Association between liver fibrosis and stroke recurrence in young patients with ischemic stroke.

BACKGROUND AND AIM: Stroke incidence rates are rising among young adults. Liver fibrosis has recently been recognized as a risk factor for cardiovascular events and stroke in the general population. It remains unclear whether liver fibrosis influences the prognosis of stroke. We aimed to evaluate the association between liver fibrosis and stroke recurrence in young stroke patients. METHODS AND RESULTS: Young adults with first-ever ischemic stroke were enrolled from a prospective stroke registry and were followed up for stroke recurrence. Liver fibrosis was evaluated by Fibrosis-4 (FIB-4) score and was stratified into three categories. Cox regression analysis was performed to assess the relationship between liver fibrosis and stroke recurrence. Over a median follow-up of 3.1 (1.7-4.6) years, 72 (11.6%) recurrent strokes occurred among 621 patients. According to the FIB-4 score, 73 (11.7%) patients had indeterminate fibrosis, while 11 (1.8%) had advanced fibrosis. Univariate Cox analysis revealed that patients with a high FIB-4 score were more likely to experience stroke recurrence than those with a low FIB-4 score (hazard ratio 3.748, 95% confidence interval 1.359-10.332, P = 0.011). After adjusting for potential confounders in the multivariate analysis, FIB-4 score remained an independent risk factor. CONCLUSIONS: Young stroke patients with advanced liver fibrosis were at a greater risk of stroke recurrence. Evaluating liver fibrosis may provide valuable information for stroke risk stratification, and the FIB-4 score could serve as a useful tool.

Intrinsic Wave Velocity Propagation: A Novel Parameter for Assessing the Effect of Anthracycline Chemotherapy Agents on Cardiac Diastolic Function in Breast Cancer Patients.

OBJECTIVE: Anthracycline chemotherapeutic agents have significant cardiotoxicity. The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular (LV) myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation (IVP), and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment. METHODS: A total of 68 newly diagnosed breast cancer patients, who were treated with anthracycline-based chemotherapy, were analyzed. Transthoracic echocardiography was performed at baseline (T0), and after 1, 2, 3, 4 and 8 chemotherapeutic cycles (T1, T2, T3, T4 and T5, respectively). Then, the IVP, LV strain parameters [global longitudinal strain (GLS), longitudinal peak strain rate at systole (LSRs), longitudinal peak strain rate at early diastole (LSRe), longitudinal peak strain rate at late diastole (LSRa), and the E/LSRe ratio], and conventional echocardiographic parameters were obtained and further analyzed. A relative reduction of >15% in GLS was considered a marker of early LV subclinical dysfunction. RESULTS: Compared to the T0 stage, IVP significantly increased at the T1 stage. However, there were no significant changes in GLS, LSRs, or LSRe between the T0 and T1 stages. These parameters significantly decreased from the T2 stage. LSRa started to significantly decrease at the T5 stage, and the E/LSRe ratio started to significantly increase at the T3 stage (all P<0.05). At the T0 stage, IVP (AUC=0.752, P<0.001) had a good predictive value for LV subclinical dysfunction after chemotherapy. CONCLUSIONS: IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.

Exploring the prospect of intrinsic wave propagation in evaluating myocardial stiffness among patients with type 2 diabetes.

