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La fisiopatología de la enfermedad por reflujo gastroesofágico es multifactorial. Los eventos involucrados se inician en el estómago y, en forma ascendente, afectan la unión gastroesofágica y el esófago. Las características del material refluido impactarán en la magnitud del daño mucoso y en la percepción sintomática. Existen mecanismos defensivos y factores agresores, que son determinantes de la enfermedad. La intensidad con la que se perciben los síntomas es variable en cada individuo y está determinada por una combinación de mecanismos modulados por el sistema nervioso central y periférico, y factores psicológicos como la hipervigilancia. Las alteraciones en el aclaramiento esofágico junto con el tipo de material refluido probablemente sean los mayores determinantes para el desarrollo de una enfermedad de tipo erosiva, mientras que la sensibilidad de la mucosa lo sea para la percepción sintomática. El desarrollo de la enfermedad por reflujo gastroesofágico es el producto de un desbalance entre los factores mencionados anteriormente. Entender cuál es el mecanismo fisiopatológico predominante permite ofrecer al paciente el mejor tratamiento disponible.

This study aimed to evaluate the in vivo protective effect of the angico gum biopolymer in reducing the inflammatory response and preserving the integrity of the laryngeal and esophageal mucosa.Animal study.A murine surgical model of gastroesophageal reflux disease was accomplished and subsequently treated with angico gum or omeprazole. On days 3 and 7 post surgery, samples of the larynx and esophagus, respectively, were collected to measure the level of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and mucosal permeability to fluorescein).Angico gum and omeprazole decreased laryngeal inflammation (wet weight and myeloperoxidase activity) and dramatically improved the integrity of the laryngeal mucosa. It also reduced inflammation (decreased wet weight and myeloperoxidase activity) of the esophagus and preserved the barrier function (inferred by assessing the integrity of the mucosa).This study demonstrates the protective effect of angico gum in an experimental gastroesophageal reflux disease model. Angico gum attenuates inflammation and impairment of the mucosal barrier function not only in the larynx but also in the esophagus.NA Laryngoscope, 133:162-168, 2023.

La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en un periodo de dos años. Las actualizaciones claves de la CCv4.0 consisten en un protocolo de HRM más riguroso y expansivo que incorpora las posiciones en decúbito supino y sedestación, así como pruebas provocadoras; una definición refinada de la obstrucción del flujo de salida de la unión esofagogástrica (EGJOO), criterios diagnósticos más estrictos para la motilidad esofágica inefectiva, y descripción de la métrica basal de la EGJ. Adicionalmente, la CCv4.0 se propuso definir el diagnóstico de alteración de la motilidad como conclusivo o no conclusivo con base en los síntomas asociados, los hallazgos en las pruebas provocadoras, y los resultados de los exámenes de apoyo como el esofagograma con tableta de bario y/o la prueba con sonda para imagen endoluminal funcional. Estos cambios buscan minimizar la ambigüedad presente en iteraciones previas de la Clasificación de Chicago; además proveen criterios más estandarizados y rigurosos para los patrones de alteración de la peristalsis y obstrucción de la EGJ.

The underlying causes of heartburn, characteristic symptom of gastroesophageal reflux disease (GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease (NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1 (TRPV1), transient receptor potential melastatin 8 (TRPM8), and acid-sensing ion channel 3 (ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterized TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of patients with GERD. We studied 10 patients with NERD, 10 with erosive reflux disease (ERD), 7 with functional heartburn (FH), and 8 with Barrett's esophagus (BE). Biopsies obtained from the distal esophageal mucosa were costained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of

