Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis

Wynn, James L.; Guthrie, Scott O.; Wong, Hector R.; Lahni, Patrick; Ungaro, Ricardo; López, María Cecilia; Baker, Henry V.; Moldawer, Lyle L.

doi:10.2119/molmed.2015.00064

Cited by 58 publications

(80 citation statements)

References 45 publications

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“…In the supervised analysis, significant genes were identified using an F-test at p<0.001. Leave-one-out cross-validation and Monte Carlo simulations and permutation analysis were used to determine whether the misclassification rate for each subject (term, preterm, or adult) was significantly better than predicted by chance, using BRB ArrayTools™ Version:4.5.1-Stable Release as described previously [11–13]. …”

Section: Methodsmentioning

confidence: 99%

Neutrophil chemotaxis and transcriptomics in term and preterm neonates

Raymond

Mathias

Murphy

et al. 2017

Translational Research

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Neutrophils play a crucial role in combating life-threatening bacterial infections in neonates. Previous studies investigating neonatal cell function have been limited because of restricted volume sampling. Here, using novel microfluidics approaches, we provide the first description of neutrophil chemotaxis and transcriptomics from whole blood of human term and preterm neonates, as well as young adults. Ex vivo percent cell migration, neutrophil velocity, and directionality to fMLP were measured from whole blood using time-lapse imaging of microfluidic chemotaxis. Genome-wide expression was also evaluated in CD66b+ cells using microfluidic capture devices. Neutrophils from preterm neonates migrated in fewer numbers compared to term neonates (preterm 12.3%, term 30.5%, p=0.008) and at a reduced velocity compared to young adults (preterm 10.1 μm/min, adult 12.7 μm/min, p=0.003). Despite fewer neutrophils migrating at slower velocities, neutrophil directionality from preterm neonates was comparable to adults and term neonates. 3,607 genes were differentially expressed among the three groups (p<0.001). Differences in gene expression between neutrophils from preterm and term neonates were consistent with reduced pathogen recognition and antimicrobial activity, but not neutrophil migration, by preterm neonates. In summary, preterm neonates have significant disturbances in neutrophil chemotaxis compared to term neonates and adults, and these differences in phenotype appear at the transcriptional level to target inflammatory pathways in general, rather than in neutrophil migration and chemotaxis.

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Section: Methodsmentioning

confidence: 99%

Neutrophil chemotaxis and transcriptomics in term and preterm neonates

Raymond

Mathias

Murphy

et al. 2017

Translational Research

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“…7 We also did a subgroup analysis of HRC scores among the patients with BSI (with exclusion of all CoNS) that had serum C reactive protein (≥45 mg/L) during the episode. 13 …”

Section: Methodsmentioning

confidence: 99%

Heart rate characteristic index monitoring for bloodstream infection in an NICU: a 3-year experience

Coggins

Weitkamp

Grunwald

et al. 2015

Arch Dis Child Fetal Neonatal Ed

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Background Blood stream infection (BSI) among Neonatal Intensive Care Unit (NICU) infants is a frequent problem associated with poor outcomes. Monitoring for abnormal heart rate characteristics (HRC) may decrease infant mortality by alerting clinicians to sepsis before it becomes clinically apparent. Methods HRC scores were acquired using the HRC (HeRO) monitor system from Medical Predictive Science Corporation and entered into the electronic medical record by bedside staff. We retrospectively analyzed HRC scores recorded twice daily in the medical record during a 30-month period (January 1, 2010 through June 30, 2012) for infants in the NICU at the Monroe Carell Jr. Children’s Hospital at Vanderbilt. We identified infants that met CDC criteria for late-onset BSI (>3 days of life) during the study period. Results During the study period, we recorded 127,673 HRC scores from 2384 infants. We identified 46 infants with BSI. Although 8% (9701/127,673) of the HRC scores were ≥2 and 1% (1387/127,673) were ≥5, BSI (at any time) was observed in just 5% of patients with HRC scores ≥2, and 9% of patients with HRC scores ≥5. Of infants with BSI, 5/46 (11%) had at least one HRC score ≥5 and 17/46 (37%) had at least one score ≥2 recorded in the 48 hour period prior to the evaluation that resulted in the first positive blood culture of the episode. Conclusion In our single center retrospective study, elevated HRC scores had limited ability to detect BSI. BSI was infrequent at any time during hospitalization in infants with significantly elevated HRC scores.

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“…25 This points to the utility of unsupervised transcriptomic clustering to discover important clinical differences in sepsis.…”

Section: Unsupervised Learning Of Sepsis Subtypesmentioning

confidence: 99%