The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding
Open accessAbstract
Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed.
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Cites
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Cited by
The 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
Calfee, C. S., Delucchi, K., Parsons, P. E., Thompson, B. T., Ware, L. B., & Matthay, M. A. (2014) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(14)70097-9 · Cited by 1,544
Liu, S., Wang, Z.-F., Su, Y.-S., Ray, R. S., Jing, X.-H., Wang, Y.-Q., & Ma, Q. (2020) · Neuron · doi:10.1016/j.neuron.2020.07.015 · Cited by 385
Endothelial barrier dysfunction in septic shock
Opal, S. M., & van der Poll, T. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12331 · Cited by 353
Hou, J., Zhang, J., Cui, P., Zhou, Y., Liu, C., Wu, X., Ji, Y., Wang, S., Cheng, B., Ye, H., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci135197 · Cited by 239
Metadata
- Authors
- Iskander, K. N., Osuchowski, M. F., Stearns-Kurosawa, D. J., Kurosawa, S., Stepien, D., Valentine, C., & Remick, D. G.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2013-07
- Volume
- 93
- Issue
- 3
- Pages
- 1247-1288
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2142093121
- Cited by
- 453
- References
- 29
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- green
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- Iskander, K. N., Osuchowski, M. F., Stearns-Kurosawa, D. J., Kurosawa, S., Stepien, D., Valentine, C., & Remick, D. G. (2013). Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding. Physiological Reviews. https://doi.org/10.1152/physrev.00037.2012
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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