Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on non-contrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS)≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from prospectively maintained databases. The primary outcome was favorable functional outcome (modified Rankin Scale score [mRS], 0-3) at 90 days. Safety outcomes included 48-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only (adjusted risk ratio [RR], 1.86; 95% CI, 1.43 to 2.42, P<0.001; adjusted risk difference [RD], 13.77; 95% CI, 7.40 to 20.15, P<0.001). The proportion of sICH was significantly higher in patients undergoing EVT (13.3% vs. 2.4%; adjusted RR, 5.17; 95% CI, 2.17 to 12.32, P<0.001; adjusted RD, 10.10; 95% CI, 6.12 to 14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8% vs. 49.0%; adjusted RR, 0.91; 95% CI, 0.77 to 1.07, P=0.24; adjusted RD, -5.91; 95% CI, -12.91 to 1.09, P=0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were high in the EVT group.

Blood glucose to predict symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke with large infarct core: a prospective observational study.

Introduction: Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding predictors and clinical implications of sICH after EVT, underscoring the significance of identifying risk factors to enhance prevention strategies. Therefore, the main objective of this study was to evaluate the incidence of sICH and identify its predictors after EVT in patients with large infarct core-AIS in the pre-circulation stage. Methods: Using data from the EVT for the Pre-circulation Large Infarct Core-AIS Study, we enrolled patients who were treated with EVT from the Prospective Multicenter Cohort Study of Early Treatment in Acute Stroke (MAGIC) registry. Baseline demographics, medical history, vascular risk factors, blood pressure, stroke severity, radiographic features, and EVT details were collected. The patients were classified into three groups: without intracranial hemorrhage (ICH), with asymptomatic intracranial hemorrhage (aICH), and sICH, based upon the occurrence of sICH. The main outcomes were the occurrence of sICH according to the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to identify independent predictors of sICH after EVT. Results: The study recruited a total of 490 patients, of whom 13.3% (n = 65) developed sICH. Patients with sICH had less favorable outcomes than those without intracranial hemorrhage (ICH) and those with aICH (13.8% vs. 43.5% vs. 32.2%, respectively; p < 0.001). The overall mortality was 41.8% (n = 205) at 90 days post-EVT. The univariate analysis revealed significant differences among the three groups in terms of blood glucose levels at admission, probability of favorable outcomes, incidence of brain herniation, and 90-day mortality. The multifactorial logistic regression analysis revealed that the blood glucose level at admission [odds ratio (OR) 1.169, p < 0.001, confidence interval (CI) 1.076-1.269] was an independent predictor of sICH. A blood glucose level of 6.95 mmol/L at admission was the best predictor of sICH, with an area under the ROC curve (AUC) of 0.685 (95% CI: 0.616-0.754). Discussion: The study findings demonstrated that the probability of sICH after EVT was 13.3% in patients with pre-circulation large infarct core-AIS, and sICH increased the risk of an unfavorable prognosis. Higher blood glucose levels at admission were associated with sICH after EVT in patients with pre-circulation large infarct core AIS. These findings underscore the importance of early management strategies to mitigate this risk.

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke.

Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

The impact of stress hyperglycemia ratio on short-term and long-term outcomes for acute basilar artery occlusion underwent endovascular treatment.

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.

