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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke: Vascular and Interventional Neurology Vol. 1, No. S1 ( 2021-11)
    In: Stroke: Vascular and Interventional Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 1, No. S1 ( 2021-11)
    Abstract: Introduction : The ANGEL‐ASPECT trial (NCT 04551664) is an ongoing, multicenter, randomized controlled trial (RCT) currently being conducted in China. The goal of ANGEL‐ASPECT’s is to include the maximum patients with a true large core for whom EVT is not recommended under current guidelines with level 1 evidence. By enrolling patients with ASPECTS 〈 6, expanding the window to 24h from stroke onset (beyond the windows in DAWN and DEFUSE3), and defining large core volume as 〉 70 cc, ANGEL‐ASPECT maximizes the inclusion of patients with true large cores. What’s more, intracranial atherosclerotic disease (ICAD) is common in the Asian population while most of the previous trials have been performed in the Western world where ICAD is less prevalent. Methods : We reviewed the merits of ANGEL‐ASPECT’s design and suggest that it be included in the discussion of patient selection criteria in large core trials. Results : The primary goal of our trial is to determine whether EVT will benefit or harm AIS patients with LVO and a “large core” infarct. The inclusion criteria for ANGEL‐ASPECT are: 1. If ASPECTS is 3–5 and presentation is within 24 hours of onset, patients are enrolled without obtaining CTP. 2. If ASPECTS is 〉 5 and presentation is beyond 6 hours of onset, only patients with relative cerebral blood flow (rCBF) of 〈 30% by CTP or apparent diffusion coefficient (ADC) of 〈 620 on MRI and estimated core volume of 70–100 cc are enrolled. 3. If ASPECTS is 〈 3, only patients with rCBF 〈 30% or ADC on MRI 〈 620 and estimated core volume of 70–100 cc are enrolled. Patients are enrolled under a pre‐specified protocol. Each randomized patient is qualified by two core lab members who are available at all hours to calculate ASPECTS and infarct core volume using specialized, RAPID software. Conclusions : We believe that defining core volume using CTP can compensate for the inconsistencies of ASPECTS if we exclude patients with onset within six hours and core volume of 50–70 cc since these patients have already been shown to benefit from EVT in multiple RCTs. We believe that this decision captures more patients with true large core volumes for the trial. The ANGEL‐ASPECT inclusion criteria also eliminate the second group of “good ASPECTS + unfavorable CTP” . The sample size of our trial is calculated based on studies excluding these populations. The power of the trial was maintained for the relatively consistent large core volume patient population.
    Type of Medium: Online Resource
    ISSN: 2694-5746
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 3144224-9
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 5 ( 2022-05), p. 1580-1588
    Abstract: 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).
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 2 ( 2023-02), p. 327-336
    Abstract: Sex disparities in acute large vessel occlusion (LVO) following endovascular treatment (EVT) have been recently reported. However, there is uncertainty about the effect of sex differences on functional outcomes after EVT, particularly in an Asian population. The present study aimed to compare the clinical and safety outcomes between men and women with anterior circulation LVO treated with EVT. Methods: We analyzed data from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke: a Prospective Multicenter Registry Study) Registry, which was conducted at 111 hospitals from 26 provinces in China between November 2017 and March 2019. Men and women with anterior circulation LVO treated with EVT were matched using propensity scores. After a 1:1 propensity score matching, we compared the clinical outcomes including 90-day ordinal modified Rankin Scale distribution (primary outcome), procedure duration, successful reperfusion, symptomatic intracranial hemorrhage, and mortality. Furthermore, we explored sex modification on the primary outcome in subgroup analysis. Results: Of 1321 patients, 483 (36.6%) were women and 838 (63.4%) were men. The mean age for women and men were 68 and 62 years old, respectively. Among 578 patients identified after matching, there were no sex differences (men versus women) in 90-day ordinal modified Rankin Scale distribution (median [interquartile range], 4 [1–5] versus 3 [1–5], P =0.464), successful reperfusion (86.5% versus 91.0%, P =0.089), symptomatic intracranial hemorrhage (6.5% versus 7.9%, P =0.512), and mortality within 90 days (17.7% versus 17.0%, P =0.826). However, men had a longer median procedure duration than women (86 [52–128] versus 72 [48–110] minutes, β=14.51, [95% CI, 4.19–24.84]; P =0.006). Subgroup analysis showed that in patients with National Institutes of Health Stroke Scale score 〈 15, women tended to have a better outcome than men, whereas there was no gender effect in those with National Institutes of Health Stroke Scale score ≥15 ( P for interaction=0.032). Conclusions: Overall, this matched-control study from the ANGEL-ACT study showed similar clinical outcomes between men and women with anterior circulation LVO treated with EVT. However, in the subgroup of patients presenting with lower stroke severity (ie, National Institutes of Health Stroke Scale score 〈 15), women tended to have a better outcome than men highlighting a potential sex disparity for further investigation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1589-1600
