A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus.

Background & Aims: Functional lumen imaging probe (FLIP) panometry provides assessment of the esophagogastric junction opening and esophageal body contractile activity during an endoscopic procedure and is increasingly being incorporated into comprehensive esophageal motility assessments. The aim of this study was to provide a standardized approach and vocabulary to the procedure and interpretation and update the motility classification scheme.

Methods: A working group of 19 FLIP panometry experts convened in a modified Delphi consensus process to produce and assess statements on the FLIP panometry procedure and interpretation.

Real-World Effectiveness and Use of Dupilumab in Eosinophilic Esophagitis.

Introduction: Dupilumab, the first US Food and Drug Administration-approved treatment for eosinophilic esophagitis (EoE), lacks real-world data on use and effectiveness.

Methods: We conducted a retrospective cohort study of 70 patients with EoE prescribed dupilumab, comparing prescriber type, indication, follow-up, and response.

Results: Indications varied with gastroenterologists commonly prescribing for treatment-refractory cases and allergists as first-line therapy.

AGA Clinical Practice Update on the Diagnosis and Management of Extraesophageal Gastroesophageal Reflux Disease: Expert Review.

Description: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert advice regarding the clinical management of patients with suspected extraesophageal gastroesophageal reflux disease.

Methods: This article provides practical advice based on the available published evidence including that identified from recently published reviews from leading investigators in the field, prospective and population studies, clinical trials, and recent clinical guidelines and technical reviews. This best practice document is not based on a formal systematic review.

Interrater Reliability of Functional Lumen Imaging Probe Panometry and High-Resolution Manometry for the Assessment of Esophageal Motility Disorders.

Introduction: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations.

Methods: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies.

Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management.

Nearly all patients with systemic sclerosis (SSc) are negatively affected by dysfunction in the gastrointestinal tract, and the severity of gastrointestinal disease in SSc correlates with high mortality. The clinical complications of this dysfunction are heterogeneous and include gastro-oesophageal reflux disease, gastroparesis, small intestinal bacterial overgrowth, intestinal pseudo-obstruction, malabsorption and the requirement for total parenteral nutrition. The abnormal gastrointestinal physiology that promotes the clinical manifestations of SSc gastrointestinal disease throughout the gastrointestinal tract are diverse and present a range of therapeutic targets.

Clinical role of ambulatory reflux monitoring in PPI non-responders: recommendation statements.

Background: Optimal ambulatory reflux monitoring methodology in symptomatic reflux patients continues to be debated.

Aims: 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.

Variability in endoscopic assessment of Nissen fundoplication wrap integrity and hiatus herniation.

Background: Upper endoscopy (EGD) is frequently performed in patients with esophageal complaints following anti-reflux surgery such as fundoplication. Endoscopic evaluation of fundoplication wrap integrity can be challenging. Our primary aim in this pilot study was to evaluate the accuracy and confidence of assessing Nissen fundoplication integrity and hiatus herniation among gastroenterology (GI) fellows, subspecialists, and foregut surgeons.

Zotatifin, an eIF4A-Selective Inhibitor, Blocks Tumor Growth in Receptor Tyrosine Kinase Driven Tumors.

Oncoprotein expression is controlled at the level of mRNA translation and is regulated by the eukaryotic translation initiation factor 4F (eIF4F) complex. eIF4A, a component of eIF4F, catalyzes the unwinding of secondary structure in the 5'-untranslated region (5'-UTR) of mRNA to facilitate ribosome scanning and translation initiation. Zotatifin (eFT226) is a selective eIF4A inhibitor that increases the affinity between eIF4A and specific polypurine sequence motifs and has been reported to inhibit translation of driver oncogenes in models of lymphoma.

Classifying Esophageal Motility by FLIP Panometry: A Study of 722 Subjects With Manometry.

Introduction: 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.

Phenotyping patients with borderline elevated esophageal acid exposure.

Acid exposure time (AET) <4% on ambulatory reflux monitoring definitively rules out pathologic gastroesophageal acid reflux, while AET >6% indicates pathologic reflux per the Lyon Consensus, leaving AET of 4-6% as borderline. We aimed to elucidate the borderline AET population and identify metrics that could help differentiate this group. A total of 50 subjects in each group, AET <4, 4-6, and >6% on pH-impedance monitoring between 2015 and 2019, were retrospectively reviewed.

Perspectives on electronic portal use among patients treated with medications for opioid use disorder in primary care.

Objectives: Office-based opioid treatment (OBOT) with buprenorphine is increasingly integrated in primary care to treat opioid use disorder (OUD). Online portals seek to engage patients in care of their chronic medical conditions, yet we know little about how patients with OUD experience these portals. Our study explores how patients with OUD perceive the impact of portal use on addiction treatment and clinical care.

