Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs.Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence.Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC), colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis), endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency), digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin), respiratory system (pneumonitis, lung infiltration, and interstitial lung disease), and urinary system (increased creatinine, nephritis, and renal failure). In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73–32.61; I2, 92.80) in any grade and 6.10% (95% CI, 4.85–7.64; I2, 52.00) in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%.Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.

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Background and purpose: Stroke is a leading cause of death and acquired disability in adults today. Inflammation plays an important role in the pathophysiology of stroke. The peripheral neutrophil-to-lymphocyte ratio (NLR) is an important global inflammatory indicator becoming more mainstream in stroke care. This meta-analysis aims to evaluate the relationship between the baseline NLR and acute ischemic and hemorrhagic stroke, as well as define the clinical significance of NLR in subtypes of ischemic stroke.Methods: This meta-analysis was registered in PROSPERO with the number CRD42018105305. We went through relevant articles from PubMed Central (PMC) and EMBASE. Prospective and retrospective studies were included if related to baseline NLR levels prior to treatment in patients with ischemic or hemorrhagic stroke. Studies were identified up until April 2019. The cutoff value for NLR and the sources of odds ratios (ORs)/risk ratios (RRs) were measured. Modified Rankin Scale (mRS) was used to investigate the outcomes during clinical follow-up. Predefined criteria were used to evaluate the risk of bias in eligible studies. P-values < 0.05 were considered statistically significant. STATA version 14.0 (STATA, College Station, TX) was used in all statistical analyses.Results: Thirty-seven studies with 43,979 individuals were included in the final analysis. Higher NLR levels were correlated with increased risk of ischemic stroke (ORs/RRs = 1.609; 95% CI = 1.283–2.019), unfavorable functional outcome at 3 months (ORs/RRs = 1.851; 95% CI = 1.325–2.584), and increased mortality in patients with ischemic stroke (ORs/RRs = 1.068; 95% CI = 1.027–1.111). While in terms of hemorrhagic stroke (including SAH and ICH), elevated NLR levels only had deleterious effects on mortality (ORs/RRs = 1.080; 95% CI = 1.018–1.146).Conclusions: Baseline NLR level is a promising predictor of the clinical outcomes in both ischemic and hemorrhagic stroke. In addition, elevated NLR is also associated with a high risk of ischemic stroke occurrence. However, future studies are needed to demonstrate the underlying mechanisms and further explain this association.

Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor progression, mainly through immune suppression. Inverse correlations have been observed between MDSC levels and patient survival for various malignancies. The purpose of this meta-analysis was to evaluate the prognostic value of pretreatment circulating MDSCs. We searched MEDLINE and EMBASE from their inceptions to September 2017 to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) were estimated for overall survival (OS) and combined disease-free survival, progression-free survival, and recurrence-free survival (DFS/PFS/RFS). A total of 40 studies comprising 2721 were included. For solid tumors, high levels of pretreatment circulating MDSCs were significantly associated with worse OS (HR = 1.796, 95% CI = 1.587-2.032) and DFS/PFS/RFS (HR = 2.459, 95% CI = 2.018-2.997). Breast cancer showed the largest association between high MDSC levels and worse OS (pooled HR = 3.053). Elevated MDSCs were also associated with worse OS for mixed-stage tumors (pooled HR = 1.659) and advanced-stage tumors (pooled HR = 2.337). Furthermore, both monocytic-MDSCs (M-MDSCs) and granulocytic or polymorphonuclear (PMN-MDSCs) showed negative associations with survival outcomes. Overall, high levels of pretreatment circulating MDSCs negatively influenced survival in most cancers. Pretreatment circulating MDSCs should be taken into account to further improve prognostic evaluation and develop novel therapeutic strategies.