Introduction of antineoplastic drug NSC631570 in an inpatient and outpatient setting:Comparative evaluation of biological effects

The aim of this study is to evaluate the effect of moderate physical exercise and treatment time on the organism’s response to NSC631570. The sensitivity of circulating phagocytes to the drug at different times of day was estimated in in vitro experiments. NSC631570 was administered intravenously to healthy volunteers (eleven men, 23 ± 2 years) in a single therapeutic dose in an inpatient and an outpatient setting. Blood samples were obtained before the drug administration, 30 min after the drug injection and every fourth hour throughout the 24 hour period. Biochemical parameters were determined using the hematological analyzer. Flow cytometry was used to evaluate phagocyte metabolism. Treatment of circulating phagocytes with NSC631570 in vitro resulted in an increase in ROS production along with a decrease in their phagocytic activity, most expressed in the morning time. Drug injection to sedentary persons resulted in pro-inflammatory metabolic polarization of circulating phagocytes. Introduction of NSC631570 to active persons was accompanied by a significant increase in phagocyte endocytosis along with a decrease in the daily mean of ROS generation. Significant oscillation (but in the normal ranges) of urea, creatinine, alanine aminotransferase and aspartate aminotransferase after NSC631570 introduction in the outpatient setting was shown during the day. Physical activity interferes with immunomodulatory action of NSC631570 and abrogates pro-inflammatory shift of circulating phagocytes. Biochemical parameters of blood from patients treated with NSC631570 in the outpatient setting must be interpreted cautiously considering the effect of physical activity on some metabolic biomarkers.

Routine laboratory parameters in patients with necrotizing pancreatitis by the time of operative pancreatic debridement:Food for thought

BACKGROUND Timing of invasive intervention such as operative pancreatic debridement(OPD)in patients with acute necrotizing pancreatitis(ANP)is linked to the degree of encapsulation in necrotic collections and controlled inflammation.Additional markers of these processes might assist decision-making on the timing of surgical intervention.In our opinion,it is logical to search for such markers among routine laboratory parameters traditionally used in ANP patients,considering simplicity and cost-efficacy of routine laboratory methodologies.AIM To evaluate laboratory variables in ANP patients in the preoperative period for the purpose of their use in the timing of surgery.METHODS A retrospective analysis of routine laboratory parameters in 53 ANP patients undergoing OPD between 2017 and 2020 was performed.Dynamic changes of routine hematological and biochemical indices were examined in the preoperative period.Patients were divided into survivors and non-survivors.Survivors were divided into subgroups with short and long post-surgery length of stay(LOS)in hospital.Correlation analysis was used to evaluate association of laboratory variables with LOS.Logistic regression was used to assess risk factors for patient mortality.RESULTS Seven patients(15%)with severe acute pancreatitis(SAP)and 46 patients(85%)with moderately SAP(MSAP)were included in the study.Median age of participants was 43.2 years;33(62.3%)were male.Pancreatitis etiology included biliary(15%),alcohol(80%),and idiopathic/other(5%).Median time from diagnosis to OPD was≥4 wk.Median postoperative LOS was at the average of 53 d.Mortality was 19%.Progressive increase of platelet count in preoperative period was associated with shortened LOS.Increased aspartate aminotransferase and direct bilirubin(DB)levels the day before the OPD along with weak progressive decrease of DB in preoperative period were reliable predictors for ANP patient mortality.CONCLUSION Multifactorial analysis of dynamic changes of routine laboratory variables can be useful for a person-tailored timing of surgical intervention in ANP patients.