Predictive etiological classification of acute ischemic stroke through interpretable machine learning algorithms: a multicenter, prospective cohort study.

BACKGROUND: The prognosis, recurrence rates, and secondary prevention strategies varied significantly among different subtypes of acute ischemic stroke (AIS). Machine learning (ML) techniques can uncover intricate, non-linear relationships within medical data, enabling the identification of factors associated with etiological classification. However, there is currently a lack of research utilizing ML algorithms for predicting AIS etiology. OBJECTIVE: We aimed to use interpretable ML algorithms to develop AIS etiology prediction models, identify critical factors in etiology classification, and enhance existing clinical categorization. METHODS: This study involved patients with the Third China National Stroke Registry (CNSR-III). Nine models, which included Natural Gradient Boosting (NGBoost), Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Light Gradient Boosting Machine (LGBM), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting (AdaBoost), Support Vector Machine (SVM), and logistic regression (LR), were employed to predict large artery atherosclerosis (LAA), small vessel occlusion (SVO), and cardioembolism (CE) using an 80:20 randomly split training and test set. We designed an SFS-XGB with 10-fold cross-validation for feature selection. The primary evaluation metrics for the models included the area under the receiver operating characteristic curve (AUC) for discrimination and the Brier score (or calibration plots) for calibration. RESULTS: A total of 5,213 patients were included, comprising 2,471 (47.4%) with LAA, 2,153 (41.3%) with SVO, and 589 (11.3%) with CE. In both LAA and SVO models, the AUC values of the ML models were significantly higher than that of the LR model (P < 0.001). The optimal model for predicting SVO (AUC [RF model] = 0.932) outperformed the optimal LAA model (AUC [NGB model] = 0.917) and the optimal CE model (AUC [LGBM model] = 0.846). Each model displayed relatively satisfactory calibration. Further analysis showed that the optimal CE model could identify potential CE patients in the undetermined etiology (SUE) group, accounting for 1,900 out of 4,156 (45.7%). CONCLUSIONS: The ML algorithm effectively classified patients with LAA, SVO, and CE, demonstrating superior classification performance compared to the LR model. The optimal ML model can identify potential CE patients among SUE patients. These newly identified predictive factors may complement the existing etiological classification system, enabling clinicians to promptly categorize stroke patients' etiology and initiate optimal strategies for secondary prevention.

Glycated albumin levels are associated with adverse stroke outcomes in patients with acute ischemic stroke in China.

BACKGROUND AND AIM: Glycated albumin (GA) is a biomarker monitoring glycemia 2-4 weeks before stroke onset. This study was designed to explore the association between GA levels with poststroke outcomes in patients with acute ischemic stroke or transient ischemic attack (TIA). METHOD: Participants with ischemic stroke or TIA who had a baseline GA measurement were included in the Third China National Stroke Registry study. The effect of GA on stroke recurrence, poor functional outcomes, and combined vascular events was examined during the 1-year follow-up period. Multivariate Cox and logistic regression models were performed to evaluate the association. Discrimination tests were used to examine the incremental predictive value of GA when incorporating it into the conventional model. RESULTS: A total of 3861 participants were enrolled. At the 3-month follow-up, the elevated GA level was associated with an increased risk of poor functional outcomes (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.01-2.09). A similar increase was observed for stroke recurrence (adjusted hazard ratio [HR], 1.56; 95% CI, 1.09-2.24), poor functional outcomes (adjusted OR, 1.62; 95% CI, 1.07-2.45), and combined vascular events (adjusted HR, 1.55; 95% CI, 1.09-2.20) at the 1-year follow-up. In nondiabetic patients, the association between GA and poor functional outcomes was more pronounced (adjusted OR, 1.62; 95% CI, 1.05-2.50). Adding GA into the conventional model resulted in slight improvements in predicting poor functional outcomes (net reclassification improvement [NRI]: 12.30% at 1 year). CONCLUSION: This study demonstrated that elevated GA levels in serum were associated with stroke adverse outcomes, including stroke recurrence, poor functional outcomes, and combined vascular events, in patients with ischemic stroke or TIA.

