scholarly journals Circulating Circular RNAs as Biomarkers for the Diagnosis and Prediction of Outcomes in Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (1) ◽  
pp. 319-323 ◽  
Author(s):  
Lei Zuo ◽  
Lin Zhang ◽  
Juan Zu ◽  
Zan Wang ◽  
Bing Han ◽  
...  

Background and Purpose— Circular RNAs (CircRNAs) show promise as stroke biomarkers because of their participation in various pathophysiological processes associated with acute ischemic stroke (AIS) and stability in peripheral blood. Methods— A circRNA microarray was used to identify differentially expressed circulating circRNAs in a discovery cohort (3 versus 3). Validation (36 versus 36) and replication (200 versus 100) were performed in independent cohorts by quantitative polymerase chain reaction. Platelets, lymphocytes, and granulocytes were separated from blood to examine the origins of circRNAs. Results— There were 3 upregulated circRNAs in Chinese population–based AIS patients compared with healthy controls. The combination of 3 circRNAs resulted in an area under the curve of 0.875, corresponding to a specificity of 91% and a sensitivity of 71.5% in AIS diagnosis. Furthermore, the combination of change rate in 3 circRNAs within the first 7 days of treatment showed an area under the curve of 0.960 in predicting stroke outcome. There was significant increase in lymphocytes and granulocytes for circPDS5B (circular RNA PDS5B) and only in granulocytes for circCDC14A (circular RNA CDC14A) in AIS patients compared with healthy controls. Conclusions— Three circRNAs could serve as biomarkers for AIS diagnosis and prediction of stroke outcomes. The elevated levels of circPDS5B and circCDC14A after stroke might be because of increased levels in lymphocytes and granulocytes.

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Lei Zuo ◽  
Cai Li ◽  
Juan Zu ◽  
Honghong Yao ◽  
Fuling Yan

Abstract Identifying those patients who were at high risk of stroke associated infection (SAI) for preventive antibiotic therapy was imperative for patients’ benefits, thus improving prediction of SAI was critical for all acute ischemic stroke (AIS) patients. Circular RNA FUNDC1 (circFUNDC1) has been reported to be the diagnosis and prognosis biomarker of AIS. Therefore, the present study aimed to figure out whether circFUNDC1 could be the potential predictor of SAI that could help to guide preventive treatment. In total, 68 patients were included in the study, 26 of which had infection and 42 without. Copy number of circFUNDC1 in plasma were quantified by quantitative real-time polymerase chain reaction (qPCR). Platelet spike-in experiment and correlation analysis were conducted to explore possible origins of circFUNDC1 in plasma. A significantly elevated level of circFUNDC1 was found in SAI patients compared with not infected AIS patients (P=0.0258). Receiver operating characteristic (ROC) curves demonstrated the prediction significance of circFUNDC1, with the area under the curve (AUC) at 0.6612 and sensitivity, specificity at 69.23%, 61.90% respectively in predicting SAI. Then, when adding circFUNDC1 in the risk model, the AUC increased from 0.7971 in model A to 0.8038 in model B. Additionally, positive correlation was observed between circFUNDC1 level and neutrophils counts. WBC and neutrophil ratios were significantly elevated in SAI patients compared with non-SAI patients. Therefore, circFUNDC1 could be used to construct a risk model for the prediction of SAI that is beneficial for AIS patients’ preventive treatment.


2019 ◽  
Author(s):  
Yunlong Ding ◽  
Yazhou Yan ◽  
Jiali Niu ◽  
Yanrong Zhang ◽  
Zhiqun Gu ◽  
...  

