Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy.

BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment within 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered within 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events: a prospective observational study.

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations. However, the ability of retinal vasculature changes, specifically focusing on retinal vessel diameter, to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively. While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events, they have not incorporated this information into a predictive model. Therefore, this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke. Additionally, we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors. We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University. All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years. We found that, after adjusting for related risk factors, patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin (MAD0.5-1.0DD) of ≥ 74.14 µm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin (MVD0.5-1.0DD) of ≥ 83.91 µm tended to experience recurrent cerebrovascular events. We established three multivariate Cox proportional hazard regression models: model 1 included traditional risk factors, model 2 added MAD0.5-1.0DD to model 1, and model 3 added MVD0.5-1.0DD to model 1. Model 3 had the greatest potential to predict subsequent cerebrovascular events, followed by model 2, and finally model 1. These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke, and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.

FUS-mediated HypEVs: Neuroprotective effects against ischemic stroke.

Few studies have investigated the properties and protein composition of small extracellular vesicles (sEVs) derived from neurons under hypoxic conditions. Presently, the extent of the involvement of these plentiful sEVs in the onset and progression of ischemic stroke remains an unresolved question. Our study systematically identified the characteristics of sEVs derived from neurons under hypoxic conditions (HypEVs) by physical characterization, sEV absorption, proteomics and transcriptomics analysis. The effects of HypEVs on neurites, cell survival, and neuron structure were assessed in vitro and in vivo by neural complexity tests, magnetic resonance imaging (MRI), Golgi staining, and Western blotting of synaptic plasticity-related proteins and apoptotic proteins. Knockdown of Fused in Sarcoma (FUS) small interfering RNA (siRNA) was used to validate FUS-mediated HypEV neuroprotection and mitochondrial mRNA release. Hypoxia promoted the secretion of sEVs, and HypEVs were more easily taken up and utilized by recipient cells. The MRI results illustrated that the cerebral infarction volume was reduced by 45% with the application of HypEVs, in comparison to the non- HypEV treatment group. Mechanistically, the FUS protein is necessary for the uptake and neuroprotection of HypEVs against ischemic stroke as well as carrying a large amount of mitochondrial mRNA in HypEVs. However, FUS knockdown attenuated the neuroprotective rescue capabilities of HypEVs. Our comprehensive dataset clearly illustrates that FUS-mediated HypEVs deliver exceptional neuroprotective effects against ischemic stroke, primarily through the maintenance of neurite integrity and the reduction of mitochondria-associated apoptosis.

N-acetyl-L-leucine protects MPTP-treated Parkinson's disease mouse models by suppressing Desulfobacterota via the gut-brain axis.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have not yet been elucidated. Our study aimed to investigate the correlation between gut microbiota disturbances and feces metabolic disorders in PD. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models and observed mice's motor symptoms, dopaminergic (DA) neuron death, and gastrointestinal dysfunction. To identify alterations in microbiota and metabolome, feces were collected from mice and analyzed using 16 S ribosomal RNA sequencing feces metabolomics. Pearson analysis was utilized to investigate correlations between the abundances of gut microbiota components and the levels of gut microbiota metabolites, displaying their interaction networks. Our findings revealed a significant increase in Desulfobacterota in the PD mouse model and 151 differentially expressed fecal metabolites between PD and vehicle mice. Moreover, Pearson correlation analysis suggested that the protective factor N-acetyl-L-leucine (NALL) may be associated with neuroinflammation in the striatum and substantia nigra, which also had a negative relationship with the concentration of Desulfobacterota. Additionally, we found that oral administration of NALL alleviated MPTP-induced Motor Impairments and DA neuronal deficits. All in all, we concluded that the decrease of NALL might lead to a significant increase of Desulfobacterota in the MPTP model mouse and subsequently result in the damage of DA neurons via the gut-brain aix pathway.

Case report: Intensive statin and PCSK-9 inhibitor combo reduces plaque volume and stenosis in ischemic stroke patient.

