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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.We performed a systematic review of clinical trials to illustrate EGIDs treatment research trends.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.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.Clinical trials on EGIDs are predominantly investigating corticosteroids or monoclonal antibodies. EGIDs therapeutic landscape will be trasnformed imminently.

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.

Chicago classification version 4.0 (CCv4.0) introduced stringent diagnostic criteria for oesophagogastric junction outflow obstruction (EGJOO), in order to increase the clinical relevance of the diagnosis, although this has not yet been demonstrated.To determine the prevalence of EGJOO using CCv4.0 criteria in patients with CCv3.0-based EGJOO, and to assess if provocative manoeuvres can predict a conclusive CCv4.0 diagnosis of EGJOO.Clinical presentation, high resolution manometry (HRM) with rapid drink challenge (RDC), and timed barium oesophagogram (TBE) data were extracted for patients diagnosed with EGJOO as per CCv3.0 between 2018 and 2020. Patients were then re-classified according to CCv4.0 criteria, using clinically relevant symptoms (dysphagia and/or chest pain), and abnormal barium emptying at 5 min on TBE. Receiver operating characteristic (ROC) analyses identified HRM predictors of EGJOO.Of 2010 HRM studies, 144 (7.2%) fulfilled CCv3.0 criteria for EGJOO (median age 61 years, 56.9% female). Upon applying CCv4.0 criteria, EGJOO prevalence decreased to 1.2%. On ROC analysis, integrated relaxation pressure during RDC (RDC-IRP) was a significant predictor of a conclusive EGJOO diagnosis by CCv4.0 criteria (area under the curve: 96.1%). The optimal RDC-IRP threshold of 16.7 mm Hg had 87% sensitivity, 97.1% specificity, 95.7% negative predictive value and 91.3% positive predictive value for a conclusive EGJOO diagnosis; lower thresholds (10 mmHg, 12 mmHg) had better sensitivity but lower specificity.CCv4.0 criteria reduced the prevalence of EGJOO by 80%, thereby refining the diagnosis and identifying clinically relevant outflow obstruction. Elevated RDC-IRP can predict conclusive EGJOO per CCv4.0.

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.

Background/Aims: Current literature is lacking in studies comparing the incidence of adverse events (AEs) in patients with inflammatory bowel diseases (IBD) treated with adalimumab (ADA) or vedolizumab (VDZ) in a real-life scenario. Therefore, our primary aim was to compare the AEs occurring in patients taking ADA to those of patients taking VDZ. Methods: In this single center study, data on AEs from IBD patients who underwent treatment with ADA and VDZ were retrospectively collected. AE rates per 100 person-years were calculated. A Cox regression model was used to estimate the hazard ratios of the AEs between the 2 drugs. Results: A total of 16 ADA patients (17.2%) and 11 VDZ patients (7.6%) had AEs causing drug interruption during the study period (P=0.02). Most of the AEs were noninfectious extraintestinal events (50% in ADA and 54.5% in VDZ) while infections accounted for 31.2% of the AEs in patients treated with ADA and 27.3% in those treated with VDZ. The incidence rate of AEs causing withdrawal of therapy was 13.2 per 100 person-years for ADA and 5.3 per 100 person-years for VDZ, corresponding to a 76% lower risk in patients in VDZ. Considering the first year of treatment, we observed 34 subjects treated with ADA (36.5%) having at least 1 AEs and 57 (39.3%) among those taking VDZ (P=0.67). Conclusions: VDZ has a lower incidence rate of AEs causing withdrawal of treatment compared to ADA but a similar risk of AEs not causing drug interruption. Real-life head-to-head studies are still necessary to further explore the safety profile of these drugs.

