Combining NSE and S100B with clinical examination findings to predict survival after resuscitation from cardiac arrest.
ABSTRACT: Neuron specific enolase (NSE) and astroglial protein S100B are associated with outcome following resuscitation from cardiac arrest. We tested whether NSE and S100B levels are associated with illness severity on hospital arrival, and whether levels are independently associated with survival to hospital discharge after adjusting for initial illness severity.Levels of NSE and S100B were obtained at arrival, 6, 12, 24, 48, and 72h after successful resuscitation from cardiac arrest. Clinical data included demographics, Pittsburgh Cardiac Arrest Category (PCAC I-IV) and survival to hospital discharge. Univariable and multivariable predictive models including NSE and S-100B were created to predict survival. ROC analyses were performed to determine sensitivity and specificity of NSE and S-100B at each time interval.Of 77 comatose subjects, 5 did not receive therapeutic hypothermia and were excluded. Mean age was 59 (SD 16) years, with 58% male (N=42), 72% out-of-hospital arrest (N=52), and 43% VF/VT. Survival was 36% (N=26). PCAC IV was associated with higher levels of NSE at 24h (p=0.001) and S100B at 24h (p=0.005). In the multivariate analysis, survival was associated with initial S100B level (OR 0.24; 95% CI 0.07-0.86). NSE values>49.5ng/mL at 48h and NSE values>10.59ng/mL at 72h predicted mortality. S100B levels>0.414ng/mL at 72h predicted mortality.More severe neurologic injury on initial examination is associated with higher levels of NSE and S100B. Elevated levels of S100B immediately following resuscitation were associated with death. Persistently elevated levels of NSE and S100B at 48 and 72h were associated with death.
Project description:AIM:The aim of our study was to evaluate the potential role of resistin in estimating the 30 days prognosis in patients with hypoxic-ischemic organ injury who survived after a cardiac arrest (CA). MATERIALS AND METHODS:The study included 40 patients resuscitated after a non-traumatic out-of-hospital CA admitted in Emergency Department (ED). All patients were followed for 30 days after CA or until death. Clinical data on admission were recorded. Blood samples were collected on admission in ED (0-time interval), and at 6, 12, 24, 48- and 72-hours following resuscitation. Serum concentrations of resistin, S100B and neuron specific enolase (NSE) were measured. Several predictive scores for the mortality at 30 days were created with logistic regressions. RESULTS:At each time interval, median serum levels of resistin and S100 B were significantly higher in non-survivors compared to survivors. For NSE, plasma levels were significantly lower in survivors as compared to non-survivors at 48 and 72 hours, respectively. Accurate predictive scores for 30-days mortality were the ones which included the values of resistin and S100B measured at 12 hours after admittance [AUC 0.938 (0.813-0.989), sensitivity 85.71% (67.3%- 96%), specificity 91.67% (61.5%'99.8%), p<0.001], which included the values of all three markers measured at 12 hours after admittance [AUC 0.955 (0.839-0.995), sensitivity 82.14% (63.1%'93.9%), specificity 100.00% (73.5%'100.0%), p<0.001] and the that included the values of resistin and S-100B at 6 hours together with serum lactate on admission [AUC = 0.994 (0.901-1.0), sensitivity 96.4% (81.7%'99.9%), specificity 100.00% (73.5%'100.0%), p<0.001]. CONCLUSION:In our study, serum levels of resistin or a combination of resistin with S-100B or resistin with S-100B and lactate, were highly predictive for 30 days mortality in resuscitated patients after CA. Further studies on large number of patients are needed to confirm our data.
Project description:Mitochondrial dysfunction contributes to brain injury following global cerebral ischemia after cardiac arrest. Carbon monoxide treatment has shown potent cytoprotective effects in ischemia/reperfusion injury. This study aimed to investigate the effects of carbon monoxide-releasing molecules on brain mitochondrial dysfunction and brain injury following resuscitation after cardiac arrest in rats. A rat model of cardiac arrest was established by asphyxia. The animals were randomly divided into the following 3 groups: cardiac arrest and resuscitation group, cardiac arrest and resuscitation plus carbon monoxide intervention group, and sham control group (no cardiac arrest). After the return of spontaneous circulation, neurologic deficit scores (NDS) and S-100B levels were significantly decreased at 24, 48, and 72 h, but carbon monoxide treatment improved the NDS and S-100B levels at 24 h and the 3-day survival rates of the rats. This treatment also decreased the number of damaged neurons in the hippocampus CA1 area and increased the brain mitochondrial activity. In addition, it increased mitochondrial biogenesis by increasing the expression of biogenesis factors including peroxisome proliferator-activated receptor-? coactivator-1?, nuclear respiratory factor-1, nuclear respiratory factor-2 and mitochondrial transcription factor A. Thus, this study showed that carbon monoxide treatment alleviated brain injury after cardiac arrest in rats by increased brain mitochondrial biogenesis.
