 Thank you for the rest of the ecology faculty. That was a fabulous start to this day. Very interesting discussion. I learned a tremendous amount and I will think twice again before I enter an eye, especially a total retinolase hashing type case. Thank you. It is my true honor to introduce our next Knights Templar Eye Foundation keynote lecture. Brenda Galli. As you can tell, she wears many, many hats. She's the director of retinoblastoma programs, not only one department but two, and Sick Kids Hospital in Toronto and Alberta Children's Hospital in Calgary. She's associate scientist and lead health informatics research at Tacna Institute and Cranbull Research Institute, University Health Network in Toronto. She's a professor of departments of ophthalmology and medical biophysics and medical genetics at the University of Toronto in Canada. She leads team at Sick Kids that has developed a state-of-the-art care for retinoblastoma across really all of the Canada. She has more than 40 years of experience in this research arena. She really is implementing a novel retinoblastoma point-of-care database that helped to improve understanding of the treatment course and to support lifelong multidisciplinary care. Without further ado, I would please ask you to help me welcome Brenda Galli and her title of her talk is New Green Landscape for Retinoblastoma. Thank you, Brenda. Well, thank you very much. I've really enjoyed this meeting. I've not been to this meeting before, but it's just had a wonderful atmosphere of discussion and collegiality and fantastic new ideas. I've learned a great deal here yesterday and this morning. Thanks to the panel who did a marvelous introduction to what I'm going to talk about, I'm going to talk about, first of all, I will say I do not have a disclosure slide, but I'm only paid to care for children at the hospital for sick children and Calgary as a salary in both places. So none of the other, many of these icons on this slide actually donate and raise money for the research that I'm going to talk about. None of it passes through my hands. Green, green. What do I mean by green? What on earth am I going to talk about here? So this is my last slide. Don't read the details yet, but I'm going to end up with seven points on why the care for retinoblastoma at the present time is very, very exciting because a lot of things are changing that will make the care greener for the patient. The patient will suffer less, endure less, and have better outcomes. And our real goal, which I haven't mentioned much in my talk, is that no child should die of retinoblastoma anywhere in the world. So the first piece there is life, vision and eye. That's the first thing to recognize that life is more important than vision and more important than an eye. And that concept has come out strongly and it was reiterated here. However, I would appreciate discussion over which comes first, vision or eye. What's the priority there? Is a blind, dangerous eye worth saving? So that's a, I won't answer that. So the standard of care for retinoblastoma 2019, and of course there could be variations on this that I won't put here, but this is very much the sort of textbook and what you've already been brilliantly led through this morning. I'll start though with classification. We all still use ABCDE as if they're all one standard, but they're not one standard, and that was recognized and the paper, the American Journal of the AJCC Cancer Staging Manual, which has cancer staging delineated for all different cancers. The eye is included and retinoblastoma has a chapter, Ashwin Malapatna led that chapter with many, many people internationally working on the content of that. But the data in that chapter is in part, partly consensus across the world, but partly based on a survey we did, which had 10,000, 1,067 patients scored for the possibility that an eye with certain features could be saved. We're not talking mortality because the mortality in the whole study was very low. This included 19 centers around the world who entered data into a database, which was sort of similar to our, the depict health that was nicely introduced, which I'll talk more about. And that showed that the, there was a problem. The data that was submitted was features of the eyes. And then the algorithms designate classified the eyes by five different classification, starting with the Reese Ellsworth, which was developed in the 1960s, basically to predict outcome of radiation to the eye, to possibly to save the eye and working all the way through to the ABCDE. But there's two versions of the ABCDE that are critically different. And the Murphy version, published in 2005, did not take into any consideration the size of the tumor in the eye. In other words, he felt from his observations that size didn't matter to the ability to save an eye, even very large tumors could respond. The other version published in 2006, the Shields version, put 50 percent volume, more than 50 percent volume of tumor into D. And that meant that eyes would be moving from D to E, if they had a larger tumor. And that changes everything. But this, this, this survey showed that, um, that mushes all these and these together, meaning you can no longer tell which eyes should be a nucleated, Murphy said, E stands for a nucleation. So the new classification, the eighth edition is CT, following the standard for all cancers. And T1 are very small. T2 are the ones really can, the eye can be saved. And T3 should all be high level consideration to a nucleation. So I'm going to just mention first some exciting things in my number two there, you see the green two. That's the second exciting opportunity