scholarly journals Regulatory T Cell as Predictor of Intramyocardial Hemorrhage in STEMI Patients After Primary PCI

2021 ◽  
Author(s):  
Yue Zhang ◽  
Hui Gao ◽  
Lei Liu ◽  
Shengyu Li ◽  
Bing Hua ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Regulatory T Cell ◽  
Ischemia Reperfusion ◽  
Multivariable Analysis ◽  
Left Ventricular ◽  
Baseline Risk ◽  
Marker Panel ◽  
Net Reclassification Improvement ◽  
Creatine Kinase Mb

Abstract Background: Intramyocardial hemorrhage (IMH) is a result of ischemia-reperfusion injury in ST-segment elevation myocardial infarction(STEMI) after primary percutaneous coronary intervention (PPCI). Despite patients with IMH show poorer prognoses, studies investigating predictors of IMH occurrence are scarce. This study firstly investigated the effectiveness of regulatory T cell (Treg), peak value of Creatine Kinase MB (pCKMB), high-sensitivity C-reactive protein (hsCRP), and left ventricular end-systolic diameter (LVESD) as predictors for IMH in STEMI patients received PPCI.Methods: A prospective observational cohort study was performed in STEMI patients with cardiac magnetic resonance examination 6.3±2.3 days after PPCI. Logistic regression analysis was used to screen the risk factors for IMH. The predictive ability of risk factors for IMH were determined by Receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and C-index.Results: Of the 182 patients, 80 patients (44.0%) developed IMH. On multivariable analysis, all 4 biomarkers were independent predictors of IMH [odds radio (OR) and 95% confidence interval (CI): 0.350(0.202-0.606) for Treg, 1.004(1.001-1.006) for pCKMB, 1.060(1.022-1.100) for hsCRP, and 3.329(1.346-8.236) for LVESD]. After propensity score matching, the biomarkers individually and together significantly predicted IMH with areas under the curve of 0.750 for Treg, 0.721 for pCKMB, 0.656 for hsCRP, 0.633 for LVESD, and 0.821 for the integrated 4-marker panel. The addition of integrated 4-marker panel to a baseline risk model had an incremental effect on the predictive value for IMH [NRI: 0.197 (0.039 to 0.356); IDI: 0.200 (0.142 to 0.259); C-index: 0.806 (0.744 to 0.869), all p < 0.05].Conclusions: Treg individually or in combination with pCKMB, hsCRP, and LVESD can effectively predict the existence of IMH in STEMI patients received PPCI.Name of the registry: ClinicalTrials. govTrial registration number: NCT03939338Date of registration: 6 May 2019URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03939338?term=03939338&cntry=CN&draw=2&rank=1

Lower serum retinoic acid level for prediction of higher risk of mortality in ischemic stroke

Neurology ◽  
2019 ◽  
Vol 92 (15) ◽  
pp. e1678-e1687 ◽  
Author(s):  
Wen-Jun Tu ◽  
Han-Cheng Qiu ◽  
Yiqun Zhang ◽  
Jian-lei Cao ◽  
Hong Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Retinoic Acid ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Net Reclassification Improvement ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Cvd Mortality

ObjectiveTo explore the association between serum retinoic acid (RA) level in patients with acute ischemic stroke (AIS) and mortality risk in the 6 months after admission.MethodsFrom January 2015 through December 2016, patients admitted to 3 stroke centers in China for first-ever AIS were screened. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality in the 6 months after admission. The significance of serum RA level, NIH Stroke Scale score, and established risk factors in predicting mortality were determined. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in statistical analysis.ResultsOf the 1,530 patients enrolled, 325 died within 6 months of admission, with an all-cause mortality of 21.2% and CVD-related mortality of 13.1%. In multivariable analysis, RA levels were expressed as quartiles with the clinical variables. The results of the second to fourth quartiles (Q2–Q4) were compared with the first quartile (Q1); RA levels showed prognostic significance, with decreased all-cause and CVD mortality of 55% and 63%, respectively. After RA was added to the existing risk factors, all-cause mortality could be better reclassified, in association with only the NRI statistic (p = 0.005); CVD mortality could be better reclassified with significance, in association with both the IDI and NRI statistics (p < 0.01).ConclusionsLow circulating levels of RA were associated with increased risk of all-cause and CVD mortality in a cohort of patients with first-incidence AIS, indicating that RA level could be a predictor independent of established conventional risk factors.

