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Background: Recent advancements in animal studies have demonstrated the potential of normobaric hyperoxia (NBO) as a promising intervention for preserving the integrity of the blood-brain barrier (BBB). However, there is still limited understanding of the effects of NBO on BBB function in patients with clinical stroke. Therefore, the objective of this study was to investigate the efficacy of NBO therapy in attenuating BBB damage and reducing brain injury in individuals undergoing endovascular treatment (EVT) for acute stroke., Methods and Results: This study enrolled patients from the OPENS-1 (Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke) study, with 43 patients receiving NBO combined with EVT and 43 patients receiving EVT alone. The main outcome measures included serum levels of occludin, MMP-9 (matrix metalloproteinase-9), NSE (neuron-specific enolase), and S100b at 24 hours and 7 days, as well as the intracranial extravasation rate at 24 hours. Serum markers were assessed using ELISA, and intracranial contrast extravasation was visualized using dual-energy computed tomography scan. We analyzed a total of 86 patients and found that the 24-hour serum markers levels of BBB damage and brain injury were significantly lower in the group receiving NBO therapy combined with EVT compared with the group receiving EVT alone. Similarly, at 7 days, the levels of occludin, MMP-9, and NSE were lower in the NBO+EVT group. We also found that the 24-hour serum levels of occludin and MMP-9 were correlated with intracranial contrast extravasation. Additionally, the incidence of intracranial contrast extravasation was lower in the NBO+EVT group compared with the EVT group (35.9% versus 60.5%, P =0.031)., Conclusions: This study offers valuable insights into the positive impact of NBO on maintaining BBB integrity and reducing brain injury in patients with acute stroke undergoing EVT.

The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1 + CD63 + extracellular vesicle detection was reduced after tumor resection while both CD99 + CD63 + and ENO-1 + CD63 + extracellular vesicles were detected in serum from Ewing sarcoma-bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1 + CD81 + extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1 + CD81 + extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotomized as good neurological outcome (CPC 1-2: full recovery or moderate disability) and poor neurological outcome (CPC 3-5: severe disability, vegetative state, or death). Of the 191 adult patients with CA, 42 (22%) had good neurological outcomes, and 149 (78%) had poor neurological outcomes. NSE at 1,3,5,7 and ICU discharge days showed excellent predictive accuracy for neurological outcomes (area under the curve [AUC]: 0.666, 0.716, 0.870, 0.739, and 0.901, respectively). However, S100β exhibited general predictive power (AUC: 0.666, 0.573, 0.607, 0.594, 0.727). Finally, the early warning model, which combined day 1 NSE, day 1 S100β, cardiac arrest time, SOFA scores, APACHE II scores, and age, was used to screen CA patients with poor neurological prognosis at early stages and had an AUC of 0.792. Serum concentrations of NSE and S100β were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100β combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA., (© 2024. The Author(s).)

Delayed neuropsychiatric sequelae (DNS) significantly impact the quality of life in patients following acute carbon monoxide poisoning (COP). This systematic review and meta-analysis aimed to assess the relationship between serum neuron-specific enolase (NSE) levels at admission and the risk of DNS in adults after acute COP. Relevant observational studies with longitudinal follow-up were identified through searches in PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases. The random-effects model was used to aggregate results, accounting for potential heterogeneity. Nine cohort studies, including 1501 patients, were analyzed, with 254 (16.9%) developing DNS during follow-up. The pooled data indicated that elevated serum NSE in the early phase was linked to a higher risk of subsequent DNS (odds ratio per 1 ng/mL increase in NSE: 1.10, 95% confidence interval: 1.06 to 1.15, P < 0.001). Moderate heterogeneity (I2 = 46%) among the studies was entirely attributed to one study with the longest follow-up duration (22.3 months; I2 = 0% after excluding this study). Subgroup analyses based on country, study design, sample size, age, sex, admission carboxyhemoglobin levels, DNS incidence, follow-up duration, and quality score yielded consistent results (P for subgroup differences all > 0.05). In summary, high serum NSE levels in the early phase of acute COP are associated with an increased risk of developing DNS during follow-up.

Background: Diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) is a growing issue, with controversial data in the terms of prevalence and evaluation timelines. Currently, there are no clear standards for its early detection. Therefore, our aim was to assess the contribution of the Michigan neuropathy screening instrument (MNSI), lipid profile, serum neuron specific enolase (NSE), and serum heat shock protein 27 (HSP 27) to the prediction of DPN in children and adolescents with T1DM., Methods: In this case-control study, fifty children diagnosed with T1DM for at least five years were enrolled and evaluated through complete neurological examination, MNSI, and nerve conduction study (NCS). Additionally, HbA1c, lipid profile, serum NSE, and serum HSP 27 levels were measured for patients and controls., Results: The prevalence of DPN in our study was 24% by NCS, and electrophysiological changes showed a statistically significant lower conduction velocity for the posterior tibial and sural nerves, as well as a prolonged latency period for the common peroneal and sural nerves in neuropathic patients. In these patients, older age, earlier age of diabetes onset, longer disease duration, higher total cholesterol, triglycerides, low density lipoprotein cholesterol, HbA1c, serum NSE, and HSP27 levels were observed. The MNSI examination score ≥ 1.5 cutoff point had an area under the curve (AUC) of 0.955, with 75% sensitivity and 94.74% specificity, according to receiver operating characteristic curve analysis. However, the questionnaire's cutoff point of ≥ 5 had an AUC of 0.720, 75% sensitivity, and 63% specificity, with improved overall instrument performance when combining both scores. Regarding blood biomarkers, serum NSE had greater sensitivity and specificity in discriminating neuropathic patients than HSP27 (92% and 74% versus 75% and 71%, respectively). Regression analysis revealed a substantial dependency for MNSI and serum NSE in predicting DPN in patients., Conclusions: Despite limited research in pediatrics, MNSI and serum NSE are promising predictive tools for DPN in children and adolescents with T1DM, even when they are asymptomatic. Poor glycemic control and lipid profile changes may play a critical role in the development of DPN in these patients, despite conflicting results in various studies., (© 2024. The Author(s).)

Background: Though several nomograms have been established to predict the survival probability of patients with small-cell lung cancer (SCLC), none involved enough variables. This study aimed to construct a novel prognostic nomogram and compare its performance with other models., Methods: Seven hundred twenty-two patients were pathologically diagnosed with SCLC in Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University from January 2016 to December 2018. We input Forty-one factors by reviewing the medical records. The nomogram was constructed based on the variables identified by univariate and multivariate analyses in the training set and validated in the validation set. Then we compared the performance of the models in terms of discrimination, calibration, and clinical net benefit., Results: There were eight variables involved in the nomogram: gender, monocyte (MON), neuron-specific enolase (NSE), cytokeratin 19 fragments (Cyfra211), M stage, radiotherapy (RT), chemotherapy cycles (CT cycles), and prophylactic cranial irradiation (PCI). The calibration curve showed a good correlation between the nomogram prediction and actual observation for overall survival (OS). The area under the curve (AUC) of the nomogram was higher, and the Integrated Brier score (IBS) was lower than other models, indicating a more accurate prediction. Decision curve analysis (DCA) showed a significant improvement in the clinical net benefit compared to the other models., Conclusions: We constructed a novel nomogram to predict OS for patients with SCLC using more comprehensive and objective variables. It performed better than existing models and would assist clinicians in individually estimating risk and making a therapeutic regimen., (© 2024. The Author(s).)

