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.

Respiratory Syncytial Virus Vaccine Design Using Structure-Based Machine-Learning Models.

When designing live-attenuated respiratory syncytial virus (RSV) vaccine candidates, attenuating mutations can be developed through biologic selection or reverse-genetic manipulation and may include point mutations, codon and gene deletions, and genome rearrangements. Attenuation typically involves the reduction in virus replication, due to direct effects on viral structural and replicative machinery or viral factors that antagonize host defense or cause disease. However, attenuation must balance reduced replication and immunogenic antigen expression. In the present study, we explored a new approach in order to discover attenuating mutations. Specifically, we used protein structure modeling and computational methods to identify amino acid substitutions in the RSV nonstructural protein 1 (NS1) predicted to cause various levels of structural perturbation. Twelve different mutations predicted to alter the NS1 protein structure were introduced into infectious virus and analyzed in cell culture for effects on viral mRNA and protein expression, interferon and cytokine expression, and caspase activation. We found the use of structure-based machine learning to predict amino acid substitutions that reduce the thermodynamic stability of NS1 resulted in various levels of loss of NS1 function, exemplified by effects including reduced multi-cycle viral replication in cells competent for type I interferon, reduced expression of viral mRNAs and proteins, and increased interferon and apoptosis responses.

Endoscopic Management of Gastric Band Erosion: a Systematic Review and Meta-Analysis.

BACKGROUND: Gastric band erosion may be seen in up to 3% of patients. Endoscopic intervention has become increasingly utilized due to its minimally invasive nature. The purpose of this study was to perform a systematic review and meta-analysis to examine the role of endoscopic removal for eroded gastric bands. METHODS: Individualized search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases in accordance with PRISMA and MOOSE guidelines. Outcomes included technical success, clinical success, procedure duration, adverse events, and surgical conversion. Pooled proportions were analyzed using random effects models. Heterogeneity and publication bias was assessed with I2 statistics and funnel plot asymmetry using Egger and Begg tests. Meta-regression was also performed comparing outcomes by endoscopic tools. RESULTS: Ten studies (n=282 patients) were included in this meta-analysis. Mean age was 40.68±7.25 years with average duration of band placement of 38.49±19.88 months. Pre-operative BMI was 42.76±1.06 kg/m2 with BMI of 33.06±3.81 kg/m2 at time of band erosion treatment. Endoscopic removal was attempted in 240/282 (85.11%) of cases. Pooled technical and clinical success of the endoscopic therapy was 86.08% (95% CI: 79.42-90.83; I2=28.62%) and 85.34% (95% CI: 88.70-90.62; I2=38.56%), respectively. Mean procedure time for endoscopic removal was 46.47±11.52 min with an intra-operative adverse event rate of 4.15% (95% CI: 1.98-8.51; I2=0.00%). Post-procedure-associated adverse events occurred in 7.24% (CI: 4.46-11.55; I2=0.00%) of patients. Conversion to laparotomy/laparoscopy occurred in 10.54% (95% CI: 6.12-17.54) of cases. CONCLUSION: Endoscopic intervention is a highly effective and safe modality for the treatment of gastric band erosion.

Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis.

Background and study aims Recurrent biliary stent occlusion and tumor ingrowth remain a major concern among patients with malignant biliary obstruction (MBO) with significant impact on patient morbidity and survival. Intraductal radiofrequency ablation (RFA) has emerged as a promising treatment that seeks to extend stent patency. This study aimed to evaluate the impact of RFA on overall survival (OS) and stent patency among patients with unresectable MBO. Methods A comprehensive search of electronic databases was performed for randomized controlled trials (RCTs) comparing RFA plus biliary stent (RFA+S) versus biliary stent alone (S-alone). Outcomes assessed included overall survival, stent patency, and adverse events (AEs) with mean difference (MD) calculated from pooled proportions. Subgroup analyses were performed for hilar strictures and cholangiocarcinoma (CCA). Results Six RCTs (n=439 patients) were included and demonstrated improved survival among patients who received RFA+S (MD 85.80 days; 95% confidence interval [CI] 35.02-136.58; I 2 =97%; P <0.0009). The pooled MD for total stent patency was 22.25 days (95% CI 17.38-61.87; I 2 =97%; P =0.27). There was no difference in AEs between RFA+S vs S-alone ( P >0.05). On subgroup analyses, RFA+S was associated with improved stent patency (MD 76.73 days; 95% CI 50.11-103.34; I 2 =67%; P <0.01) and OS (MD 83.14 (95% CI 29.52-136.77; I 2 =97%; P <0.01] for CCA. For hilar strictures, stent patency was improved among patients with RFA+S [MD 83.71 days (95% CI 24.85-142.56; I 2 =84%; P <0.01]. Conclusions RFA+S improved OS in the treatment of MBO when compared with S-alone. Moreover, the RFA therapy prolonged stent patency in hilar strictures and CCA, with similar rates of AEs.

Correction: Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis.

[This corrects the article DOI: 10.1055/a-2204-8316.].

