Neuron-specific Enolase Concentrations Research Articles

Optimization of Hypoxic Brain Injuries Diagnostics in Full-Term Newborns

The problem of early diagnosis of the central nervous system damage in newborn before the onset of clinical symptoms remains relevant at the present time.The aim of the study was to optimize the hypoxic brain damage diagnosis in full-term newborns by analyzing the concentration of cytokines in the umbilical cord blood.Materials and methods. During the first stage of the study, a prospective analysis of concentrations of interleukins (IL-1β, IL-4, IL-6, IL-8, IL-10), TNF-α and neuron-specific enolase (NSE) in the umbilical cord blood serum of full-term newborns was performed. The second stage of the study included the retrospective analysis of clinical data and instrumental research methods. The main method for diagnosing in the development of hypoxic brain damage in newborns was neurosonography.Results. The development of hypoxic brain damage is evidenced by the concentration of IL-1β over 30.3 pg/ml, IL-4 – over 1.7 pg/ml, IL-6 – over 79.4 pg/ml, IL-8 – over 107.7 pg/ml, NSE – more than 10.3 ng/ml and TNF-α – more than 1.6 pg/ml in umbilical cord blood.Conclusion. The results of the study confirmed that the comprehensive assessment of the cytokines concentration in the umbilical cord blood improves the hypoxic brain damage diagnosis in newborns. Analysis of the level of these markers immediately after the birth will optimize the management tactics of newborns who have undergone hypoxic exposure in antenatal and intranatal period.

A Sandwich-Type Immunosensor Based on Pd NPs@DSHSs-Cu2O and Au NPs Functionalized Graphene Oxide Doped Poly(3,4-ethylenedioxythiophene) Nanorod for Quantitative Detection NSE

Changes in the concentration of neuron-specific enolase (NSE) can be used as an indicator for many diseases. Electrochemical immunosensor is a reliable tool for early diagnosis, but achieving ultrasensitive analysis is a pressing problem. In this work, graphene oxide doped poly (3,4-ethylenedioxythiophene) (PEDOT/GO) spindle-like nanorods prepared by liquid/liquid interface polymerization method have good stability and high conductivity. The sulfur atoms on the thiophene ring combine with gold nanoparticles (Au NPs) to further improve the efficiency of interface electron transfer. Besides, the exposed carboxyl groups and Au NPs on the surface of PEDOT/GO can effectively couple with the capture antibody (Ab1). Double-shelled Cu2O hollow spheres (Pd NPs@DSHSs-Cu2O) modified with palladium nanoparticles (Pd NPs) are used as signal markers. The abundant catalytic active sites and detection antibody (Ab2) binding sites rely on the double-shell hollow spheres to increase the specific surface area. The combined effect of Cu2O and Pd NPs can efficiently catalyze H2O2 to realize the amplification of electrical signals. The detection range of the immunosensor prepared by the above-mentioned sensing strategy was 50.0 fg ml−1 ∼ 100.0 ng ml−1, and the detection limit was 7.54 fg ml−1, which provides potential reference value for early clinical diagnosis.

Plasma S100β and neuron-specific enolase, but not neuroglobin, are associated with early cognitive dysfunction after total arch replacement surgery: A pilot study.

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.

Prognostic Value of Investigating Neuron-Specific Enolase in Patients with Ischemic Stroke.

