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Aim: To investigate the performance of the 2021 ERC/ESICM-recommended algorithm for predicting poor outcome after cardiac arrest (CA) and potential tools for predicting neurological recovery in patients with indeterminate outcome., Methods: Prospective, multicenter study on out-of-hospital CA survivors from 28 ICUs of the AfterROSC network. In patients comatose with a Glasgow Coma Scale motor score ≤3 at ≥72 h after resuscitation, we measured: (1) the accuracy of neurological examination, biomarkers (neuron-specific enolase, NSE), electrophysiology (EEG and SSEP) and neuroimaging (brain CT and MRI) for predicting poor outcome (modified Rankin scale score ≥4 at 90 days), and (2) the ability of low or decreasing NSE levels and benign EEG to predict good outcome in patients whose prognosis remained indeterminate., Results: Among 337 included patients, the ERC-ESICM algorithm predicted poor neurological outcome in 175 patients, and the positive predictive value for an unfavourable outcome was 100% [98-100]%. The specificity of individual predictors ranged from 90% for EEG to 100% for clinical examination and SSEP. Among the remaining 162 patients with indeterminate outcome, a combination of 2 favourable signs predicted good outcome with 99[96-100]% specificity and 23[11-38]% sensitivity., Conclusion: All comatose resuscitated patients who fulfilled the ERC-ESICM criteria for poor outcome after CA had poor outcome at three months, even if a self-fulfilling prophecy cannot be completely excluded. In patients with indeterminate outcome (half of the population), favourable signs predicted neurological recovery, reducing prognostic uncertainty., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Jean Baptiste Lascarrou reports financial support was provided by BD. Jean Baptiste Lascarrou reports financial support was provided by Masimo Corporation. Guillaume Geri reports financial support was provided by BD. Guillaume Geri reports financial support was provided by Bard. Claudio Sandroni and Alain Cariou are Associate Editor of Resuscitation If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to develop a double antigen sandwich ELISA (DAgS-ELISA) method for more efficient, accurate, and quantitative detection of total antibodies against Candida albicans enolase1 (CaEno1) for diagnosing invasive candidiasis (IC)., Methods: DAgS-ELISA was developed using recombinant CaEno1 and a monoclonal antibody as the standard. Performance evaluation included limit of detection, accuracy, and repeatability. Dynamic changes in antibody levels against CaEno1 in serum from systemic candidiasis mice were analyzed using DAgS-ELISA. Patient serum samples from IC, Candida colonization, bacterial infections, and healthy controls were analyzed with DAgS-ELISA and indirect ELISA., Results: DAgS-ELISA outperformed indirect ELISA in terms of linear range and test background. In systemic candidiasis mice, a distinctive 'double-peak' pattern in dynamic antibody levels was observed. Additionally, there was a high level of consistency in the positive rates of CaEno1 antibodies detected by both DAgS-ELISA and indirect ELISA. While the positivity rates differed among patient groups, no significant variations in antibody levels were detected among the various positive patient groups., Conclusions: DAgS-ELISA offers a reliable novel approach for IC diagnosis, enabling rapid, accurate, and quantitative detection of CaEno1 antibodies. Further validation and optimization are needed for its clinical application and