Value of endoscopic grading of gastroesophageal flap valve in gastroesophageal reflux disease.

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.

A new formula proposal for placing pH-impedance catheters in pediatric patients.

INTRODUCTION: Esophageal pH-impedance monitoring is a tool for diagnosing gastroesophageal reflux in children. The position of the pH catheter is essential for a reliable reading and the current formulas for calculating catheter insertion length are not completely accurate. The aim of the present study was to develop a new formula for adequate insertion of the pH catheter. MATERIAL AND METHODS: A cross-sectional study was conducted on children that underwent pH-impedance monitoring and later radiographic control, to calculate the correct catheter insertion length. The documented variables were age, sex, weight, height, naris to tragus distance, tragus to sternal notch distance, sternal notch to xiphoid process distance, and initial insertion length determined by the Strobel and height interval formulas. A multivariate regression analysis was carried out to predict the final insertion length. Regression ANOVA and Pearson's adjusted R-squared tests were performed. RESULTS: Forty-five pH-impedance studies were carried out, 53% of which were in males. The age and weight variables were not normally distributed. In the initial regression model, the variables that did not significantly correlate with the final insertion length were: sex (P 0.124), length determined by the Strobel or height interval formulas (P 0.078), naris to tragus distance (P 0.905), and tragus to sternal notch distance (P 0.404). The final equation: 5.6 + (height in cm * 0.12) + (sternal notch to xiphoid process distance * 0.57) produced an R2 of 0.93 (P 0.000). CONCLUSIONS: This formula can be considered a valid option for placement of the pH-impedance monitoring catheter in pediatrics.

Saliva Production and Esophageal Motility Influence Esophageal Acid Clearance Related to Post-reflux Swallow-Induced Peristaltic Wave.

BACKGROUND: The post-reflux swallow-induced peristaltic wave (PSPW) brings salivary bicarbonate to neutralize residual distal esophageal mucosal acidification. AIMS: To determine if reduced saliva production and esophageal body hypomotility would compromise PSPW-induced pH recovery in the distal esophagus. METHODS: In this multicenter retrospective cross-sectional study, patients with confirmed Sjogren's syndrome and scleroderma/mixed connective tissue disease (MCTD) who underwent high resolution manometry (HRM) and ambulatory pH-impedance monitoring off antisecretory therapy were retrospectively identified. Patients without these disorders undergoing HRM and pH-impedance monitoring for GERD symptoms were identified from the same time-period. Acid exposure time, numbers of reflux episodes and PSPW, pH recovery with PSPW, and HRM metrics were extracted. Univariate comparisons and multivariable analysis were performed to determine predictors of pH recovery with PSPW. RESULTS: Among Sjogren's syndrome (n = 34), scleroderma/MCTD (n = 14), and comparison patients with reflux symptoms (n = 96), the scleroderma/MCTD group had significantly higher AET, higher prevalence of hypomotility, lower detected reflux episodes, and very low numbers of PSPW (p ≤ 0.004 compared to other groups). There was no difference in pH-impedance metrics between Sjogren's syndrome, and comparison patients (p ≥ 0.481). Proportions with complete pH recovery with PSPW was lower in Sjogren's patients compared to comparison reflux patients (p = 0.009), predominantly in subsets with hypomotility (p < 0.001). On multivariable analysis, diagnosis of Sjogren's syndrome, scleroderma/MCTD or neither (p = 0.014) and esophageal hypomotility (p = 0.024) independently predicted lack of complete pH recovery with PSPW, while higher total reflux episodes trended (p = 0.051). CONCLUSIONS: Saliva production and motor function are both important in PSPW related pH recovery.

Higher obesity class is associated with more severe esophageal symptoms and reflux burden but not altered motor function or contractile reserve.

BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance. METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes. KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures. CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.

Esophageal Mucosal Admittance: A New Technique to Diagnose Gastroesophageal Reflux Disease - Is It Feasible?

