Search

Background and Objectives: Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD., Methods: MEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge g method with a random-effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305)., Results: The search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, p < 0.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, p < 0.0001). Both biomarkers were elevated in more advanced clinical stages of the disease (i.e., in AD dementia compared with MCI due to AD: GFAP effect size 0.48, 95% CI 0.19-0.76, p = 0.0009; YKL-40 effect size 0.34, 95% CI 0.10-0.57, p = 0.0048). No significant differences in blood S100B levels were identified., Discussion: We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.

Abstract: Background : COVID-19 disease severity markers include mostly molecules related to not only tissue perfusion, inflammation, and thrombosis, but also biomarkers of neural injury. Clinical and basic research has demonstrated that SARS-COV-2 affects the central nervous system. The aims of the present study were to investigate the role of neural injury biomarkers and to compare them with inflammatory markers in their predictive ability of mortality. Methods : We conducted a prospective observational study in critically ill patients with COVID-19 and in a cohort of patients with moderate/severe disease. S100b, neuron-specific enolase (NSE), and inflammatory markers, including soluble urokinase plasminogen activator receptor (suPAR), were measured on intensive care unit or ward admission, respectively. Statistical comparisons between patient groups were performed for all biomarkers under investigation. Correlations between different biomarkers were tested with Spearman correlation coefficient. Receiver operating characteristic curves were plotted using mortality as the classification variable and the biomarker levels on admission as the prognostic variables. Results : A total of 70 patients with COVID-19 were included in the final analysis. Of all studied biomarkers, s100b had the best predictive ability for death in the intensive care unit, with an area under the curve of 0.73 (0.61-0.83), P = 0.0003. S100b levels correlated with NSE, interleukin (IL)-8, and IL-10 (0.27 < rs < 0.37, P < 0.05), and tended to correlate with suPAR ( rs = 0.26, P = 0.05), but not with the vasopressor dose ( P = 0.62). Conclusion : Among the investigated biomarkers, s100b demonstrated the best predictive ability for death in COVID-19 patients. The overall biomarker profile of the patients implies direct involvement of the nervous system by the novel coronavirus., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Background: Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade., Methods: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007)., Results: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 μg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 μg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 μg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort., Conclusions: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock., Methods: This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multicenter, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100β were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate., Results: Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve., Conclusion: Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β., Trial Registration: NCT, ClinicalTrials.gov NCT03756220, ATESS. Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Abstract: The aim of this study was to investigate the associations between the levels of neuron-specific enolase (NSE) and S100B protein and coma duration, and evaluate the optimal cut-off values for prediction coma duration ≥ 72 hours in patients with acute carbon monoxide poisoning (ACOP).A total of 60 patients with ACOP were divided into 3 following groups according to their status of consciousness and coma duration at admission: Awake group [Glasgow Coma Scale score (GCS score) ≥ 13 points], Coma < 72 hours group (GCS score < 13 points and coma duration < 72 h), and Coma ≥ 72 hours group (GCS score < 13 points and coma duration ≥ 72 h). The levels of serum NSE and S100B protein were measured after admission.There were significant differences in GCS score, carbon monoxide (CO) exposure time, NSE, and S100B levels between the Coma ≥ 72 h group and the Awake group, and between the Coma < 72 h group and the Awake group. Significant differences in GCS score, NSE, and S100B levels were also found between Coma ≥ 72 h group and Coma < 72 h group. Correlation analysis showed that NSE and S100B were positively correlated (rs = 0.590, P < .01); NSE and S100B were negatively correlated with GCS score (rs = -0.583, rs = -0.590, respectively, both P < .01). The areas under the curve (AUCs) of NSE, S100B, and GCS score to predict the coma duration ≥ 72 hours were 0.754, 0.791, and 0.785, respectively. Pairwise comparisons did not show differences among the 3 groups (all P > .05). The sensitivity and specificity of NSE prediction with a cut-off value of 13 μg/L were 80% and 64%, respectively, and those of S100B prediction with a cut-off value of 0.43 μg/L were 70% and 88%, respectively.The NSE and S100B protein levels were significantly correlated with the degree of impaired consciousness and had the same clinical value in predicting coma duration of ≥ 72 hours in patients with ACOP., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: To investigate whether plasma concentrations of S100β protein, neuron-specific enolase (NSE), and neuroglobin (NGB) correlate with early postoperative cognitive dysfunction (POCD) in patients undergoing total arch replacement.This prospective study analyzed 40 patients who underwent total arch replacement combined with stented elephant trunk implantation at our hospital between March 2017 and January 2019. Cognitive function was assessed using the Mini-mental State Examination (MMSE) preoperatively, on the day after extubation and on day 7 after surgery. Plasma levels of S100β, NSE, and NGB POCD were assayed preoperatively and at 1, 6, and 24 hours after cardiopulmonary bypass. POCD was defined as a decrease of at least 1 unit in the MMSE score from before surgery until day 7, and patients were stratified into those who experienced POCD or not. The 2 groups were compared in clinicodemographic characteristics and plasma levels of the 3 proteins.Plasma levels of all 3 biomarkers increased significantly during and after cardiopulmonary bypass. Levels of S100β and NSE, but not NGB, were significantly higher in the 15 patients who showed POCD than in the remainder who did not. For prediction of early POCD, S100β showed an area under the receiver operating characteristic curve (AUC) of 0.71 (95% confidence interval [CI] 0.55-0.87), sensitivity of 48%, and specificity of 87%. The corresponding values for NSE were 0.77 (95%CI 0.60-0.94), 92%, and 67%. Together, S100β and NSE showed an AUC of 0.81 (95%CI 0.66-0.96), sensitivity of 73%, and specificity of 80%. NGB did not significantly predict early POCD (AUC 0.62, 95%CI 0.43-0.80).Plasma S100β protein and NSE, but not NGB, may help predict early POCD after total arch replacement., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT)., Methods: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated., Results: We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score ( p = 0.364) or occur-to-treatment time ( p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-β ( p = 0.007) and higher vascular endothelial growth factor ( p = 0.003) levels in the RIPC group than in the control group., Conclusions: Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS., Clinicaltrialsgov Identifier: NCT03218293., Classification of Evidence: This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days., (© 2020 American Academy of Neurology.)

