Enolase Levels Research Articles

Effects of age and time since injury on traumatic brain injury blood biomarkers: a TRACK-TBI study.

Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers-plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase-among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17-39 years, middle-aged: 40-64 years, older: 65-90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84-0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6 hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.

Assessment of neuron-specific enolase, glycated haemoglobin and fasting plasma glucose levels in patients with diabetes peripheral neuropathy in Calabar Metropolis, Nigeria: A case control study

Background: Persistent hyperglycemia has been implicated in the development of neuronal complications in diabetes patients. Nerve damage and metabolic abnormalities may cause the release of neuron specific enolase into circulation. Aim: To investigate the relationship between serum neuron-specific enolase (NSE), fasting plasma glucose (FPG) and glycated haemoglobin (HbA1C) levels in diabetic patients with peripheral neuropathy. Methods: one hundred and five patients with peripheral neuropathy and 60 apparently healthy non-diabetic controls aged 45-69 years attending Clinics in General Hospital Calabar and the University of Calabar Teaching Hospital, Calabar, between July 2021 and January 2022, were recruited into the study. Fasting plasma glucose was estimated using glucose oxidase peroxidase method. Glycated haemoglobin and NSE were determined using Boronate Affinity High Performance Liquid Chromatography and ELISA methods respectively. Height and weight were measured and BMI computed, and data analyzed using Student’s t-test, ANOVA, post hoc analysis and Pearson’s correlation at P<0.05. Results: Body mass index, blood pressure, fasting plasma glucose, glycated haemoglobin and neuron specific enolase concentrations were significantly different (P=<0.05) between the diabetic patients and the controls. Neuron specific enolase vary significantly (P<0.05) among the diabetic patients with different forms of diabetes peripheral neuropathy. Fasting plasma glucose correlated positively with NSE (r=0.441, P=0.000) and HbA1C (r=0.328, P=0.001) respectively. Glycated haemoglobin correlated positively with BMI (r=0.412, P=0.000) and NSE (r=0.328, P=0.001) in that order. Conclusion: This study has shown that glycated haemoglobin and fasting plasma glucose are related with neuron specific enolase levels in patients with diabetes peripheral neuropathy. Thus, rising levels of glycated haemoglobin and fasting plasma glucose (poor glycemic control) may be associated with progressive nerve damage in patients with diabetes peripheral neuropathy.

Effects of Aerobic Exercise on Markers of Brain Injury in Methamphetamine-Dependent Individuals: A Randomized Controlled Trial.

Drug dependence has become a major global public health problem. This study aimed to investigate the effects of moderate-intensity aerobic exercise on the blood-brain barrier and neurological damage in methamphetamine (MA)-dependent individuals. MA-dependent individuals (all males) were recruited and randomly divided into MA exercise group (MAE) and MA control group (MAC) by using random number table method. The MAE group underwent 12 weeks of moderate-intensity aerobic exercise, and the MAC group underwent conventional detoxification. The Neurofilament light chain (NfL), S100 calcium binding protein b (S100b), and Neuron-Specific Enolase (NSE) levels in the blood of MA-dependent individuals were measured before and after the exercise intervention. After the exercise intervention was implemented, the amount of change in NfL in the plasma of the MAE (1.75 ± 1.40) group was significantly different from that of the MAC (0.60 ± 1.21) group (p < 0.01); the amount of change in NSE in the serum of the MAE [-1.51 (-3.99~0.31)] group was significantly different from that of the MAC [0.03 (-1.18~1.16)] group (p < 0.05); and the amount of change in S100b in the serum of the MAE [0.66 (0.40~0.95)] group was not significantly different from that of the MAC (0.60 (0.21~1.04)) group (p > 0.05). This study showed that 12 weeks of moderate-intensity aerobic exercise treatment significantly promoted the recovery of blood-brain barrier and neurological damage in MA-dependent patients compared with conventional withdrawal.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Neurological symptoms and neuronal damage markers in acute COVID-19: Is there a correlation? A pilot study.

