Nayfeh, Tarek

Abstract We aim to compare the benefits, harms, and costs of multiple plastic stents (MPS) versus covered self-expandable metallic stents (CSEMS) in the treatment of benign biliary strictures (BBS). A comprehensive database search through June 6, 2024 identified randomized controlled trials (RCT) involving adult patients with BBS comparing MPS to CSEMS in terms of stricture resolution, recurrence, technical success, number of required procedures and stents, treatment duration, all-cause mortality, adverse events, and stent migration. We utilized the Cochrane Risk of Bias (RoB) tool2 for study quality assessment. Meta-analysis following the random effects model was performed. After screening 365 references, we included 7 RCTs (high RoB) involving 594 patients. Most reported stricture etiology is chronic pancreatitis (52.4%), followed by orthotopic liver transplant (40.5%). Compared with MPS, CSEMS achieved similar efficacy and safety. However, CSEMS required fewer procedures (mean difference [MD]: −1.84 [−2.56 to −1.11]; I2 = 76%) and stents (MD: −6.04 [−9.55 to −2.52]; I2 = 93%), amounting for shorter duration of treatment (MD: −119.02 days [−137.41 to −100.62]; I2 = 96%) and savings in costs between 41 and 57% with absolute savings of 4,019$ to 9,192$ favoring CSEMS. All outcomes had a low to very low certainty of evidence (CoE), except for technical success and stricture resolution (moderate CoE). Our analysis suggests that CSEMSs are comparable to MPSs in terms of efficacy and safety. However, it shows that CSEMSs are more cost-effective. Sample size calculations from our analyses can guide the design of future studies to validate the safety profiles and determine the feasibility of the two modalities.

Background Bacterial infections remain a major global health burden, causing significant morbidity and mortality. Despite ongoing advances, prompt diagnosis is still hampered by nonspecific host biomarkers and the inherently slow turnaround of traditional microbiological cultures. These limitations often delay the initiation of appropriate treatments. In recent years, affinity-based proteomic approaches have been explored to address this gap. Among them, the Proximity Extension Assay (PEA) has emerged as a promising multiplexed protein quantification tool, capable of simultaneously measuring hundreds of immune and inflammatory proteins with high sensitivity from minimal sample volumes. Such technologies hold the potential to identify novel biomarkers, thereby improving both diagnosis and patient management in bacterial infections. Main body In this systematic scoping review, we examined studies applying PEA-based proteomics to adult bacterial infections. Out of the records screened, ten studies met inclusion criteria. Most were conducted in Europe and North America, relied primarily on plasma samples, and employed commercially available panels enriched for immune and inflammatory mediators. Study quality varied, with some evidence of variability and potential risk of bias. Across the 379 proteins investigated, a subset of proteins were consistently associated with bacterial infections across multiple clinical contexts, whereas others showed limited or no associations. Conclusions Current applications of PEA-based proteomics in adult bacterial infections is limited and largely exploratory. Rather than supporting immediate clinical translation, the available evidence suggests the value of PEA-based approaches for informing biomarker discovery. Future research should prioritize well-designed, longitudinal, and pathogen-stratified studies in clinically relevant settings to strengthen evidence robustness and support the rational development of proteomics-informed diagnostic and translational strategies.

Lay Summary This meta-analysis of 8 randomized controlled trials compares the effectiveness of using high-definition scopes with virtual chromoendoscopy vs dye chromoendoscopy for detecting dysplasia in inflammatory bowel disease patients. Overall, the odds of dysplasia detection were not significantly different between dye chromoendoscopy and virtual chromoendoscopy.