Benign convulsions with mild gastroenteritis (CwG) and febrile seizures (FS) associated with mild gastroenteritis are 2 different diseases in the spectrum of seizures associated with mild gastroenteritis. However, specific and useful indicators for the identification of the 2 diseases are lacking. A retrospective analysis was performed to compare the serum neuronal-specific enolase (NSE) and S100B protein levels between patients with these 2 diseases to evaluate the value of NSE and S100B for differential diagnosis between these 2 diseases.The clinical data and NSE and S100B protein levels of 81 children with seizure-associated mild gastroenteritis were collected. According to the axillary temperature at the time of convulsions, all patients were classified into an afebrile seizure (AFS) group, hereafter called the CwG group (n = 46), and a febrile seizure group (FS group, n = 35).The serum NSE level was higher in the CwG group than in the FS group (14.046 (11.095, 19.266) pg/ml and 9.034 (7.158, 12.165) pg/ml, respectively, P < .001); however, the serum S100B protein levels in the CwG and the FS group were not significantly different (P > .05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for NSE was 0.806, P = .000, which was statistically significant. The Youden index was largest (0.605) for a serum NSE cut-off value of 10.460 pg/ml, which yielded a sensitivity and specificity of 89% and 71%, respectively, for prediction of a CwG diagnosis.NSE may contribute to the differential diagnosis of CwG and FS associated with mild gastroenteritis.

Background: Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA., Methods: Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery., Results: Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001)., Conclusion: S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported.

To study the correlation between single nucleotide polymorphism (SNP) of the 3' untranslated region (UTR) rs9722 locus in S100B and the risk of chronic heart failure (CHF), plasma levels of S100B protein as well as has-miR-340-3p in a Chinese Han population.A total of 215 patients with CHF (124 ischemic cardiomyopathy (ICM) and 91 dilated cardiomyopathy (DCM)) and 215 healthy controls were recruited to analyze the S100B rs9722 genotype by Sanger sequencing. The levels of hsa-miR-340-3p in the plasma were detected by RT-PCR, and S100B levels were detected by ELISA.The risk of CHF in S100B rs9722 locus T allele carriers was 4.24 times higher than that in those with the C allele (95% CI: 2.84-6.33, P < .001). The association of S100B rs9722 locus SNP with ICM and DCM risk was not affected by factors such as age, gender, and body mass index (BMI). The levels of plasma S100B and hsa-miR-340-3p in patients with ICM and DCM were significantly higher than those in the control group (P < .001). There was no significant difference in plasma S100B levels between patients with ICM and DCM (P > .05). Among ICM, DCM, and control subjects, TT genotype carriers had the highest levels of plasma S100B and hsa-miR-340-3p, followed by the CT genotype and TT genotype, and the difference was statistically significant (P < .05). Plasma hsa-miR-340-3p levels were positively correlated with S100B levels in the control subjects and patients with ICM and DCM.The S100B rs9722 locus SNP is associated with CHF risk in a Chinese Han population.

Background: Although surgical field visualization is important in functional endoscopic sinus surgery (FESS), the complications associated with controlled hypotension for surgery should be considered. Intraoperative hypotension is associated with postoperative stroke, leading to subsequent hypoxia with potential neurologic injury. We investigated the effect of propofol and desflurane anesthesia on S-100β and glial fibrillary acidic protein (GFAP) levels which are early biomarkers for cerebral ischemic change during controlled hypotension for FESS., Methods: For controlled hypotension during FESS, anesthesia was maintained with propofol/remifentanil in propofol group (n = 30) and with desflurane/remifentanil in desflurane group (n = 30). For S-100β and GFAP assay, blood samples were taken at base, 20 and 60 minutes after achieving the target range of mean arterial pressure, and at 60 minutes after surgery., Results: The base levels of S-100β were 98.04 ± 78.57 and 112.61 ± 66.38 pg/mL in the propofol and desflurane groups, respectively. The base levels of GFAP were 0.997 ± 0.486 and 0.898 ± 0.472 ng/mL in the propofol and desflurane groups, respectively. The S-100β and GFAP levels were significantly increased in the study period compared to the base levels in both groups (P ≤ .001). There was no significant difference at each time point between the 2 groups., Conclusion: On comparing the effects of propofol and desflurane anesthesia for controlled hypotension on the levels of S-100β and GFAP, we noted that there was no significant difference in S-100β and GFAP levels between the 2 study groups., Clinical Trial Registration: Available at: http://cris.nih.go.kr, KCT0002698.

