As he struggles to find his unmute button. Um, thank you, um, everyone. So great discussion, really appreciated your talk, Tracy, um, very important stuff. Um, I'm gonna switch gears a little bit and we're gonna go to long-term data. And before doing that, let's see, I think, um, I have some disclosures, uh, to report, um. Uh, in terms of consulting for both of our sponsors. Thank you again very much. Um, and, uh, I won't be really discussing any commercial products during this talk. But what I am gonna say ahead of the, the, the slide deck really is, um, I think as pediatric surgeons, we learned a long time ago, uh, when our, in our training and, and throughout all of our careers, what we do for patients in a very critical period of their lives, whether they're neonates, uh, prematures, For older kids or teenagers, as we have an opportunity to intervene and do a really good care, uh, including surgical operations that have a lifetime consequence. And I take that as a, a humble as well as uh incredibly important responsibility, um, because if we get it right, then they can do extremely well regardless of the operation. Um, but there are a lot of ways that we, we do this. It's a complex equation, both surgically and psychologically and all of the interventions around the dietary piece. So I just wanted to remind everyone really that when we're taking care of patients in an adolescent, uh, bariatric center, um, we, I think that we have a precious opportunity and it's a limited opportunity just based on how the, the patients do follow up with us for a limited period of time. Um, I think it's a, a precious opportunity to, to get it right, and I just wanted to remind everyone that that is, you know, what we're all about. The 6 months ahead of time, as well as the few years, uh, postoperatively that they, they're coming back to see us, um, is really important. So what you see here in the first slide. Um, is, uh, some data that was pulled and not published but pulled from, uh, the Children's Hospital Association's, uh, database called FIS, um, and it does show this kinetics, that was one of the questions, uh, kinetics of, uh, of use of surgery in, uh, the CHA system, uh, from 2010 to 2022. And the bottom line is it's growing. Uh, the numbers are probably different than Mark showed from the NBSAQIP database, uh, but sleeve gastrectomy in the green has really taken over and very few bypasses are being done in 2022, uh, and last year, and, um, and very few other operations as well. Early on when we first proposed um a longitudinal study to look at bariatric surgery, we had to sell it to NIH with a, with a punchline. And what we did is we proposed that early intervention for um ser serious weight uh problems in youth um would be a better outcome, surgical, uh, would be a better outcome in youth than waiting until adulthood. And that, uh, that team lab study that's been mentioned, uh, is, uh, was multi-institutional, uh, about 242 subjects, and we did longitudinal assessment preoperatively and then at time points postoperatively. Um, we're proud to say we're in our 17th year of, uh, funding now and things will be coming to a close, um, before long, um, but I think we've squeezed, uh, a lot of good data out of it with our centers that are shown across the top there. Um, so, it's just a, a usual diagram of, of, uh, the recruitment and I'm gonna save any details here, but just to say we had 242 that underwent surgery, 219 still active, um, and, um, and, and the, the retention then is, is really about 85%. Um, the outcomes after gastric bypass, um, are what we're talking about today, and I was gonna point out that the adult lab study was our comparison group for teen labs. Um, and these were gastric bypasses only. We recruited in teen labs. About 160 some bypasses, um, and then another 100, uh, sleeves. The, um, uh, the bypass comparison though to adults shows that the weight loss, whether you're a teenager or an adult and have the same operation is the same, and that's shown here. You have about 26, 29% weight loss at 5 years. But the really interesting thing is, um, as we predicted, as we sold NIH uh on the study, uh, we were able to make good on that and find that there was a difference in long-term effectiveness of the operation, um, in favor of the youth. So, Um, as you see in the left panel, 86% of the teenagers turned around their diabetes, um, whereas only 50 53% of the adults did at 5 years. Similar story for hypertension, um, with, uh, the, the teenagers, um, uh, having 41% remission rate, um. Sorry, 68% remission rate at 5 years and the adults are only enjoying that remission at 41%. So, um, uh, this talk again, long-term outcomes, it's not all about teen labs, even though it's been a great part of my, uh, my entire career. Um, what, uh, Andy Beamish did, uh, from, uh, from Wales, uh, England was to pull together some of the other studies that have been published, including one that he was involved with, uh, called Amos, um, which was a Swedish study. As well as FBS Five, which was a single-center study that we, we, uh, we did in Cincinnati before Gen labs. And then Ayed Al-Kahtani's work from Saudi Arabia, and then, um, uh, Nestor uh uh Dela Cruz Munoz work uh from Miami. And what you see is great weight loss, uh, regardless of the series and the procedure, uh, complement. Um, but the point here I'm gonna make, uh, these are all long-term follow-up, either 57, or even 14 years from, uh, Nestor's work, uh, shows that there is a, um, uh, a dominant signal here that hypertension is very, um, significantly impacted, uh, reduced or remission rates shown here, uh, 68%, 58% to 100%. Um, type 2 diabetes, uh, remission rates at 86, uh, 72, 100%, dyslipidemia