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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

A pilot study was conducted to evaluate the association between gastroesophageal reflux disease (GERD) and obstructive sleep apnea syndrome (OSAS) using pH-impedance monitoring and polysomnography. The study found a direct association between higher apnea hypopnea index (AHI) values and various pH-impedance monitoring metrics in the recumbent position, suggesting that nocturnal reflux events may exacerbate the occurrence of apneas. However, no significant association was found in the upright position or overall exam. The results suggest that the management of one condition could positively influence the other, and further research is needed to fully understand this relationship. [Extracted from the article]

Background and Aim: Suboptimal disease control (SDC) and its contributing factors in IBD according to STRIDE-II criteria is unclear. IBD-PODCAST was a non-interventional, international, multicenter real-world study to assess this., Methods: Data from the Italian IBD cohort (N=220) are presented here. Participants aged ≥19 with confirmed IBD diagnosis of ≥1 year were consecutively enrolled. A retrospective chart review and cross-sectional assessment by physicians and patients within the past 12 months were performed. SDC or optimal disease control was assessed using adapted STRIDE-II criteria., Results: At the index date, 53.4 % of 116 CD patients and 49.0 % of 104 UC patients had SDC, mainly attributed to a Short Inflammatory Bowel Disease Questionnaire score <50, failure to achieve endoscopic remission, and the presence of active extra-intestinal manifestations in both diseases. Disease monitoring with imaging and/or endoscopy during the previous year was conducted in ∼50 % of patients, with endoscopy performed in ∼40 %. Potential therapeutic adjustments were reported for half of the patients., Conclusions: This study highlights SDC in a significant portion of IBD Italian patients. These results emphasize the need for more proactive management strategies in both CD and UC patients., Competing Interests: Competing interests, (Copyright © 2024. Published by Elsevier Ltd.)

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.)

Objective: Ulcerative colitis and Crohn's disease are chronic inflammatory diseases and represent the two most important types of inflammatory bowel diseases (IBD), while spondyloarthritis (SpA) comprises a heterogeneous group of systemic inflammatory chronic rheumatic diseases, including peripheral SpA and axial SpA. Joint manifestations are the most commonly observed extraintestinal manifestations, and they can precede or not the diagnosis of IBD. Notably, in women, misdiagnoses of IBD as irritable bowel syndrome and SpA as fibromyalgia are common, leading to delayed diagnoses, increased disease burden, and poorer prognoses. This narrative review emphasizes the critical role of diagnostic tools in facilitating early referrals of IBD patients with suspected SpA and vice versa to rheumatologists and gastroenterologists, respectively. Special attention is given to the multidisciplinary approach for more effective management of these conditions, particularly in female patients., Methods: In this narrative review, we critically evaluated the literature on this topic, focusing on papers written in English that address female issues in IBD and SpA., Results: IBD and SpA are chronic inflammatory disorders often occurring in the same patients. Female patients are often misdiagnosed, and this delay in diagnosis is associated with a higher disease burden and a poorer prognosis., Conclusions: A multidisciplinary approach is needed to enable early referral between gastroenterologists and rheumatologists, as this means a better prognosis for patients with a reduction in the economic and social burden associated with IBD and SpA.

Background: Age-related changes in the gastrointestinal system are common and may be influenced by physiological aging processes. To date, a comprehensive analysis of esophageal motor disorders in patients belonging to various age groups has not been adequately reported., Methods: We conducted a retrospective assessment of high-resolution manometry (HRM) studies in a multicenter setting. HRM parameters were evaluated according to the Chicago Classification version 4.0. Epidemiological, demographic, clinical data, and main manometric parameters, were collected at the time of the examination. Age groups were categorized as early adulthood (<35 years), early middle-age (35-49 years), late middle-age (50-64 years), and late adulthood (≥65 years)., Results: Overall, 1341 patients (632, 47.0% male) were included with a median age of 55 years. Late adulthood patients reported more frequently dysphagia (35.2%) than early adulthood patients (24.0%, p = 0.035), early middle-age patients (21.0%, p < 0.0001), and late middle-aged patients (22.7%, p < 0.0001). Esophagogastric junction outflow obstruction was more prevalent in late adulthood (16.7%) than in early adulthood (6.1%, p = 0.003), and in early middle-age (8.1%, p = 0.001). Patients with normal esophageal motility were significantly younger (52.0 years) than patients with hypercontractile esophagus (61.5 years), type III achalasia (59.6 years), esophagogastric junction outflow obstruction (59.4 years), absent contractility (57.2 years), and distal esophageal spasm (57.0 years), in multivariate model (p < 0.0001)., Conclusion: The rate of esophageal motor disorders is higher in older patients, in particular esophagogastric junction outflow obstruction and hypercontractile esophagus. Future prospective studies are necessary to confirm our results and to find tailored strategies to improve clinical outcomes., (© 2024 The American Geriatrics Society.)

Competing Interests: Conflict of interest The authors declare no conflict of interest.

