 I'm really excited today to have Dr. Reed and Dr. Kropnik with us to speak to us related to lung transplantation, and I'm sure we'll touch on some of the aspects related to COVID as well. So I'll start off by introducing both of our speakers. I'll start off with Dr. Kropnik. Dr. Kropnik did his undergraduate degree at the University of Michigan, followed by his medical degree at Michigan as well. He did his internship and residency at the University of Pennsylvania, followed by a lung transplant fellowship at Barnes-Jewish Hospital, and a thoracic surgery fellowship at Barnes-Jewish as well. Dr. Kropnik is currently the Vice Chair for Academic Affairs of the Department of Surgery at the University of Maryland, as well as Professor of Surgery at the University of Maryland, as well as a Professor of Microbiology and Immunology. And he is a member of the Greenbaum Comprehensive Cancer Center at the University of Maryland. And you know, this is true for both of our speakers. Their CVs are full of so much scholarship, mentorship, and so much accomplishment. So really looking forward to hearing Dr. Kropnik's presentation. Dr. Reed, Dr. Reed did his undergraduate degree at the University of California at Santa Barbara and his medical degree at the University of Virginia. He did his internship, residency, and chief residency at the University of Illinois, sorry, University of Illinois, Chicago, followed by a pulmonary and critical care fellowship at Johns Hopkins University. He is a Professor of Medicine at the University of Maryland. He is the, I think the Director of Lung Transplantation also at the University of Maryland. So welcome both Dr. Reed and Dr. Kropnik, and I'll pass it on to you. And just a reminder to everyone, feel free to put any questions or comments that you have in the chat and we'll make sure to go through those at the end and a reminder to send all of your evaluations to Barb when we're completed. So welcome. Well, thanks for that introduction. Sasha and I love to hear ourselves talk and it's great to have other people engaged in that. This is my favorite presentation, so we'll begin with that. So we have no disclosures and these are the learning objectives that are CME required for the presentation, but we'll touch on all this. And this is our team and that's my contact and Sasha's contact down there. This slide will appear at the end of the presentation as well, if you miss the opportunity to write down our emails. So in terms of what we'll talk about, we're going to talk about just an overview of Lung Transplant in general, some guidelines for referral. We'll talk about COVID a bit and then we'll have a little bit of a few slides on our own program here. So beginning with the overview, I'll hand it over to Sasha. You can just tell me when to go to the next slide. Yeah, sure. Just a little bit of historical. This is something that I'm kind of a history buff. So the first, the modern era Lung Transplantation actually started with my mentor, Joel Cooper, who'll actually be giving a talk here in January. He's in his mid-80s, but still robust and literally stopped operating a couple of years ago. The first Lung Transplants were done by him and his team in 1983, including a single, which was the first one, then double Lung Transplant. In 1989, the whole team moved to Washington University in St. Louis and a lot of us, myself, Chris Lau, and a lot of us here train with Joel Cooper and St. Louis. Go to the next slide. So actually, if credit is due, the first experimental Lung Transplants were done by pioneering Russians of Russian backgrounds. So Russian experimentalists, but really the first success was by probably the most underrated academic surgeon, James Hardy, who was the chief of a surgeon at the University of Mississippi, he's a pen alum. He did the first human Lung Transplant in 1963, didn't have modern immunosuppression, so the patient got thymic radiation, high dose spread nose on high dose, is a thyroid and died at three weeks, mostly due to lack of adequate immunosuppression. Ironically, the same day, at exactly the same time they were doing the transplant, one of the civil rights leaders was shot. And actually, the resident who was scrubbed in the first human lung transplant, I had to scrub out and go to the emergency room to help with resuscitation. So this was actually overshadowed based. There were a couple more done, but again, without modern immunosuppression, which didn't occur till the late 70s, this was not feasible. Next. If anybody's interested, this is a wonderful book on the history buff by Jim Hardy. And he did a lot of firsts, did the first Xeno transplantation. So he's probably the most underrated academic surgeon out there, but did a lot of firsts. Next. Rob, that's you. So I have a few slides here just on background of transplant. This is conceptually where the anastomosis occur. And a single lung transplant has three anastomoses there. They are bilateral. Obviously, you do the same thing on the other side. The incision that's made is either a lateral thoracotomy or this clamshell incision. And what the clamshell looks like is that it gives pretty good exposure, just some visualization of the surgery itself here. In terms of the transplant itself, it has really kind of boomed and grown every year. And the growth you see is primarily in the purple. That's a bilateral lung transplant, which has really become the favorite transplant largely at most programs for a variety of reasons. The primary reason being that the survival is better. You can see the conditional survival. And the conditional survival here means that if your transplant recipient survives the first year, which is the year that is a bit steeped in risk, the immune suppression and the surgery are at the highest risk around that first 90 days, really. But if your recipient survives that first year, the median survival is 10 years. That's pretty good. Now, this difference between a bilateral and a single is explained in large part by other factors, including the characteristics of the recipient. Older, more frail patients are typically given a single lung because it's a lesser operation, although we've actually had great success in doing bilateral transplants in older population. Sasha did a 72-year-old a couple of weeks ago. And he did both lungs in about 3 and 1 