A Case Series of Kodamaea Ohmeri Infection: The Hidden Threat Unleashed

Intro: Kodamaea ohmeri, previously known as Pichia ohmeri, is an ascomycetous yeast that has emerged as an important cause of fungemia in immunocompromised patients. During the anamorphic stage this organism is also known as Candida guillermondii var. membranaefaciens. Method(s): We report five cases of Kodamaea ohmeri encountered from multicenter in Malaysia. Antifungal agent of choice will be discussed based on literature review. Finding(s): The cases were: (1) a contaminated peritoneal fluid in an adult patient on peritoneal dialysis;(2) a 60-year-old man with infected diabetic foot isolated K. ohmeri from a bone sample. Both cases discharged well without active antifungal fungal therapy. We observed fatality cases involving (3) an old man with underlying gastric adenocarcinoma who complicated with catheter- related bloodstream infection caused by K. ohmeri;(4) a patient with ventilator- associated pneumonia and septicaemic shock secondary to perforated terminal ileum;(5) and a severely ill COVID-19 stage 5b patient who passed away due to systemic fungaemia caused by K. ohmeri. Discussion(s): All three fatal cases received either amphotericin B or caspofungin as active antifungal agent. Literature evidence has shown that 40% of patient met demise despite on active antifungal agent, suggesting that currently no definitive antifungal agent proven to be a superior treatment option for K. ohmeri infection. Removal of indwelling medical device combined with antifungal therapy has favorable clinical outcome. Conclusion(s): Therefore, K. ohmeri infection in severely ill patients should be considered as a critical condition. Potential of alternative antifungal combinations need to be explored for an effective treatment option.Copyright © 2023

The 'Tic'king Bleeder: A Rare Case of Bleeding Dieulafoy's Lesion in a Jejunal Diverticulum

Introduction: Dieulafoy lesion (DL) is a relatively rare and arguably under-recognized condition, accounting for 1-2% of acute GI bleeding. Most bleeding DLs occur in the stomach, followed by the small intestine, with less than 1% occurring in the jejunum. Bleeding DL on a jejunal diverticulum is even more rare, with a handful cases described in the literature. Here we present a rare case of a bleeding DL in a jejunal diverticulum with its endoscopic management. Case Description/Methods: A 65-year-old female with history of COVID-19 infection one month prior to presentation treated with steroids and therapeutic anticoagulation presented to the ED after having multiple episodes of coffee-ground emesis and two episodes of syncope at home. Last dose of Apixaban was 12 hours prior to admission. Physical exam revealed BP of 90/60 on Norepinephrine infusion, HR of 96, abdominal exam was soft and nontender, DRE revealed melena. Hemoglobin/hematocrit was significantly decreased at 3.6/12.8. Patient was appropriately resuscitated with blood products and fluids, and she was scheduled for an EGD. Initial EGD did not identify a clear source of her bleeding, and she was scheduled for colonoscopy. Colonoscopy with deep cannulation of the terminal ileum up to 40cm revealed significant amounts of fresh blood all throughout the colon and terminal ileum. Decision was made for push enteroscopy, which revealed a jejunal diverticulum containing a Dieulafoy lesion with an overlying clot (Image A). The lesion was first injected with epinephrine at 2 sites followed by a clot removal overlying the lesion using 13-0 circular snare. A clear stigma of recent bleeding was noticed from the lesion after clot removal (Image B), after which 2 metallic clips were placed over the lesion to achieve hemostasis (Image C). The patient had no further episodes of bleeding and was follow up in clinic eventually, recovering well. Discussion(s): Because of the life-threatening nature of Dieulafoy lesions, identification is of paramount importance for treatment purposes. Jejunal DLs are a rare entity but should be considered in cases with negative bidirectional endoscopies. In our case, push enteroscopy helped identify the bleeding lesion. DL in a diverticulum can pose a challenge to the endoscopist due to difficulty of access to the lesion. Epinephrine injection followed by mechanical clipping showed a positive outcome in our case which can be considered while approaching bleeding DLs in a diverticulum. (Figure Presented).

A Rare Etiology for Ulcerative Colitis Flare

Introduction: Prior to colonoscopy, it is well understood that patients must undergo bowel cleansing. Based on the type of laxative, colonoscopy preparations fall into two categories - polymer-based formulas (PEG) and saline-based formulas (NaP). Both types of bowel preparations are deemed to be relatively safe and part of routine practice. However, we describe the rare case of an ulcerative colitis (UC) flare due to the bowel preparation formula. Case Description/Methods: A 29-year-old female with diagnosis of UC, presently in clinical and biochemical remission on oral mesalamine, contracted COVID-19 and had reactivation of UC symptoms. After being on budesonide tablets and rectal foam for two months, patient achieved clinical remission, and a surveillance colonoscopy was performed which revealed normal colon and terminal ileum except mild congestion in the cecum (Figure A). Pathology revealed unremarkable mucosa in the entire colon except for chronic active colitis in the cecum. Immediately following this colonoscopy, the patient started to experience another severe UC flare requiring hospitalization. The patient's laboratory work-up was normal except for an elevated fecal calprotectin (1710). Stool infectious work-up was negative and the patient denied any NSAID or antibiotic use. The patient underwent a repeat colonoscopy which revealed severe Mayo 3 pancolitis (Figure B) in comparison to a stable colonoscopy a few weeks prior. It was revealed that for her initial colonoscopy, she had used SUPREP bowel prep kit. On prior colonoscopies she had used MiraLAX bowel prep with no adverse effects. During hospitalization, the patient was started on biologic therapy with good effect. Discussion(s): There are no clear guidelines on appropriate bowel preparation formula for the inflammatory bowel disease (IBD) population. Sufficient literature exists to confirm that NaP can irritate the intestinal mucosal wall. Moreover, numerous animal experiments have employed dextran sodium sulfate for chemical induction of intestinal inflammation to mimic UC flares in humans [1]. Thus, it can be surmised that because SUPREP ingredients contain sodium sulfate, the potential for UC flare is higher. It is pertinent for practitioners to be aware of the possible rare adverse effects of saline-based formulas, especially when treating the IBD population.

