Safety and Efficacy of Reteplase Versus Alteplase for Acute Ischemic Stroke: A Phase 2 Randomized Controlled Trial.

BACKGROUND: Reteplase is a more affordable new-generation thrombolytic with a prolonged half-life. We aimed to determine the safety dose range of reteplase for patients with acute ischemic stroke within 4.5 hours of onset. METHODS: This is a multicenter, prospective, randomized controlled, open-label, blinded-end point phase 2 clinical trial. Patients with acute ischemic stroke aged between 18 and 80 years who were eligible for standard intravenous thrombolysis were enrolled from 17 centers in China and randomly assigned (1:1:1) to receive intravenous reteplase 12+12 mg, intravenous reteplase 18+18 mg, or intravenous alteplase 0.9 mg/kg. The primary safety outcome was symptomatic intracranial hemorrhage (SITS definition) within 36 hours. The primary efficacy outcome was the proportion of patients with the National Institutes of Health Stroke Scale score of no more than 1 or a decrease of at least 4 points from the baseline at 14 days after thrombolysis. RESULTS: Between August 2019 and May 2021, 180 patients were randomly assigned to reteplase 12+12 mg (n=61), reteplase 18+18 mg (n=67), or alteplase (n=52). Four patients did not receive the study agent. Symptomatic intracranial hemorrhage occurred in 3 of 60 (5.0%) in the reteplase 12+12 mg group, 1 of 66 (1.5%) in the reteplase 18+18 mg group, and 1 of 50 (2.0%) in the alteplase group (P=0.53). The primary efficacy outcome in the modified intention-to-treat population occurred in 45 of 60 (75.0%) in the reteplase 12+12 mg group (odds ratio, 0.85 [95% CI, 0.35-2.06]), 48 of 66 (72.7%) in the reteplase 18+18 mg group (odds ratio, 0.75 [95% CI, 0.32-1.78]), and 39 of 50 (78.0%) in alteplase group. CONCLUSIONS: Reteplase was well tolerated in patients with acute ischemic stroke within 4.5 hours of onset in China with a similar efficacy profile to alteplase. The efficacy and appropriate dosage of reteplase for patients with acute ischemic stroke need prospective validation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04028518.

Enhancing clinical awareness: retrospective analysis of neurosyphilis cases and diagnostic predictors for early recognition and treatment.

OBJECTIVE: This is a retrospective analysis of clinical data from individuals diagnosed with neurosyphilis, aiming to enhance healthcare professionals' understanding of the disease and expedite early diagnosis and intervention. METHODS: A retrospective analysis was conducted on the clinical records of 50 patients who received a diagnosis of symptomatic neurosyphilis and were admitted to the Neurology Department during the period spanning January 2012 to December 2022. RESULTS: Clinical manifestations encompassed diverse phenotypes, with syphilitic meningitis accounting for 16% of cases, characterized by symptoms such as headache, blepharoptosis, paralysis, blurred vision, and tinnitus. Meningovascular syphilis presented in 36% of cases, exhibiting episodic loss of consciousness, limb numbness, and limb convulsion. Paralytic dementia manifested in 36% of cases, featuring symptoms such as memory loss, sluggish response, and slow movement. Tabes dorsalis was observed in 12% of cases, presenting with weakness, numbness, and staggering. Routine cerebrospinal fluid (CSF) analysis indicated abnormal white blood cell counts in 60% of patients, while biochemical testing revealed abnormal protein content in 52% of patients. Notably, statistically significant differences were observed between patients with interstitial and parenchymatous neurosyphilis (Z = 2.023, P = 0.044) in terms of CSF protein content. Electroencephalogram (EEG) results were abnormal in six patients, and imaging studies unveiled diverse findings in 46 patients. CONCLUSION: The study highlights the importance of neurological and/or ocular symptoms in diagnosing symptomatic neurosyphilis. Individuals with hypomnesia should be closely monitored for potential neurosyphilis. Integrating clinical manifestations, laboratory tests, EEG, and imaging can reduce misdiagnosis. This comprehensive approach shows promise in improving early identification and management of neurosyphilis.

