Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Intravenous Tirofiban Versus Alteplase Before Endovascular Treatment in Acute Ischemic Stroke: A Pooled Analysis of the DEVT and RESCUE BT Trials.

BACKGROUND: The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion. METHODS: This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed. RESULTS: One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P=0.51) and mortality (17.8% versus 19.4%; P=0.76). The propensity score overlap weighting analyses showed consistent outcomes. CONCLUSIONS: Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Efficacy and safety of tirofiban combined with endovascular therapy for basilar artery occlusion stroke due to large artery atherosclerosis.

BACKGROUND: This study aimed to evaluate the efficacy and safety of adjuvant tirofiban in patients with acute basilar artery occlusion due to large-artery atherosclerotic (LAA) receiving endovascular therapy (EVT). METHODS: This was a non-randomized, multicenter study using data from the Endovascular Treatment for Acute BASILAR Artery Occlusion (BASILAR) registry. Patients with acute basilar artery occlusion due to LAA within 24h of symptom onset who underwent EVT were included. Patients were divided into tirofiban and non-tirofiban groups according to whether tirofiban was used. The primary outcome was the ordinal modified Rankin scale score at 90 days. Safety outcomes were mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h. RESULTS: A total of 417 patients were included, of whom 275 patients were in the tirofiban group and 142 patients in the non-tirofiban group. Compared with patients in the non-tirofiban group, patients in the tirofiban group were associated with a favorable shift in functional outcome at 90 days (6[4-6] vs 5 [2-6]; adjusted common OR, 2.51; 95 % CI, 1.64-3.83). The mortality was lower in the tirofiban group than the non-tirofiban group (40.7 % vs 58.5 %; adjusted OR, 0.35; 95 % CI, 0.21-0.56). The rate of sICH was 12.2 % in the non-tirofiban group and 5.2 % in the tirofiban group (adjusted OR, 0.37; 95 % CI, 0.17-0.80; P = 0.012). CONCLUSION: Tirofiban plus EVT might improve functional outcomes with a good safety for patients with acute basilar artery occlusion due to LAA. The results need to be confirmed in a randomized trial.

Tim-3, PD-1, CD244 and Foxp3 Positive T Cells' Relation to the Prognosis of Dermatomyositis and Polymyositis Patients.

OBJECTIVE: To explore the frequency of circulating CD4+ T cells expressing PD-1+, TIM-3+ in polymyositis (PM) and dermatomyositis (DM) patients and its correlation with inflammatory factors, CD244+ and FOXP3+ T cell subtypes and prognosis. STUDY DESIGN: Observational study. Place and Duration of the Study: Ganzhou people's Hospital, Ganzhou, Jiangxi, China, from July 2019 to June 2021. METHODOLOGY: PM and DM patients were treated according to the institution's guidelines and followed up for 2 years. Fifty healthy volunteers were enrolled as controls. Serum interleukin (IL)-6, C-reactive protein (CRP), IL-17, and tumour necrosis factor α (TNF-α) levels were detected by enzyme-linked immunosorbent assay (ELISA). TIM-3+, PD-1+, CD244+, and FOXP3+ expressions were measured using flow cytometry. Inability to live normally, recurrence or death was defined as poor prognosis. RESULTS: The ESR, ALT, AST, LDH and ferritin concentration in PM/DM patients were remarkably elevated than that in healthy volunteers. The frequencies of PD-1+, TIM-3+, CD244+, and FOXP3+ were all remarkably enhanced in PM/DM patients compared with the healthy volunteers. The frequencies of PD-1+, TIM-3+, FOXP3+, and TIM-3+/PD-1+ T cells were significantly elevated in the poor prognosis group compared with the good prognosis group. The frequency of CD4+TIM-3+PD-1+ had satisfactory diagnostic value for PM/DM patients with bad prognoses. IL-17, TIM-3+, PD-1+and TIM-3+ PD-1+ were the risk factors for PM/DM patients with bad outcomes. CONCLUSION: The frequency of circulating CD4+ T cells expressing TIM-3+PD-1+ could be used to predict the prognosis of PM/DM patients. KEY WORDS: Tim-3, PD-1, Dermatomyositis, Polymyositis, Inflammatory.

