The new sepsis consensus definitions (Sepsis-3): the good, the not-so-bad, and the actually-quite-pretty

Singer, Mervyn

doi:10.1007/s00134-016-4600-4

Cited by 61 publications

(46 citation statements)

References 15 publications

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“…Eight adult (> 18 years) septic shock patients, as defined by The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3) [ 18 ] were enrolled. All patients had to exhibit positive blood cultures or a defined focus of infection (e.g.…”

Section: Methodsmentioning

confidence: 99%

Para-hydroxyphenylpyruvate inhibits the pro-inflammatory stimulation of macrophage preventing LPS-mediated nitro-oxidative unbalance and immunometabolic shift

et al. 2017

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Targeting metabolism is emerging as a promising therapeutic strategy for modulation of the immune response in human diseases. In the presented study we used the lipopolysaccharide (LPS)-mediated activation of RAW 264.7 macrophage-like cell line as a model to investigate changes in the metabolic phenotype and to test the effect of p-hydroxyphenylpyruvate (pHPP) on it. pHPP is an intermediate of the PHE/TYR catabolic pathway, selected as analogue of the ethyl pyruvate (EP), which proved to exhibit antioxidant and anti-inflammatory activities. The results obtained show that LPS-priming of RAW 264.7 cell line to the activated M1 state resulted in up-regulation of the inducible nitric oxide synthase (iNOS) expression and consequently of NO production and in release of the pro-inflammatory cytokine IL-6. All these effects were prevented dose dependently by mM concentrations of pHPP more efficiently than EP. Respirometric and metabolic flux analysis of LPS-treated RAW 264.7 cells unveiled a marked metabolic shift consisting in downregulation of the mitochondrial oxidative phosphorylation and upregulation of aerobic glycolysis respectively. The observed respiratory failure in LPS-treated cells was accompanied with inhibition of the respiratory chain complexes I and IV and enhanced production of reactive oxygen species. Inhibition of the respiratory activity was also observed following incubation of human neonatal fibroblasts (NHDF-neo) with sera from septic patients. pHPP prevented all the observed metabolic alteration caused by LPS on RAW 264.7 or by septic sera on NHDF-neo. Moreover, we provide evidence that pHPP is an efficient reductant of cytochrome c. On the basis of the presented results a working model, linking pathogen-associated molecular patterns (PAMPs)-mediated immune response to mitochondrial oxidative metabolism, is put forward along with suggestions for its therapeutic control.

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Section: Methodsmentioning

confidence: 99%

Para-hydroxyphenylpyruvate inhibits the pro-inflammatory stimulation of macrophage preventing LPS-mediated nitro-oxidative unbalance and immunometabolic shift

et al. 2017

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“…The SIRS approach has been criticized a lot in the last decade, especially because often, persons with a simple respiratory infection already fulfill two criteria. In 2016, new definitions have been proposed in human medicine, which define sepsis as life-threatening organ failure caused by a dysregulated host response to infection (Singer, 2016). The sequential organ failure assessment score (SOFA) is the central concept, which evaluates breathing, circulation, liver and kidney function, coagulation and the neurological condition.…”

Section: Definitionsmentioning

confidence: 99%

Rationele antimicrobiële therapie voor sepsis bij runderen in het licht van de nieuwe wetgeving over kritisch belangrijke antibiotica

