1 00:00:00,330 --> 00:00:01,009 (Transcribed by TurboScribe - Upgrade to Unlimited to remove this message.) Slide please, Gaetano. 2 00:00:01,910 --> 00:00:04,670 All right, and now we are back to 3 00:00:04,670 --> 00:00:08,010 our main speakers for today. 4 00:00:08,270 --> 00:00:10,410 Again, as I mentioned at the beginning, our 5 00:00:10,410 --> 00:00:16,430 incredible fellow team, they all have a number 6 00:00:16,430 --> 00:00:19,310 of projects ongoing and have been presenting all 7 00:00:19,310 --> 00:00:20,570 around the country and the world. 8 00:00:21,070 --> 00:00:23,030 So we get to hear some of their 9 00:00:23,030 --> 00:00:25,250 recent work that was presented at the CNS. 10 00:00:25,510 --> 00:00:28,170 And Gaetano, I think you're going to be 11 00:00:28,170 --> 00:00:29,290 going first, is that correct? 12 00:00:31,650 --> 00:00:32,010 Yes, sir. 13 00:00:32,970 --> 00:00:42,230 All right, let me share my screen. 14 00:00:58,430 --> 00:00:59,950 All right, good morning everyone. 15 00:01:00,530 --> 00:01:02,850 So today I'll be presenting on our initial 16 00:01:02,850 --> 00:01:06,170 results of precision treatment of postoperative CSF leaks 17 00:01:06,170 --> 00:01:08,950 with ultrasound-guided epidural blood patch. 18 00:01:09,210 --> 00:01:10,650 And this is a talk that I gave 19 00:01:10,650 --> 00:01:12,970 us in our presentation at CNS in Austin 20 00:01:12,970 --> 00:01:15,030 and really was the work of the entire 21 00:01:15,030 --> 00:01:17,330 spine team here at Mayo Clinic Florida, as 22 00:01:17,330 --> 00:01:19,430 well as Dr. Clendan and James West. 23 00:01:24,190 --> 00:01:26,250 I don't have any disclosures relevant to this 24 00:01:26,250 --> 00:01:26,550 talk. 25 00:01:27,350 --> 00:01:29,690 And as you know, incidental durotomy is a 26 00:01:29,690 --> 00:01:31,710 very well-known complication of spine surgery. 27 00:01:32,050 --> 00:01:34,070 And if left untreated, it can lead to 28 00:01:34,070 --> 00:01:36,730 a persistent CSF leak or a pseudomeningocele. 29 00:01:37,190 --> 00:01:39,950 The reported rate of incidental durotomy ranges from 30 00:01:39,950 --> 00:01:42,490 4% to 16%, depending on the index 31 00:01:42,490 --> 00:01:43,070 operation. 32 00:01:43,750 --> 00:01:47,090 And if patients develop symptoms of persistent CSF 33 00:01:47,090 --> 00:01:49,190 leak, first-line treatment is bedrest. 34 00:01:49,710 --> 00:01:51,990 Other options include over-sewing the wound and 35 00:01:51,990 --> 00:01:53,290 placement of a lumbar drain. 36 00:01:53,810 --> 00:01:55,710 And there is the potential need of having 37 00:01:55,710 --> 00:01:57,750 to go back to the OR for direct 38 00:01:57,750 --> 00:01:58,210 repair. 39 00:02:00,370 --> 00:02:03,450 While epidural blood patches are routinely used to 40 00:02:03,450 --> 00:02:06,810 treat post-anesthesia or post-LP CSF leaks, 41 00:02:06,890 --> 00:02:09,470 they are not often used after spine surgery 42 00:02:09,470 --> 00:02:10,950 for durotomy repair. 43 00:02:11,310 --> 00:02:13,290 The problem is that the ultrasound is a 44 00:02:13,290 --> 00:02:15,890 great technique that allows radiation-free and direct 45 00:02:15,890 --> 00:02:18,590 real-time visualization of the pseudomeningocele, the dura, 46 00:02:18,730 --> 00:02:19,510 and the toy needle. 47 00:02:19,890 --> 00:02:22,370 But this application in the native spine is 48 00:02:22,370 --> 00:02:23,350 often very limited. 49 00:02:24,010 --> 00:02:26,890 That's magnified in the post-operative spine, thanks 50 00:02:26,890 --> 00:02:28,830 to the bone work that has been done 51 00:02:28,830 --> 00:02:31,450 by removing the bony anatomy and the ligaments 52 00:02:31,450 --> 00:02:34,110 there, which allows a window for the ultrasound 53 00:02:34,110 --> 00:02:36,470 and for the needle to be visualized properly. 54 00:02:37,970 --> 00:02:40,430 So in our study, we did a retrospective 55 00:02:40,430 --> 00:02:43,250 analysis of patients underwent the USCBP at Mayo 56 00:02:43,250 --> 00:02:47,230 Clinic, Florida, from 2009 to 2020 for symptomatic 57 00:02:47,230 --> 00:02:49,930 pseudomeningocele secondary to spine surgery. 58 00:02:50,250 --> 00:02:53,710 We collected demographic, procedural, and outcome characteristics. 59 00:02:54,490 --> 00:02:56,870 The primary outcome of our study was ultrasound 60 00:02:56,870 --> 00:03:00,030 EBP success, defined as a resolution of the 61 00:03:00,030 --> 00:03:03,210 initial symptom that brought the pseudomeningocele to clinical 62 00:03:03,210 --> 00:03:06,510 attention, such as postural headaches, incisional leak. 63 00:03:08,590 --> 00:03:11,130 So for our technique, patients are position-prone. 64 00:03:11,550 --> 00:03:14,490 The ultrasound is used to localize the pseudomeningocele, 65 00:03:14,870 --> 00:03:17,110 and the color doppler can also be adopted 66 00:03:17,110 --> 00:03:19,290 to determine if there are any active sites 67 00:03:19,290 --> 00:03:21,470 of CSF leak of ingression. 68 00:03:22,290 --> 00:03:25,430 Under ultrasound guidance, an 18-gauge toy needle 69 00:03:25,430 --> 00:03:28,270 is advanced into the pseudomeningocele, and the content 70 00:03:28,270 --> 00:03:29,170 is aspirated. 71 00:03:30,050 --> 00:03:31,870 The needle is then advanced into the epidural 72 00:03:31,870 --> 00:03:34,850 space, and about 30 ml of autologous blood 73 00:03:34,850 --> 00:03:38,290 is injected epidurally in 5-10 ml aliquots 74 00:03:38,290 --> 00:03:40,350 under continuous ultrasound guidance. 75 00:03:41,190 --> 00:03:43,370 Then after waiting for 5-10 minutes to 76 00:03:43,370 --> 00:03:46,190 allow the blood patch to sit, the ultrasound 77 00:03:46,190 --> 00:03:48,230 is then used again to confirm the placement 78 00:03:48,230 --> 00:03:50,530 of the patch, and the color doppler can 79 00:03:50,530 --> 00:03:52,530 also be used to confirm an absence of 80 00:03:52,530 --> 00:03:55,410 CSF regress if that was previously identified. 