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Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxyprogesterone (17α-OH-progesterone) to 11-deoxycortisol. More than 100 CYP21A2 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of WT human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH-progesterone). We found that the 17α-OH-progester-one- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions. Twelve P450 21A2 variants associated with either salt-wasting or nonclassical forms of CAH were expressed, purified, and analyzed. The catalytic activities of these 12 variants ranged from 0.00009% to 30% of WT P450 21A2 and the extent of heme incorporation from 10% to 95% of the WT. Substrate dissociation constants (Ks) for four variants were 37-13,000-fold higher than for WT P450 21A2. Cytochrome b5, which augments several P450 activities, inhibited P450 21A2 activity. Similar to the WT enzyme, high noncompetitive intermolecular kinetic deuterium isotope effects (≥ 5.5) were observed for all six P450 21A2 variants examined for 21-hydroxylation of 21-d3-progesterone, indicating that C-H bond breaking is a rate-limiting step over a 104-fold range of catalytic efficiency. Using UV-visible and CD spectroscopy, we found that P450 21A2 thermal stability assessed in bacterial cells and with purified enzymes differed among salt-wasting- and nonclassical-associated variants, but these differences did not correlate with catalytic activity. Our in-depth investigation of CAH-associated P450 21A2 variants reveals critical insight into the effects of disease-causing mutations on this important enzyme. [ABSTRACT FROM AUTHOR]

Computing a bijective spherical parametrization of a genus-0 surface with low distortion is a fundamental task in geometric modeling and processing. Current methods for spherical parametrization cannot, in general, control the worst case distortion of all triangles nor guarantee bijectivity. Given an initial bijective spherical parametrization, with high distortion, we develop a non-linear constrained optimization problem to refine it, with objective penalizing the presence of triangles degeneration and maximal distortion. By using a dynamic adjusting parameter and a constrained, iterative inexact block coordinate descent optimization method, we efficiently and robustly achieve a bijective and low distortion parametrization with an optimal sphere radius. Compared to the state-of-the-art methods, our method is robust to initial parametrization and not sensitive to parameter choice. We demonstrate that our method produces excellent results on numerous models undergoing simple to complex shapes, in comparison to several state-of-the-art methods. [ABSTRACT FROM AUTHOR]

The hemoglobin of sea worm Amphitrite ornata, which for historical reasons is abbreviated as DHP for dehaloperoxidase, has two physiological functions: it binds dioxygen in the ferrous state and dehalogenates halophenols, such as 2,4,6-trichlorophenol (TCP), using hydrogen peroxide as the oxidant in the ferric state. The crystal structures of three DHP variants (Y34N, Y34N/S91G, and L100F) with TCP bound show two mutually exclusive modes of substrate binding. One of them, the internal site, is deep inside the distal pocket with the phenolic OH moiety forming a hydrogen bond to the water molecule coordinated to the heme Fe. In this complex, the distal histidine is predominantly located in the closed position and also forms a hydrogen bond to the phenolic hydroxide. The second mode of TCP binding is external, at the heme edge, with the halophenol molecule forming a lid covering the entrance to the distal cavity. The distal histidine is in the open position and forms a hydrogen bond to the OH group of TCP, which also hydrogen bonds to the hydroxyl of Tyr38. The distance between the Cl4 atom of TCP and the heme Fe is 3.9 Å (nonbonding). In both complexes, TCP molecules prevent the approach of hydrogen peroxide to the heme, indicating that the complexes are inhibitory and implying that the substrates must bind in an ordered fashion: hydrogen peroxide first and TCP second. Kinetic studies confirmed the inhibition of DHP by high concentrations of TCP. The external binding mode may resemble the interaction of TCP with Compound I, the catalytic intermediate to which halophenols bind. The measured values of the apparent Km for TCP were in the range of 0.3–0.8 mM, much lower than the concentrations required to observe TCP binding in crystals. This indicates that during catalysis TCP binds to Compound I. Mutant F21W, which likely has the internal TCP binding site blocked, has ~7% of the activity of wild-type DHP. [ABSTRACT FROM AUTHOR]

Stroke care in China was less developed than in western countries but great headway has been made in recent years through unremitting efforts by a group of local neurologists working in this field. [ABSTRACT FROM AUTHOR]