effectiveness., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the prognostic value of interleukin-6 (IL-6) combined with serum neuron specific enolase (NSE) in arterial atherosclerotic ischemic stroke., Methods: 116 patients with arterial atherosclerotic ischemic stroke admitted to the emergency ward of our Hospital were retrospectively analyzed. According to the score of modified Rankin scale (mRS) at 90 days after discharge, the patients were divided into the poor prognosis group (mRS > 2, n = 32) and the good prognosis group (mRS ≤ 2, n = 84). Activities of Daily Living (ADL) was used to evaluate the level of independence in activities of daily living after treatment., Results: The NIHSS score (14.91 ± 5.20 vs. 9.43 ± 4.30, P < 0.001), IL-6 (11.30 ± 3.11 vs. 6.75±1.28, P < 0.001) and NSE levels (12.47 ± 4.69 vs. 6.42 ± 1.32, P<0.001) in poor prognosis group were higher than those in the good prognosis group. At 90 days post-discharge, 100 % of the good prognosis group had ADL scores over 60, while in the poor prognosis group, 46.88 % scored 40-60, 40.63 % scored 20-40, 9.38 % scored under 20, and 3.13 % died. The AUC of NSE was 0.906 (95 % CI: 0.847-0.965, P < 0.001), the best cut-off value was 7.445 ng/mL, and the sensitivity and specificity were 75.0 % and 82.1 %, respectively. The AUC for IL-6 combined with NSE increased to 0.965 (95 %CI: 0.934-0.997, P < 0.001), and the sensitivity and specificity increased to 80.2 % and 92.9 %, respectively., Conclusion: IL-6 ≥ 6.805 pg/mL and NSE ≥ 7.445 ng/mL were independently associated with poor prognosis in patients with AIS, and the combined testing of the two indicators had a higher predictive value. These results suggested that the combined assay of IL-6 and NSE could be a novel marker for predicting poor prognosis in AIS., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Objective : To explore the association of serum transactive response DNA binding protein 43 (TDP-43) with 28-day poor neurologic outcome in patients with return of spontaneous circulation (ROSC) after cardiac arrest. Methods : We performed a study between January and December 2023. Eligible patients with ROSC following cardiac arrest were enrolled. Their baseline characteristics were collected, and serum levels of TDP-43, tumor necrosis factor-α, interleukin-6 and 10, C-reactive protein, and neuron-specific enolase (NSE) at 24 h after ROSC were measured. The neurologic function was assessed by the cerebral performance category scores on day 28 after ROSC. Results : A total of 92 patients were included, with 51 and 41 patients in the good and poor neurologic outcome groups, respectively. Serum TDP-43 was significantly higher in the poor than the good neurologic outcome group ( P < 0.05). Univariate and multivariate logistic regression analyses showed that TDP-43, Witnessed CA, IL-6, and NSE were associated with poor 28-day neurologic outcome (all P < 0.05). Restricted cubic spline analysis revealed that TDP-43 at the serum level of 11.64 pg/mL might be an ideal cutoff value for distinguishing between good and poor neurologic outcomes. Area under curve of serum TDP-43 (AUC = 0.78) was close to that of serum NSE (AUC = 0.82). A dynamic nomogram prediction model that combined TDP-43, Witnessed CA, IL-6, and NSE was constructed and validated. Conclusion : Elevated serum TDP-43 level was associated with and could be used together with Witnessed CA, IL-6, and NSE to predict poor 28-day neurologic outcome in patients after ROSC following cardiac arrest., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

