Pouchitis is the most common complication after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. The authors review the role of the microbiota in both the pathogenesis of pouchitis, primarily via dysbiosis, as well as the resultant treatment strategies focused on correcting dysbiosis among patients with pouchitis. These include the role of antibiotics, probiotics, and potentially metabolomics in both treatment and risk stratification.

Common mental disorders, including anxiety and depression, are prevalent in patients with inflammatory bowel disease (IBD) and may be associated with adverse outcomes. However, whether increasing psychological co-morbidity, in combination with disease activity, exerts a cumulative effect on prognosis is uncertain.

To assess this in a longitudinal follow-up study.

We collected baseline demographic and IBD-related information, clinical activity using disease activity scores and biochemical activity using calprotectin. Patients were grouped according to the presence or absence of disease activity. Patients in remission or with active disease were subgrouped according to the presence or absence of symptoms of a common mental disorder at baseline. We recorded the occurrence of adverse outcomes over 8.1 years, comparing their occurrence across subgroups using Cox regression.

Among 717 participants with clinical activity data and 187 with clinical and biochemical activity data, rates of adverse outcomes increased with both disease activity and increasing psychological co-morbidity. Rates of flare or glucocorticosteroid prescription, escalation or death were higher with clinical activity (HR 2.89; 95% CI 1.68-4.93 and 2.52; 95% CI 1.55-4.10 and 6.97; 95% CI 2.43-20.0, respectively) or clinical and biochemical activity (HR 7.26; 95% CI 2.86-18.5, 3.62; 95% CI 1.59-8.25 and 57.3; 95% CI 7.58-433, respectively) and two common mental disorders. Rates of hospitalisation (HR 6.20; 95% CI 1.88-20.4) or hospitalisation and/or intestinal resection (HR 7.46; 95% CI 2.41-23.2) were higher with clinical and biochemical activity and two common mental disorders.

Psychological co-morbidity and active disease have a cumulative adverse impact on IBD prognosis.

Despite advances in diagnosis and pharmacotherapy, surgery remains crucial for Crohn's disease (CD). Postoperative intra-abdominal septic complications (IASC) occur in 1.2-16.7% of cases. We investigated the frequency of postoperative IASC in elective surgeries for CD and the risk factors and potential biomarkers for postoperative IASC.

We conducted a retrospective single-center cohort study of patients who underwent abdominal surgery for CD at Fukuoka University Chikushi Hospital between January 2015 and December 2023. The primary focus was the incidence of IASC within 60 days postoperatively. Patient-related variables were examined using univariate and multivariable analyses.

The analysis included 206 of 249 surgeries. Postoperative IASC occurred in 26 patients (12.6%). Univariate analysis identified history of steroid use requiring steroid coverage (p=0.002), penetrating type (p=0.020), WBC count (p=0.037), neutrophil count (0.009), C-reactive protein (CRP) (p=0.035), CRP-albumin ratio (CAR) (p=0.034), neutrophil-to-lymphocyte ratio (NLR) (p=0.002), and operation duration (p=0.010) as significant factors. Multivariable analysis identified history of steroid use requiring steroid coverage (OR=6.23, 95%CI=1.61-24.1, p=0.008), high NLR (OR=3.43, 95%CI=1.30-9.04, p=0.013), and long duration of operation (OR=2.63, 95%CI=1.01-6.88, p=0.049) as independent predictors. The optimal cutoffs for predicting IASC were an NLR of 3.98 (sensitivity, 61.5%; specificity, 77.8%) and an operation time of 173 min (sensitivity, 65.4%; specificity, 65.0%), respectively.

History of steroid use requiring steroid coverage, preoperative NLR ≧3.98, and duration of operation ≧173 min are independent risk factors for postoperative IASC in elective surgeries for CD. Recognition of high-risk patients would contribute to the decision-making process for perioperative management.

Several therapeutic advances have been achieved over the past two decades for inflammatory bowel disease (IBD). The expanding therapeutic armamentarium and the increasingly ambitious treatment targets have led to an increased use of advanced therapies and better outcomes. Nevertheless, many patients remain suboptimally treated and are at risk of disease progression, hospital admission, and surgery, even when advanced therapies are cycled, escalated, or combined. Conversely, IBD can also be characterised by an indolent disease course. Top-down and treat-to-target strategies, although beneficial in a substantial proportion of patients, might not be advantageous in patients with mild disease and might risk overtreatment. Identifying patients with mild activity and a benign disease trajectory in the long-term is important; unnecessary exposure to advanced therapies increases the risk of adverse events and increases financial costs and health-care resource utilisation. This Review details the importance of adopting clinical strategies to avoid the pitfalls of undertreating and overtreating IBD.

Epstein-Barr virus (EBV) infection of the intestinal mucosa is associated with surgical risk in ulcerative colitis (UC); however, the exact effect remains unclear.

To determine whether EBV infection can predict the need for colectomy and to develop a surgical risk predictive model.

This was a single-center retrospective study of 153 patients with moderate-to-severe UC between September 2012 and May 2023. EBV-encoded small RNA (EBER) in situ hybridization and immunohistochemistry (IHC) were used for EBV testing and assessment. Cytomegalovirus (CMV) was detected by IHC. Logistic regression analysis was conducted to identify risk factors for colectomy and develop a predictive risk model.

EBER-positivity in the intestinal mucosa was present in 40.4% (19/47) and 4.7% (5/106) of patients in the surgery and non-surgery groups, respectively, with significant differences between the groups (P < 0.01, odds ratio = 13.707). The result of multivariate logistic regression revealed that age, EBV infection in the colonic mucosa, CMV infection in the colonic mucosa, and treatment with three or more immunosuppressive agents before admission were significant independent predictors of colectomy. A nomogram incorporating these variables demonstrated good discriminative ability, and exhibited good calibration and clinical utility. IHC showed that EBV-infected cells mainly included B and T lymphocytes in patients with high EBER concentrations.