    Abstract: 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. Methods: 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. Results: 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; β=−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, 0.30–0.91] ), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.30–0.98]) than those of the combined group. Conclusions: 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. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 6 ( 2022-06), p. 1984-1992
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 4 ( 2021-04), p. 1203-1212
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 14, No. 9 ( 2022-09), p. 875-880
    Abstract: Early neurological deterioration (END) may occur in some patients with acute large vessel occlusion (LVO) undergoing endovascular treatment (EVT). Despite several clear causes of END, such as symptomatic intracranial hemorrhage, failure of recanalization, and intraprocedure complications, a particular END, termed unexplained END (END unexplained ), exists. We aimed to investigate the incidence, independent predictors, and clinical impact of END unexplained after EVT in patients with acute LVO. Methods Subjects were selected from the ANGEL-ACT registry. END unexplained was defined as ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after EVT, without the causes listed above. Logistic regression analyses were performed to determine the independent predictors of END unexplained , as well as the association between END unexplained and 90-day outcomes assessed by modified Rankin Scale (mRS) score. Results Among the 1557 enrolled patients, the incidence of END unexplained was 4.3% (67/1557). Admission NIHSS ≤8 (OR=6.88, 95% CI 3.86 to 12.26, p 〈 0.001), general anesthesia (OR=3.15, 95% CI 1.81 to 5.48, p 〈 0.001), admission neutrophil to lymphocyte ratio 〉 5 (OR=2.82, 95% CI 1.61 to 4.94, p 〈 0.001), and number of EVT attempts 〉 3 (OR=2.11, 95% CI 1.14 to 3.89, p=0.018) were associated independently with a high risk of END unexplained . Furthermore, patients with END unexplained were associated with a shift toward worse 90-day outcomes (mRS 5 vs 3, common OR=5.24, 95% CI 3.22 to 8.52, p 〈 0.001). Conclusions END unexplained associated with poor 90day outcomes occurred in 4.3% of patients with acute LVO undergoing EVT. Several independent predictors of END unexplained were identified in this study, which should be considered in daily practice to improve acute LVO management. Clinical trial Registration http://wwwclinicaltrialsgov NCT03370939 .
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2506028-4
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2021-3-12)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2021-3-12)
    Abstract: Evidence exists uncovering that SRY-box transcription factor 9 (SOX9) plays a role in ischemic brain injury (IBI). Thus, the current study was conducted to elucidate the specific role of SOX9 and the mechanism by which SOX9 influenced IBI. Methods The IBI-associated regulatory factors were searched by bioinformatics analysis. The rat model of IBI was generated using middle cerebral artery occlusion (MCAO) treatment. Neuronal cells were exposed to oxygen-glucose deprivation (OGD). The expressions of SOX9, forkhead box O3 (FOXO3), transcription of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), and IκB kinase α (IKKα) in OGD-treated neuronal cells were characterized using reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. The interaction among CITED2, IKKα, and FOXO3 was identified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assays. Gain- and loss-of-function experiments were performed to verify the relationship among SOX9, FOXO3, CITED2, and IKKα and to investigate their functional effects on apoptosis and the inflammatory response of OGD-treated neuronal cells as well as neurological deficit and infarct area of the rat brain. Results SOX9, FOXO3, CITED2, and IKKα were highly expressed in OGD-treated neuronal cells. Silencing of SOX9 inhibited OGD-induced neuronal apoptosis and inflammatory response and reduced the neurological deficit and infarct area of the brain in the rats, which were caused by MCAO but were reversed by overexpressing FOXO3, CITED2, or IKKα. Conclusion Taken together, our study suggested that upregulation of SOX9 promoted IBI though upregulation of the FOXO3/CITED2/IKKα axis, highlighting a basic therapeutic consideration for IBI treatment.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 9
    In: Translational Stroke Research, Springer Science and Business Media LLC, Vol. 12, No. 2 ( 2021-04), p. 230-238
    Type of Medium: Online Resource
    ISSN: 1868-4483 , 1868-601X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2541897-X
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  • 10
    In: Neuroradiology, Springer Science and Business Media LLC, Vol. 65, No. 1 ( 2023-01), p. 177-184
    Type of Medium: Online Resource
    ISSN: 0028-3940 , 1432-1920
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1462953-7
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