Diagnostic characteristics of serological-based COVID-19 testing: a systematic review and meta-analysis

Serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promises to assist in assessing exposure to and confirming the diagnosis of coronavirus disease 2019 (COVID-19), and to provide a roadmap for reopening countries worldwide. Considering this, a proper understanding of serologic-based diagnostic testing characteristics is critical. The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic characteristics of serological-based COVID-19 testing. Electronic searches were performed using Medline (PubMed), EMBASE, and Cochrane Library. Full-text observational studies that reported IgG or IgM diagnostic yield and used nucleic acid amplification tests (NAATs) of respiratory tract specimens, as a the reference standard in English language were included. A bivariate model was used to compute pooled sensitivity, specificity, positive/negative likelihood ratio (LR), diagnostic odds ratio (OR), and summary receiver operating characteristic curve (SROC) with corresponding 95% confidence intervals (CIs). Five studies (n=1,166 individual tests) met inclusion criteria. The pooled sensitivity, specificity, and diagnostic accuracy for IgG was 81% [(95% CI, 61-92);I2=95.28], 97% [(95% CI, 78-100);I2=97.80], and 93% (95% CI, 91-95), respectively. The sensitivity, specificity, and accuracy for IgM antibodies was 80% [(95% CI, 57-92);I2=94.63], 96% [(95% CI, 81-99);I2=92.96] and 95% (95% CI, 92-96). This meta-analysis demonstrates suboptimal sensitivity and specificity of serologic-based diagnostic testing for SARS-CoV-2 and suggests that antibody testing alone, in its current form, is unlikely to be an adequate solution to the difficulties posed by COVID-19 and in guiding future policy decisions regarding social distancing and reopening of the economy worldwide.

Gastrointestinal manifestations and associated health outcomes of COVID-19: a brazilian experience from the largest south american public hospital

OBJECTIVES: Brazil has rapidly developed the second-highest number of COVID-19 cases in the world. As such, proper symptom identification, including gastrointestinal manifestations, and relationship to health outcomes remains key. We aimed to assess the prevalence and impact of gastrointestinal symptoms associated with COVID-19 in a large quaternary referral center in South America. METHODS: This was a single-center cohort study in a COVID-19 specific hospital in São Paulo, Brazil. Consecutive adult patients with laboratory confirmed SARS-CoV-2 were included. Baseline patient history, presenting symptoms, laboratory results, and clinically relevant outcomes were recorded. Regression analyses were performed to determine significant predictors of the gastrointestinal manifestations of COVID-19 and hospitalization outcomes. RESULTS: Four-hundred patients with COVID-19 were included. Of these, 33.25% of patients reported ≥1 gastrointestinal symptom. Diarrhea was the most common gastrointestinal symptom (17.25%). Patients with gastrointestinal symptoms had higher rates of concomitant constitutional symptoms, notably fatigue and myalgia (p<0.05). Gastrointestinal symptoms were also more prevalent among patients on chronic immunosuppressants, ACE/ARB medications, and patient with chronic kidney disease (p<0.05). Laboratory results, length of hospitalization, ICU admission, ICU length of stay, need for mechanical ventilation, vasopressor support, and in-hospital mortality did not differ based upon gastrointestinal symptoms (p>0.05). Regression analyses showed older age [OR 1.04 (95% CI, 1.02-1.06)], male gender [OR 1.94 (95% CI, 1.12-3.36)], and immunosuppression [OR 2.60 (95% CI, 1.20-5.63)], were associated with increased mortality. CONCLUSION: Based upon this Brazilian study, gastrointestinal manifestations of COVID-19 are common but do not appear to impact clinically relevant hospitalization outcomes including the need for ICU admission, mechanical ventilation, or mortality.

Approach to endoscopic procedures: a routine protocol from a quaternary university referral center exclusively for coronavirus disease 2019 patients

OBJECTIVES: The present coronavirus disease (COVID-19) pandemic has ushered in an unprecedented era of quality control that has necessitated advanced safety precautions and the need to ensure the adequate protection of healthcare professionals (HCPs). Endoscopy units, endoscopists, and other HCP may be at a significant risk for transmission of the virus. Given the immense burden on the healthcare system and surge in the number of patients with COVID-19, well-designed protocols and recommendations are needed. We aimed to systematically characterize our approach to endoscopic procedures in a quaternary university hospital setting and provide summary protocol recommendations. METHOD: This descriptive study details a COVID-19-specific protocol designed to minimize infection risks to patients and healthcare workers in the endoscopy unit. RESULTS: Our institution, located in São Paulo, Brazil, includes a 900-bed hospital, with a 200-bed-specific intensive care unit exclusively designed for patients with moderate and severe COVID-19. We highlighted recommendations for infection prevention and control during endoscopic procedures, including appropriate triage and screening, outpatient management and procedural recommendations, role and usage of personal protective equipment (PPE), and role and procedural logistics involving COVID-19-positive patients. We also detailed hospital protocols for reprocessing endoscopes and cleaning rooms and also provided recommendations to minimize severe acute respiratory syndrome coronavirus 2 transmission. CONCLUSION: This COVID-19-specific administrative and clinical protocol can be replicated or adapted in multiple institutions and endoscopy units worldwide. Furthermore, the recommendations and summary protocol may improve patient and HCP safety in these trying times.