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#216 - 🫁 A Better Understanding of CDH - ft. Dr. Neil Patel and Dr. Gopal

Hello friends 👋

In this episode, I had the pleasure of speaking with two passionate neonatologists, Dr. Neil Patel from the Royal Hospital for Children in Glasgow, UK and Dr. Srirupa Hari Gopal, a third year fellow at Baylor, about their work and research in congenital diaphragmatic hernia (CDH). We dove into what draws them to care for these complex patients, the evolving understanding of CDH pathophysiology, and the importance of multidisciplinary collaboration in optimizing management. Neil and Rupa highlighted how the traditional view of CDH as primarily a surgical problem with pulmonary hypoplasia and pulmonary hypertension has expanded to recognize the critical role of cardiac dysfunction.

Our conversation also explored exciting advances in prenatal care for CDH, including fetal endotracheal occlusion (FETO) to promote lung growth, with Rupa sharing insights from her experience at Texas Children's Hospital, one of the largest CDH centers in the U.S. We discussed the challenges of counseling families facing a CDH diagnosis and the importance of long-term multidisciplinary follow-up.

Lastly, Rupa and Neil shared what's on the horizon that excites them most in CDH care. From tailoring management to different disease phenotypes and revisiting long-held treatment paradigms, to establishing consensus definitions for CDH-associated pulmonary hypertension to facilitate research, and investigating the potential of physiologic cord clamping - their passion for advancing the field was palpable.

While I admittedly started the episode feeling hesitant to dive into this complex topic, Neil and Rupa's enthusiasm and insights left me energized and eager to learn more. I hope our discussion helps spotlight the incredible work being done to improve outcomes for newborns with CDH and their families.

Have a nice Sunday!


The articles covered on today’s episode of the podcast can be found here 👇

Hari Gopal S, Patel N, Fernandes CJ.Front Pediatr. 2022 Jul 1;10:911588. doi: 10.3389/fped.2022.911588. eCollection 2022.PMID: 35844758 Free PMC article. Review.


Hari Gopal S, Toy CL, Hanna M, Furtun BY, Hagan JL, Nassr AA, Fernandes CJ, Keswani S, Gowda SH.Front Pediatr. 2023 Feb 1;11:1101546. doi: 10.3389/fped.2023.1101546. eCollection 2023.PMID: 36816370 Free PMC article.


Deprest JA, Nicolaides KH, Benachi A, Gratacos E, Ryan G, Persico N, Sago H, Johnson A, Wielgoś M, Berg C, Van Calster B, Russo FM; TOTAL Trial for Severe Hypoplasia Investigators.N Engl J Med. 2021 Jul 8;385(2):107-118. doi: 10.1056/NEJMoa2027030. Epub 2021 Jun 8.PMID: 34106556 Free PMC article. Clinical Trial.


Patel N, Lally PA, Kipfmueller F, Massolo AC, Luco M, Van Meurs KP, Lally KP, Harting MT.Am J Respir Crit Care Med. 2019 Dec 15;200(12):1522-1530. doi: 10.1164/rccm.201904-0731OC.PMID: 31409095


Hari Gopal S, Martinek KF, Holmes A, Hagan JL, Fernandes CJ.J Perinatol. 2024 Mar;44(3):354-359. doi: 10.1038/s41372-023-01845-8. Epub 2023 Dec 9.PMID: 38071241


Zani A, Chung WK, Deprest J, Harting MT, Jancelewicz T, Kunisaki SM, Patel N, Antounians L, Puligandla PS, Keijzer R.Nat Rev Dis Primers. 2022 Jun 1;8(1):37. doi: 10.1038/s41572-022-00362-w.PMID: 35650272 Review.



Short Bio: Neil Patel is a Neonatologist at the Royal Hospital for Children, Glasgow, Scotland, UK. He has clinical and research interest in neonatal hemodynamic assessment and management, including specifically cardiac function and pulmonary hypertension in congenital diaphragmatic hernia (CDH).  He collaborates widely in the International CDH Study Group and CDH Euroconsortium.

Neil’s other interests are clinical innovation, and Family Integrated Care.

Neil is Clinical Director of “Hi” the Centre for Children’s Healthcare Innovation at the Royal Hospital for Children Glasgow, and Clinical Lead in the West of Scotland Innovation Hub.

He is a Visiting Professor at the University of Strathclyde, Honorary Clinical Associate Professor at the University of Glasgow, UK, and NHS Research Scotland Senior Fellow.

Short Bio: Dr. Srirupa Hari Gopal is a third year fellow in Neonatal-Perinatal Medicine at Baylor College of Medicine.


The transcript of today's episode can be found below 👇

Ben Courchia MD (00:00.921)

Hello everybody. Welcome back to the incubator podcast. It is Sunday. We are back with another interview. I am by myself today. Daphna has been pulled into the unit, which is something that is becoming a little bit more frequent for us and it's unfortunate, but I am very happy to be here and be joined by two amazing neonatologists. I have the pleasure of having in the studio, Dr. Neil Patel and Dr. Sri Rupa Hari Gopal. How are you guys today?

Srirupa Hari Gopal (Rupa) (00:26.334)

Good. Thank you for having us over.

Neil Patel (00:27.342)

Great, thanks Ben. Yeah, it's great to be here.

Ben Courchia MD (00:30.137)

I'm going to introduce you both so that the audience knows where you're from. Neil, you're a neonatologist at the Royal Hospital for Children in Glasgow in the UK. Obviously, your research interests are involved in congenital diaphragmatic hernia. You lead active collaborations within the international CDH research groups, including the International CDH Study Group and the Euro CDH Consortium.

You lead in the West of Scotland, the Innovation Hub, and you're an honorary clinical associate professor at the University of Glasgow in the UK. You're a senior NHS Research Scotland fellow and a Scottish Quality and Safety fellow. Rupa, you are a third year fellow at Baylor. We are very excited to grab you at this time where you're probably elated to finally be done with training and finally move into the world of attending neonatology.

Srirupa Hari Gopal (Rupa) (01:23.006)

Yep, yep, excited.

Ben Courchia MD (01:24.985)

I guess my first question for you guys obviously is when I was a fellow, one of my tasks was really to try to stay away as much as possible from the CDH babies. Like this was like, if I can, but you guys found an interest in congenital diaphragmatic hernia. You're passionate about it. You've made it your research interest. I'm just curious, how did that passion really develop? And can you tell us a little bit more about that? Maybe Neil, if you want to start us off.

Neil Patel (01:51.086)

Yeah, thanks Ben. I think it's interesting you kind of run, you feel you had to run away from those babies. I get that because that's also what is, it makes them, I think really the rewarding patients to also be involved with. I know we shouldn't play favorites with patients, but there's a reason why I think both myself and Rupa are attracted to them as patients who we want to help to support clinically and we want to understand their condition and help to shift.

share increased learning about that that we can apply to improve in their outcomes. And for me, the reason for that is because they are complex, you know, yes, it's the thing that kind of scares us to begin with, but CDH is a condition that affects the respiratory physiology, the cardiovascular physiology, the interactions between those two. And then of course, there's the surgical components to it. It brings in so many different modalities of treatment. It's a condition that is lifelong and where our optimal management in the

Srirupa Hari Gopal (Rupa) (02:27.358)

you know, yes it's the thing that kind of scared us to begin with but, see you each Tuesday.

