Background: Alveolar bone reconstruction with recombinant protein has several advantages, including less surgical timing, and reduced infection. This systematic review aims to assess the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a treatment modality for children with cleft lip and palate compared to the conventional iliac crest bone grafting approach. Methods: For current systematic review and meta-analysis, five electronic databases, namely, MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Web of Science, and ScienceDirect, were searched. The primary outcome measured in this review was bone volume and height after alveolar bone reconstruction surgery. The Risk of Bias Tool 2 assessed the risk of bias for randomized control trials and the Risk of Bias tool for non-randomized trials of interventions for non-randomized studies. By evaluating pooled meta-analysis, the mean difference was calculated. GRADE uncertainty of evidence was performed to assess the certainty of the results. Results: Of 230 identified studies, 6 randomized and 2 non-randomized studies were included in the current review. The average bone volume was higher among the rhBMP-2 group at 61.11% ± 24.6% than the iliac crest group at 59.12% ± 18.59%. The calculated mean bone height was higher in the iliac crest group at 78.65% ± 14.38% than in the rhBMP-2 group at 67.5% ± 5.45%. The risk of bias reported in the studies was low to moderate. The result of the meta-analysis supported using rhBMP-2 in alveolar bone reconstruction; however, no significant association was found (mean difference: −1.24; confidence interval: −4.14 to 1.67). Conclusions: The calculated meta-analysis reported no significant difference, and the quality of evidence measured was also moderate. Hence, more clinical trials are required to support using rhBMP-2 as an alternative to traditional techniques for treating cleft lip and palate.
Purpose: Neurodegenerative and neurovascular disorders are increasingly recognized as major causes of disability worldwide and require accessible biomarkers for early detection and monitoring. Given the close anatomical and microvascular relationship between the retina and the central nervous system, optical coherence tomography angiography (OCTA) has emerged as a promising non-invasive technique for assessing retinal microvascular alterations associated with neurological disease. This systematic review and meta-analysis evaluated OCTA-derived retinal microvascular parameters as potential biomarkers of neurovascular dysfunction. Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420261305354). PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from January 2015 to December 2025. Studies comparing OCTA-derived retinal vascular parameters between patients with neurodegenerative or neurovascular disorders and healthy controls were included. Primary outcomes were superficial capillary plexus vessel density (SCP-VD), deep capillary plexus vessel density (DCP-VD), and foveal avascular zone (FAZ) area. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Results: Thirteen studies were included in the quantitative synthesis. Compared with healthy controls, patients with neurodegenerative or neurovascular disorders demonstrated significantly reduced SCP vessel density (SMD − 0.60, 95% CI − 0.78 to − 0.43; I2 = 43%) and DCP vessel density (SMD − 0.84, 95% CI − 1.15 to − 0.53; I2 = 78%). FAZ area was significantly enlarged in disease groups (SMD 0.62, 95% CI 0.29 to 0.94; I2 = 83%). Disease-specific subgroup analyses demonstrated generally consistent trends across the included disorders. Conclusion: OCTA-derived retinal microvascular alterations were consistently associated with neurodegenerative and neurovascular disorders. Reduced retinal vessel density, particularly within the deep capillary plexus, and enlargement of the FAZ may reflect underlying neurovascular dysfunction. While these findings support the potential role of OCTA as a non-invasive biomarker of neurological disease, the available evidence remains limited by methodological heterogeneity and predominantly observational study designs. Further longitudinal studies using standardized OCTA protocols are needed to establish the diagnostic and prognostic utility of these biomarkers.
17 December 2025 in Clinical and Experimental Obstetrics & Gynecology
Background: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), mainly used for non-small cell lung cancer. Because EGFR is also highly expressed in placental tissue, its use has been explored in the treatment of ectopic pregnancy. This review examines the available evidence on the safety and effectiveness of combining gefitinib with methotrexate for the treatment of ectopic pregnancy. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across PubMed, Web of Science, ProQuest, and Google Scholar for English-language studies published between 2013 and 2023 comparing gefitinib plus methotrexate to methotrexate alone. Study quality was assessed using Joanna Briggs Institute (JBI) tools for quasi-experimental studies and case reports. Meta-analysis was performed using OpenMeta-Analyst with a random-effects model at a 0.05 significance level and 95% confidence intervals (CI). Results: Of 162 identified studies, five met the inclusion criteria, and three were included in the meta-analysis, comprising 526 participants. The pooled analysis revealed no statistically significant difference in complete resolution rates between the combination therapy group (69.3%) and the methotrexate-alone group (75.5%) (relative risks (RR): 1.004, 95% CI: 0.802–1.257; p = 0.973; I2 = 63.96%). Adverse events were generally mild and self-limiting, with rash (60.8%) and diarrhea (46.5%) being the most common. Serious adverse events were rare (<4%) and occurred at similar rates in both groups. Conclusions: These findings suggest that while the combination of gefitinib and methotrexate is safe, it does not significantly enhance treatment outcomes compared to methotrexate alone in managing ectopic pregnancy. Registration: The study has been registered on https://www.crd.york.ac.uk/prospero/ (registration number: CRD42024500567; registration link: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024500567).