Hello, welcome everyone to this luncheon session. Hopefully you get a quick meal while you learn something as well, right? I'm here, I'm Dr. Bincy Abraham, Professor of Clinical Medicine at Houston Methodist Hospital. And I'm here with my colleague who used to be in Houston with me a few years back, Dr. Monree Kaur. And she's in Mayo Clinic. And she'll be talking to you about acute severe UC. And I'll start with how to manage your severe hospitalized Crohn's disease patient. And we did leave some time in the end for some questions too, so we're happy to answer them as well. My disclosures, objectives, I'll talk about kind of assessment of disease activity, really a management algorithm that we should consider looking into. And also helping prevent and manage complications for patients that are in the hospital with Crohn's disease. So this is like the bane of my existence. We get a GI consult. And how many of you are a gastroenterologist? Okay. How many of you here are medicine providers, residents, hospitalists? Okay, that's just a few. Okay, good. So this is actually the bane of my existence when we get a GI consult and they say, oh, we have a Crohn's patient for you, but to help you out, we already put them on steroids. I'm like, no, no, thank you. Can you take them off that steroid quickly or let me assess the patient first? And so I'm always telling them, and I'm also telling my GI fellows too, like don't start our patients on steroids just because they're coming in the hospital with Crohn's flare. Figure out why they're there and what type of flare it is. So always check and make sure there's no infection. You want to rule out infection, C. diff, or other enteric infections. Also make sure there's no abscess or phlegmon or perforation. You don't want to be treating an abscess with more steroids. You also want to make sure they don't have fistulizing disease and that's not the reason they came in for their Crohn's disease as well. Because if they are coming in with a phlegmon or abscess or a fistula, what you don't want to do is treat them with steroids because it's going to prevent them from healing and also make potentially matters worse as well. So you want to make sure the steroids are removed. They've already been on it or the ER decided to go ahead and give them a dose of steroids. Now I also see that our patients end up getting a high dose steroids and like a COPD protocol of like 120 milligrams cube, 6 hours or 8 hours when they don't need that much. For our IBD patients, 40 to 60 milligrams, if they need the steroids, let's say they have them coming in with an obstruction but we're not sure if it's completely fibrotic or a combined inflammatory fibrotic, you know, stenosis is causing their obstruction. Sure, that's the time to give them steroids to see if the steroids can help improve that initial inflammation and improve that obstruction. However, 40 to 60 milligrams max daily is enough. More than that, there's no increase in efficacy and there's really more side effects to it. So keep that in mind too. They don't need COPD protocol steroids, okay? Now other aspects and you can see here there's a lot of layers to this. Diet and nutrition is very important. We need to feed our patients if at all possible. Often see again that patients are put NPO right after get go from the ER or the hospital has put them on NPO waiting for us to make a decision on their care. True, that's fine if they're just immediately in the emergency room waiting to make sure that their CT scan, make sure there's no perforation, make sure we don't need to get a surgeon on call to see them. But often if they're coming with a flare just inflammatory or it's okay to feed them, let them eat because often they may actually already be malnutrition or they may have been on NPO for quite some time or the patient may have come in thinking they were starting to flare and really didn't eat for a day or two as well. And if you're considering and you need to consider putting them on a procedure for tomorrow, get colonoscopy, just put them on a clear liquid diet and you can start their bowel prep and so on and so forth. And in some patients, let's say they're coming in significant weight loss, you need to assess for malnutrition especially if it's someone you haven't seen before. They're getting admitted through the emergency room, coming with a flare and we're getting CT images, inflammation everywhere and their albumin comes down to 2.0 when you first see them. They're the ones who you need to start assessing early for parenteral nutrition as well. Lab work, of course you know the basics and usually those things are done in the emergency room but they often don't do inflammatory markers so it's always good to get the CEDRATE or CRP in those patients to assess just systemic inflammation. We know they're not specific for GI tract. We know they're not specific for Crohn's disease per se but if you see someone's CRP is through the roof and it could be 10 or 100 depending on your lab levels you know that maybe it's not just a general GI flare or their Crohn's flare, it could be an infection or something else terrible like a perforation has happened. So it's useful to get that systemic assessment in those patients. Of course Calprotectin is always useful if you have an in-house lab you can get that pretty quickly to assess mucosal inflammation in those patients as well. And the other things you can do especially if you see someone who's more been chronically ill, get some nutritional assessment especially those patients who have had ileal disease or have ileal stricture and get their B12 levels. Maybe they have a multifactorial anemia, it's not necessarily iron deficient anemia, they may have iron deficiency and B12 deficiency and other deficiencies contributing to their overall poor health, weaknesses, et cetera. So make sure you get their B12, folate and those patients who have significant diarrhea, especially in my Crohn's patient I tend to see a lot of zinc deficiency as well. So it's always good to get those assessments and then optimize them. And if you actually end up seeing magnesium deficiency in the blood work that means they're severely magnesium deficient. These patients often will need IV magnesium infusions to optimize them and build up their reservoir because their reservoir is actually gone as well by that time. And of course you'll have patients coming in with pain and in the IBD world we generally try to avoid narcotic pain medicines for our patients. Mainly because from our old treat registry that was the old registry study from infliximab days where we found out that, you know, we thought oh gosh, infliximab and immunomodulators can increase the risk of infection, we need to follow these patients over time. And actually what we found was that narcotic pain medicines and steroids actually ended up increasing mortality and morbidity for our patients. It wasn't necessarily that original first biologic what everyone was scared of. So yes, it's important that we control our patients' pain. But we, and in the hospitals sometimes they're on narcotic pain medicines to get that initial pain under control. But we need to assess for these patients, see if we can get them off narcotics as soon as possible. Get your pain management providers involved to help you there. I in general do not prescribe any narcotic pain medicines for my patients as an outpatient at all in my practice. If