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Pierfrancesco Visaggi,1,* Matteo Ghisa,2,* Edoardo Vespa,3 Alberto Barchi,3 Amir Mari,4 Andrea Pasta,5 Elisa Marabotto,5,6 Nicola de Bortoli,1 Edoardo Vincenzo Savarino2 1Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 2Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; 3Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, 20132, Italy; 4Gastroenterology Unit, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel; 5Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; 6IRCCS Policlinico San Martino, Genoa, Italy*These authors contributed equally to this workCorrespondence: Edoardo Vincenzo Savarino, Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua, 35128, Italy, Tel +39-049-8217749, Email edoardo.savarino@unipd.itAbstract: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammation-mediated disease characterized by an eosinophil-predominant inflammation of the esophagus and symptoms of esophageal dysfunction. Relevant treatment outcomes in the setting of EoE include the improvement of histology, symptoms, and endoscopy findings, quality of life (QoL), and the psychological burden of the disease. Established validated tools for the assessment of EoE include questionnaires on dysphagia and QoL (ie, DSQ, EEsAI, and EoE-IQ). More recently, esophageal symptom-specific anxiety and hypervigilance, assessed using the esophageal hypervigilance and anxiety scale (EHAS), have emerged as contributors to disease burden, confirming the importance of psychological aspects in EoE patients. The EoE endoscopic reference score (EREFS) is the only validated endoscopy score in EoE and can quantify mucosal disease burden. However, esophageal panometry using the functional lumen imaging probe (FLIP) and high-resolution manometry (HRM) have shown potential to optimize the assessment of fibrostenotic features of EoE, providing novel insights into the pathophysiology of symptoms. There is a growing number of licenced and off-label therapeutic options in EoE, with various randomized controlled trials demonstrating the efficacy of proton pump inhibitors, topical steroids, food elimination diets, biological drugs, and esophageal dilatation. However, standardized optimal management strategies of EoE are currently lacking. In this review, we provide an overview of established and novel assessment tools in EoE including patient reported outcomes, FLIP panometry, HRM, endoscopy, and histology outcome measures to improve the outcomes of EoE patients. In addition, we summarize available therapeutic options for EoE based on the most recent evidence.Keywords: eosinophilic esophagitis, treatment, monitoring

Introduction: Lymphocytic esophagitis (LyE) and eosinophilic esophagitis (EoE) are immune-mediated esophageal diseases. Clinical characteristics, endoscopic findings, and treatment outcomes of LyE were compared with EoE., Methods: This was an international retrospective study on adults enrolled at 3 centers in Europe. We recorded clinical characteristics and endoscopy findings at baseline and symptoms, histology, and endoscopy outcomes after treatment of patients with LyE and EoE., Results: Demographics, clinical presentation, comorbidities, and endoscopy findings were largely different in 35 patients with LyE compared with 59 patients with EoE. Proton pump inhibitor response was generally lower in LyE., Discussion: LyE is clinically different from EoE, but differences in treatment response need further investigation., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Gastroesophageal reflux disease (GERD) is a common debilitating chronic disease presenting in two main forms based on esophageal mucosal appearance, the erosive reflux disease (ERD) and the non-erosive reflux disease (NERD). Acid secretion is a key factor in the disease pathogenesis and management. Potent acid-suppressant drugs have been manufactured since the mid of 1970s, initially with histamine-H2-receptors antagonists, and later, inhibitors of the proton pump (H+-K+-ATPase). More recently, potassium-competitive acid blockers (P-CABs), particularly Vonoprazan, have been introduced. Vonoprazan has shown high efficacy and safety profiles and exhibits several advantages that allow to overcome shortcomings of proton pump inhibitors (PPIs)., Areas Covered: In this review, we provide an updated summary of Vonoprazan pharmacodynamics and its role in clinical practice for the management of erosive esophagitis and GERD related heartburn. Moreover, we discuss characteristics of Vonoprazan that allow to bypass some limitations of the older PPIs., Expert Opinion: Long-term safety and efficacy of Vonoprazan have already been demonstrated for the induction and maintenance of ERD, preventing nocturnal acid breakthrough, reducing reflux symptoms in non-responder to standard therapy. Ongoing and future studies are expected to further elucidate its long-term benefits and potential applications in other acid-related disorders.

