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Hu L, Qiao Z, Xu M, Feng J, Shan Q, Sheng X, Xu G, Xu Y, Hu W, Wang G, Jin X. Establishment and validation of a 3-month prediction model for poor functional outcomes in patients with acute cardiogenic cerebral embolism related to non-valvular atrial fibrillation. Front Neurol 2024; 15:1392568. [PMID: 38841691 PMCID: PMC11150815 DOI: 10.3389/fneur.2024.1392568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 05/09/2024] [Indexed: 06/07/2024] Open
Abstract
Objectives Cardiogenic cerebral embolism (CCE) poses a significant health risk; however, there is a dearth of published prognostic prediction models addressing this issue. Our objective is to establish prognostic prediction models (PM) for predicting poor functional outcomes at 3 months in patients with acute CCE associated with non-valvular atrial fibrillation (NVAF) and perform both internal and external validations. Methods We included a total of 730 CCE patients in the development cohort. The external regional validation cohort comprised 118 patients, while the external time-sequential validation cohort included 63 patients. Multiple imputation by chained equations (MICE) was utilized to address missing values and the least absolute shrink and selection operator (LASSO) regression was implemented through the glmnet package, to screen variables. Results The 3-month prediction model for poor functional outcomes, denoted as N-ABCD2, was established using the following variables: NIHSS score at admission (N), Age (A), Brain natriuretic peptide (BNP), C-reactive protein (CRP), D-dimer polymers (D), and discharge with antithrombotic medication (D). The model's Akaike information criterion (AIC) was 637.98, and the area under Curve (AUC) for the development cohort, external regional, and time-sequential cohorts were 0.878 (95% CI, 0.854-0.902), 0.918 (95% CI, 0.857-0.979), and 0.839 (95% CI, 0.744-0.934), respectively. Conclusion The N-ABCD2 model can accurately predict poor outcomes at 3 months for CCE patients with NVAF, demonstrating strong prediction abilities. Moreover, the model relies on objective variables that are readily obtainable in clinical practice, enhancing its convenience and applicability in clinical settings.
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Affiliation(s)
- Lan Hu
- Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Zhenguo Qiao
- Department of Gastroenterology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Mengshi Xu
- Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Jie Feng
- Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Qingting Shan
- Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Xihua Sheng
- Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Guoli Xu
- Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Yuan Xu
- Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Wenze Hu
- Department of Nursing, Ezhou Polytechnic, Ezhou, Hubei, China
| | - Guojun Wang
- Department of Neurology, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People’s Hospital, Suzhou, Jiangsu, China
| | - Xuehong Jin
- Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
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Hao Z, Wei J, Li X, Wei W, Pan Y, Chen C, Zhu H, Xiang X, Ma A, Xin W. Inflammation-associated D-dimer predicts neurological outcome of recent small subcortical infarct: A prospective clinical and laboratory study. Clin Neurol Neurosurg 2024; 237:108126. [PMID: 38290168 DOI: 10.1016/j.clineuro.2024.108126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/14/2024] [Accepted: 01/17/2024] [Indexed: 02/01/2024]
Abstract
OBJECTIVE Elevated level of D-Dimer often indicates a worse prognosis in cerebral infarction. However, there is limited research on this impact within recent small subcortical infarction (RSSI). We aim to explore the role of inflammation and the total magnetic resonance imaging (MRI) burden of cerebral small vessel disease (cSVD) in this process. METHODS 384 RSSI patients and 189 matched healthy controls were strictly registered in the current research. We evaluated short-term and long-term outcomes by measuring the percentage of the National Institutes of Health Stroke Scale (NIHSS) improvement and the modified Rankin Scale (mRS) at 3 months, respectively. We also assessed the chronic, sustained brain damage associated with cSVD using the total MRI burden and confirmed the relationship between prognosis and the total MRI burden of cSVD. Furthermore, we explored the associations between D-dimer and C-reactive protein (CRP) levels with NIHSS improvement and mRS at 3 months, as well as their relationships with both the total MRI burden of cSVD and its 4 imaging features. RESULTS Both NIHSS improvement and the mRS at 3 months were found to be correlated with the total MRI burden of cSVD. Higher D-dimer and CRP levels showed a linear correlation, indicating worse prognosis and a higher total MRI burden of cSVD. The four imaging features of the total MRI burden of cSVD did not exhibit entirely consistent patterns when exploring their correlations with prognosis and laboratory indicators. CONCLUSION Inflammation-associated D-dimer predicts neurological outcomes in patients with recent small subcortical infarct, and reflects a more severe total MRI burden of cSVD.
