Medical management of ulcerative colitis (UC) and crohn's sisease (CD) is complex. While there is significant overlap in medical therapies used for UC and CD, there remain few distinct differences in their management. The overall goals of therapy are to achieve disease remission, prevent complications, decrease the need for surgical interventions, and restore patients' quality of life. In the current article, we discuss currently available therapies and their mechanisms, limitations and side effects, followed by a comprehensive discussion of key consideration points in regards to the medical management.

Surgical site infection (SSI) is a critical issue in colorectal surgery because it decreases postoperative patient quality of life. The rate of SSI in patients with ulcerative colitis (UC) receiving immunosuppressive therapy is particularly high, suggesting that the SSI rate may increase with the introduction of biologic agents.

UC patients who underwent two-stage restorative proctocolectomy at our institution between April 2012 and December 2023 were included in this study. Clinical characteristics were analyzed and compared between an SSI group and a non-SSI group; possible risk factors for SSIs were also analyzed. Additionally, the following anti-SSI measures adopted at our hospital were included as explanatory variables: laparoscopic surgery, oral antibiotic prophylaxis and change of surgical instruments before wound closure.

In total, 501 UC surgical patients were included. The incidence of overall SSIs was 45/501 (8.9%). The rates of incisional SSIs and organ/space SSIs were 26/501 (5.1%) and 30/501 (5.9%), respectively. Oral antibiotic prophylaxis was identified as a risk factor for overall SSIs (odds ratio: 0.45, 95% CI 0.20-0.99, p = 0.02), incisional SSIs (odds ratio: 0.34, 95% CI 0.11-1.03, p = 0.03) and organ/space SSIs (odds ratio: 0.35, 95% CI 0.12-0.98, p = 0.04). The use of biologic and immunosuppressive agents was not associated with any SSIs.

Nonadministration of oral antibiotic prophylaxis was identified as a risk factor for SSIs. Oral antibiotic prophylaxis before restorative proctocolectomy may improve the postoperative quality of life of UC patients by preventing SSIs.

Considering the role of leukotrienes in inflammatory pathways, and owing to the anti-leukotrienes effect of montelukast, in the present clinical trial, we aimed to assess the effect of montelukast on remission maintenance in patients with ulcerative colitis (UC).

In the present double-blind randomized controlled clinical trial, 222 volunteer UC patients on high-dose corticosteroid and montelukast were recruited. The patients received 10 mg of montelukast (98 patients) or placebo (124 patients) for 22 weeks. Simultaneously, the prednisolone dose was tapered. The patients were followed up eight more weeks post-interventions. The primary efficacy of the treatment was remaining in remission.

194 patients completed this study. During the study, relapse occurred in 108 patients, 32 patients in the montelukast group and 76 patients in the placebo group. There were significant differences between groups regarding the relapse-free period (intervention group mean: 27.25 95% CI: 26.17-28.32 weeks and placebo group mean: 20.88; 95% CI: 19.36, 20.40 weeks, P < 0.001). At the end of the intervention period and six weeks' post-intervention, the mean partial Mayo score, and inflammatory biomarkers were significantly lower in the montelukast group compared with the placebo group. The frequency of patients with high fecal calprotectin levels was significantly higher in the placebo group compared with the montelukast Group.

The findings indicated that compared with placebo, montelukast had a significant positive effect on remission maintenance in UC patients who were in the steroid-tapering phase of therapy.

IRCT20121212011738N3.

The past decade has seen a substantial increase in the number of randomized controlled trials (RCTs) conducted in inflammatory bowel disease (IBD). Randomized controlled trials are the gold standard method for generating robust evidence of drug safety and efficacy but are expensive, time-consuming, and may have ethical implications. Observational studies in IBD are often used to fill the gaps in evidence but are typically hindered by significant bias. There are several approaches for making statistical inferences from observational data with some that focus on study design and others on statistical techniques. Target trial emulation is an emerging methodological process that aims to bridge this gap and improve the quality of observational studies by applying the principles of an ideal, or "target," randomized trial to routinely collected clinical data. There has been a rapid expansion of observational studies that have emulated trials over the past 5 years in other medical fields, but this has yet to be adopted in gastroenterology and IBD. The wealth of nonrandomized clinical data available through electronic health records, patient registries, and administrative health databases afford innumerable hypothesis-generating opportunities for IBD research. This review outlines the principles of target trial emulation, discusses the merits to IBD observational studies in reducing the most common biases and improving confidence in causality, and details the caveats of using this approach.

