Biomarkers in Pediatric Sepsis: A Review of Recent Literature

Oikonomakou, Mariza Z; Gkentzi, Despoina; Gogos, Charalambos; Akinosoglou, Karolina

doi:10.2217/bmm-2020-0016

Cited by 22 publications

(22 citation statements)

References 196 publications

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“…Finally, although restricting the features used for phenotyping modeling to those available in routine clinical practice is reasonable, studies indicate that additional evidence such as advanced biomarkers driven by genomics may contribute in pediatric sepsis phenotyping. 52 , 53 A more optimized pediatric set of features should be pursued in future studies.…”

Section: Resultsmentioning

confidence: 99%

Pediatric sepsis phenotypes for enhanced therapeutics: An application of clustering to electronic health records

Koutroulis

Velez

Wang³

et al. 2022

JACEP Open

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Objective The heterogeneity of pediatric sepsis patients suggests the potential benefits of clustering analytics to derive phenotypes with distinct host response patterns that may help guide personalized therapeutics. We evaluate the relative performance of latent class analysis (LCA) and K‐means, 2 commonly used clustering methods toward the derivation of clinically useful pediatric sepsis phenotypes. Methods Data were extracted from anonymized medical records of 6446 pediatric patients that presented to 1 of 6 emergency departments (EDs) between 2013 and 2018 and were thereafter admitted. Using International Classification of Diseases (ICD)‐9 and ICD‐10 discharge codes, 151 patients were identified with a sepsis continuum diagnosis that included septicemia, sepsis, severe sepsis, and septic shock. Using feature sets used in related clustering studies, LCA and K‐means algorithms were used to derive 4 distinct phenotypic pediatric sepsis segmentations. Each segmentation was evaluated for phenotypic homogeneity, separation, and clinical use. Results Using the 2 feature sets, LCA clustering resulted in 2 similar segmentations of 4 clinically distinct phenotypes, while K‐means clustering resulted in segmentations of 3 and 4 phenotypes. All 4 segmentations identified at least 1 high severity phenotype, but LCA‐identified phenotypes reflected superior stratification, high entropy approaching 1 (eg, 0.994) indicating excellent separation between estimated phenotypes, and differential treatment/treatment response, and outcomes that were non‐randomly distributed across phenotypes ( P < 0.001). Conclusion Compared to K‐means, which is commonly used in clustering studies, LCA appears to be a more robust, clinically useful statistical tool in analyzing a heterogeneous pediatric sepsis cohort toward informing targeted therapies. Additional prospective studies are needed to validate clinical utility of predictive models that target derived pediatric sepsis phenotypes in emergency department settings.

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Section: Resultsmentioning

confidence: 99%

Pediatric sepsis phenotypes for enhanced therapeutics: An application of clustering to electronic health records

Koutroulis

Velez

Wang³

et al. 2022

JACEP Open

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“…Most are concerned with the use of CRP and PCT. However, there are also studies on biomarkers, such as different oxidative stress markers, cytokines/chemokines, and cell bioproducts 19…”

Section: Discussionmentioning

confidence: 99%

“…However, there are also studies on biomarkers, such as different oxidative stress markers, cytokines/chemokines, and cell bioproducts. 19 The studies on oxidative status in childhood sepsis are very limited. In a study by Molina et al, 20 it was found that the TAC, glutathione peroxidase activity, and plasmatic F2-isoprostanes concentrations were higher in both nonsevere and severe sepsis, whereas the erythrocyte thiol index, superoxide dismutase, and catalase activities were lower than those in the controls.…”

Section: Discussionmentioning

confidence: 99%

Clinical Utility of Total Oxidative Stress and Total Antioxidant Capacity in Childhood Febrile Neutropenia

