Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun;31(3):322-327.
doi: 10.1097/MOP.0000000000000753.

Precision medicine in pediatric sepsis

Affiliations
Review

Precision medicine in pediatric sepsis

Mihir R Atreya et al. Curr Opin Pediatr. 2019 Jun.

Abstract

Purpose of review: Pediatric sepsis is a heterogeneous state associated with significant morbidity and mortality, but treatment strategies are limited. Clinical trials of immunomodulators in sepsis have shown no benefit, despite having a strong biological rationale. There is considerable interest in application of a precision medicine approach to pediatric sepsis to identify patients who are more likely to benefit from targeted therapeutic interventions.

Recent findings: Precision medicine requires a clear understanding of the molecular basis of disease. 'Omics data' and bioinformatics tools have enabled identification of endotypes of pediatric septic shock, with corresponding biological pathways. Further, using a multibiomarker-based approach, patients at highest risk of poor outcomes can be identified at disease onset. Enrichment strategies, both predictive and prognostic, may be used to optimize patient selection in clinical trials and identify a subpopulation in whom therapy of interest may be trialed. A bedside-to-bench-to-bedside model may offer clinicians pragmatic tools to aid in decision-making.

Summary: Precision medicine approaches may be used to subclassify, risk-stratify, and select pediatric patients with sepsis who may benefit from new therapies. Application of precision medicine will require robust basic and translational research, rigorous clinical trials, and infrastructure to collect and analyze big data.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: Dr. Wong and Cincinnati Children’s Hospital Medical Center hold United States patents for the PERSEVERE biomarkers and the endotyping strategy described in this manuscript.

References

    1. Weiss SL, Fitzgerald JC, Pappachan J, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015;191(10):1147–1157. doi:10.1164/rccm.201412-2323OC - DOI - PMC - PubMed
    1. Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis*. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2013;14(7):686–693. doi:10.1097/PCC.0b013e3182917fad - DOI - PubMed
    1. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2005;6(1):2–8. doi:10.1097/01.PCC.0000149131.72248.E6 - DOI - PubMed
    1. Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, et al. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 2013;93(3):1247–1288. doi:10.1152/physrev.00037.2012 - DOI - PMC - PubMed
    1. Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med. 2014;20(4):195–203. doi:10.1016/j.molmed.2014.01.007 - DOI - PubMed

Publication types