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Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen–glucose deprivation/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen–glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

Acute ischemic stroke is a clinical emergency and a condition with high morbidity, mortality, and disability. Accurate predictive, diagnostic, and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined. With innovations in high-throughput gene sequencing analysis, many aberrantly expressed non-coding RNAs (ncRNAs) in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models. Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes, leading to neuroprotection or deterioration, thus ncRNAs can serve as therapeutic targets in acute ischemic stroke. Moreover, distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. In particular, ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke. In this review, we consolidate the latest progress of research into the roles of ncRNAs (microRNAs, long ncRNAs, and circular RNAs) in the pathological processes of acute ischemic stroke–induced brain damage, as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Background and purposeThe baseline glucose-to-potassium ratio (GPR) is associated with poor outcomes in patients with acute brain injury and intracranial hemorrhage. However, the impact of serum GPR on clinical outcomes after endovascular thrombectomy (EVT) is unclear. This study aimed to evaluate the association between the GPR at admission and functional outcomes at 90 days after EVT.MethodsWe retrospectively reviewed our database for patients with acute ischemic stroke involving an anterior circulation large-vessel occlusion who received EVT between October 2019 and December 2021. The baseline serum GPR was measured after admission. The primary outcome was a 90-day poor outcome, which was defined as a modified Rankin scale score of 3–6.ResultsA total of 273 patients (mean age, 70.9 ± 11.9 years; 161 men) were finally included for analyses. During the 90-day follow-up, 151 patients (55.3%) experienced an unfavorable outcome. After adjusting for demographic characteristics and other potential confounders, the increased GPR was significantly associated with a higher risk of a 90-day poor outcome (odds ratio, 1.852; 95% confidence interval, 1.276–2.688, p = 0.001). Similar results were observed when the GPR was analyzed as a categorical variable. In addition, the restricted cubic spline observed a positive and linear association between the GPR and poor outcomes at 90 days (p = 0.329 for linearity; p = 0.001 for linearity).ConclusionOur study found that ischemic stroke patients with the higher GPR at admission were more likely to have an unfavorable prognosis at 3 months, suggesting that GPR may be a potential prognostic biomarker for ischemic stroke after EVT.

Abstract Background The evidence of mechanical thrombectomy (MT) in basilar artery occlusion (BAO) was limited. This study aimed to develop dynamic and visual nomogram models to predict the unfavorable outcome of MT in BAO online. Methods BAO patients treated with MT were screened. Preoperative and postoperative nomogram models were developed based on clinical parameters and imaging features. An independent dataset was collected to perform external validation. Web‐based calculators were constructed to provide convenient access. Results A total of 127 patients were included in the study, and 117 of them were eventually included in the analysis. The nomogram models showed robust discrimination, with an area under the receiver operating characteristic (ROC) of 0.841 (preoperative) and 0.916 (postoperative). The calibration curves showed good agreement. The preoperative predictors of an unfavorable outcome were previous stroke, the National Institutes of Health Stroke Scale (NIHSS) at admission, and the posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc‐ASPECTS). The postoperative predictors were previous stroke, NIHSS at 24 h, and pc‐ASPECTS. Conclusion Dynamic and visual nomograms were constructed and validated for the first time for BAO patients treated with MT, which provided precise predictions for the risk of an unfavorable outcome. The preoperative model may assist clinicians in selecting eligible patients, and the postoperative model may facilitate individualized poststroke management.

Abstract Acute ischemic stroke (AIS) is a global cerebrovascular disease with high disability and mortality, which has no effective therapy. Studies have demonstrated that astrocyte-derived exosomes (ADEXs) provided neuroprotection in experimental stroke models. Nevertheless, the role of exosomes derived from oxygen-glucose-deprivation/reoxygenation-stimulated astrocytes (OGD/R-stimulated astrocytes; OGD/R-ADEXs) in AIS remains largely unknown. Here, we found that OGD/R-ADEXs significantly reduced OGD/R-induced neuronal death and promoted neuronal autophagy. These effects were reversed when astrocytes were pretreated with GW4869, an exosome secretion inhibitor, or when hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) was knocked down. Neuroprotection was also observed during treatment with OGD/R-ADEXs in vivo. Further studies showed that Nampt, played a vital effect in the regulation of autophagy, was significantly increased in OGD/R-ADEXs. Knockdown of Nampt in astrocytes abolished the above-mentioned effects of OGD/R-ADEXs. Mechanistically, Nampt increased autophagy and decreased cell death by modulating AMPK/mTOR signaling, which recognized as a key signaling pathway of autophagy after AIS. Collectively, these results showed that Nampt released by OGD/R-ADEXs ameliorated acute ischemic stroke during neuronal injury by targeting AMPK/mTOR signaling to induce autophagy. Our study revealed a new key factor in the secretion of exosomes by OGD/R astrocytes, which regulated autophagy and induced neuroprotection in a mouse stroke model.

BackgroundSymptomatic intracranial atherosclerotic stenosis (sICAS) is one of the common causes of ischemic stroke. However, the treatment of sICAS remains a challenge in the past with unfavorable findings. The purpose of this study was to explore the effect of stenting versus aggressive medical management on preventing recurrent stroke in patients with sICAS.MethodsWe prospectively collected the clinical information of patients with sICAS who underwent percutaneous angioplasty and/or stenting (PTAS) or aggressive medical therapy from March 2020 to February 2022. Propensity score matching (PSM) was employed to ensure well-balanced characteristics of two groups. The primary outcome endpoint was defined as recurrent stroke or transient ischemic attack (TIA) within 1 year.ResultsWe enrolled 207 patients (51 in the PTAS and 156 in the aggressive medical groups) with sICAS. No significant difference was found between PTAS group and aggressive medical group for the risk of stroke or TIA in the same territory beyond 30 days through 6 months (P = 0.570) and beyond 30 days through 1 year (P = 0.739) except for within 30 days (P = 0.003). Furthermore, none showed a significant difference for disabling stroke, death and intracranial hemorrhage within 1 year. These results remain stable after adjustment. After PSM, all the outcomes have no significant difference between these two groups.ConclusionThe PTAS has similar treatment outcomes compared with aggressive medical therapy in patients with sICAS across 1-year follow-up.