Value of choromogranin A and neuron-specific enolase intracystic (EUS-FNB) in the preoperatory diagnosis of cystic pancreatic neuroendocrine tumors.

Background: Aorto-ostial (AO) coronary interventions may be associated with multiple problems, including the potential embolization of atherothrombotic debris into the aorta and systemic circulation. Such embolization could theoretically lead to stroke or silent brain injury (SBI). In this study, we aimed to investigate whether there is an increased risk of SBI in patients undergoing AO stent implantation., Methods: Fifty-five consecutive patients undergoing AO stenting and 55 consecutive patients undergoing non-AO stenting were included. Venous blood samples were obtained before and 12 h after the procedure to measure neuron-specific enolase (NSE), which is a sensitive marker of brain injury. Newly developed NSE elevation after the procedure in an asymptomatic patient was defined as SBI., Results: SBI was detected in 24 (43.6%) patients in the AO stenting group and 17 (30.9%) patients in the non-AO stenting group ( p = .167). Although the SBI rates were statistically comparable between the groups, the presence of significant (≥50%) AO stenosis was found to be an independent predictor of SBI in multivariate logistic regression analysis [odds ratio (OR) 2.856; 95% confidence interval (CI) 1.057-7.716; p = .038]. A longer procedure time was another independent predictor for the development of SBI (OR 1.037; 95% CI 1.005-1.069; p = .023)., Conclusion: This study suggests that AO stenting may be associated with an increased risk of SBI if the lesion in the ostium is significant.

Background and Objectives : Most patients who are successfully resuscitated from cardiac arrest remain comatose, and only half regain consciousness 72 h after the arrest. Neuroprognostication methods can be complex and even inconclusive. As mitochondrial components have been identified as markers of post-cardiac-arrest injury and associated with survival, we aimed to investigate cytochrome c and mtDNA in comatose patients after cardiac arrest to compare neurological outcomes and to evaluate the markers' neuroprognostic value. Materials and Methods : This prospective observational study included 86 comatose post-cardiac-arrest patients and 10 healthy controls. Cytochrome c and mtDNA were determined at admission. Neuron-specific enolase (NSE) was measured after 72 h. Additional neuroprognostication methods were performed when patients remained unconscious. Cerebral performance category (CPC) was determined. Results : Cytochrome c was elevated in patients compared to healthy controls (2.029 [0.85-4.97] ng/mL vs. 0 [0.0-0.16], p < 0.001) but not mtDNA (95,228 [52,566-194,060] vs. 41,466 [28,199-104,708] copies/μL, p = 0.074). Compared to patients with CPC 1-2, patients with CPC 3-5 had higher cytochrome c (1.735 [0.717-3.40] vs. 4.109 [1.149-8.457] ng/mL, p = 0.011), with no differences in mtDNA (87,855 [47,598-172,464] vs. 126,452 [69,447-260,334] copies/μL, p = 0.208). Patients with CPC 1-2 and CPC 3-5 differed in all neuroprognostication methods. In patients with good vs. poor neurological outcome, ROC AUC was 0.664 ( p = 0.011) for cytochrome c, 0.582 ( p = 0.208) for mtDNA, and 0.860 ( p < 0.001) for NSE. The correlation between NSE and cytochrome c was moderate, with a coefficient of 0.576 ( p < 0.001). Conclusions : Cytochrome c was higher in comatose patients after cardiac arrest compared to healthy controls and higher in post-cardiac-arrest patients with poor neurological outcomes. Although cytochrome c correlated with NSE, its neuroprognostic value was poor. We found no differences in mtDNA.

Background: The incidence of post-stroke depression (PSD) may be higher in patients with cancer-associated ischemic stroke (CAIS). The pathogenesis of PSD is mainly related to the emotional injury of stroke and the inability of neurons to effectively repair. This study aims to explore the clinical significance of serum neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) expression levels in CAIS patients., Methods: Clinical data of 106 patients with CAIS admitted to Jinhua Guangfu Oncology Hospital from January 2012 to December 2022 were retrospectively analyzed. Serum levels of NSE, BDNF and CNTF were measured in all patients after admission. Depression screening was performed by Hamilton Depression Scale-17 (HAMD-17) three months after intravenous thrombolysis. Patients with HAMD-17 score >7 were included in the PSD group (n = 44), and patients with HAMD-17 score ≤7 were included in the non-PSD group (n = 62). The general data and serum levels of NSE, BDNF and CNTF were compared between the two groups. According to HAMD-17 scores, patients in PSD group were further divided into mild depression group (8-16 points), moderate depression group (17-23 points) and severe depression group (≥24 points), and the serum levels of NSE, BDNF and CNTF were compared among the three groups. Pearson's correlation test was used to analyze the correlation between HAMD-17 scores and serum NSE, BDNF and CNTF levels in PSD patients. Logistic regression model was used to determine the influencing factors of PSD in CAIS patients. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive efficacy of serum NSE, BDNF, CNTF and their combination on PSD., Results: Among 106 CAIS patients, the incidence of PSD was 41.51% (44 cases), including 19 patients with mild PSD (43.18%), 14 patients with moderate PSD (31.82%), and 11 patients with severe PSD (25.00%). There were statistically significant differences in negative life events and complications after thrombolytic therapy between PSD and non-PSD patients (p < 0.05). The serum NSE level in PSD group was significantly higher than that in non-PSD group, and the serum BDNF and CNTF levels were notably lower than those in non-PSD group (all p < 0.001). The serum levels of NSE, BDNF and CNTF in patients with different severity of PSD were statistically significant (all p < 0.001). HAMD-17 scores in PSD patients were positively correlated with serum NSE levels (r = 0.676, p < 0.001) and negatively correlated with serum BDNF and CNTF levels (r = -0.661, p < 0.001; r = -0.401, p = 0.007, respectively). By binary logistic regression analysis, the levels of serum NSE, BDNF and CNTF were independent influencing factors for PSD in CAIS patients, among which NSE was a risk factor (odds ratio (OR) >1, p < 0.05), BDNF and CNTF were protective factors (OR <1, p < 0.05)., Conclusion: This study reveals for the first time that the levels of serum NSE, BDNF and CNTF are closely related to the occurrence and development of PSD in CAIS patients. In clinical CAIS patients with abnormal changes in the above indicators, in addition to anti-tumor treatment and improvement of neurological deficit symptoms, attention should also be paid to the symptoms of psychological disorders.

