Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

TRIM29 (Tripartite Motif Containing 29) Alleviates NLRC4 (NLR Family CARD Domain Containing Protein 4) Inflammasome Related Cerebral Injury via Promoting Proteasomal Degradation of NLRC4 in Ischemic Stroke.

BACKGROUND: Neuroinflammation plays extremely crucial roles in the neurological damage mediated by ischemic stroke. TRIM29 (tripartite motif containing 29) has previously been proposed to contribute to the regulation of innate immunity, however, the effect of TRIM29 on ischemic stroke induced neurodegenerative processes and neuroinflammation still largely unexplored. In the current article, we aimed to investigate the function and the precise mechanisms of TRIM29 in ischemic stroke. METHODS: Middle cerebral artery occlusion mice model and oxygen-glucose deprivation cell model were established as in vivo and in vitro models of ischemic stroke. Quantitative real-time polymerase chain reaction (PCR), Western blot, and ELSIA were used to detect the expression levels of TRIM29, cytokines, and marker proteins. Immunofluorescence assay was performed to examine the extent of cell death. Different truncations were generated, and coimmunoprecipitation assays were used to confirm the protein interaction. Ubiquitination assay was performed to detect the ubiquitination levels. RESULTS: We found that the cerebral ischemia-reperfusion induced injury was aggravated in TRIM29 knockout mice after middle cerebral artery occlusion operation as well as the increased neurological deficits score. TRIM29 expression was also found to be up-regulated upon middle cerebral artery occlusion or OGD administration, and loss of TRIM29 promoted the apoptosis and pyroptosis of neurons and microglial cells induced by middle cerebral artery occlusion or OGD, consistent with the enhanced proinflammatory mediators production and activation of NLRC4 (NLR [NOD-like receptor] family CARD [caspase recruitment domain] domain containing protein 4) inflammasome. Furthermore, we observed that TRIM29 interacted with NLRC4 directly and promoted the K48-linked polyubiquitination of NLRC4, lead to the proteasomal degradation of NLRC4. CONCLUSIONS: In conclusion, for the first time, we revealed the role of TRIM29 in ischemic stroke and illustrated the direct relationship between TRIM29 and NLRC4.

Association of Stroke Subtype With Hemorrhagic Transformation Mediated by Thrombectomy Pass: Data From the ANGEL-ACT Registry.

BACKGROUND: The role of stroke etiology subtype in patients with acute large vessel occlusion on the occurrence of hemorrhagic transformation (HT) after endovascular treatment is poorly studied, and which factors mediate their relationship remains largely unknown. We utilized nationwide registry data to explore the association of stroke subtype (cardioembolism versus large artery atherosclerosis) with HT and to identify the possible mediators. METHODS: A total of 1015 subjects were selected from the ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke)-a prospective consecutive cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals in China between November 2017 and March 2019-and divided into large artery atherosclerosis (n=538) and cardioembolism (n=477) according to the Trial of ORG 10172 in Acute Stroke Treatment criteria. The types of HT included any intracerebral hemorrhage (ICH), parenchymal hematoma, and symptomatic ICH within 24 hours after endovascular treatment. The association between stroke subtype and HT was analyzed using a logistic regression model. Mediation analysis was done to assess how much of the effect of stroke subtype on HT was mediated through the identified mediators. RESULTS: Stroke subtype (cardioembolism versus large artery atherosclerosis) was associated with increased risk of any ICH (29.8% versus 16.5%; odds ratio, 2.03 [95% CI, 1.22-3.36]), parenchymal hematoma (14.3% versus 5.4%; odds ratio, 2.90 [95% CI, 1.38-6.13]), and symptomatic ICH (9.9% versus 4.7%; odds ratio, 2.59 [95% CI, 1.09-6.16]) after adjustment for potential confounders. The more thrombectomy passes in cardioembolism patients had a significant mediation effect on the association of stroke subtype with increased risk of HT (any ICH, 15.9%; parenchymal hematoma, 13.4%; symptomatic ICH, 14.2%, respectively). CONCLUSIONS: Stroke subtype is an independent risk factor for HT within 24 hours following endovascular treatment among acute large vessel occlusion patients. Mediation analyses propose that stroke subtype contributes to HT partly through thrombectomy pass, suggesting a possible pathomechanistic link. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03370939.

