Which biomarkers reveal neonatal sepsis?
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ABSTRACT:
SUBMITTER: Wang K
PROVIDER: S-EPMC3867385 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Publications
Which biomarkers reveal neonatal sepsis?
Wang Kun K Bhandari Vineet V Chepustanova Sofya S Huber Greg G O'Hara Stephen S O'Hern Corey S CS Shattuck Mark D MD Kirby Michael M
PloS one 20131218 12
We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA) and sparse support vector machine (SSVM) classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU). CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. Th ...[more]
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Project description:Neonatal sepsis continues to be a major cause of morbidity and mortality in India. To aid the diagnosis several direct and indirect methods are available. Sepsis screen has resulted in decrease in indiscriminate use of antibiotics. C-reactive protein can be easily estimated and is a useful indicator for favourable outcome or complication. The bacterial flora causing sepsis has changed over the years. Antimicrobial chemotherapy should be based on the prevalent organisms in the neonatal ICU. Outcome can be improved by judicious use of newer antibiotics and exchange transfusion when indicated.
| S-EPMC5531238 | biostudies-other
Project description:BackgroundPrognostic biomarker research neonatal sepsis is lacking. We assessed the utility of a validated pediatric prognostic tool called PERSEVERE II that uses decision tree methodology to predict mortality at discharge in neonates who experienced sepsis.MethodsProspective study in a dual-center cohort of neonates with sepsis admitted between June 2020 and December 2021. Biomarker analysis was done on serum samples obtained at the time of evaluation for the event.ResultsIn a cohort of 59 neonates with a mortality rate of 15.3%, PERSEVERE II was 67% sensitive and 59% specific for mortality, p 0.27. Amongst PERSEVERE II biomarkers, IL-8 showed good prognostic performance for mortality prediction with a cutoff of 300 pg/mL (sensitivity 100%, specificity 65%, negative predictive value 100%, AUC 0.87, p 0.0003). We derived a new decision tree that is neonate specific (nPERSEVERE) with improved performance compared to IL-8 (sensitivity 100%, specificity 86%, negative predictive value 100%, AUC 0.95, p < 0.0001).ConclusionsIL-8 and nPERSEVERE demonstrated good prognostic performance in a small cohort of neonates with sepsis. Moving toward precision medicine in sepsis, our study proposes an important tool for clinical trial prognostic enrichment that needs to be validated in larger studies.ImpactPrognostic and predictive biomarker research is lacking in the newborn intensive care unit. Biomarkers can be used at the time of evaluation for neonatal sepsis (blood culture acquisition) to identify neonates with high baseline mortality risk. Stratification is an important step toward precision medicine in neonatal sepsis.
| S-EPMC10261505 | biostudies-literature
Project description:Purpose of Review:Neonatal sepsis is a diagnosis made in infants less than 28 days of life and consists of a clinical syndrome that may include systemic signs of infection, circulatory shock, and multisystem organ failure. Recent Findings:Commonly involved bacteria include Staphylococcus aureus and Escherichia coli. Risk factors include central venous catheter use and prolonged hospitalization. Neonates are at significant risk of delayed recognition of sepsis until more ominous clinical findings and vital sign abnormalities develop. Blood culture remains the gold standard for diagnosis. Summary:Neonatal sepsis remains an important diagnosis requiring a high index of suspicion. Immediate treatment with antibiotics is imperative.
