J Mocco, MD, MS, Senior Vice Chair of Neurosurgery at Mount Sinai Health System and Director of the Cerebrovascular Center, discusses the importance of exploring curiosity in medicine and details his own experience with conducting research projects and clinical trials to find solutions to problems often encountered within the field of cerebrovascular neurosurgery.
Chapters (Click to go to chapter start) How Dr. Mocco was first exposed to neurological research in medical school and the major lesson he learned about being curious A question Dr. Mocco posed early in his career and how it led to a clinical trial on framing with larger-diameter coils to treat cerebral aneurysms, as well as a statement made on coiling small aneurysms and the clinical trial that came out of it How standards for stroke thrombectomy were challenged Other areas within cerebrovascular neurosurgery that still need to be explored further Conclusion and Q&A/discussion Referring a patient is easy. Just click the “Refer a Patient Online” button. Maybe we'll give everyone another one minute to get on. But we're over 50 people a couple of minutes here. Yeah, We're up over 50 attendees already. So they're moving quickly. Yeah, I thought that was a really interesting presentation and uh we should definitely get them back to to do more. I will really interested to hear their advice on text messaging and recordings during surgery. Right, me too. And you know, we need to we should review again the possibility of our conferences, the comments at grand rounds, all those things, There are very specific rules that relate to that. Um Hey peter, what do we do? Like, are there, are there questions, is there discussion at the end? How does that work? In this point? People will be able to raise their hands to ask questions so we can promote them to speak chris and I will watch the watch the list and then there's a QA in chat box but we'll monitor that. Mhm. It's 8:05. We have 77 people on let's get started. Um So this is an exciting moment. Not every day that we get to hear jay marco speak to us, everyone knows him. But just to point out a couple of a couple of highlights, jay is an internationally renowned individual. I don't think that I have met a single neurosurgeon anywhere in the world who doesn't know about J Mako who doesn't actually know J. Mako And who doesn't admire him 1 1 way or another. Um You know, you can see his titles here, professors, senior system, vice chair director of the vascular center and so on his education and so on. They don't really tell the story of his energy and his enthusiasm. I've never met someone who is able to balance a vision with energy drive and productivity like jay. Um He's creative, he's incredibly fun to work with for me and I consider him a close colleague, a mentor, a friend and someone who I admire. one of the things that I always love about presenting uh something about J is that no matter what you say. So for example, here this slide that was recently done. Mhm. He says that he's got more than 500 peer reviewed publications. It's always out of date. And so um this might have been made a couple of months ago, but if you were to look today, you'd see that it's more than 565. That's because every single day there's something new that's coming out that jay has done. Um So it's a great pleasure to introduce him, but I also need to share my screen here because 11 of the funny things that you get when you pull up the web and you look at J is that he's he's all over, all over the world and all over the internet. Um of course this picture on the top right here is my absolute favorite from university of florida. Um But you just get a sense of someone who is not only deeply engaged in what he does at any particular moment, but who has interests in many, many different areas. Uh, so with that we'll turn it over to j to hear his talk today. Thank you. Thank you very much. I gotta figure out. I saw one of those pictures, it had Nathan manning photo with my name. I gotta figure out to make that happen more. He's a really good looking guy and if that would be a plus. Um all right, let me share my screen. Mm hmm. Okay, that's sharing, correct? Yeah, I can see that perfect figure out where to put everyone. So thank you. It's it's an honor to get to talk to all of you. Um, you know, to be honest, in typical fashion, you know, I got an email from a list asking for the title on friday and I thought, oh my gosh, how am I going to get this done in that time? And so I've been putting this together sort of in the hours from 12 to 2 am, But, but I love when I get to do this because it gives you a chance to sort of reassess its like a moment. It's almost like a moment of mindfulness where you kind of focus on where am I, what have I been doing and and where things and and what's meaningful to you right now, what have you been thinking about? And, and so, so that's what I'm going to try to share with you guys. I'll go over some facts and things. But really I'm hoping to give you some insight into kind of what makes on some level me tick. I think a lot of our CV team tick and hopefully give you some lessons that might be worthwhile to take away. It's not clicking. Oh there briefly these are my disclosures, the P. I. And a bunch of trials of which will talk about pretty much all of them. I think I don't think I referenced bill and I have invested in and consulted with a bunch of companies. I don't think I talk about any of them in this talk and I was recently made a pea eye contact the eye for stroke net. You one grant currently unfunded but we'll be resubmitting in in the fall. Um and I will talk about that and and the connections to that. So to talk about CV problems and using research to figure those things out. I thought I'd start at the beginning um which for me is, sorry, I don't have major problems here. Maybe if I move my keyboard here, which for me kind of a third year med school. So by way of background, I went to University of Miami. Um we didn't have a lot of means as my family. So we I was a college, I got a college work study and I got a job with the chairman of neurology totally random. My guy didn't pick it, it just got assigned. I might have been checking people into the gym or working in the admissions office. It's just what I got assigned and and it was neat and the guy was neat, it was fun to drive, go over to the medical school, but I was doing research with him. He had me accounting