Association of Mismatch Profiles and Clinical Outcome from Endovascular Therapy in Large Infarct: A Post-Hoc Analysis of the ANGEL-ASPECT Trial.

OBJECTIVES: We investigated whether patients with large infarct and the presence or absence of perfusion mismatch are associated with endovascular treatment benefit. METHODS: This is a post-hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct (ANGEL-ASPECT) randomized trial, which enrolled patients within 24 hours of onset with ASPECTS 3 to 5 or ASPECTS 0 to 2 with an infarct core 70 to 100 ml. Mismatch ratio was defined as time-to-maximum (Tmax) >6 s cerebral volume/ischemic core volume, and mismatch volume was defined as Tmax >6 s volume minus ischemic core volume. We divided patients into mismatch ratio ≥1.2 and mismatch volume ≥10 ml, and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups. The primary outcome was the 90-day modified Rankin Scale score ordinal distribution. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: There were 425 patients included. In both the mismatch ratio ≥1.2 and mismatch volume ≥10 ml (mismatch+, n = 395; mismatch-, n = 31) and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups (mismatch+, n = 346; mismatch-, n = 80), better 90-day modified Rankin Scale outcomes were found in the endovascular treatment group compared with the MM group (4 [2-5] vs 4 [3-5], common odds ratio [cOR], 1.9, 95% confidence interval [CI] 1.3-2.7, p = 0.001; 4 [2-5] vs 4 [3-5], cOR, 1.9, 95% CI 1.3-2.8, p = 0.001, respectively), but not in patients without mismatch ratio ≥1.2 and mismatch volume ≥10 ml (5 [3-6] vs 5 [4-6], cOR, 1.2, 95% CI 0.3-4.1, p = 0.83), and mismatch ratio ≥1.8 and mismatch volume ≥15 ml (4 [3-6] vs 5 [3-6], cOR, 1.2, 95% CI 0.6-2.7, p = 0.60). However, no interaction effect was found in both subgroups (p interaction >0.10). CONCLUSION: Endovascular treatment was more efficacious than MM in patients with mismatch profiles, but no treatment effect or interaction was noted in the no mismatch profile patients. However, the small sample size of patients with no mismatch may have underpowered our analysis. A pooled analysis of large core trials stratified by mismatch is warranted. ANN NEUROL 2024.

Impact of first pass effect in endovascular treatment of large core stroke: a post-hoc analysis of the ANGEL-ASPECT trial.

BACKGROUND: The first-pass effect (FPE) is linked to better safety and efficacy prognosis in patients with small- to- moderate sized ischemic infarctions. We evaluated the incidence, prognosis, and predictors of FPE in patients with large core infarctions (LCIs). METHODS: We conducted a post-hoc analysis of data from the Trial of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT). The FPE was defined as a successful recanalization (expanded Thrombolysis in Cerebral Infarction (eTICI) 2 c/3, and eTICI 2b-3 as modified FPE (mFPE)) after one pass. The primary outcome was clinical functional independence, and the secondary outcomes were independent ambulation, assessed by the modified Rankin Scale (mRS) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) defined by the Heidelberg bleeding classification, any intracranial hemorrhage (ICH), and death within 90 days of stroke onset. RESULTS: Of the 226 patients in the study, FPE and mFPE were achieved in 33 (14.6%) and 82 (36.3%) patients, respectively. Patients with FPE exhibited shorter onset-to-puncture times (adjusted odds ratio [OR] 0.915; 95% confidence interval [CI]: 0.84 to 0.996), and patients with mFPE were older (OR 1.039; 95% CI: 1.005 to 1.075). mFPE was significantly associated with favorable outcomes (modified Rankin score [mRS] 0-2: OR 2.64; 95% CI: 1.37 to 5.07; mRS 0-3: OR 3.31; 95% CI: 1.73 to 6.33). FPE tended to improve outcomes (mRS 0-3: OR 2.24; 95% CI: 0.92 to 4.97; p=0.08). ICH rates (OR 0.60; 95% CI: 0.34 to 1.05; p=0.07) and 90-day deaths (OR 0.57; 95% CI: 0.30 to 1.09; p=0.09) tended to decrease in patients who achieved mFPE but not in patients who achieved FPE. CONCLUSIONS: In the ANGEL-ASPECT trial, patients who achieved mFPE had a higher rate of independent ambulation and functional independence, and the rates of any ICH and 90-day death tended to decrease.

