BackgroundAcute Kidney Injury (AKI), a common complication of acute coronary syndromes (ACS), is associated with higher mortality and longer hospital stays. The role of cytokines and other mediators is unknown in AKI induced by an ACS (ACS-AKI), leading to several unanswered questions. The worsening of renal function is usually seen as a dichotomous phenomenon instead of a dynamic change, so evaluating changes of the renal function in time may provide valuable information in the ACS-AKI setting. The aim of this study was to explore inflammatory factors associated to de novo kidney injury induced by de novo cardiac injury secondary to ACS.MethodsOne hundred four consecutive patients with ACS were initially included on the time of admission to the Coronary Unit of the Instituto Nacional de Cardiología in Mexico City, from February to May 2016, before any invasive procedure, imaging study, diuretic or anti-platelet therapy. White blood count, hemoglobin, NT-ProBNP, troponin I, C-reactive protein, albumin, glucose, Na+, K+, blood urea nitrogen (BUN), total cholesterol, HDL, LDL, triglycerides, creatinine (Cr), endothelin-1 (ET-1), leukotriene-B4, matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinases-1, resolvin-D1 (RvD1), lipoxin-A4 (LXA4), interleukin-1β, −6, −8, and −10 were measured. We finally enrolled 78 patients, and subsequently we identified 15 patients with ACS-AKI. Correlations were obtained by a Spearman rank test. Low-rank regression, splines regressions, and also protein–protein/chemical interactions and pathways analyses networks were performed.ResultsPositive correlations of ΔCr were found with BUN, admission Cr, GRACE score, IL-1β, IL-6, NT-ProBNP and age, and negative correlations with systolic blood pressure, mean-BP, diastolic-BP and LxA4. In the regression analyses IL-10 and RvD1 had positive non-linear associations with ΔCr. ET-1 had also a positive association. Significant non-linear associations were seen with NT-proBNP, admission Cr, BUN, Na+, K+, WBC, age, body mass index, GRACE, SBP, mean-BP and Hb.ConclusionInflammation and its components play an important role in the worsening of renal function in ACS. IL-10, ET-1, IL-1β, TnI, RvD1 and LxA4 represent mediators that might be associated with ACS-AKI. IL-6, ET-1, NT-ProBNP might represent crossroads for several physiopathological pathways involved in “de novo cardiac injury leading to de novo kidney injury”.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-017-0640-0) contains supplementary material, which is available to authorized users.
Psoriasis is triggered by several stimuli that share a systemic production of interferon (IFN)-γ and other inflammatory mediators, which are key to regulate the production of matrix metalloproteinase (MMP)-9 and its inhibitor (TIMP)-1 by cells of monocytic lineage. This study evaluates the effect of the sera of 55 patients with psoriasis and 41 non-psoriatic individuals on the production of MMP-9 and TIMP-1 in cultured monocytes from a single healthy blood donor and in U937 cells. The effect of IFN-γ stimulation was also evaluated. Serum and supernatant concentrations of IFN-γ, MMP-9, and TIMP-1 were measured by enzyme-linked immunoassays, and the MMP-9/TIMP-1 ratios were calculated. In monocytes, incubation with psoriasis' sera increased the production of MMP-9 and TIMP-1 in comparison with both baseline and monocytes incubated with non-psoriatic sera. Although the MMP-9/TIMP-1 ratio was significantly higher compared to the baseline, no differences between groups were observed. In contrast, IFN-γ stimulation in monocytes previously exposed to psoriasis' sera increased MMP-9 levels and decreased TIMP-1 levels, whereas stimulation in monocytes exposed to non-psoriatic sera did not further modify the levels of MMP-9 or TIMP-1. Consequently, the MMP-9/TIMP-1 ratio in cells exposed to psoriatic serum was significantly higher than in cells exposed to non-psoriatic sera (24.5 versus 16.7; P < 0.05). Similar results were observed in U937 cells. Therefore, our results suggest that soluble mediators in psoriatic sera may enhance the proteolytic phenotype of monocytes when stimulated with IFN-γ, which supports the existence of a primed state in the inflammatory cells of patients with psoriasis.
Background: Mortality in cardiogenic shock (CS) is up to 40%, and although risk scores have been proposed to stratify and assess mortality in CS, they have been shown to have inconsistent performance. The purpose was to compare CS prognostic scores and describe their performance in a real-world Latin American country. Methods: We included 872 patients with CS. The Society for Cardiovascular Angiography and Interventions (SCAI), CARDSHOCK, IABP-Shock II, Cardiogenic Shock Score, age-lactate-creatinine score, Get-With-The-Guidelines Heart Failure score, and Acute Decompensated Heart Failure National Registry scores were calculated. Decision curve analyses were performed to evaluate the net benefit of the different scoring systems. Logistic and Cox regression analyses were applied to construct area under the curve (AUC) statistics, this last one against time using the Inverse Probability of Censoring Weighting method, for in-hospital mortality prediction. Results: When logistic regression was applied, the scores had a moderate-good performance in the overall cohort that was higher AUC in the CARDSHOCK (c = 0.666). In acute myocardial infarction-related CS (AMI-CS), CARDSHOCK still is the highest AUC (0.68). In non-AMI-CS only SCAI (0.668), CARDSHOCK (0.533), and IABP-SHOCK II (0.636) had statistically significant values. When analyzed over time, significant differences arose in the AUC, suggesting that a time-sensitive component influenced the prediction of mortality. The highest AUC was for the CARDSHOCK score (0.658), followed by SCAI (0.622). In AMI-CSrelated, the highest AUC was for the CARDSHOCK score (0.671). In non-AMI-CS, SCAI was the best (0.642). Conclusions: Clinical scores show a time-sensitive AUC, suggesting that performance could be influenced by time and the type of CS. Understanding the temporal influence on the scores could provide a better prediction and be a valuable tool in CS.
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