they need pain medicines they are actually being followed by pain management specialists. And of course I always tell them that, you know, getting them off the, someone needs directions to come here. Okay, we made it, we can turn it off. I do the same thing with my Google Maps too, so it's good. So it's important to get them involved. And then also assess ways to get them off narcotics and use other pain meds, tricyclic antidepressants, low dose can actually help our patients with enteric nervous system pain. And I use that very often in our patients as well. And even our patients postoperatively, our surgeons use even IV acetaminophen to help control their pain and reduce narcotic requirements as well. And for patients who have more intra-abdominal process going on, get serial abdominal exams for those patients, imaging as needed. And if let's say they're on a therapy that you can optimize while they're in the hospital, maybe get them on from 5 to 10 milligram per kilogram infliximab dosing if it's on formula in the hospital. See if you can get them that medication. Often, and you'll see in my talk that I'm not going to be talking about which specific medicine you need to use in the hospital. Because in the hospitalized Crohn's patient, often you can't get a new medication approved and immediately started and get their induction therapy. We need to calm down their processes first and figure out a plan of care for outpatient management. So that's not going to be the bulk of my talk. I'll mention some of these medicines for specific cases as well. And thromboembolic disease is very prevalent especially in our patients as hospitalized with IBD flares. So they need to be initiated with thromboembolism prophylaxis early as soon as they get admitted. And I'll give you some information on that as well. And if you think a patient will need surgery, get your colorectal surgeons involved as soon as possible. Don't wait until they've already perforated or they have this absence. It's not getting better with antibiotic therapy, et cetera. Now leading to that, really it's multidisciplinary care. That's a key. So if you're seeing a complex Crohn's patient in the hospital, you're not alone. You shouldn't take care of them alone. Get everyone to help. Of course, radiology. And a key thing here is often our patients get a CT scan in the ER and they're getting admitted. The CT scan shows something. The question is, is that enough? Do we need to get a more specific protocol like a CT enterography or MR enterography? In some cases, our patients get multiple CT scans. But check with your radiologist first. Often I'll go by and see them or call them and they'll say, oh yeah, a CT enterography is not going to help us more than what you already know from this. So why put a patient through more radiation, more imaging, or an MR enterography if you're really not looking to distinguish between fibrotic versus inflammatory stenosis? So check with the radiologist. Sometimes they'll be able to tell you like, look, actually if you do this protocol, we'll be able to better delineate the disease. Or if it's fibrosis or this absence is better, then go ahead and order it. But enterography protocols have to drink a lot of the volume and contrast. Some of our patients, they're sick and in a flare, they can't actually tolerate that either. So keep that in mind. As I mentioned previously, get colorectal surgery involved. If they end up needing surgery, it's better to have it elective rather than emergent. And often they are the ones who initiate all that ostomy training for your patients as well. And of course, if you see that there is an infection, get infectious disease involved. Of course, we and Dr. Caron will talk about the CMV component of a patient with acute severe colitis. They need CMV treatment. It's good to have them on board as well for duration of therapy if they need IV versus oral in the transition part as well. And for patients with malnutrition, get the dieticians involved early. Often our patients with Crohn's disease, especially the ones that end up in the hospital, often have been avoiding certain foods in their diet, trying to minimize their symptoms. They're malnutritioned because they're not getting the right foods. They're typically on a, what I like to say, a chocolate or cake diet because it's, you know, no fiber, low residue. It tastes good. They can actually absorb all the sugar, but nothing else gets absorbed, right? They're not eating the fiber. They're not eating the fruits and vegetables and all the other good nutrition in as well. So get them involved. And that's, you know, I speak briefly about general nutrition, but often these patients may need concurrent parenteral nutrition or even enteral nutrition for actual Crohn's as well. Any pediatric GIs in the audience? Okay, not any at all? Okay, well, in the pediatric side of Crohn's disease, enteral nutrition is actually used very often. We have data that actually helps reduce inflammation there. So sometimes enteral nutrition may be needed. It's hard for us adults to stick with an enteral nutrition diet because we'd rather eat our hamburgers and cake, et cetera. But they can help with addition of enteral nutrition to improve the patient's malnutrition as well. And of course, getting the case managers involved early because if you have a complex patient, they'll need help with discharge planning. If they need TPN, if they need home health for fluids and IV antibiotics or TPN, they can help initiate that. We're not waiting until the last day when you think they're clinically ready for discharge to get all that. They get delayed from the hospital as well. And the other thing is if you're, let's say, working in a small hospital where there's not a lot of expertise, let's say from the surgery side or from whatever else side, sometimes you may need to transfer those patients. I'm not talking about the standard patient who comes in, I'm in a flare and they have some inflammatory disease. I'm talking about patients with multiple prior surgeries, having a complex phlegmon and abscess. And general surgeons typically want to operate right away when our good IBD specialized colorectal surgeons will hold off on operating, maximize their nutrition, consider diversion surgery rather than resecting this big old mass of inflammation to optimize their care. So consider transferring patients if you're in a smaller hospital without that expertise as well. Of course, you're aware of the indications for surgery in Crohn's disease. I'm not going to belabor that. But I will specifically talk about when to refer patients for fistula and perianal complications as well. And again, calling colorectal surgery knowledgeable in IBD. I actually emphasize this, even in centers where there are colorectal surgeons, some colorectal surgeons really like to focus primarily on colon cancer and resections. But if you have someone, again, with complex small bowel disease, sometimes you need that expertise for someone who's done that type of work as well. And even my colorectal surgeons, if I have a complex patient with more proximal small bowel disease, jejunal disease, they'll get our foregut surgeons involved and combine that multidisciplinary surgical management with the foregut surgeons and our colorectal surgeons so we can optimize that patient's surgical care as well. So very important to have that expertise, especially in very severe, really