Background: Diabetes predisposes affected individuals to impaired myocardial perfusion and ischemia, leading to cardiac dysfunction. Increased myocardial stiffness is an independent and significant risk factor in diastolic dysfunction. This study sought to estimate myocardial stiffness in Type 2 diabetes (T2DM) patients using the intrinsic wave velocity propagation (IVP) along the longitudinal wall motion during late diastole and evaluate the value of IVP in assessing cardiac function and structure. Methods: 87 and 53 participants with and without T2DM (control group) were enrolled. Of the 87 T2DM patients (DM group), 43 were complicated with hypertension (DM + H group), and 44 were not (DM-H group). Ultrasound parameters were measured and analyzed, including color M-mode flow propagation velocity, global longitudinal systolic strain (GLS), and IVP. Results: IVP was higher in the DM group than in the control group (1.62 ± 0.25 m/s and 1.40 ± 0.19 m/s, P < 0.001). After stratification for hypertension, IVP in both DM + H (1.71 ± 0.25 m/s) and DM-H (1.53 ± 0.20 m/s) groups were found to be significantly higher than that in the control group (1.40 ± 0.19 m/s); also, the difference of IVP between DM + H and DM-H group reached statistical significance. Moreover, IVP was significantly correlated with flow propagation velocity during early diastole (Pve) (r = -0.580, P < 0.001), flow propagation velocity during late diastole (Pva) (r = 0.271, P < 0.001), GLS (r = 0.330, P < 0.001), interventricular septal thickness at end-diastole (IVSd) (r = 0.321, P < 0.001), blood glucose (r = 0.246, P < 0.003), systolic blood pressure (r = 0.370, P < 0.001) and diastolic blood pressure (r = 0.389, P < 0.001). Conclusions: The results indicated the application potential of IVP in assessing the early detection of cardiac function changes noninvasively and sensitively. The correlation with myocardial stiffness warrants further studies to substantiate its potential clinical utility.

Quantitative Assessment of Right Ventricular Function in Patients With Systemic Lupus Erythematosus Using the Novel Non-invasive Pressure-Strain Loop.

OBJECTIVE: Current echocardiography evaluation of right ventricular (RV) function, which heralds the prognosis in patients with systemic lupus erythematosus (SLE), is of limited utility. The non-invasive pressure-strain loop (PSL), an emerging technique, has been found to feasible, sensitive and accurate in the diagnosis of cardiovascular diseases. The aim of this study was to quantitatively evaluate, using the non-invasive PSL, the right ventricular myocardial work (RVMW) in SLE patients. METHODS: Seventy-five SLE patients were recruited and grouped by pulmonary artery systolic pressure (PASP) into normal (group A, N = 26), mild (group B, N = 22) and moderate to severe (group C, N = 27) groups. Twenty-five healthy volunteers undergoing physical examination were recruited as the control group. Right ventricular global myocardial work index (RVGWI), global constructive work (RVGCW), global wasted work (RVGWW), global work efficiency (RVGWE), global longitudinal strain (RVGLS) and other conventional parameters were measured. DISCUSSION: There were no differences between group A and the control group with respect to RVLS, RVGLS and all RVMW parameters (all p values > 0.05). RVGWI and RVGCW significantly differed among the other groups (all p values < 0.05). RVGWE was significantly lower and RVGWW was significantly higher in group C than in the control group and groups A and B (all p values < 0.05). Compared with the control group, RVGWW was significantly increased and RVGLS was significantly decreased in group B (all p values < 0.05). All but one RVMW parameter moderately to strongly correlated with SLE disease activity index (SLEDAI) and World Health Organization Functional Class (WHO-FC). RVGWW (area under the receiver operating characteristic curve [AUC] = 0.893) and RVGWE (AUC = 0.877) were sensitive parameters in detecting earlier cardiac dysfunction in SLE patients. CONCLUSION: RVGWW and RVGWE serve as sensitive and promising parameters in the integrative analysis of early right ventricular dysfunction in SLE patients. To conclude, non-invasive PSL, the novel method, facilitates the quantitative assessment of RVMW in SLE patients.

Caliber of Intracranial Arteries as a Marker for Cerebral Small Vessel Disease.

