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Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest.

ABSTRACT: BACKGROUND:Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA). METHODS:Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed. RESULTS:Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3-5). Patients with CPC 3-5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1-20.4] ng/mL) compared to those with CPC 1-2 (7.6 [IQR, 4.1-13.1] ng/mL; p?=?0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01-1.17; p?=?0.020), home setting arrest (OR, 8.07; 95% CI 1.61-40.42; p?=?0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84-34.01; p?=?0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32-10.60; p?=?0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (??10.8 vs.?

SUBMITTER: Rueda F

PROVIDER: S-EPMC6797678 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest.

Rueda Ferran F Cediel Germán G García-García Cosme C Aranyó Júlia J González-Lopera Marta M Aranda Nevado M Cruz MC Serra Gregori Judith J Oliveras Teresa T Labata Carlos C Ferrer Marc M El Ouaddi Nabil N Bayés-Genís Antoni A

Annals of intensive care 20191017 1

<h4>Background</h4>Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA).<h4>Methods</h4>Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university cente ...[more]

PMID: 31624933

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Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.

Project description:Background. Out-of-hospital cardiac arrest (OHCA) remains a challenge for emergency physicians, given the poor prognosis. In 2020, MIRACLE2, a new and easier to apply score, was established to predict the neurological outcome of OHCA. Objective. The aim of this study is to compare the discrimination of MIRACLE2 score with cardiac arrest hospital prognosis (CAHP) score for OHCA neurologic outcomes. Methods. This retrospective cohort study was conducted between January 2015 and December 2019. Adult patients (>17 years) with cardiac arrest who were brought to the hospital by an emergency medical service crew were included. Deaths due to trauma, burn, drowning, resuscitation not initiated due to pre-ordered “do not resuscitate” orders, and patients who did not achieve return of spontaneous circulation were excluded. Receiver operating characteristic curve analysis with Youden Index was performed to calculate optimal cut-off values for both scores. Results. Overall, 200 adult OHCA cases were analyzed. The threshold of the MIRACLE2 score for favorable neurologic outcomes was 5.5, with an area under the curve (AUC) value of 0.70 (0.61−0.80, p < 0.001); the threshold of the CAHP score was 223.4, with an AUC of 0.77 (0.68−0.86, p < 0.001). On setting the MIRACLE2 score cut-off value, we documented 64.7% sensitivity (95% confidence interval [CI], 56.9−71.9%), 66.7.0% specificity (95% CI, 48.2−82.0%), 90.8% positive predictive value (PPV; 95% CI, 85.6−94.2%), and 27.2% negative predictive value (NPV; 95% CI, 21.4−33.9%). On establishing a CAHP cut-off value, we observed 68.2% sensitivity (95% CI, 60.2−75.5%), 80.6% specificity (95% CI, 62.5−92.6%), 94.6% PPV (95% CI, 88.6%−98.0%), and 33.8% NPV (95% CI, 23.2−45.7%) for unfavorable neurologic outcomes. Conclusions. The CAHP score demonstrated better discrimination than the MIRACLE2 score, affording superior sensitivity, specificity, PPV, and NPV; however, the CAHP score remains relatively difficult to apply. Further studies are warranted to establish scores with better discrimination and ease of application.

Project description:Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1-2 as good and 3-5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter-quartile range, IQR) FGF 21 concentration was 0.25 (0.094-0.91) ng/ml in controls, 0.79 (0.37-1.6) ng/ml in patients at ICU admission (P < 0.001 compared to controls) and peaked at 48 h [1.2 (0.46-2.5) ng/ml]. We found no association between arterial blood oxygen partial pressure and FGF 21 concentrations. We observed with linear modeling an effect of sample timepoint (F 5.6, P < 0.01), poor neurological outcome (F 6.1, P = 0.01), and their interaction (F 3.0, P = 0.03), on FGF 21 concentration. In multivariate logistic regression analysis, adjusting for relevant clinical covariates, higher average FGF 21 concentration during the first 72 h was independently associated with poor neurological outcome (odds ratio 1.60, 95% confidence interval 1.10-2.32). We conclude that post cardiac arrest patients experience cellular and mitochondrial stress, reflected as a systemic FGF 21 response. This response is higher with a more severe hypoxic injury but it is not exacerbated by hyperoxia.

Project description:In a departure from the previous strategy of immediate defibrillation, the 2005 resuscitation guidelines from the American Heart Association-International Liaison Committee on Resuscitation suggested that emergency medical service (EMS) personnel could provide 2 minutes of cardiopulmonary resuscitation (CPR) before the first analysis of cardiac rhythm. We compared the strategy of a brief period of CPR with early analysis of rhythm with the strategy of a longer period of CPR with delayed analysis of rhythm.We conducted a cluster-randomized trial involving adults with out-of-hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the United States and Canada. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of ?3, on a scale of 0 to 6, with higher scores indicating greater disability).We included 9933 patients, of whom 5290 were assigned to early analysis of cardiac rhythm and 4643 to later analysis. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome, with a cluster-adjusted difference of -0.2 percentage points (95% confidence interval, -1.1 to 0.7; P=0.59). Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, also showed no survival benefit for either study group.Among patients who had an out-of-hospital cardiac arrest, we found no difference in the outcomes with a brief period, as compared with a longer period, of EMS-administered CPR before the first analysis of cardiac rhythm. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.).

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Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest.

Publications

Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest.

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