Summary Background Pembrolizumab immunotherapy has been associated with hepatotoxicity in 1%‐10% of oncology patients treated in clinical trials. Aim To describe the incidence, phenotypes and outcomes of liver injury in a large cohort of solid organ tumour patients receiving pembrolizumab Methods Liver injury was defined by serum alanine aminotransferase, alkaline phosphatase, and/or total bilirubin levels exceeding threshold values. The likelihood of drug‐induced liver injury was adjudicated by expert opinion. Results Seventy (14.3%) of the 491 pembrolizumab‐treated patients developed liver injury at a median of 62 days (6‐478) and 71.4% had a cholestatic injury profile at onset. The median age, gender and tumour types of liver injury patients were similar to those without, but hepatic metastases (53% vs 21%, P < 0.01) and prior systemic and liver‐directed therapy (71% vs 53%, P < 0.01) were more commonly observed in liver injury patients. During follow‐up, liver injury patients were less likely to experience tumour remission (10% vs 40.4%) and had higher mortality (67.1% vs 33.7%). Only 20 (28.6%) liver injury cases were adjudicated as probable drug‐induced hepatotoxicity; these patients were significantly more likely to present with an hepatocellular/mixed injury pattern (65% vs 12%), to receive corticosteroids (55% vs 12%) and had lower mortality (45% vs 76%) during follow‐up. Conclusions Oncology patients treated with pembrolizumab who develop liver injury experience poorer outcomes during follow‐up. The low incidence of confirmed drug hepatotoxicity highlights the need for thorough medical evaluation before initiating corticosteroids to optimise patient care.

INTRODUCTION: Duodenal epithelial barrier impairment and immune activation may play a role in the pathogenesis of functional dyspepsia (FD). This study was aimed to evaluate the duodenal epithelium of patients with FD and healthy individuals for detectable microscopic structural abnormalities. METHODS: This is a prospective study using esophagogastroduodenoscopy enhanced with duodenal confocal laser endomicroscopy (CLE) and mucosal biopsies in patients with FD (n = 16) and healthy controls (n = 18). Blinded CLE images analysis evaluated the density of epithelial gaps (cell extrusion zones), a validated endoscopic measure of the intestinal barrier status. Analyses of the biopsied duodenal mucosa included standard histology, quantification of mucosal immune cells/cytokines, and immunohistochemistry for inflammatory epithelial cell death called pyroptosis. Transepithelial electrical resistance (TEER) was measured using Ussing chambers. Epithelial cell-to-cell adhesion proteins expression was assessed by real-time polymerase chain reaction. RESULTS: Patients with FD had significantly higher epithelial gap density on CLE in the distal duodenum than that of controls (P = 0.002). These mucosal abnormalities corresponded to significant changes in the duodenal biopsy samples of patients with FD, compared with controls, including impaired mucosal integrity by TEER (P = 0.009) and increased number of epithelial cells undergoing pyroptosis (P = 0.04). Reduced TEER inversely correlated with the severity of certain dyspeptic symptoms. Furthermore, patients with FD demonstrated altered duodenal expression of claudin-1 and interleukin-6. No differences in standard histology were found between the groups. DISCUSSION: This is the first report of duodenal CLE abnormalities in patients with FD, corroborated by biopsy findings of epithelial barrier impairment and increased cell death, implicating that duodenal barrier disruption is a pathogenesis factor in FD and introducing CLE a potential diagnostic biomarker in FD.

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Irritable bowel syndrome is a common condition that negatively impacts quality of life and results in significant health care expenditures. The vast majority of IBS patients associate their symptoms with eating. Numerous randomized, controlled trials suggest that restriction of dietary FODMAPs improves overall symptoms, abdominal pain, bloating and quality of life in more than half of IBS sufferers. There is emerging data which suggests that other diets (gluten free, guided elimination diets) might also be of benefit to IBS patients. Areas covered: Comprehensive literature review on dietary therapies available for IBS to date and exploration into individualized dietary therapy development based on diagnostic testing. Expert commentary: FODMAP elimination identifies IBS patients who are sensitive to FODMAPs. Responders should undergo a structured reintroduction of foods containing FODMAPs to determine a patient's sensitivities. This information can then be used to create a personalized, less restrictive low FODMAP diet. Future research should focus on the identification of other effective diet therapies focusing on supplementation of functional foods in addition to elimination and the development of biomarker-based diet treatment plans which identify the right treatment for the right patient.

SUMMARY Symptoms of esophageal dysfunction such as food impaction are consistent with, but not diagnostic for eosinophilic esophagitis (EoE) without obtaining histology. We conducted a retrospective study to characterize patients with food impaction at a tertiary center. We hypothesized that many patients with food impaction may be lost to follow-up and that many have features suggestive of EoE. Adult patients presenting to the emergency department with esophageal food impaction were identified from an endoscopic database. Electronic medical records were manually abstracted. We examined associations between demographics, comorbid conditions, and follow-up with biopsy findings. Of 220 patients who presented to the emergency department for food impaction, 74.1% were men. Adequate follow-up was not documented in 120 (54.5%). Those lost to follow-up did not differ significantly by gender, age at symptom onset, or distance from hospital compared to those with follow-up. Esophageal biopsies were obtained in 158 (71.8%), and those with ≥15 eos/HPF were more likely to be lost to follow-up than those with &lt;15 eos/HPF (52.8% vs. 34.8%, P &lt; 0.05). Of those never biopsied, 79.0% were lost to follow-up and had intermediate proportions of males, food allergy, and asthma when compared to those with and without eosinophilic inflammation. Patients with food impaction commonly have EoE but are often lost to follow-up. Among those never biopsied, demographic and clinical features suggest that many may have undiagnosed EoE. Strategies for increasing use of biopsies in patients with food impaction and improving follow-up are needed to diagnose and manage EoE.