Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.

Approximately one in every four patients with ulcerative colitis will develop acute severe ulcerative colitis (ASUC). Historically, this was managed with intravenous steroids and surgery when steroids failed. The use of rescue therapy.

This review summarizes the latest research in the management of hospitalized patients with ASUC. Covering the historical data and success of rescue therapy with cyclosporine and then with infliximab changed outcomes and reduced the risk of colectomy during the hospitalization and at 1 year. More recently, more biologics and small molecules have been approved and more patients present to the hospital with ASUC already failing anti-tumor necrosis factor antagonists. More recent studies have shown some efficacy of rescue therapy with other classes of biologics (e.g. interleukins and anti-integrins). The more recently approved small molecules (i.e. tofacitinib and Upadacitinib) have shown a rapid onset in therapeutic efficacy in as little as 1 day with sustained response at 1 year in reducing the risk of colectomy following ASUC.

In the expert opinion, we discuss the challenges in the treatment of patients with ASUC. We summarize the data of current biologics and new small molecules and their emerging roles in the management of ASUC.

Ulcerative colitis (UC) is an inflammatory bowel disease in which one-quarter of patients are at risk of developing a severe form of the disease known as acute severe UC (ASUC). This condition exposes patients to serious complications, including toxic megacolon, surgical intervention, and even death. The current therapeutic strategy relies on time-dependent, multi-step algorithms that integrate systemic corticosteroids, calcineurin inhibitors, and biologic agents (specifically infliximab) as medical therapy aimed at avoiding colectomy. Despite this approach, a significant proportion of patients fail to respond to either corticosteroids or infliximab and may require alternative therapeutic options if there is no urgent surgical necessity. These alternatives include other biologics or emerging small molecules, although the evidence supporting these treatments remains extremely low, even considering their well-documented and promising efficacy and safety in moderate-to-severe UC. Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators.

Endoscopy and biopsy are the standard tools for the diagnosis of inflammatory bowel disease (IBD) and the assessment of treatment response. Severe endoscopic lesions (SEL) are commonly observed in IBD, but have been poorly described in the literature. The aim of this review is to provide an overview of the current understanding and gaps in knowledge about these lesions.

We performed a systematic review of studies of SEL in patients with IBD. A search was performed in MEDLINE, Embase, and Cochrane CENTRAL databases in July 2024. Studies were eligible if they investigated SEL, its involvement in the disease, its evolution with treatment, and its prognostic implications.

We found 1172 articles in the Pubmed database and 46 were included. Of the various definitions of SEL used in the literature, most of them are based on the most severe endoscopic items from existing endoscopic scores, but none have been validated. Despite the paucity of literature, the prevalence of SEL is estimated to be 33%-75% in acute severe ulcerative colitis (ASUC) and 22.5%-87% in Crohn's disease (CD). In terms of prognosis, SEL are associated with steroid refractoriness in ASUC and do not affect response to infliximab or ciclosporin. In CD, the response to biologics, especially anti-TNF, is not affected by the presence of SEL.

There is currently no validated definition of SEL in IBD. When present, they are associated with steroid failure in the setting of ASUC, but do not affect response to anti-TNF in either CD or ASUC.

One-third of patients with acute severe ulcerative colitis (ASUC) are steroid-refractory. Cyclosporine and infliximab are currently the mainstays of salvage therapy. Janus kinase inhibitors (JAKi) could play a role in the treatment of ASUC.

To review the evidence on JAKi in the management of ASUC.

We performed a bibliographic search to identify studies focusing on the treatment of ASUC with JAKi.

Potential advantages of JAKi for the management of ASUC include their oral administration, rapid onset of action, short half-life, lack of immunogenicity, and effectiveness in patients with prior biologic exposure. Thirty studies (including 373 patients) have evaluated the efficacy of tofacitinib in ASUC, with a response rate (avoidance of colectomy) ranging between 43% and 100%, with a weighted mean of 82%. Experience with upadacitinib is more limited (only 10 studies and 74 patients are available) but also encouraging: mean colectomy-free rate ranging between 67% and 100%, with a weighted mean of 79%. However, experience with filgotinib in ASUC is currently nonexistent. Regarding safety, the available data does not reveal any new safety concerns when JAKi are used in ASUC, although follow-up periods are still short.

