Longitudinal change of serum AIM2 levels after aneurysmal subarachnoid hemorrhage and its prognostic significance: a two-center prospective cohort study.

Absent in melanoma 2 (AIM2) is implicated in neuroinflammation. Here, we explored the prognostic significance of serum AIM2 in human aneurysmal subarachnoid hemorrhage (aSAH). We conducted a consecutive enrollment of 127 patients, 56 of whom agreed with blood-drawings not only at admission but also at days 1, 2, 3, 5, 7 and 10 days after aSAH. Serum AIM2 levels of patients and 56 healthy controls were measured. Disease severity was assessed using the modified Fisher scale (mFisher) and World Federation of Neurological Surgeons Scale (WFNS). Neurological outcome at poststroke 90 days was evaluated via the modified Rankin Scale (mRS). Univariate analysis and multivariate analysis were sequentially done to ascertain relationship between serum AIM2 levels, severity, delayed cerebral ischemia (DCI) and 90-day poor prognosis (mRS scores of 3-6). Patients, in comparison to controls, had a significant elevation of serum AIM2 levels at admission and at days 1, 2, 3, 5, 7 and 10 days after aSAH, with the highest levels at days 1, 2, 3 and 5. AIM2 levels were independently correlated with WFNS scores and mFisher scores. Significantly higher serum AIM2 levels were detected in patients with a poor prognosis than in those with a good prognosis, as well as in patients with DCI than in those without DCI. Moreover, serum AIM2 levels independently predicted a poor prognosis and DCI, and were linearly correlated with their risks. Using subgroup analysis, there were no significant interactions between serum AIM2 levels and age, gender, hypertension and so on. There were substantially high predictive abilities of serum AIM2 for poor prognosis and DCI under the receiver operating characteristic curve. The combination models of DCI and poor prognosis, in which serum AIM2, WFNS scores and mFisher scores were incorporated, showed higher discriminatory efficiencies than anyone of the preceding three variables. Moreover, the models are delineated using the nomogram, and performed well under the calibration curve and decision curve. Serum AIM2 levels, with a substantial enhancement during early phase after aSAH, are closely related to bleeding severity, poor 90-day prognosis and DCI of patients, substantializing serum AIM2 as a potential prognostic biomarker of aSAH.

Huperzine A ameliorates neurological deficits after spontaneous subarachnoid hemorrhage through endothelial cell pyroptosis inhibition.

Spontaneous subarachnoid hemorrhage (SAH) is a kind of hemorrhagic stroke which causes neurological deficits in survivors. Huperzine A has a neuroprotective effect, but its role in SAH is unclear. Therefore, we explore the effect of Huperzine A on neurological deficits induced by SAH and the related mechanism. In this study, Evans blue assay, TUNEL staining, immunofluorescence, western blot analysis, and ELISA are conducted. We find that Huperzine A can improve neurological deficits and inhibit the apoptosis of nerve cells in SAH rats. Huperzine A treatment can improve the upregulation of brain water content, damage of blood-brain barrier, fibrinogen and matrix metalloprotein 9 expressions and the downregulation of ZO-1 and occludin expressions induced by SAH. Huperzine A inhibit the expressions of proteins involved in pyroptosis in endothelial cells in SAH rats. The increase in MDA content and decrease in SOD activity in SAH rats can be partly reversed by Huperzine A. The ROS inducer H 2O 2 can induce pyroptosis and inhibit the expressions of ZO-1 and occludin in endothelial cells, which can be blocked by Huperzine A. In addition, the increase in the entry of p65 into the nucleus in endothelial cells can be partly reversed by Huperzine A. Huperzine A may delay the damage of blood-brain barrier in SAH rats by inhibiting oxidative stress-mediated pyroptosis and tight junction protein expression downregulation through the NF-κB pathway. Overall, Huperzine A may have clinical value for treating SAH.

α-MSH as a potential biomarker of severity and prognosis after intracerebral hemorrhage: A prospective cohort study.

BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) exerts anti-inflammatory and brain protective effects. We determined plasma α-MSH concentrations and discovered the relationship between plasma α-MSH concentrations and severity plus clinical outcome after intracerebral hemorrhage (ICH). METHODS: A total of 117 ICH patients and 117 healthy controls were included in this study. Glasgow coma scale (GCS) score and hematoma volume were recorded to assess disease severity. We used Glasgow outcome scale (GOS) score to evaluate the 3-month clinical prognosis. And multivariate analysis was done to discern the relation of plasma α-MSH concentrations to disease severity plus poor prognosis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability. RESULTS: Plasma α-MSH concentrations in ICH patients, compared with healthy controls, were significantly decreased (median, 25.37 vs 46.80 pg/ml; P < 0.001), and were independently correlated with GCS score (t = 4.091, P < 0.001). Plasma α-MSH concentrations were highly correlated with GOS scores (ρ = 0.548, P < 0.001), were substantially lower with poor prognosis (GOS scores 1-3) than good prognosis, and efficiently discriminated patients at risk of poor prognosis (AUC ROC, 0.793; 95 % CI: 0.709-0.863). Using Youden method, plasma α-MSH concentrations < 23.63 pg/ml predicted poor prognosis with sensitivity of 72.7 % and specificity of 82.2 %. Alternatively, plasma α-MSH concentrations emerged as an independent predictor of poor prognosis with odds ratio of 0.888 (95 % CI: 0.793-0.995; P = 0.040). CONCLUSION: Plasma α-MSH concentrations are significantly associated with disease severity and poor 3-month prognosis in patients with ICH, indicating that plasma α-MSH may serve as a useful potential prognostic biomarker for ICH.

Omi inhibition ameliorates neuron apoptosis and neurological deficit after subarachnoid hemorrhage in rats.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe neurological emergency, resulting in cognitive impairments and threatening human's health. Currently, SAH has no effective treatment. It is urgent to search for an effective therapy for SAH. OBJECTIVE: To explore the expression of Omi protein after subarachnoid hemorrhage in rats. METHODS: SAH rat model was established by injecting blood into the prechiasmatic cistern. Neurological deficit was assessed by detecting neurological deficit scores and brain tissue water contents. Apoptotic cells were evaluated by TUNEL staining and IHC staining. Omi and Cleaved caspase 3 expressions in nerve cells were determined by double staining using IF. Apoptosis-related proteins were measured by Western blotting assay. RESULTS: SAH rat model was successfully established, showing more apoptotic cells and high neurological deficit scores in SAH rat. In SAH rat model, Omi expression in nerve cells was elevated and the upregulation of Omi mainly occurred in cytoplasm, accompanied by the degradation of XIAP and the increased cleaved caspase 3/9 and cleaved PARP. Once treated with UCF-101, a specific inhibitor of Omi, the increased cell apoptosis, left/right brain moisture contents and neurological deficits were notably reversed in SAH rat brain. Of note, SAH-induced the increases of apoptosis-related protein in nerve cells were also rescued by the administration of UCF-101. CONCLUSIONS: UCF-101-mediated Omi inhibition decreased the degradation of XIAP and subsequently inhibited the activation of apoptosis-related proteins, decreased nerve cell apoptosis, leading to the improvement on early brain injury in SAH rat. UCF-101-based Omi inhibition may be used to treat SAH with great potential application.

MerTK inhibits the activation of the NLRP3 inflammasome after subarachnoid hemorrhage by inducing autophagy.

The NLR family pyrin domain-containing 3 (NLRP3) multiprotein complex is associated with neuroinflammation and poor prognosis after subarachnoid hemorrhage (SAH). Accumulating evidence shows that Mer tyrosine kinase (MerTK) alleviates inflammatory responses via a negative feedback mechanism. However, the contribution and function of MerTK in SAH remain to be determined. In this study, we explored the role of MerTK during microglial NLRP3 inflammasome activation and evaluated its contribution to the outcome of SAH in mice. Activating MerTK with growth arrest-specific 6 (Gas6) alleviated brain edema, neuronal degeneration and neurological deficits after SAH by regulating neuroinflammation. Gas6 did not change the mRNA levels of Nlrp3 or Casp1 but decreased the protein expression of NLRP3, cleaved caspase1 (p20), interleukin-1ß and interleukin-18. Furthermore, Gas6 increased the expression of Beclin1, the ratio of LC3-II/LC3-I and the level of autophagic flux. Inhibiting autophagy with 3-MA reversed the inhibition of NLRP3 inflammasome activation and diminished the neuroprotective effects of Gas6. Thus, MerTK activation may exert protective effects by limiting neuroinflammation and promoting neurological recovery after SAH via autophagy induction.

