Dr. Woo Song Do - From Battlefield to Bench to Bedside and Back

All right, good morning everyone. Welcome to pediatric surgery Grand Rounds. It is my distinct honor and pleasure to introduce someone today who needs no introduction among this audience, Dr. Wu Do. I don't want to spend a lot of time introducing him because we all know him very well. He was our previous pediatric surgery fellow here. Since leaving here, Wu's had a really impressive career, which surprises no one in his short time. Since he's left, he's the, as you can see, the chief of pediatric surgery at the Walter Reed Medical Center. He is also has a really impressive distinction of being one of few pediatric surgeons who has been deployed to the Middle East and for that we're very grateful. He has also done a great deal of research, getting involved very quickly in research on limb perfusion as well as hemorrhage control through military grant funding through which he's already had a lot of great success. And I think we'll learn a little bit about that today. As one of his predecessors, Wu's shadow is cast broad here at BCH. So I won't spend a lot more time talking about him because you don't want to hear from me, you want to hear from him. So without further ado, Dr. Wu Do. Thanks Brian for the kind intro. While it's really good to be back, it feels like a homecoming to me and it's just so awesome to see everyone in the audience. Thank you so much for making the time to come out. And thanks for this incredible privilege to come back. When Brian invited me, I was joking with him that this might have to be a grandbrowns with the little G because I don't know that I've accomplished quite enough yet to be worthy of this distinction. But I'd love to show you what I've been able to take from my training here so far and maybe shed some light on some areas where we can collaborate between Boston Children's and the military and make some really impressive progress going forward. So with that, we'll get started. So I have no disclosures. I am obligated to show the standard military disclaimer that these are my views alone. I'd love to start with a story that matters deeply to me and how this all connects to the way I trained, my deployment, and bringing all that experience back to the bench with the hope that we might be able to make some translational research efforts that go on to help patients. As one of my mentors here said, it's about solving a vaccine clinical conundrum. And so I'm going to show off a little bit about what we've been able to accomplish in the battlefield shock organ support lab and primarily use ex-singuination cardiac arrest as the idea behind reversing irreversible shock. And if time allows, we'll get into a little bit more about ischemia reprefusion as well as some of the extra corporeal limbs salvage strategies. So this is me when I was a lot younger. I joined the Army when I was 18 because I believed in the American dream. My parents had raised me to take great pride in enduring sacrifice. They showed me by personal example. And so it was no surprise when I fell in love with the ideals of West Point, duty-honored country, and I believed deeply, I bought into it heavily. I guess we're all romantic when we start off, right? Like I see a lot of young people in the audience. And over time, I think we get a little bit more jaded. This was me back when I started and I try not to forget these roots because as I was going through my early Army career, I knew that I wanted to become a doctor. It's just I thought that going to West Point and learning how to be a leader first would set the foundation for me to be a doctor in the right way. And it was in doing so that I encountered this man, Nick Vote. He was in the year group ahead of me, also very interested in becoming a doctor. He had a different strategy because most of us who went to West Point tried to go straight through like I did, meaning go through four years of West Point, get into a great medical school, and keep chugging along. Well, Nick's perspective was he wanted to go into the infantry, which is a pretty competitive thing to do. He wanted to go into the infantry, you know, complete Ranger school, which is not for the weaker faint hearted, learn what it's like to be a soldier and then come back and be a doctor. I admired that about him. So Nick did all that and I remember I was just across the street doing, I don't know, living my comfortable life as a Harvard medical student in my first year. And I got news that Nick was involved in an IED explosion. You see this headline from the military times, Lieutenant Journeys Back from the Dead, held more than 300 troops rallied to save one soldier. So Nick was involved in this explosion. Immediately, the people around him started these maneuvers, including early turnickets, crack with their anatomy, sternolio. We don't use hex send anymore, but that was part of the algorithm then. He went into cardiac arrest five times. He got a early resuscitated for economy and just in the immediate outset, he had 400 four unit supply products that were utilized. And with that heroic effort, taking him from that initial point of injury all the way through Kandahar to Poggram, to Lanch School, to Walter Reed where I am now, he had over 30 operations with 100 additional unit supply products, endured multiple complications, including an aneurysm requiring brain surgery. But he survived. With all this heroic effort, Nick Vogue was able to go and live a healthy life again. And he is quoted as saying, I like to say that I'm now truly multinational and multi-service after having received multiple blood volumes of transfusion over. And this story had a deep impact on me as I was going through medical school on my early stages of