A prospective observational study on utility of serum mesencephalic astrocyte-derived neurotrophic factor as a promising prognostic biomarker of severe traumatic brain injury in humans.

BACKGROUND: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is released under endoplasmic reticulum stress, thereby exerting neuroprotective effects. We determined whether serum MANF may be a prognostic biomarker of human severe traumatic brain injury (sTBI). METHODS: Serum MANF concentrations of 137 sTBI patients and 137 controls were quantified in this prospective cohort study. Patients with extended Glasgow outcome scale (GOSE) scores of 1-4 at post-traumatic 6 months were considered to have poor prognosis. Relationships between serum MANF concentrations and severity plus prognosis were investigated using multivariate analyses. Area under receiver operating characteristic curve (AUC) was calculated for reflecting prognostic efficiency. RESULTS: As compared to controls, there was a significant increase of serum MANF concentrations after sTBI (median, 18.5 ng/ml versus 3.0 ng/ml; P < 0.001), which was independently correlated with Glasgow coma scale (GCS) scores [ß, -3.000; 95% confidence interval (CI), -4.525--1.476; VIF, 2.216; P = 0.001], Rotterdam computed tomography (CT) scores (ß, 4.020; 95% CI, 1.446-6.593; VIF, 2.234; P = 0.002) and GOSE scores (ß, -0.056; 95% CI, -0.089--0.023; VIF, 1.743; P = 0.011). Serum MANF concentrations substantially distinguished risk of poor prognosis with AUC of 0.795 (95% CI, 0.718-0.859) and its concentrations > 23.9 ng/ml was predictive of poor prognosis with 67.7% sensitivity and 81.9% specificity. Serum MANF concentrations combined with GCS scores and Rotterdam CT scores displayed markedly higher prognostic predictive ability than each of them (all P < 0.05). Using restricted cubic spline, there was a linear correlation between serum MANF concentrations and poor prognosis (P = 0.256). Serum MANF concentrations > 23.9 ng/ml was independently associated with poor prognosis (odds ratio, 2.911; 95% CI, 1.057-8.020; P = 0.039). A nomogram was built, where serum MANF concentrations > 23.9 ng/ml, GCS scores and Rotterdam CT scores were integrated. Hosmer and Lemeshow test, calibration curve and decision curve analysis demonstrated such a prediction model was comparatively stable and was of relatively high clinical benefit. CONCLUSIONS: Substantially increased serum MANF concentrations after sTBI are highly correlated with traumatic severity and are independently predictive of long-term poor prognosis, suggesting that serum MANF may represent a useful prognostic biochemical marker of human sTBI.

Utility of serum nuclear factor erythroid 2-related factor 2 as a potential prognostic biomarker of severe traumatic brain injury in adults: A prospective cohort study.

Objective: Nuclear factor erythroid 2-related factor 2 (Nrf2) may harbor endogenous neuroprotective role. We strived to ascertain the prognostic significance of serum Nrf2 in severe traumatic brain injury (sTBI). Methods: This prospective cohort study included 105 controls and 105 sTBI patients, whose serum Nrf2 levels were quantified. Its relations to traumatic severity and 180-day overall survival, mortality, and poor prognosis (extended Glasgow Outcome Scale score 1-4) were discerned using multivariate analysis. Results: There was a substantial enhancement of serum Nrf1 levels of patients (median, 10.9 vs. 3.3 ng/ml; P < 0.001), as compared to controls. Serum Nrf2 levels were independently correlative to Rotterdam computed tomography (CT) scores (ρ = 0.549, P < 0.001; t = 2.671, P = 0.009) and Glasgow Coma Scale (GCS) scores (ρ = -0.625, P < 0.001; t = -3.821, P < 0.001). Serum Nrf2 levels were significantly higher in non-survivors than in survivors (median, 12.9 vs. 10.3 ng/ml; P < 0.001) and in poor prognosis patients than in good prognosis patients (median, 12.5 vs. 9.4 ng/ml; P < 0.001). Patients with serum Nrf2 levels > median value (10.9 ng/ml) had markedly shorter 180-day overall survival time than the other remainders (mean, 129.3 vs. 161.3 days; P = 0.002). Serum Nrf2 levels were independently predictive of 180-day mortality (odds ratio, 1.361; P = 0.024), overall survival (hazard ratio, 1.214; P = 0.013), and poor prognosis (odds ratio, 1.329; P = 0.023). Serum Nrf2 levels distinguished the risks of 180-day mortality and poor prognosis with areas under receiver operating characteristic curve (AUCs) at 0.768 and 0.793, respectively. Serum Nrf2 levels > 10.3 ng/ml and 10.8 ng/ml discriminated patients at risk of 180-day mortality and poor prognosis with the maximum Youden indices of 0.404 and 0.455, respectively. Serum Nrf2 levels combined with GCS scores and Rotterdam CT scores for death prediction (AUC, 0.897; 95% CI, 0.837-0.957) had significantly higher AUC than GCS scores (P = 0.028), Rotterdam CT scores (P = 0.007), or serum Nrf2 levels (P = 0.006) alone, and the combination for poor outcome prediction (AUC, 0.889; 95% CI, 0.831-0.948) displayed significantly higher AUC than GCS scores (P = 0.035), Rotterdam CT scores (P = 0.006), or serum Nrf2 levels (P = 0.008) alone. Conclusion: Increased serum Nrf2 levels are tightly associated with traumatic severity and prognosis, supporting the considerable prognostic role of serum Nrf2 in sTBI.

