The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis.
The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis.
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DOI：
10.1186/cc9290
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Aird WC
中科院分区：
文献类型：
--
作者：
Shapiro NI;Schuetz P;Yano K;Sorasaki M;Parikh SM;Jones AE;Trzeciak S;Ngo L;Aird WC
先前的报告表明，内皮激活是脓毒症发病机制中的一个重要过程。我们研究了内皮细胞激活的生物标志物与脓毒症严重程度、器官功能障碍（序贯器官衰竭评估[SOFA]评分）以及死亡之间的关联。
这是一项前瞻性观察研究，纳入了2005年2月至2008年11月期间在一所城市学术医疗中心急诊科因临床怀疑感染就诊的成年患者（年龄18岁及以上）。在急诊科就诊时采集血液，检测内皮细胞激活的生物标志物，即可溶性类fms酪氨酸激酶 - 1（sFlt - 1）、纤溶酶原激活物抑制剂 - 1（PAI - 1）、sE - 选择素、可溶性细胞间黏附分子（sICAM - 1）和可溶性血管细胞黏附分子（sVCAM - 1）。分析了生物标志物与脓毒症严重程度、器官功能障碍和住院死亡率这些结果之间的关联。
共纳入221例患者：32%为无器官功能障碍的脓毒症，30%为无休克的严重脓毒症，32%为感染性休克，6%为急诊科未感染的对照患者。所有目标生物标志物（sFlt - 1、PAI - 1、sE - 选择素、sICAM - 1和sVCAM - 1）与脓毒症严重程度之间均存在关联，P < 0.05。我们发现所有生物标志物之间存在显著的相互关联，其中sFlt - 1与sE - 选择素之间的相关性最强（r = 0.55，P < 0.001），sFlt - 1与PAI - 1之间的相关性也很强（r = 0.56，P < 0.001）。在内皮细胞激活生物标志物中，sFlt - 1与SOFA评分的关联最强（r = 0.66，P < 0.001），其对严重脓毒症的受试者工作特征曲线下面积最高，为0.82，对死亡率为0.91。
内皮细胞激活标志物与脓毒症严重程度、器官功能障碍和死亡率相关。更好地理解内皮反应及相关生物标志物可能会促使制定更准确预测结果的策略，并开发针对脓毒症的新型内皮导向疗法。
Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death. This is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and in-hospital mortality were analyzed. A total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91. Markers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
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影响因子：
4.8
作者：
Kim, I;Moon, SO;Koh, GY
通讯作者：
Koh, GY
影响因子：
8.8
作者：
Leone, M;Boutière, B;Dignat-George, F
通讯作者：
Dignat-George, F
DOI：
10.1186/cc7866
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
作者：
Kümpers P;van Meurs M;David S;Molema G;Bijzet J;Lukasz A;Biertz F;Haller H;Zijlstra JG
通讯作者：
Zijlstra JG
影响因子：
38.9
作者：
Garcia-Segarra, Gloria;Espinosa, Gerard;Nicolas, Josep-Maria
通讯作者：
Nicolas, Josep-Maria
影响因子：
38.9
作者：
Janssens, U;Graf, C;Hanrath, P
通讯作者：
Hanrath, P