Association between Fibrinogen-to-Albumin Ratio and Adverse Stroke Outcomes among Patients with Acute Ischemic Stroke.

INTRODUCTION: Fibrinogen-to-albumin ratio (FAR) is implicated in prothrombotic states and is associated with an increased risk of acute ischemic stroke (AIS). However, studies investigating whether the prothrombotic effect of FAR is associated with long-term adverse outcomes in patients with AIS are lacking. Therefore, we aimed to investigate the association based on The Third China National Stroke Registry (CNSR-III). METHODS: Patients with AIS with complete laboratory data for fibrinogen and albumin in the CNRS-III were included in this study. The primary outcomes were poor functional outcomes (modified Rankin scale score 3-6) at 12 months, including disability (modified Rankin scale score 3-5), all-cause death, recurrent stroke, and combined vascular events within 1 year. Univariate and multivariate logistic or Cox regression analyses were used to investigate the association between FAR quartiles and adverse outcomes. RESULTS: A total of 8984 patients with AIS were enrolled in this study. After one-year follow-up, 238 patients were lost to follow-up. A total of 1230(14.06%) patients had poor functional outcomes; 932(10.37%) and 981(10.92%) experienced stroke recurrence and combined vascular events, respectively. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the highest quartile of the FAR(>11.44) were 1.64(1.35-2.00) for poor functional outcomes, 1.68(1.34-2.10) for disability, 1.40(1.02-1.94) for all-cause death, 1.11(0.92-1.34) for stroke recurrence, and 1.11(0.92-1.33) for combined vascular event, respectively. CONCLUSION: High FAR(>11.44) increased the risk of short- and long-term poor functional outcomes, including disability and all-cause death among patients with AIS. The FAR may play an important role in the early stratification of patients with AIS.

Independent Predictive Value of Elevated YKL-40 in Ischemic Stroke Prognosis: Findings from a Nationwide Stroke Registry.

INTRODUCTION: Elevated circulatory concentrations of YKL-40 have been reported in patients with ischemic stroke. This study further investigated the association of plasma YKL-40 concentrations at admission and short, long-term prognosis after ischemic stroke. METHODS: Based on a prospective, nationwide multicenter registry focusing consecutive patients of ischemic stroke and transient ischemic attack, plasma YKL-40 levels were detected by enzyme-linked immunosorbent assay at admission, and patients were stratified into percentile according to the plasma YKL-40 concentrations. The multivariate Cox or logistic regression model was used to investigate the association of YKL-40 concentration with death and functional outcomes at 3 months, 6 months, and 12 months after ischemic stroke, with potential confounders adjusted. RESULTS: A total of 8,006 first-ever ischemic stroke patients, with the age of 61.7 ± 11.5, were included in this study. The mortality of 0-33%, 34-66%, 67-90%, and 91-100% groups at 12 months follow-up was 0.9%, 2.2%, 4.4%, and 9.4%, respectively (p < 0.0001), and the modified Rankin Scale 3-6 ratio was 6.8%, 10.5%, 15.7%, and 24.0%, respectively (p < 0.0001). In the multivariate regression, after adjusting for potential confounders, 91-100% group had higher risk of death (hazard ratio 2.99, 95% confidence interval 1.75-5.11)and modified Rankin Scale 3-6 (odds ratio 1.42, 95% confidence interval 1.08-1.88) at 12 months since onset of ischemic stroke compared to the 0-33% group. CONCLUSIONS: The elevated YKL-40 at admission can potentially help predict death, functional prognosis after ischemic stroke, which may help further studies to explore the potential physiological and pathological mechanism including the effects of vulnerable plaque and collateral circulation.

Prevalence and Prognostic Significance of Malnutrition Risk in Patients With Acute Ischemic Stroke: Results From the Third China National Stroke Registry.