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.

Intact-mass spectrometry has huge potential for clinical application, as it enables both quantitative and qualitative analysis of intact proteins and possibly unlocks additional pathophysiological information via, e.g., detection of specific post-translational modifications (PTMs). Such valuable and clinically useful selectivity is typically lost during conventional bottom-up mass spectrometry. We demonstrate an innovative immunoprecipitation protein enrichment assay coupled to ultrahigh performance liquid chromatography quadrupole time-of-flight high resolution mass spectrometry (UPLC-QToF-HRMS) for the fast and simple identification of the protein tumor marker Neuron Specific Enolase Gamma (NSEγ) at low endogenous concentrations in human serum. Additionally, using the combination of immunoaffinity purification with intact mass spectrometry, the presence of NSEγ in an acetylated form in human serum was detected. This highlights the unique potential of immunoaffinity intact mass spectrometry in clinical diagnostics.

Background: The aim of the study is to assess the value of beta-2-microglobulin (B2M) and neuron-specific enolase (NSE) as prognostic factors in the population of patients over 65 years of age with frailty hospitalized due to acute coronary syndrome (ACS)., Methods: Patients aged ≥65 years with ACS were included. Assessment of frailty was carried out using the FRAIL scale. The measurement of NSE and B2M was carried out three times during hospitalization: (1) at the time of admission, (2) on the second day of hospitalization, (3) on the seventh day of hospitalization, or the day of discharge if it was before the seventh day. The primary endpoint was all-cause mortality, and the secondary endpoint was unscheduled rehospitalization., Results: Of the 127 patients, frailty was identified in 39.3%. Multivariate analysis of variance showed significantly higher levels of NSE ( P  = 0.012) and B2M ( P  < 0.001) in patients with frailty compared to the nonfrail group and significant changes in marker levels during hospitalization - decreased NSE ( P  < 0.001) and increased B2M levels ( P  < 0.001). Elevated B2M-1 level was an independent marker of the occurrence of frailty [odds ratio (OR), 1.98 (1.09-4.00); P  = 0.044], and the optimal cutoff point for the diagnosis of frailty was 2.85 mg/l [area under the curve (AUC), 0.718 (0.632-0.795)] with sensitivity 52% and specificity 84.4% ( P  < 0.001). Elevated NSE-3 level was associated with all-cause mortality, and each 1 ng/ml increase in NSE-3 increased the risk of death by 1.07-fold [OR, 1.07 (1.03-1.10]). Meanwhile, elevated B2M-3 level was associated with unscheduled rehospitalization, and each 1 mg/l increase in B2M-3 increased the risk of unscheduled rehospitalization by 1.21-fold [OR, 1.21 (1.03-1.42)]. The Harrell's C-index for all-cause mortality was higher for NSE-3 [0.820 (95% confidence interval {CI}, 0.706-0.934)] compared to frailty assessed by the FRAIL scale [0.715 (95% CI, 0.580-0.850)], which means that additional NSE-3 assessment may improve the prediction of all-cause mortality. However, Uno's C-Statistic analysis showed that the difference was not statistically significant (Pr>chi-square 0.556). Harrell's C-index for unscheduled rehospitalization was higher for frailty assessed by the FRAIL scale compared to B2M-3., Conclusion: Monitoring NSE and B2M marker levels in patients over 65 years of age with frailty and ACS does not provide additional benefits in terms of prognostic ability compared to tests assessing frailty. B2M, assessed upon hospital admission and monitoring NSE and B2M levels during hospitalization may be considered in the diagnosis of frailty and risk stratification in a group of patients for whom currently available frailty diagnostic tools cannot be used., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis., Methods: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables., Results: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1., Conclusions: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained., Competing Interests: Declaration of Competing Interests The author has no financial or other conflicts of interest to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

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.

Background: Biomarkers play a role in identifying, managing, and predicting cancer outcomes. In lung cancer, they are used at various time points. Doubts remain regarding their accuracy for differential diagnosis and histological subtyping. A diagnostic test study was conducted. It included malignant lesions and controls with benign lesions. Before lung biopsy, all patients had the following biomarkers measured in serum (Pro-GRP,NSE,CYFRA21-1,SCC-Ag,CEA)., Methods: The predictive capacity of serum biomarkers was evaluated to discriminate between lung cancer and benign pathology. The accuracy was also assessed for distinguishing between SCLC and NSCLC and explored their ability to perform histological subtyping., Results: 93 patients were included, 60 with lung cancer, 33 with benign pathology. Pro-GRP and NSE were elevated in SCLC compared with NSCLC or nonmalignant disease. The most accurate for differentiating between malignant and benign pathology were CEA and CYFRA21-1. Pro-GRP had a poor predictive capacity for distinguishing NSCLC from SCLC. However, combined with CEA and CYFRA21-1, performance improved. For SCLC, the diagnostic capacity of Pro-GRP increased by combining with biomarkers, such as NSE/CYFRA21-1., Conclusions: Biomarkers lacked the sensitivity and specificity for independent differential diagnosis or histological subtyping. However, the observed patterns in biomarker levels associated with specific histological subtypes suggest potential utility in a multi-biomarker approach or in conjunction with other diagnostic tools. This insight could guide future research to improve diagnostic accuracy and personalized treatment strategies in lung cancer.