We read with great interest the review article on pathophysiology and treatment based on different out-of-hospital cardiac arrest (OHCA) patients. We wish to present our comments on the threshold values for neuron-specific enolase (NSE) based on the initial rhythm and the misquoting of a few references in that article.

Background and Objectives : Silent cerebral ischemia (SCI) is defined as a condition that can be detected by biochemical markers or cranial imaging methods but does not produce clinical symptom. This study aims both to compare the frequency of SCI in PCIs performed with right transradial access and left transradial access and to evaluate the influencing factors. Materials and Methods : A prospective, single-center study included 197 patients undergoing PCI via transradial access between November 2020 and July 2022. The patients were categorized into right radial and left radial groups. Neuron-specific enolase (NSE) values were measured and recorded before and 18 h after the procedure. A post-procedure NSE level higher than 20 ng/dL was defined as SCI. Results : SCI occurred in 60 of the 197 patients. NSE elevation was observed in 37.4% ( n = 37) of the right radial group and in 23.5% ( n = 23) of the left radial group ( p = 0.032). Patients with SCI had higher rates of smoking ( p = 0.043), presence of subclavian tortuosity ( p = 0.027), and HbA1c ( p = 0.031). In the multivariate logistic regression analysis, the level of EF (ejection fraction) (OR: 0.958 95% CI 0.920-0.998, p = 0.039), right radial preference (OR: 2.104 95% CI 1.102-3.995 p = 0.023), and smoking (OR: 2.088 95% CI 1.105-3.944, p = 0.023) were observed as independent variables of NSE elevation. Conclusions : Our findings suggest that PCI via right radial access poses a greater risk of SCI compared to left radial access. Anatomical considerations and technical challenges associated with right radial procedures and factors such as smoking and low ejection fraction contribute to this elevated risk.

Objective: This study aimed to investigate the serum levels of neuron-specific enolase (NSE) in sepsis-associated encephalopathy (SAE) and perform a meta-analysis to assess the diagnostic and prognostic potential of serum NSE in SAE patients., Methods: We searched English and Chinese databases for studies related to SAE that reported serum NSE levels until November 2023. We extracted information from these studies including the first author and year of publication, the number of samples, the gender and age of patients, the collection time of blood samples in patients, the assay method of serum NSE, the study methods, and the levels of serum NSE with units of ng/mL. The quality assessment of diagnostic accuracy studies 2 (QUADAS-2) tool was used to evaluate the study quality. A meta-analysis was performed using Review Manager version 5.3, employing either a random effects model or a fixed effects model., Results: A total of 17 studies were included in the final meta-analysis, including 682 SAE patients and 946 NE patients. The meta-analysis demonstrated significantly higher serum NSE levels in SAE patients compared to NE patients (Z = 5.97, P < 0.001, MD = 7.79, 95%CI 5.23-10.34), irrespective of the method used for serum NSE detection (Z = 6.15, P < 0.001, mean difference [MD] = 7.75, 95%CI 5.28-10.22) and the study methods (Z = 5.97, P < 0.001, MD = 7.79, 95%CI 5.23-10.34). Furthermore, sepsis patients with a favorable outcome showed significantly lower levels of serum NSE compared to those with an unfavorable outcome (death or adverse neurological outcomes) (Z = 5.44, P < 0.001, MD = - 5.34, 95%CI - 7.26-3.42)., Conclusion: The Serum level of NSE in SAE patients was significantly higher than that in septic patients without encephalopathy. The higher the serum NSE level in SAE patients, the higher their mortality rate and incidence of adverse neurological outcomes., (© 2024. The Author(s).)

Concussive and subconcussive head impatcs in sports have drawn more attention in recent years. Thus, the cognitive ability of soccer players and its relationship with circulating levels of irisin, brain-derived neurotrophic factor (BDNF), and neuron-specific enolase (NSE) were studied in this study. Fifteen amateur soccer players and 15 sedentary men volunteered to participate in this study. After evaluating the aerobic and anaerobic capacities of the participants, their cognitive performances were measured. Blood samples were obtained at rest, and the ELISA method was used to measure the concentrations of serum NSE, plasma BDNF, and irisin. There were no differences between groups in terms of cognitive abilities or serum NSE levels (P > 0.05). Plasma irisin (P = 0.019) and BDNF (P < 0.001) levels were higher in the soccer players than the sedentary subjects. There was a positive correlation between irisin and NSE (r = 0.461, P = 0.010) and BDNF (r = 0.405, P = 0.007) concentrations. General cognitive performance is maintained in amateur soccer players. This is accompanied by the unchanged NSE. However, elevated irisin and BDNF levels appear to be independent of cognitive performance.

Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 μg/L) and guideline-suggested (NSE < 60 μg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 μg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 μg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 μg/L, and 87.34% and 82.24% of NSE < 60 μg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients' tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Neurospecific Enolase (NSE), a multifunctional protein, is present in various tissues of the body and plays an important role in many disease processes, such as infection, inflammation, tumours, injury, and immunity. In recent years, the application of NSE in respiratory diseases has become increasingly widespread and a research hotspot., Objective: This study aims to explore the relationship between NSE and childhood pneumonia, providing assistance for the diagnosis and assessment of pneumonia., Methods: Using prospective research and case-control methods, We selected 129 children with pneumonia hospitalised in Weifang People's Hospital from September 2020 to April 2022 as the case group. Among them were 67 cases of Mycoplasma pneumoniae pneumonia (MP+), 62 cases of non-Mycoplasma pneumoniae pneumonia (MP -), and 21 cases of severe pneumonia. At the same time, 136 children who underwent outpatient health examinations were selected as the control group. The levels of NSE, ESR, CRP in cases group and NSE in control group were measured separately., Result: The NSE levels in the MP + group were 17.86 (14.29-22.54) ng/mL, while those in the MP- group were 17.89 (14.10-21.66) ng/mL, both of which were higher than the control group's NSE levels of 13.26(12.18,14.44) ng/mL (H = 46.92, P = 0.000). There was no statistically significant difference in NSE levels between the MP + and MP - groups (P > 0.05). The NSE level in the severe pneumonia group was 27.38 (13.95-34.06) ng/mL, higher than that in the mild pneumonia group, which was 17.68 (14.27-21.04) ng/mL, (P = 0.024). The AUC values for diagnosing pneumonia are NSE0.714, CRP0.539, and ESR0.535, with NSE having the highest diagnostic value., Conclusion: Serum NSE can serve as an inflammatory indicator for paediatric pneumonia, which has important clinical guidance significance for the diagnosis, condition evaluation, and prognosis of paediatric pneumonia., (© 2024. The Author(s).)

