Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.

OBJECTIVE: An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). METHODS: A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. RESULTS: ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CONCLUSION: CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.

Promising predictors of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus.

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.

Discussion of spinal cord neurons apoptosis and neuroprotection mechanism of NGF gene transfection mediated by recombinant adenovirus in EAE mice.

To investigate the spinal cord neuron apoptosis and neuroprotective mechanism of nerve growth factorganismsor (NGF) gene mediated by recombinant adenovirus (Ad-NGF) via peripheral transfection in mice with experimental autoimmune encephalomyelitis (EAE). Forty healthy female C57BL/6 mice were randomly divided into a control group, adenovirus (AdV) group, EAE group, and Ad-NGF transfection group; the control group received no treatment; the AdV group received adenovirus injection via the tail vein; the EAE and Ad-NGF transfection groups were induced with experimental autoimmune encephalomyelitis (EAE) using myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), Ad-NGF transfection group received Ad-NGF injection via the tail vein, and daily neurological impairment scores were obtained. AQThe TUNEL method was employed to observe spinal neuron apoptosis in each group of mice; protein immunoblotting (western blot) and RT-PCR were used to measure NGF levels in the spinal cord tissues of each group, and western blotting was used to assess levels of cleaved caspase-3, Bax, and Bcl-2. ELISA and RT-PCR were employed to detect protein and mRNA levels of neuron-specific enolase (NSE) in spinal cord tissues, respectively. The control group and AdV mice did not develop symptoms. Compared to the EAE group, in the Ad-NGF transfection group, neurological function scores, TUNEL-positive cell counts, the ratio of NeuN + TUNEL to NeuN, levels of Bax and cleaved caspase-3 apoptotic proteins were significantly reduced, while Bcl-2 protein expression was increased. Expression levels of NGF, NGF-mRNA, NSE, and NSE-mRNA in spinal cord tissues were significantly elevated (P < 0.01). Immunofluorescence labeling revealed a significant punctate aggregation of apoptotic cells in spinal neurons of the EAE group, while the aggregation phenomenon was less pronounced in the Ad-NGF transfection group. Ad-NGF transfected by the periphery has a protective effect on spinal cord neurons in EAE mice by up-regulation NGF level, down-regulating apoptotic protein Caspase-3 in spinal cord neurons, inhibiting spinal cord neuron apoptosis and promoting NSE expression.

Successful Target Temperature Management After Cardiac Arrest: A Case Report and a Review of the Literature.

A 20-year-old female was admitted to the hospital after a successful resuscitation from a cardiac arrest due to ventricular fibrillation. She had no prior medical history. The patient was rescued from her house, brought to the hospital with sinus rhythm, sedated, in a coma. Electrocardiography showed no modifications other than the ventricular extrasystoles. Computed tomography showed an epicranian hematoma from the fall that occurred during the cardiac arrest, a heart with a thickened interventricular septum, and the other organs being within physiological limits. Magnetic resonance imaging showed late hypoxic leukoencephalopathy with a level of the white matter of the semioval centers, radiating corona, splenium corpus callosum, and internal capsular posterior arm with extension to the cerebral peduncles. The patient achieved a good neurological outcome with target temperature management and had small neurological improvements every day after resuming spontaneous breathing. After a long intensive care and hospitalization period of six weeks, she was discharged, able to resume her societal status and be a fully recovered individual.

Evaluation of silent brain injury in patients undergoing aorto-ostial coronary stent implantation.

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.

Post-mortem utility of Neuron Specific Enolase (NSE) and Calcium Binding Protein B (S100B) for differentiating traumatic brain injury from other causes of death.

In forensic pathology, identifying causes of death in traumatic brain injuries (TBIs) devoid of observable signs presents a significant challenge. Post-mortem biochemistry plays a crucial role in forensic medicine, particularly in determining causes of death in TBIs that lack macroscopic or histopathological evidence. This study aimed to evaluate the utility of Neuron Specific Enolase (NSE) and S100 Calcium Binding Protein B (S100B) in post-mortem serum and cerebrospinal fluid (CSF) as markers for TBI. The relationship of these biochemical markers with survival time and post-mortem interval was also studied. The study sample consisted of 63 cases each from the TBI and the Non-TBI (NTBI) group. The NTBI group comprised of deaths due to mechanical asphyxia, myocardial infarction and isolated trunk trauma. While serum S100B and CSF NSE emerged as a promising marker for TBI, CSF S100B failed to differentiate TBI from the other causes of death. The absence of an association between the level of markers and survival time or post-mortem interval in TBIs highlights the limitations of these biomarkers in such contexts. This study underscores the potential of biochemical markers like serum S100B and CSF NSE in identifying TBI deaths, aiding forensic diagnoses where there are evidentiary limitations in traditional methods. Further research exploring additional markers and body fluids could enhance diagnostic precision in forensic neuropathology.

