Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

AIM: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. METHODS: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

Trends of Sex Differences and Associated Factors in Stroke Outcomes Among Patients With Acute Ischemic Stroke: 2007 to 2018

BACKGROUND AND OBJECTIVES: Female patients have been shown to experience worse clinical outcomes after acute ischemic stroke (AIS) compared with male patients. We aimed to estimate the temporal trends in the sex differences in stroke outcomes and identify risk factors contributing to the sex differences spanning 10 years in China. METHODS: This cohort study was conducted based on data from the China National Stroke Registries (CNSRs, comprising 3 phases, I-III, from 2007 to 2018). Patients with ischemic stroke within 7 days of symptom onset were included. The primary outcome was a 12-month poor functional outcome. Other outcomes included mortality and disability-adjusted life-year (DALY) lost. The sex differences in outcomes and associated factors were estimated using multivariable logistic regression. The sex differences between CNSRs were tested by the interaction of sex and time. RESULTS: Among 42,564 patients included, 35.4% were female. The age-adjusted event rate of 12-month poor functional outcome and mortality decreased both in male and female patients after stroke onset (CNSRs I, II, and III, all p varies over time <0.001). There was a decrease in DALY lost for both sexes over the decade (male patients: from 10.1 to 9.3 DALYs; female patients: from 10.9 to 9.6 DALYs). Female patients showed worse 12-month poor functional outcome in CNSRs I and II (odds ratio [OR] with 95% CI: 1.24 [1.10-1.39] and 1.12 [1.01-1.25], respectively) compared with male patients, but the sex difference attenuated in CNSR III (OR with 95% CI: 1.02 [0.89-1.16]), with the temporal trend (p varies over time = 0.004). The sex difference and the temporal trend of the sex difference in mortality from 2007 to 2018 were not found (p varies over time = 0.45). The most important factors attenuating the sex difference in poor functional outcome in CNSRs I and III were education level, socioeconomic deprivation, baseline stroke severity, and current smoking. DISCUSSION: This study demonstrated that the sex disparity in poor functional outcome at 12 months was substantially narrowed covering 10 years and completely attenuated in 2015-2018. The findings suggested that female patients have experienced larger improvements in stroke outcomes than male patients over the past decade.

Predictors of dysphagia screening and pneumonia among patients with intracerebral haemorrhage in China: a cross-sectional hospital-based retrospective study.

OBJECTIVES: This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH). DESIGN: Our study was a cross-sectional hospital-based retrospective study. STUDY DESIGN AND SETTINGS: We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia. PARTICIPANTS: We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were DS and pneumonia during acute hospitalisation. RESULTS: In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9-13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95). CONCLUSION: Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes.

Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies. METHODS: We prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2-6] at 3 months. RESULTS: Of the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0-69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00-5.98, p = 0.049, pinteraction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12-0.76, p = 0.01, pinteraction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02-0.42, p = 0.002; pinteraction = 0.001). CONCLUSION: CHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients.

Revisiting the Smoking Paradox in Acute Ischemic Stroke Patients: Findings From the Chinese Stroke Center Alliance Study.

Background Smoking is a well-established risk factor for the development of acute ischemic stroke (AIS). However, the "smoker's paradox" suggests that it is associated with favorable clinical outcomes following stroke. We aimed to reevaluate the association between smoking and in-hospital outcomes in patients with AIS in contemporary practice. Methods and Results A total of 649 610 inpatients with AIS from 1476 participating hospitals in the Chinese Stroke Center Alliance were included. In-hospital outcomes measurement included all-cause mortality, discharge against medical advice, and complications. Multivariable logistic regression models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital management were used to evaluate the association between smoking and in-hospital outcomes. A propensity score-matched analysis was also conducted. Of these patients with AIS, 36.8% (n=238 912) were smokers. Smokers were younger, had fewer comorbidities, and had slightly lower rates of adverse in-hospital outcomes than nonsmokers (all-cause death or discharge against medical advice: 6.0% versus 6.1%; in-hospital complications: 14.5% versus 15.1%). Multivariable analysis revealed that smoking was associated with higher risk of adverse in-hospital outcomes (all-cause death or discharge against medical advice: odds ratio [OR], 1.05 [95% CI, 1.02-1.08]; P<0.001; complications: OR, 1.06 [95% CI, 1.04-1.08]; P<0.001). The excess risk of adverse in-hospital outcomes remained in smoking patients with AIS after propensity score-matching analysis (all-cause death or discharge against medical advice: OR, 1.04 [95% CI, 1.00-1.08]; P=0.034; complications: OR, 1.05 [95% CI, 1.03-1.08]; P<0.001). Conclusions Smoking was associated with increased risk of adverse in-hospital outcomes among patients with AIS in contemporary practice, reinforcing the importance of smoking cessation in patients with AIS.