half hours. Typicals eight. So Sasha is fast and able to get a patient through the operating room quickly. That patient is home already and doing great. When we look at the indications for transplant over the years, there was a change in 2005. And that change was the way that allocation occurred began to favor this blue here. And that blue is the idiopathic interstitial mnemonias or IPF. We've gone to calling it IIP rather than IPF because by the time they come to transplant frequently, the diagnosis kind of emerges. If it can be advanced, it represents to be pneumonitis. It can be in-stage interstitial disease from anything. And it gets kind of lumped into this. And that's really become the annual highest transplant diagnosis. But in the history of transplant, COPD is still a major diagnosis. And those are probably the two that we do the most. We're not a cystic center, so this purple band in the middle of cystic is significant as well. Although it'll be interesting in the days of tricapta to see how this pans out in the future. Over time, you can see that outcomes are improving, just through improving the quality of care, improving familiarity, improving just the whole process of delivery of these lung transplants. It's hard to attribute any individual change that's been made in the practice of transplant medicine to this approval over time. And it's kind of a busy slide. You can see that the most modern era in earliest because there just isn't as much follow-up time. So if you look kind of here at three and four years, you can see that there's clearly a march towards better survival. So the old survival data used to be quoted, median survival of five years. And it's better than that now. In terms of survival, according to different indications, here it is. And you can see that cystic fibrosis is young people that typically do very well with the transplant when they get one. This IPAH, that's idiopathic pulmonary arterial hypertension, there is an early mortality. They have a bumpy course immediately around the transplant period. And that can be problematic. But if they get through it, they actually experience a survival similar to cystic fibrosis. And then you have the other conditions that fall kind of into a different pattern. And that's because a lot of the COPD and interstitial patients have more comorbidities. They're older and they have typically smoke. And there's more coronary disease. Age matters. This is an adjusted multigarable regression looking at five-year mortality. And you can see that this inflection upwards at the lower limits is really primarily due to different indications and severity of illness that is taken on and risk that is accepted by programs such as ours for patients in their 20s and 30s that wouldn't be taken in patients that are a little bit older. You can see the inflection point up here when you get up to the mid-60s and older patients do worse. That's not been novel. Now, some programs will look at this and kind of draw a hard line in the sand and say, well, we won't transplant people over 65. We don't draw arbitrary exclusions like that. We will consider patients on an individual basis. And our fundamental question isn't how old you are or whether you have something like that. We ask whether the transplant will do you more good than harm. And that's our primary criteria for selection. And here's a slide where it looks at the outcomes after transplant in terms of what's the expected quality of life. And this is a Karnowski score. It's explained over here. The red are just completely normal people. The yellow is they're imperfect, but they're awfully good. And then you get into this purple. And it's cares for self, but unable to carry out normal activity or active work. And you can see that the majority of people have an awfully good outcome after transplant. And these patients are all disabled and pulmonary cripples when we meet them. Referral guidelines. We'll touch on this a little bit. And I'll give you some of the background on the papers that informed these referral guidelines. These were written initially back in 2006. They were revised in 2014, but largely reiterated. There was a real anchoring bias where they just looked at the prior work and didn't change a whole lot. And if you really dig into a lot of the data informing the initial recommendations back in the first consensus guideline statement, it's pretty small, but it was the best information they had at the time. So to make it as simple as possible, these are really the indications. You really have to have in-stage lung disease. You have to have no other medical options. And as a rule of thumb, if you look at your patient, you say, you know, it's a fair probability that your lung disease is going to take your life within two years, then we ought to be talking about a transplant. And I would even say that if you look at your patient and you think on a five-year timeline, that might be a good time to at least begin the conversation with the transplant team, because an early conversation is very important. Sometimes we get patients that really need some optimization, and it can take a year for them to lose weight and shape, which is hard to do when you don't have the lungs, but we have tricks up our sleeves to make that happen. So the absolute end quotes, I actually cut some of these because in the old guidelines, things like hepatitis C and HIV were absolute contraindications and now they're considered relative contraindications. So I've removed them from this list because those are curable or treatable, at least, for HIV. Malignancy is a problem. The immune suppression that we give with transplants kind of unleashes malignancy. It makes it more aggressive. So it kind of depends on the malignancy. Skin cancers, basal and squamous cell are a problem, but they are not necessarily a deal breaker. Other malignancies that have a high probability of occurrence would portend to a futile endeavor of transplanting them. So it's generally considered a problem. If someone has really bad kyphoscoleosis, and that's for the primary limitation or major limitation to their respiratory mechanics, a transplant doesn't fix that. So those kind of things would be a problem. If the diaphragms, if there's bilateral diaphragm paralysis and the lungs are OK, you obviously don't get any