nuclei endorsers jokingly and and I finished that experience thinking I hated research deeply and I didn't want to ever do anything in the area of research. Um I was like, I just want to take care of patients to be very clinical. I got the third year of medical school and as, and I hope many of you had the same experience, but as you're walking around and as you're taking care of patients, there's so many, I started asking questions well, what about this? Why don't we do it this way? Could we do this? I was blown away that why is this not there? There's so many questions that we don't have the answers to. And most of the time the answer was, well we don't really know or this is where we go. And it blew my mind and it was really exciting to me that there were so many things that we really don't know about medicine. I think the average patient really doesn't get how much of this is either habit or just what someone before us did or uh sort of anecdotal practice And that was very inspiring for me. Uh and then that actually led me to seek out to do research with Sandra Connelly, you see there on your left. Uh, and and eventually department written at Hopkins and I put them up as two extremely formative mentors for me in those early years because they're the same type of people, the type of people that You, you can't spend an hour with either one of them. You can't spend 10 minutes with either one of them where they're not positing a question or wondering about how something could be done differently. Um, and it was, it was a great blueprint for where I wanted to get on what I wanted to do. Uh And in fact it led to my, this kind of an example. I want to put this in this example of my very first publication that I ever wrote. I went to a journal club. It was Stefan Maier was running an ICU journal club and they reviewed a paper on the use of an ox parent and neurosurgical patients. And in the review there were all these meaningful and appropriate critiques about the methodology and where should this lead and what should happen next. And then afterwards everyone got up and just left the meeting and I went to Sandor and I said, you know, should you want me to write up what we're all talking about and see where that goes. And he said, sure. and so my first paper ever was a correspondence in the new England Journal, the first thing I ever wrote, I was like, man, this is easy, it took me 20 years to get back into the New England Journal, um but it was the fact that he would say, yeah, medical student go, you know, let's figure this out, let's write these questions and tackle it. I think that that's important, and I think if we can bring that kind of inquisitiveness everyday to our practice of medicine, then it's hard not to want to do research, it's hard not to want to answer these questions every day in life, were presented with the opportunity to learn something new or to try something different and and that's a message I really took away from both of those mentors and still sort of reinforces my life, um there's a quote I recently came across from Einstein, creativity is seeing what others see and thinking what no one else ever thought and I love that quote and it reminded me actually, so if medical students are on and are watching, um if we're in the room, I'd look at you, but I would say, you know, when you go out and you interview and you go around the country, you get to meet all these successful neurosurgeons, you know, famous in neurosurgery terms and and ask them questions and I remember asking charlie Wilson, um what sort of what he, his advice would be or what sort of helped him be the impactful person, he was in neurosurgery, and he said essentially this quote and in fact, I wonder now if he was paraphrasing, but he basically said, you know, you go through your day, you take care of your patients, he's like, keep your eyes open and and look around, everyone's doing everything and there's stuff right there to see that needs to be evaluated and and seen more clearly, but everyone's just going by it and not addressing it. And so, you know, taking hints from people like Einstein or dr Wilson is key. I would also turn to another luminary intellectual that I think very highly of ted lasso um in front of you that haven't seen that show, I'd recommend it, although it's relatively vulgar, but it's fantastic and he had a quote, he actually interested in the show, It incorrectly attributed it to walt Whitman, but it's not actually a walt Whitman quote, but it was bi curious, not judgmental, he's talking about his experiences in life and how people would judge him and give him problems and he said, you know, they thought they had everything figured out, so they just judged everything, they just went through life saying, that's good, that's bad, but if they were curious, they would have asked questions, they would have tried to figure those things out and that's important, um it's important to not think, you have it all figured out and want to answer those questions and that's fundamental to the way I approach these things, and so to give an example of that early in my career I had the chance to moderate at the see the section moderate recession, and in that section there was little discussion was beginning about whether or not you should use these fatter, thicker diameter coils to treat aneurysms versus traditional, traditional thinner coils that were considered were felt to be safer. And so there was a little bit of discussion of this, I realized that there was some discussion going on. So I posed a question to the audience. I said how many people think that if you put in these larger diamond records you're going to get better outcomes, reduce your recapitalization, about 80% of the crowd raised their hands and at the time someone who I knew who he was, he was very famous, but I didn't personally know said it makes sense if you build a house with a stronger frame, it'll last longer. Uh interestingly, that person was Alex Bernstein, who I may be on this talk, but it's certainly someone I kinda real friend now, so it's interesting how these things go, but I'll never forget him saying it in his accent from, from uh the audience, but so that's great right, it's great, but everyone walks away from that meeting and they just say, wow, that was a fun discussion, you know, I learned something. The question is can you do more than that? Can you can you try to figure it out more? And so I started