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay.

Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome analysis on ischemic stroke by deeply sequencing and analyzing 10,241 stroke patients from China. We identified 135.59 million variants, > 42% of which were novel. Notable disparities in allele frequency were observed between Chinese and other populations for 89 variants associated with stroke risk and 10 variants linked to response to stroke medications. We investigated the population structure of the participants, generating a map of genetic selection consisting of 31 adaptive signals. The adaption of the MTHFR rs1801133-G allele, which links to genetically evaluated VB9 (folate acid) in southern Chinese patients, suggests a gene-specific folate supplement strategy. Through genome-wide association analysis of 18 stroke-related traits, we discovered 10 novel genetic-phenotypic associations and extensive cross-trait pleiotropy at 6 lipid-trait loci of therapeutic relevance. Additionally, we found that the set of loss-of-function and cysteine-altering variants present in the causal gene NOTCH3 for the autosomal dominant stroke disorder CADASIL displayed a broad neuro-imaging spectrum. These findings deepen our understanding of the relationship between the population and individual genetic layout and clinical phenotype among stroke patients, and provide a foundation for future efforts to utilize human genetic knowledge to investigate mechanisms underlying ischemic stroke outcomes, discover novel therapeutic targets, and advance precision medicine.

Mediation effect of stroke recurrence in the association between post-stroke interleukin-6 and functional disability.

AIM: Post-stroke inflammation increases the risk of functional disability through enlarged cerebral infarct size directly and follow-up stroke event indirectly. We aimed to use post-stroke proinflammatory cytokine interleukin-6 (IL-6) as a marker of inflammatory burden and quantify post-stroke inflammation's direct and indirect effect on functional disability. METHODS: We analyzed patients with acute ischemic stroke admitted to 169 hospitals in the Third China National Stroke Registry. Blood samples were collected within 24 h of admission. Stroke recurrence and functional outcome measured by the modified Rankin scale (mRS) were assessed via face-to-face interviews at 3 months. Functional disability was defined as an mRS score ≥2. Mediation analyses under the counterfactual framework were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between IL-6 and functional outcome. RESULTS: Among the 7053 analyzed patients, the median (interquartile range [IQR]) NIHSS score was 3 (1-5), and the median (IQR) level of IL-6 was 2.61 (1.60-4.73) pg/mL. Stroke recurrence was observed in 458 (6.5%) patients, and functional disability was seen in 1708 (24.2%) patients at the 90-day follow-up. Per stand deviation (4.26 pg/mL) increase in the concentration of IL-6 was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.19; 95% CI, 1.09-1.29) and disability (aOR, 1.22; 95% CI, 1.15-1.30) within 90 days. Mediation analyses revealed that 18.72% (95% CI, 9.26%-28.18%) of the relationship between IL-6 and functional disability was mediated by stroke recurrence. CONCLUSIONS: Stroke recurrence mediates less than 20% of the association between IL-6 and functional outcome at 90 days among patients with acute ischemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes directly.

Development of a minimally invasive surgical guide template for flapless extraction of deeply impacted premolars: A technical note and case report.

