Quantified Metrics of Gastric Emptying Delay by Glucagon-Like Peptide-1 Agonists: A Systematic Review and Meta-Analysis With Insights for Periprocedural Management.

INTRODUCTION: Divergent recommendations for periprocedural management of glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks. METHODS: A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as a weighted mean difference with 95% confidence intervals (CIs). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short-acting vs long-acting mechanism of action, and duration of treatment on gastric emptying. RESULTS: Fifteen studies met the inclusion criteria. Five studies (n = 247) utilized gastric emptying scintigraphy. Mean T 1/2 was 138.4 minutes (95% CI 74.5-202.3) for GLP-1 RA vs 95.0 minutes (95% CI 54.9-135.0) for placebo, with a pooled mean difference of 36.0 minutes (95% CI 17.0-55.0, P < 0.01, I2 = 79.4%). Ten studies (n = 411) utilized the acetaminophen absorption test, with no significant delay in gastric emptying measured by T max , area under the curve (AUC) 4hr , and AUC 5hr with GLP-1 RA ( P > 0.05). On meta-regression, the type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying ( P > 0.05). DISCUSSION: While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (acetaminophen absorption test), particularly at time points relevant to periprocedural care.

Efficacy and Safety of Gastric Per-Oral Endoscopic Myotomy (G-POEM): A Systematic Review and Meta-Analysis.

BACKGROUND: Gastric per-oral endoscopic myotomy (G-POEM) is an innovative treatment that has become increasingly utilized for patients with refractory gastroparesis. The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness of G-POEM for the treatment of gastroparesis. METHODS: Individualized search strategies were developed through February 2021 in accordance with the PRISMA and MOOSE guidelines. This meta-analysis was performed by calculating pooled proportions and mean difference preprocedure and postprocedure with rates estimated using random effects models. Measured outcomes included technical success, clinical success, improvement in gastroparesis cardinal symptom index (GCSI), change in gastric emptying rate, alterations in impedance planimetry (functional lumen imaging probe [FLIP]) assessment, and adverse events. RESULTS: A total of 20 studies (n=797 patients; 67.41% female) were included. The mean age was 48.92±11.61 y, with an average duration of 4.24±1.11 y since gastroparesis diagnosis. Technical success was 98.47% [(95% CI: 97.14, 99.19);I2=0.00] with a mean myotomy length of 3.78±1.16 cm. In terms of clinical success, mean preprocedure GCSI scores were 3.38±0.37 and improved significantly postprocedure [weighted mean difference -1.56 (95% CI: -1.89 to -1.24); I2=82.53; P<0.001]. Gastric retention after 4 hours demonstrated ~50% improvement (preprocedure 43.08±9.24% versus postprocedure 22.97±10.19%; P<0.001). FLIP assessment with 40 mL and 50 mL balloons demonstrated a significant increase in diameter, distensibility index, and cross-sectional area postprocedure (all P<0.05). Procedure-associated adverse events occurred among 10.92% [(95% CI 5.09 to 19.32); I2=82.85] of patients. CONCLUSION: G-POEM appears safe and highly effective for the treatment of patients with refractory gastroparesis regardless of symptom predominance or etiology.

Rescue of codon-pair deoptimized respiratory syncytial virus by the emergence of genomes with very large internal deletions that complemented replication.

Recoding viral genomes by introducing numerous synonymous but suboptimal codon pairs-called codon-pair deoptimization (CPD)-provides new types of live-attenuated vaccine candidates. The large number of nucleotide changes resulting from CPD should provide genetic stability to the attenuating phenotype, but this has not been rigorously tested. Human respiratory syncytial virus in which the G and F surface glycoprotein ORFs were CPD (called Min B) was temperature-sensitive and highly restricted in vitro. When subjected to selective pressure by serial passage at increasing temperatures, Min B substantially regained expression of F and replication fitness. Whole-genome deep sequencing showed many point mutations scattered across the genome, including one combination of six linked point mutations. However, their reintroduction into Min B provided minimal rescue. Further analysis revealed viral genomes bearing very large internal deletions (LD genomes) that accumulated after only a few passages. The deletions relocated the CPD F gene to the first or second promoter-proximal gene position. LD genomes amplified de novo in Min B-infected cells were encapsidated, expressed high levels of F, and complemented Min B replication in trans This study provides insight on a variation of the adaptability of a debilitated negative-strand RNA virus, namely the generation of defective minihelper viruses to overcome its restriction. This is in contrast to the common "defective interfering particles" that interfere with the replication of the virus from which they originated. To our knowledge, defective genomes that promote rather than inhibit replication have not been reported before in RNA viruses.

