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Background and Aims: Inflammatory bowel disease [IBD] is associated with high rates of post-colonoscopy colorectal cancer [PCCRC], but further in-depth qualitative analyses are required to determine whether they result from inadequate surveillance or aggressive IBD cancer evolution., Methods: All IBD patients who had a colorectal cancer [CRC] diagnosed between January 2015 and July 2019 and a recent [<4 years] surveillance colonoscopy at one of four English hospital trusts underwent root cause analyses as recommended by the World Endoscopy Organisation to identify plausible PCCRC causative factors., Results: In total, 61% [n = 22/36] of the included IBD CRCs were PCCRCs. They developed in patients with high cancer risk factors [77.8%; n = 28/36] requiring annual surveillance, yet 57.1% [n = 20/35] had inappropriately delayed surveillance. Most PCCRCs developed in situations where [i] an endoscopically unresectable lesion was detected [40.9%; n = 9/22], [ii] there was a deviation from the planned management pathway [40.9%; n = 9/22], such as service-, clinician- or patient-related delays in acting on a detected lesion, or [iii] lesions were potentially missed as they were typically located within areas of active inflammation or post-inflammatory change [36.4%; n = 8/22]., Conclusions: IBD PCCRC prevention will require more proactive strategies to reduce endoscopic inflammatory burden, and to improve lesion optical characterization, adherence to recommended surveillance intervals, and patient acceptance of prophylactic colectomy. However, the significant proportion appearing to originate from non-adenomatous-looking mucosa which fail to yield neoplasia on biopsy yet display aggressive cancer evolution highlights the limitations of current surveillance. Emerging molecular biomarkers may play a role in enhancing cancer risk stratification in future clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked by expansion of resident mucosal IFNγ cytotoxic CD8 + T cells, but how these arise is unclear. Here, we track CPI-bound T cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST). Target occupancy was increased in inflamed tissue, with drug-bound T cells located in distinct microdomains distinguished by specific intercellular signaling and transcriptional gradients. CPI-bound cells were largely CD4 + T cells, including enrichment in CPI-bound peripheral helper, follicular helper, and regulatory T cells. IFNγ CD8 + T cells emerged from both tissue-resident memory (TRM) and peripheral populations, displayed more restricted target occupancy profiles, and co-localized with damaged epithelial microdomains lacking effective regulatory cues. Our multimodal analysis identifies causal pathways and constitutes a resource to inform novel preventive strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Ustekinumab is an interleukin-12/interleukin-23 receptor antagonist licensed for the treatment of ulcerative colitis (UC). Clinical trial data were promising; however, real-world data are limited. We assessed the safety and effectiveness of ustekinumab in UC in a real-world setting., Design/method: This was a multicentre, retrospective, observational cohort study between February 2020 and January 2022. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical remission was defined as a SCCAI≤2. The primary endpoints were rates of corticosteroid-free remission (CSFR) at week 16 and at week 26. Objective outcomes, including faecal calprotectin (FCAL), were also collected., Results: 110 patients with UC (65% male; median age 40 (IQR range 29-59); 96% with prior biologic and/or tofacitinib exposure) had a median follow-up of 28 weeks (IQR 17-47). CSFR was 36% (18/50) at week 16% and 33% (13/39) at week 26, corresponding with a significant fall in SCCAI from 6 (IQR 4-8) at baseline to 3 (IQR 0-5) at week 26, p<0.001. By week 16, there was improvement of median FCAL measurements, which fell from a baseline of 610 µg/g (IQR 333-1100) to 102 µg/g (IQR 54-674) at week 16. At the end of follow-up, 15% (17/110) had discontinued treatment; 13 patients due to primary non-response or loss of response, and 1 patient for family planning. Treatment was discontinued in three patients due to adverse events., Conclusion: In the largest real-world study to date, ustekinumab was effective with a reassuring safety profile in a refractory cohort of patients., Competing Interests: Competing interests: SH has served as a speaker, a consultant, and/or advisory board member for Pfizer, Janssen, Abbvie and Takeda, with research supported by Pfizer and Galápagos NV. AB has received speaker fees