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.

The MRI enhancement ratio and plaque steepness may be more accurate for predicting recurrent ischemic cerebrovascular events in patients with intracranial atherosclerosis.

OBJECTIVES: To assess the complementary value of high-resolution multi-contrast MRI (hrMRI) in identifying symptomatic patients with intracranial atherosclerosis (ICAS) who are likely to experience recurrent ischemic cerebrovascular events. METHODS: In this retrospective cohort study, eighty patients with acute ischemic events attributed to ICAS who underwent hrMRI examination between January 2015 and January 2019 were included. Median follow-up for all patients was 30 months (range: 1 to 52 months) and recurrent ischemic cerebrovascular events were recorded. Cox regression analysis and time-dependent ROC were performed to quantify the association between the plaque characteristics and recurrent events. RESULTS: During the follow-up, 14 patients experienced recurrent ischemic cerebrovascular events. Young males and those with diabetes and poor medication persistence were more likely to experience recurrent events. ICAS in patients with recurrence had significantly higher enhancement ratio and steepness which is defined as the ratio between the plaque height and length than those without (p < 0.001 and p = 0.015, respectively). After adjustment of clinical factors, enhancement ratio (HR, 13.13 [95% CI, 3.58-48.20], p < 0.001) and plaque steepness (HR, 110.27 [95% CI, 4.75-2560.91], p = 0.003) were independent imaging biomarkers associated with recurrent events. Time-dependent ROC indicated that integrated high enhancement ratio and steepness into clinical risk factors improved discrimination power with the ROC increased from 0.79 to 0.94 (p = 0.008). CONCLUSIONS: The enhancement ratio and plaque steepness improved the accuracy over traditional clinical risk factors in predicting recurrent ischemic cerebrovascular events for patients with ICAS. KEY POINTS: • High-resolution magnetic resonance imaging helps clinicians to evaluate high-risk Intracranial plaque. • The higher enhancement ratio and plaque steepness (= height/length) were the primary biomarkers associated with future ischemic cerebrovascular events. • High-resolution magnetic resonance imaging combined with clinical characteristics showed a higher accuracy for the prediction of recurrent events in patients with intracranial atherosclerosis.

Aberrances of Cortex Excitability and Connectivity Underlying Motor Deficit in Acute Stroke.

Purpose: This study was aimed at evaluating the motor cortical excitability and connectivity underlying the neural mechanism of motor deficit in acute stroke by the combination of functional magnetic resonance imaging (fMRI) and electrophysiological measures. Methods: Twenty-five patients with motor deficit after acute ischemic stroke were involved. General linear model and dynamic causal model analyses were applied to fMRI data for detecting motor-related activation and effective connectivity of the motor cortices. Motor cortical excitability was determined as a resting motor threshold (RMT) of motor evoked potential detected by transcranial magnetic stimulation (TMS). fMRI results were correlated with cortical excitability and upper extremity Fugl-Meyer assessment scores, respectively. Results: Greater fMRI activation likelihood and motor cortical excitability in the ipsilesional primary motor area (M1) region were associated with better motor performance. During hand movements, the inhibitory connectivity from the contralesional to the ipsilesional M1 was correlated with the degree of motor impairment. Furthermore, ipsilesional motor cortex excitability was correlated with an enhancement of promoting connectivity in ipsilesional M1 or a reduction of interhemispheric inhibition in contralesional M1. Conclusions: The study suggested that a dysfunction of the ipsilesional M1 and abnormal interhemispheric interactions might underlie the motor disability in acute ischemic stroke. Modifying the excitability of the motor cortex and correcting the abnormal motor network connectivity associated with the motor deficit might be the therapeutic target in early neurorehabilitation for stroke patients.

Emergent loading dose of antiplatelets for stenting after IV rt-PA in acute ischemic stroke: a feasibility study.

BACKGROUND: A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear. METHODS: A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients. RESULTS: A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients. CONCLUSION: Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Simultaneous Multiple Intracerebral Hemorrhages (SMICH).

