Serum NSE Research Articles

Effect of Polydatin on Neurological Function and the Nrf2 Pathway during Intracerebral Hemorrhage.

This study investigates the effect of polydatin on the neurological function of cerebral hemorrhage rats and on the Nrf2 pathway of the endogenous antioxidant system in tissues around cerebral hematoma. Further, the study also aims to provide solid insights for clinical diagnosis and treatment. A total of 54 SPF grade male Wistar rats were divided into three groups: the sham group, model group, and polydatin group. Various parameters such as neurological deficit score, brain water content, pathological morphology, oxidative stress index content, Nrf2, NQO1, HO-1 mRNA expression, and the expression of HO-1, Nrf2, and kelch-like epichlorohydrin-1 (Keap1) protein were observed. Compared with the sham group, the mNSS score and brain water content of rats in the model group increased significantly after dosing (P < 0.05). When compared with the model group, the mNSS score and brain water content of rats in the polydatin group decreased significantly after dosing (P < 0.05). Compared with the other group, the serum NSE content of rats in the polydatin group decreased (P < 0.05). An increase was observed in the contents of NO, SOD, MDA, GSSG, and GSH in the brain tissue of rats in the model group when compared with the sham group. Compared with the model group, the contents of NO and MDA in the brain tissue of rats in the polydatin group decreased, while the contents of SOD, GSSG, and GSH increased (P < 0.05). The relative expressions of Nrf2, NQO1, and HO-1mRNA in the brain tissue of rats in the polydatin group was relatively high compared with both groups (P < 0.05). Polydatin can improve the neurological function of ICH rats and reduce the oxidative stress response by regulating the Nrf2-ARE pathway and downstream gene expression. This study preliminarily discussed the relevant mechanism of polydatin in the treatment of ICH rats, thus providing a theoretical reference to ICH treatment.

Successful Therapy on Patients with Yolksac and Embrional Carcinoma by Surgery and Chemotherapy

Background: Malignant mixed germ cell tumors account for 13-25% of all non seminoma germ cell tumors, almost all cases were found in males (85%), increased in the third decade, and had an average survival rate of 40-45%. With modern management the average 5-year survival rate can be over 80%.Case Report: We reported a case report in Saiful Anwar Malang Hospital, Indonesia, a young man, 26 years old with an malignant epithelial tumor derived from mediastinal or lung. The CT scan of the chest showed an lobulated solid mass of iso-hipodens on the anterior superior mediastinum, mass encompassing the aortic arch, left pulmonalis artery, subclavian artery. The result from transthoracic FNAB with USG guidance showed an malignant epithelial tumor derived from mediastinal or lung, impression of an adeno squamous carcinoma. The AFP, LDH, and NSE serum level was elevated. Patient underwent a surgical sternotomy and tumor debulking. The biopsy showed an malignant mixed germ cell tumor (yolksac and embrional carcinoma). These were confirming the diagnosis of malignant mixed germ cell mediastinal tumor (yolksac and embrinonal carcinoma). Patient received a combination bleomycin, etoposid, cisplatin 3 series chemoteraphy  and evaluated.Conclusion: Some procedures like biopsy, tumor marker, could differentiate the subtype of mediastinal germ cell tumor. The multimodality treatment by combining surgical therapy (surgical sternotomy and tumor debulking) with chemotherapy could increase the survival rate of patients.

Diagnostic Value of Serum Biomarkers for Differentiating Central and Peripheral Causes of Acute Vertigo.

Background: In patients presenting with acute vertigo or dizziness, distinguishing central from peripheral is a diagnostic challenge. This study investigated potential serum markers for differentiating central and peripheral vertigo in patients with acute-onset vertigo.Methods: This prospective case–control study recruited consecutive participants from the Emergency Department, including patients with acute-onset vertigo or dizziness within 12 h and control subjects. We used enzyme-linked immunosorbent assays to measure the serum S100β, NSE, BDNF, GFAP, and IL-6 levels during the acute period.Results: The 114 study subjects included 28 patients with central vertigo (CV), 49 patients with peripheral vertigo (PV), and 37 age- and sex-matched healthy controls. No differences were found in risk factor distribution among the three groups. In patients with CV, the serum NSE and S100β levels were significantly (p < 0.05) elevated compared with the control and PV groups. The ROC analysis gave an AUC of 0.843 (95% CI = 0.753–0.932) for NSE and 0.787 (95% CI = 0.687–0.886) for S100β for predicting CV. However, there were no significant differences in the serum GFAP and BDNF levels among the CV, PV, and control groups.Conclusions: Serum NSE and S100β levels are significantly higher in patients with CV, such as occurs with posterior circulation ischemic stroke or vertebrobasilar insufficiency. S100β and NSE may serve as serum biomarkers for differentiating between CV and PV in patients with acute-onset vertigo.

