The HC alcohol intake was <20 g/day and volunteers had not

drunk alcohol or exercised excessively in the 24 hours prior to blood being drawn. SC patients were recruited from the general ICU and had severe sepsis with MODS. Severe sepsis was defined by the presence of an SIRS score ≥2,16 with radiological and/or laboratory evidence of infection and one or more extrahepatic organ failure(s). Patients presenting with ALF/SALF were given empirical intravenous antibiotic and antifungal cover as standard of care. This DAPT concentration consisted of tazocin 4.5 g every 8 hours (substituted for meropenem 1 g every 8 hours if penicillin allergic) and fluconazole 400 mg once daily. Patients were excluded from the ALF/SALF cohorts if on presentation they had evidence of bacterial, fungal, or viral infection on clinical examination, radiological or laboratory investigation, malignancy, and any coexisting history of immunodeficiency including human immunodeficiency virus (HIV) and glycogen storage disease. Patients with preexisting liver disease, a history of alcohol intake >20g/day, or who were on immunosuppressive therapies such PLX3397 solubility dmso as steroids or azathioprine were also excluded. The study was performed in accordance with the Declaration of Helsinki and ethical

permission was granted from the North East London Research Ethics Committee (Ref. No. 08/H0702/52). Following obtaining fully informed consent/assent, clinical, biochemical, and physiological data were collected. Data included tobacco and alcohol use, arterial ammonia (μmol/L), serum sodium levels (mmol/L), arterial blood gas analysis including lactate (mmol/L), differential leukocyte count see more (×109), complement, and immunoglobulin and lipoprotein levels. SIRS score16 was also calculated on admission and on subsequent neutrophil sampling days. A number of organ failure scores were also quantified including the model of endstage liver disease score (MELD), sequential organ failure assessment score (SOFA),17 and the acute physiology and chronic health evaluation

(APACHE) II score.18 Length of ICU stay, survival, and number of days requiring vasopressors, ventilation, or hemofiltration were also recorded. Antibiotic use and details of potentially immunomodulatory therapies such as corticosteroids, hypothermia, hemofiltration, and plasmapheresis were recorded. The occurrence of bacterial and fungal infection was recorded along with other relevant patient outcomes including the development of organ failure and 90-day survival. Venous blood was collected aseptically from patients/volunteers into heparinized pyrogen-free tubes and was immediately precooled to 0-4°C for 10 minutes. Neutrophil phenotype and function test analyses were performed within 1 hour of blood being drawn.