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.
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.
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脓毒症相关脑病中钙结合蛋白 A8 和肿瘤坏死因子受体相关因子 6 的诊断和预测水平：一项前瞻性观察研究
DOI：
10.4103/0366-6999.185860
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发表时间：
2016-07-20
影响因子：
6.1
通讯作者：
Ai YH
中科院分区：
文献类型：
--
作者：
Zhang LN;Wang XH;Wu L;Huang L;Zhao CG;Peng QY;Ai YH
背景：尽管脓毒症相关性脑病(SAE)的患病率、发病率和死亡率都很高，但人们对它的了解仍然很少。本研究旨在探讨血清钙结合蛋白A8(S100A8)和外周血单个核细胞(PBMC)中肿瘤坏死因子受体相关因子6(TRAF6)在诊断SAE及预测预后中的临床意义。方法：收集2014年7月至2015年3月重症监护病房入院后24小时内的脓毒症患者资料。健康医务人员为对照组。SAE被定义为符合排除标准的脓毒症患者的脑功能障碍。对SAE患者的生化指标、格拉斯哥昏迷评分、急性生理学和慢性健康状况评分II、PBMC中TRAF6、血清S100A8、S100和BGR；以及神经元特异性烯醇化酶进行重新评估。对照组同时检测TRAF6和S100A8。结果：57例入选患者中，29例被诊断为SAE。SAE组S100A8和TRAF6水平均显著高于无脑病组(3.74±3.13比1.08±0.75比0.37±0.14 ng/ml，P<0.01；3.18±1.55比1.02±0.63比0.47±0.10，P<0.01)。S100A8水平为1.93 ng/ml时，受试者工作特征(ROC)曲线诊断SAE的特异度为92.90%，灵敏度为69.00%，曲线下面积为0.86(95%可信区间：0.76~0.95)。TRAF6相对水平1.44为诊断SAE的特异度为85.70%，灵敏度为86.20%，曲线下面积为0.94(95%CI：0.88~0.99)。此外，在ROC曲线中，S100A8水平2.41 ng/ml预测SAE患者28d死亡率的特异度为90.00%，灵敏度为73.70%，曲线下面积为0.88。TRAF6相对水平2.94预测SAE患者28天死亡率的特异度为80.00%，敏感度为68.40%，曲线下面积为0.77。与TRAF6相比，血清S100A8诊断SAE和预测死亡率的特异性较高，但敏感性较低。相比之下，TRAF6对诊断的敏感性较高。结论：SAE患者外周血中S100A8和TRAF6水平升高，可能与SAE的严重程度有关，并可预测SAE的预后。尽管S100A8的敏感性较低，但其诊断SAE的有效性和特异度较高。S100A8可能是诊断SAE和预测预后的较好的生物标志物。
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, S100&bgr;, 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.