Circular RNA FUNDC1 improves prediction of stroke associated infection in acute ischemic stroke patients with high risk

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.

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Evaluation of the clot burden score (cbs) for acute ischemic stroke (ais) in intent-to-treat patients.

Journal Of Cardiovascular, Neurovascular & Stroke ◽

10.32896/cvns.v1n1.11-15 ◽

2019 ◽

Vol 1 (1) ◽

pp. 11-15 ◽

Cited By ~ 1

Author(s):

Sarah Yaziz ◽

Ahmad Sobri Muda ◽

Wan Asyraf Wan Zaidi ◽

Nik Azuan Nik Ismail

Keyword(s):

Ischemic Stroke ◽

Clinical Outcome ◽

Acute Ischemic Stroke ◽

Predictive Value ◽

Area Under The Curve ◽

Rank Correlation ◽

Treatment Decision ◽

Roc Curves ◽

Significant Negative Correlation ◽

Clot Burden

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.

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

Stroke ◽

10.1161/strokeaha.119.027348 ◽

2020 ◽

Vol 51 (1) ◽

pp. 319-323 ◽

Cited By ~ 7

Author(s):

Lei Zuo ◽

Lin Zhang ◽

Juan Zu ◽

Zan Wang ◽

Bing Han ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Quantitative Polymerase Chain Reaction ◽

Area Under The Curve ◽

Circular Rna ◽

Population Based ◽

Circular Rnas ◽

Healthy Controls ◽

Change Rate ◽

Stroke Outcomes

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.

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Abstract P212: Comparison Of Vascular Risk Factors And Serum Fatty Acids At Admission Between Intracerebral Hemorrhage And Acute Ischemic Stroke

Circulation ◽

10.1161/circ.143.suppl_1.p212 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Takahisa Mori ◽

Kazuhiro Yoshioka ◽

Yuichi Miyazaki

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Acute Ischemic Stroke ◽

Area Under The Curve ◽

Density Lipoprotein ◽

Correlation Coefficients ◽

Roc Curves ◽

Threshold Values ◽

Independent Variables ◽

Average Blood Pressure

Introduction: Dietary triglycerides influence fatty acid (FA) serum concentrations and weight percentages (wt%), which may be associated with the onset of intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS). Hypothesis: There are significant differences between FAs at the admission of ICH and AIS. Methods: We included patients admitted between 2016 and 2019 within 24 h of ICH or AIS onset and calculated correlation coefficients between their ages, serum FA concentrations, and FA wt% values. We evaluated differences in age, average blood pressure (ABP), glucose, A1c, serum lipids, and FAs between two groups. Excluding variables with multicollinearity, we performed multiple logistic regression (MLR) analysis to identify independent variables distinguishing ICH from AIS. We estimated the threshold values of independent variables using the area under the curve values derived from the receiver operating characteristic (ROC) curves. Results: Our inclusion criteria were met by 141 of ICH patients and 525 of AIS patients. In the ICH group, age, A1c, and eicosapentaenoic acid (EPA) levels were smaller than those in the AIS group. ABP, high-density lipoprotein cholesterol (HDL-C), myristic acid (MyA), linoleic acid (LiA) concentrations, and MyA wt% were higher than those in the AIS group. MLR analysis between two groups indicated that age, ABP, A1c, HDL-C were independent variables. Serum FA levels were not independent. ROC curves showed that the threshold values of age, ABP, A1c, and HDL-C for ICH onset were ≤ 69 years, ≥ 126.6 mmHg, ≤ 6.0%, and ≥ 1.62 mmol/L, respectively. In 27 patients with age ≤ 69 , ABP ≥ 126.6, A1c ≤ 6.0%, and HDL-C ≥ 1.62 and 87 patients with age > 69 , ABP< 126.6, A1c > 6.0, and HDL-C < 1.62, there were 19 (70.4%) and 9 (10.3%) patients with ICH, the MyA concentrations were 108 and 73 μmol/L (p < 0.001), the LiA concentration were 2,900 and 2,410μmol/L (p < 0.001), and the EPA wt% were 1.4 and 2.0% (p=0.059), respectively. Conclusions: Younger patients with higher ABP, lower A1c, and higher HDL-C suffered from not AIS but ICH, and their MyA and LiA concentrations were higher than older patients without them.