benefit from a transplant. Nonadherence, if you can't take your medicine after transplant, you reject, you die. It doesn't help you to get a transplant. And same thing there, inadequate social support. If a patient is living alone, they can run into problems. They can get confused with their medications. And it's living with someone can be the difference between being found sick and being found dead. So we really require people to have pretty good social support, people that can help them out when they're sick, help them with their medications, get them to their appointments. Substance addiction. There's an arbitrary six month that they need to be tobacco free and they need to not be using any kind of substances as well. So any other major organ system that's untreatable and untreatable advanced, there on occasion we can do a kidney and a lung for an otherwise compelling patient. But if you have a serotic patient with lung disease, we probably are not going to be able to help that patient. If they have heart lung and they're a young patient, then we could do a heart lung transplant. So there are some options for patients with a couple of organs. And we often don't consider it another organ system, but it should be considered another organ system, particularly in the days of COVID. The musculoskeletal systems of somebody is extremely debilitated and doesn't have a lot of rehab capability. Just from being paralyzed and prone for a month, it is a major barrier to success. If they have a non-curable chronic extrapulmonary infection, that's a problem, obviously. Relative contraindications. Age over 65, as mentioned, there are some programs that won't even contemplate a transplant in an amazing 70-year-old. We're not one of those programs. Critical or unstable, if your patient is on ECMO, it's going to take a pretty compelling patient to succeed. Poor rehab potential, as mentioned before. And if you're colonized with problematic organisms, if you've got a multidrug-resistant acinetobacter, it can be a disaster to give you the immune suppression necessary to prevent rejection. Obesity. We do kind of draw a line in the sand there, although if one of the Ravens linebackers came in and their BMI was 36 and their pure muscle, we would probably consider that patient. But for people with a BMI over 35, we typically don't offer them a transplant. We offer them assistance in losing weight in a healthy way down to a threshold where we can expect a successful transplant to occur. Osteoporosis, we can work with that, but it also is a problem. Mechanical ventilation is a relative contraindication as is ECMO and any other medical condition lacking optimization listed there. These are all made worse by transplant. I think that esophageal dysnoitility and esophageal problems wasn't really on the radar of the folks writing the early guidelines. It should probably be on here. It's a major problem. Maybe GERD is capturing that a little bit. Those folks that have swallowing problems and a lot of acid reflux can be transplanted, but they're often committing themselves to being fed by a peg tube rather than by mouth for quite a while. And if they can't commit to that, then they can pretend a problem. Because if they aspirate, they just get recurrent events of aspiration, pneumonitis, and it'll lead to rejection of the lung and a bad outcome. So mostly problematic in your sclerodermal patients. And the gut does definitely function less well after a transplant than it can be a three-month, six-month stent on a feeding tube for some people. It's kind of a classic slide in transplants. There is a risk of being transplanted too early. Obviously, I could be transplanted now, and I degrade in terms of transplant. My long-term longevity would be reduced considerably. We don't want to shorten people's lives. And the risk of transplant itself needs to be factored in versus the risk of the disease. The conceptual slide here kind of shows you the disease course of a patient. Just as an example, you've got the too early to transplant, where you might actually shorten their life. And they've got the too late, where they've hit the point where they're so sick that we can't really help them. And then you've got the sweet spot where you kind of see what's coming. They're still strong. This is your IPF patient that just starts oxygen. If you're prescribing oxygen for somebody with an interstitial disease, they probably need to meet me and Sasha, unless there's a clear reason why a transplant can't happen. Or when you're prescribing OVF or Esprit, it's probably a good time for them to also hear about other options if those options are ones that would make sense for them if they're not 88 and frail. So we'll go through the indications for different transplants. And I'll give you a little background on how those indications were come up with. So COPD, the Pink Puffer blue bloater, classic Netter pictures, our own Steve Sharp here at University of Maryland actually took care of this guy that Netter used as a model for this drawing and says that he looked exactly like that. So don't want to leave out the ladies. The COPD is actually more common in women than men at this point. Thanks, Virginia Slims. So in summary, COPD, these are the guidelines. These are the recommendations. And I'm using the 2006 guidelines. They were changed a little bit in 2014. Some of the changes were a little bit silly. But the core of it was all here. And the recommendation was if you have a code score of five or greater, you ought to go ahead and refer your COPD patient. And then there are recommendations for transplant timing. And I'll include those as well because sometimes if you don't recognize your patient as meeting one is referral criteria, recognizing a transplant criteria, like, oops, I should have already referred. And so there's this recommendation for both score of seven or more. And I'll get into that. And then there's this recommendation that if your patient has ever been hospitalized and manifested hypercapnia with CO2 over 50, that that may be an indication that transplant timing should be sooner rather than later. The presence of pulmonary hypertension and this kind of odd appearing criteria, that may make sense if you recognize it from the NET trial. But if your FD1 is less than 20 and you either have the DLCO less than 20 