Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome.
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ABSTRACT:
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]
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Project description:PurposeThe majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines.MethodsRetrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1-2) at 6 months.ResultsSeven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2-98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87-95% of patients). Normal S100B and NSE predicted good outcome with NPV 76-82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome.ConclusionLow levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.
| S-EPMC8421280 | biostudies-literature
Project description:ObjectiveTo test serum tau as a predictor of neurological outcome after cardiac arrest.MethodsWe measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3-5 at 6 months.ResultsIncreased tau was associated with poor outcome at 6 months after cardiac arrest (median?=?38.5, interquartile range [IQR]?=?5.7-245ng/l in poor vs median?=?1.5, IQR?=?0.7-2.4ng/l in good outcome, for tau at 72 hours, p?<?0.0001). Tau improved prediction of poor outcome compared to using clinical information (p?<?0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR?=?2% (95% CI?=?1-4%) with sensitivity?=?66% (95% CI?=?61-70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p?=?0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33?°C and 36?°C targeted temperature after cardiac arrest.InterpretationSerum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665-675.
| S-EPMC5725735 | biostudies-literature
Project description:Whether admission C-reactive protein (aCRP) concentrations are associated with neurological outcome after out-of-hospital cardiac arrest (OHCA) is controversial. Based on established kinetics of CRP, we hypothesized that aCRP may reflect the pre-arrest state of health and investigated associations with neurological outcome. Prospectively collected data from the Vienna Clinical Cardiac Arrest Registry of the Department of Emergency Medicine were analysed. Adults (≥ 18 years) who suffered a non-traumatic OHCA between January 2013 and December 2018, without return of spontaneous circulation or extracorporeal cardiopulmonary resuscitation therapy were eligible. The primary endpoint was a composite of unfavourable neurologic function or death (defined as Cerebral Performance Category 3-5) at 30 days. Associations of CRP levels drawn within 30 min of hospital admission were assessed using binary logistic regression. ACRP concentrations were overall low in our population (n = 832), but higher in the unfavourable outcome group [median: 0.44 (quartiles 0.15-1.44) mg/dL vs. 0.26 (0.11-0.62) mg/dL, p < 0.001]. The crude odds ratio for higher aCRP concentrations was 1.19 (95% CI 1.10-1.28, p < 0.001, per mg/dL) to have unfavourable neurological outcome. After multivariate adjustment for traditional prognostication markers the odds ratio of higher aCRP concentrations was 1.13 (95% CI 1.04-1.22, p = 0.002). Sensitivity of aCRP was low, but specificity for unfavourable neurological outcome was 90% for the cut-off at 1.5 mg/dL and 97.5% for 5 mg/dL CRP. In conclusion, high aCRP levels are associated with unfavourable neurological outcome at day 30 after OHCA.
| S-EPMC8119412 | biostudies-literature
Project description:ObjectivesTo assess ultra-early neuroprognostic significance of GFAP, NF-L, UCH-L1, tau, and S100B concentrations, change trajectory, and combination profile after Out-of-Hospital Cardiac Arrest (OHCA).MethodsProspective enrollment of 22 OHCA and 10 control patients at an academic tertiary care center between May 1, 2017 and January 28, 2020. Blood was collected within one hour of return of spontaneous circulation (ROSC) (H0), at hours 6 (H6), 12, 18, 24, and daily or until discharge or death. Biomarker concentrations, multifactor score, and trajectory change were assessed and compared to final neurologic status (good vs poor Cerebral Performance Category; CPC 1-2 vs CPC 3-5, respectively).Results10 patients had good and 12 had poor neurologic outcomes. Poor outcome patients had higher biomarker concentrations and combined biomarker scores at early time points. The earliest significant difference between good and poor outcome patients' serum biomarkers were at H12 for GFAP (good median: 425 pg/mL [IQR:370-630] vs poor: 5954[1712-65,055] pg/mL; p < 0.001), H12 for NF-L (64[41-69] vs 898[348-1990] pg/mL; p < 0.001), H0 for Tau (31[8-51] vs 124[53-238] pg/mL; p = 0.025), H0 for UCH-L1 (898[375-1600] vs 2475[1898-4098] pg/mL; p = 0.008), and H6 for S100B (123[70-290] vs 895[360-1199] pg/mL; p = 0.002). Four biomarker composite scores differed by H12 (78.03[52.03-111.25] vs 749 [198.46-4870.63] pg/mL; p = 0.003). Machine-learning approach also identified that four-marker score trajectory group memberships are in concordance with patient outcome.ConclusionsUltra-early serial serum concentrations of neuronal and astroglial biomarkers may be of neuroprognostic significance following OHCA.
| S-EPMC8244405 | biostudies-literature
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.