BACKGROUND AND PURPOSE: To investigate the prevalence of malnutrition risk in patients with acute ischemic stroke (AIS) at admission, the association between malnutrition risk and long-term outcomes, and whether the predictive ability would be improved after adding to previous prognostic models for poor outcomes. METHODS: Based on the Third China National Stroke Registry data from August 2015 to March 2018, we evaluated malnutrition risk using objective scores, including the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index. The primary outcome was death or major disability (modified Rankin Scale score ≥3) at 1 year after stroke onset. We calculated the crude prevalence of malnutrition risk and investigated the association between malnutrition risk and clinical outcomes. Prognostic performance of 3 objective malnutrition scores for poor outcomes was assessed. RESULTS: Moderate to severe malnutrition risk was identified in 5.89%, 5.30%, and 1.95% of the Third China National Stroke Registry AIS patients according to the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index, respectively. At 1-year follow-up, 1143 participants (13.5%) experienced death or major disability. After adjustment for traditional risk factors, moderate to severe malnutrition risk was associated with high risk of composite events (odds ratio, 2.25 [95% CI, 1.75-2.90], for controlling nutritional status score; odds ratio, 2.10 [95% CI, 1.63-2.69], for geriatric nutritional risk index; odds ratio, 3.36 [95% CI, 2.33-4.84], for prognostic nutritional index; all P<0.01). Addition of the 3 malnutrition scores to different predicted scales (iScore and Acute Stroke Registry and Analysis of Lausanne) improved predictive ability for long-term poor outcomes validated by the integrated discrimination index (all P<0.05). CONCLUSIONS: The prevalence of moderate or severe malnutrition risk in Chinese patients with AIS ranged from 1.95% to 5.89%. Malnutrition risk in patients with AIS was associated with increased risk of long-term death and major disability. Our study provides evidence supporting the prognostic significance of objective malnutrition scores after AIS.

Association between haemoglobin A1c and cerebral microbleeds in community-based stroke-free individuals: A cross-sectional study.

AIMS: The association between haemoglobin A1c (HbA1c) and cerebral microbleeds (CMBs) remains unclear. We aimed to investigate the association between HbA1c and CMBs in community-based individuals without stroke or transient ischaemic attack (TIA) and whether the association differs between individuals with and without diabetes mellitus (DM). MATERIALS AND METHODS: All individuals were recruited from a community in Beijing, China, from January 2015 to September 2019. All individuals completed a questionnaire and underwent blood tests and brain magnetic resonance imaging. A susceptibility-weighted imaging sequence was acquired to detect CMBs, which were defined as small, round and low-signal lesions with <10 mm diameter. The association between HbA1c and CMBs was analysed using multivariable logistic regression adjusted for demographics, medical history and blood sample test results. Subgroup analyses stratified by history of DM were performed. RESULTS: Of 544 recruited individuals, 119 (21.88%) had CMBs. HbA1c was independently associated with CMBs (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.03-2.22). In 87 individuals with DM, multivariable logistic analysis showed that HbA1c was significantly associated with CMBs (OR, 1.67; 95% CI, 1.04-2.69), whereas in individuals without DM, no significant association was observed between HbA1c and CMBs (OR, 1.07; 95% CI, 0.50-2.30). CONCLUSIONS: HbA1c was associated with CMBs in individuals without stroke or TIA, particularly in individuals with DM, suggesting that the status of glycaemic control warrants attention for the prevention of CMBs. It would be beneficial to manage HbA1c specifically to control the risk of CMBs, especially in individuals with DM.

A novel nutritional index and adverse outcomes in ischemic stroke: Results from the third China National Stroke Registry.

BACKGROUND AND AIMS: Few studies have applied the triglyceride, cholesterol, body weight index (TCBI) in acute ischemic stroke (AIS). We investigated the association between the TCBI and adverse clinical outcomes in patients with AIS. METHODS AND RESULTS: Based on the Third China National Stroke Registry (CNSR-III) data from August 2015 to March 2018, we evaluated the nutritional status of patients with AIS using the TCBI. Patients were categorized according to quartile levels of the TCBI. The main outcomes were poor functional outcomes and recurrent stroke at 1-year and secondary outcomes were adverse outcomes at 3 and 6 months after stroke onset. Poor functional outcomes consisted of all-cause mortality and major disabilities. Multivariate analyses with logistic or Cox regression analysis and restricted cubic splines determined the association between the TCBI and adverse outcomes. We included 9708 patients. At the 1-year follow-up, 1323 patients (13.6%) had died or experienced major disability. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the lowest quartile at 1-year were 1.47 (1.22-1.78) for poor functional outcomes, 1.46 (1.18-1.81) for major disability, and 1.34 (0.94-1.86) for all-cause mortality. Kaplan-Meier analysis demonstrated an inverse relationship between all-cause mortality and the TCBI (log-rank p < 0.05). An approximately L-shaped relationship between TCBI levels and poor functional outcomes and major disability was observed at 1-year. CONCLUSION: The novel TCBI was associated with short- and long-term adverse outcomes in AIS. Thus, it may be useful for predicting adverse outcomes in patients with AIS.

