Usefulness of Serum Translocator Protein as a Potential Predictive Biochemical Marker of Three-Month Cognitive Impairment After Acute Intracerebral Hemorrhage: A Prospective Observational Cohort Study.

Background: Translocator protein (TSPO) is a biomarker of neuroinflammation and brain injury. This study aimed to ascertain the potential of serum TSPO as a predictor of cognitive impairment after acute intracerebral hemorrhage (ICH). Methods: In this prospective observational cohort study, 276 patients with supratentorial ICH were randomly assigned to two groups (184 patients in the study group and 92 in the validation group) in a 2:1 ratio. Serum TSPO levels were gauged at admission, and cognitive status was assessed using the Montreal Cognitive Assessment Scale (MoCA) post-stroke 3 months. A MoCA score of < 26 was considered indicative of cognitive impairment. Results: Serum TSPO levels were inversely correlated with MoCA scores (ρ=-0.592; P<0.001). Multivariate linear regression analysis showed that serum TSPO levels were independently associated with MoCA scores (ß, -0.934; 95% confidence interval (CI), -1.412--0.455; VIF, 1.473; P<0.001). Serum TSPO levels were substantially higher in patients with cognitive impairment than in the remaining patients (median, 2.7 versus 1.6 ng/mL; P<0.001). Serum TSPO levels were linearly correlated with the risk of cognitive impairment under a restricted cubic spline (P=0.325) and independently predicted cognitive impairment (odds ratio, 1.589; 95% CI, 1.139-2.216; P=0.016). Subgroup analysis showed that the relationship between serum TSPO levels and cognitive impairment was not markedly influenced by other parameters, such as age, sex, drinking, smoking, hypertension, diabetes mellitus, body mass index, and dyslipidemia (all P for interaction > 0.05). The model, which contained serum TSPO, National Institutes of Health Stroke Scale scores and hematoma volume, performed well under the receiver operating characteristic curve, calibration curve and decision curve, and using the Hosmer-Lemeshow test. This model was validated in the validation group. Conclusion: Serum TSPO level upon admission after ICH was independently associated with cognitive impairment, substantializing serum TSPO as a reliable predictor of post-ICH cognitive impairment.

Prognostic Role of Serum Soluble Tim-3 in Severe Traumatic Brain Injury: A Prospective Observational Study.

Objective: T cell immunoglobulin and mucin domain-3 (Tim-3) may be implicated in neuroinflammation. Herein, we attempted to discern the role of serum soluble (s) Tim-3 as an inflammatory prognostic biomarker of severe traumatic brain injury (sTBI). Methods: In this prospective observational study of 112 sTBI patients and 112 controls, serum sTim-3 levels were determined, Rotterdam computed tomography (CT) classification and Glasgow coma scale (GCS) were selected as the two severity indicators, serum C-reactive protein (CRP) was regarded as an inflammatory biomarker, and poor prognosis was referred to as extended Glasgow outcome scale (GOSE) scores 1-4 at 180 days after trauma. Results: Serum sTim-3 levels were markedly higher in patients than in controls (median, 4.2 ng/mL versus 0.7 ng/mL; P<0.001). Serum sTim-3 levels of patients were independently related to Rotterdam CT scores (ß=1.126), GCS scores (ß=-0.589), serum CRP levels (ß=0.155) and GOSE scores (ß=-0.211). Serum sTim-3 appeared as an independent predictor of post-traumatic 180-day mortality (odds ratio=1.289), overall survival (hazard ratio=1.208) and poor prognosis (odds ratio=1.293). Serum sTim-3 levels discriminated patients at risk of post-injury 180-day mortality and poor prognosis with areas under curve (AUCs) at 0.753 and 0.782, respectively. Serum sTim-3 levels combined with GCS scores and Rotterdam CT scores (AUC=0.869) exhibited significantly higher AUC than Rotterdam CT scores (P=0.026), but not than GCS scores (P=0.181) for death prediction and their combination (AUC=0.895) had significantly higher AUC than GCS scores (P=0.036) or Rotterdam CT scores (P=0.005) for outcome prediction. Conclusion: Elevated serum sTim-3 levels, in close correlation with traumatic severity and inflammation, are substantially associated with long-term death and poor outcome, indicating that serum sTim-3, as an inflammatory biomarker, may be of clinical significance in severity assessment and prediction of prognosis following sTBI.

