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Background: NOD‑like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis is strongly related to cerebral ischemia/reperfusion (I/R) injury. DDX3X, the DEAD-box family's ATPase/RNA helicase, promotes NLRP3 inflammasome activation. However, whether DDX3X deficiency attenuates NLRP3 inflammasome-mediated pyroptosis induced by cerebral I/R injury. Objectives: This study investigated whether DDX3X deficiency attenuates NLRP3 inflammasome-mediated pyroptosis in N2a cells after oxygen-glucose deprivation/ reoxygenation (OGD/R) treatment. Methods: In vitro model of cerebral I/R injury, mouse neuro2a (N2a) cells subjected to OGD/R were treated with the knockdown of DDX3X. Cell counting kit-8 (CCK-8) assay and Lactate dehydrogenase (LDH) cytotoxicity assay were conducted to measure cell viability and membrane permeability. Double immunofluorescence was performed to determine the pyroptotic cells. Transmission electron microscopy (TEM) was used to observe morphological changes of pyroptosis. Pyroptosis-associated proteins were analyzed by Western blotting. Results: The OGD/R treatment reduced cell viability, increased pyroptotic cells and released LDH compared to the control group. TEM showed membrane pore formation of pyroptosis. Immunofluorescence showed that GSDMD was translocated from the cytoplasm to the membrane after OGD/R treatment. Western blotting showed that the expression of DDX3X, and pyroptosis-related proteins (NLRP3, cleaved-Caspase1, and GSDMD-N) were increased after OGD/R treatment. Nevertheless, DDX3X knockdown markedly improved cell viability and reduced LDH release, expression of pyroptosis-related proteins, and N2a cells pyroptosis. DDX3X knockdown significantly inhibited membrane pore formation and GSDMD translocation from cytoplasm to membrane. Conclusion: This research demonstrates for the first time that DDX3X knockdown attenuates OGD/R‑induced NLRP3 inflammasome activation and pyroptosis, which implies that DDX3X may become a potential therapeutic target for cerebral I/R injury.

Introduction: Efficacy and safety of tirofiban in endovascular therapy among cardio-embolized ischemic stroke patients remains controversial. We aimed to assess effects of tirofiban before endovascular therapy in cardio-embolized stroke patients. Methods: This is a post hoc analysis of Endovascular Treatment With vs Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial. Before endovascular therapy, participants were randomized to tirofiban or placebo group in ratio of 1:1. Tirofiban was administrated as a bolus dose of 10 ug/kg, followed by continuous infusion of 0.15 ug/kg /min for up to 24-hour. We collected cardio-embolized stroke patients according to Trial of Org 10172 in Acute Stroke Treatment classification. The efficacy outcome was global disability at 90-day assed by modified Rankin Scale (mRS). The primary safety outcome was symptomatic intracranial hemorrhage (sICH) assessed by Heidelberg bleeding classification within 48-hour. Secondary safety outcome was any radiologic intracranial hemorrhage and death at 90-day. Results: 406 cardio-embolized stroke patients were collected. Tirofiban did not correlated to favorable shift to lower 90-day mRS (adjusted odds ratio [aOR], 0.91; 95% CI, 0.64-1.3; P = 0.617). However, tirofiban subgroup had a significantly higher risk of sICH within 48-hour (aOR, 3.26; 95% CI, 1.4-7.57; P = 0.006) compared with placebo group. The aOR was 1.44 (95% CI, 0.94-2.19; P = 0.094) for any intracranial hemorrhage and 1.48 (95% CI, 0.88-2.52; P = 0.143) for death at 90-day. Conclusions: Tirofiban increased symptomatic intracranial hemorrhage after endovascular therapy in cardio-embolized stroke patients. Figure 1 . Outcomes of endovascular therapy in cardio-embolic stroke participants in tirofiban vs placebo group.