Clinical characteristics, in-hospital management, and outcomes among patients hospitalized for acute ischemic stroke in rural vs. urban hospitals in China: a nationwide hospital-based study.

BACKGROUND: Efforts to improve rural stroke care have intensified in China. However, high-quality comprehensive data on the differences in care and outcomes between urban and rural hospitals are limited. METHODS: We analyzed data on patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals from 2015 to 2022. The in-hospital management measures assessed included nine acute and five discharge management measures. Outcomes evaluated included death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACE), disability at discharge, and in-hospital complications. RESULTS: We enrolled 1,583,271 patients with acute ischemic stroke from 1,930 hospitals, comprising 1 086 (56.3%) rural sites with 735 452 patients and 844 (43.7%) urban sites with 847 891 patients. Patients in rural hospitals demonstrate suboptimal management measures compared to those in urban hospitals, including lower rates of intravenous recombinant tissue plasminogen activator within 4.5 h (26.0% vs. 28.3%; difference, -2.3% [-2.5% to -2.0%]), endovascular treatment (0.6% vs. 1.9%; difference, -1.3% [-1.3% to -1.2%]), vessel assessment (88.5% vs. 92.0%; difference, -3.5% [95% CI, -3.6% to -3.4%]), and anticoagulants for atrial fibrillation at discharge (42.9% vs. 47.7%; difference, -4.8% [95% CI, -5.4% to -4.2%]). Overall, the rural-urban disparity in in-hospital outcomes was small. Rural patients had a slightly higher rate of in-hospital death/DAMA (9.0% vs. 8.0%; aOR, 1.22 [95% CI, 1.20-1.23]; aRD, 1.3% [95% CI, 1.2%-1.4%]) and a slightly lower rate of complications (10.9% vs. 13.0%; aOR, 0.83 [95% CI, 0.82-0.84]; aRD, -1.3% [95% CI, -1.3%-1.3%]). No notable rural-urban differences were observed in MACE and disability at discharge. CONCLUSIONS: Patients in rural hospitals demonstrated suboptimal management measures and had higher rates of in-hospital death/DAMA compared to those in urban hospitals. Prioritizing the allocation of health resources to rural hospitals is essential to improve healthcare quality and outcomes. DATA ACCESS STATEMENT: The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Association between PPARγ polymorphisms and neurological functional disability of ischemic stroke.

Peroxisome proliferator-activated receptor-γ (PPARγ) plays a protective role against brain injury after stroke in mice. However, the relationship between PPARγ gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in PPARγ, rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, Pinteraction = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.

DNMT3A dysfunction promotes neuroinflammation and exacerbates acute ischemic stroke.

Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well-characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A-driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.

Non-O blood types are associated with a greater risk of large artery atherosclerosis stroke and dysregulation of cholesterol metabolism: an observational study.

BACKGROUND: Previous research on ABO blood types and stroke has been controversial, predominantly suggesting heightened risk of stroke in non-O blood types. Nonetheless, investigations into the correlation and underlying mechanisms between ABO blood groups and stroke subtypes, especially within Chinese cohorts, remain limited. METHODS: The ABO blood types of 9,542 ischaemic stroke (IS) patients were inferred using two ABO gene loci (c.261G > del; c.802G > A). The healthy population was derived from the 1000 Genomes Project. Patients were classified by the causative classification system (CCS). Volcano plot and gene ontology (GO) analysis were employed to explore protein differential expression among blood types. Additionally, HT29 and SW480 cell lines with downregulated ABO expression were generated to evaluate its impact on cholesterol uptake and efflux. RESULTS: A greater proportion of stroke patients had non-O blood types (70.46%) than did healthy individuals (61.54%). Notable differences in blood type distributions were observed among stroke subtypes, with non-O blood type patients mainly classified as having large artery atherosclerosis (LAA). Clinical baseline characteristics, such as the low-density lipoprotein cholesterol level, activated partial thromboplastin time and thrombin time, varied significantly among blood types. A volcano plot revealed 17 upregulated and 42 downregulated proteins in the O blood type. GO term analysis indicated that downregulated proteins were primarily associated with lipid metabolism pathways. In vitro experiments revealed that reducing ABO gene expression decreased cholesterol uptake and increased cholesterol efflux. CONCLUSIONS: This study revealed that the non-O blood type increased the risk of LAA stroke through cholesterol metabolism.