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Affiliation(s)
- Zhongnan Hao
- Department of Neurosurgery, First Affiliated Hospital of Nanchang University, Nanchang 330209, China; Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Jin Wei
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Xuening Li
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Wei Wei
- Department of Neurology, the Affiliated Hospital of Southwest Jiaotong University & The Third People's Hospital of Chengdu, Chengdu, Sichuan 610000, China
| | - Yongli Pan
- Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Chuanfu Chen
- Department of Neurosurgery, First Affiliated Hospital of Nanchang University, Nanchang 330209, China
| | - Hongji Zhu
- Department of Neurosurgery, First Affiliated Hospital of Nanchang University, Nanchang 330209, China
| | - Xiaofeng Xiang
- Department of Neurosurgery, First Affiliated Hospital of Nanchang University, Nanchang 330209, China
| | - Aijun Ma
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
| | - Wenqiang Xin
- Department of Neurosurgery, First Affiliated Hospital of Nanchang University, Nanchang 330209, China.
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Wen H, Wang N, Hou R. Correlation analysis between D-dimer-to-fibrinogen-ratio and carotid plaque in young patients aged 18-45 with acute cerebral infarction. Clin Neurol Neurosurg 2022; 222:107427. [PMID: 36108464 DOI: 10.1016/j.clineuro.2022.107427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 09/02/2022] [Accepted: 09/03/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND D-Dimer and fibrinogen were commonly used to detect the coagulation and fibrinolytic function, but D-dimer to fibrinogen ratio (DFR) in carotid plaque in young patients aged 18-45 with acute cerebral infarction (ACI) has not been used clinically. In this work, we focused on the evaluation of the DFR value of this group of patients and analyzed its possible correlation. METHODS A total of 164 patients with ACI patients aged 18-45 were selected as research subjects after their first admission. They had undergone carotid plaque contrast-enhanced ultrasound (CEUS) and were divided into two groups with carotid plaque (n = 97) and with no carotid plaque (n = 67). According to NIHSS score and carotid plaque grade, the clinical symptoms of patients were judged. Univariate and multivariate analyses were conducted to compare the risk factors of carotid plaque in ACI patients. RESULTS The DFR value of patients in the carotid plaque group (103.41 ± 20.81) was significantly higher than that of the no carotid plaque control group (88.9 ± 26.51). We also identified DFR X103 was the only independent risk factor (β = 0.53; 95% CI, 0.914-0.984; P = 0.05). DFR X103 was increased with the severity of the disorder and with the CEUS grades. The area under the DFR curve was 0.673 (95% CI 0.584～0.762). CONCLUSION The value of the DFR is positively correlated with CEUS carotid plaque grading and NIHSS score, which can predict the severity of carotid plaque in ACI patients aged 18-45. Therefore it is worthy of clinical application.
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Affiliation(s)
- Huijun Wen
- Department of Neurology, Baoji Municipal Central Hospital, Baoji, Shaanxi 721008, PR China
| | - Ning Wang
- Department of Neurology, Baoji Municipal Central Hospital, Baoji, Shaanxi 721008, PR China
| | - Ruihua Hou
- Department of Neurology, Baoji Municipal Central Hospital, Baoji, Shaanxi 721008, PR China.
