Strategies to improve drug development for sepsis (Q34436905)

2 August 2017

title

Strategies to improve drug development for sepsis (English)

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2 August 2017

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Mitchell P Fink

1

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2 August 2017

H Shaw Warren

series ordinal

2

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2 August 2017

publication date

5 September 2014

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Nature Reviews Drug Discovery

2 August 2017

published in

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2 August 2017

volume

13

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2 August 2017

issue

10

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2 August 2017

page(s)

741-758

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Cytokines in sepsis: potent immunoregulators and potential therapeutic targets--an updated view

2 August 2017

cites work

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Current trends in inflammatory and immunomodulatory mediators in sepsis

31 March 2020

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The pathophysiology of septic shock

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Oxidative stress and mitochondrial dysfunction in sepsis

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2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference

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Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care

31 March 2020

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The epidemiology of sepsis in the United States from 1979 through 2000

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Benchmarking the incidence and mortality of severe sepsis in the United States

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Sepsis in European intensive care units: results of the SOAP study.

31 March 2020

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Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*.

31 March 2020

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31 March 2020

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Outcome of acute respiratory distress syndrome patients treated with extracorporeal membrane oxygenation and brought to a referral center

31 March 2020

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Survival of septic adults compared with nonseptic adults receiving extracorporeal membrane oxygenation for cardiopulmonary failure: A propensity-matched analysis

31 March 2020

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Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine

31 March 2020

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Sepsis definitions: time for change

31 March 2020

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Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis

31 March 2020

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High plasma level of long pentraxin 3 (PTX3) is associated with fatal disease in bacteremic patients: a prospective cohort study

31 March 2020

1 reference

Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study

31 March 2020

1 reference

Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis

31 March 2020

1 reference

Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis

31 March 2020

1 reference

Interleukin 27 as a sepsis diagnostic biomarker in critically ill adults

31 March 2020

1 reference

Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients: a systematic review and meta-analysis

31 March 2020

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Severe sepsis and septic shock

31 March 2020

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The multifunctional alarmin HMGB1 with roles in the pathophysiology of sepsis and cancer

31 March 2020

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Bench-to-bedside review: Cytopathic hypoxia

31 March 2020

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Association between mitochondrial dysfunction and severity and outcome of septic shock

31 March 2020

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Mitochondrial function in sepsis: acute phase versus multiple organ failure

31 March 2020

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Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach

31 March 2020

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Stealth and mimicry by deadly bacterial toxins

31 March 2020

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Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli

31 March 2020

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Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids

31 March 2020

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Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis

31 March 2020

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Antiinflammatory action of glucocorticoids--new mechanisms for old drugs

31 March 2020

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Predisposing factors for adrenal insufficiency

31 March 2020

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Incidence of adrenal insufficiency and impact of corticosteroid supplementation in critically ill children with systemic inflammatory syndrome and vasopressor-dependent shock

31 March 2020

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Adrenal insufficiency in septic shock

31 March 2020

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Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock

31 March 2020

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Hydrocortisone therapy for patients with septic shock

31 March 2020

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Antibody to Cell Wall Glycolipid of Gram-Negative Bacteria: Induction of Immunity to Bacteremia and Endotoxemia

31 March 2020

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Human Antiserum for Prevention of the Local Shwartzman Reaction and Death from Bacterial Lipopolysaccharides

31 March 2020

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Anti-endotoxin monoclonal antibodies

31 March 2020

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A controlled trial of HA-1A in a canine model of gram-negative septic shock.

31 March 2020

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Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group.

31 March 2020

1 reference

Inhibition of endotoxin response by e5564, a novel Toll-like receptor 4-directed endotoxin antagonist

31 March 2020

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A novel cyclohexene derivative, ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242), selectively inhibits toll-like receptor 4-mediated cytokine production through suppression of intracellular signaling

31 March 2020

1 reference

A recombinant amino terminal fragment of bactericidal/permeability-increasing protein inhibits the induction of leukocyte responses by LPS.

31 March 2020

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Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial

31 March 2020

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Phase 2 trial of eritoran tetrasodium (E5564), a toll-like receptor 4 antagonist, in patients with severe sepsis

31 March 2020

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A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis

31 March 2020

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Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group

31 March 2020

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Recombinant Human Tumor Necrosis Factor Administered as a 24-Hour Intravenous Infusion. A Phase I and Pharmacologic Study

31 March 2020

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Neutralization of tumor necrosis factor in preclinical models of sepsis

31 March 2020

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Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels

31 March 2020

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Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials: a meta-analysis

31 March 2020

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A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice

31 March 2020

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Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial

31 March 2020

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Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group

31 March 2020

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Phase II multicenter clinical study of the platelet-activating factor receptor antagonist BB-882 in the treatment of sepsis

31 March 2020

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Recombinant platelet-activating factor acetylhydrolase to prevent acute respiratory distress syndrome and mortality in severe sepsis: Phase IIb, multicenter, randomized, placebo-controlled, clinical trial

31 March 2020

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Recombinant human platelet-activating factor acetylhydrolase for treatment of severe sepsis: results of a phase III, multicenter, randomized, double-blind, placebo-controlled, clinical trial

31 March 2020

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Disseminated intravascular coagulation and coagulation disorders

31 March 2020

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Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock

31 March 2020

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Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon

31 March 2020

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Efficacy of antithrombin III supplementation in animal models of fulminant Escherichia coli endotoxemia or bacteremia

31 March 2020

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Efficacy and safety of recombinant human activated protein C for severe sepsis

31 March 2020

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Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death

31 March 2020

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Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial.

