Delayed Stroke Treatment during COVID-19 Pandemic in China.

BACKGROUND: Social distance, quarantine, pathogen testing, and other preventive strategies implemented during CO-VID-19 pandemic may negatively influence the management of acute ischemic stroke (AIS). OBJECTIVE: The current study aimed to evaluate the impacts of COVID-19 pandemic on treatment delay of AIS in China. METHODS: This study included patients with AIS admitted in 2 hospitals in Jiangsu, China. Patients admitted before and after the COVID-19 pandemic outbreak (January 31, 2020, as officially announced by the Chinese government) were screened to collect sociodemographic data, medical history information, and symptom onset status from clinical medical records and compared for pre- (measured as onset-to-door time [ODT]) and posthospital delay (measured as door-to-needle time [DNT]). The influencing factors for delayed treatment (indicated as onset-to-needle time >4.5 h) were analyzed with multivariate logistic regression analysis. RESULTS: A total of 252 patients were included, of which 153 (60.7%) were enrolled before and 99 (39.3%) after the COVID-19 pandemic. ODT increased from 202 min (interquartile range [IQR] 65-492) before to 317 min (IQR 75-790) after the COVID-19 pandemic (p = 0.001). DNT increased from 50 min (IQR 40-75) before to 65 min (IQR 48-84) after the COVID-19 pandemic (p = 0.048). The proportion of patients with intravenous thrombolysis in those with AIS was decreased significantly after the pandemic (15.4% vs. 20.1%; p = 0.030). Multivariate logistic regression analysis indicated that patients after COVID-19 pandemic, lower educational level, rural residency, mild symptoms, small artery occlusion, and transported by other means than ambulance were associated with delayed treatment. CONCLUSIONS: COVID-19 pandemic has remarkable impacts on the management of AIS. Both pre- and posthospital delays were prolonged significantly, and proportion of patients arrived within the 4.5-h time window for intravenous thrombolysis treatment was decreased. Given that anti-COVID-19 measures are becoming medical routines, efforts are warranted to shorten the delay so that the outcomes of stroke could be improved.

Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial.

Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. Design, Setting, and Participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. Main Outcomes and Measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%). Conclusions and Relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.

Intravenous Thrombolysis before Thrombectomy may Increase the Incidence of Intracranial Hemorrhage inTreating Carotid T Occlusion.

BACKGROUND AND PURPOSE: Current evidence does not agree on the merits of direct and bridging thrombectomy. This study aimed to compare the safety and efficacy of direct thrombectomy (DT) and bridging thrombectomy (BT) in treating patients with acute ischaemic stroke due to carotid T occlusion. METHODS: Patients with stroke due to carotid T occlusion who were treated with DT or BT were retrospectively collected from four advanced stroke centres. Baseline characteristics and clinical outcomes were compared between the groups. Successful recanalization was defined by a modified thrombolysis in cerebral infarction (mTICI) score of 2b or 3. A favourable outcome was defined by a modified Rankin Scale (mRS) score of 0-2 at 90 days after stroke onset. Multivariable analysis was performed to control for potential confounders. RESULTS: Of the 111 enrolled patients, 57 (51.4%) patients were treated with DT, and 54 (48.6%) were treated with BT. Patients treated with DT had a shorter imaging to puncture (ITP) time (53 min versus 92 min, P<0.001) and symptom onset to puncture (OTP) time (198 min versus 218 min, P=0.045) than patients treated with BT. No significant difference was detected concerning the rate of successful recanalization (80.7% versus 77.8%, P=0.704) or a favourable outcome between patients treated with DT and BT (35.1% versus 33.3%, P=0.846). Patients treated with DT had a lower intracranial haemorrhage (ICH) rate (40.4% versus 59.3%, P=0.046), but the difference was not significant for symptomatic ICH (sICH, 12.3% versus 16.7%, P=0.511) or asymptomatic ICH (aICH, 28.1% versus 42.6%, P=0.109). After adjusting for potential confounding factors, the ratio of favorable prognosis, successful reperfusion, sICH and mortality did not differ between the two groups. However, there was a higher rate of ICH (OR=2.492, 95% CI 1.005 to 6.180, p=0.049) in the BT group as compared with the DT group. CONCLUSIONS: DT seems equivalent to BT in treating stroke due to carotid T occlusion in favorable outcome, successful recanalization, 90-day morality and sICH. However, BT may increase the incidence of ICH in this specific type stroke.