BACKGROUND: Smad ubiquitination regulatory factor 2 (Smurf2) has been observed to alleviate ischemia-reperfusion injury. This study sought to explore the molecular mechanism of Smurf2-mediated forkhead box O4 (FOXO4) ubiquitination in oxygen-glucose deprivation/ reperfusion (OGD/R)-induced pyroptosis of cortical neurons. METHODS: Human cortical neurons (HCN-2) were subjected to OGD/R to establish a cell model of cerebral stroke. Smurf2, FOXO4, and doublecortin domain containing 2 (DCDC2) expressions were determined by RT-qPCR and Western blot. LDH release, pyroptosis-related proteins NLRP3, GSDMD-N, and cleaved-caspase-3, as well as inflammatory factors IL-1ß and IL-18, were assessed by LDH assay kit, Western blot, and ELISA. The ubiquitination level of FOXO4 was determined by ubiquitination assay. The bindings of Smurf2 to FOXO4 and FOXO4 to DCDC2 were testified by Co-IP, ChIP, and dual-luciferase assays. Rescue experiments were designed to validate the role of FOXO4/DCDC2 in the pyroptosis of HCN-2 cells. RESULTS: Smurf2 was weakly expressed, while FOXO4 and DCDC2 were prominently expressed in OGD/R-treated HCN-2 cells. Smurf2 overexpression promoted LDH release, reduced NLRP3, GSDMD-N, and cleaved-caspase-3 proteins, and decreased IL-1ß and IL-18 concentrations. Sumrf2 improved the ubiquitination level of FOXO4 to downregulate its protein level. FOXO4 is bound to the DCDC2 promoter to facilitate its transcription. Overexpression of FOXO4 or DCDC2 reversed the inhibition of Smurf2 overexpression on pyroptosis of OGD/Rtreated HCN-2 cells. CONCLUSION: Smurf2 overexpression facilitated the ubiquitination of FOXO4 to reduce its protein level, thereby suppressing DCDC2 transcription and restricting OGD/R-induced pyroptosis of cortical neurons.

Thrombectomy alone versus intravenous thrombolysis before thrombectomy for acute basilar artery occlusion.

BACKGROUND: Endovascular treatment (EVT) is a well-established approach for acute ischemic stroke. Whether bridging intravenous thrombolysis (IVT) before EVT confers any benefits remains uncertain. The objective of the study was to compare the efficacy and safety of direct EVT with or without bridging IVT in patients with acute basilar artery occlusion (BAO). METHODS: This multicenter cohort study enrolled 647 patients with acute BAO who underwent either bridging IVT before EVT or direct EVT from the BASILAR registry. The primary outcome was an independent functional outcome measured by the modified Rankin Scale (mRS) score of 0-2. Secondary outcomes included excellent functional outcome (mRS 0-1), favorable functional outcome (mRS 0-3), and mortality rate at 90 days, as well as symptomatic intracranial hemorrhage (sICH), and successful reperfusion between the two treatment groups. RESULTS: Direct EVT and bridging IVT before EVT exhibited similar primary outcomes (27.3% vs 27.7%, respectively) and distributions of mRS scores at 90 days. Moreover, rates of sICH and 90-day mortality were not significantly different between the two groups (7.3% vs 6.0%, adjusted OR (aOR) 0.79, 95% CI 0.34 to 1.86, P=0.84 for sICH; 46.8% vs 43.7%, aOR 0.86, 95% CI 0.54 to 1.38, P=0.53 for mortality). CONCLUSIONS: Among patients with acute BAO, functional outcomes were similar between those treated with bridging IVT before EVT and those treated with direct EVT, and there was no difference between the two groups in terms of sICH and mortality rates.

Intravenous tirofiban following successful reperfusion in intracranial large artery atherosclerotic stroke: A secondary analysis of a randomized clinical trial.

OBJECTIVE: This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. METHODS: Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0-2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02-2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; p = 0.44) or 90-day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; p = 0.27). INTERPRETATION: Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

Predictors of Mechanical Thrombectomy for Anterior Circulation Emergent Large-Vessel Occlusion in the Older Adults.

