Estrogenic compounds such as bisphenol A (BPA) leach from plastics into food and beverage containers. Increased BPA exposure has been correlated with increased cardiovascular disease. To test the hypothesis that increased BPA exposure reduces cardiovascular remodeling, we chronically exposed C57bl/6n male mice to BPA and performed a myocardial infarction (MI). We measured cardiac function, as well as myeloid and cardiac fibroblast accumulation and activity. We found increased early death as well as increased cardiac dilation and reduced cardiac function in surviving BPA-exposed mice. Matrix metalloproteinase-2 (MMP2) protein and activity were increased 1.5-fold in BPA-exposed heart. BPA-exposed mice had similar neutrophil infiltration; however, monocyte and macrophage (MΦ) infiltration into the ischemic area was 5-fold greater than VEH mice potentially due to a 2-fold increase in monocyte chemoattractant protein-1. Monocyte and MΦ exposure to BPA in vitro in primary bone marrow cultures or in isolated peritoneal MΦ increased polarization to an activated MΦ, increased MMP2 and MMP9 expression 2-fold and activity 3-fold, and increased uptake of microspheres 3-fold. Cardiac fibroblasts (CF) differentiate to α-smooth muscle actin (αSMA) expressing myofibroblasts, migrate to the ischemic area and secrete collagen to strengthen the scar. Collagen and αSMA expression were reduced 50% in BPA-exposed hearts. Chronic in vivo or continuous in vitro BPA exposure ablated transforming growth factor beta-mediated differentiation of CF, reduced αSMA expression 50% and reduced migration 40% yet increased secreted MMP2 activity 2-fold. We conclude that chronic BPA exposure reduces the ability to successfully remodel after an MI by increasing MΦ-based inflammation and reducing myofibroblast repair function.
The COVID-19 pandemic has shifted oncology practices to prioritize patient safety while maintaining necessary treatment delivery. We obtained patient feedback on pandemic-based practices in our radiotherapy department to improve quality of patient care and amend policies as needed. We developed a piloted questionnaire which quantitatively and qualitatively assessed patients’ pandemic-related concerns and satisfaction with specific elements of their care. Adult patients who were treated at our Centre between 23 March and 31 May 2020, had initial consultation via telemedicine, and received at least five outpatient fractions of radiotherapy were invited to complete the survey by telephone or online. Relative frequencies of categorical and ordinal responses were then calculated. Fifty-three (48%) out of 110 eligible patients responded: 32 patients by phone and 21 patients online. Eighteen participants (34%) admitted to feeling anxious about hospital appointments, and only five (9%) reported treatment delays. Forty-eight patients (91%) reported satisfaction with their initial telemedicine appointment. The majority of patients indicated that healthcare workers took appropriate precautions, making them feel safe. Overall, all 53 patients (100%) reported being satisfied with their treatment experience during the pandemic. Patient feedback is needed to provide the highest quality of patient care as we adapt to the current reality.
Background: Best-practice guidelines recommend single-fraction (SFRT) instead of multi-fraction radiation therapy (MFRT) for uncomplicated symptomatic bone metastases. SFRT is comparable to MFRT in relieving pain, convenient for patients, and cost-effective. Patterns of practice in Canada reveal that SFRT is underused, with significant variability across the country. We audited SFRT use and studied factors that may influence treatment decisions at a large academic tertiary care center in Quebec, Canada. Methods: Patients who received radiotherapy for uncomplicated bone metastases between February 2014 and March 2015 were reviewed. Age, gender, primary histology, site of metastases and performance status were identified as potential factors affecting fractionation. These were explored by Fisher's test on univariate analysis and logistic regression for multivariate analysis. Retreatment rates were analyzed with cumulative incidence and compared with Gray's test. Results: 254 radiotherapy courses were administered to 165 patients, 85.4% of which were delivered using a single fraction of 8 Gy. Patients age less than 70 years and those with breast histology were more likely to receive MFRT (p = 0.04; p = 0.0046). Performance status (ECOG) was a significant predictor of fractionation because of high correlations between young age, breast histology, and ECOG status (p = 0.03). Follow-up was too short in 40% of patients to derive definitive conclusions on retreatment. Conclusions: In accordance with current guidelines, our audit confirms that use of SFRT in patients with uncomplicated bone metastases at our center is high. We identified that patient age, primary histology, and performance status influenced fractionation. Incorporation of this quality indicator into our performance dashboard will allow assessment of retreatment differences and other criteria that may also influence treatment choice.
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