training. How can you not get romantic about surgery? I think we all need to be able to kind of look into our why, why we go through all of this effort. And for me, this is why I started the whole process. And so with that background, if we look at the intersection between surgery as a whole and war, we know that there's a lot of overlap. But I was just deployed and I deployed with a lot of people who don't actually, they straight up asked me what the word pediatric means. The connection is not quite as robust as you might see here. And they're really great individuals, right? But they might not see immediately at the outset what the overlap between pediatric surgery and war is. But I think all of us here would. And that's what the first part of my talk is going to be about. So as I went through training, I had this kind of sycophine task looming over my head. But I'd be able to save the next Nick that came my way. I knew that I was going to have to go to war. And I feel really lucky and blessed and grateful that you all here were willing to take a chance on me and to train me to get me ready to go. So I love this cartoon from the New Yorker because it shows sycophysies trying to perform all of his insurmountable tasks. He has the weight of the boulder that he's trying to move. And in the background, there's this quip. Hey, sycophys, when you've got a minute, I'd like to discuss this progress report with you. It's a little bit ingest. I swear, Dr. Modi, this is not you quipping at me about whether I completed my progress reports. People like Dr. Modi were pushing the boulder right there with me, helping make sure I got good training to be able to then apply the lessons from Boston Children's in wartime. And I'm so grateful for that because when I went, it was very clear to me that the training I endured here set me up to be maximally successful on deployment, even though the deployment was not about pediatric surgery. So here on the left, I'm directing the team as we're going through a mass casualty exercise. You can see me also actively trying to grow a ugly mustache. It didn't work so well. On the right, this is our forward surgical team operating on an extremity, revascularizing. You can see that the space is quite cramped. It's certainly not optimal conditions. It's quite an austere circumstance. You don't learn to do that here at Boston Children's, right? Here's me doing a craniectomy with a conventional drill because the drill we had was not sufficient to get this skull decompressed in time, right? You don't learn to do this as a pediatric surgeon of Boston Children's. What you do learn is just so much more valuable to be applied and translated to the austereist of circumstances to the most dire of circumstances because we live it every day here. And so what may initially seem like a wide gap between war and pediatric surgery, I think I've come to see you through personal experience that war and the pediatric surgeon are quite connected. And here at Boston Children's, you guys have showed me time and time again about the deep personal connection to the consequences of death and destruction. And I look in the audience here and just every attending that I see, I can just name this pop in my mind of all the patients we took care of together and like we had some big wins. And those wins and losses all stick with us. I'd love to share a quote by Dr. Pewter. So this was after he had received a promising investigator award and then was asked to reflect on 10 years of experience. And he said, I saw firsthand how the death of a child can destroy a family. And this was in speaking about intestinal failure associated liver disease. This motivated me to help this vulnerable group. It was a slow death and we became attached to the families and staff who were dealing with this on a daily basis. What's crazy to me now is that we may have a generation of trainees that come through the system and actually never see how bad this is. So in one lifetime through monumental effort where Dr. Pewter is just the one being quoted, right, it's an entire system that came out of here that was able to make such a generational impact. And he goes on to say future academic surgeons must learn that the path to solving a vaccine clinical conendrum is never easy or quick and often becomes a soul searching process knowing that our patients and their families count on us to put our best efforts towards solving a problem either in the lab or at the bedside must always be the ultimate motivating factor. And this to me is like the perfect way to capture what I hope the rest of my career will be about. So if we talk about solving vaccine clinical conendrums, at least for me in what I saw on deployment, a large part of it is about traumatic cardiac arrest. So ex-inquination that leads to cardiac arrest. But if we look at the overlap between wartime and pediatric surgery, think about all the ischemia reperfusion issues we deal with in pediatric. Think about all the states of quote irreversible shock where the patient dies. You have a morning grieving family and you're left to wonder if you could have done more and maybe you sleep better at night, you know, believing that you did everything by the book and this was, it was too big of a gap to overcome. It was irreversible. There are so many patients like that. And I don't know. For me, I still remember those patients and I guess I don't just go to sleep so easy on those and it's really made me think a lot about how we do reverse that. So here's an example from Boston Children's. Again, dealing with ischemia reperfusion. What better model is there than midget volvulus? So this child came in with a pH of 6.4 and a lactate of 22 and had dead gut. You know, is this irreversible? Is this