or homogeneous inphysema, these are your criteria that preclude lung volume reduction. And here's your boat if you forgot what this is. This paper I think is from back in 2004. I think this is kind of what made Bart Shelley kind of a rock star in this publication. He was already reasonably well known. But this really kind of launched him into the extremely famous category if you live in the world of COPD. And here are the points on the boat index. It's dictated by FD1, the distance walk, the NNRC, and a body mass index. And this was way overplayed on the boards for like a decade after this publication that you could get one point for getting skinny. Wow. So MMRC, I'm probably more familiar with it at this point than I am with the New York Heart Association because I use it more. But if you're more familiar with New York Heart Association classes, these are kind of rough equivalents. But that's the MMRC scale. MMRC has also been adopted into the CAT scoring or the gold scoring for COPD. So it should look a little bit familiar. And here was the idea behind the recommendation that you should refer at a boat threshold of five is that that would put you into the quartile three or four. And here's the predicted survival based on the observed Kaplan-Meier from Bart Shelley's original publication. And there's the quartile four that's at a threshold of seven or more that's been used as a reason to transplant. And it was as simple as saying, look, in 36 months, 50% chance of survival, that's worse than the expected outcome for transplant back then. There are a few problems with any of these. And any time you look at a Kaplan-Meier and you use it to extrapolate to a population of lung transplant candidates, it's problematic. And there are issues of generalizability. Patients that are considered candidates for lung transplant can't have cancer. They can't have really bad coronary disease. They can't have active smoking. They have fewer comorbidities than the general population. This population here that Bart Shelley was presenting in this Kaplan-Meier, they weren't non-smokers. They didn't have, they hadn't passed through that lens of filtration to get to transplant. And so one of the things that we posited was maybe our transplant candidates actually have a far better survival than would be predicted by the boat score. And it actually is exactly the case. The red line is the survival of patients that are weight listed for transplant with COPD. And then the green is that original validation cohort from Bart Shelley's paper. And this is, we did a competing in-points analysis, the transplant is obviously a competing in-point to debt. So we did a fine and gray analysis to show that this isn't confounded by a transplant as a competing in-point. And we showed that there was about a six-fold better survival in those patients that are listed for or considered candidates for transplant than the boat score would predict, which makes the boat score maybe not the best thing to use to prognosticate. And got to publish with Bart in chess. That was kind of a fun paper to write. So the recommendation about hypercatonic respiratory failure in COPD comes from this publication. And this was about 1,000 patients with COPD. This was back in the late 90s, back before home non-invasive ventilation was as easy to come by. And this was that threshold of 50 mentioned in the guidelines. And it was mostly chronic hypercarbia, but the mortality was pretty significant. At one year it was almost half of the patients that presented this whale were dead. And again, there's some issues with generalizability, but it does indicate that you have patients with very limited pulmonary reserve. And that might be a good reason to go with transplant. Pulmonary hypertension has long been known to be a prognostic importance in COPD. And here's one of the early pre-oxygen observations. And it holds true even after long-term oxygen therapy has been implemented that patients with pulmonary hypertension and COPD do worse. And so that's one of the indications to consider a long transplant as well. This was from the NET study and the surgical arm versus the medical arm in this subgroup with the very low FVV1 and the homogeneous emphysema or the very low DLCO, the surgical arm did worse. And this was the information, the informed inclusion of that criteria in those guidelines. So these all come really from those three studies and so the data are a little bit soft. There's a little bit more art that needs to be incorporated into the science, but these are the guidelines. And I think that just recognizing that you have a patient that's sick is probably the best way to make your referral. So here's your IPF or idiopathic interstitial pneumonia, fibrotic NSIP and IPF cluster together in terms of your referral. And the recommendations on when to refer is really when you diagnose. If you have a diagnosis of UIP or fibrotic NSIP, the day you diagnose it is the day you refer them for a consultation for transplant, unless there's an obvious reason why a transplant is not an option for them. And then the timing for transplant is more complex. For UIP, there's this DLCO threshold of 40, 10% FVC decline. If your DLCO is trending down, pretty much anything that's trending down that says my patient is getting worse if their oxygen requirement is new or progressing, any of those are triggers that you ought to move forward. Hypoxemia even during a six minute walk test is an indication that your patient should be transplanted sooner rather than later. Honeycombing, so we can just look at the CT and if it is an extensive degree of damage that is considered an indication to go ahead with a transplant as well. For fibrotic NSIP, this DLCO threshold is a little bit lower and that 10% decline in the biocompacity over six months holds true. These recommendations come from Kaplan-Meyer's of relatively small observational studies and here they are. You know, this was actually a larger observational study just trying to get a sense of how long patients with IPF live, it was 900 patients and the median survival here was almost four years. The problem is this was an overestimate of survival because it was cross-sectional in its enrollment. It wasn't just incident, it was incident and prevalent cases, so prevalent cases are those who are gonna survive