Serum Sulfonylurea Receptor-1 Levels After Acute Supratentorial Intracerebral Hemorrhage: Implication for Prognosis.

Objective: Sulfonylurea receptor-1 (SUR1) is implicated in acute brain injury. This study was designed to determine relationship between serum SUR1 levels and severity, early neurologic deterioration (END) plus clinical outcome after intracerebral hemorrhage (ICH). Methods: Serum SUR1 levels of 131 ICH patients and 131 healthy controls were quantified in this prospective, observational study. END was defined as an increase of 4 or more points in the National Institutes of Health Stroke Scale (NIHSS) score or death within 24 hours after admission. Patients with a modified Rankin scale (mRS) score of 3-6 at 90 days following onset were considered to experience a poor outcome. Results: Serum SUR1 levels were substantially higher in patients than in controls. Serum SUR1 levels of patients were highly correlated with NIHSS score, Glasgow Coma Scale score, hematoma volume and ICH score. Compared with patients with END or mRS score of 0-2, other remainders had significantly elevated serum SUR1 levels. Serum SUR1 levels independently predicted END and 90-day poor outcome. Under receiver operating characteristic curve, serum SUR1 levels significantly predicted END and a poor outcome at 90 days after hemorrhagic stroke and its predictive value was similar to those of NIHSS score, Glasgow coma scale score, hematoma volume and ICH score. Conclusion: Serum SUR1 levels are highly correlated with severity, END and poor outcome after hemorrhagic stroke, indicating that serum SUR1 may be useful for risk stratification and prognostic prediction of ICH.

Measuring serum melatonin concentrations to predict clinical outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Oxidative stress has a key role in brain injury and melatonin possesses antioxidant effects. We aimed to ascertain the potential relationship between serum melatonin concentrations and functional outcome following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This prospective and observational study was conducted of 169 aSAH patients. Baseline serum melatonin concentrations were determined. A worse 6-month functional outcome was defined as a Glasgow Outcome Scale score of 1-3. RESULTS: Patients with a worse outcome (56 cases) compared to those with a good outcome (113 cases) exhibited significantly higher concentrations of serum melatonin (P < 0.001). An area under the receiver operating curve of 0.819 was revealed for the prediction of 6-month worse outcome by serum melatonin concentrations. Multiple logistic regression analysis showed an independent association of serum melatonin concentrations with 6-month worse outcome (odds ratio = 1.204). An intimate correlation existed between serum melatonin concentrations and World Federation of Neurological Surgeons subarachnoid hemorrhage scale scores as well as between serum melatonin concentrations and modified Fisher scores (P < 0.001). CONCLUSIONS: Patients with higher serum melatonin concentrations are more likely to have a poor prognosis. Serum melatonin can be considered as an independent predictor of functional outcome after aSAH.