Introduction: Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma., Areas Covered: Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients., Expert Opinion: PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD.

Background: This study aimed to assess the distribution of esophageal inflammation in patients with eosinophilic esophagitis (EoE) and its impact on diagnosis and outcome., Aims and Methods: Data from consecutive adult EoE patients who were followed-up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected., Results: One hundred forty-nine patients were included. Proximal EoE was observed in 8.1 % of patients; distal EoE in 27.5 %; and diffuse EoE in 64.4 %. Allergic rhinitis was more prevalent in distal and diffuse than proximal EoE (72.5 % vs. 61.5 % vs 33.3 %; P = 0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was not significantly different among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were more prevalent in proximal EoE (91.7 % vs. 53.8 % distal [P = 0.01] vs. 66 % diffuse[P = 0.05]). No significant differences in fibrotic features and esophageal stenoses were observed. The clinical and histological remission rates after first-line therapy were comparable in all groups., Conclusion: Esophageal inflammation in EoE more frequently involves the entire esophagus, followed by isolated distal and proximal involvement. No clear correlation was observed between the histological extent of EoE at diagnosis and comorbidities or treatment response., Competing Interests: Declaration of competing interest Edoardo Vincenzo Savarino has served as speaker for Abbvie, Abivax, Agave, AGPharma, Alfasigma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Galapagos, Johnson&Johnson, JB Pharmaceuticals, Innovamedica/Adacyte, Eli Lilly, 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, Dr. Falk, Eli Lilly, Fenix Pharma, Johnson&Johnson, JB Pharmaceuticals, Merck & Co, Nestlè, Pfizer, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Takeda, Unifarco; he received research support from Bonollo, Difass, Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici; Nicola de Bortoli has served as speaker for: Reckitt-Benkiser, Malesci, Sofar, Dr Falk. Advisory Board: Astra-Zenecahe; the other authors have no disclosures to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Elisa Marabotto, 1 Sebastiano Ziola, 1 Vincenzo Savarino, 1 Edoardo Giovanni Giannini, 1 Manuele Furnari, 1 Giorgia Bodini, 1 Fabiana Zingone, 2 Matteo Ghisa, 2 Brigida Barberio, 2 Patrizia Zentilin, 1 Edoardo Savarino 2 1Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; 2Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, ItalyCorrespondence: Elisa MarabottoDivision of Gastroenterology, Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6, Genova 16132, ItalyTel/Fax +390103538923Email elisa.marabotto@unige.itAbstract: Potassium-competitive acid blockers (P-CABs), such as vonoprazan, represent a novel and heterogeneous class of drugs that competitively block the potassium binding site of gastric H+/K+ ATPase, thus potentially overcoming the limitations of proton-pump inhibitors. Different studies evaluated the efficacy of vonoprazan versus proton-pump inhibitors (PPIs) for the treatment of acid-related disorders, and, therefore, P-CABs present the same indications of PPIs: gastroesophageal reflux disease, gastric and duodenal ulcer healing, management of upper gastrointestinal bleeding, non-steroidal anti-inflammatory drug (NSAID)-associated ulcers and Helicobacter pylori eradication therapy. The aim of this review was to evaluate the role of vonoprazan for the treatment of peptic ulcer disease (PUD) and the management of gastric ulcer occurring after endoscopic submucosal dissection (ESD). Indeed, vonoprazan (at the dose of both 10 and 20mg) showed similar results to PPIs in patients taking long-term NSAIDs, in the absence of severe adverse effects, and provided a more rapid and effective treatment of ulcers induced by ESD. However, studies in medical literature are heterogeneous, mainly performed with a retrospective design, and often carried out in Japan only. For these reasons, further prospective, randomized studies are warranted in order to help physicians, patients, and policymakers regarding the use of vonoprazan in clinical practice.Keywords: gastric ulcer, P-CAB, adverse events, peptic disease, PPI, H2-receptor antagonists