Intracranial atherosclerotic ischemic stroke dramatically impacts the quality of life among the elderly. Statins therapy has been proven to be effective in plaque stabilization and alleviation in patients with intracranial atherosclerotic ischemic stroke. According to recent studies, these effects may be directly related to lipid levels rather than specific lipid-lowering drugs. Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK-9 inhibitor) are newer effective lipid-lowering drugs increasingly prescribed to patients at high cardiovascular risk to lower LDL cholesterol. Studies have provided evidence that PCSK9 inhibitor combined with statin therapy can lead to a decrease in the plaque volume measured by intravascular ultrasound in coronary heart disease patients. But the efficacy of combination of the two drugs in symptomatic intracranial artery stenosis has been unknown. Here we provide a case which was reported to suggest that a combination of Evolocumab and intensive statin therapy might reverse or alleviate symptomatic intracranial artery stenosis.

Thrombus migration in patients with acute ischaemic stroke undergoing endovascular thrombectomy.

OBJECTIVE: The impact of thrombus migration (TM) prior to endovascular thrombectomy (EVT) on clinical outcomes and revascularisation rates remains unknown. We aimed to examine whether preinterventional TM modifies the treatment effects of direct EVT versus bridging EVT in acute large vessel occlusion patients. METHODS: All patients undergoing catheter angiography in the Direct Intra-arterial thrombectomy in order to Revascularise acute ischaemic stroke patients with large vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicentre randomised clinical Trial were included. TM was determined by radiologists unaware of the study by analysing discrepancies between computed tomographic angiography at baseline and first-run digital subtraction angiography before EVT. The primary outcome was the score on the modified Rankin scale (mRS) assessed at 90 days. RESULTS: Of 627 included patients, the TM rate was 11.3% (71/627). In the multivariable logistic regression model, baseline National Institutes of Health Stroke Scale score (adjusted OR 0.956, 95% CI 0.916 to 0.999; p=0.043) and intravenous thrombolysis (adjusted OR 2.614, 95% CI 1.514 to 4.514; p<0.001) were independently associated with TM. The patients with TM were less likely to be completely recanalised than those without TM (21.27% vs 36.23%, p=0.040). The interaction of TM and the EVT treatment effect did not significantly affect mRS shift analysis (p=0.687) or mRS scores of 0 to 1 (p=0.436). CONCLUSION: Preinterventional TM does not modify the treatment effects of direct versus bridging EVT on functional outcomes in patients with acute ischaemic stroke with anterior large vessel occlusion. TM leads to a lower complete recanalisation rate.

Comparison of Computed Tomography Perfusion and Multiphase Computed Tomography Angiogram in Predicting Clinical Outcomes in Endovascular Thrombectomy.

BACKGROUND: In patients with acute stroke who undergo endovascular thrombectomy, the relative prognostic power of computed tomography perfusion (CTP) parameters compared with multiphase CT angiogram (mCTA) is unknown. We aimed to compare the predictive accuracy of mCTA and CTP parameters on clinical outcomes. METHODS: We included patients with acute ischemic stroke who had anterior circulation large vessel occlusion within 24 hours of onset in Melbourne Brain Centre at the Royal Melbourne Hospital. All patients underwent CTP for endovascular thrombectomy, and the mCTA collateral score was determined using CTP-reconstructed mCTA images. The primary outcome was 90-day functional outcomes defined by modified Rankin Scale. Multivariable logistic regression models analyzed associations between mCTA and CTP parameters and 90-day functional outcomes. The ability to discriminate 90 days-functional outcomes was compared between mCTA collateral score and CTP parameters using receiver operating curve analysis and C statistics. RESULTS: One hundred and twenty patients were included. The median age was 69 years (interquartile range, 60-79), the median baseline National Institutes of Health Stroke Scale score was 14 (interquartile range, 9-19). The baseline ischemic core volume, defined by CTP-based relative cerebral blood flow <30%, was associated with excellent functional outcome (modified Rankin Scale score 0-1; odds ratio, 0.942 [-0.897 to -0.989]; P=0.015) and poor functional outcome (modified Rankin Scale score 5-6; odds ratio, 1.032 [1.007-1.056]; P=0.010) at 90 days in the analysis of multivariable regression. There was no significant association between the mCTA score and excellent functional outcome (P=0.58) or poor functional outcome (P=0.155). The relative cerebral blood flow <30%-based regression model best fit the data for the 90-day poor functional outcome (C statistic, 0.834). CONCLUSIONS: The CTP-based ischemic core volume may provide better discrimination for 90-day functional outcomes for patients with acute stroke undergoing endovascular thrombectomy than the mCTA collateral score.

