Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe neurological event with limited treatment options, and little is known about its pathophysiology. There are few objective tools for predicting outcomes of aSAH patients and further aiding in directing clinical therapeutic programs. This study aimed to determine whether an elevated serum D-dimer/albumin ratio (DAR) reflects disease severity and predicts aSAH outcomes. Methods: We included 178 patients with aSAH. Data included demographics; clinical severity of aSAH (World Federation of Neurological Societies (WFNS) grade and Hunt–Hess grade); levels of D-dimer, albumin, and c-reactive protein (CRP); leukocyte counts on admission; and three-month outcomes. The outcomes were dichotomized into good and poor. The predictive ability of DAR for outcomes was determined using receiver operating characteristic (ROC) curve analysis. Results: Serum DAR showed a positive correlation with disease severity. Univariate analysis revealed that DAR, WFNS grade, Hunt–Hess grade, delayed cerebral infarction (DCI), age, neutrophil-to-lymphocyte ratio (NLR), and CRP/albumin ratio (CAR) were associated with unfavorable outcomes. Multivariate regression analysis further revealed that elevated DAR predicted poor outcomes after adjusting for WFNS grade, Hunt–Hess grade, DCI, age, NLR, and CRP/albumin ratio. Receiver operating characteristic curve analysis revealed that DAR predicted outcomes at a level comparable with NLR and CAR and had superior predictivity than D-dimer alone. Conclusion: DAR is a promising objective tool for aSAH outcome prediction. A high content DAR was associated with disease severity and unfavorable short-term outcomes.
The diagnosis and clinical management of aneurysmal subarachnoid hemorrhage (aSAH) is currently limited by the lack of accessible molecular biomarkers that reflect the pathophysiology of disease. We used microRNAs (miRNAs) as diagnostics to characterize plasma extracellular vesicles in aSAH. It is unclear whether they can diagnose and manage aSAH. Next-generation sequencing (NGS) was used to detect the miRNA profile of plasma extracellular vesicles (exosomes) in three patients with SAH and three healthy controls (HCs). We identified four differentially expressed miRNAs and validated the results using quantitative real-time polymerase chain reaction (RT-qPCR) with 113 aSAH patients, 40 HCs, 20 SAH model mice, and 20 sham mice. Exosomal miRNA NGS revealed that six circulating exosomal miRNAs were differentially expressed in patients with aSAH versus HCs and that the levels of four miRNAs (miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p) were differentially significant. After multivariate logistic regression analysis, only miR-369-3p, miR-486-3p, and miR-193b-3p enabled prediction of neurological outcomes. In a mouse model of SAH, greater expression of miR-193b-3p and miR-486-3p remained statistically significant relative to controls, whereas expression levels of miR-369-3p and miR-410-3p were lower. miRNA gene target prediction showed six genes associated with all four of these differentially expressed miRNAs. The circulating exosomes miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p may influence intercellular communication and have potential clinical utility as prognostic biomarkers for aSAH patients.
This study is an initial step to validate the objective existence of Lung and Large Intestine exterior-interior relationship intermediate structures, as described in the Chinese classical medical literatures, through the functional imaging angle. The intermediate structures are the pathological reaction areas of the bronchial asthmatic patients.
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