CDH Patch repair: patch material vs PSI muscle flap

OK. Welcome everyone. Um, this is, uh, uh, it's my pleasure to welcome you and together with, uh, uh, Martin Laer to, um, have you all for a new web seminar on uh controversial topics of pediatric surgery. Today we're gonna talk about uh one of the uh most controversial topics which is how to patch the diaphragm. babies that are born with a congenital diaphragmatic hernia, some of them, as you all know, have uh big defects that need to be uh patched, um, and, and, uh, there's different options, uh, and I don't think that there is any evidence that one option is superior to another. And so we decided to involve in this um webinar, uh, two experts on the topic. Uh, one is, uh, Professor Amuria Sasina, who um is our president, and the other one is, uh, uh, Professor Jose Luis, Luis Perro. Um, Martin, over to you to introduce Amelia will be the first, uh, speaker. Yeah, thank you, um, Amulia, and thank you, everybody. So we have the pleasure to, uh, to welcome Professor Amulia Sakena. Uh, he's a consultant of neonatal, um, surgery and pediatric surgeon at the Chelsea Children's Hospital in London. He trained and worked, uh, at, uh, major tertiary European and American medical centers, um, started with a research fellowship at the Boston Children's Hospital and gained Further experience at other very prominent surgery centers around the globe. His research um is focused uh in the area of tissue engineering and regenerative medicine. His, uh, scientific office is outstanding, presented over 450 papers at international surgical conferences, 180 articles, 75 book chapters. So, um, he's a true surgical teacher, uh, teacher to also a lot of us, especially in, um, Eastern Europe in recent years. Professor Saxena is, um, editor in chief of the, um, new Journal of, um, Pediatric Endoscopic Surgery. And has actually edited two books. Uh, one is Essentials of Pediatric Endoscopic Surgery and uh one book called Chest Wall Deformities. I bought them, both actually, and I did not regret it, uh, so far, so I can recommend both of these, uh, books. Um, finally, um, he's a president-elect of UUSA and a good friend, um, Amelia, it's really a pleasure for us to have you tonight and, uh, we are looking forward to your talk. So, I'll give you a small introduction on patches before we get into the topic of using muscles, and then of course we'll take your questions. As you know that CDH has an incidence of 1.7 to 5.7 in 10,000 births. This is also a variation depending on the geographical side that reports these cases. Management of CDH still, and I underline it, offers surgical challenges. Large defects require the utilization of prosthetic materials. And it is estimated that the patch repair in CDH is reported to be 30 to 50%. Now when you look at CDH in the past couple of years, focus has completely shifted from the surgical side. Most of the CDH is now reported on lung research, the hypoplastic lungs. ECMO also was taking a big precedence. Fetal tracheal plug also, you know, took the limelight, lung to hydration. And then in the 80s and the 90s, with tissue engineering. And then, of course, with the thoracoscopy coming in, the minimal access repair. But what happened in this time is that the surgical repair and as well as the patch selections were neglected. And these are two things which I will focus on in today's lecture. Now when you see the patch repairs, there's an inconsistency in patch repairs and congenital diaphragmatic hernia. First of all, we are not very sure about the type of patch material. We are not sure what type of patch to use. Do we use a dome-shaped patch, cone patch, or do we use a tout patch? There is no unanimity on that. Resection of the pleuroperitoneal membrane is very poorly reported in all the series that have been reporting their cases. Rib, anchor, or muscle sutures. This is also poorly reported. You always talk about the dreaded corner stitch on the lateral side, but on the medial side in large defects, where do you put the hitch stitch on the esophagus close to the aorta? These are structures which are very vital and in newborns it's difficult to place the stitch over there. And the patch failure. Very poor reporting. People just report that this patch has failed, but there's very little information. Has it ruptured or has it come out from the side? So this is also one thing which has not been considered. Now, the question which I ask mostly to myself also, what are we trying to replace in these large defects? As we know that the diaphragm is made of two parts, one is the connective tissue and the muscle. So, are we trying to replace the muscle, or are we trying to replace the tendinous part of it? And that is a question which we have not been able to answer ourselves while we do muscle uh replacements or we try to replace it with different patches. This has a lot of topics or subtopics. I think I will only cover the 1st 4 topics in my talk today. That is the patch material categories for CDH, estimation of recurrences in patch materials, analysis of patch materials, and the mechanism of integration. There are much more topics, as you can see later on, but I don't think it will be in the context of this webinar. Now, choosing the right patch for CDH is very important, especially when you go to different places and they say we have this patch. So it's like choosing a tire for for whatever you're using. We have different forms of tires. A lot of people are not aware of the different types of patches and what they're to be used for. So what is required is to use a specific patch for the purpose that you're trying to do. So we need to get something which is more specific for CDH. Now, when you look at patches used over the last 30 years, please bear in mind, the last 30 years were when people started using biomaterials. These were found to be uh taken off from a systematic review. Uh, we found that there were 13 patches and composites used in repairs of CDH. Uh, these are human studies. So, I divided them into 4 categories. One is synthetic non-absorbable materials, which you can see the names below. Very common is the Gorote in this group, uh, dcrons, Teflon, Marlex, and elastic. Then you have natural absorbable materials. which you can recognize the group below. So this is uh dura Permacol, Alloderm. Then you have composite materials. These are a mixture of one or two. so this is uh CCVM collagen-coated vicry mesh, and you have composites of non-absorbables, which are compositions or, um, uh, which take one or two of these materials and put them together. Now, we need to know what these materials are, although the 13 materials have been used in uh human uh repairs. What these materials do and why they are working and they're not working. I looked at the recurrence in patch categories. When you look at those four different categories that I showed you, we see that there is recurrence from 26 to 30%. So no matter what material you take, one third is bound to fail or has shown failure in the reported series. I'm not going to refer to this material right now, but this material is highly degradable, and it fell off anyway. So when you see the other three categories, it's between 26 to 30%, the failure rate in patch repairs. Now, we look into the characteristics of these materials, so you get an idea of what has been used and what works and what does not work. Now, the most important, I've posted on the left hand side on the top, what type of material it is, if it is absorbable or non-absorbable, and the recurrence rate. When you see Gorotex and Teflon, people confuse that in the reporting. Teflon is generic PTFE while Gorotex is expanded PTFE. So there are initial reports that mentioned that we use Teflon. I'm not very sure that if it was Teflon itself or Gorotex that was used in these uh uh patients. The manufacturing process of Corotex and