Purpose: Esophageal mucosal admittance (MA) is a promising diagnostic method for gastroesophageal reflux disease (GERD). We conducted a study to describe the esophageal MA in patients with reflux symptoms and determine its diagnostic accuracy. Patients and Methods: We recruited 92 patients with ambulatory pH-impedance monitoring, upper gastrointestinal endoscopy, and MA measured by the tissue conductance meter. MA was measured during endoscopy at 5cm (distal esophagus) and 15cm above the Z line (middle esophagus), repeated at least five times at each position, and median MA was obtained. Afterwards, two biopsies were taken 5cm above the Z line for histopathological evaluation using the Esohisto criteria. Patients were classified as GERD or non-GERD according to the 2018 Lyon consensus. Results: The mean age was 43.2 years, and 42 patients were males. The most common symptoms were regurgitation (75.0%), belching (65.2%), and heartburn (46.7%). Twenty-three (32.3%) were diagnosed with GERD using the Lyon consensus, and 24 (26.1%) had esophagitis on histopathology. The median MA at the distal and middle esophagus was moderately correlated. The median MA at both positions was higher in the GERD group but only statistically significant in the middle esophagus. MA was not associated with pH-impedance parameters and esophagitis on histopathology. The diagnostic model developed using the logistic regression did not have good accuracy. Conclusion: MA was not different between GERD and non-GERD patients.

Esophagogastric junction contractile integral (EGJ-CI) complements reflux disease severity and provides insight into the pathophysiology of reflux disease.

BACKGROUND: Esophagogastric junction contractile integral (EGJ-CI) has not come into routine use due to methodological discrepancies and its unclear clinical utility. We aimed to determine which method of calculating EGJ-CI was best at discriminating between common reflux disease states. METHODS: High-resolution manometry (HRM) and pH-Impedance measurements were acquired for 100 patients; 25 Barrett's esophagus (>3 cm/acid exposure time (AET) > 6), 25 endoscopy-negative reflux disease (ENRD; AET >6), 25 borderline reflux (AET 4-6), 25 functional heartburn (FH; AET <4), constituting the developmental cohort. EGJ-CI was calculated at 20 mmHg, 2 mmHg, and 0 mmHg isobaric contour. Empirical associations, univariable, multivariable and ROC analyses were performed between EGJ-CI and manometric/pH-impedance metrics. A validation cohort (n = 25) was used to test the new EGJ-CI cutoff. KEY RESULTS: Significant correlations with AET were observed when EGJ-CI was calculated with an isobaric threshold of 20 mmHg (p < 0.001). Significant differences in EGJ-CI were observed between patients with FH and Barrett's esophagus (p = 0.004) and with ENRD (p = 0.01); however, LES basal pressure was unable to differentiate between these disease states (p = 0.09, p = 0.25, respectively). ROC analysis on the developmental cohort found that EGJ-CI 21.2 mmHg.cm demonstrated sensitivity 72% and specificity 72% between patients with reflux (Barrett's esophagus/ENRD) and FH. In the validation cohort, 92.8% with a low EGJ-CI had good/moderate improvement in symptoms following therapy compared to 54.5% with raised EGJ-CI (p = 0.026). CONCLUSIONS AND INFERENCES: This study re-affirms EGJ-CI as a reliable discriminator between reflux disease (Barrett's esophagus/ENRD) and FH. In borderline reflux patients, patients with a lower EGJ-CI score (<21.2 mmHg) appear to respond better to anti-reflux therapies compared to those with a higher value.

Episode-level reflux characteristics: How experienced reviewers differentiate true reflux from artifact on pH-impedance studies.