as OCT for retinal blastoma. And I'm showing you here a family. The grandmother had bilateral retinal blastoma, bilateral nucleation in the fifties, saved her life. She lived a wonderful life then died of her second cancer, sarcoma, but she had two children, one who carried her mutation. And I treated that child and has 2020 in two eyes with small tumors in both eyes. And then that mother, the first H1, had two children. The first child is H0, no retinal, no mutation. And the second child diagnosed at 33 weeks gestation to carry the mother's mutation. So the baby was elected to be delivered at 36 weeks gestation instead of waiting, because we know at 36 weeks, they already have a 30% chance of a vision threatening tumor. I just didn't mention that the H here is derived from the new classification. So retinal blastoma is the only genetic cancer. Isn't that interesting? It's the first genetic cancer that acknowledges in this staging system that heritability has something to do with prognosis. And so it's now the TNMH, but only for retinal blastoma. The other cancers have to wait for the ninth addition before they can add an H. But it's interesting the way I've used H here. It's so easy to talk to a family about who carries the mutation. Maybe other eye cancers could think about using a similar system instead of having to go into the detail with each patient of what the mutation is, et cetera. That's a bit of an aside. So in this particular patient, the little girl with H1 here, right? Oops, not working, right there. When she was, we monitor these children in the clinic awake with both RETCAM and OCT, hand-held OCT in the clinic. And then we all went home and Leslie McKean phoned us. We all watched the OCT. Leslie McKean phoned us and said, you got to come back. We missed a tumor. And it's because we were watching it happen fast and you've got to go through every slice of the OCT. And this is a tumor that was found later. You can see where it's the second image here is when it's already indenting the retinal surface a little bit, it's still quite invisible. But when we went back to our previous 45 days before, it's actually there, and so we missed it because it's only one OCT slice. But it was all right because this wasn't threatening vision. And then I show how it's, it's hard to find. So we put one laser burn in, in order to know where the OCT was in order to know where it is because you don't know where to aim the laser. Yes, by the blood vessel pattern. And then you add more laser until it's all white. So we use the OCT as well to judge that we've actually not got a geographic miss. And then in follow up, we can see there's a nice scar and no recurrence. But we also use OCT to use for surveillance for recurrences. So OCT is a key part of managing the focal therapy treatment in retinal blastoma at the kids and Calgary. So for unilateral, the other eye is normal. First line and second line therapy are very reasonable. And all these things have had a good introduction to that already. Third line becomes questionable for a unilateral. The other eye is normal. Should you put the child through all of this, taking them away from playing and enjoying life in order to try and save a lot and I that might have vision or not. And so we kind of would put a barrier on that if less vision potential is very good. For bilateral last eyes, we do go to the third line therapies, including at the last ditch, external beam radiotherapy still may have a role for an eye that has vision in the last eye. But here we're after keep in mind life versus eye. We have some brand new data, which is now just published, showing, giving some idea of the clinical features, looking at the child to say that there will be low risk pathology in this eye and it would be safe to go through trial eye salvage. And there's only 38 patients in this study, but it does statistically show that if the optic nerve is visible, the macular is visible and there's less than a quarter, of retinal detachment, it's there. None of those eyes had high risk pathology and all the eyes in the study were nucleated and this is over in the past when we didn't try to save them like this. So that puts a nice guide onto which I to try to save. Another study that was presented at Arvo and is submitted now from data from China has a much larger N, 544 patients in this study, covering four years and these are all eyes that were nucleated. So it doesn't count the ones that had attempted salvage and succeeded. So these are eyes that did not succeed. So that's a problem of this paper. We don't know about the other ones because we don't have pathology on them. And what it shows very clearly is that pre-inucleation chemotherapy, which is broadly given, thinking to try and save the eye has no survival benefit. Mortality is the main outcome of this study and delay actually worsened survival. So if you keep trying to save a group DI for more than 3.5 months or more than two months for a group EI, you're actually entering into survival risk. So that's important to think about. Nobody knew it so clearly as this right now. This data is very important. But once you enucleate the eye and you see high-risk pathology, PT3 or PT4, then systemic chemotherapy actually has a major impact to improve survival. So it's well worth doing. And we could talk more about that, but I don't think I'll take time. It's very interesting observation. So you'll see vitrectomy and we've heard about the dangers of sticking a needle in the eye even to do anything. And now I'm talking about vitrectomy. Well, last year, Dr. Jan-Yang Cao and colleagues let me help them. So I'm an author on this paper to report the