A wide spectrum of neurological symptoms (NS) has been described in patients with COVID-19. We examined the plasma levels of neuron-specific enolase (NSE) and neurofilament light chain (NFL) together, as neuronal damage markers, and their relationships with clinical severity in patients with NS at acute COVID-19.A total of 20 healthy controls and 59 patients with confirmed COVID-19 were enrolled in this pilot prospective study. Serum NSE and NFL levels were measured by using the enzyme-linked immunoassay method from serum samples.Serum NSE levels were found to be significantly higher in the severe group than in the nonsevere group (p = 0.034). However, serum NFL levels were similar between the control and disease groups (p > 0.05). For the mild group, serum NFL levels were significantly higher in patients with the sampling time ≥5 days than in those with the sampling time <5 days (p = 0.019). However, no significant results for NSE and NFL were obtained in patients with either single or multiple NS across the groups (p > 0.05).Increased serum NSE levels were associated with disease severity regardless of accompanied NS in patients with acute COVID-19 infection. However, serum NFL levels may have a role at the subacute phase of COVID-19.

Are Interictal Discharges Associated with Neuronal Cell Loss in Electrical Status Epilepticus in Sleep?

Neuron-specific enolase is an established biomarker of neuronal damage. This study aimed to reveal the relationship between serum neuron-specific enolase level and continuous interictal discharges in a group of encephalopathy with electrical status epilepticus in sleep patients for the first time and determine whether there is a neuronal cell loss or damage. We analyzed serum neuron-specific enolase levels in patients with an electrical status epilepticus in sleep pattern on their electroencephalographs with age- and sex-matched control subjects. Patients with a spike-wave index of at least 50% and acquired neuropsychological regression were included in the study. Magnetic resonance imaging of all electrical status epilepticus in sleep patients and control subjects included in the study was within normal limits. Neuron-specific enolase is measured by the enzyme-linked immunosorbent assay kit based on the sandwich technique. In this study, 14 patients diagnosed with electrical status epilepticus in sleep and 21 healthy controls were included. The median age of electrical status epilepticus in sleep patients was 7.1 years (min-max: 4.5-10.7 years) and 7.7 years (min-max: 3.2-14 years) in the control subjects. According to the results of serum neuron-specific enolase measurements, the mean ± standard deviation level of neuron-specific enolase was 7.61 ± 3.19 ng/dL for the electrical status epilepticus in sleep group and 6.93 ± 2.55 ng/dL for the control group. Serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and the control group were not statistically significant (P = .749). No significant difference was observed in serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and control subjects. Our results may indicate that frequent interictal discharges do not result in neuronal cell loss or damage in electrical status epilepticus in sleep patients.

Neuroprotection role of cooling helmet on neuron specific enolase (NSE) and post-surgery delirium levels in open heart surgery patients: a randomized controlled trial

Background &amp; objective: This study aims to assess the effect of cooling helmet during surgery on neuron specific enolase (NSE) and delirium levels following open heart surgery patients with cardiopulmonary bypass (CPB) using a heart-lung machine.&#x0D; Methodology: This double-blind randomized clinical trial took place from October to December 2021 in a tertiary care hospital. The research used a modified cooling helmet to decrease brain temperature. Inclusion criteria were adult patients who were scheduled for open heart surgery with CPB. The subjects were randomized into two groups: patients with the cooling helmet on as the treatment group (n = 12) and the patients with the non-cooling helmet on as the control group (n = 13). The differences between NSE and delirium levels in both groups were assessed at specific times.&#x0D; Results: NSE levels in the treatment group were lower than the control group (7.13 ± 7.63 vs. 12.49 ± 6.81; P &lt; 0.05). Regarding the delirium, no statistically significant difference was found in both groups (P &gt; 0.05).&#x0D; Conclusion: The hypothermia effect of the cooling helmet is associated with a decrease of neuron specific enolase levels, but it did not significantly correlate to prevent the delirium after open heart surgery patients with the cardiopulmonary bypass machine.&#x0D; Abbreviations: CABG: coronary artery bypass graft; CPB: Cardiopulmonary Bypass; CMRO2: cerebral metabolic rate of oxygen; HLM: Heart-lung machine; NSE: Neuron Specific Enolase; ROS: reactive oxygen species&#x0D; Citation: Adji MP, Hidayat JK, Heriwardito A. Neuroprotection role of cooling helmet on neuron specific enolase (NSE) and post-surgery delirium levels in open heart surgery patients: a randomized controlled trial. Anaesth. pain intensive care 2022;26(5):588-594; DOI: 10.35975/apic.v26i5.1985

