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Circulating Histones and Severity of Illness in Children with Sepsis: A Prospective Observational Study
Vishal Sidana1, Javed Ismail2, Karthi Nallasamy3
1Pediatric Intensive Care Unit, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Insights
Circulating histone H3 levels were not elevated in children with severe sepsis compared to healthy controls. Histone H3 did not correlate with illness severity or organ failure in pediatric sepsis patients.
Area of Science:
- Pediatric critical care medicine
- Infectious diseases
- Biomarker research
Background:
- Severe sepsis is a life-threatening condition in children.
- Identifying reliable biomarkers for sepsis severity is crucial for timely intervention.
- Histone H3 is a potential biomarker implicated in inflammatory responses.
Purpose of the Study:
- To measure circulating histone H3 levels in children with severe sepsis.
- To investigate the relationship between histone H3 levels and disease severity, organ dysfunction, and outcomes in pediatric sepsis.
Main Methods:
- Prospective study of children aged 3 months to 12 years with severe sepsis admitted to the pediatric intensive care unit (PICU).
- Inclusion of healthy children as controls.
- Measurement of histone H3 levels on day 1 and day 3 of admission.
Main Results:
- No statistically significant difference in histone H3 levels between severe sepsis patients and healthy controls.
- Histone H3 levels did not change significantly between day 1 and day 3 in sepsis patients.
- A trend towards higher histone H3 levels was observed in children with thrombocytopenia (p=0.06).
- Histone H3 levels were not elevated in patients with cardiovascular dysfunction, renal replacement therapy, or unfavorable outcomes.
Conclusions:
- Circulating histone H3 is not elevated in children with severe sepsis compared to healthy controls.
- Histone H3 levels do not appear to correlate with illness severity, organ dysfunction, or clinical outcomes in pediatric sepsis.
- Further research is warranted to explore the potential role of histone H3 in pediatric thrombocytopenia associated with sepsis.
Objectives:
To measure circulating histone H3 levels in children with severe sepsis and explore its relationship with severity of illness and organ failures.
Methods:
Children aged 3 mo to 12 y with severe sepsis admitted to pediatric intensive care unit (PICU) were prospectively studied. Healthy controls were enrolled from the outpatient department for comparison. Levels of H3 histones were measured on day 1 and day 3.
Results:
Thirty-seven patients and 14 controls with median (IQR) age 5 (0.67, 8) and 5 (3, 7) y, respectively were enrolled. Common diagnoses included severe pneumonia (n = 9), staphylococcal sepsis (n = 6), and seasonal tropical infections (n = 4). Two-third (n = 26, 70%) had septic shock. One third (35%) had an unfavorable outcome; 11 died and 2 discontinued care. Median (IQR) H3 levels were not statistically different among patients with sepsis and controls [0.84 (0.62, 1.13) vs. 0.72 (0.52, 0.87) ng/mL; p = 0.10]. There was no significant change in H3 between day 1 and day 3 [0.84 (0.62, 1.13) vs 0.74 (0.5, 0.98) ng/mL; p = 0.22]. Children with thrombocytopenia (n = 27) showed a trend towards higher H3 compared to those without thrombocytopenia (n = 10) [0.9 vs. 0.67 ng/mL; p = 0.06]. However, H3 levels were not elevated in patients with cardiovascular dysfunction, those needing renal-replacement therapy, or unfavorable outcomes.
Conclusion:
The present data provides early evidence that in children hospitalized with severe sepsis, histone H3 is not elevated as compared to healthy controls. H3 levels during initial days of sepsis requiring PICU admission were not different with regards to severity of illness, organ dysfunction, and clinical outcome. There was a trend towards elevated H3 in children with thrombocytopenia, which needs further evaluation.