The aim of the study was to assess the prognostic value of the plasma neuron-specific enolase (NSE) level as a predictor of functional outcome and motor function recovery in the acute period of ischemic stroke (IS).Materials and MethodsFifty patients with IS have been examined. On admission to the hospital and at 12–14 days after stroke onset, a clinical and neurological examination have been carried out with the supplementary quantitative assessment of neurological deficit severity according to the National Institutes of Health Stroke Scale (NIHSS), functional outcome according to the Modified Rankin Scale, and Rivermead Mobility Index. Enzyme immunoassay was used to determine NSE concentration in blood plasma in the acute period of the disease.ResultsThe NSE level in patients’ blood plasma in the first 48 h after stroke onset positively correlates with the ischemic focus volume (r=0.49; p=0.003) and the severity of neurological symptoms (according to NIHSS) (r=0.33; p=0.02). NSE less than 2 ng/ml in the acute disease period is a predictor of good functional outcome 12–14 days after stroke onset (OR=12.4; р=0.006). The NSE level >2.6 ng/ml is associated with a high likelihood of lethal outcome.Neurological deficit below 15 according to NIHSS as well as the NSE level <2 ng/ml in the acute IS period are estimated as prognostic factors of significant recovery of motor function at 2 weeks after disease onset (OR=5.8; р=0.02).ConclusionDetermination of NSE in blood plasma makes it possible to predict functional outcome of the disease development and the recovery of motor function in patients with IS.

Neuron-specific enolase concentrations for the prediction of poor prognosis of comatose patients after out-of-hospital cardiac arrest: an observational cohort study.

Neuron-specific enolase (NSE) is a biomarker for neurological outcomes after cardiac arrest with the most evidence collected thus far; however, recommended prognostic cutoff values are lacking owing to the discrepancies in the published data. The aim of the study was to establish NSE cutoff values for prognostication in the environment of a cardiac intensive care unit following out-of-hospital cardiac arrest (OHCA). A consecutive series of 82 patients admitted after OHCA were enrolled. Blood samples for the measurement of NSE levels were collected at admission and after 1 hour, 3, 12, 24, 48, and 72 hours. Neurological outcomes were quantified using the cerebral performance category (CPC) index. Each patient was classified into either the good (CPC ≤2) or poor prognosis (CPC ≥3) group. Median NSE concentrations were higher in the poor prognosis group, and the difference reached statistical significance at 48 and 74 hours (84.4 ng/ml vs 22.9 ng/ml at 48 hours and 152.1 ng/ml vs 18.7 ng/ml at 72 hours; P <0.001, respectively). Moreover, in the poor prognosis group, NSE increased significantly between 24 and 72 hours (P <0.001). NSE cutoffs for the prediction of poor prognosis after OHCA were 39.8 ng/ml, 78.7 ng/ml, and 46.2 ng/ml for 24, 48, and 72 hours, respectively. The areas under the curve were significant at each time point, with the highest values at 48 and 72 hours after admission (0.849 and 0.964, respectively). Elevated NSE concentrations with a rise in levels in serial measurements may be utilized in the prognostication algorithm after OHCA.

Changes of neuron specific enolase in serum of patients with silicosis

Objective: To explore the changes of neuron specific enolase (NSE) concentration in serum samples of patients with silicosis. Methods: In January 2020, 455 cases of silicosis diagnosed in Yantaishan Hospital from January 2018 to December 2019 were collected, and 60 healthy cases and 120 cases of lung cancer were selected as the healthy group and the lung cancer group. The serum levels of NSE were detected by chemical immunofluorescence assay and compared. Results: The serum NSE level of silicosis patients was [(22.88±7.86) ng/ml], higher than that of healthy group [(17.96±4.42) ng/ml] (P<0.05) . Serum NSE levels in the first, second and third stage silicosis groups were higher than those in the healthy group (P<0.05) , but there was no statistically significant difference between the silicosis groups at different periods (P>0.05) . The serum NSE level of silicosis patients was lower than that of the small cell lung cancer group (P<0.05) , but there was no statistically significant difference between silicosis group and non-small cell lung cancer group (P>0.05) . The area under curve of silicosis NSE was 0.718 (P<0.01) when the cut-off was 17.49 ng/ml, the sensitivity and specificity of NSE was 78% and 57% respectively. Conclusion: The serum NSE level of patients with silicosis is significantly increased, which can be used as an important reference index for the diagnosis and the differential diagnosis of silicosis.

Evaluation of cytokines and structural proteins to analyze the pathology of febrile central nervous system disease.

