Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by increased red blood cell production, with high risk of venous and arterial thrombosis. Mutations in the JAK2 gene, particularly JAK2 V617F, play a central role in its pathogenesis. Ropeginterferon alfa-2b is a novel long-acting interferon showing promise in managing PV through hematologic and molecular control. This study aimed to evaluate the efficacy and safety of Ropeginterferon alfa-2b in patients with PV based on a systematic review and meta-analysis of available clinical trials. A systematic search was conducted across PubMed, Cochrane Library, Web of Science, Google Scholar, and Scopus on May 8, 2025. Randomized controlled trials (RCTs) assessing Ropeginterferon alfa-2b in PV were included. The PRISMA guidelines were followed, and the protocol was registered in PROSPERO (CRD420251051466). Quality assessment was performed using RoB 2.0 and ROBINS-I tools. A random-effects model was applied using R software. Eight studies involving 761 patients were included and only six studies included in single arm meta-analysis with 328 patients. The pooled proportion of complete hematological response at 12 months was 0.63 (95% CI [0.51–0.73]), with high heterogeneity. Reductions in JAK2 V617F allele burden were significant (MD: 26.57, 95% CI [13.49–39.65]). Molecular response was achieved in 25% (95% CI [0.04–0.70]) of patients. The most common adverse events were elevated liver enzymes (AST: 0.28; ALT: 0.32), influenza-like illness (0.11), and anemia (0.09), with unresolved heterogeneity in all outcomes. Ropeginterferon alfa-2b shows promising efficacy in achieving hematological and molecular responses in patients with PV. However, notable heterogeneity and safety concerns, particularly liver-related adverse effects, warrant further investigation in large-scale trials. Graphical Abstract

Objective: This meta-analysis aims to compare the efficacy and safety of tadalafil and silodosin as medical expulsive therapy (MET) for lower ureteric stones below 10 mm. The study also assesses the incidence of adverse effects associated with each drug. Methods: A comprehensive search of electronic databases was conducted up to October, 2024. The study included randomized controlled trials (RCTs) and cohort studies that compared tadalafil and silodosin in patients with lower ureteric stones (5-10 mm). The primary outcomes assessed were stone expulsion time (SET), stone expulsion rate (SER), and adverse effects. Data were analyzed using a random-effects model for heterogeneity and a fixed-effect model for non-heterogeneity.Results: Eight studies involving 797 patients were included. The pooled analysis showed no significant difference in SET between tadalafil and silodosin (MD = 0.15, 95% CI [-0.28, 0.57], p=0.50), with significant heterogeneity. Similarly, the pooled analysis showed no significant difference in SER between the two drugs (RR = 0.92, 95% CI [0.80 to 1.05], p=0.22), with heterogeneity. However, after excluding one study, silodosin was favored over tadalafil for SER (RR 0.88, 95% CI [0.79 to 0.98], p=0.02). There were no significant differences in headache, backache, or dizziness. Silodosin was associated with a higher incidence of orthostatic hypotension, but this was resolved by excluding one study. A significant difference for abnormal ejaculation favored tadalafil (RR = 0.16, 95% CI [0.09 to 0.29], p=0.01).Conclusions: While the pooled results initially showed no significant difference in SET and SER, silodosin demonstrated a superior stone expulsion rate after adjusting for heterogeneity silodosin showed a trend towards shorter SET. However, silodosin was associated with a higher risk of orthostatic hypotension and abnormal ejaculation. Further high-quality RCTs with larger sample sizes are needed to confirm these findings.