Peroral endoscopic myotomy (POEM) is an established treatment for achalasia, yet there is still a lack of technical standardization. No clear definition of 'long', 'standard', or 'short' POEM exists to date. We conducted a systematic review with meta-analysis to analyze current POEM length standards. We included studies reporting technical details of POEM, in which no definite or comparative myotomy length was intentionally adopted (standard myotomy). The primary outcome was the pooled mean total myotomy length. Sub-group analyses were performed to explore heterogeneity across studies. From the initial 7172 records, 31 studies with 3023 patients were included. Pooled mean of total myotomy length was 10.39 cm (95% CI 10.06-10.71; I2 99.3%). Pooled mean of esophageal and gastric myotomy length, provided by 17 studies, was 7.11 cm (95% CI 6.51-7.71; I2 99.8%) and 2.81 cm (95% CI 2.41-3-22; I2 99.8%), respectively. On subgroup analysis for achalasia subtypes, pooled mean length in non-spastic achalasia (type I and II) was 10.17 cm (95% CI 9.91-10.43; I2 94.2%), while in type III it was 14.02 cm (95% CI 10.59-17.44; I2 98.9%). Pooled mean myotomy length for studies conducted between 2014-2020 was 10.53 cm (95% CI, 10.22-10.84; I2 99.1%) and 9.74 cm (95% CI, 7.95-11.54; I2 99.7%) in 2021-2022. Myotomy length during a 'standard' POEM is 10.4 cm, remaining over 10 cm in non-spastic achalasia. The high heterogeneity across studies confirms that the POEM technique needs further standardization. We found no significant time trend towards adopting short POEM, despite recent evidence supporting its use., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Introduction: Proton pump inhibitors (PPIs) are the first-line treatment for gastroesophageal reflux disease (GERD). However, due to their intrinsic limitations, there are still unmet clinical needs that have fostered the development of potassium-competitive acid blockers (p-CABs). Currently, four different drugs (vonoprazan, tegoprazan, fexuprazan, keverprazan) are marketed in some Asian countries, whereas only vonoprazan and tegoprazan are available in Western countries (U.S.A. and Brazil or Mexico, respectively)., Areas Covered: This review summarizes the current knowledge on p-CABs acute and long-term safety in GERD treatment compared to that of PPIs. Full-text articles and abstracts were searched in PubMed., Expert Opinion: p-CABs proved to address some of the unmet clinical needs in GERD, with a favorable risk-benefit ratio compared to conventional PPIs. Preclinical and clinical findings have highlighted p-CAB safety to be superimposable, to that of PPIs, in short-term treatments, although further studies are warranted to monitor their effects in long-term therapy. From an epidemiological point of view, the paucity of rigorous data for many variables (e.g. age, ethnicity, drug interactions, comorbidities, genetic polymorphisms, interindividual susceptibility, microbial dysbiosis) deserves a worldwide framework of continuous pre/post-marketing pharmacovigilance programs to reduce potential confounding factors and accurately link acute and chronic p-CAB therapy to adverse outcomes.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed.  A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001).    Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment., (© 2024. The Author(s).)

Introduction: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics., Methods: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints., Results: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00)., Discussion: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

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.)

Introduction: This study proposes a revised version of the Reflux Symptom Index (R-RSI), a seventeen-item questionnaire that was revised to increase the suspicion of laryngopharyngeal reflux disease (LPRD)., Methods: Internal validation involved 213 participants, comprising 160 subjects without a previous LPRD diagnosis and 53 subjects with a self-reported previous diagnosis of LPRD with or without gastroesophageal reflux disease (GERD). Test-retest reliability and internal consistency were calculated. For the external validation, 56 patients (independent from the previous cohort) were enrolled to explore the R-RSI screening properties and determine a cutoff using 24-h MII-pH as the gold standard., Results: R-RSI test-retest reliability was high, both for the total score (ICC: 0.970) and for each item (ranging from 0.876 to 0.980). Cronbach's alpha was 0.910, indicating excellent internal consistency of the questionnaire. Participants with a previous self-reported diagnosis scored significantly higher (mean 24.94 ± 7.4; median 26, IQR 20-29) than those without a previous diagnosis (mean 4.66 ± 5.3; median 4, IQR 1-6) (p value &lt;0.0001). Participants with both previous LPRD and GERD diagnoses had higher scores (27.20 ± 7.8) compared to those with only LPRD (21.77 ± 5.5) (p value = 0.003). Using 24-h MII-pH diagnosis as a gold standard, the optimal R-RSI cutoff point was determined to be 18, with a sensitivity of 84.5% and a specificity of 81.8%, positive predictive value of 95%, and negative predictive value of 60%., Conclusions: Our results suggest that the R-RSI may be useful to suspect LPRD, with or without GERD. The R-RSI is a self-administered patient-reported outcome questionnaire that demonstrates excellent reliability and high screening properties. Employing a cutoff of ≥18 in the R-RSI can assist in diagnosing and monitoring LPRD., (© 2024 S. Karger AG, Basel.)

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.

