Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino‐Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children

Spanaki, Anna Maria; Tavladaki, Theonymfi; Dimitriou, Helen; Kozlov, Andrey V.; Duvigneau, J. Catharina; Meleti, E.; Weidinger, Adelheid; Papakonstantinou, Evangelos; Briassoulis, George

doi:10.1002/jpen.1050

Cited by 27 publications

(20 citation statements)

References 38 publications

(41 reference statements)

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“…It is the first time that survivin-WT gene or protein expression, as well as total caspases, including active and cleaved forms, are shown to be overexpressed in sepsis and that survivin-ΔEx3, -WT, along with caspase-9 and survivin protein, could better discriminate sepsis among critically ill patients. This finding further enhances results of recent studies, showing that biomolecules, related to repressed bioenergetics and innate immunity 50 , hypo-metabolism and acute hormonal stress 51 , could better discriminate sepsis from SIRS, compared to CRP or lactate.…”

Section: Discussionsupporting

confidence: 84%

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

Miliaraki

Briassoulis

Ilia

et al. 2021

Sci Rep

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Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases’ responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.

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Section: Discussionsupporting

confidence: 84%

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

Miliaraki

Briassoulis

Ilia

et al. 2021

Sci Rep

Self Cite

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“…Fifth, because the serum concentrations of CRP and albumin were only analyzed at ICU admission, we could not evaluate the changes in CRP, albumin, and CRP/albumin ratio over time. Spanaki et al reported that CRP decreases longitudinally among ICU survivors whereas SIRS survivors showed a longitudinal decline in albumin [ 37 ]. Further studies that investigate the changes in these markers are needed in the future.…”

Section: Discussionmentioning

confidence: 99%

The C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Critically Ill Patients

Park

Chung

Song

et al. 2018

JCM

129

113

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The C-reactive protein (CRP)/albumin ratio has recently emerged as a marker for poor prognosis or mortality across various patient groups. This study aimed to identify the association between CRP/albumin ratio and 28-day mortality and predict the accuracy of CRP/albumin ratio for 28-day mortality in medical intensive care unit (ICU) patients. This was a retrospective cohort study of 875 patients. We evaluated the prognostic value of CRP/albumin ratio to predict mortality at 28 days after ICU admission, using Cox proportional hazard model and Kaplan-Meier survival analysis. The 28-day mortality was 28.0%. In the univariate analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p < 0.001), CRP level (p = 0.045), albumin level (p < 0.001), and CRP/albumin ratio (p = 0.032) were related to 28-day mortality. The area under the receiver operating characteristic (ROC) curve (the area under the ROC curves (AUC)) of CRP/albumin ratio was higher than that of CRP for mortality (0.594 vs. 0.567, p < 0.001). The cut-off point for CRP/albumin ratio for mortality was 34.3. On Cox proportional-hazard regression analysis, APACHE II score (hazards ratio (HR) = 1.05, 95% confidence interval (CI) = 1.04–1.07, p < 0.001) and CRP/albumin ratio (HR = 1.68, 95% CI = 1.27–2.21, p < 0.001 for high CRP/albumin ratio) were independent predictors of 28-day mortality. Higher CRP/albumin ratio was associated with increased mortality in critically ill patients.

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“…Other potential protective effects of heme oxygenase induction are a direct modulation of antioxidant genes transcription, an increased production of the tissue mediator carbon monoxide and a decrease in cellular prooxidant heme (42). Bilirubin might also reduce cellular damage through biliverdin reductase action, which has recently been documented to be increased in septic patients (47). Indeed, when bilirubin reacts with reactive oxygen species, toxicity is neutralized and bilirubin is oxidized to biliverdin.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, when bilirubin reacts with reactive oxygen species, toxicity is neutralized and bilirubin is oxidized to biliverdin. Biliverdin can be converted back to bilirubin through biliverdin reductase, and by repeating this cycle, the antioxidative and cytoprotective effect of small amounts of bilirubin is greatly amplified (44, 47). In our study, however, total plasma bilirubin concentrations on the first day of critical illness were associated with PICU mortality in a “U-shape” relationship, in which both low and high levels of bilirubin were associated with higher risk of death.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Prognostic Value of Abnormal Liver Test Results in Critically Ill Children and the Impact of Delaying Parenteral Nutrition*

Jenniskens

Güiza

Haghedooren

et al. 2018

Pediatric Critical Care Medicine

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Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino‐Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children

Cited by 27 publications

References 38 publications

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

The C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Critically Ill Patients

Prevalence and Prognostic Value of Abnormal Liver Test Results in Critically Ill Children and the Impact of Delaying Parenteral Nutrition*

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