Mass spectrometry for the discovery of biomarkers of sepsis

Ludwig, Katelyn R.; Hummon, Amanda B.

doi:10.1039/c6mb00656f

Cited by 77 publications

(76 citation statements)

References 128 publications

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“…The potential for the discovery of new biomarkers has increased through the use of proteomic and metabolomic techniques, particularly due to the advances made in mass spectrometry [135]. This approach has already been used to identify a panel of metabolites, described as a "biopattern", for the triage of paediatric patients with suspected sepsis [136].…”

Section: Identification Of New Biomarkers and Diagnostic Toolsmentioning

confidence: 99%

Biomarkers for Point-of-Care Diagnosis of Sepsis

2020

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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In 2017, almost 50 million cases of sepsis were recorded worldwide and 11 million sepsis-related deaths were reported. Therefore, sepsis is the focus of intense research to better understand the complexities of sepsis response, particularly the twin underlying concepts of an initial hyper-immune response and a counter-immunological state of immunosuppression triggered by an invading pathogen. Diagnosis of sepsis remains a significant challenge. Prompt diagnosis is essential so that treatment can be instigated as early as possible to ensure the best outcome, as delay in treatment is associated with higher mortality. In order to address this diagnostic problem, use of a panel of biomarkers has been proposed as, due to the complexity of the sepsis response, no single marker is sufficient. This review provides background on the current understanding of sepsis in terms of its epidemiology, the evolution of the definition of sepsis, pathobiology and diagnosis and management. Candidate biomarkers of interest and how current and developing point-of-care testing approaches could be used to measure such biomarkers is discussed.

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Section: Identification Of New Biomarkers and Diagnostic Toolsmentioning

confidence: 99%

Biomarkers for Point-of-Care Diagnosis of Sepsis

2020

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“…Metabolomics could reveal sepsis-related metabolic pathways, such as hypoxia, oxidative stress, and increased energy needs (influencing glucose levels and oxidative metabolism of fatty acids) [94,96].…”

Section: Metabolomics and Sepsismentioning

confidence: 99%

How could metabolomics change pediatric health?

Bardanzellu

Fanos

2020

Ital J Pediatr

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In the last years, 'omics' technologies, and especially metabolomics, emerged as expanding scientific disciplines and promising technologies in the characterization of several pathophysiological processes. In detail, metabolomics, able to detect in a dynamic way the whole set of molecules of low molecular weight in cells, tissues, organs, and biological fluids, can provide a detailed phenotypic portray, representing a metabolic "snapshot." Thanks to its numerous strength points, metabolomics could become a fundamental tool in human health, allowing the exact evaluation of individual metabolic responses to pathophysiological stimuli including drugs, environmental changes, lifestyle, a great number of diseases and other epigenetics factors. Moreover, if current metabolomics data will be confirmed on larger samples, such technology could become useful in the early diagnosis of diseases, maybe even before the clinical onset, allowing a clinical monitoring of disease progression and helping in performing the best therapeutic approach, potentially predicting the therapy response and avoiding overtreatments. Moreover, the application of metabolomics in nutrition could provide significant information on the best nutrition regimen, optimal infantile growth and even in the characterization and improvement of commercial products' composition. These are only some of the fields in which metabolomics was applied, in the perspective of a precision-based, personalized care of human health. In this review, we discuss the available literature on such topic and provide some evidence regarding clinical application of metabolomics in heart diseases, auditory disturbance, nephrouropathies, adult and pediatric cancer, obstetrics, perinatal conditions like asphyxia, neonatal nutrition, neonatal sepsis and even some neuropsychiatric disorders, including autism. Our research group has been interested in metabolomics since several years, performing a wide spectrum of experimental and clinical studies, including the first metabolomics analysis of human breast milk. In the future, it is reasonable to predict that the current knowledge could be applied in daily clinical practice, and that sensible metabolomics biomarkers could be easily detected through cheap and accurate sticks, evaluating biofluids at the patient's bed, improving diagnosis, management and prognosis of sick patients and allowing a personalized medicine. A dream? May be I am a dreamer, but I am not the only one.

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“…In the model proposed by Calvano et al [28], the inflammatory response is activated when endotoxin (lipopolysaccharide; LPS) is recognized by the Toll-like receptor 4 (TLR4), which stimulates complex signaling cascades and activates transcriptional factors (e.g. nuclear factor kappa-B (NF-κB) and activator protein 1 (AP-1)) [17,18,20,34,44]. This amplified signal activates the transcription of inflammatory genes.…”

Section: Numerical Modelmentioning

confidence: 99%

“…In the early stage of the disease, monocytes, macrophages and neutrophils activate the innate immune system, which correspond to increases in pro-inflammatory cytokines and chemokines, to help the fight against infection [11-13, 17, 18]. However, when extreme reactions occur, they can also lead to harmful failures of various organs [6,8,9,[11][12][13][17][18][19][20]. This response is balanced by negative feedback leading to the release of anti-inflammatory mediators, which protect against extreme inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, if early and aggressive treatments (appropriate antibiotherapy, fluid resuscitation) are applied, the prognosis is improved in the first hours of shock and many patients now survive after this critical step [6,14,17,18,[21][22][23][24][25][26]. However, a significant proportion of these patients enter an immunosuppressed stage and die after a delayed phase of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Mathematical modeling of septic shock: an innovative tool for assessing therapeutic hypotheses

et al. 2019

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Septic shock is provoked by hyper-activation of the pro-inflammatory response after infection and the patient requires anti-inflammatory treatment. However, the immune system develops a compensatory mechanism where the resulting feedback leads to an anti-inflammatory response after the initial state, which is referred to as immunodeficiency. Therefore, the initial therapeutic treatment with anti-inflammatory intervention has failed for almost 20 years and it has been changed in the last 10 years based on modulation of the inflammatory response. Using in silico methods, it is possible to develop a new approach based on physiopathology for treating septic shock. According to our new mathematical model, we can consider the dysfunctional immune system in a patient with septic shock and modify two parameters at different times to determine a possible treatment, and bearing out the single nucleoid polymorphism (SNP) may predominate the further deterioration of sepsis. The result represents the initial anti-inflammatory treatment with interleukin-10 activation and an increased risk of mortality over time for the septic shock patient, excluding the early stages. However, a hypothetical treatment based on interleukin-10 inhibition can change the patient's immune stage and provide a new therapy according to our results, and show that the frequency of pro-inflammatory related gene SNP can be the possibility of increase sepsis risk. In conclusion, our proposed in silico method can explore therapeutic strategies and predict their associated efficacy and important factors, with the ultimate objective of improving treatments to reduce mortality.

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Mass spectrometry for the discovery of biomarkers of sepsis

Cited by 77 publications

References 128 publications

Biomarkers for Point-of-Care Diagnosis of Sepsis

Biomarkers for Point-of-Care Diagnosis of Sepsis

How could metabolomics change pediatric health?

Mathematical modeling of septic shock: an innovative tool for assessing therapeutic hypotheses

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