Prognostic significance of serum translocator protein in patients with traumatic brain injury.

BACKGROUND: Translocator protein (TP) is related to inflammation and is involved in brain injury. The objective of this study was to ascertain whether serum TP concentrations are associated with the severity and prognosis of traumatic brain injury (TBI). METHODS: We quantified the serum concentrations of TP in 106 healthy controls and 106 patients with severe TBI. Recorded prognostic variables included acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury, posttraumatic cerebral infarction, 6-month mortality and 6-month poor outcome (Glasgow Outcome Scale score of 1-3). Trauma severity was assessed by Glasgow coma scale (GCS) score. Extent of inflammatory response was indicated by serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and C-reactive protein (CRP) concentrations. RESULTS: Patients had significantly higher serum TP concentrations than controls. Among patients, serum TP concentrations strongly and independently correlated with GCS score and serum IL-6, TNF-a and CRP concentrations. Serum TP was identified as an independent predictor for the preceding prognostic variables, its prognostic predictive ability was similar to that of GCS score and it also significantly improved prognostic predictive ability of GCS score. CONCLUSION: Serum TP may be intimately linked with in inflammation, disease progression and poor prognosis in TBI patients.

Clinical relevance of cleaved RAGE plasma levels as a biomarker of disease severity and functional outcome in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cleaved receptor for advanced glycation end-products (cRAGE) has been introduced as a new inflammatory marker. We clarified the associations between cRAGE levels, disease severity and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this prospective, observational study, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) were quantified in 108 aSAH patients and 108 controls. The level of cRAGE was calculated by subtracting the level of esRAGE from that of sRAGE. World Federation of Neurological Surgeons (WFNS) score, modified Fisher score, and Hunt Hess (HH) score were recorded to assess aSAH severity. Relationship between plasma cRAGE levels and 6-month poor outcome (Glasgow Outcome Scale score of 1-3) was assess using multivariate analysis. RESULTS: Plasma cRAGE levels were significantly higher in patients than in controls. Its levels were significantly correlated with WNFS score, modified Fisher score and HH score of patients. Plasma cRAGE emerged as an independent predictor for 6-month poor outcome. Area under receiver operating characteristic curve (AUC) of this biomarker was similar to those of WNFS score, modified Fisher score and HH score. Moreover, it significantly improved AUCs of WNFS score, modified Fisher score and HH score. CONCLUSIONS: Plasma cRAGE levels are highly associated with the severity and poor prognosis in aSAH.

Comparison of plasma copeptin and multiple biomarkers for assessing prognosis of patients with aneurysmal subarachnoid hemorrhage.

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.

Serum periostin concentrations and outcomes after severe traumatic brain injury.

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.

Serum macrophage migration inhibitory factor concentrations correlate with prognosis of traumatic brain injury.

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.

Serum thioredoxin and in-hospital major adverse events after traumatic brain injury.

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.

The prognostic value of plasma nesfatin-1 concentrations in patients with traumatic brain injury.

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.

The change of plasma galectin-3 concentrations after traumatic brain injury.

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.

The prognostic value of plasma thrombospondin-1 concentrations after aneurysmal subarachnoid hemorrhage.

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.

Plasma 8-iso-Prostaglandin F2α concentrations and outcomes after acute intracerebral hemorrhage.

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.

Comparison of the performances of copeptin and multiple biomarkers in long-term prognosis of severe traumatic brain injury.

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.

Plasma copeptin level predicts acute traumatic coagulopathy and progressive hemorrhagic injury after traumatic brain injury.

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.

Prognostic significance of plasma copeptin detection compared with multiple biomarkers in intracerebral hemorrhage.

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.

Plasma leptin level predicts hematoma growth and early neurological deterioration after acute intracerebral hemorrhage.

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.