Yuan Yang,1,2 Ting Cui,1 Zuoxiao Li,2 Jinglun Li,2 Ting Duan,3 Zhengzhou Yuan,2 Changyi Wang,1 Jincheng Wan,1 Cao Li,4 Shujiang Zhang,2 Ling Li,2 Fayun Hu,1 Bo Wu1 1Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Bo Wu; Fayun Hu, Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel +86-18980602142 ; +86-15902861270, Email dr.bowu@hotmail.com; hufayun2006@163.comObjective: This study examined the functional outcomes and safety of endovascular treatment (EVT) in acute ischemic stroke (AIS) patients owing to large vessel occlusion of the anterior circulation, presented during a late-time window (6– 24 hours after last seen well (LSW)) in a real-world practice.Methods: This was a retrospective analysis from a bi-center prospective cohort. According to the stroke treatment, patients with continuous Alberta Stroke Plan Early Aspect score (ASPECTS) ≥ 6 on non-contrast CT (NCCT) and moderate to good collateral state on CT angiography (CTA) were divided into EVT group and standard medical treatment (SMT) group. The primary outcome was the rate of functional independence (90-day mRS ≤ 2). Safety outcomes were the occurrence of symptomatic intracranial hemorrhage (sICH) and the 90-day mortality.Results: Among the 288 enrolled patients (53.5% male, median age 64 years), there were 167 patients in the EVT group and 121 in the SMT group. After multivariable adjustments for potential confounders, EVT was associated with functional independence (adjusted OR: 3.052; 95% confidence interval (CI): 1.553– 5.997; p = 0.001). In the PSM cohort, 44.2% (42/95) of patients in the EVT group versus 18.9% (18/95) in the SMT group achieved functional independence (OR: 3.39, 95% CI: 1.763– 6.517), and there was a significant difference favoring EVT over the SMT in the overall distribution of mRS (OR: 2.170, 95% CI: 1.302– 3.618) at 90 days. The rate of sICH did not differ between the EVT and SMT groups (10.5% vs 8.4%, p = 0.804) nor did 90-day mortality (18.9% vs 22.1%, p = 0.719). No interaction was found in p-values with statistical significance in subgroup analysis.Conclusion: This real-world experience suggests that EVT for late-presenting stroke patients, based on small core on NCCT and moderate to good collaterals on CTA, is associated with better outcomes than SMT alone, with no increase in sICH and 90-day mortality rates.Keywords: endovascular treatment, late time window, propensity score matching, real-world study

This study aimed to evaluate the safety and efficacy of mechanical thrombectomy (MT) in patients with acute basilar artery occlusion (BAO) based on the baseline Basilar Artery on Computed Tomography Angiography (BATMAN) score.We selected patients from the BASILAR study and analyzed the effects and safety of standard medical therapy (SMT) and MT for patients with documented BATMAN scores. The patients were subgrouped according to their BATMAN score (0-3, 4-6, and 7-10). The primary outcome was a favorable functional outcome (modified Rankin Scale [mRS] ≤ 3) and mortality after 90 days.This study included 828 patients: 337 with poor BATMAN scores (0-3), 386 with moderate BATMAN scores (4-6), and 105 with good BATMAN scores (7-10). MT was associated with favorable functional outcomes in the poor (adjusted odds ratio [aOR], 11.96; 95% confidence interval [CI], 2.58-55.43; P = 0.002), moderate (aOR, 4.66; 95% CI, 2.11-10.28; P .001), and good (aOR, 7.71; 95% CI, 2.20-27.02; P = 0.001) BATMAN score subgroups. MT was also associated with low mortality rates in the poor (aOR, 0.10; 95% CI, 0.04-0.27; P 0.001) and moderate (aOR, 0.31; 95% CI, 0.16-0.57; P = 0.002) BATMAN score subgroups. The BATMAN score was significantly associated with favorable outcomes in both the SMT (aOR, 1.44; 95% CI, 1.08-1.93; P = 0.014) and MT (aOR, 1.31; 95% CI, 1.20-1.44; P 0.001) groups.Higher BATMAN scores were associated with improved prognosis and lower mortality rates after 3 months. MT was associated with improved outcomes in patients with low BATMAN scores despite their worse overall outcomes.ChiCTR1800014759, 2018/02/03.

We aimed to evaluate whether Alberta Stroke Program Early CT Score (ASPECTS) applied to hyperdense lesion on noncontrast CT obtained immediately post-thrombectomy (post-ASPECTS) is useful for predicting poor outcome. We retrospectively reviewed patients who underwent noncontrast CT (NCCT) immediately after mechanical thrombectomy between January 2017 and July 2020 in our comprehensive stroke center. We collected baseline NCCT and post-ASPECTS score. The sensitivity, specificity, and positive and negative predictive values of the post-ASPECTS in predicting clinical outcome were calculated. A total of 223 patients were included. The hyperdense lesion on NCCT immediately after endovascular thrombectomy presented in 85.7% (191/223) patients, poor clinical outcome was in 56.1% (112/191) of hyperdense lesion patients. Low post-ASPECTS was associated with poor outcome (OR 0.390; 95% CI 0.258-0.589; P = .001), with an AUCROC curve of 0.753 (95% CI 0.684-0.822), while baseline NCCT-ASPECTS was not (OR 0. 754; 95% CI 0. 497-1.144; P = .185). A score ≤ 7 in post-ASPECTS was the best cut-off to poor clinical outcome (sensitivity 84.8%; specificity 52.7%; positive predictive value 68.4%; negative predictive value 73.8%). Our results point to the proportion of patients who present hyperdense lesion on NCCT is very high, post-ASPECTS could predict poor clinical outcomes in patients with stroke treated with endovascular mechanical thrombectomy, and post-ASPECTS may achieved better predictive value than baseline ASPECTS.

Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022.Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy.The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours.Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]).Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke.Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.

Background: Despite reports on neuroprotective effects of dietary theobromine intake, whether dietary theobromine can exert beneficial effects on cognitive function is unclear. We aimed to investigate the association between dietary theobromine and cognitive function in old American population.Methods: We collected data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey, a cross-sectional survey. Daily dietary theobromine was treated as a continuous variable and a log transform. Cognitive function was measured by four tests: Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning tests, CERAD delayed recall test, animal fluency test, and digit symbol substitution test (DSST). We conducted linear regression analyses and subgroup analyses to study the association between theobromine intake and cognitive performance. Basic characteristics, lifestyle factors, disease history, and nutritional intake were adjusted in these models.Results: A total of 2,845 participants were included in this study. Daily theobromine intake was not significantly different between the 2011-2012 and 2013-2014 cycles. The CERAD-immediate and delayed recall scores were significantly different between these two cycles, but not the animal fluency score or digital symbol score. The daily dietary theobromine intake in log form was positively associated with immediate recall score (β, 95% CI, P: 0.661, 0.222-1.101, P: 0.232, 0.016-0.449, 0.04), and DSST score (β, 95% CI, P: 1.395, 0.140-2.649, 0.03) in the fully adjusted model, but not with the animal fluency score (β, 95% CI: 0.001, -0.122-0.907, 0.13). Sensitive analyses showed that L-theobromine intake was linearly associated with cognitive performance.Conclusions: Daily theobromine intake was associated with cognitive performance in a large national representative population. However, further research is needed in order to corroborate our findings.

IMPORTANCE: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. OBJECTIVE: To evaluate the association between EVT and clinical outcomes of patients with acute BAO. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. MAIN OUTCOMES AND MEASURES: The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality. RESULTS: A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55]; P

Objective The objective of this study was to investigate and discuss the therapeutic effect of pre-operative tirofiban on patients with acute ischemic stroke (AIS) with mechanical thrombectomy (MT) within 6–24 h. Patients and methods We retrospectively queried our AIS database from January to November 2018, and selected 99 patients with AIS within 6–24 h and evidence of proximal large vessel occlusion who were suitable for MT. They were divided into two groups, group A (with tirofiban, n = 56) and group B (without tirofiban, n = 43), according to whether they were intravenously infused with tirofiban before MT. The baseline characteristics and outcomes of patients were subjected to statistical analysis, including age, gender and risk factors, occlusion site, the time from onset to door, time of door to puncture, baseline National Institutes of Health Stroke Scale (NIHSS), pre-operative Alberta stroke programme early CT (ASPECT) score, angioplasty/stenting, modified Rankin Scale score 0–2 at 3 months, symptomatic haemorrhage and mortality, the time of door to recanalization, endovascular procedure time, 7-day (7d) NIHSS score, and a modified treatment in cerebral infarction (m-TICI) grade of 2b or 3. All of the thrombi were analysed by histopathology. Results The differences in the time of door to recanalization, endovascular procedure time, 7d NIHSS score and the m-TICI were significantly different between groups ( P 0.05 each). Histopathological analysis showed that all thrombi contained different amounts of platelets, fibrinogen, Haemamoebas and red blood cells. Conclusion The use of tirofiban before MT can shorten the procedure time and improve the recanalization rate of occluded vessels in AIS patients.

