Shedding metabo‘light’ on the search for sepsis biomarkers

Santos, Claudia C. dos

doi:10.1186/s13054-015-0969-7

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…In a previous study, nine infected neonates with early- and late-onset sepsis were distinguished from 16 controls after urine analysis by 1 H-NMR and GC-MS. However, these were only evaluated at one time-point, while no clarification was made as to whether they suffered clinical or blood culture proven sepsis17. On the basis of our results, urine metabolomics show potential as a diagnostic means, not only for the reliable detection of septic neonates, but also for monitoring response to therapy.…”

Section: Discussionmentioning

confidence: 96%

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Urine metabolomics in neonates with late-onset sepsis in a case-control study

Sarafidis

Chatziioannou

Thomaidou

et al. 2017

Sci Rep

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Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

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Section: Discussionmentioning

confidence: 96%

“…Overall, these investigations showed significant promise on disease profiling and biomarker identification in sepsis16. However, to date, relevant studies in neonatal sepsis are sparse17.…”

mentioning

confidence: 99%

Urine metabolomics in neonates with late-onset sepsis in a case-control study

Sarafidis

Chatziioannou

Thomaidou

et al. 2017

Sci Rep

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“…Recent studies have highlighted the potential prognostic role of metabolomics in sepsis patients [17][18][19]. Although promising, the existing literature of metabolomic studies on sepsis mortality prediction is limited by the use of individual cohorts with small sample sizes and low statistical power, as well as the use of varying analytical pipelines that can make it challenging to synthesize findings.…”

Section: Introductionmentioning

confidence: 99%

Prediction of sepsis mortality using metabolite biomarkers in the blood: a meta-analysis of death-related pathways and prospective validation

Wang

Sun

Teng

et al. 2020

BMC Med

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Background: Sepsis is a leading cause of death in intensive care units (ICUs), but outcomes of individual patients are difficult to predict. The recently developed clinical metabolomics has been recognized as a promising tool in the clinical practice of critical illness. The objective of this study was to identify the unique metabolic biomarkers and their pathways in the blood of sepsis nonsurvivors and to assess the prognostic value of these pathways. Methods: We searched PubMed, EMBASE, Cochrane, Web of Science, CNKI, Wangfang Data, and CQVIP from inception until July 2019. Eligible studies included the metabolomic analysis of blood samples from sepsis patients with the outcome. The metabolic pathway was assigned to each metabolite biomarker. The meta-analysis was performed using the pooled fold changes, area under the receiver operating characteristic curve (AUROC), and vote-counting of metabolic pathways. We also conducted a prospective cohort metabolomic study to validate the findings of our meta-analysis. Results: The meta-analysis included 21 cohorts reported in 16 studies with 2509 metabolite comparisons in the blood of 1287 individuals. We found highly limited overlap of the reported metabolite biomarkers across studies. However, these metabolites were enriched in several death-related metabolic pathways (DRMPs) including amino acids, mitochondrial metabolism, eicosanoids, and lysophospholipids. Prediction of sepsis death using DRMPs yielded a pooled AUROC of 0.81 (95% CI 0.76-0.87), which was similar to the combined metabolite biomarkers with a merged AUROC of 0.82 (95% CI 0.78-0.86) (P > 0.05). A prospective metabolomic analysis of 188 sepsis patients (134 survivors and 54 nonsurvivors) using the metabolites from DRMPs produced an AUROC of 0.88 (95% CI 0.78-0.97). The sensitivity and specificity for the prediction of sepsis death were 80.4% (95% CI 66.9-89.4%) and 78.8% (95% CI 62.3-89.3%), respectively. Conclusions: DRMP analysis minimizes the discrepancies of results obtained from different metabolomic methods and is more practical than blood metabolite biomarkers for sepsis mortality prediction. Trial registration: The meta-analysis was registered on OSF Registries, and the prospective cohort study was registered on the Chinese Clinical Trial Registry (ChiCTR1800015321).

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Serum concentrations of apoptosis-associated molecules in septic children with leukemia, neutropenia and fever

et al. 2017

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It has been shown that Fas, Fas-L, TNF and TNFR-1 display high serum concentrations in subjects with sepsis. This suggests that these are potential severity markers. However, the serum concentration of these molecules in children with leukemia and suspected sepsis has to be established before proposing their use as diagnostic biomarkers. We included children <17 years of age diagnosed with acute lymphoblastic leukemia with neutropenia and fever (NF). The subjects were divided into two groups: (1) leukemia and NF with sepsis, (2) leukemia and NF without sepsis. Determination of serum levels of TNF-α, TNFR-1, Fas and Fas-L was performed using ELISA tests, and apoptosis percentage using flow cytometry. Seventy-two subjects with ALL and NF were included in the two groups. The highest serum levels of TNF-α (35.2 ± 7.6 pg/ml) and TNF-R1 (4102 ± 2440) and the lowest levels of Fas-L (19.4 ± 7.3 pg/ml) were found in group 2: however, the difference in comparison with patients without sepsis was not statistically significant. Low levels of Fas-L and low percentage of apoptotic cells are observed in septic subjects. This pattern may reflect the presence of sepsis among subjects with NF secondary to leukemia.

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Shedding metabo‘light’ on the search for sepsis biomarkers

Cited by 5 publications

References 13 publications

Urine metabolomics in neonates with late-onset sepsis in a case-control study

Urine metabolomics in neonates with late-onset sepsis in a case-control study

Prediction of sepsis mortality using metabolite biomarkers in the blood: a meta-analysis of death-related pathways and prospective validation

Serum concentrations of apoptosis-associated molecules in septic children with leukemia, neutropenia and fever

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