Aortic valve stenosis is one of the most common valve diseases in the world for which there is currently no pharmacological treatment to prevent or halt disease progression. Recent genetic research has demonstrated a causal association between elevated blood levels of lipoprotein (a) (Lp (a)) and aortic valve calcification, however, the mechanisms by which Lp (a) contributes to aortic valve calcification and stenosis, is unknown. In the present study, we aimed at determining Lp (a)-induced changes in human aortic valve interstitial cells using an integrated bioinformatics approach. The Lp (a)-induced cellular pathways were analysed using microarray gene expression and proteomic data from non-stenotic human aortic valve interstitial cells. Lp (a) treatment induced osteogenic differentiation, extracellular remodeling, extracellular vesicles biogenesis, and apoptosis of human aortic valve interstitial cells. In particular, the Wnt/ β-catenin signalling pathway, a known calcification pathway contributing to aortic valve stenosis, was differentially expressed compared to non-treated cells. Lp (a) also induced the expression of 14-3-3 proteins known to regulate various signalling pathway relevant to aortic valve disease. Elucidating the mechanisms and molecular players that Lp (a) induces in the early stages of the disease to initiate aortic valve calcification could provide insight into potential pharmacological targets for the treatment of this debilitating disease.

Quality Indicators (QIs), including the breast-conserving surgery (BCS) rate, were published by the European and American Breast Cancer Societies and this study assesses these in a Canadian population to look for opportunities to de-escalate surgery. A total of 2311 patients having surgery for unilateral, unifocal breast cancer between 2013 and 2017 were identified and BCS QIs calculated. Reasons for mastectomy had been prospectively collected with synoptic operative reporting. Our BCS rate for invasive cancer < 3 cm was 77.1%, invasive cancer < 2 cm was 84.1%, and DCIS < 2 cm was 84.9%. There was no statistically significant change in BCS rates over a five-year period, but there was a reduction in contralateral prophylactic mastectomies (CPM) from 28% in 2013 to 16% in 2017 (p < 0.001). Trend analysis looking at tumour size and medical need for mastectomy indicated that 80% of patients at our centre would be eligible for BCS with tumour cut off of 2.5 cm. Our institution met American but not European QI standards for BCS rates, potentially indicating a difference in patient demographics compared to Europe. Our results support the understanding that BCS rates are influenced by multiple factors and are challenging to compare across jurisdictions. CPM rates may offer a more actionable opportunity to de-escalate surgery for breast cancer.

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Background: Variety of tools has been used to teach history-taking skills to novice learners. Standardized Patient (SP) is the gold standard for medical education. We hypothesized that the use of online simulation platforms Cy-berPatient™ (CP) is as effective as SP. Methods: In this prospective randomized controlled trial study, the educational effectiveness of CP was compared to SP in improving history taking skills. Twenty-two incoming students at University of British Columbia (UBC) were randomly divided in to two (SP and CP) groups. SP Group (n = 11) practiced their history taking skills with the standardized patients and CP Group (n = 11)-with CyberPatients. The content for both groups included 3 cases of GI pathology and the study time was 60 minutes. Assessment method included Objective Structured Clinical Examination (OSCE) before and after interventions. Data were analysed in a two-way between/within ANOVA and Wald test was used to deal with the violation of the ANOVA assumptions. Economic benefits were assessed as Cost-effectiveness (calculated as Cost/Effect Ratio) and Cost-Value Proposition (Cost-Vale Relationship). Results: Results of this study indicated that both groups had significant (SP group p = 0.006 and CP group p = 0.0001) improvement in the knowledge domain of history taking. The history taking knowledge variable in both groups manifested a significant main effect of time indicating that students did better after interventions, F (1, 15.1) = 10.5, p = 0.011. The groups performed at a similar level after intervention. Moreover, results show that the use of the CP is more cost-effective and has a better cost/value proposition for medical education. Conclusion: We conclude that CyberPatient™ is as effective as using standardized patients in delivery of practical knowledge for novice medical students, however, CyberPatient™ is more economically rewarding.

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