Mesenteric Ischemia: A Case of Extrapulmonary Presentation in COVID-19

Coronavirus 2019 (COVID-19) is a predominantly respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It creates a hypercoagulable milieu, manifesting at varied extrapulmonary sites as pulmonary embolism, deep venous thrombosis, stroke, myocardial infarction, and mesenteric ischemia. The pathophysiology behind this hypercoagulability is still not entirely understood, although a heightened systemic inflammatory response to the virus is deemed responsible. We herein report a case of a 36-year-old healthy male who presented with an acute abdomen and was found to have extensive mesenteric and portal venous thrombosis with bowel gangrene. The patient underwent emergency exploration with ileal resection and end-ileostomy. The hypercoagulability panel was negative, but a postoperative chest radiograph revealed suspicious ground-glass opacities. Given the ongoing global COVID-19 pandemic, we considered testing for SARSCoV-2. A positive test for SARS-CoV-2 led us to attribute the thrombotic event to COVID-19. With anticoagulation and supportive therapy, the patient went on to make a steady recovery. A non-specific clinical manifestation of COVID-19 necessitates considering mesenteric venous thrombosis as a differential diagnosis in patients with acute abdomen.Copyright © 2023 Author.

Recurrent intussusception with ileal perforation as a complication of Blue Rubber Bleb Nevus Syndrome in a pediatric patient

Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital condition, characterized by multiple venous malformations that may involve any organ system, most commonly the skin or the gastrointestinal tract. These lesions are often responsible for chronic blood loss and secondary anemia, and in rare situations may cause severe complications such as intussusception, volvulus, and intestinal infarction. Intussusception as a complication of BRBNS, although a known complication of the disease, has rarely been reported, especially in the Philippines. In the Philippine Society for Orphan Disorders, only 2 cases of BRBNS are currently included in the organization, including the patient presented in the case report. The treatment of BRBNS that involves the gastrointestinal tract depends on the extent of intestinal involvement and severity of the disease. The treatment aims to preserve the GI tract as much as possible due to the high recurrence in the disease. In this case report, we present a 13 year-old male with BRBNS with previous history of intussusception, successfully managed conservatively;however, upon recurrence, underwent exploratory laparotomy wherein a subcentimeter perforation in the antimesenteric border of the proximal ileum was noted, together with a gangrenous intussuscipiens, and multiple mulberry-like formations on the antimesenteric border of the small bowels. Histopathological findings of the resected bowels showed multiple cavernous hemangiomas consistent with BRBNS. The postoperative course of the patient was unremarkable.Copyright © 2023 The Authors

Using urgent small bowel ultrasound (SBUS) as a tool for decision-making in patients with inflammatory bowel disease (IBD): Retrospective analysis of United Kingdom (UK) patients' outcome

Background: In the UK, magnetic resonance enterography (MRE) and colonoscopy are the gold standard assessment for mucosal disease activity in IBD. Both techniques require bowel preparation, may be poorly tolerated and are often subject to delay due to capacity issues. In several European centres, ultrasound is used as an alternative tool for disease activity monitoring and clinical decision-making. Recent studies confirm excellent sensitivity, specificity, correlation with MRE / colonoscopy and robust inter-observer agreement. In the UK, a lack of US training in IBD physicians has hindered development of accessible SBUS. In view of issues with MRI capacity during the covid pandemic, a dedicated small bowel ultrasound list with a gastroenterology fellow and a specialist radiology consultant for urgent IBD patients was initiated. Method(s): Records of IBD patients undergoing SBUS between June 2022 and November 2022 were reviewed. SBUS assessed disease activity (vascularity, bowel wall thickness, mesenteric fat and lymphnodes), length of disease, presence of obstruction or fistulating disease. Patients were then retrospectively asked to rate their SBUS experience compared to previous MREs. Result(s): 53 SBUS's (46 (86.7%) CD;2 (3.7%) UC) were performed on a dedicated SBUS list by a gastroenterology fellow and specialist radiology consultant during the study. In 29 patients (54.7%), the area of interest was the terminal ileum. SBUS detected disease complications in 7 (2 (3.7%) patients with obstructive disease, and 5 (9.4%)) patients with penetrating disease. The average waiting time from the point of referral to SBUS was 4.7 weeks, compared to an average waiting time for MRE of 20 weeks. Treatment response was assessed in 18 patients (33.9%). We were able to make treatment decisions with 32 patients (60.3%) based on their SBUS results without further assessment. In 10 patients (18.8%), SBUS was used to confirm a diagnosis in addition to colonoscopy. 18/22 ( 81%) patients reported a preference for SBUS compared to MRE (preference score of 4.5 on scale of 1-5). Conclusion(s): We developed an urgent SBUS service to aid timely clinical decision-making for IBD patients. In our practice, SBUS is an accurate tool to assess disease activity, significantly reduces patients waiting times and is the patient's preferred investigation. There is a clear unmet need to train IBD doctors and radiologists in SBUS.