While corticosteroids are not recommended for maintenance of remission in inflammatory bowel disease (IBD), they are quite effective for the induction of remission for both Crohn's disease (CD) and ulcerative colitis (UC). We aimed to evaluate if a delay in starting corticosteroids after presentation to the hospital for an acute IBD exacerbation increased the likelihood of poor outcomes.

Retrospective cohort study of IBD-related hospitalizations from 7 area hospitals in Austin, Texas between 2015 and 2020. Patients were included if admitted for an IBD flare and received corticosteroids. CD with intra-abdominal abscesses were excluded. Primary outcomes were length of stay (LOS), ICU stay, IBD-related surgery, and mortality.

Of 478 inpatients, 311 (65%) received corticosteroids within 12 h of arrival. ICU stays (4.2% vs. 5.4%, p = 0.88, early vs. late corticosteroids) and inpatient mortality (1.0% vs. 1.8%, p = 0.75) were not significantly different between groups. However, after adjustment for confounders, LOS (4.7 vs. 5.8 days, p = 0.027) was significantly shorter and IBD-related surgery (3.5% vs. 7.2%, p = 0.048) was reduced for those receiving corticosteroids early. On subgroup analysis, these findings remained significant only for patients with CD and not UC.

For patients admitted with IBD flares without associated abscess, there was an increased LOS and increased risk for IBD-related surgery if corticosteroid therapy was delayed > 12 h after arrival. Guidelines recommend treating acute flares without delay, but guidance on specifics of timing is absent. Our data suggests that treatment should be started within 12 h of presentation, particularly for those with CD.

Inflammatory bowel disease (IBD) is characterized by disruptions in the gut microbiome. While most studies on gut dysbiosis in IBD rely on sequencing-based methods, we employed a streamlined culturomics approach to obtain a more comprehensive understanding of gut microbiota imbalance in patients with IBD that may not be captured by sequencing alone. A total of 367 bacteria were identified at the species level, including 211 species from ulcerative colitis patients, 164 species from Crohn's disease (CD) patients, and 263 species from healthy individuals. Consistent with our 16S rRNA gene amplicon sequencing results, a significant decrease in microbial diversity and a severe imbalance, especially in CD patients, were also observed in the culture-based analysis. Our culturomics approach provided additional insights, highlighting dysbiosis in unique anaerobic and Gram-negative species in CD patients. Moreover, species-level findings for Bifidobacterium and Enterobacterales emphasized specific species expansions in IBD patients. Notably, Mediterraneibacter gnavus, Thomasclavelia ramosa, Parabacteroides merdae, and Collinsella aerofaciens are of particular clinical interest due to their correlation with inflammatory biomarkers. This comprehensive analysis underscores the value of integrating a culture-based approach with a genome-based approach to provide complementary insights and therapeutic targets in IBD.

The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.

Efferocytosis is the process by which various phagocytes clear apoptotic cells. In recent years, an increasing body of evidence has emphasized the importance of efferocytosis in maintaining internal homeostasis. Intestinal macrophages play a crucial role in modulating intestinal inflammation and promoting tissue repair. Inflammatory bowel disease (IBD) is a chronic, progressive, and relapsing condition, primarily marked by the presence of ulcers in the digestive tract. The exact mechanisms underlying IBD are not yet fully understood, and current treatment approaches mainly aim at repairing the damaged intestinal mucosa and reducing inflammatory responses to ease symptoms.This article provides new perspectives on IBD treatment and clinical management by examining the expression of macrophage efferocytosis-related molecules, the effects of efferocytosis on IBD development, the various roles of macrophage efferocytosis in IBD, and treatment strategies for IBD that focus on efferocytosis.

Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory bowel disease caused by multiple causes. Lymphocytes migration is involved in the pathogenesis of IBD. The purpose of this study was to evaluate whether there were differences in blood lymphocytes levels between IBD patients in clinical remission and healthy people.

A total of 94 Crohn's disease (CD) and 20 ulcerative colitis (UC) patients were included in this study. Ninety-four people who underwent physical examination in our hospital were randomly selected as controls. We analyzed whether there were differences in white blood cell count, neutrophil count, neutrophil percentage, lymphocyte count, lymphocyte percentage between CD patients, UC patients, and healthy people.