scholarly journals Mycophenolate mofetil modifies kidney tubular injury and Foxp3+ regulatory T cell trafficking during recovery from experimental ischemia–reperfusion

2010 ◽  
Vol 23 (1-2) ◽  
pp. 45-52 ◽  
Author(s):  
Maria Teresa Gandolfo ◽  
Hye Ryoun Jang ◽  
Serena M. Bagnasco ◽  
Gang-Jee Ko ◽  
Patricia Agreda ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
T Cell ◽  
Regulatory T Cell ◽  
Ischemia Reperfusion ◽  
Cell Trafficking ◽  
Tubular Injury ◽  
T Cell Trafficking

Abstract P014: Clinically Significant Novel Biomarkers for Prediction of First-ever Myocardial Infarction-The Tromsø Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Tom Wilsgaard ◽  
Ellisiv B Mathiesen ◽  
Henrik Schirmer ◽  
Maja-Lisa Lochen ◽  
Kaare H Bonaa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Risk Model ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Apolipoprotein A1 ◽  
Net Reclassification Improvement ◽  
Interaction Term ◽  
Clinically Significant ◽  
Traditional Risk Factors

Background: Identification of individuals with high risk for first-ever myocardial infarction (MI) can be improved. The objectives of the study ere to survey multiple protein biomarkers for association with the 5-year risk of incident MI and identify a clinically significant risk model that adds information to current common risk models. Methods: We employed an immunoassay platform that utilizes a sensitive, sample efficient molecular counting technology to measure 51 proteins in samples from the fourth survey (1994) in the Tromsø Study, a longitudinal study of men and women in Tromsø, Norway. A nested case control design was used with 182 first-ever MI cases (60 females/122 males) and 467 controls (277 females/190 males). Results: Of the proteins measured, 21 were predictors of MI before and after adjustment for traditional risk factors either in men, women or both. In stepwise multivariable analysis with these biomarkers and traditional risk factors, kallikrein; OR 0.58 (95% CI 0.47 - 0.71), matrix metalloproteinase 8; OR 1.41 (1.13 - 1.75), the interaction term CCL5/RANTES*women; OR 0.57 (0.44 - 0.74), the interaction term apolipoprotein B/apolipoprotein A1 ratio*men; OR 1.53 (1.27 - 1.84) and lipoprotein a; OR 1.33 (1.10 - 1.61) added significantly to the model with a net reclassification improvement of 0.10 (p=0.01), while the ROC area increased from 0.77 to 0.83, p<0.001. Conclusion: Novel protein biomarker models improve identification of MI risk above and beyond traditional risk factors with more than 10% better allocation to either high or low risk group than traditional risk factors alone.

scholarly journals The CXCL10/CXCR3 Axis and Cardiac Inflammation: Implications for Immunotherapy to Treat Infectious and Noninfectious Diseases of the Heart

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Raffaele Altara ◽  
Ziad Mallat ◽  
George W. Booz ◽  
Fouad A. Zouein
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Interleukin 2 ◽  
Cell Formation ◽  
Vitamin D Supplementation ◽  
Left Ventricular ◽  
Cardiac Inflammation ◽  
Promising Therapeutic Approach ◽  
Anti Inflammatory

Accumulating evidence reveals involvement of T lymphocytes and adaptive immunity in the chronic inflammation associated with infectious and noninfectious diseases of the heart, including coronary artery disease, Kawasaki disease, myocarditis, dilated cardiomyopathies, Chagas, hypertensive left ventricular (LV) hypertrophy, and nonischemic heart failure. Chemokine CXCL10 is elevated in cardiovascular diseases, along with increased cardiac infiltration of proinflammatory Th1 and cytotoxic T cells. CXCL10 is a chemoattractant for these T cells and polarizing factor for the proinflammatory phenotype. Thus, targeting the CXCL10 receptor CXCR3 is a promising therapeutic approach to treating cardiac inflammation. Due to biased signaling CXCR3 also couples to anti-inflammatory signaling and immunosuppressive regulatory T cell formation when activated by CXCL11. Numbers and functionality of regulatory T cells are reduced in patients with cardiac inflammation, supporting the utility of biased agonists or biologicals to simultaneously block the pro-inflammatory and activate the anti-inflammatory actions of CXCR3. Other immunotherapy strategies to boost regulatory T cell actions include intravenous immunoglobulin (IVIG) therapy, adoptive transfer, immunoadsorption, and low-dose interleukin-2/interleukin-2 antibody complexes. Pharmacological approaches include sphingosine 1-phosphate receptor 1 agonists and vitamin D supplementation. A combined strategy of switching CXCR3 signaling from pro- to anti-inflammatory and improving Treg functionality is predicted to synergistically lessen adverse cardiac remodeling.

