Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C.
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ABSTRACT:
SUBMITTER: Stammet P
PROVIDER: S-EPMC5477102 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C.
Stammet Pascal P Dankiewicz Josef J Nielsen Niklas N Fays François F Collignon Olivier O Hassager Christian C Wanscher Michael M Undèn Johan J Wetterslev Jorn J Pellis Tommaso T Aneman Anders A Hovdenes Jan J Wise Matt P MP Gilson Georges G Erlinge David D Horn Janneke J Cronberg Tobias T Kuiper Michael M Kjaergaard Jesper J Gasche Yvan Y Devaux Yvan Y Friberg Hans H
Critical care (London, England) 20170620 1
<h4>Background</h4>We aimed to investigate the diagnostic performance of S100 as an outcome predictor after out-of-hospital cardiac arrest (OHCA) and the potential influence of two target temperatures (33 °C and 36 °C) on serum levels of S100.<h4>Methods</h4>This is a substudy of the Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial. Serum levels of S100 were measured a posteriori in a core laboratory in samples collected at 24, 48, and 72 h after OHCA. Outcome at 6 ...[more]
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Project description:Purpose: To evaluate serum S100 protein at hospital admission and after 48 h in early neuroprognostication of comatose survivors of out-of-hospital cardiac arrest (OHCA). Methods: The study included 48 consecutive patients after OHCA, who survived for at least 72 h after the event. The patients were divided based on their best cerebral performance category (CPC) achieved over a 30 day follow-up period: favorable neurological outcome (CPC 1-2) vs. unfavorable neurological outcome (CPC 3-4). Predictors of an unfavorable neurological outcome were identified by multivariable regression analysis. Analysis of the receiver operating characteristic curve (ROC) was used to determine the cut-off value for S100, having a 0% false-positive prediction rate. Results: Of the 48 patients, 30 (63%) had a favorable and 18 (38%) had an unfavorable neurological outcome. Eleven patients (23%) died over the 30 day follow-up. Increased S100 levels at 48 h after OHCA, but not the baseline S100 levels, were independently associated with unfavorable neurological outcome, with an area under the ROC curve of 0.85 (confidence interval 0.74-0.96). A 48 h S100 value ≥0.37 μg/L had a specificity of 100% and sensitivity of 39% in predicting an unfavorable 30 day neurological outcome. Conclusion: This study showed that S100 values assessed 48 h after an OHCA could independently predict an unfavorable neurological outcome at 30 days.
| S-EPMC7900190 | biostudies-literature
Project description:This study aimed to investigate the utility of quantitative EEG biomarkers for predicting good neurologic outcomes in OHCA survivors treated with targeted temperature management (TTM) using power spectral density (PSD), event-related spectral perturbation (ERSP), and spectral entropy (SE). This observational registry-based study was conducted at a tertiary care hospital in Korea using data of adult nontraumatic comatose OHCA survivors who underwent standard EEG and treated with TTM between 2010 and 2018. Good neurological outcome at 1 month (Cerebral Performance Category scores 1 and 2) was the primary outcome. The linear mixed model analysis was performed for PSD, ESRP, and SE values of all and each frequency band. Thirteen of the 54 comatose OHCA survivors with TTM and EEG were excluded due to poor EEG quality or periodic/rhythmic pattern, and EEG data of 41 patients were used for analysis. The median time to EEG was 21 h, and the rate of the good neurologic outcome at 1 month was 52.5%. The good neurologic outcome group was significantly younger and showed higher PSD and ERSP and lower SE features for each frequency than the poor outcome group. After age adjustment, only the alpha-PSD was significantly higher in the good neurologic outcome group (1.13 ± 1.11 vs. 0.09 ± 0.09, p = 0.031) and had best performance with 0.903 of the area under the curve for predicting good neurologic outcome. Alpha-PSD best predicts good neurologic outcome in OHCA survivors and is an early biomarker for prognostication. Larger studies are needed to conclusively confirm these findings.
| S-EPMC9240023 | biostudies-literature
Project description:This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.