JAKi seems to be a promising treatment option for ASUC, with both tofacitinib and upadacitinib achieving colectomy-free rates of approximately 80%. Further studies are essential to define whether JAKi can replace cyclosporine/infliximab as second-line therapy for the medical management of ASUC, or whether they can even be used as initial treatment in place of intravenous corticosteroids.

Small molecule Janus kinase (JAK) inhibitors have revolutionized the management of ulcerative colitis (UC) and Crohn's disease (CD) through their low immunogenicity, safety, and consistent pharmacologic response that are superior to existing therapeutic options. In this perspective, we highlight existing evidence supporting the use of currently approved JAK inhibitors (upadacitinib, tofacitinib, and filgotinib) for UC or CD, additionally emphasizing the evidence for their use in related autoimmune conditions such as rheumatoid arthritis and spondyloarthropathies. Our perspective concludes with a review of the existing comparative effectiveness literature, which positions JAK inhibitors, particularly upadacitinib, favorably compared with other biologic therapies. This perspective is paired with a companion publication highlighting the origins and development of JAK inhibitors and a more in-depth review of their pathophysiologic mechanisms.

It is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids.

We conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids. Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX+AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm). The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse event leading to treatment interruption, colectomy or death. Multiple imputation for missing data was performed.

Among the 64 patients randomised (Lichtiger score 13.5±2.0; median age of 34.5 (P25-P75 26.3-50.3) years, median C reactive protein of 29.0 (12.8-96.8) mg/L at baseline): 32 were assigned to the IFX+AZA arm and 32 to the AZA arm. In the ITT population, treatment failure at week 52 was observed in 22/27 (81.5%) in the AZA arm and 16/30 (53.3%) in the IFX+AZA arm (risk ratio 3.85, 95% CI (1.15 to 12.88), p=0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms.

Combination therapy with IFX+AZA was more effective at 1 year than AZA alone to avoid treatment failure in patients with ASUC responding to intravenous steroids.

NCT02425852.

There is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.

Available guidelines lack in indications on surgical standard in Ulcerative Colitis (UC) AIMS: To determine the role of surgical strategies of colectomy and proctectomy with pouch-anal-anastomosis (IPAA) on functional outcomes in a nationwide population multicenter study. The secondary aims consisted of perioperative outcomes and complications.

Data on 379 patients who underwent total abdominal colectomy and proctectomy with ileo-pouch-anal-anastomosis (IPAA) with or without diverting ileostomy were retrospectively collected in a red cap multicenter-database searching for variables that could impact on pouch outcomes as cuffitis, pouchitis, anastomotic stenosis, pouch stenosis, failure or pathological Low-Anterior-Resection-Syndrome (LARS) score.

Mesocolic dissection sealing vessels at major trunks and from medial to lateral are associated with better outcomes. Laparoscopy is associated with lower rate of cuffitis over time (p = 0.028). Mesentery lengthening is associated with higher pouchitis rate (p = 0.015) and earlier failure (p < 0.0001). Hand-sewn IPAA results in early anastomotic stenosis (p = 0.00011). The Transanal-Transection and Single-Stapling Anastomosis (TTSS) showed to be protective against pouchitis. Extended dissection of adhesions correlates with lower rate of pouchitis-episodes (p = 0.0057).

The study highlights advantages of laparoscopy. New techniques such as TTSS promise further improvements. Mesentery lengthening correlates with high risk of pouch-failure and pouchitis, hand-sewn anastomosis increased risk of stenosis.