Effects of Supplemental Dexmedetomidine Anesthesia on Intracranial Aneurysm Patients Undergoing Intracranial Interventional Embolization

Intracranial aneurysm (IA) has been identified in approximately 0.4%-3% of the population and associated with 3%-10% mortality. IA is the major factor attributing to spontaneous subarachnoid hemorrhage. We aim to investigate that whether employing dexmedetomidine (DEX), an α2 adrenergic receptor agonist, as a supplementation could impact the outcomes of patients with intracranial interventional embolization. Patients were randomly divided into a control group (n= 48 cases) and a DEX (0.6 μg/kg) supplement group (n= 48 cases). Patients' outcomes were evaluated using the Glasgow Outcome Scale. Serum levels of norepinephrine, cortisol, interleukin-6, C-reactive protein, neuron-specific enolase, and S100β were determined using enzyme-linked immunoassay. The cognitive function of patients was assessed using the Mini-Mental State Exam and Montreal Cognitive Assessment tests. DEX supplementation during anesthesia reduced adverse reaction, surgical stress, and attenuated cognitive impairment after extubation in IA patients' postintracranial interventional embolization. Our study demonstrated that employing DEX as supplementation during anesthesia could effectively reduce surgical stress and improve cognitive function, ultimately improving patients' recovery from intracranial interventional embolization.

Prevention of Dexmedetomidine on Postoperative Delirium and Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Thoracoscopic Lobectomy.

Objective To investigate the effect of dexmedetomidine on postoperative cognitive function and delirium in elderly patients undergoing thoracoscopic lobectomy. Methods 109 elderly patients (age is more than 65 years) who underwent thoracoscopic lobectomy in our hospital from June 2020 to Feb 2022 were randomly divided into the dexmedetomidine (DEX) group (n = 54) and the control group (n = 55). The patients in the experimental group were given dexmedetomidine by intravenous pump, intravenous pump 0.5 μg/kg within 10 minutes, and maintained the speed of 0.5 μg/(kg. h) to 30 min before the operation was ended. The control group was given the same amount of normal saline. Delirium assessment-severity (CAM-S) assessment and Mini-Cog were used to assess the severity levels of POD and POCD 24 h before, 6 hours after, one day after the operation, three days after the operation, and 1 week after the operation. Serum TNF-αα and NSE levels were assessed by using enzyme-linked immunosorbent assay. NRS pain marks were assessed in the DEX group at postanesthesia care unit (PACU) and 24 postoperation. Surgical pierhysmographic index (SPI) evaluation was performed at five time points. Results The Mini-Cog scores in the DEX group were markedly enhanced compared with those in the saline group 6 and 24 hours after the operation. The SPI values in the DEX group were markedly reduced within 2 min after intubation and at surgical sutures. Moreover, the CAM scores in the DEX group were markedly reduced 24 hours after the operation. Tumor necrosis factor-α (TNF-α) and neuron-specific enolase (NSE) levels were significantly decreased in the DEX group at T1∼T3. Conclusion The use of dexmedetomidine in the thoracoscopic lobectomy in elderly patients could reduce the occurrence and severity of postoperative cognitive dysfunction and delirium.

A retrospective study of the correlation between herpes zoster neuralgia and the serum neuron-specific enolase level in the largest dermatological hospital in Zhejiang province, China.

We studied the changes and clinical significance of the serum neuron-specific enolase (NSE) level in peripheral blood of patients with post-herpetic neuralgia (PHN).Material and methodsPatients with PHN were divided into a mild PHN group and a severe PHN group according to their scores on a 100-point Likert scale representing the degree of neuralgia. NSE levels in neuralgia patients and healthy volunteers were then compared by t-test. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic efficiency of NSE for PHN. The correlation between NSE level and Likert scale score after treatment was analyzed.ResultsNSE levels in PHN patients were higher than those in the healthy volunteers. Patients in the severe PHN group had higher NSE levels than those in the mild PHN group. NSE level at admission was associated with the Likert scale score recorded on the 14th day of treatment (136.1 ± 32.81 vs. 87.53 ± 16.23 pg/mL) (P < 0.05). The ROC curve of NSE levels for PHN is shown that the area was 0.8713 (95% confidence interval, 0.7861–0.9564; p < 0.0001).ConclusionsThere was a correlation between NSE and PHN, in that the NSE level positively correlated with the short-term prognosis of patients with PHN.