Changes in short-chain fatty acids affect brain development in mice with early life antibiotic-induced dysbacteriosis.

Background: Early enteral nutrition and the gut microbiota profoundly influence neonatal brain development, with short-chain fatty acids (SCFAs) from the microbiota playing a pivotal role. Understanding the relationship between dysbiosis, SCFAs, and brain development is crucial. In this study, we investigated the impact of antibiotics on the concentration of SCFAs in neonatal feces. Additionally, we developed a model of gut dysbiosis in neonatal mice to examine the potential relationship between this imbalance, SCFAs production, and brain function development. Methods: We measured the SCFAs content in the feces of two groups of neonates, categorized based on whether antibiotics were used, and conducted the Neonatal Behavioral Neurological Assessment (NBNA) test on all neonates. Then we evaluated fecal SCFAs levels in neonates and neonatal mice post-antibiotic treatment using liquid chromatography-mass spectrometry (LC-MS) analysis. Morris water maze (MWM) tests assessed behavioral performance, and western blot analysis examined brain tissue-related proteins-neuron-specific enolase (NSE), ionized calcium binding adaptor molecule-1 (IBA1), and myelin basic proteins (MBP). Results: The use of antibiotics did not affect the NBNA scores of the two groups of neonates, but it did reduce the SCFAs content in their feces. Antibiotic administration induced gut dysbiosis in mice, resulting in decreased IBA1 and MBP expression. Interventions to restore gut microbiota ameliorated these effects. Mice with dysbiosis displayed cognitive deficits in the MWM test. SCFAs levels decreased during dysbiosis, and increased upon microbiota recovery. Conclusions: Neonatal dysbiosis affects the microbiota-gut-brain axis, impairing cognitive function and nervous system development. Reduced SCFAs may contribute significantly to these alterations.

Serum tumor markers: potential indicators for occult lymph node metastasis in clinical T1 - 2N0M0 small cell lung cancer patients.

In their letter-to-the-editor entitled "Letter to the Editor: Incidence rate of occult lymph node metastasis in clinical T1 - 2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study", Prof. Chen et al. provided insightful comments and suggestions on our original study. We appreciate the authors' feedback and have conducted a preliminary exploration of the predictive value of serum tumor markers (TMs) for occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients. The results indicate that neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), and squamous cell carcinoma antigen (SCC) have potential predictive value for detecting OLM in cT1 - 2N0M0 SCLC patients. Additionally, further exploration and confirmation through prospective, large-scale studies with robust external validation are needed.

Neuron-specific enolase as a prognostic biomarker in acute ischemic stroke patients treated with reperfusion therapies.

Introduction: Ischemic stroke is a significant global health concern, with reperfusion therapies playing a vital role in patient management. Neuron-specific enolase (NSE) has been suggested as a potential biomarker for assessing stroke severity and prognosis, however, the role of NSE in predicting long-term outcomes in patients undergoing reperfusion therapies is still scarce. Aim: To investigate the association between serum NSE levels at admission and 48 h after reperfusion therapies, and functional outcomes at 90 days in ischemic stroke patients. Methods: This study conducted a prospective cross-sectional analysis on consecutive acute ischemic stroke patients undergoing intravenous fibrinolysis and/or endovascular thrombectomy. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days post-stroke and two groups were defined according to having unfavorable (mRS3-6) or favorable (mRS0-2) outcome. Demographic, clinical, radiological, and laboratory data were collected, including NSE levels at admission and 48 h. Spearman's coefficient evaluated the correlation between analyzed variables. Logistic regression analysis was performed to verify which variables were independently associated with unfavorable outcome. Two ROC curves determined the cut-off points for NSE at admission and 48 h, being compared by Delong test. Results: Analysis of 79 patients undergoing reperfusion treatment following acute stroke revealed that patients with mRS 3-6 had higher NIHSS at admission (p < 0.0001), higher NIHSS at 24 h (p < 0.0001), and higher NSE levels at 48 h (p = 0.008) when compared to those with mRS 0-2. Optimal cut-off values for NSE0 (>14.2 ng/mL) and NSE48h (>26.3 ng/mL) were identified, showing associations with worse clinical outcomes. Adjusted analyses demonstrated that patients with NSE48h > 26.3 ng/mL had a 13.5 times higher risk of unfavorable outcome, while each unit increase in NIHSS24h score was associated with a 22% increase in unfavorable outcome. Receiver operating characteristic analysis indicated similar predictive abilities of NSE levels at admission and 48 h (p = 0.298). Additionally, a strong positive correlation was observed between NSE48h levels and mRS at 90 days (r = 0.400 and p < 0.0001), suggesting that higher NSE levels indicate worse neurological disability post-stroke. Conclusion: Serum NSE levels at 48 h post-reperfusion therapies are associated with functional outcomes in ischemic stroke patients, serving as potential tool for patient long-term prognosis.