Few studies have reported the clinical outcomes of older adult patients with acute anterior circulation large-vessel occlusion (LVO) who underwent mechanical thrombectomy (MT). Therefore, we investigated the safety, functional outcomes, and predictors of MT for anterior circulation LVO in older adults. We enrolled patients with acute anterior circulation LVO from May 2018 to October 2021 in this retrospective study. Patients were divided into older (≥80 years) and young (<80 years) groups. Multivariable logistic regression analyses determined the safety, functional outcomes, and predictors of MT for anterior circulation LVO. We divided 1182 patients with acute ischemic stroke into young (18-79 years; 1028 patients) and older (≥80 years; 154 patients) groups. Compared with the young group, the older group had more unfavorable functional outcomes and increased mortality (P = .003). In the older adult patients, lower initial NIHSS score and higher ASPECTS were correlated with good outcomes. On the contrary, higher initial NIHSS score and lower ASPECTS were related to increased mortality. No difference was detected in symptomatic intracranial hemorrhage within 48 h between two groups. Increasing age was associated with lower rates of favorable functional outcomes and higher mortality rates. The lower initial NIHSS score combined with the higher ASPECTS may predict functional outcomes post-thrombectomy in older adults.

Association Between Admission Hyperglycemia and Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion.

INTRODUCTION: Admission hyperglycemia and high admission blood glucose levels have been associated with poor outcomes in acute ischemic stroke. However, the relationship between admission hyperglycemia and outcomes after endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) still remain unclear. This study aimed to investigate the association between admission hyperglycemia and clinical outcomes in ABAO following EVT. METHODS: Patients from the BASILAR registry with admission blood glucose levels treated with EVT were included. We defined admission hyperglycemia as blood glucose levels ≥ 7.8 mmol/L. The primary outcome was favorable outcome [defined as a modified Rankin Scale score (mRS) of 0-3] at 90 days, Secondary outcomes included other functional outcomes (mRS 0-2, mRS 0-1) at 90 days, symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality at 90 days. RESULTS: Of 545 eligible patients included, the median age was 65 (IQR, 56-73) years, and median blood glucose level was 7.36 (IQR, 6.10-9.66) mmol/L. Multivariable logistic regression analysis showed that admission hyperglycemia was associated with decreased favorable outcome (mRS 0-3) (adjusted odds ratio = 0.52; 95% CI 0.35-0.79; P = 0.001), and increased mortality (adjusted odds ratio = 2.67; 95% CI 1.82-3.91; P < 0.001). Restricted cubic spline regression analysis showed that the blood glucose level had a non-linearity association with favorable outcome and mortality, and that there was no association between admission hyperglycemia and sICH. CONCLUSIONS: Our study suggest that admission hyperglycemia is associated with an increased risk of poor functional outcomes and mortality in patients with ABAO treated with EVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR180001475.

Association between stress hyperglycemia and outcomes in patients with acute ischemic stroke due to large vessel occlusion.

AIMS: This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and clinical outcomes at 90 days in acute ischemic stroke due to large vessel occlusion receiving endovascular treatment. METHODS: The RESCUE BT trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial, consisting of 948 stroke patients from 55 centers in China. A total of 542 patients with glucose and glycated hemoglobin (HbA1C) values at admission were included in this analysis. SHR, measured by glucose/HbA1C, was evaluated as both a tri-categorical variable (≤1.07 vs. 1.08-1.29 vs. ≥1.30) and a continuous variable. The primary outcome was a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at 90 days. The secondary outcome included excellent functional outcome (mRS score ≤1) and safety outcomes, such as 90-day mortality and intracranial hemorrhage. The study was registered with Chictr.org.cn (ChiCTR-INR-17014167). RESULTS: Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving favorable functional outcome of mRS score of 0-2 (adjusted odds ratio, 0.44; 95% confidence interval, 0.28-0.69; p < 0.001) and excellent clinical outcome of mRS score of 0-1 (adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.79; p = 0.004) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for preexisting diabetes and Alberta Stroke Program Early Computed Tomography Score (ASPECTS). CONCLUSION: Stress hyperglycemia ratio, as measured by the glucose/HbA1C, was associated with a decreased odds of achieving a favorable functional outcome in patients with acute large vessel occlusion stroke at 90 days.

The MRI enhancement ratio and plaque steepness may be more accurate for predicting recurrent ischemic cerebrovascular events in patients with intracranial atherosclerosis.