Abstract Background Partial breast irradiation (PBI) is an effective treatment for early-stage breast cancer. However, evidence comparing different PBI modalities is limited. Methods This trial emulation uses electronic health records from a multi-state large tertiary health system. Three PBI modalities were compared: proton radiation therapy, photon radiation therapy, and applicator-based brachytherapy. Inverse probability weighting (IPW) was used to balance confounders. The primary outcome was ipsilateral breast recurrence (IBR). Results Between 2013 and 2023, 1041 women with early-stage breast cancer were treated with PBI. Of these, 1026 patients were included in the analyses. The median age was 66 years; 22.51% had ductal carcinoma in situ (DCIS), and 97.56% were estrogen receptor positive. With median follow-up of 38.2 months, the rate of IBR in the overall group was 3.05% (95% confidence interval [CI] = 1.99% to 4.65%) at 3 years. After IPW, compared with photon PBI, the hazard ratio for IBR for proton PBI was 2.11 (95% CI = 0.70 to 6.33) and for brachytherapy, 3.86 (95% CI = 1.39 to 10.69). Compared with proton PBI, the hazard ratio for IBR for brachytherapy was 1.83 (95% CI = 0.88 to 3.81). IBR risk was similar across PBI modalities for patients with tumor size ≤ 10 mm and in patients treated for DCIS. Among patients with tumor size >10 mm, the hazard ratio for IBR for brachytherapy was 7.64 (95% CI = 1.64 to 35.58) and 3.59 (95% CI = 1.22 to 10.56) relative to photons and protons, respectively. Conclusion PBI with applicator-based brachytherapy was associated with higher IBR than photon or proton PBI in patients with tumor size > 10 mm, suggesting the need for more careful PBI patient selection for this modality.

Background and Aims: With rapid changes in the management landscape of chronic hepatitis B (CHB), this technical systematic review addresses 4 critical Population, Intervention, Comparator, Outcome (PICO) questions to provide guidance to the formulation of recommendations to the 2025 AASLD practice guideline for management of CHB. Approach: The review was reported in accordance with PRISMA guidelines. Outcomes were evaluated across 4 key PICOs: (1) antiviral therapy for prevention of horizontal HBV transmission in high-risk groups, (2) antiviral therapy versus observation for persons in the immune-tolerant phase, (3) discontinuation versus continuation of nucleos(t)ide analogue therapy in HBeAg-negative individuals with undetectable HBV DNA, and (4) hepatocellular carcinoma (HCC) surveillance in non-cirrhotic individuals with HBsAg clearance or co-infections with HCV, HDV, or HIV. Results: For PICO 1, limited evidence suggests antiviral therapy may reduce horizontal transmission risk, though with low certainty. PICO 2 analyses reveal uncertain benefits of treating persons in the immune-tolerant phase, with very low certainty due to heterogeneity and bias. PICO 3 analyses demonstrate that discontinuing antiviral therapy in persons who are HBeAg negative with undetectable HBV DNA increases HBsAg loss rates (OR: 12.65, 95% CI: 1.58–101.51) but carries moderate risks of virologic relapse (OR: 47.17, 95% CI: 2.79–797.35) and clinical flares. PICO 4 analyses on several cohort studies showed that in patients co-infected with HCV, HBV, or HIV, the annual incidence of HCC was higher than the level where screening becomes cost-effective, suggesting that regular liver cancer screening could be beneficial for these patients. Conclusions: Despite low certainty, the findings support shared decision-making in high-risk horizontal transmission scenarios or in treating individuals in the immune tolerance phase, caution in discontinuing antiviral therapy in virologically suppressed individuals without HBsAg loss, and tailored HCC surveillance for those with co-infection or cirrhosis.

Abstract Artificial intelligence (AI) and mucosal exposure devices like Endocuff have independently improved the adenoma detection rate (ADR) during colonoscopy. This meta-analysis evaluated the combined effect of Endocuff and AI versus AI alone on colorectal neoplasia detection rates. We searched PubMed, Embase, and Web of Science for randomized controlled trials (RCTs) comparing the impact of Endocuff+AI versus AI alone on colorectal neoplasia detection. Primary outcome was ADR; secondary outcomes included advanced adenoma detection rate (AADR), sessile serrated lesion detection rate (SSLDR), cecal intubation time, and withdrawal time. Pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Three RCTs with 2404 subjects were included (n = 1198 Endocuff+AI vs. n = 1206 AI alone). ADR was significantly higher in the Endocuff+AI group than in the AI alone group (54% vs. 48%, respectively) (RR 1.12, 95% CI 1.03–1.21, P = 0.01, I2 = 0%). There was a trend toward higher AADR (12.3% vs. 10%, RR 1.23, 95% CI 0.96–1.59, P = 0.10, I2 = 17%) and SSLDR (17.6% vs. 15.5%, RR 1.16, 95% CI 0.96–1.40, P = 0.13, I2 = 0%) in the Endocuff+AI group compared with the AI alone group, but it did not reach statistical significance. Both cecal intubation time (MD -0.61 minutes; 95% CI -1.54–0.33; P = 0.20; I2 = 87%) and withdrawal time (MD -0.42 minutes; 95% CI -1.01–0.17; P = 0.17, I2 = 60%) were similar between the two groups. Endocuff combined with AI was superior to AI alone in improving the adenoma detection rate without increasing intubation or withdrawal times.

