Practical Approach: Intestinal Failure Innovations

Um, I think one of the things I want to talk about, which we were initially talking at the end was the kid with renal atrisia that isn't able to progress with feeds and, and the role of upper GI and endoscopy. Um, one of the questions that came in is when you can't feed, uh, what are your options? And, and I mentioned, you know, the use of post-gastric feeding with gastric decompression at the time. We certainly have had experience with some kids that have had really poor gastric emptying where surgically we provided access to the jejunum just at the ligamenta trites with, I put in a mickey as a way of directly feeding with the gastric tube decompressing at the same time, and Conrad and Sam and I all have patients we know well that have been able to be managed that way. The other thing that I do as a routine is some of, always with the nutritions, I try to get a primary, um, closure, but you can't always do that. For various reasons, and when you have distal bowel, how to manage that with a mucous fistula or or whatnot is, uh, an ongoing question that many of my colleagues ask me about and I have developed a way of just placing a 3-4 French feeding tube in the distal bowel and not maturing that as a mucous fistula but bringing it up as a stand. And bringing it out the abdomen as a way to provide distal feeds that all the nurses have to do is take a syringe and basically inject distally in and for the atrisia kids and and even like the CF kids where you don't want to instinate the secretions, the ability to routinely refeed, which is what the question was, I think becomes very easy. Easy because it's just a cap too and it's not having to access place catheters and get a seal and worry about the leakages and with that strategy I do think you see significant benefit to the children not just with fluid and electrolyte absorption but also the ability to get that bowel to dilate up and to mature. And I think at the time of takedown you have the ability to maybe decrease some of the technical issues and the problems that can occur with that. So I think Cartland has some, some questions or some points to add to this. I, I think that there are a couple of those are very good points and the question that came from the um from the feed here was was an important one, Mike, you mentioned doing a, uh, doing a feeding geostomy just distal to the ligament trites as an, an operative enterotomy, if you will, with the, with the balloon catheter, you, you mentioned a skin level device that. I have always felt was, uh, I, I was always concerned about that being obstructing so that you do have to drain the, the proximal bowel if you're going to put a balloon catheter into the jejunum. So when I do that, Cartlin, and I, I don't have a figure of this, is I actually divide the bowel about 2 or 3 centimeters distal to the ligament of trites, and I bring out the distal bowel as a chimney, if you will, about 3 or 4 centimeters with a. And the side anastomosis and so this proximal jejunum is brought up over the left over the the the splenic flexure of the colon so there's no window by which um intestine can volvulize, which is a problem when you bring up a loop of jejunum in the middle is that you're creating a potential um site for bowel to twist upon and when I do that I can put directly in it a mickey button and Yes, the balloon is blown up, but it is not in the luminal flow now and so when the tube comes out it's just like placing a gastrostomy tube back in so you're not doing GJ changes and distal changes and the moms can manage these tubes at home. And now that my GI colleagues know I do this, it's become all the nurses and staff are used to, uh, the G and the J but. That's the technique I use that I think helps with the longer term access to post gastric feeding that doesn't require interventional radiology, changing GJ tubes, and not putting anything in the luminal stream that could potentially obstruct. Yeah, I agree that's that's exactly the way that I do that as well, and I think it's important for for people to recognize that just putting a balloon into the lumenum of the small bowel is, is obstructing. And that creating a chimney, if you will, with a small roe limb gives you the opportunity to put a balloon catheter in that's easy to change. Family can change it just like they would change a gastrostomy tube. You don't have to run back and forth to interventional radiology for changing a GJ tube that can obstruct and can erode. I want to offer one other alternative, uh, and, and I used to do the same thing where I did the side, and, but now I do. I read a paper. I'm trying to think who wrote it. I think Dan Osley. But basically, you just take, you make a J pouch. You just take the, the, the bowel, you make a little enterotomy, and you put a staple down. And then sew that up to the, uh, abdominal wall. So then you can put a mickey button in that. Um-hum. And it doesn't obstruct the flow. So that would be easier to do laparoscopic. But the only thing to do, but the thing that does differently, and it's great laparoscopic cause you and Dan like that, is that you've just doubled the amount of intestine you needed to place it, and these are kids that I'm worried about. You make it small. Well, you're still at doubling the length. So all you've done is bought yourself 3 or 4 centimeters of bowel. Uh-huh. Um, when you double that up and you bring, you're really, Requiring enough to get up to the abdominal wall that functionally when I only have 40 centimeters of bowel, I would not feel like I was capable of using that much real estate, uh, for what and laparoscopic surgery is not really the driver in the concepts. I, I have to think about it because I'm not sure. I, I totally, I'm, I'm trying to think we can talk about this later. By definition, you've doubled the amount of intestine you need to do that because you've made a loop, but you have your chimney. So my chimney is, is literally taking the bowel with a single arcade up. You can't make a chimney that you have to have 2 or 3 centimeters by which a balloon can sit in. But if you've doubled the length to do a J, you've doubled the amount of intestine, but remember that's all in continuity. So the entire thing is no chimney is not being, I think that's worth, that's worth discussion because I think that you probably aren't losing any length if you create, if you create. This versus creating this, I think you're probably about the same. I don't know. I haven't ever done that we'll debate and then post it on, and again, this is intestinal failure, so I say we get off the boxing gloves and just see. Most of, um, I would say that most of these kids have such complicated problems that they've had 234 laparotomies and laparoscopy is going to be problematic anyway, so. They're not all, they're not all appropriate candidates for laparoscopy, but it is an easy recovery, and you probably don't, and actually the laparoscopy is not the reason to do it. It's that you don't have yet another possibility of another stricture because you don't have the, uh, uh bowel anastomosis. Uh-huh. That's the only reason I do it. I get that. Uh, another point you brought up, Mike, was the, uh, distal feeding and irrigation if downstream to a stoma. So, so if you have a proximal stoma, I think it's important to have access to the distal stoma. We'll see kids that are brought in that have a distal stoma and no access to that or a distal remnant that does not have access, so there's no distal stoma, and I think it's important to expose the distal bowel to luminal nutrients. And if you can have access to the distal limb of bowel, I think it's important to preserve that access. So for the surgeon that is creating the proximal stoma in the case of necrotizing enterocolitis, for instance. I would prefer that they leave access to the distal bowel as well. Yeah, and, you know, the other thing, Already placed in a way that I don't have to do anything other than just mobilize proximally distally, it is not as stressful on me or the baby as doing a complete laparotomy, finding the proximal distal bowel, and getting it together. So I think all these strategies, I think, uh, play a big part into, um, I think how some of these kids are managed and how they do. Yeah, Mike, Michael has taught us well. I mean, it's, uh, uh, even we as gastroenterologists, when we see a patient from elsewhere where the, the jejunostomy is in the, in the right upper quadrant and the, the mucous fistulas in the, in the left lower quadrant, we know. That's, that's a recipe for trouble. Um, I wanna, um, Zach, if you, I don't know if we can do this or not, but I wanna try to zoom in as we talk about surgical stuff today. I'm gonna ask the faculty to draw on their papers so we can show people. So this is what I think Mike is talking about. Is, and Zach, I don't know if you can see this. This is the way to do a, a, um, a mucus, a, a feeding, a, a general feeding tube by putting in a button. You don't have to do a, a stent and so go ahead and explain the issue. Oh, so what I do, explain how you do it, yeah. This is drawn a little differently in that this is the ligament of trite. So this bowel is tethered, right? So this is the distal duodenum. So it's not going to be able to. Up here because this part is fixed. Good point. And so all I'm doing is taking the first arcade off of the fixed point and bringing that up here as the first chimney and then doing an end to side anastomosis, which I will argue I have it down. It's not the most logical thing to do because this is fixed to the baby's back, but it's a great point that this is the way to put a button in, but this is how to put a button in if you wanted to. More distal and bring up a loop you can do what Todd is saying here and maybe if you have a good blood vessel here it's only maybe utilizing 3 or 4 centimeters but you now have um a space by which something can uh become incarcerated in because this tube doesn't go straight up it goes actually off to the left and what lives over here is the colon and so you. Able to put a stitch here laterally so there is no space. So over this is from the retroperitoneum out to the lateral side of the baby is really not a potential space. So I've never seen an internal hernia this way where I have seen with feeding J tubes that are not done like this, leaving a potential internal hernia site disasters, and these are not patients where I want that risk to occur. I don't, did I win? I didn't. You win, you win. Yeah. If I may ask a question, the timing of the surgery, this is some, you placed this tube at the initial surgery or later on? No, so I, I think the, the point is this is not a common surgery that's done, and we certainly have had children that have had disc motility problems where they've had really bad motility. We've distally been able to feed them with gastric emptying and we, Want to send them home and the kid only weighs 3 kg and if I put a GJ tube in that kid, A, the tubes are very stiff and there's certain risk that goes with it, and B, those tubes are not durable long term and when they're displaced they require families which often for us don't live near our center to come back for a radiographic exchange of a tube. And so in conditions where we project a long term need for distal feeding. We've done these GJ tubes in the NICU and gotten them off of TPN and then they use this at home and Sam, for example, can tell you a few of our patients that this has worked reasonably well and been able to get them off of TPN to go home and then some have over time been able to regain gastric emptying and some have not. Yes, that's absolutely right. I think that it's when you use when you attempt to use a GJ. If you have a dismodal duodenum and a mega duodenum, it, it, it invariably will flip back into the stomach. The tip of the, of the J will flip back into the stomach, so you're, you're really, um, having to replace these almost weekly in some of these patients. Um, so these patients, though, um, we will feed distally and we will oftentimes just by draining the stomach, we'll be able to decompress enough that eventually they regain function. We've gone as long as 1 year to 18 months with some of these devices very successfully, and patients have eventually regained function. Um, it's, um, uh, it's a handful, but yes, we do see improvement in function after a while. I want to extend Valerie's question, a question for the and for the virtual faculty. I have a kid who, let's take an example, Midgud volvulus. I'm in there. I know he's going to have a problem. Should I be putting in a G tube at the initial operation? Uh, are there any virtual surgeons out there? Actually, well, anybody, because when I was in DC it was the gastroenterologist that was asking me to be putting in, uh, G tubes at the initial operation, and I don't know if, uh, if that's, I don't do that routinely. I will tell you, if the kid is a volvulus, it's a kid coming in who's one who's been enterally fed