External validation of the Memorial Sloan Kettering Cancer Center preoperative nomogram predicting lymph node invasion in a cohort of high-grade prostate cancer patients.

BACKGROUND: Commonly used preoperative nomograms predicting clinical and pathological outcomes in prostate cancer (PCa) patients have not been yet validated in high-grade only PCa patients. Our objective is to perform an external validation of the Memorial Sloan Kettering Cancer Center (MSKCC) preoperative nomogram as a predictor of lymph node invasion (LNI) in a cohort of high-grade PCa patients. METHODS: We included patients with high-grade PCa (Gleason ≥8) treated at our institution between 2011 and 2020 with radical prostatectomy and pelvic lymph node dissection without receiving neoadjuvant or adjuvant therapy. The area under the curve (AUC) of the receiver operator characteristic (ROC) was used to quantify the accuracy of the model to predict LNI. A calibration plot was used to evaluate the model's precision, and a decision curve analysis was computed to evaluate the net benefit associated with its use. This study was approved by our institution's ethics board. RESULTS: A total of 242 patients with a median age of 66 (60-71) years were included. LNI was observed in 70 (29%) patients with a mean of 16 (median = 15; range = 2-42) resected nodes. The MSKCC nomogram discriminative accuracy, as evaluated by the AUC-ROC was 79.0% (CI: [0.727-0.853]). CONCLUSION: The MSKCC preoperative nomogram is a good predictor of LNI and a useful tool associated with net clinical benefit in this patient population.

Decline in clinical severity of Paget's disease of bone: Comparison between a contemporary cohort and a historical cohort.

BACKGROUND: European and Australian studies have reported a decrease in the prevalence, incidence and clinical severity of Paget's disease of bone (PDB). There are no studies on the current clinical characteristics of PDB in Quebec, Canada. AIMS: The purpose of this study was to describe the characteristics of unrelated patients with PDB diagnosed after the year 2000 in our region and to compare them to a historical cohort diagnosed before 2000. METHODS: In this retrospective descriptive cohort study, socio-demographic data and clinical characteristics for the contemporary cohort were collected from electronic medical records of patients with PDB followed at our university hospital. For the historical cohort, the same data were collected from the research files of PDB participants in our research program. Inclusion criteria were: age > 18 years, having PDB diagnosed by a rheumatologist, and being followed in our hospital. Exclusion criteria were: having a relative with PDB participating in this study. Variables were reported as mean, standard deviation, frequency and percentage. Chi-square tests were used to compare categorical variables. Continuous values were compared with Wilcoxon-Mann-Whitney tests. Unadjusted p-values and adjusted p-values with the Bonferroni correction method were calculated. A p-value <0.05 was considered statistically significant. RESULTS: Among the 195 patients with PDB in the contemporary cohort, 53.3 % were men, 60.5 % had monostotic involvement, 14.2 % were symptomatic at diagnosis. In comparison to the historical cohort of 173 patients, patients in the contemporary cohort were older at diagnosis (68.7  10.7 vs. 58.5  10.1; p < 0.0001) and had less family history of PDB (13.8 % vs. 33.6 %; p = 0.0024). They also had lower total alkaline phosphatase levels at diagnosis (118.0 (85.0-184.0)) vs. 184.0 (115.0-312.0)); p = 0.0006), a lower pagetic bone number (1.0 (1.0-3.0) vs. 2.0 (1.0-5.0); p < 0.0001), lower pagetic bone fractures (6.7 % vs. 36.7 %; p = 0.0078) and lower bone deformities (13.0 % vs. 54.0 %; p < 0.0001). There was no significant difference for pagetic bone pain (52.0 % vs. 52.6 %; p = 1.0000), percentage of patients who had orthopedic surgery related to PDB complications (8.8 % vs. 28.6 %; p = 1.0000), secondary osteoarthritis (43.0 % vs. 51.6 %; p = 1.0000), and hearing impairment (51.9 % vs. 61.1 %; p = 0.1000). CONCLUSION: The contemporary cohort is characterized by an older age at diagnosis, a majority of monostotic disease and fewer complications of PDB. This decline in clinical severity of PDB in Quebec is consistent with studies reported in other countries.

Effects of omega-3 fatty acids supplementation on perioperative blood loss and complications after radical prostatectomy.

