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Background: Interleukin-33 is recently identified as a brain injury biomarker. We determined whether serum interlerukin-33 concentrations are associated with inflammation, severity and prognosis after traumatic brain injury (TBI)., Methods: We detected serum interlerukin-33 concentrations of 102 healthy controls and 102 severe TBI patients, as well as serum concentrations of 3 inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha and C-reactive protein) and 7 cell-specific proteins (myelin basic protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase, phosphorylated axonal neurofilament subunit H, Tau and ubiquitin carboxyl-terminal hydrolase L1) in 102 severe TBI patients. The recorded poor prognosis variables included acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury, posttraumatic cerebral infarction and six-month mortality and poor outcome (Glasgow score of 1-3)., Results: Median interlerukin-33 concentration of patients (692 pg/mL) was substantially raised, as compared to controls. Interlerukin-33 concentrations were significantly correlated with Glasgow coma scale (GCS) score and the preceding biomarkers concentrations. Interlerukin-33 concentration > 692 pg/mL emerged as an independent prognostic predictor and its discriminatory capability exceeded those of the above-mentioned inflammatory biomarkers concentrations and was in the range of GCS scores and the aforementioned cell-specific proteins concentrations., Conclusion: Ascending serum interlerukin-33 concentrations could reflect inflammation, severity and worse prognosis following TBI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In-hospital major adverse events (IMAEs), mainly including acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction, are associated with poor prognosis after traumatic brain injury (TBI). Thioredoxin, a potent anti-oxidant, has been identified as an oxidative stress marker. This study was designed to explore the association of serum thioredoxin concentrations with IMAEs of patients with severe TBI., Methods: This prospective, observational study recruited a total of 108 healthy controls and 108 patients with severe TBI. We investigated the possible relation of serum thioredoxin concentrations to IMAEs and trauma severity (reflected by Glasgow coma scale scores) following TBI using a multivariate analysis., Results: Serum thioredoxin concentrations were higher in the patients than in the controls. Serum concentrations of thioredoxin significantly correlated with admission Glasgow coma scale scores. Thioredoxin in serum independently predicted any IMAEs. As compared to admission Glasgow coma scale scores, thioredoxin concentrations had similar areas under receiver operating characteristic curve for any IMAEs., Conclusion: Increased serum thioredoxin concentrations are highly associated with trauma severity and IMAEs, indicating thioredoxin might be a potential prognostic biomarker after TBI., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Macrophage migration inhibitory factor (MIF) is a well-known pro-inflammatory cytokine. Serum MIF concentrations are associated with the severity and prognosis of ischemic stroke., Methods: In this prospective, observational study, white blood cell (WBC) count and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and MIF among 108 severe traumatic brain injury (TBI) patients and 108 controls were measured. We determined whether serum MIF concentrations are associated with inflammation, severity, in-hospital major adverse events (IMAEs) (i.e., in-hospital mortality, acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction) and long-term clinical outcome (i.e., 6-month functional outcome) after TBI., Results: As compared to the controls, serum CRP, IL-6, TNF-α and MIF concentrations were significantly increased. MIF concentrations correlated with WBC count, CRP, IL-6 and TNF-α concentrations and Glasgow coma scale (GCS) scores. MIF in serum was independently associated with IMAEs and long-term clinical outcome. Area under receiver operating characteristic curve of MIF concentrations was similar to GCS scores'. Moreover, MIF concentrations markedly improved the predictive value of GCS scores for 6-month unfavorable outcome., Conclusion: Increased serum MIF concentrations have close relation to inflammation, trauma severity and clinical outcomes, substantializing MIF as a good prognostic biomarker after TBI., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Nesfatin-1 is related to inflammation. Its increased circulating concentrations are associated with the severity and prognosis of subarachnoid hemorrhage. In-hospital major adverse events (IMAEs), including acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction, are correlated with mortality after traumatic brain injury (TBI). The present study was designed to investigate the changes of plasma nesfatin-1 concentrations and further assess its association with inflammation, trauma severity, in-hospital mortality and IMAEs following TBI., Methods: We measured plasma nesfatin-1 concentrations of 100 severe TBI patients and 100 controls. Progressive hemorrhagic injury and posttraumatic cerebral infarction were diagnosed based on a follow-up computerized tomography scan. Acute traumatic coagulopathy was identified according to a coagulation test., Results: Plasma nesfatin-1 concentrations were significantly higher in patients than in controls and associated highly with Glasgow coma scale (GCS) scores and plasma C-reactive protein concentrations. Nesfatin-1 was indicated as an independent predictor for in-hospital mortality and IMAEs. In accordance with area under receiver operating characteristic curve, its predictive value was similar to GCS scores., Conclusion: Increased plasma nesfatin-1 concentrations are associated closely with inflammation, trauma severity and clinical outcomes, indicating that nesfatin-1 might be involved in inflammation and become a good prognostic biomarker following TBI., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Galectin-3 plays a significant role in microglia activation. Its increased circulating concentration has been associated with some inflammatory diseases. In-hospital major adverse events (IMAEs), including acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction, have high prevalence and are strong predictors of mortality after severe traumatic brain injury (STBI). The present study was designed to investigate the relationships between plasma galectin-3 concentrations and trauma severity, in-hospital mortality and IMAEs following STBI., Methods: Plasma galectin-3 concentrations of 100 STBI patients and 100 controls were determined. Diagnosis of progressive hemorrhagic injury and posttraumatic cerebral infarction was made on the follow-up computerized tomography scan. Acute traumatic coagulopathy was defined based on coagulation test., Results: Plasma galectin-3 concentrations were significantly higher