BACKGROUND AND PURPOSE: Simultaneous multiple intracerebral hemorrhages (SMICHs) are uncommon. Few single-center studies have analyzed characteristics and outcome of SMICH. We analyzed clinical characteristics and outcome of SMICH patients from 2 comprehensive stroke centers. METHODS: Baseline imaging from consecutive intracerebral hemorrhage (ICH) patients (n=1552) from Helsinki ICH study and Royal Melbourne Hospital ICH study was screened for SMICH. ICH pathogenesis was classified according to the structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined classification system (SMASH-U). ICH caused by trauma, tumor, and aneurysmal rupture was excluded. Baseline clinical and radiological characteristics and 90-day mortality were compared between SMICH and single ICH patients. Association of SMICH with 90-day mortality was assessed in multivariable logistic regression models adjusted for predictors of ICH outcome. RESULTS: Of 1452 patients, 85 (5.9%) were classified as SMICH. SMICH were more often female (58% versus 42%; P=0.004), had lower baseline Glasgow Coma Scale (12 versus 14; P=0.008), and more frequent lobar location (59% versus 34%; P<0.001) compared with single ICH. The SMASH-U pathogenesis of SMICH patients was less often hypertensive (20% versus 37%; P=0.001), more often systemic coagulopathy (12% versus 3%; P<0.001), and trended toward more cerebral amyloid angiopathy (32% versus 23%; P=0.071). SMICH was not associated with 90-day mortality on univariate (37% versus 35%; P=0.610), multivariable (odds ratio, 0.783; 95% confidence interval, 0.401-1.529; P=0.473), or propensity score-matched analyses (odds ratio, 0.760; 95% confidence interval, 0.352-1.638; P=0.484). CONCLUSIONS: SMICH occurs in ≈1 in 20 ICH, more commonly with lobar located hematomas and systemic coagulopathy with less hypertensive angiopathy. The associated mortality is similar to single ICH. Given varied etiologies, SMICH management should target the underlying pathology.

Lack of improvement following endovascular therapy in patients with acute ischemic stroke.

BACKGROUND: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months. METHODS: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0-1) or good (grades 2-4). RESULTS: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29-8.19; p = 0.012) and long ORT (OR 3.97, 95% CI: 1.66-9.54; p = 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39-21.61; p < 0.001) was independently associated with unfavorable outcome at 3 months. CONCLUSION: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT.

Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway.

Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 small interfering RNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with Cav-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, phospho-Raf, and phospho-ERK were sequestered in Cav-1 small interfering RNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway is required for the Cav-1's prosurvival role. Together, these findings support Cav-1 as a checkpoint for the in hypoxia-induced astrocyte apoptosis and warrant further studies targeting Cav-1 to treat hypoxic-ischemic brain injury.

Severity assessment of intracranial large artery stenosis by pressure gradient measurements: A feasibility study.

BACKGROUND: Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear. METHODS: Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd /Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded. RESULTS: The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P < 0.01). Only one patient who refused stenting experienced a TIA event in the ipsilateral MCA territory. No recurrent ischemic event was observed in other patients. CONCLUSION: Mean trans-stenotic pressure gradients can be safely and easily measured with a 0.014-inch fluid-filled guide wire in intracranial large arteries. © 2016 Wiley Periodicals, Inc.

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.

Early Magnetic Resonance Imaging Predicts Early Neurological Deterioration in Acute Middle Cerebral Artery Minor Stroke.

BACKGROUND: Early neurological deterioration (END) is an important factor associated with worse clinical outcome in minor strokes. Early magnetic resonance imaging (MRI) findings can provide better sensitivity to delineate stroke pathophysiology and have diagnostic value associated with causative mechanisms. The aim of this study was to investigate the relationship between early MRI finding and the presence of END in minor stroke patients with lesions in the middle cerebral artery (MCA) territory. METHODS: Consecutive MCA minor stroke patients who were admitted to our center within 24 hours of symptom onset were included in this study. All patients underwent MRI within 24 hours of admission. We analyzed baseline characteristics, infarction patterns, and treatment algorithms. The correlation between early MRI findings and END, defined as National Institutes of Health Stroke Scale score increasing more than 2 points during 72 hours after admission, was also determined. RESULTS: Across 211 patients meeting entry criteria between January 2010 and December 2013, internal border-zone (IBZ) infarcts on early MRI scan were observed in 23 of 65 patients with END (35.4%) and in 18 of 146 patients without END (12.3%, P < .001). Patients with IBZ infarcts were found to have more hyperlipidemia, less perforating artery infarcts, more pial artery infarcts, more cortical border-zone infarcts and more ipsilateral large arterial stenosis. Logistic regression analysis revealed that IBZ infarct was independently associated with END after adjustment for other factors (odds ratio, 2.50; 95% confidence interval, 1.09-5.74; P = .031). CONCLUSIONS: Early MRI patterns of IBZ infarction are associated with END in minor stroke patients with acute infarcts of the MCA territory.