Hydrogel of HEMA, NVP, and Morpholine-Derivative Copolymer for Sulfate Ion Adsorption: Behaviors and Mechanisms.

SO42--containing compounds are widely present in wastewater generated from various industries and mining industries, such as slag leachate, pulp and paper wastewater, modified starch wastewater, etc. When the concentration of SO42- is too high, it will not only be corrosive to metal equipment but also accumulate in the environmental media. Based on this, a novel cationic hydrogel HNM was synthesized in this study by introducing morpholine groups into the conventional hydrogel HEMA-NVP system for the adsorption of SO42- in aqueous solutions. Characterizations by Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that morpholine groups had been introduced into the as-synthesizedhydrogels. The scanning electron microscope (SEM) characterization results show that the introduction of morpholine groups changed the surface of the hydrogel from micron-scale wrinkles to nanoscale gaps, increasing the contact area with the solution. The results of static water contact angle (WCA), equilibrium water content (EWC), and SO42- adsorption capacity show that the introduction of morpholine groups not only further improved the equilibrium water content and hydrophilicity of the hydrogel but also greatly improved the SO42- adsorption capacity of the hydrogel, with the maximum SO42- adsorption amount of 21.59 mg/g, which was much higher than that of the hydrogel without morpholine groups of 5.15 mg/g. Further studies found that the adsorption of SO42- on the hydrogel HNM was pH-dependent, and acidic conditions were favorable for the adsorption. Therefore, the introduction of morpholine groups greatly enhanced the ability of conventional HEMA-NVP hydrogels to remove SO42- from aqueous solutions.

Futile Recanalization After Endovascular Treatment in Patients With Acute Basilar Artery Occlusion.

BACKGROUND: It is estimated that >50% of acute basilar artery occlusion (ABAO) patients with successful reperfusion after endovascular treatment (EVT) have futile recanalization. However, few studies investigated the reasons behind this. OBJECTIVE: To identify the factors associated with futile recanalization in ABAO after successful reperfusion. METHODS: We recruited patients with successful reperfusion (expanded Thrombolysis In Cerebral Infarction score of ≥2b) after EVT from the Basilar Artery Occlusion Study registry. Patients were divided into meaningful recanalization (90-day modified Rankin Scale 0-3) and futile recanalization (90-day modified Rankin Scale 4-6) groups. Multivariable logistic regression analyses were used to identify the predictors of futile recanalization. RESULTS: A total of 522 patients with successful reperfusion were selected. Of these, 328 patients had futile recanalization and 194 had meaningful recanalization. Multivariable logistic regression shows that higher neutrophil-to-lymphocyte ratio ( P = .01), higher baseline National Institutes of Health Stroke Scale score ( P < .001), longer puncture to recanalization time ( P = .02), lower baseline posterior circulation Alberta Stroke Program Early CT score ( P < .001), lower posterior circulation collateral score ( P = .02), incomplete reperfusion ( P < .001), and diabetes mellitus ( P < .001) were predictors of futile recanalization. CONCLUSION: Higher neutrophil-to-lymphocyte ratio, longer puncture to recanalization time, incomplete reperfusion, stroke severity, lower baseline posterior circulation Alberta Stroke Program Early CT score, poor collaterals, and diabetes mellitus were independent predictors of futile recanalization in patients with ABAO with successful reperfusion after EVT. Moreover, multiple stent retriever passes were associated with a high proportion of futile recanalization in patients with late time windows.