looking at the evidence and I said what do we have? And the answer is there really wasn't meaningful data. I'm not going to go through sort of the heart of the data. But this was a large retrospective study of over 200 patients that looked at a slightly larger diameter coil to thousands of an inch thicker. Um But they had a 6.5% reduction in recapitalization. You know it's retrospective it's not great quality but I certainly looked promising. Um And there's another one uh study similar that was looking at GdC 18 versus G. D. C. 10 coils and again they saw about a 6% higher packing density and about a 3.3% or 50% relative reduction and recapitalization. Uh And one of the most interesting papers was an animal study. The purpose of the paper. And this is about digging into the literature. The purpose of the paper was to look at coils with little fibers on them versus coils that don't have little fibers. And um but if you looked at the data, what you realized was whether or not they had fibers or not if you had the fatter coils, you had much better occlusion later versus the skinny coils. So they weren't really looking at that. They were looking at whether there was a fiber or not, but it made a difference, interesting side note as well, this is 2000 and eight when this paper came out, I'm a fellow, when I researched, it was probably 2000 and nine or 10, just started my career. The author, quill turk. Um I didn't know who he was at all at the time, he's become one of my closest friends in the field and uh really a very important figure in my life. Um So you've got all this anecdotal evidence, what can you do? There's no high quality evidence. And so that led me, well I'm on a quote kick, so I decided to write this 12 from hypocrisy science is the father of knowledge, but opinion breeds ignorance. So again, don't be judgmental, bi curious, don't feel like you know the answer, but See if you can figure out. And so that led us to come up with feet framing, 18 coils and cerebral aneurysms trial. And I really wanted to highlight this as a starting point of this discussion of wanting to do research because sometimes what I've mentored people over the years and I've talked about doing research in partnership with industry, they have a pre they have a judgmental approach to it to be frank, where they say, well that's all B. S er I don't want to just create marketing data for some company or any number of variations on that, but I want to implore to all of the faculty that might be interested in doing something that's particularly younger guys starting out and girls. Um I don't know if I'm allowed to say guys and girls and the younger people coming out um that you can do really meaningful science in this context and so you don't have to just do a marketing study for a company. And I think that this is an example of doing that. Um I'll never forget. I hashed I made a proposal, turned it in, we went back and forth a bunch and actually hashed out the final details of the funding with the The president of the of the division while on the line for snow white at Disney World with my kids. It was a really long line and we were sitting there and he called and we spent about 10 minutes finalizing that. But but what we, what we came up with was real science prospective randomized trial to evaluate and you stability in the larger versus the smaller coils. Now, what's the win for the company? Well, we're only gonna use one coil on the trial. That's important. Scientifically you don't want to have a lot of variables right in the science of experiment, you keep everything stable and then you change one variable and you see the influence of that. So it's good for the science, frankly, it's also good for the company because now anyone who's interested in this question who participates in this trial is going to be using their product. Um, so you know, you can be realistic about the potential benefits on both sides, but you can still be committed to doing meaningful science. And uh, so that's what we did. And interestingly again, not just shooting from the hip of being really thoughtful, we decided to target mid sized aneurism because it turns out there was another randomized trial that was published just before this. And what they discovered was that with the really small coils, there was no difference between the types of coil. It was a different variants in coils, but basically everything worked really well for the really small aneurysms and nothing worked very well for the really large aneurysms. But the midsized aneurysms in that cohort, they actually saw benefit with their study. And so I thought it made a lot of sense for us to target exactly that population, right. You don't treat, it's like doing an aneurysm trial for subjecting hemorrhage. You don't want to treat all the great fours and fives because there's such a high rate of poor outcomes. You don't want to treat all the ones and twos because there's so many that do well, you really want to target that sweet spot of the threes where you could potentially really affect their outcomes and actually I'm really excited to say that just near the end of last year we completed enrollment. So this is, this is a 10 year labor of love from, you know, inception to making it happen. Um, but we have, we're not waiting for the final follow up pictures one year outcomes of the final outcomes. But we have a 651 patient prospective randomized trial. That's the largest prospective randomized trial. Um, for where everyone got aneurysm treatment that that we have in this context. Um, and so for the field has, so this is exciting and we're going to get some meaningful answers and we're gonna have this massive data set where we can analyze. Like for instance, we are capturing other pieces of information. Did you intend to stand? Did you intend to balloon? Did you actually stand? Did you actually balloon all these other questions? Aneurysm dimensions? Everything's core lab adjudicated. This is going to inform aneurysm care for many years to come, which personally I find excitement exciting. So a second question are actually really a judgmental statement that someone cared for me. Uh, there's a well known neurosurgeon interventionist who is relatively conservative in the way they like to approach things and this person not not here at Sinai or ever here. Um, this person said to me, you can't coil small aneurysms to high risk if you try to put coils into a little