Background: The dilation of intracranial large arteries caliber, may transfer more hemodynamic burden to the downstream brain capillaries, which, in the long run, results in cerebral small vessel disease (CSVD). This study aimed to investigate the relationship between intracranial artery calibers and small vessel disease. Methods: Patients with first-ever ischemic stroke of lacunar infarction subtype were enrolled via Nanjing Stroke Registry Program. An intracranial arterial Z-score, named the brain arterial remodeling (BAR) score, was calculated by averaging the calibers of the seven main intracranial arteries. Among the enrolled patients, those with a BAR score < -1 SD were deemed to have small intracranial artery calibers; those with a BAR score >1 SD were deemed to have large intracranial artery calibers and those with a between BAR score were deemed to have normal intracranial artery calibers. Imaging markers of CSVD, including lacuna, white matter hyperintensity (WMH), enlarged perivascular spaces (EPVS) and cerebral microbleeds (CMBs) were rated and then summed to obtain a total CSVD score. Results: A total of 312 patients were involved in this study, patients with BAR score >1 SD were older (P = 0.039), and more prone to having a history of myocardial infarction (P = 0.033). The Spearman's rank correlation coefficient between the BAR score and total CSVD score is 0.320 (P < 0.001). Binary logistic regression found that BAR score >1 SD was correlated with lacuna (OR = 1.987; 95% CI, 1.037-3.807; P = 0.039); severe WMH (OR = 1.994; 95% CI, 1.003-3.964; P = 0.049); severe EPVS (OR = 2.544; 95% CI, 1.299-4.983; P = 0.006) and CSVD (OR = 2.997; 95% CI 1.182-7.599; P = 0.021). Ordinal logistic regression analysis found that age (OR = 1.028; 95% CI, 1.007-1.049; P = 0.009), hypertension (OR = 3.514; 95% CI, 2.114-5.769; P < 0.001) and BAR score >1 SD (OR = 2.418; 95% CI, 1.350-4.330; P = 0.003) were correlated with the total CSVD score. Conclusions: Patients with large intracranial arterial calibers may have heavier CSVD burden. The mechanisms of this association warrant further study.

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.

The Impacts of Peptic Ulcer on Stroke Recurrence.

BACKGROUND: Peptic ulcer has been associated with an increased risk of stroke. This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and mortality. SUBJECTS AND METHODS: Patients with first-ever ischemic stroke were retrospectively confirmed with or without a history of peptic ulcer. The primary end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method. Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox proportional hazards model. RESULTS: Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal stroke recurrence within 1 year of the index stroke was higher in patients with peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030). Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95% confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI 1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111-3.091, P = .018) were associated with stroke recurrence. CONCLUSIONS: Ischemic stroke patients with peptic ulcer may have an increased risk of stroke recurrence. The results emphasize the importance of appropriate prevention and management of peptic ulcer for secondary stroke prevention.

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.

Prediction of favorable outcome by percent improvement in patients with acute ischemic stroke treated with endovascular stent thrombectomy.

Our objective was to investigate a method for assessing early improvement and its predictive value for 3-month functional outcome in patients treated with EST. A total of 97 consecutive AIS patients undergoing EST were prospectively collected and retrospective reviewed. Data on demographics, vascular risk factors, admission National Institutes of Health Stroke Scale (NIHSS) score, 24-h NIHSS score, reperfusion and collateral formation were collected. Percent improvement was defined as ([baseline NIHSS score-24-h NIHSS score]/baseline NIHSS score×100%), while absolute improvement was calculated by the difference between scores (baseline NIHSS score-24-h NIHSS score). A 3-month functional outcome was assessed using the modified Rankin Scale (mRS). Favorable outcome was defined as a mRS score of 0-2. Areas under the receiver-operating characteristic (ROC) curve (AUC) for percent improvement and absolute improvement in predicting favorable outcome was compared. Finally, we investigated the independent predictors of improvement at 24h after EST and its relationship with favorable outcome. Pairwise comparison of ROC curves revealed that percent improvement had larger AUC than absolute improvement (p=0.004). Rapid neurological improvement (RNI), defined as percent improvement ⩾30%, was a powerful predictor of favorable outcome (odds ratio [OR] 7.63, confidence interval [CI]: 2.65-21.96; p<0.001). Good collaterals (OR 2.86; 95% CI: 1.11-7.38; p=0.030) and short onset-to-reperfusion time (ORT) (OR 3.02, 95% CI: 1.17-7.80; p=0.022) were independent predictors of RNI. RNI predicted 3-month favorable outcome in AIS patients treated with EST. Good collaterals and short ORT are independent predictors of RNI.

