Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy.

BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment within 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered within 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial.

BACKGROUND: There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients. METHODS: In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic stroke who were eligible for standard intravenous thrombolysis but ineligible for endovascular thrombectomy were enrolled from 53 centres in China and randomly assigned (1:1) to receive intravenous tenecteplase (0·25 mg/kg, maximum dose of 25 mg) or intravenous alteplase (0·9 mg/kg, maximum dose of 90 mg). Participants had to be able to receive treatment within 4·5 h of stroke, have a modified Rankin Scale (mRS) score of no more than 1 before enrolment, and have a National Institutes of Health Stroke Scale score of 5-25. Patients and treating clinicians were not masked to group assignment; clinicians evaluating outcomes were masked to treatment type. The primary efficacy outcome was the proportion of participants who had a mRS score of 0-1 at 90 days, assessed in the modified intention-to-treat population (all randomly assigned participants who received the allocated thrombolytic), with a non-inferiority margin of 0·937 for the risk ratio (RR). The primary safety outcome was symptomatic intracranial haemorrhage within 36 h, assessed in all participants who received study drug and had a safety assessment available. The trial is registered with ClinicalTrials.gov, NCT04797013, and has been completed. FINDINGS: Between June 12, 2021, and May 29, 2022, 1430 participants were enrolled and randomly assigned to tenecteplase (n=716) or alteplase (n=714). Six patients assigned to tenecteplase and seven to alteplase did not receive study product, and five participants in the tenecteplase group and 11 in the alteplase group were lost to follow-up at 90 days. The primary outcome in the modified intention-to-treat population occurred in 439 (62%) of 705 in the tenecteplase group versus 405 (58%) of 696 in the alteplase group (RR 1·07, 95% CI 0·98-1·16). The lower limit of the RR's 95% CI was greater than the non-inferiority margin. Symptomatic intracranial haemorrhage within 36 h was observed in 15 (2%) of 711 in the tenecteplase group and 13 (2%) of 706 in the alteplase group (RR 1·18, 95% CI 0·56-2·50). Mortality within 90 days occurred in 46 (7%) individuals in the tenecteplase group versus 35 (5%) in the alteplase group (RR 1·31, 95% CI 0·86-2·01). INTERPRETATION: Tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy. FUNDING: National Science and Technology Major Project, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

Advances in Acute Ischemic Stroke Therapy.

The treatment of acute ischemic stroke continues to advance. The mainstay of treatment remains intravenous thrombolysis with alteplase. Recent studies demonstrated that later treatment with alteplase is beneficial in patients selected with advanced imaging techniques. Tenecteplase has been evaluated as an alternative thrombolytic drug and evidence suggests that it is as least as effective as alteplase and may lyse large vessel clots more effectively. Endovascular therapy with mechanical thrombectomy has now been shown to be beneficial up to 24 hours after stroke onset in carefully selected patients with proximal, large vessel occlusions. Ongoing studies are evaluating the effectiveness of thrombectomy in patients with more distal vessel occlusions and patients with proximal large vessel occlusions with larger ischemic core volumes and also in patients with milder neurological deficits. Cytoprotection is another potential acute stroke therapy that has not demonstrated efficacy in prior clinical trials. It should be reconsidered as an adjunct to reperfusion and a variety of new clinical trials can be envisioned to evaluate the potential benefits of cytoprotection in patients before and after reperfusion.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