aneurysm, it's gonna pop. All those patients have to be sent to surgery. Um, you guys, I think know anecdotally believe that that's not the case, but this is a perfect example where the person didn't want to wonder about it, didn't want to figure it out. They just said I'm not going to do those. I'm gonna refer those all. So that instead we became curious when we designed the trial called coast the coiling of aneurysm smaller than five. It's single arm, but it's all core lab adjudicated. It's all perspective And we've enrolled 300 patients in that trial. In fact, we've, we've just got the last imaging follow up on the last ones and the next few months will be finalizing that data and putting that out there. You know, if you're keeping track that's now 1000 patients with independent high quality prospective Corps lab adjudicated data that we've collected across these two trials just in the last number of years in KhosT took because it was single arm. And um it didn't take nearly as long as I think we finished coast in four years. Um, but there are obviously so many more questions for us to to address right. There are people that say, well, I'm going to follow the guidelines and if you're outside the guidelines then you're wrong, right? And or they're going to people that say, well, I know what's best for my patients even though it's outside the islands. I'm gonna treat this and where this is a very hot topic right now is in stroke thrown back to me, right. Who should we treat. And currently the lay of the land is defined by the american heart and stroke association written guidelines. And if you look at those, this is the statement on the amphetamine who should be treated? There's a couple interesting things about the statement. One as it says patients should receive mechanical thyroidectomy with the stent retriever if they meet the following criteria. Um, I, I think that's a real problem. They later say direct aspirations, lumpectomy um, is recommended as not inferior distant retrievers. So I don't understand why they even continue to pull them apart. It's like arguing whether you wear Nike cleats or Adidas cleats makes a difference in how well you play soccer or something does that affect? Um, so I would strike out calling out any particular technology since it's been proven, I'm happy to say by the way, that was another situation where being curious was helpful. Um, that guy quill turk that I mentioned before that did the aneurysm trial. He called me up one day and said, hey, I was going to do a stent retriever pool with a aspiration catheter behind it, but I couldn't get blood back from the aspiration catheter. So I pulled it out and the clot was in the end of it and the blood vessel was wide open. He's like, you gotta try this. And I said, that sounds ridiculous. And I was like, all right, I'll try it. And I did it and it worked. And so we did a few more to work more and that started the whole adapt or aspiration for throwback to me, aspirations are affecting me. That curiosity. We did a whole bunch of papers, we put it together, we wrote it up as a case series. We then did a multi center case series and then we went and again meaningful science out of partnership with industry. We went to a company that made aspiration catheters and we asked them to fund us to do a high quality, completely independent prospective randomized trial. The company never saw the data until the night before I presented at the international stroke conference. They just gave us the money to the tune of $12 million dollars and we ran this trial. That trial has changed the way thrown back to me is done. Almost everyone does aspiration now as a first line therapy. Um we published the results in Lancet and it was meaningful and so again having that curiosity and looking to find ways to answer that curiosity whether from independent funding or from a partnership with industry or NIH or DARPA whatever you pursue, it's worth doing. But this is the current recommendations. You need to have a pre stroke M. R. S score of 0 to 1, basically have no disability at all, not even minor. Um You need to have uh I Crm one occlusion. You need to have a high and tight stroke scale, you need to have a high aspect scale aspects means that you have very little in part to start with. Um And so let's let's evaluate this. Let's think about this, right? So you start with the first one, pre stroke M. R. S. So what does that mean for those of you that are familiar with the M. R. S. M. R. S. Zero means you have no symptoms, no nothing that bothers you in your life that way, one means you have some symptoms but it doesn't affect you at all. Two means you have some disability, but you're not dependent in any way you can do everything independently. Three means you can still walk around, but you need some help somewhere now. three is a big range. It could be a very minor dependency. You know, someone needs to cut your steak for you or you can't do your, you're older and you're you're not, you're functional and you live independent but you can't really manage your bills anymore. Your daughter helps you with your bills or something like that. Um So there's a big range. So this is effectively saying that unless you're exactly perfect, you shouldn't get a thrown back to me. And obviously that's a problem, right? And people are addressing this and working on it. Here's a paper where looked at populations across to centers that had priests uh stroke disability and evaluated how they did. And it turns out patients did pretty well comparing the patients that had no disability. Of the patients that did. uh in fact 26% of if you had no disability You went from 30 26% good outcome without treatment to 36% with good treatment. Um And when you looked at it in comparison of M. R. S. 0 to 2 or three people with some disability, they had equal benefits. They still benefited in that context. However what was interesting was they did have a much higher mortality. And this has been shown in a lot of studies now. So if you have preexisting disability we can almost certainly you're going to have a better outcome if we do so well over the course of a population there will be better outcomes with lumpectomy relative to know thyroidectomy. But The mortality rate is very high in that population as compared to the modified Rankin 0 to 1 population. Um And uh anyways that's not important. There's anterior circulations. So they do have a follow up caveat of