Objective: Nerandomilast, an oral phosphodiesterase‐4 (PDE4) inhibitor, has shown potential in slowing the progression of pulmonary fibrosis. This meta‐analysis evaluated the efficacy and safety of nerandomilast in preserving lung function among patients with pulmonary fibrosis. Methods: MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing nerandomilast with placebo. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Analyses were performed in RevMan 5.4 using random‐effects models with risk ratios (RR) and mean differences (MD) as effect measures. Results: Four RCTs ( n = 2515) were included. Nerandomilast significantly attenuated the decline in forced vital capacity (FVC) compared with placebo (MD: 69.25 mL, 95% CI: 52.1–86.29), but did not improve diffusing capacity for carbon monoxide (DLCO) (MD: 0.84, 95% CI: −0.56 to 2.24). It was associated with a lower pooled risk of all‐cause mortality (RR: 0.68, 95% CI: 0.52–0.88) without increasing adverse events (RR: 1.00, 95% CI: 0.98–1.02) or serious adverse events (RR: 0.93, 95% CI: 0.76–1.14). Conclusion: Nerandomilast appears to slow lung function decline in pulmonary fibrosis without added safety risks. Although a lower pooled risk of mortality was observed, individual trials were not powered for mortality outcomes, and event rates were low; therefore, this finding should be interpreted cautiously. Given the heterogeneity of pulmonary fibrosis phenotypes and trial designs, further large‐scale RCTs should explore standardized outcomes, subgroup effects, and combination strategies with nintedanib or pirfenidone.

Background/objective: HCM is a structural disorder of the myocardium that leads to sudden cardiac death in young adults. We synthesized an updated understanding of the role of Cardiac Myosin Inhibitors (CMIs) in HCM by pooling data from RCTs. Methods: We identified six published RCTs, involving 826 participants. Data were extracted pertaining to study characteristics; primary outcomes of interest–(1) change from baseline in resting left ventricular outflow tract (LVOT) peak gradient, (2) change from baseline in Valsalva LVOT peak gradient, and (3) improvement of ≥1 NYHA class–and secondary outcomes. These were pooled using Review Manager 5.4, employing a random-effects model, and reported as odds ratios (ORs) or mean differences (MDs). Results: We found statistically significant between-group difference favoring CMIs in change from baseline in LVOT peak gradient: at rest (MD −39.33; −53.01 to −25.64), post-Valsalva (MD −48.99; −53.96 to −44.03), and post-exercise (MD −37.11; −44.34 to −29.87); ≥1 NYHA class improvement (OR 4.10; 2.79–6.02), change from baseline in peak oxygen uptake (MD −37.11; −44.34 to −29.87), LVOT gradient ≤30 mm hg (RR 14.89; 7.47–29.67), participants eligible for septal reduction therapy (RR 0.26; 0.18–0.36), and change from baseline in KCCQ-CSS score (MD 8.54; 5.36–11.71). Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. Conclusions: CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT.

Material and methods: We searched several databases using Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and ClinicalTrials.gov. We included only placebo-controlled clinical trials on infants born at less than 32 weeks’ gestation, who were administered enteral vitamin A supplementation. A random effects model was employed to calculate risk ratios and weighted mean differences. Results: A total of five studies with 1715 participants were included in our meta-analysis. No significant reduction was observed in the incidence of moderate-to-severe bronchopulmonary dysplasia [RR = 0.91, 95% CI (0.70, 1.17), P = 0.45], retinopathy of prematurity requiring treatment [RR = 0.94, 95% CI (0.62 to 1.42), P = 0.76], sepsis [RR = 0.96 95% CI (0.74 to 1.24), P = 0.73], mortality RR = 0.86, 95% CI, (0.65 to 1.15), P = 0.31], and duration of mechanical ventilation [MD = −0.93 days 95% CI (−2.90 to 1.04) P = 0.36] between the vitamin A and control group. Among the secondary outcomes, only the duration of CPAP/HFNC (days) showed statistically significant results [MD = −1.29, 95%CI (−1.93, −0.66), P < 0.0001]. Meanwhile, there was no statistically significant difference between the experimental and placebo groups with regards to duration of hospitalization, duration of minimally invasive ventilation and oxygen, requirement for postnatal steroids, serum retinol concentration at 28 days, necrotizing enterocolitis, periventricular leukomalacia, intraventricular hemorrhage and vomiting. Conclusion: Supplementing premature infants with enteral vitamin A might shorten the duration of noninvasive respiratory support requirement. However, there is a lack of evidence for its superior efficacy in improving the overall health outcomes for premature infants compared to placebo.