Efficient CdIn2S4/MgIn2S4 heterojunction for ultrasensitive detection of lung cancer marker neuron-specific enolase.

In this work, a photoelectrochemical (PEC) immunosensor was constructed for the ultrasensitive detection of lung cancer marker neuron-specific enolase (NSE) based on a microflower-like heterojunction of cadmium indium sulfide and magnesium indium sulfide (CdIn2S4/MgIn2S4, CMIS) as photoactive material. Specifically, the well-matched energy level structure and narrow energy level gradients between CdIn2S4 and MgIn2S4 could accelerate the separation of electron-hole (e--h+) pairs in the CMIS heterojunction to enhance the photocurrent of CMIS, which was increased 5.5 and 80 times compared with that of single CdIn2S4 and MgIn2S4, respectively. Meanwhile, using CMIS as photoactive material, increasing the biocompatibility by dropping Pt NPs on the surface of CMIS to immobilize the antibody through Pt-N bond. Fe3O4-Ab2, acting as the quencher, competitively consumes electron donors and absorbs light, leading to photocurrent quenching. With the increasing of quencher, the photocurrent decreased. Hence, the developed "signal-off" PEC immunosensor realized the trace detection of NSE within the range from 1.0 fg/mL to 10 ng/mL with a low detection limit of 0.34 fg/mL. This strategy provided a new perspective for establishing ternary metal sulfide heterojunction to construct PEC immunosensor for sensitive detection of disease biomarkers.

Neurological Damage Measured by S-100b and Neuron-Specific Enolase in Patients Treated with Electroconvulsive Therapy.

Electroconvulsive therapy (ECT) is considered one of the most effective treatments for psychiatric disorders. ECT has proven effective in the treatment of depression, mania, catatonia and psychosis. It is presumed that seizures induced during ECT administration cause toxicity and potentially neuronal and glial cell death. A broad range of neurological disorders increase cerebrospinal fluid and serum levels of neuron-specific enolase (NSE) and S-100b protein. This study aims to investigate the effect of ECT on NSE and S-100b levels, which, together, serve as a proxy for neuronal cell damage. Serum concentrations of S-100b and NSE of adult patients who received ECT were measured by immunoluminometric analysis before and after treatment. A two-way ANOVA test was used to estimate the statistical differences in marker concentrations between the subgroups of the study population. Results: A total of 55 patients were included in the analysis: 52.73% (n = 29) were diagnosed with depression, 21.82% (n = 12) with schizophrenia or other psychosis, 16.36% (n = 9) with mania and 9.09% (n = 5) with catatonia. There were no statistically significant changes in NSE (p = 0.288) and S-100b (p = 0.243) levels. We found no evidence that ECT induced neuronal damage based on NSE and S-100b protein levels measured in the serum of patients before and after treatment.

Adrenocorticotropic hormone therapy alters Q-albumin ratios in patients with infantile epileptic spasms syndrome of unknown etiology.

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.

Comparative Analysis of Right vs. Left Radial Access in Percutaneous Coronary Intervention: Impact on Silent Cerebral Ischemia.

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.

Comment on Utsumi et al. Differences in Pathophysiology and Treatment Efficacy Based on Heterogeneous Out-of-Hospital Cardiac Arrest. Medicina 2024, 60, 510.

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.

Utility of melatonin on brain injury, synaptic transmission, and energy metabolism in rats with sepsis.