scholarly journals Latent tuberculosis infection status of pregnant women in Uganda determined using QuantiFERON TB Gold-Plus

2021 ◽  
Author(s):  
Felix Bongomin ◽  
Phillip Ssekamatte ◽  
Gloria Nattabi ◽  
Ronald Olum ◽  
Sandra Ninsiima ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Hiv Infection ◽  
Pregnant Women ◽  
Smoking Status ◽  
Multivariable Analysis ◽  
Latent Tuberculosis ◽  
T Cell Responses ◽  
Preventive Therapy ◽  
Cell Responses

Abstract Background The risk of progression of latent tuberculosis (TB) infection (LTBI) to active disease increases with pregnancy. This study determined the prevalence and risk factors associated with LTBI among pregnant women in Uganda. Methods We enrolled 261 pregnant women, irrespective of gestation age. Participants who had known or suspected active TB on the basis of clinical evaluation or who had recently received treatment for TB were excluded. LTBI was defined as an interferon- gamma (IFN-γ) concentration ≥0.35 IU/mL (calculated as either TB1 (eliciting CD4 + T-cell responses) or TB2 [eliciting CD8 + T-cell responses] antigen minus nil) using QuantiFERON TB Gold-Plus (QFT-plus) assay. Results LTBI prevalence was 37.9% (n=99) (95% Confidence Interval (CI): 32.3 - 44.0). However, 24 (9.2%) subjects had indeterminate QFT-plus results. Among participants with LTBI, TB1 and TB2 alone were positive in 11 (11.1%) and 18 (18.2%) participants, respectively. In multivariable analysis, HIV-infection (adjusted odds ratio (aOR): 4.4; 95% CI: 1.1 – 18.0; p=0.04) and age group 30-39 years (aOR: 4.0; 95% CI: 1.2 – 12.7; p=0.02) were independently associated with LTBI. Meanwhile, smoking status, alcohol use, nature of residence, crowding index, and TB contact were not associated with LTBI. Conclusion Our findings are in keeping with the evidence that HIV infection and advancing age are important risk factors for LTBI in pregnancy. In our setting, we recommend routine screening for LTBI and TB preventive therapy among eligible pregnant women.

scholarly journals Mycobacterium tuberculosis infection, immune activation, and risk of HIV acquisition

2021 ◽  
Author(s):  
Rachel A. Bender Ignacio ◽  
Jessica Long ◽  
Aparajita Saha ◽  
Felicia K. Nguyen ◽  
Lara Joudeh ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
T Cell Activation ◽  
Hiv Risk ◽  
Immune Activation ◽  
Conditional Logistic Regression ◽  
Intracellular Cytokine Staining ◽  
Multivariable Analysis ◽  
Cd4 T Cell ◽  
Hiv Acquisition

