Objectives: to investigate the prognostic value of circulating levels of cell-free DNA in patients withsepsis in the intensive care setting regarding the clinical course and final outcome. Moreover, to compare thisprognostic value of circulating cell-free DNA levels with other commonly used biochemical markers forprognosis of sepsis (CRP and Procalcitonin) and with the APACHE II and SOFA scoring systems. We tried todescribe the gastric mucosal morphologic abnormalities occurring in the septic settings, then we attempted tocorrelate these findings with clinical course, prognosis and mortality of septic patients.Design: A prospective, randomized, single center study. Setting: Critical Care Department(medical/surgical ICU), Cairo University Hospitals.Patients: 30 critically ill patients admitted to the Critical Care Department, Cairo University Hospitalswith a diagnosis of sepsis. Intervention: All included septic patients were subjected to the upper GIT endoscope,which was performed at ICU admission and once again during ICU stay (approximately one week later) to obtaina gastric mucosal biopsy for histopathological microscopic examination. Measurements: Cell-free plasma DNAconcentrations (measured by real-time polymerase chain reaction assay for the ß- globin gene), CRP levels andProcalcitonin concentrations were all measured on admission to the ICU. APACHE II score was calculated once(in the first 24h of ICU admission) and SOFA score was calculated at baseline and subsequently thereaftereveryday until ICU discharge or death or up to a total of 28 days. Clinical outcome (duration of stay in the ICU,need for mechanical ventilation, need for inotropic/vasopressor support, need for haemodialysis, and finaloutcome of survival/mortality rates) were recorded for all patients.Results: The median plasma DNA concentration in critically ill septic patients was 186.5 ng/ml and thiswas significantly (approximately 7-fold) higher than the median DNA concentration in healthy subjects 26ng/ml, (P < 0.001). The patients who required mechanical ventilation had significantly higher median DNAconcentration compared to those who did not require it (208.9 ng/ml versus 65.5 ng/ml; P = 0.001). The patientswho were on inotropic/vasopressor support had significantly higher DNA concentrations compared to nonsupportedpatients (235 ng/ml versus 114.6 ng/ml; P < 0.001). The median plasma DNA level was significantlyhigher in patients who required haemodialysis (244.2 ng/ml versus 169.1 ng/ml; P = 0.011). DNA concentrationdemonstrated a significant correlation with C-reactine protein (CRP) concentration (r = 0.656, P <0.001),procalcitonin concentration (PCT) ( r = 0.835, P <0.001), and Sepsis-related Organ Failure Assessment (SOFA)score ( r = 0.860, P <0.001), but not with Acute Physiology And Chronic Health Evaluation (APACHE II) score( r = 0.273, P =0.145), DNA concentration demonstrated insignificant negative correlation with length of ICUstay ( r = -0.044, P =0.818). The median plasma DNA concentration in nonsurvivors was 240 ng/ml, and thiswas significantly (approximately 2-fold) higher than that in survivors 114.6 ng/ml, (P < 0.001). ROC analysis ofthe data indicated a sensitivity of 100% and a specificity of 100% when DNA concentration of 186.5 ng/ml wastaken as a predictor of ICU mortality. The 1st gastric mucosal biopsies showed 5 different gastric mucosalchanges and the2nd biopsies revealed 9 (5 were also previously detected in the 1st biopsies and 4 newly describedin the 2nd biopsies) different gastric mucosal morphologic abnormalities (with varying degrees of severity fromsuperficial gastritis to superficial erosions). Patients with septic shock at their ICU admission had a significantincrease in superficial erosions and a significant decrease in superficial gastritis in their 2nd gastric mucosalbiopsies when compared to non-septic shock patients (P = 0.033 , P = 0.032 respectively ).There was also a trendtoward increased frequency of superficial erosions in nonsurvivors versus survivors in their 2nd biopsies (P =0.065).Conclusion: Circulating DNA concentrations were elevated early in patients who were admitted to theICU with sepsis when compared to healthy controls, cell-free plasma DNA concentrations were significantlyhigher in patients who needed organ supportive measures (mechanical ventilation, inotropic/vasopressor supportand haemodialysis) during their ICU stay, cell free plasma DNA levels were significantly higher in ICUnonsurvivors than in survivors. Circulating DNA concentrations demonstrated a significant correlation with CRP,PCT concentrations and SOFA score, but not with APACHE II score or length of ICU stay. These findingsindicate that plasma cell-free DNA might be used as a potential useful marker for evaluation of septic patientswhen admitted to ICU and for prediction of their adverse outcomes. Patients with septic shock at ICU admissiondemonstrated a significant increase in superficial erosions and a significant decrease in superficial gastritis intheir 2nd gastric mucosal biopsies when compared to non-septic shock patients. In addition, there was a trendtoward icreased superficial erosions in non-survivors in their 2nd biopsies (P = 0.065) when compared tosurvivors. These findings indicate that more severe gastric mucosal lesions were detected in septic shock patientsand nonsurvivors.