The identification of hypothermia as the cause of death remains challenging in forensic pathology because of unspecific radiological, morphological, and biochemical results. Hyperemia, edema, and petechial hemorrhages within the cerebral parenchyma were described in cases of death by hypothermia. On the other hand, the effect of low temperatures in the brain has been speculated to cause local injuries on a cellular level with potential occurrences of necrosis and inflammation. In the study herein described, endocan, alkaline phosphatase, neuron-specific enolase, S100 protein subunit B, glial fibrillary acidic protein, and C-reactive protein were measured in postmortem serum from femoral blood and cerebrospinal fluid in a series of hypothermia fatalities and control cases. The combination of data collected failed to identify a specific biochemical profile for death by hypothermia in postmortem serum and/or the cerebrospinal fluid, thus suggesting that an alternative panel of brain damage biomarkers indicative of diffuse hypoxic brain injury needs to be defined in hypothermia fatalities.

Background: Pediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic encephalopathy (HE) is a complication of PALF with limited diagnostic tools to predict outcomes. Serum neurological markers (neuron-specific enolase, S100β, and myelin basic protein) can be elevated in traumatic or ischemic brain injury. We hypothesized that these neuromarkers would be associated with the development of HE in PALF., Methods: PALF study participants enrolled between May 2012 and December 2014 by 12 participating centers were the subjects of this analysis. Daily HE assessments were determined by study investigators. Neurological and inflammatory markers were measured using enzyme-linked immunosorbent assay and MILLIPLEX techniques, respectively. To model encephalopathy, these markers were log2 transformed and individually examined for association with HE using a generalized linear mixed model with a logit link and random intercept., Results: Eighty-two children had neurological and inflammatory marker levels and HE assessments recorded, with the majority having assessments for 3 days during their illness. An indeterminate diagnosis (29%) was most common and the median age was 2.9 years. Significant associations were observed for HE with S100β (odds ratio 1.16, 95% confidence interval [1.03-1.29], P = 0.04) and IL-6 (odds ratio 1.24 [1.11-1.38], P = 0.006)., Conclusions: Serum S100β and IL-6 are associated with HE in children with PALF. Measuring these markers may assist in assessing neurological injury in PALF, impacting clinical decisions.

Background and Purpose- S100B protein serum elevation has been associated with poor prognosis in neurologically ill patients. The purpose of this study is to determine whether elevation of S100B is associated with increased in-hospital mortality after brain arteriovenous malformation rupture. Methods- This is a retrospective study of patients admitted for brain arteriovenous malformation rupture. The study population was divided into derivation and validation cohorts. Univariate followed by multivariate logistic regression was used to determine whether elevation of S100B serum levels above 0.5 µg/L during the first 48 hours after admission (S100Bmax48) was associated with in-hospital mortality. Results- Two hundred and three ruptures met inclusion criteria. Twenty-three led to in-hospital mortality (11%). Mean S100Bmax48 was 0.49±0.62 µg/L. In the derivation cohort (n=101 ruptures), multivariate analysis found Glasgow coma scale score ≤8 (odds ratio, 21; 95% CI, 2-216; 0.001) and an S100Bmax48>0.5 µg/L (odds ratio, 19; 95% CI, 2-188; P=0.001) to be associated with in-hospital mortality. When applied to the validation cohort (n=102 ruptures), the same model found only S100Bmax48>0.5 µg/L (odds ratio, 8; 95% CI, 1.5-44; P=0.01) to be associated with in-hospital mortality. Conclusions- Elevated S100B protein serum level is strongly associated with in-hospital mortality after brain arteriovenous malformation rupture.

This study aimed to determine whether the combination of procalcitonin (PCT) and S100B improves prognostic performance compared to either alone in cardiac arrest (CA) patients treated with targeted temperature management (TTM).We performed a prospective cohort study of CA patients treated with TTM. PCT and S100B levels were obtained at 0, 24, 48, and 72 hours after return of spontaneous circulation. The prognostic performance was analyzed using each marker and the combination of the 2 markers for predicting poor neurological outcome at 3 months and mortality at 14 days and 3 months.A total of 97 patients were enrolled, of which 67 (69.1%) had poor neurological outcome. S100B showed a better prognostic performance (area under the curve [AUC], 0.934; sensitivity, 77.6%; and specificity, 100%) than PCT (AUC, 0.861; sensitivity, 70.2%; and specificity, 83.3%) with the highest prognostic value at 24 hours. The combination of 24-hour PCT and S100B values (S100B ≥0.2 μg/L or PCT ≥6.6 ng/mL) improved sensitivity (85.07%) compared with S100B alone. In multivariate analysis, PCT was associated with mortality at 14 days (odds ratio [OR]: 1.064, 95% confidence interval [CI]: 1.014-1.118), whereas S100B was associated with neurological outcomes at 3 months (OR: 9.849, 95% CI: 2.089-46.431).The combination of PCT and S100B improved prognostic performance compared to the use of either biomarker alone in CA patient treated with TTM. Further studies that will identify the optimal cutoff values for these biomarkers must be conducted.