BACKGROUND: Accurate reflux episode identification is crucial for pH-impedance interpretation. Individual reflux episode characteristics associated with inter-reviewer concordance are incompletely understood. METHODS: Ambulatory pH-impedance studies from 19 GERD patients (median age 52 years, 78.9% F) were analyzed by 5 reviewers. Metadata from pH-impedance studies were exported to a dedicated software tool designed to compare episode-by-episode identification between reviewers within a ±7.5 s window. Patient position, acidic vs. nonacidic episodes, acid clearance time (ACT), bolus clearance time (BCT), and proximal extent of reflux episodes were compared between episodes identified by all reviewers against those identified by automated analysis, and one to four reviewers, respectively. RESULTS: Automated analysis identified 1644 episodes (median 78 episodes per patient, IQR 64-108), of which 84.9% were identified by ≥3 reviewers and 57.1% by all reviewers; 339 unique episodes were added by at least 1 reviewer. Characteristics defining 5 reviewer concordance included acid reflux episodes (88.9%), upright episodes (88.4%), high proximal extent (median 17 cm, IQR 15-17 cm), and longer acid clearance times (67.0 s, IQR 29.0-146.0 s) (P < 0.001 compared to 1-4 reviewer concordance for each). In contrast, 1 reviewer-identified episodes were 69.8% acidic, 76.9% upright, and limited to the distal esophagus. Using 5-reviewer concordance, designation of GERD evidence changed from automated analysis in 16%-19% of patients. CONCLUSIONS: Acidic episodes with high proximal extent in the upright position and longer acid clearance times on pH-impedance studies have the highest concordance for identification by expert reviewers. Reflux episode identification may be influenced by reviewer opinion despite availability of established criteria.

Phenotyping patients with borderline elevated esophageal acid exposure.

Acid exposure time (AET) <4% on ambulatory reflux monitoring definitively rules out pathologic gastroesophageal acid reflux, while AET >6% indicates pathologic reflux per the Lyon Consensus, leaving AET of 4-6% as borderline. We aimed to elucidate the borderline AET population and identify metrics that could help differentiate this group. A total of 50 subjects in each group, AET <4, 4-6, and >6% on pH-impedance monitoring between 2015 and 2019, were retrospectively reviewed. In addition to demographic and clinical information, the extracted data included mean nocturnal baseline impedance (MNBI) on reflux study and high-resolution manometry (HRM) parameters and diagnosis. After excluding patients with prior foregut surgery, major esophageal motility disorder, or unreliable impedance testing, a total of 89 subjects were included in the analysis (25 with normal AET < 4%, 38 with borderline 4-6%, 26 with abnormal >6%). MNBI in borderline AET patients was significantly lower compared to normal AET (1607.7 vs. 2524.0 ohms, P < 0.01), and higher than abnormal AET (951.5 ohms, P < 0.01). Borderline subjects had a greater frequency of ineffective esophageal motility (IEM) diagnosis per Chicago classification v3.0 (42.1 vs. 8.0%, P = 0.01), but did not demonstrate any differences compared to abnormal subjects (34.6%, P = 0.56). Patients with borderline AET had an average MNBI that was in between normal AET and abnormal AET. Borderline AET patients also commonly demonstrate IEM on HRM, similar to those with abnormal AET. Our findings can be potentially useful in assigning higher clinical significance for patients found to have borderline AET with concomitant low MNBI and IEM on manometry.

Comparison of esophageal motility and reflux characteristics of patients with endoscopic-negative heartburn based on the Lyon Consensus / 西安交通大学学报(医学版)

【Objective】 To explore the characteristics of esophageal motility and reflux of endoscopic-negative heartburn patients based on the Lyon Consensus Diagnostic Criteria and discuss the differential diagnosis value of the mean nocturnal baseline impedance （MNBI） and the postreflux swallow-induced peristaltic wave （PSPW） index for reflux hypersensitivity （RH） and functional heartburn （FH） patients. 【Methods】 We enrolled 132 patients with heartburn as the main symptom who visited the Gastroenterology Department of our hospital from January 2017 to June 2021， including 24 in the non-erosive reflux disease （NERD） group， 24 in the RH group， and 84 in the FH group. All the patients completed gastroscopy， esophageal high-resolution manometry and 24h-pH impedance monitoring. We analyzed and compared the related indexes of esophageal motility and reflux. The receiver operating characteristic （ROC） curve was used to analyze the esophageal proximal MNBI， distal MNBI， and PSPW indexes for the differential diagnosis of RH and FH. 【Results】 The lower esophageal sphincter （LES） average resting pressure， LES residual pressure and intact relaxation pressure （IRP） in NERD were lower than those in RH and FH （P0.05）. When the proximal MNBI， distal MNBI， and PSPW indexes were used alone respectively to diagnose RH， the area under the ROC curve was 0.480， 0.810， 0.682， respectively， with the sensitivities being 87.5%， 100% and 91.7%， and the specificities being 26.2%， 66.7% and 51.2%， respectively. 【Conclusion】 NERD patients have obvious abnormal esophageal dynamics， mainly manifested as LES relaxation， which further aggravates the pathological acid reflux， while patients with RH and FH are mainly exposed to physiological acid or non-acid reflux. In patients with endoscopic negative heartburn， distal MNBI value can improve the clinical diagnosis rate of RH and help distinguish RH from FH.

