title: Diagnostic and Predictive Levels of Calcium-binding Protein A8 and Tumor Necrosis Factor Receptor-associated Factor 6 in Sepsis-associated Encephalopathy: A Prospective Observational Study.
abstract: BACKGROUND
  Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy (SAE) is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 (S100A8) in serum and tumor necrosis factor receptor-associated factor 6 (TRAF6) in peripheral blood mononuclear cells (PBMCs) in diagnosing SAE and predicting its prognosis.
  
  
  METHODS
  Data of septic patients were collected within 24 h after Intensive Care Unit admission from July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfunction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S100A8, S100β, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S100A8 were also measured in the control group.
  
  
  RESULTS
  Of the 57 enrolled patients, 29 were diagnosed with SAE. The S100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy (NE) patients, and higher in NE than that in controls (3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P < 0.01; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P < 0.01). S100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic (ROC) curve, and the area under the curve was 0.86 (95% confidence interval [CI]: 0.76-0.95). TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 (95% CI: 0.88-0.99). In addition, S100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis.
  
  
  CONCLUSIONS
  Peripheral blood levels of S100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.
authors.affiliation: Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan 410008, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Chun-Guang
authors.initials: CG
authors.lastname: Zhao
authors.affiliation: Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Qian-Yi
authors.initials: QY
authors.lastname: Peng
authors.affiliation: Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Ai
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D040501:Calgranulin A / Q000097:blood; D002147:Calmodulin / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D065166:Sepsis-Associated Encephalopathy / Q000097:blood / Q000175:diagnosis*; D048029:TNF Receptor-Associated Factor 6 / Q000097:blood*
chemical_list: D015415:Biomarkers; C428830:CALN1 protein, human; D040501:Calgranulin A; D002147:Calmodulin; D064568:S100 Calcium Binding Protein beta Subunit; D048029:TNF Receptor-Associated Factor 6