first 21 cases of Pars plaintive atrectomy and endoresection of refractory retinoblastoma. These cases were all done in the first half of 2013, so there's very long follow-up. And that showed that it was safe and useful with good vision outcome in a significant portion. But now at the ISO meeting recently, so brilliantly led by Jesse and colleagues, Dr. Zhao presented on 159 patients, 174 eyes. And you can see that 2% died from the eye that had the PPV with optic nerve invasion and blood metastasis, but there was zero evidence that this was related to the tractomy procedure. There was no anterior disease, which is consistent with the international data on the intravitral melphalan injections. So this child that I show here, the top left picture, this is a child in Kenya. And the first picture was when I saw her maybe five years ago in Kenya with Dr. Kahaki Kimani, who's a brilliant retinoblastoma ocular oncologist. And then I got pictures sent to me by Kahaki showing vitreous seeding and growing in that mass. They gave many more cycles of systemic chemotherapy. They could not do intravitral melphalan because they couldn't have the drug in Kenya. And I knew about the PPV from China. So we organized that this little girl, and I can use her name, Sharon, went with her parents to China, had a PPV, and this is immediately after the PPV, you can see that the tumor has been, the tumor where the tumor was, is surrounded by endolaser to stabilize the retina, and the tumor base and all the vitreous seeds are gone. And then she went back to China to have the silicone oil removed and where followed her ever since. She has a nice, flat, white scar. Her fovea is on the other side of the optic nerve and has 20-20 vision, so this little girl's only other option in Kenya was to lose her last eye. So it's a very exciting, exciting approach that can come in and clean up the refractory issue and cut short all the other things we keep doing, non-green things to invade the child and try to save eyes and vision. So here's depict health. This is a child I'm gonna, that follows through on what I was on the vitrectomy, but first I'll introduce you to depict health. This is a database that is on the cloud, so it can be seen anywhere. The demo is running. It's actually not on the cloud, but soon will be moved to the cloud. And you can go and log in. I'll give you the logins. I'll give you a card with it all written on it. And this is home base. This is the whole scenario for this child. So you can see that the TNM scoring is written up here. So this is both eyes, well, this is unilateral. You see this is a TTT zero. Nothing is ever needed for this eye. And this is the TTTB. But this algorithm of the full classification comes from not from the doctors remembering anything. All they do is enter the data, the features of the eye and the database does the classification, including the H staging. But this child is H zero after testing. And the green line shows when the genetic test was done. And it's H zero because no mutation was found in this unilateral patient's blood. But we add an asterisk now, and this isn't in the textbook, because there's a residual risk that that child's actually mosaic at a level that we can't detect. If we had tumor, we could maybe find the test with more precision for the second event or for both events that we would find in the tumor and find more mosaicism. But we don't have tumor at this point. And so we add an asterisk for that caveat. So you can see the child has had initially intra-arterial chemotherapy. That was the only successful intra-arterial chemotherapy. On the second intra-arterial chemotherapy with quite a nice response in the eye, the child actually stroked on the table and ended up in the ICU. This was well managed because she was already still there. They still had a catheter in there. Everything was managed, but she has a tiny little ischemic area of brain that remains. And so what does that mean for this child in her life? She's functionally perfectly normal right now. So we gave her two cycles of systemic chemotherapy. And then all the vitreous seeds had disappeared. So we put in a plaque. I'll go on to the next slide. This is what she looked like at the beginning. You can see unilateral, the right eye is totally normal. So I'm not showing its timeline anymore. And the tumor is leaving her with an intact fovea, you would guess. And if we go to this picture, you can see in more detail that she has really very extensive vitreous seeding all over. And here's an OCT across with a normal fovea and optic nerve and all this seeding sitting on top of her fovea. But it moves around. So that was all at, sorry, that was at diagnosis. So we did all those treatments, including putting a plaque under this. And then we came into this follow-up visit and noted that we couldn't see very well and there was a retinal detachment. So laser near the plaque tumor, this is the source of all the seeding. This is the main tumor right here had caused hemorrhage and we projected that there would be a hole, a tear on the edge of the calcify part of the tumor. So that was quite magical because, not because that happened, but because I texted to our retinal surgeon colleague who has moved from Toronto to Hong Kong, Weicheng Lam, who's done several of these vitrectomies following along the Chinese approach in Toronto. And he woke up and looked at his texts and he said, wow, I'm going to Toronto tomorrow. So he was landing, this was Wednesday when we texted him. Thursday he landed in Toronto and we did a vitrectomy on Friday morning. So it was amazing circumstances. He's a very brilliant, careful surgeon as is Dr. Lee