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Patients with diffuse cutaneous systemic sclerosis (dcSSc) display a complex clinical phenotype. Transcriptional profiling of whole blood or tissue from patients are affected by changes in cellular composition that drive gene expression and an inability to detect minority cell populations. Here, we focused on the two main subtypes of circulating monocytes, classical (CM) and non-classical (NCM).SSc patients were recruited from the Prospective Registry for Early SSc registry. Clinical data were collected as well as peripheral blood for isolation of CM and NCM. Age-, sex-, and race-matched healthy volunteers were recruited as controls. Bulk macrophages were isolated from skin in a separate cohort. All samples were assayed by RNA-seq.We used an unbiased approach to cluster patients into three groups (A-C) based on their transcriptional signatures of CM relative to controls. Further, each group maintained their characteristic transcriptional signature in NCM. Genes upregulated in Group C demonstrated the highest signature compared to the other groups in skin macrophages. Patients from Group B and C exhibited worse lung function than Group A, although there was no difference in skin disease at baseline. We validated our approach by applying our group classifications to published bulk monocyte RNA-seq data on SSc patients: we found that patients with no skin disease were most likely to be classified as Group A.We are the first to show that transcriptional signature of CM and NCM can be used to unbiasedly stratify SSc patients and correlate with disease activity outcome measures.

La enfermedad por reflujo gastroesofágico (ERGE) es sumamente prevalente en nuestro medio. Sus síntomas son variados y los mecanismos fisiopatológicos son múltiples. Por lo tanto, el diagnóstico de esta entidad suele ser complejo. Han sido descriptos una serie de métodos diagnósticos. No obstante, el patrón de oro continúa siendo el tiempo de exposición ácida, medido durante el monitoreo ambulatorio de reflujo a través de pH-metría. El objetivo de este primer consenso latinoamericano fue evaluar críticamente, sobre la base de las mejores evidencias disponibles a la fecha, los diferentes métodos diagnósticos propuestos para la ERGE y emitir recomendaciones consensuadas luego de la discusión entre un grupo de expertos y una votación. Este consenso fue desarrollado por un grupo de expertos a partir de una búsqueda sistemática de la literatura y utilizando la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) para la evaluación de la calidad de la evidencia y la decisión de la fuerza de recomendación. Se emitieron recomendaciones en cuanto a la utilidad de diferentes métodos diagnósticos en relación con la ERGE.

BACKGROUND & AIMS: This study aimed to assess the accuracy of functional luminal imaging probe (FLIP) Panometry to detect esophagogastric junction (EGJ) obstruction assigned by high-resolution manometry (HRM) and the Chicago Classification version 4.0 (CCv4.0). METHODS: 687 adult patients that completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers (“controls”) were included. EGJ opening was evaluated with 16-cm FLIP during sedated endoscopy via EGJ-distensibility index (DI) and maximum EGJ diameter. HRM was classified according to CCv4.0 and focused on studies with a conclusive disorder of EGJ outflow (i.e. achalasia subtypes I, II, or III; or EGJ outflow obstruction with abnormal timed barium esophagram) or normal EGJ outflow. RESULTS: All 35 controls had EGJ-DI >3.0mm(2)/mmHg and maximum EGJ diameter >16mm. Per HRM and CCv4.0, 245 patients had a conclusive disorder of EGJ outflow and 314 patients had normal EGJ outflow. Among the 241 patients with reduced EGJ opening (REO: EGJ-DI

BACKGROUND & AIMS: Functional luminal imaging probe (FLIP) Panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP Panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS: 539 adult patients that completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. 35 asymptomatic volunteers (“controls”) and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response to distension (i.e. secondary peristalsis) were evaluated with 16-cm FLIP performed during sedated endoscopy and analyzed using a customize software program. HRM was classified according to CCv4.0. RESULTS: In the primary analysis, 156 patients (29%) had normal motility on FLIP Panometry, defined by normal EGJ opening (NEO) and a normal or borderline contractile response; 95% of these patients had normal motility or ineffective esophageal motility on HRM. 202 patients (37%) had obstruction with weak contractile response, defined as reduced EGJ opening and absent contractile response or impaired/disordered contractile response, on FLIP Panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. CONCLUSIONS: Classifying esophageal motility in response to sustained distension with FLIP Panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP Panometry provides a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.