In recent years, new translational evidence, diagnostic techniques, and innovative therapies have shed new light on esophageal achalasia and revamped the attention on this relatively rare motility disorder. This narrative review aims to highlight the most recent progress and the areas where further research is needed. The four senior authors identified five topics commonly discussed in achalasia management: i.e. pathogenesis, role of functional lumen imaging probe in the diagnostic flow chart of achalasia, how to define the outcome of achalasia treatments, how to manage persistent chest pain after the treatment, and if achalasia patients' may benefit from a regular follow-up. We searched the bibliographic databases to identify systematic reviews, meta-analyses, randomized control trials, and original research articles in English up to December 2023. We provide a summary with the most recent findings in each of the five topics and the critical points where to address future research, such as the immune-genetic patterns of achalasia that might explain the transition among the different phenotypes, the need for a validated clinical definition of treatment success, the use of neuromodulators to manage chest pain, and the need for identifying achalasia patients at risk for cancer and who may benefit of long-term follow-up. Although undoubtedly, progress has been made on the definition and management of achalasia, unmet needs remain. Debated aspects range from mechanistic insights, symptoms, objective measure relationships, and accurate clinical responses to therapeutic interventions. Translational research is eagerly awaited to answer these unresolved questions., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

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.)

Matteo Ghisa1, Carla Marinelli1, Vincenzo Savarino2, Edoardo Savarino1 1Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; 2Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, ItalyCorrespondence: Edoardo SavarinoGastrointerology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padova 351258, ItalyTel +39 049 821 7749Fax +39 049 876 0820Email edoardo.savarino@unipd.itAbstract: Gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) are two pathological conditions often strictly related, even if a clear relationship of causality has not been demonstrated. GERD is a frequent comorbidity in IPF patients, as demonstrated using combined multichannel intraluminal impedance-pH, despite being mostly clinically silent. According to that, it has been hypothesized that microaspiration of gastric material may play a fundamental role in the fibrotic transformation of pulmonary parenchyma. In contrast, it cannot be excluded that IPF may favor GERD by increasing the negative intrathoracic pressure. Therefore, this relationship is uncertain as well as not univocal. Nevertheless, the latest international guidelines recommend the use of proton pump inhibitors (PPIs) in IPF based on several data showing that PPIs can stabilize lung function, reduce disease flares and hospitalizations. On the contrary, recent studies not only question the relevance of these results, but also associate the use of PPIs with an increased risk of lung infections and a negative prognostic outcome. The aim of this review is to analyze the possible links between GERD and IPF and their possible therapeutic implications, trying to translate this scientific evidence into useful information for clinical practice.Keywords: idiopathic pulmonary fibrosis, microaspiration, chronic cough, GERD, reflux disease, motility

Background: Prokinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high-quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects., Purpose: Here, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications., (© 2024 John Wiley & Sons Ltd.)