longer and the longer you survive, the more likely you are to be captured in this. So excuse towards a better survival. But it creates a good bookend to say that that of the patients that you've got right now, this is kind of the better predicted survival that you can expect and this is really true for IPF. You really do have kind of a plateau and then these drops and if you have somebody with IPF that has one of these drops that has an IPF flare, you treat it, you get them back into their home but they have maybe a little bit more oxygen requirement. That's really telling you that you can stabilize them and it's time to consider moving forward with a transplant. And here what I was mentioning, the Kaplan-Meyers showing that these declines in vital capacity, there's a couple of papers here that have shown that decline of 10% kind of matters. I would argue that this decline of zero to 10% is something to certainly keep an eye on. And I think that it certainly justifies doing frequent pulmonary function tests in these patients because you can pick up on these changes and oftentimes the DLCO changes even before the vital capacity does and it can really tell you what's coming and when to expect your patient to kind of hit the wall. The, and these studies were pretty small as well but what you can see is that in the patients with NSIP and IPF, the change of 10% matter here in these studies as well, this was 179 patients. And then this was the DLCO data that informed that recommendation of 35% for NSIP because you can see that the Kaplan-Meyers is poor but these recommendations came from experience of 12 and 16. It's not super robust. And I mean, your anecdotal experience at least mine because I do this work with UIP and NSIP already exceeds what the published data right here are. But I think that just recognizing that that DLCO as well as the DLCO trajectory can be very informative about when is the right time to move towards transplant with the patient. I poxied during a six minute walk test there were these observations that if the SAT was less than 88 it was considerably worse. Sick patients do worse is kind of a theme in publications. There are quite a few of those out there. This was kind of interesting though the distant saturation product. There are some issues with this around transplant but because our ideal transplant patient would actually be somebody who can walk a really long distance but their oxygen is awful. And we have a lot of those patients because we work very hard to keep our patients robust, healthy, physically fit other than their lungs. And we spend a lot of time improving this distant saturation product but this is a six minute walk test where you take the distance walking meters and multiply by the lowest oxygen saturation on room air. And if that number is less than 200 they fall into this category rather than that category. So there's your summary and you can take it with a grain of salt as you want. I think that the important thing is the referral timing earlier is better so that there's room to optimize these patients for transplant as well as to be able to be cognizant of how we can optimize them for a transplant. The transplant evaluation is kind of an extensive battery of tests and it's challenging to do it quickly. We would have to admit a patient to the hospital to get through it in a week. It frequently takes several months to get through as an outpatient. So it's best to start that process early. All right, so this is the next condition. And if you can see the lumpy bumpies through here you can probably guess that this is sarcoid. So sarcoid, the recommendations for referral are New York Heart Association three or four despite optimal therapy. The threshold to transplant them are hypoxemia. So if you get a sarcoid patient who is hypoxemic it's a reason to refer as well. Pulmonary hypertension, another reason to refer that right atrial pressure over 15 indicates that your right heart is beginning to fail. Your next indication here, if you know what this is, is a big pulmonary artery with that's become really problematic all the blood, these little blood cells are trying to get through that thing and they're doing their best. This is idiopathic pulmonary arterial hypertension. And it's kind of similar to sarcoid referral guidelines that you have to have optimal therapy, obviously. If you're failing Rivadio and you tried nothing else then sure, send the patient to us but we'll tell you that you gotta fail flow in or equivalent to really be sure that you're helping the patient with a transplant. Rapid progression is obviously a good reason as well to get that patient into the realm of transplant. So when the transplant is either that, you can kind of remember this easier by thinking if you can walk 360 meters you can live 360 days but if you're less than that then you ought to go ahead and get a transplant. If, so either you have poor reserve or you have a trajectory you don't like that's the rule of thumb that I think is probably the most useful. They have to be failing something like flow in or equivalent. They have to be failing the optimal therapy. Low cardiac index, high right trail pressure those can be reasons to transplant as well. Moving on to COVID, I'll talk briefly here. This is supposed to be a little animated graphic where it starts popping up COVID but I don't think the animation is working so I'll skip it. I'll just cover a couple of cases that reflect our experience here at Maryland and hopefully we'll have a couple of moments for comments. If there are comments in the box I'm not seeing them you can feel free to unmute yourself and stop me. This was a young man, 24 year old from Georgia from before vaccines were widely available and he got COVID in April and was cannulated. This was mid-April and he was cannulated for ECMA as one's just failed rapidly as we see repeatedly play out during the pandemic. He was cannulated about two weeks after he was admitted to the hospital and he developed pneumothoracies and VRE bacteremia, pseudomonas pneumonia. The wheels fell off the bus, he was paralyzed, prone and super deep condition. He had bradycardic arrests. This is something that we've seen repeatedly is these bradycardic events that seem to be something directed cardiac in addition to the propofol and the precedents that