Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke:a prospective cohort study

Background Somatic mutation contributes to clonal haematopoiesis of indeterminate potential(CHIP)is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease.Here,we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke(AIS)cohort and explored the underlying mechanisms.Methods We studied a prospective cohort of 6016 patients who had a first-ever AIS in China.Whole-genome sequencing was performed to identify CHIP.High-sensitivity C reactive protein(hs-CRP)levels above 3 mg/L at baseline were defined as hyperinflammation.Recurrent stroke during the 3-month follow-up was the primary outcome.Results Among the 6016 patients who had a first-ever AIS,with a median age was 62 years(IQR,54.0‒70.0),3.70%were identified as CHIP carriers.The most common mutations occurred in the DNMT3A(30.0%)and TET2(11.4%)genes.During a follow-up of 3 months,the presence of CHIP was associated with recurrent stroke(HR 1.62,95%CI 1.04 to 2.51,p=0.03),recurrent ischaemic stroke(HR 1.64,95%CI 1.04 to 2.58,p=0.03)and combined vascular events(HR 1.58,95%CI 1.02 to 2.44,p=0.04)after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS.Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation(OR 3.10,95%CI 1.92 to 5.00,p<0.001)but not in those without hyperinflammation(OR 0.18,95%CI 0.03 to 1.04,p=0.06,Pinteraction=0.002).Conclusion Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS.Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.

缺血性卒中后感染介导了低密度脂蛋白胆固醇与全因死亡风险之间的U形曲线关系

在缺血性卒中急性期,尚不清楚低水平的低密度脂蛋白胆固醇(LDL-C)的病理生理意义,本研究旨在评估LDL-C水平、卒中后感染和全因死亡间的关系.研究共纳入804,855名缺血性卒中患者.通过多元logistic回归模型分析LDL-C水平、感染和死亡之间的关系,采用基于反事实框架的中介分析,以阐明卒中后感染的中介效应,研究发现LDL-C与死亡风险之间呈U形曲线关系,死亡风险最低的LDL-C水平为2.67mmol/L.经多因素校正后,与LDL-C=2.50~2.99mmol/L相比,LDL-C<1.0mmol/L患者的死亡风险比值比(OR)为2.22(95%置信区间(CI):1.77~2.79),LDL-C5.0mmol/L患者的OR为1.22(95%CI:0.98~1.50).LDL-C与死亡之间关联的38.20%(95%CI:5.96~70.45,P=0.020)由感染介导:在逐步剔除存在心血管危险因素的患者后,LDL-C与全因死亡间的U形曲线关系及感染的中介效应与主要分析一致,而死亡风险最低时的LDL-C水平逐渐升高.在缺血性卒中急性期,LDL-C水平与全因死亡之间存在U形曲线关系,其被卒中后感染介导。

Temporal trends and rural-urban disparities in cerebrovascular risk factors,in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015:a nationwide serial cross-sectional survey

Background Stroke is the leading cause of mortality in China,with limited evidence of in-hospital burden obtained from nationwide surveys.We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors,management and outcomes from 2005 to 2015.Methods We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005,2010 and 2015.We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach.We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.Results We analysed 28277 ischaemic stroke admissions from 189 participating hospitals.From 2005 to 2015,the estimated national hospital admission rate for ischaemic stroke per 100000 people increased(from 75.9 to 402.7,Ptrend<0.001),and the prevalence of risk factors,including hypertension,diabetes,dyslipidaemia and current smoking,increased.The composite score of diagnostic tests for stroke aetiology assessment(from 0.22 to 0.36,Ptrend<0.001)and secondary prevention treatments(from 0.46 to 0.70,Ptrend<0.001)were improved.A temporal decrease was found in discharge against medical advice(DAMA)(from 15.2%(95%CI 13.7%to 16.7%)to 8.6%(8.1%to 9.0%);adjusted Ptrend=0.046),and decreases in in-hospital mortality(0.7%in 2015 vs 1.8%in 2005;adjusted OR(aOR)0.52;95%CI 0.32 to 0.85)and the composite outcome of in-hospital mortality or DAMA(8.4%in 2015 vs 13.9%in 2005;aOR 0.65;95%CI 0.47 to 0.89)were observed.Disparities between rural and urban hospitals narrowed;however,disparities persisted in in-hospital management(brain MRI:rural-urban difference from−14.4%to−11.2%;cerebrovascular assessment:from−20.3%to−16.7%;clopidogrel:from−2.1%to−10.3%;anticoagulant for atrial fibrillation:from−10.9%to−8.2%)and in-hospital outcomes(DAMA:from 2.7%to 5.0%;composite outcome of in-hospital mortality or DAMA:from 2.4%to 4.6%).Conclusions From 2005 to 2015,improvements in hospital admission and in-hospital management for ischaemic stroke in China were found.A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed.Disparities between rural and urban hospitals generally narrowed but persisted.