Effect of endovascular treatment within 6 hours for acute basilar artery occlusion.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of endovascular treatment (EVT) plus standard medical treatment (SMT) in patients with acute basilar artery occlusion (BAO) within 6 hours of the estimated occlusion time, based on a Chinese population. METHODS: The authors selected patients from the Endovascular Treatment of Acute Basilar Artery Occlusion Study (BASILAR) registry, which was a nationwide prospective registry, within 6 hours after the estimated time of onset of a stroke in acute BAO. Patients were divided into the SMT-alone group or the EVT+SMT group according to treatment modalities. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale score between 0 and 3 at 90 days. Safety outcomes included death at 90 days and symptomatic intracerebral hemorrhage. RESULTS: The authors assessed 590 patients for eligibility. Of these patients, 127 received SMT alone and 463 were treated with EVT plus SMT. EVT was associated with a higher rate of a favorable functional outcome (adjusted OR 3.804, 95% CI 1.890-7.658; p < 0.001) and a lower proportion of deaths at 90 days (adjusted OR 0.364, 95% CI 0.223-0.594; p < 0.001). Lower age (adjusted OR 0.978, 95% CI 0.960-0.997; p = 0.022); lower baseline National Institutes of Health Stroke Scale score (adjusted OR 0.926, 95% CI 0.902-0.950; p < 0.001); higher baseline posterior circulation Alberta Stroke Program Early CT Score (adjusted OR 1.681, 95% CI 1.424-1.984; p < 0.001); absence of diabetes mellitus (adjusted OR 0.482, 95% CI 0.267-0.871; p = 0.016); and modified Thrombolysis in Cerebral Infarction scores 2b-3 (adjusted OR 5.117, 95% CI 2.304-11.367; p < 0.001) were independent factors for a favorable outcome in the EVT+SMT group. CONCLUSIONS: Based on the study design, patients with acute BAO who received EVT within 6 hours were associated with improved favorable outcome and decreased deaths compared with patients who received SMT. Predictors of desirable outcome in patients undergoing EVT included lower age, lower baseline National Institutes of Health Stroke Scale score, higher baseline posterior circulation Alberta Stroke Program Early CT Score, absence of diabetes mellitus, and modified Thrombolysis in Cerebral Infarction scores 2b-3.

Effect of the anastomosis between the posterior inferior cerebellar artery and the superior cerebellar artery on outcomes of acute basilar artery occlusion after endovascular treatment.

BACKGROUND: The effects of secondary collateral compensation on outcomes remain unclear in patients with acute basilar artery occlusion (BAO) after endovascular treatment (EVT). This study aimed to evaluate the benefits of the anastomosis between the posterior inferior cerebellar artery (PICA) and the superior cerebellar artery (SCA) in BAO after EVT. METHODS: This cohort study was conducted using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry. Patients with acute BAO and treated with EVT were included. The primary outcome was a modified Rankin Scale score of 0-2 at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (SICH) and 90-day mortality. RESULTS: Of the 646 patients included in the study, 196 (30.3%) patients had a PICA-SCA anastomosis. The PICA-SCA anastomosis was significantly associated with independent functional outcome at 90 days (67/196 (34.2%) vs 109/450 (24.2%), adjusted OR (aOR) 1.80 (95% CI 1.13 to 2.86), p=0.01) and was significantly associated with a decreased rate of SICH (40/442 (9.0%) vs 5/193 (2.6%), aOR 0.29 (95% CI 0.11 to 0.76), p=0.01). No significant difference was found between PICA-SCA anastomosis and 90-day mortality (219/450 (48.7%) vs 80/196 (40.8%), aOR 0.72 (95% CI 0.48 to 1.08), p=0.11). Subgroup analysis showed that the association between independent functional outcome and PICA-SCA anastomosis was strongest in patients with middle BAO (27/77 (35.1%) vs 22/118 (18.6%), aOR 2.64 (95% CI 1.13 to 6.15), p=0.03). CONCLUSIONS: The PICA-SCA anastomosis is significantly associated with better functional outcomes in patients with acute BAO after EVT, especially in those with middle BAO.

Predictors of futile recanalization in basilar artery occlusion patients undergoing endovascular treatment: a post hoc analysis of the ATTENTION trial.

