Assessment of early oxidative stress following the use of radiotheranostics agents 177Lu-PSMA for prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors; Radioprotective effect of vitamin C

Background: We aimed first to evaluate the early oxidative stress following radionuclide therapy (RNT) with 177Lu-PSMA and 177Lu-DOTATATE and second to evaluate the protective effect of vitamin C on oxidative stress. Materials and methods: Prostate cancer and neuroendocrine tumor (NET) patients referred to therapy with 177Lu-PSMA and 177Lu-DOTATATE, respectively, were enrolled in this study. The patients divided into the control group underwent routine RNT without any intervention and the intervention group was asked to take effervescent tablets (500 mg) of vitamin C for two days prior to the RNT (three tablets per day). To measure oxidative stress, blood samples were taken immediately before treatment and 48 h after treatment, and the serums were separated and frozen. To evaluate oxidative stress, the serum levels of malondialdehyde (MDA) and glutathione (GSH) and the activity of glutathione reductase were measured before and two days after treatment. Results: In total, 61 RNT cycles were evaluated in 34 patients with age of 65 ± 2.83 (median ± SE) years (range of 27-99); this total included 20 (59%) prostate cancer patients [35 cycles (57.4%)] and 14 patients (41%) with NET [26 cycles (42.6%)]. Of the 61 evaluated cycles, 27 cycles were given in the control group and 34 cycles were given in the intervention group. The serum level of MDA was significantly increased after treatment compared to before treatment (P = 0.02) in the control group, while no significant change in the serum level of MDA was observed in the intervention group (P = 0.52). The serum level of GSH was insignificantly decreased after treatment compared to before treatment in the control group and slightly increased after treatment in the intervention group (P > 0.05). The serum level of glutathione reductase was insignificantly increased in all groups of patients after treatment (P > 0.05). Conclusion: According to the results of this study, RNT with Lu-PSMA and Lu-DOTATATE may induce oxidative stress via the generation of free radicals and reactive oxygen species. Consumption of vitamin C prior to RNT may ameliorate this oxidative stress. These preliminary results have positive implications for clinical practice. Verification of these noteworthy results is needed and can be conducted with larger randomized controlled trials with longer time points

The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial

INTRODUCTION Postoperative delirium is one of the most common complications of major surgery, affecting 10-70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial. METHODS The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study is an international, multicentre, randomised controlled trial. 600 cardiac and major non-cardiac surgery patients will be randomised to receive ketamine (0.5 or 1 mg/kg) or placebo following anaesthetic induction and prior to surgical incision. For the primary outcome, blinded observers will assess delirium on the day of surgery (postoperative day 0) and twice daily from postoperative days 1-3 using the Confusion Assessment Method or the Confusion Assessment Method for the ICU. For the secondary outcomes, blinded observers will estimate pain using the Behavioral Pain Scale or the Behavioral Pain Scale for Non-Intubated Patients and patient self-report. ETHICS AND DISSEMINATION The PODCAST trial has been approved by the ethics boards of five participating institutions; approval is ongoing at other sites. Recruitment began in February 2014 and will continue until the end of 2016. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement and popular media. REGISTRATION DETAILS The study is registered at clinicaltrials.gov, NCT01690988 (last updated March 2014). The PODCAST trial is being conducted under the auspices of the Neurological Outcomes Network for Surgery (NEURONS). TRIAL REGISTRATION NUMBER NCT01690988 (last updated December 2013)