Reduction of cerebral blood flow in community-based adults with subclinical cerebrovascular atherosclerosis: A 3.0T magnetic resonance imaging study.

Reduction in cerebral blood flow (CBF), one of the major metrics for cerebral perfusion, is associated with many brain disorders. Therefore, early characterization of CBF prior to occurrence of symptoms is essential for prevention of cerebral ischemic events. We hypothesized that large artery atherosclerosis might be a potential indicator for decline in cerebral perfusion. The aim of this study was to investigate the relationship between large artery atherosclerosis and CBF in asymptomatic adults. A total of 134 asymptomatic subjects (mean age, 56.2 ±â€¯12.8 years; 54 males) were recruited and underwent magnetic resonance (MR) imaging for brain and intracranial and extracranial carotid arteries. Presence or absence of cerebrovascular atherosclerosis was determined on MR vessel wall images. The CBF was measured with pseudo-continuous arterial spin labeling (pCASL) imaging. The CBF values in internal carotid artery (ICA) (37.2 ±â€¯5.8 vs. 39.0 ±â€¯4.9 ml/100 g/min, P = 0.049) and vertebrobasilar artery (VA-BA) territories (42.0 ±â€¯6.8 vs. 44.8 ±â€¯7.0 ml/100 g/min, P = 0.023) were significantly reduced in subjects with cerebrovascular plaque compared to those without. Presence of cerebrovascular plaque was significantly associated with CBF of VA-BA territory before (odds ratio, 2.89; 95% confidence interval, 1.37-6.08; P = 0.005) and after adjusted for confounding factors including age, gender, body-mass-index, diabetes, systolic blood pressure, hyperlipidemia and history of cardiovascular disease (odds ratio, 2.76; 95% confidence interval, 1.18-6.46; P = 0.019). In conclusion, presence of cerebrovascular atherosclerosis is independently associated with reduction in CBF measured by pCASL in asymptomatic adults, suggesting that cerebrovascular large artery atherosclerosis might be an effective indicator for impairment of cerebral microcirculation hemodynamics.

Risk Factors for Pressure Sores in Hospitalized Acute Ischemic Stroke Patients.

BACKGROUND: Acute ischemic stroke patients are a group at high risk for pressure sores. It is important to identify risk factors for pressure sores in acute ischemic stroke patients in order to facilitate early adoption of appropriate preventive and treatment measures. METHODS: Data were derived from the China National Stroke Registry. Acute ischemic stroke patients aged >18 years who presented at the hospital within 14 days after the onset of symptoms were eligible for this study. Comprehensive baseline data were collected. The definition of pressure sores was based on assessment at discharge of whether the patient had pressure sores at any time during hospitalization. RESULTS: 12,415 patients with a mean age of 67 years and a mean length of hospitalization of 14 days were included in the study. Among these patients, 97 (0.8%) had pressure sores during hospitalization. In the multivariate analysis of risk factors for pressure sores, age (each increment of 5 years), being unmarried, NIHSS at admission (each increment of 3 points), mRS at admission (3-5 points), diabetes mellitus, hemoglobin at admission (each incremental reduction of 10 units), and history of peripheral vascular disease all were significantly correlated with the occurrence of pressure sores among acute ischemic stroke patients during hospitalization. CONCLUSIONS: Old age, severe neurological disability, being unmarried, low hemoglobin, and history of diabetes mellitus and peripheral vascular disease were risk factors for pressure sores in acute ischemic stroke patients.

Association Between Carotid Atherosclerotic Plaque Calcification and Intraplaque Hemorrhage: A Magnetic Resonance Imaging Study.