The emergence of digital surgical guide templates in alveolar surgery has rapidly increased in the past decade, coinciding with the advancements in 3D printing technology. In contrast to conventional freehand procedures, the utilization of digital templates serves as a 'bridge' that facilitates the extraction of impacted teeth with expedited and accurate intraoperative localization, resulting in a notable reduction in surgical duration, minimized trauma, and lowered risk. However, there is significant scope for enhancements in surgical techniques and refinement of surgical guide templates. The purpose of our study was to employ an innovative surgical guide template founded on computer-aided design for the purpose of executing flapless extraction of deeply impacted teeth and investigating a surgical approach that is more effective, secure, and less invasive.

Association Between CYP2B6 Polymorphisms and Efficacy of Clopidogrel in Minor Stroke or Transient Ischemic Attack.

BACKGROUND: CYP2B6 (cytochrome P450 subfamily IIB polypeptide 6), encoded by the CYP2B6 gene, is a critical enzyme involved in clopidogrel metabolism. However, the association between CYP2B6 polymorphisms and the efficacy of clopidogrel in minor stroke or transient ischemic attack for secondary stroke prevention remains unclear. METHODS: Based on CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) randomized clinical trial of aspirin plus clopidogrel versus aspirin alone, we investigated the role of CYP2B6 polymorphisms and the efficacy of clopidogrel in patients with minor stroke or transient ischemic attack in China from October 2009 to July 2012. A total of 2853 patients were successfully genotyped for CYP2B6-516G>T, rs3745274 and CYP2B6-1456 T>C, rs2054675. The primary efficacy and safety outcomes were new stroke and any bleeding within 90 days. RESULTS: Among the 2853 patients, 32.8% were identified as the carriers of the CYP2B6-516 GT/TT or -1456 TC/CC genotype. The incidences of 90-day new stroke in aspirin plus clopidogrel and aspirin alone groups were 7.1% versus 11.3% among noncarriers, respectively; and 9.7% versus 12.2% among carriers, respectively. The efficacy of aspirin plus clopidogrel versus aspirin alone was not significantly different (P interaction=0.29) in noncarriers (adjusted hazard ratio, 0.61 [95% CI, 0.45-0.83]) compared to carriers (adjusted hazard ratio, 0.80 [95% CI, 0.54-1.18]). The incidence (n=51) of 90-day any bleeding in aspirin plus clopidogrel and aspirin alone groups were 2.2% (21 bleeds) versus 1.9% (18 bleeds) among noncarriers (adjusted hazard ratio, 1.11 [95% CI, 0.59-2.09]) and 1.9% (9 bleeds) versus 0.7% (3 bleeds) among carriers (adjusted hazard ratio, 3.23 [95% CI, 0.86-12.12]). Similar findings were observed during the 1-year follow-up. CONCLUSIONS: In this post hoc analysis of the CHANCE trial, we did not observe a significant difference in the efficacy of aspirin plus clopidogrel compared with aspirin in carriers versus noncarriers of CYP2B6-516 GT/TT or -1456 TC/CC genotype. Our results suggest that both carriers and noncarriers suffering from a minor stroke are likely to benefit from aspirin plus clopidogrel treatment over aspirin monotherapy for secondary prevention. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00979589.

Ticagrelor Aspirin vs Clopidogrel Aspirin in CYP2C19 Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile.

