1 00:00:05,360 --> 00:00:08,200 >> WELCOME TO 2 00:00:08,200 --> 00:00:09,360 EVERYONE TO THE SECOND DAY OF 3 00:00:09,360 --> 00:00:12,440 THE WORKSHOP ON LYMPHATIC SYSTEM 4 00:00:12,440 --> 00:00:13,360 IN HEALTH AND DISEASE. 5 00:00:13,360 --> 00:00:15,320 YESTERDAY WE HAD A SUCCESSFUL 6 00:00:15,320 --> 00:00:17,920 DAY FOCUSING ON LYMPHATIC 7 00:00:17,920 --> 00:00:18,960 DEVELOPMENT FUNCTION AND SOME OF 8 00:00:18,960 --> 00:00:21,080 THE DISEASE CONDITIONS AND TODAY 9 00:00:21,080 --> 00:00:22,880 WE WILL CONTINUE ANOTHER 10 00:00:22,880 --> 00:00:25,040 GREAT -- ANOTHER DAY OF GREAT 11 00:00:25,040 --> 00:00:27,760 TALKS LINED UP FOR LYMPHATIC 12 00:00:27,760 --> 00:00:28,640 DISEASES, COMMUNITIES 13 00:00:28,640 --> 00:00:29,800 PERSPECTIVE AND NEW TECHNOLOGIES 14 00:00:29,800 --> 00:00:31,080 IN IMAGING AND MAPPING. 15 00:00:31,080 --> 00:00:33,480 LET ME REMIND YOU OUR 16 00:00:33,480 --> 00:00:34,400 HOUSEKEEPING ANNOUNCEMENTS, IF 17 00:00:34,400 --> 00:00:35,560 YOU'RE ONLY JOINING TODAY. 18 00:00:35,560 --> 00:00:37,720 THIS WORKSHOP IS RECORDED AND 19 00:00:37,720 --> 00:00:39,480 WILL BE AVAILABLE FOR EVERYONE 20 00:00:39,480 --> 00:00:42,440 IN PERPETUITY IN NIH VIDEOCAST 21 00:00:42,440 --> 00:00:42,800 COLLECTION. 22 00:00:42,800 --> 00:00:44,960 THE LINKS FOR THE VIDEOCAST 23 00:00:44,960 --> 00:00:46,840 RECORDING ALONG WITH THE 24 00:00:46,840 --> 00:00:48,640 DETAILED INFORMATION OF ALL 25 00:00:48,640 --> 00:00:50,200 SPEAKERS CAN BE FOUND ON THE 26 00:00:50,200 --> 00:00:50,880 REGISTRATION PAGE. 27 00:00:50,880 --> 00:00:54,120 ALL THESE LINKS ARE POSTED. 28 00:00:54,120 --> 00:00:54,320 ALSO 29 00:00:54,320 --> 00:00:55,560 IN THE CHAT AND WILL BE 30 00:00:55,560 --> 00:00:56,880 AVAILABLE TO EVERYONE AFTER THE 31 00:00:56,880 --> 00:00:58,200 WORKSHOP AS WELL. 32 00:00:58,200 --> 00:00:59,920 THE SPEAKERS WILL PRESENT THEIR 33 00:00:59,920 --> 00:01:01,920 TALKS AND THEY WILL ANSWER THE 34 00:01:01,920 --> 00:01:03,960 QUESTIONS AS A PANEL AT THE END 35 00:01:03,960 --> 00:01:05,520 OF EVERY SESSION, AND WHICH WILL 36 00:01:05,520 --> 00:01:08,680 BE LED BY THE SESSION MODERATOR. 37 00:01:08,680 --> 00:01:11,640 PLEASE SUBMIT YOUR QUESTIONS, 38 00:01:11,640 --> 00:01:13,400 OUR ZOOM ATTENDEES PLEASE PUT IT 39 00:01:13,400 --> 00:01:15,600 IN Q & A AND VIDEOCAST WITH THE 40 00:01:15,600 --> 00:01:18,440 LIVE FEEDBACK FUNCTION, AND WE 41 00:01:18,440 --> 00:01:20,080 WILL GIVE TO THE MODERATOR. 42 00:01:20,080 --> 00:01:22,360 THE MODERATORS WILL BE READING 43 00:01:22,360 --> 00:01:23,440 AND DIRECTING YOUR QUESTIONS TO 44 00:01:23,440 --> 00:01:25,440 THE PANELISTS. 45 00:01:25,440 --> 00:01:28,160 WE REQUEST OUR SPEAKERS TO RAISE 46 00:01:28,160 --> 00:01:29,280 HAND, UNMUTE AND ASK THEIR 47 00:01:29,280 --> 00:01:30,480 QUESTIONS LIVE. 48 00:01:30,480 --> 00:01:33,080 TO START THE DAY, IT IS MY 49 00:01:33,080 --> 00:01:35,280 DISTINCT PLEASURE TO INTRODUCE 50 00:01:35,280 --> 00:01:36,960 DR. DAVID GOFF, DIRECTOR OF 51 00:01:36,960 --> 00:01:39,560 DIVISION OF CARDIOVASCULAR 52 00:01:39,560 --> 00:01:41,800 DISEASES IN NHLBI, AND DR. GOFF 53 00:01:41,800 --> 00:01:43,360 WILL BE GIVING THE WELCOME 54 00:01:43,360 --> 00:01:46,200 REMARKS FOR THE DAY TWO. 55 00:01:46,200 --> 00:01:46,840 DR. GOFF? 56 00:01:46,840 --> 00:01:48,720 >> THANK YOU, SELEN. 57 00:01:48,720 --> 00:01:53,240 I WANT TO THANK EVERYONE WHO HAS 58 00:01:53,240 --> 00:01:54,400 PARTICIPATED YESTERDAY AND WHO 59 00:01:54,400 --> 00:01:56,040 IS PARTICIPATING TODAY IN THIS 60 00:01:56,040 --> 00:01:57,280 REALLY IMPORTANT WORKSHOP. 61 00:01:57,280 --> 00:01:59,680 WE KNOW THAT YOU'RE ALL VERY 62 00:01:59,680 --> 00:02:03,040 BUSY AND ESPECIALLY IN THE MIDST 63 00:02:03,040 --> 00:02:04,640 OF THE PANDEMIC, EVERYBODY'S GOT 64 00:02:04,640 --> 00:02:06,440 A LOT OF DEMANDS ON THEIR TIMES 65 00:02:06,440 --> 00:02:08,080 AND YOU CHOSE TO SPEND THIS TIME 66 00:02:08,080 --> 00:02:09,920 WITH US TO SHARE WITH US YOUR 67 00:02:09,920 --> 00:02:11,240 THOUGHTS ABOUT HOW WE CAN MOVE 68 00:02:11,240 --> 00:02:13,160 THIS FIELD FORWARD. 69 00:02:13,160 --> 00:02:17,040 AND WE GREATLY APPRECIATE THAT. 70 00:02:17,040 --> 00:02:18,680 THIS IS A REALLY IMPORTANT PART 71 00:02:18,680 --> 00:02:19,240 OF OUR MISSION. 72 00:02:19,240 --> 00:02:20,920 YOU HEARD ABOUT THAT YESTERDAY 73 00:02:20,920 --> 00:02:23,280 FROM DR. ZORINA GALIS, WHO 74 00:02:23,280 --> 00:02:24,480 SHARED WITH YOU THE EXTENT TO 75 00:02:24,480 --> 00:02:27,560 WHICH WE SUPPORT THIS IN THE 76 00:02:27,560 --> 00:02:29,200 MISSION OF THE DIVISION OF 77 00:02:29,200 --> 00:02:30,120 CARDIOVASCULAR SCIENCES AND THE 78 00:02:30,120 --> 00:02:32,160 NATIONAL HEART, LUNG AND BLOOD 79 00:02:32,160 --> 00:02:33,480 INSTITUTE, THE LYMPHATIC SYSTEM 80 00:02:33,480 --> 00:02:35,680 IS AN IMPORTANT PART OF THE 81 00:02:35,680 --> 00:02:36,640 VASCULAR SYSTEM SO IT'S REALLY 82 00:02:36,640 --> 00:02:38,280 AN IMPORTANT PART OF OUR MISSION 83 00:02:38,280 --> 00:02:39,720 IN THE DIVISION OF 84 00:02:39,720 --> 00:02:40,320 CARDIOVASCULAR SCIENCES. 85 00:02:40,320 --> 00:02:42,640 AS YOU SAW YESTERDAY IN 86 00:02:42,640 --> 00:02:45,800 DR. GALIS' PRESENTATION, THE 87 00:02:45,800 --> 00:02:46,960 COMMUNITY IS DOING REASONABLY 88 00:02:46,960 --> 00:02:51,280 WELL WITHIN THE PEER REVIEW 89 00:02:51,280 --> 00:02:53,600 PROCESS WITHIN NHLBI, WHERE THE 90 00:02:53,600 --> 00:02:55,480 SUCCESS RATE IS HIGHER THAN THE 91 00:02:55,480 --> 00:02:58,280 TYPICAL SUCCESS RATE FOR 92 00:02:58,280 --> 00:02:59,240 APPLICATIONS IN GENERAL. 93 00:02:59,240 --> 00:03:00,600 SO WE'RE VERY PLEASED TO SEE 94 00:03:00,600 --> 00:03:02,440 THAT, AND YET WE KNOW WE CAN DO 95 00:03:02,440 --> 00:03:04,880 MORE AND NEED TO DO MORE, AND, 96 00:03:04,880 --> 00:03:07,360 THEREFORE, HOSTING THIS WORKSHOP 97 00:03:07,360 --> 00:03:09,680 IN COLLABORATION WITH NIDDK, AND 98 00:03:09,680 --> 00:03:11,120 WE'RE LOOKING FORWARD TO YOUR 99 00:03:11,120 --> 00:03:12,400 INPUT. 100 00:03:12,400 --> 00:03:14,280 I WANTED TO SHARE WITH YOU MY 101 00:03:14,280 --> 00:03:15,760 EXCITEMENT ABOUT WHAT I SEE AS 102 00:03:15,760 --> 00:03:16,960 POTENTIAL OUTCOMES OF THIS 103 00:03:16,960 --> 00:03:18,400 WORKSHOP. 104 00:03:18,400 --> 00:03:19,520 FIRST WE'LL BE LOOKING FORWARD 105 00:03:19,520 --> 00:03:21,840 TO A REPORT THAT WE CAN POST ON 106 00:03:21,840 --> 00:03:23,880 THE NIH WEBSITE HOPEFULLY WITHIN 107 00:03:23,880 --> 00:03:25,720 THE NEXT, YOU KNOW, FOUR TO SIX 108 00:03:25,720 --> 00:03:27,160 WEEKS SO WE CAN GET IT OUT IN A 109 00:03:27,160 --> 00:03:28,480 TIMELY MANNER TO SHARE YOUR 110 00:03:28,480 --> 00:03:30,080 THOUGHTS AND YOUR INPUT WITH THE 111 00:03:30,080 --> 00:03:33,040 REST OF OF THE BIOMEDICAL RESH 112 00:03:33,040 --> 00:03:34,600 COMMUNITY AT LEAST AT A SUMMARY 113 00:03:34,600 --> 00:03:35,600 LEVEL, AND THEN WE ANTICIPATE 114 00:03:35,600 --> 00:03:38,680 YOU MAY WANT TO WRITE A PAPER 115 00:03:38,680 --> 00:03:40,160 FOR PUBLICATION IN PEER REVIEW 116 00:03:40,160 --> 00:03:41,880 JOURNAL AND IF YOU DECIDE TO DO 117 00:03:41,880 --> 00:03:42,880 THAT, WE'LL CERTAINLY SUPPORT 118 00:03:42,880 --> 00:03:44,680 YOU IN THAT EFFORT, AND WE WOULD 119 00:03:44,680 --> 00:03:46,120 AGAIN HOPE THAT WOULD GET 120 00:03:46,120 --> 00:03:47,320 SUBMITTED WITHIN THE NEXT SIX 121 00:03:47,320 --> 00:03:49,560 MONTHS OR SO AT THE OUTSIDE, SO 122 00:03:49,560 --> 00:03:51,000 THAT, AGAIN, IT'S TIMELY 123 00:03:51,000 --> 00:03:52,360 INFORMATION TO GET OUT TO THE 124 00:03:52,360 --> 00:03:52,960 PEER REVIEW COMMUNITY. 125 00:03:52,960 --> 00:03:55,520 WE KNOW YOU'RE VERY BUSY, SO 126 00:03:55,520 --> 00:03:57,360 THAT'S A TIGHT TIMELINE, BUT IF 127 00:03:57,360 --> 00:03:58,560 WE'RE GOING TO GET A REPORT OUT 128 00:03:58,560 --> 00:03:59,880 FROM THIS WORKSHOP, WE'D LIKE TO 129 00:03:59,880 --> 00:04:02,600 GET IT OUT IN A TIMELY MANNER, 130 00:04:02,600 --> 00:04:03,800 BEFORE THE INPUT AND 131 00:04:03,800 --> 00:04:05,120 PRESENTATIONS GET A LITTLE BIT 132 00:04:05,120 --> 00:04:05,440 DATED. 133 00:04:05,440 --> 00:04:06,640 SO WE'LL LOOK FORWARD TO 134 00:04:06,640 --> 00:04:07,840 SUPPORTING YOU ON THAT IF THAT'S 135 00:04:07,840 --> 00:04:11,480 SOMETHING YOU'D LIKE TO DO. 136 00:04:11,480 --> 00:04:12,760 WE ALSO HOPE THAT WHEN YOU GO 137 00:04:12,760 --> 00:04:15,960 HOME, YOU'LL BE ENERGIZED BY THE 138 00:04:15,960 --> 00:04:16,680 INTERACTIONS. 139 00:04:16,680 --> 00:04:19,560 I GUESS WE'RE HOME, BUT WHEN YOU 140 00:04:19,560 --> 00:04:21,080 GO BACK TO YOUR DAY TO DAY WORK, 141 00:04:21,080 --> 00:04:22,920 YOU'LL BE ENERGIZED BY THE 142 00:04:22,920 --> 00:04:24,040 INTERACTIONS OVER THE PAST DAY 143 00:04:24,040 --> 00:04:26,360 AND TODAY AND THAT YOU'LL SUBMIT 144 00:04:26,360 --> 00:04:28,200 ADDITIONAL GREAT APPLICATIONS. 145 00:04:28,200 --> 00:04:31,000 I TELL PEOPLE IT'S SIMPLE TO GET 146 00:04:31,000 --> 00:04:31,920 MONEY FROM NHLBI. 147 00:04:31,920 --> 00:04:33,440 WRITE A GREAT APPLICATION, GET A 148 00:04:33,440 --> 00:04:35,520 GREAT SCORE, ALMOST ALL THE 149 00:04:35,520 --> 00:04:37,320 MONEY WE GIVE OUT EVERY YEAR 150 00:04:37,320 --> 00:04:39,360 GOES IN PEER REVIEWED 151 00:04:39,360 --> 00:04:40,200 INVESTIGATOR-INITIATED RESEARCH. 152 00:04:40,200 --> 00:04:41,000 I DID SAY SIMPLE. 153 00:04:41,000 --> 00:04:45,360 I DIDN'T SAY EASY. 154 00:04:45,360 --> 00:04:47,320 YOU KNOW, SOMETIMES WE USE THE 155 00:04:47,320 --> 00:04:48,440 INPUT FROM THESE KINDS OF 156 00:04:48,440 --> 00:04:50,600 WORKSHOPS TO PUT OUT SPECIFIC 157 00:04:50,600 --> 00:04:51,240 FUNDING OPPORTUNITIES. 158 00:04:51,240 --> 00:04:53,120 I WILL SAY WE DO MORE WORKSHOPS 159 00:04:53,120 --> 00:04:56,520 THAN WE CAN POSSIBLY PUT OUT 160 00:04:56,520 --> 00:04:57,760 FUNDING OPPORTUNITIES, SO WE 161 00:04:57,760 --> 00:04:59,800 DON'T ALWAYS DO THAT, THOUGH. 162 00:04:59,800 --> 00:05:01,360 WE SOMETIMES DO, SO BASED ON 163 00:05:01,360 --> 00:05:03,480 YOUR INPUT, WE MAY PUT OUT A 164 00:05:03,480 --> 00:05:05,920 FUNDING OPPORTUNITY 165 00:05:05,920 --> 00:05:06,360 ANNOUNCEMENT. 166 00:05:06,360 --> 00:05:07,560 REGARDLESS OF THAT, WE'LL USE 167 00:05:07,560 --> 00:05:09,200 YOUR INPUT TO GUIDE WHAT WE CALL 168 00:05:09,200 --> 00:05:11,080 OUR SELECT PAY PROCESS, IN WHICH 169 00:05:11,080 --> 00:05:13,440 WE PUT A LITTLE BIT OF MONEY 170 00:05:13,440 --> 00:05:16,640 ASIDE TO PICK UP HIGH PRIORITY 171 00:05:16,640 --> 00:05:18,080 APPLICATIONS THAT ARE JUST ON 172 00:05:18,080 --> 00:05:20,280 THE WRONG SIDE OF THE PAYLINE, 173 00:05:20,280 --> 00:05:22,560 BUT ARE HIGHLY STRATEGIC, HIGHLY 174 00:05:22,560 --> 00:05:23,320 ALIGNED WITH OUR MISSION. 175 00:05:23,320 --> 00:05:25,160 SO WE WILL USE YOUR INPUT TO 176 00:05:25,160 --> 00:05:27,280 HELP GUIDE THAT PROCESS AS WELL. 177 00:05:27,280 --> 00:05:29,320 SO I WANT TO END WHERE I 178 00:05:29,320 --> 00:05:30,320 STARTED, WITH THANKING YOU AND 179 00:05:30,320 --> 00:05:32,520 THE ORGANIZERS OF THE WORKSHOP 180 00:05:32,520 --> 00:05:34,080 FOR COMING TOGETHER TO HELP US 181 00:05:34,080 --> 00:05:35,840 ADDRESS THIS REALLY IMPORTANT 182 00:05:35,840 --> 00:05:36,200 PROBLEM. 183 00:05:36,200 --> 00:05:37,440 WE'RE LOOKING FORWARD TO YOUR 184 00:05:37,440 --> 00:05:40,480 INPUT AND TO LEVERAGING TO MOVE 185 00:05:40,480 --> 00:05:41,600 THIS FIELD FORWARD. 186 00:05:41,600 --> 00:05:43,360 AND WITH THAT, I'LL PASS THE 187 00:05:43,360 --> 00:05:45,440 BATON BACK TO THE CHAIRS TO GET 188 00:05:45,440 --> 00:05:47,160 US KICKED OFF TODAY. 189 00:05:47,160 --> 00:05:51,760 THANKS SO MUCH. 190 00:05:51,760 --> 00:05:53,080 >> THANK YOU SO MUCH, DR. GOFF. 191 00:05:53,080 --> 00:05:55,040 THAT WAS A VERY INSPIRING TALK. 192 00:05:55,040 --> 00:05:57,240 IT'S MY PLEASURE THIS MORNING TO 193 00:05:57,240 --> 00:05:59,120 INTRODUCE DR. STANLEY ROCKSON AS 194 00:05:59,120 --> 00:06:01,520 OUR NEXT KEYNOTE SPEAKER. 195 00:06:01,520 --> 00:06:03,400 DR. ROCKSON DOESN'T NEED AN 196 00:06:03,400 --> 00:06:04,240 INTRODUCTION, ALL OF US KNOW 197 00:06:04,240 --> 00:06:07,720 HIM, BUT HE'S ALSO THE PROFESSOR 198 00:06:07,720 --> 00:06:09,560 OF LYMPHATIC RESEARCH AND THE 199 00:06:09,560 --> 00:06:11,800 CHIEF OF CONSULTIVE CARDIOLOGY 200 00:06:11,800 --> 00:06:13,840 DIVISION AT STANFORD. 201 00:06:13,840 --> 00:06:15,280 DR. ROCKSON IS A PIONEER IN 202 00:06:15,280 --> 00:06:16,000 LYMPHATIC RESEARCH. 203 00:06:16,000 --> 00:06:17,680 HE WAS KIND ENOUGH TO MENTOR ME 204 00:06:17,680 --> 00:06:19,320 WHEN I WAS FIRST GETTING STARTED 205 00:06:19,320 --> 00:06:20,080 IN THIS AREA. 206 00:06:20,080 --> 00:06:21,480 HIS IMPORTANT WORK IN THE ROLE 207 00:06:21,480 --> 00:06:23,680 OF INFLAMMATION AS REGULATOR OF 208 00:06:23,680 --> 00:06:24,800 LYMPHEDEMA DEVELOPMENT HAS LED 209 00:06:24,800 --> 00:06:27,200 TO NUMEROUS CLINICAL TRIALS AND 210 00:06:27,200 --> 00:06:29,160 HAS BEEN A CATALYST FOR MANY 211 00:06:29,160 --> 00:06:29,920 OTHER LABORATORIES INCLUDING 212 00:06:29,920 --> 00:06:30,520 MINE. 213 00:06:30,520 --> 00:06:32,120 PLEASE JOIN ME IN WELCOMING 214 00:06:32,120 --> 00:06:33,760 DR. ROCKSON. 215 00:06:33,760 --> 00:06:35,720 >> BABAK, THANK YOU SO MUCH. 216 00:06:35,720 --> 00:06:39,960 THANK YOU TO THE ORGANIZERS, 217 00:06:39,960 --> 00:06:42,160 INCLUDING YOURSELF, FOR THIS 218 00:06:42,160 --> 00:06:43,160 WONDERFUL INVITATION. 219 00:06:43,160 --> 00:06:45,240 I'M JUST TRYING TO SHARE MY 220 00:06:45,240 --> 00:06:55,280 SCREEN HERE. 221 00:06:55,280 --> 00:06:56,200 THIS IS NOT WORKING. 222 00:06:56,200 --> 00:07:03,680 IT WORKED A MOMENT AGO. 223 00:07:03,680 --> 00:07:04,920 I'M SO SORRY, I DON'T KNOW 224 00:07:04,920 --> 00:07:06,240 WHAT'S HAPPENING. 225 00:07:06,240 --> 00:07:08,000 WE JUST TESTED THIS AND NOW IT 226 00:07:08,000 --> 00:07:10,680 WON'T GO TO "SHARE SCREEN." 227 00:07:10,680 --> 00:07:13,280 >> I THINK ZOOM IS SOMETIMES 228 00:07:13,280 --> 00:07:14,760 LIKE THE LAB, SOMETHING THAT 229 00:07:14,760 --> 00:07:16,960 WORKED EVERY TIME THE LAST 10 230 00:07:16,960 --> 00:07:19,680 TIMES YOU DO IT, AND IT DOESN'T 231 00:07:19,680 --> 00:07:20,520 WORK INEXPLICABLY. 232 00:07:20,520 --> 00:07:20,920 >> RIGHT. 233 00:07:20,920 --> 00:07:22,160 LET ME START ONE MORE TIME, SEE 234 00:07:22,160 --> 00:07:29,760 WHAT HAPPENS. 235 00:07:29,760 --> 00:07:31,080 I'M SORRY, I DON'T KNOW WHAT THE 236 00:07:31,080 --> 00:07:32,280 PROBLEM IS. 237 00:07:32,280 --> 00:07:34,000 IT WON'T ALLOW ME TO -- 238 00:07:34,000 --> 00:07:35,360 >> ARE YOU CLICKING ON THE SHARE 239 00:07:35,360 --> 00:07:39,320 SCREEN BUTTON AT THE BO M BOF 240 00:07:39,320 --> 00:07:39,720 YOUR SCREEN? 241 00:07:39,720 --> 00:07:41,480 >> YES, I'M SELECTING POWERPOINT 242 00:07:41,480 --> 00:07:43,320 AND IT JUST SHIFTS BACK TO THE 243 00:07:43,320 --> 00:07:43,560 DESKTOP. 244 00:07:43,560 --> 00:07:45,280 >> DO YOU HAVE YOUR POWERPOINTS 245 00:07:45,280 --> 00:07:45,880 OPEN ALREADY? 246 00:07:45,880 --> 00:07:46,720 >> YES. 247 00:07:46,720 --> 00:07:47,360 YES. 248 00:07:47,360 --> 00:07:49,880 WE JUST TESTED IT A MOMENT AGO. 249 00:07:49,880 --> 00:07:51,520 IS THAT SHARING NOW? 250 00:07:51,520 --> 00:07:52,400 >> NO. 251 00:07:52,400 --> 00:07:53,320 IT'S NOT. 252 00:07:53,320 --> 00:07:54,600 >> OKAY. 253 00:07:54,600 --> 00:07:57,840 LET ME TRY ONE MORE TIME. 254 00:07:57,840 --> 00:07:59,400 MY MACHINE MAKES IT LOOK AS IF 255 00:07:59,400 --> 00:08:09,880 IT IS SHARING, BUT -- THIS IS 256 00:08:11,600 --> 00:08:11,960 TERRIBLE. 257 00:08:11,960 --> 00:08:16,760 LET'S TRY ONE MORE TIME. 258 00:08:16,760 --> 00:08:18,000 I'M SO SOOR EE. 259 00:08:18,000 --> 00:08:20,000 I CAN'T MAKE THIS SHARE. 260 00:08:20,000 --> 00:08:23,720 I DON'T KNOW WHAT'S HAPPENED. 261 00:08:23,720 --> 00:08:26,320 >> STAN, DO YOU WANT TO LOG OFF 262 00:08:26,320 --> 00:08:29,200 AND JOIN BACK ON? 263 00:08:29,200 --> 00:08:30,920 WE CAN MAYBE SHOW THEM FROM 264 00:08:30,920 --> 00:08:31,120 HERE? 265 00:08:31,120 --> 00:08:32,240 >> WOULD YOU LIKE ME TO SHARE 266 00:08:32,240 --> 00:08:34,600 THEM FOR YOU? 267 00:08:34,600 --> 00:08:37,240 >> PERHAPS -- WELL, WHY DON'T I 268 00:08:37,240 --> 00:08:38,480 QUICKLY LOG OFF AND SEE IF I CAN 269 00:08:38,480 --> 00:08:39,880 MAKE THAT WORK. 270 00:08:39,880 --> 00:08:40,720 >> OKAY. 271 00:08:40,720 --> 00:08:42,360 WE CAN GO ON TO THE NEXT 272 00:08:42,360 --> 00:08:42,600 SPEAKER. 273 00:08:42,600 --> 00:08:43,360 >> YEAH. 274 00:08:43,360 --> 00:08:50,560 WHY DON'T WE DO THAT. 275 00:08:50,560 --> 00:08:55,400 >> OKAY, SARAH, ARE YOU READY? 276 00:08:55,400 --> 00:08:58,800 IS SARAH TEICHMANN HERE? 277 00:08:58,800 --> 00:09:00,880 >> WE MIGHT HAVE TO WAIT JUST 278 00:09:00,880 --> 00:09:03,280 ONE SECOND FOR DR. ROCKSON 279 00:09:03,280 --> 00:09:13,760 BECAUSE SARAH IS JOINING US. 280 00:09:14,560 --> 00:09:16,720 >> JOHN, I DON'T KNOW IF WE CAN 281 00:09:16,720 --> 00:09:18,600 SHARE DR. ROCKSON'S SLIDES, 282 00:09:18,600 --> 00:09:20,760 BUT -- OR IF IT WOULD GET IN HIS 283 00:09:20,760 --> 00:09:28,240 WAY WHEN HE'S TRYING AGAIN? 284 00:09:28,240 --> 00:09:30,280 >> I OFFERED. 285 00:09:30,280 --> 00:09:31,120 HE DECLINED. 286 00:09:31,120 --> 00:09:32,480 >> SORRY, EVERYONE. 287 00:09:32,480 --> 00:09:33,240 JUST ONE MORE MINUTE. 288 00:09:33,240 --> 00:09:34,480 I'M SURE IT WILL BE WORTHWHILE 289 00:09:34,480 --> 00:09:42,000 TO WAIT. 290 00:09:42,000 --> 00:09:44,400 >> SELEN, IT'S DHRUV. 291 00:09:44,400 --> 00:09:46,480 I THINK I'M THE NEXT SPEAKER 292 00:09:46,480 --> 00:09:47,280 AFTER SARAH. 293 00:09:47,280 --> 00:09:48,880 I'M READY, JUST SO YOU KNOW, IN 294 00:09:48,880 --> 00:09:50,320 CASE THERE'S A DELAY. 295 00:09:50,320 --> 00:09:55,480 >> THANKS, DHRUV. 296 00:09:55,480 --> 00:09:57,920 >> LOOK AT DHRUV, STEPPING UP! 297 00:09:57,920 --> 00:09:59,080 >> I KNOW, RIGHT? 298 00:09:59,080 --> 00:10:02,760 >> HE'S STILL COMING TO THE 299 00:10:02,760 --> 00:10:03,000 RESCUE. 300 00:10:03,000 --> 00:10:04,600 >> TAKING A CONSULT. 301 00:10:04,600 --> 00:10:06,200 >> RIGHT? 302 00:10:06,200 --> 00:10:12,640 >> OKAY. 303 00:10:12,640 --> 00:10:13,760 STAN, WE ARE WAITING FOR YOU. 304 00:10:13,760 --> 00:10:15,440 IF YOU ARE READY TO TRY, LET'S 305 00:10:15,440 --> 00:10:16,160 DO IT AGAIN. 306 00:10:16,160 --> 00:10:18,440 >> I'LL KEEP MY FINGERS CROSSED 307 00:10:18,440 --> 00:10:18,640 HERE. 308 00:10:18,640 --> 00:10:20,080 >> HERE YOU GO. 309 00:10:20,080 --> 00:10:20,280 AWESOME! 310 00:10:20,280 --> 00:10:21,040 >> THANK YOU. 311 00:10:21,040 --> 00:10:24,120 I'M SO SOOR EE. 312 00:10:24,120 --> 00:10:25,720 SORRY. 313 00:10:25,720 --> 00:10:27,160 LET ME TRY AGAIN. 314 00:10:27,160 --> 00:10:29,040 THANKS AGAIN TO THE ORGANIZERS 315 00:10:29,040 --> 00:10:30,240 NOW, ALSO THANK YOU FOR BEING 316 00:10:30,240 --> 00:10:32,760 PATIENT AND WAITING FOR ME. 317 00:10:32,760 --> 00:10:34,160 THIS IS REALLY A PRIVILEGE TO BE 318 00:10:34,160 --> 00:10:36,160 ABLE TO BE A PART OF THIS VERY 319 00:10:36,160 --> 00:10:38,000 GROUND BREAKING CONFERENCE. 320 00:10:38,000 --> 00:10:40,520 SO I'M GOING TO TALK ABOUT A 321 00:10:40,520 --> 00:10:41,800 TRIP THAT'S ALREADY BEEN, I 322 00:10:41,800 --> 00:10:44,040 THINK, OVER 20 YEARS IN 323 00:10:44,040 --> 00:10:45,640 DURATION, AND I ONLY HAVE 20 324 00:10:45,640 --> 00:10:47,200 MINUTES SO I'LL TRY TO BREEZE 325 00:10:47,200 --> 00:10:48,840 THROUGH IT BUT GIVE YOU THE 326 00:10:48,840 --> 00:10:50,680 HIGHLIGHTS OF WHERE WE'VE BEEN. 327 00:10:50,680 --> 00:10:53,200 AND OF COURSE THE ISSUE IS, HOW 328 00:10:53,200 --> 00:10:54,840 DO WE TREAT AND POTENTIALLY 329 00:10:54,840 --> 00:10:57,360 REVERSE OR EVEN POTENTIALLY 330 00:10:57,360 --> 00:10:58,760 PREVENT THIS PROBLEM, WHICH IS 331 00:10:58,760 --> 00:11:02,600 SOME RELATIVELY ADVANCED 332 00:11:02,600 --> 00:11:05,360 MANIFESTATIONS OF LYMPHEDEMA. 333 00:11:05,360 --> 00:11:07,080 SO WHAT YOU SAW IN THE PRECEDING 334 00:11:07,080 --> 00:11:10,040 SLIDE IS ACTUALLY STAGE THREE 335 00:11:10,040 --> 00:11:11,680 LYMPHEDEMA BY ISL CRITERIA. 336 00:11:11,680 --> 00:11:12,880 AND AS YOU GO THROUGH THIS 337 00:11:12,880 --> 00:11:14,280 SEQUENCE FROM SUBCLINICAL 338 00:11:14,280 --> 00:11:16,720 DISEASE TO FULLY EXPRESSED 339 00:11:16,720 --> 00:11:18,160 DISEASE, YOU SEE THAT WHAT WE 340 00:11:18,160 --> 00:11:21,640 ARE FEATURING IS THE INCREASING 341 00:11:21,640 --> 00:11:23,400 PRESENCE OF TISSUE DISTORTION 342 00:11:23,400 --> 00:11:25,680 AND PATHOLOGY AS A CONSEQUENCE 343 00:11:25,680 --> 00:11:27,520 OF THE CHRONIC EDEMA. 344 00:11:27,520 --> 00:11:30,520 AND WHILE WE HAVE REASONABLE 345 00:11:30,520 --> 00:11:32,800 APPROACHES TO CONTROL EDEMA AND 346 00:11:32,800 --> 00:11:35,720 INTERSTITIAL FLUID ACCUMULATION, 347 00:11:35,720 --> 00:11:37,800 BOTH DIURETICS AS WELL AS 348 00:11:37,800 --> 00:11:39,840 MECHANICAL INTERVENTIONS, WE 349 00:11:39,840 --> 00:11:41,880 HAVE HAD HISTORICALLY LITTLE OR 350 00:11:41,880 --> 00:11:42,640 NOTHING TO DO OTHER THAN 351 00:11:42,640 --> 00:11:45,480 SURGICAL REMOVAL FOR THE TISSUE 352 00:11:45,480 --> 00:11:47,200 DISTORTION THAT OCCURS WITH 353 00:11:47,200 --> 00:11:47,600 CHRONIC EDEMA. 354 00:11:47,600 --> 00:11:50,600 SO WE GO FROM THIS STATE, CLEAR 355 00:11:50,600 --> 00:11:54,280 PITTING EDEMA, HERE I'VE LEFT MY 356 00:11:54,280 --> 00:11:56,160 EXAMINER FINGER IMPRESSION ON 357 00:11:56,160 --> 00:11:59,920 THE SURFACE OF THE LIMB, TO AN 358 00:11:59,920 --> 00:12:01,480 IDENTICAL INCREASE IN LIMB 359 00:12:01,480 --> 00:12:03,520 VOLUME BUT WITHOUT ANY ABILITY 360 00:12:03,520 --> 00:12:05,840 TO DISTORT THE FLUID CONTENT 361 00:12:05,840 --> 00:12:09,120 BECAUSE NOW THIS HAS BECOME 362 00:12:09,120 --> 00:12:11,600 PREDOMINANTLY TISSUE OVERGROWTH. 363 00:12:11,600 --> 00:12:13,360 SO THE QUESTION IS, HOW DO WE 364 00:12:13,360 --> 00:12:15,360 DEVELOP A DRUG TO REVERSE AND 365 00:12:15,360 --> 00:12:15,880 PREVENT LYMPHEDEMA? 366 00:12:15,880 --> 00:12:18,680 SO WE STARTED, OF COURSE, IN THE 367 00:12:18,680 --> 00:12:20,240 ANIMAL AND AS IS OFTEN THE CASE, 368 00:12:20,240 --> 00:12:23,000 WE RESORT TO OUR FRIENDS THE 369 00:12:23,000 --> 00:12:24,760 MICE, BECAUSE THEY REPRESENT 370 00:12:24,760 --> 00:12:28,360 THIS BEAUTIFUL THROUGHPUT 371 00:12:28,360 --> 00:12:29,240 OPPORTUNITY TO EXPLORE THESE 372 00:12:29,240 --> 00:12:30,440 DISEASE PROCESSES. 373 00:12:30,440 --> 00:12:33,840 SO WE DEVELOPED AND MODIFIED A 374 00:12:33,840 --> 00:12:36,360 MODEL OF HUMAN LYMPHEDEMA IN THE 375 00:12:36,360 --> 00:12:37,760 MURINE TAIL, IN WHICH WE ALLOW 376 00:12:37,760 --> 00:12:43,520 THE TAIL TO BE THE SIMULACRUM OF 377 00:12:43,520 --> 00:12:44,720 THE EDEMATOUS LIMB, WE DEVELOPED 378 00:12:44,720 --> 00:12:46,320 A PHOTO TECHNIQUE TO BE ABLE TO 379 00:12:46,320 --> 00:12:48,280 VERY ACCURATELY MEASURE CHANGES 380 00:12:48,280 --> 00:12:50,320 IN TAIL VOLUME AS WE INTERVENED 381 00:12:50,320 --> 00:12:52,520 IN THIS MODEL, AND WHAT WE WERE 382 00:12:52,520 --> 00:12:56,160 ABLE TO IDENTIFY AND SUPPORT IS 383 00:12:56,160 --> 00:12:59,760 THE NOTION THAT MURINE 384 00:12:59,760 --> 00:13:02,160 LYMPHEDEMA LOOKS VERY MUCH LIKE 385 00:13:02,160 --> 00:13:04,560 ANIMAL -- LIKE HUMAN LYMPHEDEMA 386 00:13:04,560 --> 00:13:06,640 UNDER THE MICROSCOPE WITH THIS 387 00:13:06,640 --> 00:13:07,240 TREMENDOUS EXPANSION OF THE 388 00:13:07,240 --> 00:13:10,240 DERMIS AND THE SUBDERMIS, WITH 389 00:13:10,240 --> 00:13:11,920 INFLAMMATORY CELL COMPONENTS, 390 00:13:11,920 --> 00:13:14,320 DILATION OF THE MICRO 391 00:13:14,320 --> 00:13:15,520 LYMPHATICS, AND GENERAL 392 00:13:15,520 --> 00:13:16,840 DISTORTION OF THE ANATOMY THAT 393 00:13:16,840 --> 00:13:20,560 WE ALSO SEE IN THE HUMAN 394 00:13:20,560 --> 00:13:23,800 SETTING. 395 00:13:23,800 --> 00:13:25,200 WHAT WE'RE ABLE TO SEE IS THAT 396 00:13:25,200 --> 00:13:27,000 IN THE UNTREATED STATE, WE SEE 397 00:13:27,000 --> 00:13:31,360 THESE TREMENDOUS LAKES OF 398 00:13:31,360 --> 00:13:32,320 MICROLYMPHATIC EXPANSION, AND 399 00:13:32,320 --> 00:13:34,160 WHAT WE'VE BEEN ABLE TO SEE IN 400 00:13:34,160 --> 00:13:36,400 THE TREATMENT SETTING IS THAT AS 401 00:13:36,400 --> 00:13:39,240 WE REVERSE THE LYMPHEDEMA AT THE 402 00:13:39,240 --> 00:13:40,520 TISSUE LEVEL, WE ACTUALLY CAN 403 00:13:40,520 --> 00:13:43,760 SEE THAT THESE MICROLYMPHATICS 404 00:13:43,760 --> 00:13:46,480 RETURN TO THEIR NORMAL 405 00:13:46,480 --> 00:13:48,120 NON-DILATED STATE WITH 406 00:13:48,120 --> 00:13:51,800 PHARMACOLOGIC INTERVENTION. 407 00:13:51,800 --> 00:13:53,160 BUT TO GO BACK TO THE BEGINNING 408 00:13:53,160 --> 00:13:54,760 OF THE STORY, WE TOOK THE MODEL 409 00:13:54,760 --> 00:13:57,280 AND DECIDED TO COMPARE SURGICAL 410 00:13:57,280 --> 00:13:58,920 SHAM MODELS WITH THOSE THAT 411 00:13:58,920 --> 00:14:00,680 DEVELOPED THE DISEASE WITHOUT 412 00:14:00,680 --> 00:14:02,160 TREATMENT, AND WE USED WHAT AT 413 00:14:02,160 --> 00:14:04,200 THE TIME WAS CUTTING EDGE 414 00:14:04,200 --> 00:14:06,800 TECHNOLOGY, NOW NOT SO MUCH, OF 415 00:14:06,800 --> 00:14:08,240 WHOLE GENOME TRANSCRIPTIONAL 416 00:14:08,240 --> 00:14:09,520 PROFILING THROUGH MICRO ARRAY, 417 00:14:09,520 --> 00:14:11,640 AND WHAT WE WERE VERY SURPRISED 418 00:14:11,640 --> 00:14:14,560 TO FIND AT THAT EARLY STAGE OF 419 00:14:14,560 --> 00:14:17,480 THIS PROCESS IS THE TREMENDOUS 420 00:14:17,480 --> 00:14:19,520 PREDOMINENCE OF INFLAMMATORY AND 421 00:14:19,520 --> 00:14:22,000 IMMUNE MECHANISMS AS BEING A 422 00:14:22,000 --> 00:14:25,560 PART OF THE EXPRESSION OF THE 423 00:14:25,560 --> 00:14:26,600 DISEASE, WITH VERY LITTLE 424 00:14:26,600 --> 00:14:28,680 ACTUALLY RELATED TO THE VASCULAR 425 00:14:28,680 --> 00:14:30,200 PROCESSES THEMSELVES. 426 00:14:30,200 --> 00:14:33,480 AND THIS, OF COURSE, HELPED US 427 00:14:33,480 --> 00:14:35,200 TO IDENTIFY AND SUPPORT THE 428 00:14:35,200 --> 00:14:38,080 NOTION THAT THE LYMPHATICS ARE 429 00:14:38,080 --> 00:14:40,040 NOT ONLY A COMPONENT OF THE 430 00:14:40,040 --> 00:14:40,920 CIRCULATION, AND OF COURSE 431 00:14:40,920 --> 00:14:42,560 THEY'RE VITAL HERE, BUT THEY ARE 432 00:14:42,560 --> 00:14:46,160 ALSO PART OF THE IMMUNE SYSTEM 433 00:14:46,160 --> 00:14:49,880 AND THIS IS REALLY AN 434 00:14:49,880 --> 00:14:52,040 IMMUNOCIRCULATORY SYSTEM, AND IT 435 00:14:52,040 --> 00:14:53,800 IS VERY LIKELY THAT THE 436 00:14:53,800 --> 00:14:54,600 INFLAMMATORY AND IMMUNE 437 00:14:54,600 --> 00:14:58,080 COMPONENTS RELATE TO THIS ASPECT 438 00:14:58,080 --> 00:14:59,840 OF LYMPHATIC FUNCTION, LEADING 439 00:14:59,840 --> 00:15:01,680 US TO BELIEVE THAT CHRONIC 440 00:15:01,680 --> 00:15:02,880 INFLAMMATION HAS A GREAT ROLE TO 441 00:15:02,880 --> 00:15:06,000 PLAY IN THE PATHOGEN PATHOE 442 00:15:06,000 --> 00:15:07,280 FULLY EXPRESSED DISEASE AND THAT 443 00:15:07,280 --> 00:15:08,600 THIS MIGHT BE A REASONABLE 444 00:15:08,600 --> 00:15:09,400 TARGET FOR INTERVENTION. 445 00:15:09,400 --> 00:15:12,680 AS WE LOOKED COMPARE CAREFUR 446 00:15:12,680 --> 00:15:14,640 MICRO ARRAY OUTPUT, WE WERE VERY 447 00:15:14,640 --> 00:15:18,000 STRUCK BY THE FACT THAT 5LO 448 00:15:18,000 --> 00:15:20,800 APPEARED AS A VERY PROMINENT AND 449 00:15:20,800 --> 00:15:23,800 UNEXPECTED FEATURE OF THE 450 00:15:23,800 --> 00:15:24,920 INFLAMMATORY RESPONSE, AND THIS 451 00:15:24,920 --> 00:15:26,640 HAD NOT RECEIVED MUCH ATTENTION 452 00:15:26,640 --> 00:15:28,600 UP UNTIL THAT POINT, AND WE 453 00:15:28,600 --> 00:15:30,480 DECIDED TO USE IT AS ONE OF THE 454 00:15:30,480 --> 00:15:34,080 TARGETS FOR OUR EMPIRICALLY 455 00:15:34,080 --> 00:15:36,000 DRIVEN INTERVENTION, SO WE CHOSE 456 00:15:36,000 --> 00:15:40,080 A NONSTEROIDAL ANTI-INFLAMMATORY 457 00:15:40,080 --> 00:15:42,200 DRUG THAT HAS THE ABILITY TO 458 00:15:42,200 --> 00:15:43,160 SIMULTANEOUSLY BLOCK THE 459 00:15:43,160 --> 00:15:45,800 ACTIVATION OF BOTH 5LO AND SIGH 460 00:15:45,800 --> 00:15:47,520 CROW OXYGENASE AS DO ALL THE 461 00:15:47,520 --> 00:15:48,880 OTHER NSAIDs, AND WHAT WE 462 00:15:48,880 --> 00:15:51,040 FOUND USING THIS AGENT IS THAT 463 00:15:51,040 --> 00:15:53,800 IT HAD A FUNDAMENTALLY NO EFFECT 464 00:15:53,800 --> 00:15:57,400 IN THE NORMAL SETTING BUT WHEN 465 00:15:57,400 --> 00:15:59,040 WE LOOKED AT ITS APPLICATION 466 00:15:59,040 --> 00:16:00,480 WHEN GIVEN SYSTEMICALLY TO THE 467 00:16:00,480 --> 00:16:02,000 DISEASED ANIMALS, PLACEBO, OF 468 00:16:02,000 --> 00:16:04,600 COURSE, HAD NO EFFECT, BUT THE 469 00:16:04,600 --> 00:16:06,200 DRUG IN A VERY SHORT PERIOD OF 470 00:16:06,200 --> 00:16:09,640 TIME NOT ONLY REVERSED THE 471 00:16:09,640 --> 00:16:10,560 EDEMATOUS PRESENTATION AS WE 472 00:16:10,560 --> 00:16:13,400 MEASURED IT BUT ALSO REVERTED 473 00:16:13,400 --> 00:16:17,520 THE SKIN ANATOMY TO 474 00:16:17,520 --> 00:16:19,080 FUNDAMENTALLY A NEAR NORMAL 475 00:16:19,080 --> 00:16:20,080 APPEARANCE IN A VERY SHORT 476 00:16:20,080 --> 00:16:20,600 PERIOD OF TIME. 477 00:16:20,600 --> 00:16:22,040 THIS WAS EXTRAORDINARILY 478 00:16:22,040 --> 00:16:23,440 ENCOURAGING TO US BECAUSE UP 479 00:16:23,440 --> 00:16:29,880 UNTIL THAT POINT IT WAS BELIEVED 480 00:16:29,880 --> 00:16:30,840 PATHOLOGICAL STRUCTURES OF 481 00:16:30,840 --> 00:16:32,360 LYMPHEDEMA WERE THE SO-CALLED 482 00:16:32,360 --> 00:16:33,280 IRREVERSIBLE FACTORS IN THE 483 00:16:33,280 --> 00:16:34,600 DISEASE, AND YET HERE WE HAD 484 00:16:34,600 --> 00:16:36,520 EVIDENCE THAT THERE WAS 485 00:16:36,520 --> 00:16:37,320 REVERSIBILITY EVEN INCLUDING 486 00:16:37,320 --> 00:16:39,800 SOME REVERSIBILITY OF THE 487 00:16:39,800 --> 00:16:40,800 FIBROSIS COMPONENT RELATED TO 488 00:16:40,800 --> 00:16:41,920 LYMPHEDEMA. 489 00:16:41,920 --> 00:16:45,280 THIS ALLOWED US TO RELATIVELY 490 00:16:45,280 --> 00:16:48,440 EARLY ON MOVE AHEAD TO LOOKING 491 00:16:48,440 --> 00:16:52,400 AT THE APPLICATION OF THIS -- OF 492 00:16:52,400 --> 00:16:53,920 THIS COMMERCIALLY AVAILABLE DRUG 493 00:16:53,920 --> 00:16:58,080 IN HUMAN LYMPHEDEMA AND WE 494 00:16:58,080 --> 00:17:00,280 DECIDED TO LOOK AT SKIN 495 00:17:00,280 --> 00:17:02,680 THICKNESS BY CALIPER MEASUREMENT 496 00:17:02,680 --> 00:17:04,680 AS A WAY TO TRACK SOME OF THE 497 00:17:04,680 --> 00:17:06,560 CHANGES THAT WE SAW UNDER THE 498 00:17:06,560 --> 00:17:07,720 MICROSCOPE IN THE MOUSE MODEL, 499 00:17:07,720 --> 00:17:10,320 SO HERE YOU SEE A REPRESENTATIVE 500 00:17:10,320 --> 00:17:12,520 SUBJECT IN ONE OF THESE TRIALS 501 00:17:12,520 --> 00:17:15,480 STARTING WITH A DISTENDABLE SKIN 502 00:17:15,480 --> 00:17:17,360 THICKNESS OF 35 MILLIMETERS, 503 00:17:17,360 --> 00:17:19,520 WHICH WENT DOWN AFTER IN THIS 504 00:17:19,520 --> 00:17:21,800 CASE A FOUR-MONTH EXPOSURE TO 505 00:17:21,800 --> 00:17:24,200 THE DRUG DOWN TO ABOUT 3 OR 506 00:17:24,200 --> 00:17:24,960 4 MILLIMETERS. 507 00:17:24,960 --> 00:17:27,920 VERY CLOSE TO WHAT ONE WOULD 508 00:17:27,920 --> 00:17:28,400 CONSIDER NORMAL. 509 00:17:28,400 --> 00:17:29,600 SO THIS WAS QUITE ENCOURAGING, 510 00:17:29,600 --> 00:17:32,160 AND WE SAW THIS AS A GENERAL 511 00:17:32,160 --> 00:17:35,080 TREND IN THE TRIAL SO THAT THE 512 00:17:35,080 --> 00:17:37,120 PRIMARY END POINT OF CALIPER 513 00:17:37,120 --> 00:17:39,440 THICKNESS WAS MET BY THE TRIAL. 514 00:17:39,440 --> 00:17:41,400 WE ALSO EE WILL BE RATED AN 515 00:17:41,400 --> 00:17:42,560 EMPIRIC HISTOLOGIC SCORE TO LOOK 516 00:17:42,560 --> 00:17:45,000 AT SOME OF THE ATTRIBUTES UNDER 517 00:17:45,000 --> 00:17:46,520 THE MICROSCOPE AND WE FOUND THAT 518 00:17:46,520 --> 00:17:48,720 THE PATIENTS ENROLLED IN THE 519 00:17:48,720 --> 00:17:51,040 TRIAL ACTUALLY EXPERIENCED A 520 00:17:51,040 --> 00:17:53,760 VERY SUBSTANTIAL IMPROVEMENT IN 521 00:17:53,760 --> 00:17:56,600 HISTOPATHOLOGY AS WELL. 522 00:17:56,600 --> 00:17:58,360 NOT SURPRISINGLY 523 00:17:58,360 --> 00:17:59,800 HISTOIMMUNOCHEMISTRY TO LOOK FOR 524 00:17:59,800 --> 00:18:03,040 EXPRESSION OF 5-LO AND ITS 525 00:18:03,040 --> 00:18:08,960 REDUCTION WITH KETOPROFEN WAS 526 00:18:08,960 --> 00:18:09,400 SUCCESSFUL. 527 00:18:09,400 --> 00:18:10,920 THIS LED US BACK TO THE ANIMAL 528 00:18:10,920 --> 00:18:13,440 MODEL BECAUSE NOW WE WERE VERY 529 00:18:13,440 --> 00:18:16,400 INTERESTED TO KNOW IS THIS 530 00:18:16,400 --> 00:18:18,160 CYCLOOXYGENASE CAUSING 531 00:18:18,160 --> 00:18:20,560 IMPROVEMENT, 5-LO INHIBITION OR 532 00:18:20,560 --> 00:18:21,840 SOME COMBINATION OF THE TWO? 533 00:18:21,840 --> 00:18:23,280 AT THIS POINT I HAD THE 534 00:18:23,280 --> 00:18:25,600 SERENDIPITY TO WORK WITH ONE OF 535 00:18:25,600 --> 00:18:28,400 MY COLLEAGUES FROM STANFORD, DRE 536 00:18:28,400 --> 00:18:29,720 HEARING FROM HIM SHORTLY AND I 537 00:18:29,720 --> 00:18:31,360 HOPE HE WILL FILL IN SOME OF THE 538 00:18:31,360 --> 00:18:32,520 DETAIL I DON'T HAVE TIME TO TALK 539 00:18:32,520 --> 00:18:34,080 ABOUT, BUT WHAT WE DETERMINED IN 540 00:18:34,080 --> 00:18:36,600 OUR SUBSEQUENT WORK AS WE TRIED 541 00:18:36,600 --> 00:18:40,080 TO LOOK AT THE 5-LO PATHWAY IS 542 00:18:40,080 --> 00:18:42,080 THAT IN FACT IT IS THE 5-LO 543 00:18:42,080 --> 00:18:42,920 PATHWAY THAT SEEMS TO BE THE 544 00:18:42,920 --> 00:18:45,040 AGENT OF INTEREST IN THE 545 00:18:45,040 --> 00:18:46,120 TREATMENT RESPONSE, AND WHAT WE 546 00:18:46,120 --> 00:18:49,560 WERE ABLE TO SHOW IS THAT WHEN 547 00:18:49,560 --> 00:18:51,200 WE SPECIFICALLY BLOCKED A 548 00:18:51,200 --> 00:18:53,400 DOWNSTREAM MEDIATOR FROM 5-LO 549 00:18:53,400 --> 00:18:56,360 ACTIVATION WHICH IS CALLED LTB4, 550 00:18:56,360 --> 00:18:58,880 WE FOUND THAT WE COULD REVERT 551 00:18:58,880 --> 00:19:04,560 WHAT AMOUNTS TO A MOUSE TAIL 552 00:19:04,560 --> 00:19:06,000 LYMPHOSCINTOGRAM FROM ITS NORMAL 553 00:19:06,000 --> 00:19:08,520 PATTERN BACK TO A NEARLY NORMAL 554 00:19:08,520 --> 00:19:10,240 PATTERN WITH JUST AS LITTLE AS 555 00:19:10,240 --> 00:19:12,240 ONE WEEK OF EXPOSURE TO A 556 00:19:12,240 --> 00:19:15,840 SYSTEMIC ANTAGONIST OF THE 557 00:19:15,840 --> 00:19:17,480 ENZYMATIC PROCESS SO THIS IS 558 00:19:17,480 --> 00:19:18,480 UNTREATED LYMPHEDEMA WITH HUGE 559 00:19:18,480 --> 00:19:20,000 LAKES OF INTERSTITIAL FLUID 560 00:19:20,000 --> 00:19:22,520 EQUIVALENT TO THE DERMAL BACK 561 00:19:22,520 --> 00:19:25,240 FLOW WE SEE BACK TO A NEARLY 562 00:19:25,240 --> 00:19:25,720 NORMAL PATTERN. 563 00:19:25,720 --> 00:19:27,560 JUST TO SHOW YOU THAT THIS IS 564 00:19:27,560 --> 00:19:30,600 NOT JUST A MICROVASCULAR 565 00:19:30,600 --> 00:19:32,360 PHENOMENON, IN COLLABORATION 566 00:19:32,360 --> 00:19:34,800 WITH DR. BRANDON DIXON, WE 567 00:19:34,800 --> 00:19:42,080 ACTUALLY PERFORMED ICG 568 00:19:42,080 --> 00:19:43,080 LYMPHOGRAPHY AND WHAT YOU SEE 569 00:19:43,080 --> 00:19:44,200 PRIOR TO THE SITE OF SURGICAL 570 00:19:44,200 --> 00:19:46,080 ABLATION, YOU WILL SEE RETURN OF 571 00:19:46,080 --> 00:19:47,120 FLOW THROUGH THE MAJOR 572 00:19:47,120 --> 00:19:49,000 COLLECTING VESSEL THAT LEADS 573 00:19:49,000 --> 00:19:50,080 BACK TO THE ANIMAL. 574 00:19:50,080 --> 00:19:51,320 I WON'T TAKE THE TIME TO SHOW 575 00:19:51,320 --> 00:19:53,360 YOU THE SALINE CONTROL, EXCEPT 576 00:19:53,360 --> 00:19:58,840 TO SAY THAT IN FACT WE SEE NO 577 00:19:58,840 --> 00:19:59,600 SIMILAR VISUALIZATION. 578 00:19:59,600 --> 00:20:01,240 SO WHAT WE LEARNED FROM THIS 579 00:20:01,240 --> 00:20:02,760 ANALYSIS IS THAT HOW YOU BLOCK 580 00:20:02,760 --> 00:20:04,760 INFLAMMATION HAS A TREMENDOUS 581 00:20:04,760 --> 00:20:08,440 IMPACT ON WHETHER OR NOT YOU CAN 582 00:20:08,440 --> 00:20:10,320 IMPROVE THE MICRO HISTOLOGY AND 583 00:20:10,320 --> 00:20:14,400 THE FUNCTION IN THE DISEASED 584 00:20:14,400 --> 00:20:14,680 ANIMAL. 585 00:20:14,680 --> 00:20:17,400 SO WHAT WE LEARNED IN GENERAL IS 586 00:20:17,400 --> 00:20:18,880 THAT 5-LO OR ANY OF THE AGENTS 587 00:20:18,880 --> 00:20:21,920 THAT COULD BLOCK LTB4 EXPRESSION 588 00:20:21,920 --> 00:20:23,760 WERE SUCCESSFUL IN IMPROVING 589 00:20:23,760 --> 00:20:25,440 TAIL VOLUME AND ALL THE OTHER 590 00:20:25,440 --> 00:20:26,320 ATTRIBUTES OF DISEASE BUT ALL 591 00:20:26,320 --> 00:20:28,360 THE OTHER PATHWAYS WERE NEGATIVE 592 00:20:28,360 --> 00:20:31,720 INCLUDING DIRECT INHIBITION OF 593 00:20:31,720 --> 00:20:32,120 CYCLOOXYGENASE. 594 00:20:32,120 --> 00:20:34,160 WE ALSO SAMPLED LTB4 IN THE 595 00:20:34,160 --> 00:20:37,480 SERUM OF THE MICE AND WE DID A 596 00:20:37,480 --> 00:20:38,560 SIMILAR ANALYSIS IN LYMPHEDEMA 597 00:20:38,560 --> 00:20:39,760 HUMAN SUBJECTS COMPARING THEM TO 598 00:20:39,760 --> 00:20:41,400 HEALTHY CONTROLS, AND IN BOTH 599 00:20:41,400 --> 00:20:43,480 CASES, THERE IS DRAMATIC 600 00:20:43,480 --> 00:20:45,560 INCREASE IN THE DETECTABLE 601 00:20:45,560 --> 00:20:47,280 CONCENTRATIONS OF THIS 602 00:20:47,280 --> 00:20:48,280 INFLAMMATORY MEDIATOR WITHIN THE 603 00:20:48,280 --> 00:20:49,040 SERUM. 604 00:20:49,040 --> 00:20:51,120 SO THIS LED US TO BELIEVE, AND 605 00:20:51,120 --> 00:20:53,320 WE CONTINUE TO BELIEVE THAT, IN 606 00:20:53,320 --> 00:20:56,680 FACT, LTB4 IS THE AGENT THAT IS 607 00:20:56,680 --> 00:21:00,880 DRIVING THE PROGRESSION FROM 608 00:21:00,880 --> 00:21:01,880 LYMPHEDEMA TO THE PATHOLOGY AT 609 00:21:01,880 --> 00:21:05,360 THE TISSUE LEVEL. 610 00:21:05,360 --> 00:21:06,560 LTB4 IS A VERY POTENT AGENT, I 611 00:21:06,560 --> 00:21:07,880 DON'T HAVE TIME TO TALK ABOUT IT 612 00:21:07,880 --> 00:21:09,840 IN DETAIL HERE, BUT WE CONTINUE 613 00:21:09,840 --> 00:21:12,400 TO BE VERY INTERESTED IN IT. 614 00:21:12,400 --> 00:21:17,720 WE NEXT WENT ON TO LAUNCH A 615 00:21:17,720 --> 00:21:18,840 PLACEBO CONTROL TRIAL LOOKING AT 616 00:21:18,840 --> 00:21:19,880 LYMPHEDEMA IN THE LEG IN BOTH 617 00:21:19,880 --> 00:21:20,880 PRIMARY AND SECONDARY 618 00:21:20,880 --> 00:21:23,000 LYMPHEDEMA, IN WHICH WE USED THE 619 00:21:23,000 --> 00:21:25,880 SAME LTB4 ANTAGONIST THAT WAS 620 00:21:25,880 --> 00:21:29,800 USED IN THE MURINE STUDIES. 621 00:21:29,800 --> 00:21:34,760 THIS AGENT, UBENIMEX IS AN AMINO 622 00:21:34,760 --> 00:21:36,320 PEPTIDASE THAT HAS THE ABILITY 623 00:21:36,320 --> 00:21:37,840 TO BLOCK A VARIETY OF PROTEIN 624 00:21:37,840 --> 00:21:39,040 ACTIONS INCLUDING THE ENZYME OF 625 00:21:39,040 --> 00:21:41,760 INTEREST THAT WE WERE LOOKING 626 00:21:41,760 --> 00:21:41,960 AT. 627 00:21:41,960 --> 00:21:43,160 UNFORTUNATELY, I CONTINUE TO GET 628 00:21:43,160 --> 00:21:45,720 ASKED THIS QUESTION ON A 629 00:21:45,720 --> 00:21:46,480 WEEK-BY-WEEK BASIS, WE DID HAVE 630 00:21:46,480 --> 00:21:48,880 TO TERMINATE THE STUDY FOR 631 00:21:48,880 --> 00:21:51,520 FUNDING REASONS BEFORE WE 632 00:21:51,520 --> 00:21:53,240 REACHED THE ENROLLMENT THAT WAS 633 00:21:53,240 --> 00:21:54,680 PREDICTED BY SAMPLE SIZE 634 00:21:54,680 --> 00:21:56,760 CALCULATION, WE NEEDED TO STUDY 635 00:21:56,760 --> 00:21:59,280 250 SUBJECTS, WE GOT TO STUDY 636 00:21:59,280 --> 00:22:00,800 ONLY 50, SO WE REALLY ARE NOT 637 00:22:00,800 --> 00:22:03,000 ABLE TO ANALYZE THE PRIMARY END 638 00:22:03,000 --> 00:22:05,520 POINT, BUT JUST TO TANTALIZE YOU 639 00:22:05,520 --> 00:22:08,240 INTO WHAT WE SAW IN SOME OF THE 640 00:22:08,240 --> 00:22:09,320 EXPERIMENTAL AGENT RECIPIENTS, 641 00:22:09,320 --> 00:22:11,120 HERE IS ONE OF THE LAST PATIENTS 642 00:22:11,120 --> 00:22:15,440 WE ENROLLED IN THE STUDY, WHO 643 00:22:15,440 --> 00:22:17,200 HAD VERY ADVANCED LYMPHEDEMA OF 644 00:22:17,200 --> 00:22:19,720 A SINGLE LIMB BASED ON CANCER 645 00:22:19,720 --> 00:22:20,800 THERAPEUTICS, AND YOU CAN SEE 646 00:22:20,800 --> 00:22:22,240 WHAT HER LEG LOOKED LIKE PRIOR 647 00:22:22,240 --> 00:22:23,640 TO ENROLLMENT IN THE STUDY. 648 00:22:23,640 --> 00:22:25,800 SHE RECEIVED THE DRUG IN A 649 00:22:25,800 --> 00:22:28,640 DOUBLE BLIND FASHION FOR SIX 650 00:22:28,640 --> 00:22:30,000 MONTHS, LATER UNBLINDED, AND SHE 651 00:22:30,000 --> 00:22:32,520 SENT ME THE PHOTOGRAPH ON THE 652 00:22:32,520 --> 00:22:33,280 RIGHT 18 MONTHS AFTER SHE 653 00:22:33,280 --> 00:22:35,520 STOPPED THE DRUG, AND YOU CAN 654 00:22:35,520 --> 00:22:37,880 SEE THE PERSISTENT AND VERY 655 00:22:37,880 --> 00:22:38,960 DRAMATIC IMPROVEMENT IN THE 656 00:22:38,960 --> 00:22:41,160 APPEARANCE OF HER LIMB BASED 657 00:22:41,160 --> 00:22:43,760 UPON THE EXPOSURE TO THE DRUG 658 00:22:43,760 --> 00:22:44,680 AND NO OTHER SPECIFIC 659 00:22:44,680 --> 00:22:49,480 INTERVENTION. 660 00:22:49,480 --> 00:22:50,560 SO LET ME TELL YOU BRIEFLY ABOUT 661 00:22:50,560 --> 00:22:52,200 THE NEXT ITERATION OF THIS 662 00:22:52,200 --> 00:22:53,520 JOURNEY WHICH WE HAVE JUST 663 00:22:53,520 --> 00:22:54,480 LAUNCHED AND WE HOPE WILL LEAD 664 00:22:54,480 --> 00:22:55,920 US TO THE DEFINITIVE TRIAL. 665 00:22:55,920 --> 00:22:57,800 WE ARE NOW LOOKING AT A MUCH 666 00:22:57,800 --> 00:23:03,440 MORE SPECIFIC ANTAGONIST OF LTBD 667 00:23:03,440 --> 00:23:03,920 ACEBILUSTAT. 668 00:23:03,920 --> 00:23:05,640 HERE YOU SEE THE MOLECULE 669 00:23:05,640 --> 00:23:06,080 DEPICTED. 670 00:23:06,080 --> 00:23:07,880 IT'S AN ORALLY BIOAVAILABLE 671 00:23:07,880 --> 00:23:10,600 SMALL MOLECULE AND IT HAS THE 672 00:23:10,600 --> 00:23:14,120 ABILITY TO BLOCK LEUKOTRIENE 673 00:23:14,120 --> 00:23:16,160 A4 HYDROLASE, THE ENZYME THAT 674 00:23:16,160 --> 00:23:18,720 PRODUCES LTB4, A POTENTIAL 675 00:23:18,720 --> 00:23:19,760 ANTI-INFLAMMATORY AGENT THAT 676 00:23:19,760 --> 00:23:21,400 SPECIFICALLY TARGETS THIS 677 00:23:21,400 --> 00:23:21,840 ENZYME. 678 00:23:21,840 --> 00:23:24,680 IT INHIBITS THE PRODUCTION OF 679 00:23:24,680 --> 00:23:26,880 LTB4 AND THEN WE HOPE THAT IT 680 00:23:26,880 --> 00:23:30,600 WILL HAVE THE INTENDED EFFECT IN 681 00:23:30,600 --> 00:23:31,040 HUMAN LYMPHEDEMA. 682 00:23:31,040 --> 00:23:32,880 AS THOSE OF YOU WHO CONDUCT 683 00:23:32,880 --> 00:23:33,480 CLINICAL TRIALS ALREADY KNOW, 684 00:23:33,480 --> 00:23:35,200 IT'S A COMPLICATED PROCESS. 685 00:23:35,200 --> 00:23:37,280 WE'VE BEEN WORKING WITH THE FDA 686 00:23:37,280 --> 00:23:38,880 AND OTHER REGULATORY AGENCIES 687 00:23:38,880 --> 00:23:40,880 OVER THE LAST 24 MONTHS AND WE 688 00:23:40,880 --> 00:23:42,320 HAVE JUST LAUNCHED THE TRIAL A 689 00:23:42,320 --> 00:23:46,240 COUPLE OF MONTHS AGO AFTER A LOT 690 00:23:46,240 --> 00:23:46,920 OF PREPARATORY WORK. 691 00:23:46,920 --> 00:23:47,680 I'M FORTUNATE TO HAVE THE 692 00:23:47,680 --> 00:23:49,520 SUPPORT OF AN INTERNAL 693 00:23:49,520 --> 00:23:52,480 ORGANIZATION AT STANFORD CALLED 694 00:23:52,480 --> 00:23:55,200 THE INNOVATIVE MEDICINE'S 695 00:23:55,200 --> 00:23:55,960 ACCELERATOR AND RECEIVED 696 00:23:55,960 --> 00:23:57,160 GRANTING THROUGH A COMPETITIVE 697 00:23:57,160 --> 00:23:58,200 PROCESS AND ALSO HAVE RECEIVED 698 00:23:58,200 --> 00:24:01,560 FUNDING FROM THE PHARMACEUTICAL 699 00:24:01,560 --> 00:24:03,600 SPONSOR WHO HOLDS THE RIGHTS TO 700 00:24:03,600 --> 00:24:08,240 THE DRUG CALLED CELLTAXIS. 701 00:24:08,240 --> 00:24:09,440 TO BRIEFLY LET YOU KNOW WHAT 702 00:24:09,440 --> 00:24:11,200 WE'RE DOING, WE'RE LOOKING AT 703 00:24:11,200 --> 00:24:12,480 THIS POINT AT ARM LYMPHEDEMA IN 704 00:24:12,480 --> 00:24:14,960 A SINGLE LIMB PER SUBJECT IN 705 00:24:14,960 --> 00:24:18,640 ORDER TO ACHIEVE AS MUCH 706 00:24:18,640 --> 00:24:19,520 HOMOGENEITY IN THE PATIENT 707 00:24:19,520 --> 00:24:20,160 POPULATION AS POSSIBLE. 708 00:24:20,160 --> 00:24:21,720 I FEEL THAT ARM LYMPHEDEMA HAS 709 00:24:21,720 --> 00:24:27,240 MUCH MORE HOMO JE HOMOGENEIS 710 00:24:27,240 --> 00:24:29,760 COUNTER PART IN THE LEG, GREATER 711 00:24:29,760 --> 00:24:30,920 THAN SIX MONTHS DURATION, THIS 712 00:24:30,920 --> 00:24:33,320 CAN BE MALES OR FEMALES WHO ARE 713 00:24:33,320 --> 00:24:35,360 ADULTS. 714 00:24:35,360 --> 00:24:38,080 THIS IS MEANT TO BE AN OPEN 715 00:24:38,080 --> 00:24:39,880 LABEL OBSERVATION OF THE 716 00:24:39,880 --> 00:24:40,720 ACTIVITY OF THE DRUG. 717 00:24:40,720 --> 00:24:43,320 IN THIS CASE, WE HAVE DECIDED TO 718 00:24:43,320 --> 00:24:45,520 CONTINUE TO LOOK AT DERMAL 719 00:24:45,520 --> 00:24:49,240 ULTRASOUND BY ULTRA SONOGRAPHY 720 00:24:49,240 --> 00:24:50,440 ALTHOUGH WE WILL CONTINUE TO 721 00:24:50,440 --> 00:24:51,840 MEASURE BY CALIPER AS WELL AND 722 00:24:51,840 --> 00:24:53,920 WE WILL HAVE A QUALITY OF 723 00:24:53,920 --> 00:24:55,600 SECONDARY END POINTS INCLUDING 724 00:24:55,600 --> 00:24:58,440 QUALITY OF LIFE AND OARL 725 00:24:58,440 --> 00:24:59,320 MEASURES OF THE DISEASE. 726 00:24:59,320 --> 00:25:00,360 ALL PARTICIPANTS DO RECEIVE 727 00:25:00,360 --> 00:25:01,040 ACTIVE DRUGS. 728 00:25:01,040 --> 00:25:02,120 THEY ARE GOING TO BE FOLLOWED 729 00:25:02,120 --> 00:25:03,480 OVER A NINE MONTH PERIOD OF TIME 730 00:25:03,480 --> 00:25:05,120 AT THREE-MONTH INTERVALS IN A 731 00:25:05,120 --> 00:25:06,960 SINGLE CENTER STUDY HERE AT 732 00:25:06,960 --> 00:25:07,200 STANFORD. 733 00:25:07,200 --> 00:25:09,720 IT IS A NONINVASIVE STUDY, AND 734 00:25:09,720 --> 00:25:12,040 AS I'VE SAID, WE'LL BE MEASURING 735 00:25:12,040 --> 00:25:14,200 DERMAL THICKNESS, BOTH BY 736 00:25:14,200 --> 00:25:15,560 ULTRASOUND AND BY CALIPERS, AND 737 00:25:15,560 --> 00:25:18,920 WE'LL BE DOING MOLECULAR 738 00:25:18,920 --> 00:25:20,080 ANALYSIS AS WELL AS ROUTINE 739 00:25:20,080 --> 00:25:22,600 CHEMICAL ANALYSIS TO LOOK FOR 740 00:25:22,600 --> 00:25:26,640 ANY POTENTIAL FOR TOXICITY. 741 00:25:26,640 --> 00:25:27,320 I'VE ALREADY MENTIONED THE 742 00:25:27,320 --> 00:25:28,320 DURATION OF GREATER THAN SIX 743 00:25:28,320 --> 00:25:28,720 MONTHS. 744 00:25:28,720 --> 00:25:29,920 WE WILL WORK WITH PATIENTS WHO 745 00:25:29,920 --> 00:25:32,360 HAVE HAD PRIOR MICROVASCULAR 746 00:25:32,360 --> 00:25:33,000 INTERVENTIONS PROVIDED THAT 747 00:25:33,000 --> 00:25:36,080 THEY'VE HAD AT LEAST ONE YEAR 748 00:25:36,080 --> 00:25:37,360 SINCE THEIR SURGICAL 749 00:25:37,360 --> 00:25:38,240 INTERVENTION, AND THAT THEY 750 00:25:38,240 --> 00:25:41,400 CONTINUE TO HAVE SUITABLE 751 00:25:41,400 --> 00:25:44,920 MEASURABLE MANIFESTATIONS OF THE 752 00:25:44,920 --> 00:25:45,360 DISEASE. 753 00:25:45,360 --> 00:25:47,600 WE WILL CONTINUE ALL USUAL 754 00:25:47,600 --> 00:25:48,080 INTERVENTIONS FOR THE 755 00:25:48,080 --> 00:25:49,840 LYMPHEDEMA, ALL THE PHYSICAL 756 00:25:49,840 --> 00:25:51,160 INTERVENTIONS, AND WITHOUT 757 00:25:51,160 --> 00:25:52,360 ADDITION OF ANY MAINTENANCE 758 00:25:52,360 --> 00:25:53,320 MODALITIES DURING THE NINE 759 00:25:53,320 --> 00:25:57,080 MONTHS OF OBSERVATION, AND WE 760 00:25:57,080 --> 00:25:58,920 WILL NOT BE ABLE TO DEAL WITH 761 00:25:58,920 --> 00:26:00,560 PATIENTS WHO WILL HAVE SURGICAL 762 00:26:00,560 --> 00:26:01,240 INTERVENTION, OF COURSE, DURING 763 00:26:01,240 --> 00:26:02,760 THE STUDY. 764 00:26:02,760 --> 00:26:04,880 AND WE WILL EXCLUDE ANY OTHER 765 00:26:04,880 --> 00:26:07,760 MEDICAL CONDITIONS THAT PRODUCE 766 00:26:07,760 --> 00:26:08,280 LYMPHEDEMA. 767 00:26:08,280 --> 00:26:09,880 SO WITH THAT, I HOPE TO COME 768 00:26:09,880 --> 00:26:11,360 BACK AT SOME POINT IN THE NEAR 769 00:26:11,360 --> 00:26:15,120 FUTURE AND TELL YOU THAT WE 770 00:26:15,120 --> 00:26:16,080 INDEED SUCCEEDED AND WE CAN GO 771 00:26:16,080 --> 00:26:18,240 ON TO A FULL PLACEBO CONTROLLED 772 00:26:18,240 --> 00:26:18,480 TRIAL. 773 00:26:18,480 --> 00:26:19,680 I WANT TO ACKNOWLEDGE MY SOURCES 774 00:26:19,680 --> 00:26:20,560 OF FUNDING. 775 00:26:20,560 --> 00:26:24,520 I WANT TO ACKNOWLEDGE ALL OF MY 776 00:26:24,520 --> 00:26:25,480 INCREDIBLE COLLABORATORS OVER 777 00:26:25,480 --> 00:26:32,320 THE YEARS, INCLUDING DR. NICOLLS 778 00:26:32,320 --> 00:26:41,560 AND DR. ME MEHRARA. 779 00:26:41,560 --> 00:26:42,560 SOME OF THEM ARE STILL AROUND 780 00:26:42,560 --> 00:26:43,200 AND WITH ME. 781 00:26:43,200 --> 00:26:45,520 I ALSO WANT TO ESPECIALLY 782 00:26:45,520 --> 00:26:47,200 ACKNOWLEDGE ONE SCIENTIST WHO 783 00:26:47,200 --> 00:26:49,000 WORKED WITH US IN AN 784 00:26:49,000 --> 00:26:50,160 EXTRAORDINARY FASHION ON THE 785 00:26:50,160 --> 00:26:52,520 MURINE STUDIES RELATED TO LTB4. 786 00:26:52,520 --> 00:26:54,040 AMY IS A PHENOMENAL SCIENTIST 787 00:26:54,040 --> 00:26:55,360 AND I'M PROUD TO SAY THAT THIS 788 00:26:55,360 --> 00:26:57,640 WORK WON HER AN AWARD AT THE 789 00:26:57,640 --> 00:27:00,080 FIRST ITERATION OF THE LYMPHATIC 790 00:27:00,080 --> 00:27:00,520 FORUM CONFERENCE. 791 00:27:00,520 --> 00:27:01,840 HERE SHE IS IN FRONT OF HER 792 00:27:01,840 --> 00:27:02,880 POSTER. 793 00:27:02,880 --> 00:27:05,640 SO JUST TO SUMMARIZE THE 794 00:27:05,640 --> 00:27:07,000 QUESTIONS THAT REMAIN, OF 795 00:27:07,000 --> 00:27:08,480 COURSE, WILL THE DRUG WORK, IS 796 00:27:08,480 --> 00:27:10,680 THERE A ROLE FOR PHARMACOLOGY 797 00:27:10,680 --> 00:27:13,400 AND LYMPHEDEMA PREVENTION? 798 00:27:13,400 --> 00:27:14,960 DO WE HAVE A ROLE FOR THIS 799 00:27:14,960 --> 00:27:17,240 SIMILAR PATHWAY IN OTHER 800 00:27:17,240 --> 00:27:19,080 ITERATIONS OF LYMPHATIC DISEASE, 801 00:27:19,080 --> 00:27:25,240 INCLUDING VASCULAR 802 00:27:25,240 --> 00:27:26,080 MALFORMATIONS, LIPEDEMA AND 803 00:27:26,080 --> 00:27:26,760 OTHERS? 804 00:27:26,760 --> 00:27:31,560 HOW DOES LEUKOTREEN ACTIVATION 805 00:27:31,560 --> 00:27:33,440 RELATE TO -- WHICH OF COURSE 806 00:27:33,440 --> 00:27:34,840 WILL PROBABLY BE A SLOWER 807 00:27:34,840 --> 00:27:38,440 RESPONSE PROCESS, AND HOW DOES 808 00:27:38,440 --> 00:27:40,200 LEUKOTRIENE ACTIVATION RELATE TO 809 00:27:40,200 --> 00:27:41,360 DOWNSTREAM CYTOKINE ACTIVATION 810 00:27:41,360 --> 00:27:42,720 AND ARE THERE OTHER TARGETED 811 00:27:42,720 --> 00:27:43,160 OPPORTUNITIES? 812 00:27:43,160 --> 00:27:45,120 SO IN SUMMARY, I WANT TO BELIEVE 813 00:27:45,120 --> 00:27:47,760 THAT ANYTHING IS POSSIBLE. 814 00:27:47,760 --> 00:27:48,760 IT'S STILL HARD FOR ME TO 815 00:27:48,760 --> 00:27:49,840 BELIEVE THAT WE'VE COME THIS 816 00:27:49,840 --> 00:27:51,560 FAR, BUT WE'RE NOT DONE YET AND 817 00:27:51,560 --> 00:27:52,920 WE HOPE THERE WILL BE GREATER 818 00:27:52,920 --> 00:27:54,000 SUCCESSES IN THE FUTURE. 819 00:27:54,000 --> 00:27:55,280 SO THANKS VERY MUCH FOR THE 820 00:27:55,280 --> 00:28:03,400 OPPORTUNITY TO SPEAK TO YOU THIS 821 00:28:03,400 --> 00:28:03,640 MORNING. 822 00:28:03,640 --> 00:28:05,560 >> THANK YOU, DR. ROCKSON. 823 00:28:05,560 --> 00:28:06,040 THAT WAS FANTASTIC. 824 00:28:06,040 --> 00:28:07,200 I THINK IN THE INTEREST OF TIME, 825 00:28:07,200 --> 00:28:08,520 WE'RE GOING TO TAKE QUESTIONS 826 00:28:08,520 --> 00:28:11,480 FROM DR. ROCKSON AT THE END OF 827 00:28:11,480 --> 00:28:12,480 SESSION FIVE AND INCLUDE THAT IN 828 00:28:12,480 --> 00:28:16,720 THERE, IF THAT'S OKAY WITH YOU. 829 00:28:16,720 --> 00:28:18,240 >> YES, THANKS SO MUCH. 830 00:28:18,240 --> 00:28:18,640 >> GREAT. 831 00:28:18,640 --> 00:28:20,160 THANK YOU SO MUCH, STAN. 832 00:28:20,160 --> 00:28:21,360 THAT WAS REALLY LOVELY. 833 00:28:21,360 --> 00:28:22,440 WE'LL KEEP OUR FINGERS CROSSED 834 00:28:22,440 --> 00:28:24,280 FOR THE CLINICAL TRIAL. 835 00:28:24,280 --> 00:28:26,280 SO NOW IT'S MY PLEASURE AND 836 00:28:26,280 --> 00:28:29,200 DELIGHT TO INTRODUCE DR. SARAH 837 00:28:29,200 --> 00:28:31,520 TEICHMANN, THE CO-FOUNDER AND 838 00:28:31,520 --> 00:28:32,920 PRINCIPAL LEADER OF THE HUMAN 839 00:28:32,920 --> 00:28:34,440 CELL ATLAS, INTERNATIONAL 840 00:28:34,440 --> 00:28:39,360 CONSORTIUM AND HEAD OF CELLULAR 841 00:28:39,360 --> 00:28:42,280 GENETICS AT THE WELLCOME SANGER 842 00:28:42,280 --> 00:28:42,560 INSTITUTE. 843 00:28:42,560 --> 00:28:43,880 THE TITLE OF HER SPECIAL 844 00:28:43,880 --> 00:28:45,800 INTEREST TALK IS "MAPPING THE 845 00:28:45,800 --> 00:28:47,720 HUMAN BODY ONE CELL AT A TIME." 846 00:28:47,720 --> 00:28:49,240 AND I KNOW THE LYMPHATIC FIELD 847 00:28:49,240 --> 00:28:52,000 WILL BENEFIT FROM HER EXPERTISE 848 00:28:52,000 --> 00:28:54,160 IN DEFINING CELLS AND SINGLE 849 00:28:54,160 --> 00:28:55,360 CELL RESOLUTION IN DIVERSE 850 00:28:55,360 --> 00:28:57,240 ORGANS, INCLUDING LYMPHOID 851 00:28:57,240 --> 00:28:57,760 ORGANS. 852 00:28:57,760 --> 00:28:59,320 SO SARAH, IF YOU CAN SHARE YOUR 853 00:28:59,320 --> 00:29:00,400 SCREEN, THERE YOU GO. 854 00:29:00,400 --> 00:29:00,960 IT'S ALL YOURS. 855 00:29:00,960 --> 00:29:01,960 THANK YOU, SARAH. 856 00:29:01,960 --> 00:29:04,000 >> THANK YOU, ANDREA, FOR THAT 857 00:29:04,000 --> 00:29:04,560 KIND INTRODUCTION. 858 00:29:04,560 --> 00:29:06,280 I HOPE YOU CAN SEE THIS AND HEAR 859 00:29:06,280 --> 00:29:11,880 ME WELL. 860 00:29:11,880 --> 00:29:13,800 FANTASTIC. 861 00:29:13,800 --> 00:29:15,080 AS ANDREA SAID, THE APPROACH 862 00:29:15,080 --> 00:29:17,360 THAT WE'VE BEEN TAKING IN THE 863 00:29:17,360 --> 00:29:18,480 HUMAN CELL IN THIS COMMUNITY IS 864 00:29:18,480 --> 00:29:20,200 MAPPING THE CELLS IN THE HUMAN 865 00:29:20,200 --> 00:29:20,920 BODY. 866 00:29:20,920 --> 00:29:24,920 AND THE IDEA HERE GOES BACK OVER 867 00:29:24,920 --> 00:29:29,280 20 YEARS, AND WHAT I'M CITING 868 00:29:29,280 --> 00:29:33,560 HERE IS FROM SYDNEY BRENNER 869 00:29:33,560 --> 00:29:35,000 WHERE HE SAYS WE NEED A PROGRAM 870 00:29:35,000 --> 00:29:37,480 OF MAKING MAPS OF CELLS AND MAPS 871 00:29:37,480 --> 00:29:39,680 OF HOW CELLS TALK TO EACH OTHER. 872 00:29:39,680 --> 00:29:41,120 THE CELLMAP PROJECT FOR WHICH WE 873 00:29:41,120 --> 00:29:42,560 DON'T NEED A MODEL ORGANISM, IN 874 00:29:42,560 --> 00:29:44,400 OTHER WORDS WE CAN JUST STUDY 875 00:29:44,400 --> 00:29:46,600 THE HUMAN BODY AS OPPOSED TO 876 00:29:46,600 --> 00:29:48,320 MOUSE, FISH, SO ON, WILL BE ONE 877 00:29:48,320 --> 00:29:49,880 OF THE THINGS TO OCCUPY US FOR 878 00:29:49,880 --> 00:29:50,960 THE NEXT FEW DECADES. 879 00:29:50,960 --> 00:29:52,480 SO THIS IDEA WE NEED TO 880 00:29:52,480 --> 00:29:53,520 UNDERSTAND THE MOLECULAR AND 881 00:29:53,520 --> 00:29:55,440 CELLULAR BASIS OF THE HUMAN 882 00:29:55,440 --> 00:30:01,760 BODY, YOU KNOW, IS IMPORTANT 883 00:30:01,760 --> 00:30:03,400 CLEARLY FOR BIOMEDICAL RESEARCH 884 00:30:03,400 --> 00:30:07,800 AND SORT OF CAME TO FRUITION, 885 00:30:07,800 --> 00:30:09,880 REALLY, WITH TECHNOLOGIES THAT 886 00:30:09,880 --> 00:30:11,840 HAVE ADVANCED OUR ABILITY TO 887 00:30:11,840 --> 00:30:13,040 STUDY CELLS IN A QUANTITATIVE 888 00:30:13,040 --> 00:30:14,440 WAY. 889 00:30:14,440 --> 00:30:16,440 AND IT WAS THAT, THE SINGLE CELL 890 00:30:16,440 --> 00:30:18,080 GENOMICS AND SPATIAL GENOMICS 891 00:30:18,080 --> 00:30:22,320 TECHNOLOGIES THAT GAVE THE -- 892 00:30:22,320 --> 00:30:24,880 REALLY BUOYED THE IDEA OF AN 893 00:30:24,880 --> 00:30:25,720 INTERNATIONAL HUMAN CELLS 894 00:30:25,720 --> 00:30:26,080 CONSORTIUM. 895 00:30:26,080 --> 00:30:26,920 THE MISSION OF THIS 896 00:30:26,920 --> 00:30:27,800 INTERNATIONAL PROJECT IS TO 897 00:30:27,800 --> 00:30:29,920 CREATE A COMPREHENSIVE REFERENCE 898 00:30:29,920 --> 00:30:33,600 MAP OF OUR CELLS AND THAT'S BOTH 899 00:30:33,600 --> 00:30:36,440 FROM THE POINT OF VIEW OF 900 00:30:36,440 --> 00:30:37,760 CURIOSITY-DRIVEN BASIC SCIENCE 901 00:30:37,760 --> 00:30:40,800 AS WELL AS APPLICATIONS TO 902 00:30:40,800 --> 00:30:47,800 DIAGNOSTICS AND TREATS DISEASE. 903 00:30:47,800 --> 00:30:52,760 JUST TO SET THE XENO, SCENE,E 904 00:30:52,760 --> 00:30:54,920 LIVED THROUGH A REVOLUTION IN 905 00:30:54,920 --> 00:30:56,360 GENOMICS WHERE WE'RE ABLE TO 906 00:30:56,360 --> 00:30:58,080 SEQUENCE THE NUCLEIC CONTENTS OF 907 00:30:58,080 --> 00:31:00,640 INDIVIDUAL KELS CELLS, AND, 908 00:31:00,640 --> 00:31:02,280 THEREFORE, DESCRIBE THE CELL 909 00:31:02,280 --> 00:31:06,440 TYPES AND CELL STATES IN A 910 00:31:06,440 --> 00:31:07,080 TISSUE SAMPLE. 911 00:31:07,080 --> 00:31:09,040 I HAVE A SAMPLE OF THE HEART 912 00:31:09,040 --> 00:31:11,480 HERE, IN TERMS OF THE GENOMIC 913 00:31:11,480 --> 00:31:14,400 CONTENT OF THE CELLS OR THEIR 914 00:31:14,400 --> 00:31:15,760 NUCLEON. 915 00:31:15,760 --> 00:31:17,040 THEIR MOST COMMON MODALITY 916 00:31:17,040 --> 00:31:19,560 MEASURE IS RNA, REFLECTING THE 917 00:31:19,560 --> 00:31:23,480 GENES THAT ARE EXPRESSED IN 918 00:31:23,480 --> 00:31:24,920 CELLS' NUCLEI AND AMPLIFIED BY 919 00:31:24,920 --> 00:31:25,480 TRANSCRIPTION. 920 00:31:25,480 --> 00:31:27,000 WHAT THIS ALLOWS US TO DO IS 921 00:31:27,000 --> 00:31:30,920 THEN ANALYZE THAT HIGH 922 00:31:30,920 --> 00:31:33,240 DIMENSIONAL DATA AND EXPRESS 923 00:31:33,240 --> 00:31:35,520 GENES AS A MATRIX AND DEFINE 924 00:31:35,520 --> 00:31:36,200 INDIVIDUAL CELL STATES WHICH ARE 925 00:31:36,200 --> 00:31:38,360 KIND OF REFLECTED IN THIS 926 00:31:38,360 --> 00:31:40,000 TWO-DIMENSIONAL SPACE BY USING 927 00:31:40,000 --> 00:31:43,520 COMPUTATIONAL METHODS. 928 00:31:43,520 --> 00:31:45,040 THE SINGLE CELL OR SINGLE 929 00:31:45,040 --> 00:31:47,800 NUCLEAR TECHNOLOGIES HAVE KIND 930 00:31:47,800 --> 00:31:49,880 OF ADVANCED A PACE AND IN 931 00:31:49,880 --> 00:31:54,120 PARALLEL, WE'VE HAD SPATIAL 932 00:31:54,120 --> 00:31:57,200 GENOMICS, SPATIAL 933 00:31:57,200 --> 00:32:00,080 TRANSCRIPTOMICS TECHNOLOGIES 934 00:32:00,080 --> 00:32:03,240 RUNNING FOR US AT THE SAME TIME 935 00:32:03,240 --> 00:32:06,080 AND THERE ARE DIFFERENT 936 00:32:06,080 --> 00:32:07,920 APPROACHES HERE. 937 00:32:07,920 --> 00:32:09,000 SEQUENCING-BASED APPROACHES TO 938 00:32:09,000 --> 00:32:11,080 SORT OF MAP THE GEOGRAPHY OF THE 939 00:32:11,080 --> 00:32:12,160 TRANSCRIPTOME OF THE TISSUE 940 00:32:12,160 --> 00:32:14,560 SECTION AND THEN IMAGING-BASED, 941 00:32:14,560 --> 00:32:17,800 WHICH IS HIGH DIMENSIONAL 942 00:32:17,800 --> 00:32:19,600 MICROSCOPY OF RNA OR OF PROTEIN 943 00:32:19,600 --> 00:32:24,400 AND, OF COURSE -- WHO INTRODUCED 944 00:32:24,400 --> 00:32:26,960 ME IS ONE OF THE DEVELOPERS 945 00:32:26,960 --> 00:32:28,240 OF -- PROTEIN IMAGING. 946 00:32:28,240 --> 00:32:29,640 I WON'T TALK ABOUT THIS SO MUCH 947 00:32:29,640 --> 00:32:30,240 IN MY TALK. 948 00:32:30,240 --> 00:32:33,080 WHAT I WANT TO FOCUS ON IS 949 00:32:33,080 --> 00:32:34,400 ONGOING PROJECT IN MY LAB, WHICH 950 00:32:34,400 --> 00:32:35,880 IS UNPUBLISHED AND I'M SHARING 951 00:32:35,880 --> 00:32:38,320 THIS WITH YOU HERE IN A SORT OF 952 00:32:38,320 --> 00:32:41,080 UNFINISHED STATE, WHERE WE ARE 953 00:32:41,080 --> 00:32:47,960 BASICALLY TAKING TOGETHER 954 00:32:47,960 --> 00:32:49,160 PUBLISHED DATASETS FROM THE 955 00:32:49,160 --> 00:32:50,480 COMMUNITY INCLUDING MY OWN GROUP 956 00:32:50,480 --> 00:32:52,480 AND SOME UNPUBLISHED DATA TO 957 00:32:52,480 --> 00:32:54,800 CREATE OR TO SORT OF ASSEMBLE AN 958 00:32:54,800 --> 00:32:58,280 OVERVIEW OF THE VASCULATURE IN 959 00:32:58,280 --> 00:32:59,840 OUR BODY, AND THAT INCLUDES THE 960 00:32:59,840 --> 00:33:02,840 BLOOD VESSELS AND THE LYMPHATIC 961 00:33:02,840 --> 00:33:04,640 VESSELS AND THEN RELATE THE 962 00:33:04,640 --> 00:33:07,240 DIFFERENT CELL STATES TO DISEASE 963 00:33:07,240 --> 00:33:07,920 ASSOCIATIONS AND SO ON. 964 00:33:07,920 --> 00:33:09,800 I JUST WANT TO GIVE YOU A 965 00:33:09,800 --> 00:33:13,160 FEELING FOR HOW THE HUMAN CELL 966 00:33:13,160 --> 00:33:16,920 IN THIS DATA CAN START 967 00:33:16,920 --> 00:33:18,200 CONTRIBUTING TO THE 968 00:33:18,200 --> 00:33:19,320 UNDERSTANDING OF OUR 969 00:33:19,320 --> 00:33:22,480 VASCULATURE. 970 00:33:22,480 --> 00:33:24,560 AND I THINK THIS IS A REALLY 971 00:33:24,560 --> 00:33:25,640 EXCITING JUNCTURE IN THE PROJECT 972 00:33:25,640 --> 00:33:27,280 BECAUSE WE'VE NOW, AS A 973 00:33:27,280 --> 00:33:28,920 COMMUNITY, YOU KNOW, ACROSS THE 974 00:33:28,920 --> 00:33:31,320 WORLD GENERATED ENOUGH DATA THAT 975 00:33:31,320 --> 00:33:32,560 WE'RE SORT OF AT THE POINT WHERE 976 00:33:32,560 --> 00:33:36,480 WE CAN START ASSEMBLING A DRAFT 977 00:33:36,480 --> 00:33:40,000 OF THE HUMAN -- A FIRST DRAFT OF 978 00:33:40,000 --> 00:33:45,000 THE CELLS IN THE HUMAN BODY, AND 979 00:33:45,000 --> 00:33:46,120 START TAKING A STEP BACK AND 980 00:33:46,120 --> 00:33:47,960 LOOKING ACROSS THE DIFFERENT 981 00:33:47,960 --> 00:33:50,360 ORGANS AND TISSUES AND GET AN 982 00:33:50,360 --> 00:33:52,360 OVERVIEW OF DISTRIBUTED SYSTEMS 983 00:33:52,360 --> 00:33:56,400 LIKE THE VASCULATURE SYSTEM AND 984 00:33:56,400 --> 00:33:57,080 SO ON. 985 00:33:57,080 --> 00:34:00,240 SO IN THE NEXT FEW MINUTES, I'LL 986 00:34:00,240 --> 00:34:04,360 FOCUS ON WORK BY A POSTDOC IN 987 00:34:04,360 --> 00:34:09,000 THE GROUP WORKING TOGETHER WITH 988 00:34:09,000 --> 00:34:09,840 OTHERS WHERE WE'RE STARTING TO 989 00:34:09,840 --> 00:34:13,800 DIG INTO THIS DATA AND MINE IT 990 00:34:13,800 --> 00:34:15,480 AND START TO SEE WHAT WE CAN 991 00:34:15,480 --> 00:34:23,320 LEARN FROM IT. 992 00:34:23,320 --> 00:34:25,320 STATING WHAT'S PROBABLY OBVIOUS 993 00:34:25,320 --> 00:34:26,760 TO EVERYONE IN THE AUDIENCE IS 994 00:34:26,760 --> 00:34:29,360 IN BLOOD VESSELS WE'VE GOT 995 00:34:29,360 --> 00:34:30,680 ENDOTHELIAL CELLS, WHICH ARE 996 00:34:30,680 --> 00:34:32,400 ALSO CONSTITUENTS OF LYMPHATIC 997 00:34:32,400 --> 00:34:33,720 VESSELS, AND THEN IN BLOOD 998 00:34:33,720 --> 00:34:35,040 VESSELS, WE'VE GOT SMOOTH MUSCLE 999 00:34:35,040 --> 00:34:38,200 CELLS AND PARASITES AS WELL. 1000 00:34:38,200 --> 00:34:41,160 AND FOR THE BLOOD VESSELS, WE'VE 1001 00:34:41,160 --> 00:34:43,800 GOT ARTERIES AND ARTERIOLES, 1002 00:34:43,800 --> 00:34:45,880 CAPILLARY, VEINS AND VENULES, 1003 00:34:45,880 --> 00:34:46,760 WHEREAS WITH LYMPHATICS, THE 1004 00:34:46,760 --> 00:34:48,920 MAJOR DIFFERENCES ARE REALLY THE 1005 00:34:48,920 --> 00:34:50,400 VESSELS WITHIN LYMPH NODES AND 1006 00:34:50,400 --> 00:34:53,120 AS COMPARED TO SORT OF 1007 00:34:53,120 --> 00:34:54,440 DISTRIBUTED IN PERIPHERAL 1008 00:34:54,440 --> 00:34:58,920 TISSUES. 1009 00:34:58,920 --> 00:35:01,560 IN A RECENT REVIEW BASICALLY 1010 00:35:01,560 --> 00:35:02,960 THERE'S THIS FIGURE SHOWING THE 1011 00:35:02,960 --> 00:35:03,840 ENDOTHELIAL CELLS THAT ARE KIND 1012 00:35:03,840 --> 00:35:06,040 OF LINING THE INSIDE OF THE 1013 00:35:06,040 --> 00:35:07,040 VESSEL AND THEN YOU'VE GOT 1014 00:35:07,040 --> 00:35:10,840 THICKER WALLS OF SMOOTH MUSCLE 1015 00:35:10,840 --> 00:35:12,200 CELLS AROUND ARTERIES VERSUS 1016 00:35:12,200 --> 00:35:14,160 VEINS, OF COURSE, AND THEN THE 1017 00:35:14,160 --> 00:35:15,360 SMALLEST OF THE CAPILLARIES, 1018 00:35:15,360 --> 00:35:17,240 WHICH AT BEST HAVE SORT OF 1019 00:35:17,240 --> 00:35:20,920 PARASITES AROUND THE ENDOTHELIAL 1020 00:35:20,920 --> 00:35:21,480 CELLS. 1021 00:35:21,480 --> 00:35:23,680 SO THE APPROACH WE'RE TAKING 1022 00:35:23,680 --> 00:35:25,920 HERE IS ASSEMBLING DATA FROM 1023 00:35:25,920 --> 00:35:27,720 INDIVIDUAL PUBLICATIONS THAT 1024 00:35:27,720 --> 00:35:28,560 ENCOMPASS ALL OF THE TISSUES 1025 00:35:28,560 --> 00:35:31,920 THAT YOU CAN SEE HERE, WHERE -- 1026 00:35:31,920 --> 00:35:33,360 OR IN COLLABORATION WITH OTHER 1027 00:35:33,360 --> 00:35:34,760 GROUPS OR INDEPENDENT GROUPS 1028 00:35:34,760 --> 00:35:37,160 HAVE STUDIED DIFFERENT TISSUES 1029 00:35:37,160 --> 00:35:43,320 IN DEPTH, AND THEN ALSO SORT OF 1030 00:35:43,320 --> 00:35:48,800 LARGE CROSS -- ALSO RECENT BRAIN 1031 00:35:48,800 --> 00:35:50,440 PUBLICATION AND WHAT THEY DID 1032 00:35:50,440 --> 00:35:52,440 WAS ASSEMBLE THIS INTO OVER A 1033 00:35:52,440 --> 00:35:54,720 MILLION CELLS AND THEN PROCESSED 1034 00:35:54,720 --> 00:35:59,320 THE DATA IN A UNIFORM WAY TO 1035 00:35:59,320 --> 00:36:02,520 ACCOUNT FOR DONOR VARIATION, 1036 00:36:02,520 --> 00:36:03,360 DIFFERENT NOISE SUBTRACTION 1037 00:36:03,360 --> 00:36:04,680 APPROACHES AND SO ON, IN ORDER 1038 00:36:04,680 --> 00:36:08,560 TO END UP WITH ABOUT 900,000 1039 00:36:08,560 --> 00:36:10,960 CELLS AFTER QUALITY CONTROL, AND 1040 00:36:10,960 --> 00:36:14,720 SHE THEN COMPUTATIONALLY, USING 1041 00:36:14,720 --> 00:36:21,680 CELL 1042 00:36:21,680 --> 00:36:28,120 CELLTYPIST, PREDICTED ACROSS 1043 00:36:28,120 --> 00:36:29,760 THIS DATASET AND SEG MEANTED OUT 1044 00:36:29,760 --> 00:36:30,680 THE VASCULAR CELLS THAT YOU CAN 1045 00:36:30,680 --> 00:36:34,400 SEE AT THE TOP HERE, 1046 00:36:34,400 --> 00:36:35,920 ENDOTHELIAL, ENDO, MURAL, 1047 00:36:35,920 --> 00:36:37,680 DIFFERENT SMOOTH MUSCLE TYPES 1048 00:36:37,680 --> 00:36:39,920 AND SO ON AND EXCLUDED THE 1049 00:36:39,920 --> 00:36:41,960 EPITHELIAL, ET CETERA, CELLS. 1050 00:36:41,960 --> 00:36:45,360 SO WHAT WE'RE LEFT WITH, THEN, 1051 00:36:45,360 --> 00:36:48,160 IS 120,000 CELLS. 1052 00:36:48,160 --> 00:36:49,360 OR NUCLEI. 1053 00:36:49,360 --> 00:36:51,480 AND THESE BELONG TO 17 1054 00:36:51,480 --> 00:36:53,600 ENDOTHELIAL CELL SUBTYPES, EIGHT 1055 00:36:53,600 --> 00:36:55,240 MURAL CELL SUBTYPES, SO SMOOTH 1056 00:36:55,240 --> 00:36:57,120 MUSCLE AND PARASITES SURROUNDING 1057 00:36:57,120 --> 00:36:59,000 THE PACKAGING AROUND THE 1058 00:36:59,000 --> 00:37:00,440 ENDOTHELIAL CELLS, AND THEN UP 1059 00:37:00,440 --> 00:37:02,720 HERE, YOU CAN SEE LYMPHATIC 1060 00:37:02,720 --> 00:37:05,080 ENDOTHELIAL CELLS AND DOWN HERE 1061 00:37:05,080 --> 00:37:11,080 A SORT OF SPECIAL SUBSET THAT WE 1062 00:37:11,080 --> 00:37:13,480 ANNOTATED AS LITTORAL CELLS. 1063 00:37:13,480 --> 00:37:14,720 THIS IS AN INTERESTING SPECIAL 1064 00:37:14,720 --> 00:37:18,320 TIED OF ENDOTHELIAL CELL WE SEE 1065 00:37:18,320 --> 00:37:20,080 HERE FOR THE FIRST TIME IN HUMAN 1066 00:37:20,080 --> 00:37:21,160 TISSUES AT SINGLE CELL 1067 00:37:21,160 --> 00:37:23,800 RESOLUTION THAT ARE LINING THE 1068 00:37:23,800 --> 00:37:27,280 VENOUS SINUSES AT THE RED PULP. 1069 00:37:27,280 --> 00:37:29,120 FOR THESE CELLS AS FOR ALL OF 1070 00:37:29,120 --> 00:37:32,200 THE SINGLE CELL DATASETS, THE 1071 00:37:32,200 --> 00:37:33,720 COOL AND VERY POWERFUL THING IS 1072 00:37:33,720 --> 00:37:36,080 THAT YOU'RE ABLE TO DEFINE 1073 00:37:36,080 --> 00:37:37,160 ESSENTIALLY THE GENES THAT ARE 1074 00:37:37,160 --> 00:37:39,920 ACTIVE IN EACH CELL AND NUCLEUS. 1075 00:37:39,920 --> 00:37:42,520 SO YOU'RE ABLE TO PREDICT THE 1076 00:37:42,520 --> 00:37:46,560 ACTIVE SET OF PROTEINS THAT MAKE 1077 00:37:46,560 --> 00:37:48,200 UP THE CELL AND DEFINE THE 1078 00:37:48,200 --> 00:37:50,320 MOLECULAR MARKERS. 1079 00:37:50,320 --> 00:37:53,440 SO FOR THESE SPECIAL CELLS IN 1080 00:37:53,440 --> 00:37:59,640 THE SPLEEN, WE CAN -- SPECIAL 1081 00:37:59,640 --> 00:38:07,720 ENDOTHELIAL CELLS, THEY HAVE -- 1082 00:38:07,720 --> 00:38:08,920 PARASITES, SMOOTH MUSCLE CELLS 1083 00:38:08,920 --> 00:38:10,680 AND SO ON IN THE OTHER VESSELS, 1084 00:38:10,680 --> 00:38:18,720 THE OTHER CELLS. 1085 00:38:18,720 --> 00:38:21,960 THEY HAVE CHEMOKINE RECEPTOR 1086 00:38:21,960 --> 00:38:30,200 UNIQUE PROFILE, APOC1 AND SO ON. 1087 00:38:30,200 --> 00:38:35,080 THE POINT I'M TRYING TO RATE ISS 1088 00:38:35,080 --> 00:38:39,000 THE CELL-SPECIFIC MOLECULES THAT 1089 00:38:39,000 --> 00:38:40,960 CONSTITUTE THAT CELL TYPE OR 1090 00:38:40,960 --> 00:38:42,720 CELL STATE OR CELL POPULATION. 1091 00:38:42,720 --> 00:38:44,680 SO IT ALLOWS YOU TO BASICALLY 1092 00:38:44,680 --> 00:38:46,480 INTERPRET THE CHARACTERISTICS OR 1093 00:38:46,480 --> 00:38:47,520 FUNCTIONAL FEATURES OF THE CELL 1094 00:38:47,520 --> 00:38:57,160 POPULATION. 1095 00:38:57,160 --> 00:38:58,840 IN -- MOVING ON TO OTHER 1096 00:38:58,840 --> 00:39:01,360 ENDOTHELIAL CELLS, THAT WAS A 1097 00:39:01,360 --> 00:39:03,320 DESCRIPTION OF THIS CLUSTER THAT 1098 00:39:03,320 --> 00:39:05,720 YOU COULD SEE WAS KIND OF AN 1099 00:39:05,720 --> 00:39:10,120 OUTLIER VERSUS THE OTHER BLOOD 1100 00:39:10,120 --> 00:39:11,960 VESSEL ENDOTHELIAL CELLS KIND OF 1101 00:39:11,960 --> 00:39:13,640 IN TERMS OF HAVING A VERY 1102 00:39:13,640 --> 00:39:15,680 DISTINCT MOLECULAR FINGERPRINT 1103 00:39:15,680 --> 00:39:17,120 BECAUSE OF THE SPECIAL ROLE OF 1104 00:39:17,120 --> 00:39:18,200 THESE CELLS IN THE SPLEEN, WE 1105 00:39:18,200 --> 00:39:19,840 CAN SURVEY THE OTHER ENDOTHELIAL 1106 00:39:19,840 --> 00:39:23,720 CELL TYPES AND IN THE REST OFE 1107 00:39:23,720 --> 00:39:25,240 TISSUES IN THE HUMAN BODY THAT I 1108 00:39:25,240 --> 00:39:27,960 SHOWED YOU AND DEFINE THESE 17 1109 00:39:27,960 --> 00:39:29,640 SUBSETS THAT I MENTIONED. 