Relative Adrenal Insufficiency Is a Risk Factor for Pediatric Sepsis: A Proof-of-Concept Study.
J Infect Dis
; 229(4): 1166-1177, 2024 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-37633660
ABSTRACT
Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% of patients with pediatric septic develop relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day-old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited a substantially higher mortality rate in cecal ligation and puncture and cecal slurry-induced sepsis. These mice featured persistent inflammatory responses and were effectively rescued by GC therapy. RNA sequencing analysis revealed persistent inflammatory responses in RAI mice, caused by transcriptional dysregulation of AP-1 and NF-κB, and cytokine-induced secondary inflammatory response. Our findings support a precision medicine approach to guide GC therapy for pediatric patients based on the status of RAI.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Adrenal
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Sepse
Tipo de estudo:
Etiology_studies
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Guideline
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Child
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Humans
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2024
Tipo de documento:
Article