BACKGROUND AND OBJECTIVE: Genotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel aspirin depended on CYP2C19 genotype and risk profile. A stratification of patients who carried CYP2C19 loss-of-function (LOF) alleles according to the risk of recurrent stroke may be important for selecting optimal antiplatelet therapy. We aimed to compare the efficacy and safety of ticagrelor aspirin with clopidogrel aspirin in CYP2C19 LOF carriers with minor stroke or transient ischemic attack (TIA) stratified by risk profile. METHODS: Data were obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low-risk and high-risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively). RESULTS: A total of 6,412 CYP2C19 LOF carriers were enrolled; ticagrelor aspirin was associated with a reduced risk of primary outcome (new stroke within 90-day follow-up) in patients at low risk (hazard ratio [HR], 0.65; 95% CI, 0.48-0.82), but not in those at high risk (HR, 0.97; 95% CI, 0.73-1.29), compared with clopidogrel aspirin (p = 0.02 for interaction). Secondary outcomes generally went in the same direction as the primary outcome. The primary safety outcome of severe or moderate bleeding did not differ based on risk profile (p = 0.24 for interaction), although the incidence of total bleeding was greater with ticagrelor aspirin than with clopidogrel aspirin among patients at low risk (p < 0.01 for interaction). Analysis in the per-protocol population yielded similar results. DISCUSSION: This post hoc analysis of CHANCE-2 trial showed that CYP2C19 LOF carriers with minor stroke or TIA at low risk of recurrent stroke received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CYP2C19 LOF carriers with minor stroke or TIA at low risk, but not at high risk, of recurrent stroke (by the ESRS) received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. TRIAL REGISTRATION INFORMATION: URL: www. CLINICALTRIALS: gov. Unique identifier: NCT04078737.

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 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 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.

A case of ischemic stroke with hemorrhagic transformation associated with essential thrombocythemia and JAK-2 V617F mutation.

BACKGROUND: Essential thrombocythemia (ET) is a rare cause of stroke. The V617F mutation in the Janus kinase 2 (JAK2) gene is one of the most typical mutations in ET and has been shown to be a risk factor for stroke, especially in younger people. However, to date, there have been few reports of intracranial thrombotic and hemorrhagic complications in patients with ET. Herein, we present a case of JAK2 gene mutation-associated ET in a patient who developed both ischemic and hemorrhagic stroke, and discuss potential underlying mechanisms. CASE PRESENTATION: A 45-year-old Chinese male presented to our center with gradually developing weakness of the right limbs for 3 months. A computed tomography scan of the brain showed an area of infarction with hemorrhage in the left subcortical and corona radiata regions. High-resolution magnetic resonance imaging revealed a thrombosis on the surface of the atherosclerotic plaque. Digital subtraction angiography revealed an insect bite-like change in the C1 branch of the left internal carotid artery, which caused up to 50% stenosis. Blood tests showed continued elevation of the platelet and white blood cell counts. After consultation with a hematologist, a bone marrow biopsy was performed, which revealed proliferative bone marrow changes with numerous megakaryocytes and proliferative but mature granulocytes. Further genetic testing revealed a positive JAK2-V617F mutation. Therefore, the diagnosis of ET was confirmed according to the World Health Organization (WHO) 2016 diagnostic criteria. Finally, we decided to administer aspirin and hydroxyurea. The patient remained stroke free and the platelet levels were normal throughout the 1-year follow-up period. CONCLUSIONS: JAK2 mutations affect the proliferation and differentiation of blood cells through the JAK, signal transducer and activator of transcription pathway, which leads to changes in platelets and macrophages, and an increase in neutrophil extracellular traps, which may explain the patient's ischemic and hemorrhagic changes. Further investigation of the underlying mechanisms may change the treatment strategy for such patients in the future.

Pre-stroke dementia and in-hospital outcomes in the Chinese Stroke Center Alliance.

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia. Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated. Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83). Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia.

Evaluation of Diffusion-Perfusion Mismatch in Acute Ischemic Stroke with a New Automated Perfusion-Weighted Imaging Software: A Retrospective Study.