2019-03-21 | E-MTAB-7699 | biostudies-arrayexpress
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.
| S-EPMC5129173 | biostudies-literature
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.
| S-EPMC6162879 | biostudies-other
Project description:to explore the association between post return of spontaneous circulation (ROSC) hemoglobin level and survival with good neurological outcome following out-of-hospital cardiac arrest.We studied adults with non-traumatic out-of-hospital cardiac arrest who achieved ROSC within 50min of collapse. We quantified the association between post ROSC hemoglobin level and good neurological outcome (defined as Cerebral Performance Category score of 1or 2), using multivariate logistic regression analyses. The impact of Post ROSC hemoglobin level ?10gdl(-1) and time varying hemoglobin level ?10gdl(-1) on time to Survival with good outcome was assessed using Cox proportional hazard models.Of 931 cardiac arrest patients, 146 (16%) achieved ROSC and 30 survived to discharge with a good neurological outcome. Of those with post ROSC hemoglobin level ?10gdl(-1), 28% (27/98) had good outcome, whereas of those with level <10mgdl(-1) only 6% (3/48) had good outcome (CPC<3, P=0.003). The use of blood transfusions and therapeutic hypothermia were comparable in both good and bad outcome groups. An immediate post ROSC hemoglobin level ?10gdl(-1) was significantly associated with good neurological outcome (AOR 8.31 95% CI 1.89-36.52 P=0.005). Patients with post ROSC hemoglobin ?10gdl(-1) were more likely to achieve good outcome earlier (HR 6.02 95% CI 1.75-20.72 P=0.004).Post ROSC hemoglobin level ?10gdl(-1) is associated with survival with good neurological outcome. The importance of time to achieve such level and the role of blood transfusion warrants further investigation.
| S-EPMC5505771 | biostudies-literature
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) (?1), 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 (?1) 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 (?1) in predicting poor outcome was 0.84 and 0.82, respectively. In addition, the minimum value of ln VLF power or DFA (?1) 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.
| S-EPMC6798365 | biostudies-literature
Project description:(1) Background: Acute respiratory distress syndrome (ARDS) following cardiac arrest is common and associated with in-hospital mortality. We aim to investigate whether lung compliance during targeted temperature management is associated with neurological outcome in patients with ARDS after out-of-hospital cardiac arrest (OHCA). (2) Methods: This observational study is conducted in the emergency intensive care unit from January 2011 to April 2019 using data from a prospective patient registry. Adult patients (age ?18 years) who survived non-traumatic OHCA and subsequently developed ARDS based on the Berlin definition are included. Mechanical ventilator parameters such as plateau pressure, tidal volume, minute ventilation, positive end expiratory pressure, and compliance are recorded for 7 days or until death, and categorized as maximum, median, and minimum. The primary outcome is a favorable neurological outcome defined as a Cerebral Performance Category score of 1 or 2 at hospital discharge. (3) Results: Regarding 246 OHCA survivors, 119 (48.4%) patients developed ARDS. A favorable neurologic outcome was observed in 23 (19.3%). Patients with a favorable outcome have a significantly higher lung compliance (38.6 mL/cm H2O versus 27.5 mL/cm H2O), lower inspiratory pressure (12.0 cm H2O versus 16.0 cm H2O), and lower plateau pressure (17.0 cm H2O versus 21.0 cm H2O) than those with a poor neurologic outcome (all p < 0.01). Concerning time-dependent cox regression models, all maximum (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02-1.09), minimum (HR 1.08, 95% CI 1.03-1.13), and median (HR 1.06, 95% CI 1.02-1.09) compliances are independently associated with a good neurologic outcome. Maximum compliance, >32.5 mL/cm H2O at day 1, has the highest area under the receiver operating characteristic curve (0.745) with a positive predictive value of 90.4%. (4) Conclusions: Lung compliance may be an early predictor of intact neurologic survival in patients with ARDS following cardiac arrest.
| S-EPMC7073731 | biostudies-literature