Elevated serum nuclear factor erythroid 2-related factor 2 levels contribute to a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective cohort study.

Objective: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional factor for antioxidant response element-regulated genes. The purpose of this study was to assess the prognostic role of serum Nrf2 in intracerebral hemorrhage (ICH). Materials and methods: In this prospective observational study, serum Nrf2 levels of 115 acute supratentorial ICH patients and 115 controls were gaged. Early neurologic deterioration (END) was defined as an increase of four or greater points in National Institutes of Health Stroke Scale (NIHSS) score or death at post-stroke 24 h. A poor outcome was referred to as the post-stroke 90-day modified Rankin scale (mRS) score of 3-6. END and a poor outcome were considered as the two prognostic parameters. Results: As compared to controls, serum Nrf2 levels of patients were substantially elevated (P < 0.001), with its levels increasing during the 6-h period immediately, peaking in 12-18 h, plateauing at 18-24 h, and decreasing gradually thereafter (P < 0.05). Serum Nrf2 levels of patients were independently correlated with NIHSS score (t = 3.033; P = 0.003) and hematoma volume (t = 3.210; P = 0.002), independently predicted END (odds ratio 1.125; 95% confidence interval 1.027-1.232; P = 0.011) and poor outcome (odds ratio 1.217; 95% confidence interval 1.067-1.387; P = 0.013), as well as efficiently distinguished END (area under curve 0.771; 95% confidence interval 0.666-0.877; P < 0.001) and poor outcome (area under curve 0.803; 95% confidence interval 0.725-0.882; P < 0.001). Its predictive ability was equivalent to those of NIHSS score and hematoma volume (both P > 0.05), and it also significantly improved their predictive abilities under receiver operating characteristic (ROC) curve (all P < 0.05). Conclusion: Elevated serum Nrf2 levels are closely correlated with severity, END, and 90-day poor outcome following ICH. Hence, Nrf2 may play an important role in acute brain injury after ICH, and serum Nrf2 may have the potential to serve as a prognostic biomarker of ICH.

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.

Usability of serum annexin A7 as a biochemical marker of poor outcome and early neurological deterioration after acute primary intracerebral hemorrhage: A prospective cohort study.

Objective: Annexin A7 (ANXA7), a calcium-dependent phospholipid-binding protein, may act to aggravate brain injury. This study aimed to assess the clinical utility of serum ANXA7 as a predictor of severity, early neurological deterioration (END), and prognosis after intracerebral hemorrhage (ICH). Methods: A total of 126 ICH patients and 126 healthy controls were enrolled. Symptomatic severity was evaluated utilizing the National Institutes of Health Stroke Scale (NIHSS) score. The lesion volume of ICH was measured according to the ABC/2 method. END was referred to as an increase of 4 or greater points in the NIHSS score or death at post-stroke 24 h. The unfavorable functional outcome was a combination of death and major disability at post-stroke 90 days. Results: Serum ANXA7 levels were significantly higher in patients than in controls (median, 46.5 vs. 9.7 ng/ml; P < 0.001). Serum ANXA7 levels were independently correlated with NIHSS score [beta: 0.821; 95% confidence interval (CI): 0.106-1.514; variance inflation factor: 5.180; t = 2.573; P = 0.014] and hematoma volume (beta: 0.794; 95% CI: 0.418-1.173; variance inflation factor: 5.281; t = 2.781; P = 0.007). Serum ANXA7 levels were significantly elevated with increase in modified Rankin scale scores (P < 0.001). Also, serum ANXA7, which was identified as a categorical variable, independently predicted END and an unfavorable outcome with odds ratio values of 3.958 (95% CI: 1.290-12.143; P = 0.016) and 2.755 (95% CI: 1.051-7.220; P = 0.039), respectively. Moreover, serum ANXA7 levels efficiently differentiated END (area under the curve: 0.781; 95% CI: 0.698-0.849) and an unfavorable outcome (area under the curve: 0.776; 95% CI: 0.693-0.846). Conclusion: Serum ANXA7 may represent a useful blood-derived biomarker for assessing the severity, END, and prognosis of ICH.

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.

Predictive value of serum visinin-like protein-1 for early neurologic deterioration and three-month clinical outcome in acute primary basal ganglia hemorrhage: A prospective and observational study.

