Nonlinear association of fibrinogen levels with functional prognosis in patients with acute ischemic stroke: a prospective cohort study.

OBJECTIVE: Fibrinogen, essential in primary hemostasis, platelet aggregation, and leukocyte-endothelial interactions, is also associated with a heightened risk of acute ischemic stroke (AIS). However, its influence on AIS patient outcomes is unclear. This study examines the correlation between fibrinogen levels and the risk of unfavorable outcomes three months post-AIS. METHODS: This is a secondary analysis of a prospective cohort study conducted in Korea. The sample consisted of 1851 AIS patients who received treatment at a Korean hospital between January 2010 and December 2016. Statistical models were established to understand the relationship between fibrinogen levels(mg/dL) and unfavorable outcomes(mRs ≥ 3), including logistic regression models, Generalized Additive Models (GAM), and smooth curve fitting (penalized splines). The log-likelihood ratio test has been utilized to evaluate the best fit. To ensure the robustness of the results, sensitivity analyses were conducted by reanalyzing the relationship after excluding participants with TG > 200 mg/dl and BMI > 25 kg/m2. Subgroup analyses were also performed to assess whether influencing factors modify the association between fibrinogen levels and unfavorable outcomes. RESULTS: After adjusting for multiple covariates including age, BMI, sex, LDL-c, TG, HGB, HDL-c, BUN, FPG, ALB, PLT, AF, hypertension, smoking, DM, mRs score at admission, the binary logistic regression model demonstrated revealed a significant positive association between fibrinogen levels and the risk of unfavorable outcomes in AIS patients (OR = 1.215, 95% CI: 1.032-1.429, p = 0.019). Sensitivity analyses supported these findings, with similar ORs observed in subsets of patients with TG < 200 mg/dL (OR = 1.221, 95% CI: 1.036-1.440) and BMI < 25 kg/m2 (OR = 1.259, 95% CI: 1.051-1.509). Additionally, the relationship between fibrinogen levels and outcomes was nonlinear, with a critical threshold of 2.74 g/L. Below the inflection point, the OR for unfavorable outcomes was 0.666 ((95% CI: 0.360, 1.233, p = 0.196), whereas above it, the OR increased to 1.374 (95% CI: 1.138, 1.659). CONCLUSIONS: This study has provided evidence of a positive and nonlinear correlation between fibrinogen levels and 3-month poor functional outcomes in patients with AIS. When fibrinogen levels exceeded 2.74 g/L, a significant and positive association was observed with the risk of poor outcomes. This study provides a further reference for optimizing rehabilitation exercises and facilitating clinical counseling in patients with acute ischemic stroke.

Racial Disparities in Blood Pressure at Time of Acute Ischemic Stroke Presentation: A Population Study.

BACKGROUND: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist. METHODS AND RESULTS: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P<0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P<0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P<0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P<0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P<0.01) were also higher in Black patients. CONCLUSIONS: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.

Individualized antiplatelet therapy for non-cardiogenic ischemic stroke.

OBJECTIVE: This research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. METHODS: Among a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. RESULTS: The individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. CONCLUSION: Individualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.

Trends and predictors of decompressive craniectomy in acute ischemic stroke, 2011-2020.

INTRODUCTION: Rates of decompressive craniectomy (DC) in acute ischemic stroke (AIS) have been reported to decline over time, attributed to an increase in endovascular therapy (EVT) preventing the development of malignant cerebral edema. We sought to characterize trends in DC in AIS between 2011 and 2020. MATERIAL AND METHODS: We performed a retrospective observational study of U.S. AIS hospitalizations using the National Inpatient Sample, 2011 to 2020. We calculated rates of DC per 10,000 AIS among all AIS hospitalizations, as well as AIS hospitalizations undergoing invasive mechanical ventilation (IMV). A logistic regression to determine predictors of DC was performed. RESULTS: Of ∼4.4 million AIS hospitalizations, 0.5 % underwent DC; of ∼300,000 AIS with IMV, 5.8 % underwent DC. From 2011 to 2020, the rate of DC increased from 37.4 to 59.1 per 10,000 AIS (p < 0.001). The rate of DC in patients undergoing IMV remained stable at ∼550 per 10,000 (p = 0.088). The most important factors predicting DC were age (OR 4.88, 95 % CI 4.53-5.25), hospital stroke volume (OR 2.61, 95 % CI 2.17-3.14), hospital teaching status (OR 1.54, 95 % CI 1.36-1.75), and transfer status (OR 1.53, 95 % CI 1.41-1.66); EVT status did not predict DC. CONCLUSIONS: The rate of DC in AIS has increased between 2011 and 2020. Our findings are contrary to prior reports of decreasing DC rates over time. Increasing EVT rates do not seem to be preventing the occurrence of DC. Future research should focus on the decision-making process for both clinicians and surrogates regarding DC with consideration of long-term outcomes.