AbstractBackgroundAlthough immune activation is associated with HIV acquisition, the nature of inflammatory profiles that increase HIV risk, which may include responses to M. tuberculosis (Mtb) infection, are not well characterized.MethodsWe conducted a nested case-control study within the Step MRKAd5 HIV-1 vaccine study. PBMCs from the last HIV-negative sample from incident HIV cases and controls who did not acquire HIV were stimulated with Mtb-specific antigens (ESAT-6/CFP-10) and analyzed by flow cytometry with intracellular cytokine staining.Combinatorial polyfunctionality analysis of antigen-specific T-cell subsets (COMPASS) determined overall Mtb-antigen-specific T cell activation. We measured inflammatory profiles with five Correlates of TB Risk (CoR) peripheral blood transcriptomic signatures. Conditional logistic regression analyses, adjusted for known predictors of HIV acquisition, were employed to assess whether either cellular markers of TB-associated immune activation or transcriptomic predictors of TB disease states were associated with HIV acquisition.ResultsAmong 465 participants, latent Mtb infection (LTBI) prevalence (21.5% controls vs 19.1% cases, p=0.51) and Mtb antigen-specific polyfunctional CD4+ T cell COMPASS scores (aOR 0.96, 95% CI 0.77, 1.20) were not higher in those who acquired HIV. Two CoR signatures, Sweeney3 (aOR 1.38 (1.07, 1.78) per SD change) and RESPONSE5 (0.76 (0.60, 0.95)), were associated with HIV acquisition in multivariable analysis. The Sweeney3 signature best predicted odds of acquiring HIV in unadjusted and adjusted analyses, including when restricted to LTBI-negative participants.ConclusionsLTBI and Mtb polyfunctional antigen-specific CD4+ T cell immune activation were not identified as risk factors for HIV acquisition, but transcriptomic analyses demonstrated that two CoR signatures predicted HIV risk after adjustment for known behavioral and clinical risk factors. CoR signatures can demonstrate host gene expression associated with HIV acquisition, but the observed effects are likely not mediated through Mtb infection.

scholarly journals Impact of cardiovascular risk factors on myocardial work—insights from the STAAB cohort study

2021 ◽  
Author(s):  
Floran Sahiti ◽  
Caroline Morbach ◽  
Vladimir Cejka ◽  
Theresa Tiffe ◽  
Martin Wagner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Multivariable Analysis ◽  
Left Ventricular ◽  
Ventricular Performance ◽  
Work Index ◽  
Constructive Work ◽  
Volume Measurements ◽  
And Gender ◽  
Global Work

AbstractMyocardial work is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure–strain loops, and has been validated against invasively derived pressure–volume measurements. Myocardial work is described by its components (global constructive work [GCW], global wasted work [GWW]) and indices (global work index [GWI], global work efficiency [GWE]). Applying this innovative concept, we characterized the prevalence and severity of subclinical left ventricular compromise in the general population and estimated its association with cardiovascular (CV) risk factors. Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study we comprehensively phenotyped a representative sample of the population of Würzburg, Germany, aged 30–79 years. Indices of myocardial work were determined in 1929 individuals (49.3% female, mean age 54 ± 12 years). In multivariable analysis, hypertension was associated with a mild increase in GCW, but a profound increase in GWW, resulting in higher GWI and lower GWE. All other CV risk factors were associated with lower GCW and GWI, but not with GWW. The association of hypertension and obesity with GWI was stronger in women. We conclude that traditional CV risk factors impact selectively and gender-specifically on left ventricular myocardial performance, independent of systolic blood pressure. Quantifying active systolic and diastolic compromise by derivation of myocardial work advances our understanding of pathophysiological processes in health and cardiac disease.

Abstract TP417: Plasma D-dimer Elevation Predicts Poor Functional Outcomes Through Systemic Complications After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hitoshi Fukuda ◽  
Yu Yamamoto ◽  
Akira Handa ◽  
Yoshitaka Kurosaki ◽  
Sen Yamagata
Keyword(s):  
Risk Factors ◽  
Subarachnoid Hemorrhage ◽  
Functional Outcomes ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariable Analysis ◽  
Neurological Complications ◽  
Systemic Complications ◽  
Net Reclassification Improvement ◽  
Conventional Risk Factors ◽  
D Dimer

Introduction: Plasma D-dimer levels elevate during acute stage of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. Hypothesis: We hypothesize that D-dimer levels on admission are correlated with systemic complications rather than neurological complications, and therefore have an additive predictive value on conventional risk factors for poor functional outcomes. Methods: A total of 187 patients with aneurymal SAH were retrospectively analyzed from a single center, observational cohort database. Correlations of plasma D-dimer levels on admission with patients’ characteristics, initial presentation, neurological complications, and systemic complications were identified. We also evaluated additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer. Result and Conclusions: D-dimer elevation on admission was associated with increasing age, women, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07-1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01-1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04-1.37], p = 0.01) by multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcomes (modified Rankin scale 3-6, OR 1.50 [95% CI 1.15-1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer, evaluated by C statistics, net reclassification improvement, and integrated discrimination improvement methods. These results suggest that elevated D-dimer levels on admission were independently correlated with systemic complications, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.

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