in patients as compared to controls and also associated highly with Glasgow Coma Scale scores and plasma C-reactive protein concentrations. Galectin-3 emerged as an independent predictor for in-hospital mortality and IMAEs. Areas under receiver operating characteristic curve of plasma galectin-3 concentrations were similar to those of Glasgow Coma Scale scores for prediction of in-hospital morality and IMAEs., Conclusions: Plasma galectin-3 concentrations have close relation to inflammation, trauma severity and clinical outcome, suggesting that galectin-3 should have the potential to be a good prognostic biomarker after STBI., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Thrombospondin-1 is a homotrimeric glycoprotein with well known functions in hemostasis and angiogenesis. Its expression was increased after experimental intracerebral hemorrhage. We determined whether increased plasma thrombospondin-1 concentrations are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH)., Methods: Plasma thrombospondin-1 concentrations of 118 aSAH patients and 118 age- and gender-matched healthy controls were determined using enzyme-linked immunosorbent assay. Patients were followed up until death or completion of 6months after aSAH. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. Multivariate analyses of significant variables of univariate analyses were performed to determine independent risk factors for the clinical outcomes., Results: Plasma thrombospondin-1 concentrations were significantly higher in aSAH patients than in healthy controls; plasma thrombospondin-1 concentrations were independently associated with clinical severity reflected by the World Federation of Neurological Surgeons score and Fisher score; thrombospondin-1 was identified as an independent predictor of 6-month mortality and 6-month unfavorable outcome; thrombospondin-1 had similar predictive performance compared with the World Federation of Neurological Surgeons score and Fisher score according to receiver operating characteristic curve analysis., Conclusion: Higher plasma thrombospondin-1 concentrations are associated with clinical severity and long-term prognosis of aSAH patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage., Methods: Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2)., Results: Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume., Conclusions: Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Higher plasma copeptin concentrations have been associated with poor clinical outcomes after intracerebral hemorrhage. This study was designed to compare plasma concentrations of copeptin and other biomarkers like myelin basic protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase, phosphorylated axonal neurofilament subunit H, tau and ubiquitin carboxyl-terminal hydrolase L1 for analysis of their prognostic prediction., Methods: We measured plasma concentrations of these biomarkers in 118 healthy controls and in 118 acute patients with a comparison analysis for their prediction of 6-month mortality and unfavorable outcome (modified Rankin Scale score>2)., Results: Plasma concentrations of these biomarkers were statistically significantly higher in all patients than in healthy controls, in non-survivors than in survivors and in patients with unfavorable outcome than with favorable outcome. Areas under receiver operating characteristic curves of plasma concentrations of these biomarkers were similar to those of the National Institute of Health Stroke Scale score for prognostic prediction. Plasma copeptin concentration statistically significantly improved the prognostic predictive value of the National Institute of Health Stroke Scale score, but other biomarkers did not., Conclusions: Copeptin may help in the prediction of long-term clinical outcomes after intracerebral hemorrhage., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: High-mobility group box 1 (HMGB1), a marker of inflammation, has been associated with poor outcome of critical illness. The present study was undertaken to investigate the plasma HMGB1 concentrations in patients with traumatic brain injury (TBI) and to analyze the correlation of HMGB1 with TBI outcome., Methods: We performed an observational, clinical study. Plasma HMGB1 concentration of 106 healthy subjects and 106 patients with severe TBI was measured by ELISA. The correlation with 1-y mortality and unfavorable outcome (Glasgow Outcome Scale score of 1-3) was analyzed., Results: Thirty-one patients (29.2%) died and 48 patients (45.3%) had an unfavorable outcome at 1 y after TBI. Plasma HMGB1 level was substantially higher in patients than in healthy controls. A multivariate analysis selected plasma HMGB1 level as an independent predictor for 1-y mortality and unfavorable outcome of patients. A receiver operating characteristic curve analysis showed plasma HMGB1 level statistically significantly predicted 1-y mortality and unfavorable outcome. The prognostic value of HMGB1 was similar to that of Glasgow Coma Scale score for 1-y clinical outcomes., Conclusions: Plasma HMGB1 concentration emerges as a novel biomarker for predicting 1-y clinical outcomes of TBI., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Hyperadiponectinemia or hypoadiponectinemia is associated with different diseases. There is a paucity of data on circulating plasma adiponectin concentrations in human intracerebral hemorrhage (ICH). We investigated the plasma adiponectin concentrations in patients with intracerebral hemorrhage, and analyzed the correlation of adiponectin with the severity of brain injury and early mortality after ICH., Methods: Thirty controls and 86 patients with acute ICH were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Their concentrations were measured by enzyme-linked immunosorbent assay., Results: After ICH, plasma adiponectin level of the patients increased immediately within 6h, peaked within 24h, plateaued at day 2, and decreased gradually thereafter. It was substantially higher than that in the controls in a period of 7 days. A multivariate analysis showed plasma adiponectin level was an independent predictor for 1-week mortality (odds ratio, 1.199; 95% CI: 1.035-1.389; P=0.015) and that it was associated with Glasgow coma scale (GCS) score (t=-3.596, P=0.001) and plasma C-reactive protein level (t=4.194, P<0.001). A receiver operating characteristic curve identified that a plasma adiponectin level >16.4 μg/ml predicted the 1-week mortality of patients with a sensitivity of 65.6% and a specificity of 90.7% (AUC, 0.789; 95% CI: 0.688-0.870). The predictive value of adiponectin concentration was significantly lower than that of GCS score (P=0.007) and hematoma volume (P=0.022). Adiponectin could not improve the predictive values of GCS score (P=0.317) and hematoma volume (P=0.226)., Conclusions: Adiponectin is an independent indicator of early death and may play an anti-inflammatory role after intracerebral hemorrhage., (Copyright © 2011 Elsevier B.V. All rights reserved.)