who works with Dr. Xiao in China. Both of them are very calm, quiet, people who care a lot about children. And it's quite beautiful to watch the work they do in just the right children child. So it's a real team of a big retinal expert, Dr. Chow and his retinal surgeon who doesn't choose what to do. He follows the guidance but does it with beautiful precision. So now you can see post vitrectomy what we're left with and resection. We're left with a broad band and this is the scar from all the endolaser. And here is normal retina coming up. The retina is now attached and there's silicone oil in the side at this moment. And here we go to scar. So we're going from attached retina into scar right there. And up here we're going from scar here into coroid. And there's the coroid and the retinal blastoma has been carefully peeled off Brooks membrane in the coroid and that's the resection technique. So depict health, here you are. I'll give you cards. It's really easy to get into. Just put in demo user. One thing state people sometimes make is they think they should put an S there because this must be secure. It's not secure. I want you all to go and look at it. You can enter patients. You'll see the patients I've talked about here. They're timelines. They are all masked. The dates of events are real because we can't make up a retinal blastoma case but their date of birth and their names are different and the children have picked their own name. So they're interesting names. Actually the first child in that I showed you whose grandmother died of a chocoma. Her initials are VV so she's Vincent Van Gogh. So here's what depict health does for the whole team. The data is entered by the whole clinical team. The family views and can assign anybody they choose to also view but they can't enter data. Subsequently newer versions will get into stress response courts from the parents et cetera and the family and the patient and all sorts of other things where they will enter the data and we will only view but that's not developed at this moment although this is built on a core of E cancer care which is within the whole UHN University Health Network and there the stress response core is fantastic. Patients in the waiting room on an iPad give indication of how well they're really doing and that changes their management significantly. And it makes the whole circle of care including the family a real team. So that's my number six. You'll see the number six there for making things better. Depict health is going to and the secure access portion is already on the Microsoft Azure cloud. The newest version of the databases going to be going up with it a month onto the cloud and then the demo will rerun another demo because it still will have things you can make suggestions on how we can make it better before it actually achieves all its governance processes and there's an extensive governance processes designed including the organization. For example, all these committees that will oversee this are consistent of people who are the leads and the heads and people at all the sites in the world they'll all take turns participating and one day we'll even get to the point where there's inspections, just like along the model of the pathology, the CAP, College of American Pathology has beautiful system of each lab inspecting other equivalent labs and I've done that myself. It's quite fun, it's very exciting and I see that to work here too. And then everybody is partaking in it and working together to make this all happen. But out of that, the data that goes in is identified but with minimal identifiers, but you can't care for a Muslim patient without knowing which patient you're talking about and we want to be able to invite our colleagues anywhere in the world to look at that patient and we just give them access to the database. We don't need to send anything through the email. We don't need to talk about it. We just send them the link and then they can look at everything. And if the patient travels to another center they would also add data to that patient's record but it's one patient record everywhere. Then out of that will come coded data that's the real world data because this isn't a study, isn't a project prospect to study. All the data that happens lifelong will then go in and then we'll have brilliant machine learning or artificial intelligence that will feedback to give us better evidence for what we should be doing with the next novel therapy. Here's a child. You can see the child had bilateral nasty retinoblastoma and you can see the yellow triangle is a nucleation and this eye was taken out within four months, reflect back to 3.5 months for the DI, would say we need to get it out pretty soon and that was done. That left us with the other eye which has had, as you can see from all the symbols, a lot more treatment and this is what the eye looked like after systemic chemotherapy, intrarateral chemotherapy, lots of laser and then the fovea detached and fovea detached because the main source of tumor sitting here nasal to the nerve had started to grow again and all the yellow in this drawing and these are the standard same drawings that have been done for retinoblastomas since 1950s when the indirect ophthalmoscope was used and it's the same template, same piece of paper but this is a vector coordinated diagram in the thing. Am I going too long? Okay, I'll go faster, okay. So this child had all these tumors, all 31 tumors all over here and then I talked to Lynn Murphy and he introduced me to the fact that the episcleral chemo plaque was ready for being put in a patient but hadn't been put in any patient so I worked very hard to