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

Nadel, Simon; Goldstein, Brahm; Williams, Mark D.; Dalton, Heidi J.; Peters, Mark; Macias, William L.; Abd-Allah, Shamel; Levy, Howard; Angle, Robinette; Wang, Dazhe; Sundin, David P.; Giroir, Brett P.

doi:10.1016/s0140-6736(07)60411-5

Cited by 452 publications

(248 citation statements)

References 16 publications

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“…3D). These findings provide strong support for an anti-TLR4 treatment strategy in patients with fulminant meningococcemia associated with high levels of circulating endotoxin in whom anti-LPS (i.e., recombinant bactericidal/permeability-increasing protein) and anti-sepsis (i.e., activated protein C) therapies have failed (24,25). Unlike monoclonal antibodies raised against TLR4-MD-2, which work only when administered prophylactically in bacterial sepsis (26,27), anti-TLR4 antibodies afforded remarkable protection against lethal E. coli sepsis when treatment was delayed for as much as 13 h after the onset of infection (Fig.…”

Section: Discussionmentioning

confidence: 72%

Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4

Roger

Froidevaux

Roy

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

251

192

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Toll-like receptor 4 (TLR4), the signal-transducing molecule of the LPS receptor complex, plays a fundamental role in the sensing of LPS from Gram-negative bacteria. Activation of TLR4 signaling pathways by LPS is a critical upstream event in the pathogenesis of Gram-negative sepsis, making TLR4 an attractive target for novel antisepsis therapy. To validate the concept of TLR4-targeted treatment strategies in Gram-negative sepsis, we first showed that TLR4 ؊/؊ and myeloid differentiation primary response gene 88 (MyD88) ؊/؊ mice were fully resistant to Escherichia coli-induced septic shock, whereas TLR2 ؊/؊ and wild-type mice rapidly died of fulminant sepsis. Neutralizing anti-TLR4 antibodies were then generated using a soluble chimeric fusion protein composed of the N-terminal domain of mouse TLR4 (amino acids 1-334) and the Fc portion of human IgG1. Anti-TLR4 antibodies inhibited intracellular signaling, markedly reduced cytokine production, and protected mice from lethal endotoxic shock and E. coli sepsis when administered in a prophylactic and therapeutic manner up to 13 h after the onset of bacterial sepsis. These experimental data provide strong support for the concept of TLR4-targeted therapy for Gram-negative sepsis.endotoxic shock ͉ Gram-negative bacteria ͉ lipopolysaccharide ͉ TLR4

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Section: Discussionmentioning

confidence: 72%

Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4

Roger

Froidevaux

Roy

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

251

192

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“…Recombinant human activated protein C (rhAPC) has maybe been the most promising candidate for mediator directed therapy in sepsis, but clinical trials have not been able to provide sufficient evidence to justify general use of rhAPC in sepsis (117)(118)(119). Present guidelines recommend use of rhAPC in adult patients with high risk of death (113).…”

Section: Treatmentmentioning

confidence: 99%

Candidate inhibitors of porcine complement

Thorgersen¹,

Ghebremariam²,

Thurman³

et al. 2007

Molecular Immunology

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“…The sepsis‐related mortality rate in children is over 15% in patients with severe sepsis cases and even higher in septic shock,449, 450, 451 according to reports published as of 2012. The Surviving Sepsis Campaign Guidelines (SSCG) 2012 edition includes recommendations pertaining to child patients as “Pediatric Considerations” 29.…”

Section: Introductionmentioning

confidence: 99%

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

Nishida

Ogura

Egi

et al. 2018

Acute Medicine & Surgery

157

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Background and PurposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two‐thirds (>66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J‐SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta‐analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese‐specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non‐specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

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

Cited by 452 publications

References 16 publications

Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4

Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4

Candidate inhibitors of porcine complement

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

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