Ask twice: The importance of repeated faecal calprotectin testing prior diagnostic colonoscopy in an adult inception cohort

Background: Elevated Faecal Calprotectin (FCP) is established as a valuable tool in differentiating Inflammatory Bowel Disease (IBD) from Irritable bowel syndrome (IBS) and monitoring IBD activity. Initial implementation studies in the UK demonstrated benefit from repeat testing to exclude false positives. This is not currently mandated by IBD consensus guidelines. Growing waiting times are increasing pressure to include a single result in straight to test pathways. No one level for significant elevation is defined with levels between 100-250ug/g used We present our experience of the real-world utility of FCP used in a primary care referral pathway Methods: From Jan 2021-Nov 2022, new referrals were streamed into a rapid access 'Inception IBD' clinic on the basis of symptoms and raised FCP. A repeat FCP (kit sent in advance) was brought to the first appointment, with same day processing using the Buhlmann fCAL Turbo Test. Results and accompanying diagnosis and outcome data was collected prospectively. There was no standardised testing interval but median time from referral to review was 34 days Results: A single FCP was available for 425 patients with a final diagnosis Two pre-treatment FCPs were available in 185. Median initial FCP was 949ug/g in those subsequently diagnosed with IBD (Ulcerative colitis 1162ug/g, Crohn's 893ug/g) vs 353ug/g in those without IBD This difference heightened on retesting, with median FCP in IBD 749ug/g vs 34ug/g in non-IBD (Fig 1). FCP fell between 1st and 2nd measurement in 88.6% of patients who had IBD excluded In IBD, baseline FCP showed strong correlation with established disease activity markers (Fig 2) Baseline FCP levels were significantly higher in IBD patients who went on to require biologic treatment (Mann-Whitney U 2763, p<0.001) A variety of FCP cut-off values were assessed (Fig 4). A two sample >200ug/g cut off performed best as assessed by Area Under the Curve (AUC). However, sensitivity fell to 81.5% at this level Of 15 IBD patients who didn't have two FCPs >200ug/g, 7 had an increase between the 1st and 2nd FCP (median 147 vs 487ug/g). The remaining 8 comprised 4 ileal Crohn's, 3 mild proctitis and 1 stricturing colonic Crohn's in whom FCP failed to correlate with disease activity Overall, 83% (48/58) of patients with increasing 1st to 2nd FCP were diagnosed with IBD Conclusion(s): Our data supports repeat testing of FCP to avoid unnecessary investigations adding to post COVID endoscopy backlogs. A cut off of two values >200ug/g had the best overall performance but can miss a small number of IBD cases, particularly those with isolated ileal disease or a more indolent disease course. This cut off should not be used in those with a marked increase between 1st and 2nd result, where IBD is likely.

Acute Mesenteric Thrombosis, Small Intestine Necrosis and Peritonitis as a Complication of Covid-19 - a Case Report

Introduction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to a family of ribonucleic acid (RNA) viruses, causing novel coronavirus disease 2019 (COVID-19). Because of a global inflammatory response and endothelial damage, COVID-19 may predispose to coagulation disorders and severe thrombotic events. Case presentation. A 62-year-old man patient was admitted for COVID-19 pneumonia and abdominal pain for 10 days. Because of the rapid deterioration of the clinical status, shock and evidence of peritoneal irritation, the patient was consulted by a surgeon. The native spiral computed tomography (CT) of the abdomen detected enlarged colon filled with air collections and hydro-aeric levels. The surgical intervention revealed diffuse peritonitis with necrosis of the distal ileum secondary to mesenteric thrombosis. A partial resection of the ileum was done. The histological examination showed an infarcted small bowel, with hemorrhage, vascular thrombosis, and signs of necrotizing endovasculitis. Conclusions. SARS-CoV-2 binds to ACE2 receptor, which results in increased signalling by thrombin receptors on platelet and endothelial cells, leading to coagulopathy. In older patients presenting with abdominal pain, shock and peritonitis, the most common underlying cause is mesenteric thrombosis which could be a complication of COVID-19.Copyright © 2022 Balkan Medical Union.

Maternal fructose boosts the effects of a Western-type diet increasing SARS-COV-2 cell entry factors in male offspring.

Fructose-rich beverages and foods consumption correlates with the epidemic rise in cardiovascular disease, diabetes and obesity. Severity of COVID-19 has been related to these metabolic diseases. Fructose-rich foods could place people at an increased risk for severe COVID-19. We investigated whether maternal fructose intake in offspring affects hepatic and ileal gene expression of proteins that permit SARS-CoV2 entry to the cell. Carbohydrates were supplied to pregnant rats in drinking water. Adult and young male descendants subjected to water, liquid fructose alone or as a part of a Western diet, were studied. Maternal fructose reduced hepatic SARS-CoV2 entry factors expression in older offspring. On the contrary, maternal fructose boosted the Western diet-induced increase in viral entry factors expression in ileum of young descendants. Maternal fructose intake produced a fetal programming that increases hepatic viral protection and, in contrast, exacerbates fructose plus cholesterol-induced diminution in SARS-CoV2 protection in small intestine of progeny.