Hypertension unawareness among Chinese patients with first-ever stroke.

BACKGROUND: The low rates of hypertension treatment and control, partly due to its unawareness, are the main causes of the high stroke incidence in China. The purpose of this study was to evaluate hypertension unawareness amongst patients with first-ever stroke and to detect factors associated with its unawareness. METHODS: We selected those diagnosed with hypertension from patients with first-ever stroke registered in the Nanjing Stroke Registry Program between 2004 and 2014. These hypertensives were divided as being aware or unaware of their hypertension by using a brief questionnaire conducted shortly after the stroke. Multivariate logistic regression analysis was performed to identify potential factors associated with hypertension unawareness. RESULTS: Of the 5309 patients with first-ever stroke, 3732 (70.3%) were diagnosed with hypertension. Among which, 593 (15.9%) were unaware of their hypertension at the time of stroke onset. Lower-level of education (primary school or illiteracy) and smoking were associated positively with hypertension unawareness; while advanced age, overweight, diabetes mellitus, heart diseases and family history of stroke were associated negatively with hypertension unawareness. Annual data analyzed indicated that the rate of hypertension awareness increased during the past 11 years (r = 0.613, P = 0.045 for trends). CONCLUSIONS: A substantial proportion (15.9%) of Chinese patients with hypertension had not been aware of this covert risk until an overt stroke occurred. Hypertension unawareness was associated with lower educational levels and smoking, which address the importance of health education especially in these individuals.

Association of C7673T polymorphism in apolipoprotein B gene with ischemic stroke in the Chinese population: a meta-analysis.

BACKGROUND: Epidemiological studies have evaluated the association between the C7673T polymorphism in apolipoprotein B (apoB) gene and ischemic stroke (IS), but the results are still debatable even in the Chinese population. This meta-analysis was therefore designed to clarify these controversies. METHODS: All of the relevant studies were identified from PubMed, Embase, Chinese National Knowledge Infrastructure database and Chinese Wanfang database up to 31 October 2014. Statistical analyses were conducted with Revman 5.2 and STATA 12.0 software. Odds ratio (OR) with 95% confidence interval (CI) values were applied to evaluate the strength of the association. A fixed or random effect model was selected for pooling data based on the heterogeneity test. Publication bias was assessed by Begg's test and Egger's test. RESULTS: A significant association was found between the C7673T polymorphism in apoB gene and IS under the heterozygous genetic model (OR = 1.868, 95% CI = 1.160-3.007) and the allelic genetic model (OR = 1.742, 95% CI = 1.294-2.346), respectively. In the subgroup analysis by the geographic region, T allele could increase the risk of IS in northern Chinese (OR = 2.359, 95% CI: 1.425-3.907), but not in southern Chinese individuals (OR = 1.485, 95% CI: 0.778-2.832). Further stratification for source of controls showed that statistical significance was found among the population-based studies. CONCLUSION: Our meta-analysis revealed that C7673T polymorphism in apoB gene was significantly associated with increased IS risk in the Chinese population.

Reconfiguration of the Carotid Artery after Angioplasty and Stenting: A Case Report and Review of the Literature.

Severe carotid stenosis or occlusion may cause insufficient blood flow and lead to distal artery wall collapse and extensive lumen contraction. Whether this 'adaptive narrowing' can restitute after carotid recanalization is unclear. We report a patient with global ischemia due to occlusions of bilateral carotid and right vertebral arteries. The occluded left carotid was recanalized successfully with angioplasty and stenting. The adaptively narrowed distal carotid did not restitute immediately but regained its morphology 1 week after the procedure. Carotid adaptive narrow distal occlusion or stenosis may not regain its original morphology immediately but several days after recanalization. This knowledge is instructive for treating occlusive carotid diseases.