In the present study, the Eastern Star ferry accident was analyzed via 24Model. 24Model, as an accident causation model based on system thinking, holds that all causations of the accident are hazards and all hazards in the system need to be identified and comprehensively controlled in accident prevention. The result showed that five factors were the main causes of the accident. First, the direct causes: bad weather, the bad condition of the hull and the unsafe acts of the captain. Second, the indirect cause: the lack of safety awareness and safety knowledge of both the captain and the company's senior management. Third, there were loopholes in safety management system, including the training, supervision and execution of the company. Forth, the root cause: the company didn't establish a good safety culture. Last, the external causes: the severe market pressure, excessive regulatory authorities with puzzled relations and responsibilities--seriously hindered effective supervision. In order to prevent this kind of accident and to secure shipping system, the shipping companies and the relevant regulatory units should draw lessons from the five factors mentioned above, and take measures to identify and control those hazards. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether the fasting glucose level on admission, day 14 or their variation in patients with aSAH was associated with 1-year mortality. Methods: A prospective study was undertaken to analyze the effects of fasting glucose on admission, day 14 and their variation on the 1-year mortality rate after aSAH. Patients with aSAH were enrolled to assess the mortality rate relationship with fasting glucose, medical history, clinical and radiological grades. Multivariate Cox regression analysis was performed to assess risk factors for 1-year mortality. Results: A total of 239 aSAH patients without history of diabetes were followed up, with the 1-year mortality being 11.7%. Admission glucose levels were found to be associated with 1-year mortality after being adjusted for other confounding factors in Cox regression (HR: 1.524 per mmol/L; 95%CI, 1.250-1.859). Within 14 days, fasting glucose levels of 85 patients had increased. Patients who died also exhibited higher levels of glucose (dead vs. survival: 61.54% vs. 33.66%, p < 0.01). In addition, higher blood glucose levels were associated with an elevated 1-year mortality (HR: 1.350 per mmol/L; 95%CI, 1.153-1.580). Conclusions: Glucose levels at admission as well as their variation after aSAH are predictive of an elevated 1-year mortality rate. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the effect of metabolic syndrome (MetS) on prognosis of ischemic stroke secondary to intracranial stenosis in Chinese patients. Methods: A prospective cohort of 701 patients with ischemic stroke, caused by intracranial stenosis, were followed at 3- month intervals for 1 year to monitor development of recurrent stroke or death. Imaging was performed using magnetic resonance angiography. MetS was defined using International Diabetes Federation (IDF) criteria. Results: MetS was identified in 26.0% of the cohort of stroke patients. Patients with MetS were more likely to be female, nonsmokers, and more likely to have a prior history of diabetes mellitus, high blood glucose and a family history of stroke than patients without MetS. During 1-year follow-up, patients with MetS had a non-significantly higher rate of stroke recurrence (7.1%) than patients without MetS (3.9%; P = 0.07). There was no difference in mortality (3.3% versus 3.5%, respectively). Multivariate Cox proportional hazards analysis (adjusting for gender, BMI, smoking, diabetes, and LDL-C) identified an association between that 1-year stroke recurrence and the presence of MetS (hazard ratio 2.30; 95% CI: 1.01- 5.22) and large waist circumference (hazard ratio: 2.39; 95% CI: 1.05-5.42). However, multivariable analysis adjusting for the individual components of MetS found no significant associations between MetS and stroke recurrence. There were no associations between these parameters and mortality. Conclusions: Chinese patients with symptomatic intracranial atherosclerosis who have MetS, are at higher risk of recurrent stroke than those without MetS. However, MetS was not predictive of stroke recurrence beyond its individual components and one-year mortality. [ABSTRACT FROM AUTHOR]