Acute severe ulcerative colitis (ASUC) is a critical manifestation of ulcerative colitis (UC), often necessitating colectomy when medical management fails. Despite advancements in therapeutic interventions such as corticosteroids, biologics, and JAK inhibitors, a significant proportion of patients require surgery, with colectomy rates ranging from 10% to 15%.

This paper reviews the factors influencing the timing and necessity of colectomy in ASUC management, emphasizing the importance of multidisciplinary decision-making involving gastroenterologists and surgeons.

Key surgical indications include failure of medical therapy, toxic megacolon, perforation, uncontrolled bleeding, and systemic deterioration. Delays in surgery can result in higher morbidity and mortality rates, making timely intervention essential. This review highlights surgical techniques, including total colectomy and end ileostomy, and discusses potential complications, urging a balanced approach to optimize patient outcomes.

While corticosteroids have led to significant reduction in ASUC mortality over the last few decades, they are associated with significant side effects and up to 30% of patients have steroid refractory ASUC, which means we require safer and better therapies for patients with ASUC. Several salvage therapies have been proposed in guidelines; however, we lack high quality head-to-head randomised controlled trials to assess effectiveness and safety of these agents. Furthermore, the role of newer novel agents in ASUC management is unclear. We aim to present an up to date review and envisage future treatment of ASUC without steroids based on current trials and data. In summary, we conclude that ASUC treatment still heavily relies on corticosteroids despite the side effect profile. While infliximab and cyclosporine have extensive data, there are no prospective studies comparing them with corticosteroids as initial therapy. Novel therapies open up the possibility of oral options but require prospective data before any conclusion can be made.

Mucosal deficiency is one of the most challenging conditions in patients with acute severe ulcerative colitis (ASUC). Intravenous corticosteroids (CS) are the first-line treatment, with infliximab (IFX) used as a rescue therapy. However, the efficacy remains unsatisfactory. We investigated whether CS combined with IFX as first-line therapy would improve outcomes in patients with ASUC with mucosal deficiency.

A retrospective study was performed at a tertiary inflammatory bowel disease center. The primary outcomes included clinical remission, endoscopic improvement, and endoscopic remission at week 14. The secondary outcomes included the colectomy rate within 90 days and durable clinical remission.

A total of 43 patients with ASUC with mucosal deficiency were included in the analysis (25 in the CS combined with the IFX group and 18 in the CS sequential IFX group). At week 14, endoscopic improvement was observed in 21 of 25 patients (84.0%) receiving the CS combined with the IFX regimen, compared to 9 of 18 (50.0%) patients receiving the CS sequential IFX regimen (p = 0.017). Durable clinical remission rates were significantly higher in the combined group than in the sequential group (85.7% vs. 35.7%, p = 0.004). There was no statistically significant difference between the two groups in terms of clinical and endoscopic remission at week 14 or colectomy rate within 90 days. Multivariate analysis confirmed that the CS combined with the IFX regimen was an independent predictive factor for a higher endoscopic improvement rate at week 14 (odds ratio (OR) 8.428, 95%confidence interval (CI) 1.539-46.153, p = 0.014) and a higher durable clinical remission rate (OR 10.800, 95%CI 2.095-55.666, p = 0.004).

CS combined with IFX as first-line therapy may be an effective induction strategy in patients with ASUC with mucosal deficiency. Further large-scale, multicenter prospective studies are needed.

The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC.

In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed.

Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study.

Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3.

Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis (UC) that can lead to significant morbidity and mortality, with a substantial number of patients needing colectomy. Infliximab (IFX) has been increasingly used as a rescue therapy for patients who have failed intravenous steroids and has been more frequently used as an induction and maintenance therapy in moderate-to-severe UC. Therefore, the number of patients admitted with ASUC previously exposed to IFX has been increasing, raising additional challenges in the medical management of these patients to avoid emergent colectomy. This narrative review intends to summarise the most recent evidence in the medical management of steroid-refractory ASUC patients previously exposed to IFX and to propose a treatment algorithm for approaching this difficult-to-treat group of patients.