Teflon are completely different. So this is not like this is also the same PTFE. One is expanded. So as you can see, the expanded PTFE is made by an extrusion process, while generic PTFE is a cellulose binder and volatilization. I will concentrate more on Gorotex because that is the material that we use in present-day repairs. Now, looking at Gorotex, it's a synthetic material. It is non-absorbable. It has a recurrence rate of 28%. Now, what is very important in Gorotex is the porosity, that is the distance between the two layers of the Goro-Tex, and this is defined as the internodal distance and is around 30 micrometers in expanded PTFE or Gorotex. Now, why is that important? As you can see, That micropore meshes less than 10 micrometers, they exhibit higher rejection rate because the scar tissue rapidly bridges these holes which you can see on the side over here, and this results in minimal integration. So you do not use a micro porous mesh. You use something which is like the present Corotex, 30 micrometers, which allows integration of tissues and no blockage by scars. So 30 micrometers is very important. It facilitates microphages, fibroblasts, and collagen entry and integration of this material. We move to the next material that is Dacron. This is from the company DuPont, synthetic material. It's not absorbable and has a recurrence rate of 5.9%. I think this is low because there are not too many series which have been reporting on Dacron. This material is also similar to the material which you know from your clothing, which is polyester. The graft is chemically harmless and easily tolerated by the body, and when used in blood vessels, especially, the body eventually grows a new lining in the graft, and this mimics a new blood vessel lining. Now there are advantages and disadvantages of polyester. One is rapid fibroblastic infiltration, better fixation to tissue, and less mesh shrinkage when you compare this to polypropylene mesh, which I will mention as the next type of tissue. But there are disadvantages also higher rates of infection. Adhesion to viscera, if placed in the intraabdominal position, and there's a loss of strength over time. But of course, all these studies are small because the number of centers that have used Decaron are quite less. Now, polypropylene mesh is, uh, as you can see here, a Marlix mesh. It's a synthetic material. It's non-absorbable. It has a recurrence rate of 22%. Now, it offers the benefits of high tensile strength and strong mechanical reinforcement. It allows rapid ingrowth of connective tissue. However, please bear in mind this is very poor quality of collagen that grows inside these. The drawbacks uh for our in the foreign body reaction because of reduced compliance. There's increased pains if you use heavyweight meshes. So the, uh, uh incentive would be to use lightweight meshes, and adhesion formation is done if these meshes are in contact with the viscera. So if you're using one of these meshes, make sure that it's on the thoracic side and you have some other kind of composite which is facing the abdominal side. Elastic unfortunately has also appeared in the list. It's a synthetic non-absorbable material, and I'm not really sure why it was used. It has a high rate of recurrence. It's a relatively inert material and offers minimal tissue integration. It's not envisaged for implantation, and I don't think there are too many people who use silastic itself as a diaphragmatic replacement. But, however, in the literature has been reported with CDH repairs. Another material, now we move to the degradable type of materials. This is a natural material that is sergesis. It's absorbable. It has a recurrent rate as high as 37%. Now, this is from porcines small intestinal submucosa, which we call SIS and during the healing process, SIS is replaced by the body's own tissue, leaving behind a fibrous repair. Now, we have the biggest problem with surgis. Nobody has really reported it. They're using 4 layered or 8 layered surgesis. They come in these two variants. Now it's easy to suture the 4 layered variant because it's much easier on the sutures, and when you try to stitch it on the wall, 88 layered are quite thick. They're almost like suturing leather. It's quite difficult to do it. So the recurrence cannot be really calculated because there's inconsistency in reporting of whether 4 or 8 layered surgesis has been used. Puttoplas dura has been used. Also, natural material absorbable recurrence 175.5%. I think there was a lack of reporting. I think the recurrence is much, much higher than 17.5%. Only the reporting in the series early in the seventies and early eighties, after that, there has been no reporting on this material for CDH use. Something which has found a lot of fashion is porcine dermal collagen, which you will know as permol, natural material, which is absorbable. Again, a recurrence rate of 11%. Now what happens is this material is prepared by removing all DNA RNA so that you do not damage the 3D collagen matrix. But what you see in this collagen matrix, this is the image of the permol from our lab, which shows how dense this entire collagen is. There's another problem with that, that this material is cross-linked with non-calcifying uh uh HMDI which is once you have a cross-linked material, it's so thick, it does not allow tissue integration, it does not allow cells to penetrate into that much easily. So cross-linking of Permacol allows lower cellular infiltration, lesser extracellular matrix deposition, and decreased neovascularization, and that's the reason for the main failure of Permacol. The cross-linking offers very little advantages after 3 months of implantation, scarce reorganization of the host connective tissue, insignificant infiltration of IL-6 positive macrophages, and minimal blood vessel ingrowth. Another interesting material also used in CDH repairs, it's natural, absorbable, and it has a recurrence of 40%. This is called Alloderm, and you must have all heard about it. It is derived from human cadaveric dermis, which contains and retains the properties of collagen 4, which actually sounds very interesting, but this material has had problems. It allows for tissue regeneration by supporting revascularization and cell repopulation, and these lead to an increased resistance to infection at the surgical sites, great for using on the skin. But we've had problems with Alloderm, and most of us in Europe have not used it, and that is because of the following reasons. There are regulatory restrictions on human products within the European Union, and the cost of Alloderm is so high that we prefer or favor the alternative products which I've mentioned to you before. One more important thing that we missed out was the current Alloderms or the ADMs are offered as aseptic. They are not sterile. That means this has led to the debate of post-surgical infections. So until now, all the alloderms that have been used, uh, that have been aseptic, but they're not sterile, uh sent to you uh for human use. So now there's a South Korean company called Megaderm which offers a sterile ADM, and this is processed with an electron beam achieving 10 to -6 sterility levels. So this is the first product which has actually is used as a sterile instead of an aseptic one as offered by Alloderm. I'll just briefly touch on collagen coated vicryl meshes. These are, as you can see, a vicral mesh over here with collagen on top of it. It's absorbable, 100% recurrence. And the reason for that is it is difficult to identify the host collagen two weeks after implantation. And the biggest problem is the implant is completely replaced by fibrous tissue, and the intensile strength of this implant and scar tissue is the weakest in 8 weeks. You're bound to have it rupture and fail. Has been used in humans, but 100% recurrence has been seen with that. So I'll just summarize the issues