1110 00:39:29,640 --> 00:39:31,960 THE EXCITE THING IS WHEN YOU 1111 00:39:31,960 --> 00:39:34,760 INTEGRATE ALL OF THAT DATA, 1112 00:39:34,760 --> 00:39:38,080 MEANING YOU OR SORT OF START 1113 00:39:38,080 --> 00:39:40,200 PULLING OUT SORT OF SPECIFIC 1114 00:39:40,200 --> 00:39:40,960 SUBSETS THAT HAVEN'T BEEN 1115 00:39:40,960 --> 00:39:44,800 NOTICED BEFORE IN TERMS OF WHEN 1116 00:39:44,800 --> 00:39:46,080 EACH OF THE DATASETS IS 1117 00:39:46,080 --> 00:39:48,720 CONSIDERED INDIVIDUALLY, SO THE 1118 00:39:48,720 --> 00:39:50,920 SUM OF THE PART IS GREATER THAN 1119 00:39:50,920 --> 00:39:53,240 THE WHOLE FROM A DATA MINING, 1120 00:39:53,240 --> 00:39:54,280 DATA ANALYSIS POINT OF VIEW. 1121 00:39:54,280 --> 00:39:57,480 HERE WHAT YOU CAN SEE IS THAT 1122 00:39:57,480 --> 00:40:01,640 THERE ARE VEINS AND VENULAR 1123 00:40:01,640 --> 00:40:03,400 CELLS ACROSS THE TOP HERE IN 1124 00:40:03,400 --> 00:40:08,200 THIS SORT OF BLUE SHADES, 1125 00:40:08,200 --> 00:40:10,080 ARTERIES, AND ARTERIAL CELLS IN 1126 00:40:10,080 --> 00:40:11,760 SORT OF PINKISH SHADES ON THE 1127 00:40:11,760 --> 00:40:13,160 RIGHT-HAND SIDE, AND THEN ALL 1128 00:40:13,160 --> 00:40:15,040 THE CAPILLARIES IN THE DIFFERENT 1129 00:40:15,040 --> 00:40:16,880 SHADES ALONG THE LEFT-HAND SIDE 1130 00:40:16,880 --> 00:40:18,720 HERE, AND WITHIN THESE 17 1131 00:40:18,720 --> 00:40:19,880 DIFFERENT ENDOTHELIAL CELL 1132 00:40:19,880 --> 00:40:21,640 STATES. 1133 00:40:21,640 --> 00:40:23,360 AND KIND OF SORT OF FITTINGLY 1134 00:40:23,360 --> 00:40:26,440 ACROSS THE CENTER OF THIS 1135 00:40:26,440 --> 00:40:27,120 TWO-DIMENSIONAL PROJECTION OF 1136 00:40:27,120 --> 00:40:29,520 CELL TYPES AND CELL STATES ARE 1137 00:40:29,520 --> 00:40:30,520 ENDOTHELIAL CELLS THAT ARE 1138 00:40:30,520 --> 00:40:34,440 SHARED ACROSS ALL ORGANS, THAT 1139 00:40:34,440 --> 00:40:36,840 INCLUDES ACTIVATED VENOUS 1140 00:40:36,840 --> 00:40:41,920 ENDOTHELIAL CELL TYPE, VENULAR 1141 00:40:41,920 --> 00:40:46,440 AND VENOUS ENDOTHELIAL CELLS AS 1142 00:40:46,440 --> 00:40:54,960 WELL AS -- KIND OF SPRINKLED 1143 00:40:54,960 --> 00:40:56,480 AROUND THE EDGES AND THESE 1144 00:40:56,480 --> 00:40:58,560 BELONG TO THE SORT OF CAPILLARY 1145 00:40:58,560 --> 00:41:00,960 CELL TYPES SPECIFIC TO MUSCLE 1146 00:41:00,960 --> 00:41:05,800 CELL TYPES, CARDIAC AND -- THIS 1147 00:41:05,800 --> 00:41:08,160 IS INDICATING CAPILLARIES THAT 1148 00:41:08,160 --> 00:41:12,840 ARE TAKEN FROM BETWEEN THE RIBS 1149 00:41:12,840 --> 00:41:16,640 BASICALLY, FAT CAPE CAPILLARN 1150 00:41:16,640 --> 00:41:19,480 FAT TISSUE, THEY HAVE SPECIFIC 1151 00:41:19,480 --> 00:41:20,640 SORT OF CHARACTERISTICS THAT ARE 1152 00:41:20,640 --> 00:41:24,640 DIFFERENT, AND THEN WE'VE GOT 1153 00:41:24,640 --> 00:41:27,880 AORTIC ENDOTHELIAL CELLS, END 1154 00:41:27,880 --> 00:41:34,520 CARD YAL ENDOTHELIAL CELLS, THAT 1155 00:41:34,520 --> 00:41:36,120 HAVE CHARACTERISTICS THAT ARE 1156 00:41:36,120 --> 00:41:42,680 DISTINCT FROM THE SORT OF SHARED 1157 00:41:42,680 --> 00:41:45,600 CANONICAL ARTERIOLE -- 1158 00:41:45,600 --> 00:41:47,840 ENDOTHELIAL AND CAPE LARRY CELL 1159 00:41:47,840 --> 00:41:49,920 STATES, SO THERE'S A CORE OF 1160 00:41:49,920 --> 00:41:51,120 ENDOTHELIAL CELL TYPES THAT ARE 1161 00:41:51,120 --> 00:41:52,600 SHARED ACROSS TISSUES BUT THEN 1162 00:41:52,600 --> 00:41:55,760 THERE ARE ALSO TISSUE-SPECIFIC 1163 00:41:55,760 --> 00:41:59,920 SORT OF SPECIALIZED CELL STATES 1164 00:41:59,920 --> 00:42:02,040 THAT WE CAN DEFINE IN THAT 1165 00:42:02,040 --> 00:42:04,880 UNBIASED GENOMIC APPROACH. 1166 00:42:04,880 --> 00:42:11,200 IN TERMS OF ARTERIAL CELL TYPES, 1167 00:42:11,200 --> 00:42:12,360 BASICALLY, WHAT WAS INTERESTING 1168 00:42:12,360 --> 00:42:15,960 IS THAT THERE ARE TWO MAIN KIND 1169 00:42:15,960 --> 00:42:18,480 OF CANONICAL ARTERIAL CELL TYPES 1170 00:42:18,480 --> 00:42:20,200 THAT I SHOWED YOU HERE THAT ARE 1171 00:42:20,200 --> 00:42:24,440 SHARED ACROSS ALL ORGANS THAT 1172 00:42:24,440 --> 00:42:29,160 ARE ARTERIAL AND ARTERIOLAR. 1173 00:42:29,160 --> 00:42:32,800 BASICALLY THE SORT OF MOLECULAR 1174 00:42:32,800 --> 00:42:34,440 FINGERPRINT IS DIFFERENT BETWEEN 1175 00:42:34,440 --> 00:42:39,800 THE TWO, WHERE THE 1176 00:42:39,800 --> 00:42:43,840 SULF1 POSITIVE ARTERIAL CELLS 1177 00:42:43,840 --> 00:42:45,720 ARE KIND OF ENRICHED IN THE 1178 00:42:45,720 --> 00:42:47,960 ARTERIES VERSUS THE ARTERIOLES, 1179 00:42:47,960 --> 00:42:49,200 THE SMALLER VESSELS. 1180 00:42:49,200 --> 00:42:51,560 AND IT'S NOT THAT -- SO THIS IS 1181 00:42:51,560 --> 00:42:54,480 SHOWING THE PREDICTION FROM THE 1182 00:42:54,480 --> 00:43:00,000 GENOMICS VALIDATED IN MICROSCOPY 1183 00:43:00,000 --> 00:43:09,120 STAINING OF THE SULF1, SEMA3 -- 1184 00:43:09,120 --> 00:43:12,080 IN THE GUT IN THIS CASE, AND 1185 00:43:12,080 --> 00:43:14,440 WHAT WE CAN SEE HERE IS THAT THE 1186 00:43:14,440 --> 00:43:17,800 BIGGER OF THE ARTERY IS, THE R 1187 00:43:17,800 --> 00:43:19,520 FRACTION OF THIS ENDOTHELIAL 1188 00:43:19,520 --> 00:43:20,760 CELL POPULATION THERE IS, AND WE 1189 00:43:20,760 --> 00:43:25,760 THINK THIS IS BECAUSE BASICALLY 1190 00:43:25,760 --> 00:43:29,960 THIS AR HAS MORE EXTRACELLULAR 1191 00:43:29,960 --> 00:43:31,160 MATRIX COMPONENTS, MORE 1192 00:43:31,160 --> 00:43:34,640 MOLECULES THAT ARE LINKED TO 1193 00:43:34,640 --> 00:43:35,960 ESSENTIALLY STIFFNESS BUT ALSO 1194 00:43:35,960 --> 00:43:40,480 REGULATION OF SMOOTH MUSCLE, AND 1195 00:43:40,480 --> 00:43:42,440 THE ARTERIOLAR ENDOTHELIAL CELLS 1196 00:43:42,440 --> 00:43:44,200 HAVE MORE MOLECULES ASSOCIATED 1197 00:43:44,200 --> 00:43:48,720 WITH REGULATION OF 1198 00:43:48,720 --> 00:43:49,320 ANGIOGENESIS -- DEVELOPMENT AND 1199 00:43:49,320 --> 00:43:49,840 SO ON. 1200 00:43:49,840 --> 00:43:51,440 SO THIS KIND OF SHOWS YOU THE 1201 00:43:51,440 --> 00:43:54,640 SORT OF PARADIGM FOR HOW WE CAN 1202 00:43:54,640 --> 00:43:57,160 BASICALLY MINE THE DATA FROM THE 1203 00:43:57,160 --> 00:43:57,920 GENOMICS POINT OF VIEW, 1204 00:43:57,920 --> 00:43:59,600 INTERPRET IT, AND THEN GO INTO 1205 00:43:59,600 --> 00:44:04,040 THE TISSUE SECTION, STAIN AND 1206 00:44:04,040 --> 00:44:08,240 ANALYZE MY MICROSCOPY AND STAT 1207 00:44:08,240 --> 00:44:09,400 UNDERSTANDING HOW THESE BUILDING 1208 00:44:09,400 --> 00:44:11,040 BLOCKS ACTUALLY MAKE VESSELS OF 1209 00:44:11,040 --> 00:44:12,000 DIFFERENT SIZES. 1210 00:44:12,000 --> 00:44:16,160 AND OVER HERE IS JUST AN 1211 00:44:16,160 --> 00:44:20,200 ILLUSTRATION OF A SPECIFIC -- 1212 00:44:20,200 --> 00:44:21,120 TISSUE-SPECIFIC, ORGAN-SPECIFIC 1213 00:44:21,120 --> 00:44:22,160 ENDOTHELIAL POPULATIONS 1214 00:44:22,160 --> 00:44:24,400 INCLUDING THE AORTIC ENDOTHELIAL 1215 00:44:24,400 --> 00:44:28,560 CELLS AND PULMONARY -- THAT HAVE 1216 00:44:28,560 --> 00:44:29,160 THESE SPECIFIC MOLECULAR 1217 00:44:29,160 --> 00:44:29,960 CHARACTERISTICS THAT YOU CAN SEE 1218 00:44:29,960 --> 00:44:33,000 ALONG THE BOTTOM. 1219 00:44:33,000 --> 00:44:34,520 I WON'T GO INTO TOO MUCH DETAIL 1220 00:44:34,520 --> 00:44:36,400 HERE. 1221 00:44:36,400 --> 00:44:38,920 THEN SORT OF MOVING ON TO THE 1222 00:44:38,920 --> 00:44:40,240 CAPILLARIES, WHICH, OF COURSE, 1223 00:44:40,240 --> 00:44:41,640 AREN'T SURROUNDED BY SMOOTH 1224 00:44:41,640 --> 00:44:44,160 MUSCLE BUT INSTEAD BY PARASITES, 1225 00:44:44,160 --> 00:44:46,160 WHAT WE CAN -- WE CAN 1226 00:44:46,160 --> 00:44:49,200 DISTINGUISH, AGAIN, THE 1227 00:44:49,200 --> 00:44:51,600 FINGERPRINT OF THE CAPILLARIES 1228 00:44:51,600 --> 00:44:55,240 THAT HAVE -- THAT ARE CONTINUOUS 1229 00:44:55,240 --> 00:44:57,040 VERSUS FENESTRATED VERSUS SIGN 1230 00:44:57,040 --> 00:45:05,760 SOY DAL. 1231 00:45:05,760 --> 00:45:06,240 SINUSOIDAL. 1232 00:45:06,240 --> 00:45:07,560 THIS IS SORT OF, AGAIN, SHOWING 1233 00:45:07,560 --> 00:45:10,040 THE CELL POPULATIONS ALONG THE 1234 00:45:10,040 --> 00:45:12,800 TOP, AND THEN YOU CAN SEE THESE 1235 00:45:12,800 --> 00:45:19,240 CELL TYPE-SPECIFIC FINGERPRINTS 1236 00:45:19,240 --> 00:45:21,360 BASICALLY, FOR INSTANCE, FOR THE 1237 00:45:21,360 --> 00:45:28,600 LUNG ENDOTHELIAL CELLS, RECEPTOR 1238 00:45:28,600 --> 00:45:30,080 EXPRESSION IS HIGH AS ONE 1239 00:45:30,080 --> 00:45:33,160 EXAMPLE COMPARED TO ALL THE 1240 00:45:33,160 --> 00:45:43,480 OTHER CAPILLARIES. 1241 00:45:45,200 --> 00:45:47,000 LYVE1 IS MORE -- THIS IS AN 1242 00:45:47,000 --> 00:45:48,280 ILLUSTRATION OF HOW WE CAN PULL 1243 00:45:48,280 --> 00:45:51,720 OUT THE DIFFERENT PERSONALITIES 1244 00:45:51,720 --> 00:45:53,800 OF THESE TISSUE-SPECIFIC CELL 1245 00:45:53,800 --> 00:45:54,120 TYPES. 1246 00:45:54,120 --> 00:45:55,760 YOU CAN SAY IT'S ALL VERY WELL 1247 00:45:55,760 --> 00:45:56,960 AND GOOD TO UNDERSTAND THE 1248 00:45:56,960 --> 00:46:00,400 DIFFERENT SUBSETS IN DIFFERENT 1249 00:46:00,400 --> 00:46:02,160 TISSUES AND WHAT ARE SHARED IN 1250 00:46:02,160 --> 00:46:02,800 TISSUE-SPECIFIC CHARACTERISTICS 1251 00:46:02,800 --> 00:46:04,760 BUT HOW DOES THIS HELP US 1252 00:46:04,760 --> 00:46:05,800 UNDERSTAND DISEASE? 1253 00:46:05,800 --> 00:46:08,360 ONE WAY OF KIND OF LINKING THIS 1254 00:46:08,360 --> 00:46:11,160 HUMAN CELL TYPES WITH HUMAN 1255 00:46:11,160 --> 00:46:12,760 DISEASE GENETICS IS BASICALLY 1256 00:46:12,760 --> 00:46:17,120 MAPPING ON TO -- MAPPING GWAS 1257 00:46:17,120 --> 00:46:21,280 ASSOCIATIONS ON TO THE VESSELS 1258 00:46:21,280 --> 00:46:22,360 THAT ARE SPECIFIC FOR THE 1259 00:46:22,360 --> 00:46:25,800 DISEASE, SO FOR INSTANCE, FOR 1260 00:46:25,800 --> 00:46:29,400 THE AEROCYTES, SO THE LUNG 1261 00:46:29,400 --> 00:46:31,280 CAPILLARY ENDOTHELIAL CELLS THAT 1262 00:46:31,280 --> 00:46:39,040 ARE ASSOCIATED WITH GAS 1263 00:46:39,040 --> 00:46:45,520 EXCHANGE, THE -- ON 1RL1 IS 1264 00:46:45,520 --> 00:46:47,240 SPECIFICALLY EXPRESSED IN THAT 1265 00:46:47,240 --> 00:46:49,520 ENDOTHELIAL CELL TYPE SO THIS IS 1266 00:46:49,520 --> 00:46:51,120 A WAY THAT WE CAN START TO ALSO 1267 00:46:51,120 --> 00:46:53,960 UNDERSTAND THE ROLE THAT 1268 00:46:53,960 --> 00:46:55,520 VARIATIONS IN GENES MAY PLAY IN 1269 00:46:55,520 --> 00:47:00,760 TERMS OF DISEASE ASSOCIATION. 1270 00:47:00,760 --> 00:47:01,760 THIS IS SORT OF OBVIOUSLY 1271 00:47:01,760 --> 00:47:05,520 SHOWING HOW THAT SUBUNIT OF THE 1272 00:47:05,520 --> 00:47:09,320 IL-33 RECEPTOR MAY PLAY A ROLE 1273 00:47:09,320 --> 00:47:13,160 IN THE ASSOCIATION OF ASTHMA 1274 00:47:13,160 --> 00:47:14,480 THROUGH CHANGES IN ITS AFFINITY 1275 00:47:14,480 --> 00:47:23,600 OR SIGNALING WITH THE CYTOKINE. 1276 00:47:23,600 --> 00:47:25,520 A NEXT STEP IS ALSO HOW THE 1277 00:47:25,520 --> 00:47:27,520 CELLS ARE INTERACTING WITH THE 1278 00:47:27,520 --> 00:47:28,560 TISSUE, AND THIS IS COMING BACK 1279 00:47:28,560 --> 00:47:30,280 TO INTEGRATING THE TISSUE 1280 00:47:30,280 --> 00:47:32,920 ARCHITECTURE FROM SPATIAL 1281 00:47:32,920 --> 00:47:33,680 GENOMICS DATA THAT I MENTIONED 1282 00:47:33,680 --> 00:47:34,320 AT THE BEGINNING OF THE TALK 1283 00:47:34,320 --> 00:47:35,800 WITH ALL OF THIS DATA THAT I'VE 1284 00:47:35,800 --> 00:47:37,680 BEEN DESCRIBING SO FAR THAT'S 1285 00:47:37,680 --> 00:47:42,080 BASICALLY SUSPENSION SERUM CLEAR 1286 00:47:42,080 --> 00:47:42,600 ANALYSIS. 1287 00:47:42,600 --> 00:47:51,600 I'M GOING TO JUMP ON TO THE 1288 00:47:51,600 --> 00:47:52,720 LYMPHATIC ENDOTHELIAL CELLS THAT 1289 00:47:52,720 --> 00:47:56,200 MAY BE OF MOST RELEVANCE FOR 1290 00:47:56,200 --> 00:47:57,800 THIS AUDIENCE, AND WHAT WE DID 1291 00:47:57,800 --> 00:47:59,040 HERE WAS BASICALLY INTEGRATE OUR 1292 00:47:59,040 --> 00:48:00,400 DATA FROM ACROSS THE BODY, AND 1293 00:48:00,400 --> 00:48:03,120 THAT INCLUDES INGUINAL LYMPH 1294 00:48:03,120 --> 00:48:06,480 NODES, MESENTERIC LYMPH NODES AS 1295 00:48:06,480 --> 00:48:08,440 WELL AS LYMPHOID TISSUE FROM 1296 00:48:08,440 --> 00:48:10,080 OTHER ORGANS. 1297 00:48:10,080 --> 00:48:13,320 THIS ENTIRE LYMPH NODE IS IN 1298 00:48:13,320 --> 00:48:18,400 BROWN, INGUINAL LYMPH NODE IS IN 1299 00:48:18,400 --> 00:48:19,600 PURPLE AND THEN DETERMINE 1300 00:48:19,600 --> 00:48:22,680 DIFFERENT SUBSETS OF THEEL YAL 1301 00:48:22,680 --> 00:48:24,640 CELLS IN OUR LARGE INTEGRATED 1302 00:48:24,640 --> 00:48:25,640 DATASET. 1303 00:48:25,640 --> 00:48:28,800 WHAT WAS VERY HELPFUL WAS THIS 1304 00:48:28,800 --> 00:48:31,240 PUBLICATION FROM ABE ET AL. 1305 00:48:31,240 --> 00:48:33,560 WHERE THEY STUDIED LYMPHOMA IN 1306 00:48:33,560 --> 00:48:34,560 LUNG DISEASE AND LUNG DISEASE 1307 00:48:34,560 --> 00:48:35,080 BIOPSIES. 1308 00:48:35,080 --> 00:48:36,840 OUR DATA IS A LOT FROM ORGAN 1309 00:48:36,840 --> 00:48:38,240 DONOR TISSUES WHERE THERE'S 1310 00:48:38,240 --> 00:48:39,840 LARGE CHUNKS OF TISSUE THAT WE 1311 00:48:39,840 --> 00:48:40,480 CAN ANALYZE. 1312 00:48:40,480 --> 00:48:42,120 WHAT THIS ALLOWS US TO DO IS TO 1313 00:48:42,120 --> 00:48:44,480 FIND AT THE MOLECULAR LEVEL THE 1314 00:48:44,480 --> 00:48:48,720 DIFFERENT SUBSETS OF LYMPHATIC 1315 00:48:48,720 --> 00:48:51,800 ENDOTHELIAL CELLS IN LYMPH 1316 00:48:51,800 --> 00:48:52,520 NODES. 1317 00:48:52,520 --> 00:48:54,160 YOU CAN SEE SPECIFICALLY HERE IN 1318 00:48:54,160 --> 00:48:55,960 DIFFERENT COLORS THE DIFFERENT 1319 00:48:55,960 --> 00:49:00,880 ENDOTHELIAL CELLS KIND OF LINING 1320 00:49:00,880 --> 00:49:09,120 THE -- 'FESS ELSE, -- VR 1321 00:49:09,120 --> 00:49:13,080 MEDULLARY ENDOTHELIAL CELLS 1322 00:49:13,080 --> 00:49:14,400 BRIDGE, SINUS ENDOTHELIAL CELLS 1323 00:49:14,400 --> 00:49:14,960 AND SO ON. 1324 00:49:14,960 --> 00:49:16,480 WHAT WE'RE ABLE TO DO HERE IS 1325 00:49:16,480 --> 00:49:17,880 THEN DIG INTO THE MOLECULAR 1326 00:49:17,880 --> 00:49:19,120 FINGERPRINT OF THESE DIFFERENT 1327 00:49:19,120 --> 00:49:20,920 CELL POPULATIONS AND UNDERSTAND 1328 00:49:20,920 --> 00:49:26,720 IN DETAIL SORT OF WHAT 1329 00:49:26,720 --> 00:49:27,360 CONSTITUTES THE EXPRESSION 1330 00:49:27,360 --> 00:49:29,000 PATTERN OF THESE DIFFERENT 1331 00:49:29,000 --> 00:49:33,640 ENDOTHELIAL CELL POPULATIONS. 1332 00:49:33,640 --> 00:49:35,040 THIS IS SIMPLY SCRATCHING THE 1333 00:49:35,040 --> 00:49:37,240 SURFACE OF THIS DATA, BUT WHAT 1334 00:49:37,240 --> 00:49:41,240 WE SEE, FOR INSTANCE, IS THAT 1335 00:49:41,240 --> 00:49:45,480 LYVE1 IS EXPRESSED HIGHLY IN THE 1336 00:49:45,480 --> 00:49:46,680 MEDULLA, THE LYMPHATIC 1337 00:49:46,680 --> 00:49:49,280 ENDOTHELIAL CELLS BUT NOT IN THE 1338 00:49:49,280 --> 00:49:55,520 FLOOR, CEILING OR VALVULAR 1339 00:49:55,520 --> 00:49:56,120 ENDOTHELIAL CELLS. 1340 00:49:56,120 --> 00:50:02,480 THE MEDULLAR IS EXPRESSED IN THE 1341 00:50:02,480 --> 00:50:05,360 VALVE AND CORTEX BEING LYMPHATIC 1342 00:50:05,360 --> 00:50:10,600 ENDOTHELIAL CELLS, SO THERE'S A 1343 00:50:10,600 --> 00:50:13,160 LOT OF BEAUTIFUL MOLECULAR 1344 00:50:13,160 --> 00:50:15,520 DETAIL THAT WE CAN STUDY IN MUCH 1345 00:50:15,520 --> 00:50:21,760 MORE DETAIL FROM THIS CELL DATA. 1346 00:50:21,760 --> 00:50:23,120 SO I'M JUST GOING TO WRAP UP 1347 00:50:23,120 --> 00:50:24,320 THERE, AND I HOPE THAT THIS HAS 1348 00:50:24,320 --> 00:50:27,080 GIVEN YOU A KIND OF IMPRESSION 1349 00:50:27,080 --> 00:50:36,960 OF WHAT WE CAN LEARN FROM BLOOD 1350 00:50:36,960 --> 00:50:39,440 AND LYMPHATIC FROM THIS HIGH 1351 00:50:39,440 --> 00:50:40,360 RESOLUTION GENOMICS DATA, THAT 1352 00:50:40,360 --> 00:50:42,640 WE CAN UNDERSTAND THE ORGAN AND 1353 00:50:42,640 --> 00:50:43,640 TISSUE-SPECIFIC FUNCTIONAL 1354 00:50:43,640 --> 00:50:44,760 ADAPTATIONS OF THE DIFFERENT 1355 00:50:44,760 --> 00:50:47,400 CELL TYPES, AND MAP DISEASE 1356 00:50:47,400 --> 00:50:49,040 ASSOCIATIONS AND ALSO DRUG 1357 00:50:49,040 --> 00:50:50,240 TARGETS ON TO THESE CELL TYPES 1358 00:50:50,240 --> 00:50:51,880 AND START TO UNDERSTAND HOW 1359 00:50:51,880 --> 00:50:58,000 DRUGS MAY BE AFFECT BEING THE AE 1360 00:50:58,000 --> 00:50:58,360 VASCULATURE. 1361 00:50:58,360 --> 00:51:02,640 I MENTIONED BRIEFLY KIND OF 1362 00:51:02,640 --> 00:51:03,520 DEFINING VASCULAR CELL TYPES 1363 00:51:03,520 --> 00:51:08,240 FROM THERE DATA, END CARD YAL 1364 00:51:08,240 --> 00:51:13,880 CELLS, SPLENIC SINUSOIDAL 1365 00:51:13,880 --> 00:51:16,520 CAPILLARY ENDOTHELIAL CELLS, 1366 00:51:16,520 --> 00:51:19,360 MULL 1367 00:51:19,360 --> 00:51:24,960 PULMONARY ARTERY PERICYTES, HOW 1368 00:51:24,960 --> 00:51:26,040 THESE BUILDING BLOCKS OF CELLS 1369 00:51:26,040 --> 00:51:27,280 INTERACT WITH EACH OTHER TO MAKE 1370 00:51:27,280 --> 00:51:28,600 THE VESSELS AND HOW THEY 1371 00:51:28,600 --> 00:51:29,880 INTERACT WITH THE OUTSIDE 1372 00:51:29,880 --> 00:51:31,840 TISSUE, WHICH YOU CAN OBVIOUSLY 1373 00:51:31,840 --> 00:51:33,560 START TO PUT THESE PIECES OF THE 1374 00:51:33,560 --> 00:51:36,640 JIGSAW PUZZLE TOGETHER USING THE 1375 00:51:36,640 --> 00:51:38,040 SPATIAL GENOMICS DATA AND 1376 00:51:38,040 --> 00:51:40,360 INTEGRATING THE SINGLE CELL 1377 00:51:40,360 --> 00:51:40,640 GENOMICS. 1378 00:51:40,640 --> 00:51:43,360 I WANT TO SAY THANK YOU TO LING 1379 00:51:43,360 --> 00:51:45,760 WHO I'VE MENTIONED WHO'S A 1380 00:51:45,760 --> 00:51:48,040 TALENTED POSTDOC IN THE GROUP. 1381 00:51:48,040 --> 00:51:52,160 SHE'S WORKED WITH ANA-MARIA 1382 00:51:52,160 --> 00:51:57,800 CUJBA AND OTHER MEMBERS OF MY 1383 00:51:57,800 --> 00:52:01,360 GROUP, MICHAELA NOSEDA. 1384 00:52:01,360 --> 00:52:02,520 I WILL FINISH THERE, SAY THANK 1385 00:52:02,520 --> 00:52:03,920 YOU AND TAKE ANY QUESTIONS NOW 1386 00:52:03,920 --> 00:52:05,320 OR IN THE Q & A SESSION. 1387 00:52:05,320 --> 00:52:06,360 THANKS. 1388 00:52:06,360 --> 00:52:09,520 >> THANK YOU SO MUCH, SARAH. 1389 00:52:09,520 --> 00:52:10,640 THAT WAS ABSOLUTELY EXCELLENT 1390 00:52:10,640 --> 00:52:11,600 AND GAVE US A LOT TO THINK 1391 00:52:11,600 --> 00:52:12,120 ABOUT. 1392 00:52:12,120 --> 00:52:13,080 WE'LL HAVE TO -- THANK YOU 1393 00:52:13,080 --> 00:52:13,280 AGAIN. 1394 00:52:13,280 --> 00:52:14,240 WE'LL HAVE TO RESERVE THE 1395 00:52:14,240 --> 00:52:16,760 QUESTIONS TO THE END OF SESSION 1396 00:52:16,760 --> 00:52:18,000 TWO, IF YOU CAN HANG AROUND. 1397 00:52:18,000 --> 00:52:19,560 IF NOT, WE'LL DO SOMETHING ELSE, 1398 00:52:19,560 --> 00:52:21,000 BUT THANK YOU, SARAH. 1399 00:52:21,000 --> 00:52:22,760 I'LL HAND IT OVER TO TIM. 1400 00:52:22,760 --> 00:52:27,440 THANK YOU VERY MUCH. 1401 00:52:27,440 --> 00:52:33,160 >> GREAT, AND GOOD MORNING, 1402 00:52:33,160 --> 00:52:33,440 EVERYONE. 1403 00:52:33,440 --> 00:52:35,280 >> I'D BETTER INTRODUCE YOU. 1404 00:52:35,280 --> 00:52:36,520 >> OH, SORRY. 1405 00:52:36,520 --> 00:52:37,960 SORRY ABOUT THAT. 1406 00:52:37,960 --> 00:52:40,120 >> IT'S MY PLEASURE TO INTRODUCE 1407 00:52:40,120 --> 00:52:42,720 OUR MODERATOR FOR THIS SESSION, 1408 00:52:42,720 --> 00:52:45,360 DR. TIM PADERA, ASSOCIATE 1409 00:52:45,360 --> 00:52:46,000 PROFESSOR AT THE MASSACHUSETTS 1410 00:52:46,000 --> 00:52:47,760 GENERAL HOSPITAL, WHERE HE 1411 00:52:47,760 --> 00:52:48,560 STUDIES LYMPHATIC FUNCTION IN 1412 00:52:48,560 --> 00:52:49,920 TUMORS AND OTHER PATHOLOGIC 1413 00:52:49,920 --> 00:52:51,120 CONDITIONS. 1414 00:52:51,120 --> 00:52:53,400 HE'S DEVELOPED MANY NOVEL TOOLS 1415 00:52:53,400 --> 00:53:01,720 AND MADE IMPORTANT PROGRESS IN 1416 00:53:01,720 --> 00:53:03,240 UNDERSTANDING TUMOR METASTASIS. 1417 00:53:03,240 --> 00:53:04,680 >> THANK YOU FOR INTRODUCING ME 1418 00:53:04,680 --> 00:53:06,240 AND THAT KIND INTRODUCTION. 1419 00:53:06,240 --> 00:53:08,280 I NOW HAVE THE HONOR OF 1420 00:53:08,280 --> 00:53:09,680 INTRODUCING OUR FIRST SPEAKER, 1421 00:53:09,680 --> 00:53:11,080 WHO'S ALSO A FRIEND AND 1422 00:53:11,080 --> 00:53:13,720 COLLEAGUE HERE IN BOSTON, 1423 00:53:13,720 --> 00:53:17,920 DR. DHRUV SINGHAL AT THE BETH 1424 00:53:17,920 --> 00:53:18,720 ISRAEL DEACONESS MEDICAL CENTER 1425 00:53:18,720 --> 00:53:20,040 OR SCHOOL. 1426 00:53:20,040 --> 00:53:21,560 DHRUV, IF YOU'RE ON IF YOU WANT 1427 00:53:21,560 --> 00:53:22,960 TO START SHARING YOUR SLIDES AND 1428 00:53:22,960 --> 00:53:24,560 WE'RE GOING TO HEAR A JOURNEY 1429 00:53:24,560 --> 00:53:27,080 FROM HIM AND HIS TITLE IS 1430 00:53:27,080 --> 00:53:29,160 PREVENTING BREAST CANCER-RELATED 1431 00:53:29,160 --> 00:53:30,600 LYMPHEDEMA, A SURGEON'S JOURNEY 1432 00:53:30,600 --> 00:53:31,600 HIGHLIGHTING THE IMPORTANCE OF 1433 00:53:31,600 --> 00:53:32,400 LYMPHATIC ANATOMY. 1434 00:53:32,400 --> 00:53:33,800 >> THANKS FOR THAT KIND 1435 00:53:33,800 --> 00:53:34,640 INTRODUCTION. 1436 00:53:34,640 --> 00:53:38,440 I'D LIKE TO THANK YOU, ZORINA, 1437 00:53:38,440 --> 00:53:40,400 SELEN, ANDREA, BABAK, FOR THE 1438 00:53:40,400 --> 00:53:41,560 HONOR OF PRESENTING IN THIS 1439 00:53:41,560 --> 00:53:43,080 FORUM. 1440 00:53:43,080 --> 00:53:45,160 PREVENTING BREAST CANCER-RELATED 1441 00:53:45,160 --> 00:53:46,960 LYMPHEDEMA, A SURGEON'S JOURNEY 1442 00:53:46,960 --> 00:53:48,320 HIGHLIGHTING THE IMPORTANCE OF 1443 00:53:48,320 --> 00:53:49,520 LYMPHATIC ANATOMY, WE'RE GOING 1444 00:53:49,520 --> 00:53:51,720 TO BE SHIFTING FROM A MICRO 1445 00:53:51,720 --> 00:53:53,360 SCALE TO THE MACRO SCALE, BUT AT 1446 00:53:53,360 --> 00:53:54,360 THE VERY END OF THIS TALK, WE'RE 1447 00:53:54,360 --> 00:53:56,440 GOING TO GO BACK A LITTLE BIT TO 1448 00:53:56,440 --> 00:53:57,600 THE MICRO SCALE. 1449 00:53:57,600 --> 00:53:59,480 DISCLOSURE, I DO RUN THE BOSTON 1450 00:53:59,480 --> 00:54:01,000 LYMPHATIC SYMPOSIUM, I DO WORK 1451 00:54:01,000 --> 00:54:03,680 VERY CLOSELY WITH INDUSTRY IN 1452 00:54:03,680 --> 00:54:04,360 THE LYMPHATIC FIELD. 1453 00:54:04,360 --> 00:54:05,600 WHILE I DON'T MAKE ANY MONEY 1454 00:54:05,600 --> 00:54:07,440 FROM THIS, THEY ARE CRITICAL TO 1455 00:54:07,440 --> 00:54:09,640 RUNNING OUR SYMPOSIUM. 1456 00:54:09,640 --> 00:54:11,840 THE OUTLINE OF MY TALK, I'M 1457 00:54:11,840 --> 00:54:13,160 GOING TO GIVE A LITTLE BIT OF 1458 00:54:13,160 --> 00:54:14,800 BACKGROUND ABOUT BREAST 1459 00:54:14,800 --> 00:54:15,480 CANCER-RELATED LYMPHEDEMA, AND 1460 00:54:15,480 --> 00:54:17,800 THEN I'M GOING TO TALK ABOUT 1461 00:54:17,800 --> 00:54:19,080 IMMEDIATE LYMPHATIC 1462 00:54:19,080 --> 00:54:19,680 RECONSTRUCTION, WHICH IS A 1463 00:54:19,680 --> 00:54:21,560 SURGICAL TECHNIQUE TO TRY TO 1464 00:54:21,560 --> 00:54:23,560 PREVENT THE DEVELOPMENT OF 1465 00:54:23,560 --> 00:54:24,320 LYMPHEDEMA, AND THEN I'LL TALK 1466 00:54:24,320 --> 00:54:27,600 TO YOU ABOUT WHAT KEEPS ME UP AT 1467 00:54:27,600 --> 00:54:28,760 NIGHT, WHICH IS LYMPHATIC 1468 00:54:28,760 --> 00:54:30,400 ANATOMY AND HOW I BELIEVE 1469 00:54:30,400 --> 00:54:31,760 LYMPHATIC ANATOMY PLAYS A 1470 00:54:31,760 --> 00:54:33,640 CRITICAL ROLE IN THE PREVENTION 1471 00:54:33,640 --> 00:54:35,960 OF THIS DISEASE. 1472 00:54:35,960 --> 00:54:37,680 SO FOR BACKGROUND, THERE ARE 1473 00:54:37,680 --> 00:54:39,200 ABOUT -- I KNOW THIS IS A MOVING 1474 00:54:39,200 --> 00:54:41,680 TARGET, BUT THERE ARE ABOUT 1475 00:54:41,680 --> 00:54:42,440 3.8 MILLION BREAST CANCER 1476 00:54:42,440 --> 00:54:44,320 SURVIVORS AND 1 IN 5 WILL GO ON 1477 00:54:44,320 --> 00:54:50,760 TO DEVELOP LYMPHEDEMA. 1478 00:54:50,760 --> 00:54:52,320 WHILE A LYMPHATIC SURGEON AND 1479 00:54:52,320 --> 00:54:53,800 COMMUNITY WE REALLY BELIEVE IN 1480 00:54:53,800 --> 00:54:57,400 OUR PROCEDURES IN LYMPH NODE 1481 00:54:57,400 --> 00:54:59,240 TRANSPLANTATION AND WHILE THERE 1482 00:54:59,240 --> 00:55:00,400 ARE GOOD OUTCOMES FROM THIS, I 1483 00:55:00,400 --> 00:55:01,760 DON'T THINK THERE'S A SINGLE 1484 00:55:01,760 --> 00:55:03,280 LYMPHATIC SURGEON THAT WALKS 1485 00:55:03,280 --> 00:55:04,920 AROUND AND CLAIM THAT THEY CAN 1486 00:55:04,920 --> 00:55:06,640 RELIABLY AND ACCURATELY 1487 00:55:06,640 --> 00:55:09,360 CONSISTENTLY CURE LYMPHEDEMA. 1488 00:55:09,360 --> 00:55:11,640 SO GIVEN THE FACT THAT WE KNOW 1489 00:55:11,640 --> 00:55:16,080 THAT LYMPHEDEMA IS A PROGRESSIVE 1490 00:55:16,080 --> 00:55:17,080 DISEASE, WE WANT TO TRY TO 1491 00:55:17,080 --> 00:55:18,640 PREVENT IT, ESPECIALLY IN 1492 00:55:18,640 --> 00:55:20,000 DEVELOPED COUNTRIES, WHERE THE 1493 00:55:20,000 --> 00:55:22,600 NUMBER ONE CAUSE OF LYMPHEDEMA 1494 00:55:22,600 --> 00:55:25,800 OCCURS AT THE TIME OF CANCER 1495 00:55:25,800 --> 00:55:27,520 TREATMENT. 1496 00:55:27,520 --> 00:55:29,440 SO I WANT TO TALK SPECIFICALLY 1497 00:55:29,440 --> 00:55:31,640 ABOUT ILR OR IMMEDIATE LYMPHATIC 1498 00:55:31,640 --> 00:55:32,320 RECONSTRUCTION. 1499 00:55:32,320 --> 00:55:33,360 WE'LL START WITH A MODERN 1500 00:55:33,360 --> 00:55:36,360 HISTORY OF THIS. 1501 00:55:36,360 --> 00:55:38,200 SO THIS CONCEPT REALLY BEGAN IN 1502 00:55:38,200 --> 00:55:42,280 2007 WHEN A BREAST SURGEON, 1503 00:55:42,280 --> 00:55:43,800 DR. KLIMBERG, CAME UP WITH 1504 00:55:43,800 --> 00:55:45,200 AXILLARY REVERSE MAPPING WHERE 1505 00:55:45,200 --> 00:55:48,240 SHE RECOGNIZED RESECTION IN 1506 00:55:48,240 --> 00:55:50,560 BREAST CANCER TREATMENT WAS THE 1507 00:55:50,560 --> 00:55:51,680 HIGHEST RISK FACTOR FOR 1508 00:55:51,680 --> 00:55:52,600 DEVELOPING LYMPHEDEMA. 1509 00:55:52,600 --> 00:55:55,080 SO SHE SAID WHY DON'T WE INJECT 1510 00:55:55,080 --> 00:56:00,200 A BLUE DYE INTO THE ARM 1511 00:56:00,200 --> 00:56:01,720 LYMPHATICS, LEAVE THE BLUE LYMPH 1512 00:56:01,720 --> 00:56:03,360 NODES BEHIND BECAUSE THEY'RE 1513 00:56:03,360 --> 00:56:04,440 PRESUMABLY DRAINING THE ARM AND 1514 00:56:04,440 --> 00:56:04,920 NOT THE BREAST. 1515 00:56:04,920 --> 00:56:07,120 BY DOING SO, THE RATES OF 1516 00:56:07,120 --> 00:56:09,760 LYMPHEDEMA DID PRELIMINARILY 1517 00:56:09,760 --> 00:56:11,480 PLUMMET DOWN TO THE SINGLE 1518 00:56:11,480 --> 00:56:11,720 DIGITS. 1519 00:56:11,720 --> 00:56:13,880 THE PROBLEM WAS THOSE BLUE LYMPH 1520 00:56:13,880 --> 00:56:14,600 NODES CROSSTALK. 1521 00:56:14,600 --> 00:56:16,360 THEY DRAIN NOT ONLY THE ARM BUT 1522 00:56:16,360 --> 00:56:16,960 THE BREAST. 1523 00:56:16,960 --> 00:56:18,760 AND FOR THAT REASON, THE 1524 00:56:18,760 --> 00:56:19,880 ONCOLOGIC SAFETY OF THIS IS 1525 00:56:19,880 --> 00:56:23,200 BEING FURTHER TESTED IN A 1526 00:56:23,200 --> 00:56:25,480 MULTICENTER TRIAL CURRENTLY 1527 00:56:25,480 --> 00:56:25,720 ONGOING. 1528 00:56:25,720 --> 00:56:30,080 BUT THE SURGEONS IN ITALY, 1529 00:56:30,080 --> 00:56:32,480 DR. BOCCARDO AND CAMPISI IN 1530 00:56:32,480 --> 00:56:34,320 2009, SAID LET'S TAKE THIS ONE 1531 00:56:34,320 --> 00:56:34,840 STEP FURTHER. 1532 00:56:34,840 --> 00:56:37,240 THEY SAID WHY DON'T YOU TAKE OUT 1533 00:56:37,240 --> 00:56:38,640 BLUE LYMPH NODES AND AS 1534 00:56:38,640 --> 00:56:39,520 LYMPHATIC SURGEONS, WE'LL LET 1535 00:56:39,520 --> 00:56:42,120 YOU FIND THE BLUE LYMPHATICS AND 1536 00:56:42,120 --> 00:56:42,960 BYPASS IT INTO A VEIN. 1537 00:56:42,960 --> 00:56:48,760 AND BY DOING SO, THEY REPORTED 1538 00:56:48,760 --> 00:56:50,400 AT FOUR-YEAR FOLLOW-UP WHICH IS 1539 00:56:50,400 --> 00:56:51,680 SIGNIFICANT FOLLOW-UP IN THIS 1540 00:56:51,680 --> 00:56:53,800 FIELD, AN INCIDENCE OF 4% OF 1541 00:56:53,800 --> 00:56:54,400 LYMPHEDEMA IN THE PATIENT 1542 00:56:54,400 --> 00:56:54,920 POPULATION. 1543 00:56:54,920 --> 00:56:57,640 NOW, THIS IS IN CONTRAST TO 1544 00:56:57,640 --> 00:56:59,400 HISTORICAL CONTROL, WHICH REALLY 1545 00:56:59,400 --> 00:57:02,960 ARE THE 26 TO 33% RANGE FOR 1546 00:57:02,960 --> 00:57:04,600 THEIR PATIENT COHORT, SO THIS IS 1547 00:57:04,600 --> 00:57:05,080 QUITE SIGNIFICANT. 1548 00:57:05,080 --> 00:57:09,720 I DO WANT TO NOTE THAT THEY TERM 1549 00:57:09,720 --> 00:57:15,360 THIS PROCEDURE IN LYMPHA, WE'VE 1550 00:57:15,360 --> 00:57:16,840 CHANGED THE NAME OVER TO 1551 00:57:16,840 --> 00:57:18,880 IMMEDIATE LYMPHATIC 1552 00:57:18,880 --> 00:57:21,240 RECONSTRUCTION. 1553 00:57:21,240 --> 00:57:21,840 DR. BOCCARDO IS IN AGREEMENT 1554 00:57:21,840 --> 00:57:24,920 WITH THE CHAIK OF THE -- THF 1555 00:57:24,920 --> 00:57:28,640 THE NAMING BUT THIS IS THE EXACT 1556 00:57:28,640 --> 00:57:30,480 SAME PROCEDURE AS LYMPHA IN THE 1557 00:57:30,480 --> 00:57:30,840 LITERATURE. 1558 00:57:30,840 --> 00:57:31,920 I WANT TO TALK ABOUT OUR 1559 00:57:31,920 --> 00:57:32,440 EXPERIENCE. 1560 00:57:32,440 --> 00:57:33,440 TO SHOW OUR EXPERIENCE, I WANT 1561 00:57:33,440 --> 00:57:35,280 TO SHOW YOU A VIDEO. 1562 00:57:35,280 --> 00:57:36,480 THE ONE IMPORTANT MODIFICATION 1563 00:57:36,480 --> 00:57:40,400 WE DID IS WE'VE REALLY 1564 00:57:40,400 --> 00:57:46,920 INTRODUCED THESE FLUOROSINE, 1565 00:57:46,920 --> 00:57:49,120 THERE ARE A VARIETY OF REASONS 1566 00:57:49,120 --> 00:57:50,240 FOR THIS IMPORTANT TO SURGICAL 1567 00:57:50,240 --> 00:57:52,160 COMMUNITY AND WE'VE CHANGED OUR 1568 00:57:52,160 --> 00:57:54,200 INJECTION SITES. 1569 00:57:54,200 --> 00:57:56,400 WE'RE INJECTING IT IN THE ARM 1570 00:57:56,400 --> 00:58:01,840 BEFORE WE BEGIN OUR PROCEDURE OF 1571 00:58:01,840 --> 00:58:04,400 THE AXILLA -- HERE'S THE ARM 1572 00:58:04,400 --> 00:58:05,800 OVER HERE, THE HEAD IS OVER 1573 00:58:05,800 --> 00:58:07,800 HERE, AND HERE ARE LEVEL ONE 1574 00:58:07,800 --> 00:58:08,280 LYMPH NODES. 1575 00:58:08,280 --> 00:58:10,680 USING A SPECIALIZED FILTER ON 1576 00:58:10,680 --> 00:58:12,280 OUR MICROSCOPE, WE CAN ACTUALLY 1577 00:58:12,280 --> 00:58:17,920 SEE THE FLUROSINE AND HERE THEY 1578 00:58:17,920 --> 00:58:18,560 ARE. 1579 00:58:18,560 --> 00:58:20,960 WE COME BACK IN AND HERE THEY 1580 00:58:20,960 --> 00:58:21,400 ARE. 1581 00:58:21,400 --> 00:58:23,400 IF YOU LOOK AT THEM, YOU CAN 1582 00:58:23,400 --> 00:58:24,760 ACTUALLY SEE ARM LYMPH IS 1583 00:58:24,760 --> 00:58:26,280 SPILLING RIGHT INTO THE DEFECT. 1584 00:58:26,280 --> 00:58:35,880 AND WE ISOLATE THESE CHANNELS, E 1585 00:58:35,880 --> 00:58:36,840 LITERALLY -- THEM INTO A VEIN. 1586 00:58:36,840 --> 00:58:39,160 THIS IS A TEMPORARY STITCH, BUT 1587 00:58:39,160 --> 00:58:40,680 IT DOES A JOB IN TERMS OF 1588 00:58:40,680 --> 00:58:41,720 POSITIONING THINGS WHERE WE NEED 1589 00:58:41,720 --> 00:58:42,920 THEM, AND THEN WE TAKE THE VEIN 1590 00:58:42,920 --> 00:58:45,480 AND WE SECURE TO THE 1591 00:58:45,480 --> 00:58:46,400 PERILYMPHATIC TISSUE. 1592 00:58:46,400 --> 00:58:48,280 WE REMOVE THE INITIAL STITCH, WE 1593 00:58:48,280 --> 00:58:50,000 LOOK UNDER THE FILTER, YOU CAN 1594 00:58:50,000 --> 00:58:52,720 NOW SEE THE DYE GOING INTO THE 1595 00:58:52,720 --> 00:58:53,560 VEIN. 1596 00:58:53,560 --> 00:58:55,760 WE REMOVE THE CLAMP, WAIT AN 1597 00:58:55,760 --> 00:58:57,960 HOUR DURING A BREAST 1598 00:58:57,960 --> 00:58:58,560 RECONSTRUCTION AT THE SAME TIME, 1599 00:58:58,560 --> 00:58:59,760 AND WE COME BACK AND WE LOOK, 1600 00:58:59,760 --> 00:59:02,160 AND NOW I CAN SEE THAT VEIN IS 1601 00:59:02,160 --> 00:59:03,240 FULL OF ARM LYMPH. 1602 00:59:03,240 --> 00:59:05,400 SO IN ESSENCE, WE'VE BYPASSED 1603 00:59:05,400 --> 00:59:08,240 THE ARM LYMPH INTO A VEIN. 1604 00:59:08,240 --> 00:59:10,640 RECENTLY, WE HAD OUR FOUR-YEAR 1605 00:59:10,640 --> 00:59:15,000 INSTITUTIONAL EXPERIENCE ON ILR 1606 00:59:15,000 --> 00:59:16,200 ACCEPTED IN JOURNAL PRS, AND 1607 00:59:16,200 --> 00:59:18,600 JUST TO GET TO THE CRUX OF IT, 1608 00:59:18,600 --> 00:59:20,320 WE WERE REPORTING ON 90 PATIENTS 1609 00:59:20,320 --> 00:59:21,680 HERE, WE ONLY INCLUDED PATIENTS 1610 00:59:21,680 --> 00:59:23,200 WHERE WE HAVE A MINIMUM OF 1611 00:59:23,200 --> 00:59:25,000 SIX-MONTH FOLLOW-UP, AND WHERE 1612 00:59:25,000 --> 00:59:29,080 WE ACTUALLY SUCCESSFULLY 1613 00:59:29,080 --> 00:59:30,720 COMPLETED AN ILR PROCEDURE. 1614 00:59:30,720 --> 00:59:31,560 I WOULD LIKE TO NOTE THE 1615 00:59:31,560 --> 00:59:35,160 MAJORITY OF THESE PATIENTS GOT 1616 00:59:35,160 --> 00:59:35,800 ADJUVANT RADIOTHERAPY, OF WHICH 1617 00:59:35,800 --> 00:59:38,280 THE MAJORITY WAS REGIONAL LYMPH 1618 00:59:38,280 --> 00:59:39,960 NODE RADIATION, AND AGAIN, 1619 00:59:39,960 --> 00:59:41,360 MEDIAN NUMBER OF LYMPH NODES 1620 00:59:41,360 --> 00:59:43,240 REMOVED HERE IS AT 14. 1621 00:59:43,240 --> 00:59:46,560 SO AGAIN, THE INCIDENCE OF 1622 00:59:46,560 --> 00:59:50,040 LYMPHEDEMA USING A SO-CALLED 1623 00:59:50,040 --> 00:59:51,800 CONTROL SHOULD BE APPROACHING 1624 00:59:51,800 --> 00:59:52,720 ABOUT THE 26% NUMBER. 1625 00:59:52,720 --> 00:59:55,640 THIS IS ALL 90 PATIENTS HERE, A 1626 00:59:55,640 --> 00:59:56,920 CLEAR CIRCLE REPRESENTS A VISIT 1627 00:59:56,920 --> 01:00:00,560 IN OUR CENTER POSTOPERATIVELY, A 1628 01:00:00,560 --> 01:00:01,960 CLEAR ONE MEANS THEY DID NOT 1629 01:00:01,960 --> 01:00:03,040 MEET THE CRITERIA FOR LYMPHEDEMA 1630 01:00:03,040 --> 01:00:05,360 AND DARK CIRCLE MEANS THEY DID. 1631 01:00:05,360 --> 01:00:08,720 SO ESSENTIALLY AVERAGE FOLLOW-UP 1632 01:00:08,720 --> 01:00:10,240 AT 17 MONTHS, WE HAVE A 1633 01:00:10,240 --> 01:00:13,640 FOLLOW-UP RATE AT 9%, AGAIN 1634 01:00:13,640 --> 01:00:14,600 AGAINST HISTORICAL CONTROLS, 1635 01:00:14,600 --> 01:00:16,880 WHICH SHOULD BE AROUND 26%. 1636 01:00:16,880 --> 01:00:18,440 SO THAT'S ILR AND THAT'S OUR 1637 01:00:18,440 --> 01:00:19,640 EXPERIENCE, AND NOW I WANT TO 1638 01:00:19,640 --> 01:00:20,920 DIVE INTO WHAT KEEPS ME UP AT 1639 01:00:20,920 --> 01:00:22,560 NIGHT. 1640 01:00:22,560 --> 01:00:25,640 SO WHEN YOU LOOK AT THE 1641 01:00:25,640 --> 01:00:27,320 INCIDENCE OF LYMPHEDEMA, WE ALL 1642 01:00:27,320 --> 01:00:33,720 KNOW WHAT THE MAIN RISK FACTORS 1643 01:00:33,720 --> 01:00:34,160 ARE. 1644 01:00:34,160 --> 01:00:36,800 EVEN IF YOU TAKE ALL THREE RISK 1645 01:00:36,800 --> 01:00:39,240 FACTORS, ONLY 1 IN 3 ABOUT OR 1646 01:00:39,240 --> 01:00:41,560 1 IN 4 WOMEN ARE GOING TO GO ON 1647 01:00:41,560 --> 01:00:43,280 TO DEVELOP BREAST CANCER-RELATED 1648 01:00:43,280 --> 01:00:43,800 LYMPHEDEMA. 1649 01:00:43,800 --> 01:00:43,960 WHY? 1650 01:00:43,960 --> 01:00:44,920 THAT'S THE QUESTION THAT KEEPS 1651 01:00:44,920 --> 01:00:45,360 ME UP. 1652 01:00:45,360 --> 01:00:50,600 WHY ARE 2 OUT OF 3 OR 3 OUT OF ? 1653 01:00:50,600 --> 01:00:51,640 THIS IS CRITICAL AND I THINK 1654 01:00:51,640 --> 01:00:52,880 THIS WOULD BE A COMPLETE 1655 01:00:52,880 --> 01:00:54,680 CLINICAL PARADIGM SHIFT. 1656 01:00:54,680 --> 01:00:57,560 THERE'S OFTEN A LOT OF 1657 01:00:57,560 --> 01:00:58,440 DISCUSSION, HEALTHY IMPORTANT 1658 01:00:58,440 --> 01:01:02,760 DISCUSSION OF SHOULD WELL DO AN 1659 01:01:02,760 --> 01:01:03,760 AXILLA RESECTION, SHOULD WE DO 1660 01:01:03,760 --> 01:01:04,400 REGIONAL RADIATION. 1661 01:01:04,400 --> 01:01:06,720 I THINK IF YOU HAD A LYMPHATIC 1662 01:01:06,720 --> 01:01:07,360 EXPERT SITTING IN THE CONFERENCE 1663 01:01:07,360 --> 01:01:09,000 ROOM AND YOU WERE ABLE TO SAY, 1664 01:01:09,000 --> 01:01:11,960 LOOK, THIS PATIENT'S INDIVIDUAL 1665 01:01:11,960 --> 01:01:13,920 RISK AGAIN OF LYMPHEDEMA IS 1666 01:01:13,920 --> 01:01:15,200 100%, THAT MY VERY MUCH SHIFT 1667 01:01:15,200 --> 01:01:16,960 THE DISCUSSION IN THAT ROOM IN 1668 01:01:16,960 --> 01:01:18,280 FAVOR OF THE PATIENT AND 1669 01:01:18,280 --> 01:01:19,880 HOPEFULLY PREVENTING THE 1670 01:01:19,880 --> 01:01:20,240 DISEASE. 1671 01:01:20,240 --> 01:01:23,040 SO WHAT IS THE -- WHY ARE -- 1672 01:01:23,040 --> 01:01:24,240 WHAT'S THE INDIVIDUAL RISK FOR A 1673 01:01:24,240 --> 01:01:26,640 PATIENT GETTING BREAST CANCER 1674 01:01:26,640 --> 01:01:27,240 RELATED LYMPHEDEMA? 1675 01:01:27,240 --> 01:01:28,480 IF YOU GO INTO THE LITERATURE, 1676 01:01:28,480 --> 01:01:29,800 YOU'RE GOING TO FIND TWO BASIC 1677 01:01:29,800 --> 01:01:30,240 SCHOOLS. 1678 01:01:30,240 --> 01:01:32,640 ONE IS THAT IT'S GENETIC AND 1679 01:01:32,640 --> 01:01:34,120 ANOTHER ONE IS THAT THERE'S 1680 01:01:34,120 --> 01:01:34,920 ANATOMIC VARIATION. 1681 01:01:34,920 --> 01:01:38,520 WHEN I STARTED TALKING ABOUT 1682 01:01:38,520 --> 01:01:40,880 THIS, I SAID IT ALL ABOUT 1683 01:01:40,880 --> 01:01:41,120 ANATOMY. 1684 01:01:41,120 --> 01:01:42,560 I STILL BELIEVE ANATOMY IS 1685 01:01:42,560 --> 01:01:44,160 DRIVING THIS BUT I DO THINK 1686 01:01:44,160 --> 01:01:45,200 GENETICS PLAY A ROLE AND I'LL 1687 01:01:45,200 --> 01:01:45,960 TALK ABOUT WHERE I THINK THAT 1688 01:01:45,960 --> 01:01:50,160 MIGHT BE THE CASE. 1689 01:01:50,160 --> 01:01:52,040 SO THE KEY THING ABOUT ANATOMY, 1690 01:01:52,040 --> 01:01:58,120 IT WAS BROUGHT UP IN INTERDUCK 1691 01:01:58,120 --> 01:02:00,720 INTRODUCTORY REMARKS YESTERDAY, 1692 01:02:00,720 --> 01:02:06,280 THE LATEST COMPENDIUM -- IF YOU 1693 01:02:06,280 --> 01:02:09,560 GO BACK TO THIS ORIGINAL PANEL 1694 01:02:09,560 --> 01:02:12,200 FROM SAPPEY IN 1874, YOU CAN SEE 1695 01:02:12,200 --> 01:02:16,320 THE MAJORITY OF THE ARM 1696 01:02:16,320 --> 01:02:18,280 LYMPHATICS PRETTY EXCELLENT. 1697 01:02:18,280 --> 01:02:19,760 BUT HERE WITH THE RED ARROW, YOU 1698 01:02:19,760 --> 01:02:22,400 CAN SEE THE PATHWAY COMPLETELY 1699 01:02:22,400 --> 01:02:25,040 AVOIDING THE AXILLA. 1700 01:02:25,040 --> 01:02:28,440 THIS IS SOMETIMES TERMED THE 1701 01:02:28,440 --> 01:02:30,920 LATERAL UPPER ARM PATHWAY, 1702 01:02:30,920 --> 01:02:32,440 SAPPEY PATHWAY, IT HAS A LOT OF 1703 01:02:32,440 --> 01:02:33,880 NAMES, BUT THIS MIGHT BE 1704 01:02:33,880 --> 01:02:36,720 PROTECTED IF SOMEBODY UNDERGOES 1705 01:02:36,720 --> 01:02:39,080 AN AXILLA RESECTION AND THIS 1706 01:02:39,080 --> 01:02:39,960 PATHWAY IS PRESENT. 1707 01:02:39,960 --> 01:02:41,080 SO OUR TEAM GOT INTERESTED IN 1708 01:02:41,080 --> 01:02:42,520 THIS AND REALLY STARTED LOOKING 1709 01:02:42,520 --> 01:02:45,760 AT THIS A FEW YEARS AGO, AND THE 1710 01:02:45,760 --> 01:02:47,400 ANATOMISTS MADE IT CLEAR THAT 1711 01:02:47,400 --> 01:02:51,200 THIS PATHWAY IS REALLY RIGHT 1712 01:02:51,200 --> 01:02:53,160 ADJACENT TO THE CEPHALIC VEIN SO 1713 01:02:53,160 --> 01:02:54,480 USING THE CEPHALIC VEIN AS A 1714 01:02:54,480 --> 01:02:56,280 MARKER, USING ULTRASOUND WE 1715 01:02:56,280 --> 01:02:58,160 INJECT A DYE INTO THE SKIN SO WE 1716 01:02:58,160 --> 01:02:59,480 GET IT INTO THE LYMPHATIC 1717 01:02:59,480 --> 01:03:02,640 SYSTEM, AND YOU CAN SEE ON THIS 1718 01:03:02,640 --> 01:03:05,280 WITH LYMPHATICS TRULY RIDING 1719 01:03:05,280 --> 01:03:06,240 ALMOST RIGHT ALONG THE VEIN. 1720 01:03:06,240 --> 01:03:10,640 THERE'S A LOT OF WAYS TO SHOW 1721 01:03:10,640 --> 01:03:14,960 THIS. 1722 01:03:14,960 --> 01:03:16,840 SUAMI CAME WITH THIS BEAUTIFUL 1723 01:03:16,840 --> 01:03:18,600 DISSECTION OF LYMPHATICS, BUT 1724 01:03:18,600 --> 01:03:20,760 HERE'S THE BACKUP. 1725 01:03:20,760 --> 01:03:22,400 THE M-S PATHWAY. 1726 01:03:22,400 --> 01:03:23,800 HERE'S IMAGING IN OUR OWN CLINIC 1727 01:03:23,800 --> 01:03:25,560 WE CAN DO PREOPERATIVELY ON A 1728 01:03:25,560 --> 01:03:27,320 NEWLY DIAGNOSED BREAST CANCER 1729 01:03:27,320 --> 01:03:29,160 PATIENT, WHERE WE CAN DEFINE 1730 01:03:29,160 --> 01:03:31,600 THIS, WE CAN DEFINE THEIR M-S 1731 01:03:31,600 --> 01:03:32,640 PATHWAY AND ITS PRESENCE OR 1732 01:03:32,640 --> 01:03:33,200 ABSENCE. 1733 01:03:33,200 --> 01:03:36,680 AND WHAT WE'VE SHOWN IN VIVO IS 1734 01:03:36,680 --> 01:03:38,880 WHAT ANATOMISTS HAVE SHOWN IN 1735 01:03:38,880 --> 01:03:42,360 CADAVERS YEARS AGO, DECADES AGO, 1736 01:03:42,360 --> 01:03:43,560 IN THAT THERE'S VARIATIONS IN 1737 01:03:43,560 --> 01:03:45,280 THIS PATHWAY, WHAT WE CALL A 1738 01:03:45,280 --> 01:03:47,160 LONG BUNDLE AND A SHORT BUNDLE. 1739 01:03:47,160 --> 01:03:49,240 A LONG BUNDLE IS WHERE THIS 1740 01:03:49,240 --> 01:03:50,880 PATHWAY EXISTS AND IT TRAVELS 1741 01:03:50,880 --> 01:03:52,360 THROUGHOUT THE ARM, WHICH IS 1742 01:03:52,360 --> 01:03:53,560 PROBABLY FAVORABLE BECAUSE AT 1743 01:03:53,560 --> 01:03:57,400 THIS OTHER MAIN PATHWAY, THE 1744 01:03:57,400 --> 01:04:00,000 AXILLA GETS WIPED OUT AFTER AN 1745 01:04:00,000 --> 01:04:01,000 AXILLA DISSECTION, THE ENTIRE 1746 01:04:01,000 --> 01:04:03,000 ARM CAN PROBABLY USE THIS AS A 1747 01:04:03,000 --> 01:04:03,720 BACKUP. 1748 01:04:03,720 --> 01:04:05,680 HERE YOU HAVE WHAT WE CALL A 1749 01:04:05,680 --> 01:04:06,760 SHORT BUNDLE WHERE YOU INJECT IN 1750 01:04:06,760 --> 01:04:08,080 THE HAND FIRST AND ACTUALLY 1751 01:04:08,080 --> 01:04:09,440 NOTHING LIGHTS UP OUT HERE WITH 1752 01:04:09,440 --> 01:04:13,120 A LATERAL UPPER AND -- YOU HAVE 1753 01:04:13,120 --> 01:04:15,680 TO DO AN INJECTION HERE TO SEE 1754 01:04:15,680 --> 01:04:16,000 IT. 1755 01:04:16,000 --> 01:04:17,280 YOU CAN IMAGINE IN THIS PATIENT 1756 01:04:17,280 --> 01:04:18,920 THAT THIS MAIN PATHWAY GETS 1757 01:04:18,920 --> 01:04:20,080 WIPED OUT, YOU HAVE THIS 1758 01:04:20,080 --> 01:04:21,240 WATERSHED AREA, AND THIS IS 1759 01:04:21,240 --> 01:04:25,040 WHERE GENETICS MAY PLAY A ROLE 1760 01:04:25,040 --> 01:04:26,600 IN SOME PATIENTS REGENERATING 1761 01:04:26,600 --> 01:04:27,240 FASTER THAN OTHERS. 1762 01:04:27,240 --> 01:04:28,440 HERE'S A QUICK VIDEO SHOWING 1763 01:04:28,440 --> 01:04:29,640 WHAT THIS LOOKS LIKE. 1764 01:04:29,640 --> 01:04:31,720 SO THIS IS, AGAIN, WE CAN DO 1765 01:04:31,720 --> 01:04:33,680 THIS IN OUR CLINIC, WE INJECT 1766 01:04:33,680 --> 01:04:35,000 THE HAND FIRST AND RIGHT AWAY, 1767 01:04:35,000 --> 01:04:36,920 YOU CAN SEE BOTH PATHWAYS ARE 1768 01:04:36,920 --> 01:04:37,200 SHOWING UP. 1769 01:04:37,200 --> 01:04:39,000 WE HAVE OUR MAIN PATHWAY HERE 1770 01:04:39,000 --> 01:04:41,720 GOING TO THE AXILLA, AND THERE'S 1771 01:04:41,720 --> 01:04:43,640 A BACKUP PATHWAY, HERE IT IS, 1772 01:04:43,640 --> 01:04:45,840 IT'S CONNECTED TO THE FOREARM. 1773 01:04:45,840 --> 01:04:47,800 THIS IS FAVORABLE. 1774 01:04:47,800 --> 01:04:48,560 NOW I'LL SHOW YOU WHAT IT LOOKS 1775 01:04:48,560 --> 01:04:50,000 LIKE IN A SHORT BUNDLE BETTER. 1776 01:04:50,000 --> 01:04:51,840 SO WE INJECT THE HAND AND 1777 01:04:51,840 --> 01:04:52,880 ACTUALLY NOTHING LIGHTS UP HERE. 1778 01:04:52,880 --> 01:04:55,440 WE HAVE TO DO A SECOND INJECTION 1779 01:04:55,440 --> 01:04:57,720 UP HERE TO MAKE THESE OTHER 1780 01:04:57,720 --> 01:05:02,440 PATHWAYS LIGHT UP. 1781 01:05:02,440 --> 01:05:04,200 AND HERE'S YOUR WATERSHED AREA, 1782 01:05:04,200 --> 01:05:05,800 ASSUMING THESE PATHWAYS GO AWAY 1783 01:05:05,800 --> 01:05:16,320 AFTER AN AXILLARY DISSECTION. 1784 01:05:16,840 --> 01:05:22,360 SO WE LOOKED AT PATIENTS AND 1785 01:05:22,360 --> 01:05:23,000 ESSENTIALLY TWO THIRDS HAVE A 1786 01:05:23,000 --> 01:05:27,120 LONG BUNDLE, WHICH WE BELIEVE IS 1787 01:05:27,120 --> 01:05:31,840 GOOD, A THIRD HAS A SHORT BUNDLE 1788 01:05:31,840 --> 01:05:33,840 AND STARTING TO NOTICE THE 1789 01:05:33,840 --> 01:05:35,760 PRESENCE OF LYMPHEDEMA AND VERY 1790 01:05:35,760 --> 01:05:38,520 FEW ACTUALLY HAVE NO BUNDLE AT 1791 01:05:38,520 --> 01:05:39,160 ALL. 1792 01:05:39,160 --> 01:05:40,480 WHAT WE NOTICED IS EVEN THOUGH 1793 01:05:40,480 --> 01:05:42,920 THE SHORT BUNDLE, WHICH IS 1794 01:05:42,920 --> 01:05:44,320 UNFAVORABLE, ONLY MADE UP 1795 01:05:44,320 --> 01:05:45,840 ONE-THIRD OF OUR COHORT, IT MADE 1796 01:05:45,840 --> 01:05:47,680 UP TWO THIRDS OF THOSE PATIENTS 1797 01:05:47,680 --> 01:05:50,280 WHO POST OP DEVELOPED ANYTHING 1798 01:05:50,280 --> 01:05:50,960 CONSISTENT WITH LYMPHEDEMA. 1799 01:05:50,960 --> 01:05:53,040 I WON'T SAY THEY HAD A DIAGNOSIS 1800 01:05:53,040 --> 01:05:54,480 OF LYMPHEDEMA BECAUSE WE HAD 1801 01:05:54,480 --> 01:05:56,840 PRETTY STRICT CRITERIA AND THEY 1802 01:05:56,840 --> 01:05:58,480 MIGHT NOT HAVE FIT ALL THE 1803 01:05:58,480 --> 01:05:59,240 CRITERIA, BUT THEY HAD ENOUGH 1804 01:05:59,240 --> 01:06:00,960 THAT WE WERE CONCERNED AND WE 1805 01:06:00,960 --> 01:06:02,600 MIGHT HAVE EVEN INTERVENED. 1806 01:06:02,600 --> 01:06:04,800 SO FORTUNATELY WITH THIS DATA 1807 01:06:04,800 --> 01:06:05,960 AND THIS EXPERIENCE, WE WERE 1808 01:06:05,960 --> 01:06:08,320 FORTUNATE TO GET FUNDING FROM 1809 01:06:08,320 --> 01:06:09,800 THE NIH/NHLBI TO DO FURTHER 1810 01:06:09,800 --> 01:06:13,600 STUDY ON THIS PATHWAY, WHERE 1811 01:06:13,600 --> 01:06:14,480 WE'RE DEFINING ITS INCIDENCE IN 1812 01:06:14,480 --> 01:06:16,400 A HEALTHY FEMALE POPULATION, AS 1813 01:06:16,400 --> 01:06:17,800 WELL AS BREAST CANCER SURVIVORS 1814 01:06:17,800 --> 01:06:21,600 WHO DID NOT GET LYMPHEDEMA AND 1815 01:06:21,600 --> 01:06:23,560 WE ALSO HAVE AN ANIMAL MODEL 1816 01:06:23,560 --> 01:06:26,280 WHERE WE WERE LOOKING AT 1817 01:06:26,280 --> 01:06:27,840 LYMPHATIC FUNCTION AND MAPPING. 1818 01:06:27,840 --> 01:06:30,800 I JUST WANTED TO SHOW SOME 1819 01:06:30,800 --> 01:06:31,760 IMAGES FROM PATIENTS THAT ARE 1820 01:06:31,760 --> 01:06:33,720 GOING THROUGH RIGHT NOW, THROUGH 1821 01:06:33,720 --> 01:06:36,360 OUR R01 MECHANISM, AND WHAT WE 1822 01:06:36,360 --> 01:06:39,520 ARE DOING, WHAT YOU ARE NOT 1823 01:06:39,520 --> 01:06:42,920 SEEING HERE, WE'RE TAKING OUR 1824 01:06:42,920 --> 01:06:43,920 IMAGING AND BASED ON THE ZONE 1825 01:06:43,920 --> 01:06:48,280 WHERE WE INITIALLY INJECTED, WE 1826 01:06:48,280 --> 01:06:49,800 IS A LYMPHOZONE CONCEPT 1827 01:06:49,800 --> 01:06:51,560 INTRODUCED BY SUAMI, YOU SEE 1828 01:06:51,560 --> 01:06:53,000 DIFFERENT COLORS. 1829 01:06:53,000 --> 01:06:54,280 DIFFERENT COLORS REPRESENT 1830 01:06:54,280 --> 01:06:54,680 DIFFERENT ZONES. 1831 01:06:54,680 --> 01:06:57,800 I WANT TO POINT OUT THIS LATERAL 1832 01:06:57,800 --> 01:06:59,000 UPPER ARM PATHWAY AND I WANT YOU 1833 01:06:59,000 --> 01:07:00,000 TO SEE THAT IN DIFFERENT 1834 01:07:00,000 --> 01:07:01,840 PATIENTS, WE ARE FINDING THAT 1835 01:07:01,840 --> 01:07:03,160 THEY HAVE DIFFERENT 1836 01:07:03,160 --> 01:07:04,280 CONTRIBUTIONS IN DIFFERENT 1837 01:07:04,280 --> 01:07:05,920 ZONES, AND ULTIMATELY, WE 1838 01:07:05,920 --> 01:07:08,720 BELIEVE THIS IS GOING TO PLAY AN 1839 01:07:08,720 --> 01:07:10,400 IMPORTANT -- IT'S GOING TO HELP 1840 01:07:10,400 --> 01:07:12,000 FILL IN THE GAP OF WHY CERTAIN 1841 01:07:12,000 --> 01:07:13,800 WOMEN ARE GETTING LYMPHEDEMA AND 1842 01:07:13,800 --> 01:07:16,400 OTHERS ARE NOT AFTER AN AXILLARY 1843 01:07:16,400 --> 01:07:17,280 NODE DISSECTION. 1844 01:07:17,280 --> 01:07:18,720 WE'RE BACKING THIS UP WITH 1845 01:07:18,720 --> 01:07:19,720 NUCLEAR INJECTIONS IN THESE 1846 01:07:19,720 --> 01:07:21,160 DIFFERENT ZONES, AND HERE WE 1847 01:07:21,160 --> 01:07:22,880 HAVE ISOLATED INJECTIONS IN THIS 1848 01:07:22,880 --> 01:07:26,600 ONE VOLUNTEER RIGHT OVER THE M-S 1849 01:07:26,600 --> 01:07:28,000 PATHWAY, WHERE YOU CAN SEE EVEN 1850 01:07:28,000 --> 01:07:30,280 BETWEEN LEFT AND RIGHT, THERE'S 1851 01:07:30,280 --> 01:07:31,640 VARIABILITY ON WHICH NODE LIGHT 1852 01:07:31,640 --> 01:07:33,920 UP, VERSUS IN THIS IMAGE, THEY 1853 01:07:33,920 --> 01:07:35,880 COME BACK A FEW DAYS LATER, 1854 01:07:35,880 --> 01:07:38,520 AFTER THE TECHNICIANS -- WE DO 1855 01:07:38,520 --> 01:07:40,080 SEPARATE INJECTIONS, HERE WE DO 1856 01:07:40,080 --> 01:07:42,360 IT IN THE HAND AND YOU CAN SEE 1857 01:07:42,360 --> 01:07:43,120 DIFFERENT LYMPH NODES ARE 1858 01:07:43,120 --> 01:07:43,560 LIGHTING UP. 1859 01:07:43,560 --> 01:07:45,120 SO THIS IS REALLY IMPORTANT AS 1860 01:07:45,120 --> 01:07:47,080 WE'RE TRYING TO TEASE OUT TRULY 1861 01:07:47,080 --> 01:07:49,040 THE ENTIRE PATH, NOT ONLY IN THE 1862 01:07:49,040 --> 01:07:50,120 ARM, BUT WHERE DOES THIS GO INTO 1863 01:07:50,120 --> 01:07:51,000 THE TORSO? 1864 01:07:51,000 --> 01:07:53,720 WE'VE BEEN REALLY FORTUNATE THIS 1865 01:07:53,720 --> 01:07:55,600 SUMMER TO RECEIVE FURTHER 1866 01:07:55,600 --> 01:07:57,880 FUNDING AS PART OF THE 1867 01:07:57,880 --> 01:07:59,400 INCREDIBLE HUBMAP PROGRAM AT THE 1868 01:07:59,400 --> 01:08:01,280 NIH, AND WE'VE PUT TOGETHER A 1869 01:08:01,280 --> 01:08:09,920 TEAM REALLY LED BY MYSELF, 1870 01:08:09,920 --> 01:08:11,880 GIANNIS, SPATIAL TECHNOLOGY UNIT 1871 01:08:11,880 --> 01:08:15,280 WHERE WE'RE GOING TO DO MAPPING 1872 01:08:15,280 --> 01:08:16,720 OF THE HUMAN LYMPHATIC VESSELS 1873 01:08:16,720 --> 01:08:18,240 AND THE GOAL IS TO DO IT 1874 01:08:18,240 --> 01:08:20,080 ULTIMATELY THROUGHOUT THE HUMAN 1875 01:08:20,080 --> 01:08:21,840 BODY AND HOPEFULLY THROUGHOUT 1876 01:08:21,840 --> 01:08:22,800 ALL ORGANS. 1877 01:08:22,800 --> 01:08:27,760 WE'RE GOING TO BE OBTAINING 3D 1878 01:08:27,760 --> 01:08:28,760 MRLs, ULTIMATELY TAKING THESE 1879 01:08:28,760 --> 01:08:30,520 VOLUNTEERS TO THE O.R., TAKING 1880 01:08:30,520 --> 01:08:33,400 OUT A SEGMENT THAT'S PREDEFINED 1881 01:08:33,400 --> 01:08:36,280 IN THE MRL, AND THEN DOING 1882 01:08:36,280 --> 01:08:40,760 SPATIAL ANALYSIS ON IT, 1883 01:08:40,760 --> 01:08:41,880 REGISTERING BIOMOLECULAR ASSAYS 1884 01:08:41,880 --> 01:08:44,920 BACK TO OUR 3D MRI. 1885 01:08:44,920 --> 01:08:47,080 SO WITH THAT, IN CONCLUSION, YOU 1886 01:08:47,080 --> 01:08:49,800 KNOW, I BELIEVE ILR REDUCES 1887 01:08:49,800 --> 01:08:50,920 LYMPHEDEMA INCIDENCE, AND I 1888 01:08:50,920 --> 01:08:52,240 THINK LYMPHATIC ANATOMY STUDY IS 1889 01:08:52,240 --> 01:08:54,320 GOING TO BE CRITICAL FOR THE 1890 01:08:54,320 --> 01:08:55,760 FUTURE OF THIS FIELD, NOT ONLY 1891 01:08:55,760 --> 01:08:57,160 FOR PREVENTION BUT I BELIEVE 1892 01:08:57,160 --> 01:08:58,720 WE'LL BE ABLE TO REVERSE 1893 01:08:58,720 --> 01:09:02,320 ENGINEER SOLUTIONS ONCE WE 1894 01:09:02,320 --> 01:09:03,840 UNDERSTAND WHERE THE ANATOMIC 1895 01:09:03,840 --> 01:09:05,600 GAPS ARE, WE'LL BE ABLE TO 1896 01:09:05,600 --> 01:09:09,000 BETTER DECIDE ON HOW WE SHOULD 1897 01:09:09,000 --> 01:09:09,800 APPROACH PATIENTS THAT ALREADY 1898 01:09:09,800 --> 01:09:12,200 HAVE THE DISEASE SURGICALLY, IN 1899 01:09:12,200 --> 01:09:12,680 OTHER WORDS. 1900 01:09:12,680 --> 01:09:13,720 GAPS, NEED AND OPPORTUNITIES, 1901 01:09:13,720 --> 01:09:15,880 HOW CAN WE STRATEGIZE FURTHER TO 1902 01:09:15,880 --> 01:09:18,280 IMPROVE THE SURGICAL TECHNIQUE 1903 01:09:18,280 --> 01:09:19,040 AND SURGICAL PREVENTION OF 1904 01:09:19,040 --> 01:09:19,880 LYMPHEDEMA? 1905 01:09:19,880 --> 01:09:20,720 NUMBER TWO, AND THIS IS THE ONE 1906 01:09:20,720 --> 01:09:21,760 THAT I REALLY THINK ABOUT ALL 1907 01:09:21,760 --> 01:09:23,400 THE TIME, WHAT ARE THE MAIN 1908 01:09:23,400 --> 01:09:24,920 LYMPHATIC ANATOMY VARIANTS OF 1909 01:09:24,920 --> 01:09:26,680 THE UPPER EXTREMITY, AND THEN 1910 01:09:26,680 --> 01:09:29,320 THE COROLLARY IS, HOW DO THE 1911 01:09:29,320 --> 01:09:31,720 PRESENCE OR ABSENCE OF EACH 1912 01:09:31,720 --> 01:09:32,560 VARIANT CONTRIBUTE TO THE 1913 01:09:32,560 --> 01:09:33,160 INCIDENCE OF LYMPHEDEMA? 1914 01:09:33,160 --> 01:09:35,640 I WANT TO THANK THE CLINICAL 1915 01:09:35,640 --> 01:09:37,760 TEAM HERE, AT THE BOSTON 1916 01:09:37,760 --> 01:09:42,160 LYMPHATIC 16 TE THE RESEARCH CEH 1917 01:09:42,160 --> 01:09:42,400 TEAM. 1918 01:09:42,400 --> 01:09:45,680 WE HAVE INCREDIBLE SUPPORT FROM 1919 01:09:45,680 --> 01:09:51,680 THE NIH, THE JOBST LYMPHATIC 1920 01:09:51,680 --> 01:09:52,760 RESEARCH GRANT HAS A 1921 01:09:52,760 --> 01:09:56,320 SCHOLARSHIP, I WANT TO THANK OUR 1922 01:09:56,320 --> 01:09:57,360 COLLABORATORS, ESPECIALLY TIM, 1923 01:09:57,360 --> 01:09:59,720 FOR THOSE WHO ARE INTERESTED, WE 1924 01:09:59,720 --> 01:10:01,600 RUN OUR OWN SYMPOSIUM, AND OUR 1925 01:10:01,600 --> 01:10:02,520 NEXT CLINICAL AND RESEARCH 1926 01:10:02,520 --> 01:10:03,960 PROGRAM WILL BE IN 2023. 1927 01:10:03,960 --> 01:10:09,400 THANK YOU AGAIN. 1928 01:10:09,400 --> 01:10:10,040 >> AWESOME. 1929 01:10:10,040 --> 01:10:11,880 THANK YOU SO MUCH, DREW, FOR 1930 01:10:11,880 --> 01:10:12,760 THAT WONDERFUL PRESENTATION. 1931 01:10:12,760 --> 01:10:13,760 WE WILL HAVE YOUR QUESTIONS AT 1932 01:10:13,760 --> 01:10:15,120 THE END OF THE WHOLE SESSION AND 1933 01:10:15,120 --> 01:10:18,080 I'VE ALREADY SEEN SOP STARTING G 1934 01:10:18,080 --> 01:10:19,400 TO COME IN, SO HE WITH LOOK 1935 01:10:19,400 --> 01:10:20,280 FORWARD TO BE ABLE TO HAVE THAT 1936 01:10:20,280 --> 01:10:23,320 DISCUSSION WITH YOU THEN. 1937 01:10:23,320 --> 01:10:25,520 SO NEXT I AM HONORED TO 1938 01:10:25,520 --> 01:10:28,480 INTRODUCE OUR NEXT SPEAKER, WHO 1939 01:10:28,480 --> 01:10:30,320 IS MARC SCHAVERIEN. 1940 01:10:30,320 --> 01:10:31,320 MARC, IF YOU WANT TO PULL UP 1941 01:10:31,320 --> 01:10:32,160 YOUR SLIDES. 1942 01:10:32,160 --> 01:10:35,920 MARC IS FROM THE MD ANDERSON 1943 01:10:35,920 --> 01:10:37,560 CANCER CENTER, TELLING US ABOUT 1944 01:10:37,560 --> 01:10:39,760 OUTCOMES OF VASCULARIZED LYMPH 1945 01:10:39,760 --> 01:10:41,480 NODE TRANSPLANT FOR LYMPHEDEMA 1946 01:10:41,480 --> 01:10:41,920 TREATMENT. 1947 01:10:41,920 --> 01:10:43,240 MARC, THE FLOOR IS YOURS. 1948 01:10:43,240 --> 01:10:44,320 >> THANK YOU VERY MUCH INDEED, 1949 01:10:44,320 --> 01:10:44,720 TIM. 1950 01:10:44,720 --> 01:10:46,000 CAN I JUST CHECK, YOU CAN HEAR 1951 01:10:46,000 --> 01:10:47,080 ME AND SEE MY SLIDES? 1952 01:10:47,080 --> 01:10:48,360 >> WE SEE YOUR SLIDES AND HEAR 1953 01:10:48,360 --> 01:10:48,680 YOU WELL. 1954 01:10:48,680 --> 01:10:49,080 THANK YOU. 1955 01:10:49,080 --> 01:10:49,680 >> PERFECT. 1956 01:10:49,680 --> 01:10:51,440 THANK YOU. 1957 01:10:51,440 --> 01:10:55,400 WELL, IT'S A REAL HONOR TO BE 1958 01:10:55,400 --> 01:10:56,880 PART OF THIS MEETING. 1959 01:10:56,880 --> 01:10:58,280 IT'S BEEN A REALLY FASCINATING 1960 01:10:58,280 --> 01:10:58,600 TWO DAYS. 1961 01:10:58,600 --> 01:11:00,000 I'M LEARNING A LOT. 1962 01:11:00,000 --> 01:11:02,400 I HAVE A BOOK BUT I DON'T ACCEPT 1963 01:11:02,400 --> 01:11:04,480 FEES OR ROYALTIES. 1964 01:11:04,480 --> 01:11:05,760 AND TODAY I'M GOING TO TALK TO 1965 01:11:05,760 --> 01:11:08,080 YOU ABOUT VASCULARIZED LYMPH 1966 01:11:08,080 --> 01:11:09,840 NODE TRANSPLANTATION WHICH IS 1967 01:11:09,840 --> 01:11:11,040 REALLY THE PREDOMINANT VIABLE 1968 01:11:11,040 --> 01:11:12,120 TREATMENT WE HAVE FOR 1969 01:11:12,120 --> 01:11:12,600 ESTABLISHED LYMPHEDEMA. 1970 01:11:12,600 --> 01:11:14,320 I ALSO WANT TO TALK ABOUT AN 1971 01:11:14,320 --> 01:11:17,360 APPROACH THAT WE HAVE FOR 1972 01:11:17,360 --> 01:11:19,120 PREOPERATIVE OPTIMIZATION WHICH 1973 01:11:19,120 --> 01:11:23,920 SEEMS TO REALLY IMPROVE OUTCOMES 1974 01:11:23,920 --> 01:11:24,440 FROM THIS. 1975 01:11:24,440 --> 01:11:26,000 SO AS WE ALL KNOW AND THIS IS 1976 01:11:26,000 --> 01:11:30,040 WHY WE'RE HERE AT THIS MEETING, 1977 01:11:30,040 --> 01:11:33,400 LYMPHEDEMA IS A SEVERE CHRONIC 1978 01:11:33,400 --> 01:11:35,800 PROGRESSIVE DEBILITATING DISEASE 1979 01:11:35,800 --> 01:11:37,800 FOR PATIENTS CHARACTERIZED IN 1980 01:11:37,800 --> 01:11:40,040 ITS ADVANCED FORMS BY THIS 1981 01:11:40,040 --> 01:11:41,720 CHRONIC PHENOTYPE OF 1982 01:11:41,720 --> 01:11:44,200 PREDOMINANTLY FIBER ADIPOSE 1983 01:11:44,200 --> 01:11:46,280 EXCESS CHARACTERIZED BY CHRONIC 1984 01:11:46,280 --> 01:11:47,800 INFECTIONS. 1985 01:11:47,800 --> 01:11:50,000 AND VASCULARIZED LYMPH NODE 1986 01:11:50,000 --> 01:11:51,000 TRANSPLANTATION, ALTHOUGH IT'S 1987 01:11:51,000 --> 01:11:53,800 BEEN AROUND FOR QUITE SOME TIME, 1988 01:11:53,800 --> 01:11:57,640 IT'S ONLY RECENTLY THAT WE'VE 1989 01:11:57,640 --> 01:11:58,840 ESTABLISHED QUITE A BODY OF 1990 01:11:58,840 --> 01:12:00,040 EVIDENCE SUPPORTING ITS 1991 01:12:00,040 --> 01:12:00,640 EFFECTIVENESS. 1992 01:12:00,640 --> 01:12:01,760 BUT WHEN WE LOOK AT THE DATA 1993 01:12:01,760 --> 01:12:04,360 THAT'S AVAILABLE, THERE ARE 1994 01:12:04,360 --> 01:12:08,240 THREE SYSTEMATIC REVIEWS THAT 1995 01:12:08,240 --> 01:12:09,320 DEMONSTRATE IMPROVEMENT IN 1996 01:12:09,320 --> 01:12:10,520 VOLUME REDUCTION, PATIENT 1997 01:12:10,520 --> 01:12:12,560 SYMPTOMS, QUALITY OF LIFE 1998 01:12:12,560 --> 01:12:16,840 REDUCTION OF IB FECTED INF. 1999 01:12:16,840 --> 01:12:18,160 WHEN WE COMPARE THE RESULTS OF 2000 01:12:18,160 --> 01:12:20,320 SURGERY WITH THOSE OF 2001 01:12:20,320 --> 01:12:20,960 CONSERVATIVE THERAPY ONLY, 2002 01:12:20,960 --> 01:12:22,400 INCLUDING IN A RANDOMIZED 2003 01:12:22,400 --> 01:12:24,920 CONTROL TRIAL, THERE ARE 2004 01:12:24,920 --> 01:12:25,680 IMPROVEMENTS, SIGNIFICANT 2005 01:12:25,680 --> 01:12:27,320 IMPROVEMENTS FROM SURGERY WHEN 2006 01:12:27,320 --> 01:12:29,200 COMPARED WITH CONSERVATIVE 2007 01:12:29,200 --> 01:12:29,960 THERAPY ALONE. 2008 01:12:29,960 --> 01:12:31,040 SO THE APPROACH I'M GOING TO 2009 01:12:31,040 --> 01:12:34,760 DISCUSS WITH YOU TODAY IS FROM 2010 01:12:34,760 --> 01:12:35,440 MD ANDERSON. 2011 01:12:35,440 --> 01:12:38,120 IT'S REALLY IMPORTANT TO HAVE A 2012 01:12:38,120 --> 01:12:40,080 MULTIMODAL METHOD FOR PATIENT 2013 01:12:40,080 --> 01:12:41,840 EVALUATION, AS NOT ONE MODE IS 2014 01:12:41,840 --> 01:12:45,320 OPTIMAL OR RELIABLE FOR 2015 01:12:45,320 --> 01:12:48,800 DIAGNOSIS, FOE KUTIONING Y 2016 01:12:48,800 --> 01:12:49,480 AND CLINICAL EXADGES TO 2017 01:12:49,480 --> 01:12:51,360 DETERMINE THE PATIENT REALLY HAS 2018 01:12:51,360 --> 01:12:52,960 LYMPHEDEMA AS COMMONLY SWELLING 2019 01:12:52,960 --> 01:12:57,440 IS ATTRIBUTED TO OTHER 2020 01:12:57,440 --> 01:12:57,800 CONDITIONS. 2021 01:12:57,800 --> 01:12:59,080 A REALLY IMPORTANT PART OF THIS 2022 01:12:59,080 --> 01:13:02,240 AS DHRUV WAS JUST DISCUSSING IS 2023 01:13:02,240 --> 01:13:04,200 IMAGING, ICG IN PARTICULAR BUT 2024 01:13:04,200 --> 01:13:07,600 ALSO MAGNETIC RESONANCE 2025 01:13:07,600 --> 01:13:09,120 LYMPHOGRAPHY, IT'S IMPORTANT TO 2026 01:13:09,120 --> 01:13:12,280 STANDIZE MEASUREMENTS, WE USE A 2027 01:13:12,280 --> 01:13:14,040 PEROMETER, YOU CAN ALSO USE A 2028 01:13:14,040 --> 01:13:17,960 TAPE MEASURE, BIOIMPEDANCE 2029 01:13:17,960 --> 01:13:20,240 SPECTROSCOPY IS REALLY BECOME BG 2030 01:13:20,240 --> 01:13:21,800 A TOOL IN MEASURING THE FLUID 2031 01:13:21,800 --> 01:13:27,360 CHANGES IN THESE PATIENTS, AND 2032 01:13:27,360 --> 01:13:28,160 ALSO PATIENT-REPORTED OUTCOMES. 2033 01:13:28,160 --> 01:13:29,720 THERE ARE MANY DIFFERENT TOOLS. 2034 01:13:29,720 --> 01:13:35,400 WE USE THE NLIS. 2035 01:13:35,400 --> 01:13:38,200 THERE IS OFTEN A CO-MORBID 2036 01:13:38,200 --> 01:13:39,520 ELEMENT, MAY BE TREATED PRE-OP 2037 01:13:39,520 --> 01:13:40,640 PHILADELPHIA TO OPTIMIZE 2038 01:13:40,640 --> 01:13:43,760 OUTCOMES IN SURGERY, AND THAT 2039 01:13:43,760 --> 01:13:54,280 CAN BE -- BUT SIMPLY REQUIRES 2040 01:13:55,880 --> 01:13:56,640 VENOGRAPHY. 2041 01:13:56,640 --> 01:14:03,120 WE'RE EVALUATING THE THE DERML 2042 01:14:03,120 --> 01:14:03,560 BACKFLOW. 2043 01:14:03,560 --> 01:14:14,040 THIS IS THE MD ANDERSON SCALE, 2044 01:14:14,760 --> 01:14:16,880 RELIABLY -- IT'S IMPORTANT TO 2045 01:14:16,880 --> 01:14:19,160 CONFIRM THAT PATIENTS HAVE 2046 01:14:19,160 --> 01:14:21,800 LYMPHEDEMA THROUGH DIAGNOSTIC 2047 01:14:21,800 --> 01:14:23,120 LYMPHATIC IMAGING TO EXCLUDE 2048 01:14:23,120 --> 01:14:25,360 OTHER CAUSES OF LIMB SWELLING. 2049 01:14:25,360 --> 01:14:26,600 THOSE PATIENTS ARE POTENTIALLY 2050 01:14:26,600 --> 01:14:33,960 CANDIDATE FOR VASCULARIZED FLOW 2051 01:14:33,960 --> 01:14:34,360 TRANSPLANT. 2052 01:14:34,360 --> 01:14:36,640 PATIENTS WITH CANCER AREN'T 2053 01:14:36,640 --> 01:14:42,640 TYPICALLY CANDIDATES FOR THESE 2054 01:14:42,640 --> 01:14:43,640 THERAPIES, NOR THAT'S WITH 2055 01:14:43,640 --> 01:14:45,480 SEVERE UNTREATABLE VENOUS INFUF 2056 01:14:45,480 --> 01:14:48,240 SEE. 2057 01:14:48,240 --> 01:14:50,080 INSUFFICIENCY. 2058 01:14:50,080 --> 01:14:52,360 THESE SURGERIES ARE POTENTIALLY 2059 01:14:52,360 --> 01:14:53,480 LONG, AND PATIENTS MAY REQUIRE 2060 01:14:53,480 --> 01:14:56,320 RETURN TO THE O.R., SO IT'S 2061 01:14:56,320 --> 01:15:04,720 IMPORTANT TO OPTIMIZE CARDIOPULL 2062 01:15:04,720 --> 01:15:05,640 CARDIOPULMONARY ECOMORBIDDITIES. 2063 01:15:05,640 --> 01:15:07,880 PATIENT WITH HIGH OBESITYTIOUS 2064 01:15:07,880 --> 01:15:12,040 BE ON A WEIGHT-LOSS PROGRAM TO 2065 01:15:12,040 --> 01:15:19,120 LESSEN RISKS FROM SURGERY. 2066 01:15:19,120 --> 01:15:22,880 THIS IS HIS APPROACH TO SUCK 2067 01:15:22,880 --> 01:15:30,600 SHN-ASSISTED LIE 2068 01:15:30,600 --> 01:15:32,680 SUCTION-ASSISTED LIPECTOMY. 2069 01:15:32,680 --> 01:15:35,200 FROM THAT TRANSLATED THAT INTO 2070 01:15:35,200 --> 01:15:40,560 VASCULARIZED LYMPH NODE 2071 01:15:40,560 --> 01:15:41,680 TRANSPLANTATION, EVERY PATIENT 2072 01:15:41,680 --> 01:15:43,200 REQUIRES A SLIGHTLY DIFFERENT 2073 01:15:43,200 --> 01:15:44,080 APPROACH. 2074 01:15:44,080 --> 01:15:49,800 REALLY CENTRALLY, COMPLIANCE 2075 01:15:49,800 --> 01:15:51,600 WITH OPTIMIZED CUSTOM 2076 01:15:51,600 --> 01:15:52,840 CONSERVATIVE THERAPY, AIDS 2077 01:15:52,840 --> 01:15:54,440 PATIENT SELECTION, ALSO IT 2078 01:15:54,440 --> 01:15:55,520 IMPROVES THE CONDITIONS FOR 2079 01:15:55,520 --> 01:15:57,480 SURGERY BY TRANSITION TOWARDS 2080 01:15:57,480 --> 01:15:59,120 THE MAINTENANCE PHASE. 2081 01:15:59,120 --> 01:16:01,320 AND ALSO IT ALLOWS US TO 2082 01:16:01,320 --> 01:16:02,600 INDEPENDENTLY EVALUATE THE 2083 01:16:02,600 --> 01:16:04,720 OUTCOMES FROM SURGERY AS OPPOSED 2084 01:16:04,720 --> 01:16:06,880 FROM CONSERVATIVE THERAPY. 2085 01:16:06,880 --> 01:16:10,680 WEIGHT MANAGEMENT MAY REQUIRE 2086 01:16:10,680 --> 01:16:13,560 REFERRAL TO A NUTRITIONIST OR 2087 01:16:13,560 --> 01:16:15,800 DIETITIAN, SOMETIMES TO 2088 01:16:15,800 --> 01:16:17,560 BARIATRIC SURGEON. 2089 01:16:17,560 --> 01:16:19,520 WITH PATIENTS WITH FREQUENT 2090 01:16:19,520 --> 01:16:23,920 EPISODES OF CELLULITIS, IT MAY 2091 01:16:23,920 --> 01:16:27,400 BE NECESSARY TO GIVE 2092 01:16:27,400 --> 01:16:28,200 PERIOPERATIVE ANTIBIOTICS. 2093 01:16:28,200 --> 01:16:30,160 THIS IS TYPICALLY WHAT A PATIENT 2094 01:16:30,160 --> 01:16:31,560 WILL EMBARK ON. 2095 01:16:31,560 --> 01:16:33,200 WHEN THEY PRESENT, WE WILL 2096 01:16:33,200 --> 01:16:34,520 REDUCE THEM USING EITHER 2097 01:16:34,520 --> 01:16:36,040 BANDAGING OR SPECIALIZED 2098 01:16:36,040 --> 01:16:37,680 COMPRESSION GARMENTS UNTIL 2099 01:16:37,680 --> 01:16:39,880 THERE'S MINIMAL OR NO PITTING 2100 01:16:39,880 --> 01:16:40,400 EDEMA. 2101 01:16:40,400 --> 01:16:41,800 THEY ARE MAINTAINED TIM 2102 01:16:41,800 --> 01:16:43,560 TIPICALLY IN CUSTOM COMPRESSION 2103 01:16:43,560 --> 01:16:44,760 GARMENTS. 2104 01:16:44,760 --> 01:16:45,640 OCCASIONALLY PATIENTS CAN BE 2105 01:16:45,640 --> 01:16:48,040 MANAGED IN NON-CUSTOM GARMENTS. 2106 01:16:48,040 --> 01:16:50,640 SOMETIMES PATIENTS WILL ALSO GET 2107 01:16:50,640 --> 01:16:51,320 A PUMP. 2108 01:16:51,320 --> 01:16:52,400 IT IMPORTANT TO UNDERSTAND THESE 2109 01:16:52,400 --> 01:16:53,720 PATIENTS ARE VERY COMPLEX AND 2110 01:16:53,720 --> 01:16:56,160 THEY MUST BE MANAGED IN 2111 01:16:56,160 --> 01:16:56,600 MULTIDISCIPLINARY 2112 01:16:56,600 --> 01:16:58,440 PATIENT-CENTERED APPROACH. 2113 01:16:58,440 --> 01:17:00,720 REALLY OPTIMIZING THEM IN 2114 01:17:00,720 --> 01:17:03,320 CONCERT WITH ONCOLOGY, MEDICINE, 2115 01:17:03,320 --> 01:17:05,080 OBVIOUSLY PT AND OT. 2116 01:17:05,080 --> 01:17:10,440 AND IT'S IMPORTANT TO ENROLL 2117 01:17:10,440 --> 01:17:11,400 THESE PATIENTS IN POSSIBLE 2118 01:17:11,400 --> 01:17:12,520 RESEARCH STUDY, WE HAVE MANY 2119 01:17:12,520 --> 01:17:14,240 MORE QUESTIONS THAN WE HAVE 2120 01:17:14,240 --> 01:17:21,680 ANSWERS, AND REALLY THIS IS THE 2121 01:17:21,680 --> 01:17:22,880 MODEL OF THE LE&RN CENTER OF 2122 01:17:22,880 --> 01:17:23,640 EXCELLENCE OF WHICH WE'RE A 2123 01:17:23,640 --> 01:17:24,000 PART. 2124 01:17:24,000 --> 01:17:25,800 SO IN TERMS OF SURGICAL 2125 01:17:25,800 --> 01:17:31,520 TREATMENTS, IT'S IMPORTANT TO 2126 01:17:31,520 --> 01:17:32,840 UNDERSTAND THE PROCESS OF 2127 01:17:32,840 --> 01:17:34,360 LYMPHEDEMA, STARTING AS A 2128 01:17:34,360 --> 01:17:37,520 CONDITION OF LYMPHATIC FLUID 2129 01:17:37,520 --> 01:17:39,280 STASIS, THEN PHASE IN 2130 01:17:39,280 --> 01:17:41,320 INFLAMMATION, MY BRO CYST AND 2131 01:17:41,320 --> 01:17:47,040 FINALLY ADD ADIPOSE TISSUE 2132 01:17:47,040 --> 01:17:47,480 DIFFERENTIATION. 2133 01:17:47,480 --> 01:17:49,760 SO THEN WE CAN CONSTRUCT AN 2134 01:17:49,760 --> 01:17:50,560 EVIDENCE-BASED TREATMENT 2135 01:17:50,560 --> 01:17:52,840 ALGORITHM BASED OFF PUBLISHED 2136 01:17:52,840 --> 01:17:55,880 STUDIES, WHEREBY EARLY STAGE 2137 01:17:55,880 --> 01:18:00,360 LYMPHEDEMA, ARE THESE PATIENTS 2138 01:18:00,360 --> 01:18:02,360 CANDIDATES FOR BYPASS FROM AREAS 2139 01:18:02,360 --> 01:18:05,280 WHERE THE FLUID IS DEPOSITING 2140 01:18:05,280 --> 01:18:10,120 INTO ADJACENT VENULES. 2141 01:18:10,120 --> 01:18:11,880 THIS IS A MICRO SURGICAL 2142 01:18:11,880 --> 01:18:15,120 PROCEDURE INTRODUCING NEW 2143 01:18:15,120 --> 01:18:16,320 LYMPHATIC FUNCTION IN THE 2144 01:18:16,320 --> 01:18:17,960 AFFECTED EXTREMITY FROM LYMPH 2145 01:18:17,960 --> 01:18:23,640 NODES WHERE THEY CAN BE SPARED 2146 01:18:23,640 --> 01:18:25,600 AND ADVANCED STAGE PATIENTS WILL 2147 01:18:25,600 --> 01:18:26,720 REQUIRE DEBULK WILLING 2148 01:18:26,720 --> 01:18:29,240 PROCEDURES, AND THEN LATE STAGE, 2149 01:18:29,240 --> 01:18:33,040 THEY MAY BE CANDIDATES FOR 2150 01:18:33,040 --> 01:18:33,600 TRANSPLANT PROCEDURE. 2151 01:18:33,600 --> 01:18:35,680 SO WE NOW HAVE MANY VASCULARIZED 2152 01:18:35,680 --> 01:18:36,880 LYMPH NODE TRANSPLANT OPTIONS 2153 01:18:36,880 --> 01:18:39,040 AVAILABLE. 2154 01:18:39,040 --> 01:18:43,080 AND UNFORTUNATELY THERE'S NO 2155 01:18:43,080 --> 01:18:44,640 OPTIONAL TRANSPLANT SO IT ALWAYS 2156 01:18:44,640 --> 01:18:45,800 CAREFUL CONSIDERATION OF THE 2157 01:18:45,800 --> 01:18:46,680 ADVANTAGES AND DISADVANTAGES AND 2158 01:18:46,680 --> 01:18:49,320 ALSO CONSIDERING THE RELATIVE 2159 01:18:49,320 --> 01:18:52,160 REQUIREMENTS OF THE RECIPIENT 2160 01:18:52,160 --> 01:18:53,520 AND THE PATIENT BODY HABITUS AND 2161 01:18:53,520 --> 01:18:55,040 WHAT THEY HAVE AVAILABLE BASED 2162 01:18:55,040 --> 01:18:58,320 ON PREVIOUS SURGERIES. 2163 01:18:58,320 --> 01:18:59,760 JUST AS IN PREHABL TAITION, IT 2164 01:18:59,760 --> 01:19:10,320 IS EQUALLY IMPORTANT PATIENTS -- 2165 01:19:13,040 --> 01:19:14,920 FOR PROXIMAL TRANSPLANTATION 2166 01:19:14,920 --> 01:19:16,680 INTO THE GROIN OR THE AXILLA, 2167 01:19:16,680 --> 01:19:22,920 THAT WILL BE TWO WEEKS 2168 01:19:22,920 --> 01:19:25,960 FOLLOWING -- FOREARM, THEY 2169 01:19:25,960 --> 01:19:27,280 REQUIRE FOUR WEEKS, AND THEN 2170 01:19:27,280 --> 01:19:35,280 THEY GET BACK INTO THEIR -- WE 2171 01:19:35,280 --> 01:19:37,800 TAKE PATIENTS OUT OF THEIR 2172 01:19:37,800 --> 01:19:39,880 GARMENTS AND MEASURE THEM. 2173 01:19:39,880 --> 01:19:40,960 IT'S IMPORTANT AGAIN THAT 2174 01:19:40,960 --> 01:19:41,840 PATIENTS MAINTAIN STABLE WEIGHT. 2175 01:19:41,840 --> 01:19:45,120 THIS CAN BE A COMMON CAUSE OF 2176 01:19:45,120 --> 01:19:45,640 REBOUND. 2177 01:19:45,640 --> 01:19:49,080 AND SO WE LOOKED AT A 2178 01:19:49,080 --> 01:19:51,880 PROSPECTIVE SINGLE SURGEON 2179 01:19:51,880 --> 01:19:55,920 SERIES THAT WAS INDEPENDENTLY 2180 01:19:55,920 --> 01:20:01,080 ANALYZED OF PRIMARY AND 2181 01:20:01,080 --> 01:20:01,760 SECONDARY LYMPHEDEMA PATIENTS, 2182 01:20:01,760 --> 01:20:06,560 THEY UNDERWENT -- PATIENTS THAT 2183 01:20:06,560 --> 01:20:10,920 UNDERWENT LIPECTOMY WERE 2184 01:20:10,920 --> 01:20:11,600 EXCLUDED. 2185 01:20:11,600 --> 01:20:15,920 THE VOLUME OF THE EXTREMITY. 2186 01:20:15,920 --> 01:20:18,640 WE MEASURED THEM AT STANDARDIZED 2187 01:20:18,640 --> 01:20:20,280 PERIOD POSTOPERATIVELY, LOOKING 2188 01:20:20,280 --> 01:20:26,640 AT LYMPH VOLUME CHANGE USING 2189 01:20:26,640 --> 01:20:27,080 PROMETER. 2190 01:20:27,080 --> 01:20:29,720 FOR MAJORITY OF THE PATIENTS THE 2191 01:20:29,720 --> 01:20:31,720 SOZO AND WE ALSO MEASURED 2192 01:20:31,720 --> 01:20:32,640 PATIENT-REPORTED OUTCOME 2193 01:20:32,640 --> 01:20:35,560 MEASURES USING THE LLIS AND ALSO 2194 01:20:35,560 --> 01:20:37,440 MEASURES OF PATIENT-REPORTED 2195 01:20:37,440 --> 01:20:40,720 FUNCTIONAL OUTCOMES, USING THE 2196 01:20:40,720 --> 01:20:42,600 QUICK DASH AND THE LEFS AS 2197 01:20:42,600 --> 01:20:43,240 APPROPRIATE. 2198 01:20:43,240 --> 01:20:46,400 THERE WERE 134 PATIENTS. 2199 01:20:46,400 --> 01:20:48,840 OF NOTE, ALMOST HALF OF THEM HAD 2200 01:20:48,840 --> 01:20:50,600 A BMI OF OVER 30 BUT THAT IS 2201 01:20:50,600 --> 01:20:52,080 TYPICALLY OUR PATIENT POPULATION 2202 01:20:52,080 --> 01:20:53,000 IN TEXAS. 2203 01:20:53,000 --> 01:20:55,080 THE MAJORITY HAD SECONDARY 2204 01:20:55,080 --> 01:20:56,920 LYMPHEDEMA. 2205 01:20:56,920 --> 01:21:04,560 AND 35% HAD A HISTORY OF EPISODE 2206 01:21:04,560 --> 01:21:10,520 OF CELLULITIS. 2207 01:21:10,520 --> 01:21:12,720 THE PREDOMINANTLY PATIENTS WHO 2208 01:21:12,720 --> 01:21:15,520 ARE GETTING GROIN LYMPH NODE 2209 01:21:15,520 --> 01:21:17,360 TRANSPLANTATION, TYPICALLY THIS 2210 01:21:17,360 --> 01:21:19,560 WAS PART OF ABDOMINAL FLAP 2211 01:21:19,560 --> 01:21:20,320 RECONSTRUCTION ALTHOUGH AS YOU 2212 01:21:20,320 --> 01:21:22,080 CAN SEE THE NUMBERS WERE FAIRLY 2213 01:21:22,080 --> 01:21:22,840 OTHERWISE SIMILAR. 2214 01:21:22,840 --> 01:21:24,840 BUT NOTE THAT OVER HALF OF THE 2215 01:21:24,840 --> 01:21:29,400 PATIENTS ALSO GOT SYNCHRONOUS 2216 01:21:29,400 --> 01:21:30,600 LYMPHOVENOUS BYPASS WHICH IS 2217 01:21:30,600 --> 01:21:31,480 TYPICAL IN OUR PATIENT 2218 01:21:31,480 --> 01:21:33,120 POPULATION AND I'M HAPPY TO TALK 2219 01:21:33,120 --> 01:21:37,040 ABOUT LATER ON. 2220 01:21:37,040 --> 01:21:43,160 AND THE OUTCOMES WE SAW VARIOUS 2221 01:21:43,160 --> 01:21:44,480 REDUCTIONS IN -- THROUGH 24 2222 01:21:44,480 --> 01:21:48,200 MONTHS. 