Stroke incidence increases with diabetic retinopathy severity and macular edema in type 1 diabetes.

BACKGROUND: As the retina is suggested to mirror the brain, we hypothesized that diabetic retinopathy and macular edema are indicative of stroke risk in type 1 diabetes and sought to assess this association in individuals with type 1 diabetes. METHODS: We included 1,268 adult FinnDiane Study participants with type 1 diabetes (age 38.7 ± 11.8 years, 51.7% men vs. 48.3% women, and 31.5% had diabetic kidney disease), data on baseline diabetic retinopathy severity, and first stroke during our observational follow-up. Retinopathy was graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and macular edema as clinically significant (CSME) or not. Strokes identified from registries were confirmed from medical files. Adjusted hazard ratios (HR) for stroke by retinopathy severity and CSME were calculated by Cox models adjusted for clinical confounders, including diabetic kidney disease. RESULTS: During median 18.0 (14.1-19.3) follow-up years, 130 strokes (96 ischemic, 34 hemorrhagic) occurred. With no-very mild (ETDRS 10-20) retinopathy as reference, the adjusted HR for stroke was 1.79 (95%CI 1.02-3.15) in non-proliferative (ETDRS 35-53), and 1.69 (1.02-2.82) in proliferative (ETDRS 61-85) retinopathy. Corresponding adjusted HR for ischemic stroke was 1.68 (0.91-3.10) in non-proliferative and 1.35 (0.77-2.36) in proliferative retinopathy. The adjusted HR for hemorrhagic stroke was 2.84 (0.66-12.28) in non-proliferative and 4.31 (1.16-16.10) in proliferative retinopathy. CSME did not increase HR for any stroke type after adjustment for clinical confounders (data not shown). CONCLUSIONS: Stroke incidence increases with the severity of diabetic retinopathy independently of comorbid conditions, including diabetic kidney disease.

Development and validation of a nomogram for predicting 28-day mortality in patients with ischemic stroke.

BACKGROUND/AIM: We aimed to construct a validated nomogram model for predicting short-term (28-day) ischemic stroke mortality among critically ill populations. MATERIALS AND METHODS: We collected raw data from the Medical Information Mart for Intensive Care IV database, a comprehensive repository renowned for its depth and breadth in critical care information. Subsequently, a rigorous analytical framework was employed, incorporating a 10-fold cross-validation procedure to ensure robustness and reliability. Leveraging advanced statistical methodologies, specifically the least absolute shrinkage and selection operator regression, variables pertinent to 28-day mortality in ischemic stroke were meticulously screened. Next, binary logistic regression was utilized to establish nomogram, then applied concordance index to evaluate discrimination of the prediction models. Predictive performance of the nomogram was assessed by integrated discrimination improvement (IDI) and net reclassification index (NRI). Additionally, we generated calibration curves to assess calibrating ability. Finally, we evaluated the nomogram's net clinical benefit using decision curve analysis (DCA), in comparison with scoring systems clinically applied under common conditions. RESULTS: A total of 2089 individuals were identified and assigned into training (n = 1443) or validation (n = 646) cohorts. Various identified risk factors, including age, ethnicity, marital status, underlying metastatic solid tumor, Charlson comorbidity index, heart rate, Glasgow coma scale, glucose concentrations, white blood cells, sodium concentrations, potassium concentrations, mechanical ventilation, use of heparin and mannitol, were associated with short-term (28-day) mortality in ischemic stroke individuals. A concordance index of 0.834 was obtained in the training dataset, indicating that our nomogram had good discriminating ability. Results of IDI and NRI in both cohorts proved that our nomogram had positive improvement of predictive performance, compared to other scoring systems. The actual and predicted incidence of mortality showed favorable concordance on calibration curves (P > 0.05). DCA curves revealed that, compared with scoring systems clinically used under common conditions, the constructed nomogram yielded a greater net clinical benefit. CONCLUSIONS: Utilizing a comprehensive array of fourteen readily accessible variables, a prognostic nomogram was meticulously formulated and rigorously validated to provide precise prognostication of short-term mortality within the ischemic stroke cohort.