Combined Approach to Eptifibatide and Thrombectomy in Acute Ischemic Stroke Because of Large Vessel Occlusion: A Matched-Control Analysis.

BACKGROUND: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. METHODS: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0-2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5-6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. RESULTS: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P=0.043) and 3-month good outcomes (53.1% versus 33.3%; P=0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. CONCLUSIONS: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).

Novel Diffusion-Weighted Imaging Score Showed Good Prognostic Value for Acute Basilar Artery Occlusion Following Endovascular Treatment: The Pons-Midbrain and Thalamus Score.

BACKGROUND AND PURPOSE: Prognostic factors for outcome of endovascular treatment remains to be investigated in patients with acute basilar artery occlusion. We aimed to assess the prognostic value of a novel pretreatment diffusion-weighted imaging score: The Pons-Midbrain and Thalamus (PMT) score. METHODS: Eligible patients who underwent endovascular treatment due to acute basilar artery occlusion were reviewed. The PMT score was a diffusion-weighted imaging-based semiquantitative scale in which the infarctions of pons, midbrain, and thalamus were fully considered. The PMT score was assessed as well as the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score and Brain Stem Score. Good outcomes were defined as a modified Rankin Scale score of ≤3 at 90-day and successful reperfusion as Thrombolysis in Cerebral Infarction grades 2b/3. The associations between baseline clinical parameters and good outcomes were evaluated with logistic regression. RESULTS: A total of 107 patients with pretreatment magnetic resonance imaging were included in this cohort. The baseline PMT score (median [interquartile range], 3 [1-5] versus 7 [5-9]; P<0.001) and Brain Stem Score (median [interquartile range], 2 [1-4] versus 3 [2-5]; P=0.001) were significantly lower in good outcome group; the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score was higher in good outcome group without statistical significance. As a result of receiver operating characteristic curve analyses, the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score showed poor prognostic accuracy for good outcome (area under the curve, 0.60 [95% CI, 0.49-0.71]; P=0.081); The baseline PMT score showed significantly better prognostic accuracy for 90-day good outcome than the Brain Stem Score and National Institutes of Health Stroke Scale (area under the curve, 0.80 versus 0.68 versus 0.78, P=0.003). In addition, favorable PMT score <7 (odds ratio, 22.0 [95% CI, 6.0-80.8], P<0.001), Brain Stem Score <3 (odds ratio, 4.65 [95% CI, 2.05-10.55], P<0.001) and baseline National Institutes of Health Stroke Scale <23 (odds ratio, 8.0 [95% CI, 2.5-25.6], P<0.001) were associated with improved good outcome. CONCLUSIONS: In patients with acute basilar artery occlusion following endovascular treatment, the pretreatment diffusion-weighted imaging based PMT score showed good prognostic value for clinical outcome.

Thrombectomy Versus Combined Thrombolysis and Thrombectomy in Patients With Acute Stroke: A Matched-Control Study.