Introduction: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG)., Methods: This was a retrospective, longitudinal, multicenter study conducted at 8 Italian tertiary referral centers. We retrieved clinical data from all histologically proven patients with AIG. Differences between Helicobacter pylori -exposed vs H. pylori -naive and anti-parietal cell antibody (PCA)-positive vs PCA-negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated with gNEN was fitted., Results: A total of 1,598 patients with AIG (median age 58 years, interquartile range 46-68; F:M ratio 2.7:1) were included. H. pylori -naive patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; P = 0.012), type 1 diabetes mellitus (4.9% vs 2.3%; P = 0.025), and pernicious anemia (30.9% vs 21.1%; P = 0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; P < 0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; P < 0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% confidence interval [CI] 0.07-0.20) and 1.22 (95% CI 1.03-1.42) per 100 person/year, respectively. Having a vitamin B12/iron deficiency manifestation at AIG diagnosis was associated with a 16.44 (95% CI 9.94-27.20 P < 0.001) hazard ratio of gNEN., Discussion: The "pure" AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori . In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection., (Copyright © 2024 by The American College of Gastroenterology.)

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 pathophysiological and clinical value of performing High-Resolution Manometry (HRM) after laparoscopic fundoplication (LF) for gastroesophageal reflux disease (GERD) is still unclear and debated., Objective: We sought to establish the HRM parameters indicative of functioning fundoplications, and whether HRM could distinguish them from tight or defective ones., Methods: The study involved patients with GERD who underwent laparoscopic Nissen (LN) or Toupet (LT) fundoplication between 2010 and 2022. HRM and 24-h pH monitoring were performed before and 6 months after surgery. The study population was divided into 5 groups: LN and LT patients with normal 24h-pH findings (LNpH- and LTpH-, respectively); LN and LT patients with pathological 24h-pH findings (LNpH+ and LTpH + groups, respectively); and patients with a postoperative dysphagia intensity score >2 (Dysphagia group). The novel Hiatal Morphology (HM) classification was applied, envisaging 3 different subtypes: HM1 (normal), HM2 (intrathoracic fundoplication), and HM3 (slipped fundoplication)., Results: Among the 132 patients recruited during the study period, 46 were in the LNpH- group, 51 in the LTpH- group, 15 in the LNpH + group, 7 in the LTpH + group, and 5 in the Dysphagia group. In multivariate analysis, postoperative abdominal lower esophageal sphincter length (p = 0.001) and HM2 (p < 0.001) were both independently associated with surgical failure. Integrated relaxation pressure was significantly higher in the Dysphagia group than in the LNpH- group., Conclusion: This study generated reference HRM values for an effective LF, and confirms that using HRM to assess the neo-sphincter and HM improves the clinical assessment in cases of symptom recurrence., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis., Materials and Methods: This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed., Results: Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn's disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis., Conclusions: Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed., Methods: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events., Results: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q 1 -q 3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11)., Conclusions: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

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.)

Gastrointestinal manifestations are common across all hereditary transthyretin amyloidosis (ATTRv) genotypes. However, they are poorly specific, and their recognition as part of ATTRv is difficult, resulting in misdiagnosis with more common conditions. Moreover, delays in diagnosis occur because of fragmented knowledge, a shortage of centers of excellence and specialists dedicated to ATTRv management, and the scarce involvement of gastroenterologists in multidisciplinary teams. A group of Italian gastroenterologists with experience in the management of ATTRv took part in a project aimed at assessing the awareness of ATTRv among the community of Italian gastroenterologists through an online survey and providing education about practical aspects of ATTRv management. Survey results reported low participation, and very few patients with ATTRv were cared for by gastroenterologists. This highlights the need for greater attention to rare diseases in gastroenterology and emphasizes increasing awareness of ATTRv and diagnostic suspicion. Based on the experts' recommendations, a diagnosis of ATTRv should be suspected when at least one of the 'red flags' is detected. Subsequently, it is suggested to promptly ask for genetic testing and exclude a serum and urinary monoclonal protein, even before the detection of amyloid in biopsy samples, particularly in non-endemic areas., Competing Interests: Conflict of interest M.C. has served as an invited speaker and advisory board member for Alnylam, Takeda, Janssen, Biogen, Pfizer, and Galapagos. L.O. has received consultation and speaker fees from Alnylam, Pfizer, Astra Zeneca, Novo Nordisk, BridgeBio and SOBI; M.B. has served as an invited speaker for Aboca, Alnylam, Alfasigma, Diadema, Agave, GE Healthcare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eosinophilic colitis (EC) is the rarest among primary eosinophilic gastrointestinal disorders (EGID). EC is underdiagnosed due to its blurred and proteiform clinical manifestations. To explore the clinical and atopic characteristic of EC adult patients, the diagnostic delay, and relapse-associated factors, by comparison with patients with eosinophilic esophagitis (EoE) and irritable bowel syndrome (IBS). EC patients followed-up at four clinics were included, and clinical, histopathological, and laboratory data were retrieved. As control groups, age-matched patients with EoE and IBS were recruited. Allergy tests included skin prick test and serum specific IgE. Diagnostic delay was assessed. Overall, data from 73 patients were retrieved, including 40 with EC (median age 39 years IQR 22.5-59, F:M 2.1:1), 12 with EoE (F:M ratio: 1:5), and 21 with IBS (F:M ratio: 1:0.9). The most common features in EC patients were female sex (67.5%), atopy (77.5%), abdominal pain/distention (70%), diarrhoea (77.5%), and faecal calprotectin elevation (22.5%). Blood eosinophils were elevated in EoE, but not in EC (p < 0.001), while ECP did not differ across the three groups (p = 0.4). The frequency of allergen sensitization reached 25% of patients. Several frequent pan-allergens for this region were present. The overall diagnostic delay was 10 months (IQR 4-15). Factors contributing to a greater diagnostic delay were atopy, weight loss, and a previous misdiagnosis. EC is mostly a diagnosis of exclusion, burdened by a substantial diagnostic delay. In female patients the presence of allergen sensitization, abdominal symptoms and faecal calprotectin elevation should raise the suspicion of EC., (© 2024. The Author(s).)