Analysis of serum S-100 beta protein, NSE and neurological deficits in patients with cerebral infarction and reperfusion treated with butylphthalide

Objective To investigate the effects of butylphthalide on serum S-100 beta protein, NSE and neurological deficits in patients with cerebral infarction and reperfusion. Methods From January 2016 to January 2018, 104 patients with early cerebral infarction admitted to the People's Hospital of Feicheng were divided into two groups according to different treatment methods.The control group (n=52) was given routine treatment, while the observation group (n=52) was given butylphthalide treatment on the basis of the control group.The degree of neurological deficit, serum NSE and S-100 beta protein levels were compared between the two groups before and after thrombolysis. Results The NIHSS scores of the two groups before thrombolysis were (10.27±1.32)points and (10.28±1.30)points, respectively, the difference between the two groups was no statistically significant(t=0.038, P>0.05). The NIHSS scores of the two groups were decreased at 24h and 7d after thrombolysis, which of the observation group at 24h and 7d after thrombolysis were (8.32±1.37)points and (4.25±1.54)points, respectively, which were significantly lower than those of the control group [(9.24±1.40)points and (9.50±1.24)points], the differences were statistically significant (t=3.396, 19.147, all P 0.05). At 24h and 7d after thrombolysis, the serum NSE levels of the two groups were decreased.The serum NSE levels of the observation group at 24h and 7d after thrombolysis were (15.08±9.35)U/mL and (13.25±6.47)U/mL, respectively, which were significantly lower than those in the control group [(18.96±10.14)U/mL and (16.98±7.11) U/mL], the differences were statistically significant (t=2.028, 2.79, all P 0.05). At 24h and 7d after thrombolysis, the serum S-100β protein levels were decreased in both two groups, which in the observation group were (1.13±0.62 )μg/L and (0.53±0.48)μg/L, respectively, which were significantly lower than those in the control group [(1.40±0.64)μg/L, (0.87±0.32)μg/L], the differences were statistically significant (t=2.185, 4.25, all P<0.05). Conclusion Butylphthalide injection for patients with cerebral infarction and reperfusion can effectively promote the recovery of neurological function, improve the levels of serum NSE and S-100 beta protein, and help patients recover as soon as possible. Key words: Infarction, middle cerebral artery; Reperfusion; Serum S-100 beta protein; NSE; Neurological deficit; Butylphthalide

Prognostic role of EEG identical bursts in patients after cardiac arrest: Multimodal correlation

AimsEEG burst-suppression (BS) heralds poor outcome after cardiac arrest (CA). Within this pattern, identical bursts (IB) have been suggested to be absolutely specific, in isolation. We assessed IB prevalence and their added predictive value for poor outcome in a multimodal prognostic approach. MethodsWe retrospectively analyzed a registry of comatose adults with CA (April 2011–February 2019), undergoing EEG at 5–36 h and 36–72 h. SB and IB were visually assessed. Cerebral Performance Categories (CPC) at 3 months were dichotomized as “good” (CPC 1–2), or “poor” (CPC 3–5). Sensitivity, specificity, positive, negative predictive values of BS and IB for poor outcome were calculated. A multimodal prognostic score was created assigning one point each to unreactive and epileptiform EEG, pupillary light reflex and SSEPs absence, NSE > 75 μg/l. In a second score, IB were added; predictive performances were compared using Receiver Operating Characteristic (ROC) curves. ResultsOf 522 patients, 147 (28%) had BS in any EEG (10 [7%] had good outcome and 129 [88%] died). Of them, 53/147 (36%, 10% of total) showed IB, 47/53 (89%) of which within 36 h. IB were 100% specific for poor outcome, and associated with higher serum NSE than BS. However, there was no significant difference between the scores with and without IB for CPC 3–5 (p = 0.116). ConclusionIB occur in 10% of patients after CA. In our multimodal context, IB, albeit being very specific for poor outcome, seem redundant with other predictors.

Diagnostic Value and Clinical Significance of Combined Detection of Serum Markers CYFRA21-1, SCC Ag, NSE, CEA and ProGRP in Non-Small Cell Lung Carcinoma.

