Severe Ulcerative Colitis Research Articles

Antibiotics for inflammatory bowel disease: Current status.

There is abundant literature reporting about the use of antibiotics in inflammatory bowel disease (IBD), but their role in the management of IBD is not entirely clear. Diverse infectious organisms have been implicated in the pathogenesis of Crohn's disease. Also, infections are believed to be a trigger for flares of ulcerative colitis. The benefit of the routine use of antibiotics in IBD is equivocal. However, there are certain situations, where antibiotics have a clear role and evidence of benefit: perianal fistula, intra-abdominalabscesses in Crohn's disease, acute pouchitis and infection-related flares. However, there is a lack of supportive evidence for the routine use of antibiotics in all disease-related flares. Evidence indicates a lack of benefit of intravenous antibiotics in acute severe ulcerative colitis and only limited benefit in active ulcerative colitis. Limited evidence suggests the role of a combination of oral antibiotics in pediatric ulcerative colitis. Certain targeted antibiotic regimens have been used in IBD. In ulcerative colitis, limited evidence suggests the benefit of the use of an antibiotic cocktail directed against Fusobacterium varium. Therapy directed against Escherichia coli does not seem to have a benefit in inflammatory Crohn's disease. In Crohn's disease, antimycobacterial therapy may result in symptomatic improvement but no durable benefit. Antitubercular therapy (ATT), on the contrary, may result in fibrotic transformation, suggesting a need to avoid misdiagnosis and limit the duration of ATT in Crohn's disease. This review assesses the published literature with respect to antibiotic use and provides guidance to clinicians in appropriate antibiotic use in various situations in the setting of IBD.

Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial

IntroductionSymptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk...

Intestinal barrier biomarkers in clinical evaluation of patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (P < 0.001) and severe ulcerative colitis (UC) (P < 0.0001) and active Crohn's disease (CD) (P < 0.001). In UC in remission, LBP was less than in active disease (P = 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (P = 0.030) and as severe UC was brought into remission at weeks 2 and 12 (P ≤ 0.022). Response to treatment was associated with higher baseline levels of LBP (P = 0.019) and soluble-CD14 (P = 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.

Evaluation of the Factors Associated with Post-Operative Outcome in Patients of Ulcerative Colitis Undergoing Ileal Pouchanal Anastomosis with Comparison of Functional Outcome between Stapler and Hand-Sewn Anastomosis

ntroduction Ulcerative colitis defined as a non-granulomatous idiopathic inflammatory disease which mainly affects the colon and rectum. The disease may arise at any age but most commonly affects the adults between the age group of 30–40 years.1,2. The etiology of the disease is multifactorial, involving genetic predisposition, dysregulated immune responses, epithelial barrier defects and environmental factors. No sex predilection is seen in ulcerative colitis.3,5 The peak age of onset of disease is between 30 to 40 years.4,6 The environmental factors has also been found to play an important role in the etiopathogenesis of ulcerative colitis. Cigarette smoking is one of the major factor associated with ulcerative colitis, non-smokers have a milder disease course and active smokers are less likely to develop ulcerative colitis7 Appendectomy also confers a protective effect against ulcerative colitis, especially in young patients operated for acute appendicitis.8. Classic findings in endoscopy in patients with ulcerative colitis include loss of normal vascular pattern, erythema, erosions, granularity, friability, ulcerations and bleeding9 . The primary aim of medical management is to induce and maintain remission with the long-term goals of improving quality of life and prevent disability. Absolute indications for surgery include uncontrolled hemorrhage, perforation, and colorectal carcinoma or dysplastic lesions not amenable to endoscopic removal.10 Surgery is also indicated in refractory acute severe ulcerative colitis or medically refractory disease. The most commonly performed surgery for ulcerative colitis is restorative proctocolectomy with ileal pouchanal anastomosis (IPAA). An important aspect of the surgery is the use of either sutures or staplers for anastomosis. Two types of ileal pouch-anal anastomosis (IPAA) have been described: a mucosectomy of the rectal stump followed by a hand-sewn ileal pouch-anal anastomosis.11 The alternative technique is to retain the mucosa of the rectal stump and perform a stapled pouch-anal anastomosis.

Клинический случай тяжелого течения геморрагического васкулита

Diagnosis of systemic vasculitis often causes difficulties in clinical practice. A clinical case characterized by multiple organ and comorbid pathology is presented. The manifestation of intestinal bleeding was the reason for the diagnosis of severe ulcerative colitis. The appearance of a characteristic hemorrhagic rash, followed by renal pathology with hematuria and severe nephrotic syndrome, made it possible to establish the correct diagnosis.

Medical treatment selection and outcomes for hospitalized patients with severe ulcerative colitis as defined by the Japanese criteria.

Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove-Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria. Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis. Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002-0.198), higher PRO2 (OR 0.306; 95% CI 0.144-0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019-1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853-0.995) was a negative factor to predict surgery within 28days. Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

HIGH COPY NUMBER POLYMORPHISMS OF ALPHA DEFENSIN 1-3 ARE ASSOCIATED WITH THERAPEUTIC RESPONSIVENESS IN INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND AND PURPOSE Prednisolone therapy is the first choice for the treatment of acute severe ulcerative colitis (ASUC), however, the refractory case is sometimes observed. Alpha defensin 1-3 (DEFA1A3) stored in neutrophils acts as an effector factor of innate immunity. It has been reported that the copy number variation of the DEFA1A3 gene is associated with the severity of ulcerative colitis (UC). However, the impact of DEFA1A3 in response to treatment have not been fully investigated. Therefore, we aimed to clarify the relationship between the number of DEFA1A3 copies and UC prednisolone treatment response. SUBJECTS AND METHODS Patients with UC who had attended our department and related facilities and had the number of DEFA1A3 copies measured were included between 2020 and 2022. The number of DEFA1A3 copies were measured using droplet digital PCR after DNA extraction from peripheral blood mononuclear cells. Mayo score was used to determine the response to prednisolone and severity of UC. ASUC was defined as presence of more than 6 bloody stools/d along with any one of the following: pulse rate&amp;gt; 90 bpm, temperature &amp;gt; 37.8 °C, hemoglobin &amp;lt; 10.5 g/dL, and/or CRP &amp;gt; 30mg/L. Clinical background and various parameters were extracted from medical record information. RESULTS The 47 ASUC patients were included in the study. The median DEFA1A3 copy number of the patients was 9, the median DEFA1A3 copy number in ASUC was higher than that in healthy subjects. The DEFA1A3 copy number was significantly higher in the non-remission group than in the remission group after treatment with prednisolone.There were no differences in other parameters such as CRP and WBC between the two groups. CONCLUSION DEFA1A3 copy number may be a predictive marker of prednisolone treatment response.

UPADACITINIB AS SECOND- AND THIRD-LINE SALVAGE THERAPY FOR REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS

Abstract INTRODUCTION Intravenous (IV) corticosteroids (CS) remain first line therapy for acute severe ulcerative colitis (ASUC). Up to 40% are CS refractory. Prior biologic exposure, colonic drug loss and systemic toxicities limit their utility. Colectomy rates remain up to 30% in CS refractory cases emphasizing the need for expanding alternative strategies. We report our experience of upadacitinib (UPA) as 2nd and 3rd line salvage in refractory ASUC. METHODS ASUC was defined by Truelove and Witts’ criteria. Travis index was used to assess 3-day response to inpatient (IP) therapies. IP therapeutic non-response was defined as ≥ 8 bowel movements (BM)/day or &amp;gt; 2 BM and CRP &amp;gt; 45 mg/L. IP response was defined as ≤ 4 BM and CRP &amp;lt; 45 mg/L. Primary outcome include response to IP UPA salvage at day 3 and colectomy by week (WK) 16. Patients (pts) undergoing colectomy were followed until time to event. Secondary outcomes include post-discharge clinical and biochemical remission, clinical response and rate of adverse events at WK 8/16. Clinical remission/response was defined by STRIDE-2 guidelines using partial mayo (PM). Biochemical remission was defined as fecal calprotectin (FC) &amp;lt;250 ug/g or CRP &amp;lt;5 mg/L. No cardiovascular, thromboembolic or non-HSV infections were seen. RESULTS Four ASUC pts failing IV CS required inpatient UPA salvage (Table 1). At baseline, all pts had severe pancolonic endoscopic disease (median total mayo 11, median PM 9). Median exposure to prior advanced therapies was 4. Baseline median FC was 3000 ug/g and CRP 167 mg/dL. Pt #1, #2 received UPA as 2nd line salvage due to prior IFX failure (Table 2). Pts #3, #4 received UPA as 3rd line salvage due to IFX failure at index admission (IA). One received UPA 45 mg QD (pt #1) and three received 30 mg BID (pts #2-4). All pts achieved IP response to UPA. No pts needed colectomy at IA. Overall median length of hospital stay was 14 days. Median time to UPA response was 2.5 days. Discharge time post-UPA was 3.5 days. At WK 8, pt #1 attained response with resolution of rectal bleeding (RB), BM (-85%), CRP (-91%), FC (-82%), and PM 3 (Table 3-4). At WK 16, pt #1 met criteria for clinical and biochemical remission with PM 1, normal FC (-95%) and CRP (-98%). Pt #1,#3 achieved complete steroid taper and avoided colectomy over 16 WK. Pt #2 failed CS taper and had colectomy on day 33. Pt #3 achieved clinical and biochemical remission with PM 1 and CRP 5 mg/dL (-94%) at WK 8. At WK 16, pt #3 sustained CS free clinical and biochemical remission with normalized BM (-93%), FC (-92%), CRP (-98%) and sustained resolution of RB. Assessment of pt #4 was limited to IP UPA response pending follow up. Outcomes were similar in pts receiving UPA as 2nd and 3rd line salvage. CONCLUSION We report efficacy and safety of UPA as 2nd and 3rd line salvage for ASUC thus expanding the armamentarium for medical salvage therapy. Table 1 Baseline Disease Characteristics Table 2 Patient Specific Inpatient Therapy Table 3 Comparison of Disease Activity Parameters at Baseline, Discharge, 8 Weeks and 16 Weeks Table 4 Percentage Difference of Disease Activity Parameters at Discharge, 8 Weeks and 16 Weeks in Comparison to Baseline