Intracranial atherosclerosis burden is an arising key index for the risk and prognosis for Intracranial Atherosclerosis Stenosis (ICAS). The present study estimated one-year prognosis for patients of symptomatic ICAS with different degrees of intracranial atherosclerosis burden (ICASB) and identified whether the category of multiple and single acute infarction was associated with atherosclerosis burden. A total of 2864 consecutive patients, from 22 hospitals across China, who experienced an acute cerebral ischemia <7 days after onset of symptoms were evaluated. All patients underwent magnetic resonance angiography, and the degree of intracranial stenosis with the ICASB was calculated. The patients were categorized into three groups according to ICASB grading: <4, 4-5 and >5scores. Multivariate Cox proportional hazards regression models were used to estimate the impact of the hazard ratios(HR) of the putative determinants of recurrent stroke in one year. In the groups with ICASB 4-5 and ICASB >5scores recurrent stroke were significantly higher than the other (P<0.0001). On multivariate logistic analysis, ICASB (4-5) indicated more stroke recurrence at 12 months (adjusted hazard ratio, 1.96; 95% confidence interval, 1.08-3.56; P=0.027), compared to the ICASB<4scores and >5 groups (P<0.001). Moreover, proportion of single and multiple infarction lesions differs with different ICASB. Multiple lesions were related with higher of ICASB(P<0.001). Intracranial atherosclerosis burden was associated with recurrent stroke at 12 months. Multiple infarction lesions were associated with higher ICASB score which indicate higher risk of recurrent. [ABSTRACT FROM AUTHOR]

Leukoaraiosis (LA) is frequently found in ischemic stroke patients, especially when those patients have intracranial atherosclerosis (ICAS). However, previous studies regarding an association of LA with cerebral large artery atherosclerosis showed conflicting results, and the relationship of LA with ICAS is uncertain. This study aimed to explore the association between LA and cerebral large artery atherosclerosis in Chinese patients with cerebral ischemia. Data were derived from the Chinese Intracranial Atherosclerosis (CICAS) study. Patients diagnosed with an ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset were included. The analysis of magnetic resonance imaging (MRI) focused on severity of LA in periventricular and deep white matter; type of cerebral large artery stenosis; and the number, severity, and distribution of ICAS lesions. ICAS was defined as an occlusion or more than 50% stenosis of intracranial vessels on magnetic resonance angiography. Among 2420 patients included, distinct LA was observed in 898 (37.11%) patients, and the rate of LA increased significantly with an increased number of risk factors. Multivariate analysis revealed that LA was independently associated with ICAS (odds ratio [OR], 1.388; 95% confidence interval [CI], 1.132-1.702; P=0.0016). In the subgroup analysis of ICAS, LA was more frequently observed in multiple lesions (OR, 1.342; 95% CI, 1.060-1.699; P=0.0146), occlusive lesions (OR, 1.554; 95% CI, 1.214-1.998; P=0.0005), and lesions in the posterior circulation (OR, 1.360; 95% CI, 1.003-1.846; P=0.0481). In this nationwide prospective study, LA was associated with symptomatic ICAS, patients with multiple ICAS lesions, occlusive lesions, and atherosclerotic lesions in the posterior circulation were more likely to coexist with LA. [ABSTRACT FROM AUTHOR]

Human activity on arid lands has been related to oases evolution. The ancient Loulan, an important transportation hub of the ancient Silk Road, developed on an ancient oasis on the west bank of the lake Lop Nur in Xinjiang, China. Previous studies and historical documents suggest that the region has experienced dramatic natural environmental and human activity--related changes over time, transitioning from a particularly prosperous oasis to a depopulated zone with harsh environment after about 1500 a BP (before present, where present = AD 1950). Based on systematic radiocarbon (14C) dating for natural plant remains and archeological sites in the Loulan area, it was revealed that the region re-experienced oasis environment from 1260 to 1450 cal. AD, corresponding to the Yuan--Ming Dynasties, which is the climate transition stage from the 'Medieval Warm Period' to the 'Little Ice Age', encompassing a series of pulse-like flood events which cannot be identified from lacustrine deposition due to the limits of sampling resolution and dating. It was found that humans re-occupied the Loulan area and built canals to irrigate farmlands during the period. The more habitable hydrological conditions that resulted from these environmental changes present one major reason for the re-emergence of human activities in the Loulan area. [ABSTRACT FROM AUTHOR]