Leukoaraiosis and earlier neurological outcome after mechanical thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis (LA) severity is associated with earlier neurological outcome in acute stroke patients undergoing mechanical thrombectomy. MATERIALS AND METHODS: In this retrospective multicenter study, we evaluated 273 acute stroke patients treated with mechanical thrombectomy. LA severity was graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of early neurological improvement and early neurological deterioration. Early neurological improvement was defined as a decrease of≥4 points on the NIHSS, or an NIHSS score of zero 24hours after baseline assessment. Early neurological deterioration was defined as an increase of≥4 points on the NIHSS 24hours after baseline assessment. RESULTS: There was a significantly lower early neurological improvement rate (17.1% versus 39.2%; P=0.006) and non-significantly higher early neurological deterioration rate (29.3% versus 17.7%; P=0.084) in patients with severe LA (sLA) compared with patients with absent-to-moderate LA. In multivariable analysis, sLA was inversely associated with early neurological improvement (OR, 0.31; 95% CI, 0.13-0.78; P=0.012). There was no significant association of sLA with early neurological deterioration. However, in patients without symptomatic intracranial hemorrhage, sLA was an independent predictor of early neurological deterioration (OR, 2.65; 95% CI, 1.09-6.45; P=0.032). CONCLUSIONS: sLA is a significant negative predictor of early neurological improvement and is an independent predictor of early neurological deterioration in patients without symptomatic intracranial hemorrhage.

Safety of Intra-Arterial Tirofiban Administration in Ischemic Stroke Patients after Unsuccessful Mechanical Thrombectomy.

PURPOSE: To assess the safety of low-dose intra-arterial (IA) tirofiban bolus after unsuccessful mechanical thrombectomy in patients with ischemic stroke due to large artery occlusion in anterior cerebral circulation. MATERIALS AND METHODS: Patients with ischemic stroke who were treated with mechanical thrombectomy were enrolled in a multicenter registry. Low-dose tirofiban was injected into the residual arterial thrombus in patients after unsuccessful mechanical thrombectomy. The major safety measurement was defined as symptomatic intracranial hemorrhage (SICH). The functional outcome at 90 days was assessed with the modified Rankin Scale, and a score of 0-2 was defined as favorable. RESULTS: Of the 632 enrolled patients, 154 (24.4%) received IA tirofiban treatment. The SICH rate was 13.6% (21/154) in patients with tirofiban and 16.7% (80/478) in patients without tirofiban (P = .361). IA tirofiban was not associated with increased risk of SICH (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.36-1.31; P = .26). IA tirofiban treatment did not increase the risk of mortality at 90 days of the index stroke (OR, 0.66; 95% CI, 0.36-1.31; P = .15). Patients with large artery atherosclerosis stroke who were treated with tirofiban were associated with decreased risk of death (OR, 11.3% vs 23.4%; P = .042) compared to patients who were not treated with tirofiban. CONCLUSIONS: Low-dose IA tirofiban administration may be relatively safe in patients with ischemic stroke after unsuccessful recanalization.

Efficacy and safety of endovascular thrombectomy in mild ischemic stroke: results from a retrospective study and meta-analysis of previous trials.