This study was designed to examine the pathophysiological differences in interleukin (IL) and structural protein levels between central nervous system (CNS) disorders associated with heat stroke and CNS stimulants. We measured the concentrations of IL-6, IL-8, neuron-specific enolase (NSE), and myelin basic protein (MBP) in blood and cerebrospinal fluid (CSF) from 87 autopsy cases. In addition, to examine changes in each marker, we cultured nerve cells at 40°C as a heat stroke model and administered 4-aminopyridine and ephedrine in cultured cells as a CNS stimulant model. IL-6 levels in blood and CSF were significantly higher in the stimulant compared with the heat stroke group. IL-8 levels in blood and CSF were relatively high in the stimulant, heat stroke, and psychotropic addiction groups. NSE levels in blood were high in the stimulant and heat stroke groups, while those in CSF were significantly higher in the heat stroke group. MBP levels in blood were markedly higher in the stimulant and heat stroke groups, but no differences were seen in CSF. Compared with the CNS stimulant model, the heat stroke model with cultured human nerve cells showed high values for each marker. The results of the autopsy and laboratory tests in the present cases and those of cultured cell experiments indicated that CNS disorders caused by CNS stimulants such as amphetamines led to changes in IL-6 as an immune response, which suggests that IL-8 may help protect nerve cells in cases involving heat stroke and stimulants.

Serum neuron-specific enolase: A promising biomarker of silicosis.

BACKGROUNDSilicosis is a type of chronic pulmonary fibrosis caused by long-term inhalation of silica dust particles. There has been no ideal biomarker for the diagnosis and differential diagnosis of silicosis until now. Studies have found that elevated neuron-specific enolase (NSE) concentration in the serum of silicosis patients is helpful for diagnosis and severity assessment of the disease. However, the number of cases in these studies was not enough to arouse attention.AIMTo investigate the clinical significance of serum NSE in the diagnosis and staging of silicosis.METHODSFrom January 2017 to June 2019, 326 cases of silicosis confirmed in Quanzhou First Hospital Affiliated to Fujian Medical University were included in the silicosis group. A total of 328 healthy individuals or medical patients without silicosis were included in the control group. Serum NSE concentrations of all subjects were determined by electrochemical luminescence.RESULTSThere were no significant differences in sex, age, smoking index and complications between the silicosis and control groups. The mean serum NSE concentration was 26.57 ± 20.95 ng/mL in the silicosis group and 12.42 ± 2.68 ng/mL in the control group. The difference between the two groups was significant (U = 15187, P = 0.000). Among the 326 patients with silicosis, 103 had stage I silicosis, and the mean serum NSE concentration was 15.55 ± 6.23 ng/mL. The mean serum NSE concentration was 21.85 ± 12.05 ng/mL in 70 patients with stage II silicosis. The mean serum NSE concentration was 36.14 ± 25.72 ng/mL in 153 patients with stage III silicosis. Kruskal–Wallis H test suggested that the difference in serum NSE concentration in silicosis patients in the three groups was significant (H = 130.196, P = 0.000). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.858 (95% confidence interval: 0.828-0.888; P = 0.000). When the NSE concentration was 15.82 ng/mL, the Jorden index was the largest, the sensitivity was 72%, and the specificity was 90%.CONCLUSIONSerum NSE concentration may be a promising biomarker for the diagnosis and assessment of severity of silicosis.

Propofol shows less negative effects on cognitive performances than dexmedetomidine in elderly intensive care unit patients.

Due to the improved clinical management of aging population and the consequently declined mortality among patients with critical illnesses, the number of survivors from intensive care units (ICUs) keeps rising. Studies to examine the association of cognitive impairment analgesic and sedation strategies would be beneficial to improve the quality of life of ICU survivors. A prospective clinical trial was designed to compare the effects of two drugs, propofol, and dexmedetomidine, on short-term cognitive impairment after sedation in elderly ICU survivors by evaluating the extent of independence limited by the dementia-related activities of daily livings (ADLs). The plasma concentrations of brain injury biomarkers including S100β and neuron-specific enolase (NSE) were determined using an enzyme immunoassay. There were 136 patients allocated into both the dexmedetomidine group and the propofol group, respectively, with matched demographic characteristics. The dementia scale of the patients in the dexmedetomidine group was significantly higher than the propofol group at weeks 1-4. Moreover, the changes in S100β and NSE concentrations in the dexmedetomidine group were significantly more pronounced than the propofol group. ICU patients who received dexmedetomidine intervention showed higher cognitive impairment than patients who received propofol, and this protective effect of propofol was not associated with the levels of brain injury markers S100β and NSE. Our study compared the effects of commonly used medications on short-term cognitive impairment in elderly ICU patients, which would aid the selection of sedation plan for the benefit of ICU patients.