81 00:03:56,810 --> 00:04:00,090 So overall, we had 48 patients who underwent 82 00:04:00,090 --> 00:04:03,530 a total of 61 USCBPs, and you can 83 00:04:03,530 --> 00:04:06,370 see that the most frequent index operation was 84 00:04:06,370 --> 00:04:10,950 a laminectomy, 24.5%, and about 36.7 85 00:04:10,950 --> 00:04:14,510 % of these cases were revision surgeries, and 86 00:04:14,510 --> 00:04:17,709 also that the incident of derotomy was unrecognized 87 00:04:17,709 --> 00:04:20,310 during the surgery in about 22% of 88 00:04:20,310 --> 00:04:20,709 cases. 89 00:04:25,620 --> 00:04:27,580 You can see here that the median time 90 00:04:27,580 --> 00:04:30,180 from surgery to symptom development was 7 days, 91 00:04:30,540 --> 00:04:33,900 and the most frequent symptoms of representation were 92 00:04:33,900 --> 00:04:37,260 postural headaches in 64% of cases and 93 00:04:37,260 --> 00:04:40,220 incisional leak in 26.5% of cases. 94 00:04:41,540 --> 00:04:44,480 Here, looking at the results of the EBP 95 00:04:44,480 --> 00:04:46,960 under ultrasound guidance, you can see that 51 96 00:04:46,960 --> 00:04:49,900 % of patients experienced resolution of their symptom 97 00:04:49,900 --> 00:04:52,960 after their first blood patch, and you can 98 00:04:52,960 --> 00:04:55,120 see that the median volume aspirated from the 99 00:04:55,120 --> 00:04:59,140 pseudomeningocele was 34 ml, and also that another 100 00:04:59,140 --> 00:05:02,860 20% of patients experienced resolution of their 101 00:05:02,860 --> 00:05:05,860 symptom after subsequent attempts of blood patches. 102 00:05:08,600 --> 00:05:10,020 We're talking about complication. 103 00:05:10,240 --> 00:05:13,360 We had about 14% complication in our 104 00:05:13,360 --> 00:05:15,580 series, and the most frequent one was wound 105 00:05:15,580 --> 00:05:18,500 infection in two patients, followed by meningitis also 106 00:05:18,500 --> 00:05:19,300 in two patients. 107 00:05:21,690 --> 00:05:23,390 Here is a couple of illustrative cases. 108 00:05:23,590 --> 00:05:25,210 You can see here a patient that presented 109 00:05:25,210 --> 00:05:28,030 with the dura laevi fistula, and here on 110 00:05:28,030 --> 00:05:30,170 the t2-sagittal MRI, you can see a 111 00:05:30,170 --> 00:05:33,930 fairly large pseudomeningocele after the patient had undergone 112 00:05:33,930 --> 00:05:36,430 the laminectomies and obliteration of the EBP fistula, 113 00:05:36,910 --> 00:05:38,970 and then the patient underwent an ultrasound, a 114 00:05:38,970 --> 00:05:39,850 bit of a blood patch. 115 00:05:39,950 --> 00:05:42,550 The contents of the pseudomeningocele was aspirated and 116 00:05:42,550 --> 00:05:44,570 a blood patch placed, and then you can 117 00:05:44,570 --> 00:05:47,010 see on the postoperative MRI, sagittal and axial 118 00:05:47,010 --> 00:05:49,270 cut that was done one month after the 119 00:05:49,270 --> 00:05:52,310 procedure, complete resolution of the pseudomeningocele. 120 00:05:54,700 --> 00:05:56,520 This is another case of a patient that 121 00:05:56,520 --> 00:05:58,340 laminectomy, as you can see here on the 122 00:05:58,340 --> 00:06:00,540 CT scan, on the level above a previous 123 00:06:00,540 --> 00:06:03,960 fusion construct, and there is an hypodensity there 124 00:06:03,960 --> 00:06:06,560 of a fluid collection that was also again 125 00:06:06,560 --> 00:06:08,760 identified under the ultrasound where you can see 126 00:06:08,760 --> 00:06:11,160 the star there, and then the color Doppler 127 00:06:11,160 --> 00:06:13,780 was used to identify the active CSF regression 128 00:06:13,780 --> 00:06:14,100 there. 129 00:06:14,980 --> 00:06:16,700 The 2A needle, you can see here in 130 00:06:16,700 --> 00:06:19,200 white where this big arrow is, is inserted. 131 00:06:19,420 --> 00:06:21,640 The contents of the pseudomeningocele is aspirated, as 132 00:06:21,640 --> 00:06:23,640 you can see in figure E, and then 133 00:06:23,640 --> 00:06:26,260 the blood patch is placed, and this is 134 00:06:26,260 --> 00:06:28,840 a postoperative scan that documents resolution of the 135 00:06:28,840 --> 00:06:29,680 pseudomeningocele. 136 00:06:30,760 --> 00:06:33,200 So, our study carries all the limitations of 137 00:06:33,200 --> 00:06:35,520 all single institutional retrospective studies. 138 00:06:35,980 --> 00:06:38,800 Therefore, further prospective and multi-centered studies are 139 00:06:38,800 --> 00:06:42,380 needed to confirm the generalizability of our data, 140 00:06:42,660 --> 00:06:44,940 but our study is the first in the 141 00:06:44,940 --> 00:06:48,120 largest series describing the adoption of US EBP 142 00:06:48,120 --> 00:06:52,560 in patients presenting with persistent pseudomeningocele and CSF 143 00:06:52,560 --> 00:06:54,080 leak following spine surgery. 144 00:06:54,380 --> 00:06:56,920 We found an overall success rate of over 145 00:06:56,920 --> 00:07:00,060 70% with a first attempt success rate 146 00:07:00,060 --> 00:07:01,640 of 50%. 147 00:07:01,640 --> 00:07:03,920 So, this suggests that the utilization of US 148 00:07:03,920 --> 00:07:06,720 -guided EBP in expert hand may allow for 149 00:07:06,720 --> 00:07:09,760 targeted treatment of a large portion of symptomatic 150 00:07:09,760 --> 00:07:11,800 postoperative pseudomeningoceles. 151 00:07:12,420 --> 00:07:13,320 Thank you. 152 00:07:17,560 --> 00:07:19,180 Gattano, that's excellent work. 153 00:07:19,300 --> 00:07:19,960 Congratulations. 154 00:07:21,080 --> 00:07:24,320 That's a novel treatment for these non-uncommon 155 00:07:24,320 --> 00:07:24,760 problems. 