Background: This study aimed to examine the association of lipoprotein(a) [Lp(a)] level with the burden of cerebral small vessel disease (CSVD) in patients with Alzheimer’s disease (AD). Methods: Data from 111 consecutive patients with AD admitted to Nanjing First Hospital from 2015 to 2022 were retrospectively analyzed in this study. Serum Lp(a) concentrations were grouped into tertiles (T1–T3). Brain magnetic resonance imaging (MRI) was rated for the presence of CSVD, including enlarged perivascular spaces (EPVS), lacunes, white-matter lesions, and cerebral microbleeds (CMBs). The CSVD burden was calculated by summing the scores of each MRI marker at baseline. A binary or ordinal logistic regression model was used to estimate the relationship of serum Lp(a) levels with CSVD burden and each MRI marker. Results: Patients with higher tertiles of Lp(a) levels were less likely to have any CSVD (T1, 94.6%; T2, 78.4%; T3, 66.2%; p = 0.013). Multivariable analysis found that Lp(a) levels were inversely associated with the presence of CSVD (T2 vs. T1: adjusted odds ratio [aOR] 0.132, 95% confidence interval [CI] 0.018–0.946, p = 0.044; T3 vs. T1: aOR 0.109, 95% CI 0.016–0.737, p = 0.023) and CSVD burden (T3 vs. T1: aOR 0.576, 95% CI 0.362–0.915, p = 0.019). The independent relationship between Lp(a) levels and individual CSVD features was significant for moderate-to-severe EPVS in the centrum semiovale (T2 vs. T1: aOR 0.059, 95% CI 0.006–0.542, p = 0.012; T3 vs. T1: aOR 0.029, 95% CI 0.003–0.273, p = 0.002) and CMBs (T3 vs. T1: aOR 0.144, 95% CI 0.029–0.716, p = 0.018). Conclusions: In this study, serum Lp(a) level was inversely associated with CSVD in AD patients.

Abstract Background Mechanical thrombectomy has been widely performed for large vessel occlusion stroke. The present study aimed to determine whether cumulative experience could improve thrombectomy outcomes. Methods In this retrospective single-center analysis, patients who underwent mechanical thrombectomy with the Solitaire stent in 3 years from 25 April 2015 were enrolled in the current study. Patients’ characteristics, durations of admission and treatment, recanalization rates, clinical outcomes, and hemorrhage transformation rates were compared among the 3 years. Logistic analysis was used to analyze the independent correlation of the years and procedural outcomes. Results A total of 222 patients underwent mechanical thrombectomy in the 3 years: 50 in the first year, 68 in the second year, and 104 in the third year. Door-to-puncture time (P

ObjectiveEndovascular treatment (EVT) is, to date, the most promising treatment of vertebrobasilar artery occlusion (VBAO). The study aimed to determine the influence of perioperative glucose levels on clinical outcomes in patients with acute VBAO treated with EVT.MethodsWe retrospectively collected consecutive VBAO patients received EVT in 21 stroke centers in China. The associations between perioperative glycemic indicators (including fasting blood glucose[FBG], admission hyperglycemia, stress hyperglycemia ratio [SHR] and short-term glycemic variability [GV]) and various clinical outcomes were analyzed in all patients and subgroups stratified by diabetes mellitus (DM).ResultsA total of 569 patients were enrolled. Admission hyperglycemia significantly correlated with increased risk of symptomatic intracranial hemorrhage (sICH) (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.40-7.46), poor functional outcomes at 90 days (OR 1.91, 95%CI: 1.15-3.18) and 1 year (OR 1.96, 95%CI: 1.20-3.22). Similar significant correlations exist between FBG, SHR, GV and all the adverse outcomes except higher levels GV was not associated with increased risk of sICH (OR 1.04, 95% CI: 0.97-1.12). Subgroup analyses showed that admission hyperglycemia, FBG and SHR were significantly associated with adverse outcomes in non-diabetic patients, but not in DM patients. While, GV was associated with poor functional outcomes regardless of diabetes history.ConclusionsAdmission hyperglycemia, FBG, SHR and short-term GV in VBAO patients treated with EVT were associated with adverse outcomes. The results suggested that comprehensive evaluation and appropriate management of perioperative glucose might be important for patients with VBAO and treatment with EVT.

Background and purposeData on adhesion molecule levels in patients treated with mechanical thrombectomy (MT) are scarce. We aimed to evaluate the association among adhesion molecule levels, symptomatic intracranial hemorrhage (sICH), and clinical outcome and to determine whether the sICH influences the association of adhesion molecules with functional outcome.MethodsPatients with large artery occlusion in the anterior circulation and treated with MT were prospectively recruited. Adhesion molecules, such as soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) were tested. An unfavorable outcome was defined as a 90-day modified Rankin Scale (mRS) score of 3–6. The sICH was diagnosed according to the Heidelberg Bleeding Classification within 72 h of endovascular treatment (EVT).ResultsOf the 310 enrolled patients (mean age, 68.5 years; 198 men), 46 (14.8%) experienced sICH and 173 (55.8%) experienced an unfavorable outcome at 90 days. After adjusting for potential confounders, patients with higher sVCAM-1 and sE-selectin levels had an increasing trend of sICH [4th quartile vs. 1st quartile for sVCAM-1; odds ratio (OR), 2.766, p = 0.085; sE-selectin; OR, 2.422, p = 0.086] and poor outcome (4th quartile vs. 1st quartile for sVCAM-1; OR, 2.614, p = 0.025; sE-selectin; OR, 2.325, p = 0.046). Furthermore, the sICH might partially mediate the worse functional outcome in patients with higher adhesion molecules levels (Sobel test, p < 0.001 for sVCAM-1 and p = 0.007 for sE-selectin).ConclusionsThere were significant relationships between levels of adhesion molecules and a 90-day poor outcome in patients with ischemic stroke treated with MT, which was partially mediated by sICH.

Background: Stroke-associated pneumonia (SAP) is a common stroke complication, and the changes in the gut microbiota composition may play a role. Our study aimed to evaluate the predictive ability of gut microbiota for SAP. Methods: Acute ischemic stroke patients were prospectively enrolled and divided into two groups based on the presence or absence of SAP. The composition of gut microbiota was characterized by the 16S RNA Miseq sequencing. The gut microbiota that differed significantly between groups were incorporated into the conventional risk scores, the Acute Ischemic Stroke-Associated Pneumonia Score (AIS-APS), and the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity Score (A2DS2). The predictive performances were assessed in terms of the area under the curve (AUC), the Net Reclassification Improvement (NRI), and the Integrated Discrimination Improvement (IDI) indices. Results: A total of 135 patients were enrolled, of whom 43 had SAP (31%). The short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroides, Fusicatenibacter, and Butyricicoccus, were decreased in the SAP group. The integrated models showed better predictive ability for SAP (AUC = 0.813, NRI = 0.333, p = 0.052, IDI = 0.038, p = 0.018, for AIS-APS; AUC = 0.816, NRI = 0.575, p < 0.001, IDI = 0.043, p = 0.007, for A2DS2) in comparison to the differential genera (AUC = 0.699) and each predictive score (AUCAISAPS = 0.777; AUCA2DS2 = 0.777). Conclusions: The lower abundance of SCFAs-producing gut microbiota after acute ischemic stroke was associated with SAP and may play a role in SAP prediction.