Hiatus hernia (HH) contributes to development of gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma. This study was aimed to investigate the influence of HH on reflux patterns and distal esophageal mucosal integrity in non-erosive reflux disease (NERD).We retrospectively analyzed PPI-refractory NERD patients referred to three tertiary referral centers who underwent high-resolution manometry and off-PPI 24-h impedance-pH monitoring (with or without bile spectrophotometry). Patients with HH ≥2 cm (HH group, n = 42) or no HH (non-HH group, n = 40) with similar esophageal acid exposure time (AET 6%-12%) were included.Age, gender, BMI, esophageal motility, AET, and esophageal clearance were similar between the two groups. The HH group had higher numbers of total reflux episodes (p = 0.015) with similar proportion of acid/non-acid reflux compared with the non-HH group. Mean nocturnal baseline impedance (MNBI) in the distal esophagus was significantly lower in the HH group than the non-HH group at both 5 cm (p = 0.002) and 3 cm (p = 0.015) above the lower esophageal sphincter. Multivariable regression analysis showed that HH, less non-acid reflux and lower post-reflux swallow-induced peristaltic wave index (PSPWI) were independently associated with lower MNBI. Among 31 patients tested with bile spectrophotometry, the HH group had significantly longer bile exposure time than the non-HH group (p = 0.011), and bile reflux inversely and significantly correlated with MNBI (rho = -0.75, p lt; 0.001).Hiatus hernia, less non-acid reflux and lower PSPWI were associated with lower MNBI. HH impairs distal esophageal mucosal integrity, the mechanism of which we speculate to be through excessive bile reflux.

Refractory reflux-like symptoms have a substantial impact on patients and healthcare providers. The aim of the survey was to qualitatively assess the needs and attitudes of practicing clinicians around the management of refractory reflux symptoms and refractory gastroesophageal reflux disease (rGERD).An International Working Group for the Classification of Oesophagitis (IWGCO) steering committee invited clinicians to complete an online survey including 17 questions.Of the 113 clinicians who completed the survey, 70% were GIs, 20% were primary care physicians, and 10% were other specialties. Functional heartburn was considered the most common reason for an incomplete response to proton pump inhibitor (PPI) therapy (82%), followed by stress/anxiety (69%). More GIs identified esophageal hypersensitivity as a cause, while more non-GIs identified esophageal dysmotility and non-reflux-related esophageal conditions. As the first step, most clinicians would order investigations (70-88%). Overall, 72% would add supplemental therapy for patients with partial response, but only 58% for those with non-response. Antacid/alginate was the most common choice overall, while non-GIs were more likely to add a prokinetic than were GIs (47.8 vs. 24.1%). Approximately 40% of clinicians would switch PPIs in patients with partial response, but only 29% would do so in non-responders. Preferences for long-term therapy were highly variable. The most common initial investigation was upper endoscopy. Choice of esophageal manometry and pH monitoring was more variable, with no clear preference for whether pH monitoring should be conducted on, or off, PPI therapy.The survey identified a number of challenges for clinicians, especially non-GI physicians, treating patients with refractory reflux-like symptoms or rGERD on a daily basis.

Achalasia is a rare disorder of the oesophageal smooth muscle characterized by impaired relaxation of the lower oesophageal sphincter (LES) and absent or spastic contractions in the oesophageal body. The key pathophysiological mechanism is loss of inhibitory nerve function that probably results from an autoimmune attack targeting oesophageal myenteric nerves through cell-mediated and, possibly, antibody-mediated mechanisms. Achalasia incidence and prevalence increase with age, but the disorder can affect all ages and both sexes. Cardinal symptoms consist of dysphagia, regurgitation, chest pain and weight loss. Several years can pass between symptom onset and an achalasia diagnosis. Evaluation starts with endoscopy to rule out structural causes, followed by high-resolution manometry and/or barium radiography. Functional lumen imaging probe can provide complementary evidence. Achalasia subtypes have management and prognostic implications. Although symptom questionnaires are not useful for diagnosis, the Eckardt score is a simple symptom scoring scale that helps to quantify symptom response to therapy. Oral pharmacotherapy is not particularly effective. Botulinum toxin injection into the LES can temporize symptoms and function as a bridge to definitive therapy. Pneumatic dilation, per-oral endoscopic myotomy and laparoscopic Heller myotomy can provide durable symptom benefit. End-stage achalasia with a dilated, non-functioning oesophagus may require oesophagectomy or enteral feeding into the stomach. Long-term complications can, rarely, include oesophageal cancer, but surveillance recommendations have not been established.