Diagnosis and Management of Refractory Gastroesophageal Reflux Disease.

In up to half of patients with symptoms suspected to stem from gastroesophageal reflux disease (GERD), these symptoms persist despite treatment with daily proton pump inhibitor (PPI) therapy. The symptoms may be characterized as typical (eg, heartburn or regurgitation) or atypical (eg, chest pain or cough). These refractory symptoms, which are frequently encountered in clinical practice, may stem from GERD as well as non-GERD etiologies. Among those patients with objective GERD proven on esophagogastroduodenoscopy (EGD) and/ or ambulatory reflux testing, approximately one-fifth may manifest suboptimal symptom response to PPI therapy. After introducing the initial evaluation of patients with suspected GERD symptoms, this article discusses approaches to the esophageal diagnostic workup of patients with refractory symptoms in the setting of proven GERD, focusing on EGD, high-resolution manometry (HRM), and pH-impedance monitoring during treatment with PPI therapy. EGD evaluates for esophagitis, peptic stricture, and hiatal hernia, as well as eosinophilic esophagitis. HRM rules out confounding esophageal motor disorders, identifies behavioral disorders, characterizes the antireflux barrier, and assesses esophageal contractile reserve to help tailor potential antireflux interventions. pH-impedance monitoring during treatment with PPI therapy can help distinguish between PPI-refractory GERD-as evidenced by pathologic acid exposure despite PPI therapy and/or excess burden of reflux events regardless of acidity-and PPI-controlled GERD. This article also discusses potential approaches for patients with symptoms stemming from refractory GERD, encompassing lifestyle, pharmacologic, endoscopic, and surgical management options.

Value of pH Impedance Monitoring While on Twice-Daily Proton Pump Inhibitor Therapy to Identify Need for Escalation of Reflux Management.

BACKGROUND AND AIMS: Acid exposure time (AET) and reflux episode thresholds from the Lyon Consensus may not apply for pH impedance studies performed while on proton pump inhibitor (PPI) therapy. We aimed to determine metrics from "on PPI" pH impedance studies predicting need for escalation of therapy. METHODS: De-identified pH impedance studies performed while on twice-daily PPI (Diversatek, Boulder, CO) in healthy volunteers (n = 66, median age 37.5 years, 43.9% female), and patients with proven gastroesophageal reflux disease (GERD) (European heartburn-predominant cohort: n = 43, median age 57.0 years, 55.8% female; North American regurgitation-predominant cohort: n = 42, median age 41.6 years, 42.9% female) were analyzed. Median values and interquartile ranges for pH impedance metrics in healthy volunteers were compared with proven GERD patients with and without 50% symptom improvement on validated measures. Receiver operating characteristic (ROC) analyses identified optimal thresholds predicting symptom response. RESULTS: Both conventional and novel reflux metrics were similar between PPI responders and nonresponders (P ≥ .1 for each) despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (AET >4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, respectively, 57.1% and 82.4% of whom reported nonresponse; and 85% with these metrics improved with invasive GERD management. On ROC analysis, AET threshold of 0.5% modestly predicted nonresponse (sensitivity, 0.62; specificity, 0.51; P = .22), and 40 reflux episodes had better performance characteristics (sensitivity, 0.80; specificity, 0.51; P = .002); 79% with these metrics improved with invasive GERD management. CONCLUSION: Combinations of abnormal "on PPI" pH impedance metrics are associated with PPI nonresponse in proven GERD patients, and can be targeted for treatment escalation, including surgery, particularly in regurgitation-predominant GERD.