all their life and is going to have excellent PO skills, um, I don't know that. It's the same as an infant that comes in at the first week of life that has never done great, has a volvulus, and so I think in part it depends on the age and where we were with feeding. Sometimes original surgery is one in which A gastrostomy is not placed. I, I do in, in situations where I feel like I can and it's safe and it's long term, we'll place G tubes in in the in the in a very small premies where that's been a challenge, and we had a couple of kids that were 700 grammers total intestinal wall disasters where I knew I needed to. Gastrostomy tube, but certainly that kid is sick. I've actually done the same as my distal feeds where I put a 3 French feeding tube out the stomach and just coiled it and left it there. And interestingly, 3 or 4 or 5 weeks later I can pass a wire in the OR with interventional radiology, dilate it up and put a primary tube through that site because I preserved. it, not exposing the kid to another surgery to place a gastrostomy tube, but I certainly didn't have the opportunity at that point. The abdominal wall opened. I didn't have domain, so access to the stomach has allowed us to go back later creatively and provide gastric access without exposing to a second open surgery. OK. I, but don't you, you mentioned in the beginning about whether or not they can eat. But, but don't almost all of your patients need some sort of initial, like we talked about in the beginning. A gastroscopy? Yeah, they need tube feeds, right? They need, so if they all pretty much need it. Shouldn't, should they all be getting a G tube? I think that if if their oral skills are good and they will eat by mouth, I would prefer them to eat by mouth. I think you find people who have evangelical conviction about about drip feeds versus versus bolus feeds, but you know, I think that the most physiologic, the most normal behavior approach is probably a preferred approach. It looks like going back to the very beginning. Of the audience, almost 60% liked the drip feeds that's versus the bolus or the letting kids eat ad lib. So this is clearly not agreed upon by definitely you find controversy about that, and I think you'll find people who feel very strongly about it. Well, I think, I think both have their advantages and disadvantages. I, there's no question, at least from there's one classic study by Jolie and colleagues. Done in uh in a French cohort of adults where they actually used a polymeric nutritionally defined formula in adults who were normally hyperphagic and the hyperphagic adults who had short bowel syndrome who were left at their own devices, uh, had about a 60% absorption uh coefficient, uh, nutrient absorption coefficient by bomb calorimetry. Then they took these same adults and they took that amount of calories and gave it by drip feeds and it went up to about 85% absorption. So there's no question that that continuous drip feeding improves your absorptive index. But then what they did was they took about half the calories, let the adults eat that, uh, and then fed them overnight. And found that it was about 75% absorption. So, so maybe it makes some sense to feed by drip feedings at night and let the patient eat during the daytime and to combine the two, the best of both approaches. I wonder if our colleagues have similar approaches or what what they do in their institutions. Maybe, Rob, what do you do with your patients? Well, I think it's Like you kind of alluded to, Sam, I mean, it's very individualized based on the foregot motility or dys motility, um, the age of prematurity or the age at which your onset of the volvulus situation in a toddler, obviously much different than the neonate. But, uh, when we can, uh, trying to be as physiologic as possible, um, as Doctor Burns had mentioned, I think is, is certainly the way to go, uh, but, um. At other times when we're really hampered by forego dys motility, feeding post pyloric, and in a child who has otherwise good length of intestine is something that we would entertain. So hard to kind of, um, uh, give a blanket statement for, for this one. OK. I'd be interested to hear what they do in the UK. Yeah, I mean, I would agree with, uh, Rob. It's the heterogeneity of the population is such that, you know, it's difficult to generalize it. It has to be individualized. And, and, and secondly, however you get feeds into this child, it is very important to get some feeds into this child. And, and then the physiological approach can be worked, because, you know, it's quite important. In the initial instance to try and protect the liver as much as you can by enhancing enteral feeding, and, and initially we will continue, we would, we would advocate uh tube feeding, but we will never say no to breastfeeding, uh, like any other center in the world, but we will always. Uh, try with tube feeding, and we've been very successful with giving tube feeds during the night and trying bolus feeds during the day to try and then give them uh uh nights of PM and and enhance their internal adaptation, so feeding is very important, whichever way we can do it. Yeah, and what started this was Todd's question of do we put gastrostomy tubes in kids, and I, and I would say it's hard to give a generalizable answer. It's some of our kids are neck kids that are sick. I, I think a gastrostomy tube is exposing them to increased risk if you're sick at that time. And certainly the kid that's otherwise full term that has an atresia, um. You may think that they're gonna need long term, but you know, certainly there are are ones that do quite well and long term may or may not need it, and so there are certainly ones that I've put them in and ones that I haven't, and, and the gastrostomy tube is a need, but you have access to them in a way that you're not lacking the ability to do things because there's not a gastrostomy tube in there and so the. Timing, I think plays a role, especially in these smaller kids, because if you're gonna need a long term tube and let's say it's placed up against the costal margin, it's not in a good place, there's a lot of leaking issues and stuff, um, uh, you, you, you don't get it free by putting a gastrostomy gastrostomy tubes come at a cost to these kids and so, um, I don't have your answer. I can tell you individually why I didn't, didn't do it in some. Patients and I, I have regretted doing some and I've regretted not doing some so, um, I think some of it is just our inability to see the future and to know, um, the things to do to state the obvious opposite thing is a lot of these kids are not fun to go back in and re-operate on, not at all. And so, so you have to take that into mind and I mentioned a few of those kids to you and the fact that a small kid isn't gonna tolerate some of. These tubes as well and that if you just get access to the stomach um you uh you give yourself an easy way to get a gastrostomy tube later that doesn't require that and that just requires you having thoughtful ideas just like where you put your stomas so that you prepare for the next step uh at that time and reduce some of the problems that we all have had and so the time to have thought about that is in. Operating room and so that's what fellows are good for too because they sometimes remind you of that because you've reminded them on other cases why didn't you do that so um again I think it's good to discuss what you're doing out loud when you're doing this in in the formation of teaching because it reminds you to go through all these different things at the time so that you're you're weighing the risks and benefits of doing each at the time. I can recall several cases where we've actually removed gastrostomies that were not functioning properly and the children have done much better. You know, you have a gastrostomy that's all prolapsed and you, you watch the parents try to feed them through the gastrostomy and 2/3 of the formula is coming right back out. And so when you close that gastrostomy, the child thrives. That's a great point. Awesome. So I, I think this is really an important thing. So when we were finishing the last session, we had talked about the kid that we couldn't advance with the jujunal atresia. And so I'm gonna throw a scenario to Cartlin that says that we were convinced by our colleagues as surgeons that this kid had a mechanical problem. So this kid. Now 2.5 months old, has not advanced more than 20 per kilo on enteral feeds, and our colleagues have convinced us that there must be some mechanical problem in this dilated segment of proximal bowel. So you operate on the child and you see certainly that in fact there is dilated segment. A bowel your anastomosis, you're capable of getting content across and although it is definitely a discrepancy in size, you don't know that there is a mechanical stricture there and you see nothing else. What, what is your option? What is your management options for you to to take care of that problem? If I was convinced to go back to the operating room for what was presumed to be an anastomotic problem, I would never leave that anastomosis alone. If I found it to be patent and And what appeared to be open, I would still revise it. I would do that? I would change that so that I would most times I want it to be a straight end to end if I can, so I wouldn't necessarily do, say, a strictureplasty like you would do for a Crohn's disease. I would do more of a, uh, a focal resection of the, just the anastomosis. But you're still going to now have a size defect, and you have a big piece of bowel going to a small piece of bowel. If you revise it, you still have a big piece of bowel and a small piece of bowel. You can still, you can still taper it so that it's, uh, you spatulate the distal end and it slides on and, and it may not be exactly end to end, but it's. So, you wouldn't consider a Heineke Mickel it's a cost, To just increase the luminal diameter per se, I wouldn't say you know one thing I think that is important in intestinal failure operations is that you never say you'd never do something. You always, I think it's more important to at the end of the operation. It's really more like artwork than it is like science. You want to look at the intestine and know that it's beautifully aligned, that there's no kinking, that there's no restriction, that every anastomosis, every. Manipulation that you've done is functional and that at the end of the operation there's there's nothing left that you feel like this could be a problem, but I think it's all right. You can't tolerate that when you leave the operating room, you have to think everything here. Will work, yeah, and that's the art of surgery and, and for our colleagues that don't do that is they ask you why you decide and it, it really is, um, a personal decision. So you do that and, but now you have, let's say the 1st 25 centimeters of this patient's bowel is just huge. What are you going to do in the distally, let's say the kid has, let's say 50% of their estimated bowel length. So 2/3 of the bowel is distal to anastomosis, 1/3 is possible, and it's 7 to 1 dilated compared to the distal. It's just big dilated segment of the bowel. What are you going to do with that bowel? Well, I know, I know where you're headed with this. I think that the question is, is the dilated bowel something that you would step routinely, or is it something you would do a Bianchi, or would you taper or leave it alone? If it's chronically obstructed because of an anastomotic obstruction, then you might say that this will improve. The dilation will improve over time. But I think that in the past it's always been the default would be to do a step procedure and decrease the diameter, especially if you're having issues with bacterial overgrowth, if you're having problems with recurrently infections. Or d lactic acidosis, then you're more inclined to want to decrease the diameter of the intestine to help this patient. This patient was only unable to advance on feeds. I think it's a, it's a judgment call at the time of the operation and, and to have a consistent diameter, I think is something that deserves, you know, has some merit, whether or not that patient should have a step or a Bianchi or. Tapering, for instance, I've, I've, I've always tried not to do tapering because I don't want to discard surface area. So I, I mean, I, I, I had a couple of, of bombs in that question, and one is that this kid has 50% of their estimated bowel length and if you looked at our slide before, we recognize that our expectation of a child with 50% of their bowel length is that they're going to come off a. Parental nutrition and that I have seen people trying to salvage bad bowel in the face of what otherwise is good bowel that's being brought down because of the concept that every centimeter matters and so I think the key point in this patient in my mind is too is that um you need if you have a mechanical problem that you can directly associate with that dilated bowel um I think. It is a logical thing to