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.)

Background: Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs., Objectives: To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities., Design: An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient's association (ESEO Italia), to enrich the study findings., Data Sources and Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease's landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps., Results: The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise., Conclusion: Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways., Competing Interests: E.S. 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, Takeda, and Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, and Zeta Farmaceutici. G.B. received consulting fees for analysis, conduction, and/or participation in Advisory Boards and/or Conferences from Aboca, AB Biotics, Agave, Alfasigma, AG Pharma, Bayer, Bromatech, Cadigroup, Biocodex, Sanofy, GE Healthcare, Mayoly, Diadema, and Sofar. M.B.B. received fees for lectures from ALK, Astra, Chiesi, GSK, and Sanofi. Nicola De Bortoli received consulting fee from Sofar, Reckitt-Benkiser, Dr. Falk, Malesci, Alfasigma, and Sanofi Genzyme; and for the participation to Advisory Board: Astra Zeneca, Dr. Falk. A.D.S. no conflict of interest to declare. S.O. received consulting fees from Sanofi, Alfasigma, Medtronic, and Bristol Myers Squibb. R.P. received consulting fees from Dr Falk Pharma and Sanofi for analysis conduction, or for the participation in Advisory Boards and/or Conferences. F.R. received consulting fees from Sanofi, Dr. Falk, GSK (Advisory Boards and Conferences). A.T. no conflict of interest to declare. F.R. no conflict of interest to declare. A.C. no conflict of interest to declare., (© The Author(s), 2024.)

Background: Inflammatory bowel diseases (IBDs) have a peak incidence between the second and fourth decades of life and can affect women's reproductive life., Objectives: Our study aimed to assess the impact of IBD on the reproductive life of female patients with this condition., Design: Cross-sectional study., Methods: Women with IBD followed at our IBD Unit and a group of healthy controls were enrolled. Data on reproductive life were collected using a dedicated questionnaire., Results: The study included 457 women, of whom 228 had IBD, and 229 age-matched healthy controls. No differences were found in the use of contraceptives, infertility, and endometriosis. The risk of spontaneous and voluntary abortions was significantly higher in IBD patients than in healthy controls [odds ratio (OR) 2 and 3.62, respectively]. The risk of obstetrical complications in the IBD population was more than six times higher in patients who experienced disease reactivations during pregnancy than in those with persistent remission [OR 6.9, 95% confidence interval (CI) 1.51-31.28]. Finally, we found that the chances of breastfeeding were 66% lower in patients with IBD than in controls (OR 0.44, 95% CI 0.22-0.91)., Conclusion: Our study underlines the negative impact of IBD on women's reproductive life, supporting the need for proactive preconception counseling., Competing Interests: The Associate Editor of Therapeutic Advances in Gastroenterology, Edoardo Vincenzo Savarino, is an author of this paper, therefore, the peer review process was managed by alternative members of the Board and the submitting Editor was not involved in the decision-making process. AB (Alessandro Borsato), DM (Daria Maniero), FDL (Francesco della Loggia), GL (Greta Lorenzon), AZ (Annalisa Zanini) and CC (Cristina Canova) have nothing to declare. FZ (Fabiana Zingone) has served as a speaker for EG Stada Group, Fresenius Kabi, Janssen, Pfizer, Takeda, Unifarco, Malesci, Kedrion, Abbvie; has served as a consultant for Galapagos and Takeda BB (Brigida Barberio) has served as speaker for Alfasigma, Janssen, MSD, Procise, Sofar, Takeda; has served as a consultant for Doxapharma, EVS (Edoardo Vincenzo Savarino) has served as speaker for Abbvie, AGPharma, Alfasigma, Dr. Falk, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Unifarco; EVS has served as a consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fresenius Kabi, Janssen, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; EVS received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco., (© The Author(s), 2024.)