Artificial intelligence in medical imaging for cholangiocarcinoma diagnosis: A systematic review with scientometric analysis.

INTRODUCTION: Artificial intelligence (AI), by means of computer vision in machine learning, is a promising tool for cholangiocarcinoma (CCA) diagnosis. The aim of this study was to provide a comprehensive overview of AI in medical imaging for CCA diagnosis. METHODS: A systematic review with scientometric analysis was conducted to analyze and visualize the state-of-the-art of medical imaging to diagnosis CCA. RESULTS: Fifty relevant articles, published by 232 authors and affiliated with 68 organizations and 10 countries, were reviewed in depth. The country with the highest number of publications was China, followed by the United States. Collaboration was noted for 51 (22.0%) of the 232 authors forming five clusters. Deep learning algorithms with convolutional neural networks (CNN) were the most frequently used classifiers. The highest performance metrics were observed with CNN-cholangioscopy for diagnosis of extrahepatic CCA (accuracy 94.9%; sensitivity 94.7%; and specificity 92.1%). However, some of the values for CNN in CT imaging for diagnosis of intrahepatic CCA were low (AUC 0.72 and sensitivity 44%). CONCLUSION: Our results suggest that there is increasing evidence to support the role of AI in the diagnosis of CCA. CNN-based computer vision of cholangioscopy images appears to be the most promising modality for extrahepatic CCA diagnosis. Our social network analysis highlighted an Asian and American predominance in the research relational network of AI in CCA diagnosis. This discrepancy presents an opportunity for coordination and increased collaboration, especially with institutions located in high CCA burdened countries.

Homemade endoscopic vacuum therapy device for the management of transmural gastrointestinal defects.

OBJECTIVES: Endoscopic vacuum therapy (EVT) possesses a unique mechanism of action providing a less invasive alternative for the management of transmural gastrointestinal defects (TGID). This study evaluates the efficacy and safety of a novel homemade EVT (H-EVT) for the treatment of TGID. METHODS: Retrospective multicenter study including patients who underwent H-EVT for TGID between January 2019 and January 2022. Main outcomes included technical and clinical success as well as safety outcomes. Subgroup analyses were included by defect location and classification. Logistic regression analyses were performed to determine predictors for successful closure. RESULTS: A total of 144 patients were included. Technical success was achieved in all patients, with clinical success achieved in 88.89% after a mean of 3.49 H-EVT exchanges over an average of 23.51 days. After excluding 10 cases wherein it was not possible to achieve negative pressure, successful closure occurred in 95.52% of patients. Time to clinical success was less for defects caused by endoscopic (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.33-1.20) compared to surgical procedures and for patients with simultaneous intracavitary and intraluminal H-EVT placement (HR 0.70; 95% CI 0.55-0.91). Location and classification of defect did not impact clinical success rate. Simultaneous placement of both an intraluminal and intracavitary H-EVT (odds ratio 3.08; 95% CI 1.19-7.95) was a significant predictor of clinical success. Three device-related adverse events (2.08%) occurred. CONCLUSIONS: The use of the H-EVT is feasible, safe, and effective for the management of TGID.