Objective: To explore the effect of ginkgo biloba extract (EGb) as an adjunctive treatment of elderly patients with depression and the effect on the expression of serum S100B., Methods: 136 elderly patients with depression were divided into EGb +  citalopram (Cit) group and Cit group equally. Efficacy was evaluated by Hamilton Depression Rating Scale (HAMD). Wisconsin Card Classification Test (WCST) was used to evaluate cognitive function. Serum S100B expression was measured with ELISA. The relationship of S100B with HAMD, Hamilton Anxiety Scale (HAMA) score, and WCST results was evaluated subsequently., Results: The time of onset of efficacy was significantly shorter in EGb + Cit group. There were significant differences in HAMD and HAMA scores after treatment than before treatment between groups (all P < .05). After treatment, total number of WCST test, the number of continuous errors and non-persistent errors in both groups were less than those before treatment. The correct number and classifications number were increased than before treatment. In EGb + Cit group, correct numbers and classifications were increased, and the number of persistent errors was decreased. After treatment, S100B level was decreased, and S100B levels change in EGb + Cit group was greater than in Cit group. Serum S100B level was positively correlated with HAMD and HAMA scores before treatment and positively correlated with persistent errors number in WCST., Conclusion: EGb, as an adjunctive treatment, can effectively improve depressive symptoms and reduce expression of serum S100B, which is a marker of brain injury, suggesting that EGb restores neurologic function during the treatment of depression in elderly patients and S100B participates in the therapeutic mechanism. EGb combined with depressive drugs plays synergistic role, and the time of onset of efficacy is faster than single antidepressants.

Objective: To compare neurofilament light (NfL) and tau as blood-based biomarkers for acute sports-related concussion (SRC) and determine whether their concentrations at different time points after the injury are associated with prolonged time to return to play (RTP)., Methods: A total of 288 professional hockey players were followed longitudinally from September 1, 2012, to April 30, 2015. Data collection and biomarker analyses were conducted between 2015 and 2017. Associations were tested between blood concentrations of NfL and tau, and RTP time. Serum concentrations of S100B and neuron-specific enolase (NSE) were also measured for comparison., Results: Of 288 players, 105 sustained an SRC. Of these, 87 underwent blood sampling 1, 12, 36, and 144 hours after SRC and at the RTP time point. Serum NfL concentrations 1, 12, 36, and 144 hours after SRC were related to prolonged RTP time, and could separate players with RTP >10 days from those with RTP ≤10 days (area under the receiver operating characteristic curve [AUROC] 0.82). Also, serum NfL 144 hours after SRC discriminated players who resigned from the game due to persistent postconcussion symptoms (PCS) from those who returned to play (AUROC 0.89). Plasma tau 1 hour after SRC was related to RTP but less strongly than NfL, while S100B and NSE showed no such associations., Conclusion: Serum NfL outperformed tau, S100B, and NSE as a biomarker for SRC. From a clinical standpoint, serum NfL may be useful to identify individuals at risk of prolonged PCS, and may aid in biomarker-informed decisions with regard to when RTP should be considered., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The initial diagnosis of neonatal hypoxic-ischemic encephalopathy is based on nervous system clinical manifestations. The use of biomarkers to monitor brain injury and evaluate neuroprotective effects allows early intervention and treatment. This study was designed to determine the short-term prognostic significance of urinary S100B calcium-binding protein (S100B) in asphyxiated newborns treated with hypothermia.An observational prospective study was conducted over a period of 5 years in 31 newborns with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. The patients were divided into 2 groups: Group A (13 newborns with a normal neurological examination before discharge) and Group B (18 newborns who died during admission or had an abnormal neurologic examination before discharge). Urinary S100B was the main variable, serum S100B and neuron-specific enolase (NSE) were considered as secondary variables, and all of them were assessed on the first 3 days of life. The newborns were subsequently divided into groups with normal and abnormal electrophysiological and imaging findings.Mean urinary S100B levels were significantly higher in group B than group A on day 1 (10.58 ± 14.82 vs 4.65 ± 9.16 μg/L, P = .031) and day 2 (5.16 ± 7.63 vs 0.88 ± 2.53, P = .002). The optimal cutoff for urinary S100B on day 1 was >1.11 μg/L of (sensitivity, 100%; specificity 60%) for the prediction of neonatal death and < 0.66 μg/L (sensitivity 83% and specificity 70%) for the prediction of a normal neurological examination before discharge. It was not possible to calculate cutoffs with a similar accuracy for serum S100B or NSE. Urinary S100B on day 1 was higher in patients with abnormal magnetic resonance imaging findings (7.89 ± 8.09 vs 4.49 ± 9.14, P = .039) and abnormal positron emission tomography findings (8.60 ± 9.29 vs 4.30 ± 8.28, P = .038). There were no significant differences in S100B levels between patients with normal and abnormal electroencephalography results.Urinary S100B measured in the first days of life can predict neonatal death and short-term prognosis in asphyxiated newborns treated with hypothermia. The method is convenient, noninvasive, and has a higher sensitivity and specificity than measurement of serum S100B or NSE.

Background and Purpose: Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase., Methods: The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves., Results: From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71; P <0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19-3.45; P =0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%., Conclusions: The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke., (© 2017 American Heart Association, Inc.)