Background: Achalasia is a rare disorder characterized by impaired esophageal motility and symptoms like dysphagia, regurgitation, chest pain, and weight loss. A timely diagnosis is crucial to adequately manage this condition., Aims: This study aimed to assess the diagnostic delay from symptom onset to a definite diagnosis of achalasia, and to identify associated factors., Methods: This retrospective, single-center study included patients diagnosed with achalasia between January 2013 and September 2023. Demographic data, symptoms, manometric, endoscopic, and radiological findings were collected. We also considered socio-economic deprivation. Early diagnosis was defined as occurring within 12 months of symptom onset, while late diagnosis was defined as occurring more than 12 months., Results: We included 278 patients (142 males, median age 58 years). Dysphagia was the most common symptom (96 %), followed by regurgitation (70.1 %). The median diagnostic delay was 24 months (IQR 12-72, range 0-720), with 213 patients (76.6 %) experiencing late diagnosis. Early diagnosis was more common in patients with weight loss (63.1% vs. 42.0 %, p = 0.003). Lower material deprivation correlated with shorter diagnostic delay (24 months, IQR 10-60 vs. 60 months, IQR 18-300, p = 0.001)., Conclusions: Achalasia diagnosis is often delayed. Weight loss along with socio-economic factors, influence the timeliness of diagnosis. Improving awareness of disease and relevance of initial symptoms may facilitate earlier diagnosis and treatment., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aims: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC., Methods: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed., Results: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported., Conclusions: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Recent studies showed that early surgery for Crohn's disease leads to a lower recurrence rate. However, the underlying mechanism is unknown., Objective: The study aims to analyze the innate immunity microenvironment in ileal mucosa according to the duration of Crohn's disease., Design: A prospective cohort study., Settings: Tertiary referral center for IBD surgery., Patients: A total of 88 consecutive patients with Crohn's disease undergoing ileocolonic resection were prospectively enrolled. Mucosal samples were obtained from both healthy and inflamed ileum. Data from a public data set were analyzed as an external validation cohort., Main Outcome Measures: Neutrophil infiltration was evaluated by histological asessment and macrophage subpopulation was assessed by immunohistochemistry. Expressions of TLR2 , TLR4 , TLR5 , DEFB1 , DEFB4A , DEFB103 , DEFA5 , and DEFA6 were quantified by real-time quantitative polymerase chain reaction. Concentrations of BDNF, CCL-11, ICAM-1, IL-1A, IL-1β, IL-1RN, IL-12p40, IL-12p70, IL-15, IL-17A, IL-23A, MMP-3, CCL-3, KITLG, and VEGFA were determined with an immunometric assay., Results: Neutrophil infiltration is inversely correlated with disease duration. DEFB4A mRNA expression tended to be higher in late-stage Crohn's disease ( p = 0.07). A higher number of macrophages expressed CD163 at low intensity in late-stage Crohn's disease ( p = 0.04). The concentration of IL-15 ( p = 0.02) and IL-23A ( p = 0.05) was higher in healthy ileal mucosa of early-stage patients. In the external cohort, expressions of DEFB1 ( p = 0.03), DEFB4A ( p = 0.01), IL-2 ( p = 0.04), and IL-3 ( p = 0.03) increased in patients with late-stage Crohn's disease., Limitations: A relatively small number of patients, especially in the newly diagnosed group., Conclusions: In newly diagnosed Crohn's disease, high levels of IL-15 and IL-23 in healthy mucosa suggest that innate immunity is the starter of acute inflammation. Moreover, M2 macrophages increase in the healthy mucosa of patients with late-stage Crohn's disease, suggesting that reparative and profibrotic processes are predominant in the long term, and in this phase, anti-inflammatory therapy may be less efficient. See Video Abstract ., Activacin De La Inmunidad Innata En La Recientemente Diagnosticada Enfermedad De Crohn Ileoclica Un Estudio De Cohorte: ANTECEDENTES:Estudios recientes demostraron que la cirugía temprana para la enfermedad de Crohn (EC) conduce a una menor tasa de recurrencia. Sin embargo, se desconoce el mecanismo subyacente.OBJETIVO:El estudio tiene como objetivo analizar el microambiente de la inmunidad innata en la mucosa ileal según la duración de la EC.DISEÑO:Un estudio de cohorte prospectivo.AJUSTES:Centro terciario de referencia para cirugía de EII.PACIENTES:Fueron registrados de manera prospectiva y consecutiva 88 pacientes con EC sometidos a resección ileocolónica. Se obtuvieron muestras de mucosa ileal, tanto del íleon sano como del íleon inflamado. Los datos se analizaron como una cohorte de validación externa.PRINCIPALES MEDIDAS DE RESULTADO:Fueron evaluados la infiltración de neutrófilos por histología y la subpoblación de macrófagos por inmunohistoquímica. La expresión de TLR2, TLR4, TLR5, DEFB1, DEFB4A, DEFB103, DEFA5 y DEFA6 fueron cuantificados mediante qPCR en tiempo real. Las concentraciones de BDNF, CCL-11, ICAM-1, IL-1A, IL-1B, IL-1RN, IL-12 p40, IL-12 p70, IL-15, IL-17A, IL-23A, MMP-3, CCL-3, KITLG, VEGFA se determinaron con ensayo inmunométrico.RESULTADOS:La infiltración de neutrófilos se correlaciona inversamente con la duración de la enfermedad. La expresión del ARNm de DEFB4A mostro una tendencia a ser mayor en la EC en etapa tardía ( p = 0,07). Un mayor número de macrófagos expresaron CD163 a baja intensidad en la etapa tardía ( p = 0,04). La concentración de IL15 ( p = 0,02) e IL23A ( p = 0,05) fue mayor en la mucosa ileal sana de pacientes en estadio temprano. En la cohorte externa, la expresión de DEFB1 ( p = 0,03) y DEFB4A ( p = 0,01), IL2 ( p = 0,04) e IL3 ( p = 0,03) aumentó en pacientes en etapa tardía.LIMITACIONES:Un número relativamente pequeño de pacientes, especialmente en el grupo recién diagnosticado.CONCLUSIONES:En la EC recién diagnosticada, los altos niveles de IL-15 e IL-23 en la mucosa sana sugieren que la inmunidad innata es el promotor de la inflamación aguda. Además, los macrófagos M2 aumentan en la mucosa sana de pacientes con EC en etapa tardía, lo que sugiere que los procesos reparadores y profibróticos son predominantes a largo plazo y en esta fase, la terapia antiinflamatoria puede ser menos eficiente. (Traducción-Dr. Osvaldo Gauto )., (Copyright © The ASCRS 2024.)