P673 Accelerated intravenous ustekinumab dosing as rescue therapy in Moderate- Severe Ulcerative Colitis

Abstract Background Ustekinumab (UST) is an accepted treatment for patients with moderate- severe Ulcerative Colitis (UC) following failure with corticosteroids and/or anti-TNF. Some studies suggest that intravenous (IV) administration, in an accelerated schedule, could improve outcomes in this difficult-to-manage group with a high risk of colectomy. Methods We conducted a retrospective analysis in patients with moderate-severe UC who received UST (IV) as rescue treatment, following failure with corticosteroids and infliximab. UST was administered intravenously, with an initial dose of 6mg/Kg followed by 130mg every four weeks. Clinical activity was determined by the Partial Mayo Score (PMS), and endoscopic activity by the Mayo Score (SM). Clinical Remission (CR) was defined as PMS&amp;lt;2, and Clinical Response (CRp) as a reduction in activity of ≥30%. Results The study included 17 patients, 8 (47%) women, 9 (52.9%) of whom were hospitalized at baseline, and 11/17 required transfusion or intravenous iron. According to PMS, clinical activity was severe in 16 (94.12%) and moderate in one. Endoscopic activity according to SM was severe in 13 (76.4%). Clinical remission and response were as follows: 1 (5.8%) / 7 (41.1%) patients respectively at week 4; 8 (47%) / 16 (94.1%) patients at week 12; and at week 26, 15 patients had completed the study, 10 (66.6%) in CR, and 12 (80%) in CRp. Ustekinumab was withdrawn in one case due to an infusion reaction, and one patient underwent colectomy. No independent predictors of response to UST were found in this study. Conclusion Intravenous ustekinumab in an accelerated dosing schedule is effective in moderate-severe UC, achieving clinical response in more than two-thirds of patients at week 26.

P711 Outcomes of Outpatient Biologic Exposed Patients Hospitalized with Severe Ulcerative Colitis

Abstract Background Up to 20% of patients with ulcerative colitis (UC) will require hospitalization for an acute severe flare. It is unclear whether outpatient exposure to biologics alters the outcomes of inpatient severe UC. We aimed to assess the outcomes of hospitalized severe UC patients exposed to biologics in the outpatient setting. Methods This was a multicenter, retrospective study of adult patients hospitalized with severe UC at University of Cambridge, Cambridge, St. Mark’s Hospital, London and Yale University, Connecticut (from 1/1/2012-11/1/2021). We included adult patients (age ≥ 18 years) who were hospitalized for a severe UC flare as determined by the treating clinician. The primary outcome was need for colectomy among outpatient biologic exposed vs biologic naïve patients. Secondary outcomes stratified by outpatient biologic exposure included length of hospitalization and need for rescue medical therapy. Results A total of 382 patients (53.2% male) with a median age of 35 years [interquartile range (IQR) 25-53] were reviewed. Outpatient biologic exposure was noted in 23.2% (n=86, 52 exposed to infliximab) while 76.8% (n=284) were naïve to biologics. Median disease duration was longer in the biologic exposed group at 6 years (IQR 2-11) compared to 2 years (IQR 1-8) in the biologic naïve group (p &amp;lt; 0.001). Biologic exposed group was more likely to have pancolitis (70.2% vs. 54.7%; p=0.04). The C-reactive protein (CRP) to albumin ratio was higher in the biologic naïve group was higher at 12.8 (IQR: 3.2-35) vs. 8 (IQR: 1-21.5) (p=0.004). The biologic exposed group was more likely to undergo colectomy at 25% (n=21) vs. 9.3% (n=26) in the biologic naïve group (p&amp;lt;0.001). The median hospital length of stay was 6 days (IQR: 4-9) in both groups (p=0.96). Need for rescue medical therapy 37.7% (n=107) in the biologic naïve group vs. 41.9% (n=36) in the biologic exposed group (p=0.49). Colectomy was associated with outpatient biologic exposure (44.7% vs. 19.9%, p=0.0002), Mayo UC endoscopic sub-score of 3 (81.6% vs. 55.1%, p=0.002), higher median CRP [70.6 (IQR:26.8-126.3) vs. 38.8 mg/dL (IQR: 9.7-94.7), p=0.04], lower median albumin [3 (IQR: 2.7-3.6) vs. 3.5 (IQR: 3-4) g/dL, p=0.0002], and female sex (61.2% vs. 44.8%, p=0.03). On multivariable analysis, only low albumin was independently associated with risk of colectomy (odds ratio: 3.31, 95% confidence interval 1.59-6.87, p=0.0005) Conclusion In our multicenter cohort, outpatient biologic exposure was associated with increased risk of colectomy among hospitalized patients with severe UC but on multivariable analysis only low albumin was independently associated with risk of colectomy. Further study of larger cohorts is warranted.