Insulin Resistance and White Matter Microstructural Abnormalities in Nondiabetic Adult: A Population-Based Study.

BACKGROUND: Insulin resistance (IR) is of growing concern yet its association with white matter integrity remains controversial. We aimed to investigate the association between IR and white matter integrity in nondiabetic adults. METHODS: This cross-sectional analysis was conducted based on the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study. A total of 1709 Nondiabetic community-dwelling adults with available diffusion weighted imaging based on brain magnetic resonance imaging and completed oral glucose tolerance test were included. IR was measured non-invasively by insulin sensitivity indices (ISI), including ISIcomposite and ISI0,120, as well as homeostasis model assessment of insulin resistance (HOMA-IR). White matter microstructure abnormalities were identified by diffusion weighted imaging along with tract-based spatial statistics analysis to compare diffusion metrics between groups. The multivariable linear regression models were applied to measure the association between white matter microstructure abnormalities and IR. RESULTS: A total of 1709 nondiabetic individuals with a mean age of 60.8±6.4 years and 53.5% female were included. We found that IR was associated with a significant increase in mean diffusivity, axial diffusivity, and radial diffusivity extensively in cerebral white matter in regions such as the anterior corona radiata, superior corona radiata, anterior limb of internal capsule, external capsule, and body of corpus callosum. The pattern of associations was more marked for ISIcomposite and ISI0,120. However, the effect of insulin resistance on white matter integrity was attenuated after additionally adjustment for history of hypertension and cardiovascular disease and antihypertensive medication use. CONCLUSION: Our findings indicate a significant association between IR and white matter microstructural abnormalities in nondiabetic middle-aged community residents, while these associations were greatly influenced by the history of hypertension and cardiovascular disease, and antihypertensive medication use. Further investigation is needed to clarify the role of IR in white matter integrity, whereas prophylactic strategies of maintaining a low IR status may ameliorate disturbances in white matter integrity.

Tenecteplase versus alteplase for acute ischaemic stroke in the elderly patients: a post hoc analysis of the TRACE-2 trial.

BACKGROUND: The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke (AIS) is uncertain. We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged ≥80 years. METHODS: We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial, a randomised, phase 3, non-inferiority clinical trial. Disabling AIS patients aged ≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Symptomatic intracranial haemorrhage (sICH) within 36 hours was the safety outcome. RESULTS: Of 137 participants, mRS 0-1 at 90 days occurred in 37 (49.3%) of 75 in the tenecteplase group vs 20 (33.9%) of 59 in the alteplase group (risk ratio (RR) 1.47, 95% CI 0.96 to 2.23). sICH within 36 hours was observed in 3 (4.0%) of 76 in the tenecteplase group and two (3.3%) of 61 in the alteplase group (RR 1.30, 95% CI 0.20 to 8.41). CONCLUSIONS: The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients, which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.

Associations of life's essential 8 with extent of multi-territorial atherosclerotic plaques and stenosis: a cross-sectional study.

BACKGROUND: Life's Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. METHODS: Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (< 60), moderate (60-<80), and high (≥ 80) groups. Vascular magnetic resonance imaging was used to evaluate intracranial and extracranial arteries; thoracoabdominal computed tomography angiography to evaluate coronary, subclavian, aorta, renal, ilio-femoral arteries; and ankle-brachial index to evaluate peripheral arteries. The presence of atherosclerotic plaque or stenosis in any territory was defined as plaque or vascular stenosis with 1 territory affected or more in these arteries. The extent of atherosclerotic plaques or stenosis was assessed according to the number of these 8 vascular sites affected, and graded as four grades (none, single territory, 2-3 territories, 4-8 territories). RESULTS: Of 3065 included participants, the average age was 61.2 ± 6.7 years, and 53.5% were women (n = 1639). The moderate and high overall LE8 groups were associated with lower extent of multi-territorial plaques [common odds ratio (cOR) 0.44, 95% confidence interval (CI), 0.35-0.55; cOR 0.16, 95%CI, 0.12-0.21; respectively] and stenosis (cOR 0.51, 95%CI, 0.42-0.62; cOR 0.16, 95%CI, 0.12-0.21; respectively) after adjustment for potential covariates. Similar results were observed for medical LE8 score with the extent of multi-territorial plaques and stenosis (P < 0.05). We also found the association between behavior LE8 score and the extent of multi-territorial stenosis (P < 0.05). CONCLUSIONS: The higher LE8 scores, indicating healthier lifestyle, were associated with lower presence and extent of atherosclerotic plaque and stenosis in southern Chinese adults. Prospective studies are needed to further validate these findings.

Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT.

BACKGROUND AND PURPOSE: The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions. METHODS: In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes. RESULTS: 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54). CONCLUSIONS: Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

Inflammation and Adverse Outcomes in Patients With Acute Ischemic Stroke With and Without Chronic Kidney Disease.

BACKGROUND: Elevated white blood cell count, fibrinogen levels, and lower levels of albumin signify higher systemic inflammatory response, hypercoagulable state, and poorer nutritional status, respectively. However, a consistent conclusion could not be drawn on whether the association between inflammatory markers and cardiovascular disease was affected by the presence of chronic kidney disease (CKD). We aimed to explore the association between inflammation and adverse outcomes in patients with acute ischemic stroke (AIS), as well as whether this association differs due to the presence of CKD. METHODS AND RESULTS: This research was based on the Third China National Stroke Registry. The main adverse outcomes were poor functional outcome, stroke recurrence, and combined vascular event after 1 year. Inflammation was defined as the worst quartile of at least 2 of the aforementioned 3 markers. Finally, 8493 patients with AIS were enrolled in this study. The adjusted odds ratios/hazard ratios and 95% CIs of inflammation were 1.58 (1.34-1.86) for poor functional outcomes, 1.25 (1.06-1.47) for stroke recurrence, and 1.25 (1.06-1.46) for combined vascular event. The association between inflammation and adverse outcomes existed only in patients with AIS without CKD, although the interaction between CKD and inflammation was not statistically significant. (P for interaction >0.05). CONCLUSIONS: Inflammation, which was defined as a combination of fibrinogen, white blood cell count, and albumin, was associated with all 1-year adverse outcomes among patients with AIS. Routine assessment of these biomarkers could become a potential part of the clinical evaluation for patients with AIS, especially those without CKD, aiding clinicians in risk stratification and treatment decision-making.

Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

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.

Association of Mean Upper Cervical Spinal Cord Cross-Sectional Area With Cerebral Small Vessel Disease: A Community-Based Cohort Study.

BACKGROUND: The purpose of this study was to investigate the association between the mean upper cervical spinal cord cross-sectional area (MUCCA) and the risk and severity of cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents in Lishui City, China, from the cross-sectional survey in the PRECISE cohort study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) conducted from 2017 to 2019. We included 1644 of 3067 community-dwelling adults in the PRECISE study after excluding those with incorrect, incomplete, insufficient, or missing clinical or imaging data. Total and modified total CSVD scores, as well as magnetic resonance imaging features, including white matter hyperintensity, lacunes, cerebral microbleeds, enlarged perivascular spaces, and brain atrophy, were assessed at the baseline. The Spinal Cord Toolbox was used to measure the upper cervical spinal cord cross-sectional area of the C1 to C3 segments of the spinal cord and its average value was taken as MUCCA. Participants were divided into 4 groups according to quartiles of MUCCA. Associations were analyzed using linear regression models adjusted for age, sex, current smoking and drinking, medical history, intracranial volume, and total cortical volume. RESULTS: The means±SD age of the participants was 61.4±6.5 years, and 635 of 1644 participants (38.6%) were men. The MUCCA was smaller in patients with CSVD than those without CSVD. Using the total CSVD score as a criterion, the MUCCA was 61.78±6.12 cm2 in 504 of 1644 participants with CSVD and 62.74±5.94 cm2 in 1140 of 1644 participants without CSVD. Using the modified total CSVD score, the MUCCA was 61.81±6.04 cm2 in 699 of 1644 participants with CSVD and 62.91±5.94 cm2 in 945 of 1644 without CSVD. There were statistical differences between the 2 groups after adjusting for covariates in 3 models. The MUCCA was negatively associated with the total and modified total CSVD scores (adjusted ß value, -0.009 [95% CI, -0.01 to -0.003] and -0.007 [95% CI, -0.01 to -0.0006]) after adjustment for covariates. Furthermore, the MUCCA was negatively associated with the white matter hyperintensity burden (adjusted ß value, -0.01 [95% CI, -0.02 to -0.003]), enlarged perivascular spaces in the basal ganglia (adjusted ß value, -0.005 [95% CI, -0.009 to -0.001]), lacunes (adjusted ß value, -0.004 [95% CI, -0.007 to -0.0007]), and brain atrophy (adjusted ß value, -0.009 [95% CI, -0.01 to -0.004]). CONCLUSIONS: The MUCCA and CSVD were correlated. Spinal cord atrophy may serve as an imaging marker for CSVD; thus, small vessel disease may involve the spinal cord in addition to being intracranial.