do, and I'm not compelled to address that because I feel like the obstruction may have been in part causing that, and I relieve that and that's the temporal order of things and that I don't have to do two at once if I'm not convinced that, and I revised it because, but I'm not convinced that that was the problem. I think the mindset of tapering versus lengthening. Uh, of that bowel has to come into depart with this graph is telling you this graph is telling you with that distal bowel your expectation is that this child's gonna be OK and what you wanna do is make sure that you're not overtreating but you're not also missing stuff. So in my opinion, like you at a 2 month old, my, my opinion is that the step procedure done. In the first year of life, first, certainly the kid that has not progressed with enteral feeds is not beneficial unless you are specifically avoiding line infections and bacterial overgrowth. Um, this modal bowel does not become modal because you did a step procedure on it. If you haven't been able to advance feeds, the step procedure is not going to make bowel that didn't. Work, work if it was working once dilated and it's not functioning well now over a time period is a different scenario than the kid that's never fed and the point I started this whole conversation on, which is so logical but needs to be restated, is that the one thing that makes the bowel adapt is feeding the bowel and procedures in which you have. Problems in reinitiating feeds have really caused damage to that patient. So if I were to have to do something to that dilated segment knowing the bowel, I, I would taper that that bowel and in this scenario, I don't think there's a role for a step, and I'm, I would say a step is a mistake in this patient. I would love someone to argue with me on that. Hm Anyone, I think I think it's tempting to want to step every dilated piece of bowel, but it's not necessarily the right thing to do. And certainly in the younger patient, I don't know if you'd choose a year, you'd choose 6 months, but certainly a 2 month old child hasn't really had a chance, especially if you have an anastomotic problem that's causing even a partial obstruction. I, I would agree that it's. Probably not the best idea to step just because you can. Lengthening isn't necessarily additive. So there's a paper that came out that was from the step registry, and they used it as a proof of of safety that step procedures can be done in the in the early neonatal period. And if you look at that paper pretty closely, what you'll find is that um the kids that had step procedures, I think. Only 3 of them ever ended up coming off of parental nutrition in that study, and if you look at our natural data, we expect that well over 80 to 90% of these kids as described will be off of parental nutrition at 12 months. And so that's just because they're able to be fed. And, and the kids that have had steps in our experience early in life have often then redilated and undergone second steps and have had mechanical problems that Sam can talk to that have led to mechanical obstructions of the bowel that have been very detrimental in the ability to feed, which I think is is one of the biggest mistakes that can be made. In this population of patients, so I think the idea that steps can be done safely is not the question. I think the question is that is a step procedure giving you a benefit over the adaptive response that occurs typically in a patient based on data compared to other patients not managed with the step. And those data don't necessarily exist, but that that's in part what I have this slide here for you to understand that um you should expect that patient to do well, and I think they should have an opportunity to do well before you expose them to a surgical procedure which and and even though the step registry would say um. Doesn't have the greatest of long term outcome in that early patient population. I think it's important to recognize that what you look at is can an operation be done safely or without complication doesn't necessarily make it the right operation for that patient. So The notion that you can do something doesn't necessarily mean that you should. Yeah, and so, and, and our, so people ask us what's the indication for a lengthening procedure. And in part, the indication for a lengthening procedure for us is, uh, complications known from bacterial dilation that relate to bacterial overgrowth, uh, dillactic acidosis, um, or perhaps the child that is ultra, Short and has a segment as you suggest that that is very dilated and it just doesn't make sense to taper and so it does make a rational thought that you would not taper a kid that only has 40 centimeters of bowel and that uh Bianchi's and steps are are logical approaches but those are generally not decisions being made at a 2 month old or a 3 month old but really. A kid that is really after his first birthday because there's other management strategies you should have. I think the expectation of going from 10 per kilo of enteral feeds, you're doing a step and that kid's gonna be off a TPN in 3 months is a fairy tale that belongs. You're in Orlando, right? So that belongs in Disney World because that doesn't exist. That doesn't even work in Disney World and so, um. Even the Magic Kingdom that doesn't work. So, um, I, I think people need to recognize, um, when and how to use a step procedure and I do think the the biggest setback to our field of of intestinal surgery for this problem is that the surgical, the, the surgeons themselves are not doing techniques that are out of the realm of any pediatric surgeon. But when done in in isolation without a team and a consideration of the fact we've been talking about today, even when done perfectly well, uh, and absolutely no different than how we do it here, the outcome is gonna be different, um, and so I really think when you do your surgical decision tree, it's done in a multidisciplinary way. I think you're gonna get, uh, better comments. I'm interested to hear Simon because I know they have a lot of experience about this in Seattle. Yeah, I know, I agree with everything you say. There's, there's, we, we see a step from the non-combatant's point of view, which is mine, um, is a pretty straightforward operation, and every pediatric surgeon sees a bit of dilated bowel and puts some staple lines on it. It doesn't, it doesn't help. I think you have to have very clear indications recurrent. Bacterial overgrowth, as you say, or maybe those patients that have just got another 10% to go and you can't quite get them there. But um, but overall I would say just because it can be done, it shouldn't be done and we, we see all sorts of complications including ulceration on staple lines and uh obstructions, increased disc motility. I don't think that it's an operation that we just throw around willy-nilly, and if a if a piece of bowel is nonfunctional, it's going to be just as non-functional if it's longer. So if you, if you can afford to lose a bit of bowel, then, you know, get rid of that bad bit. But often I find, you know, the anastomosis, even if it's not physically narrow, um, does, as Doctor Burns said, does need, need revising and And it is a case of individualizing the operation for what you find in that patient. But I've got to say our relationship with our surgeons is such that we will, um, you know, we'll do operative, uh, endoscopy. We will get called in and say, look, this is what we found. Let's make a decision together. Um, and I think that that works. It works well for team dynamics, but I also think it serves the patients, uh, best as well. So over at UK, Ghoresh, is there, is there enthusiasm to lengthen bowel in neonates? Um, no, I think there is only one center in the UK which has all the enthusiasm to do non-transplant surgery. Uh, rest of the centers in the UK are a bit conservative about non-transplant surgery, and as all of you have said, it is important for us to define when it is going to be beneficial. It is important for us to sort of. Know some of the patients well and, and be reassured that all the feeding management strategies that could be tried to promote internal adaptation have been tried. Because, you know, all of us are in a situation where sometimes we get patients referred from other centers saying, would you consider a non-transplant surgery? And, and it's really difficult for us sometimes to make that decision, because we don't know the patients so well. As, as those patients that are following up in our center. So it's very important to get to know these patients well before you make any definitive decisions about non-transplant surgery, as well as define what your, uh, benefits from the non-transplant surgery are, whether it is lengthening, whether it is step, uh, or whether it is tapering, that's, I leave the decisions to the surgeons, and that's where the multidisciplinary, Uh, team effort comes into the play, but clearly, ma'am, uh, you, you know, pushing for a step procedure is not the way forward in the present, uh, we would rather continue with feeding management strategies and then when we are absolutely stuck, cannot advance feeds, feel that there could be an obstruction, and then if the surgeon goes in and, and has to do some procedure, uh, uh, then that's acceptable. Or, you know, like Simon said, you know, you want to just finish the last leg of the, uh, race to get him off the PN, then that's when you will consider non-transplant surgery very carefully, defining the actual benefit that you will get from it. Yeah, so, um, I think our center here is fortunate because Sam does both intestinal rehab and transplant, and I think historically a lot of the intestinal rehab programs like the Pittsburgh one were based on strong transplant programs, um, and since the last 4 years we've been doing this, um, we've not had a kid transferred here with, uh, non-congenital neuropathy like tufting or whatnot. Um, or Hirschrungs that have gone to transplant and have been managed very successfully, and I think Sam can speak to before and after and the effects of, of an intestinal program on a transplant program. Oh, I, I, I think it's it's extraordinarily important and that's, I think, a model that should be emulated where people have a foot in each camp. Um, uh, Monique, for example, has, uh, is a board. Uh, eligible transplant hepatologist and, uh, and, but she's also done a lot of work with intestinal rehabilitation. So, so that, that they're really truly integrated programs and, um, and I think it's extraordinarily important that, that they're within the umbrella of intestinal rehabilitation transplantation should be an option, but just one option, um, one should be able to. Viewed intestinal rehabilitation as an effort to to emancipate the patient from from parenteral nutrition by any means possible. And if it if it does require transplantation and if all other means have been exhausted, then transplantation should be done. I think it's um it's um we've Since we've matured our, our multidisciplinary program, our, our number of transplant candidates has, has declined by 75%. Um, our internal transplants are almost non-existent now, um, and, um, and external referrals have, um, have, uh, have continued, but we've been able to. Um, to manage a number of these patients, uh, without transplantation, um, and I think Jeff can probably speak to the same point, and, uh, uh, and in Pittsburgh, I think, uh, your number of transplants has declined as well. Is that, am I correct? Yes, you are correct. The, the number of actual transplants, and, and actually the, the, especially the number of um combined liver intestine transplants, um, uh, speaking to the preservation of liver function has gone down, but also the, the, the number of kids that um. That we have a transplant. And of course, some of that initially trying to say. So I think that we work um well with the, the, the intestinal uh transplant uh surgeons. And, and I agree with Sam, so a coordinated approach is important. I sort of see our roles as um independent but parallel, uh, with, with parallel goals. Um, and, and our role pre-transplant for kids who come in for evaluation is actually to determine whether or not their medical therapies. Uh, uh, non-transplant surgical therapy, is there anything else that we can do to help avoid transplantation, uh, to begin with? But I, I think the, the, the, um, um, as, as, uh, Sam has mentioned, that the, the internal candidates for transplantation have seemed to have, have gone down over the years. And, um, and I think that overall, the, um, the number of kids that we're actually listing as opposed to following and trying something else first, uh, is, uh, has gone down as well, so. I, I, I agree with you completely, Sam. So I, I guess, uh, I guess the next question is when should we be getting referred patients? What's, what's the ideal soc can speak to this because he's been on. Uh, in Pittsburgh and he's now in a, in a center that has his expertise and others around it, so certainly