Autophagy-related 5 in acute ischemic stroke: Variation and linkage with neurofunction, and survival.

OBJECTIVE: Autophagy-related 5 (ATG5) facilitates the pathologic process of acute ischemic stroke (AIS) via multiple ways. This study aimed to identify the association of serum ATG5 with clinical outcomes in AIS patients. METHODS: Serum ATG5 from 280 AIS patients were detected at admission, Day (D)1, D3, D7, D30, and D90 after admission by enzyme-linked immunosorbent assay. The median (interquartile range) follow-up was 21.1 (5.9-43.9) months. Another 50 healthy controls (HCs) were also enrolled for serum ATG5 determination. RESULTS: ATG5 was elevated (p < 0.001) (vs. HCs), and positively correlated with hyperlipidemia (p = 0.016), and the national institutes of health stroke scale score (p = 0.001) in AIS patients. Interestingly, ATG5 was increased from admission to D1, but gradually decreased until D90 (p < 0.001). Besides, 85 (30.4%) and 195 (69.6%) AIS patients were assessed as modified Rankin Scale (mRS) >2 and mRS ≤2 at D90, respectively. ATG5 at admission, D1, D3, D30, and D90 was elevated in AIS patients with mRS >2 versus those with mRS ≤2 (all p < 0.050). ATG5 at admission, D1, D3, D7, D30, or D90 was elevated in relapsed (vs. non-relapsed) or died (vs. survived) AIS patients (all p < 0.050). Recurrence-free survival was shortened in AIS patients with high (≥52.0 ng/mL) ATG5 versus those with low (<52.0 ng/mL) ATG5 at admission, D3, D7, and D30 (all p < 0.050); overall survival was shorter in AIS patients with high (vs. low) ATG5 at D7 and D30 (both p < 0.050). INTERPRETATION: Serum ATG5 elevates at first, thereafter gradually declines, whose elevation associates with neurological dysfunction, recurrence, and death risk in AIS patients.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Differential impacts of admission LDL-cholesterol on early vascular outcomes by ischemic stroke subtypes.

BACKGROUND: Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients. METHODS: This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months. RESULTS: A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (Pinteraction=0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes. CONCLUSION: We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes.

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Safety outcomes of early initiation of antithrombotic agents within 24 h after intravenous alteplase at 0.6 mg/kg.

BACKGROUND: We examined outcome of acute ischemic stroke (AIS) with administration of antithrombotics within 24 h after intravenous low-dose alteplase. METHODS: Consecutive AIS patients who were treated with intravenous alteplase at 0.6 mg/kg from 2005 to 2021 were retrospectively included in our single-center registry. Patients were classified into two groups: those who received antithrombotics within 24 h after intravenous alteplase (early initiation group) and those who did not (control group). Safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH (sICH) within 36 h after onset, and death within 3 months. sICH was defined as any ICH with a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or death within 36 h. RESULTS: Of 1111 patients (women, 426; median age, 76 [interquartile range, 69-83] years; median NIHSS score, 11 [6-19]; cardioembolism, 580 [52.2%]), early initiation group comprised 58 patients (22; 72 [65-80] years; 7 [4-12]; 11 [19.0%]) and control group comprised 1053 patients (404; 77 [69-84] years; 11 [6-19]; 569 [54.1%]). No significant between-group differences were observed in the incidence of any ICH (17.2% vs. 21.6%; adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 0.57-2.44), sICH (0% vs. 0.9%, P = 1.00), or death within 3 months (5.2% vs. 6.7%; aOR, 1.23; 95% CI, 0.36-4.23). CONCLUSIONS: Early initiation of antithrombotics after intravenous alteplase at 0.6 mg/kg did not increase the rate of sICH or death within 3 months and may be used with caution in patients with advanced neurological deterioration.

Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied. METHODS: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality. RESULTS: A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval [CI], 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy. CONCLUSIONS: Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).

Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?

The objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.

Oxygen Saturation and Postoperative Mortality in Patients With Acute Ischemic Stroke Treated by Endovascular Thrombectomy.

