RESUMEN
BACKGROUND: Increased plasma copeptin concentrations are related to poor prognosis after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess prognostic significance of plasma copeptin detection compared with glial fibrillary astrocyte protein, myelin basic protein, S100B, phosphorylated axonal neurofilament subunit H, neuron-specific enolase, tau and ubiquitin carboxyl-terminal hydrolase L1 in aSAH. METHODS: We detected plasma concentrations of the aforementioned biomarkers in 105 healthy controls using ELISA. Their predictive ability for symptomatic cerebral vasospasm and 6-month poor outcome (Glasgow Outcome Scale score of 1-3) were compared. RESULTS: Plasma concentrations of the preceding biomarkers were highly correlated with World Federation of Neurological Surgeons subarachnoid hemorrhage scale (WFNS) scores as well as were significantly higher in patients with symptomatic cerebral vasospasm than in those without symptomatic cerebral vasospasm and in patients with poor outcome than in those with good outcome. In terms of area under receiver operating characteristic curve, their predictive value for symptomatic cerebral vasospasm and 6-month poor outcome was in the range of WFNS scores. Plasma copeptin concentration, but not plasma concentrations of other biomarkers, statistically significantly improved the predictive performance of WFNS scores. CONCLUSIONS: Copeptin in plasma might have the potential to be a useful prognostic biomarker for aSAH.
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Glicopéptidos/sangre , Aneurisma Intracraneal/diagnóstico , Hemorragia Subaracnoidea/diagnóstico , Vasoespasmo Intracraneal/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Expresión Génica , Proteína Ácida Fibrilar de la Glía/sangre , Proteína Ácida Fibrilar de la Glía/genética , Glicopéptidos/genética , Humanos , Aneurisma Intracraneal/sangre , Aneurisma Intracraneal/patología , Masculino , Persona de Mediana Edad , Proteína Básica de Mielina/sangre , Proteína Básica de Mielina/genética , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/genética , Fosfopiruvato Hidratasa/sangre , Fosfopiruvato Hidratasa/genética , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/genética , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/patología , Ubiquitina Tiolesterasa/sangre , Ubiquitina Tiolesterasa/genética , Vasoespasmo Intracraneal/sangre , Vasoespasmo Intracraneal/patología , Proteínas tau/sangre , Proteínas tau/genéticaRESUMEN
BACKGROUND: Periostin, a neurite outgrowth-promoting factor, is increasingly expressed in rat brain tissues after cerebral ischemia or subarachnoid hemorrhage. However, periostin concentrations are undetermined in peripheral blood from patients with traumatic brain injury (TBI). METHODS: In this prospective, observational study, serum periostin concentrations were measured in 130 controls and 130 severe TBI patients. We investigated its association with trauma severity reflected by Glasgow Coma Scale (GCS) score and prognosis (i.e., 30-day mortality and 30-day overall survival). RESULTS: As compared with the controls, serum periostin concentrations were significantly increased in the patients [(median, 246.5ng/ml; interquartile range, 164.5-328.6ng/ml) vs. (median, 61.8ng/ml; interquartile range, 37.9-77.9ng/ml), P<0.001]. Periostin concentrations independently correlated with GCS scores (t=-6.199, P<0.001). Serum periostin concentrations higher than 308.2ng/ml predicted 30-day mortality with a sensitivity of 72.4% and a specificity of 78.2% [area under curve, 815; 95% confidence interval (CI), 0.737-0.878]. Periostin concentrations higher than 246.5ng/ml were independently related to 30-day mortality and 30-day overall survival with odds ratio value of 3.829 (95% CI, 1.104-13.281) and hazard ratio value of 5.667 (95% CI, 1.953-16.443) respectively. CONCLUSIONS: Increased serum periostin concentrations clearly reflect trauma severity and mortality following TBI.
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Lesiones Traumáticas del Encéfalo/sangre , Moléculas de Adhesión Celular/sangre , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
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.
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Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/diagnóstico , Factores Inhibidores de la Migración de Macrófagos/sangre , Adolescente , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
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.