DISSEMINATED HISTOPLASMOSIS IN THE SETTING OF IMMUNOSUPPRESSION DUE TO CROHN DISEASE

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus most commonly encountered as an opportunistic infection in immunosuppressed patients, particularly those with HIV/AIDS. However, patients immunosuppressed from other causes can also be at risk. Here is presented the case of a patient on multi-immunosuppressant therapy as treatment for Crohn's disease, who developed disseminated histoplasmosis. CASE PRESENTATION: A 44-year-old male with a past medical history of Crohn's disease (previously been on azathioprine, adalimumab and currently on Prednisone therapy), recently started on infliximab infusion for uncontrolled symptoms of IBD, diabetes mellitus, hypothyroidism, and COVID-19 infection (not requiring oxygen therapy) one month prior to the current admission initially presented to the hospital with chief complaints of exacerbated weakness, myalgias, fevers and diarrhea for 5 days;Symptoms of weakness, myalgias began after first infusion of infliximab and it got progressively worse after the 2nd infusion 2 weeks prior to the admission. White Blood Cell count was 1.1 K/uL, platelet count was 7 K/uL, hemoglobin was 7.9 g/dL. CRP was elevated to 142 mg/L, and ferritin was elevated to 39,000 ug/L. CT abdomen and pelvis demonstrated probable rectosigmoid colitis and splenomegaly. Subsequent chest x-ray demonstrated bilateral opacities with haziness over bilateral lung fields. Respiratory viral panel, stool panel, blastomyces antigen, cryptococcal antigen, toxoplasma antibodies, HIV antibody, CMV PCR, and blood cultures were unrevealing. Urinary histoplasma antigen was positive, and BD-glucan was elevated to over 500 ng/L. EBV panel was positive for reactivation, with EBV DNA 2.02 IU/mL. He was subsequently started on amphotericin B lipid complex, with itraconazole destination therapy. He was treated empirically for pneumocystis jiroveci pneumonia (PJP) with sulfamethoxazole-trimethoprim due to him being on chronic Prednisone therapy. Echocardiogram demonstrated left ventricular ejection fraction (LVEF) of 40%, with diffuse hypokinesis and wall motion abnormalities, posing some question of myocarditis. He was later discharged home in an improved state. DISCUSSION: Disseminated histoplasmosis in the setting of Crohn's disease on chronic immunosuppressive therapy has been very rarely reported,(1) with similar reports in patients on immunosuppressive therapy in the setting of rheumatologic disease being slightly more common.(2) The most commonly involved areas in gastrointestinal histoplasmosis are the terminal ileum and colon,(3) with this patient's rectosigmoid colitis and symptomatology being consistent with this pattern. The patient's myocarditis is also consistent with disseminated histoplasmosis infection. CONCLUSIONS: Clinicians should maintain suspicion for opportunistic infections in patients on immunosuppressive therapy in the setting of critical illness. Reference #1: Bhut, B., Kulkarni, A., Rai, V. et al. A rare case of disseminated histoplasmosis in a patient with Crohn's disease on immunosuppressive treatment. Indian J Gastroenterol 37, 472–474 (2018). https://doi.org/10.1007/s12664-018-0886-1 Reference #2: Wood KL, Hage CA, Knox KS, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167(9):1279-1282. doi:10.1164/rccm.200206-563OC Reference #3: Galandiuk S, Davis BR. Infliximab-induced disseminated histoplasmosis in a patient with Crohn's disease. Nat Clin Pract Gastroenterol Hepatol. 2008;5(5):283-287. doi:10.1038/ncpgasthep1119 DISCLOSURES: no disclosure on file for Donald Dumford;No relevant relationships by Abhilash Bhat Marakini No relevant relationships by Palak Rath No relevant relationships by Sterling Shriber

