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Background: High placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain., Aims: To inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs)., Methods: We updated a Cochrane systematic review and meta-analysis, searching multiple databases to January 1, 2024, to identify placebo-controlled RCTs evaluating medical therapies for patients with eosinophilic oesophagitis. The primary outcome was the pooled proportion of study-defined clinical, endoscopic and histologic responders and remitters randomised to placebo, using an intention-to-treat approach and random-effects model. Sources of heterogeneity were explored using meta-regression., Results: We included 25 RCTs. The pooled proportion of clinical response was 41.0% [95% CI: 29.7%-52.8%] with substantial heterogeneity (I 2  = 74.9%). On meta-regression, older age and a higher probability of being randomised to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC] ≤ 6 eosinophils per high power field [HPF] or ≤ 1 eosinophil/HPF was 4.3% [95% CI: 2.6%-6.2%] (I 2  = 23.6%) and 1.3% [95% CI: 0.5%-2.5%] (I 2  = 0%), respectively. The standardised mean difference in the Eosinophilic Oesophagitis Endoscopic Reference Score to placebo was -0.25 [95% CI: -0.41, -0.10]., Conclusions: Over 40% of patients in eosinophilic oesophagitis trials respond clinically to placebo, and this is associated with trial design factors such as randomisation ratio and trial population. Objective endoscopic and histologic measures are associated with very low placebo responses., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: Peroral endoscopic myotomy (POEM) may result in a distended distal esophagus, referred to as a blown-out myotomy (BOM), the relevance of which is uncertain. The aim of this study was to investigate the prevalence, risk factors, and associated symptoms of BOM after achalasia treatment., Methods: A data set of the locally treated patients in a randomized controlled trial comparing POEM with pneumatic dilation (PD) was analyzed. A BOM is defined as a >50% increase in esophageal diameter at its widest point in the distal esophagus between the lower esophageal sphincter and 5 cm above., Results: Seventy-four patients were treated in our center, and 5-year follow-up data were available in 55 patients (32 patients [58%] randomized to POEM, 23 [42%] PD). In the group initially treated with POEM, the incidence of BOM increased from 11.5% (4/38) at 3 months, to 21.1% (8/38) at 1 year, 27.8% (10/36) at 2 years, and 31.3% (10/32) at 5 years. None of the patients treated with PD alone developed a BOM. Patients who developed a BOM had a higher total Eckardt score and Eckardt regurgitation component compared with patients who underwent POEM without BOM development (3 [2.75-3.25] vs 2 [1.75-3], P = 0.032, and 1 [0.75-1] vs 0 [0-1], P = 0.041). POEM patients with a BOM more often report reflux symptoms (85% [11/13] vs 46% [2/16], P = 0.023) and had a higher acid exposure time (24.5% [8-47] vs 6% [1.2-18.7], P = 0.027)., Discussion: Thirty percent of the patients treated with POEM develop a BOM, which is associated with a higher acid exposure, more reflux symptoms, and symptoms of regurgitation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of 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.)

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the "atopic march" picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation.