Neil Patel (02:49.966)

pre -natal and early post -natal period has important implications. And I think there's strong parallels with other major significant conditions that we treat in the neonatal unit, including extreme prematurity in that regard. So there's so much to understand. There's so much to challenge us and for us to develop skills in managing this population. But there's also so much room for continuing improvement. And for me, that's why they're the...

Srirupa Hari Gopal (Rupa) (03:03.294)

So, this is so much fun to start. It's so much fun. You guys can trust me without skittling.

So, so much room for improvement. For me, that's why I...

Neil Patel (03:16.462)

patient group that I'm really interested to go to rather than scared to run away from.

Srirupa Hari Gopal (Rupa) (03:19.054)

Yeah, yeah, for sure. I feel like there are two commonalities, if you will, that I see in how CDH is managed. I feel like one thing is that you have all the organ systems that are involved. Like it's, yes, the car, the cardiac and the lung pathology. And it just takes, takes you back to medical school where you're like so appreciative of this.

Ben Courchia MD (03:22.361)

I totally get that. Rupa, is this the same for you? Is this the complexity that...

Srirupa Hari Gopal (Rupa) (03:46.014)

physiology and that physics in blood flow that goes through. And so you're just like so, I just like love that physiology and just talking about it so much. And you also not just have the heart and the lungs, there's importance these days given to the brain, it's given to the gut, it's given to all these things, just like other neonates, but the physiology is just so fascinating.

The other reason I love CDH is also the fact that you just are interacting not just with one team, you have several teams that you're talking to. You're talking to the surgeons, you're talking to sometimes the pediatric intensive care unit, you are talking to your nurse practitioners. There's just so much of collaboration that happens. You're talking to the pulmonary hypertension, the cardiologist. So it's just a lovely, lovely area of neonatology that you just get to interact and learn from so many people.

Ben Courchia MD (04:35.673)

Mm -hmm.

Srirupa Hari Gopal (Rupa) (04:36.222)

that I think as a fellow for me was just so rewarding just getting that experience and inputs from such different aspects of medicine and still like, you know, being a part of that team was just what was rewarding to me. So yeah.

Ben Courchia MD (04:50.905)

Yeah, it's very cool. I'm sorry, I remember as a fellow, we had a patient on ECMO. And I think maybe I was traumatized by this as a first year. Like my medical director, Dr. Dora, I was on call at night. She basically showed me where the crank for the ECMO machine was in case I could break. And I was like, what do you mean? And she's like, well, if it breaks while they bring the other one, you're going to turn this thing. And I'm like, holy moly. But it's true. I mean, I was kind of joking around because the complexity is definitely something that's very...

attractive when it comes to managing these patients and they really challenge our understanding. Can you tell us a little bit then? I think we sort of always understand the defect that is involved in congenital diaphragmatic hernia, yet the challenges that this defect presents, like you said, involve so many organs. So what is the way that we optimize? How do we optimize these patients and what are our immediate

objectives and priorities. And how has that evolved over time? I'm just curious about that as well.

Srirupa Hari Gopal (Rupa) (05:56.606)

Yeah, Neil, do you want to go first?

Neil Patel (06:00.046)

Yeah, I can maybe I suppose it's interesting because when I first started to think about diaphragmatic hernia, you know, when I was a very young fellow, I think like everybody, I started with the surgical perspective of it. It's obvious these patients have a hole in the in the diaphragm that needs to be surgically corrected. And I suppose historically that was that was always the first challenge for these patients. When you go back to the original reports of their early of their management in the, you know,

mid to late 20th century, it was focused on that surgical management. And over time, I think it became quite clear that there's a respiratory component to these patients with the small lungs. You know, macroscopically, we can see they've got a small lung on the affected side and they've got pulmonary hypoplasia, microscopic level on the other side as well. So pulmonary hypoplasia was pretty, you know, embedded as a component of CDH. And then alongside that, these abnormalities, these are the pulmonary vasculature, you know, thickened.

hypermuscularised pulmonary arterioles, which we understand are going to be one of the main causes of pulmonary hypertension postnatally in these babies. So that's really been the model, I would say, historically of CDH, pulmonary hypoplasia, pulmonary hypertension due to these abnormalities of pulmonary vasculature. But I think the journey that has been happening during Rupa and my kind of careers.

And that has interested us as well is how the heart fits in there. So it's bringing this third part into the disease model as well, certainly in terms of the postnatal pathophysiology. So we now have this concept of a tripartite physiology, you know, the pulmonary hyperplasia, the what we call precapillary changes in the pulmonary vasculature, and then something happening to the heart as well. And yeah, it's great that we've been.

Ben Courchia MD (07:47.417)

Mm -hmm.

Srirupa Hari Gopal (Rupa) (07:48.478)


Neil Patel (07:50.254)

able to explore that a bit more and start to apply some thinking around that. And Rupa's been someone who's been really interested in that as well.

Srirupa Hari Gopal (Rupa) (07:56.062)

And I think that in the same realm of things that Neil was kind of explaining, basically the way I have started looking at CDH is three different phenotypes. And we can kind of go over those phenotypes a little bit. The first phenotype being those that don't necessarily have this dysfunction, the cardiac dysfunction that you see. It's just mild, they do pretty okay. Once you repair the defect, they're fine. And the main...

priority for these babies is gentilation, if you will. I love that term. I just like, since I started neonatology, that's been my favorite term. It's just gentilation. Just make sure that it's a low stem environment for them. Just make sure that their peep is not too much or not too less. And, you know, it's cruise control after that. That's what I think about. And then you repair the defect and these babies pretty much have good outcomes. And then you have the second phenotype where these babies actually have

Ben Courchia MD (08:44.185)

Mm -hmm.

Srirupa Hari Gopal (Rupa) (08:53.63)

bad pulmonary hypertension. And so it's the RV that gets attention. It's the RV that dilates. It's the RV that has that hypertrophy. There's a lot of afterload that the RV faces. And so those babies, it's pure pulmonary hypertension management. Give them appropriate FiO2, maybe trial, inhale nitric oxide. The other thing that actually connected me and Neil was the use of prostaglandins. And that's how actually me and Neil started talking and interacting. And

I never, as a resident, as a pediatric resident, never could imagine PGE being used for pulmonary hypertension until I actually became a fellow. And I was attracted to that physiology. I'm like, great. So you can start PGE. So that's wonderful. So the duct is open and the duct has a lot of advantages for acute pH management. And I couldn't imagine that until I actually became a fellow and was at bedside and managing these babies.

And starting PGE on these babies can help essentially get that duct open and act as a pop off for that failing right ventricle. And so that RV feels better in a way, and also this duct is open to help and augment your systemic blood flow. And prostaglandin also has a pulmonary vasodilatory property too. And so that kind of has like this triple effect that you can use. Of course, you can trial these babies on inhaled nitric oxide.