Reteplase versus Alteplase for Acute Ischemic Stroke.

BACKGROUND: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear. METHODS: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset. RESULTS: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20). CONCLUSIONS: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.).

RhPro-UK in acute ischemic stroke within 4.5 h of stroke onset trial-2 (the PROST-2 study): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial.

BACKGROUND: Recombinant prourokinase (rhPro-UK) is a specific plasmin activator, which has been approved to treat acute myocardial infarction in China. AIM: This phase 3 trial aimed to further demonstrate the efficacy and safety of rhPro-UK in patients with acute ischemic stroke (AIS) within 4.5 h of symptom onset. METHODS AND DESIGN: RhPro-UK in AIS within 4.5 h of stroke onset trial-2 (PROST-2) is a multicenter, prospective randomized, open-label, blinded end-point, non-inferiority, recombinant tissue plasmin activator (rt-PA)-controlled, phase 3 trial. A total of 1552 patients who are eligible for intravenous thrombolytic therapy from 72 clinical sites will be randomly assigned to receive either rhPro-UK 35 mg (15 mg bolus + 20 mg infusion/30 min) or rt-PA 0.9 mg/kg (10% bolus + 90% infusion/1 h). STUDY OUTCOMES: The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary efficacy outcomes include the proportion of patients with mRS score of 0-2, the distribution of mRS, self-care ability in daily life on the Barthel Index at 90 days, the proportion of subjects with ⩾ 4 points decrease in National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score ⩽ 1 from baseline at 24 h and 7 days after treatment. Safety outcomes are symptomatic intracranial hemorrhage (sICH) and major systematic bleeding within 7 days as well as death from all causes within 90 days. DISCUSSION: The results from the PROST-2 trial will comprehensively elucidate the efficacy and safety profile of rhPro-UK as a potential alternative agent for stroke thrombolysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591.

Data-Driven Analysis Reveals Cortical Infarction Patterns Correlated With Inflammation and Prognosis: A Retrospective, Multicenter Cohort Study.

BACKGROUND: We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. METHODS AND RESULTS: We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. CONCLUSIONS: Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.

Thrombocytopenia and In-hospital outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis: Findings from a nationwide registry study in China.

BACKGROUND AND OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02). CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.

Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.

OBJECTIVES: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN: Multicentre, double blind, randomised, placebo controlled trial. SETTING: 244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). CONCLUSIONS: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05439356.

Hemodynamic Impairment of Blood Pressure and Stroke Mechanisms in Symptomatic Intracranial Atherosclerotic Stenosis.

BACKGROUND: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment. METHODS: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018. The major exposures were translesional systolic blood pressure (SBP) drop and poststenotic mean arterial pressure (MAP), and the major study outcomes were cortex-involved infarcts and borderzone-involved infarcts, respectively. Multivariate logistic regression models and the bootstrap resampling method were utilized, adjusting for demographics and medical histories. RESULTS: In all, 184 (54.3%) cortex-involved infarcts and 70 (20.6%) borderzone-involved infarcts were identified. In multivariate logistic model, the upper quartile of SBP drop correlated with increased cortex-involved infarcts (odds ratio, 1.92 [95% CI, 1.03-3.57]; bootstrap analysis odds ratio, 2.07 [95% CI, 1.09-3.93]), and the lower quartile of poststenotic MAP may correlate with increased borderzone-involved infarcts (odds ratio, 2.07 [95% CI, 0.95-4.51]; bootstrap analysis odds ratio, 2.38 [95% CI, 1.04-5.45]). Restricted cubic spline analysis revealed a consistent upward trajectory of the relationship between translesional SBP drop and cortex-involved infarcts, while a downward trajectory between poststenotic MAP and borderzone-involved infarcts. SBP drop correlated with poststenotic MAP negatively (rs=-0.765; P<0.001). In generating hemodynamic impairment, simulating blood pressure modifications suggested that ensuring adequate blood pressure to maintain sufficient poststenotic MAP appears preferable to the reverse approach, due to the prolonged plateau period in the association between the translesional SBP drop and cortex-involved infarcts and the relatively short plateau period characterizing the correlation between poststenotic MAP and borderzone-involved infarcts. CONCLUSIONS: This research elucidates the role of hemodynamic impairment of blood pressure in symptomatic intracranial atherosclerotic stenosis-related stroke mechanisms, underscoring the necessity to conduct hemodynamic assessments when managing blood pressure in symptomatic intracranial atherosclerotic stenosis.