Effect of Endoscopic Bariatric and Metabolic Therapies on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Weight loss via lifestyle intervention remains the mainstay of treatment for nonalcoholic fatty liver disease (NAFLD). Endoscopic bariatric and metabolic therapies (EBMTs) have recently been developed as an alternative treatment option for obesity. This study aimed to assess the effect of FDA-approved EBMTs on NAFLD. METHODS: We searched MEDLINE, EMBASE, Web of Science and Cochrane Central through December 2020 for studies that assessed changes in liver outcomes following EBMT. Primary Outcomes: Liver fibrosis. SECONDARY OUTCOMES: Liver biochemistry, steatosis, NAFLD histological changes and insulin sensitivity. The Grading of Recommendations, Assessment, Development, and Evidence (GRADE) approach was conducted to assess quality of evidence. RESULTS: Of 4994 potential studies, 18 studies with 863 patients were included. Average weight loss was 14.5% of initial weight at a 6-month follow-up. Primary outcomes: Following EBMT, liver fibrosis significantly reduced by standardized mean difference (SMD) of 0.7 (95% CI, 0.1, 1.3; P = .02). SECONDARY OUTCOMES: There were significant improvements in other NAFLD surrogates including alanine aminotransferase (-9.0 U/L; 95% CI, -11.6, -6.4; P < .0001), hepatic steatosis (SMD: -1.0; 95% CI, -1.2, -0.8; P < .0001) and histologic NAFLD activity score (-2.50; 95% CI, -3.5, -1.5; P < .0001). Other metabolic parameters including insulin resistance and waist circumference also significantly improved. The overall quality of the evidence for primary outcomes was low to very low. CONCLUSIONS: EBMTs appear effective at treating NAFLD with significant improvement in liver fibrosis. Given the worsening NAFLD pandemic and limitations of currently available therapies, EBMTs should be further investigated as a potential treatment option for this patient population.

Endoscopic full-thickness resection of colorectal lesions: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) is a novel endoscopic technique for the resection of GI lesions not amenable to standard endoscopic therapy. The primary aim of this study was to perform a systematic review and meta-analysis to evaluate EFTR for the resection of colorectal lesions. METHODS: Individualized searches were developed through October 2020 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Random-effects models were used to determine pooled technical success, margin-negative (R0) resection, adverse events, procedure duration, and rate of recurrence at follow-up. Subgroup analysis was used to assess the impact of specific procedure techniques and regression analyses to determine influence of lesion size. Heterogeneity was assessed with I2 statistics and publication bias by funnel plots using Egger and Begg tests. RESULTS: Fourteen studies (1936 subjects; 39.6% women) were included. Most EFTR lesions were located in the colon (75.8%) with the remaining in the rectum. Mean procedure duration was 45.4 ± 11.4 minutes. Pooled technical success was 87.6% (95% confidence interval [CI], 85.1-89.8; I2 = 33), R0 resection rate was 78.8% (95% CI, 75.7-81.5; I2 = 33), procedure-associated adverse events occurred in 12.2% (95% CI, 9.3-15.9; I2 = 61), and recurrence rate was 12.6% (95% CI, 11.1-14.4; I2 = 0) over an average weighted follow-up of 20.1 ± 3.8 weeks. Regression analyses revealed significantly lower R0 resection (odds ratio, .3; 95% CI, .2-.6; I2 = 61; P = .0003) and higher overall procedure-associated adverse event rates (odds ratio, 3.5; 95% CI, 1.8-7.2; I2 = 55; P = .0004) for lesions >20 mm. CONCLUSIONS: EFTR overall appears to be an effective modality with high technical success and R0 resection rate with a relatively low risk of adverse events and recurrence, with greatest success when lesions are <20 mm.