OBJECTIVE: Carotid intraplaque hemorrhage (IPH) is associated with cardiovascular events. Calcification, which frequently accompanies IPH, may play a role in IPH occurrence. In this study, we aimed to investigate the associations between calcification characteristics and IPH in carotid plaques. APPROACH AND RESULTS: One hundred seventeen patients with cerebrovascular symptoms and carotid plaques detected by ultrasound were recruited and underwent multicontrast magnetic resonance imaging. Advanced carotid plaques with composition measured by magnetic resonance imaging were included in the analysis. Carotid calcifications were divided into the following categories: surface, mixed, and deep calcification. They were also classified into single and multiple calcifications according to quantity. Logistic regression models utilizing generalized estimating equations were performed to evaluate the relationship between calcification and IPH. Of 117 subjects, 85 with 142 plaques were included in the final analysis, whereas 32 were excluded because of lack of plaque compositions. Of the 142 plaques, 40 (28.2%) had IPH. Plaques with IPH showed greater prevalence of calcification than those without (87.5% versus 55.9%; P=0.005). After adjusting for age, low-density lipoprotein, maximum wall thickness, and maximum soft plaque thickness, multiple calcifications (odd ratio, 10.1; 95% confidence interval, 3.3-30.4), surface calcification (odd ratio, 29.4; 95% confidence interval, 4.1-210.8), and mixed calcifications (odd ratio, 27.9; 95% confidence interval, 7.3-107.1) were found to be strongly associated with the presence of IPH (all P<0.05). CONCLUSIONS: Surface calcification and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of IPH, suggesting that both quantity and location of calcification may play important roles in the occurrence of IPH. These findings may provide novel insights for understanding mechanisms of IPH.

Socioeconomic and lifestyle factors associated with HPV infection in pregnant women: a matched case-control study in Beijing, China.

BACKGROUND: Human papillomavirus (HPV) infection plays key role in the development of cervical cancer. The purpose of this study was to investigate socioeconomic and lifestyle factors associated with HPV infection in pregnant women in Beijing, China. METHODS: An age matched case-control study designed with 66 women as the case group (HPV positive) and 132 women as the control group (HPV negative) was carried out in two hospitals in Beijing. Socioeconomic and lifestyle factors were obtained using a standard questionnaire. Cervical cells from study subjects were collected for HPV detection. An unconditional logistic regression model with backward stepwise selection was performed to predict the odds ratio (OR) and 95% confidence interval (CI) for the significant factors associated with HPV infection. RESULTS: The analyses of present data show that alcohol consumption during pregnancy was the strongest significant factor (OR = 3.35, 95% CI = 1.40-8.03, p = 0.007) when comparing the case (HPV positive) group with the control (HPV negative) group. There were no statistical differences observed in any of the socioeconomic factors when comparing the case and control groups. CONCLUSION: The results of this study may help to prevent HPV infection in China by providing evidence to support improving the national policy on alcohol restriction and introducing public health interventions, especially for pregnant women in Beijing.

Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Hematoma Expansion of Intracerebral Hemorrhage.

BACKGROUND: Hematoma expansion is an independent risk factor of unfavorable outcome after intracerebral hemorrhage (ICH), which always occurs in the early phase after symptoms onset. The relationship between underlying small vessel disease (SVD) and hematoma expansion was inconsistent in patients with ICH. We aimed to investigate the relationship between magnetic resonance (MR) characteristics of SVD and hematoma expansion in patients with ICH within 72 hours after symptoms onset. METHODS: Data were derived from a cohort of biological sample collection from April 2014 to April 2016. We recruited patients aged 18 years or older with a baseline and follow-up computed tomography within 72 hours after symptom onset, as well as an MR imaging within 3 months before or after ICH. Hematoma expansion was defined as an increase in volume between baseline and final hematoma volume exceeding 6 mL or 33% of the baseline volume. Multivariate logistic regression was used to explore the association between clinical characteristics, imaging markers, total SVD score, and hematoma expansion in patients with ICH. RESULTS: A total of 103 patients experienced hematoma expansion among the 263 enrolled patients (mean age 53.4 ± 14.0 years, 76.4% male). Electrocardiogram abnormal rhythm, fewer non-lobar microbleeds, lower plasma homocysteine concentration, and smaller baseline hematoma volume independently predicted the risk of hematoma expansion (P = .004, .021, .001, and .024, respectively). Odds ratios ranged from 1.02 to 3.72. CONCLUSIONS: Our study suggested that the use of MR markers revealing underlying SVD may help to identify patients with ICH with potential hematoma expansion.