Background: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method., Methods: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method., Results: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes., Conclusion: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories., (© 2024. The Author(s).)

Since the discovery of the neuron-specific protein by Moore and McGregor in 1965, tens of thousands of studies have investigated the basic and applied significance of neuron-specific enolase (NSE). This promising biomarker, according to many researchers, has not found widespread use in clinical practice, particularly in acute cerebrovascular accidents. Moreover, the several studies refuting the usefulness of serum NSE measurement in critically ill patients leads us to consider the reasons for such contradictory conclusions. In this article, we have analyzed the main directions in the study of NSE and expressed our perspective on the reasons for the contradictory results and the difficulties in implementing the results of these studies in clinical practice. In our opinion, the method of the enzyme-linked immunosorbent assay (ELISA) used in the majority of the studies is inappropriate for the evaluation of NSE as a marker of central nervous system damage, because it does not allow for the differentiation of heterodimers of enolases and the assessment of the enzymatic activity of this group of enzymatic proteins. Therefore, the methodological approach for the evaluation of NSE (γγ-enolase) as a biomarker needs to be elaborated and improved. Furthermore, the specificity of the applied research methods and the appropriateness of the continued use of the term "neuron-specific enolase" must be addressed.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case ( n = 29) with a neonate who had a normal head ultrasound scan ( n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life ( p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates ( p = 0.003), and (c) between control and the five ( n = 5) neonates that died from the case group ( p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Introduction: Sepsis-associated brain dysfunction is a common organ dysfunction in sepsis. The main goal of this study was to verify whether the combined assessment of central nervous system injury markers (i.e. S100B, NSE, GFAP) and disease severity as per the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) classification systems, would increase the accuracy of death prediction in septic shock., Material and Methods: Markers of neuronal damage were determined in 55 patients diagnosed with septic shock with no previous neurological disease. Clinical data was collected and the scores on the APACHE II, SAPS II and SOFA prognostic scales were calculated. Death before discharge from the Intensive Care Unit (ICU) was established as the endpoint., Results: Nineteen patients (35%) died before ICU discharge. Patients who died had significantly higher S100B and NSE values, and APACHE II, SAPS II and SOFA scores (P< 0.05 for all). At the time of septic shock diagnosis, NSE levels more accurately predicted the risk of death before ICU discharge than S100B. However, NSE had no better predictive value for short-term mortality than APACHE II, SAPS II and SOFA. Adding C-reactive protein (CRP) and S100B concentrations to the APACHE II score created a predictive model with 95% mortality accuracy (AUC = 0.95; 95%CI 0.85-0.99; P = 0.03)., Conclusions: The assessment of acute neuronal injury plays an important role in prognostication in patients with septic shock. The concentration of S100B protein in combination with APACHE II score and concentration of CRP more accurately predicts mortality than the APACHE II alone.

Aim: To observe changes in the serum levels of visinin-like protein-1 (VILIP-1), caveolin-1 (Cav-1) and neuron-specific enolase (NSE) after glioma resection., Material and Methods: Consecutive 14 glioma patients with different histologic grade and 14 age and gender-matched healthy subjects were included in this pilot study. From the patients serum samples were taken in preoperative and on day 2 and 10 of postoperative periods. Healthy subjects provided serum sample once. The serum changes of three proteins were evaluated by ELISA. The results were compared between preoperative and postoperative periods and between patients and controls., Results: Preoperative serum levels of VILIP-1 (p=0.008) and Cav-1 (p=0.012) were significantly higher in the patients. Mean serum levels of VILIP-1 (p=0.002) and Cav-1 (p=0.013) again were significantly higher than those of the controls. NSE did not show significant changes compared to controls in none of the periods. There was a steady decline regarding all three molecules from preoperative to postoperative day 10. However, statistical comparisons did not reveal any significant difference with respect the decline in any molecule. Significant positive correlation was detected between preoperative serum levels of VILIP-1 and Cav-1 (p=0.00001) in the patients and the controls (p=0.0000)., Conclusion: This pilot study suggested that Cav-1 and particularly VILIP-1 may be used as a valuable serum biomarker for follow-up and for early detection of recurrence in high-grade gliomas. Future studies including larger cohort of patients with homogeneous group of glioma is required.

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.)

Objective: To investigate the clinical value of serum neuron-specific enolase (NSE) combined with serum S100B protein in the diagnosis of systemic lupus erythematosus (SLE)., Methods: Sixty patients with SLE treated in our hospital from January 2019 to April 2021 were enrolled as the study group. According to the degree of activity, the study group was assigned into three groups: mild activity group ( n  = 20), moderate activity group ( n  = 20), and severe activity group ( n  = 20). A total of 60 healthy people who underwent physical examination in our hospital in the same period were enrolled as the control group. The NSE and serum S100B protein were detected in the two groups, and the correlation between serum nerve-specific enolase and serum S100B protein and the clinical value in the diagnosis of SLE were analyzed., Results: First of all, we compared the general data of the two groups. There was no significant difference in sex, age, marital status, and education level, and no significant difference was exhibited ( p  > 0.05). There was no significant difference in sex, age, marital status, and education level among mild activity group, moderate activity group, and severe activity group, and no significant difference in data was exhibited ( p  > 0.05). Secondly, we compared the levels of serum S100B protein and NSE. The levels of serum S100B protein and NSE in the study group were higher compared to the control group ( p  < 0.05). The levels of serum S100B protein and NSE in patients with different activity levels of SLE were compared. The levels of serum S100B protein and NSE in mild activity group < moderate activity group < severe activity group were significantly different ( p  < 0.05). Correlation analysis between serum S100B, NSE levels, and SLE activity indicated that serum S100B and NSE levels were positively correlated with SLE activity. With the increase of SLE activity, serum S100B and NSE levels gradually increased, and the data difference was statistically significant ( r  = 0.855, 0.844, p  < 0.05). Finally, we established the logistic prediction model, take the probability of generating prediction as the analysis index, and draw the ROC curve to evaluate the diagnostic value of different combinations to SLE. The highest AUC and sensitivity of the two indexes in the diagnosis of SLE were 0.773 and 0.836, respectively. The levels of serum S100B protein and NSE have a certain value in the diagnosis of SLE, while the combined diagnosis is of higher value, sensitivity, and specificity in the diagnosis of SLE., Conclusion: Serum S100B protein and NSE are very sensitive indexes to judge the damage of central nervous system. However, due to the small number of cases in this study, there were as many as 19 kinds of NPSLE classification, so the relationship between serum S100B protein, NSE levels, and various NPSLE and their exact application value in diagnosing the disease and judging the prognosis needs to be confirmed by expanding the number of cases., Competing Interests: The authors declare that they have no conflicts of interests regarding the publication of this paper., (Copyright © 2022 Jing Chen et al.)