BACKGROUND: Monitored anesthesia care (MAC) and general anesthesia (GA) with endotracheal intubation are the 2 most used techniques for patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy. We aimed to test the hypothesis that increased arterial oxygen concentration during reperfusion period is a mechanism underlying the association between use of GA (versus MAC) and increased risk of in-hospital mortality. METHODS: In this retrospective cohort study, data were collected at the Cleveland Clinic between 2013 and 2018. To assess the potential mediation effect of time-weighted average oxygen saturation (Spo2) in first postoperative 48 hours between the association between GA versus MAC and in-hospital mortality, we assessed the association between anesthesia type and post-operative Spo2 tertiles (exposure-mediator relationship) through a cumulative logistic regression model and assessed the association between Spo2 and in-hospital mortality (mediator-outcome relationship) using logistic regression models. Confounding factors were adjusted for using propensity score methods. Both significant exposure-mediator and significant mediator-outcome relationships are needed to suggest potential mediation effect. RESULTS: Among 358 patients included in the study, 104 (29%) patients received GA and 254 (71%) received MAC, with respective hospital mortality rate of 19% and 5% (unadjusted P value <.001). GA patients were 1.6 (1.2, 2.1) (P < .001) times more likely to have a higher Spo2 tertile as compared to MAC patients. Patients with higher Spo2 tertile had 3.8 (2.1, 6.9) times higher odds of mortality than patients with middle Spo2 tertile, while patients in the lower Spo2 tertile did not have significant higher odds compared to the middle tertile odds ratio (OR) (1.8 [0.9, 3.4]; overall P < .001). The significant exposure-mediator and mediator-outcome relationships suggest that Spo2 may be a mediator of the relationship between anesthetic method and mortality. However, the estimated direct effect of GA versus MAC on mortality (ie, after adjusting for Spo2; OR [95% confidence interval {CI}] of 2.1 [0.9-4.9]) was close to the estimated association ignoring Spo2 (OR [95% CI] of 2.2 [1.0-5.1]), neither statistically significant, suggesting that Spo2 had at most a modest mediator role. CONCLUSIONS: GA was associated with a higher Spo2 compared to MAC among those treated by endovascular thrombectomy for AIS. Spo2 values that were higher than the middle tertile were associated with higher odds of mortality. However, GA was not significantly associated with higher odds of death. Spo2 at most constituted a modest mediator role in explaining the relationship between GA versus MAC and mortality.

Day-by-Day Blood Pressure Variability in the Subacute Stage of Ischemic Stroke and Long-Term Recurrence.

BACKGROUND AND PURPOSE: This study aimed to determine whether variability of day-by-day blood pressure (BP) during the subacute stage of acute ischemic stroke is predictive of long-term stroke recurrence. METHODS: We analyzed 7665 patients (mean±SD age: 72.9±13.1 years; women: 42.4%) hospitalized for first-ever ischemic stroke in 7 stroke centers in Fukuoka, Japan, from June 2007 to November 2018. BP was measured daily during the subacute stage (4-10 days after onset). Its mean and coefficient of variation (CV) values were calculated and divided into 4 groups according to the quartiles of these BP parameters. Patients were prospectively followed up for recurrent stroke or all-cause death. The cumulative event rate was calculated with the Kaplan-Meier method. We estimated the hazard ratios and 95% confidence intervals of the events of interest after adjusting for potential confounders and mean BP values using Cox proportional hazards models. The Fine-Gray model was also used to account for the competing risk of death. RESULTS: With a mean (±SD) follow-up duration of 3.9±3.2 years, the rates of recurrent stroke and all-cause death were 3.9 and 9.9 per 100 patient-years, respectively. The cumulative event rates of recurrent stroke and all-cause death increased with increasing CVs of systolic BP and diastolic BP. The systolic BP CV was significantly associated with an increased risk of recurrent stroke after adjusting for multiple confounders and mean BP (hazard ratio [95% CI] for fourth quartile versus first quartile, 1.26 [1.05-1.50]); the risk of recurrent stroke also increased with an increasing systolic BP CV for nonfatal strokes (1.26 [1.05-1.51]) and when death was regarded as a competing risk (1.21 [1.02-1.45]). Similar associations were observed for the diastolic BP CV. CONCLUSIONS: Day-by-day variability of BP during the subacute stage of acute ischemic stroke was associated with an increased long-term risk of recurrent stroke.