Factors associated with clopidogrel resistance and clinical outcomes in ischemic cerebrovascular disease: A retrospective study.

OBJECTIVE: Clopidogrel resistance may lead to the recurrence of cerebrovascular diseases. We aimed to identify potential factors associated with clopidogrel resistance and evaluate the clinical outcomes of the patients. MATERIALS AND METHODS: In this retrospective study, patients with ischemic cerebrovascular disease treated with clopidogrel were included and classified into 2 groups according to the adenosine diphosphate (ADP)-induced platelet aggregation. Patients with the ADP inhibition rate of <30 % were included in clopidogrel resistance group, otherwise were included in clopidogrel sensitive group. CYP2C19 genotype and other clinical data were analyzed to identify factors and clinical features in the multivariate analysis. The outcomes were vascular events in 6 months. RESULTS: In total, 139 patients were enrolled with 81 (58.27 %) in clopidogrel sensitive group and 58 (41.73 %) in clopidogrel resistance group. Female and CYP2C19 *2*3 carrying were risk factors for clopidogrel resistance, and female was an independent risk factor (OR 2.481, 95 % CI 1.066-5.771, P=0.035). The clopidogrel resistance group showed a higher use rate of argatroban (P=0.030) and a lower arachidonic acid-induced inhibition of platelet aggregation (P=0.036). Clopidogrel resistance was related to the progressing stroke (HR 3.521, 95 % CI 1.352-9.170, P=0.010), but had no influence on the bleeding events (P>0.05). CONCLUSIONS: The risk of clopidogrel resistance increased significantly in female patients. Patients with clopidogrel resistance may have an increased incidence of stroke progression in the acute phase.

Genetically predicted high serum sex hormone-binding globulin levels are associated with lower ischemic stroke risk: A sex-stratified Mendelian randomization study.

OBJECTIVE: Cross-sectional and cohort studies have found insufficient evidence of a causal relationship between sex hormone-binding globulin and ischemic stroke, only associations. Here, we performed a sex-stratified, bidirectional, two-sample Mendelian randomization analysis to evaluate whether a causal relationship exists between sex hormone-binding globulin and ischemic stroke. METHODS: Single-nucleotide polymorphisms associated with sex hormone-binding globulin and ischemic stroke were screened from genome-wide association studies summary data as instrumental variables to enable a bidirectional, two-sample Mendelian randomization study design. Inverse-variance weighted analysis was used as the main method to evaluate potential causality, and additional methods, including the weighted median and MR-Egger tests, were used to validate the Mendelian randomization results. Cochran's Q statistic, MR-Egger intercept test, and Mendelian Randomization-Pleiotropy Residual Sum and Outlier global test were used as sensitivity analysis techniques to assure the reliability of the results. Multivariable analysis was used to show the robustness of the results with key theorized confounders. RESULTS: Inverse-variance weighted analysis showed that genetically predicted higher serum sex hormone-binding globulin levels were associated with significantly decreased risk of ischemic stroke in males (odds radio = 0.934, 95 % confidence interval = 0.885-0.985, P = 0.012) and females (odds radio = 0.924, 95 % confidence interval = 0.868-0.983, P = 0.013). In an analysis of ischemic stroke subtypes, genetically predicted higher serum sex hormone-binding globulin levels were also associated with significantly decreased risk of small-vessel occlusion in both males (odds radio = 0.849, 95 % confidence interval = 0.759-0.949, P = 0.004) and females (odds radio = 0.829, 95 % confidence interval = 0.724-0.949, P = 0.006). The association remained in sensitivity analyses and multivariable analyses. The reverse analysis suggested an association between genetically predicted risk of cardioembolism and increased serum sex hormone-binding globulin in females (Beta = 0.029 nmol/L, Standard Error = 0.010, P = 0.003). CONCLUSION: Our findings provide new insight into the etiology of ischemic stroke and suggest that modulating serum sex hormone-binding globulin may be a therapeutic strategy to protect against ischemic stroke.