Background: Few studies have focused on factors associated with futile recanalization in patients with an acute basilar artery occlusion (BAO) that was treated with modern endovascular therapy (EVT). The aim of this study was to explore the factors associated with futile recanalization in patients with an acute BAO presented within 12 h. Methods: This is a post-hoc analysis of the ATTENTION trial (The Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion, ClinicalTrials.gov, number NCT04751708). Demographics, clinical characteristics, acute stroke workflow interval times, and imaging characteristics were compared between the futile recanalization and favorable recanalization groups. The favorable outcome was defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, successful reperfusion was defined as thrombolysis in cerebral infarction (TICI) 2b and 3 on the final angiogram, and futile recanalization was defined as failure to achieve a favorable outcome despite successful reperfusion. A multivariate analysis was performed to identify the predictors of futile recanalization. Results: In total, 185 patients were included in the final analysis: 89 (48.1%) patients had futile recanalization and 96 (51.9%) patients had favorable recanalization. In the multivariable logistic regression analysis, older age (OR 1.04, 95% CI 1.01 to 1.08, p = 0.01) and diabetes mellitus (OR 3.35, 95% CI 1.40 to 8.01, p = 0.007) were independent predictors of futile recanalization. Conclusion: Futile recanalization occurred in nearly half of patients with acute BAO following endovascular treatment. Old age and diabetes mellitus were identified as independent predictors of futile recanalization after endovascular therapy for acute BAO.

Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Endovascular treatment for acute basilar artery occlusion due to different stroke etiologies of large artery atherosclerosis and cardioembolism.

Introduction: Stroke etiology may affect the prognosis of acute basilar artery occlusion (BAO). This study aimed to estimate the efficacy and safety of endovascular treatment (EVT) in BAO strokes due to the underlying stroke etiologies of large artery atherosclerosis (LAA) and cardioembolism (CE). Patients and methods: Patients with LAA and CE subtypes from the registry EVT for Acute Basilar Artery Occlusion Study (BASILAR) were selected for this analysis. We estimated the EVT treatment effect relative to standard medical treatment (SMT) in these patients by using a propensity score approach with inverse probability of treatment weighted estimation. Outcomes included 90-day favorable functional outcomes (modified Rankin scale (mRS) 0-3), functional independence (mRS 0-2), all-cause mortality, and symptomatic intracranial hemorrhage (sICH). Results: A total of 744 patients were included in the final analysis. After weighting with inverse probability of treatment estimation, the patients who, based on their characteristics, were treated with EVT rather than SMT, demonstrated higher rates of favorable functional outcomes in both the LAA (29.2% vs 11.7%, adjusted OR with 95% CI: 4.34 [2.15-8.78], p < 0.001) and the CE subtype (36.0% vs 8.1%, adjusted OR with 95% CI: 9.14 [1.96-42.55], p = 0.005). A similar finding was also observed for functional independence. EVT patients also demonstrated lower rates of mortality than SMT. Among EVT patients, no significant difference was observed in mortality or sICH between LAA and CE groups, but LAA patients had lower rates of favorable functional outcome and functional independence (29.2% vs 37% and 24.2% vs 32.9%, respectively), where the latter remained significant after adjustment for imbalances in baseline data (p = 0.04). Conclusions: In acute BAO strokes, both LAA and CE patients who, based on their characteristics, were treated with EVT rather than SMT, demonstrated better outcomes. Among EVT patients, LAA and CE subtypes displayed important baseline and treatment differences, and LAA patients were less likely to achieve functional independence at 3 months, but mortality and sICH were similar between LAA or CE subtypes. These results need to be confirmed in future clinical trials.

Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.

Importance: 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. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: 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. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: 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. Results: 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%]). Conclusions and Relevance: 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. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

Five-Year Outcomes After Endovascular Treatment for Large Vessel Occlusion Stroke.