A CASE OF EGGERTHELLA BACTEREMIA IN A PATIENT WITH COVID-19

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: We present a case of Eggerthella bacteremia in a patient with COVID-19. CASE PRESENTATION: A 69-year-old woman presented to the emergency room with chief complaint of cough, dyspnea, and malaise. After testing positive with a home COVID-19 test three days earlier, she continued to have worsening respiratory status and was brought in via ambulance. She was found to be tachycardic and hypoxic, requiring high-flow oxygen to maintain saturation in the emergency department. Chest X-ray showed bilateral patchy opacities consistent with multifocal COVID-19 pneumonia, and she was admitted to the intensive care unit for acute hypoxic respiratory failure. COVID-19 drug therapy was initiated, including baricitinib, remdesivir and decadron. Shortly after hospitalization, she began to endorse worsening abdominal pain. Physical exam elicited tenderness to palpation of her right lower quadrant. Abdominal CT scan showed distal ileum fluid collection concerning for possible bowel perforation. She underwent exploratory laparotomy which confirmed perforation, and a small bowel resection with anastomosis was performed. Blood cultures were positive for gram-positive bacilli, which were further identified as Eggerthella species. She required mechanical ventilation for worsening respiratory function post-surgery but remained unresponsive on the ventilator. The patient was administered vancomycin but continued to decline and eventually expired. DISCUSSION: Eggerthella is an anaerobic, gram-positive bacilli present in the gut microflora. Eggerthella infection has most often been reported in intra-abdominal infections. However, cases of bacteremia infection remain sparse. Most infections have been associated with other gastrointestinal processes including Crohn's disease, ulcerative colitis, appendicitis, and diverticulitis abscesses. Our case involved a patient with no significant gastrointestinal history admitted for COVID-19 pneumonia infection on baricitinib complicated by bowel perforation and bacteremia. Bowel perforation is a known risk factor of baricitinib use, and these risks should be discussed with the patient before beginning therapy. Overall mortality for Eggerthella species infection remains high, with some estimates as high as 31%. Much remains unknown about the impact on gut microbiome by SARS-CoV-2, however, early research suggests a higher rate of fungal co-infection in patients with COVID-19. As the literature on COVID-19 expands, more and more unusual pathogens such as Eggerthella may be found to contribute to the morbidity and mortality of patients being treated for COVID-19. CONCLUSIONS: Unusual pathogens such as Eggerthella may complicate a patient's hospital course while undergoing treatment for COVID-19. Reference #1: Alejandra Ugarte-Torres, Mark R Gillrie, Thomas P Griener, Deirdre L Church, Eggerthella lenta Bloodstream Infections Are Associated With Increased Mortality Following Empiric Piperacillin-Tazobactam (TZP) Monotherapy: A Population-based Cohort Study, Clinical Infectious Diseases, Volume 67, Issue 2, 15 July 2018. Reference #2: Gardiner BJ, Tai AY, Kotsanas D, et al. Clinical and microbiological characteristics of Eggerthella lenta bacteremia. J Clin Microbiol. 2015. Reference #3: Lau SK, Woo PC, Fung AM, Chan K-M, Woo GK, Yuen K-Y. Anaerobic, non-sporulating, gram-positive bacilli bacteraemia characterized by 16s rrna gene sequencing. Journal of medical microbiology. 2004. DISCLOSURES: No relevant relationships by Kristin Davis No relevant relationships by Charles Peng

Identification of Persistent Sars-Ncov-2 Viral Presence in the Intestines of Multiple Pediatric Patients Suggests Possible Common Etiology of Gi Long Covid

Background: The phenomenon known as "Long Covid," (LC) marked by post-infectious symptoms of a wide variety, and typically not associated with initial infectious severity, has the potential to become a tremendous public health burden as infections continue at a high rate. Variations of LC may impact over 80% of patients, with unclear pathogenesis, although many speculate that persistent viral presence in end-organ tissue may drive local changes. We previously published a case report noting persistent SARS-nCoV-2 activity in the cecum of a patient 3 months after initial infection (Arostegui et al, JPGN Reports, 2022). We have sought to expand that finding by assessing additional patients who have undergone endoscopic evaluation for presence of SARS-nCoV-2 nucleocapsid, seeking to expand our understanding of the clinical effects of persistent infection. Method(s): We identified 6 patients with onset of symptoms in the post-SARS-nCoV-2 window, who had undergone EGD/colonoscopy without histopathological diagnosis. New blank slides were cut and sent for staining at Histowiz inc (Brooklyn, NY), with rabbit monoclonal SARS-CoV-2 nucleocapsid antibody (GTX635686, 1:10,000). Resulting slides underwent blinded pathology review to identify positives. Chart review was completed on patients who were identified as positive, including histopathology data from endoscopy, medical history, presentation, laboratory results and clinical course. Result(s): Including our initial report, we have identified 4 female patients ages 11-16 to date. Viral presence was identified in the duodenum and TI, but only in one patient in the colon (cecum). Patients presented for evaluation of a variety of GI manifestations including chronic abdominal pain (100%), nausea and vomiting (50%), loss of appetite (50%), tenesmus (50%), hematochezia (25%) as well as weight loss (50%). Notably, of the 4 patients identified, only 1 had a known history of confirmed SARS-nCoV-2 infection. Endoscopic findings in the intestine were normal with the exception of edema noted in the cecum of two patients. Mucosal biopsies were also positive for notable (if typically felt to be non-pathologic) lymphoid aggregates in the Colon (75%) as well as in the Terminal Ileum (50%). Clinical information is summarized in Table 1. Conclusion(s): Additional identification of persistent SARS-nCoV-2 presence in patients ranging from 3-18 months after symptom onset demonstrates a high likelihood that persistent viral presence contributes to post-infectious symptoms in many patients. Patients demonstrated "red flag" symptoms like nighttime awakening with pain, weight loss, and elevated inflammatory markers or calprotectin, but symptomatically improved over time and with measures targeted at IBS. Our limited sample size prevents determination of typical location of persistent viral activity, but it is notable that symptoms for colonic vs. SI persistence were clinically consistent, with diarrhea in colonic persistence and early satiety/pain characterizing SI persistence. Most notably, we have identified a tendency for persistent infection to occur, potentially explaining at least a subset of persistent IBS-like symptoms associated with GI LC. Further work is necessary to determine exactly the prevalence of this issue, as well as to characterize the natural history of the clinical course, and possible effective therapies. (Table Presented).