Obesity is a chronic and multifactorial condition characterized by abnormal weight gain due to excessive adipose tissue accumulation that represents a growing worldwide challenge for public health. In addition, obese patients have an increased risk of hiatal hernia, esophageal, and gastric dysfunction, as well as gastroesophageal reflux disease, which has a prevalence over 40% in those seeking endoscopic or surgical intervention. Surgery has been demonstrated to be the most effective treatment for severe obesity in terms of long-term weight loss, comorbidities, and quality of life improvements and overall mortality decrease. The recent emergence of bariatric endoscopic techniques promises less invasive, more cost-effective, and reproducible approaches to the treatment of obesity. With the endorsement of the International Society for Diseases of the Esophagus, we started a Delphi process to develop consensus statements on the most appropriate diagnostic workup to preoperatively assess gastroesophageal function before bariatric surgical or endoscopic interventions. The Consensus Working Group comprised 11 international experts from five countries. The group consisted of gastroenterologists and surgeons with a large expertise with regard to gastroesophageal reflux disease, bariatric surgery and endoscopy, and physiology. Ten statements were selected, on the basis of the agreement level and clinical relevance, which represent an evidence and experience-based consensus of the International Society for Diseases of the Esophagus., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite increased awareness of eosinophilic esophagitis (EoE), the diagnostic delay has remained stable over the past 3 decades. There is a need to improve the diagnostic performance and optimize resources allocation in the setting of EoE., Objective: We developed and validated 2 point-of-care machine learning (ML) tools to predict a diagnosis of EoE before histology results during office visits., Methods: We conducted a multicenter study in 3 European tertiary referral centers for EoE. We built predictive ML models using retrospectively extracted clinical and esophagogastroduodenoscopy (EGDS) data collected from 273 EoE and 55 non-EoE dysphagia patients. We validated the models on an independent cohort of 93 consecutive patients with dysphagia undergoing EGDS with biopsies at 2 different centers. Models' performance was assessed by area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV). The models were integrated into a point-of-care software package., Results: The model trained on clinical data alone showed an AUC of 0.90 and a sensitivity, specificity, PPV, and NPV of 0.90, 0.75, 0.80, and 0.87, respectively, for the diagnosis of EoE in the external validation cohort. The model trained on a combination of clinical and endoscopic data showed an AUC of 0.94, and a sensitivity, specificity, PPV, and NPV of 0.94, 0.68, 0.77, and 0.91, respectively, in the external validation cohort., Conclusion: Our software-integrated models (https://webapplicationing.shinyapps.io/PointOfCare-EoE/) can be used at point-of-care to improve the diagnostic workup of EoE and optimize resources allocation., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The Lyon Consensus designates Los Angeles (LA) grade C/D esophagitis or acid exposure time (AET) >6% on impedance-pH monitoring (MII-pH) as conclusive for gastroesophageal reflux disease (GERD). We aimed to evaluate proportions with objective GERD among symptomatic patients with LA grade A, B, and C esophagitis on endoscopy., Methods: Demographics, clinical data, endoscopy findings, and objective proton-pump inhibitor response were collected from symptomatic prospectively enrolled patients from 2 referral centers. Off-therapy MII-pH parameters included AET, number of reflux episodes, mean nocturnal baseline impedance, and postreflux swallow-induced peristaltic wave index. Objective GERD evidence was compared between LA grades., Results: Of 155 patients (LA grade A: 74 patients, B: 61 patients, and C: 20 patients), demographics and presentation were similar across LA grades. AET >6% was seen in 1.4%, 52.5%, and 75%, respectively, in LA grades A, B, and C. Using additional MII-pH metrics, an additional 16.2% with LA grade A and 47.5% with LA grade B esophagitis had AET 4%-6% with low mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index; there were no additional gains using the number of reflux episodes or symptom-reflux association metrics. Compared with LA grade C (100% conclusive GERD based on endoscopic findings), 100% of LA grade B esophagitis also had objective GERD but only 17.6% with LA grade A esophagitis ( P < 0.001 compared with each). Proton-pump inhibitor response was comparable between LA grades B and C (74% and 70%, respectively) but low in LA grade A (39%, P < 0.001)., Discussion: Grade B esophagitis indicates an objective diagnosis of GERD., (Copyright © 2023 by The American College of Gastroenterology.)

Eosinophilic esophagitis (EoE) is a chronic esophageal disease that needs lifelong management and follow-up. The diagnosis requires an upper endoscopy with at least one esophageal biopsy demonstrating >15 eosinophils/high-power field, and often occurs with a diagnostic delay of up to ten years, partly due to the absence of valid non-invasive screening tools. In addition, serial upper endoscopies with esophageal biopsies are mandatory to assess the efficacy of any ongoing treatment in patients with EoE. These procedures are invasive, costly, and, when performed without sedation, are often poorly tolerated by patients. Therefore, there is the clinical need to identify reliable non-invasive or minimally invasive biomarkers that could be used to assess disease activity in clinical practice as a surrogate of peak eosinophil counts on esophageal biopsies. This review summarizes evidence on investigational non-invasive or minimally invasive biomarkers for the diagnosis and follow-up of EoE to report on the state of the art in the field and support future research. We discussed eosinophil-derived mediators including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN, also known as eosinophil protein X), eosinophil peroxidase (EPO), and major basic protein (MBP) as well as other promising non-eosinophil-derived biomarkers. Although several studies have shown the utility of most biomarkers collected from the serum, esophageal luminal secretions, and feces of EoE patients, numerous limitations currently hamper the integration of such biomarkers in clinical practice. Future studies should aim at validating the utility of non-invasive and minimally invasive biomarkers using rigorous protocols and updated consensus criteria for EoE.

