00:07:59,549 YOU CAN SEE THE FLUID BETWEEN 174 00:07:59,549 --> 00:08:03,086 THE LUNG AND THE RIB SPACE. 175 00:08:03,086 --> 00:08:06,823 PATIENTS CAN AGAIN, BE VERY 176 00:08:06,823 --> 00:08:11,027 UNWELL WITH BREATHLESSLY. THIS 177 00:08:11,027 --> 00:08:13,697 ASSOCI 178 00:08:13,697 --> 00:08:18,335 ASSOCIATED CYTOKINE SYNDROME WAS 179 00:08:18,335 --> 00:08:20,871 FOUND IN 2006 AND IT IS A 180 00:08:20,871 --> 00:08:22,005 DIAGNOSIS OF EXCLUSION WHERE YOU 181 00:08:22,005 --> 00:08:26,743 HAVE TO RULE OUT CASTLEMAN, MCD 182 00:08:26,743 --> 00:08:29,045 O PEL. BUT AS THESE CONDITIONS 183 00:08:29,045 --> 00:08:32,082 WE SEE IN THEIR ENTIRETY. 184 00:08:32,082 --> 00:08:37,420 MCD, PEL AND KICS HAVE ELEVATED 185 00:08:37,420 --> 00:08:38,622 VIRUS LEVELS IN THE BLOOD AND WE 186 00:08:38,622 --> 00:08:42,359 SEE ALL OF THESE CONDITIONS 187 00:08:42,359 --> 00:08:44,327 DESPITE EXCELLENT HIV CONTROL OR 188 00:08:44,327 --> 00:08:46,396 HIGH CD4 COULDN'TS AS WELL. 189 00:08:46,396 --> 00:08:48,765 AND FROM HERE ON YOU'LL HEAR ME 190 00:08:48,765 --> 00:08:58,675 REFER TO MCD, PEL AND KICS AS 191 00:08:58,675 --> 00:09:00,610 KEDS. WE RECOGNIZE THESE 192 00:09:00,610 --> 00:09:05,048 DISEASES VERY WELL BUT THE 193 00:09:05,048 --> 00:09:08,785 REALITY IS THEY OFTEN OCCUR AS 194 00:09:08,785 --> 00:09:12,622 OVERLAPPING DISEASES AT THE SAME 195 00:09:12,622 --> 00:09:14,090 TIME AND AT MY TIME HERE WORKING 196 00:09:14,090 --> 00:09:15,792 AT THE BRANCH I REALIZED IT IS 197 00:09:15,792 --> 00:09:18,395 AN OVERLAP. THIS ONE VIRUS 198 00:09:18,395 --> 00:09:20,197 CAUSES NINE MANIFESTATIONS OF 199 00:09:20,197 --> 00:09:21,064 THE DISEASE IN DIFFERENT 200 00:09:21,064 --> 00:09:22,365 COMBINATIONS SO IN REALITY, WHAT 201 00:09:22,365 --> 00:09:25,468 WE SEE IS A PATIENT WHO IS 202 00:09:25,468 --> 00:09:27,237 SYSTEMICALLY UNWELL WITH 203 00:09:27,237 --> 00:09:29,472 EVIDENCE OF SOME KS ON THEIR 204 00:09:29,472 --> 00:09:31,608 SKIN CAN OFTEN BE LEFT WITH AN 205 00:09:31,608 --> 00:09:35,045 UNDIAGNOSED UNDERLYING PROCESS 206 00:09:35,045 --> 00:09:38,915 OFTEN ATTRIBUTED TO HIV. THIS 207 00:09:38,915 --> 00:09:41,685 PATIENT, FOR EXAMPLE, THEY HAVE 208 00:09:41,685 --> 00:09:44,321 IMAGING FINDINGS SUCH AS 209 00:09:44,321 --> 00:09:46,857 INTERSTITIAL INFEW TRACTS ON 210 00:09:46,857 --> 00:09:48,992 THEIR CT SCAN UP IN THE CORNER 211 00:09:48,992 --> 00:09:49,192 HERE. 212 00:09:49,192 --> 00:09:51,161 THEY MAY HAVE EFFUSIONS OR FLUID 213 00:09:51,161 --> 00:09:54,831 IN THEIR LUNGS, THEY MAY ALSO 214 00:09:54,831 --> 00:09:56,633 HAVE EVIDENCE OF ARROW THREE MA 215 00:09:56,633 --> 00:09:58,635 OR READINESS IN THEIR SCOPES AS 216 00:09:58,635 --> 00:10:01,037 WELL AS THE ENDOSCOPY OF THEIR 217 00:10:01,037 --> 00:10:02,873 STOMACH DUE TO SYMPTOMS. 218 00:10:02,873 --> 00:10:05,909 AND IT'S ONLY UNTIL AN EXPERT 219 00:10:05,909 --> 00:10:10,347 THAT PATHOLOGIST IS THAT WE'RE 220 00:10:10,347 --> 00:10:11,548 ABLE TO IDENTIFY MULTIPLE 221 00:10:11,548 --> 00:10:13,950 CONDITIONS IN THE SAME PATIENT. 222 00:10:13,950 --> 00:10:15,485 AS YOU CAN IMAGINE IF THEY WERE 223 00:10:15,485 --> 00:10:18,188 ON THE OUTSIDE THEY MAY JUST BE 224 00:10:18,188 --> 00:10:20,223 DIAGNOSED WITH SAR ROMA. IT 225 00:10:20,223 --> 00:10:22,158 BECOMES COMPLICATED VERY 226 00:10:22,158 --> 00:10:22,425 QUICKLY. 227 00:10:22,425 --> 00:10:25,228 THE OTHER ISSUE IS THAT THESE 228 00:10:25,228 --> 00:10:26,329 DISEASES AND THEIR 229 00:10:26,329 --> 00:10:30,834 MANIFESTATIONS OF KEDS CAN BE 230 00:10:30,834 --> 00:10:32,502 EXTREMELY RESOURCE INTENSIVE 231 00:10:32,502 --> 00:10:34,170 OFTEN REQUIRING PATIENT TO HAVE 232 00:10:34,170 --> 00:10:36,706 MULTIPLE BIOPSIES OF MULTIPLE 233 00:10:36,706 --> 00:10:40,744 ORGANS IN ORDER TO LEAD TO A 234 00:10:40,744 --> 00:10:44,414 DIAGNOSIS AND SO THIS INTENSIVE 235 00:10:44,414 --> 00:10:47,984 ABILITY TO PROCEDURALIZE AND 236 00:10:47,984 --> 00:10:49,986 DIAGNOSE OUR PATIENTS IS OFTEN 237 00:10:49,986 --> 00:10:51,454 CHALLENGING IN RESOURCE 238 00:10:51,454 --> 00:10:51,721 SETTINGS. 239 00:10:51,721 --> 00:10:53,023 AND WHY IS THIS IMPORTANT? 240 00:10:53,023 --> 00:10:54,991 BECAUSE IT DRIVES THE TREATMENT 241 00:10:54,991 --> 00:10:57,994 DECISION. IF YOU HAVE SOMEONE 242 00:10:57,994 --> 00:11:01,598 WITH KS WHO ACTUALLY HAS PEL OR 243 00:11:01,598 --> 00:11:03,500 CASTLEMAN'S THAT IS ACTUALLY A 244 00:11:03,500 --> 00:11:04,801 VERY DIFFERENT TREATMENT 245 00:11:04,801 --> 00:11:06,903 PARADIGM FROM JUST HAVING KS 246 00:11:06,903 --> 00:11:08,571 ALONE. 247 00:11:08,571 --> 00:11:10,206 AND SO IF YOU DON'T DIAGNOSE 248 00:11:10,206 --> 00:11:14,277 THESE KEDS APPROPRIATELY 249 00:11:14,277 --> 00:11:15,512 PATIENTS WILL BE SIMPLY 250 00:11:15,512 --> 00:11:18,114 DIAGNOSED WITH KS AND DIE FROM 251 00:11:18,114 --> 00:11:20,784 THEIR DISEASE AND SO AN 252 00:11:20,784 --> 00:11:21,384 APPROPRIATE DIAGNOSIS IS 253 00:11:21,384 --> 00:11:22,285 PARAMOUNT SO I WOULD LIKE TO 254 00:11:22,285 --> 00:11:24,754 TAKE YOU ALL TO THE THIRD FLOOR 255 00:11:24,754 --> 00:11:26,256 IN OUR INTENSIVE CARE UNIT HERE 256 00:11:26,256 --> 00:11:28,925 AT THE NCI AND THIS IS -- AT THE 257 00:11:28,925 --> 00:11:31,194 NIH, AND THIS IS WHERE OUR FIRST 258 00:11:31,194 --> 00:11:33,730 PROJECT STARTS. WE LOOKED BACK 259 00:11:33,730 --> 00:11:40,704 AT THE 42 PATIENTS WITH KEDS ALL 260 00:11:40,704 --> 00:11:42,472 OF WHOM HAD KD WITH ACTIVE 261 00:11:42,472 --> 00:11:44,908 DISEASE. SO, AGAIN, REMIND 262 00:11:44,908 --> 00:11:46,409 OURSELVES THAT ONE VIRUS CAUSES 263 00:11:46,409 --> 00:11:48,745 NINE MANIFESTATIONS OF THESE 264 00:11:48,745 --> 00:11:49,746 DISEASES. THESE WERE ALL 265 00:11:49,746 --> 00:11:52,349 PATIENTS WHO HAD FEVERS, WHO 266 00:11:52,349 --> 00:11:53,016 NEEDED INTENSIVE SUPPORT FOR 267 00:11:53,016 --> 00:11:55,719 THEIR BREATHING, OR THEIR 268 00:11:55,719 --> 00:11:57,020 CARDIOVASCULAR SYSTEM. THEY MAY 269 00:11:57,020 --> 00:11:59,923 NEED SUPPORT FOR THEIR KIDNEYS. 