Abstract Background Prevention of pneumonia is critical for patients with acute ischemic stroke (AIS). The six indexes in the Braden Scale seemsto be related to the occurrence of pneumonia. We aimed to evaluate the feasibility of the Braden Scale in predicting the occurrence of pneumonia after AIS. Methods We studied a series of consecutive patients with AIS who were admitted to hospital. The cohort was subdivided into pneumonia group and no pneumonia group. The score of the Braden Scale, demographic and clinical characteristics at admission were obtained and analyzed by statistical comparisons between two groups. We investigated the predictive validity of the Braden scale by Receiver operating curve (ROC). Results 414 patients with AIS were included in this study. 57 of 414 (13.8%) patients fulfilled the criteria for post-stroke pneumonia. The National Institutes of Health Stroke Scale (NIHSS) score in the pneumonia group was significantly higher than in the no pneumonia group (P < 0.01). The mean score of the Braden Scale in the pneumonia group was significantly lower than that in the no pneumonia group (P < 0.01). The six subscales of the Braden Scale between the two groups all had significant differences. The area under the curve (AUC) for the Braden scale predicting pneumonia after acute ischemic was 0.883 (95% CI = 0.828-0.937). And with 18 points as the demarcation score, the sensitivity was 83.2% and the specificity was 84.2%. Conclusion The Braden Scale with 18 points as the demarcation score is a valid clinical grading scale for predicting pneumonia after AIS at presentation. Further studies on effect of Braden Scale on stroke outcomes are needed.


2019 ◽  
Vol 1 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Sarah Yaziz ◽  
Ahmad Sobri Muda ◽  
Wan Asyraf Wan Zaidi ◽  
Nik Azuan Nik Ismail

Background : The clot burden score (CBS) is a scoring system used in acute ischemic stroke (AIS) to predict patient outcome and guide treatment decision. However, CBS is not routinely practiced in many institutions. This study aimed to investigate the feasibility of CBS as a relevant predictor of good clinical outcome in AIS cases. Methods:  A retrospective data collection and review of AIS patients in a teaching hospital was done from June 2010 until June 2015. Patients were selected following the inclusion and exclusion criteria. These patients were followed up after 90 days of discharge. The Modified Rankin scale (mRS) was used to assess their outcome (functional status). Linear regression Spearman Rank correlation was performed between the CBS and mRS. The quality performance of the correlations was evaluated using Receiver operating characteristic (ROC) curves. Results: A total of 89 patients with AIS were analysed, 67.4% (n=60) male and 32.6% (n=29) female. Twenty-nine (29) patients (33.7%) had a CBS ?6, 6 patients (6.7%) had CBS <6, while 53 patients (59.6%) were deemed clot free. Ninety (90) days post insult, clinical assessment showed that 57 (67.6%) patients were functionally independent, 27 (30.3%) patients functionally dependent, and 5 (5.6%) patients were deceased. Data analysis reported a significant negative correlation (r= -0.611, p<0.001). ROC curves analysis showed an area under the curve of 0.81 at the cut-off point of 6.5. This showed that a CBS of more than 6 predicted a good mRS clinical outcome in AIS patients; with sensitivity of 98.2%, specificity of 53.1%, positive predictive value (PPV) of 76%, and negative predictive value (NPV) of 21%. Conclusion: CBS is a useful additional variable for the management of AIS cases, and should be incorporated into the routine radiological reporting for acute ischemic stroke (AIS) cases.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hanaa A. El-Gendy ◽  
Mahmoud A. Mohamed ◽  
Amr E. Abd-Elhamid ◽  
Mohammed A. Nosseir

Abstract Background Hyperglycemia is a risk factor for infarct expansion and poor outcome for both diabetic and non-diabetic patients. We aimed to study the prognostic value of stress hyperglycemia on the outcome of acute ischemic stroke patients as regards National Institutes of Health Stroke Scale (NIHSS) as a primary outcome. Results Patients with high random blood sugar (RBS) on admission showed significantly higher values of both median NIHSS score and median duration of hospital stay. There were significant associations between stress hyperglycemia and the risk of 30-day mortality (p < 0.001), the need for mechanical ventilation (p < 0.001) and vasopressors (p < 0.001), and the occurrence of hemorrhagic transformation (p = 0.001). The 24-h RBS levels at a cut off > 145 mg/dl showed a significantly good discrimination power for 30-day mortality (area under the curve = 0.809). Conclusions Stress hyperglycemia had a prognostic value and was associated with less-favorable outcomes of acute stroke patients. Therefore, early glycemic control is recommended for those patients.