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Yang X, Lu T, Qu Z, Zhang Y, Liu P, Ma Y. Plasma D-dimer level is associated with clinical outcomes in patients with atrial fibrillation related acute ischemic stroke after pneumonia. BMC Neurol 2021; 21:137. [PMID: 33773590 PMCID: PMC8004437 DOI: 10.1186/s12883-021-02168-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 03/23/2021] [Indexed: 12/11/2022] Open
Abstract
Background Pneumonia is related to poor prognosis in acute ischemic stroke (AIS), and its risk might be higher in atrial fibrillation (AF) related AIS with elevated plasma D-dimer. The aim of our study was to investigate the prognostic value of D-dimer for predicting clinical outcome of AF-related AIS with pneumonia. Method AF-related AIS patients with pneumonia were prospectively enrolled. Receiver operating characteristic (ROC) curve was used to determine the optimal D-dimer point for 3-month mortality and death/severe disability. The associations between the D-dimer and 3-month mortality and death/severe disability were assessed by multivariable logistic regression analysis. Results A total of 415 patients were enrolled in this study. ROC curve analysis showed that the optimal cut point of D-dimer for 3-month death/severe disability and mortality were D-dimer≥2.35 mg/l and D-dimer≥3.35 mg/l, respectively. Multivariable logistic regression analysis showed that D-dimer≥2.35 mg/l [adjusted odds ratio (aOR) 5.99, 95% confidence interval (CI): 3.04–11.83, P<0.001], higher NIHISS score (aOR:1.53, 95% CI: 1.38–1.69, P<0.001) and larger infarct volume (aOR 1.01, 95% CI: 1.01–1.02, P<0.001) were associated with increased risk of 3-month death/severe disability), and anticoagulant was associated with decreased risk of death/severe disability (aOR:0.21, 95% CI: 0.09–0.47, P<0.001). Higher NIHISS score (aOR:1.64, 95% CI: 1.38–1.94, P<0.001), older age (aOR 1.08, 95% CI: 1.02–1.14, P = 0.007), D-dimer≥3.35 mg/l (OR 8.49, 95% CI: 4.13–17.84,P<0.001), larger infarct volume (aOR 1.02, 95% CI: 1.00–1.03, P = 0.014), and higher CRUB-65 score (aOR 6.43, 95% CI: 3.10–13.34, P<0.001) were associated with increased risk of 3-month mortality. Conclusions AF-related AIS patients with concurrent high D-dimer and pneumonia increased risk of 3-month mortality and death/severe disability, plasma D-dimer may have predictive value in outcome after AF-related AIS with pneumonia.
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Affiliation(s)
- Xu Yang
- Department of Neurology, Nanchong Central Hospital; The Second Clinical Medical School, North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
| | - Taoli Lu
- Department of Neurology, Chengdu second people's hospital, Chengdu, 610015, Sichuan, China
| | - Zhanli Qu
- Department of Neurology, Nanchong Central Hospital; The Second Clinical Medical School, North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Yi Zhang
- Department of Neurology, Nanchong Central Hospital; The Second Clinical Medical School, North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Pingping Liu
- Department of Neurology, Nanchong Central Hospital; The Second Clinical Medical School, North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Ying Ma
- Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
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Hou H, Xiang X, Pan Y, Li H, Meng X, Wang Y. Association of Level and Increase in D-Dimer With All-Cause Death and Poor Functional Outcome After Ischemic Stroke or Transient Ischemic Attack. J Am Heart Assoc 2021; 10:e018600. [PMID: 33412918 PMCID: PMC7955415 DOI: 10.1161/jaha.120.018600] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Background D‐dimer is involved in poor outcomes of stroke as a coagulation biomarker. We aimed to investigate the associations of the level and increase in D‐dimer between baseline and 90 days with all‐cause death or poor functional outcome in patients after ischemic stroke or transient ischemic attack. Methods and Results We collected data from the CNSRIII (Third China National Stroke Registry) study. The present substudy included 10 518 patients within 7 days (baseline) of ischemic stroke or transient ischemic attack and 6268 patients at 90 days. Poor functional outcome at 1 year was assessed on the basis of the modified Rankin Scale (≥3). Multivariable Cox regression or logistic regression was used to assess the association of D‐dimer levels with all‐cause death or poor functional outcome. D‐dimer levels at 90 days were lower than those at baseline (1.4 µg/mL versus 1.7 µg/mL; P<0.001). Higher baseline D‐dimer level was associated with all‐cause death (adjusted hazard ratio [HR], 1.77; 95% CI, 1.25–2.52; P=0.001) and poor functional outcome (adjusted odds ratio [OR], 1.49; 95% CI, 1.23–1.80; P<0.001) during 1‐year follow‐up. Higher D‐dimer level at 90 days was also associated with poor outcomes independently. Furthermore, an increase in D‐dimer levels between baseline and 90 days was associated with all‐cause death (since 90 days to 1 year after index event) (adjusted HR, 1.99; 95% CI, 1.12–3.53; P=0.019) but not with poor functional outcome (adjusted OR, 1.08; 95% CI, 0.82–1.41). Conclusions Our study shows that high level and an increase in D‐dimer between baseline and 90 days are associated with poor outcomes in patients after ischemic stroke or transient ischemic attack.