Serum hypoxia-inducible factor 1alpha emerges as a prognostic factor for severe traumatic brain injury.

BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1α) is implicated in the cell's response to hypoxia. We investigated whether serum HIF-1α concentrations are correlated with the severity and clinical outcome of severe traumatic brain injury (sTBI). METHODS: Serum HIF-1α concentrations were quantified in 104 sTBI patients and 80 healthy controls. Trauma severity was assessed using Glasgow coma scale (GCS). Glasgow outcome scale (GOS) score of 1-3 at post-trauma 90 days was defined as a poor outcome. Multivariate analyses were performed to discern the relationship between serum HIF-1α concentrations and outcome. RESULTS: Patients displayed significantly higher serum HIF-1α concentrations than controls (median, 294.9 versus 102.7 pg/ml). HIF-1α concentrations were intimately related to GCS scores (r = -0.62) and GOS scores (r = -0.64). 48 patients (46.2%) experienced a poor outcome. Serum HIF-1α concentrations > 280.2 pg/ml significantly distinguished patients with the development of poor outcome with 77.1% sensitivity and 69.6% specificity (AUC, 0.750; 95% CI: 0.655-0.829). Serum HIF-1α concentrations > 280.2 pg/ml emerged as an independent predictor for poor outcome (OR: 4.179; 95% CI: 1.024-17.052). CONCLUSIONS: Serum HIF-1α concentrations are tightly associated with trauma severity and poor 90-day outcome, substantializing serum HIF-1α as a promising prognostic biomarker for sTBI.

Serum CXC chemokine ligand-12 as a potential predictor for in-hospital major adverse events after severe traumatic brain injury.

BACKGROUND: CXC chemokine ligand-12 (CXCL12) is associated with brain inflammation. We attempted to discern whether serum CXCL12 is a promising predictor for in-hospital major adverse events (IMAEs) after traumatic brain injury (TBI), including death, acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction. METHODS: In this prospective, observational study, serum CXCL12 levels were quantified among 117 severe TBI patients. We investigated the relation of CXCL12 levels to IMAEs using a multivariate analysis. RESULTS: Median value of serum CXCL12 concentrations was substantially higher in patients with IMAEs than in other remainders (21.1 vs. 11.6 ng/ml). With an increasing number of IMAEs, serum CXCL12 concentrations were significantly increased (r = 0.702). Serum CXCL12 independently predicted IMAEs (odds ratio, 1.253; 95% CI, 1.100-1.428). Serum CXCL12 concentrations discriminated risk of IMAEs with area under receiver operating characteristic curve of 0.759 (95% CI, 0.672-0.834), its concentrations >16.0 ng/ml distinguished IMAEs with 83.9% sensitivity and 67.2% specificity and its combination with Glasgow coma scale scores produced the best predictive ability compared with each one alone (p = 0.0116 or 0.0004). CONCLUSION: Serum CXCL12 concentrations are independently associated with IMAEs following TBI, substantializing serum CXCL12 as a useful prognostic biomarker for head trauma patients.

Usefulness of serum glucose and potassium ratio as a predictor for 30-day death among patients with severe traumatic brain injury.

BACKGROUND: Serum glucose and potassium ratio (GPR) was recently found to be related to outcome of aneurysmal subarachnoid hemorrhage. This retrospectively study was to investigate the association of serum GPR with mortality in severe traumatic brain injury (sTBI). METHODS: Clinical data were retrospectively reviewed of isolated sTBI patients admitted within 12 h after trauma between January 2014 and January 2019. We analyzed relationships between admission serum GPR and post-traumatic 30-day mortality in addition to admission Glasgow coma scale (GCS) scores. Discriminative ability was evaluated using area under receiver operating characteristic curve (AUC). RESULTS: A total of 146 patients, of whom 37 (25.3%) died within 30 days following trauma, were included. Admission serum GPR emerged as an independent predictor for 30-day mortality (odds ratio, 5.256; 95% confidence interval (CI), 1.111-14.856) and overall survival (hazard ratio, 4.822; 95% CI, 1.157-12.870), with an AUC of 0.777 (95% CI, 0.693-0.835), which was equivalent to that of GCS scores (AUC, 0.831; 95% CI, 0.760-0.888; P = 0.179). There was a significant correlation between admission serum GPR and GCS scores (r2 = 0.293). CONCLUSIONS: Serum GPR in cases of sTBI is substantially associated with trauma severity and 30-day mortality. Therefore, the potential value of serum GPR for predicting short-term mortality of sTBI patients is favorable.