2223 01:21:48,200 --> 01:21:49,320 AND THE DATA OVERALL 2224 01:21:49,320 --> 01:21:51,880 DEMONSTRATES THAT THE OUTCOMES 2225 01:21:51,880 --> 01:21:54,640 FROM THE VASCULARIZED LYMPH NODE 2226 01:21:54,640 --> 01:21:55,640 TRANSPLANTS WERE SIMILAR. 2227 01:21:55,640 --> 01:21:58,200 I THINK THAT AS WE COLLECT MORE 2228 01:21:58,200 --> 01:21:59,400 LONG TERM DATA, WE WILL START TO 2229 01:21:59,400 --> 01:22:01,040 NOTICE A BIT MORE OF A 2230 01:22:01,040 --> 01:22:02,480 DIFFERENCE BETWEEN THESE 2231 01:22:02,480 --> 01:22:05,680 DIFFERENT TRANSPLANTATION 2232 01:22:05,680 --> 01:22:05,920 OPTIONS. 2233 01:22:05,920 --> 01:22:07,680 AND WE NOTED THAT OUTCOMES WERE 2234 01:22:07,680 --> 01:22:09,720 BETTER FOR THE OPPORTUNITY IN 2235 01:22:09,720 --> 01:22:11,120 THE LOWER EXTREMITY AND THIS IS 2236 01:22:11,120 --> 01:22:14,160 TYPICALLY BECAUSE THE LOWER 2237 01:22:14,160 --> 01:22:15,160 EXTREMITY IS A SIGNIFICANT 2238 01:22:15,160 --> 01:22:20,120 COMPONENT OF VENOUS 2239 01:22:20,120 --> 01:22:20,960 INSUFFICIENCY -- WHEN WE LOOKED 2240 01:22:20,960 --> 01:22:22,800 AT COMPLICATIONS, THE 2241 01:22:22,800 --> 01:22:24,800 COMPLICATION RATE WAS LOW, THERE 2242 01:22:24,800 --> 01:22:29,440 WERE NO FLAP LOSSES AND -- OF 2243 01:22:29,440 --> 01:22:31,640 THE DONOR EXTREMITY WHERE THE 2244 01:22:31,640 --> 01:22:34,040 LYMPH NODES -- BASIN. 2245 01:22:34,040 --> 01:22:36,160 AND SO 24 MONTHS POSTOPERATIVELY 2246 01:22:36,160 --> 01:22:38,320 WE FOUND MINIMAL CLINICALLY 2247 01:22:38,320 --> 01:22:40,080 IMPORTANT DIFFERENCES FOR LIMB 2248 01:22:40,080 --> 01:22:44,160 VOLUME CHANGE, AN LDEX SCORE IN 2249 01:22:44,160 --> 01:22:47,880 91% OF PATIENTS, PERHAPS MOST 2250 01:22:47,880 --> 01:22:49,320 SIGNIFICANTLY REDUCTION OF 2251 01:22:49,320 --> 01:22:51,280 CELLULITIS BY 98%, PERHAPS THE 2252 01:22:51,280 --> 01:22:55,520 MOST EXCITING PARTS OF THIS 2253 01:22:55,520 --> 01:22:56,320 STUDY, AND THIS HAS BEEN FOUND 2254 01:22:56,320 --> 01:22:58,040 BY OTHER GROUPS AS WELL. 2255 01:22:58,040 --> 01:22:59,480 THE OUTCOMES I MENTIONED WERE 2256 01:22:59,480 --> 01:23:01,320 SIMILAR BETWEEN THE DIFFERENT 2257 01:23:01,320 --> 01:23:02,080 LYMPH NODE FLAPS. 2258 01:23:02,080 --> 01:23:04,960 AND WHEN WE LOOKED AT 2259 01:23:04,960 --> 01:23:06,360 COMPRESSION THERAPY, WE HAVE 2260 01:23:06,360 --> 01:23:08,760 EXTREMELY STRICT CRITERIA FOR 2261 01:23:08,760 --> 01:23:09,800 REMOVING PATIENTS FROM 2262 01:23:09,800 --> 01:23:10,880 COMPRESSION, SO OUR NUMBERS MAY 2263 01:23:10,880 --> 01:23:12,160 BE SLIGHTLY LOWER THAN OTHER 2264 01:23:12,160 --> 01:23:14,760 GROUPS BUT WE FOUND THAT 63% HAD 2265 01:23:14,760 --> 01:23:16,640 EITHER DISCONTINUED OR 2266 01:23:16,640 --> 01:23:17,720 SIGNIFICANTLY REDUCED THEIR USE 2267 01:23:17,720 --> 01:23:20,560 OF COMPRESSION GARMENTS AT A 2268 01:23:20,560 --> 01:23:22,120 MEAN OF A YEAR POSTOPERATIVELY. 2269 01:23:22,120 --> 01:23:23,880 WE HAVE SIGNIFICANT KNOWLEDGE 2270 01:23:23,880 --> 01:23:25,720 GAPS, WHICH WE ARE AIMING TO 2271 01:23:25,720 --> 01:23:26,160 ANSWER. 2272 01:23:26,160 --> 01:23:29,200 WE NEED LONGER TERM OUTCOMES. 2273 01:23:29,200 --> 01:23:32,720 MY EXPERIENCE SINCE DOING THIS 2274 01:23:32,720 --> 01:23:34,160 STUDY AND FROM OTHER DATA THAT'S 2275 01:23:34,160 --> 01:23:35,680 COMING OUT FROM OTHER 2276 01:23:35,680 --> 01:23:36,440 INSTITUTIONS SEEMS TO SHOW THERE 2277 01:23:36,440 --> 01:23:38,840 IS A LONG-TERM STABILITY TO THE 2278 01:23:38,840 --> 01:23:40,840 OUTCOME, AND CERTAINLY WE SEE A 2279 01:23:40,840 --> 01:23:43,120 PROGRESSIVE IMPROVEMENT 2280 01:23:43,120 --> 01:23:44,880 THROUGHOUT -- CAN BE OFTEN 2281 01:23:44,880 --> 01:23:47,080 SEVERAL YEARS SINCE THE SURGERY, 2282 01:23:47,080 --> 01:23:49,840 AND BUT WE NEED TO PROPERLY 2283 01:23:49,840 --> 01:23:51,120 EVALUATE THAT. 2284 01:23:51,120 --> 01:23:53,960 WE ALSO NEED TO DETERMINE WHICH 2285 01:23:53,960 --> 01:23:55,600 PATIENTS BENEFIT FROM 2286 01:23:55,600 --> 01:23:56,800 VASCULARIZED TRANSPLANTATION 2287 01:23:56,800 --> 01:23:57,760 BECAUSE CLEARLY SOME DON'T. 2288 01:23:57,760 --> 01:24:05,800 THERE ARE SOME THAT SEEM TO BE 2289 01:24:05,800 --> 01:24:07,080 HIGHLY SIGNIFICANT INFLAMMATORY 2290 01:24:07,080 --> 01:24:07,760 COMPONENTS TO THEIR LYMPHEDEMA 2291 01:24:07,760 --> 01:24:09,200 AND THEY APPEAR TO BE DIFFICULT 2292 01:24:09,200 --> 01:24:13,760 TO TREAT WITH TRANSPLANTATION. 2293 01:24:13,760 --> 01:24:15,760 WE ALSO NEED LARGE SCALE 2294 01:24:15,760 --> 01:24:17,400 PROSPECTIVE TRIALS TO DETERMINE 2295 01:24:17,400 --> 01:24:18,680 THE OPTIMAL TREATMENT 2296 01:24:18,680 --> 01:24:19,520 ALGORITHMS, WHETHER WE SHOULD BE 2297 01:24:19,520 --> 01:24:23,720 DEBULK WILLING PATIENTS 2298 01:24:23,720 --> 01:24:25,280 DEBULKING OR PERFORMING SURGERY 2299 01:24:25,280 --> 01:24:28,480 FIRST AND DEBULK WILLING THEMBU. 2300 01:24:28,480 --> 01:24:29,920 ALSO AS WE ARE STUDYING THROUGH 2301 01:24:29,920 --> 01:24:31,560 A FUNDED GRANT CURRENTLY, I KNOW 2302 01:24:31,560 --> 01:24:35,400 OTHERS ARE LOOKING AT THIS AS 2303 01:24:35,400 --> 01:24:37,120 WELL, WE NEED TO STATE THE 2304 01:24:37,120 --> 01:24:40,400 MECHANISMS OF OF IMMUNOMODULAN 2305 01:24:40,400 --> 01:24:41,800 FOLLOWING THESE SURGERIES 2306 01:24:41,800 --> 01:24:44,120 BECAUSE THERE'S A REALLY 2307 01:24:44,120 --> 01:24:44,680 FASCINATING IMMUNOMODULATION 2308 01:24:44,680 --> 01:24:45,680 COMPONENT TO THESE SURGERIES AND 2309 01:24:45,680 --> 01:24:51,120 THROUGH THIS WILL AID IN OUR 2310 01:24:51,120 --> 01:24:54,960 DEVELOPMENT TO -- 2311 01:24:54,960 --> 01:24:55,360 PHARMACOTHERAPIES. 2312 01:24:55,360 --> 01:24:56,520 WITH THAT, THANK YOU AND I LOOK 2313 01:24:56,520 --> 01:24:57,440 FORWARD TO ANY QUESTIONS. 2314 01:24:57,440 --> 01:24:59,280 >> THANK YOU, MARC, FOR YOUR 2315 01:24:59,280 --> 01:25:00,560 BEAUTIFUL PRESENTATION. 2316 01:25:00,560 --> 01:25:01,680 WE'LL TAKE QUESTIONS FOR YOU 2317 01:25:01,680 --> 01:25:03,400 ALSO AT THE END OF THE ENTIRE 2318 01:25:03,400 --> 01:25:03,760 SESSION. 2319 01:25:03,760 --> 01:25:07,360 SO IT NOW MY PLEASURE TO 2320 01:25:07,360 --> 01:25:08,360 INTRODUCE RACHELLE CRESCENZI. 2321 01:25:08,360 --> 01:25:10,120 RACHELLE, IF YOU CAN START 2322 01:25:10,120 --> 01:25:14,600 PULLING UP YOUR SLIDES. 2323 01:25:14,600 --> 01:25:15,480 RACHELLE HAS A LITTLE BIT OF 2324 01:25:15,480 --> 01:25:16,600 CHANGE OF TOPIC BECAUSE WE'VE 2325 01:25:16,600 --> 01:25:19,080 BEEN TALKING ABOUT TREATMENT OF 2326 01:25:19,080 --> 01:25:20,960 LYMPHEDEMA, NOW ONE OF THE MAIN 2327 01:25:20,960 --> 01:25:22,080 COMPLAINTS FOR PATIENTS WITH 2328 01:25:22,080 --> 01:25:32,120 LYMPHEDEMA HAS ALSO BEEN AND 2329 01:25:32,120 --> 01:25:33,320 LIPEDEMA -- WE LOOK FORWARD TO 2330 01:25:33,320 --> 01:25:34,400 HER TALK. 2331 01:25:34,400 --> 01:25:35,640 RACHELLE IS AT VANDERBILT 2332 01:25:35,640 --> 01:25:38,560 UNIVERSITY AND HER TITLE IS 2333 01:25:38,560 --> 01:25:39,880 TRANSLATIONAL IMAGING OF SODIUM 2334 01:25:39,880 --> 01:25:43,480 AND ADIPOSE TISSUE IN LYMPHEDEMA 2335 01:25:43,480 --> 01:25:44,000 AND LIPEDEMA. 2336 01:25:44,000 --> 01:25:44,800 SO THE FLOOR IS YOURS. 2337 01:25:44,800 --> 01:25:46,600 >> THANK YOU SO MUCH FOR THE 2338 01:25:46,600 --> 01:25:47,360 OPPORTUNITY TO SPEAK TODAY. 2339 01:25:47,360 --> 01:25:49,800 I WILL BE TALKING ABOUT 2340 01:25:49,800 --> 01:25:50,640 TRANSLATIONAL IMAGING IN 2341 01:25:50,640 --> 01:25:54,040 LYMPHEDEMA AND LIPEDEMA. 2342 01:25:54,040 --> 01:25:55,520 IN THE FIRST PART OF MY TALK 2343 01:25:55,520 --> 01:25:56,360 I'LL SHARE ABOUT SOME 2344 01:25:56,360 --> 01:25:58,520 DEVELOPMENTS IN NONINVASIVE 2345 01:25:58,520 --> 01:25:59,960 IMPANELING OF LYMPHATIC 2346 01:25:59,960 --> 01:26:01,080 PHYSIOLOGY AND WHAT THES CAN 2347 01:26:01,080 --> 01:26:03,680 TELL US ABOUT LYMPHEDEMA AND 2348 01:26:03,680 --> 01:26:05,200 LIPEDEMA AND I'LL FINISH UP WITH 2349 01:26:05,200 --> 01:26:06,440 SOME GAPS AND OPPORTUNITIES IN 2350 01:26:06,440 --> 01:26:06,720 THIS SPACE. 2351 01:26:06,720 --> 01:26:08,040 I HAVE NOTHING TO DISCLOSE OTHER 2352 01:26:08,040 --> 01:26:09,040 THAN THE FACT THAT I'M NOT A 2353 01:26:09,040 --> 01:26:10,480 CLINICIAN SO THE RESEARCH DATA 2354 01:26:10,480 --> 01:26:11,920 PRESENTED IS NOT INTENDED TO 2355 01:26:11,920 --> 01:26:12,960 INFORM AN INDIVIDUAL'S MEDICAL 2356 01:26:12,960 --> 01:26:13,880 CARE. 2357 01:26:13,880 --> 01:26:15,520 SO TODAY WE'LL BE TALKING ABOUT 2358 01:26:15,520 --> 01:26:17,040 SODIUM IN THE BODY. 2359 01:26:17,040 --> 01:26:18,480 WHILE WE THINK ABOUT SODIUM, WE 2360 01:26:18,480 --> 01:26:20,120 TEND TO THINK ABOUT OUR DIETARY 2361 01:26:20,120 --> 01:26:22,320 SODIUM INTAKE AND OUR URINE 2362 01:26:22,320 --> 01:26:23,520 EXCRETION OF SODIUM, BUT IT'S IN 2363 01:26:23,520 --> 01:26:27,040 BETWEEN THAT THERE ARE ME CAN 2364 01:26:27,040 --> 01:26:28,360 MECHANISMS IN THE CIRCULATION 2365 01:26:28,360 --> 01:26:29,560 AND RENAL FILTRATION THAT CAN 2366 01:26:29,560 --> 01:26:31,000 IMPACT SODIUM HANDLING IN THE 2367 01:26:31,000 --> 01:26:32,960 BODY AND TODAY WE'RE GOING TO 2368 01:26:32,960 --> 01:26:34,680 FOCUS ON LYMPHATIC CIRCULATORY 2369 01:26:34,680 --> 01:26:36,040 SYSTEMS THAT CAN MANIFEST IN 2370 01:26:36,040 --> 01:26:37,120 SODIUM TISSUE STORAGE. 2371 01:26:37,120 --> 01:26:38,320 SO SPECIFICALLY IN THE SKIP, 2372 01:26:38,320 --> 01:26:39,640 THESE ARE JUST SOME OF THE 2373 01:26:39,640 --> 01:26:40,960 MARKERS THAT PARTICIPATE IN 2374 01:26:40,960 --> 01:26:42,160 SODIUM HANDLING. 2375 01:26:42,160 --> 01:26:45,120 FOR INSTANCE, SODIUM CAN BIND TO 2376 01:26:45,120 --> 01:26:48,960 NEGATIVELY CHARGED SPECIES LIKE 2377 01:26:48,960 --> 01:26:52,160 GA AGs AND IS ALSO PARTLY 2378 01:26:52,160 --> 01:26:53,800 CLEARED THROUGH THE LYMPHATICS. 2379 01:26:53,800 --> 01:26:55,320 WHAT WE KNOW ABOUT LYMPHATIC 2380 01:26:55,320 --> 01:26:56,080 CLEARANCE OF SODIUM AND OTHER 2381 01:26:56,080 --> 01:26:58,040 MACRO MOLECULES PRIMARILY COMES 2382 01:26:58,040 --> 01:26:59,920 FROM PRE-CLINICAL STUDIES AND 2383 01:26:59,920 --> 01:27:00,880 ANIMAL MODEL SYSTEMS. 2384 01:27:00,880 --> 01:27:03,200 I'M SHOWING AN EXAMPLE HERE OF A 2385 01:27:03,200 --> 01:27:05,960 3D RENDERING OF LYMPHATIC 2386 01:27:05,960 --> 01:27:07,080 VESSELS IN THE MOUSE SKIN AND 2387 01:27:07,080 --> 01:27:09,240 THIS IS COMPARED TO LYMPHATIC 2388 01:27:09,240 --> 01:27:10,440 VESSELS VIEWED IN SKIN WITH HIGH 2389 01:27:10,440 --> 01:27:10,880 SODIUM. 2390 01:27:10,880 --> 01:27:13,120 YOU CAN SEE IN THIS CASE THE 2391 01:27:13,120 --> 01:27:14,200 VESSELS ARE DILATED, THERE'S 2392 01:27:14,200 --> 01:27:15,600 MORE OF THEM, THERE'S MORE 2393 01:27:15,600 --> 01:27:18,920 BRANCHING, AND SO THIS STUDY 2394 01:27:18,920 --> 01:27:21,120 REALLY SHOWED LYMPHATIC VESSELS 2395 01:27:21,120 --> 01:27:23,040 GROW IN RESPONSE TO A HIGH 2396 01:27:23,040 --> 01:27:24,040 SODIUM DIET. 2397 01:27:24,040 --> 01:27:27,440 THIS GROUP ALSO WENT ON TO SHOW 2398 01:27:27,440 --> 01:27:28,200 LYMPHATIC FUNCTION IS ESSENTIAL 2399 01:27:28,200 --> 01:27:29,760 TO CLEAR SODIUM FROM TISSUE AND 2400 01:27:29,760 --> 01:27:31,040 WE ALSO KNOW LYMPHATICS 2401 01:27:31,040 --> 01:27:34,160 TRANSPORT AND METABOLIZE 2402 01:27:34,160 --> 01:27:36,320 LIPOPROTEINS AND FATTY ACIDS IN 2403 01:27:36,320 --> 01:27:37,960 LARGE MACRO MOLECULES. 2404 01:27:37,960 --> 01:27:40,600 THERE'S STILL A QUESTION WHETHER 2405 01:27:40,600 --> 01:27:41,480 THIS PHYSIOLOGY HAS RELEVANCE TO 2406 01:27:41,480 --> 01:27:43,120 THE HUMAN CONDITION AND HOW IT 2407 01:27:43,120 --> 01:27:44,320 CAN IMPACT PATIENTS WITH 2408 01:27:44,320 --> 01:27:44,760 LYMPHATIC DISEASES. 2409 01:27:44,760 --> 01:27:47,200 SO FOR THAT, WE REALLY NEED SOME 2410 01:27:47,200 --> 01:27:48,360 TRANSLATABLE TECHNOLOGIES THAT 2411 01:27:48,360 --> 01:27:49,600 CAN BE APPLIED IN PATIENTS, SO 2412 01:27:49,600 --> 01:27:50,680 OVER THE PAST FEW YEARS, I'VE 2413 01:27:50,680 --> 01:27:52,440 HAD THE PRIVILEGE OF WORKING 2414 01:27:52,440 --> 01:27:55,920 WITH AN AN AMAZING GROUP OF 2415 01:27:55,920 --> 01:27:58,120 SCIENTISTS AND PHYSICIANS AT 2416 01:27:58,120 --> 01:27:59,240 VANDERBILT WHO CARE FOR PATIENTS 2417 01:27:59,240 --> 01:28:00,360 WITH LYMPHATIC DISEASES AND WANT 2418 01:28:00,360 --> 01:28:02,080 TO SEES THESE TECHNOLOGIES IN 2419 01:28:02,080 --> 01:28:04,520 THE CLIN. 2420 01:28:04,520 --> 01:28:04,760 CLINIC. 2421 01:28:04,760 --> 01:28:06,360 IN THE FIRST PART EVER MY TALK 2422 01:28:06,360 --> 01:28:07,800 I'LL GO THROUGH SOME OF THE 2423 01:28:07,800 --> 01:28:09,320 NONINVASIVE METHODS WE'VE BEEN 2424 01:28:09,320 --> 01:28:11,400 WORKING TO DEVELOP IN A WHOLE 2425 01:28:11,400 --> 01:28:12,280 BODY MANNER FOR LYMPHATICS. 2426 01:28:12,280 --> 01:28:13,480 WE FIRST STARTED OUT BY 2427 01:28:13,480 --> 01:28:14,600 MEASURING THE FUNDAMENTAL 2428 01:28:14,600 --> 01:28:17,000 PARAMETERS FOR SETTING IMAGE 2429 01:28:17,000 --> 01:28:19,720 CONTRAST BY MRI IN LYMPH NODES 2430 01:28:19,720 --> 01:28:21,520 THEMSELVES AND VISUALIZING THESE 2431 01:28:21,520 --> 01:28:22,720 STRUCTURES, THEN WE USED THESE 2432 01:28:22,720 --> 01:28:24,880 PARAMETERS TO MOTIVATE AND 2433 01:28:24,880 --> 01:28:28,080 DEVELOP CONTRAST FOR 2434 01:28:28,080 --> 01:28:29,280 NON-TRASER-BASED MR LYMPH 2435 01:28:29,280 --> 01:28:29,760 ANGIOGRAPHY. 2436 01:28:29,760 --> 01:28:32,120 THIS IS SHOWN IN THE UPPER TORSO 2437 01:28:32,120 --> 01:28:34,120 IN AN EXAMPLE OF A PATIENT WITH 2438 01:28:34,120 --> 01:28:35,760 BREAST CANCER LYMPHEDEMA, THEY 2439 01:28:35,760 --> 01:28:36,280 HAD UNILATERAL LYMPHEDEMA. 2440 01:28:36,280 --> 01:28:39,640 YOU CAN SEE THE IMAGE CONTRAST 2441 01:28:39,640 --> 01:28:40,440 HAS HYPERINTENSITIES WHERE 2442 01:28:40,440 --> 01:28:42,120 THERE'S TISSUE EDEMA IN THE 2443 01:28:42,120 --> 01:28:43,000 LATERAL SENSE. 2444 01:28:43,000 --> 01:28:44,720 WE CAN VISUALIZE THE LARGEST 2445 01:28:44,720 --> 01:28:46,720 LYMPHATIC DUCT IN THE BODY HERE 2446 01:28:46,720 --> 01:28:48,120 SHOWING THE THORACIC DUCT. 2447 01:28:48,120 --> 01:28:49,240 THIS METHOD CAN ALSO BE 2448 01:28:49,240 --> 01:28:50,320 TRANSLATED TO THE LOWER 2449 01:28:50,320 --> 01:28:51,680 EXTREMITIES WHERE WE HAVE 2450 01:28:51,680 --> 01:28:55,160 ABILITIES TO MEASURE TISSUE 2451 01:28:55,160 --> 01:28:56,480 COMPOSITION, SO FAT WEIGHTED 2452 01:28:56,480 --> 01:28:58,440 IMAGING AND SODIUM MRI. 2453 01:28:58,440 --> 01:28:59,560 THAT'S WHAT I'LL DESCRIBE NEXT 2454 01:28:59,560 --> 01:29:01,840 IN DETAIL IS SOME OF THESE 2455 01:29:01,840 --> 01:29:02,600 METHODS IN THE LOWER 2456 01:29:02,600 --> 01:29:02,920 EXTREMITIES. 2457 01:29:02,920 --> 01:29:05,040 SO WHEN I -- I WILL PRESENT 2458 01:29:05,040 --> 01:29:07,200 TODAY SEVERAL DATASETS USING 2459 01:29:07,200 --> 01:29:08,880 STANDARDIZED SODIUM MRI AND WHEN 2460 01:29:08,880 --> 01:29:10,640 I SAY STANDARDIZED, I WANT TO BE 2461 01:29:10,640 --> 01:29:11,960 CLEAR WHAT THAT MEANS. 2462 01:29:11,960 --> 01:29:13,920 ALL OF THE SODIUM THAT WE VIZ 2463 01:29:13,920 --> 01:29:16,240 LIESH ON MRI IS NATURALLY 2464 01:29:16,240 --> 01:29:19,920 OCCURRING SODIUM, 20NA. 2465 01:29:19,920 --> 01:29:21,800 WE STANDARDIZED WHERE BELOW THE 2466 01:29:21,800 --> 01:29:23,120 CALF ARE PLACED FOUR SOLUTIONS 2467 01:29:23,120 --> 01:29:25,320 OF STANDARD SALINE WITH KNOWN 2468 01:29:25,320 --> 01:29:26,640 CONCENTRATIONS IN THE 2469 01:29:26,640 --> 01:29:28,840 PHYSIOLOGICAL RANGE, SO FROM 10 2470 01:29:28,840 --> 01:29:34,640 TO 40 MILL EE 40 MILLIMOL. 2471 01:29:34,640 --> 01:29:36,800 SIMILAR CONTRAST ON A WATER 2472 01:29:36,800 --> 01:29:38,480 WEIGHTED CONVENTIONAL MRI. 2473 01:29:38,480 --> 01:29:39,920 WE CALIBRATE EVERY INDIVIDUAL'S 2474 01:29:39,920 --> 01:29:42,240 SKIN AND EACH PIXEL AGAINST 2475 01:29:42,240 --> 01:29:43,320 KNOWN STANDARD SALINE IN ORDER 2476 01:29:43,320 --> 01:29:44,960 TO PRODUCE A QUANTITATIVE AND 2477 01:29:44,960 --> 01:29:46,840 STANDARDIZED TISSUE SODIUM 2478 01:29:46,840 --> 01:29:47,720 CONTENT MAP. 2479 01:29:47,720 --> 01:29:49,800 WE CAN ALSO MEASURE THINGS BY 2480 01:29:49,800 --> 01:29:54,280 IMAGING LIKE ADIPOSE TISSUE 2481 01:29:54,280 --> 01:29:55,160 VOLUME QUANTIFICATION PRETTY 2482 01:29:55,160 --> 01:29:58,240 EASILY. 2483 01:29:58,240 --> 01:29:59,880 YOU CAN IDENTIFY MANUALLY 2484 01:29:59,880 --> 01:30:02,080 REGIONS OF INTEREST ON THESE 2485 01:30:02,080 --> 01:30:03,280 IMAGES, IN OUR CASE WE'RE 2486 01:30:03,280 --> 01:30:04,360 INTERESTED IN THE SKIN, IN THE 2487 01:30:04,360 --> 01:30:07,320 MUSCLE AND THE SUBCUTANEOUS ADD 2488 01:30:07,320 --> 01:30:08,880 TOES TISSUE OR SAT. 2489 01:30:08,880 --> 01:30:11,720 YOU CAN ALSO MEASURE THE VOLUME 2490 01:30:11,720 --> 01:30:12,800 AND TISSUE SODIUM CON AT THE 2491 01:30:12,800 --> 01:30:14,120 PRESENT TIME AND YOU CAN COMBINE 2492 01:30:14,120 --> 01:30:15,680 DIFFERENT VOLUMES TO CREATE A 2493 01:30:15,680 --> 01:30:17,000 METRIC -- ONE OF MY -- THE 2494 01:30:17,000 --> 01:30:17,720 METRICS THAT I USE AND TALK 2495 01:30:17,720 --> 01:30:24,240 ABOUT IS FAT TO WATER VOLUME 2496 01:30:24,240 --> 01:30:24,840 RATIO. 2497 01:30:24,840 --> 01:30:27,320 SO WHAT CAN BECOME INTERESTING 2498 01:30:27,320 --> 01:30:30,080 IS TO PAIR THEM WITH VASCULAR 2499 01:30:30,080 --> 01:30:35,240 IMAGING WITH NONINVASIVE MR 2500 01:30:35,240 --> 01:30:35,760 LYMPHANGIOGRAPHY. 2501 01:30:35,760 --> 01:30:37,240 THIS PATIENT HAS BILATERAL 2502 01:30:37,240 --> 01:30:38,640 LIPEDEMA AND YOU CAN SEE ON THIS 2503 01:30:38,640 --> 01:30:40,280 CONTRAST, WE CAN VISUALIZE LYMPH 2504 01:30:40,280 --> 01:30:41,960 NODE CLUSTERS AND VESSELS GOING 2505 01:30:41,960 --> 01:30:43,160 INTO THE INGUINAL SECTION SHOWN 2506 01:30:43,160 --> 01:30:44,000 IN THE OVAL. 2507 01:30:44,000 --> 01:30:46,200 WE CAN ALSO VISUALIZE 2508 01:30:46,200 --> 01:30:49,960 SUBCUTANEOUS TISSUE LYMPHEDEMA. 2509 01:30:49,960 --> 01:30:50,480 TISSUE EDEMA. 2510 01:30:50,480 --> 01:30:53,560 MOST OCCURS AT THE DISTAL 2511 01:30:53,560 --> 01:30:55,240 EXTREMITIES AT THE LEVEL OF THE 2512 01:30:55,240 --> 01:30:57,400 CALF WHERE SODIUM QUANTIFICATION 2513 01:30:57,400 --> 01:30:58,040 ARE PERFORMED. 2514 01:30:58,040 --> 01:30:59,600 FOR THE NEXT PART OF MY TALK, 2515 01:30:59,600 --> 01:31:01,280 I'LL DESCRIBE HOW THESE IMAGING 2516 01:31:01,280 --> 01:31:02,920 METHODS ARE BEING IMPLIED IN OUR 2517 01:31:02,920 --> 01:31:07,160 STUDIES TO LEG LYMPHEDEMA AND 2518 01:31:07,160 --> 01:31:07,520 LIPEDEMA. 2519 01:31:07,520 --> 01:31:09,000 WE START WITH LEG BECAUSE WE 2520 01:31:09,000 --> 01:31:11,800 KNOW THE SOURCE OF LYMPH INSULT 2521 01:31:11,800 --> 01:31:13,960 DUE TO LYMPH REMOVAL IN THESE 2522 01:31:13,960 --> 01:31:14,840 CANCER CASES. 2523 01:31:14,840 --> 01:31:16,960 WE'VE ALREADY HEARD ABOUT BREAST 2524 01:31:16,960 --> 01:31:18,040 CANCER RELATED LYMPHEDEMA, BUT I 2525 01:31:18,040 --> 01:31:20,000 ALSO WANT TO POINT OUT THAT 2526 01:31:20,000 --> 01:31:21,800 GYNECOLOGICAL CANCER HAS A HIGH 2527 01:31:21,800 --> 01:31:24,080 INCIDENCE, MEANING 27 TO 41% OF 2528 01:31:24,080 --> 01:31:25,960 PATIENTS UNDERGOING TREATMENT 2529 01:31:25,960 --> 01:31:27,240 FOR GYNECOLOGICAL CANCER WILL GO 2530 01:31:27,240 --> 01:31:28,640 ON TO DEVELOP LYMPHEDEMA. 2531 01:31:28,640 --> 01:31:29,680 WHAT'S INTERESTING IS THAT NOT 2532 01:31:29,680 --> 01:31:31,680 ALL OF THESE PATIENTS DEVELOP 2533 01:31:31,680 --> 01:31:32,080 LYMPHEDEMA, RIGHT? 2534 01:31:32,080 --> 01:31:34,280 SO THAT'S WHY WE DO NEED THEE 2535 01:31:34,280 --> 01:31:35,400 PERSONALIZED RISK ASSESSMENT 2536 01:31:35,400 --> 01:31:36,840 MARKERS AND ALSO FOR THOSE 2537 01:31:36,840 --> 01:31:37,800 SUFFERING FROM LYMPHEDEMA LIKE 2538 01:31:37,800 --> 01:31:39,240 OUR PATIENT HERE, WE NEED TO 2539 01:31:39,240 --> 01:31:43,080 DEVELOP TOOLS TO OPTIMIZE THEIR 2540 01:31:43,080 --> 01:31:43,400 THERAPIES. 2541 01:31:43,400 --> 01:31:45,480 IN OUR PRELIMINARY STUDY WE SET 2542 01:31:45,480 --> 01:31:47,360 OUT TO TEST THE HYPOTHESIS THAT 2543 01:31:47,360 --> 01:31:49,360 IN LIMBS WITH LYMPH IMPAIRMENT 2544 01:31:49,360 --> 01:31:51,400 TISSUE SODIUM IS HIGHER COMPARED 2545 01:31:51,400 --> 01:31:52,320 TO CONTRALATERAL LIMBS. 2546 01:31:52,320 --> 01:31:55,640 WE ENROLLED NINE PATIENTS WITH 2547 01:31:55,640 --> 01:31:56,480 CANCER-RELATED LEG LYMPHEDEMA. 2548 01:31:56,480 --> 01:31:57,920 THEY UNDERWENT A PHYSICAL EXAM 2549 01:31:57,920 --> 01:32:00,640 TO CONFIRM THEIR LYMPHEDEMA 2550 01:32:00,640 --> 01:32:03,960 STAGE AND 3T MRI IN ORDER TO 2551 01:32:03,960 --> 01:32:05,120 QUANTIFY AND ANALYZE SODIUM IN 2552 01:32:05,120 --> 01:32:07,040 THE SKIN. 2553 01:32:07,040 --> 01:32:08,480 THE SUBCUTANEOUS ADIPOSE TISSUE 2554 01:32:08,480 --> 01:32:09,440 AND THE MUSCLE. 2555 01:32:09,440 --> 01:32:11,720 AND WHAT I'D LIKE TO DO NEXT IS 2556 01:32:11,720 --> 01:32:16,840 SHOW YOU A FEW CASE EXAMPLES AND 2557 01:32:16,840 --> 01:32:18,560 GROUP RESULTS. 2558 01:32:18,560 --> 01:32:20,200 LOWER EXTREMITY LYMPHEDEMA DUE 2559 01:32:20,200 --> 01:32:22,920 TO CANCER TREATMENT, SEVEN LYMPH 2560 01:32:22,920 --> 01:32:26,200 NODES REMOVED AND SHE'S ACTIVELY 2561 01:32:26,200 --> 01:32:27,640 MANAGED HER LYMPHEDEMA FOR 13 2562 01:32:27,640 --> 01:32:28,200 YEARS. 2563 01:32:28,200 --> 01:32:29,840 THE RIGHT LOWER EXTREMITY IS 2564 01:32:29,840 --> 01:32:31,240 QUITE LARGER THAN THE LEFT AND 2565 01:32:31,240 --> 01:32:33,360 THIS IS THE AFFECTED LEG ON THE 2566 01:32:33,360 --> 01:32:33,680 RIGHT. 2567 01:32:33,680 --> 01:32:35,680 NOW WE'RE GOING TO FOCUS ON THE 2568 01:32:35,680 --> 01:32:37,680 CALF REGION WITH CONVENTIONAL 2569 01:32:37,680 --> 01:32:39,480 MRI, THIS IS WATER-WEIGHTED 2570 01:32:39,480 --> 01:32:40,680 CONTRAST SO BRIGHT REGIONS OF 2571 01:32:40,680 --> 01:32:42,080 THE IMAGE HAVE MORE WATER AND WE 2572 01:32:42,080 --> 01:32:44,680 CAN OBSERVE ON THE AFFECTED 2573 01:32:44,680 --> 01:32:46,200 EXTREMITY THERE'S SKIN 2574 01:32:46,200 --> 01:32:47,640 THICKENING, SEUB CUTANEOUS 2575 01:32:47,640 --> 01:32:50,360 ADIPOSE TISSUE THICKENING AND AN 2576 01:32:50,360 --> 01:32:53,800 AREA OF DENSE TISSUE. 2577 01:32:53,800 --> 01:32:56,400 NEXT WHAT WE SEE ON SODIUM MRI, 2578 01:32:56,400 --> 01:32:58,320 THIS IS AGAIN OUR STANDARDIZED 2579 01:32:58,320 --> 01:33:00,480 IMAGE QUANTIFICATION, SO THIS 2580 01:33:00,480 --> 01:33:01,800 COLORIZED IMAGE WHERE YOU SEE 2581 01:33:01,800 --> 01:33:03,240 YELLOWS AND REDS CORRESPONDS TO 2582 01:33:03,240 --> 01:33:04,680 HIGHER TISSUE SODIUM. 2583 01:33:04,680 --> 01:33:06,760 AND YOU CAN SEE IN THE AFFECTED 2584 01:33:06,760 --> 01:33:08,200 LIMB THERE'S QUITE A BIT MORE 2585 01:33:08,200 --> 01:33:09,520 TISSUE SODIUM AND IT'S ALSO 2586 01:33:09,520 --> 01:33:11,080 LOCALIZED COMPARED TO THE 2587 01:33:11,080 --> 01:33:12,360 CONTRALATERAL LIMB THAT DID NOT 2588 01:33:12,360 --> 01:33:13,480 HAVE LYMPH NODE REMOVAL. 2589 01:33:13,480 --> 01:33:16,440 AND WHAT I LOVE ABOUT THIS CASE 2590 01:33:16,440 --> 01:33:18,200 EXAMPLE IS THE CONTRALATERAL 2591 01:33:18,200 --> 01:33:20,160 LIMB SERVES AS AN EXCELLENT 2592 01:33:20,160 --> 01:33:20,560 INTERNAL CONTROL. 2593 01:33:20,560 --> 01:33:21,920 WE KNOW THESE LEGS DID NOT 2594 01:33:21,920 --> 01:33:23,160 INGEST A DIFFERENT AMOUNT OF 2595 01:33:23,160 --> 01:33:25,000 SODIUM, BUT THE LEG AFFECTED BY 2596 01:33:25,000 --> 01:33:26,680 LYMPHEDEMA STORES MORE SODIUM 2597 01:33:26,680 --> 01:33:28,000 AND THAT'S REALLY WHAT WE MEAN 2598 01:33:28,000 --> 01:33:29,960 BY TISSUE SODIUM STORAGE, AND SO 2599 01:33:29,960 --> 01:33:31,600 WE WANT TO UNDERSTAND WHY THIS 2600 01:33:31,600 --> 01:33:33,240 HAPPENS, HOW IT OCCURS AND 2601 01:33:33,240 --> 01:33:35,120 PROGRESSES, AND WHO MIGHT BE AT 2602 01:33:35,120 --> 01:33:36,480 RISK FOR THIS TYPE OF 2603 01:33:36,480 --> 01:33:38,000 DEVELOPMENT. 2604 01:33:38,000 --> 01:33:40,040 SO NEXT I'LL SHOW TWO MORE CASE 2605 01:33:40,040 --> 01:33:41,040 EXAMPLES BECAUSE THIS ALSO 2606 01:33:41,040 --> 01:33:42,480 APPEARS TO BE STAGE-DEPENDENT. 2607 01:33:42,480 --> 01:33:43,880 SO IN THIS OBSERVATION, THIS IS 2608 01:33:43,880 --> 01:33:49,160 A PATIENT WITH STAGE I 2609 01:33:49,160 --> 01:33:49,640 LYMPHEDEMA. 2610 01:33:49,640 --> 01:33:51,360 ON SODIUM MRI IN THE AFFECTED 2611 01:33:51,360 --> 01:33:53,120 LIMB YOU CAN SEE THERE'S HIGHER 2612 01:33:53,120 --> 01:33:54,920 LEVELS OF THE REDS AND YELLOWS 2613 01:33:54,920 --> 01:33:57,000 SO HIGHER TISSUE SODIUM IN THE 2614 01:33:57,000 --> 01:33:58,200 IMPAIRED LIMB COMPARED TO THE 2615 01:33:58,200 --> 01:34:00,360 CAN TRA LATERAL LIMB WHICH IS IN 2616 01:34:00,360 --> 01:34:05,800 THE DASHED BOX. 2617 01:34:05,800 --> 01:34:08,600 MR LYMPHANGIOGRAPHY SHOWS EDEMA 2618 01:34:08,600 --> 01:34:11,240 IN THE AFFECTED LIMB. 2619 01:34:11,240 --> 01:34:12,280 IN ADVANCED STAGES WE'RE 2620 01:34:12,280 --> 01:34:13,600 STARTING TO OBSERVE AREAS OF 2621 01:34:13,600 --> 01:34:16,240 DENSE TISSUE ABOVE THE -- IN 2622 01:34:16,240 --> 01:34:18,720 MOST CASES ANTERIOR TO THE 2623 01:34:18,720 --> 01:34:20,760 MUSCLE AND THIS HAS RADIOLOGICAL 2624 01:34:20,760 --> 01:34:25,200 EVIDENCE OF FIBROSIS, WHERE WE 2625 01:34:25,200 --> 01:34:27,000 SEE THE HIGHEST AMOUNT OF SODIUM 2626 01:34:27,000 --> 01:34:27,880 DEPOSITION AND ALSO LYMPHEDEMA. 2627 01:34:27,880 --> 01:34:29,160 SO IN THIS PRELIMINARY STUDY, 2628 01:34:29,160 --> 01:34:31,920 SOME OF THE GROUP LEVEL RESULTS 2629 01:34:31,920 --> 01:34:34,080 ARE SHOWING TISSUE SODIUM 2630 01:34:34,080 --> 01:34:35,800 CONTENT IS ELEVATED IN THE SKIN 2631 01:34:35,800 --> 01:34:38,080 AS WELL AS SUBCUTANEOUS ADIPOSE 2632 01:34:38,080 --> 01:34:40,440 TISSUE IN LIMBS WITH LYMPHEDEMA 2633 01:34:40,440 --> 01:34:43,520 COMPARED TO THEIR CONTRALATERAL 2634 01:34:43,520 --> 01:34:45,160 LIMB, STAGE ZERO. 2635 01:34:45,160 --> 01:34:48,800 AND ALSO THAT TISSUE SODIUM 2636 01:34:48,800 --> 01:34:49,880 INCREASES WITH LYMPHEDEMA STAGE. 2637 01:34:49,880 --> 01:34:52,520 THIS EFFORT IS NOW FUNDED BY THE 2638 01:34:52,520 --> 01:34:53,960 NHLBI AND WE'RE PRETTY EXCITED 2639 01:34:53,960 --> 01:34:55,480 TO FOLLOW UP ON THESE 2640 01:34:55,480 --> 01:34:57,480 OBSERVATIONS IN A LARGER COHORT. 2641 01:34:57,480 --> 01:34:58,680 SO WE'RE ALSO INTERESTED IN A 2642 01:34:58,680 --> 01:35:00,560 DISEASE CALLED LIPEDEMA, AND 2643 01:35:00,560 --> 01:35:02,960 THIS IS A DISEASE WITH SUSPECTED 2644 01:35:02,960 --> 01:35:04,880 LYMPHATIC INVOLVEMENT THAT CAN 2645 01:35:04,880 --> 01:35:05,560 APPEAR SIMILAR TO LYMPHEDEMA. 2646 01:35:05,560 --> 01:35:07,720 IT ALSO APPEARS SIMILAR TO 2647 01:35:07,720 --> 01:35:08,760 OBESITY SO I'LL TRY TO WALK YOU 2648 01:35:08,760 --> 01:35:10,120 THROUGH SOME OF THE SYMPTOMS OF 2649 01:35:10,120 --> 01:35:13,520 AND HOW A CLINICIAN WOULD 2650 01:35:13,520 --> 01:35:14,000 DIFFERENTIATE LIPEDEMA. 2651 01:35:14,000 --> 01:35:16,040 SO YOU MIGHT OBSERVE ALL THESE 2652 01:35:16,040 --> 01:35:16,840 PHOTOS ARE FROM PATIENTS WITH 2653 01:35:16,840 --> 01:35:17,800 LIPEDEMA. 2654 01:35:17,800 --> 01:35:18,640 YOU MIGHT OBSERVE THEIR 2655 01:35:18,640 --> 01:35:20,120 EXTREMITIES ARE SWOLLEN AND THIS 2656 01:35:20,120 --> 01:35:22,240 CAN APPEAR SIMILAR TO LYMPHEDEMA 2657 01:35:22,240 --> 01:35:24,480 HOWEVER LIPEDEMA HAS BILATERAL 2658 01:35:24,480 --> 01:35:25,520 LEG SWELLING THAT STOPS AT THE 2659 01:35:25,520 --> 01:35:25,720 FEET. 2660 01:35:25,720 --> 01:35:26,960 SO YOU MIGHT ALSO OBSERVE THE 2661 01:35:26,960 --> 01:35:28,680 BODY CONTOURS ARE 2662 01:35:28,680 --> 01:35:29,600 DISPROPORTIONATE, AND THAT MIGHT 2663 01:35:29,600 --> 01:35:31,840 BE SIMILAR TO OBESITY, HOWEVER, 2664 01:35:31,840 --> 01:35:35,520 LIPEDEMA HAS MORE OF A GYNOID 2665 01:35:35,520 --> 01:35:37,600 FAT DISTRIBUTION AND LEG GIRTH 2666 01:35:37,600 --> 01:35:40,360 IS RESISTANT TO DIET, EXERCISE 2667 01:35:40,360 --> 01:35:41,920 OR BARIATRIC SURGERY AND THAT IS 2668 01:35:41,920 --> 01:35:44,200 DIFFERENT FROM OBESITY. 2669 01:35:44,200 --> 01:35:46,320 LIPEDEMA ALMOST EXCLUSIVELY 2670 01:35:46,320 --> 01:35:49,840 AFFECTS FEMALES, THE FAT IS 2671 01:35:49,840 --> 01:35:51,600 PAINFUL, EASY BRUISING AND 2672 01:35:51,600 --> 01:35:52,840 THERE'S A LOW PREVALENCE OF 2673 01:35:52,840 --> 01:35:54,120 DIABETES OR METABOLIC DISEASE 2674 01:35:54,120 --> 01:35:56,200 DESPITE HAVING HIGH BMI. 2675 01:35:56,200 --> 01:35:58,080 SO WHAT'S NEEDED IN THIS SPACE 2676 01:35:58,080 --> 01:35:59,280 CLINICALLY IS FOR AN OBJECTIVE 2677 01:35:59,280 --> 01:36:00,720 TOOL AND WAY TO DISTINGUISH 2678 01:36:00,720 --> 01:36:01,720 BETWEEN THESE DISEASES BECAUSE 2679 01:36:01,720 --> 01:36:03,600 IT HAS A VERY COMPLEX 2680 01:36:03,600 --> 01:36:07,120 DIFFERENTIAL DIAGNOSIS. 2681 01:36:07,120 --> 01:36:09,000 SO WE THINK IMAGING CAN PLAY A 2682 01:36:09,000 --> 01:36:10,400 PART IN THIS. 2683 01:36:10,400 --> 01:36:12,960 SO HERE'S WHOLE BODY IMAGING IN 2684 01:36:12,960 --> 01:36:14,080 A HEALTHY FEMALE COMPARED TO A 2685 01:36:14,080 --> 01:36:15,920 PATIENT WITH STAGE I LIPEDEMA. 2686 01:36:15,920 --> 01:36:17,480 THEY HAVE SIMILAR B PL. I. 2687 01:36:17,480 --> 01:36:19,120 THIS IS A FAT-WEIGHTED CONTRAST, 2688 01:36:19,120 --> 01:36:20,600 SO IF YOU START TO OBSERVE AT 2689 01:36:20,600 --> 01:36:21,640 THE WAIST YOU MAY SEE THAT THEY 2690 01:36:21,640 --> 01:36:25,240 HAVE A SIMILAR AMOUNT OF FAT 2691 01:36:25,240 --> 01:36:26,440 DEPOSITION BUT AS YOU SCAN DOWN 2692 01:36:26,440 --> 01:36:27,440 THROUGH THE LEGS AND FOLLOW 2693 01:36:27,440 --> 01:36:29,160 THESE ARROWS DOWN, YOU CAN 2694 01:36:29,160 --> 01:36:31,120 OBSERVE THERE'S GREATER FAT 2695 01:36:31,120 --> 01:36:32,600 DEPOSITION SUBCUTANEOUSLY IN THE 2696 01:36:32,600 --> 01:36:33,080 PATIENT WITH LIPEDEMA. 2697 01:36:33,080 --> 01:36:35,280 SO NOW FOCUSING ON THE CALF, I'M 2698 01:36:35,280 --> 01:36:36,720 SHOWING A FAT-WEIGHTED TISSUE 2699 01:36:36,720 --> 01:36:40,800 CONTRAST ON THE TOP IMAGE AND A 2700 01:36:40,800 --> 01:36:41,560 WATER-WEIGHTED ON THE BOTTOM. 2701 01:36:41,560 --> 01:36:42,720 HERE'S WHAT WE START TO OBSERVE 2702 01:36:42,720 --> 01:36:44,000 AND BEGIN TO QUANTIFY, THAT 2703 01:36:44,000 --> 01:36:46,400 THERE'S A FAT TO WATER VOLUME 2704 01:36:46,400 --> 01:36:47,840 RATIO ABOUT A LITTLE GREATER 2705 01:36:47,840 --> 01:36:49,160 THAN 1 OR ABOUT 1 IN THE PATIENT 2706 01:36:49,160 --> 01:36:49,720 WITH LIPEDEMA. 2707 01:36:49,720 --> 01:36:52,160 SO THAT MEANS AS MUCH FAT IS 2708 01:36:52,160 --> 01:36:55,640 SUPPORTED BY THE MUSCLE. 2709 01:36:55,640 --> 01:36:57,720 THIS IS THREE TIMES HIGHER FROM 2710 01:36:57,720 --> 01:36:59,760 A FEMALE WITH SIMILAR BMI. 2711 01:36:59,760 --> 01:37:04,120 HERE'S ANOTHER CASE EXAMPLE OF 2712 01:37:04,120 --> 01:37:05,000 ADVANCED STAGE III LIPEDEMA. 2713 01:37:05,000 --> 01:37:08,400 I'M SHOWING A CONTROL CASE 2714 01:37:08,400 --> 01:37:09,880 AGAINST LIPEDEMA CASE. 2715 01:37:09,880 --> 01:37:12,280 IN THE MIDDLE I'M SHOWING 2716 01:37:12,280 --> 01:37:14,320 FOREARM IMAGING AND ON THE 2717 01:37:14,320 --> 01:37:16,200 RIGHT, CALF LOWER EXTREMITY 2718 01:37:16,200 --> 01:37:16,680 IMAGING. 2719 01:37:16,680 --> 01:37:18,080 WHAT THIS STUDY HAS SHOWN US IS 2720 01:37:18,080 --> 01:37:19,520 THAT THERE'S A SIMILAR AMOUNT OF 2721 01:37:19,520 --> 01:37:21,400 FAT DEPOSITION IN THE UPPER 2722 01:37:21,400 --> 01:37:25,800 EXTREMITIES AS WELL AS SODIUM 2723 01:37:25,800 --> 01:37:29,800 CONTENT IN PATIENTS WITH 2724 01:37:29,800 --> 01:37:30,240 LIPEDEMA. 2725 01:37:30,240 --> 01:37:35,720 IN THE LOWER EXTREMITIES, IT'S 2726 01:37:35,720 --> 01:37:37,200 FULL OF SODIUM IN ALL THE 2727 01:37:37,200 --> 01:37:37,880 COMPARTMENTS WE'RE INTERESTED 2728 01:37:37,880 --> 01:37:38,200 IN. 2729 01:37:38,200 --> 01:37:39,920 SO HOW CAN WE USE THESE METRICS 2730 01:37:39,920 --> 01:37:41,840 TO MAYBE COMPARE AND 2731 01:37:41,840 --> 01:37:42,480 DIFFERENTIATE THESE DISEASES? 2732 01:37:42,480 --> 01:37:45,880 THE GRAPH ON THE LEFT IS SHOWING 2733 01:37:45,880 --> 01:37:49,840 LEG FAT FRACTION OR FAT TO WATER 2734 01:37:49,840 --> 01:37:50,600 RATIO. 2735 01:37:50,600 --> 01:37:55,200 IN THE CONTROL LIPEDEMA AND 2736 01:37:55,200 --> 01:37:58,520 LYMPHEDEMA PATIENTS. 2737 01:37:58,520 --> 01:38:00,480 ELEVATED FAT FRACTION HAS THE 2738 01:38:00,480 --> 01:38:02,240 LARGEST EFFECT SIZE IN LIPEDEMA. 2739 01:38:02,240 --> 01:38:04,320 THE GRAPH ON THE RIDE IS SHOWING 2740 01:38:04,320 --> 01:38:05,760 SKIN SODIUM IN THESE COHORTS. 2741 01:38:05,760 --> 01:38:10,720 WE SEE THE HIGHEST IN LYMPHEDEMA 2742 01:38:10,720 --> 01:38:12,080 BUT THERE'S ALSO A HIGHER AMOUNT 2743 01:38:12,080 --> 01:38:12,920 IN LIPEDEMA. 2744 01:38:12,920 --> 01:38:14,240 SO WE THINK TOGETHER THESE TOOLS 2745 01:38:14,240 --> 01:38:16,240 MIGHT BE USEFUL FOR 2746 01:38:16,240 --> 01:38:17,120 DIFFERENTIATING THESE CONDITIONS 2747 01:38:17,120 --> 01:38:18,640 AND IT ALSO TELLS US SOMETHING 2748 01:38:18,640 --> 01:38:19,520 ABOUT LIPEDEMA BECAUSE IT SHARES 2749 01:38:19,520 --> 01:38:24,160 SOME SIMILAR FEATURES TO LEG 2750 01:38:24,160 --> 01:38:24,480 LYMPHEDEMA. 2751 01:38:24,480 --> 01:38:25,800 SO I JUST WANT TO SHOW THIS 2752 01:38:25,800 --> 01:38:28,680 CONCEPT IN A REPRESENTATIVE CASE 2753 01:38:28,680 --> 01:38:30,160 EXAMPLE FINALLY THAT WHEN WE 2754 01:38:30,160 --> 01:38:31,640 COMBINE THESE IMAGING METHODS 2755 01:38:31,640 --> 01:38:33,040 TOGETHER, THIS MAY BE WHAT'S 2756 01:38:33,040 --> 01:38:34,240 REQUIRED TO REALLY START TO 2757 01:38:34,240 --> 01:38:36,040 PROFILE AND UNDERSTAND HOW 2758 01:38:36,040 --> 01:38:38,680 VASCULAR FUNCTION CAN IMPACT 2759 01:38:38,680 --> 01:38:40,640 TISSUE SODIUM AND FAT 2760 01:38:40,640 --> 01:38:42,080 COMPOSITION AND THERE MIGHT BE 2761 01:38:42,080 --> 01:38:43,600 OTHER METRICS OUT THERE THAT WE 2762 01:38:43,600 --> 01:38:44,280 CAN BEGIN TO LOOK AT. 2763 01:38:44,280 --> 01:38:45,960 BUT I THINK THESE ARE STARTING 2764 01:38:45,960 --> 01:38:47,320 TO SHOW -- THESE CASES ARE 2765 01:38:47,320 --> 01:38:48,520 STARTING TO SHOW SOME REALLY 2766 01:38:48,520 --> 01:38:49,600 INTERESTING THINGS ABOUT 2767 01:38:49,600 --> 01:38:50,920 VASCULAR FUNCTION IN THE LOWER 2768 01:38:50,920 --> 01:38:51,480 EXTREMITIES. 2769 01:38:51,480 --> 01:38:56,120 HERE ON MR LYMPHANGIOGRAPHY YOU 2770 01:38:56,120 --> 01:38:58,520 CAN SEE SORT OF AN INTERMEDIATE 2771 01:38:58,520 --> 01:39:02,680 LEVEL OF TISSUE VASCULARITY 2772 01:39:02,680 --> 01:39:04,200 COMPARED TO -- AND THAT ALSO 2773 01:39:04,200 --> 01:39:05,440 CORRESPONDS TO THEIR SODIUM 2774 01:39:05,440 --> 01:39:10,840 DEPOSITION IN THE LEG. 2775 01:39:10,840 --> 01:39:12,040 IN SUMMARY, THERE'S A CLINICAL 2776 01:39:12,040 --> 01:39:14,240 NEED FOR DEVELOPMENT OF 2777 01:39:14,240 --> 01:39:15,120 NONINVASIVE IMAGING OF LYMPHATIC 2778 01:39:15,120 --> 01:39:16,240 PHYSIOLOGY AND THIS CAN AID THE 2779 01:39:16,240 --> 01:39:18,200 DIAGNOSIS AND UNDERSTANDING OF 2780 01:39:18,200 --> 01:39:19,520 LYMPHEDEMA AND LIPEDEMA. 2781 01:39:19,520 --> 01:39:20,760 MRI TOOLS ARE WHAT I PRESENTED 2782 01:39:20,760 --> 01:39:23,920 TODAY, INCLUDING NONINVASIVE MR 2783 01:39:23,920 --> 01:39:26,120 LYMPHANGIOGRAPHY, ANATOMICAL AND 2784 01:39:26,120 --> 01:39:29,240 SODIUM MRI, AND THESE CAN BE 2785 01:39:29,240 --> 01:39:31,600 PERFORMED IN A CLINICALLY 2786 01:39:31,600 --> 01:39:33,960 FEASIBLE SCAN TIME AT 3 MINUTES 2787 01:39:33,960 --> 01:39:34,400 TOTAL. 2788 01:39:34,400 --> 01:39:36,600 OUR RESEARCH RESULTS WERE 2789 01:39:36,600 --> 01:39:39,000 PRELIMINARY BUT SHOWED US EDEMA 2790 01:39:39,000 --> 01:39:40,560 AND SODIUM ARE PRESENT IN LIMBS 2791 01:39:40,560 --> 01:39:41,880 WITH LYMPHEDEMA. 2792 01:39:41,880 --> 01:39:44,200 PRELIMINARY DATA INDICATES SKIN 2793 01:39:44,200 --> 01:39:45,840 SODIUM INCREASES WITH LYMPHEDEMA 2794 01:39:45,840 --> 01:39:47,960 STAGE AND SKIN AND SUBCUTANEOUS 2795 01:39:47,960 --> 01:39:49,480 ADIPOSE TISSUE AND LIPEDEMA 2796 01:39:49,480 --> 01:39:51,320 CONTAINS HIGH SODIUM CONTENT AND 2797 01:39:51,320 --> 01:39:51,560 EDIE MA. 2798 01:39:51,560 --> 01:39:55,200 IF YOU 2799 01:39:55,200 --> 01:39:55,560 EDEMA. 2800 01:39:55,560 --> 01:39:58,040 YOU CAN FOLLOW OUR LATEST 2801 01:39:58,040 --> 01:39:59,200 PUBLICATION IN JMRI. 2802 01:39:59,200 --> 01:40:02,280 I WANT TO END WITH SOME GAPS IN 2803 01:40:02,280 --> 01:40:03,040 CLINICAL IMAGING. 2804 01:40:03,040 --> 01:40:04,520 I WANT TO HIGHLIGHT THE 2805 01:40:04,520 --> 01:40:05,360 TRANSLATIONAL PATHWAY THAT 2806 01:40:05,360 --> 01:40:11,200 THERE'S A ROLE IN ALL PHASES OF 2807 01:40:11,200 --> 01:40:11,760 SCIENCE. 2808 01:40:11,760 --> 01:40:13,000 THEY NEED SOLUTIONS NOW AND THEY 2809 01:40:13,000 --> 01:40:13,800 NEED SOMETHING THEY CAN GET IN 2810 01:40:13,800 --> 01:40:14,480 THE CLINIC NOW. 2811 01:40:14,480 --> 01:40:15,920 I KNOW THERE'S SOME BEAUTIFUL 2812 01:40:15,920 --> 01:40:17,560 WORK WE CAN ALL DO AND WE CAN 2813 01:40:17,560 --> 01:40:19,040 IMPROVE UPON THE TECHNIQUES AND 2814 01:40:19,040 --> 01:40:20,160 TECHNOLOGIES BUT I THINK WE 2815 01:40:20,160 --> 01:40:21,440 REALLY SHOULD BE LOOKING OUT FOR 2816 01:40:21,440 --> 01:40:22,880 THOSE TECHNIQUES THAT CAN BE 2817 01:40:22,880 --> 01:40:26,680 APPLIED IN THE CLIN CLICK ANE 2818 01:40:26,680 --> 01:40:27,720 LATER PHASES OF TRANSLATION. 2819 01:40:27,720 --> 01:40:30,960 MY STUDY FALLS AROUND T1, MAYBE 2820 01:40:30,960 --> 01:40:32,160 T2, AND I THINK THERE'S SOME 2821 01:40:32,160 --> 01:40:32,880 REALLY EXCITING OPPORTUNITIES 2822 01:40:32,880 --> 01:40:34,160 THAT ARE OUT THERE. 2823 01:40:34,160 --> 01:40:35,800 FOR INSTANCE, THERE'S SOME 2824 01:40:35,800 --> 01:40:36,920 LYMPHATIC THERAPIES THAT ARE 2825 01:40:36,920 --> 01:40:39,320 BEING INVESTIGATED AND WE'VE 2826 01:40:39,320 --> 01:40:40,240 ALREADY HEARD ABOUT SOME OF 2827 01:40:40,240 --> 01:40:41,360 THESE TODAY FROM OUR SURGICAL 2828 01:40:41,360 --> 01:40:41,760 TEAMS. 2829 01:40:41,760 --> 01:40:43,480 IN OUR STUDY, WE'RE EVALUATING 2830 01:40:43,480 --> 01:40:44,400 STANDARD OF CARE PHYSICAL 2831 01:40:44,400 --> 01:40:45,840 THERAPY BECAUSE WE THINK THIS 2832 01:40:45,840 --> 01:40:47,480 CAN HELP DEMONSTRATE AND 2833 01:40:47,480 --> 01:40:49,240 VALIDATE THE NOVEL IMAGING 2834 01:40:49,240 --> 01:40:53,360 METHODS THAT WE'VE BEEN 2835 01:40:53,360 --> 01:40:55,080 OBSERVING IN CROSS-SECTIONAL 2836 01:40:55,080 --> 01:40:55,560 STUDY DESIGNS. 2837 01:40:55,560 --> 01:41:00,080 IN THIS CASE I'M SHOWING LYMPH 2838 01:41:00,080 --> 01:41:03,480 ANGIOCHANGES PRE AND POST -- BUT 2839 01:41:03,480 --> 01:41:07,400 THERE'S ALSO SOME EXCITING FARM 2840 01:41:07,400 --> 01:41:08,720 PHARMACEUTICAL AND SURGICAL 2841 01:41:08,720 --> 01:41:10,240 THERAPIES BEING DEVELOPED FOR 2842 01:41:10,240 --> 01:41:12,160 LYMPHEDEMA AND I THINK 2843 01:41:12,160 --> 01:41:13,760 TECHNOLOGY CAN PLAY A ROLE IN 2844 01:41:13,760 --> 01:41:14,240 EVALUATING THOSE. 2845 01:41:14,240 --> 01:41:16,600 I'D LIKE TO ACKNOWLEDGE MY 2846 01:41:16,600 --> 01:41:19,760 COLLEAGUES AND COLLABORATORS, 2847 01:41:19,760 --> 01:41:21,600 THE AMERICAN HEART ASSOCIATION, 2848 01:41:21,600 --> 01:41:25,800 THE LIPEDEMA FOUNDATION AND THE 2849 01:41:25,800 --> 01:41:26,760 NHI FOR SUPPORTING THIS WORK. 2850 01:41:26,760 --> 01:41:27,920 IF YOU WANT TO WORK WITH US IN 2851 01:41:27,920 --> 01:41:29,440 ANY WAY, PLEASE REACH OUT TO ME 2852 01:41:29,440 --> 01:41:35,000 OR THE LAB BY EMAILING US, 2853 01:41:35,000 --> 01:41:35,840 >> AWESOME. 2854 01:41:35,840 --> 01:41:37,280 THANK YOU, RACHELLE. 2855 01:41:37,280 --> 01:41:38,320 THAT WAS BEAUTIFUL WORK. 2856 01:41:38,320 --> 01:41:40,720 I ALWAYS ENJOY HEARING YOUR 2857 01:41:40,720 --> 01:41:42,120 PROGRESS AS WELL, SO 2858 01:41:42,120 --> 01:41:42,880 CONGRATULATIONS ON THAT. 2859 01:41:42,880 --> 01:41:46,560 SO AGAIN, WE WILL TAKE QUESTIONS 2860 01:41:46,560 --> 01:41:47,880 WITH YOU AND THE GROUP AT THE 2861 01:41:47,880 --> 01:41:50,040 END, SO NOW IT'S MY PLEASURE TO 2862 01:41:50,040 --> 01:41:52,760 INTRODUCE OUR NEXT SPEAKER, MARK 2863 01:41:52,760 --> 01:41:54,560 NICOLLS, WHO IS AT STANFORD 2864 01:41:54,560 --> 01:41:55,160 UNIVERSITY SCHOOL OF MEDICINE 2865 01:41:55,160 --> 01:41:56,320 AND HE'LL BE TALKING TO US ABOUT 2866 01:41:56,320 --> 01:41:57,760 THE PATHWAYS OF INJURY AND 2867 01:41:57,760 --> 01:42:01,680 REPAIR IN LYMPHEDEMA. 2868 01:42:01,680 --> 01:42:02,480 THE FLOOR IS YOURS. 2869 01:42:02,480 --> 01:42:02,880 >> THANK YOU. 2870 01:42:02,880 --> 01:42:09,280 CAN YOU HEAR ME? 2871 01:42:09,280 --> 01:42:10,160 >> YEP, WE CAN HEAR YOU WELL. 2872 01:42:10,160 --> 01:42:10,600 THANK YOU. 2873 01:42:10,600 --> 01:42:11,720 >> THANK YOU VERY MUCH, TIM AND 2874 01:42:11,720 --> 01:42:12,760 THE ORGANIZERS OF THIS 2875 01:42:12,760 --> 01:42:15,560 CONFERENCE. 2876 01:42:15,560 --> 01:42:17,920 SO WHAT I'LL BE TALKING ABOUT 2877 01:42:17,920 --> 01:42:19,200 TODAY IS LYMPHEDEMA AS A 2878 01:42:19,200 --> 01:42:21,160 PARADIGM FOR EVALUATING 2879 01:42:21,160 --> 01:42:23,240 LYMPHATIC DYSFUNCTION. 2880 01:42:23,240 --> 01:42:25,000 AND WE HEARD A PREVIEW OF SOME 2881 01:42:25,000 --> 01:42:27,960 OF THE THINGS I'M GOING TO TALK 2882 01:42:27,960 --> 01:42:29,520 ABOUT TODAY AS DR. ROCKSON GAVE 2883 01:42:29,520 --> 01:42:32,200 IN THE KEYNOTE ADDRESS A TRIAL 2884 01:42:32,200 --> 01:42:41,240 THAT WAS INVOLVING -- TARGETING 2885 01:42:41,240 --> 01:42:43,520 5-LIPOXGENASE IN LYMPHEDEMA AND 2886 01:42:43,520 --> 01:42:44,320 WE'LL RETREAD SOME OF THE GROUND 2887 01:42:44,320 --> 01:42:46,040 THAT DR. ROCKSON TALKED ABOUT 2888 01:42:46,040 --> 01:42:47,840 BUT FLESH OUT SOME OF THE 2889 01:42:47,840 --> 01:42:48,600 SCIENTIFIC DETAILS A LITTLE BIT 2890 01:42:48,600 --> 01:42:48,920 MORE. 2891 01:42:48,920 --> 01:42:51,880 THEN WE'LL GET INTO SOME NEWER 2892 01:42:51,880 --> 01:42:55,440 BIOLOGY ABOUT HOW HIF MIGHT BE 2893 01:42:55,440 --> 01:42:58,960 CONTRIBUTING TO LYMPHATIC REPAIR 2894 01:42:58,960 --> 01:42:59,720 AND LYMPHATIC HEALTH. 2895 01:42:59,720 --> 01:43:01,240 WE'LL ALSO BRIEFLY TALK ABOUT 2896 01:43:01,240 --> 01:43:04,960 NEW RESEARCH NOW BEING PUBLISHED 2897 01:43:04,960 --> 01:43:08,360 ON SPHINGOSINE SIGNALING AND 2898 01:43:08,360 --> 01:43:08,640 LYMPHATICS. 2899 01:43:08,640 --> 01:43:10,960 SO I WAS ASKED TO REALLY TALK 2900 01:43:10,960 --> 01:43:13,800 ABOUT HOW INFLAMMATION MAY BE 2901 01:43:13,800 --> 01:43:17,440 AFFECTING THE EVOLUTION OF 2902 01:43:17,440 --> 01:43:17,960 LYMPHEDEMA. 2903 01:43:17,960 --> 01:43:20,880 WE KNOW THAT WITH THE 2904 01:43:20,880 --> 01:43:22,960 PATHOPHYSIOLOGY OF ACQUIRED 2905 01:43:22,960 --> 01:43:24,280 LYMPHEDEMA, LYMPHATIC INJURY CAN 2906 01:43:24,280 --> 01:43:26,360 BE CAUSED BY SURGERY, RADIATION 2907 01:43:26,360 --> 01:43:28,520 AND OBESITY, AND WE'VE HEARD 2908 01:43:28,520 --> 01:43:31,040 ABOUT SOME OF THOSE FACTORS IN 2909 01:43:31,040 --> 01:43:35,720 THIS SESSION. 2910 01:43:35,720 --> 01:43:41,440 WE KNOW TH1, TH2 AND TH17 ALONG 2911 01:43:41,440 --> 01:43:42,880 WITH ACTIVATED MACROPHAGES AND 2912 01:43:42,880 --> 01:43:44,440 NEUTROPHILS CAN BE PRESENT AND 2913 01:43:44,440 --> 01:43:45,480 LIKELY HARMFUL IN THIS 2914 01:43:45,480 --> 01:43:46,000 CONDITION. 2915 01:43:46,000 --> 01:43:54,160 OUR GROUP HELPED CHARACTERIZE 2916 01:43:54,160 --> 01:43:56,480 LEUKO -- THERE'S ALSO 2917 01:43:56,480 --> 01:43:59,040 INSUFFICIENT REPARATIVE IMMUNE 2918 01:43:59,040 --> 01:44:01,360 RESPONSES WITH T REG ACTIVITY 2919 01:44:01,360 --> 01:44:04,280 AND MACROPHAGES AS WELL AS 2920 01:44:04,280 --> 01:44:05,400 INSUFFICIENT REPARATIVE FACTOR 2921 01:44:05,400 --> 01:44:09,200 PRODUCTION, NOTELY, VEGF C. 2922 01:44:09,200 --> 01:44:10,840 ALL OF THIS RESULTS IN A LOSS OF 2923 01:44:10,840 --> 01:44:12,080 SMOOTH MUSCLE SELL COVERAGE, 2924 01:44:12,080 --> 01:44:14,440 FLUID RETENTION, FIBROSIS, AND 2925 01:44:14,440 --> 01:44:17,720 ADIPOSE DEPOSITION. 2926 01:44:17,720 --> 01:44:20,080 SO I'M NOT GOING TO BELABOR THIS 2927 01:44:20,080 --> 01:44:23,360 STUDY TOO MUCH, WHICH STAN 2928 01:44:23,360 --> 01:44:24,920 DESCRIBED THIS MORNING. 2929 01:44:24,920 --> 01:44:26,640 SUFFICE TO SAY THERE WAS A 2930 01:44:26,640 --> 01:44:28,720 RATIONALE FOR TARGETING 2931 01:44:28,720 --> 01:44:29,840 INFLAMMATION IN LYMPHEDEMA, AND 2932 01:44:29,840 --> 01:44:34,320 THIS LED TO USING KETOPROFEN, 2933 01:44:34,320 --> 01:44:36,720 WHICH IS AN NSAID WITH DUAL 2934 01:44:36,720 --> 01:44:40,080 ANTI-INFLAMMATORY MECHANISM, BUT 2935 01:44:40,080 --> 01:44:41,720 IT HAS SOME UNTOWARD PROPERTIES 2936 01:44:41,720 --> 01:44:43,920 WHICH MAKE US NOT WANT TO USE IT 2937 01:44:43,920 --> 01:44:44,800 CLINICALLY FOR LONG TERM. 2938 01:44:44,800 --> 01:44:55,200 WE KNOW THAT IT INHIBITS 2939 01:44:57,280 --> 01:44:59,400 5-LIPOXYGENASE AND COX2, WE 2940 01:44:59,400 --> 01:45:03,560 DIDN'T REALLY KNOW WHY 2941 01:45:03,560 --> 01:45:05,960 5-LIPOXYGENASE WAS HELPING, WHY 2942 01:45:05,960 --> 01:45:08,480 WE'RE TARGETING 5-LO WOULD BE 2943 01:45:08,480 --> 01:45:10,840 HELPFUL AND IS THAT THE REASON 2944 01:45:10,840 --> 01:45:12,160 WHY KETO WAS WORKING. 2945 01:45:12,160 --> 01:45:16,080 THIS IS A NICE REVEUL THAT JIANG 2946 01:45:16,080 --> 01:45:18,920 IN MY LAB WITH AN R01 FOCUSING 2947 01:45:18,920 --> 01:45:21,960 ON LYMPHEDEMA SHOWS HOW NUCLEAR 2948 01:45:21,960 --> 01:45:24,480 5-LO CAN GET PHOSPHORYLATED 2949 01:45:24,480 --> 01:45:26,640 TRANSIENTLY LEAD TO LTA4 AND 2950 01:45:26,640 --> 01:45:30,360 THEN DEPENDING ON WHERE THE 2951 01:45:30,360 --> 01:45:36,680 ENZYME IS ACTIVATED, CAN EITHER 2952 01:45:36,680 --> 01:45:38,200 GENERATE -- ASSOCIATED WITH 2953 01:45:38,200 --> 01:45:39,640 BRONCHOCONSTRICTION AND A 2954 01:45:39,640 --> 01:45:42,040 VARIETY OF OTHER PARAMETERS AS 2955 01:45:42,040 --> 01:45:45,200 WELL AS LTB4, WHICH CAN BIND TO 2956 01:45:45,200 --> 01:45:48,720 ITS RECEPTORS, MAINLY BLT1, BUT 2957 01:45:48,720 --> 01:45:50,800 ALSO BL T2. 2958 01:45:50,800 --> 01:45:51,760 THIS HAS BEEN ASSOCIATED WITH A 2959 01:45:51,760 --> 01:45:56,480 VARIETY OF CONDITIONS, BUT WHAT 2960 01:45:56,480 --> 01:45:58,200 WE HAD DISCOVERED SEVERAL YEARS 2961 01:45:58,200 --> 01:46:00,160 PRIOR LOOKING AT PULMONARY 2962 01:46:00,160 --> 01:46:06,360 HYPERTENSION RESEARCH IS THAT 2963 01:46:06,360 --> 01:46:07,720 LTB4 CAUSES ENDOTHELIAL 2964 01:46:07,720 --> 01:46:08,720 APOPTOSIS AND TRANSFORMATION. 2965 01:46:08,720 --> 01:46:13,240 WE GOT PAIRED UP WITH STAN 2966 01:46:13,240 --> 01:46:14,960 ROCKSON RIGHT AROUND 2010, 2011, 2967 01:46:14,960 --> 01:46:16,600 TO TRY AND EXPLORE THESE 2968 01:46:16,600 --> 01:46:18,240 PATHWAYS EVEN AS THE KETOPROFEN 2969 01:46:18,240 --> 01:46:21,600 TRIAL WAS BEGINNING TO OCCUR. 2970 01:46:21,600 --> 01:46:23,480 AND TO STUDY LYMPHEDEMA, LET ME 2971 01:46:23,480 --> 01:46:25,440 JUST BRIEFLY REVIEW THE TAIL 2972 01:46:25,440 --> 01:46:27,320 MODEL, WHERE WE CAN EITHER DO A 2973 01:46:27,320 --> 01:46:29,920 SHAM SURGERY WITH A SURFACE NICK 2974 01:46:29,920 --> 01:46:34,880 OF THE TAIL, OR WE CAN CUT THE 2975 01:46:34,880 --> 01:46:36,200 LYMPHATIC TRUNKS ON BOTH SIDES, 2976 01:46:36,200 --> 01:46:40,080 AND THIS LEADS TO A STEREO TYPIC 2977 01:46:40,080 --> 01:46:41,080 INCREASE IN THE GIRTH OF THE 2978 01:46:41,080 --> 01:46:43,120 TAIL THAT MIMICS LYMPHEDEMA MUCH 2979 01:46:43,120 --> 01:46:45,200 IN THE WAY THAT DR. ROCKSON 2980 01:46:45,200 --> 01:46:46,080 DESCRIBED. 2981 01:46:46,080 --> 01:46:48,160 NOW IT'S AN INTERESTING MODEL 2982 01:46:48,160 --> 01:46:52,320 BECAUSE YOU DO GET THIS RISE IN 2983 01:46:52,320 --> 01:46:54,240 TAIL VOLUME WHICH OCCURS, THEN 2984 01:46:54,240 --> 01:46:55,800 YOU GET A SLIGHT TAPERING THAT 2985 01:46:55,800 --> 01:46:57,000 OCCURS OVER TIME, BUT THE 2986 01:46:57,000 --> 01:46:58,280 ANIMALS DON'T GENERALLY 2987 01:46:58,280 --> 01:46:58,720 COMPLETELY RESOLVE. 2988 01:46:58,720 --> 01:47:01,880 SO IT'S A GOOD MODEL TO STUDY 2989 01:47:01,880 --> 01:47:03,640 LYMPHEDEMA THAT MIGHT BE 2990 01:47:03,640 --> 01:47:04,640 RELEVANT TO THE CLINICAL 2991 01:47:04,640 --> 01:47:07,200 CONDITION. 2992 01:47:07,200 --> 01:47:09,360 SO WE INTERROGATED THIS MODEL 2993 01:47:09,360 --> 01:47:12,000 USING A VARIETY OF APPROACHES. 2994 01:47:12,000 --> 01:47:16,120 IF WE USE IBUPROFEN WHICH JUST 2995 01:47:16,120 --> 01:47:20,040 TARGETS COX1, COX2, WE SAW NO 2996 01:47:20,040 --> 01:47:21,440 BENEFIT TO THE TREATMENT. 2997 01:47:21,440 --> 01:47:24,600 BUT IF WE USED KETOPROFEN JUST 2998 01:47:24,600 --> 01:47:27,560 LIKE THE HUMAN CONDITION WHICH 2999 01:47:27,560 --> 01:47:30,840 BLOCKS BOTH COX-1 AND COX-2 AS A 3000 01:47:30,840 --> 01:47:32,480 DUAL INHIBITOR, IT WAS 3001 01:47:32,480 --> 01:47:37,200 EFFECTIVE. 3002 01:47:37,200 --> 01:47:42,880 AS WAS SIE. ILEUTON BUT WHEN YOU 3003 01:47:42,880 --> 01:47:50,360 BLOCK THE CYSLTs, IT WAS NOT 3004 01:47:50,360 --> 01:47:50,960 EFFECTIVE. 3005 01:47:50,960 --> 01:47:54,880 IF WE USED -- WHICH BLOCK THE 3006 01:47:54,880 --> 01:47:55,960 LTB4, WE SAW EFFECTIVE TREAT M 3007 01:47:55,960 --> 01:47:56,520 OF THE DISEASE. 3008 01:47:56,520 --> 01:47:58,160 SO WHAT DOES THIS LOOK LIKE? 3009 01:47:58,160 --> 01:47:59,160 IN OUR LYMPHEDEMA TAIL MODEL, 3010 01:47:59,160 --> 01:48:03,680 WHAT YOU CAN SEE IS THIS 3011 01:48:03,680 --> 01:48:05,320 INCREASED INTERSTITIAL FLUID, 3012 01:48:05,320 --> 01:48:10,760 DERMAL THICKENING, AND IF YOU 3013 01:48:10,760 --> 01:48:14,280 TREAT WITH AN LTB4 ANTAGONIST, 3014 01:48:14,280 --> 01:48:15,400 YOU SEE YOU CAN HELP PREVENT 3015 01:48:15,400 --> 01:48:19,160 THIS, AND IT LOOKS CLOSE TO THE 3016 01:48:19,160 --> 01:48:19,720 SHAM. 3017 01:48:19,720 --> 01:48:24,440 NOW, WE CAN INJECT EVANS BLUE TO 3018 01:48:24,440 --> 01:48:26,520 GAUGE HOW WELL IT'S TAKEN UP AND 3019 01:48:26,520 --> 01:48:28,600 SHOW IN A SALINE-TREATED 3020 01:48:28,600 --> 01:48:30,120 LYMPHATIC SURGERY MODEL, YOU 3021 01:48:30,120 --> 01:48:31,200 DON'T GET GOOD RESORPTION DISTAL 3022 01:48:31,200 --> 01:48:33,400 TO WHERE THE LYMPHATIC TRUNKS 3023 01:48:33,400 --> 01:48:34,920 HAVE BEEN CUT. 3024 01:48:34,920 --> 01:48:37,320 BUT IN AN ANIMAL WHERE YOU'VE 3025 01:48:37,320 --> 01:48:44,080 TREATED WITH LEUKOTRIENE B4, YOU 3026 01:48:44,080 --> 01:48:45,800 SEE THIS SUGGESTING IT MIGHT BE 3027 01:48:45,800 --> 01:48:46,680 AN IMPACTFUL TREATMENT. 3028 01:48:46,680 --> 01:48:48,560 SO I'M GOING TO DO A SLIGHT 3029 01:48:48,560 --> 01:48:50,160 DETOUR HERE JUST TO TALK ABOUT 3030 01:48:50,160 --> 01:48:52,040 WHY WE DO SCIENCE AND WE'RE NOT 3031 01:48:52,040 --> 01:48:55,280 ALWAYS RIGHT WITH OUR 3032 01:48:55,280 --> 01:48:57,000 HYPOTHESES, BUT IT CAN LEAD TO 3033 01:48:57,000 --> 01:48:59,760 INTERESTING DISCOVERIES. 3034 01:48:59,760 --> 01:49:05,240 SO WE FOUND -- YOU MIGHT EX-MECT 3035 01:49:05,240 --> 01:49:06,920 GIVEN OUR DISCOVERIES THAT IF 3036 01:49:06,920 --> 01:49:13,120 YOU USE A 5-LO OR LTB KNOCKOUT 3037 01:49:13,120 --> 01:49:14,240 PLOWS THEY WOULD BE PROTECTED 3038 01:49:14,240 --> 01:49:15,400 FROM LYMPHEDEMA, YOU'RE 3039 01:49:15,400 --> 01:49:17,680 ESSENTIALLY BLOCKING LTB4 AT A 3040 01:49:17,680 --> 01:49:18,960 MORE ABSOLUTE LEVEL. 3041 01:49:18,960 --> 01:49:21,280 INSTEAD, WE FOUND IN A COMPLETE 3042 01:49:21,280 --> 01:49:23,320 ABSENCE OF NORMAL LTB4 SIGNALING 3043 01:49:23,320 --> 01:49:25,800 THE TAILS BECAME EDEMATOUS AND 3044 01:49:25,800 --> 01:49:26,320 NECROTIC. 3045 01:49:26,320 --> 01:49:29,200 SOME OF THEM EVEN FELL OFF. 3046 01:49:29,200 --> 01:49:32,040 WHICH SUGGESTED TO US THAT 3047 01:49:32,040 --> 01:49:34,320 SOMEHOW INHIBITING LTB4 A FEW 3048 01:49:34,320 --> 01:49:38,520 DAYS AFTER SURGERY WAS DIFFERENT 3049 01:49:38,520 --> 01:49:40,560 IN THE COMPLETE ABSENCE OF LTB4. 3050 01:49:40,560 --> 01:49:45,240 AND SO WHAT WE FOUND IN VITRO 3051 01:49:45,240 --> 01:49:46,880 WAS THAT AT PHYSIOLOGIC 3052 01:49:46,880 --> 01:49:49,480 CONCENTRATIONS OF 5 TO 10 3053 01:49:49,480 --> 01:49:55,080 NANOMOLAR, LTB4 IS ACTUALLY PRO 3054 01:49:55,080 --> 01:49:55,720 LYMPHANGIOGENIC, WHEREAS WHEN 3055 01:49:55,720 --> 01:49:57,040 YOU GET INTO THE TOXIC REGIONS 3056 01:49:57,040 --> 01:50:01,120 THAT BUILD UP OVER TIME, LTB4 IS 3057 01:50:01,120 --> 01:50:06,320 HARMFUL, AND BLOCKS NORMAL 3058 01:50:06,320 --> 01:50:07,280 LYMPHATIC ENDOTHELIAL CELL 3059 01:50:07,280 --> 01:50:10,120 FUNCTION AND CAN CAUSE 3060 01:50:10,120 --> 01:50:10,880 ENDOTHELIAL CELL DEATH, MUCH 3061 01:50:10,880 --> 01:50:14,120 LIKE WE SEE IN PULMONARY 3062 01:50:14,120 --> 01:50:14,560 ENDOTHELIAL CELLS. 3063 01:50:14,560 --> 01:50:20,920 SO ALL OF THIS WORK LED TO TWO 3064 01:50:20,920 --> 01:50:22,760 CLINICAL TRIALS, ONE WHICH IS 3065 01:50:22,760 --> 01:50:24,080 ALREADY BEING PERFORMED. 3066 01:50:24,080 --> 01:50:26,280 THE ONE STAN DESCRIBED WAS 3067 01:50:26,280 --> 01:50:27,800 UNDERPOWERED, BUT WE HAD SOME 3068 01:50:27,800 --> 01:50:29,000 ANECDOTAL COMPELLING RESPONSES 3069 01:50:29,000 --> 01:50:31,040 WHICH PROMPTED A NEW TRIAL THAT 3070 01:50:31,040 --> 01:50:33,800 WAS MORE LIMITED BUT A LARGER 3071 01:50:33,800 --> 01:50:38,160 GROUP OF PATIENTS AND MORE 3072 01:50:38,160 --> 01:50:39,360 FOCUSED AND CONDUCTED AT 3073 01:50:39,360 --> 01:50:40,560 STANFORD, WHICH STAN IS LEADING. 3074 01:50:40,560 --> 01:50:42,960 SO EVEN AS WE'RE EVALUATING 3075 01:50:42,960 --> 01:50:44,080 THESE INFLAMMATORY PATHWAYS, OUR 3076 01:50:44,080 --> 01:50:45,520 GROUP IS ALSO INTERESTED IN 3077 01:50:45,520 --> 01:50:46,800 HYPOXIC SIGNALING, AND WE KNOW 3078 01:50:46,800 --> 01:50:53,040 THAT IT'S IMPORTANT IN DRIVING 3079 01:50:53,040 --> 01:50:54,120 ANGIOGENESIS VIA TRANSCRIPTION 3080 01:50:54,120 --> 01:50:56,440 FACTORS KNOWN AS THE HYPOXIA 3081 01:50:56,440 --> 01:50:59,040 INDUCIBLE FACTORS, OR HIFs. 3082 01:50:59,040 --> 01:51:00,520 WE WONDERED WHETHER OR NOT THE 3083 01:51:00,520 --> 01:51:01,760 HIFs ARE IMPORTANT IN 3084 01:51:01,760 --> 01:51:04,760 LYMPHATIC REPAIR. 3085 01:51:04,760 --> 01:51:10,760 SO AGAIN, XINGUA JIANG IN OUR 3086 01:51:10,760 --> 01:51:13,840 LAB CONDUCTED THESE STUDIES AND 3087 01:51:13,840 --> 01:51:16,960 SURPRISINGLY WE SAW IN HUMAN 3088 01:51:16,960 --> 01:51:18,200 LYMPHEDEMA SKIN WE SEE A 3089 01:51:18,200 --> 01:51:21,600 RELATIVELY INCREASED AMOUNT 3090 01:51:21,600 --> 01:51:23,360 LINING ENDOTHELIAL CELLS BUT A 3091 01:51:23,360 --> 01:51:25,760 DECREASED AMOUNT OF HIF2 ALPHA. 3092 01:51:25,760 --> 01:51:28,400 WE KNEW THAT HIF2 ALPHA WAS ALSO 3093 01:51:28,400 --> 01:51:31,360 AN IMPORTANT SURVIVAL FACTOR IN 3094 01:51:31,360 --> 01:51:32,680 PULMONARY ENDOTHELIAL CELLS. 3095 01:51:32,680 --> 01:51:36,440 SO WE QUESTIONED WHETHER OR NOT 3096 01:51:36,440 --> 01:51:38,640 THIS COULD HAVE A ROLE IN WHY 3097 01:51:38,640 --> 01:51:40,080 PATIENTS DEVELOPED AND 3098 01:51:40,080 --> 01:51:44,520 PROPAGATED THEIR LYMPHEDEMA. 3099 01:51:44,520 --> 01:51:46,320 NOW IF WE USE THE MOUSE TAIL 3100 01:51:46,320 --> 01:51:47,440 MODEL WHICH I'VE ALREADY 3101 01:51:47,440 --> 01:51:48,640 DESCRIBED TO YOU WHERE YOU GET 3102 01:51:48,640 --> 01:51:49,880 THIS INCREASE AT ABOUT TWO WEEKS 3103 01:51:49,880 --> 01:51:51,680 AND GRA ACTUAL RESOLUTION, IF WE 3104 01:51:51,680 --> 01:51:54,200 USE THAT MODEL, WE INDEED FIND 3105 01:51:54,200 --> 01:52:00,840 THAT YOU GET INCREASED AMOUNTS 3106 01:52:00,840 --> 01:52:05,560 RELATIVELY OF HIV-1 ALPHA IN THE 3107 01:52:05,560 --> 01:52:12,720 LYMPHATICS BUT YOU SEE -- IN THE 3108 01:52:12,720 --> 01:52:13,320 ADVANCED LYMPHEDEMA TAIL. 3109 01:52:13,320 --> 01:52:15,600 THE TAIL MODEL AGAIN SEEMS TO 3110 01:52:15,600 --> 01:52:18,440 REPLICATE THE HUMAN CONDITION. 3111 01:52:18,440 --> 01:52:20,400 SO THE NEXT THING WE DID WAS TO 3112 01:52:20,400 --> 01:52:25,960 DEVELOP A GENETIC KNOCKOUT OF 3113 01:52:25,960 --> 01:52:29,360 LYMPHATIC ENDOTHELIAL CELL 3114 01:52:29,360 --> 01:52:30,440 HIF2 ALPHA, AND WE ALSO 3115 01:52:30,440 --> 01:52:32,600 DEVELOPED THESE WITH HIF1 ALPHA. 3116 01:52:32,600 --> 01:52:35,760 WE ALSO DEVELOPED OVEREXPRESSING 3117 01:52:35,760 --> 01:52:38,160 HIF1 AND HIF2 ALPHA BUT I WON'T 3118 01:52:38,160 --> 01:52:39,480 BE PRESENTING THAT DATA TODAY. 3119 01:52:39,480 --> 01:52:45,800 AND WE DEVELOPED THESE BY 3120 01:52:45,800 --> 01:52:55,440 CROSSING PROX1-CRE ER T2 WITH 3121 01:52:55,440 --> 01:53:01,000 HIF 1 AND HIF 2 TRANS GENE. 3122 01:53:01,000 --> 01:53:02,440 AT A DAY WHEN WE NORMALLY WOULD 3123 01:53:02,440 --> 01:53:04,200 EXPECT A GROWTH OF THE 3124 01:53:04,200 --> 01:53:05,440 LYMPHATICS TOWARD EACH OTHER AT 3125 01:53:05,440 --> 01:53:11,880 THE DORSAL MIDLINE. 3126 01:53:11,880 --> 01:53:14,600 WHAT WE SEE IS THESE EMBRYOS AT 3127 01:53:14,600 --> 01:53:17,120 DAY E16.5 HAVE DORSAL EDEMA, 3128 01:53:17,120 --> 01:53:20,120 WHICH CAN BE INDICATIVE OF -- OR 3129 01:53:20,120 --> 01:53:22,320 IS A REPLICATE FOR LYMPHEDEMA, 3130 01:53:22,320 --> 01:53:28,160 AND A FAILURE TO CLOSE THIS 3131 01:53:28,160 --> 01:53:31,960 MIDLINE LYMPHATIC VESSEL FUSION, 3132 01:53:31,960 --> 01:53:34,640 SUGGESTING THAT LYMPHATIC 3133 01:53:34,640 --> 01:53:36,320 ENDOTHELIAL HIF 2 ALPHA IS 3134 01:53:36,320 --> 01:53:37,720 IMPORTANT FOR DERMAL LYMPHATIC 3135 01:53:37,720 --> 01:53:43,640 DEVELOPMENT. 3136 01:53:43,640 --> 01:53:47,160 IF YOU EVALUATE THESE ANIMALS 2N 3137 01:53:47,160 --> 01:53:49,280 INJECTION, WHAT YOU FIND IS THE 3138 01:53:49,280 --> 01:53:51,200 EVANS BLUE DYE IS TAKEN UP 3139 01:53:51,200 --> 01:53:53,400 NORMALLY AND RESORBED IN THE 3140 01:53:53,400 --> 01:53:57,560 WILD TYPE ANIMAL COMPARED TO THE 3141 01:53:57,560 --> 01:54:00,360 ENDOTHELIAL KNOCKOUT, LYMPHATIC 3142 01:54:00,360 --> 01:54:01,920 ENDOTHELIAL KNOCKOUT HIF 3143 01:54:01,920 --> 01:54:04,400 2 ANIMAL, AGAIN SUGGESTING THAT 3144 01:54:04,400 --> 01:54:08,000 THESE DEFICIENCIES CARRY ON INTO 3145 01:54:08,000 --> 01:54:09,800 LIFE, POSTNATAL LIFE. 3146 01:54:09,800 --> 01:54:13,200 OKAY. 3147 01:54:13,200 --> 01:54:17,800 SO BAYICALLY WHAT WE BE 3148 01:54:17,800 --> 01:54:21,200 IS HIF 2 DEFICIENCY CAUSES 3149 01:54:21,200 --> 01:54:22,520 LYMPHATIC DYSFUNCTION IN THESE 3150 01:54:22,520 --> 01:54:26,000 ANIMALS, AND THEY DEVELOP 3151 01:54:26,000 --> 01:54:27,320 INCREASED TAIL LYMPHEDEMA, AND 3152 01:54:27,320 --> 01:54:31,800 THIS BRIEFLY SUMMARIZES OUR 3153 01:54:31,800 --> 01:54:32,480 EXPERIENCE. 3154 01:54:32,480 --> 01:54:35,840 INTERESTINGLY, WE CAN REPLICATE 3155 01:54:35,840 --> 01:54:40,240 AND RESCUE THESE ANIMALS FROM 3156 01:54:40,240 --> 01:54:42,600 DEVELOPING LYMPHEDEMA BY GIVING 3157 01:54:42,600 --> 01:54:51,680 ADENOTHERAPY, WHICH INCREASES 3158 01:54:51,680 --> 01:54:53,560 ANGIOPOIETIN EXPRESSION. 3159 01:54:53,560 --> 01:54:56,920 I'LL BRIEFLY MENTION WE'RE NOW 3160 01:54:56,920 --> 01:55:05,760 STUDYING SPHINGOCINE SIGNALING, 3161 01:55:05,760 --> 01:55:09,760 SHOWING THAT S1P AND S1P 3162 01:55:09,760 --> 01:55:11,880 METABOLITES ARE DECREASED IN 3163 01:55:11,880 --> 01:55:12,520 LYMPHATIC ENDOTHELIAL CELLS. 3164 01:55:12,520 --> 01:55:17,560 AND THIS IS THE WORK OF OUR 3165 01:55:17,560 --> 01:55:18,000 LABORATORY. 3166 01:55:18,000 --> 01:55:19,640 WE'VE ALSO GENERATED THESE MICE 3167 01:55:19,640 --> 01:55:22,680 THAT ARE DEFICIENT IN 3168 01:55:22,680 --> 01:55:24,280 S1PR1 SIGNALING AND SHOW THAT IN 3169 01:55:24,280 --> 01:55:27,280 THE ABSENCE OF NORMAL S1P 3170 01:55:27,280 --> 01:55:28,640 SIGNALING, WE GET AN 3171 01:55:28,640 --> 01:55:34,960 EXACERBATION OF LYMPHEDEMA. 3172 01:55:34,960 --> 01:55:37,520 WE FINALLY ATTRIBUTE THIS TO A 3173 01:55:37,520 --> 01:55:42,160 DEFECT IN THE NORMAL -- BRINGING 3174 01:55:42,160 --> 01:55:43,600 IN OF T-CELLS INTO THE 3175 01:55:43,600 --> 01:55:45,680 LYMPHATICS WITH ACTIVATION OF 3176 01:55:45,680 --> 01:55:47,000 T-CELLS, AND I DON'T REALLY HAVE 3177 01:55:47,000 --> 01:55:48,400 TIME TO SHOW THIS TO YOU TODAY. 3178 01:55:48,400 --> 01:55:51,360 SO IN CONCLUSION, THE LYMPHATIC 3179 01:55:51,360 --> 01:55:53,520 CIRCULATION HAS A VARIETY OF 3180 01:55:53,520 --> 01:55:55,160 UNIQUE FUNCTIONS THAT ARE 3181 01:55:55,160 --> 01:55:57,800 RELATIVELY UNDERSTUDIED, AND WE 3182 01:55:57,800 --> 01:56:02,160 NEED OBVIOUSLY DRUG TARGETS. 3183 01:56:02,160 --> 01:56:03,840 THERE ARE KEY SIGNALING PATHWAYS 3184 01:56:03,840 --> 01:56:05,800 THAT ARE EMERGING WHICH INCLUDE 3185 01:56:05,800 --> 01:56:08,840 HIF 2 ALPHA AND S1P. 3186 01:56:08,840 --> 01:56:11,160 IT'S EVIDENT THAT LYMPHATIC 3187 01:56:11,160 --> 01:56:14,160 VASCULATURE REGULATES T-CELL 3188 01:56:14,160 --> 01:56:14,600 ACTIVATION. 3189 01:56:14,600 --> 01:56:18,920 SO IT'S NOT JUST -- THE 3190 01:56:18,920 --> 01:56:20,040 LYMPHATICS ARE IMPORTANT IN THE 3191 01:56:20,040 --> 01:56:25,600 VESSEL FORCE FOR ACTIVATING N 3192 01:56:25,600 --> 01:56:26,040 T-CELLS. 3193 01:56:26,040 --> 01:56:31,840 WE NEED TO THINK WE NEED TOT 3194 01:56:31,840 --> 01:56:32,880 EVALUATING THESE PATHWAYS OF 3195 01:56:32,880 --> 01:56:36,480 INJURY AND REPAIR SO WE CAN MORE 3196 01:56:36,480 --> 01:56:37,280 COMPLETELY UNDERSTAND THIS SO WE 3197 01:56:37,280 --> 01:56:38,560 CAN DEVELOP ORAL DRUGS. 3198 01:56:38,560 --> 01:56:40,000 SO WE NEED TO INTEGRATE THESE 3199 01:56:40,000 --> 01:56:40,560 PATHWAYS. 3200 01:56:40,560 --> 01:56:43,120 WE NEED TO BETTER UNDERSTAND THE 3201 01:56:43,120 --> 01:56:45,880 TRANSCRIPTIONAL MACHINERY OF 3202 01:56:45,880 --> 01:56:47,200 LYMPHANGIOGENIC PATHWAYS AND 3203 01:56:47,200 --> 01:56:49,440 CHARACTERIZE THE ROLE OF 3204 01:56:49,440 --> 01:56:50,720 LYMPHATIC VASCULATURE IN IMMUNE 3205 01:56:50,720 --> 01:56:51,480 ACTIVATION. 3206 01:56:51,480 --> 01:56:55,760 AND FINALLY, WE NEED TO DEVELOP 3207 01:56:55,760 --> 01:56:58,360 THERAPEUTIC LYMPHANGIOGENESIS 3208 01:56:58,360 --> 01:57:00,440 CONCEPTS, IN SOLID ORGAN 3209 01:57:00,440 --> 01:57:01,840 TRANSPLANTS, WHICH WE'RE 3210 01:57:01,840 --> 01:57:03,840 INVESTIGATING, AND IN BREAST 3211 01:57:03,840 --> 01:57:05,280 CANCER PATIENTS, WE'VE HEARD 3212 01:57:05,280 --> 01:57:06,880 ABOUT ELEGANT LYMPH NODE 3213 01:57:06,880 --> 01:57:08,960 TRANSPLANT THERAPIES TODAY. 3214 01:57:08,960 --> 01:57:14,000 CAN WE PREEMPTIVELY TARGET THESE 3215 01:57:14,000 --> 01:57:15,520 PATIENTS SO THEY DON'T DEVELOP 3216 01:57:15,520 --> 01:57:15,840 LYMPHEDEMA? 3217 01:57:15,840 --> 01:57:20,040 I REALLY WANT TO HIGHLIGHT AMY, 3218 01:57:20,040 --> 01:57:24,400 XINGUA, DONGEON, RHINE AND LAN 3219 01:57:24,400 --> 01:57:26,200 AND OUR COLLABORATIONS WITH 3220 01:57:26,200 --> 01:57:26,480 DR. ROCKSON. 3221 01:57:26,480 --> 01:57:30,320 >> THANK YOU FOR YOUR BEAUTIFUL 3222 01:57:30,320 --> 01:57:34,040 TALK, NICE SECTION ON EACH OF 3223 01:57:34,040 --> 01:57:35,360 THESE MECHANISMS. 3224 01:57:35,360 --> 01:57:40,880 OUR NEXT SPEAKER IS RAGHU 3225 01:57:40,880 --> 01:57:41,880 KATARU, SPEAKING ABOUT 3226 01:57:41,880 --> 01:57:43,520 MECHANISMS OF FIBROSIS AND 3227 01:57:43,520 --> 01:57:44,640 LYMPHATIC DYSFUNCTION IN 3228 01:57:44,640 --> 01:57:45,880 SECONDARY LYMPHEDEMA. 3229 01:57:45,880 --> 01:57:46,920 RAGHU, THE FLOOR IS YOURS. 3230 01:57:46,920 --> 01:57:49,120 >> I HOPE YOU GUYS CAN HEAR ME 3231 01:57:49,120 --> 01:57:49,680 PROPERLY, RIGHT? 3232 01:57:49,680 --> 01:57:50,600 >> YES, WE CAN. 3233 01:57:50,600 --> 01:57:51,960 >> AND THE SLIDES ARE GOOD. 3234 01:57:51,960 --> 01:57:52,160 OKAY. 3235 01:57:52,160 --> 01:57:52,800 >> YEP. 3236 01:57:52,800 --> 01:57:53,560 >> THANK YOU, TIM. 3237 01:57:53,560 --> 01:57:55,760 THANK YOU FOR THE INTRODUCTION. 3238 01:57:55,760 --> 01:58:02,640 IT'S REALLY AN HONOR TO BE HERE 3239 01:58:02,640 --> 01:58:04,280 TO SHOW AND SHARE SOME OF OUR 3240 01:58:04,280 --> 01:58:05,760 LATEST DATA RELATED TO SECONDARY 3241 01:58:05,760 --> 01:58:07,520 LYMPHEDEMA. 3242 01:58:07,520 --> 01:58:14,720 THIS TALK IS MORE ABOUT A COUPLE 3243 01:58:14,720 --> 01:58:18,760 OF FIBROSIS, A BIT LESS 3244 01:58:18,760 --> 01:58:19,200 ABOUT --, PER SE. 3245 01:58:19,200 --> 01:58:20,440 I WANT TO SAY ALL THE DATA 3246 01:58:20,440 --> 01:58:21,720 THAT'S GOING TO BE SHOWN IN THIS 3247 01:58:21,720 --> 01:58:24,760 TALK IS ACTUALLY UNPUBLISHED, 3248 01:58:24,760 --> 01:58:25,760 UNSUBMITTED OR READY TO BE 3249 01:58:25,760 --> 01:58:26,160 SUBMITTED. 3250 01:58:26,160 --> 01:58:27,640 SO I'M HAPPY TO SHARE AND GET 3251 01:58:27,640 --> 01:58:34,040 SOME FEEDBACK FROM YOU GUYS. 3252 01:58:34,040 --> 01:58:35,560 SO LYMPHEDEMA DOESN'T REQUIRE AN 3253 01:58:35,560 --> 01:58:36,120 INTRODUCTION HERE ANYMORE, 3254 01:58:36,120 --> 01:58:40,240 THANKS TO ALL THE SPEAKERS 3255 01:58:40,240 --> 01:58:40,880 EARLIER. 3256 01:58:40,880 --> 01:58:43,880 BUT ANYHOW, I WOULD LIKE TO GIVE 3257 01:58:43,880 --> 01:58:46,360 A COUPLE -- THE PATHOPHYSIOLOGY 3258 01:58:46,360 --> 01:58:47,640 OF LYMPHEDEMA IS VERY COMPLEX, 3259 01:58:47,640 --> 01:58:50,440 WHERE THE PATHOPHYSIOLOGY 3260 01:58:50,440 --> 01:58:51,720 DISEASE IS CHARACTERIZED BY 3261 01:58:51,720 --> 01:58:53,320 CHRONIC INFLAMMATION AND 3262 01:58:53,320 --> 01:58:55,400 FIBROSIS THAT ACTUALLY AFFECTS 3263 01:58:55,400 --> 01:59:03,280 LYMPH STRUCTURE AND FUNCTION, 3264 01:59:03,280 --> 01:59:09,200 THE LYMPHATICS -- CAN AFFECT 3265 01:59:09,200 --> 01:59:11,160 INFLAMMATION AND FIBROSIS. 3266 01:59:11,160 --> 01:59:12,440 SO THESE TWO COMPONENTS GO HAND 3267 01:59:12,440 --> 01:59:15,040 IN HAND. 3268 01:59:15,040 --> 01:59:17,680 IN TERMS OF OVER THE PAST 10 3269 01:59:17,680 --> 01:59:20,280 YEARS OR SO, OUR LAB HAS BEEN 3270 01:59:20,280 --> 01:59:22,160 FOCUSING ON THE UNDERSTANDING OF 3271 01:59:22,160 --> 01:59:23,240 INFLAMMATORY REACTIONS THAT 3272 01:59:23,240 --> 01:59:24,880 OCCUR IN LYMPHEDEMA, AND WE 3273 01:59:24,880 --> 01:59:27,400 FOUND THAT CD4 POSITIVE CELLS 3274 01:59:27,400 --> 01:59:30,320 THAT ARE ACTUALLY TH2 TYPE 3275 01:59:30,320 --> 01:59:31,640 DIFFERENTIATED PLAY A CRITICAL 3276 01:59:31,640 --> 01:59:32,600 ROLE IN THE PATHOLOGY OF THE 3277 01:59:32,600 --> 01:59:33,720 DISEASE. 3278 01:59:33,720 --> 01:59:39,080 SO OUR RESEARCH -- A QUICK RECAP 3279 01:59:39,080 --> 01:59:41,280 OF WHAT WE HAVE DONE FOR THE 3280 01:59:41,280 --> 01:59:47,720 LAST YEARS IS T-CELL 3281 01:59:47,720 --> 01:59:50,680 PROLIFERATION BY TACROLIM UCHT S 3282 01:59:50,680 --> 01:59:54,880 ARE MAYBE BLOCKING BY IL4 AND 3283 01:59:54,880 --> 01:59:57,600 IL13 MONOCLONAL ANTIBODY 3284 01:59:57,600 --> 02:00:02,400 TREATMENT, BLOCKING -- TO 3285 02:00:02,400 --> 02:00:07,120 INHIBIT FIBROSIS, ROANTLY WE REE 3286 02:00:07,120 --> 02:00:08,080 PUBLISHED THIS PAPER. 3287 02:00:08,080 --> 02:00:08,880 THESE ARE SOME OF THE METHODS 3288 02:00:08,880 --> 02:00:13,040 WHERE WE SHOWED THERE WAS A 3289 02:00:13,040 --> 02:00:14,360 POSITIVE WAY YOU CAN ACTUALLY 3290 02:00:14,360 --> 02:00:15,560 PREVENT LYMPHEDEMA BY THESE 3291 02:00:15,560 --> 02:00:15,960 METHODS. 3292 02:00:15,960 --> 02:00:19,240 SO IN THIS PROCESS, WHAT WE CAME 3293 02:00:19,240 --> 02:00:27,800 ACROSS IN OUR RECENT DATA, THE 3294 02:00:27,800 --> 02:00:30,160 ONE PHENOTYPE WHICH PROMINENTLY 3295 02:00:30,160 --> 02:00:32,600 SHOWED UP IS STRONG UPREGULATION 3296 02:00:32,600 --> 02:00:38,160 OF KERATINS FROM HUMAN SAMPLES 3297 02:00:38,160 --> 02:00:39,760 WHICH WE HAVE PERFORMED RNA SEQ 3298 02:00:39,760 --> 02:00:40,200 ON. 3299 02:00:40,200 --> 02:00:44,360 SO AS YOU CAN SEE THE NUMBER 3300 02:00:44,360 --> 02:00:45,960 HIGHLY UPREGULATED. 3301 02:00:45,960 --> 02:00:48,000 THIS LED US TO THINK THAT MAYBE 3302 02:00:48,000 --> 02:00:51,960 THE KERATIN SIGNATURE SUGGESTS 3303 02:00:51,960 --> 02:00:53,400 THERE'S A -- IN THE PATHOLOGY. 3304 02:00:53,400 --> 02:00:55,600 SO THIS LED US TO THINK A LITTLE 3305 02:00:55,600 --> 02:00:57,880 DEEPER INTO THIS AND SO THESE 3306 02:00:57,880 --> 02:01:05,320 ARE SOME OF THE HISTOLOGY 3307 02:01:05,320 --> 02:01:06,960 IMAGES, THE NORMAL IS NORMAL 3308 02:01:06,960 --> 02:01:07,720 ARM, LYMPHEDEMA IS THE 3309 02:01:07,720 --> 02:01:08,720 LYMPHEDEMA ARM OF THE SAME 3310 02:01:08,720 --> 02:01:10,120 PATIENT. 3311 02:01:10,120 --> 02:01:14,360 SHOWING THAT YOU CAN CLEARLY SEE 3312 02:01:14,360 --> 02:01:17,280 THAT THERE IS A HYPERKERATOSIS 3313 02:01:17,280 --> 02:01:24,320 AND THICKENED EPIDERMIS IN THE 3314 02:01:24,320 --> 02:01:26,120 LYMPHEDEMA INDICATING THERE IS 3315 02:01:26,120 --> 02:01:27,960 DEFINITELY HYPERKERATOSIS 3316 02:01:27,960 --> 02:01:29,160 HAPPENING, BUT THE QUESTION WE 3317 02:01:29,160 --> 02:01:33,280 HAD WAS HOW IT CONTRIBUTES TO 3318 02:01:33,280 --> 02:01:34,200 LYMPHEDEMA PATHOLOGY. 