Background & Aims Patient symptom reporting often does not correlate with the pathophysiological markers of esophageal disease, including eosinophilic esophagitis (EoE). Esophageal hypervigilance and symptom-specific anxiety are emerging as important considerations in understanding symptom reporting. As such, we aimed to conduct the first study of these constructs in EoE. Methods A retrospective review of an EoE patient registry was conducted and included eosinophils per high power field (from esophagogastroduodenoscopy biopsy: proximal, distal), endoscopic reference score, distal distensibility plateau (functional luminal imaging probe), Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, Northwestern Esophageal Quality of Life scale, and the Esophageal Hypervigilance and Anxiety Scale. Correlational and regression analyses evaluated relationships of hypervigilance and anxiety with Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, and Northwestern Esophageal Quality of Life scale when controlling for histology and endoscopic severity. Results One hundred and three patients had complete data, 69.9% were male, and the mean (SD) age was 40.66 (13.85) years. Forty-one percent had elevated dysphagia and 46% had elevated hypervigilance and anxiety. Esophageal symptom–specific anxiety emerged as the most important predictor of Brief Esophageal Dysphagia Questionnaire severity (44.8% of the variance), Visual Dysphagia Question of EoE Activity Index severity (26%), and poor health-related quality of life (HRQoL) (55.3%). Hypervigilance was also important, but to a lesser extent. Pathophysiological variables did not significantly predict symptoms or HRQoL. Recent food impaction can predict symptom-specific anxiety and proton pump inhibitor use can reduce hypervigilance. Conclusions Hypervigilance and symptom-specific anxiety are important for our understanding of self-reported patient outcomes in EoE. These processes outweigh endoscopic and histologic markers of EoE disease activity across dysphagia, difficulty eating, and HRQoL. Clinicians should assess hypervigilance and anxiety, especially in patients with refractory symptoms and poor HRQoL.

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.

INTRODUCTION: The functional luminal imaging probe (FLIP) is a novel catheter-based device that measures esophagogastric junction (EGJ) distensibility index (DI) in real-time. Previous studies have demonstrated DI to be a predictor of post-treatment clinical outcomes in patients with achalasia. We sought to evaluate EGJ DI in patients with achalasia before, during and after per-oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) and to assess the correlation of DI with postoperative outcomes. METHODS: DI (defined as the minimum cross-sectional area at the EGJ divided by distensive pressure) was measured at four time points in patients undergoing surgical myotomy for achalasia: 1) during outpatient preoperative endoscopy (preoperative DI), 2) at the start of each operation after the induction of anesthesia (induction DI), 3) at the conclusion of each operation (post-myotomy DI), and 4) at routine follow-up endoscopy 12 months postoperatively (follow-up DI). Routine Eckardt symptom score, endoscopy, timed barium esophagram, and pH study were obtained 12 months postoperatively. RESULTS: Forty-six patients (35 POEM, 11 LHM) underwent FLIP measurements at all four time points. Preop and induction mean DI were similar for both groups (POEM: 1 vs. 0.9 and LHM: 1.7 vs. 1.5 mm(2)/mmHg). POEM resulted in a significant increase in DI (induction 0.9 vs. post-myotomy 7 mm(2)/mmHg, p

Introduction High-resolution manometry (HRM) is generally considered the primary method to evaluate esophageal motility; functional luminal imaging probe (FLIP) panometry represents a novel method to do so and is completed during sedated endoscopy. This study aimed to compare HRM and FLIP panometry in predicting esophageal retention on timed barium esophagram (TBE). Methods A total of 329 adult patients who completed FLIP, HRM, and TBE for primary esophageal motility evaluation were included. An abnormal TBE was defined by a 1-minute column height >5 cm or impaction of a 12.5-mm barium tablet. The integrated relaxation pressure (IRP) on HRM was assessed in the supine and upright patient positions. Esophagogastric junction (EGJ) opening was evaluated with 16-cm FLIP performed during sedated endoscopy through EGJ-distensibility index and maximum EGJ diameter. Results Receiver operating characteristic curves to identify an abnormal TBE demonstrated AUC (95% confidence interval) of 0.79 (0.75-0.84) for supine IRP, 0.79 (0.76-0.86) for upright IRP, 0.84 (0.79-0.88) for EGJ-distensibility index, and 0.88 (0.85-0.92) for maximum EGJ diameter. Logistic regression to predict abnormal TBE showed odds ratios (95% confidence interval) of 1.8 (0.84-3.7) for consistent IRP elevation and 39.7 (16.4-96.2) for reduced EGJ opening on FLIP panometry. Of 40 patients with HRM-FLIP panometry discordance, HRM-IRP was consistent with TBE in 23% while FLIP panometry was consistent with TBE in 78%. Discussion FLIP panometry provided superior detection of esophageal retention over IRP on HRM. However, application of a complementary evaluation involving FLIP panometry, HRM, and TBE may be necessary to accurately diagnose esophageal motility disorders.