P951 Efficacy and safety of tofacitinib for the treatment of moderate- severe ulcerative colitis in biologic naïve patients

Abstract Background To assess the rates of clinical response at week 8, biochemical response, steroid-free clinical remission, endoscopic healing and safety data at week 26 of tofacitinib in biologic naive patients with moderate-severe ulcerative colitis (UC). Methods This was a retrospective analysis of prospectively collected data extracted from the notes of biologic naïve patients with moderate-severe UC who were treated with tofacitinib in the last 3 years in 5 Greek IBD centers and who had a follow up of at least 26 weeks after initiation of treatment. Tofacitinib was administered at a dose of 10 mg bid for 8 or 16 weeks followed by a maintenance dose of 5mg bid thereafter. Week-8 or -16 clinical response was defined as the reduction in the partial Mayo score of at least 2 points, without concomitant use of any steroid preparation [budesonide, prednis(ol)one, or methylprednisolone]. Steroid free clinical remission at week 26 was defined as a partial Mayo score of ≤1 points without concomitant use of any steroid preparation. Biochemical response at week 26 was defined as any reduction in fecal calprotectin or plasma C-reactive protein concentrations as compared to their baseline levels.Mucosal healing at week 26 was defined as Mayo endoscopic sub-score of ≤1. A safety list of all reported adverse events was completed. Treatment discontinuation due to adverse events was considered as treatment failure, whereas patients needing escalation of the maintenance dose were also considered as non-responders. Results Overall, 41 patients (26 males), aged (mean, SD) 35.2 (12.7) years and disease duration of mean (SD) 6.5 (4.8) years were included. UC was extensive in 22, left-sided in 17, and proctitis in 2 patients. Clinical response was seen in 31 (75.6%) and 34 (82.9%) patients at week 8 and 12 respectively.Biochemical response and steroid free clinical remission at week 26 were seen in 35 (85.4%) patients. Endoscopic healing was seen in 29 (70.7%) patients. Adverse events,which did not lead to treatment discontinuation, occurred in 5 patients (hyperlipidemia n=3, elevated liver enzymesn=1, herpes zoster n=1). Conclusion In this retrospective real-world ongoing cohort study, tofacitinib demonstrated clinical response at week 8 or 16 and steroid free clinical remission at week 26 in more than 75% of biologic naïve patients with moderate-severe UC with a good safety profile.

P204 Utility of Rotational Thrombo-Elastometry as an Objective Measure of Hypercoagulability in Patients with Ulcerative Colitis-A Prospective Case Control Study