Oxygen is a beautiful drug. It can also help vasodilate. And if these things don't work, then you can go up to your next tier two medications like sildenafil and go on those pathways as well. And then you have this third phenotype, which is another big phenotype that's getting a lot of attention that I feel like Neil has done so much of research on and am so interested in that phenotype is babies that actually have primary LV dysfunction and their left ventricle is...

not doing so great. And these babies present with a sort of a post capillary pulmonary hypertension, if you will, because all of that blood coming to that left ventricle, because it's failing, just pretty much regurgitate backs, regurgitates back to the left atrium and causes a post capillary component of pulmonary hypertension. Now those babies are interesting because those babies are a little challenging to manage. And I think just streamlining the best medications for phenotype one, two versus three.

Srirupa Hari Gopal (Rupa) (11:15.55)

is just a challenge that every clinician faces. And I think that's probably why CDH is so fascinating, because you never know which phenotype you're going to face until the baby actually presents. So.

Ben Courchia MD (11:29.657)

It's so interesting that the heart gets mentioned so much in both of your answers right now, because there may be a temptation to think that, well, we're going to fix the defect and the heart is under stress because of things being out of place. But maybe once everything, as you were mentioning, Rupai, maybe like in this first phenotype, maybe everything will get better. But what we've learned from recent studies that actually you were involved in is that...

this cardiac dysfunction is an independent risk factor for increased mortality. And so can you tell us exactly a little bit about that data, but also about what did that mean for how aggressive we are becoming with the approach to cardiac management, whether it is hemodynamics or any other intervention? Neil, go ahead. Yeah.

Neil Patel (12:20.014)

Sure. Yeah, thanks, Ben. I think it's really interesting. I mean, both of us are heart obsessive in CDH. We have to put our hands up to that, I think. But we do recognize that there's other organs there and we try and have a little bit of a holistic approach. But it's just been fascinating to understand more the importance of the heart. And studying it has been challenging because as with any investigations in CDH, you know, this is a rare condition. And one of the...

One of the plus sides of that is that we have to collaborate and international collaboration has been key at helping us to understand the heart and its significance in CDH. And the investigation that you mentioned was one that we performed within the CDH registry, which is managed by the International CDH Study Group. And that's led by Kevin Lally and Pam Lally and Matt Harting out of Texas with their colleagues there. And really, I mean, we this investigation showed the

and importance of international collaboration, but also the foresight of those people who set up the registry, you know, many years ago and accumulate the data and it allowed us to look at a specific question of the relationship between early cardiac function and CDH and postnatal outcome. And we had 59 submitting centers from across the world who provided data on over 1100 babies where we were able to classify their cardiac function. And we actually asked the submitting centers to do that themselves. And that flags up.

of the really interesting areas, which is how do you define cardiac dysfunction or function and CDH, let alone any neonatal condition and Rupa is really helping us to address that as a question.

Srirupa Hari Gopal (Rupa) (13:49.246)

That was really interesting.

Neil Patel (13:59.918)

For the nature of that study, though, we had them classified according to cardiac dysfunction. And what we were able to see was that in the motivated analysis, first of all, left ventricular dysfunction and biventric dysfunction were independently associated with non -survival and with ECMO use. And that makes left ventricular dysfunction an independent predictor alongside some of the really established things that we know affect your outcome in CDH, your birth weight, your gestation.

the size or stage of your defect, as we call it, the liver position as well. So it was a really important analysis, certainly from my point of view, in helping us to really get cardiac dysfunction out there and appreciate it as a key mediator of the disease pathophysiology and of outcome. And then the next question that comes from that is, OK, how are we going to apply that in the clinical setting? And there's...

Srirupa Hari Gopal (Rupa) (14:38.142)

and we'll be back with more so that we can help the rest of the week better. Bye guys.

Neil Patel (14:58.19)

so many factors that then come into play there. First of all, how do we engage our colleagues, particularly ones who see the heart sometimes as a bit of a black box, very understandably, because how do we study it clinically? When should we have a look at it? How should we have a look at it? Who should have a look at it? And how are we going to use that information to affect our decision making, hopefully for the better? And that's been the kind of ongoing stages we're continuing to think about right now.

Srirupa Hari Gopal (Rupa) (15:27.39)

And I think the biggest challenge also piggybacking on what Neil was saying is just timing of echocardiogram. Like I feel like we all very correctly just are worried of CDH babies. They can get unstable pretty quickly and you can have a baby that had a pretty okay postnatal course in the delivery room and can pretty much decompensate as soon as you get to the NICU. And so because of how unpredictable and unstable these physiologies can be,

I think just convincing any bedside clinician to spend about 45 minutes to perform an echo might be a very big challenge. And I think that is where there is variability in practice and that is something we need to acknowledge that yes, we can provide data, but I think the first ever question we need to answer is, well, when is the right time to get that first echo on these babies? And we do know that babies with or without CDH can have that RV dysfunction to start with as they transition from

fetal to neonatal life. And so too early can be challenging, too late can be challenging. So it is a question that's also very difficult to answer, as Neil rightly pointed, that it's a rare disease. So it's all based on collaboration. It's all based on inputs from all these centers. And so that's, I think, the biggest question that we all struggle with as to when can we assess these babies. And if we do assess these babies,

do we start medications before because they might be unstable really fast and really quickly. And so I think that's where the biggest challenge I personally have as a clinician too. Like I just don't know when is a good time to get that echo.

Ben Courchia MD (16:58.457)

Mm -hmm.

Neil Patel (17:08.558)

And it's such a really interesting question that as well, because it's something we're trying to understand about when is the right time to start to phenotype these babies as Rupa was talking about before, you know, identify what their initial phenotype is and use that to guide management. I mean, there's some really interesting examples, you know, for example, the team in Denver who take a really proactive approach in performing echocardiograms in the delivery room. And we've got some really nice data that's come out from...

Michelle Yang, Bradley Yoder and their group in Utah recently, where they've actually framed it in a different way and moved to a later echocardiogram, which as part of a package of care was associated with improved outcome. And I think what they're really highlighting there is that taking, you know, a long time to do a really detailed structural echo alongside a functional assessment is something that we worry destabilizes a baby and especially these really fragile babies. So,

from a practical point of view, we're still trying to resolve this question of, OK, how are we going to evaluate them, but do it in a way that is really productive, doesn't destabilize them, helps us understand what's that cardiac phenotype, how we're going to treat it. And I think the other thing that we were understanding is the dynamic nature of these phenotypes, you know, that often it's early left ventricular dysfunction that appears first. And then that's a that's a sort of transitional phenomenon that then phases into

worsening right ventricular dysfunction. That can happen over the first hours or days. So we've got to be on our toes and that will very significantly impact a shift in treatment as those phenotypes change.

Ben Courchia MD (18:46.949)

And it seems that from what you guys are talking about, that this is definitely the next frontier for hemodynamics, where we can do these quicker ultrasounds at the bedside, where experienced team can do them quickly, repeatedly, and then have a handle on a very dynamic physiology that is constantly evolving so that you can stay in sync or in phase with your patient.

Do you think that these hemodynamics guys are coming to the CDH world in their spare time now? OK.