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.

Acute severe ulcerative colitis (ASUC) is a medical emergency that affects approximately 25% of patients with ulcerative colitis at some point in time in their lives. Outcomes of ASUC are highly variable. Approximately 30% of patients do not respond to corticosteroids and up to 50% of patients do not respond to rescue therapy (infliximab or cyclosporin) and require emergency colectomy. Data are emerging on infliximab dosing strategies, use of cyclosporin as a bridge to slower acting biologic agents and Janus kinase inhibition as primary and sequential therapy. In this review, we outline contemporary approaches to clinical management of ASUC in the setting of failure to respond to traditional rescue therapies.

Upadacitinib is an oral new selective JAK1 inhibitor that has been approved for treating adult patients with moderately to severely active ulcerative colitis. However, a growing number of studies are needed on the effectiveness of upadacitinib in the treatment of acute severe ulcerative colitis. This study was mainly aimed to describe the clinical and endoscopic effectiveness of upadacitinib 45 mg in Chinese acute severe ulcerative colitis patients following eight weeks of treatment. In this study, we examined all patients with acute severe ulcerative colitis from Xijing IBD Center, Xi'an, China, with acute severe ulcerative colitis. All patients were initially given oral upadacitinib 45 mg. Clinical indicators, C-reactive protein, and erythrocyte sedimentation rates were collected. Clinical response and clinical remission were assessed using modified Mayo. Endoscopic evaluation was performed carried out using the Mayo Endoscopic Score and Ulcerative colitis endoscopic index of severity score. A total of 14 patients who received upadacitinib were included in the study period. All patients exhibited a clinical response to 45 mg upadacitinib initially. All patients completed the 8-week induction. The clinical remission rate was 28.6% after eight weeks. Two patients revealed endoscopic remission at 14.3%. The pathology improved in 50.0% of patients. The 8-week surgical resection rate was 7.1%, with the 16-week surgical resection rate being 14.3%. Adverse events included herpes simplex virus infection and increased thrombin time. The results of our study support the short-term effectiveness and safety of upadacitinib in acute severe ulcerative colitis, providing new choices for patients' treatment. However, more extended investigation needs to be performed on the long-term effectiveness and safety.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening medical emergency that occurs in up to 25% of patients with ulcerative colitis. Although intravenous corticosteroids remain the cornerstone of therapy, 30-40% of patients will not respond and need timely consideration of rescue therapy with (currently) either infliximab or ciclosporin or indeed colectomy, underscoring the importance of multidisciplinary care to ensure favourable outcomes for patients. We discuss the current evidence and present an approach to the management of ASUC for general and specialist clinicians caring for patients with ASUC.

The information in this review is derived from data published in peer- reviewed academic journals and registered clinical trials.

Management of acute severe colitis requires a multidisciplinary approach with early initiation with steroids and timely escalation of treatment to either medical rescue therapy or surgery.

Balancing the risks of delayed surgery vs. optimizing medical therapy, including accelerated dosing schedules for biologics, remains ambiguous.

The position on newer molecules like Janus Kinase inhibitors, such as tofacitinib, is a growing area with early real-world data showing promise for steroid refractory ASUC.

Developing predictive biomarkers and clinical risk scores for personalized rescue therapy selection is an evolving area of research.

Recent advancements in the treatment landscape of ulcerative colitis (UC) have ushered in a new era of possibilities, particularly with the introduction of Janus kinase (JAK)-signal transducer and activator of transcription inhibitors. These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes. With approved JAK inhibitors (JAKis), such as tofacitinib, filgotinib, and upadacitinib, clinicians now have powerful tools to modulate immune responses and gene expression, potentially revolutionizing the treatment algorithm for UC. Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission, presenting viable options for patients who have failed conventional therapies. Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy, particularly in patients with aggressive disease phenotypes or refractory to biologic agents. The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC, offering timely relief for patients with active disease and facilitating personalized treatment approaches. Despite safety concerns, including cardiovascular risks and infections, ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.

Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients.

In steroid-refractory acute, severe, ulcerative colitis (ASUC), salvage medical therapy with infliximab is recommended to reduce the risk of colectomy. However, the evidence supporting this practice is based on cohorts naïve to biologics. Consequently, the management of patients on biologic or small molecule therapy (BST) with ASUC is not well defined.

We conducted a retrospective chart review of patients admitted with ASUC to Mount Sinai Hospital (MSH) in Toronto, Ontario from January 2018 until January 2022. Included subjects were considered to be on BST if they had received a dose of these agents within 56 days prior to admission. Our outcomes of interest included the mean difference in hospital length of stay (HLOS), rates of surgical consultation, rates of inpatient colectomies, and 90-day readmission rates between the 2 groups.

Of the 185 admissions for ASUC, 76 were on BST prior to admission and 109 were not. Baseline characteristics were similar between the 2 groups. There were no significant differences in hospital length of stay (7.46 days vs 7.45 days P = .52) or in-hospital colectomy rates between the 2 groups. Patients on BST had higher rates of surgical consultation (36.8% vs 8.3% P < .01) and 90-day readmission rates (26.3% vs 13.8% P = .03).

We did not identify significant differences in the majority of our outcomes between the 2 groups. However, patients on BST were more likely to receive a surgical consultation during their admission and had higher rates of readmission at 90 days. Further studies evaluating the underlying factors that contribute to readmission in patients on BST in hospitals are needed.

Acute Severe Ulcerative Colitis (ASUC) is a severe form of ulcerative colitis relapse which requires hospitalization and intensive medical intervention to avoid colectomy. The timely recognition of patients at risk of corticosteroid failure and the early initiation of medical rescue therapy are paramount in the management of ASUC. The choice of medical rescue therapy is influenced by multiple factors, especially patient's prior treatment history. This decision should involve the patient and ideally a multidisciplinary team of healthcare professionals, including gastroenterologists, radiologists, surgeons and enterostomal therapists. Although several predictive models have been developed to predict corticosteroid failure in ASUC, there is no single validated tool that is universally utilized. At present, infliximab and cyclosporine are the only agents systematically evaluated and recommended for medical rescue therapy, with recent reports of off-label utilization of tofacitinib and upadacitinib in small case series. The available evidence regarding the efficacy and safety of these oral small molecules for ASUC is insufficient to provide definitive recommendations. Early decision-making to assess the response to medical rescue therapy is essential, and the decision to pursue surgery in the case of treatment failure should not be delayed.

Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis.

We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis.

This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group ( P  < 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUC > 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%).

IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity. Despite recent advances in medical IBD therapy, colectomy rates for ASUC remain high. A scoping review of published articles on ASUC was performed. We collected data, such as general information of the disease, diagnosis and initial assessment, and available medical and surgical treatments focusing on technical aspects of surgical approaches. The most relevant articles were considered in this scoping review. The management of ASUC is challenging; currently, personalized treatment for it is unavailable. Sequential medical therapy should be administrated, preferably in high-volume IBD centers with close patient monitoring and indication for surgery in those cases with persistent symptoms despite medical treatment, complications, and clinical worsening. A total colectomy with end ileostomy is typically performed in the acute setting. Managing rectal stump is challenging, and all individual and technical aspects should be considered. Conversely, when performing elective colectomy for ASUC, a staged surgical procedure is usually preferred, thus optimizing the patients' status preoperatively and minimizing postoperative complications. The minimally invasive approach should be selected whenever technically feasible. Robotic versus laparoscopic ileal pouch-anal anastomosis (IPAA) has shown similar outcomes in terms of safety and postoperative morbidity. The transanal approach to ileal pouch-anal anastomosis (Ta-IPAA) is a recent technique for creating an ileal pouch-anal anastomosis via a transanal route. Early experiences suggest comparable short- and medium-term functional results of the transanal technique to those of traditional approaches. However, there is a need for additional comparative outcomes data and a better understanding of the ideal training and implementation pathways for this procedure. This manuscript predominantly explores the surgical treatment of ASUC. Additionally, it provides an overview of currently available medical treatment options that the surgeon should reasonably consider in a multidisciplinary setting.