OBJECTIVE Although pathological acid reflux in patients with reflux symptoms is uncommon, it affects one-third of patients with epigastric symptoms in China. The aim of this study was to evaluate and compare the relevance of esophageal and epigastric symptoms in diagnosing gastroesophageal reflux disease (GERD) in China. METHODS Consecutive outpatients with predominantly esophageal symptoms (heartburn, regurgitation, chest pain, dysphagia) or predominantly epigastric symptoms (epigastric pain, epigastric burning, early satiety, postprandial fullness) were enrolled. Patients underwent upper endoscopy and esophageal function tests, and took proton pump inhibitor (PPI) treatment. The prevalence of GERD and PPI efficacy was assessed and compared among patients with different dominant symptoms. RESULTS Altogether 374 patients (244 with predominantly esophageal symptoms and 130 with predominantly epigastric symptoms) were enrolled. Patients with predominantly epigastric symptoms had a slightly lower prevalence of reflux esophagitis and pathological acid reflux but a significantly lower PPI response rate than those with predominantly esophageal symptoms. Multivariable logistic regression analysis revealed that the predominant symptom was independently associated with PPI efficacy but could not predict the objective existence of GERD. GERD was objectively found in 136 patients, 30% of whom complained of predominantly epigastric symptoms and had similar reflux profiles and symptom outcomes as patients with predominantly esophageal symptoms. CONCLUSIONS Approximately 30% of patients with GERD complain of predominantly epigastric symptoms and have comparable reflux profiles and symptom outcomes as those with predominantly esophageal symptoms. Epigastric symptoms may be part of the diagnosis for GERD in a Chinese population. The study was registered with Clinicaltrials.gov (NCT02506634).

Background Supragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK. Methods We re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries. Results Impedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09–7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0–4.9)] compared to the UK [35% (0–54.1)] (P = 0.071). Conclusions The prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.

BACKGROUND We have previously shown, ex vivo, that alginate solutions can have a topical protective effect on oesophageal mucosal biopsies exposed to simulated gastric juice. Oesophageal mucosal impedance can measure the duration of mucosal adherence of ionic solutions since the impedance drops when the solution is present, and rises to baseline as the solution clears. AIM To investigate the in vivo duration of adhesion of swallowed alginate solution to distal oesophageal mucosa. METHODS We studied 20 healthy volunteers and 10 patients with heartburn. A pH-impedance catheter was inserted, and baseline distal channel oesophageal impedance measured. Healthy volunteers received 10 mL of either sodium alginate (Gaviscon Advance), Gaviscon placebo (no alginate) or viscous slurry (saline mixed with sucralose), given in a randomised, single-blinded order over three visits. Patients received either sodium alginate or placebo on two visits. Initial impedance drop was measured, then 1-minute mean impedance was measured each minute until ≥75% recovery to baseline. RESULTS In healthy volunteers, sodium alginate adhered to the oesophageal mucosa for longer than placebo or viscous slurry (10.4 [8.7] minutes vs 1.1 [1.6] vs 3.6 [4.0], P

Background/Aims Mean nocturnal baseline impedance (MNBI) during multichannel intraluminal impedance pH-monitoring (MII-pH) reflects the status of esophageal mucosal integrity. MNBI is suggested as an adjunctive method to distinguish patients with true gastroesophageal reflux disease (GERD) from functional heartburn (FH) and might predict outcomes for anti-reflux treatment. However, current methodology for calculation of MNBI is time-consuming and subject to operator-dependent selection bias. We aim to simplify and provide a more objective method to calculate MNBI. Methods We retrospectively analyzed 100 MII-pH tracings from 20 patients with erosive reflux disease, 20 with non-erosive reflux disease (NERD), 20 with reflux hypersensitivity, 20 with functional heartburn (FH), and 20 healthy asymptomatic volunteers. We compared the current “conventional” MNBI analysis with our “simple” MNBI analysis measured by selecting the whole supine period using the impedance average calculation function in the MII-pH software. Results Absolute values were very similar and there was a strong correlation between conventional and simple MNBI values in the most distal channel in all groups (r ≥ 0.8, P < 0.001) including patients with increased supine acid reflux. Distal esophageal simple MNBI negatively correlated with acid exposure time (r = -0.695, P < 0.001). Patients with erosive reflux disease and NERD had lower simple MNBI values in the most distal channel compared to other groups (P < 0.001). With a cutoff value of 1785 ohms, simple MNBI can discriminate patients with GERD from those with reflux hypersensitivity and FH (sensitivity 80.0% and specificity 89.7%). Conclusion Simple MNBI analysis provides very similar values and has an excellent correlation with conventional MNBI analysis. (J Neurogastroenterol Motil 2020;26:241-247)