High-Sensitivity C-reactive Protein and Intracranial Arterial Stenosis Predicted Recurrent Stroke and Dependence or Death in Minor Stroke or Transient Ischemic Attack.

AIMS: Inflammation is associated with vascular events. We aimed to investigate the relationship between high-sensitivity C-reactive protein (hsCRP) levels with and without intracranial arterial stenosis (ICAS) and the prognosis of patients with minor stroke or transient ischemic attack. METHODS: We used data from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events trial (derivation cohort) and the Third China National Stroke Registry (validation cohort). Patients were divided into four groups according to the dichotomy of hsCRP level and ICAS status. The primary outcome was new ischemic stroke within 90 days, and the secondary outcome was dependence or death (Modified Rankin Scale score of 3-6) at 90 days. The associations between hsCRP level with and without ICAS and risk of outcomes were analyzed using multivariate Cox regression and logistic regression models. RESULTS: In the derivation cohort, compared with patients with nonelevated hsCRP levels and no ICAS, those with both elevated hsCRP levels and ICAS had increased risk of recurrent stroke (adjusted hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.28-5.34; p=0.008) and dependence or death (adjusted odds ratio [OR], 7.58; 95% CI, 1.30-44.13; p=0.02). Consistent relationships of elevated hsCRP levels and presence of ICAS with recurrent stroke (adjusted HR, 1.67; 95% CI, 1.13-2.45; p=0.009) and dependence or death (adjusted OR, 1.87; 95% CI, 1.23-2.84; p=0.003) were observed in the validation cohort. CONCLUSION: Concomitant presence of increased hsCRP levels and ICAS was associated with increased risk of stroke recurrence and dependence or death in patients with minor ischemic stroke or transient ischemic attack.

In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes.

INTRODUCTION: It remains unclear whether enlarged perivascular spaces (EPVS) predict poor clinical outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attack (TIA). METHOD: Data were obtained from the Third China National Stroke Registry study. We estimated EPVS in basal ganglia (BG) and centrum semiovale (CSO) using a semiquantified scale (Grade from 0 to 4). Using Cox and logistic regression analyses, the associations of EPVS with 3-month and 1-year adverse outcomes (including recurrent stroke, ischaemic stroke, haemorrhagic stroke, combined vascular event, disability and mortality) were explored. Sensitivity analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion (SAO) were conducted. RESULT: Among 12 603 patients with AIS/TIA, median age was 61.7±11.6 years, and 68.2% were men. After adjusting for all potential confounders, frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke (HR 0.71, 95% CI 0.55 to 0.92, p=0.01) but an increased risk of haemorrhagic stroke (HR 1.99, 95% CI 1.11 to 3.58, p=0.02) at 1 year after AIS/TIA, compared with none-to-mild BG-EPVS. Patients with frequent-to-severe CSO-EPVS had a decreased risk of disability (OR 0.76, 95% CI 0.62 to 0.92, p=0.004) and all-cause death (HR 0.55, 95% CI 0.31 to 0.98, p=0.04) within 3-month but not 1-year follow-ups, compared with those with none-to-mild BG-EPVS. Sensitivity analyses showed that both BG-EPVS (HR 0.43, 95% CI 0.21 to 0.87, p=0.02) and CSO-EPVS (HR 0.58, 95% CI 0.35 to 0.95, p=0.03) were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year follow-up. CONCLUSION: BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 year. Therefore, caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

Alberta Stroke Program Early Computed Tomography Score, Infarct Core Volume, and Endovascular Therapy Outcomes in Patients With Large Infarct: A Secondary Analysis of the ANGEL-ASPECT Trial.

