The DOI matches its Crossref record; 93 of the 93 references it cites were found in a registry or an index.
Animal models of sepsis: Why does preclinical efficacy fail to translate to the clinical setting?
Abstract
OBJECTIVE: To postulate reasons as to why the benefits seen with novel therapies in animal models of sepsis fail to translate to the clinical setting. DATA SOURCE: MEDLINE searches and relevant book chapters. DATA SUMMARY: Thousands of preclinical trials performed over more than five decades have failed to find more than a handful of drugs and techniques that significantly improve outcomes in clinical sepsis. We review current concepts surrounding the variety of animal models used today, ranging from simple models of acute toxemia to more complex models of abdominal sepsis. Differences between animal and human populations are also examined including species, age, comorbidity, and the use of supportive therapies. Finally, we examine differences between preclinical and clinical trial design, and the potential for experimental and publication bias. CONCLUSIONS: Animal models of sepsis are still too heterogeneous with regard to type of insult, duration, and supportive therapy to be regarded as representative of the human condition. Using standardized animal models may eliminate some of the differences between animal and human studies, allowing a greater degree of translation.
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Angus, D. C., Linde-Zwirble, W. T., Lidicker, J., Clermont, G., Carcillo, J., & Pinsky, M. R. (2001) · Critical Care Medicine · doi:10.1097/00003246-200107000-00002 · Cited by 8,503
Dellinger, R. P., Levy, M. M., Carlet, J. M., Bion, J., Parker, M. M., Jaeschke, R., Reinhart, K., Angus, D. C., Brun-Buisson, C., Beale, R., et al. (2008) · Intensive Care Medicine · doi:10.1007/s00134-007-0934-2 · Cited by 6,772
Kumar, A., Roberts, D., Wood, K. E., Light, B., Parrillo, J. E., Sharma, S., Suppes, R., Feinstein, D., Zanotti, S., Taiberg, L., et al. (2006) · Critical Care Medicine · doi:10.1097/01.ccm.0000217961.75225.e9 · Cited by 6,109
The epidemiology of sepsis in the United States from 1979 through 2000
Martin, G. S., Mannino, D. M., Eaton, S., & Moss, M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022139 · Cited by 5,841
The Pathophysiology and Treatment of Sepsis
Hotchkiss, R. S., & Karl, I. E. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021333 · Cited by 4,097
The immunopathogenesis of sepsis
Cohen, J. (2002) · Nature · doi:10.1038/nature01326 · Cited by 2,742
Shock and Tissue Injury Induced by Recombinant Human Cachectin
Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., et al. (1986) · Science · doi:10.1126/science.3764421 · Cited by 2,549
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Tracey, K. J., Fong, Y., Hesse, D. G., Manogue, K. R., Lee, A. T., Kuo, G. C., Lowry, S. F., & Cerami, A. (1987) · Nature · doi:10.1038/330662a0 · Cited by 2,448
Beutler, B., Milsark, I. W., & Cerami, A. C. (1985) · Science · doi:10.1126/science.3895437 · Cited by 2,352
Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412
Suntharalingam, G., Perry, M. R., Ward, S., Brett, S. J., Castello-Cortes, A., Brunner, M. D., & Panoskaltsis, N. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa063842 · Cited by 2,164 · cited 1×
“Sometimes, as graphically demonstrated by the unexpected cytokine storm witnessed in human volunteers given an anti-CD28 monoclonal antibody (108), preclinical studies may fail to highlight potentially life-threatening complications in humans.”
Background
Cited by
Sepsis: a roadmap for future research
Cohen, J., Vincent, J.-L., Adhikari, N. K. J., Machado, F. R., Angus, D. C., Calandra, T., Jaton, K., Giulieri, S., Delaloye, J., Opal, S., et al. (2015) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(15)70112-x · Cited by 992
Laboratory mice born to wild mice have natural microbiota and model human immune responses
Rosshart, S. P., Herz, J., Vassallo, B. G., Hunter, A., Wall, M. K., Badger, J. H., McCulloch, J. A., Anastasakis, D. G., Sarshad, A. A., Leonardi, I., et al. (2019) · Science · doi:10.1126/science.aaw4361 · Cited by 572
The inflammatory response in sepsis
Bosmann, M., & Ward, P. A. (2013) · Trends in Immunology · doi:10.1016/j.it.2012.09.004 · Cited by 558
Fink, M. P. (2014) · Virulence · doi:10.4161/viru.26083 · Cited by 391
Gender differences in sepsis: Cardiovascular and immunological aspects
Angele, M. K., Pratschke, S., Hubbard, W. J., & Chaudry, I. H. (2014) · Virulence · doi:10.4161/viru.26982 · Cited by 344
Metadata
- Authors
- Dyson, A., & Singer, M.
- Venue
- Critical Care Medicine
- Published
- 2009-01
- Volume
- 37
- Issue
- Supplement
- Pages
- S30-S37
- ISSN
- 0090-3493 (ISSN-L)
- OpenAlex
- W2022745533
- Cited by
- 273
- References
- 93
- FWCI
- 10.73
- Type
- journal article
- Language
- en
- Open access
- closed
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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.