270 00:11:59,923 --> 00:12:04,194 AND THEY HAD THESE TENTATIVE 271 00:12:04,194 --> 00:12:07,097 DIAGNOSES WHICH WE HAD MADE AS 272 00:12:07,097 --> 00:12:09,099 EXPERTS IN THIS FIELD. AND WHAT 273 00:12:09,099 --> 00:12:12,669 I WANT TO DRAW YOUR EYE TO IS 274 00:12:12,669 --> 00:12:14,170 THE DIAGRAM OF DIAGNOSES THAT 275 00:12:14,170 --> 00:12:17,207 WERE NOTED AT THE TIME OF 276 00:12:17,207 --> 00:12:19,476 INITIAL ICU ADMISSION. WHAT WE 277 00:12:19,476 --> 00:12:22,245 FIND IS AS A GROUP OF 278 00:12:22,245 --> 00:12:24,481 PHYSICIANS, WE CONTINUED TO LOOK 279 00:12:24,481 --> 00:12:30,420 FOR DISORDERS CAUSED BY KSHV 280 00:12:30,420 --> 00:12:33,189 EVEN IN A CONDITION WHERE YOU 281 00:12:33,189 --> 00:12:38,161 HAD TO EXCLUDE MCD OR PEL. 282 00:12:38,161 --> 00:12:41,631 THESE WITH KS HAS KICS BEFORE 283 00:12:41,631 --> 00:12:43,800 THEY WENT TO THE ICU BUT WE 284 00:12:43,800 --> 00:12:45,335 CONTINUE TO LOOK IN THESE 285 00:12:45,335 --> 00:12:47,437 PATIENTS AND WE IDENTIFY THAT 286 00:12:47,437 --> 00:12:49,873 20% OF THESE INDIVIDUALS ENDED 287 00:12:49,873 --> 00:12:53,043 UP WITH MCD, PEL OR A 288 00:12:53,043 --> 00:12:54,110 COMBINATION OF THESE DISORDERS 289 00:12:54,110 --> 00:12:55,845 SO, AGAIN, THAT TELLS YOU THAT 290 00:12:55,845 --> 00:13:00,083 EVEN IN A PLACE LIKE THIS, EVEN 291 00:13:00,083 --> 00:13:01,384 WITH THE EXPERTISE, MAKING THESE 292 00:13:01,384 --> 00:13:05,688 DIAGNOSES ARE OFTEN EXTREMELY 293 00:13:05,688 --> 00:13:11,428 CHALLENGING. AND SO THATS US TO 294 00:13:11,428 --> 00:13:13,463 MY RESEARCH GOAL WHICH IS TO 295 00:13:13,463 --> 00:13:16,199 DEFINE THESE PATIENTS WITH KEDS. 296 00:13:16,199 --> 00:13:18,601 AND HOW THEY DIFFER FROM 297 00:13:18,601 --> 00:13:22,172 PATIENTS WITH KS ALONE. AND 298 00:13:22,172 --> 00:13:23,640 WITH THE LANDSCAPE IDENTIFYING 299 00:13:23,640 --> 00:13:27,077 THE CELL TYPES AND THE PATHWAYS 300 00:13:27,077 --> 00:13:29,045 THAT DRIVE THESE DIFFERENCES AND 301 00:13:29,045 --> 00:13:30,413 WOE NEED TO DO THIS IN ORDER TO 302 00:13:30,413 --> 00:13:33,416 DEVELOP BETTER OR -- SUPPORTIVE 303 00:13:33,416 --> 00:13:34,717 DIAGNOSTIC TOOLS IN LIMITED 304 00:13:34,717 --> 00:13:37,087 RESOURCE SETTINGS AND ALSO 305 00:13:37,087 --> 00:13:38,588 CONSIDER NEW THERAPEUTIC 306 00:13:38,588 --> 00:13:41,925 STRATEGIES FOR THESE DISORDERS. 307 00:13:41,925 --> 00:13:44,060 SO HOW WE'D LIKE TO DO THAT 308 00:13:44,060 --> 00:13:45,695 INITIALLY IS TO START WITH SOME 309 00:13:45,695 --> 00:13:49,032 OF OUR COHORTS THAT ARE 310 00:13:49,032 --> 00:13:50,467 HISTORICAL WITHIN THE THE HAM. 311 00:13:50,467 --> 00:13:52,502 I WOULD LIKE TO DRAW YOUR 312 00:13:52,502 --> 00:13:55,105 ATTENTION TO THESE THREE GRAPHS 313 00:13:55,105 --> 00:13:56,739 THESE ARE INFLAMMATORY CYTOKINES 314 00:13:56,739 --> 00:13:58,541 TAKEN THERE THE SERUM OF 315 00:13:58,541 --> 00:14:00,210 PATIENTS AT THE TIME OF ACTIVE 316 00:14:00,210 --> 00:14:02,011 DISEASE. I'D LIKE TO SHOW YOU 317 00:14:02,011 --> 00:14:04,948 THAT CLEARLY WHEN YOU HAVE KS, 318 00:14:04,948 --> 00:14:09,319 YOU HAVE A SLIGHTLY LOWER IN 319 00:14:09,319 --> 00:14:11,788 INFLAMMATORY COMPILE COMPARED TO 320 00:14:11,788 --> 00:14:13,556 SOMEONE WITH KICS AND ONCE YOU 321 00:14:13,556 --> 00:14:14,624 START THE PROFILE IT'S SIMILAR 322 00:14:14,624 --> 00:14:16,793 AMONG THESE GROUPS OFTEN. SO 323 00:14:16,793 --> 00:14:18,695 YOU CAN SEE THOSE WITH KICS AS 324 00:14:18,695 --> 00:14:21,698 COMPARED TO MCD OR PEL ARE 325 00:14:21,698 --> 00:14:23,032 LARGELY SIMILAR WHEREAS IF YOU 326 00:14:23,032 --> 00:14:25,168 HAVE KS YOUR INFLAMMATORY 327 00:14:25,168 --> 00:14:27,137 PROFILE IS SLIGHTLY MORE MUTED. 328 00:14:27,137 --> 00:14:30,306 AND THIS ACTUALLY TRANSLATES TO 329 00:14:30,306 --> 00:14:33,309 OUTCOMES BECAUSE WHEN WE THINK 330 00:14:33,309 --> 00:14:35,945 ABOUT THE -- WHEN YOU SEE THIS 331 00:14:35,945 --> 00:14:37,814 CURVE WE'RE ABLE TO LOOK AT THE 332 00:14:37,814 --> 00:14:40,350 SURVIVAL OUTCOMES WE SEE QUITE 333 00:14:40,350 --> 00:14:42,318 QUICKLY IN THE TOP LINE OF 334 00:14:42,318 --> 00:14:43,453 PATIENTS WITH KS ALONE THEY HAVE 335 00:14:43,453 --> 00:14:45,588 A MUCH BETTER SURVIVAL AS 336 00:14:45,588 --> 00:14:49,592 COMPARED TO HAVING AN 337 00:14:49,592 --> 00:14:54,430 INFLAMMATORY CONDITION SUCH AS 338 00:14:54,430 --> 00:14:57,901 MCD, KICS OR PEL. IT ASKS THE 339 00:14:57,901 --> 00:15:01,738 QUESTION WE CLEARLY SEE 340 00:15:01,738 --> 00:15:04,440 INFLAMMATION AS AN IMPORTANT 341 00:15:04,440 --> 00:15:06,943 COMPONENT IN KEDS BUT IS IT A 342 00:15:06,943 --> 00:15:11,814 DRIVER A BYSTANDER OR HOW CAN WE 343 00:15:11,814 --> 00:15:13,650 THINK ABOUT THERAPIES WHEN WE 344 00:15:13,650 --> 00:15:14,984 ADDRESS THESE INFLAMMATORY 345 00:15:14,984 --> 00:15:16,686 PROFILES. OFTEN WHEN I GIVE 346 00:15:16,686 --> 00:15:19,322 THESE TALKS I'M OFTEN ASKED YOU 347 00:15:19,322 --> 00:15:22,225 SEE IL-6 ELEVATED IS THAT A 348 00:15:22,225 --> 00:15:23,092 THERAPEUTIC TARGET AND IN OUR 349 00:15:23,092 --> 00:15:27,096 BRAND WE HAVE LOOKED AT IL-6 AS 350 00:15:27,096 --> 00:15:29,032 A THERAPEUTIC TARGET AND WE HAVE 351 00:15:29,032 --> 00:15:30,767 STUDIED CASTLEMAN DISEASE WHERE 352 00:15:30,767 --> 00:15:33,603 WE KNOW THERE'S ELEVATED IL-6 IN 353 00:15:33,603 --> 00:15:37,140 THE BLOOD AS I JUST SHOWED YOU 354 00:15:37,140 --> 00:15:39,842 AND WE USED THE RECEPTOR 355 00:15:39,842 --> 00:15:41,377 INHIBITOR IN EIGHT PATIENTS WITH 356 00:15:41,377 --> 00:15:44,581 HIV AND CASTLEMAN DISORDER. 357 00:15:44,581 --> 00:15:47,050 CASTLEMAN DISEASE, TWO OF WHOM 358 00:15:47,050 --> 00:15:49,552 ALSO HAD CONCURRENT KS. OF FIVE 359 00:15:49,552 --> 00:15:52,255 OF THE EIGHT PATIENTS HAD A 360 00:15:52,255 --> 00:15:53,756 RESPONSE IN THEIR CASTLEMAN'S 361 00:15:53,756 --> 00:15:55,491 BUT THIS WAS OFTEN A TEMPORARY 362 00:15:55,491 --> 00:15:57,093 RESPONSE. AND MOST OF THESE 363 00:15:57,093 --> 00:16:01,598 PATIENTS ENDED UP HAVING 364 00:16:01,598 --> 00:16:02,699 SUBSEQUENT WORSTENING OF THEIR 365 00:16:02,699 --> 00:16:03,533 CASTLEMAN'S REQUIRING THE 366 00:16:03,533 --> 00:16:05,702 STANDARD OF CARE WHICH IS A 367 00:16:05,702 --> 00:16:09,105 B-CELL DEPLETING THERAPY CALLED 368 00:16:09,105 --> 00:16:11,841 RETOX MAB. WE ASKED, WHY IS 369 00:16:11,841 --> 00:16:14,611 THIS? WE HAVE CLEARLY SEEN IL-6 370 00:16:14,611 --> 00:16:16,312 ELEVATED IN THE BLOOD WHY ARE WE 371 00:16:16,312 --> 00:16:17,880 SEEING LACK OF RESPONSE AND THE 372 00:16:17,880 --> 00:16:21,484 ANSWER TO THIS COMES FROM THE 373 00:16:21,484 --> 00:16:32,128 VIRUS ITSELF. KSHV IS AVAILABLE 374 00:16:32,528 --> 00:16:37,734 TO BYPASS THE IL-6 RECEPTOR SO 375 00:16:37,734 --> 00:16:38,368 EVEN THOUGH WE'RE INHIBITING IT 376 00:16:38,368 --> 00:16:39,802 IT IS STILL ABLE TO TRIGGER THE 377 00:16:39,802 --> 00:16:43,640 DOWNSTREAM PROCESSES. SO I'D 378 00:16:43,640 --> 00:16:45,108 LIKE TO TAKE A STEP FURTHER UP 379 00:16:45,108 --> 00:16:48,278 AND THINK ABOUT THE UPSTREAM 380 00:16:48,278 --> 00:16:49,512 PROCESSES FROM CYTOKINE 381 00:16:49,512 --> 00:16:52,849 PRODUCTION AND TALK A LITTLE BIT 382 00:16:52,849 --> 00:16:54,150 ABOUT THE APPLICATION. SO 