Comparative Genomic Analysis of Bacterial Data in BV-BRC: An Example Exploring Antimicrobial Resistance.

As genomic and related data continue to expand, research biologists are often hampered by the computational hurdles required to analyze their data. The National Institute of Allergy and Infectious Diseases (NIAID) established the Bioinformatics Resource Centers (BRC) to assist researchers with their analysis of genome sequence and other omics-related data. Recently, the PAThosystems Resource Integration Center (PATRIC), the Influenza Research Database (IRD), and the Virus Pathogen Database and Analysis Resource (ViPR) BRCs merged to form the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) at https://www.bv-brc.org/ . The combined BV-BRC leverages the functionality of the original resources for bacterial and viral research communities with a unified data model, enhanced web-based visualization and analysis tools, and bioinformatics services. Here we demonstrate how antimicrobial resistance data can be analyzed in the new resource.

Gastric per-oral endoscopic myotomy (G-POEM) for refractory gastroparesis: results from an international prospective trial.

OBJECTIVE: Although gastric per-oral endoscopic myotomy (G-POEM) is considered a promising technique for the management of refractory gastroparesis, high-quality evidence is limited. We prospectively investigated the efficacy and safety of G-POEM in unselected patients with refractory gastroparesis. DESIGN: In five tertiary centres, patients with symptomatic gastroparesis refractory to standard medical therapy and confirmed by impaired gastric emptying were included. The primary endpoint was clinical success, defined as at least one score decrease in Gastroparesis Cardinal Symptom Index (GCSI) with ≥25% decrease in two subscales, at 12 months. GCSI Score and subscales, adverse events (AEs) and 36-Item Short Form questionnaire of quality of life were evaluated at baseline and 1, 3, 6 and 12 months after G-POEM. Gastric emptying study was performed before and 3 months after the procedure. RESULTS: Of 80 enrolled patients, 75 patients (94%) completed 12-month follow-up. Clinical success at 12 months was 56% (95% CI, 44.8 to 66.7). GCSI Score (including subscales) improved moderately after G-POEM (p<0.05). In a regression model, a baseline GCSI Score >2.6 (OR=3.23, p=0.04) and baseline gastric retention >20% at 4 hours (OR=3.65, p=0.03) were independent predictors of clinical success at 12 months, as was early response to G-POEM at 1 month after therapy (OR 8.75, p<0.001). Mild procedure-related AEs occurred in 5 (6%) patients. CONCLUSION: G-POEM is a safe procedure, but showed only modest overall effectiveness in the treatment of refractory gastroparesis. Further studies are required to identify the best candidates for G-POEM; unselective use of this procedure should be discouraged. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry NCT02732821.

Surveillance Cessation for Barrett's Esophagus: A Survey of Gastroenterologists.

INTRODUCTION: Regular endoscopic surveillance is the gold standard Barrett's esophagus (BE) surveillance, yet harms of surveillance for some patients may outweigh the benefits. We sought to characterize physicians' BE surveillance cessation recommendations. METHODS: We surveyed gastroenterologists about their BE surveillance recommendations varying patient age, comorbidity, and BE length. RESULTS: Clinicians varied in recommendations for repeat surveillance. Patient age showed the largest variation among decisions, whereas BE length varied the least. DISCUSSION: Age and comorbidities seem to influence BE surveillance cessation decisions, but with variation. Clear cessation guidelines balancing the risks and benefits for BE surveillance are warranted.

Retrospective multicenter study on endoscopic treatment of upper GI postsurgical leaks.