Srirupa Hari Gopal (Rupa) (19:22.558)

I'd hope so. I really hope so. But like I said, I think because CDH management involves a lot of people, I think that the buy -in also has to come from a lot of people too. So I obviously don't want to upset my surgeons by getting the baby unstable just a few hours before the surgery. So I do want to make sure that there is buy -in on why we're doing these assessments, why we're doing, you know, why we specifically need to get.

Ben Courchia MD (19:41.817)

Mm -hmm.

Srirupa Hari Gopal (Rupa) (19:49.822)

data before we actually get that baby's surgery done. And I think there's a lot of buy -in from so many other people too. So the nurses, nurse practitioners, there's just all of them that need to be involved and agreeable to getting that echo because these babies can get very sick from our experience. You just put that little probe and that's it. I don't know what happens with these babies. So I think that's the challenge. It's a good challenge to have, but it's also something that can...

Ben Courchia MD (19:53.817)

Mm -hmm.

Ben Courchia MD (20:06.425)

or we know.

Srirupa Hari Gopal (Rupa) (20:17.246)

that has to be taken with a grain of salt as we interpret these studies.

Ben Courchia MD (20:20.793)

Yeah, for many of them, it feels like they're walking the tight rope and any imbalance will really throw them off. It's interesting that you've mentioned already several times, Rupa, the concept of collaboration. And I think that over the years, we've seen that this multidisciplinary team has expanded, not just in the neonatal period, but now even in the prenatal phase. And so I'm wondering if you guys can tell us a little bit about how the management of these babies has changed prenatally, because there was a lot of expectant management before where we would just like...

Srirupa Hari Gopal (Rupa) (20:24.638)

Yeah? Yep. Yep.

Ben Courchia MD (20:50.521)

measure the lungs and hope for the best, maybe deliver early. But today there's a lot more work that can be done both from an interventional standpoint, but also from a counseling standpoint where we are counseling these families much earlier on. Can you tell us a little bit about how that piece of the management has changed?

Neil Patel (21:08.654)

Sure, Rupa. Okay. Well, I suppose it's the advent of fetal therapies that has really been exciting in CDH and got a lot of attention for everyone, hasn't it? And we haven't established fetal therapy now. It's fetal endotracheal occlusion where a balloon is inserted into the trachea to plug the lungs. You know, it's called lung plugging and try it and promote lung growth. The...

Ben Courchia MD (21:09.049)

Go ahead now.

Ben Courchia MD (21:38.329)

And for, for, I'm sorry, I'm going to interrupt you, but for people who are not familiar, right? I mean, you, you described the first half of the procedure where you include the trachea and hopefully by that, by increasing the pressure inside the airway, it will sort of help the lung push down more distally and grow better with eventually the prospect of the removal of this balloon prior to delivery around 34 weeks. Okay.

Neil Patel (21:38.702)

That... Yeah.

Neil Patel (21:44.59)

Yeah, yeah, yeah.

Neil Patel (21:50.702)


Neil Patel (22:00.974)

Yes. Yeah, that's absolutely right. So that's the second step, which is removal of the balloon. And of course, we know that the procedure itself is also associated with increased risk of preterm birth. So within that population of fetal treated CDH fetuses, there's increased preterm delivery and we have to balance the potential benefits against those risks. And I mean, what's been one of the really remarkable trials in CDH in recent years has been the total trial, which...

Srirupa Hari Gopal (Rupa) (22:01.946)

Yep. Yep. Yep.

Neil Patel (22:30.222)

led by Yanda Preston colleagues has looked at the efficacy of this approach, both in the severe CDH group and the moderate CDH group, with that severity categorized based on the fetal lung volume, you know, which we know can be assessed through ultrasound and all through MRI. And those trials reported a benefit in the severe group. In this study that was focused on the moderate group, the same benefits were not seen in terms of postnatal survival.

Srirupa Hari Gopal (Rupa) (22:53.662)

in the study that was focused on the moderate group, the same benefits were not seen in terms of post -mortem survival. But there has been some subsequent data analysis that perhaps suggests that earlier...

Neil Patel (22:59.694)

But there has been some subsequent data analysis that perhaps suggests that with earlier intervention, those benefits could have been seen in a moderate group as well. That said, I think that there's ongoing discussion around both the applicability of that evidence to different populations, especially higher performing centers that maybe already had a higher survival than was observed in the study groups.

And the other applicability is more practical. Is it possible for every family to travel to a fetal center, to have the procedures, to remain close to the fetal center for both the removal of the balloon and then subsequent delivery? And that's actually one of the challenges we see in our own center here in Scotland, where families who won't have that procedure have to go down to London for it. And that means, you know,

Srirupa Hari Gopal (Rupa) (23:34.686)

to have the procedures to remain close to the feeder center for the delivery, for the removal of food and then subsequently for the delivery. And that's actually one of the challenges we see in our own center and here in Scottham where the families who won't have that procedure.

Neil Patel (23:50.478)

for a substantial part of their pregnancy, moving their lives, you know, and disrupting their lives and all of the other practical factors around that. So from a technical procedure point of view, yes, absolutely possible. Yes, benefits being demonstrated. But of course, we have to think about the family and the wider implications. And as always, everything is a very personalized decision and approach. And I think what it also hints at, though, is the other potential for fetal therapies. And...

even within the concept of FETO, there are some really neat emerging technologies, including balloons that don't need to be removed, but they can be deflated within the fetus. And there's a really interesting work with a balloon again developed by Yanda Perest, Alexandra Binaki and their colleagues, where basically the balloon is deflated by being within a strong magnetic field. So you take the mother at that.

Srirupa Hari Gopal (Rupa) (24:34.742)

So you take the mother at that temperature station into an MRI room and you walk around the MRI scan and see that the temperature is...

Neil Patel (24:44.75)

appropriate gestation into an MRI room and you walk around the MRI scanner, she doesn't even have to go into it. She has to walk around it. The balloon will deflate. And that's that, you know, that removes one of the big risks, which is the second procedure to remove the balloon. So that's really cool. And then there are other combinations of potential phytotherapies that are being considered both with phyto and in other settings as well.

Ben Courchia MD (24:53.593)

That is so cool.

Srirupa Hari Gopal (Rupa) (25:04.414)

Yeah, no, I piggybacking on what Neil was mentioning, I think that here in TCH and Texas Children's, we do perform FEDO. And so rightly said, our collaboration pretty much starts prenatally. And there's like all of these people that get to meet with the family. And it would include the neonatologist, it would include the surgeon.

course, there is like a fetal surgeon, a maternal fetal medicine physician as well. And so all of them together counsel the family and every effort is made for them to transition to Houston if they were interested in the procedure and if they would like to continue care here. And of course, the delivery would have to be in a high resource center, which would be TCH here.

But every effort is made to keep these families comfortable. And of course, it is stressful, especially if the families already have other kids. It is a big decision to move all the way. But at the end of the day, I think every effort is made to keep the families comfortable. And the procedure itself is pretty cool. I've gotten to see a few and I've really enjoyed it. One of the fascinating days for me during fellowship was when we were taught as neo fellows how to deflate the

the balloon itself, which was such an interesting thing because you never know when these babies can deliver. As Neel was saying, these babies are at high risk for preterm delivery. And so if you are the neo -on -call and if you were right there and if you were given the fetoscope to deflate the balloon, just so that we all knew how to do it and just so that we played with it to understand the nuances of that whole apparatus, we were actually trained to do that. And so it's just...

