The DOI matches its Crossref record; 292 of the 292 references it cites were found in a registry or an index.
Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Boldt, J., Menges, T., Kuhn, D., Diridis, C., & Hempelmann, G. (1995) · Intensive Care Medicine · doi:10.1007/bf01701475 · Cited by 78
RetractedThe third international consensus definitions for sepsis and septic shock (Sepsis-3).
Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G. R., Chiche, J.-D., Coopersmith, C. M., et al. (2016) · JAMA · doi:10.1001/jama.2016.0287 · Cited by 28,250
Self-citationBone, R. C., Balk, R. A., Cerra, F. B., Dellinger, R. P., Fein, A. M., Knaus, W. A., Schein, R. M. H., & Sibbald, W. J. (1992) · Chest · doi:10.1378/chest.101.6.1644 · Cited by 13,198
Rudd, K. E., Johnson, S. C., Agesa, K. M., Shackelford, K. A., Tsoi, D., Kievlan, D. R., Colombara, D. V., Ikuta, K. S., Kissoon, N., Finfer, S., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(19)32989-7 · Cited by 7,971
Mizgerd, J. P., Kubo, H., Kutkoski, G. J., Bhagwan, S. D., Scharffetter-Kochanek, K., Beaudet, A. L., & Doerschuk, C. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.8.1357 · Cited by 7,306
Of Mice and Not Men: Differences between Mouse and Human Immunology
Mestas, J., & Hughes, C. C. W. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2731 · Cited by 3,822
Schweickert, W. D., Pohlman, M. C., Pohlman, A. S., Nigos, C., Pawlik, A. J., Esbrook, C. L., Spears, L., Miller, M., Franczyk, M., Deprizio, D., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60658-9 · Cited by 3,339
Genomic responses in mouse models poorly mimic human inflammatory diseases
Seok, J., Warren, H. S., Cuenca, A. G., Mindrinos, M. N., Baker, H. V., Xu, W., Richards, D. R., McDonald-Smith, G. P., Gao, H., Hennessy, L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222878110 · Cited by 3,005
2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference
Conference, F. T. I. S. D., Levy, M. M., Fink, M. P., Marshall, J. C., Abraham, E., Angus, D., Cook, D., Cohen, J., Opal, S. M., Vincent, J.-L., et al. (2003) · Intensive Care Medicine · doi:10.1007/s00134-003-1662-x · Cited by 2,871
Redefine statistical significance
Benjamin, D. J., Berger, J. O., Johannesson, M., Nosek, B. A., Wagenmakers, E.-J., Berk, R., Bollen, K. A., Brembs, B., Brown, L., Camerer, C., et al. (2017) · Nature Human Behaviour · doi:10.1038/s41562-017-0189-z · Cited by 2,772
Research works printed but not linked: 13
- Balboa E, Saavedra‐Leiva F, Cea LA, Vargas AA, Ramirez V, Escamilla R, Saez JC, Regueira T (2018) Sepsis‐induced channelopathy in skeletal muscles is associated with expression of non‐selective channels. Shock 49: 221–228 · doi:10.1097/shk.0000000000000916
- Fleischmann C, Thomas‐Rueddel DO, Hartmann M, Hartog CS, Welte T, Heublein S, Dennler U, Reinhart K (2016) Hospital incidence and mortality rates of sepsis. Dtsch Arztebl Int 113: 159–166
- Gogos C, Kotsaki A, Pelekanou A, Giannikopoulos G, Vaki I, Maravitsa P, Adamis S, Alexiou Z, Andrianopoulos G, Antonopoulou A et al (2010) Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection. Crit Care 14: R96 · doi:10.1186/cc9031
- Hara N, Chijiiwa M, Yara M, Ishida Y, Ogiwara Y, Inazu M, Kuroda M, Karlsson M, Sjovall F, Elmér E, Uchino H (2015) Metabolomic analyses of brain tissue in sepsis induced by cecal ligation reveal specific redox alterations‐protective effects of the oxygen radical scavenger edaravone. Shock 44: 578–584 · doi:10.1097/shk.0000000000000465
- Hassan FI, Didari T, Khan F, Mojtahedzadeh M, Abdollahi M (2018) The role of epigenetic alterations involved in sepsis: an overview. Curr Pharm Des 24: 2862–2869 · doi:10.2174/1381612824666180903114253