An Optical Coherence Tomography Assessment of Stent Strut Apposition Based on the Presence of Lipid-Rich Plaque in the Carotid Artery.

PURPOSE: To evaluate the rate of stent malapposition, plaque prolapse, and fibrous cap rupture detected by optical coherence tomography (OCT) after carotid artery stenting (CAS) based on the presence of lipid-rich plaque, which may be associated with acute stent thrombosis. METHODS: A retrospective study was conducted involving 26 consecutive patients who underwent CAS with OCT imaging acquired before stent deployment and after stent dilation. Adequate imaging quality could not be obtained in 6 patients (out-of-screen images and residual blood), which left 20 patients (mean age 63 years; 13 men) for analysis. Plaque characteristics were determined from 500 selected OCT cross sections; a lipid-rich plaque was defined by lipid present in ≥2 quadrants. Cross-sectional OCT images within the stented segment were evaluated at 1-mm intervals for the presence of malapposition, plaque prolapse, and fibrous cap rupture. The data were compared between patients with and without lipid-rich plaques. The patients were examined at 6 months to determine the degree of in-stent restenosis (ISR). RESULTS: Patients with lipid-rich plaque demonstrated a higher rate of embedded stent struts (29.4% vs 23.7%, p<0.001) and a lower rate of well apposed struts (54.6% vs 59.6%, p<0.001) compared to patients with non-lipid-rich plaque. Rates of plaque prolapse (65.5% vs 49.1%, p<0.001) and fibrous cap rupture (65.5% vs 49.1%, p<0.001) were significantly higher in patients with lipid-rich plaque. ISR ranged from none to 42% in 12 patients; malapposed stent struts and fibrous cap ruptures were not more frequent in the patients with obvious ISR. The 8 patients with no obvious restenosis still had malapposed struts, embedded struts, plaque prolapse, and fibrous cap rupture. CONCLUSION: Embedded stent struts, plaque prolapse, and fibrous cap rupture were more frequent and well-apposed stent struts were less frequent after CAS in patients with lipid-rich plaque.

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.

The Circle of Willis and White Matter Lesions in Patients with Carotid Atherosclerosis.

BACKGROUND: The correlation between cerebral atherosclerosis and white matter lesions (WMLs) in the elderly was controversial in the published articles, where the stenosis was often evaluated by ultrasonography, computed tomography angiography, or magnetic resonance angiography and collaterals were seldom considered. We hypothesized that collaterals influence WMLs. Our study was to explore the relationship between the circle of Willis and WMLs in a retrospective, hospital-based cohort of patients with carotid atherosclerosis. METHODS: Two hundred eighty-six patients with carotid atherosclerosis were enrolled from the Nanjing Stroke Registry. They underwent magnetic resonance imaging evaluating WMLs and digital subtraction angiography evaluating both carotid atherosclerosis and collateral capacity of the circle of Willis. We tested the association between severe carotid atherosclerosis, the circle of Willis, and WMLs by logistic regression analysis. RESULTS: Severity of carotid atherosclerosis was not significantly associated with either periventricular or deep WMLs (P = .656 and .566, respectively). Number of carotid arteries with severe stenosis was not associated with the severity of either periventricular or deep WMLs (P = .721 and .263, respectively). Patency of the communicating arteries (CoA) was not associated with periventricular or deep WMLs (P = .561 and .703, respectively). Advanced age and hypertension were associated with periventricular WMLs (P = .001 and .008, respectively). Advanced age, hypertension, and prior stroke were associated with deep WMLs (P = .049, .048, and .001, respectively). CONCLUSIONS: The circle of Willis and severe carotid atherosclerosis may not be related to WMLs. Further larger studies are warranted to confirm or refute our findings.

Dietary fiber intake reduces risk for gastric cancer: a meta-analysis.