383 00:16:54,150 --> 00:16:55,718 UNDERSTANDING THE PATHWAYS OF 384 00:16:55,718 --> 00:17:00,490 STREAM OF INFLAMMATION OF THESE 385 00:17:00,490 --> 00:17:01,457 INFLAMMATORY CYTOKINES MAY HELP 386 00:17:01,457 --> 00:17:05,028 US UNDERSTAND THE PATHOGENESIS 387 00:17:05,028 --> 00:17:07,230 OF KEDS, HELP US IDENTIFY NEW 388 00:17:07,230 --> 00:17:09,532 DIAGNOSTIC METHODS AND MAY ALSO 389 00:17:09,532 --> 00:17:12,835 OFFER NEW THERAPEUTIC 390 00:17:12,835 --> 00:17:19,208 OPPORTUNITIES. THE INFLAMMASOME 391 00:17:19,208 --> 00:17:23,112 ITSELF CONTROLS THE RESPONSE AND 392 00:17:23,112 --> 00:17:25,448 IMMUNE RESPONSE AGAINST 393 00:17:25,448 --> 00:17:26,616 INFECTIOUS AGENTS AND LEADS TO 394 00:17:26,616 --> 00:17:28,418 CELL DEATH. AND THIS IS KNOWN 395 00:17:28,418 --> 00:17:32,922 TO BE -- IS NOTABLE IN SEVERAL 396 00:17:32,922 --> 00:17:35,992 DISORDERS INCLUDING HIV AND 397 00:17:35,992 --> 00:17:39,262 CANCER. AND I'D LIKE TO NOTE 398 00:17:39,262 --> 00:17:44,667 THAT THE LAB HERE IN NIAD HAVE 399 00:17:44,667 --> 00:17:47,170 BEEN LEADERS IN IDENTIFYING 400 00:17:47,170 --> 00:17:49,472 ACTIVATION IN SEVERAL HIV 401 00:17:49,472 --> 00:17:51,307 ASSOCIATED DISORDERS AND THOSE 402 00:17:51,307 --> 00:17:52,809 ASSOCIATED WITH OPPORTUNISTIC 403 00:17:52,809 --> 00:17:53,976 INFECTIONS IN THOSE WITH HIV. 404 00:17:53,976 --> 00:17:55,078 SO I'D LIKE TO GO INTO A LITTLE 405 00:17:55,078 --> 00:17:57,580 BIT OF THE DETAILS IN WHAT THE 406 00:17:57,580 --> 00:17:59,048 INFLAMMASOME IS AND YOU CAN SEE 407 00:17:59,048 --> 00:18:03,086 THAT IN THE FIGURE ON THE LEFT. 408 00:18:03,086 --> 00:18:06,656 THE INFLAMMASOME CYTOKINE 409 00:18:06,656 --> 00:18:07,190 REQUIRE THE INFLAMMASOME 410 00:18:07,190 --> 00:18:08,691 ACTIVATION AND HOW THIS WORKS IS 411 00:18:08,691 --> 00:18:12,829 IT REQUIRES THREE PRINCIPLE 412 00:18:12,829 --> 00:18:14,964 COMPONENTS. THE FIRST IS A NOD 413 00:18:14,964 --> 00:18:17,467 LIKE RECEPTOR THE SECOND IS THE 414 00:18:17,467 --> 00:18:21,904 APOPTOSIS ASSOCIATED SPECK LIKE 415 00:18:21,904 --> 00:18:25,308 PROTEIN CONTAINING A CARD SO 416 00:18:25,308 --> 00:18:29,679 YOU'LL HEAR ME REFER TO THIS AS 417 00:18:29,679 --> 00:18:33,316 ASC AND THEN THE SPACE ONE WHICH 418 00:18:33,316 --> 00:18:35,585 IS THE MOST COMMON ACTIVATED 419 00:18:35,585 --> 00:18:38,654 SPACE. SO IN THIS 420 00:18:38,654 --> 00:18:40,390 COLLABORATION, WITH THE SIR 421 00:18:40,390 --> 00:18:42,959 LETTY LAB WE LOOKED AT PATIENTS 422 00:18:42,959 --> 00:18:45,928 WITH KED AND LOOKED AT THEIR 423 00:18:45,928 --> 00:18:47,063 PERIPHERAL BLOOD SAMPLES DURING 424 00:18:47,063 --> 00:18:51,100 A PERIOD OF ACTIVE DISEASE. 425 00:18:51,100 --> 00:18:54,704 WE LOOKED AT THE ASC AGGREGATES 426 00:18:54,704 --> 00:18:57,407 IN PARTICIPANT SAMPLES USING 427 00:18:57,407 --> 00:18:58,474 IMAGE STREAM SPECIFICALLY 428 00:18:58,474 --> 00:19:00,676 LOOKING AT MONOCYTES BY 429 00:19:00,676 --> 00:19:03,446 SELECTING THE CD 14 POSITIVE 430 00:19:03,446 --> 00:19:09,051 CELLS SO UPON TRIGGERING OF THE 431 00:19:09,051 --> 00:19:10,486 INFLAMMASOME SENSORS THIS 432 00:19:10,486 --> 00:19:13,022 RING-LIKE STRUCTURE WHICH IS AN 433 00:19:13,022 --> 00:19:16,459 ASC SPECK AND A MARKER OF 434 00:19:16,459 --> 00:19:19,061 CANONICAL ACTIVATION WAS 435 00:19:19,061 --> 00:19:23,466 DETECTED BY FLUORESCENCE 436 00:19:23,466 --> 00:19:25,701 MICROSCOPY, THIS EXPERIMENT DONE 437 00:19:25,701 --> 00:19:31,073 THAT WERE PREINCUBATED CELLS WAS 438 00:19:31,073 --> 00:19:33,309 FOLLOWED BY IMMUNO PHENOTYPING 439 00:19:33,309 --> 00:19:34,911 AND INTRACELLULAR STAINING. SO 440 00:19:34,911 --> 00:19:39,081 BY DOING THIS WE WERE ABLE TO 441 00:19:39,081 --> 00:19:43,653 SCREEN FOR FLICKER POSITIVE ASC 442 00:19:43,653 --> 00:19:44,754 AGGREGATES WITHIN BLOOD CELLS IN 443 00:19:44,754 --> 00:19:47,056 ADDITION WE ALSO MEASURED THE 444 00:19:47,056 --> 00:19:49,892 INFLAMMATORY CYTOKINES WHICH 445 00:19:49,892 --> 00:19:55,097 INCLUDED IO 1 BETA AND HAD TWO 446 00:19:55,097 --> 00:19:56,299 ADDITIONAL COMPARATOR GROUPS THE 447 00:19:56,299 --> 00:19:58,234 FIRST BEING THOSE WHO ARE HIV 448 00:19:58,234 --> 00:20:00,536 NEGATIVE VOLUNTEER OR HVS AND 449 00:20:00,536 --> 00:20:02,839 THOSE WHO WERE PEOPLE WITH HIV 450 00:20:02,839 --> 00:20:07,076 WITHOUT KEDS AT ALL SO 451 00:20:07,076 --> 00:20:10,680 INTERESTINGLY THE INFLAMMASOME 452 00:20:10,680 --> 00:20:12,148 ACTIVATION AS YOU CAN SEE BY THE 453 00:20:12,148 --> 00:20:17,086 FLICKER WAS INCREASED IN THOSE 454 00:20:17,086 --> 00:20:20,890 WITH KEDS AS COMPARED TO THOSE 455 00:20:20,890 --> 00:20:22,658 WHO WERE HEALTHY VOLUNTEERS AND 456 00:20:22,658 --> 00:20:25,561 IL-18 WAS ALSO INCREASED AS 457 00:20:25,561 --> 00:20:27,129 COMPARED TO PEOPLE WITH HIV AND 458 00:20:27,129 --> 00:20:29,065 HEALTHY VOLUNTEERS. IT WAS 459 00:20:29,065 --> 00:20:35,204 NOTABLE THAT THOSE VOYINDIVIDUA 460 00:20:35,204 --> 00:20:43,579 WHEN COMPARING THOSE WITH W KD 461 00:20:43,579 --> 00:20:44,747 AND HIV THEY WERE ALMOST SIMILAR 462 00:20:44,747 --> 00:20:48,417 TO THE DISEASE PROCESSES IN BOTH 463 00:20:48,417 --> 00:20:49,185 GROUPS. 464 00:20:49,185 --> 00:20:51,120 INTERESTINGLY WE ALSO NOTED THAT 465 00:20:51,120 --> 00:20:54,290 FLICKER WAS CORRELATING WITH 466 00:20:54,290 --> 00:20:57,093 KSHV AND WITH IL-6 AND 10 467 00:20:57,093 --> 00:20:58,427 FURTHER INDICATING THE ROLE OF 468 00:20:58,427 --> 00:21:02,164 THE VIRUS IN THIS PROCESS. WE 469 00:21:02,164 --> 00:21:05,167 WERE ALSO ABLE TO DELINEATE IN 470 00:21:05,167 --> 00:21:08,804 THIS PCA ALL THE MARKERS OF 471 00:21:08,804 --> 00:21:09,772 INFLAMMASOME ACTIVATION IN 472 00:21:09,772 --> 00:21:11,073 ADDITION TO THE INFLAMMATORY 473 00:21:11,073 --> 00:21:12,675 BIOMARKERS AND WE SEE IN THE 474 00:21:12,675 --> 00:21:15,077 VARIOUS COLORED GROUPS 475 00:21:15,077 --> 00:21:17,713 SEPARATION OF KEDS THEMSELVES. 476 00:21:17,713 --> 00:21:20,182 YOU CAN SEE THAT INDIVIDUALS 477 00:21:20,182 --> 00:21:24,720 WITH PEL AND KS IN THE BLUE AND 478 00:21:24,720 --> 00:21:25,788 GREEN RESPECTIVELY DO CLUSTER 479 00:21:25,788 --> 00:21:28,157 TOGETHER WHEREAS THOSE WITH MCD 480 00:21:28,157 --> 00:21:31,093 SEEM TO BE SOMEWHAT DIFFERENT. 481 00:21:31,093 --> 00:21:32,995 PERHAPS IDENTIFYING DELINEATIONS 482 00:21:32,995 --> 00:21:34,931 IN THE INFLAMMASOME ACTIVATION 483 00:21:34,931 --> 00:21:38,067 PATHWAYS BETWEEN THESE DISEASES. 