31 March 2020

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Drotrecogin alfa (activated) in adults with septic shock.

31 March 2020

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Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery.

31 March 2020

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The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830].

31 March 2020

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A phase 2 randomized, double-blind, placebo-controlled study of the safety and efficacy of talactoferrin in patients with severe sepsis

31 March 2020

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Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group

31 March 2020

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Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group

31 March 2020

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Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock

31 March 2020

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Endotoxin-binding and -neutralizing properties of recombinant bactericidal/permeability-increasing protein and monoclonal antibodies HA-1A and E5.

31 March 2020

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Protective effects of anti-O polysaccharide and anti-lipid A monoclonal antibodies on pulmonary hemodynamics.

31 March 2020

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Plasma patterns of tumor necrosis factor-alpha (TNF) and TNF soluble receptors during acute meningococcal infections and the effect of plasma exchange

31 March 2020

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Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study

31 March 2020

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Animal models of sepsis and shock: a review and lessons learned.

31 March 2020

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Preclinical sepsis models

31 March 2020

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31 March 2020

Animal models of sepsis

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Animal models of sepsis and its complications

31 March 2020

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Scavenger receptor class a plays a central role in mediating mortality and the development of the pro-inflammatory phenotype in polymicrobial sepsis

31 March 2020

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Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation

31 March 2020

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Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography

31 March 2020

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Antibiotics delay but do not prevent bacteremia and lung injury in murine sepsis.

31 March 2020

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Inhibition of nitric oxide synthesis improves survival in a murine peritonitis model of sepsis that is not cured by antibiotics alone

31 March 2020

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Inhibition of nitric oxide synthase in experimental gram-negative sepsis.

31 March 2020

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Inhibition of nitric oxide synthase (NOS) aggravates Staphylococcus aureus septicaemia and septic arthritis

31 March 2020

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Cyclooxygenase inhibitors enhance tumour necrosis factor production and mortality in murine endotoxic shock

31 March 2020

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Role for intracellular platelet-activating factor in the circulatory failure in a model of gram-positive shock

31 March 2020

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31 March 2020

Animal models of sepsis

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Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection

31 March 2020

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Resilience to bacterial infection: difference between species could be due to proteins in serum

31 March 2020

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Influence of hypercortisolemia on soluble tumor necrosis factor receptor II and interleukin-1 receptor antagonist responses to endotoxin in human beings*

31 March 2020

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Brief report: shock and multiple-organ dysfunction after self-administration of Salmonella endotoxin

31 March 2020

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Genomic responses in mouse models poorly mimic human inflammatory diseases

31 March 2020

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Reconstituting organ-level lung functions on a chip

31 March 2020

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Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice

31 March 2020

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Aged mice are unable to mount an effective myeloid response to sepsis

31 March 2020

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Galactosamine-induced sensitization to the lethal effects of endotoxin

31 March 2020

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Effect of artificial fever in increasing susceptibility to bacterial endotoxin

31 March 2020

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Unstressing intemperate models: how cold stress undermines mouse modeling

31 March 2020

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Sepsis-induced human lymphocyte apoptosis and cytokine production in "humanized" mice

31 March 2020

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Overcoming current limitations in humanized mouse research

31 March 2020

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The pig: a model for human infectious diseases

31 March 2020

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Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis

31 March 2020

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The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

31 March 2020

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A peptide antagonist of CD28 signaling attenuates toxic shock and necrotizing soft-tissue infection induced by Streptococcus pyogenes

31 March 2020

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A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections: A Randomized Clinical Trial

31 March 2020

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Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis

31 March 2020

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Human genetics: an inflammatory issue

31 March 2020

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Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis

31 March 2020

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Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are associated with fatal outcome in a multicentre, prospective cohort study. Hypothetical impact of tetracyclines

31 March 2020

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A novel role for matrix metalloproteinase-8 in sepsis

31 March 2020

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Matrix metalloproteinase-8 as a potential drug target for the therapy of sepsis

31 March 2020

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Adaptive trial designs: a review of barriers and opportunities

31 March 2020

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Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock

31 March 2020

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A genomic score prognostic of outcome in trauma patients

31 March 2020

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Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors

31 March 2020

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Functional disability 5 years after acute respiratory distress syndrome

31 March 2020

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Pharmacological characterization of FE 202158, a novel, potent, selective, and short-acting peptidic vasopressin V1a receptor full agonist for the treatment of vasodilatory hypotension

31 March 2020

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AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

31 March 2020

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Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

31 March 2020

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Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis.