The discovery of GGT1 as a novel gene for ischemic stroke conferring protection against disease risk in non-smokers and non-abusers of alcohol.

OBJECTIVES: Increased plasma gamma-glutamyl transferase (GGT1) has been identified as a robust and independent risk factor for ischemic stroke (IS), but the molecular mechanisms of the enzyme-disease association are unclear. The present study investigated whether polymorphisms in the GGT1 gene contribute to IS susceptibility. MATERIALS AND METHODS: DNA samples obtained from 1288 unrelated individuals (600 IS patients and 688 controls) were genotyped for common single nucleotide polymorphisms of GGT1 using the MassArray-4 platform. RESULTS: The rs5751909 polymorphism was significantly associated with decreased risk of ischemic stroke regardless sex and age (Pperm ≤ 0.01, dominant genetic model). The haplotype rs4820599A-rs5760489A-rs5751909A showed strong protection against ischemic stroke (OR 0.53, 95 %CI 0.36 - 0.77, Pperm ≤ 0.0001). The protective effect of SNP rs5751909 in the stroke phenotype was successfully replicated in the UK Biobank, SiGN, and ISGC cohorts (P ≤ 0.01). GGT1 polymorphisms showed joint (epistatic) effects on the risk of ischemic stroke, with some known IS-associated GWAS loci (e.g., rs4322086 and rs12646447) investigated in our population. In addition, SNP rs5751909 was found to be strongly associated with a decreased risk of ischemic stroke in non-smokers (OR 0.54 95 %CI 0.39-0.75, Pperm = 0.0002) and non-alcohol abusers (OR 0.43 95 %CI 0.30-0.61, Pperm = 2.0 × 10-6), whereas no protective effects of this SNP against disease risk were observed in smokers and alcohol abusers (Pperm < 0.05). CONCLUSIONS: We propose mechanisms underlying the observed associations between GGT1 polymorphisms and ischemic stroke risk. This pilot study is the first to demonstrate that GGT1 is a novel susceptibility gene for ischemic stroke and provides additional evidence of the genetic contribution to impaired redox homeostasis underlying disease pathogenesis.

Development and Validation of Machine Learning Algorithms to Predict 1-Year Ischemic Stroke and Bleeding Events in Patients with Atrial Fibrillation and Cancer.

In this study, we leveraged machine learning (ML) approach to develop and validate new assessment tools for predicting stroke and bleeding among patients with atrial fibrillation (AFib) and cancer. We conducted a retrospective cohort study including patients who were newly diagnosed with AFib with a record of cancer from the 2012-2018 Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The ML algorithms were developed and validated separately for each outcome by fitting elastic net, random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), and neural network models with tenfold cross-validation (train:test = 7:3). We obtained area under the curve (AUC), sensitivity, specificity, and F2 score as performance metrics. Model calibration was assessed using Brier score. In sensitivity analysis, we resampled data using Synthetic Minority Oversampling Technique (SMOTE). Among 18,388 patients with AFib and cancer, 523 (2.84%) had ischemic stroke and 221 (1.20%) had major bleeding within one year after AFib diagnosis. In prediction of ischemic stroke, RF significantly outperformed other ML models [AUC (0.916, 95% CI 0.887-0.945), sensitivity 0.868, specificity 0.801, F2 score 0.375, Brier score = 0.035]. However, the performance of ML algorithms in prediction of major bleeding was low with highest AUC achieved by RF (0.623, 95% CI 0.554-0.692). RF models performed better than CHA2DS2-VASc and HAS-BLED scores. SMOTE did not improve the performance of the ML algorithms. Our study demonstrated a promising application of ML in stroke prediction among patients with AFib and cancer. This tool may be leveraged in assisting clinicians to identify patients at high risk of stroke and optimize treatment decisions.