The aim of the study is to explore the diagnostic value and clinical significance of combined detection of serum markers CYFRA21-1, SCC Ag, NSE, CEA and ProGRP in non-small cell lung cancer. CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP levels of 113 patients with lung cancer, 110 patients with benign lung diseases, and 90 healthy volunteers were detected by electrochemiluminescence assay. The correlations between positive expressions and clinical and pathological parameters were analyzed. The diagnostic values of CYFRA21-1, SCC, NSE, CEA, and ProGRP were evaluated by plotting ROC curves. The positive expression rates of CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP in the lung cancer group significantly exceeded those of benign lung disease and healthy groups (p < 0.05). In the lung cancer group, CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP levels significantly varied in patients with different degrees of invasion and clinical stages in the presence/absence of lymph node metastasis (p < 0.05). AUCs of diagnosis by CYFRA21-1, ProGRP, CEA, SCC Ag, and NSE were 0.737 [95% CI (0.582 - 0.893)], 0.829 [95% CI (0.742 - 0.915)], 0.848 [95% CI (0.739 - 0.956)], 0.758 [95% CI (0.642 - 0.874)], and 0.857 [95% CI (0.764 - 0.951)], respectively, with the optimal cutoff values of 11.38 µg/mL, 103.47 pg/mL, 5.78 ng/mL, 3.92 ng/mL, and 13.36 ng/mL, respectively. The combined diagnostic sensitivity and accuracy both exceeded those based on individual markers, but the combined diagnostic specificity was slightly lower than those using CYFRA21-1, SCC Ag, and ProGRP alone. CYFRA21-1, SCC Ag, NSE, CEA, and ProGRP levels of patients with lung cancer increased abnormally. The combined detection effectively improved diagnostic accuracy and sensitivity.

Neuron-specific Enolase Level after the Onset of Delayed Neurological Sequelae with Acute Carbon Monoxide Intoxication

Background: Delayed neurological sequelae (DNS) is a major problem in carbon monoxide (CO) intoxication. Many other studies have showed whether serum NSE of acute phase can predict DNS in CO poisoning. However, no study has examined NSE levels after development of DNS. Therefore, we report serum NSE levels after the onset of DNS. Case presentation: We described the NSE levels in two cases of DNS. The first was a 33-year-old woman who presented with concentration problems 39 days after CO exposure. The second was a 51-year-old woman who presented with gait disturbance and urinary incontinence 23 days after CO exposure. Brain magnetic resonance imaging (MRI) and NSE levels were obtained in both patients. Brain MRI confirmed brain injury and the diagnosis of DNS was made. The NSE levels of the two patients were 12.51 and 16.18 ng/mL, respectively. Conclusion: Although the initial NSE elevated level may be useful in the prediction of carbon monoxide induced DNS, it may be decreased to normal reference range after the onset of DNS.

Diagnostic value of serum NSE, S100B protein and myocardial zymogram in premature infants with intrauterine infection

Objective To explore the diagnostic value of serum NSE, S100B protein and myocardial zymogram in premature infants with intrauterine infection. Methods From January 2016 to December 2017, 60 preterm infants with intrauterine infection in the Integrated Chinese and Western Medicine Hospital of Wenzhou were selected in the study.According to whether brain injury occurred, they were divided into brain injury group (28 cases) and non-brain injury group (32 cases). Serum NSE content was detected by chemiluminescence method, serum S100B protein level was detected by enzyme linked immunosorbent assay (ELISA), and serum CK and HBDH levels were detected by automatic biochemical analyzer.The serum levels of NSE, S100B, CK and HBDH were compared between the two groups, the combined diagnostic efficacy of NSE+ S100B protein+ CK+ HBDH was analyzed, the correlation of serum NSE, S100B protein, CK, HBDH with brain injury wasanalyzed. Results The levels of serum NSE [(2.43±0.54)μg/L] and S 100B [(14.36±3.21)ng/L] in the brain injury group were higher than those in the non-brain injury group [(0.97±0.27)μg/L and (8.10±1.87)ng/L] (t=13.498, 9.370, all P<0.05). The levels of serum CK [(437.64±54.12)U/L] and HBDH [(387.91±56.45)U/L] in the brain injury group were significantly higher than those in the non-brain injury group [(183.54±32.58)U/L and (174.3±26.63)U/L] (t=22.347, 19.126, all P<0.05). The sensitivity and specificity of the combined diagnosis of NSE+ S100B protein and myocardial zymogram were higher than those of each single index.Serum NSE, S100B protein, CK and HBDH were positively correlated with brain injury. Conclusion The elevation of serum NSE, S100B protein and myocardial zymogram in preterm infants with intrauterine infection after birth has certain clinical significance in judging whether brain injury occurs or not. Key words: Intrauterine infection; Premature infants; Brain injury; Neuron-specific enolase; S100B protein; Creatine kinase; Carboxybutyrate dehydrogenase; Early diagnosis

Abstract 23: The Usefulness of Neuron-Specific Enolase in Cerebrospinal Fluid to Predict Neurological Prognosis in Cardiac Arrest Survivors Who Underwent Target Temperature Management: A Prospective Observational Study