Background: Stroke rehabilitation improves functional recovery among stroke patients. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation among patients with acute ischemic stroke. Aims: We examined the frequency and determinants of an assessment for rehabilitation among acute ischemic stroke patients from the China National Stroke Registry II. Methods: Data for 19,294 acute ischemic stroke patients admitted to 219 hospitals from June 2012 to January 2013 were analyzed. The multivariable logistic regression model with the generalized estimating equation method accounting for in-hospital clustering was used to identify patient and hospital factors associated with having a rehabilitation assessment during the acute hospitalization. Results: Among 19,294 acute ischemic stroke patients, 11,451 (59.4%) were assessed for rehabilitation. Rates of rehabilitation assessment varied among 219 hospitals (IQR 41.4% vs 81.5%). In the multivariable analysis, factors associated with increased likelihood of a rehabilitation assessment (p<0.05) included disability prior to stroke, higher NIHSS on admission, receipt of a dysphagia screen, deep venous thrombosis prophylaxis, carotid vessel imaging, longer length of stay, and treatment at a hospital with a higher number of hospital beds (per 100 units). In contrast, patients with a history of atrial fibrillation and hospitals with higher number of annual stroke discharges (per 100 patients) were less likely to receive rehabilitation assessment during the acute stroke hospitalization. Conclusions: Rehabilitation assessment among acute ischemic stroke patients was suboptimal in China. Rates varied considerably among hospitals and support the need to improve adherence to recommended care for stroke survivors. [ABSTRACT FROM AUTHOR]

Background: Conflicting results on the correlation between hyperuricemia and the prognosis of stroke had been reported and the close association between serum uric acid (SUA) and abnormal glycomatabolism might further complicate the assessment of the correlation. We aimed to investigate SUA in predicting the prognosis of acute stroke in different glycometabolism status.Methods: A total of 2907 patients aged from 18 to 85 (1220 diabetes mellitus (DM), 777 prediabetes and 910 normoglycemia) were selected from the Abnormal Glucose Regulation in Patients with Acute Stroke across China (ACROSS-China) study. The patients were divided into groups according to the SUA quartile as well as decile. The correlations between SUA and the poor outcome (mRS > 2) at discharge were assessed stratified by glucose metabolism status. Multivariate logistic regression was used to analyze the potential risk factors of poor in-hospital outcome of stroke and the risk-adjustment of the correlation between SUA and the prognosis of stroke. P < 0.05 was considered statistically significant.Results: SUA were divided first as Quartile1 to 4 (Quartile1 < 221 μmol L-1; Quartile2 (221-286) μmol L-1; Quartile3 (286-352) μmol L-1 and Quartile4 > 352 μmol L-1), then as decile1 to 10. In normoglycaemia, SUA quartiles, deciles and continuous SUA concentration were independently significantly associated with poor outcome. Q1 was independently associated with the higher possibility of poor functional outcome (compared to Q4, odds ratios (ORs) with 95% confidential interval (CI) was 3.79 (1.23-8.67) in Q1); Lower level of SUA in DM was also associated with poor functional outcome at discharge compared to the highest level of SUA(Q4)(OR with 95% CI, 2.07 (1.05-4.08)), however, lower SUA level was also related to severer stroke at admission in DM as well as in prediabetes (P < 0.001 in DM and 0.023 in prediabetes) and severer stroke resulted in worse functional outcome at discharge (OR with 95% CI, 12.15 (8.08-18.21) in DM and 11.58 (7.50-23.25) in prediabetes). But in normoglycamic stroke, SUA levels did not differ in stroke severity at admission (P = 0.066).Conclusions: Low SUA level (<221 μmol L-1) independently and strongly predicts the short-term poor functional outcome in acute stroke with normoglycaemia other than diabetes or prediabetes. [ABSTRACT FROM AUTHOR]