Type 2 diabetes (T2DM) is associated with gastroesophageal reflux disease (GERD) in the general population, but the relationship between these conditions in candidates for bariatric surgery is uncertain. We compared the prevalence of GERD and the association between GERD symptoms and esophagitis among bariatric candidates with and without T2DM. Cross-sectional study of baseline data from the Oseberg study in Norway. Both groups underwent gastroduodenoscopy and completed validated questionnaires: Gastrointestinal Symptom Rating Scale and Gastroesophageal Reflux Disease Questionnaire. Participants with T2DM underwent 24-h pH-metry. A total of 124 patients with T2DM, 81 women, mean (SD) age 48.6 (9.4) years and BMI 42.3 (5.5) kg/m2, and 64 patients without T2DM, 46 women, age 43.0 (11.0) years and BMI 43.0 (5.0) kg/m2, were included. The proportions of patients reporting GERD-symptoms were low (

Objectives Up to 40% of children presenting with reflux symptoms do not respond to standard medical interventions. In adults, 20% of patients presenting with Proton Pump Inhibitors refractory Gastro-Esophageal Reflux Disease (GERD) have rumination syndrome. The management of GERD and rumination differ significantly. Our study aimed to identify rumination syndrome amongst children presenting with persistent GERD symptoms based on a distinct pattern on impedance-pH monitoring. Methods The parameters of impedance-pH monitoring were compared between children with rumination syndrome (n = 12), diagnosed on high-resolution manometry impedance (HRM/Z), children with GERD (n = 18), children with an alternative diagnosis (non-GERD, n = 12) and children negative for rumination based on HRM/Z (n = 14). The parameters that distinguish the rumination group were identified and incorporated into a scoring system, which was blindly applied on a separate group of children with refractory GERD (n = 18) to define its sensitivity and specificity. Results Rumination syndrome presents in 44% of children with refractory GERD. Children with rumination syndrome present with a large number of proximal reflux episodes (>57.5 episodes/24 hours); a high frequency of nonacid reflux events in the postprandial period (>2/hour); and a highly positive symptom-reflux association analysis (SAP ≥ 95%). A score of ≥2 out of the 3 points distinguishes children with rumination syndrome with 75% sensitivity and 80% specificity. Conclusions Children with rumination syndrome have a distinct pattern of impedance-pH monitoring and can be distinguished amongst children presenting with refractory GERD. Applying a simple scoring system during impedance-pH analysis could lead to early diagnosis of children with rumination syndrome.

OBJECTIVE: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. DESIGN: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. RESULTS: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. CONCLUSIONS: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.

Contains fulltext : 288010.pdf (Publisher’s version ) (Open Access) BACKGROUND: There are several options for the surgical management of GERD in adults. Previous guidelines and systematic reviews have compared the effects of total fundoplication versus pooled effects of different techniques of partial fundoplication. OBJECTIVE: To develop evidence-informed, trustworthy, pertinent recommendations on the use of total, posterior partial and anterior partial fundoplications for the management of GERD in adults. METHODS: We performed an update systematic review, network meta-analysis, and evidence appraisal using the GRADE and the Confidence in Network Meta-Analysis methodologies. An international, multidisciplinary panel of surgeons, gastroenterologists, and a patient representative reached unanimous consensus through an evidence-to-decision framework to select among multiple interventions, and a Delphi process to formulate the recommendation. The project was developed in an online authoring and publication platform (MAGICapp), and was overseen by an external auditor. RESULTS: We suggest posterior partial fundoplication over total posterior or anterior 90° fundoplication in adult patients with GERD. We suggest anterior >90° fundoplication as an alternative, although relevant comparative evidence is limited (weak recommendation). The guideline, with recommendations, evidence summaries and decision aids in user friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/j20X4n. CONCLUSION: This rapid guideline was developed in line with highest methodological standards and provides evidence-informed recommendations on the surgical management of GERD. It provides user-friendly decision aids to inform healthcare professionals' and patients' decision making. 01 november 2022