Functional Gastrointestinal Disorders as a Post-Covid Infection Sequel in Pediatric Patients in Mexico

INTRODUCTION: The rate of pediatric patients diagnosed with Sars Cov 2 has increased since the early stages of the pandemic. Gastrointestinal symptoms have been demonstrated to be relatively common in pediatric COVID-19 patients as well as severe complications like PIMS syndrome because of the expression of ACE II in different areas of the digestive tract which serves as a receptor for their entry and infection in the body. During the last months of the omicron variant wave, we observed some gastrointestinal conditions in pediatric patients days after the resolution of the Sars Cov 2 acute infection period, sparking our interest to execute further research and analysis. OBJECTIVE(S): Describe the presence of functional gastrointestinal disorders as a post-covid infection sequel METHODS: We performed a descriptive, cross-sectional, observational, retrospective study, were we recollected the clinical and epidemiological data from the medical records of pediatric patients with a history of Sars cov-2 infection confirmed with positive PCR or antigen (sars cov-2) tests at Hospital Angeles Lomas, Mexico City. We included children from 6 months up to 16 years of age, who presented functional gastrointestinal disorders at a minimum 15 days after the infection that fulfilled Rome IV criteria. We evaluated the frequency and proportion of the qualitative variables;we obtained the arithmetic mean and the standard deviation for the quantitative variables with normal distribution RESULTS: We included data from 30 patients with confirmed covid 19 diseases by positive pcr or antigen (sars cov-2) tests, with a mean age 5.327 +/- 3.8 years Min: 7 months Max: 16 years, with a female predominance of 56.7% vs 43% male patients. During the acute infection by covid, 20% presented respiratory symptoms, 13.3% gastrointestinal symptoms, 36.7% only fever, 3.3% dysgeusia and 26.7% were asymptomatic. Adequate nutritional status was detected in 93% of the patients. The mean days the patients presented manifestations was 32 +/- 14 days, at a minimum 15 days, with a maximum of 63 days, being the most frequent functional gastrointestinal disorders: abdominal pain 90%, bloating 76%, vomit and reflux 33%, diarrhea 30%, constipation 26.7%. There was no weight loss in the patients, the appropriate treatment was given for each case. There was no complication in 90% of the patients, 10% presented acute abdominal pain and were transferred to the emergency room, 1 patient was diagnosed with appendicitis and 2 patients with mesenteric lymphadenitis. CONCLUSION Special attention must be paid to toddler and preschooler patients with Sars Cov 2 infection, regardless of the clinical manifestation in acute infections, mild or asymptomatic, functional gastrointestinal disorders may occur in the first 2 months after a positive PCR test. The ileum and the colon are places in which there is a greater expression of the ACE II, so when the enterocytes are invaded by SARS CoV-2, they may produce alterations in absorption and other mechanisms that could be the cause of these consequences. It is of vital importance that all pediatricians are aware of the consequences of the disease to prevent misdiagnosis.

Angiotensin converting enzyme 2 in the gastrointestinal tract: binding with coronavirus and its consequences

Introduction: Angiotensin converting enzyme 2 (ACE2) is expressed in several cell types in the body including the gastrointestinal (GI) epithelium. Objective:To provide an overview of the normal distribution of ACE2 in the GI tract, altered ACE2 expression notably in coronavirus infection and its consequences. Materials and Methods: Pubmed and google scholar were searched using the key words ACE2 paired with GI tract, intestinal permeabilty, gut microbiota, inflammatory bowel disease. Results and Discussion: ACE2 is highly expressed in the ileum and colon in human being as well as in rodents. In this current situation of COVID-19 pandemic, downregulation of ACE2 has been reported due to internalization of the ACE2-virus complex within the cells. Although researches are still in infancy in this topic, altered luminal microbiota, increased intestinal permeability, higher level of inflammatory markers and deficient nutrient transport has been reported due to altered ACE2 expression. Conclusion:Altered expression of ACE2 has the possibility to hamper normal physiological function of the GI tract and might affect GI disease progression and prognosis.