The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Comparison of stress hyperglycemia ratio and glycemic gap on acute ICH in-hospital outcomes.

OBJECTIVE: To compare the effect of different indicators on stress-induced hyperglycemia for predicting in-hospital outcomes of acute intracerebral hemorrhage. METHODS: Using data from the Chinese Stroke Center Alliance database, which is a national, multicenter, prospective, and consecutive program. Stress-induced hyperglycemia was described as glycemic gap (GG, defined as fasting blood glucose [FBG] minus estimated average blood glucose) and stress hyperglycemia ratio (SHR, defined as FBG-to-estimated average blood glucose ratio [SHR 1] or FBG-to-HbA1c ratio [SHR 2]). The primary outcome was in-hospital mortality, and the second outcome was hematoma expansion. RESULTS: A total of 71,333 patients with acute intracerebral hemorrhage were included. In multivariate analyses, the highest levels of GG (OR 1.68, 95% CI 1.12-2.51), SHR 1 (OR 1.73, 95% CI 1.15-2.60), and SHR 2 (OR 2.07, 95% CI 1.33-3.23) were associated with in-hospital death (all the p trends <0.01). Only the highest level of SHR 2 (OR 1.24 [1.02-1.51], p trend >0.05) was related to hematoma expansion. No association between GG or SHR 1 and hematoma expansion was observed. The areas under the ROC curve of GG, SHR 1, and SHR 2 for in-hospital mortality were 0.8808 (95% CI 0.8603-0.9014), 0.8796 (95% CI 0.8589-0.9002), and 0.8806 (95% CI 0.8600-0.9012). The areas under the ROC curve of SHR 2 for hematoma expansion were 0.7133 (95% CI 0.6964-0.7302). INTERPRETATION: SHR (FBG-to-HbA1c ratio) was associated with both in-hospital death and hematoma expansion in intracerebral hemorrhage, and might serve as an accessory indicator for the in-hospital prognosis of intracerebral hemorrhage.

Gait speed at the acute phase predicted health-related quality of life at 3 and 12 months after stroke: a prospective cohort study.

OBJECTIVE: To investigate the association between acute-phase gait speed and health-related quality of life (HRQoL) at 3 and 12 months post-stroke. DESIGN: Prospective cohort study. SUBJECTS/PATIENTS: 1,475 patients with first-ever ischaemic stroke. METHODS: The patients were divided into 3 groups according to tertiles of gait speed, namely ≤0.8, 0.8-1.1, ≥1.1 m/s. Gait speed was assessed by the 10-m walking test within 2 weeks of hospitalization for acute stroke and before the rehabilitation programme. HRQoL measurements include the 3-level EuroQol five dimensions (EQ-5D-3L) index and EuroQoL visual analogue scale (EQ-VAS) scores. Linear and logistic regression analyses were used to identify associations between gait speed and HRQoL. RESULTS: Adjusted for all covariates, the highest gait speed tertile group were associated with higher EQ-5D-3L index (B = 0.0303 and B = 0.0228, respectively, p < 0.001), and higher EQ-VAS (B = 3.3038 and B = 3.8877, respectively, p < 0.001), and lower odds of having problems with mobility (OR = 2.55 [95% CI: 0.141-0.458] and 0.485 [0.289-0.812], respectively, p < 0.01), self-care (OR = 0.328 [95% CI: 0.167-0.646] and 0.412 [0.217-0.784], respectively, p < 0.01), and usual activities (OR = 0.353 [95% CI: 0.211-0.590] and 0.325 [0.198-0.536], respectively, p < 0.0001) at 3 and 12 months, and pain/discomfort at 12 months (OR = 0.558 [95% CI:0.335-0.930], p < 0.05). CONCLUSION: Acute-phase gait speed was predictive of post-stroke HRQoL at 3 and 12 months, especially when associated with domain-specific EQ-5D-3L.

