Fernández-Sarmiento Jaime, Schlapbach Luregn J, Acevedo Lorena, Santana Carolina Ramírez, Acosta Yeny, Diana Ampudia, Monsalve M, Carcillo Joseph A
Department of Pediatrics and Intensive Care, Fundación Cardioinfantil-Instituto de Cardiología, Universidad de La Sabana, Escuela de Graduados CES, Bogotá, Colombia.
Department of Paediatric Critical Care Research Group, The University of Queensland and Queensland Children's Hospital, Brisbane, QLD, Australia.
Front Pediatr. 2022 Mar 9;10:828968. doi: 10.3389/fped.2022.828968. eCollection 2022.
The early diagnosis and appropriate stratification of sepsis continues to be one of the most important challenges in modern medicine. Single isolated biomarkers have not been enough to improve diagnostic and prognostic strategies and to progress toward therapeutic goals. The information generated by the human genome project has allowed a more holistic approach to the problem. The integration of genomics, transcriptomics, proteomics and metabolomics in sepsis has allowed us to progress in the knowledge of new pathways which are pathophysiologically involved in this disease. Thus, we have understood the importance of and complex interaction between the inflammatory response and the endothelium. Understanding the role of important parts of the microcirculation, such as the endothelial glycocalyx and its interaction with the inflammatory response, has provided early recognition elements for clinical practice that allow the rational use of traditional medical interventions in sepsis. This comprehensive approach, which differs from the classical mechanistic approach, uses systems biology to increase the diagnostic and prognostic spectrum of endothelial damage biomarkers in sepsis, and to provide information on new pathways involved in the pathophysiology of the disease. This, in turn, provides tools for perfecting traditional medical interventions, using them at the appropriate times according to the disease's pathophysiological context, while at the same time discovering new and improved therapeutic alternatives. We have the challenge of transferring this ideal scenario to our daily clinical practice to improve our patients' care. The purpose of this article is to provide a general description of the importance of systems biology in integrating the complex interaction between the endothelium and the inflammatory response in sepsis.
脓毒症的早期诊断和合理分层仍然是现代医学中最重要的挑战之一。单一的生物标志物不足以改善诊断和预后策略,也无法朝着治疗目标取得进展。人类基因组计划所产生的信息使我们能够以更全面的方法来解决这个问题。基因组学、转录组学、蛋白质组学和代谢组学在脓毒症中的整合,使我们在了解该疾病病理生理过程中涉及的新途径方面取得了进展。因此,我们已经认识到炎症反应与内皮之间相互作用的重要性和复杂性。了解微循环重要组成部分的作用,如内皮糖萼及其与炎症反应的相互作用,为临床实践提供了早期识别要素,有助于在脓毒症中合理使用传统医学干预措施。这种综合方法不同于经典的机械论方法,它利用系统生物学来扩大脓毒症中内皮损伤生物标志物的诊断和预后范围,并提供有关该疾病病理生理学中涉及的新途径的信息。反过来,这又为完善传统医学干预措施提供了工具,根据疾病的病理生理背景在适当的时候使用这些措施,同时发现新的和改进的治疗选择。我们面临着将这种理想情况转化为日常临床实践以改善患者护理的挑战。本文的目的是总体描述系统生物学在整合脓毒症中内皮与炎症反应之间复杂相互作用方面的重要性。