We compared the cut-off and prognostic value of serum neuron-specific enolase (NSE) between groups with and without severe blood-brain barrier (BBB) disruption to reveal that a cause of various serum NSE cut-off value for neurological prognosis is severe BBB disruption in out-of-hospital cardiac arrest (OHCA) patients underwent target temperature management (TTM). This was a prospective, single-centre study conducted from January 2019 to June 2021. Severe BBB disruption was indicated using cerebrospinal fluid-serum albumin quotient values > 0.02. The area under the receiver operating characteristic curve of serum NSE obtained on day 3 of hospitalisation to predict poor outcomes was used. In patients with poor neurologic outcomes, serum NSE in those with severe BBB disruption was higher than in those without (P = 0.006). A serum NSE cut-off value of 40.4 μg/L for poor outcomes in patients without severe BBB disruption had a sensitivity of 41.7% and a specificity of 96.0%, whereas a cut-off value of 34.6 μg/L in those with severe BBB disruption had a sensitivity of 86.4% and a specificity of 100.0%. We demonstrated that the cut-off and prognostic value of serum NSE were heterogeneous, depending on severe BBB disruption in OHCA patients treated with TTM., (© 2022. The Author(s).)

Objective: To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE)., Methods: The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment., Results: After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups ( P < 0.05). The levels of neuron-specific enolase (NSE), S-100 β protein, and plasma neuropeptide Y (NPY) in the combination group were lower than those in the other two groups, and the recovery time of consciousness, muscle tension, and reflex was shorter ( P < 0.05). The combination group showed higher total effective rate and lower incidence of complications as compared with the other two groups ( P < 0.05)., Conclusion: Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Jingjing Ge et al.)

Neurological examination in the acute phase after spinal cord injury (SCI) is often impossible and severely confounded by pharmacological sedation or concomitant injuries. Therefore, diagnostic biomarkers that objectively characterize severity or the presence of SCI are urgently needed to facilitate clinical decision-making. This study aimed to determine if serum markers of neural origin are related to: 1) presence and severity of SCI, and 2) magnetic resonance imaging (MRI) parameters in the very acute post-injury phase. We performed a secondary analysis of serological parameters, as well as MRI findings in patients with acute SCI ( n  = 38). Blood samples were collected between Days 1-4 post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and neurofilament light protein (NfL) were determined. A group of 41 age- and sex-matched healthy individuals served as control group. In the group of individuals with SCI, pre-operative sagittal and axial T2-weighted and sagittal T1-weighted MRI scans were available for 21 patients. Serum markers of neural origin are different among individuals who sustained traumatic SCI depending on injury severity, and the extent of the lesion according to MRI in the acute injury phase. Unbiased Recursive Partitioning regression with Conditional Inference Trees (URP-CTREE) produced preliminary cut-off values for NfL (75.217 pg/mL) and GFAP (73.121 pg/mL), allowing a differentiation between individuals with SCI and healthy controls within the first 4 days after SCI. Serum proteins NfL and GFAP qualify as diagnostic biomarkers for the presence and severity of SCI in the acute post-injury phase, where the reliability of clinical exams is limited.

Background: Delirium is the most common central nervous system complication after surgery. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage within the central cervous system and is associated with the severity of postoperative delirium. Neuron-specific enolase and S100 calcium-binding protein β have been identified as possible serum biomarkers of postoperative delirium. This study examined the association of the levels of these markers with incidence of postoperative delirium and detection of phosphorylated neurofilament heavy subunit., Methods: This study represents a post hoc analysis of 117 patients who participated in a prospective observational study of postoperative delirium in patients undergoing cancer surgery. Patients were clinically assessed for development of postoperative delirium within the first five days of surgery. Serum levels of phosphorylated neurofilament heavy subunit, neuron-specific enolase, and S100 calcium-binding protein β levels were measured on postoperative day 3., Results: Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Neuron-specific enolase level (P < 0.0001) and the proportion of patients positive for phosphorylated neurofilament heavy subunit (P < 0.0001) were significantly higher in the group of patients with postoperative delirium. Neuron-specific enolase level discriminated between patients with and without clinically diagnosed postoperative delirium with significantly high accuracy (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.79-0.95; P < 0.0001). Neuron-specific enolase level was associated with incidence of postoperative delirium independently of age (adjusted odds ratio, 8.291; 95% Cl, 3.506-33.286; P < 0.0001). The AUC for the serum neuron-specific enolase level in detecting phosphorylated neurofilament heavy subunit was significant (AUC, 0.78; 95% CI, 0.66-0.90; P < 0.0001)., Conclusion: Elevated serum neuron-specific enolase was associated with postoperative delirium independent of age as well as detection of phosphorylated neurofilament heavy subunit in serum. Serum neuron-specific enolase and phosphorylated neurofilament heavy subunit might be useful as biomarkers of postoperative delirium., Trial Registration: University Medical Information Network (UMIN) trial ID: UMIN000010329; https://clinicaltrials.gov/., Competing Interests: The Department of Pain and Palliative Medical Sciences, where M. Hasegawa-Moriyama works, is sponsored by Shionogi Co., Ltd. (Osaka, Japan) and Nippon Zoki Pharmaceutical Co., Ltd. (Osaka, Japan). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Abstract: Accurate neurological prognostication is of the utmost importance to avoid futile treatments in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). This study aimed to investigate the prognostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) by comparing with neuron-specific enolase (NSE), which is currently recommended by international guidelines in patients treated with TTM after OHCA.The study included 85 comatose adult patients with OHCA who underwent TTM between May 2018 and December 2020. Serum NGAL and NSE were measured at 24-hour intervals until 72 hours after return of spontaneous circulation (ROSC). The primary outcome was their prognostic performance for poor neurological outcome at 3 months after OHCA.Forty-nine patients (57.6%) had a poor neurological outcome; NGAL levels at all time points measured were significantly higher in these patients than in those with a good outcome (P < .01). NGAL showed lower maximal sensitivity (95% confidence interval [CI]) under a false-positive rate of 0% for the primary outcome compared with NSE (18.2% [95% CI 8.2-32.7] vs 66.7% [95% CI 50.5-80.4]). The combination of NGAL with NSE at 48 h showed the highest sensitivity (69.1% [95% CI 52.9-82.4]) and had the highest area under the curve (0.91 [95% CI 0.81-0.96]) for a poor outcome. The prognostic performance of NGAL alone was inadequate at all time points. However, NGAL combined with NSE at 24 and 28 hours after ROSC showed improved sensitivity compared to NGAL alone.NGAL should be considered a supplementary biomarker in combination with NSE for prognostication in patients with OHCA treated with TTM., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare tumor. MiNEN of the gallbladder (GB) with pancreaticobiliary maljunction (PMJ) is extremely rare. The origin of MiNEN of the GB remains unknown; the biliary tract normally lacks neuroendocrine cells. MiNEN of the GB has a poor prognosis; because of its rarity, no treatment or management guidelines have been established yet., Patient Concerns: A 47-year-old male presenting with right hypochondrial pain and malaise for 3 months was referred to our hospital for further management., Diagnosis: The neuron-specific enolase level was increased. Contrast-enhanced computed tomography revealed a mass of 70 mm in size with unclear boundaries in the liver. The GB was surrounded by this mass, narrowing the lumen of the GB. Many swollen lymph nodes were observed in the hepatoduodenal ligament. Endoscopic retrograde cholangiopancreatography revealed a PMJ with a non-dilated biliary duct. A percutaneous biopsy was performed on the liver mass, and the pathological findings were neuroendocrine carcinoma (NEC) (small cell type). We diagnosed a NEC of the GB, T3N1M0, stage IIIB (Union for International Cancer Control, 7th edition)., Interventions: Because of advanced lymph node metastasis, we considered this tumor difficult to cure solely by surgical intervention. After initial chemotherapy consisting of cisplatin and irinotecan, a marked reduction in both tumor and lymph node sizes enabled conversion surgery. The pathological diagnosis of the resected tumor was MiNEN consisting of NEC and adenocarcinoma. The primary lesion was the adenocarcinoma occupying the luminal side of the GB. As a postsurgical treatment, the patient received additional irradiation therapy to the common hepatic duct and liver stump because of positive surgical margins., Outcomes: At 13 months postoperatively, computed tomography findings revealed the appearance of a hypervascular liver tumor, and laboratory data showed increased serum neuron-specific enolase levels. Chemotherapy was unsuccessful, leading to the death of the patient 36 months from the date of diagnosis., Lessons: There are several reports on the development of MiNEN of the GB. In our case, a PMJ-related adenocarcinoma of the GB transdifferentiated into NEC. Further accumulation of cases is necessary to establish a treatment strategy for MiNEN of the GB., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Renal cell carcinoma is prone to early metastasis. In general, intraocular metastasis (IOM) is not common. In the present study, we studied the relationship between different biochemical indicators and the occurrence of IOM in renal cancer patients, and identified the potential risk factors., Methods: A retrospective analysis of the clinical data of 214 patients with renal cell carcinoma from October 2001 to August 2016 was carried out. The difference and correlation of various indicators between the two groups with or without IOM was analyzed, and binary logistic regression analysis was used to explore the risk factors of IOM in renal cancer patients. The diagnostic value of each independent related factor was calculated according to the receiver operating curve (ROC)., Results: The level of neuron-specific enolase (NSE) in renal cell carcinoma patients with IOM was significantly higher than that in patients without IOM (P<0.05). There was no significant difference in alkaline phosphatase (ALP), hemoglobin (Hb), serum calcium concentration, α fetoprotein (AFP), carcinoembryonic antigen (CEA), CA-125 etc. between IOM group and non-IOM (NIOM) group (P>0.05). Binary logistic regression analysis showed that NSE was an independent risk factor for IOM in renal cell carcinoma patients (P<0.05). ROC curve shows that the factor has high accuracy in predicting IOM, and the area under the curve (AUC) is 0.774. The cut-off value of NSE was 49.5 U/l, the sensitivity was 72.2% and the specificity was 80.1%., Conclusion: NSE concentration is a risk factor for IOM in patients with renal cell cancer. If the concentration of NSE in the patient's body is ≥49.5 U/l, disease monitoring and eye scans should be strengthened., (© 2021 The Author(s).)