There were significant differences in lymphocyte count (P < 0.001), lymphocyte percentage (P < 0.001), neutrophil count (P = 0.038), and neutrophil percentage (P < 0.001) between CD patients and normal people, but no statistically significant differences in sex (P = 0.216), age (P = 0.745), and white blood cell count (P = 0.757). UC patients had significant differences in white blood cell count (P = 0.005), lymphocyte count (P = 0.010), and neutrophil count (P = 0.023), but no difference in lymphocyte percentage (P = 0.968) and neutrophil percentage (P = 0.461).

The white blood cell count of CD patients was not significantly different from that of normal people, but the lymphocyte count and lymphocyte percentage were significantly different from that of healthy people. Similar results were not found in UC patients.

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.

Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC.

A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed.

We included 158 patients; 34 (21.5%) underwent colectomy during hospital admission and 41 (25.9%) within a year. On multivariable analysis, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P = 0.005), and biologic use at admission (OR 3.31, 95%CI 1.14-9.63, P = 0.028) were associated with an increased risk of 1-year colectomy. Conversely, mesalamine use at admission decreased this risk (OR 0.31, 95%CI 0.13-0.72, P = 0.006). Other risk factors included recent UC-related hospitalization (< 1 year of admission), higher bowel movement frequency after 3 days of treatment, low hemoglobin and albumin levels, and elevated CRP. Infliximab treatment was associated with decreased risk of urgent (OR 0.30, 95%CI 0.13-0.73, P = 0.007) and 1-year colectomy (OR 0.31, 95%CI 0.14-0.73, P = 0.007).

In patients with ASUC, prior anti-TNF exposure is linked to a higher risk of both short- and long-term colectomy, while recycling infliximab may reduce colectomy risk.

The differences in the clinical course of Crohn's disease (CD) and ulcerative colitis (UC) among Asian countries remain unknown. Thus, we compared the clinical characteristics, treatment, and one-year outcomes of newly diagnosed inflammatory bowel disease (IBD) patients between Vietnam and Korea.

A retrospective cohort study was conducted at seven tertiary hospitals in these countries between January 2020 and January 2021. Data on demographics, diseases, treatment, and outcomes during 1 year after diagnosis were collected.

Among 225 patients (60 from Vietnam and 165 from Korea), 140 and 85 were diagnosed with UC and CD, respectively. Severe activity (p < 0.01) and extensive colitis (p < 0.01) in UC, along with complicated behavior in CD (p < 0.01), were more frequently observed in Vietnamese patients compared to Korean patients. The proportion of UC patients using corticosteroids (p < 0.01), immunomodulators (p < 0.01), and biologics (p = 0.026) was significantly higher in Vietnam. In contrast, the proportion of UC patients using topical mesalamine (p < 0.01) was significantly higher in Korea. The intervals from CD diagnosis to biologic therapy initiation (p = 0.04), as well as from UC diagnosis to corticosteroid (p < 0.01), immunomodulator (p < 0.01), and biologic therapy (p < 0.01) commencement, were significantly shorter in Vietnamese patients compared to Korean patients. However, the proportions of endoscopic healing and complications at 1-year follow-up did not significantly differ between the countries (p > 0.05).

Although Vietnamese IBD patients had higher baseline clinical and phenotypic severity than their Korean counterparts, no significant differences in short-term outcomes were observed, potentially reflecting the impact of the higher rate and early biologic usage in Vietnamese patients.

Endoscopy plays a key role in diagnosis, monitoring of disease activity, assessment of treatment response, dysplasia surveillance, postoperative evaluation, and interventional therapy for patients with inflammatory bowel disease (IBD). Clinical practice patterns in the endoscopic management of IBD vary. A panel of experts consisting of IBD specialists, endoscopists, and GI pathologists participated in virtual conferences and developed this modified Delphi-based consensus document to address endoscopic aspects of IBD management.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician-patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice.

Several conditions exist that do not have their own unique diagnosis code in widely-used clinical terminologies, making them difficult to track and study. Acute severe ulcerative colitis (ASUC) is one such condition. There is no automated method to identify patients admitted for ASUC from observational data, nor any specific billing or diagnosis code for ASUC. Accurate, automated, large-scale identification of hospital admissions for non-coded conditions like ASUC may enable further research into them.