EBV infection of the intestinal mucosa is a significant independent risk factor for colectomy in patients with moderate-to-severe UC. The nomogram model, which includes EBV infection, effectively predicts colectomy risk.

Fecal calprotectin (Fcal) and intestinal ultrasonography (IUS) could be used as noninvasive tools to monitor mucosal and transmural healing, respectively, in Crohn's disease (CD). We assessed the agreement between Fcal and IUS to detect active CD and investigated their complementary to predict long-term CD outcomes.

In this prospective study, we consecutively included CD patients with concomitant IUS and Fcal testing within 7 days. Patients were divided into 4 groups: Transmural healing (TH; both normal), IUS healing (Fcal > 100 µg/g but normal IUS), biochemical remission reflecting mucosal healing (MH; Fcal < 100 µg/g but abnormal IUS), and no healing (abnormal Fcal and IUS). The primary endpoint was active CD. The secondary endpoints were time to bowel damage progression, time to relapse-related drug discontinuation, and patients' acceptability (10-points acceptability numerical scale).

Among the included 112 patients, 44.6% (50/112), 12.5% (14/112),16.1% (18/112), and 26.8% (30/122) achieved TH, IUS healing, biochemical remission, and no healing, respectively. The agreement between IUS and Fcal to detect an active CD was poor (71.4%, κ-coefficient = 0.41 ± 0.09). Transmural healing was associated with a reduced risk of bowel damage progression compared to no healing (P < .0001) contrary to IUS healing (P = .15) or biochemical remission (P = .84). Transmural healing was associated with a lower risk of relapse-related drug discontinuation than MH (hazard ratio [HR] = 0.09 [0.02-0.45], P = .003), IUS healing (HR = 0.10 [0.02-0.60], P = .001), or no healing (HR = 0.09 [0.018-0.04], P = .002). IUS was better accepted than Fcal testing (9.6 ± 0.8 vs 7.9 ± 2.3; P < .0001, 10-points range-acceptability numerical scale).

Transmural healing, evaluated by the combination of noninvasive and well-accepted tools such as Fcal and IUS, is associated with improved long-term outcomes and could be used to monitor patients with CD in daily practice.

Perianal fistulising Crohn's disease (PFCD) is a debilitating phenotype of Crohn's disease, with a lifetime incidence of 20-30% in people living with the dieases. Symptoms include perianal pain, perianal discharge and faecal incontinence, with repercussions for a patient's physical and mental health, psychosocial wellbeing and productivity. PFCD is challenging to treat, with existing therapeutic options achieving modest fistula remission rates only. While research initiatives are under way to characterise PFCD pathogenesis and optimal treatment approaches, the focus should be on early diagnosis and prompt management. This can be achieved with patient education, effective co-ordination of care within the multidisciplinary team and an accessible inflammatory bowel disease (IBD) service. IBD specialist nurses may be the first health professionals to encounter a patient with a new diagnosis of PFCD or its complications. This review article summarises the existing evidence relating to clinical aspects of PFCD from a multiprofessional perspective and discusses the role of a dedicated IBD surgical link nurse in PFCD management in a tertiary centre setting.

Pouchitis, defined as inflammation of the ileal pouch, is the most common complication following restorative proctocolectomy for refractory ulcerative colitis. Antibiotics remain the first line of therapy for pouchitis, but the majority of patients develop subsequent episodes and some are refractory to antibiotic therapy. This highlights the need for more effective treatment options and points to a more complex pathophysiology beyond the role of th pouch microbiome, similar to what is seen in inflammatory bowel disease. In this review, we outline the putative mechanisms of pouchitis, including genetic predisposition, microbiome alterations, dysfunction of the intestinal barrier and the immune system and review the available animal models of pouchitis. In addition, we introduce the concept of pouchitis as a possible transmural disease and discuss the potential role of non-immune cells, including stromal cells, in perpetuating inflammation and intestinal barrier dysfunction. We discuss future directions, implications for novel therapies and propose novel multicellular disease models that can better capture the complexity of pouchitis pathogenesis.

Despite advances in medical therapies for the treatment of Crohn's disease (CD), 20-30% of patients fail to respond to these therapies (i.e. refractory CD). Medically refractory CD leads to significant disability increasing morbidity and mortality. To prevent the disability of refractory CD, hematopoietic stem cell transplantation (SCT) has emerged as a therapeutic strategy.

Autologous (auto-SCT) and allogeneic SCT (allo-SCT) have been explored in clinical trials for refractory CD patients. We will review the stem cell transplant process, how each part of stem cell transplantation affects clinical efficacy and safety, and how specific clinical trials advanced our understanding of the role of stem cell transplant in the treatment of refractory CD.

As multiple clinical trials using the same auto-SCT protocol demonstrated auto-SCT as clinically efficacious for refractory CD it supports that this treatment may be adopted as standard of care for select patients with refractory CD. To establish auto-SCT as a standard therapy will require the creation of international registries to track long-term SCT outcomes and translational studies to refine SCT protocols for CD patients as a cellular therapy that truly restores healthy intestinal immune cell populations from hematopoietic stem cells.

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD.

