Science, medicine, and the future: Pathogenesis of sepsis: new concepts and implications for future treatment

Bochud, Pierre–Yves

doi:10.1136/bmj.326.7383.262

Cited by 195 publications

(147 citation statements)

References 30 publications

(23 reference statements)

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“…[5][6][7] Over the last 3 decades, numerous trials have failed to demonstrate that blocking specific inflammatory mediators is beneficial in sepsis. 5,6 Given the acute onset and unpredictable nature of sepsis, primary prevention was never attempted in the management of this syndrome.…”

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confidence: 99%

“…1 It is generally accepted that sepsis syndrome reflects the delicate balance between extensive triggering of defense mechanisms by invading microorganisms and both direct and indirect effects of these microorganisms and their products. 4,5 Most investigators would agree that sepsis and the systemic inflammatory response syndrome are accompanied by the inability to regulate the inflammatory response and that the cause of this perturbation is still unknown. [5][6][7] Over the last 3 decades, numerous trials have failed to demonstrate that blocking specific inflammatory mediators is beneficial in sepsis.…”

mentioning

confidence: 99%

“…4,5 Most investigators would agree that sepsis and the systemic inflammatory response syndrome are accompanied by the inability to regulate the inflammatory response and that the cause of this perturbation is still unknown. [5][6][7] Over the last 3 decades, numerous trials have failed to demonstrate that blocking specific inflammatory mediators is beneficial in sepsis. 5,6 Given the acute onset and unpredictable nature of sepsis, primary prevention was never attempted in the management of this syndrome.…”

mentioning

confidence: 99%

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Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis

et al. 2004

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confidence: 99%

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Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis

et al. 2004

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“…This medical condition often results in intractable hypotension, which is a significant cause of death for patients in intensive care units (2). Host factors associated with multiorgan dysfunction include increased levels of proinflammatory cytokines such as TNF-␣, IL-1␤, IL-6, and IL-8 (3), and glycerophospholipids (4) such as platelet-activating factor (PAF).…”

mentioning

confidence: 99%

Lipoteichoic Acid-Induced Nitric Oxide Production Depends on the Activation of Platelet-Activating Factor Receptor and Jak2

Han

Kim

Seo

et al. 2006

The Journal of Immunology

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NO production by macrophages in response to lipoteichoic acid (LTA) and a synthetic lipopeptide (Pam3CSK4) was investigated. LTA and Pam3CSK4 induced the production of both TNF-α and NO. Inhibitors of platelet-activating factor receptor (PAFR) blocked LTA- or Pam3CSK4-induced production of NO but not TNF-α. Jak2 tyrosine kinase inhibition blocked LTA-induced production of NO but not TNF-α. PAFR inhibition blocked phosphorylation of Jak2 and STAT1, a key factor for expressing inducible NO synthase. In addition, LTA did not induce IFN-β expression, and p38 mitogen-activated protein serine kinase was necessary for LTA-induced NO production but not for TNF-α production. These findings suggest that Gram-positive bacteria induce NO production using a PAFR signaling pathway to activate STAT1 via Jak2. This PAFR/Jak2/STAT1 signaling pathway resembles the IFN-β, type I IFNR/Jak/STAT1 pathway described for LPS. Consequently, Gram-positive and Gram-negative bacteria appear to have different but analogous mechanisms for NO production.

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“…It also increases hospital stay and cost (1). Patients with fever, leukocytosis, increased heart rate and respiratory rate with suspected or proven infection can be diagnosed with sepsis.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Diagnostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor in Sepsis

Barati

Shekarabi

Chobkar

et al. 2014

Arch Clin Infect Dis

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Background: Sepsis is one of the most important causes of morbidity and mortality in the intensive care units (ICUs). It is difficult to accurately differentiate sepsis from similar diseases rapidly. Therefore, it becomes critical to identify any biomarker with the ability of differentiation between sepsis and nonsepsis conditions. The urokinase plasminogen activator receptor has been implicated as an important factor in regulation of leukocyte adhesion and migration. Objectives: In this study, we evaluated the value of soluble urokinase plasminogen activator receptor (suPAR), erythrocyte sedimentation (ESR), and C-reactive protein (CRP) serum levels in terms of their value for sepsis diagnosis in ICU patients. Patients and Methods:We enrolled 107 ICU patients; 40 with sepsis, 43 with systemic inflammatory response syndrome, and 24 as control group. Serum soluble urokinase plasminogen activator receptor, ESR, white blood cell (WBC), and CRP levels were measured on the day of admission. Results: The group with sepsis had higher suPAR, ESR, and CRP levels compared with the group with noninfectious systemic inflammatory response syndrome (SIRS) (P = 0.01, 0.00 and 0.00, respectively). CRP concentrations and ESR were higher in the sepsis group than in the non-SIRS group (P = 0.00 and 0.00, respectively). In a receiver-operating characteristic curve analysis, ESR, CRP and suPAR had an area under the curve larger than 0.65 (P = 0.00) in distinguishing between septic and noninfectious SIRS patients. CRP, ESR and suPAR had a sensitivity of 87%, 71% and 66% and a specificity of 59%, 76% and 74% respectively in diagnosing infection in SIRS. Conclusions:The diagnostic values of CRP and ESR were better than suPAR and WBC count in patients with sepsis.

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Science, medicine, and the future: Pathogenesis of sepsis: new concepts and implications for future treatment

Cited by 195 publications

References 30 publications

Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis

Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis

Lipoteichoic Acid-Induced Nitric Oxide Production Depends on the Activation of Platelet-Activating Factor Receptor and Jak2

Evaluation of Diagnostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor in Sepsis

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