people are maintained on. He had pacing wires placed for that and he was transferred to us on ECMA in mid June, quite deep condition. This is him, I'm including pictures of him because he's kind of come out as a big vaccine advocate and has made his story public. There are a bunch of news stories about him. This was him having a good time in Florida. He was actually very cautious around the pandemic but then went to one concert and took his mask off and the rest is history. Here he is on vapor therm for that two week window before he crashed and this is how we got him. He's got your ECMO cannulas and he's a little bit of deminus and he's weak but he's awake and he can talk to you and we could have a conversation with him. And this was his CT scan. You can see the usual chest tubes in place and he's got this characteristic pattern. These patients often have an upper lobe and an interior predilection to develop these little blebs that will pop and lead to pneumothoracies and bronchoporl fistulas and there's his pacing wire right there and his ECMO cannulas went too fast. So that's his lung when it came out. Try as we could, his lungs were just shot. They cleaned this up considerably when it was on the back bench after removal it just looked like a little red piece of liver. There wasn't much to it. He got his transplant and even though he was markedly deconditioned we were willing to take a risk on his degree of deconditioning because he was 24, 24 year olds are damn hard to kill. This was supposed to be animated. Let's see if the animation works. This is him learning how to walk again after not having walked for several months. We have a pretty robust support at Kernan, the University of Maryland Rehab Orthopaedic Institute which is where this was shot is very good at getting people back on their feet. And there he is recuperating after his transplant. Happy as a clam. So let's see, I had another slide on him but I don't. So case two, here's a man with who's 50. So this is a little bit older gentlemen than our last and he got COVID in January of 2021. And he was intubated about 10 days later. He ran that course of getting really sick, really fast. And he developed these pneumothoracies on both sides with just an enormous air leak. We were consulted around this time because they couldn't ventilate him at all. His oxygenation wasn't terrible but he had these huge blowing air leaks and they consulted us for ECMO and they consulted us for transplant because they were concerned that there was no other option and he was really unstable. By the time we were consulted, he was also, he was so sedated, he couldn't talk to us and he was not like the last one. We couldn't even have a conversation with him and talk to him about his preferences for transplant. He was extremely deconditioned, couldn't lift his bed, his arms off the bed when we'd lighten sedation. And here was his scan. If anything, it looks maybe worse than the last case. And you can see that again, we've got this upper lobe with an anterior kind of predilection for this stuff and you've got some lower lobe, traction bronchiectasis beginning here. These pneumothoracies that sit up here are challenged. Couldn't be ventilated. There were some problems in moving forward with him. He wasn't yet six weeks out from his first COVID test. This was in the early days of the pandemic, we had to work in a multidisciplinary fashion with our transplant ID folks to come up with an algorithm of how to move forward with patients with COVID so that we didn't just transplant them and have them die of a virus that was still in their system. And this was the algorithm that we came up with here. So this gentleman, to review the timeline with him, he had COVID in mid-January. He actually never required a transplant. We just pruned him. Those upper lobe anterior blebs will frequently respond to pruning. We put in some endobronchial valves as well. They were partially helpful, but the pruning really allowed those bronchoploreal fistulas to heal. Discharge him to home two months later and he never got a transplant. So we consider this a success. We don't just transplant, we're not a barber. You don't send somebody to us and we give every patient a haircut. We will do our very best to try to salvage a patient without a transplant when possible. CT on this patient was repeated in June. And this is interesting because this was his CT that I showed you before. And you can see there were some of this traction at the bases. It's not normal, but most of these abnormalities that we would have fought would be fibrosis and scarring or not. They actually recover and the lungs look much better than you would expect them to. Here's another slice even farther down where there was this little patch that looked like traction and irreversible damage and a paired slice from his later CT. A lot of this may be survected dysfunction leading to the collapse of the LVLI and traction that does not reflect fibrosis. So how do we predict who's gonna live and who's gonna die, who needs a transplant and who can be bridged through? There's an arc to it and a lot of it is anecdotal experience right now and a lot of publications are local we did kind of publications. There is this preset score idea that pertains to ECMO and that you calculate like this, they're online calculators for the preset score. This was adopted a little bit by our ECMO folks here at Maryland and, you know, Alita Bhattabhai and 16 of his closest friends published this experience pertaining to the first 40 ECMO COVID cases. And what they say is that the outcomes have really improved since then largely because of selection. They didn't really know who was the ideal candidate to bridge to recovery at this point and they've become a little bit more selective. So it does make it harder to get patients in but if you get your patient in and on ECMO what their more updated data would suggest is that 70 to 80% of those people will ultimately go home. 33 of these 40 at the time of analysis had had ECMO discontinued and 18 of those were survivors. This is 18 of the 33. So these other seven, we don't know what happened with on this publication but there were about half survivors and again, this was the early experience and they're doing better now. There were 15 deaths and it seemed like that preset score was