Giovanni Gosch Berton

Sleep disruption is recognized as a risk factor for Alzheimer’s disease (AD). Both chronic and acute sleep deprivation (SD) may increase cerebrospina

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.

Host–parasite adaptation is crucial for evolutionary success of a parasite. The nematode Angiostrongylus cantonensis has a heterogenic life cycle involving molluscs as intermediate hosts and rats as definitive hosts. Several mollusc species are susceptible hosts of A. cantonensis, allowing the development of first-stage larvae (L1) into third-stage larvae (L3). Changes in the metabolism of infected molluscs have been demonstrated, disturbing regular routes and inducing host defence mechanisms. This study aimed to identify changes in the proteomic content of Phyllocaulis spp. mucus during A. cantonensis infection. Proteins were extracted from the mucus samples of infected and non-infected slugs and identified using liquid chromatography–tandem mass spectrometry. We found 26 up-regulated and 15 down-regulated proteins in infected slugs compared to non-infected slugs. Protein profiles are promising markers of parasite infection, and a better understanding of proteomic profiles during infection may help inform in vivo studies and promote new tools for the non-invasive identification of infected hosts.

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.

Background: Alpha-synucleinopathies are incurable neurodegenerative diseases. Abelson tyrosine kinase inhibitors (Abl TKIs) may be disease-modifying therapies. This systematic review, meta-analysis, and meta-regression evaluated the use of Abl TKIs in their treatment. Methods: We searched PubMed, Embase, and Cochrane databases for trials using Abl TKIs in patients with Parkinson's disease and Lewy body dementia published until July 2023. The outcome was the change in the MDS-UPDRS-III (Movement Disorder Society–Sponsored Revision of the Unified Parkinson's Disease Rating Scale III). DerSimonian-Laird random-effects model was used to calculate the pooled effect estimates. Leave-one-out forest plots were used for the sensitivity analysis, and meta-regression (restricted maximum likelihood) was performed. Results: Five studies (197 patients) were included. Nilotinib 300 mg had an effect size of −1.154 (95% confidence interval [CI], −3.000 to 0.692). Nilotinib 150 mg and bosutinib 100 mg versus placebo yielded 0.82 (95% CI, −3.76 to 5.41). Sensitivity analysis showed that 1 trial changed the significance of the nilotinib 300 mg single-arm analysis (MD = −1.723; 95% CI, −2.178 to −1.268). Meta-regression revealed that lower age (EC = −0.9103, SE = 0.2286, P < 0.0001) and higher baseline MDS-UPDRS-III scores (EC = 0.1210, SE = 0.0168, P < 0.0001) could explain the inefficacy of nilotinib 300 mg. Conclusions: Nilotinib (300 mg) proved effective postsensitivity analysis, unlike lower doses and bosutinib in Parkinson's disease/Lewy body dementia. Abl TKIs showed reduced efficacy in younger, more impaired patients, indicating the need for further testing with higher-potency drugs in patients who have diseases that are in the early stage but with a later onset.