Background and Purpose: Little is known about the effect of soluble adhesion molecules on malignant brain edema (MBE) after endovascular thrombectomy (EVT). This study aimed to explore the association between serum concentrations of E-selectin and the risk of MBE in patients who received EVT. Methods: Patients with a large vessel occlusion stroke in the anterior circulation who underwent EVT were prospectively recruited. Serum soluble E-selectin concentrations were measured after admission for all patients. MBE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 h after surgery. Multivariate logistic regression analyses were performed to determine the association between E-selectin levels and the risk of MBE. Results: Among the 261 included patients (mean age, 69.7 ± 12.3 years; 166 males), 59 (22.6%) developed MBE. Increasing circulating E-selectin levels were associated with an increased risk of MBE after multivariable adjustment (odds ratios [OR], highest vs. lowest quartile: 3.593; 95% confidence interval [CI], 1.178−10.956; p = 0.025). We further observed a significantly positive association between E-selectin and MBE (per 1-standard deviation increase; OR, 1.988; 95% CI, 1.379−2.866, p = 0.001) when the E-selectin levels were analyzed as a continuous variable. Furthermore, the restricted cubic spline demonstrated a linear correlation between serum E-selectin levels and the risk of MBE (p < 0.001 for linearity). Conclusions: In this prospective study, circulating levels of E-selectin were associated with an increased risk of MBE after EVT. Further mechanistic studies are warranted to elucidate the pathophysiology underlying this association.

Background and purposeFutile recanalization occurs when the endovascular thrombectomy (EVT) is a technical success but fails to achieve a favorable outcome. This study aimed to use machine learning (ML) algorithms to develop a pre-EVT model and a post-EVT model to predict the risk of futile recanalization and to provide meaningful insights to assess the prognostic factors associated with futile recanalization.MethodsConsecutive acute ischemic stroke patients with large vessel occlusion (LVO) undergoing EVT at the National Advanced Stroke Center of Nanjing First Hospital (China) between April 2017 and May 2021 were analyzed. The baseline characteristics and peri-interventional characteristics were assessed using four ML algorithms. The predictive performance was evaluated by the area under curve (AUC) of receiver operating characteristic and calibration curve. In addition, the SHapley Additive exPlanations (SHAP) approach and partial dependence plot were introduced to understand the relative importance and the influence of a single feature.ResultsA total of 312 patients were included in this study. Of the four ML models that include baseline characteristics, the “Early” XGBoost had a better performance {AUC, 0.790 [95% confidence intervals (CI), 0.677–0.903]; Brier, 0.191}. Subsequent inclusion of peri-interventional characteristics into the “Early” XGBoost showed that the “Late” XGBoost performed better [AUC, 0.910 (95% CI, 0.837–0.984); Brier, 0.123]. NIHSS after 24 h, age, groin to recanalization, and the number of passages were the critical prognostic factors associated with futile recanalization, and the SHAP approach shows that NIHSS after 24 h ranks first in relative importance.ConclusionsThe “Early” XGBoost and the “Late” XGBoost allowed us to predict futile recanalization before and after EVT accurately. Our study suggests that including peri-interventional characteristics may lead to superior predictive performance compared to a model based on baseline characteristics only. In addition, NIHSS after 24 h was the most important prognostic factor for futile recanalization.

ObjectiveTo develop a prognostic prediction model of endovascular treatment (EVT) for acute ischemic stroke (AIS) induced by large-vessel occlusion (LVO), this study applied machine learning classification model light gradient boosting machine (LightGBM) to construct a unique prediction model.MethodsA total of 973 patients were enrolled, primary outcome was assessed with modified Rankin scale (mRS) at 90 days, and favorable outcome was defined using mRS 0–2 scores. Besides, LightGBM algorithm and logistic regression (LR) were used to construct a prediction model. Then, a prediction scale was further established and verified by both internal data and other external data.ResultsA total of 20 presurgical variables were analyzed using LR and LightGBM. The results of LightGBM algorithm indicated that the accuracy and precision of the prediction model were 73.77 and 73.16%, respectively. The area under the curve (AUC) was 0.824. Furthermore, the top 5 variables suggesting unfavorable outcomes were namely admitting blood glucose levels, age, onset to EVT time, onset to hospital time, and National Institutes of Health Stroke Scale (NIHSS) scores (importance = 130.9, 102.6, 96.5, 89.5 and 84.4, respectively). According to AUC, we established the key cutoff points and constructed prediction scale based on their respective weightings. Then, the established prediction scale was verified in raw and external data and the sensitivity was 80.4 and 83.5%, respectively. Finally, scores >3 demonstrated better accuracy in predicting unfavorable outcomes.ConclusionPresurgical prediction scale is feasible and accurate in identifying unfavorable outcomes of AIS after EVT.

High-resolution magnetic resonance imaging (HRMRI) is the most important and popular vessel wall imaging technique for the direct assessment of vessel wall and cerebral arterial disease. It can identify the cause of stroke in high-risk plaques and differentiate the diagnosis of head and carotid artery dissection, including inflammation, Moya Moya disease, cerebral aneurysm, vasospasm after subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, blunt cerebrovascular injury, cerebral arteriovenous malformations, and other stenosis or occlusion conditions. Through noninvasive visualization of the vessel wall in vitro, quantified assessment of luminal stenosis and pathological features of the vessel wall can provide clinicians with further disease information. In this report, technical considerations of HRMRI are discussed, and current clinical applications of HRMRI are reviewed.

Early neurologic deterioration (END) is a common and feared complication for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). This study aimed to develop an interpretable machine learning (ML) model for individualized prediction to predict END in AIS patients treated with MT. The retrospective cohort of AIS patients who underwent MT was from two hospitals. ML methods applied include logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver operating characteristic curve (AUC) was the main evaluation metric used. We also used Shapley Additive Explanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) to interpret the result of the prediction model. A total of 985 patients were enrolled in this study, and the development of END was noted in 157 patients (15.9%). Among the used models, XGBoost had the highest prediction power (AUC = 0.826, 95% CI 0.781–0.871). The Delong test and calibration curve indicated that XGBoost significantly surpassed those of the other models in prediction. In addition, the AUC in the validating set was 0.846, which showed a good performance of the XGBoost. The SHAP method revealed that blood glucose was the most important predictor variable. The constructed interpretable ML model can be used to predict the risk probability of END after MT in AIS patients. It may help clinical decision making in the perioperative period of AIS patients treated with MT.

