title: An integrated clinico-metabolomic model improves prediction of death in sepsis.
abstract: Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would ultimately die differed markedly from those of patients who would survive. The different profiles of proteins and metabolites clustered into the following groups: fatty acid transport and β-oxidation, gluconeogenesis, and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of five metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis.
authors.affiliation: National Center for Genome Resources, Santa Fe, NM 87505, USA.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Langley
authors.forename: Ephraim L
authors.initials: EL
authors.lastname: Tsalik
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: van Velkinburgh
authors.forename: Seth W
authors.initials: SW
authors.lastname: Glickman
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Rice
authors.forename: Chunping
authors.initials: C
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Lawrence
authors.initials: L
authors.lastname: Carin
authors.forename: Arturo
authors.initials: A
authors.lastname: Suarez
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.forename: Debra H
authors.initials: DH
authors.lastname: Freeman
authors.forename: Mu
authors.initials: M
authors.lastname: Wang
authors.forename: Jinsam
authors.initials: J
authors.lastname: You
authors.forename: Jacob
authors.initials: J
authors.lastname: Wulff
authors.forename: J Will
authors.initials: JW
authors.lastname: Thompson
authors.forename: M Arthur
authors.initials: MA
authors.lastname: Moseley
authors.forename: Stephanie
authors.initials: S
authors.lastname: Reisinger
authors.forename: Brian T
authors.initials: BT
authors.lastname: Edmonds
authors.forename: Brian
authors.initials: B
authors.lastname: Grinnell
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Dinwiddie
authors.forename: Neil A
authors.initials: NA
authors.lastname: Miller
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Saunders
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Soden
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Rogers
authors.forename: Lee
authors.initials: L
authors.lastname: Gazourian
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fredenburgh
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Massaro
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Baron
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.forename: G Ralph
authors.initials: GR
authors.lastname: Corey
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
authors.forename: Charles B
authors.initials: CB
authors.lastname: Cairns
authors.forename: Ronny M
authors.initials: RM
authors.lastname: Otero
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.forename: Emanuel P
authors.initials: EP
authors.lastname: Rivers
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Woods
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
mesh_terms: D000368:Aged; D000465:Algorithms; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D008962:Models, Theoretical; D040901:Proteomics / Q000379:methods*; D018805:Sepsis / Q000378:metabolism* / Q000401:mortality*