Interpreting Testosterone and Concomitant Prostate Specific Antigen Values during Androgen Deprivation Therapy for Recurrent Prostate Cancer.

PURPOSE: Measurement of testosterone levels during androgen deprivation therapy (ADT) is broadly recommended, but how therapy should be altered in response to testosterone values during ADT remains controversial. Our objective was therefore to evaluate the relation between testosterone and concomitant prostate specific antigen (PSA) levels during ADT on clinical outcomes. MATERIALS AND METHODS: Patients from the continuous androgen deprivation arm of the PR.7 trial of intermittent ADT for biochemically recurrent prostate cancer following radiotherapy were included. Statistical analyses evaluated the prognostic importance of testosterone levels during ADT relative to concomitant PSA levels. We similarly evaluated whether the number of testosterone breakthroughs >1.7 nmol/l predicted the time to castrate-resistant prostate cancer (CRPC), cancer specific survival (CSS) or overall survival (OS) with Kaplan-Meier and Cox regression analyses. RESULTS: Overall, the prognostic importance of testosterone on outcomes was eclipsed by the prognostic value of concomitant PSA values. The occurrence of testosterone values >0.7 nmol/l in the first year of therapy was associated with subsequent rises >1.7 nmol/l, but the number of testosterone breakthroughs per patient had no relationship to the risk of CRPC, CSS or OS. A time-dependent adjusted analysis indicated as expected that PSA values were prognostic, but there was no association of relative cumulative testosterone exposure with outcomes. CONCLUSIONS: In this large-scale trial with long followup, breakthrough testosterone was unrelated to time to CRPC, CSS or OS. Castrate testosterone values during ADT for recurrent prostate cancer provides prognostic information that must be considered alongside the time since ADT initiation and concomitant PSA values.

A new tool for assessing short debriefings after immersive simulation: validity of the SHORT scale.

BACKGROUND: Simulation is being increasingly used worldwide in healthcare education. However, it is costly both in terms of finances and human resources. As a consequence, several institutions have designed programs offering several short immersive simulation sessions, each followed by short debriefings. Although debriefing is recommended, no tool exists to assess appropriateness of short debriefings after such simulation sessions. We have developed the Simulation in Healthcare retrOaction Rating Tool (SHORT) to assess short debriefings, and provide some validity evidence for its use. METHODS: We designed this scale based on our experience and previously published instruments, and tested it by assessing short debriefings of simulation sessions offered to emergency medicine residents at Laval University (Canada) from 2015 to 2016. Analysis of its reliability and validity was done using Standards for educational and psychological testing. Generalizability theory was used for testing internal structure evidence for validity. RESULTS: Two raters independently assessed 22 filmed short debriefings. Mean debriefing length was 10:35 (min 7:21; max 14:32). Calculated generalizability (reliability) coefficients are φ = 0.80 and φ-λ3 = 0.82. The generalizability coefficient for a single rater assessing three debriefings is φ = 0.84. CONCLUSIONS: The G study shows a high generalizability coefficient (φ ≥ 0.80), which demonstrates a high reliability. The response process evidence for validity provides evidence that no errors were associated with using the instrument. Further studies should be done to demonstrate validity of the English version of the instrument and to validate its use by novice raters trained in the use of the SHORT.

Telegraphic noise in transport through colloidal quantum dots.

We report measurements of electrical transport through single CdSe/CdS core/shell colloidal quantum dots (cQDs) connected to source and drain contacts. We observe telegraphic switching noise showing few plateaus at room temperature. We model and interpret these results as charge trapping of individual trap states, and therefore we resolve individual charge defects in these high-quality low-strain cQDs. The small number of observed defects quantitatively validates the passivation method based on thick CdS shells nearly lattice-matched to CdSe cores first developed to suppress photoluminescence blinking. Finally, we introduce a figure of merit useful to efficiently distinguish telegraphic noise from noise with a Gaussian distribution.

Influence of molecular imaging on patient selection for treatment intensification prior to salvage radiation therapy for prostate cancer: a post hoc analysis of the PROPS trial.