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage.

Early brain injury (EBI) is considered an important cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). As a factor in EBI, microcirculatory dysfunction has become a focus of interest, but whether microcirculatory dysfunction is more important than angiographic vasospasm (aVS) remains unclear. Using data from 128 cases, we measured the time to peak (TTP) in several regions of interest on digital subtraction angiography. The intracerebral circulation time (iCCT) was obtained between the TTP in the ultra-early phase (the baseline iCCT) and in the subacute phase and/or at delayed cerebral ischemia (DCI) onset (the follow-up iCCT). In addition, the difference in the iCCT was calculated by subtracting the baseline iCCT from the follow-up iCCT. Univariate analysis showed that DCI was significantly increased in those patients with a prolonged baseline iCCT, prolonged follow-up iCCT, increased differences in the iCCT, and with severe aVS. Poor outcome was significantly increased in patients with prolonged follow-up iCCT and increased differences in the iCCT. Multivariate analysis revealed that increased differences in the iCCT were a significant risk factor that increased DCI and poor outcome. The results suggest that the increasing microcirculatory dysfunction over time, not aVS, causes DCI and poor outcome after aneurysmal aSAH.

An Asian Perspective on Gender Differences in In-Hospital and Long-Term Outcome of Cardiac Mortality and Ischemic Stroke after Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: Gender differences historically exist in cardiovascular disease, with women experiencing higher rates of major adverse cardiovascular events. We investigated these trends in a contemporary Asian cohort, examining the impact of gender differences on cardiac mortality and ischemic stroke after primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). MATERIALS AND METHODS: We analysed 3971 consecutive patients who underwent primary PCI for STEMI retrospectively. The primary outcome was cardiac mortality and ischemic stroke in-hospital, at one year and on longer-term follow up (median follow up 3.62 years, interquartile range 1.03-6.03 years). RESULTS: There were 580 (14.6%) female patients and 3391 (85.4%) male patients. Female patients were older and had higher prevalence of hypertension, diabetes, previous strokes, and chronic kidney disease. Cardiac mortality was higher in female patients during in-hospital (15.5% vs. 6.2%), 1-year (17.4% vs. 7.0%) and longer term follow up (19.9% vs. 8.1%, log-rank test: p < 0.001). Similarly, females had higher incidence of ischemic stroke at in-hospital (2.6% vs. 1.0%), 1-year (3.6% vs. 1.4%) and in the longer-term (6.7% vs. 3.1%) as well (log-rank test: p < 0.001). Female gender remained an independent predictor of in-hospital cardiac mortality (HR 1.395, 95%CI 1.061-1.833, p=0.017) and on longer-term follow-up (HR 1.932 95%CI 1.212-3.080, p=0.006) even after adjusting for confounders. CONCLUSIONS: Females were at higher risk of in-hospital and long-term cardiac mortality and ischemic stroke after PPCI for STEMI. Future studies are warranted to investigate the role of aggressive management of cardiovascular risk factors and follow-up to improve outcomes in the females with STEMI.

Malnutrition on admission increases the in-hospital mortality and length of stay in elder adults with acute ischemic stroke.