With nearly 60 million Americans aged 65 and older, gastrointestinal (GI) conditions are a leading cause of healthcare utilization in this population. Despite this, older adults remain underrepresented in GI clinical trials and research, limiting evidence-based care. This review highlights three pivotal studies addressing this gap: (1) proton pump inhibitors, which are commonly used to treat gastroesophageal reflux disease, are not associated with the later development of dementia; (2) undertreatment of chronic inflammation among older adults with inflammatory bowel disease is associated with a higher rate of adverse events compared to treatment with anti-TNF therapy, a biologic agent; (3) the majority (85%) of surveillance colonoscopies among older adults with a life expectancy of ≥ 10 years did not yield colorectal cancer, advanced dysplasia, or ≥ 3 polyps.

Over 10% of patients with Crohn's disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn's disease patients with permanent ileostomy.

MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn's disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence.

Thirty cohort studies including 2055 Crohn's patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3-33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn's disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous.

There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn's disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.

The majority of patients with Crohn's disease, despite an ever-increasing number of advanced therapies, require abdominal surgery during their lifetime. In this review article, the authors provide a comprehensive overview of abdominal surgery for Crohn's disease, with an evidence-based focus on surgery for upper gastrointestinal Crohn's disease, bowel-preserving surgery with strictureplasties, selection of ileocolic anastomotic technique for terminal ileal Crohn's disease, extended resections and proctectomy for Crohn's proctocolitis, intentional ileoanal pouch for Crohn's disease, and several "hot topics" including early surgery for ileocolic Crohn's disease, and surgical approaches that target the mesentery including the Kono-S anastomosis and extended mesenteric excision.

To assess the real-life, long-term effectiveness and safety of tofacitinib in a large cohort of patients with refractory or difficult-to-treat ulcerative colitis (UC).

This multicenter, retrospective, observational cohort study included patients with moderately to severely active UC who received tofacitinib for at least 8 weeks. Clinical remission and response, endoscopic response and remission, biochemical response and remission, steroid-free clinical remission, primary and secondary loss of response, drug discontinuation, the need for dose optimization, the need for colectomy, and adverse events were evaluated over up to 30 months.

We included 127 patients with UC, with a mean age of 40.3 ± 14.2 years; 58.2% were male, 75.6% had pancolitis, and 79.5% had previously failed at least one biological therapy, predominantly anti-TNF agents (70.1%). Clinical remission was observed in 31.5% of patients at weeks 12-16, 46.5% at 26 ± 4 weeks, and 37.0% at 1 year. Steroid-free clinical remission was achieved in 28.6%, 44.8%, and 37.1% of patients at the same time points, respectively. Biochemical remission was achieved in 33.6% of patients at 26 ± 4 weeks and 29.3% at 1 year. Endoscopic response and endoscopic remission within 1 year were observed in 46.0% and 15.3% of patients, respectively. Ten patients (7.9%) required colectomy, and 13 patients (10.2%) required hospitalization, all of whom had been previously exposed to biologics. The colectomy rate was significantly greater in patients with serum albumin levels ≤ 3.5 g/dL (21.4% vs. 4.1%, p = 0.013).

In this large, long-term real-world study involving patients with predominantly biologically refractory UC, tofacitinib effectively induced clinical remission and endoscopic improvement and prevented colectomy for more than 30 months, with a favorable safety profile. Notably, baseline hypoalbuminemia was associated with higher colectomy rates.

The impact of prophylactic medication following ileocecal resection (ICR) for Crohn's disease (CD) merits further elucidation. Prophylactic medication following ileocecal resection (ICR) is recommended in patients with Crohn's disease (CD), particularly in patients at increased risk of recurrence, but the impact on long-term outcomes needs to be further elucidated.

To evaluate the effect of postoperative prophylactic medication on long-term prognosis.

A retrospective cohort study was performed in patients with CD who underwent primary ICR between 2000-2020 in the Netherlands. Patients were divided into two groups: postoperative prophylactic medication [< 12 weeks following ICR] versus no postoperative prophylactic medication. Outcomes were surgical recurrence [re-resection for CD], severe endoscopic recurrence [modified Rutgeerts score (mRS) ≥ i3] and endoscopic or radiologic recurrence [mRS ≥ i2b or radiologic recurrence]. Inverse probability of treatment weighting [IPTW] method was used to adjust for confounding and selection bias. Survival and association between postoperative prophylactic medication and outcomes were assessed with Kaplan-Meier analyses and Cox proportional hazard models.

807 patients underwent ICR (median follow-up 5.0 years); 36% received postoperative prophylactic medication. Surgical, severe endoscopic and endoscopic or radiologic recurrence rates were significantly lower in those who received prophylactic medication (p = 0.01; p < 0.01; p < 0.01). IPTW analysis showed a lower risk of severe endoscopic and endoscopic or radiologic recurrence in patients treated with postoperative prophylactic medication (aOR 0.64; 95% CI 0.43-0.97; aOR 0.65; 95% CI 0.47-0.91), which also was identified as a protective factor for severe endoscopic (aHR 0.5; 95% CI 0.4-0.6) and endoscopic or radiologic recurrence (aHR 0.6, 95% CI 0.5-0.7) in multivariable analysis after correction for confounding factors. A comparable protective effect of postoperative prophylactic medication was sustained in patients who underwent ileocolonoscopy <1 year postoperatively and who underwent surgery on or after 2010.

Prophylactic medication following primary ICR significantly reduces long-term recurrence rates in CD and was identified as a protective factor for severe endoscopic and endoscopic or radiologic recurrence.

Many pediatric inflammatory bowel disease (IBD) patients require surgical intervention during their lifetime. Poor nutrition status correlates with adverse surgical outcomes in the adult population. A paucity of data exists on the association of preoperative nutrition status and postoperative outcomes in the pediatric population. We sought to determine the correlation between nutrition status and perioperative outcomes following a planned operation.