complex patients. Okay, moving on to perioperative IBD management, nutrition. Okay, very important. Especially a patient, let's say you've considered, you know, optimized their care, gotten them off steroids or on IV antibiotics for phlegmon or abscess or infection. Let's say they're having an obstruction, you need to get them to surgery. You've made that decision, the patient needs surgery. Well, key, you want to optimize their nutrition. Key here is making sure they're not anemic and make sure their albumin is good. So what we've seen is that if you have preoperative anemia, you have increased risk of postoperative sepsis, intra-abdominal sepsis after an ileoclonic resection for these patients. If you actually correct it preoperatively, it improves outcomes. You have less likelihood for intestinal obstruction, bleeding, even pulmonary disease afterwards. Intra-abdominal abscess, of course. Anastomotic leaks are reduced. Postoperative perforations are reduced. Now, I won't go into details of mechanism why. There could be multifactorial. There are less sick patients in general possibly or could the having enough blood flow and, you know, hemoglobin to help heal those cells after surgery could play a role as well, including pneumonias, even wound infection. So ideally, you want to correct their anemia preoperatively because postoperative transfusion, and you see increased mortality, increased morbidity from infections, ARDS, and even increases endoscopic and surgical Crohn's disease recurrence. So you want to avoid all of that. Again, nutrition-wise with albumin, you will see that if their albumin is low, less than 3 or 30 grams per liter increases all complications from sepsis to increasing inpatient stay. Less than, if it's even lower, less than 2.5 increases intra-abdominal sepsis after early chronic resection. And if it's less than 2, actually increases mortality from 10 to 65%, so very important to optimize that nutrition if possible. Okay, now how do we optimize them? Well, screen. Well, it's easy enough to check an albumin, but high-risk patients have low albumin levels. Or you've asked them about their weight loss, and you see that within six months or less, they've lost a significant amount of their body weight, or their BMI is super low. In those patients, you want to initiate TPN or enteral nutrition as early as possible to reduce that inflammatory burden and those complications we discussed. If possible, you'd want to give them enteral nutrition if they can maintain their energy and protein requirements by enteral nutrition alone. But you may need to add on parenteral nutrition for these patients, especially if they're not able to absorb all their nutrition through enteral nutrition alone. Now, in some cases, we work with our colorectal surgeons to delay their IBD surgery until they get enough parenteral nutrition or other nutrition to improve their albumin so they are better off for surgery. And often, we can do this just quickly as parenteral nutrition for a few days before they go for surgery. But in some of those really severely malnutrition patients, sometimes we may need to get them on TPN bowel rest for a few weeks even, and then get them to surgery. And we've actually seen better outcomes, even if we had to delay surgery for those patients by getting their albumin higher. There's really weak evidence to use IV albumin. We just need to get their nutrition so it's not really a problem with their liver, not making albumin, it's really that they need the albumin from a nutritional standpoint. And for patients that have strictures, they have presonotic dilation, they sometimes need to be on bowel rest to reduce that presonotic dilation so that the surgeons may be able to do a primary reanastomosis rather than a diverting, like stoma first, and then reanastomosis later. Sometimes that can help just using parental nutrition alone. And postoperatively, you want to get them on oral feeds as soon as possible, ideally within 24 hours of surgery, because that's been associated with improved outcomes. And usually our surgeons are more involved with that, but again, we can encourage our patients to eat as soon as they see gas or, you know, have a bowel movement, but often just passing gas would get them started. Perioperatively, medications. Okay, steroids, we know, bad, okay? If you don't remember anything from this, steroids, bad, perioperatively, avoid them if at all possible. If they're on corticosteroids prior to surgery, there's increased risk of surgical site infections, deep space infections, where you're seeing those intraabdominal abscesses, especially anastomotic leakage, even in those with low-dose steroids. Topical steroids like budesonide may be okay. We don't have a lot of studies looking at them, but there's no systemic absorption. In my patients who have been on those short-term, I haven't seen complications post-surgically as well. So you want to limit the steroids exposure perioperatively and reduce intraoperative stress dose if they've been on steroids, and we can get them off as quickly as possible. But after surgery, you want to taper them as soon as possible. In some cases where you've just started them just two or three days before surgery, you may be able to not have to taper them off, just get them off completely post-surgery. But if they had been on a prolonged course of steroids and you try to get them to the lowest dose possible, they're still on it, needing it post-surgery, then taper them off quickly. Because you don't need the steroids for the anti-inflammatory effect. The surgery took care of that. Now it's more of protect the adrenal glands here. And if they're on steroids, generally our surgeons will try not to do a reanastomosis. They would do a diverting surgery first. Then once they've healed up off steroids, then they'll do their reanastomosis down the line. It's safer because it will actually prevent those complications, anastomotic leaks, and so forth. As far as medications, what can we use or continue to use before they go for surgery? A very common question. Immunomodulators, hopefully we're not using a lot of that now in our practice, is actually okay. We haven't seen any post-operative adverse events from them. Small molecules, we have very limited data. So I don't have evidence to provide you to say, oh yeah, they do fine. The good thing is JAK inhibitors generally have a very short half-life. So typically if you stop it within a day, two to three days, it's out of their system. So we don't have to worry so much regarding that. The S1Ps, hopefully you don't have patients that have severe disease. And we don't use it in Crohn's anyway, so not an issue there. Biologics, actually when you looked at the first infliximab data, there's a lot of bias because these patients actually all came, really mostly came from the acute severe UC population where there was an increased risk of complications. However, all those patients were on, guess what, steroids in the hospital. So we know steroids are related to post-operative complications, but we actually started deciphering those patients, doing analysis away from patients that had been on steroids and a biologic. Only on a biologic, the data is actually looking more favorable, the biologics are actually okay, and actually preferred because what I don't want are patients to get off their therapy, their Crohn's starts flaring elsewhere, and then they're back