Importance: Endovascular therapy (EVT) demonstrated better outcomes compared with medical management in recent randomized clinical trials (RCTs) of patients with large infarct. Objective: To compare outcomes of EVT vs medical management across different strata of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and infarct core volume in patients with large infarct. Design, Setting, and Participants: This prespecified secondary analysis of subgroups of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) RCT included patients from 46 stroke centers across China between October 2, 2020, and May 18, 2022. Participants were enrolled within 24 hours of symptom onset and had ASPECTS of 3 to 5 or 0 to 2 and infarct core volume of 70 to 100 mL. Patients were divided into 3 groups: ASPECTS of 3 to 5 with infarct core volume less than 70 mL, ASPECTS of 3 to 5 with infarct core volume of 70 mL or greater, and ASPECTS of 0 to 2. Interventions: Endovascular therapy or medical management. Main Outcomes and Measures: The primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. Results: There were 455 patients in the trial; median age was 68 years (IQR, 60-73 years), and 279 (61.3%) were male. The treatment effect did not vary significantly across the 3 baseline imaging subgroups (P = .95 for interaction). The generalized odds ratio for the shift in the 90-day mRS distribution toward better outcomes with EVT vs medical management was 1.40 (95% CI, 1.06-1.85; P = .01) in patients with ASPECTS of 3 to 5 and infarct core volume less than 70 mL, 1.22 (95% CI, 0.81-1.83; P = .23) in patients with ASPECTS of 3 to 5 and infarct core volume of 70 mL or greater, and 1.59 (95% CI, 0.89-2.86; P = .09) in patients with ASPECTS of 0 to 2. Conclusions and Relevance: In this study, no significant interaction was found between baseline imaging status and the benefit of EVT compared with medical management in patients with large infarct core volume. However, estimates within subgroups were underpowered. A pooled analysis of large core trials stratified by ASPECTS and infarct core volume strata is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04551664.

Association of metabolic dysfunction-associated fatty liver disease with systemic atherosclerosis: a community-based cross-sectional study.

BACKGROUND: Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). METHODS: In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. RESULTS: This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85-2.48) and stenosis (cOR, 1.47, 95% CI 1.26-1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24-1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P < 0.05). However, lean-MAFLD was only associated with the extent of atherosclerotic plaques (cOR, 1.63, 95% CI 1.14-2.34). As one component of MAFLD, FLD per se was associated with the extent of plaques and stenosis in participants with MAFLD. Furthermore, FLD interacted with MD to increase the odds of presence of systemic atherosclerosis (P for interaction ≤ 0.055). CONCLUSIONS: MAFLD and its subtypes of DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD. This study implicated that FLD might be a potential target of intervention for reducing the deleterious effects of MAFLD on systemic atherosclerosis.

Optimal systolic and diastolic blood pressure threshold that associated with lower risk of white matter hyperintensity progression.

Background: The optimal control thresholds for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with white matter hyperintensity (WMH) are still unclear. Method: A longitudinal retrospective study of patients with brain magnetic resonance imaging (MRI) scans with intervals of more than 3 years was conducted. Blood pressure records during hospitalization and from outpatient visits between baseline and the last MRI scan were collected. The outcome was the change in total WMH from baseline to the final visit. Results: Among the 965 patients with MRI scans, 457 patients with detailed longitudinal blood pressure records were ultimately included and classified into the WMH absent group (n = 121), mild WMH group (n = 126), and moderate to severe WMH group (n = 210). Both baseline and longitudinal mean SBP, DBP, and SBP SD were significantly associated with WMH severity (p < 0.05). An average SBP of 130-140 mmHg [vs. <130 mmHg, aOR, 1.80, (95% CI, 1.05-3.07), p = 0.03] was associated with a higher risk of WMH progression. DBP ≥ 90 mmHg [vs. <80 mmHg, OR, 1.81, (95% CI, 0.88-3.74), p = 0.02, aOR, 1.54, (95% CI, 0.66-3.53), p = 0.32] was associated with a higher risk of WMH progression, but was not after adjusted for other covariates. Longitudinal BP variability was not significantly associated with WMH progression. Conclusion: Both SBP and DBP had a stronger relationship with the severity of WMH. A target mean SBP of <130 mmHg and mean DBP of <80 mmHg was associated with a lower risk of WMH progression.

