Sepsis: rethinking the approach to clinical research
Sepsis: rethinking the approach to clinical research
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DOI：
10.1189/jlb.0607380
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发表时间：
2008-03-01
影响因子：
5.5
通讯作者：
Marshall, John C.
中科院分区：
文献类型：
--
作者：
Marshall, John C.
脓毒症的临床综合征包括一组高度异质性的临床病症，其在部位、细菌学、甚至感染的存在方面以及随着临床综合征在宿主中的演变而变化。调节介导脓毒症的宿主反应的策略的临床试验首次开始于25年前。随后的工作中不断出现令人失望的记录，只有一种新的治疗方法被批准用于临床。然而，这些商业上的失望掩盖了一个充满活力的新知识体系，它澄清了先天免疫反应的生物学，其错乱的表达是脓毒症的原因，并为脓毒症临床研究的传统模式的失败提供了重要的新见解。这篇综述强调了基础生物学的进展，并强调了临床研究的见解，这些研究可能会指出将对先天免疫的理解转化为有效治疗全球发病率和死亡率的主要原因的新的和更有效的方法。
The clinical syndrome of sepsis encompasses a highly heterogeneous group of clinical disorders, varying with respect to the site, bacteriology, and even presence of infection and with the clinical syndrome evolving in the host. Clinical trials of strategies to modulate the host response that mediates sepsis were first initiated 25 years ago. A continuing record of disappointment has characterized subsequent work, and only a single new therapy has been licensed for clinical use. Yet, these commercial disappointments obscure a vibrant body of new knowledge that has clarified the biology of the innate immune response whose deranged expression is responsible for sepsis and that has provided important new insights into the failings of the traditional model of clinical research in sepsis. This review highlights advances in basic biology and underlines insights from clinical research that may point to new and more effective ways of translating an understanding of innate immunity into effective treatments for a leading cause of global morbidity and mortality.