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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. https://resolver.caltech.edu/CaltechAUTHORS:20120702-142216264

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jcrc.2011.05.025DOIUNSPECIFIED
http://www.sciencedirect.com/science/article/pii/S0883944111002292PublisherUNSPECIFIED
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.
Funders:
Funding AgencyGrant Number
NIHR01GM67240
NIHP50GM53789
NIHR33HL089082
NIHR01HL080926
NIHR01AI080799
NIHR01HL76157
NIH3R01GM034695-25S1
NIHR01GM082974
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
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120702-142216264
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
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:03 Jul 2012 14:36
Last Modified:03 Oct 2019 03:59

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