INTRODUCTION: The aim of this study was to evaluate the accuracy of automated software (iStroke) on magnetic resonance (MR) apparent diffusion coefficient (ADC) and perfusion-weighted imaging (PWI) against ground truth in assessing infarct core, and compare the hypoperfusion volume and mismatch volume on iStroke with those on Food and Drug Administration-approved software (RAPID) in patients with acute ischemic stroke. METHODS: We used the single-volume decomposition method to develop the iStroke (iStroke; Beijing Tiantan Hospital, Beijing, China) software. Patients with ischemic stroke were collected from two educational hospitals in China with MR-PWI performed in the emergency department within 24 h of symptom onset. Infarct core volume was defined as ADC < 620 × 10-6 mm2/s and hypoperfusion volume was defined as Tmax > 6 s. We compared the accuracy of infarct core volume using iStroke and RAPID (iSchema View Inc, Menlo Park, CA) software with ground truth. RESULTS: We included 405 patients with acute ischemic stroke with MR ADC and PWI sequences. The infarct core volume on iStroke (median 2.43 ml, interquartile range [IQR] 0.60-10.32 ml) was not significantly different from the ground truth (median 2.89 ml, IQR 0.77-9.17 ml) (P = 0.07); Bland-Altman curves showed that the core volume of iStroke and RAPID software were comparable with each other on individual agreement with ground truth. The hypoperfusion volume and mismatch volume on iStroke were not statistically different from those on the RAPID software, respectively. In patients with large vessel occlusion (n = 74), the agreement between iStroke and RAPID was substantial (kappa = 0.76) according to DEFUSE 3 criteria (infarct core < 70 ml, mismatch volume ≥ 15 ml, and mismatch ratio ≥ 1.8). CONCLUSIONS: The iStroke automatic processing of ADC and PWI is a reliable software for the identification of diffusion-perfusion mismatch in acute ischemic stroke.

Data-driven clustering approach to identify novel phenotypes using multiple biomarkers in acute ischaemic stroke: A retrospective, multicentre cohort study.

Background: Acute ischaemic stroke (AIS) is a highly heterogeneous disorder and warrants further investigation to stratify patients with different outcomes and treatment responses. Using a large-scale stroke registry cohort, we applied data-driven approach to identify novel phenotypes based on multiple biomarkers. Methods: In a nationwide, prospective, 201-hospital registry study taking place in China between August 01, 2015 and March 31, 2018, the patients with AIS who were over 18 years of age and admitted to the hospital within 7 days from symptom onset were included. 92 biomarkers were included in the analysis. In the derivation cohort (n=9539), an unsupervised Gaussian mixture model was applied to categorize patients into distinct phenotypes. A classifier was developed using the most important biomarkers and was applied to categorize patients into their corresponding phenotypes in an validation cohort (n=2496). The differences in biological features, clinical outcomes, and treatment response were compared across the phenotypes. Findings: We identified four phenotypes with distinct characteristics in 9288 patients with non-cardioembolic ischaemic stroke. Phenotype 1 was associated with abnormal glucose and lipid metabolism. Phenotype 2 was characterized by inflammation and abnormal renal function. Phenotype 3 had the least laboratory abnormalities and small infarct lesions. Phenotype 4 was characterized by disturbance in homocysteine metabolism. Findings were replicated in the validation cohort. In comparison with phenotype 3, the risk of stroke recurrence (adjusted hazard ratio [aHR] 2.02, 95% confidence intervals [CI] 1.04-3.94), and mortality (aHR 18.14, 95%CI 6.62-49.71) at 3-month post-stroke were highest in phenotype 2, followed by phenotype 4 and phenotype 1, after adjustment for age, gender, smoking, drinking, history of stroke, hypertension, diabetes mellitus, dyslipidemia, and coronary heart disease. The Monte Carlo simulation showed that the patients with phenotype 2 could benefit from high-intensity statin therapy. Interpretation: A data-driven approach could aid in the identification of patients at a higher risk of adverse clinical outcomes following non-cardioembolic ischaemic stroke. These phenotypes, based on different pathophysiology, can suggest individualized treatment plans. Funding: Beijing Natural Science Foundation (grant number Z200016), Beijing Municipal Committee of Science and Technology (grant number Z201100005620010), National Natural Science Foundation of China (grant number 82101360, 92046016, 82171270), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant number 2019-I2M-5-029).

Trends and Risk Factors Associated With Stroke Recurrence in China, 2007-2018.