The study is aimed at studying the association between the levels of serum adiponectin (ADPN), high-sensitivity C-reactive protein (hs-CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) and hypertensive cerebrovascular complications. 50 patients with hypertensive cerebrovascular disease treated in Gansu Provincial Hospital from December 2016 to December 2018 were selected as the experimental group, and 50 normal people who underwent physical examination were selected as the control group. The blood pressure, heart rate, and the complications were recorded, and the serum blood lipid indexes were detected. Moreover, the content of serum ADPN, hs-CRP, and sICAM-1; the neurological indexes; brain-derived neurotrophic factor (BNDF); and neurone-specific enolase (NSE) were also determined using ELISA. The content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCR) in the experimental group was significantly higher than that in control group ( p < 0.05); the incidence of cerebrovascular complications, systolic blood pressure, diastolic blood pressure, and heart rate increased ( p < 0.05); the content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hs-CRP, and sICAM-1 obviously rose ( p < 0.05); and the content of ADPN and HDL obviously declined ( p < 0.05). Besides, the experimental group had evidently lower systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd), and mean blood flow velocity (Vm) and evidently higher pulsatility index (PI) ( p < 0.05). The levels of S100 and NSE in the experimental group increased significantly, and the level of BNDF decreased significantly ( p < 0.05). In patients with hypertensive cerebrovascular disease, the level of ADPN declines; the levels of hs-CRP and sICAM-1 rise; the incidence rate of cerebrovascular complications is elevated; and there are changes in the blood lipid, cerebrovascular hemodynamic, and neurological indexes, thereby further promoting the occurrence and development of hypertensive cerebrovascular disease., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Haijun Niu et al.)