Background: To investigate the relationship between baseline systolic blood pressure (SBP) and visit-to-visit blood pressure variability in a general population.Methods: This is a prospective longitudinal cohort study on cardiovascular risk factors and cardiovascular or cerebrovascular events. Study participants attended a face-to-face interview every 2 years. Blood pressure variability was defined using the standard deviation and coefficient of variation of all SBP values at baseline and follow-up visits. The coefficient of variation is the ratio of the standard deviation to the mean SBP. We used multivariate linear regression models to test the relationships between SBP and standard deviation, and between SBP and coefficient of variation.Results: Approximately 43,360 participants (mean age: 48.2±11.5 years) were selected. In multivariate analysis, after adjustment for potential confounders, baseline SBPs <120 mmHg were inversely related to standard deviation (P<0.001) and coefficient of variation (P<0.001). In contrast, baseline SBPs ≥140 mmHg were significantly positively associated with standard deviation (P<0.001) and coefficient of variation (P<0.001). Baseline SBPs of 120-140 mmHg were associated with the lowest standard deviation and coefficient of variation. The associations between baseline SBP and standard deviation, and between SBP and coefficient of variation during follow-ups showed a U curve.Conclusion: Both lower and higher baseline SBPs were associated with increased blood pressure variability. To control blood pressure variability, a good target SBP range for a general population might be 120-139 mmHg. [ABSTRACT FROM AUTHOR]

Importance: Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel.Objective: To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack.Design, Setting, and Participants: Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012.Interventions: Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone.Main Outcomes and Measures: The primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome.Results: Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction).Conclusions and Relevance: Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment.Trial Registration: clinicaltrials.gov Identifier: NCT00979589. [ABSTRACT FROM AUTHOR]

Background: Previous findings of the association between socioeconomic deprivation and mortality after ischemic stroke are inconsistent. There is a lack of data on the association with combined low education, occupational class, and income. We assessed the associations of three indicators with mortality. Methods: We examined data from the China National Stroke Registry, recording all stroke patients occurred between September 2007 and August 2008. Baseline socioeconomic deprivation was measured using low levels of education at <6 years, occupation as manual laboring, and average family income per capita at ≤¥1000 per month. A total of 12,246 patients with ischemic stroke were analyzed. Results: In a 12-month follow-up 1640 patients died. After adjustment for age, sex, cardiovascular risk factors, severity of stroke, and prehospital medications, odds ratio for mortality in patients with low education was 1.25 (95%CI 1.05-1.48), manual laboring 1.37 (1.09-1.72), and low income 1.19 (1.03-1.37). Further adjustment for acute care and medications in and after hospital made no substantial changes in these odds ratios, except a marginal significant odds ratio for low income (1.15, 0.99-1.33). The odds ratio for low income was 1.27 (1.01-1.60) within patients with high education. Compared with no socioeconomic deprivation, the odds ratio in patients with socioeconomic deprivation determined by any one indicator was 1.33 (1.11-1.59), by any two indicators 1.36 (1.10-1.69), and by all three indicators 1.56 (1.23-1.97). Conclusions: There are significant inequalities in survival after ischemic stroke in China in terms of social and material forms of deprivation. General socioeconomic improvement, targeting groups at high risk of mortality is likely to reduce inequality in survival after stroke. [ABSTRACT FROM AUTHOR]

Background: The Oxfordshire Community Stroke Project (OCSP) classification system is a simple stroke classification system that can be used to predict clinical outcomes. In this study, we compare the safety and efficacy of intravenous thrombolysis in Chinese stroke patients categorized using the OCSP classification system.Patients and Methods: We collected data from the Thrombolysis Implementation and Monitoring of Acute Ischemic Stroke in China registry. A total of 1,115 patients treated with intravenous thrombolysis with alteplase within 4.5 hours of stroke onset were included. Symptomatic intracranial hemorrhage (SICH), mortality, and 90-day functional outcomes were compared between the stroke patients with different stroke subtypes.Results: Of the 1,115 patients included in the cohort, 197 (17.67%) were classified with total anterior circulation infarct (TACI), 700 (62.78%) with partial anterior circulation infarct, 153 (13.72%) with posterior circulation infarct, and 65 (5.83%) with lacunar infarct. After multivariable adjustment, compared to the patients with non-TACI, those with TACI had a significantly increased risk of SICH (odds ratio [OR] 8.80; 95% confidence interval [CI] 2.84-27.25, P<0.001), higher mortality (OR 5.24; 95% CI 3.19-8.62; P<0.001), and poor functional independence (OR 0.38; 95% CI 0.26-0.56; P<0.001) at 3-month follow-up.Conclusion: After thrombolysis, the patients with TACI exhibited greater SICH, a higher mortality rate, and worse 3-month clinical outcomes compared with the patients with non-TACI. The OCSP classification system may help clinicians predict the safety and efficacy of thrombolysis. [ABSTRACT FROM AUTHOR]