3319 02:01:34,200 --> 02:01:35,280 TO UNDERSTAND THAT WHEN WE DID 3320 02:01:35,280 --> 02:01:46,360 THE RESEARCH, KERATIN KERATN 3321 02:01:46,360 --> 02:01:47,360 DERMATITIS WHICH IS WELL 3322 02:01:47,360 --> 02:01:50,800 STUDIED, THERE'S A STRONG -- 3323 02:01:50,800 --> 02:01:52,200 PLAY AN IMPORTANT ROLE IN THAT. 3324 02:01:52,200 --> 02:01:54,400 SO CONSIDERING THIS, WE THOUGHT 3325 02:01:54,400 --> 02:01:57,320 LYMPHEDEMA BEING A SKIN DISEASE, 3326 02:01:57,320 --> 02:01:58,760 THAT'S WHAT AT LEAST WE BELIEVE, 3327 02:01:58,760 --> 02:02:00,600 AND THEN WE THOUGHT MAYBE, YOU 3328 02:02:00,600 --> 02:02:03,160 KNOW, THERE IS A POSSIBILITY 3329 02:02:03,160 --> 02:02:06,640 THAT KERATINOCYTES PLAY SOME 3330 02:02:06,640 --> 02:02:07,720 ROLE IN THE LYMPHEDEMA TOO. 3331 02:02:07,720 --> 02:02:09,480 SO TO UNDERSTAND THAT, THIS IS A 3332 02:02:09,480 --> 02:02:11,000 HUMAN DATA WHERE WE GOT SAMPLES 3333 02:02:11,000 --> 02:02:15,560 FROM A HUMAN LYMPHEDEMA 3334 02:02:15,560 --> 02:02:16,280 PATIENTS, BIOPSY SAMPLES WHERE 3335 02:02:16,280 --> 02:02:18,680 WE DID HISTOLOGY AND -- 3336 02:02:18,680 --> 02:02:20,600 INITIALLY TO UNDERSTAND THE 3337 02:02:20,600 --> 02:02:20,960 HYPERKERATOSIS. 3338 02:02:20,960 --> 02:02:23,160 AS YOU CAN SEE, THERE'S A 3339 02:02:23,160 --> 02:02:24,160 SIGNIFICANT HYPERKERATOSIS IN 3340 02:02:24,160 --> 02:02:28,440 THE LYMPHEDEMA PATIENT'S SKIN. 3341 02:02:28,440 --> 02:02:29,680 INTERESTINGLY, THERE IS AN 3342 02:02:29,680 --> 02:02:31,080 UPREGULATED -- THE PROLIFERATION 3343 02:02:31,080 --> 02:02:39,520 OF EPIDERMAL CELLS, 3344 02:02:39,520 --> 02:02:42,360 KERATINOCYTES IS VERY HIGH -- IN 3345 02:02:42,360 --> 02:02:44,240 HEALTHY SKIN IS HIGHLY 3346 02:02:44,240 --> 02:02:45,280 UPREGULATED AND ALSO KERATIN 14 3347 02:02:45,280 --> 02:02:47,960 WHICH IS A MARKER OF VESSEL CELL 3348 02:02:47,960 --> 02:02:49,920 LAYER IS ACTUALLY PRESENTED 3349 02:02:49,920 --> 02:02:51,880 THROUGHOUT THE WHOLE EPIDERMIS, 3350 02:02:51,880 --> 02:02:54,840 INDICATING OR SUPPORTING OUR RNA 3351 02:02:54,840 --> 02:02:57,680 SEQ DATA FOR EXPRESS OF 3352 02:02:57,680 --> 02:02:59,760 KERATINS, AND THESE THINGS ARE 3353 02:02:59,760 --> 02:03:01,320 QUANTIFIED BY WESTERN BLOTTING, 3354 02:03:01,320 --> 02:03:02,200 PCR AND OTHER METHODS. 3355 02:03:02,200 --> 02:03:05,000 SO THE NEXT THING IS, OKAY, WE 3356 02:03:05,000 --> 02:03:15,520 SEE A HYPERPLASTIC EPIDERMIS, SO 3357 02:03:16,240 --> 02:03:18,480 WHAT ARE THEY DOING. 3358 02:03:18,480 --> 02:03:23,160 WE STAINED FOR TH2-INDUCING 3359 02:03:23,160 --> 02:03:33,720 CYTOKINES LIKE KLK5, PAR2, TSLP, 3360 02:03:34,320 --> 02:03:37,640 IL-33, LYMPHEDEMA SEEMS TO BE -- 3361 02:03:37,640 --> 02:03:43,400 IN CASE OF LYMPHEDEMA, THESE THY 3362 02:03:43,400 --> 02:03:43,840 UPREGULATED. 3363 02:03:43,840 --> 02:03:45,800 AGAIN, THIS IS QUANTIFIED BY 3364 02:03:45,800 --> 02:03:46,680 OTHER METHODS LIKE WESTERN 3365 02:03:46,680 --> 02:03:50,920 BLOTTING AND PCR, JUST TO 3366 02:03:50,920 --> 02:03:52,040 COLLABORATE OUR -- OF THE DATA. 3367 02:03:52,040 --> 02:03:53,880 SO CONSIDERING THESE CHANGES IN 3368 02:03:53,880 --> 02:03:56,080 THE HUMAN HYPERKERATOSIS IN THE 3369 02:03:56,080 --> 02:03:58,280 HUMAN LYMPHEDEMA SKIN, WE WANTED 3370 02:03:58,280 --> 02:03:59,920 TO SEE WHETHER MOUSE ACTUALLY 3371 02:03:59,920 --> 02:04:03,520 FOLLOWS THE SAME WAY, SO WE 3372 02:04:03,520 --> 02:04:04,840 USED -- I KNOW MOST YOU HAVE 3373 02:04:04,840 --> 02:04:06,880 KNOW THIS MODEL OF TAIL 3374 02:04:06,880 --> 02:04:08,840 LYMPHEDEMA, BUT JUST FOR SOME 3375 02:04:08,840 --> 02:04:10,200 PEOPLE WHO ARE NOT AWARE OF 3376 02:04:10,200 --> 02:04:13,880 THIS, THE DALE TAIL LYMPHEDEL 3377 02:04:13,880 --> 02:04:17,600 WE'RE SHOWING HERE IS WHERE WE 3378 02:04:17,600 --> 02:04:20,880 SURGICALLY REMOVE -- SUPERVISOR 3379 02:04:20,880 --> 02:04:22,920 PICIAL AND -- LYMPHATICS, AND AT 3380 02:04:22,920 --> 02:04:24,360 FOUR TO SIX WEEKS, YOU CAN SEE 3381 02:04:24,360 --> 02:04:25,040 DEVELOPMENT OF LYMPHEDEMA. 3382 02:04:25,040 --> 02:04:29,160 THIS IS ONE OF THE MOST COMMONLY 3383 02:04:29,160 --> 02:04:31,720 USED METHOD, MODEL FOR -- 3384 02:04:31,720 --> 02:04:32,680 MODELS. 3385 02:04:32,680 --> 02:04:33,760 SO OUR TAIL LYMPHEDEMA MODEL 3386 02:04:33,760 --> 02:04:38,040 ALSO SHOWED INCREASED 3387 02:04:38,040 --> 02:04:39,160 HYPERKERATOSIS, INCREASE IN 3388 02:04:39,160 --> 02:04:40,800 PROLIFERATION OF EPIDERMAL 3389 02:04:40,800 --> 02:04:44,040 CELLS, INCREASE OF KERATIN 6 AND 3390 02:04:44,040 --> 02:04:45,640 KERATIN 14 EXPRESSION AS EARLY 3391 02:04:45,640 --> 02:04:46,600 AS TWO WEEKS. 3392 02:04:46,600 --> 02:04:48,560 THIS DATA IS ACTUALLY SIX WEEKS 3393 02:04:48,560 --> 02:04:49,880 DATA, I'M GOING TO SHOW YOU TWO 3394 02:04:49,880 --> 02:04:52,680 WEEKS DATA LATER ON, AND THE 3395 02:04:52,680 --> 02:04:53,880 QUANTIFICATION FOR THAT. 3396 02:04:53,880 --> 02:04:55,600 AND AGAIN, SIMILAR TO HEUL MAN 3397 02:04:55,600 --> 02:04:58,840 DATA, YOU CAN SEE THE 3398 02:04:58,840 --> 02:05:02,880 HYPERPLASTIC EPIDERMIS IS A 3399 02:05:02,880 --> 02:05:07,680 SOURCE OF TH2-INDUCING 3400 02:05:07,680 --> 02:05:12,280 CYTOKINES, THIS INDUCE FIBROSIS 3401 02:05:12,280 --> 02:05:13,520 LIKE -- AND THE QUANTIFICATION 3402 02:05:13,520 --> 02:05:16,200 IS DONE BASED ON RNA SEQ, PCR 3403 02:05:16,200 --> 02:05:17,880 AND WESTERN BLOTTING FROM THE 3404 02:05:17,880 --> 02:05:18,840 MOUSE TISSUE AS WELL. 3405 02:05:18,840 --> 02:05:21,320 SO THE SUMMARY UNTIL THEN WAS 3406 02:05:21,320 --> 02:05:25,600 THAT BOTH -- WE CAN SEE 3407 02:05:25,600 --> 02:05:27,880 HYPERKERATOSIS BOTH IN HUMAN AND 3408 02:05:27,880 --> 02:05:28,880 MOUSE -- FROM EARLY STAGES. 3409 02:05:28,880 --> 02:05:30,840 AS YOU CAN SEE HERE, WE WANTED 3410 02:05:30,840 --> 02:05:35,120 TO SEE -- SINCE WE SEE A 3411 02:05:35,120 --> 02:05:36,680 TH2 SIGNATURE, I WANTED TO SEE 3412 02:05:36,680 --> 02:05:43,440 WHETHER TH2 SIGNATURE PRECEDES 3413 02:05:43,440 --> 02:05:44,640 OUR -- HYPERKERATOSIS. 3414 02:05:44,640 --> 02:05:46,400 AT TWO WEEKS TIME YOU CAN SEE 3415 02:05:46,400 --> 02:05:47,240 HYPERKERATOSIS IN THE TAIL 3416 02:05:47,240 --> 02:05:47,600 MODEL. 3417 02:05:47,600 --> 02:05:48,920 WE DON'T SEE A LOT OF -- 3418 02:05:48,920 --> 02:05:49,680 INFORMATION YET. 3419 02:05:49,680 --> 02:05:52,240 BUT BY SIX WEEKS, HYPERKERATOSIS 3420 02:05:52,240 --> 02:05:55,480 IS HIGHLY PROMINENT, THE TISSUE 3421 02:05:55,480 --> 02:05:57,120 INFLAMMATION ALSO STARTS TO SHOW 3422 02:05:57,120 --> 02:06:02,440 UP INDICATING THAT ACTUALLY THE 3423 02:06:02,440 --> 02:06:05,240 HYPERKERATOSIS PRECEDES T-CELL 3424 02:06:05,240 --> 02:06:07,720 INVOLVEMENT, T-CELL INFILTRATION 3425 02:06:07,720 --> 02:06:09,400 AND T-CELL INFLAMMATION, SOME OF 3426 02:06:09,400 --> 02:06:10,120 THE QUANTIFICATIONS ARE THE 3427 02:06:10,120 --> 02:06:10,680 SAME. 3428 02:06:10,680 --> 02:06:12,000 SO THE NEXT QUESTION IS WHAT 3429 02:06:12,000 --> 02:06:18,440 ASPECT OF LYMPHATIC INJURY 3430 02:06:18,440 --> 02:06:22,760 ACTIVATES KERATINOCYTES WHEN 3431 02:06:22,760 --> 02:06:23,600 PROLIFERATING THEM. 3432 02:06:23,600 --> 02:06:28,520 SO WE THOUGHT MAYBE THE FLUID 3433 02:06:28,520 --> 02:06:31,040 ACCUMULATING IN THE INTERSTITIAL 3434 02:06:31,040 --> 02:06:33,200 SPACES MIGHT HAVE SOMETHING TO 3435 02:06:33,200 --> 02:06:33,360 DO. 3436 02:06:33,360 --> 02:06:35,200 SO WE HAD OPPORTUNITY TO COLLECT 3437 02:06:35,200 --> 02:06:38,280 LYMPHEDEMA FLUID FROM PATIENTS' 3438 02:06:38,280 --> 02:06:41,120 ARM AND WHEN THIS FLUID CULTURED 3439 02:06:41,120 --> 02:06:46,160 WITH HUMAN KERATIN SITES IN 3440 02:06:46,160 --> 02:06:47,440 VITRO, WHEN COCULTURED WITH 3441 02:06:47,440 --> 02:06:51,400 FLUID, YOU CAN SEE PROLIFERATION 3442 02:06:51,400 --> 02:07:00,120 OF KERATINOCYTES -- JUST LIKE 3443 02:07:00,120 --> 02:07:02,000 THE WAY WE HAVE SEEN IN VIVO, 3444 02:07:02,000 --> 02:07:03,840 AND I'M NOT BRINGING ALL THE 3445 02:07:03,840 --> 02:07:05,840 QUANTIFICATIONS HERE TO MAKE IT 3446 02:07:05,840 --> 02:07:16,120 SHORTEN AND CRISP. 3447 02:07:17,040 --> 02:07:18,200 SO 3448 02:07:18,200 --> 02:07:20,400 WE WANTED TO SEE DOES 3449 02:07:20,400 --> 02:07:23,720 INHIBITING PROLIFERATION OF 3450 02:07:23,720 --> 02:07:30,720 KERATINOCYTES RESCUES LYMPHEDEMA 3451 02:07:30,720 --> 02:07:31,120 PHENOTYPE? 3452 02:07:31,120 --> 02:07:37,800 TEAR FLEUN MIGHT ACTS BY 3453 02:07:37,800 --> 02:07:48,320 FILTRATING -- INHIBITING CELL 3454 02:07:49,160 --> 02:07:50,400 PROLIFERATION. 3455 02:07:50,400 --> 02:07:57,160 IT LOOKS LIKE TERIFLUNOMIDE 3456 02:07:57,160 --> 02:07:58,400 SIGNIFICANTLY REDUCED THE TAIL 3457 02:07:58,400 --> 02:08:00,160 VOLUME AS WE CAN SEE BY THE 3458 02:08:00,160 --> 02:08:01,280 QUANITIFICATIONS, AND THE 3459 02:08:01,280 --> 02:08:07,040 REDUCTION OF HAIRP HYPERKERA, 3460 02:08:07,040 --> 02:08:08,360 SOME EFFECTS ARE QUANTIFIED 3461 02:08:08,360 --> 02:08:09,120 HERE. 3462 02:08:09,120 --> 02:08:13,080 SO WE WENT AHEAD AND CHECKED 3463 02:08:13,080 --> 02:08:15,360 WHETHER IT REDUCES NOT ONLY 3464 02:08:15,360 --> 02:08:16,960 HYPERKERATOSIS BUT ALSO REDUCES 3465 02:08:16,960 --> 02:08:20,360 THE PROLIFERATION OF 3466 02:08:20,360 --> 02:08:21,360 KERATINOCYTES, THEIR EXPRESSION 3467 02:08:21,360 --> 02:08:23,880 OF KERATIN 6 AND OTHER KERATIN 3468 02:08:23,880 --> 02:08:25,760 PROTEINS, AND THEIR EXPRESSION 3469 02:08:25,760 --> 02:08:31,880 OF TSLP, IL-33, OTHER -- 3470 02:08:31,880 --> 02:08:33,000 INDUCING CYTOKINES. 3471 02:08:33,000 --> 02:08:34,800 SO THE TAKE-HOME MESSAGE IS THAT 3472 02:08:34,800 --> 02:08:36,520 IN SUMMARY, IF I WANT TO 3473 02:08:36,520 --> 02:08:38,600 SUMMARIZE THIS PART, THERE IS 3474 02:08:38,600 --> 02:08:41,000 LYMPHATIC INJURY AND THEN 3475 02:08:41,000 --> 02:08:44,480 THERE'S INFLAMMATORY CYTOKINES 3476 02:08:44,480 --> 02:08:50,400 AND PROTEASES AND LYMPHATIC 3477 02:08:50,400 --> 02:08:52,720 FLUID, THEY COME IN TOUCH, THEY 3478 02:08:52,720 --> 02:08:56,520 GET ACTIVATED, THERE IS 3479 02:08:56,520 --> 02:08:58,120 PROLIFERATION OF HYPERKERATOSIS 3480 02:08:58,120 --> 02:09:02,720 AND THERE IS DSLP AND IL-33 AND 3481 02:09:02,720 --> 02:09:04,360 OTHER -- CYTOKINES THAT ACTUALLY 3482 02:09:04,360 --> 02:09:07,320 CAN HELP DIFFERENTIATION OF 3483 02:09:07,320 --> 02:09:10,600 TH2 CELLS AND THEN HELPING 3484 02:09:10,600 --> 02:09:13,840 FIBROSIS AND DAMAGE TO LECs 3485 02:09:13,840 --> 02:09:14,960 WHICH WE HAVE SHOWN BEFORE. 3486 02:09:14,960 --> 02:09:17,480 SO THIS IS ONE MECHANISM WHERE 3487 02:09:17,480 --> 02:09:19,680 POTENTIALLY KERATINOCYTES IN 3488 02:09:19,680 --> 02:09:21,720 LYMPHEDEMA CONTRIBUTE TO THE 3489 02:09:21,720 --> 02:09:23,080 PATHOLOGY OF LYMPHEDEMA FIBROSIS 3490 02:09:23,080 --> 02:09:26,040 AND MAYBE INDIRECTLY -- 3491 02:09:26,040 --> 02:09:27,680 DYSFUNCTION. 3492 02:09:27,680 --> 02:09:29,120 HOW ELSE HYPERKERATOSIS 3493 02:09:29,120 --> 02:09:32,920 CONTRIBUTES TO FIBROSIS IN 3494 02:09:32,920 --> 02:09:33,480 LYMPHEDEMA? 3495 02:09:33,480 --> 02:09:36,080 IN DOING THIS WORK, WE NOTICED 3496 02:09:36,080 --> 02:09:38,200 THE KERATINOCYTES, THIS IS AGAIN 3497 02:09:38,200 --> 02:09:40,520 HUMAN DATA, THE HUMAN LYMPHEDEMA 3498 02:09:40,520 --> 02:09:46,640 SKIN ACTUALLY HAS SIGNIFICANT 3499 02:09:46,640 --> 02:09:48,640 HYPERKERATOSIS AND RETE RIDGE 3500 02:09:48,640 --> 02:09:49,760 FORMATION, THESE PROJECTIONS OF 3501 02:09:49,760 --> 02:09:54,320 THE SKIN, AND THE CELLS IN THE 3502 02:09:54,320 --> 02:09:56,360 BASAL LAYER OF EPIDERMIS SEEMS 3503 02:09:56,360 --> 02:09:58,840 TO BE USING THEIR -- POLARITY AS 3504 02:09:58,840 --> 02:10:02,560 SHOWN IN THESE HIGH 3505 02:10:02,560 --> 02:10:03,120 MAGNIFICATION IMAGES. 3506 02:10:03,120 --> 02:10:05,440 OF COURSE THERE IS A SUBDERMAL 3507 02:10:05,440 --> 02:10:08,520 POSITION, AND MORE IMPORTANTLY, 3508 02:10:08,520 --> 02:10:18,360 WE SEE A LOT OF VIMENTIN 3509 02:10:18,360 --> 02:10:28,880 POSITIVE CELLS, SO THIS LED US 3510 02:10:31,240 --> 02:10:34,760 TO THINK WHETHER IS THERE ANY 3511 02:10:34,760 --> 02:10:36,640 POSSIBILITY OF EMT HAPPENING IN 3512 02:10:36,640 --> 02:10:40,920 LYMPHEDEMA. 3513 02:10:40,920 --> 02:10:43,200 EMT IS A PHYSIOLOGICAL PROCESS 3514 02:10:43,200 --> 02:10:48,120 WHERE THE EPITHELIAL CELLS ARE 3515 02:10:48,120 --> 02:10:50,560 TRANSITIONED INTO MESENCHYMAL 3516 02:10:50,560 --> 02:10:50,960 CELLS. 3517 02:10:50,960 --> 02:10:53,560 BY LOSING -- MARKERS AND 3518 02:10:53,560 --> 02:10:55,240 GAINING -- MARKERS, IT'S SEEN IN 3519 02:10:55,240 --> 02:10:59,880 WOUND HEALING AND CANCER -- WHAT 3520 02:10:59,880 --> 02:11:01,560 WE NOTICE IS A LOT OF THESE IN 3521 02:11:01,560 --> 02:11:04,120 THE BASAL LAYER DON'T EXPRESS 3522 02:11:04,120 --> 02:11:05,760 EPIDERMAL MARKERS OR THEY'RE 3523 02:11:05,760 --> 02:11:07,200 LOSING EPIDERMAL MARKERS IN 3524 02:11:07,200 --> 02:11:08,400 HUMAN PATIENT DATA AS WE CAN SEE 3525 02:11:08,400 --> 02:11:10,160 FROM THESE IMAGES. 3526 02:11:10,160 --> 02:11:12,360 THE OTHER EMT INDICATOR IS GAIN 3527 02:11:12,360 --> 02:11:15,960 OF EMT MARKERS ARE MESENCHYMAL 3528 02:11:15,960 --> 02:11:16,240 MARKERS. 3529 02:11:16,240 --> 02:11:22,200 AGAIN, YOU CAN SEE FSP1, MMP9, 3530 02:11:22,200 --> 02:11:24,920 SLUG, ITGB4 AND OTHER 3531 02:11:24,920 --> 02:11:27,080 MESENCHYMAL MARKERS EXPRESSED BY 3532 02:11:27,080 --> 02:11:28,520 THESE BASAL LAYER CELLS, 3533 02:11:28,520 --> 02:11:29,760 INDICATING THERE IS EMT 3534 02:11:29,760 --> 02:11:30,200 HAPPENING. 3535 02:11:30,200 --> 02:11:31,720 THE THIRD ONE IS INDIVIDUAL AND 3536 02:11:31,720 --> 02:11:32,360 CELL MIGRATION. 3537 02:11:32,360 --> 02:11:39,640 YOU CAN SEE PROJECTIONS AND 3538 02:11:39,640 --> 02:11:43,560 PROTRUSIONS, TRYING TO CROSS THE 3539 02:11:43,560 --> 02:11:44,440 BASAL CELL MEMBRANE. 3540 02:11:44,440 --> 02:11:47,080 SO THESE THREE INDICATIONS ARE 3541 02:11:47,080 --> 02:11:48,960 ALSO INDICATORS OF EMT ALSO 3542 02:11:48,960 --> 02:11:50,240 OBSERVED IN TAIL MODEL OF MOUSE, 3543 02:11:50,240 --> 02:11:52,880 NOT JUST IN HUMANS. 3544 02:11:52,880 --> 02:11:56,600 WHICH WE SHOWED HERE BY -- 3545 02:11:56,600 --> 02:11:57,600 QUANTIFIED BY WESTERN BLOTTING 3546 02:11:57,600 --> 02:12:00,520 AND A COUPLE OF OTHER METHODS. 3547 02:12:00,520 --> 02:12:03,960 SO WE WANTED TO SHOW WHETHER -- 3548 02:12:03,960 --> 02:12:05,280 WITH TRANSFERRED THE 3549 02:12:05,280 --> 02:12:12,480 KERATINOCYTES BY USING MOUSE. 3550 02:12:12,480 --> 02:12:17,400 YOU CAN ACTUALLY SEE -- BY SIX 3551 02:12:17,400 --> 02:12:21,760 WEEKS, THERE IS SO MUCH OF -- IN 3552 02:12:21,760 --> 02:12:23,240 THE EPIDERMAL LAYER 3553 02:12:23,240 --> 02:12:29,840 INDICATING -- AND THEN SOME OF 3554 02:12:29,840 --> 02:12:33,000 THE VIMETIN -- UNDERGOING EMT. 3555 02:12:33,000 --> 02:12:37,440 SOME OF THE CELLS IN THE DERMIS 3556 02:12:37,440 --> 02:12:38,600 HAVE ALREADY MIGRATED. 3557 02:12:38,600 --> 02:12:40,440 SO SOME OF THIS EVIDENCE CLEARLY 3558 02:12:40,440 --> 02:12:43,480 SHOWS THERE IS EMT HAPPENING, 3559 02:12:43,480 --> 02:12:45,760 THEN WE CHARACTERIZE 3560 02:12:45,760 --> 02:12:49,480 KERATINOCYTES IN THE FLUID, THEY 3561 02:12:49,480 --> 02:12:54,280 EXPRESS VIMENTIN AND OTHER 3562 02:12:54,280 --> 02:12:56,240 MARKERS, EMT MARKERS. 3563 02:12:56,240 --> 02:12:58,320 THEN EMT HAS A ROLE -- IS ALSO 3564 02:12:58,320 --> 02:13:07,040 REGULATED BY T-CELL BAY TALL, 3565 02:13:07,040 --> 02:13:08,040 INHIBITS LYMPHEDEMA. 3566 02:13:08,040 --> 02:13:10,920 SO WE CHECKED WHAT'S HAPPENING 3567 02:13:10,920 --> 02:13:11,440 HERE. 3568 02:13:11,440 --> 02:13:14,200 AS YOU CAN SEE, THE TGF BETA IS 3569 02:13:14,200 --> 02:13:16,600 CLEARLY EXPRESSED IN THE 3570 02:13:16,600 --> 02:13:18,040 SUBDERMAL REGIONS WHERE WE 3571 02:13:18,040 --> 02:13:22,760 HAVE -- CELLS AND THE PSMAD3 ARE 3572 02:13:22,760 --> 02:13:27,560 DOWNSTREAM -- THE BLOCKING -- 3573 02:13:27,560 --> 02:13:28,800 KERATIN 14 EXPRESSION THICKENING 3574 02:13:28,800 --> 02:13:31,640 OF EPIDERMIS AND ALSO EXPRESSION 3575 02:13:31,640 --> 02:13:39,760 OF EMT MARKERS BY THESE VIMENTIN 3576 02:13:39,760 --> 02:13:42,680 POSITIVE LAYER. 3577 02:13:42,680 --> 02:13:48,600 SO EPIDERMIS UNDERGO EMT AND 3578 02:13:48,600 --> 02:13:50,440 CONTRIBUTE TO SOME OF THE 3579 02:13:50,440 --> 02:13:53,800 FIBROSIS AS OUR DATA SHOWS. 3580 02:13:53,800 --> 02:13:55,720 THE CONCLUSIONS, HYPERKERATOSIS 3581 02:13:55,720 --> 02:13:59,920 IS A PROMINENT FEATURE CH OF 3582 02:13:59,920 --> 02:14:01,360 LYMPHEDEMA IN BOTH HUMAN AND 3583 02:14:01,360 --> 02:14:02,560 MOUSE, KERATINOCYTES ARE THE 3584 02:14:02,560 --> 02:14:05,920 MAJOR SOURCE OF TH2 INDUCING 3585 02:14:05,920 --> 02:14:09,200 CYTOKINES IN LYMPHEDEMA. 3586 02:14:09,200 --> 02:14:09,720 TERIFLUNOMIDE PREVENTS 3587 02:14:09,720 --> 02:14:12,200 LYMPHEDEMA IN KERATINOCYTE 3588 02:14:12,200 --> 02:14:12,920 DEPENDENT WAY. 3589 02:14:12,920 --> 02:14:14,880 FURTHER QUESTIONS AND 3590 02:14:14,880 --> 02:14:16,640 OPPORTUNITIES, WHAT -- THERE ARE 3591 02:14:16,640 --> 02:14:18,880 SEVERAL BUT ONE IMPORTANT THING 3592 02:14:18,880 --> 02:14:20,920 IS, SEEMS LIKE LYMPHEDEMA FLUID 3593 02:14:20,920 --> 02:14:24,000 IS VERY IMPORTANT HERE. 3594 02:14:24,000 --> 02:14:26,960 THE PROTEOMIC -- WHAT IS 3595 02:14:26,960 --> 02:14:29,240 ACTUALLY MAKING THESE CHANGES IN 3596 02:14:29,240 --> 02:14:33,560 THE LEC FIBROBLASTS ARE THESE 3597 02:14:33,560 --> 02:14:36,920 EPITHELIAL CELLS. I WANT TO 3598 02:14:36,920 --> 02:14:41,080 THANK HYEUNG JU PARK, OUR 3599 02:14:41,080 --> 02:14:42,000 RESEARCH ASSISTANT IN THE LAB 3600 02:14:42,000 --> 02:14:43,720 WHO DID ALL THIS WORK FOR THE 3601 02:14:43,720 --> 02:14:45,360 PAST THREE YEARS, AND OF COURSE 3602 02:14:45,360 --> 02:14:48,640 DR. BABAK MEHRARA FOR ALL HIS 3603 02:14:48,640 --> 02:14:51,680 HELP AND TAKING CARE OF THE LAB, 3604 02:14:51,680 --> 02:14:55,880 AND THEN OUR CLINICAL ATTENDING 3605 02:14:55,880 --> 02:14:57,080 PHYSICIANS AND PREVIOUS LAB 3606 02:14:57,080 --> 02:14:57,840 MEMBERS. 3607 02:14:57,840 --> 02:14:59,120 AND OUR FUNDING SOURCE. 3608 02:14:59,120 --> 02:15:00,120 THANK YOU VERY MUCH. 3609 02:15:00,120 --> 02:15:01,680 I WOULD LIKE TO TAKE SOME 3610 02:15:01,680 --> 02:15:04,520 QUESTIONS LATER. 3611 02:15:04,520 --> 02:15:05,840 >> GREAT, THANK YOU, RAGHU. 3612 02:15:05,840 --> 02:15:07,840 IF YOU CAN STOP SHARING. 3613 02:15:07,840 --> 02:15:14,160 THAT WOULD BE GREAT. 3614 02:15:14,160 --> 02:15:14,880 WE'LL AGAIN TAKE QUESTIONS AT 3615 02:15:14,880 --> 02:15:19,320 THE END. 3616 02:15:19,320 --> 02:15:22,040 SO NEXT SPEAKER, I HAVE REALLY 3617 02:15:22,040 --> 02:15:24,040 NOTHING NICE TO SAY ABOUT IN WAY 3618 02:15:24,040 --> 02:15:27,720 OF INTRODUCTION. 3619 02:15:27,720 --> 02:15:28,960 SO I WILL JUST GET INTO IT 3620 02:15:28,960 --> 02:15:30,720 BECAUSE IT'S ME, AND I AM NOT 3621 02:15:30,720 --> 02:15:32,040 ABLE TO SHARE MY SCREEN FOR A 3622 02:15:32,040 --> 02:15:34,000 MINUTE. 3623 02:15:34,000 --> 02:15:35,480 DID YOU STOP SHARING, RAGHU? 3624 02:15:35,480 --> 02:15:35,960 >> YES. 3625 02:15:35,960 --> 02:15:38,360 >> ALL RIGHT, PERFECT. 3626 02:15:38,360 --> 02:15:41,560 THERE WE GO. 3627 02:15:41,560 --> 02:15:42,720 SO HOPEFULLY MY SLIDES ARE 3628 02:15:42,720 --> 02:15:46,360 COMING UP, AND AS I DO THAT, I 3629 02:15:46,360 --> 02:15:49,800 WOULD LIKE TO THANK THE 3630 02:15:49,800 --> 02:15:51,120 ORGANIZERS FOR -- ZORINA AND 3631 02:15:51,120 --> 02:15:53,920 SELEN AND ILSA AND BABAK AND 3632 02:15:53,920 --> 02:15:55,120 ANDREA FOR ALL THEIR EFFORTS IN 3633 02:15:55,120 --> 02:15:56,800 PUTTING THIS TOGETHER, AND FOR 3634 02:15:56,800 --> 02:15:58,680 THE INVITATION TO PARTICIPATE IN 3635 02:15:58,680 --> 02:16:01,400 THIS YEAR'S YET TO BE CHARTED. 3636 02:16:01,400 --> 02:16:03,080 IT BEEN A GREAT MEETING, REALLY 3637 02:16:03,080 --> 02:16:03,920 ENJOYED BEING ABLE TO 3638 02:16:03,920 --> 02:16:04,480 PARTICIPATE. 3639 02:16:04,480 --> 02:16:06,200 SO I WAS ASKED TO TALK ABOUT OUR 3640 02:16:06,200 --> 02:16:08,200 WORK ON THE ROLE THAT BACTERIAL 3641 02:16:08,200 --> 02:16:09,560 INFECTIONS PLAY IN AFFECTING 3642 02:16:09,560 --> 02:16:12,040 LYMPHATIC FUNCTION. 3643 02:16:12,040 --> 02:16:14,000 AND SO I'LL JUST HOP INTO THAT. 3644 02:16:14,000 --> 02:16:15,360 FIRST I HAVE NO CONFLICTS TO 3645 02:16:15,360 --> 02:16:17,760 DECLARE. 3646 02:16:17,760 --> 02:16:23,320 AND SO MY GROUP HAS LONG BEEN 3647 02:16:23,320 --> 02:16:24,800 INTERESTED IN THE COLLECTING 3648 02:16:24,800 --> 02:16:26,720 LYMPHATIC VASCULATURE AND THE 3649 02:16:26,720 --> 02:16:28,360 ROLE -- THE SPECIALIZED FEATURES 3650 02:16:28,360 --> 02:16:31,760 OF THOSE VESSELS PLAY IN DRIVING 3651 02:16:31,760 --> 02:16:35,480 LYMPHATIC FLOW, INCLUDING THOSE 3652 02:16:35,480 --> 02:16:36,120 INTRALUMINAL VALVES WE'VE HEARD 3653 02:16:36,120 --> 02:16:41,400 ABOUT EARLIER SWRELS AS WELE 3654 02:16:41,400 --> 02:16:43,920 LYMPH MUSCLE CELLS. 3655 02:16:43,920 --> 02:16:45,920 IN ORDER DO THAT IN MY LAB, WE 3656 02:16:45,920 --> 02:16:48,840 DO A LOT OF INTRAVITAL 3657 02:16:48,840 --> 02:16:49,640 MICROSCOPY WHERE WE'LL TAKE 3658 02:16:49,640 --> 02:16:51,160 ANIMALS AND PUT THEM DIRECTLY 3659 02:16:51,160 --> 02:16:52,160 UNDER THE MICROSCOPE, AND THIS 3660 02:16:52,160 --> 02:16:53,800 ALLOWS US TO FOLLOW ANY DISEASE 3661 02:16:53,800 --> 02:16:54,920 PROCESS LONGITUDINALLY OVER 3662 02:16:54,920 --> 02:16:59,600 TIME, AS WELL AS SEE HOW ANY 3663 02:16:59,600 --> 02:17:00,240 POTENTIAL EXPERIMENTAL 3664 02:17:00,240 --> 02:17:01,120 THERAPEUTIC INTERVENTION MIGHT 3665 02:17:01,120 --> 02:17:01,840 AFFECT THAT DISEASE PROCESS. 3666 02:17:01,840 --> 02:17:04,000 WE CAN ALSO LOOK ON SHORTER TIME 3667 02:17:04,000 --> 02:17:06,400 FRAMES AND LOOK AT MORE DYNAMIC 3668 02:17:06,400 --> 02:17:07,440 THINGS SUCH AS LYMPHATIC 3669 02:17:07,440 --> 02:17:08,440 PUMPING. 3670 02:17:08,440 --> 02:17:10,400 AND SO THIS WAS A TECHNIQUE 3671 02:17:10,400 --> 02:17:16,200 DEVELOPED IN MY LAB BY SHAN 3672 02:17:16,200 --> 02:17:19,720 LIAO, SHE NOW HAS HER OWN LAB AT 3673 02:17:19,720 --> 02:17:20,480 THE UNIVERSITY OF CALGARY DOING 3674 02:17:20,480 --> 02:17:21,760 LOTS OF INTERESTING WORK SO I 3675 02:17:21,760 --> 02:17:22,800 ENCOURAGE YOU TO CHECK OUT WHAT 3676 02:17:22,800 --> 02:17:24,120 SHE'S DOING AS WELL. 3677 02:17:24,120 --> 02:17:26,080 BUT SHAN DEVELOPED THIS. 3678 02:17:26,080 --> 02:17:28,160 THIS IS LEADING TO THE POPLITEAL 3679 02:17:28,160 --> 02:17:28,800 LYMPH NODE IN THE MOUSE BUT 3680 02:17:28,800 --> 02:17:30,240 BECAUSE SHE WAS DOING THIS IN 3681 02:17:30,240 --> 02:17:31,720 THE MOUSE NOW, IT OPENED UP ALL 3682 02:17:31,720 --> 02:17:33,400 THE MOLECULAR AND GENETIC MODELS 3683 02:17:33,400 --> 02:17:34,720 AVAILABLE IN MOUSE SYSTEMS TO BE 3684 02:17:34,720 --> 02:17:36,120 ABLE TO START TO THINK ABOUT AND 3685 02:17:36,120 --> 02:17:38,680 STUP DI HOW THIS MIGHT BE 3686 02:17:38,680 --> 02:17:40,880 REGULATED AT A MOLECULAR LEVEL. 3687 02:17:40,880 --> 02:17:42,480 IN SOME OF OUR WORK, WE'RE 3688 02:17:42,480 --> 02:17:45,520 REALLY INTERESTED IN SORT OF NOT 3689 02:17:45,520 --> 02:17:49,200 THINKING OF COLLECTING LYMPHATIC 3690 02:17:49,200 --> 02:17:50,640 VESSELS AS TUBES BECAUSE THEY 3691 02:17:50,640 --> 02:17:53,480 HAVE THESE VALVES WITH A TRACK 3692 02:17:53,480 --> 02:17:54,600 TILE UNIT AND THERE WILL BE 3693 02:17:54,600 --> 02:17:55,560 ANOTHER OFF THE SCREEN BUT 3694 02:17:55,560 --> 02:17:57,120 REALLY IT'S A LITTLE PUP . 3695 02:17:57,120 --> 02:17:58,880 SO THESE COLLECTING LYMPHATIC 3696 02:17:58,880 --> 02:18:00,400 VESSELS ARE REALLY A WHOLE BUNCH 3697 02:18:00,400 --> 02:18:02,080 OF THESE PUMPS ALL PUT IN 3698 02:18:02,080 --> 02:18:02,400 SERIES. 3699 02:18:02,400 --> 02:18:04,080 SO WE LIKE TO THINK ABOUT HOW 3700 02:18:04,080 --> 02:18:05,720 ALL THAT PUMPING OF THESE 3701 02:18:05,720 --> 02:18:07,800 INDIVIDUAL PUMPS HAS TO BE 3702 02:18:07,800 --> 02:18:10,440 COORDINATED IN ORDER TO GET 3703 02:18:10,440 --> 02:18:11,320 EFFICIENT FLOW. 3704 02:18:11,320 --> 02:18:12,280 I DON'T HAVE TIME TO TALK ABOUT 3705 02:18:12,280 --> 02:18:14,080 THAT TODAY, BUT THE WORK I WILL 3706 02:18:14,080 --> 02:18:15,720 TALK ABOUT IS SOME OF THE 3707 02:18:15,720 --> 02:18:16,280 DISEASE MODELS THAT WE'RE 3708 02:18:16,280 --> 02:18:18,400 INTERESTED IN, AND THE ONE I'LL 3709 02:18:18,400 --> 02:18:20,880 TALK ABOUT IS BACTERIAL 3710 02:18:20,880 --> 02:18:23,360 INFECTIONS. 3711 02:18:23,360 --> 02:18:24,720 SO THESE SKIN AND SOFT TISSUE 3712 02:18:24,720 --> 02:18:26,040 INFECTIONS ARE VERY COMMON IN 3713 02:18:26,040 --> 02:18:26,600 PATIENTS WITH LYMPHEDEMA. 3714 02:18:26,600 --> 02:18:29,120 SO LYMPHEDEMA, WE KNOW HAS THIS 3715 02:18:29,120 --> 02:18:31,400 IMPAIRMENT OF FLUID RETURN, BUT 3716 02:18:31,400 --> 02:18:33,280 THAT FLUID IS USUALLY ALSO 3717 02:18:33,280 --> 02:18:35,920 ENRICHED WITH ANTIGEN AND 3718 02:18:35,920 --> 02:18:37,560 ANTIGEN-PRESENTING CELLS, WHICH 3719 02:18:37,560 --> 02:18:38,000 GO TO LYMPH NODES. 3720 02:18:38,000 --> 02:18:40,960 AND THOSE ARE THEN DESIGNED TO 3721 02:18:40,960 --> 02:18:42,720 HELP INSTITUTE ROBUST IMMUNE 3722 02:18:42,720 --> 02:18:43,000 RESPONSES. 3723 02:18:43,000 --> 02:18:47,760 SO YOU HAVE BOTH FLUID STASIS 3724 02:18:47,760 --> 02:18:49,160 BUT ALSO -- THESE PATIENTS ARE 3725 02:18:49,160 --> 02:18:50,280 VERY, VERY PRONE TO GETTING 3726 02:18:50,280 --> 02:18:53,760 THESE SOFT TISSUE INFECTIONS. 3727 02:18:53,760 --> 02:18:55,520 THEY'RE VERY DIFFICULT TO TREAT, 3728 02:18:55,520 --> 02:18:56,720 THEY OFTEN END UP BEING 3729 02:18:56,720 --> 02:18:58,320 HOSPITALIZED TO GET IV 3730 02:18:58,320 --> 02:18:59,760 ANTIBIOTICS FOR TREATMENT, AND 3731 02:18:59,760 --> 02:19:01,480 THEY ALSO -- SOME PATIENTS 3732 02:19:01,480 --> 02:19:02,360 DEVELOP PATTERNS OF GETTING 3733 02:19:02,360 --> 02:19:03,840 THESE RECURRENT INFECTIONS SO 3734 02:19:03,840 --> 02:19:05,120 THEY BECOME BASICALLY FREQUENT 3735 02:19:05,120 --> 02:19:06,560 FLYERS GETTING THESE REPEATED 3736 02:19:06,560 --> 02:19:06,840 INFECTIONS. 3737 02:19:06,840 --> 02:19:10,920 SO IT'S WELL ESTABLISHED THAT 3738 02:19:10,920 --> 02:19:11,840 LYMPHEDEMA PATIENTS GET THESE 3739 02:19:11,840 --> 02:19:13,320 SKIN AND SOFT TISSUE INFECTIONS. 3740 02:19:13,320 --> 02:19:15,960 BUT THEN THERE'S OTHER GROUPS OF 3741 02:19:15,960 --> 02:19:20,960 PATIENTS THAT HAVE NO KNOWN 3742 02:19:20,960 --> 02:19:22,440 LYMPHATIC DYSFUNCTION BUT ALSO 3743 02:19:22,440 --> 02:19:24,280 GET THESE SSTIs. 3744 02:19:24,280 --> 02:19:25,520 SOME OF THOSE PATIENTS GO ON TO 3745 02:19:25,520 --> 02:19:26,880 START DEVELOPING THIS PATTERN OF 3746 02:19:26,880 --> 02:19:31,400 GETTING THESE REPEATED 3747 02:19:31,400 --> 02:19:32,080 INFECTIONS. 3748 02:19:32,080 --> 02:19:32,760 LOOKING LIKE LYMPHEDEMA 3749 02:19:32,760 --> 02:19:33,400 PATIENTS. 3750 02:19:33,400 --> 02:19:34,600 AND THERE'S ALSO DOCUMENTATION 3751 02:19:34,600 --> 02:19:36,360 IN THE LITERATURE THAT SOME 3752 02:19:36,360 --> 02:19:39,680 PATIENTS, AFTER AN INFECTION, 3753 02:19:39,680 --> 02:19:40,320 CAN DEVELOP LYMPHATIC 3754 02:19:40,320 --> 02:19:40,760 DYSFUNCTION. 3755 02:19:40,760 --> 02:19:44,080 THIS IS WORK FROM PETER 3756 02:19:44,080 --> 02:19:45,920 MORTIMER. 3757 02:19:45,920 --> 02:19:46,920 THERE'S ALSO -- PATIENTS THAT 3758 02:19:46,920 --> 02:19:49,240 HAVE REPEATED INFECTIONS CAN GO 3759 02:19:49,240 --> 02:19:59,520 ON TO DEVELOP LORNG TERM LONG TM 3760 02:19:59,520 --> 02:20:00,640 LYMPHEDEMA. 3761 02:20:00,640 --> 02:20:02,800 A YOUNG GIRL WAS OUT ON A 3762 02:20:02,800 --> 02:20:04,120 PLAYGROUND, GOT A CUT ON HER 3763 02:20:04,120 --> 02:20:10,040 LOWER LEG, IT GOT INNECTED D 3764 02:20:10,040 --> 02:20:11,160 AND EVER SINCE SHE'S HAD 3765 02:20:11,160 --> 02:20:12,360 LYMPHEDEMA IN THAT LOWER LIMB. 3766 02:20:12,360 --> 02:20:13,360 SO INFECTION SEEMS TO ACTUALLY 3767 02:20:13,360 --> 02:20:15,400 BE A SOURCE AND CAUSE 3768 02:20:15,400 --> 02:20:16,400 LYMPHEDEMA, WHICH THEN, OF 3769 02:20:16,400 --> 02:20:17,640 COURSE, IF YOU COMPLETE THAT 3770 02:20:17,640 --> 02:20:19,040 CIRCLE, MAKES THESE PATIENTS 3771 02:20:19,040 --> 02:20:20,480 MORE PRONE TO GETTING REPEATED 3772 02:20:20,480 --> 02:20:21,400 INFECTIONS. 3773 02:20:21,400 --> 02:20:22,400 SO REALLY THE QUESTION WE WANTED 3774 02:20:22,400 --> 02:20:25,560 TO ASK IS, HOW ARE THESE 3775 02:20:25,560 --> 02:20:26,280 BACTERIAL INFECTIONS AFFECT 3776 02:20:26,280 --> 02:20:27,680 BEING THE FUNCTION OF OUR 3777 02:20:27,680 --> 02:20:28,320 LYMPHATIC SYSTEM? 3778 02:20:28,320 --> 02:20:30,080 SO THAT WAS A PROJECT TAKEN ON 3779 02:20:30,080 --> 02:20:31,920 BY DENNIS JONES WHEN HE WAS A 3780 02:20:31,920 --> 02:20:32,840 POSTDOCTORAL FELLOW IN OUR 3781 02:20:32,840 --> 02:20:33,840 GROUP. 3782 02:20:33,840 --> 02:20:36,120 DENNIS NOW HAS HIS OWN LAB THAT 3783 02:20:36,120 --> 02:20:37,600 HE'S ESTABLISHED AT BOSTON 3784 02:20:37,600 --> 02:20:38,480 UNIVERSITY AND HE'S ALSO DOING 3785 02:20:38,480 --> 02:20:39,680 VERY INTERESTING WORK SO I 3786 02:20:39,680 --> 02:20:40,560 ENCOURAGE YOU TO CHECK OUT WHAT 3787 02:20:40,560 --> 02:20:41,920 HE'S DOING AS WELL. 3788 02:20:41,920 --> 02:20:44,160 SO WHAT DENNIS DID IS HE TOOK 3789 02:20:44,160 --> 02:20:45,800 ONE OF THE MORE COMMON BACTERIAL 3790 02:20:45,800 --> 02:20:47,600 STRAINS THAT ARE CAUSING THESE 3791 02:20:47,600 --> 02:20:48,920 SSTIs, AT LEAST IN THE U.S., 3792 02:20:48,920 --> 02:20:51,320 WHICH IS STAPHYLOCOCCAL AUREUS, 3793 02:20:51,320 --> 02:20:55,280 AND SPECIFICALLY HE FOCUSED ON 3794 02:20:55,280 --> 02:20:56,720 METHICILLIN RESISTANT STRAIN, SO 3795 02:20:56,720 --> 02:20:57,200 MRSA. 3796 02:20:57,200 --> 02:20:59,640 SO DENNIS USED THAT MODEL THAT 3797 02:20:59,640 --> 02:21:01,680 SHAN HAD AND INFECTED IT WITH 3798 02:21:01,680 --> 02:21:03,320 MRSA, SO YOU CAN SEE OUR 3799 02:21:03,320 --> 02:21:06,120 UNINFECTED CONTROL ANIMAL HAVING 3800 02:21:06,120 --> 02:21:07,320 NICE STRONG CONTRACTIONS AND 3801 02:21:07,320 --> 02:21:08,840 WHEN DENNIS INFECTED WITH THE 3802 02:21:08,840 --> 02:21:10,160 MRSA, HE LOST THOSE STRONG 3803 02:21:10,160 --> 02:21:11,320 CONTRACTIONS. 3804 02:21:11,320 --> 02:21:12,960 SO THIS IS A NICE MODEL TO BE 3805 02:21:12,960 --> 02:21:15,360 ABLE TO WATCH THE WALL MOTION, 3806 02:21:15,360 --> 02:21:17,360 BUT IT'S HARD TO REALLY ASSESS 3807 02:21:17,360 --> 02:21:18,440 OUT WHAT'S HAPPENING WITH LYMPH 3808 02:21:18,440 --> 02:21:21,280 FLOW. 3809 02:21:21,280 --> 02:21:26,760 SO IN COLLABORATION WITH AN 3810 02:21:26,760 --> 02:21:28,960 EXPERT IN THIS HE DEVELOPED A 3811 02:21:28,960 --> 02:21:31,240 TECHNIQUE THAT ALLOWS US TO 3812 02:21:31,240 --> 02:21:36,080 MEASURE LYMPH FLOW, WHEN WE 3813 02:21:36,080 --> 02:21:39,040 INFECT WITH MRSA, WE LOSE THAT 3814 02:21:39,040 --> 02:21:40,320 PULSATILITY AND THE VELOCITY OF 3815 02:21:40,320 --> 02:21:42,520 THE FLOW IS BASICALLY SITTING AT 3816 02:21:42,520 --> 02:21:42,880 ZERO. 3817 02:21:42,880 --> 02:21:47,960 SO MRSA INFORECAST, WE E 3818 02:21:47,960 --> 02:21:49,040 ABILITY OF THE VESSELS TO 3819 02:21:49,040 --> 02:21:50,680 CONTRACT AND WE LOSE LYMPH FLOW. 3820 02:21:50,680 --> 02:21:51,680 SO WHAT'S HAPPENING? 3821 02:21:51,680 --> 02:21:52,840 ONE OF THE CRITICAL OBSERVATIONS 3822 02:21:52,840 --> 02:21:54,920 DENNIS MADE, AND JUST FOR 3823 02:21:54,920 --> 02:21:55,680 REFERENCE, WE MEASURE THE SORT 3824 02:21:55,680 --> 02:21:57,680 OF STRENGTH OF CONTRACTION USING 3825 02:21:57,680 --> 02:21:59,120 EJECTION FRACTION WHICH IS JUST 3826 02:21:59,120 --> 02:22:00,840 A THEORETICAL VOLUME THAT WOULD 3827 02:22:00,840 --> 02:22:04,240 GET SQUEEZED OUT WITH A SINGLE 3828 02:22:04,240 --> 02:22:05,360 CONTRACTION, WHAT DENNIS 3829 02:22:05,360 --> 02:22:06,760 OBSERVED WAS THAT THIS 3830 02:22:06,760 --> 02:22:08,320 IMPAIRMENT IN PUMPING WAS 3831 02:22:08,320 --> 02:22:11,280 BASICALLY PERMANENT. 3832 02:22:11,280 --> 02:22:12,520 EVEN LONG AFTER THE BACTERIA HAD 3833 02:22:12,520 --> 02:22:15,480 BEEN CLEARED. 3834 02:22:15,480 --> 02:22:16,880 THE MICE CLEAR THE BACTERIA 3835 02:22:16,880 --> 02:22:18,880 NATURALLY BY ABOUT DAY 30, SO 3836 02:22:18,880 --> 02:22:22,280 THIS IS JUST LOOKING WITH 3837 02:22:22,280 --> 02:22:23,480 FORMATION ASSAYS, TRYING TO FIND 3838 02:22:23,480 --> 02:22:25,600 THE BUGS AT DAY 30, WE CAN'T SEE 3839 02:22:25,600 --> 02:22:28,120 THEM, WHERE AT DAY 4 IF WE TRIED 3840 02:22:28,120 --> 02:22:29,640 TO DO PCR FOR GENETIC MATERIAL 3841 02:22:29,640 --> 02:22:31,200 FROM THE BACTERIA AT DAY 30, WE 3842 02:22:31,200 --> 02:22:32,400 COULDN'T FIND IT. 3843 02:22:32,400 --> 02:22:33,840 SO THE BUGS ARE CLEARED AND WE 3844 02:22:33,840 --> 02:22:35,280 SEE THIS PERMANENT IMPAIRMENT. 3845 02:22:35,280 --> 02:22:39,520 AND THIS WAS DIFFERENT FROM WORK 3846 02:22:39,520 --> 02:22:40,760 SHAN HAD DONE WHEN SHE WAS IN MY 3847 02:22:40,760 --> 02:22:42,400 GROUP WHEN SHE WAS STUDYING 3848 02:22:42,400 --> 02:22:45,280 STERILE INFLAMMATION USING -- 3849 02:22:45,280 --> 02:22:46,480 AND SKIN PAINTING. 3850 02:22:46,480 --> 02:22:48,760 SO WHEN SHE CREATED STERILE 3851 02:22:48,760 --> 02:22:50,120 INFLAMMATION, SHE HAD BONE 3852 02:22:50,120 --> 02:22:53,520 MARROW DERIVED CELLS THAT WERE 3853 02:22:53,520 --> 02:22:56,560 PRODUCING NITRIC OXIDE THROUGH 3854 02:22:56,560 --> 02:22:59,160 INOS AND THEY BASICALLY CAUSED 3855 02:22:59,160 --> 02:23:00,440 THE PUMPING TO STOP AND VESSELS 3856 02:23:00,440 --> 02:23:01,200 TO DILATE. 3857 02:23:01,200 --> 02:23:04,040 AS THE INFLAMMATION RESOLVED, 3858 02:23:04,040 --> 02:23:06,960 SHAN FOUND THAT EJECTION 3859 02:23:06,960 --> 02:23:07,840 FRACTION AND STRENGTH OF THE 3860 02:23:07,840 --> 02:23:09,440 PUMPING WOULD COME BACK. 3861 02:23:09,440 --> 02:23:11,240 SO DENNIS SAID MAYBE THESE 3862 02:23:11,240 --> 02:23:12,160 BACTERIAL INFECTIONS ARE CAUSING 3863 02:23:12,160 --> 02:23:13,760 A VERY PROLONGED INFLAMMATORY 3864 02:23:13,760 --> 02:23:15,400 RESPONSE SO WE DID PROTEOMICS TO 3865 02:23:15,400 --> 02:23:16,760 SEE WHAT ALL THE INFLAMMATORY 3866 02:23:16,760 --> 02:23:17,440 CYTOKINES WERE DOING. 3867 02:23:17,440 --> 02:23:20,440 SO AT DAY 4, WE CAN SEE NOT 3868 02:23:20,440 --> 02:23:21,200 SURPRISINGLY A LOT OF 3869 02:23:21,200 --> 02:23:22,400 INFLAMMATION IN THE TISSUE BUT 3870 02:23:22,400 --> 02:23:24,200 BY DAY 60, THAT'S ALL PRETTY 3871 02:23:24,200 --> 02:23:24,640 MUCH RESOLVED. 3872 02:23:24,640 --> 02:23:27,160 BUT YET WE STILL SEE THIS NEAR 3873 02:23:27,160 --> 02:23:27,800 PERMANENT IMPAIRMENT IN 3874 02:23:27,800 --> 02:23:28,560 CONTRACTION. 3875 02:23:28,560 --> 02:23:29,920 SO WHAT'S HAPPENING? 3876 02:23:29,920 --> 02:23:31,640 SO DENNIS THOUGHT, WELL, OKAY, 3877 02:23:31,640 --> 02:23:33,080 WE KNOW LYMPHATIC MUSCLE IS 3878 02:23:33,080 --> 02:23:34,200 REALLY CRITICAL FOR THIS 3879 02:23:34,200 --> 02:23:35,400 PUMPING, LET'S SEE WHAT'S 3880 02:23:35,400 --> 02:23:36,720 HAPPENING WITH LYMPHATIC MUSCLE 3881 02:23:36,720 --> 02:23:37,200 CELL. 3882 02:23:37,200 --> 02:23:38,160 AND THIS WAS REALLY SURPRISING 3883 02:23:38,160 --> 02:23:40,080 TO US, BECAUSE THIS IS JUST TWO 3884 02:23:40,080 --> 02:23:41,240 WAYS LOOKING AT LYMPHATIC 3885 02:23:41,240 --> 02:23:41,480 MUSCLE. 3886 02:23:41,480 --> 02:23:43,800 CAN YOU SEE AFTER THE BACTERIAL 3887 02:23:43,800 --> 02:23:44,640 INFECTIONS, WE'VE LOST COVERAGE 3888 02:23:44,640 --> 02:23:47,840 OF OUR LYMPHATIC VESSEL. 3889 02:23:47,840 --> 02:23:49,040 THE MORPHOLOGY OF THE LYMPHATIC 3890 02:23:49,040 --> 02:23:50,440 MUSCLE CELLS LOOK DIFFERENT, AND 3891 02:23:50,440 --> 02:23:52,480 THEIR ORGANIZATION IS VERY 3892 02:23:52,480 --> 02:23:53,120 ABERRANT. 3893 02:23:53,120 --> 02:23:55,120 THIS IS TRUE AT 4 DAYS, 30 DAYS 3894 02:23:55,120 --> 02:23:57,280 AND EVEN OUT 260 DAYS AFTER 3895 02:23:57,280 --> 02:23:58,600 THESE MRSA INFECTIONS. 3896 02:23:58,600 --> 02:24:00,160 DENNIS ACTUALLY MEASURED FLOW 3897 02:24:00,160 --> 02:24:02,040 OUT AT 260 DAYS AND ALSO SHOWED 3898 02:24:02,040 --> 02:24:04,880 IT WAS STILL IMPAIRED. 3899 02:24:04,880 --> 02:24:06,520 SO THE MRSA INFECTION IS DOING 3900 02:24:06,520 --> 02:24:09,800 SOMETHING TO OUR LYMPHATIC MULLS 3901 02:24:09,800 --> 02:24:12,440 MUSSEL CELLS. 3902 02:24:12,440 --> 02:24:13,640 MUSCLE CELLS. 3903 02:24:13,640 --> 02:24:16,640 HE TOOK THEM, GREW THEM IN 3904 02:24:16,640 --> 02:24:18,920 CULTURE, DID A CELL VIABILITY 3905 02:24:18,920 --> 02:24:20,360 ASSAY AND BASICALLY SHOWED THE 3906 02:24:20,360 --> 02:24:22,520 MRSA MEDIUM WAS KILLING 3907 02:24:22,520 --> 02:24:24,480 LYMPHATIC MUSCLE CELLS. 3908 02:24:24,480 --> 02:24:25,840 SO FIRST WE WANT TO KNOW WHAT'S 3909 02:24:25,840 --> 02:24:27,520 IN THE MEDIA, SO WE TOOK A 3910 02:24:27,520 --> 02:24:28,640 PROTEOMIC APPROACH, WE PROBABLY 3911 02:24:28,640 --> 02:24:29,760 SHOULD HAVE FIGURED THIS OUT 3912 02:24:29,760 --> 02:24:32,560 BEFORE WE DID THIS BUT NOT 3913 02:24:32,560 --> 02:24:34,120 SURPRISINGLY, YOU FIND A LOT OF 3914 02:24:34,120 --> 02:24:35,560 BACTERIAL TOXINS IN THAT 3915 02:24:35,560 --> 02:24:36,200 CONDITIONED MEDIA. 3916 02:24:36,200 --> 02:24:37,520 FORTUNATELY FOR US, MANY OF 3917 02:24:37,520 --> 02:24:39,160 THOSE TOXINS WERE CONTROLLED BY 3918 02:24:39,160 --> 02:24:41,720 A SINGLE GENETIC ELEMENT IN THE 3919 02:24:41,720 --> 02:24:44,560 MRSA GENOME CALLED THE ACCESSORY 3920 02:24:44,560 --> 02:24:46,840 GENE REGULATOR, THE AGR. 3921 02:24:46,840 --> 02:24:49,240 THROUGH A VERY GENEROUS 3922 02:24:49,240 --> 02:24:52,160 COLLABORATOR WHO'S AT THE NIH 3923 02:24:52,160 --> 02:24:54,640 AND NIAID, MICHAEL OTTO, HE HAD 3924 02:24:54,640 --> 02:24:57,240 MADE MRSAs MUTANT FOR THE AGR, 3925 02:24:57,240 --> 02:24:59,280 SO HE GENEROUSLY PROVIDED THEM 3926 02:24:59,280 --> 02:25:02,320 TO US, SO DENNIS THEN TOOK 3927 02:25:02,320 --> 02:25:04,360 CONDITIONED MEDIA OFF AGR 3928 02:25:04,360 --> 02:25:06,600 MUTANTS, PUT THEM ON MUSCLE CELL 3929 02:25:06,600 --> 02:25:08,160 CULTURES AND SHOWED THE CELL 3930 02:25:08,160 --> 02:25:09,240 VIABILITY WAS MAINTAINED. 3931 02:25:09,240 --> 02:25:10,760 SO HOW ARE THE CELLS -- HOW ARE 3932 02:25:10,760 --> 02:25:14,000 THESE TOXINS KILLING CELLS? 3933 02:25:14,000 --> 02:25:20,240 WELL, A LOT OF THEM ARE -- THEY 3934 02:25:20,240 --> 02:25:23,440 CAUSE CELL LYSIS, SO WITH WILD 3935 02:25:23,440 --> 02:25:25,280 TYPE MRSA CONDITIONED MEDIA, WE 3936 02:25:25,280 --> 02:25:28,160 SEE A LOT OF CELL LYSIS WHICH 3937 02:25:28,160 --> 02:25:29,040 DISAPPEARS WITH THE AGR 3938 02:25:29,040 --> 02:25:29,680 CONDITIONED MEDIA. 3939 02:25:29,680 --> 02:25:31,280 THAT THEN TRANSLATED INTO IN 3940 02:25:31,280 --> 02:25:32,560 VIVO EXPERIMENTS WHERE IF WE 3941 02:25:32,560 --> 02:25:34,840 INFECTED WITH AGR MUTANT 3942 02:25:34,840 --> 02:25:36,400 BACTERIA, WE DIDN'T LOSE THAT 3943 02:25:36,400 --> 02:25:37,720 LYMPHATIC MUSCLE CELL COVERAGE 3944 02:25:37,720 --> 02:25:40,040 COMPARED TO OUR WILD TYPE MRSA. 3945 02:25:40,040 --> 02:25:44,160 AND ALSO THEN LOOKING IN VIVO, 3946 02:25:44,160 --> 02:25:46,440 PUMPING WAS MAINTAINED WITH AGR 3947 02:25:46,440 --> 02:25:50,240 MUTANT INFECTIONS. 3948 02:25:50,240 --> 02:25:52,240 SO IT SEEMS LIKE SOME THINGS 3949 02:25:52,240 --> 02:25:55,120 CONTROLLED BY THE AGR ARE 3950 02:25:55,120 --> 02:25:55,720 CAUSING LYMPHATIC MUSCLE CELL 3951 02:25:55,720 --> 02:25:57,080 DEATH AND IMPAIRING THE 3952 02:25:57,080 --> 02:25:59,280 LYMPHATIC PUMPING. 3953 02:25:59,280 --> 02:26:00,840 CAN WE ISOLATE ANY INDIVIDUAL 3954 02:26:00,840 --> 02:26:01,960 TOXIN THAT'S RESPONSIBLE FOR 3955 02:26:01,960 --> 02:26:03,080 THIS? 3956 02:26:03,080 --> 02:26:06,640 SO WE WENT BACK INTO OUR 3957 02:26:06,640 --> 02:26:08,400 LYMPHATIC MUSCLE CELL CULTURES 3958 02:26:08,400 --> 02:26:10,600 AND TOO MANY SOME OF THESE 3959 02:26:10,600 --> 02:26:13,760 TOXINS WE KNOW ARE IN THERE AND 3960 02:26:13,760 --> 02:26:14,840 JUST TOOK -- MEDIA AND STARTED 3961 02:26:14,840 --> 02:26:20,160 ADDING IN TOX IBS UP TOXI. 3962 02:26:20,160 --> 02:26:24,400 CAN YOU CAN SEE A LITTLE BIT OL 3963 02:26:24,400 --> 02:26:29,760 LYSIS IN THE RED AND BLACK, AND 3964 02:26:29,760 --> 02:26:31,560 THIS VERY POTENT AT CAUSING CELL 3965 02:26:31,560 --> 02:26:32,400 LYSIS. 3966 02:26:32,400 --> 02:26:33,920 HOWEVER WHEN WE DID THE REVERSE 3967 02:26:33,920 --> 02:26:35,520 EXPERIMENT WHERE WE TOOK THE 3968 02:26:35,520 --> 02:26:36,480 CONDITIONED MEDIA FROM BUGS THAT 3969 02:26:36,480 --> 02:26:38,360 JUST HAD A SINGLE TOXIN KNOCKED 3970 02:26:38,360 --> 02:26:41,000 OUT, IN THIS CASE, THE ALPHA 3971 02:26:41,000 --> 02:26:43,120 TOXIN AND THE DELTA TOXIN AND 3972 02:26:43,120 --> 02:26:46,960 EVEN THAT POTENT -- ALPHA, WE 3973 02:26:46,960 --> 02:26:50,560 DON'T SEE THE COMPLETE 3974 02:26:50,560 --> 02:26:52,560 RESUMPTION OF CELL VIABILITY 3975 02:26:52,560 --> 02:26:54,080 WITH IT JUST KNOCKING OUT 3976 02:26:54,080 --> 02:26:54,880 INDIVIDUAL TOXINS. 3977 02:26:54,880 --> 02:26:56,280 SO THIS WAS TELLING US THAT IT'S 3978 02:26:56,280 --> 02:26:57,840 NOT AN INDIVIDUAL TOXIN BUT 3979 02:26:57,840 --> 02:27:00,560 LIKELY THE COLLECTIVE EFFECT OF 3980 02:27:00,560 --> 02:27:06,200 ALL THESE TOXINS AND ALL THESE 3981 02:27:06,200 --> 02:27:08,480 PORE FRIN FORMING TOXINS PLAY 3982 02:27:08,480 --> 02:27:09,920 AGO ROLE IN LYMPHATIC MUSCLE 3983 02:27:09,920 --> 02:27:10,560 CELL. 3984 02:27:10,560 --> 02:27:17,520 IN VIVO TAKE THE OTHER QUET 3985 02:27:17,520 --> 02:27:19,720 FREQUENTLY IS, IS THIS REALLY 3986 02:27:19,720 --> 02:27:21,360 JUST A LYMPHATIC MUSCLE 3987 02:27:21,360 --> 02:27:23,680 CELL-SPECIFIC EFFECT? 3988 02:27:23,680 --> 02:27:25,600 AND SO THE APPROACH WE TOOK WAS 3989 02:27:25,600 --> 02:27:27,640 TO THEN CULTURE IN LYMPHATIC 3990 02:27:27,640 --> 02:27:28,280 ENDOTHELIAL CELLS. 3991 02:27:28,280 --> 02:27:30,720 THESE ARE SMOOTH MUSCLE CELLS 3992 02:27:30,720 --> 02:27:32,600 FROM BLOOD VESSELS IN THE HOUSE 3993 02:27:32,600 --> 02:27:33,800 AND HUMAN. 3994 02:27:33,800 --> 02:27:35,880 WE ALSO DID THIS WITH BLOOD 3995 02:27:35,880 --> 02:27:36,880 ENDOTHELIAL CELLS, AND WHEN WE 3996 02:27:36,880 --> 02:27:39,320 GIVE THE WILD TYPE CONDITIONED 3997 02:27:39,320 --> 02:27:40,320 MEDIA, MRSA CONDITIONED MEDIA, 3998 02:27:40,320 --> 02:27:42,720 WE DID SEE THAT SAME CELL DEATH 3999 02:27:42,720 --> 02:27:44,080 NOT PRESENT WITH THE AGR. 4000 02:27:44,080 --> 02:27:46,080 SO IT'S NOT SPECIFIC TO 4001 02:27:46,080 --> 02:27:46,720 LYMPHATIC MUSCLE CELLS. 4002 02:27:46,720 --> 02:27:49,000 I'LL SAY IF WE LOOK EARLY IN 4003 02:27:49,000 --> 02:27:49,600 INFECTION, ONE DAY, TWO DAYS 4004 02:27:49,600 --> 02:27:52,000 AFTER A MRSA INFORECAST, WHAT WE 4005 02:27:52,000 --> 02:27:53,400 OBSERVE IS HEMORRHAGE, 4006 02:27:53,400 --> 02:27:55,160 SUGGESTING THAT THE BLOOD 4007 02:27:55,160 --> 02:27:56,280 ENDOTHELIAL CELL LAYER HAS BEEN 4008 02:27:56,280 --> 02:27:57,080 BREACHED. 4009 02:27:57,080 --> 02:27:58,760 WE SEE LOSS OF VASCULAR SMOOTH 4010 02:27:58,760 --> 02:27:59,400 MUSCLE CELLS. 4011 02:27:59,400 --> 02:28:04,640 AND WE SEE -- IF WE DO 4012 02:28:04,640 --> 02:28:05,760 LYMPHANGIOGRAPHY, IF WE FILL 4013 02:28:05,760 --> 02:28:10,440 THOSE VESSELS WITH THE 4014 02:28:10,440 --> 02:28:12,600 LYMPHANGIOGRAPHY DYE, WE'LL SEE 4015 02:28:12,600 --> 02:28:14,320 IT LEAKING OUT SUGGESTING 4016 02:28:14,320 --> 02:28:15,440 LYMPHATIC ENDOTHELIAL CELLS HAVE 4017 02:28:15,440 --> 02:28:16,280 ALSO BEEN DAMAGED. 4018 02:28:16,280 --> 02:28:17,640 HOWEVER, IF WE LOOK AT DAY 30, 4019 02:28:17,640 --> 02:28:19,200 WE STOP TO SEE THAT LYMPHATIC 4020 02:28:19,200 --> 02:28:20,840 LEAK, WE SEE SMOOTH MUSCLE 4021 02:28:20,840 --> 02:28:22,840 COVERAGE BACK INTACT ON THE 4022 02:28:22,840 --> 02:28:24,360 BLOOD VESSELS AND WE DON'T SEE 4023 02:28:24,360 --> 02:28:24,800 HEMORRHAGE. 4024 02:28:24,800 --> 02:28:26,360 SO ALL THOSE CELL TYPES ARE ABLE 4025 02:28:26,360 --> 02:28:27,560 TO REPAIR THEMSELVES AND REPAIR 4026 02:28:27,560 --> 02:28:30,440 THE VESSELS, BUT THE LYMPHATIC 4027 02:28:30,440 --> 02:28:31,400 MUSCLE CELLS DON'T SEEM TO BE 4028 02:28:31,400 --> 02:28:32,840 ABLE TO HAVE THAT REGENERATIVE 4029 02:28:32,840 --> 02:28:34,800 CAPACITY TO REINVEST THOSE 4030 02:28:34,800 --> 02:28:37,600 COLLECTING LYMPHATIC VESSELS. 4031 02:28:37,600 --> 02:28:40,040 THE OTHER QUESTION WE GET IS IS 4032 02:28:40,040 --> 02:28:41,920 THIS ONLY MRSA THAT CAUSES THIS. 4033 02:28:41,920 --> 02:28:43,120 SO WE TRIED WITH ANOTHER BUG, AT 4034 02:28:43,120 --> 02:28:45,800 LEAST IN THE U.S., THAT CAUSES A 4035 02:28:45,800 --> 02:28:49,320 LOT OF CELLULITIS AND SSTIs, 4036 02:28:49,320 --> 02:28:52,920 WHICH IS STREP PYOGENES, AND 4037 02:28:52,920 --> 02:28:56,040 SIMILARLY WITH EITHER LOW OR 4038 02:28:56,040 --> 02:29:02,280 HIGH TITER INFECTIONS W WE SEE- 4039 02:29:02,280 --> 02:29:05,040 PARALYSIS OCCURS AND SIMILARLY 4040 02:29:05,040 --> 02:29:07,680 AT DAY 30 WE LOSE THAT LYMPHATIC 4041 02:29:07,680 --> 02:29:12,720 CONTRACTION PERMANENTLY. 4042 02:29:12,720 --> 02:29:16,040 WE SEE LOSS OF LYMPHATIC 4043 02:29:16,040 --> 02:29:16,320 COVERAGE. 4044 02:29:16,320 --> 02:29:18,320 SO REALLY WHERE I SEE SORT OF 4045 02:29:18,320 --> 02:29:20,200 QUESTIONS AND THINGS, THE GAPS 4046 02:29:20,200 --> 02:29:21,760 AND OPPORTUNITIES TO EXPLORE IN 4047 02:29:21,760 --> 02:29:23,880 THIS SPACE, IS FIRST MAIN 4048 02:29:23,880 --> 02:29:26,480 DRIVING QUESTION FOR US IS, WHY 4049 02:29:26,480 --> 02:29:27,800 LYMPHATIC MUSCLE CELLS DON'T 4050 02:29:27,800 --> 02:29:30,000 SEEM TO REGENERATE TO REINVEST 4051 02:29:30,000 --> 02:29:31,800 THESE LYMPHATIC VESSELS AFTER 4052 02:29:31,800 --> 02:29:33,000 INFECTION, AND THE COROLLARY TO 4053 02:29:33,000 --> 02:29:34,080 THAT QUESTION IS, OF COURSE, IS 4054 02:29:34,080 --> 02:29:37,160 IT POSSIBLE TO INDUCE LYMPHATIC 4055 02:29:37,160 --> 02:29:38,520 MUSCLE CELERY GENERATION TO 4056 02:29:38,520 --> 02:29:41,240 CAUSE THE COVERAGE AND REPAIR 4057 02:29:41,240 --> 02:29:44,600 THESE LYMPHATIC VESSELS TO TRY 4058 02:29:44,600 --> 02:29:46,280 TO RESTORE -- TO PREVENT THESE 4059 02:29:46,280 --> 02:29:47,520 CYCLES OF RECURRENT INFECTIONS. 4060 02:29:47,520 --> 02:29:49,640 TO DO THAT, I'VE BEEN TOLD BY A 4061 02:29:49,640 --> 02:29:50,920 VERY SMART SCIENTIST THAT TO 4062 02:29:50,920 --> 02:29:51,520 UNDERSTAND DISEASE, OFTEN WE 4063 02:29:51,520 --> 02:29:53,600 NEED TO UNDERSTAND DEVELOPMENT. 4064 02:29:53,600 --> 02:29:56,080 AND WE DON'T REALLY UNDERSTAND 4065 02:29:56,080 --> 02:29:58,120 WHERE LYMPHATIC MUSCLE CELLS 4066 02:29:58,120 --> 02:29:59,920 COME FROM IN DEVELOPMENT. 4067 02:29:59,920 --> 02:30:01,640 AND IF WE DID, WE MIGHT BE ABLE 4068 02:30:01,640 --> 02:30:03,320 TO THEN USE THAT INFORMATION TO 4069 02:30:03,320 --> 02:30:05,600 FIGURE OUT HOW TO CAUSE 4070 02:30:05,600 --> 02:30:10,960 LYMPHATIC MUSCLE CELERY GROWTH H 4071 02:30:10,960 --> 02:30:11,800 AND REGENERATION. 4072 02:30:11,800 --> 02:30:12,920 SO THIS IS A HUGE KNOWLEDGE GAP 4073 02:30:12,920 --> 02:30:16,720 IN OUR FIELD AND THIS COULD 4074 02:30:16,720 --> 02:30:18,600 REALLY HELP DEVELOPING BOTH 4075 02:30:18,600 --> 02:30:19,840 THERAPEUTICS AND BASIC 4076 02:30:19,840 --> 02:30:20,960 UNDERSTANDING OF OUR LYMPHATIC 4077 02:30:20,960 --> 02:30:21,240 SYSTEM. 4078 02:30:21,240 --> 02:30:22,800 SORT OF IN A DIFFERENT REALM, 4079 02:30:22,800 --> 02:30:25,240 I'VE BEEN YOU BE TALKING ABOUT 4080 02:30:25,240 --> 02:30:26,440 THESE BACTERIAL INFECTIONS BUT 4081 02:30:26,440 --> 02:30:27,760 WORLDWIDE THE MOST COMMON CAUSE 4082 02:30:27,760 --> 02:30:29,960 OF DEERM IS AN INFECTION WITH 4083 02:30:29,960 --> 02:30:36,680 THE PARASITE, THE FILARIAL 4084 02:30:36,680 --> 02:30:37,760 PAIROCYTES. 4085 02:30:37,760 --> 02:30:42,960 THEY ALSO HAVE WOLBACHIA, 4086 02:30:42,960 --> 02:30:45,720 WHETHER THAT ITSELF COULD CAUSE 4087 02:30:45,720 --> 02:30:47,560 LOSS OF LYMPHATIC MUSCLE CELL 4088 02:30:47,560 --> 02:30:48,640 COVERAGE OR THE PARASITES 4089 02:30:48,640 --> 02:30:49,400 THEMSELVES CAN. 4090 02:30:49,400 --> 02:30:50,480 BECAUSE THOSE PATIENTS CAN CLEAR 4091 02:30:50,480 --> 02:30:53,280 THE PARASITES WITH TREATMENT, 4092 02:30:53,280 --> 02:30:54,840 BUT YET THEY ALWAYS HAVE THAT 4093 02:30:54,840 --> 02:30:56,040 PERMANENT LYMPHEDEMA AND 4094 02:30:56,040 --> 02:30:57,040 PERMANENT LYMPHATIC IMPAIRMENT. 4095 02:30:57,040 --> 02:30:58,000 WITH THAT, I WANT TO THANK 4096 02:30:58,000 --> 02:30:59,000 PEOPLE THAT DID THE WORK. 4097 02:30:59,000 --> 02:31:00,480 THIS IS MY CURRENT GROUP, REALLY 4098 02:31:00,480 --> 02:31:01,840 THE WORK I SHOWED TODAY WAS 4099 02:31:01,840 --> 02:31:03,560 SHOWN BY DENNIS JONES WHO HAS 4100 02:31:03,560 --> 02:31:05,960 HIS OWN LAB AT BOSTON UNIVERSITY 4101 02:31:05,960 --> 02:31:09,200 AND FOUNDATIONAL WORK FROM SHAN 4102 02:31:09,200 --> 02:31:11,600 LIAO AT UNIVERSITY OF CALGARY. 4103 02:31:11,600 --> 02:31:15,560 FUNDING SOURCES FROM LE&RN AND 4104 02:31:15,560 --> 02:31:17,600 THE LYMPHEDEMA FOUNDATION, OF 4105 02:31:17,600 --> 02:31:19,320 COURSE NIH, THE MASSACHUSETTS 4106 02:31:19,320 --> 02:31:21,400 GENERAL HOSPITAL AND THE RULLO 4107 02:31:21,400 --> 02:31:22,520 FAMILY FOR SUPPORTING MY LAB. 4108 02:31:22,520 --> 02:31:23,840 SO WITH THAT, I THANK YOU AND 4109 02:31:23,840 --> 02:31:25,280 I'LL STOP SHARING. 4110 02:31:25,280 --> 02:31:29,320 AND NOW WE'RE MOVING INTO THE 4111 02:31:29,320 --> 02:31:30,960 QUESTION AND ANSWER PERIOD FROM 4112 02:31:30,960 --> 02:31:32,600 ALL THE SPEAKERS STARTING FROM 4113 02:31:32,600 --> 02:31:34,680 STAN ROCKSON, SO I ENCOURAGE YOU 4114 02:31:34,680 --> 02:31:36,280 TO KEEP FILLING IN THE Q & A, 4115 02:31:36,280 --> 02:31:38,720 AND I SEE SELEN HAS HER HAND 4116 02:31:38,720 --> 02:31:40,720 RAISED, SO I'M GOING TO ASK HER 4117 02:31:40,720 --> 02:31:42,920 TO LEAD THE FIRST QUESTION. 4118 02:31:42,920 --> 02:31:44,480 >> THANK YOU, TIM. 4119 02:31:44,480 --> 02:31:45,640 THIS WAS ANOTHER GREAT SESSION. 4120 02:31:45,640 --> 02:31:48,440 THANK YOU SO MUCH TO EVERYONE. 4121 02:31:48,440 --> 02:31:51,360 AND I WANT TO ASK TO ALL THE 4122 02:31:51,360 --> 02:31:54,280 PANELISTS AND MAYBE WHEN ALL OUR 4123 02:31:54,280 --> 02:31:59,640 WORKSHOP SPEAKERS THAT ABOUT MY 4124 02:31:59,640 --> 02:32:03,680 QUESTION ABOUT THE PREVALENCE OF 4125 02:32:03,680 --> 02:32:09,680 LYMPHEDEMA BECAUSE CURRENT DATA 4126 02:32:09,680 --> 02:32:12,600 CONTRIBUTED BY MANY -- MANY IN 4127 02:32:12,600 --> 02:32:14,360 THIS WORKSHOP, IT IS AN 4128 02:32:14,360 --> 02:32:16,200 ESTIMATION OF THE PREVALENCE AND 4129 02:32:16,200 --> 02:32:17,840 INCIDENCE, AND IT IS VERY 4130 02:32:17,840 --> 02:32:19,640 COMPLICATED, AND MY QUESTION OR 4131 02:32:19,640 --> 02:32:21,640 MAYBE YOU CAN SAY IT'S A CALL 4132 02:32:21,640 --> 02:32:24,680 FOR ACTION IS THAT HOW CAN WE 4133 02:32:24,680 --> 02:32:29,000 DETERMINE IN THE EPIDEMIOLOGY OF 4134 02:32:29,000 --> 02:32:29,800 LYMPHEDEMA, I THINK IT WOULD 4135 02:32:29,800 --> 02:32:31,760 HELP TO MOVE THE FIELD FORWARD 4136 02:32:31,760 --> 02:32:33,160 AND IF YOU CAN HAVE AN ACTUAL 4137 02:32:33,160 --> 02:32:34,800 INCIDENCE RATE, IT WOULD MAKE A 4138 02:32:34,800 --> 02:32:37,200 GREAT IMPACT. 4139 02:32:37,200 --> 02:32:40,720 LOOKS LIKE STAN IS READY TO JUMP 4140 02:32:40,720 --> 02:32:40,880 IN. 4141 02:32:40,880 --> 02:32:42,200 >> I'LL START. 4142 02:32:42,200 --> 02:32:46,320 SO IT'S QUITE CLEAR THAT WE NEED 4143 02:32:46,320 --> 02:32:47,720 RELEVANT EPIDEMIOLOGY, WHICH HAS 4144 02:32:47,720 --> 02:32:49,400 NEVER BEEN PERFORMED AND WHICH 4145 02:32:49,400 --> 02:32:52,760 NEEDS FUNDING AND NEEDS AN 4146 02:32:52,760 --> 02:32:54,400 INFRASTRUCTURE TO ACCOMPLISH. 4147 02:32:54,400 --> 02:32:57,680 A COUPLE OF INSIGHTS I CAN 4148 02:32:57,680 --> 02:32:58,000 PROVIDE. 4149 02:32:58,000 --> 02:32:59,680 ONE OF THE ESTIMATES THAT WE'VE 4150 02:32:59,680 --> 02:33:02,440 TRIED TO PUT FORWARD IS TO LOOK 4151 02:33:02,440 --> 02:33:06,720 AT THE RELEVANT PREDISPOSING 4152 02:33:06,720 --> 02:33:08,280 FACTORS FOR LYMPHEDEMA, LOOK AT 4153 02:33:08,280 --> 02:33:09,400 THE INCIDENCE OF THOSE FACTORS 4154 02:33:09,400 --> 02:33:11,320 IN THE GENERAL POPULATION. 4155 02:33:11,320 --> 02:33:12,880 THERE ARE MANY STUDIES TO SAY 4156 02:33:12,880 --> 02:33:15,680 THE PERCENTAGE OF PATIENTS WITH 4157 02:33:15,680 --> 02:33:16,880 OVARIAN CANCER THAT DEVELOP 4158 02:33:16,880 --> 02:33:20,120 LYMPHEDEMA IS X, OR SKIN CANCERS 4159 02:33:20,120 --> 02:33:21,600 OR LYMPHOMAS OR WHATEVER THE 4160 02:33:21,600 --> 02:33:22,600 CASE MAY BE, AND WHEN YOU 4161 02:33:22,600 --> 02:33:25,000 AGGRAVATE ALL OF THOSE NUMBERS 4162 02:33:25,000 --> 02:33:27,760 AS WELL AS PREVALENCE RATES IN 4163 02:33:27,760 --> 02:33:28,440 OBESITY AND FOLLOWING INFECTION 4164 02:33:28,440 --> 02:33:30,960 AND SO ON, WE DO COME UP WITH A 4165 02:33:30,960 --> 02:33:34,960 NUMBER THAT LACKS LIKE LOS 4166 02:33:34,960 --> 02:33:36,280 SOMEWHERE BETWEEN 5 AND 4167 02:33:36,280 --> 02:33:36,840 10 MILLION PATIENTS IN THE 4168 02:33:36,840 --> 02:33:37,200 UNITED STATES. 4169 02:33:37,200 --> 02:33:40,200 THE OTHER SET OF PUBLICATIONS 4170 02:33:40,200 --> 02:33:41,360 THAT I'D LIKE TO POINT OUT TO 4171 02:33:41,360 --> 02:33:44,960 THE GENERAL AUDIENCE IS THAT THE 4172 02:33:44,960 --> 02:33:45,840 INTERNATIONAL LYMPHEDEMA 4173 02:33:45,840 --> 02:33:48,640 FRAMEWORK HAS BEEN VERY 4174 02:33:48,640 --> 02:33:50,480 INTERESTED IN PREVALENCE RATES 4175 02:33:50,480 --> 02:33:53,480 OF LYMPHEDEMA AND CHRONIC EDEMA 4176 02:33:53,480 --> 02:33:57,760 WORLDWIDE, AND THERE ARE 4177 02:33:57,760 --> 02:33:59,000 RELEVANT SUBGROUPS IN A VARIETY 4178 02:33:59,000 --> 02:34:00,200 OF COUNTRIES THROUGHOUT THE 4179 02:34:00,200 --> 02:34:00,760 WORLD. 4180 02:34:00,760 --> 02:34:01,600 IN THE JOURNAL LYMPHATIC 4181 02:34:01,600 --> 02:34:03,480 RESEARCH AND BIOLOGY, WE 4182 02:34:03,480 --> 02:34:06,160 PUBLISHED A COMPENDIUM OF THE 4183 02:34:06,160 --> 02:34:08,240 STUDIES THAT WERE SPONSORED BY 4184 02:34:08,240 --> 02:34:10,480 ILF, AND THE NUMBERS ARE 4185 02:34:10,480 --> 02:34:11,000 SURPRISINGLY HIGH. 4186 02:34:11,000 --> 02:34:14,520 FOR EXAMPLE, ONE STUDY WHICH I 4187 02:34:14,520 --> 02:34:16,480 BELIEVE WAS DONE IN THE U.K. 4188 02:34:16,480 --> 02:34:18,200 LOOKED AT PREVALENCE RATES OF 4189 02:34:18,200 --> 02:34:19,640 CHRONIC EDEMA AMONG HOSPITALIZED 4190 02:34:19,640 --> 02:34:21,000 PATIENTS AND IT WAS AS LIE HIGH 4191 02:34:21,000 --> 02:34:23,840 AS HIGH AS 4192 02:34:23,840 --> 02:34:24,080 OVER 30%. 4193 02:34:24,080 --> 02:34:26,040 SO WE KNOW THE NUMBERS ARE HIVE, 4194 02:34:26,040 --> 02:34:29,200 BUT IN ORDER TO SUPPORT THE 4195 02:34:29,200 --> 02:34:31,120 RESEARCH THAT NEEDS TO BE DONE 4196 02:34:31,120 --> 02:34:33,560 TO DEAL WITH THESE PATIENTS, WE 4197 02:34:33,560 --> 02:34:36,960 REALLY DO NEED VERY RIGID 4198 02:34:36,960 --> 02:34:38,160 EPIDEMIOLOGIC STUDIES TO BE ABLE 4199 02:34:38,160 --> 02:34:43,400 TO SUPPORT WHAT WE KNOW. 4200 02:34:43,400 --> 02:34:43,800 >> GREAT. 4201 02:34:43,800 --> 02:34:45,000 THANK YOU. 4202 02:34:45,000 --> 02:34:46,200 DOES ANYONE ELSE WANT TO HOP IN 4203 02:34:46,200 --> 02:34:49,800 ON SELL IN'S SELEN'S QUEST? 4204 02:34:49,800 --> 02:34:53,920 >> I WANT AN ACTION ITEM, LIKE 4205 02:34:53,920 --> 02:34:55,280 ALL OF YOU HAVE SAY, YES, LET'S 4206 02:34:55,280 --> 02:34:56,840 GO DO THIS, WE CAN ACTUALLY 4207 02:34:56,840 --> 02:34:57,920 DETERMINE, SO THAT THE NEXT 4208 02:34:57,920 --> 02:35:00,000 GENERATION OF RESEARCHERS START 4209 02:35:00,000 --> 02:35:01,720 WRITING THEIR GRANTS SAYING THAT 4210 02:35:01,720 --> 02:35:03,320 THE INCIDENCE RATE OF LYMPHEDEMA 4211 02:35:03,320 --> 02:35:05,960 IS SUCH AND SUCH, AND IT IS SO 4212 02:35:05,960 --> 02:35:06,960 MUCH GREATER THAN YOU GUYS 4213 02:35:06,960 --> 02:35:10,520 THINK. 4214 02:35:10,520 --> 02:35:16,640 SO MAYBE IT WOULD HELP. 4215 02:35:16,640 --> 02:35:16,880 ANYWAYS. 4216 02:35:16,880 --> 02:35:18,280 >> WE JUST KNOW THE EXACT 4217 02:35:18,280 --> 02:35:22,360 NUMBER. 4218 02:35:22,360 --> 02:35:25,040 >> DHRUV, IF YOU WANTED TO SAY 4219 02:35:25,040 --> 02:35:25,280 SOMETHING? 4220 02:35:25,280 --> 02:35:26,560 >> YOU AND I HAVE TALKED ABOUT 4221 02:35:26,560 --> 02:35:29,120 THIS AND I COMPLETELY AGREE WITH 4222 02:35:29,120 --> 02:35:30,440 YOUR APPROACH DR. ROCKSON IS 4223 02:35:30,440 --> 02:35:30,760 MENTIONING. 4224 02:35:30,760 --> 02:35:32,080 I THINK ONE OF THE CHALLENGES, 4225 02:35:32,080 --> 02:35:34,200 THOUGH, IS IF YOU CAN'T DEFINE 4226 02:35:34,200 --> 02:35:35,520 IT, IT'S VERY HARD TO GIVE THE 4227 02:35:35,520 --> 02:35:36,640 INCIDENCE OF IT, AND THERE'S A 4228 02:35:36,640 --> 02:35:39,760 LOT OF DIFFERENT DEFINITIONS OUT 4229 02:35:39,760 --> 02:35:42,040 THERE FOR LYMPHEDEMA, AND UNTIL 4230 02:35:42,040 --> 02:35:43,040 THAT'S STANDARDIZED, YOU'RE 4231 02:35:43,040 --> 02:35:44,680 GOING TO HAVE TROUBLE GETTING A 4232 02:35:44,680 --> 02:35:45,640 GOOD NUMBER. 4233 02:35:45,640 --> 02:35:47,040 >> YEAH, I AGREE WITH THAT. 4234 02:35:47,040 --> 02:35:48,880 YOU KNOW, THE 10% NUMBER THAT 4235 02:35:48,880 --> 02:35:51,600 PEOPLE TALK ABOUT, YOU KNOW, 10% 4236 02:35:51,600 --> 02:35:52,880 INCREASE IN LIMB VOLUME, IS 4237 02:35:52,880 --> 02:35:54,080 ACTUALLY A BIG NUMBER. 4238 02:35:54,080 --> 02:35:55,720 THAT'S MORE THAN THREE STANDARD 4239 02:35:55,720 --> 02:35:57,240 DEVIATIONS AWAY FROM WHAT NORMAL 4240 02:35:57,240 --> 02:35:59,200 VARIATIONS IN ARM VOLUME IS. 4241 02:35:59,200 --> 02:36:01,000 SO I THINK THAT'S EXCLUDING A 4242 02:36:01,000 --> 02:36:02,560 LOT OF PEOPLE WHO ACTUALLY HAVE 4243 02:36:02,560 --> 02:36:03,080 LYMPHEDEMA. 4244 02:36:03,080 --> 02:36:04,080 SO I THINK THE DEFINITION IS 4245 02:36:04,080 --> 02:36:04,720 VERY IMPORTANT. 4246 02:36:04,720 --> 02:36:06,920 AND I THINK, YOU KNOW, A VERY 4247 02:36:06,920 --> 02:36:08,200 BIG GAP THAT EVERYONE'S TALKED 4248 02:36:08,200 --> 02:36:10,480 ABOUT IS BEING ABLE TO MEASURE 4249 02:36:10,480 --> 02:36:12,600 LYMPHATIC FUNCTION AK RALTLY, 4250 02:36:12,600 --> 02:36:15,160 AND THEN WE CAN SORT OF SET A 4251 02:36:15,160 --> 02:36:15,920 THRESHOLD THAT'S REALISTIC AS 4252 02:36:15,920 --> 02:36:17,280 OPPOSED TO SOME ARTIFICIAL 4253 02:36:17,280 --> 02:36:18,360 NUMBER THAT PEOPLE HAVE SELECTED 4254 02:36:18,360 --> 02:36:20,040 OUT OF THE AIR. 4255 02:36:20,040 --> 02:36:21,880 >> THANKS. 4256 02:36:21,880 --> 02:36:23,400 SO I'M GOING TO ASK -- FIRST OF 4257 02:36:23,400 --> 02:36:25,000 ALL I WANT TO THANK STAN AGAIN 4258 02:36:25,000 --> 02:36:26,440 FOR HIS WONDERFUL TALK THIS 4259 02:36:26,440 --> 02:36:29,680 MORNING AND FOR GIVING IT AT 4260 02:36:29,680 --> 02:36:30,760 5:30 LOCAL TIME A.M., SO THANKS 4261 02:36:30,760 --> 02:36:31,280 FOR THAT, STAN. 4262 02:36:31,280 --> 02:36:36,760 THERE'S A QUESTION FROMTIVE 4263 02:36:36,760 --> 02:36:38,680 WINEKOPF ABOUT WHETHER YOU'VE 4264 02:36:38,680 --> 02:36:40,560 TREATED ANY PATIENTS THAT 4265 02:36:40,560 --> 02:36:44,160 DEVELOPED LYMPHEDEMA BECAUSE OF 4266 02:36:44,160 --> 02:36:45,480 FILARIAL INFECTIONS WITH ANY OF 4267 02:36:45,480 --> 02:36:46,560 YOUR CLINICAL TRIALS, AND WOULD 4268 02:36:46,560 --> 02:36:50,560 YOU EXPECT SIMILAR INFLAMMATORY 4269 02:36:50,560 --> 02:36:52,320 PATHWAYS TO BE INVOLVED IN THOSE 4270 02:36:52,320 --> 02:36:53,560 PATIENTS? 4271 02:36:53,560 --> 02:36:55,360 >> WELL, I CAN ANSWER THE 4272 02:36:55,360 --> 02:36:57,120 QUESTION INDIRECTLY, WHICH IS TO 4273 02:36:57,120 --> 02:36:59,480 SAY THAT OF COURSE WE SEE VERY 4274 02:36:59,480 --> 02:37:02,680 LITTLE FILARIASIS HERE IN THE 4275 02:37:02,680 --> 02:37:03,640 UNITED STATES AND TYPICALLY THEY 4276 02:37:03,640 --> 02:37:04,680 ARE IMMIGRANTS FROM THE 4277 02:37:04,680 --> 02:37:06,280 COUNTRIES WHERE THE INFECTIONS 4278 02:37:06,280 --> 02:37:06,880 ARE INDEMIC. 4279 02:37:06,880 --> 02:37:08,960 I HAVE TREATED SOME OF THOSE 4280 02:37:08,960 --> 02:37:10,360 PATIENTS, NOT WITHIN OUR 4281 02:37:10,360 --> 02:37:11,800 CLINICAL TRIALS BUT WHAT I CAN 4282 02:37:11,800 --> 02:37:15,480 SAY BY EXTENSION IS THAT IN THE 4283 02:37:15,480 --> 02:37:17,880 KETOPROFEN WORK THAT WENT ON FOR 4284 02:37:17,880 --> 02:37:19,320 ABOUT 10 YEARS, WE DID HAVE THE 4285 02:37:19,320 --> 02:37:21,200 OPPORTUNITY TO TREAT BOTH AN 4286 02:37:21,200 --> 02:37:22,560 OPEN LABEL AND ACTUALLY EVEN IN 4287 02:37:22,560 --> 02:37:25,480 THE PLACEBO CONTROLLED 4288 02:37:25,480 --> 02:37:26,040 COMPONENT. 4289 02:37:26,040 --> 02:37:27,960 PATIENTS WITH STAGE III 4290 02:37:27,960 --> 02:37:29,280 LYMPHEDEMA THAT STRONGLY 4291 02:37:29,280 --> 02:37:30,680 RESEMBLE THE KIND OF DISEASE AND 4292 02:37:30,680 --> 02:37:33,000 THE SEVERITY OF DISEASE THAT WE 4293 02:37:33,000 --> 02:37:36,360 TYPICALLY SEE IN FILARIASIS, AND 4294 02:37:36,360 --> 02:37:38,320 WE DO SEE RESPONSIVENESS. 4295 02:37:38,320 --> 02:37:42,080 SO IT APPEARS THAT THERE IS NOT 4296 02:37:42,080 --> 02:37:44,640 A LATE STAGE BEYOND WHICH ONE 4297 02:37:44,640 --> 02:37:46,480 CANNOT MEANINGFULLY INTERVENE, 4298 02:37:46,480 --> 02:37:50,080 WHICH WOULD LEAD ME TO BELIEVE 4299 02:37:50,080 --> 02:37:55,480 THAT FILARIASIS AND FILARIATIT 4300 02:37:55,480 --> 02:37:56,480 LYMPHEDEMA CAN BE A TARGET IN 4301 02:37:56,480 --> 02:37:58,280 THE FUTURE FOR PHARMACOTHERAPY, 4302 02:37:58,280 --> 02:37:59,640 BUT WE HAVE A WAYS TO GO BEFORE 4303 02:37:59,640 --> 02:38:04,320 WE'RE GOING TO GET TO THAT 4304 02:38:04,320 --> 02:38:04,560 POINT. 4305 02:38:04,560 --> 02:38:05,000 >> THANKS. 4306 02:38:05,000 --> 02:38:06,160 THIS QUESTION WAS DIRECT TODAY 4307 02:38:06,160 --> 02:38:07,480 DHRUV BUT I THINK ALSO IS 4308 02:38:07,480 --> 02:38:10,440 RELEVANT, SO WE'LL LET DHRUV 4309 02:38:10,440 --> 02:38:11,640 ANSWER BUT YOU MIGHT HAVE SOME 4310 02:38:11,640 --> 02:38:12,880 COMMENT AS WELL, WHICH IS, 4311 02:38:12,880 --> 02:38:14,000 DHRUV, DO YOU THINK THE AMOUNT 4312 02:38:14,000 --> 02:38:16,400 OF CELLULAR INJURY AND 4313 02:38:16,400 --> 02:38:20,480 INFLAMMATION AT THE TIME OF 4314 02:38:20,480 --> 02:38:22,080 TRANS SECTION CONTRIBUTES TO THE 4315 02:38:22,080 --> 02:38:22,720 RISK OF LYMPHEDEMA? 4316 02:38:22,720 --> 02:38:23,720 >> THANKS, TIM. 4317 02:38:23,720 --> 02:38:25,760 I THINK WHEN I THINK ABOUT 4318 02:38:25,760 --> 02:38:27,520 CELLULAR INJURY OR INJURY 4319 02:38:27,520 --> 02:38:28,840 OCCURRING FROM SURGERY, I'M NOT 4320 02:38:28,840 --> 02:38:30,360 REALLY SURE THAT THAT'S AS 4321 02:38:30,360 --> 02:38:34,400 IMPORTANT AS THE OVERALL 4322 02:38:34,400 --> 02:38:35,680 INFLAMMATORY RESPONSE. 4323 02:38:35,680 --> 02:38:38,080 IT'S HARD NOT TO IMAGINE THAT 4324 02:38:38,080 --> 02:38:39,200 INFLAMMATION DOESN'T PLAY A 4325 02:38:39,200 --> 02:38:42,120 SIGNIFICANT ROLE IN THE BODY'S 4326 02:38:42,120 --> 02:38:43,640 ABILITY TO GENERATE LYMPHATICS. 4327 02:38:43,640 --> 02:38:46,280 IF YOULY SON TO DR. ROCK SOP'S 4328 02:38:46,280 --> 02:38:49,840 LECTURE, DR. NICOLLS' LECTURE, 4329 02:38:49,840 --> 02:38:51,280 YOUR LECTURE, INFLAMMATION IS 4330 02:38:51,280 --> 02:38:52,280 SUCH A KEY DRIVER. 4331 02:38:52,280 --> 02:38:56,240 AND IF YOU LOOK AT BMI, ELEVATED 4332 02:38:56,240 --> 02:38:59,840 BMI LEEFDZ TO LEADS TO A HF 4333 02:38:59,840 --> 02:39:01,680 LYMPHEDEMA, SO I THINK IT'S 4334 02:39:01,680 --> 02:39:04,560 ABOUT THE INDIVIDUAL'S BASELINE 4335 02:39:04,560 --> 02:39:05,080 INFLAMMATORY RESPONSE THAT 4336 02:39:05,080 --> 02:39:06,160 LIKELY PLAYS THE MOST CRITICAL 4337 02:39:06,160 --> 02:39:09,120 ROLE. 4338 02:39:09,120 --> 02:39:12,200 >> SO ONE ADDITIONAL THOUGHT IS 4339 02:39:12,200 --> 02:39:14,080 THAT -- AND I AGREE WITH ALL OF 4340 02:39:14,080 --> 02:39:16,920 THAT, THAT A COMMON PATTERN THAT 4341 02:39:16,920 --> 02:39:19,320 WE SEE AMONG THESE ACQUIRED 4342 02:39:19,320 --> 02:39:20,280 LYMPHEDEMA PATIENTS IS THAT 4343 02:39:20,280 --> 02:39:22,840 THERE IS THIS PERIOD OF LATENCY 4344 02:39:22,840 --> 02:39:24,880 AND OFTEN THERE IS EITHER A 4345 02:39:24,880 --> 02:39:28,040 DEFINED OR SOMETIMES AN 4346 02:39:28,040 --> 02:39:30,520 UNDEFINED ADDITIONAL INJURY OR 4347 02:39:30,520 --> 02:39:33,520 STIMULUS THAT THEN DRIVES THE 4348 02:39:33,520 --> 02:39:34,840 OVERDEVELOPMENT OF LYMPHEDEMA. 4349 02:39:34,840 --> 02:39:37,520 THE PATIENT MAY HAVE AN INSECT 4350 02:39:37,520 --> 02:39:39,920 BIDE BYTE OR THEY MIGHT HAVE A 4351 02:39:39,920 --> 02:39:41,200 MINOR TRAUMA TO THE SKIN, LET'S 4352 02:39:41,200 --> 02:39:43,400 SAY 9 OR 12 MONTHS OUT FROM 4353 02:39:43,400 --> 02:39:45,480 RADIOTHERAPY, AND THEN DEVELOP 4354 02:39:45,480 --> 02:39:45,880 OVERT LYMPHEDEMA. 4355 02:39:45,880 --> 02:39:47,640 SO I THINK WHAT WE CAN SAY BY 4356 02:39:47,640 --> 02:39:51,160 EXTENSION IS THAT THERE IS A 4357 02:39:51,160 --> 02:39:53,120 CAPACITY FOR LATENCY WHEN THERE 4358 02:39:53,120 --> 02:39:56,520 HAS BEEN A LYMPHATIC SURGICAL OR 4359 02:39:56,520 --> 02:39:57,640 RADIO THERAPEUTIC INJURY, BUT 4360 02:39:57,640 --> 02:39:59,000 THAT THE DEGREE OF DAMAGE IS 4361 02:39:59,000 --> 02:40:02,720 GOING TO DETERMINE THE EXTENT TO 4362 02:40:02,720 --> 02:40:04,360 WHICH THAT LATENCY CAN BE 4363 02:40:04,360 --> 02:40:06,600 MAINTAINED, AND CONVERSELY, THE 4364 02:40:06,600 --> 02:40:10,560 MORE MINOR THE TRAUMA, IT MAY BE 4365 02:40:10,560 --> 02:40:11,760 DEFINE THE DEGREE OF INJURY 4366 02:40:11,760 --> 02:40:13,040 THAT'S REQUIRED TO TRANSFORM 4367 02:40:13,040 --> 02:40:16,320 FROM A LATENT LYMPHATIC DAMAGE 4368 02:40:16,320 --> 02:40:19,160 TO ONE THAT IS OVERTLY 4369 02:40:19,160 --> 02:40:19,440 LYMPHEDEMA. 4370 02:40:19,440 --> 02:40:22,000 ONCE THE LYMPHEDEMA DEVELOPS, IT 4371 02:40:22,000 --> 02:40:23,720 TENDS TO BE SELF-SUSTAINING AND 4372 02:40:23,720 --> 02:40:27,000 ACTUALLY SELF-EXPONENTIALLY 4373 02:40:27,000 --> 02:40:27,320 EXPANDING. 4374 02:40:27,320 --> 02:40:29,280 SO IT'S REALLY THAT TRANSITION 4375 02:40:29,280 --> 02:40:32,080 FROM LATENCY TO ACTIVE 4376 02:40:32,080 --> 02:40:32,880 INFLAMMATORY RESPONSE IN THE 4377 02:40:32,880 --> 02:40:34,320 TISSUES. 4378 02:40:34,320 --> 02:40:36,800 >> THANKS. 4379 02:40:36,800 --> 02:40:41,360 I'M GOING TO HAND THE MIC OVER 4380 02:40:41,360 --> 02:40:44,360 TO BABAK TO ASK A QUESTION OF 4381 02:40:44,360 --> 02:40:47,000 MARK SHA 4382 02:40:47,000 --> 02:40:47,880 MARC SCHAVERIEN. 4383 02:40:47,880 --> 02:40:49,160 YOU WERE ASKING ABOUT HOW 4384 02:40:49,160 --> 02:40:50,040 PATIENT OUTCOMES AFTER -- 4385 02:40:50,040 --> 02:40:51,000 >> O I REMEMBER NOW. 4386 02:40:51,000 --> 02:40:51,800 YES. 4387 02:40:51,800 --> 02:40:54,120 >> SORRY TO PUT YOU ON THE SPOT. 4388 02:40:54,120 --> 02:40:55,560 >> MY LYMPHATICS TO MY BRAIN 4389 02:40:55,560 --> 02:40:58,360 AREN'T WORKING VERY WELL. 4390 02:40:58,360 --> 02:40:59,000 MARC, I HAD A QUESTION. 4391 02:40:59,000 --> 02:41:01,360 DO YOU FIND THAT ANY OF YOUR 4392 02:41:01,360 --> 02:41:02,480 PATIENTS GET WORSE AFTER 4393 02:41:02,480 --> 02:41:02,880 SURGERY? 4394 02:41:02,880 --> 02:41:04,280 WE FIND THAT SOME OF OUR 4395 02:41:04,280 --> 02:41:05,280 PATIENTS GET BETTER BUT THERE 4396 02:41:05,280 --> 02:41:06,920 ARE SOME WHO DON'T GET BETTER 4397 02:41:06,920 --> 02:41:08,520 AND SOME WHO ACTUALLY GET A 4398 02:41:08,520 --> 02:41:11,920 LITTLE BIT WORSE. 4399 02:41:11,920 --> 02:41:13,760 AND IF SO, HAVE YOU IDENTIFIED 4400 02:41:13,760 --> 02:41:14,880 PATIENT POPULATIONS THAT MAY 4401 02:41:14,880 --> 02:41:17,360 MOST BENEFIT FROM LYMPH NODE 4402 02:41:17,360 --> 02:41:17,640 TRANSPLANT? 4403 02:41:17,640 --> 02:41:21,200 >> THANKS, BABAK. 4404 02:41:21,200 --> 02:41:22,480 SO I DON'T THINK WE HAVE 4405 02:41:22,480 --> 02:41:24,600 PATIENTS THAT HAVE GOT WORSE. 4406 02:41:24,600 --> 02:41:26,640 THAT PROBABLY COMES DOWN TO THE 4407 02:41:26,640 --> 02:41:27,480 PATIENT SELECTION. 4408 02:41:27,480 --> 02:41:30,000 SO IT'S REALLY IMPORTANT THAT 4409 02:41:30,000 --> 02:41:32,080 PATIENTS ARE COMPLIANT, AND IF 4410 02:41:32,080 --> 02:41:33,160 WE HAVE THEM STABLE AND 4411 02:41:33,160 --> 02:41:34,560 PLATEAUING BEFORE THEY GO TO 4412 02:41:34,560 --> 02:41:36,320 SURGERY, AND THEN THEY CONTINUE 4413 02:41:36,320 --> 02:41:37,680 THAT AFTER SURGERY UNTIL WE 4414 02:41:37,680 --> 02:41:39,360 START SEEING AN IMPROVEMENT, 4415 02:41:39,360 --> 02:41:40,480 THEN WE WOULDN'T EXPECT THEM TO 4416 02:41:40,480 --> 02:41:40,880 GET WORSE. 4417 02:41:40,880 --> 02:41:42,200 NOW THERE IS A POPULATION THAT 4418 02:41:42,200 --> 02:41:43,960 DOESN'T SEEM TO BENEFIT, AND 4419 02:41:43,960 --> 02:41:45,440 THAT'S WHAT I WAS ALLUDING TO IN 4420 02:41:45,440 --> 02:41:50,080 THE KNOWLEDGE GAPS, AND REALLY 4421 02:41:50,080 --> 02:41:54,200 THOUGHT PROVOKING SOME OF THESE 4422 02:41:54,200 --> 02:41:55,080 TALKS, THESE PATIENTS HAVING A 4423 02:41:55,080 --> 02:41:58,240 HIGH INFLAMMATORY STATE, THESE 4424 02:41:58,240 --> 02:42:00,040 PATIENTS ARE VERY HARD TO 4425 02:42:00,040 --> 02:42:01,080 CONTROL WITH CONSERVATIVE 4426 02:42:01,080 --> 02:42:03,160 THERAPY AND WITH SURGERY, AND I 4427 02:42:03,160 --> 02:42:04,680 DO CERTAINLY IDENTIFY THERE 4428 02:42:04,680 --> 02:42:07,840 SEEMS TO BE A RELATIONSHIP 4429 02:42:07,840 --> 02:42:10,560 WITH -- CHEMOTHERAPY, AND 4430 02:42:10,560 --> 02:42:12,640 PREVIOUS INFECTIONS. 