Hiponatremili hastalarda serum nöron spesifik enolaz düzeyleri ile beyin hasarı arasındaki ilişki

Purpose: In this study, we aimed to investigate the effects of serum neuron specific enolase on the prediction of central nervous system injury and the clinical course in patients to have hyponatremia.&#x0D; Materials and Methods: 75 adult patients with serum sodium levels less than 135 mEq/L were evaluated. The patients were grouped according to serum neuron specific enolase levels (group 1 ≤ 17.0 ng/mL and group 2 &gt; 17.0 ng/mL). The groups were compared according to demographic and laboratory data. &#x0D; Results: The incidence of hypertension, heart failure, and loss of consciousness was significantly higher in group 2 patient. High neuron specific enolase levels were related to lower serum sodium levels. The mean sodium levels were 129.5 ± 4.3 mEq/L and 126 ± 4.5 mEq/L in groups 1 and 2, respectively. Of the patients in group 2 (n = 45), 8 patients with loss of consciousness (low Glasgow Coma Scale scores) (i.e.

Clinical efficacy of combined use of Xuebijing and mild hypothermia therapy for the treatment of severe traumatic brain injury, and its effect on patient mortality and complications

Purpose: To investigate the clinical efficacy of combined use of Xuebijing and mild hypothermia therapy in severe traumatic brain injury (TBI), and its effect on mortality and incidence of complications.&#x0D; Methods: Eighty-six severe TBI patients admitted to The Fourth People's Hospital of Chongqing were selected. Patients were randomly and equally assigned to control group (COG) who received conventional treatment, and study group (EXG) given a combination of Xuebijing and mild hypothermia therapy. Relevant clinical indicators and therapeutic effects were compared.&#x0D; Results: Post-treatment levels of inflammatory indices, including procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly reduced, with lower levels in EXG (p &lt; 0.05). Between-group differences were seen in human leukocyte antigen-DR isotype (HLA-DR), CD3+, CD4+, CD8+, and C3 indicators (p &lt; 0.05). EXG had significantly lower protein expression levels of neuron-specific enolase (NSE) and S100 beta than COG (p &lt; 0.05). After treatment, plasma protein levels of coagulation indices, viz, prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower than pre-treatment levels, with even much lower levels in EXG (p &lt; 0.05). There were reduced incidence of lung infection, acute gastrointestinal injury, acute respiratory distress syndrome (ARDS) and hypernatremia (p &lt; 0.05). More patients had better recovery in EXG (p &lt; 0.05) than in control group.&#x0D; Conclusion: The combined therapy improves the prognosis of severe TBI, lowers the levels of inflammatory factors, ameliorates plasma coagulation, and enhances immunity with a high degree of safety. However, further clinical trials should be undertaken prior to application in clinical practice

Regional Cerebral Oxygenation in Patients with Severe COVID-19

The aim of the study was to assess regional cerebral oxygenation (rScO₂) in patients with acute respiratory distress syndrome (ARDS) associated with COVID-19.Material and methods. The cross-sectional study was conducted. Twenty-eight patients with severe COVID-19 who were admitted in the intensive care unit were enrolled. Regional cerebral oxygenation was assessed using near-infrared spectroscopy, laboratory markers of cerebral damage, clinical and laboratory characteristics.Results. Median age of patients was 65 years, of whom 50% were men. Three (11%) patients had severeARDS, 8 (29%) patients had moderate ARDS, and 17 (60%) patients had mild ARDS. Mechanical ventilation was performed in 20 (71%) patients, vasopressors were used in 14 (50%) patients. The median levels of cerebral saturation were normal and did not differ between the left (rScO₂l) and right (rScO₂r) hemispheres (68 (58–75) and 69 (59–76), respectively). The level of S-100 protein was increased (0.133 (0.061–0.318) µg/l) in contrast to the normal level of neuron-specific enolase (12.5 (8.0–16.5) µg/l). A correlation was found only between rScO₂ and hemoglobin level (rho=0.437, P=0.02) and between rScO₂ and lymphocyte count (rho=–0.449, P=0.016). An increase in S-100 negatively correlated with a decrease in Glasgow Coma Scale score (rho=–0.478, P=0.028).Conclusion. Near-infrared spectroscopy did not reveal a decrease in rScO₂ among patients with ARDS associated with COVID-19. The S-100 protein is a useful marker for the assessment of impaired consciousness. Further study of the causes of cerebral dysfunction in patients with severe COVID-19 and methods for its early identification is warranted.