Increased SGB is currently more often recognized not only in patients with belching as a main symptom, but also in patients with reflux like symptoms that are refractory to PPI treatment or patients with reflux hypersensitivity. Detection of increased SGB during analysis of impedance-pHmetry can help to better understand the pathophysiology of symptoms in individual patients and to provide more focused and specific treatment. At the moment, the most efficient treatments for increased SGB are CBT and Speech therapies, pharmacological treatment being less effective and prone to mild secondary effects. In this issue of Neurogastroenterology and Motility, Punkinnen et al demonstrate, in controlled clinical trial, that behavioral therapy was superior to follow-up without intervention in patients with SGB. We present a critical review of the different treatment modalities currently available for patients with pathological SGB.

Gastroesophageal reflux (GOR) is defined as "the passage of gastric contents into the esophagus with or without regurgitation and vomiting" and gastroesophageal reflux disease (GORD) is defined "when GOR leads to troublesome symptoms affecting the daily functioning and/or complications." This definition was first developed in 2006 by the Montreal consensus group (1) and later on adopted by pediatric gastroenterology societies such as ESPGHAN and NASPGHAN in 2009 (2). The definition of gastroesophageal reflux reveals little about its pathophysiology and is focused on symptomatology. In this way, it acts as an umbrella term for the multifactorial causes of the disease and the various phenotypes encountered; from functional heartburn to hypersensitive esophagus and nonerosive reflux disease, to erosive esophagitis and Barrett's esophagus. This article is devoted to the pathophysiology of pediatric GORD in comparison to adult GORD and is divided in 2 parts. In the first part, we will systematically describe the different mechanisms for the generation and clearance of reflux events, while on the second part we will discuss the mechanisms involved in symptoms generation. Finally, we will discuss the similarities and differences between pediatric and adult GORD.

Gastro-oesophageal reflux disease (GERD) is a common disorder in adults and children. The global prevalence of GERD is high and increasing. Non-erosive reflux disease is the most common phenotype of GERD. Heartburn and regurgitation are considered classic symptoms but GERD may present with various atypical and extra-oesophageal manifestations. The pathophysiology of GERD is multifactorial and different mechanisms may result in GERD symptoms, including gastric composition and motility, anti-reflux barrier, refluxate characteristics, clearance mechanisms, mucosal integrity and symptom perception. In clinical practice, the diagnosis of GERD is commonly established on the basis of response to anti-reflux treatment; however, a more accurate diagnosis requires testing that includes upper gastrointestinal tract endoscopy and reflux monitoring. New techniques and new reflux testing parameters help to better phenotype the condition. In children, the diagnosis of GERD is primarily based on history and physical examination and treatment vary with age. Treatment in adults includes a combination of lifestyle modifications with pharmacological, endoscopic or surgical intervention. In refractory GERD, optimization of proton-pump inhibitor treatment should be attempted before a series of diagnostic tests to assess the patient's phenotype.

Background Recent studies reported that impaired proximal duodenal mucosa, assessed by duodenal biopsy, could play an important role in the development of dyspeptic symptoms. The aims of this study were (a) to develop a method to measure “in vivo” duodenal and jejunal baseline impedance (BI) and (b) to assess small bowel mucosal integrity in patients with functional dyspepsia (FD) and healthy controls (HC). Methods We recruited 16 patients with FD and 15 HC. All subjects underwent ambulatory duodeno-jejunal manometry combined with impedance (HRM/Z), BI were determined by measuring impedance immediately after the passage of nocturnal migrating motor complex (MMC) phase IIIs. Results The number of MMC phase IIIs in FD was significantly lower than that in HC (2.6 ± 1.4 vs 4.8 ± 1.7, p