Differential effect of ethanol intoxication on peripheral markers of cerebral injury in murine blunt traumatic brain injury.

BackgroundBlood-based biomarkers have proven to be a reliable measure of the severity and outcome of traumatic brain injury (TBI) in both murine models and patients. In particular, neuron-specific enolase (NSE), neurofilament light (NFL) and S100 beta (S100B) have been investigated in the clinical setting post-injury. Ethanol intoxication (EI) remains a significant comorbidity in TBI, with 30–40% of patients having a positive blood alcohol concentration post-TBI. The effect of ethanol on blood-based biomarkers for the prognosis and diagnosis of TBI remains unclear. In this study, we investigated the effect of EI on NSE, NFL and S100B and their correlation with blood–brain barrier integrity in a murine model of TBI.MethodsWe used ultra-sensitive single-molecule array technology and enzyme-linked immunosorbent assay methods to measure NFL, NSE, S100B and claudin-5 concentrations in plasma 3 hours post-TBI.ResultsWe showed that NFL, NSE and S100B were increased at 3 hours post-TBI. Interestingly, ethanol blood concentrations showed an inverse correlation with NSE but not with NFL or S100B. Claudin-5 levels were increased post-injury but no difference was detected compared to ethanol pretreatment. The increase in claudin-5 post-TBI was correlated with NFL but not with NSE or S100B.ConclusionsEthanol induces an effect on biomarker release in the bloodstream that is different from TBI not influenced by alcohol. This could be the basis of investigations into humans.

Relationship between YKL-40, neuron-specific enolase, tumor necrosis factor-a, interleukin-6, and clinical assessment scores in traumatic brain injury

Background and Objectives: The aim of the present study is to determine plasma and cerebrospinal levels of YKL-40, in combination with neuron-specific enolase (NSE), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and the clinical scales such as Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation a III, and MARSHALL classification in traumatic brain injury (TBI). Materials and Methods: This was a prospective study conducted on patient cohort of 27 patients with isolated severe TBI. Cerebrospinal fluid (CSF) and plasma were collected on the 24th and 96th h after trauma. CSF samples were obtained also from forensic autopsies of 29 adult healthy cadavers. Results: The CSF level of YKL-40 in TBI patients was higher compared to controls, while no significant change between CSF NSE levels in patients and controls was found. We determined a strong correlation between YKL-40 and NSE levels and TBI clinical assessment scores. The analysis of the influence of independent prognostic factors on the outcome of TBI patients showed that plasma NSE concentrations are the major independent variable which is associated with the survival of TBI patients. Still, changes in IL-6 and TNF-α levels could not be considered as reliable predictors of mortality. Conclusion: We present data for correlation of YKL-40 and NSE levels with clinical scores for assessment of trauma severity and the outcome of TBI patients. Even though further large-scale investigations are required to clarify and evaluate the clinical significance of both biomarkers, our findings suggest that YKL-40 and NSE might be implicated in the pathogenesis of TBI and could indicate the degree of neuroinflammation and brain damage.

Effects of Astragalus Polysaccharides Nanoparticles on Cerebral Thrombosis in SD Rats.