484 00:21:38,067 --> 00:21:39,902 AS A FOLLOW UP TO THIS WORK, 485 00:21:39,902 --> 00:21:44,040 WE'VE ALSO SEEN THAT IL-18 IS A 486 00:21:44,040 --> 00:21:46,943 MARKER OF POTENTIAL DIAGNOSTIC 487 00:21:46,943 --> 00:21:49,145 MARKER THAT CAN SEPARATE THIS 488 00:21:49,145 --> 00:21:52,582 KED PROCESS AS COMPARED TO OTHER 489 00:21:52,582 --> 00:21:54,517 OPPORTUNISTIC INFECTIONS IN 490 00:21:54,517 --> 00:21:56,152 PEOPLE WITH HIV. SO THIS IS 491 00:21:56,152 --> 00:21:59,221 WORK THAT WITHIN THE SIR LETTY 492 00:21:59,221 --> 00:22:01,257 LAB THE DOCTOR WILL BE PURSUING 493 00:22:01,257 --> 00:22:04,327 AS WE MOVE FORWARD. 494 00:22:04,327 --> 00:22:06,395 SO SO FAR WHAT I'VE TAKEN YOU 495 00:22:06,395 --> 00:22:08,197 THROUGH IS CLEAR EVIDENCE OF 496 00:22:08,197 --> 00:22:10,032 INFLAMMATION IN THE SERUM. IN 497 00:22:10,032 --> 00:22:13,302 OUR PBMCS WE'VE SEEN THE 498 00:22:13,302 --> 00:22:16,038 INFLAMMASOME ACTIVATION, THAT 499 00:22:16,038 --> 00:22:18,975 SEEMS TO BE DISTINCT BY KEDS. 500 00:22:18,975 --> 00:22:22,011 IT SEEMS WE ARE VERY LUCKY IN 501 00:22:22,011 --> 00:22:23,412 THE WORK THAT WE DO THAT WE ARE 502 00:22:23,412 --> 00:22:26,148 ABLE TO ACCESS TUMORS FOR EASILY 503 00:22:26,148 --> 00:22:28,150 BECAUSE FORTUNATELY AND 504 00:22:28,150 --> 00:22:30,019 UNFORTUNATELY, THEY'RE ON THE 505 00:22:30,019 --> 00:22:31,988 SKIN SO THE NATURAL QUESTION 506 00:22:31,988 --> 00:22:33,422 BECOMES WHAT DO THE TUMORS 507 00:22:33,422 --> 00:22:34,590 THEMSELVES TELL US AND THIS IS 508 00:22:34,590 --> 00:22:38,194 WORK THAT I WAS VERY EXCITED TO 509 00:22:38,194 --> 00:22:41,030 DO WITH MY COLLEAGUE, JOE IN THE 510 00:22:41,030 --> 00:22:42,665 HAM, LOOKING AT PATIENTS WITH KS 511 00:22:42,665 --> 00:22:45,568 BOTH ON THEIR SKIN AND IN THEIR 512 00:22:45,568 --> 00:22:50,606 GI TRACT SO IN 22 KS SPECIMENS 513 00:22:50,606 --> 00:22:53,075 WE LOOKED AT THOSE -- TEN 514 00:22:53,075 --> 00:22:55,511 PATIENTS WHO JUST HAD SKIN AND 515 00:22:55,511 --> 00:22:59,148 TWELVE OF WHOM HAD GI KS WE GOT 516 00:22:59,148 --> 00:23:01,550 COMPARED BOTH NORMAL AND KS IN 517 00:23:01,550 --> 00:23:05,087 BOTH SITES. AND THIS WAS BOTH 518 00:23:05,087 --> 00:23:10,459 RNA SEQUENCING THAT WAS DONE. 519 00:23:10,459 --> 00:23:12,261 THREE OF THE PATIENTS THAT HAD 520 00:23:12,261 --> 00:23:16,532 SKIN AND GI KS. WE DID BULK RNA 521 00:23:16,532 --> 00:23:20,536 SEQUENCING THAT ALSO INCLUDED 522 00:23:20,536 --> 00:23:23,105 KSH VGS AND THERE WAS AN OVERLAP 523 00:23:23,105 --> 00:23:25,775 OF 26 GENES BETWEEN THESE SITES 524 00:23:25,775 --> 00:23:27,076 AND INTERESTINGLY WHEN WE LOOK 525 00:23:27,076 --> 00:23:29,612 AT THESE 26 GENES THERE ARE TWO 526 00:23:29,612 --> 00:23:32,882 THAT POP UP AS PARTICULARLY 527 00:23:32,882 --> 00:23:35,017 INTERESTING SDC 1 WHICH IS A 528 00:23:35,017 --> 00:23:40,756 GLYCOPROTEIN THAT REGULATES 529 00:23:40,756 --> 00:23:43,159 FACTORS IN PEOPLE AND HAVE BEEN 530 00:23:43,159 --> 00:23:44,493 A CONTRIBUTING TO CAR SIN KNOW 531 00:23:44,493 --> 00:23:47,063 GENESIS AS DESCRIBED IN THE 532 00:23:47,063 --> 00:23:47,363 LITERATURE. 533 00:23:47,363 --> 00:23:50,366 FLIT FOUR HAS BEEN NOTED TO 534 00:23:50,366 --> 00:23:53,502 REGULATE THE LYMPHATIC SYSTEM 535 00:23:53,502 --> 00:23:55,538 AND TOGETHER THE DOCTOR'S GROUP 536 00:23:55,538 --> 00:23:57,773 HAS DONE SOME VERY ELEGANT 537 00:23:57,773 --> 00:24:00,276 EXPERIMENTING SHOWING THE ROLE 538 00:24:00,276 --> 00:24:06,148 OF SDC ONE. AND I URGE YOU TO 539 00:24:06,148 --> 00:24:08,250 READ OUR PAPER FROM LAST YEAR. 540 00:24:08,250 --> 00:24:09,719 AMONG THESE PARTICIPANTS OF 19 541 00:24:09,719 --> 00:24:13,255 AS I MENTIONED, 74 ACTUALLY HAD 542 00:24:13,255 --> 00:24:17,727 CONCURRENT KEDS AND WHEN WE LOOK 543 00:24:17,727 --> 00:24:20,996 ACROSS SKIN VERSUS -- SKIN KS 544 00:24:20,996 --> 00:24:22,431 VERSUS NORMAL WE SEE THAT THERE 545 00:24:22,431 --> 00:24:26,035 ARE INCREASED IL-6 LEVELS IN 546 00:24:26,035 --> 00:24:28,337 THOSE KS LESIONS AS COMPARED TO 547 00:24:28,337 --> 00:24:29,905 ADJACENT SKIN THAT'S NORMAL AND 548 00:24:29,905 --> 00:24:33,042 THIS IS MORE TRUE AS COMPARED TO 549 00:24:33,042 --> 00:24:34,677 GI KS WHICH IS PARTICULARLY 550 00:24:34,677 --> 00:24:38,647 INTERESTING AND IN PATIENTS WHO 551 00:24:38,647 --> 00:24:43,886 HAD SKIN KS AS COMPARED TO THEIR 552 00:24:43,886 --> 00:24:47,056 NORMAL ADJACENT TISSUES THE IL-6 553 00:24:47,056 --> 00:24:49,558 GENE EXPRESSION ACTUALLY 554 00:24:49,558 --> 00:24:50,493 COORDINATED WITH THE GENE 555 00:24:50,493 --> 00:24:52,194 EXPRESSION PROFILING MIMICKING 556 00:24:52,194 --> 00:24:55,564 WHAT WE SEE IN THE CIRCULATION. 557 00:24:55,564 --> 00:24:57,466 SO WHEN WE LOOK TO SEE, WELL, 558 00:24:57,466 --> 00:24:59,135 CAN THE SKIN LESIONS OR THE GI 559 00:24:59,135 --> 00:25:01,036 LESIONS GIVE US AN INDICATION OF 560 00:25:01,036 --> 00:25:02,972 A POTENTIAL BIOMARKER SO IF YOU 561 00:25:02,972 --> 00:25:05,074 WERE IN THE CLINIC AND YOU TOOK 562 00:25:05,074 --> 00:25:06,842 A SKIN SAMPLE, WENT BACK AND 563 00:25:06,842 --> 00:25:08,811 WERE ABLE TO SEQUENCE IT, ARE 564 00:25:08,811 --> 00:25:10,012 THERE ANY PARTICULAR GENES THAT 565 00:25:10,012 --> 00:25:12,748 WOULD TELL US OH, THIS PATIENT 566 00:25:12,748 --> 00:25:16,919 ALSO HAS LYMPHOMA OR PEL OR MCD 567 00:25:16,919 --> 00:25:19,088 OR KICS WE LOOK TO SEE WHETHER 568 00:25:19,088 --> 00:25:20,890 THERE WAS ANYTHING SIGNIFICANT 569 00:25:20,890 --> 00:25:21,457 AMONG THE CYTOKINES AND WE 570 00:25:21,457 --> 00:25:24,794 DIDN'T SEE ANY GENES THAT WERE 571 00:25:24,794 --> 00:25:25,828 SIGNIFICANTLY DIFFERENT BETWEEN 572 00:25:25,828 --> 00:25:33,803 KS AND OTHER KEDS. WE DID 573 00:25:33,803 --> 00:25:35,905 IDENTIFY ONE GENE THAT WAS 574 00:25:35,905 --> 00:25:39,675 NOTABLE IN PROSTATE CANCER CELL 575 00:25:39,675 --> 00:25:43,846 LINES THAT MAY BE HIGHER IN 576 00:25:43,846 --> 00:25:46,315 THOSE WITH KS ALONE. THIS IS 577 00:25:46,315 --> 00:25:47,483 ALSO NOTED IN THE LITERATURE TO 578 00:25:47,483 --> 00:25:50,319 BE A TUMOR SUPPRESSOR GENE. 579 00:25:50,319 --> 00:25:53,289 WHEN WE LOOK ACROSS SPECIFICALLY 580 00:25:53,289 --> 00:25:54,723 THE GENE EXPRESSION PROFILES IN 581 00:25:54,723 --> 00:25:57,526 THESE TUMORS, AGAIN, GI VERSUS 582 00:25:57,526 --> 00:25:59,695 SKIN IN THE THREE PARTICIPANTS 583 00:25:59,695 --> 00:26:01,897 WHO HAD BOTH, WE SEE 584 00:26:01,897 --> 00:26:03,966 COMMONALITIES WITH THE LATENCY 585 00:26:03,966 --> 00:26:08,270 PROGRAM ACROSS THESE TISSUES. 