Abstract: There has been no effective biomarker for small cell lung cancer (SCLC) patients with first-line immune checkpoint inhibitors (ICIs) treatment. The predictive value of neuron-specific enolase (NSE) in this cohort remains unclear.The medical records of 254 consecutive SCLC patients receiving programmed cell death receptor-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors were compiled from January 2015 to October 2020 in Chinese PLA General Hospital. Survival analysis was performed to explore the prognostic role of NSE at baseline and 3 weeks post treatment.One hundred two advanced SCLC patients treated with first-line PD-1/PD-L1 inhibitors were enrolled in this study. Normal baseline NSE levels were correlated with significantly prolonged progression-free survival (PFS, median: 8.7 vs 4.7 months, P = .006) and overall survival (OS, median: 23.8 vs 15.2 months, P = .014) compared with elevated baseline NSE levels, so as for normal NSE levels at 3 weeks with prolonged PFS (median PFS: 8.4 vs 4.5 months, P = .0002) and OS (median OS: 23.3 vs 7.4 months, P < .0001). Intriguingly, elevated NSE levels at 3 weeks were associated with shorter PFS (median PFS: 4.5 vs 5.8 months, P = .04) and OS (median OS: 5.5 vs 14.7 months, P < .0001) compared with normal NSE levels in the elevated baseline NSE subgroup. Most subgroup analyses stratified by clinical characteristics confirmed the prognostic value of baseline NSE level.Elevated NSE levels at baseline and 3 weeks were associated with worse prognosis in advanced SCLC patients receiving first-line ICIs treatment. NSE level might be applied as a useful prognostic tool for SCLC patients with immunotherapy., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Lung cancer is one of the most common malignancies, and there is a trend of increasing incidence in young patients. The preoperative diagnosis of pulmonary nodules is mainly based on the combination of imaging and tumor markers. There is no relevant report on the diagnostic value of tumor markers in young pulmonary nodules. Our study was designed to explore the value of five tumor markers in young patients with pulmonary nodules., Methods: We reviewed the medical records of 390 young patients (age ≤45 years) with pulmonary nodules treated at two separate centers from January 1, 2015, to January 1, 2021. Malignant pulmonary nodules were confirmed in 318 patients, and the other 72 patients were diagnosed with benign pulmonary nodules. The gold standard for diagnosis of pulmonary nodules was surgical biopsy. The conventional serum biomarkers included cytokeratin 19 (CYFRA21-1), pro-gastrin-releasing-peptide (ProGRP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma-associated antigen (SCCA). The diagnostic values of five tumor markers were analyzed by receiver operating characteristic (ROC) curves., Results: There were no significant differences in the expression of five tumor markers between the groups (p > 0.05). Single tumor marker (CYFRA21-1, ProGRP, CEA, NSE, and SCCA) showed a limited value in the diagnosis of malignant pulmonary nodules, with the AUC of 0.506, 0.503 0.532, 0.548, and 0.562, respectively. The AUC of the combined examination was only 0.502~0.596, which did not improve the diagnostic value., Conclusions: Five conventional tumor markers had a limited diagnostic value in young patients with pulmonary nodules., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: Serum neuron-specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test., Methods: The reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots., Results: The high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = -0.069, p = 0.640). The 95% confidence interval of mean difference (from -8.33% to 12.17%) was less than the acceptable bias range (±20%)., Conclusion: The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background/aim: Postnatal corticosteroids are commonly used to treat bronchopulmonary dysplasia (BPD). We aimed to show whether S100 calcium-binding B (S100B), neuron-specific enolase (NSE), Tau protein or microtubule-associated protein tau (MAPT), and glial fibrillary acid protein (GFAP) levels would provide any evidence of early neurological damage in premature infants receiving postnatal low dose dexamethasone therapy for BPD treatment., Materials and Methods: In this cohort study, 136 preterm infants diagnosed with BPD at ≤32 weeks of gestation formed the study group, and 64 preterm infants formed the control group. NSE, S100B, GFAP, and MAPT levels were first measured before the postnatal corticosteroid treatment in both the patient and the control group on the 28th day and, for a second time, after treatment termination in the patient group., Results: There were significant differences between the measured GFAP, MAPT, and NSE values of the BPD and control groups on the 28th day, whereas there was no significant difference between the measured S100B values of the two groups. There were a statistically significant difference between the NSE values measured on the 28th day and after the treatment within the BPD group, whereas no significant difference existed between the GFAP, MAPT, and S100B values., Conclusion: NSE levels, which indicate brain damage in the early period, increased in preterm babies with BPD who had been administered postnatal dexamethasone., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background: Increased serum neuron-specific enolase (NSE) level was found in a substantial proportion (30-69%) of patients with non-small-cell lung cancer (NSCLC), but little was known about the clinical properties of NSE in NSCLC., Objective: We aimed to assess the level of serum NSE to predict prognosis and treatment response in patients with advanced or metastatic non-neuroendocrine NSCLC., Methods: We retrospectively analyzed 363 patients with advanced and metastatic NSCLC between January 2011 and October 2016. The serum NSE level was measured before initiation of treatment., Results: Patients with high NSE level (≥26.1 ng/ml) showed significantly shorter progression-free survival (PFS) (5.69 vs 8.09 months; P=0.02) and significantly shorter overall survival (OS) than patients with low NSE level (11.41 vs 24.31 months; P=0.01). NSE level was an independent prognostic factor for short PFS (univariate analysis, hazard ratio [HR] = 2.40 (1.71-3.38), P<0.001; multivariate analysis, [HR] = 1.81 (1.28-2.56), P=0.001) and OS (univariate analysis, [HR] = 2.40 (1.71-3.37), P<0.001; multivariate analysis, [HR] = 1.76 (1.24-2.50), P=0.002)., Conclusion: The survival of NSCLC patients with high serum NSE level was shorter than that of NSCLC patients with low serum NSE levels. Serum NSE level was a predictor of treatment response and an independent prognostic factor., (© 2021 The Author(s).)

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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.)

Mild traumatic brain injury (mTBI) is the most prevalent neurological insult and leads to long-lasting cognitive impairment. Neuroimaging studies have discovered abnormalities in brain network connectivity following mTBI as the underlying neural basis of cognitive deficits. However, the pathophysiologic mechanisms involved in imaging alterations remain elusive. Proteins neuron-specific enolase (NSE) and ubiquitin C terminal hydrolase 1 are reliable markers for neuronal cell-body damage, both of which have been demonstrated to be increased in serum following mTBI. Therefore, we conducted a longitudinal study to examine relationships between abnormal brain network connectivity and serum neuronal biomarkers and their associations with cognitive recovery following mTBI. Sixty patients were followed-up at 1 week and 3 months post-injury and 41 controls were recruited. Resting-state functional magnetic resonance imaging was used to build a functional connectivity matrix within large-scale intrinsic networks, and their topological properties were analyzed using graph theory measures. We found that, compared with controls, mTBI patients showed significant decreases in a number of nodal characteristics in default mode network (DMN), salience network, and executive network ( p  < 0.05, false discovery rate corrected) at 3 months post-injury. Linear regression analysis found elevated serum NSE in acute phase could predict lower efficiency and degree centrality of anterior DMN at 3 months post-injury. In addition, efficiency and degree centrality of anterior DMN were negatively associated with working memory. Our study showed neuronal injury was associated with alterations in brain network connectivity after mTBI. These findings can facilitate capability to predict the brain functional outcomes and cognitive recovery in mTBI.

Primary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 16 pigs and left untreated for 12 min. During CPR, animals were randomized to receive epinephrine (30 µg/kg) with either esmolol (0.5 mg/kg) or saline (control). Pigs were then observed up to 96 h. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (47 ± 21 vs. 24 ± 10 mmHg at min 5, p < 0.05). In both groups, 7 animals were successfully resuscitated and 4 survived up to 96 h. No significant differences were observed between groups in the total number of defibrillations delivered prior to final resuscitation. Brain histology demonstrated reductions in cortical neuronal degeneration/necrosis (score 0.3 ± 0.5 vs. 1.3 ± 0.5, p < 0.05) and hippocampal microglial activation (6 ± 3 vs. 22 ± 4%, p < 0.01) in the esmolol group compared to control. Lower circulating levels of neuron specific enolase were measured in esmolol animals compared to controls (2[1-3] vs. 21[16-52] ng/mL, p < 0.01). In this preclinical model, β1-blockade during CPR did not facilitate VF termination but provided neuroprotection.

