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.

Zinc is an essential element and important for inflammatory bowel disease patients. Herein, we aimed to elucidate the correlation between serum zinc concentration and various parameters, especially the disease activity index and endoscopic scores, in these patients. We measured serum zinc concentrations in 37 patients with Crohn's disease and 64 with ulcerative colitis and retrospectively analyzed patient characteristics, blood test values, disease activity, and endoscopic scores. Hypozincemia (<80 ‍μg/dl) was observed in 45.9% and 29.7% of patients with Crohn's disease and ulcerative colitis, respectively. Serum zinc concentration showed a weak negative correlation with Crohn's Disease Activity Index and C-reactive protein levels in Crohn's disease patients, and a weak negative correlation with white blood cell count in ulcerative colitis patients. The zinc concentrations in ulcerative colitis patients were significantly lower in Mayo endoscopic sub-score grade 2 than in grades 0 and 1. The simple endoscopic score for Crohn's disease moderately correlated with zinc concentration. In addition, serum zinc concentration showed a moderate correlation with serum albumin and Onodera's prognostic nutritional index in both Crohn's disease and ulcerative colitis patients. Serum zinc concentration clearly correlated with inflammatory bowel disease activity, endoscopy scores, and immunonutritional parameters, suggesting the importance of monitoring zinc levels.

Interventional clinical trials in acute severe ulcerative colitis (ASUC) are characterized by substantial heterogeneity due to a lack of consensus in several key areas of trial design-this impedes clinical research efforts to identify novel therapies. The objective of this initiative was to achieve the first consensus and provide clear position statements on ASUC trial design.

A modified Delphi consensus approach was employed with a panel of 20 clinicians with international representation and expertise in ASUC trial design and delivery. Agreement was defined as at least 75% of participants voting as "agree" with each statement.

In total, 30 statements achieved consensus and were approved. Statements centred on proposing suitable eligibility criteria (disease extent, disease severity, prior therapy exposure), optimizing trial design (randomization, stratification, corticosteroid handling, timing of assessments), and recommending primary and secondary endpoints alongside defining key efficacy outcomes (clinical and endoscopic response and remission, treatment failure, quality of life).

The expansion of drugs to treat moderate-severe ulcerative colitis over the past decade, particularly the rapidly acting Janus kinase inhibitors, is promising and has reignited the interest in identifying suitable therapeutic candidates for ASUC. Clinical trials in this high-risk population are challenging to conduct and this consensus provides a framework for future trials to advance drug development.

Acute severe ulcerative colitis (ASUC), characterised by bloody diarrhoea and systemic inflammation, is associated with a significant risk of colectomy and a small risk of mortality. The landmark trial of cortisone in 1955 was pivotal for two reasons: first, for establishing the efficacy of a drug that remains a first-line therapy today and, second, for producing the first set of disease severity criteria and clinical trial endpoints that shaped the subsequent ASUC trial landscape. Trials in the 1990s and at the turn of the millennium established the efficacy of infliximab and ciclosporin, but since then, there has been little progress in drug development for this high-risk population. This systematic review evaluates all interventional randomised controlled trials (RCTs) conducted in patients hospitalised with severe UC. It provides an overview of the efficacy of treatments from past to present and assesses the evolution of trial characteristics with respect to study populations, eligibility criteria and study designs over time. This review details ongoing RCTs in this field and provides a perspective on the challenges for future clinical trial programmes and how these can be overcome to help deliver novel ASUC therapies.

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.

Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC.

This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population.

A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis.

In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

The patient was a 50-year-old Japanese woman who was diagnosed with total-colitis-type ulcerative colitis (UC) at the age of 26 years. She was treated with mesalazine and azathioprine, and her disease activity was well controlled. At the age of 50 years, the patient was experiencing fever, abdominal pain, diarrhea, bloody stool, and anal pain, which led to a diagnosis of a relapse of UC. Although steroid therapy was administered and tended to improve her symptoms, fecaloid vaginal discharge occurred, and rectovaginal fistula (RVF) was confirmed. Colostomy was performed, and infliximab was initiated as maintenance therapy for UC. All symptoms improved, and RVF closure was confirmed 6 months after the initiation of infliximab. To date, she has been free from relapse of UC. There have been only a few reports of UC complicated by RVF, and this condition is often difficult to treat. To the best of our knowledge, no other case of UC complicated by RVF in which the fistula was closed after treatment with colostomy and infliximab has been previously reported; thus, our report of the present case is valuable to the literature.