insurmountable? Well, I was so lucky to train at a place where through heroic efforts, we now have a child who is beloved and thriving. You know, the entire care team and the system built around this, Dr. Mohammed. All the efforts that Dr. Puter and team laid the groundwork for with the research in the OmegaVen. This child is thriving now. So I think it was important for me before I went off to war to realize what a system of training at Boston Children's does. So now that I am in the lab, this is called the Battlefield Shock Organ Support Program. And there are several lines of effort, but you know, there's a lot of overlap with pediatrics, maybe not extinguination shock, but certainly ischemia, organ failure, ECLS, there's a lot of overlap. And so for me, it was a great way to transition into the lab effort, but in a way where I was able to align with DOD interests to find ways we can make pediatric surgery applicable. So I'd like to move on to this problem about extinguination cardiac arrest. And this was not at my forward surgical team, but throughout the deployment, we actually have tight communications with all other deployed surgeons. And we're helping each other out kind of communicating throughout the process. And one of my friends, we see the patient who 30 minutes prior to coming had a GSW to the right post-year thorax. On arrival, he had carotid pulses that were present. He was hypothermic, tachycardic, had a thready blood pressure. He was intubated. He went into PA arrest, and so CPR was started. And here is his initial labs. PHF 6.8, PCO2 of 65, PO2 of 47, based episode 22, by Carby Levin, hypercalemia, it's at 7.6, his calcium is low at 0.56, he's hyperglycemac, or the HNH of 10.5 and 31. And so I would ask the audience, if a patient like this arrests, and they've been extinguinated, and that's the cause of their arrest, is that survivable. This patient actually died, and it was despite great effort. So two minutes in, he had a thoracotomy, his chest was full of blood. 13 minutes into the cross clamp, he had an anatomic wedged reception, he had an exploratory laparotomy, and there was no bleeding in the abdomen. They sustained the effort for 44 minutes, had rosked twice, PA arrest, a third time, and couldn't get the patient back. And they used all the modern resuscitation strategies we teach now in 2025, right? Low-tider O-hole blood, that's available, a walking blood bank that you can activate. TXA, that's given calcium, and minimizing crystal oids. So despite all these modern strategies, can't save the patient. And this is so frustrating. So with that, if we look back at, you know, where have we come? Because this is different than omega-ven, omega-ven, and intestinal failure, so should liver disease, like horrific deaths, right? Once thought to be insurmountable, I think this is kind of like that. So if we look back, past 25 years from 2000, do you guys know who the fellows were then? So in 2001, we had Dr. Papa DocuSynfuter. In 2002, we had Dr. H.B. Kim. So in 2000, what literature do you think they were being shown about the outcomes after ED third economy? So it was cited at the time to be 7.4% survival. A lot of time has passed since then. So 25 years, 50 years since the first of the studies that were cited in that 7.4% survival. And not just that, we're looking at a group that has pushed ED thoracotomy as far forward, pre-hospital, right? And so if you do it for patients that undergo traumatic cardiac arrest, how many of them get back? What's the survival? And as you might suspect, cardiac tamponod treated within 10 to 15 minutes is going to be the best odds of survival, right here on the left. On the right, for ex-sanguination, though, like if you do it immediately, maybe it's highest 10% predicted probability, but your odds are very low. And what I like about this study is they followed the patients out to longer term outcomes. And so if we just look at ex-sanguination, again, ignoring cardiac tamponod, just look at patients that ex-sanguinated and went into arrest. There are such a few, a small subset of patients that actually survive with a favorable neurologic outcome in 2025, with ED thoracotomy pushed to the field. I don't know that you can get any better than that, with the current strategy, 1.6% survival. It harkens back to this study or this commentary that Dr. Blackborne and the military community provided back at the height of the global war and terror, Iraq, Afghanistan timeframe. And they provided an example of a patient who had near-ex-sanguination. Their volume of resuscitation was far greater than the volume of hemorrhage, and despite achieving adequate circulating blood volume indicators of improving physiology, the patient still dies, very frustrating. So this is the vexing clinical conundrum, ex-sanguination cardiac arrest. And how would you study this? For us, we're trying to do it in the lab. It's with a swine model. We do it the oacotomy, neck dissection. We put probes to measure flow in the LAD and the common crowded artery. And then if you control hemorrhage to the point of arrest, for this study, the parameters were map of less than 20, and title of less than 10, you bleed them out over 20 minutes. And usually the blood volume, it takes to achieve cardiac arrest from ex-sanguination in this group of animals, was 54% on a mean of their total blood volume, estimated blood volume. We maintain cardiac arrest for 10 minutes. It's a terrible, terrible period of time, while you're just waiting there to try to do something. And you watch. And then at 10 minutes, you start whatever the intervention is. And for this, for the controls, we said that was starting to give blood back, meaning throughout the transfusion period, we replaced all the shed blood that