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Evaluation of the clot burden score (cbs) for acute ischemic stroke (ais) in intent-to-treat patients.

Journal Of Cardiovascular, Neurovascular & Stroke ◽

10.32896/cvns.11.11-15 ◽

2019 ◽

pp. 11-15

Author(s):

Sarah Yaziz ◽

Ahmad Sobri Muda ◽

Wan Asyraf Wan Zaidi ◽

Nik Azuan Nik Ismail

Keyword(s):

Ischemic Stroke ◽

Clinical Outcome ◽

Acute Ischemic Stroke ◽

Predictive Value ◽

Area Under The Curve ◽

Rank Correlation ◽

Treatment Decision ◽

Roc Curves ◽

Significant Negative Correlation ◽

Clot Burden

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Predictive value of time-variant color-coded multiphase CT angiography (mCTA) regarding clinical outcome of acute ischemic stroke: in comparison with conventional mCTA and CT perfusion

Acta Radiologica ◽

10.1177/0284185120981770 ◽

2020 ◽

pp. 028418512098177

Author(s):

Yu Lin ◽

Nannan Kang ◽

Jianghe Kang ◽

Shaomao Lv ◽

Jinan Wang

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Predictive Value ◽

Ct Perfusion ◽

Roc Curves ◽

Multivariate Logistic Regression Model ◽

Infarct Core ◽

Predictive Values ◽

Significant Difference ◽

Core Volume

Background Color-coded multiphase computed tomography angiography (mCTA) can provide time-variant blood flow information of collateral circulation for acute ischemic stroke (AIS). Purpose To compare the predictive values of color-coded mCTA, conventional mCTA, and CT perfusion (CTP) for the clinical outcomes of patients with AIS. Material and Methods Consecutive patients with anterior circulation AIS were retrospectively reviewed at our center. Baseline collateral scores of color-coded mCTA and conventional mCTA were assessed by a 6-point scale. The reliabilities between junior and senior observers were assessed by weighted Kappa coefficients. Receiver operating characteristic (ROC) curves and multivariate logistic regression model were applied to evaluate the predictive capabilities of color-coded mCTA and conventional mCTA scores, and CTP parameters (hypoperfusion and infarct core volume) for a favorable outcome of AIS. Results A total of 138 patients (including 70 cases of good outcomes) were included in our study. Patients with favorable prognoses were correlated with better collateral circulations on both color-coded and conventional mCTA, and smaller hypoperfusion and infarct core volume (all P < 0.05) on CTP. ROC curves revealed no significant difference between the predictive capability of color-coded and conventional mCTA ( P = 0.427). The predictive value of CTP parameters tended to be inferior to that of color-coded mCTA score (all P < 0.001). Both junior and senior observers had consistently excellent performances (κ = 0.89) when analyzing color-coded mCTA maps. Conclusion Color-coded mCTA provides prognostic information of patients with AIS equivalent to or better than that of conventional mCTA and CTP. Junior radiologists can reach high diagnostic accuracy when interpreting color-coded mCTA images.

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Stress hyperglycemia as a prognostic factor in acute ischemic stroke patients: a prospective observational cohort study

Ain-Shams Journal of Anesthesiology ◽

10.1186/s42077-020-00122-6 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Hanaa A. El-Gendy ◽

Mahmoud A. Mohamed ◽

Amr E. Abd-Elhamid ◽

Mohammed A. Nosseir

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Prognostic Value ◽

Area Under The Curve ◽

Hemorrhagic Transformation ◽

Diabetic Patients ◽

Stroke Patients ◽

Stress Hyperglycemia ◽

Discrimination Power ◽

Observational Cohort

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.