Achalasia is a debilitating major motor disorder of the oesophagus. Hypervigilance and symptom-specific anxiety substantially impact dysphagia symptom reporting, and quality of life is a critical patient outcome. Earlier achalasia symptom scales did not consider these constructs in their psychometric development.To develop a new symptom measure, the Achalasia Patient-Reported Outcomes (APRO) Questionnaire METHODS: Four gastroenterologists with achalasia expertise generated preliminary items. Patients reviewed items via cognitive interviews. Patients undergoing high-resolution manometry completed the APRO with Oesophageal Hypervigilance and Anxiety Scale, Northwestern Oesophageal Quality of Life Scale, and three measures of reflux and dysphagia. Full APRO psychometric assessment (reliability, validity, factor structure) was done. Cluster analysis evaluated APRO + symptom-anxiety/hypervigilance patient phenotypes.We included 961 patients with normal motility and 296 with achalasia. The APRO yielded three subscales: dysphagia, reflux, chest pain with two items for weight change and diet modifications. Reliability and validity were excellent. Twenty-five percent of achalasia patients may have high levels of anxiety/hypervigilance despite low symptoms, while 8% may report severe symptoms with low anxiety/hypervigilance. The APRO significantly predicted quality of life, but less cognitive-affective processes.The APRO is a reliable and valid measure of achalasia symptoms that addresses the limitations of existing questionnaires. Symptom anxiety and hypervigilance moderate the relationship between APRO and quality of life; 33% of patients with achalasia exhibit concerning patterns in symptom severity, anxiety and hypervigilance that may contribute to poorer outcomes.

The esophagogastric junction (EGJ) is located at the distal end of the esophagus and acts as a valve allowing swallowed food to enter the stomach and preventing acid reflux. Irregular weakening or stiffening of the EGJ muscles results in changes to its opening and closing patterns which can progress into esophageal disorders. Therefore, understanding the physics of the opening and closing cycle of the EGJ can provide mechanistic insights into its function and can help identify the underlying conditions that cause its dysfunction. Using clinical functional lumen imaging probe (FLIP) data, we plotted the pressure-cross-sectional area loops at the EGJ location and distinguished two major loop types – a pressure dominant loop (PDL) and a tone dominant loop (TDL). In this study, we aimed to identify the key characteristics that define each loop type and determine what causes the inversion from one loop to another. To do so, the clinical observations are reproduced using 1D simulations of flow inside a FLIP device located in the esophagus, and the work done by the EGJ wall over time is calculated. This work is decomposed into active and passive components, which reveal the competing mechanisms that dictate the loop type. These mechanisms are esophagus stiffness, fluid viscosity, and the EGJ relaxation pattern.

Optimal ambulatory reflux monitoring methodology in symptomatic reflux patients continues to be debated.To utilise published literature and expert opinion to develop recommendation statements addressing use of ambulatory reflux monitoring in clinical practice METHODS: The RAND Appropriateness Method (RAM) was utilised among 17 experts with discussion, revision and two rounds of ranking of recommendation statements. Ambulatory reflux monitoring protocol, methodology and thresholds ranked as appropriate by ≥80% of panellists met the criteria for appropriateness.Prolonged (96-h recommended) wireless pH monitoring off proton pump inhibitor (PPI) was identified as the appropriate diagnostic tool to assess the need for acid suppression in patients with unproven gastro-oesophageal reflux disease (GERD) and persisting typical reflux symptoms despite once-daily PPI. Acid exposure time (AET)4.0% on all days of monitoring with negative reflux-symptom association excludes GERD and does not support ongoing PPI treatment. Conversely, AET6.0% across ≥2 days is conclusive evidence for GERD and supports treatment for GERD, while AET10% across ≥2 days identifies severe acid burden that supports escalation of anti-reflux treatment. In previously proven GERD, impedance-pH monitoring on PPI is helpful in defining refractory GERD and mechanisms of continued symptoms; the presence of40 reflux events, AET 2.0% and a negative reflux-symptom association does not support escalation of anti-reflux treatment. In contrast, AET 4.0% and positive reflux-symptom association support escalation of anti-reflux treatment, including use of invasive therapeutics.Statements meeting appropriateness for average clinical care have been identified when utilising reflux monitoring in patients with typical reflux symptoms and PPI non-response.

Background The 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). Methods This 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. Results Thirty-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

The Chicago Classification (CC) is a dynamic, evolving classification scheme created by a diverse group of international esophageal experts. Its application has transformed the way esophageal motor data are used to define motility disorders, each iteration seeking to advance, simplify, and standardize the way clinicians worldwide diagnose esophageal dysmotility. The most recent update, CC version 4.0 (CCv4.0), emphasizes the importance of clinical context and distinguishes clinically relevant, conclusive manometric diagnoses from irrelevant manometric observations. Future iterations of CC may refine the classification of spastic esophageal disorders and incorporate machine learning and physics-based modeling to improve metrics.