PURPOSE: Malnutrition, as determined by the Controlling Nutritional Status (CONUT), has an effect on the 3-month and long-term prognosis of stroke patients. The association between malnutrition and in-hospital mortality has not been well established. We aimed to investigate the relationship between the CONUT score on admission and in-hospital mortality and length of stay (LOS) in elderly patients with acute ischemic stroke (AIS). METHODS: This study analyzed controls and patients with AIS. Malnutrition was determined using the CONUT score. A CONUT score of 5-12 was defined as undernutrition status. Based on the CONUT scores, the patients were divided into the low CONUT (0-4) and high CONUT (5-12) groups. RESULTS: In total, 1079 participants were recruited, comprising 288 controls and 791 AIS patients. Among the 791 patients, 64 (8.1%) had malnutrition and 63 (7.9%) had an in-hospital death. Compared to the controls, the AIS patients presented higher CONUT scores, higher proportion of in-hospital mortality (8.0%), and longer length of stay. Malnutrition was independently associated with in-hospital mortality in the AIS patients (adjusted odds ratio: 3.77, 95% confidence interval [CI]: 1.55-9.15; p = 0.003). The general linear models showed an association between the CONUT score and LOS (ß = 0.574, 95% CI: 0.208-0.934; p = 0.002). Furthermore, the effect of the interaction between infection and nutrition status on in-hospital mortality showed borderline statistical significance (p = 0.06). CONCLUSIONS: Malnutrition estimated by the CONUT score on admission can be a predictor of in-hospital mortality and increased LOS in elderly AIS patients.

Expression of miR-210, miR-137, and miR-153 in Patients with Acute Cerebral Infarction.

AIM: To explore the expression levels of miR-210, miR-137, and miR-153 in patients with acute cerebral infarction. Material and Methods. 76 patients with acute cerebral infarction treated in our hospital from April 2016 to October 2017 were enrolled as the observation group. Another 64 normal patients were selected as the control group. The patients were divided into the death and survival groups based on 1-year mortality of patients. qRT-PCR was used to detect the expression of miR-210, miR-137, and miR-153 in the serum of each group. Receiver operating characteristic (ROC) curve was employed to analyze the diagnostic value and predictive value of miR-210, miR-137 and miR-153 death in patients. The correlation between miR-210, miR-137, and miR-153 in the serum of the observation group was analyzed by Pearson's test. RESULTS: Levels of miR-210 and miR-137 in the observation group were significantly lower than those in the control group, while levels of miR-153 in the observation group were significantly higher than those in the control group (all P < 0.05). The ROC curve of diagnosis of acute cerebral infarction showed that the area under curve of miR-210 was 0.836, that of miR-137 was 0.843, and that of miR-153 was 0.842. The 1-year survival rate was 71.05%. The 1-year survival of the low-expression group of miR-210 and miR-137 was significantly lower than that of the high-expression group, while the 1-year survival of the low-expression group of miR-153 was significantly higher than that of the high-expression group (all P < 0.05). The ROC curve for predicting death showed that the area under curve of miR-210 was 0.786, that of miR-137 was 0.824, and that of miR-153 was 0.858. Pearson's correlation analysis showed that the expression of miR-210 was positively correlated with that of miR-137, while miR-137 was negatively correlated with that of miR-153 and miR-210 was negatively correlated with that of miR-153. CONCLUSION: miR-210, miR-137, and miR-153 have a certain value in the diagnosis and prediction of 1-year death of acute cerebral infarction and may be potential diagnostic and predictive indicators.

Short- and long-term mortality after intravenous thrombolysis for acute ischemic stroke: A propensity score-matched cohort with 5-year follow-up.

ABSTRACT: It remains unknown whether intravenous thrombolysis (IVT), thrombectomy, or poststroke antithrombotic medication lower short- and long-term mortality in acute ischemic stroke (AIS). This study aimed to investigate the efficacy of IVT in AIS using propensity score matching, to determine whether IVT could reduce short- and long-term mortality, and to identify risk factors influencing short- and long-term mortality in AIS.During 2013 to 2014, the nationwide Korea Acute Stroke Assessment registry enrolled 14,394 patients with first-ever recorded ischemic stroke. Propensity score matching was used to match IVT and control cases with a 1:1 ratio. The primary outcome was survival up to 3 months, 1 year, and 5 years, as assessed using Kaplan-Meier estimates and Cox proportional hazards.In total, 1317 patients treated with IVT were matched with 1317 patients not treated with IVT. Survival was higher in the IVT group (median, 3.53 years) than in the non-IVT group (median, 3.37 years, stratified log-rank test, P < .001). Compared with the non-IVT group, thrombolysis performed within 2 hours significantly reduced the risk of 3-month mortality by 37%, and thrombolysis performed between 2 and 4.5 hours significantly reduced the risk of 3-month mortality by 26%. Thrombectomy significantly reduced the risk of 3-month mortality by 28%. Compared with no poststroke medication, poststroke antiplatelet medication was associated with 51%, 55%, and 52% decreases in 3-month, 1-year, and 5-year mortality risk, respectively. Poststroke anticoagulant medication was associated with 51%, 54%, and 44% decreases in the risk of 3-month, 1-year, and 5-year mortality, respectively.IVT and mechanical thrombectomy showed improvement in short-term survival. To improve long-term outcomes, the use of poststroke antithrombotic medication is important in AIS.