was lost. We wanted to take the volume of blood loss out of the equation. And then we do the conventional resuscitative thoracotomy. We put a cross-climepondiota, open cardiac massage, 100% F-I-O-2, as you might see in the ER. OK. All these pigs are initially in PEA. If they come back in about 23 minutes, they get rosk, then they have V-Fib, then they die by 75 minutes. And this is a shocking. And you can see the V-Fib continuing. I want to call a timeout here because for me, this was perplexing. I think anytime you see things that are a little contrary to what's taught in the textbooks or in ATLS or whatever, raises some questions. And it made me think, gosh, I did a lot of ED thoracotomies in residency. You're right. A lot of them, once you start reproducing them, they go into Fib. And so it made us think, what's the terminal rhythm of exceingination cardiac arrest? And if you look back in the literature, this is a review that was done by one of our colleagues, not yet published, but historically, it was taught that it was a Sicilian PEA predominantly. It still taught that way in at most places. But perhaps with modern era point of care ultrasound, it might not be that high. It might actually be that the diagnosis is being miscategorized, that a lot of these patients are actually in FI and V-Fib. And this is a different set of animals, different protocol that I won't have time to go in great detail today. But after we started seeing some of these in the former set of experiments, we wanted to extend the arrest period to be able to just define what exactly is the terminal rhythm. And so this is a separate model, hemorrhagic shock plus partial air occlusion. So an ischemia reprefusion model where the animals had uncontrolled hemorrhagic of 30 to 40 percent estimated blood volume, whether it was carotid or liver, a zone 1 partial riboa maintaining a distal map of 20 to 30 at the femoral artery. And if you watch these animals, they go from sinus attack to V-TAC to V-Fib, and then in 35 minutes roughly, they go into acestally. And the reason that matters, it's different than what we've been taught, or at least what I've been taught. But V-Fib, I think, takes on a different strategy than PEA in acestally. And so we have stuff like the arrest trial now. This was published in 2020 for medical cardiac arrest in real-life patients who came in without a hospital cardiac arrest, considered to be from refractory V-Fib. And the question was, does ECPR, compared to conventional CPR have superior outcomes? And the patients that underwent ECPR had such a better intact neurological survival, 43 percent versus 7 percent, that they stopped the study early. For patients that were out of hospital, they reported that the time to getting on ECMO was roughly about 60 minutes. I think that challenges what's possible for patients that are in V-Fib. And so if ECPR works in disease hearts, can it work in recently healthy hearts? So in this video, I apologize. So this video is not going to show. Let's see if this one shows. So this is an ECMO circuit. We do have a reservoir attached to this one. I want to highlight that this is VA ECMO through the groin and just note dark blood in, dark blood out. We have very low FIO2. No added oxygen in the circuit. These animals, it was again a painful 10 minute weight while you're waiting for the animal and wondering if they're going to come back. And then we put them on ECMO and we get them back. This ACT, it's an acronym that we've for vascular surgery reasons more than true like nomenclature reasons, has been dubbed aortic cardiocropylmonary resuscitation and trauma. That's our ECMO group with graded FIO2 escalation compared to the controls looking at survival. And there was a dramatic difference. Whereas all of the animals that underwent conventional resuscitative thoracotomy techniques with 100% FIO2 died before 75 minutes, we got uniform 100% survival in the six animals that had ECMO. When we are measuring the coronary blood flow, we think this is part of the driver is that you can sustain coronary artery blood flow in the ECMO group much better than you can in the control arm. And not just the coronaries, sorry, not just the LAD, but the carotid flow seems to be significantly improved as well. And if you look at the actual electrophysiology of the heart and this v-fib that we were trying to define, if 100% of the controls developed v-fib during the resuscitation period, only a third of the animals underwent v-fib in the ECMO arm. And for those in the ECMO arm, the v-fib was correctable. Whereas in the controls, we couldn't get them back, it was refractory. It was a mean of 2.5 shocks. We looked at all sorts of different physiologic parameters. And these two stood out to me as very interesting. So PIO2, if you imagine like you have a control arm, this patient has arrested, you cross clamp the aorta, you blast them with 100% FIO2. It's no surprise that your PIO2 is going to be super physiologic. And there's certainly literature coming out within the last 5, 10 years, certainly more within the last 1 to 2 years, even in the pediatric surgical community, specifically with CDH and ECMO patients, about hyperoxia being deleterious. You know, perhaps the not just the option for your radicals, but the option being necessary for cellular death. And I think this might be one of the driving factors that is certainly intervenable, because we can tightly control this. And I think it also calls the question, how high you need the oxygen to be. Separately, if you look at pH, right, because it's driven into us that acidosis is part of this lethal triad, at least for trauma patients, the pH was no different between 100% death within the control arm and 100% survival within the ECMO arm, the