LEFLUNOMIDE-INDUCED COLITIS IN IMMUNOSUPPRESSED PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS

Background: Leflunomide is an oral disease-modifying antirheumatic drug (DMARD), with anti-inflammatory and immunomodulatory properties that has been in use since 1998. Common leflunomide side-effects include gastrointestinal symptoms (nausea, abdominal pain and diarrhea), occurring in 10-20% of patients treated with leflunomide. Scarce evidence exists that leflunomide can cause colitis. Aims: We present the case of a 61-year-old female, with Lupus Erythematosus who presented with colitis induced by long-term leflunomide treatment. Methods: Case report and review of literature Results: A 61-year-old female was seen by the gastroenterology team with complaints of diarrhea ongoing for 6 weeks associated with 10 lb weight loss. The patient had a complex medical history, including lupus, hypothyroidism, asthma, atrial fibrillation, recurrent C. difficile infection, Bell's palsy and avascular necrosis secondary to long-term corticosteroid therapy. Previous immunosuppressive therapies included prednisone, mycophenolic acid (Myfortic), hydroxychloroquine, azathioprine, mycophenolate (CellCept) but due to multiple intolerances, she was initiated on leflunomide in 2014 and has been maintained on it since. Stool analysis ruled out infectious causes. COVID-19 testing was also negative. A CT of the abdomen revealed pancolitis. This was confirmed on colonoscopy, which revealed mild, Mayo 1 pancolitis and normal terminal ileum. She was initiated on Mezavant as a treatment for possible ulcerative colitis. However, during the hospitalization her symptoms, worsened and bloody diarrhea was noted. She underwent a subsequent endoscopic evaluation which revealed more severe disease, Mayo 2-3 colitis, with mucosal hyperemia and ulcerations, as well as effacement of the vasculature. Initial pathology results revealed mild colitis, but repeat pathology results revealed moderate active colitis, with cryptitis, crypt abscesses and significant apoptosis consistent with drug-induced colitis. Given these findings, the diagnosis of leflunomide-induced colitis was made. Leflunomide was therefore discontinued, the patient was initiated on a higher dose of corticosteroids and cholestyramine was initiated. Following these measures, her diarrhea resolved. Conclusions: Leflunomide may cause diarrhea in up to 33% of patients. Challenges related to the diagnosis of leflunomide-induced colitis exist, including the rarity of the diagnosis, a not completely understood mechanism for acute leflunomide-induced diarrhea, as well as variable endoscopic and histologic findings associated with the diagnosis. This report illustrates a case of leflunomide-induced colitis which should be considered in patients on leflunomide, who present with symptoms of abdominal pain and diarrhea, even years after medication initiation.

2021 CDDW Abstracts

The proceedings contain 243 papers. The topics discussed include: KRT15+ tumor cells as putative cancer stem cells in esophageal cancer;the circadian timing of inflammatory bowel disease;GM-CSF autoantibodies: predictors of Crohn's disease development and a novel therapeutic approach;an INULIN-type Fructan enriched exclusive enteral nutrition formula modulates the gut microbiome and promotes expansion of anti-inflammatory T cell subsets to suppress colitis;dietary tryptophan modulates kynurenine and indole production in healthy individuals;dorsal root ganglia neuronal responses and substance p production are higher in male mice;food antigen-stress interaction leads to increase pain signaling in ileum and colon via STAT6 in an IBS model;risk perception and knowledge of COVID-19 in patients with celiac disease;pre-treatment HLADQA1-hladrb1 testing for the prevention of azathioprine-induced pancreatitis in inflammatory bowel disease: a prospective cohort study;and a high salt diet synergizes with UC microbiota to induce a proinflammatory immune tone in immunocompetent gnotobiotic mice.

Screening and identification of host proteins interacting with PDCoV S1-CTD

The C-terminal domain (CTD) of porcine deltacoronavirus S1 subunit is the main region which induces the neutralizing antibody. S1-CTD was expressed by HEK-293T eukaryotic expression system and purified, and porcine ileal epithelium cells membrane proteins were extracted to investigate porcine host proteins that interact with it. Thirty-two suspected interacting host proteins were obtained by co-inmunprecipitation (Co-IP) and mass spectrometry. Eukaryotic expression plasmid of KIF1 binding protein (KIFBP) was constructed, and the interaction between KIFBP and S1-CTD was identified by Co-IP and laser confocal microscopy. All results proved that KIFBP interacted with S1-CTD and co-located in cytoplasm. Further research indicated that overexpression of KIFBP could effectively reduce the viral mRNA level and the viral titer in which the mRNA level decreased by about 70%, and the viral titer decreased by 101.6TCID50. In conclusion, a host protein KIFBP interacting with PDCoV S1-CTD was screened and identified in this study which provides a theoretical basis for understanding the pathogenesis of PDCoV.