BACKGROUND: Visinin-like protein 1 (VILIP-1) appears as a biomarker of neuronal injury. We investigated the correlation of serum VILIP-1 concentrations with severity, early neurologic deterioration (END) and functional outcome of intracerebral hemorrhage (ICH). METHODS: In this prospective and observational study, serum VILIP-1 concentrations were quantified in 106 patients with basal ganglia hemorrhage. Univariate and multivariable logistic regression analyses were used to analyze the relationship between serum VILIP-1 concentrations and END plus worse prognosis (modified Rankin Scale score of 3 or greater) at post-injury 3 months. RESULTS: Serum VILIP-1 concentrations of patients were closely correlated with hematoma volume and National Institutes of Health Stroke Scale score. Serum VILIP-1 concentrations were substantially elevated in patients with END or worse 3-month prognosis, as compared to other remainders. Also, serum VILIP-1 concentrations were independently associated with END and worse 3-month prognosis. Under ROC curve analysis, serum VILIP-1 concentrations exhibited marked accuracy for distinguishing patients with the development of END or worse 3-month prognosis. Its predictive ability was in the range of hematoma volume and National Institutes of Health Stroke Scale score. CONCLUSIONS: Serum VILIP-1 may be a good biomarker for assessing hemorrhagic severity and clinical outcomes after ICH.

Elevated Serum Complement C1q Levels After Traumatic Brain Injury and Its Association with Poor Prognosis.

OBJECTIVE: Complement C1q is implicated in neuroinflammation. We intended to discern the relationship between serum C1q levels and severity in addition to prognosis following traumatic brain injury (TBI). METHODS: In this prospective, observational study, serum C1q levels were quantified in 188 TBI patients and 188 healthy controls. Glasgow coma scale (GCS) and Rotterdam computed tomography (CT) classification were used as clinical and radiological indicators of severity. Patients with extended Glasgow outcome scale (GOSE) score of 1-4 at 6 months after trauma were considered to have a poor outcome. Multiple logistic regression model was built to ascertain the independent association of serum C1q levels with 6-month poor outcome. Receiver operating characteristic (ROC) curve was configured for analysis of prognostic capability with respect to serum C1q levels. RESULTS: TBI patients exhibited substantially higher serum C1q levels than controls (median, 223.9 mg/l versus 75.4 mg/l). Serum C1q levels of patients were tightly correlated with GCS score (r = -0.671), Rotterdam CT classification (r = 0.604) and GOSE score (r = -0.581). An area under the ROC curve was yielded of 0.793 (95% confidence interval = 0.728-0.849), and serum C1q levels above 345.5 mg/l discriminated the risk of 6-month poor outcome with 59.6% sensitivity and 92.6% specificity. Serum C1q levels above 345.5 mg/l retained as an independent predictor for 6-month poor outcome with odds ratio of 4.922 (95% confidence interval = 1.552-15.606; P = 0.017). CONCLUSION: Elevated serum C1q levels are closely correlated with traumatic severity and independently predicted the risk of long-term poor prognosis after TBI.

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.

Thyroid function of twin-pregnant women in early pregnancy / 中华医学杂志(英文版)

Background@#Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies.@*Methods@#Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018; 160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies.@*Results@#First-trimester reference ranges (4–12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01–3.35) mIU/L and FT4 16.38 (12.45–23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z = -1.964, P = 0.049); FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z = -6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z = -7.399, P = 0.000) in twin pregnancies in the first trimester.@*Conclusions@#Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.

Thyroid function of twin-pregnant women in early pregnancy / 中华医学杂志(英文版)

BACKGROUND@#Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies.@*METHODS@#Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018; 160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies.@*RESULTS@#First-trimester reference ranges (4-12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01-3.35) mIU/L and FT4 16.38 (12.45-23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z = -1.964, P = 0.049); FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z = -6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z = -7.399, P = 0.000) in twin pregnancies in the first trimester.@*CONCLUSIONS@#Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.

Role of galectin-3 in plasma as a predictive biomarker of outcome after acute intracerebral hemorrhage.