Clinical significance of the Microbleed Anatomical Rating Scale score in ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: Conflicting results were shown on the relationship between cerebral microbleeds (CMBs) burden and functional outcomes in patients treated with intravenous tissues plasminogen activator (IV tPA). We aimed to investigate the relationship between CMBs burden and functional outcomes using the Microbleed Anatomical Rating Scale (MARS) and determine its optimal cutoff value. METHODS: A retrospective study was conducted to include patients treated with IV tPA in our stroke center, and the MARS was used to assess the CMBs burden. Other clinical data including demographic factors, stroke severity, vascular risk factors, and clinical outcomes were also documented. Another mediation analysis was performed to investigate whether early neurological improvement could mediate the association between MARS and functional outcomes. RESULTS: A total of 408 patients were included. A cutoff value of 1.5 could predict functional outcomes in patients treated with IV tPA. Based on that cutoff value, MARS showed an independent relationship with functional outcomes [adjusted OR (Odds Ratio) 0.841, 95% confidence interval (CI) 0.720-0.982, P = .029]. A shift analysis showed that higher MARS score (MARS ≥1.5) was related with poor functional outcome according to mRS score distribution (OR = 0.519, 95% CI 0.336-0.803, P = .003). Total effect (indirect + direct effect) was calculated and showed in figure. Early neurological improvement mediated 24% of the effect of MARS score on functional outcomes. CONCLUSION: Our study showed that MARS could be a potential method to assess the functional outcome based on CMBs in patients treated with IV tPA, and MARS score ≥ 1.5 might be an optimal threshold for poor functional outcome.

Risk factors and Outcomes of Dysphagia Among Patients Hospitalized with Acute Intracerebral Hemorrhage: Findings from the Chinese Stroke Center Alliance.

Objective: Dysphagia is a common and severe symptom of acute stroke; however, few studies investigated the prevalence of and risk factors of dysphagia among intracerebral hemorrhage (ICH) patients. We aimed to determine the prevalence and risk factors for dysphagia among acute ICH patients, and assess its impact on outcome of hospitalization. Methods: We collected data of ICH patients from the Chinese Stroke Center Alliance (CSCA) from August 2015 to July 2019 retrospectively. Univariate analysis and multivariable analysis were conducted to identify the factors associated with dysphagia and the outcomes of hospitalization. Results: 32 581 eligible ICH patients were included in the final analysis. According to the results of the swallowing function assessment, patients were divided into 24 084 (73.9%) non-dysphagia group and 8497 (26.1%) dysphagia group. Compared with the non-dysphagia group, the dysphagia group had poor outcomes, including higher incidence of pneumonia (60.2% vs 17.3%, OR 4.82, 95% CI 4.53-5.13) and in-hospital mortality (3.5% vs 0.3%, OR 5.96, 95% CI 4.41-8.06), longer length of stay (P < .01), higher hospitalization cost (P < .01), and higher medicine cost (P < .01). In multivariable analysis, the incidence of dysphagia was independently associated with older age (OR 1.10, 95% CI 1.09-1.11), male sex (OR 1.13, 95% CI 1.06-1.20), arrival at the hospital by emergency medical services (OR 2.11, 95% CI 1.99-2.24), lower Glasgow Coma Scale (GCS) score (per point decrease) (OR 0.78, 95% CI 0.77-0.78), history of ICH (OR 1.25, 95% CI 1.17-1.35), and higher glucose level (OR 1.09, 95% CI 1.07-1.10). Conclusions: More than one-quarter of acute ICH patients were diagnosed with dysphagia, which was associated with poor hospital outcomes. The early identification and management of dysphagia may reduce the possibility of stroke-associated pheumonia, shorten the length of hospital stay, and reduce medical cost.

Insulin resistance estimated by estimated glucose disposal rate predicts outcomes in acute ischemic stroke patients.