Abstract Background Approximately 10% of patients would develop symptomatic intracranial hemorrhage (sICH) after endovascular therapy. The aim of our study was to explore the ability of hypersensitive C-reactive protein-albumin ratio (HAR) in predicting sICH after endovascular therapy. Methods From April 2016 to December 2018, 334 consecutive patients with anterior circulation infarction undergoing endovascular therapy were enrolled in our study. sICH was defined using Heidelberg bleeding classification after endovascular therapy. Multiple regression analysis was used to investigate the potential risk factors of sICH after endovascular therapy. We used receiver operating characteristic curve analysis and nomogram analysis to assess the overall discriminative ability of the HAR in predicting sICH after endovascular therapy. Results Among these 334 patients enrolled, 37 (11.1%) patients with anterior circulation infarction were identified with sICH after endovascular therapy. Univariate logistic regression analysis demonstrated that patients with higher levels of HAR may be inclined to develop sICH (odds ratio, 10.994; 95% confidence interval, 4.567–26.463; P = 0.001). This association remained significant even after adjustment for potential confounders. Also, a cutoff value of 0.526× 10− 3 for HAR was detected in predicting sICH (area under curve, 0.763). Furthermore, nomogram analysis also suggested that HAR was an indicator of sICH (c-index was 0.890, P

Abstract Background and purpose To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). Methods AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. Results Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238–1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009–1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560–0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643–0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. Conclusions NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.

Abstract Background We aimed to assess the safety and efficacy of endovascular treatment (EVT) in patients with anterior circulation emergent large vessel occlusion (ELVO) beyond 6 h from symptom onset in a real-world cohort of patients in China. Methods We retrospectively examined 305 patients with anterior circulation ELVO treated with EVT. Patients were divided into two groups: treated with known onset within 6 h (n = 238) and beyond 6 h (n = 67). Multivariable logistic regression and ordinal shift analyses were used to evaluate the associations between onset-to-groin puncture time and safety and efficacy outcomes. Results Treatment beyond 6 h was not associated with symptomatic intracranial hemorrhage within 48 h (sICH; odds ratio [OR] 2.03, 95% confidence interval [CI] 0.48–8.57, p = 0.334), in-hospital mortality (OR 1.95, 95% CI 0.48–7.91, p = 0.348), successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b or 3; OR 0.73, 95% CI 0.31–1.73, p = 0.470), favorable functional outcome (modified Rankin Scale score 0–2; OR 0.55, 95% CI 0.25–1.23, p = 0.145), and functional improvement (modified Rankin Scale shift by 1-point decrease; common OR 0.80, 95%CI 0.45–1.42, p = 0.450) at 3 months compared with treatment within 6 h. Futher interaction analysis showed that stroke etiology did not modify the associations between onset-to-groin puncture time and outcomes (p > 0.05). Conclusions In this real-world study, after careful assessment, EVT beyond 6 h from known stroke onset was safe, effective and had comparable short-term outcomes to EVT within 6 h.

Abstract Background For acute ischemic stroke (AIS) patient receiving mechanical thrombectomy (MT), renal dysfunction was an independent risk factor of contrast-induced nephropathy which may affect clinical outcomes. However, the influence of renal function on stroke outcomes is still controversial. Thus, we aim to investigate the association between renal function and outcomes of AIS patients receiving MT. Methods All consecutive stroke patients receiving MT were included in a prospective stroke registry in China from April 2015 to February 2019. Estimated glomerular filtration rate (eGFR) was measured on admission and categorized into G1 (≥ 90 ml/min/1.73 m2), G2 (60–89 ml/min/1.73 m2), G3a (45–59 ml/min/1.73 m2) and G3b-5 (≤44 ml/min/1.73 m2). Multivariable logistic regression analysis was performed to evaluate the association between eGFR and recanalization rate (thrombolysis in cerebral infarction scale 2b-3), symptomatic intracranial hemorrhage (sICH), death in hospital, death at 3 months and poor functional outcome (modified Rankin Scale 3–6 at 3 months). Results A total of 373 patients were included in the study. Of them, 130 (34.9%) patients were in the eGFR group G1, 170 (45.6%) in G2, 46 (12.3%) in G3a, 27 (7.2%) in G3b–5. In multivariable logistic regression analysis, reduced eGFR was associated with increased risk of sICH (G3a, p = 0.016) and 3-month death (G3b–5, p = 0.025). However, no significant effects were observed between reduced eGFR and the risk of recanalization rate (p = 0.855), death in hospital (p = 0.970), and poor functional outcome (p = 0.644). Conclusions For AIS patients underwent MT, reduced eGFR was associated with increased risk of sICH and 3-month death. However, there were no appreciable effects of reduced eGFR on recanalization rate, death in hospital and 3-month functional outcome.

IntroductionConcern over the potential severe bleeding risk of dual antiplatelet therapy for patients with minor stroke after intravenous thrombolysis (IVT) leads to different antiplatelet strategies in the secondary prevention of stroke. Our aim was to investigate the effect of dual antiplatelet therapy on patients with minor ischemic stroke receiving IVT.MethodsFrom November 2016 to April 2021, a total of 855 consecutive patients who received IVT were observed. We collected and analyzed demographic characteristics, medical history, clinical information, and important time metrics of patients with minor ischemic stroke. Comparative and multivariate logistic regression analyses were used to explore the clinical significance of single or dual antiplatelet therapy after IVT. Propensity score matching analyses (1:1 matching including baseline characteristics of patients) were also performed.ResultsA total of 245 patients were enrolled in the study (118 patients in the single antiplatelet therapy group and 127 patients in the dual antiplatelet group). No significant difference was found in baseline characteristics except stroke etiology (p < 0.001) for patients with minor stroke. The dual antiplatelet group showed a higher proportion of 90-day modified Rankin Scale (mRS) (0–1) than the single antiplatelet group (p = 0.030). Furthermore, patients receiving dual antiplatelet therapy had excellent outcomes (90-day mRS 0–1) after adjustment (odds ratio [OR] 2.76, 95% CI 1.27–6.01, p = 0.010). Other secondary outcomes (recurrent stroke within 90 days, symptomatic intracerebral hemorrhage, and early neurological deterioration) were not significantly different between the two groups. These findings were generally consistent in propensity score analyses.ConclusionsDual antiplatelet therapy may be a potential therapeutic approach in patients with minor stroke receiving IVT. Further randomized controlled trials are required to confirm this finding.