Predicting the efficacy of molecular-targeted drugs (MTDs) is an unmet need in the treatment of ulcerative colitis (UC). Intestinal ultrasound (IUS) can be used to safely and repeatedly assess UC activity.

Thirty-eight patients who started MTD therapy for active UC and underwent IUS at baseline and 3 months after starting therapy were analyzed. Steroid-free clinical remission (SFCR) and endoscopic improvement (EI) at 6 months were defined as a Lichtiger index of ≤3 and Mayo endoscopic subscore of ≤1 while continuing the MTD without steroid induction or surgery. Sonographically estimated EI (SE-EI) at 3 months was assessed based on a Milan Ultrasound Criterion of ≤6.2 and Kyorin Ultrasound Criterion for UC (bowel wall thickness of <3.8 mm and submucosa index of <50%).

Thirty-one patients achieved SFCR at 6 months [SFCR(+) group]. The SFCR(+) group demonstrated significantly better improvement in bowel wall thickness and bowel wall vascularity at 3 months than the SFCR(-) group. The Milan Ultrasound Criterion and UC-IUS index also improved significantly more in the SFCR(+) than SFCR(-) group. The areas under the curve of these parameters for predicting SFCR were approximately 0.80. Colonoscopy was performed for 28 patients at 6 months, and 15 patients achieved EI. SE-EI at 3 months was significantly associated with achievement of EI at 6 months. The positive predictive values of SE-EI at 3 months for SFCR and EI at 6 months were 100%.

Sonographic improvements in 3 months predicted the clinical and endoscopic efficacy of MTD therapy at 6 months, suggesting the longitudinal significance of IUS monitoring for UC treatment.

Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC.

We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA + AZA group. We compared the remission maintenance rates in the AZA and ADA + AZA groups for up to 5 years after TAC discontinuation.

In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA + AZA group (n = 16) exhibited a significantly higher relapse-free rate than the AZA group (n = 26) (p < 0.05; log-rank test).

switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

Inflammatory bowel diseases including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by abdominal pain, diarrhea, blood in stools, weight loss, and fatigue. It presents in patients with varying severity from mild to severe depending on the inflammation. Detailed analysis and guidelines are required for the safe usage of biological therapies in the treatment of inflammatory bowel diseases as surgery is reserved for more complex cases. There is also geographical variation in inflammatory bowel disease (IBD) incidence and prevalence based on environmental and climate changes, and socio-demographics. Studies also show that there is more hospitalization and reduced health-related quality of life in IBD patients when compared to normal people. We conducted an extensive literature database search for articles with keywords within the last 10 years on adults >18 years of age with IBD and its treatment, especially with ustekinumab. Ustekinumab is a human immunoglobulin G1 (IgG1) kappa monoclonal antibody, that blocks IL-12 and IL-23 and was approved by the FDA for the treatment of moderate to severe IBD, especially in patients who are intolerant to immunomodulators or corticosteroids treatment. There are several retrospective studies that show the effectiveness of ustekinumab dosage escalation every four weeks in IBD patients. This escalation of dose not only improved the clinical outcome but also reduced the worsening of the disease. Previous studies also show the importance of considering dosage escalation before switching biological agents in the IBD treatment. Ustekinumab has also demonstrated both efficacy and safety in the induction and maintenance of the treatment of this disease. There are certain challenges and opportunities associated with ustekinumab usage in IBD patients that require further research. Ustekinumab seems to be more cost-effective in the tumor necrosis factor (TNF)-alpha-inhibitor failure population when compared to previously used biological treatment regimes.

Among patients with ulcerative colitis, 30-50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era.

In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months.

A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse.

Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates.

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.

While the detrimental impact of negative emotions on the clinical course of inflammatory bowel disease (IBD) and quality of life has been extensively investigated, evidence for a potential impact of positive emotions is scarce.

We aim to analyse contributing factors of positive affect and their predictive value for disease course in IBD patients.

In this retrospective cohort study, epidemiological, psychosocial and IBD disease characteristics of Swiss IBD cohort study patients were analysed longitudinally.