OBJECTIVE: We aim to describe the long-term follow up data from our institution’s POEM experience. SUMMARY BACKGROUND DATA: Per-oral endoscopic myotomy (POEM) is a well-established endoscopic therapy for achalasia with excellent short-term efficacy, but long-term outcomes data are limited. METHODS: Patients greater than 4 years removed from POEM for treatment of achalasia were studied. Clinical success was defined as an Eckardt Symptom (ES) score ≤ 3 and freedom from reintervention for achalasia. Patients underwent esophagogastroduodenoscopy (EGD), high-resolution manometry, impedance planimetry, and timed barium esophagram (TBE) pre-operatively and at least 4 years post-operatively. Objective GERD was defined LA Grade B or worse esophagitis on EGD. RESULTS: One hundred and nineteen consecutive patients were included. Five patients died or had catastrophic events unrelated to achalasia or POEM. One hundred of the remaining patients (88%, 100/114) had long-term data available. Clinical follow up for all patients was greater than 4 years post-operatively and the mean was 55 months. Mean current ES was significantly improved from preop (n=100, 1 ± 1 vs 7 ± 2, p 3 and 4 patients required procedural reintervention on the lower esophageal sphincter. Reinterventions were successful in 75% of patients (3/4), with current ES ≤ 3. The rate of objective GERD was 33% (15/45). Esophageal physiology was improved with a decrease in median IRP (11 ± 4 vs 33 ± 15 mmHg, p

BACKGROUND: This study aimed to quantify normative values of phase-specific intrabolus pressure (IBP) and esophageal distensibility using 4D analysis of high-resolution-impedance-manometry (HRIM). METHODS: HRIM studies of supine swallows from 34 normal controls were analyzed with respect to the four phases of bolus transit: 1) accommodation, 2) compartmentalization, 3) peristalsis/esophageal emptying, and 4) ampullary emptying. Phase-specific IBP, bolus volume, and distensibility index (DI) in the esophageal body and esophagogastric junction (EGJ) during phases 1–3 were extracted. RESULTS: The median (5–95(th)/IQR) IBP values were: phase 1: 4.0 (−2.0–10.4/1.9–5.8) mmHg, phase 2: 5.7 (0.2–14.1/3.6–8.9) mmHg, and phase 3: 11.2 (2.9–19.4/7.7–15.1) mmHg. The median bolus volume calculated by integrating impedance planimetry cross-sectional areas was 4.1 ml during the compartmentalization phase. The EGJ-DI at max EGJ diameter during phase 2 and 3 was 2.8 (1.1–9.5/1.8–3.7) mm(2)/mmHg and 6.0 (3.2–20.3/5.1–7.8) mm(2)/mmHg, respectively. The phase 3 EGJ-DI values (6.0 (3.2–20.3/5.1–7.8) mm(2)/mmHg) were similar to those calculated using functional lumen imaging probe (FLIP) at the 60-ml volume on the same subjects (5.8 (3.5–7.2/5.0–6.4) mm(2)/mmHg). CONCLUSIONS & INFERENCES: 4D-HRIM provides a standardized methodology to track the nadir impedance and provide measurements of IBP during maximal distention across phases 1–3 of bolus transit. Median IBP and delta IBP were different across the phases, supporting the need to define IBP by phase. Additionally, the EGJ-DI calculated during phase 3 was similar to the 60-ml EGJ-DI from FLIP in the same subjects suggesting that 4D-HRIM can quantify EGJ opening during primary peristalsis.

A unique motor response to sustained esophageal distension, repetitive antegrade contractions (RACs), is observed using functional luminal imaging probe (FLIP) panometry. However, physiologic mechanisms related to this response are unexplored. This study aimed to evaluate the impact of cholinergic inhibition with atropine on the esophageal contractile response to sustained distention, including RACs, among healthy volunteers.8 asymptomatic volunteers (ages 22-45) were evaluated in a crossover study design with 16-cm FLIP positioned across the esophagogastric junction and distal esophagus during sedated upper endoscopy. The FLIP study involving stepwise volumetric distension was performed twice in each subject, at baseline and again after atropine (15 mcg/kg) was administered intravenously. FLIP panometry was analyzed to assess the contractile response to distension.Antegrade contractions, lumen-occluding contractions, and a RAC pattern were observed in 8/8, 8/8, and 7/8(88%) subjects, respectively, at baseline and in 5/8 (63%), 2/8 (25%) and 2/8 (25%) subjects after atropine. The rate of contractions in the RAC pattern was similar (6-7 contractions per minute) before and after atropine. Compared with the baseline study, distension-induced contractility was triggered at higher fill volumes after atropine. FLIP pressures were lower in response to volumetric filling after atropine than at baseline.The vigor and triggering of the esophageal contractile response to distension is reduced by cholinergic inhibition in asymptomatic controls. The observation that the rate of contractions did not change when patients developed repetitive contractile responses suggests that this rate is not modified by cholinergic inhibition once contractility is triggered.

The functional luminal imaging probe (FLIP) uses high-resolution planimetry to provide a three-dimensional image of the esophageal lumen by measuring diameter, volume, and pressure changes. Literature surrounding use of FLIP has demonstrated its clinical utility as a diagnostic tool and as a device to guide and measure response to therapy. FLIP can assess and guide treatments for esophageal disease states including gastroesophageal reflux disease, achalasia, and eosinophilic esophagitis. FLIP may become the initial test for patients with undifferentiated dysphagia at their index endoscopy. This article summarizes use of FLIP in assessing sphincter function, wall stiffness, and motility to guide treatments.