A retrospective review was conducted at a tertiary children's hospital from January 2010-December 2022 for all children ≤18 years old, with a diagnosis of IBD, undergoing elective surgery, with preoperative nutrition data. Patients were grouped into none/mild malnutrition and moderate/severe malnutrition based on BMI Z-scores or two-weight differences, and outcomes compared: postoperative complications, hospital length of stay (LOS), and unplanned reoperation. Sarcopenic measures based on cross-sectional imaging were collected.

Ninety-three planned surgical admissions were identified; 70 in the none/mild malnutrition group and 23 in the moderate/severe malnutrition group. There were no significant differences in post-operative complication rates (38.1 % moderate/severe vs. 22.4 % none/mild, p = 0.18). The moderate/severe malnutrition group had a longer LOS (8.6 ± 4.8 days vs. 5.7 ± 2.6 days; p = 0.01) and a higher risk of unplanned reoperation (n = 8, 34.8 % vs. n = 5, 7.1 %, p = 0.03). Psoas index was significantly higher between none/mild and moderate/severe malnutrition groups (6.5 ± 1.9 vs 4.6 ± 2.0, p = 0.01).

Pediatric IBD patients undergoing elective surgery with moderate/severe malnutrition are at increased risk of a longer hospital LOS and unplanned reoperation. Radiographic sarcopenic measures correlate with malnutrition status based on BMI Z-scores and warrant further investigation for predicting post-operative outcomes in this population.

IV.

Recurrence after surgically induced remission in Crohn's disease remains a topic of research and debate with significant clinical implications for overall quality of life and intestinal and defecatory functions. While the surgeon continues to play a critical role in surgical prophylaxis of recurrence, optimal results will only be obtained in the setting of a true multidisciplinary team approach, following the principles of "the right surgery, on the right patient, at the right time, performed by the right surgeon, supported by the right team." The centerpiece of surgical prophylaxis is the intestinal anastomosis. The ideal anastomosis after resection for Crohn's disease should be safe and reliable, as postoperative septic complications have been shown to increase the risk of recurrence; result in a wide lumen and a configuration that would not impede enteric flow; exclude or excise the mesentery, a known culprit in primary and recurrent disease; and preserve vascularization and innervation. This article will review the evidence supporting the above-mentioned surgical principles and the long-term results of the different anastomotic configurations.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic gastrointestinal condition with a multifactorial etiology. It significantly impacts patients' quality of life, particularly, in rural areas where access to specialized care is limited. Challenges such as increased travel costs, social isolation, and restricted healthcare access are recognized, but their specific impact on rural Italian patients remains underexplored. This study aims to fill this gap. Using Cohen's hermeneutic phenomenological approach, in-depth interviews were conducted with 17 IBD patients from rural areas. Thematic analysis identified key patterns and themes. Two main themes emerged: "challenges of rural living," including economic concerns and social isolation, and "communication that bridges distances." Rural IBD patients face unique challenges extending beyond disease management, with economic hardship and social isolation being prominent. These findings highlight the need for tailored interventions to bridge healthcare gaps and improve the quality of life for rural patients, offering novel insights into their lived experiences in Italy.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterised by episodes of symptoms including rectal bleeding, increased stool frequency and abdominal pain, impacting quality of life significantly. Conventional treatments often come with potential side effects and may not be sufficient. Acupuncture is increasingly recognised for its potential benefits in UC. This study aims to assess the efficacy and safety of acupuncture for symptom relief in mild to moderate UC.

This single-centre, parallel-arm, randomised, sham-controlled, the two-step acupuncture (TSA)-UC trial, will involve 64 adults with mild to moderate UC, randomly assigned in a 1:1 ratio to either the acupuncture or sham acupuncture group. Participants will receive 20 sessions of two-step acupuncture or sham acupuncture therapy over 8 weeks. Blinding will be applied to participants, outcome assessors and statisticians. The primary outcome measure is the change in Patient-Reported Outcome 2 (PRO2) from baseline at week 8. Secondary outcomes include changes from baseline in the following scales: PRO2 at other time points, weekly average Numeric Rating Scale (NRS) for bowel urgency, weekly average NRS for abdominal pain (both associated and not associated with bowel movement), the 32-item Inflammatory Bowel Disease Questionnaire, Work Productivity and Activity Impairment Questionnaire-IBD, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. The Patient Global Impression of Change will also be assessed. Long-term effects of acupuncture will be explored. Adverse events and additional treatments will be monitored throughout the study. The modified intention-to-treat population including participants who complete baseline assessments and receive at least one treatment session will be analysed.

The study has received ethical approval from the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (2024-190-KY). The results will be published in a peer-reviewed medical journal.

NCT06615765.

Refractory inflammatory bowel disease (IBD) remains challenging despite the availability of various biologics. Advanced combination therapy (ACT) with biologics and Upadacitinib (UPA), a rapid-onset oral selective Janus kinase inhibitor, has shown promise in managing refractory IBD. However, its use in Asia has not been explored. This study aims to fill that gap by providing data from Taiwan.

This retrospective study included refractory IBD patients who received ACT with biologics and UPA, followed up at the Chang Gung Inflammatory Bowel Disease Center from July 2020 to August 2024. Patients were assessed for clinical response and remission at weeks 4, 12, and 24. Safety profiles were monitored throughout the follow-up period to evaluate the risk of adverse events.

Sixteen refractory IBD patients were enrolled. The median disease duration was 4.5 years [IQR 2.25-9.50]. The most common regimen was Ustekinumab plus UPA (63%). Clinical response rates at weeks 4, 12, and 24 were 88%, 83%, and 100%, respectively, while remission rates were 31%, 50%, and 80%. One patient (6.25%) experienced a minor adverse event (acne), with no major events like herpes zoster reactivation or major cardiac complications.