Eosinophilic oesophagitis (EoE) may lead to severe complications if not promptly recognised.To assess the diagnostic delay in patients with EoE and to explore its risk factors.EoE patients followed-up at eight clinics were included via retrospective chart review. Diagnostic delay was estimated as the time lapse occurring between the appearance of the first likely symptoms indicative of EoE and the final diagnosis. Patient-dependent and physician-dependent diagnostic delays were assessed. Multivariable regression models were computed.261 patients with EoE (mean age 34±14 years; M:F ratio=3:1) were included. The median overall diagnostic delay was 36 months (IQR 12-88), while patient- and physician-dependent diagnostic delays were 18 months (IQR 5-49) and 6 months (IQR 1-24). Patient-dependent delay was greater compared to physician-dependent delay (95% CI 5.1-19.3, p0.001). A previous misdiagnosis was formulated in 109 cases (41.8%; gastro-oesophageal reflux disease in 67 patients, 25.7%). The variables significantly associated with greater overall diagnostic delay were being a non-smoker,1 episode of food impaction, previous endoscopy with no biopsies, regurgitation, and ≥2 assessing physicians. Being single was significantly associated with lower overall and patient-dependent diagnostic delay.EoE is burdened by substantial diagnostic delay, depending on both patient-related and physician-related factors.

Long-standing inflammation leads to esophageal remodeling with stricture formation in patients with eosinophilic esophagitis (EoE). The ability of proton pump inhibitors (PPI) to reverse endoscopic features of fibrosis is still unknown.To investigate the effect of a short course of PPI treatment in reducing endoscopic findings indicative of esophageal fibrosis in EoE patients.Cross-sectional analysis of the EoE CONNECT registry. Patients who received PPI to induce EoE remission were evaluated. Endoscopic features were graded using the EoE Endoscopic Reference Score (EREFS), with rings and strictures indicating fibrosis. Results were compared to those from patients treated with swallowed topic corticosteroids (STC).Clinico-histological remission was achieved in 83/166 adult patients treated with PPI (50%) and in 65/79 (82%) treated with STC; among responders, 60 (36%) and 57 (72%) patients respectively achieved deep histological remission (5 eosinophils/hpf). At baseline, mean±SD EREFS was lower in patients treated with PPI compared to those who received STC (p 0.001). Short term treatment significantly reduced EREFS scores in patients treated either with PPI or STC as well as rings and strictures. Among patients treated with PPI, deep histological remission (5 eosinophils/hpf) provided further reduction in total EREFS score.Effective PPI therapy for EoE significantly reduced endoscopic esophageal fibrosis in the short term.

Eosinophilic esophagitis (EoE) incidence and prevalence have sharply increased in the last decade; so, the management of these patients is changing rapidly. Standard regimens as elimination diet, proton pump inhibitors and topical swallowed steroids are not able to achieve remission in all patients. Moreover, loss of efficacy and safety concerns for long-term medical treatments are rising questions. As for other chronic immune-mediated diseases, biologics have been evaluated for the treatment of EoE. Several targets in the Th2-mediated inflammatory cascade with eosinophilic mucosal infiltration, have been tested with alternating results. This review provides a comprehensive discussion of the available studies evaluating biologics in EoE and the possible future options most desirable for these patients.

BackgroundDirect comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce.AimTo compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages.MethodsCross-sectional analysis of the EoE CONNECT registry.ResultsThe adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood‐onset cohort (patients diagnosed at ConclusionsChildhood‐onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAM, The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe, The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The establishment and design of the EoE CONNECT registry was developed with a grant from the United European Gastroenterology through the National Societies Link Award program. The maintenance of the database is financed by EUREOS (European Society of Eosinophilic Oesophagitis). Funding agencies had no role in the study design, in the writing of this manuscript, or the decision to submit for publication