We performed a retrospective cohort study of patients with a history of ulcerative colitis (UC) admitted to a single academic institution from 2014-2019. Clinicians at our institution performed a chart review of these admissions to determine if each was due to a true episode of ASUC or not. Logistic regression, random forest (RF), and support vector machine (SVM) models were trained upon administrative claims data for all admissions.

268 ASUC admissions and 3,725 non-ASUC admissions among UC patients were included. Our RF model exhibited the best performance, correctly classifying 95.5% of admissions as either ASUC or non-ASUC, with a validation AUROC of 0.96 (95% CI 0.94-0.98; AUPRC 0.73). The model had a sensitivity of 81.5% and specificity of 96.5%. The five most important features in the model were endoscopy of sigmoid colon, length of stay, age, endoscopy of rectum, and abdominal x-ray.

There is currently no modality by which ASUC, which does not have its own unique diagnosis code, can be identified from claims databases in a scalable fashion for research or clinical purposes. We have developed a machine learning-based model that identifies clinically significant ASUC and reliably distinguishes them from admissions for non-ASUC reasons among UC patients. The ability to automatically curate large, accurate datasets of non-coded conditions like ASUC episodes can serve as the basis of large-scale analyses to maximize our ability to learn from real-world data, enable future research, and better understand these diseases.

Ulcerative colitis is a chronic inflammatory condition of the colon driven by aberrant immune activation. Although advanced medical therapies form the cornerstone of ulcerative colitis management, unmet needs include failure to induce and sustain remission in a substantial proportion of patients and in managing acute severe ulcerative colitis. We review new treatment strategies that might improve patient outcomes in the management of moderate-to-severe ulcerative colitis.

A literature search was conducted using the PubMed database, including studies published from inception to October 2024, selected for their relevance. Recognizing current limitations, this article reviews strategies to improve treatment outcomes in ulcerative colitis using advanced therapies. These approaches include early treatment initiation, dose optimization, positioning newer agents as first-line therapies, combination therapy, targeting novel therapeutic endpoints, and the management of acute severe ulcerative colitis.

The strategies discussed may contribute to establishing new standards of care aimed at achieving long-term remission and enhancing patient outcomes. Personalized therapy, which tailors treatment based on individual disease characteristics and risk factors, is anticipated to become a critical aspect of delivering more effective care in the future.

Validated scoring methods such as the Mayo Clinic Endoscopic Subscore (MCES) evaluate ulcerative colitis (UC) severity at the worst colon segment, without considering disease extent. We present the Ulcerative Colitis Severity Classification and Localized Extent (UC-SCALE) algorithm, which provides a comprehensive and automated evaluation of endoscopic severity and disease extent in UC.

Ulcerative Colitis Severity Classification and Localized Extent consists of 3 main elements: (1) a quality filter selecting readable images (frames) from colonoscopy videos, (2) a scoring system assigning an MCES to each readable frame, and (3) a camera localization algorithm assigning each frame to a location within the colon. Ulcerative Colitis Severity Classification and Localized Extent was trained and tested using 4326 sigmoidoscopy videos from phase III Etrolizumab clinical trials.

The high agreement between UC-SCALE and central reading at the level of the colon section (𝜅 = 0.80), and the agreement between central and local reading (𝜅 = 0.84), suggested a similar inter-rater agreement between UC-SCALE and experienced readers. Furthermore, UC-SCALE correlated with disease activity markers such calprotectin, C-reactive protein and patient-reported outcomes, Physician Global Assessment and Geboes Histologic scores (rs 0.40-0.55, ps < 0.0001). Finally, the value of using UC-SCALE was demonstrated by assessing individual endoscopic severity between baseline and induction.

Our fully automated scoring system enables accurate, objective, and localized assessment of endoscopic severity in UC patients. In addition, we provide a topological representation of the score as a marker of disease severity that correlates highly with clinical metrics. Ulcerative Colitis Severity Classification and Localized Extent reproduces central reading and holds promise to enhance disease severity evaluation in both clinical trials and everyday practice.

Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.

In chronic inflammatory bowel diseases (IBD), severe flares are characterized by intense inflammatory activity and a high disease burden for patients. Treatment addresses both short-term goals (e.g., symptom reduction, prevention of complications) and long-term goals (sustained clinical steroid-free remission and healing of inflammatory lesions, known as "mucosal healing").

