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Acute severe ulcerative colitis is a medical emergency requiring inpatient treatment with intravenous steroids. Approximately one-third of patients do not respond to steroids sufficiently and require medical rescue therapy. Infliximab and cyclosporine are equally effective rescue agents, though infliximab is often preferred by clinicians for ease of use and greater familiarity. The use of cyclosporine is becoming more frequent, however, in patients previously exposed to infliximab. Those patients not exhibiting an adequate response to rescue therapy require colectomy. There is increasing interest in modified medical treatment to rescue the need for surgery. Janus kinase inhibitors may provide benefits when used alongside steroids from admission or as a rescue agent, but further randomised trials are needed to clearly establish their role. Intensified dosing of infliximab when used as a rescue therapy has shown mixed results but seems sensible in patients with low albumin and high disease burden. In this review, we describe the current established treatment pathways and report newer developments and evolving concepts that may in the future improve the care of patients with acute severe ulcerative colitis. [ABSTRACT FROM AUTHOR]

• Aside from absolute emergencies for which surgical intervention is obviously required, the overwhelming majority of indications for surgery necessitates multidisciplinary discussion in a center specialized in inflammatory bowel disease, the reason being that multiple medical options may be proposed, even in non-elective situations. • In cases of refractory colitis, the choice between a new line of medical treatment and a surgical procedure is singularly complex. It is necessary to weigh chronic symptoms of the disease, which may be experienced as a burden, against the risks of complications and sequalae, subsequent to the operation. • The appearance of dysplastic lesions should be considered as a turning point in the evolution of monitored ulcerative colitis (UC). Detection of dysplastic lesions necessitates: (1) chromoendoscopy surveillance with staged biopsies of all visible lesions in the colonic framework, (2) anatomopathological verification, and (3) multidisciplinary discussion aimed at deciding on surgical or endoscopic management, which remains reserved for only a limited number of selected patients. • With regard to UC, total proctocolectomy with ileo-anal anastomosis (TCP-IAA) is the surgical treatment of reference insofar as it enables patients to be cured of the disease, while limiting functional digestive sequelae. It can be carried in one, in two modified, or in three phases. Treatment of ulcerative colitis (UC) has been revolutionized by the arrival of biotherapies and technical progress in interventional endoscopy and surgery. (Sub)total emergency colectomy is required in the event of complicated severe acute colitis: colectasis, perforation, hemorrhage, organ failure. Corticosteroid therapy is the reference treatment for uncomplicated severe acute colitis, while infliximab and ciclosporin are 2nd-line treatments. At each step, before and after each line of treatment failure, surgery should be considered as an option. In cases refractory to medical treatment, the choice between surgery and change in medication must weigh the chronic symptoms associated with the disease against the risks of postoperative complications and functional sequelae inherent to surgery. Detection of dysplastic lesions necessitates chromoendoscopic imaging with multiple biopsies and anatomopathological verification. Endoscopic treatment of these lesions remains reserved for selected patients. These different indications call for multidisciplinary medical-surgical discussion. Total coloproctectomy with ileo-anal anastomosis (TCP-IAA) is the standard surgery, and it holds out hope for healing. Modalities depend on patient characteristics, previous emergency colectomy, and presence of dysplasia. It may be carried out in one, in two modified, or in three phases. The main complications are anastomotic fistula, short-term pouch-related fistula, ileo-anal pouch syndrome, pouchitis and long-term digestive and sexual disorders. For selected cases, an alternative can consist in total colectomy with ileo-rectal anastomosis or permanent terminal ileostomy. The objective of this update is to clarify the indications, modalities, and results of surgical treatment of ulcerative colitis in accordance with the most recent data in the literature. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. Aims: We hypothesized that upadacitinib may be effective in treating acute severe colitis. Methods: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. Results: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. Conclusion: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results. [ABSTRACT FROM AUTHOR]

Acute severe colitis (ASUC) remains a significant cause of morbidity in up to 25% of patients with ulcerative colitis during their disease course. We present the outcomes out to 12 months following the use of high‐dose tofacitinib, 10 mg three times daily (TDS), in patients with steroid and infliximab refractory ASUC. A total of 11 patients with ASUC who were treated with high‐dose tofacitinib after failing sequential infliximab therapy between 2019 and 2021 were identified at an Australian tertiary centre. Ten of 11 patients demonstrated clinical and biochemical response to treatment during admission. Two of 11 patients required colectomy, one during the index admission and the other during re‐admission 10 days after the index presentation. Nine of the initial responders had a median Mayo score of 1 (IQR 0–4) at both 6 and 12 months, and all remained colectomy‐free out to 12 months. Neither venous thromboembolic events nor major infective complications were observed. Tofacitinib may be a safe and effective induction and maintenance agent in the treatment of steroid and infliximab refractory ASUC. Prospective studies with long‐term follow‐up are required to explore the use of tofacitinib in ASUC before it can be routinely recommended as salvage therapy. [ABSTRACT FROM AUTHOR]