with the patch, patches for CDH. Integration with bodies is poorly understood in synthetic non-absorbable patches. With the growth of the newborn to adulthood, we are not very sure if these patches expand or tear. We don't have this answer until now. Chest wall deformity association in patches is poorly understood. You have a patch which is on this side, the chest expands. What happens to the chest? Does it stay restrictive or the patch rips off at that point? Vascularization in patch is also poorly understood. When you put a patch, vascularization comes only from the periphery. Unlike a patch which you put on the abdominal wall or hernia repairs, it's in contact with tissue throughout, so vascularization is not an issue over there. But big problem in diaphragmatic hernia because you have only the circumferential vascularization potential. I'll just touch a few slides on mechanism of patch integration, and this has to be understood how this works. The biomaterial implantation is followed by a complex cascade of events that trigger the healing process. This involves destruction or lysis, inclusion or tolerance, and rejection, which is T cell mediated. And what happens is the inflammation is a biological reaction to the biomaterials. As you can see, they are in 4 different phases. The first phase is an acute phase of inflammation. The 2nd phase is a chronic inflammation. The 3rd phase, you get a immune response or a foreign body reaction, and the 4th 1 is a scar tissue formation. Now, interestingly, it is also depend on the size of the tissue reaction. It's not that if you put a small patch, you'll have the same reaction as the large one. Cell density and the fibroblastic activity. Now, when you see the fibroblastic activity, it peaks in the 1st 2 weeks after patch implantation. This is what your body starts fighting against, or the neonate body starts fighting against the implant. What happens is this process lasts for around 12 weeks, and the final strength is 70 to 80% of the native tissue after 12 weeks. The problem comes in over-aggressive integration. This leads to biomaterial rejection. So the body tries to integrate it more and more. There's more and more secretion, fibroblastic activity, and that's where you get rejection of these materials. So these are some of the experimental studies that we did. We used all these patches in the ovine model integrated into the omentum as well as into defects, and we tried all the 13 materials. Just to give you an idea, this is a cross-linked material. This is porcine dermal collagen, does not at all integrate even 12. Weeks after implantation, versus other materials which you can see have better integration properties. So, it is very important to understand these integration properties, especially when you're choosing natural materials, and uh especially uh that they should not be cross-linked, or if they are cross-linked, that there is a reason for that cross-linking. So, just as you see, non-cross-linked dense collagen over here, it integrates cross-linked dense collagen over here, not at all, no integration. Non-cross-linked porous. There is an integration on the side, and there's a dual layered collagen, non-cross-linked compressed collagen, complete integration on that. So there's a lot of research going on in trying to devise the optimal biomaterials, which unfortunately has not been at the present moment possible with the patch repairs. So I've summarized the talk in these 4 or 5 sentences. There is no unanimity on the optimal biomaterials for patch repairs and congenital diaphragmatic hernia. Contemporary biomaterials for CDH are associated with recurrences, all of them. Biomechanics and integration insights are necessary to understand patch repairs. The variations in reporting are also dependent on the size of the defect. People report, I did a patch repair. Did you use a small patch? Was it for a type B or type C or? Or did you use a complete uh repair, whether you used it with tension or without tension, that is very difficult to find out in the literature. And no patch to date has been specifically produced for diaphragmatic hernia replacement. Thank you very much. I'll end my talk over here. Thank you very much, Amelia, for this very nice talk. Um, introduce to you, uh, Jose Luis Pero who actually does not need, uh, much introduction. Uh, Jose Luis is, uh, from Spain, actually from Catalonia, from Barcelona. Uh, but in about 7 or 8 years ago, he, correct me if I'm wrong, he moved to the United States, and since then he's been, uh, at Cincinnati Children's Hospital Medical Center. He's a professor of surgery at the University of Cincinnati. Medical college, um, he's a fetal neonatal pediatric surgeon and he takes pride of being one of the first ones who actually pioneered one of the very first fetal surgery programs in Europe in 2002. Uh, he's one of the few, uh, pediatric surgeons, in fact, and fetal surgeons that do fetal. Uh, but also one of the first ones, uh, uh, a pioneer, and in fact he's the, uh, director of the endoscopic, uh, fetal Center in Cincinnati, um, and, uh, has a specific interest, uh, in, uh, uh, congenital anomalies including congenital diaphragmatic hernia. He's published, uh, uh, several papers on CDH and most recently also uh as Jose Luis has a lab, a very active lab in Cincinnati. He's also published a paper recently on a new patch material, uh, that could be useful, especially for people that do, uh, thoracoscopic CDH repair. Uh, so, Jose Luis, uh, uh, thanks for, uh, we, we all know that you're very busy, you have a very, very busy, uh, agenda, and in North America, now it's, uh, uh, 10:00 a.m., so it's, uh, it's morning, so thanks for joining us and for sharing with us, uh, uh, your view on, uh, pash materials for CDH. OK. Thank you, Augusto. Thank you, Martin, and a pleasure to be with Amulia. So, uh, I would like to share, uh, my experience in CDH uh talking about uh patches and flaps. So basically, uh, What I will focus my talk is in the uh muscular, uh, abdominal flap. And first of all, what I need to say is that uh we need to talk about a little introduction about what CDH is. So, usually, when we talk about CDH we talk about the bottali uh hernia and you know, there are different sizes, so they can be very small to very large. Actually, sometimes it's a complete agenesis of the diaphragm, so, there are some publications that they say that is an incidence around 30% that you don't find any muscle. And basically, the classification we use to uh define the defect is, uh, is this one of the congenital dramatical hernia study group in A, B, C, and D when C and D are really large defects. So, that correlates with the content in the chest and also with the severity, all right? So we can find uh defects that correlates with a mild or moderate hernia and mostly with the severe category, usually we have uh a large hernia with the liver up and that's why the liver is allowed, the left side of the liver is allowed to go up to the chest because the defect is really large. So, perinatally, we know very well that uh liver, uh, the liver herniation to the chest is an indicator of poor prognosis. So, that's a very important detail. And then we need to be ready for this severe category to offer all our neonatology, uh, tools including uh high frequency ECMO, etc. and also offering different strategies we have like exit to ECMO. Right now, we are moving more to C-section with ECMO standby, so we have the ECMO Machine Prime in the OR so we can actually cannulate the baby in the few uh uh minutes before uh after birth and, and we have pretty good results with that. But anyway, uh, currently we are performing the fetal, the tracholocclusion in utero in this severe category to try to improve the outcomes. And basically, that occlusion of the trachea will help the, the lung to grow in utero and potentially increase the survival. That's