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking. We aim to investigate whether the CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage. METHODS: CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra volumes. CircOGDH interacted with miR-5112 (microRNA-5112) in primary cortical neurons was detected by fluorescence in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. Adenovirus-mediated CircOGDH knockdown ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type IV, alpha IV) overexpression. Transmission electron microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes. RESULTS: CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls. Partial regression analysis revealed that CircOGDH expression was positively correlated with the size of penumbra in patients with AIS. Sequestering of miR-5112 by CircOGDH enhanced COL4A4 expression to elevate neuron damage. Additionally, knockdown of CircOGDH significantly enhanced neuronal cell viability under ischemic conditions. Furthermore, the expression of CircOGDH in brain tissue was closely related to that in the serum of middle cerebral artery occlusion mice. Finally, we found that CircOGDH was highly expressed in plasma exosomes of patients with AIS compared with those in noncerebrovascular disease individuals. CONCLUSIONS: These results demonstrate that CircOGDH is a potential therapeutic target for regulating ischemia neuronal viability, and is enriched in neuron-derived exosomes in the peripheral blood, exhibiting a predictive biomarker of penumbra in patients with AIS.

Corrigendum: Efficacy and Safety of Adherence to dl-3-n-Butylphthalide Treatment in Patients With Non-disabling Minor Stroke and TIA-Analysis From a Nationwide, Multicenter Registry.

[This corrects the article DOI: 10.3389/fneur.2021.720664.].

Efficacy and Safety of Adherence to dl-3-n-Butylphthalide Treatment in Patients With Non-disabling Minor Stroke and TIA-Analysis From a Nationwide, Multicenter Registry.

Background: Dl-3-n-Butylphthalide (NBP) has the potential to improve clinical outcomes in acute ischemic stroke patients by improving collateral circulation. We aimed to evaluate the efficacy and safety of NBP in patients with non-disabling minor ischemic stroke and transient ischemic attack (TIA). Methods: The BRIDGE (the observation study on clinical effectiveness of NBP on patients with non-disabling ischemic cerebrovascular disease) is a prospective registry to monitor the efficacy and safety of NBP therapy in acute non-disabling ischemic stroke or high-risk TIA. Non-disabling minor ischemic stroke patients within 48 h were enrolled across 51 stroke centers in China. We divided patients into NBP compliance or non-compliance groups according to their adherence to NBP. The primary outcome was the favorable functional outcome at 90 days, defined as a modified Rankin scale (mRS) <2. Results: Between 10th October 2016 and 25th June 2019, 3,118 patients were included in this analysis. In multivariable analysis, Between 10th October 2016 and 25th June 2019, 3,118 patients were included in this analysis. In multivariable analysis, after adjusting for common risk factors and demographic factors, NBP-compliance group has a higher proportion of favorable functional outcome (92.1 vs. 87.4%, adjusted odds ratio 2.00, 95% confidence interval, 1.50­2.65), and a higher stroke recurrence rate (2.40 vs. 0.31%, adjusted odds ratio 8.86, 95% confidence interval, 3.37­23.30) than the NBP-non-compliance group. There was no significant difference in death and intracranial hemorrhage rate between the two groups. In subgroup analysis, patients with National Institutes of Health Stroke Scale (NIHSS) scores from 3 to 5 who complied to NBP therapy had a higher rate of favorable functional outcomes than the NBP-non-compliance group. [88.82 vs. 76.21%, adjusted odds ratio 2.52 (1.81­3.50), adjusted interaction P = 0.00]. Conclusion: In non-disabling minor ischemic stroke or TIA patients, compliance with NBP therapy led to better 90-day functional outcomes despite a higher risk of recurrence, and this effect seems to be stronger in patients with NIHSS scores of 3-5. Further large randomized, double-blind controlled studies to analyse the association between NBP and functional outcome is warranted in the coming future.

