Clinical Assays in Sepsis: Prognosis, Diagnosis, Outcomes, and the Genetic Basis of Sepsis

Sepsis is the most widespread medical disorder of the intensive care unit (ICU) and the most common cause of death in hospitalized patients. Several endothelium-related molecules have been investigated as potential biomarkers for early diagnosis and/or prognosis of sepsis, providing different results depending on study designs. Therefore, it seems that we are still far from the right combination of sepsis markers to be used in clinical practice. It is more probable that a panel of diverse biomarkers will be more efficient in clinical practice. More recently, the potential use of genetic biomarkers for prognostic purposes started emerging for sepsis, in the form of genome-wide association studies. The successful use of modern molecular diagnostics could enable rapid identification of particularly susceptible or less susceptible individuals, leading to tailored therapeutic treatments

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

INTRODUCTION: Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. METHODS: Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFα) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFα, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. RESULTS: Mortality rates of patients with apoptosis ≤50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis ≤50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis ≤50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFα were higher in patients with monocyte apoptosis ≤50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. CONCLUSION: Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis