Identification of immunologic and clinical characteristics that predict inflammatory response to C. Novyi-NT bacteriolytic immunotherapy.

BACKGROUND: Clostridium novyi-NT (CNV-NT), has shown promise as a bacterolytic therapy for solid tumors in mouse models and in dogs with naturally developing neoplasia. Factors that impact the immunologic response to therapy are largely unknown. The goal of this pilot study was to determine if plasma immune biomarkers, immune cell function, peripheral blood cytological composition and tumor characteristics including evaluation of a PET imaging surrogate of tumor tissue hypoxia could predict which dogs with naturally developing naïve neoplasia would develop an inflammatory response to CNV-NT. RESULTS: Dogs that developed an inflammatory response to CNV-NT had a higher heart rate, larger gross tumor volume, greater tumor [64Cu]ATSM SUVMax, increased constitutive leukocyte IL-10 production, more robust NK cell-like function and greater peripheral blood lymphocyte counts compared to dogs that did not develop an inflammatory response to CNV-NT. Of these, unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume appeared to be the best predictors of which dogs will develop an inflammatory response to CNV-NT. CONCLUSIONS: Development of inflammation in response to CNV-NT is best predicted by pretreatment unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume.

Regional citrate anticoagulation for PrismaFlex continuous renal replacement therapy.

BACKGROUND: Since Mehta et al. reported the first successful use of regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) in 1990, RCA is increasingly used for CRRT because it provides filter patency with minimal risk of bleeding. However, RCA has been associated with significant metabolic complications including hypocalcemia, hypernatremia, metabolic alkalosis, and citrate toxicity. OBJECTIVE: To describe our experience with a newly implemented RCA protocol with acid citrate dextrose formula A (ACD-A) and intravenous calcium gluconate, for use with PrismaFlex CRRT in critically ill patients with acute kidney injury. METHODS: A retrospective chart review was conducted from May 1, 2006, until May 1, 2007, in a 16-bed medical-surgical university-affiliated intensive care unit. Data collected included dialysis filter life, patient and circuit metabolic parameters, and units of packed red blood cells transfused. RESULTS: Forty-eight patients received dialysis with citrate (n = 178 filters). Circuit clotting occurred in 24% of all filters. Mean +/- SD filter life was 38.4 +/- 25.9 hours, and filter survival at 48 hours was 38.2%. Persistent metabolic alkalosis while on CRRT was identified in 6 of 45 (13.3%) patients. Mild hypocalcemia (ionized calcium <3.6 mg/dL) occurred in 11 (23%) patients, but no patient had an ionized calcium level less than 2.8 mg/dL. Six patients, 3 with acute leukemia, required transfusion of 2 or more units of packed red blood cells in 24 hours. CONCLUSIONS: We found that anticoagulation of PrismaFlex CRRT with ACD-A and intravenous calcium gluconate provided reasonable filter patency, but with minor metabolic complications. Close monitoring of electrolyte and acid-base balance is required to minimize metabolic derangements.