those recommendations that the benefits are uncertain but it may be reasonable to consider treating patients with an M. R. S. Greater than one. But the truth is we need data And so being curious, we're working on that I'm co P. I. A dual pi with Eva. Mystery on a grant called tested for the treatment of endovascular intervention for stroke patients with existing disability. Um And we're going through the quarry process right now to get that funding. Um This isn't kind of exactly what Corey is looking for in terms of population evaluation care. So hopefully that will come through. You know. One of the other things they say is if if you don't have a high and I'd stroke scale, if you're generally functionally okay you shouldn't get an intervention. Right. But the truth is about 30-50% of acute ischemic stroke are people with minor symptoms. So that's you know, I don't know, 3 400,000 people per year. Still almost a quarter of those patients that come with minor stroke symptoms end up with really poor outcomes. Right? And the most critical component is early neurologic deterioration. Where they come in they have a minor stroke and then all of a sudden they go south, they get much worse. And it turns out that have been somewhere around a quarter to almost a half of patients, right? And if that happens you're, The outcome is much much worse. It's almost 60% worse turns out for patients that come in with minor stroke systems that have a large vessel occlusion observed. Then there at over two fold increase of having one of those neurologic early neurologic deterioration and it usually happens within the 1st 24 hours, 5 to 16 hours after showing up. Um Now here's the problem though. If you come in with a minor stroke, two thirds of them don't even get pictures. So we don't even often know if they have that large vessel occlusion. Right? People estimate that it's probably on the order of 70,000 people per year in the US that have minor stroke systems with a large vessel occlusion. 9% in the US think about that. That's a big number. That's double the number of ruptured aneurysms that we see in the United States. Right? What's sort of at the heart of neurosurgical stripper vascular care? If you have a minor stroke system with an L. D. O. You have a seven times increased likelihood of poor outcome compared to if you don't have an LBO okay. And somewhere between a third to half of the patients end up having a poor outcome that come in with a minor stroke About 40% say. So it's not all of them, 60% of them without treatment end up doing okay but 40% do really poorly. That's an issue. Right? How do we what do we do about that? Now? We don't have great data on this because most of the trials both in Hermes as well as the ones that we participated when and and Grace. Um They didn't they excluded patients with low and age because they wanted to be able to make sure they could show a benefit. But for the data we have there is it's not significant but it suggests a almost two full benefit to doing thrown back to me in that patient population, I'm not going to dig through all of these different studies here that but basically these are all people that have looked at exactly this question. We're looking at low NIH patients and this is this this though is worth taking a few seconds on this graph. Because what it shows is if you look at the patients that have a proximal versus distal inclusions, you see a real effect. So if they have a low and I had stroke scale with a proximal occlusion, there's a very, very powerful benefit. They have a lower night stroke scale but it's a distal occlusion. You don't see the same benefit. So again, being curious looking at the different populations saying how can we provide benefits? There's just some more data but it's debated, you know, Jama neurology had a paper published of over 250 patients where they found no benefit doing thrown back to me in that patient population. Right? So maybe it's not a good idea to take these patients and an attempt to reach them and attempted to treat them. Um Now one of the things that we do is we say, well let's wait, let's bring them in with a low night stroke scale and then if they get worse and the ice you will take them. That's obviously fraught with some concerns. I think all of us have had the patient who deteriorated overnight but it wasn't picked up two rounds and such. But ideally that could be a good idea. But it turns out that if you do delayed rescue, there was a paper that suggested that instead of having a 30% good outcome. Um if you did uh If you had to go to rescue it went down to 75%. So we know early needed neurologic curation, associated poor outcome. We know that if you do throw it back to me it prevents the likelihood of having an early neurologic deterioration. We also know that early treatment is better than delayed treatment. Rescue treatment. Um but we also know that when you do intervention it carries a risk right up to 12% risk of bleeding. So is it possible to identify those patients that are going to do worse versus those that won't. Can we find the 40% of patients that have lower night stroke skills and lbos that are gonna end up doing very poorly and can we treat them? And or the alternative is we get to come back to me to be so safe that it makes more sense mathematically to just treat everyone. Don't try to find the specific population but treat as many people as you can that have this presentation. And that's currently debated. This is a publication in H and R. That argued exactly for that point in terms of safety. But the reality is the current recommendation is that it may be reasonable to consider in this patient population and we need that data and we're working on that. So here we are participating in and running a trial called LBO champs. Um Housing is a P. I. For that. And we're also participating in a trial called Ndolo, both of which look at this population. And so we're working to get those answers. But it's not we're not chasing trials. The trials become self evident when you're curious about these questions. Um And one another one of the recommendations that they excluded people with large strokes, large cores if you have a severe stroke already on your cat scan doesn't make sense to return blood flow. Well, it turns out there's a data that suggests that we probably should. This is a study that was published in J. N. I. S. Um that suggested value in that patient population. Here's another