Revolution in sepsis: a symptoms-based to a systems-based approach?

IF 9 2区 医学 Q1 CELL BIOLOGY Journal of Biomedical Science Pub Date : 2024-05-30 DOI:10.1186/s12929-024-01043-4
Geoffrey P Dobson, Hayley L Letson, Jodie L Morris
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Abstract

Severe infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy and multiple organ dysfunction. Males appear to have a higher risk of mortality than females. Currently, there are few or no effective drug therapies to protect the brain, maintain the blood brain barrier, resolve excessive inflammation and reduce secondary injury in other vital organs. We propose a major reason for lack of progress is a consequence of the treat-as-you-go, single-nodal target approach, rather than a more integrated, systems-based approach. A new revolution is required to better understand how the body responds to an infection, identify new markers to detect its progression and discover new system-acting drugs to treat it. In this review, we present a brief history of sepsis followed by its pathophysiology from a systems' perspective and future opportunities. We argue that targeting the body's early immune-driven CNS-response may improve patient outcomes. If the barrage of PAMPs and DAMPs can be reduced early, we propose the multiple CNS-organ circuits (or axes) will be preserved and secondary injury will be reduced. We have been developing a systems-based, small-volume, fluid therapy comprising adenosine, lidocaine and magnesium (ALM) to treat sepsis and endotoxemia. Our early studies indicate that ALM therapy shifts the CNS from sympathetic to parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces inflammation, corrects coagulopathy, and maintains tissue O2 supply. Future research will investigate the potential translation to humans.

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败血症的革命:从基于症状的方法到基于系统的方法?
严重感染和败血症是医疗急症。高发病率和高死亡率与中枢神经系统功能障碍、过度炎症、免疫受损、凝血功能障碍和多器官功能障碍有关。男性的死亡风险似乎高于女性。目前,保护大脑、维持血脑屏障、消除过度炎症和减少其他重要器官二次损伤的有效药物疗法很少或根本没有。我们认为,缺乏进展的一个主要原因是 "随治随走 "的单一节点目标方法,而不是更加综合、基于系统的方法。我们需要一场新的革命,以更好地了解人体如何对感染做出反应,确定检测感染进展的新标记物,并发现治疗感染的新系统作用药物。在这篇综述中,我们将简要介绍败血症的历史,然后从系统的角度介绍其病理生理学和未来的机遇。我们认为,针对机体早期免疫驱动的中枢神经系统反应可能会改善患者的预后。如果能在早期减少 PAMPs 和 DAMPs 的冲击,我们认为多个中枢神经系统-器官回路(或轴)将会得到保护,继发性损伤也会减少。我们一直在开发一种基于系统的小容量液体疗法,包括腺苷、利多卡因和镁(ALM),用于治疗败血症和内毒素血症。我们的早期研究表明,ALM疗法能使中枢神经系统从交感神经主导转向副交感神经主导,维持心血管-内皮糖萼耦合,减轻炎症反应,纠正凝血病变,并维持组织的氧气供应。未来的研究将探讨将这种疗法应用于人体的可能性。
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来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
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