MIS-CM imicking Acute Appendicitis

Introduction: Abdominal pain is one of the most common complaints seen in the pediatric acute care setting. SARS-CoV-2 disease in children includes a hyperinflammatory syndrome called Multisystem Inflammatory Syndrome in Children (MIS-C). Gastrointestinal symptoms are most common in pediatric acute SARS-CoV-2 infection as well as in MIS-C. Case Description: A 13- year-old female presented with diffuse lower abdominal pain for 3-days. Pain was 10/10 in intensity, worsened with movement, and had associated constipation, anorexia, nausea, and vomiting. Exam showed an ill-appearing female with labile vitals and generalized lower abdominal tenderness with good bowel sounds. Ultrasound suggested features of acute appendicitis but a follow-up CT did not visualize the appendix. She was admitted to the inpatient unit after routine screening revealed positive SARS-CoV-2 antibody but negative PCR. She received IV fluid bolus, narcotic analgesics, and ampicillin-sulbactam preoperatively. Within hours, she spiked high-grade fevers (101.4F), sustained hypotension, and tachycardia with concern for sepsis secondary to a possible ruptured appendix. She underwent emergency diagnostic laparoscopy which revealed bile-tinged fluid in the lower quadrant, a mildly inflamed appendicular tip without perforation, and thickened mesenteric nodes within the inflamed distal ileum. Intra-operatively, she had persistent hypotension requiring fluid boluses and vasopressors. Her admission labs revealed elevated inflammatory markers, deranged coagulation profile, and elevated cardiac enzymes. Her differential diagnosis was then revised to include MIS-C and severe sepsis. Antibiotic coverage was broadened to Vancomycin and Meropenem. An Echocardiogram showed mitral regurgitation with moderately to severely decreased right and left ventricular systolic dysfunction with an ejection fraction of 32.8% The patient was then transferred to the pediatric cardiac critical unit where she received treatment with IVIG, steroids, and anticoagulants. Her clinical status and lab studies improved with EF > 50%. She was discharged from the intensive care unit after 7 days and has had an uneventful follow-up. Discussion: Differential diagnosis for acute lower abdominal pain in an adolescent female is broad. Similar cases with predominant GI symptoms and later generalized multisystem involvement have been reported, however, most were managed conservatively. Two reports have been published on MIS-C presenting as acute appendicitis, but neither had significant cardiac involvement. Our patient's presentation can easily be confused with an acute surgical abdomen but the pathology report confirmed a congested appendix without any fecoliths supporting either inflammation or vasculitis as the cause for her presentation, which is in concordance with the hyperinflammatory state that has previously been described in patients presenting with a history of past SARS-CoV- 2 infections. Conclusion: MIS-C can mimic serious pediatric illnesses including sepsis, acute abdomen, and Kawasaki disease. Clinicians should have a low threshold for suspecting MIS-C, as prompt treatment can be lifesaving. Universal screening for COVID-19 infection with PCR and antibody tests can expedite the diagnostic evaluation of severely ill children. Showing reactive wall thickening of the cecum and small bowel loops (red arrow) and enlarged mesenteric lymph nodes (yellow arrow). The appendix could not be visualized here.

REGULATION OF INTESTINAL ACE2 EXPRESSION BY THE BILE ACID RECEPTOR GPBAR1 IS MEDIATED BY A GPBAR1/GLP-1/GLP-1R AXIS

Background: ACE2 is a carboxypeptidase homolog to the dipeptidase ACE but with different substrate specificity;while ACE principally acts as a carboxydipeptidase (peptidyldipeptidase) removing the C-terminal dipeptide from Ang I to form Ang II, ACE2 functions exclusively as a carboxypeptidase removing a single C-terminal amino acid from Ang II generating Ang- (1-7) or, much less efficiently, from Ang I forming Ang-(1-9). ACE and ACE2 than playing a key role in regulating the renin–angiotensin–aldosterone system (RAAS). In the normal lung, ACE2 mRNA is mainly expressed by type II alveolar epithelial cells and endothelial cells, but the level of expression increases in response to inflammation while is downregulated in response to SARS-CoV infection. ACE2, mRNA and protein, is highly expressed in the gastrointestinal tract, with the higher expression detected in epithelial cells of the ileum and the colon where mediates the absorption of amino acids. ACE2 expression in the intestine undergoes regulation in response to a variety of factors including intestinal microbiota and inflammation. Furthermore, previous studies have suggested that insulinotropic factor glucagon like peptide (GLP)-1 might regulate ACE2 expression in the heart, suggesting a potential interaction of GLP1 with ACE2. GPBAR1, G Protein Bile Acid Receptor, is robustly expressed in the gastrointestinal tract and its activation in the intestine promotes the release of GLP-1. Aim: to investigate the possible interaction between bile acids via GPBAR1 and the expression of ACE2 in the gastrointestinal tract. Materials and Methods: HT29 cells treated with TNF-α + IL-1β and mouse models of colitis were used to assess ACE2 expression and treatment with BAR501, a GPBAR1 agonist, was used to investigate its modulation. Results: The inflammatory stimulus increased the expression of Ace2 in HT29 cells and in colon of mice according to the data obtained in human samples from patient with IBD. GPBAR1 agonism by BAR501 relieved inflammation both in vitro and in vivo but in vitro this effect induced down-regulation of ACE2 while in vivo administration of BAR501 increased ACE2 expression. In mouse model of colitis, inflammation up-regulated also the GLP-1 gene expression that was further increased by BAR501 and instead, the administration of Exendina- 3, a GLP-1R antagonist was able to block the up-regulation of Ace2 expression exerted by BAR501. Conclusions: In conclusion, our results demonstrate that both in vivo and in vitro activation of GPBAR1 by a selective agonist exerts an anti-inflammatory effect. On the other hand, in vivo activation of GPBAR1 in the colon induces the release of GLP-1, which mediates some of the anti-inflammatory effects exerted by the receptor, and induces further upregulation of Ace2 by GPBAR1/GLP-1/GLP-1R axis.(Figure Presented)

PERSISTENT IMMUNE CELL ABNORMALITIES IN THE INTESTINAL MUCOSA OF PATIENTS AFTER RECOVERY FROM COVID-19 INFECTION

Background: Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (GI) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, in-vitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SARS-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19. Methods: Individuals with previous COVID-19 diagnosis (by either RT–PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells) and NK cells. Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody. Results: Thirty subjects with a previous history of COVID-19 (post-COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC)1 (lin-HLA-DRhiCD14- CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14-CD11c+CD1c+) were noted in the colon. Among NK subsets, CD56bright CD16- NK cells were significantly higher in the colon of post-COVID subjects. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p= 0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). Conclusion: Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long-term sequelae of COVID-19, including long-haul COVID.(Table Presented)(Figure Presented)