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Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit.

Mickiewicz B, Tam P, Jenne CN, Leger C, Wong J, Winston BW, Doig C, Kubes P, Vogel HJ, Alberta Sepsis Netwo - Crit Care (2015)

Bottom Line: Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients.The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits.By using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality.

View Article: PubMed Central - PubMed

Affiliation: Bio-NMR-Centre, Department of Biological Sciences, University of Calgary, 2500 University Drive Northwest, Calgary, AB, T2N 1N4, Canada. bmmickie@ucalgary.ca.

ABSTRACT

Introduction: Septic shock is a major life-threatening condition in critically ill patients and it is well known that early recognition of septic shock and expedient initiation of appropriate treatment improves patient outcome. Unfortunately, to date no single compound has shown sufficient sensitivity and specificity to be used as a routine biomarker for early diagnosis and prognosis of septic shock in the intensive care unit (ICU). Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients. In this study, we have evaluated whether a combined nuclear magnetic resonance spectroscopy-based metabolomics and a multiplex cytokine/chemokine profiling approach could be used for diagnosis and prognostic evaluation of septic shock patients in the ICU.

Methods: Serum and plasma samples were collected from septic shock patients and ICU controls (ICU patients with the systemic inflammatory response syndrome but not suspected of having an infection). (1)H Nuclear magnetic resonance spectra were analyzed and quantified using the targeted profiling methodology. The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits.

Results: By using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality. These metabolites and cytokines/chemokines represent candidate biomarkers of the human response to septic shock and have the potential to improve early diagnosis and prognosis of septic shock.

Conclusions: Our findings show that integration of quantitative metabolic and inflammatory mediator data can be utilized for the diagnosis and prognosis of septic shock in the ICU.

No MeSH data available.


Related in: MedlinePlus

The OPLS-DA regression coefficient plot. Positive values of coefficients (the upper part of the diagram) indicate increased metabolite and cytokine/chemokine concentrations in the septic shock samples (fold change >1) while negative values (the lower part of diagram) present a decrease in metabolite and cytokine/chemokine concentrations, as compared to ICU controls (fold change <1). Only significant metabolites and cytokines/chemokines are shown (P <0.05, two-sample t test). ICU, intensive care unit; OPLS-DA, orthogonal partial least squares discriminant analysis.
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Fig3: The OPLS-DA regression coefficient plot. Positive values of coefficients (the upper part of the diagram) indicate increased metabolite and cytokine/chemokine concentrations in the septic shock samples (fold change >1) while negative values (the lower part of diagram) present a decrease in metabolite and cytokine/chemokine concentrations, as compared to ICU controls (fold change <1). Only significant metabolites and cytokines/chemokines are shown (P <0.05, two-sample t test). ICU, intensive care unit; OPLS-DA, orthogonal partial least squares discriminant analysis.

Mentions: As shown in Figure 3, fifteen metabolites and eight inflammatory mediators contribute significantly to the separation between septic shock samples and ICU controls. Eight metabolites revealed altered concentrations in septic shock patients (phenylalanine, myo-inositol, isobutyrate, 3-hydroxybutyrate, urea, O-acetylcarnitine, 2-hydroxybutyrate and proline) while the concentrations of propylene glycol, threonine, valine, arginine, glutamate, methanol and glucose were decreased. Septic shock patients showed also high levels of interferon-inducible protein-10 (IP-10), hepatocyte growth factor (HGF), interleukin-18 (IL-18), IL-1 and IL-2 receptor antagonists (IL-1Ra, IL-2Ra) and decreased concentrations of IL-1α, monocyte-specific chemokine 3 (MCP-3) and tumor necrosis factor beta (TNF-β).Figure 3


Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit.

Mickiewicz B, Tam P, Jenne CN, Leger C, Wong J, Winston BW, Doig C, Kubes P, Vogel HJ, Alberta Sepsis Netwo - Crit Care (2015)

The OPLS-DA regression coefficient plot. Positive values of coefficients (the upper part of the diagram) indicate increased metabolite and cytokine/chemokine concentrations in the septic shock samples (fold change >1) while negative values (the lower part of diagram) present a decrease in metabolite and cytokine/chemokine concentrations, as compared to ICU controls (fold change <1). Only significant metabolites and cytokines/chemokines are shown (P <0.05, two-sample t test). ICU, intensive care unit; OPLS-DA, orthogonal partial least squares discriminant analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4340832&req=5

Fig3: The OPLS-DA regression coefficient plot. Positive values of coefficients (the upper part of the diagram) indicate increased metabolite and cytokine/chemokine concentrations in the septic shock samples (fold change >1) while negative values (the lower part of diagram) present a decrease in metabolite and cytokine/chemokine concentrations, as compared to ICU controls (fold change <1). Only significant metabolites and cytokines/chemokines are shown (P <0.05, two-sample t test). ICU, intensive care unit; OPLS-DA, orthogonal partial least squares discriminant analysis.
Mentions: As shown in Figure 3, fifteen metabolites and eight inflammatory mediators contribute significantly to the separation between septic shock samples and ICU controls. Eight metabolites revealed altered concentrations in septic shock patients (phenylalanine, myo-inositol, isobutyrate, 3-hydroxybutyrate, urea, O-acetylcarnitine, 2-hydroxybutyrate and proline) while the concentrations of propylene glycol, threonine, valine, arginine, glutamate, methanol and glucose were decreased. Septic shock patients showed also high levels of interferon-inducible protein-10 (IP-10), hepatocyte growth factor (HGF), interleukin-18 (IL-18), IL-1 and IL-2 receptor antagonists (IL-1Ra, IL-2Ra) and decreased concentrations of IL-1α, monocyte-specific chemokine 3 (MCP-3) and tumor necrosis factor beta (TNF-β).Figure 3

Bottom Line: Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients.The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits.By using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality.

View Article: PubMed Central - PubMed

Affiliation: Bio-NMR-Centre, Department of Biological Sciences, University of Calgary, 2500 University Drive Northwest, Calgary, AB, T2N 1N4, Canada. bmmickie@ucalgary.ca.

ABSTRACT

Introduction: Septic shock is a major life-threatening condition in critically ill patients and it is well known that early recognition of septic shock and expedient initiation of appropriate treatment improves patient outcome. Unfortunately, to date no single compound has shown sufficient sensitivity and specificity to be used as a routine biomarker for early diagnosis and prognosis of septic shock in the intensive care unit (ICU). Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients. In this study, we have evaluated whether a combined nuclear magnetic resonance spectroscopy-based metabolomics and a multiplex cytokine/chemokine profiling approach could be used for diagnosis and prognostic evaluation of septic shock patients in the ICU.

Methods: Serum and plasma samples were collected from septic shock patients and ICU controls (ICU patients with the systemic inflammatory response syndrome but not suspected of having an infection). (1)H Nuclear magnetic resonance spectra were analyzed and quantified using the targeted profiling methodology. The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits.

Results: By using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality. These metabolites and cytokines/chemokines represent candidate biomarkers of the human response to septic shock and have the potential to improve early diagnosis and prognosis of septic shock.

Conclusions: Our findings show that integration of quantitative metabolic and inflammatory mediator data can be utilized for the diagnosis and prognosis of septic shock in the ICU.

No MeSH data available.


Related in: MedlinePlus