reversing. Um, even renal dysfunction reversing, and we, we looked at that through either measures of hyperfiltration or, uh, target organ damage, uh, in the form of, uh, of urine, uh, urinary albumin levels. Uh, liver dysfunction, uh, very few studies have actually focused on the liver, uh, but we can see the numbers, the transaminases, uh, remit, um, uh, in very high percentages and even biopsies that we've done as well. Long-term and teen labs, um, we, uh, are gonna show you the good, the bad, the ugly here, and this is a percent BMI change at uh 1 year, nadir, um, at about 33%. And then over time, a very gentle increase so that at 10 years, we're still tracking at 21% average. But look at the, the, the heterogeneity here. This is an incredible amount of heterogeneity and to help uh dive into that and understand it better, our statisticians are very good at, um at this uh. Um, uh, latent class modeling, um, uh, procedures with, uh, SASS, and what we're able to discern is that they're at 10 years are a few different, uh, groups, some that have gained weight, 11% or so, and some, uh, that have, uh, have about a 44%, uh, weight loss, and those are about 20% and a few in between. You know, the holy grail for bariatric surgery has always been how do you predict early on or preoperatively, how do you predict which of these groups you're gonna end up in? And I'd, I'd like to say that we have the answer but we're still working hard on that one. Um, I'm gonna, uh, pivot to, uh, you know, as, as I, as I mentioned, um, uh, we're gonna talk a little bit about the good and a little bit about the concerning part. And this has already been mentioned earlier today, um, but Gretchen White, uh, has really helped us dig into our audit data in teen labs and, uh, showed that, uh, in essence, as we might expect as people are developing, these teenagers developing and, and emerging into adulthood. Um, 8 years out, we see that there are, uh, really a minority that haven't had, um, experience with alcohol. And we have a number here that, uh, um, uh, the most of them have had some experience with alcohol. The cumulative incidence of alcohol-related problems by time in both the sleeves and the bypasses are shown here. And that is, um, that it really does approach uh half of them uh by Um, uh, by 8.5 years. And so what we, um, what we are, are concerned about, of course, is, you know, uh, are they behaving safely? Uh, are they experiencing these risks in a different, at a different rate or at a different, um, amount, uh, than their peers, um, that never underwent surgery. And of course, we, we know pharmacologically, uh, the, the PK um and, and uh what was it PKPD, um, you know, the pharmacokinetics of alcohol are much faster hitting the system after gastric bypass and probably sleeve gastrectomy as well and so this kind of, um, anticipatory guidance that we have to provide our patients related to drugs. Of all types, but particularly the most common, uh, one of the most common drugs, alcohol, uh, certainly is, uh, highlighted by these data. Tom, just quick question, I'll get the discussion going. I know you're not done yet, um, but what, what are the, what's the normative data on the alcohol use? So what, what, what, what's the average risk of the kid who's not having surgery? Yeah, that's a great question and, and, and what is that kid is the, is the answering a question with a question because we didn't have a um a severely obese uh group that was like, you know, identically matched and had all of our measures. Um, we're at a little bit of a loss to know what would have happened to the group that is the appropriate control. Normative controls. Actually adopt alcohol use, um, uh, earlier and to a higher frequency than our patients do when we've done the comparison to previously published data. Um, so I think that when it comes to alcohol at least, we have some normative data that would suggest that these patients are not adopting it at uh as higher frequency as, um, normal weight controls. Or maybe Tom, I'm sorry, or maybe they're just delaying. Right, so again, we were talking a little bit before how their developmental, like where they are developmentally because they've been isolated a lot of times, maybe just stunted, and so they may just be adopting a little bit later than their peers. Yeah, you're absolutely right. And actually when we answered this question to a data safety monitoring board over and over and over again, we would, we would always go back to this Edmondson article and um it was a point in time, like a cross-sectional study, and you have a fair point. Um, that over time, uh, these kids probably do catch up as they become young adults. Um, in the interest of time, I'm gonna get to this one now, which is a sobering slide, and so I didn't go over this part, the part in the very middle, the 14 deaths, um, because I wanted to, to, to, to place it here after, uh, the alcohol talk, and that is, um, that a lot of these patients that died over the years, and first of all, um, the, the first death was at 3.3 years. So these are, are not evidence of a lot of perioperative complications if you will, um. That were, were uh mortal complications. These are, uh, 3 years out, you know, as you see, 7 years out, 10 years out, 14 years out. I'm really proud of our team, our research team that collected this data very rigorously and you can only have this kind of data if you have, you know, a very high proportion of your cohort that's still, you know, coming in for the regular visits or in touch with the coordinators. So, a punchline here though that's not seen in the study and the thing that's got us Concerned as well as the uh as, as the, um, you