Needle-based Confocal Laser Endomicroscopy (nCLE) for Evaluation of Pancreatic Cystic Lesions: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Given the variable diagnostic yield of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions (PCLs), novel imaging techniques including needle-based confocal laser endomicroscopy (nCLE) have been devised. The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic performance and safety of nCLE for the diagnosis of PCLs. METHODS: Individualized search strategies were developed in accordance with PRISMA and MOOSE guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. Measured outcomes included diagnostic characteristics and procedure-associated adverse events. A bivariate model was used to compute combined weighted sensitivity, specificity, positive/negative likelihood ratio (LR), diagnostic odds ratio, and summary receiver operating characteristic curve with corresponding 95% confidence intervals (CIs). RESULTS: Seven studies (n=324; mean age: 63.99±5.36 y; 52.47% female) were included. The pooled sensitivity, specificity, positive LR, and negative LR of nCLE was 85% (95% CI, 71-93; I2=74.20%), 99% (95% CI, 90-100; I2=72.60%), 78.66 (95% CI, 7.99-774.68; I2=26.86%), and 0.15 (95% CI, 0.07-0.31; I2=75.84%), respectively. Diagnostic accuracy as measured by summary receiver operating characteristic curve was 99% (95% CI, 98-100). The pooled diagnostic odds ratio was 534 (95% CI, 50-5664; I2=58.00%). Postprocedure pancreatitis developed in 1% (95% CI, 0-3; I2=5.64%) of cases. CONCLUSIONS: On the basis of this meta-analysis, nCLE appears to be an effective and safe technique for the diagnostic evaluation of PCLs. Although moderate-to-high amounts of heterogeneity were present, our results demonstrated that nCLE has a diagnostic accuracy of 99% with a low rate of adverse events.

Trends and Socioeconomic Health Outcomes of Cannabis Use Among Patients With Gastroparesis: A United States Nationwide Inpatient Sample Analysis.

BACKGROUND: Although cannabis may worsen nausea and vomiting for patients with gastroparesis, it may also be an effective treatment for gastroparesis-related abdominal pain. Given conflicting data and a lack of current epidemiological evidence, we aimed to investigate the association of cannabis use on relevant clinical outcomes among hospitalized patients with gastroparesis. MATERIALS AND METHODS: Patients with a diagnosis of gastroparesis were reviewed from the National Inpatient Sample (NIS) database between 2008 and 2014. Gastroparesis was identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes with patients classified based on a diagnosis of cannabis use disorder. Demographics, comorbidities, socioeconomic status, and outcomes were compared between cohorts using χ2 and analysis of variance. Logistic regression was then performed and annual trends also evaluated. RESULTS: A total of 1,473,363 patients with gastroparesis were analyzed [n=33,085 (2.25%) of patients with concomitant cannabis use disorder]. Patients with gastroparesis and cannabis use disorder were more likely to be younger and male gender compared with nonusers (36.7±18.8 vs. 51.9±16.8; P<0.001 and 52.9% vs. 33.5%; P<0.001, respectively). Race/ethnicity was different between groups (P<0.001). Cannabis users had a lower median household income and were more likely to have Medicaid payor status (all P<0.001). Controlling for confounders, length of stay, and mortality were significantly decreased for patients with gastroparesis and cannabis use (all P<0.001). CONCLUSION: While patients with gastroparesis and cannabis use disorder were younger, with a lower socioeconomic status, and disproportionately affected by psychiatric diagnoses, these patients had better hospitalization outcomes, including decreased length of stay and improved in-hospital mortality.

Revision Bariatric Procedures and Management of Complications from Bariatric Surgery.

Bariatric surgery is effective, but may be associated with adverse events. A multi-disciplinary approach including endoscopic interventions can be effective to manage these. Endoscopists should familiarize themselves with gastrointestinal pathology which can occur after bariatric surgery, including nutritional deficiencies, acid reflux, anastomotic stenosis, gallstone disease, leaks, fistulas, and weight regain. Endoscopic interventions including anastomotic stricture dilation, control of bleeding, endoscopic ultrasound-guided approach for endoscopic retrograde cholangiopancreatography, leak or fistula closure via endoscopic suturing or stent placement, and transoral outlet reduction (TORe) or revision obesity surgery endoluminal (ROSE) to address weight regain are among the endoscopic tools which have demonstrated safety and efficacy in the management of adverse events after bariatric surgery.

Lumen Apposition: A Changing Landscape in Therapeutic Endoscopy.