This is the first study in Asia to demonstrate that UPA-based ACT is both effective and safe in treating refractory IBD. However, the limitations of this retrospective, single-center study with a relatively small sample size highlight the need for future larger-scale, multi-center prospective studies to confirm these findings, identify predictors of treatment response, and evaluate long-term outcomes.

Objectives: This bibliometric analysis investigates recent research trends in biologics and small molecules for treating inflammatory bowel disease (IBD) based on literature from the past decade. Methods: This cross-sectional study involved analyzing data retrieved from the Web of Science Core Collection (WoSCC) database to examine the evolution and thematic trends of biological agents and small-molecular drugs for IBD conducted between 1 January 2014, and 20 September 2024. VOSviewer software was utilized to assess co-authorship, co-occurrence, co-citation, and network visualization, followed by a further discussion on significant sub-themes. Results: From 2014 to 20 September 2024, the annual number of global publications increased by 23%, reflecting an acceleration in research activity. The journal "Inflammatory Bowel Diseases" published the highest number of manuscripts (579 publications) and garnered the most citations (13,632 citations), followed by the "Journal of Crohn's & Colitis" (480 publications) and "Alimentary Pharmacology & Therapeutics" (250 publications). The United States led in productivity with 1943 publications and 66,320 citations, with UC San Diego (291) and authors Sandborn and Vermeire (180) topping the list. The co-occurrence cluster analysis of the top 100 keywords resulted in the formation of six distinct clusters: Disease Mechanisms, Drug Development, Surgical Interventions, Therapeutic Drug Monitoring (TDM), Immunological Targets, and Emerging Therapies. Burst terms (TNF-α inhibitors, JAK inhibitors, and trough-level optimization) highlight trends toward personalized biologics and small-molecule regimens. Conclusions: The bibliometric analysis indicates that IBD therapeutic research and clinical applications focus on biologics and small molecules, with research trends leaning toward precise therapy conversion or the combination in non-responders. Future work will assess monotherapy, the combination, and conversion therapies and investigate new drugs targeting inflammatory pathways.

Vedolizumab (VDZ) and infliximab (IFX) are first-line therapies for moderate-to-severe ulcerative colitis (UC). Despite their widespread use, there are no direct comparative studies, and real-world data, particularly in Latin America, are limited. This study compared the effectiveness and safety of VDZ and IFX in biologic-naïve UC patients.

This retrospective cohort study included patients with moderate-to-severe UC (Mayo score 6-12, endoscopic sub-score ≥2) treated with VDZ or IFX. Primary endpoints were clinical remission (partial Mayo score ≤2), endoscopic remission (Mayo sub-score=0), and steroid-free clinical remission at week 52. Secondary endpoints included clinical response, endoscopic response, biological therapy optimization, adverse events (AEs), hospitalizations, and biochemical remission at week 52. Propensity score adjustment (1/PS) was used to adjust for potential confounders.

A total of 297 UC patients (156 IFX, 141 VDZ) were analyzed. Clinical remission at week 52 was 82.3% for VDZ and 77.6% for IFX (p=0.11), while endoscopic remission was higher in VDZ patients (47.4% vs. 33.1%, p=0.03). Steroid-free clinical remission rates were similar between groups (p=0.98). Endoscopic response at week 52 favored VDZ (78.4% vs. 62.7%, p<0.001), and VDZ had higher treatment persistence (80.8% vs. 61.8%, p<0.001). AEs and hospitalizations were more frequent in IFX patients (p<0.001).

Both VDZ and IFX are effective in biologic-naïve UC patients, however VDZ demonstrated superior endoscopic outcomes, higher treatment persistence, and a better safety profile, supporting its use as a first-line therapy.

Pouchitis remains the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (IPAA). Despite the burden of pouchitis, our ability to recognize the patients at greatest risk for pouchitis and to offer early intervention for the prevention or early treatment is limited.

In this review, we will discuss the diagnostic categories of pouchitis, as well as the common approaches to treatment. We will then discuss gaps in research and clinical care. These include opportunities to improve our understanding of the risk factors associated with the development of pouchitis as well as the role that primary and secondary prevention may play in the management of patients after IPAA to prevent pouchitis. We will then discuss future research goals to decrease the burden of pouchitis.

Although the burden of pouchitis is well recognized, we have an opportunity to improve our methods of risk stratification to offer early intervention to those patients at the greatest risk for developing pouchitis. Understanding which preventive therapies, in which populations, and under which treatment settings offer the most benefit will be critical issues to address in the near future to improve care of patients after IPAA for UC.

Our objective was to compare the efficacy of novel biologics (such as vedolizumab and ustekinumab), anti-tumor necrosis factor (anti-TNF) agents, and immunomodulators (IMMs) in preventing postoperative recurrence (POR) of Crohn's disease (CD).

We searched the PubMed, Embase, and the Cochrane Library databases up to December 2023 to identify placebo-controlled, no-treatment comparison, or positive-controlled studies for the prevention of POR in CD. Endoscopic recurrence and clinical recurrence were the primary and secondary endpoints for the efficacy assessment. We conducted traditional direct and Bayesian network meta-analyses to evaluate the preventive effects of selected drugs. Additionally, we ranked interventions based on their scores under the Surface Under the Cumulative Ranking curve (SUCRA).