Exercise-Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression.

Irisin, which can be released in the hippocampus after physical exercise, is demonstrated to have beneficial effects on neurovascular diseases. This study investigated the impact of exercise linked-irisin on mortality and cognition in a mice model of cerebral ischemia and further explored its underlying mechanism. The cerebrospinal concentrations of irisin and klotho from ischemic stroke patients were measured with an enzyme-linked immunosorbent assay (ELISA). The cognitive function of mice was evaluated by a series of behavioural experiments. The expressions of klotho, MnSOD, and FOXO3a in the hippocampus of mice were detected by Western blot. Superoxide production in the brain tissue of mice was evaluated with the dihydroethidium (DHE) dying. The results demonstrated that stroke patients showed a positive correlation between their CSF irisin concentration and klotho concentration. In addition, when mice subjected to cerebral ischemia, their cognitive function was impaired, the protein expressions of klotho, MnSOD, and FOXO3a downregulated, and the production of reactive oxygen species (ROS) increased compared with the sham group. After pretreatment with exogenous irisin, improved cognitive impairment, upregulated protein expressions of klotho, MnSOD, and FOXO3a, and reduced ROS generation were observed in mice with MCAO. However, the neuroprotective effects of irisin compromised with the evidence of severe cognitive impairment, decreased protein expressions of MnSOD and FOXO3a, and increased ROS production in klotho knockout mice. Thus, our results indicated that exercise-linked irisin could prevent mortality and improve cognitive impairment after cerebral ischemia by regulating klotho expression.

Deintensification or No Statin Treatment Is Associated With Higher Mortality in Patients With Ischemic Stroke or Transient Ischemic Attack.

Background and Purpose: Practice guidelines recommend that most patients receive moderate- or high-potency statins after ischemic stroke or transient ischemic attack (TIA) of atherosclerotic origin. We tested the association of different patterns of potency for prescribed statin therapy­assessed before admission and at hospital discharge for ischemic stroke or TIA­on mortality in a large, nationwide sample of US Veterans. Methods: The study population included patients with an ischemic stroke or TIA occurring during 2011 at any of the 134 Veterans Health Administration facilities. We used electronic outpatient pharmacy files to identify statin dose at hospital admission and within 7 days after hospital discharge. We categorized statin dosing as low, moderate, or high potency; moderate or high potency was considered at goal. We created 6 mutually exclusive groups to reflect patterns of statin potency from hospital admission to discharge: goal to goal, low to goal, goal to low or goal to none (deintensification), none to none, none to low, and low to low. We used logistic regression to compare 30-day and 1-year mortality across statin potency groups. Results: The population included 9380 predominately White (71.1%) men (96.3%) who were hospitalized for stroke or TIA. In this sample, 34.1% of patients (n=3194) were discharged off a statin medication. Deintensification occurred in 14.0% of patients (n=1312) and none to none in 20.5% (n=1924). Deintensification and none to none were associated with a higher odds of mortality as compared with goal to goal (adjusted odds ratio 1-year mortality: deintensification versus goal to goal, 1.26 [95% CI, 1.02­1.57]; none to none versus goal to goal, 1.59 [95% CI, 1.30­1.93]). Adjustments for differences in baseline characteristics using propensity weighted scores demonstrated similar results. Conclusions: Underutilization of statins, including no treatment or underdosing after stroke (deintensification), was observed in approximately one-third of veterans with ischemic stroke or TIA and was associated with higher mortality when compared with patients who were at goal for statin prescription dosing.