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Affiliation(s)
- Huiqing Hou
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.,China National Clinical Research Center for Neurological Diseases Beijing China.,Center of Stroke Beijing Institute for Brain Disorders China.,Department of Neurology the Second Hospital of Hebei Medical University Shijiazhuang China
| | - Xianglong Xiang
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.,China National Clinical Research Center for Neurological Diseases Beijing China.,Center of Stroke Beijing Institute for Brain Disorders China
| | - Yuesong Pan
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.,China National Clinical Research Center for Neurological Diseases Beijing China.,Center of Stroke Beijing Institute for Brain Disorders China
| | - Hao Li
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.,China National Clinical Research Center for Neurological Diseases Beijing China.,Center of Stroke Beijing Institute for Brain Disorders China
| | - Xia Meng
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.,China National Clinical Research Center for Neurological Diseases Beijing China.,Center of Stroke Beijing Institute for Brain Disorders China
| | - Yongjun Wang
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.,China National Clinical Research Center for Neurological Diseases Beijing China.,Center of Stroke Beijing Institute for Brain Disorders China
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Abbas NI, Sayed O, Samir S, Abeed N. D-dimer Level is Correlated with Prognosis, Infarct Size, and NIHSS in Acute Ischemic Stroke Patients . Indian J Crit Care Med 2021;25:193-198. [PMID: 33707899 PMCID: PMC7922437 DOI: 10.5005/jp-journals-10071-23744] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Stroke ranks the fourth leading disease causing adult mortality and disability. D-dimer (D-D) is the ultimate product of plasmin-mediated degradation of fibrin-rich thrombi. D-D is a simple readily accessible biomarker employed within the diagnostic algorithms for the exclusion of venous thromboembolism. The correlation between D-D infarct size in MRI brain, APACHE II score, and the National Institute of Health Stroke Scale (NIHSS) score in critically ill acute stroke patients has not been fully investigated before. Objective We aimed to investigate the diagnostic and prognostic value of elevated plasma D-D in critically ill patients admitted with acute cerebrovascular accidents. As far as we know, we are the first to investigate the correlation between plasma D-D levels and the ischemic lesion size in MRI brain and also APACHE II score and NIHSS in critically ill acute ischemic cerebrovascular patients. Setting and participants A prospective, observational cohort study inside the Critical Care Medicine Department. Thirty patients with AIS were enrolled additionally to 1 healthy age- and sex-matched controls. Interventions We employed particle-enhanced, immunoturbidimetric assay to detect plasma D-D concentrations. D-D levels D0 and D1 were measured upon admission and 24 hours later, respectively. We reviewed the patient' s health records; additionally, demographic, clinical, laboratory, and neuroimaging information was abstracted. Results D-D concentrations were significantly higher in acute stroke patients compared to healthy controls. ROC curve analysis showed that elevated D-D level more than 310 ng/mL can predict infarct lesion size >1.5 cm in diffusion-weighted MRI brain with sensitivity and specificity (100 and 83%, respectively) and also admission D-D (D0) at cutoff concentration 350 ng/mL and D1 at cutoff value 370 ng/mL are predictors of complicated course with sensitivity and specificity (100 and 84.6%, respectively). There was no significant difference between D0 and D1 D-D levels (p-value >0.05). Conclusion The plasma D-D biomarker can be a simple readily available test reliable predictor of infarct lesion size >1.5 cm in DW-MRI and outcome in union with the common practice instrumental tests. How to cite this article Abbas NI, Sayed O, Samir S, Abeed N. D-dimer Level is Correlated with Prognosis, Infarct Size, and NIHSS in Acute Ischemic Stroke Patients. Indian J Crit Care Med 2021;25(2):193-198.
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Affiliation(s)
- Nora I Abbas
- Critical Care Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Osama Sayed
- Critical Care Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sherif Samir
- Critical Care Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nashwa Abeed
- Critical Care Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Harpaz D, Seet RCS, Marks RS, Tok AIY. Blood-Based Biomarkers Are Associated with Different Ischemic Stroke Mechanisms and Enable Rapid Classification between Cardioembolic and Atherosclerosis Etiologies. Diagnostics (Basel) 2020; 10:E804. [PMID: 33050269 PMCID: PMC7600601 DOI: 10.3390/diagnostics10100804] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 09/29/2020] [Accepted: 10/07/2020] [Indexed: 12/22/2022] Open
Abstract
Stroke is a top leading cause of death, which occurs due to interference in the blood flow of the brain. Ischemic stroke (blockage) accounts for most cases (87%) and is further subtyped into cardioembolic, atherosclerosis, lacunar, other causes, and cryptogenic strokes. The main value of subtyping ischemic stroke patients is for a better therapeutic decision-making process. The current classification methods are complex and time-consuming (hours to days). Specific blood-based biomarker measurements have promising potential to improve ischemic stroke mechanism classification. Over the past decades, the hypothesis that different blood-based biomarkers are associated with different ischemic stroke mechanisms is increasingly investigated. This review presents the recent studies that investigated blood-based biomarker characteristics differentiation between ischemic stroke mechanisms. Different blood-based biomarkers are specifically discussed (b-type natriuretic peptide, d-dimer, c-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-1β, neutrophil-lymphocyte ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and apolipoprotein A), as well as the different cut-off values that may be useful in specific classifications for cardioembolic and atherosclerosis etiologies. Lastly, the structure of a point-of-care biosensor device is presented, as a measuring tool on-site. The information presented in this review will hopefully contribute to the major efforts to improve the care for stroke patients.