Kara

Akyürek²,

Akbas

et al. 2021

Journal of Pediatric Hematology/Oncology

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The aim is to determine the oxidative status of children with febrile neutropenia (FEN). Blood samples were collected to determine the total antioxidant capacity (TAC) and total oxidative status (TOS) of healthy children (once) and children with FEN after 0, 48, and 96 hours. Eighteen patients with FEN were evaluated. The baseline TAC level of patients was significantly higher than that of the controls (P<0.0001). The TAC levels of patients with FEN with and without antibiotic modification were higher than those of the controls (P=0.002 and 0.02, respectively). The TAC levels of the patients with FEN with antibiotic modification were lower than those of the patients without antibiotic modification (P=0.0224). The oxidative stress index (OSI), calculated TOS/TAS, value of the children with FEN was lower than that of the controls (P<0.0001). The OSI values of the patients with FEN with and without antibiotic modification were lower than those of the control group (P=0.001 and <0.0001, respectively). The TAC values of the patients with antibiotic modification were higher than those of the patients without antibiotic modification (P=0.02). In conclusion, the oxidative status of the children with FEN was affected, and it can give information about the follow-up of FEN.

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“…Many of them have been proposed as possible biomarkers in preclinical or clinical studies, but no gold standard has been identi ed in pediatric patients, and studies are still relatively scarce (8, 20-24). It seems unlikely that one single molecule could be used as an optimal biomarker for the diagnosis and management of SBI (20,25,26). To date, no new candidate biomarker (including cytokine/chemokine, cell surface receptors, coagulation and complement molecules, markers of vasodilation or organ disfunction) has established to be more e cient than those already used in the clinical practice (CRP, PCT and WBC, ANC/WBC and the ratio of immature to total number of neutrophils), although some evidence is emerging about some new biomarkers (27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Candidate Biomarkers for the Detection of Serious Infections in Children: A Prospective Clinical Study

Pellegrin¹,

Penco²,

Amadio³

et al. 2020

Preprint

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BACKGROUND: Serious bacterial infections (SBI) in children are still associated with considerable morbidity and mortality. Early identification of SBI in children presenting with fever and/or signs of systemic inflammatory response (SIRS) remains challenging, as clinical presentation may be subtle, and the role of laboratory markers is still debated. The purpose of the present study is to evaluate the diagnostic role of established and candidate blood biomarkers for the early discrimination of SBI in pediatric patients presenting with fever and/or SIRS criteria.METHODS: Children who met SIRS criteria and had the clinical indication to perform blood sampling at the first medical evaluation were consecutively enrolled. A panel of biomarkers was performed at enrolment, including C-reactive protein, procalcitonin, white blood cell count (WBC), absolute neutrophil count (ANC), interleukin (IL)-6, IL-8, IL-10, human terminal complement complex (C5b-9), Plasmalemma-Vesicle-associated protein 1 (PV-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Phospholipase A2 (PLA2). Bivariate logistic regression models were created to identify significant predictors of SBI. RESULTS: Among 103 patients (median age 2.9 years, 60% males), 39 had a diagnosis of SBI (38%). Significant predictors of SBI were CRP (p=0.001) and ICAM-1 (p=0.043). In the subgroup of patients who were not immunocompromised because of a pre-existing medical condition or therapy (e.g. children with cancer and chemotherapy-induced neutropenia), significant predictors of SBI, were CRP (p=0.001) and ICAM-1 (p=0.037), WBC (p=0.035), ANC (p=0.012) and ANC/WBC ratio (p=0.015). The diagnostic performance of each variable as evaluated by means of ROC curves revealed suboptimal performance for all variables. A model combining CRP and ANC/WBC ratio, however, had a greater diagnostic accuracy than each one of the two variables. CONCLUSION: This study confirmed the limited usefulness of blood biomarkers for early diagnosis of SBI. WBC, ANC, ANC/WBC ratio, CRP and ICAM-1 showed the best, albeit moderate, diagnostic accuracy as single marker. At present, clinical judgement remains the mainstay for the diagnosis of SBIs in children.

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Biomarkers in Pediatric Sepsis: A Review of Recent Literature

Cited by 22 publications

References 196 publications

Pediatric sepsis phenotypes for enhanced therapeutics: An application of clustering to electronic health records

Pediatric sepsis phenotypes for enhanced therapeutics: An application of clustering to electronic health records

Clinical Utility of Total Oxidative Stress and Total Antioxidant Capacity in Childhood Febrile Neutropenia

Candidate Biomarkers for the Detection of Serious Infections in Children: A Prospective Clinical Study

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