treatment arm. And so maybe we're placing emphasis on the wrong value. Maybe we are getting fixated on pH and acidosis when, in fact, it's actually not all that relevant. You know, certainly, I don't mean to say it's not relevant at all. It's something we'll follow and it's something that certainly needs to be corrected for the animal to then, or patient in the future to then survive. But during the resuscitation phase, maybe we shouldn't fixate on pH so much. We then looked at the histology of the brain tissue, and these are just some representative examples. And structurally, again, this is imperfect, right, because there's nothing better than waking up the subject and seeing neurologic function, right? It's just a little bit too early for us to be able to do that ethically. But for whatever surrogates we can use right now in the lab on Necropsy with histology, it looks like there's no neuronal loss. Interestingly, there are increased astrocytes. There are markers of pro-inflammatory cytokines, but no evidence of what drives macrophage activation or cell morphology change. At least at a histology level for these animals that go on death within a 75 minute timeframe. Could it look different if you have a patient who you get to survive? And they're on the circuit, and they have questionable neurologic status, but you're just prolonging their life with support. In this current subset of animals, we haven't experienced that to be able to say what histology and what true function would look like in that subset. But again, in this limited sample, I think this is interesting for us to be able to, to the best of our ability, at least consider the neurologic question. So where do we go from here? I think there are a lot of, this is very early, this effort is very early. There are a lot of things that are happening concurrently, even this week. One of the things that we're looking at always, this talk is about taking things from the battlefield to the bench to the bedside and back, back to the battlefield. Like can we get solutions like this to be modular enough, to be deployable? We have examples of ECMO that has been used in the battlefield ECMO circuits that are flown in the air and get patients back through some of these heroic means. But can we make it more feasible? That's one of the things we're currently testing. This is interesting, this next point about what we can do in the pre-deployment setting. I think as we gain more insight into what exactly are the intervenable targets of ischemia reprefusion. Perhaps there will be, there's this holy grail in the trauma community about a trauma vaccine or a cocktail you can give to an acutely injured patient or just before they go on a mission, just in case they do encounter exanguination. We're far away from that, but I think we're gaining insights and actively searching for targets that we can use to mitigate ischemia reprefusion. And I think based on our experience here at Boston Children's with the robust subset of non-traumatic ischemia reprefusion we have, that there could be opportunities to learn. Additionally, we're looking at different resuscitation strategies, specifically how do you refuse? What goes in the pre-fuse rate? I think those are going to be things that have an impact in the longer run. It's not just going to be about the oxygen, but it's going to be about many other factors that go into the pre-fusion. And I see Dr. Laskis and Dr. Dickey in the back, this is why we perseverate on the ICU. Right? That ICU rounds aren't just a one hour affair. It keeps you up the whole day. And I think that's going to be the challenge with how to come up with a good protocol that actually accomplishes some of these things. And the nice thing is, in the lab, we can test various protocols. We're also searching for novel therapeutics. We have some already in the pipeline. We're borrowing from other disciplines, namely transplant, as well as people in the mitochondrial resuscitation field, cardiac surgeons, and people who have experience with inline circuit therapies like nephrologists. So we'll see what those sorts of novel therapeutics, if applied to circuits, can actually help mitigate some of this is chemic refusion. And then for me, I showed that example of the patient I encountered here. I truly think that the overlap that is underappreciated in the adult realm is how perfect of an example of ischemia refusion, the midget volubulose is. And what's crazy is that here at Boston Children's and across many centers, you will have patients routinely who have had a terrible midget volubulose event who have taken out their entire midget and you've resected it in the OR, and you keep them in a silo. In very abdominal closure, you resuscitate them, you go through all that physiology and you get them back. Routinely, we see that happen. And I think in the adult realm, actually, so I wanted to clarify. So in the adult realm, what's different is most people will resect early. So if you have nichrotic bowel, they will uniformly resect early. But here in pediatric surgery, we see the rare examples in this field where you leave dead gut inside to and run through the whole gamut of the ischemia refusion pathway. And then you do the resection later to try to save as much of the gut as possible. And so I think clinically speaking, this is a very unique subset of patients that we can study. And then certainly in the lab, developing a mid-gut ischemia refusion model is going to help translate to, I think, a great partnership. To give an example of one of the products we're actively testing right now, looking at the portability of ECMO. This is the MoVie box. Very small profile. It's designed off of the structure of a vad. So the septum actually bows in and out within