586 00:26:08,270 --> 00:26:09,772 IRRESPECTIVE OF SITE AND 587 00:26:09,772 --> 00:26:13,909 SIMILARLY THE GENE EXPRESSION 588 00:26:13,909 --> 00:26:16,478 PROFILE OF VIRAL SIX IS SEEN IN 589 00:26:16,478 --> 00:26:17,880 BOTH GI AND SKIN LESIONS SO THIS 590 00:26:17,880 --> 00:26:19,882 WAS A LIMITED SAMPLE NUMBER. IT 591 00:26:19,882 --> 00:26:21,283 WAS VERY EXCITING FOR OUR GROUP 592 00:26:21,283 --> 00:26:24,453 BUT UNDERSTANDABLY WITH ALL THE 593 00:26:24,453 --> 00:26:26,622 CAVEATS OF CAPTURING SAMPLES OF 594 00:26:26,622 --> 00:26:27,423 THE TIME THAT PATIENTS PRESENT 595 00:26:27,423 --> 00:26:29,425 WE THOUGHT, WELL, THE NEXT STEP 596 00:26:29,425 --> 00:26:31,460 MAY BE TO LOOK AT ARCHIVAL 597 00:26:31,460 --> 00:26:32,561 TISSUE SO THIS IS A PROJECT THAT 598 00:26:32,561 --> 00:26:36,031 I AM VERY EXCITED ABOUT THAT HAS 599 00:26:36,031 --> 00:26:38,500 BEEN BREWING AND ONGOING AND I 600 00:26:38,500 --> 00:26:40,569 HAVE SOME PRELIMINARY RESULTS TO 601 00:26:40,569 --> 00:26:43,005 SHARE. SO WE HAVE NOW -- I'VE 602 00:26:43,005 --> 00:26:46,909 NOW BEEN LOOKING AT 43 PATIENTS 603 00:26:46,909 --> 00:26:49,712 WITH SKIN KS THAT HAVE BEEN 604 00:26:49,712 --> 00:26:52,882 SITTING IN THE LAB. AND WE HAVE 605 00:26:52,882 --> 00:26:54,783 DONE NANO STRING BECAUSE IN OF 606 00:26:54,783 --> 00:26:56,852 THESE PATIENTS, THERE'S LIMITED 607 00:26:56,852 --> 00:26:57,519 INFORMATION THAT'S ACTUALLY IN 608 00:26:57,519 --> 00:26:58,721 THE LITERATURE. 609 00:26:58,721 --> 00:27:02,658 AND SO 53 OF THESE 43 PATIENTS, 610 00:27:02,658 --> 00:27:06,061 53% OF THESE 43 PATIENTS HAVE KS 611 00:27:06,061 --> 00:27:08,931 WITH OTHER KEDS. THEY HAVE LOW 612 00:27:08,931 --> 00:27:10,432 HIV VIRAL LOADS AND VERY WELL 613 00:27:10,432 --> 00:27:13,035 CONTROLLED HIV AND LOW CD4 COUNT 614 00:27:13,035 --> 00:27:16,605 OF 175 CELLS PER MICROLITER SO 615 00:27:16,605 --> 00:27:18,440 THE INITIAL CLUSTERING OF THESE 616 00:27:18,440 --> 00:27:22,011 INITIAL HEAT MAPS OF THESE KS 617 00:27:22,011 --> 00:27:24,813 TISSUES USING NANO STRING IS 618 00:27:24,813 --> 00:27:25,948 ACTUALLY POINTING US TO SIMILAR 619 00:27:25,948 --> 00:27:29,084 PATTERNS AS WHAT WE SEE WITH THE 620 00:27:29,084 --> 00:27:31,053 BULK RNA SEQUENCING WITH 621 00:27:31,053 --> 00:27:35,057 INCREASED LEVELS POTENTIALLY OF 622 00:27:35,057 --> 00:27:39,094 SDC 1 AMONG THOSE WHO HAVE KS 623 00:27:39,094 --> 00:27:40,229 ALONE. SO VALIDATING SOME OF 624 00:27:40,229 --> 00:27:42,831 THE OBSERVATIONS THAT WE HAVE 625 00:27:42,831 --> 00:27:47,069 SEEN IN OTHER EXPERIMENTS THAT 626 00:27:47,069 --> 00:27:50,372 WE'VE DONE WITH KS IN THE CLINIC 627 00:27:50,372 --> 00:27:53,042 AND THIS BECOMES VERY IMPORTANT. 628 00:27:53,042 --> 00:27:53,809 THIS PARTICULAR PROJECT BECOMES 629 00:27:53,809 --> 00:27:57,146 IMPORTANT AS WE'RE ABLE TO 630 00:27:57,146 --> 00:27:58,514 ISOLATE THE EFFECTS OF CERTAIN 631 00:27:58,514 --> 00:28:01,216 CLINICAL FACTORS PARTICULARLY 632 00:28:01,216 --> 00:28:03,719 THE PRESENCE OF KEDS AND BECAUSE 633 00:28:03,719 --> 00:28:07,089 THIS PLATFORM ALSO INCORPORATES 634 00:28:07,089 --> 00:28:08,490 THE GENES CAN CORRELATE WHAT WE 635 00:28:08,490 --> 00:28:10,526 SEE IN THE HOST AS COMPARED TO 636 00:28:10,526 --> 00:28:15,831 EXPRESSION PROFILES OF KSHV 637 00:28:15,831 --> 00:28:17,633 GENES AND THE EFFECT ON 638 00:28:17,633 --> 00:28:20,436 LONGITUDINAL OUTCOMES. SO I 639 00:28:20,436 --> 00:28:22,338 HAVE SHOWN YOU HERE THAT BOTH 640 00:28:22,338 --> 00:28:25,975 SERUM, PBMCS AND TUMOR LESIONS 641 00:28:25,975 --> 00:28:28,377 THEMSELVES ACTUALLY GIVE US 642 00:28:28,377 --> 00:28:30,813 IMPORTANT INFORMATION THAT IS 643 00:28:30,813 --> 00:28:32,781 THROUGHOUT THE THREAD SHOWING US 644 00:28:32,781 --> 00:28:34,149 EVIDENCE OF INFLAMMATION BUT 645 00:28:34,149 --> 00:28:37,686 THERE'S ALSO EVIDENCE OF A LOT 646 00:28:37,686 --> 00:28:38,821 OF HETEROGENEITY AND THIS BRINGS 647 00:28:38,821 --> 00:28:40,723 ME TO THE BIGGER POINT THAT THIS 648 00:28:40,723 --> 00:28:42,157 IS A BIG CHALLENGE OF THE WORK 649 00:28:42,157 --> 00:28:44,426 THAT I DO IS THAT THERE IS A LOT 650 00:28:44,426 --> 00:28:46,028 OF HETEROGENEITY. AGAIN, ONE 651 00:28:46,028 --> 00:28:49,164 VIRUS GIVES US NINE DIFFERENT 652 00:28:49,164 --> 00:28:50,099 MANIFESTATIONS OF THIS DISEASE 653 00:28:50,099 --> 00:28:51,867 AND A LOT OF THIS, A LOT OF THE 654 00:28:51,867 --> 00:28:54,069 INFORMATION I PRESENTED SO FAR 655 00:28:54,069 --> 00:28:54,937 HAS BEEN FROM OUR NATURAL 656 00:28:54,937 --> 00:28:58,774 HISTORY STUDIES AT THE TIME OF 657 00:28:58,774 --> 00:29:01,443 ACTIVE DISEASE. AND THE THING 658 00:29:01,443 --> 00:29:03,779 ABOUT IT IS IT'S ALL GIVING US 659 00:29:03,779 --> 00:29:05,581 INFORMATION, CYTOKINES AT THE 660 00:29:05,581 --> 00:29:06,615 TIME OF DISEASE BUT NOT 661 00:29:06,615 --> 00:29:09,018 NECESSARILY WHAT'S DRIVING THEM. 662 00:29:09,018 --> 00:29:10,886 THE SITES THAT DRIVE SOME OF 663 00:29:10,886 --> 00:29:13,055 THESE PROCESSES TO HAPPEN. AND 664 00:29:13,055 --> 00:29:15,891 SO I WAS VERY LUCKY TO LEAD THIS 665 00:29:15,891 --> 00:29:17,760 STUDY THAT ACTUALLY SEPARATES 666 00:29:17,760 --> 00:29:20,062 PATIENT WHO IS HAVE KS AS 667 00:29:20,062 --> 00:29:22,064 COMPARED TO CURRENT KEDS FROM 668 00:29:22,064 --> 00:29:26,568 BASELINE ONWARDS IN THE STUDY OF 669 00:29:26,568 --> 00:29:30,572 LIE POE SOME MALL. SO THIS 670 00:29:30,572 --> 00:29:37,446 STUDY OF PO MA LID DO MID AND 671 00:29:37,446 --> 00:29:39,081 LIPOSOMAL DOXORUBICIN ARE BOTH 672 00:29:39,081 --> 00:29:41,483 LICENSED FOR USE IN KS. 673 00:29:41,483 --> 00:29:46,922 AND THEY WERE COMBINED IN THIS 674 00:29:46,922 --> 00:29:49,058 STUDY TO LOOK SPECIFICALLY ON 675 00:29:49,058 --> 00:29:53,062 EFFECTS OF KS ALONE AS THOSE 676 00:29:53,062 --> 00:29:56,765 COMPARED WITH OTHER KEDS SUCH AS 677 00:29:56,765 --> 00:29:58,534 CASTLEMAN'S OR KICS. THIS 678 00:29:58,534 --> 00:29:59,902 COMBINATION OF THERAPY WAS GIVEN 679 00:29:59,902 --> 00:30:02,304 UNTIL THERE WAS A RESPONSE IN 680 00:30:02,304 --> 00:30:03,539 KS. 681 00:30:03,539 --> 00:30:04,973 UNTIL PROGRESSION OR UNTIL AS 682 00:30:04,973 --> 00:30:08,077 THE PI, WE DETERMINE THAT THE 683 00:30:08,077 --> 00:30:11,246 PATIENT COULD NO LONGER 684 00:30:11,246 --> 00:30:14,416 PARTICIPATE. SO TO ILLUSTRATE 685 00:30:14,416 --> 00:30:15,451 WHAT HAPPENS IN A CLINICAL TRIAL 686 00:30:15,451 --> 00:30:19,188 WHAT WE DO, I WANTED TO TAKE YOU 687 00:30:19,188 --> 00:30:21,223 THROUGH TO CASES, TWO CASES THAT 688 00:30:21,223 --> 00:30:23,025 WERE PART OF THESE GROUPS SO 689 00:30:23,025 --> 00:30:23,926 PATIENT NUMBER ONE AS WE'LL 690 00:30:23,926 --> 00:30:27,029 REFER TO HIM WAS A -- IN GROUP 691 00:30:27,029 --> 00:30:30,833 ONE WHO HAD KS ALONE WAS A 692 00:30:30,833 --> 00:30:32,835 42-YEAR-OLD CAN IS SENDERED MAN 693 00:30:32,835 --> 00:30:33,702 WORKING IN FASHION. 