Epidemiological, psychosocial and disease characteristics were extracted from the database of the Swiss IBD cohort study. Participants' positive emotions were assessed cross-sectionally with the seven-item Marburg questionnaire (range 1-6) addressing positive affect in different aspects of daily life. Predictors of positive emotions were identified by linear regression. The quantitative longitudinal impact of positive emotions on the further disease course was analysed using a multivariable Cox proportional hazards model.

Among 702 IBD patients, those reporting more positive emotions were found to have significantly less intense medical treatment, less pain and fewer depressive symptoms (p < 0.05). A higher percentage of variability in positive emotions was explained by pain (36%) and depressive symptoms (13%) than by epidemiological characteristics (0.3%), or characteristics of IBD and its treatment (2.4%). Patients with higher levels of positive emotions (score > 3.5) experienced longer flare-free survival, also after adjusting for confounders (adjusted hazard ratio: 0.39, p < 0.05).

The absence of pain and depressive symptoms were the strongest drivers for high positive affect. Higher scores of positive affect were associated with longer disease-free survival in IBD patients.

At present, many indicators reflect the clinical disease activity of ulcerative colitis (UC). However, commonly used inflammatory markers do not show good utility for indicating endoscopic disease activity. The purpose of this study was to evaluate high sensitivity C-reactive protein (hs-CRP), C-reactive protein to albumin ratio (CAR), inflammatory markers, and complete blood count (CBC) related parameters in patients with UC as simple, non-invasive, and independent markers of endoscopic activity (EA).

We retrospectively collected extensive data from the hospital medical records of 386 patients who presented with UC to the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China) from 2018 to 2022 January. The Mayo endoscopic score (MES) was used to evaluate endoscopic disease activity. All included patients were defined as the MES-All group; those with extensive colitis (E3) were defined as the MES-E3 group. Demographics, laboratory parameters, endoscopic results, the extent of disease, and drug history were recorded and analyzed.

For patients in the MES-All or MES-E3 group, hs-CRP, CAR, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were significantly higher in EA UC patients than in those with mucosal healing. The mean platelet volume (MPV) and lymphocyte to monocyte ratio were significantly lower in active disease than in the patient's remission (p < 0.001). ROC analysis showed that in the MES-All and MES-E3 groups, the cutoff values of hs-CRP activity under endoscopy were 5.32 mg/L (AUC 0.850, sensitivity 77.6%, specificity 81.9%) and 5.16 mg/L (AUC 0.902, sensitivity 86.9%, specificity 85.4%) respectively, and the cutoff values of CAR were 0.14 (AUC 0.853, sensitivity 76.8%, specificity 84.8%) and 0.18 (AUC 0.904, sensitivity 81.8%, specificity 89.6%) respectively. Multivariate logistic regression analysis showed that hs-CRP, CAR, NLR, and PLR identified UC EA, while decreased MPV reflected inflammatory activity in the UC mucosa.

Especially in patients with extensive colitis, hs-CRP and CAR are closely related to EA and show a higher diagnostic value compared to the related CBC parameters. The aforementioned indicators are simple and non-invasive independent markers that reflect the EA in UC.

Ulcerative colitis (UC) is a chronic disease with an increasing incidence. Recent guidelines emphasize treating toward objective targets, requiring the use of effective, steroid-sparing therapies. This review summarizes the safety and efficacy data of available therapies as well comparative effectiveness studies in order to help the reader make rational treatment decisions.

Following the approval of tumor necrosis factor alpha antagonists, we have seen recent regulatory approval of several additional biologic and small molecule agents from several therapeutic classes (integrin antagonists, interleukin 12/23 antagonists, Janus kinase inhibitors, and sphingosine-1-phosphate receptor antagonists) for UC. Randomized, controlled trials, real-world analyses, and network meta-analyses have investigated the comparative safety and efficacy of these therapies in order to help clinicians better position these therapies in clinical practice. Numerous agents are now approved for the treatment of UC. This evidence-based review will help the reader understand the important factors weighing into treatment decisions for patients with UC and enable patient education and discussion with a focus on a shared decision-making approach.

Ulcerative colitis (UC) is a chronic relapsing and remitting gastrointestinal disorder of uncertain aetiology. The last two decades have seen an expansion in the therapeutic arsenal used to treat UC. This has resulted in improved clinical remission and response rates. Nonetheless, staples in our current medical management originate from trials conducted in the early 20th century. In this review article, we aim to outline the key milestones in the history of the medical management of UC in addition to highlighting promising therapeutic developments for the future.

Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity.

We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design.

Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients.

As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.

The calcineurin inhibitor tacrolimus is reportedly effective for moderate/severe ulcerative colitis (UC); however, it is also reportedly associated with nephrotoxicity. We investigated the risk factors for tacrolimus-induced nephrotoxicity and whether renal impairment adversely affected the outcomes of tacrolimus treatment in patients with UC.

We conducted a retrospective study of 93 patients with UC who were administered tacrolimus leading to high trough levels (10-15 ng/mL) for 2 weeks and low trough levels (5-10 ng/mL) for 3 months.

Acute kidney injury (AKI) occurred in 44 patients (47.3%) during tacrolimus treatment. Of these patients, 34 (36.6%) developed AKI during the high trough phase and 17 (18.3%) developed AKI when the trough value exceeded the original target value of 15 ng/mL. Multivariate logistic regression analysis revealed that the male sex was significantly associated with AKI (p = 0.002, AOR = 4.38, 95% CI [1.69-11.3]). Clinical remission rate after 4, 8, 12, and 24 weeks of tacrolimus treatment in patients with AKI was lower than that in patients without AKI. Six patients (6.5%) had chronic kidney disease (CKD) after tacrolimus treatment completion, and all patients with CKD developed AKI during treatment. The median duration of treatment with no improvement in AKI was significantly longer in patients with CKD than in those without CKD (p = 0.016).

We revealed the risk factors for tacrolimus-induced nephrotoxicity. Renal impairment occurrence adversely affected the tacrolimus treatment outcome; therefore, it is important to carefully administer tacrolimus to prevent renal impairment.

Antibiotics have been considered to treat ulcerative colitis (UC) due to their antimicrobial properties against intestinal bacteria linked to inflammation. However, there are concerns about their efficacy and safety.

To determine whether antibiotic therapy is safe and effective for the induction and maintenance of remission in people with UC.

We searched five electronic databases on 10 December 2021 for randomised controlled trials (RCTs) comparing antibiotic therapy to placebo or an active comparator.

We considered people with UC of all ages, treated with antibiotics of any type, dose, and route of administration for inclusion. Induction studies required a minimum duration of two weeks for inclusion. Maintenance studies required a minimum duration of three months to be considered for inclusion.

We used standard methodological procedures expected by Cochrane. Our primary outcome for induction studies was failure to achieve remission and for maintenance studies was relapse, as defined by the primary studies.

We included 12 RCTs (847 participants). One maintenance of remission study used sole antibiotic therapy compared with 5-aminosalicylic acid (5-ASA). All other trials used concurrent medications or standard care regimens and antibiotics as an adjunct therapy or compared antibiotics with other adjunct therapies to examine the effect on induction of remission. There is high certainty evidence that antibiotics (154/304 participants) compared to placebo (175/304 participants) result in no difference in failure to achieve clinical remission (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06). A subgroup analysis found no differences when steroids, steroids plus 5-ASA, or steroids plus 5-ASA plus probiotics were used as additional therapies to antibiotics and placebo. There is low certainty evidence that antibiotics (102/168 participants) compared to placebo (121/175 participants) may result in no difference in failure to achieve clinical response (RR 0.75, 95% CI 0.47 to 1.22). A subgroup analysis found no differences when steroids or steroids plus 5-ASA were used as additional therapies to antibiotics and placebo. There is low certainty evidence that antibiotics (6/342 participants) compared to placebo (5/349 participants) may result in no difference in serious adverse events (RR 1.19, 95% CI 0.38 to 3.71). A subgroup analysis found no differences when steroids were additional therapies to antibiotics and placebo. There is low certainty evidence that antibiotics (3/342 participants) compared to placebo (1/349 participants) may result in no difference in withdrawals due to adverse events (RR 2.06, 95% CI 0.27 to 15.72). A subgroup analysis found no differences when steroids or steroids plus 5-ASA were additional therapies to antibiotics and placebo. It is unclear if there is any difference between antibiotics in combination with probiotics compared to no treatment or placebo for failure to achieve clinical remission (RR 0.68, 95% CI 0.39 to 1.19), serious adverse events (RR 1.00, 95% CI 0.07 to 15.08), or withdrawals due to adverse events (RR 1.00, 95% CI 0.07 to 15.08). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to 5-ASA for failure to achieve clinical remission (RR 2.20, 95% CI 1.17 to 4.14). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to probiotics for failure to achieve clinical remission (RR 0.47, 95% CI 0.23 to 0.94). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to 5-ASA for failure to maintain clinical remission (RR 0.71, 95% CI 0.47 to 1.06). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to no treatment for failure to achieve clinical remission in a mixed population of people with active and inactive disease (RR 0.56, 95% CI 0.29 to 1.07). The certainty of the evidence is very low. For all other outcomes, no effects could be estimated due to a lack of data.