SUMMARY Eosinophilic esophagitis is a chronic immune-mediated esophageal disorder. For its timely diagnosis, clinicians must recognize common symptoms, and understand differences in symptoms across patient groups. The aim of this study is to systematically review the epidemiology and natural history of eosinophilic esophagitis. The MEDLINE, Embase, and Cochrane databases were searched from 1974 to February 2017 for studies describing the epidemiology and natural history of eosinophilic esophagitis. Congress abstracts from 2014 to 2016 were also searched. Search results were screened against predetermined inclusion/exclusion criteria by two independent reviewers, and data extraction was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 1376 articles identified, 47 met the inclusion criteria: 20 on epidemiology and 27 on natural history. Incidence and prevalence of eosinophilic esophagitis varied widely across North America and Europe, and increased over time. Incidence increased 131-fold in the Netherlands (1996–2010), 20-fold in Denmark (1997–2006), and 5.1-fold in Calgary, Canada (2004–2008). The most commonly reported symptoms were emesis and abdominal pain in children, and dysphagia and food impaction in adults. Age at diagnosis was 5.9–12.0 years in children, and approximately 30 years in adults. Time between symptom onset and diagnosis was 1.2–3.5 years in children and 3.0–8.0 years in adults. Diagnostic delay was associated with an increased risk of endoscopic features of fibrostenosis. Symptoms of eosinophilic esophagitis differed significantly by age and race. In conclusion, there is an increasing incidence and prevalence of eosinophilic esophagitis. The considerable delay between symptom onset and diagnosis suggests that clinicians do not readily recognize the disease, which may have important clinical ramifications.

Diagnostic delay; Endoscopy; Eosinophilic esophagitis Retraso en el diagnóstico; Endoscopia; Esofagitis eosinofílica Retard diagnòstic; Endoscòpia; Esofagitis eosinofílica Background: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. Objective: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. Methods: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. Results: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). Conclusion: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.

Gastro-esophageal reflux disease (GERD) occurs in about 25% of the general population. The complexity of the disease and the multiplicity of its clinical manifestations impair the availability of a singular diagnostic test. The majority of GERD patients do not have any endoscopically visible lesions, the so-called non-erosive reflux disease (NERD). This latter population consists of several subgroups characterized by: 1. excess of acid; 2. normal acid, but hypersensitivity to acid or weakly acidic reflux; 3. normal acid, but lack of any relationship between symptoms and reflux episodes. At present, 24-h impedance-pH monitoring represents the best diagnostic tool to detect abnormal reflux and to correlate symptoms to reflux episodes. Moreover, the recent adoption of novel impedance metrics, such as mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index, seem to be able to improve the diagnostic yield of 24-h impedance-pH monitoring, making this test the most accurate in diagnosis of GERD.

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.

Abnormal acid exposure time (AET) is associated with good outcomes of symptoms from antireflux therapy. Low esophageal mean nocturnal baseline impedance (MNBI) is an additional marker of reflux disease. We aimed to evaluate the value of MNBI when analysis of AET produces borderline or inconclusive results.We studied a retrospective cohort of 371 patients (mean age, 54.5 ± 0.7 y; 60.0% female) who had persistent reflux symptoms after treatment and underwent ambulatory pH-impedance monitoring off antisecretory therapy at 1 tertiary center in Europe or 1 in the United States. Total AET was determined from pH impedance studies (pathologic,6%; physiologic,4%; borderline or inconclusive, 4%-6%). Baseline impedance values were calculated at the 5-cm impedance channel at 3 nocturnal 10-minute periods and averaged to yield MNBI (abnormal,2292 ohms). The primary outcome was response to antireflux therapy, defined as global symptom improvement of 50% or greater on patients' answers on standardized visual analog scales.Among the 371 patients, 107 (28.8%) had pathologic AET and 234 (63.1%) had abnormal MNBI. Low MNBI was concordant in 99.1% of patients with pathologic AET, in 91.2% with borderline AET, and in 33.7% with physiologic AET. During 38.7 ± 0.8 months of follow-up evaluation, 43.0% of patients had improved symptoms with medical therapy and 76.2% had improved symptoms with surgical antireflux therapy (P.0001). When MNBI was low, response to medical therapy did not differ significantly between patients with borderline AET and patients with pathologic AET (P = .44), but did differ significantly when each group was compared with patients with physiologic AET, regardless of whether MNBI was normal or low (P.0001 for each comparison).When low, MNBI identifies patients with pathologic and borderline AET who respond to antireflux therapy. MNBI analysis complements AET in defining esophageal reflux burden. MNBI correlates with response of symptoms to antireflux therapy.

