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Introduction: Autoimmune metaplastic atrophic gastritis (AMAG) is a precancerous condition that predisposes to gastric neuroendocrine tumors (gNETs). There exist no methods to stratify patients with AMAG for gNET risk., Methods: We identified a cohort of patients with AMAG within a university health system using histopathologic and serologic criteria. We analyzed features predictive of prevalent gNET., Results: We identified 181 patients with AMAG and 41 (22.7%) with prevalent gNET. Gastrin levels were elevated in gNET (1,859.8 vs 679.5 pg/mL, P < 0.001), and gastrin titers demonstrated good discrimination (c = 0.799, 95% CI 0.707-0.892) for gNET., Discussion: Gastrin levels differ significantly between patients with AMAG with and without gNET., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended to encourage question-asking by patients and enhance patient-physician communication. To date, an EoE-specific QPL has not been developed for EoE patients., Aim: To develop a preliminary QPL specific to adults with EoE by incorporating input from international esophageal experts., Methods: Sixteen experts were invited to generate QPL content through a modified Delphi (RAND/University of California, Los Angeles, CA) method consisting of 2 rounds of independent ratings. In round 1, experts provided 5 answers to the prompts "what general questions should patients ask when being seen for EoE?" and "what questions do I not hear patients asking but given my experience, I believe they should be asking?" In round 2, experts rated each question on a 5-point Likert scale, and responses rated as "essential" or "important" (determined by an a priori median threshold of ≥ 4.0) were accepted for the EoE QPL., Results: Ten esophageal experts participated in both rounds. Round 1 generated 100 questions. Questions were combined and modified to reduce redundancy, yielding 57 questions. After round 2, 51 questions (85%) were accepted for inclusion (median value ≥ 4.0) in the final QPL. Questions were then divided into 4 themes based on disease domains: (1) "What is EoE?," (2) "Treatment Options," (3) "Follow-up Surveillance and Long-term Risks," and (4) "Allergy and Genetic Testing." The largest number of questions covered was "What is EoE?" (16/51 or 31%). Questions with the highest agreement median (5.0) included examples such as "what should I do if I get a food impaction?" and "what are the treatment options?", Conclusion: This is the first preliminary EoE QPL developed in the field of medicine. We hope implementation enhances effective patient-physician communication by encouraging patients to ask relevant questions that experts prioritized. Future studies will aim to modify this communication tool by incorporating patient perspectives., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In vitro models of autoimmunity are constrained by an inability to culture affected epithelium alongside the complex tissue-resident immune microenvironment. Coeliac disease (CeD) is an autoimmune disease in which dietary gluten-derived peptides bind to the major histocompatibility complex (MHC) class II human leukocyte antigen molecules (HLA)-DQ2 or HLA-DQ8 to initiate immune-mediated duodenal mucosal injury 1-4 . Here, we generated air-liquid interface (ALI) duodenal organoids from intact fragments of endoscopic biopsies that preserve epithelium alongside native mesenchyme and tissue-resident immune cells as a unit without requiring reconstitution. The immune diversity of ALI organoids spanned T cells, B and plasma cells, natural killer (NK) cells and myeloid cells, with extensive T-cell and B-cell receptor repertoires. HLA-DQ2.5-restricted gluten peptides selectively instigated epithelial destruction in HLA-DQ2.5-expressing organoids derived from CeD patients, and this was antagonized by blocking MHC-II or NKG2C/D. Gluten epitopes stimulated a CeD organoid immune network response in lymphoid and myeloid subsets alongside anti-transglutaminase 2 (TG2) autoantibody production. Functional studies in CeD organoids revealed that interleukin-7 (IL-7) is a gluten-inducible pathogenic modulator that regulates CD8 + T-cell NKG2C/D expression and is necessary and sufficient for epithelial destruction. Furthermore, endogenous IL-7 was markedly upregulated in patient biopsies from active CeD compared with remission disease from gluten-free diets, predominantly in lamina propria mesenchyme. By preserving the epithelium alongside diverse immune populations, this human in vitro CeD model recapitulates gluten-dependent pathology, enables mechanistic investigation and establishes a proof of principle for the organoid modelling of autoimmunity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Goal: The aim was to