Objectives: The PRASCO trial reported the short-term superiority of an antibiotic cocktail plus intravenous corticosteroids (IVCS) over IVCS alone in children with acute severe colitis (ASC). Here, we report the extension of the PRASCO trial and the long-term outcomes of the antibiotic cocktail in ASC., Methods: This prospective follow-up of the PRASCO trial documented disease outcomes and treatments annually through 5 years. The primary outcome was colectomy, and the secondary outcome was escalation to biologics, analyzed descriptively., Results: A total of 26 children were included (12 receiving IVCS and 14 receiving IVCS + antibiotics), 19% of whom underwent colectomy during the follow-up period. The estimated probability of colectomy at 3, 6, and 12 months from admission were 7.1%, 7.1%, and 21% with IVCS + antibiotics and 0%, 8.3%, and 17% with IVCS. No children required colectomy after the first year of follow-up. The estimated probability of escalating to biologics were 66%, 77%, and 77% after 1, 2, and 3 years with IVCS + antibiotics and 42%, 51%, and 76% with IVCS. Clinical remission was higher in the IVCS + antibiotics group at each timepoint (e.g., 30% vs. 11% at 5-years). Delta of Pediatric Ulcerative Colitis Activity Index (PUCAI) score from baseline to day three of admission predicted future escalation to biologics (area under curves (AUC) 0.84 [95%CI 0.59-1.0])., Conclusion: While adding antibiotics to IVCS may provide better short-term outcomes, the long-term benefits were comparable to IVCS alone. At 5 years, about one-fifth of children had undergone colectomy, and almost four-fifths had escalated to biologics, particularly during the first year after admission., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

A 74-year-old woman developed acute severe colitis after receiving her sixth mRNA vaccine against coronavirus disease-2019 (COVID-19). On the day after vaccination, she experienced bloody diarrhea, abdominal pain, and high-grade fever. Laboratory tests revealed leukocytosis and increased C-reactive protein. Contrast-enhanced computed tomography revealed bowel wall thickening with a reduced contrast effect within the colon, in addition to ascites. Sigmoidoscopy revealed extensive sloughing of the mucosa. Her symptoms and laboratory findings improved immediately after the initiation of prednisolone therapy. Pre-discharge total colonoscopy revealed mucosal repair in most of the colon. Clinicians should acknowledge that severe acute colitis can occur after COVID-19 vaccination.

Tofacitinib has emerged as a useful drug for the treatment of ulcerative colitis (UC). There is an unmet need for cost-effective, non-immunogenic drugs with a safe adverse effect profile to treat patients with ulcerative colitis. In the present review, we evaluate the available literature to inform the appropriate positioning of tofacitinib in the current drug landscape and identify subsets where its use should be done with caution. Tofacitinib is helpful in the treatment of patients where the standard conventional or biological therapies have failed or were not tolerated. With lower costs of the generic drug than the biologicals (or biosimilars), it could be an important therapy in low- to middle-income countries. The risk of infections, especially Herpes Zoster and tuberculosis, needs to be addressed before initiation. Tofacitinib should be avoided in patients with venous thromboembolism and cardiovascular disease risk factors. Due to limited evidence, the use is not recommended in pregnancy, while it should be used with caution in elderly citizens. Future trials should look into the head-to-head comparison of tofacitinib with biologicals. The role of tofacitinib in acute severe colitis needs evaluation with comparative trials with current standards of care. [ABSTRACT FROM AUTHOR]

Tom Holvoet,1,2 Triana Lobaton,2 Pieter Hindryckx2 1Department of Gastroenterology, AZ Nikolaas, Sint-Niklaas, Belgium; 2Department of Gastroenterology, University Hospital Ghent, Ghent, BelgiumCorrespondence: Tom Holvoet Email tom.holvoet@aznikolaas.beAbstract: Acute severe colitis is a severe complication of ulcerative colitis, affecting approximately 20% of patients. For physicians, it remains a challenging condition to treat. Current treatment algorithms have diminished the mortality associated with acute severe ulcerative colitis (ASUC), but colectomy rates remain high (approximately 30%) despite advances in therapy. Colectomy in ASUC is particularly associated with important postoperative complications and morbidity. In this review, reasons for the inability to improve care and avoid evolution to colectomy for ASUC are explored and solutions that might lead to a better management of the disease are investigated.Keywords: acute severe colitis, ulcerative colitis, inflammatory bowel disease

Copyright of Pediatrie pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In recent years, tofacitinib has been used in patients with acute severe ulcerative colitis (ASUC) as a rescue therapy with encouraging success rates. We present details of four patients with steroid-refractory ASUC treated with tofacitinib. All the patients were biologics-naive. Tofacitinib was initiated in a dose of 10 mg three times daily in three patients and 10 mg twice daily in the remaining patient. Three of the four patients improved and were discharged in clinical remission. These patients continue to be in colectomy-free and steroid-free remission on follow-up. The remaining patient did not respond to tofacitinib and required a colectomy. No adverse event related to tofacitinib use was noted in any of these four patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Committee of Chitwan Medical College issued approval CMC-IRC/080/081-059. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ranjan et al.)