BACKGROUND: Estimated glucose disposal rate (eGDR), a simple and noninvasive measure of insulin resistance, has been proven to be an independent risk factor for first-time stroke and all-cause mortality. In this study, we aimed to investigate the associations between eGDR and the stroke outcome in patients with first-time acute ischemic stroke (AIS). METHODS: We included first-time AIS patients with available data on eGDR in the China National Stroke Registry III (CNSR-III), and divided the subjects into lower eGDR group (eGDR ≤ 6 mg/kg/min) and higher eGDR group (eGDR > 6 mg/kg/min). The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1) at 3 months. Secondary outcomes included stroke recurrence and favorable functional outcome (modified Rankin Scale score 0-2) at 3 months, and functional outcome and combined vascular event at one year. Univariate and multivariate analyses were performed to evaluate the association between eGDR and outcomes. RESULTS: A total of 6,271 patients with AIS were included in this study. The median values of eGDR in lower and higher eGDR group were 5.0 mg/kg/min (interquartile range, 4.2-5.6) and 7.6 mg/kg/min (interquartile range, 6.8-9.6), respectively. Patients with higher eGDR were significantly associated with higher incidence of excellent functional outcome (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.45; P < 0.01) at 3 months and favorable (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.93; P < 0.01) and excellent (adjusted odds ratio, 1.28; 95% confidence interval, 1.08-1.51; P < 0.01) functional outcome at one year. However, there was no significant difference in stroke recurrence between these two groups at 3 months (adjusted odds ratio, 0.81; 95% confidence interval, 0.61-1.06; P = 0.12) and one year (adjusted odds ratio, 0.91; 95% confidence interval, 0.73-1.14; P = 0.41). CONCLUSION: eGDR is a predictor of functional outcome in patients with AIS, independent of traditional cardiovascular predictors.

Treatment strategies and prognosis for moderate stroke patients in China.

INTRODUCTION: Moderate stroke patients with National Institutes of Health Stroke Scale (NIHSS) score of 4-10 and without intravenous thrombolysis or endovascular treatment are basically excluded from current secondary prevention trials. We aimed to explore the effectiveness of mono- vs. dual-antiplatelet (DAPT) treatment strategies against subsequent stroke for these patients in a nationwide cohort. METHODS: Data were derived from the Third China National Stroke Registry (CNSR-Ш). In this prospective nationwide cohort, moderate ischemic stroke patients with NIHSS 4-10 and without intravenous thrombolysis or endovascular treatment were included and categorized into mono- or dual-antiplatelet groups. Demographics, medical history, NIHSS score, imaging and laboratory data were collected. The outcomes were stroke recurrence and all-cause mortality at 3 months and at 1 year, respectively. Cox proportional-hazards models were utilized to investigate the association of treatment strategies and prognosis. RESULTS: Of a total of 2 414 patients enrolled in the study, 1 633 (67.6%) received clopidogrel or aspirin and 781 (32.4%) received DAPT. Recurrent stroke occurred in 108 (6.6%) patients of the mono-antiplatelt group and 40 (5.1%) patients of the DAPT group ( adjusted hazard ratio [aHR] 0.73, 95% confidential interval [CI] 0.47-1.13, P=0.16) at 3 months, and the rate of stroke recurrence was 10.7% in the mono-antiplatelet group and 8.6% in the DAPT group ( aHR 0.81, 95% CI 0.58-1.13, P=0.22) at 12 months. The DAPT paradigm was not significantly associated with death at 3 months (0.6% vs 0.3%, a HR 0.28, 95%CI 0.04-2.25) but significantly reduced the mortality at 12 months (2.3% vs 1.0%, aHR 0.41, 95% CI 0.17-0.98, P=0.046). CONCLUSIONS: In moderate stroke patients presenting within 24 hours of symptom onset, the addition of clopidogrel 75 mg to aspirin might not be associated with lower risk of recurrent stroke than aspirin or clopidogrel alone.

Intravenous thrombolysis for acute ischemic stroke during two COVID-19 outbreaks in China: Wuhan pandemic and Beijing pandemic.