BACKGROUND: Mechanical thrombectomy has been proven as a standard care for moderate to severe ischemic stroke with anterior large vessel occlusion (LVO); however, whether it is equally effective in mild ischemic stroke (MIS) is controversial. METHODS: In this retrospective study, a total of 177 Chinese patients presenting with MIS (NIHSS ≤8) and LVO between January 2014 and September 2017 from seven comprehensive stroke centers were identified. Odds of good outcome with endovascular thrombectomy versus medical treatment were obtained by logistic regression analysis and propensity-score matching method, and a meta-analysis pooled results from six studies (n = 733). RESULTS: Good outcome (mRS: 0-1) was 58.2% (46/79) in the thrombectomy and 46.9% (46/98) in the medical group, which showed no statistical significance before adjustment (P = 0.13; OR = 1.57, 95% CI: 0.86 to 2.86). The adjusted ORs of thrombectomy versus medical group were 3.23 (95% CI, 1.35 to 7.73; P = 0.008) by multivariable logistic analysis, 2.78 (1.12 to 6.89; P = 0.02) by propensity score matching analysis, and 3.20 (1.22 to 8.37; P = 0.01) by propensity score matching analysis with additional adjustments, respectively. Thrombectomy treatment did not result in excessive mortality or symptomatic intracranial hemorrhage after adjustments. The meta-analysis did not confirm the associations between good outcome and endovascular treatment. CONCLUSIONS: The current study indicates that endovascular thrombectomy is associated with good functional outcome in MIS patients with LVO, and without additional risk of symptomatic intracranial hemorrhage and mortality. Although the meta-analysis failed to demonstrate its superiority compared to medical treatment, randomized clinical trials are needed.

A GWAS-supported variant interacting with diabetes predicts risk of atherothrombotic stroke in Han Chinese population.

BACKGROUND: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. METHODS: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool. RESULTS: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR = 0.76, 95% CI = 0.58-0.99 and OR = 0.76, 95% CI = 0.58-0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR = 0.63, 95% CI = 0.45-0.88), no hypertension (OR = 0.66, 95% CI = 0.46-0.94), diabetes (OR = 0.33, 95% CI = 0.17-0.64), and smoking (OR = 0.65, 95% CI = 0.44-0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR = 4.48; 95% CI = 2.98-6.72) increased risk of AS. CONCLUSION: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population.

Feasibility of Thrombectomy in Treating Acute Ischemic Stroke Because of Cervical Artery Dissection.

Background and Purpose- Acute ischemic stroke caused by cervical artery dissection tend to result in unfavorable outcomes even with appropriate medical treatment. This study evaluated the safety and effectiveness of endovascular thrombectomy in treating acute ischemic stroke associated with cervical artery dissection. Methods- Patients with acute ischemic stroke and with large artery occlusion associated with dissection were selected. Propensity score matching was performed to increase the comparability. Patients with a 90-day modified Rankin Scale score of 0 to 2 were defined as with favorable outcome. Results- Eighty patients with and 80 patients without thrombectomy were enrolled. After propensity score matching, 48 patients with and 48 patients without thrombectomy were matched for further analysis. Proportion of favorable outcome (modified Rankin Scale score of 0-2) was higher in patients with thrombectomy than in those without (66.7% versus 39.6%; P=0.008). There were no significance differences about the incidence of symptomatic intracranial hemorrhage (8.3% versus 4.2%; P=0.677) and the 90-day mortality (10.4% versus 6.3%; P=0.714) between matched patients with and without thrombectomy. Conclusions- Endovascular thrombectomy seems to be an effective treatment in selected patients with acute ischemic stroke associated with cervical artery dissection, but the safety of thrombectomy needs further research.

A Study of GWAS-Supported Variants of rs9943582 in a Chinese Han Population with Ischemic Stroke: No Associations with Disease Onset and Clinical Outcomes.