2023-10-24 | PXD040592 | Pride
Project description:ImportanceInternational resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.ObjectiveTo determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM.Design, setting, and participantsThis was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016.InterventionsPatients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C.Main outcomes and measuresThe primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use.ResultsIn 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group.Conclusions and relevanceIn unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted.Trial registrationclinicaltrials.gov Identifier: NCT01689077.
| S-EPMC5541324 | biostudies-literature
Project description:ImportanceIt is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest.ObjectiveTo examine whether illness severity is associated with changes in the association between target temperature and patient outcome.Design, setting, and participantsThis cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation.ExposureTTM at 36 °C or 33 °C.Main outcomes and measuresPrimary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category.ResultsAmong 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, -13.8%; 95% CI, -24.4% to -3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies.Conclusions and relevanceIn this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.
| S-EPMC7378753 | 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:Patients resuscitated after cardiac arrest are reportedly at high risk for infection and sepsis, especially those treated with targeted temperature management (TTM). There is, however, limited evidence suggesting that early antibiotic use improves patient outcomes. We examined the hypothesis that early treatment with antibiotics reduces mortality in patients with cardiac arrest receiving TTM.We identified 2803 patients with cardiogenic out-of-hospital cardiac arrest (OHCA) that were treated with TTM and were admitted to 371 hospitals that contribute to the Japanese Diagnosis Procedure Combination inpatient database between July 2007 and March 2013. Of these, 1272 received antibiotics within the first 2 days (antibiotics) and 1531 did not (control). We generated 802 propensity score-matched pairs.There was no significant difference in 30-day mortality between the groups (control vs. antibiotics; 33.0 % vs. 29.9 %; difference, 3.1 %; 95 % confidence interval [CI], -1.4 to 7.7 %, p = 0.18). Analysis using the hospital antibiotics prescribing rate as an instrumental variable showed that antibiotic use was not significantly associated with a reduction in 30-day mortality (6.6 %, CI 95 %, -0.5 to 13.7 %, p = 0.28). A subgroup analysis of patients who required extracorporeal membrane oxygenation (ECMO) indicated a significant difference in 30-day mortality between the 2 groups (62.9 % vs. 43.5 %; difference 19.3 %, CI 95 %, 5.9 to 32.7 %, p = 0.005). In the instrumental variable model, the estimated reduction in 30-day mortality associated with antibiotics was 18.2 % (CI 95 %, 21.3 to 34.4 %, p = 0.03) in ECMO patients.Although there was no significant association between the use of antibiotics and mortality after overall cardiogenic OHCA treated with TTM, antibiotics may be beneficial in patients who require ECMO.
| S-EPMC5055699 | biostudies-other
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:Several studies have estimated the associations between extreme temperatures and mortality and morbidity; however, few have investigated the attributable fraction for a wide range of temperatures on the risk of out-of-hospital cardiac arrest (OHCA). We obtained daily records of OHCA cases in the 47 Japanese prefectures between 2005 and 2014. We examined the relationship between OHCA and temperature for each prefecture using a Poisson regression model combined with a distributed lag non-linear model. The estimated prefecture-specific associations were pooled at the nationwide level using a multivariate random-effect meta-analysis. A total of 659,752 cases of OHCA of presumed-cardiac origin met the inclusion criteria. Overall, 23.93% (95% empirical confidence interval [eCI]: 20.15-26.19) of OHCA was attributable to temperature. The attributable fraction to low temperatures was 23.64% (95% eCI: 19.76-25.87), whereas that of high temperatures was 0.29% (95% eCI: 0.21-0.35). The attributable fraction for OHCA was related to moderate low temperature with an overall estimate of 21.86% (95% eCI: 18.10-24.21). Extreme temperatures were responsible for a small fraction. The majority of temperature-related OHCAs were attributable to lower temperatures. The attributable risk of extremely low and high temperatures was markedly lower than that of moderate temperatures.
| S-EPMC5206734 | biostudies-literature
Project description:BACKGROUND:This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. METHODS:This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24?months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24?months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7?months, using sensitivity and specificity analyses. DISCUSSION:In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03543371 . Registered 1 June 2018.
| S-EPMC7542852 | biostudies-literature