The objective of this study was to summarize the incidence of postoperative cognitive dysfunction (POCD) after 7days following liver transplantation (LT), and to evaluate the effectiveness of bispectral index (BIS) guided anesthetic intervention in reducing POCD. Additional serum concentrations of S100β and neuron-specific enolase (NSE) were detected during surgery to determine whether they were reliable predictors of POCD.Patients who underwent LT at Beijing YouAn Hospital Affiliated to Capital University of Medical Science from January 2014 to December 2015 were enrolled. BIS monitor was needed during surgery. Patients who underwent LT without BIS monitoring during August 2012 to December 2014 served as historical controls. A battery of 5 neuropsychological tests were performed and scored preoperatively and 7days after surgery. POCD was diagnosed by the method of one standard deviation (SD). The blood samples of BIS group were collected at 5 time points: just before induction of general anesthesia (T0), 60 minutes after skin incision (T1), 30 minutes after the start of the anhepatic phase (T2), 15 minutes after reperfusion of the new liver (T3), and at 24 hours after surgery (T4).A total of 33 patients were included in BIS group, and 27 in the control group. Mean arterial pressure was different between 2 groups at 30 minutes after the start of the anhepatic phase (P = .032). The dose of propofol using at anhepatic phase 30 min and new liver 15 min was lower in the BIS group than control group (0.042 ± 0.021 vs. 0.069 ± 0.030, P < .001; 0.053 ± 0.022 vs. 0.072 ± 0.020, P = .001). Five patients were diagnosed as having POCD after 7 days in the BIS group and the incidence of POCD was 15.15%. In the control group, 9 patients had POCD and the incidence of POCD was 33.33%. The incidence of POCD between 2 groups had no statistical difference (P = .089). S100β increased at stage of anhepatic 30 minutes (T2) and new liver 15 minutes (T3) compared with the stage of before anesthesia (T0) (1.49 ± 0.66 vs. 0.72 ± 0.53, P < .001; 1.92 ± 0.78 vs. 0.72 ± 0.53, P < .001). NSE increased at stage of anhepatic 30 minutes (T2) and new liver 15 minutes (T3) compared with the stage of before anesthesia (T0) (5.80 ± 3.03 vs. 3.58 ± 3.24, P = .001; 10.04 ± 5.65 vs. 3.58 ± 3.24, P < .001). At 24 hours after surgery, S100β had no difference compared to one before anesthesia (1.0 ± 0.62 vs. 0.72 ± 0.53, P = .075), but NSE still remained high (5.19 ± 3.64 vs. 3.58 ± 3.24, P = .043). There were no significant differences in the serum concentrations of S100β between patients with and without POCD at 5 time points of operation (P > .05). But at 24 hours after surgery, NSE concentrations were still high of patients with POCD (8.14 ± 3.25 vs. 4.81 ± 3.50, P = .035).BIS-guided anesthesia can reduce consumption of propofol during anhepatic and new liver phase. Patients in BIS group seem to have a mild lower incidence of POCD compared to controls, but no statistical significant. The influence of BIS-guided anesthesia on POCD needs to be further confirmed by large-scale clinical study. S100β protein and NSE are well correlative with neural injury, but NSE is more suitable for assessment of incidence of postoperative cognitive deficits after surgery.

Electro-acupuncture is a burgeoning treatment using the needle inserting into the body acupoints and the low-frequency pulse current being electrified by an electric acupuncture machine. This study was designed to evaluate the effects of preconditioning of electro-acupuncture on postoperative cognitive dysfunction in elderly.Ninety patients scheduled spine surgery were randomly assigned into 2 groups using a random number table: control group (group C) and electro-acupuncture group (group EA). In group EA, electro-acupuncture was applied on Baihui, Dazhui, and Zusanli acupoints 30 minutes before anesthesia. At 0 minute before treatment of electro-acupuncture, 1 hour after skin incision and surgery completed (T1-3), blood samples were taken for detection of interleukin (IL)-6, IL-10, and S100β by enzyme-linked immunosorbent assay. The total dose of remifentanil and propofol during surgery were recorded. Mini-Mental State Examination was applied to evaluate the cognitive function of patients at 1 day before surgery and 7th and 30th day after surgery.The results showed that compared with group C, score of MMSE increased after surgery, the serum concentration of IL-6, IL-10, and S100β decreased at 1 hour after skin incision, and surgery completed in group EA. Moreover, the total dose of remifentanil and propofol reduced during surgery in group EA.The present study suggests that preconditioning of electro-acupuncture could improve the postoperative cognitive function, and the reduction of inflammatory reaction and brain injury may be involved in the mechanism.

Nimodipine is a clinical commonly used calcium antagonistscan lowering the apoptosis rate of hippocampal neuron to reduce the incidence of postoperative cognitive dysfunction (POCD). This study was designed to evaluate the effects of nimodipine on postoperative delirium in elderly under general anesthesia.Sixty patients shceduced spine surgery under general anesthesia were randomly assigned into 2 groups using a random number table: control group (Group C) and nimodipine group (Group N). In Group N, nimodipine 7.5 μg/(kg × h) was injected continually 30 minutes before anesthesia induction, while the equal volume of normal saline was given in Group C. At 0 minute before injection, 0 minute after tracheal intubation, 1 hour after skin incision and surgery completed (T1-4), blood samples were taken from the radial artery and jugular bulb for blood gas analysis. Cerebral oxygen metabolism-related indicators were calculated at the same time. Concentration of S100β and glial fibrillary acidic protein (GFAP) were tested by ELISA. The incidence of postoperative delirium within 7 days after surgery was recorded.Cerebral oxygen metabolism-related indicators fluctuationed in the normal range in 2 groups at different time points and the difference were not statistically significant. Compared with Group C, S100β and GFAP decreased and incidence of postoperative delirium reduced at T3-4 in Group N, the difference was statistically significant (P<.05).The present study suggests that nimodipine can reduce the development of postoperative delirium in elderly patients under general anesthesia, the reduction of brain injury and improvement of cerebral oxygen metabolism may be involved in the mechanism.

