Project description:Esophageal biopsy RNA was isolated from proximal esophageal biopsied RNA from patients with EoE-like inflammatory diseases (EoE-like esophagitis, lymphocytic esophagitis, non-specific esophagitis), patients with active EoE, patients with GERD, and unaffected healthy controls. EoE-like inflammatory disease patients were clinically active at the time when biopsies were taken. None of the patients (EoE-like inflammatory diseases, EoE, GERD and controls) were under anti-eosinophil treatment (including dietary restrictions). The quality of the RNA-seq data was assessed using fastqc v. 0.11.5 1) and RSeQC v. 2.6.4 2). The reads were mapped to the reference genome using HiSat2 v. 2.1.0 3). FeatureCounts v. 1.6.0 4) was used to count the number of reads overlapping with each gene as specified in the genome annotation (Homo_sapiens.GRCh38.94). The Bioconducture package DESeq2 5) was used to test for differential gene expression between the experimental groups. TopGo 6) was used to identify gene ontology terms containing unusually many differentially expressed genes. An interactive Shiny application was set up to facilitate the exploration and visualisation of the RNA-seq results. All analyses were run in R version 3.4.4 (2018-03-15)
Project description:Background & aimsIt is not clear how age affects airway protective mechanisms. We investigated the effects of aging on upper esophageal sphincter (UES) and esophageal body pressure responses to slow and ultraslow simulated reflux events and post-reflux residue.MethodsWe performed a prospective study of 11 elderly (74 ± 9 years old) and 11 young (28 ± 7 years old) healthy volunteers. Participants were placed in a supine position and evaluated by concurrent high-resolution impedance manometry and an esophageal infusion technique. Potential conditions of gastroesophageal reflux were simulated, via infusion of 0.1 N HCl and saline. UES and esophageal pressure responses were measured during the following: slow infusion (1 mL/s) for 60 seconds, 60 seconds of postinfusion dwell period, ultraslow infusion (0.05 mL/s) for 60 seconds, and 60 seconds of a postinfusion dwell period. All infusions were repeated 3 times. We used the UES high-pressure zone contractile integral (UES-CI) to determine responses of the UES.ResultsYoung and elderly subjects each had a significant increase in the UES-CI during slow infusions and during entire passive dwell intervals compared with baseline (P < .01, both groups). Ultraslow infusions were associated with a significant increase in UES-CI in only the young group, in the late infusion period, and into the dwell interval (P < .01). During the slow infusions and their associated dwell periods, young subjects had a higher frequency of secondary peristalsis than elderly subjects (P < .05). There was more secondary peristalsis during active infusions than dwell intervals. Secondary peristalsis was scarce during ultraslow infusions in both groups.ConclusionsUES and esophageal body pressure responses to low-volume ultraslow reflux and associated post-reflux residue are reduced in elderly individuals. This deterioration could have negative effects on airway protection for people in this age group.
Project description:The upper esophageal sphincter (UES) reflexively responds to bolus presence within the esophageal lumen, therefore UES metrics can vary in achalasia. Within consecutive patients undergoing esophageal high-resolution manometry (HRM), 302 patients (58.2±1.0 year, 57% F) with esophageal outflow obstruction were identified, and compared to 16 asymptomatic controls (27.7±0.7 year, 56% F). Esophageal outflow obstruction was segregated into achalasia subtypes 1, 2, and 3, and esophagogastric junction outflow obstruction (EGJOO with intact peristalsis) using Chicago Classification v3.0. UES and lower esophageal sphincter (LES) metrics were compared between esophageal outflow obstruction and normal controls using univariate and multivariate analysis. Linear regression excluded multicollinearity of pressure metrics that demonstrated significant differences across individual subtype comparisons. LES integrated relaxation pressure (IRP) had utility in differentiating achalasia from controls (P<.0001), but no utility in segregating between subtypes (P=.27). In comparison to controls, patients collectively demonstrated univariate differences in UES mean basal pressure, relaxation time to nadir, recovery time, and residual pressure (UES-RP) (P≤.049). UES-RP was highest in type 2 achalasia (P<.0001 compared to other subtypes and controls). In multivariate analysis, only UES-RP retained significance in comparison between each of the subgroups (P≤.02 for each comparison). Intrabolus pressure was highest in type 3 achalasia; this demonstrated significant differences across some but not all subtype comparisons. Nadir UES-RP can differentiate achalasia subtypes within the esophageal outflow obstruction spectrum, with highest values in type 2 achalasia. This metric likely represents a surrogate marker for esophageal pressurization.
Project description:ObjectiveThe microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis.DesignIn this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease.ResultsSamples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects.ConclusionsDiseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.
Project description:RationaleBotulinum toxin injection is a widely used procedure for the treatment of the dysfunction of the upper esophageal sphincter (UES). Although the injection can be guided by ultrasound, electromyography, or computed tomography, such techniques cannot determine the exact extent of narrowed UES and ensure that the narrowed extent is fully covered by the treatment. This report describes a dual guiding technique with ultrasound and the balloon catheter in a patient with poststroke dysphagia to improve these weaknesses.Patient concernsThe patient was admitted to a rehabilitation hospital 2 weeks postcerebral infarction.DiagnosesClinical presentation of the patient included severe hemiplegia and dysphagia. The fiberoptic endoscopic evaluation of swallowing (FEES) revealed penetration/aspiration when swallowing 1 ml water and 1 ml yogurt and pooling in the postcricoid region.InterventionsBalloon catheter dilatation procedures and Botulinum toxin injection were performed. We used a dual guiding technique with ultrasound and the balloon catheter to determine the whole segment of UES dysfunction by locating the lowest level of the impaired UES opening and to reduce difficulty in differentiating UES from adjacent tissues during Botulinum toxin injection.OutcomesNo persistent progress was observed on the symptoms and volume of the balloon during dilatation. The patient showed quick responses after Botulinum toxin injection. The postinjection balloon catheter dilatation showed an increased maximum volume (preinjection, 5.5 ml vs. postinjection, 14 ml), and the patient was able to eat yogurt, congee, or semi-solid food 100-150 ml 4 weeks after the injection.LessonsThe dual guiding method holds several advantages, suggesting that it may be considered as a promising choice in dealing with UES dysfunction.
