This meta-analysis of observational studies suggests that current use of OCs could contribute to a small increased risk of hemorrhagic stroke, and the increased risk is related to subarachnoid hemorrhage, but not intracerebral hemorrhage.

Background circular RNAs (circRNAs) are expressed abundantly in the brain and are implicated in the pathophysiology of neuropsychiatric disease. However, the potential clinical value of circRNAs in major depressive disorder (MDD) remains unclear. Methods RNA sequencing was conducted in whole-blood samples in a discovery set (7 highly homogeneous MDD patients and 7 matched healthy controls [HCs]). The differential expression of circRNAs was verified in an independent validation set. The interventional study was conducted to assess the potential effect of the antidepressive treatment on the circRNA expression. Findings in the validation set, compared with 52 HCs, significantly decreased circFKBP8 levels (Diff: -0.24; [95% CI -0.39 ~ -0.09]) and significantly elevated circMBNL1 levels (Diff: 0.37; [95% CI 0.09 ~ 0.64]) were observed in 53 MDD patients. The expression of circMBNL1 was negatively correlated with 24-item Hamilton Depression Scale (HAMD-24) scores in 53 MDD patients. A mediation model indicated that circMBNL1 affected HAMD-24 scores through a mediator, serum brain-derived neurotrophic factor. In 53 MDD patients, the amplitude of low-frequency fluctuations in the right orbital part middle frontal gyrus was positively correlated with circFKBP8 and circMBNL1 expression. Furthermore, the interventional study of 53 MDD patients demonstrated that antidepressive treatment partly increased circFKBP8 expression and the change in expression of circFKBP8 was predictive of further reduced HAMD-24 scores. Interpretation whole-blood circFKBP8 and circMBNL1 may be potential biomarkers for the diagnosis of MDD, respectively, and circFKBP8 may show great potential for the antidepressive treatment.

Background: Poly (ADP-ribose) polymerase (PARP) inhibitors, which are among the most important breakthroughs in precision medicine, have played a crucial role in cancer treatment. Understanding the toxicity profiles of the different PARP inhibitors will improve strategic treatment in clinical practice. Methods: PubMed, Cochrane Library, and Web of Science were systematically searched to include related studies published in English between January 2009 and February 2020. Only prospective, phase II and III randomized controlled trials were included. The following treatment groups were analyzed: niraparib, talazoparib, olaparib, rucaparib, conventional therapy (chemotherapy), one PARP inhibitor with one angiogenesis inhibitor, and placebo. Baseline data and adverse event data were extracted from the Bayesian random-effects network meta-analysis.Results: Fourteen phase II and III randomized controlled trials (4,336 patients) were included. When considering grade 3-5 adverse events, olaparib may be a better choice (probability =57%), followed by conventional therapy (50%), talazoparib (45%), rucaparib (75%), niraparib (77%), and a PARP inhibitor with one angiogenesis inhibitor (94%). Niraparib and rucaparib had higher risks for hematological and gastrointestinal toxicities, respectively. Talazoparib was safer for gastrointestinal function. Constipation and neutropenia were less observed in olaparib, but the risks for anorexia increased. The combination of PARP inhibitor and angiogenesis inhibitor increased the risk of general, metabolic, and gastrointestinal disorders.Conclusions: This network meta-analysis suggested that the toxicity spectrum of each PARP inhibitor is different. Olaparib had the best safety profile among all PARP inhibitors because of its mild toxicity and narrow spectrum. This study may guide clinicians and support further research.

BackgroundThis meta-analysis was designed to explore the relationship between the level of serum potassium and the treatment effect of epidermal growth factor receptor (EGFR) antagonist in advanced non-small cell lung cancer (aNSCLC).MethodsWe searched phase II/III prospective clinical trials on treatment with EGFR antagonists for aNSCLC patients. The objective response rate (ORR) and/or the disease control rate (DCR) and the incidence of hypokalemia of high grade (equal to or greater than grade 3) were summarized from all eligible trials. Heterogeneity, which was evaluated by Cochran’s Q-test and the I2 statistics, was used to determine whether a random effects model or a fixed effects model will be used to calculate pooled proportions. Subgroup analysis was performed on different interventions, line types, phases, and drug numbers.ResultsFrom 666 potentially relevant articles, 36 clinical trials with a total of 9,761 participants were included in this meta-analysis. The pooled ORR was 16.25% (95%CI = 12.45–21.19) when the incidence of hypokalemia was 0%–5%, and it increased to 34.58% (95%CI = 24.09–45.07) when the incidence of hypokalemia was greater than 5%. The pooled DCR were 56.03% (95%CI = 45.03–67.03) and 64.38% (95%CI = 48.60–80.17) when the incidence rates of hypokalemia were 0%–5% and greater than 5%, respectively. The results of the subgroup analysis were consistent with the results of the whole population, except for not first-line treatment, which may have been confounded by malnutrition or poor quality of life in long-term survival.ConclusionThe efficacy of anti-EGFR targeted therapy was positively associated with the hypokalemia incidence rate. Treatment effects on the different serum potassium strata need to be considered in future clinical trials with targeted therapy.

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