OK, but still, this treatment are not changing the defect. So, still we will uh have a thematic defect that remains the same and usually large that should be repaired. So this is more or less our experience in Cincinnati in the Fidel Center. We did more than 300 evaluation in the last years and this is our survival as this chart so we have almost 100% survival in the uh in The small defects, but still we have close to 50% survival in the large defect that correlates usually with the severity. So in the severe category of CDH we have 50% survival, but still these babies that survive will need a repair. Now, with the future, we have even better results and as I said, these defects, they are large and they need to be repaired. So, what is our policy for repairs? So, usually, we are considering surgery not as an emergency. You, we, we usually do the surgery in the best cases between the 3rd and the 5 days of uh postnatally, but in many other cases that are unstable, we wait for weeks until the baby is completely stable and we have uh uh non-suprasystemic pulmonary hypertension. So then, of course, in the small defects, we will look for sacks, we will look for defect and in most of the cases, we will do a primary repair, OK? That uh is pretty straightforward and usually have good results. Of course, then after that, we need to uh rehouse all the viscera in the belly and close the abdominal cavity that sometimes it's not possible and we temporarily, we need to put a piece of patch uh for uh a little more room in the, in the belly, but The problem is when we need to face large defects. So, at that point, it's very rarely almost impossible, we can do a primary repair and then we need to choose between patch and muscle flap. So, we still, we are using patches. We are not against patches, absolutely, and basically, what, there are many in the, in the market as Doctoro uh Sacena showed you and, and we are right now using the dual mesh from Voritetex for these repairs. And obviously, we try to do a floppy patch to avoid recurrences, but it's still it's almost impossible to avoid completely rec uh recurrences. Also, we use patches for tranchoscopic approach. As you can see here, we still use the same uh uh Coretex 12 mesh. And also, as Doctor uh Sanny recommended, we recently with Doctor Abbeello in Colombia, we designed a new uh patch, a new uh system of the patch to uh be more simple and archoscopic application uh using uh this system of uh of folded, uh, periphery and also a stitch for stabilization. So this is simulation so we can push back to the To the abdomen, all the viscera, so then we can pass this system, this patch that once it's in the belly, we can pull and then it's retained by the uh elastic ring, so we can actually do the suture from the muscle of the ribs to this, uh, these folds in the, in the, in the patch that makes more safe to avoid any injury in the, in the bowel and complete the, the closure. So Uh herniation in patches is well-known and there is a different number. So, they're from 50%, 41%, that is very common to see that, uh, to the 25% in other groups and uh the less uh uh frequent is in 5% or 5.4% in these two series, but still recurrences. So, that's why many surgeons started to try to use muscle flaps, uh, from, from the abdomen. And the, one of the flaps is possible is to use the Latissimus dorsi that I use it in, in two cases, uh, one for uh operator recurrence and that is a good, a good option, OK? You go in between the ribs and it's still a good option, but, uh, but it's not very common. The more common is the split abdominal wall muscle flap, OK? That you can see here that you have a donor area in between the, the last rib and the incision, so, you need to go down in the incision. So, otherwise, you have not enough muscle, uh, for, for flap, uh, for the flap. So, basically, the technique is uh designed for using the uh transverse abdominance muscle, but many times in these babies, muscle prematures are very thin, so we prefer to include the internal oblique muscle, muscle and then flap this uh like a door, OK, over the 12th rib, OK, down inside the, the, the defect. So, basically, schematically, we usually don't use the, the rectum. We can use part of the fascia, but mostly we use the, these muscles that, uh, that can be flapped and flipped to the, to the rib. to cover completely the defects. So, the advantages we, uh, we advocate is they are vascularized and innervated autologous tissue is the, uh, it's a, it's a muscle that will grow with the patient constantly and we don't have the restriction of the patch. So, as I said before, we need to do a lower incision. So, usually I go a little bit up to the, to the belly button and do a complete transverse incision. So that allows a very good uh donor uh muscle in the area over the, the incision. You can see here how we can separate very easily the three layers of the abdominal wall and then, uh, flip uh down the, the one of the two layers, internal layers in this, in this case. So, at the end, we can attach to the other reminder muscle or just around the ribs, OK? This is another example how we do the split of the layers. It's really very easy, very fast. And then we go down. This is the external oblicle that will stay for recover the, uh for maintaining the, the, the, the closure of the abdominal wall, but here, usually we use pledgets, OK, that reinforce the closure of this muscle flap in the big defect. So, at the end of the procedure, we have this incision and the only thing that we can find sometimes some uh weak area over the incision between the ribs that remains for some months, but in the long term, that usually recovers. So, this is what we look in the controls. So, after that, sometimes can be a little protrusion here in this area, but usually in the long term disappears and also in the X-ray, you will see that diaphragm is a very low lying, OK? Usually, it's the 12th rib and then it's a very low uh barrier in the, in the, in the chest, uh, in the X-ray that is differently from the other contralateral diaphragm. So, talking about results, so I started to do this technique in, when I was in Barcelona. So, we completed 10 cases uh uh that basically on, on 100 cases we had, uh, it's a 10% of the cases and uh we basically uh did in large defects, of course, many of these babies had prenatal tract occlusion before. And the, some of them, they have this bulge that resolved almost in every patient, only one required anatomminoplasty in the future and then we have two recurrences, one very late at 6 years old and other after 3 months, and there were chest wall uh notices in half of the patients that probably are inherent to the hernia. So the follow-up was between 2 years and 13 years. So, this is the list of the patients we did in Barcelona. You see that there are many different patients and many of them had the fetal for treatment. And uh this is the uh results. OK. So, Many few persisted with the abdominal bulge, OK. They're all alive and two recurrences here. And one at 6 years and another at 2 months. So, the conclusion is that uh in this work that the abdominal uh uh wall muscle flap technique is a valid alternative for repairing large CDH besides the patches. So, I learned this technique, uh, reading from uh the paper from Dr. Gloria Polizzo that many years ago reported 15 cases, OK? And, uh, she stressed the advantages of this technique, as I say, it's more accurate reconstruction of the diaphragm dome, a good tolerance, a result of autologous material and less risk of recurrence of or infection. So, disadvantages are obviously the abdominal herniation at the side of the muscle flap that, that sometimes requires some surgical treatment as I commented before. But actually, I learned the technique really from uh Eric Skefi that he was in Philadelphia in, in this year and we uh we commented that. So, from him, he had