BACKGROUND AND AIMS: Therapeutic endoscopy plays a critical role in the management of upper GI (UGI) postsurgical leaks. Data are scarce regarding clinical success and safety. Our aim was to evaluate the effectiveness of endoscopic therapy for UGI postsurgical leaks and associated adverse events (AEs) and to identify factors associated with successful endoscopic therapy and AE occurrence. METHODS: This was a retrospective, multicenter, international study of all patients who underwent endoscopic therapy for UGI postsurgical leaks between 2014 and 2019. RESULTS: Two hundred six patients were included. Index surgery most often performed was sleeve gastrectomy (39.3%), followed by gastrectomy (23.8%) and esophagectomy (22.8%). The median time between index surgery and commencement of endoscopic therapy was 16 days. Endoscopic closure was achieved in 80.1% of patients after a median follow-up of 52 days (interquartile range, 33-81.3). Seven hundred seventy-five therapeutic endoscopies were performed. Multimodal therapy was needed in 40.8% of patients. The cumulative success of leak resolution reached a plateau between the third and fourth techniques (approximately 70%-80%); this was achieved after 125 days of endoscopic therapy. Smaller leak initial diameters, hospitalization in a general ward, hemodynamic stability, absence of respiratory failure, previous gastrectomy, fewer numbers of therapeutic endoscopies performed, shorter length of stay, and shorter times to leak closure were associated with better outcomes. Overall, 102 endoscopic therapy-related AEs occurred in 81 patients (39.3%), with most managed conservatively or endoscopically. Leak-related mortality rate was 12.4%. CONCLUSIONS: Multimodal therapeutic endoscopy, despite being time-consuming and requiring multiple procedures, allows leak closure in a significant proportion of patients with a low rate of severe AEs.

Impact of gastric per-oral endoscopic myotomy on static and dynamic pyloric function in gastroparesis patients.

BACKGROUND: Functional Lumen Imaging Probe (EndoFLIP) tests typically measure static pyloric parameters, but the pylorus exhibits phasic variations on manometry. Dynamic changes in pyloric function have not been quantified using EndoFLIP, and the impact of Gastric Per-Oral Endoscopic Myotomy (G-POEM) on static and dynamic pyloric activity in gastroparesis is unknown. METHODS: EndoFLIP balloon inflation to 30, 40, and 50 mL was performed to measure mean, maximum, and minimum values and variability in pyloric diameter and distensibility before and after G-POEM in 20 patients with refractory gastroparesis. The impact of phasic contractions on these pyloric measures was compared. KEY RESULTS: G-POEM increased mean (P < .0001) and maximum (P = .0002) pyloric diameters and mean (P = .02) and maximum (P = .02) pyloric distensibility on 50 mL EndoFLIP inflation but not intraballoon pressures or minimum diameters or distensibility. Temporal variability of pyloric diameter (P = .02) and distensibility (P = .02) also increased after G-POEM. Phasic coupled contractions propagating from the antrum through the pylorus were observed in 37.5% of recordings; other phasic activity including isolated pyloric contractions were seen in 23.3%. Variability of pyloric diameter and distensibility tended to be higher during recordings with phasic activity. Some pyloric responses to G-POEM were influenced by age, gastroparesis etiology, gastric emptying, and prior botulinum toxin injection. CONCLUSIONS & INFERENCES: Pyloric activity exhibits dynamic changes on EndoFLIP testing in gastroparesis. G-POEM increases maximal but not minimal diameter and distensibility with increased variations, suggesting this therapy enhances pyloric opening but may not impair pyloric closure. Phasic pyloric contractions contribute to variations in pyloric activity.

Role of endoscopic functional luminal imaging probe in predicting the outcome of gastric peroral endoscopic pyloromyotomy (with video).

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.

CD4+ Tissue-resident Memory T Cells Expand and Are a Major Source of Mucosal Tumour Necrosis Factor α in Active Crohn's Disease.

BACKGROUND AND AIMS: Tumour necrosis factor [TNF]α- and IL-17A-producing T cells are implicated in Crohn's disease [CD]. Tissue-resident memory T [TRM] cells are tissue-restricted T cells that are regulated by PR zinc finger domain 1 [PRDM1], which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defence but their role in CD is unknown. We thus examined CD4+ TRM cells in CD. METHODS: Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterise CD4+ TRM cells. RESULTS: CD4+ TRM cells are the most abundant memory T cell population and are the major T cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD which are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells. CONCLUSIONS: CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting that they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.