Abstract Introduction Case reports and series are critical to guide initial decision-making in a pandemic, but may have lower rigor because of the need to publish them quickly. This meta-epidemiologic study compares the methodological quality of case series that described the acute coronavirus disease 2019 (COVID-19) pandemic in 2020 versus those that described long-haul cases. Methods We conducted a systematic review in multiple databases for long-haul case series and reports. We identified early cases of acute COVID-19 synthesized in published systematic reviews. We evaluated the methodological quality by pairs of independent reviewers using a tool dedicated for appraising case series. Results We included 239 original case series (81 published in the first year of the pandemic and 158 published later describing long-haul COVID). The methodological quality of both groups of case series was very good (80–100% of series satisfying quality items) except for two items, the selection approach of cases included in the series and ruling out other causes that can explain the main finding described in the series. The appraisal tool demonstrated high agreement and reliability between reviewers. Conclusion The methodological quality of modern case series is high, except for two quality items that represent an area for potential for improvement for authors of case series describing future pandemics.

INTRODUCTION: The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on colonoscopy bowel preparation is unclear. METHODS: We searched multiple databases for studies comparing bowel preparation quality between GLP-1RA users and the control group. Using a random-effects model, we calculated pooled odds ratios and mean differences with 95% confidence intervals (CIs). Inadequate bowel preparation (IBP) rate was the primary outcome, and Boston Bowel Preparation Scale mean score was the secondary outcome. RESULTS: Five studies with 10,833 patients (n = 5,434 GLP-1RAs vs n = 5,399 control) were included. The IBP rate was higher in the GLP-1RAs group compared with the control group (odds ratios 2.10, 95% CI 1.41–3.13, P = 0.0003). Furthermore, the mean Boston Bowel Preparation Scale score was lower in the GLP1-RAs group compared with the control group (mean differences −0.34; 95% CI −0.51, −0.17; P = 0.0001). DISCUSSION: Our findings suggest that using GLP-1RA increases the risk of IBP.

Abstract Background Studies aiming to synthetize data from literature are helpful to valid the robustness of associations, to assess the quality of the data, and, eventually, to propose recommendations. This is particularly evident for the huge amount of data reported for SARS-CoV-2. The aim of this study was to perform an umbrella review to identify the strength and validity of associations between variants of concern (VOCs) and pre-specified clinical outcomes in COVID-19 patients. Table 1 Effect size measures reported in the studies included in the review, divided by outcome. Acronyms: CI, confidence interval; OR: odds ratio; RR, risk ratio; cCFR, confirmed case-fatality risk; HFR, hospitalization-fatality risk; N/A, not available Methods An umbrella review according to the principles to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed searching multiple databases in January 2024. Peer reviewed systematic reviews considering ≥ 2 VOCs with a clinical outcome among death, hospitalization, severe disease, admission to intensive care unit (ICU), and mechanical ventilation were included. Data on study population and measures of association between clinical outcome and VOCs were considered. The quality of the studies was assessed through the AMSTAR-2 tool. The effect size measures with the confidence interval for each association between VOCs and clinical outcomes were reported. Subgroup analyses were performed, if possible. A citation matrix was used to assess the overlap between the systematic reviews included. Table 2 Risk of bias assessment of the included systematic reviews using the AMSTAR-2 score. In bold the key domains. Results A total of 11 studies were included in our review. 24 total comparison were considered, most regarding Omicron versus Delta (19/24), where Omicron was always associated with better clinical outcomes than Delta. The overall quality of the studies was low. None of the reviewed studies incorporated consideration of risk factors other than VOCs in evaluating clinical outcomes. The overlap between the included reviews is low, only 10% of them having a significant overlap ( > 15%). Conclusion Our umbrella review shows the lower hazard on human health of the Omicron compared to Delta variant. However, the quality of the reviews included were generally low and there is a lack of correction with other risk factors such as comorbidities and vaccination status. While our review provides valuable insights into the association between VOCs and clinical outcomes of SARS-CoV-2 infection, further research incorporating risk factor analysis and ensuring methodological rigor is warranted. Disclosures All Authors: No reported disclosures