actually get permission to do a special access patient one and this is what it looked like before we put in the plaque and this is what it looked like after. This child has gone on with many more things and we still needed to do more but is doing well today. So there are three trials in the cooker and one in LA, one with Dan in Houston and we're putting together one in Toronto as another phase one. They're all different and different patients. I'll skip over this except that maybe this chemo plaque will one day prevent the scar that we end up in patients like Vincent Van Gogh. So here's why green, these are all the things I've talked about because over time I won't go right to the bottom, strong collaboration, make retinoblastoma not so rare and good retrospective studies with long followup and large end will change a lot of things and new prospective fully documented studies will achieve evidence for best care. Thank you very much. Sorry, these are all the people that really do the work and have done the work and they're color coded for what center they're in and the major donors I have to point especially to Paul Fingers organization to help this all happen. Thank you very much, Dr. Galli. That was a brilliant lecture. This keynote lecture is open for questions from the audience. Sir in the back, if you can give your name please. Dr. Lu from China. Question to the panelists. The last year I have a very bad misdiagnosed cases. The patient was a four year boy came that presumed to be toxoclerosis because not only because of the clinical features that traction vitreous case but also a very strong indication from the lab test that telling us that yes, the lab test is positive for toxoclerosis. I want you to comment on the false positive lab test that might lead us to the misdiagnosis of retinoblastoma. I learned from the literature that the number one indications that from the false positive test is retinoblastoma. A question to the panelists. Yes, thank you. I'll share with you the 15 year old case in our center which mimics some of the challenges. And I discussed this case with enormous humility because sometimes people like a panel like this will say you should have thought about this and I completely disagree. These are just very sometimes very unfortunate cases but this is a 14 year old African-American male who was noted to have a granuloma or thought to have a granuloma and had an extensive workup by very smart people and ended up having a quantiferon gold positive test and the diagnosis was tuberculosis. The eye continued to be monitored, eventually went to buphthalmia, had a scleral melt and subsequently was enucleated because the presumptive diagnosis was infectious. The eye sat actually until the ocular pathologist looked at it for a couple of months because she was focused on more neoplastic concerns until the eye ultimately was looked at and of course it was retinoblastoma and by the time we realized that the child already had CNS metastasis. And I don't think anyone would have thought about retinoblastoma in a 14 now 15 year old child. So there are these very challenging unfortunate cases where we look for clues and sometimes the tests that we have reinforces the wrong diagnosis and I think we're always going to have that. There is going to be within the next year a very nice paper that has been submitted will be published from the Children's Oncology Group. So for those of you that do a lot of pediatric work, you're familiar with COG, it's the largest NIH NCI sponsored consortium of pediatric oncologists designed to support prospective multi-center well-designed trials in pediatric oncology. Ira Dunkel led this particular trial looking at extraocular disease and we always think of extraocular disease as something that's going to lead to death. And there are two encouraging aspects about this data which will come out. First of all, stage two, three and four A disease which is extraocular local or distant metastasis not involving CNS, the prognosis is not that bad with aggressive chemotherapy. So multimodal chemotherapy often involving a stem cell transplant, we are starting to approach 70, 80% five year survival for even stage four A disease. So distant metastatic disease not involving the CNS. Where there is horrific prognosis with very poor five year survivor, we're looking at less than 10 to 15% five year overall survival is with CNS metastasis. So I think there is some potential that in a case like yours, as long as we can get to it before it's in the CNS, we can recognize these patients, we can still potentially cure this patient with aggressive chemotherapy. And that paper is going to disseminate within the pediatric oncology community within the next year worldwide. Question for Dr. Galli in the back. Ma'am. Hi, I'm Mike Shapiro from Chicago. So I think that the most problematic rabbit hole for me is the parents who really seem to be dead set against their nucleation whether it's unilateral or bilateral. And I think one of the most important points you've made is the issue of losing survival while going down this rabbit hole. So how do you talk to the parents and prepare them for the possibility of how do you solve this problem for me? We didn't ever used to have such problem to get eyes removed. And maybe I'll pass to Brian until the basketball player went public with unsubstantiated no research to show its value and the whole nation and the world thought we can save any eye with retinal blastoma. So that led the parents to put extraordinary focus on the eye even without vision. And I think that's caused a lot of trouble worldwide. But I think depict health might help that because