Objectives: Upadacitinib (UPA), a selective Janus kinase-1 inhibitor, has demonstrated efficacy in inducing and maintaining remission in moderate to severe ulcerative colitis (UC) in adults. Current standard management for acute severe ulcerative colitis (ASUC) involves intravenous corticosteroids (IVCS) followed by infliximab (IFX) salvage therapy. Limited data exist on the utility of UPA in ASUC, particularly in adolescents. This case series reports the use of UPA as salvage therapy in hospitalized adolescents experiencing ASUC refractory to IFX., Methods: We performed a retrospective chart review of hospitalized patients with ASUC who received UPA as salvage therapy after initiation of IVCS and failure of IFX., Results: Three adolescents were hospitalized with ASUC for which IFX infusion treatments were unsuccessful. Initiation of UPA enabled patients to improve their Pediatric Ulcerative Colitis Activity Index scores to ≤35 and be discharged home. Hospitalization course, complications, and follow-up information are provided., Conclusion: UPA is a promising short-term salvage therapy in adolescent ASUC cases resistant to conventional treatments. Prospective studies are warranted to elucidate its long-term efficacy and safety in this specific population. These findings provide a novel therapeutic avenue for managing ASUC in adolescents, offering hope for those encountering treatment challenges., Competing Interests: Jeannie S. Huang has research funded by Janssen and by Abbvie but not related to this manuscript or upadacitinib. Laura E. Bauman is involved in industry sponsored clinical trials with Gilead and Albireo not related to this manuscript or upadacitinib. All funding is through the institution and is ongoing. The authors declare no conflict of interest., (© 2024 The Author(s). JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aim: Despite widespread recommendations and use of intravenous corticosteroids (IVCS) for the treatment of acute flares of ulcerative colitis and Crohn's disease, limited evidence exists comparing outcomes of the two most common regimens, intravenous methylprednisolone (IVMP) and intravenous hydrocortisone (IVHC). IVHC has stronger mineralocorticoid effects compared with IVMP and may cause higher rates of hypokalemia. We aimed to determine differences in clinical outcomes including requirement for inpatient rescue therapy, bowel resection, and rates of hypokalemia. Methods: We conducted a multicenter cohort study of all adult patients admitted with an acute flare of inflammatory bowel disease (IBD) to the three tertiary hospitals in Auckland, New Zealand, where the protocol at each institution is either IVMP 60 mg daily or IVHC 100 mg four times daily. All patients requiring IVCS between 20 June 2016 and 30 June 2018 were included. The IVCS protocol was then changed at one hospital, where further data were collected for a further 12 months from 30 January 2019 until 30 December 2019. Results: There were 359 patients, including 129 (35.9%) patients receiving IVMP and 230 (64.1%) patients receiving IVHC. IVMP treatment was associated with a greater requirement for rescue therapy than IVHC (36.4% vs 19.6%, P = 0.001; odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.64–4.75, P < 0.001), but also reduced rates of hypokalemia (55.8% vs 67.0%, P = 0.04; OR = 0.49; 95% CI, 0.30–0.81, P = 0.005). There was no difference between treatment groups for the median length of admission (5 days, interquartile range [IQR] 3–8), median duration of IVCS treatment (3 days, IQR 2–5), or bowel resection within 30 days of admission (12.4% vs 11.7%; OR = 1.04). Conclusion: For the treatment of an acute flare of IBD, treatment with IVMP results in significantly more requirement for inpatient rescue biologic or cyclosporin. In addition, it causes statistically significant less hypokalemia than IVHC, although in practice differences are negligible. [ABSTRACT FROM AUTHOR]

Acute severe ulcerative colitis [ASUC] remains a common medical emergency, with 25% of patients with ulcerative colitis experiencing at least one event in their disease course. Despite advances in medical therapy, ASUC continues to be associated with considerable morbidity and mortality, with up to 30% of patients requiring colectomy during initial admission. Our aim was to review the current controversies and recent progress in risk stratification, prediction of outcome, and personalisation of care in ASUC. We re-assess the use of Truelove and Witts' criteria, serum biomarkers, and the use of composite clinical indices in current clinical practice. We explore the potential for endoscopic prediction using defined validated indices for accurate and early prognostication, and the need to define outcome. We also consider the impact of the current COVID-19 pandemic. Finally, we discuss the current research agenda, including the application of new and emerging biomarkers coupled with multi-omics and the implications in management and optimisation of outcome. Research priorities for the prediction of outcome in acute severe colitis include the following. 1. Development of an accurate admission score to guide early medical rescue therapy or colectomy. 2. Utility of point-of-care faecal calprotectin, with determination of optimal cut-off values. 3. Role of serum and faecal infliximab levels to both predict outcome and guide accelerated infliximab dosing. 4. Role of novel biomarkers, including serum calprotectin, in predicting response to corticosteroids or rescue therapy. 5. Specific predictors of response to ciclosporin and infliximab to allow rationalisation of drug use. 6. Utility of validated endoscopic scores. 7. Utility of radiological assessment beyond use of plain abdominal X-ray. 8. The use of multiomics and machine learning to predict risk of Acute Severe Colitis in patients with Ulcerative Colitis. [ABSTRACT FROM AUTHOR]