The concept of endoscopic lumen apposition has seen a dramatic shift in the last several decades. Early natural orifice trans-luminal endoscopic surgery (NOTES) concepts have transformed into specialized lumen-apposing metal stents (LAMSs) and delivery devices, which provide endoscopists a minimally invasive alternative to surgical intervention. These LAMSs have become the bedrock of therapeutic endoscopy and provide treatment for a wide spectrum of gastrointestinal disorders. In this review, we summarize the changing landscape of therapeutic endoscopy by highlighting the use of LAMS and future directions as well as alternative devices to achieve lumen apposition.

Endoscopic revision of gastrojejunal anastomosis for the treatment of dumping syndrome in patients with Roux-en-Y gastric bypass: a systematic review and meta-analysis.

BACKGROUND: Dumping syndrome is a known complication of Roux-en-Y gastric bypass (RYGB). Recently, endoscopic gastrojejunal anastomosis (GJA) revision has been employed as a treatment option. The primary aim of this study was to perform a systematic review and meta-analysis for the role of endoscopic GJA revision in patients with RYGB for the treatment of dumping syndrome. METHODS: Search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception through December 2020 in accordance with PRISMA and MOOSE guidelines. Pooled proportions with rates estimated using random effects models were used. Outcomes included pooled technical success, clinical success, adverse events, and rate of reintervention. Heterogeneity was assessed with I2 statistics and publication bias by funnel plot using Egger and Begg tests. RESULTS: Six studies (n = 263 patients; 60.25% female) were included (1 prospective and 5 retrospective). Mean age was 46.27 ± 2.54 years. Average patient weight was 95.59 ± 4.78 kg, BMI of 41.43 ± 3.07 kg/m2, and pre-procedure GJA size of 32.23 ± 8.68 mm. Pooled technical and clinical success was 98.15% and 89.5%. Among studies reporting Sigstad scores, endoscopic GJA revision resulted in a significant improvement [mean Sigstad score difference of - 9.96 (95% CI, - 19.951 to - 0.975); P < 0.03]. Mean procedure time was 37.12 ± 10.40 min with an intra-procedural adverse event rate of 2.42%. Over a mean follow-up of 8.03 ± 6.87 months, post-procedure adverse events occurred in 2.96% of patients with a reintervention rate of 11.54%. CONCLUSION: This systematic review and meta-analysis suggests that endoscopic GJA revision appears an effective and safe treatment for dumping syndrome.

Evaluation of socioeconomic and healthcare disparities on same admission cholecystectomy after endoscopic retrograde cholangiopancreatography among patients with acute gallstone pancreatitis.

BACKGROUND: Despite literature and guidelines recommending same admission cholecystectomy (CCY) after endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute gallstone pancreatitis, clinical practice remains variable. The aim of this study was to investigate the role of clinical and socio-demographic factors in the management of acute gallstone pancreatitis. METHODS: Patients with acute gallstone pancreatitis who underwent ERCP during hospitalization were reviewed from the U.S. Nationwide Inpatient Sample database between 2008 and 2014. Patients were classified by treatment strategy: ERCP + same admission CCY (ERCP + CCY) versus ERCP alone. Measured variables including age, race/ethnicity, Charlson Comorbidity Index (CCI), hospital type/region, insurance payer, household income, length of hospital stay (LOS), hospitalization cost, and in-hospital mortality were compared between cohorts using χ2 and ANOVA. Multivariable logistic regression was performed to identify specific predictors of same admission CCY. RESULTS: A total of 205,012 patients (ERCP + CCY: n = 118,318 versus ERCP alone: n = 86,694) were analyzed. A majority (53.4%) of patients that did not receive same admission CCY were at urban-teaching hospitals. LOS was longer with higher associated costs for patients with same admission CCY [(6.8 ± 5.6 versus 6.4 ± 6.5 days; P < 0.001) and ($69,135 ± 65,913 versus $52,739 ± 66,681; P < 0.001)]. Mortality was decreased significantly for patients who underwent ERCP + CCY versus ERCP alone (0.4% vs 1.1%; P < 0.001). Multivariable regression demonstrated female gender, Black race, higher CCI, Medicare payer status, urban-teaching hospital location, and household income decreased the odds of undergoing same admission CCY + ERCP (all P < 0.001). CONCLUSION: Based upon this analysis, multiple socioeconomic and healthcare-related disparities influenced the surgical management of acute gallstone pancreatitis. Further studies to investigate these disparities are indicated.