BACKGROUND: The variant rs9943582 of APLNR (apelin receptor) was identified by a large-scale study to be associated with an increased risk of ischemic stroke in a Japanese population. We conducted this study to investigate the association between the variant and age of onset and clinical outcomes of ischemic stroke in a Chinese population. METHODS: Improved multiple ligase detection reaction was used to genotype the variant. We compared the mean age at ischemic stroke onset with one-way ANOVA. The Kaplan-Meier method, log-rank test, and Cox proportional hazards regression models were performed to analyze the association between the variant and clinical outcomes (recurrence and death). RESULTS: A total of 916 ischemic stroke patients were recruited for the study. For age at ischemic stroke onset, no significant association was identified with the variant in any genetic model. In addition, the variant was not strongly associated with recurrence and death risk of ischemic stroke, as shown by the results. CONCLUSIONS: The findings indicated that the variant rs9943582 was not associated with age at onset and clinical outcomes of ischemic stroke. However, evidence from well-designed studies with larger and in different ethnic populations are warranted to further explore the effects of APLNR on the ischemic stroke onset and clinical outcomes.

Yellow-emitting carbon dots as fluorescent sensors for the rapid determination of curcumin.

The non-standard use of curcumin could cause some adverse drug reactions, such as diarrhea, nausea and skin allergies. Thus, the curcumin determination was fundamental to disease treatment and prevention. Herein, a facile and efficient fluorescent probe was developed based on carbon dots, which was prepared through hydrothermal method (o-phenylenediamine and N-isopropylacrylamide as the reaction raw materials). Characteristics of the as-fabricated carbon dots (NCDs) were studied through some analysis techniques, such as UV-vis absorption spectroscopy, transmission electron microscopy, Fourier transform infrared instrument, X-ray photoelectron spectroscopy and fluorescence spectrophotometer. Fluorescence quenching phenomenon could be observed after addition of curcumin. This as-prepared fluorescent probe displayed a significant response for the determination of curcumin with a satisfactorily lower detection limit of 0.017 µM and a considerable linear range of 0.5-50 µM compared to reported literatures. Because of the preeminent repeatability and anti-jamming capability, the as-developed CDs suggested mighty potentiality for actual applications of curcumin detection in real samples and temperature sensing.

Effect of Intravenous Tirofiban Versus Placebo on First-Pass Successful Reperfusion in Endovascular Stroke Thrombectomy: Insights From the RESCUE BT Randomized Clinical Trial.

BACKGROUND: First-pass successful reperfusion (FPSR), defined as a successful/complete reperfusion achieved after a single thrombectomy pass, is predictive of favorable outcome in patients with acute ischemic stroke with large-vessel occlusion. It is unknown whether intravenous tirofiban is effective in increasing the rate of FPSR in acute anterior large-vessel occlusion stroke. METHODS AND RESULTS: Patients who had acute large-vessel occlusion stroke presenting within 24 hours and underwent endovascular thrombectomy were analyzed from the RESCUE BT (Intravenous Tirofiban for Patients With Large Vessel Occlusion Stroke) clinical trial, of which the main analysis was neutral. The RESCUE BT trial randomized patients to receive either intravenous tirofiban or placebo before endovascular thrombectomy. The primary end point was FPSR, defined as successful reperfusion (extended thrombolysis in cerebral infarction scale 2b50, 2c, or 3) at first thrombectomy attempt. A modified Poisson regression analysis assessed the association between intravenous tirofiban treatment and FPSR. Of 948 enrolled patients, 463 patients were randomized to the tirofiban group and 485 to the placebo group. The mean age was 67 years, and 41.0% of the patients were women. FPSR was achieved more often in the tirofiban group (30.5% versus 23.5%; adjusted risk ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04). FPSR was associated with a favorable shift to lower modified Rankin Scale disability levels at 90 days (common odds ratio, 1.42 [95% CI, 1.08-1.86]; P=0.01). CONCLUSIONS: In this post hoc analysis of the RESCUE BT trial, treatment with intravenous tirofiban before endovascular thrombectomy was associated with increased FPSR in patients with acute ischemic stroke due to large-vessel occlusion in the anterior circulation. FPSR was associated with reduced 90-day levels of disability. REGISTRATION: URL: http://chictr.org; Unique Identifier: ChiCTR-INR-17014167.