4431 02:42:12,640 --> 02:42:14,920 SO REALLY I'M UNSURE AS TO 4432 02:42:14,920 --> 02:42:16,120 WHETHER THEY AT BASELINE HAVE A 4433 02:42:16,120 --> 02:42:17,320 HIGHER INFLAMMATORY RESPONSE OR 4434 02:42:17,320 --> 02:42:19,160 WHETHER IT IS SIMPLY KIND OF 4435 02:42:19,160 --> 02:42:21,560 ACCUMULATED INJURY FROM THE 4436 02:42:21,560 --> 02:42:23,080 TREATMENTS AND THEN EPISODES OF 4437 02:42:23,080 --> 02:42:24,360 INFECTION THAT MAYBE LEAD INTO 4438 02:42:24,360 --> 02:42:26,320 THIS HIGHLY INFLAMMATORY STATE. 4439 02:42:26,320 --> 02:42:27,400 I THINK THESE PATIENTS WILL BE 4440 02:42:27,400 --> 02:42:31,960 BEST MANAGED IN THE FUTURE BY -- 4441 02:42:31,960 --> 02:42:33,720 CO-MANAGED WITH SURGERY AND WITH 4442 02:42:33,720 --> 02:42:36,160 ANTI-INFLAMMATORY MEDICATIONS 4443 02:42:36,160 --> 02:42:38,440 AND WE'RE REALLY EXCITED TO SEE 4444 02:42:38,440 --> 02:42:42,680 NEW THINGS POTENTIALLY BEING 4445 02:42:42,680 --> 02:42:43,880 CHARTED THAT MIGHT BE IN THE 4446 02:42:43,880 --> 02:42:44,160 PIPELINE. 4447 02:42:44,160 --> 02:42:49,680 >> THANK YOU. 4448 02:42:49,680 --> 02:42:50,320 SHELLEY, THERE'S A QUESTION 4449 02:42:50,320 --> 02:42:52,720 ABOUT WHETHER YOU COMPARED YOUR 4450 02:42:52,720 --> 02:42:56,760 IMAGING OF LIPEDEMA TO OBESE 4451 02:42:56,760 --> 02:43:00,480 PATIENTS, ESPECIALLY THOSE THAT 4452 02:43:00,480 --> 02:43:01,840 HAVE AS A FAMILY CARRY MORE 4453 02:43:01,840 --> 02:43:03,760 WEIGHT IN THEIR HIP AND LOWER 4454 02:43:03,760 --> 02:43:05,000 EXTREMITY REGIONS, AND IF SO, 4455 02:43:05,000 --> 02:43:06,160 WERE THERE ANY DIFFERENCES? 4456 02:43:06,160 --> 02:43:06,480 >> SURE. 4457 02:43:06,480 --> 02:43:09,280 THANKS FOR THE QUESTION. 4458 02:43:09,280 --> 02:43:11,240 SO I THINK IT'S A GREAT IDEA TO 4459 02:43:11,240 --> 02:43:12,680 KIND OF -- IF I UNDERSTAND THE 4460 02:43:12,680 --> 02:43:14,320 QUESTION RIGHT, GO AHEAD AND 4461 02:43:14,320 --> 02:43:16,040 SUBPARSE OUT LIKE THE CONTROL 4462 02:43:16,040 --> 02:43:17,560 GROUP WITH OBESITY, DEPENDING ON 4463 02:43:17,560 --> 02:43:18,560 THEIR BODY COMPOSITION. 4464 02:43:18,560 --> 02:43:20,720 I'M JUST SAY THE DATA WE 4465 02:43:20,720 --> 02:43:22,120 PRESENTED IN LIPEDEMA HAS BEEN 4466 02:43:22,120 --> 02:43:24,120 COMPARED TO BMI-MATCHED COHORTS. 4467 02:43:24,120 --> 02:43:25,800 SO SOME OF THOSE ARE OBESE, SOME 4468 02:43:25,800 --> 02:43:26,720 ARE NOT, BUT ALL OF THE DATA 4469 02:43:26,720 --> 02:43:29,160 WE'VE LOOKED AT SO FAR IS 4470 02:43:29,160 --> 02:43:30,640 COMPARING LIPEDEMA TO THOSE WITH 4471 02:43:30,640 --> 02:43:32,360 SIMILAR OBESITY BUT WITHOUT 4472 02:43:32,360 --> 02:43:33,720 LIPEDEMA, AND THEY'RE 4473 02:43:33,720 --> 02:43:35,240 DIFFERENTIATED BASED ON OTHER 4474 02:43:35,240 --> 02:43:36,440 CHARACTERISTICS LIKE WHETHER 4475 02:43:36,440 --> 02:43:39,000 THEY HAVE EASY BRUISING OR PAIN. 4476 02:43:39,000 --> 02:43:40,120 SO -- AND THEN THE QUESTION 4477 02:43:40,120 --> 02:43:41,880 LEADS WHETHER SOMEONE WITH -- 4478 02:43:41,880 --> 02:43:43,920 WHO CARRIES THEIR WEIGHT AS AN 4479 02:43:43,920 --> 02:43:45,240 OBESE PATIENT IN THE LOWER 4480 02:43:45,240 --> 02:43:46,080 EXTREMITIES ALREADY, AND WE 4481 02:43:46,080 --> 02:43:47,840 MIGHT WANT TO QUESTION WHETHER 4482 02:43:47,840 --> 02:43:49,680 THEY HAVE LIPEDEMA AND THAT'S 4483 02:43:49,680 --> 02:43:50,000 ONE THOUGHT. 4484 02:43:50,000 --> 02:43:52,960 BUT THERE ARE OTHER CONDITIONS, 4485 02:43:52,960 --> 02:43:53,640 MAYBE HYPOTHYROIDISM THAT CAN 4486 02:43:53,640 --> 02:43:54,920 CHANGE PEOPLE'S WEIGHT 4487 02:43:54,920 --> 02:43:55,440 DISTRIBUTION. 4488 02:43:55,440 --> 02:43:57,120 SO I THINK IT'S A GREAT IDEA TO 4489 02:43:57,120 --> 02:44:01,040 KIND OF LACK AT THAT LOOP 4490 02:44:01,040 --> 02:44:02,160 SEPARATELY AND I APPRECIATE THE 4491 02:44:02,160 --> 02:44:03,000 SUGGESTION TO DO THAT, BUT AT 4492 02:44:03,000 --> 02:44:04,400 THIS TIME, WE HAVEN'T LOOKED AT 4493 02:44:04,400 --> 02:44:07,000 DIFFERENT CLASSIFICATIONS WITHIN 4494 02:44:07,000 --> 02:44:08,320 THE OBESE COHORT. 4495 02:44:08,320 --> 02:44:09,800 I HOPE THAT ANSWERS THE 4496 02:44:09,800 --> 02:44:10,200 QUESTION. 4497 02:44:10,200 --> 02:44:13,040 EMAIL ME IF NOT, WHO ASKED ME. 4498 02:44:13,040 --> 02:44:19,760 >> AND THEN YOU HAD A QUESTION 4499 02:44:19,760 --> 02:44:22,080 FOR DR. SCHAVERIEN AND MAYBE 4500 02:44:22,080 --> 02:44:22,840 DHRUV AS WELL. 4501 02:44:22,840 --> 02:44:25,760 >> BASICALLY HOW DYNAMIC IS THE 4502 02:44:25,760 --> 02:44:26,720 FIBROSIS, IS THAT THE ONE WE'RE 4503 02:44:26,720 --> 02:44:27,200 TALKING ABOUT? 4504 02:44:27,200 --> 02:44:30,760 >> THAT OR -- THAT PLUS THE 4505 02:44:30,760 --> 02:44:31,800 PERINODAL FAT QUESTION. 4506 02:44:31,800 --> 02:44:34,720 >> FOR THOSE WHO'VE BEEN DOING 4507 02:44:34,720 --> 02:44:41,800 SURGERIES IN PATIENTS WITH LYMPH 4508 02:44:41,800 --> 02:44:43,520 NOID TRANSPLANT, HOW IMPORTANT 4509 02:44:43,520 --> 02:44:45,600 IS THE ADIPOSE TISSUE OR FROM 4510 02:44:45,600 --> 02:44:46,960 THE SITE OF TRANSFER AND WHAT 4511 02:44:46,960 --> 02:44:47,960 MARKERS WOULD YOU WANT TO KNOW 4512 02:44:47,960 --> 02:44:49,200 ABOUT THAT ADIPOSE TISSUE 4513 02:44:49,200 --> 02:44:50,640 FUNCTION THAT MIGHT IMPROVE THE 4514 02:44:50,640 --> 02:44:55,520 THERAPIES THAT YOU'RE PROVIDING? 4515 02:44:55,520 --> 02:44:56,160 >> THANK YOU. 4516 02:44:56,160 --> 02:44:59,320 I CAN ANSWER THE FIRST PART, I 4517 02:44:59,320 --> 02:45:00,440 PROBABLY CAN'T ANSWER THE SECOND 4518 02:45:00,440 --> 02:45:00,880 PART OF THAT. 4519 02:45:00,880 --> 02:45:03,600 IT'S REALLY IMPORTANT TO BRING 4520 02:45:03,600 --> 02:45:08,520 THAT PERINODAL TISSUE. 4521 02:45:08,520 --> 02:45:13,320 TRANSPLANT IS A -- ASIDE FROM 4522 02:45:13,320 --> 02:45:14,240 LYMPH NODES IN THE TISSUE THAT 4523 02:45:14,240 --> 02:45:16,480 YOU WANT TO TRANSPLANT. 4524 02:45:16,480 --> 02:45:17,800 SO -- AND THAT'S PARTICULARLY 4525 02:45:17,800 --> 02:45:19,960 THE CASE FOR INTERABDOMINAL 4526 02:45:19,960 --> 02:45:22,040 TRANSFERS. 4527 02:45:22,040 --> 02:45:24,960 FOR THE -- I THINK IN SOME 4528 02:45:24,960 --> 02:45:29,680 CASES, THESE ARE IMPORTANT TO 4529 02:45:29,680 --> 02:45:31,120 ACTUALLY TRANSFER -- THERE ARE 4530 02:45:31,120 --> 02:45:33,040 INITIAL BENEFITS FROM 4531 02:45:33,040 --> 02:45:34,480 TRANSFERRING THE SKIN -- 4532 02:45:34,480 --> 02:45:35,560 LYMPHATIC VESSELS AS A 4533 02:45:35,560 --> 02:45:36,760 COMPOSITE, AND I HAVE FOUND IF 4534 02:45:36,760 --> 02:45:39,280 YOU SUBSEQUENTLY REMOVE THAT 4535 02:45:39,280 --> 02:45:41,360 SKIN PADDLE, IT CAN HAVE A 4536 02:45:41,360 --> 02:45:42,960 SLIGHT DET RISM TO THE FINAL 4537 02:45:42,960 --> 02:45:44,400 RESULT, SO THERE'S MANY 4538 02:45:44,400 --> 02:45:46,360 INTERESTING THINGS GOING ON 4539 02:45:46,360 --> 02:45:48,120 HERE, EVEN BEYOND JUST THE LYMPH 4540 02:45:48,120 --> 02:45:50,840 NODE COMPONENT ITSELF, BUT 4541 02:45:50,840 --> 02:45:54,640 HAVING SAID THAT, THE LYMPH NODE 4542 02:45:54,640 --> 02:45:56,400 COMPONENT AND ITS PERINODAL 4543 02:45:56,400 --> 02:45:58,360 LYMPHATIC TISSUE, IN MY OPINION, 4544 02:45:58,360 --> 02:46:02,200 IS REALLY THE MAIN POWERHOUSE OF 4545 02:46:02,200 --> 02:46:03,080 THESE TRANSPLANTS. 4546 02:46:03,080 --> 02:46:06,320 IT IS A VERY POWERFUL TREATMENT 4547 02:46:06,320 --> 02:46:08,640 IN WELL SELECTED PATIENTS. 4548 02:46:08,640 --> 02:46:11,040 PRETTY MUCH I'M USING IT FOR 4549 02:46:11,040 --> 02:46:12,240 MOST STAGES OF LYMPHEDEMA NOW, 4550 02:46:12,240 --> 02:46:16,080 APART FROM THOSE PATIENTS VERY 4551 02:46:16,080 --> 02:46:17,440 EARLY WHO WERE PAST CANDIDATES 4552 02:46:17,440 --> 02:46:19,440 AND CAN AVOID A MORE COMPLEX 4553 02:46:19,440 --> 02:46:20,560 POTENTIALLY MORE BIG SURGERY, 4554 02:46:20,560 --> 02:46:23,280 AND THEN THOSE WERE VERY SEVERE, 4555 02:46:23,280 --> 02:46:26,480 LARGE EXTREMITIES THAT ARE A 4556 02:46:26,480 --> 02:46:27,720 FUNCTIONAL ISSUE, THOSE PATIENTS 4557 02:46:27,720 --> 02:46:30,160 ARE BEST TREATED FIRST BY 4558 02:46:30,160 --> 02:46:33,440 DEBULKING SUBSEQUENTLY, LYMPH 4559 02:46:33,440 --> 02:46:37,480 NODE TRANTS TRANSPLANTS ONCE 4560 02:46:37,480 --> 02:46:38,440 BEEN DOWN STAGED. 4561 02:46:38,440 --> 02:46:40,720 I CAN'T ANSWER YOUR OTHER 4562 02:46:40,720 --> 02:46:40,960 QUESTION. 4563 02:46:40,960 --> 02:46:42,040 >> ACTUALLY I'M GOING TO MOVE 4564 02:46:42,040 --> 02:46:42,800 THE CONVERSATION BECAUSE I SORT 4565 02:46:42,800 --> 02:46:47,560 OF HAVE A QUESTION FOR MARK 4566 02:46:47,560 --> 02:46:48,080 NICOLLS. 4567 02:46:48,080 --> 02:46:50,040 IT'S REALLY SORT OF INSPIRED BY 4568 02:46:50,040 --> 02:46:51,880 LISTENING TO ROCHELLE'S TALK, 4569 02:46:51,880 --> 02:46:54,280 WHICH WE'VE HEARD ABOUT ALL THE 4570 02:46:54,280 --> 02:46:56,480 INFORMATION THAT'S BEEN 4571 02:46:56,480 --> 02:47:00,040 HAPPENING WITH LYMPHEDEMA, AND 4572 02:47:00,040 --> 02:47:02,480 CHELLI IS SLOWING THIS ELEVATED 4573 02:47:02,480 --> 02:47:03,000 SALT CONTENT. 4574 02:47:03,000 --> 02:47:04,280 COULD SODIUM IN THE SKIN 4575 02:47:04,280 --> 02:47:05,800 ACTUALLY BE TRIGGERING SOME OF 4576 02:47:05,800 --> 02:47:07,040 THESE PATHWAYS? 4577 02:47:07,040 --> 02:47:09,880 MAYBE CHELLI WANTS TO JUMP IN ON 4578 02:47:09,880 --> 02:47:10,440 THAT AS WELL. 4579 02:47:10,440 --> 02:47:13,440 >> I'M GOING TO LET CHELLI JUMP 4580 02:47:13,440 --> 02:47:13,600 IN. 4581 02:47:13,600 --> 02:47:15,840 >> THANKS FOR RECOGNIZING THAT 4582 02:47:15,840 --> 02:47:18,800 SODIUM IS VIEWED AS INFLAMMATORY 4583 02:47:18,800 --> 02:47:20,320 IN JOINT DISEASES, AND I'M 4584 02:47:20,320 --> 02:47:22,160 THINKING OF THE SODIUM MRI 4585 02:47:22,160 --> 02:47:23,480 LITERATURE. 4586 02:47:23,480 --> 02:47:25,000 I'M LESS FAMILIAR OBVIOUSLY WITH 4587 02:47:25,000 --> 02:47:27,040 THE INTERSTITIAL PHYSIOLOGY BUT 4588 02:47:27,040 --> 02:47:28,280 MY UNDERSTANDING IS THAT SODIUM 4589 02:47:28,280 --> 02:47:31,200 HAS A RECEPTOR ON CERTAIN EITHER 4590 02:47:31,200 --> 02:47:32,720 MACROPHAGES OR IN DIFFERENT 4591 02:47:32,720 --> 02:47:36,680 IMMUNE CELLS, THE -- BP BINDING 4592 02:47:36,680 --> 02:47:40,160 PROTEIN AND IT'S A SENSOR FOR 4593 02:47:40,160 --> 02:47:42,040 SODIUM IN THE INTERSTITIAL 4594 02:47:42,040 --> 02:47:42,280 SPACE. 4595 02:47:42,280 --> 02:47:43,400 SO I HAVE A LOT OF QUESTIONS 4596 02:47:43,400 --> 02:47:44,520 THAT FOLLOW UP FROM THAT 4597 02:47:44,520 --> 02:47:46,280 OBSERVATION IN THAT STUDY, BUT I 4598 02:47:46,280 --> 02:47:47,720 THINK THERE'S POTENTIAL FOR TO 4599 02:47:47,720 --> 02:47:49,520 BE PART OF THE STORY. 4600 02:47:49,520 --> 02:47:52,280 I WOULD BE CAUTIOUS TO SAY THAT 4601 02:47:52,280 --> 02:47:53,360 SODIUM IS DIRECTLY A DRIVER 4602 02:47:53,360 --> 02:47:54,760 BECAUSE I THINK THERE'S A LOT OF 4603 02:47:54,760 --> 02:47:56,800 THINGS GOING ON IN THE LYMPH 4604 02:47:56,800 --> 02:47:59,800 FLUID, THESE NICE INVEE STROH 4605 02:47:59,800 --> 02:48:01,560 STUDIES, RAGHU'S STUDY AS WELL 4606 02:48:01,560 --> 02:48:04,480 SHOWED THAT FROM THESE MARKERS, 4607 02:48:04,480 --> 02:48:05,920 SODIUM IS ONE PART OF THAT BUT 4608 02:48:05,920 --> 02:48:07,240 MAYBE THESE OTHER MARKERS AS 4609 02:48:07,240 --> 02:48:08,760 WELL THAT CAN INDUCE 4610 02:48:08,760 --> 02:48:09,960 INFLAMMATION. 4611 02:48:09,960 --> 02:48:12,040 >> AND SELEN, I THINK YOU HAVE A 4612 02:48:12,040 --> 02:48:14,120 QUESTION FOR RAGHU? 4613 02:48:14,120 --> 02:48:17,280 >> YEAH, RAGHU, I WAS GOING TO 4614 02:48:17,280 --> 02:48:18,800 ASK, IT LOOKS LIKE YOU 4615 02:48:18,800 --> 02:48:21,760 DETERMINED QUITE A BIT OF 4616 02:48:21,760 --> 02:48:22,720 MARKERS, INFLAMMATORY MARKERS 4617 02:48:22,720 --> 02:48:26,200 AND OTHERS IN THESE LYMPHEDEMA 4618 02:48:26,200 --> 02:48:26,680 PATIENTS. 4619 02:48:26,680 --> 02:48:29,080 SO CAN THOSE BE USED FOR 4620 02:48:29,080 --> 02:48:32,000 BASICALLY LOOKING FOR THE 4621 02:48:32,000 --> 02:48:34,520 DIAGNOSTIC PURPOSES OR MARKING 4622 02:48:34,520 --> 02:48:37,400 THE STAGES? 4623 02:48:37,400 --> 02:48:41,040 >> I THINK IT'S MORE OF A 4624 02:48:41,040 --> 02:48:41,840 CLINICIAN'S QUESTION. 4625 02:48:41,840 --> 02:48:43,040 A CLINICIAN CAN ANSWER IT BETTER 4626 02:48:43,040 --> 02:48:43,400 THAN ME. 4627 02:48:43,400 --> 02:48:51,440 AS FAR AS I KNOW -- IB FLAM TRIN 4628 02:48:51,440 --> 02:48:53,520 PATIENT SO MAYBE THAT COULD BE 4629 02:48:53,520 --> 02:48:55,800 USED AS A DIAGNOSTIC MARKER, BUT 4630 02:48:55,800 --> 02:48:58,520 FROM OUR STANDPOINT BASED ON MY 4631 02:48:58,520 --> 02:49:03,320 DATA, BASED ON OUR DATA, THE 4632 02:49:03,320 --> 02:49:05,520 KERATIN UPREGULATIONS SEEMS TO 4633 02:49:05,520 --> 02:49:07,480 BE -- COULD BE POTENTIALLY BE 4634 02:49:07,480 --> 02:49:13,600 USED AS A DIAGNOSTIC MARKER, BUT 4635 02:49:13,600 --> 02:49:17,520 AGAIN -- CAN ACTUALLY ANSWER 4636 02:49:17,520 --> 02:49:19,400 THIS -- LIKE BABAK CAN ANSWER 4637 02:49:19,400 --> 02:49:20,480 THIS QUESTION BETTER THAN ME. 4638 02:49:20,480 --> 02:49:22,240 >> DO YOU WANT TO JUMP IN, 4639 02:49:22,240 --> 02:49:22,440 BABAK? 4640 02:49:22,440 --> 02:49:23,000 >> SURE. 4641 02:49:23,000 --> 02:49:25,160 YOU KNOW, I THINK THE PROBLEM 4642 02:49:25,160 --> 02:49:26,240 WITH SOME OF THE SKIN STUFF IS 4643 02:49:26,240 --> 02:49:27,920 WE NEED TO DO A BIOPSY AND I 4644 02:49:27,920 --> 02:49:30,400 THINK THAT'S INVASIVE. 4645 02:49:30,400 --> 02:49:32,920 I THINK MAYBE WE CAN TEAM UP 4646 02:49:32,920 --> 02:49:34,680 WITH RACHELLE TO LOOK UP FOR 4647 02:49:34,680 --> 02:49:36,760 NONINVASIVE WAYS TO ASSESS SKIN 4648 02:49:36,760 --> 02:49:36,960 CHANGES. 4649 02:49:36,960 --> 02:49:39,240 I THINK THAT MAY BE COOL AND 4650 02:49:39,240 --> 02:49:39,680 INTERESTING. 4651 02:49:39,680 --> 02:49:41,320 I DO THINK IT ONE OF THE FIRST 4652 02:49:41,320 --> 02:49:42,280 MANIFESTATIONS OF LYMPHEDEMA WE 4653 02:49:42,280 --> 02:49:43,920 SEE, THE SKIN, EVEN IN PATIENTS 4654 02:49:43,920 --> 02:49:45,800 WITH MILD DISEASE, IT'S 4655 02:49:45,800 --> 02:49:46,640 DEFINITELY DIFFERENT IF YOU LOOK 4656 02:49:46,640 --> 02:49:49,280 AT IT AND ALSO IF YOU ME SAWYER 4657 02:49:49,280 --> 02:49:50,920 SKIN FLUID CONTENT AND OTHER 4658 02:49:50,920 --> 02:49:56,840 THINGS THAT WE CAN DO SO 4659 02:49:56,840 --> 02:50:01,920 NON-INVAI CIVIL. 4660 02:50:01,920 --> 02:50:02,280 NONINVASIVELY. 4661 02:50:02,280 --> 02:50:06,120 THE METHODS WE USE NOW LIKE 4662 02:50:06,120 --> 02:50:08,800 BIOIMPEDANCE OR CENTIMETER 4663 02:50:08,800 --> 02:50:09,600 CHANGES AND THINGS LIKE THAT. 4664 02:50:09,600 --> 02:50:12,280 SO I HOPE THERE ARE GOOD SORT OF 4665 02:50:12,280 --> 02:50:13,800 NONINVASIVE WAYS TO QUANTIFY 4666 02:50:13,800 --> 02:50:15,640 CHANGES IN THE SKIN, AND I THINK 4667 02:50:15,640 --> 02:50:18,280 THAT COULD BE USED. 4668 02:50:18,280 --> 02:50:20,080 >> I THINK WE HAVE TIME FOR ONE 4669 02:50:20,080 --> 02:50:21,560 LAST QUESTION SO I WANT TO USE 4670 02:50:21,560 --> 02:50:23,200 MY MODERATOR AND ASK DHRUV A 4671 02:50:23,200 --> 02:50:23,760 QUICK QUESTION. 4672 02:50:23,760 --> 02:50:25,240 BECAUSE THIS IS SOMETHING I'VE 4673 02:50:25,240 --> 02:50:26,440 BEEN INTERESTED IN IN HOW AGING 4674 02:50:26,440 --> 02:50:28,080 IS AFFECTING LYMPHATIC FUNCTION 4675 02:50:28,080 --> 02:50:33,040 AND THERE'S A QUESTION FROM 4676 02:50:33,040 --> 02:50:40,440 DEANN NA. 4677 02:50:40,440 --> 02:50:41,960 DOES THE LYMPHATIC ANATOMY IN 4678 02:50:41,960 --> 02:50:44,840 THE ARM CHANGE WITH AGING. 4679 02:50:44,840 --> 02:50:47,440 >> IN THE OR WE IDENTIFY FEWER 4680 02:50:47,440 --> 02:50:49,720 LYMPHATIC CHANNELS BUT IN TERMS 4681 02:50:49,720 --> 02:50:51,040 OF AGING, FROM EITHER ONE, WE 4682 02:50:51,040 --> 02:50:51,960 REALLY DON'T HAVE THE DATA. 4683 02:50:51,960 --> 02:50:53,560 WE'RE JUST TRYING TO FIND 4684 02:50:53,560 --> 02:50:56,720 BASELINE ANATOMY AT THIS POINT, 4685 02:50:56,720 --> 02:50:59,000 AND I HOPE WITH THE R01 AND WHAT 4686 02:50:59,000 --> 02:51:00,120 WE'RE CURRENTLY DOING, WHICH IS 4687 02:51:00,120 --> 02:51:02,640 LOOKING AT A HEALTHY FEMALE 4688 02:51:02,640 --> 02:51:05,320 POPULATION, AGAIN, I HAVE A 4689 02:51:05,320 --> 02:51:06,880 GLIMPSE INTO SOME OF THESE. 4690 02:51:06,880 --> 02:51:08,840 I HEARD, MAYBE I'M WRONG, THAT 4691 02:51:08,840 --> 02:51:10,480 YOU HAVE SOME THOUGHTS ON AGING 4692 02:51:10,480 --> 02:51:10,840 AND LYMPHATICS? 4693 02:51:10,840 --> 02:51:13,200 >> I THINK WE'RE DOING SOME 4694 02:51:13,200 --> 02:51:14,400 EARLY PRELIMINARY WORK ON AGING. 4695 02:51:14,400 --> 02:51:15,920 IT'S INTERESTING, IF YOU LOOK AT 4696 02:51:15,920 --> 02:51:18,560 A LARGE COHORT OF PATIENTS WITH 4697 02:51:18,560 --> 02:51:20,560 LYMPHEDEMA, AGE IS VERY WEAKLEY 4698 02:51:20,560 --> 02:51:22,960 ASSOCIATED WITH LYMPHEDEMA, OR 4699 02:51:22,960 --> 02:51:24,440 AT ALL, OR MAYBE NOT. 4700 02:51:24,440 --> 02:51:26,000 SOMETIMES IN SOME DATABASES THAT 4701 02:51:26,000 --> 02:51:28,840 HAVE BEEN REPORTED, LOWER AGE 4702 02:51:28,840 --> 02:51:30,480 WAS ACTUALLY A HIGHER RISK 4703 02:51:30,480 --> 02:51:31,440 FACTOR FOR LYMPHEDEMA THAN 4704 02:51:31,440 --> 02:51:33,320 HIGHER AGE. 4705 02:51:33,320 --> 02:51:34,960 MAYBE IF YOUNGER PATIENTS CAN 4706 02:51:34,960 --> 02:51:36,600 MOUNT A MORE SIGNIFICANT IMMUNE 4707 02:51:36,600 --> 02:51:36,880 RESPONSE. 4708 02:51:36,880 --> 02:51:38,760 SO I'M NOT SURE THAT THE 4709 02:51:38,760 --> 02:51:39,760 LYMPHATIC ANATOMY CHANGES. 4710 02:51:39,760 --> 02:51:41,520 WE ALL KNOW THAT IT'S NOT 4711 02:51:41,520 --> 02:51:43,800 PARTICULARLY PLASTIC. 4712 02:51:43,800 --> 02:51:45,240 WE DO KNOW LYMPHATICS DON'T WORK 4713 02:51:45,240 --> 02:51:47,440 AS WELL IN ELDERLY MICE AND ALSO 4714 02:51:47,440 --> 02:51:49,360 IN PATIENTS, AND I THINK RAGHU 4715 02:51:49,360 --> 02:51:52,640 AND I ARE WORKING ON SOME -- 4716 02:51:52,640 --> 02:51:54,080 ACTUALLY YOU TOO, TIM, WE'RE 4717 02:51:54,080 --> 02:51:56,920 WORKING ON SOME METHODS TO TRY 4718 02:51:56,920 --> 02:51:59,640 AND QUANTIFY THE INTRACELLULAR 4719 02:51:59,640 --> 02:52:01,400 EFFECTS OF RESPONSES TO VEGF C 4720 02:52:01,400 --> 02:52:02,920 AND HOW THAT CONTRIBUTES TO 4721 02:52:02,920 --> 02:52:05,440 LYMPHATIC FUNCTION. 4722 02:52:05,440 --> 02:52:07,640 >> I THINK IT'S A VERY 4723 02:52:07,640 --> 02:52:08,520 INTERESTING -- FOR THINKING OF 4724 02:52:08,520 --> 02:52:09,840 FUTURE DIRECTIONS OF LYMPHATIC 4725 02:52:09,840 --> 02:52:12,240 RESEARCH OF HOW LYMPHATIC SYSTEM 4726 02:52:12,240 --> 02:52:13,080 DOES EVOLVE WITH AGING. 4727 02:52:13,080 --> 02:52:14,440 SO WE KNOW EVERY OTHER SYSTEM 4728 02:52:14,440 --> 02:52:17,720 EVOLVES WITH AGING, SO IT MAKES 4729 02:52:17,720 --> 02:52:18,520 SENSE LYMPHATICS DO AS WELL. 4730 02:52:18,520 --> 02:52:20,640 WITH THAT, WE NEED TO WRAP UP. 4731 02:52:20,640 --> 02:52:22,280 I APOLOGIZE TO EVERYONE WHOSE 4732 02:52:22,280 --> 02:52:23,520 QUESTIONS I DIDN'T GET TO. 4733 02:52:23,520 --> 02:52:26,520 BUT THE Q & A WILL REMAIN OPEN 4734 02:52:26,520 --> 02:52:27,600 SO IF YOU WERE ONE OF THE 4735 02:52:27,600 --> 02:52:28,840 SPEAKERS AND YOU SEE QUESTIONS 4736 02:52:28,840 --> 02:52:30,720 DIRECTED AT YOU, PLEASE HIT THE 4737 02:52:30,720 --> 02:52:32,360 Q & A AND GET THOSE RESPONDED 4738 02:52:32,360 --> 02:52:34,080 TO, AND I WANT TO THANK ALL THE 4739 02:52:34,080 --> 02:52:35,320 SPEAKERS IN THIS WONDERFUL 4740 02:52:35,320 --> 02:52:37,840 SESSION, AND AGAIN, THANK THE 4741 02:52:37,840 --> 02:52:38,600 ORGANIZERS FOR GIVING ME THE 4742 02:52:38,600 --> 02:52:39,800 PRIVILEGE TO MODERATE IT. 4743 02:52:39,800 --> 02:52:43,960 I THINK WE'RE ON BREAK NOW UNTIL 4744 02:52:43,960 --> 02:52:47,920 11:25, IF I HAVE THAT CORRECT? 4745 02:52:47,920 --> 02:52:49,960 YEP, 11:25, AND SO ENJOY YOUR 4746 02:52:49,960 --> 02:52:51,400 BREAK AND YOU'LL BE BACK 4747 02:52:51,400 --> 02:52:51,640 SHORTLY. 4748 02:52:51,640 --> 02:52:53,520 THANK YOU ALL. 4749 02:52:53,520 --> 02:52:54,560 NEXT I'M DELIGHTED TO INTRODUCE 4750 02:52:54,560 --> 02:52:56,720 THE MEMBERS OF OUR PATIENT 4751 02:52:56,720 --> 02:52:56,920 PANEL. 4752 02:52:56,920 --> 02:52:59,480 I'M JOINED IN THIS SESSION BY 4753 02:52:59,480 --> 02:53:03,600 CYNTHIA HUDSON, CAM AYALA, KASI 4754 02:53:03,600 --> 02:53:04,960 GROSVENOR AND TAYLOR LEWIS. 4755 02:53:04,960 --> 02:53:06,040 THEY'RE GOING TO TELL YOU SOME 4756 02:53:06,040 --> 02:53:07,360 OF THEIR PATIENT EXPERIENCES, AN 4757 02:53:07,360 --> 02:53:09,000 I'M GOING TO LET THEM INTRODUCE 4758 02:53:09,000 --> 02:53:09,680 THEMSELVES. 4759 02:53:09,680 --> 02:53:13,600 MY CO-MODERATOR IS BILL, WILLIAM 4760 02:53:13,600 --> 02:53:17,560 RIPICCI, CEO OF LE&RN. 4761 02:53:17,560 --> 02:53:19,520 PLEASE JOIN ME IN WELCOMING OUR 4762 02:53:19,520 --> 02:53:20,280 PANEL. 4763 02:53:20,280 --> 02:53:20,480 OKAY. 4764 02:53:20,480 --> 02:53:21,040 >> SURE. 4765 02:53:21,040 --> 02:53:22,640 IF THAT'S MY OPPORTUNITY TO 4766 02:53:22,640 --> 02:53:24,040 WELCOME THEM, I WILL SAY, IT WAS 4767 02:53:24,040 --> 02:53:27,160 ONLY A FEW YEARS AGO WHEN IT 4768 02:53:27,160 --> 02:53:31,640 CAME TO NIH, NO PANEL, IT JUST 4769 02:53:31,640 --> 02:53:34,920 WASN'T ALLOWED. 4770 02:53:34,920 --> 02:53:36,720 CATHY BETZ REALLY HELPED US 4771 02:53:36,720 --> 02:53:38,440 BREAK THE MODEL BY COMING TO THE 4772 02:53:38,440 --> 02:53:41,600 FRONT AND NOW YOU ALL ARE -- 4773 02:53:41,600 --> 02:53:42,640 IT'S SO CRITICAL TO HAVE YOUR 4774 02:53:42,640 --> 02:53:43,640 VOICE OUT THERE RATHER THAN 4775 02:53:43,640 --> 02:53:45,000 BEING SPOKEN TO, HAVE THE 4776 02:53:45,000 --> 02:53:46,600 OPPORTUNITY TO SPEAK TO THE 4777 02:53:46,600 --> 02:53:47,160 PEOPLE THAT ARE ACTUALLY 4778 02:53:47,160 --> 02:53:48,040 ATTENDING THIS CONFERENCE TO 4779 02:53:48,040 --> 02:53:49,400 GIVE THEM YOUR PERSPECTIVE, AND 4780 02:53:49,400 --> 02:53:54,480 TO TELL THEM WHAT YOU NEED FROM 4781 02:53:54,480 --> 02:53:57,000 THEM. 4782 02:53:57,000 --> 02:53:59,800 DR. MEHRAR WILL BE HANDLING THE 4783 02:53:59,800 --> 02:54:01,080 FIRST PART AND AT THE END I HOPE 4784 02:54:01,080 --> 02:54:02,680 TO TAKE THE LAST 8 MINUTES FOR 4785 02:54:02,680 --> 02:54:04,480 EACH OF YOU TO HAVE A COUPLE OF 4786 02:54:04,480 --> 02:54:06,240 MINUTES TO TELL THIS AUDIENCE 4787 02:54:06,240 --> 02:54:07,800 WHAT YOU THINK IT IS THEY NEED 4788 02:54:07,800 --> 02:54:09,160 TO KNOW FROM YOU. 4789 02:54:09,160 --> 02:54:11,920 WITH THAT, DR. MEHRARA, I'LL 4790 02:54:11,920 --> 02:54:13,160 TURN IT BACK TO YOU. 4791 02:54:13,160 --> 02:54:13,600 >> THANK YOU, BILL. 4792 02:54:13,600 --> 02:54:14,760 I THINK WE'LL TAKE A FEW MINUTES 4793 02:54:14,760 --> 02:54:17,080 JUST TO GET AI ACQUAINTED WITR 4794 02:54:17,080 --> 02:54:17,360 PANELISTS. 4795 02:54:17,360 --> 02:54:22,200 IF YOU DON'T MIND GIVING JUST A 4796 02:54:22,200 --> 02:54:23,120 SHORT INTRODUCTION ABOUT WHO YOU 4797 02:54:23,120 --> 02:54:25,720 ARE AND HOW LYMPH DISEASE HAS 4798 02:54:25,720 --> 02:54:27,800 IMPACTED YOU, IT WOULD BE GREAT. 4799 02:54:27,800 --> 02:54:31,680 WE'LL START WITH CYNTHIA HUDSON. 4800 02:54:31,680 --> 02:54:37,120 >> GOOD MORNING, EVERYONE. 4801 02:54:37,120 --> 02:54:38,640 SO I'VE HAD BREAST CANCER, I WAS 4802 02:54:38,640 --> 02:54:40,040 DIAGNOSED IN 1998. 4803 02:54:40,040 --> 02:54:45,560 I HAD A MA STET A MASTECTOT 4804 02:54:45,560 --> 02:54:47,160 RECONSTRUCTION ALONG WITH 4805 02:54:47,160 --> 02:54:48,760 CHEMOTHERAPY, RADIATION, AND 4806 02:54:48,760 --> 02:54:51,000 BONE MARROW TRANSPLANT. 4807 02:54:51,000 --> 02:54:53,400 SO I'VE GONE THROUGH A LOT AND 4808 02:54:53,400 --> 02:54:54,600 I'VE HAD LYMPHEDEMA FOR MANY 4809 02:54:54,600 --> 02:54:55,800 YEARS. 4810 02:54:55,800 --> 02:54:58,240 AND SO THE IMPACT THAT IT'S HAD 4811 02:54:58,240 --> 02:55:03,280 ON ME HAS BEEN VARIED OVER THE 4812 02:55:03,280 --> 02:55:03,600 YEARS. 4813 02:55:03,600 --> 02:55:05,280 ONE OF MY MAIN CONCERNS IS JUST 4814 02:55:05,280 --> 02:55:09,840 ABOUT A LACK OF EDUCATION IN THE 4815 02:55:09,840 --> 02:55:13,120 MEDICAL COMMUNITY AND WITH 4816 02:55:13,120 --> 02:55:14,680 PATIENT SUFFERING FROM 4817 02:55:14,680 --> 02:55:15,520 LYMPHEDEMA, TO HAVE INFORMATION 4818 02:55:15,520 --> 02:55:17,080 TO BE EMPOWERED TO SEEK 4819 02:55:17,080 --> 02:55:17,960 EFFECTIVE TREATMENT. 4820 02:55:17,960 --> 02:55:18,360 >> GREAT. 4821 02:55:18,360 --> 02:55:20,440 THANK YOU. 4822 02:55:20,440 --> 02:55:22,840 MEX WE'LL GO TO CAM AYAL. 4823 02:55:22,840 --> 02:55:26,360 A. 4824 02:55:26,360 --> 02:55:26,560 ALA. 4825 02:55:26,560 --> 02:55:28,800 >> GOOD MORNING, GOOD AFTERNOON, 4826 02:55:28,800 --> 02:55:29,880 WHEREVER YOU'RE VIEWING FROM. 4827 02:55:29,880 --> 02:55:32,640 SO MY NAME IS CAM AYALA. 4828 02:55:32,640 --> 02:55:33,040 I'M 33. 4829 02:55:33,040 --> 02:55:35,640 OH, GOODNESS, I'M ACTUALLY 34. 4830 02:55:35,640 --> 02:55:36,960 SO 34 YEARS OLD. 4831 02:55:36,960 --> 02:55:39,600 AND I WAS BORN WITH PRIMARY 4832 02:55:39,600 --> 02:55:41,560 LYMPHEDEMA, BUT I STARTED 4833 02:55:41,560 --> 02:55:43,680 PRESENTING WITH THE SWELLING 4834 02:55:43,680 --> 02:55:44,720 SYMPTOMS PREDOMINANTLY IN MY 4835 02:55:44,720 --> 02:55:46,560 RIGHT LEG WHEN I WAS ABOUT 11 4836 02:55:46,560 --> 02:55:47,720 YEARS OLD. 4837 02:55:47,720 --> 02:55:50,440 SO SIMILAR TO CYNTHIA IN THE 4838 02:55:50,440 --> 02:55:51,640 SENSE THAT KIND OF AROUND THE 4839 02:55:51,640 --> 02:55:54,040 SAME TIME PERIOD, WE'VE BEEN 4840 02:55:54,040 --> 02:55:57,360 MANAGING OUR LYMPHEDEMA, THOUGH 4841 02:55:57,360 --> 02:55:58,840 HERS IS SECONDARY TO HER CANCER 4842 02:55:58,840 --> 02:56:01,800 BATTLE AND MIME IS PRIMARY TO BE 4843 02:56:01,800 --> 02:56:03,240 BORN WITH IT, WE HAVE A LOT OF 4844 02:56:03,240 --> 02:56:04,880 THE SAME OR SIMILAR DAILY 4845 02:56:04,880 --> 02:56:06,040 STRUGGLES AND CHALLENGES FROM 4846 02:56:06,040 --> 02:56:07,880 MANAGING THE CONDITION TO 4847 02:56:07,880 --> 02:56:09,440 ACCESSIBILITY TO SOME OF THE TOP 4848 02:56:09,440 --> 02:56:12,640 CARE PROVIDERS, WHETHER IT'S A 4849 02:56:12,640 --> 02:56:13,640 LYMPHEDEMA THERAPIST OR 4850 02:56:13,640 --> 02:56:15,800 PHYSICIANS WHO CAN HELP TREAT 4851 02:56:15,800 --> 02:56:16,720 LYMPHATIC DISEASE. 4852 02:56:16,720 --> 02:56:17,520 SO LOOKING FORWARD TO HEARING 4853 02:56:17,520 --> 02:56:19,240 THE REST OF THE PANELS AND 4854 02:56:19,240 --> 02:56:20,520 GIVING YOU GUYS SOME MORE 4855 02:56:20,520 --> 02:56:21,640 INFORMATION ABOUT EACH OF OUR 4856 02:56:21,640 --> 02:56:23,520 JOURNEYS AND WHAT WE HAVE AS A 4857 02:56:23,520 --> 02:56:25,200 CALL TO ACTION TO THE PEOPLE WHO 4858 02:56:25,200 --> 02:56:29,000 ARE VIEWING. 4859 02:56:29,000 --> 02:56:30,600 >> THANK YOU. 4860 02:56:30,600 --> 02:56:40,880 KASI GROSVENOR? 4861 02:57:26,720 --> 02:57:29,520 >> MY EXPERIENCE DID START AS A 4862 02:57:29,520 --> 02:57:33,920 TEENAGER. 4863 02:57:33,920 --> 02:57:34,520 I'VE REALLY STARTED NOTICING 4864 02:57:34,520 --> 02:57:38,400 THINGS LIKE SEVERE BRUISING IN S 4865 02:57:38,400 --> 02:57:40,600 WALKING WITH BLOCKS IN MY LEGS, 4866 02:57:40,600 --> 02:57:44,840 JUST A LOT OF PAIN WITH TOUCHING 4867 02:57:44,840 --> 02:57:45,880 AND SENSITIVITY AND THINGS LIKE 4868 02:57:45,880 --> 02:57:46,240 THAT. 4869 02:57:46,240 --> 02:57:49,280 EVEN WHEN I WOULD LOSE WEIGHT, I 4870 02:57:49,280 --> 02:57:50,400 WOULD ONLY LOSE WEIGHT ON THE 4871 02:57:50,400 --> 02:57:52,280 TOP HALF OF MY BODY. 4872 02:57:52,280 --> 02:57:54,160 I LOST 80 POUNDS AT ONE POINT 4873 02:57:54,160 --> 02:57:55,640 AND IT ONLY CHANGED MY LOWER 4874 02:57:55,640 --> 02:57:58,280 BODY BY ONE DRESS SIZE, AND 4875 02:57:58,280 --> 02:57:59,480 THAT'S PRETTY DRAMATIC FOR 4876 02:57:59,480 --> 02:58:01,120 80 POUNDS. 4877 02:58:01,120 --> 02:58:03,320 SO I HAVE REALLY STRUGGLED WITH 4878 02:58:03,320 --> 02:58:05,960 FINDING A DOCTOR THAT ACTUALLY 4879 02:58:05,960 --> 02:58:08,160 KNEW WHAT LIPEDEMA WAS, AND THAT 4880 02:58:08,160 --> 02:58:10,160 IS THE IMPORTANCE OF THIS 4881 02:58:10,160 --> 02:58:11,440 RESEARCH, THE MAJORITY OF 4882 02:58:11,440 --> 02:58:13,760 RESEARCH OUT THERE HAS REALLY 4883 02:58:13,760 --> 02:58:15,320 ONLY COME UP IN THE LAST FIVE 4884 02:58:15,320 --> 02:58:16,840 YEARS, AND THAT HAS NOT FOLLOWED 4885 02:58:16,840 --> 02:58:18,360 THROUGH TO CLINICIANS IN A LOT 4886 02:58:18,360 --> 02:58:21,080 OF CASES. 4887 02:58:21,080 --> 02:58:23,120 SO I AM TREATING MY LYMPHEDEMA 4888 02:58:23,120 --> 02:58:24,480 RIGHT NOW WITH A NUMBER OF 4889 02:58:24,480 --> 02:58:25,600 CONSERVATIVE TREATMENTS AND HAVE 4890 02:58:25,600 --> 02:58:28,000 SEEN A LOT OF BENEFITS FROM 4891 02:58:28,000 --> 02:58:29,560 DOING THOSE THINGS. 4892 02:58:29,560 --> 02:58:31,840 IT HAS IMPROVED MY SYMPTOMS AND 4893 02:58:31,840 --> 02:58:34,120 I'VE ALSO STARTED WITH 4894 02:58:34,120 --> 02:58:36,480 LYMPHEDEMA SURGERY AT JOHNS 4895 02:58:36,480 --> 02:58:37,560 HOPKINS UNIVERSITY EARLIER THIS 4896 02:58:37,560 --> 02:58:38,320 YEAR. 4897 02:58:38,320 --> 02:58:39,840 THANK YOU ALL SO MUCH FOR 4898 02:58:39,840 --> 02:58:40,440 WELCOMING US. 4899 02:58:40,440 --> 02:58:40,960 >> GREAT. 4900 02:58:40,960 --> 02:58:43,000 THANK YOU, KASI. 4901 02:58:43,000 --> 02:58:46,320 NEXT WE HAVE TAYLOR LEWIS. 4902 02:58:46,320 --> 02:58:47,320 >> HI, EVERYONE. 4903 02:58:47,320 --> 02:58:49,600 THANK YOU FOR HAVING ME. 4904 02:58:49,600 --> 02:58:50,600 I AM 28 YEARS OLD. 4905 02:58:50,600 --> 02:58:52,760 I HAVE GENERALIZED LYMPHATIC 4906 02:58:52,760 --> 02:58:54,200 ANO, 4907 02:58:54,200 --> 02:58:57,160 ANOMALY, ONCE CALLED 4908 02:58:57,160 --> 02:58:57,600 ANGIOMATOSIS. 4909 02:58:57,600 --> 02:58:59,120 I WAS DIAGNOSED IN 2012 AT THE 4910 02:58:59,120 --> 02:59:00,760 AGE OF 17. 4911 02:59:00,760 --> 02:59:02,520 I HAD QUITE A BIT OF SYMPTOMS 4912 02:59:02,520 --> 02:59:03,160 GROWING UP. 4913 02:59:03,160 --> 02:59:04,840 I'D SAY THEY WERE PEAKING DURING 4914 02:59:04,840 --> 02:59:06,680 PUBERTY, WHICH WE'RE FINDING NOW 4915 02:59:06,680 --> 02:59:07,920 IS PRETTY TYPICAL WITH THE 4916 02:59:07,920 --> 02:59:09,640 HORMONE PATHWAYS, AND I WAS 4917 02:59:09,640 --> 02:59:12,040 EXPERIENCING A LOT OF BACK PAIN, 4918 02:59:12,040 --> 02:59:13,800 A LOT OF JUST GENERALIZED BONE 4919 02:59:13,800 --> 02:59:15,560 PAIN, G.I. ISSUES, AND I WAS 4920 02:59:15,560 --> 02:59:17,800 ALSO A COMPETITIVE TENNIS 4921 02:59:17,800 --> 02:59:19,840 PLAYER, SO A LOT OF THAT WAS 4922 02:59:19,840 --> 02:59:22,240 DISMISSED THROUGH MY DIAGNOSIS 4923 02:59:22,240 --> 02:59:25,880 PROCESS AS INJURIES FROM TENNIS, 4924 02:59:25,880 --> 02:59:28,360 SO AFTER ABOUT 10 YEARS OF 4925 02:59:28,360 --> 02:59:29,600 TRYING TO GET A DIAGNOSIS, I 4926 02:59:29,600 --> 02:59:32,480 ENDED UP AT STANFORD, AND WAS 4927 02:59:32,480 --> 02:59:34,320 ABLE TO GET DIAGNOSED THERE 4928 02:59:34,320 --> 02:59:36,000 THROUGH A FEW BIOPSIES, AND WAS 4929 02:59:36,000 --> 02:59:41,200 PUT ON A CLINICAL TRIAL, 4930 02:59:41,200 --> 02:59:42,080 SIROLYMUS AT THE TIME. 4931 02:59:42,080 --> 02:59:42,800 RESEARCH HAS BEEN A HUGE 4932 02:59:42,800 --> 02:59:44,760 COMPONENT TO MY CARE. 4933 02:59:44,760 --> 02:59:49,960 I'M NOW ON ALPALOCIB, THE 4934 02:59:49,960 --> 02:59:50,920 PIC3 INHIB, TO REALLY HOPING TO 4935 02:59:50,920 --> 02:59:52,400 BRING A MENTAL HEALTH AND 4936 02:59:52,400 --> 02:59:53,360 FERTILITY COMPONENT TO THE TALK 4937 02:59:53,360 --> 02:59:53,640 TODAY. 4938 02:59:53,640 --> 02:59:54,760 I'M LOOKING FORWARD TO SPEAKING 4939 02:59:54,760 --> 02:59:58,040 ON THAT AND JUST HOW LIFE HAS 4940 02:59:58,040 --> 03:00:02,800 KIND OF BEEN INCORPORATED IN MY 4941 03:00:02,800 --> 03:00:04,120 HEALTH AND IT'S SOMETHING THEAZ 4942 03:00:04,120 --> 03:00:07,560 THEAS EASY THAT'S 4943 03:00:07,560 --> 03:00:09,880 EASY TO FORGET BUT IMPORTANT FOR 4944 03:00:09,880 --> 03:00:10,080 US. 4945 03:00:10,080 --> 03:00:11,200 >> GREAT, THANK YOU SO MUCH. 4946 03:00:11,200 --> 03:00:13,160 I'M JUST GOING TO REALLY TRY AND 4947 03:00:13,160 --> 03:00:14,760 GET OUT OF THE WAY AND HAVE YOU 4948 03:00:14,760 --> 03:00:15,920 GUYS TALK AS MUCH AS POSSIBLE, 4949 03:00:15,920 --> 03:00:17,760 SO BILL AND I WILL SORT OF GO 4950 03:00:17,760 --> 03:00:21,640 BACK AND FORTH WITH SOME TOPICS 4951 03:00:21,640 --> 03:00:24,600 JUST TO PROMPT YOU, BUT I WAS, I 4952 03:00:24,600 --> 03:00:26,360 THINK, MOST INTERESTED IN 4953 03:00:26,360 --> 03:00:27,760 KNOWING HOW YOUR DIFFERENT 4954 03:00:27,760 --> 03:00:30,840 DISEASES HAVE IMPACTED YOUR 4955 03:00:30,840 --> 03:00:32,160 LIFE, YOUR MENTAL HEALTH AND 4956 03:00:32,160 --> 03:00:33,360 FINANCIALLY WHAT'S BEEN THE 4957 03:00:33,360 --> 03:00:34,600 FINANCIAL IMPLICATIONS OF IT, 4958 03:00:34,600 --> 03:00:40,840 AND JUST HOW DOES IT -- HOWL ISS 4959 03:00:40,840 --> 03:00:42,280 TO LIVE SORT OF DAY TO DAY. 4960 03:00:42,280 --> 03:00:44,560 I THINK THAT WILL HELP THE 4961 03:00:44,560 --> 03:00:46,240 SCIENTISTS AND CLINICIANS THAT 4962 03:00:46,240 --> 03:00:47,720 ARE HERE TO UNDERSTAND WHY WE'RE 4963 03:00:47,720 --> 03:00:48,080 DOING THIS. 4964 03:00:48,080 --> 03:00:49,400 WHY DON'T WE START IN REVERSE 4965 03:00:49,400 --> 03:00:53,920 WITH TAYLOR AND THEN WE'LL GO. 4966 03:00:53,920 --> 03:00:55,840 >> SO I DEFINITELY SAY IN THE 4967 03:00:55,840 --> 03:00:58,160 EARLY STAGES AS A TEENAGER, I 4968 03:00:58,160 --> 03:01:00,880 WOULD SAY MY QUALITY OF LIFE 4969 03:01:00,880 --> 03:01:02,760 BECAME VERY IMPORTANT TO ME 4970 03:01:02,760 --> 03:01:03,640 BEFORE UNDERSTANDING THE 4971 03:01:03,640 --> 03:01:04,840 IMPORTANCE OF TAKING CARE OF 4972 03:01:04,840 --> 03:01:06,920 MYSELF. 4973 03:01:06,920 --> 03:01:08,240 I THINK THAT'S VERY MUCH THE 4974 03:01:08,240 --> 03:01:09,800 MINDSET A LOT OF TEENAGERS HAVE, 4975 03:01:09,800 --> 03:01:12,560 AND PEDIATRIC ONCOLOGY, AND IT 4976 03:01:12,560 --> 03:01:15,280 WAS INTRODUCED TO ME, THE OPTION 4977 03:01:15,280 --> 03:01:20,080 OF TAKING INTERFERON, AND AS A 4978 03:01:20,080 --> 03:01:21,280 17-YEAR-OLD GIRL GETTING READY 4979 03:01:21,280 --> 03:01:22,800 TO GO TO COLLEGE, THE THOUGHT OF 4980 03:01:22,800 --> 03:01:24,400 LOSING MY HAIR QUITE HONESTLY 4981 03:01:24,400 --> 03:01:25,440 WAS DEVASTATING TO ME. 4982 03:01:25,440 --> 03:01:27,960 I DON'T FEEL LIKE AT THE TIME 4983 03:01:27,960 --> 03:01:29,520 PEOPLE QUITE UNDERSTOOD WHAT 4984 03:01:29,520 --> 03:01:31,600 THAT WOULD HAVE MEANT FOR MY 4985 03:01:31,600 --> 03:01:33,880 LIFE IN COLLEGE, FOR MY SOCIAL 4986 03:01:33,880 --> 03:01:35,400 RELATIONSHIPS, FOR JUST ME 4987 03:01:35,400 --> 03:01:39,240 COPING IN A WHOLE NEW 4988 03:01:39,240 --> 03:01:41,000 ENVIRONMENT IS WHAT REALLY GOT 4989 03:01:41,000 --> 03:01:43,960 ME INTERESTED IN SIROLYM US, THE 4990 03:01:43,960 --> 03:01:45,160 OPPORTUNITY TO HAVE A DRUG THAT 4991 03:01:45,160 --> 03:01:46,200 WOULDN'T MAKE ME LOOK LIKE A 4992 03:01:46,200 --> 03:01:46,600 SICK PERSON. 4993 03:01:46,600 --> 03:01:48,360 IF YOU SEE ME ON THE STREET, I 4994 03:01:48,360 --> 03:01:50,480 LOOK HEALTHY, I LOOK FINE, BUT 4995 03:01:50,480 --> 03:01:54,080 INTERNALLY, THERE'S A LOT GOING 4996 03:01:54,080 --> 03:01:56,000 ON, THERE'S REALLY BESIDES MY 4997 03:01:56,000 --> 03:01:57,400 BRAIN A PLACE THAT MY DISEASE 4998 03:01:57,400 --> 03:01:57,600 ISN'T. 4999 03:01:57,600 --> 03:01:58,800 SO IT WAS REALLY CHALLENGING FOR 5000 03:01:58,800 --> 03:02:00,360 ME TO EVEN KNOW WHERE TO REACH 5001 03:02:00,360 --> 03:02:02,200 OUT TO GIVEN IT'S A RARE 5002 03:02:02,200 --> 03:02:03,840 DISEASE, THERE REALLY WASN'T 5003 03:02:03,840 --> 03:02:06,080 SUPPORT GROUPS, THERE WASN'T 5004 03:02:06,080 --> 03:02:07,160 ANYTHING THAT I COULD REACH OUT 5005 03:02:07,160 --> 03:02:12,640 TO, SO I FELT REALLY ALONE. 5006 03:02:12,640 --> 03:02:16,240 IF WASN'T UNTIL I GOT COVID WHEN 5007 03:02:16,240 --> 03:02:19,440 MY DISEASE PROGRESSED WHERE 5008 03:02:19,440 --> 03:02:20,520 SIROLIMUS WAS NO LONGER WORKING. 5009 03:02:20,520 --> 03:02:23,280 I REALLY PUSHED MYSELF TO GET 5010 03:02:23,280 --> 03:02:24,360 MENTAL HEALTH TREATMENT, I WAS 5011 03:02:24,360 --> 03:02:25,720 IN PRETTY DEEP DEPRESSION, 5012 03:02:25,720 --> 03:02:27,200 DEALING WITH A LOT OF ANXIETY. 5013 03:02:27,200 --> 03:02:29,320 I'M SOMEBODY WHO CAN REALLY 5014 03:02:29,320 --> 03:02:30,520 KICKBACK AND KIND OF LET THINGS 5015 03:02:30,520 --> 03:02:32,280 GO, BUT THIS IS THE FIRST TIME I 5016 03:02:32,280 --> 03:02:34,760 REALLY STRUGGLED, WAS ABOUT 5017 03:02:34,760 --> 03:02:34,960 2020. 5018 03:02:34,960 --> 03:02:36,880 SO ENDED UP GETTING SOME MENTAL 5019 03:02:36,880 --> 03:02:39,600 HEALTH TREATMENT, MEDICATION, 5020 03:02:39,600 --> 03:02:40,520 TREATMENT, THERAPY, AND IT'S 5021 03:02:40,520 --> 03:02:41,600 REALLY CHANGED MY LIFE. 5022 03:02:41,600 --> 03:02:46,520 IT'S MADE ME HAVE A WHOLE NEW 5023 03:02:46,520 --> 03:02:47,200 PERSPECTIVE. 5024 03:02:47,200 --> 03:02:49,840 I STARTED A PODCAST WITH MY RARE 5025 03:02:49,840 --> 03:02:51,120 DISEASE SISTER, IT'S OUR WAY OF 5026 03:02:51,120 --> 03:02:55,640 KIND OF GIVING OUT MENTAL HEALTH 5027 03:02:55,640 --> 03:02:56,480 UNDERSTANDING AND TO HIGHLIGHT 5028 03:02:56,480 --> 03:02:57,520 THE IMPORTANCE OF IT THAT I 5029 03:02:57,520 --> 03:03:04,960 THINK WE ALL NEED. 5030 03:03:04,960 --> 03:03:07,280 >> I LOVE YOUR STORY, TRACY. 5031 03:03:07,280 --> 03:03:08,960 I WANT TO JUMP TO CYNTHIA. 5032 03:03:08,960 --> 03:03:11,000 SOME OF THE THINGS WE HEAR ALL 5033 03:03:11,000 --> 03:03:11,800 THE TIME FROM PEOPLE WHO CALL 5034 03:03:11,800 --> 03:03:14,880 OUR OFFICE, ESPECIALLY THOSE WHO 5035 03:03:14,880 --> 03:03:18,240 HAVE CANCER, WELL, THEY CURED 5036 03:03:18,240 --> 03:03:19,800 YOUR CANCER, DON'T COMPLAIN. 5037 03:03:19,800 --> 03:03:21,120 THAT'S THE APPROACH PEOPLE HAVE 5038 03:03:21,120 --> 03:03:22,320 ENDED UP TAKING BECAUSE THEY'VE 5039 03:03:22,320 --> 03:03:23,520 FELT SO ISOLATED. 5040 03:03:23,520 --> 03:03:25,080 CYNTHIA, YOU'RE A GREAT ADVOCATE 5041 03:03:25,080 --> 03:03:25,560 AT THIS POINT. 5042 03:03:25,560 --> 03:03:27,280 I'M WONDERING WHAT YOUR JOURNEY 5043 03:03:27,280 --> 03:03:28,680 WAS AT YOUR POINT WHEN YOU FIRST 5044 03:03:28,680 --> 03:03:30,080 WENT THROUGH THE CANCER 5045 03:03:30,080 --> 03:03:31,120 DIAGNOSIS, AND THEN ENDED UP 5046 03:03:31,120 --> 03:03:32,760 FINDING OUT THAT YOU HAD 5047 03:03:32,760 --> 03:03:33,080 LYMPHEDEMA. 5048 03:03:33,080 --> 03:03:33,680 >> OKAY. 5049 03:03:33,680 --> 03:03:35,480 SO THANKS FOR THAT QUESTION, 5050 03:03:35,480 --> 03:03:35,680 BILL. 5051 03:03:35,680 --> 03:03:37,520 SO WHEN I FIRST WAS DIAGNOSED 5052 03:03:37,520 --> 03:03:38,760 WITH BREAST CANCER, OF COURSE 5053 03:03:38,760 --> 03:03:41,720 IT'S THE SCARIEST THING EVER, 5054 03:03:41,720 --> 03:03:43,000 AND THEN FINDING OUT MY BREAST 5055 03:03:43,000 --> 03:03:46,000 CANCER WAS AT STAGE III WAS EVEN 5056 03:03:46,000 --> 03:03:47,400 SCARIER, ESPECIALLY BEING THE 5057 03:03:47,400 --> 03:03:51,800 PARENT OF TWO YOUNG BOYS. 5058 03:03:51,800 --> 03:03:54,440 SO IT WAS KIND OF LIKE WHAT'S 5059 03:03:54,440 --> 03:03:58,840 THE MOST IMPORTANT THING HERE? 5060 03:03:58,840 --> 03:04:00,080 FIGHTING THE DISEASE, GEARING UP 5061 03:04:00,080 --> 03:04:01,360 FOR THAT AND MAKING SURE THAT 5062 03:04:01,360 --> 03:04:02,320 YOUR CHILDREN ARE GOOD. 5063 03:04:02,320 --> 03:04:04,880 LYMPHEDEMA WAS JUST SOMETHING 5064 03:04:04,880 --> 03:04:06,640 THAT WAS ALWAYS PUT ON THE BACK 5065 03:04:06,640 --> 03:04:07,600 BURNER. 5066 03:04:07,600 --> 03:04:08,920 FOR ONE, I LIVE IN NEW YORK 5067 03:04:08,920 --> 03:04:10,680 CITY, AND AT THE TIME THERE WAS 5068 03:04:10,680 --> 03:04:15,840 ONLY ONE PROVIDER THAT TREATED 5069 03:04:15,840 --> 03:04:16,000 IT. 5070 03:04:16,000 --> 03:04:16,760 AND IT WASN'T COVERED BY 5071 03:04:16,760 --> 03:04:17,040 INSURANCE. 5072 03:04:17,040 --> 03:04:18,800 SO BEING A YOUNG PARENT, I JUST 5073 03:04:18,800 --> 03:04:20,160 DIDN'T HAVE THE MONEY TO COVER 5074 03:04:20,160 --> 03:04:22,000 WHAT I NEEDED TO GET THE 5075 03:04:22,000 --> 03:04:24,960 TREATMENT, SO I WAS GIVEN A 5076 03:04:24,960 --> 03:04:27,080 PRESCRIPTION FOR A GARMENT, I 5077 03:04:27,080 --> 03:04:28,040 WORE IT, DIDN'T REALIZE THAT IT 5078 03:04:28,040 --> 03:04:29,520 WAS HELPING BY MAINTAINING THE 5079 03:04:29,520 --> 03:04:34,400 SIZE OF MY ARM. 5080 03:04:34,400 --> 03:04:35,600 AND THOUGHT IT'S NOT HELPING, MY 5081 03:04:35,600 --> 03:04:38,400 ARM ISN'T GET GETTING ANY SMAR 5082 03:04:38,400 --> 03:04:41,400 AND I CAN'T KEEP AFFORDING TO 5083 03:04:41,400 --> 03:04:42,800 SPEND MONEY ON THIS SO I STOPPED 5084 03:04:42,800 --> 03:04:44,600 WEARING T WHICH WAS THE WORST 5085 03:04:44,600 --> 03:04:46,080 DECISION EVER, BUT PART OF THAT 5086 03:04:46,080 --> 03:04:46,760 DECISION IS BECAUSE I DIDN'T 5087 03:04:46,760 --> 03:04:50,240 HAVE AND WASN'T GIVEN 5088 03:04:50,240 --> 03:04:51,640 INFORMATION ABOUT, YOU KNOW, HOW 5089 03:04:51,640 --> 03:04:55,600 TO TREAT AND MAINTAIN THE 5090 03:04:55,600 --> 03:04:55,920 LYMPHEDEMA. 5091 03:04:55,920 --> 03:05:00,080 SO I THINK BEING A SINGLE PARENT 5092 03:05:00,080 --> 03:05:03,440 AT THE TIME, FIGHTING THE 5093 03:05:03,440 --> 03:05:04,800 DISEASE AT THE TIME IS OKAY, 5094 03:05:04,800 --> 03:05:06,000 WHAT'S MORE IMPORTANT. 5095 03:05:06,000 --> 03:05:08,120 THE MESSAGE THAT I GOT FROM 5096 03:05:08,120 --> 03:05:09,600 HEALTHCARE PROVIDERS WAS 5097 03:05:09,600 --> 03:05:10,720 BASICALLY THIS IS JUST SOMETHING 5098 03:05:10,720 --> 03:05:12,320 THAT YOU HAVE TO LIVE WITH. 5099 03:05:12,320 --> 03:05:13,200 RIGHT? 5100 03:05:13,200 --> 03:05:16,400 SO -- AND IT WAS HARD TO ACCEPT. 5101 03:05:16,400 --> 03:05:21,760 BRU I BUT I JUST TOOK IT IN AS 5102 03:05:21,760 --> 03:05:23,360 SOMETHING I HAVE TO LIVE WITH, 5103 03:05:23,360 --> 03:05:23,840 JUST CHUCK IT UP. 5104 03:05:23,840 --> 03:05:25,720 >> ONE OF THE THINGS I FOUND SO 5105 03:05:25,720 --> 03:05:27,000 AMAZING IS NUMBER ONE SO MANY 5106 03:05:27,000 --> 03:05:27,920 PEOPLE COULD HAVE THE DISEASE 5107 03:05:27,920 --> 03:05:29,880 AND YET SO MANY OF THEM FEEL 5108 03:05:29,880 --> 03:05:32,320 ISOLATED AS IF THEY'RE THE ONLY 5109 03:05:32,320 --> 03:05:33,720 ONE IN THE WORLD THAT HAVE THIS 5110 03:05:33,720 --> 03:05:33,960 DISEASE. 5111 03:05:33,960 --> 03:05:34,440 >> YEAH. 5112 03:05:34,440 --> 03:05:35,840 THAT'S ACTUALLY A REALLY GOOD 5113 03:05:35,840 --> 03:05:36,880 POINT, BILL. 5114 03:05:36,880 --> 03:05:38,080 AND I WAS GOING TO ASK YOU, I 5115 03:05:38,080 --> 03:05:38,840 THINK -- I'M REQUESTING TO 5116 03:05:38,840 --> 03:05:40,680 DIRECT THIS QUESTION TO KASI BUT 5117 03:05:40,680 --> 03:05:42,240 ANYONE ELSE CAN ANSWER IT TOO. 5118 03:05:42,240 --> 03:05:46,120 A AWILL THERE'S A LOT OF 5119 03:05:46,120 --> 03:05:47,400 INFORMATION OUT THERE ON SOCIAL 5120 03:05:47,400 --> 03:05:48,720 NETWORKS AND THE INTERNET. 5121 03:05:48,720 --> 03:05:50,040 I THINK THAT COULD BE A GOOD OR 5122 03:05:50,040 --> 03:05:52,240 BAD THING. 5123 03:05:52,240 --> 03:05:55,360 MAYBE IT HELPS YOU SORT OF FIND 5124 03:05:55,360 --> 03:05:56,760 PEOPLE WHO ARE SIMILARLY 5125 03:05:56,760 --> 03:05:58,200 AFFECTED BUT MAYBE IT ALSO HAS 5126 03:05:58,200 --> 03:05:59,240 MENTAL HEALTH EFFECTS. 5127 03:05:59,240 --> 03:06:00,400 HOW HAS THAT HELPED YOU AND WHAT 5128 03:06:00,400 --> 03:06:05,720 DO YOU THINK THE IMPLICATIONS 5129 03:06:05,720 --> 03:06:05,880 ARE? 5130 03:06:05,880 --> 03:06:06,720 >> THANK YOU SO MUCH. 5131 03:06:06,720 --> 03:06:07,640 THAT IS SUCH AN IMPORTANT 5132 03:06:07,640 --> 03:06:08,680 SYMPTOM THAT I DID NOT MENTION, 5133 03:06:08,680 --> 03:06:12,200 IS THE MENTAL HEALTH COMPONENT. 5134 03:06:12,200 --> 03:06:13,320 THERE IS A PIECE OF ANXIETY THAT 5135 03:06:13,320 --> 03:06:15,600 COMES ALONG WITH HAVING A 5136 03:06:15,600 --> 03:06:16,360 CONDITION LIKE LYMPHEDEMA THAT 5137 03:06:16,360 --> 03:06:17,720 MOST PEOPLE WOULD NEVER 5138 03:06:17,720 --> 03:06:18,120 CONSIDER. 5139 03:06:18,120 --> 03:06:21,120 FOR EXAMPLE, WALKING INTO A 5140 03:06:21,120 --> 03:06:22,320 RESTAURANT AND SEEING THE CHAIRS 5141 03:06:22,320 --> 03:06:24,720 AND REALIZING, THEY'RE GOING TO 5142 03:06:24,720 --> 03:06:26,600 BE A TORTURE DEVICE AND I'M NOT 5143 03:06:26,600 --> 03:06:27,800 GOING TO MAKE IT THROUGH THIS 5144 03:06:27,800 --> 03:06:29,320 DINNER, I'M GOING TO HAVE TO 5145 03:06:29,320 --> 03:06:30,800 STAND BECAUSE I CANNOT SIT IN 5146 03:06:30,800 --> 03:06:31,800 THAT METAL CHAIR, OR WILL IT 5147 03:06:31,800 --> 03:06:32,720 HOLD ME. 5148 03:06:32,720 --> 03:06:35,120 THESE ARE THINGS LITERALLY EVERY 5149 03:06:35,120 --> 03:06:37,120 CHOICE THAT A WOMAN WITH 5150 03:06:37,120 --> 03:06:38,840 LYMPHEDEMA HAS TO GO THROUGH ON 5151 03:06:38,840 --> 03:06:40,240 A CONSTANT BASIS. 5152 03:06:40,240 --> 03:06:42,760 AND THE IMPORTANCE OF THOSE 5153 03:06:42,760 --> 03:06:45,320 SOCIAL NETWORKS, I WOULD SAY 5154 03:06:45,320 --> 03:06:46,680 HIGHLY OUTWEIGHS THE NEGATIVE 5155 03:06:46,680 --> 03:06:49,600 THINGS THAT YOU WILL RUN ACROSS. 5156 03:06:49,600 --> 03:06:52,520 I AM PART OF A GROUP OF WOMEN 5157 03:06:52,520 --> 03:06:57,320 THAT MEETS ON A MONTHLY BASIS 5158 03:06:57,320 --> 03:06:58,720 FOR A LYMPHEDEMA ROUNDTABLE, AND 5159 03:06:58,720 --> 03:07:00,120 THAT HAS BEEN REALLY ONE OF THE 5160 03:07:00,120 --> 03:07:01,440 BIGGEST THINGS THAT HAVE 5161 03:07:01,440 --> 03:07:04,280 IMPROVED MY MENTAL HEALTH SINCE 5162 03:07:04,280 --> 03:07:06,600 MY DIAGNOSIS. 5163 03:07:06,600 --> 03:07:07,680 LYMPHOPRESS IS A COMPANY THAT 5164 03:07:07,680 --> 03:07:09,440 MAKES A PNEUMATIC COMPRESSION 5165 03:07:09,440 --> 03:07:10,760 PUMP, AND THEY POST THAT FOR THE 5166 03:07:10,760 --> 03:07:11,760 PATIENTS. 5167 03:07:11,760 --> 03:07:14,200 I HAVE FOUND SO MUCH SUPPORT 5168 03:07:14,200 --> 03:07:16,480 FROM AN EMPATHETIC COMMUNITY OF 5169 03:07:16,480 --> 03:07:17,160 WOMEN THERE. 5170 03:07:17,160 --> 03:07:19,760 ON THE DOWNSIDE, THERE ARE 5171 03:07:19,760 --> 03:07:24,320 PEOPLE IN THE WORLD THAT 5172 03:07:24,320 --> 03:07:24,960 FETISHIZE DISEASES LIKE WHAT WE 5173 03:07:24,960 --> 03:07:26,200 HAVE, AND WE HAVE TO DEAL WITH A 5174 03:07:26,200 --> 03:07:29,160 LOT OF CREEPS, AND IT IS A DAILY 5175 03:07:29,160 --> 03:07:31,360 PART OF THE LIFE OF A WOMAN 5176 03:07:31,360 --> 03:07:32,560 LIVING WITH LYMPHEDEMA. 5177 03:07:32,560 --> 03:07:34,960 THAT ALSO IMPACT YOUR MENTAL 5178 03:07:34,960 --> 03:07:37,160 HEALTH, AND SO USING THOSE 5179 03:07:37,160 --> 03:07:40,000 SOCIAL NETWORKS TO FIND THE 5180 03:07:40,000 --> 03:07:40,920 EMPATHETIC WOMEN AND LEARN FROM 5181 03:07:40,920 --> 03:07:43,760 THEM AND TUNE OUT THE BAD HAS 5182 03:07:43,760 --> 03:07:47,400 BEEN A HUGE PART OF MY MOVING 5183 03:07:47,400 --> 03:07:48,400 FORWARD WITH LYMPHEDEMA. 5184 03:07:48,400 --> 03:07:50,680 >> GREAT. 5185 03:07:50,680 --> 03:07:53,240 HOW ABOUT IF I JUST JUMP TO CAM 5186 03:07:53,240 --> 03:07:54,240 BUT TO FOLLOW UP ON WHAT YOU'RE 5187 03:07:54,240 --> 03:07:56,080 SAYING, KASI, ONE THING I FOUND 5188 03:07:56,080 --> 03:07:57,080 INTERESTING, EVEN THOUGH THERE'S 5189 03:07:57,080 --> 03:07:58,760 FAR GREATER AWARENESS AT THIS 5190 03:07:58,760 --> 03:07:59,400 POINT, WE'RE STILL AT THE 5191 03:07:59,400 --> 03:08:00,320 BEGINNING OF GETTING WHERE WE 5192 03:08:00,320 --> 03:08:02,640 NEED TO GO, I FIND THAT WE GET 5193 03:08:02,640 --> 03:08:06,920 MORE CALLS TO OUR OFFICE AT 5194 03:08:06,920 --> 03:08:09,160 LE&RN NOW TALKING ABOUT SUICIDE 5195 03:08:09,160 --> 03:08:11,840 OR BODILY HARM THAN EVER BEFORE. 5196 03:08:11,840 --> 03:08:12,960 NOT BECAUSE MORE PEOPLE ARE 5197 03:08:12,960 --> 03:08:16,120 THINKING THAT, I JUST THINK 5198 03:08:16,120 --> 03:08:17,640 PEOPLE CAN ACTUALLY SPEAK ABOUT 5199 03:08:17,640 --> 03:08:20,720 THIS OUT LOUD. 5200 03:08:20,720 --> 03:08:22,320 BUT THAT'S OUR STARTING POINT. 5201 03:08:22,320 --> 03:08:25,080 AND THE MENTAL HEALTH PART OF IT 5202 03:08:25,080 --> 03:08:26,120 IS REALLY DRAMATIC. 5203 03:08:26,120 --> 03:08:28,560 I WANT TO TURN TO CAM AYALA. 5204 03:08:28,560 --> 03:08:30,200 CAM, YOU HAVE YOUR OWN REALLY 5205 03:08:30,200 --> 03:08:32,200 UNIQUE STORY, AND A RATHER 5206 03:08:32,200 --> 03:08:34,080 DRAMATIC ONE THAT PEOPLE MOST 5207 03:08:34,080 --> 03:08:35,520 OFTEN DON'T GO THROUGH WHEN IT 5208 03:08:35,520 --> 03:08:37,120 COMES TO LYMPHEDEMA, BUT IN YOUR 5209 03:08:37,120 --> 03:08:38,560 CASE, IT HAS, AND I'D LOVE FOR 5210 03:08:38,560 --> 03:08:41,320 YOU TO TALK A BIT ABOUT THAT AS 5211 03:08:41,320 --> 03:08:42,640 WELL, AND THE MENTAL HEALTH 5212 03:08:42,640 --> 03:08:44,000 ASPECTS OF WHAT GOES ALONG WITH 5213 03:08:44,000 --> 03:08:46,280 THAT ALSO. 5214 03:08:46,280 --> 03:08:48,240 >> YEAH. 5215 03:08:48,240 --> 03:08:49,640 AND TO GIVE BILL KIND OF A QUICK 5216 03:08:49,640 --> 03:08:51,240 SHOUT OUT HERE, A COUPLE MONTHS 5217 03:08:51,240 --> 03:08:53,760 AGO, HE RELEASED A PIECE ON 5218 03:08:53,760 --> 03:08:54,760 OUR -- ON THE LE&RN WEBSITE 5219 03:08:54,760 --> 03:08:55,800 ABOUT THE EMOTIONAL COMPONENTS 5220 03:08:55,800 --> 03:08:58,920 OF LIVING WITH LYMPHATIC 5221 03:08:58,920 --> 03:08:59,920 DISEASES, AND THAT'S ONE THING 5222 03:08:59,920 --> 03:09:02,160 THAT I FIND FASCINATING IN THE 5223 03:09:02,160 --> 03:09:04,480 UNITED STATES HEALTHCARE SYSTEM. 5224 03:09:04,480 --> 03:09:05,560 IN MOST STATES, A LOT OF 5225 03:09:05,560 --> 03:09:07,640 INSURANCE PROVIDERS REQUIRE A 5226 03:09:07,640 --> 03:09:10,120 PATIENT WHO'S GOING TO UNDERGO A 5227 03:09:10,120 --> 03:09:11,560 BARIATRIC SURGERY, FOR EXAMPLE, 5228 03:09:11,560 --> 03:09:17,440 TO GO THROUGH PSYCHOLOGICAL 5229 03:09:17,440 --> 03:09:18,080 EVALUATION BEFORE HAVING THAT 5230 03:09:18,080 --> 03:09:18,840 KIND OF SURGERY. 5231 03:09:18,840 --> 03:09:20,320 IN MY HUMBLE OPINION, I THINK 5232 03:09:20,320 --> 03:09:22,520 THAT'S A BIG OPPORTUNITY FOR ANY 5233 03:09:22,520 --> 03:09:23,600 TYPE OF LYMPHATIC DISEASE 5234 03:09:23,600 --> 03:09:25,160 PATIENT, IS TO HAVE THEIR CARE 5235 03:09:25,160 --> 03:09:27,360 PROVIDER, WHETHER IT'S THEIR 5236 03:09:27,360 --> 03:09:29,320 GENERAL PRACTITIONER, THEIR 5237 03:09:29,320 --> 03:09:30,080 ONCOLOGIST, LYMPHEDEMA 5238 03:09:30,080 --> 03:09:30,960 THERAPIST, WHOEVER IS PART OF 5239 03:09:30,960 --> 03:09:32,240 THEIR CARE TEAM, TO LET THEM 5240 03:09:32,240 --> 03:09:33,560 KNOW THAT, HEY, THERE'S AN 5241 03:09:33,560 --> 03:09:34,520 EMOTIONAL COMPONENT WITH THIS 5242 03:09:34,520 --> 03:09:35,720 DISEASE STATE BECAUSE IT IS 5243 03:09:35,720 --> 03:09:37,280 PROGRESSIVE IN NATURE, AND 5244 03:09:37,280 --> 03:09:38,080 CURRENTLY THERE'S NO CURE FOR 5245 03:09:38,080 --> 03:09:38,840 IT. 5246 03:09:38,840 --> 03:09:41,120 SO WHEN YOU GET THAT NEWS, THAT 5247 03:09:41,120 --> 03:09:43,520 REALITY THAT YOU'RE LIVING, YOU 5248 03:09:43,520 --> 03:09:45,000 MAY HAVE JUST WON YOUR CANCER 5249 03:09:45,000 --> 03:09:45,880 BATTLE BUT NOW YOU'RE GOING TO 5250 03:09:45,880 --> 03:09:47,960 HAVE A LIFELONG BATTLE WITH A 5251 03:09:47,960 --> 03:09:49,560 LYMPHATIC DISEASE, OR IF YOU'RE 5252 03:09:49,560 --> 03:09:51,800 LIKE ME IN MY CASE, WHERE I'VE 5253 03:09:51,800 --> 03:09:53,240 HAD ACCESSIBILITY TO SOME OF THE 5254 03:09:53,240 --> 03:09:55,160 TOP LYMPHATIC SPECIALISTS ACROSS 5255 03:09:55,160 --> 03:09:56,560 THE UNITED STATES, AND EVEN WITH 5256 03:09:56,560 --> 03:09:58,640 THAT ACCESSIBILITY, I 5257 03:09:58,640 --> 03:10:00,200 UNFORTUNATELY HAD TO LOSE MY 5258 03:10:00,200 --> 03:10:01,720 RIGHT LEG A COUPLE OF MONTHS AGO 5259 03:10:01,720 --> 03:10:04,160 DUE TO AMPUTATION BECAUSE OF 5260 03:10:04,160 --> 03:10:06,120 RECURRENCES OF INFECTION. 5261 03:10:06,120 --> 03:10:08,000 SO ABSOLUTELY, IT HAS IMPACTED 5262 03:10:08,000 --> 03:10:10,200 ME EMOTIONALLY FROM JUST MY 5263 03:10:10,200 --> 03:10:12,280 OVERALL BODY IMAGE, AND JUST 5264 03:10:12,280 --> 03:10:15,360 LIKE WITH THE ONLINE SPACE, YOU 5265 03:10:15,360 --> 03:10:16,560 KNOW, LIKE ANY MEDIA, YOU HAVE 5266 03:10:16,560 --> 03:10:17,920 TO TAKE THE GOOD AND THE BAD 5267 03:10:17,920 --> 03:10:19,160 BECAUSE THERE'S GOING TO BE A 5268 03:10:19,160 --> 03:10:21,360 LOT OF POSITIVITY ON THERE BUT 5269 03:10:21,360 --> 03:10:23,080 JUST AS MUCH NEGATIVITY, SO FOR 5270 03:10:23,080 --> 03:10:25,760 SOMEONE WHO MAY BE NEW TO THEIR 5271 03:10:25,760 --> 03:10:26,520 LYMPHATIC DISEASE DIAGNOSIS, I 5272 03:10:26,520 --> 03:10:28,400 WOULD SAY GO INTO DIFFERENT 5273 03:10:28,400 --> 03:10:29,680 SUPPORT GROUPS OR SOCIAL 5274 03:10:29,680 --> 03:10:31,440 PLATFORMS WITH AN OPEN MIND. 5275 03:10:31,440 --> 03:10:33,280 YOU DON'T NECESSARILY HAVE TO BE 5276 03:10:33,280 --> 03:10:34,640 A CONTENT CREATOR OR 5277 03:10:34,640 --> 03:10:36,520 CONTRIBUTOR, BUT YOU CAN STILL 5278 03:10:36,520 --> 03:10:38,040 CONSUME SOME OF THAT CONTENT, 5279 03:10:38,040 --> 03:10:40,520 AND OBVIOUSLY IF THERE'S ANY 5280 03:10:40,520 --> 03:10:41,720 ANECDOTES THAT'S EXPRESSED ON 5281 03:10:41,720 --> 03:10:42,960 SOCIAL PLATFORMS, MAKE SURE YOU 5282 03:10:42,960 --> 03:10:45,920 RUN THAT THROUGH YOUR CARE TEAM 5283 03:10:45,920 --> 03:10:47,800 AND REALLY BE YOUR OWN ADVOCATE. 5284 03:10:47,800 --> 03:10:49,120 AND THERE IS A LOT OF GREAT 5285 03:10:49,120 --> 03:10:50,760 SUPPORT ON THERE, BUT AGAIN, YOU 5286 03:10:50,760 --> 03:10:51,960 HAVE TO KIND OF WEIGH THE 5287 03:10:51,960 --> 03:10:53,440 POSITIVES AND NEGATIVES WITH 5288 03:10:53,440 --> 03:10:55,320 WHAT IS GOING TO HELP YOU KIND 5289 03:10:55,320 --> 03:10:56,760 OF DEAL WITH THE EMOTIONAL PART 5290 03:10:56,760 --> 03:10:58,840 AND THEN JUST GETTING THE RIGHT 5291 03:10:58,840 --> 03:10:59,640 INFORMATION AND RESOURCES 5292 03:10:59,640 --> 03:11:01,200 AVAILABLE SO YOU CAN HAVE A 5293 03:11:01,200 --> 03:11:04,160 BETTER QUALITY OF LIFE. 5294 03:11:04,160 --> 03:11:06,040 >> THANKS, CAM. 5295 03:11:06,040 --> 03:11:08,120 YOU KNOW, WHENEVER I SEE A 5296 03:11:08,120 --> 03:11:10,720 PATIENT WHO HAS A LOT OF 5297 03:11:10,720 --> 03:11:13,880 DIFFERENT SYMPTOMS OR ISSUES, I 5298 03:11:13,880 --> 03:11:16,360 ALWAYS TRY AND ASK THEM TO SORT 5299 03:11:16,360 --> 03:11:18,240 OF RANK WHAT ARE THE BIGGEST 5300 03:11:18,240 --> 03:11:20,600 PROBLEMS TO LOWEST PROBLEMS. 5301 03:11:20,600 --> 03:11:22,400 AND IN A PERFECT WORLD, WHAT 5302 03:11:22,400 --> 03:11:25,480 WOULD YOU WANT THE NIH OR 5303 03:11:25,480 --> 03:11:25,920 RESEARCHERS TO DO? 5304 03:11:25,920 --> 03:11:27,120 AND I THINK IF YOU CAN TRY AND 5305 03:11:27,120 --> 03:11:28,800 SORT OF RANK THAT, IT'S LIKE 5306 03:11:28,800 --> 03:11:30,560 WHAT'S THE MOST IMPORTANT THING 5307 03:11:30,560 --> 03:11:31,880 AND THEN WORK DOWN, THAT WOULD 5308 03:11:31,880 --> 03:11:33,960 BE REALLY GREAT. 5309 03:11:33,960 --> 03:11:35,320 I THINK ANY OF YOU CAN ANSWER. 5310 03:11:35,320 --> 03:11:40,800 MAYBE WE'LL START WITH TAYLOR. 5311 03:11:40,800 --> 03:11:43,520 >> SO I THINK A LOT OF THIS IS 5312 03:11:43,520 --> 03:11:45,440 BASED ON WHAT I'M FINDING, I'M 5313 03:11:45,440 --> 03:11:46,520 PROGRESSING THROUGH LIFE, JUST A 5314 03:11:46,520 --> 03:11:47,840 PERSONAL PIECE OF THIS. 5315 03:11:47,840 --> 03:11:49,520 I'M MARRIED AND MY HUSBAND AND I 5316 03:11:49,520 --> 03:11:55,640 ARE TRYING TO START A FAMILY, SO 5317 03:11:55,640 --> 03:11:56,840 WHAT THAT HAS LOOKED LIKE IS 5318 03:11:56,840 --> 03:11:58,480 MAKING SURE THAT MY MEDICATION 5319 03:11:58,480 --> 03:11:59,800 AND MY DISEASE IS STABLE TO 5320 03:11:59,800 --> 03:12:05,840 WHERE I CAN DO SO, AND SO WE'VE 5321 03:12:05,840 --> 03:12:06,720 GONE THROUGH THAT PROCESS. 5322 03:12:06,720 --> 03:12:08,280 I WAS GOING TO FREEZE MY EGGS 5323 03:12:08,280 --> 03:12:09,960 FOR PRESERVATION TO USE. 5324 03:12:09,960 --> 03:12:13,760 BUT WE HAVE FOUND THAT MY JUST 5325 03:12:13,760 --> 03:12:14,880 FERTILITY IS FUNCTIONING LIKE A 5326 03:12:14,880 --> 03:12:17,640 50 TO 60-YEAR-OLD AND A LOT OF 5327 03:12:17,640 --> 03:12:18,720 THAT, WE BELIEVE, IS COMING DOWN 5328 03:12:18,720 --> 03:12:19,920 TO THE MEDICATIONS THAT I'VE 5329 03:12:19,920 --> 03:12:21,720 BEEN ON AND HOW LONG I'VE BEEN 5330 03:12:21,720 --> 03:12:22,840 ON THEM. 5331 03:12:22,840 --> 03:12:25,880 IT IS NOT NORMAL FOR ME AT 28 TO 5332 03:12:25,880 --> 03:12:33,280 HAVE THESE ISSUES, AND WE'RE 5333 03:12:33,280 --> 03:12:34,720 FINDING A LOT OF OTHER YOUNG 5334 03:12:34,720 --> 03:12:35,800 WOMEN ON THE SAME MEDICATIONS 5335 03:12:35,800 --> 03:12:38,160 ARE STRUGGLING WITH THE SAME 5336 03:12:38,160 --> 03:12:39,000 THINGS. 5337 03:12:39,000 --> 03:12:39,880 SO IT'S EITHER THE DISEASE OR 5338 03:12:39,880 --> 03:12:42,040 THE MEDICATION BUT IT'S NOT JUST 5339 03:12:42,040 --> 03:12:42,400 A COINCIDENCE. 5340 03:12:42,400 --> 03:12:44,440 SO I THINK TALKING ABOUT 5341 03:12:44,440 --> 03:12:46,920 FERTILITY EARLY ON IS INCREDIBLY 5342 03:12:46,920 --> 03:12:47,680 IMPORTANT FOR THOSE WITH 5343 03:12:47,680 --> 03:12:48,360 LYMPHATIC DISEASE. 5344 03:12:48,360 --> 03:12:49,840 GIVEN THE PROGRESSION OF MY 5345 03:12:49,840 --> 03:12:52,120 DISEASE, I CAN'T CARRY A CHILD 5346 03:12:52,120 --> 03:12:53,480 WITH MY SPINE INVOLVEMENT, AND 5347 03:12:53,480 --> 03:12:55,200 IT REALLY NEVER WAS TALKED ABOUT 5348 03:12:55,200 --> 03:12:56,440 WITH ME AT ALL. 5349 03:12:56,440 --> 03:12:59,080 THE ONLY TIME IT WAS WAS THE DAY 5350 03:12:59,080 --> 03:13:00,800 I ARRIVED ON THE ONCOLOGY UNIT 5351 03:13:00,800 --> 03:13:02,160 FROM THE EMERGENCY ROOM WHEN I 5352 03:13:02,160 --> 03:13:03,800 WAS 17 YEARS OLD. 5353 03:13:03,800 --> 03:13:05,120 AND IT WAS 3:00 A.M. AND THE 5354 03:13:05,120 --> 03:13:06,640 DOCTOR CAME IN, THERE WAS LIKE 5355 03:13:06,640 --> 03:13:08,360 12 DOCTORS THAT CAME IN THAT DAY 5356 03:13:08,360 --> 03:13:09,760 AND ONE SAID, DO YOU WANT TO 5357 03:13:09,760 --> 03:13:11,400 FREEZE YOUR EGGS? 5358 03:13:11,400 --> 03:13:13,680 WE'RE CONSIDERING PUTTING YOU ON 5359 03:13:13,680 --> 03:13:14,200 CHEMOTHERAPY. 5360 03:13:14,200 --> 03:13:16,520 AND AT 17, I HAD NO AWARENESS 5361 03:13:16,520 --> 03:13:18,680 ABOUT WHAT ANY OF THAT MEANT. 5362 03:13:18,680 --> 03:13:21,360 I WAS IN SHOCK. 5363 03:13:21,360 --> 03:13:23,120 I WAS ON MORPHINE, SO NOT 5364 03:13:23,120 --> 03:13:25,760 THINKING RATIONALLY, AS WE KNOW. 5365 03:13:25,760 --> 03:13:27,400 AND MY MOM WASN'T EVEN IN THE 5366 03:13:27,400 --> 03:13:30,840 ROOM FOR THAT DECISION, SO I 5367 03:13:30,840 --> 03:13:32,920 FELT LIKE THERE'S BEEN A PIECE 5368 03:13:32,920 --> 03:13:34,320 OF THAT THAT'S BEEN TAKEN AWAY 5369 03:13:34,320 --> 03:13:35,720 FROM ME. 5370 03:13:35,720 --> 03:13:37,240 I DO KNOW THAT THERE'S A LOT OF 5371 03:13:37,240 --> 03:13:44,000 OPTIONS FOR MYSELF MOVING 5372 03:13:44,000 --> 03:13:45,320 FORWARD, BUT WHERE I THINK 5373 03:13:45,320 --> 03:13:47,200 THINGS NEED TO BE IS WE'RE 5374 03:13:47,200 --> 03:13:48,200 TALKING TO OUR YOUNG PATIENTS 5375 03:13:48,200 --> 03:13:49,600 ABOUT THEIR FER TELL, STARTING 5376 03:13:49,600 --> 03:13:53,240 AT FERTILITY STARTING 5377 03:13:53,240 --> 03:13:54,840 AT THE AGE 8 OR 10. 5378 03:13:54,840 --> 03:13:56,440 I DON'T THINK IT'S TOO EARLY, 5379 03:13:56,440 --> 03:13:57,640 THERE'S EVEN SOME INTERVENTIONS 5380 03:13:57,640 --> 03:13:59,520 WHERE YOU CAN REMOVE AN OVARY 5381 03:13:59,520 --> 03:14:01,080 AND PUT IT BACK IN WHEN THE 5382 03:14:01,080 --> 03:14:05,120 CHILD IS READY TO BEAR. 5383 03:14:05,120 --> 03:14:06,720 BUT I THINK ALL IN ALL, THAT'S 5384 03:14:06,720 --> 03:14:08,000 AN AREA THAT IS JUST SO 5385 03:14:08,000 --> 03:14:09,200 OVERLOOKED, IS OUR QUALITY OF 5386 03:14:09,200 --> 03:14:15,280 LIFE WITH FERTILITY, AND I WOULD 5387 03:14:15,280 --> 03:14:15,960 REALLY LIKE THAT TO CHANGE. 5388 03:14:15,960 --> 03:14:18,000 >> SO MAYBE STUDYING HOW 5389 03:14:18,000 --> 03:14:20,760 TREATMENTS FOR LYMPHATIC 5390 03:14:20,760 --> 03:14:22,560 DISEASES CAN -- WHAT EFFECTS DO 5391 03:14:22,560 --> 03:14:24,520 THEY HAVE ON YOUR FERTILITY AND 5392 03:14:24,520 --> 03:14:27,240 ALSO JUST MAKING PHYSICIANS 5393 03:14:27,240 --> 03:14:28,840 AWARE THAT THIS IS IMPORTANT. 5394 03:14:28,840 --> 03:14:30,240 CYNTHIA, YOU'VE LIVED WITH THIS 5395 03:14:30,240 --> 03:14:30,880 TOO, RIGHT? 5396 03:14:30,880 --> 03:14:32,000 YOU HAD AN ISSUE WITH THIS AS 5397 03:14:32,000 --> 03:14:32,560 WELL. 5398 03:14:32,560 --> 03:14:34,040 WHAT ARE YOUR SORT OF -- WHAT'S 5399 03:14:34,040 --> 03:14:35,320 ON YOUR WISH LIST AND WHAT'S 5400 03:14:35,320 --> 03:14:36,480 YOUR THOUGHT ON FERTILITY? 5401 03:14:36,480 --> 03:14:38,560 >> SO I'LL GO BACK TO EDUCATION 5402 03:14:38,560 --> 03:14:42,080 AND TO KIND OF ECHO OFF OF WHAT 5403 03:14:42,080 --> 03:14:45,360 CAM AND TAYLOR JUST SAID. 5404 03:14:45,360 --> 03:14:49,880 I THINK JUST LETTING PHYSICIANS 5405 03:14:49,880 --> 03:14:53,720 KNOW WHAT SOME OF THE SYMPTOMS 5406 03:14:53,720 --> 03:14:54,680 ARE AND JUST MORE ABOUT 5407 03:14:54,680 --> 03:14:59,200 LYMPHEDEMA WOULD BE HELPFUL, 5408 03:14:59,200 --> 03:15:00,840 BECAUSE I DIDN'T KNOW ABOUT 5409 03:15:00,840 --> 03:15:02,000 FREEZING MY EGGS WHEN I WAS 5410 03:15:02,000 --> 03:15:03,320 DIAGNOSED, AND I WASN'T GIVEN 5411 03:15:03,320 --> 03:15:03,840 THAT OPTION. 5412 03:15:03,840 --> 03:15:06,480 SO I DID HAVE TWO CHILDREN, AND 5413 03:15:06,480 --> 03:15:08,080 THE MOST IMPORTANT THING FOR ME 5414 03:15:08,080 --> 03:15:09,600 AT THE TIME WASN'T THINKING 5415 03:15:09,600 --> 03:15:11,440 ABOUT HAVING MORE CHILDREN, WAS 5416 03:15:11,440 --> 03:15:13,080 BATTLING MY CANCER. 5417 03:15:13,080 --> 03:15:16,720 BUT IN A SUPPORT GROUP, I FOUND 5418 03:15:16,720 --> 03:15:17,960 OUT THERE WERE TWO WOMEN THAT 5419 03:15:17,960 --> 03:15:20,560 WERE THERE THAT WAS GETTING THE 5420 03:15:20,560 --> 03:15:21,760 OPPORTUNITY TO FREEZE THEIR EGGS 5421 03:15:21,760 --> 03:15:23,360 AND I'M THINKING, OKAY, WHY 5422 03:15:23,360 --> 03:15:24,640 WASN'T I GIVEN THAT INFORMATION? 5423 03:15:24,640 --> 03:15:27,560 SO I THINK THAT THERE'S JUST AN 5424 03:15:27,560 --> 03:15:30,280 INCONSISTENCY ON WHICH PROVIDERS 5425 03:15:30,280 --> 03:15:31,920 HAVE MORE INFORMATION THAN 5426 03:15:31,920 --> 03:15:34,840 OTHERS, AND I IN FACT HAD A 5427 03:15:34,840 --> 03:15:36,320 CONVERSATION LIKE TWO WEEKS AGO, 5428 03:15:36,320 --> 03:15:38,320 WHEN I SAW MY HEMATOLOGIST, WE 5429 03:15:38,320 --> 03:15:39,400 HAD A CONVERSATION ABOUT THIS, 5430 03:15:39,400 --> 03:15:42,040 JUST THE EDUCATION AS A WHOLE, 5431 03:15:42,040 --> 03:15:44,160 AND A LOT OF THE THINGS THAT SHE 5432 03:15:44,160 --> 03:15:46,360 KNOWS ABOUT MY TREATMENT IS 5433 03:15:46,360 --> 03:15:48,000 BECAUSE I'VE TOLD HER AND I 5434 03:15:48,000 --> 03:15:50,960 FILLED HER IN, AND A LOT OF THE 5435 03:15:50,960 --> 03:15:52,400 RESOURCES I GOT, I GOT IT ON MY 5436 03:15:52,400 --> 03:15:53,400 OWN. 5437 03:15:53,400 --> 03:15:56,760 BUT SHE AND I BOTH AGREED THAT 5438 03:15:56,760 --> 03:15:59,160 MORE PEOPLE INVOLVED IN THE 5439 03:15:59,160 --> 03:16:00,160 TREATMENT OF PATIENTS WITH 5440 03:16:00,160 --> 03:16:02,800 CANCER OR THAT HAVE HAD CANCER 5441 03:16:02,800 --> 03:16:04,800 NEED TO BE INFORMED ABOUT 5442 03:16:04,800 --> 03:16:06,000 LYMPHEDEMA AND SOME OF THE 5443 03:16:06,000 --> 03:16:07,240 SYMPTOMS AND THE TREATMENTS AND 5444 03:16:07,240 --> 03:16:08,200 SO FORTH. 5445 03:16:08,200 --> 03:16:10,400 AND ONE THING I WANT TO ADD IS, 5446 03:16:10,400 --> 03:16:12,720 LUCKILY THROUGH MY CONSTANT 5447 03:16:12,720 --> 03:16:13,920 RESEARCH AND LOOKING UP 5448 03:16:13,920 --> 03:16:16,120 DIFFERENT TREATMENTS ON WHAT WAS 5449 03:16:16,120 --> 03:16:20,280 OUT THERE IN STUDIES, I FOUND A 5450 03:16:20,280 --> 03:16:24,800 DOCTOR AT SLOAN KETTERING WHO 5451 03:16:24,800 --> 03:16:25,720 DID SURGERY FOR LYMPHEDEMA. 5452 03:16:25,720 --> 03:16:28,480 SO I HAD SURGERY LAST YEAR, I'VE 5453 03:16:28,480 --> 03:16:29,120 HAD LIPOSUCTION THERAPY, WHICH 5454 03:16:29,120 --> 03:16:31,640 IS GOING TO BE FOLLOWED BY A 5455 03:16:31,640 --> 03:16:33,200 LYMPH NODE TRANSFER, SO JUST TO 5456 03:16:33,200 --> 03:16:36,840 GO BACK, I'VE HAD 24 LYMPH NODES 5457 03:16:36,840 --> 03:16:38,280 REMOVED, 8 OF WHICH WERE 5458 03:16:38,280 --> 03:16:41,800 POSITIVE FOR CANCER, AND SO WHEN 5459 03:16:41,800 --> 03:16:45,480 I FOUND THIS DOCTOR, I GOT -- I 5460 03:16:45,480 --> 03:16:47,680 THINK IT WAS IN 2020, I GOT TO 5461 03:16:47,680 --> 03:16:49,640 SEE HIM AND I WAS EVALUATED AND 5462 03:16:49,640 --> 03:16:51,560 I WAS A CANDIDATE FOR SURGERY, 5463 03:16:51,560 --> 03:16:55,080 WHICH I HAD LAST AUGUST. 5464 03:16:55,080 --> 03:16:56,960 THE CHANGE IN MY LIFE, LIKE, 5465 03:16:56,960 --> 03:16:59,360 ABSOLUTELY CHANGED MY LIFE, AND 5466 03:16:59,360 --> 03:17:01,240 SO I'M THINKING, HOW LONG WAS 5467 03:17:01,240 --> 03:17:02,640 THIS OPTION OUT THERE? 5468 03:17:02,640 --> 03:17:03,880 LIKE I'VE BEEN GETTING TREATMENT 5469 03:17:03,880 --> 03:17:06,080 FOR SO MANY YEARS. 5470 03:17:06,080 --> 03:17:07,640 WHY WASN'T I CONTACTED OR 5471 03:17:07,640 --> 03:17:09,680 SOMETHING SAYING, HEY, YOU KNOW, 5472 03:17:09,680 --> 03:17:11,640 THIS IS SOMETHING NEW THAT'S OUT 5473 03:17:11,640 --> 03:17:14,040 THERE, YOU COULD BE A GOOD 5474 03:17:14,040 --> 03:17:15,080 CANDIDATE FOR IT AND WE WANT YOU 5475 03:17:15,080 --> 03:17:16,280 TO COME IN. 5476 03:17:16,280 --> 03:17:20,880 SO I THINK ACCESS OF INFORMATION 5477 03:17:20,880 --> 03:17:23,520 WOULD BE A MAJOR STEP. 5478 03:17:23,520 --> 03:17:25,960 >> SO PHYSICIAN EDUCATION, 5479 03:17:25,960 --> 03:17:26,920 ACCESS TO INFORMATION AND 5480 03:17:26,920 --> 03:17:27,280 FERTILITY. 5481 03:17:27,280 --> 03:17:28,040 BILL, GO AHEAD. 5482 03:17:28,040 --> 03:17:30,240 >> I'M JUST GOING TO JUMP TO 5483 03:17:30,240 --> 03:17:34,640 KASI AND THEN CAM AS WELL ON THE 5484 03:17:34,640 --> 03:17:35,160 SAME THING. 5485 03:17:35,160 --> 03:17:36,280 YOU HAVE AN OPPORTUNITY NOW, 5486 03:17:36,280 --> 03:17:38,400 THIS IS NIH'S CONFERENCE THAT 5487 03:17:38,400 --> 03:17:41,800 THEY ARE PUTTING ON. 5488 03:17:41,800 --> 03:17:43,560 HOW MUCH MONEY IS NIH 5489 03:17:43,560 --> 03:17:44,840 NECESSARILY SPENDING IN THESE 5490 03:17:44,840 --> 03:17:45,200 AREAS? 5491 03:17:45,200 --> 03:17:46,240 ARE YOU SATISFIED WITH THAT, 5492 03:17:46,240 --> 03:17:47,640 WOULD YOU LIKE TO SEE IT BE 5493 03:17:47,640 --> 03:17:48,440 MORE, WHAT DIRECTION WOULD YOU 5494 03:17:48,440 --> 03:17:49,720 HAVE THAT GO? 5495 03:17:49,720 --> 03:17:52,080 THE MEDICAL PROFESSION, WHAT IS 5496 03:17:52,080 --> 03:17:53,160 IT YOU FEEL THEY NEED TO KNOW 5497 03:17:53,160 --> 03:17:54,680 THAT YOU HAVE THIS OPPORTUNITY 5498 03:17:54,680 --> 03:17:57,800 NOW TO STARE AT THEM AND SAY 5499 03:17:57,800 --> 03:17:58,480 THIS IS WHAT YOU DON'T KNOW, 5500 03:17:58,480 --> 03:17:59,800 THIS IS WHAT YOU NEED TO KNOW 5501 03:17:59,800 --> 03:18:00,760 AND I'M HERE TO TELL YOU. 5502 03:18:00,760 --> 03:18:02,360 I JUST WANT TO GIVE YOU THESE 5503 03:18:02,360 --> 03:18:03,880 LAST FEW MINUTES WE HAVE HERE, 5504 03:18:03,880 --> 03:18:06,800 FIRST YOU KASI, STRAIGHTFORWARD, 5505 03:18:06,800 --> 03:18:09,560 SAY IT RIGHT OUT, WHAT IS IT YOU 5506 03:18:09,560 --> 03:18:11,160 WANT FROM THESE TWO MAJOR 5507 03:18:11,160 --> 03:18:11,400 GROUPS? 5508 03:18:11,400 --> 03:18:12,160 >> ABSOLUTELY. 5509 03:18:12,160 --> 03:18:13,160 BILL, THANK YOU SO MUCH. 5510 03:18:13,160 --> 03:18:14,760 I WANT INVESTMENT IN RESEARCH 5511 03:18:14,760 --> 03:18:16,600 AND LYMPHEDEMA AND I THINK THE 5512 03:18:16,600 --> 03:18:19,640 NUMBER ONE GAP IS PROVIDING A 5513 03:18:19,640 --> 03:18:20,720 CLINICAL TEST THAT ANY DOCTOR 5514 03:18:20,720 --> 03:18:24,560 CAN FEEL CONFIDENT TELLING A 5515 03:18:24,560 --> 03:18:25,640 PATIENT, YES, YOU HAVE 5516 03:18:25,640 --> 03:18:25,920 LYMPHEDEMA. 5517 03:18:25,920 --> 03:18:27,680 I THINK THAT IS THE PRIMARY 5518 03:18:27,680 --> 03:18:29,080 PROBLEM FOR WOMEN BECAUSE MOST 5519 03:18:29,080 --> 03:18:30,960 OF US ARE NOT DIAGNOSED UNTIL 5520 03:18:30,960 --> 03:18:34,320 MUCH LATER IN LIFE WHEN EARLY 5521 03:18:34,320 --> 03:18:35,720 INTERVENTION HAS SHOWN A HUGE 5522 03:18:35,720 --> 03:18:38,040 IMPROVEMENT IN OUR QUALITY OF 5523 03:18:38,040 --> 03:18:38,240 LIFE. 5524 03:18:38,240 --> 03:18:40,360 A LOT OF PATIENTS AREN'T EVEN 5525 03:18:40,360 --> 03:18:42,360 GETTING DIAGNOSED UNTIL THE 5526 03:18:42,360 --> 03:18:43,560 LATER STAGES AND CERTAINLY LATER 5527 03:18:43,560 --> 03:18:46,400 IN LIFE, AND YOU GET DIMINISHING 5528 03:18:46,400 --> 03:18:48,400 RETURNS WITH CONSERVATIVE 5529 03:18:48,400 --> 03:18:49,480 TREATMENTS AS THEY GET FURTHER 5530 03:18:49,480 --> 03:18:49,680 ALONG. 