Effect of Time Window on Endovascular Thrombectomy with or without Intravenous Thrombolysis in Acute Ischemic Stroke: Results from DIRECT-MT.

INTRODUCTION: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. METHODS: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h. RESULTS: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. CONCLUSIONS: Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.

Colloidal crystals array enabled bionic biliary stent for efficient domestic biofluid management.

In vivo surgical interventions require effective management of biofluids, including controlling bleeding and removing excess biofluids such as bile, wound exudate, and blood. To address these issues, recent advances have emerged, such as self-sealing needles, drug-eluting stents, and shear-thinning hydrogels. However, complications associated with intestinal mucosal injury and secondary damage still persist. Therefore, a multifunctional stent is urgently required that can effectively remove excessive biofluid. Surface wettability of biliary stents is crucial in biofluid management, and conventional coatings can cause adhesion to wound tissue. To overcome this issue, we developed an interpenetrating Janus wettability stent coating, enabling unidirectional draining of excessive biofluid from its hydrophobic side to hydrophilic side, thereby preventing biofluid from wetting the wound. Furthermore, we demonstrate a directional biofluid movement using a self-pumping dressing in an infected tissue model, providing a new approach for in situ biofluid collection and disease diagnosis by detecting metal ion changes. Overall, our integrated system presents an opportunity to design wound dressings with effective biofluid management and metal ion detection capabilities.

Percutaneous angioplasty and/or stenting versus aggressive medical therapy in patients with symptomatic intracranial atherosclerotic stenosis: a 1-year follow-up study.

Background: Symptomatic intracranial atherosclerotic stenosis (sICAS) is one of the common causes of ischemic stroke. However, the treatment of sICAS remains a challenge in the past with unfavorable findings. The purpose of this study was to explore the effect of stenting versus aggressive medical management on preventing recurrent stroke in patients with sICAS. Methods: We prospectively collected the clinical information of patients with sICAS who underwent percutaneous angioplasty and/or stenting (PTAS) or aggressive medical therapy from March 2020 to February 2022. Propensity score matching (PSM) was employed to ensure well-balanced characteristics of two groups. The primary outcome endpoint was defined as recurrent stroke or transient ischemic attack (TIA) within 1 year. Results: We enrolled 207 patients (51 in the PTAS and 156 in the aggressive medical groups) with sICAS. No significant difference was found between PTAS group and aggressive medical group for the risk of stroke or TIA in the same territory beyond 30 days through 6 months (P = 0.570) and beyond 30 days through 1 year (P = 0.739) except for within 30 days (P = 0.003). Furthermore, none showed a significant difference for disabling stroke, death and intracranial hemorrhage within 1 year. These results remain stable after adjustment. After PSM, all the outcomes have no significant difference between these two groups. Conclusion: The PTAS has similar treatment outcomes compared with aggressive medical therapy in patients with sICAS across 1-year follow-up.

Higher Serum E-Selectin Levels Associated with Malignant Brain Edema after Endovascular Thrombectomy for Ischemic Stroke: A Pilot Study.

Background and Purpose: Little is known about the effect of soluble adhesion molecules on malignant brain edema (MBE) after endovascular thrombectomy (EVT). This study aimed to explore the association between serum concentrations of E-selectin and the risk of MBE in patients who received EVT. Methods: Patients with a large vessel occlusion stroke in the anterior circulation who underwent EVT were prospectively recruited. Serum soluble E-selectin concentrations were measured after admission for all patients. MBE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 h after surgery. Multivariate logistic regression analyses were performed to determine the association between E-selectin levels and the risk of MBE. Results: Among the 261 included patients (mean age, 69.7 ± 12.3 years; 166 males), 59 (22.6%) developed MBE. Increasing circulating E-selectin levels were associated with an increased risk of MBE after multivariable adjustment (odds ratios [OR], highest vs. lowest quartile: 3.593; 95% confidence interval [CI], 1.178-10.956; p = 0.025). We further observed a significantly positive association between E-selectin and MBE (per 1-standard deviation increase; OR, 1.988; 95% CI, 1.379-2.866, p = 0.001) when the E-selectin levels were analyzed as a continuous variable. Furthermore, the restricted cubic spline demonstrated a linear correlation between serum E-selectin levels and the risk of MBE (p < 0.001 for linearity). Conclusions: In this prospective study, circulating levels of E-selectin were associated with an increased risk of MBE after EVT. Further mechanistic studies are warranted to elucidate the pathophysiology underlying this association.