Telephone-based cognitive screening for stroke patients in China.

BACKGROUND: Valid telephone assessment for cognitive impairment is lacking in stroke settings. We investigated the feasibility and validity of the 5-minute National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) protocol and six-item screener (SIS) in stroke patients by telephone administration. METHODS: Patients were assessed with a comprehensive face-to-face neuropsychological assessment after three months of stroke onset, followed by the 5-minute NINDS-CSN protocol (30 points) and SIS (6 points) at least one month later. Administration time was recorded for the telephone tests. Validity of both tests was determined using the area under the receiver operating characteristics curve (AUC). RESULTS: Eighty-nine patients (age, 62.9 ± 8.6 years; male, 65.2%) received a face-to-face assessment and 80 completed telephone tests. The time required to administer the 5-minute NINDS-CSN protocol was 4.3 ± 1.0 minutes, and SIS 57.3 ± 17.7 seconds. Validity of detecting cognitive impairment as assessed by AUC was 0.86 (95% CI, 0.78-0.94) for 5-minute NINDS-CSN protocol, and 0.74 (95% CI, 0.63-0.85) for SIS. Sensitivity and specificity were optimal with the cut-off values of 23.5/24 for the 5-minute NINDS-CSN protocol, and 4/5 for SIS. CONCLUSIONS: Both the telephone-based 5-minute NINDS-CSN protocol and SIS were feasible and valid in screening cognitive impairment after stroke in China.

Chromosome 9p21.3 Variants Are Associated with Cerebral Infarction in Chinese Population.

Common variants of chromosome 9p21.3 associated with coronary disease have been established, but the association of 9p21.3 and cerebral infarction (CI) is not consistent. The aim of this study is to confirm the association of cerebral infarction and 9p21.3 in a Chinese Han population. This is a hospital-based case-control study, which involves 769 patients and 682 healthy controls. Eight single-nucleotide polymorphisms (SNPs) associated with cerebral infarction in previous literatures were genotyped and analyzed. The association analyses were performed at both SNP and haplotype levels. Three (rs2383207, rs1537378, and rs3731245) of eight SNPs were associated with cerebral infarction. In an allelic association analysis, rs2383207, rs3731245, and rs1537378 were significantly associated with CI; the odd ratios were 1.18 (95 % confidence interval (CI) = 1.01-1.37, P = 0.04), 1.29 (95 % CI = 1.06-1.56, P = 0.01), and 1.30 (95 % CI = 1.05-1.60, P = 0.02), respectively. rs1537378 remains significantly associated with CI independent of traditional cerebrovascular risk factors in a recessive model (odds ratio (OR) = 1.35, 95 % CI = 1.06-1.71, P = 0.013, Q = 0.03) and in an additive model (OR = 1.38, 95 % CI = 1.11-1.71, P = 0.004, Q = 0.02); conversely, rs2383207 (OR = 1.28, 95 % CI = 1.03-1.59, P = 0.02, Q = 0.03) and rs3731245 (OR = 1.31, 95 % CI = 1.05-1.65, P = 0.02, Q = 0.03) were significantly different in a recessive model. Haplotype analysis showed that the protective effect for haplotype AATAA remained significant (OR = 0.87, 95 % CI = 0.73-1.00, P = 2.99 × 10(3), Q = 2.15 × 10(3)). These findings showed that chromosome 9p21.3 is an important susceptibility locus for cerebral infarction in Chinese population.

Variant recurrent risk among stroke patients with different CYP2C19 phenotypes and treated with clopidogrel.