The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren's method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P<0.05) in COVID-19 patients than in controls. Interestingly, within the COVID-19 group, we also observed a further significant increase in dyspnea (Dyspnea Scale and Exercise score: 8.2 ± 0.8; scores ranging from 0 to 10, with higher numbers indicating very severe shortness of breath). These data provide the background for further investigations into the potential role of NSE as a clinical marker of COVID-19 progression., Competing Interests: The authors have declared that no competing interests exist.

Background: PD-1 inhibitors have been routinely used in the treatment of advanced non-small cell lung cancer (NSCLC), and have demonstrated to significantly improve survivorship when combining with other conventional therapies, such as chemotherapy and anti-angiogenesis therapy. PD-L1 is the most commonly used biomarker to select benefiting groups, while not all patients with high PD-L1 expression benefit from immunotherapy. Therefore, identifying other prognostic and predictive biomarkers, including peripheral blood indexes, is essential., Methods: We retrospectively collected medical records and hematological data of 151 patients with advanced NSCLC treated with PD-1 inhibitor-based combination therapy in our hospital. The peripheral blood indexes of interest were NLR, PLR, PAR, Hb, LDH, CEA, and NSE. The association between peripheral blood indexes and treatment responses or survival outcomes was examined by multivariable logistic regression and Cox regression, respectively., Results: The decreased CEA at week 6 (OR = 4.209, 95%CI: 1.287-13.758) or 12 (OR = 7.267, 95%CI: 1.508-35.006) post-treatment was related to a higher disease control rate. The decrease or NLR at week 6 (OR = 3.081, 95%CI: 1.464-6.483) or 12 (OR = 3.304, 95%CI: 1.560-7.001) post-treatment, or CEA at week 12 post-treatment (OR = 2.469, 95%CI: 1.134-5.375), was associated with a higher objective response rate. Patients whose NLR (HR = 0.610, 95%CI: 0.411-0.907) or CEA (HR = 0.477, 95%CI: 0.320-0.710) decreased at week 6 post-treatment tended to have longer progression-free survival, and similar results were found in those with decreased NLR (HR = 0.587, 95%CI: 0.388-0.886) or CEA (HR = 0.406, 95%CI: 0.270-0.609) at week 12 post-treatment. Patients whose CEA (HR = 0.543, 95%CI: 0.339-0.871) or NSE (HR = 0.619, 95%CI: 0.386-0.994) decreased after 6 weeks post-treatment appeared to have longer overall survival, and the same was found for those whoseCEA (HR = 0.620, 95%CI: 0.390-0.986) or NSE (HR = 0.578, 95%CI: 0.353-0.947) was decreased at 12 weeks after treatment., Conclusion: Post-treatment NLR, CEA and NSE changes are suggestive indicators for the prognosis of NSCLC patients after immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Wen, Xia, Du, Wu, Pan, Zhu and Shen.)

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.)

Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Further, appropriateness of study design, analysis, quality, and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through searches of MEDLINE ® , Embase, EBM Reviews, the Cochrane Library, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov. Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department, possibly reducing resource use; however, there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis, and reporting of many of the studies, and identified substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use, and defining standardized, validated, and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.

Background: Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack of information about its oncogenic driver gene mutations., Objectives: We aim to identify the SCLC-related genomic variants that associate with clinical staging and serum protein biomarkers observed in other types of lung cancer., Methods: We screened formalin-fixed paraffin-embedded (FFPE) biopsy tissues of 32 Chinese SCLC patients using the 303 oncogenic driver gene panel generated by Tiling PCR amplification sequencing (tPAS) and analyzed the patients' corresponding serum protein levels of CYFRA21-1 CEA, NSE, and SCCA., Results: In total, we found 147 SCLC-related mutant genes, among these, three important genes ( TP53 , RB1 , KMT2D ) as well as five novel genes LRRK2 , BRCA1 , PTCH1 , ARID2 , and APC that altogether occurred in 90% of patients. Furthermore, increased mutations to 6 genes ( WT1 , NOTCH1 , EPHA3 , KDM6A , SETD2 , ACVR1B ) significantly associated with higher serum NSE levels ( P = 0.0016) and higher clinical stages II + III compared to stage I ( P = 0.06)., Conclusions: Our panel is relatively reliable in detecting the oncogenic mutations of Chinese SCLC patients. Based on our findings, it may be possible to combine SCLC-related mutations and serum NSE for a simple detection of clinical staging., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wang Jin et al.)

Aim: To investigate the clinical value of tumor markers in extrapleural tumor metastasis assessment of newly diagnosed lung cancer patients. Materials & methods: This study retrospectively analyzed 306 patients diagnosed with lung cancer accompanied by tumor metastasis. Patients were grouped into extrapleural tumor metastasis and intrapleural tumor metastasis. Seven serum tumor markers were included for analysis. Results: The area under curves of receiver operating characteristic curve based on binning decision tree algorithm were above 0.8 in both training and validation sets. A scorecard with a score below 3 suggested extrapleural tumor metastasis in newly diagnosed lung cancer patients. Conclusion: The serum tumor marker-derived model is a convenient and fast approach for extrapleural cavity metastasis assessment, which may provide positive implications in newly diagnosed lung cancer patients.

Objectives: Neuron-specific enolase (NSE) is frequently used to predict neurological outcomes in patients with hypoxic brain injury. Hanging can cause hypoxic brain damage, and survivors can suffer from neurological deficits that may impair daily activities. Here, we investigated the utility of the initial serum NSE level as a predictor of neurological outcomes in near-hanging patients with decreased consciousness., Methods: This retrospective multicenter study was conducted in patients who visited the emergency department due to near-hanging injury from October 2013 to February 2019 at three university hospitals in Korea. They were divided into two groups according to the presence of out-of-hospital cardiac arrest. The neurological outcome was determined using the Cerebral Performance Category (CPC) measured at the time of discharge. Multivariate analysis was performed to determine whether initial serum NSE is an independent predictor of neurological outcome., Results: Of the 70 patients included in the study, 44 showed a poor neurological outcome (CPC score = 3-5). Among the 52 patients with cardiac arrest, only 10 (19.2%) were discharged with good neurological outcome (CPC score = 1-2). In the whole cohort, a high serum NSE level was a significant predictor of poor neurological outcome (odds ratio [OR], 1.343; 95% confidence interval [CI], 1.003-1.800, p = 0.048). Among the patients with cardiac arrest, a high serum NSE level was a significant predictor of poor neurological outcome (OR, 1.138; 95% CI, 1.009-1.284, p = 0.036)., Conclusions: In near-hanging patients, a high initial serum NSE level is an independent predictor of poor neurological outcome., Competing Interests: The authors have declared that no competing interests exist.