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Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis

TLDR
Steven M. Opal, MDPierre-Francois Laterre, MDBruno Francois, MDSteven P. LaRosa, MDDerek C. Kalil, MD, MPHMarc Van Nuffelen, MDMelvyn Lynn, PhDDaniel P. Rossignol, PhDJogadish Gogate, PhDMary B. Roberts, MSJanice L. Wheeler, BS, RNJean-Louis Vincent, MD as discussed by the authors
Abstract
Steven M. Opal, MDPierre-Francois Laterre, MDBruno Francois, MDSteven P. LaRosa, MDDerek C. Angus, MD, MPHJean-Paul Mira, MD, PhDXavier Wittebole, MDThierry Dugernier, MDDominique Perrotin, MDMark Tidswell, MDLuis Jauregui, MDKenneth Krell, MDJan Pachl, MDTakeshi Takahashi, MDClaus Peckelsen, MDEdward Cordasco, DOChia-Sheng Chang, MDSandra Oeyen, MDNaoki Aikawa, MD, PhDTatsuya Maruyama, MD, PhDRoland Schein, MDAndre C. Kalil, MD, MPHMarc Van Nuffelen, MDMelvyn Lynn, PhDDaniel P. Rossignol, PhDJogadish Gogate, PhDMary B. Roberts, MSJanice L. Wheeler, BS, RNJean-Louis Vincent, MD, PhDfor the ACCESS Study Group

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Citations
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Journal ArticleDOI

Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012

TL;DR: In critically ill patients in Australia and New Zealand with severe sepsis with and without shock, there was a decrease in mortality from 2000 to 2012, accompanied by changes in the patterns of discharge to home, rehabilitation, and other hospitals.
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Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis

TL;DR: The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in the risk of death.
Journal ArticleDOI

Sepsis and septic shock

TL;DR: With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting.
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Cytokine storm and sepsis disease pathogenesis

TL;DR: The pathophysiology of the cytokine storm is summarized; the type, effects, and kinetics of cytokine production are described; and new promising therapeutic strategies focusing on the endothelium, as a source and a target of cytokines are described.
Journal ArticleDOI

Sepsis: pathophysiology and clinical management

TL;DR: Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients.
References
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Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

TL;DR: Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction, and is especially common in the elderly and is likely to increase substantially as the U.S. population ages.
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MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4

TL;DR: It is reported that a novel molecule, MD-2, is requisite for LPS signaling of TLR4, which is physically associated withTLR4 on the cell surface and confers responsiveness to LPS.
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Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction *

TL;DR: It is demonstrated that TLR4 is involved in lipopolysaccharide signaling and serves as a cell-surface co-receptor for CD14, leading to lipopoly Saccharide-mediated NF-κB activation and subsequent cellular events.
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Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003*

TL;DR: The rate of severe sepsis hospitalization almost doubled during the 11-yr period studied and is considerably greater than has been previously predicted.
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