A ratiometric fluorescent probe based on spiropyran in situ switching for tracking dynamic changes of lysosomal autophagy and anticounterfeiting.

Autophagy is the controlled breakdown of cellular components that dysfunctional or nonessential, and the decomposition products are further recycled and synthesized for the normal physiological activities of cells. Lysosomal autophagy has been implicated in cancer, neurological disorders, Parkinson's disease, etc. Therefore, it is necessary to develop a fluorescent probe that can clearly describe the process of lysosomal autophagy. However, there are currently limited fluorescent probes for ratiometric monitoring of the autophagic process in dual channels. To solve this problem, a fluorescent probe based on spiropyran with lysosomal targeting and pH response for ratiometric monitoring the autophagy process of lysosomes were designed. The sensitive response of the probe to pH in vitro was verified by UV and fluorescence spectrum tests. Meanwhile, the probe demonstrated the ability to monitor the intracellular pH fluctuations. In addition, the application of Lyso-SD in the field of anti-counterfeiting has been proposed based on the obvious photoluminescence ability of Lyso-SD under UV irradiation.

The impact of COVID-19 pandemic on treatment delay and short-term neurological functional prognosis for acute ischemic stroke during the lockdown period.

Background: Preventive strategies implemented during the COVID-19 pandemic may negatively influence the management of patients with acute ischemic stroke (AIS). Nowadays, studies have demonstrated that the pandemic has led to a delay in treatment among patients with AIS. Whether this delay contributes to meaningful short-term outcome differences warranted further exploration. Objective: The objective of this study was to evaluate the impacts of the COVID-19 pandemic on treatment delay and short-term outcomes of patients with AIS treated with IVT and MT. Methods: Patients admitted before (from 11/1/2019 to 1/31/2020) and during the COVID-19 pandemic (from 2/1/2020 to 3/31/2020) were screened for collecting sociodemographic data, medical history information, and symptom onset status, and comparing the effect of treatment delay. The patients treated with IVT or MT were compared for delay time and neurological outcomes. Multivariable logistic regression was used to estimate the effect of treatment delay on short-term neurological prognosis. Results: In this study, 358 patients receiving IVT were included. DTN time increased from 50 min (IQR 40-75) before to 65 min (IQR 48-84), p = 0.048. 266 patients receiving MT were included. The DTP was 120 (112-148) min vs. 160 (125-199) min before and during the pandemic, p = 0.002. Patients with stroke during the pandemic had delays in treatment due to the need for additional PPE (p < 0.001), COVID-19 screening processes (p < 0.001), multidisciplinary consultation (p < 0.001), and chest CT scans (p < 0.001). Compared with pre-COVID-19, during the pandemic, patients had a higher likelihood of spontaneous intracranial hemorrhage after IVT (OR: 1.10; 95% CI, 1.03-1.30) and a lower likelihood of mRS scores 0-2 at discharge (OR: 0.90; 95% CI, 0.78-0.99). In logistic regression analysis, high NIHSS score at admission, increasing age, worse pre-admission mRS, large vessel occlusion, admission during the lockdown period, and low mTICI grade after MT were associated with an mRS ≥ 3. Conclusion: The COVID-19 pandemic has had remarkable impacts on the management of AIS. The pandemic might exacerbate certain time delays and play a significant role in early adverse outcomes in patients with AIS.

Higher tea consumption is associated with decreased risk of small vessel stroke.