Current smoking is associated with extracranial carotid atherosclerotic stenosis but not with intracranial large artery disease.

BACKGROUND: Accumulating evidence has shown that cigarette smoking is an important risk factor for ischemic stroke. However, it is not clear about the potential mechanisms through which cigarette smoking affects stroke risk. In the study, we aimed to investigate the relationship between cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS). METHODS: We analyzed patients enrolled in the Chinese intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. For those patients with current smoking, data on time duration (year) and extent (the number of cigarette smoked per day) was recorded and pack year of smoking was calculated. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS. RESULTS: A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9 ± 11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR = 1.47, 95% CI = 1.09-1.99, P < 0.01). In addition, with 1 year of smoking increment, the risk of ECAS increased by 1.1% (adjusted OR = 1.011; 95% CI = 1.003-1.019; P = 0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR = 1.010; 95% CI = 1.001-1.020; P = 0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR = 1.007; 95% CI = 1.002-1.012; P < 0.01). However, no significant association was found between smoking status and the occurrence of ICAS. CONCLUSION: A dose-response relationship was identified between cigarette smoking and the occurrence of ECAS, but not ICAS. Further studies on molecular mechanisms were warranted.

External Validation of Pooled Cohort Risk Equations to Predict 1-Year Clinical Outcome in Ischemic Stroke Patients.

BACKGROUND The present study aimed to validate the pooled cohort risk (PCR) equations in a Chinese ischemic stroke population and to explore its prognostic value in predicting stroke recurrence, coronary heart disease, and vascular death. MATERIAL AND METHODS Patients were selected from the China National Stroke Registry. The C statistic was used to examine the clinical prediction of the scores. To analyze the relevant risk factors, univariate and multivariate logistic regressions were performed. RESULTS Out of a total of 22 216 patients, 8287 patients (including 7652 acute ischemic stroke [AIS] and 635 transient ischemic attack [TIA] patients) were selected and enrolled in the study. At 1-year follow-up, for stroke recurrence rate, the C statistic value was 0.584 in AIS patients and 0.573 in all patients. For non-fatal myocardial infarction, the C statistic value was 0.533 in AIS patients and 0.493 in all patients. For vascular death, the C statistic value was 0.592 in AIS patients and 0.592 in all patients. For all events, the C statistic value was 0.582 in AIS patients and 0.575 in all patients. For AIS patients, the 12-month cumulative rates for recurrent stroke, vascular death, and combined vascular events were higher in the high-PCR group (PCR ≥20%). CONCLUSIONS Pooled cohort risk equations may serve as potential tools to predict and stratify the 1-year risk of recurrent stroke and combined vascular events in AIS/TIA patients in China.

External Validation of the Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale Score for Predicting Pneumonia After Stroke Using Data From the China National Stroke Registry.

BACKGROUND AND PURPOSE: Pneumonia is an important risk factor for mortality and morbidity after stroke. The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score was shown to be a useful tool for predicting stroke-associated pneumonia based on UK multicenter cohort study. We aimed to externally validate the score using data from the China National Stroke Registry (CNSR). METHODS: Eligible patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) in the CNSR from 2007 to 2008 were included. The area under the receiver operating characteristic (AUC) curve was used to evaluate discrimination. The Hosmer-Lemeshow goodness of fit test and Pearson correlation coefficient were performed to assess calibration of the model. RESULTS: A total of 19,333 patients (AIS = 14400; ICH = 4933) were included and the overall pneumonia rate was 12.7%. The AUC was .76 (95% confidence interval [CI]: .75-.78) for the subgroup of AIS and .70 (95% CI: .68-.72) for the subgroup of ICH. The Hosmer-Lemeshow test showed the ISAN score with the good calibration for AIS and ICH (P = .177 and .405, respectively). The plot of observed versus predicted pneumonia rates suggested higher correlation for patients with AIS than with ICH (Pearson correlation coefficient = .99 and .83, respectively). CONCLUSIONS: The ISAN score was a useful tool for predicting in-hospital pneumonia after acute stroke, especially for patients with AIS. Further validations need to be done in different populations.