Impact of Off-Hour Admission on In-Hospital Outcomes for Patients With Stroke Receiving Reperfusion Therapy in China.

BACKGROUND: The structure and staffing of hospitals greatly impact patient outcomes, with frequent changes occurring during nights and weekends. This retrospective cohort study assessed the impact of admission timing on in-hospital management and outcomes for patients with stroke receiving reperfusion therapy in China using data from a nationwide registry. METHODS: Data from patients receiving reperfusion therapy were extracted from the Chinese Stroke Center Alliance. Hospital admission time was categorized according to day/evening versus night and weekday versus weekend. Primary outcomes were in-hospital death or discharge against medical advice, hemorrhage transformation, early neurological deterioration, and major adverse cardiovascular events. Logistic regression was performed to compare in-hospital management performance and outcomes based on admission time categories. RESULTS: Overall, 42 381 patients received recombinant tissue-type plasminogen activator (r-tPA) therapy, and 5224 underwent endovascular treatment (EVT). Patients admitted during nighttime had a higher probability of receiving r-tPA therapy within 4.5 hours from onset or undergoing EVT within 6 hours from onset compared with those admitted during day/evening hours (adjusted odds ratio, 1.04 [95% CI, 1.01-1.08]; P=0.021; adjusted odds ratio, 1.72 [95% CI, 1.59-1.86]; P<0.001, respectively). However, no significant difference was observed between weekend and weekday admissions for either treatment. No notable differences were noted between weekends and weekdays or nighttime and daytime periods in door-to-needle time for r-tPA or door-to-puncture time for EVT initiation. Furthermore, weekend or nighttime admission did not have a significant effect on the primary outcomes of r-tPA therapy or EVT. Nevertheless, in patients undergoing EVT, a higher incidence of pneumonia was observed among those admitted at night compared with those admitted during day/evening hours (adjusted odds ratio, 1.22 [95% CI, 1.05-1.42]; P=0.011). CONCLUSIONS: Patients admitted at nighttime were more likely to receive r-tPA therapy or EVT within the time window recommended in the guidelines. However, patients receiving EVT admitted at night had an increased risk of pneumonia.

Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

AIM: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. METHODS: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

Rationale and design of Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol II (TASTE-2): a multicentre randomised controlled trial.

BACKGROUND: Edaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol (TASTE) trial demonstrated its superior efficacy over edaravone alone for acute ischaemic stroke (AIS) patients. However, its efficacy in individuals undergoing endovascular therapy (EVT) remains uncertain. AIM: To clarify the rationale and design of the TASTE II (TASTE-2) trial. DESIGN: The TASTE-2 is a multicentre, double-blind, randomised, placebo-controlled trial designed to evaluate the efficacy and safety of edaravone dexborneol in patients with AIS and large-vessel occlusion in the anterior circulation. The eligible participants, presenting with a National Institute of Health Stroke Scale score between 6 and 25 (range 0-42, with larger values suggesting severe neurological dysfunction) and an Alberta Stroke Program Early Computed Tomography Score ranging from 6 to 10 (range 0-10, with smaller values suggesting larger infarction) within the initial 24 hours after symptom onset, will be randomly allocated to either the edaravone dexborneol group or the placebo group in equal proportions prior to thrombectomy. The treatment will be continuously administered for a duration of 10-14 days. A follow-up period of 90 days will be implemented for all participants. STUDY OUTCOMES: The primary efficacy outcome is defined as achieving favourable functional independence, measured by a modified Rankin Scale of 0-2 at 90 days. The primary safety outcome focuses on the incidence of serious adverse events. DISCUSSION: The TASTE-2 trial will provide evidence to determine whether the administration of edaravone dexborneol in AIS patients undergoing EVT could yield significant improvements in neurological function.

Assessment of rehabilitation following acute ischaemic stroke in China: a registry-based retrospective observational study.

