title: Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome.
abstract: OBJECTIVE
  To provide an appraisal of the evolving paradigms in the pathophysiology of sepsis and propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research.
  
  
  METHODS
  Literature search using PubMed, MEDLINE, EMBASE, and Google Scholar.
  
  
  RESULTS
  Sepsis remains one of the most debilitating and expensive illnesses, and its prevalence is not declining. What is changing is our definition(s), its clinical course, and how we manage the septic patient. Once thought to be predominantly a syndrome of over exuberant inflammation, sepsis is now recognized as a syndrome of aberrant host protective immunity. Earlier recognition and compliance with treatment bundles has fortunately led to a decline in multiple organ failure and in-hospital mortality. Unfortunately, more and more sepsis patients, especially the aged, are suffering chronic critical illness, rarely fully recover, and often experience an indolent death. Patients with chronic critical illness often exhibit "a persistent inflammation-immunosuppression and catabolism syndrome," and it is proposed here that this state of persisting inflammation, immunosuppression and catabolism contributes to many of these adverse clinical outcomes. The underlying cause of inflammation-immunosuppression and catabolism syndrome is currently unknown, but there is increasing evidence that altered myelopoiesis, reduced effector T-cell function, and expansion of immature myeloid-derived suppressor cells are all contributory.
  
  
  CONCLUSIONS
  Although newer therapeutic interventions are targeting the inflammatory, the immunosuppressive, and the protein catabolic responses individually, successful treatment of the septic patient with chronic critical illness and persistent inflammation-immunosuppression and catabolism syndrome may require a more complementary approach.
authors.affiliation: All authors: Department of Surgery, University of Florida College of Medicine, Gainesville, FL.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Mira
authors.forename: Lori F
authors.initials: LF
authors.lastname: Gentile
authors.forename: Brittany J
authors.initials: BJ
authors.lastname: Mathias
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.forename: Scott C
authors.initials: SC
authors.lastname: Brakenridge
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Mohr
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Moore
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D035843:Biomedical Research; D002908:Chronic Disease / Q000628:therapy; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology*; D008660:Metabolism / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology*; D013577:Syndrome