156 00:07:25,280 --> 00:07:26,860 One thing that, you know, I realized I 157 00:07:26,860 --> 00:07:29,820 never asked Dr. Miller or Dr. Clendenin, what's 158 00:07:29,820 --> 00:07:32,860 the consistency of the blood that you're using 159 00:07:32,860 --> 00:07:34,520 as the patch, and how long is it 160 00:07:34,520 --> 00:07:37,880 in between obtaining the autologous blood and actually 161 00:07:37,880 --> 00:07:38,640 injecting it? 162 00:07:40,970 --> 00:07:43,130 I don't know about the time between the 163 00:07:43,130 --> 00:07:46,190 when the blood is drawn and injected, sir, 164 00:07:46,190 --> 00:07:48,310 but most of them, I believe it may 165 00:07:48,310 --> 00:07:50,350 have been done at the same time of 166 00:07:50,350 --> 00:07:51,310 the procedure, sir. 167 00:07:51,910 --> 00:07:54,510 Yeah, but I mean, they aspirate it and 168 00:07:54,510 --> 00:07:56,810 then immediately give it, you know, I was 169 00:07:56,810 --> 00:07:58,410 just curious about how thick the blood is. 170 00:07:58,550 --> 00:08:01,890 Maybe, Elliard, I see Dr. Brahasi. 171 00:08:02,670 --> 00:08:05,290 Yeah, I do some of these as well. 172 00:08:05,490 --> 00:08:05,730 Okay. 173 00:08:05,910 --> 00:08:07,910 And yeah, we go right away for the 174 00:08:07,910 --> 00:08:09,510 blood, you know, so it's right from an 175 00:08:09,510 --> 00:08:11,710 IV catheter to the epidural space. 176 00:08:12,010 --> 00:08:13,810 But you know, what's really helpful is the 177 00:08:13,810 --> 00:08:14,850 Tissiel fibrin glue. 178 00:08:15,250 --> 00:08:16,930 So it's like in our, you know, human 179 00:08:16,930 --> 00:08:20,510 fibrin blood components that we inject, and that 180 00:08:20,510 --> 00:08:23,450 solidifies much, much quicker, and it's much more 181 00:08:23,450 --> 00:08:23,830 firm. 182 00:08:24,030 --> 00:08:25,750 So, you know, with the blood, it's thinner 183 00:08:25,750 --> 00:08:28,130 and can get into different crevices, while the 184 00:08:28,130 --> 00:08:29,770 fibrin glue is a bit more firm. 185 00:08:29,830 --> 00:08:31,190 So you try to get both properties in 186 00:08:31,190 --> 00:08:32,010 there right at the leak. 187 00:08:33,010 --> 00:08:33,330 Excellent. 188 00:08:33,490 --> 00:08:34,049 Yeah, thanks. 189 00:08:34,070 --> 00:08:34,549 Thanks, Tien. 190 00:08:34,570 --> 00:08:35,270 I appreciate that. 191 00:08:35,429 --> 00:08:37,190 Elliard, did you want to give us your 192 00:08:37,190 --> 00:08:37,730 hand up there? 193 00:08:37,770 --> 00:08:38,850 Do you want to make a comment? 194 00:08:40,210 --> 00:08:41,210 Yeah, yeah. 195 00:08:41,210 --> 00:08:43,150 Sorry, I can't join on camera because I'm 196 00:08:43,150 --> 00:08:46,370 tied up in the hospital. 197 00:08:47,610 --> 00:08:51,310 But I would like to second those comments. 198 00:08:51,430 --> 00:08:52,910 I've done this couple of cases with Dr. 199 00:08:52,950 --> 00:08:54,290 Quinden, and a lot of times what we 200 00:08:54,290 --> 00:08:56,010 do is we place an arterial line, so 201 00:08:56,010 --> 00:08:58,050 that way we can reliably draw blood right 202 00:08:58,050 --> 00:09:02,350 away as soon as access is identified with 203 00:09:02,350 --> 00:09:03,190 the ultrasound machine. 204 00:09:04,070 --> 00:09:06,090 And yeah, fibrin glue has also been something 205 00:09:06,090 --> 00:09:08,830 new that's been very helpful for this case. 206 00:09:09,830 --> 00:09:12,330 One question that I had, and it's something 207 00:09:12,330 --> 00:09:14,830 that we always worry about, is the risk 208 00:09:14,830 --> 00:09:16,650 of infection and meningitis. 209 00:09:17,070 --> 00:09:19,010 And it's interesting from the data presented, there 210 00:09:19,010 --> 00:09:20,450 was about two, I believe. 211 00:09:22,590 --> 00:09:25,290 Any thoughts on, you know, looking at the 212 00:09:25,290 --> 00:09:27,030 data, anything that we can do to make 213 00:09:27,030 --> 00:09:29,910 things better or reduce that risk? 214 00:09:29,910 --> 00:09:34,150 Or is this contributed directly to the block 215 00:09:34,150 --> 00:09:34,610 itself? 216 00:09:34,690 --> 00:09:36,730 Or was there other circumstances on those two 217 00:09:36,730 --> 00:09:38,390 patients that got infections? 218 00:09:39,090 --> 00:09:39,830 Thank you. 219 00:09:40,430 --> 00:09:41,150 Yes, sir. 220 00:09:41,250 --> 00:09:41,830 Excellent question. 221 00:09:41,870 --> 00:09:43,270 As you said, yeah, we had about two 222 00:09:43,270 --> 00:09:46,110 patients, about 4% for our series. 223 00:09:46,110 --> 00:09:48,430 It's a small series, so it's difficult to 224 00:09:48,430 --> 00:09:50,830 generalize if that's really a 4% for 225 00:09:50,830 --> 00:09:51,930 the procedure itself. 226 00:09:52,370 --> 00:09:54,170 But that was assumed to be related, was 227 00:09:54,170 --> 00:09:56,510 meningitis assumed to be related to the procedure, 228 00:09:56,750 --> 00:09:58,930 not like a UTI or any other infections. 229 00:10:06,130 --> 00:10:11,390 And let's see, we have a question from 230 00:10:11,390 --> 00:10:14,470 Dr. Vargas about what about the presence of 231 00:10:14,470 --> 00:10:16,730 fibrous tissue after the procedure? 232 00:10:17,110 --> 00:10:18,010 And I think... 233 00:10:18,010 --> 00:10:20,810 Yeah, so these are usually done like, scar, 234 00:10:20,970 --> 00:10:21,550 that sort of thing. 235 00:10:22,390 --> 00:10:25,050 Yeah, so these are usually done right after 236 00:10:25,050 --> 00:10:26,350 the procedure. 237 00:10:26,490 --> 00:10:27,190 It's not too long. 238 00:10:27,290 --> 00:10:29,030 And that's why it's very difficult to do 239 00:10:29,030 --> 00:10:30,270 them anatomically guided. 240 00:10:30,650 --> 00:10:33,310 That's why the ultrasound really helps to visualize 241 00:10:33,310 --> 00:10:33,970 the anatomy. 242 00:10:34,490 --> 00:10:35,770 And as far as we didn't have any 243 00:10:35,770 --> 00:10:38,090 issues as far as going through fibrous tissue 244 00:10:38,090 --> 00:10:39,370 or the patches. 245 00:10:41,810 --> 00:10:42,230 Great. 246 00:10:42,390 --> 00:10:44,530 Well, thank you so much, Gaetano. 