Polymorphisms of CYP2C19 have been associated with variant risk of subsequent cardiovascular events in survivors of myocardial infarction (MI) receiving clopidogrel. This study evaluated the impacts of CYP2C19 polymorphisms on stroke recurrence and other vascular events in a cohort of Chinese patients receiving clopidogrel. From Nanjing Stroke Registry Program, 625 consecutive patients with ischemic stroke were enrolled between May 2008 and April 2010. CYP2C19 variants (*2, *3, and *17) were genotyped. Clinical outcomes were determined with three monthly follow-up. The primary endpoint was a composite of vascular death, non-fatal ischemic stroke, and non-fatal MI. The second endpoint was bleeding events. The median exposure to clopidogrel was 13.2 (interquartile range, 8.9-18.0) months. Primary endpoint was observed in 85 (13.6%) patients and secondary endpoint in 13 (2.1%) patients. Frequencies of CYP2C19*1, *2, *3, and *17 alleles were 61.2, 34.0, 3.8, and 1.0%, respectively, in this patient cohort. CYP2C19 loss-of-function allele (*2 and *3, LOF) carriers were observed with higher risk of subsequent vascular events compared with non-carriers (17.2 versus 8.1%, HR = 2.16, 95% CI: 1.31-3.56, p = 0.003). After adjusted for age, sex, major cardiovascular risk factors, and drug agent, CYP2C19 LOF carrier was independently associated with primary endpoint (HR = 2.31, 95% CI: 1.39-3.84, p = 0.001). No significant association between CYP2C19 gain-of-function (*17, GOF) and clinical events was detected. In Chinese stroke survivors treated with clopidogrel, carriers of CYP2C19 LOF allele may have increased risk of recurrence.

Argatroban for preventing occlusion and restenosis after extracranial artery stenting.

BACKGROUND/AIMS: Restenosis following extracranial artery stenting is a limitation that affects long-term outcomes. Effective and satisfying pharmacological strategies in preventing restenosis have not been established. This study aimed to evaluate whether argatroban, a direct thrombin inhibitor, could reduce the risk of in-stent restenosis after extracranial artery stenting. METHODS: One hundred and fourteen patients hospitalized between August 2010 and August 2011 were enrolled. Patients were randomly assigned to argatroban (n = 58) and blank control groups (n = 56). The patients in the argatroban arm were treated with 10 mg of intravenous argatroban twice daily 2 days before and 3 days after the stenting procedures. Patients were followed for 12 months after the procedure. During follow-up, restenosis and target revascularization were analyzed. Recurrent cerebrovascular and cardiovascular events and deaths were also compared between the groups. RESULTS: One patient in the stenting group withdrew immediately after the procedure due to unsuccessful stenting. Restenosis occurred in 4 patients (7.4%) in the argatroban group and in 11 patients (21.6%) in the control group during the 6- to 9-month angiographic follow-up period (p = 0.032). Nine months after the procedures, argatroban-treated patients had a trend towards a lower incidence of target revascularization compared with the controls (5.4 vs. 13.7%, p = 0.188). No major bleeding events or other adverse events occurred in the argatroban group. CONCLUSION: This pilot clinical trial is the first that uses argatroban to prevent restenosis in ischemic cerebrovascular disease, and suggests that intravenous administration of argatroban is effective and safe in preventing restenosis after extracranial artery stenting. Larger randomized controlled clinical trials are warranted.

Keep warm and get success: the role of postischemic temperature in the mouse middle cerebral artery occlusion model.

Intraluminal suture middle cerebral artery occlusion (MCAO) model is the most frequently used model for ischemic stroke. However, the success rate of this model is variable among different research studies. This study aimed to investigate the effect of postischemic temperature on the success rate. A total of 100 C57BL/6 mice were randomized into two groups: control group (n=50), body temperature was allowed to self-regulate after MCAO; temperature-controlled group (n=50), mice were kept warm in an incubator for 12 h after MCAO. The body temperature of animals was measured before, during, and for 12 h after MCAO. Neurological deficits and infarct volumes were measured at 24 h after MCAO. There was significant difference (P<0.05) of the body temperature between the two groups from 0.5 h to 3.5 h post ischemia. Moreover, there was obvious difference between the success rates of the two groups (control group: 52%, temperature-controlled group: 84%, P<0.05). In the successful models, infarct volume was significantly (P<0.05) higher in temperature-controlled group (53.44%±9.83%, n=42) than control group (45.63%±10.24%, n=26). There was significant difference of the modified neurological severity scores (P<0.05), left adhesive tests (P<0.05) between the two groups. Our data demonstrated that postischemic warming contributed to the success of mouse MCAO model.