INTRODUCTION: The COVID-19 pandemic has had an impact on the emergency department (ED). Door-to-needle time (DNT) could be prolonged for intravenous thrombolysis (IVT) treatment. We aimed to investigate the impact of two COVID-19 pandemics on the workflow of IVT in our neurovascular ED. METHOD: We performed a retrospective analysis of patients who received IVT treatment in the neurovascular ED of Beijing Tiantan Hospital, Beijing, from January 20, 2020, to October 30, 2020, covering two COVID-19 pandemics in China. The time-based performances of IVT treatment including onset-to-arrival time, arrival-to-CT time, CT-to-needle time, door-to-needle time, and onset-to-needle time were recorded. Data on clinical characteristics and imaging information were also collected. RESULTS: Four hundred forty patients that received IVT were enrolled in this study. The number of patients admitted to our neurovascular ED began to decrease in December 2019 and was the lowest in April 2020 (n = 95). Longer DNT (Wuhan pandemic: 49.00 [35.00, 64.00] min; Beijing pandemic: 55.00 [45.50, 77.00] min) interval delays were observed during the two pandemics (p = .016). More patients admitted during the two pandemics had an 'unknown' subtype (Wuhan pandemic: 21.8%; Beijing pandemic: 31.4%. p = .008). The percentage of the cardiac embolism subtype was higher during the Wuhan pandemic (20.0%) than during other periods. The median admission NIHSS score increased during the Wuhan pandemic and the Beijing pandemic (8.00 [4.00, 12.00], 7.00 [4.50, 14.00], respectively, p < .001). CONCLUSION: The number of patients who received IVT decreased during the Wuhan pandemic. Higher admission NIHSS scores and prolonged DNT intervals were also observed during the Wuhan pandemic and the Beijing pandemic.

What predicts large vessel occlusion in mild stroke patients?

BACKGROUND AND PURPOSE: Mild acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) may benefit from thrombolysis or thrombectomy therapy. However, the predictors for LVO in mild AIS patients have not been extensively explored. We aimed to investigate the predictors for LVO in mild AIS patients. METHODS: We collected the data of consecutive AIS patients with a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 from The Third China National Stroke Registry - a prospective nationwide registry of AIS or transient ischemic attack (TIA) patients in China from August 2015 to March 2018. Patients were divided into LVO and non-LVO group based on the vascular imaging during the hospitalization. Multivariable regression analyses involving clinical characteristics and NIHSS subitems was performed to detect the predictors for LVO. RESULT: A total of 7653 mild AIS patients from The Third China National Stroke Registry were included in this study. Among them, 620 patients (8.1%) had LVO. The level of consciousness (adjusted odds ratio, 1.87; 95% confidence interval, 1.08 to 3.23), visual field (adjusted odds ratio, 2.10; 95% confidence interval, 1.43 to 3.06) and sensory (adjusted odds ratio, 0.75; 95% confidence interval, 0.60 to 0.94) were predictors for mild AIS patients with LVO. CONCLUSIONS: Impaired LOC, visual field and sensory were independently predictors for LVO in mild stroke patients. Further studies are warranted to test these predictors in prehospital setting and in other population.

Short- and long-term outcomes of patients with minor stroke and nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: Nonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event. METHODS: Data were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes. RESULTS: A total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P < 0.001) and multivariate analyses (HR, 4.66; 95% CI, 1.79 to 12.15; P = 0.001). There was no difference in the in-hospital ischemic stroke recurrence rate between the two groups (HR, 0.45 [95% CI, 0.19 to 1.05] P = 0.07 at discharge). However, patients with NVAF had a lower rate of recurrent ischemic stroke at medium- (3 months and 6 months) and long-term (12 months) follow-up (HR, 0.33 [95% CI, 0.16 to 0.68] P = 0.003 at 3 months; 0.49 [95% CI, 0.27 to 0.89] P = 0.02 at 6 months; 0.55 [95% CI, 0.32 to 0.94] P = 0.03 at 12 months, respectively) compared with those without. There was no difference in all-cause mortality and hemorrhagic stroke between the two groups during follow-up. CONCLUSIONS: Minor stroke patients with NVAF were at higher risk of cardiovascular death but had a lower rate of recurrent ischemic stroke compared to those without during the subsequent year after stroke event. A more accurate stroke risk prediction model for NVAF is warranted for optimal patient care strategies.

Advances in Futile Reperfusion following Endovascular Treatment in Acute Ischemic Stroke due to Large Vessel Occlusion.

