scholarly journals Association of Matrix Metalloproteinase 9 and Cellular Fibronectin and Outcome in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Lu Wang ◽  
Linghui Deng ◽  
Ruozhen Yuan ◽  
Junfeng Liu ◽  
Yuxiao Li ◽  
...  

Introduction: The role of matrix metalloproteinase 9 (MMP-9) and cellular fibronectin (c-Fn) in acute ischemic stroke is controversial. We systematically reviewed the literature to investigate the association of circulating MMP-9 and c-Fn levels and MMP-9 rs3918242 polymorphism with the risk of three outcome measures after stroke.Methods: We searched English and Chinese databases to identify eligible studies. Outcomes included severe brain edema, hemorrhagic transformation, and poor outcome (modified Rankin scale score ≥3). We estimated standardized mean differences (SMDs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs).Results: Totally, 28 studies involving 7,239 patients were included in the analysis of circulating MMP-9 and c-Fn levels. Meta-analysis indicated higher levels of MMP-9 in patients with severe brain edema (SMD, 0.76; 95% CI, 0.18–1.35; four studies, 419 patients) and hemorrhagic transformation (SMD, 1.00; 95% CI, 0.41–1.59; 11 studies, 1,709 patients) but not poor outcome (SMD, 0.30; 95% CI, −0.12 to 0.72; four studies, 759 patients). Circulating c-Fn levels were also significantly higher in patients with severe brain edema (SMD, 1.55; 95% CI, 1.18–1.93; four studies, 419 patients), hemorrhagic transformation (SMD, 1.75; 95% CI, 0.72–2.78; four studies, 458 patients), and poor outcome (SMD, 0.46; 95% CI, 0.16–0.76; two studies, 210 patients). Meta-analysis of three studies indicated that the MMP-9 rs3918242 polymorphism may be associated with hemorrhagic transformation susceptibility under the dominant model (TT + CT vs. CC: OR, 0.621; 95% CI, 0.424–0.908; P = 0.014). No studies reported the association between MMP-9 rs3918242 polymorphism and brain edema or functional outcome after acute stroke.Conclusion: Our meta-analysis showed that higher MMP-9 levels were seen in stroke patients with severe brain edema and hemorrhagic transformation but not poor outcome. Circulating c-Fn levels appear to be associated with all three outcomes including severe brain edema, hemorrhagic transformation, and poor functional outcome. The C-to-T transition at the MMP-9 rs3918242 gene appears to reduce the risk of hemorrhagic transformation.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Zoe Wolcott ◽  
Ayush Batra ◽  
Jane Khoury ◽  
Matthew Sperling ◽  
Brett C Meyer ◽  
...  

Introduction: Soluble ST2 (sST2) is a member of the interleukin-1 receptor family that predicts mortality and outcome in cardiovascular disease. We aimed to determine whether baseline sST2 predicts functional outcome after stroke and examined its potential role in hemorrhagic transformation (HT). Methods: We measured plasma sST2 and matrix metalloproteinase-9 (MMP-9) in 646 patients who presented with acute ischemic stroke and were enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. Soluble ST2 and total MMP-9 were measured by ELISA. Functional outcome was assessed at 3 months with the modified Rankin Scale (mRS), with good outcome defined as mRS 0-2, and poor outcome defined as mRS 3-6. HT was classified in 246 patients with available CT scans, using the ECASS III criteria. The relationships between sST2, outcome, and HT were evaluated using multivariate logistic regression. Results: Median admission sST2 level was 35.0 ng/mL [IQR 25.7—49.8] in 646 patients (mean age 69 years; 44% women). The plasma concentration of sST2 was independently associated with poor outcome (OR 3.06, 95% CI 1.15-8.31, P =0.02) and mortality (OR 8.94, 95% CI 2.13-39.55, P =0.003) after adjustment for age, sex, NIHSS, admission glucose, cardioembolic stroke subtype, and tPA treatment. Of the 246 patients with imaging data available, HT occurred in 37 (15%) patients: 18 (48%) with hemorrhagic infarction type 1 (HI1), 11 (30%) with hemorrhagic infarction type 2 (HI2), 4 (11%) with parenchymal hemorrhage type 1 (PH1) and 4 (11%) with parenchymal hemorrhage type 2 (PH2). Admission sST2 level was associated with the subsequent development of any HT ( P =0.03) and with hemorrhagic infarction type 2 or greater (HI2, PH1, or PH2; P =0.008). Elevated sST2 independently predicted HI2 or greater after adjustment for age, MMP-9, blood glucose level, and tPA treatment (OR 9.27, 95% CI, 1.05-86.76, P =0.045). Conclusion: Plasma sST2 levels predicted mortality, functional outcome, and risk of HT after ischemic stroke. Further study of the potential link between sST2 and the brain injury response after stroke is warranted.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shuhong Yu ◽  
Yi Luo ◽  
Tan Zhang ◽  
Chenrong Huang ◽  
Yu Fu ◽  
...  

