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Background: Supragastric belching (SGB) and aerophagia are behavioral disorders characterized by air induced esophageal distension. SGB is known to be associated with Gastro Esophageal Reflux Disease (GERD). Low Mean Nocturnal Baseline Impedance (MNBI) values support GERD diagnosis. We aimed to assess if chronic esophageal distension by air affects the esophageal mucosa integrity by assessing changes in MNBI., Methods: In a single-center database study, we searched retrospectively for patients with a diagnosis of pathological SGB (n = 146) or aerophagia (n = 34) based on impedance-pH reflux monitoring. During the examined period, patients with a conclusive negative diagnosis of SGB and no evidence of aerophagia were used as a control cohort (n = 191). MNBI at 3, 5, and 17 cm over Lower Esophageal Sphincter (LES) was evaluated. GERD was diagnosed if acid exposure time (AET) >6%. All impedance studies of included patients were prospectively reevaluated., Results: GERD was diagnosed in 31.7% patients with SGB, a rate not different in comparison to patients without SGB (30.8%, p = 0.906). MNBI at 3 and 5 cm above the LES was significantly decreased among patients with SGB. SGB was not correlated with MNBI at 3 cm over the LES, (p: 0.086 OR: 1.000 95% CI: 0.999-1.001) when using multivariate analysis. Moreover no difference was spotted as far as MNBI at 3, 5, and 17 cm over the LES is concerned among patients with or without aerophagia., Conclusion: Even if patients with SGB do show lower MNBI values, esophageal distention due to excessive air movement does not directly lead to impairment of esophageal mucosa integrity., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Reflux hypersensitivity (RH) is characterized by normal esophageal exposure to acid and positive correlation of symptoms to reflux episodes. Positivity of Symptomatic Index (SI) and/or Symptom Association Probability (SAP) is used diagnostically, though experts support that concordance of both is needed. We evaluated differences among patients with RH and concordance of SI/SAP or not., Methods: Patients with typical reflux symptoms without previous GERD diagnosis, submitted simultaneously to Ph-Impedance off PPI and high resolution manometry were included. Self-response to PPI was evaluated. Patients showing SI and/or SAP positivity were considered having RH and further classified to definite RH if both SI/SAP were positive or indefinite if only one positive., Key Results: Totally 2659 patients (M/F: 35.6%/64.7%, mean age: 45 ± 14) were included. Final diagnosis was; FH: 21.8%, RH: 29.3% (definite: 14.3%/indefinite: 15%), GERD: 36% and inconclusive GERD: 12.9%. Patients with definite RH showed increased total reflux time, total number of reflux episodes and length of hiatus hernia, and also numerically but not statistically significant increased rates of PPI responsiveness versus indefinite RH and decreased mean nocturnal baseline impedance. Moreover, they showed significantly increased rate of PPI response versus patients with functional heartburn (FH)., Conclusion & Inferences: Some PPI responsiveness is frequent among patients with RH as also with FH, and cannot discriminate those entities clinically when diagnosing RH using SI and/or SAP positive criterion. Patients with RH and SI/SAP concordance differ from patients without. Implementation of a strict RH definition (both SI and SAP positive) can better distinguish RH from FH and should be used in the future., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Aim: Low mean nocturnal baseline impedance (MNBI) values support gastroesophageal reflux disease (GERD) diagnosis. Recent data denote that age and obesity may affect MNBI. We aimed to evaluate diagnostic MNBI cutoffs as also the effect of aging and body mass index (BMI) on MNBI., Methods: In total 311 patients (M/F: 139/172, mean age: 47 ± 13) referred for typical GERD symptoms that have undertaken both high-resolution manometry (HRM) and pH-Impedance studies off PPI were evaluated. MNBI at 3, 5, and 17 cm over lower esophageal sphincter (LES) were evaluated. GERD was diagnosed if acid exposure time (AET) >6%., Results: Mean BMI was 26.6 ± 5.9 kg/cm 2 . GERD was diagnosed in 39.2% and 13.5% had inconclusive GERD. MNBI was correlated to patients' age, BMI, AET, and the length of LES-CD separation and at 3 cm also to the total number of reflux and LES hypotension. In the multivariate analysis MNBI at 3 and 5 cm was independently correlated only to age, BMI, and AET. Patients with definite GERD showed lower MNBI at 3 cm compared with inconclusive GERD though both showed lower values when compared with GERD absence. At 3 cm MNBI ability for diagnosing GERD was good (0.815, p < 0.001 95% CI: 0.766-0.863) with an optimal cutoff point of 1281 Ohm., Conclusion: According to our study findings age and BMI affect independently lower esophageal MNBI values in patients evaluated for GERD. MNBI significantly aids toward GERD diagnosis though in a real-life setting MNBI values much lower than the one previously proposed should be used., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Supragastric belching (SGB) is a phenomenon where air is rapidly sucked from the pharynx into the esophagus and immediately expelled through abdominal straining. It is considered a behavior disorder and is increasingly recognized not only in patients with excessive belching, but also in those with reflux-like symptoms. Increased prevalence of esophageal hypomotility and increased acid exposure were previously reported in small cohorts of SGB patients. We aimed to clarify the impact of SGB on motility, reflux, and acid exposure in a large cohort of SGB patients., Methods: In a single-center database study, we searched for patients with pathological SGB. MII-pH and Manometry tracings were manually re-evaluated in all patients. Demographic, clinical, motility, reflux, and SGB-related data were gathered., Key Results: Three hundred and forty-eight patients were included. Heartburn, belching, and regurgitation were the most common symptoms. Ineffective esophageal motility (IEM) was found in 27% of patients. SGB related to 47% of all reflux and to 53.6% of acid reflux events, and accounted for 27.3% of acid exposure time (AET). In those with severe SGB, 62% of acid reflux events and 46% of AET were SGB-related., Conclusions & Inferences: Supragastric belching is common, associated with higher incidence of IEM and is responsible for almost a third of esophageal acid burden. The impact of SGB is proportional to its severity. Diagnosis of SGB should be sought in patients with excessive belching and in patients with refractory reflux symptoms. Recognizing SGB and treating patients with behavioral therapy may alleviate acid exposure and improve quality of life., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Paraesophageal hernias (PEH) can be associated with obstructive symptoms, but high-resolution manometry (HRM) characteristics have not been described in detail., Methods: HRM studies of confirmed PEH patients (n = 60, 66.3 ± 1.5 years, 76.7% F), axial hernias (n = 125, 56.1 ± 1.1 years, 58.4% F), and healthy controls (n = 20, 27.9 ± 0.7 years, 45% F) were analyzed. Axial hernias (type 1) were compared to PEH subtyped as isolated PEH (type 2), PEH with axial hernia (type 3), PEH with herniated abdominal organs (type 4), and unknown. Distal contractile integral (DCI), esophageal length, lower esophageal sphincter pressures (LESP), EGJ contractile integral (EGJ-CI), and integrated relaxation pressure (IRP) were extracted. Intra-luminal pressures were measured proximal (intrabolus pressure, IBP) and distal (intragastric pressure, IGP) to EGJ. Univariate and multivariate analyses were performed to characterize esophageal and EGJ motor physiology in PEH., Key Results: PEH patients had LESP and EGJ-CI similar to controls; axial hernia patients had lower LESP. While IRP was within normal limits, PEH had elevated IBP and IGP, and shorter esophageal length compared to axial hernia and normal controls (P ≤ .0001 across groups). Short esophageal length was consistent across PEH subtypes (P = .06). On multivariate regression analysis, IBP remained an independent predictor of PEH (P < .0001). Within PEH subtypes, gastric pressure was higher when axial HH was also present, in contrast to isolated PEH (P = .03); other metrics did not differ., Conclusions & Inferences: Luminal pressure increase both upstream and downstream of the EGJ on HRM likely represents obstructive phenomena in PEH, identification of which may support suspicion of PEH., (© 2020 John Wiley & Sons Ltd.)