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.)

Background and Aims: The optimal management of naïve and not naïve Helicobacter pylori patients remains unclear. Therefore, it is essential to evaluate whether the actual clinical practice mirrors the indications suggested by the guidelines. This study aimed to assess the effectiveness and the safety of the empirical first- and second-line treatments prescribed to patients enroled at Italian centres participating in the European Registry on H. pylori Management (Hp-EuReg)., Methods: The Hp-EuReg is an international multicentre prospective non-interventional registry starting in 2013 aiming to evaluate the management of H. pylori infection by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables assessed included demographics, previous eradication attempts, treatment regimen, effectiveness, and tolerance., Results: Overall, 3723 patients from 2013 to February 2021 were included: 2996 and 727 received an empirical first- and second-line treatment, respectively. According to the modified ITT analysis, among the first-line regimens, only the bismuth quadruple therapy with three-in-one-single capsule (BQT-TSC), the concomitant, and the sequential treatment - all lasting 10 days - achieved an eradication rate >90%. Among the second-line regimens, only the 10-day BQT-TSC reported an effectiveness >90%. High-dose PPI twice daily also significantly increased the effectiveness of some therapies. The BQT-TSC was the regimen with the highest incidence of adverse events., Conclusions: Only quadruple therapies lasting at least 10 days achieved over 90% eradication rates among the empirical first- and second-line regimens. It remains unclear whether high-dose PPI twice daily can improve the efficacy of quadruple treatment., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Eosinophilic gastrointestinal diseases (EGIDs) are chronic inflammatory disorders of the gut, including eosinophilic esophagitis (EoE), gastritis (EoG), duodenitis (EoD), gastroenteritis (EoGE), and colitis (EoC). Available treatments may be ineffective in some patients, and several clinical trials are investigating alternative treatments., Aim: We performed a systematic review of clinical trials to illustrate EGIDs treatment research trends., Methods: We searched clinicaltrials.gov to identify studies investigating EGIDs treatment. For each trial we analysed relevant data, including therapeutic intervention, method of administration, study outcomes, and temporal trends., Results: For EoE, 66 studies were eligible: 26 testing topical corticosteroids (39.4%), 17 (25.8%) monoclonal antibodies, eight (12.1%) dietary measures, five (7.6%) immunomodulators, one (1.5%) esophageal dilation, and nine (13.6%) other medical treatment strategies. With regard to EoG, EoD, and EoGE, 10 studies were testing monoclonal antibodies (71.5%), one immunomodulators (7.1%), one dietary measures (7.1%), and two other treatments (14.3%). There were no trials for EoC. Ongoing studies on corticosteroids are focused on novel delivery systems, including viscous suspensions, orally disintegrating tablets, or capsules. Increased research on monoclonal antibodies was seen from 2018, with interleukin (IL)-4 receptor-α, IL-5 receptor-α, IL-5, IL-13, IL-15, and Siglec-8 as the targets., Conclusion: Clinical trials on EGIDs are predominantly investigating corticosteroids or monoclonal antibodies. EGIDs therapeutic landscape will be trasnformed imminently., Competing Interests: Declaration of Competing Interest Pierfrancesco Visaggi: none. Matteo Ghisa: none. Brigida Barberio: none. Daria Maniero: none. Eliana Greco: none. Vincenzo Savarino: none. Christopher J Black: None. Alexander C Ford: None. Nicola de Bortoli: has received lecture or consultancy fees from Malesci and Reckitt Benckiser, outside the submitted work. Edoardo Savarino: has received lecture or consultancy fees from Abbvie, Alfasigma, Amgen, Aurora Pharma, Bristol-Myers Squibb, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Johnson&Johnson, Innovamedica, Malesci, Medtronic, Merck & Co, Reckitt Benckiser, Sandoz, Shire, SILA, Sofar, Takeda, Unifarco, outside the submitted work., (Copyright © 2022. Published by Elsevier Ltd.)