BACKGROUND & AIM: Observational studies have reported that tea consumption is associated with risk of stroke. However, this observed association is inconsistent, and whether this observed association is due to confounding factors or reverse causation remains unclear. Thus, we applied a two-sample mendelian randomization (MR) approach to determine whether genetically predicted tea consumption is causally associated with risk of stroke, ischemic stroke (IS), and IS subtypes. METHODS: UK Biobank available data (349,376 samples of European ancestry) was used to identify single nucleotide polymorphisms associated with tea consumption (cups/day). The summary statistics for stroke, IS, and IS subtypes were obtained from the MEGASTROKE consortium with 40,585 stroke cases and 406,111 controls. RESULTS: We found that genetically predicted an extra daily cup of tea consumption was casually associated with a reduced risk of small vessel stroke (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69-0.91; P = 0.001), but not with cardioembolic stroke (OR, 0.97; 95% CI, 0.86-1.09; P = 0.582), large artery stroke (OR, 0.95; 95% CI, 0.82-1.10; P = 0.506), stroke (OR, 1.00; 95% CI, 0.95-1.06; P = 0.889) or IS (OR, 0.95; 95% CI, 0.89-1.01; P = 0.083). CONCLUSIONS: Our study provided evidence that genetically predicted an extra daily cup of tea consumption is causally associated with a reduced risk of small vessel stroke.

DEVT: A randomized, controlled, multicenter trial of direct endovascular treatment versus standard bridging therapy for acute stroke patients with large vessel occlusion in the anterior circulation - Protocol.

BACKGROUND: Eight randomized controlled trials have consistently shown that endovascular treatment plus best medical treatment improves outcome after acute anterior proximal intracranial large vessel occlusion strokes. Whether intravenous thrombolysis prior to endovascular treatment in patients with anterior circulation, large vessel occlusion is of any additional benefits remains unclear. OBJECTIVE: This study compares the safety and efficacy of direct endovascular treatment versus intravenous recombinant tissue-type plasminogen activator bridging with endovascular treatment (bridging therapy) in acute stroke patients with intracranial internal carotid artery or middle cerebral artery-M1 occlusion within 4.5 h of symptom onset. METHODS AND DESIGN: The DEVT study is a randomized, controlled, multicenter trial with blinded outcome assessment. This trial uses a five-look group-sequential non-inferiority design. Up to 194 patients in each interim analysis will be consecutively randomized to direct endovascular treatment or bridging therapy group in 1:1 ratio over three years from about 30 hospitals in China. OUTCOMES: The primary end-point is the proportion of independent neurological function defined as modified Rankin scale score of 0 to 2 at 90 days. The primary safety measure is symptomatic intracerebral hemorrhage at 48 h and mortality at 90 days. TRIAL REGISTRY NUMBER: ChiCTR-IOR-17013568 (www.chictr.org.cn).

Assessment of Endovascular Treatment for Acute Basilar Artery Occlusion via a Nationwide Prospective Registry.

Importance: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. Objective: To evaluate the association between EVT and clinical outcomes of patients with acute BAO. Design, Setting, and Participants: This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. Main Outcomes and Measures: The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality. Results: A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55]; P < .001). Moreover, EVT was associated with a significantly higher rate of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P < .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P < .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P < .001). Conclusions and Relevance: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.

Interleukin-17 receptor C gene polymorphism reduces treatment effect and promotes poor prognosis of ischemic stroke.

OBJECTIVE: To study the relationship between Interleukin-17 receptor C (IL-17RC) gene polymorphism and ischemic stroke (IS). METHODS: Three hundred cases of IS patients and 300 cases of the healthy controls were selected. Serum of IS patients and the controls was collected. The relative mRNA levels of IL-17, IL-17RC, IL-6, IL-8, G-CSF and granulocyte-macrophage colony stimulating factor (GM-CSF) by qRT-PCR. The protein expression of IL-17 and IL-17RC was determined by Western blotting. IL-17RC genotype was identified by PCR amplification. The proportion of IL-17RC, SNP and re37511 in IS and control group was determined. The treatment effect on IS and prognosis of patients with IL-17RC, SNP and re37511 was compared. RESULTS: The relative mRNA levels of IL-17, IL-17RC, IL-6, IL-8, G-CSF and GM-CSF in IS group were significantly higher than the control group. The protein expression of IL-17 and IL-17RC in IS group was also markedly higher than the control group. The proportion of IL-17RC re37511 in IS group was much larger than control group and proportion of IL-17RC much less. The percent of poor treatment effect in re37511 was much larger than IL-17RC. The percent of death and recrudescence in patients with IL-17RC re37511 was the highest. CONCLUSION: IS up-regulates the expression of IL-17 and IL-17RC. IL-17RC re37511 indicates the patients have a poorer treatment effect and prognosis.