Ben Courchia MD (26:30.393)


Srirupa Hari Gopal (Rupa) (26:49.886)

It's so nice to see technology being applied and as you rightly said, so many things have evolved in CDH management and it's just, I didn't even know about this whole magnetic field, so that's news to me, learned something today. So that's good. That's good. I know. Yep. Yep. So that's, it's, I think very nice to see.

Neil Patel (27:01.074)

Yeah, watch out for that. It's coming. Yeah. Yeah. Yeah.

Ben Courchia MD (27:01.801)

So now you're like in my shoes. I'm the one learning stuff live and on the podcast.

Srirupa Hari Gopal (Rupa) (27:12.926)

that evolution happen and it just feels good because you are interested in this disease pathology that there are great things that are gonna come and innovative things that are gonna be applied.

Neil Patel (27:14.958)


Ben Courchia MD (27:22.905)

One more question about, about FITO, obviously, because I think that from a counseling standpoint, the neonatologist has a huge role to play. especially when you look back at the data from the total trial, as Neil, you mentioned, I think the, the amazing outcomes compared to controls, that survival to discharge. And I think it was six months of age, which is like 40 plus percent.

Neil Patel (27:22.958)


Ben Courchia MD (27:48.121)

It's counterbalanced by really the risk of early labor, premature rupture of membrane, premature birth. And we have a lot of experience with that. And obviously it's not just, here are the odds of delivering a baby at 30 weeks. It's here are the odds of delivering a baby at 30 weeks with CDH. How do you counsel these parents in light of a new technology that's obviously very promising, but also having a serious potential risk?

What are some of the tips you could give us on how to appropriately counsel families when it comes to that?

Neil Patel (28:23.79)

Yeah, that's a great question. And I think the first thing is it's not a discussion to have on your own. You know, we have it with our maternal fetal medicine colleagues and with our surgical colleagues as well. So that families are getting a perspective of a whole team, not just one individual. And I think that's really important. I think it goes back to what I was saying before. First of all, it starts, I suppose, with understanding that family and what their situation is, you know.

how they've come to this pregnancy, how many other children they have, what their background is, because I think being able to fully share what the implications are, both of the procedure itself and that aspect, but also the long, the potential complication of preterm birth and long -term outcomes is tailored by an individual family as it is for any prenatal conversation. It's hard, I think, to...

give a full picture to any family of the complexity of CDH and then to add into that the complexity of preterm birth. And in what is what is a relatively short conversation where you're actually asking them to then make a decision and we talk about joint decision making and best ways to approach that. But I think again, it has to take into account what that particular family situation is.

Srirupa Hari Gopal (Rupa) (29:47.614)

Again, it has to take into account the current picture.

Neil Patel (29:53.71)

We would go through the risks of prematurity just as we would for any baby who's going to be born at those early gestations. But we have to frame that in the context of all of the things that we have to do for CDH. And I think one of the other critical things is understanding how prematurity may impact the potential, sorry, the risks of ECMO as well. First of all, the risk that you may not even be at an adequate gestation or size to have ECMO if you needed it.

And the second thing is that if you even if you were reaching those thresholds that your risks on ECMO would be much higher at those lower gestations, in particular risks of bleeding and then intramatricular hemorrhage, pulmonary hemorrhage and the other things that we really worry about babies going on ECMO. So we have to have an honest conversation. And I think the data is still coming through, to be honest, about what the burden or otherwise of prematurity and CDH associated.

with this fetal population is. And it's likely that we're also, as a community, gaining more experience as these babies are, as we're starting to see this, this, this additional cohort of preterm babies who've been fetal treated coming through as well. So it will be really important, I think, to continue to follow that up, including through the registry and other means to understand what, what, what are the short and long term implications of it so that we've got that information to share with families.

Ben Courchia MD (31:22.905)

I'm going to put a pin in that because I want to come back to that with you, Neil. But Rupa, any tips that you can share with us on how to appropriately counsel families in light of such a difficult decision?

Srirupa Hari Gopal (Rupa) (31:32.734)

Yeah, no, I think it's a very challenging thing to counsel families, especially when there's preterm involved in the mix of all this pulmonary hypoplasia and everything as well. I think as I think we pretty much covered all the points, but the one thing that I was going to stress about is just ECMO candidacy. And that is a whole, whole big discussion that happens in collaboration with the surgeons, with the whole CDH team and all of the people involved in caring for these babies as to whether these baby, this particular baby who's potentially going to be preterm potentially has CDH could even

be a candidate, are the neck muscles even good enough for this baby to actually get cannulated? So those are questions that I think we might have to like discuss and, you know, share with the family. And I think that is a very, very informed decision to, you know, either go with the procedure or not. And there's so many factors that take into account. And I think that's where having a lot of input from various aspects of medicine is helpful for the families as well.

Ben Courchia MD (32:28.697)

Thank you.

Neil Patel (32:28.718)

Yeah, and I think, yeah, just as you're saying that, Rupa, I mean, it just goes back to that question of we're giving so much information to these families, first about diaphragmatic hernia, secondly about prematurity, thirdly about this really complex treatment, ECMO, and all of the risks associated with all of those. I think it's the other really important thing here is having this kind of ongoing discussion with the family so they can take that initial information away and then replay it back to someone. And that's where I think it's not just

the clinical team that become important, but also if there's a great patient association who can help to connect them with other families, because they're going to go to the internet, right? And they're going to look at who else has been in this situation and they're going to have to try and then take that information into their decision making as well. So it's having those people who can help them navigate that decision is the most important thing, I think.

Srirupa Hari Gopal (Rupa) (33:22.11)


Ben Courchia MD (33:22.169)

And so I think that's an interesting point because the, we mentioned the, the total trial, which if I remember came out in 2021, but I guess what I'm getting from your answers is that number one, this is a procedure. So technically we have the potential to get better at it. And technically maybe there's even a hope that despite the great numbers that have already been reported, these numbers might continue to go up in terms of survival to discharge survival to six months. And who knows, maybe the risks might also go down. So.

Is that a hope and do you think that this is well founded and is this something that maybe you're already starting to see a signal of, especially in the collaborative effort like the CDH hernia study group that you're already seeing maybe that the numbers actually improve with more experience on both fronts?

Neil Patel (34:10.35)

And yeah, it's not because I'm not performing the procedure and because we don't do it in our own center. I would let experts who have been doing more of these and are looking at the data of the known center and then can buy compiling that with others comment on that. I think it is going to be really interesting to see if the if there's a dynamic nature to the outcomes, you know, as there's increasing numbers and there's always going to be some patients where it's not appropriate.