Excessive belching is frequently reported in adult patients with gastro-oesophageal reflux disease (GORD) and dyspepsia. Although postprandial gastric belching (GB) is considered a physiological mechanism for gastric venting, supra-gastric belching (SGB) is considered a distinct behavioural disorder. We aimed to define the prevalence of different types of belching and its association with reflux disease in paediatric patients.We retrospectively analysed reflux monitoring studies from 287 patients (median age: 7.0 years; interquartile range 3.0-11.3 years) with a suspicion of GORD. Based on oesophageal acid exposure time (AET) patients were divided in 3 groups: (a) physiological AET, (b) borderline AET and (c) pathological AET. MII-pH studies were manually edited and reflux disease parameters were measured together with quantification of GB and SGB.Two hundred one children (70.0%) had physiological AET (median: 0.8; interquartile range 0.3-1.6), 52 (18.1%) had borderline AET (median: 4.2; interquartile range 3.4-5.3) and 34 (11.9%) had pathologic AET (median: 10.7; interquartile range 9.1-14.2). Gastric belching was observed in all studies. Gastric belching related reflux was more frequently observed in patients with borderline and pathological AET (p0.001). This was more common in older children. SGB were observed in only 7 (2.4%) children (age range: 8-17years) in our population and all patients had Physiological AET. Only 3 (1%) patients had pathological number of SGB (13/24 h).Gastric belching related reflux is observed in children with increased AET. SGB is very rare in the paediatric population.

Gastro-oesophageal reflux disease (GERD) is a common disorder in adults and children. The global prevalence of GERD is high and increasing. Non-erosive reflux disease is the most common phenotype of GERD. Heartburn and regurgitation are considered classic symptoms but GERD may present with various atypical and extra-oesophageal manifestations. The pathophysiology of GERD is multifactorial and different mechanisms may result in GERD symptoms, including gastric composition and motility, anti-reflux barrier, refluxate characteristics, clearance mechanisms, mucosal integrity and symptom perception. In clinical practice, the diagnosis of GERD is commonly established on the basis of response to anti-reflux treatment; however, a more accurate diagnosis requires testing that includes upper gastrointestinal tract endoscopy and reflux monitoring. New techniques and new reflux testing parameters help to better phenotype the condition. In children, the diagnosis of GERD is primarily based on history and physical examination and treatment vary with age. Treatment in adults includes a combination of lifestyle modifications with pharmacological, endoscopic or surgical intervention. In refractory GERD, optimization of proton-pump inhibitor treatment should be attempted before a series of diagnostic tests to assess the patient's phenotype.

Background Ineffective esophageal motility (IEM) is the most common motility disorder. However, little is known about its pathophysiology. Vagal afferent nerves convey esophageal intraluminal bolus information to solitary nucleus, which is likely to be involved with esophageal primary and secondary peristalsis (SP). We hypothesized that altered mucosal sensory afferents underlie the pathogenesis of IEM. Methods We prospectively collected esophageal biopsies from 38 patients with proton pump inhibitor-refractory reflux symptoms from January to December 2019. All patients underwent high-resolution manometry for the evaluation of primary and secondary peristalsis, and off-PPI 24-h impedance-pH studies. Biopsies were analyzed using immunohistochemistry for identification of calcitonin gene-related peptide-immunoreactive (CGRP-IR) nerves and qPCR for mRNA expression of potential mechanoreceptors. Key results Overall 32 patients were finally analyzed which consisted of 11 patients with normal motility and 21 patients with IEM. The position of mucosal CGRP-IR nerves from the esophageal lumen did not differ between the two groups (the proximal esophagus (p = 0.52), the mid-esophagus (p = 0.92), the distal esophagus (p = 0.29)) with the similar reflux profile. No difference was seen in the position of CGRP-IR nerves between patients with successful triggering of SP and those unable to trigger SP. There was also no difference in mRNA expression of each potential mechanoreceptors (TRPA1, TRPV1, TRPV4, ASIC1, ASIC3) between the two groups. Conclusions and inferences Our study showed that mucosal sensory afferents nerve position and mRNA expression of potential mechanoreceptors did not correlate to weak esophageal contraction.