a very good report in 2003, this, the, the defining very well the technique, OK? And uh all the, all the steps of the technique and we in successfully eight cases that he performed. and publish it and then later in the, in the 2012, he published it even more. So, actually, 23 cases with muscle flap and then it's not only a good technique for them, it's also they've demonstrate that they have significantly fewer recurrences than with patches, at least in their hands. So, this is a question. Is, is, is less recurrences or not? So, there's another paper from, uh, actually from Toronto that they compare 19 cases with muscle flap versus 32 with patch and they found they're half providing similar short-term and long-term outcomes. So, not a big difference between the two techniques. Finally, a group in, in, in Japan, they also uh refer that it's an effective technique for repairing large defects and also they incorporate a piece of Marlex in the donor part of the abdominal uh area to reinforce that, uh, that weak area. And finally, our, our, uh, caustics, so our series in Cincinnati. So, we recently published this paper where we retrospectively review for the uh for 12 years, a total of 171 patients from, uh from our series and 131 were, were long-term survivors or having adequate follow-up because some of them were lost in the, in, in, in the follow-up. So, of these cases, 70%, OK, 93% cases required a technique different than primary repair. So, actually, we collected 34 cases with a patch. We use Gore-Tex Omesh and 57 cases with abdominal uh muscle flap and the follow-up uh is an overall of 4 years between 1 and 12 years. So, this is the chart of, of the cases. As you can see, we started with 171, but finally, with open repair, we have almost 120. It's 90, 90% of the cases and 12 cases minimally invasive repair that was excluded initially from this. So, Uh, from the primary repair, we have only one recurrence, still, it's not perfect. Patch repairs, we have three recurrences that represents an 8.8% and in the flap repair, we have only 2 recurrences that corresponds at 3.5%. There was one rare recurrence in the group of the patches. So if we analyze the two groups, patch and Flap, we see that uh both are very uh Very similar in, in demographics, OK. Uh, all deliberate 37 ways uh as a, as an overall and all have similar uh prenatal diagnosis. And in terms of the ernia, we can see that the only thing we have more left-sided earns, 86% uh in the, in the flap, probably because when we have the lever up in the right side, we are more confident with patches than flaps, but still it's possible to do right CDH with the flap. And the other, uh, categories like this defect size, etc. or the severity of the earnias are very similar in the two populations without significant differences. Finally, uh, The only thing that is different in the two groups is the appendectomy that is more frequent in the flap surgery, probably because the surgeon preferences, but otherwise, all the data about time of the surgery, uh, age of the operation, everything is very, very similar. So, even the dollar loss is, is really similar. So, patients on ECMO, sorry, Patients on ECMO and uh cannulation, length of stay, everything is very, very similar. The only thing that we need to commend more especially is this. So, the earning recurrence, as I said before, is 8% versus 3%, OK? That is not statistically significant, uh, so, no difference. Even if we add the case of a recurrence with a patch in the, uh, in the horacoscopic case, we will increase that to 4 cases. It's an 11% recurrence, but still not becomes statistically significant. This is the uh cases, the 3 cases of the patch and the 2 cases of the abdominal flap we have described. So, it's only to say that this one of the muscle flap again, very late in, in date. So, it was an, uh, a medial um uh failure, but most of the cases are posterior lateral uh uh detachment. So, in conclusion, uh, using a flaps, so, this is to compares patch repair to muscle flap again, and both groups were equally matched with regard to patient sta uh stability, size of the defects and clinical manifestations and both approaches, therefore, proved to be safe and feasible. So, in our view, open CDH repair with the patch or the muscle flap, even is less for the flap, there is no significant difference in recurrescence rates, so, between each, uh each method. So, both approaches, therefore, are considered durable options for CD repairs in which the defect is too large to be repaired primarily. So, there was no significant difference also in the overall survival. So, finally, our data suggests that that's still abdominal muscular flap repair is a valid alternative technique. Ian, for to, to, to finalize the talk, the other question is that works also on ECMO. We can use this technique on ECMO. So, Obviously, we do many repairs on ECMO and obviously, you need to be ready and prepared for the MRI. So, you need to do a very meticulous visual handling, uh, very tight control of the anticoagulation and use medication like Amicar, decrease the Eparin and discontinued the AC3 to do these surgeries, but it still is possible. So, the question is what's better for CDH to repair on ECMU patch or flap? Because usually are huge and large defects. So, it's the muscle flap feasible and safe. So that's the, the idea. So, I need to say that when you separate the layers of the muscle, it's a plane that is almost a vascular. It's very easy and very straightforward. So, you don't lose time and you don't lose blood on that. So, the, we did this uh publication uh recently comparing the bleeding complications and the bleeding requirements for on ECMO patch versus flap repair of CDH and then we uh complete 29 patients, OK? 13 cases with patch, 16 with flap repair. All were C and D defects, of course. And then, Uh, most of the cases were left-sided defects and we don't find any difference in gestational age of delivery or the timing of repair. So, in general, both have similar at moderation, and more uh repair to the cannulation uh and including we have an estimated intraoperative blood loss very equivalent in both groups. All right. Also, the survival in both groups was 55% with these repairs on ECMO. So, in conclusion, we can say that there's no difference between the two techniques on ECMO and the abdominal muscular flap repair is still a valid alternative technique also on ECMO. And that's it. Thank you very much for your attention. I'm happy to discuss and answer any question. Thank you very much, Jose. This was, uh, great. Uh, you can, uh, stop sharing your screen. That's, uh, that's great. We got, uh, a lot of questions, uh, for both of you. Uh, can I just start with one which has got not, not much to do with, uh, the patch repair that we talked about, but there's a question from, uh, Stefan Polka about, uh, the total, total trial. So because you're doing, uh, fetal. Uh, do you have any, um, can you anticipate any results of the total trial that, uh, Jan depressed? I know that, uh, the paper has been submitted and they, but, but we haven't heard officially anything yet. Well, unfortunately we need to wait for the publication, so they are analyzing all the data. So what's supposed to be published at the moderate category that was recruited before, so was expected for this past spring but still not published it and the severe category was, uh, uh, stopped the recruitment. Hopefully by efficacy, but we still don't know. And uh they are, they are working on the publications and, and it's part of the, of the, the treat of the total trial that it will be not anticipated results. So, Everybody's waiting. We don't know that was posted twice and that's why I wanted just to clear the desk. You answered that and then we can talk about the patches. Sounds good. There's one question from Bangladesh from uh Mitul asking, is it possible to have