247 00:10:46,430 --> 00:10:48,050 Yeah, a couple more points here. 248 00:10:48,130 --> 00:10:50,850 Dr. Dean mentioned would emphasize the need to 249 00:10:50,850 --> 00:10:52,430 make sure patient is a febrile and has 250 00:10:52,430 --> 00:10:54,930 normal white blood cell count prior to the 251 00:10:54,930 --> 00:10:55,550 blood patch. 252 00:10:55,810 --> 00:10:58,210 And I know that's part of the protocol 253 00:10:58,210 --> 00:10:59,430 and a good point. 254 00:10:59,530 --> 00:11:02,770 Some of these patients are immediate post-operative. 255 00:11:02,870 --> 00:11:04,910 They have an immediate post-operative status, so 256 00:11:04,910 --> 00:11:06,410 they might have an elevated white blood cell 257 00:11:06,410 --> 00:11:07,690 count just from surgery. 258 00:11:09,390 --> 00:11:11,470 But yeah, very, very good point. 259 00:11:12,770 --> 00:11:14,110 So, all right. 260 00:11:14,490 --> 00:11:16,090 So excellent work, Gaetano. 261 00:11:16,790 --> 00:11:18,810 And we will go on to the next 262 00:11:18,810 --> 00:11:19,530 presentation. 263 00:11:22,550 --> 00:11:25,490 We have Dr. Garcia, who's going to be 264 00:11:25,490 --> 00:11:27,270 presenting next. 265 00:11:28,330 --> 00:11:29,530 Can you see this, Dr. Fox? 266 00:11:30,170 --> 00:11:30,650 Yes. 267 00:11:31,870 --> 00:11:33,410 Oh, it's advancing by itself. 268 00:11:34,250 --> 00:11:34,690 All right. 269 00:11:34,930 --> 00:11:36,010 So morning, everyone. 270 00:11:36,270 --> 00:11:38,070 Today, I'm going to be presenting on SPECT 271 00:11:38,070 --> 00:11:40,070 -CT as a predictor of pain generators in 272 00:11:40,070 --> 00:11:43,090 patients undergoing inter-articulate injections for neck and 273 00:11:43,090 --> 00:11:43,590 back pain. 274 00:11:44,010 --> 00:11:45,990 I think most of you already know of 275 00:11:45,990 --> 00:11:46,490 this project. 276 00:11:46,550 --> 00:11:47,870 It's a project that we did with the 277 00:11:47,870 --> 00:11:49,950 spine group and on the particular mentorship of 278 00:11:49,950 --> 00:11:50,790 Dr. Oboriyama. 279 00:11:51,150 --> 00:11:53,550 And we presented it at Austin at the 280 00:11:53,550 --> 00:11:54,870 Congress of Neurological Surgeons. 281 00:11:55,190 --> 00:11:57,330 So, as you know, low back pain and 282 00:11:57,330 --> 00:11:58,690 also neck pain, but there's a lot more 283 00:11:58,690 --> 00:12:00,550 literature on low back pain, is one of 284 00:12:00,550 --> 00:12:04,390 the main leading causes of disability in general. 285 00:12:04,870 --> 00:12:07,650 And yet, the identification of painful generators is 286 00:12:07,650 --> 00:12:12,190 still difficult, despite the use of multiple morphological 287 00:12:12,190 --> 00:12:16,270 -based studies, including x-ray, CT, MRI, and 288 00:12:16,270 --> 00:12:18,590 also compounded by the fact that sometimes structural 289 00:12:18,590 --> 00:12:20,890 abnormalities that are found on the scans have 290 00:12:20,890 --> 00:12:23,570 no direct correlation with the actual pain of 291 00:12:23,570 --> 00:12:26,150 the patient, which makes the correct identification of 292 00:12:26,150 --> 00:12:27,690 the painful generator difficult. 293 00:12:28,050 --> 00:12:30,730 And therefore, the targeted treatment for that painful 294 00:12:30,730 --> 00:12:32,970 generator also difficult and limited. 295 00:12:32,970 --> 00:12:35,490 With this in mind, there have been some 296 00:12:35,490 --> 00:12:39,610 interest in functional-based tests, like SPECT, to 297 00:12:39,610 --> 00:12:42,270 accurately identify those painful generators. 298 00:12:43,370 --> 00:12:46,030 More recently, a scan has been developed, which 299 00:12:46,030 --> 00:12:48,950 is called the hybrid SPECT-CT, which at 300 00:12:48,950 --> 00:12:51,470 Mayo we have been fortunate to have available 301 00:12:51,470 --> 00:12:53,170 for a number of years and with good 302 00:12:53,170 --> 00:12:54,650 quality, as I'm going to show in one 303 00:12:54,650 --> 00:12:55,710 of the example scans. 304 00:12:56,210 --> 00:12:58,390 So, the idea here was to look at 305 00:12:58,390 --> 00:13:01,990 facet joint injections, targeted injections, and see whether 306 00:13:01,990 --> 00:13:05,850 or not the hypothesis that injections targeted at 307 00:13:05,850 --> 00:13:09,070 positive sites of uptake would do better than 308 00:13:09,070 --> 00:13:11,410 injections targeted at foci without uptake. 309 00:13:11,950 --> 00:13:13,870 So, to accomplish this, we designed a study 310 00:13:13,870 --> 00:13:16,590 with a single institution retrospective, in which we 311 00:13:16,590 --> 00:13:19,590 compared both short and long-term outcomes for 312 00:13:19,590 --> 00:13:22,190 patients undergoing facet joint injections for neck and 313 00:13:22,190 --> 00:13:22,750 back pain. 314 00:13:23,510 --> 00:13:25,430 Given the large sample size, I was able 315 00:13:25,430 --> 00:13:27,350 to do a propensity score match to adjust 316 00:13:27,350 --> 00:13:30,690 for age, gender, BMI, hypertension, and multiple target 317 00:13:30,690 --> 00:13:32,350 injections and injection location. 318 00:13:32,830 --> 00:13:36,750 We did exclude sacroiliac joint injections, given that 319 00:13:36,750 --> 00:13:38,150 they are a bit different and they should 320 00:13:38,150 --> 00:13:41,510 not be grouped all the same with cervical, 321 00:13:41,750 --> 00:13:43,270 thoracic, and lumbar injections. 322 00:13:43,830 --> 00:13:45,350 So, these were our main outcomes. 323 00:13:45,490 --> 00:13:48,730 We looked at immediate positive response, change in 324 00:13:48,730 --> 00:13:52,410 VAS two weeks after injection, improvement in VAS 325 00:13:52,410 --> 00:13:55,470 above 50 and 70 percent after injection, and 326 00:13:55,470 --> 00:13:58,090 need for additional treatment, both injection and surgery. 327 00:13:58,850 --> 00:14:01,830 Importantly, at Mayo, we have people who do 328 00:14:01,830 --> 00:14:04,750 call these patients two weeks after the procedure 329 00:14:04,750 --> 00:14:07,190 who are not implicated in the research. 