The relationship of vitamin D deficiency with severity and outcome of acute stroke.

Background. There are currently conflicting results regarding the link between vitamin D deficiency and the increased risk for stroke and its poor prognosis. The present study aimed to assess the relationship between vitamin D deficiency and prognosis of acute stroke. Methods. This bi-center cross-sectional study was performed on 140 consecutive patients who referred to two general hospitals in Iran with the diagnosis of acute stroke. The levels of 25-hydroxy vitamin D were evaluated by Electrochemiluminescence (ECL) technique. Clinical severity of stroke on admission as well as on discharge time were evaluated using the National Institutes of Health Stroke Scale (NIHSS) or Modified Rankin (mRS) tools. Results. Mean serum level of vitamin D was 25.51 ± 18.87 ng/mL, ranging from 3.0 to 98.6 ng/ml. There was a significant difference between the two groups (with and without vitamin D deficiency) in terms of stroke severity and disability, as reflected by mRS (P=0.003) and NIHSS evaluation (14.24 ± 9.23 versus 9.73 ± 7.36, P=0.003). Also, regarding patients' clinical condition, the mean NIHSS score in those with deficient and normal levels of vitamin D was 14.24 ± 9.23 and 9.73 ± 7.36, respectively with NIHSS score > 5 in 76.1% and 61.5%, respectively (P = 0.003). Conclusion. According to the results of study, vitamin D status can be related to the severity of stroke. However, considering the cross-sectional design of our study, it could not point out the causality between vitamin D deficiency and acute stroke and further studies are warranted. It is not possible to draw any conclusions in terms of causality. Further studies are required in order to assess the relationship between the serum vitamin D levels and stroke severity.

Involvement of emergency medicine pharmacists in stroke thrombolysis: A cohort study.

WHAT IS KNOWN AND OBJECTIVE: Thrombolysis with Alteplase (rtPA) improves functional outcome among selected patients after acute ischaemic stroke. Benefits are most pronounced with early intervention. Our aim is to assess door to needle time (DTNT) for acute stroke after a stroke call-out redesign including addition of an emergency medicine (EM) pharmacist to the team. METHODS: A retrospective cohort of stroke patients who received rtPA was compared to a prospective cohort after stroke callout re-design in an adult major referral hospital in metropolitan Melbourne, Australia. All patients who presented during EM pharmacist working hours and were thrombolysed in the ED for stroke from December 2011-June 2014 pre and July 1st 2014-August 2019 post were included. The primary outcome was DTNT. Secondary outcomes included proportion of patients with a DTNT within 60 min, time to blood pressure (SBP) reduction, intracranial and extracranial bleeding, hospital length of stay (LOS) and mortality. RESULTS AND DISCUSSION: There were 218 patients eligible, 64 patients pre and 122 patients post implementation were included. The cohorts were similar in demographics. There was a significant association of time to thrombolysis (HR 1.61; 95% CI: 1.18-2.20; p = 0.003) with the intervention. Median DTNT improved from 73 (IQR 52-111) min to 61 (IQR 47-80) min (p = 0.012). Interrupted time-series analysis did not demonstrate intervention at the single time-point of implementation of the intervention to be associated with the improvement. WHAT IS NEW AND CONCLUSION: Re-design of the stroke call-out team that included addition of an EM pharmacist was associated with improvements in DTNT. The effect of individual interventions at one point in time could not be demonstrated.

Association of White Matter Hyperintensity Markers on MRI and Long-term Risk of Mortality and Ischemic Stroke: The SMART-MR Study.