Higher plasma C-type lectin-like receptor 2 concentrations for prediction of higher risk of 30-day mortality in isolated severe blunt traumatic brain injury.

BACKGROUND: Platelet activation is implicated in secondary brain injury following traumatic brain injury (TBI). C-type lectin-like receptor 2 (CLEC-2) is extensively expressed on platelets and participates in platelet activation. We investigate dthe prognostic significance of plasma CLEC-2 in TBI patients. METHODS: One hundred and six patients with isolated severe blunt TBI and 106 healthy controls were prospectively investigated. Plasma CLEC-2 concentrations were detected and Glasgow coma scale (GCS) scores were recorded. The relationship between plasma CLEC-2 concentrations and 30-day mortality in addition to overall survival was determined using multivariate models. RESULTS: Patients exhibited a substantially higher concentration of plasma CLEC-2 than healthy controls. Among patients, plasma CLEC-2 concentrations were remarkably increased in the GCS scores- and Rotterdam computerized tomography classification- dependent manner. As compared with survivors within posttraumatic 30 days, plasma CLEC-2 concentrations were remarkably raised in non-survivors. Rising plasma CLEC-2 concentration was independently associated with an enhanced risk of 30-day mortality and short overall survival time. Plasma CLEC-2 concentrations had a significantly high area under receiver operating characteristic curve for predicting 30-day mortality. CONCLUSIONS: Incremental plasma CLEC-2 concentrations are intimately related to increasing trauma severity, in close association with increased 30-day death, indicating the prognostic role of plasma CLEC-2 in TBI.

A prospective study on serum secreted protein acidic and rich in cysteine-like 1 as a prognostic marker for severe traumatic brain injury.

BACKGROUND: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability with upregulation throughout axonal regeneration. Our study aims to determine the correlation of serum SPARCL1 concentrations with the severity and in-hospital mortality of severe traumatic brain injury (sTBI). METHODS: A total of 102 consecutively recruited patients admitted for sTBI and 102 randomly selected healthy controls were included in this observational prospective study. Serum SPARCL1 concentrations were measured and correlated with Glasgow coma scale (GCS) scores and in-hospital mortality using multivariate analysis. RESULTS: Compared with controls (median, 0.22 ng/ml; interquartile range, 0.19-0.41 ng/ml), patients had significantly higher SPARCL1 concentrations (median, 3.29 ng/ml; interquartile range, 1.88-4.37; P < 0.001). There was an independently correlation between SPARCL1 concentrations and GCS scores (t = -7.011, P < 0.001). We found a high area under receiver operating curve (AUC) of serum SPARCL1 concentrations to predict in-hospital mortality (AUC, 0.822; 95% confidence interval, 0.734-0.891). In the multiple logistic regression analysis, serum SPARCL1 concentrations >3.29 ng/ml was independently associated with in-hospital mortality (odds ratio = 10.052, 95% confidence interval = 1.918-52.686, P = 0.006). CONCLUSIONS: The novel findings of our study are that sTBI patients had an increase of serum SPARCL1 concentrations, and that there is an association between high serum SPARCL1 concentrations and sTBI mortality or trauma severity.

Serum lipocalin-2 concentrations and mortality of severe traumatic brain injury.