BackgroundFluid-attenuated inversion recovery vascular hyperintensity (FVH) can reflect the collateral status, which may be a valuable indicator to predict the functional outcome of acute stroke (AS) patients.MethodsA total of 190 AS patients with large vessel occlusion (LVO) were retrospectively investigated. All patients completed a 6-month follow-up and their modified Rankin Scale (mRS) scores were recorded at 1, 3, and 6 months after intravenous thrombolysis (IVT). Based on their mRS at 3 months, patients were divided into two groups: poor prognosis (131 patients; 68.9% of all subjects) and favorable prognosis (59 patients; 31.1% of all subjects). The death records of 28 patients were also analyzed in the poor prognosis group.Results(1) Univariate and multivariate analyses showed that the higher National Institutes of Health Stroke Scale (NIHSS) score at admission, higher fasting blood glucose, and lower FVH score were independent risk factors to predict the poor prognosis of IVT. (2) Survival analysis indicated that FVH score was the only baseline factor to predict the 6-month survival after IVT. (3) Baseline FVH score had great prediction performance for the prognosis of IVT (area under the curve = 0.853). (4) Baseline FVH score were negatively correlated with the NIHSS score at discharge and mRS score at 1, 3, and 6 months.ConclusionAmong various baseline clinical factors, only the FVH score might have implications for 3-month outcome and 6-month survival of AS patients after IVT. Baseline FVH score showed great potential to predict the prognosis of the AS patients.

BackgroundAlterations in the gut microbiota after ischemic stroke have been demonstrated, whereas the effect on stroke outcome remains to be established.MethodsA total of 132 consecutive patients with acute ischemic stroke were prospectively enrolled. Their gut microbiomes within 24 h of admission were profiled using 16S ribosomal RNA (rRNA) gene (V3–V4 region) sequencing. Microbiota comparisons were made between groups with good outcome (n = 105) and poor outcome (n = 27) based on 3-month modified Rankin Scale scores of 0–2 and 3–6. Propensity score-matching (PSM) analysis was conducted to assess the robustness of our findings. The functional potential was predicted using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt).ResultsPatients in the poor outcome group were characterized by a significant reduction in the alpha diversity (Shannon index, p = 0.025; Simpson index, p = 0.010), an increase in the pathogenic bacteria (e.g., Enterococcaceae and Enterococcus), and a decrease in the short-chain fatty acids (SCFAs)-producing bacteria (e.g., Bacteroidaceae, Ruminococcaceae, and Faecalibacterium) to those with good outcome group (all p < 0.05). Similar results of microbial composition were obtained after PSM. The PICRUSt revealed that the pathway for membrane transport was relatively dominant in patients with poor outcome (p < 0.05).ConclusionThis study demonstrated that stroke patients with 3-month poor outcome had baseline gut microbiota dysbiosis featured by increased pathogenic bacteria and decreased SCFAs-producing bacteria.

Abstract Background A fraction of patients with penetrating artery infarction (PAI) experience progressive motor deficit deterioration (PMD). We sought to investigate the role of high-sensitivity C-reactive protein (hs-CRP) at admission in predicting PMD. Methods From January 2015 to September 2018, consecutive patients with PAI from three centers were prospectively enrolled in this study. PMD was defined as worsening of motor function score by ≥1 point on the National Institutes of Health Stroke Scale during the first 5 days after admission. Multivariable logistic regression analyses were performed to explore the relationship between hs-CRP and PMD in patients with PAI. We also performed receiver operating characteristic curve analysis and constructed a nomogram to assess the overall discriminative ability of hs-CRP in predicting PMD. Results We ultimately included 544 patients (mean age, 65.4 ± 11.8 years). A total of 85 (15.6%) patients were identified to have PMD. Multivariate logistic regression analysis showed that hs-CRP was independently associated with PMD (P = 0.001). The optimal cutoff value for hs-CRP as a predictor for PMD was 3.48 mg/L, with a sensitivity of 73.64% and a specificity of 82.35% (area under curve, 0.792). Moreover, the nomogram we constructed indicated that higher level of hs-CRP was an indicator of PMD (c-index = 0.780, P

Background and Purpose: Treatment for mild stroke remains an open question. We aim to develop a decision support tool based on machine learning (ML) algorithms, called DAMS (Disability After Mild Stroke), to identify mild stroke patients who would be at high risk of post-stroke disability (PSD) if they only received medical therapy and, more importantly, to aid neurologists in making individual clinical decisions in emergency contexts.Methods: Ischemic stroke patients were prospectively recorded in the National Advanced Stroke Center of Nanjing First Hospital (China) between July 2016 and September 2020. The exclusion criteria were patients who received thrombolytic therapy, age 5. The primary outcome was PSD, corresponding to 3-month mRS ≥ 2. We developed five ML models and assessed the area under curve (AUC) of receiver operating characteristic, calibration curve, and decision curve analysis. The optimal ML model was selected to be DAMS. In addition, SHapley Additive exPlanations (SHAP) approach was introduced to rank the feature importance. Finally, rapid-DAMS (R-DAMS) was constructed for a more urgent situation based on DAMS.Results: A total of 1,905 mild stroke patients were enrolled in this study, and patients with PSD accounted for 23.4% (447). There was no difference in AUCs between the five models (ranged from 0.691 to 0.823). Although there was similar discriminative performance between ML models, the support vector machine model exhibited higher net benefit and better calibration (Brier score, 0.159, calibration slope, 0.935, calibration intercept, 0.035). Therefore, this model was selected for DAMS. In addition, SHAP approach showed that the most crucial feature was NIHSS on admission. Finally, R-DAMS was constructed and there was similar discriminative performance between R-DAMS and DAMS, but the former performed worse on calibration.Conclusions: DAMS and R-DAMS, as prediction-driven decision support tools, were designed to aid clinical decision-making for mild stroke patients in emergency contexts. In addition, even within a narrow range of baseline scores, NIHSS on admission is the strongest feature that contributed to the prediction.

