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Background: Hemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms of the underlying biomolecular mechanisms of its development. Circulating metabolites have been closely associated with HS in recent years. Therefore, we explored the causal association between circulating metabolomes and HS using Mendelian randomization (MR) analysis and identified the molecular mechanisms of effects. Methods: We assessed the causal relationship between circulating serum metabolites (CSMs) and HS using a bidirectional two-sample MR method supplemented with five ways: weighted median, MR Egger, simple mode, weighted mode, and MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO served for the sensitivity analyses. The Steiger test and reverse MR were used to estimate reverse causality. Metabolic pathway analyses were performed using MetaboAnalyst 5.0, and genetic effects were assessed by linkage disequilibrium score regression. Significant metabolites were further synthesized using meta-analysis, and we used multivariate MR to correct for common confounders. Results: We finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40-0.96, PMVMR = 0.030), linoleate (18. 2n6) (OR 0.20, 95% CI 0.08-0.54, PMVMR = 0.001),1-eicosadienoylglycerophosphocholine* (OR 2.21, 95% CI 1.02-4.76, PMVMR = 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) (OR 0.27, 95% CI 0.09-0.77, PMVMR = 0.015) with significant causal relation to HS. Conclusion: We demonstrated significant causal associations between circulating serum metabolites and hemorrhagic stroke. Monitoring, diagnosis, and treatment of hemorrhagic stroke by serum metabolites might be a valuable approach.
RESUMO
OBJECTIVE: Seizures are one of the complications that can occur after cranioplasty (CP). In some regions, titanium mesh remains the material of choice for CP. However, risk factors for seizures after titanium CP have been less studied. The purpose of this study was to identify potential risk factors for early seizures (≤7 days) and late seizures (>8 days) after titanium CP in a single institution. METHODS: A retrospective review was conducted of 241 consecutive patients who received titanium CP at the First Affiliated Hospital of Harbin Medical University from January 2016 to December 2020. Univariate and multivariable logistic regression analyses were performed to determine the independent risk factors for new-onset seizures after titanium CP. RESULTS: Fifteen patients (6.22%) experienced early post-CP seizures, and late post-CP seizures were observed in 81 patients (33.61%). A flaccid concave cranial defect (P = 0.042) was associated with early post-CP seizures, whereas hypertension (P < 0.001) was the only significant predictor for late seizures after titanium CP. CONCLUSIONS: Seizure is a common complication after titanium CP, especially in patients who do not receive prophylactic antiepileptic drugs before the procedure. Risk factors for new-onset seizures at different periods after titanium CP were found to be different. In addition, radiologic factors before titanium CP may play a role in early new-onset seizures after titanium CP and should not be ignored.