Jefferson Manoel Borges Martins

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) are cytokines involved in B-cell activation and survival, contributing to the pathogenesis of IgAN. This meta-analysis aimed to evaluate the efficacy, safety, and biomarkers of BAFF- or APRIL-targeted therapies in patients with IgAN. We searched PubMed, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) comparing BAFF- or APRIL-targeted drugs with placebo in adults with IgAN, published up to December 2024 and written in English. Efficacy outcomes were the mean percent change in the 24-hour urine protein-to-creatinine ratio (UPCR) and the mean change in the estimated glomerular filtration rate (eGFR) from baseline. Safety included the incidence of adverse events. The biomarkers we used were changes in serum Gd-IgA1, IgG, IgA, and IgM from baseline. The risk of bias and the certainty of evidence were assessed using RoB v2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). We used the R software version 4.2.1 for statistics. Four Phase II RCTs, including 331 patients, were included, with three studies having a low risk of bias, while there were some concerns regarding one study. Compared to placebo, BAFF- or APRIL-targeted drugs significantly reduced 24-hour UPCR (mean difference [MD] −38.94%; 95% confidence interval [CI] −58.98 to −18.90; P = 0.0001; I² = 0%) and significantly improved the eGFR (MD 7.05 mL/min/1.73 m²; 95% CI 3.83 to 10.27; P < 0.0001; I² = 0%). Adverse events did not significantly differ between the study groups. BAFF- or APRIL-targeted drugs significantly decreased serum Gd-IgA1, IgG, IgA, and IgM compared with placebo, indicating lower immune complex formation and response to treatment. BAFF- or APRIL-targeted therapies appear to be effective and safe in reducing proteinuria in patients with IgAN. CRD42024598157

Patients undergoing transcatheter aortic valve implantation (TAVI) often require long‐term oral anticoagulation (OAC), but it is unclear whether to continue or interrupt OAC during the procedure. This meta‐analysis compares clinical outcomes of continuing versus interrupting OAC during TAVI. PubMed, Embase, and Cochrane Central databases were searched from inception to September 2024 for studies comparing continuation versus interruption of OAC in patients undergoing TAVI with an indication for OAC, including vitamin K antagonists and direct oral anticoagulants. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random‐effects model. Sensitivity analysis was performed using the Hartung‐Knapp‐Sidik‐Jonkman method. Three studies were included, one randomized controlled trial and two cohort studies, with 2773 patients, of whom 1314 (47.4%) continued OAC during TAVI. At a 30‐day follow‐up after TAVI, there were no significant differences between groups in all‐cause mortality (RR 0.74; 95% CI 0.45–1.20; p = 0.22), any bleeding (RR 1.08; 95% CI 0.81–1.43; p = 0.60), and major bleeding (RR 0.90; 95% CI 0.67–1.21; p = 0.48). However, the continued OAC group was associated with a lower stroke rate (RR 0.65; 95% CI 0.42–1.01; p = 0.053), also attested after a sensitivity analysis (RR 0.65; 95% CI 0.47–0.90; p < 0.03). In patients with an indication for OAC undergoing TAVI, uninterrupted anticoagulation is associated with similar thrombotic and hemorrhagic outcomes compared to interrupted OAC. Stroke risk was lower in the continued OAC group, with a significant reduction, as demonstrated in sensitivity analysis.

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. BAFF (B-cell activating factor) and APRIL (A proliferation-inducing ligand) are cytokines involved in B-cell activation and survival, contributing to the pathogenesis of IgAN. This meta-analysis aimed to evaluate the efficacy, safety, and biomarkers of BAFF and APRIL-targeted therapies in patients with IgAN. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered with PROSPERO (CRD42024598157). We searched PubMed, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) comparing BAFF or APRIL-targeted drugs with placebo in adults with biopsy-confirmed IgAN. The efficacy outcomes were the mean percent change in the urine protein to creatinine ratio (UPCR) at 24 hours and the mean change in the estimated glomerular filtration rate (eGFR) from baseline. Safety included the incidence of adverse events. The biomarkers were changes in serum Gd-IgA1, IgG, IgA, and IgM from baseline. We used the R software version 4.2.1 for statistics. Results: Four phase II RCTs including 331 patients were included. Compared to placebo, treatment significantly reduced 24-hour UPCR (mean difference [MD] –38.94%; 95% confidence interval [CI] –58.98 to –18.90; p = 0.0001; I² = 0%) and significantly improved eGFR (MD 7.05 mL/min/1.73 m²; 95% CI 3.83 to 10.27; p<0.0001; I²=0%). The incidence of adverse events did not differ significantly in the treatment and placebo groups. The drug significantly decreased serum Gd-IgA1, IgG, IgA, and IgM compared to placebo. Conclusions BAFF and APRIL-targeted therapies effectively and safely reduce proteinuria in patients with IgAN.

Levetiracetam (LEV) and carbamazepine (CBZ) are effective monotherapies for focal epilepsy in children. However, the best drug remains controversial. Therefore, we performed a systematic review and meta-analysis comparing LEV and CBZ monotherapy in the management of pediatric focal epilepsy (PFE). We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) published until February 2024 comparing LEV and CBZ monotherapy in PFE. Statistical analysis was performed using R version 4.2.2, heterogeneity was assessed using I² statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered significant. The outcomes of interest were seizure freedom, any adverse events, adverse events leading to treatment discontinuation, dermatologic adverse events, and the frequency of at least one seizure, defined as the proportion of patients experiencing one or more seizures during the treatment period. Four RCTs comprising 381 children with a mean age of 7.32 to 9.28 years were included, of whom 186 (48.8%) received LEV monotherapy. There was no significant difference between groups (RR: 1.15; 95% CI 0.88–1.50; p = 0.31; I² = 90%) regarding seizure freedom. The frequency of at least one seizure (RR: 0.71; 95% CI 0.52–0.97; p = 0.03; I² = 8%) and dermatologic adverse events (RR: 0.24; 95% CI 0.09–0.64; p < 0.01; I² = 0%) were both significantly lower in the LEV group. There were no significant differences in the presence of any adverse events (RR: 0.58; 95% CI 0.33–1.01; p = 0.05; I² = 36%) or adverse events leading to treatment discontinuation (RR: 0.67; 95% CI 0.13–3.42; p = 0.63; I² = 30%).Conclusion: In monotherapy, LEV was more advantageous than CBZ for PFE, with a lower frequency of seizures and fewer dermatological adverse events. However, both drugs are equally effective in achieving seizure freedom, adverse events without specification, and those that lead to treatment discontinuation. Our findings have important implications for clinical practice and decision-making in this condition. What is Known: • Both LEV and CBZ are effective monotherapies for pediatric focal epilepsy. • The use of LEV or CBZ monotherapy for the management of children with focal epilepsy remains controversial. What is New: • No significant differences were observed between the LEV and CBZ groups in terms of overall seizure freedom, safety, and tolerance. • However, LEV resulted in a lower frequency of at least one seizure and fewer dermatological adverse events than CBZ.