OBJECTIVES: To assess the complementary value of high-resolution multi-contrast MRI (hrMRI) in identifying symptomatic patients with intracranial atherosclerosis (ICAS) who are likely to experience recurrent ischemic cerebrovascular events. METHODS: In this retrospective cohort study, eighty patients with acute ischemic events attributed to ICAS who underwent hrMRI examination between January 2015 and January 2019 were included. Median follow-up for all patients was 30 months (range: 1 to 52 months) and recurrent ischemic cerebrovascular events were recorded. Cox regression analysis and time-dependent ROC were performed to quantify the association between the plaque characteristics and recurrent events. RESULTS: During the follow-up, 14 patients experienced recurrent ischemic cerebrovascular events. Young males and those with diabetes and poor medication persistence were more likely to experience recurrent events. ICAS in patients with recurrence had significantly higher enhancement ratio and steepness which is defined as the ratio between the plaque height and length than those without (p < 0.001 and p = 0.015, respectively). After adjustment of clinical factors, enhancement ratio (HR, 13.13 [95% CI, 3.58-48.20], p < 0.001) and plaque steepness (HR, 110.27 [95% CI, 4.75-2560.91], p = 0.003) were independent imaging biomarkers associated with recurrent events. Time-dependent ROC indicated that integrated high enhancement ratio and steepness into clinical risk factors improved discrimination power with the ROC increased from 0.79 to 0.94 (p = 0.008). CONCLUSIONS: The enhancement ratio and plaque steepness improved the accuracy over traditional clinical risk factors in predicting recurrent ischemic cerebrovascular events for patients with ICAS. KEY POINTS: • High-resolution magnetic resonance imaging helps clinicians to evaluate high-risk Intracranial plaque. • The higher enhancement ratio and plaque steepness (= height/length) were the primary biomarkers associated with future ischemic cerebrovascular events. • High-resolution magnetic resonance imaging combined with clinical characteristics showed a higher accuracy for the prediction of recurrent events in patients with intracranial atherosclerosis.

Identification of Symptomatic Carotid Artery Plaque: A Three-Item Scale Combined Angiography With Optical Coherence Tomography.

Introduction: Symptomatic carotid disease conveys a high risk of recurrent stroke. Plaque morphology and specific plaque characteristics are associated with the risk of stroke. This study aimed to evaluate the detailed plaque features by optical coherence tomography (OCT) and develop a simple scale combining clinical indicators, digital subtraction angiography (DSA), and OCT imaging markers to identify symptomatic carotid plaque. Methods: Carotid plaques from consecutive patients who underwent carotid OCT imaging between June 2017 and June 2021 were evaluated. Clinical characteristics, DSA, and OCT data were compared between the symptomatic and asymptomatic groups. Logistic regression was performed to identify the factors associated with symptomatic carotid plaque and to develop a scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the scale. Results: A total of 90 carotid plaques from 90 patients were included (symptomatic 35.6%, asymptomatic 64.4%). Three main factors were found to be associated with symptomatic carotid plaque: high-density lipoprotein cholesterol (HDL-C) <0.925 mmol/L (OR, 4.708; 95% CI, 1.640 to 13.517; P = 0.004), irregular plaque (OR, 4.017; 95% CI, 1.250 to 12.910; P = 0.020), and white thrombus (OR, 4.594; 95% CI, 1.141 to 18.487; P = 0.032). The corresponding score of three items produced a scale with good discrimination (AUC, 0.768; 95% CI, 0.665 to 0.871). The optimal cutoff value of the scale was 1.5 points with 59.4% sensitivity and 84.5% specificity. Conclusion: The three-item scale comprising HDL-C <0.925 mmol/L, angiographical irregular plaque, and white thrombus detected by OCT may provide information to identify symptomatic carotid plaque. Further large-scale studies are required to validate whether the symptomatic carotid plaque scale is clinically valuable in recognizing carotid atherosclerosis in the early stages.