To present evidence-based, targeted diagnostics and stepwise treatment of severe flares in Crohn's disease (CD) and ulcerative colitis (UC), in order to prevent complications, including mortality, and to achieve rapid remission.

Selective literature review, including German and European guidelines for the treatment of severe flares.

After ruling out complications (e.g., infections, strictures, abscesses, toxic megacolon), based on a structured assessment of disease severity, intravenous steroid therapy is indicated in severe acute flares for both CD and UC, which should lead to improvement within the first 72 h. If no improvement occurs, medical therapy must be intensified. Various therapeutics, including biologics targeting tumor necrosis factor (TNF)-α, α4ß7 integrins, interleukin (IL)-12/23 or IL-23, as well as Janus kinase (JAK) inhibitors, sphingosine 1‑phosphate receptor (S1PR) modulators, and calcineurin inhibitors, are available today, but there is no clear algorithm preferring one drug for CD or UC. Instead, treatment should be selected based on approvals, the patient's medical history, prior treatment, risk profile, and potential complications. Surgical options must always be considered as part of close interdisciplinary care.

To compare the long-term safety and efficacy of Adalimumab (ADA) and Infliximab (IFX) agents in biologic-naive patients with Ulcerative colitis (UC).

The key focus was on specific outcomes such as the requirement of hospitalization due to UC, colectomy, steroid administration, and severe infections that led to the discontinuation of therapy.

Anti-TNF treatment was initiated in 208 of the 475 patients with ulcerative colitis. The final study population consisted of 86 biologic-naive patients with UC, including 41 treated with IFX and 45 treated with ADA. No significant differences in treatment details, baseline Mayo scores, risk factors, or demographic features were observed. The ADA group displayed a significantly increased need for steroids (44.4%) compared to the IFX group (14.6%). The UC-associated hospitalization, colectomy, and serious infections were similar between the ADA and IFX groups. Similar outcomes were observed with IFX or ADA as monotherapy or in combination with immunomodulators. The survival analysis revealed IFX had a longer time to secondary loss of response compared to ADA, however, without statistical significance (72.5% versus 46.7%, P = 0.057).

Our results hint at the likelihood of IFX and ADA presenting similar clinical outcomes as first-time agents in UC. Nonetheless, the need for steroids with ADA should be taken into consideration.

The role of various histologic scores in predicting outcomes in acute severe ulcerative colitis (ASUC) is unexplored.

Consecutive patients of ASUC undergoing sigmoidoscopy and histological assessment by two independent pathologists for Simplified Geboes score (SGS), Robarts Histopathology Index (RHI) and Nancy histological index (NHI)] were included. Primary outcome was the role of histology in predicting need for second-line therapy or colectomy.

Of 82 patients with ASUC (mean age: 36 years, males 47.5 %), non-response to steroids was observed in 27 (32.9 %) of cases. Sixteen patients required second-line drug therapy and 8 required colectomy. There was no significant association between the need for second-line therapy or colectomy and the baseline histological scores [NHI (p = 0.61), SGS (p = 0.116) and RHI (p = 0.109)]. All three scores performed poorly to predict the need for second-line treatment or colectomy within 28 days. There was no significant association between histological scores and steroid response (NHI (p = 0.796), SGS (p = 0.57) and RHI (p = 0.941)]. All three scores had a strong positive correlation observed between each other but not with endoscopic Mayo score.

The three histologic scores (SGS, RHI and NHI) performed poorly in prediction of need for second-line treatment or colectomy in ASUC. Future studies should study the impact of histologic assessment on long term outcomes in ASUC.

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.

There are several available endoscopic scoring systems that are designed to assess disease activity in inflammatory bowel disease. The most widely known is the Mayo endoscopic subscore for ulcerative colitis. These schemas are not routinely used in clinical practice, largely due to their complexity or lack of granularity, although they are standard for outcomes measurement in large clinical trials. While some schemas have been validated using independent cohorts, there is high inherent interobserver variation. Furthermore, derivation of these scoring systems has been subject to selection bias and limited challenge bias.

