In Obesity, Esophagogastric Junction Fat Impairs Esophageal Barrier Function and Dilates Intercellular Spaces via HIF-2α.

Background & Aims: Dilated intercellular space (DIS) in esophageal epithelium, a sign of impaired barrier function, is a characteristic finding of GERD that also is found in obese patients without GERD. We have explored molecular mechanisms whereby adipose tissue products might impair esophageal barrier integrity.

Methods: We established cultures of visceral fat obtained during foregut surgery from obese and non-obese patients.

Identification of novel immune cell signature in gastroesophageal reflux disease: altered mucosal mast cells and dendritic cell profile.

Introduction: Heartburn pathogenesis in GERD remains incompletely understood. We aimed to identify differences in the immune cell signature and sensory mucosal markers between reflux phenotypes and healthy asymptomatic subjects.

Methods: Thirty-seven patients with heartburn symptoms were phenotyped endoscopically and with objective reflux studies into erosive reflux disease (ERD) (N=10), nonerosive reflux disease (NERD) (N=9), functional heartburn (FH) (N=9), and Barrett's esophagus (BO) (N=9).

Superficial oesophageal mucosal innervation may contribute to severity of symptoms in oesophageal motility disorders.

Background: Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role.

Aims: To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders.

Methods: We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained.

Sensory Phenotype of the Oesophageal Mucosa in Gastro-Oesophageal Reflux Disease.

Gastroesophageal reflux disease (GORD) affects up to 20% of Western populations, yet sensory mechanisms underlying heartburn pathogenesis remain incompletely understood. While central mechanisms of heartburn perception have been established in earlier studies, recent studies have highlighted an important role of neurochemical, inflammatory, and cellular changes occurring in the oesophageal mucosa itself. The localization and neurochemical characterisation of sensory afferent nerve endings differ among GORD phenotypes, and could explain symptom heterogeneity among patients who are exposed to similar levels of reflux.

Randomised clinical trial: the use of alginates during preinvestigation proton pump inhibitor wash-out and their impact on compliance and symptom burden.

Background/aims: Investigation of gastro-oesophageal reflux disease is usually performed off proton pump inhibitors (PPIs). This can exacerbate symptoms, potentially impacting investigation accuracy if patients circumvent the preinvestigation instructions. There are no standard recommendations on how to manage PPI withdrawal.

Clonal Transitions and Phenotypic Evolution in Barrett's Esophagus.

Background & Aims: Barrett's esophagus (BE) is a risk factor for esophageal adenocarcinoma but our understanding of how it evolves is poorly understood. We investigated BE gland phenotype distribution, the clonal nature of phenotypic change, and how phenotypic diversity plays a role in progression.

Methods: Using immunohistochemistry and histology, we analyzed the distribution and the diversity of gland phenotype between and within biopsy specimens from patients with nondysplastic BE and those who had progressed to dysplasia or had developed postesophagectomy BE.

A distributed optimisation framework combining natural gradient with Hessian-free for discriminative sequence training.

This paper presents a novel natural gradient and Hessian-free (NGHF) optimisation framework for neural network training that can operate efficiently in a distributed manner. It relies on the linear conjugate gradient (CG) algorithm to combine the natural gradient (NG) method with local curvature information from Hessian-free (HF). A solution to a numerical issue in CG allows effective parameter updates to be generated with far fewer CG iterations than usually used (e.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

Background: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments.

Objective: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE.

Combination of deep speaker embeddings for diarisation.

Significant progress has recently been made in speaker diarisation after the introduction of d-vectors as speaker embeddings extracted from neural network (NN) speaker classifiers for clustering speech segments. To extract better-performing and more robust speaker embeddings, this paper proposes a c-vector method by combining multiple sets of complementary d-vectors derived from systems with different NN components. Three structures are used to implement the c-vectors, namely 2D self-attentive, gated additive, and bilinear pooling structures, relying on attention mechanisms, a gating mechanism, and a low-rank bilinear pooling mechanism respectively.

Esophageal Mucosa Innervation in Children With Nonerosive Reflux Disease.

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.

Esophageal afferent innervation and its role in gastro-esophageal reflux disease symptoms.