Pardon¹,

Deprez²

2018

Vlaams Diergeneeskundig Tijdschrift

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Sepsis is a life-threatening condition in cattle, as in humans. Successful sepsis treatment requires a fast initiation of antimicrobial therapy with a broad-spectrum, bactericidal drug, administered intravenously. However, the new legislation limits the use of critically important fluoroquinolones and cephalosporins in food animal medicine, drugs which are considered highly effective for sepsis treatment and were previously frequently used for this indication. This article aims at providing an overview of the current knowledge of sepsis in cattle to aid practitioners in adapting their decision making process to treat sepsis. Sepsis incidence in cattle is likely seriously underestimated. This disease is almost unexplored in cattle, which makes it particularly difficult to design species specific guidelines. Sepsis diagnosis by blood culture reaches sufficient accuracy with the current laboratory technology. When adapting this procedure to a field environment, difficulties might arise, and the availability of adapted incubators in veterinary laboratories may be limited. However, these difficulties are likely to be overcome. Severe sepsis and septic shock are likely the only indications where the ‘urgency’ criterion of the new legislation would apply, but it is important to realize that alternative antimicrobial treatments with possibly similar efficacy are available.

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“…However, infections can be difficult to confirm. Currently blood cultures processed with standard microbiologic techniques are considered as gold standard for diagnosing infection, but, variety of factors, including prior antibiotic therapy could affect the diagnostic value of blood culture [3]. Bacteremia is identified in only about 30% of patients [4].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Utility of Presepsin and Procalcitonin in Critically Ill Patients With Suspected Sepsis: Comparison With Recent Clinical Criteria of Sepsis-3

Alikiaie

Mousavi

Nasri

2019

IJMBS

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Background: In this study, we aimed to investigate the diagnostic and prognostic utilities of presepsin and procalcitonin (PCT) in critically ill patients with suspected sepsis, for whom sepsis was diagnosed clinically based on the Survival Sepsis Campaign (SSC) criteria and to compare it with recent criteria of Sepsis-3. Methods: Blood samples for biomarker measurements of presepsin and PCT were drawn on days 1, 3 and 7 of ICU admission in a total of 26 patients. All patients were followed-up until death or discharge. All studied biomarkers were analyzed according to the diagnosis and severity of sepsis and for prognosis (all-cause mortality) at days 1, 3 and 7. Agreement between the diagnosis of clinical sepsis and presepsin or PCT-based sepsis was assessed using Cohen’s kappa Results: Clinical sepsis (based on Sepsis-3) and presepsin or PCT-based sepsis showed poor agreement (Kappa<0.4). Presepsin levels at day1 correlated significantly with mortality (r=0.45, P; 0.02). The diagnostic value of both presepsin and PCT to diagnose sepsis was weak (Area under curve (AUC) <0.75). The overall agreement in sepsis diagnosis was fair to good based on the both clinical criteria (P<0.05, Kappa: 0.5-0.75). More than 80% of patients (N=21) had sepsis based on presepsin upon admission. Both clinical criteria predicated that less than 20% of patients (N=5) had sepsis upon admission. Conclusion: Based on our findings, the overall agreement between the diagnosis of clinical sepsis and presepsin or PCT-based sepsis was poor. Also, our results show that the new Sepsis-3 definitions were accurate and equal to the previous definition of SSC guideline. Although, availability of diagnostic assays is variable in Iran, but, it seems that addition of developing decision tools that utilize biomarkers to help aid the rapid diagnosis of sepsis is necessary and may improve patient outcomes. Keywords: Presepsin, Pro Calcitonin, Sepsis, Diagnosis

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The new sepsis consensus definitions (Sepsis-3): the good, the not-so-bad, and the actually-quite-pretty

Cited by 61 publications

References 15 publications

Para-hydroxyphenylpyruvate inhibits the pro-inflammatory stimulation of macrophage preventing LPS-mediated nitro-oxidative unbalance and immunometabolic shift

Para-hydroxyphenylpyruvate inhibits the pro-inflammatory stimulation of macrophage preventing LPS-mediated nitro-oxidative unbalance and immunometabolic shift

Rationele antimicrobiële therapie voor sepsis bij runderen in het licht van de nieuwe wetgeving over kritisch belangrijke antibiotica

Diagnostic Utility of Presepsin and Procalcitonin in Critically Ill Patients With Suspected Sepsis: Comparison With Recent Clinical Criteria of Sepsis-3

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