Purpose: To characterize and compare clinical and immunological features of para(p)-autoimmune retinopathy (AIR) and non-para(np)-AIR and to assess the clinical significance of the presence of serum anti-retinal antibodies (ARAs)., Methods: We retrospectively reviewed 48 Chinese patients with p-AIR or np-AIR who took comprehensive ophthalmic examinations and lab tests of the presence of serum ARAs., Results: p-AIR patients differed from np-AIR patients in terms of disease progression, ocular inflammation, findings of OCT, FFA, and presence of ARAs. No significant difference was found in the band number of serum ARAs between AIR patients and healthy controls. The prevalence of antibodies to recoverin and ɑ-enolase in the sera of p-AIR was significantly higher than that of the healthy individuals., Conclusion: While having many similar clinical signs, patients with p-AIR or np-AIR nevertheless displayed unique characteristics. Detection of ARAs subtypes, rather than their quantity, may be helpful in evaluating the conditions in the verified instances.

Neuron-specific enolase (NSE) derived from neurons and peripheral neuroendocrine cells is a biomarker for neuroendocrine tumors and for prognostication in comatose cardiac arrest survivors. However, as platelets and erythrocytes contain NSE, hemolysis causes falsely elevated NSE. We used native serum and hemolysate derived from the same patients to make serial dilutions, and subsequently measured NSE (mNSE) and hemolytic index (HI) in each dilution. An algorithm suitable for the laboratory information system was developed based on the mNSE, HI and the estimated gradient of hemolytic interference from 30 patients. We estimated the associated uncertainty of the corrected NSE (cNSE) results based on the observed range of the gradient and derived an equation for cNSE for samples with limited hemolysis (i.e. 5 < HI ≤ 30): cNSE = mNSE - HI × (0.34 ± 0.23) µg/L. By semi-quantitatively grading the contribution from limited hemolysis, a texted result noting the hemolysis-associated degree of uncertainty can accompany the cNSE result. The major challenge of hemolysis when using serum NSE as a biomarker can be managed using an automated algorithm for correction of NSE results based on degree of hemolysis. However, laboratorians and clinicians should be aware of the limitations associated with in vivo hemolysis.

Purpose: Infantile epileptic spasms syndrome (IESS) with epileptic spasms as the main seizure type, is treated with adrenocorticotropic hormone (ACTH). This study, for the first time, examines the effects of epileptic spasms and ACTH on blood-brain barrier (BBB) permeability in patients with IESS of unknown etiology., Methods: We prospectively evaluated the changes in BBB permeability in patients with IESS of unknown etiology at the Saitama Children's Medical Center between February 2012 and February 2024. We compared the levels of serum-albumin, cerebrospinal fluid (CSF)-albumin, Q-albumin, and CSF-neuron-specific enolase (NSE) before and after ACTH therapy. We also assessed the correlation between the frequency of epileptic spasms and these markers., Results: Overall, 16 patients with IESS (8 males) were included in the study. The median age at IESS onset was 5 (range, 2-9) months. The median duration between the epileptic spasms onset and the serum and CSF sample examination before ACTH therapy was 26 (range, 1-154) days. After ACTH therapy, CSF-albumin and Q-albumin levels significantly decreased (CSF-albumin: 13.5 (9.0-32.0) mg/dL vs 11.0 (7.0-19.0) mg/dL, p = 0.001. Q-albumin: 3.7× 10 -3 (2.2 × 10 -3 -7.3 × 10 -3 ) vs 2.8× 10 -3 (1.9 × 10 -3 -4.5 × 10 -3 ), p = 0.003). No correlation was observed between the epileptic spasms frequency and levels of serum-albumin, CSF-albumin, Q-albumin, and CSF-NSE (Spearman's coefficient: r = 0.291, r = 0.141, r = 0.094, and r = -0.471, respectively)., Conclusion: ACTH therapy is one of the factors that play a role in restoring BBB permeability in patients with IESS of unknown etiology. Our findings may be useful in elucidating the mechanism of ACTH action and IESS pathophysiology., Competing Interests: Declaration of competing interest Shin-ichiro Hamano has received funds for speaker honoraria and travel from Eisai Co. Ltd., Daiichi Sankyo Co. Ltd., and UCB Japan Co. Ltd. Akira Oka has received funds for speaker honoraria and travel from Eisai Co. Ltd. and Nippon Shinyaku Co. Ltd. Kenjiro Kikuchi has received research funding from Syneos health clinical Co. Ltd. for clinical trial of Zogenix. The other authors have nothing to disclose conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lung cancer is the main cancer that endangers human life worldwide, with the highest mortality rate. The detection of lung tumor markers is of great significance for the early diagnosis and subsequent treatment of lung cancer. In this study, a vertical graphene field effect transistor (VGFET) immunosensor based on graphene/C 60 heterojunction was created to offer quantitative detections for the lung tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), and neuron-specific enolase (NSE). The experimental results showed that the sensitive range for standard antigen is between 1 pg/ml to 100 ng/ml, with a limit of detection (LOD) of 5.6 amol/ml for CEA, 33.3 amol/ml for Cyfra 21-1 and 12.8 amol/ml for NSE (1 pg/ml for all). The detection accuracy for these tumor markers was compared with the clinically used method for clinical patients on serum samples. Results are highly consistent with clinically used immunoassay in its efficient diagnosis concentration range. Subsequently, the mesoporous silica nanospheres (MSNs) with an average size of 90 nm were surface modified with glutaraldehyde, and a second antibody was assembled on MSNs, which fixes nanospheres on the antigen and amplified the field effect. The LODs for three markers are 100 fg/ml (0.56 amol/ml for CEA) under optimal circumstances of detection. This result indicates that specific binding to MSNs enhances local field effects and can achieve higher sensing efficiency for tumor marker detection at extremely low concentrations, providing effective assistance for the early diagnosis of lung cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.)