ObjectiveTo investigate the efficacy and improvement of Astragalus polysaccharides (APS) and APS-nano on cerebral thrombosis in rats.MethodsA total of 72 SD rats were randomly divided into NC group, Model group, APS-Nano group, and APS group. The cerebral thrombosis Model of SD rats was established by injecting compound thrombus inducer into the internal carotid artery. After 14 days of different intervention treatments, the TTC staining of brain tissue were performed, and A/left brain wet weight ratio, left brain/right brain wet weight ratio, blood rheology indexes, and coagulation function indexes of cerebral thrombosis were measured. ELISA was used to measure the contents of thromboxane 2 (TXB2), 6-keto-prostaglandin F1α (6-Keto-PGF1α), tissue factor (TF), neuron-specific enolase (NSE), S-100β, catenin (CAT), superoxide dismutase (SOD), as well as malondialdehyde (MDA). The binding specificity between miR-885-3p and TF was verified by the double-luciferin reporting experiment, and western blot was used to measure the expression level of TF protein.ResultsCompared with the Model group, after treatment with APS-nano or APS, the ratio of left brain/right brain wet weight decreased significantly. Whole blood low shear viscosity (WBLSV), whole blood high shear viscosity (WBHSV), plasma viscosity (PV), and erythrocyte aggregation index (Arbc) was all reduced. In addition, prothrombin time (PT) and activated partial thromboplastin time (APTT) were increased, and fibrinogen (FIB) content was decreased. The expression of TXB2, 6-Keto-PGF1α, and TF showed a downward trend. Similarly, the expression of TF protein was decreased. Furthermore, the contents of NSE and S-100β proteins were all decreased, whereas the contents of CAT and SOD were increased, and the contents of MDA was decreased. At the same dose, compared with APS treatment, APS-nano treatment had a significant inhibitory effect on cerebral thrombosis in rats. Finally, we found that TF is a target gene of miR-885-3p and specifically binds to miR-885-3p.ConclusionAPS has a significant inhibitory effect on the formation of cerebral thrombosis induced by compound thrombus inducers. Moreover, APS-nano has a more significant inhibitory effect on cerebral thrombosis. Meanwhile, the regulation of miR-885-3p regulating TF expression may be related to the occurrence of cerebral thrombosis.

The Combination of CA125 and NSE Is Useful for Predicting Liver Metastasis of Lung Cancer.

Purpose Liver metastasis is the final stage of cancer progression and is associated with poor prognosis. Although numerous indicators have been identified as having prognostic value for lung cancer and liver metastasis, liver metastases are still not diagnosed by imaging in many patients. To provide a more accurate method for clinical prediction of liver metastasis, we analyzed multiple factors to identify potential predictive factors for liver metastasis of lung cancer. Methods Patients first diagnosed with lung cancer between 2002 and 2016 (n = 1746) were divided into two groups, with and without liver metastasis. Serum concentrations of calcium, carcinoembryonic antigen (CEA), cancer antigen-125 (CA125), cancer antigen-153 (CA153), carbohydrate antigen-199 (CA199), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen (TPSA), and neuron-specific enolase (NSE) were analyzed in both patient groups. Results There was no significant difference in age or sex between the two groups. CA125 and NSE were significantly associated with liver metastasis. Compared with CA125, NSE was more specific, while it was less sensitive (P < 0.001). Further analysis of NSE concentrations was conducted in patients with non-small-cell lung cancer and indicated that NSE concentration differed significantly between those with and without liver metastasis (P = 0.023). We conducted analysis with NSE and CA125 combined, resulting in acceptable sensitivity (51.2%), specificity (72.6%), and area under the curve (0.64) values; sensitivity and area under the curve values were higher than those for individual factors, while specificity was higher than that for CA125. Conclusions The combination of CA125 and NSE can assist prediction of liver metastasis of lung cancer, providing improved diagnostic accuracy.