- Johansen ME, Johansson PI, Ostrowski SR, Bestle MH, Hein L, Jensen AL, Søe‐Jensen P, Andersen MH, Steensen M, Mohr T et al (2015) Profound endothelial damage predicts impending organ failure and death in sepsis. Semin Thromb Hemost 41: 16–25 · doi:10.1055/s-0034-1398377
- Kapetanovic R, Parlato M, Fitting C, Quesniaux V, Cavaillon JM, Adib‐Conquy M (2011) Mechanisms of TNF induction by heat‐killed Staphylococcus aureus differ upon the origin of mononuclear phagocytes. Am J Physiol Cell Physiol 300: C850–C859 · doi:10.1152/ajpcell.00187.2010
- Lipton J, Fossler D (1974) Fever produced in the squirrel monkey by intravenous and intracerebral endotoxin. Am J Physiol 226: 1022–1027 · doi:10.1152/ajplegacy.1974.226.5.1022
- Reithmair M, Buschmann D, Märte M, Kirchner B, Hagl D, Kaufmann I, Pfob M, Chouker A, Steinlein OK, Pfaffl MW et al (2017) Cellular and extracellular miRNAs are blood‐compartment‐specific diagnostic targets in sepsis. J Cell Mol Med 21: 2403–2411 · doi:10.1111/jcmm.13162
- Skirecki T, Mikaszewska‐Sokolewicz M, Hoser G, Zielińska‐Borkowska U (2016) The early expression of HLA‐DR and CD64 myeloid markers is specifically compartmentalized in the blood and lungs of patients with septic shock. Mediators Inflamm 2016: 1–8 · doi:10.1155/2016/3074902
- Sriskandan S, Moyes D, Cohen J (1996) Detection of circulating bacterial superantigen and lymphotoxin‐alpha in patients with streptococcal toxic‐shock syndrome. Lancet 348: 1315–1316 · doi:10.1016/s0140-6736(05)65800-x
- Waterhouse A, Leslie DC, Bolgen DE, Lighbown S, Dimitrakakis N, Cartwright MJ, Seiler B, Lighbown K, Smith K, Lombardo P et al (2018) Modified clinical monitoring assessment criteria for multi‐organ failure during bacteremia and sepsis progression in a pig model. Advan Crit Care Med 1: 002
- Wong HR, Sweeney TE, Lindsell CJ (2017b) Simplification of a septic shock endotyping strategy for clinical application. Am J Respir Crit Care Med 195: 263–265 · doi:10.1164/rccm.201607-1535le
Cited by
Cerebral dysfunctions caused by sepsis during ageing
Manabe, T., & Heneka, M. T. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00643-7 · Cited by 191
COVID-19 and earlier pandemics, sepsis, and vaccines: A historical perspective
Cavaillon, J.-M., & Osuchowski, M. F. (2021) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2021.04.003 · Cited by 17
Self-citationEnteral nutrition in septic shock: a call for a paradigm shift
Patel, J. J., Lopez-Delgado, J. C., Stoppe, C., & McClave, S. A. (2024) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000001134 · Cited by 9
Metadata
- Authors
- Cavaillon, J., Singer, M., & Skirecki, T.
- Venue
- EMBO Molecular Medicine
- Published
- 2020-03-16
- Volume
- 12
- Issue
- 4
- Pages
- e10128-e10128
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- OpenAlex
- W3012116029
- Cited by
- 319
- References
- 292
- FWCI
- 22.12
- Type
- journal article
- Language
- en
- Open access
- gold
- Licence
- creativecommons.org/licenses/by/4.0/ (tdm)
- creativecommons.org/licenses/by/4.0/ (vor)
- Funders
- Polish National Science Center (2013/11/N/NZ6/02581, UMO‐2016/23/D/NZ6/02554)
- Institut Pasteur
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Sepsis therapies: learning from 30 years of failure of translational research to propose new leads. https://app.cochat.ai/papers/10.15252/emmm.201810128
- The paper
- Cavaillon, J., Singer, M., & Skirecki, T. (2020). Sepsis therapies: learning from 30 years of failure of translational research to propose new leads. EMBO Molecular Medicine. https://doi.org/10.15252/emmm.201810128
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