Ischemic stroke as an initial performance of polycythemia vera in young adults: A case report and literature review.

INTRODUCTION: As the second leading cause of death and disability worldwide, stroke is mainly caused by atherosclerosis and cardiac embolism, particularly in older individuals. Nevertheless, in young and otherwise healthy individuals, the causes of stroke can be more diverse and may include conditions such as patent foramen ovale, vasculitis, coagulopathies, genetic factors, or other undetermined causes. Although these other causes of stroke account for a relatively small proportion compared to ischemic stroke, they are becoming increasingly common in clinical practice and deserve attention. Here, we present a rare female patient with polycythemia vera (PV) who was admitted to the hospital as a stroke patient without any previous medical history. PATIENT CONCERNS: A 40-year-old young woman felt sudden dizziness and slow response. After 4 days of being admitted, she developed blurry vision on the right. DIAGNOSES: Cranial magnetic resonance imaging revealed aberrant signals in the left temporal and parietal lobe, as well as multiple small focal signal abnormalities were observed in the left frontal lobe. Magnetic resonance angiography revealed partial stenosis of the left internal carotid artery. The patient's blood routine examination revealed a significant elevation in complete blood counts, particularly the increase in red blood cells, as well as prolonged clotting time. An abdominal ultrasound and abdomen computed tomography showed splenomegaly. The outcome of the genetic testing was positive for the Janus kinase JAK2 exon V617F mutation (JAK2/V617F). The patient was diagnosed with PV-related stroke. INTERVENTIONS: The patient was treated with phlebotomy, cytoreductive therapy, and low-dose aspirin antiplatelet therapy and was regularly followed up in hematology and neurology clinics after discharge. OUTCOMES: The patient's red blood cell, leukocyte, and thrombocyte counts had fully normalized, with her hemoglobin level measuring at 146 g/L and hematocrit value at 43%. Furthermore, there had been a significant improvement in neurological symptoms. LESSONS: PV, a rare hematological disorder, can present with ischemic stroke as the initial performance, and the diagnosis mainly relies on routine blood tests, bone marrow biopsies, and genetic test. Therefore, clinicians should pay attention to PV, a low-prevalence disease, when encountering stroke in youth.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

Expression, Functional Polymorphism, and Diagnostic Values of MIAT rs2331291 and H19 rs217727 Long Non-Coding RNAs in Cerebral Ischemic Stroke Egyptian Patients.

Cerebral ischemic stroke (CIS) is a severe cerebral vascular event. This research aimed to evaluate the role of single-nucleotide polymorphisms (SNPs) of the lncRNAs MIAT rs2331291 and H19 rs217727 and epigenetic methylation in the expression patterns of serum lncRNA H19 in CIS Egyptian patients. It included 80 CIS cases and 40 healthy subjects. Serum MIAT expression levels decreased, whereas serum H19 expression levels increased among CIS compared to controls. For MIAT rs2331291, there were significant differences in the genotypic and allelic frequencies between the CIS and healthy subjects at p = 0.02 and p = 0.0001, respectively. Our findings illustrated a significantly increased MIAT T/T genotype frequency in hypertensive CIS compared to non-hypertensive CIS at p = 0.004. However, H19 rs217727 gene frequency C/C was not significantly higher in non-hypertensive CIS than in hypertensive CIS. The methylation of the H19 gene promoter was significantly higher in CIS patients compared to healthy subjects. The level of MIAT was positively correlated with serum H19 in CIS. Receiver operating characteristics (ROC) analysis revealed that serum MIAT and H19 have a high diagnostic potential for distinguishing CIS subjects from healthy ones. In conclusion, the MIAT-rs2331291 polymorphism might serve as a novel potential indicator of CIS.

Liver fibrosis index is associated with functional outcome among acute ischemic stroke patients.