Neuron-specific enolase (NSE) is one of the biomarkers used as an indicator of brain disorder, but since it is also found in blood cell components, there is a concern that a spurious increase in NSE may occur after cardiovascular surgery, where cardiopulmonary bypass (CPB) causes hemolysis. In the present study, we investigated the relationship between the degree of hemolysis and NSE after cardiovascular surgery and the usefulness of immediate postoperative NSE values in the diagnosis of brain disorder. A retrospective study of 198 patients who underwent surgery with CPB in the period from May 2019 to May 2021 was conducted. Postoperative NSE levels and Free hemoglobin (F-Hb) levels were compared in both groups. In addition, to verify the relationship between hemolysis and NSE, we examined the correlation between F-Hb levels and NSE levels. We also examined whether different surgical procedures could produce an association between hemolysis and NSE. Among 198 patients, 20 had postoperative stroke (Group S) and 178 had no postoperative stroke (Group U). There was no significant difference in postoperative NSE levels and F-Hb levels between Group S and Group U (p = 0.264, p = 0.064 respectively). F-Hb and NSE were weakly correlated (r = 0.29. p < 0.01). In conclusion, NSE level immediately after cardiac surgery with CPB is modified by hemolysis rather than brain injury, therefore it would be unreliable as a biomarker of brain disorder., (© 2023. The Author(s).)