Background: Previous studies suggested that antireflux mucosectomy (ARMS) is effective in reducing reflux symptoms and total acid exposure, although the mechanism is unknown. Our objective was to investigate the effect of ARMS on reflux parameters and its mechanism of action., Methods: Gastroesophageal reflux disease (GERD) patients with insufficient symptom control despite a twice-daily proton pump inhibitor (PPI) underwent a piecemeal multiband mucosectomy of 50% of the circumference of the esophagogastric junction (EGJ), extending 2 cm into the cardia. The primary end point was the total number of reflux episodes during 24-hour pH-impedance studies., Results: 11 patients (8 men; median age 37 [interquartile range (IQR) 32-57] years) were treated, with one patient subsequently lost to follow-up. ARMS reduced the median (IQR) number of total reflux episodes (74 [60-82] vs. 37 [28-66]; P = 0.008) and total acid exposure time (8.7% [6.4%-12.7%] vs. 5.3% [3.5%-6.7%]; P = 0.03). Treatment reduced the median (IQR) number of transient lower esophageal sphincter relaxations (TLESRs) during a 90-minute postprandial period (4 [1-8] vs. 2 [1-4]; P = 0.03) and reflux symptom scores (3.6 [3.6-3.9] vs. 1.6 [0.7-2.7]; P = 0.005). Treatment did not increase the mean (SD) dysphagia scores (8.2 [7.3] vs. 8.5 [6.5]) or change the EGJ distensibility on impedance planimetry (4.4 [2.1] vs. 4.3 [2.2] mm2/mmHg). One delayed post-procedural bleed requiring repeat endoscopy occurred (10%); no strictures developed., Conclusion: ARMS is an effective treatment option in PPI-refractory GERD, reducing acid exposure, reflux episodes, and symptoms. While its working mechanism could not be explained by a difference in distensibility, a reduction in TLESRs might play a role., Competing Interests: R.E. Pouw has received consulting fees for Medtronic BV and Micro-Tech Endoscopy, and speaker's fees from Pentax BV. A.J. Bredenoord has received research funding from Norgine, DrFalkPharma, Thelial, Sanofi/Regeneron, and SST, and speaker's and/or consulting fees from Laborie, Medtronic, BMS, Dr. Falk Pharma, Reckitt, Aqilion, Eupraxia, Alimentiv, Sanofi/Regeneron, and AstraZeneca. R.A.B. Oude Nijhuis and T. Kuipers declare that they have no conflicting interests., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Purpose of Review: To review recent publications on the inability to belch syndrome., Recent Findings: Five recent retrospective case series indicate that the inability to belch syndrome usually starts in early childhood and is often accompanied by gurgling noises in the chest, pain in the chest or upper abdomen, bloating, and excessive flatulence. Currently, the vast majority of patients who have been identified with inability to belch have self-diagnosed the syndrome on the basis of information available on the internet. A favorable response to injection of botulinum toxin in the cricopharyngeus muscle is regarded as confirmation of the diagnosis. In a mechanistic study in eight patients, absence of reflexogenic relaxation of the upper esophageal sphincter upon rapid gaseous esophageal distension was confirmed to play a pivotal role in the pathogenesis of the syndrome., Summary: The inability to belch syndrome, caused by failure of the upper esophageal sphincter to relax when the esophageal body is distended, clearly exists and may not be as rare as thought hitherto. However, overdiagnosis is also likely to occur because the diagnosis is usually made on the basis of symptoms only. The efficacy of botulinum toxin injection in the upper sphincter needs to be assessed in double-blind placebo-controlled studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We aimed to assess the clinical practices and adherence to guidelines for adult Eosinophilic Esophagitis (EoE) patients in Europe., Methods: A cross-sectional web survey containing 23 questions was distributed to members of the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract (EUREOS) and the Italian Association of Hospital Gastroenterologists and digestive endoscopists (AIGO). We conducted a subgroup analysis to assess the impact of EoE expertise and practice setting on clinical practices., Results: 228 physicians from 18 European countries participated. Adherence to guidelines varied from 72% to 98.6%. 83.4% of total respondents obtained ≥ 6 esophageal biopsies in suspected EoE. 42% of total respondents, 82.5% of EoE experts (vs. non-experts 33%; P < 0.0001), and 55% of academics (vs. 29.1 non-academics; P < 0.0001) routinely used the EREFS score. Regarding first-line therapy, 82.9% of total respondents prescribed proton pump inhibitors, 41.6% topical steroids, 20.6% elimination diets, and 9.2% combination therapies. Only 72% of respondents used symptoms and endoscopy with <15 Eosinophils/HPF to define treatment response. 