to square one as well. And the Puccini trial, they had over 900 patients undergoing intra-abdominal surgery with anti-TNF exposure, no increased risk of infections or surgical site infections. And with their other therapies like Vito and more targeted IL-23s, I suspect that should not be an issue either. So don't delay surgery on these patients. Diverting ileostomy is not required for a Crohn's resection in the setting of preoperative biologic use. It may be for steroid exposure. And delaying surgery in severe cases may actually increase complications and mortality, so you don't want to delay surgery just to stop their biologic therapy. So multiseminary management after surgery. Of course, they're going to be seen by colorectal surgery. You want to prevent and monitor ileus. Resume their IBD medication as soon as possible. My thought is, my take on this is usually within two weeks after surgery, I get them restarted back on their therapy. Sometimes they may be in between their biologic doses because they have every eight-week, et cetera, dosing. But that's okay. They'll just get back when it's time. But there have been studies looking at metronidazole. Even up to one year can prevent post-operative recurrence. However, our patients may not always be able to tolerate being on metronidazole for a year. And I typically do the minimum dose 250 milligrams BID, but 500 BID would be more preferred. I try to get them on at least one month of metronidazole post-op to try to reduce that post-op recurrence. It helps bridge that gap between their follow-up in your clinic, getting them back on their appropriate therapy as well. If you have increased ostomy output, that's often an issue, we let their patients know it's expected. It's okay to use antidiarrheals, okay to use fiber supplements, and tell them that it can improve with time once your GI tract kind of gets situated with what's going on and what they need to do to absorb more. In rare instances, you may need to continue parenteral nutrition or IV fluids, or in some cases, growth hormone, GLP, to tetraglutide as well. Thromboembolism, very important here to know that our patients are at increased risk with IBD flare in the hospital. It's more so in UC than Crohn's, but it's still about a risk of 1.4% for anyone especially going for Crohn's surgery. We see the listed risk factors, of course, bleeding disorders, emergency surgery, malnutrition, et cetera, but having active inflammation, prolonged hospitalization, having elevated platelets, thrombocytosis, which we see when there's active inflammation or infection as well, and of course, reduced mobility, very important to assess these in our elderly patients as well. And specific operations like having a stoma or J-pouch increases that significantly. And laparoscopy is actually protective over open surgery. Hopefully, most of our surgeons are now doing really laparoscopic or even robotic surgery for patients now. So that helps protect you in one way or the patient in that sense as well. And postoperative time to a VTE may not actually be in a day or two. It can be up to 10, 11 days, so it's a mean time. So keep that in mind. If a patient's discharged from the hospital, they're calling in saying, I'm short of breath or having lower extreme edema, high urgency, get them to the emergency room, get some Doppler assessment or a CTP protocol for those patients. Don't delay because especially if they've had surgery, they are at the highest risk. And it can even be up to six weeks after discharge. So be on the lookout for those calls and educate your MAs or nurses who may triage these patients as well. So prophylaxis for these patients preoperatively and postoperatively, get them to ambulate as fast as possible, consider even medication prophylaxis for those high-risk patients postoperatively, especially those who are elderly or not moving around or needing to go to a nursing facility as well. As you can see here, there's actually a trend. The longer you've been in the hospital for your surgery, you're at the highest risk of getting a thromboembolic phenomenon. If you have same-day surgery, usually not as high compared to you've been in the hospital multiple days prior to your surgery. Perianal fistula management, I'll kind of finish up here. So you have simple fistulas. These patients that you see in the clinic or they call saying they have some bump and you can assess them, you can follow these patients in outpatient. Some of these patients that may need to be admitted or have multidisciplinary management with colorectal surgery and may need to get additional radiological testing or exam under anesthesia are the patients with complex fistulas, especially high interspenteric fistulas. They have multiple external openings or, of course, if they have an abscess, they need to be seen pretty quickly. I try to get my patients with a perianal abscess in conjunction with their fistulizing disease to the colorectal surgeon's office that same day if at all possible. I'm phoning them quickly saying, hey, can you get this patient in? If they can't, then they go to the emergency room because I don't want them to be delayed in their care, end up getting sepsis or further infections. So those are the patients that need to be assessed sooner than later. And as far as medication, you see the list of things here, but infliximab probably has the best evidence to this day. Of course, we've had some studies with betalizumab, and we don't have as much data on the new IL-23 inhibitors, but here anti-TNFs are the way to go for treating or fistulizing disease patients. And if they've failed anti-TNFs and you move on to anything else, essentially it's better than obviously no treatment at all. The key here, again, is please avoid steroids in your fistulizing patients. It can actually worsen the fistulizing disease, worsen drainage, prevent healing, and increase the surgical requirements as well. Antibiotics use as adjunctive treatment. I use it very quickly to add it on to their biologic or advanced therapy agent, but we know that, and metronidazole and ciprofloxacin has probably the best data. Once you stop the antibiotic, they're not on appropriate advanced therapy, their fistula can reopen. So use it in conjunction. The other medicines I've listed a bunch here, thiopurines may usually use that in conjunction with anti-TNF. Tacrolimus may be beneficial, cyclosporine, but high relapse with cyclosporine, methotrexate, there's some studies there. Don't use aminosylates, please, for fistulizing Crohn's disease. Hyperbaric oxygen treatment can be used as adjunct therapy if it's available for the patient as well. And telenobide, not so much. So in conclusion, for patients in the hospital with severe Crohn's disease, SS disease severity, use your exam imaging colonoscopy as needed. Close clinical monitoring, use multidisciplinary management. You're not alone. Don't treat these patients alone. Initiate and maximize therapies early, optimize nutrition, provide VT prophylaxis, and continue your Crohn's therapies preoperatively until that time of surgery, and get them restarted post-op in your high-risk patients. Thank you. Thank you, Dr. Abraham. That was excellent. My name is Manpreet Kaur. I am joining you from the Mayo Clinic in Arizona, and we'll be talking about acute severe ulcerative colitis, a fairly common inpatient indication. So what is acute severe ulcerative colitis? Really there are so