Introduction: Brain dysfunction in sepsis is known as sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Neuron specific enolase (NSE) may serve as an important neurocritical biomarker for detection and longitudinal monitoring in SAE patients. Our systematic review and meta-analysis will aim to explore the diagnostic and prognostic value of serum NSE in SAE patients. Currently, no systematic review and meta-analysis have been assessed that NSE as a biomarker of SAE., Methods and Analysis: We will conduct a systematic review and meta-analysis of serum NSE for the diagnostic and prognostic value of SAE patients. The primary objective is to evaluate the diagnostic accuracy of serum NSE as an independent biomarker for SAE. The secondary objective is to determine the prognostic strength of serum NSE as an independent biomarker of mortality in septic patients determine. We will perform a systematic search and descriptive review using the MEDLINE database and the PubMed interface. We will assign two independent reviewers to review all collected titles and associated abstracts, review full articles, and extract study data. We will use the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2) assessment tool according to the recommendation by the Cochrane Collaboration to evaluate quality and risk of bias of the selected studies. Subgroup and sensitivity analyses will also be used to assess heterogeneity. Review Manager version 5.4 and Stata16.0. will be used for statistical analysis., Ethics and Dissemination: The meta-analysis will provide ICU physicians with the most current information to predict which patients are at risk of SAE and take corresponding intervention measures to reduce morbidity and ameliorate neurological outcomes. There is no need for ethics approval for this review. The findings will be disseminated in a peer-reviewed journal., Trial Registration Number: CRD42023398736., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Limited evidence exists for prognostic performance of biomarkers in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with extracorporeal CPR (ECPR). We hypothesized that (1) the time course and (2) prognostic performance of biomarkers might differ between CPR and ECPR in a sub-analysis of Prague-OHCA study., Methods: Patients received either CPR (n = 164) or ECPR (n = 92). The primary outcome was favorable neurologic survival at 180 days [cerebral performance category (CPC) 1-2]. Secondary outcomes included biomarkers of neurologic injury, inflammation and hemocoagulation., Results: Favorable neurologic outcome was not different between groups: CPR 29.3% vs. ECPR 21.7%; p = 0.191. Biomarkers exhibited similar trajectories in both groups, with better values in patients with CPC 1-2. Procalcitonin (PCT) was higher in ECPR group at 24-72 h (all p < 0.01). Neuron-specific enolase (NSE), C-reactive protein and neutrophil-to-lymphocyte ratio did not differ between groups. Platelets, D-dimers and fibrinogen were lower in ECPR vs. CPR groups at 24-72 h (all p < 0.001). ROC analysis (24-48-72 h) showed the best performance of NSE in both CPR and ECPR groups (AUC 0.89 vs. 0.78; 0.9 vs. 0.9; 0.91 vs. 0.9). PCT showed good performance specifically in ECPR (0.72 vs. 0.84; 0.73 vs. 0.87; 0.73 vs. 0.86). Optimal cutoff points of NSE and PCT were higher in ECPR vs. CPR., Conclusions: Biomarkers exhibited similar trajectories although absolute values tended to be higher in ECPR. NSE had superior performance in both groups. PCT showed a good performance specifically in ECPR. Additional biomarkers may have modest incremental value. Prognostication algorithms should reflect the resuscitation method., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Dr. Belohlavek reported receiving lecture honoraria from the Getinge and Resuscitec Companies. No other authors reported disclosures.’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To assess the ability of clinical examination, biomarkers, electrophysiology and brain imaging, individually or in combination to predict good neurological outcomes at 6 months after CA., Methods: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0, which included adult out-of-hospital cardiac arrest (OHCA) patients (≥18 years). Good outcome predictors were defined as both pupillary light reflex (PLR) and corneal reflex (CR) at admission, Glasgow Coma Scale Motor score (GCS-M) >3 at admission, neuron-specific enolase (NSE) <17 µg/L at 24-72 h, a median nerve somatosensory evoked potential (SSEP) N20/P25 amplitude >4 µV, continuous background without discharges on electroencephalogram (EEG), and absence of anoxic injury on brain CT and diffusion-weighted imaging (DWI)., Results: A total of 1327 subjects were included in the final analysis, and their median age was 59 years; among them, 412 subjects had a good neurological outcome at 6 months. GCS-M >3 at admission had the highest specificity of 96.7% (95% CI 95.3-97.8), and normal brain DWI had the highest sensitivity of 96.3% (95% CI 92.9-98.4). When the two predictors were combined, the sensitivities tended to decrease (ranging from 2.7-81.1%), and the specificities tended to increase, ranging from81.3-100%. Through the explorative variation of the 2021 European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) prognostication strategy algorithms, good outcomes were predicted, with a specificity of 83.2% and a sensitivity of 83.5% in patients by the algorithm., Conclusions: Clinical examination, biomarker, electrophysiology, and brain imaging predicted good outcomes at 6 months after CA. When the two predictors were combined, the specificity further improved. With the 2021 ERC/ESICM guidelines, the number of indeterminate patients and the uncertainty of prognostication can be reduced by using a good outcome prediction algorithm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