Background and Aim: Although the gut microbiome of patients with ulcerative colitis (UC) has been characterized, no study has characterized the gut microbiome in acute severe colitis (ASC). We compared the gut microbiome of patients with UC, ASC, and healthy controls (HCs). Methods: Patients with mild to moderate UC (n = 24), ASC (n = 19 with 21 episodes) and HCs (n = 50) were recruited prospectively. A 16SrDNA amplicon approach was used to explore gut microbial diversity and taxonomic repertoires. UC was diagnosed using European Crohn's and Colitis Organization guidelines, and ASC was diagnosed using Truelove and Witts' criteria. Results: The normalized alpha diversity was significantly lower in ASC than mild–moderately active UC (P < 0.05) or HC (P < 0.001). The gut microbiome in ASC was highly unstable, as characterized by high intracohort variation (analyzed using J‐divergence measure), which was significantly greater than in UC or HC. On principal coordinate analysis, the microbiome of HC and UC were similar, with the ASC cohort being distinct from both. Comparison of ranked abundances identified four distinct clusters of genera (G1, G2, G3, and G4), with specific trends in their abundance across three groups: G1/G2A clusters had the least, whereas G3 had the highest abundance in the ASC cohort. Conclusions: Gut microbial diversity is lower in ASC than mild–moderate UC or HCs. Gut microbiome composition is increasingly unstable in ASC, with a distinct abundance of specific genera varying between HCs and ASC. Mild–moderate UC lies within the spectrum. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we evaluate the efficacy and safety of the biosimilar infliximab, CT-P13, in the treatment of inpatients with severe steroid-refractory colitis. Methods: A retrospective cohort study of adult colitis patients (UC or isolated Crohn's colitis) admitted to the University of Chicago inflammatory bowel disease inpatient service between January 2018 and December 2018 for management of severe colitis refractory to IV steroids who received CT-P13 were included in the study. Patients diagnosed with active small bowel Crohn's disease were excluded. CT-P13 was given as a single infusion of 5 to 10 mg/kg. A comprehensive review of their electronic medical records was performed, and demographic, clinical, laboratory, and endoscopic data were extracted. The primary endpoint was colectomy-free survival. Results: Twenty-one patients with severe steroid-resistant colitis were included. Twelve patients had ulcerative colitis, seven patients had a diagnosis of indeterminate colitis, and two patients had a diagnosis of Crohn's colitis. The median age was 32.2 years. The median disease duration was 4.3 years, and the median follow-up time was 5.9 months. Patients had a median CRP of 23. All patients had moderate to severe disease on endoscopy. Colectomy-free survival was 76% at 3 months and 70% at 6 months. No severe adverse events were reported in this patient cohort. Conclusion: A significant proportion of patients with severe colitis failing IV steroids responded to induction therapy with CT-P13. Colectomy-free survival rates were similar to previous randomized trials using originator infliximab as induction therapy in severe steroid-refractory colitis. [ABSTRACT FROM AUTHOR]

Background: Multiple prior studies have looked at clinical and laboratory parameters in ulcerative colitis to predict prognosis, but individual histologic features of inflammation and their prognostic significance have not been well studied. The purpose of our study was to determine whether histologic features at presentation with acute severe colitis predict colectomy in pediatric patients. Methods: Patients were identified retrospectively through the gastroenterology and pathology databases. Demographic information, duration of disease, laboratory data, endoscopic appearance at scope, and histologic features of inflammation were reviewed along with medical therapies. Patients who underwent surgery within 90 days of hospitalization were compared to those who did not. Results: Fifty patients with acute severe colitis, defined as Pediatric Ulcerative Colitis Activity Index ≥65, were included. Sixteen patients had colectomies performed within 90 days of presentation. No statistically significant difference was found between the surgery and no-surgery groups for patient age, albumin, hemoglobin, or C-reactive protein, though hemoglobin trended toward significance, P =.05. The endoscopic Mayo score and histologic features of inflammation (architectural changes, chronic inflammation, eosinophils, neutrophils within the lamina propria, neutrophils in epithelium, crypt destruction, and ulceration) were similar between groups. Conclusion: In pediatric patients presenting for hospitalization with acute severe colitis, no histologic features of inflammation predicted colectomy within 90 days. [ABSTRACT FROM AUTHOR]