the surgical expertise exists there. But, but when is it appropriate to involve, um, programs and then I'll have Sam or Mo talk about how a referral program or anyone else out there, how we get back to the local area to allow their care to be done locally, which is ideal for, I think most families. Well, I think in a in a center that has transplant availability like Cincinnati and Pittsburgh, those children are frequently referred when their when their local people think that they're appropriate for transplant consideration. Where I am now, we don't have transplants, so those kids, for whatever reason, those kids will come earlier. They'll come to us for advice about nutrition management. They'll come to us for this conversation about whether or not. Surgical approaches are appropriate, and I think that from the standpoint of what we would prefer is as soon as a patient is identified as needing a comprehensive approach to their intestinal rehabilitation, that's the appropriate time to send them. I think it's not when you have complications and you've exhausted all of your all of your local knowledge. The time is when you when you recognize that this child needs ongoing care. And we do far better with a child who does not already have complications of their disease than we do with patients who come already suffering from their. Current management schemes, I think the second part of your question about how you coordinate care with the local. People who who originally sent them to you is a is a. Problem that's managed on a local level and we have tended to have the patients go back and serve as back to their local local healthcare environment and serve as a resource for following labs, following TPN, following advancement strategies, and when issues would arise, we would get the X-rays, for instance, to review. We'd get the labs to review. On an ongoing basis, and I think maintaining that open communication with the local referring physicians. It is important not only for maintaining the lines of referral, but also for maintaining continuity of care because many of these children will travel from all around the world and the ability for us to do this remotely is not as good as it is for them to see their local person and look at the catheter site or look at the stoma site or whatever. And examine the abdomen and make an assessment, make necessary changes. So I think it's absolutely vital that you maintain communication with the local referring people. So, so Bob, in, in, in, in California, are you getting kids at the transplant stage? Are you starting to see some early that you can help with rehabilitation and get them back on a management plan that you think is gonna avoid that? I think just as was echoed by other groups, we are seeing patients earlier, uh, transplant numbers, I think in a really good way are certainly down out here in Southern California too. Intestinal rehabilitation is really our, our focus, our efforts, and it's, it's really the, the. Late referral or the child with the life threatening potential complications who is moving forward with transplantation, I think with regards to early referrals, that's something I think we all preach and think benefits our patients, but many times that can be an early referral to an intestinal rehabilitation program which has expertise, but May not necessarily offer transplantation and we work also regionally with a lot of those tertiary centers and so good communication absolutely paramount for ongoing advancement of feeds and advancing the care for these kids. So, so one of the things that Sam and Conrad impressed me on that I don't have the skill set that they do is how well they communicate on a monthly basis with our kids that we actually only see now, uh, very rarely. Sammy you can talk about how managing TPN remotely and nutrition can be done with a local, um, team, including a gastroenterologist. Oh yes, I think it, um, uh, the uh instrumental people, uh, in that process are, are, uh, coordinators, our nurse coordinators. It's extraordinarily important to have competent people who know TPN and who can manage TPN. Um, doing the communication, um, certainly I will frequently call the referring physicians to ask how children are doing or ask them specifically for, for, um, uh, periodic updates, um, but our nurses and dietitians, uh, communicate with the patients, uh, specifically. And if they and we have a protocol of laboratories, tests that need to be done, and the timing of the tests, and we give that to the physician and to the parents, and we then in turn get the feedback from them as to how they're doing. If we notice something's going wrong, we'll contact the referring physician immediately and work out a solution to the problem jointly. Um, the, um, I also think that our, our intake process for transplant referrals is, is important, and I think the, the fact that we incorporate both the lumen team and the, the liver team, um, in the care of these patients preoperatively, I think is important. Maybe, maybe Monique can, can outline our, our intake process. In terms of, uh, you know, specifically how we, uh, we get our referrals, uh, you know, obviously we go through a very complex and, and outlined procedure and and set of tests, as Sam had mentioned. Um, as well as studies, uh, but again, often there's a, uh, there's communication we have a split dynamic here amongst the gastroenterology division. There's a side that kind of deals with, as Sam alluded to, the lumen side, so anything that's really not liver or transplant related, and then we, we have a liver side that is obvious, liver diseases or any of those other. Diseases that are transplant related, um, there's often very distinct communication between the two teams, which is quite helpful. Um, if there's a child who is particularly complex, um, and requires a little bit more, uh, um, involvement of our transplant surgeons, they'll of course be more on our service, particularly the liver service, um, if there's kids that are working. We're working on a maybe a pre-op, um, or uh, uh, um, an evaluation for a transplant. There'll be more, uh, on the other side of the fence, which again is the Lumen team, but there's always communication beside between both services. And again, as Sam had mentioned, the, the critical nature of the coordinators, which are, are work on kind of both ends of the fence as well is, is very important. So, so Sam, one thing I wanna talk about is how we manage international patients because we certainly have them. And I'm amazed at how we've been able to do that, um, so remotely well. Well, we have a very well developed global health team, and generally they are the contact people. They're the gatekeepers, and they get contacted by either a referring physician or by an embassy of a foreign nation, and they will oftentimes be given a relatively scanty case history. Uh, and, um, we generally then will say to Global Health, please contact the referring physician and get a more detailed history along with, with films and, and, uh, any endoscopic studies or histology that may be present. Um, they will do so and then after we have analyzed the data and, and reviewed it, we then will, um, meet generally as a group among ourselves and have a representative from intestinal rehab and transplant surgery and decide now is this a patient who we should accept as a transplant. Transplant referral or as an intestinal rehab referral and um once we've decided that, then we will almost invariably, not always but almost invariably then have a conference call with the referring physician to discuss some of the details and if possible we'll have the patient there so that we can Skype the patient and actually. Uh, vis visualize the patient, um, and make some suggestions, uh, on therapies that could be tried at home and then whether the child and then make a decision as to whether the child should be referred to our center. No, but let's say some of our colleagues in the Middle East and stuff, we've tailed for the patients and we've sent them back. Can you talk about, uh, challenges of, of managing TPN here locally and, and what we need to do to be able to get kids back to some of these remote places that send those patients? Yeah, uh, it's an extraordinarily difficult problem because in many countries, uh, home TPN is not well developed and, um. We have been able with the right set of parents. Been able to send them back and have the parents educated well enough that they can supervise the administration of TPN at home. Um, if, uh, if the parents cannot be trained properly, then I think it, it is foolhardy to send the patient back to an environment where they're likely to have an unsafe home environment. Um, but we generally Spend a lot of effort, time, and energy in educating the parents. Um, there are clearly some cultural issues. Um, it, um, there are some gender specific issues. Uh, uh, they're, uh, frequently in some cultures the mother or the nanny is the primary caregiver with the father taking a secondary role. Um, we've, uh, oftentimes been able to inculcate. Uh, are, uh, a, a desire to care for patients, for, for children, uh, within the, uh, the, um, uh, male half of, uh, of the union and gotten some fathers to actually do some very, very competent TPN care. So, so it's, it's difficult, but, and you have to be culturally sensitive, but it can be done. Ghoresh, do you have anything to add from the UK because you certainly have a wide brace of referrals there. Yeah, I mean, uh, from the UK, uh, what we do have is, uh, in our center, excuse me, uh, we have, uh, monthly intestinal failure planning meeting. So just like all of you, we get together in a room, the whole nutritional care team, including hepatologists, surgeons, uh, uh, you know, dieticians, pharmacists. And evaluate those children who are referred for intestinal rehabilitation or intestinal transplantation. We hold monthly conference meetings. So we have a teleconference with the, uh, uh, referring hospital. So we have a standard template which we send out to the referring hospital when we first get the referral. The template is then completed by the referring hospital and sent to us with the images. Unless and until they send those images and all the information, we are slightly reluctant to discuss these cases because as you all know, once the cases are discussed, then no information comes through. Or if you don't have all the information, you can't make the right decision. So that's what, uh, we do. In addition, uh, because the UK is a small country. Uh, you have the luxury of following up these patients on a regular basis. And because NHS is centrally funded, there are no issues with insurance companies as such. So you can ask the patient to be followed up in the clinic to see what progress the child is making and whether whatever recommendations you have made to the local team, whether they have been implemented or not. We don't have that many overseas referrals, but whatever overseas referral we have had, we have found it incredibly difficult to convince the families to take up home parental nutrition. Somehow come with the concept that intestinal transplantation is a magical cure, and that, that child will begin to eat after intestinal transplantation, and everything will be fine after intestinal transplantation. And that cultural, uh, sort of, uh, like Sam said, you have to handle it very sensitively, but we have, I think we have failed to convince a couple of families. To take a home as opposed to intestinal transplantation. Doctor Gupta, um, for the, is it, would it be possible for you to pick up your phone instead of the speaker because we're having a hard time hearing you. Is there a way to take it off speaker? Try now. Yeah, I'm sorry, it's just that my voice is also gone because of the sore throat. No, but that's much better now. I said? Yeah, much better. Thank you. Yeah, so I think what we do in the UK is, in brief, we have a monthly teleconference meeting. So we have an intestinal failure planning meeting where the whole nutritional care team gets together and they, you know, sit and discuss the referrals. The template is sent out to the referring hospital and we get the template filled with all the information surgery, dietetic information, growth chart, PN prescription. And the images as well are sent over by link. We review the images and then we ourselves make an initial plan, but then get the referring hospital on the telephone and whatever questions we have, we discuss and then make a modified plan depending on the information that is collected. And since the UK is a small country, we can follow them up on a regular basis, and usually 3 monthly or 6 monthly follow-ups can be arranged. The last thing I wanted to say was that we don't get that many overseas referrals. They always seem to prefer the US, which is fine with us, but at the same time, whenever we get the referrals, we have failed to convince the families to take up home parental nutrition. They usually