The purpose of this study was to explore the relationship between the MYCN gene, serum neuron-specific enolase (NSE), urinary vanillylmandelic acid (VMA) levels, and neuroblastoma pathological features and prognosis. Ninety-four children with neuroblastoma treated in the hospital were selected to compare the differences in MYCN gene amplification, serum NSE, and urinary VMA levels in children with different clinicopathological features and prognoses. The proportion of children with MYCN gene copy number ≥10 in INSS stage 3-4 was higher than that of children with INSS stage 1-2 (P < 0.05); the proportion of children with MYCN gene copy number ≥10 in high-risk children in the COG risk stratification was higher than that of children with intermediate and low risk (P < 0.05); the serum NSE of children aged >12 months higher than that of children aged ≤12 months (P < 0.05); serum NSE of children with tumors >500 cm3 higher than that of children with tumors ≤500 cm3 (P < 0.05); serum NSE and urinary VMA of children with INSS staging of stages 3-4 were higher than that of children with stages 1 to 2 (P < 0.05); serum NSE and urinary VMA in children with lymph node metastasis were higher than that of children without lymph node metastasis (P < 0.05); serum NSE of children with MYCN gene copy number ≥10 was higher than that of children without lymph node metastasis (P < 0.05); the proportion of children with MYCN gene copy number ≥10 who died, and the percentages of serum NSE and urinary VMA were higher than those of the surviving children (P < 0.05). MYCN gene amplification and serum NSE and urinary VMA levels were related to the age, tumor size, INSS stage, COG stage, lymph node metastasis, and prognosis of the children with neuroblastoma.

Introduction: We evaluated the prognostic role of pre-salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE)., Materials and Methods: Patients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery. Cox regression and logistic regression models tested the relationship between biochemical recurrence-free survival (BFS), 6- and 12-month biochemical recurrence (BCR), and several independent variables, including biomarkers., Results: 153 consecutive patients were analyzed. In the univariable Cox regression analysis, none of the biomarkers achieved predictor status (AP: hazard ratio [HR] = 1.03, 95% CI 0.99, 1.01; p = 0.19; CEA: HR = 1.73, 95% CI 0.94, 1.21; p = 0.34; LDH: HR = 1.01, 95% CI 1.00, 1.01; p = 0.05; NSE: HR = 1.02, 95% CI 0.98, 1.06; p = 0.39). The only independent predictor of BFS was the number of positive lesions on PSMA PET (HR = 1.17, 95% CI 1.02, 1.30; p = 0.03). The number of positive lesions was confirmed as independent predictor for BCR within 6 and 12 months (BCR < 6 months: odds ratio [OR] = 1.1, 95% CI 1.0, 1.3; p = 0.04; BCR < 12 months: OR = 1.1, 95% CI 1.0, 1.3; p = 0.04)., Conclusion: The assessment of AP, CEA, LDH, and NSE before salvage PSMA-RGS showed no prognostic impact. Further studies are needed to identify possible predictors that will optimize patient selection for salvage PSMA-RGS., (© 2024. The Author(s).)

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.

Purpose: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure., Methods: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed., Results: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported., Conclusion: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study., (© 2024. The Author(s).)

Objectives: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED., Methods: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI., Results: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively., Conclusions: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

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.)

The serum levels of pro-gastrin-releasing peptide (proGRP), neuron-specific enolase (NSE), and chromogranin A (CgA) were studied in 69 patients with small cell lung cancer and 50 apparently healthy donors. A significant increase of all studied biochemical markers was revealed in small cell lung cancer patients, while the highest diagnostic efficiency was demonstrated by proGRP compared to NSE and CgA. ProGRP is a promising biochemical marker of small cell lung cancer, especially sensitive in patients with distant metastases (in the brain, liver, and bones)., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Objectives: This research aims to study the prognostic role of serum S100 as a predictor of mortality in vascular and traumatic brain injuries., Methods: This prospective cohort study involved 219 patients. In the blood serum, neuron-specific markers (S100, NSE) and glucose, acid-base state and gas composition of arterial blood were obtained at admission, on the 3rd, 5th and 7th days of patients' stay in the intensive care unit., Results: The most significant risk factor for an unfavorable outcome is the marker S100 with a cut-off point of 0.2 mcg/l. The analysis results indicate a statistically significant direct relationship between S100 > 0.2 mcg/l and NSE ≥ 18.9 ng/ml compared to other variables, while the chance ratio (OR) is 11.9 (95%CI:3.2927-1.6693;). With blood sugar increase above 7.4 mmol/l, the OR is 3.82 (95% CI: 2.1289-0.5539;); with a Glasgow scale below 13 points, the OR is 3.69 (95% CI: 2.1316-0.4819;); with an increase in pCO2 < 43.5 mm Hg, the OR was 3.15 (95% CI: 1.8916- 0.4062;). The obtained model certainty measure according to pseudo R2 Nagelkerke criterion is 263.5, showing the excellent quality of the mathematical model's predictive ability. The developed prognostic model, including the dependent variable S100 and independent variables as predictors of a poor outcome of NSE, pCO2, GCS and Hb, reached a cut-off point of 84.51%, AUC - 0.88 with high levels of sensitivity and specificity: 91.89% and 64.14%, respectively., Novelty: This model can be used to predict the outcome in patients with acute cerebral pathology.