Co-existing intracranial and extracranial carotid artery atherosclerotic plaques and recurrent stroke risk: a three-dimensional multicontrast cardiovascular magnetic resonance study.

BACKGROUND: As a systemic disease, atherosclerosis commonly affects intracranial and extracranial carotid arteries simultaneously which is defined as co-existing plaques. Previous studies demonstrated that co-existing atherosclerotic diseases are significantly associated with ischemic cerebrovascular events. The aim of this study was to investigate the characteristics of co-existing intracranial and extracranial carotid atherosclerotic plaques and their relationships with recurrent stroke by using 3D multi-contrast magnetic resonance (MR) vessel wall imaging. METHODS: Patients with recent cerebrovascular symptoms in anterior circulation and at least one carotid plaque were recruited. All patients underwent cardiovascular magnetic resonance (CMR) for brain and intracranial and extracranial arteries. Presence/absence of atherosclerotic plaque at each arterial segment was identified. The maximum wall thickness (Max WT), length, stenosis of each plaque was measured. The presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) was assessed. Cerebral old and acute infarcts in anterior circulation were evaluated. RESULTS: Fifty-eight patients (mean age: 58.0 ± 8.5 years old, 34 males) were recruited. Of the 58 patients, co-existing intracranial and extracranial carotid artery plaques were found in 45 patients (77.6%), of which 7 (15.6%) had first time acute stroke and 26 (57.8%) had recurrent stroke. For these 33 patients with stroke, the number of intracranial plaques (OR = 11.26; 95% CI, 1.27-100; p = 0.030) and co-existing intracranial and extracranial carotid artery plaques (OR = 2.42; 95% CI, 1.04-5.64; p = 0.040) was significantly associated with recurrent stroke. After adjusting for traditional risk factors, the number of co-existing plaques was still significantly correlated with recurrent stroke (OR = 3.31; 95% CI, 1.09-10.08; p = 0.035). No correlations were found between recurrent stroke and Max WT, length, stenosis, and compositions of plaques. CONCLUSIONS: Co-existing intracranial and extracranial carotid artery plaques are prevalent in symptomatic patients and the number of co-existing plaques is independently associated with the risk of recurrent stroke.

Association between 5,10-Methylenetetrahydrofolate Reductase C677T Gene Polymorphism and Risk of Ischemic Stroke: A Meta-analysis.

BACKGROUND: Hyperhomocysteinemia, a condition that is strongly determined by dietary intake of B vitamins, has been suggested to be an independent risk factor for ischemic stroke (IS). To test this hypothesis, we performed a meta-analysis to investigate the associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which plays a critical role in modulating plasma homocysteine concentrations, and IS risk. MATERIALS AND METHODS: We searched case-control studies on the association between MTHFR C677T genetic polymorphism and susceptibility to IS through PubMed, Embase, and Medline databases from January 2000 up to October 2014. The random-effects model was employed because moderate heterogeneity across studies was observed, as assessed by I(2) statistic. Publication bias was estimated using funnel plot and Egger's regression test. RESULTS: A total of 22 case-control studies were included in the current meta-analysis. Significant associations between MTHFR C677T genetic polymorphism and IS were found under the dominant model (pooled odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.24-1.57), the recessive model (pooled OR = 1.37, 95% CI: 1.16-1.61), and the allele model (pooled OR = 1.29, 95% CI: 1.18-1.42). CONCLUSIONS: The meta-analysis suggests that MTHFR C677T genetic polymorphism is significantly associated with susceptibility to IS, which provides evidence supporting hyperhomocysteinemia as a risk factor for stroke.

A Comparison of Mortality Prognostic Scores in Ischemic Stroke Patients.