Correlation between fecal calprotectin (FC) and endoscopic activity assessed by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) in acute severe colitis (ASC) patients was explored to evaluate the predictive value of FC in clinical outcomes. Seventy-one ASC patients were retrospectively evaluated. FC level within 3 days of colonoscopy was measured with ELISA. Demographic and clinical data, laboratory parameters, and medical therapy were documented, and the endoscopic severity of disease was rated by UCEIS. The end points were the rate of failed corticosteroid therapy, colectomy, and mortality. There was significant correlation between UCEIS and FC level (r=0.729, P<0.001), which was superior to CRP, ESR, and hemoglobin. FC level between endoscopic mild activity (UCEIS, 3-4) and endoscopic moderate activity (UCEIS, 5-6), and endoscopic moderate activity (UCEIS, 5-6) and endoscopic severe activity (UCEIS, 7-8) were significantly different. FC levels were associated with different outcomes (failed corticosteroid therapy or surgery); when FC >1672 µg/g, sensitivity and specificity were 80.2 and 66.7%, respectively, in prediction for colectomy using receiver operating characteristics analysis. The results indicated that FC, as a non-invasive indicator, correlates positively with the UCEIS. Baseline FC level predicts clinical outcomes in ASC patients, which make a timely treatment strategy conversion possible after accurately forecasting the likelihood of failure of intravenous steroid therapy. [ABSTRACT FROM AUTHOR]

Copyright of Gyermekgyógyászat is the property of Semmelweis Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ulcerative colitis (UC) has a more severe presentation and rapid progression in pediatric patients, resulting in a greater need for surgical intervention compared to adults. Though medical management of UC has advanced with new biologic therapies, surgery continues to play an important role when disease progresses in the form of worsened or persistent symptoms, hemodynamic instability, or sepsis. The goals of surgical management are to restore intestinal continuity with a functional pouch when possible. While the literature has been growing regarding studies of pediatric patients with UC, high level of evidence studies are limited and most recommendations are based on adult studies. Similar to adults, pediatric patients who have ileal pouches created require surveillance for recurrent disease and cancer surveillance. Unique issues for pediatric patients include monitoring of growth and appropriate transition to adult care after adolescence. This review includes indications for surgical management, overview of staged surgical approaches, and the technical details of the three-stage approach. [ABSTRACT FROM AUTHOR]

Background/AimsTruelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin (an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indian population.MethodsConsecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized at a single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined.ResultsOut of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criterion, 33 (54%) had 2 additional criteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excluding hemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severe colitis.ConclusionsTruelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobin in the native population.

Background and Aim Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC. Methods This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point. Results Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk. Conclusions High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches. Methods: The literature was reviewed using the Medline/PubMed, Cochrane library and SciELO databases, and additional information from institutional websites of interest, by cross-correlating the following keywords: acute severe colitis, fulminating colitis and treatment. Results: Treatments for acute severe colitis have avoided colectomy in 60-70% of the cases, provided that they have been started early on, with multidisciplinary follow-up. Despite the adverse effects of intravenous cyclosporine, this drug has been indicated in cases of greater severity with an imminent risk of colectomy, because of its fast action, short half-life and absence of increased risk of surgical complications. Therapy using infliximab has been reserved for less severe cases and those in which immunosuppressants are being or have been used (AZA/6-MP). Indication of biological agents has recently been favored because of their ease of therapeutic use, their good short and medium-term results, the possibility of maintenance therapy and also their action as a "bridge" for immunosuppressant action (AZA/6-MP). Colectomy has been reserved for cases in which there is still no response five to seven days after rescue therapy and in cases of complications (toxic megacolon, profuse hemorrhage and perforation). Conclusion: Patients with a good response to rescue therapy who do not undergo emergency operations should be considered for maintenance therapy using azathioprine. A surgical procedure is indicated for selected cases.