Background: Stroke recurrence and disability in patients with a minor stroke is one of the most depressing medical situations. In this study, we aimed to identify which factors were associated with adverse outcomes of a minor stroke.Methods: The China National Stroke Registry (CNSR) is a nationwide prospective registry for patients presented to hospitals with acute cerebrovascular events between September 2007 and August 2008. The 3-month follow-up was completed in 4669 patients with a minor stroke defined as the initial neurological severity lower than 4 in the National Institutes of Health Stroke Scale (NIHSS). Multivariate model was used to determine the association between risk factors and clinical outcomes.Results: Of 4669 patients with a minor stroke during 3-month follow-up, 459 (9.8 %) patients experienced recurrent stroke, 679 (14.5 %) had stroke disability and 168 (3.6 %) died. Multivariate model identified hypertension, diabetes mellitus, atrial fibrillation, coronary heart disease and previous stroke as independent predictors for the recurrent stroke. Age, diabetes mellitus, atrial fibrillation, previous stroke and time from onset to admission < 24 h were independent predictors for stroke disability. The independent predictors for the all-caused death were age, atrial fibrillation, and coronary heart disease.Conclusions: The short-term risk of poor clinical outcome in Chinese patients with a minor stroke was substantial. Therefore, patients with a minor stroke should be given expeditious assessment and urgent aggressive intervention. [ABSTRACT FROM AUTHOR]

Objective: Questions exist regarding the causal relationship between malnutrition and stroke outcomes. This study aimed to determine whether nutritional status changes or malnutrition during hospitalisation could predict 3-month outcomes in acute stroke patients.Methods: During a 10-month period, patients who suffered their first stroke within 7 days after stroke onset were included in this prospective multi-centre study. The demographic parameters, stroke risk and severity factors, malnutrition risk factors and dysphagia were recorded. Nutritional status was assessed by 3 anthropometric and 3 biochemical indices. Changes in nutritional status were defined by comparing the admission values with the 2-week values. A Modified Rankin Scale score of 3-6 was defined as a poor outcome at the 3-month follow-up. Univariate and multiple logistic regression analyses were used to investigate the power of nutritional status changes in predicting poor patient outcomes.Results: Data from 760 patients were analysed. Poor outcomes were observed in 264 (34.7%) patients. Malnutrition prevalence was 3.8% at admission and 7.5% after 2-weeks in hospital, which could not predict 3-month outcome. Emerging malnutrition was observed in 36 patients (4.7%) during the 2-week hospitalisation period and independently predicted poor 3-month outcomes after adjusting for confounding factors (odds ratio 1.37, 95% confidence interval 1.03-1.83).Conclusions: Emerging malnutrition during hospitalisation independently predicted poor 3-month outcomes in acute stroke patients in this study. [ABSTRACT FROM AUTHOR]

Background--The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. Methods and Results--The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). Conclusions--The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. Clinical Trial Registration--URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. [ABSTRACT FROM AUTHOR]

