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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., (© 2020 John Wiley & Sons Ltd.)

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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: Head-to-head comparison studies evaluating the effectiveness and tolerability of anti-tumor necrosis factor (anti-TNF) drugs in inflammatory bowel disease patients are lacking., Aim: To compare the effectiveness and tolerability of anti-TNF-α drugs used in clinical practice in a cohort of patients with moderate-to-severe ulcerative colitis (UC)., Methods: Retrospectively, 122 UC patients treated with infliximab (IFX) originator and biosimilar, adalimumab (ADA), and golimumab (GOL) were included. We performed an ITT analysis to evaluate clinical response and remission, steroid-free clinical remission, and endoscopy response according to the different time points of the follow-up. Baseline and post induction predictor factors of these outcomes were evaluated using multivariate logistic regression models. Moreover, a propensity score-based weighting analysis was performed. Data were analyzed using R and STATA11 software., Results: The overall clinical response was 77% after induction, 81.4% at 30 weeks, and 76.9% at 52 weeks, while the steroid-free clinical remission was 39.7, 46, and 54.6%, respectively. After induction, a higher rate of treatment failure was observed in the GOL group. At the end of follow-up, lower rates of steroid-free clinical remission and clinical response were obtained by GOL. At week 52, endoscopic response was achieved by 46.5% of the population., Conclusions: Among the different anti-TNF treatments, moderate-to-severe UC seems to respond better to IFX and ADA, whereas GOL seems to be less effective, despite a similar good safety profile., (© 2020 S. Karger AG, Basel.)

Background/aims: Impaired esophageal motility and disrupted esophagogastric junction (EGJ) on high-resolution manometry (HRM) have been associated with increased reflux severity in gastroesophageal reflux disease (GERD) patients. However, there are limited data evaluating HRM parameters in proton pump inhibitors (PPI) non-responders., Methods: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH studies performed of PPI therapy in patients with typical GERD symptoms were reviewed from 3 international centers. Frequency of GERD symptoms was assessed on and off PPI therapy in both non-responders (< 50% symptom improvement on PPI therapy) and responders. Rome IV definitions identified non-erosive reflux disease, reflux hypersensitivity, and functional heartburn. Univariate and multivariate analyses were performed to determine predictors of non-response., Results: Of 204 patients, 105 were PPI non-responders and 99 were responders. Non-responders showed higher EGJ contractile integral values, and a lower frequency of type II and III EGJ morphology ( P ≤ 0.03 for each comparison). Esophageal body diagnoses on HRM (fragmented peristalsis, ineffective esophageal motility, or absent peristalsis) did not predict non-response. On multivariate analysis, non-pathological acid exposure time (OR, 2.5; 95% CI, 1.2-5.0; P < 0.001), normal mean nocturnal baseline impedance values (OR, 2.7-2.4; 95% CI, 1.0-6.1; P < 0.05), normal EGJ contractile integral values (OR, 3; 95% CI, 1.3-7.4; P = 0.012), and presence of type I EGJ morphology (OR, 1.9; 95% CI, 1.0-3.4; P = 0.044) were associated with an unfavorable response to PPIs., Conclusions: Intact EGJ metrics on HRM complement normal reflux burden in predicting non-response to PPI therapy. HRM has value in the evaluation of PPI non-responders.

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's validated questionnaires. Student'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 ± SD: 39.73 ± 13.51; mean age at diagnosis ± SD: 33.09 ± 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 ± 11.91). We found that the "health concerns" 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 "dysphoria" 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.

Gastroesophageal reflux disease (GERD) is a complex disorder with heterogeneous symptoms and a multifaceted pathogenetic basis, which prevent a simple diagnostic algorithm or any categorical classification. Clinical history, questionnaires and response to proton pump inhibitor (PPI) therapy are insufficient tools to make a conclusive diagnosis of GERD and further investigations are frequently required. The Lyon Consensus goes beyond the previous classifications and defines endoscopic and functional parameters able to establish the presence of GERD. Evidences for reflux include high-grade erosive esophagitis, Barrett's esophagus, and peptic strictures at endoscopy as well as esophageal acid exposure time > 6% on pH-metry or combined pH-impedance monitoring. Even if a normal endoscopy does not exclude GERD, its combination with distal acid exposure time < 4% on off-PPI pH-impedance monitoring provides sufficient evidence refuting this diagnosis. Reflux-symptom association on pH-monitoring provides supportive evidence for reflux-triggered symptoms and may predict a better treatment outcome, when present. Also recommendations to perform pH-impedance "on" or "off" PPI are well depicted. When endoscopy and pH-metry or combined pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (eg, microscopic esophagitis), high-resolution manometry (ie, ineffective esophagogastric barrier and esophageal body hypomotility), and novel impedance metrics, such as mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index, can contribute to better identify patients with GERD. Definition of individual patient phenotype, based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the esophagogastric junction, and clinical presentation, will lead to manage GERD patients with a tailored approach chosen among different types of therapy.