INTRODUCTION: The fibrosis-4 (FIB-4) index and the fibrosis-5 (FIB-5) index are noninvasive markers of liver fibrosis in patients with nonalcoholic fatty liver disease. Although liver fibrosis a potential risk factor for stroke development, it is uncertain whether liver fibrosis influences stroke outcomes. We investigated the associations between these two indices and stroke patient outcomes and compared their predictive accuracy. METHODS: We conducted a double-center, hospital-based, retrospective study. Consecutive acute ischemic stroke patients (n=2399) were analyzed. We calculated the FIB-4 index and the FIB-5 index and evaluated their relationships with poor stroke outcome, which was defined as a modified Rankin Scale score of 3-6 at three months after stroke. We evaluated the ability of each index to predict stroke outcome according to cutoff values calculated from receiver operating characteristic (ROC) curves. RESULTS: Of 2399 recruited patients, 1549 patients (mean age, 73 years) were analyzed. The FIB-4 index and FIB-5 index had similar areas under their ROC curves for predicting stroke outcome (FIB-4 index, 0.675 and FIB-5 index, 0.683, P=0.334). The cutoff points of the FIB-4 index and FIB-5 index according to the ROC analysis were associated with poor stroke outcome in the multivariable analyses (odds ratio [OR] 2.23, 95 % confidence interval [CI] 1.72-2.89, OR 1.93, 95 % CI 1.47-2.54, respectively). CONCLUSIONS: Liver fibrosis scores may be useful for predicting outcomes in patients with acute stroke. The FIB-4 and FIB-5 indices should be considered comprehensive tools for assessing the outcome risk after ischemic stroke.

A case-control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics.

BACKGROUND: Past studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted. RESULTS: The mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance. CONCLUSIONS: This study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance.

Relationship between the cumulative exposure to atherogenic index of plasma and ischemic stroke: a retrospective cohort study.

BACKGROUND: Atherogenic index of plasma (AIP) has been demonstrated as a surrogate marker for ischemic stroke, but there is limited evidence for the effect of long-term elevation of AIP on ischemic stroke. Therefore, we aimed to characterize the relationship between cumulative exposure to AIP and the risk of ischemic stroke. METHODS: A total of 54,123 participants in the Kailuan Study who attended consecutive health examinations in 2006, 2008, and 2010 and had no history of ischemic stroke or cancer were included. The time-weighted cumulative AIP (cumAIP) was calculated as a weighted sum of the mean AIP values for each time interval and then normalized to the total duration of exposure (2006-2010). Participants were divided into four groups according to quartile of cumAIP: the Q1 group, ≤-0.50; Q2 group, - 0.50 to - 0.12; Q3 group, - 0.12 to 0.28; and Q4 group, ≥ 0.28. Cox proportional hazard models were used to evaluate the relationship between cumAIP and ischemic stroke by calculating hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: After a median follow-up of 11.03 years, a total of 2,742 new ischemic stroke events occurred. The risk of ischemic stroke increased with increasing quartile of cumAIP. After adjustment for potential confounders, Cox regression models showed that participants in the Q2, Q3, and Q4 groups had significantly higher risks of ischemic stroke than those in the Q1 group. The HRs (95% CIs) for ischemic stroke in the Q2, Q3, and Q4 groups were 1.17 (1.03, 1.32), 1.33 (1.18, 1.50), and 1.45 (1.28, 1.64), respectively. The longer duration of high AIP exposure was significantly associated with increased ischemic stroke risk. CONCLUSIONS: High cumulative AIP is associated with a higher risk of ischemic stroke, which implies that the long-term monitoring and maintenance of an appropriate AIP may help prevent such events.

Prognostic utility of MicroRNA-221 and interleukin-6 in cerebral ischemic stroke.