Ben Courchia MD (34:20.921)


Neil Patel (34:39.63)

including those ones who are diagnosed at a later gestation as well, or with other abnormalities or associated anomalies. So it's not as if we are going to move to an era where FETO is potentially there for every CDH case. And I think we have to have to bear that in mind that we're still going to have to think about improving outcomes for non -FETO patients as well. But in terms of the technical ability of it,

And the impact of that, I think it is going to be interesting to see if there's if there's continuing evidence that that is having an improving impact. The other thing is, as I mentioned, I briefly kind of mentioned as well, there's there's a lot of interest in other potential for therapies that could be combined with fetal or independent of it. So, for example, there's interest in is there medications that can be given to the mother that may modulate the?

the development or mitigate the abnormalities of pulmonary vascular development or even cardiac development. There's some really interesting work coming through on the role of extracellular vesicles, which are potential carrier of microRNAs, which have also in the past been shown to be potentially involved in the genesis and mitigation of CDH. And I think, you know, as we explore in animal models at first, but then think about how that might translate.

we're talking about not just FETO alone, but FETO in combination with pharmacotherapies, pharmacogenomic therapies. That's an exciting prospect for the future. It's also one that needs to be kind of really carefully and appropriately researched and applied. And I think we're also moving into an era where we might start to understand different genomic phenotypes of babies. And I know...

Srirupa Hari Gopal (Rupa) (36:23.55)

I think we're also using it so we are aware. We might start to understand it a little bit.

Ben Courchia MD (36:28.665)


Neil Patel (36:30.894)

David McCully and colleagues from your kind of sister podcast, David is a real pioneer in that area. And it's going to be really interesting to see how their learning can be applied to this as well. So, yeah, we absolutely need to follow those patients through and continue to use the mechanisms we have of collaboratively collecting and analyzing data to do that. But I can see us starting to add adjuncts to FETO in the future.

which may be part of how we see an ongoing improvement and impact.

Srirupa Hari Gopal (Rupa) (37:04.542)

I do want to mention in the same realm of things that we do perform fetal and it's become a lot more common to perform because we do talk about it in VR referral center. So we get a lot of babies that are referred from elsewhere as well. We did publish this data on both moderate and severe, I think back in 2021, if I remember correctly, where we actually showed there was improvement in pulmonary hypertension at discharge. Now, I think.

One thing that I want to mention that again brings up the question, what do you define pulmonary hypertension? We can kind of segue into one of the other big things that me and Neil are interested in understanding is because this is a multidisciplinary collaboration, what pulmonary hypertension means to a surgeon, what pulmonary hypertension would mean to a neonatologist, and what pulmonary hypertension would mean to a pulmonologist or a cardiologist are completely different.

they are different and we need to acknowledge that there are differences in how we as neonatologists at bedside can look at a baby and be like, that baby's in pH crisis without an echo. We can actually just decide based on how the baby's saturations are and how the baby's overall presenting. I think that one of the big things that me and Neil are working on is to, we actually did a systematic review recently where we looked into the existing literature on CD8 studies.

Ben Courchia MD (37:58.329)

Mm -hmm.

Srirupa Hari Gopal (Rupa) (38:26.622)

which had a definition of pulmonary hypertension or cardiac dysfunction in their papers. There were about 7 ,000 papers that had evidence on CDH and we formed sort of an international hemodynamic collaboration together. And we basically came down to a total of 113 papers. And out of the 113 papers, what was interesting to me was about 69 % of the papers actually had a definition of pulmonary hypertension. But...

27 % of them did not actually have any definition. So it kind of like baffled both of us because we were like, huh, that's interesting. It is interesting that we talk about pulmonary hypertension and CDH, but then what is defined as pulmonary hypertension and CDH? We do have the American Thoracic Society that has definitions for pediatric pulmonary hypertension. But then what is...

CDH -associated pulmonary hypertension. So that's something we're trying to decipher. And interestingly, one of the most common definitions that's used for all of us is one that was provided by Dr. Keller et al. And this was a paper that came back in 2010, basically dividing pulmonary hypertension based on three echocardiographic parameters. That would be your ductus arteriosus flow and velocity, your...

Ben Courchia MD (39:34.937)

Mm -hmm.

Srirupa Hari Gopal (Rupa) (39:40.894)

the IV septal position and your tricuspid regurg. And then they sort of grade the pulmonary hypertension into greater than two -thirds systemic, two -thirds systemic to systemic, and systemic to supra -systemic. So that's the most commonly referenced definition. But we are trying to collaborate with different people and perform a Delphi process to come up with consensus guidelines on definitions for pulmonary hypertension. So the reason I bring this up is because...

We have all of this data out there, but what is pulmonary hypertension? And it means different for all of us. So I think that's something that we need to acknowledge. And again, take that with a grain of salt. So we're going to the basics, unfortunately.

Ben Courchia MD (40:22.489)

I'm laughing because in the process of trying to solve a very complex problem, you then stumbled on an even bigger problem of like, how do we define pulmonary hyperdense? my Lord. This, this.

Neil Patel (40:27.694)


Yeah. Yeah. Yeah.

Srirupa Hari Gopal (Rupa) (40:30.462)

Yep, absolutely. Yep, we're all going to the basics now. So I feel like it's just, let's just start with the first question before we go into all these big fancy questions that we all have. And that's not wrong, but let's just solve this basic issue first.

Neil Patel (40:35.374)


Ben Courchia MD (40:47.193)

especially as you guys mentioned in the beginning of the episode where collaboration is the key. And so in order to collaborate, we need to speak the same language. We need to understand and think about it in the same way. Then otherwise, what is the point? So you're absolutely right. And if you didn't do that, I like this analogy of always, this is the kind of work that I like to call like building the highways where it's not a pretty job, but like it's essential for, for proper moving of, of ideas and so on. And it has.

Neil Patel (40:53.742)

Totally. Yeah. Yeah.

Ben Courchia MD (41:13.369)

years worth of value. So it's sometimes like, my God, I can't believe we're going to have to spend time doing this. But on the other hand, it's essential for the future of that work and of that research. That's very cool. We have a few minutes left and I wanted to address a topic that we may not have enough time for, but anyway, we'll try to do our best because I think that as we were talking about prenatal counseling and we were talking about management inside the NICU, there are a lot of questions from parents.

Neil Patel (41:23.342)

Absolutely, yeah.

Ben Courchia MD (41:40.313)

in the NICU about what is going to be the long -term prognosis? What's going to be the quality of life for my baby surviving CDH? And I'm just wondering if you can tell us a little bit about how do you approach that question from parents, both from a risk stratification and then what are some of the commonalities of all these infants? They will sort of all have to struggle with one thing or another. I think one of the things that we all think of first is that after everything's repaired, they're going to have some pretty...

non -negligible GI issues that we've all had this baby post -correction that has a lot of reflux and so on. But how do we appropriately counsel families for things they can actually anticipate post -intensive care in the case of CDH? Neil, I see you're nodding heavily. I'm going to let you take that first.

