ABSTRACT
Background: The initial severity of acute ischemic stroke (AIS) is a crucial predictor of the disease outcome. In this study, blood and urine biomarkers from patients with AIS were measured to estimate stroke severity and predict long-term stroke outcomes. Methods: The medical records of patients with AIS between October 2016 and May 2020 were retrospectively analyzed. The relationships of blood and urine biomarkers with stroke severity at admission were evaluated in patients with AIS. Predictive models for initial stroke severity and long-term prognosis were then developed using a panel of identified biomarkers. Results: A total of 2229 patients were enrolled. Univariate analysis revealed 12 biomarkers associated with the National Institutes of Health Stroke Scale scores at admission. The area under the curve values for predicting initial stroke severity and long-term prognosis on the basis of these biomarkers were 0.7465, 0.7470, and 0.8061, respectively. Among multiple tested machine-learning, eXtreme gradient boosting exhibited the highest effectiveness in predicting 90-day modified Rankin Scale scores. SHapley Additive exPlanations revealed fasting glucose, albumin, hemoglobin, prothrombin time, and urine-specific gravity to be the top five most crucial biomarkers. Conclusion: These findings demonstrate that clinically available blood and urine biomarkers can effectively estimate initial stroke severity and predict long-term prognosis in patients with AIS. Our results provide a scientific basis for developing tailored clinical treatment and management strategies for AIS, through incorporating liquid biomarkers into stroke risk assessment and patient care protocols for patients with AIS.
ABSTRACT
Background: Metformin is a potent antiglycemic agent, but its importance has receded owing to the launch of novel antidiabetic medications. The benefit of metformin includes not only blood sugar control but also anti-inflammation, autophagy activation, and neuroprotection. This study investigated the risk of cardiovascular disease (CVD) in people with type II diabetes mellitus (T2DM) who adhered to metformin after adding on a second-line antiglycemic agent. Objectives: The purpose of this study was to investigate the benefits of metformin in CVD prevention in patients with T2DM. Design: We designed the study by comparing the incident rate of CVD events in patients with T2DM who received metformin continually and who ceased metformin during 2002-2014. Methods: Medical information was obtained from the National Health Insurance Research Database, and patients with T2DM receiving second-line antiglycemic agents were categorized into metformin-adherent and nonadherent groups according to prescription claims. The study outcomes were the incidence of CVD hospitalization, including stroke (ischemic and hemorrhagic) and myocardial infarction (MI). Results: A total of 31,384 patients with T2DM constituted the metformin-adherent group and were 1:1 matched to nonadherent patients. Metformin adherence was associated with a lower risk of hospitalization due to stroke [adjusted hazard ratio (aHR) = 0.51, 95% confidence interval (CI): 0.43-0.59, p < 0.001] and MI (aHR = 0.47, 95% CI: 0.43-0.53, p < 0.001). The risk reduction persisted in both ischemic and hemorrhagic strokes. Our subgroup analysis revealed that the protective effect on stroke and MI hospitalization persisted in metformin-adherent patients, both sexes, patients aged ⩽65 or >65 years, and patients with or without concurrent insulin treatment. Conclusions: This study revealed that metformin adherence in patients with T2DM who required a first-line treatment may reduce the risk of subsequent CVD. Despite the availability of numerous novel antiglycemic agents, metformin adherence by patients who require a combination of antiglycemic agents provides an additional benefit of CVD protection.