paper publication out of France out of there and no vascular registry which showed that this is a little tricky what they said is if you have a low aspects and we treat you if we get your blood vessel open, you do better than if we don't. So that's different than comparing to medical arm. But there's a lot of the way the early stroke trials were done. Um and it's really kind of a proof of concept that there is potential value to opening the blood vessels. Um This is a further paper, out of out of the same french registry that basically demonstrated 4.5 fold improvement in good outcomes. Um And uh and then this is from the select group. This is run by Greg Albers which likewise if you see they took patients that were modified ring inserted to that had big strokes on their first ct And they had over doubled the number of patients that achieved independence um back 0-2 afterwards versus those that did not. So we need better trials. We need our cts to figure this stuff out right there are big systemic meta analyses that do this again. All of them suggest to benefit. So even though the brain is dead, restoring blood flow, helps recovery, helps new pathways develop, helps other ways to make it done. But we need more studies to figure it out. We need data Currently we just have this loose suggestion that it may be reasonable to consider in this population. We're studying this. So we have a trial here at Mount Sinai called laser low aspects stroke and vascular re perfusion where we're enrolling patients randomizing them to figure out does it make sense to treat this patient population? You know, it's funny though we still run against judgmentalism versus being curious, we've had cases where the physician said, well it's a young person. I don't want to not offer them treatments. So we really have to do this and they don't offer the trial. That's dangerous. I think you have to make an honest assessment of whether science provides echo poise and if it does, you have to commit to the echo poise completely and wholeheartedly. So one last one around the stroke side is the guidelines say unless it's in the M. One or the I. C. A. You shouldn't do the lumpectomy. But the truth is the fields already moved out to distal vessels or medium vessels. And in fact one of the questions is what is even a distal vessel if you look at the literature that's out there right now for em to a conclusions, both independent series like this one published by max Smokin and his group or even the efficacy of em to treatment and the Hermes collaboration. So this is five prospective randomized trial with individual patient level data pooled, there's clear benefit for the treatment of em choose. So an M. Two should no longer be considered a distal vessel or questionable treatment. This data is pretty robust and m to inclusion. You see an odds ratio of over two for better outcome. The p value of point oh three um in the Hermes collaborative dataset and in fact this gets worked out and proven no matter how you chop it up, If you say where exactly is the M2, is it a dominant? Ooh is it a non dominant M2. They all show benefit. That's pretty clear. And so when you look at these papers on the interesting conclusions, you got to see how much of them are in twos or how many are really distal. For instance this paper you can see there's only 10% are really truly distal. Everything else is M2s. But in this cohort they saw tremendous good outcomes and improvements. There's now a literature developing around exactly this question. How far out do we go? There are people who are curious that are driving this. This is a little retrospective review that suggested benefit. You can see the clots in very distant locations. Pcs distillation, a distal M. C. A. But they were able to get good reaper fusions, very low complication rates and reasonably get outcomes. This is something to keep in mind right. If we can do it safely. Should we be trying to figure out the best way to do it? Here's a little example of a case here. I think this was caroms case but you can see this is quite distal. But this patient had a profound aphasia and so he was able to go out with a liar. I think this is playing Yeah. Bring a little micro catheter out to that distal location. Right? We're like an M. 45 somewhere right in angular branch and then use that aspiration catheter to restore the blood flow. You can see that the artery is completely opened up there and the patient had complete resolution near complete resolution of the aphasia and resolution of the hemming to legia. So it's reasonable. but we need to figure out better we need better data to understand that all of these things. Medium vessel inclusions, lower night circulatory. These are what we call indication expansions. So the question becomes do we have to do you know 11 thing you might be curious about is do we have to keep doing these one off trials or can we create an infrastructure by which we can do all of these studies And so we're working on that. So there's a thing called stroke net thrown back to the endovascular platform or step um which I am fortunate enough to be able to be a part of as a P. I multiply with Jeff saber and put like a tree and a couple other leaders in stroke field. Um And we're working with the nitric now it's interesting. It's not it's so different as a platform that it's not a typical um council study section type process but there's a there's sort of a separate outside funding process through an R. F. A. Um that we're having weekly meetings for a few hours structuring this, working with the people of D. N. A. H. That are experts in platform trials. So for those of you don't know platform trials have revolutionized cancer therapies and other things. So the idea is you create a Master Protocol and platform where you're collecting data on every patient that gets treated. Um with a given for instance patients with brain G. B. M. S. Or patients with breast cancer or whatever it is. You're collecting all that information and then you layer in specific types of trials within that whole population and patients may get randomized into multiple branches of those various treatments. You pull that data to get to an answer and the first step of that is going to be step stone which is all these indications expansion questions and so hopefully that will come online by the end of this year. Where else is our knowledge lacking? I mean pretty much everywhere particular I ch everyone