Background The investigation of glycated hemoglobin (HbA1c) as a diagnostic tool for abnormal glycometabolism is lack in acute ischemic stroke patients in China and worldwide. This paper was aimed to determine whether HbA1c, fasting plasma glucose (FPG), or HbA1c combined with FPG, could be used to screen for diabetes mellitus (DM) or prediabetes in acute ischemic stroke patients without previous DM. Methods Acute ischemic stroke patients without previous DM (n = 1,316) were selected from the Abnormal gluCose Regulation in Patients with Acute StrOke acrosS China Study (ACROSSChina). Oral glucose tolerance test (OGTT), HbA1c, FPG, and HbA1c combined with FPG were used as the screening methods to categorize the glycometabolic status. OGTT was taken as the golden method. Venn diagrams and the overlap index were used to determine the associations among the three methods of identifying abnormal glycometabolism. The area under the receiver operating characteristic curve (AUROC) and Youden index were used to assess and compare the accuracy in detecting abnormal glycometabolism. Youden analyses were performed to determine the ideal cutoff values of HbA1c in diagnosing abnormal glycometabolism. Results In acute ischemic stroke patients without previous DM, the overlaps of HbA1c versus OGTT, HbA1c versus FPG, and all the three methods independently, were low for detecting abnormal glycometabolism (all <50%). HbA1c can significantly detect more cases of prediabetes than OGTT (P < 0.001). The combination of HbA1c and FPG significantly raised the sensitivity to over 60.0%, specificity to over 80.0%, and the diagnostic accuracy (Youden index from under 40.0% to 42.4%)for DM. HbA1c of 5.7%-6.4% had a low to moderate concordance with OGTT for identifying prediabetes (AUROC = 0.557, P = 0.001). HbA1c values of 6.3% and 5.9% were found to be the ideal cutoff values for detecting DM and abnormal glycometabolism in our data, respectively. Conclusions The combination of HbA1c and FPG increased the diagnostic rate of DM when compared with OGTT, and increased the diagnostic accuracy for DM compared with HbA1c or FPG alone. Our results advocate the use of HbA1c as screening tool for the diagnosis of prediabetes. [ABSTRACT FROM AUTHOR]

Background. The Functional Gait Assessment (FGA) is a validated measurement of gait-related activities in certain populations and may be potentially useful to assess balance and gait disorders in patients with Parkinson disease (PD). Objective. The purpose of this study was to determine the construct, concurrent, and predictive validity of the FGA in inpatients with PD. Design. This was a prospective cohort study. Methods. One hundred twenty-one inpatients with PD were prospectively enrolled. The FGA and other relevant appraisals of gait, balance, disease severity, and activities of daily living were performed. Six months later, the patients were interviewed by telephone to have their fall information collected. Principal component analysis was used to determine construct validity. Spearman correlation coefficients were used to determine concurrent validity between the FGA and other measures. Cutoff point, sensitivity, specificity, and positive likelihood ratio were calculated for predictive validity based on the receiver operating characteristic curve. Results. One common factor was extracted for construct validity, which cumulatively explained 64.0% of the total variance. Correlation coefficients for the FGA compared with other measures ranged from . 57 to .85. The cutoff point for predicting falls was 18, with sensitivity of 80.6%, specificity of 80.0%, and positive likelihood ratio of 4.03. Limitations. This study was limited by the length of time of follow-up and self-reports of falls without the requirement of a fall diary. Medication adjustment after the FGA evaluation may have led to a different cutoff score for identifying those patients who were at risk of falling. Conclusions. The FGA demonstrated good construct validity in patients with PD. It had moderate to strong correlations with other balance and gait appraisals. The FGA can be used to predict falls within the subsequent 6 months. [ABSTRACT FROM AUTHOR]

OBJECTIVE We aim to explore whether a link exists between different levels of estimated glomerular filtration rate (eGFR) and poor outcomes of acute stroke in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Between 2007 and 2009, 6,261 patients with cerebrovascular events and diabetes were included in the nal analysis from the China National Stroke Registry (CNSR) and substudy of CNSR (Abnormal Glucose Regulation in Patients with Acute Stroke Across China [ACROSS]).The period of follow-up was 1 year after stroke onset. eGFR was calculated with the Chinese modification of Chronic Kidney Disease ? Epidemiology Collaboration (CKD-EPI) equation. The association between eGFR and poor stroke outcomes, including all-cause death, recurrent stroke, combined end point (stroke or death), and stroke disability, was evaluated by multivariate analysis with the adjustment for demographic and clinical features. RESULTS Of 4,836 patients with stroke, low eGFR (<45 mL/min/1.73 m² ) occurred in 268 (5.5%) and high eGFR (≥120 mL/min/1.73 m ) in 387 (8.0%). The median value for eGFR in all patients was 92.6 mL/min/1.73 m². Low eGFR was independently associated with risks of all clinical outcomes in stroke/transient ischemic attack patients or patients with ischemic events, but not in patients with hemorrhagic stroke. Additionally, high eGFR was positively associated with an increased risk of adverse outcomes in all stroke subtypes, including hemorrhagic stroke. CONCLUSIONS Low and high eGFRs (<45 or ≥120 mL/min/1.73 m², respectively) are independent predictors of all-cause mortality and other poor outcomes after acute stroke in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article presents a study which discusses the efficiency of aspirin and clopidogrel as a combination therapy for providing protection against acute minor stroke or transient ischemic attack (TIA). Randomized controlled trial was applied to the study using placebo on patients who have undergone onset TIA. Results show that among TIA patients, the drug combination is more effective than aspirin alone.

