Sepsis therapies: learning from 30 years of failure of translational research to propose new leads

Abstract Sepsis has been identified by the World Health Organization (WHO) as a global health priority. There has been a tremendous effort to decipher underlying mechanisms responsible for organ failure and death, and to develop new treatments. Despite saving thousands of animals over the last three...

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Main Authors: Jean‐Marc Cavaillon, Mervyn Singer, Tomasz Skirecki
Format: Article
Language:English
Published: Springer Nature 2020-03-01
Series:EMBO Molecular Medicine
Subjects:
Online Access:https://doi.org/10.15252/emmm.201810128
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author Jean‐Marc Cavaillon
Mervyn Singer
Tomasz Skirecki
author_facet Jean‐Marc Cavaillon
Mervyn Singer
Tomasz Skirecki
author_sort Jean‐Marc Cavaillon
collection DOAJ
description Abstract Sepsis has been identified by the World Health Organization (WHO) as a global health priority. There has been a tremendous effort to decipher underlying mechanisms responsible for organ failure and death, and to develop new treatments. Despite saving thousands of animals over the last three decades in multiple preclinical studies, no new effective drug has emerged that has clearly improved patient outcomes. In the present review, we analyze the reasons for this failure, focusing on the inclusion of inappropriate patients and the use of irrelevant animal models. We advocate against repeating the same mistakes and propose changes to the research paradigm. We discuss the long‐term consequences of surviving sepsis and, finally, list some putative approaches—both old and new—that could help save lives and improve survivorship.
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spelling doaj-art-36873f3afed940c48cc03d7a751ab5d32025-08-24T11:44:14ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-03-0112412410.15252/emmm.201810128Sepsis therapies: learning from 30 years of failure of translational research to propose new leadsJean‐Marc Cavaillon0Mervyn Singer1Tomasz Skirecki2Experimental Neuropathology Unit, Institut PasteurBloomsbury Institute of Intensive Care Medicine, University College LondonLaboratory of Flow Cytometry and Department of Anesthesiology and Intensive Care Medicine, Centre of Postgraduate Medical EducationAbstract Sepsis has been identified by the World Health Organization (WHO) as a global health priority. There has been a tremendous effort to decipher underlying mechanisms responsible for organ failure and death, and to develop new treatments. Despite saving thousands of animals over the last three decades in multiple preclinical studies, no new effective drug has emerged that has clearly improved patient outcomes. In the present review, we analyze the reasons for this failure, focusing on the inclusion of inappropriate patients and the use of irrelevant animal models. We advocate against repeating the same mistakes and propose changes to the research paradigm. We discuss the long‐term consequences of surviving sepsis and, finally, list some putative approaches—both old and new—that could help save lives and improve survivorship.https://doi.org/10.15252/emmm.201810128animal modelscytokine stormpersonalized medicinereprogrammingsepsis
spellingShingle Jean‐Marc Cavaillon
Mervyn Singer
Tomasz Skirecki
Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
EMBO Molecular Medicine
animal models
cytokine storm
personalized medicine
reprogramming
sepsis
title Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
title_full Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
title_fullStr Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
title_full_unstemmed Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
title_short Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
title_sort sepsis therapies learning from 30 years of failure of translational research to propose new leads
topic animal models
cytokine storm
personalized medicine
reprogramming
sepsis
url https://doi.org/10.15252/emmm.201810128
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AT mervynsinger sepsistherapieslearningfrom30yearsoffailureoftranslationalresearchtoproposenewleads
AT tomaszskirecki sepsistherapieslearningfrom30yearsoffailureoftranslationalresearchtoproposenewleads