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Gaia Pellegatta,1 Marco Spadaccini,1 Laura Lamonaca,1 Vincenzo Craviotto,1 Ferdinando D’Amico,1 Laura Ceriotti,2 Marisa Meloni,2 Alessandro Repici1 1Humanitas Clinical and Research Center and Humanitas University, Digestive Endoscopy Unit, Division of Gastroenterology, Rozzano, MI, Italy; 2VitroScreen, Milano, ItalyCorrespondence: Gaia PellegattaDigestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Via Manzoni 56, Rozzano, MI 20089, ItalyTel +390282247091Email gaia.pellegatta@humanitas.itPurpose: New medical devices that contain hyaluronic acid (HA) and chondroitin sulphate (CS), with or without antacid components, have been developed for the treatment of gastroesophageal reflux disease (GERD) with the aim of improving oesophageal mucosal defences by creating a film on the oesophageal mucosa and acting as a mechanical barrier against the noxious components of refluxate, both acidic and basic.Methods: The film-forming and protective efficacy of medical device A based on HA and CS plus aluminium hydroxide, device B combining HA and CS with magnesium trisilicate and device C with only the combination of HA and CS was tested on a reconstructed human oesophageal epithelium (HO2E/S/5) as a biological model in 2 different pH environments, neutral and acidic, to mimic realistic conditions. Caffeine penetration kinetics and Lucifer yellow (LY) permeability modifications induced by these products were compared to those induced by a negative control series (saline solution, code NC) and positive control series (white Vaseline, code V) under neutral and acidic pH conditions.Results: Under neutral and acidic pH conditions, compared to the negative control, all the products tested reduced (> 80% and 85– 90%, respectively) the caffeine passage, and no significant difference was observed among the products tested. Under neutral and acidic conditions, the LY permeabilities registered with device A and device C were not different from that registered with the negative control, while an LY flux% increase was calculated after 2 hrs of treatment (21.1%) with device B under acidic conditions.Conclusion: These results confirm the ability of the products tested to interact with the oesophageal epithelium in order to adhere and create a stable protective film for at least 2 hours after their homogeneous distribution on the epithelium surface. Further clinical studies are needed to test these devices in the topical treatment of gastroesophageal reflux symptoms.Keywords: hyaluronic acid, chondroitin sulphate, gastroesophageal reflux disease, antacid, caffeine, Lucifer yellow

Achalasia, characterized by impaired lower esophageal sphincter (LES) relaxation and failed peristalsis, stands out as the most widely recognized primary esophageal motility disorder. It manifests with dysphagia to solid and liquid foods, chest pain, regurgitation, and weight loss, leading to significant morbidity and healthcare burden. Traditionally, surgical Heller myotomy and pneumatic dilation were the primary therapeutic approaches for achalasia. However, in 2009, Inoue and colleagues introduced a groundbreaking endoscopic technique called peroral endoscopic myotomy (POEM), revolutionizing the management of this condition. This review aims to comprehensively examine the recent advancements in the POEM technique for patients diagnosed with achalasia, delving into critical aspects, such as the tailoring of the myotomy, the prevention of intraprocedural adverse events (AEs), the evaluation of long-term outcomes, and the feasibility of retreatment in cases of therapeutic failure., Competing Interests: Declaration of competing interest Cesare Hassan: Fujifilm Co. (consultancy), Medtronic Co. (consultancy); Alessandro Repici: Fujifilm Co. (consultancy), Olympus Corp (consultancy), Medtronic Co. (consultancy); Roberta Maselli: Fujifilm Co. (consultancy). Other authors have no conflict of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/objectives: Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis., Methods: Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD., Results: The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The gender gap in the authorship of scientific research may affect career advancement. Our aim was to assess the potential gender gap in gastrointestinal (GI) journals., Methods: A systematic review was performed of the GI literature and ongoing research in the period 2020-2022. A total 10 GI journals and ongoing research on clinicaltrials.gov were selected for review. The gender gap in first and senior authorship was evaluated for each article and ongoing research project. Associations between the gender gap and possible predictors were measured and results are presented as odds ratios (ORs) with 95%CI., Results: The number of first female authors (FFAs) and senior female authors (SFAs) in published articles were 1408/4207 (33.5%) and 911/4207 (21.7%), respectively. There were 781/2654 (29.4%) female principal investigators (PI)s for the ongoing research. On comparison of non-endoscopic vs. endoscopic topics, the latter were associated with the gender gap (hepatology, OR 2.15 [95%CI 1.83-2.55]; inflammatory bowel disease, OR 2.12 [95%CI 1.60-2.45]; upper and lower GI, OR 1.31 [95%CI 1.18-1.73]); as well as the type of article (original article vs. editorial, OR 1.92 [95%CI 1.58-2.33]). The type of research was also associated with the gender gap (clinical vs. preclinical studies, OR 0.88 [95%CI 0.66-0.91])., Conclusion: Our results demonstrated a correlation between the gender gap and the design and topic of the research. Future strategies for improving equity in career development in GI endoscopy should focus on closing the gender gap in equity of authorship., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., Competing Interests: Declaration of competing interest Nicola de Bortoli: Advisory