the chamber. And utilizing this, we were able to achieve pretty similar results in a pilot. So this is going to be showcased soon within the special operations, military assembly, but I think it's promising that, and the reason I think it works to be honest is because when I showed that video of the ECMO, we were only flowing at 10 to 15 per kilo. And that's low flow and the heart came back. And I think if we rethink VA ECMO for certain situations to be not necessarily about taking over the entire circulation and the entire function of the heart, and you only need to flow lower, I think that opens up a lot of doors for restrictions to cannula size, restrictions to the power of the pump, and the modularity of the pump. So again, these are things best tested in the lab, not directly on patients first, but can perhaps be translatable in the future. Looking at various resuscitation strategies, the next group of experiments that we have coming, we're partnering with a group out of Germany. They've published a lot on what they called controlled automated repriffusion of the whole body or carl. We've taken this strategy actually to the field in real human beings, but for medical, cardiac arrest, and we're curious to test some of the general principles that go beyond behind a pump like this. And so this is the type of pump that stresses some parameters that are different than what we traditionally do. This is a pump that stresses pulsed-towel flow. They are targeting a pH of less than 7.25. They are keeping PAO2 in the 100 to 200 range. Again, really stressing that they're not going super-oxic. Interestingly enough, if the patients are in fib, they actually allow for potassium to rise with thought that it can have some cardioplegic effect. They don't chase calcium levels. They let it below. And they actually drive up osmolarity in the blood, osmolarity, thinking that it might decrease the cerebral edema in might decrease the vasopressor requirements. And then above all, I think perhaps one of the biggest contributing factors is they cool the patients. So their body temperature is 32 to 33 degrees. Which of these factors plays the biggest role? I think it's really hard to say. But it's promising what they've been able to achieve in the field for non-hemorrhagic, non-traumatic medical cardiac arrest in human beings. So we wonder if we can adopt some of those strategies in a pump for a patient who has undergone ex-singurinated cardiac arrest and has a survival of 1 to 2 percent in the way we've done things for 50 years. Can this be the next paradigm shift? So that's what excites me about doing everything from seeing a problem on the battlefield, taking all the lessons you guys taught me about bedside work here at Boston Children's, bringing that all back to the lab and seeing if we can then make that impact felt by the patient again. So thank you so much for allowing me to come here. And Beth is here in the audience. Thank you so much for all your support. This is certainly not possible without you in the background. Thank you to my battlefield shock organ support teammates. All the sessions we've had just kind of mocking up what we plan to do and then the folks that I deployed with, this is all impossible without any of you. So thanks again for this opportunity to speak and I'll open it back up to the fore. Appreciate it. Well, to both of you, welcome home. We're thrilled to have you on the podium and I think there's some people who were thrilled that you'll be back soon again to join the team on the floors and the O.R. and the emergency room and everybody loves that opportunity to have you back and afraid with us when your service allows and we're thrilled with that opportunity. And as you were describing this sort of battlefield, the bench to clinical experience, I was thinking back to when I was training and despite the fact that now we say that certainly training back then was brutal and humane, the people who trained us said, you guys are just like coming in here on skillful time and you'll never have the surgical training that we had in Vietnam, right? And that everything, all the principles that they learned came from the battlefield. And we were all kind of glad that we didn't have that experience for the most part. Maybe a little jealous of having had the experience but not maybe doing the experience. So for those of you who choose to do that, it's just the highest level of equipment and service. And they didn't have, you know, basketball surgery and existence, but they also didn't have the scientific opportunities and sort of the back home laboratory opportunities that you have now and you're taking that to the next level. I'm going to, for specific questions, we'll open up to the rest of the audience and then I'd love to hear about your perspective on that after questions and how we can all learn from that together. Absolutely. I always have trouble when a military officer calls me sir. And I spent two years telling what would stop calling me sir but it doesn't seem to be working. Questions, comments? So Wu. So Wu, thank you for a fantastic talk. The question I had for you just based on your data. Do you think it's a mistake for us to give our patients high oxygen immediately when they're in shock? I think there is more and more evidence emerging that superphysiologic levels of oxygen are quite deleterious. I think we in the pediatric and certainly the neonatal communities have seen effects of that. But interestingly enough, like medicine as we see is very siloed and there's not a lot of crosstalk between communities. I think we can learn a lot from each other because if you talk to the perfusionists, if you talk to the cardiac surgeons, if you talk to the neonatologists, if you talk to us