| S-EPMC7100521 | biostudies-literature
Project description:BackgroundNeonatal sepsis (NS), a life-threatening condition, is characterized by organ dysfunction and is the most common cause of neonatal death. However, the pathogenesis of NS is unclear and the clinical inflammatory markers currently used are not ideal for diagnosis of NS. Thus, exploring the link between immune responses in NS pathogenesis, elucidating the molecular mechanisms involved, and identifying potential therapeutic targets is of great significance in clinical practice. Herein, our study aimed to explore immune-related genes in NS and identify potential diagnostic biomarkers. Datasets for patients with NS and healthy controls were downloaded from the GEO database; GSE69686 and GSE25504 were used as the analysis and validation datasets, respectively. Differentially expressed genes (DEGs) were identified and Gene Set Enrichment Analysis (GSEA) was performed to determine their biological functions. Composition of immune cells was determined and immune-related genes (IRGs) between the two clusters were identified and their metabolic pathways were determined. Key genes with correlation coefficient > 0.5 and p < 0.05 were selected as screening biomarkers. Logistic regression models were constructed based on the selected biomarkers, and the diagnostic models were validated.ResultsFifty-two DEGs were identified, and GSEA indicated involvement in acute inflammatory response, bacterial detection, and regulation of macrophage activation. Most infiltrating immune cells, including activated CD8 + T cells, were significantly different in patients with NS compared to the healthy controls. Fifty-four IRGs were identified, and GSEA indicated involvement in immune response and macrophage activation and regulation of T cell activation. Diagnostic models of DEGs containing five genes (PROS1, TDRD9, RETN, LOC728401, and METTL7B) and IRG with one gene (NSUN7) constructed using LASSO algorithm were validated using the GPL6947 and GPL13667 subset datasets, respectively. The IRG model outperformed the DEG model. Additionally, statistical analysis suggested that risk scores may be related to gestational age and birth weight, regardless of sex.ConclusionsWe identified six IRGs as potential diagnostic biomarkers for NS and developed diagnostic models for NS. Our findings provide a new perspective for future research on NS pathogenesis.
| S-EPMC9972688 | biostudies-literature
Project description:BackgroundNeonatal sepsis is a serious condition. Recent clinical studies have indicated that microRNAs (miRNAs) are key players in the pathogenesis of sepsis, which could be used as biomarkers for this condition.Patients and methodsA total of 90 neonates with sepsis and 90 healthy neonates were enrolled in this study. qRT-PCR was performed to measure the expression levels of serum miR-34a-5p and miR-199a-3p.ResultsmiR-34a-5p and miR-199a-3p serum levels were significantly reduced in neonates with sepsis compared with those in healthy neonates (P = 0.006 and P = 0.001, respectively). Significant correlations of miR-34a-5p and miR-199a-3p with each of TLC, RDW, RBS, and C-reactive protein (CRP) as well as SNAPII were observed, indicating their associations with the severity of neonatal sepsis.ConclusionmiR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.
| S-EPMC8735601 | biostudies-literature
Project description:IntroductionNeonatal sepsis outreaches all causes of neonatal mortality worldwide and remains a major societal burden in low and middle income countries. In addition to limited resources, endemic morbidities, such as malaria and prematurity, predispose neonates and infants to invasive infection by altering neonatal immune response to pathogens. Nevertheless, thoughtful epidemiological, diagnostic and immunological evaluation of neonatal sepsis and the impact of gestational malaria have never been performed.Methods and analysisA prospective longitudinal multicentre follow-up of 580 infants from birth to 3 months of age in urban and suburban Benin will be performed. At delivery, and every other week, all children will be examined and clinically evaluated for occurrence of sepsis. At delivery, cord blood systematic analysis of selected plasma and transcriptomic biomarkers (procalcitonin, interleukin (IL)-6, IL-10, IP10, CD74 and CX3CR1) associated with sepsis pathophysiology will be evaluated in all live births as well as during the follow-up, and when sepsis will be suspected. In addition, whole blood response to selected innate stimuli and extensive peripheral blood mononuclear cells phenotypic characterisation will be performed. Reference intervals specific to sub-Saharan neonates will be determined from this cohort and biomarkers performances for neonatal sepsis diagnosis and prognosis tested.Ethics and disseminationEthical approval has been obtained from the Comité d'Ethique de la Recherche - Institut des Sciences Biomédicales Appliquées (CER-ISBA 85 - 5 April 2016, extended on 3 February 2017). Results will be disseminated through international presentations at scientific meetings and publications in peer-reviewed journals.Trial registration numberClinicalTrials.gov registration number: NCT03780712.