New diagnostic and prognostic biomarkers of the ischemic brain damage

Background . To determine the optimal approach to managing patients in the acute period of stroke, the search for biomarkers that can increase value of existing diagnostic methods continues. Objective : to clarify the significance of the levels of neuron-specific enolase (NSE), glial fibrillar acid protein (GFAP), NR2-antibodies in the blood serum (BS) of patients in the acute period of ischemic stroke (IS) in dynamics, determine their relationship with the severity of neurological disturbances and short-term outcome. Design and methods . 40 patients were examined in the acute period of IS, mean age 72.6 ± 1.9 years. The levels of biomarkers were determined in the BS in the first 72 hours of IS and on days 10–14. Results . The concentration of NSE and GFAP in patients with IS in the first 72 hours exceeded the reference values and significantly decreased by 10–14 days (34.9 ± 5.9 → 17.7 ± 1.1; p = 0.007 and 0.4 ± 0, 1 → 0.2 ± 0.005, p = 0.22 respectively). The level of NR2 antibodies did not exceed of the reference values (1.01 ± 0.3), and in dynamics, by 10–14 days, an increase in the indicator was noted (1.1 ± 0.3), p = 0.007. In patients with more severe symptoms, the concentration of NSE, GFAP and NR2 antibodies was higher by 10–14 days. Patients who had an unfavorable short-term outcome by 10–14 days had a higher level of NSE, GFKB and NR2 antibodies. Conclusion . The investigated substances can be used as biomarkers in IS to control the degree of damage to the brain tissue, monitor the worsening of the pathological process, as well as for prognostic purposes.

Predictive Value and Correlation of Neuron-Specific Enolase for Prognosis in Patients with Coma: A Systematic Review and Meta-Analysis

Objective: Coma is the most serious disturbance of consciousness, which affects the life quality of patients and increases the burden of their family. Studies to assess the prognostic value of neuron-specific enolase (NSE) in patients with coma have not led to precise, generally accepted prognostic rules. The study aims to assess the correlation between NSE and prognosis of coma and the predictive value of NSE for clinical prognosis. Methods: A search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data from the establishment time of databases to December 2019. This analysis included patients with coma, regardless of how long the coma was. In total, 26 articles were retrieved and included in the review. Results: The meta-analysis revealed the NSE concentration of patients with coma is significantly higher than that of the control group (standard mean difference = 0.88, 95% confidence interval [CI]: 0.63–1.12, p < 0.05). The pooled sensitivity and specificity of NSE in coma diagnosis was 0.5 (95% CI: 0.39–0.61) and 0.86 (95% CI: 0.71–0.94). Conclusions: The NSE concentration of patients with poor coma prognosis is significantly higher than that of the control group. The high NSE concentration is not necessarily a poor prognosis for coma, but low NSE concentration indicates a high probability of a good prognosis for coma.

Neuron-Specific Enolase Levels in Adults Under Venoarterial Extracorporeal Membrane Oxygenation

We aimed to determine if elevations in serum neuron-specific enolase are associated with brain injury and outcomes in adults who require venoarterial extracorporeal membrane oxygenation. Prospective observational study. Two ICUs of a university hospital, Paris, France. Consecutive adult patients treated with venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock or in-hospital refractory cardiac arrest. None. Serum sampled 1, 3, and 7 days after venoarterial extracorporeal membrane oxygenation cannulation was stored at -80°C and neuron-specific enolase concentrations were measured in batches at the end of the study. The association between neuron-specific enolase concentrations and outcomes (28-d mortality and poor outcome, defined by a score of 4-6 on the modified Rankin scale at 90 d) were explored by multivariable logistic regression, with neuron-specific enolase concentrations dichotomized according to median values. One-hundred three patients were included, of whom 26 (25%) received preextracorporeal membrane oxygenation cardiopulmonary resuscitation. Median (interquartile range) day-1, day-3, and day-7 neuron-specific enolase serum concentrations were 37 μg/L (26-51 μg/L), 25 μg/L (19-37) μg/L, and 22 μg/L (17-31 μg/L). After adjustment for Simplified Acute Physiology Score II, preextracorporeal membrane oxygenation cardiopulmonary resuscitation, and Sepsis Organ Failure Assessment score at time of cannulation, a day-3 neuron-specific enolase greater than 25 μg/L remained independently associated with 28-day mortality (adjusted odds ratio, 4.98; 95% CI, 1.86-13.32) and poor outcome at 90 days (adjusted odds ratio, 4.63; 95% CI, 1.81-11.84). A day-3 neuron-specific enolase threshold greater than 80 μg/L had a 100% specificity for prediction of both mortality (95% CI, 92-100%) and poor functional outcome (95% CI, 89-100%). In a subset of patients who underwent brain CT, neuron-specific enolase concentrations were significantly higher in patients diagnosed with stroke, as compared with those without stroke. In adult patients under venoarterial extracorporeal membrane oxygenation, day-3 serum neuron-specific enolase concentrations are independently associated with short-term mortality and poor functional outcomes. These findings deserve validation in a multicenter setting.