many different clinical indices that you can use, but we all as physicians know our clinical experience and knowledge and expertise guides us. When you walk into a room, talk to the patient, you know when someone needs to be hospitalized for acute severe ulcerative colitis. So I wouldn't worry about getting into the semantics of whether or not they're having more than six bowel movements a day. If they've had a significant worsening of their symptoms, they're looking pale, their heart rate has gone up, and you've seen them before and they do not look like their usual self, trust your clinical judgment, hospitalize them. Let's try. We're going backwards. Okay. So what I always tell our fellows is when we're assessing patients, especially if this is a patient you're not familiar with for the first time, either in the hospital or in the ED, try and break it up into three different themes. One is the current, how's the weather today? The second is what's the climate overall? And the third is what are some other factors that will impact treatment decision making? So the patient today, what's going on with them in terms of what is their inflammatory burden, what do we know based on the data you have for that admission with regards to their disease extent and severity? And then looking at the overall disease trajectory, how often has this patient required hospitalizations? How often have they required corticosteroids? What has been their response to corticosteroids? What has been their response to prior therapies? Have they tried and failed an anti-TNF or were intolerant? And then finally, what are some disease-related complications or other coexisting conditions that will inform your choice of therapy? Overall nutritional status, are they anemic? And last but not least, I think it's so important for us to identify hurdles to access and insurance early on. If you have a patient that's not going to be able to follow up or be able to afford a biologic, that should immediately get us thinking of treatment options that will align with their discharge conditions. So what do we do when we see the patient hospitalization day one? I learned this very early on in my training that there are some themes that have withstood the test of time in terms of assessing disease severity, both for ulcerative colitis and Crohn's, but for ulcerative colitis specifically, serum albumin and a manual differential that gets you a band count. These are two markers of disease severity that in data that was published out of Cedars-Sinai showed independently were associated with the risk, they were predictive of risk of colectomy. When you combined the two in patients that had a serum albumin of less than 2.5, a band neutrophil count of more than 13%, almost 100% positive predictive association with colectomy at 90 days. So if you can, at least once when your patient is admitted, request a manual differential so you can get the band count. This is not reported with an automated differential. And when you're reviewing that patient's list of medications, there's really no benefit in continuing 5-ASA agents. And I would strongly encourage you to discontinue those medications. There can be a small subset of patients that have a paradoxic hypersensitivity-like reaction, and that may be contributing to the flare of their colitis. If they are on an anticholinergic agent, I would discontinue it, avoid opioids. And this is something I see happening not infrequently. You see a patient with a low albumin, and some well-meaning colleague will put this patient on TPN. But if they're able to tolerate an oral diet, I would urge you to avoid parenteral nutrition. You're just setting them up for another nidus for infection. There is really no benefit in keeping these patients NPO. If they can tolerate a diet, they should be encouraged to eat. And then the general themes. None of this will come as a surprise to you. Resuscitate with fluids. If this is a patient you're familiar with and you know they have ultra-diff colitis, imaging is consistent with it, it is reasonable for you to go ahead and start corticosteroids. There are differing opinions on whether you should wait for the results of a C. diff test before you start corticosteroids. I'll come to that in a minute. And really the main decision for you at this point would be how recent has their endoscopic assessment been. If it was at a time when they were not in the midst of this current flare, I would plan to repeat endoscopic assessment as early as possible. But before we get ahead of ourselves, this happens not infrequently because these patients are coming in with hematochezia. Again, a well-meaning hospitalist will avoid putting them on a low molecular weight heparin for DVT prophylaxis. Now, if there's one thing I hope we can convince you today, it is that our IBD patients, especially when they're in the hospital, need DVT prophylaxis. It cannot be with those squeezy things that massage your calves because these patients are at risk for cerebral venous sinus thrombosis as well. So it needs to be molecular or a pharmacologic prophylaxis. This is the most compelling data. This comes from the UK, from the General Research Practice Database. And this data is now 15 years old. They looked at about 13,000 IBD patients, compared them to 70,000 non-IBD controls. And you can see at baseline our patients with IBD have a higher risk for DVTs, but that risk is especially pronounced when they're in the midst of an IBD flare. I mean, we're talking about a hazard ratio of 8.4. That's significant. So please communicate, educate your hospitalist colleagues. If you have trainees that work with you, hematochezia is not a contraindication for pharmacologic prophylaxis for DVT. And then plan early endoscopy. How early is early? Well, ideally as soon as possible. But I wanted to share with you this data where the study defined outcomes of early. Here they defined early as within 72 hours of admission versus delayed flexible sigmoidoscopy. So why do we need an early flex sig for several reasons? Assessing disease severity endoscopically allows you the opportunity to get biopsies to rule out CMV and has been shown to improve outcomes. As you can see, patients that had early endoscopy, they were less likely to need IV corticosteroids. So that's in blue. They had a shorter length of stay and mean time to rescue therapy was also much lower. So how early? As soon as possible. It does not need to be a full colonoscopy. A flexible sigmoidoscopy will suffice. It does not need a bowel prep. You could either just do unprepped. If that is a very unpleasant idea to you, then consider a tap water enema. That's really adequate for most patients. And again, when you're doing the colonoscopy or the flex sig, you don't have to worry about, well, what score is this according to Mayo or UC endoscopic severity? Which, by the way, if you use probation, it can be added to your drop-down list, making it very, very easy so you don't have to remember what mild, moderate, severe looked like. But forget all of that. If you don't have that, you don't have probation, just describe what you're seeing. If you're seeing deep ulcers, if you're seeing ulcers with undermining at the edges, or if you're seeing large parts of the mucosa that have sloughed off like these, describe it. So that if you're handing over the care to a colleague, they recognize this is a patient with severe features on endoscopic