| S-EPMC7380952 | biostudies-literature
Project description:BackgroundThe objective of this study was to measure skin characteristics in premature (PT), late preterm (LPT), and full-term (FT) neonates compared with adults at two times (T1, T2).MethodsSkin samples of 61 neonates and 34 adults were analyzed for protein biomarkers, natural moisturizing factor (NMF), and biophysical parameters. Infant groups were: <34 weeks (PT), 34-<37 weeks (LPT), and ≥37 weeks (FT).ResultsForty proteins were differentially expressed in FT infant skin, 38 in LPT infant skin, and 12 in PT infant skin compared with adult skin at T1. At T2, 40 proteins were differentially expressed in FT infants, 38 in LPT infants, and 54 in PT infants compared with adults. All proteins were increased at both times, except TMG3, S100A7, and PEBP1, and decreased in PTs at T1. The proteins are involved in filaggrin processing, protease inhibition/enzyme regulation, and antimicrobial function. Eight proteins were decreased in PT skin compared with FT skin at T1. LPT and FT proteins were generally comparable at both times. Total NMF was lower in infants than adults at T1, but higher in infants at T2.ConclusionsNeonates respond to the physiological transitions at birth by upregulating processes that drive the production of lower pH of the skin and water-binding NMF components, prevent protease activity leading to desquamation, and increase the barrier antimicrobial properties.ImpactNeonates respond to the transitions at birth by upregulating processes that drive the production of lower pH of the skin and NMF, prevent protease activity leading to desquamation, and increase the antimicrobial properties of the barrier. The neonatal epidermal barrier exhibits a markedly different array of protein biomarkers both shortly after birth and 2-3 months later, which are differentially expressed versus adults. The major biomarker-functional classes included filaggrin processing, protease inhibitor/enzyme regulators, antimicrobials, keratins, lipids, and cathepsins. The findings will guide improvement of infant skin care practices, particularly for the most premature infants with the ultimate goals mitigating nosocomial infection.
| S-EPMC8119241 | biostudies-literature
Project description:BackgroundSepsis is the serious cause of fatality in the unit of medical-intensive care (ICU). Non-coding RNA transcripts are microRNA that control gene expression by repressing translation or degrading mRNA. There are several reports discussing the concept of using miRNAs as sepsis a biomarkers by profiling miRNA dysregulation in sepsis patients' blood samples.ObjectivesThe research was aimed at exploring the clinical utility of miRNA-16a and miRNA- 451 for diagnosis of neonatal sepsis.Subjectsand methods: This research was conducted on 50 full term neonates, 25 neonates with suspected or proven sepsis and 25 clinically healthy sex and age matched neonates with no evidence of sepsis. All newborns have been exposed to clinical review, history taking and laboratory investigations including total & differential count of blood cells, C-reactive protein, blood culture. Serum miRNA-16a and miRNA-451 levels have been assessed using Real Time polymerase chain reaction (Real Time PCR) technique.ResultsNeonates with sepsis had considerably higher levels of miRNA-16a and miRNA- 451 than the healthy neonates (p ≤ 0.001). Receiver operating curve (ROC) showed that serum miRNA-16a was superior to miRNA-451 for diagnosis of sepsis with neonatal origin; it had sensitivity and specificity of 88% and 98% versus 64% and 61% respectively. Cut off point for miRNA-16a to diagnose neonatal sepsis was above or equal 3.16. Also, cut off point for miRNA-451 was above or equal 1.26. miRNA-16 a and miRNA 451 expression was significantly correlated with respiratory rate, WBCs, and CRP.ConclusionBoth miRNA -16a and miRNA-451 are detected in higher levels in newborn with sepsis compared to controls. MiRNA- 16a could be considered as promising biomarkers for diagnosis of neonatal sepsis.