Acute severe ulcerative colitis (ASUC) represents a medical emergency associated with high mortality and morbidity. While corticosteroids are the primary treatment, cases that are unresponsive often require rescue therapy with either infliximab or cyclosporine to reduce the rate of colectomy. Janus kinase inhibitors, such as tofacitinib and upadacitinib, are a highly efficacious therapy with rapid induction of clinical response in moderate to severe ulcerative colitis (UC). Limited data are available on its use on ASUC. We present the first case utilizing upadacitinib as sequential medical rescue therapy in ASUC as well as intestinal ultrasound as a useful tool for disease and response monitoring.

A 69-year-old female who presented with corticosteroid-refractory ASUC partially responded to dose-intensified infliximab and finally achieved clinical remission with upadacitinib. This resulted in swift clinical remission and significant improvement in her mucosal inflammation on intestinal ultrasound.

This successful intervention not only avoided colectomy but demonstrated sustained clinical and sonographic remission 16 weeks of post-treatment. Upadacitinib, with its rapid action and efficacy, shows promise in ASUC and should be supported by registration trials and real-world studies. Despite successful outcomes in this case, further validation and long-term data are necessary.

Venous thromboembolism is a serious complication during and following hospitalization with acute severe ulcerative colitis (ASUC). We evaluated serial thrombotic profiles of patients with ASUC from the point of hospitalization up to 12 weeks postdischarge and compared these with control patients with quiescent ulcerative colitis.

Twenty-seven patients with ASUC and 25 control patients with quiescent ulcerative colitis were recruited. Thrombin generation (endogenous thrombin potential), rotational thromboelastometry (EXTEM and FIBTEM maximum clot firmness), procoagulant factors, anticoagulant factors, and fibrinolytic markers were assessed for those with ASUC on admission (Day 1), Day 5, 4 weeks, and at 8-12 weeks. These assessments were performed on a single occasion for control patients.

Endogenous thrombin potential and maximum clot firmness were significantly elevated in patients with ASUC compared with control subjects and remained significantly elevated for 4 weeks and for 8-12 weeks after admission (P < .05), respectively. Von Willebrand factor antigen, factor VIII, Clauss fibrinogen concentration, and platelet count were significantly increased from presentation to 8-12 weeks and are likely to account for changes in the global hemostatic profile.

Global measures of hemostasis demonstrated that patients with ASUC were prothrombotic compared with control subjects with quiescent colitis. This difference was maintained 8-12 weeks after the initial presentation, supporting clinical observations that patients with ASUC have an elevated risk of venous thromboembolism after hospital discharge.

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

Background: Bilberries are effective in inducing clinical, endoscopic, and biochemical improvement in ulcerative colitis (UC) patients. The aim of this study was to investigate the efficacy of anthocyanin-rich extract (ACRE), the bioactive ingredient of bilberries, in a controlled clinical trial in moderate-to-severe UC. Methods: A multi-center, randomized, placebo-controlled, double-blind study with a parallel group was conducted. Initially, the study was planned for 100 patients; nevertheless, it prematurely ended due to COVID-19. Patients had moderate-to-severe active UC at screening (a Mayo score of 6-12, an endoscopic sub-score ≥ 2) and were randomized at baseline. The primary endpoint was a clinical response (week 8, a total Mayo score reduction ≥ 3 points). Fecal calprotectin (FC) and a centrally read endoscopic response were among the secondary endpoints. Results: Out of 48 patients (6 Swiss centers), 34 were randomized. Eighteen ACRE and eight placebo patients could be analyzed (per protocol set). Half (9/18) of ACRE patients and 3/8 of placebo patients responded clinically (p = 0.278). An improvement in the Mayo score was observed in the ACRE arm (77.8% vs. 62.5% placebo). FC dropped from 1049 ± 1139 to 557 ± 756 μg/g for ACRE but not for the placebo group (947 ± 1039 to 1040 ± 1179; p = 0.035). Serious adverse events were rare. Conclusions: ACRE treatment did not yield significant superiority to the placebo. Furthermore, the placebo response was unusually high. Moreover, there was a significant calprotectin decrease at the end of treatment, indicative of ACRE efficacy in UC.