Background: Cognitive function impairment is one of the most common complications in elderly patients after surgery, and an ideal nonpharmacological therapy has not yet been identified. Thus, we hypothesized that remote ischemic preconditioning could improve cognitive functions in elderly patients after surgery and investigated the mechanism underlying this effect., Methods: Ninety patients classified as American Society of Anaesthesiologists (ASA) physical status of 2 or 3 and aged 65 to 75 years who were scheduled for elective colon surgery under general anesthesia were randomly allocated to either a remote ischemic preconditioning group (Group R, n = 45) or a control group (Group C, n = 45). Remote ischemic preconditioning was performed by applying a static pressure of 200 mm Hg with a blood pressure cuff wrapped around the right upper limb for 3 ischemia cycles of 5 minutes each., Results: The Montreal Cognitive Assessment (MoCA) scores between the 2 groups were not significantly different on the day before surgery or the seventh day after surgery, but the scores on the first day after surgery (26.87 ± 0.84 vs 25.96 ± 0.85, P < .001) and third day after surgery (27.49 ± 0.66 vs 27.02 ± 0.92, P = .009) were significantly higher for Group R than those for Group C. Moreover, remote ischemic preconditioning markedly decreased the serum concentrations of the interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and S100B proteins compared with the control group (P < .001)., Conclusion: Remote ischemic preconditioning improves postoperative cognitive function in elderly patients following colon surgery. The cognitive protective effects of remote ischemic preconditioning are partially related to the inhibition of inflammation.

Objectives: During critical illness, impaired endothelial vascular reactivity predicts prolonged acute brain dysfunction, but relationships between endothelial activation, blood-brain barrier/neurological injury, and acute brain dysfunction, including delirium, remain unexamined. We tested the hypothesis that elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury are associated with delirium duration during critical illness., Design: Prospective cohort study., Setting: Medical and surgical ICUs in an academic medical center., Patients: Adults in acute respiratory failure and/or shock., Interventions: None., Measurements and Main Results: We enrolled subjects within 72 hours of organ failure diagnosis in the ICU. We measured plasma concentrations of plasminogen activator inhibitor-1, E-selectin, and angiopoietin-2 as markers of endothelial activation and S100B as a marker of blood-brain barrier/neurological injury in blood collected at enrollment. We assessed patients for delirium and coma twice daily after enrollment using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Among 134 patients with a median (interquartile) age of 57 years (46-66 yr) and Acute Physiology and Chronic Health Evaluation II of 26 (19-31), delirium occurred in 94 patients (70%) with a median duration of 2 days (0-4 d). Higher plasminogen activator inhibitor-1 (p = 0.002), E-selectin (p = 0.02), and S100B (p < 0.001) concentrations were associated with fewer delirium/coma-free days after adjusting for age, Charlson comorbidity index, modified Sequential Organ Failure Assessment score, and severe sepsis. Similarly, higher plasminogen activator inhibitor-1 (p = 0.007) and S100B (p = 0.01) concentrations were associated with longer delirium duration in survivors. Adjusting for S100B did not alter plasminogen activator inhibitor-1 and E-selectin associations with delirium, suggesting that these associations were not mediated by blood-brain barrier/neurological injury., Conclusions: Elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury during critical illness are associated with prolonged delirium after biomarker measurement. Future research is needed to determine whether these processes have pathophysiologic roles in delirium and whether therapies targeted at the endothelium or blood-brain barrier can prevent and/or treat delirium during critical illness.

The authors evaluated neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and heat shock protein 70 (HSP 70) levels and their relationships with in-hospital mortality, Glasgow Coma Scale (GCS) scores, and National Institute of Health Stroke Scale (NIHSS) scores. In total, 35 patients older than 18 years were presented to our emergency department and were diagnosed with non-traumatic intracranial hemorrhage (ICH) and 32 healthy controls were included. Blood samples were drawn on days 0 and 5. S100 calcium-binding protein B and HSP levels were significantly higher in patients than in controls on days 0 and 5. Neuron-specific enolase levels were higher in patients than in controls on day 0, but there was no significant difference on day 5. S100 calcium-binding protein B was negatively correlated with GCS, whereas it was positively correlated with NIHSS and bleeding volume. There was also a negative correlation between NSE and GCS, but it was not statistically significant. In addition, no significant correlation was found in terms of bleeding volume or NIHSS. Heat shock protein 70 was negatively correlated with GCS and positively correlated with bleeding volume and NIHSS, but these results were not statistically significant. S100 calcium-binding protein B and HSP 70 levels were significantly higher in those who died compared with survivors. The areas under the curve of S100 B, NSE, and HSP 70 for mortality were 0.635, 0.477, and 0.770, respectively. Neuron-specific enolase, S100B, and HSP 70 levels are simple, inexpensive, and objective measures in cases of ICH. These tests can be used to support an assessment for screening ICH patients with clinical scoring systems, such as GCS and NIHSS.

