Journal ArticleDOI
Treatment of Septic Shock with the Tumor Necrosis Factor Receptor:Fc Fusion Protein
Charles J. Fisher,Jan M. Agosti,Steven M. Opal,Stephen F. Lowry,Robert A. Balk,Jerald C. Sadoff,Edward Abraham,Roland M. H. Schein,Ernest Benjamin +8 more
TLDR
In patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.Abstract:
Background A recombinant, soluble fusion protein that is a dimer of an extracellular portion of the human tumor necrosis factor (TNF) receptor and the Fc portion of IgG1 (TNFR:Fc) binds and neutralizes TNF-α and prevents death in animal models of bacteremia and endotoxemia. Methods To evaluate the safety and efficacy of TNFR:Fc in the treatment of septic shock, we conducted a randomized, double-blind, placebo-controlled, multicenter trial. A total of 141 patients were randomly assigned to receive either placebo or a single intravenous infusion of one of three doses of TNFR:Fc (0.15, 0.45, or 1.5 mg per kilogram of body weight). The primary end point was mortality from all causes at 28 days. Results There were 10 deaths among the 33 patients in the placebo group (30 percent mortality), 9 deaths among the 30 patients receiving the low dose of TNFR:Fc (30 percent mortality), 14 deaths among the 29 receiving the middle dose (48 percent mortality), and 26 deaths among the 49 receiving the high dose (53 percent...read more
Citations
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The pathophysiology and treatment of sepsis.
TL;DR: This review examines evolving concepts of sepsis and discusses new and potential therapies, including therapy with activated protein C, stringent control of blood glucose, and early goal-directed therapy to treat cellular oxygen deficit.
Journal ArticleDOI
Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, prospective study
Jl Vincent,A. de Mendonça,Francis Cantraine,Rui Moreno,Jukka Takala,Pm Suter,Cl Sprung,Francis Colardyn,S Blecher +8 more
TL;DR: In this paper, the authors evaluated the use of the Sequential Organ Failure Assessment (SOFA) score in assessing the incidence and severity of organ dysfunction in critically ill patients in ICU.
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TNF‐mediated inflammatory disease
TL;DR: The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of T NF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis.
Journal ArticleDOI
Tumor necrosis factor antagonist mechanisms of action: A comprehensive review
TL;DR: The biology of T NF and related family members are discussed in the context of the potential mechanisms of action of TNF antagonists in a variety of immune-mediated inflammatory diseases.
Journal ArticleDOI
Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock
Thomas Vogl,Klaus Tenbrock,Stephan Ludwig,Nadja Leukert,Christina Ehrhardt,Marieke A. D. van Zoelen,Wolfgang Nacken,Dirk Foell,Tom van der Poll,Clemens Sorg,Johannes Roth +10 more
TL;DR: It is demonstrated that mice lacking Mrp8-Mrp14 complexes are protected from endotoxin-induced lethal shock and Escherichia coli–induced abdominal sepsis, indicating new inflammatory components that amplify phagocyte activation during sepsi upstream of TNFα–dependent effects.
References
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Journal ArticleDOI
Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis
Roger C. Bone,Robert A. Balk,F. B. Cerra,R. P. Dellinger,A. M. Fein,William A. Knaus,Roland M. H. Schein,W. J. Sibbald,WA Knous,J. H. Abrams,G. R. Bernard,JW Biondi,JE Calvin,R Demling,PJ Fahey,CJ Fisher,C Franklin,KJ Gorelick,MA Kelley,DG Maki,JC Marshall,WW Merrill,JP Pribble,EC Rackow,Timothy C. Rodell,JN Sheagren,Michael R. Silver,C. L. Sprung,Richard C. Straube,MJ Tobin,GM Trenholme,DP Wagner,CD Webb,JC Wherry,HP Wiedemann,CH Wortel,M. Kylänpää-Bäck +36 more
Journal ArticleDOI
The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults.
William A. Knaus,Douglas P. Wagner,Elizabeth A. Draper,Jack E. Zimmerman,Marilyn Bergner,Paulo G. Bastos,Carl A. Sirio,Donaldj Murphy,Ted Lotring,Anne M. Damiano +9 more
TL;DR: The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h ofICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed.
Journal ArticleDOI
Shock and tissue injury induced by recombinant human cachectin.
Kevin J. Tracey,Bruce Beutler,Stephen F. Lowry,James P Merryweather,Stephen D. Wolpe,Ian W. Milsark,Robert J. Hariri,Thomas J. Fahey,Alejandro Zentella,J. D. Albert,G. Tom Shires,Anthony Cerami +11 more
TL;DR: It appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.
Journal ArticleDOI
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Kevin J. Tracey,Kevin J. Tracey,Yuman Fong,David G. Hesse,Kirk R. Manogue,Annette T. Lee,George C. Kuo,Stephen F. Lowry,Anthony Cerami +8 more
TL;DR: Protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion, indicating that cachectin is a mediator of fatal bacteraemic shock and suggesting that antibodies against Cachectin offer a potential therapy of life-threatening infection.
Journal ArticleDOI
Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin
TL;DR: The data suggest that cachectin/TNF is one of the principal mediators of the lethal effect of endotoxin, and this effect was dose-dependent and was most effective when the antiserum was administered prior to the injection of the endotoxin.