5531 03:18:49,680 --> 03:18:52,600 THAT WOULD BE MY NUMBER ONE 5532 03:18:52,600 --> 03:18:52,800 GOAL. 5533 03:18:52,800 --> 03:18:54,800 MY NUMBER TWO GOAL FOR THE NIH 5534 03:18:54,800 --> 03:18:56,880 WOULD BE, LET'S GO BACK TO THE 5535 03:18:56,880 --> 03:18:58,040 RESEARCH THAT YOU'RE ALREADY 5536 03:18:58,040 --> 03:18:59,480 DOING AND LOOK FOR LYMPHEDEMA, 5537 03:18:59,480 --> 03:19:02,600 BECAUSE IT'S IN THERE IN THEIR 5538 03:19:02,600 --> 03:19:02,840 STUDIES. 5539 03:19:02,840 --> 03:19:03,880 IT MAY NOT HAVE BEEN CALLED THAT 5540 03:19:03,880 --> 03:19:05,960 OR IDENTIFIED AS THAT, FOR 5541 03:19:05,960 --> 03:19:08,320 EXAMPLE, COMORBIDITIES LIKE 5542 03:19:08,320 --> 03:19:10,320 ELERS DANLOS, AND YOU HAVE A LOT 5543 03:19:10,320 --> 03:19:16,640 OF PEOPLE OUT THERE THAT HAVE 5544 03:19:16,640 --> 03:19:17,520 MASS -- DISORDERS. 5545 03:19:17,520 --> 03:19:18,800 RECENTLY I WENT TO THE FAT 5546 03:19:18,800 --> 03:19:19,920 DISORDERS RESEARCH SOCIETY 5547 03:19:19,920 --> 03:19:21,000 CONFERENCE AND SEVERAL OF OUR 5548 03:19:21,000 --> 03:19:25,880 DOCTORS SPOKE ABOUT MAST CELL 5549 03:19:25,880 --> 03:19:27,040 EMBROADMENT AND YOU COULD 5550 03:19:27,040 --> 03:19:28,320 LITERALLY SEE EVERY PATIENT IN 5551 03:19:28,320 --> 03:19:30,240 THE ROOM SHAKING THEIR HEAD AND 5552 03:19:30,240 --> 03:19:31,440 THEY HAVE NO IDEA THEY'RE LIVING 5553 03:19:31,440 --> 03:19:33,400 WITH A MAST CELL DISORDER. 5554 03:19:33,400 --> 03:19:35,000 I HAVE FOUR PAGES OF WISH LIST 5555 03:19:35,000 --> 03:19:36,640 ITEMS IF YOU'D LIKE TO KNOW, BUT 5556 03:19:36,640 --> 03:19:38,160 IN THE INTEREST OF EVERYONE 5557 03:19:38,160 --> 03:19:39,760 ELSE'S TIME, I'LL PASS IT OVER 5558 03:19:39,760 --> 03:19:42,080 TO CAM TO ANSWER. 5559 03:19:42,080 --> 03:19:44,040 >> BELIEVE IT OR NOT, I'VE NEVER 5560 03:19:44,040 --> 03:19:46,040 HAD A COURSE IN MEDICAL SCHOOL 5561 03:19:46,040 --> 03:19:48,680 ON LYMPHEDEMA OR LYMPHATICS. 5562 03:19:48,680 --> 03:19:51,760 NOT EVEN A TOPIC THAT'S COVERED. 5563 03:19:51,760 --> 03:19:54,520 IT'S CRAZY TO ME. 5564 03:19:54,520 --> 03:19:54,680 CAM. 5565 03:19:54,680 --> 03:19:57,040 >> I WAS GOING TO SAY, MUCH LIKE 5566 03:19:57,040 --> 03:19:57,920 EVERYBODY ON THE PANEL, I THINK 5567 03:19:57,920 --> 03:19:59,760 WE HAVE A LONG LAUNDRY LIST OF 5568 03:19:59,760 --> 03:20:02,480 THINGS THAT WE WOULD LOVE TO SEE 5569 03:20:02,480 --> 03:20:03,800 ACCOMPLISHED IN OUR LIFETIME. 5570 03:20:03,800 --> 03:20:05,320 SO I WOULD KIND OF ECHO THE 5571 03:20:05,320 --> 03:20:08,040 SEPTEMBER IMENT OF E 5572 03:20:08,040 --> 03:20:10,280 SENTIMENT OF PRETTY MUCH EVERY 5573 03:20:10,280 --> 03:20:10,800 PANELIST AS WE UNDERSTAND 5574 03:20:10,800 --> 03:20:15,320 THERE'S SUCH A NEED DIRE NEER 5575 03:20:15,320 --> 03:20:16,960 RESEARCH ON THE LYMPHATIC SYSTEM 5576 03:20:16,960 --> 03:20:17,840 IN GENERAL. 5577 03:20:17,840 --> 03:20:19,920 EVEN IF YOU DON'T HAVE A LYMPH 5578 03:20:19,920 --> 03:20:20,760 DISEASE, WHATEVER CONTINUUM OF 5579 03:20:20,760 --> 03:20:21,960 PRESENTATION YOU HAVE, THERE'S 5580 03:20:21,960 --> 03:20:23,560 JUST A NEED IN GENERAL, BECAUSE 5581 03:20:23,560 --> 03:20:25,400 WE'RE STARTING TO UNDERSTAND THE 5582 03:20:25,400 --> 03:20:27,200 IMPLICATIONS OF THE LYMPHATIC 5583 03:20:27,200 --> 03:20:29,080 SYSTEM FOR OUR IMMUNE SYSTEM, 5584 03:20:29,080 --> 03:20:30,080 EARLY STAGES OF DEMENTIA, 5585 03:20:30,080 --> 03:20:31,640 THERE'S ALL THESE CORRELATIONS 5586 03:20:31,640 --> 03:20:33,240 THAT ARE THERE, THAT JUST 5587 03:20:33,240 --> 03:20:37,240 HAVEN'T BEEN PRIORITIZED IN THE 5588 03:20:37,240 --> 03:20:38,280 RESEARCH. 5589 03:20:38,280 --> 03:20:40,160 WORKING WITH LE&RN, THAT'S ONE 5590 03:20:40,160 --> 03:20:42,200 BENEFIT I HAVE, HAVING MY FINGER 5591 03:20:42,200 --> 03:20:43,680 ON THE PULSE OF THE COMMUNITY, 5592 03:20:43,680 --> 03:20:45,520 THE GLOBAL COMMUNITY, BUT 5593 03:20:45,520 --> 03:20:46,760 ESPECIALLY HERE IN THE UNITED 5594 03:20:46,760 --> 03:20:49,520 STATES, IT JUST BLOWS MY MIND 5595 03:20:49,520 --> 03:20:51,840 THAT WE CAN SEND A MAN OR WOMAN 5596 03:20:51,840 --> 03:20:54,040 TO THE MOON, BUT YET WE'RE STILL 5597 03:20:54,040 --> 03:20:56,000 WRAPPING UP PATIENTS LIKE 5598 03:20:56,000 --> 03:20:57,720 MUMMIES FOR THEIR COMPLETE 5599 03:20:57,720 --> 03:21:04,240 DEACON JESSTIVE THERAPY. 5600 03:21:04,240 --> 03:21:05,440 DECONGESTIVE THERAPY. 5601 03:21:05,440 --> 03:21:06,200 THERE'S GOT TO BE BETTER OPTION 5602 03:21:06,200 --> 03:21:08,920 FROM A DRUG OR THERAPY THAT CAN 5603 03:21:08,920 --> 03:21:09,680 SUBSTANTIALLY IMPROVE SYMPTOMS. 5604 03:21:09,680 --> 03:21:11,160 I'LL CLOSE WITH THIS. 5605 03:21:11,160 --> 03:21:13,080 I'VE BEEN FORTUNATE TO HAVE 5606 03:21:13,080 --> 03:21:14,120 ACCESSIBILITY TO SOME OF THE TOP 5607 03:21:14,120 --> 03:21:15,560 LYMPHATIC DOCTORS IN THE UNITED 5608 03:21:15,560 --> 03:21:17,080 STATES AND ARGUABLY THE WORLD, 5609 03:21:17,080 --> 03:21:18,920 AND EVEN WITH THAT 5610 03:21:18,920 --> 03:21:20,000 ACCESSIBILITY, FOR THEM TO TELL 5611 03:21:20,000 --> 03:21:21,120 ME THAT THEY'VE NEVER SEEN 5612 03:21:21,120 --> 03:21:23,120 ANOTHER PATIENT THAT HAS MY TYPE 5613 03:21:23,120 --> 03:21:24,400 OF PRESENTATION, THAT DOESN'T 5614 03:21:24,400 --> 03:21:26,000 REALLY LEAVE A SETTLING FEELING 5615 03:21:26,000 --> 03:21:27,280 IN MY STOMACH MOVING FORWARD 5616 03:21:27,280 --> 03:21:31,000 EERCHG AFTER THE 5617 03:21:31,000 --> 03:21:32,320 EVEN AFTER THE AMPUTATION OF 5618 03:21:32,320 --> 03:21:33,400 WHAT'S GOING TO HAPPEN THREE 5619 03:21:33,400 --> 03:21:34,920 YEARS FROM NOW, FIVE YEARS FROM 5620 03:21:34,920 --> 03:21:35,320 NOW. 5621 03:21:35,320 --> 03:21:36,320 REGARDLESS OF WHAT DISEASE YOU 5622 03:21:36,320 --> 03:21:37,520 HAVE AS A PATIENT, YOU DON'T 5623 03:21:37,520 --> 03:21:39,040 LIKE KNOWING THAT YOU'RE AN 5624 03:21:39,040 --> 03:21:39,240 UNKNOWN. 5625 03:21:39,240 --> 03:21:40,320 SO THAT DEFINITELY CAN ADD SOME 5626 03:21:40,320 --> 03:21:41,320 STRESS TO THE MENTAL HEALTH OF 5627 03:21:41,320 --> 03:21:42,840 IT AND JUST TRYING TO FIND A 5628 03:21:42,840 --> 03:21:44,000 BETTER QUALITY OF LIFE. 5629 03:21:44,000 --> 03:21:45,760 BUT WE KNOW THAT THE MONEY IS 5630 03:21:45,760 --> 03:21:47,400 THERE, IT JUST HAS TO BE 5631 03:21:47,400 --> 03:21:49,120 PRIORITIZED AND NOW IT'S UP FOR 5632 03:21:49,120 --> 03:21:50,520 ADVOCATES LIKE ALL THE PANELISTS 5633 03:21:50,520 --> 03:21:52,400 HERE AND GOING BACK TO OUR 5634 03:21:52,400 --> 03:21:54,360 COMMUNITIES AND RALLYING THOSE 5635 03:21:54,360 --> 03:21:56,120 TROOPS AND TO NOT BE IGNORED ANY 5636 03:21:56,120 --> 03:21:59,160 LONGER. 5637 03:21:59,160 --> 03:22:01,440 >> KASI, YOU MADE A REALLY GOOD 5638 03:22:01,440 --> 03:22:03,600 POINT ABOUT A DIAGNOSTIC TEST 5639 03:22:03,600 --> 03:22:04,040 FOR LYMPHEDEMA. 5640 03:22:04,040 --> 03:22:05,800 AND I THINK ALL OF YOU, WHEN YOU 5641 03:22:05,800 --> 03:22:09,720 WERE SORT OF TELLING US YOUR 5642 03:22:09,720 --> 03:22:10,920 STORIES, YOU TOLD US THAT 5643 03:22:10,920 --> 03:22:11,800 BASICALLY THE DIAGNOSIS WAS 5644 03:22:11,800 --> 03:22:15,200 EITHER DELAYED OR DEFERRED OR 5645 03:22:15,200 --> 03:22:15,520 MISTAKEN. 5646 03:22:15,520 --> 03:22:17,160 WHAT WERE THE EARLIEST SYMPTOMS 5647 03:22:17,160 --> 03:22:19,720 YOU HAD, AND HOW LATE DO YOU 5648 03:22:19,720 --> 03:22:20,840 THINK THE DIAGNOSIS WAS? 5649 03:22:20,840 --> 03:22:24,600 I MEAN, DID WE TOTALLY MISS THE 5650 03:22:24,600 --> 03:22:25,560 BOAT FOR ALL OF YOU? 5651 03:22:25,560 --> 03:22:28,320 >> MY SYMPTOMS BEGAN AS A 5652 03:22:28,320 --> 03:22:30,520 TEENAGER, AND I WAS GASLIGHTED 5653 03:22:30,520 --> 03:22:32,320 IN THE MEDICAL COMMUNITY UNTIL I 5654 03:22:32,320 --> 03:22:33,320 WAS 40 YEARS OLD. 5655 03:22:33,320 --> 03:22:36,160 IT TOOK ME TAKING A BROCHURE 5656 03:22:36,160 --> 03:22:37,200 FROM THE LYMPHEDEMA FOUNDATION 5657 03:22:37,200 --> 03:22:38,640 TO MY DOCTOR AND SITTING DOWN 5658 03:22:38,640 --> 03:22:40,800 AND SHOWING HER THE FACTS. 5659 03:22:40,800 --> 03:22:44,720 I HAVE REPORTED THESE SYMPTOMS 5660 03:22:44,720 --> 03:22:46,480 FOR 25 YEARS, AND I HAVE BEEN 5661 03:22:46,480 --> 03:22:48,800 TOLD CHRONICALLY, YOU ARE AN 5662 03:22:48,800 --> 03:22:50,600 OBESE WOMAN, THAT'S WHAT'S WRONG 5663 03:22:50,600 --> 03:22:51,400 WITH YOU. 5664 03:22:51,400 --> 03:22:53,880 I WAS NOT DIAGNOSED UNTIL 40, 5665 03:22:53,880 --> 03:22:55,960 AND I SELF-DIAGNOSED AND TOOK IN 5666 03:22:55,960 --> 03:22:58,360 MY DOCUMENTS AND CONVINCED MY 5667 03:22:58,360 --> 03:23:00,960 DOCTOR TO FINALLY GIVE ME A 5668 03:23:00,960 --> 03:23:02,080 DIAGNOSIS. 5669 03:23:02,080 --> 03:23:04,120 IT SHOULD NOT BE THAT LATE. 5670 03:23:04,120 --> 03:23:06,400 >> I WOULD SAY THAT I WAS 5671 03:23:06,400 --> 03:23:08,480 DIAGNOSED PRETTY EARLY ON, SO 5672 03:23:08,480 --> 03:23:11,640 RIGHT AFTER I COMPLETED 5673 03:23:11,640 --> 03:23:13,200 RADIATION THERAPY, WHICH WAS THE 5674 03:23:13,200 --> 03:23:14,400 LAST -- WELL, THE LAST PHASE OF 5675 03:23:14,400 --> 03:23:18,840 MY TREATMENT WAS ACTUALLY TAKING 5676 03:23:18,840 --> 03:23:20,240 THE DRUG TAMOXIFEN BUT PRIOR TO 5677 03:23:20,240 --> 03:23:22,400 THAT, IT WAS RADIATION. 5678 03:23:22,400 --> 03:23:23,480 EVEN THOUGH I WAS DIAGNOSED 5679 03:23:23,480 --> 03:23:25,040 EARLY, WAS HARD TO FIND A 5680 03:23:25,040 --> 03:23:26,960 PROVIDER FOR TREATMENT. 5681 03:23:26,960 --> 03:23:28,840 AND WHEN I DID FIND IT, I WOULD 5682 03:23:28,840 --> 03:23:32,440 HAVE TO PAY LIKE $2,000 OUT OF 5683 03:23:32,440 --> 03:23:34,200 POCKET, I HAD TO PAY FOR MY 5684 03:23:34,200 --> 03:23:37,520 CONSULTATION, HI TO I HAD TOR 5685 03:23:37,520 --> 03:23:40,560 MY GARMENTS, AND EVEN NOW THAT 5686 03:23:40,560 --> 03:23:41,760 THAT'S CHANGED, THERE'S STILL 5687 03:23:41,760 --> 03:23:44,080 NOT ENOUGH MONEY PUT INTO WHAT'S 5688 03:23:44,080 --> 03:23:45,840 NEEDED FOR A PATIENT TO MAINTAIN 5689 03:23:45,840 --> 03:23:47,200 THEIR LYMPHEDEMA. 5690 03:23:47,200 --> 03:23:49,200 SO I THINK THAT'S SOMETHING 5691 03:23:49,200 --> 03:23:50,280 THAT'S IMPORTANT THAT NEEDS TO 5692 03:23:50,280 --> 03:23:51,600 HAPPEN BECAUSE THIS IS SOMETHING 5693 03:23:51,600 --> 03:23:55,720 THAT'S NOT GOING AWAY, SO WHY AM 5694 03:23:55,720 --> 03:23:57,560 I ONLY ALLOWED TWO GARMENTS A 5695 03:23:57,560 --> 03:23:59,200 YEAR WHEN I HAVE TO SWITCH UP 5696 03:23:59,200 --> 03:24:00,840 BETWEEN TWO GARMENTS, AND THEN 5697 03:24:00,840 --> 03:24:03,480 EVENTUALLY, IF I CAN'T MAINTAIN 5698 03:24:03,480 --> 03:24:05,120 IT OR THE GARMENTS WEAR OUT, THE 5699 03:24:05,120 --> 03:24:07,040 LYMPHEDEMA IS GOING TO GET 5700 03:24:07,040 --> 03:24:07,680 WORSE. 5701 03:24:07,680 --> 03:24:09,640 SO INSURANCE COMPANIES NEED TO 5702 03:24:09,640 --> 03:24:11,600 BE -- NEED TO PROVIDE MORE 5703 03:24:11,600 --> 03:24:12,720 COVERAGE FOR CARE. 5704 03:24:12,720 --> 03:24:16,160 >> THAT'S INSANE. 5705 03:24:16,160 --> 03:24:17,600 WE DON'T HAVE TWO SHIRTS A YEAR, 5706 03:24:17,600 --> 03:24:19,080 I CAN'T IMAGINE HAVING TWO 5707 03:24:19,080 --> 03:24:19,680 GARMENTS A YEAR. 5708 03:24:19,680 --> 03:24:20,440 THAT'S KREADZ. 5709 03:24:20,440 --> 03:24:21,680 TAYLOR, WHAT ABOUT YOU? 5710 03:24:21,680 --> 03:24:23,360 >> SO I THINK JUST SOMETHING 5711 03:24:23,360 --> 03:24:27,040 THAT CAME UP IN THE CHAT TOO 5712 03:24:27,040 --> 03:24:27,880 THAT'S INTERESTING TO ME AND I 5713 03:24:27,880 --> 03:24:29,600 DIDN'T BRING IT UP EARLIER IS 5714 03:24:29,600 --> 03:24:31,680 THAT MY DISEASE IS ONLY TREATED 5715 03:24:31,680 --> 03:24:35,080 BY PEDIATRICS. 5716 03:24:35,080 --> 03:24:37,440 IN ARE NO ADULT DOCTORS IN THE 5717 03:24:37,440 --> 03:24:38,080 UNITED STATES THAT TREAT WHAT I 5718 03:24:38,080 --> 03:24:38,680 HAVE. 5719 03:24:38,680 --> 03:24:39,560 AND KIND OF GOING BACK TO A 5720 03:24:39,560 --> 03:24:43,000 LITTLE BIT OF WHAT CYNTHIA HAD 5721 03:24:43,000 --> 03:24:43,920 SAID ABOUT THE BURDEN OF JUST 5722 03:24:43,920 --> 03:24:45,560 TRAVEL, I TRAVEL FIVE HOURS EACH 5723 03:24:45,560 --> 03:24:49,040 WAY TO SEE MY PHYSICIAN. 5724 03:24:49,040 --> 03:24:50,840 IT'S INCREDIBLY EXPENSIVE. 5725 03:24:50,840 --> 03:24:52,720 I GO TO A CHILDREN'S HOSPITAL 5726 03:24:52,720 --> 03:24:55,120 AND SO FOLLOWING UP AND FINDING 5727 03:24:55,120 --> 03:24:57,120 EVEN JUST ADULT SPECIALISTS THAT 5728 03:24:57,120 --> 03:24:59,480 WILL WORK WITH MY ONCOLOGIST IS 5729 03:24:59,480 --> 03:25:02,320 INCREDIBLY CHALLENGING BECAUSE 5730 03:25:02,320 --> 03:25:03,440 PEOPLE DON'T KNOW WHAT I HAVE, 5731 03:25:03,440 --> 03:25:04,800 PEOPLE DON'T KNOW HOW TO TREAT 5732 03:25:04,800 --> 03:25:06,560 IT, AND OFTEN IT IS A BURDEN TO 5733 03:25:06,560 --> 03:25:09,200 THEM TO EVEN UNDERSTAND WHERE TO 5734 03:25:09,200 --> 03:25:12,040 GO WITH MY CASE. 5735 03:25:12,040 --> 03:25:13,080 >> CAM? 5736 03:25:13,080 --> 03:25:14,960 >> I WOULD SAY ONE THING THAT WE 5737 03:25:14,960 --> 03:25:16,720 ROUTINELY FIND, I MEAN, 5738 03:25:16,720 --> 03:25:17,880 CERTAINLY DOCTORS ARE BRILLIANT 5739 03:25:17,880 --> 03:25:19,200 PEOPLE AND THEY WANT TO COME 5740 03:25:19,200 --> 03:25:20,320 ACROSS AS BRILLIANT PEOPLE, BUT 5741 03:25:20,320 --> 03:25:21,560 IF YOU'RE A BRILLIANT PERSON AND 5742 03:25:21,560 --> 03:25:23,160 YOU DON'T KNOW HOW TO DIAGNOSE 5743 03:25:23,160 --> 03:25:25,280 OR TREAT SOMETHING, YOU HAVE TWO 5744 03:25:25,280 --> 03:25:27,280 CHOICES. 5745 03:25:27,280 --> 03:25:28,520 EITHER IT'S NOT THAT IMPORTANT 5746 03:25:28,520 --> 03:25:31,560 OR YOU'RE NOT A VERY GOOD 5747 03:25:31,560 --> 03:25:31,880 DOCTOR. 5748 03:25:31,880 --> 03:25:33,280 AND THE CHOICE WE GENERALLY FIND 5749 03:25:33,280 --> 03:25:34,920 IS THEY TEND TO MAKE YOU FEEL AS 5750 03:25:34,920 --> 03:25:36,440 IF YOUR DISEASE REALLY DOESN'T 5751 03:25:36,440 --> 03:25:37,760 DESERVE THE LEVEL OF ATTENTION 5752 03:25:37,760 --> 03:25:40,680 THAT YOU SEEM TO THINK THAT IT 5753 03:25:40,680 --> 03:25:41,680 DESERVES, BECAUSE THAT PUTS THEM 5754 03:25:41,680 --> 03:25:44,200 IN A BETTER POSITION. 5755 03:25:44,200 --> 03:25:46,160 AND I'M SURE ALL OF YOU HAVE 5756 03:25:46,160 --> 03:25:48,000 FOUND YOURSELF AT THE DOCTOR'S 5757 03:25:48,000 --> 03:25:49,640 OFFICES AND FINDING OUT AND 5758 03:25:49,640 --> 03:25:51,720 HAVING THEM EVEN SAY, YOU KNOW A 5759 03:25:51,720 --> 03:25:53,120 LOT MORE ABOUT THIS DISEASE THAN 5760 03:25:53,120 --> 03:25:54,960 I DO, AND I'VE LEARNED SO MUCH 5761 03:25:54,960 --> 03:25:55,640 FROM YOU. 5762 03:25:55,640 --> 03:25:56,960 AND THE FRUSTRATION THERE IS, 5763 03:25:56,960 --> 03:25:58,000 YOU DIDN'T GO TO THEM TO TEACH 5764 03:25:58,000 --> 03:25:59,200 THEM ABOUT THE DISEASE, YOU WENT 5765 03:25:59,200 --> 03:26:00,720 TO THEM TO BE TREATED FOR THE 5766 03:26:00,720 --> 03:26:01,160 DISEASE. 5767 03:26:01,160 --> 03:26:03,120 BUT THAT IS THE CASE WITH 5768 03:26:03,120 --> 03:26:03,440 MEDICINE. 5769 03:26:03,440 --> 03:26:04,520 AND IT'S NOT JUST IN THE UNITED 5770 03:26:04,520 --> 03:26:05,200 STATES. 5771 03:26:05,200 --> 03:26:06,680 I TRAVEL AROUND THE WORLD, AND 5772 03:26:06,680 --> 03:26:07,680 EVERY COUNTRY THROUGHOUT EUROPE, 5773 03:26:07,680 --> 03:26:09,000 ET CETERA, THE SAME THING IS 5774 03:26:09,000 --> 03:26:11,040 GOING ON WHEN IT COMES TO THIS 5775 03:26:11,040 --> 03:26:12,360 DISEASE, THESE DISEASES, 5776 03:26:12,360 --> 03:26:12,960 LYMPHATIC DISEASES. 5777 03:26:12,960 --> 03:26:15,640 >> AND I WAS GOING TO SAY, I 5778 03:26:15,640 --> 03:26:19,480 THINK -- I DON'T KNOW THIS FOR 5779 03:26:19,480 --> 03:26:22,080 SURE BUT I THINK A MAIN REASON 5780 03:26:22,080 --> 03:26:26,560 WHY DOCTORS GAS LIGHT PATIENTS 5781 03:26:26,560 --> 03:26:27,520 IS BECAUSE THEY DON'T KNOW. 5782 03:26:27,520 --> 03:26:28,520 INSTEAD OF SAYING I DON'T KNOW 5783 03:26:28,520 --> 03:26:30,120 WHAT'S WRONG WITH YOU, LET ME 5784 03:26:30,120 --> 03:26:32,000 LOOK FOR ANOTHER COLLEAGUE WHO 5785 03:26:32,000 --> 03:26:33,600 MIGHT KNOW, THEY SAY OH, IT'S 5786 03:26:33,600 --> 03:26:34,920 YOUR OBESITY OR WHATEVER IS AND 5787 03:26:34,920 --> 03:26:36,760 THEY SORT OF BLOW YOU OFF 5788 03:26:36,760 --> 03:26:37,600 BECAUSE THEY DON'T HAVE THE TIME 5789 03:26:37,600 --> 03:26:41,480 TO 50 FIND THE RIGHT PERSON 5790 03:26:41,480 --> 03:26:45,240 TO GO FIND THE RIGHT CONNECTION 5791 03:26:45,240 --> 03:26:47,320 TO GET YOU WITH. 5792 03:26:47,320 --> 03:26:48,880 THEY DON'T HAVE TIME TO HELP. 5793 03:26:48,880 --> 03:26:50,040 CAM, WHAT WERE YOU GOING TO SAY? 5794 03:26:50,040 --> 03:26:53,320 >> THIS KIND OF PIGGY BACKS ON 5795 03:26:53,320 --> 03:26:54,600 WHAT YOU WERE SAYING, AND BILL 5796 03:26:54,600 --> 03:26:55,240 AS WELL. 5797 03:26:55,240 --> 03:26:57,040 SO I WATCHED A LECTURE FROM A 5798 03:26:57,040 --> 03:26:58,280 PRETTY RENOWNED VASCULAR SURGEON 5799 03:26:58,280 --> 03:27:00,520 IN THE GREATER HOUSTON AREA 5800 03:27:00,520 --> 03:27:03,480 WHERE I'M FROM, AND HE EVEN GOT 5801 03:27:03,480 --> 03:27:07,200 HIS LYMPHEDEMA CERTIFICATION AT 5802 03:27:07,200 --> 03:27:10,440 THE GOLDI CLINIC IN GERMANY, ONE 5803 03:27:10,440 --> 03:27:11,120 OF THE TOP FACILITIES IN THE 5804 03:27:11,120 --> 03:27:12,760 WORLD FOR STUDYING AND TRAINING 5805 03:27:12,760 --> 03:27:13,960 PHYSICIANS AND THERAPISTS ON 5806 03:27:13,960 --> 03:27:17,560 LYMPHEDEMA TREATMENTS. 5807 03:27:17,560 --> 03:27:18,760 AND ONE OF THE POINTS HE MADE 5808 03:27:18,760 --> 03:27:20,080 FROM JUST A PURE BUSINESS 5809 03:27:20,080 --> 03:27:21,280 PERSPECTIVE IN THE UNITED STATES 5810 03:27:21,280 --> 03:27:24,080 IS, AS A VASCULAR SURGEON, HE 5811 03:27:24,080 --> 03:27:26,240 CAN DO A VEIN ABLATION, LIKE TWO 5812 03:27:26,240 --> 03:27:28,280 OR THREE OF THEM IN AN HOUR OR 5813 03:27:28,280 --> 03:27:29,520 TWO AND CHARGE THE INSURANCE A 5814 03:27:29,520 --> 03:27:31,960 COUPLE GRAND A POP, WHEREAS THE 5815 03:27:31,960 --> 03:27:34,360 COMPENSATION FOR TREATING ONE 5816 03:27:34,360 --> 03:27:38,720 LYMPHEDEMA PATIENT TO DO MANUAL 5817 03:27:38,720 --> 03:27:39,640 LYMPHATIC MASSAGE, THE 5818 03:27:39,640 --> 03:27:41,160 COMPENSATION FOR THAT IS LIKE A 5819 03:27:41,160 --> 03:27:41,680 COUPLE HUNDRED BUCKS. 5820 03:27:41,680 --> 03:27:43,440 SO FROM A PURE BUSINESS 5821 03:27:43,440 --> 03:27:45,160 PERSPECTIVE, A LOT OF THESE 5822 03:27:45,160 --> 03:27:46,400 DOCTORS ARE MAKING THEIR 5823 03:27:46,400 --> 03:27:47,920 DECISION BASED ON THEIR BOTTOM 5824 03:27:47,920 --> 03:27:48,240 LINE. 5825 03:27:48,240 --> 03:27:50,520 HOW CAN I MAKE MORE MONEY FROM 5826 03:27:50,520 --> 03:27:51,480 SEEING LESS PATIENTS, RIGHT? 5827 03:27:51,480 --> 03:27:53,360 AND SO THAT'S A SAD REALITY TOO, 5828 03:27:53,360 --> 03:27:54,680 JUST FROM THE INSURANCE 5829 03:27:54,680 --> 03:27:56,160 COMPENSATION, THAT AS A PATIENT, 5830 03:27:56,160 --> 03:27:57,280 IF YOUR INSURANCE DOESN'T COVER 5831 03:27:57,280 --> 03:27:59,680 THE TREATMENT, IT CAN BE VERY 5832 03:27:59,680 --> 03:28:01,400 EXPENSIVE AND THE DOCTORS AREN'T 5833 03:28:01,400 --> 03:28:02,160 NECESSARILY INCENTIVIZED IN A 5834 03:28:02,160 --> 03:28:06,760 LOT OF CASES BECAUSE FROM A 5835 03:28:06,760 --> 03:28:08,360 VENOUS PERSPECTIVE, THEY CAN 5836 03:28:08,360 --> 03:28:09,440 MAKE A LOT MORE MONEY DOING 5837 03:28:09,440 --> 03:28:14,160 VARIOUS OTHER TYPES OF VENOUS 5838 03:28:14,160 --> 03:28:16,160 PROCEDURES THAN IF YOU HAVE THE 5839 03:28:16,160 --> 03:28:17,280 LYMPHATIC DISEASE FIRST. 5840 03:28:17,280 --> 03:28:17,960 >> I THINK THAT'S SOMETHING THAT 5841 03:28:17,960 --> 03:28:19,440 CAN BE MANAGED FAIRLY 5842 03:28:19,440 --> 03:28:20,440 EXPEDITIOUSLY. 5843 03:28:20,440 --> 03:28:21,520 AT SLOAN KETTERING AND OTHER 5844 03:28:21,520 --> 03:28:23,680 PLACES WHERE WE WORK, WE USUALLY 5845 03:28:23,680 --> 03:28:25,760 GET DENIED FOR ANY LYMPHATIC 5846 03:28:25,760 --> 03:28:26,520 PROCEDURE WE DO. 5847 03:28:26,520 --> 03:28:28,160 WE DO THEM AND WE JUST SORT OF 5848 03:28:28,160 --> 03:28:28,400 EAT IT. 5849 03:28:28,400 --> 03:28:30,480 BUT WE GET DENIED 9 OUT OF 10. 5850 03:28:30,480 --> 03:28:31,880 AND I THINK WE COULD GO A VERY 5851 03:28:31,880 --> 03:28:33,840 LONG WAY IF MEDICARE STARTED TO 5852 03:28:33,840 --> 03:28:35,920 RECOGNIZE THESE PROCEDURES AS 5853 03:28:35,920 --> 03:28:38,320 NON-INVESTIGATIONAL. 5854 03:28:38,320 --> 03:28:40,600 SO LYMPHOVENOUS BYPASS, 5855 03:28:40,600 --> 03:28:42,160 LIPOSUCTION, THEY'RE ALL 5856 03:28:42,160 --> 03:28:43,080 CONSIDERED INVESTIGATIONAL FOR 5857 03:28:43,080 --> 03:28:43,960 THE TREATMENT OF LYMPHEDEMA AND 5858 03:28:43,960 --> 03:28:45,000 LYMPHEDEMA, BUT THEY'RE NOT. 5859 03:28:45,000 --> 03:28:46,400 THERE'S HUNDREDS OF PAPERS OUT 5860 03:28:46,400 --> 03:28:48,120 THERE THAT SHOW THAT THESE 5861 03:28:48,120 --> 03:28:49,280 TREATMENTS ARE EFFECTIVE. 5862 03:28:49,280 --> 03:28:51,480 YOU HEARD A VERY NICE TALK FROM 5863 03:28:51,480 --> 03:28:52,920 MARC TODAY AND ALSO FROM DHRUV, 5864 03:28:52,920 --> 03:28:55,000 BUT THE EVIDENCE IS PRETTY 5865 03:28:55,000 --> 03:28:56,600 OVERWHELMING, AND AT THIS POINT, 5866 03:28:56,600 --> 03:28:57,920 I THINK MEDICARE REALLY NEEDS TO 5867 03:28:57,920 --> 03:28:59,880 SORT OF STEP IN AND REG REC. 5868 03:28:59,880 --> 03:29:03,720 NIEZ THESE PROCEDURES, GIVING 5869 03:29:03,720 --> 03:29:05,120 THEM AN RVU AND I THINK OTHER 5870 03:29:05,120 --> 03:29:06,240 INSURANCE COMPANIES WILL FOLLOW. 5871 03:29:06,240 --> 03:29:07,360 BUT I THINK THIS IS SOMETHING 5872 03:29:07,360 --> 03:29:09,200 THAT COULD COME OUT FAIRLY 5873 03:29:09,200 --> 03:29:10,280 QUICKLY. 5874 03:29:10,280 --> 03:29:17,160 >> ONE THING I WANTED TO SAY, 5875 03:29:17,160 --> 03:29:18,560 DR. MEHRARA, YOU TALKED ABOUT 5876 03:29:18,560 --> 03:29:19,880 SOMETIMES DOCTORS DISMISSING 5877 03:29:19,880 --> 03:29:20,760 PATIENT BECAUSE THEY DON'T KNOW. 5878 03:29:20,760 --> 03:29:22,600 I WANT TO SAY SOME OF THE 5879 03:29:22,600 --> 03:29:23,920 DANGERS OF THAT, I'VE HAD 5880 03:29:23,920 --> 03:29:24,880 SEVERAL CELLULITIS INFECTIONS 5881 03:29:24,880 --> 03:29:26,760 WHERE I HAD TO BE HOSPITALIZED 5882 03:29:26,760 --> 03:29:27,720 MULTIPLE TIMES. 5883 03:29:27,720 --> 03:29:28,960 A LOT OF TIMES I GO IN, I KNOW 5884 03:29:28,960 --> 03:29:30,240 WHAT IT IS, I TELL THEM WHAT IT 5885 03:29:30,240 --> 03:29:32,200 IS, AND THEN WE GO FORWARD. 5886 03:29:32,200 --> 03:29:35,040 BUT I THINK THE PROBLEM IN 5887 03:29:35,040 --> 03:29:38,920 DOCTORS DOING THAT OR NOT 5888 03:29:38,920 --> 03:29:40,920 KNOWING WHAT CERTAIN THINGS CAN 5889 03:29:40,920 --> 03:29:42,560 LEAD TO IS THAT CELLULITIS 5890 03:29:42,560 --> 03:29:43,680 INFECTION CAN BE DEADLY. 5891 03:29:43,680 --> 03:29:46,840 SO YOU KNOW, YOU HAVE TO KNOW 5892 03:29:46,840 --> 03:29:48,160 ABOUT WHAT PEOPLE WITH 5893 03:29:48,160 --> 03:29:50,440 LYMPHEDEMA ARE COMING IN WITH, 5894 03:29:50,440 --> 03:29:55,480 SO THAT YOU CAN BE ABLE TO, I 5895 03:29:55,480 --> 03:29:57,600 GUESS, DIAGNOSE OR PROJECT A 5896 03:29:57,600 --> 03:30:00,640 GOOD COURSE OF TREATMENT. 5897 03:30:00,640 --> 03:30:01,400 >> I THINK THAT'S A GREAT 5898 03:30:01,400 --> 03:30:02,600 POIFNLT I ALWAYS TELL MY 5899 03:30:02,600 --> 03:30:04,440 RESIDENTS AND FELLOWS THAT NO 5900 03:30:04,440 --> 03:30:05,640 ONE COMES IN TO THE EMERGENCY 5901 03:30:05,640 --> 03:30:06,800 ROOM BECAUSE THEY WANT TO, NO 5902 03:30:06,800 --> 03:30:08,080 ONE IS FAKING PAIN OR WHATEVER. 5903 03:30:08,080 --> 03:30:09,040 THEY HAVE A PROBLEM. 5904 03:30:09,040 --> 03:30:10,680 AND JUST BECAUSE YOU CAN'T SEE 5905 03:30:10,680 --> 03:30:12,200 IT, IT DOESN'T MEAN IT'S NOT 5906 03:30:12,200 --> 03:30:13,280 THERE, BECAUSE THE SYMPTOMS 5907 03:30:13,280 --> 03:30:15,040 OFTEN APPEAR WAY BEFORE WE CAN 5908 03:30:15,040 --> 03:30:16,000 DIAGNOSE IT. 5909 03:30:16,000 --> 03:30:17,640 SO I THINK THAT'S A REALLY GOOD 5910 03:30:17,640 --> 03:30:18,400 POINT. 5911 03:30:18,400 --> 03:30:19,960 I THINK THAT'S A GREAT POINT. 5912 03:30:19,960 --> 03:30:23,200 BILL? 5913 03:30:23,200 --> 03:30:25,160 WE HAVE TWO MINUTES. 5914 03:30:25,160 --> 03:30:27,560 ANY LAST MINUTE QUESTIONS? 5915 03:30:27,560 --> 03:30:30,080 >> I WANT TO THANK THE PANEL, 5916 03:30:30,080 --> 03:30:30,960 TAKE A MOMENT TO SAY THAT. 5917 03:30:30,960 --> 03:30:32,840 AS I SAY, UP UNTIL A FEW YEARS 5918 03:30:32,840 --> 03:30:34,240 AGO, THIS KIND OF THING WASN'T 5919 03:30:34,240 --> 03:30:34,600 HAPPENING. 5920 03:30:34,600 --> 03:30:37,040 I WAS AT ONE RESEARCHER 5921 03:30:37,040 --> 03:30:38,280 CONFERENCE AND IT WAS THE FIRST 5922 03:30:38,280 --> 03:30:40,120 TIME THIS WAS EVER DONE, AND 5923 03:30:40,120 --> 03:30:41,120 RESEARCHERS CAME UP AND SAID, 5924 03:30:41,120 --> 03:30:42,400 GEE, I'VE BEEN DOING RESEARCH 5925 03:30:42,400 --> 03:30:44,040 FOR 20 YEARS, I'VE NEVER 5926 03:30:44,040 --> 03:30:45,360 ACTUALLY MET A PATIENT BEFORE. 5927 03:30:45,360 --> 03:30:47,440 AND AS A RESULT, THERE WAS THIS 5928 03:30:47,440 --> 03:30:49,200 HUGE DISCONNECT ABOUT THE 5929 03:30:49,200 --> 03:30:51,120 IMPORTANCE, BUT ALSO THE POWER 5930 03:30:51,120 --> 03:30:53,880 OF YOUR STORIES IN A WAY THAT IT 5931 03:30:53,880 --> 03:30:55,240 ACTUALLY DRIVES RESEARCHERS AND 5932 03:30:55,240 --> 03:30:56,840 PEOPLE IN THE MEDICAL PROFESSION 5933 03:30:56,840 --> 03:30:58,560 TO CREATE CHANGE, AND HOPEFULLY 5934 03:30:58,560 --> 03:31:00,880 NIH AS WELL, TO PUT MORE 5935 03:31:00,880 --> 03:31:02,840 RESOURCES AND MONEY INTO 5936 03:31:02,840 --> 03:31:04,800 LYMPHATIC RESEARCH, NOW WE'RE 5937 03:31:04,800 --> 03:31:05,640 DEVELOPING THE NATIONAL 5938 03:31:05,640 --> 03:31:07,240 COMMISSION HOPEFULLY AT NIH THAT 5939 03:31:07,240 --> 03:31:08,800 CONGRESS HAS CALLED FOR, WE LOOK 5940 03:31:08,800 --> 03:31:09,640 FORWARD HOPEFULLY THAT ALL OF 5941 03:31:09,640 --> 03:31:11,040 YOU WILL BE PART OF IT BECAUSE 5942 03:31:11,040 --> 03:31:13,520 YOU'RE THE ONES WITH THE REAL 5943 03:31:13,520 --> 03:31:15,080 INFORMATION THAT WE NEED TO PUT 5944 03:31:15,080 --> 03:31:16,480 FORWARD FOR THIS. 5945 03:31:16,480 --> 03:31:17,960 I CAN'T THANK YOU ENOUGH FOR 5946 03:31:17,960 --> 03:31:20,200 YOUR BRAVERY IN COMING FORWARD. 5947 03:31:20,200 --> 03:31:22,120 AND SPEAKING FOR EACH ONE OF 5948 03:31:22,120 --> 03:31:23,200 YOUR COMMUNITIES AND ALSO 5949 03:31:23,200 --> 03:31:24,640 DEALING WITH THE MENTAL HEALTH 5950 03:31:24,640 --> 03:31:26,600 ISSUE THAT I JUST FIND IS SO 5951 03:31:26,600 --> 03:31:27,880 IGNORED BECAUSE WE HAVE SO MANY 5952 03:31:27,880 --> 03:31:29,400 OTHER ISSUES ON TOP OF IT, THAT 5953 03:31:29,400 --> 03:31:34,000 WE ARE TRYING TO FIGHT FOR, BUT 5954 03:31:34,000 --> 03:31:35,560 TAYLOR, YOU BROUGHT THIS UP AND 5955 03:31:35,560 --> 03:31:37,200 HAVE SPOKEN BEFORE AND I REALLY 5956 03:31:37,200 --> 03:31:39,000 APPRECIATE IT, AND I APPRECIATED 5957 03:31:39,000 --> 03:31:39,560 ALL OF YOU HAVING THE 5958 03:31:39,560 --> 03:31:40,440 OPPORTUNITY TO SPEAK ON THAT 5959 03:31:40,440 --> 03:31:42,440 ISSUE AS WELL, BECAUSE THIS IS A 5960 03:31:42,440 --> 03:31:43,640 PRETTY DEVASTATING ONE. 5961 03:31:43,640 --> 03:31:45,680 >> YEAH, AND I WANT TO THANK YOU 5962 03:31:45,680 --> 03:31:46,880 TOO, BECAUSE IT'S REALLY HARD 5963 03:31:46,880 --> 03:31:49,000 TO, YOU KNOW, GET IN FRONT OF AN 5964 03:31:49,000 --> 03:31:50,280 AUDIENCE AND SHARE YOUR STORY, 5965 03:31:50,280 --> 03:31:51,520 BUT I THINK IT'S IMPORTANT. 5966 03:31:51,520 --> 03:31:53,200 I THINK PEOPLE NEED TO HEAR IT, 5967 03:31:53,200 --> 03:31:55,320 AND I THINK THEY NEED TO HEAR IT 5968 03:31:55,320 --> 03:31:56,280 FROM PATIENTS WHO HAVE 5969 03:31:56,280 --> 03:31:56,920 EXPERIENCED IT. 5970 03:31:56,920 --> 03:31:57,920 SO I REALLY WANT TO THANK YOU 5971 03:31:57,920 --> 03:32:02,160 FOR TAKING THE TIME TO DO IT. 5972 03:32:02,160 --> 03:32:03,480 >> THANK YOU SO MUCH. 5973 03:32:03,480 --> 03:32:05,000 >> WE HAVE SOME QUESTIONS BUT I 5974 03:32:05,000 --> 03:32:06,320 THINK MOST OF THEM WERE ANSWERED 5975 03:32:06,320 --> 03:32:08,600 IN THE Q & A, SO I THINK WE'LL 5976 03:32:08,600 --> 03:32:12,240 TAKE A BREAK AND THANK AGAIN 5977 03:32:12,240 --> 03:32:15,440 EVERYONE FOR JOINING US. 5978 03:32:15,440 --> 03:32:19,880 >> BABAK, CAN YOU PASS TO 5979 03:32:19,880 --> 03:32:20,440 PATRICIA, PLEASE? 5980 03:32:20,440 --> 03:32:22,720 >> YES, I'M GOING TO PASS IT -- 5981 03:32:22,720 --> 03:32:24,080 ACTUALLY WE'RE NOT TAKING A 5982 03:32:24,080 --> 03:32:24,280 BREAK. 5983 03:32:24,280 --> 03:32:25,480 DON'T TAKE A BREAK. 5984 03:32:25,480 --> 03:32:26,320 >> THANK YOU. 5985 03:32:26,320 --> 03:32:30,720 AM I GOING TO INTRODUCE NOWM OUW 5986 03:32:30,720 --> 03:32:32,720 OTHER NEXT SPEAKER, DR. REEMA 5987 03:32:32,720 --> 03:32:33,520 RAILKAR. 5988 03:32:33,520 --> 03:32:35,960 SCIENTIFIC PROGRAM MANAGER IN 5989 03:32:35,960 --> 03:32:36,640 THE NATIONAL CANCER INSTITUTE'S 5990 03:32:36,640 --> 03:32:40,400 SMALL BUSINESS INNOVATION 5991 03:32:40,400 --> 03:32:41,040 RESEARCH, SBIR, DEVELOPMENT 5992 03:32:41,040 --> 03:32:41,360 CENTER. 5993 03:32:41,360 --> 03:32:45,360 SHE WILL TALK ABOUT SBIR AND 5994 03:32:45,360 --> 03:32:46,720 SMALL BUSINESS TECHNOLOGY 5995 03:32:46,720 --> 03:32:47,800 TRANSFER, STTR, FUNDING 5996 03:32:47,800 --> 03:32:52,040 PROGRAMS. 5997 03:32:52,040 --> 03:32:52,240 REEMA? 5998 03:32:52,240 --> 03:32:54,280 >> CAN YOU HEAR ME? 5999 03:32:54,280 --> 03:32:55,280 I'M GOING TO CHANGE MY DISPLAY 6000 03:32:55,280 --> 03:32:55,560 SETTINGS. 6001 03:32:55,560 --> 03:32:56,680 I THINK THEY SHOULD BE BETTER. 6002 03:32:56,680 --> 03:32:57,200 >> YES. 6003 03:32:57,200 --> 03:33:03,040 >> FANTASTIC. 6004 03:33:03,040 --> 03:33:04,000 THANK YOU SO MUCH TO THE 6005 03:33:04,000 --> 03:33:05,080 ORGANIZERS AND MOST IMPORTANTLY 6006 03:33:05,080 --> 03:33:05,880 THANK YOU TO THE PATIENTS FOR 6007 03:33:05,880 --> 03:33:06,920 TELLING THEIR STORIES. 6008 03:33:06,920 --> 03:33:10,560 I WAS LISTENING AND THIS IS 6009 03:33:10,560 --> 03:33:11,880 REALLY IMPORTANT, I THINK IT IS 6010 03:33:11,880 --> 03:33:13,600 IMPORTANT NOT ONLY FOR THE 6011 03:33:13,600 --> 03:33:14,400 CLINICIANS AND RESEARCHERS WHO 6012 03:33:14,400 --> 03:33:16,600 ARE WORKING IN THIS AREA, BUT 6013 03:33:16,600 --> 03:33:19,200 ALSO FOR THE DIFFERENTLY 6014 03:33:19,200 --> 03:33:21,040 INSTITUTES OF NIH WHEN THEY ARE 6015 03:33:21,040 --> 03:33:22,920 THINKING ABOUT HAVING SOME 6016 03:33:22,920 --> 03:33:26,440 SPECIALIZED FUNDING OPPORTUNITY 6017 03:33:26,440 --> 03:33:30,360 ANNOUNCEMENTS TARGETED TOWARDS A 6018 03:33:30,360 --> 03:33:31,240 PARTICULAR DISEASE AREA. 6019 03:33:31,240 --> 03:33:33,560 SO I REALLY THANK ORGANIZERS AND 6020 03:33:33,560 --> 03:33:40,040 THE PATIENTS FOR THE TALKS 6021 03:33:40,040 --> 03:33:40,480 TODAY. 6022 03:33:40,480 --> 03:33:42,120 WHAT I'M GOING DO IS TALK A 6023 03:33:42,120 --> 03:33:45,360 LITTLE BIT ABOUT THE SBIR 6024 03:33:45,360 --> 03:33:48,440 FUNDING OPPORTUNITIES THAT ARE 6025 03:33:48,440 --> 03:33:49,440 NECESSARY, THE WAY YOU CAN 6026 03:33:49,440 --> 03:33:51,080 COMMERCIALIZE YOUR TECHNOLOGIES 6027 03:33:51,080 --> 03:33:53,240 FROM LAB TO MARKET FOR THE 6028 03:33:53,240 --> 03:33:54,880 BENEFIT OF PATIENTS, PROVIDERS 6029 03:33:54,880 --> 03:34:00,560 AND CAREGIVERS. 6030 03:34:00,560 --> 03:34:02,680 THE SBIR PROGRAM RUNS ACROSS 11 6031 03:34:02,680 --> 03:34:08,920 FEDERAL AGENCIES THAT INCLUDES 6032 03:34:08,920 --> 03:34:09,880 DEPARTMENT OF HEALTH AND HUMAN 6033 03:34:09,880 --> 03:34:11,600 SERVICES, AND NIH IS A PART OF 6034 03:34:11,600 --> 03:34:11,920 THIS AGENCY. 6035 03:34:11,920 --> 03:34:14,160 THE SBIR AND STTR PROGRAMS ARE 6036 03:34:14,160 --> 03:34:15,760 CONGRESSIONALLY MANDATED 6037 03:34:15,760 --> 03:34:16,320 SET-ASIDE PROGRAMS. 6038 03:34:16,320 --> 03:34:20,120 WHAT IT MEANS IS THAT THOSE 6039 03:34:20,120 --> 03:34:25,720 FEDERAL AGENCIES ARE ONLY 6040 03:34:25,720 --> 03:34:27,440 BUDGETED A CERTAIN AMOUNT SET 6041 03:34:27,440 --> 03:34:29,200 ASIDE PART OF THE BUDGET FOR 6042 03:34:29,200 --> 03:34:29,960 SBIR OR SMALL BUSINESS 6043 03:34:29,960 --> 03:34:32,680 INNOVATION RESEARCH, AND STTR, 6044 03:34:32,680 --> 03:34:35,880 OR SMALL BUSINESS TECHNOLOGY 6045 03:34:35,880 --> 03:34:36,720 TRANSFER PROGRAM. 6046 03:34:36,720 --> 03:34:40,000 NIH HAS $1.2 BILLION SET ASIDE 6047 03:34:40,000 --> 03:34:42,640 FOR THE SBIR/STTR FUNDING. 6048 03:34:42,640 --> 03:34:44,120 WITHIN NIH, THERE ARE 27 6049 03:34:44,120 --> 03:34:47,960 INSTITUTES AND CENTERS THAT ARE 6050 03:34:47,960 --> 03:34:49,960 DIVIDED BY EITHER DISEASE AREA 6051 03:34:49,960 --> 03:34:57,200 OR ORGAN OR PARTICULAR ACTIVITY. 6052 03:34:57,200 --> 03:35:00,240 23 OF THESE INSTITUTES UNTIL 6053 03:35:00,240 --> 03:35:04,560 PINK AND RED ARE THE -- ALTHOUGH 6054 03:35:04,560 --> 03:35:07,120 PARTS OF MY TALK ARE PRIMARILY 6055 03:35:07,120 --> 03:35:09,280 RELATED TO NCI OR NATIONAL CANS 6056 03:35:09,280 --> 03:35:12,120 SER NATIONAL 6057 03:35:12,120 --> 03:35:12,960 CANCER INSTITUTE, IF THERE ARE 6058 03:35:12,960 --> 03:35:14,760 OTHER AREAS YOU'RE INTERESTED IN 6059 03:35:14,760 --> 03:35:15,280 PLEASE LET ME KNOW. 6060 03:35:15,280 --> 03:35:16,320 WE ALL WORK COLLABORATIVELY HERE 6061 03:35:16,320 --> 03:35:18,520 AT NIH AND I'M HAPPY TO CONNECT 6062 03:35:18,520 --> 03:35:19,560 WITH THE APPROPRIATE PERSON 6063 03:35:19,560 --> 03:35:20,640 ACROSS THE INSTITUTES. 6064 03:35:20,640 --> 03:35:22,840 LET'S TALK ABOUT THE ELIGIBILITY 6065 03:35:22,840 --> 03:35:26,680 FOR THE SBIR/STTR PROGRAMS. 6066 03:35:26,680 --> 03:35:30,560 THE AWARD IS ALWAYS MADE TO A 6067 03:35:30,560 --> 03:35:33,800 SMALL BUSINESS CONCERN. 6068 03:35:33,800 --> 03:35:35,320 THE SMALL BUSINESS MUST BE 6069 03:35:35,320 --> 03:35:36,440 ORGANIZED FOR PROFIT IN THE 6070 03:35:36,440 --> 03:35:39,240 UNITED STATES WITH 500 OR FEWER 6071 03:35:39,240 --> 03:35:41,520 EMPLOYEES AND ASSOCIATES. 6072 03:35:41,520 --> 03:35:42,960 AND THIS SMALL BUSINESS 6073 03:35:42,960 --> 03:35:45,080 CONSULTANT MUST BE 50% OR MORE 6074 03:35:45,080 --> 03:35:49,960 OWNED BY U.S. INDIVIDUALS. 6075 03:35:49,960 --> 03:35:51,480 WHY SEEK SBIR/STTR FUNDING? 6076 03:35:51,480 --> 03:35:53,680 IT IS THE BIGGEST SOURCE OF SEED 6077 03:35:53,680 --> 03:35:55,160 FUNDING AVAILABLE TO SMALL 6078 03:35:55,160 --> 03:35:57,040 BUSINESSES IN THE BIOMEDICAL 6079 03:35:57,040 --> 03:35:57,520 FIELD. 6080 03:35:57,520 --> 03:36:00,200 THIS IS A GRANT AND NOT A LOAN, 6081 03:36:00,200 --> 03:36:03,200 WHICH MEANS THAT IT IS A 6082 03:36:03,200 --> 03:36:03,800 NON-DILUTIVE TYPE OF FUNDING. 6083 03:36:03,800 --> 03:36:05,600 IF YOU GENERATE ANY I.P. USING 6084 03:36:05,600 --> 03:36:07,760 THESE FUNDS, NIH DOES NOT CLAIM 6085 03:36:07,760 --> 03:36:11,040 THIS I.P.: SINCE APPLICATION 6086 03:36:11,040 --> 03:36:12,400 GOES THROUGH NIH REVIEW PROCESS, 6087 03:36:12,400 --> 03:36:14,520 IT PROVIDES VERIFICATION FOR 6088 03:36:14,520 --> 03:36:18,080 YOUR TECHNOLOGY, AND FINALLY 6089 03:36:18,080 --> 03:36:20,640 ANY -- HAVING THIS GRANT IN 6090 03:36:20,640 --> 03:36:24,480 ATTRACTING PRIVATE FUNDING SUCH 6091 03:36:24,480 --> 03:36:25,960 AS -- FUNDING. 6092 03:36:25,960 --> 03:36:26,640 SO WHAT IS THE DIFFERENCE 6093 03:36:26,640 --> 03:36:27,960 BETWEEN SBIR AND STTR, AND THIS 6094 03:36:27,960 --> 03:36:29,360 IS REALLY IMPORTANT FOR THE 6095 03:36:29,360 --> 03:36:34,400 ACADEMICS WHO ARE IN THIS GROUP. 6096 03:36:34,400 --> 03:36:35,840 THE STTR ESPECIALLY. 6097 03:36:35,840 --> 03:36:37,160 SO STTR PRIORS IT IS A MUST TO 6098 03:36:37,160 --> 03:36:39,200 HAVE A PARTNERSHIP BETWEEN THE 6099 03:36:39,200 --> 03:36:42,960 SMALL BUSINESSES AND A U.S. 6100 03:36:42,960 --> 03:36:44,600 NON-PROFIT RESEARCH INSTITUTION 6101 03:36:44,600 --> 03:36:46,800 SUCH AS UNIVERSITIES. 6102 03:36:46,800 --> 03:36:48,240 FOR SBIR, SUCH PARTNERSHIP IS 6103 03:36:48,240 --> 03:36:49,880 NOT NEEDED BUT IF YOU WANT TO 6104 03:36:49,880 --> 03:36:53,920 HAVE IT, YOU CAN HAVE IT. 6105 03:36:53,920 --> 03:36:55,200 ONE OF THE MOST IMPORTANT 6106 03:36:55,200 --> 03:36:56,320 DIFFERENCE BETWEEN SBIR AND 6107 03:36:56,320 --> 03:36:57,520 STTR, AND IT IS AGAIN REALLY 6108 03:36:57,520 --> 03:36:58,600 IMPORTANT FOR THE ACADEMICS WHO 6109 03:36:58,600 --> 03:37:03,960 ARE HERE, IS THAT PI'S PRIMARY 6110 03:37:03,960 --> 03:37:05,000 PLACE OF EMPLOYMENT. 6111 03:37:05,000 --> 03:37:08,680 IN CASE OF STTR, PRIMARY PLACE 6112 03:37:08,680 --> 03:37:10,560 OF EMPLOYMENT IS NOT STIPULATED 6113 03:37:10,560 --> 03:37:12,520 WHICH MEANS YOU CAN MAINTAIN 6114 03:37:12,520 --> 03:37:17,120 YOUR TENURED OR TENURED TRACK 6115 03:37:17,120 --> 03:37:18,520 POSITION AT A UNIVERSITY WHILE 6116 03:37:18,520 --> 03:37:20,080 HAVING AN STTR GRANT. 6117 03:37:20,080 --> 03:37:22,480 IN CASE OF SBIR, THOUGH, THE 6118 03:37:22,480 --> 03:37:23,680 P.I. MUST BE MORE THAN 50% 6119 03:37:23,680 --> 03:37:24,440 EMPLOYED AT THE SMALL BUSINESS 6120 03:37:24,440 --> 03:37:28,840 CONCERN. 6121 03:37:28,840 --> 03:37:30,680 THE SBIR/STTR PROGRAMS PROVIDE 6122 03:37:30,680 --> 03:37:36,920 THE FUNDING BASED ON MILESTONES 6123 03:37:36,920 --> 03:37:37,760 ACHIEVED DURING THE DIFFERENT 6124 03:37:37,760 --> 03:37:38,200 PHASES. 6125 03:37:38,200 --> 03:37:39,600 PLEASE DO NOT CONFUSE THEM WITH 6126 03:37:39,600 --> 03:37:40,600 THE PHASES OF CLINICAL TRIALS. 6127 03:37:40,600 --> 03:37:48,080 THESE ARE THE PHASES OF FUNDING. 6128 03:37:48,080 --> 03:37:56,280 SO YOU MAY SPHART START WIT, 6129 03:37:56,280 --> 03:37:58,560 PROVE OF CONCEPT, PHASE TWO IS 6130 03:37:58,560 --> 03:38:09,000 RESEARCH AND DEVELOPMENT. 6131 03:38:10,440 --> 03:38:12,000 ONLY FOR SBIR YOU CAN ALSO APPLY 6132 03:38:12,000 --> 03:38:13,560 FOR THE DIRECT TO PHASE TWO IF 6133 03:38:13,560 --> 03:38:15,400 YOU ALREADY HAVE FINISHED PROOF 6134 03:38:15,400 --> 03:38:16,600 OF CONCEPT STUDIES FOR YOUR 6135 03:38:16,600 --> 03:38:18,000 TECHNOLOGY, AND SOME INSTITUTES 6136 03:38:18,000 --> 03:38:20,560 OF NIH PROVIDE A FOLLOW-ON 6137 03:38:20,560 --> 03:38:22,840 FUNDING FOR PHASE TWO AWARDEES 6138 03:38:22,840 --> 03:38:25,040 CALLED PHASE 2B BRIDGE AWARD TO 6139 03:38:25,040 --> 03:38:27,760 BRIDGE THE GAP CALLED VALLEY OF 6140 03:38:27,760 --> 03:38:29,320 DEATH BETWEEN THE END OF FEDERAL 6141 03:38:29,320 --> 03:38:30,400 FUNDING AND THE BEGINNING OF 6142 03:38:30,400 --> 03:38:32,360 PRIVATE FUNDING. 6143 03:38:32,360 --> 03:38:34,120 WE GET A NUMBER OF QUESTIONS 6144 03:38:34,120 --> 03:38:41,760 REGARDING THE BUDGET GUIDELINES. 6145 03:38:41,760 --> 03:38:43,320 SOME OF THE OTHER INSTITUTES OF 6146 03:38:43,320 --> 03:38:45,720 NIH HAVE EVEN BIGGER -- HAVE 6147 03:38:45,720 --> 03:38:48,000 ABILITY TO FUND EVEN LARGER 6148 03:38:48,000 --> 03:38:51,520 PROJECTS FOR MANY TOPICS, AND A 6149 03:38:51,520 --> 03:38:53,160 LOT OF BUDGET FLEXIBILITIES 6150 03:38:53,160 --> 03:38:54,160 ACROSS NIH SO IT IS REALLY 6151 03:38:54,160 --> 03:38:55,600 IMPORTANT THAT YOU CONTACT THE 6152 03:38:55,600 --> 03:38:56,240 PROGRAM OFFICER BEFORE 6153 03:38:56,240 --> 03:38:58,520 SUBMITTING A PROPOSAL. 6154 03:38:58,520 --> 03:38:59,920 NOW LET'S TALK ABOUT DIFFERENT 6155 03:38:59,920 --> 03:39:02,680 FUNDING VEHICLES AT NIH. 6156 03:39:02,680 --> 03:39:05,520 GRANTS SUCH AS INVESTOR 6157 03:39:05,520 --> 03:39:06,960 INITIATED OMNIBUS SOLICITATIONS 6158 03:39:06,960 --> 03:39:08,080 OR TARGETED FUNDING 6159 03:39:08,080 --> 03:39:10,040 OPPORTUNITIES MAKE UP THE 6160 03:39:10,040 --> 03:39:13,200 BIGGEST CHUNK OF FUNDING. 6161 03:39:13,200 --> 03:39:16,160 THERE ARE THREE RECEIPT DATES 6162 03:39:16,160 --> 03:39:17,760 FOR THE GRANTS. 6163 03:39:17,760 --> 03:39:19,400 JANUARY 5TH, APRIL 5TH AND 6164 03:39:19,400 --> 03:39:22,200 SEPTEMBER 5TH OF EVERY YEAR. 6165 03:39:22,200 --> 03:39:24,280 SOME ICs SUCH AS NATIONAL 6166 03:39:24,280 --> 03:39:28,800 CANCER INSTITUTE IS -- AS A 6167 03:39:28,800 --> 03:39:30,760 MECHANISM TO FUND SCIENTIFIC AND 6168 03:39:30,760 --> 03:39:32,040 TECHNOLOGY PRIORITY AREAS OF 6169 03:39:32,040 --> 03:39:33,160 NCI. 6170 03:39:33,160 --> 03:39:35,120 KEEP IN MIND THESE ARE NOT THE 6171 03:39:35,120 --> 03:39:35,880 SERVICE CONTRACTS, THESE ARE 6172 03:39:35,880 --> 03:39:36,760 RESEARCH AND DEVELOPMENT 6173 03:39:36,760 --> 03:39:38,640 CONTRACTS. 6174 03:39:38,640 --> 03:39:41,200 EVERY YEAR NCI SOLICITS EIGHT TO 6175 03:39:41,200 --> 03:39:43,200 15 NEW CONTRACT AREAS AND I'M 6176 03:39:43,200 --> 03:39:45,320 GOING TO COME BACK TO ONE OF THE 6177 03:39:45,320 --> 03:39:47,560 CONTRACT TOPIC AREAS THAT WE 6178 03:39:47,560 --> 03:39:49,320 SOLICITED LAST YEAR THAT HAVE 6179 03:39:49,320 --> 03:39:53,080 STRONG POTENTIAL FOR COMMERCIAL 6180 03:39:53,080 --> 03:39:53,320 SUCCESS. 6181 03:39:53,320 --> 03:39:54,360 >> 2 MINUTES REMAINING. 6182 03:39:54,360 --> 03:39:55,480 >> HOW MANY? 6183 03:39:55,480 --> 03:39:57,360 >> 2 MINUTES. 6184 03:39:57,360 --> 03:39:58,560 >> SURE. 6185 03:39:58,560 --> 03:40:00,320 I'M JUST GOING TO -- SO THESE 6186 03:40:00,320 --> 03:40:03,440 ARE SOME OF THE FUNDING 6187 03:40:03,440 --> 03:40:03,760 OPPORTUNITIES. 6188 03:40:03,760 --> 03:40:04,840 IN THE INTEREST OF TIME, I'M 6189 03:40:04,840 --> 03:40:05,880 GOING TO GO A LITTLE FURTHER 6190 03:40:05,880 --> 03:40:06,440 AHEAD. 6191 03:40:06,440 --> 03:40:09,840 SO THE MAJOR DIFFERENCE BETWEEN 6192 03:40:09,840 --> 03:40:12,840 SBIR AND STTR GRANT AND ACADEMIC 6193 03:40:12,840 --> 03:40:17,360 GRANT IS A FOCUS OF SCIENCE. 6194 03:40:17,360 --> 03:40:19,560 IN CASE OF SBIR GRANTS, THEY'RE 6195 03:40:19,560 --> 03:40:22,600 FOCUSED ON CREATION OF PRODUCT 6196 03:40:22,600 --> 03:40:23,960 AS OPPOSED TO ACADEMIC GRANT, 6197 03:40:23,960 --> 03:40:26,440 WHICH IS BASED ON 6198 03:40:26,440 --> 03:40:28,640 HYPOTHESIS-DRIVEN SCIENCE. 6199 03:40:28,640 --> 03:40:29,520 THERE PRODUCT COULD BE A DRUG, 6200 03:40:29,520 --> 03:40:31,160 COULD BE A DIAGNOSTIC TEST, 6201 03:40:31,160 --> 03:40:33,440 COULD BE A RESEARCH TOOL OR 6202 03:40:33,440 --> 03:40:34,160 DEVICE OR EVEN A DIGITAL HEALTH 6203 03:40:34,160 --> 03:40:34,640 APP. 6204 03:40:34,640 --> 03:40:35,960 THE APPLICATIONS ARE JUST BASED 6205 03:40:35,960 --> 03:40:39,120 ON IF THE PROPOSED PRODUCT HAS A 6206 03:40:39,120 --> 03:40:41,520 COMPETITIVE ADVANTAGE OVER THE 6207 03:40:41,520 --> 03:40:43,720 OTHERS IN THE SAME AREA. 6208 03:40:43,720 --> 03:40:45,680 SO FOR EXAMPLE, DOES IT CHANGE 6209 03:40:45,680 --> 03:40:47,160 THE PARADIGM HOW THE DISEASE IS 6210 03:40:47,160 --> 03:40:53,360 TREATED OR DIAGNOSED, AND IF TH- 6211 03:40:53,360 --> 03:40:57,240 HAS ENOUGH EXPERIENCE. 6212 03:40:57,240 --> 03:40:58,720 GRANT APPLICANTS ALSO NEED TO 6213 03:40:58,720 --> 03:41:01,400 DESCRIBE HOW THEY WILL 6214 03:41:01,400 --> 03:41:02,400 COMMERCIALIZE ANY PRODUCT. 6215 03:41:02,400 --> 03:41:04,160 THESE ARE DIFFERENT WAYS HOW YOU 6216 03:41:04,160 --> 03:41:06,680 CAN COMMERCIALIZE YOUR TECH WITH 6217 03:41:06,680 --> 03:41:06,880 SBIR. 6218 03:41:06,880 --> 03:41:08,400 YOU CAN EITHER START YOUR OWN 6219 03:41:08,400 --> 03:41:09,840 COMPANY OR YOU CAN PARTNER WITH 6220 03:41:09,840 --> 03:41:12,240 AN EXISTING COMPANY OR AN 6221 03:41:12,240 --> 03:41:12,880 EXISTING SMALL BUSINESS TO 6222 03:41:12,880 --> 03:41:19,680 CONTINUE AS A P.I. 6223 03:41:19,680 --> 03:41:21,640 OR BY PARTNERING WITH AN 6224 03:41:21,640 --> 03:41:22,720 EXISTING SMALL BUSINESS. 6225 03:41:22,720 --> 03:41:24,600 EACH HAVE PROS AND CONS WHICH I 6226 03:41:24,600 --> 03:41:27,200 HAVE LISTED HERE. 6227 03:41:27,200 --> 03:41:29,160 SO WHY THE INTEREST IN LYMPHATIC 6228 03:41:29,160 --> 03:41:31,080 DISEASE, AND THE SHORT ANSWER IS 6229 03:41:31,080 --> 03:41:32,240 LYMPHEDEMA, ABOUT WHICH I REALLY 6230 03:41:32,240 --> 03:41:34,760 LEARNED A LOT IN TODAY'S MORNING 6231 03:41:34,760 --> 03:41:35,640 TALKS. 6232 03:41:35,640 --> 03:41:39,720 SO YOU KNOW, THIS AUDIENCE NEEDS 6233 03:41:39,720 --> 03:41:42,040 NO INTRODUCTION, THEY NOW HOW 6234 03:41:42,040 --> 03:41:43,240 DEBILL 6235 03:41:43,240 --> 03:41:48,240 DEBILITATING IT IS. 6236 03:41:48,240 --> 03:41:50,880 LAST YEAR WE PUBLISHED A 6237 03:41:50,880 --> 03:41:51,840 CONTRACT TOPIC TO DEVELOP NEW 6238 03:41:51,840 --> 03:41:53,600 TREATMENT MODALITIES FOR CANCER 6239 03:41:53,600 --> 03:41:55,040 PATIENTS SUFFERING FROM 6240 03:41:55,040 --> 03:41:56,560 LYMPHEDEMA. 6241 03:41:56,560 --> 03:41:59,600 THIS CONTRACT TOPIC IS NO LONGER 6242 03:41:59,600 --> 03:42:00,960 ACTIVE BUT MAY COME BACK IN THE 6243 03:42:00,960 --> 03:42:02,440 NEXT COUPLE OF YEARS. 6244 03:42:02,440 --> 03:42:05,080 IN ANY CASE, IF YOUR SMALL 6245 03:42:05,080 --> 03:42:07,800 BUSINESS HAS A TECHNOLOGY THAT 6246 03:42:07,800 --> 03:42:08,920 WILL BENEFIT THE EARLY DIAGNOSIS 6247 03:42:08,920 --> 03:42:11,080 OR TREATMENT OR PREVENTION OF 6248 03:42:11,080 --> 03:42:13,040 LYMPHEDEMA OR ANY OTHER 6249 03:42:13,040 --> 03:42:15,160 LYMPHATIC DISEASES FACED BY 6250 03:42:15,160 --> 03:42:17,360 CANCER PATIENTS, PLEASE CONTINUE 6251 03:42:17,360 --> 03:42:19,080 SUBMITTING AN SBIR/STTR GRANT 6252 03:42:19,080 --> 03:42:25,120 VIA THE OMNIBUS MECHANISM TO THE 6253 03:42:25,120 --> 03:42:25,560 NCI SBIR. 6254 03:42:25,560 --> 03:42:27,120 THESE ARE THE PROGRAM DIRECTORS 6255 03:42:27,120 --> 03:42:30,280 AND THEY DEAL ONLY WITH THE 6256 03:42:30,280 --> 03:42:30,880 SBIR/STTR GRANTS AND CONTRACTS 6257 03:42:30,880 --> 03:42:32,320 AND NOT WITH ANY ACADEMIC GRANTS 6258 03:42:32,320 --> 03:42:33,640 SUCH AS R01. 6259 03:42:33,640 --> 03:42:36,840 SO IF YOU'RE PLANNING TO SPLIT 6260 03:42:36,840 --> 03:42:38,240 SBIR/STTR GRANTS, SEND YOUR 6261 03:42:38,240 --> 03:42:39,680 SPECIFIC AIMS PAGE, WE HAVE THE 6262 03:42:39,680 --> 03:42:44,040 EMAIL GIVEN HERE. 6263 03:42:44,040 --> 03:42:46,560 THIS IS OUR CONTACT INFORMATION, 6264 03:42:46,560 --> 03:42:47,760 AND DIFFERENT SOCIAL MEDIA 6265 03:42:47,760 --> 03:42:48,840 INFORMATION. 6266 03:42:48,840 --> 03:42:55,200 AND I WILL STOP HERE AND STOP 6267 03:42:55,200 --> 03:42:57,280 SHARING MY SLIDES. 6268 03:42:57,280 --> 03:42:58,560 >> THANK YOU, REEMA. 6269 03:42:58,560 --> 03:43:04,400 ARE THERE ANY QUESTIONS FOR 6270 03:43:04,400 --> 03:43:05,400 DR. RAILKAR? 6271 03:43:05,400 --> 03:43:06,560 SELEN, YOU HAVE A QUESTION? 6272 03:43:06,560 --> 03:43:07,720 >> YES. 6273 03:43:07,720 --> 03:43:10,360 REEMA, I WAS GOING TO ASK ONE OF 6274 03:43:10,360 --> 03:43:12,840 THE MOST COMMON QUESTIONS THAT I 6275 03:43:12,840 --> 03:43:16,480 GET FROM OUR APPLICANTS IS THAT 6276 03:43:16,480 --> 03:43:17,480 THEY ARE MORE FAMILIAR WITH THE 6277 03:43:17,480 --> 03:43:19,120 RESEARCH GRANT AND WHAT'S THE 6278 03:43:19,120 --> 03:43:22,920 ROAD MAP OF A SUCCESSFUL 6279 03:43:22,920 --> 03:43:24,840 SBIR/STTR GRANT, IF THEY NEED A 6280 03:43:24,840 --> 03:43:25,840 BUSINESS PLAN? 6281 03:43:25,840 --> 03:43:27,680 >> SO FOR PHASE ONE, YOU DO NOT 6282 03:43:27,680 --> 03:43:29,200 NEED A BUSINESS PLAN. 6283 03:43:29,200 --> 03:43:32,600 AND IF YOU HAVE NEVER APPLIED 6284 03:43:32,600 --> 03:43:38,840 FOR A SBIR/STTR GRANT BEFORE, A 6285 03:43:38,840 --> 03:43:40,800 NUMBER OF DIFFERENT INSTITUTES 6286 03:43:40,800 --> 03:43:44,200 AT NIH INCLUDING NCI, NHLBI, AND 6287 03:43:44,200 --> 03:43:46,800 OTHERS, HAVE A PROGRAM CALLED 6288 03:43:46,800 --> 03:43:47,960 APPLICANT ASSISTANCE PROGRAM. 6289 03:43:47,960 --> 03:43:49,240 THIS IS NOT A GRANT-WRITER, BUT 6290 03:43:49,240 --> 03:43:52,360 THEY ACTUALLY HELP YOU, IF YOU 6291 03:43:52,360 --> 03:43:53,760 GET SELECTED, IT'S A COMPETITIVE 6292 03:43:53,760 --> 03:43:55,400 PROGRAM FREE OF COST TO THE 6293 03:43:55,400 --> 03:43:56,920 APPLICANT, AND IF YOU GET 6294 03:43:56,920 --> 03:43:59,560 SELECTED, THE NIH CONTRACTOR 6295 03:43:59,560 --> 03:44:00,000 HELPS YOU. 6296 03:44:00,000 --> 03:44:06,560 IT'S A 10-WEEK PROGRAM, TO WRITE 6297 03:44:06,560 --> 03:44:08,120 YOUR GRANT, SO FOR EXAMPLE, THE 6298 03:44:08,120 --> 03:44:09,840 WEEK ONE IS BASICALLY, YOU KNOW, 6299 03:44:09,840 --> 03:44:11,040 YOU HAVE TO COME UP WITH YOUR 6300 03:44:11,040 --> 03:44:14,360 OWN RESEARCH STRATEGY. 6301 03:44:14,360 --> 03:44:16,600 BUT THEY WILL GUIDE YOU HOW TO 6302 03:44:16,600 --> 03:44:19,040 DEVELOP THE BUDGET, HOW TO 6303 03:44:19,040 --> 03:44:22,000 DEVELOP THE WHOLE, YOU KNOW, 6304 03:44:22,000 --> 03:44:23,320 SPECIFIC AIMS PAGE AND ALL THOSE 6305 03:44:23,320 --> 03:44:25,720 DIFFERENT THINGS. 6306 03:44:25,720 --> 03:44:28,560 SO ONE OF THE WAYS IS FIRST OF 6307 03:44:28,560 --> 03:44:30,120 ALL COMMIT TO THE PROGRAM 6308 03:44:30,120 --> 03:44:30,520 DIRECTORS. 6309 03:44:30,520 --> 03:44:31,840 WE HAVE A LOT OF OUTREACH EVENTS 6310 03:44:31,840 --> 03:44:32,920 AND THIS WAS JUST 10 MINUTES BUT 6311 03:44:32,920 --> 03:44:34,480 WE DO A LOT OF DIFFERENT 6312 03:44:34,480 --> 03:44:36,680 OUTREACH EVENTS THAT GO UP TO AN 6313 03:44:36,680 --> 03:44:38,000 HOUR, HOUR AND A HALF WHERE WE 6314 03:44:38,000 --> 03:44:39,640 ACTUALLY GO IN DETAILS HOW TO 6315 03:44:39,640 --> 03:44:43,120 WRITE THESE GRANTS. 6316 03:44:43,120 --> 03:44:44,680 SO THOSE ARE A COUPLE OF WAYS 6317 03:44:44,680 --> 03:44:47,560 YOU CAN WRITE THE SBIR/STTR 6318 03:44:47,560 --> 03:44:47,760 GRANTS. 6319 03:44:47,760 --> 03:44:51,120 >> THANK YOU. 6320 03:44:51,120 --> 03:44:53,000 >> THANK YOU, REEMA. 6321 03:44:53,000 --> 03:44:58,000 ARE THERE ANY OTHER QUESTIONS? 6322 03:44:58,000 --> 03:45:00,240 WELL, SO I GUESS IT NOW TIME TO 6323 03:45:00,240 --> 03:45:02,720 TAKE A BREAK FOR LUNCH. 6324 03:45:02,720 --> 03:45:05,240 AND WE WILL BE BACK TO START 6325 03:45:05,240 --> 03:45:08,440 SESSION NUMBER SEVEN AT 6326 03:45:08,440 --> 03:45:09,720 1:30 P.M. EASTERN TIME. 6327 03:45:09,720 --> 03:45:11,200 THANK YOU ALL. 6328 03:45:11,200 --> 03:45:13,080 THANK YOU ALL FOR A WONDERFUL 6329 03:45:13,080 --> 03:45:19,960 MORNING. 6330 03:45:19,960 --> 03:45:21,200 >>IT'S 1:30. 6331 03:45:21,200 --> 03:45:23,680 LET'S GET STARTED WITH THE LAST 6332 03:45:23,680 --> 03:45:24,000 SESSION. 6333 03:45:24,000 --> 03:45:25,280 >> OK, GREAT. 6334 03:45:25,280 --> 03:45:26,280 IT'S MY PLEASURE NOW TO 6335 03:45:26,280 --> 03:45:29,360 INTRODUCE OUR CO-CHAIR, Dr. 6336 03:45:29,360 --> 03:45:29,680 ANDREA RADTKE. 6337 03:45:29,680 --> 03:45:30,880 SHE'S A ASSOCIATE SCIENTIST 6338 03:45:30,880 --> 03:45:32,680 WITHIN THE INTRAMURAL PROGRAM AT 6339 03:45:32,680 --> 03:45:34,680 THE NIH INSTITUTE OF ALLERGY AND 6340 03:45:34,680 --> 03:45:38,400 INFECTIOUS DISEASES AND SHE 6341 03:45:38,400 --> 03:45:39,560 SPECIALIZES IN VAST FACIAL 6342 03:45:39,560 --> 03:45:41,440 MAPPING OF DIVERSE TISSUE. 6343 03:45:41,440 --> 03:45:45,200 PLEASE JOIN ME IN WELCOMING HER. 6344 03:45:45,200 --> 03:45:47,160 >> THANK YOU, BABAK. 6345 03:45:47,160 --> 03:45:48,960 YEAH, IT'S MY PLEASURE TO 6346 03:45:48,960 --> 03:45:50,760 MODERATE THIS SPECIAL SESSION, 6347 03:45:50,760 --> 03:45:53,000 OUR LAST SESSION OF THE TWO-DAY 6348 03:45:53,000 --> 03:45:54,400 SYMPOSIUM FEATURING NEW 6349 03:45:54,400 --> 03:45:55,440 TECHNOLOGIES IN LYMPHATIC 6350 03:45:55,440 --> 03:45:56,320 IMAGING AND MAPPING. 6351 03:45:56,320 --> 03:45:57,960 THE TECHNOLOGIES DISCUSSED HERE 6352 03:45:57,960 --> 03:45:59,520 PROVIDE EYE MEANS TO EVALUATE 6353 03:45:59,520 --> 03:46:01,640 THE LYMPHATIC SYSTEM ACROSS 6354 03:46:01,640 --> 03:46:04,480 SCALES FROM SINGLE-CELL TO MACRO 6355 03:46:04,480 --> 03:46:05,680 ANATOMICAL STRUCTURES TO DATA 6356 03:46:05,680 --> 03:46:06,880 FROM CLINICAL COHORTS. 6357 03:46:06,880 --> 03:46:08,440 IT'S OUR HOPE THE NEW 6358 03:46:08,440 --> 03:46:09,320 TECHNOLOGIES OUTLINED HERE 6359 03:46:09,320 --> 03:46:10,800 ADVANCE OUR UNDERSTANDING OF THE 6360 03:46:10,800 --> 03:46:12,320 HUMAN LYMPHATIC SYSTEM WHILE 6361 03:46:12,320 --> 03:46:13,840 PROVIDING A MEANS TO IMPROVE THE 6362 03:46:13,840 --> 03:46:14,800 TREATMENT AND PREVENTION OF 6363 03:46:14,800 --> 03:46:15,960 LYMPHATIC DISEASES. 6364 03:46:15,960 --> 03:46:18,160 OUR FIRST SPEAKER THIS SESSION 6365 03:46:18,160 --> 03:46:19,080 IS MAX. 6366 03:46:19,080 --> 03:46:21,280 Dr. MAX ITSKIN, THE DIRECTOR 6367 03:46:21,280 --> 03:46:23,560 OF THE PENN CENTER FOR DISORDERS 6368 03:46:23,560 --> 03:46:26,280 AND PROFESSOR OF RADIOLOGY AT 6369 03:46:26,280 --> 03:46:28,080 THE UNIVERSITY OF PENNSYLVANIA. 6370 03:46:28,080 --> 03:46:29,400 HE WILL PRESENT IMAGING 6371 03:46:29,400 --> 03:46:30,320 APPROACHES AND THEIR 6372 03:46:30,320 --> 03:46:31,440 APPLICATIONS IN THE CLINICKING. 6373 03:46:31,440 --> 03:46:33,840 THE TITLE OF HIS TALK IS 6374 03:46:33,840 --> 03:46:35,240 "LYMPHATIC ANATOMICAL VARIANTS 6375 03:46:35,240 --> 03:46:37,160 AS A DISEASE MECHANISM, THE 6376 03:46:37,160 --> 03:46:39,160 IMPORTANCE OF ANATOMICAL 6377 03:46:39,160 --> 03:46:39,400 MAPPING. 6378 03:46:39,400 --> 03:46:41,520 THANK YOU MAX AND THANK YOU ALL. 6379 03:46:41,520 --> 03:46:46,320 >> THANK YOU, A LOT, ANDREA. 6380 03:46:46,320 --> 03:46:49,160 YOU CAN SEE MY SLIDES HERE. 6381 03:46:49,160 --> 03:46:50,320 >> YES, LOOKS GREAT. 6382 03:46:50,320 --> 03:46:51,360 >> THANK YOU, A LOT. 6383 03:46:51,360 --> 03:46:54,080 IT'S A GREAT HONOR TO BE HERE 6384 03:46:54,080 --> 03:46:55,240 AND SECOND YEAR I PARTICIPATED 6385 03:46:55,240 --> 03:46:58,000 IN NIH WORKSHOP AND IT'S REALLY 6386 03:46:58,000 --> 03:47:00,120 AMAZING TO HAVE DONE ALL THESE 6387 03:47:00,120 --> 03:47:00,600 THINGS. 6388 03:47:00,600 --> 03:47:05,480 SO WE TALK, I TALK ABOUT CENTER 6389 03:47:05,480 --> 03:47:05,800 OF. 6390 03:47:05,800 --> 03:47:09,760 IT MEANS EVERYTHING BUT 6391 03:47:09,760 --> 03:47:11,720 EXTREMITIES. 6392 03:47:11,720 --> 03:47:15,320 THE CENTRAL LYMPHATICS HAVE BEEN 6393 03:47:15,320 --> 03:47:17,120 A KNOWN FOR MANY YEARS BECAUSE 6394 03:47:17,120 --> 03:47:21,120 IT'S VERY, VERY HARD TO SEE 6395 03:47:21,120 --> 03:47:21,440 THEM. 6396 03:47:21,440 --> 03:47:25,360 IT'S HARD TO UNDERSTAND THEIR 6397 03:47:25,360 --> 03:47:26,560 PATHOLOGY OF THE CENTRAL 6398 03:47:26,560 --> 03:47:27,600 LYMPHATIC SYSTEM BECAUSE WE 6399 03:47:27,600 --> 03:47:30,120 DIDN'T HAVE A GOOD IMAGING. 6400 03:47:30,120 --> 03:47:32,440 OF COURSE, WHEN YOU TALK ABOUT 6401 03:47:32,440 --> 03:47:33,680 IT'S AVAILABLE TO SEE THE PEOPLE 6402 03:47:33,680 --> 03:47:35,000 AND YOU CAN ADDRESS IT BUT 6403 03:47:35,000 --> 03:47:37,760 CENTRAL NOT THAT MUCH. 6404 03:47:37,760 --> 03:47:43,320 CENTRAL LYMPHATIC ANATOMY 6405 03:47:43,320 --> 03:47:45,480 EXTREMELY COMPLEX. 6406 03:47:45,480 --> 03:47:48,160 THERE'S ALSO EXTREME VARIABILITY 6407 03:47:48,160 --> 03:47:49,600 IN THIS SYSTEM. 6408 03:47:49,600 --> 03:47:52,320 AND IT'S REALLY DIFFICULT TO 6409 03:47:52,320 --> 03:47:54,600 INVESTIGATE IN CLINICAL SETTINGS 6410 03:47:54,600 --> 03:47:56,960 BECAUSE THE SIZE IS SMALL AND 6411 03:47:56,960 --> 03:47:59,760 IT'S HARD TO INTRODUCE CONTRAST. 6412 03:47:59,760 --> 03:48:01,480 SO THIS IS JUST TO SHOW THE 6413 03:48:01,480 --> 03:48:05,040 DIFFERENCE IN COMPLEXITY OF THE 6414 03:48:05,040 --> 03:48:06,840 LYMPHATIC SYSTEM AND THE 6415 03:48:06,840 --> 03:48:09,240 VASCULAR SYSTEM AND IT'S ALL 6416 03:48:09,240 --> 03:48:10,120 DRUGS OF COURSE. 6417 03:48:10,120 --> 03:48:14,040 THIS VARIATION OF THE LYMPHATIC 6418 03:48:14,040 --> 03:48:15,640 HAS BEEN KNOWN FOR MANY YEARS 6419 03:48:15,640 --> 03:48:17,880 AND THIS IS A PAPER FROM 1915 BY 6420 03:48:17,880 --> 03:48:21,520 Dr. DAVIS, WHO DID THIS 6421 03:48:21,520 --> 03:48:24,160 STATISTICAL STUDY OF THE MAN ON 6422 03:48:24,160 --> 03:48:27,640 120 AND HE DISCOVERED NINE TYPES 6423 03:48:27,640 --> 03:48:31,160 OF THORACIC TO MOST COLON TYPE 6424 03:48:31,160 --> 03:48:36,400 TWO AND SIX THE ONLY 40% OF THE 6425 03:48:36,400 --> 03:48:36,680 STUDY. 6426 03:48:36,680 --> 03:48:39,560 SO, WHY IS THIS SO COMPLEX? 6427 03:48:39,560 --> 03:48:42,720 BECAUSE IT'S DEVELOPED COMPLEX. 6428 03:48:42,720 --> 03:48:46,040 IT DEVELOPED FROM DIFFERENT 6429 03:48:46,040 --> 03:48:47,880 VEINS AND THEN THEY FUSED 6430 03:48:47,880 --> 03:48:49,680 TOGETHER AND THERE ARE MISTAKES 6431 03:48:49,680 --> 03:48:54,840 IN THIS FUSION CAN CAUSE THIS 6432 03:48:54,840 --> 03:48:57,040 VARIATION OF NORMALITY FOR 6433 03:48:57,040 --> 03:48:58,040 LYMPHATIC SYSTEM. 6434 03:48:58,040 --> 03:49:00,920 UNTIL RECENTLY, THE LYMPHATIC 6435 03:49:00,920 --> 03:49:07,160 SEARCH WAS BASED PRIMARILY ON 6436 03:49:07,160 --> 03:49:09,360 DIE SEX AND AND BECAUSE OF THE 6437 03:49:09,360 --> 03:49:10,520 SIZE OF OF LYMPHATIC CELLS IT'S 6438 03:49:10,520 --> 03:49:14,360 VERY HARD TO IDENTIFY THEM, 6439 03:49:14,360 --> 03:49:15,640 ALSO, THE CASTING TECHNIQUES 6440 03:49:15,640 --> 03:49:20,280 THAT USED FOR ANY VASCULAR HAVE 6441 03:49:20,280 --> 03:49:21,240 LIMITATIONS FROM LYMPHATIC 6442 03:49:21,240 --> 03:49:22,920 SYSTEM BECAUSE PRESENCE OF THE 6443 03:49:22,920 --> 03:49:26,120 VALUES THAT SOMETIMES PREVENT 6444 03:49:26,120 --> 03:49:27,080 PROPAGATION OF THE RAISE INTO 6445 03:49:27,080 --> 03:49:30,600 THE DIFFERENT AREAS OF LYMPHATIC 6446 03:49:30,600 --> 03:49:31,080 SYSTEM. 6447 03:49:31,080 --> 03:49:34,160 AND THERE'S NO UNDERSTANDING OF 6448 03:49:34,160 --> 03:49:34,960 REAL-TIME FLOW DIRECTION IN THE 6449 03:49:34,960 --> 03:49:36,360 LYMPHATIC SYSTEM AND 6450 03:49:36,360 --> 03:49:37,160 COMMUNICATION BETWEEN DIFFERENT 6451 03:49:37,160 --> 03:49:38,840 TYPES OF LYMPHATIC SYSTEM 6452 03:49:38,840 --> 03:49:41,120 BECAUSE EACH ORGAN IN THE BODY 6453 03:49:41,120 --> 03:49:43,560 HAS ITS OWN LYMPHATIC SYSTEM 6454 03:49:43,560 --> 03:49:45,000 THAT FUNCTIONS DIFFERENT AND 6455 03:49:45,000 --> 03:49:48,600 CREATES THE LYMPH IN A DIFFERENT 6456 03:49:48,600 --> 03:49:48,800 WAY. 6457 03:49:48,800 --> 03:49:57,480 THOSE ARE VERY, VERY IMPORTANT. 6458 03:49:57,480 --> 03:49:58,680 IT STARTED SEVEN OR EIGHT YEARS 6459 03:49:58,680 --> 03:50:00,720 AGO AND THIS IS A LIST OF 6460 03:50:00,720 --> 03:50:02,600 DIFFERENT TECHNIQUES THAT 6461 03:50:02,600 --> 03:50:07,160 STARTED WITH GEOGRAPHY AND MRI 6462 03:50:07,160 --> 03:50:11,520 AND AND CT AND MORE. 6463 03:50:11,520 --> 03:50:14,560 THIS IS A FIRST STEP. 6464 03:50:14,560 --> 03:50:22,800 THE FIRST INTRAANODAL 6465 03:50:22,800 --> 03:50:23,200 LYMPHANGIOGRAPHY. 6466 03:50:23,200 --> 03:50:25,360 YOU TAKE THE NEEDLE AND APPROACH 6467 03:50:25,360 --> 03:50:28,200 IT IN THE MASS AND INJECT 6468 03:50:28,200 --> 03:50:28,440 CONTRAST. 6469 03:50:28,440 --> 03:50:32,400 THIS IS IMAGES ON THE LEFT, THIS 6470 03:50:32,400 --> 03:50:33,800 IS SCOPE I CAN AND THAT'S HOW IT 6471 03:50:33,800 --> 03:50:35,760 LOOKS ON THE PATIENT. 6472 03:50:35,760 --> 03:50:38,320 YOU CAN APPLY THIS TECHNIQUE 6473 03:50:38,320 --> 03:50:41,080 EVERYWHERE WHERE THERE ARE REACH 6474 03:50:41,080 --> 03:50:47,880 LYMPHATIC TISSUE, AGAIN, GROWING 6475 03:50:47,880 --> 03:50:52,000 AND LYMPH NODES AND AND 6476 03:50:52,000 --> 03:50:53,520 SURPRISING BECAUSE LEVER PORTAL 6477 03:50:53,520 --> 03:50:54,920 LYMPHATIC SYSTEM ARE BIG AND YOU 6478 03:50:54,920 --> 03:50:58,120 CAN ACTUALLY SEE THEM AND ACCESS 6479 03:50:58,120 --> 03:51:02,120 THEM AND THIS IS TWO EXAMPLES OF 6480 03:51:02,120 --> 03:51:06,240 THE LEFT MR ON THE RIGHT ON THE 6481 03:51:06,240 --> 03:51:08,880 LEFT WE HAVE INJECT AND ON THE 6482 03:51:08,880 --> 03:51:11,480 RIGHT CONTRAST AND IT WAS 6483 03:51:11,480 --> 03:51:14,040 DEVELOPED FIRST AND RECENTLY WE 6484 03:51:14,040 --> 03:51:16,680 STARTED TO DO MORE AND MORE CT 6485 03:51:16,680 --> 03:51:18,360 AND IT'S MUCH EASIER FOR PEOPLE 6486 03:51:18,360 --> 03:51:20,560 TO DO. 6487 03:51:20,560 --> 03:51:22,160 LIVER, YOU PUT THE NEEDLE CLOSE 6488 03:51:22,160 --> 03:51:26,400 TO THE PORTAL VEIN AND IF THE 6489 03:51:26,400 --> 03:51:30,080 LIVER IS CO CONGESTED YOU CAN SE 6490 03:51:30,080 --> 03:51:31,720 THE LYMPHATIC QUITE WELL AND ADD 6491 03:51:31,720 --> 03:51:33,960 CROSS SECTION IMAGING TO THAT, 6492 03:51:33,960 --> 03:51:37,960 C.T., ROTATIONAL TC SOMETIMES 6493 03:51:37,960 --> 03:51:39,480 GET INFORMATION AND WE DON'T 6494 03:51:39,480 --> 03:51:42,240 FIND IT EXTRAORDINARILY USEFUL. 6495 03:51:42,240 --> 03:51:45,320 WHAT DID WE DISCOVER OVER IS 6496 03:51:45,320 --> 03:51:48,840 THIS SEVEN OR EIGHT YEARS. 6497 03:51:48,840 --> 03:51:51,080 IT'S ALL INVOLVED NORMAL 6498 03:51:51,080 --> 03:51:52,200 LYMPHATIC ANATOMY. 6499 03:51:52,200 --> 03:51:55,200 THERE ARE TWO TYPES, SOMETHING 6500 03:51:55,200 --> 03:51:56,480 DEVELOPED OBSTRUCTION AND 6501 03:51:56,480 --> 03:51:57,280 OBSTRUCTION OF THE LYMPHATIC 6502 03:51:57,280 --> 03:52:00,080 SYSTEM AND DEVELOPMENT OF 6503 03:52:00,080 --> 03:52:06,000 PATHWAYS AND USUALLY IT WAS THIS 6504 03:52:06,000 --> 03:52:16,520 WITH LYMPHATIC AND IT'S WORKS 6505 03:52:19,040 --> 03:52:19,880 QUITE WELL. 6506 03:52:19,880 --> 03:52:23,760 SO, THIS IS A DIFFERENT TYPE OF 6507 03:52:23,760 --> 03:52:24,960 LYMPHATIC VARIANTS. 6508 03:52:24,960 --> 03:52:27,800 WE START WITH THORACIC DUCT. 6509 03:52:27,800 --> 03:52:30,800 IT'S BEEN IN FOCUS OF LYMPHATIC 6510 03:52:30,800 --> 03:52:32,840 RESEARCH FOR MANY, MANY YEARS, 6511 03:52:32,840 --> 03:52:35,040 OVER 100 YEARS AND PEOPLE MANY 6512 03:52:35,040 --> 03:52:43,320 YEARS AGO FIGURE OUT THAT IT CAN 6513 03:52:43,320 --> 03:52:44,600 CAUSE DIFFERENT PROBLEMS, THIS 6514 03:52:44,600 --> 03:52:45,800 IS A INCOMPLETE LIST OF THE 6515 03:52:45,800 --> 03:52:51,320 CONDITIONS WE TREAT RIGHT NOW. 6516 03:52:51,320 --> 03:52:55,320 LOW AB NOM INEXTREMITY AND MORE 6517 03:52:55,320 --> 03:52:56,400 AND MORE. 6518 03:52:56,400 --> 03:53:02,440 THE SECOND ONE THAT ACTUALLY WAS 6519 03:53:02,440 --> 03:53:04,640 CHRONOLOGICALLY TO FIGURE OUT IS 6520 03:53:04,640 --> 03:53:10,600 IT CAN CAUSE BRONCHITIS AND THE 6521 03:53:10,600 --> 03:53:16,840 LAST ONE HERE IS LYMPHATICS AND 6522 03:53:16,840 --> 03:53:21,400 THE LIVER/RETROPERITON AND MORE 6523 03:53:21,400 --> 03:53:23,800 SO THIS IS EXAMPLE OF THE 6524 03:53:23,800 --> 03:53:26,360 ABNORMAL PULMONARY LYMPHATIC 6525 03:53:26,360 --> 03:53:27,920 FLOW ON THE LEFT AND ON THE 6526 03:53:27,920 --> 03:53:31,400 RIGHT YOU CAN SEE NORMAL AND ON 6527 03:53:31,400 --> 03:53:34,720 THE FAR-RIGHT YOU CAN SEE THIS 6528 03:53:34,720 --> 03:53:38,440 ABNORMAL FROM THORACIC INTO LUNG 6529 03:53:38,440 --> 03:53:42,200 WITH PLASTIC BRONCHITIS AND THE 6530 03:53:42,200 --> 03:53:44,920 SAME IDEA HERE, THIS IS 6531 03:53:44,920 --> 03:53:46,440 NEONATAL, THE SAME EXACT 6532 03:53:46,440 --> 03:53:47,760 PROCESS. 6533 03:53:47,760 --> 03:53:49,760 OBSTRUCTION OF THE PART OF THE 6534 03:53:49,760 --> 03:53:52,360 THORACIC OF FLUID IN THE LUNG 6535 03:53:52,360 --> 03:53:56,000 AND OF COURSE, THIS IS GEOGRAPHY 6536 03:53:56,000 --> 03:53:57,920 AND LUNG DISEASE AND CAN BE 6537 03:53:57,920 --> 03:54:04,920 CAUSED BY THIS SAME PROCESS. 6538 03:54:04,920 --> 03:54:06,320 LIVER, WE PERFORM MORE AND MORE 6539 03:54:06,320 --> 03:54:07,160 OF THOSE. 6540 03:54:07,160 --> 03:54:08,640 USUALLY WHEN WE PUT THE NEEDLE 6541 03:54:08,640 --> 03:54:10,280 IN THE LIVER AND INJECT IN 6542 03:54:10,280 --> 03:54:12,760 NORMAL SITUATIONS, YOU CAN SEE 6543 03:54:12,760 --> 03:54:17,400 THAT THERE ARE COMMUNICATIONS 6544 03:54:17,400 --> 03:54:19,200 THORACIC WITH THE DUCT. 6545 03:54:19,200 --> 03:54:21,200 IT'S ACTUALLY BECAUSE PRIMARILY 6546 03:54:21,200 --> 03:54:23,040 WE SEE ABNORMAL SO IT'S ONE OR 6547 03:54:23,040 --> 03:54:27,320 TWO NORMAL CASES I HAVE. 6548 03:54:27,320 --> 03:54:29,360 BUT, I'LL SHOW YOU SOME ABNORMAL 6549 03:54:29,360 --> 03:54:31,240 BUT WHAT IS IMPORTANT TO 6550 03:54:31,240 --> 03:54:33,000 UNDERSTAND IS THIS PART OF THE 6551 03:54:33,000 --> 03:54:34,600 UPPER ABDOMEN. 6552 03:54:34,600 --> 03:54:36,560 THE LYMPHATIC PART OF THE UPPER 6553 03:54:36,560 --> 03:54:36,880 ABDOMEN. 6554 03:54:36,880 --> 03:54:38,480 IT'S ACTUALLY THE CROSS ROADS 6555 03:54:38,480 --> 03:54:40,280 THE MOST BUSIEST PART OF THE 6556 03:54:40,280 --> 03:54:43,320 LYMPHATIC SYSTEM WHERE ALL 6557 03:54:43,320 --> 03:54:48,360 LYMPHATIC VESSELS MEET. 6558 03:54:48,360 --> 03:54:53,440 FROM LIVER, PANCREAS, SPLEEN, 6559 03:54:53,440 --> 03:54:54,600 KIDNEYS, EVERYTHING COMES THERE 6560 03:54:54,600 --> 03:54:58,280 SO THIS STUDY Dr. DEKI FROM 6561 03:54:58,280 --> 03:55:01,920 JAPAN DID THIS DIE SECKION AND 6562 03:55:01,920 --> 03:55:03,280 DEMONSTRATED HOW COMPLEX IT IS. 6563 03:55:03,280 --> 03:55:05,080 YOU CAN IMAGINE, IF YOU HAVE A 6564 03:55:05,080 --> 03:55:06,880 LYMPHATIC SYSTEM UNDER CERTAIN 6565 03:55:06,880 --> 03:55:09,960 STRESS LIKE HEART FAILURE, IF 6566 03:55:09,960 --> 03:55:11,040 THIS LYMPHATIC VESSEL COMES 6567 03:55:11,040 --> 03:55:17,200 CLOSE TO THE SURFACE OF THE THEY 6568 03:55:17,200 --> 03:55:18,200 CAN LEAK AND CAUSE PROTEIN. 6569 03:55:18,200 --> 03:55:21,840 IN OTHER CASES, THIS IS A SIGN 6570 03:55:21,840 --> 03:55:23,640 OF HEART FAILURE WHERE THIS 6571 03:55:23,640 --> 03:55:26,240 ABNORMAL FLOW OF THE LYMPH FROM 6572 03:55:26,240 --> 03:55:31,680 THE CONGESTED LIVER INTO THAT 6573 03:55:31,680 --> 03:55:32,080 CAUSE. 6574 03:55:32,080 --> 03:55:36,480 THE NEXT ONE IS PROBABLY THE 6575 03:55:36,480 --> 03:55:41,160 FOCUSED ON A LOT RIGHT NOW ON 6576 03:55:41,160 --> 03:55:41,400 THIS. 6577 03:55:41,400 --> 03:55:43,040 WE DISCARD MULTIPLE DISEASES 6578 03:55:43,040 --> 03:55:46,560 THAT THESE OBSTRUCTIONS. 6579 03:55:46,560 --> 03:55:49,320 AND AGAIN, IT'S HIGHLY VARIABLE 6580 03:55:49,320 --> 03:55:52,080 AND IN A FOCUS OF THE LYMPHATIC 6581 03:55:52,080 --> 03:55:54,240 RESEARCH FOR AGAIN, AT LEAST 100 6582 03:55:54,240 --> 03:55:56,720 YEARS, AND YOU CAN SEE THIS IS A 6583 03:55:56,720 --> 03:56:02,640 PAPER FROM 1977 WHERE CADAVER 6584 03:56:02,640 --> 03:56:05,360 STUDY SHOWS THE DIFFERENT 6585 03:56:05,360 --> 03:56:06,760 VARIANTS OF THE COMMUNICATION 6586 03:56:06,760 --> 03:56:10,720 WITH THORACIC AND VENUS SYSTEM 6587 03:56:10,720 --> 03:56:13,840 AND OF COURSE, THIS 6588 03:56:13,840 --> 03:56:14,760 COMMUNICATION, OF NO 6589 03:56:14,760 --> 03:56:16,680 COMMUNICATION CAN CAUSE VARIETY 6590 03:56:16,680 --> 03:56:18,000 OF THE PROBLEMS UPSTREAM. 6591 03:56:18,000 --> 03:56:22,920 THIS IS NOT A STUDY FROM NEW 6592 03:56:22,920 --> 03:56:28,600 ZEALAND, RECENTLY FROM 2020. 6593 03:56:28,600 --> 03:56:30,960 THIS IS HOW NORMAL THORACIC DUCT 6594 03:56:30,960 --> 03:56:32,120 LOOKS LIKE. 6595 03:56:32,120 --> 03:56:34,320 SINGLE AND DOZE INTO THE VEIN. 6596 03:56:34,320 --> 03:56:38,680 THIS IS A CHILD WITH HIGH TROPES 6597 03:56:38,680 --> 03:56:41,560 AND IT'S NOT ABSENT AND IT'S 6598 03:56:41,560 --> 03:56:45,320 PRACTICALLY ABSENT. 6599 03:56:45,320 --> 03:56:49,160 THIS IS ANOTHER CONDITION. 6600 03:56:49,160 --> 03:56:52,800 YOU CAN SEE THAT INSTEAD OF NICE 6601 03:56:52,800 --> 03:56:56,600 AND CURVE EMPTY INSIDE THE VEIN 6602 03:56:56,600 --> 03:57:00,200 IS ACTUAL LOW VERY, VERY 6603 03:57:00,200 --> 03:57:02,720 TORTUROUS AND IT CREATES THE 6604 03:57:02,720 --> 03:57:04,520 OBSTRUCTION OF THORACIC DUCT 6605 03:57:04,520 --> 03:57:07,240 RESULTING IN THE DEPOSITION OF 6606 03:57:07,240 --> 03:57:11,360 DEBRIS AND AND OPENING THIS 6607 03:57:11,360 --> 03:57:13,680 OBSTRUCTION RELIEF PAIN. 6608 03:57:13,680 --> 03:57:17,720 THE ANGLE HOW THORACIC GETS INTO 6609 03:57:17,720 --> 03:57:21,920 THE VEIN CAUSED THE PATIENT POST 6610 03:57:21,920 --> 03:57:25,600 RIVER TRANSPLANT AND THIS IS 6611 03:57:25,600 --> 03:57:26,920 LIVER TRANSPLANT AGAIN YOU CAN 6612 03:57:26,920 --> 03:57:28,960 SEE THAT INSTEAD OF ONE THORACIC 6613 03:57:28,960 --> 03:57:39,400 DUCT THERE ARE MULTIPLE BRANCHES 6614 03:57:39,400 --> 03:57:40,480 AND THIS RESULT AND RESOLUTION 6615 03:57:40,480 --> 03:57:41,840 OF THE SYSTEMS. 6616 03:57:41,840 --> 03:57:46,480 SO A MAT K ANATOMY IS THE ANSWE. 6617 03:57:46,480 --> 03:57:47,280 THERE'S LYMPHATIC FLOW AS WELL 6618 03:57:47,280 --> 03:57:49,120 BUT I'M NOT TALKING ABOUT THAT. 6619 03:57:49,120 --> 03:57:53,720 BECAUSE WHAT WE ALSO FOUND IS 6620 03:57:53,720 --> 03:57:56,080 THAT THE AMOUNT OF LYMPHATIC 6621 03:57:56,080 --> 03:58:02,320 FLOW IN THE BODY CAN CAUSE 6622 03:58:02,320 --> 03:58:03,240 CERTAIN OVERFLOW. 6623 03:58:03,240 --> 03:58:04,200 THIS IS OUTSIDE THE SCOPE OF 6624 03:58:04,200 --> 03:58:04,920 THIS DOCK. 6625 03:58:04,920 --> 03:58:08,360 A YEAR AGO, I'VE BEEN CONTACTED 6626 03:58:08,360 --> 03:58:18,360 BY THE HEART DOCTOR AND THEY 6627 03:58:18,360 --> 03:58:22,280 SUGGESTED TO START THE NEW 6628 03:58:22,280 --> 03:58:23,440 NETTING OF THE THE LYMPHATIC 6629 03:58:23,440 --> 03:58:29,760 SYSTEM AS PART OF HUBMAP AND IT 6630 03:58:29,760 --> 03:58:32,160 STARTS WITH THIS TO CREATE A 6631 03:58:32,160 --> 03:58:34,400 LYMPHATIC VESSEL MAPPING. 