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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

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 < 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.

Beyond the small intestine, coeliac disease (CeD) may affect other gastrointestinal tracts, including the stomach. However, various studies have reported conflicting results regarding the association between CeD and gastric manifestations. The aim of this study was to analyze the existing literature on gastric involvement in CeD. A literature search was conducted in bibliographic databases of Embase, PubMed, Scopus, and Web of Science. Studies reporting the association between CeD and gastric disorders were examined in detail and are fully described in the review. Both in children and adults, a strong correlation between lymphocytic gastritis and CeD was found at CeD diagnosis, and lymphocytic gastritis seemed to improve on a gluten-free diet. Most of the literature described a lower risk of gastritis related to Helicobacter pylori infection in CeD subjects compared to controls. However, due to the discordance among studies in terms of study design and population, a clear association could not be determined. Finally, the relationship between CeD and reflux or dyspepsia has yet to be defined, as well as the association between CeD and autoimmune gastritis. CeD appears to be a multiform entity associated with different gastric disorders with a different degree of relationship. Thus, gastric biopsies should be routinely taken during upper endoscopy in CeD patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Marabotto et al.)

Background and Aims: Inflammatory bowel diseases (IBDs) are treated with anti-TNF agents. Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Previous evidence suggests cleavage of infliximab (IFX) by Matrix Metalloproteinase 3 (MMP3) as a mechanism leading to loss of response. Our study aimed to evaluate if MMP3 serum levels could be considered an early marker of anti-TNF nonresponse and to analyze the correlation with other biochemical markers of treatment failure such as IFX trough levels and anti-IFX antibodies, inflammatory markers, and albumin levels., Methods: Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks. Clinical and biochemical data (Harvey-Bradshaw index [HBI], Mayo score, body mass index [BMI], C-reactive protein [CRP], fecal calprotectin and albumin levels), MMP3 serum levels, and drug monitoring were assessed at baseline, postinduction, and 52 weeks., Results: The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001). The MMP3 levels tended to be higher in patients without antidrug antibodies than in patients with antidrug antibodies at postinduction and 52 weeks., Conclusions: The MMP3 serum determination may represent an early marker of response to infliximab., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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 < .01) compared to patients with non-pathological AET. Similarly, significantly lower MNBI values were also noted at both sites with type 3 EGJ compared to type 1 EGJ (P ≤ .02 for each comparison), and with absent contractility compared to normal peristalsis (P ≤ .02 for each comparison). On multivariate analysis, the presence of type 2 or 3 EGJ and absent contractility were associated with a significantly higher probability of pathological MNBI values at 3 cm and 5 cm above the LES., Conclusions and Inferences: Disruption of the EGJ and absent contractility on HRM are both associated with lower MNBI values. HRM findings complement reflux testing using MII-pH monitoring., (© 2019 John Wiley & Sons Ltd.)

Background: Association between proportions of hypomotile swallows on esophageal high-resolution manometry (HRM) and esophageal reflux burden remains incompletely understood. We investigated relationships between hypomotility, acid exposure time (AET), and mean nocturnal baseline impedance (MNBI) on ambulatory reflux monitoring., Methods: Clinical data, HRM, and ambulatory pH-impedance studies (performed off acid suppression) from patients with persisting reflux symptoms were reviewed from five international centers. AET (abnormal > 6%) and MNBI (abnormal < 2292 ohms) were extracted from pH-impedance studies. Distal contractile integral (DCI) designated esophageal peristalsis into normal (DCI > 450 mmHg.cm.s), fragmented (DCI > 450 mmHg.cm.s with breaks > 5 cm), weak (DCI 100-450 mmHg.cm.s), and failed (DCI < 100 mm mmHg.cm.s) sequences. Univariate and multivariate analyses were performed to identify motor associations of abnormal reflux burden., Key Results: Of 351 patients (52.1 ± 0.8 years, 67%F), 29.3% had AET > 6% and 61.8% had MNBI < 2292 ohms. On univariate analysis, both fragmented peristalsis and IEM associated with abnormal AET (P ≤ .01) and MNBI (P ≤ .03); reflux burden was more profound with >70% fragmented as well as ineffective sequences compared to ≤70% for each (P < .05 for each comparison). When weak and failed sequences within IEM were separately analyzed, ≥50% failed sequences predicted abnormal AET (P ≤ .009), and ≥50% weak sequences did not (P = .14). On multivariate regression, ≥50% failed sequences predicted abnormal AET (P = .02), and >70% ineffective sequences trended strongly (P = .069); >70% ineffective sequences predicted abnormal MNBI (P = .046), and >70% fragmented sequences trended strongly (P = .076)., Conclusions and Inferences: Breaks in esophageal peristaltic integrity seen with fragmented and failed sequences are more relevant to abnormal esophageal acid burden than weak sequences., (© 2019 John Wiley & Sons Ltd.)

