Division of Hematology, University of British Columbia, Vancouver General Hospital, 855 12th Ave W, Vancouver, BC V5Z 1M9, Canada.
Crit Care. 2012 Jan 16;16(1):R7. doi: 10.1186/cc11145.
A strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.
The objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.
Sixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.
Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.
针对内皮细胞（EC）活化标志物作为有临床意义的生物标志物，以改善脓毒症患者的诊断、预后评估或风险分层，具有强有力的生物学依据。
本研究旨在综述将 EC 活化标志物用作脓毒症预后生物标志物的文献。通过关键词“sepsis”和任何可搜索字段中的任何确定的内皮衍生生物标志物，在 MEDLINE 上搜索出版物。所有评估反映 EC 活化的标志物的临床研究均被纳入。排除评估其他内皮功能障碍外源性介质的研究和疟疾及发热性中性粒细胞减少症患者的研究。
确定了 61 项符合纳入标准的研究。总体而言，已发表的研究报告表明，多种 EC 衍生分子与脓毒症的诊断呈正相关，支持 EC 活化在脓毒症中的关键作用。多项研究还报告了与死亡率和疾病严重程度的正相关，但这些结果不如脓毒症的存在那样一致。然而，很少有研究报告这些分子作为脓毒症中具有临床相关性的生物标志物的阈值或接收者操作特征。
多种内皮衍生分子与人类脓毒症的存在呈正相关，与其他临床重要结局呈可变相关。这些生物标志物的临床应用受到缺乏检测标准化、未知的接收者操作特征和缺乏验证的限制。需要进行更多的大型前瞻性临床试验，以确定内皮激活标志物在脓毒症患者管理中的临床应用价值。