330 00:14:07,410 --> 00:14:09,870 So, they're able to give us an unbiased 331 00:14:09,870 --> 00:14:12,530 feedback from the patient regarding patient report outcomes, 332 00:14:12,610 --> 00:14:15,930 which allowed us to really objectify these outcomes. 333 00:14:16,390 --> 00:14:17,770 So, as you can see, we have a 334 00:14:17,770 --> 00:14:21,450 large number of patients, 2,849 patients that 335 00:14:21,450 --> 00:14:24,570 were evaluated with SPECT-CT within five years. 336 00:14:24,690 --> 00:14:27,950 Out of these ones, we had 340 with 337 00:14:27,950 --> 00:14:30,710 facet injections within 150 days after SPECT-CT. 338 00:14:31,230 --> 00:14:32,270 Why 150 days? 339 00:14:32,270 --> 00:14:33,370 We had to choose a threshold. 340 00:14:33,790 --> 00:14:37,490 There is no specific literature on the threshold. 341 00:14:37,610 --> 00:14:38,890 We just had to come up with a 342 00:14:38,890 --> 00:14:40,890 threshold that would allow us to look at 343 00:14:40,890 --> 00:14:44,070 outcomes that were associated with injection, not associated 344 00:14:44,070 --> 00:14:46,150 with something else that could have happened in 345 00:14:46,150 --> 00:14:46,730 the interlude. 346 00:14:47,130 --> 00:14:49,930 So, we had a total of 140 cervical 347 00:14:49,930 --> 00:14:53,890 injections, 21 thoracic injections, and 207 lumbar injections. 348 00:14:54,590 --> 00:14:58,450 Importantly, 265 were uptake-targeted injections. 349 00:14:58,570 --> 00:15:00,110 By this, we mean that all the injections 350 00:15:00,110 --> 00:15:02,150 were targeted at facet of uptake, all of 351 00:15:02,150 --> 00:15:02,330 them. 352 00:15:02,410 --> 00:15:05,290 That was our definition of uptake-targeted injections, 353 00:15:05,370 --> 00:15:08,130 and 75 were non-uptake-targeted injections. 354 00:15:08,730 --> 00:15:09,910 So, as you can see here, just an 355 00:15:09,910 --> 00:15:12,810 example of a SPECT-CT at Mayo with, 356 00:15:13,230 --> 00:15:15,690 in this particular patient, a right L4-L5 357 00:15:15,690 --> 00:15:19,170 facet joint having uptake that was targeted by 358 00:15:19,170 --> 00:15:19,590 injections. 359 00:15:19,650 --> 00:15:21,550 This is actually one of the cases that 360 00:15:21,550 --> 00:15:22,630 was included in the study. 361 00:15:23,110 --> 00:15:25,590 So, here are just some demographics and characteristics 362 00:15:25,590 --> 00:15:28,210 of the location and characteristics of the injection. 363 00:15:28,690 --> 00:15:29,850 As you can see, even though there is 364 00:15:29,850 --> 00:15:33,090 nothing that is statistically significant, it can always 365 00:15:33,090 --> 00:15:35,830 compound and have a confounding effect on the 366 00:15:35,830 --> 00:15:38,410 variables, hence why we did the propensity score 367 00:15:38,410 --> 00:15:41,010 match to adjust for all these variables. 368 00:15:41,590 --> 00:15:43,930 What you can see here is that both 369 00:15:43,930 --> 00:15:46,870 on a univariable analysis and a multivariable analysis, 370 00:15:46,870 --> 00:15:51,550 we did not find statistically significant differences between 371 00:15:51,550 --> 00:15:54,930 non-uptake and uptake- targeted injections, but 372 00:15:54,930 --> 00:15:56,990 when we did look at patients who already 373 00:15:56,990 --> 00:15:59,330 had a failed injection before the SPECT-CT 374 00:15:59,330 --> 00:16:02,470 and in which the surgeon or procedurist was 375 00:16:02,470 --> 00:16:04,590 able to change the target based on the 376 00:16:04,590 --> 00:16:07,190 information of the SPECT-CT, here below, what 377 00:16:07,190 --> 00:16:08,790 you can see is that in those patients, 378 00:16:08,870 --> 00:16:10,810 we do have a benefit, and the benefit 379 00:16:10,810 --> 00:16:13,410 was particularly greater if there was any change 380 00:16:13,410 --> 00:16:14,350 made on the target. 381 00:16:14,910 --> 00:16:17,290 So, that is very suggestive that for a 382 00:16:17,290 --> 00:16:20,630 particular set of patients with adequate patient selection, 383 00:16:20,810 --> 00:16:22,630 you do see a benefit with SPECT-CT 384 00:16:22,630 --> 00:16:25,250 to guide facet-trained injections. 385 00:16:25,990 --> 00:16:30,250 So, basically, our conclusions seem to support that 386 00:16:30,250 --> 00:16:34,050 pending adequate patient selection, SPECT-CT has a 387 00:16:34,050 --> 00:16:37,110 benefit in guiding facet injections. 388 00:16:37,710 --> 00:16:39,750 There are limitations, of course, with our retrospective 389 00:16:39,750 --> 00:16:42,010 single institution study, but we did use a 390 00:16:42,010 --> 00:16:44,010 propensity score to match for confounding variables. 391 00:16:44,150 --> 00:16:46,250 We have a large sample size, but of 392 00:16:46,250 --> 00:16:50,070 course, future directions would have to be prospective, 393 00:16:50,610 --> 00:16:54,350 multi-side, hopefully, double-blind clinical trial to 394 00:16:54,350 --> 00:16:57,870 accurately discern the impact of SPECT-CT in 395 00:16:57,870 --> 00:16:59,070 routine clinical practice. 396 00:16:59,890 --> 00:17:00,890 And I'll take any questions. 397 00:17:08,119 --> 00:17:09,099 Excellent, Diogo. 398 00:17:09,380 --> 00:17:13,180 Really fabulous work, and I think this is, 399 00:17:14,420 --> 00:17:17,440 you know, there's so much potential applicability to 400 00:17:17,440 --> 00:17:22,440 using imaging biomarkers for better delineating patients' pain. 401 00:17:23,839 --> 00:17:25,599 You know, in this, you know, even with 402 00:17:25,599 --> 00:17:30,260 the precision of these SPECT studies, it shows 403 00:17:30,260 --> 00:17:33,060 how challenging it can be to figure out 404 00:17:33,060 --> 00:17:36,400 pain generators in the spine, and I think 405 00:17:36,400 --> 00:17:38,020 this is incredible work with a lot of 406 00:17:38,020 --> 00:17:38,500 promise. 407 00:17:39,140 --> 00:17:42,000 Based on what you've seen so far, who 408 00:17:42,000 --> 00:17:44,120 do you think, I mean, we should be 409 00:17:44,120 --> 00:17:45,740 doing this more or less, or do you 410 00:17:45,740 --> 00:17:48,000 think people should have this up front? 