investigate the short-term impact of time restricted feeding on patients with suspected gastroesophageal reflux disease (GERD)., Background: Lifestyle modifications are often suggested, but the role of diet in GERD is unclear. Intermittent fasting is popular in the media and has demonstrated potential benefits with weight loss and inflammatory conditions as well as alterations in gastrointestinal hormones., Study: Patients who were referred for 96-hour ambulatory wireless pH monitoring off proton pump inhibitor to investigate GERD symptoms were screened for eligibility. Patients were instructed to maintain their baseline diet for the first 2 days of pH monitoring and switch to an intermittent fasting regimen (16 consecutive hour fast and 8 h eating window) for the second 2 days. Objective measures of reflux and GERD symptom severity were collected and analyzed., Results: A total of 25 participants were analyzed. 9/25 (36%) fully adhered to the intermittent fasting regimen, with 21/25 (84%) demonstrating at least partial compliance. Mean acid exposure time on fasting days was 3.5% versus 4.3% on nonfasting days. Intermittent fasting was associated with a 0.64 reduction in acid exposure time (95% CI: -2.32, 1.05). There was a reduction in GERD symptom scores of heartburn and regurgitation during periods of intermittent fasting (14.3 vs. 9.9; difference of -4.46, 95% CI: -7.6,-1.32)., Conclusions: Initial adherence to time restricted eating may be difficult for patients. There is weak statistical evidence to suggest that intermittent fasting mildly reduces acid exposure. Our data show that short-term intermittent fasting improves symptoms of both regurgitation and heartburn., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Integrated relaxation pressure (IRP) calculation depends on the selection of a single gastric reference sensor. Variable gastric pressure readings due to sensor selection can lead to diagnostic uncertainty. This study aimed to examine the effect of gastric reference sensor selection on IRP measurement and diagnosis., Methods: We identified high-resolution manometry (HRM) conducted between January and November 2017 with at least six intragastric reference sensors. IRP measurements and Chicago Classification 3.0 (CCv3) diagnoses were obtained for each of six gastric reference sensors. Studies were categorized as "stable" (no change in diagnosis) or "variable" (change in diagnosis with gastric reference selection). Variable diagnoses were further divided into "variable normal/dysmotility" (≥1 normal IRP measurement and ≥1 CCv3 diagnosis), or "variable dysmotility" (≥1 CCv3 diagnosis, only elevated IRP measurements). Bland-Altman plots were used to compare IRP measurements within HRM studies., Key Results: The analysis included 100 HRM studies, among which 18% had variable normal/dysmotility, and 10% had variable dysmotility. The average IRP difference between reference sensors was 6.7 mmHg for variable normal/dysmotility and 5.9 mmHg for variable dysmotility. The average difference between the proximal-most and distal-most sensors was -1.52 mmHg (lower limit of agreement -10.03 mmHg, upper limit of agreement 7.00 mmHg)., Conclusions & Inferences: IRP values can vary greatly depending on the reference sensor used, leading to inconsistent diagnoses in 28% of HRM studies. Choosing the correct gastric reference sensor is crucial for accurate test results and avoiding misdiagnosis. Standardization of reference sensor selection or supportive testing for uncertain results should be considered., (© 2023 John Wiley & Sons Ltd.)

Introduction: Despite best practice recommendations for managing eosinophilic esophagitis (EoE), variation in care exists., Methods: We used established methodology for quality indicator development to identify metrics to define quality for the treatment of EoE., Results: Among 29 proposed quality indicator statements, 9 (31%) were adopted as highly valid across all categories. Two (22%) of these statements were identified as having existing or suspected quality gaps., Discussion: We identified highly valid EoE quality indicators for adult gastroenterologists, which can be used for quality improvement with resulting benefits for patient outcomes., (Copyright © 2022 by The American College of Gastroenterology.)

In this work, we find that CD8 + T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49 + CD8 + regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8 + T cells efficiently eliminated pathogenic gliadin-specific CD4 + T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR + CD8 + T cells, but not CD4 + regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49 + CD8 + T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8 + T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.