assessment. So we all know what deep ulcers look like. We all know when there's extensive loss of mucosal layer. We may not know, okay, that's what technically you're supposed to describe. But you can see the extensive loss. Sometimes the mucosa is denuded enough. You actually see the underlying muscularis layer. If you see ulcers where the edges are overhanging and the ulcer base appears to be burrowing, those are these well-like ulcers. Or if with minimal insufflation or endoscope trauma you see these large abrasions, these are all signs of disease severity and predict worse outcomes. So it's very, very important to make that assessment early on, certainly within the first 72 hours. And we'll come to steroids and C. diff here in a minute. Why must we always check for C. diff for every patient that's hospitalized with a flare of ulcerative colitis? Well, because it's incredibly common, both as a marker of disease severity and as an exacerbating component to why this patient may be flaring in the first place. Having concomitant C. diff infection has been linked with increased risk of colectomy, increased length of stay, and, of course, increased in-hospital mortality. The data on the right are from Brazil. And what they were able to show very nicely was that there's actually a dose-related effect with regards to steroids and the risk of C. diff. Higher the dose of steroids, higher the risk of C. diff infection. And I'm sure most of you here will not be surprised to learn metronidazole is not effective, should not be an option. Vancomycin and fidexomycin, those really should be your first-line therapies in patients with C. diff infection in the setting of IBD. And if you're going with vancomycin and this is not the first time your patient has been diagnosed with C. diff, consider a prolonged taper. Because there are data that show a prolonged taper with vancomycin has been shown to decrease recurrence. So I do my own prolonged taper where I tell them take it four times a day for two weeks, then three times a day for two weeks, then two times a day for two weeks, and then once a day for two weeks. And sometimes I've even gone to every other day for two weeks. Is there a study that informs that approach? Not really. That's based on clinical judgment and experience. So what do you do? Do you wait until you've ruled out C. diff before you initiate corticosteroids? Well, the ACG guidelines actually encourage you to treat C. diff for 72 hours before escalating therapy. The Europeans have a slightly different take. It's fine to start steroids and treat C. diff simultaneously. I tend to follow that approach. There is an underlying inflammatory process that's perpetuating the C. diff infection and the C. diff infection is worsening the inflammatory process. If you treat one without the other, you will not see adequate results. So in my practice, I don't wait to rule out C. diff before starting the patient on IV corticosteroids. And if it is confirmed to be C. diff, initiate either fidaxomicin or vancomycin. What about CMV? So once you've done these biopsies, you get the results and your pathologist says, well, I see one, maybe two positive cells on immunohistostaining, but I don't see any inclusions. What do we do with that? Well, I'm sure it won't come as a surprise to you to know that nearly half of us in this room have been exposed to CMV, right? It would be unusual to not have positive serologies. So there is a high prevalence of latent infection in the general population. In patients with acute severe ulcerative colitis, about a third of them will have CMV in their colon biopsies. But when must we act upon it? Well, that information is on the left. If your pathologist reports inclusions on histology, that will usually trigger an immunohistochemical stain. And if you see more than five positive cells within a high-powered field. When it comes to PCR, there are no defined cutoff points for peripheral blood PCR. If it's more than 1,100, unless it's, you know, obviously positive. So there are studies that show if it's more than 1,100, about 80% positive predictive value, that their patient may have CMV colitis. The cutoff points are usually defined for tissue PCR. So if you're doing PCR on your colon biopsies, and that cutoff has been reported to be 250, however, has not been validated. So really our best bet to rule out CMV colitis remains biopsies. If there are inclusions on H&E staining, then immunohistochemical stains. If you see more than five CMV inclusions per high-powered field, and you have obviously a patient with acute severe ulcerative colitis, I would err on the side of caution and treat this with IV ganciclovir. So what about corticosteroids? I think Dr. Abraham mentioned it before. There is really no need to go for whopping doses because there's been no documented benefit in exceeding 0.8 to 1 milligrams per kilogram methylprednisolone equivalent. In my practice, we usually go with 20 milligrams IV Q8 hours, Q8 rather than TID because then that just gives you a better dosing throughout the 24-hour period. So do not hesitate to start DVT prophylaxis. Do not hesitate to proceed with an early endoscopic assessment. In my practice, I don't withhold corticosteroids while awaiting C. diff assay. And there's no benefit in exceeding 60 milligrams a day of solumetrol or methylprednisolone and equivalents. Once you've started your patient on steroids, the things you need to be monitoring for are has the frequency of blood in their stool decreased, fever, tachycardia, abdominal pain, et cetera. I wouldn't go more than 48 hours without tracking CRP albumin. And I should have added band count here. What should get your spidey senses tingling is if your patient suddenly is laying very still in bed, doesn't want to turn, and you have signs of guarding rigidity or just peritoneal irritation. If they went from having multiple bowel movements to suddenly nothing, a stat KUB, you want to make sure you're not missing a perforation or a toxic, evolving toxic megacolon. These are things that will be fairly evident to you as clinicians. So once you've started the patient on corticosteroids, I'll talk about how to have the conversation on day zero with where you think this is headed and then how to track that response for the first 72 hours. And you'll see a lot of similar themes emerge here. So these are data from a retrospective observational study from Edinburgh where they looked at all patients over a period of time that were admitted with acute severe ulcerative colitis. And they saw that of those patients, the ones that had a high CRP and had a low albumin and severe disease on endoscopy, if you gave them a point for each and if they scored a point each, there was a 3 out of 4 of those patients, nearly 75 to 80% of those patients did not respond to IV steroids. So the outcomes in this study were, were they able to leave the hospital with their colon? Or were they able to leave the hospital without needing rescue therapy, like with infliximab? So predicting colectomy-free and rescue therapy-free discharge. So again, there are some themes emerging, CRP, albumin, I would encourage you to include band neutrophil count as well in your assessment to predict likelihood of response. And this is helpful because it will inform your discussions with the patient so you can tell them what to expect. And if you, you will in all likelihood not proceed to rescue therapy without at