Purpose Of Review: Despite the wide prevalence of gastro-esophageal reflux disease (GERD), the neurophysiological mechanisms underlying heartburn perception in the esophagus of patients with GERD remains incompletely understood. Recent studies have highlighted the potential influence sensory afferent nerves innervating the oesophageal epithelium may have on heartburn pathogenesis. The purpose of this review is to consider the current understanding of esophageal afferent neuronal innervation, including the nociceptive role of acid-sensing receptors expressed on these sensory nerves, in relation to pain perception in the esophagus of GERD patients.

Heartburn sensation in nonerosive reflux disease: pattern of superficial sensory nerves expressing TRPV1 and epithelial cells expressing ASIC3 receptors.

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.

Changes in UK medical trainees' perceptions of workplace-based assessments across 10 years: results from two cross-sectional studies.

Objectives: Workplace-based assessments (WPBAs) have become embedded in the training and assessment of UK medical trainees since the onset of the 21st century. When first introduced WPBA required a significant adjustment in both trainees' and educators' training behaviour, and was met with scepticism in some quarters. In this study, we aimed to evaluate how trainees' perceptions of WPBAs have evolved over a 10-year period, as experience with them has increased.

Mucosal pathogenesis in gastro-esophageal reflux disease.

Background: Despite gastro-esophageal reflux disease affecting up to 20% of Western populations, relatively little is known about the molecular mechanisms underlying its most troublesome symptom: heartburn. Recent findings have unveiled the role of components of the esophageal mucosa in the pathogenesis of GERD including sensory nociceptive nerves and inflammatory mediators. Erosive esophagitis was long believed to develop as a result of acid injury at the esophageal lumen, but novel concepts suggest the generation of reflux-induced esophageal injury as a result of cytokine-mediated inflammation.

Duration of adhesion of swallowed alginates to distal oesophageal mucosa: implications for topical therapy of oesophageal diseases.

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.

Identification of Different Phenotypes of Esophageal Reflux Hypersensitivity and Implications for Treatment.

Background & Aims: Reflux hypersensitivity (RH), a functional esophageal disorder, is detected in 14%-20% of patients who present with typical esophageal symptoms. As many as 40% of patients with RH do not respond to treatment with pain modulators or proton pump inhibitors (PPIs); behavior disorders might contribute to lack of treatment efficacy. We aimed to assess the prevalence of behavioral disorders and their effects on typical reflux symptoms in patients with RH.

Measurement of Esophageal Nocturnal Baseline Impedance: A Simplified Method.

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.

Rumination Syndrome in Children Presenting With Refractory Gastroesophageal Reflux Symptoms.

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.

Exacerbation of gastroesophageal reflux symptoms after discontinuation of proton pump inhibitors is not associated with increased esophageal acid exposure.

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.

Cashew gum, a biopolymer, topically protects oesophageal mucosa in non erosive reflux disease: A promising translational study.

This study aimed to investigate a standardized biopolymer, cashew gum (CG), in human oesophageal mucosa and mice with experimentally-induced non-erosive reflux disease (NERD). Human oesophageal biopsies from NERD patients were collected to evaluate the mucosal protection of CG through transepithelial electrical resistance (TER), mucosal permeability, and mucoadhesiveness tests. A surgical model of NERD in mice was induced, and barrier functions followed by suggestive oesophageal inflammatory hallmarks were evaluated.

Patients with dyspepsia have impaired mucosal integrity both in the duodenum and jejunum: in vivo assessment of small bowel mucosal integrity using baseline impedance.

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.

Persistent Postprandial Regurgitation vs Rumination in Patients With Refractory Gastroesophageal Reflux Disease Symptoms: Identification of a Distinct Rumination Pattern Using Ambulatory Impedance-pH Monitoring.

Objectives: Up to 20% of patients with refractory gastroesophageal reflux disease (GERD) might have postprandial rumination. The aim of this study was to distinguish persistent GERD-related postprandial regurgitation from rumination in patients with refractory GERD undergoing ambulatory multichannel intraluminal impedance-pH (MII-pH) monitoring.

Methods: We first characterized 24-hour and postprandial MII-pH patterns in 28 consecutive patients with confirmed rumination syndrome (positive clinical and high-resolution manometry/impedance).