the parents are invited to watch. They can see all the treatments that the child's had and all that they can look at other children, other example children and see when they conduct, you work for two years to save an eye and then take it out anyway, having risked the child's life through that interval. All of that information in parents' hands, no parent wants their child to die. I think that might be a way to change it but it is one of the major problems in care of retinal blastoma today. Thank you. So I'll just add to that. I think it's really important to exercise the quality of the vision in those cases and say, we can chemo a nucleate your eye with all these technologies but we're not really saving a functional portion of the patient's existence. And you have to drill that home to them. Even though we can do it, there's reasons not to do it. And the treatments are involved and painstaking. And if you can just kind of convince them that why are we doing this? And they can think a little bit about how to answer that. A nucleation is easily sold. I think also in the era of social media, while we had some help for saving eyes from basketball players, unfortunately, and we've lost some children in this country from aggressive attempts to save eyes that should have otherwise been removed because the eye was blind and dangerous and those are now really readily available in the newspaper on Facebook. And so that's something I discuss with my parents as well that I wanna get your child to prom into college and he or she can do that regardless of whether or not they have an eye but they can't do it if they lose their life. There was a question in the back. I'm Linda Sanichara from Mexico City. Part of my practice is based on pediatric retina tumors. And one of the new perspectives here, I would like to ask if you think at some point the accused humor biopsy will be helpful for those complicated cases as well that we always have questions whether it is or not a tumor. So right now, and I have to stress this, it is all research. So there's no current clinical test or clinical indications for the aqueous humor. I do, however, hope that it will be helpful. Right now it's shown a lot of value in terms of prognosis. So which eyes are more or less likely to respond to therapy? We and a center in England have also shown the ability to detect RB1 mutations in the aqueous which in a non germline case could help with diagnosis. That being said, again, right now, if it takes eight or nine weeks to get the RB1 mutation, it's not a big deal because we're doing research to be able to do that rapidly in a clinically useful manner. It's still not something we've achieved. Dr. Hardnett. In the patients who ended up having parasplain of atrectomy, do you give like intra systemic chemotherapy right before or how, when are you, do you ever get worried that it's too active to resect it or? These eyes have all had systemic chemotherapy and they're all for failed. So there are recurrences and different things. We don't give more systemic chemotherapy right before necessarily and there are more than 700 of these done in China now and there's no evidence of that but we're only reporting the ones that have long follow up but it doesn't seem to be a problem and but the irrigation fluid has mouthful and in it at a low dose and we take everything that comes out of the eye, we examine under the microscope. For example, that one I showed the recent one we just did, we got a report on the cytology from the irrigation fluid that it had retinolastoma tumor in it but when we look at that slide, all the fluids on one cytology slide, it's because we resected the tumor. So it's an interesting view of the tumor that was irradiated a few months before with a plaque and they don't look like active retinolastoma cells to us. So I think it's certainly you're taking out cells. Along that line, Francis Mounier, just to Dan's comment on intra vitriol mouthful and we sent one patient to Francis for different things and he did the anterior chamber tap before intra vitriol mouthful and he, not only send pathology, he grew it in tissue culture and it had live retinolastoma in it. It grew in tissue culture and that led him to recognize that when you do that anterior chamber tap there actually could be pulling cells from the back of the eye into the anterior chamber. That doesn't seem to be any problem for disease extent and anterior disease is not a big problem, although we all thought it would be, but it shows and Francis's response is now he does bicameral drug into the front and the back because maybe he's pulled some forward. So it's a lot of things. Just a quick comment. When we do anterior chaps all as a security check, everything is sent to our cytopathologists that day and we have never detected any malignant cells and any AC tap that we've done. So, and that continues to be an internal control for us. That's our standard. I think it's safe to say that there's still a lot to be learned about the safety of employing vitrectomy. I saw everyone, all the vitriol and those surgeons, their eyes has kind of popped open when you described it. So I think there's much that we're eager to learn about how to manage this. So again, thank you to Dr. Galli for a wonderful lecture. Thank you, Professor Galli. It's been an outstanding work and thank you for leading the way to improve care across the globe. Thank you. This is just a little bit of Utah to take back with you. Wow. We're pleased we can definitely ship it for you. We're happy that it is a beautiful piece of Utah. Oh, wow. We'll look at it. And he's been very nice. I like that. Thank you very much. Thank you.