BACKGROUND: Futile reperfusion (FR) is becoming an urgent issue for acute ischemic stroke patients who underwent endovascular treatment (EVT). Although the recanalization rate has improved after EVT, it is far from translating to increased tissue reperfusion and functional independence. SUMMARY: Many underlying mechanisms including the "no-reflow" phenomenon, poor collateral flow, venous dysfunction, and inflammation were proposed, but the pathophysiology of FR is still unclear. Clinically, reliable predictors are still yet to be identified, and ongoing trials on shortening the time delay and cytoprotection may provide novel ideas for interventions of FR. KEY MESSAGES: This review will summarize the latest advances in FR and hopefully shed light on potential interventions.

Intravenous thrombolysis for mild stroke: NIHSS 3-5 Versus NIHSS 0-2.

BACKGROUND AND PURPOSE: Studies have shown that mild stroke patients with National Institutes of Health Stroke Scale (NIHSS) score 3-5 but not 0-2 may benefit from the intravenous thrombolysis when compared with antiplatelet therapy. We aimed to compare the safety and effectiveness of thrombolysis in mild stroke with NIHSS score of 0-2 vs. 3-5 and identify the predictors of an excellent functional outcome in a real world longitudinal registry. METHODS: In a prospective thrombolysis registry, we identified patients with acute ischemic stroke who presented within 4.5 hours of symptom onset and had initial NIHSS scores ≤ 5. Demographic data, medical history, pre-stroke medications, imaging data, and laboratory measures were collected. The outcome of interest was modified Rankin Scale score of 0 to 1 at discharge. Safety outcome was evaluated by syptomatic intracrerebral hemorrhage defined as any decline in neurologic status due to hemorrhage within 36 h. Multivariable regression models were performed to explore the safety and effectiveness in the alteplase-treated patients with admission NIHSS 0-2 vs. 3-5 and identify factors independently associated with an excellent functional outcome. RESULTS: Of a total of 236 eligible patients, those with an admission NIHSS score of 0-2 (n=80) had a better functional outcome at discharge compared with NIHSS 3-5 group (n=156) (81.3% vs. 48.7%, adjusted odds ratio [aOR] 0.40, 95% confidential interval [CI] 0.17 - 0.94, P=0.04) without increasing the rate of symptomatic intracerebral hemorrhage and mortality. Non-disabling stroke (Model 1: aOR 0.06, 95%CI 0.01-0.50, P=0.01; Model 2: aOR 0.06, 95% CI 0.01-0.48, P=0.01) and prior statin therapy (Model 1: aOR 3.46, 95% CI 1.02-11.70, P=0.046; Model 2: aOR 3.30, 95% CI 0.96-11.30, P=0.06) were independent predictors of excellent outcomes. CONCLUSIONS: Acute ischemic stroke patients with admission NIHSS 0-2 was associated with better functional outcomes at discharge compared with NIHSS 3-5 within the 4.5-hour time window. Minor stroke severity, non-disabling stroke and prior statin therapy were independent predictors for funcitonal outcomes at discharge. Further studies with large sample size are needed to confirm the findings.

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

BACKGROUND: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study. METHODS: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups. RESULTS: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P<0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment. CONCLUSIONS: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Prognostic value of glycemic gap in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Glycemic gap (GG), as a novel biomarker showing the acute glycemic change after the onset of acute illness, has been found to be associated with adverse outcomes in many diseases. This study aimed to explore the prognostic value of GG on long-term outcomes of spontaneous intracerebral hemorrhage (sICH). METHODS: The current study included 528 patients from a multicenter, prospective, consecutive, observational cohort study. Poor clinical outcome was defined as modified Rankin Scale ≥ 3. GG was calculated using admission blood glucose minus hemoglobin A1c-derived average blood glucose. Logistic regression analyses were performed to determine the association between GG and poor clinical outcomes at 30 days, 90 days, and 1 year. RESULTS: Glycemic gap was significantly associated with poor clinical outcomes at 30 days, 90 days, and 1 year (p < 0.05 for all models), where patients with higher GG were more likely to have poor clinical outcome. Restricted cubic splines revealed a positive association between GG and poor clinical outcome. In addition, patients with higher GG were more likely to have a higher 1-year mortality rate. The addition of GG to the intracerebral hemorrhage score improved the discrimination and calibration properties for the prediction of poor clinical outcome. CONCLUSIONS: Glycemic gap was independently associated with poor outcomes and may be a valuable prognostic factor in patients with sICH.