come for intestinal transplantation. Thinking that intestinal transplantation is a magical cure and that their child will begin to eat as soon as they've had the transplant and everything will be back to normal, and it's been incredibly difficult to convince them to take up home PM and I respect Sam for, you know, whatever efforts he and his team puts in to to send them back on home PM because I can. I can understand how difficult that must be and what the challenges he may have encountered, especially storage of safety and in a very hot country can be very difficult. Those are good points. I put a slide up here, um, the transition to a topic we alluded to, and I think it, it really is going to hit on a lot of things that we can talk about over the next hour, which is the type of feeds that we provide our kids. Um, I'm showing you data on our kids that had either surgical neck or gastroschisis, but it also holds for the medical neck as well that that are fed either by breast milk. Either whether it's fortified or not versus formula only, and the point here is in gastroschisis and the neck there certainly is a significant benefit to the time to wean off parental nutrition based solely on the differences of the nutrition provided, the support that I think breast milk is not just a formula, it is really a therapy, and there's a lot of components in breast milk that. are important. I don't show you data that actually shows that the benefit to kids with spontaneous intestinal perforation per se is not benefited by breast milk, not to say you shouldn't feed those children breast milk, but to say that I think there's components in breast milk that are anti-inflammatory, promodal, that are very important. So I think most people, we can discuss it quickly about the formulas that. We choose. I think the discussion is as much though, and I'd like, maybe I'll go to Valerie with this, is that what happens when you use donor breast milk and you can't get the kids to grow? What are your strategies and when you start to not have access to either mom's breast milk or donor breast milk, what are the best strategies to try to transition these kids as they are getting ready to go home? So I am probably the least person um qualified to answer that question and the reason I say that is because in the state of Illinois um there's been a lot of financial issues and really we don't have access to donor breast milk um for a significant amount of our patients um I may actually like it seems like here in Cincinnati where you have early um interaction with these families that are gonna eventually come to you. I don't necessarily see them early on. And so I think the importance of breast milk uh may not be um important to these families on the onset and so maybe by the time I get um a patient transferred in from me to me, the patient may be 6 weeks, 8 weeks old, or even older, and I've lost the opportunity to provide them for breast milk, so. So, I think this is a, I asked Todd to put a poll out. I'd like to see our, our, uh, people interacting with us. How many, how many, what percentage of patients or what is the predominant feeding mechanism in your institution? Is it breast milk, donor breast milk, or is it formula? Is formula still considered OK? What about here? What, uh, let's start. I mean, what are your thoughts on, on this? If we, uh, we favor breast milk, uh, express breast milk from the mom. Um, we, uh, donor breast milk, we believe is, is less advantageous though it, it can have some advantages. Um, uh, the, um, one of the disadvantages of donor breast milk is that usually, uh, taken from moms who are out. Uh, quite a bit, uh, they, they, their infants may have been, uh, 1012, 14 months of age when they're just before they're about to, to wean the baby, they, they'll, they'll offer breast milk to the bank, um, so that, that donor breast milk is less, less valuable. It has lower caloric density. It has, uh, lower protein levels, and it, um, and, uh, sometimes it's thought that sometimes freezing. May inactivate some of the important trophic factors seen in breast milk, but, uh, certainly express maternal breast milk is, is our favorite approach. And then when we have a patient who is, um, who is, uh, is predicted to do badly, um, we generally go to, um, to elemental formulas, uh, as our, uh, second line. Um, uh, we, uh, occasionally will use hydrolysates, but, uh, but we tend to prefer free amino acid formulas. So, what do we do when you have an 800 gramer, 900 grammer who's already 6 weeks old, breast milk, donor breast milk is running out, breast milk is not available. They're not growing well. Um, they're getting the, uh, We continue that. What, what are your recommendations when we talk about this on Mondays? We, we generally then go to a hydro to a, a free amino acid formula. What concentration, uh, at what age did you say? 6? This is a former 28 weeker who's now 6 weeks old. So now corrected 36. No, we, we almost always go directly to 20 calorie formula because we, we really think that highly diluted formula, uh, loses a lot of its value. So how about 22, 24, 20 we usually start with 20, and I, I think we have to watch out because these, uh, these free amino acid formulas are relatively hyper osmolar at 20 kilocalories, uh, the osmolarity is around 360, 350, um, and if you go much higher than that, you, you, you're increasing the osmolarity. So we tend to. Um, to eschew, um, high caloric density formulas in the very young infant, but then when we do see poor growth, we may gradually move things up, uh, maybe to 22, 24 calories. I don't know about the other places. Uh, Simon, how, how are things done in Seattle? Well, no, I, um, I've done the same sort of thing for a long time. One, if we don't have breast milk available, I prefer to go to a, um, an elemental formula because you know what the osmolarity is. I always worry in these kids with, um, that digestion leads to a change in the osmolarity in the jejunum, and most of our bad kids don't have ileum. So the jejunum has really no ability to absorb against the concentration gradient. Um, and so I like to give isotonic formulas. So that's usually 1517 calories per ounce. Um, and they, uh, providing they don't have a lot of upper GI dysmotility, I find they handle volume much better than they handle concentration. So you keep the concentration low. Um, if they show excellent tolerance, you can always advance the concentration. But that's, that's my general thinking. But, um, once they get a bit older, I find the introduction of, um, you know, baby foods, meats, and, uh, vegetables remarkably helpful in their adaptation process. So, um, you know, although I advocate elemental formulas early on, I think once you can get to complex protein and it's not causing you problems, it's, it's worth doing. Again, we have real problems with donated breast milk. So, you know, if mom's not producing, then we tend to go to a formula. So Simon, your patient is 7 months old, doing fine on an elemental diet, and mom's now giving some table foods and And those are going well. Do you maintain the child still on the elemental diet and provide them ad lib complex foods, or do you move to a more complex? I would usually move to if they're demonstrating tolerance of whole protein, I'll move to a more. A more standard formula. It's easier for the family. It's cheaper. And how do you do that? Do you do it? Do you mix it or do you just go straight cold turkey? It depends on the child, you know. Some of them will swap over quite happily. Some of them have developed a taste for it. And you just have to work your way through it, and it can take a few weeks sometimes with the most opinionated of children. Well, I find it's the opinionated mom that when you switch over the spit ups and that the Elecare is just seemed or whatever is a is a better tolerated formula. And so I see now some kids who are older than a year tolerating table foods, but they're To feeds that we supplement them at night remains elemental, and I wonder if we're not giving them enough stress to adapt by doing that, but the transition phase, I don't think is a simple one, and I think it requires a lot of communication with moms. Certainly they do believe that an elemental formula is medicine in some way, and I think it's about maintaining good communication, good relationships, and. And working through it. And our nutritionists are fantastic. Our dietitians are fantastic at working with the families in these regards. Um, they know the families extremely well. They, um, I think the mothers feel much more comfortable on a 1 to 1 talking things through in great detail with them and, and, you know, that's the real advantage of having many members of the team. Everybody has different strengths and you, you know, it really helps. So, um, I, I want to get to this great question from the audience, but before I do. Uh, because it's a question I've always had, but how and how often are we assessing nutrition? Um. I, I'm not understanding that. Is it, let's, I guess maybe it's different when it's a, a baby who's you're just starting to ramp up versus a baby that you're maintaining and you want to assess how let's start here in the studio and then we'll go out to the virtual audience. So, uh, Monique, how do you? How and how often? Sure, I think it's certainly dependent on the baby, of course, to some degree, but we do have generally have again a standardized approach to how we monitor these kids' nutrition, so the kid's otherwise doing well, growing, again, somewhat depending on the child, but we generally have a series of what we call nutrition labs that we'll follow every 3 to 6 months depending on the baby. And this is someone who's already been. you're not ramping up anymore. Now they're at a constant either I think either way to some degree. I mean, I think it depends again if you're if you're ramping up and you need to follow electrolytes a little bit more closely, say the ostomy output's changing, things like that, that'll be a little bit, might be a little bit more frequent. Let's say you're kind of more at a standard regimen, whether it's TPN, Prero, and El combined. You may, you may be monitoring labs monthly versus, you know, every 3 months. In in some form or another, but we typically have a standard set of labs that we do. So again, baby dependent, whether it's it's a weekly, monthly, every 3 months, every 6 months, depending on where the baby is in his or her course. And Sam, what are the labs? Well, we, we generally do a TPN panel which includes renal, a renal panel, a liver panel. Calci phos mag, uh, calcium phosphorus magnesium, um, we, um, will, um, we, uh, do not, we no longer follow a pre-albumin or RBP, uh, recognizing that sometimes chronic changes are, are much more appropriate to follow. So we, we follow albumin, and it's been part of money, money saving, um, uh, strategy, no longer following some of these more acute, um. Uh, changing proteins, um, we follow a CBC. We follow, um, customarily, we'll, um, if someone's on a low lipid TPN, we'll, we'll follow essential fatty acids, uh, monthly or every other month. We, um, uh, follow, um, iron, uh, ferritin, and TIBC, uh, about every 2 to 3 months. Um, we follow, uh, uh, other trace elements. We follow zinc, copper, ceruloplasmin. Uh, about every 3 months or so, 3 to 6 months, um, and, um, what am I forgetting? I think we've, um, selenium about every 6 months, so the kid is being weaned from parental nutrition in the face of this. So you're at home, talked about turning down the TPN, turning up the volume in the, well, you know, Mike, well. Micronutrient deficiency is extremely common in this group of patients. We found that about 60% of our patients who have been weaned off TPN have deficiencies in one micronutrient or another, and I think Rob showed very similar data in his population. Uh, both, uh, patients who were weaned and patients who are, uh, weaned off, off parenteral support after transplant. So, so micronutrient deficiency is, is very common. We follow B12, uh, annually, um, and, um, we also are a bit more compulsive. We follow, um, we follow, um, uh, uh, methylmalonic acid as a surrogate marker. B12 deficiency as well as uh as uh homocysteine levels, um, uh, knowing that they can be more sensitive than an absolute B12 level, uh, recognizing that uh that B12, um, is, uh, can be synthesized by bacteria, or if you have liver disease, you may have a falsely elevated B12 level. So, so there are a number of factors that we follow. It's like. No, no, no, we're using micro techniques we can do it on 2 mLs. The one other point I want to make about formulas is, and we've not, we've not touched upon this, but there is a therapeutic underground out there of mothers who who communicate electronically who have decided that that blend. Tenderized diets are the best thing since sliced bread for their children with short bowel syndrome bread bread, yeah, right, yeah, juicing, uh, well, it's whatever you want to call it. They, they put everything