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Sepsis: Something old, something new, and a systems view

Namas, Rami and Zamora, Ruben and Namas, Rajaie and An, Gary and Doyle, John and Dick, Thomas E. and Jacono, Frank J. and Androulakis, Ioannis P. and Nieman, Gary F. and Chang, Steve and Billiar, Timothy R. and Kellum, John A. and Angus, Derek C. and Vodovotz, Yoram (2012) Sepsis: Something old, something new, and a systems view. Journal of Critical Care, 27 (3). 314.e1-314.e11. ISSN 0883-9441.

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Sepsis is a clinical syndrome characterized by a multisystem response to a microbial pathogenic insult consisting of a mosaic of interconnected biochemical, cellular, and organ-organ interaction networks. A central thread that connects these responses is inflammation that, while attempting to defend the body and prevent further harm, causes further damage through the feed-forward, proinflammatory effects of damage-associated molecular pattern molecules. In this review, we address the epidemiology and current definitions of sepsis and focus specifically on the biologic cascades that comprise the inflammatory response to sepsis. We suggest that attempts to improve clinical outcomes by targeting specific components of this network have been unsuccessful due to the lack of an integrative, predictive, and individualized systems-based approach to define the time-varying, multidimensional state of the patient. We highlight the translational impact of computational modeling and other complex systems approaches as applied to sepsis, including in silico clinical trials, patient-specific models, and complexity-based assessments of physiology.

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Additional Information:© 2012 Elsevier Inc. Available online 27 July 2011. This work was supported, in part, by the National Institutes of Health grants R01GM67240, P50GM53789, R33HL089082, R01HL080926, R01AI080799, R01HL76157, 3R01GM034695-25S1, and R01GM082974; National Institute on Disability and Rehabilitation Research grant H133E070024; the Veterans Administration Research Service; as well as grants from the Commonwealth of Pennsylvania, the Pittsburgh Lifesciences Greenhouse, and the Pittsburgh Tissue Engineering Initiative.
Funding AgencyGrant Number
National Institute on Disability and Rehabilitation ResearchH133E070024
Veterans Administration Research ServiceUNSPECIFIED
Commonwealth of PennsylvaniaUNSPECIFIED
Pittsburgh Lifesciences GreenhouseUNSPECIFIED
Pittsburgh Tissue Engineering InitiativeUNSPECIFIED
Subject Keywords:Sepsis; Inflammatory response; Physiologic variability; Mathematical model
Issue or Number:3
Record Number:CaltechAUTHORS:20120702-142216264
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Official Citation:Rami Namas, Ruben Zamora, Rajaie Namas, Gary An, John Doyle, Thomas E. Dick, Frank J. Jacono, Ioannis P. Androulakis, Gary F. Nieman, Steve Chang, Timothy R. Billiar, John A. Kellum, Derek C. Angus, Yoram Vodovotz, Sepsis: Something old, something new, and a systems view, Journal of Critical Care, Volume 27, Issue 3, June 2012, Pages 314.e1-314.e11, ISSN 0883-9441, 10.1016/j.jcrc.2011.05.025.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:32237
Deposited By: Jason Perez
Deposited On:03 Jul 2012 14:36
Last Modified:03 Oct 2019 03:59

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