2016 ◽  
Vol 42 (1-2) ◽  
pp. 81-89 ◽  
Author(s):  
Mohamed Al-Khaled ◽  
Christine Matthis ◽  
Andreas Binder ◽  
Jonas Mudter ◽  
Joern Schattschneider ◽  
...  

Background: Dysphagia is associated with poor outcome in stroke patients. Studies investigating the association of dysphagia and early dysphagia screening (EDS) with outcomes in patients with acute ischemic stroke (AIS) are rare. The aims of our study are to investigate the association of dysphagia and EDS within 24 h with stroke-related pneumonia and outcomes. Methods: Over a 4.5-year period (starting November 2007), all consecutive AIS patients from 15 hospitals in Schleswig-Holstein, Germany, were prospectively evaluated. The primary outcomes were stroke-related pneumonia during hospitalization, mortality, and disability measured on the modified Rankin Scale ≥2-5, in which 2 indicates an independence/slight disability to 5 severe disability. Results: Of 12,276 patients (mean age 73 ± 13; 49% women), 9,164 patients (74%) underwent dysphagia screening; of these patients, 55, 39, 4.7, and 1.5% of patients had been screened for dysphagia within 3, 3 to <24, 24 to ≤72, and >72 h following admission. Patients who underwent dysphagia screening were likely to be older, more affected on the National Institutes of Health Stroke Scale score, and to have higher rates of neurological symptoms and risk factors than patients who were not screened. A total of 3,083 patients (25.1%; 95% CI 24.4-25.8) had dysphagia. The frequency of dysphagia was higher in patients who had undergone dysphagia screening than in those who had not (30 vs. 11.1%; p < 0.001). During hospitalization (mean 9 days), 1,271 patients (10.2%; 95% CI 9.7-10.8) suffered from stroke-related pneumonia. Patients with dysphagia had a higher rate of pneumonia than those without dysphagia (29.7 vs. 3.7%; p < 0.001). Logistic regression revealed that dysphagia was associated with increased risk of stroke-related pneumonia (OR 3.4; 95% CI 2.8-4.2; p < 0.001), case fatality during hospitalization (OR 2.8; 95% CI 2.1-3.7; p < 0.001) and disability at discharge (OR 2.0; 95% CI 1.6-2.3; p < 0.001). EDS within 24 h of admission appeared to be associated with decreased risk of stroke-related pneumonia (OR 0.68; 95% CI 0.52-0.89; p = 0.006) and disability at discharge (OR 0.60; 95% CI 0.46-0.77; p < 0.001). Furthermore, dysphagia was independently correlated with an increase in mortality (OR 3.2; 95% CI 2.4-4.2; p < 0.001) and disability (OR 2.3; 95% CI 1.8-3.0; p < 0.001) at 3 months after stroke. The rate of 3-month disability was lower in patients who had received EDS (52 vs. 40.7%; p = 0.003), albeit an association in the logistic regression was not found (OR 0.78; 95% CI 0.51-1.2; p = 0.2). Conclusions: Dysphagia exposes stroke patients to a higher risk of pneumonia, disability, and death, whereas an EDS seems to be associated with reduced risk of stroke-related pneumonia and disability.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sungmin Hong ◽  
Anne-katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Anna Bonkhoff ◽  
...  

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.


2018 ◽  
Vol 27 (12) ◽  
pp. 1763-1777 ◽  
Author(s):  
Sheng-Wen Wang ◽  
Zhong Liu ◽  
Zhong-Song Shi

Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.


Author(s):  
Tiberiu A. Pana ◽  
Dana K. Dawson ◽  
Mohamed O. Mohamed ◽  
Fiona Murray ◽  
David L. Fischman ◽  
...  