A total of 17 studies involving 2786 patients were included. In the direct meta-analysis, anti-TNFs, vedolizumab, and IMMs showed greater efficacy in preventing endoscopic POR, compared with controls (placebo or no treatment). In preventing clinical POR, anti-TNFs and IMMs outperformed the controls. The network meta-analysis revealed that the risk of endoscopic POR was considerably lower in patients receiving anti-TNFs, vedolizumab, and ustekinumab compared with controls. Regarding the reduction of clinical POR, only anti-TNFs showed significant efficacy compared with controls. Vedolizumab and anti-TNFs were ranked as the most effective strategies in preventing endoscopic and clinical recurrence, respectively.

According to direct and network meta-analysis, in CD patients after surgical resection, novel biologics, especially vedolizumab, were quite effective in decreasing the risk of endoscopic POR, whereas anti-TNFs appeared to perform best in reducing the risk of clinical POR.

Patients undergoing Crohn's disease (CD) surgery may develop a higher rate of postoperative complications (POC) than other patients.

The aim of this study was to investigate factors determining POC in patients with CD undergoing urgent laparotomy.

This is a retrospective cohort study conducted on adult patients undergoing urgent laparotomy for CD. Clinical and surgical variables, medication history, American Society of Anesthesiologists classification, and POC were investigated. Data collection and management were carried out using the REDCap software (REDCap electronic data capture tools) hosted at the hospital institution. For statistical analysis, the χ2 (or Fisher's exact) test, Student's t-test, Mann-Whitney test, and simple and multiple multilevel logistic regression analyses were used.

There was an association regarding the history of adalimumab use (p=0.04, OR 2.8, 95%CI 1.03-7.65), previous use of prednisone (p<0.01, OR 2.03, 95%CI 2.00-2.05), urgent surgery indications (p<0.01, OR=4.32, 95% CI=1.58-11.82), mechanical anastomosis (p=0.02, OR=0.22, 95%CI 0.06-0.80), unexpected intraoperative findings (p=0.02, OR 10.46, 95%CI 1.50-72.99), length of hospital stay greater than 10 days (p<0.01, OR 16.86, 95%CI 2.99-94.96), unplanned intensive care unit (ICU) admission (p=0.01, OR 15.06, 95%CI 1.96-115.70), and planned ICU admission (p<0.01, OR 18.46, 95%CI 3.60-94.51). On multivariate analysis, there was an association between the indication of urgent surgery (or emergency) (p=0.01, OR 4.38, 95%CI 1.43-13.37) and unexpected intraoperative findings (p=0.03, OR 8.11, 95%CI 1.21-54.50).

Unexpected changes and urgent surgical indications are considered risk factors for POC in patients with CD.

The impact of diverting ileostomy in adults with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) is unclear. This study uses a novel approach with population-level data to identify patients with diverting ileostomy at the time of IPAA and determine the impact of diverting ileostomy on postoperative outcomes.

Using the International Business Machines (IBM) MarketScan® database, adults (18-64 years old) with a diagnosis of UC who underwent IPAA between 2000 and 2019 were examined. Patients were assigned to the diverting ileostomy (DI) cohort or no-DI cohort based on the presence of an ostomy closure code in the 1-year following their IPAA. Rates of ileostomy formation and readmissions were quantified and outcomes between cohorts compared.

There were 540 patients in the no-DI and 2494 in the DI cohort. There were regional differences in the rate of ostomy creation, but the overall rate of ostomy creation remained stable across years. Patients with no-DI vs DI had a longer index length of stay (LOS) (7 vs 6 days, P = .001). Adverse postoperative outcomes did not differ between cohorts. Diversion did not independently affect the likelihood of a 30-day readmission, and since 2000, readmission rates have declined for all IPAA patients.

This is the first study to capture population-level data on the effect of diversion at the time of IPAA for adult UC patients. This study demonstrates that the rate of fecal diversion at the time of IPAA has remained stable over time, but readmission rates have declined.

The ulcerative colitis intestinal ultrasound (UC-IUS) index (UII) has been reported as a sonographic scoring system correlating with the Mayo endoscopic subscore (MES). Endoscopic improvement (EI) of UC (MES ≤ 1) is a crucial therapeutic target in clinical practice. However, the cutoff value for estimating EI using the UII has not been established.

We established test and validation cohorts comprising patients with UC undergoing IUS and endoscopy within a 15-day interval at our institution. IUS findings (bowel wall thickness, bowel blood flow, bowel wall structure, haustrations, and inflammatory fat) and endoscopic activity (MES) of each colon segment (ascending, transverse, descending, and sigmoid colon) were assessed.

In the test cohort (74 segments), UII was correlated with MES (r = 0.645, p < 0.0001). The median UII was 1.0 and 6.0 among participants with MES ≤ 1 and MES ≥ 2, respectively. A UII of 2 was identified as the threshold for estimating MES ≤ 1 with receiver operating characteristic analysis. In the validation cohort (122 segments), UII was correlated with MES (r = 0.675, p < 0.0001) and the estimation ability of UII ≤ 2 for EI had a positive predictive value of 85.4% and negative predictive value of 79.0%. This estimation ability of UII for EI was numerically lower but not statistically different from the previously reported Milan Ultrasound Criteria and Kyorin Ultrasound Criterion for UC.

UII ≤ 2 can be a simple, feasible criterion for estimating EI. Correlation with MES is an advantage of the UII compared with other criteria. Proper use of various sonographic criteria is important.

Three Janus kinase (JAK) inhibitors are approved for ulcerative colitis (UC) in Japan.

To compare the real-world efficacy and safety of these three JAK inhibitors in UC.

This was a multicentre, retrospective study of patients with UC started on JAK inhibitors. The primary outcome was clinical remission at 10, 26 and 58 weeks, and at the most recent follow-up. To compare the efficacy and safety among the JAK inhibitors, we created three matched cohorts (upadacitinib vs. filgotinib, tofacitinib vs. filgotinib and upadacitinib vs. tofacitinib) using propensity score matching.