from Takeda and meeting support fees from Abbvie, Dr Falk and Vifor Pharma. KBK served as a speaker, a consultant, and/or advisory board member for Janssen, Takeda, PredictImmune, Galapagos, Ferring, and Amgen. KP has received honoraria for educational meetings and speaker fees from Abbvie, Janssen, Takeda, DrFalk, PredictImmune and Ferring and has received advisory board fees from Abbvie, Galapagos and Janssen. PMI has received lecture fees from Abbvie, Warner Chilcott, Ferring, Falk Pharma, Takeda, MSD, Johnson and Johnson, Shire, and Pfizer, financial support for research from MSD, Takeda, and Pfizer, advisory fees from Abbvie, Warner Chilcott, Takeda, MSD, Vifor Pharma, Pharmacosmos, Topivert, Genentech, Hospira, and Samsung Bioepis. MAS served as a speaker, a consultant, and/or an advisory board member for Sandoz, Janssen, Takeda, MSD, Falk, Abbvie, Bristol Myers Squibb, Galapagos, and Samsung Bioepis. LA-H, SB, LM, RL and AW report no conflicts of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Although COVID-19 was first recognised as an acute respiratory illness, extra-pulmonary manifestations are increasingly being recognised. Acute gastrointestinal side effects have been well reported with COVID-19 infection and are estimated to affect around 17% of patients. With COVID-19 still being a relatively new illness, the chronic gastrointestinal symptoms are less well characterised. Post-infectious irritable bowel syndrome (IBS) can occur following bacterial and viral infections, and with ACE-2 receptors being shown to be present in the gastrointestinal tract and SARS-Cov-2 RNA being present in stool, SARS-CoV-2 is now appreciated as an enteric pathogen. In our study, we survey acute and chronic gastrointestinal symptoms after COVID-19 infection. We have conducted one of the few UK studies on gastrointestinal symptoms, with the longest follow-up duration of 6 months. We have found that gastrointestinal symptoms are common at 6 months, affecting 43.8% of our patients. Further research is needed to explore whether this represents a new post-COVID-19 IBS, which has not previous been described in the literature, including its clinical course and response to any potential medical therapies., (© Royal College of Physicians 2022. All rights reserved.)

Background & Aims: The pathogenesis of immune checkpoint inhibitor (ICI)-colitis remains incompletely understood. We sought to identify key cellular drivers of ICI-colitis and their similarities to idiopathic ulcerative colitis, and to determine potential novel therapeutic targets., Methods: We used a cross-sectional approach to study patients with ICI-colitis, those receiving ICI without the development of colitis, idiopathic ulcerative colitis, and healthy controls. A subset of patients with ICI-colitis were studied longitudinally. We applied a range of methods, including multiparameter and spectral flow cytometry, spectral immunofluorescence microscopy, targeted gene panels, and bulk and single-cell RNA sequencing., Results: We demonstrate CD8 + tissue resident memory T (T RM ) cells are the dominant activated T cell subset in ICI-colitis. The pattern of gastrointestinal immunopathology is distinct from ulcerative colitis at both the immune and epithelial-signaling levels. CD8 + T RM cell activation correlates with clinical and endoscopic ICI-colitis severity. Single-cell RNA sequencing analysis confirms activated CD8 + T RM cells express high levels of transcripts for checkpoint inhibitors and interferon-gamma in ICI-colitis. We demonstrate similar findings in both anti-CTLA-4/PD-1 combination therapy and in anti-PD-1 inhibitor-associated colitis. On the basis of our data, we successfully targeted this pathway in a patient with refractory ICI-colitis, using the JAK inhibitor tofacitinib., Conclusions: Interferon gamma-producing CD8 + T RM cells are a pathological hallmark of ICI-colitis and a novel target for therapy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Histoacryl glue is used increasingly for the treatment of gastric and ectopic varices, and there is experience in its use for oesophageal varices. It is an effective treatment, yet numerous reports of complications have accumulated. This review of the literature describes the technique, explores circulatory and vascular consideration unique to portal hypertension and categorises the complications into: "Embolisation", "local venous thrombosis", "fistulisation and extravascular injection", "ulceration, erosion and extrusion", and "nidus of infection". A case is then made for standardisation of the technique and the consent process., Competing Interests: Conflict-of-interest statement: None.