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Affiliation(s)
- Dorin Harpaz
- School of Material Science & Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore;
- Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel;
| | - Raymond C. S. Seet
- Division of Neurology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore;
| | - Robert S. Marks
- Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel;
| | - Alfred I. Y. Tok
- School of Material Science & Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore;
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Abstract
The relevance of LP(a), Hcy, and D-D in ischemic cerebrovascular disease remains undefined. This study aimed to assess the associations of plasma LP(a), Hcy and D-D levels with the subtype of ischemic cerebrovascular disease.Patients with ischemic cerebrovascular disease admitted to the Taixing People's Hospital were retrospectively enrolled from November 2017 to July 2018. Immunoturbidimetry was used to assess 119 LAA, 107 SAO, and 112 TIA patients for plasma LP(a), Hcy, and D-D levels.Plasma LP(a), Hcy, and D-D levels in the large artery atherosclerosis (LAA) group were significantly lower than those of the transient ischemic attack (TIA) group (all P < .05). LP(a), Hcy, and D-D levels were significantly reduced in the SAO group compared with the TIA group (both P < .05). The LAA and SAO groups showed comparable values for all the above parameters (P > .05).LP(a), Hcy, and D-D levels differ according to the subtype of ischemic cerebrovascular disease.
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Affiliation(s)
- Yong Tang
- Nanjing Medical University, Nanjing
- The Taixing People's Hospital, Taixing, Jiangsu, China
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Zhou Z, Liang Y, Zhang X, Xu J, Kang K, Qu H, Zhao C, Zhao M. Plasma D-Dimer Concentrations and Risk of Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis. Front Neurol 2018; 9:1114. [PMID: 30619067 PMCID: PMC6306414 DOI: 10.3389/fneur.2018.01114] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 12/05/2018] [Indexed: 01/11/2023] Open
Abstract
Background: The aim of our meta-analysis was to evaluate the association between plasma d-dimer and intracerebral hemorrhage (ICH). Methods: Embase, Pubmed, and Web of Science were searched up to the date of March 19th, 2018, and manual searching was used to extract additional articles. Standard mean difference (SMD) with 95% confidence intervals (CI) was calculated to evaluate d-dimer levels. Results: Thirteen studies including 891 ICH patients and 1,573 healthy controls were included. Our results revealed that higher levels of d-dimer were displayed in ICH patients than those in healthy controls (95% CI= 0.98–2.00, p< 0.001). Subgroup analysis based on continent of Asia and Europe, sample size, as well as age in relation to d-dimer levels between ICH patients and healthy controls did not change the initial observation; whereas no differences of d-dimer levels were found between ICH and controls in America. Conclusions: This meta-analysis revealed that high level of d-dimer is associated with the risk of ICH. Plasma d-dimer is suggested to be a potential biomarker for patients with ICH in Asia and Europe rather than in America. There were no impact of sample size-related differences and age-related diversities on the risk of ICH with respect to d-dimer levels.