Importance: Recurrent stroke rates have decreased substantially in Western countries. However, data on changes in stroke recurrence and risk factor patterns in China are limited. Objective: To systematically assess stroke recurrence trends by evaluating temporal improvement in guideline-recommended secondary prevention treatment performance and changes in risk factor patterns over 10 years in China. Design, Setting, and Participants: This post hoc cohort study was conducted based on data from the China National Stroke Registries (CNSRs, comprising 3 phases, I-III, from 2007-2018). Participants were patients with ischemic stroke who were enrolled in CNSR I or III within 7 days of symptom onset. Data were analyzed from September through November 2021. Exposures: Vascular risk factors included current smoking, alcohol consumption, hypertension, diabetes, coronary artery disease, atrial fibrillation, and low-density lipoprotein cholesterol (LDL-C) levels. Main Outcomes and Measures: The cumulative incidence rates of stroke recurrence at 3, 6, and 12 months were calculated, and the performance of guideline-based secondary prevention treatments was investigated at each visit in CNSR I (2007-2008) and III (2015-2018). Logistic regression models were used to evaluate changes in risk factor patterns for stroke recurrence based on data from CNSR I and III. Results: A total of 10 952 patients with ischemic stroke from CNSR I (6740 [61.5%] men; median [IQR] age, 67 [57-75] years) and 10 348 patients with ischemic stroke from CNSR III (7128 [68.9%] men; median [IQR] age, 63 [54-70] years) were selected. Over 10 years, the adjusted cumulative incidence of recurrent stroke within 12 months decreased from 15.5% (95% CI, 14.8%-16.2%) to 12.5% (95% CI, 11.9%-13.1%) (P < .001). Factors associated with increased risk of stroke in CNSR I that were still associated after 10 years included age per 10 years (CNSR I: odds ratio [OR], 1.24; 95% CI, 1.18-1.31; CNSR III: OR, 1.08; 95% CI, 1.01-1.15), prior stroke (CNSR I: OR, 1.62; 95% CI, 1.45-1.82; CNSR III: OR, 1.66; 95% CI, 1.44-1.92), coronary heart disease (CNSR I: OR, 1.21; 95% CI, 1.04-1.40; CNSR III: OR, 1.23; 95% CI, 1.02-1.49), and LDL-C level per 10 mg/dL (0.259 mmol/L) (CNSR I: OR, 1.02; 95% CI, 1.01-1.04; CNSR III: OR, 1.02; 95% CI, 1.00-1.03), whereas atrial fibrillation (CNSR I: OR, 1.51; 95% CI, 1.26-1.81; CNSR III: OR, 0.95; 95% CI, 0.74-1.23) was no longer an independent risk factor in 2015 to 2018. Conclusions and Relevance: This study found that stroke recurrence rate in China decreased significantly, but approximately 12.5% of patients still experienced stroke recurrence within 12 months. These findings suggest that more intensive control of traditional risk factors, including LDL-C levels, may be needed to further reduce stroke recurrence.

ICH-LR2S2: a new risk score for predicting stroke-associated pneumonia from spontaneous intracerebral hemorrhage.

PURPOSE: We develop a new risk score to predict patients with stroke-associated pneumonia (SAP) who have an acute intracranial hemorrhage (ICH). METHOD: We applied logistic regression to develop a new risk score called ICH-LR2S2. It was derived from examining a dataset of 70,540 ICH patients between 2015 and 2018 from the Chinese Stroke Center Alliance (CSCA). During the training of ICH-LR2S2, patients were randomly divided into two groups - 80% for the training set and 20% for model validation. A prospective test set was developed using 12,523 patients recruited in 2019. To further verify its effectiveness, we tested ICH-LR2S2 on an external dataset of 24,860 patients from the China National Stroke Registration Management System II (CNSR II). The performance of ICH-LR2S2 was measured by the area under the receiver operating characteristic curve (AUROC). RESULTS: The incidence of SAP in the dataset was 25.52%. A 24-point ICH-LR2S2 was developed from independent predictors, including age, modified Rankin Scale, fasting blood glucose, National Institutes of Health Stroke Scale admission score, Glasgow Coma Scale score, C-reactive protein, dysphagia, Chronic Obstructive Pulmonary Disease, and current smoking. The results showed that ICH-LR2S2 achieved an AUC = 0.749 [95% CI 0.739-0.759], which outperforms the best baseline ICH-APS (AUC = 0.704) [95% CI 0.694-0.714]. Compared with the previous ICH risk scores, ICH-LR2S2 incorporates fasting blood glucose and C-reactive protein, improving its discriminative ability. Machine learning methods such as XGboost (AUC = 0.772) [95% CI 0.762-0.782] can further improve our prediction performance. It also performed well when further validated by the external independent cohort of patients (n = 24,860), ICH-LR2S2 AUC = 0.784 [95% CI 0.774-0.794]. CONCLUSION: ICH-LR2S2 accurately distinguishes SAP patients based on easily available clinical features. It can help identify high-risk patients in the early stages of diseases.