In-hospital clinical outcomes in diffusion weighted imaging-negative stroke treated with intravenous thrombolysis.

OBJECTIVE: We aimed to investigate whether negative diffusion weighted imaging (DWI) is related to the in-hospital clinical outcomes for ischemic stroke patients with intravenous tissues plasminogen activator (IV tPA). METHODS: We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. The classification of DWI-positive or negative was based on post-IV tPA MR scan. Demographic factors, stroke characteristics, imaging information, and the in-hospital clinical outcomes including early neurological improvement (ENI) and favourable functional outcome were collected. Multivariable logistic regression and sensitivity analyses were conducted to test whether negative DWI imaging was an independent predictor of the in-hospital clinical outcomes. RESULTS: In the final study population, 437 patients treated with IV tPA were included and 12.36% of them had negative DWI imaging at the first MR scan post IV tPA. In the DWI-negative group, 51.9% (28/54) of the patients achieved ENI at 24 hours and 74.1% (40/54) of the patients achieved favourable clinical outcome at discharge. DWI-negative was not related to ENI (adjusted odds ratio 0.93, 95% confidence interval 0.17-4.91) or favourable clinical outcome (adjusted odds ratio 2.40, 95% confidence interval 0.48-11.95). Additional sensitivity analyses yielded similar results. CONCLUSION: DWI-negative is not associated with ENI or favourable functional outcome at discharge.

P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack.

BACKGROUND AND PURPOSE: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack. METHODS: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I2 test. RESULTS: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68-0.83], I2=0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90-1.89], I2=0%), cardiovascular death (RR, 1.34 [95% CI, 0.56-3.17], I2=0%), mild bleeding (RR, 1.25 [95% CI, 0.37-4.29], I2=94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62-3.39], I2=0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16-4.08], I2=41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75-4.67], I2=0%) or ticagrelor (RR, 2.17 [95% CI, 1.16-4.08], I2=37%) but not within 21 days or clopidogrel. CONCLUSIONS: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.

Clinical Characteristics and In-Hospital Outcomes of Varying Definitions of Minor Stroke: From a Large-Scale Nation-Wide Longitudinal Registry.

BACKGROUND AND PURPOSE: A variety of definitions for minor stroke have been proposed. We aimed to compare the clinical characteristics and outcomes of minor stroke defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 versus ≤3. METHODS: We retrieved acute ischemic stroke patients with NIHSS score ≤5 in the CSCA study (China Stroke Center Alliance) between August 2015 and 2019. In-hospital clinical outcomes including all-cause mortality, stroke, and myocardial infarction were compared between the NIHSS score ≤5 and NIHSS score ≤3 groups using absolute standardized differences (ASD). RESULTS: A total of 1 006 798 patients were registered in the CSCA program from 1476 hospitals, 472 352 patients had NIHSS score ≤5, of whom 356 314 patients had NIHSS score ≤3. The in-hospital composite events of death, myocardial infarction, or recurrent stroke were not significantly different between the NIHSS score ≤5 and NIHSS score ≤3 groups (5.6% [26 346/472 352] versus 5.2% [18 682/356 314]; ASD, 1.8). The in-hospital all-cause mortality (0.1% [443/472 352] versus 0.1% [255/356 314]; ASD, <0.01), recurrent ischemic stroke (5.3% [25 026/472 352] versus 5.0% [17 777/356 314]; ASD, 1.4), and hemorrhagic stroke (0.5% [2151/472 352] versus 0.4% [1475/356 314]; ASD, 1.5) were not significantly different between both the NIHSS score ≤5 and NIHSS score ≤3 groups. CONCLUSIONS: Our large-scale study identified that minor stroke using NIHSS scores ≤5 and ≤3 as the definition was comparable with each other regarding in-hospital all-cause mortality, recurrent stroke, and hemorrhagic stroke. This observation may be useful for future comparison studies and clinical trial design.