Chicago Classification Update (v4.0): Technical review on diagnostic criteria for hypercontractile esophagus.

Hypercontractile esophagus (HE), defined by the Chicago Classification version 3.0 (CCv3.0) as 20% or more hypercontractile peristalsis (Distal Contractile Integral >8000 mmHg·s·cm) on high-resolution manometry (HRM), is a heterogeneous disorder with variable clinical presentations and natural course, leading to management challenges.

Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A.

The PI3K/AKT/mTOR pathway is often activated in lymphoma through alterations in PI3K, PTEN, and B-cell receptor signaling, leading to dysregulation of eIF4A (through its regulators, eIF4B, eIF4G, and PDCD4) and the eIF4F complex. Activation of eIF4F has a direct role in tumorigenesis due to increased synthesis of oncogenes that are dependent on enhanced eIF4A RNA helicase activity for translation. eFT226, which inhibits translation of specific mRNAs by promoting eIF4A1 binding to 5'-untranslated regions (UTR) containing polypurine and/or G-quadruplex recognition motifs, shows potent antiproliferative activity and significant efficacy against a panel of diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma models with ≤1 mg/kg/week intravenous administration.

Incomplete Response of Gastroesophageal Reflux Symptoms Poorly Predicts Erosive Esophagitis or Barrett's Esophagus.

Background & Aims: Many patients with symptoms of gastroesophageal reflux disease (GERD) not responding to a proton pump inhibitor (PPI) undergo an upper endoscopy. We hypothesized that an incomplete response to a PPI is not associated with findings of esophageal pathology on endoscopy, and that psychological distress is associated inversely with pathology.

Methods: We enrolled consecutive individuals aged 40 to 79 years with prior heartburn or regurgitation.

Management of Eosinophilic Esophagitis: Dietary and Nondietary Approaches.

Eosinophilic esophagitis (EoE) is an allergen-driven chronic inflammatory condition, characterized by symptoms related to esophageal dysfunction and confirmed histologically by esophageal mucosal eosinophilia. Since its first description in the 1990s, the incidence and prevalence of EoE have been on the rise. It is known to affect all ages of various ethnic backgrounds and both sexes; however, it is most seen in White males.

ACG Clinical Guidelines: Clinical Use of Esophageal Physiologic Testing.

Esophageal symptoms are common and may indicate the presence of gastroesophageal reflux disease (GERD), structural processes, motor dysfunction, behavioral conditions, or functional disorders. Esophageal physiologic tests are often performed when initial endoscopic evaluation is unrevealing, especially when symptoms persist despite empiric management. Commonly used esophageal physiologic tests include esophageal manometry, ambulatory reflux monitoring, and barium esophagram.

Per-oral Endoscopic Myotomy Biopsies of Achalasia Patients Reveal Schwann Cell Depletion in the Muscularis Propria.

Achalasia is a neurodegenerative condition resulting in abnormal lower esophageal sphincter relaxation and impaired upstream esophageal body peristalsis. The pathophysiology and natural history of achalasia remain unclear, and evaluation of the histopathogenesis of achalasia has traditionally been challenging because the esophageal wall muscularis propria is not typically accessible via routine endoscopic biopsies.

Clinical impact of routine esophagram after peroral endoscopic myotomy.

Background And Aims: It is unclear whether the common practice of postoperative day (POD) 1 esophagram impacts clinical care or reliably identifies significant adverse events (AEs) related to peroral endoscopic myotomy (POEM). Therefore, we aimed to correlate the most clinically relevant esophagram findings with postoperative outcomes after POEM.

Methods: Patients were retrospectively reviewed and included if they underwent POEM at 1 of the 3 study institutions between 2014 and 2018.

Provider Variability in the Management Patterns of Increased Nonacid Reflux.

Introduction: Increased nonacid reflux is diagnosed in a subgroup of patients with gastroesophageal reflux disease who often present with reflux symptoms refractory to proton-pump inhibitor therapy. Despite the prevalence of this condition, the management approach for patients with increased nonacid reflux can often be varied and unclear.

Aims: Our primary aim was to investigate physician management patterns for patients who had received a diagnosis of increased nonacid reflux on impedance-pH studies.

A Predictor of Pathological Complete Response to Neoadjuvant Chemotherapy Stratifies Triple Negative Breast Cancer Patients with High Risk of Recurrence.

We developed a test to predict which patients will achieve pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) and which will have residual disease (RD). Gene expression data from pretreatment biopsies of patients with all breast cancer subtypes were combined into a 519-patient cohort containing 177 TNBC patients. Two RNA classifiers of 16 genes each were sequentially applied to the total cohort, classifying patients into 3 distinct classes.