Abstract Background It has been shown that eosinophils are decreased and monocytes are elevated in patients with acute ischemic stroke (AIS), but the impact of eosinophil-to-monocyte ratio (EMR) on clinical outcomes among AIS patients remains unclear. We aimed to determine the relationship between EMR on admission and 3-month poor functional outcome in AIS patients. Methods A total of 521 consecutive patients admitted to our hospital within 24 h after onset of AIS were prospectively enrolled and categorized in terms of quartiles of EMR on admission between August 2016 and September 2018. The endpoint was the poor outcome defined as modified Rankin Scale score of 3 to 6 at month 3 after admission. Results As EMR decreased, the risk of poor outcome increased (p < 0.001). Logistic regression analysis revealed that EMR was independently associated with poor outcome after adjusting potential confounders (odds ratio, 0.09; 95% CI 0.03–0.34; p = 0.0003), which is consistent with the result of EMR (quartile) as a categorical variable (odds ratio, 0.23; 95% CI 0.10–0.52; ptrend < 0.0001). A non-linear relationship was detected between EMR and poor outcome, whose point was 0.28. Subgroup analyses further confirmed these associations. The addition of EMR to conventional risk factors improved the predictive power for poor outcome (net reclassification improvement: 2.61%, p = 0.382; integrated discrimination improvement: 2.41%, p < 0.001). Conclusions EMR on admission was independently correlated with poor outcome in AIS patients, suggesting that EMR may be a potential prognostic biomarker for AIS.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Alvaro Garcia-Tornel ◽  
Marta Olive-Gadea ◽  
Marc Ribo ◽  
David Rodriguez-Luna ◽  
Jorge Pagola ◽  
...  

A significant proportion of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) present poor functional outcome despite recanalization. We aim to investigate computed tomography perfusion (CTP) patterns after EVT and their association with outcome Methods: Prospective study of anterior large vessel occlusion AIS patients who achieved complete recanalization (defined as modified Thrombolysis in Cerebral Ischemia (TICI) 2b - 3) after EVT. CTP was performed within 30 minutes post-EVT recanalization (POST-CTP): hypoperfusion was defined as volume of time to maximal arrival of contrast (Tmax) delay ≥6 seconds in the affected territory. Hyperperfusion was defined as visual increase in cerebral blood flow (CBF) and volume (CBV) with advanced Tmax compared with the unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as a decrease of ≥8 points in NIHSS score at 24h or NIHSS≤2 and good functional outcome by mRS ≤2 at 3 months. Results: One-hundred and forty-one patients were included. 49 (34.7%) patients did not have any perfusion abnormality on POST-CTP, 60 (42.5%) showed hypoperfusion (median volume Tmax≥6s 17.5cc, IQR 6-45cc) and 32 (22.8%) hyperperfusion. DCR appeared in 56% of patients and good functional outcome in 55.3%. Post-EVT hypoperfusion was related with worse final TICI, and associated worse early clinical evolution, larger final infarct volume (p<0.01 for all) and was an independent predictor of functional outcome (OR 0.98, CI 0.97-0.99, p=0.01). Furthermore, POST-CTP identified patients with delayed improvement: in patients without DCR (n=62, 44%), there was a significant difference in post-EVT hypoperfusion volume according to functional outcome (hypoperfusion volume of 2cc in good outcome vs 11cc in poor outcome, OR 0.97 CI 0.93-0.99, p=0.04), adjusted by confounding factors. Hyperperfusion was not associated with worse outcome (p=0.45) nor symptomatic hemorrhagic transformation (p=0.55). Conclusion: Hypoperfusion volume after EVT is an accurate predictor of functional outcome. In patients without dramatic clinical recovery, hypoperfusion predicts good functional outcome and defines a “stunned-brain” pattern. POST-CTP may help to select EVT patients for additional therapies.


2019 ◽  
Vol 61 (7) ◽  
pp. 964-972 ◽  
Author(s):  
Chong Hyun Suh ◽  
Seung Chai Jung ◽  
Se Jin Cho ◽  
Dong-Cheol Woo ◽  
Woo Yong Oh ◽  
...  

Background Hemorrhagic transformation increases mortality and morbidity in patients with acute ischemic stroke. Purpose The purpose of this study is to evaluate the diagnostic performance of magnetic resonance imaging (MRI) for prediction of hemorrhagic transformation in acute ischemic stroke. Material and Methods A systematic literature search of MEDLINE and EMBASE was performed up to 27 July 2018, including the search terms “acute ischemic stroke,” “hemorrhagic transformation,” and “MRI.” Studies evaluating the diagnostic performance of MRI for prediction of hemorrhagic transformation in acute ischemic stroke were included. Diagnostic meta-analysis was conducted with a bivariate random-effects model to calculate the pooled sensitivity and specificity. Subgroup analysis was performed including studies using advanced MRI techniques including perfusion-weighted imaging, diffusion-weighted imaging, and susceptibility-weighted imaging. Results Nine original articles with 665 patients were included. Hemorrhagic transformation is associated with high permeability, hypoperfusion, low apparent diffusion coefficient (ADC), and FLAIR hyperintensity. The pooled sensitivity was 82% (95% confidence interval [CI] 61–93) and the pooled specificity was 79% (95% CI 71–85). The area under the hierarchical summary receiver operating characteristic curve was 0.85 (95% CI 0.82–0.88). Although study heterogeneity was present in both sensitivity (I2=67.96%) and specificity (I2=78.93%), a threshold effect was confirmed. Studies using advanced MRI showed sensitivity of 92% (95% CI 70–98) and specificity of 78% (95% CI 65–87) to conventional MRI. Conclusion MRI may show moderate diagnostic performance for predicting hemorrhage in acute ischemic stroke although the clinical significance of this hemorrhage is somewhat uncertain.


Sign in / Sign up

Export Citation Format

Share Document