Abstract Background Inflammatory bowel disease (IBD) has an increased risk of venous thromboembolism (VTE) with factors like hospitalization and surgery increasing this risk. Although few recent guidelines recommend anticoagulation thromboprophylaxis for hospitalised IBD patients, there is wide variation in reported practices for VTE prophylaxis. This study was aimed to evaluate Rotational Thrombo-Elastometry (ROTEM) for assessing blood coagulation status in ulcerative colitis (UC) and to evaluate the relationship between ROTEM, disease severity and response to treatment. Methods This was a prospective age- and sex-matched study with 60 patients each in UC and irritable bowel syndrome (IBS) groups, latter being controls. Clinical details, blood investigations including ROTEM and D-dimer were collected and analysed after taking informed consent. Hypercoagulable state was defined using Kaufmann’s classification. ROTEM parameters [clotting time (CT), clot formation time (CFT), alpha angle (AA), maximum clot firmness (MCF), maximum lysis (ML)] and D-dimer levels were compared between the two groups. Results Of the 60 UC patients (age: 38.6±11.64 years, 44 males); 15(25%) were in remission, 18(30%), 17(28.3%) and 10(16.7%) had mild, moderate, and severe disease respectively. The UC group had significantly more hypercoagulable ROTEM than the control group (66.7% vs. 36.7%, p=0.001). Hypercoagulable ROTEM was found in 9(60%), 8(44.4%), 14(82.3%) and 9(90%) of those in remission, with mild, moderate and severe UC respectively. Compared to controls; CT [292.36±70.45 vs 337.56±77.89, p=0.001], CFT [103.15±30.31 vs 128.61±40.18, p=0.0001], AA [69.88±5.19 vs 65.36±6.4, p=0.00004], MCF [65.75±5.64 vs 63.25±4.43, p=0.008] and D-dimer levels [329(63-2358) vs 145.5(54-1304), p=0.00001) were significantly abnormal in UC group. Among UC patients with mild, moderate and severe disease; only CFT, AA and D-dimer were significantly different between the groups. There was no significant difference in ROTEM values and D-dimer level in patients with severe UC after one week of treatment. On univariate analysis; partial Mayo score [OR: 1.49, 95% CI: 1.04-2.12, p=0.028], serum albumin [OR: 0.32, 95% CI: 0.10-0.98, p=0.04], hemoglobin [OR: 0.59, 95% CI: 0.40-0.86, p=0.007], and platelets [OR: 1, 95% CI: 1.01-1.02, p=0.035], were predictors of hypercoagulable state in active UC. On multivariate analysis; only haemoglobin [OR: 0.61, 95% CI: 0.38-0.98, p=0.04] was found to be significant independent predictor. Conclusion UC patients had hypercoagulable ROTEM regardless of activity of inflammatory process. The degree of hypercoagulability increased with disease activity. Low haemoglobin was found to predictive of hypercoagulable state in active UC patients.

P298 Adherence to diagnostic and treatment recommendations for the management of acute severe ulcerative colitis: a prospective and multinational study

Abstract Background Acute severe ulcerative colitis (ASUC) is a serious, potentially life-threatening condition. Hospital admission and prompt medical therapy with intravenous steroids is crucial, but rescue medical therapy is frequently needed, and surgery is often required. Our aim was to assess the adherence to main diagnostic and management recommendations within the MASC multinational study. Methods MASC was a prospective, multinational cohort study, including all consecutive patients hospitalized for ASUC between February 2019-January 2020. The primary outcome was surgery during the first 90 days after admission. We used descriptive statistics to determine the proportion of patients fulfilling each diagnostic and treatment recommendation according to ECCO and AGA. Results A total of 823 patients from 123 centers in 32 countries in five continents were included (median age 39 years [IQR, 28-54], 56% male, 64% non-smokers; Table 1). Most cases (74%) had a previous diagnosis of ulcerative colitis, and around half (48%) with prior ASUC episodes. Upon admission, they were under 5-ASA therapy (60%), thiopurines (14%), or biologics (21%). They were mostly admitted to the Gastroenterology ward (74%). During the initial assessment, 112 patients (15%) did not have stool culture or C. difficile testing, and CMV was evaluated in 50% of cases. Endoscopic assessment was performed in 66% of patients, mainly by flexible rectosigmoidoscopy (74%). Regarding treatment, 3.4% of patients received exclusive parenteral nutrition, 70% low molecular weight heparin, and 42% prophylactic antibiotics (Table 2). Steroids were started after a median of 0 days (IQR, 0-1), mostly with methylprednisolone or hydrocortisone (64%), 26% with other steroids, and 7% were managed without steroids. Infliximab was started in 159 patients (19%) after a median of 6 days (IQR, 4-8) after starting steroids, with 27% after &amp;gt;7 days. Most of the patients (93%) had some type of tuberculosis screening done prior to infliximab. Twenty-eight patients (3.4%) started cyclosporine. Thirty-two patients (4%) received other rescue therapy different from infliximab or cyclosporin. Colectomy was performed in 25 patients (3%). Conclusion The diagnostic and medical management of ASUC remains heterogeneous and different from current recommendations. This context demands more evidence and consensus on the best management of ASUC.