Impacts of in-hospital workflow on functional outcome in stroke patients treated with endovascular thrombectomy.

High-performance in-hospital workflow may save time and improve the efficacy of thrombectomy in patients with acute ischemic stroke. However, the optimal in-hospital workflow is far from being formulated, and the current models varied distinctly among centers. This study aimed to evaluate the impacts of in-hospital workflow on functional outcomes after thrombectomy. Patients were enrolled from a multi-center registry program in China. Based on in-hospital managing procedure and personnel involved, two workflow models, neurologist-dominant and non-neurologist-dominant, were identified in the participating centers. Favorable outcome was defined as a mRS score of ≤ 2 at 90 days of stroke onset. After patients being matched with propensity score matching (PSM) method, ratios of favorable outcomes and symptomatic intracerebral hemorrhage (sICH) were compared between patients with different workflow models. Of the 632 enrolled patients, 543 (85.9%) were treated with neurologist-dominant and 89 (14.1%) with non-neurologist-dominant model. 88 patients with neurologist-dominant model and 88 patients with non-neurologist-dominant model were matched with PSM. For the matched patients, no significant differences concerning the ratios of successful recanalization (92.0% vs 87.5%, P = 0.45), sICH (17.0% vs 14.8%, P = 0.85), favorable outcome (42.0% vs 42.0%, P = 1.00) were detected between patients with neurologist-dominant model and those with non-neurologist-dominant model. Patients with neurologist-dominant model had shorter door to puncture time (124 (86-172) vs 156 (120-215), P = 0.005), fewer passes of retriever (2 (1-3) vs 2 (1-4), P = 0.04), lower rate of > 3 passes (11.4% vs 28.4%, P = 0.004), and lower incidence of asymptomatic intracerebral hemorrhage rate (27.3% vs 43.2%, P = 0.045). Although the neurologist-dominant model may decrease in-hospital delay and risk of asymptomatic intracerebral hemorrhage, workflow models may not influence the functional outcome significantly after thrombectomy in patients with acute ischemic stroke.

Brain Computed Tomography Angiography Maximum Intensity Projection Images for ASPECTS Derivation and Detection of Large Infarct Volumes: Preliminary Study.

PURPOSE: Non-contrast CT ASPECTS (NCCTasp) has an established role in determining eligibility for mechanical thrombectomy in centers without ready access to perfusion or DWI. Moreover, it has been suggested that CTA source ASPECTS (CTAasp) may be superior to NCCTasp in predicting final infarct volume (FIV). In this study, we hypothesized that CTA maximum intensity projection ASPECTS (MIPSasp) would be superior compared to both NCCTasp and CTAasp in predicting FIV as measured by DWI. MATERIALS AND METHODS: In 41 consecutive patients with MCA territory infarcts, NCCTasp, CTAasp and MIPSasp were visually assessed by 2 neuroradiologists. Disagreements were adjudicated by a third neuroradiologist, and the reconciled data used for all further analysis. MR-DWI was used as the standard for FIV determination. Receiver operating characteristic curve analysis was used to compare the area under the curve for all three CT-based methods in predicting FIV ≥70 ml. RESULTS: MIPSasp (AUC: 0.98, CI: 0.88-1.00) were statistically better than NCCTasp (AUC: 0.87, 95% CI: 0.72-0.95; p=0.01) in predicting FIV ≥70 ml. MIPSasp were also superior to CTAasp (AUC: 0.9, CI: 0.79-.98; p˂0.05). Optimal test performance for predicting FIV ≥70 ml for MIPSasp was ≤6 (sensitivity=100%, specificity=91.4%; Youden's J=0.98). CONCLUSION: Our preliminary study suggests that a novel CTA-MIPS derived ASPECTS better predicts large MCA territory infarcts compared to CTA source and non-contrast ASPECTS. Thus, MIPSasp may be a promising technique for future studies aimed at improving ischemic stroke treatment in centers using ASPECTS for stroke management.