31 March 2020

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Gastrin-releasing peptide as a molecular target for inflammatory diseases: an update.

31 March 2020

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Glyburide reduces bacterial dissemination in a mouse model of melioidosis

31 March 2020

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Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis

31 March 2020

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Computational drug repositioning: from data to therapeutics

31 March 2020

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The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study

31 March 2020

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A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock

31 March 2020

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Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group.

31 March 2020

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INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group.

31 March 2020

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Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group

31 March 2020

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Confirmatory platelet-activating factor receptor antagonist trial in patients with severe gram-negative bacterial sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. BN 52021 Sepsis Investigator Group

31 March 2020

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Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial

31 March 2020

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Recombinant tissue factor pathway inhibitor in severe community-acquired pneumonia: a randomized trial

31 March 2020

1 reference

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

31 March 2020

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Multicenter, double-blind, placebo-controlled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis

31 March 2020

1 reference

Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial.

31 March 2020

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Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial

31 March 2020

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The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group

31 March 2020

1 reference

Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia

31 March 2020

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Effectiveness of steroid/antibiotic treatment in primates administered LD100 Escherichia coli

31 March 2020

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Granulocyte colony-stimulating factor and antibiotics in the prophylaxis of a murine model of polymicrobial peritonitis and sepsis.

31 March 2020

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Adjunctive efficacy of granulocyte colony-stimulating factor on treatment of Pseudomonas aeruginosa pneumonia in neutropenic and non-neutropenic hosts

31 March 2020

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Relationships between tumour necrosis factor, eicosanoids and platelet-activating factor as mediators of endotoxin-induced shock in mice

31 March 2020

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Effects of UR-12633, a new antagonist of platelet-activating factor, in rodent models of endotoxic shock

31 March 2020

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Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effect on mouse sepsis model

31 March 2020

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Therapeutic effects of TAK-242, a novel selective Toll-like receptor 4 signal transduction inhibitor, in mouse endotoxin shock model.

31 March 2020

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Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis.

31 March 2020

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The activity of tissue factor pathway inhibitor in experimental models of superantigen-induced shock and polymicrobial intra-abdominal sepsis

31 March 2020

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Complete activation of autophagic process attenuates liver injury and improves survival in septic mice.

31 March 2020

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The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

31 March 2020

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Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis

31 March 2020

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Rolipram improves renal perfusion and function during sepsis in the mouse

31 March 2020

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Significant contribution of spleen cells in mediating the lethal effects of endotoxin in vivo

31 March 2020

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12 December 2020

Species differences in Kupffer cells and endotoxin sensitivity.

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12 December 2020

Ibuprofen improves survival from endotoxic shock in the rat.

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12 December 2020

E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators

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12 December 2020

Endogenous modulators of TNF and IL-1 response are under partial control of TNF in baboon bacteremia.

1 reference

12 December 2020

A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group

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12 December 2020

Prevention of death from endotoxin with antisera. I. The risk of fatal anaphylaxis to endotoxin.

1 reference

12 December 2020

Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. BN 52021 Sepsis Study Group.

1 reference

12 December 2020

The hidden cost of housing practices: using noninvasive imaging to quantify the metabolic demands of chronic cold stress of laboratory mice

1 reference

12 December 2020

Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group

1 reference

12 December 2020

An antagonist of platelet-activating factor suppresses endotoxin-induced tumor necrosis factor and mortality in mice pretreated with carrageenan.

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12 December 2020

Lethality for mice and chick embryos, pyrogenicity in rabbits and ability to gelate lysate from amoebocytes of Limulus polyphemus by lipopolysaccharides from Bacteroides, Fusobacterium and Veillonella

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12 December 2020

[Study of the tolerance of adrenalectomized mice using an endotoxin labeled with Cr-51.]

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12 December 2020

CP-0127, a novel potent bradykinin antagonist, increases survival in rat and rabbit models of endotoxin shock

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12 December 2020

Protection against lethal Escherichia coli bacteremia in baboons (Papio anubis) by pretreatment with a 55-kDa TNF receptor (CD120a)-Ig fusion protein, Ro 45-2081.

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12 December 2020

Accelerated apoptosis contributes to aging-related hyperinflammation in endotoxemia.

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12 December 2020

A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group

1 reference

12 December 2020

Treatment of severe systemic inflammatory response syndrome and sepsis with a novel bradykinin antagonist, deltibant (CP-0127). Results of a randomized, double-blind, placebo-controlled trial. CP-0127 SIRS and Sepsis Study Group

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12 December 2020

Pretreatment with troglitazone decreases lethality during endotoxemia in mice.

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12 December 2020

Effects of recombinant dimeric TNF receptor on human inflammatory responses following intravenous endotoxin administration

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12 December 2020

A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer

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12 December 2020

Identifiers

DOI

10.1038/NRD4368

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2 August 2017

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