Aim: We aimed to investigate the prognostic performance between serum NSE and cerebrospinal fluid (CSF) NSE for 6-month neurologic outcome in OHCA survivors underwent target temperature management (TTM). Hypothesis: We hypothesized that the NSE levels measured in the CSF would affect the change, earlier and more sensitively than serum, according to severity of hypoxic brain damage. Methods: This single-centre prospective observational study included out-of-hospital cardiac arrest (OHCA) patients underwent TTM. NSE levels were assessed in blood and CSF samples obtained immediately (Day 0), and 24 h (Day 1), 48 h (Day 2), and 72 h (Day 3) after return of spontaneous circulation (ROSC). The primary outcome was the 6-month neurological outcome. Results: We enrolled 34 patients (males, 24; 70.6%), 16 (47.1%) had a poor neurologic outcome. CSF NSE and serum NSE values were significantly higher in the poor outcome group compared to the good outcome group at each time point, except for serum Day 0. CSF NSE and serum NSE had area under curve (AUC) of 0.819-0.972 and 0.648-0.920, respectively. CSF NSE prognostic performances were significant higher than serum NSE at Day 1 and showed excellent AUC values (0.969; 95% Confidential Interval [CI] 0.844-0.999) and high sensitivity (93.8%; 95% CI 69.8-99.8) at 100% specificity. Conclusion: We found CSF NSE values were highly predictive and sensitive markers of 6-month poor neurological outcome in OHCA survivors treated with TTM at Day 1 after ROSC. Thus, CSF NSE level at day 1 after ROSC can be a useful early prognosticator in OHCA survivors.

Hippocampal neuronal ferroptosis involved in cognitive dysfunction in rats with sepsis-related encephalopathy through the Nrf2/GPX4 signaling pathway

To evaluate the effects of ferroptosis in hippocampal neurons on cognitive dysfunction in rats with sepsis-associated encephalopathy (SAE) and its potential molecular mechanisms. (1) Screening experiment of SAE modeling conditions: 42 healthy male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group (n = 6) and lipopolysaccharide (LPS) 5, 15, 30 mg/kg groups (each n = 12) according to the random number table method. The SAE modeling conditions were determined by survival and the changes in mean arterial pressure (MAP) and heart rate (HR) within 72 hours, the percentage of stiffness status, the levels of serum inflammatory factors including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), neuron specific enolase (NSE, a marker of neuronal injury), serum iron and lactic acid (Lac) contents, and the morphological changes in CA1 of hippocampus after 72 hours. (2) Deferoxamine (Def) intervention experiment: according to the results of screening experiments, 28 healthy male SD rats were divided into NS control group (n = 8), SAE group (n = 10) and Def+SAE group (n = 10) according to the random number table method. In the Def+SAE group, 100 mg/kg Def was injected intraperitoneally 12 hours before the modeling, once every 12 hours, with a total of 7 times; the rats in the NS control group and SAE group were injected with the same amount of NS. Then the cognitive function of rats was evaluated by fear conditioning test for the percentage of stiffness status; serum IL-6, TNF-α and NSE levels were determined by enzyme-linked immunosorbent assay (ELISA); the levels of serum Lac, serum iron and hippocampal malondialdehyde (MDA) and iron contents were determined by chemical colorimetric; the protein expressions of nuclear factor E2 related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and NAPDH oxidase 1 (NOX1) in hippocampus were determined by Western Blot; morphological changes in hippocampal CA1 were observed after hematoxylin and eosin (HE) staining. (1) Compared with the NS control group, intraperitoneal injection of 15 mg/kg LPS could significantly reduce the MAP and HR as time prolonged, and the reduction was most significant at 72 hours. The 72-hour survival rate was significantly reduced and cognitive function was impaired. The levels of serum IL-6, TNF-α, Lac and NSE were increased while the serum iron content was decreased significantly. The morphology of vertebral cells in hippocampal CA1 was irregular and some of the cells were obviously vacuolated. In the LPS 5 mg/kg group, there were no significant changes in vital signs, inflammation, organ function or cognitive dysfunction, while the symptoms of septic shock were apparent in the LPS 30 mg/kg group. Therefore, SAE model was reproduced by intraperitoneal injection of 15 mg/kg LPS for 72 hours. (2) Compared with the NS control group, the percentage of stiffness in the SAE group was significantly reduced. The levels of serum IL-6, NSE and hippocampal MDA, iron were significantly increased. The serum iron contents and hippocampal Nrf2 and GPX4 protein expressions were significantly reduced, while the hippocampal NOX1 protein expression was significantly increased. The morphology of vertebral cells in hippocampal CA1 was irregular and the cytoplasm was deeply stained. The results indicated that the level of oxidative stress in the hippocampus of SAE rats was increased, the neuron degenerations were obvious, and the cognitive function of rats were impaired. Compared with the SAE group, the percentage of stiffness in the Def+SAE group was significantly increased [(63.4±6.4)% vs. (47.6±6.0)%, P < 0.05]. The levels of serum IL-6, NSE, iron and hippocampal MDA, iron were significantly reduced [serum IL-6 (ng/L): 73.14±8.31 vs. 99.86±12.37, serum NSE (μg/L): 3.67±0.51 vs. 5.92±0.79, serum iron (mg/L): 68.43±8.12 vs. 134.60±15.63, hippocampal MDA (mol/g): 4.62±0.90 vs. 6.62±0.84, hippocampal iron (μg/g): 155.32±17.86 vs. 221.54±27.54, all P < 0.05]. The hippocampal protein expressions of Nrf2 and GPX4 were significantly increased [Nrf2/β-actin: 0.41±0.07 vs. 0.18±0.03, GPX4/β-actin: 0.74±0.09 vs. 0.40±0.06, all P < 0.05] while the hippocampal NOX1 protein expression was significantly reduced (NOX1/β-actin: 0.62±0.08 vs. 1.11±0.16, P < 0.05). The vertebral cells was significantly improved as compared with the SAE group. These findings showed that the oxidative stress level in hippocampus of the Def+SAE group was reduced, neuron degeneration was significantly alleviated, and the cognitive function of the rats was significantly improved. The cognitive function of rats with SAE was significantly impaired, the hippocampal neurons were obviously damaged and ferroptosis was increased. Def pretreatment could significantly reduce iron deposition and ferroptosis in hippocampal neurons of SAE rats and improve cognitive dysfunction, which may be related to activation of Nrf2/GPX4 signaling pathway.