The Contribution of Inflammation to Stroke Recurrence Attenuates at Low LDL-C Levels.

AIMS: Residual inflammation risk refers to inflammation that still increases the risk of cardiovascular disease after the level of low-density lipoprotein cholesterol (LDL-C) reached the target (＜70 mg/dL). However, whether inflammation is still an important issue even if very low LDL-C levels have been achieved remains unclear. This study aimed to investigate the contribution of inflammation to stroke recurrence on different LDL-C levels following ischemic stroke (IS) or transient ischemic attack (TIA). METHODS: A total of 10499 IS/TIA patients whose LDL-C and high-sensitivity C-reactive protein (hsCRP) were measured were selected from the Third China National Stroke Registry. The cutoff values were set to 25, 35, 45, 55, 70, and 100 mg/dL for LDL-C, whereas the threshold values of hsCRP and interleukin-6 (IL-6) were 2 mg/L and 1.65 ng/L, respectively. Based on each group of LDL-C, Cox regressions were conducted to investigate the associations between inflammation and recurrent stroke within 1 year. RESULTS: The associations between baseline hsCRP levels and stroke recurrence were non-significant in groups with LDL-C ＜55 mg/dL (P＞0.05). After stratification by baseline LDL-C of 55 mg/dL, hsCRP ≥ 2 mg/L (10.9% versus 7.5%, P＜0.0001) and IL-6 ≥ 1.65 ng/L (9.8% versus 7.4%, P=0.0002) were found to be related to a high incidence of recurrent IS among patients with LDL-C ≥ 55 mg/dL; however, no associations were observed among patients with LDL-C ＜55 mg/dL. Compared with low inflammation (both hsCRP ＜2 mg/L and IL-6 ＜1.65 ng/L), high inflammation (both hsCRP ≥ 2 mg/L and IL-6 ≥ 1.65 ng/L) was significantly associated with stroke recurrence when LDL-C ≥ 55 mg/dL (adjusted HR 1.38, 95% CI 1.10-1.74), whereas this association was not observed when LDL-C ＜55 mg/dL (adjusted HR, 0.72; 95% CI, 0.41-1.25). CONCLUSION: For IS/TIA patients, the contribution of inflammation to stroke recurrence seems to be attenuated at a low level of LDL-C.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Bleeding Risk of Dual Antiplatelet Therapy after Minor Stroke or Transient Ischemic Attack.

OBJECTIVE: This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack. METHODS: A total of 6,412 patients were enrolled from the CHANCE-2 (Clopidogrel with Aspirin in High-Risk Patients with Acute Non-disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries). RESULTS: A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor-aspirin compared with clopidogrel-aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68-2.89, p < 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52-0.95, p = 0.02). Additionally, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with higher risk of bleeding in patients aged <65 years (HR = 2.87, 95% CI = 1.95-4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88-3.73; p for interaction = 0.04 and 0.03, respectively). INTERPRETATION: Bleeding events mostly occurred within the 21-day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor-aspirin compared with clopidogrel-aspirin, particularly in patients aged <65 years and nondiabetic patients. ANN NEUROL 2022;91:380-388.