Endoscopic treatments such as peroral endoscopic myotomy (POEM) and pneumatic dilation (PD) are commonly used to treat achalasia. Although POEM has gained popularity due to its high efficacy, the technique is more complex and may be associated with a higher risk of long-term complications compared to PD. This narrative review will focus on efficacy and safety of PD and POEM, and their suitability for different patient populations. While evidence suggests that POEM may be preferred for type III achalasia, PD remains a valuable alternative for patients with a straight, non-dilated esophagus, who prioritize the preservation of anatomical integrity and a lower risk of post-procedural gastroesophageal reflux disease (GERD). While PD carries a non negligibile risk of perforation, it has an excellent safety profile in terms of GERD and is minimally likely to cause permanent esophageal deformation. PD can be repeated with minimal risks to maintain symptom relief, whereas reversing permanent anatomical modifications related to POEM is difficult. The choice of treatment for achalasia should be patient-tailored, considering benefits and drawbacks of each intervention. The importance of personalized approach in the "POEM era" is highlighted, emphasizing the reasons why PD should still be considered a valuable option in the therapeutic armamentarium for achalasia. Areas requiring further research will be also outlined., Competing Interests: Conflict of interest Edoardo Vespa, Alberto Barchi and Sandro Passaretti have no disclosures. Silvio Danese has served as speaker and consultant for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. 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, Takeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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.)

The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications.

Background: In the last two decades the development of high-resolution manometry (HRM) has changed and revolutionized the diagnostic assessment of patients complain foregut symptoms. The role of HRM before and after antireflux procedure remains unclear, especially in surgical practice, where a clear understanding of esophageal physiology and hiatus anatomy is essential for optimal outcome of antireflux surgery (ARS). Surgeons and gastroenterologists (GIs) agree that assessing patients following antireflux procedures can be challenging. Although endoscopy and barium-swallow can reveal anatomic abnormalities, physiologic information on HRM allowing insight into the cause of eventually recurrent symptoms could be key to clinical decision making., Method: A multi-disciplinary international working group (14 surgeons and 15 GIs) collaborated to develop consensus on the role of HRM pre- and post- ARS, and to develop a postoperative classification to interpret HRM findings. The method utilized was detailed literature review to develop statements, and the RAND/University of California, Los Angeles Appropriateness Methodology (RAM) to assess agreement with the statements. Only statements with an approval rate >80% or a final ranking with a median score of 7 were accepted in the consensus. The working groups evaluated the role of HRM prior to ARS and the role of HRM following ARS., Conclusion: This international initiative developed by surgeons and GIs together, summarizes the state of our knowledge of the use of HRM pre- and post-ARS. The Padova Classification was developed to facilitate the interpretation of HRM studies of patients underwent ARS., Competing Interests: Conflicts of interest : RY: has served as a consultant for Medtronic, Ironwood Pharmaceuticals, Phathom Pharmaceuticals, StatLink MD and Medscape. RY has received research support from Ironwood Pharmaceuticals. RY has served on advisory boards for RJS Mediagnostix with stocks SM: Surgery Advisory Board for Phathom Pharmaceuticals. Consultant for Attract, Endostim, Stella , Data Monitoring and Safety Board for Biostage. JEP: has served as a consultant/speaker for Medtronic, Diversatek, Ironwood Pharmaceuticals, Phathom Pharmaceuticals, Ethicon/J&J, Endogastric Solutions, . JEP has received royalties from shared IP with Medtronic. EVS: 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, Takeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. CPG has served as a consultant for Medtronic and Diversatek AJ has an institutional consultantship agreement with Medtronic. SR: has served as consultant for Medtronic, Sanofi, Dr Falk Pharma and received research support from Medtronic and Diversatek Healthcare. JK: has served as a consultant/speaker for Allergan, Astra Zeneca, Dr Falk Pharma, Enterra, GE Healthcare, Medtronic, Mylan, Nordmark, Standard Instruments, Takeda FZ, MC, GC, LP, RS, ST: none., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Objective: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR., Methods: Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician., Results: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h., Conclusion: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR., Level of Evidence: 5 Laryngoscope, 134:1614-1624, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

(1) Background : Inflammatory bowel disease (IBD) is frequently associated to other immune-mediated inflammatory diseases (IMIDs). This study aims at assessing physicians' awareness of the issue and the current status of IMID management. (2) Methods : A web-based survey was distributed to all 567 physicians affiliated to IG-IBD. (3) Results : A total of 249 (43.9%) physicians completed the survey. Over 90% of the responding physicians were gastroenterology specialists, primarily working in public hospitals. About 51.0% of the physicians had access to an integrated outpatient clinic, where gastroenterologists collaborated with rheumatologists and 28.5% with dermatologists. However, for 36.5% of physicians, integrated ambulatory care was not feasible. Designated appointment slots for rheumatologists and dermatologists were accessible to 72.2% and 58.2% of physicians, respectively, while 20.1% had no access to designated slots. About 5.2% of physicians report investigating signs or symptoms of IMIDs only during the initial patient assessment. However, 87.9% inquired about the presence of concomitant IMIDs at the initial assessment and actively investigated any signs or symptoms during subsequent clinical examination. (4) Conclusions : While Italian physicians recognize the importance of IMIDs associated with IBD, organizational challenges impede the attainment of optimal multidisciplinary collaboration. Efforts should be directed toward enhancing practical frameworks to improve the overall management of these complex conditions.