Cerebral ischemic stroke has a significant mortality rate and persistent impairment. The initial diagnosis of stroke occurs by magnetic resonance imaging and computed tomography. There is a strong need for more accessible, less expensive, and non-invasive methods besides the neuroimaging methods. MicroRNAs (miRNAs) are critical regulators for ischemic stroke as they are involved in stroke pathophysiology. The goal of the current study was to determine whether microRNA-221 (miR-221) could be used as a diagnostic biomarker for patients with ischemic stroke, and whether it can serve as a promising indicator of the disease severity especially if combined with interleukin-6 (IL-6). The study included 90 subjects, 45 cerebral ischemic stroke patients and 45 controls. MiR-221 was evaluated by quantitative real-time polymerase chain reaction (q-PCR) and IL-6 by enzyme-linked immunosorbent assay (ELISA). Our study results revealed that the serum miR-221 level was significantly reduced in cerebral ischemic stroke patients when compared to the control group (p<0.0001). In addition, serum miR-221 showed a significant negative correlation with cerebral stroke severity (p<0.0001), whereas serum IL-6 showed a significant positive correlation with cerebral stroke severity (p < 0.0001). We also analyzed the receiver operator characteristic (ROC) curve and found that area under the ROC curve (AUC) for severity of ischemic stroke by miR-221 was 0.97 (95% confidence intervall0.93-1, p<0.001). Notably, the combination of serum miR-221 with IL-6 for prediction of ischemic stroke severity showed both increased sensitivity/specificity (AUC=0.99, 95% confidence interval 0.96-1, p<0.001) than miR-221 alone. We concluded that miR-221 constituted a non-invasive, sensitive, and specific biomarker that could be used for diagnosis of ischemic stroke and for prediction of its severity.

Use of biomarkers for predicting a malignant course in acute ischemic stroke: an observational case-control study.

Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers-S100B protein, MMP-9, and IL-10-were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke.

Prognostic Nutritional Index (PNI) as a potential predictor and intervention target for perioperative ischemic stroke: a retrospective cohort study.

BACKGROUND: The prognostic nutritional index (PNI) is a nutritional indicator and predictor of various diseases. However it is unclear whether PNI can be a predictor of perioperative ischemic stroke. This study aims to evaluate the association of the preoperative PNI and ischemic stroke in patients undergoing non-cardiac surgery. METHODS: The retrospective cohort study included patients who underwent noncardiac surgery between January 2008 and August 2019. The patients were divided into PNI ≥ 38.8 and PNI < 38.8 groups according to the cut-off value of PNI. Univariate and multivariate logistic regression analyses were performed to explore the association between PNI and perioperative ischemic stroke. Subsequently, propensity score matching (PSM) analysis was performed to eliminate the confounding factors of covariates and further validate the results. Subgroup analyses were completed to assess the predictive utility of PNI for perioperative ischemic stroke in different groups. RESULTS: Amongst 221,542 hospitalized patients enrolled, 485 (0.22%) experienced an ischemic stroke within 30 days of the surgery, 22.1% of patients were malnourished according to PNI < 38.8, and the occurrence of perioperative ischemic stroke was 0.34% (169/49055) in the PNI < 38.8 group. PNI < 38.8 was significantly associated with an increased incidence of perioperative ischemic stroke whether in univariate logistic regression analysis (OR = 1.884, 95% CI: 1.559-2.267, P < 0.001) or multivariate logistic regression analysis (OR = 1.306, 95% CI: 1.061-1.602, P = 0.011). After PSM analysis, the ORs of PNI < 38.8 group were 1.250 (95% CI: 1.000-1.556, P = 0.050) and 1.357 (95% CI: 1.077-1.704, P = 0.009) in univariate logistic regression analysis and multivariate logistic regression analysis respectively. The subgroup analysis indicated that reduced PNI was significantly associated to an increased risk of perioperative ischemic stroke in patients over 65 years old, ASA II, not taking aspirin before surgery, without a history of stroke, who had neurosurgery, non-emergency surgery, and were admitted to ICU after surgery. CONCLUSIONS: Our study indicates that low preoperative PNI is significantly associated with a higher incidence of ischemic stroke in patients undergoing non-cardiac surgery. Preoperative PNI, as a preoperative nutritional status evaluation index, is an independent risk factor useful to predict perioperative ischemic stroke risk, which could be used as an intervenable preoperative clinical biochemical index to reduce the incidence of perioperative ischemic stroke.

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.