Background: The long-term outcomes of acute large vessel occlusion (LVO) in anterior circulation treated by endovascular treatment (EVT) remains to be determined. The aim of this study was to assess the 5-year outcomes of patients with LVO who underwent EVT. Methods: This study was an observational, nationwide registry of consecutive patients with acute LVO who received EVT in 28 comprehensive stroke centers in China. The primary outcome was the proportion of favorable outcome [modified Rankin Scale score (mRS) 0-2] at 5 years. Secondary outcomes included proportions of patients with excellent outcome (mRS 0-1), all-cause mortality and risk of stroke recurrence at 5 years. Results: A total of 807 patients were included into the study and had 90-day follow-up data, 657 patients had 5-year follow-up data. At 90 days, 218 patients (27.0%) had an excellent outcome, 349 patients (43.2%) had a favorable functional outcome. 199 patients (24.7%) died. At 5 years, 190 patients (28.9%) had an excellent outcome, 261 patients (39.7%) had a favorable functional outcome, 317 patients (48.2%) died and 129 (28.2%) had stroke recurrence. Because of missing 5-year follow-up data, among available 269 patients who achieved functional independence at 90 days, 208 (77.3%) maintained favorable outcome, 19 (7.1%) had disability (mRS 3-5) and 42 (15.6%) died at 5 years. Furthermore, among available 189 patients with mRS 3-5 at 90 days, 53 (28.0%) patients achieved favorable functional outcome, 60 (31.7%) patients maintained unfavorable functional outcome and 76 (40.2%) patients died within 5 years. Multivariate analyses identified that younger age [odds ratio (OR): 0.96; 95% CI, 0.93-0.99; P = 0.009], lower mRS at 90 days (OR: 0.15; 95% CI, 0.10-0.23; P < 0.001) and absence of stroke recurrence (OR: 0.001; 95% CI, 0.000-0.006; P < 0.001) were significantly associated with favorable outcome at 5 years. Advanced age (OR: 1.06, 95% CI, 1.04-1.08; P < 0.001), higher mRS at 90 days (OR: 0.84; 95% CI, 0.73-0.98; P = 0.021) and atrial fibrillation (OR: 1.63; 95% CI, 1.02-2.60; P = 0.04) were independent factors for stroke recurrence. Conclusion: Our results indicated that the beneficial effect of EVT in patients with acute LVO can be sustained during the course of at least 5 years. Reducing the risk of stroke recurrence by anticoagulation for atrial fibrillation may be a crucial strategy to improve long-term outcome.

Basilar artery on computed tomography angiography score and clinical outcomes in acute basilar artery occlusion.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. UNIQUE IDENTIFIER: ChiCTR1800014759, 2018/02/03.

Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis.

Objective: Current therapies towards ischemic stroke (IS) are still not satisfied, and alternative strategies targeting ferroptosis may be another choice. The purpose of this study is to screen potential ferroptosis-related genes involving in IS. Methods: A rat model of IS was established via middle cerebral artery occlusion. Differentially expressed genes (DEGs) were screened from the model rats through transcriptional sequencing. Among the isolated DEGs, the expression of several attractive DEGs relating with ischemic injury was confirmed by qRT-PCR. Then, ATF3 relating with both IS and ferroptosis was selected a candidate gene for functional assays. After knockdown of ATF3 in the model rats, the infarction, histopathology, apoptosis, and ferroptosis in brain tissues were evaluated. Results: IS model was successfully established in rats, exhibiting the emergence of infarction area, histopathological injury, and enhanced cell apoptosis. Total 699 up-regulated DEGs and 461 down-regulated DEGs were screened from the model rats. qRT-PCR verified the up-regulation of Hspa1b, Tfpi2, Ptx3, and Atf3, and the down-regulation of Smyd1 and Tacr2 in the Model group compared with those in the Sham group. It is noteworthy that knockdown of ATF3 decreased the infarction area, relieved histopathological injury, weakened apoptosis, and inhibited ferroptosis in the model rats. Conclusion: Several candidate genes in relation with IS were revealed. More importantly, knockdown of ATF3 may relieve IS through inhibiting ferroptosis.

Extended Thrombolysis In Cerebral Infarction (eTICI) grade 2c: a potential angiographic target for endovascular treatment in acute basilar artery occlusion?