OBJECTIVE: To determine whether white matter hyperintensity (WMH) markers on MRI are associated with long-term risk of mortality and ischemic stroke. METHODS: We included consecutive patients with manifest arterial disease enrolled in the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study. We obtained WMH markers (volume, type, and shape) from brain MRI scans performed at baseline using an automated algorithm. During follow-up, occurrence of death and ischemic stroke was recorded. Using Cox regression, we investigated associations of WMH markers with risk of mortality and ischemic stroke, adjusting for demographics, cardiovascular risk factors, and cerebrovascular disease. RESULTS: We included 999 patients (59 ± 10 years; 79% male) with a median follow-up of 12.5 years (range 0.2-16.0 years). A greater periventricular or confluent WMH volume was independently associated with a greater risk of vascular death (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13-1.47) for a 1-unit increase in natural log-transformed WMH volume and ischemic stroke (HR 1.53, 95% CI 1.26-1.86). A confluent WMH type was independently associated with a greater risk of vascular (HR 1.89, 95% CI 1.15-3.11) and nonvascular death (HR 1.65, 95% CI 1.01-2.73) and ischemic stroke (HR 2.83, 95% CI 1.36-5.87). A more irregular shape of periventricular or confluent WMH, as expressed by an increase in concavity index, was independently associated with a greater risk of vascular (HR 1.20, 95% CI 1.05-1.38 per SD increase) and nonvascular death (HR 1.21, 95% CI 1.03-1.42) and ischemic stroke (HR 1.28, 95% CI 1.05-1.55). CONCLUSIONS: WMH volume, type, and shape are associated with long-term risk of mortality and ischemic stroke in patients with manifest arterial disease.

Higher Mortality of Ischaemic Stroke Patients Hospitalized with COVID-19 Compared to Historical Controls.

INTRODUCTION: Increasing evidence suggests patients with coronavirus disease 2019 (COVID-19) may develop thrombosis and thrombosis-related complications. Some previous evidence has suggested COVID-19-associated strokes are more severe with worse outcomes for patients, but further studies are needed to confirm these findings. The aim of this study was to determine the association between COVID-19 and mortality for patients with ischaemic stroke in a large multicentre study. METHODS: A retrospective cohort study was conducted using electronic medical records of inpatients from 50 healthcare organizations, predominately from the USA. Patients with ischaemic stroke within 30 days of COVID-19 were identified. COVID-19 was determined from diagnosis codes or a positive test result identified with CO-VID-19-specific laboratory codes between January 20, 2020, and October 1, 2020. Historical controls with ischaemic stroke without COVID-19 were identified in the period January 20, 2019, to October 1, 2019. 1:1 propensity score matching was used to balance the cohorts with and without CO-VID-19 on characteristics including age, sex, race and comorbidities. Kaplan-Meier survival curves for all-cause 60-day mortality by COVID-19 status were produced. RESULTS: During the study period, there were 954 inpatients with ischaemic stroke and COVID-19. During the same time period in 2019, there were 48,363 inpatients with ischaemic stroke without COVID-19 (historical controls). Compared to patients with ischaemic stroke without COVID-19, patients with ischaemic stroke and COVID-19 had a lower mean age, had a lower prevalence of white patients, a higher prevalence of black or African American patients and a higher prevalence of hypertension, previous cerebrovascular disease, diabetes mellitus, ischaemic heart disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, liver disease, neoplasms, and mental disorders due to known physiological conditions. After propensity score matching, there were 952 cases and 952 historical controls; cases and historical controls were better balanced on all included characteristics (all p > 0.05). After propensity score matching, Kaplan-Meier survival analysis showed the survival probability was significantly lower in ischaemic stroke patients with COVID-19 (78.3% vs. 91.0%, log-rank test p < 0.0001). The odds of 60-day mortality were significantly higher for patients with ischaemic stroke and COVID-19 compared to the propensity score-matched historical controls (odds ratio: 2.51 [95% confidence interval 1.88-3.34]). DISCUSSION/CONCLUSIONS: Ischaemic stroke patients with COVID-19 had significantly higher 60-day all-cause mortality compared to propensity score-matched historical controls (ischaemic stroke patients without COVID-19).