There is high certainty evidence that there is no difference between antibiotics and placebo in the proportion of people who achieve clinical remission at the end of the intervention period. However, there is evidence that there may be a greater proportion of people who achieve clinical remission and probably a greater proportion who achieve clinical response with antibiotics when compared with placebo at 12 months. There may be no difference in serious adverse events or withdrawals due to adverse events between antibiotics and placebo. No clear conclusions can be drawn for any other comparisons. A clear direction for future research appears to be comparisons of antibiotics and placebo (in addition to standard therapies) with longer-term measurement of outcomes. Additionally. As there were single studies of other head-to-head comparisons, there may be scope for future studies in this area.

Messages from an Internet forum are raw material that emerges in a natural setting (i.e., non-induced by a research situation).

The FLARE-IBD project aimed at using an innovative approach consisting of collecting messages posted by patients in an Internet forum and conducting a machine-learning study (data analysis/language processing) for developing a patient-reported outcome measuring flare in inflammatory bowel disease meeting international requirements.

We used web-based and machine learning approaches, in the following steps. 1) Web-scraping to collect all available posts in an Internet forum (23 656 messages) and extracting metadata from the forum. 2) Twenty patients were randomly assigned 50 extracted messages; participants indicated whether the message corresponded or not to the flare phenomenon (labeling). If yes, participants were asked to identify excerpts from the text they considered significant flare markers (annotation). 3) The set of annotated messages underwent a vocabulary analysis.

The phenomenon of flare was circumscribed with the identification of 20 surrogate flare markers classified into five dimensions with their frequency within extracted labeled data: impact on life, symptoms, extra-intestinal manifestations, drugs and environmental factors. Web-based and machine-learning approaches met international recommendations to inform the content and structure for the development of patient-reported outcomes.

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn's disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases.

Infliximab (IFX) and calcineurin inhibitors (cyclosporine [CYS] and tacrolimus [TAC]) were considered as rescue therapy in steroid-refractory ulcerative colitis (UC). The objective of our study was to perform a meta-analysis evaluating the short-term and long-term efficacy and safety of IFX and calcineurin inhibitors in steroid-refractory UC.

We systematically searched the databases from inception to September 2020 that evaluated IFX, CYS, and TAC in steroid-refractory UC. The primary outcome was the response rates, remission rates, mucosal healing rates, and colectomy rates after therapy initiation. The secondary outcomes were the rates of adverse events (AE), serious adverse events (SAE), and mortality. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated.

Nineteen studies comprising 1323 Acute severe ulcerative colitis (ASUC) patients were included in the meta-analysis. Among the non-randomized studies, a significantly higher therapeutic response rate was seen with IFX treatment, with a pooled OR of 3.15 (95% CI 2.26-4.40). Among non-randomized studies, IFX was associated with a significantly lower first-year OR (0.46 [95% CI 0.27-0.79]), second-year (OR 0.53 [95% CI 0.28-0.97]), third-year (OR 0.43 [95% CI 0.24-0.75]) colectomy rate. But the randomized controlled trials (RCTs) did not suggest any difference between IFX and CYS as rescue therapies for steroid-refractory UC. There were no significant differences among IFX, CYS, and TAC in the rates of AE, SAE, or mortality.

Our meta-analysis suggested a better treatment response rate and lower risk of colectomy in the first, second and third year, with IFX, compared with CYS in steroid-refractory UC patients. There was no significant difference among IFX and calcineurin inhibitors in AE, SAE, and mortality.

Acute severe ulcerative colitis (ASUC) is a life-threatening condition that requires timely referral for therapy. Sarcopenia has been associated with clinical outcomes of inflammatory bowel disease (IBD). This study investigated the role of sarcopenia in predicting the clinical course of ASUC.