How Do Presenting Symptoms and Outcomes Differ by Race/Ethnicity Among Hospitalized Patients With Coronavirus Disease 2019 Infection? Experience in Massachusetts.

BACKGROUND: Population-based literature suggests severe acute respiratory syndrome coronavirus 2 infection may disproportionately affect racial/ethnic minorities; however, patient-level observations of hospitalization outcomes by race/ethnicity are limited. Our aim in this study was to characterize coronavirus disease 2019 (COVID-19)-associated morbidity and in-hospital mortality by race/ethnicity. METHODS: This was a retrospective analysis of 9 Massachusetts hospitals including all consecutive adult patients hospitalized with laboratory-confirmed COVID-19. Measured outcomes were assessed and compared by patient-reported race/ethnicity, classified as white, black, Latinx, Asian, or other. Student t test, Fischer exact test, and multivariable regression analyses were performed. RESULTS: A total of 379 patients (aged 62.9 ± 16.5 years; 55.7% men) with confirmed COVID-19 were included (49.9% white, 13.7% black, 29.8% Latinx, 3.7% Asian), of which 376 (99.2%) were insured (34.3% private, 41.2% public, 23.8% public with supplement). Latinx patients were younger, had fewer cardiopulmonary disorders, were more likely to be obese, more frequently reported fever and myalgia, and had lower D-dimer levels compared with white patients (P < .05). On multivariable analysis controlling for age, gender, obesity, cardiopulmonary comorbidities, hypertension, and diabetes, no significant differences in in-hospital mortality, intensive care unit admission, or mechanical ventilation by race/ethnicity were found. Diabetes was a significant predictor for mechanical ventilation (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.11-3.23), while older age was a predictor of in-hospital mortality (OR, 4.18; 95% CI, 1.94-9.04). CONCLUSIONS: In this multicenter cohort of hospitalized COVID-19 patients in the largest health system in Massachusetts, there was no association between race/ethnicity and clinically relevant hospitalization outcomes, including in-hospital mortality, after controlling for key demographic/clinical characteristics. These findings serve to refute suggestions that certain races/ethnicities may be biologically predisposed to poorer COVID-19 outcomes.

Role of Prophylactic Cholecystectomy After Endoscopic Sphincterotomy for Biliary Stone Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the effectiveness and complication rate of cholecystectomy deferral versus prophylactic cholecystectomy among patients post-endoscopic biliary sphincterotomy for common bile duct stones. BACKGROUND: Although previous reports suggest a decreased risk of biliary complications with prophylactic cholecystectomy, biliary endoscopic cholangiopancreatography (ERCP) with sphincterotomy may provide a role for deferring cholecystectomy with the gallbladder left in situ. METHODS: Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed through August 2019 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Measured outcomes included: mortality, recurrent biliary pain or cholecystitis, pancreatitis, cholangitis, and eventual need for cholecystectomy. Random effects models were used to determine pooled effect size and corresponding 95% confidence intervals (CIs). RESULTS: Nine studies (n = 1605) were included. A total of 53.8% (n = 864) patients had deferred cholecystectomy post-sphincterotomy. Deferral cholecystectomy as compared to prophylactic cholecystectomy resulted in a significant increased risk of mortality [odds raio (OR) 2.56 (95% confidence interval, CI 1.54-4.23); P < 0.0001; I2 = 18.49]. Patients who did not undergo prophylactic cholecystectomy developed more recurrent biliary pain or cholecystitis [OR 5.10 (95% CI 3.39-7.67); P < 0.0001; I2 = 0.00]. Rate of pancreatitis [OR 3.11 (95% CI 0.99-9.83); P = 0.053; I2 = 0.00] and cholangitis [OR 1.49 (95% CI 0.74-2.98); P = 0.264; I2 = 0.00] was unaffected. Overall, 26.00% (95% CI 14.00-40.00) of patients with deferred prophylactic cholecystectomy required eventual cholecystectomy. CONCLUSIONS: Prophylactic cholecystectomy remains the preferred strategy compared to a deferral approach with gallbladder in situ post-sphincterotomy for patients with bile duct stones. Future studies may highlight a subset of patients (ie, those with large balloon biliary dilation) that may not require cholecystectomy.

