Asia Pacific association of gastroenterology consensus statements on histopathological evaluation of inflammatory bowel diseases.

Background: Mucosal histological activity is increasingly valued as a treatment endpoint in inflammatory bowel diseases (IBD). In the Asia Pacific region, the utility and acceptability of IBD histology as a treatment endpoint are uncertain due to the heterogeneity of IBD prevalence, resourcing and level of knowledge among practitioners. There is an opportunity to engage clinicians to harmonise histology reporting and collaborate with pathologists in this field.

Upadacitinib Maintenance Therapy in Crohn's Disease: Final Results From the Randomized Phase 3 U-ENDURE Study.

Background & Aims: Upadacitinib, an oral, reversible Janus kinase inhibitor, demonstrated efficacy and safety in patients with Crohn's disease in 2 phase III induction trials (U-EXCEL and U-EXCEED) and in a primary analysis of the first 502 patients entering the subsequent maintenance trial (U-ENDURE). Here, we present the overall results of the entire population of U-ENDURE (N = 673).

Methods: Clinical responders to 12 weeks of upadacitinib 45 mg once daily (QD) induction were randomized (1:1:1) to receive upadacitinib 15 mg QD (n = 221), upadacitinib 30 mg QD (n = 229), or placebo (n = 223) as maintenance therapy for 52 weeks.

ST6GAL1 promotes IBD B cell recruitment to the inflamed colon in a CD22-dependent mechanism.

Background And Aims: Since the discovery that auto-reactive anti-αvβ6 integrin antibodies are associated with ulcerative colitis, cells from the B cell lineage, especially plasmablasts and plasma cells have increasingly come into the focus of research on inflammatory bowel disease. However, the mechanisms regulating their recruitment from the circulation to the gut remain poorly understood. Here, we explored whether the B cell-specific lectin CD22 interacts with endothelial α2,6-linked sialic acid residues attached by ST6GAL1 to mediate such recruitment in IBD.

IL-36 signaling as a drug target in Crohn's disease patients with IL36RN mutations.

The IL-36 signaling pathway has recently been identified as a key regulator of intestinal homeostasis and inflammation. However, the role of mutations in the IL-36R signaling pathway in the pathogenesis of inflammatory bowel disease remains unclear. We here identified four Crohn's disease patients with heterozygous missense mutations in the IL-36 receptor antagonist (IL36RN, IL-36RA).

An International Consensus on Appropriate Management of Corticosteroids in Clinical Trials in Inflammatory Bowel Disease.

Background & Aims: Approval of new therapies for inflammatory bowel disease (IBD) requires rigorously designed and well-executed randomized controlled trials (RCTs). Corticosteroids remain a cornerstone of IBD induction therapy, and many patients in trials are enrolled while taking corticosteroids. Despite this, approaches to corticosteroid management in RCTs have been highly heterogeneous, often differing from clinical practice.

IBUS-SAS Is a Highly Accurate Intestinal Ultrasound Score for Predicting Endoscopic Disease Activity in Ulcerative Colitis.

Background: The international bowel ultrasound group-segmental activity score (IBUS-SAS) is a validated tool with high interobserver agreement for accurately detecting disease activity in Crohn's disease (CD). Here, we addressed whether the IBUS-SAS is also suitable to assess disease activity in ulcerative colitis (UC).

Methods: The IBUS-SAS and Limberg scores were determined in the sigmoid colon of patients with UC.

IBDome: An integrated molecular, histopathological, and clinical atlas of inflammatory bowel diseases.

Multi-omic and multimodal datasets with detailed clinical annotations offer significant potential to advance our understanding of inflammatory bowel diseases (IBD), refine diagnostics, and enable personalized therapeutic strategies. In this multi-cohort study, we performed an extensive multi-omic and multimodal analysis of 1,002 clinically annotated patients with IBD and non-IBD controls, incorporating whole-exome and RNA sequencing of normal and inflamed gut tissues, serum proteomics, and histopathological assessments from images of H&E-stained tissue sections. Transcriptomic profiles of normal and inflamed tissues revealed distinct site-specific inflammatory signatures in Crohn's disease (CD) and ulcerative colitis (UC).

Diagnosis and Management of Upper Gastrointestinal Involvement in Adult Patients With Crohn's Disease: A Systematic Review.

Background & Aims: The diagnosis and management of ileocolonic Crohn's disease are well-established. In contrast, standardized guidance pertaining to the diagnosis and management of upper gastrointestinal Crohn's disease (UGICD) is lacking, despite its potentially severe consequences. This comprehensive systematic review describes the prevalence, clinical presentation, and medical and surgical management of involvement of the upper GI tract in adult patients with Crohn's disease.

Endoscopic Management of Perforations, Gastrointestinal Leaks, and Fistulae.

Background: Gastrointestinal leaks and fistulae are serious conditions with the potential to be life-threatening, and they are of significant relevance for both endoscopists and surgeons. These conditions may present in a wide variety of ways in clinical settings. These defects may arise from malignant or inflammatory conditions, or may be iatrogenic, occurring after surgery, endoscopic, or radiation therapy.

Integrated multimodel analysis of intestinal inflammation exposes key molecular features of preclinical and clinical IBD.