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Abstract 2771: Incidence of High Risk Atherosclerotic Lesions in Intracranial and Extracranial Carotid Arteries in Patients with Acute Ischemic Stroke: A 3.0T Magnetic Resonance Imaging Study

Stroke ◽

10.1161/str.43.suppl_1.a2771 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Xihai Zhao ◽

Huilin Zhao ◽

Feiyu Li ◽

Jie Sun ◽

Ye Cao ◽

...

Keyword(s):

Ischemic Stroke ◽

High Risk ◽

Carotid Artery ◽

Acute Ischemic Stroke ◽

Cerebral Artery ◽

Carotid Arteries ◽

Atherosclerotic Plaques ◽

Slice Thickness ◽

Atherosclerotic Lesions ◽

Vascular Beds

Introduction Rupture of vulnerable atherosclerotic plaques in the intracranial and extracranial carotid arteries could trigger ischemic stroke. However, the incidence of high risk atherosclerotic lesions in these vascular beds is not well known. This study sought to investigate the incidence of high risk atherosclerotic lesions in intracranial and extracranial carotid arteries in stroke patients using magnetic resonance (MR) imaging. Methods Seventy-five patients (mean age 62.7 years, 56 males) with acute ischemic stroke underwent MR imaging for index carotid arteries, assigned as the same side as the brain lesions, with a Philips 3.0T MR scanner. Intracranial carotid MR angiography was performed using 3D TOF sequence with FOV of 23 × 23 cm 2 , matrix of 256 × 256, and a slice thickness of 1mm. The multi-contrast vessel wall images (3D TOF, T1W, T2W, and MP-RAGE) were acquired for extracranial carotid arteries with FOV of 14 × 14 cm 2 , matrix of 256 × 256, and slice thickness of 2 mm. The intracranial artery includes middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA). The extracranial carotid artery was divided into internal carotid artery (ICA), bulb, and common carotid artery (CCA). Luminal stenosis for each intracranial and extracranial carotid segment was measured and graded (normal or mild = 0-29%, moderate =30-69%, severe=70-99%). Normalized wall index (NWI = wall area/total vessel area × 100%), and presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) and/or fibrous cap rupture in each extracranial carotid segment were determined. Results MCAs developed more severe stenotic lesions (24.6%), followed by extracranial carotids (16.5%), PCAs (5.4%), and ACAs (4.1%) in stroke patients ( Figure 1 A). For extracranial carotid arteries, ICAs showed the largest plaque burden as measured by NWI (44.3%±13.1%), followed by bulbs (39.4%±13%), and CCAs (37%±6.8%). Compared to CCAs, ICAs and bulb regions had more LRNCs (38.4% and 49.3% for ICA and bulb respectively) and IPH and/or rupture (11% and 9.6% for ICA and bulb respectively) ( Figure 1 B). Conclusions In patients with acute ischemic stroke, high risk atherosclerotic plaques can be found in both intracranial and extracranial carotid arteries, particularly in the MCA, ICA and bulb regions. Compared to extracranial carotid arteries, intracranial arteries develop more high risk lesions. The findings of this study suggest the necessity for early screening to detect high risk atherosclerotic lesions in these carotid vascular beds prior to cerebravascular events.

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Identification of the most specific markers to differentiate primary pulmonary carcinoma from metastatic gastrointestinal carcinoma to the lung

Diagnostic Pathology ◽

10.1186/s13000-021-01184-2 ◽

2022 ◽

Vol 17 (1) ◽

Author(s):

Bachar Alabdullah ◽

Amir Hadji-Ashrafy

Keyword(s):