Objectives: Acute severe colitis (ASC) occurs in up to 15 percent of children with ulcerative colitis, with a high index of morbidity and mortality. Treatment includes high-dose steroids, infliximab, and salvage therapies. Unfortunately, up to 20 percent of patients may need an urgent colectomy due to treatment failure. We report our experience using tofacitinib for the treatment of six patients., Methods: A retrospective review of our medical electronic records was conducted. We included every patient with ASC and treatment failure, in whom tofacitinib was used as a salvage therapy. Response, complications, and disease course were noted., Results: Six patients were included with Pediatric Ulcerative Colitis Activity Index (PUCAI) scores ranging from 65 to 85 on admission, and 35 to 85 before tofacitinib was started ( P 0.07). Median response time was 72 h. A median decrease of 40 points in PUCAI was noted ( P 0.00001). Mean length of stay was 18 days with discharge 9 days after tofacitinib introduction. Haemoglobin, albumin, fecal calprotectin, and CRP improved after tofacitinib ( P 0.02, P 0.02, P 0.025, and P 0.01, respectively). The mean follow-up was 8.5 months, four patients achieved complete remission and only one had a recrudescence of symptoms ( P 0.01). One patient had a systemic Epstein-Barr virus infection prior to tofacitinib therapy, which resolved with rituximab treatment. No other complications were noted., Conclusions: Tofacitinib response is rapid and impressive in children suffering from ASC, and the safety profile appears comparable to or better than other available treatments. In the future, tofacitinib should be integrated into pediatric protocols., Competing Interests: C. Deslandres served as an advisory board member and speaker for AbbVie, Jansen, and Organon. The rest of the authors have no conflict of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Background: Acute severe colitis (ASC) is conventionally diagnosed by Truelove and Witts' criteria which are non-specific and can be affected by other pathologic conditions. Fecal calprotectin (FCP) is a gut-specific marker of inflammation which can predict short-term outcomes in patients with ASC. We aimed to define the role of FCP in the diagnosis of ASC.Methods: This prospective observational cohort study included adult patients (> 18 years) with ulcerative colitis (UC) for whom FCP was measured and was under follow-up from April 2015 to December 2016. Patients were divided into two cohorts: (1) all consecutive hospitalized patients with ASC as defined by Truelove and Witts' criteria; (2) outpatients with active UC (defined by Mayo score) who did not fulfill Truelove and Witts' criteria. FCP levels were compared between the two cohorts, and a cutoff for FCP to diagnose ASC was determined.Results: Of 97 patients, 49 were diagnosed with ASC (mean age: 36.1 ± 11.9 years, 36 males) and 48 with active UC (mean age: 37.9 ± 12.4 years, 25 males). Median FCP levels were significantly higher in patients with ASC [1776(952-3123) vs 282(43-568) µg/g, p < 0.001] than mild to moderately active UC (n = 48) or moderately active UC [n = 35, 1776(952-3123) vs 332(106-700) µg/g, p < 0.001]. A FCP cutoff of 782 μg/g of stool had excellent diagnostic accuracy, with an area under the curve of 0.92(95% CI 0.87-0.97), sensitivity of 84% and specificity of 88% to differentiate ASC from active UC.Conclusion: FCP could differentiate ASC from mild to moderate patients with UC, but requires validation before clinical use. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Knowledge of long‐term outcomes following an index episode of acute severe colitis (ASC) can help informed decision making at a time of acute exacerbation especially when colectomy is an option. We aimed to identify long‐term outcomes and their predictors after a first episode of ASC in a large North Indian cohort. Methods: Hospitalized patients satisfying Truelove and Witts' criteria under follow‐up at a single center from January 2003 to December 2013 were included. Patients avoiding colectomy at index admission were categorized as complete (≤ 3 non bloody stool per day) or incomplete responders, based upon response to corticosteroids at day 7. Random Forest‐based machine learning models were constructed to predict the long‐term risk of colectomy or steroid dependence following an index episode of ASC. Results: Of 1731 patients with ulcerative colitis, 179 (10%) had an index episode of ASC. Nineteen (11%) patients underwent colectomy at index admission and 42 (26%) over a median follow‐up of 56 (1–159) months. Hazard ratio for colectomy for incomplete responder was 3.6 (1.7–7.5, P = 0.001) compared with complete responder. Modeling based on four variables, response at day 7 of hospitalization, steroid use during the first year of diagnosis, longer disease duration before ASC, and number of extra‐intestinal manifestations, was able to predict colectomy with an accuracy of 77%. Conclusions: Disease behavior of ASC in India is similar to the West, with a third undergoing colectomy at 10 years. Clinical features, especially response at day 7 hospitalization for index ASC, can predict both colectomy and steroid dependence with reasonable accuracy. [ABSTRACT FROM AUTHOR]

Background/Aims: Truelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin (an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indian population. Methods: Consecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized at a single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined. Results: Out of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criterion, 33 (54%) had 2 additional criteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excluding hemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severe colitis. Conclusions: Truelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobin in the native population. [ABSTRACT FROM AUTHOR]

Background and Aim: The extent of disease of ulcerative colitis (UC) has been found to be a predictor of acute severe colitis (ASC), but it is unclear whether the extent of disease at the index episode of ASC is a predictor of long‐term outcome. Methods: Hospitalized patients satisfying Truelove and Witts’ criteria under follow‐up at a single center from January 2003 to December 2016 were included. The extent of disease at index ASC was classified according to the Montreal classification as left‐sided or extensive colitis. Extent was used to predict the long‐term risk of colectomy or steroid dependence following an index episode of ASC. Results: Of 2076 patients with ulcerative colitis, 241 (12%) had an index episode of ASC. In total, 34 (14%) patients underwent a colectomy at index admission and 53 (26%) over a median follow‐up of 48(1–172) months. Left‐sided colitis and extensive colitis did not differ in the rate of colectomy at index admission (12% vs 15%, P = 0.4) and colectomy in follow‐up (31% vs 23%, P = 0.17). Readmission due to ASC was also similar between the two groups (28% vs 32%, P = 0.6). Conclusion: Extent of disease at index ASC does not predict colectomy at admission and over the long term. [ABSTRACT FROM AUTHOR]

