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Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome.

ABSTRACT: 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?

SUBMITTER: Pekkarinen PT

PROVIDER: S-EPMC7804444 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome.

Pekkarinen Pirkka T PT Skrifvars Markus B MB Lievonen Ville V Jakkula Pekka P Albrecht Laura L Loisa Pekka P Tiainen Marjaana M Pettilä Ville V Reinikainen Matti M Hästbacka Johanna J

Scientific reports 20210112 1

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 mana ...[more]

PMID: 33436812

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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:To analyze functional performance measures collected prospectively during the conduct of a clinical trial that enrolled children (up to age 18 yr old), resuscitated after out-of-hospital cardiac arrest, who were at high risk of poor outcomes.Children with Glasgow Motor Scale score less than 5, within 6 hours of resuscitation, were enrolled in a clinical trial that compared two targeted temperature management interventions (THAPCA-OH, NCT00878644). The primary outcome, 12-month survival with Vineland Adaptive Behavior Scale, second edition, score greater or equal to 70, did not differ between groups.Thirty-eight North American PICUs.Two hundred ninety-five children were enrolled; 270 of 295 had baseline Vineland Adaptive Behavior Scale, second edition, scores greater or equal to 70; 87 of 270 survived 1 year.Targeted temperatures were 33.0°C and 36.8°C for hypothermia and normothermia groups.Baseline measures included Vineland Adaptive Behavior Scale, second edition, Pediatric Cerebral Performance Category, and Pediatric Overall Performance Category. Pediatric Cerebral Performance Category and Pediatric Overall Performance Category were rescored at hospital discharges; all three were scored at 3 and 12 months. In survivors with baseline Vineland Adaptive Behavior Scale, second edition scores greater or equal to 70, we evaluated relationships of hospital discharge Pediatric Cerebral Performance Category with 3- and 12-month scores and between 3- and 12-month Vineland Adaptive Behavior Scale, second edition, scores. Hospital discharge Pediatric Cerebral Performance Category scores strongly predicted 3- and 12-month Pediatric Cerebral Performance Category (r = 0.82 and 0.79; p < 0.0001) and Vineland Adaptive Behavior Scale, second edition, scores (r = -0.81 and -0.77; p < 0.0001). Three-month Vineland Adaptive Behavior Scale, second edition, scores strongly predicted 12-month performance (r = 0.95; p < 0.0001). Hypothermia treatment did not alter these relationships.In comatose children, with Glasgow Motor Scale score less than 5 in the initial hours after out-of-hospital cardiac arrest resuscitation, function scores at hospital discharge and at 3 months predicted 12-month performance well in the majority of survivors.

Project description:BACKGROUND:The prognosis in refractory out-of-hospital cardiac arrest (OHCA) with ongoing cardiopulmonary resuscitation (CPR) at hospital arrival is often considered dismal. The use of extracorporeal cardiopulmonary resuscitation (eCPR) for perfusion enhancement during resuscitation has shown variable results. We aimed to investigate outcome in refractory OHCA patients managed conservatively without use of eCPR. METHODS:We included consecutive OHCA patients with refractory arrest or prehospital return of spontaneous circulation (ROSC) in the Copenhagen area in 2002-2011. RESULTS:A total of 3992 OHCA patients with resuscitation attempts were included; in 2599, treatment was terminated prehospital, and 1393 (35%) were brought to the hospital either with ROSC (n?=?1285, 92%) or with refractory OHCA (n?=?108, 8%). Of patients brought in with refractory OHCA, 56 (52%) achieved ROSC in the emergency department. There were no differences between patients with refractory OHCA or prehospital ROSC with regard to age, sex, comorbidities, or etiology of OHCA. Time to emergency medical services (EMS) arrival was similar, whereas time to ROSC (when ROSC was achieved) was longer in refractory OHCA patients (EMS, 6 (5-9] vs. 7 [5-10] min, p?=?0.8; ROSC, 15 [9-22] vs. 27 [20-41] min, p?<?0.001). Independent factors associated with transport with refractory OHCA instead of prehospital termination of therapy were OHCA in public (OR, 3.6 [95% CI, 2.2-5.8]; p?<?0.001), witnessed OHCA (OR, 3.7 [2.0-7.1]; p?<?0.001), shockable rhythm (OR, 3.0 [1.9-4.7]; p?<?0.001), younger age (OR, 1.2 [1.1-1.2]; p?<?0.001), and later calendar year (OR, 1.4 [1.2-1.6]; p?<?0.001). Thirty-day survival was 20% in patients with refractory OHCA compared with 42% in patients with prehospital ROSC (p?<?0.001). Four of 28 refractory OHCA patients with duration of resuscitation >?60 min achieved ROSC. No difference in favorable neurological outcome in patients surviving to discharge was found (prehospital ROSC 84% vs. refractory OHCA 86%; p?=?0.7). CONCLUSIONS:Survival after refractory OHCA with ongoing CPR at hospital arrival was significantly lower than among patients with prehospital ROSC. Despite a lower survival, the majority of survivors with both refractory OHCA and prehospital ROSC were discharged with a similar degree of favorable neurological outcome, indicating that continued efforts in spite of refractory OHCA are not in vain and may still lead to favorable outcome even without eCPR.

Project description:BACKGROUND:Most deaths of comatose survivors of out-of-hospital sudden cardiac arrest result from withdrawal of life-sustaining treatment (WLST) decisions based on poor neurological prognostication and the family's intention. Thus, accurate prognostication is crucial to avoid premature WLST decisions. However, targeted temperature management (TTM) with sedation or neuromuscular blockade against shivering significantly affects early prognostication. In this study, we investigated whether heart rate variability (HRV) analysis could prognosticate poor neurological outcome in comatose patients undergoing hypothermic TTM. METHODS:Between January 2015 and December 2017, adult patients with out-of-hospital sudden cardiac arrest, successfully resuscitated in the emergency department and admitted to the intensive care unit of the Niigata University in Japan, were prospectively included. All patients had an initial Glasgow Coma Scale motor score of 1 and received hypothermic TTM (at 34 °C). Twenty HRV-related variables (deceleration capacity; 4 time-, 3 geometric-, and 7 frequency-domain; and 5 complexity variables) were computed based on RR intervals between 0:00 and 8:00 am within 24 h after return of spontaneous circulation (ROSC). Based on Glasgow Outcome Scale (GOS) at 2 weeks after ROSC, patients were divided into good outcome (GOS 1-2) and poor outcome (GOS 3-5) groups. RESULTS:Seventy-six patients were recruited and allocated to the good (n = 22) or poor (n = 54) outcome groups. Of the 20 HRV-related variables, ln very-low frequency (ln VLF) power, detrended fluctuation analysis (DFA) (α1), and multiscale entropy (MSE) index significantly differed between the groups (p = 0.001), with a statistically significant odds ratio (OR) by univariate logistic regression analysis (p = 0.001). Multivariate logistic regression analysis of the 3 variables identified ln VLF power and DFA (α1) as significant predictors for poor outcome (OR = 0.436, p = 0.006 and OR = 0.709, p = 0.024, respectively). The area under the receiver operating characteristic curve for ln VLF power and DFA (α1) in predicting poor outcome was 0.84 and 0.82, respectively. In addition, the minimum value of ln VLF power or DFA (α1) for the good outcome group predicted poor outcome with sensitivity = 61% and specificity = 100%. CONCLUSIONS:The present data indicate that HRV analysis could be useful for prognostication for comatose patients during hypothermic TTM.

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Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome.

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Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome.

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