Background: Gastroesophageal reflux disease (GERD) is a challenging condition that involves different physicians, such as general practitioners (GPs), gastroenterologists, and ears, nose and throat (ENT) specialists. A common approach consists of proton-pump inhibitors (PPIs) administration. Adjunctive pharmacological treatment may have a role in the management of non-responders to PPIs., Objectives: We aimed to survey GPs and different medical specialists to investigate the medical approaches to patients reporting GERD symptoms. In addition, we examined the use of adjunctive pharmacological treatments in patients with GERD symptoms who do not respond to PPIs., Design: Retrospective observational study., Methods: A survey was conducted among a large sample of gastroenterologists, GPs, and ENT specialists. Symptoms were divided into typical and extraesophageal, and their severity and impact on quality of life were explored with the GERD Impact Scale and with Reflux Symptom Index (RSI). All therapies administered usually for GERD were investigated., Results: A total of 6211 patients were analyzed in this survey. Patients with typical symptoms were 53.5%, while those with extraesophageal symptoms were 46.5%. The latter were more frequently reported by ENT patients (53.6%, p  < 0.0001). The GSI was higher in patients followed by gastroenterologists (9 points) and GPs (9 points) than ENT specialists (8 points), but the RSI was higher in the ENT group (14.3 ± 6.93) than in GPs and gastroenterologist groups (10.36 ± 6.36 and 10.81 ± 7.30, p  < 0.0001). Chest pain had the highest negative impact on quality of life ( p  < 0.0001). Of the 3025 patients who used PPIs, non-responders showed a lower GSI when treated with a combination of adjunctive pharmacological treatments and bioadhesive compounds, than with single-component drugs., Conclusion: Patients with GERD referred to a gastroenterologist had more severe disease and poorer quality of life. The combination of adjunctive pharmacological treatments and bioadhesive compounds seems to be effective in the management of PPI refractory patients., (© The Author(s), 2024.)

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point ( p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy ( p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.

Absent contractility (AC), a motility disorder characterized by the absence of esophageal contractions while maintaining normal lower esophageal sphincter relaxation, is recognized as a distinctive major disorder of peristalsis on esophageal high-resolution manometry that warrants comprehensive understanding. This unique motility disorder often co-occurs with connective tissue, rheumatologic or autoimmune diseases, with scleroderma being the classic example. Symptoms of gastroesophageal reflux are common. AC can profoundly impact patients' lives and result in a spectrum of complications, including erosive esophagitis, esophageal candidiasis, Barrett's esophagus, and malnutrition. To address the intricate complexities of AC and its multifaceted complications, a multidisciplinary approach is paramount. This approach considers the distinct clinical presentation and underlying rheumatologic conditions of the individual patient, recognizing the inherent diversity within this disorder. While medical management of gastroesophageal reflux remains the cornerstone of AC treatment, emerging surgical and endoscopic interventions offer additional therapeutic options for those grappling with this challenging condition. This comprehensive review provides an in-depth evaluation of recent advances in our understanding of AC and its management. It endeavors to offer valuable insights into therapeutic strategies for AC and its associated issues., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Primary sclerosing cholangitis (PSC) is a rare liver disorder characterized by biliary ducts inflammation, fibrosis and consequently chronic cholestasis, which progressively lead to liver cirrhosis. The main feature of PSC is the frequent association with inflammatory bowel disease (IBD), with an estimated prevalence of around 70% of the cases. This strong relationship seems due to the presence of shared pathogenetic mechanisms, which seem to involve the intestinal barrier function, the human gut microbiota and the immune innated and adaptative response to antigens derived from the bowel. Of relevance, PSC-IBD have specific clinical and pathological features that differ from PSC and IBD as separate entities, explaining the diversity in outcomes among these categories, and therefore the distinct clinical management that is required. The aim of this review is to present recent data regarding the epidemiology, pathobiology and clinical features of PSC-IBD.