21.5% of all respondents did not prescribe maintenance therapies and 12.7% discontinued therapy before response evaluation endoscopy., Conclusion: Our findings revealed significant heterogeneity in practice patterns and suboptimal adherence to EoE guidelines across Europe. Expertise in EoE and working in an academic hospital positively influenced clinical practices and adherence to guidelines., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in parts A and B of the LIBERTY EoE TREET (NCT03633617) study., Methods: The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of nondysphagia symptoms), EoE Impact Questionnaire (impact of EoE on HRQoL), and Patient Global Impression of Severity and Patient Global Impression of Change of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo., Results: At week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] part A -1.7 [-2.9, -0.5], part B -1.4 [-2.3, -0.5]; both P < 0.01) and EoE-SQ Severity (part A -2.0 [-3.9, 0.0], P < 0.05, part B -1.5 [-3.0, 0.1], P = 0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE Impact Questionnaire average scores and improved individual item scores at week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the Patient Global Impression of Change of dysphagia vs placebo or reported having no symptoms per the Patient Global Impression of Severity of dysphagia at week 24., Discussion: Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear., Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24., Results: A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events., Conclusions: In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Peroral endoscopic myotomy (POEM) is an effective and safe treatment for achalasia, but often leads to posttreatment gastroesophageal reflux disease. The aim of this study was to examine the incidence and severity of reflux esophagitis after POEM and to identify associated predictive factors., Methods: Patients who underwent POEM between August 2011 and December 2022 were included. Multivariate logistic regression was used to assess predictive factors for reflux esophagitis after POEM., Key Results: In total, 252 patients were included; of which, 46% were female and age ranged between 18 and 87 years. Reflux esophagitis within 1 year after POEM was observed in 131 patients (52%), which was severe in 29 patients (LA grade C/D, 12%). Length of full-thickness myotomy (cm; OR 1.11, 95% CI 1.02-1.21), Eckardt scores before POEM (OR 0.84, 95% CI 0.74-0.96), previous pneumatic dilation (OR 0.51, 95% CI 0.29-0.91), and previous laparoscopic Heller myotomy (LHM; OR 0.44, 95% CI 0.23-0.86) were associated with reflux esophagitis after POEM. Alcohol use (none vs > 7 units per week; OR 3.51, 95% CI 1.35-9.11) and overweight (BMI ≥25 kg/m 2 ; OR 2.67, 95% CI 1.17-6.09) were positive predictive factors and previous LHM (OR 0.13, 95% CI 0.02-0.95) was a negative predictive factor for severe reflux esophagitis after POEM (LA grade C/D)., Conclusion: About half of the patients develop reflux esophagitis after POEM and 12% is graded as severe. Recognizing predictive factors of reflux esophagitis after POEM treatment leads to better patient selection before POEM and provides an opportunity to take preventive measures or start preemptive treatment., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Measuring health-related quality of life (HRQOL) gained relevance in research and clinical practice in patients with eosinophilic esophagitis. The physical discomfort and social and psychological consequences of this food-related disease substantially affect HRQOL. Determinant of an impaired HRQOL include symptom severity, disease duration, biological disease activity, and psychological factors. Patients prioritize symptom relief and improved HRQOL as treatment objectives. Available treatment options can address these goals; however, there is a suboptimal adherence to treatment. There is a need for enhanced patient guidance and education. The assessment of HRQOL will help to prioritize patient's needs in management., Competing Interests: Disclosure No sources of funding were used to conduct this study or to prepare this article. M.L. van Klink has no conflicts of interest that are directly relevant to the content of this article, A.J. Bredenoord has received research funding from Nutricia, United States, Norgine, Netherlands, Thelial, Sanofi, United States/Regeneron, SST, and Dr Falk Pharma and received speaker and/or consulting fees from Laborie, Medtronic, Dr Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Reckitt and AstraZeneca. A.J. Bredenoord is supported by Vidi grant 91718300 from the Netherlands Organisation for Scientific Research NWO., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of Interest EMW has nothing to declare. SN received consultancy fees from Ipsen and Truvion. GMCM has nothing to declare. BAJB has nothing to declare. PF received consultancy from Cook Medical and Olympus. AJB received research funding from Norgine, DrFalkPharma, Thelial, Sanofi/Regeneron and SST and received speaker and/or consulting fees from Laborie, Medtronic, BMS, Dr. Falk Pharma, Reckitt, Aqilion, Eupraxia, Alimentiv, Sanofi/Regeneron and AstraZeneca.