| S-EPMC7815658 | biostudies-literature
Project description:BackgroundNeonatal septicemia is a critical medical situation; current conventional laboratory methods still have many limitations and diagnostic obstacles. For this purpose, last decades have witnessed a challenge between the battery of sepsis biomarkers including many leukocyte surface antigens, not only for early diagnostic purposes but also for better follow-up and good management of sepsis patients.AimTo evaluate the diagnostic, prognostic, and monitoring performance of both neutrophil CD64 (nCD64) and presepsin as sepsis biomarkers compared to each other and to the conventional laboratory sepsis parameters aiming to decide which is the best fitting for routine daily use in neonatal intensive care units (NICUs).Methods235 neonates were enrolled from three Egyptian neonatal ICUs, during the period from November 2015 till March 2018; they were classified into two main groups: the control group (n = 102) and the sepsis group (n = 133). Laboratory sepsis evaluation included highly sensitive CRP (hs-CRP), CBC, in addition to nCD64 (flow cytometry technique), and presepsin measurement (CLEIA technique combined with Magtration® technology); the diagnosis was confirmed thereafter by positive blood culture results (BacT/Alert system). Sixty-two of the enrolled sepsis neonates were subjected to follow-up assessment; they were reclassified according to their clinical improvement at the second time assessment into (group 1: sepsis group without improvement) (n = 20) and (group 2: improved sepsis group) (n = 42).ResultsSignificant increase in nCD64 and presepsin values was found in sepsis groups compared to the controls. At cutoff 41.6%, nCD64% could discriminate the presence of septicemia with sensitivity 94.7%, specificity 93.6 %, and AUC 0.925, while presepsin at cutoff 686 pg/ml achieves sensitivity 82.7%, specificity 95.5%, and AUC 0.887, respectively. Significant increase in nCD64 (P < 0.001) and hs-CRP (P=0.018) values was observed in severe sepsis/septic shock patients compared to nonsevere sepsis patients. Delta change percentage (dC%) between initial and follow-up evaluations for both improved and nonimproved sepsis patients was dC Z value -5.904 for nCD64% followed by dC Z value -4.494 for presepsin.ConclusionnCD64 and presepsin are valuable early diagnostic and monitoring sepsis biomarkers; the highest sensitivity could be achieved by a univariant sepsis marker in this study was recorded by the nCD64% biomarker, while the highest specificity was documented by presepsin. Combined measurement of both achieves the highest diagnostic performance in sepsis neonates. Either of CD64 or presepsin combined with hs-CRP associated with better performance than any of them alone. nCD64 carries an additional promising role in reflecting sepsis prognosis.
| S-EPMC7654214 | biostudies-literature
Project description:IntroductionDiagnosing neonatal sepsis is heavily dependent on clinical phenotyping as culture-positive body fluid has poor sensitivity, and existing blood biomarkers have poor specificity.A combination of machine learning, statistical and deep pathway biology analyses led to the identification of a tripartite panel of biologically connected immune and metabolic markers that showed greater than 99% accuracy for detecting bacterial infection with 100% sensitivity. The cohort study described here is designed as a large-scale clinical validation of this previous work.Methods and analysisThis multicentre observational study will prospectively recruit a total of 1445 newborn infants (all gestations)-1084 with suspected early-or late-onset sepsis, and 361 controls-over 4 years. A small volume of whole blood will be collected from infants with suspected sepsis at the time of presentation. This sample will be used for integrated transcriptomic, lipidomic and targeted proteomics profiling. In addition, a subset of samples will be subjected to cellular phenotype and proteomic analyses. A second sample from the same patient will be collected at 24 hours, with an opportunistic sampling for stool culture. For control infants, only one set of blood and stool sample will be collected to coincide with clinical blood sampling. Along with detailed clinical information, blood and stool samples will be analysed and the information will be used to identify and validate the efficacy of immune-metabolic networks in the diagnosis of bacterial neonatal sepsis and to identify new host biomarkers for viral sepsis.Ethics and disseminationThe study has received research ethics committee approval from the Wales Research Ethics Committee 2 (reference 19/WA/0008) and operational approval from Health and Care Research Wales. Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites.Trial registration numberNCT03777670.
| S-EPMC8718461 | biostudies-literature