P891 Comparative Effectiveness and Safety of Infliximab and Tacrolimus in the Treatment of Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) affects approximately 20% of patients with ulcerative colitis (UC). Patients failing initial corticosteroid therapy receive salvage therapy with either infliximab (IFX) or calcineurin inhibitors, cyclosporine (CYS) or tacrolimus (TAC). We aimed to compare the effectiveness and safety of IFX and the oral calcineurin inhibitor, TAC, in this setting. Methods This retrospective cohort study included consecutive patients with ASUC, based on the Truelove and Witts criteria, admitted to Tel Aviv Medical Center between 2017 and 2022 and treated with salvage therapy. Demographic, clinical, and laboratory data were retrieved. The primary endpoint was successful salvage therapy defined as clinical response resulting in discharge without colectomy. Secondary endpoints included the colectomy rates at 90 days and the safety profile of the treatments. Results During the study period 96 patients with ASUC were admitted to our center. Of these, 40 patients received salvage therapy – 21 patients received IFX and 16 received TAC and were included in the analysis; 3 patients received CYS and were excluded from the study. Demographic data are detailed in Table 1. Disease duration was significantly longer in patients receiving TAC (mean (±SD) 9.7 years (±7.1) vs 4.5 (±5.9), p=0.04). In addition, patients receiving TAC had significantly greater prior exposure to advanced therapies (14 (87.5%) vs 6 (28.6%), p&amp;lt;0.001) and 12 (75%) patients had previous exposure to IFX. Baseline markers of disease severity including disease extent, hemoglobin, C-reactive protein (CRP), albumin and body mass index (BMI) were similar between the treatment groups (Table 1). Therapeutic success was similar between treatment groups (IFX: 18 (86%) vs TAC: 15 (94%), p=0.62). The 90-day colectomy rate (IFX: 4 (19%) vs TAC: 2 (12.5%), p=0.68), CRP upon discharge (median (IQR) IFX: 15 mg/L (3.3-27) vs TAC: 11 mg/L (5.4-25, p=0.64) and length of hospitalization (mean (±SD) IFX: 23.5 days (±19.46) vs TAC: 17.56 days (±5), p=0.19) were similar between the groups. Safety profiles were similar between the treatment groups with mild electrolyte disturbances treated conservatively in both groups and no observed infections, deaths or other adverse events. Conclusion This real world, retrospective study shows that IFX and TAC have similar effectiveness and safety in the setting of ASUC. In this study, patients receiving TAC had significantly longer disease duration and advanced therapy exposure than those receiving IFX and still maintained excellent effectiveness highlighting TAC’s value in this setting.

P664 Anti-TNF exposure is associated with an increased risk of urgent and one-year colectomy in Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is significantly associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains clinically challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC. Methods A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Patients with well-documented data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed. Multivariable logistic regression analyses were performed to identify clinical, biochemical, and endoscopic parameters associated with colectomy risk in patients with ASUC. Results Out of the 158 patients included, 34 (21.5%) underwent colectomy during hospital admission, and 41 (25.9%) within one year after admission. On multivariable analysis, adjusting for age, sex, body mass index (BMI), and disease duration, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P=0.005) and the use of biologics (any type) at admission (OR 3.31, 95%CI: 1.14-9.63, P=0.028) were associated with an increased risk of 1-year colectomy. Conversely, the use of mesalamines at admission was associated with a decreased risk of 1-year colectomy (OR 0.31, 95%CI: [0.13-0.72], P=0.006). Furthermore, recent UC-related hospitalization (within one year of admission) (OR 2.72, 95%CI: 1.15-6.43, P=0.022) and increased number of bowel movements after 3 days of treatment (OR 1.18, 95%CI: 1.04-1.34, P=0.011) were associated with higher risk of 1-year colectomy. Biomarkers measured at admission including hemoglobin and albumin were associated with a decreased risk, while CRP was associated with an increased risk of urgent and 1-year colectomy. Patients with deep ulcerations observed at endoscopy tended to have an increased risk of urgent colectomy, although this was not statistically significant (univariable OR 3.36, P=0.081). Finally, treatment of ASUC with anti-TNF was strongly associated with a decreased risk of urgent (OR 0.30, 95%CI: 0.13-0.73, P=0.007) and 1-year colectomy (OR 0.31, 95%CI: 0.14-0.73, P=0.007). Conclusion In patients with ASUC, anti-TNF treatment is associated with a reduced risk of both urgent and 1-year colectomy. Conversely a history of anti-TNF exposure is linked to a higher risk of both urgent and 1-year colectomy. This data emphasizes the need for alternative therapies.