Predicting the prognosis for severe brain injury patients: short-latency somatosensory evoked potential combined with electroencephalogram reactivity

Objective: To explore the the effectiveness of using short-latency somatosensory evoked potential(SLSEP) combined with electroencephalogram(EEG) reactivity to predict the prognosis of severe brain injury(SBI) patients. Methods: Consecutive patients with SBI admitted in neurosurgery intensive care unit(NSICU) at Xiangya Hospital of Central South University from July 2018 to January 2019 were prospectively collected. SLSEP and EEG were recorded in these patients in NSICU within two weeks after injury onset. EEG reactivity(EEG-R) was tested during EEG signal stabilization. In addition, the concentrations of serum neuron-specific enolase (NSE) and S100 protein were also detected. All patients were evaluated with Glasgow Outcome Scale(GOS) during 12 months' follow-up. GOS grade 3 to 5 was defined as favorable group, and GOS grade 1 to 2 was defined as unfavorable group. The association of relevant predictors with patient's prognosis was assessed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate each potential predictor. Results: Forty-three patients were included in the study, with 26 patients of favorable outcomes and 17 patients with unfavorable prognosis. Univariate analysis revealed that the Glasgow Coma Scale (GCS) score, the concentration of serum NSE, EEG-R, the amplitude of SLSEP were all associated with the prognosis after 12 months' follow-up. Moreover, the AUC for prediction of favorable prognosis by GCS, NSE, EEG-R, SLSEP was 0.661(95%CI: 0.493-0.829), 0.697(95%CI: 0.531-0.862), 0.718(95%CI: 0.557-0.879) and 0.758(95%CI: 0.609-0.907) respectively. However, there was no significant difference of age, gender, pupillary light reflex and S100 protein between the two groups. Furthermore, multiple logistic regression analysis showed that only SLSEP amplitude (OR=2.058, 95%CI: 0.867-4.888) and EEG-R(OR=3.748, 95%CI: 0.857-16.394) were independent predictors of favorable prognosis, and the prognostic model containing these two variables yielded an predictive performance with an AUC of 0.798. Conclusion: The higher amplitude of SLSEP and the existence of EEG-R are predictors of good prognosis in SBI patients, and the combined use of SLSEP and EEG-R in predicting the prognosis of SBI patients is more reliable.

A Novel Diagnosis Method Based on Methylation Analysis of SHOX2 and Serum Biomarker for Early Stage Lung Cancer.