411 00:17:48,100 --> 00:17:50,360 I mean, how do you recommend we use 412 00:17:50,360 --> 00:17:52,240 this based on your knowledge of the technique 413 00:17:52,240 --> 00:17:53,460 in our everyday practice? 414 00:17:54,220 --> 00:17:56,520 So, the patients that I did see have 415 00:17:56,520 --> 00:17:58,420 a benefit were patients in which there had 416 00:17:58,420 --> 00:18:00,800 already been an attempt at an injection. 417 00:18:01,180 --> 00:18:03,520 So, because my understanding is that SPECT-CT 418 00:18:03,520 --> 00:18:06,820 is sensitive, but not necessarily specific, so it's 419 00:18:06,820 --> 00:18:09,380 difficult to figure out which of those facets 420 00:18:09,380 --> 00:18:10,900 that are lighting up are the ones that 421 00:18:10,900 --> 00:18:12,540 are actually causing pain. 422 00:18:12,660 --> 00:18:14,160 So, when we have the benefit of having 423 00:18:14,160 --> 00:18:15,860 a patient that already had a procedure that 424 00:18:15,860 --> 00:18:18,400 failed, we do know which of those joints 425 00:18:18,400 --> 00:18:20,600 did light it up, but they're not the 426 00:18:20,600 --> 00:18:22,580 actual painful generator, so we can take those 427 00:18:22,580 --> 00:18:24,180 out and pursue the next ones. 428 00:18:24,580 --> 00:18:26,380 So, I do see SPECT-CT not as 429 00:18:26,380 --> 00:18:28,840 a necessary first line for any patient that 430 00:18:28,840 --> 00:18:31,520 has a first procedure, but for a recurrent 431 00:18:31,520 --> 00:18:33,660 facet injection, for a patient who has not 432 00:18:33,660 --> 00:18:35,700 benefited from a facet injection, I would definitely 433 00:18:35,700 --> 00:18:36,640 see benefit there. 434 00:18:36,700 --> 00:18:39,140 But, of course, I think to actually make 435 00:18:39,140 --> 00:18:41,400 a recommendation, we would have to have a 436 00:18:41,400 --> 00:18:43,760 double-blind clinical trial so we can make 437 00:18:43,760 --> 00:18:44,400 a recommendation. 438 00:18:45,420 --> 00:18:46,240 Hopefully coming. 439 00:18:47,240 --> 00:18:47,880 Hopefully so. 440 00:18:48,360 --> 00:18:50,520 Yeah, and we'll continue to learn more about 441 00:18:50,520 --> 00:18:52,340 these imaging biomarkers, which I think will be 442 00:18:52,340 --> 00:18:52,940 very helpful. 443 00:18:53,480 --> 00:18:54,960 Dr. Dean makes a great point in the 444 00:18:54,960 --> 00:18:57,260 comments as well that we have extremely high 445 00:18:57,260 --> 00:19:00,000 -quality SPECT studies at Mayo, which, you know, 446 00:19:00,060 --> 00:19:01,200 I completely agree. 447 00:19:01,380 --> 00:19:03,060 At UF, we didn't do this at all, 448 00:19:03,180 --> 00:19:05,940 so this was something novel to me seeing 449 00:19:05,940 --> 00:19:08,440 here, and I'm very impressed with the quality 450 00:19:08,440 --> 00:19:09,180 of these studies. 451 00:19:09,500 --> 00:19:11,300 So, excellent work. 452 00:19:12,180 --> 00:19:14,180 All right, I think we can move on 453 00:19:14,180 --> 00:19:16,940 now to our next presentation. 454 00:19:18,220 --> 00:19:21,460 Dr. Vivas Butrago, who is going to be 455 00:19:21,460 --> 00:19:25,660 speaking about supermarginal resection impact on overall survival 456 00:19:25,660 --> 00:19:27,960 for IDH wild-type glioblastoma. 457 00:19:29,360 --> 00:19:30,240 Perfect, sir. 458 00:19:30,260 --> 00:19:30,960 Can you hear me now? 459 00:19:31,660 --> 00:19:32,040 Yes. 460 00:19:32,500 --> 00:19:33,140 Yes, thank you. 461 00:19:33,460 --> 00:19:36,540 Let me share the screen here. 462 00:19:38,440 --> 00:19:38,800 All right. 463 00:19:38,920 --> 00:19:39,780 Are you seeing my slide? 464 00:19:40,760 --> 00:19:41,120 Yes. 465 00:19:42,000 --> 00:19:42,560 Perfect. 466 00:19:47,540 --> 00:19:48,460 Good morning, everyone. 467 00:19:48,580 --> 00:19:50,700 Thank you for attending this lecture today. 468 00:19:51,900 --> 00:19:54,900 So, I'm going to present our study that 469 00:19:54,900 --> 00:19:57,640 we presented in October this year in CNS. 470 00:19:58,340 --> 00:20:00,460 The title of this study is supermarginal resection 471 00:20:00,460 --> 00:20:03,020 impact on overall survival for IDH wild-type 472 00:20:03,020 --> 00:20:05,840 glioblastoma according to their cell density distribution and 473 00:20:05,840 --> 00:20:06,660 infiltration profile. 474 00:20:07,100 --> 00:20:08,520 This is a mathematical model. 475 00:20:11,710 --> 00:20:14,050 So, we have no disclosures for this lecture. 476 00:20:14,710 --> 00:20:16,490 So, a bit of background regarding the extent 477 00:20:16,490 --> 00:20:17,750 of resection on glioblastoma. 478 00:20:18,970 --> 00:20:22,410 We know that not long ago, the most 479 00:20:22,410 --> 00:20:25,970 common surgical recommendation for glioblastoma was to perform 480 00:20:25,970 --> 00:20:28,530 only a biopsy, and this was not only 481 00:20:28,530 --> 00:20:29,970 in the United States but worldwide. 482 00:20:30,250 --> 00:20:34,670 But since the 2000s, we started seeing very 483 00:20:34,670 --> 00:20:39,790 important studies from Dr. LaCroix, from Dr. McGirt, 484 00:20:40,930 --> 00:20:44,810 from Dr. Sanai, from UCSF with Dr. Berger, 485 00:20:46,190 --> 00:20:49,150 and from Dr. Chaychana and Dr. Quinones with 486 00:20:49,150 --> 00:20:51,570 this data from Hopkins that all of these 487 00:20:51,570 --> 00:20:56,170 studies were in favor of performing more extensive 488 00:20:56,170 --> 00:21:01,510 surgical resection on patients with glioblastoma, and the 489 00:21:01,510 --> 00:21:05,690 results were pretty much homogeneous, identifying that resections 490 00:21:05,690 --> 00:21:09,790 above 78% of the contrast enhancement in 491 00:21:09,790 --> 00:21:16,230 T1 were associated with a significant improvement in 492 00:21:16,230 --> 00:21:18,390 overall survival in patients with GBM. 493 00:21:20,540 --> 00:21:24,060 But furthermore, we see that the gross total 494 00:21:24,060 --> 00:21:30,840 resection is this complete surgical resection of the 495 00:21:30,840 --> 00:21:34,520 contrast enhancement component of the tumor that you 496 00:21:34,520 --> 00:21:35,380 can see up here. 497 00:21:35,840 --> 00:21:39,080 But what about the flare component in the 498 00:21:39,080 --> 00:21:40,060 T2 sequence? 