Circulating nucleosomes as a predictor of sepsis and organ dysfunction in critically ill patients.

Abstract

OBJECTIVES:

Sepsis is a leading cause of death in critically ill patients, and apoptosis plays a major role in the pathophysiology of sepsis. Elevated levels of circulating nucleosomes released by apoptotic cells have been detected in patients with severe sepsis and septic shock. The aim of this study was to evaluate the diagnostic/prognostic value of circulating nucleosomes in sepsis.

METHODS:

Seventy-four newly admitted patients with an estimated length of stay in the intensive care unit of more than 48 h, were prospectively enrolled as cohort 1. The second independent cohort (cohort 2) consisted of 91 post-surgery patients. Patients receiving chemotherapy, those with AIDS, those on steroid treatment, and those undergoing transplants were excluded. Levels of circulating nucleosomes within 24h of admission in both cohorts, and for cohort 1 also on days 3, 5, and 7 and a last time-point of ICU discharge or at imminent death, were measured and analyzed for their capacity to predict sepsis. The severity of the inflammatory response and organ dysfunction were assessed by cytokine levels and sepsis scores.

RESULTS:

Nucleosome levels on admission in septic patients were significantly higher than those in non-septic controls in both of the cohorts. The area under the receiver operating characteristic curve for admission nucleosome levels to differentiate septic patients from non-septic patients was 0.70 (95% confidence interval (CI) 0.51-0.88) in cohort 1, 0.66 (95% CI 0.55-0.79) in cohort 2, and 0.67 (95% CI 0.55-0.79) in all of the subjects. After multiple logistic regression analysis, circulating nucleosomes remained as an independent predictor of sepsis. Furthermore, the levels of circulating nucleosomes on admission were significantly correlated with the inflammatory response and organ dysfunction in sepsis. Meanwhile, a trend was observed for admission levels of circulating nucleosomes in non-survivors to be higher than those in survivors.

CONCLUSIONS:

The level of circulating nucleosomes in the serum has a predictive value for sepsis and organ dysfunction and may serve as a candidate biomarker for the diagnosis/prognosis of sepsis. Further studies are warranted to confirm the present findings.

• Authors: QiXing Chen, Ling Ye, YuHong Jin, Ning Zhang, TianZheng Lou, ZeLiang Qiu, Yue Jin, BaoLi Cheng, XiangMing Fang
• Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (Int J Infect Dis) Vol. 16 Issue 7 Pg. e558-64 (Jul 2012) ISSN: 1878-3511 [Electronic] Canada
• PMID: 22609014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers
• Nucleosomes

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Critical Illness
• Female
• Humans
• Intensive Care Units
• Male
• Middle Aged
• Multiple Organ Failure (blood, diagnosis)
• Nucleosomes (metabolism)
• Predictive Value of Tests
• Prognosis
• Sepsis (blood, diagnosis)
• Systemic Inflammatory Response Syndrome
• Young Adult