Are Interictal Discharges Associated with Neuronal Cell Loss in Electrical Status Epilepticus in Sleep?

Neuron-specific enolase is an established biomarker of neuronal damage. This study aimed to reveal the relationship between serum neuron-specific enolase level and continuous interictal discharges in a group of encephalopathy with electrical status epilepticus in sleep patients for the first time and determine whether there is a neuronal cell loss or damage. We analyzed serum neuron-specific enolase levels in patients with an electrical status epilepticus in sleep pattern on their electroencephalographs with age- and sex-matched control subjects. Patients with a spike-wave index of at least 50% and acquired neuropsychological regression were included in the study. Magnetic resonance imaging of all electrical status epilepticus in sleep patients and control subjects included in the study was within normal limits. Neuron-specific enolase is measured by the enzyme-linked immunosorbent assay kit based on the sandwich technique. In this study, 14 patients diagnosed with electrical status epilepticus in sleep and 21 healthy controls were included. The median age of electrical status epilepticus in sleep patients was 7.1 years (min-max: 4.5-10.7 years) and 7.7 years (min-max: 3.2-14 years) in the control subjects. According to the results of serum neuron-specific enolase measurements, the mean ± standard deviation level of neuron-specific enolase was 7.61 ± 3.19 ng/dL for the electrical status epilepticus in sleep group and 6.93 ± 2.55 ng/dL for the control group. Serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and the control group were not statistically significant (P = .749). No significant difference was observed in serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and control subjects. Our results may indicate that frequent interictal discharges do not result in neuronal cell loss or damage in electrical status epilepticus in sleep patients.

From tumor mutational burden to characteristic targets analysis: Identifying the predictive biomarkers and natural product interventions in cancer management.

High-throughput next-generation sequencing (NGS) provides insights into genome-wide mutations and can be used to identify biomarkers for the prediction of immune and targeted responses. A deeper understanding of the molecular biological significance of genetic variation and effective interventions is required and ultimately needs to be associated with clinical benefits. We conducted a retrospective observational study of patients in two cancer cohorts who underwent NGS in a “real-world” setting. The association between differences in tumor mutational burden (TMB) and clinical presentation was evaluated. We aimed to identify several key mutation targets and describe their biological characteristics and potential clinical value. A pan-cancer dataset was downloaded as a verification set for further analysis and summary. Natural product screening for the targeted intervention of key markers was also achieved. The majority of tumor patients were younger adult males with advanced cancer. The gene identified with the highest mutation rate was TP53, followed by PIK3CA, EGFR, and LRP1B. The association of TMB (0–103.7 muts/Mb) with various clinical subgroups was determined. More frequent mutations, such as in LRP1B, as well as higher levels of ferritin and neuron-specific enolase, led to higher TMB levels. Further analysis of the key targets, LRP1B and APC, was performed, and mutations in LRP1B led to better immune benefits compared to APC. APC, one of the most frequently mutated genes in gastrointestinal tumors, was further investigated, and the potential interventions by cochinchinone B and rottlerin were clarified. In summary, based on the analysis of the characteristics of gene mutations in the “real world,” we obtained the potential association indicators of TMB, found the key signatures LRP1B and APC, and further described their biological significance and potential interventions.

Potential factors of cytokeratin fragment 21-1 and cancer embryonic antigen for mediastinal lymph node metastasis in lung cancer.