P1001 Predictive factors of colectomy in patients admitted with Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) is a life-threatening condition which requires quick decision making and urgent treatment. To facilitate this process, it is essential to identify patients at a high risk of emergency colectomy. The aim of this study is to identify predictors for emergency colectomy in patients with ASUC. Methods A retrospective study of 121 patients admitted with ASUC to a single gastroenterology centre between 2010 and 2020 was performed. Clinical and demographic data, laboratory and endoscopic examinations results were analysed as potential predictors of colectomy. Albumin and C-reactive protein (CRP) levels were recorded at baseline and at the 3rd day after intravenous steroids (IVS) initiation. Results 119 patients initially received IVS, while 2 patients with suspected intestinal perforation underwent emergency colectomy on the first day. 64 (53%) were women, with a median age of all patients of 33 (IQR 27-49) yrs. 15 (12.4%) patients admitted with ASUC underwent colectomy, while mortality rate during hospitalization was 1.7%. During the entire follow-up period, with a median duration of 46.5 months (23-88.25), colectomy was performed in 19 (15.7%) patients. Overall, in the study group, colectomy rate at 1 month, 3 months and 2 years were 12.4%, 12.4%, and 14.0%, respectively. Assessing further outcomes after colectomy, during the follow-up period, 13 (68.4%) achieved clinical remission, 1 died during the operation, and 5 (26.3%) patients still have an active course of the disease requiring immunosuppressive treatment. When comparing patients in the colectomy group (n=13) with patients who avoided colectomy during this hospitalization (n=105), no significant differences were found in age, sex, duration of illness, body mass index, endoscopic activity, the use of prednisolone or azathioprine prior to admission or previous treatment with biologics. The presence of cytomegalovirus and Clostridium difficile infection was also not associated with a higher risk of colectomy. Significant differences between the groups were found comparing the laboratory findings: the strongest predictor of colectomy was the CRP/albumin ratio at day 3 after IVS initiation (median value was 1.26 (0,81-3,26) in colectomy group vs. 0,64 (0,25-1,36) in non-colectomy group, p&amp;lt;0.001). The difference was also observed when comparing albumin (median 26 (24-28) vs. 29 (27-32), p=0.012) and CRP (median 33 (25-83) vs. 16 (8-37), p=0.003) levels separately on the 3rd day, while at baseline there was no significant differences in laboratory findings. Conclusion A low serum albumin level, higher CRP and CRP/albumin ratio are predictive factors of emergency colectomy in ASUC patients.

P644 Body composition does not predict clinical course in patients with acute severe ulcerative colitis

Abstract Background Acute Severe Ulcerative Colitis (ASUC) is a life-threatening complication of UC. Previous research has shown that body composition parameters, including sarcopaenia, are associated with outcomes in IBD. However, the relationship between body composition and the clinical outcomes of patients hospitalised with ASUC has not yet been clearly defined. We sought to further evaluate the prognostic role of body composition and further explore predictors of clinical outcome in ASUC. Methods We performed a cohort study of hospitalised ASUC patients. Body composition was assessed using fat and muscle segmentation, at the level of the L3 vertebral body, in patients who underwent abdominal computed tomography (CT) during hospitalisation. We defined sarcopenia according to skeletal muscle index (SMI) &amp;lt; 38 cm2/m2 in females and &amp;lt; 42 cm2/m2 in males. Clinical endpoints included length of hospitalisation, need for rescue medical therapy or colectomy. Between group comparisons were performed and logistic regression was used for risk factor analysis. Results We studied 116 patients with ASUC, 51 of whom underwent abdominal CT imaging during their hospitalisation. Median age was 32 years and 64% of patients were female. Sixty-two patients (53.5%) required rescue medical therapy. Rescue medical therapy was successful in 48 patients (77.4%) and 14 patients (22.6%) required an inpatient colectomy. Patients who underwent CT imaging during admission required increased rescue medical therapy (66.7% vs 43.1%, p=0.02) and were hospitalised for longer (11 vs 6 days, p&amp;lt;0.001). Compared to non-sarcopaenic patients, sarcopaenic patients did not require increased rescue medical therapy (60.7 % vs 79 %, p= 0.22) nor longer median hospitalisation (10.5 vs 11.4 days, p=0.69). We observed a trend towards increased rescue therapy failure in patients with sarcopaenia (52.9% vs 33.3%, p=0.31). Higher Mayo score at presentation was associated with increased need for rescue medical therapy (OR 2.18, 95%CI: 1.43-3.33, p&amp;lt;0.001) and an increasing C-reactive protein (CRP) to albumin ratio predicted prolonged length of stay (OR 1.44, 95%CI: 1.18-1.77, p=&amp;lt;0.001). Conclusion Sarcopaenia did not predict ASUC outcomes in this cohort. Higher Mayo score and increased CRP to albumin ratio at admission predicted prolonged hospitalisation and need for rescue medical therapy.