Endovascular treatment of acute basilar artery occlusion in patients with and without atrial fibrillation: results from the ATTENTION registry.

Background: Previous studies have shown a potential beneficial effect of endovascular therapy (EVT) in patients with acute basilar artery occlusion (BAO). It was unclear that whether atrial fibrillation (AF) can affect the clinical outcomes for BAO patients treated with EVT. Objectives: To investigate the association between AF and clinical outcomes, and whether AF can modify the efficacy and safety of EVT in patients with BAO. Design: We conducted a multicenter, nationwide, retrospective analysis to investigate how the presence of AF affects treatment allocation for BAO patients. Methods: The endovascular treatment for acute basilar artery occlusion (ATTENTION) registry was a multicenter, prospective study in China that included acute BAO patients who underwent EVT or received best medical management (BMM) between 2017 and 2021. The outcomes include the distribution of 3-month modified Rankin scale (mRS) score, functional independence (defined as mRS 0-3), symptomatic intracerebral hemorrhage, and mortality. Results: 2134 patients were included in the study, of which 619 had AF and 1515 did not have AF. The median age was 65 (interquartile range [IQR]: 56-73) years, and 689 (32.3%) patients were female. Multivariate regression analysis indicated no significant association existed between AF and the distribution of mRS (adjusted common odds ratio, 1.05 [95% CI: 0.88, 1.25]; p = 0.564) at 90 days. Similarly, AF was not found to have a significant association with and other measured outcomes, or with the effects of EVT in AF subgroups for at 90 days as measured by ordinal mRS (p for heterogeneity = 0.247). Finally, no significant differences were found for symptomatic intracerebral hemorrhage and mortality within 90 days between the EVT and BMM groups across AF subgroups. Conclusions: Our results illustrated that the effect of EVT did not differ statistically in acute ischemic stroke patients with and without AF. Moreover, no significant association between AF and functional or safety outcomes could be detected at 90 days.

Levels of adhesion molecules and clinical outcomes in patients with ischemic stroke after mechanical thrombectomy.

Background and purpose: Data on adhesion molecule levels in patients treated with mechanical thrombectomy (MT) are scarce. We aimed to evaluate the association among adhesion molecule levels, symptomatic intracranial hemorrhage (sICH), and clinical outcome and to determine whether the sICH influences the association of adhesion molecules with functional outcome. Methods: Patients with large artery occlusion in the anterior circulation and treated with MT were prospectively recruited. Adhesion molecules, such as soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) were tested. An unfavorable outcome was defined as a 90-day modified Rankin Scale (mRS) score of 3-6. The sICH was diagnosed according to the Heidelberg Bleeding Classification within 72 h of endovascular treatment (EVT). Results: Of the 310 enrolled patients (mean age, 68.5 years; 198 men), 46 (14.8%) experienced sICH and 173 (55.8%) experienced an unfavorable outcome at 90 days. After adjusting for potential confounders, patients with higher sVCAM-1 and sE-selectin levels had an increasing trend of sICH [4th quartile vs. 1st quartile for sVCAM-1; odds ratio (OR), 2.766, p = 0.085; sE-selectin; OR, 2.422, p = 0.086] and poor outcome (4th quartile vs. 1st quartile for sVCAM-1; OR, 2.614, p = 0.025; sE-selectin; OR, 2.325, p = 0.046). Furthermore, the sICH might partially mediate the worse functional outcome in patients with higher adhesion molecules levels (Sobel test, p < 0.001 for sVCAM-1 and p = 0.007 for sE-selectin). Conclusions: There were significant relationships between levels of adhesion molecules and a 90-day poor outcome in patients with ischemic stroke treated with MT, which was partially mediated by sICH.