Background: IBD is a chronic inflammatory condition driven by complex genetic and immune interactions, yet preclinical models often fail to fully recapitulate all aspects of the human disease. A systematic comparison of commonly used IBD models is essential to identify conserved molecular mechanisms and improve translational relevance.

Objective: We performed a multimodel transcriptomic analysis of 13 widely used IBD mouse models to uncover coregulatory gene networks conserved between preclinical colitis/ileitis and human IBD and to define model-specific and conserved cellular, subcellular and molecular signatures.

Expert recommendations to standardize transcriptomic analysis in inflammatory bowel disease clinical trials.

Background And Aims: Substantial methodological and reporting heterogeneity confounds the interpretation and generalizability of transcriptomic data for inflammatory bowel disease (IBD) studies. We aimed to develop recommendations to standardize transcriptomic research in clinical trials.

Methods: A 2-part study was undertaken.

IBDome: An integrated molecular, histopathological, and clinical atlas of inflammatory bowel diseases.

Multi-omic and multimodal datasets with detailed clinical annotations offer significant potential to advance our understanding of inflammatory bowel diseases (IBD), refine diagnostics, and enable personalized therapeutic strategies. In this multi-cohort study, we performed an extensive multi-omic and multimodal analysis of 1,002 clinically annotated patients with IBD and non-IBD controls, incorporating whole-exome and RNA sequencing of normal and inflamed gut tissues, serum proteomics, and histopathological assessments from images of H&E-stained tissue sections. Transcriptomic profiles of normal and inflamed tissues revealed distinct site-specific inflammatory signatures in Crohn's disease (CD) and ulcerative colitis (UC).

Fidaxomicin for Clostridioides difficile infection in patients with inflammatory bowel disease: a multicenter retrospective cohort study.

Background And Aims: Inflammatory bowel disease (IBD) patients with Clostridioides difficile infection (CDI) are at increased risk of adverse outcomes. Data on fidaxomicin use in IBD remain scarce. We assessed the effectiveness and safety of fidaxomicin for CDI and its impact on IBD outcomes in a large international cohort.

Guselkumab binding to CD64 IL-23-producing myeloid cells enhances potency for neutralizing IL-23 signaling.

IL-23 is implicated in the pathogenesis of immune-mediated inflammatory diseases, and myeloid cells that express Fc gamma receptor 1 (FcγRI or CD64) on their surface have been recently identified as a primary source of IL-23 in inflamed tissue. Our complementary analyses of transcriptomic datasets from psoriasis and IBD showed increased expression of CD64 and IL-23 transcripts in inflamed tissue, and greater abundance of cell types with co-expression of CD64 and IL-23. These findings led us to explore potential implications of CD64 binding on the function of IL-23-targeting monoclonal antibodies (mAbs).

Comparative real-world effectiveness of ustekinumab versus anti-TNF in Crohn's disease: 12-month maintenance phase results from the prospective, observational RUN-CD study using propensity score adjustment.

Background: The prospective RUN-CD registry investigates the effectiveness of ustekinumab (UST) and other biologics in Crohn's disease (CD) across Germany. Based on data from the registry, this study presents the maintenance phase results of a 12-month real-world-evidence (RWE) comparison of CD patients initiating new biologic therapies with UST or anti-TNF.

Methods: After excluding patients using biologics other than UST and anti-TNF and those with missing outcomes, the final sample consisted of 618 CD patients.

Accuracy of superb microvascular imaging (SMI) in predicting endoscopic Crohn's disease activity.

Background: Treat-to-target therapy in inflammatory bowel disease requires longitudinal assessment of disease activity and intestinal ultrasound (IUS) is a promising non-invasive and cheap technology to provide objective read-outs. Vascularization of the bowel wall is one key parameter on IUS. While this is conventionally done with Color doppler imaging, it is currently unclear whether microvascular flow imaging techniques might improve the diagnostic performance of IUS.

Superb Microvascular Imaging Is Superior to Doppler Imaging in Ruling Out Ulcerative Colitis Disease Activity.

Background: There is an unmet medical need for noninvasive techniques to determine disease activity in inflammatory bowel disease (IBD) and intestinal ultrasound (IUS) has shown promising performance in this regard. In addition to parameters such as bowel wall thickness, stratification, and mesenteric fat, color Doppler signals are used to determine inflammatory activity in the gut. However, whether superb microvascular imaging (SMI), a microvascular flow imaging technique, improves the diagnostic accuracy is currently unclear.

Discrimination between Inflammatory and Fibrotic Activity in Crohn's Disease-Associated Ileal-Colonic Anastomotic Strictures by Combined Ga-68-FAPI-46 and F-18-FDG-PET/CT Imaging.

Introduction: The development of an intestinal stricture in patients with Crohn's disease represents an important and frequent complication, reflecting the progressive nature of the disease. Depending on the inflammatory and fibrotic composition of the stricture, intensified medical therapy, interventional endoscopy, or surgical intervention is required. However, currently available diagnostic approaches can only assess the level of inflammation, but not the degree of fibrosis, limiting rational therapeutic management of Crohn's disease patients.

Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.

Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, the molecular mechanisms of barrier failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in intestinal epithelial cells (IECs) of patients with IBD and show that impaired fusion is sufficient to drive chronic intestinal inflammation.

Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface.

Aims: The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health.

[Treatment of severe flares in Crohn's disease and ulcerative colitis].

Background: 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.