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Stroke recurrence significantly improves the prognosis quoad vitam et valetudinem of patients with a first ischemic or haemorrhagic stroke. Other than in bone and skeletal metabolism, vitamin D is involved in the pathogenesis of cardiovascular disorders. This meta-analysis was performed to evaluate the relationship between 25OH-vitamin D [25(OH)D] levels at the first stroke and the stroke recurrence. To 31 July 2022, four prospective studies were identified. The potential non-linear relationship was evaluated by modelling 25(OH)D, using restricted cubic splines of 25(OH)D distribution. The pooled estimated risk (and 95% CI) of the recurrence of stroke, comparing the highest and the lowest levels, was assessed using a random-effect model. A non-linear association was found by dose-response analysis. This study found that 25(OH)D levels at the first stroke ≥9.3 ng/mL were associated with a lower risk of stroke recurrence, compared with 25(OH)D levels ≤8.5 ng/mL. In the pooled analysis, higher 25(OH)D levels at the first stroke significantly reduce the risk of stroke recurrence, with a significant heterogeneity among studies. In conclusion, 25(OH)D levels ≤8.5 ng/mL at the first stroke are significantly associated with a higher risk of recurrent stroke.

Effective predictive biomarkers are needed for checkpoint inhibitors (ICI) based-immunotherapy in non-small-cell lung cancer (NSCLC). This study aims to evaluate whether single nucleotide polymorphisms (SNPs) in programmed cell death-ligand 1 (PD-L1) might effectively predict tumor response to ICI in Caucasian patients with advanced NSCLC. Peripheral blood samples and clinico-pathological data were prospectively collected from advanced NSCLC patients treated with anti-Programmed cell death protein 1 (PD-1) inhibitor nivolumab. rs822336, rs2282055 and rs4143815 PD-L1 SNPs were analysed based on previous reports available in the literature. PD-L1 SNPs were analysed following DNA extraction from stored peripheral blood lymphocytes by Taqman Real-Time PCR assay. Presence of PD-L1 SNPs were correlated with clinico-pathological data. Mechanisms underlying the effect of PD-L1 SNPs on PD-L1 expression were analysed in vitro utilizing five NSCLC cell lines, RNA expression and flow cytometry analysis as well as PROMO bioinformatic tool. PD-L1 SNPs localization were analysed utilizing Ensembl genome browser. Differences were considered statistically significant with p value< 0.05. Twenty-eight patients were included in the study. rs2282055 was present as wild type (wt) TT (rs2282055>T), GT and GG genotype in 56.25%, 34.38% and 9.38%, respectively, of patients. On the other hand, rs822336 was present as wt GG (rs822336>G), GC and CC genotype in 28.13%, 37.50% and 34.38%, respectively, of patients. Progression free survival (PFS) was significantly correlated with presence of both PD-L1 SNPs rs2282055 and rs822336 but not with rs4143815. Patients carrying GG either for rs2282055 or rs822336 had a significantly (p=0.0434 and p=0.0131, respectively) shorter PFS as compared to those carrying other PD-L1 SNP genotypes. NSCLC cell lines carrying either GG for rs2282055 or rs822336 significantly (p Citation Format: Francesco Sabbatino, Giovanna Polcaro, Luigi Liguori, Valentina Manzo, Valeria Conti, Jessica Dal Col, Anita Vergatti, Cristiana Stellato, Vincenzo Casolaro, Amelia Filippelli, Soldano Ferrone, Stefano Pepe. Single nucleotide polymorphisms (SNPs) in PD-L1 as predictive biomarkers for checkpoint inhibitor based-immunotherapy in caucasian patients with advanced NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3132.