Project description:BackgroundThe Reflux Band, an external upper esophageal sphincter (UES) compression device, reduces esophago-pharyngeal reflux events. This study aimed to assess device efficacy as an adjunct to proton pump inhibitor (PPI) therapy in patients with laryngopharyngeal reflux (LPR).MethodsThis two-phase prospective clinical trial enrolled adults with at least 8 weeks of laryngeal symptoms (sore throat, throat clearing, dysphonia) not using PPI therapy at two tertiary care centers over 26 months. Participants used double dose PPI for 4 weeks in Phase 1 and the external UES compression device nightly along with PPI for 4 weeks in Phase 2. Questionnaire scores and salivary pepsin concentration were measured throughout the study. The primary endpoint of symptom response was defined as reflux symptom index (RSI) score ≤ 13 and/or > 50% reduction in RSI.ResultsThirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m2 (5.1). Primary endpoint was met in 11 (35%) participants after Phase 1 (PPI alone) and 17 (55%) after Phase 2 (Device + PPI). Compared to baseline, mean RSI score (24.1 (10.9)) decreased at end of Phase 1 (PPI alone) (21.9 (9.7); p = 0.06) and significantly decreased at end of Phase 2 (Device + PPI) (15.5 (10.3); p < 0.01). Compared to non-responders, responders to Device + PPI had a significantly lower BMI (p = 0.02) and higher salivary pepsin concentration (p = 0.01).ConclusionThis clinical trial highlights the potential efficacy of the external UES compression device (Reflux Band) as an adjunct to PPI for patients with LPR (ClinicalTrials.Gov NCT03619811).
Project description:Reflux-associated laryngeal symptoms (RALS) is the process in which chronic laryngeal symptoms are related to gastroesophagopharyngeal reflux.1 Impairment of upper esophageal sphincter (UES) reflexes may predispose to esophagopharyngeal reflux.1 The novel noninvasive nonpharmacologic UES assist device (UESAD) applies external cricoid pressure to augment intraluminal UES pressure by 20 to 30 mm Hg and reduce esophagopharyngeal reflux events.2 This study aimed to assess the therapeutic efficacy of the UESAD in a pragmatic clinical setting, and to identify factors associated with symptom response among patients with suspected RALS.
Project description:BackgroundEosinophilic esophagitis (EoE) is a clinicopathologic disorder first described in 1978 which has gained significant recognition over the past 10 years. Numerous prevalence studies have been performed around the globe, both in pediatric and adult populations documenting a prevalence between 0.002% and 6.5%. The aim of this study is to assess the utility of routinely screening for EoE in patients with dysphagia.MethodsA prospective, observational study in which adult patients with a complaint of esophageal dysphagia were enrolled.ResultsOf the 135 patients enrolled, 122 completed the study; 100 patients had nonobstructive dysphagia, while 22 patients had a luminal finding which could explain their dysphagia. The prevalence of EoE in the nonobstructive dysphagia group was 22% (95% CI: 13.9-30.1%); 32.7% of male patients with nonobstructive dysphagia were found to have EoE compared with 8.9% of females (p = 0.004). The mean age of nonobstructive patients found to have EoE was 37.8 years. White patients with nonobstructive dysphagia were found to have a 25.9% prevalence of EoE, compared with 0% of African Americans, 0% of Asians, and 14.3% of Hispanics. When comparing Whites with non-Whites, the prevalence of EoE was noted to be 25.9% versus 5.3%, respectively (p = 0.050).ConclusionsEoE is a common cause of nonobstructive dysphagia. We believe that the high prevalence of EoE in patients with nonobstructive dysphagia supports the practice of routine biopsies to screen for the presence of abnormally high numbers of eosinophils in this subgroup.
Project description:Surgical intervention for gastroesophageal reflux disease (GERD) has historically been limited to fundoplication. Magnetic sphincter augmentation (MSA) is a less invasive alternative that was introduced 15 years ago, and it may have a superior side-effect profile. To date, however, there has been just a single published study reporting outcomes in a UK population. This study reports quality-of-life (QOL) outcomes and antacid use in patients undergoing MSA, with a particular focus on postoperative symptoms and those with severe reflux. A single-center cohort study was carried out to assess the QOL outcomes and report long-term safety outcomes in patients undergoing MSA. GERD-health-related quality of life (GERD-HRQL) and Reflux Symptom Index (RSI) scores were collected preoperatively, and immediately postoperatively, at 1-, 2-, 3-, and 5-year follow-up time points. All patients underwent preoperative esophagogastroduodenoscopy, impedance, and manometry. Two hundred and two patients underwent laparoscopic MSA over 9 years. The median preoperative GERD-HRQL score was 31, and the median RSI score was 17. There was a reduction in all scores from preoperative values to each time point, which was sustained at 5-year follow-up; 13% of patients had a preoperative DeMeester score of >50, and their median preoperative GERD-HRQL and RSI scores were 32 and 15.5, respectively. These were reduced to 0 at the most recent follow-up. There was a significant reduction in antacid use at all postoperative time points. Postoperative dilatation was necessary in 7.4% of patients, and the device was removed in 1.4%. Erosion occurred in no patients. MSA is safe and effective at reducing symptom burden and improving QOL scores in patients with both esophageal and laryngopharyngeal symptoms, including those with severe reflux.