Background Propofol is the most commonly used intravenous anesthetic for endoscopic surgery, although it comes with various adverse effects. Research indicates that Remimazolam, which is considered a safe general anesthetic, is being increasingly adopted as an alternative to propofol in clinical settings. Our meta-analysis sought to evaluate whether the rate of adverse reactions associated with Remimazolam in gastrointestinal endoscopic procedures is acceptable, and whether its surgical success rate is at least comparable to that of propofol. Methods Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched five electronic databases (PubMed, Scopus, Cochrane Library, Embase, and Web of Science) to identify eligible studies published up to January 2025. Using R version R.4.4, we reported outcomes as risk ratios (RRs) or mean differences (MDs) and confidence intervals (CIs). A P-value of ≤ 0.05 is considered statistically significant. Results Our meta-analysis included 37 studies encompassing 8533 patients. The results, analyzed using a random effects model, demonstrated no statistically significant difference in induction time between the two sedative groups, with an overall MD of 0.11 min (95% [- 0.10; 0.31], p = 0.2977). Patients in the Remimazolam group experienced longer total sedation times than those receiving Propofol, with an MD of 1.84 min (95% CI [0.61; 3.07], p = 0.0033). The pooled analysis indicated low heterogeneity (I² = 4.2%). There was no statistically significant difference between the two sedatives in procedure time, with an MD of 0.16 (95% CI: [−0.13; 0.45], p = 0.2689). The pooled analysis displayed moderate heterogeneity (I² = 43.5%, p = 0.0052). Conclusion Remimazolam has demonstrated safety, showing a reduced incidence of hypotension, bradycardia, respiratory depression, and hypoxemia compared to propofol. However, efficacy outcomes including the induction time and total procedure time were comparable between the two groups. However, the results were heterogeneous, which could be due to variability in the perfumed procedures, co-analgesics or dosing.

Background: Parkinson’s disease (PD) is clinically heterogeneous, yet the genetic architecture underlying this heterogeneity remains incompletely understood. We examined the genetic correlates of four complementary PD subtyping frameworks: the clinical motor subtype (tremor-dominant [TD] vs. postural instability/gait difficulty [PIGD]), alpha-synuclein seed amplification assay status (SAA+ vs. SAA−), the pathological subtype (brain-first vs. body-first, based on the presence of REM sleep behavior disorder), and the data-driven subtype (diffuse malignant [DM] vs. mild-motor predominant [MMP] vs. intermediate [IM]). Methods: We analyzed 1390 PD patients from the Parkinson’s Progression Markers Initiative (PPMI) with genotypes available for seven PD-associated genes (LRRK2, GBA1, SNCA, PRKN, PINK1, PARK7, VPS35), including specific variant resolutions (LRRK2 G2019S, R1441G/C/H; GBA1 N409S, severe variants; SNCAA53T), and APOE (ε2/ε3/ε4 alleles). Genetic variant frequencies were compared across subtypes using chi-square or Fisher’s exact tests with the Benjamini–Hochberg false discovery rate (FDR) correction. Effect sizes were quantified using Cramér’s V. multivariable logistic regression estimated adjusted odds ratios with Wald-based 95% confidence intervals. Results: Among genotyped PD patients, LRRK2 carriers constituted 13.7% (190/1390; 170 G2019S, 18 R1441G/C/H), GBA1 8.6% (119/1390; 96 N409S, 23 severe), and SNCA 2.0% (28/1390; all A53T). APOE ε4 carriers comprised 23.4% (323/1380). SAA-negative patients were markedly enriched for LRRK2 variants (37.1% vs. 10.2%, p = 3.7 × 10⁻¹⁹, q < 0.001, V = 0.25), specifically G2019S (28.5% vs. 9.6%, p = 4.9 × 10⁻¹¹, q < 0.001) and R1441G/C/H (7.9% vs. 0.5%, p = 2.7 × 10⁻¹², q < 0.001). Body-first PD was enriched for GBA1 carriers (12.3% vs. 6.7%, p = 0.004, q = 0.021) and had less LRRK2 carriers (7.9% vs. 15.0%, p = 0.002, q = 0.013). The DM subtype had the highest GBA1 frequency (14.0% vs. MMP 5.9%, p < 0.001, q = 0.003). After FDR correction, 10 out of 48 univariate tests remained significant. Clinical subtypes (TD vs. PIGD) showed only nominal LRRK2 differences that did not survive FDR correction. The APOE genotype did not differ across any framework. Conclusions: PD subtypes defined by alpha-synuclein pathology (SAA), pathological onset pattern (brain-first/body-first), and data-driven classification (DM/MMP/IM) show distinct genetic profiles that survive multiple comparison correction. LRRK2 variants strongly associate with SAA negativity (V = 0.25); GBA1 variants associate with the severe body-first onset and the diffuse malignant subtype.