Actualización en la interpretación de la medición del pH e impedanciometría / Updated interpretation of Impedance-pH monitoring

Resumen La enfermedad por reflujo gastroesofágico (ERGE) se define como el tránsito anormal del contenido gástrico hacia el esófago, que se da por una alteración de la barrera antirreflujo, causando síntomas o complicaciones. Para su correcto diagnóstico y abordaje terapéutico, se requiere de la integración de hallazgos clínicos, endoscópicos y monitorización del pH esofágico en 24 horas con o sin impedanciometría, la cual debe ser realizada con especificaciones técnicas, y su interpretación debe basarse en la mejor evidencia clínica disponible, con el objetivo de tener diagnósticos precisos que permitan tomar las mejores decisiones con los pacientes. Recientemente, en el Consenso de Lyon se han incorporado nuevas directrices para el diagnóstico de ERGE por monitorización de pH esofágico, las cuales se revisan en este artículo.

Abstract Gastroesophageal reflux disease (GERD) is defined as the abnormal transit of gastric contents into the esophagus. It is caused by an alteration of the anti-reflux barrier, causing multiple symptoms or complications. In order to achieve accurate diagnosis and proper therapeutic approach, integration of clinical findings, endoscopic findings and 24-hour esophageal pH monitoring, with or without impedancometry, is required. These tests must be performed following technical specifications and their interpretation must be based on the best clinical evidence available to obtain accurate diagnoses that allow making the best decisions to the benefit of patients. Recently, the Lyon Consensus incorporated new guidelines for the diagnosis of GERD by esophageal pH monitoring, which are reviewed in this paper.

ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro-esophageal reflux disease.

Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term "refractory GERD" has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term "refractory GERD symptoms" only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.

Plasma dosage of ghrelin, IGF-1, GLP- 1 and leptin related to gastric emptying and esophageal pH-impedance in children with obesity.

PURPOSE: The main aim of the study was to assess the relationship between leptin, ghrelin, insulin-like growth factor 1 (IGF-1), and glucagon-like peptide 1 (GLP-1) blood levels and gastric motility in children with obesity compared to healthy children. Secondary aims were to assess the possible association between these hormones and obesity, reflux impedance parameters, reflux symptoms, other GI disorders, and quality-of-life scores within the same groups. METHODS: Children with obesity plus GERD symptoms and 2 control groups of children with obesity without GERD and healthy lean children aged 4-17 years underwent an auxological evaluation, an assessment of gastro-intestinal symptoms and quality of life, hormonal dosages, and an evaluation of gastric emptying time (GET) through 13C-octanoic acid breath test. RESULTS: No significant association was found between hormones and gastric motility. Leptin and ghrelin levels were significantly associated with obesity parameters. No significant differences were found between GET and hormones of the patients with obesity, either with or without GERD. CONCLUSION: Although we found an association between auxological parameters and both leptin and ghrelin levels, this association did not imply an effect on the upper GI motility. Therefore, our hypothesis that alterations of these hormones in children with obesity could affect gastric emptying, triggering GERD, was not supported by our data.

Overlap of functional heartburn and reflux hypersensitivity with proven gastroesophageal reflux disease.

BACKGROUND: When esophageal acid exposure time (AET) is physiologic, ROME IV stratifies functional esophageal disorders into functional heartburn (FH, with negative reflux-symptom association) and reflux hypersensitivity (RH, with positive reflux-symptom association), and hypothesizes that FH/RH could overlap with proven gastroesophageal reflux disease (GERD). We compared conventional FH/RH diagnosed off antisecretory therapy with overlap FH/RH coexisting with proven GERD. METHODS: Adult patients with heartburn underwent pH-impedance testing on therapy (proven GERD) and off therapy (unproven GERD) and completed validated questionnaires defining symptoms (Reflux Diagnostic Questionnaire, RDQ), affective state (Hospital Anxiety and Depression Scale, HADS; Visceral Sensitivity Index, VSI), and functional diagnoses (irritable bowel syndrome, IBS; functional dyspepsia, FD on ROME diagnostic questionnaire). AET (pathologic: >6%, physiologic <4%) and mean nocturnal baseline impedance (MNBI) were calculated. Clinical, psychological, and functional profiles were compared between FH and RH and to a comparison cohort of non-erosive reflux disease (NERD, AET > 6%). KEY RESULTS: Study patients included 19 with RH (10 with overlap RH), 60 with FH (31 with overlap FH), and 26 patients with NERD. Clinical, psychological, and functional profiles of conventional FH/RH were similar to overlap FH/RH. Compared with NERD, combined FH and RH cohorts had higher anxiety scores, and lower proportions with IBS. Compared with FH with low MNBI, FH defined using both normal AET and normal MNBI had higher depression scores (p = 0.008), and trended toward higher anxiety scores (p = 0.059). CONCLUSIONS AND INFERENCES: Conventional and overlap FH and RH have similar clinical, psychological and functional profiles, thereby proving ROME IV hypotheses.

Artificial intelligence automates and augments baseline impedance measurements from pH-impedance studies in gastroesophageal reflux disease.

BACKGROUND: Artificial intelligence (AI) has potential to streamline interpretation of pH-impedance studies. In this exploratory observational cohort study, we determined feasibility of automated AI extraction of baseline impedance (AIBI) and evaluated clinical value of novel AI metrics. METHODS: pH-impedance data from a convenience sample of symptomatic patients studied off (n = 117, 53.1 ± 1.2 years, 66% F) and on (n = 93, 53.8 ± 1.3 years, 74% F) anti-secretory therapy and from asymptomatic volunteers (n = 115, 29.3 ± 0.8 years, 47% F) were uploaded into dedicated prototypical AI software designed to automatically extract AIBI. Acid exposure time (AET) and manually extracted mean nocturnal baseline impedance (MNBI) were compared to corresponding total, upright, and recumbent AIBI and upright:recumbent AIBI ratio. AI metrics were compared to AET and MNBI in predicting ≥ 50% symptom improvement in GERD patients. RESULTS: Recumbent, but not upright AIBI, correlated with MNBI. Upright:recumbent AIBI ratio was higher when AET > 6% (median 1.18, IQR 1.0-1.5), compared to < 4% (0.95, IQR 0.84-1.1), 4-6% (0.89, IQR 0.72-0.98), and controls (0.93, IQR 0.80-1.09, p ≤ 0.04). While MNBI, total AIBI, and the AIBI ratio off PPI were significantly different between those with and without symptom improvement (p < 0.05 for each comparison), only AIBI ratio segregated management responders from other cohorts. On ROC analysis, off therapy AIBI ratio outperformed AET in predicting GERD symptom improvement when AET was > 6% (AUC 0.766 vs. 0.606) and 4-6% (AUC 0.563 vs. 0.516) and outperformed MNBI overall (AUC 0.661 vs. 0.313). CONCLUSIONS: BI calculation can be automated using AI. Novel AI metrics show potential in predicting GERD treatment outcome.

Comparative study on the parameters between reflux asthma and typical gastroesophageal reflux disease / 中华消化杂志