Optimal Tissue Reperfusion Estimation by Computed Tomography Perfusion Post-Thrombectomy in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b is defined as successful reperfusion. However, mTICI has rarely been correlated with dynamic perfusion imaging postendovascular therapy for acute stroke. We aimed to study the proportion of tissue optimal reperfusion (TOR) postendovascular therapy across different grades of mTICI. METHODS: We conducted a single-center retrospective analysis of patients with acute ischemic strokes who had endovascular therapy between 2018 and 2019. Computer tomography perfusion or magnetic resonance perfusion was performed before and after endovascular therapy. Tmax+6 volume reduction of >90% was defined as TOR. Comparisons of proportions of TOR in different grades of mTICI were performed. In the present study, the requirement for informed consents was waived. RESULTS: Eighty-two patients were included. The difference in the proportion of TOR for TICI categories was statistically significant (mTICI score 0, 0%, mTICI score 2A, 0%, mTICI score 2b, 50.0%, mTICI score 2c, 80.0%, mTICI score 3, 81.3%, χ2=14.035, P=0.003). Multivariable logistic regression showed that lower age (odds ratio, 0.932, P=0.017), onset-to-tissue-type plasminogen activator time (odds ratio, 0.980, P=0.005) and TOR (odds ratio, 8.764, P=0.031) were associated with favorable functional outcome. CONCLUSIONS: The proportion of TOR achieved by mTICI score of 2b was significantly lower than mTICI score of 2c and mTICI score of 3. TOR was associated with favorable functional outcome, and the degree of reperfusion was more strongly correlated with outcomes than the mTICI scores.

Comparative Study of Multi-Delay Pseudo-Continuous Arterial Spin Labeling Perfusion MRI and CT Perfusion in Ischemic Stroke Disease.

With the aging population, stroke has gradually become the leading cause of death and disability among adults. It is necessary to verify whether multi-delay pseudo-continuous arterial spin labeling (pCASL) MRI can be used as a standard neuroimaging protocol in the patients with ischemic stroke. We aimed to investigate the clinical utility of multi-delay pCASL for evaluating cerebral perfusion in ischemic stroke disease. Twenty-one ischemic stroke patients [18 men and 3 women; median age, 62 years (age range, 37-84 years)] were enrolled in this study. All patients underwent examinations, including the multi-delay pCASL protocol (using 6 PLDs between 1,000 and 3,500 ms) and computed tomography perfusion (CTP). The cerebral blood flow (CBF) and arterial transit time (ATT) maps were obtained by the multi-delay pCASL protocol, while CBF and mean transit time (MTT) maps were derived by CTP measurements. Based on the voxel level analysis, Pearson correlation coefficients were used to estimate the associations between the two modalities in the gray matter, white matter, and whole brain of each subject. Moderate to high positive associations between ASL-CBF and CTP-CBF were acquired by voxel-level-wise analysis in the gray matter, white matter, and whole brain of the enrolled patients (all P < 0.005), and the average Pearson correlation coefficients were 0.647, 0.585, and 0.646, respectively. Highly significant positive correlations between ASL-ATT and CTP-MTT were obtained by voxel-level-wise associations in the gray matter, white matter, and whole brain (all P < 0.005), and the average Pearson correlation coefficients were 0.787, 0.707, and 0.799, respectively. In addition, significant associations between ASL and CT perfusion were obtained in the gray, white matter and whole brain, according to the subgroup analyses of patient's age and disease stage. There is a correlation between perfusion parameters from multi-delay pCASL and CT perfusion imaging in patients with ischemic stroke. Multi-delay pCASL is radiation-free and non-invasive, and could be an alternative method to CT scans for assessing perfusion in ischemic stroke disease.

Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update on organizational stroke management

Stroke is characterised by high morbidity, mortality and disability, which seriously affects the health and safety of the people. Stroke has become a serious public health problem in China. Organisational stroke management can significantly reduce the mortality and disability rates of patients with stroke. We provide this evidence-based guideline to present current and comprehensive recommendations for organisational stroke management. A formal literature search of MEDLINE (1 January 1997 through 30 September 2019) was performed. Data were synthesised with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The Chinese Stroke Association's Levels of Evidence grading algorithm was used to grade each recommendation. Evidence-based guidelines are presented for the organisational management of patients presenting with stroke. The focus of the guideline was subdivided into prehospital first aid system of stroke, rapid diagnosis and treatment of emergency in stroke centre, organisational management of stroke unit and stroke clinic, construction of regional collaborative network among stroke centres and evaluation and continuous improvement of stroke medical quality. The guidelines offer an organisational stroke management model for patients with stroke which might help dramatically.