Background and Aims: Early objective markers for failure of intravenous[iv] corticosteroid for acute severe colitis [ASC] can avoid delay in rescue therapy or colectomy. We investigated faecal calprotectin [FC], C-reactive protein [CRP], and endoscopy using the ulcerative colitis endoscopic index of severity [UCEIS] as predictors of steroid failure following intensive therapy of ASC. Methods: Consecutive patients with ASC satisfying Truelove and Witts' criteria, hospitalised at a single centre from May 2015 to November 2016, were included; all received iv corticosteroids. The primary outcome measure was steroid failure defined as colectomy and/or rescue therapy with ciclosporin or infliximab during admission. FC levels were measured at admission and on Day 3 of intensive therapy. UCEIS was scored at admission, and CRP on Day 3 of intensive therapy. Results: Of 49 patients, 21 [43%] failed iv corticosteroids and 15 [31%] underwent surgery. FC levels were significantly higher in steroid failures (2522 [590-9654] μg/g) compared with steroid responders (1530 [352-10 278] μg/g) at admission [p = 0.04], as well as on Day 3 of iv corticosteroid therapy (2718 [222-9175] μg/g vs 727 [218-4062] μg/g, p = 0.001). Steroid failures had a higher median [range] UCEIS score than responders (6 [4-8] vs 5 [4-7] [p = 0.001]). CRP level did not differ significantly between steroid failures and responders. A UCEIS > 6 at admission and FC > 1000 μg/g on Day 3 were independent predictors of steroid failure and need for rescue therapy/colectomy. Conclusions: All patients with UCEIS > 6 and Day 3 FC > 1000 μg/g failed iv corticosteroids. The UCEIS score on admission and Day 3 FC are early predictors of failure of ivcorticosteroid therapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute severe colitis [ASC] is associated with major morbidity. We aimed to develop and externally validate an index that predicted ASC within 3 years of diagnosis. Methods: The development cohort included patients aged 16-89 years, diagnosed with ulcerative colitis [UC] in Oxford and followed for 3 years. Primary outcome was hospitalization for ASC, excluding patients admitted within 1 month of diagnosis. Multivariable logistic regression examined the adjusted association of seven risk factors with ASC. Backwards elimination produced a parsimonious model that was simplified to create an easy-to-use index. External validation occurred in separate cohorts from Cambridge, UK, and Uppsala, Sweden. Results: The development cohort [Oxford] included 34/111 patients who developed ASC within a median 14 months [range 1-29]. The final model applied the sum of 1 point each for extensive disease, C-reactive protein [CRP] > 10 mg/l, or haemoglobin < 12 g/dl F or < 14 g/dl M at diagnosis, to give a score from 0/3 to 3/3. This predicted a 70% risk of developing ASC within 3 years [score 3/3]. Validation cohorts included different proportions with ASC [Cambridge = 25/96; Uppsala = 18/298]. Of those scoring 3/3 at diagnosis, 18/18 [Cambridge] and 12/13 [Uppsala] subsequently developed ASC. Discriminant ability [c-index, where 1.0 = perfect discrimination] was 0.81 [Oxford], 0.95 [Cambridge], 0.97 [Uppsala]. Internal validation using bootstrapping showed good calibration, with similar predicted risk across all cohorts. A nomogram predicted individual risk. Conclusions: An index applied at diagnosis reliably predicts the risk of ASC within 3 years in different populations. Patients with a score 3/3 at diagnosis may merit early immunomodulator therapy. [ABSTRACT FROM AUTHOR]

Background: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) accounts for 86% of the variance between observers in the overall assessment of endoscopic severity, but has not been correlated with outcomes. Methods: Consecutive cases of acute severe colitis (ASC) defined by Truelove and Witts (TW) criteria were retrospectively evaluated. Demographic details, number of TW criteria, prior medical therapy, UCEIS and inpatient medical therapy were recorded. Pre-specified (adverse) endpoints included rescue therapy, colectomy and readmission. Results: Eighty-nine patients, 48 (54%) male, mean age 38 years, all received intravenous hydrocortisone 400 mg/d (median 5 days [range 1-11]). Median follow-up was 14 months (2-33). Forty-eight (54%) were diagnosed the year prior to or at the time of admission. Thirty-six (40%) required rescue therapy (infliximab 25/36, ciclosporin 12/36, one receiving both). Twenty-one (24%) underwent colectomy on the index admission (9/21) or during follow-up (12/21). Median UCEIS score (possible range 0-8) was 5 (3-8). UCEIS was higher in patients requiring rescue therapy or colectomy (median score 6 [range 4-8] versus 5/8 [3-8], both p < 0.005). For UCEIS ≥5, 27/54 (50%) required rescue therapy, compared with 9/33 (27%) for UCEIS ≤4 (p = 0.037). When UCEIS was ≥5, 18/54 (33%) came to colectomy during follow-up, compared with 3/33 (9%) with UCEIS ≤4. Of 14 patients with UCEIS 7 or 8, 11/14 needed rescue therapy and 13/14 met any adverse endpoint. Conclusion: Endoscopic severity is associated with a worse outcome in ASC. When the UCEIS is ≥7 on admission, almost all patients will need treatment with infliximab or ciclosporin beyond steroids. This may mark a threshold for an early decision to use infliximab or ciclosporin. [ABSTRACT FROM AUTHOR]

Response to corticosteroid treatment in acute severe ulcerative colitis (ASUC) has changed very little in the past 50 years. Predicting those at risk at an early stage helps stratify patients into those who may require second line therapy or early surgical treatment. Traditionally, risk scores have used a combination of clinical, radiological and biochemical parameters; established indices include the 'Travis' and 'Ho' scores. Recently, inflammatory bowel disease genetic risk alleles have been built into models to predict outcome in ASUC. Given the multifactorial nature of inflammatory bowel disease pathogenesis, in the future, composite scores integrating clinical, biochemical, serological, genetic and other '-omic' data will be increasingly investigated. Although these new genetic prediction models are promising, they have yet to supplant traditional scores, which remain the best practice. In this modern era of rescue therapies in ASUC, robust scoring systems to predict failure of ciclosporine and infliximab must be devised. [ABSTRACT FROM AUTHOR]