Objective:To analyze the difference and clinical significance of reflux related parameters between patients with reflux asthma (RA) and typical gastroesophageal reflux disease (TGERD).Methods:From June 2017 to June 2020, at PLA Rocket Force Characteristic Medical Center, the clinical data of 120 patients with gastroesophageal reflux disease (GERD) who underwent gastroscopy, high-resolution esophageal manometry (HREM) and 24 h pH-impedance monitoring contemporaneously were retrospectively analyzed. The GERD patients were divided into RA group and TGERD group according to the symptom correlated indexes, 60 cases in each group. The reflux related indexes of two groups were compared, which included reflux esophagitis (RE) score, esophageal hiatal hernia, Hill grade score of gastroesophageal flap valve, upper esophageal sphincter (UES) pressure, DeMeester score, and reflux episodes. Mann-Whitney U test and chi-square test were used for statistical analysis. Results:There were no significant differences in RE score and Hill grade score between TGERD group and RA group (0.0, 0.0 to 1.0 vs. 0.0, 0.0 to 1.8; 3.0, 2.0 to 3.0 vs. 3.0, 2.0 to 3.0) (both P>0.05). The detection rate of UES pressure less than 34 mmHg (1 mmHg=0.133 kPa) of RA group was higher than that of TGERD group (41.7%, 25/60 vs. 23.3%, 14/60), and the difference was statistically significant ( χ2=4.596, P=0.032). The UES pressure of RA group was lower than that of TGERD group (51.7 mmHg, 23.6 mmHg to 70.1 mmHg vs. 62.0 mmHg, 37.4 mmHg to 77.4 mmHg), and the difference was statistically significant ( Z=-2.105, P=0.035). There were no significant differences in other parameters of HREM between TGERD group and RA group (all P>0.05). The detection rates of DeMeester score more than 14.7, acid exposure time more than 4.5% and total reflux episodes more than 73 episodes of RA group were all higher than those of TGERD group (41.7%, 25/60 vs. 23.3%, 14/60; 40.0%, 24/60 vs. 21.7%, 13/60; 38.3%, 23/60 vs. 20.0%, 12/60, respectively), and the differences were all statistically significant ( χ2=5.546, 4.728 and 4.881, all P<0.05). The total reflux episodes and weak acid gas reflux episodes of RA group were both higher than those of TGERD group (60 episodes, 43 episodes to 98 episodes vs. 52 episodes, 34 episodes to 69 episodes; 12 episodes, 6 episodes to 21 episodes vs. 9 episodes, 3 episodes to 14 episodes), and the differences were statistically significant ( Z=-2.323 and -2.053, both P<0.05). There were no significant differences in other parameters of 24 h pH-impedance monitoring between TGERD group and RA group (all P>0.05). Conclusion:Low UES pressure, abnormal esophageal acid exposure and increased reflux episodes, especially weak acid gas reflux episodes, may be more likely to induce RA.

[Esophageal pH-impedance monitoring of reflux patterns in non-erosive reflux disease, reflux hypersensitivity and functional heartburn].

OBJECTIVE: To analyze the differences in reflux patterns in 24-hour esophageal pH-impedance monitoring in patients with non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) and explore the possible mechanism of symptoms in patients with heartburn and negative endoscopic findings. METHODS: Seventy-nine patients with heartburn as the main symptoms but negative endoscopic findings, including 35 with NERD, 16 with RH and 28 with FH, were enrolled in this study.All the patients underwent 24-h esophageal pH-impedance monitoring and esophagogastroscopy, and the results were compared among the 3 groups. RESULTS: Acid reflux episode was significantly increased and weakly alkaline reflux episode was significantly decreased in NERD group in comparison with RH group and FH group (P < 0.05).The patients in NERD group showed significantly increased total reflux episode, mixed reflux episode, proximal acid reflux episode, proximal weak acid reflux episode, total proximal reflux episode, percentage of proximal acid reflux, percentage of proximal weak acid reflux, and percentage of total proximal reflux as compared with the other two groups (all P < 0.05).Bolus clear time was significantly prolonged in NERD group compared with that in the other two groups (P < 0.05).Analysis of the reflux acidity showed that the percentages of different reflux episodes differed significantly among the 3 groups (P < 0.05);acid reflux was the main reflux in NERD, while weak acid reflux was the main reflux in RH and FH groups, which had also significantly increased weakly alkaline reflux episodes compared with NERD group. CONCLUSIONS: Patients with NERD, RH and FH had different reflux patterns.Acid reflux is predominant in the NERD, while weakly alkaline reflux is significantly increased RH and FH.In patients with normal esophageal acid exposure but without symptoms or without recorded symptoms during esophageal pH-impedance monitoring, analysis of the total reflux episode, mixed reflux episode, proximal acid reflux episode and percentage can help in the differential diagnosis between RH and FH.