A recent randomized controlled trial DIRECT-MT (Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) compared the safety and efficacy of mechanical thrombectomy (MT) versus combined intravenous thrombolysis (IVT) and MT for acute large vessel occlusion. The current study utilized a prospective, nationwide registry to validate the results of the DIRECT-MT trial in a real-world practice setting. Subjects were selected from a prospective cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals from 26 provinces in China (ANGEL-ACT registry [Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke]) between November 2017 and March 2019. All patients eligible for IVT and receiving MT were reviewed and then grouped according to whether prior IVT or not (MT and combined IVT+MT). After a 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale, successful recanalization, door-to-puncture time, symptomatic intracranial hemorrhage, and intraprocedural embolization were compared. A total of 1026 patients, 600 in the MT group and 426 in the combined group, were included. Among 788 patients identified after matching, there were no significant differences in the 90-day modified Rankin Scale (median, 3 versus 3 points; P=0.82) and successful recanalization (86.6% versus 89.3%; P=0.23) between the two groups; however, patients of the MT group had a shorter door-to-puncture time (median, 112 versus 136 minutes; ß=−45.02 [95% CI, −68.31 to −21.74]), lower rates of symptomatic intracranial hemorrhage (5.5% versus 10.1%; odds ratio, 0.52 [95% CI, 0.30­0.91]), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.30­0.98]) than those of the combined group. This matched-control study largely confirmed the findings of the DIRECT-MT trial in a real-world practice setting, suggesting that MT may carry similar effectiveness to combined IVT+MT for acute large vessel occlusion patients, despite MT alone seems to be associated with a shorter in-hospital delay until procedure, lower risks of symptomatic intracranial hemorrhage, and embolization. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. METHODS: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. RESULTS: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56-73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55-72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P=0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213-2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065-2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325-3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085-3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098-2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222-13.385]). CONCLUSIONS: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Factors influencing early neurological improvement after mechanical thrombectomy among patients with acute basilar artery occlusion: a single center prospective observational cohort study.

The predictive value of and the influencing factors associated with early neurological improvement (ENI) among patients with acute basilar artery occlusion (BAO) have not been well studied. The present study aimed to evaluate whether ENI predicted a better functional outcome and to identify the influencing factors of ENI. We performed a prospective observational analysis among 187 patients with acute BAO who underwent endovascular treatment (EVT) in Beijing Tiantan Hospital from January 2012 to July 2018. ENI was defined as having a drop on the National Institutes of Health Stroke Scale (NIHSS) by 8 or more scores or having a NIHSS of 0-1 within 24 h after EVT. A multivariate logistic regression model with backward selection was used to identify the influencing factors associated with ENI. ENI had a sensitivity of 0.69 and a specificity of 0.68 to predict a favorable outcome at 90 days after EVT. In addition, patients with ENIs had lower modified Rankin Scale score (mRS) (median: 2.0 vs. 5.0, p < 0.001) and were more likely to survive (95.2% vs. 72.0%, p < 0.001) and achieve functional independence (74.2% vs. 36.8%, p < 0.001). NIHSS before EVT, complete recanalization, white blood cell counts and general anesthetics were significant factors associated with ENI. A one-unit higher NIHSS and complete recanalization were associated with 1.04 (95% CI 1.01-1.08) and 2.71 (95% CI 1.14-6.45) times higher odds of achieving ENI, respectively. In conclusion, in patients with acute BAO, ENI within 24 hours after EVT can predict favorable outcomes at 90 day. Patients with higher NIHSS, lower white blood cell counts before surgery, without general anesthetics and patients with complete recanalization were more likely to achieve ENIs.

Medium- and long-term effects of endovascular treatments for severely stenotic basilar arteries supported by multimodal imaging.

BACKGROUND: To evaluate the medium-and long-term effect of intravascular interventional therapy for symptomatic severe basilar artery stenosis supported by multimodal imaging. METHOD: After strict screening of 67 patients with symptomatic severe basilar artery stenosis (70-99%) with atherosclerotic stenosis, 67 patients with symptomatic recurrence after intensive drug treatment were treated with intravascular balloon dilatation and Enterprise stent implantation. Any stroke or death within 30 days after operation and any stroke and restenosis during medium-and long-term follow-up were recorded. RESULTS: ①The mean age of 67 patients (67lesions) was 57 ± 8 years old, and the technical success rate was 100%; ②Preoperative angiography showed that the collateral circulation was poor, and TICI was 1-2a while postoperative angiography showed that TICI was significantly improved to 2b-3; ③The average preoperative stenosis rate was 82 ± 9%, and the postoperative stenosis rate was reduced to 17 ± 10%; ④Before surgery, abnormal perfusion was found in the posterior circulation CTP; After the postoperative re-examination, the posterior circulation of CTP perfusion was significantly improved; ⑤Postoperative symptoms and neurological conditions improved significantly; ⑥Complications of perforating branch event occurred in 1 case after operation, and symptoms were relieved after more than 1 month of medication treatment, and mild neurological dysfunction remained. 1 case developed subacute thrombosis in the stent, which improved after active intra-arterial thrombolysis, and there was no residual neurological dysfunction; and 1 case of micro-guide wire being trapped by the distal vasospasm. ⑦67 patients were followed up by telephone, WeChat or imaging for 36-66 months. CONCLUSIONS: In summary intravascular balloon dilation + Enterprise stent implantation is safe and effective for the treatment of symptomatic severe atherosclerotic stenosis of the basilar artery, with high technical success rate, low perioperative complications, and good mid-term and long-term effects.