We identified 228 upadacitinib-treated patients (median follow-up 49 weeks; IQR 25-72), 215 filgotinib-treated patients (follow-up 56 weeks; IQR 17-82) and 159 tofacitinib-treated patients (follow-up 112 weeks; IQR 10-258). Clinical remission rates for upadacitinib, filgotinib and tofacitinib at the most recent follow-up were 72.8%, 50.6% and 45.8%, respectively. Over 70% of the patients previously treated with other biologics or JAK inhibitors achieved clinical remission with upadacitinib. On multivariate analysis, the number of previous advanced therapies was inversely associated with the efficacy of filgotinib and tofacitinib. Comparative analysis showed that upadacitinib-treated patients had higher efficacy and lower risk of discontinuation than patients treated with other JAK inhibitors. However, upadacitinib had a significant risk of acne.

Considering the particularly high efficacy of upadacitinib, even in patients with refractory UC, filgotinib or tofacitinib may be considered as an upfront JAK inhibitor before using upadacitinib.

Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.

Total proctocolectomy (TPC) is the standard of care for patients with ulcerative colitis (UC) and dysplasia not amenable to endoscopic management. However, the risks of an extensive resection may outweigh the benefits in high-risk surgical patients. Therefore, we performed a systematic review and meta-analysis to assess postoperative outcomes between segmental colectomy (SEG) versus TPC in patients with UC.

Global databases were searched from inception until August 2022 for comparative studies reporting the postoperative outcomes of patients with UC undergoing SEG versus TPC. The primary outcomes were subsequent neoplasia development and overall survival. Odds ratios (ORs), hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The Newcastle-Ottawa Scale and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for quality-of-evidence assessment.

Eight retrospective studies comprising 4856 patients were included. Overall, 1620 (33%) patients underwent SEG. SEG patients were older, had more comorbidities and mostly underwent right colectomy (40%) and sigmoidectomy (16%). Most studies included UC patients and concomitant colorectal cancer. Reoperation and Clavien-Dindo III-IV odds were equivalent (OR 3.17; 95% CI 0.12, 81.25; I2 66%; OR 0.79; 95% CI 0.48, 1.31; I2 74%). There was no difference in neoplasia development (OR 5.05, 95% CI 0.37, 68.66; I2 61%) nor in overall survival (HR 1.20, 95% CI 0.73, 1.97; I2 61%). The risk of bias was high in all included studies and the quality of evidence was low.

Low-quality evidence failed to demonstrate any discernible differences in the postoperative outcomes between SEG and TPC. However, given the limited granularity of the analysed data and the high likelihood of imprecise results, we cannot assert that SEG and TPC are equivalent. Furthermore, there was a suggestion of an elevated risk of neoplasia development and inferior overall survival in the SEG group.

A significant proportion of patients with Crohn's disease or ulcerative colitis will ultimately necessitate surgical interventions, despite advances in diagnosis, medical therapy, and endoscopic interventions. These surgeries lead to substantial alterations in bowel anatomy. The present review aims to emphasize the key role of conducting a comprehensive endoscopic evaluation of both anatomic landmarks and endoscopic features for accurate clinical interpretation, thereby impacting decisions regarding medical or endoscopic interventions.

Biological therapy has transformed the natural course of inflammatory bowel disease, but there are still controversies regarding its potential to reduce surgical rates for Crohn's disease (CD). This study, conducted with the support of the Brazilian National Healthcare System, aimed to analyze temporal trends in surgery and hospitalization rates among patients with CD and to correlate these data with the dispensing of azathioprine (AZA), infliximab (IFX), and adalimumab (ADA).

This retrospective observational study used data from the National Public Healthcare Department of Informatics through the TT Disease Explorer® platform from 2012 to 2022. Demographic data, medications used, and the prevalence of surgical procedures and hospitalizations associated with the International Classification of Diseases codes for CD were analyzed. Annual average percent changes (AAPCs) were calculated to assess temporal trends.

Between 2012 and 2022, there was a significant increase of 288.07% in the diagnoses of CD, rising from 27 551 to 106 917 cases. Concurrently, there was an increase in the absolute number of patients treated with AZA, IFX, and ADA, with increasing rates of 65.79%, 251.09%, and 242.48%, respectively. However, the proportion of patients receiving AZA per CD patients decreased by 57.28%, from 44.79% to 19.13% (AAPC = -7.94%, 95% CI, -8.05 to -7.83; P < .001). The use of IFX remained relatively stable, with a slight change from 13.82% to 12.50% (AAPC = 0.01%, 95% CI, -0.20 to 0.22; P = .935), while the use of ADA decreased by 11.75%, from 11.65% to 10.28% (AAPC = -1.74%, 95% CI, -2.48 to -1.82; P < .001). The absolute number of hospitalizations related to CD increased by 57.71%. Despite the rise in the number of cases and the greater availability of biological treatments, the proportion of hospitalized patients decreased by 59.29%, from 6.19% to 2.52% (AAPC = -7.04%, 95% CI, -7.42 to -6.66; P < .001). Similarly, the proportion of surgical procedures relative to the total number of cases decreased by 55.08%, from 1.09% to 0.49% (AAPC = -5.73%, 95% CI, -6.68 to -4.77; P < .001).

Despite the cumulative increase in the prevalence of CD cases in the country and the absolute increase in the dispensing of biologics, the proportion of hospitalizations and surgical procedures among CD patients treated in the public health system in Brazil decreased.