Predicting internalizing symptoms with machine learning: identifying individuals that need care.

Objective The current project aims to identify individuals in urgent need of mental health care, using a machine learning algorithm (random forest). Comparison/contrast with conventional regression analyses is discussed. Participants: A total of 2,409 participants were recruited from an anonymous university, including undergraduate and graduate students, faculty, and staff. Methods: Answers to a COVID-19 impact survey, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) were collected. The total scores of PHQ-9 and GAD-7 were regressed on six composites that were created from the questionnaire items, based on their topics. A random forest was trained and validated. Results: Results indicate that the random forest model was able to make accurate, prospective predictions (R2 = .429 on average) and we review variables that were deemed predictively relevant. Conclusions: Overall, the study suggests that predictive models can be clinically useful in identifying individuals with internalizing symptoms based on daily life disruption experiences.

Association between Fibrinogen-to-Albumin Ratio and Adverse Stroke Outcomes among Patients with Acute Ischemic Stroke.

INTRODUCTION: Fibrinogen-to-albumin ratio (FAR) is implicated in prothrombotic states and is associated with an increased risk of acute ischemic stroke (AIS). However, studies investigating whether the prothrombotic effect of FAR is associated with long-term adverse outcomes in patients with AIS are lacking. Therefore, we aimed to investigate the association based on The Third China National Stroke Registry (CNSR-III). METHODS: Patients with AIS with complete laboratory data for fibrinogen and albumin in the CNRS-III were included in this study. The primary outcomes were poor functional outcomes (modified Rankin scale score 3-6) at 12 months, including disability (modified Rankin scale score 3-5), all-cause death, recurrent stroke, and combined vascular events within 1 year. Univariate and multivariate logistic or Cox regression analyses were used to investigate the association between FAR quartiles and adverse outcomes. RESULTS: A total of 8984 patients with AIS were enrolled in this study. After one-year follow-up, 238 patients were lost to follow-up. A total of 1230(14.06%) patients had poor functional outcomes; 932(10.37%) and 981(10.92%) experienced stroke recurrence and combined vascular events, respectively. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the highest quartile of the FAR(>11.44) were 1.64(1.35-2.00) for poor functional outcomes, 1.68(1.34-2.10) for disability, 1.40(1.02-1.94) for all-cause death, 1.11(0.92-1.34) for stroke recurrence, and 1.11(0.92-1.33) for combined vascular event, respectively. CONCLUSION: High FAR(>11.44) increased the risk of short- and long-term poor functional outcomes, including disability and all-cause death among patients with AIS. The FAR may play an important role in the early stratification of patients with AIS.

Association between Life's Essential 8 and Cerebral Small Vessel Disease.

BACKGROUND: Given that associations of Life's Essential 8 (LE8) and cerebral small vessel disease (CSVD) or its imaging markers were unclear, we examined relationship between them. METHODS: The cross-sectional study included community residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. We calculated the total LE8 score, medical LE8 score and behavioural score, and categorised them into low (<60), moderate (60-79) or high (≥80) group. MRI markers included lacunes, white matter hyperintensities (WMH), enlarged perivascular spaces in basal ganglia (BG-EPVS) and cerebral microbleeds (CMB). In respect of, total CSVD score (0-4 points), WMH, lacunes or CMB were categorised as two grades, and BG-EPVS (N>10) was allocated one point. Based on modified total CSVD score (0-6 points), WMH or CMB was modified to three grades, and BG-EPVS (N>20) was allocated one point. RESULTS: Among 3061 participants in this study, 1424 (46.5%) were male. Higher LE8 score was associated with lower total CSVD score (moderate vs low: cOR 0.78, 95% CI 0.63 to 0.96; high vs low: cOR 0.44, 95% CI 0.33 to 0.59), and the medical score was inversely related to the total CSVD score. Furthermore, the medical score was inversely related to odds of WMH (p<0.05), modified WMH (p<0.05), lacunes (p<0.05) or BG-EPVS (p<0.05), and the behavioural score were inversely related to the odds of lacunes and BG-EPVS. CONCLUSIONS: Higher LE8 score which indicates better cardiovascular status was associated with lower burden of CSVD and its MRI markers. Longitudinal studies are needed to examine the causality.