Characteristic and prognosis of acute large vessel occlusion in anterior and posterior circulation after endovascular treatment: the ANGEL registry real world experience.

There were limited studies comparing the anterior (AC) and posterior (PC) circulation acute ischemic strokes (AIS). Our study aimed to evaluate distinct features of AC and PC strokes regarding clinical, vascular risk, pathogenesis and outcome factors after endovascular procedures. This multicenter prospective study registered 873 patients with acute large occlusion of anterior circulation stroke (ACS) and posterior circulation stroke (PCS). Patients who underwent endovascular procedures were included in this study. The differences in ACS and PCS regarding baseline characteristics, post-operative intracranial hemorrhage and outcomes were evaluated. A total of 741 patients were included in the data analysis. Intravenous thrombolysis (31.5%), atrial fibrillation (22.7%) and stent thrombectomy (82.4%) were more frequently observed in ACS patients. While higher NIHSS score, hypertension (67.6%) and balloon angioplasty (20.7%) were more prevalent in PCS patients. Symptomatic intracranial hemorrhage was more common in ACS (7.4% vs 2.8%). However, a 3-month follow-up outcomes were better in ACS with higher functional independence and low mortality rate than PCS (46.8% vs 30.3% and 16.4% vs 33.8%, respectively, P < 0.01). In this large prospective study, there were significant differences in the pathogenesis of stroke and treatment procedure between ACS and PCS which influence the clinical outcome. These findings could lead to a tailored clinical procedures and treatment strategies to improve the prognosis in both groups.

Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke.

Background and Purpose- Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke. Methods- We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke. Results- We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation-treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation-induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-ß-activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1. Conclusions- We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.

Association of Perforator Stroke After Basilar Artery Stenting With Negative Remodeling.

Background and Purpose- We try to evaluate whether plaque features and perforator stroke after intracranial stenting is associated with the arterial remodeling patterns in patients with severe basilar artery stenosis. Methods- We studied patients with symptomatic intracranial arterial stenosis who underwent high-resolution magnetic resonance imaging from September 2014 to January 2017. Among them, patients with basilar artery stenosis underwent angioplasty and stenting were recruited. Arterial remodeling patterns were divided into negative or nonnegative remodeling. Plaque features were investigated by high-resolution magnetic resonance imaging, which includes plaque distribution, intraplaque hemorrhage, calcification, as well as enhancement patterns. Incidence of perforator strokes after intracranial stenting was recorded. Plaque features and incidence of poststenting perforator stroke were compared between negative and nonnegative remodeling. Results- Two hundred ninety-eight consecutive patients were enrolled. Among them, 30 patients fulfilled the inclusion criteria. There were 11 patients (36.7%) with negative remodeling and 19 (63.3%) with nonnegative remodeling. Twenty-six patients (86.7%) had diffuse distribution, 5 patients (16.7%) had intraplaque hemorrhage, 2 patients (6.7%) had calcification, and 17 patients (65.4%) had enhancement. Three patients had perforator stroke after stenting. Plaque features were similar between negative and nonnegative remodeling groups. Patients with negative remodeling were more likely to have perforator stroke after stenting comparing with patients with nonnegative remodeling (27.3% versus 0%, P=0.041). Conclusions- Perforator stroke after basilar artery stenting may be related to negative remodeling on high-resolution magnetic resonance imaging. The finding needs to be confirmed in future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02705599.