Leukoaraiosis severity and outcomes after mechanical thrombectomy with stent-retriever devices in acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis severity is associated with outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices. METHODS: In this retrospective multicenter study, we evaluated 251 acute stroke patients (pretreatment National Institutes of Health Stroke Scale score ≥8) treated with stent-retriever devices. Leukoaraiosis severity was graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of good functional outcome, defined as a modified Rankin Scale of 0-2 at 90 days. RESULTS: Significantly fewer patients in the severe LA group than in the absent-to-moderate LA group achieved a good functional outcome (18.4% vs 50.2%, P<0.001). In multivariable analysis, severe leukoaraiosis was a significant negative predictor of good functional outcome at 90 days (OR, 0.27; 95% CI 0.10-0.77; P=0.014). CONCLUSIONS: The severity of leukoaraiosis is independently associated with 90-day functional outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices.

Neutrophil to Lymphocyte Ratio as a Predictor of Restenosis After Angioplasty and Stenting for Asymptomatic Carotid Stenosis.

The inflammatory response plays a vital role in the development of in-stent restenosis (ISR) after carotid angioplasty and stenting (CAS). The neutrophil to lymphocyte ratio (NLR) has been suggested as a sensitive inflammatory marker. We explored the association between NLR and ISR in CAS patients. A total of 427 patients who underwent CAS were enrolled. Neutrophil to lymphocyte ratio was measured before the procedure. Clinical examination and radiographic evaluation were performed at 6 months and annually after the procedure. In-stent restenosis was defined as ≥50% stenosis in the treated lesion. Cox regression was used to identify predictors of ISR after CAS. Of the 459 arteries (in 427 patients) with CAS, 72 (15.7%) were identified with ISR during a mean follow-up of 14.6 (19.1) months (range, 0.7-120.7 months). Increased NLR (≥2.13) was significantly related to ISR in patients with asymptomatic stenosis ( P = .001). However, significance was not observed in symptomatic stenosis. On multivariate analysis, baseline NLR ≥ 2.13 (hazard ratio [HR], 2.74; 95% confidence interval [CI], 1.46-5.14), smoking (HR, 1.99; 95% CI, 1.11-3.58), residual stenosis (HR, 1.12; 95% CI, 1.09-1.15), and baseline glucose level (HR, 1.01; 95% CI, 1.01-1.02) were associated with ISR. Elevated NLR may be a predictor of ISR after CAS for asymptomatic stenosis.

Enhancing the effects of transcranial magnetic stimulation with intravenously injected magnetic nanoparticles.

Transcranial magnetic stimulation (TMS) is a non-invasive and clinically approved method for treating neurological disorders. However, the relatively weak intracranial electric current induced by TMS is an obvious inferiority which can only produce limited treatment effects in clinical application. The present study aimed to investigate the possibility of enhancing the effects of TMS with intravenously administrated magnetic nanoparticles. To facilitate crossing of the blood-brain barrier (BBB), the superparamagnetic iron oxide nanoparticles (SPIONs) were coated with carboxylated chitosan and poly(ethylene glycol). To aid the nanoparticles in crossing the BBB and targeting the predesigned brain regions, an external permanent magnet was attached to the foreheads of the rats before the intravenous administration of SPIONs. The electrophysiological tests showed that the maximum MEP amplitude recorded in an individual rat was significantly higher in the SPIONs + magnet group than in the saline group (5.78 ± 2.54 vs. 1.80 ± 1.55 mV, P = 0.015). In the M1 region, biochemical tests detected that the number density of c-fos positive cells in the SPIONs + magnet group was 3.44 fold that of the saline group. These results suggest that intravenously injected SPIONs can enhance the effects of TMS in treating neurological disorders.