Co-culturing improves the OGD-injured neuron repairing and NSCs differentiation via Notch pathway activation.

Neural stem cell (NSC) transplantation for ischemic stroke is expected to repair the neuronal injury and replace the lost neurons through cell-cell cross talk between injured neurons and the transplanted NSCs. Here, we set up an in vitro co-culturing system of oxygen-glucose deprivation (OGD) injured neurons and NSCs to investigate the neuronal repairing effect and effects on NSCs differentiation. We focused on the Notch1 pathway as a possible mediator of these effects. OGD-injured neurons induced increased activation of Notch1 in co-cultured NSCs, through the up-regulations of the DLL1, the Notch1 intracellular domain (NICD) and the down-stream genes Hes1/5. When the NSCs were pre-treated with the Notch pathway inhibitor DAPT, the activation of Notch1 was blocked, lower NSCs differentiation was detected and the neurotrophic effect was also abolished. As shown by the novel co-culturing system, the NSCs co-cultured with OGD injured neurons were induced to differentiate through the Notch1 pathway activation; and these induced NSCs showed greater potential to support both the repair of injured neurons and form new neurons.

Cell based therapies for ischemic stroke: from basic science to bedside.

Cell therapy is emerging as a viable therapy to restore neurological function after stroke. Many types of stem/progenitor cells from different sources have been explored for their feasibility and efficacy for the treatment of stroke. Transplanted cells not only have the potential to replace the lost circuitry, but also produce growth and trophic factors, or stimulate the release of such factors from host brain cells, thereby enhancing endogenous brain repair processes. Although stem/progenitor cells have shown a promising role in ischemic stroke in experimental studies as well as initial clinical pilot studies, cellular therapy is still at an early stage in humans. Many critical issues need to be addressed including the therapeutic time window, cell type selection, delivery route, and in vivo monitoring of their migration pattern. This review attempts to provide a comprehensive synopsis of preclinical evidence and clinical experience of various donor cell types, their restorative mechanisms, delivery routes, imaging strategies, future prospects and challenges for translating cell therapies as a neurorestorative regimen in clinical applications.

Dietary fiber consumption and risk of stroke.

Observational studies suggest an association between dietary fiber consumption and risk of stroke, but the results are inconclusive. The authors conducted a meta-analysis of prospective cohort studies to evaluate the relation between dietary fiber consumption and stroke risk and mortality. Relevant studies were identified by searching PubMed, Embase, and ISI Web of Science through February 2013. We included prospective studies that reported relative risks (RRs) with 95 % confidence intervals (CIs) for the association between dietary fiber consumption and stroke risk and mortality. Both fixed- and random-effects models were used to calculate the summary risk estimates. Eleven prospective studies involving 325,627 participants were included in the meta-analysis. The pooled RR of stroke for the highest compared with the lowest dietary fiber consumption was 0.83 (95 % CI 0.74, 0.93). In addition, the increment in dietary fiber consumption was associated with decreased stroke risk in a dose-response manner. Sensitivity analysis restricted to studies with control for conventional risk factors yielded similar results, and omission of any single study had little effect on the combined risk estimate. Moreover, there was a trend toward an inverse association between higher fiber consumption and stroke mortality (RR 0.85; 95 % CI 0.60, 1.20), although it is not significant. This meta-analysis indicated that dietary fiber consumption is inversely associated with stroke risk, and the effect is probably independent of conventional risk factors. Our results support recommendations for higher consumption of fiber-rich foods to prevent stroke.