P830 The potential role of artificial intelligence in selecting the modality of biological therapy in patients with inflammatory bowel disease

Abstract Background Selecting an appropriate treatment strategy for inflammatory bowel disease (IBD) is an important task that can significantly alter the clinical course of the disease. Advanced artificial intelligence language models, such as ChatGPT, represent a potential future option that can assist practitioners. ChatGPT can help search the internet for medical facts by summarizing information from medical sources and providing concise explanations, simplifying the process of accessing and understanding medical information. Methods A ChatGPT-guided analysis of 89 IBD patients treated at the Clinical Department of Gastroenterology and Hepatology at University Medical Center "Zvezdara", Belgrade was conducted, considering further treatment with some biological drugs. A treatment modality proposal was obtained through communication with the interactive software ChatGPT (OpenAI, CA USA) and providing complete clinical and laboratory data. The alignment of decisions was analyzed, along with an assessment of treatment success in the group with matching and differing choices. Results In 72 patients (81%), there was concordance in the choice of therapy between ChatGPT and the medical consultation, while in 17 patients, ideas about the treatment approach differed. The most common difference in the choice of therapeutic modality related to the software's selection of ustekinumab compared to our choice of vedolizumab in patients with Crohn's disease who were not biologically naive, affecting seven patients with these characteristics. In 4 patients with severe ulcerative colitis, ChatGPT recommended using cyclosporine in combination with vedolizumab, contrary to the medical consultation's decision to use Anti-TNFα therapy. The group of patients in whom the artificial intelligence advice differed from the medical consultation was in a clinically more severe stage of the disease (CRP 10.4 vs. 9.1, p=0.0293), with worse endoscopic findings (proportion of severe endoscopic disease SES CD≥33/Mayo score&amp;gt;2, 53% vs. 24%, p=0.019). Taking into account the baseline differences in these patient groups, multiple analyses of covariance did not reveal a significant difference in the ultimate treatment outcome - proportions of endoscopic (p=0.773) and clinical remission (p=0.296) between patient groups. Conclusion The integration of advanced artificial intelligence language models may represent a future tactic with the potential to assist practitioners in making decisions about the treatment modality for IBD patients, but clinical experience should be considered.

P336 Exploring Extracellular Matrix Markers in Ulcerative Colitis: Degradation and Formation Insights

Abstract Background The gold standard for assessing disease activity in ulcerative colitis (UC) is endoscopy, which is uncomfortable for the patient, and only evaluates the superficial layers of the colon. Intestinal extracellular matrix (ECM) remodeling is highly dynamic during disease activity and blood spillover of ECM components might reflect transmural disease burden. The aim of this study was to evaluate baseline serum markers of ECM formation (PRO-C11, PRO-C22, and PRO-C7) and degradation (C7M) to assess disease activity and treatment response in UC. Methods Forty-nine UC patients with active disease and 50 healthy controls (HC) were included. All underwent endoscopy and blood sampling at inclusion. UC patients additionally had fecal calprotectin (FCP) measured at baseline and had treatment adjusted at the discretion of the attending physician. Subsequent follow up of UC patients included clinical activity score, FCP, and blood samples at 3 and 6 months as well as an endoscopy at 6 months. Ulcerative Colitis Endoscopic Index of Severity (UCEIS), total Mayo score (TMS), and disease extent (E1-E3) was registered. Response was defined as a reduction from severe to moderate or mild disease based on TMS. If no follow-up endoscopy was performed (n=9), partial Mayo was used. Spearman’s correlation and one-way-ANOVA with Turkey correlation and correction for multiple testing were applied for statistical analysis. Results All markers of ECM degradation and formation were elevated in patients with severely active UC measured by both UCEIS and TMS compared to HC (adjusted p&amp;lt;0.0001 for each marker). CM7 and PRO-C22 differentiated moderate from severe UC by TMS (p&amp;lt;0.0001) and UCEIS (p&amp;lt;0.05) (Figure 1A-B). Baseline C7M, PRO-C7, and PRO-C11 correlated with CRP (Spearman’s: r=0.82, p&amp;lt;0.0001; r=-0.45, p=0.0012; and r=-0.33, p=0.032, respectively). None of the markers correlated with FCP. Elevated C7M, PRO-C7, and PRO-C11 levels for E3 could differentiate E3 from E1 (Difference ng/ml: 3.89 (SE of diff: 1.47), 13.15 (4.55), 10.08 (4.09), respectively, all p&amp;lt;0.05) (Figure 1C-E). Remission was achieved in 18/49 patients at 6 months. Both C7M and PRO-22 exhibited acceptable discriminative capabilities at baseline for 6-month TMS between remission and non-remission (AUC 0.72 (95% CI 0.58-0.87) p=0.01 and AUC 0.68 (95% CI 0.53-0.83) p=0.04, respectively) (Figure 1F-G). Conclusion This study demonstrates that ECM markers correlate with disease activity, disease extent, and predict future disease outcome in UC. ECM markers hold great promise as they provide a 'window' into transmural tissue remodeling and inflammatory and fibrotic burden, warranting further investigation.