pediatric surgeons, we all have very differing examples of exactly how high and how fast you should go with the oxygen. You speak with intensivists who are around the ECMO circuits all day. They have opinions on this, right? But then does that get translated to the adult trauma surgeon? No. Right? And so when I first joined this lab, there was a lot of, wow, you guys do it that way? That's fascinating. Tell me why. And perhaps one of the valuable traits of after having trained at a dedicated children's hospital that is capable of achieving so much to then going to a place where I'm the only pediatric surgeon, but I'm surrounded by a really smart colleagues across disciplines. I think it's been really eye-opening to me and hopefully to them to have some of this crosstalk. I think we see more and more evidence playing out in the literature about that exact question about the oxygen. I think we will see more and more as we start to do strategies that bring down the oxygen level and see better outcomes. Thank you. Yeah. Well, this is, this was a fascinating overview of both the work and your personal journey in a way. My question is related to the previous one. Can you share how that insight of keeping the oxygen low was reached? Was it serendipitous or you guys are playing with different settings on the ECMO and you show the dark blood coming in, but is there easy as you know to play with different settings? How did it come about? I think a priori we always wanted this to be something that did not hit super physiologic levels of oxygen. I don't have it in this slide deck, but we had so many examples of patients, primarily like adult patients at Shocktrauma, where we partner with where a patient goes on ECMO. Or they do these clinical trials for suspended animation and seeing how the things that are actually problematic at the bedside in those patients. And if you go straight up to high oxygen, these patients end up having a lot of problems. They would show us pictures of PO2 at arrival being 40s, 50s, and then PO2 being 500. And then they would have all sorts of complications or they would have bad cerebral edema and be not survivable. And then you see like literature come out in the CDH community for us as pediatric surgeons about how superoxy is quite deleterious. I think mechanically it makes sense. And so it made us want to start low. We also saw the Carl people's work, right? And the Carl folks in Germany really stressed the not pushing oxygen too high too fast. But for our control arm, we wanted to treat the animals like real human beings get treated when they hit the ER. I do think the oxygen piece is going to be a dogmatic thing that's going to be really challenging to overcome. Even for our patients where like a surgeon is at the bedside and trying to tightly control oxygen, they get handed over to our anesthesia colleagues who are doing their best and using their best techniques too. But there's just this desire to just put them on 100% of our tune. When you look back, it's actually hard to ascertain how much time patients who went into the OR actually spent at super physiologic oxygen levels because they tend to go on the anesthesia circuit and get the oxygen put up. Maybe not for the patients from our NICU that get transported over and we're tightly controlling. But certainly for the MIGUAT Volvulus patients who then get taken to the OR, usually they're starting out at really high oxygen levels. So we wanted to at least mimic that for the control arm. But for the treatment arm, a priori, we knew we wanted to scale up the oxygen. Thank you so much for this great talk. I'm curious if you could speak a little bit to the military adaptation model. And yes, because this is just a behemoth of a structure, it's not one hospital. When you're translating this from your animal models to being used in the field, is this something where you consider partnering with a hospital on the US side where you're going to do something local and controlled in a small trauma center, not small, but trauma relative to the battlefield? Or is this something where there's a more formal process within the military to scale something up? I think you spoke to two things that are near and dear to my heart. One is the civil military partnerships. And I think there's more and more of that these days. I think we're a shining example of one. And across the country, there are more civilian institutions that are willing to take on military partners. And I'm not saying that necessarily means that I come to Dr. Zeleskis or Dr. Duky and say, hey, I have this pump. Can we put the next patient on this pump? It's not quite that simple, right? In the military side, we also ethically shouldn't do it that way either. So the pipeline, I think, is rigorous on both counts. But through civil military partnerships, we have one avenue of actually investigating these questions together, right, which independently should undergo their own rigorous process before being institutionalized. And then on the military, I think we've learned a lot from past wars that we need to have a durability of whatever we learned, the lessons learned of war, and they should not be forgotten before the next war. And so for us, that's called the JTS or joint theater system, joint trauma system. And there is basically a weekly meeting. And at these meetings, these sorts of topics come up, progress updates on these sorts of projects come up, and it drives further innovation. At the bedside, I would say, where is this going to be translated first? I think that's really hard to say. But sometimes if we have enough information to say something is safe, and we're in a situation where there is no other option, I'd say the military is a place that is probably a bit more