499 00:21:40,460 --> 00:21:43,380 We have known for a while already that 500 00:21:43,380 --> 00:21:47,060 there are infiltrated GBM cells within the brain 501 00:21:47,060 --> 00:21:51,200 tissue that most of the time is not 502 00:21:51,200 --> 00:21:55,900 being taken care of or resected because of 503 00:21:55,900 --> 00:22:02,980 the infiltrated behavior of these cells within functional 504 00:22:02,980 --> 00:22:05,520 brain tissue that if you resected it, you 505 00:22:05,520 --> 00:22:08,780 can cause a deficit in the functionality of 506 00:22:08,780 --> 00:22:09,200 the patient. 507 00:22:09,940 --> 00:22:12,820 So we end with our group at Mayo 508 00:22:12,820 --> 00:22:15,720 Clinic to start looking at the extent of 509 00:22:15,720 --> 00:22:18,820 the supermarginal resection beyond the margins of the 510 00:22:18,820 --> 00:22:21,040 contrast enhancement tumor. 511 00:22:21,620 --> 00:22:24,340 And we have seen that regarding this topic 512 00:22:24,340 --> 00:22:28,060 that it has been influenced by the results 513 00:22:28,060 --> 00:22:33,940 from the good results from extended resection beyond 514 00:22:33,940 --> 00:22:37,160 the margins in lower gliomas. 515 00:22:37,320 --> 00:22:39,460 We see here the very important papers from 516 00:22:39,460 --> 00:22:44,980 MD Anderson, from Hopkins, from Cleveland Clinic, and 517 00:22:44,980 --> 00:22:45,900 from UCSF. 518 00:22:46,600 --> 00:22:50,700 And not all of them have homogeneous results 519 00:22:50,700 --> 00:22:55,080 as we found before in the gross total 520 00:22:55,080 --> 00:22:58,840 resection for the T1 contrast. 521 00:22:59,500 --> 00:23:00,840 So we wanted to give it a shot. 522 00:23:01,320 --> 00:23:05,620 And thanks to all the data that we 523 00:23:05,620 --> 00:23:07,880 have at Mayo Clinic with the high flow 524 00:23:07,880 --> 00:23:12,300 of patients, we were able to do this 525 00:23:12,300 --> 00:23:15,940 study in which we identified more than 800 526 00:23:15,940 --> 00:23:16,660 patients. 527 00:23:16,920 --> 00:23:19,560 And we selected only those patients that were 528 00:23:19,560 --> 00:23:20,840 IDH mutants. 529 00:23:20,920 --> 00:23:23,240 This is the most aggressive type of GBM 530 00:23:23,730 --> 00:23:27,780 that has a less overall survival in total. 531 00:23:28,160 --> 00:23:31,860 So we only selected those patients that had 532 00:23:31,860 --> 00:23:36,280 a gross total resection of the contrast enhancement, 533 00:23:36,780 --> 00:23:40,280 and that they did present before the surgery 534 00:23:40,280 --> 00:23:44,200 with some degree of preoperative flare. 535 00:23:44,760 --> 00:23:47,800 So in total, we included 101 patients. 536 00:23:48,440 --> 00:23:52,500 We performed all volumetric analysis on all the 537 00:23:52,500 --> 00:23:56,740 sequences in the contrast enhancement, in the necrosis 538 00:23:56,740 --> 00:23:58,860 part, and in the flare for all the 539 00:23:58,860 --> 00:23:59,320 patients. 540 00:24:00,880 --> 00:24:03,200 And we did find in the univariate and 541 00:24:03,200 --> 00:24:07,860 multivariate analysis that increasing SMR as it continues 542 00:24:07,860 --> 00:24:09,580 viral for the first time, we can show 543 00:24:09,580 --> 00:24:14,100 that is statistically significant for an increase and 544 00:24:14,100 --> 00:24:17,900 improved overall survival in our patient population. 545 00:24:18,580 --> 00:24:21,380 And furthermore, when we perform a threshold analysis, 546 00:24:21,620 --> 00:24:25,480 we found that those resections above 20% 547 00:24:25,480 --> 00:24:27,460 and less than 60% were the ones 548 00:24:27,460 --> 00:24:31,420 that were related with a significant increase in 549 00:24:31,420 --> 00:24:32,140 overall survival. 550 00:24:33,480 --> 00:24:36,940 So to summarize our findings, we did this 551 00:24:36,940 --> 00:24:40,020 illustration that just shows that, you know, in 552 00:24:40,020 --> 00:24:42,340 the green part, in the green portion, are 553 00:24:42,340 --> 00:24:45,360 the percentages from above 20% and less 554 00:24:45,360 --> 00:24:47,260 than 60% that were related with an 555 00:24:47,260 --> 00:24:48,320 improved overall survival. 556 00:24:48,900 --> 00:24:51,340 And we didn't find significant benefit in those 557 00:24:51,340 --> 00:24:53,800 resections above 60%. 558 00:24:53,800 --> 00:24:55,980 That is the red portion of the figure 559 00:24:55,980 --> 00:24:56,340 here. 560 00:24:57,660 --> 00:25:01,060 So now we know that increasing SMR is 561 00:25:01,060 --> 00:25:06,020 beneficial for an improved overall survival in our 562 00:25:06,020 --> 00:25:09,080 patients with IDH-type, wild-type GBM. 563 00:25:09,620 --> 00:25:12,340 But we know that there is also a 564 00:25:12,340 --> 00:25:16,820 high variability in the radiological presentation of our 565 00:25:16,820 --> 00:25:19,540 group in general in GBM, but also in 566 00:25:19,540 --> 00:25:20,300 IDH wild-type. 567 00:25:20,760 --> 00:25:23,000 So we partnered with the Mathematical Neuro-Oncology 568 00:25:23,000 --> 00:25:25,920 Laboratory at Mayo Clinic Arizona with Dr. Christine 569 00:25:25,920 --> 00:25:35,480 Swanson to try to further personalize the, to 570 00:25:35,480 --> 00:25:39,980 try to be more specific with using specific 571 00:25:39,980 --> 00:25:43,020 patient characteristics from the radiological data. 572 00:25:43,540 --> 00:25:46,120 And we can see that following our hypothesis 573 00:25:46,120 --> 00:25:53,000 at the center of the lesion, the one 574 00:25:53,000 --> 00:25:54,780 that is in close proximity with the contrast 575 00:25:54,780 --> 00:25:59,080 enhancement part, has a greater tumor burden cell 576 00:25:59,080 --> 00:26:00,620 concentration over there. 