OBJECTIVE: Our objective is to compare the predictive accuracy of 4 recently established stroke mortality scores in the Chinese population, including the Get With The Guidelines-Stroke risk score, the iScore prediction rule for 30-day mortality, the iScore prediction rule for 1-year mortality, and the PLAN score. METHODS: We analyzed data from 9698 hospitalized patients with acute ischemic stroke in the China National Stroke Registry (September 2007-August 2008). Outcome measures were in-hospital mortality, 30-day mortality, and 1-year mortality. To evaluate the performance of each model, we calculated the area under the receiver operating characteristic curve. The areas under the curve (AUCs) were compared using the z-test. RESULTS: Among 9698 patients, the mean age was 65.5 years and 38.6% were female. Overall in-hospital mortality, 30-day mortality, and 1-year mortality were 3.0%, 5.9%, and 14.6%, respectively. The AUC values of 4 scores for each outcome were all more than .75. The z-test did not show significant difference among the AUC values of these 4 scores. For patients who received thrombolysis therapy, these 4 scores had apparent reductions in the AUC values. CONCLUSIONS: We could confirm the predictive value of all these 4 scores for short-term and long-term mortalities in Chinese IS patients. However, these 4 scores need to be interpreted with caution in the patients who received thrombolysis therapy.

External Validation of the Totaled Health Risks in Vascular Events Score to Predict Functional Outcome and Mortality in Patients Entered into the China National Stroke Registry.

BACKGROUND: THRIVE (Totaled Health Risks in Vascular Events) score is a tool used to predict the functional outcome and mortality in patients with ischemic stroke at 3 months. This project aims to explore its prognostic value at 3, 6, and 12 months in Chinese stroke patients. METHODS: We applied the THRIVE score in 11,064 patients with acute ischemic stroke who were entered into the China National Stroke Registry. We applied the THRIVE score and examined its performance on mortality and poor functional outcome (modified Rankin Scale score between 3 and 6). Model discrimination was measured by c-statistic. Calibration was assessed by comparing predicted and observed probability of poor outcome or mortality by using Pearson correlation coefficient. RESULTS: Among the 11,064 patients with ischemic stroke, the mortality rates at discharge, and at 3, 6, and 12 months were 3.6%, 7.9%, 10.5%, and 12.7%, respectively; the corresponding c-statistics were .83(95% confidence interval [CI], .80-.86), .79(95% CI, .77-.81), .80(95% CI, .78-.81), and .79(95% CI, .78-.80), respectively. For the poor functional outcome at discharge, and at 3, 6, and 12 months, the c-statistics were .74(95% CI, .73-.75), .76(95% CI, .75-.77), .76(95% CI, .75-.77), and .77(95% CI, .76-.78), respectively. The observed and expected probability of poor functional outcome and mortality based on the THRIVE score correlated (Pearson correlation coefficient ranged from .90 to .99) highly. CONCLUSIONS: The THRIVE score is a reliable tool to predict the mortality and to fairly predict the functional outcome at discharge, and at 3, 6, and 12 months in Chinese patients after acute ischemic stroke.

Impaired glucose regulation predicted 1-year mortality of Chinese patients with ischemic stroke: data from abnormal glucose regulation in patients with acute stroke across China.

BACKGROUND AND PURPOSE: It remains uncertain if impaired glucose regulation (IGR) as a predictor for stroke outcomes. This study aimed at observing the effect of IGR on the 1-year outcomes in Chinese patients with ischemic stroke. METHODS: Patients with acute ischemic stroke were recruited consecutively in multihospitals across China. Oral glucose tolerance test was performed to identify IGR. Cox proportion hazard model was performed to investigate the effect of IGR on 1-year mortality or stroke recurrence in patients with ischemic stroke. RESULTS: The study recruited 2639 patients with ischemic stroke. IGR was shown as an independent risk factor for the mortality of patients with ischemic stroke (hazard ratio [95% confidence interval], 3.088 [1.386-6.884]; P=0.006). However, IGR showed no significant effects on the dependency or stroke recurrence of patients (P=0.540 and 0.618, respectively). CONCLUSIONS: IGR was an independent predictor for the mortality of patients with ischemic stroke. IGR should be highlighted and intervened actively in the patients with ischemic stroke.