Patients with acid-related disorders (ARDs) of the upper digestive tract remain highly prevalent and need to be continuously investigated to improve their management.This review provides a summary of the most recent advancements in the treatment of ARDs with particular focus on the new drugs available to overcome the unmet needs of traditional therapies.Proton pump inhibitors remain the best therapy in treating ARDs, but a consistent proportion of these patients continues to present mucosal lesions or to experience symptoms despite treatment. These cases pertain mainly to the most severe forms of erosive esophagitis or to non-erosive reflux disease. Also, the increasing rate of patients with H. pylori infection not responding to eradication therapy represents a difficult clinical condition. The recent advent of a new class of antisecretory drugs, such as the potassium competitive acid blockers and, among them the most studied vonoprazan, which are characterized by a better pharmacological profile than PPIs (rapid onset of action, longer lasting acid suppression, control of nocturnal acidity), has the potential to overcome the above-mentioned unmet needs. More research should be done to assess their efficacy in Western populations and their safety in patients treated in the long term.

Klinefelter syndrome (KS) is a sex aneuploidy abnormality comprised by one additional X chromosome. It occurs in 1:500–1000 male births. As with women, an increased susceptibility to autoimmune diseases is present. We report three cases of coexisting EoE and KS for a prevalence of 2% in our EoE clinic. Possible changes in gene expression in KS are reviewed, some of which may be related to activation of genes located on the X chromosome. We postulate that these X-activated genes in patients with KS yield a greater likelihood of developing EoE because of their genetic predisposition to autoimmune diseases.

Simple Summary In the last decades, there has been a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the world. Although several important risk factors have been identified, strong evidence-based preventive strategies are still lacking, and the prognosis of patients diagnosed with esophageal cancer remains poor, with an average survival rate of 5 years for only 20%. This review is an attempt to summarize the epidemiology and risk factors of EC and to highlight the unresolved aspects of current prevention strategies in order to plan more fruitful future initiatives aimed at ameliorating the disappointing prognosis of this kind of digestive tumor. Abstract In the last 30 years, we have witnessed a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the word. However, despite advancements in diagnostic technologies, the early detection of this cancer is rare, and its prognosis remains poor, with only about 20% of these patients surviving for 5 years. The two major forms are the esophageal squamous cell carcinoma (ESCC), which is particularly frequent in the so-called Asian belt, and the esophageal adenocarcinoma (EAC), which prevails in Western populations. This review provides a summary of the epidemiological features and risk factors associated with these tumors. Moreover, a major focus is posed on reporting and highlighting the various preventing strategies proposed by the most important international scientific societies, particularly in high-risk populations, with the final aim of detecting these lesions as early as possible and therefore favoring their definite cure. Indeed, we have conducted analysis with attention to the current primary, secondary and tertiary prevention guidelines in both ESCC and EAC, attempting to emphasize unresolved research and clinical problems related to these topics in order to improve our diagnostic strategies and management.

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.

Background and Aims: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms. Methods: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD. Results: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett’s esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p

In the absence of secondary causes, eosinophilic esophagitis (EoE) is a chronic, local, progressive, T-helper type 2 immune-mediated disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. In the last 20 years, the incidence and prevalence of EoE have risen sharply, and the chances of encountering affected patients in clinics and endoscopy rooms have increased. Nevertheless, it is estimated that the mean diagnostic delay of EoE is 4–6 years in both children and adults. Unfortunately, the longer the disease stays unrecognized, the likelier it is for the patient to have persistent or increased esophageal eosinophilic inflammation, to complain of non-resolving symptoms, and to develop fibrotic complications. Early detection depends on the recognition of initial clinical manifestations that vary from childhood to adulthood and even among patients of the same age. The disease phenotype also influences therapeutic approaches that include drugs, dietary interventions, and esophageal dilation. We have herein reviewed epidemiologic, clinical, endoscopic, and histologic features and therapeutic options of EoE focusing on differences and similarities between children and adults that may certainly serve in daily clinical practice.