Background: Pathophysiology of rumination syndrome (RS) is not well understood. Treatment with diaphragmatic breathing improves rumination syndrome. The aim of the study was to characterize vagal tone in patients with rumination syndrome during and after meals and during diaphragmatic breathing., Methods: We prospectively recruited 10 healthy volunteers (HV) and 10 patients with RS. Subjects underwent measurement of vagal tone using heart rate variability. Vagal tone was measured during baseline, test meal and intervention (diaphragmatic (DiaB), slow deep (SlowDB), and normal breathing). Vagal tone was assessed using mean values of root mean square of successive differences (RMSSD), and area under curves (AUC) were calculated for each period. We compared baseline RMSSD, the AUC and meal-induced discomfort scores between HV and RS. Furthermore, we assessed the effect of respiratory exercises on symptom scores, and number of rumination episodes., Key Results: There was no significant difference in baseline vagal tone between HV and RS. During the postprandial period, there was a trend to higher vagal tone in RS, but not significantly (P > .2 for all). RS had the higher total symptom scores than HV (P < .011). In RS, only DiaB decreased the number of rumination episodes during the intervention period (P = .028), while both DiaB and SlowDB increased vagal tone (P < .05 for both). The symptom scores with the 3 breathing exercises showed very similar trends., Conclusions and Inferences: Patients with RS do not have decreased vagal tone related to meals. DiaB reduced number of rumination events by a mechanism not related to changes in vagal tone., (© 2020 John Wiley & Sons Ltd.)

Background: Discontinuation of long-term proton pump inhibitors (PPIs) on patients with reflux symptoms can be challenging, as symptoms often exacerbate after stopping. The mechanism remains unknown. Our aim was to evaluate the impact of stopping long-term PPIs on patients with heartburn, and its association with esophageal acid exposure., Methods: Patients with heartburn on long-term PPIs underwent symptom questionnaire, high-resolution manometry, and 24h ambulatory impedance-pH studies, following a 7-day PPIs discontinuation. We investigated the association between exacerbation of symptoms and findings on ambulatory reflux studies., Key Results: We studied 37 patients. After stopping PPIs, 27 patients (73%) had exacerbation of heartburn. Esophageal acid exposure time% (AET) in patients with exacerbation of heartburn was not significantly higher than in patients without (3.5% [1.3-9.7] vs 2.5% [1.3-8.7], NS). Fourteen of 27 patients with exacerbation had physiological AET (<4%) as compared with 6 of 10 patients with physiological AET (NS). All questioned symptoms (heartburn, regurgitation, epigastric discomfort/pain, bloating/belch) worsened after stopping PPIs (NS)., Conclusions & Inferences: Exacerbation of heartburn after discontinuation of PPIs does not appear to be due to increased esophageal acid exposure., (© 2019 John Wiley & Sons Ltd.)

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.