Background: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. This study aimed to evaluate the safety and efficacy of EVT for patients with acute BAO. Methods: The EVT for acute basilar artery occlusion study (BASILAR) was a nationwide prospective registry of consecutive patients presenting with an acute symptomatic and radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China. Patients with acute BAO within 24 hours of estimated occlusion time were divided into standard medical treatment (SMT) plus EVT or SMT alone groups. The primary outcome was the improvement in the modified Rankin Scale (mRS, scores range from 0 to 6, with higher scores indicating greater disability) score at 90 days across the two groups assessed as a common odds ratio (cOR) using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as mRS ≤ 3 (indicating ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. Findings: Between January, 2014, and May, 2019, 829 patients were recruited into the study, 647 treated with SMT plus EVT and 182 with SMT alone. 90-day functional outcomes were substantially improved by EVT (adjusted cOR, 3·07 [95% confidence interval, 2·07 to 4·54], P < 0·001). Moreover, EVT was associated with a significantly higher rate of 90-day mRS ≤ 3 (adjusted OR, 4·70 [95% CI, 2·53 to 8·75], P < 0·001) and a lower rate of 90-day mortality (adjusted OR, 2·93 [95% CI, 1·95 to 4·40], P < 0·001) despite an increase in sICH (7·1% vs. 0·5%, P < 0·001). Interpretation: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality. Trial Registration: BASILAR is registered on www.chictr.org.cn (ChiCTR180001475). Funding Statement: This work was supported by National Science Fund for Distinguished Young Scholars (No. 81525008), Chongqing Major Disease Prevention and Control Technology Research Project (No. 2019ZX001)， Army Medical University Clinical Medical Research Talent Training Program (No. 2018XLC2013 and No. 2018XLC3039), and Major clinical innovation technology project of the Second Affiliated Hospital of the Army Medical University (No. 2018JSLC0017). Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Xinqiao hospital, Army Medical University, Chongqing, China and each subcenter. All patients or their legally authorized representatives provided signed, informed consent.

Supplemental Digital Content is available in the text, Background: Available evidence shows conflicting results with regard to a potential detrimental effect of hypertension on clinical outcomes in patients who undergo mechanical thrombectomy (MT). We performed a meta-analysis to evaluate the impact of hypertension on the prognosis of patients with acute ischaemic stroke (AIS) treated by MT. Methods: We systematically reviewed previous studies in the PubMed, EMBASE, and Cochrane library databases that reported MT outcomes in AIS patients and their relationships with hypertension or blood pressure. We used a poor outcome (modified Rankin score >2 at 3 months) as the primary end point. Mortality and symptomatic intracranial hemorrhage were the secondary end points. We incorporated a random effect for trials in all models. Results: Data from 6650 patients in 31 articles that evaluated the effect of hypertension or blood pressure on outcomes after MT were included. Compared with patients without hypertension, patients with hypertension had significantly higher odds of a poor outcome (odds ratio 0.70; 95% confidence interval 0.57–0.85; I2 = 43%) and higher mortality (odds ratio 1.70; 95% confidence interval 1.26–2.29; I2 = 33%). Symptomatic intracranial hemorrhage did not differ by patient hypertension status. Conclusions: The present study confirms that hypertension and high blood pressure are associated with a poor outcome at 3 months after MT in AIS patients. However, the causal relationship between hypertension and a poor outcome remains undetermined, and further investigations are required to ascertain whether AIS patients receiving MT could benefit from intensive blood pressure control.

The objective of this study was to compare clinical outcomes in patients who with unfavorable vascular anatomy underwent mechanical thrombectomy (MT) by common carotid artery access versus transfemoral approach. A retrospective review was performed in our hospital database to identify patients with challenging vascular anatomy who underwent MT for anterior circulation large vessel occlusion (LVO) between August 2015 and November 2018. Transcarotid and transfemoral cohorts were compared. Patient characteristics, procedural techniques, clinical outcomes were recorded. A total of 52 patients were included, 16 (31%) underwent MT via transcarotid access. There were no significant differences in patient characteristics, intravenously recombinant tissue plasminogen activator therapy, clot location, or carotid tortuosity and presence of aortic arch type. There were significant differences in clinical outcomes between the 2 cohorts, including mean access-to-reperfusion time (84 vs 44 minutes; P = .000), poor clinical outcome (modified Rankin scale >2) at 90 days follow-up (37.5% vs 63.9%; P = .034). But there were no significant differences in successful revascularization rates (thrombolysis in cerebral infarction score ≥2b 87.5% vs 80.6%; P = .541), post-thrombectomy symptomatic intracranial hemorrhage (12.5% vs 13.9%; P = .892), and mortality (12.5% vs 22.2%; P = .412) were similar between transcarotid and transfemoral cohorts. Our results demonstrate that transcarotid access for MT of anterior circulation LVO in patients with unfavorable vascular anatomy may be considerable. Transcarotid access may be better than transfemoral access in well-selected unfavorable vascular anatomy patients undergoing MT.