Background: Antihypertensive treatment is recommended for secondary prevention in patients with ischemic stroke or transient ischemic attack. Prescription of and persistence with antihypertensives for secondary prevention is high in developed countries; whether this is true in China is unclear. The aim of this study was to describe the patterns of antihypertensive medication use, and factors associated with its use, 1 year after stroke in China. Methods: A total of 7880 hypertensive patients diagnosed with ischemic stroke or transient ischemic attack in the China National Stroke Registry were analyzed. Multivariate logistic regression was used to identify factors associated with antihypertensive medication use at discharge and 12 months. Results: Antihypertensive medication was used by 4458 (56.6%) participants at discharge and 2927 (37.1%) at 12 months. Calcium channel blockers were the most common among five classes of antihypertensive medication prescribed at discharge, and participants prescribed this class had the highest 1-year persistence. In-hospital health education was the strongest predictor of antihypertensive medication use at discharge; age and stroke severity were the strongest negative predictors of use at 12 months. Conclusion: Use of antihypertensive medication 1 year after stroke is extremely low in China. Intervention is needed to improve adherence to antihypertensive medication, especially for the elderly and severe stroke patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate the influence of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes in doctors' decisions to use antihypertensive prescriptions at discharge for ischemic stroke patients in a real-world setting. Methods: Using the China National Stroke Registry, we analyzed data from 12,063 hospitalized patients who had been diagnosed with ischemic stroke. The cause of ischemic stroke was classified according to the TOAST criteria. The information about the prescription of antihypertensive medication at discharge was extracted from medical records. Multivariate logistic regression was used to assess the impact of TOAST subtypes on the prescription of antihypertensive medication at discharge. Results: Multivariate analysis showed that, compared with large artery atherosclerosis patients with moderate (<70%) stenosis, large artery atherosclerosis patients with severe (⩾70%) stenosis or patients with stroke of undetermined etiology were less likely to be prescribed antihypertensive medication at discharge (odds ratio [OR], 0.72; 95% confidence interval [CI]: 0.59-0.88; OR, 0.71; 95% CI: 0.64-0.79), while patients with small artery occlusion were more likely to be prescribed antihypertensives (OR, 1.50; 95% CI: 1.33-1.69). Conclusion: The TOAST subtype is an important determinant of the prescription of antihypertensive medication for ischemic stroke patients at discharge in normal clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Metabolic syndrome has emerged as a novel risk factor in cardiovascular disease due to its potential for predicting stroke in population-based studies. We investigated the relationship of metabolic syndrome with stroke recurrence. Methods: This was a retrospective analysis of Chinese patients enrolled in the prospective Abnormal gluCose Regulation in patients with acute strOke acroSS China (ACROSS-China) study after their first ischemic stroke. Metabolic syndrome was defined using the International Diabetes Federation (IDF) criteria. Vascular risk factors were assessed. Outcome was defined as recurrence of stroke within one year after the index ischemic stroke. Cox proportional hazards regression was performed to identify potential predictors of stroke recurrence. Results: The prevalence of metabolic syndrome among 2639 ischemic stroke patients was 51.35%. During the one-year follow-up, 195 strokes (7.4%) recurred. The multivariate hazard ratio (95% CI) of stroke recurrence was 1.94 (1.39-2.73) for metabolic syndrome. After adjustment for components, metabolic syndrome lost its association with stroke recurrence; in this model, high fasting plasma glucose (IDF definition) was a predictor for stroke recurrence. Conclusion: Metabolic syndrome may not be predictive for stroke recurrence beyond its component individual factors for Chinese ischemic stroke patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the effect of stroke on poor functional outcome in ischemia attack in the previous issue.