Effect of Shuxuening combined with edaravone on neurological function, serum VEGF and serum sVCAM-1 in patients with cerebral infarction

Objective To investigate the effects of Shuxuening injection combined with edaravone on neurological function, serum vascular endothelial growth factor (VEGF) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with cerebral infarction. Methods A total of 112 patients with cerebral infarction admitted to Zhejiang Provincial Armed Police Hospital from August 2016 to August 2018 were enrolled in the study.They were divided into observation group and control group according to the digital table, with 56 patients in each group.The two groups were given routine symptomatic treatment.On the basis of this, the control group was given edaravone treatment, and the observation group was given Shuxuening injection combined with edaravone.The changes of NIHSS, GCS score, serum NSE, NGF, NTF, VEGF and sVCAM-1 levels before and after treatment were compared between the two groups, and the clinical efficacy was compared. Results After treatment, the effective rate of the observation group was 92.86%(52/56), which was higher than that of the control group 73.21%(41/56), the difference was statistically significant (χ2=7.669, P<0.05). After treatment, the NIHSS score, NSE, sVCAM-1 of the two groups were decreased, which of the observation group were lower than those of the control group[(3.27±1.16)points vs.(6.32±2.12)points, (13.15±1.14)μg/L vs.(17.64±1.89)μg/L, (648.56±134.67)ng/mL vs.(1 078.36±131.23)ng/mL], while the GCS score, NGF, NTF, VEGF levels of the two groups were elevated, which of the observation group were higher than those of the control group[(13.64±3.86)points vs.(11.89±3.41)points, (76.13±8.72)μg/L vs.(68.24±7.25)μg/L, (5.14±0.36)μg/L vs.(3.74±0.29)μg/L, (831.51±91.67)ng/L vs.(752.83±91.24)ng/L], the differences were statistically significant (t=9.414, 2.543, 15.223, 5.205, 22.663, 4.552, 15.672, all P<0.05). Conclusion Shuxuening injection combined with edaravone can improve the curative effect of patients with cerebral infarction, improve neurological function, effectively improve serum VEGF level and decrease sVCAM-1 level.It is worthy of clinical application. Key words: Infarction, middle cerebral artery; Central nervous system; Vascular endothelial growth factors; Shuxuening; Edaravone

NSE & S100B protein blood level assessment during a long-distance trail race.

Blood samples were collected from 4 athletes before, during and at the end of one of two races: Grand Raid de la Réunion 2017 (GRR: 165 km, elevation gain: 9529 m, 2 runners) and Trail de la Bourbon 2017 (TB: 111 km, elevation gain: 6433 m, 2 runners). Serum S100B and NSE levels were measured for each runner before, during and after the race. Serum S100B levels (normal range: < 0.15 μg/L) increased early during the race and remained high up to the end of the race in all 4 runners (range: 0.17-0.59 μg/L). NSE level (normal range: < 15 μg/L) increased in 3 of the 4 runners (range: 16.8-39.2 μg/L). This preliminary study shows the potential interest of S100B and NSE serum assessment during long-distance races. Further studies are needed to confirm these results and to investigate the origins and significance of this increase in brain injury markers.