willing to allow for a heroic attempt. I'm not sure if that makes sense, but yeah. Well, wonderful talk. And it's remarkable in the amount of research that you've been able to accomplish in midst of being deployed. It reminds me the fact that one of the former surgeons is in chief of this institution. Judith Folkman also spent some time at Bethesda when he was assigned a topic of creating stable blood product replacements presumably for going with the nuclear submarines, but that not surprising for Dr. Folkman, that he had some extra time and actually started some of his initial research on the tumor antigenesis question while he was down there. So I think you're following his model in the stellar fashion. Congratulations. Thank you, sir. Others? So great to have you back in great talk. Thank you. I have one question about kind of the pragmatic application and I have to admit my question is a little colored by seeing a very traumatic movie over the weekend called Warfare. I don't know if anyone's seen that, but it's pretty heavy. And when you kind of conceive to do ECMO for traumatic arrest, I'm sure there's going to be a lot of polytrauma brain injury. The idea kind of approached the anticoagulation issue. One is getting this thing being modular, getting out there in the field. Is there any work or thought about how do you manage that? It's going to be a pretty tricky situation for making the blood just thin enough, but with all these other polytrauma protein with the brain injury. Yeah, it's a great question. It's interesting to me because if you think about it, quite a lot, but these are part of the lethal triad. I guess if you were to, without ever being taught that it was called a lethal triad, and you were observing patients who were dying, who had acidosis, quadcopathy, and hypothermia. You also see examples of patients that live with acidosis. You see patients that live with hypothermia. In fact, we use it therapeutically. You see examples of where actually it's the micro-thrombus and the hyperacoriculability that's almost scarier than the bleeding, maybe not in intraventricular hemorrhage, but more so in the adult trauma population. Then you were to critically think about this triad, and maybe perhaps teleologically that this triad is an evolutionary adaptation. There's something going on physiologically where these mechanisms are occurring. So patients becoming coagulopathic, hypothermic, and acidotic to physiologically tamp down some of the things that would proceed to death. And so over the long run, those are the patients that survive, and those mechanisms continue on, but we, I, atrogenically try to reverse them before the insult is ready to be reversed. Or we reproduce in a strategy that's not conducive. The patient is not ready to be reversed yet. And so specifically to the coagulopathy piece, I wonder if there is a natural benefit to being a little bit slippery, a little bit more prone to bleed. And that might not play out as robustly in our infant CDH population, in the innate old CDH population, but I think it would probably play out more on the adult application. So what has previously been thought to be a big hindrance to go in on ECMO for trauma, I think is actually not as scary, meaning that we will put dramatically injured patients on Hepburn. The head injury certainly I think is very important because it weighs into patient selection. As we select for patients who go on ECMO in the neonatal population, if you have bad IVH, we probably shouldn't put that neonatal on ECMO. I think similarly if you have bad intracranial injury, maybe you shouldn't put that trauma patient on ECMO. But short of that, and with judicious patient selection, we might be able to extend the survival by accepting the use of Hepburn and being a little bit more willing to accept bleeding. The other thing I think that plays into this is some of the strategies like not going up too high on the oxygen too fast and not driving up or altering the calcium too much. I think those things can play a secondary impact on the quadcopathy as well. So all this is a, I think the answer to your question is quite complex. And so as you had asked, the practical application is not there yet. But that's what excites me about the lab is that we can try to drill down on some of these practical aspects and get it like how do you make this feasible because we shouldn't be doing that in human beings. We should start in a model. Well, where at time I think for those who don't realize that the military across all the branches allows very few people to train from general surgery to pediatric surgery. Obviously the demand for medical service is in the military is we're not sending two year olds newborns to war, but our warriors do have children and grandchildren. And so they allow just a few metered out over the decades and we were so thrilled to have the opportunity to have them allow you to come spend time with us and just still collaborate with us in this, I guess, sort of private public collaboration. But I, as you describe, you know, medicine is very silo or a knowledge very silo. It's not surprising that in these laboratory thoughts that people are looking towards cardioplasia to experience with adult cardiac surgery because there's a lot more of that experience. And it probably was an unintended consequence of having pediatric surgeons in the military, of having somebody who's been dealing with the Scheme re-proficient ECMO with a newborn, but the benefit to cross disciplines as unintended is likely going to help those warriors and the rest of critical. So as always, we thank you for your service in there and in here and we always continue to part our family and thank you for sharing with us. Thank you. Thank you very much.