indicative of who was gonna survive and who's gonna die. There were other things that were indicators of death. That the development of those new authorities was a negative prognostic indicator. Failure to observe improvements in the compliance was another indicator of the mortality. Another example of the city you are, the more likely you are to die. So I'll hand it over to Sasha here to talk about our amazing program. Thanks a lot. Yeah, so our program's gone through a lot of changes and Rob and I are both new. We've been, Rob's been here but he's the new medical director of the Lundcrest Bourbon. One of the things that's changed and one of the reasons I was recruited by Chris Lau who's right there in the center. She's actually a chair of surgery and she's a lung transplant surgeon as well. We trained together and Joe Cooper had watched you a couple of years apart and we really wanted to grow a program and truly make it a program. So you see there's a couple of people on there that whose pictures we don't have. There's also two more MPs we are looking for. So part of the reason is we think that lung transplantation access is difficult in Baltimore. In fact, looking at similar cities with similar populations, the numbers and accessibility to lung transplant should be two or three-fold. So I think there's a lot of people that we could help that aren't being helped and are probably dying not knowing that this resource is available. So that's what we wanna let you know. We're wrapping up a team. We have a commitment from the institution. They wanna grow the program and we're happy to see anybody anytime and evaluate. Obviously nationally about 10 to 20% of people referred for lung transplantation actually turn out to be lung transplant candidates but we're happy to see anybody and we'll call you and give you an honest opinion. If somebody's not a candidate, here are the reasons. This is why age, comorbidity, coronary disease, malignancy and there's our referral line and we have coordinators available essential at time if you wanna go to the next slide Rob. One of the things that we're focused on here is not just the clinical care. We're also focusing on basic understanding and basic research as well as clinical research. And one of the things that we brought here is a lab that studies essentially what should be lung specific immunosuppression. And part of the reason as Rob showed you is that long-term survival of lung transplantation is probably the poorest among all organs. The only organ that really mirrors it a small bowel and in both these mucosal organs that are constantly exposed to the environment. So we have some hypotheses that simply decreasing non-specifically the immune system is actually damaging to the lung. Go to the next slide. We actually developed a model. Niki Okazaka was one of my fellows who when we were at Washington University develop a mouse model and we do a lot of modeling and the mice actually really mimic the human situation. Next slide Rob. And we have multiple lines investigation funded by the NIH as well as private institutions, individuals as well as foundations that focus on unique immunological aspects of the lung that make it different than hard lung kidney. And we're starting to develop immunosuppression strategies that will be working. And I wanna call a more tolerant strategy rather than immunosuppression strategies that will be long specific. They may apply to the gut but might not necessarily apply to kidney or some of these other organs. Next slide. We also have several investigator initiated trials. Chris Lauer has an R01 for a clinical trial where we're studying a drug adenosine which is essentially agonist of adenosine receptor agadenosine which is a drug that's actually used for imaging but given in higher doses we've shown that it can reduce ischemia or perfusion injury. We have an active trial going on right now. Next slide. And we have a very good partnership with lung bioengineering. A lot of the lungs that are considered marginal for transplantation, our team will go out, will harvest and we will put an ex vivo lung perfusion which both dries the lungs out and essentially evaluates them whether they're suitable for transplantation. We usually do about a dozen to half a dozen a year. These are organs that are considered a little bit high risk but we bring them back. We perfuse them, we assess them and a large number of them will be able to put into patients to benefit our patient population. Next slide. And again, this is our team, some of our team team is much larger but these are the only people that can make it to the picture. So that's really all I have. We have any questions? Thanks very much for such a wonderful presentation. We have a, oh okay, that's your message in the chat. So please the chat is open for anybody that has any questions for our presenters. I guess I'll get started off. Thank you again. I really liked the melting from the medical and the surgical side is hearing both sides and the hearing the COVID experience as well. Wondering both sort of anecdotally and what the data is about socioeconomics and lung transplantation meaning, what are the barriers in terms of geography where you live in the country and socioeconomics and who seeks liver transplant? Yeah, thanks for, that's a great question and I appreciate it a lot. Our program actually, that's one of the great strengths of our program. When we compare our program statistics against the programs across the country, we serve a far greater proportion of minorities. We will take on patients that don't speak English. That is a barrier and it makes it a challenge but it's one that we have developed some ways to work around and we've got quite a number primarily Spanish speaking only patients that we're able to take on and help out. And that's definitely something that I've seen other programs struggle with and not be as enthusiastic about taking on. The socioeconomic barriers are real. If you can't afford your medications after transplant, it's a disaster. It's kind of odd, Medicaid, we have a number of Medicaid patients and they can actually afford it. Medicaid is actually not a bad insurance. The times where we struggle and we had this happen a couple of weeks ago where someone only had Medicare and they didn't have a supplemental and that only