here is familiar with the amazing work chris has done. Um really typifying and codifying the technology or the technique of scuba using endoscopic ice h evacuation. Now that's exciting. We've refined the technique that I truly believe is transformational and important but is that really enough? And and the answer isn't, you need to be curious and do research and so we're doing a lot of it. Um we just completed enrollment and invest which is a prospective single arm trial of endoscopic evacuation. Um Chris and I have partnered with some colleagues of ours, a guy named Bruce Campbell in Australia and have supported their starting a randomized trial. They're called evacuate. Um Chris is running a trial here in the U. S. A prospective randomized trial called mirror evaluating a particular type of surgery scope, a particular type of endoscope called the surgeon scope um and minute which I'll highlight briefly is a large prospective Randomized NIH trial um that we got extremely favorable scores on last round. And we're submitting again in this next cycle to look at early evacuation less than 12 hours with endoscope scuba technique for I. Ch treatment. It's 231 patients randomized 3 to 1 treatment versus control arm. It's a phase two futility design and we have forced recruitment, just like the Tv T. P. A. Trials that were done in the nineties. We have forced recruitment so that two thirds of the patients are getting get to the O. R. Within less than eight hours. Um so we're gonna be able to first answer is it beneficial within less than 12. If that group shows futility. If we're not able to refute futility, then we're going to look at it in the less than eight our group so it's a pretty neat experience and pretty neat trial. And hopefully we'll get that funding before the end of the year. There's a rich history of evidence based care in vascular neurosurgery, right? We have seven prospective randomized trials for thrown back to me. I was lucky enough to be the P. I. On on therapy. And our group contribute to that Three prospective randomized trials for 12 to 24 hours. Run back to me. We were major contributors leading rollers for positive and I was able to be the P. I. For that study. Um Three ongoing perspective. Our cTS for mm hmm. Though, chris Kellner's driving one of those membrane which you guys may have heard of and we're treating here please. Any of you that have patients with subdural that don't need to urgently go to the or or even if they do touch base with our team and touch base with chris in that capacity the field is replete with high quality evidence generation and I'm really proud that our group is leading in that charge and there's tons more right step and tested and laser and LBO champs things I talked about but also incite a clot atomic study that chris is running a minute. I talked about missed. That Joanna's really it's hard to imagine the level of national international conversation around the mobile stroke thrown back to me that Joanne has caused and driven with her work and missed. And obviously aspiration thrown back to me with compass. There's many more things going on. Um But I would I would counsel that all of these are related to aneurysms and strokes and mobilisations. And this is again, let's be curious. I think we're thinking too small. This is a saying that I've gotten from from Dr. Pedersen not stop thinking small but but don't think small because there's so many bigger things to go and I would highlight interventional cardiology for the very first angioplasty of a cardiac artery was performed in 1977 By the 80s cardiac Argentinia coronary intervention or balloon angioplasty was rampant By the 90s stents have become the standard of care and they're putting steps for about 25 years or so 20 years. That's what interventional cardiology was. It was going in and using a balloon to open up a blocked artery, that was it. But if you look at international cardiology these days, they replace valves, right? They have what's called structural heart. They perforate or close atrial septum. They put plugs into atrial appendage is right or they rewire the heart. They put in electric leads to read and or stimulate, they oblate the circuitry of the heart. Right? So they're they're doing all these different things, structural electrophysiology. Why why can't we be doing those same things? And I think we will many, many of you may know Carl Heimann, he's a chair at Tufts and a friend of mine and a really great guy um He worked with his endovascular partner, Adam Malik. They've developed a trans vascular VP shunt to replace VP shunts basically. They go into the patrol sinus and create a new arachnoid granule ation, a tube that perforated into the CSF space and allows the CSF to drain into the jugular. Um They've done it in four patients in south America with very promising results. It might not be along with just like the cardiologist. Um you know, structurally change the anatomy. We might be doing that in in through the vascular and endovascular. Likewise, you know, a very hot topic is the venus system and the drainage process. Do we restructure? Do we open up closed transverse sinuses? You know Pierre gibbon has been really a revolutionary in terms of driving future therapies is running the river stem trial which is completed enrollment. They don't have all their follow up yet but they've got all their patients enrolled for venous sinus stenting for. Ih right. Is that there's a whole structural component to reworking the anatomy. And what about electrophysiology? Right. Um Here you guys are a little more familiar than other places but we're doing that too. Right. Tom Oxley is leading the charge with synchrotron, trans vascular brain computer interface, both recording and stimulating. Um It won't be alone until we're doing all of these things. I think that cerebral vascular neurosurgery, if we remain curious, the future is going to be much much bigger than the past. And that gets me pretty darn excited. I think in general for neurosurgery for each of you in each of your fields, the future is wide open. If you maintain that curiosity and you want to go after those questions there's so much you can do and I'm happy to say that much of it's being led by the younger generation is a picture at the senior society right in the front we've got Sinai or Sinai team with chris Keller and Justin mus italy. Um So I'm very excited about it. Thank you for taking the time to listen to