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Summary: There are conflicting data assessing the impact of isolated post‐operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post‐operative Crohn's disease (CD) patients with isolated anastomotic disease. Methods: Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post‐operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post‐operative follow‐up. Secondary outcome was surgical recurrence. Results: One hundred and ninety‐nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0‐i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0‐i2b (P = 0.86). Conclusion: Post‐operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies. [ABSTRACT FROM AUTHOR]

Summary: Background: Ozanimod, a high selective sphingosine 1 phosphate (S1P) receptor (S1PR) 1/5 modulator was approved by the Food and Drug Administration for the treatment of adult patients with moderately to severely active ulcerative colitis. Additional S1PR modulators are being tested in clinical development programmes for both ulcerative colitis and Crohn's disease. Aim: To provide an overview of advances in understanding S1PRs biology and summarise preclinical and clinical investigations of S1P receptor modulators in chronic inflammatory disease with special emphasis on inflammatory bowel diseases (IBD). Methods: We performed a narrative review using PubMed and ClinicalTrials.gov. Results: Through S1PRs, S1P regulates multiple cellular processes, including proliferation, migration, survival, and vascular barrier integrity. The S1PRs function of regulating lymphocyte trafficking is well known, but new functions of S1PRs expand our knowledge of S1PRs biology. Several S1PR modulators are in clinical development for both ulcerative colitis and Crohn's disease and have shown promise in phase II and III studies with ozanimod now being approved for ulcerative colitis. Conclusions: S1P receptor modulators constitute a novel, promising, safe, and convenient strategy for the treatment of IBD. [ABSTRACT FROM AUTHOR]

The incidence of inflammatory bowel diseases (IBD) worldwide has resulted in a global public health challenge. Intestinal fibrosis leading to stricture formation and bowel obstruction is a frequent complication in Crohn's disease (CD), and the lack of anti‐fibrotic therapies makes elucidation of fibrosis mechanisms a priority. Progress has shown that mesenchymal cells, cytokines, microbial products, and mesenteric adipocytes are jointly implicated in the pathogenesis of intestinal fibrosis. This recent information puts prevention or reversal of intestinal strictures within reach through innovative therapies validated by reliable clinical trial endpoints. Here, we review the role of immune and non‐immune components of the pathogenesis of intestinal fibrosis, including new cell clusters, cytokine networks, host‐microbiome interactions, creeping fat, and their translation for endpoint development in anti‐fibrotic clinical trials. [ABSTRACT FROM AUTHOR]

Summary: Background: Evidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon‐assisted enteroscopy is scarce. Aim: To evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon‐assisted enteroscopy. Methods: Citations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta‐analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome‐relevant risk factors. Results: In the pooled per‐study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short‐term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow‐up, 48.3% of patients reported symptom recurrence, 38.8% were re‐dilated and 27.4% proceeded to surgery. On the per‐patient‐based multivariable analysis, that patients with disease activity in the small intestine had lower short‐term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14‐0.73, P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09‐3.13, P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34‐2.34, P < 0.001). Conclusions: Balloon‐assisted enteroscopy for dilatation of CD‐associated small intestinal strictures has high short‐term technical and clinical efficacy and low complication rates. However, up to two‐thirds of patients need re‐dilation or surgery. [ABSTRACT FROM AUTHOR]

Summary: Background: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). Aim: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. Methods: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. Results: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%‐41.3%) and 18.5% (95% CI: 8.3%‐36.2%), respectively over a median follow‐up of 23 months (range 5.5‐105.8), and 21.8 months (range 5‐47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%‐77.3%) over a median follow‐up of 21.8 months (range 5‐47). Conclusions: There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery. [ABSTRACT FROM AUTHOR]

Summary: Background: Zymogen granule glycoprotein 2 (GP2) is a major autoantigen of Crohn's disease‐specific pancreatic autoantibodies. Aim: To test a link between loss of tolerance to isoforms of GP2 and pouch disorders in a cross‐sectional study in ulcerative colitis patients with ileal pouch‐anal anastomosis (IPAA). Methods: Serum samples of 117 consecutive ulcerative colitis patients after IPAA were tested for presence of Anti‐GP2 isoforms 1 (GP21) & 4 (GP24) IgG and IgA as well as anti‐Saccaromyces cervisiae (ASCA) IgG and IgA antibodies in a blinded fashion via enzyme‐linked immunosorbent assay. Pouch disorders were diagnosed based on clinical, endoscopic, histological and radiographic criteria. Crohn's disease of the pouch was defined as involvement of the small bowel mucosa proximal to the ileal pouch with Crohn's disease, development of perianal complications or pouch fistula more than 3 months after ileostomy closure. Results: Positivity and level of Anti‐GP21 IgG (AUC 0.77; P < 0.001 & P = 0.02, respectively), Anti‐GP24 IgG (AUC 0.74; P < 0.001 & P = 0.025, respectively) and Anti‐GP24 IgA (AUC 0.77; P < 0.001 to P = 0.018, respectively) were specifically associated with Crohn's disease of the pouch. Anti‐GP2 was not associated with endoscopic or histological pouch disease activity index. Neither positivity nor levels of ASCA IgG (AUC 0.63; P = 0.12 & P = 0.35, respectively) or ASCA IgA (AUC 0.67; P = 0.38 & P = 0.53) were associated with pouch phenotypes. Conclusions: The novel anti‐GP21 and GP24 antibodies are associated with Crohn's disease of the pouch in ulcerative colitis patients after IPAA. Serological anti‐GP2 antibodies could aid in diagnosis of Crohn's disease of the pouch. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Falloon et al papers. To view these articles, visit https://doi.org/10.1111/apt.16853 and https://doi.org/10.1111/apt.16882 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Wang et al papers. To view these articles, visit https://doi.org/10.1111/apt.16741 and https://doi.org/10.1111/apt.16888 [ABSTRACT FROM AUTHOR]

Fibrosis, the excessive accumulation of extracellular matrix and mesenchymal cells, is a common major pathway to organ injury and failure.1 Fibrosis can affect virtually any organ of the body ultimately leading to organ failure, which accounts for at least one-third of deaths worldwide.2 Intestinal fibrosis and associated complications such as intestinal strictures are common in patients with Crohn's disease (CD) and ulcerative colitis.3 Despite progress in anti-inflammation therapy such as biological therapies, the percentage of patients undergoing surgery has remained largely unchanged over time.4 Endoscopic intervention or surgery may provide intermittent relief of symptoms to patients with CD-associated intestinal strictures. To this end, cross-sectional imaging modalities such as magnetic resonance enterography and bowel ultrasound have been investigated to distinguish inflammation from fibrosis and grade their severity.11 Other than basic descriptive information such as pre-stenotic dilation and luminal narrowing, high-dimensional data may be extracted from cross-sectional images, which has led to the use of the term "radiomics." Assessment of Crohn's disease-associated small bowel strictures and fibrosis on cross-sectional imaging: a systematic review. [Extracted from the article]

Linked Content This article is linked to Morar et al and Kamm papers. To view these articles visit https://doi.org/10.1111/apt.13388 and https://doi.org/10.1111/apt.14987. [ABSTRACT FROM AUTHOR]

Background: Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross-sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri-enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed., Aims: To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition., Methods: We searched four databases up to 6 January 2024. Two-stage screening was done in duplicate. We assessed risk of bias using QUADAS-2., Results: There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation., Conclusions: This systematic review is the first step for a structured program to develop a stricture IUS index for CD., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background and Aims: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited., Methods: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds., Results: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence., Conclusions: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs., (© 2022 John Wiley & Sons Ltd.)