The impact of intraarterial, intravenous, and combined tirofiban on endovascular treatment for acute intracranial atherosclerotic occlusion.

Background and purpose: Adjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD). Methods: Patients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0-1, 0-2, and 0-3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population. Results: A total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0-5) vs. 1(0-4) vs. 1(0-4) vs. 3(0-5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45-1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78-2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64-1.64, P = 0.912). The adjusted OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27-0.98, P = 0.042) and 0.50 (95% CI, 0.26-0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18-0.94, P = 0.036), and the OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11-0.74, P = 0.011) and 0.25 (95% CI, 0.09-0.67, P = 0.006). Conclusions: Intra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO. Clinical trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT03370939.

Unsuccessful Recanalization versus Medical Management of Patients with Large Ischemic Core : Analysis of the ANGEL-ASPECT Randomized Trial.

PURPOSE: The outcomes of patients with large ischemic core who fail to recanalize with endovascular therapy (EVT) compared to medical management (MM) are uncertain. The objective was to evaluate the clinical and safety outcomes of patients who underwent EVT in patients with large ischemic core and unsuccessful recanalization. METHODS: This was a post hoc analysis of the ANGEL-ASPECT randomized trial. Unsuccessful recanalization was defined as patients who underwent EVT with eTICI 0-2a. The primary endpoint was 90-day very poor outcome (mRS 5-6). Multivariable logistic regression was conducted controlling for ASPECTS, occlusion location, intravenous thrombolysis, and time to treatment. RESULTS: Of 455 patients 225 were treated with MM. Of 230 treated with EVT, 43 (19%) patients had unsuccessful recanalization. There was no difference in 90-day very poor outcomes (39.5% vs. 40%, aOR 0.93, 95% confidence interval, CI 0.47-1.85, p = 0.95), sICH (7.0% vs. 2.7%, aOR 2.81, 95% CI 0.6-13.29, p = 0.19), or mortality (30% vs. 20%, aOR 1.65, 95% CI 0.89-3.06, p = 0.11) between the unsuccessful EVT and MM groups, respectively. There were higher rates of ICH (55.8% vs. 17.3%, p < 0.001), infarct core volume growth (142.7 ml vs. 90.5 ml, ß = 47.77, 95% CI 20.97-74.57 ml, p < 0.001), and decompressive craniectomy (18.6% vs. 3.6%, p < 0.001) in the unsuccessful EVT versus MM groups. CONCLUSION: In a randomized trial of patients with large ischemic core undergoing EVT with unsuccessful recanalization, there was no difference in very poor outcomes, sICH or death versus medically managed patients. In the unsuccessful EVT group, there were higher rates of any ICH, volume of infarct core growth, and decompressive craniectomy.

Use of the MynxGrip vascular closure device in patients undergoing interventional diagnosis or treatment: The PANDA multicenter, open-label, randomized controlled trial.

BACKGROUND: MynxGrip is a non-suture, balloon catheter- and extravascular sealant-based vascular closure device designed to help hemostasis after an arterial puncture. This study evaluated the efficacy and safety of MynxGrip versus manual compression for femoral artery access closure in patients undergoing diagnostic or interventional procedures. METHODS: The PANDA multicenter, parallel-group, open-label, randomized controlled trial enrolled patients undergoing a diagnostic or interventional procedure through femoral artery access between April 2019 and September 2020 at six centers in China. The participants were randomized 2:1 to the MynxGrip group and the manual compression group. Time to hemostasis and incidence of severe complications were the primary efficacy and safety endpoints, respectively. RESULTS: A total of 304 consecutive participants were included. The baseline characteristics were similarly distributed in the MynxGrip (n = 203) versus manual compression (n = 101) groups. Compared with the manual compression group, the median time to hemostasis and time to ambulation were significantly shorter (3.0 (interquartile range: 2.0, 4.0) vs 18.0 (11.0, 22.0) min, and 479.0 (275.0, 932.0) vs 1410.3 (1121.0, 1476.0) min, respectively; both p = 0.0001) in the MynxGrip group, with similar procedural success rate, and without severe complications in either group. The incidence of device-related adverse events was 11.8% in the MynxGrip group, most possibly or definitely unrelated. CONCLUSIONS: Compared with manual compression, the MynxGrip vascular closure device significantly shortens the times to hemostasis and ambulation without severe complications after diagnostic or interventional procedures through the femoral artery access.