Eosinophilic esophagitis (EoE) represents a growing cause of chronic esophageal morbidity whose incidence and prevalence are increasing rapidly. The disease is characterized by eosinophilic infiltrates of the esophagus and organ dysfunction. Typical symptoms include dysphagia, chest pain, and bolus impaction, which are associated to mechanical obstructions in most patients. However, up to one in three EoE patients has no visible obstruction, suggesting that a motor disorder of the esophagus may underlie symptoms. Although potentially relevant for treatment refractoriness and symptomatic burden, esophageal dysmotility is often neglected when assessing EoE patients. The first systematic review investigating esophageal motility patterns in patients with EoE was published only recently. Accordingly, we reviewed the pathogenesis, assessment tools, manometric characteristics, and clinical implications of dysmotility in patients with EoE to highlight its clinical relevance. In summary, eosinophils can influence the amplitude of esophageal contractions via different mechanisms. The prevalence of dysmotility may increase with disease duration, possibly representing a late feature of EoE. Patients with EoE may display a wide range of motility disorders and possible disease-specific manometric pressurization patterns may be useful for raising a clinical suspicion. Intermittent dysmotility events have been found to correlate with symptoms on prolonged esophageal manometry, although high-resolution manometry studies have reported inconsistent results, possibly due to the suboptimal sensitivity of current manometry protocols. Motor abnormalities may recover following EoE treatment in a subset of patients, but invasive management of the motor disorder is required in some instances. In conclusion, esophageal motor abnormalities may have a role in eliciting symptoms, raising clinical suspicion, and influencing treatment outcome in EoE. The assessment of esophageal motility appears valuable in the EoE setting., (© 2022. The Author(s).)

Background: Eosinophilic esophagitis (EoE) is a chronic disorder of the esophagus characterized by an eosinophil-predominant inflammation and symptoms of esophageal dysfunction. Eosinophils can influence esophageal motility, leading to dysphagia worsening. The spectrum of esophageal motility in EoE is uncertain., Aim: We performed a systematic review to investigate esophageal motility in EoE., Methods: MEDLINE, EMBASE and EMBASE Classic were searched from inception to 16th November 2021. Studies reporting esophageal motility findings in EoE patients by means of conventional, prolonged, and/or high-resolution esophageal manometry were eligible., Results: Studies on esophageal conventional and high-resolution manometry (HRM) found that all types of manometric motor patterns can be found in patients with EoE and investigations on 24-hour prolonged manometry demonstrated an association between symptoms and intermittent dysmotility events, which can be missed during standard manometric analysis. Panesophageal pressurizations are the most common HRM finding and may help in formulating a clinical suspicion. Some motility abnormalities may reverse after medical treatment, while other major motility disorders like achalasia require invasive management for symptoms control. HRM metrics have demonstrated to correlate with inflammatory and fibrostenotic endoscopic features of EoE., Conclusion: Esophageal motor abnormalities are common in patients with EoE and may contribute to symptoms. The resolution of dysmotility after medical treatment corroborates that eosinophils influence esophageal motility., Competing Interests: Declaration of Competing Interest Pierfrancesco Visaggi: none. Matteo Ghisa: none. Brigida Barberio: none. Elisa Marabotto: none. Nicola de Bortoli: has received lecture or consultancy fees from Malesci and Reckitt Benckiser, outside the submitted work. Edoardo Savarino: has received lecture or consultancy fees from Abbvie, Alfasigma, Amgen, Aurora Pharma, Bristol-Myers Squibb, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Johnson&Johnson, Innovamedica, Malesci, Medtronic, Merck & Co, Reckitt Benckiser, Sandoz, Shire, SILA, Sofar, Takeda, Unifarco, outside the submitted work., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)