title: Sepsis: Something old, something new, and a systems view.
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.
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Rami
authors.initials: R
authors.lastname: Namas
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.forename: Rajaie
authors.initials: R
authors.lastname: Namas
authors.forename: Gary
authors.initials: G
authors.lastname: An
authors.forename: John
authors.initials: J
authors.lastname: Doyle
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Dick
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Jacono
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Androulakis
authors.forename: Gary F
authors.initials: GF
authors.lastname: Nieman
authors.forename: Steve
authors.initials: S
authors.lastname: Chang
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
mesh_terms: D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008954:Models, Biological; D017711:Nonlinear Dynamics; D018805:Sepsis / Q000503:physiopathology*; D049490:Systems Biology