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Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/complicaciones , Hospitales , Tiorredoxinas/sangre , Adolescente , Adulto , Anciano , Lesiones Traumáticas del Encéfalo/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
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.
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Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/diagnóstico , Trombospondina 1/sangre , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Análisis Multivariante , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
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.
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Hemorragia Cerebral/sangre , Hemorragia Cerebral/mortalidad , Dinoprost/análogos & derivados , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/mortalidad , Enfermedad Aguda , Anciano , Biomarcadores/sangre , Hemorragia Cerebral/diagnóstico , Dinoprost/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Accidente Cerebrovascular/diagnóstico , Resultado del TratamientoRESUMEN
Enhanced blood levels of copeptin correlate with poor clinical outcomes after acute critical illness. This study aimed to compare the prognostic performances of 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 in severe traumatic brain injury. We recruited 102 healthy controls and 102 acute patients with severe traumatic brain injury. Plasma concentrations of these biomarkers were determined using enzyme-linked immunosorbent assay. Their prognostic predictive performances of 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score of 1-3) were compared. 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 Glasgow Coma Scale score for prognostic prediction. Except plasma copeptin concentration, other biomarkers concentrations in plasma did not statistically significantly improve prognostic predictive value of Glasgow Coma Scale score. Copeptin levels may be a useful tool to predict long-term clinical outcomes after severe traumatic brain injury and have a potential to assist clinicians.
Asunto(s)
Lesiones Encefálicas/sangre , Lesiones Encefálicas/diagnóstico , Glicopéptidos/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
Higher plasma copeptin levels correlate with poor clinical outcomes after traumatic brain injury. Nevertheless, their links with acute traumatic coagulopathy and progressive hemorrhagic injury are unknown. Therefore, we aimed to investigate the relationship between plasma copeptin levels, acute traumatic coagulopathy and progressive hemorrhagic injury in patients with severe traumatic brain injury. We prospectively studied 100 consecutive patients presenting within 6h from head trauma. Progressive hemorrhagic injury was present when the follow-up computerized tomography scan reported any increase in size or number of the hemorrhagic lesion, including newly developed ones. Acute traumatic coagulopathy was defined as an activated partial thromboplastic time greater than 40s and/or international normalized ratio greater than 1.2 and/or a platelet count less than 120×10(9)/L. We measured plasma copeptin levels on admission using an enzyme-linked immunosorbent assay in a blinded fashion. In multivariate logistic regression analysis, plasma copeptin level emerged as an independent predictor of progressive hemorrhagic injury and acute traumatic coagulopathy. Using receiver operating characteristic curves, we calculated areas under the curve for progressive hemorrhagic injury and acute traumatic coagulopathy. The predictive performance of copeptin was similar to that of Glasgow Coma Scale score. However, copeptin did not obviously improve the predictive value of Glasgow Coma Scale score. Thus, copeptin may help in the prediction of progressive hemorrhagic injury and acute traumatic coagulopathy after traumatic brain injury.
Asunto(s)
Hemorragia Encefálica Traumática/sangre , Coagulación Intravascular Diseminada/sangre , Glicopéptidos/sangre , Enfermedad Aguda , Adulto , Hemorragia Encefálica Traumática/complicaciones , Coagulación Intravascular Diseminada/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Índices de Gravedad del TraumaRESUMEN
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.
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Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico , Glicopéptidos/sangre , Anciano , Biomarcadores/sangre , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Oxymatrine, a potent monosomic alkaloid extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.). possesses anti-inflammatory activittyes. This study was designed to investigate the effects of oxymatrine on nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)-dependent inflammatory responses in lipopolysaccharide (LPS)-activated microglia. In this paper, BV2 microglia were pretreated with different concentrations of oxymatrine (1, 10 and 20 µg/mL) for 30 min as followed by stimulation with LPS (1 µg/mL) for different times (30 min, 1 h, 3 h, and 6 h). Concentrations of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) in supernatant, mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), cytosolic inhibitor of kappa B-alpha (I-κBα) and phospho- I-κBα and nuclear p65 protein levels, and the phosphorylations of MAPK molecules such as extracellular-signal-regulated kinase (ERK) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK) were determined. It was shown that oxymatrine inhibited the productions of NO, PGE2, TNF-α, IL-1ß and IL-6, attenuated the mRNA levels of iNOS and COX-2, suppressed the phosphorylation of I-κBα in cytosol, decreased the nuclear levels of p65, and also blocked ERK, p38 and JNK pathway in LPS-stimulated BV2 microglial cells in a dose-dependent manner. According to the results; It is suggested that oxymatrine may attenuate inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in the brain disorders.