The Application Value of Serum HE4 in the Diagnosis of Lung Cancer.

Background:To investigate the clinical value of HE4 detection in the diagnosis of lung cancer and the clinical significance of combined detection with CEA, NSE and CYFRA21-1. Methods:90 cases of lung cancer, 30 cases of pulmonary tuberculosis, 30 cases of pneumonia and 30 cases of health physical examination were selected. The levels of serum HE4, CYFRA21-1, CEA and NSE were detected by electrochemiluminescence method. Statistical analysis was performed to observe the sensitivity and specificity. Results:The levels of serum HE4, CEA, NSE and CYFRA21-1 in lung cancer group were significantly higher than those in tuberculosis group and health physical examination group. There was no significant difference in the levels of HE4, CEA and NSE between the lung cancer group and the pneumonia group, the difference of CYFRA21-1 level was statistically significant (p<0.05).With health physical examination group as normal controls, the sensitivity and specificity of combined detection of HE4, CEA, NSE and CYFRA21-1 in the diagnosis of lung cancer were 82.2% and 90.0%,and the area under the curve (AUC) was 0.907, followed by HE4 (0.867), CYFRA21-1 (0.787), CEA (0.752) and NSE (0.747). Conclusion: HE4 can be used as a serological marker for the diagnosis of lung cancer. The combined detection of HE4, CEA, NSE and CYFRA21-1 can improve the diagnosis of lung cancer. Serum HE4 levels are highly specific in distinguishing between lung cancer patients and normal population, and are equivalent to CYFRA21-1; but they are less specific than CYFRA21-1 in distinguishing lung cancer patients from pneumonia patients.

Cambio en la enolasa neuroespecífica de los supervivientes de parada cardiorrespiratoria extrahospitalaria: herramienta útil para predecir el pronóstico neurológico

Introduction and objectivesNeuron-specific enolase (NSE) is a prognostic marker in out-of-hospital cardiopulmonary arrest (OHCA) survivors treated with mild therapeutic hypothermia (MTH). The objectives were to analyze the correlation between dynamic changes in NSE and outcomes and to determine the measurement timing that best predicts neurological status. MethodsMulticenter cohort study including patients admitted after shockable rhythm OHCA and treated with MTH. Serum NSE was sampled at 2 different times and Δ-NSE (%) was calculated as 100 x (NSE2-NSE1)/NSE1. In-hospital mortality and neurological outcome, as assessed by the Cerebral Performance Category (CPC) scale, were evaluated during admission and after a 6-month follow-up. ResultsWe included 166 patients admitted to 4 hospitals. In-hospital mortality was 31.9%. Almost 60% of patients had a good neurological recovery (CPC 1-2). On univariate and multivariate logistic regression analyses, an increase in NSE levels was associated with higher in-hospital mortality and worse CPC on discharge and after 6-months (P<.001). Positive Δ-NSE showed an OR=9.28 (95% CI 4.40-19.57) for mortality, OR=11.23 (95% CI 5.24-24.11) for CPC 3-5 at discharge and OR=11.14 (95% CI 5.05-24.55) for CPC 3-5 after 6-months’ follow-up (P<.001). The first NSE measurement, conducted at 18 to 24hours, and the second measurement at 69 to 77hours after OHCA showed a high area under the curve in predicting CPC at discharge (0.9389 and 0.9909, respectively; 0.8096 for the whole cohort). ConclusionsDynamic changes in NSE serum levels are good markers of hard clinical outcomes after an OHCA due to shockable rhythm in an MTH-treated cohort. NSE measurements at specific intervals after OHCA may predict events even more precisely.

Comparative Effects of Monosialoganglioside versus Citicoline on Apoptotic Factor, Neurological Function and Oxidative Stress in Newborns with Hypoxic-Ischemic Encephalopathy.

To determine the comparative effect of monosialoganglioside versus citicoline on the content changes of serum apoptotic factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-β and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) in newborns with hypoxic-ischemic encephalopathy (HIE). An experimental study. Emergency Department, Affiliated Children's Hospital of Zhengzhou University, China, from October 2016 to February 2018. A total of 90 newborns with HIE were randomly divided into a treatment group and a control group, with 45 cases in each group. In addition to the conventional treatment, the treatment group was given monosialoganglioside treatment, while the control group was given citicoline treatment. Both groups were treated for 10 days. After treatment, the content differences of serum apoptosis factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-β and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) were observed in the two groups. After treatment, the levels of serum PDCD5, sFas, sFasL, MDA, NSE and S100-β in the treatment group were lower than those in the control group (all p<0.001). The contents of serum SOD, GSH-PX, BDNF and NGF in the treatment group were higher than those in the control group (all p<0.001). Monosialoganglioside can effectively improve the apoptotic factors, neurological function and oxidative stress indices in newborns and maintain the stability of the internal environment, so it is worthy of promotion and application.