The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells.

Human respiratory syncytial virus (RSV) is the leading viral cause of acute pediatric lower respiratory tract infections worldwide, with no available vaccine or effective antiviral drug. To gain insight into virus-host interactions, we performed a genome-wide siRNA screen. The expression of over 20,000 cellular genes was individually knocked down in human airway epithelial A549 cells, followed by infection with RSV expressing green fluorescent protein (GFP). Knockdown of expression of the cellular ATP1A1 protein, which is the major subunit of the Na+,K+-ATPase of the plasma membrane, had one of the strongest inhibitory effects on GFP expression and viral titer. Inhibition was not observed for vesicular stomatitis virus, indicating that it was RSV-specific rather than a general effect. ATP1A1 formed clusters in the plasma membrane very early following RSV infection, which was independent of replication but dependent on the attachment glycoprotein G. RSV also triggered activation of ATP1A1, resulting in signaling by c-Src-kinase activity that transactivated epidermal growth factor receptor (EGFR) by Tyr845 phosphorylation. ATP1A1 signaling and activation of both c-Src and EGFR were found to be required for efficient RSV uptake. Signaling events downstream of EGFR culminated in the formation of macropinosomes. There was extensive uptake of RSV virions into macropinosomes at the beginning of infection, suggesting that this is a major route of RSV uptake, with fusion presumably occurring in the macropinosomes rather than at the plasma membrane. Important findings were validated in primary human small airway epithelial cells (HSAEC). In A549 cells and HSAEC, RSV uptake could be inhibited by the cardiotonic steroid ouabain and the digitoxigenin derivative PST2238 (rostafuroxin) that bind specifically to the ATP1A1 extracellular domain and block RSV-triggered EGFR Tyr845 phosphorylation. In conclusion, we identified ATP1A1 as a host protein essential for macropinocytic entry of RSV into respiratory epithelial cells, and identified PST2238 as a potential anti-RSV drug.

Pancreatic cyst fluid glucose in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Recently, low levels of intracystic glucose acquired with EUS-guided pancreatic cyst fluid sampling have been shown to help to differentiate mucinous from nonmucinous cystic neoplasms. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic characteristics of pancreatic cyst fluid glucose compared with carcinoembryonic antigen (CEA) for pancreatic cystic lesions. METHODS: Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines and meta-analysis analyzed according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve for intracystic glucose or CEA alone or combination testing. RESULTS: Eight studies (609 lesions; mean patient age, 63.56 ± 2.75 years; 60.36% women) were included. The pooled sensitivity for pancreatic cyst fluid glucose was significantly higher compared with CEA alone (91% [95% confidence interval {CI}, 88-94; I2 = .00] vs 56% [95% CI, 46-66; I2 = 537.14]; P < .001) with no difference in specificity (86% [95% CI, 81-90; I2 = 24.16] vs 96% [95% CI, 90-99; I2 = 38.06]; P > .05). Diagnostic accuracy was significantly higher for pancreatic cyst fluid glucose versus CEA alone (94% [95% CI, 91-96] vs 85% [95% CI, 82-88]; P < .001). Combination testing with pancreatic cyst fluid glucose and CEA did not improve the diagnostic accuracy compared with glucose alone (97% [95% CI, 95-98] vs 94% [95% CI, 91-96]; P > .05). CONCLUSIONS: Low pancreatic cyst fluid glucose was associated with a high sensitivity and specificity with significantly improved diagnostic accuracy compared with CEA alone for the diagnosis of mucinous versus nonmucinous pancreatic cystic lesions.

Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs). METHODS: Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). RESULTS: Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P < .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I2 = 86.74%), 91% (95% CI, 72-98; I2 = 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P < .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P < .001). CONCLUSIONS: Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone.