694 00:30:33,702 --> 00:30:35,537 HE WAS DIAGNOSED WITH HIV IN 695 00:30:35,537 --> 00:30:40,676 OCTOBER OF 2018 AND PROTECT -- 696 00:30:40,676 --> 00:30:43,245 PRESENTED IN KS ON HIS SKIN AND 697 00:30:43,245 --> 00:30:45,080 LUNGS AND HAD OPPORTUNISTIC 698 00:30:45,080 --> 00:30:46,515 INFECTIONS WHEN WE FIRST MET HIM 699 00:30:46,515 --> 00:30:50,853 BUT HE HAD NO OTHER EVIDENCE OF 700 00:30:50,853 --> 00:30:52,421 KICS OF MCD. 701 00:30:52,421 --> 00:30:55,090 THIS IS HOW HIS KS LOOKED AT THE 702 00:30:55,090 --> 00:30:57,059 TIME HE ENROLLED AND AS YOU CAN 703 00:30:57,059 --> 00:31:00,963 SEE HERE ON THE CT SCAN EVIDENCE 704 00:31:00,963 --> 00:31:03,065 OF INFILTRATES SHOWING HIS KS SO 705 00:31:03,065 --> 00:31:06,101 IN TERMS OF OUR VENN DIAGRAM OF 706 00:31:06,101 --> 00:31:09,938 COMBINATIONS HE SITS IN KS 707 00:31:09,938 --> 00:31:11,073 ALONE. COMPARE THAT WITH 708 00:31:11,073 --> 00:31:13,142 PARTICIPANT -- PATIENT TWO WHO 709 00:31:13,142 --> 00:31:15,911 WAS IN GROUP TWO, WHO HAD KS 710 00:31:15,911 --> 00:31:19,281 WITH KICS. HE WAS A 52-YEAR-OLD 711 00:31:19,281 --> 00:31:21,917 CHRIS GENDERED MAN WHO WAS 712 00:31:21,917 --> 00:31:24,586 STUDYING FOR A PH.D. MANY 713 00:31:24,586 --> 00:31:25,721 MANAGEMENT. 714 00:31:25,721 --> 00:31:27,623 HE WAS DIAGNOSED WITH HIV IN 715 00:31:27,623 --> 00:31:30,692 2019 AND PROTECTS WITH SKIN KS, 716 00:31:30,692 --> 00:31:34,897 KS IN HIS ORAL MUCOSA AND GI KS. 717 00:31:34,897 --> 00:31:37,633 AGAIN, BOTH PATIENTS HAVE STAGE 718 00:31:37,633 --> 00:31:41,303 ONE KS. AND HE HAS EVIDENCE OF 719 00:31:41,303 --> 00:31:44,907 KICS. AND WE'LL TALK ABOUT THAT 720 00:31:44,907 --> 00:31:47,142 IN THE NEXT SLIDE BUT THESE ARE 721 00:31:47,142 --> 00:31:49,278 IMAGES OF PATIENTS WE ARE SEEING 722 00:31:49,278 --> 00:31:51,847 IN THE CLINIC MOST OFTEN ON A 723 00:31:51,847 --> 00:31:53,582 WEDNESDAY. SO YOU CAN SEE 724 00:31:53,582 --> 00:31:56,718 EVIDENCE OF KS IN THIS GENTLEMAN 725 00:31:56,718 --> 00:31:59,388 BOTH IN THE ORAL MEW KOE SASHGS 726 00:31:59,388 --> 00:32:03,091 THE EYES AS WELL AS IN THE GI 727 00:32:03,091 --> 00:32:05,894 TRACT. IN TERMS OF THE -- OF 728 00:32:05,894 --> 00:32:07,029 WHERE THIS PARTICIPANT SITS IN 729 00:32:07,029 --> 00:32:09,431 OUR VENN DIAGRAM HE SITS AS 730 00:32:09,431 --> 00:32:12,000 SOMEONE WHO HAS KS AND KICS. 731 00:32:12,000 --> 00:32:13,435 SO WE DID ADDITIONAL WORKUP IN 732 00:32:13,435 --> 00:32:14,636 THIS PATIENT, AGAIN, TO MAKE 733 00:32:14,636 --> 00:32:17,439 SURE THAT HE DID NOT HAVE 734 00:32:17,439 --> 00:32:19,374 CASTLEMAN'S OR PEL AND WE SEE 735 00:32:19,374 --> 00:32:21,276 THAT HE HAD AN ADDITIONAL BIOPSY 736 00:32:21,276 --> 00:32:23,745 OF A LYMPH NODE THAT ALSO SHOWED 737 00:32:23,745 --> 00:32:24,313 KS. 738 00:32:24,313 --> 00:32:26,315 AND AS YOU CAN SEE ON THE SCREEN 739 00:32:26,315 --> 00:32:31,119 HE DID HAVE ELEVATED KSHV VIRAL 740 00:32:31,119 --> 00:32:36,024 LOAD OF OVER 4,000 COPIES IN HIS 741 00:32:36,024 --> 00:32:38,227 CIRCULATION. CLEARLY WE 742 00:32:38,227 --> 00:32:38,860 ESTABLISHED HIS DIAGNOSIS OF 743 00:32:38,860 --> 00:32:41,396 KICS AND HE STARTS THE PROTOCOL 744 00:32:41,396 --> 00:32:47,369 TO TREAT BOTH HIS KICS AND KS. 745 00:32:47,369 --> 00:32:49,771 PARTICIPANT NUMBER ONE HAS -- AN 746 00:32:49,771 --> 00:32:50,872 EXCELLENT PARTIAL RESPONSE IN 747 00:32:50,872 --> 00:32:53,842 HIS KS HE RECEIVES EIGHT CYCLES 748 00:32:53,842 --> 00:33:00,949 OF THERAPY PE HE GETS SOME DOSE 749 00:33:00,949 --> 00:33:01,250 REDUCTION. 750 00:33:01,250 --> 00:33:05,087 AND HAS THE CELLS TO LOW TO 751 00:33:05,087 --> 00:33:06,722 SLIGHTLY ABOVE THAT. HIS 752 00:33:06,722 --> 00:33:09,258 RESPONSE MIMICS WHAT WE SEE 753 00:33:09,258 --> 00:33:10,892 AMONG A LOT OF THE PARTICIPANTS 754 00:33:10,892 --> 00:33:13,228 WHERE WE SAW 79% RESPONSE RATE 755 00:33:13,228 --> 00:33:18,333 WITH THE COMBINATION OF PA MA 756 00:33:18,333 --> 00:33:20,335 LID DA MID. WHEREAS PARTICIPANT 757 00:33:20,335 --> 00:33:23,505 TWO HAS A VERY DIFFERENT COURSE 758 00:33:23,505 --> 00:33:25,307 IN GROUP TWO, ALTHOUGH HE HAS A 759 00:33:25,307 --> 00:33:27,976 PARTIAL RESPONSE IN HIS KS AND 760 00:33:27,976 --> 00:33:30,746 HIS KICS RESPONSE, HE CONTINUES 761 00:33:30,746 --> 00:33:34,182 TO HAVE SYMPTOMS THAT WORSEN IN 762 00:33:34,182 --> 00:33:35,083 JANUARY. 763 00:33:35,083 --> 00:33:37,352 HE STOPS HIS THERAPY, AN 764 00:33:37,352 --> 00:33:39,087 ADDITIONAL WORKUP IDENTIFIES 765 00:33:39,087 --> 00:33:41,590 THAT HE HAS PRIMARY EFFUSION 766 00:33:41,590 --> 00:33:43,425 LYMPHOMA. HE INITIATES 767 00:33:43,425 --> 00:33:44,960 TREATMENT AT THE TIME BUT 768 00:33:44,960 --> 00:33:47,863 UNFORTUNATELY BY MAY OF 2020 HE 769 00:33:47,863 --> 00:33:51,199 DIES OF HIS LYMPHOMA. SO 770 00:33:51,199 --> 00:33:53,869 CLEARLY WE HAVE A STUDY WHERE 771 00:33:53,869 --> 00:33:57,005 TWO PATIENTS HAVE HIV AND KS AND 772 00:33:57,005 --> 00:33:59,074 PRESENT VERY SIMILARLY. ONE 773 00:33:59,074 --> 00:34:01,576 OBVIOUSLY WITH KICS AND THE 774 00:34:01,576 --> 00:34:03,178 OTHER ONE DOESN'T. AND WHAT WE 775 00:34:03,178 --> 00:34:04,946 SEE ON THIS GRAPH IS THAT THE 776 00:34:04,946 --> 00:34:07,082 RESPONSE RATES ARE DIFFERENT IN 777 00:34:07,082 --> 00:34:10,218 THIS STUDY BY THEIR DIAGNOSES. 778 00:34:10,218 --> 00:34:13,155 SO THIS OFFERS US AN OPPORTUNITY 779 00:34:13,155 --> 00:34:15,524 TO BETTER UNDERSTAND KEDS AS 780 00:34:15,524 --> 00:34:18,660 THEY OCCUR IN KS IN THIS STUDY. 781 00:34:18,660 --> 00:34:20,896 AND SO AS I APPROACH THIS, I 782 00:34:20,896 --> 00:34:22,898 STARTED TO THINK, WELL, HOW CAN 783 00:34:22,898 --> 00:34:24,966 WE USE THE CORRELATIVE SAMPLES 784 00:34:24,966 --> 00:34:27,202 IN THE STUDY TO BETTER 785 00:34:27,202 --> 00:34:29,271 UNDERSTAND AND DELINEATE THESE 786 00:34:29,271 --> 00:34:31,707 DISEASES AS THEY OCCUR. I 787 00:34:31,707 --> 00:34:32,974 IDENTIFIED A GROUP OF PATIENTS 788 00:34:32,974 --> 00:34:35,077 BOTH IN GROUP ONE AND TWO. WHO 789 00:34:35,077 --> 00:34:38,747 WERE ADJUSTED FOR THEIR BASELINE 790 00:34:38,747 --> 00:34:43,585 CHARACTERISTICS SUCH AS AGE, CD4 791 00:34:43,585 --> 00:34:46,822 T-CELLS, OBTAINED SERUM AT 792 00:34:46,822 --> 00:34:49,858 BASELINE AND WE DID A THOROUGH 793 00:34:49,858 --> 00:34:53,328 SYSTEMATIC APPROACH OF LOOKING 794 00:34:53,328 --> 00:34:56,598 AT OMICS IN THESE PARTICIPANTS. 