an idea of the size of the defect pre-op, so um that you can counsel the parents whether you use a patch or not? What are your criteria to estimate whether it's a big defect or rather small one? Uh, Martin, it's in present day and age, it is possible to estimate the size of the defect, more or less. Uh, there are a couple of parameters, as Jose Luis has mentioned, if you have the liver up, that is one sign. And even if you do not have these facilities of fetal MRIs, one very important score that we use for a large defect is when you, when the baby is born and you pass an NG tube, and if it curls up into the chest, that means you have the stomach in the chest. These are two indicators which definitely are on the side of a large defect. And, you know, as well as I do, most of us who try to go in thoracoscopic, sometimes you then find out that the defect is larger and then you might need a patch in that. But two indicators, liver up and uh the stomach, the NG tube curling up into the chest, it's going to be a large defect. Mm. Yeah, I totally agree. So you can prenatally, if you have good ultrasound and MRI, do an estimation because that signs of the liver up or the stomach, um, behind the, the, the, the, the heart or other, other signs like that, but basically correlates with the severity. You have a very good case of baby, you can think that probably it's a small effect. On the contrary, you have a baby, you're dealing with the baby, pulmonary hypertension, maybe eCO, most likely will be a large defect COD. Mm and um questions from Judy. I'm sorry um um Amelia, as you mentioned thoracoscopy, what is your limit in Doing a patch repair thoracoscopically, is it a type B, C, or even D defect? Well, you know, C still comes in the larger category, and you will still need a good size incision to bring in your patch material. And we're just uh evaluating, and as you've also seen, data is having a higher recurrence when you use thoracoscopic repair for patches. So, uh, my approach now is if you have a patch size of a defect size of, let's say B, you could go in for a thoracoscopic still repair of a patch. If it's a C or D, then I would rather go in for a proper patch repair, and I prefer these, uh, dome-shaped patches to give a lot of, uh, flexibility, which causes a A lot of anxiety in your intensive care, uh, people who take care of the babies because it's like everything is still up because you've used a huge dome, but you just have to calm them. It's not a hernia, it's a huge dome. It will take time, which brings us again, back to the question of, uh, you know, how the patches stretch over a period of time and what happens to them in a couple of years. I totally agree. I think that it's uh how you fashion it rather than uh necessarily what kind of material, uh, you use. Um, there's a question from Judith Linter, um, are there any differences? I think that, uh, Jose Luis, you, you alluded to when you were talking about the, the, the flap, but in general for you and for Amulia, are there any different results, uh, with the patch or with the flap, uh, with regards to the laterality of the defect, if it's, uh, right or left? Yes, I mentioned, so. Usually the, in the right CDH for, by definition, you have the liver up, sometimes very up. And it's hard to push down the liver and to allow the belly to contain that big mass. So sometimes we prefer to, to put a patch, OK, that you can attach very well because the muscle flap, obviously, you need to, to take the muscle and go down to the ribs. So sometimes you also have a very low laying of the, of the, of the Neo diaphragm, so you are limiting the space in the belly. So I think that, uh, as, uh as Mulia said, so you can do a good dome, so you can allow the liver to be content. So probably for, for very high lever up, right CDHS patch can work much better. It's still, you can do the flap, of course, but uh it's a trend to do more in left sides. Yeah. Yeah, I agree with him. On the right side on the liver, I've only had one approach abdominally. Then after that, I prefer the thoracic approach to put in the patch from the top, push down the liver slowly on that, try to put my stitches around it. Um, uh, Augusta, just one point which I would like to make here. In the right side, if you have a recurrence, that's a little bit tricky. Because what happens is if you use a patch over there, and I'm, I'm fortunately not in the position to give you this answer because I've only results from experimental studies, if you use a Gorotex on the right side, it completely sticks to the liver parenchyma, completely on the top of the surface. If you have a recurrence and if you try to detach that, you're going to shave off the liver and have a huge bleeding. In that case, it's better to put a second patch on the top, push this one even below, and suture it, but I do not have the same results from the other biomaterials. But with Gorotex, it sticks very strongly on the liver. Don't detach it. Like if you say I want to remove this and put a new material, just put a second one on top. That's a great point. That's a really great point. I agree. There's one more question from Polona student, Paul Letic asking on the perioperative treatment and management. How do you speed up the process of making these? Uh, in terms of forego development, position of the stomach, is there a problem with volvulus of the stomach and so on? So what is your perioperative management to? Get to full feeds as soon as possible. Uh, difficult question to, then I can go after that. Yeah, so, so many of these babies with large defects have obviously, uh, totally mal position of the, of the stomach. Many times in utero, they are like twisted, like I ovulated, so are distended, OK. So there are, there are many difficulties for feeding, for tolerate feeding these babies. So, so they will need probably many, many months with uh. With, uh, uh, NG tubes and we, we do uh uh gastrostomies in these babies many times because they have no tolerance and in a portion of them, we need to do a, a fund duplication for, for reflux. So, sometimes I was wondering in this case if we can do in the first surgery, the, the fund duplication, right? So, I don't know if it will be helpful or not. Sometimes we spend some time uh doing lots, uh, removing lots bands and uh trying to put the stomach in a better position possible, but still it's a, it's a good question. So, but it's clear that these babies will need uh a lot of uh uh effort for feedings and many times gastrostomies. Uh, there are a couple of things which are very tricky right now, and especially in the thoracoscopic age. When you put down the gut and all, you do not know if there is a malrotation or not. So this is something which we cannot answer, especially in the thoracoscopic age. The second thing which also brings to a lot of attention is As, as you have noticed, there are publications on delayed abdominal closure. You've put everything into the abdomen and you find that the tension is so much that you have to make an abdominal incision to release this, probably with a silo or something, so that you can then, you know, accommodate this gut or whatever you push down inside. And then there is also reporting on abdominal compartment syndrome. So you may not have any of these, but you might have subtle parts of, uh, you know, abdomen compartment that might delay your child from taking the nutrition. Because that was the question that you've asked. So yes, there are straightforward cases in which, you know, you put down everything and they start the nutrition. There are cases in which they might have this some form of an abdomen compartment. I'm just saying some form so that, you know, things that that there might be a degree of volvulus, a degree of volvulus because of the malrotation which Has to settle down. So, what was very interesting is none of us do sequential upper