577 00:26:01,000 --> 00:26:02,540 And once you are going to the periphery, 578 00:26:02,680 --> 00:26:04,980 you see that the low density, that the 579 00:26:04,980 --> 00:26:08,360 density of these tumor cells is lower. 580 00:26:09,400 --> 00:26:12,160 So this is the formula that was used 581 00:26:12,160 --> 00:26:13,600 in our patient population. 582 00:26:14,540 --> 00:26:16,160 In summary, for the interest of time, you 583 00:26:16,160 --> 00:26:18,440 can see that in the T1 with contrast, 584 00:26:19,000 --> 00:26:22,180 the volume was approximated to an aspheric shape. 585 00:26:22,680 --> 00:26:26,140 And we saw that this part, this portion 586 00:26:26,140 --> 00:26:30,400 has a greater cell density compared to the 587 00:26:30,400 --> 00:26:33,200 cell density in the T2 pair. 588 00:26:33,960 --> 00:26:38,060 So with these results, we classified our patient 589 00:26:38,060 --> 00:26:41,240 population in three groups that were nodular, moderately 590 00:26:41,240 --> 00:26:47,140 diffused, and highly diffused according to their tumor 591 00:26:47,140 --> 00:26:49,160 cell density and distribution profile. 592 00:26:51,890 --> 00:26:55,250 So this is a representation from some of 593 00:26:55,250 --> 00:26:57,210 the patients that were selected and classified and 594 00:26:57,210 --> 00:26:58,850 included in these three groups. 595 00:26:59,050 --> 00:27:00,590 You can see here in the nodular, they 596 00:27:00,590 --> 00:27:04,710 have more contrast enhancement than flare. 597 00:27:04,830 --> 00:27:06,430 And see in the moderately diffused, you see 598 00:27:06,430 --> 00:27:09,210 that there is some more flare in the 599 00:27:09,210 --> 00:27:14,490 patients surrounding the post-gastrointestinal T1. 600 00:27:14,830 --> 00:27:16,470 And in the highly diffused, you see that 601 00:27:16,470 --> 00:27:19,070 the flare is greater than in the other 602 00:27:19,070 --> 00:27:19,530 groups. 603 00:27:21,960 --> 00:27:24,100 So for this, in the univariate analysis, we 604 00:27:24,100 --> 00:27:28,840 saw that it was statistically significant only for 605 00:27:28,840 --> 00:27:31,980 moderate and diffused and highly diffused. 606 00:27:32,340 --> 00:27:34,740 But it was not significant for nodular. 607 00:27:35,020 --> 00:27:36,060 This is in univariate. 608 00:27:36,560 --> 00:27:38,900 And the same results were obtained for the 609 00:27:38,900 --> 00:27:39,820 multivariate analysis. 610 00:27:40,140 --> 00:27:43,240 It was statistically significant for moderate and highly 611 00:27:43,240 --> 00:27:44,460 diffused, not for nodular. 612 00:27:44,580 --> 00:27:48,120 But when we performed a tracer analysis, we 613 00:27:48,120 --> 00:27:52,200 saw that for the nodular, there is actually 614 00:27:52,200 --> 00:27:56,620 a benefit only in resections from 10% 615 00:27:56,620 --> 00:27:57,340 to 10%. 616 00:27:57,340 --> 00:28:00,880 And this is kind of logical because, you 617 00:28:00,880 --> 00:28:02,380 know, in the nodular, there is not much 618 00:28:02,380 --> 00:28:06,420 flare, as we showed you in the MRI 619 00:28:06,420 --> 00:28:06,980 before. 620 00:28:07,540 --> 00:28:10,940 So there is not much benefit in extended 621 00:28:10,940 --> 00:28:14,440 resection beyond the 20% of the contrast 622 00:28:14,440 --> 00:28:16,420 enhancement in the nodular group. 623 00:28:17,100 --> 00:28:20,500 In the moderately diffused, we found benefits from 624 00:28:20,500 --> 00:28:23,180 all the way up to 50%, you can 625 00:28:23,180 --> 00:28:23,600 see here. 626 00:28:24,460 --> 00:28:26,500 In the highly diffused, we only saw benefits 627 00:28:26,500 --> 00:28:30,020 beyond 30% all the way up to 628 00:28:30,020 --> 00:28:31,760 90% and 90-plus percent. 629 00:28:33,460 --> 00:28:36,340 So this is very important because now we 630 00:28:36,340 --> 00:28:39,140 can, based on this study, at least in 631 00:28:39,140 --> 00:28:41,740 these results, we see that there is a 632 00:28:41,740 --> 00:28:46,080 very important benefit in the supramarginal resection of 633 00:28:46,080 --> 00:28:46,980 these patients. 634 00:28:47,120 --> 00:28:52,620 And of course, based on their radiological characteristics 635 00:28:52,620 --> 00:28:57,320 before the surgery, the surgeons can decide how 636 00:28:57,320 --> 00:29:01,260 much the patients can need a resection, an 637 00:29:01,260 --> 00:29:02,700 extended resection based on this. 638 00:29:02,800 --> 00:29:05,540 And for example, in these highly diffused tumors, 639 00:29:05,680 --> 00:29:10,120 we found that this is the maximum SMR 640 00:29:10,120 --> 00:29:12,560 correlated with beneficial viral survival. 641 00:29:13,040 --> 00:29:14,940 You can see that patients that had a 642 00:29:14,940 --> 00:29:19,960 resection above 90% had a better overall 643 00:29:19,960 --> 00:29:21,880 survival than the ones that had less than 644 00:29:21,880 --> 00:29:22,720 90%. 645 00:29:22,720 --> 00:29:26,600 And this patient population had a greater survival 646 00:29:26,600 --> 00:29:31,600 of, let's see, if I remember correctly, almost 647 00:29:31,600 --> 00:29:34,120 nine months greater than the patient that had 648 00:29:34,120 --> 00:29:36,750 a resection with less than 90%. 649 00:29:37,630 --> 00:29:41,930 For the moderately diffused, the highest SMR percentage 650 00:29:41,930 --> 00:29:42,610 was 50. 651 00:29:43,210 --> 00:29:47,610 And this patient presented with a benefit of 652 00:29:47,610 --> 00:29:49,810 an additional seven months. 653 00:29:51,390 --> 00:29:54,550 And in the nodular patients, the highest maximum 654 00:29:54,550 --> 00:29:57,970 significant SMR correlated with beneficial viral survival was 655 00:29:57,970 --> 00:29:58,750 20%.