795 00:34:56,598 --> 00:34:59,334 SO A SCAN WHICH IDENTIFIES 7,000 796 00:34:59,334 --> 00:35:01,103 PROTEINS AS WELL AS BULK RNA 797 00:35:01,103 --> 00:35:03,004 SEQUENCING IN THE CIRCULATION 798 00:35:03,004 --> 00:35:05,607 AND FLOW CYTOMETRY. THUS, BEING 799 00:35:05,607 --> 00:35:08,910 ABLE TO CATEGORIZE AT BASELINE 800 00:35:08,910 --> 00:35:12,881 THESE TWO DISEASE PROCESSES IN 801 00:35:12,881 --> 00:35:17,652 GROUP ONE VERSUS GROUP TWO. AND 802 00:35:17,652 --> 00:35:19,121 FROM THE INITIAL FORAY INTO 803 00:35:19,121 --> 00:35:22,591 THESE RESULTS WE IDENTIFY THAT 804 00:35:22,591 --> 00:35:24,025 THOSE WHO WERE IN -- BETWEEN 805 00:35:24,025 --> 00:35:26,461 GROUP ONE AND GROUP TWO, GROUP 806 00:35:26,461 --> 00:35:28,463 ONE BEING THE GREEN AND GROUP 807 00:35:28,463 --> 00:35:33,034 TWO BEING THE RED WE SEE SOME 808 00:35:33,034 --> 00:35:35,404 SIGNIFICANT DIFFERENCES IN THE 809 00:35:35,404 --> 00:35:37,973 IL-6 SIGNALLING. WE SEE THAT 810 00:35:37,973 --> 00:35:40,609 THERE'S A SEPARATION AND THIS IS 811 00:35:40,609 --> 00:35:42,511 PARTICULARLY IMPORTANT FOR TWO 812 00:35:42,511 --> 00:35:46,481 REASONS, THE FIRST IS THAT THE 813 00:35:46,481 --> 00:35:49,985 HIGHLIGHTED PROTEINS IL-6 AND 814 00:35:49,985 --> 00:35:52,554 CSF 1 SUPPORT THE USE OF PROCRIT 815 00:35:52,554 --> 00:35:56,091 ANYBODY WHICH IS A STUDY THAT 816 00:35:56,091 --> 00:35:58,627 WE'RE LAUNCHING THAT HAS 817 00:35:58,627 --> 00:36:06,168 PATIENTS WHO HAVE KICS WITH KS 818 00:36:06,168 --> 00:36:08,904 OR CASTLEMAN'S WITH KS JOINING 819 00:36:08,904 --> 00:36:14,209 IN THIS TRIAL AND THIS IS A CSF 820 00:36:14,209 --> 00:36:19,080 R1 INHIBITOR THAT IS LICENSED 821 00:36:19,080 --> 00:36:20,749 FOR FIBROSIS AND THIS MAY BYPASS 822 00:36:20,749 --> 00:36:22,784 SOME OF THE ISSUES WE SAW WITH 823 00:36:22,784 --> 00:36:27,489 IL-6 JUST IL-6 INHIBITION ITSELF 824 00:36:27,489 --> 00:36:28,723 BY SPECIFICALLY ADDRESSING MOST 825 00:36:28,723 --> 00:36:31,059 OF THE DOWNSTREAM EFFECTS OF -- 826 00:36:31,059 --> 00:36:35,931 UPSTREAM EFFECTS OF IL-6 AND THE 827 00:36:35,931 --> 00:36:38,800 SECOND REASON WHY THIS PROTEOMIC 828 00:36:38,800 --> 00:36:40,769 ANALYSIS IS IMPORTANT IS IT 829 00:36:40,769 --> 00:36:42,838 HELPS US GET A SET OF DATA AND 830 00:36:42,838 --> 00:36:46,575 PROTEINS THAT MAY BE USED FOR 831 00:36:46,575 --> 00:36:48,477 DIAGNOSIS OF PATIENTS BETWEEN KS 832 00:36:48,477 --> 00:36:50,979 AND KS CAN OTHER KEDS THAT WE 833 00:36:50,979 --> 00:36:55,016 PLAN TO VALIDATE IN LARGER 834 00:36:55,016 --> 00:36:55,350 POPULATIONS. 835 00:36:55,350 --> 00:36:58,353 AND WITH THIS IN MIND, WE'RE 836 00:36:58,353 --> 00:37:00,922 ALSO EXCITED TO SEE THAT 837 00:37:00,922 --> 00:37:02,157 COMPARING GROUP ONE VERSUS TWO, 838 00:37:02,157 --> 00:37:04,826 WE'VE STARTED TO SEE THAT THE 839 00:37:04,826 --> 00:37:06,228 BULK RNA SEQUENCING AND 840 00:37:06,228 --> 00:37:09,064 PROTEOMIC PATHWAYS ARE CLEARLY 841 00:37:09,064 --> 00:37:11,066 HIGHER IN GROUP TWO, AGAIN, 842 00:37:11,066 --> 00:37:12,234 SUPPORTING OUR UNDERSTANDING 843 00:37:12,234 --> 00:37:15,704 THAT THIS IS A PROINFLAMMATORY 844 00:37:15,704 --> 00:37:19,074 CONDITION. FINALLY, THINKING 845 00:37:19,074 --> 00:37:21,843 ABOUT THE FLOW CYTOMETRY RESULTS 846 00:37:21,843 --> 00:37:23,245 FROM THESE ANALYSES OF PATIENTS 847 00:37:23,245 --> 00:37:26,248 ON THE STUDY, WE SEE THAT AS WE 848 00:37:26,248 --> 00:37:29,918 EXPECTED FROM OUR INFLAMMASOME 849 00:37:29,918 --> 00:37:32,521 WORK, ELEVATED INTERMEDIATE 850 00:37:32,521 --> 00:37:35,290 MONOCYTES IN THOSE WITH MCD, 851 00:37:35,290 --> 00:37:37,926 KICS, AND KS COMPARED TO KS 852 00:37:37,926 --> 00:37:40,295 ALONE. WE ALSO SEE ACTIVATED 853 00:37:40,295 --> 00:37:43,798 T-CELL PROFILES IN THOSE WITH KS 854 00:37:43,798 --> 00:37:47,669 AND OTHER KEDS. AND THIS IS 855 00:37:47,669 --> 00:37:48,570 INTERESTING BECAUSE WE'VE SEEN 856 00:37:48,570 --> 00:37:50,539 SOME OF THESE ACTIVATED T-CELLS 857 00:37:50,539 --> 00:37:53,141 ARE ALSO INCREASED IN PATIENTS 858 00:37:53,141 --> 00:37:58,146 WITH COVID AND ARE OFTEN 859 00:37:58,146 --> 00:37:58,847 ASSOCIATED WITH SEVERITY OF 860 00:37:58,847 --> 00:38:02,484 COVID. AND THAT TAKES US TO THE 861 00:38:02,484 --> 00:38:04,519 NEXT STEP WHICH IS REALLY 862 00:38:04,519 --> 00:38:06,688 DELVING INTO THE EFFECTS OF THE 863 00:38:06,688 --> 00:38:10,025 VIRUS ITSELF, KSHV AND HOW THIS 864 00:38:10,025 --> 00:38:11,059 INFLUENCES SOME OF THE THINGS 865 00:38:11,059 --> 00:38:13,728 WE'RE SEEING BOTH IN THE 866 00:38:13,728 --> 00:38:16,631 PROTEIN, THE RNA SEQUENCING AS 867 00:38:16,631 --> 00:38:18,633 WELL AS THE FLOW CYTOMETRY 868 00:38:18,633 --> 00:38:22,037 RESULTS AND SO TOGETHER WE'RE 869 00:38:22,037 --> 00:38:24,673 ABLE TO BUILD A COMPREHENSIVE 870 00:38:24,673 --> 00:38:26,841 PROFILE THAT HELPS DELINEATE 871 00:38:26,841 --> 00:38:28,810 PATIENTS WHO HAVE KS ALONE 872 00:38:28,810 --> 00:38:30,612 VERSUS THOSE WHO HAVE KS WITH 873 00:38:30,612 --> 00:38:34,983 OTHER KEDS, THUS SUPPORTING THE 874 00:38:34,983 --> 00:38:39,588 PLAN TO DEVELOP NEW DIAGNOSTICS 875 00:38:39,588 --> 00:38:43,124 FOR THESE DISEASES. SO LOOKING 876 00:38:43,124 --> 00:38:46,394 TO THE FUTURE, I HAVE LEARNED A 877 00:38:46,394 --> 00:38:50,565 LOT IN MY JOURNEY SO FAR TO TRY 878 00:38:50,565 --> 00:38:52,767 TO DELINEATE THESE DISORDERS AND 879 00:38:52,767 --> 00:38:54,603 WITH THE PLAN I HAVE FOR ONGOING 880 00:38:54,603 --> 00:38:57,706 CLINICAL TRIALS I AIM TO 881 00:38:57,706 --> 00:39:00,909 INCORPORATE WHAT I LEARNED BY 882 00:39:00,909 --> 00:39:02,010 COLLECTING SYSTEMICALLY BLOOD 883 00:39:02,010 --> 00:39:03,778 AND TISSUE OVER TIME POINTS FOR 884 00:39:03,778 --> 00:39:05,480 THE STUDIES THAT I'M RUNNING: I 885 00:39:05,480 --> 00:39:07,082 HAVE LISTED THEM ON THE SCREEN 886 00:39:07,082 --> 00:39:10,418 HERE BUT THEY INCLUDE STUDIES OF 887 00:39:10,418 --> 00:39:16,925 A CDK 46 INHIBITOR AND KS. A 888 00:39:16,925 --> 00:39:19,294 CYTOKINES INCLUDING IL-12 AND 7 889 00:39:19,294 --> 00:39:22,197 IN KS AS WELL AS THE STUDY I 890 00:39:22,197 --> 00:39:25,767 MENTIONED. AND IN DOING SO I 891 00:39:25,767 --> 00:39:30,305 HOPE TO CREATE A BETTER 892 00:39:30,305 --> 00:39:32,007 UNDERSTANDING OF THE VIRUS, THE 893 00:39:32,007 --> 00:39:33,274 INTERACTION, THE IMMUNE SYSTEM, 894 00:39:33,274 --> 00:39:35,443 AND THE EFFECTS OF THE TREATMENT 895 00:39:35,443 --> 00:39:39,080 OF THESE DISORDERS. AND SO, 896 00:39:39,080 --> 00:39:42,150 WITH THAT, I THANK YOU, AGAIN, 897 00:39:42,150 --> 00:39:44,152 FOR THE OPPORTUNITY TO CHAT WITH 898 00:39:44,152 --> 00:39:45,954 YOU TODAY AND IT'S IMPORTANT 899 00:39:45,954 --> 00:39:50,859 THAT I THANK MY WONDERFUL BRANCH 900 00:39:50,859 --> 00:39:56,898 WHO ARE HERE. DR. LORRAINE, 901 00:39:56,898 --> 00:39:59,401 FUTURE DOCTOR. THE CREW LAB. 902 00:39:59,401 --> 00:40:02,971 OUR MANY, MANY RESEARCHERS AND 903 00:40:02,971 --> 00:40:07,542 MANY OF WHOM ARE LISTENING, MY 904 00:40:07,542 --> 00:40:09,144 MENTORSHIP COMMITTEE. OUR 905 00:40:09,144 --> 00:40:10,779 COLLABORATORS AND OUR PATIENTS 906 00:40:10,779 --> 00:40:14,115 WHO ARE THE MOST IMPORTANT THING 907 00:40:14,115 --> 00:40:17,686 AND THE REASON MANY OF US GET UP 908 00:40:17,686 --> 00:40:20,955 IN THE MORNING SO THANK YOU VERY 909 00:40:20,955 --> 00:40:27,062 MUCH FOR YOUR TIME. 910 00:40:27,062 --> 00:40:31,066 >> AUDIENCE: (APPLAUSE). 