but the kitchen sink in their blenderized, uh, pureed diet. Uh, have, have the other centers found a similar problem or maybe, maybe solution, not problem. Well, well, so Valerie, I mean, what about you? What you've heard, is there any glaring differences? What about weights? And I want to ask you anything you do different in Chicago? I'm probably very similar to them, um, very close interaction with the nurse practitioners in the family. Um, home care nurses go and actually draw the blood, so I probably get weekly weights or every other week weights on these patients so we can manage this, some of this at home, um, some of the. Families may have a home care nurse that is in the home 8 to 12 hours a day that's also maybe giving us a report and letting us know what's going on in the home. We may see the patient as frequently as every 4 to 6 weeks early on and then space them out over time, but I think a lot with the family, the home care nurses, and our coordinators working with the family, we're able to keep some of these kids at home and manage their TPN, OK. Do you ever, I mean, when you find that they're trailing down, their weights are going down, do you make home adjustments? Do you admit them to the hospital for a week evaluation? No, I think it just depends, and that's why the trends are also very good. You're getting the history from the nurse who's telling you what's going on in the home. I think that. We, I will adjust the TPN at home, but it really kind of depends if there's significant electrolyte abnormalities and I'm concerned that I'm not getting, uh, the full story or there's some concerns about what's going on at home, I definitely will admit them. But depending on the issue, I will definitely, um, um, taper or, um, increase our TPN needs at home. So I, I wanna, there's a, actually, let me ask this since it's right here, do you follow, uh, citruline? So, citruline, um, I guess there's some evidence, um, that you can use it to. Everyone at this, so just everyone at this table just smirks. Maybe there's some evidence you can use it, but I think the issue is there's such large varying levels for citruline, um, so you really have to follow it serially, and I don't think it actually, um, is, um, at least I don't follow it on a regular basis as far as being able to tell if a patient's going to adapt or not, so I don't think it's very, I don't think overall it's beneficial. There's a big need in our field for biomarkers to understand the adaptive process that predicts. The next step, and citrulline is produced by the gut and certainly if you look at the production of it as a total number, you might say the ability to wean off and not off TPN may be predicted has been published before, but as a weekly or monthly lab, it's not informing us anything that leads to a change in clinical care and so it's lacking. What we really need is a blood study. Or whatever you alluded to pre-albumin because the surgeons we used to use that and and whatnot we certainly need to be thinking about it and I think our colleagues doing basic science research need to provide us better biomarkers to understand the natural history by which we see normal patients progressing in a way off of parental nutrition if we had earlier indications that our. Patients weren't progressing as we wanted them to. It goes back to what we have on this slide. Breast milk contains things more than nutrients that are providing a benefit to the patient, and some of the questions out there are, as Sam says, blenderized diet, that's changes in nutrition. So are there others that are supplementing fiber or other things. that they think are beneficial to the adaptive process and then we can talk about that and then lead into therapeutics because certainly there's enthusiasm about mimicking breast milk and uh finding best formulas and considering therapies for enhancing the adaptive response. So let's let's ask who have we not talked to in a while. Let's let's talk to Jeff. With regard to supplements to the, to the seeds, um. Uh, so, We do use uh uh some, some supplements to um uh to, to feed. I, I, I echo again sort of your, your thoughts about human breast milk, and, and again, sort of the hot topic is hemoligosaccharides and, and the fact that we may begin to start seeing more products with polyolligosaccharides or things that might be able to help um mimic uh what the, the milk oligosaccharides are doing, uh, which, which is generally conversion. Uh, into short chain fatty acids, which may add nutritionally, but also add water reabsorption. And that's where uh supplements like uh soluble fiber or pectin, uh, come in. We don't use a lot of pectin, I think, especially if you're using in continuous feeds, it's just a lot of problem to try to, to administer it. We do try to use uh uh soluble fiber. A lot of times it's it's uh it's in mixed fiber components, um. Uh, something as simple as adding rice cereal to the, the, the feed with soluble fiber components to it may help. We're a little bit more aggressive, I think, with some of these, um. Uh, supplements if they have colon. Um, one of the things that was touched upon earlier that we haven't mentioned in a while is the importance of the colon, not only from the standpoint of the reabsorption of water, but you know, I'm beginning to really buy into the fact that you can have actually quite significant absorption of nutrients through the colon, and trying to take advantage of that with some of these supplement products is um is important. I think that there are new um natural lipid products that are out there that we really haven't quite explored as much as we probably should have, should have by now, that can potentially help with regard to uh absorption of fats. We have used things like MCTO in the in the past, um, uh, to help with uh with regard to fat absorption. But, but again, it's not usually something we um uh Do a lot of, I think a lot of the, the supplemental, uh, uh, feed that we do are, um, are basically the, the sort of soluble fiber type products. I'd be interested to hear what other people do as well. What are you doing, Bob? What are you doing out there in LA? Well, very similar to, ah, ah, what Sam and, ah, Jeff have alluded to, I think, um, in terms of other therapeutics, um, ah, the use of probiotics, um, maybe not necessarily in, in, in the, ah, preemies, ah, still, ah, in the NICU setting, but, ah, certainly older infants and, and toddlers, ah, use of antibiotics for bacterial overgrowth, ah, at times, ah. Ah, children who seem to have acid related problems, um, acid blocking medications, and then, uh, promotility or anti-motility agents that have enhance absorption, but I, I think the, the. Principles that were really hit home, the data that you showed with the advantages of breast milk and, uh, advancing feeds, introducing solids, uh, when you can, I think that those are, are the most helpful, uh, things that we found at our program as well. So, to touch on probiotics, I think a lot of people want to know about that. I see as milk as a prebiotic, but probiotics and the role of, um, antibiotics and, and, and do you have a routine, or is this a patient. Uh, you do it per patient. Yeah, I think it's, ah, really, um, uh, based, ah, um, on individual patients. Ah, we will do, uh, uh, uh, lactulose breath hydrogen testing for children, for some children, so, uh, that we have high, uh, index of suspicion of symptoms of, uh, bacterial overgrowth. Others, um, uh, who we know have overgrowth or have demonstrated that previously when those symptoms, uh, recur, uh, then I think we'll, we'll think about probiotic, antibiotic, uh. Um, uh, combinations. I also think that, um, a lot of, a lot of this tend tends to be, uh, uh, you know, uh, on the, um, uh, more, uh. Ah, what, what has worked for that patient, ah, in the past and, ah, whether or not that they've had, ah, recent episodes of, ah, systemic antibiotics for Lyme infection in terms of, of what, what to use and, and when to use it. So again, one of these very individualized aspects of the care for the intestinal failure patients. So, are you using probiotics and antibiotics at the same time, or are you cycling them off each other, or what are you doing? Right, sorry, so to clarify, not, not, not the, uh, same week per se, but we would cycle one week on a probiotic followed by antibiotic. Usually available over the counter Culturelle. It's something that we can get through our typically reimbursed by our our state Medicaid algorithm of antibiotics that you use. Oftentimes starting with Flagyl, we do tend to use rifax and then we've not been a center. Ah, I know some centers will periodically endoscope. Culture, if you will, enteric fluid, I think to me that's Varies a lot based on how far down you are in terms of what you'll grow out and the concentration. So we've tended to, to go with, uh, Flagyl rifaximin, uh, neomycin, um, and a whole host of other, um, antibiotics typically aimed at anaerobic or gram-negative organisms. You know, uh, maybe we have a little controversy here. Uh, I, um, uh, the older I get, and I'm pretty old, um, uh, the more I recommend, uh, prebiotics and the less I recommend antibiotics. Um, I, um, Uh, I think that, um, we, uh, if you really come right down to it, almost all of our patients who have, um, a who've had a substantial resection have lost distal bowel and have lack an ileocecal valve have, uh, an element of, uh, of small bowel, if you want to call it. Contamination with uh with konic chlora, and, uh, I think what we want to do is encourage the right kind of, of flora and discourage the wrong kind of flora. I think we need to discourage, uh, putrefactive bacteria such as E. coli, Clubsella, and the like, and we want to encourage the anaerobes. So if we use too many antibiotics, and the ones that have customarily found favor have been those that have a relatively limited spectrum, those that that cover anaerobes, uh, such as flag, uh, such as metronidazole, um, uh, uh, uh, nitazoxidide, um, rifaximin has a bit broader spectrum because it will knock off both anaerobes and aerobes, but, um. The you'll be killing the bacteria that that you really want to be present and to break down your your starches into um into uh and your oligosaccharides into uh butyric acid, which is probably the most valuable of the fatty acids that we have. So, um, so if a patient is thriving, uh, I almost never use an antibiotic. I will use an antibiotic if we've seen de lactic acidosis. I will use an antibiotic if we've seen hyperaminemia, um, and I will see, and I will use an antibiotic in an older child who seems to be no longer thriving on, um, on a, a caloric intake that was in, uh, uh, producing growth. Um, weeks before, and if I do use an antibiotic, it'll be for a finite period of time, maybe 2 to 3 weeks, and if we see an improved growth velocity and increased velocity of weight gain, then I may cycle that antibiotic. If not, then I abandon the antibiotic completely. So I, I do use antibiotics, but much more selectively than I used to, and I think to draw on a point that Jeff made, but I don't know if it came across the way I wanted to, is that breast milk has non-nutrient oligosaccharides, meaning that the body, the 2FLs, 3 FLs are not actually a nutrient source to the human, but what they are coming to become known for is that they affect the microflora and dysbiosis. That we see in our intestinal failure patients is profound, and we, I think, further that dysbiosis by H2 blockers and antibiotics and the things we do, and we just don't know enough about how that's affecting the adaptive process, and I think I look forward to the next couple of years of looking at the fact that breast milk has secretor status. So if you don't know, your donor pool, 80% will have a secretor factor. Make a 2FL, which is immunomodulatory and and so when you're giving, you have a mom, you don't know her secreta status, you just don't know the moms that don't make 2FL that make 3FL may have actually different immunomodulation but promotility issues. And so I think non-nutrient sources, the dysbiosis, how the bacteria are affected by what we feed, and how the bacteria are telling the bowel to adapt are all things that I really think. We're going to learn about in the next 5 years and I don't know if anyone else wants to chime in, but I'm excited that I hope that industry and people who are providing us formulations realize that we're not just providing a nutrient source to grow, but it's an immunomodulatory thing that we're doing for these patients that is so important and I think we just need to develop better formulas to feed and to treat these patients than we currently have. Any comments out there? So, so, I, I just wanted some clarification. Make this, make this basic for me. So, antibiotics, are you talking about, you're talking about maintenance therapy of probiotics? Are you talking about, or you said that you don't use antibiotics as much anymore. For, well, first of all, I mean, and I want to get everyone