Neil Patel (42:27.854)

Yeah, yeah, no, it's it. Well, it's a really good question. And it's one that I suppose I'm trying to answer for myself every time I'm speaking to a family of diabetic hernia. How much information should we be sharing at every point in the journey? And of course, we want to be fully open and honest because it is a long journey for these for these children. And and as they become young adults and adults who are continuing to understand what the challenges they might face. And I think certainly in the prenatal and early postnatal period,

tend to focus on what they're going to experience in that neonatal journey. And we talk about the different therapies that we might be using, including in the more severe cases, the role of ECMOs of potential there. But you're absolutely right. Once we're getting through that perisurgical period, and then I think we've got to start thinking about the complications that can arise or the ongoing issues.

through infancy and into early childhood. And we know from families themselves and from studies that have been done with families themselves that one of the biggest issues for them is around feeding, nutrition and growth. And I think sometimes when we're focused just on the neonatal period, it's easy to overlook that a little bit, but there's been some really nice analysis done led by CDH UK, who are the patient association charity here in the UK.

but also more recently with some priority setting work that's been done by a group of Trisha Prentiss and colleagues in Australia with the James Lind Alliance, where they've worked with families and with clinicians to say, look, what are the priorities for research? And yes, that's identified the priorities for research, but it's also given us a window on what are the things that for the longer disease course are important to families. And that's really helped me frame those conversations with families a little bit better.

Srirupa Hari Gopal (Rupa) (44:02.11)

and mental violence where they work with families and clinicians to see what other priorities they...

Ben Courchia MD (44:17.753)

Mm -hmm.

Neil Patel (44:22.51)

particularly thinking about growth and nutrition. And of course, families also just want to know about the normal things in life, you know, going to school, playing, you know, and interacting with their kids, playing sports, living at home or living independently, all of these kinds of questions. So I think, again, sometimes it's about turning it back on the family themselves, say, what's the thing that you're most concerned about for the future?

And that's not specific to CDH. I think it's a good question we can ask any family. And rather than me assuming what's on their mind and what they're worried about, trying to get to the things that are on their minds. We've had certain cases where patients have had surgical complications following CDH repair. I'm talking here about adhesional obstructions, CDH recurrence, which we know is a risk. And I think it's important to counsel families about those and not just to...

assume that the diaphragm's been repaired, you know, in the initial period, it's going to be smooth sailing for the next few weeks, months, year or two, but to really be clear to them about what the ongoing risks are. And the other thing that we really stress to our families, and we've got a great service that colleagues helped to run in my centre, is a multidisciplinary CDH follow -up clinic. And I think being able to reassure them that we've got a mechanism that is going to see them regularly, that is going to check on all the kind of areas that we're worried, that we're worried they may need some support in.

Ben Courchia MD (45:38.105)


Neil Patel (45:48.974)

just helps, I hope to give them the reassurance that yeah, we're going to be looking out for these things with you. And that's a really important part of a service for these patients to follow up.

Srirupa Hari Gopal (Rupa) (45:59.422)

I agree. I think the follow -up part helps them feel at ease because there is multidisciplinary clinic that exists here too. And we make sure that they're hooked up even if they are from out of state, we just make sure that they have appropriate follow -ups and they are followed through. It's hard to counsel people, especially when they're overwhelmed enough knowing that there's this surgical defect that their fetus has. And so that is always a little bit of a challenge to like...

as Neil was saying, like, what is it that they want to know as opposed to what is it that you want to tell them? And like, you know, you don't want to cause too much of anxiety because they're probably overwhelmed and anxious themselves at that point. And so I think the main focus is that that would be good for parents to know about is the possibility of ECMO, the possibility that that ECMO can have implications on how these babies discharge would look like. And the fact that these babies could have feeding problems.

throughout, at least in the first two years of life, I would think, just because of how their bowels all like in the wrong place, there can be implications to that. And of course, talking definitely about the pulmonary hypertension and how long it typically can last and that they would have follow up with all of these people in order to, you know, just be just feel a little at ease when they leave the NICU.

Neil Patel (47:17.23)

Yeah, and I think I think sorry, but I was just going to add to that. I think one of the things that we're that we're really looking to now is great that we've got multidisciplinary follow up in the in childhood. But then what about after that? You know, and it's been a big problem around who do we transition to to continue to look after young adults, you know, with CDH in the future. And there's been some great learning from colleagues, particularly in the Netherlands, who have been setting up adult CDH services now.

Ben Courchia MD (47:17.657)

Yeah, yeah, go ahead, Neil. No, no, no, no, don't, I'm sorry.

Neil Patel (47:46.894)

But it's something that I think we're going to have to look to, especially that we're moving into an era where many more children who had very severe CDH and who are ECMO survivors are becoming young adults and older adults as well. And we've got so much to learn about the problems that they may face in the future and how we can best support them as well. And just I had an interesting experience not very long ago where we had a CDH patient who was making really great progress and they had a little bit of a backward step.

you know, that's all part of the roller coaster of ICU, isn't it? And the family said to me, well, nobody told us that this might happen. Everything was going really well. And then we went backwards and nobody told us. And that kind of stopped me in my tracks. And I was kind of like, OK, let's sit down. Let me tell you about everything that can happen in CDH. And they wanted that at that point. And I kind of reflected, should I have told them all of that earlier? But I think it can be difficult for us to sense that when is the right time. Yeah.

Ben Courchia MD (48:45.241)

Yeah. And also who do you have in front of you? Some parents wanted to say, I know that even my full term kid with no problem can cross the road and have a problem. I don't want to have to have all the risks laid out in front of me. But for some parents, it's like, I want to have the full gamut explained to me. So I think it's interesting that this individualized type of care also applies to counseling. Yeah. We're a little bit over time, but I wanted to, I guess...

Neil Patel (48:48.302)


Neil Patel (48:58.03)


Neil Patel (49:04.91)

Totally, totally, yeah.

Srirupa Hari Gopal (Rupa) (49:07.198)


Ben Courchia MD (49:12.121)

celebrate a little bit what Rupa has achieved so far, because I think, as we said in the beginning of the episode, you're a third year fellow and I think everyone, me included in the audience, will be impressed by your level of knowledge. And so I wanted to know how was it for you in fellowship to find a passion really and pursue it the way you've pursued it, to reach the point where you are today, where you're really comfortable with this topic, you speak in a manner that is passionate.

Can you tell us a little bit about what that journey has been like? Because I think if I was a trainee listening to you, I'd be like, how do I do the same thing?

Srirupa Hari Gopal (Rupa) (49:49.374)

You're being very kind, but my interest in CDH started in residency and I come from a smaller residency program, but a very mighty residency program. And so we, UT Chattanooga and Tennessee. So I'm a very proud Chattanooga person, so if anyone's hearing.

Ben Courchia MD (49:59.929)

Give us the name. There you go. Yeah.

Is it near Le Bonheur, right? I see. Fair enough.

Srirupa Hari Gopal (Rupa) (50:10.046)

So Le Bonheur is Memphis and we are at Chattanooga. So we do take care of CDH babies and the big thing that I always talk about is we did not have fellows. And so it was us residents being in the PICU, managing, being in the NICU, managing these babies. And so it was just a very nice experience there. And I came to TCH not knowing that TCH was one of the biggest CDH centers in the country. We get about 20 to 30 babies with CDH every year. So it's, yep.

Ben Courchia MD (50:22.297)

I see.