911 00:40:31,066 --> 00:40:38,239 >> ANY QUESTIONS. 912 00:40:38,239 --> 00:40:40,108 >> AUDIENCE: GREAT TO SEE YOU. 913 00:40:40,108 --> 00:40:43,745 FANTASTIC TALK AS ALWAYS. I'VE 914 00:40:43,745 --> 00:40:44,946 PROBABLY ASKED THIS QUESTION IN 915 00:40:44,946 --> 00:40:46,047 DIFFERENT WAYS BEFORE. THE 916 00:40:46,047 --> 00:40:47,615 PATIENT, THE LAST PATIENT YOU 917 00:40:47,615 --> 00:40:49,784 PRESENTED WHO, YOU KNOW, COMES 918 00:40:49,784 --> 00:40:54,089 IN WITH KS AND KICS AND HAS 919 00:40:54,089 --> 00:41:01,196 UNCONTROLLED INFLAMMATION AND 920 00:41:01,196 --> 00:41:05,934 THEN HAS PEL. AT WHAT STAGE DO 921 00:41:05,934 --> 00:41:07,469 YOU THINK HE HAS P EL. I KNOW 922 00:41:07,469 --> 00:41:09,471 IT'S IMPOSSIBLE TO SAY. DO YOU 923 00:41:09,471 --> 00:41:11,139 THINK IT'S A GENE THAT SETS THIS 924 00:41:11,139 --> 00:41:15,076 OFF OR IS IT THE UNCONTROLLED 925 00:41:15,076 --> 00:41:15,777 INFLAMMATORY RESPONSE WITH THIS 926 00:41:15,777 --> 00:41:19,914 REPLICATION OF INFLAMMATORY 927 00:41:19,914 --> 00:41:23,084 STIMULI CAUSED THIS TO EVOLVE. 928 00:41:23,084 --> 00:41:25,253 DO WE HAVE HYPOTHESES ON THAT? 929 00:41:25,253 --> 00:41:27,055 >> THANK YOU, JOE, GOOD TO SEE 930 00:41:27,055 --> 00:41:29,891 YOU TOO. SO THERE'S A COHORT OF 931 00:41:29,891 --> 00:41:31,426 OUR PATIENTS WHO HAVE 932 00:41:31,426 --> 00:41:32,861 CASTLEMAN'S WHO THEN GO TO 933 00:41:32,861 --> 00:41:35,063 HAVING PEL AND I THINK THAT 934 00:41:35,063 --> 00:41:35,864 GROUP OF PATIENTS ARE PROBABLY 935 00:41:35,864 --> 00:41:40,168 THE BEST GROUP TO ANSWER YOUR 936 00:41:40,168 --> 00:41:40,769 QUESTION. PARTICULARLY TO 937 00:41:40,769 --> 00:41:42,370 UNDERSTAND WHY THESE CELLS THAT 938 00:41:42,370 --> 00:41:46,074 ARE POLYCLONAL THEN GO INTO A 939 00:41:46,074 --> 00:41:48,476 MONOCLONAL B-CELL PROCESS. I 940 00:41:48,476 --> 00:41:49,778 GET THE -- IT'S PROBABLY 941 00:41:49,778 --> 00:41:51,913 COMBINATION OF THINGS AND THAT 942 00:41:51,913 --> 00:41:53,782 THERE IS SOME SORT OF VIRAL 943 00:41:53,782 --> 00:41:55,583 COMPONENT THAT DRIVE THOSE 944 00:41:55,583 --> 00:41:57,886 B-CELLS TO GO FROM A POLYCLONAL 945 00:41:57,886 --> 00:42:00,088 PROCESS TO A MONOCLONAL PROCESS. 946 00:42:00,088 --> 00:42:03,591 THAT BEING SAID, WE -- WE ARE 947 00:42:03,591 --> 00:42:04,926 UNDERSTANDING KICS AS AN ENTITY 948 00:42:04,926 --> 00:42:08,797 MORE AND MORE OVER TIME. THE 949 00:42:08,797 --> 00:42:11,065 INITIAL REPORTS OF KICS INCLUDED 950 00:42:11,065 --> 00:42:13,301 PATIENTS WITH PEL AND WE'RE 951 00:42:13,301 --> 00:42:16,070 SEEING MORE AND MORE THAT PEL IS 952 00:42:16,070 --> 00:42:18,840 A DISTINCT ENTITY AND AS YOU 953 00:42:18,840 --> 00:42:20,575 STUDY HLH AS WELL THESE ARE 954 00:42:20,575 --> 00:42:23,011 PATIENTS WITH MORE OF THE HLH 955 00:42:23,011 --> 00:42:24,479 PHENOTYPE AS COMPARED TO THOSE 956 00:42:24,479 --> 00:42:26,548 WITH KICS. SO TO YOUR QUESTION 957 00:42:26,548 --> 00:42:30,652 I THINK THAT A LOT OF THESE 958 00:42:30,652 --> 00:42:32,720 PATIENTS HAVE PEL SITTING AROUND 959 00:42:32,720 --> 00:42:38,793 BUT THE DIAGNOSTIC POSSROCESSESE 960 00:42:38,793 --> 00:42:40,361 SO CHALLENGING IN THESE PATIENTS 961 00:42:40,361 --> 00:42:42,931 AND THERE ARE SO FEW CELLS THAT 962 00:42:42,931 --> 00:42:44,265 THAT ITSELF PRESENTS THE 963 00:42:44,265 --> 00:42:45,867 ADDITIONAL ROADBLOCK. 964 00:42:45,867 --> 00:42:46,434 >> AUDIENCE: ONE FOLLOW UP 965 00:42:46,434 --> 00:42:49,637 QUESTION IF I COULD ASK IT. SO 966 00:42:49,637 --> 00:42:51,940 WITH THE PA CAT ANYBODY WHICH I 967 00:42:51,940 --> 00:42:53,441 THINK IS FANTASTIC AND REALLY 968 00:42:53,441 --> 00:42:54,709 LOOKING FORWARD TO SEEING WHAT 969 00:42:54,709 --> 00:42:56,411 YOU FIND ARE THERE ANY CONCERNS, 970 00:42:56,411 --> 00:42:58,546 I LOVE GIVING IMMUNOSUPPRESSION 971 00:42:58,546 --> 00:43:00,348 WITH PEOPLE WITH INFECTIONS BUT 972 00:43:00,348 --> 00:43:02,984 ANY CONCERNS WITH THE INHIBITOR 973 00:43:02,984 --> 00:43:04,652 SPECIFICALLY AND VIRUSES BECOME 974 00:43:04,652 --> 00:43:07,722 A PROBLEM WITH KSHV BECOMING A 975 00:43:07,722 --> 00:43:11,059 BIT MORE UNCONTROLLED WITH THAT? 976 00:43:11,059 --> 00:43:13,294 >> THIS IS A VERY SPECIFICALLY 977 00:43:13,294 --> 00:43:14,462 TARGETED INHIBITOR AS COMPARED 978 00:43:14,462 --> 00:43:17,131 TO OTHERS ON THE MARKET. SO WE 979 00:43:17,131 --> 00:43:19,500 WILL BE KEEPING A VERY CLOSE 980 00:43:19,500 --> 00:43:22,103 MONITORING ON OPPORTUNISTIC 981 00:43:22,103 --> 00:43:24,372 INFECTIONS. THANKS WITH THE 982 00:43:24,372 --> 00:43:26,841 HELP OF OUR NYAD COLLEAGUES AS 983 00:43:26,841 --> 00:43:27,075 WELL. 984 00:43:27,075 --> 00:43:30,879 >> AUDIENCE: FANTASTIC. 985 00:43:30,879 --> 00:43:35,650 >> THANK YOU. OKAY. I THINK 986 00:43:35,650 --> 00:43:37,452 WE'RE GOOD. ALL RIGHT, THANK 987 00:43:37,452 --> 00:43:41,322 YOU SO MUCH. OH -- WAS THERE A 988 00:43:41,322 --> 00:43:45,627 QUESTI 989 00:43:45,627 --> 00:43:45,894 QUESTION? 990 00:43:45,894 --> 00:43:47,962 >> AUDIENCE: GREAT TALK. IS THE 991 00:43:47,962 --> 00:43:50,832 INCIDENCE OF KICS OR KS 992 00:43:50,832 --> 00:43:52,267 DEPENDENT ON THE PARTICULAR 993 00:43:52,267 --> 00:43:54,869 SUBTYPE OF HIV INFECTION IN IS 994 00:43:54,869 --> 00:43:55,470 THERE ANY RELATIONSHIP TO THE 995 00:43:55,470 --> 00:43:57,538 (SPEAKER FAR FROM MIC). 996 00:43:57,538 --> 00:44:00,041 >> I DON'T THINK IT IS. I DON'T 997 00:44:00,041 --> 00:44:01,609 THINK WE SEE THAT AS MUCH BUT 998 00:44:01,609 --> 00:44:04,178 THAT'S A GOOD THOUGHT. WE -- I 999 00:44:04,178 --> 00:44:04,879 DON'T THINK WE'VE LOOKED IN 1000 00:44:04,879 --> 00:44:06,514 DETAIL BUT IT IS A GOOD THOUGHT 1001 00:44:06,514 --> 00:44:09,450 AND I DON'T THINK IT IS BUT WE 1002 00:44:09,450 --> 00:44:10,518 SHOULD LOOK. THANK YOU. ALL 1003 00:44:10,518 --> 00:44:13,221 RIGHT. OKAY, I THINK WE'RE NOW 1004 00:44:13,221 --> 00:44:13,621 DONE. THANK YOU. 1005 00:44:13,621 --> 00:44:24,065 >> AUDIENCE: (APPLAUSE).