Stroke induces disorder of gut microbiota, however, whether this disorder differs according to stroke severity and its role in the evolution and outcome of stroke is currently unknown. Here we explored the composition and structure of fecal microbiome based on 68 acute ischemic stroke patients presenting with minor symptoms (admission National Institute of Health Stroke Scale (NIHSS) ≤ 3) and 67 patients with non-minor stroke (admission NIHSS 4-34) using high-throughput Illumina sequencing of the 16S rRNA. There was no significant difference in α-diversity indices, but the principal coordinate analysis of the microbiota indicated clear separation of the two groups. The significantly enriched butyrate-producing genus Roseburia in the minor stroke group was negatively correlated with fasting glucose, while the Erysipelotrichaceae incertae sedis abundant in non-minor stroke patients was positively correlated with stress hyperglycemia (i.e. fasting glucose/glycated hemoglobin ratio). Moreover, the relative abundance of genus Roseburia was also significantly associated with the dynamic changes of NIHSS score, as well as short-term and long-term functional outcomes. Our results suggested that stroke affects microbiota composition in a manner differentiated by stroke severity, and the enrichment of genus Roseburia may play a protective role in stroke evolution and outcome. Our findings strengthen the relevance of specific taxa for stroke severity that might allow targeted therapy in acute ischemic stroke.

Objective: Higher fasting glucose is thought to be associated with adverse outcome in patients receiving endovascular treatment (EVT), while the effect of glycosylated hemoglobin (HbA1c) on outcome is controversial. We combined fasting blood glucose (FBG) with HbA1c and evaluated their relationship with the three-month functional outcome in patients who underwent EVT. Methods: Data from 739 consecutive ischemic stroke patients who underwent EVT from April 2015 to August 2021 were retrospectively reviewed. HbA1c was used to estimate the chronic glucose level according to the following formula: chronic glucose level (mg/dL) = 28.7 × HbA1c (%) − 6.7. Patients were split into two groups in accordance with the three-month modified Rankin Scale (mRS). Univariate and multivariate analyses were utilized to investigate the association of outcome with blood glucose and to identify other predictors of prognosis. Results: Patients with poor outcome had significantly higher FBG, chronic glycemia, FBG/chronic glycemic ratio, and difference between FBG and chronic glycemia (ΔA-C). FBG, the FBG/chronic glycemic ratio, and ΔA-C remained to be associated with poor outcome after adjustment. We then established a glycemia-based nomogram with a concordance index of 0.841, and it showed favorable clinical utility according to decision curve analysis. Conclusions: Glycemia after EVT was connected with the functional outcome and a nomogram based on glycemia may be used to predict prognosis in stroke patients treated with EVT.

Aging-related neurocognitive disorder (NCD) is a growing health concern. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite from dietary precursors, might emerge as a promising biomarker of cognitive dysfunction within the context of brain aging and NCD. TMAO may increase among older adults, Alzheimer’s disease patients, and individuals with cognitive sequelae of stroke. Higher circulating TMAO would make them more vulnerable to age- and NCD-related cognitive decline, via mechanisms such as promoting neuroinflammation and oxidative stress, and reducing synaptic plasticity and function. However, these observations are contrary to the cognitive benefit reported for TMAO through its positive effects on blood–brain barrier integrity, as well as from the supplementation of TMAO precursors. Hence, current disputable evidence does not allow definite conclusions as to whether TMAO could serve as a critical target for cognitive health. This article provides a comprehensive overview of TMAO documented thus far on cognitive change due to aging and NCD.

Purpose: The Tonbridge stent is a novel retriever with several design improvements which aim to achieve promising flow reperfusion in the treatment of acute ischemic stroke (AIS). We conducted a randomized controlled, multicenter, non-inferiority trial to compare the safety and efficacy of the Tonbridge stent with the Solitaire FR.Methods: AIS patients aged 18–85 years with large vessel occlusion in anterior circulation who could undergo puncture within 6 h of symptom onset were included. Randomization was performed on a 1:1 ratio to thrombectomy with either the Tonbridge stent or the Solitaire FR. The primary efficacy endpoint was successful reperfusion using a modified thrombolysis in cerebral infarction score (mTICI) of 2b/3. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 24 ± 6 h and all-cause mortality within 90 days. A clinically relevant non-inferiority margin of 12% was chosen as the acceptable difference between groups. Secondary endpoints included time from groin puncture to reperfusion, National Institutes of Health Stroke Scale (NIHSS) score at 24 h and at 7 days, and a modified Rankin Scale (mRS) score of 0–2 at 90 days.Results: A total of 220 patients were enrolled; 104 patients underwent thrombectomy with the Tonbridge stent and 104 were treated with the Solitaire FR. In all test group patients, the Tonbridge was used as a single retriever without rescuing by other thrombectomy devices. Angioplasty with balloon and/or stent was performed in 26 patients in the Tonbridge group and 16 patients in the Solitaire group (p = 0.084). Before angioplasty, 86.5% of those in the Tonbridge group and 81.7% of those in the Solitaire group reached successful reperfusion (p = 0.343). Finally, more patients in the Tonbridge group achieved successful reperfusion (92.3 vs. 84.6%, 95% CI of difference value 0.9–16.7%, p < 0.0001). There were no significant differences on sICH within 24 ± 6 h between the two groups. All-cause mortality within 90 days was 13.5% in the Tonbridge group and 16.3% in the Solitaire group (p = 0.559). We noted no significant differences between groups on the NIHSS at either 24 h or 7 days and the mRS of 0–2 at 90 days.Conclusion: The trial indicated that the Tonbridge stent was non-inferior to the Solitaire FR within 6 h of symptom onset in cases of large vessel occlusion stroke.Clinical Trial Registration:ClinicalTrials.gov, number: NCT03210623.