pays 80% and then it leaves a 20% gap and we don't have a workaround for that. We ended up rather than just saying, sorry, you have to die. We worked really hard to find that patient a way to get a supplemental insurance. The only one they were able to get was Kaiser and Kaiser doesn't work with us. They work it with UVA because when Sasha was at UVA, he worked with the institution there to bring in a Kaiser affiliation. And so now... We're working on switching that to us. It's just a little bit more bureaucratic. We'll take a little bit, but soon. We'll get it, but we sent that patient down to UVA to be transplanted. And I think that was another success for us because we don't stop it. We can't help you. If we can't help you, we'll find a way to help you. It was sort of the approach that we take. And that was a long-winded answer that allowed me to move past the question. Did I answer your question there? Absolutely, because it feels like lung transplantation in particular, I feel like it's sort of different than liver that there seems to not be early referral, early assessment and early evaluation. And so along that line, is it similar to liver in terms of regionality of organs and all of that? How does that work in terms of lung transplantation? Yeah, it actually, it's kind of, so one of the things that's happened and one of the reasons actually, I move here is the allocation rules change in 2017 based on a lawsuit in New York. So before, and liver I think is going the same way or maybe it's already gone. Before you had your United Network of Organ Sharing is divided into 50 regions, kind of loosely mirror states, but not exactly. And it used to be that no organ could escape your region without exhausting all the recipients. And it became a very apparent, there was a very unfair system, especially in Manhattan, people were dying and right across Hudson River, people with much lower acuity were getting transplanted because it was a different OPO. And there was a lawsuit, so now it's a 250 mile rule. So when we list the patient, a line is drawn 250 miles around our patient, our institution and the person with the sickest score gets the first crack at the lungs. And that's one of the things Rob didn't point out. If you look at our program, compared to all the other programs, our lung allocation score, the degree of sickness is statistically higher. We are much more aggressive, we are not conservative and we believe, look, there's patients that have four, five, six months to live, we'll give them a shot if there's no absolute contradiction. So that's one of the reasons we've been able to benefit is by having sicker patients about a third to maybe 40% of our transplants is off of ECMO. They are so sick that they have to have ECMO beforehand. So we've been doing well with getting the lungs with this new 250 mile rule, which has benefited our program and has benefited the sickest patients. Overall in the country, that has driven perioperative mortality higher because the way to get success is to transplant a patient who's at home not sick. That's how you're gonna get great outcomes, but then the sickest patients are gonna die. So it's a fine balance that's going into play. But our strategy is we're gonna go after the sickest patients and that's where our institution fits in. And we feel that it's our mission to serve everybody in Maryland, the state sponsors us for that reason and to try to take care of the sickest patients that have no other choice. But we would love earlier referrals. We'd love nothing more than to evaluate the ILD patient early because the worst thing is they have an ILD crisis. They end up on ECMO and we have to work them up in-house. It's very emotionally hard, rather than work them up early. We don't list them, but we have all the dots checked that if they do have a crisis or they rapidly deteriorate, essentially all the boxes are checked, we can list them pretty quickly. Thanks very much. And last question, just the role of the transplantation in our current era of COVID, what have you seen in the, like, I guess, now that we're approaching a year that the vaccine has been available? Are the numbers stable? Have they increased or decreased over this past year? Oh God, we get a call. We get, we probably get a call every other day. My patient who didn't want the vaccine regrets it. Can he have a transplant? And so far we have not been able to help many of those people. It's rare, we have had a couple of patients, and I got a call last week where there was someone who was a vaccine refuser who was sick and the family, it's still vaccine refusing. And I said, there are a number of reasons why we couldn't help that patient. They were medical, the kidneys were failing and the platelets were bad. But I was like, you know, transplant a patient and just put them right back into the lion's den and have them get COVID again. It takes a toll on us to contemplate that. So there's a lot of very challenging issues to navigate. We have the stance that we've taken with the vaccine refusers and virtually all of the patients with COVID that are being referred to us in the last month or two have been vaccine refusers, nobody else. And the stance that we've kind of taken with that is that it's like smoking, bad mistake, it's stupid. If you quit and you change your ways, we're not gonna hold it against you. If you recognize that it was a mistake, we'll do our very best to help you out. If you stick to your guns and you double down, and you say, we're not gonna work with you medically, we're not gonna take your medical advice, we're not gonna listen to you on this. We put that sort of in the category of medical non-adherence and we can't really work with you. I'm hoping that as this pandemic moves on into the endemic state, that this won't be a continued problem. I think that virtually everyone out there is either gonna get the disease or get the vaccine and so we're gonna continue to have some cases here and there, but hopefully it'll become much more of a sporadic thing like ARDS after flu is. All right, well, thank you very much to Dr. Reed and Dr. Krupp for a really wonderful presentation. Thanks for spending this past hour with us. Thank you. All right, take care. Thanks everyone for joining us. Thank you. Bye-bye. Have a great rest of your day. Bye-bye. Thank you.