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Affiliation(s)
- Zhike Zhou
- Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Yifan Liang
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Xiaoqian Zhang
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Junjie Xu
- Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Kexin Kang
- Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Huiling Qu
- Department of Neurology, People's Hospital of Liaoning Province, Shenyang, China
| | - Chuansheng Zhao
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Mei Zhao
- Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang, China
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Zheng J, Cheng C, Zhou C, Chen H, Guo Z, Sun X. The Clinical Value of d-Dimer Level in Patients with Nonaneurysmal Subarachnoid Hemorrhage. World Neurosurg 2018; 114:e1161-e1167. [PMID: 29614358 DOI: 10.1016/j.wneu.2018.03.165] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 03/23/2018] [Accepted: 03/23/2018] [Indexed: 12/23/2022]
Abstract
OBJECTIVE More nonaneurysmal subarachnoid hemorrhage (NaSAH) are found in clinical practice. However, the precise mechanisms in which d-dimer level is associated with clinical condition in patients with NaSAH remain unclear. But even more, the data assessing the risk of clinical course in the patients with NaSAH are scarce. Our objective was to investigate whether d-dimer levels correlated with complication and outcome in patients with NaSAH. METHODS Between February 2013 and May 2017, 92 patients suffering from NaSAH were treated in our hospital. Patient characteristics, radiologic features, laboratory findings, complications, and outcomes were analyzed retrospectively. Patients were stratified into the perimesencephalic (PM) subarachnoid hemorrhage (SAH) group and the nonperimesencephalic (NPM) SAH group according to the bleeding type, and the NPM-SAH group was further divided into 2 subgroups into the NPM-elevated group and the NPM-normal group based on the value of the d-dimer. After statistical analysis, the NPM-SAH and PM-SAH groups were compared; the same was true for the NPM-elevated group and the NPM-normal group. RESULTS The rate of complications in the NPM-SAH group was higher than in the PM-SAH group, including early hydrocephalus, delayed cerebral ischemia, clinical vasospasm, pneumonia, and hyponatremia. Our results showed that d-dimer levels in patients with NPM-SAH were more elevated than in those with PM-SAH. Further analysis of subgroups demonstrated that patients with elevated d-dimer levels had a higher incidence of complications than those with normal d-dimer levels, especially the risks of shunt-dependent hydrocephalus and pneumonia. In addition, disability, and even death, could be seen in patients with higher levels of d-dimer, but the long-term outcomes were not particularly obvious between these groups. CONCLUSIONS Elevated d-dimer levels on admission were significantly associated with complication in patients with NPM-SAH. In addition to conventional radiologic diagnosis, d-dimer levels can increase the ability of a rapid differential diagnosis between NPM-SAH and PM-SAH.
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Affiliation(s)
- Jianfeng Zheng
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, People's Republic of China
| | - Chongjie Cheng
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, People's Republic of China
| | - Chao Zhou
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, People's Republic of China
| | - Hong Chen
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, People's Republic of China
| | - Zongduo Guo
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, People's Republic of China.
| | - Xiaochuan Sun
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, People's Republic of China.
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11
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Fan H, Yang S, Li Y, Yin J, Qin W, Yang L, Yuan J, Hu W. Assessment of Homocysteine as a Diagnostic and Early Prognostic Biomarker for Patients with Acute Lacunar Infarction. Eur Neurol 2017; 79:54-62. [PMID: 29208848 DOI: 10.1159/000484893] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 11/01/2017] [Indexed: 11/19/2022]
Abstract
BACKGROUND Although increasing evidence has demonstrated that elevated homocysteine (Hcy) levels may be an important contributor for the development of cerebral infarction, rare studies focused on its diagnostic and early prognostic roles in acute lacunar infarction. METHODS A total of 197 patients with acute lacunar infarction and 192 to form the control group were prospectively recruited between January 2013 and February 2017. Early neurological deterioration was defined as an increase of ≥2 points in National Institutes of Health Stroke Scale or the decrease in Barthel index (BI) score at discharge. RESULTS Univariate and multivariate logistic regression analyses revealed that higher levels of fibrinogen and Hcy were independently clinical predictors associated with lacunar infarction. Receiver operating characteristic curves analysis demonstrated that the diagnosis value of Hcy was superior to fibrinogen, with the area under the curve of 0.881 and 0.688 respectively. Using the optimal cutoff value of 15.5 μmol/L of Hcy, a sensitivity of 65% and a specificity of 100% were achieved for predicting lacunar infarction. Hcy was only significantly related with BI reduction in the males (30.5 [15.5-65.5] vs. 18 [15-24], p = 0.034) in the univariate analysis but not in the females and the multivariate analysis. CONCLUSIONS Serum Hcy may be an independent diagnostic and not an early prognostic biomarker for patients with acute lacunar infarction.