Necessity and timing of angioplasty in acute large-vessel occlusion strokes due to intracranial atherosclerotic disease: A cohort analysis with data from the angel-ACT registry.

Background: The effects of angioplasty on intracranial atherosclerotic disease (ICAD)-related acute large-vessel occlusion stroke (LVOS) are unknown. We analyzed the efficacy and safety of angioplasty or stenting for ICAD-related LVOS and the optimal treatment duration. Methods: Patients with ICAD-related LVOS from a prospective cohort of the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemia Stroke registry were classified as follows: the early intraprocedural angioplasty and/or stenting (EAS) group was defined as the strategy using angioplasty or stenting without mechanical thrombectomy (MT) or one attempt of MT; the non-angioplasty and/or stenting (NAS) group, MT procedure without any angioplasty; and the late intraprocedural angioplasty and/or stenting (LAS) group, using same angioplasty techniques following two or more passes of MT. The primary endpoint was the modified Rankin Scale (mRS) score at 90 days. Other efficacy outcomes included mRS scores 0-1, mRS 0-2, and successful recanalization. Death within 90 days, and symptomatic ICH were safety endpoints. We use propensity score method to diminish the effect of treatment-selection bias. The odds ratio of recanalization rate and mRS score among EAS, NAS, and LAS groups were examined by unadjusted and adjusted logistic regression analysis among unweighted samples and inverse probability of treatment weighting (IPTW) samples. Results: We divided 475 cases into three groups. Functional outcomes at 90 days were better in the EAS group than in the NAS and LAS groups. The proportion of mRS 0-1, mRS 0-2, and successful recanalization cases were the highest in the EAS group. However, after IPTW, mortality rate among the three groups were similar (EAS vs. NAS vs. LAS: 19.0 vs. 18.1 vs. 18.7%, p = 0.98) as well as symptomatic intracranial hemorrhage within 24 h however, mortality rate and symptomatic intracranial hemorrhage among the three groups were similar. Logistic regression analysis in unweighted samples and IPTW samples both showed that EAS group had better outcomes. IPTW-adjusted logistic regression analysis demonstrated that the EAS group had better outcomes (mRS 0-1) than the NAS group (adjusted odds ratio [aOR], 0.55; 95% confidence interval [CI]: 0.34-0.88, p = 0.01) and LAS (aOR, 0.39; 95% CI: 0.22-0.68, p = 0.001). Conclusions: Angioplasty and/or stenting should be performed at an early stage for ICAD-related acute LVOS. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Does MRI add value in selecting patients for thrombectomy beyond the 6 h window? A matched-control analysis.

Background: Controversy exists regarding the need of advanced imaging for patient selection in the extended window. Aims: To analyze the effect of initial imaging modalities on clinical outcomes of patients underwent MT in the extended window. Methods: This was a retrospective analysis of a prospective registry, the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke (ANGEL-ACT) registry which was conducted at 111 hospitals between November 2017 and March 2019 in China. Primary study cohort and Guideline like cohort were identified, in each cohort, two imaging modalities for patient selection in 6 to 24 h window were defined: (1) NCCT ± CTA, (2) MRI. Guideline-like cohort were further screened based on key features of the DAWN and DEFUSE 3 trials. The primary outcome was 90 day mRS. The safety outcomes were sICH, any ICH and 90-day mortality. Results: After adjusting for covariates, there were no significant differences in 90 day mRS or any safety outcomes between two imaging modalities groups in both cohorts. All outcome measures of mixed-effects logistic regression model were consistent with propensity score matching model. Conclusion: Our results indicate that patients presented with anterior large vessel occlusion in the extended time window can potentially benefit from MT even in the absence of MRI selection. This conclusion needs to be verified by the prospective randomized clinical trials.