Background/Aims High-resolution manometry (HRM) performed without sedation is the standard procedure. However, some patients cannot tolerate transnasal placement of the manometry catheter. We aim to assess the practice of performing manometry after endoscopy with conscious sedation by evaluating its impact on esophageal motility findings. Methods Twelve asymptomatic adult volunteers and 7 adult patients completed high-resolution impedance manometry (HRIM) approximately 1 hour after conscious sedation with midazolam and fentanyl (post-sedation) and again on a different day with no-sedation. The no-sedation HRIM involved 2 series of swallows separated in time by 20 minutes (no-sedation-1 and no-sedation-2) for the volunteers; patients completed only 1 series of swallows for no-sedation HRM. Results A motility diagnosis of normal motility was observed in all 12 volunteers post-sedation. Two volunteers had a diagnosis of borderline ineffective esophageal motility, one during the no-sedation-1 period and the other during the no-sedation-2 period; all of the other no-sedation HRIM studies yielded a normal motility diagnosis. Six of seven patients had the same diagnosis in both no-sedation and post-sedation HRM, including 1 distal esophageal spasm, 3 achalasia (2 type II and 1 type III), and 2 esophagogastric junction outflow obstruction. Only one patient’s HRM classification changed from ineffective esophageal motility at no-sedation to normal esophageal motility at post-sedation. Conclusions Performing HRIM after endoscopy with conscious sedation had minimal clinical impact on the motility diagnosis or motility parameters. Thus, this approach may be a viable alternative for patients who cannot tolerate unsedated catheter placement. (J Neurogastroenterol Motil 2020;26:352-361)

Background and Aims Endoluminal functional luminal imaging probe (EndoFLIP) is an imaging tool that measures the physiologic characteristics of GI sphincters. In this study, we used EndoFLIP to evaluate the association between the pyloric physiologic measurements and the clinical outcomes of gastric peroral endoscopic myotomy (G-POEM) in patients with refractory gastroparesis. Methods Thirty-seven patients from 5 centers who underwent G-POEM for management of refractory gastroparesis and had EndoFLIP measurements were evaluated. Cross-sectional area (CSA), balloon pressure, and the distensibility index (DI) of the pylorus were evaluated by EndoFLIP at 40 mL and 50 mL balloon fills before and after G-POEM. One-year clinical success and change in gastric emptying study 3 months after the G-POEM procedure were compared with the EndoFLIP measurements. Results Clinical success was achieved in 26 (70%) patients. Post–G-POEM CSA and DI were significantly higher in the clinical success group with both 40-mL volume distension (CSA: 89.9 ± 64.8 vs 172.5 ± 71.9 mm2, P =.003; DI: 5.8 ± 4.4 vs 8.8 ± 6.1 mm2/mm Hg, P =.043) and 50-mL volume distention (CSA: 140.1 ± 89.9 vs 237.5 ± 80.3 mm2, P =.003; DI: 5.6 ± 3.3 vs 9.9 ± 6.6 mm2/mm Hg, P =.049). CSA using 40-mL volume distention with an area under the curve of 0.83 yielded a specificity of 91% and a sensitivity of 71% at a cutoff point of 154 mm2. Conclusions Post–G-POEM CSA of the pylorus is associated with clinical success and improvement in a gastric emptying scan after G-POEM. EndoFLIP measurements of the pylorus have the potential to be used as a tool to predict the clinical outcome of G-POEM.

IntroductionCompetency-based medical education (CBME) for interpretation of esophageal manometry is lacking; therefore, motility experts and instructional designers developed the esophageal manometry competency (EMC) program: a personalized, adaptive learning program for interpretation of esophageal manometry. The aim of this study was to implement EMC among Gastroenterology (GI) trainees and assess the impact of EMC on competency in manometry interpretation.MethodsGI fellows across 14 fellowship programs were invited to complete EMC from February 2018 to October 2018. EMC includes an introductory video, baseline assessment of manometry interpretation, individualized learning pathways, and final assessment of manometry interpretation. The primary outcome was competency for interpretation in 7 individual skill sets.ResultsForty-four GI trainees completed EMC. Participants completed 30 cases, each including 7 skill sets. At baseline, 4 (9%) participants achieved competency for all 7 skills compared with 24 (55%) at final assessment (P < 0.001). Competency in individual skills increased from a median of 4 skills at baseline to 7 at final assessment (P < 0.001). The greatest increase in skill competency was for diagnosis (Baseline: 11% vs Final: 68%; P < 0.001). Accuracy improved for distinguishing between 5 diagnostic groups and was highest for the Outflow obstructive motility disorder (Baseline: 49% vs Final: 76%; P < 0.001) and Normal motor function (50% vs 80%; P < 0.001).DiscussionThis prospective multicenter implementation study highlights that an adaptive web-based training platform is an effective tool to promote CBME. EMC completion was associated with significant improvement in identifying clinically relevant diagnoses, providing a model for integrating CBME into subspecialized areas of training.