Project description:PURPOSE:We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury. METHODS:In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 23 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65-75 mmHg) vs. high-normal (80-100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest. RESULTS:We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p?<?0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2-34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6-30.9 µg/L) in the high-normal MAP group, p?=?0.522. We found no differences in the secondary outcomes. CONCLUSIONS:Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.
Project description:This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30?minutes.The ROSC (n?=?26) and non-ROSC (n?=?26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0-2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07-0.94, P?=?0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93-0.99, P?=?0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r?=?0.31, P?=?0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.
Project description:The purpose of this study was to validate the ability of an early post-cardiac arrest illness severity classification to predict patient outcomes.The Pittsburgh Cardiac Arrest Category (PCAC) is a 4-level illness severity score that was found to be strongly predictive of outcomes in the initial derivation study. We assigned PCAC scores to consecutive in and out-of-hospital cardiac arrest subjects treated at two tertiary care centers between January 2011 and September 2013. We made assignments prospectively at Site 1 and retrospectively at Site 2. Our primary outcome was survival to hospital discharge. Inter-rater reliability of retrospective PCAC assessments was assessed. Secondary outcomes were favorable discharge disposition (home or acute rehabilitation), Cerebral Performance Category (CPC) and modified Rankin Scale (mRS) at hospital discharge. We tested the association of PCAC with each outcome using unadjusted and multivariable logistic regression.We included 607 cardiac arrest patients during the study (393 at Site 1 and 214 at Site 2). Site populations differed in age, arrest location, rhythm, use of hypothermia and distribution of PCAC. Inter-rater reliability of retrospective PCAC assignments was excellent (?=0.81). PCAC was associated with survival (unadjusted odds ratio (OR) for Site 1: 0.33 (95% confidence interval (CI) 0.27-0.41)) Site 2: 0.32 (95% CI 0.24-0.43) even after adjustment for other clinical variables (adjusted OR Site 1: 0.32 (95% CI 0.25-0.41) Site 2: 0.31 (95% CI 0.22-0.44)). PCAC was predictive of secondary outcomes.Our results confirm that PCAC is strongly predictive of survival and good functional outcome after cardiac arrest.
Project description:Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation; however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline (control) or 1 × 106 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-?, interferon-?, macrophage inflammatory protein-1?, macrophage inflammatory protein-2, macrophage inflammatory protein-3?, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ? 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ? 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016 (approval No. 2016079).
Project description:<h4>Background and aim</h4>Hypoxic-ischemic encephalopathy (HIE) is a disorder featured by hypoxic and ischemic damages during the perinatal period and its high mortality (i.e., 15%-20%) could be partly attributed to late diagnosis. Therefore, miR-210 and miR-374a were investigated to find if they could improve the diagnostic values of S100B protein and neuron-specific enolase (NSE) for HIE.<h4>Methods</h4>Altogether 167 HIE newborns and 82 healthy newborns were recruited, and their blood were sampled for determining the levels of biomarkers. Specifically, S100B protein and NSE levels were detected based on the enzyme-linked immunosorbent assay (ELISA) kit, while the expressions of miR-210 and miR-374a were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, the receiver operating characteristic (ROC) curves were established to assess the diagnostic values of the above biomarkers for HIE. Finally, the correlation analysis between miR-210/miR-374 and Neonatal Behavioral Neurological Assessment (NBNA) scoring or Gesell intellectual development were also conducted.<h4>Results</h4>The levels of miR-210, miR-374a, S100B protein, and NSE were significantly distinct between HIE patients and healthy newborns (<i>p </i><<i> </i>.05). Besides, miR-210 (<i>r</i><sub>s</sub> = .573), miR-374a (<i>r</i><sub>s</sub> = .651), NSE level (<i>r</i><sub>s</sub> = -.622), and S100B level (<i>r</i><sub>s</sub> = -.55) were all, respectively, correlated with NBNA scoring with statistical significance (<i>p </i><<i> </i>.05). Furthermore, it was revealed that the combined diagnosis of miR-210, miR-374a, S100B protein, and NSE could obtain the highest accuracy regarding pairs of mild HIE versus moderate HIE (AUC = 0.898), moderate HIE versus severe HIE (AUC = 0.922), mild HIE versus severe HIE (AUC = 0.996), and HIE versus control (AUC = 0.960). More than that, the four molecules were also remarkably associated with Gesell intellectual development (<i>p </i><<i> </i>.05).<h4>Conclusion</h4>MiR-210 and miR-374a could help to elevate the diagnostic value and prognostic prediction of S100B protein and NSE for HIE.