Simvastatin-Loaded Lipid Emulsion Nanoparticles: Characterizations and Applications.

Simvastatin (SIM) is a diet drug to treat high lipid levels in the blood. It has the drawback of being metabolized in humans' gastrointestinal tract (GIT) when taken in an oral dosage form. To enhance the role of SIM in treating hyperlipidemias and bypassing its metabolism in GIT, a biodegradable nanocarrier as a SIM-loaded lipid emulsion nanoparticle via the solvent injection method was designed. Cholesterol acts as a lipid core, and Tween 80 was utilized to stabilize the core. The optimized nanoformulation was characterized for its particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. Furthermore, the transdermal hydrogel was characterized by physical appearance, rheology, pH, and spreadability. In vitro assays were executed to gauge the potential of LENPs and olive oil for transdermal delivery. The mean particle size and zeta potential of the optimized nanoparticles were 174 nm and -22.5 mV 0.127, respectively. Crystallinity studies and Fourier transform infrared analyses revealed no molecular interactions. Hydrogels showed a sustained release compared to SIM-loaded LENPs that can be proposed as a better delivery system for SIM. We encourage further investigations to explore the effect of reported formulations for transdermal delivery by in vivo experiments.

Endovascular Treatment Versus Best Medical Management in Acute Basilar Artery Occlusion Strokes: Results From the ATTENTION Multicenter Registry.

BACKGROUND: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). METHODS: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0-3) at 90 days. We also performed a sensitivity analysis with the propensity score matching-based and the instrumental variable-based analysis. RESULTS: In our primary analysis using the inversed probability of treatment weighting-based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19-1.65]; absolute risk difference, 11.8% [95% CI, 6.9-16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69-0.88]; absolute risk difference, -10.3% [95% CI, -15.8 to -4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching-based and instrumental variable-based analysis. CONCLUSIONS: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2000041117.

A Novel Nomogram for Predicting Prognosis after Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

BACKGROUND: Mounting evidence has shown that mechanical thrombectomy (MT) improves clinical outcomes for large vessel occlusions (LVOs) in patients with acute ischemic stroke (AIS) of the anterior circulation. The present study aimed to provide a comprehensive analysis of risk factors associated with clinical outcomes in AIS patients receiving MT. METHODS: A total of 212 consecutive patients who underwent MT for AIS were enrolled in the present study. Clinical characteristics were recorded at admission. Two endpoints were defined according to the 3-month modified Rankin scale (mRS) score after AIS (good outcome, mRS 0-2; and death, mRS 6). Additionally, we compared the clinical outcomes and safety of MT alone and bridging therapy in AIS patients. RESULTS: Of the 212 patients treated with MT, 114 (53.77%) patients had a good outcome and 31 (14.62%) died. The incidence of a worse outcome after MT was significantly elevated in males and patients with high WBC counts, high admission blood glucose levels, high baseline NIHSS scores and a long interval time from groin puncture to reperfusion in AIS patients treated with MT after adjustment for covariates (P<0.05); these risk factors were further confirmed by our constructed nomograms. In addition, we observed no significant benefit of bridging therapy compared to MT alone in AIS patients. CONCLUSION: Our constructed nomogram based on male sex, admission WBC, admission blood glucose, NIHSS, and the interval time from groin puncture to reperfusion predicts prognosis after mechanical thrombectomy in patients with acute ischemic stroke.

Endovascular treatment of acute ischemic stroke due to anterior circulation large vessel occlusion beyond 6 hours: a real-world study in China.