Gastrointestinal Tract ◽

Predictive Value ◽

Regression Models ◽

Area Under The Curve ◽

Roc Curves ◽

Multivariate Models ◽

Gastrointestinal Carcinoma ◽

Lung Tumours ◽

Napsin A ◽

Sensitivity Specificity

Abstract Background A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, however, a standardised panel for that purpose does not exist yet. We aimed to identify the smallest panel that is most sensitive and specific at differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract. Methods A total of 170 samples were collected, including 140 primary and 30 non-primary lung tumours and staining for CK7, Napsin-A, TTF1, CK20, CDX2, and SATB2 was performed via tissue microarray. The data was then analysed using univariate regression models and a combination of multivariate regression models and Receiver Operating Characteristic (ROC) curves. Results Univariate regression models confirmed the 6 biomarkers’ ability to independently predict the primary outcome (p < 0.001). Multivariate models of 2-biomarker combinations identified 11 combinations with statistically significant odds ratios (ORs) (p < 0.05), of which TTF1/CDX2 had the highest area under the curve (AUC) (0.983, 0.960–1.000 95% CI). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.7, 100, 100, and 37.5% respectively. Multivariate models of 3-biomarker combinations identified 4 combinations with statistically significant ORs (p < 0.05), of which CK7/CK20/SATB2 had the highest AUC (0.965, 0.930–1.000 95% CI). The sensitivity, specificity, PPV, and NPV were 85.1, 100, 100, and 41.7% respectively. Multivariate models of 4-biomarker combinations did not identify any combinations with statistically significant ORs (p < 0.05). Conclusions The analysis identified the combination of CK7/CK20/SATB2 to be the smallest panel with the highest sensitivity (85.1%) and specificity (100%) for predicting tumour origin with an ROC AUC of 0.965 (p < 0.001; SE: 0.018, 0.930–1.000 95% CI).

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Abstract P348: Perfusion Collateral Index vs. Hypoperfusion Intensity Ratio in Assessment of Angiographic Collateral Scores in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.p348 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Brian Tsui ◽

Iris Chen ◽

Joe Qiao ◽

Kasra Khatibi ◽

Lucido Ponce Mejia ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Perfusion Imaging ◽

Intensity Ratio ◽

Roc Analysis ◽

Cerebral Blood Volume ◽

Imaging Biomarker ◽

Lesion Volume ◽

Significant Difference ◽

Sensitivity Specificity

Background and Purpose: In acute ischemic stroke (AIS), perfusion imaging, while not directly visualizing collateral vessels, can provide important insight into collateral robustness, indexed by perfusion lesion volume and by perfusion lesion heterogeneity. Two proposed perfusion lesion heterogeneity measures indexing collateral status are the Perfusion Collateral Index (PCI) and Hypoperfusion Intensity Ratio (HIR), but their accuracy compared with direct collateral assessment on DSA has been incompletely characterized. Methods: Consecutive AIS patients with anterior circulation large vessel occlusion who underwent pre-endovascular thrombectomy MRI perfusion imaging were included. MRI measures analyzed were: 1) Perfusion Collateral Index ( PCI) - the volume of moderately hypoperfused tissue (arterial tissue delay time between 2 and 6 seconds: ATD 2-6sec ) multiplied by its corresponding relative cerebral blood volume using Olea software; 2) Hypoperfusion Intensity Ratio (HIR) ratio of moderate TMax >6 s lesion volume versus severe Tmax >10 s lesion volume with the RAPID software program. DSA collateral scores were evaluated by ASITN grading and dichotomized to inadequate (ASTIN <2) vs. adequate (ASTIN ≥3). Results: Among 48 patients meeting entry criteria, age (mean ± SD) was 70 (± 15.2), 54% were female, and NIHSS (median, IQR) was 15 (10-19). For HIR, there was no significant difference in score values in patients with adequate vs inadequate collaterals: 0.35 ± 0.20 vs 0.39 ± 0.25, p=0.68. ROC analysis using previously described cut-off of 0.4 resulted in an AUC of 0.52 and sensitivity/specificity of 71% / 33%. For PCI, score values were significantly higher in patients with adequate vs inadequate collaterals, 117 ± 61 vs. 57 ± 41, p=0.002. ROC analysis using previously described cut-off of 62 resulted in an AUC of 0.8 and sensitivity/specificity of 84% / 78%. Conclusion: Collateral status can be accurately assessed on perfusion MRI with the Perfusion Collateral Index, which outperformed the Hypoperfusion Intensity Ratio. MRI-PCI is an informative imaging biomarker of collateral status in patients with AIS.

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