know, uh, the, the research side of us as well as the, the doctor side of us is that there is uh there are a number of these that did have multi-substance uh use um associated with the death and this is not published yet but it is something that we're following up on um by doing some more detailed digging on, you know, what are the circumstances, uh, surrounding the deaths and I think this is a story that has to be Told. It's very rarely told and we plan to tell it in, in as uh uh as robust a fashion and detailed a fashion as we can, um, because that's our responsibility, you know, to again talk about the benefits of surgery, talk about the things that happen, whether they're related to surgery or not, and again, many, many years after surgery, I think there are, um, multiple factors that go into the experience of our patients, um, uh, which is something that of course just makes common sense. So, um, I'm gonna wrap up, and I don't know where I am with the clock, but the hook didn't come out yet. So, uh, long-term literature does, we were close, we were close. Long-term literature supports, uh, effectiveness of what we're doing here, um, and that is, uh, that comes through, uh, very clearly from teen labs and other studies. Uh, but there is a wide spectrum of weight loss outcomes, um, and, uh, and you saw it. You saw the robust heterogeneity in those outcomes just like any other intervention for obesity. Uh, we see it with bariatric surgery and it's a land, uh, it's a, it's a gold mine of an area for research. Um, major improvements that we're seeing, uh, in, uh, the complications of obesity are very gratifying and it's really the reason I get up in the morning because I like to be able to go to the operating room and cure, uh, cure obesity as well as type 2 diabetes. Um, but we do need to give anticipatory guidance around, you know, potentially adverse effects of surgery when it comes to sleeve. We worry about reflux. Um, we worry about, you know, doing the best possible operation we can. We talk about the anatomy-based, uh, sleeve as a way to prevent reflux because we, we don't want to leave a pouch up at the top. We don't want to have a dump. Dumbbell-shaped stomach. And I think what happens in the operating room, the magic that's there with the capable hands of, of the surgeons is critically important for the long term. Micronutrient deficiencies, they got to take the vitamins, uh, not like supplements, but like medicines, and that's what we, we, uh, we hit that hard preoperatively and postoperatively. And then the whole, you know, real critical importance of the mental health professionals and helping us to make sure that patients understand that their behaviors are the, uh, are, are, are the key for being successful or having less than successful outcomes. And then, as also has been mentioned, rescue therapies for inadequate weight loss and weight regain, really important, whether it's the, the 2nd gens or whether it's the 3rd gens or whether it's the 4th gens to come, uh, we got a partner with our, uh, our, our, our AOM uh expert partners, uh, on the medical side. We have to learn how to prescribe ourselves if we don't have such a partner. Um, and, uh, and this is, uh, I think great things to come, um, but based on the, the long-term data we have so far, I think that we're doing, uh, we, we really have some optimism. OK, so we got 3 or 4 minutes for questions, Tom. All right. So, anybody have questions for Doctor Inge? I don't know if this is a question, but I'm just struck by the 14. Right, I mean that really, um, again, I feel like We know that the patients that we care for that come to us are, um, that they do have, that they're disenfranchised in many ways and that, um, And that a lot of that doesn't necessarily go away just because we've improved their weight status. Let me, let me react to that real quick, Karen, um, and because Meg Zeller in Cincinnati did recruit about 81 teenagers severely obese, not as obese as these, but followed them out and We are, um, we are doing, uh, a good job, I think, of working with her to try to understand what is the mortality, early, 10-year mortality of that group too. The initial back of the envelope gives us a little bit of, of, of peace of mind, not that we, you know, don't, our hearts don't go out to these families, of course, after losing a loved one, but a little. a peace of mind that it might not be a signal around surgery, but it's a signal around the disease of severe obesity in teenage years that leads to earlier death, and we've certainly seen that in the Fontaine data, uh, you know, JAMA earlier in the 2000s when they looked at the, the years of life lost due to being severely obese as a teenager. So, I think we're gonna see that play out in our patient population. I think the rescue that we're trying to give them for better quality of life for those years that they have can't be underestimated though. Uh, it's, it's very sobering and, you know, I was gonna ask, I was gonna ask, you know, a similar question that you answered just now, Tom, you know, again, what's the normative data? And, you know, we, we might actually be doing better for these kids, but don't know that. And again, you know, I guess for Tracy, uh, you know, I, I think we need to figure out how we can intervene and what, what is it that's You know, what's the underlying cause, probably related to the underlying cause of a lot of their comorbidities, but of the psychological comorbidities, so we can address those because it seems like we're better at curing diabetes than we are at the mental health issues. Yeah, it's not bowel obstructions and internal hernias, yeah.
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