Pouchitis and Crohn's-like disease of the pouch (CLDP) are common in patients who undergo ileal pouch anal anastomosis for ulcerative colitis. We conducted separate systematic reviews to evaluate the effectiveness of available interventions to prevent and treat pouchitis and CLDP.

Through systematic literature reviews, we identified studies that evaluated the effectiveness of probiotics, antibiotics, 5-aminosalicylates, nonsystemic oral corticosteroids, and advanced therapies for prevention and treatment of pouchitis and CLDP for meta-analysis. Primary outcomes were occurrence of pouchitis for pouchitis prevention and clinical response for pouchitis and CLDP treatment. We estimated the relative effectiveness of these interventions using the existing placebo response rates or hypothetical spontaneous improvement rates derived from clinical trials of pouchitis, ulcerative colitis, and Crohn's disease.

Probiotics were effective for primary (relative risk [RR] 0.18; 95% confidence interval [CI] 0.05-0.62) and secondary prevention (RR 0.17; 95% CI 0.09-0.34) of pouchitis. Antibiotics were effective for treatment of acute and chronic pouchitis (12 cohorts; RR 1.67; 95% CI 1.34-2.01; response rate 65%; 95% CI 52-75) with ciprofloxacin and metronidazole-based regimens being more effective than rifaximin. Advanced therapies were effective for treatment of chronic antibiotic-refractory pouchitis (31 cohorts; RR 1.71; 95% CI 1.28-2.56; response rate 50%; 95% CI 43-57) and CLDP (10 cohorts; RR 2.49; 95% CI 1.87-3.73; response rate 74%; 95% CI 68-79) without significant difference between classes.

Multiple medical interventions are effective for prevention and treatment of pouchitis and CLDP. Given the overall low quality of data, further research is needed to confirm these findings.

Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease.

REPREVIO was a double-blind, randomised, placebo-controlled trial conducted at 13 academic or teaching hospitals in France, Italy, the Netherlands, and Spain. Eligible participants were adult patients aged 18 years or older with Crohn's disease who underwent ileocolonic resection and had one or more risk factors for recurrence. Patients were randomly assigned within 4 weeks of surgery (1:1 ratio) to receive intravenous vedolizumab (300 mg) or placebo at weeks 0, 8, 16, and 24. Randomisation was performed centrally with a computer-generated validated variable block model and patients were stratified according to disease behaviour (fibrostenotic vs inflammatory or perforating). Ileocolonoscopy was performed at week 26 and videorecorded. Endoscopic recurrence was centrally assessed with the modified Rutgeerts score, a categorial score ranging from i0 to i4. The primary endpoint was the distribution of modified Rutgeerts scores between treatment groups at week 26, analysed by non-parametric methods. The first-ranked secondary endpoint was the proportion of patients with severe endoscopic recurrence of Crohn's disease at week 26 (modified Rutgeerts score ≥i2b). Primary and safety analyses included all patients who underwent randomisation and received at least one dose of study drug. The trial is registered with the EU Clinical Trial Register (EudraCT; 2015-000555-24).

Between May 16, 2017, and April 8, 2022, 84 patients were randomly assigned to treatment, of whom four did not receive study treatment, leaving 43 patients in the vedolizumab group and 37 in the placebo group. At week 26, the probability of a lower modified Rutgeerts score with vedolizumab versus placebo was 77·8% (95% CI 66·4 to 86·3; p<0·0001). Severe endoscopic recurrence was observed in ten (23·3%) of 43 patients in the vedolizumab group versus 23 (62·2%) of 37 patients in the placebo group (difference -38·9% [95% CI -56·0 to -17·3]; p=0·0004). Serious adverse events occurred in three (7·0%) of 43 patients who received vedolizumab (bilateral tubo-ovarian abscesses, thrombosed haemorrhoids, and pancreatic adenocarcinoma) and in two (5·4%) of 37 patients who received placebo (intestinal perforation related to Crohn's disease and severe abdominal pain).

Vedolizumab treatment within 4 weeks of ileocolonic resection was more likely to prevent endoscopic Crohn's disease recurrence than placebo, making this an attractive option for postoperative management in patients with risk factors for recurrence. Larger studies with longer follow-up would be desirable.

Takeda Nederland.

Fecal calprotectin (FC) is a promising biomarker for assessing ulcerative colitis (UC) endoscopic activity. However, the optimal FC cutoff to identify each Mayo endoscopic subscore (MES) remains inconclusive.

The electronic medical records of 177 adult UC patients evaluated at Mayo Clinic Rochester from January 2017 to March 2023 were retrospectively reviewed, obtaining clinical data and US-based Werfen Diagnostics FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES.

The median interval between FC collection and endoscopy was 2 days. Fecal calprotectin showed strong positive correlations with MES (Spearman's r = 0.709; P < .01) and other clinical parameters. Fecal calprotectin cutoff of 60 mcg/g effectively distinguished MES 0 from MES 1-3 (sensitivity, 0.78; specificity, 0.97; area under the receiver operating characteristic curve [AUC], 0.901) and predicted clinical remission (Total Mayo Score ≤2 and no subscore >1; sensitivity, 0.83; specificity, 0.98; AUC, 0.921). Fecal calprotectin cutoff of 110 mcg/g effectively differentiated MES 0-1 from MES 2-3 (sensitivity, 0.86; specificity, 0.87; AUC, 0.915), while a cutoff of 310 mcg/g distinguished MES 0-2 from MES 3 (sensitivity, 0.80; specificity, 0.76; AUC, 0.820).

This study supports the reliability and applicability of FC as a valuable marker of endoscopic inflammation, particularly in distinguishing MES 0 from MES 1-3 using the FC cutoff of 60 mcg/g. Sensitivity analysis demonstrated robust results.