Background Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is often considered the preferred surgical treatment for ulcerative colitis. This study was conducted to investigate the early and late complications of ileal pouch-anal anastomosis in patients with ulcerative colitis, as well as the factors associated with these complications. Methodology All relevant clinical and operative data of patients (n = 101) who underwent IPAA for ulcerative colitis between January 1995 and December 2018 were retrieved from a prospectively maintained database. Early complications, various late complications, and their predictive factors were studied. Results A total of 101 patients underwent IPAA. Early complications (≤30 days) occurred in 72 (71.3%) patients, mostly Clavien-Dindo grades 1 and 2. No significant risk factors were associated with early complications. Among the late complications, pouchitis was the most common complication (n = 37, 36.6%), followed by anastomotic stricture (n = 27, 26.7%). Pouch failure was seen in 11 (10.9%) patients. No significant factors were found to be associated with the development of pouchitis. Pelvic sepsis (odds ratio (OR) = 2.704, 95% confidence interval (CI) = 1.041-7.022, p = 0.041) and handsewn anastomosis (OR = 3.943, 95% CI = 1.093-14.229, p = 0.036) were significantly related to the development of anastomotic stricture and pouch-vaginal fistulae, respectively. Conclusions The most common early and late complications following IPAA were pelvic sepsis and pouchitis, respectively. These complications were managed successfully with an acceptable pouch failure rate. No predictive factor was found to be significant with early complications. However, pelvic sepsis and hand-sewn anastomosis were associated with stricture formation and pouch vaginal fistulae, respectively.

Drug sustainability (DS), a surrogate marker for drug efficacy, is important, especially when aiming for precision medicine. However, it lacks reliable prediction methods.

To develop and externally validate a web-based artificial intelligence(AI)-derived tool for predicting DS of infliximab and vedolizumab in patients with moderate-to-severe Ulcerative Colitis (UC).

Data from three Israeli centers included infliximab or vedolizumab patients treated for >54 weeks. Sustainability meant no corticosteroids, hospitalizations or surgeries. Machine learning techniques predicted >54-week and overall DS using baseline clinical data.

The model was developed using data from 246 patients from Rabin Medical Center and externally validated on 67 patients from Rambam Health Care Campus and Sheba Medical Center. No significant difference in DS was observed across the datasets. Most patients were biologic-naïve and primarily treated with vedolizumab. The model performed well, with an area under the ROC curve of 0.86, and showed good accuracy (65.5 %-76.9 %) across the test sets.

The study introduces a novel, AI-based tool for predicting >54-week DS of infliximab and vedolizumab in moderate-to-severe UC, using baseline parameters. This can aid clinical decision-making in the framework of precision medicine, promising to optimize disease management while maintaining physician autonomy.

Granulocyte and monocyte adsorption apheresis (GMA) is a therapeutic option for remission induction in the active ulcerative colitis (UC) patients. Effects of high processed blood volume of GMA as remission induction therapy on the long-term prognosis of UC patients have remained unclear. For this study, we investigated the relation between re-exacerbation of UC and the processed blood volume of GMA performed as induction therapy.

Data from UC patients treated using a total of 10 GMA sessions as remission induction therapy during 2012 - 2022 were retrospectively collected and analyzed. The relation between the GMA dose, processed blood volume of GMA divided by body weight, and UC re-exacerbation requiring inpatient treatment within 1 year was evaluated.

This study examined data of 72 active UC patients, with median age of 44.4 years (65% male) and median GMA dose of 34.2 mL/kg/session. Kaplan-Meier analysis showed the 1-year exacerbation-free rate was significantly higher in the higher GMA dose group than in the lower GMA dose group (P = 0.008). Cox proportional hazards regression analyses revealed a higher GMA dose as inversely associated with the re-exacerbation of UC within 1 year (hazard ratio: 0.36, 95% confidence interval: 0.17 - 0.78). Extended treatment time of GMA session beyond 60 min contributed to achieving the higher GMA dose and did not increase unexpected treatment termination because of clotting.

Greater processed blood volume of GMA per patient body weight may be associated with a lower 1-year exacerbation rate in UC patients.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and often debilitating condition requiring complex and individualized management. Over the past few decades, advancements in understanding IBD pathophysiology have led to a transformative shift in therapeutic approaches. This article provides a comprehensive overview of the evolution of IBD treatments, from early symptom-focused therapies to modern biologics, small molecule agents, and emerging treatment strategies. We discuss therapeutic goals centered on achieving clinical remission, endoscopic/mucosal healing, and enhancing patient quality of life. Additionally, we explore the rationale for the early and personalized use of biologic therapies in moderate-to-severe cases, review the current FDA-approved agents as of 2024, and highlight the advantages and limitations of these treatments. Special attention is given to the evolving role of novel oral therapies, including Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators, and future new directions. This paper aims to guide clinicians in navigating the expanding therapeutic landscape of IBD, emphasizing patient-centered decision-making and addressing ongoing challenges in achieving optimal disease control.