Objectives:Lung cancer (LC) is often accompanied by significant methylation abnormalities. This study aimed to develop a decision tree (DT) accompanied the stature homeobox 2 gene (SHOX2) / prostaglandin E receptor 4 (PTGER4) gene DNA methylation with traditional tumor marker in the differential diagnosis of benign and malignant lung nodule.Methods:We performed a study with 104 patients enrolled in the LC group and 36 patients in the benign lung diseases group. All the clinical data of these patients were collected through electronic medical record. Total Methylation (TM) status of both SHOX2 and PTGER4 was defined as methylation levels of SHOX2 plus methylation levels of PTGER4. One-way analysis was used to compare the concentrations of serum samples and t-test was used to compare pairwise mean values between groups. Receiver operating curve (ROC) was used to evaluate the diagnostic value. Furthermore, the strategy was validated in 19 LC patients and 11 patients with benign lung diseases.Results:There were significant differences between the concentration of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21 -1) and the methylation levels of SHOX2, PTGER4 and TM in lung benign diseases and cancer group. The AUCs of NSE, CEA, CYFRA21 -1, Methylation SHOX2, Methylation PTGER4 and TM were 0.721 (95% CI: 0.627–0.816), 0.753 (95% CI: 0.673–0.833) and 0.778(95% CI: 0.700–0.856), 0.851(0.786-0.916), 0.847(0.780-0.913) and 0.861(0.800-0.922) respectively. We developed a DT model with TM and CYFRA21 -1 used in this study, and the area under the curve (AUC) of DT was 0.921 and the sensitivity up to 0.856. In the validation cohort, the AUC of SHOX2, PTGER4 and TM was also much higher than traditional serum markers.Conclusions:Our results indicated that the DT model calculated from the TM and CYFRA21 -1 can accurately classify LC and benign diseases, which showed better diagnostic performance than traditional serum parameter.

Exploration and analysis of the value of tumor-marker joint detection in the pathological type of lung cancer

Lung cancer is a disease characterized by the uncontrolled growth of cells in lung tissue. If left untreated, cell growth can spread beyond the lungs to a process called metastasis and reach surrounding tissues or other organs. This experiment was set up to discuss and analyze the research value of joint detection of tumor markers including carcino-embryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in the diagnosis and pathological type of lung cancer. From November 2016 to February 2018, 378 cases of patients with lung cancer treated in our hospital and 200 cases of people with healthy physical examinations were collected. The electrochemical immunoluminescence method was adopted to detect the CEA, CYFRA21-1 and NSE. The detected positive rate and the concentration of CEA, CYFRA21-1 and NSE of lung cancer group were higher than that of the healthy physical examination group. The differences were of statistical significance (P&lt;0.05); the detected positive rate of CEA and CYFRA21-1 and the concentration of CEA, CYFRA21-1 and NSE of squamous carcinoma group were higher than that of the adenocarcinoma group. The differences were of statistical significance (P&lt;0.05). The CEA, CYFRA21-1 and NSE are related to the pathological type of lung cancer and can be regarded as related indicators to diagnose lung cancer.

Neuroinflammatory Biomarkers Associated With Mild Traumatic Brain Injury History in Special Operations Forces Combat Soldiers

Special Operations Forces (SOF) combat soldiers are frequently exposed to blast and blunt neurotrauma, most often classified as mild traumatic brain injury (mTBI). Repetitive mTBI may increase the risk of developing long-term neurological sequelae. Identifying changes in neuroinflammatory biomarkers before chronic conditions emerge could serve as preliminary evidence of developing neuropathology. To determine the effects of mTBI history, lifetime mTBI incidence, and recency on blood biomarker concentrations of axonal protein neurofilament light (NfL), glycolytic enzyme neuron-specific enolase (NSE), astrocyte-expressed S100 calcium-binding protein B (S100B), and neurotrophic cytokine interleukin-6 (IL-6) in healthy, active duty SOF combat soldiers. Self-reported mTBI history/recency and fasted blood samples were collected in this cross-sectional study of 104 asymptomatic SOF combat soldiers. Biomarker concentrations were quantified using commercial enzyme-linked immunosorbent assays. Mann-Whitney U and Kruskal-Wallis tests were used to compare groups. Post hoc tests with appropriate corrections were conducted as warranted. Soldiers with mTBI history had higher NSE concentrations than those without (z = -2.60, P = .01). We also observed significant main effects of lifetime mTBI incidence on NSE (χ(3) = 9.52, P = .02) and S100B (χ(3) = 8.21, P = .04) concentrations and a significant main effect of mTBI recency on NfL concentration (χ(2) = 6.02, P = .049). The SOF combat soldiers with mTBI history had increased NSE. Longitudinal studies in this population are needed due to between-subject heterogeneity in biomarker concentrations. The NfL concentrations in our SOF combat soldiers-regardless of mTBI history or recency-were similar to values previously reported in civilian acute TBI patients.