Background Postreflux swallow-induced peristaltic wave (PSPW) on pH-impedance monitoring and contraction vigor on high-resolution manometry (HRM) both assess esophageal peristaltic response. We aimed to evaluate relationships between PSPW and esophageal peristalsis on HRM in the context of reflux disease in this multicenter cohort study. Methods pH-impedance and HRM studies performed on patients with persisting reflux symptoms were reviewed from 6 centers (5 in Europe and 1 in US). Total, upright and supine acid exposure time (AET) were evaluated from pH-impedance studies; PSPW index (PSPWI) and mean nocturnal baseline impedance (MNBI) were calculated using standard methodology. Esophageal body contraction vigor was analyzed using distal contractile integral (DCI), and DCI ratio > 1 between single swallows and multiple rapid swallows (MRS) defined presence of contraction reserve. Student's t test, ANOVA, and linear regression were utilized to investigate relationships between PSPW, contraction vigor, and contraction reserve. Key results Of 296 patients (52.8 ± 0.8 yr, 63% F), median PSPWI was 0.475. Only 24.0% had intact DCI; the remainder had varying degrees of hypomotility. As hypomotility increased, PSPWI and MNBI decreased significantly, while total AET and reflux episodes had an inverse response (P ≤ .002 for each). MRS data were available in 167 (56.4%), 72.5% had contraction reserve. MRS cohorts with normal PSPWI had significantly lower reflux burden compared to low PSPWI, regardless of presence or absence of contraction reserve (P ≤ .001). Conclusions and inferences PSPWI correlates with esophageal hypomotility and reflux burden, and complements clinical reflux evaluation. Intact PSPW is more relevant to esophageal reflux clearance than contraction reserve.

Eosinophilic esophagitis (EoE) is a unique form of non-immunoglobulin E-mediated food allergy, restricted to the esophagus, characterized by esophageal eosinophil-predominant inflammation and dysfunction. The diagnosis requires an esophago-gastroduodenoscopy with esophageal biopsies demonstrating active eosinophilic inflammation with 15 or more eosinophils/high-power field, following the exclusion of alternative causes of eosinophilia. Food allergens trigger the disease, withdairy/milk, wheat/gluten, egg, soy/legumes, and seafood the most common. Therapeutic strategies comprise dietary restrictions, proton pump inhibitors, topical corticosteroids, biologic agents, and esophageal dilation when strictures are present. However, avoidance of trigger foods remains the only option targeting the cause, and not the effect, of the disease. Because EoE relapses when treatment is withdrawn, dietary therapy offers a long-term, drug-free alternative to patients who wish to remain off drugs and still be in remission. There are currently multiple dietary management strategies to choose from, each having its specific efficacy, advantages, and disadvantages that both clinicians and patients should acknowledge. In addition, dietary regimens should be tailored around each individual patient to increase the chance of tolerability and long-term adherence. In general, liquid elemental diets devoid of antigens and elimination diets restricting causative foods are valuable options. Designing diets on the basis of food allergy skin tests results is not reliable and should be avoided. This review summarizes the most recent knowledge regarding the clinical use of dietary measures in EoE. We discussed endpoints, rationale, advantages and disadvantages, and tailoring of diets, as well as currently available dietary regimens for EoE.