BACKGROUND & AIMS: The association between dietary fiber intake and gastric cancer risk has been investigated by many studies, with inconclusive results. We conducted a meta-analysis of case-control and cohort studies to analyze this association. METHODS: Relevant studies were identified by searching PubMed and Embase through October 2012. We analyzed 21 articles, which included 580,064 subjects. Random-effects models were used to estimate summary relative risks. Dose-response, subgroup, sensitivity, meta-regression, and publication bias analyses were performed. RESULTS: The summary odds ratios of gastric cancer for the highest, compared with the lowest, dietary fiber intake was 0.58 (95% confidence interval, 0.49-0.67) with significant heterogeneity among studies (P < .001, I(2) = 62.2%). Stratified analysis for study design, geographic area, source and type of fiber, Lauren's classification, publication year, sample size, and quality score of study yielded consistent results. Dose-response analysis associated a 10-g/day increment in fiber intake with a significant (44%) reduction in gastric cancer risk. Sensitivity analysis restricted to studies with control for conventional risk factors produced similar results, and omission of any single study had little effect on the combined risk estimate. CONCLUSIONS: In a meta-analysis, we show that dietary fiber intake is associated inversely with gastric cancer risk; the effect probably is independent of conventional risk factors. The direction of the protective association of dietary fiber was consistent among all studies, but the absolute magnitude was less certain because of heterogeneity among the studies. Further studies therefore are required to establish this association.

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.

Forager-farmer transition at the crossroads of East and Southeast Asia 4900 years ago.

The southward expansion of East Asian farmers profoundly influenced the social evolution of Southeast Asia by introducing cereal agriculture. However, the timing and routes of cereal expansion in key regions are unclear due to limited empirical evidence. Here we report macrofossil, microfossil, multiple isotopic (C/N/Sr/O) and paleoproteomic data directly from radiocarbon-dated human samples, which were unearthed from a site in Xingyi in central Yunnan and which date between 7000 and 3300 a BP. Dietary isotopes reveal the earliest arrival of millet ca. 4900 a BP, and greater reliance on plant and animal agriculture was indicated between 3800 and 3300 a BP. The dietary differences between hunter-gatherer and agricultural groups are also evident in the metabolic and immune system proteins analysed from their skeletal remains. The results of paleoproteomic analysis indicate that humans had divergent biological adaptations, with and without farming. The combined application of isotopes, archaeobotanical data and proteomics provides a new approach to documenting dietary and health changes across major subsistence transitions.

Is there a stroke belt in China and why?

BACKGROUND AND PURPOSE: In 1960s, a stroke belt with high stroke mortality was discovered in the southeast United States. In China, where stroke is the leading cause of death, we aimed to determine whether a focal region of high stroke incidence (stroke belt) exits and, if so, the possible causal and modifiable factors. METHODS: We systematically reviewed all studies of stroke incidence in China between 1980 and 2010, and included those which met our criteria for a high-quality study. Criteria for a provincial region of high stroke incidence were ranking in the top one third of all provinces for stroke incidence and ranking of more than one third of prefectural regions within the province in the top two sevenths of all prefectural regions for stroke incidence. We also reviewed regional distribution of major vascular risk factors, socioeconomic status, and demographic profiles in China. RESULTS: Nine eligible studies provided data on the incidence of stroke in 32 of 34 provincial regions of China (with Hong Kong and Macao as exceptions) and 52% of the 347 prefectural regions. Nine provincial regions (Heilongjiang, Tibet, Jilin, Liaoning, Xinjiang, Hebei, Inner Mongolia, Beijing, and Ningxia) met our criteria for a region of high stroke incidence and constitute a stroke belt in north and west China. The incidence of stroke in the stroke belt was 236.2 per 100 000 population compared with 109.7 in regions outside the belt (rate ratio, 2.16; 95% confidence interval, 2.10-2.22). The mean population prevalence of hypertension and overweight (body mass index, >25) was greater in the stroke belt than that in other regions (15.3% versus 10.3%, P<0.001; 21.1% versus 12.3%, P=0.013, respectively). The prevalence of hypertension and overweight also correlated significantly with regional stroke incidence (R=0.642, P<0.001; R=0.438, P=0.014, respectively, by Spearman rank correlation). CONCLUSIONS: A stroke belt of high stroke incidence exists in 9 provincial regions of north and west China. The stroke belt may be caused, at least in part, by a higher population prevalence of hypertension and excess body weight. Lowering blood pressure and body weight in the stroke belt may reduce the geographic disparity in stroke risk and incidence in China.