BACKGROUND: We aimed to assess the safety and efficacy of endovascular treatment (EVT) in patients with anterior circulation emergent large vessel occlusion (ELVO) beyond 6 h from symptom onset in a real-world cohort of patients in China. METHODS: We retrospectively examined 305 patients with anterior circulation ELVO treated with EVT. Patients were divided into two groups: treated with known onset within 6 h (n = 238) and beyond 6 h (n = 67). Multivariable logistic regression and ordinal shift analyses were used to evaluate the associations between onset-to-groin puncture time and safety and efficacy outcomes. RESULTS: Treatment beyond 6 h was not associated with symptomatic intracranial hemorrhage within 48 h (sICH; odds ratio [OR] 2.03, 95% confidence interval [CI] 0.48-8.57, p = 0.334), in-hospital mortality (OR 1.95, 95% CI 0.48-7.91, p = 0.348), successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b or 3; OR 0.73, 95% CI 0.31-1.73, p = 0.470), favorable functional outcome (modified Rankin Scale score 0-2; OR 0.55, 95% CI 0.25-1.23, p = 0.145), and functional improvement (modified Rankin Scale shift by 1-point decrease; common OR 0.80, 95%CI 0.45-1.42, p = 0.450) at 3 months compared with treatment within 6 h. Futher interaction analysis showed that stroke etiology did not modify the associations between onset-to-groin puncture time and outcomes (p > 0.05). CONCLUSIONS: In this real-world study, after careful assessment, EVT beyond 6 h from known stroke onset was safe, effective and had comparable short-term outcomes to EVT within 6 h.

The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. RESULTS: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. CONCLUSIONS: NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.

Admission blood cell counts are predictive of stroke-associated infection in acute ischemic stroke patients treated with endovascular therapy.

Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (P < 0.05). The multivariable logistic regression analyses showed that older age in addition to higher diastolic blood pressure (DBP), NIHSS score, fasting blood glucose, WBC and neutrophil counts, NLR, and PLR were significantly associated with SAI (P < 0.05). However, these associations were not revealed in 337 non-EVT AIS patients. Furthermore, based on the inflammatory markers, we developed a nomogram that provided the opportunity for more accurate predictions (compared with conventional factors) and appeared a better prognostic tool for SAI according to the decision curve analysis. In summary, if proven externally valid, our nomogram that included WBC count, NLR, and PLR may be a useful tool for SAI prediction in clinical practice.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

Effectiveness of Revive SE in the RAPID registry : Revive Acute Ischemic Stroke Patients ImmeDiately (RAPID) Prospective Multicenter Trial.

PURPOSE: The prospective, multicenter Revive Acute ischemic stroke Patients ImmeDiately (RAPID) trial was carried out to evaluate the real-world safety and efficacy of the Revive SE stent retriever. METHODS: From January 2017 the study planned to enroll 100 patients with acute ischemic stroke who were treated with the Revive SE as a first pass. The study primary outcomes were rates of favorable reperfusion using the modified thrombolysis in cerebral infarction score [mTICI] 2b/3 and rates of favorable outcome with the modified Rankin Scale (mRS) ≤2 at 3 months. The secondary outcomes were time interval from puncture to vascular reperfusion, number of passes by Revive SE stent-retriever, incidence of distal embolization and into new territories and rate of symptomatic intracranial hemorrhage (SICH) within 24 h post intervention. RESULTS: A total of 100 treated patients (mean age: 65.6 ± 11.3 years) were enrolled. The median National Institutes of Health Stroke Scale before the procedure was 16. Target vessel occlusions were as follows: middle cerebral artery (MCA) M1 in 48, M2 in 6, anterior cerebral artery (ACA) in 3, internal carotid artery (ICA) in 22, basilar artery (BA) in 17, and vertebral artery (VA) in 4. Reperfusion rate with Revive SE without rescue devices was 69%. Reperfusion rate with Revive SE only was 83.3% in MCA M2, followed by 82.4% in BA. Thromboembolic complications and SICH developed in 10% and 2% of patients, respectively. Overall, a satisfactory reperfusion was achieved in 92% and a favorable outcome at 90 days in 48%. CONCLUSION: Use of the Revive SE for thrombectomy appeared to be effective and safe but these findings need be confirmed in larger clinical trials (RAPID ClinicalTrials.gov number, NCT03007082).

Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial.

BACKGROUND: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. METHODS: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556. FINDINGS: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. INTERPRETATION: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. FUNDING: Jiangsu Provincial Special Program of Medical Science.

A prediction model of brain edema after endovascular treatment in patients with acute ischemic stroke.

BACKGROUND: Clinical tools predicting brain edema after reperfusion therapy in acute ischemic stroke are scarce. We aim to develop a nomogram model to predict brain edema within the first 24 h after endovascular treatment (EVT) in the anterior cerebral circulation. METHODS: A total of 199 patients were retrospectively identified in a single-center stroke registry. Brain edema was measured by midline shift (MLS). The associations between MLS and early neurologic outcomes were described. A nomogram predicting MLS was developed and internally validated. The nomogram was also compared with an available model using the area under the receiver operating characteristic curve (AUC) and decision curve analyses. RESULTS: Overall, 87 patients (43.7%) had MLS. The patients with MLS ≥ 6 mm showed progressive neurological deterioration according to repeated measures analysis of variance. Each millimeter increase in MLS was strongly correlated with the presence of in-hospital death or forgoing treatment (Spearman's rho = 0.429, P < .001). Patients with brain edema were less likely to have functional independence at 3 months (19.5% vs. 46.8%, P < .001). A nomogram model including 24-h CT ASPECT scores and cisternal effacement, hypertension and complete recanalization showed a C-index of 0.874. This tool exhibited a higher AUC and higher net benefit than the available model. CONCLUSIONS: This study showed a profound association between MLS and early neurologic outcomes. A nomogram model was developed to predict patients at risk of brain edema after EVT in the anterior cerebral circulation.

Low triglyceride to high-density lipoprotein cholesterol ratio predicts hemorrhagic transformation in large atherosclerotic infarction of acute ischemic stroke.

The ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) is an objective approach to predicting poor outcomes in acute ischemic stroke (AIS). The impact of TG/HDL-C on hemorrhagic transformation (HT) after AIS remains unknown. The aim of this study was to explore the accurate effect of TG/HDL-C on HT after AIS. We enrolled a total of 1423 patients with AIS in the training cohort from a prospective, consecutive hospital-based stroke registry. Of the 1423 patients, HT occurred in 155 (10.89%) patients. The incidence of HT after AIS was significantly increased when there were low levels of TG (P=0.016) and TG/HDL-C (P=0.006) in patients with AIS attributable to large artery atherosclerosis (LAA), but not in those who suffered from cardioembolic stroke. After adjustment for covariates, a lower TG/HDL-C (OR=0.53, 95%CI=0.20-0.93) that was more than TG alone (OR=0.61, 95%CI=0.27-0.98) independently increased the risk of HT in LAA. Furthermore, our established nomogram indicated that lower TG/HDL-C was an indicator of HT. These findings were further validated in the test cohort of 558 patients with AIS attributable to LAA. In summary, a low level of TG/HDL-C is correlated with greater risk of HT after AIS attributable to LAA.

Relation between lipoprotein-associated phospholipase A2 mass and incident ischemic stroke severity.