The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy.

To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin.

Multicentre retrospective cohort study of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment.

Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy.

Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients.

Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented.

A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively.

Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

Acute severe ulcerative colitis (ASUC) is a distinctive ulcerative colitis flare presentation characterised by the presence of systemic inflammation as well as bloody diarrhoea, and occurs at least once in 25% of patients with ulcerative colitis during their disease course. Each episode carries a risk of complications, need for colectomy, and mortality. Little is known about ASUC pathogenesis, although impaired host-microbiota crosstalk involving pathobionts is suspected. In this Review, we discuss unanswered questions and results from the latest research on the medical-first-line, second-line, and potential third-line therapies-and surgical management of ASUC. We detail promising options for management, such as the use of enteral nutrition in combination with intravenous steroids, the ability to predict early failure of first-line or second-line therapies, and the emerging role of JAK inhibitors. An optimal framework to personalise therapy on the basis of multiomics tools is yet to be developed.

Acute severe ulcerative colitis (ASUC) is one of life-threatening complications that occur in one-fifth of ulcerative colitis (UC) patients with significant morbidity and an estimated mortality rate up to 1%. There are no validated clinical scoring systems for ASUC. Intravenous corticosteroids remain the cornerstone for the management of ASUC patients However, one-third of patients are steroid refractory and require colectomy in the pre-biologic era or salvage therapy in the post-biologic era. The currently available predictors of non-response to steroids and salvages therapy are sub-optimal. Furthermore, there is a need for the development of clear outcome measures for ASUC patients. Although infliximab and cyclosporin are both effective as salvage therapy, they still carry a rate of treatment failure. Hence, there is an unmet need to explore alternative therapeutic options before colectomy particularly in prior infliximab-exposed patients. This may include the introduction of small molecules with rapid onset of action as a salvage or sequential therapy and the use of slow-onset other biological therapy after "bridging" with cyclosporine. In this article, we explore the current best evidence-based practice and detail the gaps in knowledge in the management of ASUC.

Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. The precise mechanism by which JAK-STAT inhibitors may impact the pathogenetic process of ICI colitis remains inadequately understood. However, there is speculation regarding their potential role in modulating memory resident CD8+ T lymphocytes. The elucidation of this mechanism requires further extensive and robust evidence, and ongoing JAK-STAT-based trials are anticipated to contribute valuable insights.

Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab.

Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes.

All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified.

Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.

The management of hospitalized patients with inflammatory bowel disease (IBD) is complex. Despite considerable therapeutic advancements in outpatient ulcerative colitis and Crohn's disease management, the in-hospital management continues to lag with suboptimal outcomes. The purpose of this review is to provide a brief overview of our approach to managing patients hospitalized with acute severe ulcerative colitis (ASUC) and Crohn's disease-related complications, followed by a summary of emerging evidence for new management approaches.

ASUC has seen the emergence of well validated prognostic models for colectomy as well as the development of novel treatment strategies such as accelerated infliximab dosing, Janus kinase inhibitor therapy, and sequential therapy, yet the rate of colectomy for steroid-refractory ASUC has not meaningfully improved. Crohn's disease has seen the development of better diagnostic tools, early Crohn's disease-related complication stratification and identification, as well as better surgical techniques, yet the rates of hospitalization and development of Crohn's disease-related complications remain high.

Significant progress has been made in the in-hospital IBD management; however, both the management of ASUC and hospitalized Crohn's disease remain a challenge with suboptimal outcomes. Critical knowledge gaps still exist, and dedicated studies in hospitalized patients with IBD are needed to address them.