The treatment for coeliac disease (CD) has a considerable psychological impact on patients, which may vary depending on subjects and clinical characteristics. The aim of this study was to describe the quality of life (QoL) in CD patients during follow-up, evaluating which factors can influence it. Patients with CD who consecutively visited the outpatient clinic of CD Unit of the University Hospital of Padua from January to September 2019 were enrolled. Demographics and clinical information were collected, and all patients were asked to answer the CD-QoL and Biagi&rsquo, s validated questionnaires. Student&rsquo, s t-test and chi-square test were used to compare the continuous and categorical variables, respectively. One hundred patients were enrolled (86 females, mean age at test &plusmn, SD: 39.73 &plusmn, 13.51, mean age at diagnosis &plusmn, SD: 33.09 &plusmn, 12.92), with 61% of them having been diagnosed with CD within the previous 5 years. At the time of diagnosis, 43 CD patients reported classical CD presentation, 32 non-classical features, 16 only anaemia and 9 were asymptomatic. The mean CD-QoL value was overall high (80.54 &plusmn, 11.91). We found that the &ldquo, health concerns&rdquo, subscale score was significantly lower in subjects aged more than 35 years compared to younger subjects (p = 0.03). We also observed that the CD-QoL score in gluten-free diet (GFD)-adherent patients tended to be higher compared to subjects who were non-compliant, with a significantly higher percentage of patients with low score for the &ldquo, dysphoria&rdquo, subscale (p = 0.05). This study showed an overall good QoL in subjects on a GFD. However, subjects older and non-compliant to GFD appear to experience more health concerns and suffer from dysphoria, respectively.

INTRODUCTION: There are no real-life studies comparing the efficacy and safety of the different antitumor necrosis factor (TNF)-α drugs available in patients with ulcerative colitis (UC) and Crohn's disease (CD). To verify the effectiveness and tolerability of different anti–TNF-α agents (infliximab [IFX] originator, biosimilar CTP13, and adalimumab [ADA]) in patients with moderate-to-severe CD and UC. METHODS: Retrospectively, patients with moderate-to-severe inflammatory bowel disease who completed induction with either ADA, IFX originator, or biosimilar from 2015 to 2017 were included. Patients were evaluated after induction at 30 and 52 weeks. We performed an intention-to-treat analysis to evaluate clinical response and remission, steroid-free clinical remission, and endoscopy response according to different time points. At every time point, the need for dose escalation and occurrence of adverse events have been reported. RESULTS: Eighty-nine patients with UC (31 ADA, 30 IFX originator, and 28 IFX biosimilar) and 90 patients with CD (30 for each drug groups) were enrolled. After induction at week 30 and 52, clinical response was obtained by the following: 84.3%, 86.5%, and 82% of UC and 93.3%, 88.9%, and 80% of CD. Clinical steroid-free remission rates were significantly higher in the CD group compared with the UC group at every time point (P < 0.05). At week 52, 31.1% of ADA, 16.7% of IFX originator, and 36.2% of biosimilar patients needed treatment optimization. At week 52, 13 patients had suspended therapy because of severe adverse events, including 3 cases of malignant disease. DISCUSSION: Anti–TNF-α treatment was more effective in patients with CD compared to patients with UC, independently of the drug used.

Background/Aims The role of esophageal high-resolution manometry (HRM) within Lyon consensus phenotypes, especially patients with inconclusive gastroesophageal reflux disease (GERD) evidence, has not been fully investigated. In this multicenter, observational study we aim to compare HRM parameters in patients with GERD stratified according to the Lyon consensus. Methods Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH (MII-pH) studies performed off proton pump inhibitor therapy in patients with esophageal GERD symptoms were reviewed. Lyon consensus criteria identified pathological GERD, reflux hypersensitivity, functional heartburn, and inconclusive GERD. Patients, with inconclusive GERD were further subdivided into 2 groups based on total reflux numbers (≤ 80 or > 80 reflux episodes) during the MII-pH recording time. Results A total of 264 patients formed the study cohort. Pathological GERD and inconclusive GERD patients were associated with higher numbers of reflux episodes, lower mean nocturnal baseline impedance (MNBI) values, and a higher proportion of patients with pathologic MNBI compared to functional heartburn (P < 0.05 for each comparison). On multivariate analysis, pathological GERD and inconclusive GERD patients, both with ≤ 80 or > 80 reflux episodes, were significantly associated with pathologic esophagogastric junction contractile integral values and with presence of hiatus hernia (type 2/3 esophagogastric junction). Patients with inconclusive GERD and > 80 reflux episodes were significantly associated with fragmented peristalsis and ineffective esophageal motility whilst inconclusive GERD with ≤ 80 reflux episodes were significantly associated with fragmented peristalsis. Conclusion Esophageal motor parameters on HRM are similar between pathologic and inconclusive GERD according to the Lyon consensus.