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., Competing Interests: Edoardo Savarino received lecture and consultancy honoraria from Takeda, Janssen, MSD, Abbvie, Sofar, Malesci, Reckitt Benckiser, and Medtronic. Matteo Ghisa, Carla Marinelli, and Vincenzo Savarino had no conflicts of interests to report in this work., (© 2019 Ghisa et al.)

Introduction : Gastroesophageal reflux disease (GERD) is one of the most prevalent conditions in Western Countries, normally presenting with heartburn and regurgitation. Extra-esophageal (EE) GERD manifestations, such as asthma, laryngitis, chronic cough and dental erosion, represent the most challenging aspects from diagnostic and therapeutic points of view because of their multifactorial pathogenesis and low response to proton pump inhibitors (PPIs). In fact, in the case of EE, other causes must by preventively excluded, but instrumental methods, such as upper gastrointestinal endoscopy and laryngoscopy, have low specificity and sensitivity as diagnostic tools. In the absence of alarm signs and symptoms, empirical therapy with a double-dose of PPIs is recommended as a first diagnostic approach. Subsequently, impedance-pH monitoring could help to define whether the symptoms are GERD-related. Areas covered : This article reviews the current literature regarding established and proposed EE-GERD, reporting on all available options for its correct diagnosis and therapeutic management. Expert opinion : MII-pH could help to identify a hidden GERD that causes EE. Unfortunately, standard MII-pH analysis results are often unable to define this association. New parameters such as the mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index may have an improved diagnostic yield, but prospective studies using impedance-pH are needed.

Background: Esophageal hypercontractility can manifest with and without esophagogastric junction (EGJ) outflow obstruction. We investigated clinical presentations and motility patterns in patients with esophageal hypercontractile disorders., Methods: Esophageal HRM studies fulfilling Chicago Classification 3.0 criteria for jackhammer esophagus (distal contractile integral, DCI >8000 mmHg.cm.s in ≥ 20% swallows) with (n = 30) and without (n = 83) EGJ obstruction (integrated relaxation pressure, IRP > 15 mm Hg) were retrospectively reviewed from five centers (4 in Europe, 1 in US). Single swallows (SS) and multiple rapid swallows (MRS) were analyzed using HRM software tools (IRP, DCI, distal latency, DL); MRS: SS DCI ratio >1 defined contraction reserve. Comparison groups were achalasia type 3 (n = 72, positive control for abnormal inhibition and EGJ obstruction) and healthy controls (n = 18). Symptoms, HRM metrics, and MRS contraction reserve were analyzed within jackhammer subgroups and comparison groups., Key Results: The esophageal smooth muscle was excessively stimulated at baseline in jackhammer subgroups, with lack of augmentation following MRS identified more often compared with controls (P = .003) and type 3 achalasia (P = .07). Consistently abnormal inhibition was identified in type 3 achalasia (47%), and to a lower extent in jackhammer with obstruction (37%, P = .33), jackhammer esophagus (28%, P = .01), and controls (11%, P < .01 compared with type 3 achalasia). Perceptive symptoms (heartburn, chest pain) were common in jackhammer esophagus (P < .01 compared with type 3 achalasia), while transit symptoms (dysphagia) were more frequent with presence of EGJ obstruction (P ≤ .01 compared with jackhammer without obstruction)., Conclusions and Inferences: The balance of excessive excitation and abnormal inhibition defines clinical and manometric manifestations in esophageal hypercontractile disorders., (© 2019 John Wiley & Sons Ltd.)