RESUMEN
Higher plasma leptin levels have been associated with poor clinical outcomes after intracerebral hemorrhage. Nevertheless, their links with hematoma growth and early neurological deterioration are unknown. Therefore, we aimed to investigate the relationship between plasma leptin levels, hematoma growth, and early neurological deterioration in patients with acute intracerebral hemorrhage. We prospectively studied 102 consecutive patients with acute spontaneous basal ganglia hemorrhage presenting within 6h from symptoms onset. Significant hematoma growth was defined as hematoma enlargement >33% at 24h. Early neurological deterioration was defined as an increase of ≥4 points in National Institute of Health Stroke Scale score at 24h from symptoms onset. We measured plasma leptin levels on admission using an enzyme-linked immunosorbent assay in a blinded fashion. In multivariate logistic regression analysis, plasma leptin level emerged as the independent predictor of hematoma growth (odds ratio, 1.182; 95% confidence interval, 1.061-2.598; P=0.008) and early neurological deterioration (odds ratio, 1.193; 95% confidence interval, 1.075-2.873; P=0.004). Using receiver operating characteristic curves, we calculated areas under the curve for hematoma growth (area under curve, 0.844; 95% confidence interval, 0.759-0.908) and early neurological deterioration (area under curve, 0.857; 95% confidence interval, 0.774-0.918). The predictive performance of leptin was similar to, but did not obviously improve that of hematoma volume. Thus, leptin may help in the prediction of hematoma growth and early neurological deterioration after intracerebral hemorrhage.
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Hemorragia de los Ganglios Basales/sangre , Hemorragia de los Ganglios Basales/fisiopatología , Hematoma/sangre , Leptina/sangre , Anciano , Área Bajo la Curva , Hemorragia de los Ganglios Basales/diagnóstico , Biomarcadores/sangre , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Hematoma/diagnóstico , Hematoma/fisiopatología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Curva ROCRESUMEN
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.
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Adiponectina/sangre , Hemorragia Cerebral/sangre , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Hemorragia Cerebral/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
High plasma copeptin levels are associated with mortality after intracerebral hemorrhage (ICH). However, there is a paucity of data available on whether copeptin is an independent prognostic marker of mortality. Thus, we sought to furthermore evaluate this relation. Thirty healthy 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. Its concentration was measured by enzyme-linked immunosorbent assay. After ICH, plasma copeptin level in patients increased during the 6-h period immediately, peaked in 24h, decreased gradually thereafter, and was substantially higher than that in healthy controls during the 7-day period. A multivariate analysis showed plasma copeptin level was an independent predictor for 1-week mortality (odds ratio, 1.013; 95% confidence interval (CI), 1.003-1.023; P=0.009) and positively associated with hematoma volume (t=6.616, P<0.001). A receiver operating characteristic curve identified that a baseline plasma copeptin level >577.5pg/mL predicted 1-week mortality with 87.5% sensitivity and 72.2% specificity (area under curve (AUC), 0.873; 95% CI, 0.784-0.935). The AUC of the copeptin concentration was similar to those of Glasgow Coma Scale (GCS) scores and hematoma volumes (P=0.136 and 0.280). However, copeptin did not statistically significantly improve the AUCs of GCS scores and hematoma volumes (P=0.206 and 0.333). Hence, increased plasma copeptin level is associated with hematoma volume and an independent prognostic marker of mortality after ICH.