Development and Validation of a Prognostic Model for One-year Survival of Cirrhosis Patients with First-ever Spontaneous Bacterial Peritonitis

Background and Aims: Spontaneous bacterial peritonitis(SBP) is one of the leading causes of death in patients withliver cirrhosis. We aimed to establish a prognostic model toevaluate the 1-year survival of cirrhosis patients after thefirst episode of SBP. Methods: A prognostic model was developedbased on a retrospective derivation cohort of 309cirrhosis patients with first-ever SBP and was validated in aseparate validation cohort of 141 patients. We used Uno’sconcordance, calibration curve, and decision curve (DCA)analysis to evaluate the discrimination, calibration, and clinicalnet benefit of the model. Results: A total of 59 (19.1%)patients in the derivation cohort and 42 (29.8%) patientsin the validation cohort died over the course of 1 year. Aprognostic model in nomogram form was developed withpredictors including age [hazard ratio (HR): 1.25;95% confidenceinterval (CI): 0.92–1.71], total serum bilirubin (HR:1.66;95% CI: 1.28–2.14), serum sodium (HR: 0.94;95%CI: 0.90–0.98), history of hypertension (HR: 2.52;95% CI:1.44–4.41) and hepatic encephalopathy (HR: 2.06;95%CI: 1.13–3.73). The nomogram had a higher concordance(0.79) compared with the model end-stage liver disease(0.67) or Child-Turcotte-Pugh (0.71) score. The nomogramalso showed acceptable calibration (calibration slope, 1.12;Bier score, 0.15±0.21) and optimal clinical net benefit in thevalidation cohort. Conclusions: This prediction model developedbased on characteristics of first-ever SBP patientsmay benefit the prediction of patients’ 1-year survival.

Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism(SPACE)trial:rationale and design

Backgrounds Embolic stroke is one of the main mechanisms of ischaemic stroke.Even if treated with recommended antithrombotic agents,stroke recurrence remains high.The Shuxuetong injection,a purified extract of traditional Chinese medicine widely used for thrombus diseases in clinical practice in China,could be a promising agent to prevent stroke recurrence.Aims To describe the design of the Shuxuetong injection for prevention of recurrence in acute ischaemic stroke with embolism mechanisms.Design The Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism(SPACE)trial is a multicentre,randomised,double-blind,placebo-controlled,parallel-group,superiority trial to evaluate the efficacy and safety of Shuxuetong injection in reducing recurrence or silent new ischaemic lesions on patients with acute embolic stroke within 10 days.An estimated 2416 patients with embolic stroke within 72 hours of symptom onset from 80 hospitals will be randomly assigned to one of two groups receiving Shuxuetong injection or placebo injection for 10 days.The primary endpoint is symptomatic or asymptomatic new cerebral infarction within 10 days after randomisation.Conclusion The SPACE Trial will provide valuable evidence for the efficacy and safety of Shuxuetong injection for the prevention of stroke recurrence in patients with imaging-defined embolic stroke.

China Stroke Statistics 2019:A Report From the National Center for Healthcare Quality Management in Neurological Diseases,China National Clinical Research Center for Neurological Diseases,the Chinese Stroke Association,National Center for Chronic and Non-communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations

China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading causes of death behind malignant tumours and heart disease.The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100000 population and 246.8 per 100000 person-years,respectively.According to the Global Burden of Disease Study 2017,the years of life lost(YLLs)per 100000 population for stroke increased by 14.6%;YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.The absolute numbers and rates per 100000 population for all-age disability-adjusted life years(DALYs)for stroke increased substantially between 1990 and 2017,and stroke was the leading cause of all-age DALYs in 2017.The main contributors to cerebrovascular diseases include behavioural risk factors(smoking and alcohol use)and pre-existing conditions(hypertension,diabetes mellitus,dyslipidaemia and atrial fibrillation(AF)).The most prevalent risk factors among stroke survivors were hypertension(63.0%-84.2%)and smoking(31.7%-47.6%).The least prevalent was AF(2.7%-7.4%).The prevalences for major risk factors for stroke are high and most have increased over time.Based on the latest national epidemiological data,26.6%of adults aged≥15 years(307.6 million adults)smoked tobacco products.For those aged≥18 years,age-adjusted prevalence of hypertension was 25.2%;adjusted prevalence of hypercholesterolaemia was 5.8%;and the standardised prevalence of diabetes was 10.9%.For those aged≥40 years,the standardised prevalence of AF was 2.31%.Data from the Hospital Quality Monitoring System showed that 3010204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.Of those,2466785(81.9%)were ischaemic strokes(ISs);447609(14.9%)were intracerebral haemorrhages(ICHs);and 95810(3.2%)were subarachnoid haemorrhages(SAHs).The average age of patients admitted was 66 years old,and nearly 60%were male.A total of 1555(0.1%),2774(0.6%)and 1347(1.4%)paediatric strokes(age<18 years)were identified among IS,ICH and SAH,respectively.Over one-third(1063892(35.3%))of the patients were covered by urban resident basic medical insurance,followed by urban employee basic medical insurance(699513(23.2%))and new rural cooperative medical schema(489361(16.3%)).The leading risk factor was hypertension(67.4%for IS,77.2%for ICH and 49.1%for SAH),and the leading comorbidity was pneumonia or pulmonary infection(10.1%for IS,31.4%for ICH and 25.2%for SAH).In-hospital death/discharge against medical advice rate was 8.3%for stroke inpatients,ranging from 5.8%for IS to 19.5%for ICH.The median and IQR of length of stay was 10.0(7.0-14.0)days,ranging from 10.0(7.0-13.0)in IS to 14.0(8.0-22.0)in SAH.Data from the Chinese Stroke Center Alliance demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS,ICH and SAH were 0.77±0.21,0.72±0.28 and 0.59±0.32,respectively.