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12
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Harpaz D, Eltzov E, Seet RCS, Marks RS, Tok AIY. Point-of-Care-Testing in Acute Stroke Management: An Unmet Need Ripe for Technological Harvest. BIOSENSORS 2017; 7:E30. [PMID: 28771209 PMCID: PMC5618036 DOI: 10.3390/bios7030030] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 07/25/2017] [Accepted: 07/26/2017] [Indexed: 12/20/2022]
Abstract
Stroke, the second highest leading cause of death, is caused by an abrupt interruption of blood to the brain. Supply of blood needs to be promptly restored to salvage brain tissues from irreversible neuronal death. Existing assessment of stroke patients is based largely on detailed clinical evaluation that is complemented by neuroimaging methods. However, emerging data point to the potential use of blood-derived biomarkers in aiding clinical decision-making especially in the diagnosis of ischemic stroke, triaging patients for acute reperfusion therapies, and in informing stroke mechanisms and prognosis. The demand for newer techniques to deliver individualized information on-site for incorporation into a time-sensitive work-flow has become greater. In this review, we examine the roles of a portable and easy to use point-of-care-test (POCT) in shortening the time-to-treatment, classifying stroke subtypes and improving patient's outcome. We first examine the conventional stroke management workflow, then highlight situations where a bedside biomarker assessment might aid clinical decision-making. A novel stroke POCT approach is presented, which combines the use of quantitative and multiplex POCT platforms for the detection of specific stroke biomarkers, as well as data-mining tools to drive analytical processes. Further work is needed in the development of POCTs to fulfill an unmet need in acute stroke management.
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Affiliation(s)
- Dorin Harpaz
- Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
- School of Material Science & Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore.
- Institute for Sports Research (ISR), Nanyang Technology University and Loughborough University, Nanyang Avenue, Singapore 639798, Singapore.
| | - Evgeni Eltzov
- Agriculture Research Organization (ARO), Volcani Centre, Rishon LeTsiyon 15159, Israel.
| | - Raymond C S Seet
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore.
| | - Robert S Marks
- Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
- School of Material Science & Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore.
- The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
- The Ilse Katz Centre for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
| | - Alfred I Y Tok
- School of Material Science & Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore.
- Institute for Sports Research (ISR), Nanyang Technology University and Loughborough University, Nanyang Avenue, Singapore 639798, Singapore.
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13
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Hou D, Liu J, Feng R, Gao Y, Wang Y, Wu J. The role of high-sensitivity C-reactive protein levels in functional outcomes in patients with large-artery atherosclerosis and small-artery occlusion. Neurol Res 2017; 39:981-987. [PMID: 28749740 DOI: 10.1080/01616412.2017.1358937] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Dongzhe Hou
- Department of Neurology, Department of Neurorehabilitation, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China
| | - Ji Liu
- Department of Medicine, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China
| | - Ren Feng
- Department of Medical Administration, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China
| | - Yuan Gao
- Department of Neurology, Department of Neurorehabilitation, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China
| | - Yajing Wang
- Department of Neurology, Department of Neurorehabilitation, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China
| | - Jialing Wu
- Department of Neurology, Department of Neurorehabilitation, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin, China
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14
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Sinawang PD, Harpaz D, Fajs L, Seet RCS, Tok AIY, Marks RS. Electrochemical impedimetric detection of stroke biomarker NT-proBNP using disposable screen-printed gold electrodes. EUROBIOTECH JOURNAL 2017. [DOI: 10.24190/issn2564-615x/2017/02.09] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Abstract
Stroke is the second top leading cause of death globally. It is caused by an abrupt interruption of blood flow to the brain. In that course, brain natriuretic peptide (BNP) and its derivative N-terminal pro b-type natriuretic peptide (NT-proBNP), neurohormones produced mainly by the heart ventricles in response to excessive stretching of cardiomyocytes (heart muscle cells), are proven to be good biomarkers for heart failure diagnosis. Moreover, there is growing clinical interest of the use of NT-proBNP for stroke diagnosis and prognosis because it is significantly associated with cardioembolic stroke and secondary stroke reoccurrence, with sensitivity >90% and specificity >80%. However, in diagnostic settings, there is still a need to address the encountered analytical problems, particularly assay specificity and set up. In this study, a novel approach for NT-proBNP detection is demonstrated using an electrochemical immunoassay method. A label-free impedimetry immunosensor for stroke biomarker was developed using modified disposable screen-printed gold electrodes (SPGE) hosting specific anti-NT-proBNP capture antibody. The performance of our immunosensor was studied in the presence of NT-proBNP in both buffered and mock (porcine) plasma samples. A linear relation between the relative total resistance (ΔRtot) responses and the NT-proBNP concentrations in buffer was observed in a range from 0.1 to 5 ng mL-1 with a correlation coefficient (R2) of 0.94656. Overall, the biosensor has demonstrated the capability to quantitate NT-proBNP and differentiate such concentrations in a low concentration range, especially among 0, 0.1, 0.5, 1, and 3 ng mL-1 in plasma samples within 25 min. This range is valuable not only for classifying cardioembolic stroke (higher or equal to 0.5 ng mL-1), but also predicting the risk of secondary stroke reoccurrence (higher than 0.255 ng mL-1). Our biosensor has the potential to be used as an easy-to-use point-of-care test that is both accurate and affordable.