Objective: Peroxisome proliferator‐activated receptor (PPAR) agonists are agents used for patients with primary biliary cholangitis (PBC) who do not respond to conventional agents like ursodeoxycholic acid (UDCA). This meta‐analysis aimed to assess the safety and efficacy of PPAR agonists, including fibrates and selective PPAR agonists, on biochemical response and safety outcomes in patients with primary biliary cholangitis who were non‐responders to UDCA.Methods: We searched various electronic databases, including MEDLINE (via PubMed), Embase, the Cochrane Library, and ClinicalTrials.gov, to retrieve randomized controlled trials (RCTs) comparing PPAR agonists to placebo in patients with PBC.Results: Our meta‐analysis, including 12 RCTs involving 973 patients, showed that PPAR agonists, including fibrates and selective PPAR agonists, significantly reduce mean alkaline phosphatase (ALP) levels from baseline to follow‐up as compared to placebo. They also increase the number of patients with the composite biochemical response (RR 5.51; 95% CI: 2.80, 10.86) and normalize ALP levels with a reduction in pruritus NRS Score and the incidence of pruritus. There was no significant change between the two groups when assessing the mean change in total bilirubin, adverse events, serious adverse events, or mean change in PBC‐40 score.Conclusion: In conclusion, our research underscores the potential of novel PPAR agonists in improving biochemical markers in PBC, particularly in patients unresponsive to UDCA. However, further studies with larger sample sizes, longer follow‐up durations, and a focus on patient‐centered outcomes are necessary. Additionally, exploring combination therapies and mechanistic insights will help us fully realize the therapeutic potential of PPAR agonists in PBC.

Background : Tirofiban is a GP IIb/IIIa inhibitor, an anti‐platelet drug that is used in ischemic stroke or acute coronary syndromes. The goal of this study is to assess the safety and efficacy of the drug in patients who have suffered an acute ischemic stroke. Methods : A comprehensive search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to December 2025 yielded randomized controlled trials (RCTs) comparing Tirofiban and conventional management in patients with acute ischemic stroke. We assessed the risk of bias using the revised Cochrane “Risk of bias” tool for randomized trials (RoB 2.0). We analyzed the outcomes using RevMan 5.4, with risk ratio (RR) as the effect measure. Results : A total of 9 RCTs with 4210 patients were included in our meta‐analysis. According to our meta‐analysis, the tirofiban group was associated with a statistically significant increase in the patients showing functional independence at 90 days, measured by patients with Modified Rankin Score (mRS) of 0–2 (RR 1.13; CI = 1.06–1.20) and excellent outcome (mRS score 0–1) at 90 days (RR 1.17; CI = 1.05–1.29). We found no statistically significant difference between the two groups regarding mortality (RR 0.94; CI = 0.63–1.40). The tirofiban group had an increased incidence of intracranial hemorrhage (ICH) (RR 1.25; CI = 1.06–1.47) but had a similar incidence of symptomatic ICH as compared to the control group (RR 1.48; CI = 0.98–2.24). Conclusion : This meta‐analysis suggests that tirofiban may improve favorable functional outcomes (mRS 0–2) in acute ischemic stroke, although the certainty of evidence was moderate. While no significant increase in sICH was observed, some analyses showed a higher rate of overall intracranial hemorrhage. These findings should therefore be interpreted cautiously, and further high‐quality randomized trials are needed to confirm the efficacy and safety of tirofiban before routine guideline use.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder with no currently approved disease‐modifying treatments. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), originally used in type 2 diabetes, have demonstrated neuroprotective and anti‐inflammatory effects in preclinical PD models. This systematic review and meta‐analysis evaluated the efficacy and safety of GLP‐1RAs in patients with PD. Methods: A systematic search of MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov was conducted through July 2025 for randomized controlled trials (RCTs) comparing GLP‐1RAs to placebo in PD. Primary outcomes included MDS‐UPDRS Part III (motor examination) both on and off medication. Secondary outcomes included MDS‐UPDRS Parts I, II, IV, PDQ‐39, NMSS, and adverse effects. Data were pooled using a random‐effects model with results reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Results: Five RCTs involving 708 participants were included. No statistically significant differences were found in MDS‐UPDRS Part III scores off medication (MD: –2.00, 95% CI: –4.12 to 0.11, p = 0.06) or on medication (MD: –1.40, 95% CI: –3.42 to 0.62, p = 0.17). Secondary outcomes also showed no significant benefits with GLP‐1RA use. However, GLP‐1RAs were associated with increased gastrointestinal side effects, including nausea (RR: 2.09), vomiting (RR: 4.53), constipation (RR: 1.60), and weight loss (RR: 1.83). Conclusion: Current evidence does not demonstrate a statistically significant overall benefit of GLP‐1RAs on efficacy outcomes in PD, while gastrointestinal adverse events are increased. More trials are needed to clarify their disease‐modifying potential.