Objectives: It is thought that esophageal hypersensitivity in combination with an impaired mucosal barrier function contributes to PPI-resistant reflux symptoms. Ziverel, a bioadhesive agent that coats the esophageal wall, was shown to have a positive effect on reflux symptoms. However, the mechanisms of action are unclear. We aimed to assess the effect of Ziverel on esophageal sensitivity to acid and mucosal barrier function., Methods: We performed a double-blind randomized placebo-controlled crossover trial in PPI-refractory patients with reflux symptoms. Patients were assigned (1:1) to 14 days of Ziverel followed by 14 days of placebo or opposite treatment order. The effect was evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy (ETIS) and esophageal biopsies. The primary outcome was the esophageal sensitivity based on perfusion sensitivity score. Secondary outcomes included mucosal barrier function and reflux symptoms and correlations between the different outcomes., Results: Perfusion sensitivity score was not significantly different during treatment with Ziverel (106 (73-115)) and placebo (102 (67-110)) ( p  = 0.508) along with total RDQ score (2.6 (1.9-3.3) vs 2.8 (1.6-3.5) p  = 0.456). ETIS showed comparable values during treatment with Ziverel (13514 (8846-19734)Ω·m) and placebo (13217 (9127-24942)Ω·m ( p  = 0.650)). Comparing Ziverel and placebo no difference was seen in transepithelial electrical resistance (TEER) 203 (163-267) Ω.cm 2 vs 205 (176-240) Ω.cm 2 ( p  = 0.445) and fluorescein flux 775 (17-6964) nmol/cm 2 /h vs 187 (4-12209) nmol/cm 2 /h ( p  = 0.638)., Conclusion: Ziverel did not show a benefit on acid sensitivity, reflux symptoms or esophageal mucosal integrity compared to placebo in PPI-refractory patients with reflux symptoms. Trial registration : Netherlands Trial Register number: NL7670.

Objective: As achalasia is a chronic disorder, long-term follow-up data comparing different treatments are essential to select optimal clinical management. Here, we report on the 10-year follow-up of the European Achalasia Trial comparing endoscopic pneumodilation (PD) with laparoscopic Heller myotomy (LHM)., Design: A total of 201 newly diagnosed patients with achalasia were randomised to either a series of PDs (n=96) or LHM (n=105). Patients completed symptom (Eckardt score) and quality-of-life questionnaires, underwent functional tests and upper endoscopy. Primary outcome was therapeutic success defined as Eckardt score < 3 at yearly follow-up. Secondary outcomes were the need for retreatment, lower oesophageal sphincter pressure, oesophageal emptying, gastro-oesophageal reflux and the rate of complications., Results: After 10 years of follow-up, LHM (n=40) and PD (n=36) were equally effective in both the full analysis set (74% vs 74%, p=0.84) and the per protocol set (74% vs 86%, respectively, p=0.07). Subgroup analysis revealed that PD was superior to LHM for type 2 achalasia (p=0.03) while there was a trend, although not significant (p=0.05), that LHM performed better for type 3 achalasia. Barium column height after 5 min at timed barium oesophagram was significantly higher for patients treated with PD compared with LHM, while other parameters, including gastro-oesophageal reflux, were not different., Conclusions: PD and LHM are equally effective even after 10 years of follow-up with limited risk to develop gastro-oesophageal reflux. Based on these data, we conclude that PD and LHM can both be proposed as initial treatment of achalasia., Competing Interests: Competing interests: GEB is Associate Editor of this journal., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Exposure of the esophageal mucosa to food allergens can cause acute mucosal responses in patients with eosinophilic esophagitis (EoE), but the underlying local immune mechanisms driving these acute responses are not well understood., Objective: We sought to gain insight into the early transcriptomic changes that occur during an acute mucosal response to food allergens in EoE., Methods: Bulk RNA sequencing was performed on esophageal biopsy specimens from adult patients with EoE (n = 5) collected before and 20 minutes after intramucosal injection of various food extracts in the esophagus. Baseline biopsy specimens from control subjects without EoE (n = 5) were also included., Results: At baseline, the transcriptome of the patients with EoE showed increased expression of genes related to an EoE signature. After local food injection, we identified 40 genes with a potential role in the early immune response to food allergens (most notably CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3). These 40 genes were enriched in processes related to immune activation, such as the acute-phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18 (also called GITRL), a member of the TNF superfamily that is best studied for its costimulatory effect on T cells, was the most dysregulated early EoE gene, showing a 12-fold increase compared with baseline and an 18-fold increase compared with a negative visual response. Further experiments showed that the esophageal epithelium may be an important source of TNFSF18 in EoE, which was rapidly induced by costimulating esophageal epithelial cells with the EoE-relevant cytokines IL-13 and TNF-α., Conclusions: Our data provide unprecedented insight into the transcriptomic changes that mediate the acute mucosal immune response to food allergens in EoE and suggest that TNFSF18 may be an important effector