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).)

Brain dysfunction is a prerequisite for critical complications in children with hand, foot, and mouth disease (HFMD). Aquaporin 4 (AQP-4) may be involved in the pathological process of cerebral oedema and injury in children with severe and critical HFMD. This study aimed to assess the association of AQP-4 with the severity of enterovirus 71 (EV71)-associated HFMD. Children with EV71-infected HFMD were divided into a common group (clinical stage 1), a severe group (clinical stage 2), and a critical group (clinical stage 3) according to Chinese guidelines. The levels of AQP-4, interleukin-6 (IL-6), norepinephrine (NE), and neuron-specific enolase (NSE) before and after treatment were tested. Serum AQP-4, IL-6, NE, and NSE levels showed significant differences among the critical, severe, and common groups before and after treatment (P < 0.01). No significant differences in AQP-4 levels in cerebrospinal fluid (CSF) were observed between the critical and severe groups before and after treatment, but the CSF AQP-4 levels in these two groups were higher than those in the common group before treatment (P < 0.01). Serum AQP-4 levels, but not CSF AQP-4 levels, closely correlated with serum IL-6, NE, and NSE levels. These results suggest that the level of AQP-4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of EV71-associated HFMD., (© 2019 Wiley Periodicals, Inc.)

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: Neuron-specific enolase (NSE) is released into serum when nerve cells are damaged, and the levels thereof are used to determine neurological prognosis in patients who have suffered cardiac arrest or stroke. Delayed neuropsychiatric sequelae (DNS), a major complication of carbon monoxide poisoning (COP), can be caused by inflammatory response which is a mechanism of neuronal injury in cardiac arrest and stroke. NSE is known as a predictor of neurological prognosis in ischemic brain injury after cardiac arrest, and it is also reported as a predictor of DNS in acute COP. When serum NSE is measured serially in cardiac arrest patients, the best time to predict neurological prognosis is known at 48-72 h, but there are no studies analyzing serial serum NSE in acute COP. Thus, we explored whether serum NSE levels measured three times at 24 h intervals after COP predicted the development of DNS., Methods: This prospective observational study was conducted on patients treated for COP from May 2018 to April 2020 in a tertiary care hospital in Korea. Neuron-specific enolase levels were assessed 24, 48, and 72 h after presentation at hospital. We used logistic regression to explore the association between NSE levels and DNS development., Results: The NSE level was highest at 48 h, and the difference between the DNS group and the non-DNS group was greatest on the same time point. On multivariable logistic regression analysis, the NSE level at 48 h of >20.98 ng/mL (odds ratio [OR], 3.570; 95% confidence interval [CI], 1.412-9.026; P = .007) and the initial Glasgow Coma Scale (GCS) score of <9 (OR, 4.559; 95% CI, 1.658-0.12.540; P = .003) was statistically significant for DNS development., Conclusion: Early identification of those who will experience DNS in acute COP patients is clinically important for deciding treatment. In this study, we revealed that NSE level of >20.98 ng/mL at 48 h time point can be used as an independent predictor of DNS (OR, 3.570; 95% CI, 1.412-9.026; P = .007; AUC, 0.648).

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.

Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15 mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2 mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48 h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48 h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

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).)