Abstract Background Early prediction of unfavorable outcome after ischemic stroke is of great significance to the clinical and therapeutic management. A nomogram is a better visual tool than earlier models and prognostic scores to predict clinical outcomes, which incorporates different factors to develop a graphic continuous scoring system and calculates accurately the risk probability of poor outcome entirely based on individual characteristics. However, to date, no nomogram models have been found to predict the probability of 6-month poor outcome after ischemic stroke. We aimed to develop and validate a nomogram for individualized prediction of the probability of 6-month unfavorable outcome in Chinese patients with ischemic stroke. Methods Based on the retrospective stroke registry, a single-center study which included 499 patients from May, 2013 to May, 2018 was conducted in Nanjing First Hospital (China) for ischemic stroke within 12 h of symptoms onset. The main outcome measure was 6-month unfavorable outcome (mRS > 2). To generate the nomogram, NIHSS score on admission, Age, previous Diabetes mellitus and crEatinine (NADE) were integrated into the model. We assessed the discriminative performance by using the area under the curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer–Lemeshow test. Results A visual NADE nomogram was constructed that NIHSS score on admission (OR: 1.190, 95%CI: 1.125–1.258), age (OR: 1.068, 95%CI: 1.045–1.090), previous diabetes mellitus (OR: 1.995, 95%CI: 1.236–3.221) and creatinine (OR: 1.010, 95%CI: 1.002–1.018) were found to be significant predictors of 6-month unfavorable outcome after acute ischemic stroke in Chinese patients. The AUC–ROC of nomogram was 0.791. Calibration was good (p = 0.4982 for the Hosmer–Lemeshow test). Conclusion The NADE is the first nomogram developed and validated in Chinese ischemic stroke patients to provide an individual, visual and precise prediction of the risk probability of 6-month unfavorable outcome.

The unfavorable outcome of acute ischemic stroke (AIS) with large vessel occlusion (LVO) is related to clinical factors at multiple time points. However, predictive models used for dynamically predicting unfavorable outcomes using clinically relevant preoperative and postoperative time point variables have not been developed. Our goal was to develop a machine learning (ML) model for the dynamic prediction of unfavorable outcomes. We retrospectively reviewed patients with AIS who underwent a consecutive mechanical thrombectomy (MT) from three centers in China between January 2014 and December 2018. Based on the eXtreme gradient boosting (XGBoost) algorithm, we used clinical characteristics on admission (“Admission” Model) and additional variables regarding intraoperative management and the postoperative National Institute of Health stroke scale (NIHSS) score (“24-Hour” Model, “3-Day” Model and “Discharge” Model). The outcome was an unfavorable outcome at the three-month mark (modified Rankin scale, mRS 3–6: unfavorable). The area under the receiver operating characteristic curve and Brier scores were the main evaluating indexes. The unfavorable outcome at the three-month mark was observed in 156 (62.0%) of 238 patients. These four models had a high accuracy in the range of 75.0% to 87.5% and had a good discrimination with AUC in the range of 0.824 to 0.945 on the testing set. The Brier scores of the four models ranged from 0.122 to 0.083 and showed a good predictive ability on the testing set. This is the first dynamic, preoperative and postoperative predictive model constructed for AIS patients who underwent MT, which is more accurate than the previous prediction model. The preoperative model could be used to predict the clinical outcome before MT and support the decision to perform MT, and the postoperative models would further improve the predictive accuracy of the clinical outcome after MT and timely adjust therapeutic strategies.

Background and Purpose: Accurate prediction of functional outcome after stroke would provide evidence for reasonable post-stroke management. This study aimed to develop a machine learning-based prediction model for 6-month unfavorable functional outcome in Chinese acute ischemic stroke (AIS) patient.Methods: We collected AIS patients at National Advanced Stroke Center of Nanjing First Hospital (China) between September 2016 and March 2019. The unfavorable outcome was defined as modified Rankin Scale score (mRS) 3–6 at 6-month. We developed five machine-learning models (logistic regression, support vector machine, random forest classifier, extreme gradient boosting, and fully-connected deep neural network) and assessed the discriminative performance by the area under the receiver-operating characteristic curve. We also compared them to the Houston Intra-arterial Recanalization Therapy (HIAT) score, the Totaled Health Risks in Vascular Events (THRIVE) score, and the NADE nomogram.Results: A total of 1,735 patients were included into this study, and 541 (31.2%) of them had unfavorable outcomes. Incorporating age, National Institutes of Health Stroke Scale score at admission, premorbid mRS, fasting blood glucose, and creatinine, there were similar predictive performance between our machine-learning models, while they are significantly better than HIAT score, THRIVE score, and NADE nomogram.Conclusions: Compared with the HIAT score, the THRIVE score, and the NADE nomogram, the RFC model can improve the prediction of 6-month outcome in Chinese AIS patients.

Abstract Objectives The accuracy of cognitive screening tools to detect poststroke cognitive impairment (PSCI) was investigated using various neuropsychological definitions. Methods Hospital‐based stroke patients underwent a comprehensive neuropsychological assessment. The rate of PSCI was estimated using thresholds of 1, 1.5, or 2 standard deviations below the normal control and memory impairment defined by a single or multiple tests. Meanwhile, the diagnostic accuracy of cognitive screening through face‐to‐face assessment using the Mini‐Mental State Examination (MMSE) and the Montreal Cognitive Assessment Scale (MoCA), and telephone assessment using a 5‐minute NINDS‐Canadian Stroke Network (NINDS‐CSN) scale and a six‐item screener (SIS), was both tested under different definitions, with the optimal cutoff selected based on the highest Youden index. Results In stroke patients, the rate of PSCI ranged from 46.3% to 76.3% upon different definitions. The face‐to‐face MoCA was more consistent with the comprehensive cognitive assessment compared to MMSE. The optimal cutoff of PSCI was MMSE ≤ 27 and MoCA ≤ 19. For the telephone tests, the 5‐minute NINDS‐CSN assessment was more reliable, and the optimal cutoff was ≤23, while for SIS ≤ 4. Conclusions Cognitive screening tools including the face‐to‐face MMSE and MoCA, together with the telephone assessment of NINDS‐CSN 5‐minute protocol and SIS, were simple and effective for detecting PSCI in stroke patients. The corresponding threshold values for PSCI were 27 points, 19 points, 23 points, and 4 points.

Background and Purpose: Accurate prediction of functional outcomes after stroke would provide evidence for reasonable poststroke management. This study aimed to develop and validate a nomogram for individualized prediction of 1-year unfavorable outcomes in Chinese acute ischemic stroke (AIS) patients.Methods: We gathered AIS patients at the National Advanced Stroke Center of Nanjing First Hospital (China) between August 2014 and May 2017 within 12 h of symptom onset. The outcome measure was 1-year unfavorable outcomes (modified Rankin Scale 3–6). The patients were randomly stratified into the training (66.7%) and testing (33.3%) sets. With the training data, pre-established predictors were entered into a logistic regression model to generate the nomogram. Predictive performance of the nomogram model was evaluated in the testing data by calculating the area under the receiver operating characteristic curve (AUC-ROC), Brier score, and a calibration plot.Results: A total of 807 patients were included into this study, and 262 (32.5%) of them had unfavorable outcomes. Systolic blood pressure, Creatinine, Age, National Institutes of Health Stroke Scale (NIHSS) score on admission, and fasting blood glucose were significantly associated with unfavorable outcomes and entered into the SCANO nomogram. The AUC-ROC of the SCANO nomogram in the testing set was 0.781 (Brier score: 0.166; calibration slope: 0.936; calibration intercept: 0.060).Conclusions: The SCANO nomogram is developed and validated in Chinese AIS patients to firstly predict 1-year unfavorable outcomes, which is simple and convenient for the management of stroke patients.