BACKGROUND AND AIMS: Many dietary supplements, including omega-3 fatty acids (ω3), are suspected to affect blood coagulation and platelet function. Despite no clinical evidence, discontinuation is recommended before radical prostatectomy. However, long-chain ω3 (LCω3) appear beneficial against prostate cancer progression. Here, we aim to determine the effect of LCω3 supplements on perioperative bleeding, hemoglobin, platelets, and postoperative complications after radical prostatectomy. METHODS: This is a planned exploratory analysis of 130 patients diagnosed with prostate cancer grade group 2 or greater enrolled in a randomized controlled trial (NCT02333435) testing the effects of LCω3, on prostate cancer biological and pathological outcomes at radical prostatectomy as main outcomes. The LCω3 intervention (MAG-EPA 3 g daily) or equivalent placebo was given 4-10 weeks prior to radical prostatectomy. An intention-to-treat analysis approach was used with bi-variate statistical testing of bleeding and complications outcomes. We also estimated the difference between groups using linear regression and non-parametric quantile regression models. All models were adjusted for confounding variables selected on clinical relevance. RESULTS: We found no clinically significant effect of LCω3 versus placebo on perioperative bleeding, laboratory tests or postoperative complications. In contrast, as expected, we found a significant increase in perioperative bleeding in open retropubic radical prostatectomy compared to robot-assisted radical prostatectomy (adjusted difference 115.8 mL, p = 0.04). CONCLUSIONS: Our results suggest that ω3 supplements can be safely taken before radical prostatectomy without increasing surgical bleeding risk. These findings are relevant since ω3 may beneficially affect prostate cancer evolution.

A Sequential Two-Step Cell-Based Assay Predicts Immunosuppression-Related Adverse Events.

Immunosuppressants are associated with serious and often life-threatening adverse effects. To optimize immunotherapy, a tool that measures the immune reserve is necessary. We validated that a cell-based assay that measures TNF-α production by CD14+16+ intermediate monocytes following stimulation with EBV peptides has high sensitivity for the detection of over-immunosuppression (OIS) events. To develop a sequential, two-step assay with high specificity, we used PBMCs from kidney recipients (n = 87). Patients were classified as cases or controls, according to the occurrence of opportunistic infection, recurring bacterial infections, or de novo neoplasia. Patients who tested positive in the first step were randomly allocated to a training or a testing set for the development of the second step. In the discovery phase, an assay based on the examination of early mature B (eBm5) cells was able to discriminate OIS patients from controls with a specificity of 88%. The testing set also revealed a specificity of 88%. The interassay coefficient of variability between the experiments was 6.1%. Stratified analyses showed good diagnostic accuracy across tertiles of age and time posttransplant. In the adjusted model, the risk of OIS was more than 12 times higher in patients classified as positive than in those who tested negative (adjusted hazard ratio, 12.2; 95% confidence interval: 4.3-34.6). This sequential cell-based assay, which examines the monocyte and eBm5 cell response to EBV peptides, may be useful for identifying OIS in immunosuppressed patients.

First-Degree Relatives Screening of Patients with Bicuspid Aortic Valve: Effectiveness and Feasibility in Pediatric Cardiology Daily Practice.

Bicuspid aortic valve (BAV) is the most common congenital heart disease. Since heritability is suspected, actual guidelines recommend to perform an echocardiographic assessment for first-degree relatives (FDR) of patient with BAV. This study aimed to assess the effectiveness and the feasibility of the current guidelines for the screening of FDR of patient with BAV in a pediatric cardiology daily practice. Consecutive patients with BAV and their FDR were prospectively included from January 2015 to March 2018 at Centre Hospitalier Universitaire de Laval, Quebec City (Canada). Data were retrospectively collected and analyzed. A total of 713 FDR of 213 consecutives index cases [median age: 11 (6-20) years] were studied. Up to 32 (6.6%) FDR had a BAV and 26 (5.4%) had an aortic valve dysfunction. A total of 14 (2.9%) FDR had an ascending aorta dilatation according to Z-score including 6 (1.2%) patients with an ascending aorta ≥ 45 mm. No statistically significant differences regarding BAV, aortic valve dysfunction and ascending aorta dilatation prevalence were identified between generations. Screening was done in 482 (67.6%), prescribed but not done in 134 (19%), not prescribed in 92 (13%) and declined in 5 (1%) FDR. The prevalence of BAV in FDR was similar to prospective adult studies and supports actual guidelines in pediatric cardiology practice. Ascending aorta dilatation was rare in our young population. Exhaustiveness and additional burden to implement current guidelines remain a challenge in daily practice.