This retrospective cohort study included ASUC patients with abdominal CT scans. Univariate and multivariable regression analyses were performed to identify a practical predictive index for the clinical course of ASUC.

Of 233 included patients, 151 had intravenous corticosteroid (IVS) failure, among whom 32 received surgery without medical rescue therapy. Fifty patients underwent colectomy after medical rescue therapy failure. Of these 82 surgical patients, 42 suffered postoperative complications. Multivariable regression analysis showed that sarcopenia remained an independent risk factor for IVS failure (OR=2.969; 95% CI, 1.547-5.701; p = 0.001), colectomy after medical rescue therapy failure (OR=3.411; 95% CI, 1.147-10.141; p = 0.027), and postoperative complications after colectomy (OR=4.157; 95% CI, 1.364-12.667; p = 0.012). During follow-up, patients with colectomy after first-line treatment had a lower comprehensive complication index and better health-related quality of life.

Sarcopenia is useful in predicting the clinical course and postoperative outcomes of ASUC.

We evaluated the association between endoscopic scores of colonic inflammation and fecal calprotectin (FC), fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP) in patients with ulcerative colitis (UC). Endoscopic scores reflecting the most severe lesion [maximum Mayo Endoscopic Subscore (M-MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)] and those reflecting the inflammation of the entire colon [sum of MES (S-MES) and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS)] were evaluated. FC, FIT, and CRP were measured, and their association with the four endoscopic scores was evaluated. Endoscopic scores of 78 complete colonoscopies (66 UC patients) were evaluated using the three biomarkers. FC and CRP tended to correlate more strongly with S-MES and UCCIS than with M-MES and UCEIS. In the M-MES 0, 1 group, compared to CRP, FC and FIT showed stronger correlations with S-MES and UCCIS. Conversely, in the M-MES 2, 3 group, only CRP was significantly correlated with each descriptor. CRP more strongly reflects colon-wide mucosal inflammation than FC and allows reliable assessment of inflammation throughout the colon in active UC.

Subtotal colectomy (STC) is performed for severe acute and refractory colitis. The diagnosis can be difficult even after the surgery when colectomy specimen has overlapping features of ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to evaluate the rate of postoperative diagnostic revision to CD after surgery and determine predictor factors.

Retrospective study of 110 patients who underwent STC (2005-2018).

Preoperative diagnosis comprised UC = 80 (73%), CD = 11 (10%), and unclassified colitis (IBDU = 19, 17%). Initial diagnosis of IBDU and UC was modified to CD in 6 patients (6%) after STC. The final diagnosis after the follow-up of 10 ± 6 years switched from CD for 8 patients (9%). The multivariate analysis showed that patients with a colitis evolving for less than 10 years and initial diagnosis of IBDU were the two independent factors associated with an increased risk of diagnosis change to CD (p = 0.03; p = 0.016). At the end of the follow-up, 15 patients (14%) had a definitive stoma.

In patients with IBD, attention must be paid to determine the right restorative strategy to patients with an evolution of the disease less than 10 years or with IBDU who are more at risk to have a diagnosis change to CD after STC.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a novel biomarker reflecting endoscopic activity in ulcerative colitis (UC). However, there are no studies investigating the efficacy of PGE-MUM as a biomarker for predicting relapse. We investigated whether PGE-MUM can predict clinical relapse of UC.

The measurement of PGE-MUM and endoscopic evaluation were performed in 70 patients with UC in clinical remission. The optimal cutoff values predicting relapse and relapse-free rate were analyzed.

Sixteen patients (22.9%) relapsed during the 12-month follow-up. The median PGE-MUM value of relapsed patients at entry was significantly higher than that of patients in clinical remission (P = 0.008). The cutoff value of PGE-MUM predicting future relapse was 25.2 μg/g Cr by receiver-operating characteristic (ROC) analysis, and the area under the ROC curve was 0.721 (95% confidence interval: 0.556-0.886). The relapse-free rate of patients with PGE-MUM ≥25.2 μg/g Cr was significantly lower than that in patients with PGE-MUM <25.2 μg/g Cr (log-rank test: P < 0.001). The ROC analysis of UC patients with disease duration more than 1-8 years showed that duration of more than 5 years had the largest area under the ROC curve 0.821 (95% confidence interval: 0.583-1.000) and that the optimal cutoff value was 26.3 μg/g Cr.