board member for: AlfaSigma, Sanofi Genzyme, Dr Falk; Lecture grants from Reckitt-Benkiser, Malesci, Dr. Flak, Sofar, Alfa-Sigma, Pharma-Line. Pierfrancesco Visaggi: Has served as speaker for Dr Falk, JB Pharmaceuticals, Malesci. Roberto Penagini: Has served as speaker for Dr Falk, Sanofi. Edda Battaglia: has served as consultant for NZP, GUNA Gaia Pellegatta has served as speaker for Dr Falk, Sanofi Genzyme, Malesci. Paola Iovino: Has served as consultant for Dr Falk Giovanni Marasco: Served as an advisory board member for AlfaSigma, EG Pharma, Monteresearch srl, Recordati, Cineca. Received lecture grants from Agave, AlfaSigma, Bromatech, Clorofilla, Echosens, Ferring, Mayoly Spindler, Menarini and Schwabe Pharma. Salvatore Oliva: Has served as speaker for Sanofi, Medtronic; Has served as consultant for: Sanofi, Medtronic, Brystol; Has received research support from Alfa Sigma, Medtronic. Francesca Racca: has served as speaker for Sanofi; has served as consultant for Dr Falk, Sanofi, GSK Erminia Ridolo: has served as consultant for Dr Falk Edoardo Vincenzo Savarino: has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Tssakeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Bruno Annibale, Federica Baiano Svizzero, Giovanni Barbara, Brigida Barberio, Ottavia Bartolo, Antonio Di Sabatino, Ludovico Docimo, Marzio Frazzoni, Manuele Furnari, Matteo Ghisa, Andrea Iori, Marco Vincenzo Lenti, Elisa Marabotto, Aurelio Mauro, Marcella Pesce, Antonino Carlo Privitera, Ilaria Puxeddu, Mentore Ribolsi, Salvatore Russo, Giovanni Sarnelli, Salvatore Tolone, Patrizia Zentilin, Fabiana Zingone: None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses., Objective: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice., Methods: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations., Results: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness., Conclusion: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Benign biliary strictures (BBS) might occur due to different pancreaticobiliary conditions. The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations. The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS, considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable. The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The endoscopic submucosal dissection (ESD) is a technically demanding and time-consuming procedure, with an increased risk of adverse events compared to standard endoscopic resection techniques. The main difficulties are related to the instability of the operating field and to the loss of traction. We aimed to evaluate in a pilot trial a new endoscopic platform [tissue retractor system (TRS); ORISE, Boston scientific Co., Marlborough, MA, USA], designed to stabilize the intraluminal space, and to provide tissue retraction and counter traction., Method: We prospectively enrolled all consecutive patients who underwent an ESD for sigmoid/rectal lesions. The primary outcome was the rate of technical feasibility. Further technical aspects such as en-bloc and R0 resection rate, number of graspers used, circumferential incision time, TRS assemblage time, submucosal dissection time, and submucosal dissection speed were provided. Clinical outcomes (recurrence rate and adverse events) were recorded as well., Results: In all, 10 patients (M/F 4/6, age: 70.4 ± 11.0 years old) were enrolled. Eight out of 10 lesions were located in the rectum. Average lesion size was 31.2 ± 2.7 mm, and mean lesion area was 1628.88 ± 205.3 mm 2 . The two sigmoid lesions were removed through standard ESD, because the platform assemblage failed after several attempts. All rectal lesions were removed in an en-bloc fashion. R0 resection was achieved in 7/8 (87.5%) patients in an average procedure time of 60.5 ± 23.3 min. None of the patients developed neither intraprocedural nor postprocedural adverse events., Conclusion: TRS-assisted ESD is a feasible option when used in the rectum, with promising result in terms of efficacy and safety outcomes. Nevertheless, our pilot study underlines few technical limitations of the present platform that need to be overcome before the system could be widely and routinely used., Competing Interests: Drs Roberta Maselli, Andrea Anderloni, Alessandro Fugazza, and Alessandro Repici received consultancy fees from Boston Scientific. Dr Silvia Carrara received in the last 36 months a research Grant from Boston Scientific on FNB Needles. No further conflict of interest to be disclosed., (© The Author(s), 2023.)

Background: Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce., Aim: To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages., Methods: Cross-sectional analysis of the EoE CONNECT registry., Results: The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood-onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p<0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p<0.001). Esophageal strictures and rings predominated in adults (p<0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p<0.001)., Conclusions: Childhood-onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment., Competing Interests: Conflict of Interest AJ Lucendo has served as a speaker, and/or has received research and/or education funding and/or consulting fees from Adare/Ellodi, Dr. Falk Pharma, Regeneron, Dr. Falk Pharma and EsoCap. C. Santander received honoraria as consultant and trainer at Laborie/MMS and Medtronic Covidien AG, and received research funding from AstraZeneca, EsoCap Biotech, Regeneron Pharmaceuticals Inc., Adare Pharmaceuticals Inc., and Dr. Falk Pharma GmbH. J. Alcedo has served as a speaker, consultant and advisory member for or has received research funding from Adare Pharmaceuticals Inc, Abbvie, MSD, Allergan, and Shire Pharmaceuticals. C Gutiérrez-Junquera has received research funding from Dr. Falk Pharma. The remaining authors have no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)