BACKGROUND: The impact of molecular imaging (MI) on patient management after biochemical recurrence (BCR) following radical prostatectomy has been described in many studies. However, it is not known if MI-induced management changes are appropriate. This study aimed to determine if androgen deprivation therapy (ADT) management plan is improved by MI in patients who are candidates for salvage radiation therapy. METHODS: Data were analyzed from the multicenter prospective PROPS trial evaluating PSMA/Choline PET in patients being considered for salvage radiotherapy (sRT) with BCR after prostatectomy. We compared the pre- and post-MI ADT management plans for each patient and cancer outcomes as predicted by the MSKCC nomogram. A higher percentage of predicted BCR associated with ADT treatment intensification after MI was considered as an improvement in a patient's management. RESULTS: Seventy-three patients with a median PSA of 0.38 ng/mL were included. In bivariate analysis, a positive finding on MI (local or metastatic) was associated with decision to use ADT with an odds ratio of 3.67 (95% CI, 1.25 to 10.71; p = 0.02). No factor included in the nomogram was associated with decision to use ADT. Also, MI improved selection of patients to receive ADT based on predicted BCR after sRT : the predicted nomogram 5-year biochemical-free survivals were 52.5% and 43.3%, (mean difference, 9.2%; 95% CI 0.8 to 17.6; p = 0.03) for sRT alone and ADT±sRT subgroups, while there was no statistically significant difference between subgroups before MI. CONCLUSIONS: PSMA and/or Choline PET/CT before sRT can potentially improve patient ADT management by directing clinicians towards more appropriate intensification.

Opioid use after uro-oncologic surgeries in time of opioid crisis.

INTRODUCTION: Recent literature emphasizes how overprescription and lack of guidelines contribute to wide variation in opioid prescribing practices and opioid-related harms. We conducted a prospective, observational study to evaluate opioid prescriptions among uro-oncologic patients discharged following elective in-patient surgery. METHODS: Patients who underwent four surgeries were included: open retropubic radical prostatectomy, robot-assisted radical prostatectomy, laparoscopic radical nephrectomy, and laparoscopic partial nephrectomy. The primary outcome was the dose of opioids used after discharge (in oral morphine equivalents [MEq]). Secondary outcomes included: opioid requirements for 80% of the patients, management of unused opioids, opioid use three months postoperative, opioid prescription refills, and guidance about opioid disposal. RESULTS: Sixty patients were included for analysis. Patients used a mean of 30 MEq (95% confidence interval 17.8-42.2) at home and 80% of the patients used 50 MEq or less. A mean of 40.4 MEq per patient was overprescribed. Fifty percent of the patients kept the remaining opioids at home, with only 20.0% returning them to their pharmacy. After three months, 5.0% of the patients were using opioids at least occasionally. Three patients needed a new opioid prescription. Forty percent reported having received information regarding management of unused opioids. CONCLUSIONS: We found 60% of opioids prescribed were unused, with half of our patients keeping these unused tablets at home. Our results suggest appropriate opioid prescription amounts needed for urological cancer surgery, with 80% of the patients using 50 MEq or less of morphine equivalents.

Synthesis, cytotoxicity, and haemolytic activity of chacotrioside lupane-type neosaponins and their germanicane-type rearrangement products.

The concise synthesis, via a stepwise glycosylation approach, of lupeol, betulin and betulinic acid O-glycosides bearing a chacotriosyl moiety at the C-3 position is described. All neosaponins as well as their rearrangement products of the germanicane-type were evaluated in vitro for their anticancer and haemolytic activities. Although betulinic acid and betulin 3beta-O-chacotriosides were neither cytotoxic nor haemolytic, their rearrangement products allobetulin and 28-oxoallobetulin 3beta-O-chacotriosides (9 and 10) exhibited a cytotoxicity profile up to fourfold superior to betulinic acid against human breast (MCF7) and prostate (PC-3) adenocarcinomas cell lines (IC(50)=10-18 microM). One important result was that only chacotriosides featuring non-polar functions at the C-28 position (6, 9 and 10) exerted a haemolytic activity against red blood cells.

Synthesis and cytotoxicity of bidesmosidic betulin and betulinic acid saponins.

The naturally occurring cytotoxic saponin 28-O-beta-d-glucopyranosylbetulinic acid 3beta-O-alpha-l-arabinopyranoside (3) was easily synthesized along with seven bidesmosidic saponins starting from the lupane-type triterpenoids betulin (1) and betulinic acid (2). As highlighted by the preliminary cytotoxicity evaluation against A549, DLD-1, MCF7, and PC-3 human cancer cell lines, the bidesmosidic betulin saponin 22a, bearing alpha-l-rhamnopyranoside moieties at both C-3 and C-28 positions, was determined to be a potent cytotoxic agent (IC(50) 1.8-1.9 microM).

Optimized transformation, overexpression and purification of S100A10.

As a member of the S100 protein family, S100A10 has already been purified. However, its purity, or even yield, have often not been reported in the literature. To facilitate future biophysical experiments with S100A10, we aimed to obtain it at a purity of at least 95% in a reasonably large amount. Here, we report optimized conditions for the transformation, overexpression and purification of the protein. We obtained a purity of 97% and performed stability studies by circular dichroism. Our data confirmed that the S100A10 obtained is suitable for experiments to be performed at room temperature up to several days.