Value of serum neuroendocrine markers in evaluation of neuroendocrine prostate cancer: A validation study using metastatic biopsies.

278 Background: NEPC, de novo or treatment-related in late stage CRPC, is a distinct entity with poor prognosis. Developing non-invasive methods for detection of NEPC is important for clinical practice and trial enrollment. We previously reported on the clinical and genomic characterization of NEPC (Conteduca et al ESMO 2018). A separate study (Aggarwal et al JCO 2018) suggested that low levels of NSE and CgA were associated with a strong NPV for NEPC on biopsy (bx). This study aimed to validate the utility of NSE and CgA in evaluation of NEPC by comparison with met bx. Methods: Our IRB-approved NEPC database was screened for pts who underwent met bx and had concurrent serum NSE, CgA. Clinical data, serum PSA, LDH, ALP, Hb were recorded at time of bx. Comparison of continuous variables between CRPC adeno and NEPC was assessed by nonparametric Kruskal-Wallis test. ROC curve analysis was performed for evaluation of predictive models with serum NE markers. Results: 152 men were identified, median age 71 yrs (49-97). 35 pts had pure/mixed NEPC, while the rest (N=117) had typical adenoca on bx. Half of pts (80/152, 52.6%) received abiraterone or/and enzalutamide. Liver mets were more common in NEPC pts (P=0.001). Median serum NSE (11.2 vs 8.6 ng/mL, P=0.008) and CgA (211 vs 135 ng/mL, P=0.035) were higher in pts with NEPC vs CRPC adeno (Table). Using ROC curve analysis for NSE (normal 3.7-8.9 ng/mL) and CgA (normal 0-95 ng/mL) as independent diagnostic tests, the following cut-offs were identified: NSE 30.1 (Sn: 37%, Sp: 94%, PPV: 34%, NPV: 82%), CgA 170 (Sn: 63%, Sp: 59%, PPV: 23%, NPV: 83%). Conclusions: Our study confirms the potential utility of serum NSE and CgA in excluding a morphological dx of NEPC when below certain thresholds. However, our findings cannot support deferring a met bx in such cases. Larger studies are needed to evaluate for a more robust predictive ability of serum NE markers. [Table: see text]

Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report

BackgroundAnal canal cancer occasionally accompanies extramammary Paget disease. Although most of them are squamous cell carcinoma, anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease has never been reported.Case presentationHere, we report a 76-year-old man presented with pruritus in the perianal area. Investigation revealed a fist-sized perianal erythema, diffuse liver tumors, and right inguinal lymph node swelling. Pathological examination of biopsies from the erythema suggested secondary extramammary Paget disease with positive cytokeratin-7 and -20 expressions and negative GCDFP-15 expression. The anal canal tumor was confirmed by digital examination and endoscopy. Biopsies from the anal canal tumor, swollen lymph node, and Paget lesion all showed poorly differentiated adenocarcinoma with neuroendocrine features expressing synaptophysin and chromogranin A. Serum CEA and NSE levels were high, 809.4 ng/ml and 85.8 ng/ml, respectively. After chemotherapy with modified FOLFOX6 for 2 months, the Paget lesion disappeared, and the primary anal canal tumor and liver metastases shrunk remarkably. Serum CEA and NSE levels decreased promptly to within normal ranges.ConclusionsThis is a clinically significant case, as it reveals novel pathological features about anal canal cancer with secondary Paget disease and successfully treated with modified FOLFOX6. Careful pathological investigation and appropriate treatment choice are needed for this rare cancer.

Serum Biomarkers and Clinical Outcomes in Traumatic Spinal Cord Injury: Prospective Cohort Study