Minor head trauma is a common reason for consultation in pediatric emergency departments. In 2009, the Pediatric Emergency Care Applied Research Network (PECARN) published a clinical decision rule for its management. It aimed to help clinicians identify children with a very low risk of developing intracranial lesions, so that unnecessary cranial computed tomography (CCT) scan radiation could be avoided, as such exposure is associated with a rising risk of cancer in this young population. In the meantime, the serum S100β neuroprotein showed encouraging results, with a 30% potential decrease in CCTs for the management of minor head traumas in adults and children. The aim of this study was to determine if the serum S100β neuroprotein, associated with the PECARN clinical decision rule, could safely reduce the use of CCTs. We included children who were examined at the pediatric emergency department for minor head trauma, who underwent a CCT, whose blood samples were analyzed to determine the level of the serum S100β protein. They were managed according to the PECARN clinical decision rule. We afterward assessed the potential decrease in the number of CCTs, according to a modified PECARN clinicobiological decision rule, had we taken into account the result of the blood tests. One hundred nine children were included, and nine of them had clinically important traumatic brain injury. Four of them had a negative S100β value but were classified as high risk of developing intracranial lesion according to the PECARN clinical decision rule. Had we taken into account the modified PECARN clinicobiological decision rule, none of them would have been missed. However, there were 32 true negatives of the rule, allowing a potential decrease in CCTs rated at 29% (95% confidence interval, 21-38). Integrating the serum S100β neuroprotein assessment in the PECARN clinical decision rule could avoid deleterious exposure to CCT radiation, with the condition of using a clinicobiological rule to avoid missing clinically important traumatic brain injuries. Those results have yet to be confirmed relying on a large multicentric study.

Objectives: To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy., Design: Prospective longitudinal cohort study., Setting: A level IV neonatal ICU in a freestanding children's hospital., Patients: Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period., Interventions: Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia., Measurements and Main Results: Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (< 70), or died. Elevated serum S100B and neuron-specific enolase levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and socioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were 2.5 (95% CI, 1.3-4.8) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase, and for motor outcome, 2.6 (95% CI, 1.2-5.6) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase., Conclusions: Serum S100B and neuron-specific enolase levels in babies with neonatal encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia.

Background: Sudden cardiac arrest is a leading cause of death worldwide. Three-fourths of cardiac arrest patients die before hospital discharge or experience significant neurological damage. Hydrogen-rich saline, a portable, easily administered, and safe means of delivering hydrogen gas, can exert organ-protective effects through regulating oxidative stress, inflammation, and apoptosis. We designed this study to investigate whether hydrogen-rich saline treatment could improve survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation, and the mechanism responsible for this effect., Methods: Sprague-Dawley rats were subjected to 8 minutes of cardiac arrest by asphyxia. Different doses of hydrogen-rich saline or normal saline were administered IV at 1 minute before cardiopulmonary resuscitation, followed by injections at 6 and 12 hours after restoration of spontaneous circulation, respectively. We assessed survival, neurological outcome, oxidative stress, inflammation biomarkers, and apoptosis., Results: Hydrogen-rich saline treatment dose dependently improved survival and neurological function after cardiac arrest/resuscitation. Moreover, hydrogen-rich saline treatment dose dependently ameliorated brain injury after cardiac arrest/resuscitation, which was characterized by the increase of survival neurons in hippocampus CA1, reduction of brain edema in cortex and hippocampus, preservation of blood-brain barrier integrity, as well as the decrease of serum S100β and neuron-specific enolase. Furthermore, we found that the beneficial effects of hydrogen-rich saline treatment were associated with decreased levels of oxidative products (8-iso-prostaglandin F2α and malondialdehyde) and inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and high-mobility group box protein 1), as well as the increased activity of antioxidant enzymes (superoxide dismutase and catalase) in serum and brain tissues. In addition, hydrogen-rich saline treatment reduced caspase-3 activity in cortex and hippocampus after cardiac arrest/resuscitation., Conclusions: Hydrogen-rich saline treatment improved survival and neurological outcome after cardiac arrest/resuscitation in rats, which was partially mediated by reducing oxidative stress, inflammation, and apoptosis.

Objectives: The relationship of cerebral saturation measured by near-infrared spectroscopy with serum biomarker of brain injury S100B was investigated in infants undergoing cardiac surgery with cardiopulmonary bypass., Design: Prospective cohort study., Setting: Single-center children's hospital., Patients: Forty infants between 1 and 12 months old weighing greater than or equal to 4 kg with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass were enrolled., Interventions: None., Measurements and Main Results: Serum S100B was measured at eight time points over 72 hours using enzyme-linked immunosorbent assay. Physiologic data including arterial, cerebral, and somatic regional oxygen saturations measured by near-infrared spectroscopy were synchronously recorded at 1-minute intervals from anesthesia induction through 72 postoperative hours. The arterial-cerebral oxygen saturation difference was calculated as the difference between arterial saturation and cerebral regional saturation. Thirty-eight patients, 5.4 ± 2.5 months old, were included in the analysis; two were excluded due to the use of postoperative extracorporeal membrane oxygenation. Seventeen patients (44.7%) had preoperative cyanosis. S100B increased during cardiopulmonary bypass in all patients, from a median preoperative baseline of mean ± SE: 0.055 ± 0.038 to a peak of 0.610 ± 0.038 ng/mL, p less than 0.0001. Patients without preoperative cyanosis had a higher S100B peak at the end of cardiopulmonary bypass. Although the absolute cerebral regional saturation on cardiopulmonary bypass was not associated with S100B elevation, patients who had arterial-cerebral oxygen saturation difference greater than 50 at any time during cardiopulmonary bypass had a higher S100B peak (mean ± SE: 1.053 ± 0.080 vs 0.504 ± 0.039 ng/mL; p < 0.0001)., Conclusions: A wide cerebral arteriovenous difference measured by near-infrared spectroscopy during cardiopulmonary bypass is associated with increased serum S100B in the perioperative period and may be a modifiable risk factor for neurological injury.