Melatonin is a powerful endogenous antioxidant hormone. Its healing effects on energy balance and neuronal damage associated with oxidative metabolism disorders have been reported in pathologic conditions. We aimed to determinate the utility of melatonin on neuronal damage, synaptic transmission, and energy balance in the brain tissue of rats with sepsis induced with LPS. Rats was divided into four groups such as control, LPS (20 mg/kg i.p.), melatonin (10 mg/kg i.p. × 3), and LPS + Melatonin (LPS + Mel). After 6 h from the first injection, rats were decapitated, and also tissue and serum samples were taken. Lipid peroxidation and neuron-specific enolase (NSE) levels were determined from the serum in all group. High energy compounds, creatine, and creatine phosphate are measured by HPLC methods from the homogenized tissue. Counts of living neurons are marked with NeuN (neuronal nuclei), degenerated neurons are marked with S100-ß and synaptic vesicles transmission is analyzed with synaptophysin antibodies immunoreactivities. One-way ANOVA and post hoc Tukey tests were used to statistical analysis. In LPS group, AMP, ATP, creatine, and creatine phosphate levels were significantly decreased (p < 0.05), and also ADP levels were significantly increased compared with the other groups (p < 0.01). Living neurons counts were significantly decreased in LPS (p < 0.01), melatonin, and LPS + Melatonin (p < 0.05) groups compared with control. Degenerated neurons counts were increased in LPS group compared with control (p < 0.01) and also decreased in both of melatonin and LPS + Melatonin groups (p < 0.01). Synaptophysin immunoreactivity was decreased in LPS group compared with the other groups (p < 0.05). We observed that melatonin administration prevents neuronal damage, regulates energy metabolism, and protects synaptic vesicle proteins from sepsis-induced reduction.

Performance of the ERC/ESICM-recommendations for neuroprognostication after cardiac arrest: Insights from a prospective multicenter cohort.

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.

Relationships among hemolysis indicators and neuron-specific-enolase in patients undergoing veno-arterial extracorporeal membrane oxygenation.

Neuron-specific-enolase is used as a marker of neurological prognosis after cardiopulmonary resuscitation. It is also present in red blood cells and platelets. It is not known whether hemolysis increases the values of neuron-specific-enolase enough to clinically affect its interpretation in critically ill patients who are to be introduced to veno-arterial extracorporeal oxygenation. In this study, we examined the relationships among neuron-specific-enolase and hemolysis indicators such as free hemoglobin and lactate dehydrogenase after the introduction of veno-arterial extracorporeal oxygenation. Of the 91 patients who underwent veno-arterial extracorporeal membrane oxygenation in our hospital from January 1, 2018, to February 24, 2021, 68 patients survived for more than 24 h. Of these, 14 patients who were categorized into the better cerebral performance categories (1-3) and 19 patients who were categorized into the poor neurological prognosis category (4) were included. After the introduction of veno-arterial extracorporeal membrane oxygenation, neuron-specific-enolase was markedly higher in the poor neurological prognosis group than in the good neurological prognosis group (41.6 vs. 92.0, p = 0.04). A significant positive correlation was revealed between neuron-specific-enolase and free hemoglobin in the good neurological prognosis group (rs = 0.643, p = 0.0131). A similar relationship was observed for lactate dehydrogenase and neuron-specific-enolase in both the conscious (rs = 0.737, p = 0.00263) and non-conscious groups (rs = 0.544, p = 0.0176). When neuron-specific-enolase is used as a marker for neuroprognostic evaluation, an abnormally high value is likely to indicate the lack of consciousness, whereas a lower elevation should be interpreted with caution, taking into account the effects of hemolysis.

Clinical value of serum neuron-specific enolase in sepsis-associated encephalopathy: a systematic review and meta-analysis.

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.

Predictive value of interleukin-6 combined with serum neuron-specific enolase on the prognosis of acute ischemic stroke.

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.

Neuron-Specific Enolase as a Predictor of Neurologic Outcomes in Extracorporeal Cardiopulmonary Resuscitation Patients.

Background: Neuron-specific enolase (NSE) has traditionally been used as a biomarker to predict neurologic outcomes after cardiac arrest. This study aimed to evaluate the utility of NSE in predicting neurologic outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Methods: This observational cohort study included 47 consecutive adult ECPR patients (median age, 59.0 years; 74.5% males) treated between January 2018 and December 2021 at a tertiary extracorporeal life support center. The primary outcome was a poor neurologic outcome, defined as a Cerebral Performance Category score of 3-5 at hospital discharge. Results: Twelve (25.5%) patients had abnormal findings on computed tomography of the brain. A poor neurologic outcome was demonstrated in 22 (46.8%) patients. The NSE level at 72 h after ECPR showed the best prediction power for a poor neurologic outcome compared with NSE at 24 and 48 h. A cutoff value exceeding 61.9 µg/L for NSE at 72 h yielded an area under the curve (AUC) of 0.791 for predicting poor neurologic outcomes and exceeding 62.1 µg/L with an AUC of 0.838 for 30-day mortality. Conclusions: NSE levels at 72 h after ECPR appear to be a reliable biomarker for predicting poor neurologic outcomes and 30-day mortality in ECPR patients.