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the "2019 Seoul Consensus on Esophageal Achalasia Guidelines") were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

Patients with gastroesophageal reflux disease (GERD) present with heterogeneous symptoms, response to treatment, and physiologic profiles, requiring distinct and personalized management. This article provides a stepwise framework to phenotype GERD beginning with (1) characterization of symptom profile and response to acid suppression; (2) endoscopic evaluation of mucosal and anatomic integrity; (3) ambulatory reflux monitoring to characterize reflux burden and sensitivity; and (4) esophageal physiologic testing to assess gastroesophageal reflux mechanism and effectors of reflux clearance, and evaluate for alternate causes.

OBJECTIVES Symptoms are inconsistently associated with esophageal motor findings on high-resolution manometry (HRM). We aimed to evaluate predictors of dysphagia severity, including esophageal hypervigilance and visceral anxiety, among patients evaluated with HRM. METHODS Adult patients undergoing HRM at 4 academic medical centers (United States and France) were prospectively evaluated. HRM was completed and analyzed per the Chicago Classification v3.0. Validated symptom scores, including the Brief Esophageal Dysphagia Questionnaire and Esophageal Hypervigilance and Anxiety Scale, were completed at the time of HRM. RESULTS Two hundred thirty-six patients, aged 18-85 (mean 53) years, 65% female, were included. Approximately 59 (25%) patients had a major motor disorder on HRM: 19 achalasia, 24 esophagogastric junction outflow obstruction, 12 absent contractility, and 4 jackhammer. Approximately 177 (75%) patients did not have a major motor disorder: 71 ineffective esophageal motility and 106 normal motility. Having a major motor disorder was a significant predictor of dysphagia severity (Radj = 0.049, P < 0.001), but the Esophageal Hypervigilance and Anxiety Scale score carried a predictive relationship of Brief Esophageal Dysphagia Questionnaire that was 2-fold higher than having a major motor disorder: Radj = 0.118 (P < 0.001). This finding remained when evaluated by the major motor disorder group. HRM metrics were nonsignificant. DISCUSSION In a prospective, international multicenter study, we found that esophageal hypervigilance and visceral anxiety were the strongest predictors of dysphagia severity among patients evaluated with HRM. Thus, an assessment of esophageal hypervigilance and visceral anxiety is important to incorporate when evaluating symptom severity in clinical practice and research studies.

We used in silico models to investigate the impact of the dimensions of myotomy, contraction pattern, the tone of the esophagogastric junction (EGJ), and musculature at the myotomy site on esophageal wall stresses potentially leading to the formation of a blown-out myotomy (BOM). We performed three sets of simulations with an in silico esophagus model, wherein the myotomy-influenced region was modeled as an elliptical section devoid of muscle fibers. These sets investigated the effects of the dimensions of myotomy, differing esophageal contraction types, and differing esophagogastric junction (EGJ) tone and wall stiffness at the myotomy affected region on esophageal wall stresses potentially leading to BOM. Longer myotomy was found to be accompanied by a higher bolus volume accumulated at the myotomy site. With respect to esophageal contractions, deformation at the myotomy site was greatest with propagated peristalsis, followed by combined peristalsis and spasm, and pan-esophageal pressurization. Stronger EGJ tone with respect to the wall stiffness at the myotomy site was found to aid in increasing deformation at the myotomy site. In addition, we found that an esophagus with a shorter myotomy performed better at emptying the bolus than that with a longer myotomy. Shorter myotomies decrease the chance of BOM formation. Propagated peristalsis with EGJ outflow obstruction has the highest chance of BOM formation. We also found that abnormal residual EGJ tone may be a co-factor in the development of BOM, whereas remnant muscle fibers at myotomy site reduce the risk of BOM formation. NEW & NOTEWORTHY Blown-out myotomy (BOM) is a complication observed after myotomy, which is performed to treat achalasia. In silico simulations were performed to identify the factors leading to BOM formation. We found that a short myotomy that is not transmural and has some structural architecture intact reduces the risk of BOM formation. In addition, we found that high esophagogastric junction tone due to fundoplication is found to increase the risk of BOM formation.