GI imaging to see whether these children are having a mal rotation or not. And the second thing is we are, uh, we've just now come out with a letter, which will be published probably next month, is, is it important in these children, even if they have a malrotation to do anything? Because malrotation surgery, as you know, is also with complications of redo surgery. So, in case of CDH this is one question which we still have not sequentially answered. So do you always look for la bands when you do an abdominal procedure for a CDH? I do not. I do not. My approach is not to look for it. Jose. Not in general, but lastly, we are taking a look on the, on the, on the lads. So we remove the appendix and we take the, the lads, but obviously virachoscopy is not possible. So, I think, I, I don't know if it's really essential to do it, but just in case, in some cases we do it. Yeah, there are people who say I was not trained to do a lot. I have to say the same. I think most of these patients are non-rotated, and not necessarily non rotated, so they have already the rotation anomaly that you would give them with a LAS procedure. There's a lot of questions that are coming on, you know, the CDH. Uh, it's so controversial, so many controversial aspects, and so one was what do you do if you find a sac at the level of the diaphragm? Do you resect it, and, uh, and regardless of what, what you do with the sack, what do you do again? uh, patch, you modify your, uh, uh, choice for the patch if there is a need for a patch. Um, in terms of uh the type of patch or uh uh patch versus uh muscle flap. Well, um, regarding the pleuroperitoneal membrane, in when you even do a thoracoscopic, so I try to score the edges of the, uh, of the rim so that it adapts better or you have some kind of tissue which can fuse together. So, yes, I prefer to score it a little bit. To remove a physical membrane, I do not do that, but I just score the edges while I try to readapt to that case. So that is my approach in case uh uh regarding that part. And uh the patch part again, like I said, I went extensively through the patches, and I can only agree with Jose Luis, this dual Gorotex patch is the best, which is on one side, it has a polypropylene, the other side is Gorotex. This has definitely shown lower recurrences than even Gorotech. So if somebody's planning, that will be one of the ideal things. Uh, with, with regards to, uh, something which you've shown very nicely, Jose Luis, is that if you make the wrong incision on the upper part, just below the rib, then you're gone, then the patch is not available for you. So what uh centers who like to do this thing, it's better to put in a scope first. If you see it's a large defect, then make sure that the incision goes lower so that you can accommodate the muscle flap. There's nothing wrong in doing that, but if you make the higher incision, then the muscle patch, unfortunately, according to me, it's not possible. Yeah, you are right. You're right. We, we are systematically doing lower incision. So we have the option of the flap all the time. Sometimes it's a primary repair, you don't need it. So just you close. And about the sac, I usually resect the sac. Uh, I, I had many years ago when I was a trainee, uh, a case that uh a sac was not identified or was left there and created like a cyst, OK, like a big ball, uh, inside the chest. So I recommend to, to remove the, the, the, the sac just to take a look on the, on the, on the lung and see if there is no clearly seen. So usually it's a thin layer uh that you can usually with analys or put a stitch and pull that sac and then do it so you can see very well where the sac is becoming muscle so you can cut all around and usually you can still do a primary repair. Quick question, uh, as you were, uh, referring to the level of the incision. The, the group of Mannheim who are doing 70 to 80 cases a year, they advocate a vertical incision in the midline actually because they argue that the, uh, abdominal wall muscles are needed for respiration also. And I changed my protocol to a vertical incision too, which is really, really nice. Is that, would that be an option for you? Have you tried that or? Not, not if you are planning to use a muscle flap. Uh, I don't know if from a midline incision you can still Detach the inner layers of the muscle will be more challenging. So, That's why we don't do that. Sometimes you need in a very large defect, you can extend like an L shape a little bit, but, uh, usually we do a transverse. OK Then there's another question, what happens to the patch when the child is growing? Amulia mentioned we all don't know, but uh Dominic Smircek is asking, did you encounter recurrences after 4 to 5 years when the child is growing? Um, Martin, I think most of the recurrences that we have seen are very early recurrences, which I call these happen within the 1st 6 weeks, or you have the little, what I call late recurrences that happen within the 6 months that these children come back to you. I can't recollect in the last 25 years that somebody coming at the age of 4 or 5, you know, with any patch disruptions. Of course, don't ask me what happened to these patches. The size which we put was so small and, you know, the chest has definitely Uh, increased in size. But yes, there has been one very, very nice report. I mean, now there are more of them, with chest wall deformities and this constriction which is happening there. But this is a, it's a million dollar question, what happens to these patches, especially in type CD defects, uh, you know, in, in a type B defect, uh, it's very easy. It's one part, it just integrates, the rest of the muscle and the tendon grows. But CD, I have no answer for this question. Now, this is, um, there's a, uh, a post from uh Sanne Botan from, uh, from the Netherlands, from Nieme and uh telling us that actually they just published an article on a malrotation in CDH and the subsequent risks on, uh, general pediatric surgery October 2020. So this is just to show that we're not just here to discuss and to share our, well we know our knowledge, but actually we learn a lot from all the other colleagues. Um, a question that's been posted by, twice, in fact, by Stefan Poca who says we need to look at how, uh, patients, uh, get access to our therapy. So for, um, um, Jose Luis, uh, do you have data from prenatally diagnosed about aborted, uh, um, CDH babies after consultation, uh, compared to the ones that, um, uh, have been delivered, delivered. Do, do you have any data from uh your uh OBGYN? So what's the question actually comparing the the ones that have been diagnosed prenatally and then uh get uh aborted terminated uh compared to the ones instead that that get delivered because you're doing a lot of uh fetal surgery so maybe you have uh more access to data. Yeah, so, so, yeah, actually detection is very high both in Europe and USA so we have good referrals and and on time. And I need to say that uh probably in USA the rate of interruption of pregnancy because the CDH is very, very low. Usually, uh, parents uh choose for aggressive treatment, including ECMO postnatally or if it's a very, very bad case, in some cases, they decide for comfort care. So like not make uh very aggressive things and they only, they hold the baby, do some memories, and that's it. Uh, in Europe, there are more, uh, uh, probably rates of, uh, families that decides to do interruption of pregnancy, but I think, uh, that was more in the past years. Now with the prenatal therapies, at least when I was in Barcelona, probably in other places, the families are looking for options and looking for fetal, looking for other things besides uh going for abortion. So the, um, Stephanie is asking about the percentage. I can tell you that I know here in Toronto there's a couple of more or less 1 to 2 CDH babies that are terminated after the diagnosis. Parents want