Ben Courchia MD (50:37.273)

Wow, a couple of months then, huh? Wow.

Srirupa Hari Gopal (Rupa) (50:39.198)

Pretty much. And so I think that that's how I came in. And my first block in fellowship as a first year fellow was in a team that was dedicated to CDH. And that was just very eye opening to me. And I think that's when I saw PGE being used and started researching about PGE. My mentor, Dr. Caraciola Fernandez, he established the CDH guidelines at Baylor. And so.

It just worked out okay. And I researched, I remember Neil and I reached out to him on research gate because I didn't know his email. I'm like, Hey, big fan of you. Can we please talk? And I think that I've just been blessed to like have all of these mentors, Dr. Sharada Gowda, Dr. Shazia Bomal, all of them have just been like very inspiring to like, you know, get involved in CDH. And I think just getting involved with Neil, I just like got my...

Neil Patel (51:14.638)


Srirupa Hari Gopal (Rupa) (51:32.958)

brains open to the cardiac dysfunction aspect of CDH. And I think we've spent hours on Zoom just talking and talking about this cardiac dysfunction. And I feel like it's just very nice to get that perspective.

Ben Courchia MD (51:46.073)

How cool is it that you're a fellow in Texas and you're able to actually meaningfully collaborate with Neil who's in the UK? And I think that's a lesson. And I want to, again, congratulate you on the work you've done and on the level of expertise you've reached. And whoever the hospital receiving you after fellowship will be very fortunate to have you as an attending. So congratulations for that. Yeah. Any parting thoughts before... What are you... I guess I'm going to ask a leading question.

Srirupa Hari Gopal (Rupa) (52:06.046)

Thank you.

Ben Courchia MD (52:16.313)

If I had to ask you what is the development that you see on the horizon that gets you really excited for the pathology itself and for the patients suffering from CDH, what do you think is coming down the pike that you're like, man, it doesn't have to be proven or anything, but you're just excited about finding out whether this is going to work, whether this is going to be meaningful, significant. Tell us. I'm going to let me begin.

Neil Patel (52:41.678)

OK, thanks. That puts me on the spot. You know, I think what's going to be the challenge is actually our revisiting our existing approach to CDH, you know, and Rupa gave this really nice description at the beginning, these different phenotypes that we're starting to understand. But that means that we got to move away from a one size fits all. You know, it's really nice when someone just says, OK, that's the condition. That's how you treat it. The flow chart is just one straight line.

But what we're seeing is, now hang on a second, the flow chart, you know, you've got to look, understand the physiology and then decide which side of the flow chart you're going to go down. But what's exciting about that is that we're taking some approaches, you know, whether that's use of pulmonary vasodilators, the role of ECMO. And we're saying, look, we can use these in a much more refined way. So it's not that there's bad meds. There's not things that are good or bad for CDH. It's about the right treatment at the right time. And...

Srirupa Hari Gopal (Rupa) (53:30.59)

So it's not that there's bad bits, it's not the things that they feel are bad.

Neil Patel (53:38.446)

That's a challenge for us to get that message across and then to generate the evidence to show that it works, because that doesn't lend itself to a simple RCT. You know, it's not a one or zero discussion. It's multiple options. So I think that's going to be a really interesting challenge in the immediate short term. And yeah, I think those novel therapies we talked about as well, you know, it's going to be interesting to keep our eye on the horizon, see what follows through there.

And that, you know, some salutary tales about, you know, things that looked really promising in the past, but that we needed to understand the complexities of how they may actually affect the physiology and also understanding what the individual patient response might be. So again, that's where the genetic aspects are going to be interesting to bring into as well. So that's, yeah, those are the things that I'm keeping my eye on. Yeah. Yeah. Yeah.

Ben Courchia MD (54:30.681)

Absolutely love that. Absolutely love that. I think you're absolutely right. When you have a problem that's frustrating and you realize that, hey, if we just think about it this differently, there's all these options that now suddenly all these doors open up and we have a lot more levers to pull on. I think it's just such an exciting feeling. So that absolutely resonates with me. What about you, Rupa? Anything that you're excited coming? Pick one. You'll pick two. Fine. Fine.

Neil Patel (54:47.694)

Yeah, yeah.

Srirupa Hari Gopal (Rupa) (54:52.638)

I have a lot of things that excite me that are gonna come. I will pick two, how about that? I will pick two. One, I think one of the things that I think me and Neil were talking about this is the physiological core clamping in CDH. I feel like there are a few centers that are doing it. And I'm very interested to know how that turns out. Because I know that in the delivery room, we're like, just get us the baby. We need to get that tube in as soon as possible. I think that is gonna be something interesting. And there's, I do think it's a pretty cool idea. And I do think that...

Neil Patel (54:55.694)


Ben Courchia MD (55:05.433)


Ben Courchia MD (55:14.169)

That's right.

Srirupa Hari Gopal (Rupa) (55:21.342)

That's going to open doors to a lot of new ideas and thoughts. And I do think that that is something I'm looking forward to. There are trials that are ongoing, and I'm very much looking forward to it. They have very cute names. I feel like Neil told me about this. This was chick and pink. Is that correct? Chic.

Neil Patel (55:34.926)

Yeah, Chic, not surprisingly, is the French trial, Chic, and then Pink is the other European trial led by the group of Rotterdam as well. So yeah, it's going to be interesting to see the effects of those. Yeah, they also just highlight the challenge of running trials in CDH as well. So they're significant for that.

Ben Courchia MD (55:39.577)

Of course.

Srirupa Hari Gopal (Rupa) (55:40.478)

Thank you.

Srirupa Hari Gopal (Rupa) (55:46.366)

Yeah. Yeah. For sure.

Srirupa Hari Gopal (Rupa) (55:53.878)

Yep. The second thing, I may be biased, but I'm looking forward to what our Delphi process on definitions comes up. I think that's going to be very, very important. And it's going to open doors to a lot of additional questions that will come into our way as well. So very much looking forward to that.

Ben Courchia MD (56:13.593)

That sounds great. And we'll look out for that paper whenever you publish it to review. Neil Ruppa, this was a phenomenal conversation. I had such a good time. I have a bunch of notes that I've written down. I have actually notes everywhere. I have notes on my computer that I've been typing. I have notes on my little notebook. This is all very exciting. I think you, I was reluctant to talk about CDH, but now I'm excited about CDH. So thank you. Thank you for sharing. That's right. Thank you so much. We'll put a lot of the links.

Neil Patel (56:16.91)


Neil Patel (56:25.742)


Srirupa Hari Gopal (Rupa) (56:26.43)

I'm gonna go.

Neil Patel (56:34.894)

okay, that's great. We've got a convert. We've converted you. That's great.

Srirupa Hari Gopal (Rupa) (56:38.59)


Ben Courchia MD (56:43.353)

to the papers that you mentioned in the show notes and we'll put away for people to get in touch with you so that you don't have to necessarily just rely on ResearchGate. But thank you both for making the time to be on with us today.

Neil Patel (56:52.43)


Srirupa Hari Gopal (Rupa) (56:56.254)

Thank you.

Neil Patel (56:56.846)

Thanks so much.


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