HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis

HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis
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DOI:
10.1007/s00134-008-1032-9
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发表时间:
2008-06-01
影响因子:
38.9
通讯作者:
Ruokonen, Esko
Ruokonen, Esko
中科院分区:
医学1区
文献类型:
--
作者:
Karlsson, Sari;Pettila, Ville;Ruokonen, Esko

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目的:探讨高迁移率族蛋白B1(HMGB 1)对严重脓毒症患者住院病死率的预测价值。研究设计:芬兰24个ICU的前瞻性观察性队列研究。患者:247例严重脓毒症成人患者。测量和主要结果:从基线时的247名患者和72小时后的210名患者中抽取血液样本进行HMGB 1分析。平均APACHE II和SAPS II评分分别为24(SD 9)和44(SD 17)。住院死亡率为26%。首先通过半定量Western免疫印迹(WB)分析测定血清HMGB 1浓度。第0天的中位HMGB 1浓度为108%(IQR 98.5-119),72 h后为107%(IQR 98.8-120),与健康对照组不同(分别为97.5%,IQR 91.3-106.5; p = 0.028和0.019)。通过ELISA(在170名患者的亚组中)对样本进行再分析,以通过WB确认结果。健康对照的中位浓度为0.65 ng/ml(IQR 0.51-1.0)。这低于严重脓毒症患者(3.6 ng/ml,IQR 1.9-6.5,p < 0.001)。HMGB 1浓度(WB和ELISA)在医院幸存者和非幸存者之间没有差异。在ROC分析中,第0天和第72 h的HMGB 1水平(WB)与住院死亡率相关,曲线下面积分别为0.51和0.56(95%CI 0.40-0.61和0.47-0.65)。结论:血清HMGB 1浓度在严重脓毒症患者中升高,但在幸存者和非幸存者之间没有差异,并且不能预测住院死亡率。
Objective: To study the predictive value of high mobility group box-1 protein ( HMGB1) and hospital mortality in adult patients with severe sepsis. Study design: Prospective observational cohort study in 24 ICUs in Finland. Patients: Two hundred and forty-seven adult patients with severe sepsis. Measurements and main results: Blood samples for HMGB1 analyses were drawn from 247 patients at baseline and from 210 patients 72 h later. The mean APACHE II and SAPS II scores were 24 ( SD 9) and 44 ( SD 17), respectively. The hospital mortality was 26%. The serum HMGB1 concentrations were measured first by semi-quantitative Western immunoblotting ( WB) analysis. The median HMGB1 concentration on day 0 was 108% ( IQR 98.5-119) and after 72 h 107% ( IQR 98.8-120), which differed from healthy controls ( 97.5%, IQR 91.3-106.5; p = 0.028 and 0.019, respectively). The samples were reanalysed by ELISA ( in a subgroup of 170 patients) to confirm the results by WB. The median concentration in healthy controls was 0.65 ng/ml ( IQR 0.51-1.0). This was lower than in patients with severe sepsis ( 3.6 ng/ml, IQR 1.9-6.5, p < 0.001). HMGB1 concentrations ( WB and ELISA) did not differ between hospital survivors and non-survivors. In ROC analyses for HMGB1 levels ( WB) on day 0 and 72 h with respect to hospital mortality, the areas under the curve were 0.51 and 0.56 ( 95% CI 0.40-0.61 and 0.47-0.65). Conclusions: Serum HMGB1 concentrations were elevated in patients with severe sepsis, but did not differ between survivors and non-survivors and did not predict hospital mortality.