BACKGROUND: Lipocalin-2 is related to acute brain injury. We assessed the prognostic value of serum lipocalin-2 in head trauma. METHODS: Blood samples were collected from 115 controls and 115 patients with severe traumatic brain injury. Trauma severity was assessed by Glasgow Coma Scale (GCS) scores at baseline. Thirty-day mortality and overall survival time were recorded. RESULTS: Compared with the controls, serum lipocalin-2 concentrations were significantly increased in the patients. Lipocalin-2 concentrations were independently associated with GCS scores (t=-7.271, P<0.001) and serum C-reactive protein concentrations (t=4.325, P<0.001). Under receiver operating characteristic curve for 30-day mortality, sensitivity and specificity were 85.7% and 63.2% respectively for lipocalin-2 concentrations at a cutoff value of 591ng/ml. Additionally, area under curve (AUC) of lipocalin-2 concentrations [AUC, 0.825; 95% confidence interval (95% CI), 0.743-0.889] was equivalent to that of GCS scores (AUC, 0.869; 95% CI, 0.793-0.925; P=0.413). Moreover, serum lipocalin-2 concentrations >591ng/ml emerged as an independent predictor for 30-day mortality (odds ratio, 4.360; 95% CI, 1.908-12.430) and overall survival (hazard ratio, 3.820; 95% CI, 1.935-10.500). CONCLUSIONS: Enhanced serum concentration of lipocalin-2 at admission is associated with trauma severity and neuroinflammation as well as is a predictor of mortality after head trauma.

High plasma adiponectin levels in patients with severe traumatic brain injury.

BACKGROUND: Adiponectin plays an important role in the regulation of tissue inflammation. There is a paucity of data on circulating plasma adiponectin concentrations in human traumatic brain injury. This study is designed to investigate the potential associations between plasma adiponectin levels and clinical outcomes after traumatic brain injury. METHODS: Plasma adiponectin levels of 86 patients with severe traumatic brain injury and 86 healthy subjects were determined. Clinical outcomes included in-hospital mortality, 6-month mortality and 6-month unfavorable outcome (Glasgow Outcome Scale score of 1-3). RESULTS: Plasma adiponectin levels were significantly higher in patients compared to controls (20.5±5.9 vs. 7.7±2.0µg/ml; P<0.001) and emerged as an independent predictor of in-hospital mortality [odds ratio (OR), 1.318; 95% confidence interval (CI), 1.049-1.629; P=0.008], 6-month mortality (OR, 1.328; 95% CI, 1.082-1.657; P=0.007) and 6-month unfavorable outcome (OR, 1.240; 95% CI, 1.066-1.443; P=0.005) in a multivariate analysis. For predicting these clinical outcomes, areas under receiver operating characteristic curve of plasma adiponectin level were similar to those of Glasgow Coma scale scores (all P>0.05). However, adiponectin did not improve predictive values of Glasgow Coma scale scores (all P>0.05). CONCLUSION: Plasma adiponectin level may represent a novel biomarker for predicting clinical outcomes of traumatic brain injury.

Resistin is associated with mortality in patients with traumatic brain injury.

INTRODUCTION: Recently, we reported that high levels of resistin are present in the peripheral blood of patients with intracerebral hemorrhage and are associated with a poor outcome. However, not much is known regarding the change in plasma resistin and its relation with mortality after traumatic brain injury (TBI). Thus, we sought to investigate change in plasma resistin level after TBI and to evaluate its relation with disease outcome. METHODS: Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5 and 7 after TBI. Its concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Twenty-six patients (27.7%) died from TBI within 1 month. After TBI, plasma resistin level in patients increased during the 6-hour period immediately after TBI, peaked within 24 hours, plateaued at day 2, decreased gradually thereafter and was substantially higher than that in healthy controls during the 7-day period. A forward stepwise logistic regression selected plasma resistin level (odds ratio, 1.107; 95% confidence interval, 1.014-1.208; P = 0.023) as an independent predictor for 1-month mortality of patients. A multivariate linear regression showed that plasma resistin level was negatively associated with Glasgow Coma Scale score (t = -6.567, P < 0.001). A receiver operating characteristic curve identified plasma resistin cutoff level (30.8 ng/mL) that predicted 1-month mortality with the optimal sensitivity (84.6%) and specificity (75.0%) values (area under curve, 0.854; 95% confidence interval, 0.766-0.918; P < 0.001). CONCLUSIONS: Increased plasma resistin level is found and associated with Glasgow Coma Scale score and mortality after TBI.