Comparison of masticatory myofunctional rehabilitation combined with conventional functional appliances for the treatment of class â ¡, division 1 malocclusion. A retrospective cohort study.

OBJECTIVE: To estimate the clinical efficacy of early masticatory myofunction rehabilitation combined with conventional functional appliances for the treatment of class Ⅱ, division 1 malocclusion in orthodontic children during the growing phase. MATERIALS AND METHOD: A comparative retrospective cohort study, enrolled patients diagnosed with class Ⅱ/1 in the stage of late mixed or early permanent dentition. Patients were divided into a TBA group (Cohort 1): receiving Twin-block appliance treatment; and a MMR group (Cohort 2): receiving either early masticatory myofunction rehabilitation as adjunctive therapy combined with the same conventional functional appliances. The study variables were active (Phase 1) treatment duration, oral esthetic subjective impact score (OASIS), several cephalometric indices calculated from X-ray photographs, the maximum voltage (mV) and asymmetry index (AsI) of anterior temporalis (TA) and masseter muscles (MM) before and after treatment. Complications were also recorded. RESULTS: A total of 424 cases were enrolled. The mean treatment duration in the MMR group was 168.33 days (SD: 25.43) and 215.00 days (SD: 28.81) in the TBA group; mean difference: -46.67 days (95% CI: [-81.62, -11.71]), P<0.001. For the OASIS outcome measure, there was no statistically significant difference between the mean total scores for the MMR group (18.83±7.73) or TBA group (17.67±6.47) groups adjusted to include pre-treatment OASIS scores (P = 0.783). After treatment, sella-nasion-B point (SNB), mandibular incisor angle, maxillary base and mandibular base in both two groups were significantly increased, while AB plane angle (ANB), maxillary incisor angle, overjet and overbite were significantly decreased. The mV and AsI of TA and MM were also improved following treatment. However, no significant differences were observed between two groups. CONCLUSION: Our results confirmed that early masticatory myofunction rehabilitation in combination with conventional TBA for patients in the growing phase was significantly effective in the management of class Ⅱ/1 in orthodontic treatment, which could significantly shorten the treatment duration and had the similar improvement in the cephalometry data, OASIS scores and masticatory muscles function when comparing to conventional TBA alone.

The Association Between the Fibrinogen-to-Albumin Ratio and Intracranial Arterial Stenosis in Patients With Acute Ischemic Stroke.

The association between the fibrinogen-to-albumin ratio (FAR) and intracranial arterial stenosis (ICAS) in patients with acute ischemic stroke (AIS) has not yet been reported. In this large-scale investigation, 7894 AIS patients with ICAS-evaluation imaging data from the Third China National Stroke Registry were included. ICAS was defined as >50% stenosis of the intracranial arteries. We dichotomized the degree of ICAS into stenosis and occlusion. The number of ICAS lesions was the total number of intracranial stenotic arteries. Fibrinogen and albumin levels were assessed in the central laboratory of Beijing Tiantan Hospital. Univariate and multivariate analyses with logistic regression were used to determine the association between the FAR quartiles and ICAS. A total of 3900 (49.66%) patients had ICAS. Compared with those of the lowest FAR quartile, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the highest FAR quartile were 1.26 (1.10-1.44), 1.15 (.99-1.33), and 1.19 (1.01-1.39) for ICAS, symptomatic ICAS, and asymptomatic ICAS, respectively. An elevated FAR was also associated with occlusion (adjusted OR: 1.28, 95% CI: 1.10-1.49) and lesion number ≥2 (adjusted OR: 1.25, 95% CI: 1.07-1.45).