PGE-MUM is a reliable biomarker for predicting future relapse, particularly in UC patients with long-disease duration.

Ulcerative colitis (UC) is a chronic disease that can present at various stages of disease activity and severity. Traditionally, severity scoring has focused on disease activity during a single moment with various tools, including patient-reported symptoms, as well as clinical, laboratory-based, endoscopic, histologic, and imaging variables. Optimal delivery of care depends on the accurate assessment of disease severity, which must take longitudinal variables into account. This article reviews the history of severity scoring in UC and provides a concise, clinically oriented approach to assessing disease severity.

Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies.

We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration.

A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5-10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events.

The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively.

Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

The effects of ulcerative colitis (UC) duration on biomarker accuracy are unknown. We investigated the effects of UC duration on the predictive accuracy of biomarkers including immunochemical fecal occult blood test (FOBT, also known as FIT), prostaglandin E-major urinary metabolite (PGE-MUM), and C-reactive protein (CRP).

We divided 133 samples into groups based on disease duration. Clinical and endoscopic remission was defined as Lichtiger's clinical activity index (CAI) of ≤ 4, Mayo endoscopic subscore (MES) of 0, and UC endoscopic index of severity (UCEIS) of ≤ 1.

FIT results were significantly correlated with all activity scores when the disease duration was < 4 years. When the disease duration was ≥ 4 years, FIT results were significantly correlated with the CAI and MES but not with UCEIS. When the disease duration was ≥ 5 years, FIT and CAI were significantly correlated, whereas FIT and MES or FIT and UCEIS did not show any correlation. When the duration was ≥ 4 years, PGE-MUM and CRP showed a significant correlation with CAI, MES, and UCEIS. Receiver operating characteristic curve analysis of biomarker data for predicting endoscopic remission showed that the accuracy of FIT was superior to that of PGE-MUM and CRP in the < 4-year group.

FIT is an accurate biomarker reflecting the endoscopic score until 4 years in patients with UC. However, owing to the increased number of false negatives, the usefulness of FIT may decline after 4 years. Hence, evaluation of UC in combination with other biomarkers is recommended.

Immune checkpoint inhibitors are a novel class of cancer treatment that have improved outcomes for a subset of cancer patients. They work by antagonising inhibitory immune pathways, thereby augmenting immune-mediated antitumour responses. However, immune activation is not cancer-specific and often results in the activation of immune cells in non-cancer tissues, resulting in off-target immune-mediated injury and organ dysfunction. Diarrhoea and gastrointestinal tract inflammation are common and sometimes serious side-effects of this type of therapy. Prompt recognition of gastrointestinal toxicity and, in many cases, rapid institution of anti-inflammatory or biologic therapy (or both) is required to reverse these complications. Management of organ-specific complications benefits from multidisciplinary input, including engagement with gastroenterologists for optimal management of immune checkpoint inhibitor-induced enterocolitis. In this British Society of Gastroenterology endorsed guidance document, we have developed a consensus framework for the investigation and management of immune checkpoint inhibitor-induced enterocolitis.

Prostaglandin E-major urinary metabolite (PGE-MUM) may be a novel biomarker for evaluating disease activity in ulcerative colitis (UC). We compared its usefulness to that of the fecal immunochemical occult blood test (FIT).

PGE-MUM and FIT measurements were performed of 92 urinary and fecal samples obtained from 60 patients with UC. Endoscopic activity was determined by Mayo endoscopic subscore (eMayo) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score.

PGE-MUM levels and FIT results showed a significant correlation with respect to eMayo (P <  0.001 and P < 0.001, respectively), and there was a significant difference in PGE-MUM values between the groups below eMayo1 and above eMayo2 (P = 0.012). Both biomarkers were significantly correlated with the UCEIS score (P < 0.001 and P < 0.001, respectively), and the PGE-MUM values were significantly different between groups below UCEIS1 and above UCEIS2 (P = 0.012). PGE-MUM and FIT were significantly correlated with eMayo in the group with a disease duration < 5 years (P = 0.041 and P < 0.001, respectively). Although PGE-MUM and eMayo differed significantly between groups over 5 years (P = 0.012), FIT was not correlated with eMayo (P = 0.101).

PGE-MUM is useful as a biomarker as FIT for evaluating the endoscopic activity, particularly in long-term affected patients with UC.