Background and Purpose: The clinical use of tirofiban for patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) remains controversial. We aimed to evaluate the safety and efficacy of tirofiban combined with MT in AIS patients.Methods: Patients with AIS who underwent MT from January 2014 to December 2018 were enrolled in three stroke units in China. Subgroup analyses were performed based on stroke etiology which was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Safety outcomes were in-hospital intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) and mortality at 3-month. Efficacy outcomes were favorable functional outcome and functional independence at 3-month and neurological improvement at 24 h, 3 d and discharge.Results: In patients with large artery atherosclerosis (LAA) stroke, multivariate analyses revealed that tirofiban significantly decreased the odds of in-hospital ICH (adjusted OR = 0.382, 95% CI 0.180–0.809) and tended to increase the odds of favorable functional outcome at 3-month (adjusted OR = 3.050, 95% CI 0.969–9.598). By contrast, in patients with cardioembolism (CE) stroke, tirofiban was not associated with higher odds of favorable functional outcome at 3-month (adjusted OR = 0.719, 95% CI 0.107–4.807), but significantly decreased the odds of neurological improvement at 24 h and 3d (adjusted OR = 0.185, 95% CI 0.047–0.726; adjusted OR = 0.268, 95% CI 0.087–0.825).Conclusions: Tirofiban combined with MT appears to be safe and effective in LAA patients, but has no beneficial effect on CE patients.

Abstract Background and purpose Intravenous thrombolysis (IVT) has become the standard treatment for acute ischemic stroke within 4.5 hr after symptoms onset. However, a fraction of patients would develop early neurological deterioration (END) after IVT. The aim of our study was to explore the utility of neutrophil–lymphocyte ratio (NLR) in predicting END. Methods From October 2016 to March 2018, 342 consecutive patients with thrombolytic therapy were prospectively enrolled in this study. Blood cell counts were sampled in stroke emergency room before IVT. END was defined as a National Institutes of Health Stroke Scale score increase of ≥4 points within 24 hr after IVT. Multiple regression analysis was used to investigate the potential risk factors of END. We also performed receiver operating characteristic curve analysis and nomogram analysis to assess the overall discriminative ability of the NLR in predicting END. Results Of the 342 patients, 86 (25.1%) participants were identified with END. Univariate logistic regression analysis demonstrated that patients with NLR in the third tertile, compared with the first tertile, were more likely to have END (odds ratio, 9.783; 95% confidence interval [CI], 4.847–19.764; p = .001). The association remained significant even after controlled for potential confounders. Also, a cutoff value of 4.43 for NLR was detected in predicting post‐thrombolysis END with a sensitivity of 70.9% and a specificity of 79.3% (area under curve, 0.779; 95% CI, 0.731–0.822). Furthermore, our established nomogram indicated that higher NLR was an indicator of post‐thrombolysis END (c‐index was 0.789, p

Background Edaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and (+)-borneol, a food additive with an anti-inflammatory effect in animal ischaemic stroke models. This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke (AIS).Methods In this multicentre, randomised, double-blind, multiple-dose, active-controlled, phase II clinical trial, patients with AIS within 48 hours after stroke onset were randomly assigned (1:1:1:1) to low-dose (12.5 mg), medium-dose (37.5 mg) or high-dose (62.5 mg) Edaravone Dexborneol groups, and an active control group with edaravone (30 mg) by 30 min intravenous infusion every 12 hours, for 14 consecutive days. The primary efficacy outcome was the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days and National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 14 days after randomisation. The safety outcome included any adverse event during 90 days after treatment.Results Of 385 patients included in the efficacy analysis, 94 were randomised to low-dose group, 97 to medium-dose group, 98 to high-dose group and 96 to the control group. No significant difference was observed among the four groups on mRS score (mRS ≤1, p=0.4054) at 90 days or NIHSS score change at 14 days (p=0.6799). However, a numerically higher percentage of patients with mRSscore ≤1 at 90 days in the medium-dose (69.39%) and high-dose (65.63%) groups was observed than in the control group (60.64%). No significant difference in severe adverse events was found among the four groups (p=0.3815).Conclusions Compared with edaravone alone, Edaravone Dexborneol was safe and well tolerated at all doses, although no significant improvement in functional outcomes was observed at 90days.Trial registration number NCT01929096.

Background and purpose: Futile recanalization occurs when the endovascular thrombectomy (EVT) is a technical success but fails to achieve a favorable outcome. This study aimed to use machine learning (ML) algorithms to develop a pre-EVT model and a post-EVT model to predict the risk of futile recanalization and to provide meaningful insights to assess the prognostic factors associated with futile recanalization. Methods: Consecutive acute ischemic stroke patients with large vessel occlusion (LVO) undergoing EVT at the National Advanced Stroke Center of Nanjing First Hospital (China) between April 2017 and May 2021 were analyzed. The baseline characteristics and peri-interventional characteristics were assessed using four ML algorithms. The predictive performance was evaluated by the area under curve (AUC) of receiver operating characteristic and calibration curve. In addition, the SHapley Additive exPlanations (SHAP) approach and partial dependence plot were introduced to understand the relative importance and the influence of a single feature. Results: A total of 312 patients were included in this study. Of the four ML models that include baseline characteristics, the "Early" XGBoost had a better performance {AUC, 0.790 [95% confidence intervals (CI), 0.677-0.903]; Brier, 0.191}. Subsequent inclusion of peri-interventional characteristics into the "Early" XGBoost showed that the "Late" XGBoost performed better [AUC, 0.910 (95% CI, 0.837-0.984); Brier, 0.123]. NIHSS after 24 h, age, groin to recanalization, and the number of passages were the critical prognostic factors associated with futile recanalization, and the SHAP approach shows that NIHSS after 24 h ranks first in relative importance. Conclusions: The "Early" XGBoost and the "Late" XGBoost allowed us to predict futile recanalization before and after EVT accurately. Our study suggests that including peri-interventional characteristics may lead to superior predictive performance compared to a model based on baseline characteristics only. In addition, NIHSS after 24 h was the most important prognostic factor for futile recanalization. [ABSTRACT FROM AUTHOR]