Background: Mucosal innervation in non-erosive reflux disease (NERD; pathological esophageal acid exposure, normal macroscopic mucosa) is clearly distinct from that of healthy volunteers (HV) and from patients with esophagitis or Barrett's esophagus: The nerves in NERD are situated much closer to the luminal surface of the mucosa. Patients with functional heartburn (FH) have a similar symptom profile to patients with NERD and indistinguishable macroscopic appearances. However, they have physiological acid exposure and no reflux-symptom association. The aim of our study was to delineate the position of esophageal mucosal nerve fibers in patients with FH and compare it with that in NERD and HV., Methods: Distal esophageal biopsies from patients with FH were immunohistochemically stained for CGRP. CGRP-positive nerve fibers were identified, and their position relative to the lumen was determined. These results were compared to our previously published cohort of HV and NERD., Results: Eleven patients were included in the FH group with a mean age of 46 years (range 33-69); 7F:4M. Nine patients had visible nerve fibers. The location of the afferent nerve fibers in the distal esophageal mucosa (median of 22, range 10.4-28) was similar to the HV group (median 25.5) and significantly deeper than the superficial nerves seen in NERD (median 9.5)., Conclusions: The mucosal innervation pattern in FH is more alike that of healthy individuals than that of NERD, with afferent nerves lying deep in the mucosa, away from the luminal surface. This supports the theory that heartburn in FH has a distinct nociceptive pathophysiology., (© 2019 John Wiley & Sons Ltd.)

Background/aim: Inflammatory bowel disease (IBD) is a chronic disorder affecting patients' quality of life and increasing their disability. The aim of our study was to evaluate clinical and pharmacological factors associated with impaired quality of life and disability in a large cohort of IBD patients during IBD treatment., Methods: We consecutively and prospectively recruited all IBD patients referred to the IBD Unit of the "Azienda Ospedaliera" of Padua. Demographics and clinical information were collected, and all patients completed the IBD questionnaire (IBDQ) and the IBD-Disability Index (IBD-DI) questionnaire. A multivariate regression model and Spearman's rank correlation coefficient were applied for detecting IBD-related variables relevant to disability and quality of life., Results: We included 435 IBD patients. Multivariate regression modelling identified active disease, anaemia, presence of extraintestinal manifestations, and Crohn subtype as independent predictors for both disability and poor quality of life. We observed a strong positive correlation between IBD-DI and IBDQ ( r = 0.84, p < 0.001), while there was no association with ongoing therapy or other clinical features disease-related., Conclusions: Our study showed that disability and quality of life are both associated with active disease, anaemia, presence of extraintestinal manifestations, and Crohn phenotype while ongoing therapy seems not to be associated with disability and QoL during disease management., Competing Interests: None of the authors declared any conflicts of interest or disclosed any financial relationship relevant to this publication.

Competing Interests: None

Introduction: The utilization of high-resolution manometry (HRM) has enhanced our understanding and assessment of esophageal motor disorders. Moreover, the combination of impedance technology with HRM (HRIM) has further improved our knowledge of esophageal physiology and the clinical evaluation of dysmotility, thanks to the addition of accurate measurement of bolus transit. Areas covered. This paper provides an overview of current knowledge in the use of HRIM for the study of esophageal functional disorders by reporting mainly the results of many publications and several systematic reviews in this field. Expert opinion. HRIM has represented a relevant improvement in the assessment of esophageal motility and has required the development of new metrics, such as the esophageal impedance integral ratio, the bolus flow time, the nadir impedance pressure and the impedance bolus height, which increase the evaluation of esophageal bolus transit. An extension of impedance is represented by functional lumen imaging probe (FLIP), which determines the biophysical properties and the distensibility of the esophagus and permits to detect contractility patterns not seen on HRM alone. We eagerly wait for a new and fruitful iteration of the Chicago Classification, now in version 3.0, which can cover the ongoing clinical experience of HRIM.

Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Proton pump inhibitors (PPIs) have become the first choice medical treatment of acid-related disease and, as with any pharmacological agent, they have been reported to be associated with some adverse events mainly linked to their chronic use. The most important postulated harms are represented by serum electrolyte alterations, vitamin B12 and iron deficiency, gastric tumors, enteric infections, spontaneous bacterial peritonitis, pneumonia, ischemic heart attacks, bone fractures, chronic kidney disease, dementia, and Alzheimer disease. Specific pathophysiological mechanisms have been identified for some of them and not for other manifestations., Areas Covered: However, studies on PPIs safety have generally important limitations because of their frequent retrospective design and other methodological drawbacks, such as patients' selection and residual confounders., Expert Opinion: Obviously, in the vast majority of the cases, adverse drug reactions cannot be assessed by means of randomized clinical trials due to the high costs, ethical reasons, and difficulties in performing prospective observational studies. So far, assessment of retrospective observational investigations remains the only method to evaluate adverse events with any drug in general and, although the weaknesses of these studies are evident, the awareness of the reported associations with the medications analyzed is important for physicians in order to manage adequately their individual patients.