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update on organizational stroke management.

AIM: Stroke is characterised by high morbidity, mortality and disability, which seriously affects the health and safety of the people. Stroke has become a serious public health problem in China. Organisational stroke management can significantly reduce the mortality and disability rates of patients with stroke. We provide this evidence-based guideline to present current and comprehensive recommendations for organisational stroke management. METHODS: A formal literature search of MEDLINE (1 January 1997 through 30 September 2019) was performed. Data were synthesised with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The Chinese Stroke Association's Levels of Evidence grading algorithm was used to grade each recommendation. RESULTS: Evidence-based guidelines are presented for the organisational management of patients presenting with stroke. The focus of the guideline was subdivided into prehospital first aid system of stroke, rapid diagnosis and treatment of emergency in stroke centre, organisational management of stroke unit and stroke clinic, construction of regional collaborative network among stroke centres and evaluation and continuous improvement of stroke medical quality. CONCLUSIONS: The guidelines offer an organisational stroke management model for patients with stroke which might help dramatically.

Retinal Microvascular Changes in Subtypes of Ischemic Stroke.

Aims: Retinal microvasculature shares prominent similarities with the brain vasculature. We aimed to assess the association between retinal microvasculature and subtypes of ischemic stroke. Method: We consecutively enrolled ischemic stroke patients within 7 days of onset, who met the criteria of subtype of atherothrombosis (AT), small artery disease (SAD), or cardioembolism (CE) according to a modified version of the Trial of Org 10172 in Acute Stroke Treatment (NEW-TOAST). Digital fundus photographs were taken within 72 h of hospital admission using a digital camera (Topcon TRC-50DX), and fundus photographs were semi-automatically measured by software (Canvus 14 and NeuroLucida) for retinal vasculature parameters. Results: A total of 141 patients were enrolled, including 72 with AT, 54 with SAD, and 15 with CE. AT subtype patients had the widest mean venular diameter within 0.5-1.0 disk diameter (MVD0.5-1.0DD) followed by SAD and CE subtypes (86.37 ± 13.49 vs. 83.55 ± 11.54 vs. 77.90 ± 8.50, respectively, P = 0.047); CE subtype patients had the highest mean arteriovenous ratio within 0.5-1.0 disk diameter (MAVR0.5-1.0DD) followed by the AT and SAD subtype groups (0.97 ± 0.03 vs. 0.89 ± 0.99 vs. 0.89 ± 0.11, respectively, P = 0.010); SAD subtype patients were found with the highest mean venular tortuosity within 0.0-2.0 disk diameter (MVT0.0-2.0DD) followed by the AT and CE subtypes (1.0294 ± 0.0081 vs. 1.0259 ± 0.0084 vs. 1.0243 ± 0.0066, respectively, P = 0.024). After adjusting for clinic characteristics, MVD0.5-1.0DD was significantly different among AT, SAD, and CE subtypes (P = 0.033). By receiver operating characteristic curve analysis, MVD0.5-1.0DD predicted the AT subtype (area 0.690, 95% confidence interval, 0.566-0.815), with a cutoff value of 82.23 µm (sensitivity 61.1%, specificity 73.3%). Conclusion: Retinal MVD0.5-1.0DD (>82.23 µm) might be associated with the AT stroke subtype; however, we need large-scale prospective studies in future to explore the underlying mechanism and causal explanation for this finding.

Blood pressure variability estimated by ARV is a predictor of poor short-term outcomes in a prospective cohort of minor ischemic stroke.

