Candela Romano

Keloids are pathological scars causing pain, pruritus, and emotional distress. While common treatments exist, emerging options such as insulin and botulinum toxin A (BTX-A) are underrepresented in comparative analyses. This network meta-analysis (NMA) aimed to evaluate the efficacy and safety profiles of various intralesional therapies for keloid scars. A PRISMA-guided search across seven databases was conducted on July 2025 and preregistered on PROSPERO (CRD420251088758). Included studies were randomized, non-randomized, and crossover trials of intralesional therapies. Pairwise and NMA were conducted for efficacy (keloid size/volume reduction), recurrence, and safety (adverse effects). Treatment rankings were based on surface under the cumulative ranking curve (SUCRA) scores. Statistical significance was set at (p < 0.05). From 51 studies (3234 participants, 23 interventions), 5-fluorouracil (5-FU) + corticoids significantly improved keloid reduction compared to corticoids alone (RR = 1.59; 95% CI: 1.31-1.92; p < 0.01), with 5-FU + corticoids + YAG:Laser (RR = 2.73; 95% CI: 1.36-5.48; p < 0.01) showing an even greater effect. SUCRA values indicated that 5-FU + corticoids + YAG:Laser (0.95), vitamin D + platelet rich plasma (0.83), and 5-FU + corticoids (0.78) had the highest probability of effectiveness. For recurrence, no significant differences were found across interventions, suggesting insufficient evidence. Regarding adverse effects, a significant risk reduction was found for BTX-A (RR = 0.29; 95% CI: 0.09-0.95; p = 0.04) and Verapamil (RR = 0.35; 95% CI: 0.14-0.84; p = 0.01) compared to corticoids; others showed no significant effects. This NMA provides a comparative overview, indicating that combination therapies, most notably 5-FU + corticoids + YAG:Laser, offer the greatest benefit. While data for novel agents (insulin and BTX-A) suggest potential, further research with standardized methodologies and longer-term follow-up is crucial to define optimal treatment algorithms.

Background: Corticosteroids remain the cornerstone of therapy for steroid-sensitive nephrotic syndrome (SSNS), yet the optimal dosing strategy, single daily versus divided doses, remains uncertain. Methods: We conducted a systematic review of studies comparing once-daily and divided-dose prednisolone in children with SSNS. Three randomized controlled trials and one non-randomized study were included, enrolling a total of 288 patients. Primary outcomes were time to remission and relapse frequency; secondary outcomes included hypothalamic–pituitary–adrenal (HPA) axis suppression and adverse events. Results: Overall, remission rates were comparable between single and divided dosing. In relapse settings, one trial showed faster remission with split dosing (by 1–2 days), though without differences in relapse frequency or safety. In first-episode disease, single daily dosing was associated with less HPA axis suppression and a longer time to first relapse. Adverse event profiles were similar across regimens. Conclusions: Single-dose and split-dose prednisolone regimens demonstrate comparable remission efficacy in children with SSNS. Divided dosing may shorten remission by 1–2 days during relapse episodes, but this small benefit must be weighed against the greater HPA-axis suppression observed with multi-dose schedules. Given the heterogeneity and small sample sizes of available trials, the current evidence remains insufficient to establish superiority. Larger multicenter RCTs with standardized protocols and longer follow-up are needed to provide more definitive guidance. Graphical A higher resolution version of the Graphical abstract is available as Supplementary information

Background: Huntington’s disease (HD) causes progressive motor dysfunction, with chorea as its hallmark symptom. Vesicular monoamine transporter 2 (VMAT 2) inhibitors (tetrabenazine, deutetrabenazine, valbenazine) are established symptomatic therapies, while dopamine stabilizers (pridopidine, ordopidine) are emerging therapies, but their net benefit and safety remain uncertain. Methods: Seven databases were searched through May 2025 following PRISMA guidelines. Random effects meta-analyses calculated mean differences (MDs) for the Unified Huntington Disease Rating Scale total motor score (UHDRS TMS) and total maximal chorea score (TMC), plus risk ratios (RRs) for adverse events (AEs). Trial Sequential Analysis (TSA) applied a Lan DeMets O’Brien Fleming α spending function with 80% power. Results: Seven randomized trials (1431 participants) met inclusion criteria. VMAT 2 inhibitors significantly improved motor outcomes versus placebo (UHDRS TMS: MD −3.80, 95% CI −5.76 to −1.83; TMC: MD −3.05, 95% CI −3.84 to −2.26; both I² = 0%). Dopamine stabilizers produced no meaningful change (UHDRS TMS: MD −0.98, 95% CI −2.48 to 0.51; I² = 32%). Neither class increased total AEs (VMAT 2: RR 1.21, 95% CI 0.99 to 1.48; dopamine stabilizers: RR 1.05, 95% CI 0.92 to 1.20; both I² = 0%). TSA confirmed robust evidence for VMAT 2 benefits on TMC but indicated additional data are required to verify dopamine stabilizer effects on UHDRS TMS. Trial sequential analysis confirmed the reliability of VMAT2 for TMC; however, the sample size was insufficient to draw conclusions about the effects of dopamine stabilizers on UHDRS TMS or their safety outcomes, indicating that additional data are needed. Conclusions: VMAT-2 inhibitors may suggest potential improvements in motor symptoms in Huntington’s disease, while current evidence does not demonstrate a significant benefit of dopamine stabilizers. The safety profiles of both treatments appear generally comparable to placebo. Further rigorous and long-term studies are required to better establish their efficacy and safety.