Background/PurposePatients with systemic sclerosis (SSc) display a complex clinical phenotype. There are numerous studies that relate transcriptional signatures from PBMC or whole skin of SSc patients to disease activity. However, analyses of whole tissue RNA-sequencing studies are subjected to changes in cellular composition that can drive gene expression signatures and a loss of the ability to detect biologically important transcriptional changes within minority cell populations. Here, we focused on circulating monocytes, which have been shown to exist as two central populations classical (CM) and non-classical (NCM).MethodsSSc patients were recruited from four different sites that form PRESS: Northwestern University, University of Texas, University of Michigan and University of Utah. Comprehensive clinical data was collected for all patients. We isolated CM and NCM from these patients and age, sex, and race-matched healthy volunteers were used as controls. RNA-seq was performed on CM and NCM populations as well as on isolated bulk macrophages from skin.ResultsWe first performed RNA-seq on CM, which are the predominant population in circulation. In order to capture the variability across the SSc cohort, we defined 1790 differentially expressed genes in each patient. We then used these genes to cluster patients into 3 subgroups: Groups A-C. Group A exhibited the strongest interferon signature and innate immune pathways. Group B patients expressed genes in the same pathways but was also enriched for response to cAMP and corticosteroids. Both Group B and Group C exhibited upregulation of genes associated with vasculature development and blood vessel formation. Group C uniquely upregulated TGFB pathways. Next, we performed RNA-seq on NCM isolated from the same patients. When NCM were clustered based on the same 1790 genes as CM, we found that Groups A and C were recapitulated, while Group B was less cohesive. Our analysis stratified SSc patients based on their transcriptional profiles in monocytes but was agnostic to their clinical presentation. We found that Group B and C patients exhibited significantly worsened lung function at the time of monocyte isolation than Group A patients. However, there were no significant differences in skin disease. We then isolated macrophages from skin biopsies of SSc patients and showed that the transcriptional profile of Group A and C in SSc patients was conserved. We also used gene expression data from another study on monocytes which stratified patients based on disease presentation. We found that Group A accurately distinguished dcSSc and ncSSc patients from controls, but not lcSSc.ConclusionWe are the first to show that transcriptomic analysis of classical and non-classical circulating monocytes can unbiasedly stratify SSc patients and correlate with disease activity outcome measures.

BACKGROUND & AIMS: Esophageal hypervigilance and anxiety are emerging as important drivers of dysphagia symptoms and reduced quality of life across esophageal diagnoses. The esophageal hypervigilance and anxiety scale (EHAS) is a validated measure of these cognitive-affective processes. However, its length may preclude it from use in clinical practice. We aimed to create a short form version of the EHAS using established psychometric practices. METHODS: A retrospective review of a registry of patients who visited a university-based esophageal motility clinic for diagnostic testing was conducted. Patients were included if they completed the 15-item EHAS and questionnaires assessing dysphagia severity and health-related quality of life (HRQOL) at the time of motility testing. Principle components factor analysis identified items for possible removal. Tests for reliability and concurrent validity were performed on the full EHAS and short-form version (EHAS-7). RESULTS: 3,976 adult patients with confirmed esophageal disease were included: 30% with achalasia or EGJOO, 13% with EoE, 13% with GERD, 39% normal motility. Eight items were removed from the scale based on a factor loading of > 0.70, resulting in a single scale 7-item EHAS-7 scored from 0 to 28. The EHAS-7 demonstrated excellent internal consistency (α = 0.91) and split-half reliability (0.88) as was found in the full EHAS in the current study and prior validation. Concurrent validity existed between the EHAS-7 and measures of dysphagia (r = 0.33) and HRQOL (r = -0.73, both P < .001). CONCLUSIONS: The EHAS-7 is a 7-item scale to assess esophageal hypervigilance and symptom-specific anxiety that performs as well as the original 15-item version. Shorter questionnaires allow for implementation in clinical practice. The EHAS-7 is a useful tool for clinicians to quickly assess how hypervigilance and anxiety may be contributing to their patients' clinical presentations. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:20 issue:2 pages:E64-E73 ispartof: location:United States status: published

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.

A FLIP device gives cross-sectional area along the length of the esophagus and one pressure measurement, both as a function of time. Deducing mechanical properties of the esophagus including wall material properties, contraction strength, and wall relaxation from these data is a challenging inverse problem. Knowing mechanical properties can change how clinical decisions are made because of its potential for in-vivo mechanistic insights. To obtain such information, we conducted a parametric study to identify peristaltic regimes by using a 1D model of peristaltic flow through an elastic tube closed on both ends and also applied it to interpret clinical data. The results gave insightful information about the effect of tube stiffness, fluid/bolus density and contraction strength on the resulting esophagus shape through quantitive representations of the peristaltic regimes. Our analysis also revealed the mechanics of the opening of the contraction area as a function of bolus flow resistance. Lastly, we concluded that peristaltic driven flow displays three modes of peristaltic geometries, but all physiologically relevant flows fall into two peristaltic regimes characterized by a tight contraction.