least trying corticosteroids. So once you have a patient on IV corticosteroids, there's really no additional benefit beyond 72 hours. They will declare themselves within 72 hours as either responders or non-responders. And you can try and memorize this different combination of how many bowel movements, what the CRP cutoff is. But bottom line, if your patient still has nocturnal bowel movements, it still has a lot of incontinence, not because they have proctitis-related urgency, which I'm sure you can differentiate. But if your patient continues to have large volume bowel movements with a lot of blood in their stool and it has not decreased from when they came in, CRP has not decreased significantly from when they came in, is when by 72 hours, day 3, you should be thinking of plan B. So what is that plan B? Well, let's first talk about patients that do respond. So among responders, we typically recommend transitioning them to oral prednisone, 40 milligrams. If your hospital and your case management will let you, keep them in the hospital for at least one day while they're on oral steroids because there is that subset of patients that is dependent on intravenous steroids and will go right back to square one the minute you switch them to oral steroids. So if you can, keep the patient in the hospital for one additional day while they're on 40 milligrams of prednisone. And this is also a good time to be planning for what the prednisone is a bridge to, if they have not had their prebiologic testing to send that, if the patient needs outstanding vaccinations before they start biologic therapy to address those. And we will focus on the ones that do not respond to corticosteroids. What are our options? But broadly speaking, for most centers, there are really only three. The oldest and the best, in my opinion, infliximab, we now have some JAK inhibitors or surgery. I will cover cyclosporine, but I recognize it's not very widely used. So infliximab, we have seen a lot of case reports and data that 10 milligrams may be better than 5 milligrams. And I'll address that in a minute. For cyclosporine, the usual dose is about 2 to 4 milligrams per kilo, continuous infusions. It's laborious. It's nursing intensive. You will not be a favorite gastroenterologist with your nurses. I can tell you that right now. And there's really no benefit. There was a head-to-head comparison, open-label, and cyclosporine and infliximab were fairly equivalent. And then we'll talk about JAK inhibitors. What are the data for inpatient use of tofacitinib and upatacitinib? And surgery, when to consider it? So these are data from PREDICT-UC. This was a randomized controlled trial in multiple centers in Australia where they gave patients that were coming in with severe ulcerative colitis needing steroids, a one-time infusion of 5 milligrams per kilo or 10 milligrams per kilo. And then they assessed their response at day 7 and disappointingly did not see any difference. I say disappointingly because how wonderful would it be if they'd seen a response? It would make our lives for getting prior authorization so much easier. We could just send this over instead of a peer-to-peer and say, here is your data. But they did not because remember, this study was looking at all levels of severity in terms of severe ulcerative colitis. What do I mean by that? If you dig a little bit deeper into this data, there was indeed a trend towards better outcomes in patients that had predictably low albumin and high CRP. So if you look at these, the response, so yellow is higher dose. And you can see in patients that had an albumin of less than 2.5 grams, 64% had treatment response compared to 45% on the lower dose. And the same is true if you stratify this by CRP. If you had a CRP of more than 50, 60% response compared to 40%. So really what the PREDICT-UC study tells us is not everyone in the hospital with acute severe UC needs a higher dose. But certainly if you have a patient with low albumin and a high CRP, if you can, I would encourage giving them a higher dose of infliximab. This study was not powered to detect the difference by stratifying patients by albumin and CRP. But there's a clear trend here. And there's a lot of case reports and other open-labeled studies that have shown better outcomes in severe UC with hypoalbuminemia. Because what is hypoalbuminemia? Really a surrogate marker for higher drug clearance. So you're losing more infliximab, so you need more infliximab to keep up with the large pool of inflammatory cytokines. JAK inhibitors. This is a randomized controlled trial from India, my hometown, Ludhiana, where they looked at about 100 and some patients. These were patients that needed IV corticosteroids. They randomized them to receive TOFA 10 mg TID. Now that is one and a half times what we do in outpatient practice. The standard dose is BID. So 10 mg TID, in addition to IV steroids, looked at outcomes. No surprises here. As early as seven days, patients that received TOFA had better outcomes, better response, and at 90 days, lower rates of colectomy. There was one case of dural venous sinus thrombosis in the TOFA arm. What about OOPA? Well, in case of OOPA, data is limited. This is just a case series of about 25 patients from here within the US. Two-third of these received the 30 mg BID, higher than the standard dose of 45 mg, but very, very promising results. So certainly an option to consider, especially if you have a patient in the hospital that has failed a biologic, especially if that biologic happens to be an anti-TNF. So I want to spend just a minute here talking about surgery and why we as gastroenterologists should not think of it as failure of therapy. Because early surgery saves lives. I'll say it again. Early surgery saves lives in ulcerative colitis. These are data from the National Inpatient Sample. They looked at about 7,000 patients discharged after being admitted with acute severe ulcerative colitis. And what they found was patients that had surgery within the first six days of admission were less likely to die than patients that ended up having surgery past day six. And that trend persisted after adjusting for age, gender, comorbidities, insurance status, as well as the hospital volume. So across all these variables, early surgery patients were more likely to survive than surgery delayed past six days. So that brings me to an end. I'll summarize with a few key points, and then we'll open up the forum for questions. Early endoscopic assessment as soon as possible. Do start from pharmacologic DVT prophylaxis. Do not delay initiation of IV steroids. No benefit in exceeding 60 milligrams of IV solumedrol or equivalent. Treat infections simultaneously. Consult surgery early. And again, do not expect incremental benefit after the first 72 hours. You'll see the most bang that you're going to get for your buck with corticosteroids by 72 hours. And then choose rescue therapy based on prior exposure to TNF. And elective and early surgery saves lives. Thank you. Thank you. Dr. Carr, that was awesome. You know, one question came through, do you wait until the abscess is completely resolved to start Crohn's directed therapy? And my answer is no, not completely resolved. As long as the abscess is improving, let's say they got a drain in place, their leukocytosis has resolved and they've been on IV antibiotics for at least 24, 48 hours. There's no more fever. And I have clearance from ID or