else's opinion on this cause you said it's controversial, yet I see everybody nodding their heads. So, I want to know if there's anyone out there who disagrees with what you said. But I need to understand first what you said before I ask this. OK. So are you saying, I, I believe in prebiotics, OK, OK, and, uh, the, the oligosaccharides, I think are extraordinarily valuable because they, they induce a more healthful flora. OK, um, and so this is in, this is in everybody, in everyone, OK. It's not I was getting breast milk. There's no, these oligosaccharides and breast milk are not in formulas. There's a unique aspect of breast milk where there are non-nutrients, oligosaccharides that are present that are not being utilized for current formulas that you give in your NICU. Um-hum. And so, those, those formulations include oligos that are directly changing the microflora in a manner which we predict is going to be beneficial. OK. And I, I customarily don't recommend probiotics, um, based, In part because of individual case reports of patients who've had central lines who've developed anaerobic bloodstream infections. I don't believe that they occurred through translocation. If you believe in translocation, I think most of those actually occurred through direct line contamination. Um, I know. The pit was a center where there was a flurry of activity years ago trying to better understand translocation and generally the surgical definition of translocation is creating a surgical short bowel syndrome in an animal model, um, and Uh, and, um, and then finding bacteria in mesenteric lymph nodes, which I'm not sure has ever been replicated in a human being, um, but, um, the What we have found in some of our recent data, Conrad was actually a senior author in this paper where one of our fellows actually looked at biomarkers for bloodstream infections, and one of them was Flagellan, and uh and what what we found was that probably 2/3 of our bloodstream infections were seen in patients who were on. Prophylactic Flagyl. Why? Because we're knocking out anaerobes and we're facilitating, uh, aerobic overgrowth and and and uh presumably, uh, these patients are experiencing translocation. So there. Does anyone here routinely keep their patients on antibiotics at some interval, either, either continuous or interval? I do, um, especially those patients who've had, um, uh, multiple bacterial infections. Um, I try to Multiple bacterial infections of the. In their, in their, in their central line. OK. In their central line. Routinely, at the beginning, you get a patient. No. Do they get, what, what, you have to have an infection to start the. Yes, you at least have to have one infection before I will start. This is not part of your maintenance therapy. No. For, for, for prevention. You do it as a treatment. If they had a problem. Yeah. Then you start it as a prevention method. Yes. OK. I will. Um, OK. So Lyme infections is your only indication. I will also, in some instances with cholestasis, um, some patients I may be seeing early on that may be jaundiced, um, if I have any concern that maybe endotoxemia is playing a role in their, um, cholestasis, I may treat them with antibiotics rudely. Um, I, I typically start with Flagyl. I may use, um, I've used Bactrim before. I've also used, no, I never continuously. I try to give them a cycle. So, two weeks, uh-huh, maybe two weeks after. Flagyl is the wrong choice. OK. Because that's OK, some controversy. I think, Flagyl is absolutely the wrong choice. It has a limited spectrum. It knocks off your, your anaerobes and facilitates the growth of what do you use if you had to use it, if you have a patient with Lyme, well, let me ask you first. Patient with Lyme infection, I treat the Lyme first. You get treated because we used an ethanol. I seldom use antibiotics anymore, uh, but if I were desperate, I might do selective decontamination. I might use a non-absorbable amino glycoside. Uh, such as Tobramycin and, uh, Colistin, uh, those, that was the old PIP method, right? uh, rifaximin may have a role, uh, but it has not been well studied in bacterial overgrowth, and we really don't know the appropriate dose to give it bacterial overgrowth, and there's no stable suspension of rifaximin. Um, I actually had. Approached one of the the company that that makes rifaximin to do an investigator initiated study and because they couldn't guarantee me that their suspension was stable, I I didn't do the study. So what I want to echo back and see if I'm hearing you correctly. I'm hearing. That in, in a patient that, uh, first of all, let me try to back up. Lyme infections we heard, maybe cholestasis. Is that agreed upon that if we were to use antibiotics, that would be the most common reason why? So, I, I, I, my, my thought is that I'm not using it to prevent bacterial infection, actually. I'm using it to promote motility. Because when you decrease overgrowth, which is what I'm trying to decrease, then I'm hoping to improve the quality of the mucosa in the bowel, so decrease inflammation, and then increase motility and tolerance and absorption. That's what I would, that's my goal. So if I cycle it, I cycle it because I'm having issues with growth. I'm having issues with feeding intolerance, but for infection, that would be the bottom line or if I know that this patient does have other symptoms or has a documented overgrowth. So you have a patient that you're treating. Uh, who is not gaining adequate weight, you're feeling that they're malabsorbing, uh, through your workup, that patient you would consider starting on? I would, I would do metronidazole. So, I would, I would cycle or I would do, I mean, I mean, I know that it, it, you know, like it's, we're talking about controversy. It might be the wrong choice, but, I mean, I think that when I do decrease anaerobics, that I might promote, you know, some amount of, uh, uh, uh, at least because when, You look at the if you culture most of the bacteria we do get when you do qualitative culture anaerobes in terms of those that are going to be the cause for overgrowth. So that's the reason why now we've heard Lyme infections, malabsorption, cholestasis, question of not, antibiotics, no antibiotics, and then which one do we use, and then probiotics. In the virtual audience, and by the way, you guys have been so polite, and that's great, but we don't like that. So please interrupt us. Don't wait for us to call on you, yell and call, we can hear you, so say something if you disagree. Is there anyone out there that absolutely has a point they want to make that they disagree with what's been said, otherwise I'm going to call on someone. Well, no, this is Simon. I think what the discussion points out is that the lack of knowledge we have. We know that the microbiome is important. We have no idea how it, um, reflects what we normally see in, in adults and even less what we normally see in children. So I tend to do it on the basis of what I see clinically. It, um, if I'm growing a lot of gram negatives from the duodenum quantitatively, or if I've got cholestasis, we know LPS is bad in the portal system for for liver disease, then I might try a non-absorbable amino glycoside. If I've got a kid who's sudden, you know, changed in their stool pattern, they're getting extremely distended, they've got frothy diarrhea, it's more quantitative, or they've got the lactic acidosis, I'll give them Flagyl, um, you know, some patients do better with, with, um, long term, um, oral amino glycosides or rifaximin. If that works for them, then I'll use that. I like the idea of prebiotics. I think probiotics, we're not giving the right organisms. I, I think just because we can give Lactobacillus doesn't really mean it's the best thing for the whole of the bowel. Um, but I, I think what we really need is we need more information because we have to understand how the microbiome changes, and I suspect very much that the reason our, our patients seem to advance well once we can get them onto solid food is because there's something, um, More physiological about the exposure to complex proteins, to complex oligosaccharides, but we don't, we can't bring it all the way down to a single thing at this stage because we just don't know enough. I think I'd like to echo what Simon said as well as Sam's philosophy. I think that Uh, I bring this up. One of the things that I'd like to tell patients is, uh, is, uh, antibiotic use, probiotic use, um, uh, changing the, the microflora is, I, I sort of see it as analogous to the introduction of snakehead carp to to American waterways, or the idea of introducing a new species to a complex ecosystem that you're not sure what's going to happen. You're going to have changes that you evoke. Some may be positive, some may be negative. We don't. have the information or the knowledge about the interactions of the, the, the, the ecosystem of the microflora to, to really, um, to really be able to make good or smart decisions. So I tend to utilize uh uh mostly antibiotics and not probiotics, um, only when I'm forced to, um, with uh um uh d lactic acidosis, for example, uh, I think Simon made a good point, whenever you have a stalling of feeds. When there's abdominal distension, decreased abdominal gas, uh, I, I tend to tend to use Flagyl, although I do tend to agree with Sam that there can be disadvantages using Flagyl. The reason to use the metronidazole or anaerobic coverage is because they tend to be the gas producers. They can't be the ones that cause lactic acidosis, but, but it, it's uh it is individualized. We know that metronidazole doesn't work for everyone. And especially in some of our kids with the lactic acidosis, it seems like there's very, um, there are very um uh specific antibiotics that seem to, to work with them, and you have to sort of uh try to find the best one. We generally try not to cycle, we try to use it once and then see how long it goes before, or if it happens again, sometimes we don't have to cycle at all, but if we're, we're left to cycle, we try to cycle at the, the longest intervals uh possible. And then finally, the point about probiotics, I, I don't think I'm. Unnecessarily. I think probiotics in different gastrological conditions can be somewhat helpful. I'm not a big believer in translocation. I think the early Pittsburgh data from years ago doesn't necessarily highlight the sentiments of of what we practice now. I worry about probiotics getting in central lines through external contamination. Um, uh, even more so than translocation. And I know that some of these lactobacillus species are extremely hard to clear. Um, and, um, when, uh, these species get in central lines and they can't, um, clear, then you're left with pulling a line and you come back to the whole central line issues. Uh, it, it's made us a little bit nervous. We have an ID ID, uh, A physician here who once was able to establish a blood infection with the same genotype as the lactobacillus that was being given as a probiotic. And I think that sort of all sort of turned us away from probiotics of all kids have central lines. So, I mean, I, I think that it's a, uh, we only use antibiotics um when um when pushed to, we try not to use probiotics when kids have central lines, and um. And for better or worse, I do think that um uh we uh we do think about the the prebiotic and the, the, the use of uh of uh prebiotics um more so than uh than the other two supplements. So Mike, um, Mike, we have about 15 minutes left. So I think this was a great conversation. I wanna, let's change it a little bit another really challenging thing that we have is hypermotility. So, and that's a huge, I think, problem that we have in intestinal failure. So. Uh, now I got Jeff on the screen. What do you do with the kid that's hyper modal? What's your management of that? Hypermodal, hypermodal, it doesn't seem like there's any, uh, there's any normal motility in these, uh, uh, these kids. I mean, I think the first thing that we, we, um, uh, we think about in kids with increased output is, are we trying to overfeed? Are we overtaxing the gut? The, the most, uh, important, um, uh, component, a lot of kids with, uh, at least anatomical shortcut syndrome, are, are we, um, uh, uh. Providing uh the elements for an osmotic diarrhea uh to occur, and, and are we pushing too hard or too fast? I mean, that's always the the first thing whenever, whenever there is uh one of the things that we uh push for um. And again, it's sort of the art of surgery. I always like to think that we're uh conservatively aggressive, if that makes any sense with regard to surgery and with regard to reastomosing uh colon, because when you have colon that's involved, that will also help uh with uh with output. And when there's colon involved, using these uh anti-motility drugs, such as loperamide, um, uh, do become helpful, and they, I think it, uh, other ways that we, uh, other things that we do to decrease, um. Uh, uh, uh, output, high output would be, um, the use of the soluble fibers as well. Um, we