OBJECTIVE: Inflammation is involved in pathophysiological mechanisms underlying secondary brain injury after intracerebral hemorrhage. Enhanced circulating levels of galectin-3, a proinflammatory cytokine, have close relation to poor prognosis of some inflammatory illnesses. This study was designed to investigate whether plasma galectin-3 levels are related to the inflammation, severity and prognosis following intracerebral hemorrhage. METHODS: In this observational, prospective study, plasma galectin-3 levels of 110 patients and 110 controls were determined. We further assessed the association of galectin-3 levels with inflammation reflected by systemic C-reactive protein levels, severity indicated by hematoma volumes and National Institutes of Health Stroke Scale (NIHSS) scores, and endpoints including 1-week mortality, 6-month mortality, 6-month overall survival and 6-month unfavorable outcome (modified Rankin Scale score>2). RESULTS: Plasma galectin-3 levels of patients were significantly higher than those of controls. Galectin-3 was identified as an independent prognostic predictor for 1-week mortality, 6-month mortality, 6-month overall survival and 6-month unfavorable outcome, as well as had strong relation to C-reactive protein levels, hematoma volumes and NIHSS scores. Compared with NIHSS scores and hematoma volumes, plasma galectin-3 levels had similar areas under receiver operating characteristic curve (AUC). Moreover, galectin-3 levels significantly improved AUCs of NIHSS scores or hematoma volumes alone for prediction of 6-month mortality and 6-month unfavorable outcome. CONCLUSIONS: Elevated plasma galectin-3 levels are strongly associated with the inflammation, severity and poor prognosis after intracerebral hemorrhage, indicating galectin-3, involved in brain inflammation, might have the potential to be a prognostic biomarker for hemorrhagic stroke.

Leptin as a marker for severity and prognosis of aneurysmal subarachnoid hemorrhage.

Leptin has been identified as a plasma marker for outcomes in traumatic brain injury and intracerebral hemorrhage. We further investigated whether leptin might serve as a marker for severity and prognosis in aneurysmal subarachnoid hemorrhage. One hundred and eight consecutive patients and 108 sex and age - matched healthy subjects were recruited. Plasma leptin levels were measured by enzyme-linked immunosorbent assay. Clinical severity was assessed using World Federation of Neurological Surgeons score and Fisher score. Mortality and poor long-term outcome (Glasgow outcome scale scores of 1-3) at 6 months were recorded. Plasma leptin levels on admission were substantially higher in patients than in healthy controls, and were significantly associated with the clinical severity. There was also a significant association between leptin levels and clinical outcomes at 6 months in multivariate logistic regression analysis. Using receiver operating characteristic curves, we calculated areas under the curve for clinical outcomes at 6 months. The predictive performance of leptin was similar to, but did not obviously improve those of World Federation of Neurological Surgeons score and Fisher score. Thus, leptin may indicate clinical severity of the initial bleeding and also have prognostic value for clinical outcomes in aneurysmal subarachnoid hemorrhage and may therefore help in guiding treatment decisions in the setting of aneurysmal subarachnoid hemorrhage.

Prognostic value of copeptin: one-year outcome in patients with traumatic brain injury.

High plasma copeptin level has been associated with one-month mortality after traumatic brain injury. However, not much is known regarding its relation with long-term outcome. Thus, we investigated the ability of copeptin to predict 1-year outcome in patients with traumatic brain injury. One hundred and six healthy controls and 106 patients with acute severe traumatic brain injury were included. Plasma samples were obtained on admission. Its concentration was measured by enzyme-linked immunosorbent assay. Forty-eight patients (45.3%) suffered from unfavorable outcome (Glasgow Outcome Scale score of 1-3) and 31 patients (29.2%) died in 1 year after traumatic brain injury. Upon admission, plasma copeptin level in patients was substantially higher than that in healthy controls. A forward stepwise logistic regression selected plasma copeptin level as an independent predictor for 1-year unfavorable outcome and mortality of patients. A receiver operating characteristic curve analysis showed plasma copeptin level predicted 1-year unfavorable outcome and mortality obviously. The predictive value of the copeptin concentration was thus similar to that of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year. In a combined logistic-regression model, copeptin improved the area under curve of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year, but the differences were not significant. Thus, copeptin level is a useful, complementary tool to predict functional outcome and mortality 1 year after traumatic brain injury.