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.