Objective: Lung cancer is a common malignant tumor, characterized by being difficult to detect and lacking specific clinical manifestations. This study aimed to find out the risk factors of mediastinal lymph node metastasis and explore the correlation between serum tumor markers and mediastinal lymph node metastasis and lung cancer prognosis. Methods: A retrospective study of 3,042 lung cancer patients (330 patients with mediastinal lymph node metastasis and 2,712 patients without mediastinal lymph node metastasis) collected from the First Affiliated Hospital of Nanchang University from April 1999 to July 2020. The patients were divided into two groups, namely, mediastinal lymph node metastasis group and non-mediastinal lymph node metastasis group. Student’s t test, non-parametric rank sum test and chi-square test were used to describe whether there is a significant difference between the two groups. We compared the serum biomarkers of the two groups of patients, including exploring serum alkaline phosphatase (ALP), calcium hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA-199, CA -153, cytokeratin fragment 19 (CYFRA 21-1), total prostate specific antigen (TPSA), neuron-specific enolase (NSE) levels and the incidence and prognosis of lung cancer mediastinal lymph node metastasis. Binary logistic regression analysis was used to determine its risk factors, and receiver operating curve (ROC) analysis was used to evaluate its diagnostic value for mediastinal lymph node metastasis. Results: Binary logistic regression analysis showed that carcinoembryonic antigen and CYFRA 21-1 were independent risk factors for mediastinal lymph node metastasis in patients with lung cancer (p < 0.001 and p = 0.002, respectively). The sensitivity and specificity of CEA for the diagnosis of mediastinal lymph node metastasis were 90.2 and 7.6%, respectively; CYFRA 21-1 were 0.6 and 99.0%, respectively. Conclusion: Serum CEA and CYFRA 21-1 have predictive value in the diagnosis of mediastinal lymph node metastasis in patients with lung cancer.

CEACAM6 serves as a biomarker for leptomeningeal metastasis in lung adenocarcinoma.

Diagnosis of leptomeningeal metastasis (LM) is challenging. In our previous study, CEACAM6 mRNA was found to be highly expressed in the circulating tumor cells of cerebrospinal fluid (CSF) from patients with lung adenocarcinoma with LM (LUAD-LM). The aim of this study was to identify whether CEACAM6 could be used as a biomarker for LUAD-LM. The level of CEACAM6 was determined by enzyme-linked immunosorbent assay (ELISA) in CSF from 40 LUAD-LM and 44 normal controls, and additional serum samples from 138 LUAD patients, including 12 LUAD-LM patients, and 30 healthy controls. Carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and neuron-specific enolase (NSE) levels in the CSF and sera were detected by chemiluminescent immunoassay. Receiver operating characteristic curve was plotted to evaluate the diagnostic performance for LUAD-LM. CSF CEACAM6 level was higher in LUAD-LM than that in normal controls. In serum, LUAD patients had a higher level of CAECAM6 than healthy controls, and LM patients had the highest level among them. Serum CEACAM6 had a higher AUC than CEA in differentiating LM from non-LM in LUAD patients (0.95 vs. 0.64, p < 0.001). CEACAM6 may serve as a potential biomarker in diagnosing LUAD-LM.

The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury.

BackgroundModerate to severe traumatic brain injury (TBI) is frequently accompanied by diffuse axonal injury (DAI). Considering the low sensitivity of computed tomography (CT) examination for microbleeds and axonal damage, identification of DAI is difficult using conventional diagnostic methods in the acute phase. Neuron-specific enolase (NSE) has been demonstrated to be increased in serum following various types of TBI and is already clinically/commercially available. We conjecture that serum NSE level to admission GCS score ratio (NGR) may be a useful indicator for the early diagnosis of DAI.MethodsThis study included 115 patients with moderate-to-severe TBI who underwent NSE measurements within 6 h after injury and brain magnetic resonance imaging (MRI) within 30 days. The positive and negative DAI groups were divided according to MRI findings.ResultsAmong the 115 patients, 49 (42.6%) were classified into the DAI group and 66 (57.4%) patients into the non-DAI group by clinical MRI. The NGR of patients without DAI was found to be significantly lower than those of patients with DAI (p < 0.0001). NGR presented the largest Pearson r value (r = 0.755, 95% CI 0.664–0.824, p < 0.0001) and high diagnostic accuracy for DAI [area under the curve (AUC) = 0.9493; sensitivity, 90.91%; and specificity, 85.71%]. Patients with TBI presenting with higher NGR were more likely to suffer an unfavorable neurological outcome [6-month extended Glasgow Outcome Scale (GOSE) 1–4].ConclusionsThe NGR on admission could serve as an independent predictor of DAI with moderate-to-severe TBI.

Oxygen Targets in Comatose Survivors of Cardiac Arrest

BackgroundThe appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown.MethodsIn this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days.ResultsA total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P=0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 μg per liter in the restrictive-target group and 18 μg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups.ConclusionsTargeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.)

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest

BackgroundEvidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited.MethodsIn a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months.ResultsA total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P=0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups.ConclusionsTargeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.)