Objectives: Morbidity and mortality in children with cardiac arrest largely result from neurologic injury. Serum biomarkers of brain injury can potentially measure injury to neurons (neuron-specific enolase), astrocytes (S100b), and axons (myelin basic protein). We hypothesized that serum biomarkers can be used to classify outcome from pediatric cardiac arrest., Design: Prospective observational study., Setting: Single tertiary pediatric hospital., Patients: Forty-three children with cardiac arrest., Interventions: None., Measurements and Main Results: We measured serum neuron-specific enolase, S100b, and myelin basic protein on days 1-4 and 7 after cardiac arrest. We recorded demographics, details of the cardiac arrest and resuscitation, and Pediatric Cerebral Performance Category at hospital discharge and 6 months. We analyzed the association of biomarker levels at 24, 48, and 72 hours with favorable (Pediatric Cerebral Performance Category 1-3) or unfavorable (Pediatric Cerebral Performance Category 4-6) outcome and mortality. Forty-three children (49% female; mean age of 5.9 ± 6.3) were enrolled and 17 (40%) died. Serum S100b concentrations peaked earliest, followed by neuron-specific enolase and finally myelin basic protein. Serum neuron-specific enolase and S100b concentrations were increased in the unfavorable versus favorable outcome group and in subjects who died at all time points (all p < 0.05). Serum myelin basic protein at 24 and 72 hours correctly classified survival but not good versus poor outcome. Using best specificity, serum S100b and neuron-specific enolase had optimal positive and negative predictive values at 24 hours to classify both favorable versus unfavorable outcome and survival, whereas serum myelin basic protein's best accuracy occurred at 48 hours. Receiver operator curves for serum S100b and neuron-specific enolase to classify favorable versus unfavorable outcome at 6 months were superior to clinical variables., Conclusions: Preliminary data show that serum S100b, neuron-specific enolase, and myelin basic protein may aid in outcome classification of children surviving cardiac arrest.

S100B protein, an acknowledged biomarker of brain injury, has been reported to be increased in hemorrhagic shock. Also, acute hemorrhage is associated with inflammatory response. The aim of this study was to investigate the concentrations of serum S100B and the potential relationships with interleukin 6 (IL-6), severity of tissue hypoperfusion, and prognosis in patients admitted for surgical control of severe hemorrhage. Patients undergoing elective abdominal aortic aneurysm surgery participated as control subjects. Serum samples were drawn before, at the end of surgery, and after 6 and 24 h. Sixty-four patients with severe hemorrhage (23 trauma and 41 nontrauma) and 17 control subjects were included. Increased preoperative concentrations of S100B protein (1.70 ± 2.13 and 0.81 ± 1.23 μg/L) and IL-6 (241 ± 291 and 226 ± 238 pg/mL) were found in patients with traumatic and nontraumatic reason, respectively, and remained elevated throughout 24 h. Compared with nontrauma, trauma patients exhibited higher preoperative S100B levels (P < 0.05). Overall mortality was 47%. In control subjects, preoperative S100B and IL-6 levels were within normal limits and increased at the end of surgery (P < 0.001 and P < 0.01, respectively). Preoperative S100B correlated with IL-6 (r = 0.78, P < 0.01), arterial lactate (r = 0.50, P < 0.01), pH (r = -0.45, P < 0.01), and bicarbonate (r = -0.40, P < 0.01). Multiple analysis revealed that preoperative S100B in trauma and lactate in nontrauma patients were independently associated with outcome. In predicting death, preoperative S100B yielded receiver operator characteristics curve areas of 0.75 for all patients and 0.86 for those with trauma. These results indicate that severe hemorrhage in patients without brain injury is associated with increased serum levels of S100B, which correlates with IL-6 and tissue hypoperfusion. Moreover, the predictive ability of S100B for mortality, suggests that it could be a marker of potential clinical value in identifying, among patients with severe hemorrhage, those at greater risk for adverse outcome.

Vemurafenib is a highly efficient BRAF inhibitor for metastatic melanoma patients carrying the V600 mutation: progression-free survival is prolonged to ∼ 6 months and 50-80% of the patients show objective tumor responses. S100B and lactate dehydrogenase (LDH) are established tumor markers in routine melanoma follow-up. This study evaluated their potential as response and progression markers during vemurafenib treatment. A cohort of 44 patients with stage IV melanoma disease who were treated with vemurafenib was retrospectively analyzed. Staging was performed every 6-8 weeks comprising computed tomography scans and measurement of LDH and S100B levels. Response Evaluation Criteria In Solid Tumors (RECIST) criteria were used for standardized radiological response evaluations. The correlation between response or progression and LDH and S100B levels was analyzed using accuracy tests, Spearman's rank correlation ρ, and polynominal regression analyses. There was a good correlation between S100B and LDH decline and a RECIST-confirmed response, especially when S100B and/or LDH were elevated at baseline (accuracy, 81.2% for S100B and 85.7% for LDH). However, the accuracy in case of RECIST-confirmed progression and S100B/LDH levels was low - 30.3% for S100B and 32.4% for LDH. Neither Spearman's rank correlation ρ nor polynomial regression analyses showed a correlation between the clinical course and S100B/LDH levels. Measurement of S100B and LDH levels during treatment with vemurafenib indicates an initial response; however, this does not seem to be sufficient in detecting tumor progression and is thus not an alternative to monitoring with imaging examinations.