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Affiliation(s)
- Prima Dewi Sinawang
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
- Biosensorix Pte. Ltd., 1 Raffles Place, Singapore 048616, Singapore
| | - Dorin Harpaz
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
- The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev , Israel
- Institute for Sports Research, Nanyang Technological University, Singapore
| | - Luka Fajs
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
- Biosensorix Pte. Ltd., 1 Raffles Place, Singapore 048616, Singapore
| | - Raymond Chee Seong Seet
- Division of Neurology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore , Singapore
| | - Alfred Iing Yoong Tok
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
- Institute for Sports Research, Nanyang Technological University, Singapore
| | - Robert S. Marks
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
- The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev , Israel
- The National Institute for Biotechnology, The Ilse Katz Center for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev , Israel
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Lee JH, Kim KJ, Kim MK, Yoo BG. D-dimer Predicts Short-Term Functional Outcome in Acute Ischemic Stroke. JOURNAL OF NEUROCRITICAL CARE 2017. [DOI: 10.18700/jnc.160084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Bonaventura A, Liberale L, Vecchié A, Casula M, Carbone F, Dallegri F, Montecucco F. Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke. Int J Mol Sci 2016; 17:1967. [PMID: 27898011 PMCID: PMC5187767 DOI: 10.3390/ijms17121967] [Citation(s) in RCA: 111] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Revised: 11/08/2016] [Accepted: 11/17/2016] [Indexed: 12/26/2022] Open
Abstract
After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies.
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Affiliation(s)
- Aldo Bonaventura
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
| | - Alessandra Vecchié
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
| | - Matteo Casula
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
| | - Franco Dallegri
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
- IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, 10 Largo Benzi, 16132 Genoa, Italy.
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
- IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, 10 Largo Benzi, 16132 Genoa, Italy.
- Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy.
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Yang XY, Gao S, Ding J, Chen Y, Zhou XS, Wang JE. Plasma D-dimer predicts short-term poor outcome after acute ischemic stroke. PLoS One 2014; 9:e89756. [PMID: 24587013 PMCID: PMC3933671 DOI: 10.1371/journal.pone.0089756] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 01/23/2014] [Indexed: 11/21/2022] Open
Abstract
Objective Haemostatic biomarkers associated with poor outcome in acute ischemic stroke (AIS). The objective of the study was to evaluate the predictive value of plasma D-dimer (D-D) on functional outcome at 90-day follow-up from stroke onset. Methods We conducted a prospective, observational cohort study in the emergency department and enrolled 220 patients with AIS. Plasma D-D concentrations, determined by a particle-enhanced, immunoturbidimetric assay, were measured. Each patient’s medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Results There was a positive correlation between levels of D-D and the NIHSS (r = 0.361, p<0.001), and the infarct volume (r = 0.449, p<0.001). In the 69 patients with an unfavorable functional outcome, D-D levels were higher compared with those in patients with a favorable outcome [3.24(IQR, 2.18–4.60)mg/L vs 0.88(IQR, 0.35–1.77) mg/L; p<0.001]. After adjusting for all other significant outcome predictors, D-D level remained an independent predictor for unfavorable functional outcome and mortality with an odds ratio of 2.18 (95% CI, 1.55–2.83), 3.22 (95% CI, 2.05–6.43); respectively. Conclusions D-D levels are a useful tool to predict outcome and mortality 90-day after acute ischemic stroke and have a potential to assist clinicians.
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Affiliation(s)
- Xiao-ying Yang
- Department of Clinical Laboratory, Shanghai Jiao Tong University, Affiliated the Sixth People Hospital Fengxian Branch, Shanghai, P. R. China
| | - Shan Gao
- Department of Neurology, Shanghai Jiao Tong University, Affiliated the Sixth People Hospital Fengxian Branch, Shanghai, P. R. China
- * E-mail:
| | - Jie Ding
- Department of Neurology, Tianjin Union Medicine Center, Tianjin, P. R. China
| | - Yan Chen
- Department of Neurology, Shanghai Jiao Tong University, Affiliated the Sixth People Hospital Fengxian Branch, Shanghai, P. R. China
| | - Xing-sheng Zhou
- Department of Neurology, Shanghai Jiao Tong University, Affiliated the Sixth People Hospital Fengxian Branch, Shanghai, P. R. China
| | - Jing-E Wang
- Department of Neurology, Shanghai Jiao Tong University, Affiliated the Sixth People Hospital Fengxian Branch, Shanghai, P. R. China
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