Efficacy and safety of peroral cholangioscopy with intraductal lithotripsy for difficult biliary stones: a systematic review and meta-analysis.

BACKGROUND : Peroral cholangioscopy with intraductal lithotripsy facilitates optically guided stone fragmentation of difficult biliary stones refractory to conventional endoscopic therapy. The aim of this study was to evaluate the efficacy and safety of peroral cholangioscopy with intraductal lithotripsy for difficult biliary stones. METHODS : Searches of PubMed, EMBASE, Web of Science, and Cochrane databases were performed in accordance with PRISMA and MOOSE guidelines. Measured outcomes included overall fragmentation success, single-session fragmentation and duct clearance, and rate of adverse events. Sensitivity and subgroup analyses were performed based upon cholangioscopy technique and type of lithotripsy (laser versus electrohydraulic). Heterogeneity was assessed with I 2 statistics. Publication bias was ascertained by funnel plot and Egger regression testing. RESULTS : 35 studies were included with 1762 participants (43.4 % men; mean age 61.5 [standard deviation (SD) 11.0]). Prior cholecystectomy had been performed in 37 % of patients, with a mean number of 1.6 (SD 0.5) ERCPs performed prior to lithotripsy. Mean stone size was 1.8 (SD 0.3) cm. Peroral cholangioscopy with intraductal lithotripsy achieved an overall stone fragmentation success of 91.2 % (95 %CI 88.1 % - 93.6 %; I 2 = 63.2 %) with an average of 1.3 [SD 0.6] lithotripsy sessions performed. Complete single-session fragmentation success was 76.9 % (95 %CI 71.6 % - 81.4 %; I 2 = 74.3 %). The adverse events rate was 8.9 % (95 %CI 6.5 % - 12.2 %; I 2 = 60.6 %). Mean procedure time for peroral cholangioscopy was 67.1 (SD 21.4) minutes. There was no difference in overall fragmentation rate or adverse events; however, laser lithotripsy was associated with a higher single-session fragmentation rate and shorter procedure time compared with electrohydraulic lithotripsy. CONCLUSIONS : Peroral cholangioscopy with intraductal lithotripsy appears to be a relatively safe and effective modality for difficult biliary stones.

Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis.

BACKGROUND: Hybrid endoscopic submucosal dissection (ESD) is increasingly utilized to overcome the complexity of conventional ESD. This systematic review and meta-analysis evaluated the efficacy and safety of hybrid ESD for treatment of colorectal lesions. METHODS: Search strategies were developed in accordance with PRISMA guidelines. Pooled proportions were calculated with rates estimated using random effects models. Measured outcomes included en bloc resection, procedure-associated complications, recurrence, and need for surgery. Subgroup analyses were performed to compare effectiveness of conventional versus hybrid ESD. RESULTS: 16 studies (751 patients) were included with a mean (standard deviation [SD]) lesion size of 27.96 (10.55) mm. En bloc resection rate was 81.63 % (95 % confidence interval [CI] 72.07 - 88.44; I2  = 80.89). Complications, recurrences, and need for surgery occurred in 7.74 % (95 %CI 4.78 - 12.31; I2  = 65.84), 4.52 % (95 %CI 1.40 - 13.65; I2  = 76.81), and 3.64 % (95 %CI 1.76 - 7.37; I2  = 15.52), respectively. Mean procedure duration was 48.83 (22.37) minutes. On subgroup analyses comparing outcomes for conventional (n = 1703) versus hybrid ESD (n = 497), procedure duration was significantly shorter for hybrid ESD (mean difference 18.45 minutes; P = 0.003), with lower complication rates (P = 0.04); however, hybrid ESD had lower en bloc resection rates (P < 0.001). There was no difference in rates of recurrence or surgery (P > 0.05). CONCLUSION: While hybrid ESD was safe and effective for removal of colorectal lesions, with shorter procedure duration, fewer complications, and no difference in recurrence versus conventional ESD, hybrid ESD was associated with a lower en bloc resection rate.