BACKGROUND: Higher extended Thrombolysis In Cerebral Infarction (eTICI) grades are associated with better clinical outcomes after endovascular treatment (EVT) for proximal intracranial occlusion of the anterior circulation. However, the relationship between eTICI grade and outcomes after EVT in patients with acute basilar artery occlusion (BAO) remains unclear. We aimed to explore which eTICI category was the cut-off correlating with better clinical outcomes in patients with BAO undergoing EVT. METHODS: We included patients treated via EVT from the BASILAR study. Multivariable logistic regression analyses were performed to assess the impact of eTICI grades on 90-day favorable functional outcomes, defined as a modified Rankin Scale (mRS) score of 0-3. Other outcomes were functional independence (mRS 0-2), all-cause mortality, and symptomatic intracranial hemorrhage. RESULTS: Among 647 patients treated with EVT, 127 (19.6%), 128 (24.5%), 110 (21.1%), and 282 (54%) patients achieved eTICI grades of 0-2a, 2b, 2c, and 3, respectively. Compared with eTICI grades 0-2a, higher rates of favorable functional outcomes (adjusted OR (aOR) 2.96, 95% CI 1.33 to 6.57, and aOR 7.40, 95% CI 3.63 to 15.09, respectively) were observed for grades 2c and 3, not 2b (aOR 1.93, 95% CI 0.86 to 4.36). The risks of mortality and symptomatic intracranial hemorrhage were also lower for eTICI grades 2c and 3 than for grades 0-2a. CONCLUSIONS: An eTICI grade of 2c/3 may be a target for successful reperfusion after EVT in patients with acute BAO; however, further studies with larger sample sizes and clinical trials are needed.

Values of Baseline Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score for Treatment Decision of Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion. METHODS: The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0-4 versus 5-7 versus 8-10) and as a continuous variable. The primary outcomes included favorable functional outcomes (modified Rankin Scale ≤3) at 90 days and mortality within 90 days. RESULTS: In total, 823 cases were included: 468 with pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397), 317 with pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 38 with pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25). EVT was associated with higher rate of favorable outcomes (adjusted relative risk with 95% CI, 4.35 [1.30-14.48] and 3.20 [1.68-6.09]; respectively) and lower mortality (60.8% versus 77.6%, P=0.005 and 35.0% versus 66.2%, P<0.001; respectively) than SMT in the pc-ASPECTS 5 to 7 and 8 to 10 subgroups. Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥5. Furthermore, the prognostic effect of onset to puncture time on favorable outcome with EVT was not significant after adjustment for pc-ASPECTS (adjusted odds ratio, 0.98 [95% CI, 0.94-1.02]). CONCLUSIONS: Patients of basilar artery occlusion with pc-ASPECTS ≥5 could benefit from EVT. The baseline pc-ASPECTS appears more important for decision making and predicting prognosis than time to EVT. Registration: URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1800014759.

Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial.

Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. Design, Setting, and Participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. Main Outcomes and Measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%). Conclusions and Relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.

DEVT: A randomized, controlled, multicenter trial of direct endovascular treatment versus standard bridging therapy for acute stroke patients with large vessel occlusion in the anterior circulation - Protocol.

BACKGROUND: Eight randomized controlled trials have consistently shown that endovascular treatment plus best medical treatment improves outcome after acute anterior proximal intracranial large vessel occlusion strokes. Whether intravenous thrombolysis prior to endovascular treatment in patients with anterior circulation, large vessel occlusion is of any additional benefits remains unclear. OBJECTIVE: This study compares the safety and efficacy of direct endovascular treatment versus intravenous recombinant tissue-type plasminogen activator bridging with endovascular treatment (bridging therapy) in acute stroke patients with intracranial internal carotid artery or middle cerebral artery-M1 occlusion within 4.5 h of symptom onset. METHODS AND DESIGN: The DEVT study is a randomized, controlled, multicenter trial with blinded outcome assessment. This trial uses a five-look group-sequential non-inferiority design. Up to 194 patients in each interim analysis will be consecutively randomized to direct endovascular treatment or bridging therapy group in 1:1 ratio over three years from about 30 hospitals in China. OUTCOMES: The primary end-point is the proportion of independent neurological function defined as modified Rankin scale score of 0 to 2 at 90 days. The primary safety measure is symptomatic intracerebral hemorrhage at 48 h and mortality at 90 days. TRIAL REGISTRY NUMBER: ChiCTR-IOR-17013568 (www.chictr.org.cn).

Assessment of Endovascular Treatment for Acute Basilar Artery Occlusion via a Nationwide Prospective Registry.

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 < .001). Moreover, EVT was associated with a significantly higher rate of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P < .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P < .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P < .001). Conclusions and Relevance: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.