OBJECTIVES: This study aimed to describe the frequency, determinants and outcomes for assessment of patients who had an acute ischaemic stroke (AIS) for rehabilitation during hospitalisation in China. DESIGN: A registry-based retrospective observational study. STUDY DESIGN AND SETTINGS: Data regarding assessment or rehabilitation were extracted from the Chinese Stroke Center Alliance database from 1 August 2015 to 31 July 2019. Univariate and multivariate analyses were conducted to identify patient and hospital characteristics associated with rehabilitation assessment during acute hospitalisation as well as discharge outcomes. STUDY COHORT: We included 837 897 patients who had a stroke in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital designation. PRIMARY AND SECONDARY OUTCOME MEASURES: Rehabilitation assessment and discharge outcomes. RESULTS: Among 837 897 patients who had a stroke admitted to 1473 hospitals, 615 991 (73.5%) underwent rehabilitation assessment. There were significant variations in the rates of rehabilitation assessment across hospitals (IQR 61.3% vs 92.9%). According to multivariate analysis, guideline recommended care delivery was associated with a higher rehabilitation assessment rate, whereas high/low body mass index, ambulation (OR 0.88; 95% CI 0.87 to 0.90), history of stroke (OR 0.94; 95% CI 0.93 to 0.95), coronary heart disease (OR 0.84; 95% CI 0.82 to 0.85) and atrial fibrillation (OR 0.91; 95% CI 0.89 to 0.94) were associated with a lower rate. Additionally, rehabilitation assessment during hospitalisation was significantly associated with lower in-hospital mortality (OR 0.38; 95% CI 0.35 to 0.41) and a higher probability of discharge to a rehabilitation centre (OR 2.66; 95% CI 2.5 to 2.82). CONCLUSIONS: Nearly one-quarter of patients who had an AIS do not undergo documented rehabilitation assessment and compliance across hospitals varies. Thus, it is necessary to improve adherence to rehabilitation assessment to improve the quality of medical care for patients who had an AIS.

Implementation of early prophylaxis for deep-vein thrombosis in intracerebral hemorrhage patients: an observational study from the Chinese Stroke Center Alliance.

BACKGROUND: There is substantial evidence to support the use of several methods for preventing deep-vein thrombosis (DVT) following intracerebral hemorrhage (ICH). However, the extent to which these measures are implemented in clinical practice and the factors influencing patients' receipt of preventive measures remain unclear. Therefore, we aimed to evaluate the rate of the early implementation of DVT prophylaxis and the factors associated with its success in patients with ICH. METHODS: This study enrolled 49,950 patients with spontaneous ICH from the Chinese Stroke Center Alliance (CSCA) between August 2015 and July 2019. Early DVT prophylaxis implementation was defined as an intervention occurring within 48 h after admission. Univariate and multivariate logistic regression analyses were conducted to identify the rate and factors associated with the implementation of early prophylaxis for DVT in patients with ICH. RESULTS: Among the 49,950 ICH patients, the rate of early DVT prophylaxis implementation was 49.9%, the rate of early mobilization implementation was 29.49%, and that of pharmacological prophylaxis was 2.02%. Factors associated with an increased likelihood of early DVT prophylaxis being administered in the multivariable model included receiving early rehabilitation therapy (odds ratio [OR], 2.531); admission to stroke unit (OR 2.231); admission to intensive care unit (OR 1.975); being located in central (OR 1.879) or eastern regions (OR 1.529); having a history of chronic obstructive pulmonary disease (OR 1.292), ischemic stroke (OR 1.245), coronary heart disease or myocardial infarction (OR 1.2); taking antihypertensive drugs (OR 1.136); and having a higher Glasgow Coma Scale (GCS) score (OR 1.045). Conversely, being male (OR 0.936), being hospitalized in tertiary hospitals (OR 0.778), and having a previous intracranial hemorrhage (OR 0.733) were associated with a lower likelihood of early DVT prophylaxis being administered in patients with ICH. CONCLUSIONS: The implementation rate of early DVT prophylaxis among Chinese patients with ICH was subpar, with pharmacological prophylaxis showing the lowest prevalence. Various controllable factors exerted an impact on the implementation of early DVT prophylaxis in this population.