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

Ambulatory pH-impedance monitoring evaluates gastroesophageal reflux disease (GERD) symptoms that persist despite empiric treatment trials.1 Although automated analysis of pH-impedance monitoring is known to overestimate non-acid reflux episodes,2 even experts may disagree on individual reflux episodes,3,4 and accurate identification of postreflux swallow-induced peristaltic wave (PSPW). We hypothesized that a formal consensus meeting between expert pH-impedance reviewers would establish definitive criteria for identification of reflux episodes and PSPW, and improve inter-reviewer variability.

Background Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited. Methods Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions. Results Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P < 0.001). 5(th) percentile EGJ-CI values ranged from 6.9 to 12.1 mm Hg cm. EGJ-CI values were consistent across world regions, but different between manufacturers even within the same world region (P = 0.3) but higher in women (P < 0.001). Conclusions EGJ morphology is predominantly type 1 in healthy adults. EGJ-CI varies widely in health, with significant gender influence, but is consistent within each HRM system. Manufacturer-specific normative values should be utilized for clinical HRM interpretation.

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.

Objective Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects. Design Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI). Results Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie. Conclusion Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings., Queen Mary University of London, UK [DDCH1A3R], The study was conducted with financial support from Research Grant DDCH1A3R, Queen Mary University of London, UK.

Introduction Esophageal mucosa innervation in adults with nonerosive reflux disease (NERD) is more superficial compared with healthy volunteers. We delineated the esophageal mucosal innervation in pediatric NERD and controls. Methods Distal and proximal pediatric esophageal biopsies were immunohistochemically stained with calcitonin gene-related peptide and transient receptor potential cation channel subfamily V member 1. Results Mucosal innervation was assessed in 18 controls (9M:9F, median age: 9 years) and 11 NERD patients (6M:5F, median age: 5 years). Calcitonin gene-related peptide positive nerve fibers were lying deep in the mucosa in both groups, P > 0.05 and did not coexpress transient receptor potential cation channel subfamily V member 1. Discussion The pediatric esophageal mucosa in NERD displays deep lying nerve fibers, in contrast to adults.

Hypercontractile esophagus (HE) is a heterogeneous major motility disorder diagnosed when ≥20% hypercontractile peristaltic sequences (distal contractile integral >8,000 mm Hg*s*cm) are present within the context of normal lower esophageal sphincter (LES) relaxation (integrated relaxation pressure < upper limit of normal) on esophageal high-resolution manometry (HRM). HE can manifest with dysphagia and chest pain, with unclear mechanisms of symptom generation. The pathophysiology of HE may entail an excessive cholinergic drive with temporal asynchrony of circular and longitudinal muscle contractions; provocative testing during HRM has also demonstrated abnormal inhibition. Hypercontractility can be limited to the esophageal body or can include the LES; rarely, the process is limited to the LES. Hypercontractility can sometimes be associated with esophagogastric junction (EGJ) outflow obstruction and increased muscle thickness. Provocative tests during HRM can increase detection of HE, reproduce symptoms, and predict delayed esophageal emptying. Regarding therapy, an empiric trial of a proton pump inhibitor, should be first considered, given the overlap with gastroesophageal reflux disease. Calcium channel blockers, nitrates, and phosphodiesterase inhibitors have been used to reduce contraction vigor but with suboptimal symptomatic response. Endoscopic treatment with botulinum toxin injection or pneumatic dilation is associated with variable response. Per-oral endoscopic myotomy may be superior to laparoscopic Heller myotomy in relieving dysphagia, but available data are scant. The presence of EGJ outflow obstruction in HE discriminates a subset of patients who may benefit from endoscopic treatment targeting the EGJ.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ. © 2020 John Wiley & Sons Ltd, National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK: P01 DK092217, National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Number: P01 DK092217

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.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.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).BI calculation can be automated using AI. Novel AI metrics show potential in predicting GERD treatment outcome.