Background: Faecal microbiota transplantation (FMT) is a reasonable therapeutic option for the treatment of Clostridioides difficile infection (CDI) recurrent and refractory (RCDI) to therapy, but little evidence on the long-term impact of this therapy is currently available in the literature. The aim of this study was to evaluate the efficacy and safety of FMT in recurrent and refractory CDI and the modifications of the recipient’s gut microbiota in the medium–long term. Methods: This prospective study collects the clinical and laboratory data of RCDI patients treated with FMT by colonoscopy from February 2016 to October 2019. Stool samples for metagenomic analysis were collected pre-FMT at 1 week and at 6 and 12–24 months post-FMT. Results: In the study period, 20 FMT procedures were performed on 19 patients. Overall, FMT was effective in 85% of treated patients. No serious adverse event was recorded. In the medium- to long-term follow up, a newly diagnosed case of collagenous colitis was observed. Post-FMT, significant changes in microbiota were observed, characterised by the transition from a low- to a greater-diversity profile. Therefore, FMT restores eubiosis and maintains it over time. Conclusion: FMT is a safe and effective treatment option in RCDI patients. This procedure induces profound microbiota changes that explain its high clinical efficacy.

Eosinophilic gastrointestinal diseases (EGIDs) are chronic gastrointestinal conditions requiring corticosteroid and immunosuppressive therapy for disease control. Patients with EGIDs usually report impaired quality of life. We aimed to report the clinical and psychological impact of COVID-19 infection in EGID patients. In this prospective web-based study we invited all consecutive EGID patients attending the University Hospital of Salerno (Campania) and Padua (Veneto) to fill an ad hoc COVID-19 survey. Moreover, a telemedicine service for direct consultation was organized. Data regarding the occurrence and perception of COVID-19 infection as well as clinical information were recorded. The study population included 102 EGID patients (mean age 36.6 years, 34 females), of whom 89 had eosinophilic esophagitis, nine had gastroenteritis, and four had colitis. No patient was diagnosed with COVID-19 or had recurrence of his/her primary disease. All of them were adherent to therapy and preventive measures adoption. Most patients were worried because of COVID-19 and social preventing measures but did not consider themselves at major risk or susceptible to COVID-19 or other infections due to their chronic condition or therapy. Female gender and low education level were associated to a higher psychological perception of COVID-19 compared to lockdown status or other demographic and clinical factors (p &lt, 0.05). Overall, COVID-19 had a limited clinical impact on patients with EGIDs. The degree of education and sex, but not the fact of living in a lockdown area, influenced the perception of SARS-CoV-2 infection.

BACKGROUND Mean nocturnal baseline impedance (MNBI) augments the diagnostic yield of multichannel intraluminal impedance-pH (MII-pH) monitoring. While acid exposure time (AET) correlates with MNBI, it remains unclear whether esophageal motility affects MNBI values. The present study was aimed at evaluating the respective roles of esophageal motor function and AET on MNBI. METHODS High-resolution manometry (HRM) studies and ambulatory 24-hour MII-pH monitoring tracings were retrospectively analyzed from consecutive endoscopy-negative GERD patients with typical symptoms responsive to previous acid-suppressive therapy from three tertiary care centers. Univariate and multivariate analyses were performed to determine predictors of pathologic MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES). KEY RESULTS Patients with pathological AET displayed lower MNBI values at 3 cm and 5 cm (P