BACKGROUND: Manifestations of ischemic stroke vary widely, and serum biomarkers may be useful for stratification of risk of severe stroke. This study evaluated the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and initial severity. METHODS: We employed a retrospective analysis on our hospital-based registry and recruited 488 first-onset ischemic stroke patients admitted within 24 h after onset and with Lp-PLA2 mass measured. Stroke severities evaluated by National Institutes of Health Stroke Scale (NIHSS) were compared between Lp-PLA2 categories dichotomized by median. Multivariate logistic regression was used to detect the independent risk factors of severe stroke (NIHSS ≥ 7) and receiver operator curve (ROC) was constructed to detect the value of addition of Lp-PLA2 to the model of other risk factors for predicting severe stroke. RESULTS: Of the overall patients, the median admission NIHSS scores was 3 and 28.1% had severe manifestation. Admission NIHSS scores were different between patients of Lp-PLA2 above and under the median (median NIHSS 4 vs. 3, P < 0.001). Lp-PLA2 levels was correlated with admission NIHSS (r = 0.268, P < 0.001). Logistic regression showed Lp-PLA2 category (OR 2.37, 95%CI 1.44-3.90, P < 0.001) and levels per 100 ng/ml (OR 1.69, 95%CI 1.35-2.11, P < 0.001) were both independently associated with severe stroke. Addition of Lp-PLA2 category and levels to other independent risk factors both increased the area under curves (from 0.676 to 0.718 with category and 0.734 with levels). CONCLUSION: Lp-PLA2 was independently related to admission severity in ischemic stroke patients, implying a potential predictive value of Lp-PLA2 for severe stroke in prevention.

Acute ischemic dissection of an "S"-shaped carotid artery: The "one-stop" value of using a detachable Solitaire AB stent.

This study aimed to evaluate the efficacy and safety of endovascular repair using detachable Solitaire AB stents for acute ischemic dissection of "S"-shaped carotid arteries. From May 2015 to December 2016, a total of 127 patients with acute ischemic stroke (AIS) underwent endovascular treatment in our center. Among them, five AISs were due to acute dissection of an "S"-shaped carotid artery. Coexisting carotid embolism was identified in all five patients, who first underwent successful Solitaire AB stent-based retrieval of the embolism. All patients then underwent Solitaire AB stenting to reopen the occluded carotid arteries, all of which were successfully recanalized. There were no procedure-related complications, except for minor hemorrhage transformation in one patient. The mean NIHSS scores were 12 ±â€¯3.7 and 3.8 ±â€¯3.4 at admission and 90 days after stenting, respectively (P = 0.018). The median modified Rankin Scale score at 90 days was 2.0 ±â€¯1.4. Follow-up computed tomography angiography demonstrated in-stent patency in four of the five patients. Dissection of an "S"-shaped carotid artery infrequently leads to AIS. Such dissected arteries can be safely and reliably repaired by this stenting, ensuring successful reconstruction of the carotid arterial circulation.

Carotid Endarterectomy and Carotid Artery Stenting Lead to Improved Cognitive Performance in Patients with Severe Carotid Artery Stenosis.

In patients with severe carotid artery stenosis, the effects of carotid artery reopening, achieved either by carotid endarterectomy (CEA) or carotid artery stenting (CAS), on cognitive functions remain elusive. Herein, we conducted a prospective study to determine whether and to what extent CEA and CAS affected cognitive performance. Patients admitted to the Department of Neurology or Vascular Surgery in Nanjing First Hospital from December 2012 to March 2015 with a diagnosis of severe carotid artery stenosis (>70%) were included in the study. Among them, 77 patients underwent CEA, 81 patients underwent CAS, and 77 patients who refused to receive aforementioned interventions were enrolled in control group. Of note, all patients in this study received basic pharmacological treatment according to the American Heart Association/American Stroke Association guidelines. Cognitive functions were evaluated by a broad spectrum of neuropsychological tests including the Mini-mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and event related potential P300 on the day prior to and at 3 months after indicated intervention. When compared with basic pharmacological treatment, both CEA and CAS significantly increased the scores of MMSE and MoCA at 3 months following procedures. Meanwhile, a significant reduction of P300 score was also observed in patients underwent CEA or CAS. In addition, the changes in MMSE, MoCA and P300 scores over time between CEA and CAS groups were not statistically significant. Taken together, our findings suggest an improvement of cognitive functions following carotid artery reopening. Meanwhile, the beneficial effects of CEA and CAS on cognitive performance seem to be equivalent.