6632 03:58:34,400 --> 03:58:36,160 WE SCRATCH OUR HEADS AND WE 6633 03:58:36,160 --> 03:58:38,880 DISCOVERED THIS OLD BOOK FROM 6634 03:58:38,880 --> 03:58:44,400 1938 AND DECIDED TO SUMMARIZE 6635 03:58:44,400 --> 03:58:47,040 THIS BOOK THAT IS PRIMARILY TEXT 6636 03:58:47,040 --> 03:58:49,280 AND NEW IMAGES INTO THIS MAPPING 6637 03:58:49,280 --> 03:58:51,320 AND OUR WORK WAS VERY FORTUNATE 6638 03:58:51,320 --> 03:58:56,240 TO WORK WITH ROBIN WHO SPENT 6639 03:58:56,240 --> 03:58:58,000 DAYS AND DAYS CATEGORIZING ALL 6640 03:58:58,000 --> 03:58:59,560 THIS LYMPHATIC SYSTEM AND THAT'S 6641 03:58:59,560 --> 03:59:00,520 HOW THE BOOK PRESENTS. 6642 03:59:00,520 --> 03:59:04,320 YOU CAN SEE WE DID A MAP AND OUR 6643 03:59:04,320 --> 03:59:07,960 JOKE WAS TO PRIMARILY SUMMARIZE 6644 03:59:07,960 --> 03:59:11,400 THE CENTRAL LYMPHATIC SYSTEM AND 6645 03:59:11,400 --> 03:59:13,000 A DIFFERENT LYMPHATIC SYSTEM. 6646 03:59:13,000 --> 03:59:14,200 SO WHY IT'S IMPORTANT BECAUSE 6647 03:59:14,200 --> 03:59:16,960 IT'S PROVIDED A NORMAL 6648 03:59:16,960 --> 03:59:18,840 ANATOMICAL REFERENCES AND IN THE 6649 03:59:18,840 --> 03:59:20,520 FUTURE PROVIDE THE LEAST OF THE 6650 03:59:20,520 --> 03:59:22,080 LYMPHATIC SYSTEM AND SO FOR 6651 03:59:22,080 --> 03:59:23,840 EXAMPLE, THIS IS PROTEIN AND YOU 6652 03:59:23,840 --> 03:59:25,840 CAN GO TO THE MAP AND THEY 6653 03:59:25,840 --> 03:59:27,680 IMMEDIATELY YOU CAN SEE THE 6654 03:59:27,680 --> 03:59:28,640 CONNECTION BETWEEN LIVER, 6655 03:59:28,640 --> 03:59:31,560 LYMPHATIC AND INTESTINAL 6656 03:59:31,560 --> 03:59:31,840 LYMPHATIC. 6657 03:59:31,840 --> 03:59:38,120 THIS IS AN EXAMPLE OF NO ONE 6658 03:59:38,120 --> 03:59:48,400 THAT WHERE THAT. 6659 03:59:55,160 --> 03:59:58,320 >> WE CAN SEE THAT THIS IS LEAK 6660 03:59:58,320 --> 04:00:00,080 OF THE LIVER LYMPHATIC INTO LUNG 6661 04:00:00,080 --> 04:00:03,440 AND THE BRON KAI AND IMMEDIATELY 6662 04:00:03,440 --> 04:00:04,240 WE CAN PHRASE THIS COMMUNICATION 6663 04:00:04,240 --> 04:00:05,920 ON THIS MAP AND THIS IS JUST 6664 04:00:05,920 --> 04:00:11,960 FROM THE SAME REGULAR BOOKS. 6665 04:00:11,960 --> 04:00:14,280 SO, WE COMPILED THE CURRENT 6666 04:00:14,280 --> 04:00:16,000 KNOWLEDGE OF LYMPHATIC ANATOMY 6667 04:00:16,000 --> 04:00:17,440 FROM ALL SOURCES AND USING THIS 6668 04:00:17,440 --> 04:00:19,360 CURRENT IMAGING TECHNOLOGY 6669 04:00:19,360 --> 04:00:22,400 PROVIDED TO UPDATE OF EXISTING 6670 04:00:22,400 --> 04:00:27,280 KNOWLEDGE AND OF COURSE, WE NEED 6671 04:00:27,280 --> 04:00:29,240 TO CONTINUE IMAGING TECHNIQUES 6672 04:00:29,240 --> 04:00:31,080 AND HUBMAP IS THE TECHNIQUE AND 6673 04:00:31,080 --> 04:00:32,360 WE'RE FORTUNATE TO TALK ABOUT 6674 04:00:32,360 --> 04:00:33,800 THAT AND WE'VE BEEN AWARDED A 6675 04:00:33,800 --> 04:00:36,880 GRANT FROM NIH TO START THIS 6676 04:00:36,880 --> 04:00:38,560 LYMPHATIC PROGRAM AND OF COURSE, 6677 04:00:38,560 --> 04:00:39,640 THERE'S A LOT OF PEOPLE INVOLVED 6678 04:00:39,640 --> 04:00:42,520 IN THIS PROJECT. 6679 04:00:42,520 --> 04:00:45,560 IT'S JUST A SMALL GROUP OF THE 6680 04:00:45,560 --> 04:00:46,760 PEOPLE BUT THERE'S MANY, MANY 6681 04:00:46,760 --> 04:00:47,760 MORE AND THANK YOU, VERY MUCH 6682 04:00:47,760 --> 04:00:53,400 FOR YOUR ATTENTION. 6683 04:00:53,400 --> 04:00:53,680 WONDERFUL. 6684 04:00:53,680 --> 04:00:54,480 THANK YOU SO MUCH, MAX. 6685 04:00:54,480 --> 04:00:56,000 WE'LL HOLD YOUR QUESTIONS TO THE 6686 04:00:56,000 --> 04:00:56,200 END. 6687 04:00:56,200 --> 04:01:00,040 NOW WE'RE READY FOR DID YOAV 6688 04:01:00,040 --> 04:01:00,240 DORI. 6689 04:01:00,240 --> 04:01:03,800 OUR SECOND SPEAKER IS Dr. DORI 6690 04:01:03,800 --> 04:01:06,680 THE DIRECTOR THE JILL AND MARK 6691 04:01:06,680 --> 04:01:08,680 FISHMAN CENTER FOR LYMPHATIC 6692 04:01:08,680 --> 04:01:09,600 RESEARCH AT CHILDREN'S HOSPITAL 6693 04:01:09,600 --> 04:01:12,200 OF PHILADELPHIA Dr. DORY WILL 6694 04:01:12,200 --> 04:01:13,720 OUTLINE NOVEL APPROACHES FOR 6695 04:01:13,720 --> 04:01:15,120 CLINICAL IMAGING OF THE HUMAN 6696 04:01:15,120 --> 04:01:16,200 LYMPHATIC SYSTEM AND THE TITLE 6697 04:01:16,200 --> 04:01:17,760 OF HIS TALK IS LYMPHATIC FLOW 6698 04:01:17,760 --> 04:01:19,160 DISORDERS AND SYSTEMIC DISEASE 6699 04:01:19,160 --> 04:01:21,240 NEW INSIGHTS FROM NOVEL IMAGING 6700 04:01:21,240 --> 04:01:22,560 TECHNIQUES AND NEW TREATMENT 6701 04:01:22,560 --> 04:01:22,800 OPTIONS. 6702 04:01:22,800 --> 04:01:24,800 THANK YOU SO MUCH, YOAV. 6703 04:01:24,800 --> 04:01:26,200 >> THANK YOU, CAN EVERYBODY HEAR 6704 04:01:26,200 --> 04:01:26,600 ME? 6705 04:01:26,600 --> 04:01:27,720 CAN YOU HEAR ME WELL? 6706 04:01:27,720 --> 04:01:28,200 >> YES. 6707 04:01:28,200 --> 04:01:29,840 >> AWESOME. 6708 04:01:29,840 --> 04:01:30,440 GOOD. 6709 04:01:30,440 --> 04:01:31,840 EXCELLENT TALK THERE MAX, THAT 6710 04:01:31,840 --> 04:01:34,240 WAS GREAT, GREAT WORK AS ALWAYS. 6711 04:01:34,240 --> 04:01:35,560 SO FIRST OF ALL I'D LIKE TO 6712 04:01:35,560 --> 04:01:38,080 THANK THE ORGANIZERS, AGAIN, 6713 04:01:38,080 --> 04:01:41,640 THIS IS AMAZING CONFERENCE AND 6714 04:01:41,640 --> 04:01:43,920 THERE'S SO MANY QUESTIONS THAT 6715 04:01:43,920 --> 04:01:47,640 THIS KIND OF CONFERENCE OPENS. 6716 04:01:47,640 --> 04:01:50,160 I REALLY DO HAVE ANYTHING TO 6717 04:01:50,160 --> 04:01:51,560 DISCLOSE EXCEPT TO SAY I HOPE 6718 04:01:51,560 --> 04:01:53,360 THE WORK WE DO IS A FORCE FOR 6719 04:01:53,360 --> 04:01:54,640 FOOD AND I'M PART OF THAT 6720 04:01:54,640 --> 04:01:56,160 MOVEMENT AND HOPEFULLY THAT WILL 6721 04:01:56,160 --> 04:01:56,720 CONTINUE. 6722 04:01:56,720 --> 04:01:58,640 I'M GOING TO ACTUALLY CONTINUE 6723 04:01:58,640 --> 04:02:01,160 TO THE PREVIOUS CONVERSATION AND 6724 04:02:01,160 --> 04:02:02,800 WITH A LITTLE BIT OF A DIFFERENT 6725 04:02:02,800 --> 04:02:04,280 ANGLE. 6726 04:02:04,280 --> 04:02:05,960 SO, YOU KNOW, WE HAVE A LOT OF 6727 04:02:05,960 --> 04:02:07,000 PATIENTS THAT WE'RE DEALING WITH 6728 04:02:07,000 --> 04:02:08,560 NOW WHO HAVE ORGAN DYSFUNCTION 6729 04:02:08,560 --> 04:02:11,240 THAT ULTIMATELY LEADS TO 6730 04:02:11,240 --> 04:02:12,040 LYMPHATIC DYSFUNCTION. 6731 04:02:12,040 --> 04:02:13,560 WE KNOW THAT LYMPHATIC 6732 04:02:13,560 --> 04:02:14,960 DYSFUNCTION CAN LEAD TO ORGAN 6733 04:02:14,960 --> 04:02:15,880 DYSFUNCTION AND THE QUESTION IS 6734 04:02:15,880 --> 04:02:18,920 WHAT IS THE RELATIONSHIP BETWEEN 6735 04:02:18,920 --> 04:02:19,920 THESE WHO THINGS? 6736 04:02:19,920 --> 04:02:22,320 AND UNFORTUNATELY, FIRST OF ALL, 6737 04:02:22,320 --> 04:02:24,080 THERE'S A LOT UNKNOWN ABOUT IT 6738 04:02:24,080 --> 04:02:25,000 BECAUSE CENTRAL LYMPHATIC 6739 04:02:25,000 --> 04:02:27,160 IMAGING WAS NOT ALWAYS 6740 04:02:27,160 --> 04:02:27,400 AVAILABLE. 6741 04:02:27,400 --> 04:02:30,160 EVEN WITH NO IMAGING, IF YOU 6742 04:02:30,160 --> 04:02:32,120 KNOW THE ANATOMICAL CONNECTIONS 6743 04:02:32,120 --> 04:02:33,400 THERE'S A LOT ABOUT THESE 6744 04:02:33,400 --> 04:02:34,800 DISEASES THAT ARE NOT KNOWN. 6745 04:02:34,800 --> 04:02:36,600 THERE ARE MANY STEPS ON THE WAY. 6746 04:02:36,600 --> 04:02:38,240 SOMETIMES, YOU KNOW, ABNORMAL 6747 04:02:38,240 --> 04:02:39,640 THINGS THAT ARE CURING NOT 6748 04:02:39,640 --> 04:02:41,400 ALWAYS DIRECTLY LINKED TO EACH 6749 04:02:41,400 --> 04:02:46,280 O. AND THEOTHERAND THERE'S A LOD 6750 04:02:46,280 --> 04:02:46,720 HOW THIS WORKS. 6751 04:02:46,720 --> 04:02:50,200 IF YOU ARE DEAL WITH A LYMPHATIC 6752 04:02:50,200 --> 04:02:51,720 SICK YOU LATORRE SYSTEM, YOU 6753 04:02:51,720 --> 04:02:52,920 NEED TO CHARACTERIZE BUT YOU 6754 04:02:52,920 --> 04:02:55,920 HAVE TO BE ABLE TO CHARACTERIZE 6755 04:02:55,920 --> 04:02:57,560 FLOW AND YOU HAVE TO BE ABLE TO 6756 04:02:57,560 --> 04:02:58,520 CHARACTERIZE THE FACTORS THAT 6757 04:02:58,520 --> 04:02:59,600 ARE EFFECTING THESE THINGS 6758 04:02:59,600 --> 04:03:01,400 BECAUSE WITHOUT DOING THAT, YOU 6759 04:03:01,400 --> 04:03:03,080 WILL NOT BE ABLE TO CHARACTERIZE 6760 04:03:03,080 --> 04:03:04,400 THE DISEASES THAT YOU ARE 6761 04:03:04,400 --> 04:03:04,800 DEALING WITH. 6762 04:03:04,800 --> 04:03:07,000 I MEAN, JUST LIKE THIS IS WHAT 6763 04:03:07,000 --> 04:03:08,440 IS THE APPROACH THAT WE'VE TAKEN 6764 04:03:08,440 --> 04:03:11,240 ON THE CARDIOVASCULAR SIZE AND 6765 04:03:11,240 --> 04:03:13,040 THE SAME EXACT APPROACH IS ON 6766 04:03:13,040 --> 04:03:15,120 THE LYMPHATIC SIDE. 6767 04:03:15,120 --> 04:03:17,040 MAX SHOWED ALREADY THE TECHNIQUE 6768 04:03:17,040 --> 04:03:19,440 WE DEVELOPED HERE OF DYNAMIC 6769 04:03:19,440 --> 04:03:22,280 CONTRAST AND SO THIS IS REALLY 6770 04:03:22,280 --> 04:03:22,480 GOOD. 6771 04:03:22,480 --> 04:03:26,280 THIS IS MR DYNAMIC CONTRAST AND 6772 04:03:26,280 --> 04:03:27,920 THE GREATNESS ABOUT THIS, IT 6773 04:03:27,920 --> 04:03:29,360 ALLOWED US FOR THE FIRST TIME TO 6774 04:03:29,360 --> 04:03:31,160 SEE ANATOMY AND ALSO TO SEE HOW 6775 04:03:31,160 --> 04:03:32,560 THE FLOW PATTERNS ARE OCCURRING 6776 04:03:32,560 --> 04:03:34,720 AND THIS IS GOOD FOR LOOKING AT 6777 04:03:34,720 --> 04:03:35,880 SOME OF THE LUNG LYMPHATIC 6778 04:03:35,880 --> 04:03:36,240 STUFF. 6779 04:03:36,240 --> 04:03:38,200 IT REALLY DOESN'T SHOW US VERY 6780 04:03:38,200 --> 04:03:39,800 WELL WHAT HAPPENS IN SOME OF THE 6781 04:03:39,800 --> 04:03:41,560 OTHER IMPORTANT STREAMS. 6782 04:03:41,560 --> 04:03:42,720 UNFORTUNATELY, THERE'S REALLY NO 6783 04:03:42,720 --> 04:03:45,080 TECHNIQUE THAT IS AS GOOD AS MRI 6784 04:03:45,080 --> 04:03:47,640 AND SHOWING US DIS STAAL 6785 04:03:47,640 --> 04:03:48,520 CONNECTIONS OF DIFFERENT STREAMS 6786 04:03:48,520 --> 04:03:49,760 AND HOW THINGS ARE 6787 04:03:49,760 --> 04:03:50,880 INTERCONNECTED TO EACH OTHER. 6788 04:03:50,880 --> 04:03:52,280 WE NOW DEVELOPED THE TECHNIQUES 6789 04:03:52,280 --> 04:03:54,440 TO IMAGE ALL THE OTHER 6790 04:03:54,440 --> 04:03:56,360 COMPARTMENTS AND YOU KNOW ONE OF 6791 04:03:56,360 --> 04:04:01,360 THE IMPORTANT ONCE IS THE LIVER. 6792 04:04:01,360 --> 04:04:02,920 SO SHOWN OVER HERE WITH NORMAL 6793 04:04:02,920 --> 04:04:05,960 LOOKS LIKE AND IT IS JUST 6794 04:04:05,960 --> 04:04:07,160 INJECTION OF THE LIVER CONNECTED 6795 04:04:07,160 --> 04:04:10,320 TO THE RETRO PER TEE KNEEL AND 6796 04:04:10,320 --> 04:04:11,680 THE THORACIC DUCT GOING UP. 6797 04:04:11,680 --> 04:04:12,960 THE LAST STREAM THAT WAS REALLY 6798 04:04:12,960 --> 04:04:16,280 NOT ROUTINELY IMAGED IS REALLY 6799 04:04:16,280 --> 04:04:18,640 VERY HARD, YOU CAN IN SOME CASES 6800 04:04:18,640 --> 04:04:19,960 GET INTO LYMPH NODES IN THE MESS 6801 04:04:19,960 --> 04:04:22,080 TARRY BUT IT'S VERY RARE AND 6802 04:04:22,080 --> 04:04:24,680 IT'S INTERMITTENT AND WE NOW DO 6803 04:04:24,680 --> 04:04:27,760 IT ROUTINE AND IN OUR PATIENTS 6804 04:04:27,760 --> 04:04:30,040 AND INTRA HIP ATTIC, WE 6805 04:04:30,040 --> 04:04:31,600 PUBLISHED ABOUT SOME OF THESE 6806 04:04:31,600 --> 04:04:32,720 CONNECTIONS OF RIVER CONNECTING 6807 04:04:32,720 --> 04:04:33,960 TO DIFFERENT THINGS AND JUST 6808 04:04:33,960 --> 04:04:35,600 PUBLISHED A PAPER ABOUT THAT AND 6809 04:04:35,600 --> 04:04:37,320 HOW IT RELATES TO DYSFUNCTION OF 6810 04:04:37,320 --> 04:04:38,480 THESE DIFFERENT ORGANS AND THE 6811 04:04:38,480 --> 04:04:42,440 DIFFERENT DISEASES WE SEE AND 6812 04:04:42,440 --> 04:04:44,240 INTERNET THIS IS THE LAST ONE 6813 04:04:44,240 --> 04:04:45,680 THAT KIND OF SOLVES THE WHOLE 6814 04:04:45,680 --> 04:04:47,920 REAL MAINSTREAMS THAT ARE COMING 6815 04:04:47,920 --> 04:04:49,680 OUT OF THE CENTRAL LYMPHATIC 6816 04:04:49,680 --> 04:04:54,440 SYSTEM BECAUSE IT GIVES US THE 6817 04:04:54,440 --> 04:04:57,320 LONG ORGANS AND THIS IS ROUTINE 6818 04:04:57,320 --> 04:04:58,680 IMAGING AND WE'VE DONE MANY, 6819 04:04:58,680 --> 04:05:02,080 MANY CASES WITH THIS AND CLOSE 6820 04:05:02,080 --> 04:05:03,640 TO 100 AND THIS IS WHAT NORMAL 6821 04:05:03,640 --> 04:05:05,480 LOOKS LIKE SO THIS IS MESS TARRY 6822 04:05:05,480 --> 04:05:10,200 GOING UP AND CONNECTING TO THE 6823 04:05:10,200 --> 04:05:10,400 LEFT. 6824 04:05:10,400 --> 04:05:12,360 IN ADDITION TO THE ANATOMY AND 6825 04:05:12,360 --> 04:05:14,120 THE FLOW, AS I SAID, WE NEED TO 6826 04:05:14,120 --> 04:05:15,040 UNDERSTAND WHAT IS GOING ON AS 6827 04:05:15,040 --> 04:05:17,600 FAR AS THE DYNAMICS, AGAIN, I'M 6828 04:05:17,600 --> 04:05:18,600 A CARDIOLOGIST SO UNDERSTANDING 6829 04:05:18,600 --> 04:05:20,120 PRESSURE IS WHAT WE DO ROUTINELY 6830 04:05:20,120 --> 04:05:21,640 AND WE NEED TO BE ABLE TO 6831 04:05:21,640 --> 04:05:22,760 CHARACTERIZE THAT AND WE'VE 6832 04:05:22,760 --> 04:05:24,160 STARTED NOW CHARACTERIZING AND 6833 04:05:24,160 --> 04:05:25,320 REPORTING SOME OF THAT AND THIS 6834 04:05:25,320 --> 04:05:26,640 IS A PAPER THAT WE JUST 6835 04:05:26,640 --> 04:05:28,280 PUBLISHED WITH A COLLABORATION 6836 04:05:28,280 --> 04:05:31,720 IN DENMARK ABOUT THE SPONTANEOUS 6837 04:05:31,720 --> 04:05:33,520 CONTRACTIONS OF THE THORACIC 6838 04:05:33,520 --> 04:05:34,680 DUCT AND ANOTHER PAPER THAT IS 6839 04:05:34,680 --> 04:05:36,200 JUST GETTING PUBLISHED ABOUT 6840 04:05:36,200 --> 04:05:40,280 RESPONSE OF THORACIC DUCT TO 6841 04:05:40,280 --> 04:05:42,240 CERTAIN DIM STIMULI AND YOU CAN 6842 04:05:42,240 --> 04:05:43,800 SEE THAT PLEASURE INSIDE THE 6843 04:05:43,800 --> 04:05:45,560 THORACIC DUCT CAN RISE ABRUPTLY 6844 04:05:45,560 --> 04:05:47,280 AND STAY ELEVATED UP TO 6845 04:05:47,280 --> 04:05:48,720 40 MILLIMETERS OF MERCURY AND 6846 04:05:48,720 --> 04:05:50,680 WHAT DOES THIS MEAN? 6847 04:05:50,680 --> 04:05:52,320 IT HAS IMPLICATIONS AND THESE 6848 04:05:52,320 --> 04:05:54,480 ARE THINGS THAT WE ARE CURRENTLY 6849 04:05:54,480 --> 04:05:55,040 LEARNING. 6850 04:05:55,040 --> 04:05:56,240 THERE ARE MANY KINDS OF 6851 04:05:56,240 --> 04:05:57,640 INTERVENTIONS THAT WE DO INSIDE 6852 04:05:57,640 --> 04:05:59,080 THE LYMPHATIC DUCT. 6853 04:05:59,080 --> 04:06:01,080 SOME INCLUDES THINGS AND SOME 6854 04:06:01,080 --> 04:06:03,520 ARE DECOMPRESS THINGS AND WE 6855 04:06:03,520 --> 04:06:05,680 PUBLISHED ABOUT SURGICAL 6856 04:06:05,680 --> 04:06:06,880 DECOMPRESSION PROCEDURES. 6857 04:06:06,880 --> 04:06:08,880 THOSE WORKED BUT WE HAVE TO BE 6858 04:06:08,880 --> 04:06:10,640 ABLE TO UNDERSTAND BASED ON THE 6859 04:06:10,640 --> 04:06:11,520 SUBSTRATE WE'RE DEALING WITH 6860 04:06:11,520 --> 04:06:13,240 WHICH OF THESE IS GOING TO WORK 6861 04:06:13,240 --> 04:06:13,600 BETTER. 6862 04:06:13,600 --> 04:06:15,360 SO I WON'T BE ABLE TO TALK ABOUT 6863 04:06:15,360 --> 04:06:17,400 OBVIOUSLY ALL THE ORGANS AND 6864 04:06:17,400 --> 04:06:18,920 JUST DEALING WITH LET'S SAY LUNG 6865 04:06:18,920 --> 04:06:20,160 DISEASE AND WE'LL TAKE THAT AS 6866 04:06:20,160 --> 04:06:23,360 AN EXAMPLE AND WE HAVE MEET OWE 6867 04:06:23,360 --> 04:06:34,320 NATNEONATAL LUNGDISEASE AND IT E 6868 04:06:34,320 --> 04:06:35,160 RESPIRATORY SUPPORT. 6869 04:06:35,160 --> 04:06:37,000 SOME OF THESE BABIES STARTS A 6870 04:06:37,000 --> 04:06:39,680 CYCLE OF INCREASE INEXTRA 6871 04:06:39,680 --> 04:06:41,520 THORACIC PRESSURE, INCREASED CDP 6872 04:06:41,520 --> 04:06:43,440 AND THOSE TWO LEAD TO LYMPHATIC 6873 04:06:43,440 --> 04:06:45,240 DYSFUNCTION AND AGAIN WE HAVE 6874 04:06:45,240 --> 04:06:47,680 BABIES WITH HIGH CVP OR WHO 6875 04:06:47,680 --> 04:06:50,320 DON'T DO THIS BUT SOME DO THIS 6876 04:06:50,320 --> 04:06:53,840 AND WHEN LYMPHATIC DYSFUNCTION 6877 04:06:53,840 --> 04:06:55,040 OCCURS, THEY DEVELOP INFLATIONS 6878 04:06:55,040 --> 04:06:57,400 AND OTHER THINGS, TISSUE EDEMA, 6879 04:06:57,400 --> 04:06:59,400 AND THIS ULTIMATELY LEADS TO 6880 04:06:59,400 --> 04:07:01,200 WORSENING OF THE RESPIRATORY AND 6881 04:07:01,200 --> 04:07:03,800 THEY JUST START CIRCLING THE 6882 04:07:03,800 --> 04:07:05,160 DRAIN AND MOST OF THEM IT LEADS 6883 04:07:05,160 --> 04:07:05,960 TO DEATH. 6884 04:07:05,960 --> 04:07:08,200 BUT WE CAN INTERVEN AND STOP 6885 04:07:08,200 --> 04:07:10,800 THIS PSYCHE MANY USING VERY 6886 04:07:10,800 --> 04:07:21,280 SPECIAL INTERVENTIONS IS ALL 6887 04:07:25,440 --> 04:07:26,760 THE CHANNELS ARE EVERYWHERE BUT 6888 04:07:26,760 --> 04:07:28,560 YOU CAN SEE HERE THAT THE 6889 04:07:28,560 --> 04:07:30,320 THORACIC DUCT IS EXTRAORDINARY 6890 04:07:30,320 --> 04:07:32,200 DIE A LATED AND SHOULD BE 6891 04:07:32,200 --> 04:07:33,400 DRAINING TO THE VEIN. 6892 04:07:33,400 --> 04:07:34,920 INSTEAD IT'S FLOWING INTO THIS 6893 04:07:34,920 --> 04:07:36,040 CHILD'S HEAD AND THE CHILD'S 6894 04:07:36,040 --> 04:07:38,720 HEAD IS ENORMOUS AND YOU CAN SEE 6895 04:07:38,720 --> 04:07:41,320 WHEN WE ALTER THE RESPIRATORY 6896 04:07:41,320 --> 04:07:49,280 STUFF, SO WE LOWER SO THIS 6897 04:07:49,280 --> 04:07:51,520 SHOULD BE NON PUBLICATION 6898 04:07:51,520 --> 04:07:55,080 HOPEFULLY SOL SOON. 6899 04:07:55,080 --> 04:08:04,520 THIS IS CAUSING THE DOUG DUCT NO 6900 04:08:04,520 --> 04:08:04,880 DRAIN. 6901 04:08:04,880 --> 04:08:08,320 THEY HAVE A MULTI COMPORTMENT 6902 04:08:08,320 --> 04:08:09,760 LYMPHATIC SYSTEM. 6903 04:08:09,760 --> 04:08:13,040 DIFFERENT PARTS OF THE LYMPH ARE 6904 04:08:13,040 --> 04:08:13,440 FAILING. 6905 04:08:13,440 --> 04:08:14,960 SOMETHING IS WRONG THAT IS 6906 04:08:14,960 --> 04:08:16,960 CHALLENGING THEIR LYMPH SYSTEM 6907 04:08:16,960 --> 04:08:18,480 AND ONE OF THEM IS THIS 6908 04:08:18,480 --> 04:08:20,040 FUNCTIONAL THORACIC OBSTRUCTION 6909 04:08:20,040 --> 04:08:23,080 AND THIS IS WHAT LUNG DISEASE 6910 04:08:23,080 --> 04:08:25,720 DOES AND IT'S OBSTRUCTING THE 6911 04:08:25,720 --> 04:08:26,000 OUTLET. 6912 04:08:26,000 --> 04:08:29,040 BUT IT DOESN'T WHEN IT DOES 6913 04:08:29,040 --> 04:08:31,320 THAT, IT ALTERS THE FLOW OF THE 6914 04:08:31,320 --> 04:08:34,960 DIFFERENT SYSTEMS SO HERE IS YOU 6915 04:08:34,960 --> 04:08:37,760 CAN SEE EVEN THOUGH THE ACCESS 6916 04:08:37,760 --> 04:08:39,600 WAS GOOD THERE'S A LITTLE BIT OF 6917 04:08:39,600 --> 04:08:41,080 A LEAK INTO THE INTESTINE HERE 6918 04:08:41,080 --> 04:08:43,800 BUT IT IS NOT LIGHTING UP AT ALL 6919 04:08:43,800 --> 04:08:46,520 SO THERE'S NO FLOW OUT INTO THE 6920 04:08:46,520 --> 04:08:47,400 THORACIC DUCT WHICH IS WHAT IT 6921 04:08:47,400 --> 04:08:48,760 IS SUPPOSED TO DO. 6922 04:08:48,760 --> 04:08:50,440 AND THAT HAS IMPLICATIONS. 6923 04:08:50,440 --> 04:08:54,080 AND HERE IS THE IMAGING IN THIS 6924 04:08:54,080 --> 04:08:55,880 KID AND THE INTESTACY TINS ARE 6925 04:08:55,880 --> 04:08:57,520 FILLING QUICKLY SO THIS IS 6926 04:08:57,520 --> 04:08:59,240 SEVERE PROTEIN LOSING AND THERE 6927 04:08:59,240 --> 04:09:00,240 ARE CONNECTIONS FROM THE LIVER 6928 04:09:00,240 --> 04:09:02,080 UP INTO THE LUNG BUT AGAIN 6929 04:09:02,080 --> 04:09:07,560 AUTHORIZE AUCTTHORACICDUCT IS N. 6930 04:09:07,560 --> 04:09:09,840 AND IT LIGHTS UP THE DUCT AND 6931 04:09:09,840 --> 04:09:12,320 LIGHTS UP A WHOLE BUNCH OF OTHER 6932 04:09:12,320 --> 04:09:12,800 STUFF. 6933 04:09:12,800 --> 04:09:13,880 THE BLACK FLOW IN THE SKIN AND 6934 04:09:13,880 --> 04:09:14,920 ALL THOSE THINGS. 6935 04:09:14,920 --> 04:09:18,680 AND THIS IS WHAT IT LOOKS LIKE 6936 04:09:18,680 --> 04:09:22,440 LATER ON IN HIGHER RESOLUTION 6937 04:09:22,440 --> 04:09:22,680 IMAGING. 6938 04:09:22,680 --> 04:09:24,280 THESE FINDINGS HAVE IMPLICATIONS 6939 04:09:24,280 --> 04:09:25,400 BECAUSE ONE OF THE FINDINGS IN 6940 04:09:25,400 --> 04:09:27,000 THESE KIDS IS THEY CAN'T BE FED. 6941 04:09:27,000 --> 04:09:30,920 THEY CAN'T EAT. 6942 04:09:30,920 --> 04:09:36,520 IF THEY CONDITION DRIVEN INTO CA 6943 04:09:36,520 --> 04:09:36,720 PROBLEM. 6944 04:09:36,720 --> 04:09:38,760 THEY HAVE PROBLEM LOSING THEY 6945 04:09:38,760 --> 04:09:40,280 HAVE A HUGE CHANNEL GOING IN THE 6946 04:09:40,280 --> 04:09:41,880 SKIN AND GOING ALL OVER THE 6947 04:09:41,880 --> 04:09:44,120 PLACE, AND SO, THESE THINGS 6948 04:09:44,120 --> 04:09:45,720 MATTER ULTIMATELY WHAT IS GOING 6949 04:09:45,720 --> 04:09:49,040 ON IN THERE. 6950 04:09:49,040 --> 04:09:49,400 CLINICALLY. 6951 04:09:49,400 --> 04:09:51,200 TO SHOW YOU HOW WE CAN BREAK THE 6952 04:09:51,200 --> 04:09:51,400 CYCLE. 6953 04:09:51,400 --> 04:09:53,440 THIS IS A CHILD WITH SEVERE LUNG 6954 04:09:53,440 --> 04:09:54,960 DISEASE, ABNORMAL CENTRAL FLOW. 6955 04:09:54,960 --> 04:09:56,600 NO ABNORMAL VARIANT HERE JUST 6956 04:09:56,600 --> 04:09:59,200 FLOWING INTO THE HEAD BECAUSE IT 6957 04:09:59,200 --> 04:09:59,480 CAN'T DRAIN. 6958 04:09:59,480 --> 04:10:00,360 WE DID SEVERAL PROCEDURES ON 6959 04:10:00,360 --> 04:10:01,880 THIS BABY AND OBSTRUCTED THE 6960 04:10:01,880 --> 04:10:03,440 FLOW GOING INTO THE HEAD AND THE 6961 04:10:03,440 --> 04:10:04,520 CHANNEL GOING INTO THE HEAD WAS 6962 04:10:04,520 --> 04:10:06,360 MUCH BIGGER THAN THE NORMAL 6963 04:10:06,360 --> 04:10:07,560 CHANNEL THAT WAS CONNECTED TO 6964 04:10:07,560 --> 04:10:09,560 THE VEIN SO WE REROUTED THE FLOW 6965 04:10:09,560 --> 04:10:10,560 GOING INTO THE VEIN. 6966 04:10:10,560 --> 04:10:14,400 AS SOON AS WE DO THAT, THE 6967 04:10:14,400 --> 04:10:16,440 CHILD'S HEAD GOES DOWN AND EDEMA 6968 04:10:16,440 --> 04:10:18,120 GOES DOWN AND THE LUNG DISEASE 6969 04:10:18,120 --> 04:10:22,280 IS CHANGING BECAUSE THE CHILD IS 6970 04:10:22,280 --> 04:10:22,600 PEEP. 6971 04:10:22,600 --> 04:10:27,120 SO IT'S REVERSED AND THE CHILD 6972 04:10:27,120 --> 04:10:30,400 GETS BETTER AND WE TAKE A CHILD 6973 04:10:30,400 --> 04:10:31,840 FROM LIFE-THREATENING AND THEY 6974 04:10:31,840 --> 04:10:32,080 SURVIVE. 6975 04:10:32,080 --> 04:10:34,200 WE CAN DO THAT BY UNDERSTANDING 6976 04:10:34,200 --> 04:10:35,880 THESE DIFFERENT THINGS. 6977 04:10:35,880 --> 04:10:37,160 NOW, CHRONIC LUNG DISEASE, ONE 6978 04:10:37,160 --> 04:10:39,080 OF THE PARTS OF CHRONIC LUNG 6979 04:10:39,080 --> 04:10:42,040 DISEASE IS PULMONARY EDEMA SO 6980 04:10:42,040 --> 04:10:43,360 IT'S A LYMPHATIC DYSFUNCTION. 6981 04:10:43,360 --> 04:10:45,520 WE DON'T MOW MUCH ABOUT THAT IS 6982 04:10:45,520 --> 04:10:47,320 WHAT IS LYMPHATIC DOING EVEN IF 6983 04:10:47,320 --> 04:10:49,760 THEY'RE FLOWING, AND A CHILD 6984 04:10:49,760 --> 04:10:51,000 THAT HAS AN LUNG LIKE THAT BUT 6985 04:10:51,000 --> 04:10:52,760 WITH YOU KNOW THAT DOING CERTAIN 6986 04:10:52,760 --> 04:10:54,000 PROCEDURES AND INTERVENTIONS CAN 6987 04:10:54,000 --> 04:10:55,200 TAKE A CHILD WITH LUNGS LIKE 6988 04:10:55,200 --> 04:11:00,120 THAT TO THIS WHERE LUNG DISEASE 6989 04:11:00,120 --> 04:11:00,400 IMPROVES. 6990 04:11:00,400 --> 04:11:01,240 THE CHEST X-RAY IS NOT WET BUT 6991 04:11:01,240 --> 04:11:02,440 WHAT ARE THEY DOING IN THE 6992 04:11:02,440 --> 04:11:04,160 DIFFERENT PICTURES OVER HERE, 6993 04:11:04,160 --> 04:11:09,360 IT'S SOMETHING THAT WE DON'T 6994 04:11:09,360 --> 04:11:15,560 COMPLETELY UNDERSTAND. 6995 04:11:15,560 --> 04:11:17,520 LYMPH DYSFUNCTION CAN CAUSE 6996 04:11:17,520 --> 04:11:18,640 ORGAN DYSFUNCTION AND NO BETTER 6997 04:11:18,640 --> 04:11:20,160 IS THE EXAMPLES OF THESE 6998 04:11:20,160 --> 04:11:20,400 PATIENTS. 6999 04:11:20,400 --> 04:11:22,360 I KNOW PEOPLE TALKED ABOUT KLA 7000 04:11:22,360 --> 04:11:23,520 YESTERDAY BUT THIS IS A GIRL 7001 04:11:23,520 --> 04:11:25,640 WITH KLA AND WE PUBLISHED ABOUT 7002 04:11:25,640 --> 04:11:28,000 THIS WHO PRESENTED WITH US WITH 7003 04:11:28,000 --> 04:11:30,680 SEVERE PULMONARY DYSFUNCTION SO 7004 04:11:30,680 --> 04:11:32,240 HER FUNCTION TEST YOU CAN SEE 7005 04:11:32,240 --> 04:11:33,640 OVER HERE WERE HALF NORMAL AND 7006 04:11:33,640 --> 04:11:35,600 SHE COULD BARELY WALK A CROSS 7007 04:11:35,600 --> 04:11:36,040 THE ROOM. 7008 04:11:36,040 --> 04:11:37,840 SHE HAD TO QUIT COLLEGE. 7009 04:11:37,840 --> 04:11:38,760 EVERYTHING THAT WE UNDERSTOOD 7010 04:11:38,760 --> 04:11:41,080 ABOUT LUNG DISEASE, TURNED OUT 7011 04:11:41,080 --> 04:11:44,560 TO BE WRONG AND WE PUT HER ON 7012 04:11:44,560 --> 04:11:46,520 THE DRUG AND SHE WITHIN A FEW 7013 04:11:46,520 --> 04:11:48,160 WEEKS NORMALIZED HER LUNG 7014 04:11:48,160 --> 04:11:51,000 FUNCTION SO LUNG FUNCTION, EVEN 7015 04:11:51,000 --> 04:11:52,560 THROW HAD HE LIVED FOR 23 YEARS 7016 04:11:52,560 --> 04:11:55,280 WITH HORRIBLE LUNG FUNCTION, IT 7017 04:11:55,280 --> 04:11:58,200 IMMEDIATELY REVERSES. 7018 04:11:58,200 --> 04:11:59,480 ALL HER SYMPTOMS GO AWAY AND 7019 04:11:59,480 --> 04:12:01,320 THIS IS WHAT IT LOOKS LIKE. 7020 04:12:01,320 --> 04:12:03,400 HERE IS HER INFUSIONS AND HER CT 7021 04:12:03,400 --> 04:12:05,560 IS NORMAL AND CENTRAL LYMPH 7022 04:12:05,560 --> 04:12:07,360 SYSTEM IS NORMALIZING AND YOU 7023 04:12:07,360 --> 04:12:09,560 CAN SEE THAT ALL THE PRO FUSION 7024 04:12:09,560 --> 04:12:11,280 SHE HAD BEFORE AND WE DIDN'T DO 7025 04:12:11,280 --> 04:12:13,080 ANY INTERVENTIONS OTHER THAN 7026 04:12:13,080 --> 04:12:16,280 PUTTING HER ON A DRUG AND 7027 04:12:16,280 --> 04:12:17,680 REMODELING HER LYMPHATIC AND ALL 7028 04:12:17,680 --> 04:12:19,560 THE STUFF FLOODING THE LUNG AND 7029 04:12:19,560 --> 04:12:22,280 ALL THE ABNORMAL FLOW IS GONE. 7030 04:12:22,280 --> 04:12:25,000 HER T2MRI OF HER CHEST 7031 04:12:25,000 --> 04:12:25,920 NORMALIZED COMPLETELY AND THE 7032 04:12:25,920 --> 04:12:27,480 GIRL WHO COULD NOT WALK A CROSS 7033 04:12:27,480 --> 04:12:30,400 THE ROOM, RUNS A 5K MARATHON 7034 04:12:30,400 --> 04:12:31,520 THREE MONTHS AFTER STARTING THE 7035 04:12:31,520 --> 04:12:33,400 DRUG AND NOW PRACTICING FOR A 7036 04:12:33,400 --> 04:12:34,800 10K MARATHON, SO THINGS 7037 04:12:34,800 --> 04:12:36,000 COMPLETELY REVERSED. 7038 04:12:36,000 --> 04:12:37,560 THIS IS KIND OF A PARADIGM SHIFT 7039 04:12:37,560 --> 04:12:38,800 IN THE WAY WE WERE THINKING 7040 04:12:38,800 --> 04:12:40,680 ABOUT IT BECAUSE WE THOUGHT, YOU 7041 04:12:40,680 --> 04:12:44,080 KNOW, LUNG DISEASE IS BAD AND IT 7042 04:12:44,080 --> 04:12:46,000 GETS FIXED BUT STANA LEWDED TO 7043 04:12:46,000 --> 04:12:47,200 THAT BEFORE YOU KNOW, THINGS ARE 7044 04:12:47,200 --> 04:12:48,720 NOT EXACTLY COMPLETELY FIXED AND 7045 04:12:48,720 --> 04:12:50,240 NOT COMPLETELY REVERSIBLE AND I 7046 04:12:50,240 --> 04:12:52,240 THINK THERE'S A LOT MORE THAT WE 7047 04:12:52,240 --> 04:12:53,400 NEED TO DO TO UNDERSTAND. 7048 04:12:53,400 --> 04:12:54,920 WHAT IS REVERSIBLE AND WHAT IS 7049 04:12:54,920 --> 04:12:58,160 NOT AND WHAT WE CALL LUNG 7050 04:12:58,160 --> 04:12:58,600 DISEASE. 7051 04:12:58,600 --> 04:13:00,560 THERE ARE CASE WHO'S HAVE THIS 7052 04:13:00,560 --> 04:13:01,440 ANATOMICAL VARIANT. 7053 04:13:01,440 --> 04:13:03,320 THIS PULMONARY PRO FUSION STUFF. 7054 04:13:03,320 --> 04:13:04,600 WHEN YOU TAKE A CHILD WHO HAS 7055 04:13:04,600 --> 04:13:06,720 THAT EX YOU CHALLENGE THEM WITH 7056 04:13:06,720 --> 04:13:09,200 HEART DISEASE WHICH IS THIS KID, 7057 04:13:09,200 --> 04:13:10,480 THINGS GET BAD. 7058 04:13:10,480 --> 04:13:12,040 OBVIOUSLY THEY CAN'T HANDLE THE 7059 04:13:12,040 --> 04:13:13,920 FLOW THAT IS GOING TOWARDS THE 7060 04:13:13,920 --> 04:13:14,240 LUNG. 7061 04:13:14,240 --> 04:13:15,560 BUT WITHOUT HEART DISEASE, THEY 7062 04:13:15,560 --> 04:13:17,120 ARE ABLE TO HANDLE THE FLOW AND 7063 04:13:17,120 --> 04:13:18,280 WE DON'T COMPLETELY UNDERSTAND 7064 04:13:18,280 --> 04:13:21,160 HOW CAN THEY DO THAT. 7065 04:13:21,160 --> 04:13:23,280 THIS CHILD WHO HAS HEART DISEASE 7066 04:13:23,280 --> 04:13:24,800 ALSO WAS CALLED CHRONIC LUNG 7067 04:13:24,800 --> 04:13:26,400 DISEASE BUT HE DID NOT HAVE 7068 04:13:26,400 --> 04:13:27,840 CHRONIC LUNG DISEASE BECAUSE IF 7069 04:13:27,840 --> 04:13:29,720 YOU INTERVENE AND STOP THE FLOW 7070 04:13:29,720 --> 04:13:33,320 TO TOTHE LUNGS, THIS HAPPENED TS 7071 04:13:33,320 --> 04:13:37,080 CHILD SO HIS RESPIRATORY SUPPORT 7072 04:13:37,080 --> 04:13:38,240 NORMALIZES AND THE CHILD GETS 7073 04:13:38,240 --> 04:13:39,320 DISCHARGED FROM THE HOSPITAL BUT 7074 04:13:39,320 --> 04:13:41,240 HE HAS HEART DISEASE AND 7075 04:13:41,240 --> 04:13:43,640 LYMPHATIC DYSFUNCTION ULTIMATELY 7076 04:13:43,640 --> 04:13:44,840 DEVELOPING DYSFUNCTION AND 7077 04:13:44,840 --> 04:13:46,840 ULTIMATELY NEEDS A HEART 7078 04:13:46,840 --> 04:13:47,240 TRANSPLANT. 7079 04:13:47,240 --> 04:13:49,080 BUT AGAIN, THERE'S A REVERSE 7080 04:13:49,080 --> 04:13:50,720 ABILITY AND SOME OF WHAT WE'RE 7081 04:13:50,720 --> 04:13:51,680 LOOKING AT OVER NOW. 7082 04:13:51,680 --> 04:13:54,000 TO REALLY UNDERSTAND ALL OF 7083 04:13:54,000 --> 04:13:55,120 THIS, ONE THING WE NEED TO 7084 04:13:55,120 --> 04:13:56,320 UNDERSTAND IS THE PHENOTYPE AND 7085 04:13:56,320 --> 04:13:59,280 THE IMAGING HELPS US DO THAT, 7086 04:13:59,280 --> 04:13:59,480 RIGHT. 7087 04:13:59,480 --> 04:14:02,120 WE NEED TO UNDERSTAND THE 7088 04:14:02,120 --> 04:14:03,680 LYMPHATIC DYNAMICS, WHATEVER YOU 7089 04:14:03,680 --> 04:14:04,480 WANT TO CALL THEM. 7090 04:14:04,480 --> 04:14:05,680 WE NEED TO UNDERSTAND THE 7091 04:14:05,680 --> 04:14:07,960 SUBSTRATE AND THE GENOTYPE AND 7092 04:14:07,960 --> 04:14:11,080 THE CHANNELS DOING THAT ALLOWS 7093 04:14:11,080 --> 04:14:14,200 CERTAIN KIDS TO DEVELOP THIS 7094 04:14:14,200 --> 04:14:16,000 FUNCTION AND OTHER KIDS DO NOT 7095 04:14:16,000 --> 04:14:17,400 DEVELOP THIS FUNCTION. 7096 04:14:17,400 --> 04:14:18,240 ANDMENT MATILY WHEN WE 7097 04:14:18,240 --> 04:14:19,560 UNDERSTAND BOTH OF THESE WE'LL 7098 04:14:19,560 --> 04:14:21,040 BE ABLE TO DEVELOP THE TOOLS 7099 04:14:21,040 --> 04:14:23,960 THAT WILL LAW US TO TREATMENT 7100 04:14:23,960 --> 04:14:24,280 THESE THINGS. 7101 04:14:24,280 --> 04:14:26,160 WE STARTED ADDRESSING THIS 7102 04:14:26,160 --> 04:14:27,400 TOGETHER WITH THE SARAH WHO IS 7103 04:14:27,400 --> 04:14:29,880 NOW IN THE NIH, A CLOSE FRIEND 7104 04:14:29,880 --> 04:14:31,320 AND COLLABORATOR BY LOOKING AT 7105 04:14:31,320 --> 04:14:33,800 THE GENOTYPE-PHENOTYPE 7106 04:14:33,800 --> 04:14:36,120 CORRELATION AND SHE JUST 7107 04:14:36,120 --> 04:14:41,040 PUBLISHED THIS PAPER. 7108 04:14:41,040 --> 04:14:42,000 IF THIS IS YOUR GENE, THIS IS 7109 04:14:42,000 --> 04:14:43,840 WHAT YOUR ANATOMY LOOKS LOOK AND 7110 04:14:43,840 --> 04:14:45,600 WE CAN TAKE THIS AND TRANSLATE 7111 04:14:45,600 --> 04:14:50,000 IT, IF THIS IS WHAT YOUR ANATOMY 7112 04:14:50,000 --> 04:14:52,400 WILL LOOK WHAT ARE THE ORGAN 7113 04:14:52,400 --> 04:14:53,600 DYSFUNCTIONS THAT ARE GOING TO 7114 04:14:53,600 --> 04:14:55,000 LEAD TO DYSFUNCTION IN THIS 7115 04:14:55,000 --> 04:14:59,520 SYSTEM THAT ULTIMAT ULTIMATELY D 7116 04:14:59,520 --> 04:15:00,680 TO THE SYMPTOMS. 7117 04:15:00,680 --> 04:15:02,440 I'LL END BY JUST SUMMARIZING 7118 04:15:02,440 --> 04:15:03,680 THAT AS FAR AS GAPS AND 7119 04:15:03,680 --> 04:15:05,240 OPPORTUNITIES, I MEAN, THIS IS 7120 04:15:05,240 --> 04:15:07,480 LITERALLY ENDLESS BECAUSE 7121 04:15:07,480 --> 04:15:08,720 THERE'S SO MUCH WE DON'T KNOW 7122 04:15:08,720 --> 04:15:09,360 OVER HERE. 7123 04:15:09,360 --> 04:15:11,520 AGAIN, WE DON'T KNOW HOW ORGANS 7124 04:15:11,520 --> 04:15:12,680 ARE EFFECTING LYMPHATICS AND 7125 04:15:12,680 --> 04:15:16,160 WHAT ARE THE LYMPHATICS 7126 04:15:16,160 --> 04:15:18,000 SUBSTRATES THAT -- EVEN 7127 04:15:18,000 --> 04:15:20,160 LYMPHATIC SUBSTRATE, WE DON'T 7128 04:15:20,160 --> 04:15:22,200 UNDERSTAND EXACTLY WHAT THAT IS. 7129 04:15:22,200 --> 04:15:22,840 YOU KNOW. 7130 04:15:22,840 --> 04:15:24,480 THE SYMPTOMS MIGHT BE THE SAME. 7131 04:15:24,480 --> 04:15:26,480 BUT IN ONE IT MIGHT BE A WALL 7132 04:15:26,480 --> 04:15:28,240 PROBLEM, A PUMPING PROBLEM OR 7133 04:15:28,240 --> 04:15:29,480 VALVE PROBLEM AND ON THE OTHER 7134 04:15:29,480 --> 04:15:32,240 HAND WE NEED TO UNDERSTAND WHAT 7135 04:15:32,240 --> 04:15:33,040 LIMBS GET DYSFUNCTIONAL INSIDE 7136 04:15:33,040 --> 04:15:34,680 OF AN ORGAN SYSTEM HOW IT 7137 04:15:34,680 --> 04:15:36,360 EFFECTS THE ORGAN AND THAT CAN 7138 04:15:36,360 --> 04:15:38,040 BE REVERSIBLE AND WE NEED TO 7139 04:15:38,040 --> 04:15:38,960 DEVELOP BETTER TREATMENT OPTIONS 7140 04:15:38,960 --> 04:15:40,760 FOR THESE KIND OF PATIENTS WITH 7141 04:15:40,760 --> 04:15:42,160 THESE KINDS OF DISORDERS AND 7142 04:15:42,160 --> 04:15:43,880 I'LL END BY SAYING THANK YOU, 7143 04:15:43,880 --> 04:15:45,400 IT'S VERY MUCH FOR IN INVITING 7144 04:15:45,400 --> 04:15:46,160 ME TO THIS. 7145 04:15:46,160 --> 04:15:47,960 IT'S AN AWESOME CONFERENCE AND I 7146 04:15:47,960 --> 04:15:49,360 HOPE WE GET TO WORK TOGETHER IN 7147 04:15:49,360 --> 04:15:50,000 THE FUTURE. 7148 04:15:50,000 --> 04:15:51,320 THERE'S MANY PROJECTS THAT WE 7149 04:15:51,320 --> 04:15:52,600 CAN DO TOGETHER ON THIS KIND OF 7150 04:15:52,600 --> 04:15:58,120 STUFF SO THANK YOU. 7151 04:15:58,120 --> 04:16:03,240 >> THANK YOU SO MUCH, YOAV, THAT 7152 04:16:03,240 --> 04:16:05,280 WAS REALLY INSPIRING AND 7153 04:16:05,280 --> 04:16:06,760 EXCITING NEWS TO HEAR ABOUT 7154 04:16:06,760 --> 04:16:08,560 BREANNE A WE WILL TURN IT OVER 7155 04:16:08,560 --> 04:16:11,320 TO Dr. NILS GEHLENBORG OUR 7156 04:16:11,320 --> 04:16:14,120 THIRD SPEAKER OF THE SESSION. 7157 04:16:14,120 --> 04:16:15,720 AN SO HE IS SEE AT PROFESSOR AT 7158 04:16:15,720 --> 04:16:17,440 HARD SAD MEDICAL SCHOOL WHO 7159 04:16:17,440 --> 04:16:18,480 ADDITIONALLY DIRECTS THE MASTER 7160 04:16:18,480 --> 04:16:22,720 OF BIOMEDICAL INFORMATICS 7161 04:16:22,720 --> 04:16:24,040 PROGRAM. 7162 04:16:24,040 --> 04:16:26,320 HE VISUALIZES SINGLE CELL AND 7163 04:16:26,320 --> 04:16:27,720 CLINICAL TITLE AND THE TITLE OF 7164 04:16:27,720 --> 04:16:30,240 HIS TALK IS INGRATE TIVE 7165 04:16:30,240 --> 04:16:31,480 VISUALIZATION OF SPATIALLY 7166 04:16:31,480 --> 04:16:34,640 RESOLVED SINGLE CELL DATA AND 7167 04:16:34,640 --> 04:16:38,280 LYMPHATIC TISSUE. 7168 04:16:38,280 --> 04:16:41,760 THANK YOU, NILS. 7169 04:16:41,760 --> 04:16:52,320 YOU ARE STILL MUTED. 7170 04:16:52,320 --> 04:16:53,720 >> ALL RIGHT. 7171 04:16:53,720 --> 04:16:55,840 I'M NO LONGER MUTED. 7172 04:16:55,840 --> 04:16:56,120 APOLOGIES. 7173 04:16:56,120 --> 04:16:58,640 I WAS GOING TO START BY SAYING 7174 04:16:58,640 --> 04:17:02,320 THANK YOU VERY MUCH FOR THE 7175 04:17:02,320 --> 04:17:03,600 INVITATION, ANDREA AND ALL THE 7176 04:17:03,600 --> 04:17:06,040 OTHER ORGANIZERS WHO HAVE WORKED 7177 04:17:06,040 --> 04:17:07,840 VERY HARD, I THINK, ON PUTTING 7178 04:17:07,840 --> 04:17:08,960 TOGETHER THIS AMAZING PROGRAM 7179 04:17:08,960 --> 04:17:11,280 FOR THIS MEETING. 7180 04:17:11,280 --> 04:17:19,920 I SHOULD REALLY DISCLOSE THAT I 7181 04:17:19,920 --> 04:17:21,400 HAVE LITTLE IN SIGHT INTO 7182 04:17:21,400 --> 04:17:21,840 LYMPHATICS. 7183 04:17:21,840 --> 04:17:23,680 I'M A DATA VISUALIZATION EXPERT. 7184 04:17:23,680 --> 04:17:25,200 AND I WANT TO TELL YOU A LITTLE 7185 04:17:25,200 --> 04:17:27,160 BIT ABOUT DATA VISUALIZATION AND 7186 04:17:27,160 --> 04:17:29,360 I'M BEEN INSPIRED WHAT I HEARD 7187 04:17:29,360 --> 04:17:32,600 HERE YESTERDAY AND TODAY. 7188 04:17:32,600 --> 04:17:34,240 SO, MY TALK IS ABOUT THE 7189 04:17:34,240 --> 04:17:35,360 INTEGRATION TIVE VISH YOUIZATION 7190 04:17:35,360 --> 04:17:38,120 OF MULTI MODAL AND 7191 04:17:38,120 --> 04:17:39,280 SPATIALLY-RESOLVED SINGLE-CELL 7192 04:17:39,280 --> 04:17:41,040 DATA IN LYMPHATIC TISSUE AND I 7193 04:17:41,040 --> 04:17:42,720 WILL TROY TO GIVE YOU A LITTLE 7194 04:17:42,720 --> 04:17:44,720 BIT OF A PERSPECTIVE FROM MY 7195 04:17:44,720 --> 04:17:52,880 WORK IN VARIOUS CELL ATLAS 7196 04:17:52,880 --> 04:17:59,680 PROJECTS. 7197 04:17:59,680 --> 04:18:01,480 I'M PART OF THE CONSORTIUM AND I 7198 04:18:01,480 --> 04:18:06,080 HAVE LED THIS DEVELOPMENT OF 7199 04:18:06,080 --> 04:18:16,600 VISUALIZE SOFT MANY HAVE HARD 7200 04:18:17,440 --> 04:18:19,040 PREVIOUS TALKS AND I WAS VERY 7201 04:18:19,040 --> 04:18:20,920 JUST HEAR THE FIRST TALK IN THIS 7202 04:18:20,920 --> 04:18:23,000 SESSION AND THE PREVIOUS ONE AS 7203 04:18:23,000 --> 04:18:24,280 WELL AND AS WELL AS OTHER TALKS 7204 04:18:24,280 --> 04:18:25,960 YESTERDAY THAT ALREADY MENTIONED 7205 04:18:25,960 --> 04:18:27,160 MAPS SO YOU SHOULD BE FAMILIAR 7206 04:18:27,160 --> 04:18:29,000 WITH THAT AND SO I'M WORKING ON 7207 04:18:29,000 --> 04:18:32,440 THE TOOLS FOR THE CONSORTIUM AND 7208 04:18:32,440 --> 04:18:35,160 USES TO MAKE DATA VISUAL IN THE 7209 04:18:35,160 --> 04:18:38,200 PORTAL AND I'M PART OF THE THE 7210 04:18:38,200 --> 04:18:39,560 NETWORK AND DATA COORDINATION 7211 04:18:39,560 --> 04:18:45,840 CENTER AND ALSO PART OF THE SO I 7212 04:18:45,840 --> 04:18:47,040 HAVE DEALT WITH A LOT OF 7213 04:18:47,040 --> 04:18:48,800 CHALLENGES RELATED TO 7214 04:18:48,800 --> 04:18:51,280 VISUALIZATION OF REALLY WIDE 7215 04:18:51,280 --> 04:18:53,800 RANGE OF DATA TYPES AND ALSO 7216 04:18:53,800 --> 04:18:55,840 PARTICULARLY HAVE FOCUSED SORT 7217 04:18:55,840 --> 04:18:57,600 OF ON THIS ISSUE AND THIS 7218 04:18:57,600 --> 04:18:59,120 QUESTION OF HOW WE CAN BRING 7219 04:18:59,120 --> 04:19:00,200 DATA TOGETHER FROM DIFFERENT 7220 04:19:00,200 --> 04:19:01,600 DATA TYPES AND MAKE THAT 7221 04:19:01,600 --> 04:19:03,360 ACCESSIBLE TO THE COMMUNITY TO 7222 04:19:03,360 --> 04:19:05,760 VISUALIZATION IN A WAY THAT DOES 7223 04:19:05,760 --> 04:19:08,040 NOT REQUIRE ANYONE TO DOWNLOAD 7224 04:19:08,040 --> 04:19:09,680 SOFTWARE, DOWNLOAD DATA AND 7225 04:19:09,680 --> 04:19:13,360 INSTALL SOFTWARE AND LITTLELY 7226 04:19:13,360 --> 04:19:15,440 JUST TO A QUICK LOOK AT A 7227 04:19:15,440 --> 04:19:17,600 DATASET AND H AND E SLIDE OR 7228 04:19:17,600 --> 04:19:20,080 SOME MORE ADVANCED DATA TYPES 7229 04:19:20,080 --> 04:19:21,640 AND SO THIS IS SOMETHING THAT 7230 04:19:21,640 --> 04:19:24,840 I'VE REALLY WOULD LIKE TO SOLVE 7231 04:19:24,840 --> 04:19:26,680 ONE AND FOR ALL FOR THE 7232 04:19:26,680 --> 04:19:34,360 COMMUNITY AND THAT THE MAKE IT 7233 04:19:34,360 --> 04:19:44,920 DEFAULT AND EVEN JUST FOR A DATA 7234 04:19:45,200 --> 04:19:52,640 AND THERE ARE TOOLS HOW WE LOOK 7235 04:19:52,640 --> 04:19:55,320 AT GOOGLE MAPS, HOW WE'VE DONE 7236 04:19:55,320 --> 04:19:56,600 THAT FOR HUB MAP AND I'LL GIVE 7237 04:19:56,600 --> 04:19:58,000 YOU A COUPLE OF EXAMPLES OF THE 7238 04:19:58,000 --> 04:19:59,880 DATA THAT'S AVAILABLE AT HUB MAP 7239 04:19:59,880 --> 04:20:02,000 AND ALSO RELATED TO LYMPHATIC 7240 04:20:02,000 --> 04:20:03,160 TISSUE OF COURSE AND HOW YOU CAN 7241 04:20:03,160 --> 04:20:04,720 WORK WITH THAT AND HOW YOU CAN 7242 04:20:04,720 --> 04:20:07,320 ACCESS THAT AND HOW YOU CAN USE 7243 04:20:07,320 --> 04:20:07,800 OUR TOOLS. 7244 04:20:07,800 --> 04:20:10,880 IN OUR MAP, WE HAVE A LOT OF 7245 04:20:10,880 --> 04:20:13,800 DIFFERENT DATA TYPES AS YOU'VE 7246 04:20:13,800 --> 04:20:14,320 ALREADY HEARD. 7247 04:20:14,320 --> 04:20:16,840 THERE ARE MULTIPLE DIFFERENT 7248 04:20:16,840 --> 04:20:18,000 TECHNOLOGIES AND PROBABLY TWO OR 7249 04:20:18,000 --> 04:20:19,200 THROW DOZEN DIFFERENT 7250 04:20:19,200 --> 04:20:20,960 TECHNOLOGIES THAT ARE BEING USED 7251 04:20:20,960 --> 04:20:23,120 TO GENERATE SPECIAL DATA, SINGLE 7252 04:20:23,120 --> 04:20:24,920 CELL DATA, AND VARIOUS SCALES 7253 04:20:24,920 --> 04:20:27,720 BUT IT GOES DOWN TO SINGLE CELL 7254 04:20:27,720 --> 04:20:31,080 RESOLUTION, OF COURSE. 7255 04:20:31,080 --> 04:20:33,480 AND SO THAT POSED A CHALLENGE IN 7256 04:20:33,480 --> 04:20:36,520 TERMS OF DATA VISUALIZATION AND 7257 04:20:36,520 --> 04:20:38,760 WEB BASED DATA VISUALIZATION SO 7258 04:20:38,760 --> 04:20:41,240 YOU CAN JUST USE YOUR WEB 7259 04:20:41,240 --> 04:20:43,160 BROWSER AND SO WHAT HAVE YOU 7260 04:20:43,160 --> 04:20:44,360 DONE THERE? 7261 04:20:44,360 --> 04:20:47,080 IN HUBMAP, WHAT IS IMPORTANT TO 7262 04:20:47,080 --> 04:20:49,280 UNDERSTAND IS SO HOW HUBMAP 7263 04:20:49,280 --> 04:20:53,120 LOOKS AT THE WORLD OF LIKE THIS 7264 04:20:53,120 --> 04:20:55,160 CONCEPT OF CELL ATLAS AND THERE 7265 04:20:55,160 --> 04:21:05,680 ARE TWO PARTS TWO MAJOR PARTS TO 7266 04:21:12,000 --> 04:21:14,320 IT CONTAINS KNOWLEDGE 7267 04:21:14,320 --> 04:21:17,520 ABOUTORSANCE, TISSUE, CELL TYPES 7268 04:21:17,520 --> 04:21:19,040 AND STRUCTURES, FUNCTIONAL 7269 04:21:19,040 --> 04:21:29,600 TISSUE AND SO ON AND SO FOURTH. 7270 04:21:30,160 --> 04:21:36,720 CERTAIN DATA TYPES AND LIKE 7271 04:21:36,720 --> 04:21:40,240 EVERYONE WHICH ALLOWS YOU AND 7272 04:21:40,240 --> 04:21:41,440 OTHERS TO TAKE THESE DATASETS 7273 04:21:41,440 --> 04:21:43,520 AND RUN ANALYSIS KNOWING THAT 7274 04:21:43,520 --> 04:21:46,960 THE DATA HAS BEEN PRE PROCESSED 7275 04:21:46,960 --> 04:21:48,600 ACCORDINGLY AND THERE ARE FIRST 7276 04:21:48,600 --> 04:21:49,680 VISUALIZATIONS IN THE DATA 7277 04:21:49,680 --> 04:21:51,160 PORTAL AS WELL AND MANY, MANY 7278 04:21:51,160 --> 04:21:52,040 OTHER FEATURES. 7279 04:21:52,040 --> 04:21:54,280 I DON'T WANT TO GO INTO TOO MUCH 7280 04:21:54,280 --> 04:21:54,920 DETAIL MERE BECAUSE THIS DATA 7281 04:21:54,920 --> 04:21:57,760 POOL IS VERY COMPREHENSIVE AND I 7282 04:21:57,760 --> 04:21:58,880 DO WANT TO TELL YOU A LITTLE BIT 7283 04:21:58,880 --> 04:22:00,640 MORE ABOUT THE ATLAS THOUGH. 7284 04:22:00,640 --> 04:22:02,600 ON THE ATLAS SIDE, THERE'S A 7285 04:22:02,600 --> 04:22:06,080 COMMON COORDINATE FRAMEWORK USED 7286 04:22:06,080 --> 04:22:08,240 TO PUT DATASETS IN RELATION TO 7287 04:22:08,240 --> 04:22:11,600 EACH OTHER WITHIN THE HUMAN 7288 04:22:11,600 --> 04:22:11,880 BODY. 7289 04:22:11,880 --> 04:22:14,520 THIS COMMON FRAMEWORK IS USED TO 7290 04:22:14,520 --> 04:22:18,320 DESCRIBE REALLY HOW DATASETS AND 7291 04:22:18,320 --> 04:22:20,200 SAMPLES AND TISSUES THAT ARE 7292 04:22:20,200 --> 04:22:21,600 BEING STUDIED ARE PLACED IN THE 7293 04:22:21,600 --> 04:22:24,080 BODY AND HOW TO RELATE IT. 7294 04:22:24,080 --> 04:22:26,800 THERE'S IN DEED SOMETHING CALLED 7295 04:22:26,800 --> 04:22:28,000 A SPACIAL OR REGISTRATION USER 7296 04:22:28,000 --> 04:22:29,400 INTERFACE WHERE YOU CAN PLACE 7297 04:22:29,400 --> 04:22:31,440 DATA SUBMITTERS WOULD PLACE 7298 04:22:31,440 --> 04:22:33,320 TISSUE SAMPLES IN THE ORGANS 7299 04:22:33,320 --> 04:22:37,600 WHERE THEY WERE TAKING FROM SO 7300 04:22:37,600 --> 04:22:40,800 THAT SOMEONE PULLING IN THE 7301 04:22:40,800 --> 04:22:41,600 DATASETS THEY CAN FIGURE OUT 7302 04:22:41,600 --> 04:22:43,440 WHAT PART OF THE ORGAN WAS 7303 04:22:43,440 --> 04:22:44,880 STUDIED HERE AND SOMETHING IS 7304 04:22:44,880 --> 04:22:47,480 CALLED ACT PLUS B TABLES AND 7305 04:22:47,480 --> 04:22:49,880 CELL TIME AND BIOMARKER TABLES 7306 04:22:49,880 --> 04:22:53,080 THAT DESCRIBE WHICH KIND OF 7307 04:22:53,080 --> 04:22:55,360 BIOMARKERS ARE KNOWN TO DESCRIBE 7308 04:22:55,360 --> 04:22:58,760 CERTAIN TISSUES WITHIN AN ORGAN. 7309 04:22:58,760 --> 04:23:00,840 AND HOW CELL TYPES CAN BE 7310 04:23:00,840 --> 04:23:01,200 CHARACTERIZED. 7311 04:23:01,200 --> 04:23:02,600 AND, AGAIN, THERE'S A LOT MORE 7312 04:23:02,600 --> 04:23:04,280 TO THAT BUT THIS IS SORT OF JUST 7313 04:23:04,280 --> 04:23:07,320 A HIGH-LEVEL AND WE ARE ALSO 7314 04:23:07,320 --> 04:23:08,600 WORKING VERY ACTIVELY ON 7315 04:23:08,600 --> 04:23:09,920 BRINGING ALL OF THIS INFORMATION 7316 04:23:09,920 --> 04:23:11,360 TOGETHER AND SO THE DATA SHOULD 7317 04:23:11,360 --> 04:23:12,520 BE CONNECTED TO THE KNOWLEDGE SO 7318 04:23:12,520 --> 04:23:14,560 THAT THE DATA CAN BE USED SORT 7319 04:23:14,560 --> 04:23:16,600 OF AS SUPPORTING EVIDENCE FOR 7320 04:23:16,600 --> 04:23:18,240 KNOWLEDGE IN THE ATLAS BUT YOU 7321 04:23:18,240 --> 04:23:20,880 CAN NAVIGATE FROM THE ATLAS TO 7322 04:23:20,880 --> 04:23:21,840 DATASETS FOR EXAMPLE IF YOU ARE 7323 04:23:21,840 --> 04:23:22,880 INTERESTED IN A CERTAIN CELL 7324 04:23:22,880 --> 04:23:24,880 TYPES YOU CAN RETRIEVE DATASETS 7325 04:23:24,880 --> 04:23:26,840 OR PARTICULAR CELL TYPES OR OF A 7326 04:23:26,840 --> 04:23:30,120 CERTAIN TISSUE LIKE LYMPH NODE 7327 04:23:30,120 --> 04:23:30,920 OR SOMETHING LIKE THAT. 7328 04:23:30,920 --> 04:23:33,160 SO THIS COMBINED INTERPHASE WILL 7329 04:23:33,160 --> 04:23:34,960 ALLOW YOU TO ANSWER QUESTIONS ON 7330 04:23:34,960 --> 04:23:37,120 WHAT CELL TIMES ARE PRESENT AND 7331 04:23:37,120 --> 04:23:38,400 WHAT IS THE SPECIAL 7332 04:23:38,400 --> 04:23:40,600 ORGANIZATIONAL LOOK LIKE OF 7333 04:23:40,600 --> 04:23:41,440 CERTAIN TISSUES AND ALSO AGAIN 7334 04:23:41,440 --> 04:23:43,720 AS I SAID TO HAVE SUPPORTING 7335 04:23:43,720 --> 04:23:46,440 EVIDENCE UNDERLYING THE ATLAS 7336 04:23:46,440 --> 04:23:47,920 INFORMATION AND A MEASURE OF HOW 7337 04:23:47,920 --> 04:23:53,720 RELIABLE AND THE INFORMATION IS 7338 04:23:53,720 --> 04:24:00,480 THAT IS BEING AND I WANT TO TELL 7339 04:24:00,480 --> 04:24:02,040 YOU MORE ABOUT WHAT WE'RE DOING 7340 04:24:02,040 --> 04:24:05,360 THERE IN TERMS OF SUPPORTING 7341 04:24:05,360 --> 04:24:06,840 SCIENTISTS IN ANSWERING 7342 04:24:06,840 --> 04:24:09,640 QUESTIONS THAT THEY COME AND 7343 04:24:09,640 --> 04:24:14,200 BRING TO THE DATA PORT SO WE 7344 04:24:14,200 --> 04:24:15,360 WANT TO HELP DELIVER INSIDE AND 7345 04:24:15,360 --> 04:24:17,400 WE WANT TO MINIMIZE THE EFFORTS 7346 04:24:17,400 --> 04:24:19,120 AND NEEDS TO GO INTO GENERATING 7347 04:24:19,120 --> 04:24:20,520 THESE INSIGHTS. 7348 04:24:20,520 --> 04:24:23,760 AND SO, WE'RE DOING THIS 7349 04:24:23,760 --> 04:24:26,040 PRIMARILY THROUGH PROVIDING DATA 7350 04:24:26,040 --> 04:24:26,840 VISUALIZATION TOOLS THAT I'LL 7351 04:24:26,840 --> 04:24:29,400 TALK MORE ABOUT IN A MOMENT BUT 7352 04:24:29,400 --> 04:24:30,880 THEY'RE ALSO SOME FEATURES 7353 04:24:30,880 --> 04:24:32,400 COMING INTO THE DATA PORTAL AND 7354 04:24:32,400 --> 04:24:34,080 THEY'RE NOT RELEASED AND A TASTE 7355 04:24:34,080 --> 04:24:36,400 OF WHAT IS TO COME AND SO WE 7356 04:24:36,400 --> 04:24:40,400 HAVE TOOLS IN THE WORK THAT 7357 04:24:40,400 --> 04:24:46,480 ALLOWS YOU TO IN CERTAIN TYPES 7358 04:24:46,480 --> 04:24:48,480 AND WE'RE WORKING ON INGRA TIVE 7359 04:24:48,480 --> 04:24:49,760 DATA ANALYSIS TOOLS THAT WOULD 7360 04:24:49,760 --> 04:24:51,200 BE AVAILABLE DIRECTLY THROUGH 7361 04:24:51,200 --> 04:24:52,960 THE DATA PORTAL THAT YOU COULD 7362 04:24:52,960 --> 04:24:56,240 RUN IN THE WEB BROWSER. 7363 04:24:56,240 --> 04:24:59,760 THE MINIMIZE THE EFFORTS BY 7364 04:24:59,760 --> 04:25:01,160 BRINGING ALL THE TOOLS AND THE 7365 04:25:01,160 --> 04:25:03,320 DATA INTO THE WEB BROWSER TO 7366 04:25:03,320 --> 04:25:06,720 MAKE IT AS EASY AS POSSIBLE FOR 7367 04:25:06,720 --> 04:25:10,920 ANYONE TO START INTERACTING WITH 7368 04:25:10,920 --> 04:25:13,480 THE DATA. 7369 04:25:13,480 --> 04:25:17,240 THAT IS OUR MODEL TO MAXIMIZE BY 7370 04:25:17,240 --> 04:25:21,160 MINUTE MISSING THE NUMBERS OF 7371 04:25:21,160 --> 04:25:22,280 CLICKS THAT ARE REQUIRED TO TAKE 7372 04:25:22,280 --> 04:25:23,920 A ACTION. 7373 04:25:23,920 --> 04:25:25,680 SO, HERE ARE TOOLS TO DELIVERING 7374 04:25:25,680 --> 04:25:26,840 AND HERE ARE EXAMPLES THAT YOU 7375 04:25:26,840 --> 04:25:28,280 WILL SEE AND HOPEFULLY YOU CAN 7376 04:25:28,280 --> 04:25:29,480 SEE THE ANIMATIONS HERE. 7377 04:25:29,480 --> 04:25:30,920 THERE ARE MANY, MANY DIFFERENT 7378 04:25:30,920 --> 04:25:32,480 TYPES OF VISUALIZATIONS WE 7379 04:25:32,480 --> 04:25:34,200 SUPPORT AND ALL OF THEM USED THE 7380 04:25:34,200 --> 04:25:38,240 SAME VISUALIZATION FRAMEWORK 7381 04:25:38,240 --> 04:25:38,760 CALLED THE TEST. 7382 04:25:38,760 --> 04:25:40,160 WE HAVE SORT OF THESE 7383 04:25:40,160 --> 04:25:42,440 INTEGRATION TIVE MULTI MODAL 7384 04:25:42,440 --> 04:25:44,720 IMAGING DATASETS AND SUCH AS 7385 04:25:44,720 --> 04:25:46,720 THIS ONE AND THIS IS A DATASET 7386 04:25:46,720 --> 04:25:51,520 DONE ON LYMPH NODE. 7387 04:25:51,520 --> 04:25:53,360 WE HAVE A TISSUE VEER. 7388 04:25:53,360 --> 04:25:55,400 WE ARE CONTROL ANY CHANNEL 7389 04:25:55,400 --> 04:25:57,640 SETTINGS FOR THIS MULTI PLEX 7390 04:25:57,640 --> 04:26:00,440 DATASET AND WE CAN ALSO OVER LAY 7391 04:26:00,440 --> 04:26:03,400 THESE TISSUE SPICES WITH CELL 7392 04:26:03,400 --> 04:26:05,480 SEGMENTATIONS AND THEN SHOW 7393 04:26:05,480 --> 04:26:10,040 QUANTIFICATIONS FOR THESE 7394 04:26:10,040 --> 04:26:13,320 DIFFERENT CELL TYPES SO WE CAN 7395 04:26:13,320 --> 04:26:16,520 TURN IT OFF AND INTERACT WITH 7396 04:26:16,520 --> 04:26:16,720 THIS. 7397 04:26:16,720 --> 04:26:18,320 YOU SEE THE EMBEDDING AND THE 7398 04:26:18,320 --> 04:26:20,320 PLOT ON THE RIGHT THERE'S A HEAT 7399 04:26:20,320 --> 04:26:21,600 MAP VIEW WE CAN CHANGE WHICH 7400 04:26:21,600 --> 04:26:23,520 MARKERS WE WANT TO OVER LAYER 7401 04:26:23,520 --> 04:26:25,400 WHAT CLUSTERING OR CELL TYPE 7402 04:26:25,400 --> 04:26:26,480 ASSIGNMENTS WE WANT TO SHOW 7403 04:26:26,480 --> 04:26:27,760 HERE. 7404 04:26:27,760 --> 04:26:29,400 ALL OF THEE FEATURES ARE 7405 04:26:29,400 --> 04:26:37,640 AVAILABLE IN THE BROWSER AND 7406 04:26:37,640 --> 04:26:39,320 THIS THING LET'S ME MOVE ON AND 7407 04:26:39,320 --> 04:26:43,680 I WILL SHOW YOU ANOTHER EXAMPLE. 7408 04:26:43,680 --> 04:26:45,760 SO HERE IS ANOTHER EXAMPLE IS 7409 04:26:45,760 --> 04:26:49,960 THE 3D VIEW AND THIS IS ALSO 7410 04:26:49,960 --> 04:26:51,320 LYMPH NODE TISSUE IN THIS CASE. 7411 04:26:51,320 --> 04:26:55,880 SO WE HAVE A 3D VIEW AND WE HAVE 7412 04:26:55,880 --> 04:26:57,000 THE SAME FEATURES AND WE CAN 7413 04:26:57,000 --> 04:26:59,800 TURN ON AND OFF CERTAIN CHANNELS 7414 04:26:59,800 --> 04:27:02,720 AND ROTATE THE TISSUE AND CHANGE 7415 04:27:02,720 --> 04:27:05,440 THE SETTINGS AS WE WISH AND 7416 04:27:05,440 --> 04:27:07,440 AGAIN IT DOESN'T REQUIRE 7417 04:27:07,440 --> 04:27:09,280 ANYTHING FOR THE WEB BROWSER TO 7418 04:27:09,280 --> 04:27:11,320 DO THIS AND WE CAN DO THIS BY 7419 04:27:11,320 --> 04:27:12,680 PRE PROCESSING THE DATA IN 7420 04:27:12,680 --> 04:27:16,040 CERTAIN WAYS SO IT'S EASY TO DO 7421 04:27:16,040 --> 04:27:17,640 THAT ON THE FLY WITHOUT HAVING 7422 04:27:17,640 --> 04:27:20,480 TOO MUCH ON ENABLING THESE 7423 04:27:20,480 --> 04:27:22,600 VISUALIZATIONS SO IT'S A 7424 04:27:22,600 --> 04:27:23,560 STANDARDIZED PROCESS AND WE CAN 7425 04:27:23,560 --> 04:27:25,120 OPERATE ON ALL OF THESE 7426 04:27:25,120 --> 04:27:26,360 DIFFERENT DATA TYPES AND YOU SEE 7427 04:27:26,360 --> 04:27:33,800 THERE ARE OTHER EXAMPLE HERE 7428 04:27:33,800 --> 04:27:36,600 THIS IS THE SPACIAL TRANCE AND 7429 04:27:36,600 --> 04:27:38,840 WHERE YOU CAN SEE THIS PUCK ON 7430 04:27:38,840 --> 04:27:42,640 THE LEFT AND CENTER VIEW ON THE 7431 04:27:42,640 --> 04:27:44,240 RIGHT YOU HAVE THE SAME DATA AND 7432 04:27:44,240 --> 04:27:46,360 OVER LAY DIFFERENT CELL TYPES 7433 04:27:46,360 --> 04:27:48,480 THAT WERE DETECTED IN THIS 7434 04:27:48,480 --> 04:27:50,960 TISSUE USING THE STANDARDIZED 7435 04:27:50,960 --> 04:27:53,800 PIPELINES THAT WE HAVE IT ON 7436 04:27:53,800 --> 04:27:54,160 MAP. 7437 04:27:54,160 --> 04:27:58,600 SO ALL OF THAT IS AVAILABLE TO 7438 04:27:58,600 --> 04:28:02,240 USERS OFF THE HUBMAP DATA 7439 04:28:02,240 --> 04:28:02,480 PORTAL. 7440 04:28:02,480 --> 04:28:03,760 THIS IS DONE THROUGH THE 7441 04:28:03,760 --> 04:28:05,800 FRAMEWORK CALLED THE TEST THAT 7442 04:28:05,800 --> 04:28:08,000 ANYONE CAN USE THAT IS OPEN 7443 04:28:08,000 --> 04:28:08,640 SOURCE SOFTWARE AND THERE'S A 7444 04:28:08,640 --> 04:28:10,000 LOT OF DOCUMENTATION AND 7445 04:28:10,000 --> 04:28:11,080 EXAMPLES AVAILABLE AND HOW YOU 7446 04:28:11,080 --> 04:28:13,080 CAN SET UP YOUR OWN 7447 04:28:13,080 --> 04:28:14,280 VISUALIZATIONS WITH THIS 7448 04:28:14,280 --> 04:28:14,560 FRAMEWORK. 7449 04:28:14,560 --> 04:28:15,840 AND WHAT WE'RE DOING RIGHT NOW, 7450 04:28:15,840 --> 04:28:17,640 THIS IS ONLY SORT OF AT THE 7451 04:28:17,640 --> 04:28:19,800 SINGLE DATASET LEVEL. 7452 04:28:19,800 --> 04:28:22,440 EVEN THOUGH THEY'RE HIGHLY 7453 04:28:22,440 --> 04:28:24,680 INTEGRATION TIVE, VISUALIZATIONS 7454 04:28:24,680 --> 04:28:29,360 AND WE CAN SUPPORT MULTI OMIC 7455 04:28:29,360 --> 04:28:30,880 SETS AS WELL, THOSE ARE ALL FOR 7456 04:28:30,880 --> 04:28:31,640 ONE SINGLE CELL. 7457 04:28:31,640 --> 04:28:34,280 THE SINGLE DATASET VISUALIZATION 7458 04:28:34,280 --> 04:28:35,800 THAT WE'RE SUPPORTING RIGHT 7459 04:28:35,800 --> 04:28:38,560 THOUSAND BUT WE CAN BRING IN 7460 04:28:38,560 --> 04:28:40,320 CLUSTERING RESULTS, 7461 04:28:40,320 --> 04:28:42,600 SEGMENTATION, CELL TYPE A 7462 04:28:42,600 --> 04:28:45,000 SENMENTS AND IT HELPS INTERPRET 7463 04:28:45,000 --> 04:28:45,520 THE DATA. 7464 04:28:45,520 --> 04:28:47,480 WHAT WE DO DO RIGHT NOW AND WHAT 7465 04:28:47,480 --> 04:28:49,680 WE WILL DO IN THE FUTURE IS 7466 04:28:49,680 --> 04:28:50,640 VISUALIZATION OF MULTIPLE 7467 04:28:50,640 --> 04:28:54,280 DATASETS SO YOU CAN LOOK ACROSS 7468 04:28:54,280 --> 04:28:56,040 CELL TYPE ABUNDANCE FOR TISSUE 7469 04:28:56,040 --> 04:28:57,680 RATHER THAN JUST LOOKING AT ONE 7470 04:28:57,680 --> 04:28:58,920 DATASET AT A TIME AND IN THE 7471 04:28:58,920 --> 04:29:01,280 FUTURE WE'LL SUPPORT A HIGH 7472 04:29:01,280 --> 04:29:04,520 LEVEL VISUALIZATION OF THE WHOLE 7473 04:29:04,520 --> 04:29:04,920 ATLAS. 7474 04:29:04,920 --> 04:29:06,320 OTHER FEATURES THAT I WANT TO 7475 04:29:06,320 --> 04:29:07,840 MENTION VERY BRIEFLY THAT CAN BE 7476 04:29:07,840 --> 04:29:10,400 USEFUL WHEN IT'S RELEASED IS 7477 04:29:10,400 --> 04:29:12,000 THIS CROSS DATASETS SO HERE IS 7478 04:29:12,000 --> 04:29:17,240 AN EXAMPLE WHERE WE CAN 7479 04:29:17,240 --> 04:29:18,360 BIOMARKERS SO IN THIS CASE YOU 7480 04:29:18,360 --> 04:29:20,720 SELECT A GENE BIOMARKER AND IN 7481 04:29:20,720 --> 04:29:24,920 THIS CASE WE'RE INTERESTED IN 7482 04:29:24,920 --> 04:29:26,000 RNA AND QUANTIFICATIONS AND 7483 04:29:26,000 --> 04:29:27,560 DETERMINE SORT OF SOME CUT-OFFS 7484 04:29:27,560 --> 04:29:29,200 FOR WHAT SHOULD BE THE LEVEL OF 7485 04:29:29,200 --> 04:29:31,320 EXPRESSION FOR THIS MARKER. 7486 04:29:31,320 --> 04:29:32,280 AND HOW MANY -- WHAT PERCENTAGE 7487 04:29:32,280 --> 04:29:34,200 OF CELLS IN A GIVEN DATASET 7488 04:29:34,200 --> 04:29:35,520 SHOULD THIS MARKER BE PRESENT 7489 04:29:35,520 --> 04:29:40,960 AND WE CAN RUN A QUERY AND WE 7490 04:29:40,960 --> 04:29:42,440 CAN SORT OF START DRILLING INTO 7491 04:29:42,440 --> 04:29:44,520 THAT AND VISUALIZING THE 7492 04:29:44,520 --> 04:29:46,160 EXPRESSION PROFILE OFF THAT 7493 04:29:46,160 --> 04:29:47,600 MARKER ACROSS THE CLUSTERS OR 7494 04:29:47,600 --> 04:29:50,160 CELL TYPES IN THAT TISSUE. 7495 04:29:50,160 --> 04:29:52,520 AND SO WE CAN THEN NAVIGATE 7496 04:29:52,520 --> 04:29:54,520 DIRECTLY TO THE DATASETS HERE 7497 04:29:54,520 --> 04:29:57,560 IT'S ANOTHER KIDNEY DATASET. 7498 04:29:57,560 --> 04:29:58,800 WE CAN THEN DO THE SAME THING 7499 04:29:58,800 --> 04:30:04,240 AND WE CAN LOOK AT THE 7500 04:30:04,240 --> 04:30:06,280 EXPRESSION MARKER SO IT'S A 7501 04:30:06,280 --> 04:30:07,920 QUICK WAY OF FINDING A DATASET 7502 04:30:07,920 --> 04:30:12,280 WITH A MARKER OF INTEREST. 7503 04:30:12,280 --> 04:30:15,920 AND I'M JUST TRYING TO -- IT'S 7504 04:30:15,920 --> 04:30:17,320 VERY INTERACTIVE AND YOU CAN 7505 04:30:17,320 --> 04:30:18,520 PLAY AROUND WITH THE DATA. 7506 04:30:18,520 --> 04:30:19,640 AGAIN, WITHOUT ANYTHING, IT'S 7507 04:30:19,640 --> 04:30:21,600 JUST A COUPLE OF CLICKS TO GET 7508 04:30:21,600 --> 04:30:23,200 TO THESE KIND OF FEATURES. 7509 04:30:23,200 --> 04:30:24,760 IN THE FUTURE, WE WILL ALSO WANT 7510 04:30:24,760 --> 04:30:27,480 TO PROVIDE SUPPORT FOR 7511 04:30:27,480 --> 04:30:29,520 COMPUTATIONAL ANNALISTS AND 7512 04:30:29,520 --> 04:30:31,400 BIOLOGISTS AND OTHER PEOPLE WHO 7513 04:30:31,400 --> 04:30:37,480 WRITE SCRIPTS TO ANALYZE DATA TO 7514 04:30:37,480 --> 04:30:39,320 RUN CODE DIRECTLY BY USING WHAT 7515 04:30:39,320 --> 04:30:41,520 THOSE OF YOU WHO ARE FAMILIAR 7516 04:30:41,520 --> 04:30:44,040 WITH THAT, JUPYTER NOTEBOOKS AND 7517 04:30:44,040 --> 04:30:46,560 THAT CAN REALLY ALLOW YOU TO NOT 7518 04:30:46,560 --> 04:30:48,560 ONLY USE THE STANDARD FEATURES 7519 04:30:48,560 --> 04:30:50,960 BUILT INTO THE HUB MAP PORTAL 7520 04:30:50,960 --> 04:30:54,200 INTERFACE AND RUN YOUR OWN 7521 04:30:54,200 --> 04:30:56,160 ALGORITHMS SO YOU CAN RUN A 7522 04:30:56,160 --> 04:30:58,160 QUERY, FOR EXAMPLE AND YOU CAN 7523 04:30:58,160 --> 04:31:00,040 QUERY THE METADATA OF THE 7524 04:31:00,040 --> 04:31:01,720 DATASETS AND CREATE YOUR 7525 04:31:01,720 --> 04:31:05,560 VISUALIZATIONS ON THE FLY AND 7526 04:31:05,560 --> 04:31:06,240 DOWNLOAD NOTEBOOKS THAT CONTAINS 7527 04:31:06,240 --> 04:31:08,200 A SAMPLE CODE TO ALLOW YOU TO 7528 04:31:08,200 --> 04:31:10,200 RUN ANALYSIS AND WE CAN DOWNLOAD 7529 04:31:10,200 --> 04:31:11,840 THESE VISUALIZATIONS WHICH CAN 7530 04:31:11,840 --> 04:31:14,000 ALSO BE EMBEDDED DIRECTLY INTO 7531 04:31:14,000 --> 04:31:14,760 JUPYTER NOTEBOOKS. 7532 04:31:14,760 --> 04:31:16,520 FUR A COMPUTATIONAL ANNALIST AND 7533 04:31:16,520 --> 04:31:19,560 YOU WONDER HOW TO ANALYZE YOUR 7534 04:31:19,560 --> 04:31:21,200 SINGLE CELL DATA WITH A TOOL CAN 7535 04:31:21,200 --> 04:31:28,280 YOU DO THIS AND THIS IS AN 7536 04:31:28,280 --> 04:31:30,880 EXAMPLE INTO THE JUPITER 7537 04:31:30,880 --> 04:31:33,360 NOTEBOOK AND LAUNCH IT OR THE 7538 04:31:33,360 --> 04:31:34,640 VISUALIZATION IN THE NOTEBOOK 7539 04:31:34,640 --> 04:31:36,560 AND INTERACT WITH T I'M RUNNING 7540 04:31:36,560 --> 04:31:37,520 OUT OF TIME SO I WANT TO TRY TO 7541 04:31:37,520 --> 04:31:39,280 WRAP THIS UP. 7542 04:31:39,280 --> 04:31:40,800 THESE FEATURES WILL BE AVAILABLE 7543 04:31:40,800 --> 04:31:43,400 DIRECTLY IN THE PORTAL WHERE YOU 7544 04:31:43,400 --> 04:31:45,520 CAN RUN AN EX CUTE THE NOTEBOOKS 7545 04:31:45,520 --> 04:31:47,960 WITHOUT EVEN DOWNLOADING THEM 7546 04:31:47,960 --> 04:31:48,920 EVENTUALLY, THAT'S COMING UP 7547 04:31:48,920 --> 04:31:49,280 SOON. 7548 04:31:49,280 --> 04:31:53,280 WE'RE CLOSE TO RELEASING THIS 7549 04:31:53,280 --> 04:31:54,560 FEWTURE AND THIS IS BUILT INTO 7550 04:31:54,560 --> 04:31:56,760 THE HUB MAP PORTAL FOR THIS 7551 04:31:56,760 --> 04:31:57,160 PURPOSE. 7552 04:31:57,160 --> 04:31:58,720 I'VE TALKED ABOUT THIS AND I DO 7553 04:31:58,720 --> 04:32:05,560 WANT TO POINT OUT YOU KNOW, WE 7554 04:32:05,560 --> 04:32:16,080 HAVE ON THE HOME PAGE, THE DATA 7555 04:32:17,560 --> 04:32:18,800 TYPES WE HAVE AVAILABLE AND 7556 04:32:18,800 --> 04:32:21,160 THERE'S QUITE A BIT OF LYMPHATIC 7557 04:32:21,160 --> 04:32:23,440 TISSUE AVAILABLE AND THE DON'T 7558 04:32:23,440 --> 04:32:25,040 FROM LYMPHATIC TISSUES THAT YOU 7559 04:32:25,040 --> 04:32:34,240 CAN ACT AS A SINGLE CELL IMAGINF 7560 04:32:34,240 --> 04:32:35,560 THOUGHTS ON CHALLENGES IN THESE 7561 04:32:35,560 --> 04:32:35,880 SPACE. 7562 04:32:35,880 --> 04:32:36,960 THESE ARE DIFFERENT FROM WHAT 7563 04:32:36,960 --> 04:32:38,000 OTHER PEOPLE HAVE MENTIONED. 7564 04:32:38,000 --> 04:32:40,720 TO ME, THE CHALLENGES FALL INTO 7565 04:32:40,720 --> 04:32:42,160 THREE CATEGORIES. 7566 04:32:42,160 --> 04:32:44,840 SOCIOLOGICAL RELATED TO HOW 7567 04:32:44,840 --> 04:32:49,880 USERS DO RESEARCH AND HOW WE 7568 04:32:49,880 --> 04:32:51,040 ESSENTIALLY TRY TO LEARN FROM 7569 04:32:51,040 --> 04:32:53,040 OUR USERS WHAT KIND OF FEATURES 7570 04:32:53,040 --> 04:32:54,560 THEY NEED IN THOSE VISUALIZATION 7571 04:32:54,560 --> 04:32:56,040 TOOLS SO IT'S ONE CHALLENGE FOR 7572 04:32:56,040 --> 04:32:56,200 US. 7573 04:32:56,200 --> 04:32:58,880 WE NEED TO DO USER RESEARCH AND 7574 04:32:58,880 --> 04:33:00,760 SINCE EVERY SCIENTIST HAS THEIR 7575 04:33:00,760 --> 04:33:02,160 OWN PROBLEM AND NICHE THEY'RE 7576 04:33:02,160 --> 04:33:04,760 TRYING TO SOLVE, MEDICINE IS 7577 04:33:04,760 --> 04:33:05,720 CHALLENGING BECAUSE WE NEED TO 7578 04:33:05,720 --> 04:33:06,920 TALK TO A LOT OF PEOPLE TO 7579 04:33:06,920 --> 04:33:08,880 FIGURE OUT WHAT IS FUNCTIONALITY 7580 04:33:08,880 --> 04:33:10,800 FOR THESE VISUALIZATION TOOLS. 7581 04:33:10,800 --> 04:33:12,560 THERE ARE CHALLENGES RELATED TO 7582 04:33:12,560 --> 04:33:14,840 NECK KNOWLEDGES AND DATA FORMAT 7583 04:33:14,840 --> 04:33:16,000 AND EVERYONE WILL BE FAMILIAR 7584 04:33:16,000 --> 04:33:17,880 WITH THOSE AND MAYBE FOR PEOPLE 7585 04:33:17,880 --> 04:33:19,400 WHO ARE WORKING WITH IMAGING 7586 04:33:19,400 --> 04:33:21,240 DATA IT'S BEEN SOLVED AND FOR 7587 04:33:21,240 --> 04:33:23,360 MOST OF THE OTHER DATA 7588 04:33:23,360 --> 04:33:25,160 MORTALITIES THIS IS STILL AN 7589 04:33:25,160 --> 04:33:26,560 OPEN QUESTION OF THE STANDARD 7590 04:33:26,560 --> 04:33:30,720 FORMATS AND HU T HOW THEY WORK. 7591 04:33:30,720 --> 04:33:31,920 SCIENTISTS TRY TO ANSWER UNIQUE 7592 04:33:31,920 --> 04:33:34,520 QUESTIONS AND IT MAKES IT HARD 7593 04:33:34,520 --> 04:33:35,760 TO BUILD GENERALIZED TOOLS THAT 7594 04:33:35,760 --> 04:33:36,480 WORK FOR EVERYONE. 7595 04:33:36,480 --> 04:33:38,160 THERE ARE GREAT OPPORTUNITIES 7596 04:33:38,160 --> 04:33:41,000 AND I THINK THERE'S ALREADY ON 7597 04:33:41,000 --> 04:33:43,200 GOING EFFORTS FOR PEOPLE LIKE ME 7598 04:33:43,200 --> 04:33:45,120 AND OTHER COMPUTATIONAL FOLKS TO 7599 04:33:45,120 --> 04:33:46,560 WORK TOGETHER ON IDENTIFYING 7600 04:33:46,560 --> 04:33:50,640 COMMON CHALLENGES ACROSS THESE 7601 04:33:50,640 --> 04:33:53,120 EFFORTS AND BUILD SOLUTIONS FOR 7602 04:33:53,120 --> 04:33:55,000 THAT AND I THINK THIS COMMUNITY 7603 04:33:55,000 --> 04:33:57,240 WILL ALSO BE ABLE TO BENEFIT OF 7604 04:33:57,240 --> 04:33:59,520 COURSE FROM BEST PRACTICES THAT 7605 04:33:59,520 --> 04:34:01,440 PROJECTS LIKE HUBMAP OR HUMAN 7606 04:34:01,440 --> 04:34:03,800 CELL ATLAS HAVE DEVELOPED AND 7607 04:34:03,800 --> 04:34:05,280 COME UP WITH THE PAST AND IF YOU 7608 04:34:05,280 --> 04:34:06,760 WANT TO PARTICIPATE IN THAT, I 7609 04:34:06,760 --> 04:34:08,080 CERTAINLY HAVE A NUMBER OF OPEN 7610 04:34:08,080 --> 04:34:09,960 POSITIONS IN MY LAB FOR ANYONE 7611 04:34:09,960 --> 04:34:12,440 WHO IS LOOKING FOR NEXT STEP IN 7612 04:34:12,440 --> 04:34:13,200 THEIR CAREER. 7613 04:34:13,200 --> 04:34:14,600 THANK YOU VERY MUCH. 7614 04:34:14,600 --> 04:34:17,160 APOLOGIES FOR GOING OVER TIME. 7615 04:34:17,160 --> 04:34:19,440 >> THANK YOU SO MUCH, NILS. 7616 04:34:19,440 --> 04:34:20,440 YEAH, WE'LL HOLD OUR QUESTIONS 7617 04:34:20,440 --> 04:34:22,240 TO THE END BUT I'M GRATEFUL FOR 7618 04:34:22,240 --> 04:34:24,200 THE LOVE LETTER FOR HUBMAP AND 7619 04:34:24,200 --> 04:34:24,800 DATA SCIENCE. 7620 04:34:24,800 --> 04:34:27,440 OUR LAST AND FINAL SPEAK OF THE 7621 04:34:27,440 --> 04:34:29,680 SYMPOSIUM IS Dr. HELEN 7622 04:34:29,680 --> 04:34:30,760 BENVENISTE. 7623 04:34:30,760 --> 04:34:32,760 SO, COME ON DOWN, YOU CAN GET 7624 04:34:32,760 --> 04:34:34,320 YOUR SLIDES CUED UP. 7625 04:34:34,320 --> 04:34:40,120 SHE'S A PROFESSOR OF 7626 04:34:40,120 --> 04:34:40,760 ANESTHESIOLOGY AT YALE AND 7627 04:34:40,760 --> 04:34:42,840 INCLUDING THE DEVELOPMENT OF 7628 04:34:42,840 --> 04:34:44,880 METHODOLOGIES TO EXAM THE WASTE 7629 04:34:44,880 --> 04:34:46,040 REMOVE PROCESS IN THE BRAIN. 7630 04:34:46,040 --> 04:34:50,760 THE TITLE IS 3D IMAGING FLUID 7631 04:34:50,760 --> 04:34:51,920 AND WASTE CLEARING FROM BRAIN 7632 04:34:51,920 --> 04:34:53,840 AND EXPERIMENTAL MODELS OF 7633 04:34:53,840 --> 04:34:54,920 IMPAIRED LYMPHATIC SYSTEM. 7634 04:34:54,920 --> 04:34:57,520 THANK YOU AND WELCOME. 7635 04:34:57,520 --> 04:34:59,480 >> HELLO AND THANK YOU FOR IN 7636 04:34:59,480 --> 04:35:02,520 INVITING ME TO THIS INTRIGUING 7637 04:35:02,520 --> 04:35:04,120 WORKSHOP AND I ALSO WANT TO 7638 04:35:04,120 --> 04:35:07,520 CONFESS THAT I'M A NEWCOMER TO 7639 04:35:07,520 --> 04:35:10,960 THE FIELD OF THE LYMPHATICS BUT 7640 04:35:10,960 --> 04:35:11,720 I'VE BEEN DARING MYSELF TO KEEP 7641 04:35:11,720 --> 04:35:14,400 OPEN THE BARRIER AND THIS IS 7642 04:35:14,400 --> 04:35:16,240 SOME OF THE DATA I WILL BE 7643 04:35:16,240 --> 04:35:17,040 TALKING TO YOU ABOUT TODAY. 7644 04:35:17,040 --> 04:35:19,200 I WANT TO ACKNOWLEDGE SUPPORT 7645 04:35:19,200 --> 04:35:21,640 FROM THE NIH, THE BRAIN ENTRY 7646 04:35:21,640 --> 04:35:23,800 EXIST CONSORTIUM AND SUPPORTED 7647 04:35:23,800 --> 04:35:27,840 BY THE ALZHEIMER'S FOUNDATION 7648 04:35:27,840 --> 04:35:30,240 AND ALSO (INAUDIBLE) FOUNDATION. 7649 04:35:30,240 --> 04:35:32,480 THERE'S A LOT OF NEW KNOWLEDGE 7650 04:35:32,480 --> 04:35:34,360 OF HOW THE BRAIN AND FLUID AND 7651 04:35:34,360 --> 04:35:36,280 CONNECT TO THE LYMPHATIC SYSTEM 7652 04:35:36,280 --> 04:35:39,000 HAVE EMERGED AND MAPS OF THE 7653 04:35:39,000 --> 04:35:40,640 LYMPHATICS AND THE DRAINAGE 7654 04:35:40,640 --> 04:35:44,040 PATHWAYS TO THE CERVICAL LYMPH 7655 04:35:44,040 --> 04:35:45,640 NODES ARE BASED ON DATA FROM 7656 04:35:45,640 --> 04:35:48,760 RODENTS AS WELL AS FROM HUMAN 7657 04:35:48,760 --> 04:35:50,680 BRAIN AND I WANT TO HIGHLIGHT 7658 04:35:50,680 --> 04:35:54,600 THE WORK OF THE DOCTORS' LAB 7659 04:35:54,600 --> 04:35:56,280 THEIR WORK HAS REALLY BEEN 7660 04:35:56,280 --> 04:35:57,960 INSTRUMENTAL FOR PROVIDING US 7661 04:35:57,960 --> 04:36:00,440 THIS NEW UNDERSTANDING OF THE 7662 04:36:00,440 --> 04:36:02,360 DRAINAGE PATHWAY ROUTES FROM THE 7663 04:36:02,360 --> 04:36:03,160 BRAIN. 7664 04:36:03,160 --> 04:36:05,560 HOWEVER, THESE PATHWAYS HAVE TO 7665 04:36:05,560 --> 04:36:08,240 BE UNDERSTOOD AND DISCUSSED IN 7666 04:36:08,240 --> 04:36:10,640 CONNECTION WITH THE BRAIN'S 7667 04:36:10,640 --> 04:36:13,760 WASTE DISPOSAL SYSTEM. 7668 04:36:13,760 --> 04:36:15,840 THIS IS A SCHEMATIC PRESENTATION 7669 04:36:15,840 --> 04:36:19,000 OF WHAT WE CALL THE LYMPHATIC 7670 04:36:19,000 --> 04:36:20,560 MODEL OF WASTE CLEARANCE WHICH 7671 04:36:20,560 --> 04:36:24,080 WAS INTRODUCED ABOUT A DECADE 7672 04:36:24,080 --> 04:36:24,640 AGO BY. 7673 04:36:24,640 --> 04:36:28,000 I WANT TO HIGHLIGHT THE KEY 7674 04:36:28,000 --> 04:36:30,120 FEATURES OF THIS MODEL WHICH 7675 04:36:30,120 --> 04:36:33,240 INCLUDES INWORK FLOW OF FLUID 7676 04:36:33,240 --> 04:36:35,000 ALONG THE SPACE IS OF THE 7677 04:36:35,000 --> 04:36:39,040 PENETRATING AR TERRIER OF THE 7678 04:36:39,040 --> 04:36:40,880 BRAIN AND THE SPACE IS MADE UP 7679 04:36:40,880 --> 04:36:44,240 BY THE INNEED OF THE GLEE OWE 7680 04:36:44,240 --> 04:36:46,120 CELLS AND THAT WATER CHANNELS 7681 04:36:46,120 --> 04:36:48,840 ARE DECORATING THESE AND THEY 7682 04:36:48,840 --> 04:36:51,320 ARE IMPLICATED IN THE TRANSFER 7683 04:36:51,320 --> 04:36:54,640 OF FLUID FROM THIS SPACE AND 7684 04:36:54,640 --> 04:36:57,480 INTO THE FLUID AND THIS IS 7685 04:36:57,480 --> 04:37:00,560 PROVEN BY BLOOD FLOW AND THIS IS 7686 04:37:00,560 --> 04:37:02,680 MEANT BY TO SERVE AS A DRIVER 7687 04:37:02,680 --> 04:37:06,680 FOR HOW THE FLUID AND THE WASTE 7688 04:37:06,680 --> 04:37:09,520 HERE INTO THE SPACES AND HOW TO 7689 04:37:09,520 --> 04:37:11,080 THE LYMPHATICS. 7690 04:37:11,080 --> 04:37:13,000 AND I JUST WANT TO HIGHLIGHT 7691 04:37:13,000 --> 04:37:16,440 THAT THIS SYSTEM IS SO UNIQUE 7692 04:37:16,440 --> 04:37:22,080 AND THE TEAM HAVE DISCOVERED 7693 04:37:22,080 --> 04:37:24,480 THIS TEAM IS POLICE STATIONAL 7694 04:37:24,480 --> 04:37:30,160 ACTIVE DURING DEEPSLEEP. 7695 04:37:30,160 --> 04:37:32,320 THIS IS REALLY UNIQUE AND I 7696 04:37:32,320 --> 04:37:38,960 WON'T HAVE TIME TO TALK ABOUT 7697 04:37:38,960 --> 04:37:43,440 THIS, HOWEVER, I WANT TO POINT 7698 04:37:43,440 --> 04:37:45,360 OUT THIS IS NOT THE ONLY MODEL 7699 04:37:45,360 --> 04:37:55,040 FOR WASTE CLEARANCE AND THIS IS 7700 04:37:55,040 --> 04:38:00,520 A MODEL I HIGHLIGHTED AND THE 7701 04:38:00,520 --> 04:38:02,240 OUTFLOW AND THERE ARE OTHER 7702 04:38:02,240 --> 04:38:03,560 MODELS AND YOU WANT TO HIGHLIGHT 7703 04:38:03,560 --> 04:38:05,280 THE MIXING MODEL WHICH IS I 7704 04:38:05,280 --> 04:38:07,280 THINK IS ALSO REALLY LOOKED AT 7705 04:38:07,280 --> 04:38:09,840 WHERE THEY ARE CLAIMING THAT 7706 04:38:09,840 --> 04:38:13,240 THERE'S NO IN THE BRAIN AND THIS 7707 04:38:13,240 --> 04:38:16,120 IS ALSO MOVEMENT AND EVERYTHING 7708 04:38:16,120 --> 04:38:17,480 IS WASTE SOLIDS ARE ACTUALLY 7709 04:38:17,480 --> 04:38:21,680 MOVING OUST OF THE BRAIN BY 7710 04:38:21,680 --> 04:38:22,960 DIFFUSION ONLY AND THE ONLY 7711 04:38:22,960 --> 04:38:25,760 BLOOD FLOW WE HAVE IS ON THE 7712 04:38:25,760 --> 04:38:27,920 SURFACE AND INTO THE SURVIVE 7713 04:38:27,920 --> 04:38:28,400 SPACE. 