Prior studies have shown that patients with minor ischemic stroke have substantial disability rates at hospital discharge. We sought to determine whether blood pressure variability (BPV) estimated by average real variability (ARV) is one of the predictors of poor outcome at 90 days. Four hundred fifty-one consecutive patients with ischemic stroke treated within 7 days after onset were enrolled prospectively. Baseline magnetic resonance imaging (MRI) was performed on all subjects. Blood pressure was measured for all recruited patients every 2 hours in the first 24 hours after admission, followed by measurements collected every 4 hours from day 2 to day 7 after admission. ARV was used to estimate BPV. A total of 192 patients with minor ischemic stroke were enrolled, and 11 of them (5.7%) had poor outcomes. Univariate regression analysis showed that early neurological deterioration (X2 = 21.44, P = 0.000), severe symptomatic large artery stenosis or occlusion (X2 = 9.260, P = 0.000), large artery atherosclerotic stroke (X2 = 7.14, P = 0.002), total cholesterol (TC), and D2-7 SBP-ARV (t = 5.449, P = 0.001) of the poor outcome group were significantly higher than those of the good outcome group. Multivariate logistic regression analysis showed that early neurological deterioration (OR 4.369, 95% CI 3.54, 15.65; P = 0.001), severe symptomatic large artery stenosis or occlusion (OR 5.56, 95% CI 3.56, 13.65; P = 0.000), large artery atherosclerotic stroke (OR 3.56, 95% CI 1.45, 7.48; P = 0.004), and D2-7 SBP-ARV (OR 3.96, 95% CI 1.90, 20.18, P = 0.008) were significantly related to poor outcomes. In conclusion, approximately 5.7% of minor ischemic stroke patients had poor outcomes. D2-7 SBP-ARV, early neurologic deterioration, severe symptomatic artery stenosis or occlusion, and large atherosclerotic stroke were the independent risk factors of poor short-term outcomes.

Association of aquaporin­1 with tumor migration, invasion and vasculogenic mimicry in glioblastoma multiforme.

The present study aimed to assess the expression and functional role of aquaporin-1 (AQP1) in glioblastoma multiforme (GBM) migration, invasion and vasculogenic mimicry (VM). In the primary human gliomas and human glioma­derived cell lines tested, it was observed that the expression of AQP1 was upregulated. In addition, it was demonstrated that silencing of AQP1 expression resulted in decreased migration and invasion, in addition to vasculogenic mimicry in vitro. It was additionally observed that silencing of AQP1 expression resulted in in vivo inhibition of tumor growth, a decrease in the expression of invasion­associated protein, and suppression of VM formation. Based on these data, it was concluded that AQP1 may serve a role in GBM migration, invasion and VM formation, and that it may serve as a novel diagnostic/prognostic biomarker and a potential therapeutic target.

Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS-China): results from a prospective double-blind randomised clinical trial.

AIM: The role of clopidogrel in treating patients with acute ischaemic stroke is unclear. We have conducted the clinical trial in order to evaluate the efficacy and safety of clopidogrel with a loading dose in treating patients with non-cardiogenic acute ischaemic stroke. METHOD: Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS-China) was a prospective, randomised, double-blind and placebo-controlled clinical trial in China. Patients with acute ischaemic stroke of non-cardiogenic origin within 48 hours of onset were enrolled and those received thrombolysis were excluded. Enrolled patients were divided into two treatment groups: loading dose and routine dose. The primary outcome was the incidence of stroke recurrence or progression within 7 days. Primary safety outcome was measured by life-threatening haemorrhage. An intent-to-treat analysis was used for the statistical analysis. RESULTS: From March 2008 to March 2010, a total of 303 patients from 16 centres were recruited into this study; six were excluded because of lack of basic information. Since the enrolment was slow and the study drug expired in March 2010, this clinical trial was stopped earlier than planned. No significant baseline and demographic differences were seen between the two groups. There was no difference in primary outcome between the loading dosage group 16.1% (24/149) and control group 14.9% (22/148), respectively (p=0.782). The mortality and disability rate within 90 days in loading dose group (19.6%) was slightly lower than that in controlled group (23.4%), p=0.444. Loading dose group had two (1.3%) cases of fatal haemorrhage and control group had four (2.7%) within 90 days, p=0.674. No significant difference was detected in other adverse events between the groups. CONCLUSION: In our study stopped early due to slow enrolment, loading dose of clopidogrel does not reduce the risk of recurrent stroke. Future trials with sufficient number of patients enrolled are needed to re-examine this hypothesis.