This study aimed to develop a diagnostic tool using machine learning to apply functional luminal imaging probe (FLIP) panometry data to determine the probability of esophagogastric junction (EGJ) obstruction as determined using the Chicago Classification version 4.0 (CCv4.0) and high-resolution manometry (HRM).Five hundred and fifty-seven adult patients that completed FLIP and HRM (with a conclusive CCv4.0 assessment of EGJ outflow) and 35 asymptomatic volunteers ("controls") were included. EGJ opening was evaluated with 16-cm FLIP performed during sedated endoscopy via EGJ-distensibility index and maximum EGJ diameter. HRM was classified according to the CCv4.0 as conclusive disorders of EGJ outflow or normal EGJ outflow (timed barium esophagram applied when required and available). The probability tool utilized Bayesian additive regression treesBART, which were evaluated using a leave-one-out approach and a holdout test set.Per HRM and CCv4.0, 243 patients had a conclusive disorder of EGJ outflow while 314 patients (and all 35 controls) had normal EGJ outflow. The model accuracy to predict EGJ obstruction (based on leave-one-out/holdout test set, respectively) was 89%/90%, with 87%/85% sensitivity, 92%/97% specificity, and an area under the receiver operating characteristic curve of 0.95/0.97. A free, open-source tool to calculate probability for EGJ obstruction using FLIP metrics is available at https://www.wklytics.com/nmgi/prob_flip.html.Application of FLIP metrics utilizing a probabilistic approach incorporates the diagnostic confidence (or uncertainty) into the clinical interpretation of EGJ obstruction. This tool can provide clinical decision support during application of FLIP Panometry for evaluation of esophageal motility disorders.

The pathogenesis of esophageal disorders is related to the esophageal wall mechanics. Therefore, to understand the underlying fundamental mechanisms behind various esophageal disorders, it is crucial to map the esophageal wall mechanics-based parameters onto physiological and pathophysiological conditions corresponding to altered bolus transit and supraphysiologic IBP. In this work, we present a hybrid framework that combines fluid mechanics and machine learning to identify the underlying physics of the various esophageal disorders and maps them onto a parameter space which we call the virtual disease landscape (VDL). A one-dimensional inverse model processes the output from an esophageal diagnostic device called endoscopic functional lumen imaging probe (EndoFLIP) to estimate the mechanical "health" of the esophagus by predicting a set of mechanics-based parameters such as esophageal wall stiffness, muscle contraction pattern and active relaxation of esophageal walls. The mechanics-based parameters were then used to train a neural network that consists of a variational autoencoder (VAE) that generates a latent space and a side network that predicts mechanical work metrics for estimating esophagogastric junction motility. The latent vectors along with a set of discrete mechanics-based parameters define the VDL and form clusters corresponding to the various esophageal disorders. The VDL not only distinguishes different disorders but can also be used to predict disease progression in time. Finally, we also demonstrate the clinical applicability of this framework for estimating the effectiveness of a treatment and track patient condition after a treatment., 26 pages, 17 figures

Background This study aimed to build and evaluate a deep learning, artificial intelligence (AI) model to automatically classify swallow types based on raw data from esophageal high-resolution manometry (HRM). Methods HRM studies on patients with no history of esophageal surgery were collected including 1,741 studies with 26,115 swallows labeled by swallow type (normal, hypercontractile, weak-fragmented, failed, and premature) by an expert interpreter per the Chicago Classification. The dataset was stratified and split into train/validation/test datasets for model development. Long short-term memory (LSTM), a type of deep-learning AI model, was trained and evaluated. The overall performance and detailed per-swallow type performance were analyzed. The interpretations of the supine swallows in a single study were further used to generate an overall classification of peristalsis. Key results The LSTM model for swallow type yielded accuracies from the train/validation/test datasets of 0.86/0.81/0.83. The model's interpretation for study-level classification of peristalsis yielded accuracy of 0.88 in the test dataset. Among model misclassification, 535/698 (77%) swallows and 25/35 (71%) studies were to adjacent categories, for example, normal to weak or normal to ineffective, respectively. Conclusions and inferences A deep-learning AI model can automatically and accurately identify the Chicago Classification swallow types and peristalsis classification from raw HRM data. While future work to refine this model and incorporate overall manometric diagnoses are needed, this study demonstrates the role that AI will serve in the interpretation and classification of esophageal HRM studies.

Esophageal disorders are related to the mechanical properties and function of the esophageal wall. Therefore, to understand the underlying fundamental mechanisms behind various esophageal disorders, it is crucial to map mechanical behavior of the esophageal wall in terms of mechanics-based parameters corresponding to altered bolus transit and increased intrabolus pressure. We present a hybrid framework that combines fluid mechanics and machine learning to identify the underlying physics of various esophageal disorders (motility disorders, eosinophilic esophagitis, reflux disease, scleroderma esophagus) and maps them onto a parameter space which we call the virtual disease landscape (VDL). A one-dimensional inverse model processes the output from an esophageal diagnostic device called the functional lumen imaging probe (FLIP) to estimate the mechanical "health" of the esophagus by predicting a set of mechanics-based parameters such as esophageal wall stiffness, muscle contraction pattern and active relaxation of esophageal wall. The mechanics-based parameters were then used to train a neural network that consists of a variational autoencoder that generated a latent space and a side network that predicted mechanical work metrics for estimating esophagogastric junction motility. The latent vectors along with a set of discrete mechanics-based parameters define the VDL and formed clusters corresponding to specific esophageal disorders. The VDL not only distinguishes among disorders but also displayed disease progression over time. Finally, we demonstrated the clinical applicability of this framework for estimating the effectiveness of a treatment and tracking patients' condition after a treatment.