Acute severe ulcerative colitis (ASUC) is characterized by systemic inflammation, which may initiate an acute-phase response leading to hypercatabolism. Patients with ASUC are usually treated with high-dose steroids that may further accelerate the metabolic response and lead to hyperglycemia and insulin resistance. Nevertheless, the degree of synergy between inflammation and steroid treatment and their influence on the insulin resistance remains unknown. We aimed to measure the degree of metabolic stress including insulin resistance in patients with ASUC during admission and three weeks after discharge.

This single-center cohort study was conducted in adult patients with ASUC, defined and assessed by Truelove and Witt's criteria. Indirect calorimetry, bioelectrical impedance analysis, and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were applied at baseline and at follow-up three weeks after discharge.

Among the 22 patients admitted during the project period, 15 provided consent for participation in the study. Median C-reactive protein at inclusion was 37.6 [4; 154.7]. Both median HOMA-IR and fasting plasma glucose were markedly increased at inclusion (median 8.6 [3.8; 14.1] and 7.1 [6; 8.7], respectively), and both had decreased significantly three weeks after discharge (p=0.0036 and p=0.0039, respectively). No significant differences were observed in resting energy expenditure or anthropometric measurements from baseline to follow-up.

Patients with ASUC presented with marked insulin resistance, indicating that the days following admission and high-dose steroid treatment are particularly vulnerable. Despite improvement at three-week follow-up, patients still exhibited insulin resistance compared with relevant control groups.

ClinicalTrials.gov, identifier NCT0527183.

Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC). We aimed to assess risk factors and prognostic impact of CMV colitis in patients with moderate-to-severe UC flare. We conducted a retrospective, observational, single-center study. Consecutive adult patients hospitalized for moderate-to-severe UC from January 2020 to June 2023 were included. The primary endpoint was a diagnosis of CMV-colitis according to immunohistochemistry on tissue biopsies. The secondary endpoint was the need for colectomy within 30 days. Overall, 135 patients were included. CMV colitis was diagnosed in n = 37 (27.4%): n = 19 (51.4%) endoscopically, the remaining on surgical specimens. Of them, n = 23 (62.2%) had positive CMV-DNAemia with a median value of 1,008 cp/mL (interquartile range 318-2,980). Differences between the two groups (CMV colitis vs non-CMV) included age (60 vs 41 years, P = 0.004), Charlson Comorbidity Index (1 vs 0, P = 0.003), steroid refractoriness (86.5% vs 62.2%, P = 0.007), and positive CMV-DNAemia (62.2% vs 10.1%, P < 0.001). At multivariable analysis, steroid-refractory disease, Charlson Comorbidity Index, and CMV-DNAemia were associated with CMV colitis. Overall, n = 54 (39.7%) patients underwent colectomy, and this was significantly more common in patients with CMV colitis vs non-CMV group (54.1% vs 34.4%, P = 0.049). Kaplan-Meier showed that antiviral therapy seems to have a relevant impact on colectomy (P < 0.001). CMV-DNA blood detection is independently associated with CMV-positive refractory UC. Since CMV colitis may increase the risk of colectomy and antiviral treatment seems to reduce such risk, prospective studies are needed to confirm the role of CMV-DNA blood detection to early diagnose CMV colitis.

Cytomegalovirus (CMV) colonic reactivation worsens the prognosis of patients with active ulcerative colitis. Blood CMV-DNA reactivation is strongly associated with CMV colitis. Prompt diagnosis and treatment of CMV colitis can avoid surgery in most cases.

Severe colitis is a well-defined condition encompassing several etiologies but is most often caused by severe ulcerative colitis or Clostridioides difficile infection. Severe colitis can evolve into toxic colitis, or toxic megacolon when associated with bowel dilation and systemic manifestations, resulting in a life-threatening scenario where multidisciplinary management is often required. Medical management continues to play an important role in the initial treatment of toxic megacolon. However, timely surgical intervention can be lifesaving.

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.