Background The association between systemic hypertension and cerebrovascular disease is well documented. However, the impact of pulmonary hypertension (PH) on acute ischemic stroke outcomes is unknown despite PH being recognized as a risk factor for acute ischemic stroke. We aimed to determine the association between PH and adverse in‐hospital outcomes after acute ischemic stroke, as well as whether there are sex differences in this association. Methods and Results Acute ischemic stroke admissions from the US National Inpatient Sample between October 2015 and December 2017 were included. The relationship between PH and outcomes (mortality, prolonged hospitalization >4 days, and routine home discharge) was analyzed using logistic regressions adjusting for demographics, comorbidities, and revascularization therapies. Interaction terms between PH and sex and age groups were also included. A total of 221 249 records representative of 1 106 045 admissions were included; 2.9% of patients had co‐morbid PH, and 35.34% of those were male. PH was not associated with in‐hospital mortality (odds ratio [OR], 0.96; 95% CI, 0.86–1.09) but was associated with increased odds of prolonged hospitalization (OR, 1.15; 95% CI, 1.09–1.22) and decreased odds of routine discharge (OR, 0.87; 95% CI, 0.81–0.94) for both sexes. Older patients with PH were significantly less likely to be discharged routinely ( P =0.028) than their younger counterparts. Compared with female patients with PH, men were 31% more likely to die in hospital ( P =0.024). Conclusions PH was not significantly associated with in‐hospital mortality but was associated with prolonged hospitalization and adverse discharge status. Male patients with PH were more likely to die in hospital than female patients.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Leticia C Rebello ◽  
Aaron Anderson ◽  
Diogo C Haussen ◽  
Samir R Belagaje ◽  
Jonathan A Grossberg ◽  
...  

Background: The ethnic disparities in stroke outcomes have been well described. Stroke is twice more common and leads to higher mortality rates among blacks as compared to whites. We compared the outcomes of patients undergoing endovascular stroke therapy (ET) in a high-volume center according to their racial profile after age adjustment. Methods: Retrospective analysis of a prospectively collected ET database between September/2010-September/2015. The baseline characteristics of African-American vs. Caucasian patients were compared. Given the impact of age on stroke outcomes additional analyses were performed dichotomizing patients using the median age of the overall cohort. Primary and secondary efficacy outcomes included the rates of good outcome (90-day mRS 0-2) and successful reperfusion (mTICI 2b-3), respectively. Safety outcome was accessed by rates of any parenchymal hematoma (PH-1 and PH-2) and 90-day mortality. Results: 781 patients fit the inclusion criteria and were included in the analysis; 440 were included in the Caucasian group (56% overall cohort) and 341 in the African-American group (44%). Caucasian patients were significantly older (69±13 vs. 60±14 years-old, p<0.01) but the remaining baseline characteristics were otherwise well-balanced. This included similar baseline CT perfusion core volumes (rCBF<30%, 17.6 ± 20.8 vs. 17.9 ± 32.8; p=0.93). There were no differences in the rates successful reperfusion (mTICI 2b-3: 83% vs. 85%, p=0.37), any PH (8% vs. 5%, p=0.26), or final infarct volume (32 IQR 12-89 vs. 25 IQR 9-67; p=0.12) across the two groups. In the overall cohort, there was a lower proportion of 90-day good outcome (39% vs. 49%; p<0.01) and higher 90-day mortality (32% vs. 16%; p<0.01) among Caucasians presumably due to their older age. Subgroup analysis of patients 65 years-old or younger showed similar rates of 90-day good outcomes (59% vs. 53%; p=0.33) and mortality (17% vs. 12%; p=0.22) across Caucasian and African-American patients. Conclusion: Aggressive treatment of acute ischemic stroke with endovascular therapy leads to similar outcomes across African-American and Caucasian patients. Greater availability of ET may diminish the ethnic/racial disparities in stroke outcomes.


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