| Objective To investigate whether circulating cell-free(cf)-DNA levels are a useful biomarker for survival in patients with shock in the emergency intensive care unit(EICU).Methods This prospective observational study enrolled 173 patients admitted to the EICU diagnosed with shock of the First Affiliated Hospital of Anhui Medical University between June 2012 and April 2015.On admission to the EICU and after 24 h and 48 h,5ml of whole blood was obtained from each patient.Plasma cf-DNA was measured using a SYBR Green dye-based quantitative real-time PCR assay for the human b-globin gene,a housekeeping gene.Meanwhile,APACHE II score at admission and lactate levels among 24 h after admission of EICU shock patients were recorded.Ageand sex-matched controls were recruited from the Physical Examination Centre,First Affiliated Hospital of Anhui Medical University between June 2012 and August 2012.Total patients were divided into two groups according clinical outcomes: survivors and non-survivors.Blood cf-DNA levels were analysed on admission,and after 24 and 48 h and APACHE II score at admission and lactate levels among 24 h after admission of EICU shock patients also were analysed,which to explored the connection between those variables and patient outcomes.Results Circulating cf-DNA levels were higher at admission and after 24 h in EICU patientswith shock who died than in those who recovered,8.02*10^5pg/ml(2.71*10^5-1.98*10^6)vs1.20*10^5pg/ml(4.59*10^4-3.12*10^5)(P<0.001)?5.23*10^5 pg/ml(2.94*10^5-2.05*10^6)vs9.06*10^4 pg/ml(3.38*10^4-3.19*10^5)(P<0.001).Change in cf-DNA levels over the first 48 h in critical care was statistically significantly higher in patients who died(+37.93%(-1.07-+137.88%))than in patients survived(-26.06%(-2.56%--50.96%))(P<0.001).In addition,APACHE II score at admission and lactate levels among 24 h after admission of non-survivors also were higher than survivors,24.9±7.2vs19.3±7.1(P<0.001),2.38mmol/l(1.56mmol/l-5.62mmol/l)vs1.28mmol/l(0.93mmol/l-2.65mmol/l)(P<0.001).Using receiver operating characteristic curve analysis,the area under the curve(AUC)of circulating cf-DNA levels at admission was 0.808(0.719-0.896),the optimal cut-off value was 635119.5 pg/ml(sensitivity 62.2%,specificity 89.7%).The AUC of circulating cf-DNA levels after 24 h was 0.830(0.753-0.907),the optimal cut-off value was 325779.5 pg/ml(sensitivity 73.3%,specificity 77.6%).In multiple logistic regression analysis,the circulating cf-DNA change over 48 h was significant as predictive of 28-day mortality,the AUC was 0.825(0.741-0.909),the optimal cut-off value was +16.12%(sensitivity 62.2%,specificity 89.7%).Conclusions Circulating cf-DNA concentrations in EICU patients with shock were significantly higher than in healthy controls.Circulating cf-DNA concentrations at EICU admission and after 24 h were significantly higher in patients with shock who died than in those who survived at least 28 days.Lactate levels at 24 h and APACHE II scores at EICU admission had lower predictive values for 28-day mortality than cf-DNA concentrations.The most accurate predictor of fatal outcome for a patient in the EICU with shock was cf-DNA change over the first 48 h of critical care.The cut-off value for cf-DNA change over 48 h found in the present study may help physicians in deciding which patients with shock should continue with escalatingtreatment and which can be discharged from the EICU. |
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