title: Circulating nucleosomes as a predictor of sepsis and organ dysfunction in critically ill patients.
abstract: OBJECTIVE
  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.affiliation: Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, QingChun Road 79, 310003 Hangzhou, China.
authors.forename: QiXing
authors.initials: Q
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: YuHong
authors.initials: Y
authors.lastname: Jin
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: TianZheng
authors.initials: T
authors.lastname: Lou
authors.forename: ZeLiang
authors.initials: Z
authors.lastname: Qiu
authors.forename: Yue
authors.initials: Y
authors.lastname: Jin
authors.forename: BaoLi
authors.initials: B
authors.lastname: Cheng
authors.forename: XiangMing
authors.initials: X
authors.lastname: Fang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000175:diagnosis*; D009707:Nucleosomes / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D018805:Sepsis / Q000097:blood / Q000175:diagnosis*; D018746:Systemic Inflammatory Response Syndrome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009707:Nucleosomes