surgery that it's okay to resume or start therapy. And if I can get a biologic therapy started, I will get them started as soon as possible as long as I'm cleared from everyone. And clinically, they're getting better. The main reason is because the abscess has occurred because of a microperp or fistula and we need to treat the underlying Crohn's disease. Yes, go ahead. Excellent lecture. I would like to know your opinion about the use of intensified doses of infliximab in a hospitalized patient in both acute ulcerative colitis and severe Crohn's disease. Can you hear me? Is this mic working? Yes. Okay. So I didn't cover that aspect of PREDICT-UC. They actually compared three regimens. One was the standard, 5 mg per kg, 0, 2, and 6 weeks. The second was accelerated, 5 mg per kg at 0, 1, and 3 weeks. And the third was 10 mg per kg at baseline and then another one at week 1. What they found was no difference in colectomy outcomes. But I don't think the study was really powered adequately. So in my practice, rather than worrying too much about an accelerated regimen, I think a higher dose has greater benefit. So 10 mg per kg. If you're unable to get a second dose at week 1 but can get it at week 2, I wouldn't sweat it. You have to pick your battles. I think a better strategy would be to just do 10 mg per kg in the hospital, get them another dose in week 2. If you can, after the third dose, check drug levels to see if this is a salvageable situation or not. Regarding selumedrol for both Crohn's and ulcerative colitis, you said 60 mg IV once a day. You said 20 mg IV Q8 hours. I've always done once a day to minimize impact on sleep and psychiatric and anxiety and all that kind of stuff, even in ulcerative colitis. I'm wondering why the disparity between these two. DR. PARIKH It wasn't a disparity. So let me just clarify. Up to 60 mg to the day, so over 24 hours. So you can split it up accordingly. So I have done daily for some of those specific patients like you mentioned. They can't stand having the steroids at the evening time because they can't sleep. So I do this like 40 in the morning and that's it. But it's maximum 60 per day. That's what I meant. DR. ISAACSON Is there a therapeutic benefit to splitting the dose that is clinically important? DR. PARIKH I've seen it differently. And I'll answer just a bit. DR. PARIKH I don't think it's been demonstrated. This is just informed by experience. In my experience, I find greater benefit in splitting it Q8 than to give it as once a day. But I can't say that that's been demonstrated in studies. It's not an evidence-informed practice. It's more an experience-informed practice for me. DR. ISAACSON And I have patients who tell me, can you split it up? I feel like it wears off even for the few hours. So I do split it up for those patients too. Yeah. DR. ISAACSON Hi. Thanks for those great talks. Just in regard to acute severe UC, can you comment on how you handle the situation of not responding well to infliximab? And do you consider upaticidinib in that same patient? DR. PARIKH Yes. So that's an excellent point. You're talking about a second salvage therapy. You've given the patient a dose of infliximab and they're not getting better. What next? So I would encourage a second endoscopic look. Sometimes I've had the first FlexSig be negative for CMV, but the second one come back positive. And then there's no evidence for sequential rescue therapies. It has to be an informed decision with the patient because the risk of adverse outcomes goes up. And of course, that's also an important time to discuss the mortality risk for delayed colectomy. So I have that conversation with the patient. I think OOPA is a reasonable second choice. I wouldn't go from infliximab to cyclosporine. And the reason I think OOPA is a good second choice is because of its short half-life. If it's going to work, you'll know within 24 hours. So what I would do if you're considering a second rescue therapy, number one, reassess endoscopically. Make sure you get some objective evidence of things either not getting better or getting worse. And number two, inform discussion with the patient and identify with the patient finite time points that sure will give this other medicine a shot, but we'll know within 24 hours. And if things are not getting better, you really need to go to surgery. And I almost never, there's very few things where I say never for, but I would not have this discussion without having colorectal surgery on board because you need the patient to know that the likelihood of this working. It's really a coin toss. Yeah. Oh. Thanks for your talk. When you monitor the IBD, I can see that you see the CRP and albumin. What's your opinion about fecal co-protectant? So I don't use it so much in the inpatient setting because I prefer an early endoscopic assessment. Some patients, some folks and colleagues like to take a baseline level, but my problem with that is a calprotectin of 3,000 doesn't indicate inflammation that's three times as bad as a calprotectin of 1,000, right? It is not to be used in that qualitative sense. It tells us inflammation, yes, or inflammation, no. So I think you'll get much better quality data from an early endoscopic assessment or if you are doing bowel ultrasounds, bowel wall thickness, disruption of stratification. These are all objective markers that predict response to therapies, but I recognize that's not a modality that's utilized commonly. So I would encourage instead an early endoscopic assessment, and it does not need to be a colonoscopy. It does not need to be prepped, a flexi, unprepped or with a tap water enema. And the other thing with the fecal calpro to add to that is sometimes it can take some time for it to get the results back. CRP can almost order its stat essentially as well, but in some cases a patient's deteriorating, you don't even need to do that second look. You know the person's in trouble, they're heading toward surgery anyway, then I would move on to plan B or C at that time as well. You had a question? Okay, go ahead. Thank you for your talk. I have a question about perianal festilizing Crohn's disease. So currently in Australia we have a nationwide study looking at early dose escalation versus just standard dosing by closely monitoring the trough levels. What are your considerations in those patients who are initiating infliximab? So definitely we know in other festilizing, especially with infliximab studies that we need higher levels, right, to treat fistulas. It's not the baseline 3 or 12. You need to go up to 20, 25 in those cases. So I'm glad you're doing the study so we can actually see what those levels would be and have additional proof. But definitely I'm always dose escalating or frequency escalating the anti-TNFs. If I have a good level, let's say I have a level of 35 of infliximab and fistula is not doing anything, then I'm going to move on to a different mechanism. But if the level is 8 or 10 or even 12 or 15, I'm still going to try to push more of the drug because we have evidence that higher trough levels lead to better fistula healing, especially with the anti-TNFs. Okay. Do you have a question? Answered? Okay. Wonderful. Thank you all for listening and joining us. Thank you.

inflammatory bowel disease

Crohn's disease

ulcerative colitis

multidisciplinary care

steroids

nutritional support

anticoagulant prophylaxis

endoscopic assessment

biologics

individualized care