Project description:BACKGROUND: Mild therapeutic hypothermia alters the validity of a number of parameters currently used to predict neurological outcome after cardiac arrest and resuscitation. Thus, additional parameters are needed to increase certainty of early prognosis in these patients. A promising new approach is the determination of the gray-white-matter ratio (GWR) in cranial computed tomography (CCT) obtained early after resuscitation. It is not known how GWR relates to established outcome parameters such as neuron specific enolase (NSE) or somatosensory evoked potentials (SSEP). METHODS: Cardiac arrest patients (n?=?98) treated with hypothermia were retrospectively analyzed with respect to the prognostic value of GWR, NSE and SSEP. RESULTS: A GWR?<?1.16 predicted poor outcome with 100% specificity and 38% sensitivity. In 62 patients NSE, SSEP and CCT were available. The sensitivity of poor outcome prediction by both NSE?>?97 ?g/L and bilateral absent SSEP was 43%. The sensitivity increased to 53% in a multi-parameter approach predicting poor outcome using at least two of the three parameters (GWR, NSE and SSEP). CONCLUSION: Our results suggest a strong association of a low GWR with poor outcome following cardiac arrest. Determination of the GWR increases the sensitivity in a multi-parameter approach for prediction of poor outcome after cardiac arrest.
Project description:Brain protein biomarker clearance to blood in traumatic brain injury (TBI) is not fully understood. The aim of this study was to analyze the effect that a disrupted blood-brain barrier (BBB) had on biomarker clearance. Seventeen severe TBI patients admitted to Karolinska University Hospital were prospectively included. Cerebrospinal fluid (CSF) and blood concentrations of S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) were analyzed every 6-12?h for ?1 week. Blood and CSF albumin were analyzed every 12-24?h, and BBB integrity was assessed using the CSF:blood albumin quotient (QA). We found that time-dependent changes in the CSF and blood levels of the two biomarkers were similar, but that the correlation between the biomarkers and QA was lower for NSE (??=?0.444) than for S100B (??=?0.668). Because data were longitudinal, we also conducted cross correlation analyses, which indicated a directional flow and lag-time of biomarkers from CSF to blood. For S100B, this lag-time could be ascribed to BBB integrity, whereas for NSE it could not. Upon inferential modelling, using generalized least square estimation (S100B) or linear mixed models (NSE), QA (p?=?0.045), time from trauma (p?<?0.001), time from trauma2 (p?=?0.023), and CSF biomarker levels (p?=?0.008) were independent predictors of S100B in blood. In contrast, for NSE, only time from trauma was significant (p?<?0.001). These findings are novel and important, but must be carefully interpreted because of different characteristics between the two proteins. Nonetheless, we present the first data that indicate that S100B and NSE are cleared differently from the central nervous system, and that both the disrupted BBB and additional alternative pathways, such as the recently described glymphatic system, may play a role. This is of importance both for clinicians aiming to utilize these biomarkers and for the pathophysiological understanding of brain protein clearance, but warrants further examination.
Project description:BACKGROUND:In a rabbit model of cardiopulmonary bypass (CPB) and cardioplegic arrest, we previously showed that hyperoxic myocardial reperfusion was associated with increased left ventricular (LV) systolic dysfunction and myocardial injury compared with normoxic reperfusion. The aim of this study was to evaluate in our experimental model the impact of post-CPB reperfusion conditions on other organs potentially vulnerable to ischemic injury such as the brain and kidney. METHODS:After 60?min of CPB, aortic cross-clamp, and cold cardioplegic arrest, rabbits were reperfused under hyperoxic or normoxic conditions for 120?min. Left ventricular systolic contractility (LV?+?dP/dt) and diastolic relaxation (LV -dP/dt) were continuously recorded, and end-organ injury was assessed by measuring circulating biomarkers specific for kidney (cystatin C and creatinine) and brain injury [S100B and neuron specific enolase (NSE)]. At completion of the protocol, kidney and brain tissues were harvested for measuring oxidant stress (OS), inflammation and apoptosis. RESULTS:Following aortic cross-clamp removal, rabbits exposed to normoxic reperfusion demonstrated preserved LV systolic and diastolic function compared with hyperoxic reperfusion (LV?+?dP/dt: 70?±?14% of pre-CPB vs. 36?±?21%, p?=?0.018; LV -dP/dt: 72?±?36% of pre-CPB vs. 33?±?20%, p?=?0.023). Similarly, CPB increased plasma creatinine, S100B and NSE that were significantly attenuated by normoxic reperfusion compared with hyperoxic reperfusion (creatinine: 4.0?±?0.5 vs. 7.1?±?0.8?mg/dL, p?=?0.004; S100B: 4.0?±?0.8 vs. 6.7?±?1.0?ng/mL, p?=?0.047; NSE: 57.7?±?6.8 vs. 101.3?±?16.1?pg/mL, p?=?0.040). Furthermore, both kidney and brain tissues showed increased mRNA expression and activation of pathways for OS, inflammation, and apoptosis, that were reduced under normoxic compared with hyperoxic conditions. CONCLUSIONS:Normoxic reperfusion ameliorates cardiac, renal and neural injury compared with hyperoxic reperfusion in an in vivo animal model of CPB and cardioplegic arrest. This protective effect of normoxic reperfusion may be due to a reduction in signaling pathways for OS, inflammation, and apoptosis.