me and happy to take any questions. Thank you J that was inspiring. Beautiful. Any comments questions I think people are blown away. Hey jay awesome talk man, I'm really inspiring and thank you for giving that to you. The things that I've appreciated with what you've done and others is is you've taken an area in neurosurgery to another level for But number two you've kept it under the auspice leadership of neurosurgery. So where am I going with this? How many times do we talk about areas in neurosurgery? We've lost right, we've lost other specialties, we haven't led them correctly. We published outcome studies and you know I think well today in your grand round stock is that you know with with management of stroke and other cerebrovascular disorders and then other ideas and concepts to take it to the next level that eating the charge and I think you know that that's an important concept that I'd love to, you know briefly speak about. I'm sorry I just don't know if I totally get it. So you're saying in terms of leading the charge as a neurosurgical community? Yeah just you know some of these areas of neurosurgery in terms of management of stroke have always been non neurosurgery right and now you know neurosurgery is kind of neat in this whole story. I I think so I have two thoughts on that. Okay, the first one is I mean go back to ted lasso, I mean I think one of the biggest problems with neurosurgeons were too damn judgmental. That's my honest opinion. I think that that as a field we we we tend to say it was one of my real bugaboos, we we go around and say oh this is the way it's done, this is the way it should be, this is the only o instead showed you can't treat I ch can't do that, No. Now every patient's gonna not be treated and just die, like it's judgmentalism versus saying well okay look, don't just go crazy land, but in a rigorous way, let's start answering questions and figuring it out and you're right, look, there's no question in my career has benefited in that I and I was I was actually giving this advice to somebody last night um it's worth looking for the areas where there are real questions, even if everyone in your field says, oh that's not neurosurgical. I remember early in my career I got made fun of for, you know, Clot chaser, like why are you, why are you pursuing, you know uh stroke? You know, that's not that's not neurosurgical, you know? It is and you know what nick used to tell me stories about when he started his career, he'd get up to give a talk at W and S in the front row, all the senior neurosurgery guys took out newspapers and like opened them and like read them on purpose like to insult him as he was, you know, giving his talk that it was not neurosurgery. I had a very famous chairman who's retired now in uh in new york um literally like laugh about how endovascular wasn't neurosurgery when I was like looking at what I wanted to do for my career's so, so part of it is not being judgmental and looking into those areas and like thinking about what you can do, look what Doug has done pursuing radiosurgery, right or Isabel. You know, there's so many people that have done like tremendous things. Um you know, it's it's just you, it's very easy to just think, oh, I'm going to make fun of that or I'm not going to be interested in that or or or you know, carry those, those sort of judgmental glasses on and I think if we can shed them, I think it's important. And the other part of my answer, I said I had two parts is is um I think it's I think the world can use us. I think neurosurgeons as a general rule, have a great work ethic. Our our intents were well situated to do these sorts of projects and research um because what we do clinically generates good revenue. We're not like worried that we're going to get fired if we don't have our next grant to support our salary. Um as is often the case for for medical specialty researchers. Um I think we're really well positioned to do some of the most exploratory and creative work that exists and so I think it should be done uh and and we we should bring it to the rest of world. And many of my closest friends are not in our surgeons that have the same attitude, they're doing the same things. Radiologists, neurologists. I think there's room for everyone as long as we're all curious enough and working to make it better. Thank you jay. I think in addition to reaching out to other fields, the I. C. H. Program has exemplified that all of us of a certain age were raised realistically about it's just really nothing there to do. Um And by asking the questions that you've asked and focusing everything in one location and then convincing a talented young person to join you with this. I think you're making progress in what is now a neurosurgical disease that we really had given up on. So it's very inspirational and also it looks like a lot of fun right? It's not just hard, it's a blast it really is. I read. I read a quote and I'm not gonna remember who said it right now but I read a quote about someone like talking about being in the lab and and researching something and figuring something out and when they figure that thing out and you get your results if you're the only person in the world that knows that it's pretty cool like you've you've contributed you're you're going to contribute a piece of knowledge is going to change how things are done in some level. And that's what I feel about the clinical research. Like when we first run the first numbers we lock the dataset and you run the numbers and you get those back and you say holy crap aspiration really works. This is awesome. And you know it's going to impact lots of lives uh way more than you could ever touch with your own hands. It's really fun. Oh any other comments for questions from the group? All right thank you. That was wonderful. We do we do have a few questions in the Q. And a box. Sorry about that. Just blowing them up later. We have L. D. I think he meant L. V. O. Um He actually wrote. Okay I see I see you already you already answered that one. It says uh what's the quick screen in the office for a patient who you suspect might have a large vessel occlusion and minimal neurologic signs. C. T. A. Is the answer there. Um And then we've got a longer question here. It's about following up on research. Maybe send an email if you can and we can do that offline. Okay. I see and then a comment. Alright. Alright. Alright guys. Alright thanks everyone. Thanks everybody