A plethora of reactive cellular responses emerge immediately after a traumatic spinal cord injury (SCI) and may influence the patient's outcomes. We investigated whether serum concentrations of neuron-specific enolase, interleukin-6, glial-derived neurotrophic factor, and neurotrophic growth factor reflect the acute-phase responses to different etiologies of SCI and may serve as predictive biomarkers of neurologic and functional outcomes. Fifty-two patients were admitted to the intensive care unit after SCI due to traffic accidents, falls, and firearm wounds and had blood samples collected within 48 hours and 7 days after SCI. Thirty-six healthy subjects with no history of SCI were included as controls. Neurologic and functional status was evaluated on the basis of American Spinal Injury Association and Functional Independence Measure scores over a period of 48 hours and 6 months after SCI. Serum NSE increased significantly 48 hours and 7 days after SCI compared with controls, while interleukin-6 increased only at 48 hours. In contrast, the neurotrophic growth factor level significantly decreased 48 hours and 7 days after SCI. Serum glial-derived neurotrophic factor level did not differ from control at any time point. Also, there was no significant difference in biomarker concentrations between the etiologies of SCI or the level of spinal injury. There were no correlations between biomarker levels at 48 hours with neurologic or functional outcomes 7 days and 6 months after SCI. Our results suggest expansive axonal damage coupled with an acute proinflammatory response after SCI. However, in our study biomarker concentration did not correlate with short- or long-term prognosis, such as survival rate or sensory and motor function.

Abstract 253: Increased Blood Brain Barrier Permeability After Successful Resuscitation in a Rat Model of Cardiac Arrest

Introduction: We have previously demonstrated that administration of PEG-20k during cardiopulmonary resuscitation (CPR) improves post-resuscitation neurologic function and survival. Since PEG-20k does not cross the blood brain barrier (BBB) during normal circulation due to its size, the mechanism of improved neurologic function remains unclear. The potential mechanism may be related to an increased permeability of the BBB after cardiac arrest and CPR which allows large molecules like PEG-20k to cross. Hypothesis: The BBB is damaged with increased permeability after successful resuscitation from cardiac arrest. Methods: Ten rats were randomized into two groups, 1) CPR+ Evan’s Blue (EB, molecular weight 68kDa) group; 2) NO CPR+EB group. Ventricular fibrillation was induced and untreated for 8 min for all CPR groups. S-100β, NSE and EB concentrations were analyzed for blood brain barrier (BBB) permeability damage. Results: All animals were resuscitated successfully. Brain permeability was increased in the CPR+EB group after 6h of CPR (p&lt;0.01) (Fig 1). Serum S-100β and NSE levels were significantly higher in the CPR group compared to NO CPR+EB group (p &lt; 0.01) (Fig 1). Conclusions: The function of BBB is impaired after successful resuscitation from cardiac arrest with increased permeability.

Relationship between body temperature, neuron-specific enolase, and clinical course in patients after out-of-hospital cardiac arrest

According to ILCOR (International Liaison Committee on Resuscitation) recommendations (released in 2003), use of therapeutic hypothermia is recommended for unconscious adult patients who have survived acardiac arrest regardless of the initial monitored cardiac rhythm. Thereby, the treatment goal is to achieve and maintain abody temperature of 32-34 °C for aperiod of 12-24 h. According to the October 2015 recommendations of the European Resuscitation Council (ERC), targeted temperature management (TTM) remains part of treatment, but, as an option, it is advised that the targeted body temperature be 36 °C rather than 32-34 °C. For anon-randomized retrospective observational study, atotal of 149 patients were treated with cardiopulmonary resuscitation (CPR) between May 1999 and September 2009. For the first 4days after CPR, data associated with demography, resuscitation, therapy (temperature course, neuron-specific enolase [NSE]) and clinical-neurological development (Glasgow Outcome Scale [GOS]) were collected. In the study, patients receiving mild hyperthermia were compared with those who did not receive hypothermia. Of the 149 patients included, 90were treated with mild hypothermia (as decided by the attending physician), while 59 received no hypothermia therapy. Assessment reveals that mild hypothermia positively influences clinical-neurological progression, but not survival. On day three and four, patients with an unfavorable neurological progression exhibited significantly increased serum levels of NSE (day4: 108.7 ± 137.3 ng/ml versus 25.5 ± 15.4 ng/ml). Patients receiving hypothermia showed lower average NSE levels compared with persons not receiving hypothermia. Furthermore, during the first 4days, their NSE values tended to increase slower (NSE value at day4: 55.9 ± 64.9 ng/ml versus 129.9 ± 174.9 ng/ml). The best cut-off-value for an unfavorable neurological result was 74.2 ng/ml at day four (specificity 100%, sensitivity 48.6%). For the group of patients who received hypothermia, the best cut-off-value was 74.2 ng/ml at day four (specificity 100%, sensitivity 40.9%), and, for the comparison group, best cut-off-value was 25.5 ng/ml at day three (specificity 100%, sensitivity 88.2%). After out-of-hospital resuscitation, there is a trend for improved clinical-neurological progression with mild hypothermia but it does not influence the prognostic significance of serum NSE. After assessment of available data, it is not possible to recommend uniform cut-off values for patients who received mild therapeutic hypothermia and for those who did not receive hypothermia treatment.