Background: Male-carriers of BRCA1/2 gene mutations have an increased risk of prostate cancer (PCa) with a more aggressive phenotype. Current screening-guidelines suggest the use of prostate-specific antigen (PSA) only among BRCA2 carriers. Female carriers have extensive guidelines that include imaging. Our objective was to test the prevalence of PCa among BRCA carriers and examine screening strategies, using PSA and multiparametric magnetic resonance imaging (mpMRI). Patients and methods: We recruited men aged 40e70 years with BRCA1/2 germline mutations and no prior history of prostate biopsy. All men underwent an initial round of screening which included PSA, and prostate mpMRI. PSA was considered elevated using an age-stratified threshold of !1 ng/ml for 40e50 years of age, !2 ng/ml for 50e60 years of age, and 2.5 ng/ml for 60e70 years of age. Men with elevated PSA and/or suspicious lesion on mpMRI were offered a prostate biopsy. PSA levels, MRI findings, PCa incidence, and tumor characteristics were evaluated. Decision curve analysis was used to compare screening strategies. Results: We recruited 188 men (108 BRCA1, 80 BRCA2), mean age 54 years (9.8). One hundred and ten (57%) had either elevated age-stratified PSA (75; 40%), a suspicious MRI lesion (67; 36%), or both (32; 17%). Of these, 92 (85%) agreed to perform a prostate biopsy. Sixteen (8.5%) were diagnosed with PCa; 44% of the tumors were classified as intermediateor high-risk disease. mpMRI-based screening missed only one of the cancers (6%), while age-stratified PSA would have missed five (31%). Decision curve analysis showed that mpMRI screening, regardless of PSA, had the highest net benefit for PCa diagnosis, especially among men younger than 55 years of age. We found no difference in the risk of PCa between BRCA1 and BRCA2 (8.3% versus 8.7%, P ¼ 0.91). Ninety percent had a Jewish founder mutation, thus the results cannot be generalized to all ethnic groups. Conclusions: PCa is prevalent among BRCA carriers. Age may affect screening strategy for PCa in this population. Young carriers could benefit from initial MRI screening. BRCA carriers aged older than 55 years should use PSA and be referred to mpMRI if elevated. Trial registration: ClinicalTrial.gov ID: NCT02053805.
BackgroundCatheter-Associated Hospital-Acquired Infections (HAI's) are caused by biofilm-forming bacteria. Using a novel approach, we generated anti-infective barrier on catheters by charging them with Nitric Oxide (NO), a naturally-produced gas molecule. NO is slowly released from the catheter upon contact with physiological fluids, and prevents bacterial colonization and biofilm formation onto catheter surfaces.Aims and methodsThe aim of the study was to assess the anti-infective properties of NO-charged catheters exposed to low concentration (up to 103 CFU/ml) of microbial cells in-vitro. We assessed NO-charged tracheal tubes using Pseudomonas aeruginosa, dialysis and biliary catheters using Escherichia coli, and urinary catheters using E. coli, Candida albicans or Enterococcus faecalis. Safety and tolerability of NO-charged urinary catheters were evaluated in a phase 1 clinical study in 12 patients. Six patients were catheterized with NO-charged catheters (NO-group), followed by 6 patients catheterized with regular control catheters (CT-group). Comparison of safety parameters between the study groups was performed.ResultsNO-charged tracheal, dialysis biliary and urinary catheters prevented P. aeruginosa, E. coli and C. albicans attachment and colonization onto their surfaces and eradicated corresponding planktonic microbial cells in the surrounding media after 24–48 hours, while E. faecalis colonization onto urinary catheters was reduced by 1 log compared to controls. All patients catheterized with an NO-charged urinary catheter successfully completed the study without experiencing NO-related AE's or serious AE's (SAE's).ConclusionThese data highlight the potential of NO-based technology as potential platform for preventing catheter-associated HAI's.
BackgroundProstate cancer screening among the general population is highly debatable. Nevertheless, screening among high-risk groups is appealing. Prior data suggests that men carrying mutations in the BRCA1& 2 genes may be at increased risk of developing prostate cancer. Additionally, they appear to develop prostate cancer at a younger age and with a more aggressive course. However, prior studies did not systematically perform prostate biopsies and thus cannot determine the true prevalence of prostate cancer in this population.MethodsThis will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40–70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention.DiscussionThe proposed research is highly translational and focuses not only on the clinical results, but on the future specimens that will be used to advance our understanding of prostate cancer patho-physiology. Most importantly, these high-risk germ-line mutation carriers are ideal candidates for primary and secondary prevention initiatives.Trial registrationClinicalTrials.gov: NCT02053805.
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