Toxic megacolon is a rare and serious complication of Crohn’s disease. Because of the associated high morbidity and mortality, early recognition and management of toxic megacolon is important. Through two cases of toxic megacolon complicating Crohn’s disease, we assessed the clinical, radiologic and therapeutic characteristics of this complication. A 35-year-old man presented a first course of Crohn’s disease treated with corticosteroid. He exhibited sudden severe abdominal pain and distension with shock. A plain abdominal radiography revealed toxic megacolon. He underwent medical therapy, but symptoms not relieved. The patient underwent subtotal colectomy with ileostomy. The resected specimen confirmed the diagnosis. Recovery of digestive continuity was performed. Endoscopic evaluation six months later did not shown recurrence. A 57-year-old man presented with severe acute colitis inaugurating Crohn’s disease, was treated with corticosteroid and antibiotics. He exhibited signs of general peritonitis. Computed tomographic examination revealed toxic megacolon with free perforation, showing prominent dilation of the transverse colon and linear pneumatosis. The patient underwent emergent subtotal colectomy and ileostomy. The final histological patterns were consisting with diagnosis of Crohn’s disease associated with cytomegalovirus infection. The patient underwent antiviral therapy during 15 days. Because of the high risk of postoperative recurrence, he underwent immunosuppressive therapy. Recovery of digestive continuity was performed successfully. Toxic megacolon in Crohn’s disease is a serious turning of this disease. We underscore the importance of early diagnosis of toxic megacolon and rapid surgical intervention if improvement is not observed on medical therapy.

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Copyright of Colon & Rectum is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute severe colitis (ASC) may occur within 3 months of ulcerative colitis diagnosis in 9%-15% of children and the rate of colectomy is up to 40%-50% within 5 years after an ASC. The aim of this publication is to present recent and relevant data on the success of medical treatment with tofacitinib in ASC., Methods: We report a challenging case of a teenage boy with ASC at diagnosis and conduct a discussion after a review of the literature regarding the use of tofacitinib in inflammatory bowel disease, especially in pediatric patients and in ASC., Results: The patient was hospitalized for 10 weeks and was refractory to conventional therapies: intravenous corticosteroids, infliximab, methotrexate, and vedolizumab. He received 7 blood transfusions and also presented with a severe malnutrition requiring a total parenteral nutrition. Tofacitinib was considered as a medical last resort before colectomy and was started at week 8. Thirteen days after starting tofacitinib, he was asymptomatic and was discharged on tofacitinib as sole treatment. By week 9 of tofacitinib, a colonoscopy showed both endoscopic and histological remission. He has remained in clinical remission at 6-month follow-up., Conclusions: Tofacitinib may be an alternative medical treatment to avoid colectomy in ASC. It is a small molecule with a rapid onset and few severe adverse events. It has been used for ASC in adult patients, allowing to avoid colectomy in more than 60%. To our knowledge, this is one of the few pediatric patients with refractory ASC at initial diagnosis who responded to tofacitinib., Competing Interests: Dr Deslandres served as advisory board member and speaker for AbbVie and Janssen. The remaining authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Abstract: Background: The prognosis of acute severe ulcerative colitis (ASC) influences therapeutic decisions, but data on prevalence or long-term outcome are few. Methods: A systematic review of all patients with UC diagnosed in Oxford was performed to assess the prevalence of ASC defined by Truelove and Witts'' (TW) criteria and determine whether outcome is related to disease activity on admission, likelihood of recurrence and long-term prognosis. Results: 750 patients (median follow up 12.7yr, range 0–648mo) met inclusion criteria out of a total cohort of 1853 patients. 24.8% (186/750) had at least one admission for ASC (294 admissions in 186 patients). Overall, 12% (93/750) had a colectomy, compared to 39.8% (74/186) of patients with one or more episodes of ASC (p <0.0001) and 3.4% (19/564) in those with no admission. The colectomy rate on first admission (37/186, 19.9%) was lower than on the second or subsequent admissions (OR 2.35, 95% CI 1.33–4.14, p =0.003), being 29.0%, 36.6%, 38.2% after two, three, or subsequent episodes respectively. It was 8.5% (11/129) if patients had one TW criterion in addition to ≥6 bloody bowel motions/day, compared to 31% (29/94) if two additional criteria were present and 48% (34/71) if three or more additional criteria were present (p =1.4×10−5; OR 4.35, 95% CI 2.20–8.56 one criterion vs two or more). Conclusions: A quarter of all patients with ulcerative colitis experience at least one episode of ASC; 20% come to colectomy on first admission, but 40% after two admissions. The likelihood of colectomy is related to biological severity on admission. [Copyright &y& Elsevier]