China interventional stroke registry: rationale and study design.

BACKGROUND: Angioplasty and stenting have recently become attractive options for cerebral large artery stenosis in China. However, there are limited data on safety and long-term outcomes in Chinese patients having undergone cerebral interventional procedures. To address this need, we set up a common database - the China Interventional Stroke Registry (CISR) - to describe patient characteristics, interventional images, periprocedural complications and long-term clinical outcomes and to determine how adherence to guideline-based treatments in the 'real world' works in China. METHODS: Six medical centers have participated since 2004. They entered into an Internet-based database data on demographics, clinical history and angiography of patients undergoing angioplasty with/without stenting in extracranial arteries (carotid, vertebral and subclavian arteries) and/or intracranial arteries (middle cerebral artery, vertebral artery and basilar artery) in China. CISR is a research-funded project. RESULTS: As of October 2012, we have already collected detailed clinical information on 1,356 patients (age: 63.6 ± 10.2 years, male: 1,084, 79.9%). The overall data quality is good. Site data quality control is supported via detailed monthly feedback reports and quarterly data monitoring meetings. CONCLUSIONS: The CISR is the first and the largest registry for angioplasty with/without stents in China. The database will provide the characteristics and outcomes of patients and the situation of adherence to guideline-based treatments under 'real-world' conditions in China.

[Prognostic effect of posterior cerebral artery laterality on middle cerebral artery occlusion].

OBJECTIVE: To explore the prognostic value of posterior cerebral artery (PCA) laterality in patients with symptomatic middle cerebral artery (MCA) occlusion on standard medical therapy. METHODS: Forty consecutive patients with first onset isolated atherosclerotic occlusion in M1 segment of MCA received medication from June 2009 to March 2013. All patients underwent magnetic resonance angiography (MRA) for assessment of PCA laterality. Clinical data and modified Rankin Scale (mRS) at 3 months were compared between PCA positive and negative patients. Retrospective analysis was performed on their clinical and imaging data. RESULTS: Among them, 20 patients (50%) showed PCA laterality on MRA and 32 patients (80%) completed a 3-month follow-up. No significant difference existed between PCA laterality positive and negative groups in a favorable outcome of mRS = 0-1 at 3 months (P = 0.433). CONCLUSION: The presence of PCA laterality showed no prognostic effect on patients with symptomatic MCA occlusion on standard medical therapy.

A clinical prediction model for lung metastasis risk in osteosarcoma: A multicenter retrospective study.

Background: Lung metastases (LM) have a poor prognosis of osteosarcoma. This study aimed to predict the risk of LM using the nomogram in patients with osteosarcoma. Methods: A total of 1100 patients who were diagnosed as osteosarcoma between 2010 and 2019 in the Surveillance, Epidemiology and End Results (SEER) database were selected as the training cohort. Univariate and multivariate logistic regression analyses were used to identify independent prognostic factors of osteosarcoma lung metastases. 108 osteosarcoma patients from a multicentre dataset was as valiation data. The predictive power of the nomogram model was assessed by receiver operating characteristic curves (ROC) and calibration plots, and decision curve analysis (DCA) was utilized to interpret the accurate validity in clinical practice. Results: A total of 1208 patients with osteosarcoma from both the SEER database(n=1100) and the multicentre database (n=108) were analyzed. Univariate and multivariate logistic regression analyses showed that Survival time, Sex, T-stage, N-stage, Surgery, Radiation, and Bone metastases were independent risk factors for lung metastasis. We combined these factors to construct a nomogram for estimating the risk of lung metastasis. Internal and external validation showed significant predictive differences (AUC 0.779, 0.792 respectively). Calibration plots showed good performance of the nomogram model. Conclusions: In this study, a nomogram model for predicting the risk of lung metastases in osteosarcoma patients was constructed and turned out to be accurate and reliable through internal and external validation. Moreover we built a webpage calculator (https://drliwenle.shinyapps.io/OSLM/) taken into account nomogram model to help clinicians make more accurate and personalized predictions.