Rescue angioplasty and/or stenting after mechanical thrombectomy: who can benefit?

BACKGROUND: Angioplasty and/or stenting is a rescue therapy for mechanical thrombectomy (MT) in acute intracranial large vessel occlusion. This study was undertaken to determine whether rescue angioplasty and/or stenting improves the outcome after MT and to investigate whether outcomes differ by subgroup of rescue indication. METHODS: We performed propensity score matching (PSM) with data from a prospective multicenter registry of patients with acute large vessel occlusion receiving endovascular treatment. Patients were divided into the MT alone group and the MT with rescue therapy group. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. PSM was also performed in the failed MT (modified Thrombolysis In Cerebral Infarction (mTICI) 0-2a) and the residual severe stenosis (mTICI 2b-3) subgroups, respectively. RESULTS: 326 patients of mean±SD age 62.7±12.0 years (90 women, 27.6%) were matched from 1274 patients. In the matched cohort, functional independence at 90 days was higher in the rescue therapy group than in the MT alone group (44.2% vs 29.5%; OR 1.90, 95% CI 1.18 to 3.06, P=0.008). In the failed MT subgroup with 66 matched pairs, more patients had functional independence in the rescue therapy group than in the MT alone group (39.0% vs 17.0%; OR 3.12, 95% CI 1.29 to 7.59, P=0.01). In the residual stenosis subgroup with 63 matched pairs, functional independence rates were similar in the rescue therapy and the MT alone groups (51.6% vs 55.7%; OR 0.85, 95% CI 0.42 to 1.72, P=0.65). CONCLUSION: Rescue angioplasty and/or stenting could improve the clinical outcome in patients with acute large vessel occlusion with failed MT, while no benefit was seen in those with residual severe stenosis but substantial reperfusion.

Predictors of parenchymal hemorrhage after endovascular treatment in acute ischemic stroke: data from ANGEL-ACT Registry.

BACKGROUND: Parenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT). OBJECTIVE: To investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). METHODS: Subjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score. RESULTS: Of the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12-36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001). CONCLUSIONS: In Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting. TRIAL REGISTRATION NUMBER: NCT03370939.

[Study on effect and mechanism of salidroside on cognitive ability of Abeta1-40 -induced Alzheimer's disease model rats].

OBJECTIVE: To study the effect and possible impact mechanism of salidroside on cognitive ability of Alzheimer's disease (AD) model rats induced by amyloid beta peptide (Abeta1-40). METHOD: Abeta1-40 was injected into bilateral hippocampus to create the AD model. Afterwards, different doses of salidroside (25, 50, 75 mg x kg(-1)) were orally administered for 21 days. Rats' learning and memory abilities were detected by Morris water maze testing system. The levels of the superoxide dismutase (SOD), malondialdehyde (MDA), and the expression of nuclear factor-kappaB (NF-kappaB), inducible nitric oxide synthase (iNOS) and receptor for advanced glycation end products (RAGE) protein in hippocampus were also detected by different methods. RESULT: The place navigation test showed longer escape latency, low frequency of platform quadrant crossing per unit time, damage in learning capacity, significant decrease in SOD acivity in hippocampus, notable increase in MDA content, NF-kappaB, iNOS and RAGE protein expressions in rats. Salidroside (50, 75 mg x kg(-1)) significantly alleviated the impairments of learning and memory ability. The activity of SOD increased in salidroside (50 droside group compared with that of the Alzheimer's disease group (P < 0.01). CONCLUSION: Salidroside may treat Alzheimer's disease by inhibiting the oxidative stress.