[Clinical characteristics and esophageal function tests of refractory gastroesophageal reflux disease].

Objective: To analyze the clinical characteristics and pathogenesis of refractory gastroesophageal reflux disease(RGERD). Methods: The patients with acid regurgitation, heartburn and extraesophageal symptoms were enrolled in the study from November 2015 to September 2017 at Peking University Third Hospital. All the subjects filled the informed consent.Questionnaire, SCL-90, SAS and SDS scales were recorded. A 24 hour pH-impedance monitoring and esophageal high resonance manometry were carried out. According to the response to proton pump inhibitor(PPI), the patients were divided into RGERD and non-RGERD(NRGERD)groups. The clinical characteristics were compared between these two groups. Logistic regression was used to analyze the risk factors of RGERD. Results: One hundred and nineteen patients were finally enrolled in the study including 61 RGERD (51.3%) and 58 NRGERD patients (48.7%).The body mass index (BMI) and rates of, typical GER symptoms including acid regurgitation in RGERD patients were significantly lower than those in NRGERD patients (P<0.05).While the atypical GER symptoms such as poststernal discomfort or chest pain were more common in RGERD group (P<0.05).RGERD patients presented less acid reflux events and lower proximal segment reflux ratio than NRGERD patients. No obvious differences were found in the manometry metrics between these two groups. The scores of somatization, depression and hostility in RGERD patients by SCL-90 scales were significantly higher than those in NRGERD patients (P<0.05), and depression score was an independent risk factor for RGERD [OR=3.915 (95%CI 1.464-10.466), P =0.007]. Conclusions: RGERD patients present more atypical symptoms and pathological non-acid reflux.Depression is an independent risk factor for RGERD.

Esophageal contractile segment impedance from high-resolution impedance manometry correlates with mean nocturnal baseline impedance and acid exposure time from 24-hour pH-impedance monitoring.

Esophageal baseline impedance (BI) acquired during esophageal contraction (contractile segment impedance [CSI]) is proposed to improve BI accuracy in gastroesophageal reflux disease (GERD). We evaluated associations between CSI and conventional and novel GERD metrics. We analyzed high-resolution impedance manometry (HRIM) and ambulatory pH-impedance studies from 51 patients (58.6 ± 1.5 years; 26% F) with GERD symptoms studied off antisecretory therapy. Patients with achalasia or absent contractility were excluded. CSI (averaged across 10 swallows) and BI-HRIM (from the resting landmark phase) were acquired from the distal impedance sensors (distal sensor and 5 cm above the lower esophageal sphincter). Acid exposure time (AET) and mean nocturnal baseline impedance (MNBI) were calculated. Associations between CSI, BI-HRIM, MNBI, and AET were evaluated using correlation (Pearson) and receiver operating characteristic (ROC) analysis. Presenting symptoms included heartburn (67%), regurgitation (12%), cough (12%), and chest pain (10%). CSI-distal and CSI-5 each correlated with BI-HRIM, AET, and distal MNBI. Associations with AET were numerically stronger for CSI-distal (r = -0.46) and BI-HRIM-distal (r = -0.44) than CSI-5 (r = -0.33), BI-HRIM-5 (r = -0.28), or distal MNBI (r < -0.36). When compared to AET <4%, patients with AET >6% had significantly lower CSI-distal and BI-HRIM-distal values but not CSI-5, BI-HRIM-5, or MNBI. ROC areas under the curve for AET >6% were numerically higher for CSI-distal (0.81) than BI-HRIM-distal (0.77), distal MNBI (0.68-0.75), CSI-5 (0.68), or BI-HRIM-5 (0.68). CSI from HRIM studies inversely correlates with pathologic AET and has potential to augment the evaluation of GERD.