have tried, uh, at certain times, things like, uh, octreotide. Um, uh, I've personally not found it, um, very useful. I worry about chronic octreotide use with with growth hormone suppression, trying to, um, trying to, uh, get the kids to gain weight and grow. Uh, we're giving them an anti, uh, something like treotide, uh doesn't seem to make sense. Also, the side effect profile, uh makes me nervous. If it would work, or if it does work in individual case, I'm not going to necessarily, uh, uh, stop it. Um, there are people that, um, uh, and, and or patients that have, uh, a lot of gastric output. Um, that might be a time to use a proton pump inhibitor to see if you can decrease some gastric secretions. But again, every time you use one of these medications, it's, it's, um, you have to balance it with the potential risk, um, uh, uh, again, of, of, of the medication itself. So there are a couple of options that you can use to both decrease output from hyper osmo uh, uh, uh, solutions in the gut or osmolar diarrhea, but also try to affect the secretory components as well. It's it's a variety. That's good. Conrad has a good observation that he's had with inflammation. He alluded to it. Maybe he can talk about inflammation and hypermotility. I mean, in some of these kids, I mean there is documented inflammation and when you do endoscopies, you can find it, and it usually seems to be an acute. Chronic when there seems to be issues because when you do use some anti-inflammatory agents, some of the 5SA products, it seems to have an impact. Sometimes, depending on where the position of the inflamed region is, using steroid-based enemas might also be helpful. Has anyone else had, have any experience with anti-inflammatories and hypermotility? I find it really helpful in the challenging Hirschsprung's patient that has a lot of dysbiosis and the frequency of stools can be really, really challenging, and that has gotten us through on many a patient that was otherwise not well managed with the other things mentioned. So, this is a patient on TPN. No, no, no. So, a patient at home on Hirschprung's that may have had a viral infection. She may be 89 years old. OK. And is now stealing 12 times a day, uh, and getting it under control and not responding to cycling of antibiotics or, um, other, uh, prebiotics or formulas, and Conrad has, um, successfully managed some of these kids with, um, anti-inflammatories and ASAs in the long term with, with, Remarkable success, but again, that's anecdotal in, in few patients. But certainly I think those are the, those are the kids I'm most worried about. I'm hardest to manage the hyper motor kids that want to eat. They are ravishing POs, and they, and they either their stoma or their stool output is, is, is fairly voluminous. Does cholestyramine work? Cholestyramine. Anyone have a comment on cholestyramine? Sam, Sam, I know does. I have comments, but I. I, uh, like to avoid it as much as possible, um, I think, um, the doses that are effective in, um, in firming up the stool are usually doses that, uh, will bind nutrients, um, fat soluble vitamins and fats. Um, and there's always a slight risk for, um, hyperchloremic acidosis in those, those patients who have it, and in fact there, there's a risk for bezos, cholestyramine bezos, so I tend not to use it now. I've encountered patients who were put on almost homeopathic doses, uh, and whose parents and, um, physicians believed, um, had better looking stools. But I'm not sure that the stool volume actually declined in that group of patients, so, um, I usually don't, um, uh, uh, uh, contradict or, uh, or refute anything that they're, they're said to me, uh, uh, with, uh, for a second opinion, but, um, but I, I don't initiate it myself. Anyone else out there like to use cholestyramine or Actigall or anything that they want to talk about? I've never found them useful. That's a far more succinct way of saying it. I think, I think we're in agreement there. Yeah, and actually, Ashley, another thing to comment on, you brought up Aigal, um, uh, especially in, in a child with a very short gut, it can, it can also contribute to diarrhea because of the cosmo component, and really with, uh, um, uh, no real, uh, um, benefit with regard to preventing cholestasis, especially, you know, again, with the real shortgut, I think that that's one of the things that we, uh, Uh, combat all the time is the appropriate use of, uh, something like that to golf. Um, you know, one could even argue, is it, is it useful, um, To begin with, to prevent cholestasis or to treat cholestasis, but, but definitely whenever the bowel is short, not connected, it will contribute to the diarrhea. It was a question on the use of pancreatic enzymes. Yeah, so, so, pancreatic enzymes, um, Uh, I guess that conversation, I'm going to bleed into some of the cystic fibrosis patients as well because they're the ones that we tend to use them on as well. Obviously the pancreatic enzymes are not physiologic in humans until they're probably more along the line of 567 months of age. Whether that's true or not is still, I guess, maybe open to debate. Our colleagues that take care of our kids with CF that have had complications like. Maconium Emilius like to resume those pancreatic enzymes very early, and my experience has been with that is that they believe there's better growth. I don't know that I know that or not. I've been told that and it's probably true. I've worried about pancreatic enzymes and stuff in dismodal areas of bowel, especially with stomas, and I think I've seen more than one. Stricture or stoma problem that I relate to enzymes and it's not that they give a problem in otherwise normally functioning bowel, but if you have areas of stenosis and dysmotility and it sits there, I do think they have a potential risk for harm. So I use, I use them as I am told by their protocols, but I still have concerns about them. But I Wouldn't make them stop per se, and I don't use them routinely in intestinal. I agree with Mike. I think that we have to remember physiologically the only pancreatic enzyme that's present in adult quantities are the proteases in the young infant. The the diastases, the amylases don't appear until Somewhere between 6 and 12 months of age, and then lipase doesn't reach adult levels until the end of the first year of life. So, so it, it, I, I tend not to use them. Um, we did do a study years ago, uh, looking specifically at immunoreactive trypsinogen in short gut patients, and in fact because they don't have enough enterokkinase, their trypsinogen levels are very high. Um, but if you do a, um, a formal pancreatic stimulation, you will see that, that proteases, uh, can do, do appear, um, the, um, so I think that, that, uh, it's, um, uh, again, it's a, it's a rather, uh, uh, problematic issue, and I, I think that, um, if you see a hydrosinogen. You know, and the patient's not growing and the patient's older, you might give a trial of pancreatic enzyme, but on the other hand, if, uh, the patient is an infant, I almost never use, uh, pancreatic enzymes. The other problem with pancreatic enzymes in a short gut is that they go through before they've even released and you get the. Yeah, good point. Uh, there was a question that relates to this regarding. Yeah, the, uh, we're now we're talking about a newborn who has a stoma, and the high stoma output question here is what is an acceptable amount that allows you to continue to, what's, uh, I guess, is there a succinct way that we can address the concern of feed advancements and high stoma output? So I would make two comments. One is I don't think there is an upper number that is, that is hard, fast. I think that we have many patients with 40 and 50 cc. Per kilo out of a stoma that will continue to feed, I think it's based on their electrolyte profile. Certainly you don't want them acidotic, and if the CO2s are dropping in the teens and stuff and you're maximizing acetate and whatnot, I think you've reached your limit, but that's not the volume limit. That's because the electrolytes and the acidosis is driving you. I feel like sometimes when Become very high. The knee jerk reaction is to either stop or cut feeds back way back, and I think that if you are using a number that a nurse can call you on that's directly changing your ability to feed the kids, you end up with a profile of kids receiving variable amounts of feeds over a longer period of time, which is very detrimental to a program that's trying to wean them from that. Knee jerk reactions to volume of output unless they're otherwise sick and showing signs of illness, acidosis, and fluent electrolytes should be made, I think, not as a knee jerk reaction, but as a more thoughtful overview of the pattern that the child is doing. So I never give a full number because once that number is reached, it begets a decision to be made which I don't think takes everything else into account. I, I agree, definitely. I think the stoma output or the stool output for that matter is, is more relevant in guiding your fluid and electrolyte replacement than it is in. Making decisions about whether or not you need to stop feeds or or decrease feeds, and we, we really have a very short period of time, but I think one benefit that that some of the new, the new papers on Gadds and stuff that came out and people ask us all the time about growth factors in GOP too, I think it's important just to mention, maybe Sam will mention this, is, is that it is profoundly interesting to. Patients who've received therapies like GLP-2 that their stomal output do dramatically go down and that there's a benefit in fluid and electrolytes probably seen from that whether that gives a sustainable benefit and whether the use of that in kids is indicated is by far not been determined, but I think fluid and electrolyte management is potentially a role of therapeutics. What do you think, Sam? Yeah, I think. Uh, the GLP-2 analog, um, I'm currently, uh, one of the lead investigators in a multi-center study. I know Rob, uh, Jeff, and And, uh, Simon, I also have, uh, patients whom they've enrolled, and Valerie has, uh, has enrolled some patients in this pediatric study, so the data are not out yet from that study, but the adult studies suggests that it is indeed beneficial. It can reduce in the vast majority of patients, in at least 60 or 70% of patients, it can reduce, um, uh, fecal output such that you can reduce TPN by about 20%. And in about 20% of patients, uh, if in the extension study, it was shown to totally emancipate them from TPN, um, so it, it really does seem to be beneficial, uh, but then there's another group of patients who, who do fine while they're on it, but then. Then regress when they when they come off. So I think the jury is still out on it, but there is some promise with that agent. Yeah, I think, I think that, you know, just basically says, uh, we have a lot to do, um, with this field. I think there's a lot of things that need to happen in studies, and I believe personally that studies that, oh, wait till child, children have late intestinal failure are not likely to give us the insight that we need, uh, for this and that multi-institutional trials and, and getting paid. In areas where we can follow them, not only provides really good outcomes and better care for them today, but provide us insight into what we really probably need to be doing in the next 5 to 10 years because we've made major advancements in this field in the last 5 to 6 years that I don't know are fully recognized and I think the trajectory is such that we're going to see a remarkably different treatment. Paradigm for these patients um uh in a very short time period so I think this is an exciting field and I'm really grateful to the fact that we had so much participation of our colleagues around the country and the UK and people were able to interact and I hope that people found this as uh informative and and worth your morning to spend with us. I I truly enjoyed it. I think this was fantastic. And, um, we have about a minute left and I just don't know if anyone has any last minute, uh, things that they weren't, that weren't discussed that they want to ask about. Uh, we have about a minute left. Any, anyone here have any burning desire to talk about anything? I mean, I think the issue is that when these patients are on long term TPN, they have to be monitored. It's not just looking at growth, but measuring their weight. And measuring appropriately length, but also looking at the micronutrient status, I think that's very key. I don't know if that was brought up at all, but it's not just looking at length and weight, but making sure when we talk about multifactorial issues that impact on neurodevelopmental or cognitive outcome, those are definitely things that need to be monitored over time. And because it also impacts bone health, which people don't usually think about, so all of those need to be part of the comprehensive management of these patients. It's a great summary point. Anyone else have anything?