Cain David J, Del Arroyo Ana Gutierrez, Ackland Gareth L
Clinical Physiology, Department of Medicine, University College London, London, UK.
J Intensive Care Soc. 2015 May;16(2):154-163. doi: 10.1177/1751143714564826. Epub 2015 Jan 7.
Translational research in critically ill human patients presents many methodological challenges. Diagnostic uncertainty, coupled with poorly defined comorbidities, make the identification of a suitable control population for case-control investigations an arguably insurmountable challenge. Healthy volunteer experiments using endotoxin infusion as an inflammatory model are methodologically robust, but fail to replicate the onset of, and diverse therapeutic interventions associated with, sepsis/trauma. Animal models are also limited by many of these issues. Major elective surgery addresses many of these shortfalls and offers a key model for exploring the human biology underlying the sepsis syndrome. Surgery triggers highly conserved features of the human inflammatory response that are common to both tissue damage and infection. Surgical patients sustain a predictable and relatively high incidence of sepsis, particularly within the 'higher risk' group. The collection of preoperative samples enables each patient to act as their own control. Thus, the surgical model offers unique and elegant experimental design features that provide an important translational bridge between the basic biological understanding afforded by animal laboratory models and the de novo presentation of human sepsis.
危重症患者的转化研究面临诸多方法学挑战。诊断的不确定性，再加上合并症定义不明确，使得为病例对照研究确定合适的对照人群成为一项几乎无法克服的挑战。以内毒素输注作为炎症模型的健康志愿者实验在方法学上很可靠，但无法复制脓毒症/创伤的发病情况以及与之相关的各种治疗干预措施。动物模型也受到许多此类问题的限制。大型择期手术解决了许多这些不足，并为探索脓毒症综合征背后的人类生物学提供了一个关键模型。手术引发了人类炎症反应中高度保守的特征，这些特征在组织损伤和感染中都很常见。手术患者脓毒症的发生率可预测且相对较高，尤其是在“高风险”组中。术前样本的采集使每个患者都能作为自己的对照。因此，手术模型提供了独特而精妙的实验设计特点，在动物实验室模型提供的基础生物学理解与人类脓毒症的全新表现之间搭建了一座重要的转化桥梁。