7714 04:38:28,400 --> 04:38:31,000 HOWEVER, BASED ON THE NEW 7715 04:38:31,000 --> 04:38:32,000 LITERATURE, I WOULD SAY THE 7716 04:38:32,000 --> 04:38:34,160 LYMPHATIC AND MIXING MODEL ARE 7717 04:38:34,160 --> 04:38:35,760 PROBABLY THE BETTER ONCE ALIGNED 7718 04:38:35,760 --> 04:38:37,760 WITH THE BIOLOGY AND SHOW HERE 7719 04:38:37,760 --> 04:38:42,600 IS THE MOST RECENT SCHEMATIC MAP 7720 04:38:42,600 --> 04:38:43,840 OF THE DUEL VINO LYMPHATIC 7721 04:38:43,840 --> 04:38:46,840 NETWORK AS DEPICTED IN THE MOUSE 7722 04:38:46,840 --> 04:38:48,960 BRAIN AND YOU CAN SEE THE DUEL 7723 04:38:48,960 --> 04:38:51,200 SINUS AND DECORATED WITH A 7724 04:38:51,200 --> 04:38:52,200 LYMPHATIC HERE AND THESE NUMBERS 7725 04:38:52,200 --> 04:38:55,960 HERE ON THE SURFACE HAVE SHOWN 7726 04:38:55,960 --> 04:38:59,640 EXACTLY WHERE THE MENINGEAL 7727 04:38:59,640 --> 04:39:02,720 LYMPHATIC SITES AND ARE 7728 04:39:02,720 --> 04:39:04,040 RECEIVING THE LYMPHATIC AND 7729 04:39:04,040 --> 04:39:07,120 OUTPUT AND I RECOMMEND YOU TO 7730 04:39:07,120 --> 04:39:11,400 READ THE POPULAR -- IT'S A 7731 04:39:11,400 --> 04:39:12,160 REALLY BEAUTIFUL PAPER. 7732 04:39:12,160 --> 04:39:13,800 I MEAN, YOU KNOW, THESE THINGS 7733 04:39:13,800 --> 04:39:15,760 HAVE STILL DEBATED BUT I THINK 7734 04:39:15,760 --> 04:39:19,200 THIS PAPER HAS REALLY 7735 04:39:19,200 --> 04:39:20,360 HIGHLIGHTED SOME KEY CONCEPTS 7736 04:39:20,360 --> 04:39:22,000 AND THIS IS WHAT WE WANT TO 7737 04:39:22,000 --> 04:39:23,760 IMAGE, SO IF THE LYMPHATIC 7738 04:39:23,760 --> 04:39:26,360 SYSTEM IS A VARIABLE AND 7739 04:39:26,360 --> 04:39:28,280 ACCESSIBLE, THE SPINAL FLUID HAS 7740 04:39:28,280 --> 04:39:30,840 TO INTERCHANGE WITH INTER TISSUE 7741 04:39:30,840 --> 04:39:33,760 FLUID TO TRANSPORT THE SOLUTE SO 7742 04:39:33,760 --> 04:39:35,560 WE CAN CALL THIS DIRTY CSF AND 7743 04:39:35,560 --> 04:39:38,160 IT'S HIGHLIGHTED IN THESE PAPERS 7744 04:39:38,160 --> 04:39:40,240 AND WE THINK THAT THAT DIRTY CSF 7745 04:39:40,240 --> 04:39:41,600 THAT HAS PASSED THROUGH THE 7746 04:39:41,600 --> 04:39:43,920 LYMPHATICS IS ACTUALLY CONNECTED 7747 04:39:43,920 --> 04:39:51,000 TO THE MIN WHEN THIS SYSTEM IS T 7748 04:39:51,000 --> 04:39:53,600 AVAILABLE, THE CSF IS 7749 04:39:53,600 --> 04:39:58,640 CIRCULATING BUT IT'S NOT GOING 7750 04:39:58,640 --> 04:39:59,920 INTO THE EGRESSING FROM OTHER 7751 04:39:59,920 --> 04:40:05,760 ROUTES, PROBABLY VIA THE CRANIAL 7752 04:40:05,760 --> 04:40:06,120 NERVES. 7753 04:40:06,120 --> 04:40:08,000 FOR ABOUT A DECADE, WE 7754 04:40:08,000 --> 04:40:09,920 INTRODUCED A WAY TO TRACK 7755 04:40:09,920 --> 04:40:14,880 LYMPHATIC TRANSPORT IN THE TRAI. 7756 04:40:14,880 --> 04:40:17,480 THERE'S A LOT OF OTHER OUT THERE 7757 04:40:17,480 --> 04:40:19,160 AND THIS IS THE ONE I'M GOING TO 7758 04:40:19,160 --> 04:40:21,280 FOCUS ON TODAY. 7759 04:40:21,280 --> 04:40:23,040 I USE RATS IN THE LAB BECAUSE 7760 04:40:23,040 --> 04:40:24,960 THEY'RE BIGGER THAN MICE AND WE 7761 04:40:24,960 --> 04:40:26,800 CAN ALSO DO THIS IN MICE BUT WE 7762 04:40:26,800 --> 04:40:28,760 HAD REALLY WORKED A LOT IN THE 7763 04:40:28,760 --> 04:40:32,520 RAT AND WE INJECT SMALL 7764 04:40:32,520 --> 04:40:34,160 MOLECULAR AND AGENTS INTO THE 7765 04:40:34,160 --> 04:40:38,560 CSF VIA THE AND THEN YOU CAN SEE 7766 04:40:38,560 --> 04:40:41,360 HERE WE CAN MAP DYNAMICALLY 7767 04:40:41,360 --> 04:40:48,360 THESE MOVEMENT OF THIS COLOR 7768 04:40:48,360 --> 04:40:49,440 COATED AND WE CAN DO THE 7769 04:40:49,440 --> 04:40:51,440 KINETICS OF WHAT HAPPENED IN THE 7770 04:40:51,440 --> 04:40:53,000 CSF AND WHAT HAPPENS IN THE 7771 04:40:53,000 --> 04:40:53,360 TISSUE. 7772 04:40:53,360 --> 04:40:55,120 NOW, AS YOU LOOK AT T. IT'S 7773 04:40:55,120 --> 04:40:57,200 REALLY NOT VERY INFORMATIVE AND 7774 04:40:57,200 --> 04:40:59,520 WE HAVE LOOKED AT VERY BEAUTIFUL 7775 04:40:59,520 --> 04:41:00,960 IMAGES TODAY AND FOR ME, YOU 7776 04:41:00,960 --> 04:41:02,960 KNOW, THIS DOESN'T REEL TELL ME 7777 04:41:02,960 --> 04:41:05,760 ANYTHING ABOUT THE SPEED AND THE 7778 04:41:05,760 --> 04:41:07,200 BAD PHYSICAL NATURE OR THE 7779 04:41:07,200 --> 04:41:08,960 DIRECTION SO IN COLLABORATION 7780 04:41:08,960 --> 04:41:15,920 WITH Dr. TENENBAUM THE 7781 04:41:15,920 --> 04:41:16,840 MATHEMATICIAN AT SLOAN 7782 04:41:16,840 --> 04:41:18,160 KETTERING, HE HAS HELPED US AND 7783 04:41:18,160 --> 04:41:20,200 HE HAS DEVELOPED A COMPUTATIONAL 7784 04:41:20,200 --> 04:41:23,360 FLUID DYNAMICS, FRAMEWORK BASED 7785 04:41:23,360 --> 04:41:25,280 ON REGULAR TRANSPORT THEORY 7786 04:41:25,280 --> 04:41:30,360 WHICH IS A COMPLEX MATHEMATICAL 7787 04:41:30,360 --> 04:41:33,800 ALGORITHM THAT INCLUDES TWO KEY 7788 04:41:33,800 --> 04:41:37,920 TRANSPORT PROCESSES AND 7789 04:41:37,920 --> 04:41:39,480 DIFFUSION, I WON'T GO INTO THE 7790 04:41:39,480 --> 04:41:42,280 MATH IT'S NOT MY FOR PAY BUT 7791 04:41:42,280 --> 04:41:43,720 THIS PROCESSING PIPELINE SO WE 7792 04:41:43,720 --> 04:41:46,000 HAVE THE DYNAMIC IMAGES AND WE 7793 04:41:46,000 --> 04:41:47,880 FEED IT INTO THIS ALGORITHM AND 7794 04:41:47,880 --> 04:41:52,960 THIS IS WORK BY Dr. CHAN FROM 7795 04:41:52,960 --> 04:41:54,880 Dr. TENENBAUM'S LAB AND WE CAN 7796 04:41:54,880 --> 04:41:57,760 GET A LOT OF METRICS OF 7797 04:41:57,760 --> 04:41:58,080 INFORMATION. 7798 04:41:58,080 --> 04:42:03,400 WE CAN GET PATH LINE OF THE 7799 04:42:03,400 --> 04:42:11,080 NAND WE KNOWHOW FAST THE SOL USG 7800 04:42:11,080 --> 04:42:12,360 AND WE CAN GET NUMBERS THAT TELL 7801 04:42:12,360 --> 04:42:16,720 US IF THE MOVEMENT IS ADAPTIVE 7802 04:42:16,720 --> 04:42:18,680 OR DIFFUSION DOMINATED SO HERE 7803 04:42:18,680 --> 04:42:21,400 IS AN EXAMPLE, CAN YOU SEE, THAT 7804 04:42:21,400 --> 04:42:22,680 THERE'S DIRECTION AND WE CAN 7805 04:42:22,680 --> 04:42:26,840 ALSO GET MAGNITUDE OF THE 7806 04:42:26,840 --> 04:42:27,360 TRANSPORT. 7807 04:42:27,360 --> 04:42:30,520 QUICKLY I WANT TO SAY THAT THIS 7808 04:42:30,520 --> 04:42:31,160 MATHEMATICAL DATA CAN BE 7809 04:42:31,160 --> 04:42:37,880 PRESENTED IN TWO WAYS. 7810 04:42:37,880 --> 04:42:40,440 IN THE I'M SWIMMING IN THE RIVER 7811 04:42:40,440 --> 04:42:42,240 AND YOU GET THE WHOLE PATHWAY AS 7812 04:42:42,240 --> 04:42:44,840 I SWIM THROUGH THE RIVER HERE IN 7813 04:42:44,840 --> 04:42:48,080 EULER SO THIS IS EX LOCAL, 7814 04:42:48,080 --> 04:42:49,280 VELOCITY FLUX, LOCALLY IN THE 7815 04:42:49,280 --> 04:42:52,080 RAIN OVER A TIME FRAME FROM 640 7816 04:42:52,080 --> 04:42:58,000 TO 160 MINUTE ACT. 7817 04:42:58,000 --> 04:42:59,440 I CAN ALSO STAND HERE AND LOOK 7818 04:42:59,440 --> 04:43:00,880 AT THE RIVER AND SEE THE 7819 04:43:00,880 --> 04:43:03,000 SWIMMERS MOVING BY SO WE GET THE 7820 04:43:03,000 --> 04:43:04,560 TIMEFRAMES AND WE CAN LOOK AT 7821 04:43:04,560 --> 04:43:06,680 THE DIFFERENT STEPS AND THOSE 7822 04:43:06,680 --> 04:43:08,720 ARE DIFFERENT AND I HAVE A LOT 7823 04:43:08,720 --> 04:43:10,400 OF DIFFERENT INTERPRETATIONS. 7824 04:43:10,400 --> 04:43:12,320 SO HERE IS AN APPLICATION OF 7825 04:43:12,320 --> 04:43:14,720 THIS FRAMEWORK IN A RAT MODEL OF 7826 04:43:14,720 --> 04:43:17,680 SEVERAL AMYLOID AND THE AMYLOID 7827 04:43:17,680 --> 04:43:19,880 IS DEPOSITING ALONG THE VASCULAR 7828 04:43:19,880 --> 04:43:21,880 HERE IN THE RAT AND THESE RATS 7829 04:43:21,880 --> 04:43:24,320 GETS REALLY SICK AND 12 MONTHS 7830 04:43:24,320 --> 04:43:28,320 AND THEY'RE START TO GET MICRO 7831 04:43:28,320 --> 04:43:30,000 BLEEDS AND MIMICKING THE CLINIC 7832 04:43:30,000 --> 04:43:31,720 DISEASE AND THIS IS A 1-YEAR-OLD 7833 04:43:31,720 --> 04:43:34,320 RAT AND CAN YOU SEE SEE A NICE 7834 04:43:34,320 --> 04:43:38,040 PATTERN OF MOVEMENT AND MOVEMENT 7835 04:43:38,040 --> 04:43:39,800 INTO THE LYMPHATIC SYSTEM YOU 7836 04:43:39,800 --> 04:43:41,600 CAN SEE ALL THESE ARROWS OVER 7837 04:43:41,600 --> 04:43:44,440 HERE HIGHLIGHTED THAT THEY'RE 7838 04:43:44,440 --> 04:43:46,440 ACTIVELY MOVING TO THE LYMPHATIC 7839 04:43:46,440 --> 04:43:48,800 PATHWAY. 7840 04:43:48,800 --> 04:43:50,800 OVER HERE, YOU CAN SEE THE 7841 04:43:50,800 --> 04:43:52,720 DISEASE IS CAUSING THE CSF AND 7842 04:43:52,720 --> 04:43:56,520 FLOW TRAJECTORY T TO BY PASS, TY 7843 04:43:56,520 --> 04:43:58,320 CANNOT ACCESS THE LYMPHATIC 7844 04:43:58,320 --> 04:43:59,880 SYSTEM, THEY ARE ACTUALLY MOVING 7845 04:43:59,880 --> 04:44:02,760 TOWARDS THE FACTORY AND OTHER 7846 04:44:02,760 --> 04:44:04,920 EGRESS ROUTES AND THE LYMPHATIC 7847 04:44:04,920 --> 04:44:06,760 FLUX IS GETTING REDUCED AND WE 7848 04:44:06,760 --> 04:44:08,120 CAN QUANTIFY THIS. 7849 04:44:08,120 --> 04:44:09,800 BUT WE ALSO NEED TO SEE THE 7850 04:44:09,800 --> 04:44:11,360 CROSS TALK TO THE LYMPHATICS AND 7851 04:44:11,360 --> 04:44:14,040 THIS IS WHAT I WAS SAYING I'M 7852 04:44:14,040 --> 04:44:15,600 VENTURING OUT OF THE BLOOD BRAIN 7853 04:44:15,600 --> 04:44:18,680 BARRIER ON THE OTHER SIDE AND 7854 04:44:18,680 --> 04:44:20,240 HERE WE HAVE DEVELOPED RADIO 7855 04:44:20,240 --> 04:44:21,400 FREQUENCY CALL AT THE LEVEL OF 7856 04:44:21,400 --> 04:44:25,440 THE NECK AND WE USE A HIGHER 7857 04:44:25,440 --> 04:44:26,800 MOLECULAR CONTEST AGENCY TO GET 7858 04:44:26,800 --> 04:44:28,560 BETTER SIGNAL TO NOISE AND THESE 7859 04:44:28,560 --> 04:44:29,880 ARE ABOUT TWO MILLION DOLLARS 7860 04:44:29,880 --> 04:44:32,600 ACROSS ONE TO TWO MILLIMETERS 7861 04:44:32,600 --> 04:44:33,400 ACROSS THE LYMPHATIC NODES AND 7862 04:44:33,400 --> 04:44:37,720 THESE ARE THE DEEP OFFIC CERVICD 7863 04:44:37,720 --> 04:44:38,320 I MAPPED OUT JUST WHAT HAPPENED 7864 04:44:38,320 --> 04:44:45,160 AT THE LEVEL OF DEEP CERVICAL. 7865 04:44:45,160 --> 04:44:48,480 WE INJECT IT TO THE CSF AND 7866 04:44:48,480 --> 04:44:49,880 AFTER AN HOUR OR 70 MINUTES, 7867 04:44:49,880 --> 04:44:52,880 THIS IS WHERE THE CONTRAST PEAKS 7868 04:44:52,880 --> 04:44:57,600 AT THE LEVEL OF DEEP CERVICAL 7869 04:44:57,600 --> 04:44:58,360 LYMPH NODES AND THIS IS WHERE 7870 04:44:58,360 --> 04:45:00,120 THE CONTRAST FROM THE BRAIN GOES 7871 04:45:00,120 --> 04:45:01,520 AND THERE'S VERY LITTLE SPILL 7872 04:45:01,520 --> 04:45:03,240 OVER TO THE SUPERFICIAL NODES 7873 04:45:03,240 --> 04:45:05,120 AND THIS HAS BEEN CONFIRMED BY 7874 04:45:05,120 --> 04:45:05,680 MANY. 7875 04:45:05,680 --> 04:45:08,320 AND WE HAVE JUST NOW STARTED TO 7876 04:45:08,320 --> 04:45:09,640 EXPLORE IF WE CAN LOOK AT THESE 7877 04:45:09,640 --> 04:45:11,920 STREAMS GOING TO THE DEEP 7878 04:45:11,920 --> 04:45:14,160 CERVICAL, WHAT KIND OF BAD 7879 04:45:14,160 --> 04:45:16,160 PHYSICAL FORCE ARE DRIVERS THE 7880 04:45:16,160 --> 04:45:18,520 FLUIDS AND YOU CAN SEE IT LOOKS 7881 04:45:18,520 --> 04:45:19,440 LIKE AT LEAST SOME OF THE 7882 04:45:19,440 --> 04:45:23,520 STREAMS ALONG THE EXTERNAL OR 7883 04:45:23,520 --> 04:45:25,200 ARTED ARTERY INVECTIVE MOVES 7884 04:45:25,200 --> 04:45:26,960 TOWARDS THE DEEP CERVICAL BUT 7885 04:45:26,960 --> 04:45:28,640 AGAIN, THIS IS VERY EXPLORATORY. 7886 04:45:28,640 --> 04:45:29,680 THIS IS HOW WE HAVE APPLIED THIS 7887 04:45:29,680 --> 04:45:31,800 IN THE MODEL I JUST TOLD YOU 7888 04:45:31,800 --> 04:45:32,480 ABOUT. 7889 04:45:32,480 --> 04:45:34,960 IT HAS SEVERAL AMYLOID AND YOU 7890 04:45:34,960 --> 04:45:38,440 CAN SEE IN A NORMAL RAT PEAKS 7891 04:45:38,440 --> 04:45:41,400 AROUND AN HOUR TO 70 MINUTES AND 7892 04:45:41,400 --> 04:45:43,520 IN THE DECEASED RAT, THERE'S A 7893 04:45:43,520 --> 04:45:49,320 TIME DELAY AND THE MAGNITUDE -- 7894 04:45:49,320 --> 04:45:51,800 THE DEEP CERVICALES ARE 7895 04:45:51,800 --> 04:45:52,880 RECEIVING DRAINING BUT IT'S 7896 04:45:52,880 --> 04:45:57,000 TIMELY LTIMEDELAYED AND IT'S SPD 7897 04:45:57,000 --> 04:45:59,080 THIS IS TELLING US THE DRAINAGE 7898 04:45:59,080 --> 04:46:00,800 PATTERN HAS CHANGED. 7899 04:46:00,800 --> 04:46:03,240 THIS IS A MODEL OF CHRONIC 7900 04:46:03,240 --> 04:46:05,560 HYPERTENSION AND THIS IS DATA WE 7901 04:46:05,560 --> 04:46:07,760 HAVE NOT PUBLISHED BUT THESE 7902 04:46:07,760 --> 04:46:10,760 RODENT MODELS ARE MODELS OF 7903 04:46:10,760 --> 04:46:13,400 SMALL DISEASE IN THE BRAIN AND 7904 04:46:13,400 --> 04:46:16,120 THESE RATS ARE VERY HYPERTENSION 7905 04:46:16,120 --> 04:46:22,960 I HAVE, WE HAVE BRAIN AGE TO THE 7906 04:46:22,960 --> 04:46:24,640 DEEP CERVICAL AND SPILL OVER TO 7907 04:46:24,640 --> 04:46:28,520 THE SUPERVISION NOTE SO. 7908 04:46:28,520 --> 04:46:31,280 NOW WHAT HAPPENS IF WE BLOCK 7909 04:46:31,280 --> 04:46:32,720 DRAINAGE TO THE LYMPH NODES, 7910 04:46:32,720 --> 04:46:35,680 THIS IS WORK INSPIRED BY WORK IN 7911 04:46:35,680 --> 04:46:36,720 Dr. KIMNESS LAB. 7912 04:46:36,720 --> 04:46:40,400 I WANT TO HIGHLIGHT THE DOCTORS 7913 04:46:40,400 --> 04:46:42,160 AND WITHOUT THEIR WORK, THIS 7914 04:46:42,160 --> 04:46:44,280 WOULD NOT HAVE BEEN POSSIBLE AND 7915 04:46:44,280 --> 04:46:47,280 WE DEVELOPED AND MODELED WHERE 7916 04:46:47,280 --> 04:46:50,080 WE ACTUALLY CART ARISED A LOT 7917 04:46:50,080 --> 04:46:55,760 LYMPHATIC THAT SEEM TO ACTUALLY 7918 04:46:55,760 --> 04:46:57,200 RUN INTO THE DEEP CERVICAL LYMPH 7919 04:46:57,200 --> 04:46:59,360 NODES AND WE TESTED THIS 7920 04:46:59,360 --> 04:47:00,800 INHIBITS DRAINING TO THE DEEP 7921 04:47:00,800 --> 04:47:02,240 CERVICAL AS YOU CAN SEE HERE SO 7922 04:47:02,240 --> 04:47:05,120 THE MODEL SEEMS TO WORK AND WE 7923 04:47:05,120 --> 04:47:06,560 LET THESE RATS SURVIVE FOR ONE 7924 04:47:06,560 --> 04:47:09,400 MONTH AND AGAIN WE EXPLORE THIS 7925 04:47:09,400 --> 04:47:10,840 AND ONE OF THE FIRST THINGS THAT 7926 04:47:10,840 --> 04:47:13,760 I ASKED WAS, WHETHER OR NOT THEY 7927 04:47:13,760 --> 04:47:17,160 DEVELOPED HYDROCEPHALUS, DO THEY 7928 04:47:17,160 --> 04:47:18,560 DEVELOP INTERCRANIAL PRESSURE 7929 04:47:18,560 --> 04:47:20,520 AND THESE ARE VERY NEW DATA AND 7930 04:47:20,520 --> 04:47:23,400 YES WE DO SEE AN ELEVATION OF 7931 04:47:23,400 --> 04:47:24,920 INTERCRANIAL PRESSURE IN THESE 7932 04:47:24,920 --> 04:47:27,080 RATS AND THEY DO NOT HAVE NORMAL 7933 04:47:27,080 --> 04:47:28,720 DRAINAGE TO THE DEEP CERVICAL 7934 04:47:28,720 --> 04:47:36,240 BUT THEY DO NOT BECOME HYDRO SEV 7935 04:47:36,240 --> 04:47:39,280 ALI AND THIS IS CORRESPONDING 7936 04:47:39,280 --> 04:47:42,000 OPTIMAL MASS TRANSPORT ANALYSIS 7937 04:47:42,000 --> 04:47:45,600 OF THE DATA AND THIS IS FROM TWO 7938 04:47:45,600 --> 04:47:47,680 RATS UNDERGOING SHAM SURGERY AND 7939 04:47:47,680 --> 04:47:49,440 THIS IS MAPS SO THIS IS TELLING 7940 04:47:49,440 --> 04:47:54,960 US IF THE TRANSPORT IS 7941 04:47:54,960 --> 04:47:56,640 DIFFUSEIVE AND IN NORMAL RATS, 7942 04:47:56,640 --> 04:48:01,080 THIS IS THE LEVEL OF THE BEE AN 7943 04:48:01,080 --> 04:48:02,400 AND THE RECESS WHERE WE HAVE A 7944 04:48:02,400 --> 04:48:09,600 LOT OF CSF AND THE PATTERN HERE 7945 04:48:09,600 --> 04:48:10,920 IS YOU SEE WHAT HAPPENS IN THE 7946 04:48:10,920 --> 04:48:14,800 RAT THAT HAS IMPAIRED DRAINAGE, 7947 04:48:14,800 --> 04:48:19,240 YOU CAN SEE WE HAVE THESE VERY, 7948 04:48:19,240 --> 04:48:20,680 VERY STRONG STREAMS MOVING 7949 04:48:20,680 --> 04:48:22,200 TOWARDS THE RECESS AND WE ARE 7950 04:48:22,200 --> 04:48:23,520 STILL TRYING TO UNDERSTAND THIS 7951 04:48:23,520 --> 04:48:25,680 AND THIS IS JUST A MOVIE SHOWING 7952 04:48:25,680 --> 04:48:27,160 THE SAME THING AND I AM NOT 7953 04:48:27,160 --> 04:48:30,000 GOING TO SHOW YOU THE SHAM, I 7954 04:48:30,000 --> 04:48:31,760 JUST WANT YOU TO SHOW ONE HOUR 7955 04:48:31,760 --> 04:48:34,360 IN THIS IT'S THE OPTIMAL MASS 7956 04:48:34,360 --> 04:48:39,320 TRANSPORT ANALYSIS OF THE 7957 04:48:39,320 --> 04:48:41,000 VELOCITY FLUX VECTORS AND 7958 04:48:41,000 --> 04:48:42,880 THEY'RE SCREAMING VERY RAPIDLY 7959 04:48:42,880 --> 04:48:45,800 AND THERE'S A HIGH MAGNITUDE 7960 04:48:45,800 --> 04:48:50,880 VECTORS MOVING UP TOWARDS THE 7961 04:48:50,880 --> 04:48:53,040 RECESS AND I JUST WANT TO SAY SO 7962 04:48:53,040 --> 04:48:54,920 IN SUMMARY, WHAT HAVE I TOLD 7963 04:48:54,920 --> 04:48:55,920 YOU? 7964 04:48:55,920 --> 04:48:57,280 I'VE INVOLVED YOU ABOUT THE 7965 04:48:57,280 --> 04:48:59,640 DYNAMIC CONTEST ENHANCED IN 7966 04:48:59,640 --> 04:49:02,200 MODALITY AND THE COMPUTATIONAL 7967 04:49:02,200 --> 04:49:03,320 FLUID ALGORITHM WE HAVE 7968 04:49:03,320 --> 04:49:09,560 DEVELOPED TO LOOK AT LYMPHATIC 7969 04:49:09,560 --> 04:49:09,800 SYSTEM. 7970 04:49:09,800 --> 04:49:12,520 I'VE SHOWED YOU APPLICATIONS 7971 04:49:12,520 --> 04:49:13,720 THAT WE CAN START TO TEASE OUT 7972 04:49:13,720 --> 04:49:16,800 WHAT IS HAPPENING IN THE NEW 7973 04:49:16,800 --> 04:49:19,200 DEGENERATIVE DISORDERS IN IN 7974 04:49:19,200 --> 04:49:21,120 SEVERAL SMALL VESSEL DISEASE AND 7975 04:49:21,120 --> 04:49:22,600 WE ARE JUST NOW STARTING TO 7976 04:49:22,600 --> 04:49:28,520 EXPLORE THE COUPLING BETWEEN THE 7977 04:49:28,520 --> 04:49:31,480 LYMPHATIC AND GLYMPHATIC SYSTEM 7978 04:49:31,480 --> 04:49:33,880 AND DOING THAT BY STARTING TO 7979 04:49:33,880 --> 04:49:35,400 BLOCK THE MAIN HOPS FOR THE 7980 04:49:35,400 --> 04:49:37,640 DRAINAGE AND WE'RE DOING PROFILE 7981 04:49:37,640 --> 04:49:41,320 UP MARKER, PROFILING IN 7982 04:49:41,320 --> 04:49:42,360 COLLABORATION WITH CERTAIN AND 7983 04:49:42,360 --> 04:49:43,720 WE ARE ALSO LOOKING AT WHAT 7984 04:49:43,720 --> 04:49:47,160 HAPPENED WITH KEY WASTE PROTEINS 7985 04:49:47,160 --> 04:49:49,400 LIKE PTAU WITH Dr. XIE. 7986 04:49:49,400 --> 04:49:55,000 I WANT TO THANK MY COLLABORATORS 7987 04:49:55,000 --> 04:49:58,040 AND YALE, THE STONY BROOK STEAM, 7988 04:49:58,040 --> 04:50:00,720 WITHOUT THEM WE CON INTERPRET OR 7989 04:50:00,720 --> 04:50:06,840 GET ALL THESE VARIABLE DATA AND 7990 04:50:06,840 --> 04:50:08,720 Dr. KIPNESS AND WHO IS DOING 7991 04:50:08,720 --> 04:50:11,600 THE OMICS ANALYSIS OF SOME OF 7992 04:50:11,600 --> 04:50:14,080 THE NEW STARTERS WHERE WE ARE 7993 04:50:14,080 --> 04:50:16,320 BLOCKING DRAINAGE. 7994 04:50:16,320 --> 04:50:17,640 AND GAPS NEEDS AN OPPORTUNITIES 7995 04:50:17,640 --> 04:50:18,720 THAT ARE MANY. 7996 04:50:18,720 --> 04:50:20,520 THESE ARE JUST SOME OF THEM. 7997 04:50:20,520 --> 04:50:22,880 BUT I THINK THE BIGGEST ONES ARE 7998 04:50:22,880 --> 04:50:25,240 TO UNDERSTAND THE DRIVING FORCES 7999 04:50:25,240 --> 04:50:26,400 OF HOW THINGS ARE ACTUALLY 8000 04:50:26,400 --> 04:50:27,600 MOVING FROM THE BRAIN AND OUT 8001 04:50:27,600 --> 04:50:31,880 AND I KNOW PEOPLE ARE SAYING IT 8002 04:50:31,880 --> 04:50:33,720 REACHES THE LYMPHATIC AND THE 8003 04:50:33,720 --> 04:50:36,120 NODES BUT CLEARLY THAT IS NOT 8004 04:50:36,120 --> 04:50:37,400 TRUE BECAUSE WITHOUT 8005 04:50:37,400 --> 04:50:38,840 UNDERSTANDING THE DRIVING 8006 04:50:38,840 --> 04:50:40,840 FORCES, WE ALSO WON BE ABLE TO 8007 04:50:40,840 --> 04:50:43,320 DEVELOP THE THERAPEUTICS AND I 8008 04:50:43,320 --> 04:50:45,240 ALSO WOULD VERY MUCH HIGHLIGHT 8009 04:50:45,240 --> 04:50:47,400 WE NEED NON-INVASIVE IMAGES 8010 04:50:47,400 --> 04:50:48,560 METHODS TO TRACK THE SAME THING 8011 04:50:48,560 --> 04:50:51,160 IN THE HUMAN BRAIN WITHOUT 8012 04:50:51,160 --> 04:50:51,440 CONTRAST. 8013 04:50:51,440 --> 04:50:54,000 THANK YOU FOR YOUR ATTENTION. 8014 04:50:54,000 --> 04:50:57,120 >> WOW, THANK YOU SO MUCH, 8015 04:50:57,120 --> 04:50:58,600 HELENE, IT WAS A BEAUTIFUL TALK. 8016 04:50:58,600 --> 04:51:00,520 NOW WE HAVE OUR 10-MINUTES OF 8017 04:51:00,520 --> 04:51:02,640 MODERATION AND WE HAVE LOTS OF 8018 04:51:02,640 --> 04:51:04,240 QUESTIONS SO, FOR THOSE OF YOU 8019 04:51:04,240 --> 04:51:05,800 WHO ARE HOSTING PANELS WHO HAVE 8020 04:51:05,800 --> 04:51:07,280 ASKED QUESTIONS TO EACH A. RAISE 8021 04:51:07,280 --> 04:51:12,160 OTHER, RAISEYOUR HAND AND I'LL . 8022 04:51:12,160 --> 04:51:14,080 THE FIRST QUESTION IS A PATIENTS 8023 04:51:14,080 --> 04:51:16,200 ON THE PANEL, CYNTHIA HUDSON. 8024 04:51:16,200 --> 04:51:21,600 IN THIS QUESTION IS FOR Dr. 8025 04:51:21,600 --> 04:51:21,800 DORI. 8026 04:51:21,800 --> 04:51:22,120 THANK YOU. 8027 04:51:22,120 --> 04:51:23,840 LET ME TROY AND FIND IT HERE. 8028 04:51:23,840 --> 04:51:25,240 HAVE THERE BEEN STUDIES ON THE 8029 04:51:25,240 --> 04:51:30,000 LONG-TERM EFFECTS OF TAKING 8030 04:51:30,000 --> 04:51:31,360 TRAMIGHTENAB AND THERE ARE A LOT 8031 04:51:31,360 --> 04:51:33,000 OF QUESTIONS. 8032 04:51:33,000 --> 04:51:35,920 MECHANISMS OF AVER ACTION. 8033 04:51:35,920 --> 04:51:37,560 WHAT DO YOU KNOW? 8034 04:51:37,560 --> 04:51:37,920 UNLOAD IT HERE. 8035 04:51:37,920 --> 04:51:40,800 THANK YOU SO MUCH AND THANK YOU, 8036 04:51:40,800 --> 04:51:44,840 THIN SEE CYNTHIA. 8037 04:51:44,840 --> 04:51:46,480 >> SO THOSE ARE ALL EXCELLENT 8038 04:51:46,480 --> 04:51:46,720 QUESTIONS. 8039 04:51:46,720 --> 04:51:48,400 THE ANSWER TO THE QUESTIONS ARE 8040 04:51:48,400 --> 04:51:49,720 PRETTY MUCH YOU KNOW, THAT 8041 04:51:49,720 --> 04:51:52,320 THERE'S A WHOLE BUNCH OF GAPS OF 8042 04:51:52,320 --> 04:51:53,360 KNOWLEDGE AS FAR AS -- SO WE 8043 04:51:53,360 --> 04:51:56,120 KNOW MECHANISMS ARE ACTION IS 8044 04:51:56,120 --> 04:51:59,080 IT'S A INHIBITOR. 8045 04:51:59,080 --> 04:52:01,320 WHAT ACTUALLY IT IS DOING, HOW 8046 04:52:01,320 --> 04:52:04,920 IT IS ALTERING THE LYMPH SYSTEM 8047 04:52:04,920 --> 04:52:07,440 WHY THINK WE COMPLETELY 8048 04:52:07,440 --> 04:52:08,320 UNDERSTAND THAT. 8049 04:52:08,320 --> 04:52:10,520 SARAH SHEPHERD FROM THE NIH WHO 8050 04:52:10,520 --> 04:52:12,440 WE WORKED ALL TOGETHER HAS A 8051 04:52:12,440 --> 04:52:15,000 GROUP, HAVE THE ANIMAL MODELS 8052 04:52:15,000 --> 04:52:16,440 AND ALL THOSE THINGS WHERE 8053 04:52:16,440 --> 04:52:18,680 THEY'RE STARTING TO DO EXACTLY 8054 04:52:18,680 --> 04:52:20,640 THAT TO FIGURE OUT WHAT ARE THE 8055 04:52:20,640 --> 04:52:22,160 FUNCTIONAL EFFECTS OF THESE 8056 04:52:22,160 --> 04:52:25,320 DRUGS LIKE WHAT ARE THE PATHWAYS 8057 04:52:25,320 --> 04:52:26,160 THEY EFFECT. 8058 04:52:26,160 --> 04:52:28,440 AGAIN, WHEN WE STARTED TREATING 8059 04:52:28,440 --> 04:52:32,360 PEOPLE AND WE DID IT FIRST FOR A 8060 04:52:32,360 --> 04:52:36,920 PATIENT WHO IS NOT A KLA PATIENT 8061 04:52:36,920 --> 04:52:38,280 BUT A CONDUCTION DISORDER WE DID 8062 04:52:38,280 --> 04:52:39,320 IT BASED ON FISH DATA. 8063 04:52:39,320 --> 04:52:40,840 WE SAW THE EFFECTS ON A FISH 8064 04:52:40,840 --> 04:52:42,120 DATA AND WE HAD A PATIENT WHO 8065 04:52:42,120 --> 04:52:44,360 WAS DYING FROM HIS DISEASE, AND 8066 04:52:44,360 --> 04:52:46,400 IT AGAIN QUICKLY REVERSED IT. 8067 04:52:46,400 --> 04:52:49,720 BUT IT WAS NEVER TRIED BEFORE. 8068 04:52:49,720 --> 04:52:52,480 WE USED USUALLY A LOWER DOSE FOR 8069 04:52:52,480 --> 04:52:54,360 THESE PATIENTS SO THAT THE 8070 04:52:54,360 --> 04:52:55,840 TOLERANCE IS USUALLY PRETTY WELL 8071 04:52:55,840 --> 04:52:57,320 AND THE MOST COMMON SIDE EFFECT 8072 04:52:57,320 --> 04:53:01,200 THAT WE SEE IS A RASH. 8073 04:53:01,200 --> 04:53:02,960 AND BECAUSE THE PATIENTS THAT 8074 04:53:02,960 --> 04:53:04,520 WE'RE TREATING WHERE THE DRUG 8075 04:53:04,520 --> 04:53:06,280 WORKS, IT DOESN'T WORK ON 8076 04:53:06,280 --> 04:53:06,680 EVERYBODY. 8077 04:53:06,680 --> 04:53:08,880 WE THINK IT REALLY WORKS ON GAIN 8078 04:53:08,880 --> 04:53:10,400 OF FUNCTION MUTATIONS WITHIN THE 8079 04:53:10,400 --> 04:53:15,440 PATHWAY THAT ARE RAMPING UP THE 8080 04:53:15,440 --> 04:53:17,240 PATHWAY SO IT MAKES SENSE. 8081 04:53:17,240 --> 04:53:19,240 ON PATIENTS, BECAUSE THEY HAVE 8082 04:53:19,240 --> 04:53:20,800 THAT ABNORMAL PART OF THE 8083 04:53:20,800 --> 04:53:22,200 PATHWAY, THE DRUG IS JUST 8084 04:53:22,200 --> 04:53:23,840 BASICALLY NORMALIZING THINGS 8085 04:53:23,840 --> 04:53:26,280 BACK DOWN, AND WE PUBLISHED ALSO 8086 04:53:26,280 --> 04:53:28,680 ABOUT A PATIENT WE TREATED AND 8087 04:53:28,680 --> 04:53:30,760 THERE WERE MULTIPLE ORGANS 8088 04:53:30,760 --> 04:53:31,840 EFFECTS BY TREATING WITH THE 8089 04:53:31,840 --> 04:53:34,080 DRUG AT A RELATIVELY LOW DOSE. 8090 04:53:34,080 --> 04:53:35,520 WE DON'T USE THE SAME DOSE AS 8091 04:53:35,520 --> 04:53:37,040 THEY USE FOR CHEMOTHERAPY TO 8092 04:53:37,040 --> 04:53:38,000 TREAT THIS. 8093 04:53:38,000 --> 04:53:38,480 NOW? 8094 04:53:38,480 --> 04:53:40,360 ADDITION TO THAT, BECAUSE I 8095 04:53:40,360 --> 04:53:44,600 MEAN, SO ALLEN TENENBAUM AND I 8096 04:53:44,600 --> 04:53:47,240 ARE ACTUALLY VERY, VERY CLOSE 8097 04:53:47,240 --> 04:53:48,400 FRIENDS. 8098 04:53:48,400 --> 04:53:51,440 OUTSIDE OF THE SCIENCE, BUT WE 8099 04:53:51,440 --> 04:53:52,480 HAVE BEEN TALKING TOGETHER WITH 8100 04:53:52,480 --> 04:53:54,000 A GROUP OF PRINCETON ABOUT USING 8101 04:53:54,000 --> 04:53:55,440 THESE DRUGS IN COMBINATIONS OF 8102 04:53:55,440 --> 04:53:56,720 OTHER DRUGS AND THERE'S A TRIAL 8103 04:53:56,720 --> 04:53:58,120 THAT'S GOING TO BE DONE FOR 8104 04:53:58,120 --> 04:53:58,480 THAT. 8105 04:53:58,480 --> 04:53:59,680 BUT THERE'S A LOT ABOUT THE 8106 04:53:59,680 --> 04:54:01,000 DIFFERENT PATHWAYS AND HOW THESE 8107 04:54:01,000 --> 04:54:03,280 DRUGS ARE FUNCTIONING THAT WE 8108 04:54:03,280 --> 04:54:04,320 SIMPLY DON'T UNDERSTAND. 8109 04:54:04,320 --> 04:54:06,120 WITH THOSE WHO HAVE ACTIVATION 8110 04:54:06,120 --> 04:54:08,880 OF THE PATHWAY AND YOU PUT THEM 8111 04:54:08,880 --> 04:54:10,760 ON TREE MENTIVE, IT DOES 8112 04:54:10,760 --> 04:54:11,320 WONDERS. 8113 04:54:11,320 --> 04:54:14,320 THEY TOLERATE IT WELL AND WEST 8114 04:54:14,320 --> 04:54:16,200 KEPT THEM ON IT FOR YEARS WITH 8115 04:54:16,200 --> 04:54:17,040 FEW SIDE EFFECTS. 8116 04:54:17,040 --> 04:54:18,000 >> THANK YOU FOR THAT. 8117 04:54:18,000 --> 04:54:18,800 >> NO PROBLEM. 8118 04:54:18,800 --> 04:54:20,240 >> THANK YOU, BOTH. 8119 04:54:20,240 --> 04:54:21,840 YEAH, YOU HAD SO MANY QUESTIONS 8120 04:54:21,840 --> 04:54:24,240 IN THE CHAT FOR BOTH MAX AND 8121 04:54:24,240 --> 04:54:25,760 YOAV SO I'M CALLING ON YOU NEXT 8122 04:54:25,760 --> 04:54:27,200 AND I'LL WORK OUR WAY THROUGH. 8123 04:54:27,200 --> 04:54:30,280 THANK YOU, GUYS. 8124 04:54:30,280 --> 04:54:31,000 >> THANK YOU. 8125 04:54:31,000 --> 04:54:33,760 THANK YOU Dr. DORI AND MAX. 8126 04:54:33,760 --> 04:54:35,920 IT'S SUCH A FANTASTIC AND 8127 04:54:35,920 --> 04:54:36,640 EXCITING TALK. 8128 04:54:36,640 --> 04:54:41,040 SO MY QUESTION IS ABOUT THE 8129 04:54:41,040 --> 04:54:43,640 LIVER CAP YOU LAR LYMPHATIC 8130 04:54:43,640 --> 04:54:45,640 SYSTEM WHICH IS NOT STUDIED BUT 8131 04:54:45,640 --> 04:54:46,960 IT'S VERY IMPORTANT, 8132 04:54:46,960 --> 04:54:49,280 PARTICULARLY IN HUMAN CAN SEE A 8133 04:54:49,280 --> 04:54:51,200 LOT OF LYMPHATIC VESSEL DEVELOP 8134 04:54:51,200 --> 04:54:53,640 IN THE CAPSULAR AREA. 8135 04:54:53,640 --> 04:54:57,360 MY QUESTION IS, LIVER CAP YOU 8136 04:54:57,360 --> 04:54:58,920 LAR LYMPHATIC VESSEL COMMUNICATE 8137 04:54:58,920 --> 04:55:03,680 WITH PORTAL LYMPHATIC VESSEL BUT 8138 04:55:03,680 --> 04:55:05,880 THE DRIVEN TO THE SAME LYMPH 8139 04:55:05,880 --> 04:55:08,680 NODE AS THE PORTAL LYMPH NODE 8140 04:55:08,680 --> 04:55:11,760 ARE THERE ANY COMMUNICATION 8141 04:55:11,760 --> 04:55:18,640 BETWEEN THE LUNG LYMPHATICS? 8142 04:55:18,640 --> 04:55:23,280 >> SO, DEFINITELY THE LIVER 8143 04:55:23,280 --> 04:55:26,440 LYMPHATICS CAP ZOO LAR AND 8144 04:55:26,440 --> 04:55:29,640 SOMETIMES EVEN LYMPHATIC 8145 04:55:29,640 --> 04:55:35,120 COMMUNICATE THROUGH WITH THE 8146 04:55:35,120 --> 04:55:37,680 (INAUDIBLE), THAT'S ATOMICAL TO 8147 04:55:37,680 --> 04:55:40,120 ME BUT I THINK IN THE PAPERS YOU 8148 04:55:40,120 --> 04:55:41,560 ARE ACTUALLY RIGHT IT SHOWS IT. 8149 04:55:41,560 --> 04:55:46,240 WE SEE IT IN CLINICAL, OF 8150 04:55:46,240 --> 04:55:51,760 COURSE, SUCH BRONCHITIS, PLURAL 8151 04:55:51,760 --> 04:55:53,400 INFLATION AND MAYBE SOME OTHER 8152 04:55:53,400 --> 04:55:55,680 DISEASES WE DIDN'T DISCOVER YET 8153 04:55:55,680 --> 04:55:58,200 BECAUSE UNFORTUNATELY WE HAVE 8154 04:55:58,200 --> 04:55:58,800 TOOLS RIGHT. 8155 04:55:58,800 --> 04:56:01,120 SO PEOPLE DO KNOW HOW TO REFER 8156 04:56:01,120 --> 04:56:02,440 TO US. 8157 04:56:02,440 --> 04:56:03,840 IN MY INSTITUTION WHEN PEOPLE 8158 04:56:03,840 --> 04:56:06,840 ASK WHAT PATIENT WE HAVE TO 8159 04:56:06,840 --> 04:56:08,840 REFER TO, THE ANSWER IS 8160 04:56:08,840 --> 04:56:12,880 SOMETHING LEAKING SOMETHING 8161 04:56:12,880 --> 04:56:16,760 SWOLLEN OR COMPLETELY LOST AND 8162 04:56:16,760 --> 04:56:18,080 70% OF THE TIME WE FIND 8163 04:56:18,080 --> 04:56:20,400 SOMETHING LYMPHATIC RELATED TO 8164 04:56:20,400 --> 04:56:20,600 THAT. 8165 04:56:20,600 --> 04:56:22,920 WE HAVE DEFINITELY THERE'S 8166 04:56:22,920 --> 04:56:26,200 PATHOLOGY MECHANISM OF CERTAIN 8167 04:56:26,200 --> 04:56:26,760 DISEASES BUT WE'LL DISCOVER 8168 04:56:26,760 --> 04:56:28,720 PROBLEM MORE AND MORE IN THE 8169 04:56:28,720 --> 04:56:29,400 FUTURE. 8170 04:56:29,400 --> 04:56:31,360 FOR SURE. 8171 04:56:31,360 --> 04:56:34,400 THIS IS SOMEONE ELSE'S QUESTION? 8172 04:56:34,400 --> 04:56:39,240 SO GENERALLY THE IS COMPLEX. 8173 04:56:39,240 --> 04:56:41,360 THERE'S MULTIPLE COMMUNICATIONS 8174 04:56:41,360 --> 04:56:42,520 FROM DIFFERENT EVERYWHERE THE 8175 04:56:42,520 --> 04:56:48,160 LIVER ATTACHED TO THE SURFACE OF 8176 04:56:48,160 --> 04:56:51,680 THE PER TEENIAL IT'S 8177 04:56:51,680 --> 04:56:52,720 COMMUNICATIONS AND THAT'S 8178 04:56:52,720 --> 04:56:53,840 SOMETIMES IT'S DIFFICULT TO 8179 04:56:53,840 --> 04:56:54,080 PREDICT. 8180 04:56:54,080 --> 04:56:55,760 YOU HAVE TO IMAGE ALL OF THOSE. 8181 04:56:55,760 --> 04:56:57,280 SOMETIMES IMAGING IS DIFFICULT 8182 04:56:57,280 --> 04:56:58,960 BECAUSE IMAGE ONE PART OF THE 8183 04:56:58,960 --> 04:57:01,800 LYMPHATIC SYSTEM AND DIDN'T SEE 8184 04:57:01,800 --> 04:57:03,120 THE OTHER ONE THAT DOESN'T FEEL 8185 04:57:03,120 --> 04:57:05,600 FROM THIS SO IT'S A COMPLEX 8186 04:57:05,600 --> 04:57:09,000 ISSUE OF COURSE. 8187 04:57:09,000 --> 04:57:11,240 AND GEOGRAPHY OF THE LIVER HELPS 8188 04:57:11,240 --> 04:57:12,760 SIGNIFICANT TO UNDERSTAND THAT. 8189 04:57:12,760 --> 04:57:19,080 >> SO THE LYMPHATIC VESSEL DRAIN 8190 04:57:19,080 --> 04:57:21,640 TO DIFFERENT LYMPH NODE COMPARED 8191 04:57:21,640 --> 04:57:21,840 TO? 8192 04:57:21,840 --> 04:57:25,960 >> YEAH, THEY COMMUNICATE 8193 04:57:25,960 --> 04:57:26,320 (INAUDIBLE). 8194 04:57:26,320 --> 04:57:29,720 >> SO DEFINITELY, YEAH. 8195 04:57:29,720 --> 04:57:31,880 IT WAS LYMPH NODES OR LYMPHATIC 8196 04:57:31,880 --> 04:57:32,160 STRUCTURES. 8197 04:57:32,160 --> 04:57:33,880 >> THEY'RE DIFFERENT. 8198 04:57:33,880 --> 04:57:34,040 OK. 8199 04:57:34,040 --> 04:57:37,000 >> IF I ADD ONE THING TO THAT, I 8200 04:57:37,000 --> 04:57:38,600 MEAN, IF YOU LOOK AT THAT 8201 04:57:38,600 --> 04:57:39,800 ARTICLE YOU PUBLISHED ABOUT THE 8202 04:57:39,800 --> 04:57:41,040 DIFFERENT CONNECTIONS, THE 8203 04:57:41,040 --> 04:57:45,160 DRAINING TO THE LYMPH NODES, CAP 8204 04:57:45,160 --> 04:57:46,440 SIL I AM FAD I CAN DRAIN UP BUT 8205 04:57:46,440 --> 04:57:47,680 DIFFERENT PARTS OF THE LIVER 8206 04:57:47,680 --> 04:57:49,680 DON'T CONNECT TO THE CAPSULE OR 8207 04:57:49,680 --> 04:57:51,160 LYMPHATICS THAT ARE DRAINING UP. 8208 04:57:51,160 --> 04:57:52,800 SO IF YOU ACCESS DIFFERENT 8209 04:57:52,800 --> 04:57:54,480 PORTIONS OF THE LIVER, YOU WILL 8210 04:57:54,480 --> 04:57:55,640 GET SOME CONNECTIONS THAT ARE 8211 04:57:55,640 --> 04:57:56,920 CONNECTING TO THE CAPSULE THAT 8212 04:57:56,920 --> 04:57:59,920 THEN GO UP AND IN CERTAIN 8213 04:57:59,920 --> 04:58:01,440 PORTIONS OF THE LIVER, DRAINING 8214 04:58:01,440 --> 04:58:03,960 IS GOING DOWN AND UNDER NORMAL 8215 04:58:03,960 --> 04:58:07,520 CONDITIONS, YOU WON'T SEE IT UP 8216 04:58:07,520 --> 04:58:09,600 INTO THE LUNG. 8217 04:58:09,600 --> 04:58:10,680 BUT HAVING LUNG LYMPHATICS FOR 8218 04:58:10,680 --> 04:58:12,080 EXAMPLE IN THE PAPER I TALKED 8219 04:58:12,080 --> 04:58:16,040 ABOUT, THE GONE OWE PHENOTYPE 8220 04:58:16,040 --> 04:58:18,440 YOU SEE MUTATION YOU DON'T SEE A 8221 04:58:18,440 --> 04:58:21,080 THORACIC DUCT BUT CAPSULE 8222 04:58:21,080 --> 04:58:22,800 LYMPHATICS PUNCTURING ACROSS THE 8223 04:58:22,800 --> 04:58:24,360 DIAPHRAGM GOING UP TO THE 8224 04:58:24,360 --> 04:58:28,160 BRONCHIAL LYMPHATICS AND THERE 8225 04:58:28,160 --> 04:58:28,760 ARE LYMPH NODES THERE BUT I'M 8226 04:58:28,760 --> 04:58:30,600 NOT SURE EXACTLY -- THE LYMPH 8227 04:58:30,600 --> 04:58:31,720 NODES ARE THERE BUT I'M NOT SURE 8228 04:58:31,720 --> 04:58:33,160 IF IT'S DRAINING TOWARDS THEM OR 8229 04:58:33,160 --> 04:58:34,360 IF THAT'S THE PATHWAY IT TAKES. 8230 04:58:34,360 --> 04:58:35,560 >> THANK YOU, VERY MUCH FOR 8231 04:58:35,560 --> 04:58:35,960 BOTH. 8232 04:58:35,960 --> 04:58:37,440 IT'S VERY INTERESTING. 8233 04:58:37,440 --> 04:58:38,360 >> THANK YOU BOTH. 8234 04:58:38,360 --> 04:58:43,320 AND SO, NILS, YOU ARE ON DECK 8235 04:58:43,320 --> 04:58:45,000 NECK AND CELINE WILL ASK A 8236 04:58:45,000 --> 04:58:45,280 QUESTION. 8237 04:58:45,280 --> 04:58:48,240 THIS IS A REALLY GOOD HIGH-LEVEL 8238 04:58:48,240 --> 04:58:50,640 QUESTION FROM THE AUDIENCE. 8239 04:58:50,640 --> 04:58:52,360 WHAT TOOLS OR VISUALIZATIONS 8240 04:58:52,360 --> 04:58:54,960 EXIST TO TRANSLATE DATA TO HELP 8241 04:58:54,960 --> 04:58:56,400 RESEARCHERS, PHYSICIANS AND 8242 04:58:56,400 --> 04:58:57,480 PATIENTS MAKE BETTER DECISIONS 8243 04:58:57,480 --> 04:58:57,920 TOGETHER. 8244 04:58:57,920 --> 04:58:59,840 I LIKE THE TOGETHER ASPECT. 8245 04:58:59,840 --> 04:59:02,120 >> THANK YOU FOR THE QUESTION. 8246 04:59:02,120 --> 04:59:06,640 AND I THINK THIS IS IN DEED AN 8247 04:59:06,640 --> 04:59:09,640 EXCELLENT QUESTION. 8248 04:59:09,640 --> 04:59:11,600 I WANT TO EMPHASIS THE TOGETHER 8249 04:59:11,600 --> 04:59:12,600 ASPECT OF THIS QUESTION. 8250 04:59:12,600 --> 04:59:14,440 IT'S QUITE DIFFERENT, I THINK, 8251 04:59:14,440 --> 04:59:16,600 FROM WHAT I SHOWED TODAY. 8252 04:59:16,600 --> 04:59:19,400 SO WHAT I SHOWED TODAY, THESE 8253 04:59:19,400 --> 04:59:22,360 VISUALIZATIONS ARE TARGETED TO 8254 04:59:22,360 --> 04:59:24,840 RESEARCHERS, RIGHT. 8255 04:59:24,840 --> 04:59:26,320 THIS IS DATA FAIRLY RAW DATA IN 8256 04:59:26,320 --> 04:59:28,360 A WAY ALTHOUGH IT'S VISUAL, AND 8257 04:59:28,360 --> 04:59:32,000 IT HELPS WITH UNDERSTANDING SOME 8258 04:59:32,000 --> 04:59:34,640 BASICS AT THE MOLECULAR LEVEL. 8259 04:59:34,640 --> 04:59:36,720 IF YOU ARE INTERESTED IN MAKING 8260 04:59:36,720 --> 04:59:38,040 DECISIONS TOGETHER, SORT OF A 8261 04:59:38,040 --> 04:59:39,920 SHARED DECISION-MAKING 8262 04:59:39,920 --> 04:59:41,120 VISUALIZATION, WHAT WE NEED TO 8263 04:59:41,120 --> 04:59:44,520 TAKE INTO ACCOUNT, THIS HAPPENS 8264 04:59:44,520 --> 04:59:46,160 TO BE ANOTHER AREA OF MY 8265 04:59:46,160 --> 04:59:47,560 RESEARCH IS WHAT IMPLICATIONS 8266 04:59:47,560 --> 04:59:48,760 WOULD THESE DECISIONS HAVE ON 8267 04:59:48,760 --> 04:59:50,320 THE PATIENTS, RIGHT. 8268 04:59:50,320 --> 04:59:52,000 SO YOU ARE INTERESTED IN 8269 04:59:52,000 --> 04:59:53,600 UNDERSTANDING POTENTIAL 8270 04:59:53,600 --> 04:59:55,040 OUTCOMES, RISKS ASSOCIATED WITH 8271 04:59:55,040 --> 04:59:58,640 CERTAIN STRATEGIES, TREATMENTS, 8272 04:59:58,640 --> 05:00:00,480 ET CETERA, BUT EVEN THOUGH IT'S 8273 05:00:00,480 --> 05:00:02,680 NOT A TRIVIAL PROBLEM TO SOLVE, 8274 05:00:02,680 --> 05:00:06,680 I THINK IT IS REALLY A VERY 8275 05:00:06,680 --> 05:00:09,800 IMPORTANT DIRECTION OF RESEARCH 8276 05:00:09,800 --> 05:00:11,240 TO UNDERTAKE BECAUSE IN FACT, 8277 05:00:11,240 --> 05:00:13,080 DATA VISUALIZATION CAN BE AN 8278 05:00:13,080 --> 05:00:16,280 EXCELLENT TOOL FOR COMMUNICATION 8279 05:00:16,280 --> 05:00:18,560 BETWEEN STAKEHOLDERS BUT 8280 05:00:18,560 --> 05:00:19,600 DIFFERENT LEVELS OF 8281 05:00:19,600 --> 05:00:21,760 UNDERSTANDING OFF THE PROBLEM 8282 05:00:21,760 --> 05:00:23,880 AND DIFFERENT PERSPECTIVES SO WE 8283 05:00:23,880 --> 05:00:26,480 HAVE DONE SOME WORK ON POTENTIAL 8284 05:00:26,480 --> 05:00:27,920 OUTCOMES OF SURGERIES, AND 8285 05:00:27,920 --> 05:00:29,600 DIFFERENT TYPES OF SURGERIES AND 8286 05:00:29,600 --> 05:00:30,800 HOW THIS WOULD ACT OF PATIENT 8287 05:00:30,800 --> 05:00:36,880 AND THEIR TRAJECTORY AND SO IT'S 8288 05:00:36,880 --> 05:00:37,840 A GREAT OPPORTUNITY TO GET 8289 05:00:37,840 --> 05:00:39,880 PEOPLE AT THE SAME TABLE SO 8290 05:00:39,880 --> 05:00:41,160 LEVEL THE PLAYING FIELD A LITTLE 8291 05:00:41,160 --> 05:00:43,920 BIT SO THAT PATIENTS CAN ASK THE 8292 05:00:43,920 --> 05:00:45,080 QUESTIONS ABOUT THEIR CONDITION 8293 05:00:45,080 --> 05:00:46,400 AND ABOUT POTENTIAL TREATMENTS 8294 05:00:46,400 --> 05:00:47,800 BASED ON THE DATA THAT'S BEEN 8295 05:00:47,800 --> 05:00:51,360 PRESENTED TO THEM. 8296 05:00:51,360 --> 05:00:53,480 >> THANK YOU SO MUCH, NILS. 8297 05:00:53,480 --> 05:00:55,120 AND IF THAT WAS A GREAT QUESTION 8298 05:00:55,120 --> 05:00:59,720 AND WE'LL ASK SALEN TO ASK A 8299 05:00:59,720 --> 05:01:02,160 QUESTION TO HELENE. 8300 05:01:02,160 --> 05:01:03,040 >> ALL THE TALKS WERE GREAT AND 8301 05:01:03,040 --> 05:01:04,840 THANK YOU FOR THIS GREAT 8302 05:01:04,840 --> 05:01:05,400 SESSION. 8303 05:01:05,400 --> 05:01:08,080 I WAS GOING TO ASK HELENE, IT 8304 05:01:08,080 --> 05:01:09,920 MIGHT BE, I GUESS IT APPLIES TO 8305 05:01:09,920 --> 05:01:12,320 ALL THE ORGAN SYSTEMS WE SAW BUT 8306 05:01:12,320 --> 05:01:14,560 IS THERE A POSSIBILITY THAT THE 8307 05:01:14,560 --> 05:01:16,400 INDIVIDUAL VARIANTS IN THE 8308 05:01:16,400 --> 05:01:19,800 ANATOMICAL PATHWAYS OF THE GLIM 8309 05:01:19,800 --> 05:01:21,960 MIGHT BE THE UNDERLYING REASON 8310 05:01:21,960 --> 05:01:24,960 WHY SOME INDIVIDUALS WITH THE 8311 05:01:24,960 --> 05:01:26,960 PLAQUES THE POSITIONS THEY DON'T 8312 05:01:26,960 --> 05:01:28,480 DEVELOP THE COGNITIVE 8313 05:01:28,480 --> 05:01:30,600 DYSFUNCTION AND SOME DO? 8314 05:01:30,600 --> 05:01:32,800 >> WHAT A GREAT QUESTION. 8315 05:01:32,800 --> 05:01:37,520 I SAW IT AND I SAID WHAT A GREAT 8316 05:01:37,520 --> 05:01:38,000 QUESTION. 8317 05:01:38,000 --> 05:01:40,520 THERE ARE DATA SHOWING WHEN YOU 8318 05:01:40,520 --> 05:01:43,280 REALLY BLOCK, THEY HAVE ANOTHER 8319 05:01:43,280 --> 05:01:44,840 TECHNIQUE THEY DO BASE DINE AND 8320 05:01:44,840 --> 05:01:48,120 THE SYSTEM IS FAILING. 8321 05:01:48,120 --> 05:01:49,920 THEY HAVE BEEN REPORTING 8322 05:01:49,920 --> 05:01:51,440 COGNITIVE CHANGES WITH THAT SO 8323 05:01:51,440 --> 05:01:56,600 YES, I MEAN, THERE MIGHT BE A 8324 05:01:56,600 --> 05:01:58,360 LINK BETWEEN COGNITIVE DECLINE 8325 05:01:58,360 --> 05:02:00,840 AND BEING ABLE TO DRAIN AND THAT 8326 05:02:00,840 --> 05:02:03,680 COULD BE ANATOMICAL VARIATIONS 8327 05:02:03,680 --> 05:02:07,120 AND CLEARLY, I MEAN, IT'S A 8328 05:02:07,120 --> 05:02:08,840 GREAT QUESTION. 8329 05:02:08,840 --> 05:02:09,240 THANK YOU. 8330 05:02:09,240 --> 05:02:09,720 >> GREAT. 8331 05:02:09,720 --> 05:02:11,400 THANK YOU SO MUCH. 8332 05:02:11,400 --> 05:02:13,080 I'LL LET BABAK, BECAUSE THE 8333 05:02:13,080 --> 05:02:14,520 CHAIR DUTIES ASK THE FINAL 8334 05:02:14,520 --> 05:02:15,880 QUESTION IF YOU CAN DO IT 8335 05:02:15,880 --> 05:02:17,240 QUICKLY AND WE'LL TAKE A BREAK 8336 05:02:17,240 --> 05:02:19,200 AND THE PANELISTS AND HOSTS CAN 8337 05:02:19,200 --> 05:02:20,320 ANSWER ANY REMAINING QUESTIONS 8338 05:02:20,320 --> 05:02:23,720 IN THE CHAT. 8339 05:02:23,720 --> 05:02:26,040 >> REALLY BEAUTIFUL 8340 05:02:26,040 --> 05:02:26,960 PRESENTATIONS. 8341 05:02:26,960 --> 05:02:28,760 HOW DO WE DISSEMINATE THESE 8342 05:02:28,760 --> 05:02:30,400 ABILITY TO DID THESE IMAGING? 8343 05:02:30,400 --> 05:02:35,200 THEY'RE NOT WIDELY AVAILABLE AND 8344 05:02:35,200 --> 05:02:37,200 GETTING LYMPH ANGIO GRAMS IS 8345 05:02:37,200 --> 05:02:38,800 VERY DIFFERENT AND THEY'RE HARD 8346 05:02:38,800 --> 05:02:39,120 TO INTERPRET. 8347 05:02:39,120 --> 05:02:42,360 HOW DO WE OVERCOME THAT PROBLEM? 8348 05:02:42,360 --> 05:02:46,640 >> YOU MEAN, HOW TO SPREAD THE 8349 05:02:46,640 --> 05:02:48,880 TECHNOLOGY OR TECHNIQUE OR HOW 8350 05:02:48,880 --> 05:02:49,080 TO -- 8351 05:02:49,080 --> 05:02:53,960 >> WE CAN'T REALLY, IT'S VERY 8352 05:02:53,960 --> 05:02:59,880 VARIABLE GETTING ANGIO GRAMS AND 8353 05:02:59,880 --> 05:03:00,720 SOMETIMES UNINTERPRETABLE. 8354 05:03:00,720 --> 05:03:05,480 HOW DO WE DO THAT MORE IN MORE 8355 05:03:05,480 --> 05:03:06,480 RADIOLOGY PROGRAMS. 8356 05:03:06,480 --> 05:03:10,200 >> YOU HAVE TO FIND THE PILLS 8357 05:03:10,200 --> 05:03:13,080 BUT IT IS INTERESTING TO THAT 8358 05:03:13,080 --> 05:03:17,440 AND EVERY PLACE I WORK WITH, 8359 05:03:17,440 --> 05:03:20,680 SOMEONE WANTS TO DO THAT AND 8360 05:03:20,680 --> 05:03:24,120 IT'S DIFFICULT TO SET UP BECAUSE 8361 05:03:24,120 --> 05:03:30,720 OF COMMENT PLECOMPLEXITY OF MRIE 8362 05:03:30,720 --> 05:03:34,280 REALLY EASY SO THAT'S WHAT I 8363 05:03:34,280 --> 05:03:35,760 STARTED TO SEE DIFFERENT PARTS 8364 05:03:35,760 --> 05:03:38,160 OF THE WORLD WITH MRI ACCESS 8365 05:03:38,160 --> 05:03:40,880 LESS, THEY STARTED TO DO CT 8366 05:03:40,880 --> 05:03:46,000 GEOGRAPHY AND IT WOR AMAZINGLY . 8367 05:03:46,000 --> 05:03:48,320 THE ONLY THING IS THE RADIATION 8368 05:03:48,320 --> 05:03:50,600 AND YOU COULDN'T GET AT THIS 8369 05:03:50,600 --> 05:03:53,680 MOMENT THE DYNAMIC INFORMATION 8370 05:03:53,680 --> 05:03:57,760 BUT REALLY JUST GET WHERE WE DID 8371 05:03:57,760 --> 05:04:01,000 ALL THE TECHNIQUE WHERE WE CAN 8372 05:04:01,000 --> 05:04:04,760 ACTUALLY PERFORM IT BASED ON CT 8373 05:04:04,760 --> 05:04:07,520 AND THAT WILL BE A BIG PROGRESS 8374 05:04:07,520 --> 05:04:09,600 BUT CT IS THE WAY TO GO FOR THE 8375 05:04:09,600 --> 05:04:11,040 SMALL PROGRAMS AND THE PEOPLE 8376 05:04:11,040 --> 05:04:14,600 THAT DON'T HAVE THE (INAUDIBLE). 8377 05:04:14,600 --> 05:04:18,680 >> THAT'S GOOD ADVISE. 8378 05:04:18,680 --> 05:04:26,080 >> IADVICE.COME AND LEARN, WE SE 8379 05:04:26,080 --> 05:04:27,760 PROGRAMS AROUND THE WORLD SO YOU 8380 05:04:27,760 --> 05:04:29,040 KNOW, IT'S TRUE THAT NOT EVERY 8381 05:04:29,040 --> 05:04:30,160 PLACE ON THE PLANT IS GOING TO 8382 05:04:30,160 --> 05:04:34,360 HAVE THE CAPACITY TO DO THAT BUT 8383 05:04:34,360 --> 05:04:36,720 AGAIN, THERE'S IN ORDER TO 8384 05:04:36,720 --> 05:04:37,680 UNDERSTAND THE WHOLE THING YOU 8385 05:04:37,680 --> 05:04:38,960 NEED TO UNDERSTAND THE FLOW AND 8386 05:04:38,960 --> 05:04:41,600 YOU NEED TO UNDERSTAND THE 8387 05:04:41,600 --> 05:04:41,880 DYNAMICS. 8388 05:04:41,880 --> 05:04:43,560 YOU NEED TO UNDERSTAND THE 8389 05:04:43,560 --> 05:04:45,360 ANATOMY. 8390 05:04:45,360 --> 05:04:46,600 THERE'S NO SUBSTITUTE. 8391 05:04:46,600 --> 05:04:49,200 CT IS OK FOR CERTAIN THINGS BUT 8392 05:04:49,200 --> 05:04:50,520 AMR CONTRAST IS THE BEST. 8393 05:04:50,520 --> 05:04:53,320 IT FLOWS MOST DISTAL' AND IT 8394 05:04:53,320 --> 05:04:55,160 WORKS WHEN IT'S DILUTED SO IT 8395 05:04:55,160 --> 05:05:03,280 SHOWS YOU EVERYTHING THE BEST. 8396 05:05:03,280 --> 05:05:04,880 CALL US, COME OVER AND LEARN HOW 8397 05:05:04,880 --> 05:05:05,640 TO DO IT. 8398 05:05:05,640 --> 05:05:07,000 IT'S NOT THAT COMPLICATED. 8399 05:05:07,000 --> 05:05:08,920 >> SOUNDS GOOD. 8400 05:05:08,920 --> 05:05:09,480 >> THANK YOU. 8401 05:05:09,480 --> 05:05:10,320 THANK YOU SO MUCH. 8402 05:05:10,320 --> 05:05:11,680 THANK YOU, GUYS. 8403 05:05:11,680 --> 05:05:13,280 SO, WE WILL TAKE A BREAK AFTER 8404 05:05:13,280 --> 05:05:14,680 REALLY EXCITING SESSION AND THE 8405 05:05:14,680 --> 05:05:15,840 LAST OF THE SYMPOSIUM AND THEN 8406 05:05:15,840 --> 05:05:18,240 WE'LL BE BACK HERE IN 10 MINUTES 8407 05:05:18,240 --> 05:05:20,760 AT 3:00 TO CLOSE OUT WITH A 8408 05:05:20,760 --> 05:05:22,400 SPECIAL SESSION SO THANK YOU 8409 05:05:22,400 --> 05:05:23,960 ALL. 8410 05:05:23,960 --> 05:05:24,320 COME BACK -- 8411 05:05:24,320 --> 05:05:26,800 >> WE'LL BE BACK AT 3:05. 8412 05:05:26,800 --> 05:05:28,840 WE EXTENDED TO GIVE YOU A CHANCE 8413 05:05:28,840 --> 05:05:30,000 FOR A FULL DISCUSSION. 8414 05:05:30,000 --> 05:05:31,440 >> THANK YOU SO MUCH. 8415 05:05:31,440 --> 05:05:32,520 SO 3:05. 8416 05:05:32,520 --> 05:05:34,040 SEE YOU IN A FEW MINUTES. 8417 05:05:34,040 --> 05:05:38,360 THANK YOU, ALL. 8418 05:05:38,360 --> 05:05:39,960 >>READY FOR THE LAST AND MOST 8419 05:05:39,960 --> 05:05:40,680 IMPORTANT SESSION. 8420 05:05:40,680 --> 05:05:41,960 PLEASE, TAKE IT AWAY. 8421 05:05:41,960 --> 05:05:44,800 >> GREAT. 8422 05:05:44,800 --> 05:05:45,640 THANK YOU. 8423 05:05:45,640 --> 05:05:49,480 THANK YOU FOR STAYING TO THE 8424 05:05:49,480 --> 05:05:49,680 END. 8425 05:05:49,680 --> 05:05:51,040 BABAK AND I PREPARED REMARKS 8426 05:05:51,040 --> 05:05:52,360 CLOSING OUT THE SESSION GRADES 8427 05:05:52,360 --> 05:05:54,640 ON THE GAPS AND OPPORTUNITIES 8428 05:05:54,640 --> 05:05:55,600 YOU PROVIDED. 8429 05:05:55,600 --> 05:05:56,960 OF THE LAST FEW DAYS HAVE 8430 05:05:56,960 --> 05:05:57,720 HIGHLIGHTED THE IMPORTANCE OF 8431 05:05:57,720 --> 05:05:58,760 THE LYMPHATIC SYSTEM AND HEALTH 8432 05:05:58,760 --> 05:05:59,600 AND DISEASE. 8433 05:05:59,600 --> 05:06:01,800 WE'VE BEEN IMPRESSED BY SCALE, 8434 05:06:01,800 --> 05:06:02,760 SPECIALIZATION, AND IMPORTANCE 8435 05:06:02,760 --> 05:06:04,920 FOR NORMAL PHYSIOLOGY AND 8436 05:06:04,920 --> 05:06:06,400 IMPLICATIONS AND A WIDE RANGE OF 8437 05:06:06,400 --> 05:06:08,640 DISEASES, DESPITE THE CHALLENGES 8438 05:06:08,640 --> 05:06:09,480 AHEAD, WE HAVE MANY REASONS TO 8439 05:06:09,480 --> 05:06:10,920 BE HOPEFUL FOR THE FUTURE OF 8440 05:06:10,920 --> 05:06:15,320 LYMPHATIC RESEARCH. 8441 05:06:15,320 --> 05:06:16,960 INVESTMENT IS THE NIH, THE 8442 05:06:16,960 --> 05:06:18,600 WORLD'S LARGEST FUNDER OF 8443 05:06:18,600 --> 05:06:19,680 BIOMEDICAL RESEARCH. 8444 05:06:19,680 --> 05:06:20,880 Dr. STEVEN JAMES THE DIRECTOR 8445 05:06:20,880 --> 05:06:23,880 OF DIVISION OF DIE JESS 8446 05:06:23,880 --> 05:06:25,520 ADVERTISE DISEASES AND DAVID GOV 8447 05:06:25,520 --> 05:06:28,240 FROM THE DIVISION OF SCIENCES 8448 05:06:28,240 --> 05:06:29,720 AND SHARED NIH'S VISION FOR 8449 05:06:29,720 --> 05:06:32,360 LYMPHATIC RESEARCH WITHIN NIDDK 8450 05:06:32,360 --> 05:06:40,840 AND NHLBI R RESPECTIVELY INCLUDG 8451 05:06:40,840 --> 05:06:43,440 THE LYMPHATIC RELATED RESEARCH 8452 05:06:43,440 --> 05:06:44,600 DISEASE RESEARCH CONDITION 8453 05:06:44,600 --> 05:06:46,520 DISEASE CATEGORIES. 8454 05:06:46,520 --> 05:06:48,240 Dr. RAILCAR DISCUSSED FUNDING 8455 05:06:48,240 --> 05:06:54,840 MECHANISMS TO EXCELERATE BENCH 8456 05:06:54,840 --> 05:06:55,280 TO BEDSIDE APPROACH. 8457 05:06:55,280 --> 05:06:56,640 AND INCLUDING THE CREATION OF 8458 05:06:56,640 --> 05:07:01,520 THE HUMAN BIO MOLECULAR ATLAS 8459 05:07:01,520 --> 05:07:02,720 PROGRAM, MEDICINE TASK WITH 8460 05:07:02,720 --> 05:07:04,040 MAPPING ALL CELLS AND TISSUES OF 8461 05:07:04,040 --> 05:07:06,120 THE HUMAN BODY WE'RE DELIGHTED 8462 05:07:06,120 --> 05:07:14,720 BY A NEW INITIATIVE AND FINALLY 8463 05:07:14,720 --> 05:07:16,960 SARENA THEY ESTABLISHED A 8464 05:07:16,960 --> 05:07:18,920 TRANS-NIH COORDINATING COMMITTEE 8465 05:07:18,920 --> 05:07:21,760 FROM MEMBERS OF 12 OF 27 NIH 8466 05:07:21,760 --> 05:07:23,440 INSTITUTES AND CENTERS FROM 8467 05:07:23,440 --> 05:07:24,360 REPRESENTATIVES FROM SEVERAL 8468 05:07:24,360 --> 05:07:26,800 PATIENT ADVOCACY GROUPS AS THE 8469 05:07:26,800 --> 05:07:29,240 AFRICAN PROVERB STATES, IF YOU 8470 05:07:29,240 --> 05:07:31,200 WANT TO RUN FAST RUN A GONE, IF 8471 05:07:31,200 --> 05:07:34,000 YOU WANT TO RUN FAR, RUN 8472 05:07:34,000 --> 05:07:34,280 TOGETHER. 8473 05:07:34,280 --> 05:07:36,000 WE ARE GRATEFUL FOR PATIENTS, 8474 05:07:36,000 --> 05:07:37,400 ADVOCATES, CLINICIANS 8475 05:07:37,400 --> 05:07:39,960 RESEARCHERS AND THE NIH FAMILY. 8476 05:07:39,960 --> 05:07:40,680 >> THANK YOU. 8477 05:07:40,680 --> 05:07:43,280 THIS WORKSHOP WAS DESIGNED TO 8478 05:07:43,280 --> 05:07:44,320 BRING TOGETHER BASIC 8479 05:07:44,320 --> 05:07:45,000 TRANSLATIONAL AND CLINICAL 8480 05:07:45,000 --> 05:07:46,400 EXPERTS TO PRESENT THE LATEST 8481 05:07:46,400 --> 05:07:48,600 ADVANCES IN THE FIELD AND ENGAGE 8482 05:07:48,600 --> 05:07:50,200 IN INTER DISCIPLINARY 8483 05:07:50,200 --> 05:07:50,640 DISCUSSIONS. 8484 05:07:50,640 --> 05:07:52,080 WE ASKED OUR SPEAKERS TO 8485 05:07:52,080 --> 05:07:54,120 IDENTIFY KNOWLEDGE GAPS AND 8486 05:07:54,120 --> 05:07:55,160 OPPORTUNITIES IN LYMPHATIC 8487 05:07:55,160 --> 05:07:55,760 RESEARCH. 8488 05:07:55,760 --> 05:07:57,640 OUR CONTRIBUTORS IDENTIFIED MANY 8489 05:07:57,640 --> 05:08:00,480 GAPS AND I'LL BROADLY SUMMARIZE 8490 05:08:00,480 --> 05:08:00,880 THESE. 8491 05:08:00,880 --> 05:08:02,600 EARLY DIAGNOSIS IS NUMBER ONE. 8492 05:08:02,600 --> 05:08:03,920 NUMBER WHO IS QUANTIFICATIONS OF 8493 05:08:03,920 --> 05:08:05,080 THE LYMPHATIC FUNCTION AND 8494 05:08:05,080 --> 05:08:06,480 EVALUATION OF LYMPHATIC AN AT 8495 05:08:06,480 --> 05:08:09,400 MAY AND NUMBER THREE IS 8496 05:08:09,400 --> 05:08:10,320 LYMPHATIC-SPECIFIC FARM CO 8497 05:08:10,320 --> 05:08:11,520 THERAPIES AND NUMBER FOUR IS 8498 05:08:11,520 --> 05:08:13,200 AVAILABLE ANIMAL MODELS AND I'LL 8499 05:08:13,200 --> 05:08:14,760 GO THROUGH SOME OF THESE IN 8500 05:08:14,760 --> 05:08:15,120 DETAIL. 8501 05:08:15,120 --> 05:08:16,640 ONE OF THE MOST FRUSTRATING 8502 05:08:16,640 --> 05:08:19,480 THINGS FOR PHYSICIAN AND 8503 05:08:19,480 --> 05:08:23,160 PATIENTS ARE NON-INVASIVE 8504 05:08:23,160 --> 05:08:24,720 DISEASE LEADING TO DELAYED 8505 05:08:24,720 --> 05:08:25,000 DIAGNOSIS. 8506 05:08:25,000 --> 05:08:29,320 WE DON'T HAVE ANY DRUGS THAT 8507 05:08:29,320 --> 05:08:30,760 IMPROVE LYMPHATIC FUNCTIONING 8508 05:08:30,760 --> 05:08:32,560 WITHOUT SIGNIFICANT OFF TARGET 8509 05:08:32,560 --> 05:08:32,880 EFFECTS. 8510 05:08:32,880 --> 05:08:35,840 ANIMAL MODELING INOF VARIOUS 8511 05:08:35,840 --> 05:08:39,360 DISEASES, KIDNEY DISEASE, LIVER 8512 05:08:39,360 --> 05:08:40,720 DISEASE AND OTHERS HAVE SHOWED 8513 05:08:40,720 --> 05:08:43,960 IMPROVING WITH VEGFC O OTHER 8514 05:08:43,960 --> 05:08:45,160 GROWTH FACTORS IS HELPFUL 8515 05:08:45,160 --> 05:08:47,080 HOWEVER THIS IS NOT CLINICALLY 8516 05:08:47,080 --> 05:08:47,840 TRANSLATABLE SINCE THESE 8517 05:08:47,840 --> 05:08:49,080 TREATMENTS CANNOT BE 8518 05:08:49,080 --> 05:08:55,400 ADMINISTERED LONG-TERM. 8519 05:08:55,400 --> 05:08:57,480 ANIMAL MODELS AND THERE'S AN 8520 05:08:57,480 --> 05:08:59,640 IMPORTANT NEED FOR LYMPHATIC 8521 05:08:59,640 --> 05:09:01,600 MUSCLE CELL SPECIFIC DRIVERS. 8522 05:09:01,600 --> 05:09:02,440 CROW DRIVERS. 8523 05:09:02,440 --> 05:09:03,600 THESE DRIVERS WOULD HELP US 8524 05:09:03,600 --> 05:09:06,240 UNDERSTAND WHY AND HOW LYMPHATIC 8525 05:09:06,240 --> 05:09:08,240 MUSCLE CELLS DEVELOP AND 8526 05:09:08,240 --> 05:09:08,680 REGENERATE. 8527 05:09:08,680 --> 05:09:11,760 IT'S IN MANY DISEASES SUCH AS 8528 05:09:11,760 --> 05:09:12,880 OBESITY AND THIS PROBLEM IS DUE 8529 05:09:12,880 --> 05:09:15,760 TO THE COMPLEXITY OF ACCURATELY 8530 05:09:15,760 --> 05:09:17,160 IMAGING LYMPHATIC VALUES IN VIVO 8531 05:09:17,160 --> 05:09:19,560 AS Dr. MICHAEL DAVIS NOTED, 8532 05:09:19,560 --> 05:09:20,760 VERY FEW STUD SEIZE HAVE BEEN 8533 05:09:20,760 --> 05:09:22,960 DONE ON HEALTHY HUMAN VESSELS TO 8534 05:09:22,960 --> 05:09:25,080 LOOK AT LYMPHATIC MUSCLE 8535 05:09:25,080 --> 05:09:26,600 FUNCTION AND MOST REALLY RELY ON 8536 05:09:26,600 --> 05:09:28,760 IN VITRO OR ANIMAL MODELS THAT 8537 05:09:28,760 --> 05:09:29,960 LACK GRAPH STATIONAL LOADS THAT 8538 05:09:29,960 --> 05:09:31,600 ARE PRESENT IN HUMAN LIMBS. 8539 05:09:31,600 --> 05:09:33,720 TECHNICAL DIFFICULTIES IN STUDY 8540 05:09:33,720 --> 05:09:35,040 THE HUMAN LYMPHATICS WITH MUSCLE 8541 05:09:35,040 --> 05:09:36,640 CELLS HAVE RESULTED IN ABUNDANCE 8542 05:09:36,640 --> 05:09:40,400 OF WORK IN LYMPHATIC AND CELLS 8543 05:09:40,400 --> 05:09:42,480 AND DIVERSE FUNCTION OF 8544 05:09:42,480 --> 05:09:44,040 LYMPHATIC MUSCLE CELLS. 8545 05:09:44,040 --> 05:09:46,400 A LOT OF THESE LINES, IT'S CLEAR 8546 05:09:46,400 --> 05:09:48,000 THAT DEVELOPING METHODS FOR 8547 05:09:48,000 --> 05:09:49,000 LYMPHATIC FUNCTION IS IMPORTANT 8548 05:09:49,000 --> 05:09:52,440 USING ADVANCED IMAGING, SODIUM 8549 05:09:52,440 --> 05:09:54,120 MRI AND OTHER TECHNIQUES IS 8550 05:09:54,120 --> 05:09:55,520 PROMISING AND I THINK 8551 05:09:55,520 --> 05:09:58,360 TRANSLATING THIS PRACTICE TO FOR 8552 05:09:58,360 --> 05:09:59,880 PATIENTS AND DISSEMINATING THIS 8553 05:09:59,880 --> 05:10:02,800 TECHNIQUES WIDELY IS IMPORTANT. 8554 05:10:02,800 --> 05:10:04,080 Dr. NICHOLS, IDENTIFIED GAPS 8555 05:10:04,080 --> 05:10:06,160 IN CONNECTING VARIOUS PATHOLOGIC 8556 05:10:06,160 --> 05:10:07,240 PROCESSES THAT HAVE BEEN 8557 05:10:07,240 --> 05:10:14,880 IDENTIFIED SUCH AS INFLAMMAT 8558 05:10:14,880 --> 05:10:16,400 INFLAMMATION -- THE NEED FOR MOE 8559 05:10:16,400 --> 05:10:17,880 LYMPHATIC CENTERS OF EXCELLENCE, 8560 05:10:17,880 --> 05:10:19,480 SPECIALIZED TRAINING FOR MEDICAL 8561 05:10:19,480 --> 05:10:20,920 STAFF AND TREATMENT OF IMAGING 8562 05:10:20,920 --> 05:10:23,920 OF LYMPHATIC DISORDERS, CREATIVE 8563 05:10:23,920 --> 05:10:26,080 APPROACHES SUCH AS STATE OF THE 8564 05:10:26,080 --> 05:10:27,760 ARTERY SEARCH AND CENTERS FOR 8565 05:10:27,760 --> 05:10:29,560 CHILDREN AND ADULT PATIENTS. 8566 05:10:29,560 --> 05:10:30,560 WE HAVE HEARD EXCITING REPORTS 8567 05:10:30,560 --> 05:10:32,320 ABOUT THE BASELINE DIFFERENCES 8568 05:10:32,320 --> 05:10:33,760 IN LYMPHATIC ANATOMY AND THE 8569 05:10:33,760 --> 05:10:35,040 EFFECT OF THE DIFFERENCES ON THE 8570 05:10:35,040 --> 05:10:36,960 RISK OF DEVELOPMENT. 8571 05:10:36,960 --> 05:10:38,800 FUTURE EXPERIMENTS TO HERM TO 8572 05:10:38,800 --> 05:10:42,280 YOU THEY MAY CONTRIBUTE TO LOWER 8573 05:10:42,280 --> 05:10:43,000 EXTREMITY. 8574 05:10:43,000 --> 05:10:44,880 THERE'S SCALE TRIALS ANALYZING 8575 05:10:44,880 --> 05:10:46,240 OUTCOMES WITH THE GOAL OF 8576 05:10:46,240 --> 05:10:49,280 DEFINING OPTIMAL SURGICAL CAL 8577 05:10:49,280 --> 05:10:51,800 ALGORITHM AND ANIZING THESE 8578 05:10:51,800 --> 05:10:52,840 OUTCOMES LONG-TERM. 8579 05:10:52,840 --> 05:10:55,480 THEY'RE NEEDED FOR INFLUENCE 8580 05:10:55,480 --> 05:10:56,880 COVERAGE AND HAVE TOX SIT TEE 8581 05:10:56,880 --> 05:10:58,520 FOR OUR PATIENTS AND THERE'S A 8582 05:10:58,520 --> 05:11:01,120 MAJOR NEED TO DETERMINE THE 8583 05:11:01,120 --> 05:11:02,760 PREVALENCE OF LYMPHATIC DISEASES 8584 05:11:02,760 --> 05:11:04,280 ALONG WITH INCREASED PHYSICIAN 8585 05:11:04,280 --> 05:11:05,680 EDUCATION AND PSYCHOSOCIAL 8586 05:11:05,680 --> 05:11:06,840 COUNSELING FOR PATIENTS WITH 8587 05:11:06,840 --> 05:11:08,520 LYMPHATIC DISORDERS AT THESE 8588 05:11:08,520 --> 05:11:10,960 DISEASES HAVE BEEN NEGLECTED. 8589 05:11:10,960 --> 05:11:14,160 >> THANK YOU SO MUCH, BABAK, FOR 8590 05:11:14,160 --> 05:11:16,120 OUTLINING THE MANY CLINICAL 8591 05:11:16,120 --> 05:11:16,600 CHALLENGES. 8592 05:11:16,600 --> 05:11:18,040 I'D LIKE TO DISCUSS THE 8593 05:11:18,040 --> 05:11:19,680 LIMITATIONS AND OBSTACLES WE 8594 05:11:19,680 --> 05:11:21,480 FACE AS BASIC RESEARCHERS. 8595 05:11:21,480 --> 05:11:22,680 A POPULAR THEME THROUGHOUT THE 8596 05:11:22,680 --> 05:11:25,160 WORKSHOP WAS THE HETEROGENEITY 8597 05:11:25,160 --> 05:11:26,200 OF LYMPHATIC AND CELLS 8598 05:11:26,200 --> 05:11:28,120 THROUGHOUT THE BODY. 8599 05:11:28,120 --> 05:11:30,120 Dr. OLIVER STONE DISCUSSED THE 8600 05:11:30,120 --> 05:11:31,680 DIVERSE ORIGINS AND THEIR 8601 05:11:31,680 --> 05:11:33,680 CONTRIBUTION TO ORGAN-SPECIFIC 8602 05:11:33,680 --> 05:11:33,960 PROGRAMS. 8603 05:11:33,960 --> 05:11:36,240 OUR SESSION 3 SPEAKERS FOCUSED 8604 05:11:36,240 --> 05:11:39,360 ON LYMPHATIC SYSTEM OF THE GI 8605 05:11:39,360 --> 05:11:46,400 TRACT AND METABOLICS DISORDER. 8606 05:11:46,400 --> 05:11:54,560 DR. SEUSS THE SYDNEY AND JOINT R 8607 05:11:54,560 --> 05:11:56,280 HEART AND BRAIN. 8608 05:11:56,280 --> 05:11:57,280 BEYOND SPECIALIZATION OF THE 8609 05:11:57,280 --> 05:12:00,600 LYMPHATIC SYSTEM, THERE WAS WORK 8610 05:12:00,600 --> 05:12:02,600 IDENTIFYING BOTH METABOLIC AND 8611 05:12:02,600 --> 05:12:06,080 IMMUNE LOGICAL DIVERSIFICATION 8612 05:12:06,080 --> 05:12:07,040 AND LYMPH NODES FROM THE PART OF 8613 05:12:07,040 --> 05:12:08,600 THE GUT AND DEMONSTRATED 8614 05:12:08,600 --> 05:12:09,960 DIFFERENCES IN THE LENGTH AND 8615 05:12:09,960 --> 05:12:11,000 STRUCTURE OF THE LYMPHATICS 8616 05:12:11,000 --> 05:12:12,600 ACROSS THE SMALL INTESTINE. 8617 05:12:12,600 --> 05:12:15,680 IN SUMMARY, THE LYMPHATIC SYSTEM 8618 05:12:15,680 --> 05:12:18,960 SPECIALIZED ACROSS ORGANS AND 8619 05:12:18,960 --> 05:12:19,640 WITHIN TISSUES. 8620 05:12:19,640 --> 05:12:20,680 BEYOND THE DIVERSIFICATION OF 8621 05:12:20,680 --> 05:12:22,080 THE LYMPHATIC SYSTEM WE LEARNED 8622 05:12:22,080 --> 05:12:27,280 ABOUT THE DISTINCT NICHE FROM 8623 05:12:27,280 --> 05:12:29,280 Dr. NATASHA, MICHAEL DAVIS, 8624 05:12:29,280 --> 05:12:32,480 RACHEL NICK AND DARIA. 8625 05:12:32,480 --> 05:12:33,920 OUR GREAT OF THE CHALLENGES ARE 8626 05:12:33,920 --> 05:12:35,080 DEVELOPING TOOLS AND 8627 05:12:35,080 --> 05:12:39,000 TECHNOLOGIES TO ACCURATELY 8628 05:12:39,000 --> 05:12:39,960 PROFILE LYMPHATIC PETTER OWE 8629 05:12:39,960 --> 05:12:47,640 -- AND DEVELOPING TRANSAGAIN IE 8630 05:12:47,640 --> 05:12:49,400 THESE POPULATIONS IN VIVO. 8631 05:12:49,400 --> 05:12:51,040 BACK TO YOU, BABAK. 8632 05:12:51,040 --> 05:12:52,640 >> ALTHOUGH WE IDENTIFIED MANY 8633 05:12:52,640 --> 05:12:54,440 GAPS AND DEFICIENCIES IN OUR 8634 05:12:54,440 --> 05:12:56,120 UNDERSTANDING OF THE LYMPHATIC 8635 05:12:56,120 --> 05:12:58,120 DISORDERS, THERE'S REASONS FOR 8636 05:12:58,120 --> 05:12:58,400 OPTIMISM. 8637 05:12:58,400 --> 05:12:59,280 INTEREST IN LYMPHATIC DISORDERS 8638 05:12:59,280 --> 05:13:01,080 IS AN ALL-TIME HIGH AND MORE 8639 05:13:01,080 --> 05:13:08,240 BRIGHT AND YOUNG INVESTIGATORS 8640 05:13:08,240 --> 05:13:14,720 AND THEY WILL DEDEASE THE BURDEN 8641 05:13:14,720 --> 05:13:16,800 OF THIS DISEASE FOR OUR 8642 05:13:16,800 --> 05:13:17,440 PATIENTS. 8643 05:13:17,440 --> 05:13:18,840 INCREASING OUR UNDERSTANDING OF 8644 05:13:18,840 --> 05:13:20,600 LYMPHATIC ANATOMY MAY DECREASE 8645 05:13:20,600 --> 05:13:24,920 THE RISK OF DEVELOPING 8646 05:13:24,920 --> 05:13:25,880 LYMPHATIC. 8647 05:13:25,880 --> 05:13:27,200 DEVELOPMENTS OF SURGICAL 8648 05:13:27,200 --> 05:13:28,840 TECHNIQUES AND COMBINATION OF 8649 05:13:28,840 --> 05:13:30,640 MEDICAL THERAPY TO IMPROVE WILL 8650 05:13:30,640 --> 05:13:31,840 HELP TREAT PATIENTS WITH 8651 05:13:31,840 --> 05:13:33,240 LYMPHATIC DISORDERS. 8652 05:13:33,240 --> 05:13:34,560 DECREASE COST OF TOOLS AND 8653 05:13:34,560 --> 05:13:37,720 SCREENING WILL HELP US IMPROVE 8654 05:13:37,720 --> 05:13:39,120 OUR LYMPHATIC DISEASES AND LEAD 8655 05:13:39,120 --> 05:13:41,320 TO BETTER TREATMENT AND EARLIER 8656 05:13:41,320 --> 05:13:44,520 DIAGNOSIS OF LYMPHATIC MALL 8657 05:13:44,520 --> 05:13:45,480 FORMATIONS, LIP EDEMA AND OTHER 8658 05:13:45,480 --> 05:13:46,680 DISORDERS AND THIS INCREASED 8659 05:13:46,680 --> 05:13:49,280 UNDERSTAND OF WILL UNDOUBTEDLY 8660 05:13:49,280 --> 05:13:50,960 LEAD TARGETED TREATMENTS 8661 05:13:50,960 --> 05:13:51,760 IDENTIFYING THE GAPS IN OUR 8662 05:13:51,760 --> 05:13:52,800 KNOWLEDGE IS THE FIRST STEP 8663 05:13:52,800 --> 05:13:54,600 TOWARDS THIS GOAL AND IT WILL 8664 05:13:54,600 --> 05:13:55,280 LEAD TO BREAK THROUGHS AND 8665 05:13:55,280 --> 05:13:56,560 INCREASE FUNDING FOR LYMPHATIC 8666 05:13:56,560 --> 05:13:58,200 RESEARCH WILL INCREASE OUR 8667 05:13:58,200 --> 05:14:01,040 KNOWLEDGE BASED AND EFFECTIVE 8668 05:14:01,040 --> 05:14:01,320 TEACHINGS. 8669 05:14:01,320 --> 05:14:02,240 >> EXCELLENT. 8670 05:14:02,240 --> 05:14:04,280 WE'RE GETTING CLOSE, GUYS, THANK 8671 05:14:04,280 --> 05:14:04,560 YOU. 8672 05:14:04,560 --> 05:14:06,200 SO, DESPITE THE CHALLENGES 8673 05:14:06,200 --> 05:14:07,640 IDENTIFIED BY WORKSHOP 8674 05:14:07,640 --> 05:14:10,120 PARTICIPANTS, AND PATIENTS, AND 8675 05:14:10,120 --> 05:14:11,480 ADVOCATES, WE ARE HOPEFUL. 8676 05:14:11,480 --> 05:14:12,960 THANK YOU FOR BEING ENGAGING AND 8677 05:14:12,960 --> 05:14:14,840 THOUGHTFUL PARTICIPANTS. 8678 05:14:14,840 --> 05:14:21,520 OVER THE LAST TWO CARRYING OUR A 8679 05:14:21,520 --> 05:14:25,560 NOVEMBEREL MODEL FOR FORM -- AND 8680 05:14:25,560 --> 05:14:27,000 THE FIRST FROM. 8681 05:14:27,000 --> 05:14:29,120 Dr. JOSHUA SCALING DICE SECTED 8682 05:14:29,120 --> 05:14:34,080 THE AK SIS FOR BUT THE OBJECT BN 8683 05:14:34,080 --> 05:14:36,240 AND LEARNED ABOUT SPACIAL AND 8684 05:14:36,240 --> 05:14:38,600 ADVANCE DATA ANALYSIS TO 8685 05:14:38,600 --> 05:14:41,360 RECONSTRUCT THE ACCESS 8686 05:14:41,360 --> 05:14:42,920 FURTHERMORE OTHERS PRESENTED HE 8687 05:14:42,920 --> 05:14:49,200 WILL GENERAELEGANT WORK USING I. 8688 05:14:49,200 --> 05:14:50,720 THE INCREDIBLE PROGRESS WAS 8689 05:14:50,720 --> 05:14:53,560 SHARED BY THE HUMAN CELL ATLAS 8690 05:14:53,560 --> 05:14:55,440 CONSORTIUM TO MAP ALL CELLS OF 8691 05:14:55,440 --> 05:14:57,040 THE HUMAN BODY. 8692 05:14:57,040 --> 05:14:58,560 THE CONSTRUCTION OF AN ATLAS OF 8693 05:14:58,560 --> 05:15:02,480 THE VASCULARTURE CELLS AT THE 8694 05:15:02,480 --> 05:15:05,680 LYMPHATIC SYSTEM IS A GREAT 8695 05:15:05,680 --> 05:15:06,120 NEED. 8696 05:15:06,120 --> 05:15:07,720 Dr. GEHLENBORG SHOWED TOOLS 8697 05:15:07,720 --> 05:15:09,560 HIS TEAM DEVELOPED TO STUDY 8698 05:15:09,560 --> 05:15:11,840 MULTI SKILLED DATA AND THE 8699 05:15:11,840 --> 05:15:15,480 WEALTH OF DATA BY HUBMAP TO 8700 05:15:15,480 --> 05:15:17,080 IDENTIFY GENE AND PROTEIN 8701 05:15:17,080 --> 05:15:21,480 BIOMARKERS OF ORGAN SPECIFIC 8702 05:15:21,480 --> 05:15:22,560 LYMPHATIC CELLS. 8703 05:15:22,560 --> 05:15:24,680 >> OUR HOPE IS WE MADE SOME 8704 05:15:24,680 --> 05:15:25,000 INTRODUCTIONS. 8705 05:15:25,000 --> 05:15:26,440 AND INCREASE AWARENESS OF 8706 05:15:26,440 --> 05:15:27,760 LYMPHATIC DISORDERS. 8707 05:15:27,760 --> 05:15:30,120 WE NEED BROAD CROSS DISCIPLINARY 8708 05:15:30,120 --> 05:15:31,160 COLLABORATION TO SOLVE MAJOR 8709 05:15:31,160 --> 05:15:33,080 PROBLEMS THAT WE FACE AS 8710 05:15:33,080 --> 05:15:41,520 RESOU -->> LAST LASTLY, WE WANTE 8711 05:15:41,520 --> 05:15:43,280 BY EMPHASIZING THE NEED OF OPEN 8712 05:15:43,280 --> 05:15:45,040 SHARING FOR DATA, PROTOCOLS, 8713 05:15:45,040 --> 05:15:46,440 TRANSGENIC ANIMALS AND RESEARCH 8714 05:15:46,440 --> 05:15:47,640 FINDINGS TO ADVANCE THE FIELD. 8715 05:15:47,640 --> 05:15:49,280 A COMMITMENT TO OPEN SCIENCE AND 8716 05:15:49,280 --> 05:15:50,560 KNOWLEDGE DISSEMINATION IS KEY 8717 05:15:50,560 --> 05:15:52,360 TO IMPROVING ACCESS AND 8718 05:15:52,360 --> 05:15:53,360 DEVELOPING TREATMENTS FOR 8719 05:15:53,360 --> 05:15:54,720 LYMPHATIC DISORDERS. 8720 05:15:54,720 --> 05:15:56,920 WE ARE EMPOWERED BY HEARING 8721 05:15:56,920 --> 05:15:58,440 PATIENTS' STORIES AND BY YOUR 8722 05:15:58,440 --> 05:16:00,480 PASSION, CLARITY OF PURPOSE, AND 8723 05:16:00,480 --> 05:16:03,280 COMMITMENT TO BETTER CARE FOR 8724 05:16:03,280 --> 05:16:03,440 ALL. 8725 05:16:03,440 --> 05:16:04,560 >> THANK YOU AGAIN FOR YOUR 8726 05:16:04,560 --> 05:16:08,800 INTEREST AND ENTHUSIASM. 8727 05:16:08,800 --> 05:16:10,000 RESEARCH IS A TEAM SPORT. 8728 05:16:10,000 --> 05:16:12,000 WE HOPE THIS EVENT WILL FORGE 8729 05:16:12,000 --> 05:16:12,880 COLLABORATIVE PARTNERSHIPS AMONG 8730 05:16:12,880 --> 05:16:14,000 ALL OF YOU HERE. 8731 05:16:14,000 --> 05:16:15,040 AND WE HOPE THAT YOU HAVE A 8732 05:16:15,040 --> 05:16:16,240 GREAT DAY AND THANK YOU FOR 8733 05:16:16,240 --> 05:16:17,200 JOINING US TODAY. 8734 05:16:17,200 --> 05:16:20,160 I'M GOING TO TURN IT OVER FOR 8735 05:16:20,160 --> 05:16:20,880 FINAL REMARKS. 8736 05:16:20,880 --> 05:16:21,920 >> THANK YOU. 8737 05:16:21,920 --> 05:16:23,880 IT'S MY PRIVILEGE TO CLOSE THE 8738 05:16:23,880 --> 05:16:27,040 WORKSHOP AND HAVE A THANKS FOR 8739 05:16:27,040 --> 05:16:30,880 GRATITUDE TO EVERYONE WHO 8740 05:16:30,880 --> 05:16:33,480 CONTRIBUTED IN EVERY STEP OF 8741 05:16:33,480 --> 05:16:36,200 THIS WORKSHOP AS THE NIH 8742 05:16:36,200 --> 05:16:37,280 ORGANIZING COMMITTEE AND WE 8743 05:16:37,280 --> 05:16:39,520 WOULD LIKE TO THANK TO ALL NIH 8744 05:16:39,520 --> 05:16:41,400 MEMBERS AND PATIENTS ADVOCACY 8745 05:16:41,400 --> 05:16:44,360 GROUPS GUESTS OFF THE TRANS NIH 8746 05:16:44,360 --> 05:16:45,760 LYMPHATIC COORDINATION FOR THEIR 8747 05:16:45,760 --> 05:16:47,320 VALUABLE INPUT AND SUPPORT. 8748 05:16:47,320 --> 05:16:49,160 WE WOULD LIKE TO EXTEND OUR 8749 05:16:49,160 --> 05:16:52,840 SINCERE APPRECIATION TO GRAND 8750 05:16:52,840 --> 05:16:54,320 RANDOLPH FOR SHAPING THIS 8751 05:16:54,320 --> 05:16:55,880 WORKSHOP AND WE CAN'T THANK 8752 05:16:55,880 --> 05:17:00,840 ENOUGH TO ANDREA AND BABAK FOR 8753 05:17:00,840 --> 05:17:02,720 THEIR IMPORTANT CONTRIBUTION, 8754 05:17:02,720 --> 05:17:03,920 THEIR VISION, PASSION AND THEIR 8755 05:17:03,920 --> 05:17:06,320 HARD WORK TO MAKE THIS WORKSHOP 8756 05:17:06,320 --> 05:17:06,720 HAPPEN. 8757 05:17:06,720 --> 05:17:07,960 THEY COMMITTED MANY HOURS OF 8758 05:17:07,960 --> 05:17:09,000 THEIR BUSY TIMES. 8759 05:17:09,000 --> 05:17:12,200 THANK YOU SO MUCH AND ALL THESE 8760 05:17:12,200 --> 05:17:13,800 EFFORTS COMBINED WITH THE MOST 8761 05:17:13,800 --> 05:17:15,560 INTERESTING TALKS AND ENGAGING 8762 05:17:15,560 --> 05:17:18,280 DISCUSSIONS OF OUR SPEAKERS AND 8763 05:17:18,280 --> 05:17:19,600 MODERATORS WE LEARNED A LOT IN 8764 05:17:19,600 --> 05:17:21,360 THESE TWO DAYS. 8765 05:17:21,360 --> 05:17:25,720 WE CAN'T THANK YOU ENOUGH TO OUR 8766 05:17:25,720 --> 05:17:28,360 SPEAKERS TO INITIATE A BETTER 8767 05:17:28,360 --> 05:17:28,720 UNDERSTANDING. 8768 05:17:28,720 --> 05:17:31,000 HOW THEIR LIVES ARE EFFECTED IN 8769 05:17:31,000 --> 05:17:32,800 MANY LEVELS AND THEY HIGHLIGHTED 8770 05:17:32,800 --> 05:17:35,720 THE NEEDS OF THE COMMUNITY TO 8771 05:17:35,720 --> 05:17:37,520 COMPLIMENT THE RESEARCH WITH THE 8772 05:17:37,520 --> 05:17:41,160 PATIENTS EXPERIENCES, IT'S VERY 8773 05:17:41,160 --> 05:17:41,400 VALUABLE. 8774 05:17:41,400 --> 05:17:42,880 THANK YOU ALL FOR THE CONSULTING 8775 05:17:42,880 --> 05:17:46,080 GROUP FOR THE SUPPORT AS AS WELL 8776 05:17:46,080 --> 05:17:48,080 AS THE NIH MEDIA CAST TEAM FOR 8777 05:17:48,080 --> 05:17:48,920 THIS VIRTUAL EVENT. 8778 05:17:48,920 --> 05:17:50,040 IT MAGICALLY HAPPENS. 8779 05:17:50,040 --> 05:17:54,000 THANK YOU SO MUCH FOR THAT. 8780 05:17:54,000 --> 05:17:56,440 AND ALSO, WE WOULD LIKE TO 8781 05:17:56,440 --> 05:18:00,360 EXTEND OUR SPECIAL THANKS TO 8782 05:18:00,360 --> 05:18:01,000 SERENA. 8783 05:18:01,000 --> 05:18:04,880 I'M REALLY THANKFUL FOR HER 8784 05:18:04,880 --> 05:18:06,960 MENTORSHIP ALSO AND SHE IS THE 8785 05:18:06,960 --> 05:18:09,200 ONE WHO SPEARHEADED THIS YET TO 8786 05:18:09,200 --> 05:18:10,920 BE CHARTED SEMINARS AND SHE 8787 05:18:10,920 --> 05:18:13,480 CONTINUES TO SHARE HER VISION TO 8788 05:18:13,480 --> 05:18:17,560 MOVE THE FIELD FORWARD. 8789 05:18:17,560 --> 05:18:18,240 THANK YOU. 8790 05:18:18,240 --> 05:18:21,360 AND WE HOPE THAT THIS WORKSHOP 8791 05:18:21,360 --> 05:18:22,600 REACHED ITS GOAL TO INFORM ALL 8792 05:18:22,600 --> 05:18:24,880 OF US ABOUT THE LATEST ADVANCES 8793 05:18:24,880 --> 05:18:26,560 IN LYMPHATIC RESEARCH AND 8794 05:18:26,560 --> 05:18:30,360 PROVIDED A PLATFORM FOR THE 8795 05:18:30,360 --> 05:18:31,840 THOUGHT PROVOKING DISCUSSIONS 8796 05:18:31,840 --> 05:18:33,640 AND LAST BUT NOT LEAST, WE WOULD 8797 05:18:33,640 --> 05:18:35,520 LIKE TO THANK YOU FOR LISTENING 8798 05:18:35,520 --> 05:18:36,880 AND JOINING IN THE DISCUSSIONS 8799 05:18:36,880 --> 05:18:39,200 OF THIS WORKSHOP AND WE HOPE WE 8800 05:18:39,200 --> 05:18:41,800 GAVE A GOOD OFF LINE FOR THE 8801 05:18:41,800 --> 05:18:42,760 OPPORTUNITIES IN LYMPHATIC 8802 05:18:42,760 --> 05:18:43,960 RESEARCH WHICH WE SHOULD WORK 8803 05:18:43,960 --> 05:18:45,680 ALL TOGETHER TO ADVANCE THIS 8804 05:18:45,680 --> 05:18:47,280 FIELD AND FINALLY, WE ARE ENDING 8805 05:18:47,280 --> 05:18:52,480 WITH A HOPEFUL NOTE ECHOING 8806 05:18:52,480 --> 05:18:54,000 ANDREA AND BABAK'S NOTE THAT 8807 05:18:54,000 --> 05:18:55,600 THERE'S ALREADY A GREAT 8808 05:18:55,600 --> 05:18:57,200 LYMPHATIC COMMUNITY AND WE WILL 8809 05:18:57,200 --> 05:18:59,520 WORK TO MAKE IT BETTER AND WE 8810 05:18:59,520 --> 05:19:00,760 ARE READY TO TAKE THE EFFORTS TO 8811 05:19:00,760 --> 05:19:02,800 IN THE NEXT LEVEL TO PROVIDE 8812 05:19:02,800 --> 05:19:04,440 HELP AND HOPE TO MAKE THE LIVES 8813 05:19:04,440 --> 05:19:06,400 OF THE PEOPLE WITH LYMPHATIC 8814 05:19:06,400 --> 05:19:07,120 DISEASES BETTER. 8815 05:19:07,120 --> 05:19:12,720 I HOPE YOU HAVE A GO GOOD VERY D 8816 05:19:12,720 --> 05:19:12,960 EVENING. 8817 05:19:12,960 --> 05:19:13,640 >> THANK YOU, EVERYONE. 8818 05:19:13,640 --> 05:19:23,880 >> THANK YOU.