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 þ tissue resident memory T (T RM ) cells are the dominant activated T cell subset in ICIcolitis. The pattern of gastrointestinal immunopathology is distinct from ulcerative colitis at both the immune and Gastroenterology 2021;161:1229-1244 BASIC AND TRANSLATIONAL AT epithelial-signaling levels. CD8 þ T RM cell activation correlates with clinical and endoscopic ICI-colitis severity. Single-cell RNA sequencing analysis confirms activated CD8 þ 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 ICIcolitis, using the JAK inhibitor tofacitinib. CONCLUSIONS: Interferon gamma-producing CD8 þ T RM cells are a pathological hallmark of ICI-colitis and a novel target for therapy.

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.

ObjectiveUstekinumab 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/methodThis 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.Results110 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.ConclusionIn the largest real-world study to date, ustekinumab was effective with a reassuring safety profile in a refractory cohort of patients.

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.

Background: Anti-tumour necrosis factor therapy is an established treatment for moderate-to-severely active ulcerative colitis (UC). Recent network meta-analyses of controlled trial data have indicated a superiority of intravenous drugs (infliximab) over subcutaneous (adalimumab). We conducted a retrospective multi-centre cohort study to determine the comparative effectiveness of these two drugs.Methods: Patients with UC administered infliximab or adalimumab as their first biologic, identified from the therapy databases of five UK hospitals, were included, if they had completed induction and were on maintenance treatment. Patients receiving infliximab as 'rescue' therapy for acute severe UC were excluded. The primary end-points for comparison were the number of patients remaining on initial therapy (infliximab or adalimumab) at 52 weeks and the number of patients in clinical remission at 52 weeks (Simple Clinical Colitis Activity [SCCAI] score ≤ 3).Results: Seventy-eight infliximab and 63 adalimumab patients were analysed. At 52 weeks, 83% of infliximab patients and 59% of adalimumab patients remained on therapy (P = 0.001). At 52 weeks, 62% of the infliximab group were in clinical remission compared to 32% of the adalimumab group (P = 0.0004). Primary nonresponse was reported in 24% of adalimumab patients and 5% of infliximab patients (P = 0.001). There were no significant differences in colectomy rates or hospital admission for acute flares at 52 weeks. Conclusions:Our real-world results affirm the findings of network meta-analyses of clinical trials, suggesting that infliximab is superior to adalimumab in the maintenance of remission in UC up to 52 weeks. How to cite this article: Kronsten VT, Colwill MJ, Nayeemuddin S, et al. A 'real-world' retrospective multi-centre cohort study comparing infliximab and adalimumab for the maintenance of remission in ulcerative colitis. GastroHep.

steroids therapy, the second patient underwent surgery for a malignant stricture and the third patient had enteroscopy and removal of the capsule; biopsies of the stricture were in-conclusive. The overall cohort DY for all indications was 39% (n=377/958). Conclusions This is the largest series from a DGH in England. Our data has shown that CE is safe, non-invasive and feasible in a district hospital setting. It has a good DY, acceptable to patient and allows adequate look at the small bowel. Recommendations: Despite the major role of CE in GI investigation, there is a lack of structured training. We recommend formal accreditation and training to be added to the Gastroenterology advance training curriculum.

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Background Real time monitoring of patients with Crohn’s disease (CD) gives us the opportunity to examine disease trajectory. We have demonstrated the feasibility of using a monitoring platform with patient reported data, collected prospectively and routinely in clinical practice. The question is whether it can be used for specific drugs Methods TrueColours-IBD (TC-IBD)is a real time, web based platform that through email prompts linked to questionnaires, collects longitudinal patient reported outcome measures (for CD, symptoms measured by Harvey Bradshaw Index (HBI) and quality of life by IBD Control-8). It is routinely used by &gt;2000 patients in Oxford. This study examined 114 patients with Crohn’s: 45 males (median age 36, IQR 28–51) and 69 females (median age 34.8, IQR 28–47), treated with ustekinumab for a maximum of 16 months (range -2 months to 14 months). A linear mixed-effects model was used to approximate longitudinal trends of HBI and IBD Control-8. 3 individual items of the HBI scale (general well-being, abdominal pain & stool frequency) were also assessed. The TC-IBD platform has the capacity to analyse and show patients’ data automatically, using customised models and algorithms through the feedback loop (Fig 1). Model coefficients, intercept and slope were estimated using the restricted maximum likelihood (REML) approach. The intercept corresponds to the expected cohort mean value of the scale (e.g. HBI, IBD Control-8) at baseline (time zero) and the slope describes the rate of the change over time Results The models’ coefficients, the intercept and slope of both HBI and IBD Control-8 scales were statistically significant and are summarised in Table 1 with confidence intervals. Both linear trends (slopes) describing HBI (p&lt;0.001) and IBD Control-8 (p&lt;0.001) confirmed improvements for patients. The bowel movement component of the HBI dominated over general well-being and abdominal pain, while keeping a similar downward trend over time ( Fig 2 and Fig 3a,b) Conclusion Patient reported data through the TC-IBD platform can be used for statistical analyses and continuous monitoring of drug effect over time. This analysis is limited by a lack of comparator group, but the models may be used with the TrueColours platform as a decision support tool for other drugs