Introduction: Systemic sclerosis (SSc) affects the connective tissue and leads to an abnormal fibrotic process in the skin and internal organs. Epidermal Growth Factor Receptor (EGFR) is able to induce cell proliferation and differentiation, and its expression is increased in SSc patients with pulmonary artery hypertension and in skin biopsies in patients with scleroderma. To date, no data on esophageal expression of EGFR are available in SSc patients. We aimed to evaluate whether the pro-fibrogenic pathways of SSc may affect EGFR expression in the esophagus., Methods: A retrospective analysis included patients with SSc and control subjects suffering from gastroesophageal reflux symptoms. Endoscopic assessment and histopathologic analyses were performed in all subjects and the presence of microscopic esophagitis was used to distinguish patients with normal esophageal mucosa and subjects with non-erosive reflux disease. EGFR expression was measured in all subjects., Results: A total of 35 patients with SSc were included, while the control group included 67 non-SSc patients. EGFR expression at the Z-line was higher in SSc patients than non-SSc patients in absence of microscopic esophagitis (median 65 %, IQR 56-71 % vs 42 %, IQR 37-54 %, p < 0.001). Microscopic esophagitis was found in 60 % of patients with SSc and 62.7 % of control patients, and EGFR expression was significantly higher in patients presenting microscopic esophagitis both in SSc and non-SSc patients., Conclusion: The EGFR hyperexpression may be due to SSc and/or reflux-related damage in patients with microscopic esophagitis. Further studies are warranted to answer open questions and provide a possible role of EGFR in terms of diagnosis, prognosis, and therapy., Competing Interests: Declaration of competing interest AP, FC, N.S., G.M., M.F., EGG, FG, EM, LM, VS, PZ: Nothing to declare. EVS has served as speaker for Abbvie, AGPharma, Alfasigma, Dr Falk, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Unifarco; EVS has served as consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fresenius Kabi, Janssen, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; EVS received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco., (Copyright © 2023 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the low FODMAP diet works is still not completely understood. These mechanisms encompass not only traditionally known factors such as luminal distension induced by gas and water but also recent evidence on the role of FOMAPs in the modulation of visceral hypersensitivity, increases in intestinal permeability, the induction of microbiota changes, and the production of short-chain fatty acids (SCFAs), as well as metabolomics and alterations in motility. Although most of the supporting evidence is of low quality, recent trials have confirmed its effectiveness, even though the majority of the evidence pertains only to the restriction phase and its effectiveness in relieving abdominal bloating and pain. This review examines potential pathophysiological mechanisms and provides an overview of the existing evidence on the effectiveness of the low FODMAP diet across various IBS subtypes. Key considerations for its use include the challenges and disadvantages associated with its practical implementation, including the need for professional guidance, variations in individual responses, concerns related to microbiota, nutritional deficiencies, the development of constipation, the necessity of excluding an eating disorder before commencing the diet, and the scarcity of long-term data. Despite its recognized efficacy in symptom management, acknowledging these limitations becomes imperative for a nuanced comprehension of the role of a low FODMAP diet in managing IBS. By investigating its potential mechanisms and evidence across IBS subtypes and addressing emerging modulations alongside limitations, this review aims to serve as a valuable resource for healthcare practitioners, researchers, and patients navigating the intricate landscape of IBS.

Pathological obesity is a growing public health concern, and its association with gastroesophageal reflux disease (GERD) poses challenges in selecting the appropriate bariatric procedure. Sleeve gastrectomy (SG) has become a popular choice due to its simplicity and effectiveness in weight loss. However, concerns regarding postoperative GERD have been raised. This study aimed to evaluate the association between preoperative assessment of esophageal function and the risk of developing postoperative GERD in patients undergoing SG. A comprehensive evaluation was conducted, including symptom assessment, upper endoscopy, high-resolution esophageal manometry (HRM), and 24 h esophageal pH impedance monitoring (MII-pH). A total of 500 obese patients were included, and their data were compared with 25 healthy volunteers. This study revealed that patients without GERD symptoms, normal endoscopy, HRM, and MII-pH were suitable candidates for SG, with low risk of developing postoperative GERD. The addition of fundoplication techniques to SG may be considered in patients with mild reflux or those at risk of developing it. This study emphasizes the importance of preoperative evaluation in selecting the appropriate bariatric procedure to minimize the risk of postoperative GERD and expand the indications for SG in obese patients.

Introduction: Immune-related adverse events (irAEs) constitute a challenge in the clinical management of solid tumors. This study aims to collect real-world data on the occurrence of immune-mediated diarrhea and colitis (IMDC) in advanced non-small cell lung cancer (aNSCLC) treated with immune checkpoint inhibitors (ICIs) and to assess the clinical impact of a multidisciplinary approach (MDA) on IMDC management., Methods: We retrospectively collected data on patients with aNSCLC consecutively treated with ICIs, either as single agent or in combination with chemotherapy, between September 2013 and July 2022. Among patients developing IMDC, we conducted blinded revision of colonic biopsies and evaluated the clinical impact of the introduction of MDA through predefined indicators., Results: Among the 607 patients included, 84 (13.8%) experienced IMDC. Pathological review highlighted a high prevalence of microscopic colitis (28%), with a collagenous pattern linked to longer symptoms duration (P = .01). IMDC occurred more frequently in females (P = .05) and PD-L1 expressors (P = .014) and was correlated with longer progression-free survival (17.0 vs 5.8, P < .001) and overall survival (28.3 vs 9.5, P < .001). The introduction of MDA was associated with increased employment of diagnostical tools such as fecal calprotectin test (P < .001), colonoscopy (P < .001), and gastroenterological evaluation (P = .017) and a significant decrease in both grade 3 conversion rate (P = .046) and recurrence after rechallenge (P = .016). Hospitalization rate dropped from 17.2% to 3.8% (P: ns)., Conclusion: These findings highlight the clinical relevance of IMDC and support the incorporation of a MDA to optimize the clinical management of this irAE to improve patient care. Prospective validation has been planned., (© The Author(s) 2023. Published by Oxford University Press.)

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.)