to interrupt the pregnancy, and we see around 30 CDH babies a year. I don't know what's the, what's your rate in Cincinnati? Pretty similar, pretty similar, the same. Amelia, do you have any, any data with this Augusto, most of the babies which we get are, um, you know, the ones that can be managed at Chelsea, and of course there are then the severe ones which we then refer to King's, you know, King's is one of the centers that goes in for feto. So unfortunately I will not be able to give you that data because this is the lost patients. They do not come in our series. But yes, uh, we refer to kings and, uh, of course, you know, now that uh Jan depressed is also now uh in London and of course as part of the sacro coccygeal teratome or the, I'm sorry, meningomyelocele part of the problem, but, um, so I do not know if he's also doing any of this, but King's definitely is taking and plugging these children. OK. Uh, in, uh, Sweden, Carmen, Carmen Mess. Burgo says in Sweden it's around 30%, so very, very high. There's definitely variations, yeah, that happens that in Cincinnati, at least, uh, because it's a reference center and having this low rate of terminations, so we don't have a filter of the bad cases. So we have a lot of deliveries in very, very, very severe category. So, we have to put many patients on ECMO and deal with these babies. Still, we have 50% survival in this more severe category on ECMO, but, uh, but really, they are very challenging babies with a lot of problems. So, but still we have 50% survival and hopefully with the FiO, we can, we can rescue even more. There's one question to Professor Saksina, um, about the dome-shaped graphs that you mentioned. Are they ready to use or do you have to tailor them? Um, Well, uh, you have to dome, uh, the dome shape or the cone shape, uh, um, uh, patches, you have to tailor them yourself. And, uh, there is one of my recent publications which I could then share. I think the cone shape is a shape which is generally practiced with a lot of groups, but it gives you this dead space on the top. When I make the dome shape, it has more of a physiological shape of the diaphragm. So what I try to do is I just Curve up this edge, and put a suture line on this side and the other side, and I put it. Try to be very liberal when you're going to do these patches. You will be totally surprised that you will have a big cup like this which you're trying to place into the chest. Don't be worried about it. Nice sutures, a lot of rib sutures in the front and back, medial side. It's always an issue, and as I said, you're not going to put the stitch through the aorta. You're not going to try to touch, disturb the esophagus. Those are the stitches which you have to be careful. But generally when you use large dome shape, it does not herniate because you've given the gut enough space over there to accommodate. If you make it tight, that's where the gut tries to herniate outside. So experience with dome-shaped patches has been generally better with regards to re-herniation. A question to Jose Luis, uh, do you see any differences between the two groups of graft versus muscle flap in terms of, uh, postoperative gastroesophageal reflux rates? No, it's actually the same. Yeah, I think it's a very, it's more depending on the position of the stomach in the chest during the utero life and then the reposition in the belly. I think it's more, um, the, the stomach lose all the uh mechanisms of anti-reflux, uh, and I think, I think it's the problem, not, not the repair itself. So the same. Uh, can I just make a point on this reflux? It's a very important thing what you mentioned also, uh, Jose Luis. Uh, of course, in these larger ones, you completely lose the angle of his in the stomach, and you have to go in probably at a later date to do these procedures. And if you have a patch, it is so stuck behind that, you know, if you're trying to do one of the Nissans or the Thals and trying to put, there is no diaphragmatic stitch over there because one part of the cruise is missing, in fact. So in these children, if I have to go back in again and do a anti-reflex procedure, my opinion is not to touch the back. I do a thal procedure, you know, a front wrap, so I'm not trying to find a stitch behind over there, and, uh, this is generally how I try to come out of them. Yes, I agree with that. So I am, I am coming from the school of Boocho in Barcelona. It's a very similar dental, and you don't need probably the Uh, 360s of wrap to, to complete that in these babies. But yeah, still we are doing Nissan and Ts, yeah. OK, that's a totally different, uh, even more complex discussion on the reflux. Um, I think as we have, uh, uh, we are over the hour already, we need to have maybe short answers. Lutz Graumann is asking who's performing simultaneous, uh, adhesolysis? Um, are you doing that? And he's also asking, um, any role for poster monitoring, um, routinely of intraabdominal pressure. So I, I, I don't used to do this lysis of advances, uh, but I need to admit that the last 34 years looking at my partner Doctor only him that he, he used to do it. So I am doing that also. I, I don't know if I'm doing something useful or not, but you don't lose too much time to do it. And uh the second question was, um, Intraabdominal pressure monitoring other than urinary output? No, we usually, we usually, uh, ask the anesthesiologist and, uh, we monitor interoperatively. If there's any doubt about, about, uh, the pressure, we usually put a mesh, a temporary mesh to extend the abdominal cavity. If we finally close, yes, so we do for 24, 48 hours, uh, bladder pressures just in case. The recurring question about uh it's opposed to Amelia, but it's actually about uh what if you know whether uh Dario Fauza in Boston or somebody else is doing research with amniotic and chem stem cells to grow a mesh to be used as tissue in CDH patients. So a lot of research went in the last 20 years, different uh type of cells in type of dev in developing tissue engineering for the diaphragm. But I think the clinical reality is quite difficult. Uh, how to source the cells and how to use it exactly in the patients, the cost of it, type of defects, every centimeter is going to add €20,000 more to your cost of developing. So there is an article which I've recently published in Pediatric Surgery International, which shows all the problems of tissue engineering, you know, in the clinical uh context. So, nothing has clinically come in at the present moment. OK, um, there's a lot of people, uh, congratulating, uh, about, uh, this webinars. It's definitely very interesting. I think we can keep going for another two hours. Uh, there's, uh, uh, it's, it's great to see that there's people connecting from all over the world, uh, all 5 continents, and, uh, uh, it's, it's always, uh, for us, uh, um, uh, successful to see that, you know, the Yupsa family is growing beyond Europe. Uh, some of the Europeans also are beyond Europe anyway, but there's a lot of, uh, uh, people that are joining from, uh, different time zones, uh, and, uh, everyone brings together their experiences, so I, I really, uh, thank you a lot for, uh, for these beautiful presentations and especially for the discussion that has followed. Yeah, thank you. Also from my side, um, um, you really summarized it very well. A Augusta really enjoyed it again and I'm also amazed how many questions there are and also the advantage of a, a webinar compared to Congress where all these questions from the, a lot of juniors can be answered, um, uh, with this time we take, um, and really like, um, yeah, congratulate the two speakers for the excellent talks and also their time. You gave, put into, into this and um yeah, looking forward to the next webinar, um giving me also the chance to thank Gaia for setting this up again. And maybe Gaia, can you announce the next webinar and what are we doing?