molecule in this response., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response., Aim: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients., Methods: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks., Results: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p < .05), while calcium (p = .058) and full-fat cheese/curd (p = .056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p < .05), while ultra-processed meals (p = .059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p = .058)., Conclusion: Dietary composition may be related to inflammation in adult EoE patients. High-quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objective: We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study., Methods: Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API ('GRS+API', composite endpoint) and for GRS and API separately., Results: 202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081)., Conclusions: Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS., Trial Registration Number: The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465)., Competing Interests: Competing interests: GB is an Editorial Board Member of Gut., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC., Design: Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup., Results: Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC., Conclusion: Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC., Trial Registration Number: NCT03633617., Competing Interests: Competing interests: AJB: Dr Falk Pharma, Norgine, Nutricia, Sanofi, SST and Thelial—research funding; Alimentiv, Aqilion, AstraZeneca, Dr Falk Pharma, Laborie, Medtronic, Regeneron Pharmaceuticals and Sanofi—consulting fees. ED: Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Celgene/Receptos/BMS, GSK, Meritage, Miraca, Nutricia, Regeneron Pharmaceuticals, Revolo and Shire/Takeda—research funding; Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, Gossamer Bio, GSK, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron Pharmaceuticals, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE and Upstream Bio—consulting fees; Allakos, Holoclara and Invea—educational funding. IH: Allakos, AstraZeneca, Calyx/Parexel, Eli Lilly, Ellodi/Adare, EsoCap, Gossamer Bio, Nexstone, Pfizer/Arena, Phathom, Receptos/BMS, Sanofi/Regeneron Pharmaceuticals and Shire/Takeda—consulting fees; Allakos, AstraZeneca, Ellodi/Adare, Pfizer/Arena, Receptos/BMS, Regeneron Pharmaceuticals and Shire/Takeda—research funding; Sanofi/Regeneron Pharmaceuticals—speaker fees. AJL: Dr Falk Pharma and EsoCap—consulting fees; Dr Falk Pharma, Ellodi and Regeneron Pharmaceuticals—research funding. CS: Adare Pharmaceuticals, AstraZeneca, Calypso, EsoCap, Dr Falk Pharma, GmbH and Regeneron Pharmaceuticals—consulting fees. AS, EM, JM and XS: employees of Regeneron Pharmaceuticals and may hold stock and/or stock options in the company. EL, LG and LM: employees of Sanofi and may hold stock and/or stock options in the company., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events., Methods: We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring., Results: A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo ( P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events ( P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment ( P = 0.042)., Conclusions: We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies.

Goals: Develop quality indicators for ineffective esophageal motility (IEM)., Background: IEM is identified in up to 20% of patients undergoing esophageal high-resolution manometry (HRM) based on the Chicago Classification. The clinical significance of this pattern is not established and management remains challenging., Study: Using RAND/University of California, Los Angeles Appropriateness Methods, we employed a modified-Delphi approach for quality indicator statement development. Quality indicators were proposed based on prior literature. Experts independently and blindly scored proposed quality statements on importance, scientific acceptability, usability, and feasibility in a 3-round iterative process., Results: All 10 of the invited esophageal experts in the management of esophageal diseases invited to participate rated 12 proposed quality indicator statements. In round 1, 7 quality indicators were rated with mixed agreement, on the majority of categories. Statements were modified based on panel suggestion, modified further following round 2's virtual discussion, and in round 3 voting identified 2 quality indicators with comprehensive agreement, 4 with partial agreement, and 1 without any agreement. The panel agreed on the concept of determining if IEM is clinically relevant to the patient's presentation and managing gastroesophageal reflux disease rather than the IEM pattern; they disagreed in all 4 domains on the use of promotility agents in IEM; and had mixed agreement on the value of a finding of IEM during anti-reflux surgical planning., Conclusion: Using a robust methodology, 2 IEM quality indicators were identified. These quality indicators can track performance when physicians identify this manometric pattern on HRM. This study further highlights the challenges met with IEM and the need for additional research to better understand the clinical importance of this manometric pattern., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite deprescribing initiatives to curb overutilization of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge., Summary: An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction., Key Messages: Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. When commencing a PPI, patients should understand the reason for treatment, planned duration, and review date. PPI use at hospital discharge should not be continued without a recognized indication for long-term treatment. Long-term PPI therapy should be reviewed at least annually. PPI use-reduction should be based on the lack of a rational indication for long-term PPI use, not concern for PPI-associated adverse events. PPI use-reduction strategies involving switching to on-demand PPI or dose tapering, with rescue therapy for rebound symptoms, are more likely to succeed than abrupt cessation., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Patients with reflux-like symptoms (heartburn and regurgitation) are often not well advised on implementing individualised strategies to help control their symptoms using dietary changes, lifestyle modifications, behavioural changes or fast-acting rescue therapies. One reason for this may be the lack of emphasis in management guidelines owing to 'low-quality' evidence and a paucity of interventional studies. Thus, a panel of 11 gastroenterologists and primary care doctors used the Delphi method to develop consolidated advice for patients based on expert consensus. A steering committee selected topics for literature searches using the PubMed database, and a modified Delphi process including two online meetings and two rounds of voting was conducted to generate consensus statements based on prespecified criteria (67% voting 'strongly agree' or 'agree with minor reservation'). After expert discussion and two rounds of voting, 21 consensus statements were generated, and assigned strength of evidence and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) rating. Eleven statements achieved the strongest (100%) agreement: five are related to diet and include identification and avoidance of dietary triggers, limiting alcohol, coffee and carbonated beverages, and advising patients troubled by postprandial symptoms not to overeat; the remaining six statements concern advice around smoking cessation, weight loss, raising the head-of-the-bed, avoiding recumbency after meals, stress reduction and alginate use. The aim of developing the consensus statements is that they may serve as a foundation for tools and advice that can routinely help patients with reflux-like symptoms better understand the causes of their symptoms and manage their individual risk factors and triggers., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs., Methods: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment., Results: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed., Conclusion: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To determine the efficacy and safety of cola in resolving complete oesophageal food bolus impaction., Design: Open label, multicentre, randomised controlled trial., Setting: Emergency departments of five Dutch hospitals at the secondary and tertiary level, between 22 December 2019 and 16 June 2022., Participants: 51 adults presenting with complete oesophageal food bolus impaction, defined as a sudden inability to pass saliva after consumption of foods. Patients who ingested meat that contained bones, and patients with an American Society of Anesthesiologists (ASA) physical status classification of IV or higher were excluded., Interventions: 28 patients in the intervention group were instructed to consume 25 mL cups of cola at intervals up to a maximum total volume of 200 mL. 23 patients in the control group awaited spontaneous passage. In either group, if complete resolution of symptoms did not occur, endoscopic removal was performed following current guidelines: within 6 hours for patients with complete obstruction, and within 24 hours for partial obstruction. In case of complete resolution of symptoms, elective diagnostic endoscopy was required., Main Outcome Measures: Improvement of oesophageal food bolus obstruction as reported by patients (ie, aggregate of complete and partial passage), and evaluation of complete passage. The secondary outcome was any intervention related adverse event., Results: Cola did not have a meaningful effect on the improvement of food bolus obstruction (17/28 (61%) intervention v 14/23 (61%) control; odds ratio 1.00, 95% confidence interval 0.33 to 3.1; relative risk reduction 0.0, 95% confidence interval -0.55 to 0.36; P>0.99). Complete passage was reported more often in the intervention group but this difference was not significant (12/28 (43%) intervention v 8/23 (35%) control; odds ratio 1.4 (0.45 to 4.4); relative risk reduction -0.23 (-1.5 to 0.39); P=0.58). No severe adverse events occurred. However, six (21%) patients in the intervention group experienced temporary discomfort after drinking cola., Conclusions: In this study, cola consumption did not lead to a higher rate of improvement of complete oesophageal food bolus impaction. Given the lack of adverse events in the treatment group and some events of resolution after treatment, cola might be considered as a first line treatment, but should not delay any planning of endoscopic management., Trial Registration: Netherlands Trial Register (currently International Clinical Trial Registry Platform) NL8312., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Netherlands Organisation for Scientific Research NWO for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)