Cardiovascular (CV) health has emerged as an important consideration in patients with chronic myeloid leukemia (CML) because of improved prognosis. Indeed, the success of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has increased the focus on survivorship and late toxicity in oncological care. Survivorship issues in this population include CV disease prevention, given its prevalence in the general population. The introduction of BCR-ABL1 TKIs represented a unique concept of indefinite cancer therapy, only recently evolving to include “treatment-free remission.” Importantly, later-generation BCR-ABL1 TKIs have been associated with CV complications. Dasatinib has been associated with pleural/pericardial effusions and pulmonary hypertension, whereas nilotinib and ponatinib have been linked to the development of vascular occlusive events. There is currently a dearth of data with respect to the mechanisms of drug toxicities, the subsets of patients at risk, and prevention and treatment strategies to mitigate CV complications in patients with CML. Nevertheless, optimal patient CV risk assessment needs to become a more central tenet of patient care in CML. We propose several practical considerations for the practicing oncologist relative to the CV health of patients with CML, especially those on chronic TKI therapy.

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Haploinsufficiency of the melanocortin-4 receptor, the most common monogenetic obesity syndrome in humans, is associated with a reduction in autonomic tone, bradycardia, and incidence of obesity-associated hypertension. Thus, it has been assumed that melanocortin obesity syndrome may be protective with respect to obesity-associated cardiovascular disease. We show here that absence of the melanocortin-4 receptor (MC4R) in mice causes dilated cardiomyopathy, characterized by reduced contractility and increased left ventricular diameter. This cardiomyopathy is independent of obesity as weight matched diet induced obese mice do not display systolic dysfunction. Mc4r cardiomyopathy is characterized by ultrastructural changes in mitochondrial morphology and cardiomyocyte disorganization. Remarkably, testing of myocardial tissue from Mc4r−/− mice exhibited increased ADP stimulated respiratory capacity. However, this increase in respiration correlates with increased reactive oxygen species production – a canonical mediator of tissue damage. Together this study identifies MC4R deletion as a novel and potentially clinically important cause of heart failure.

We identified a genetic variant, an 8-residue appendage, of the α345 hexamer of collagen IV present in patients with glomerular basement membrane diseases, Goodpasture’s disease and Alport syndrome, and determined the long-awaited crystal structure of the hexamer. We sought to elucidate how variants cause glomerular basement membrane disease by exploring the mechanism of the hexamer assembly. Chloride ions induced in vitro hexamer assembly in a composition-specific manner in the presence of equimolar concentrations of α3, α4, and α5 NC1 monomers. Chloride ions, together with sulfilimine crosslinks, stabilized the assembled hexamer. Furthermore, the chloride ion–dependent assembly revealed the conformational plasticity of the loop-crevice-loop bioactive sites, a critical property underlying bioactivity and pathogenesis. We explored the native mechanism by expressing recombinant α345 miniprotomers in the cell culture and characterizing the expressed proteins. Our findings revealed NC1-directed trimerization, forming protomers inside the cell; hexamerization, forming scaffolds outside the cell; and a Cl gradient–signaled hexamerization. This assembly detail, along with a crystal structure, provides a framework for understanding hexamer dysfunction. Restoration of the native conformation of bioactive sites and α345 hexamer replacement are prospective approaches to therapeutic intervention.

Introduction In addition to shifting and expanding clinical responsibilities, rapidly evolving information and guidelines during the COVID-19 pandemic has made it difficult for health care workers (HCW) to synthesise and translate COVID-19 information into practice. This study evaluated whether a COVID-19-specific telemedicine education program (ECHO COVID) would impact health care workers’ self-efficacy and satisfaction in the management of patients with COVID-19. Methods A prospective mixed methods parallel-design study was conducted among ECHO COVID participants using pre-post questionnaires and a focus group discussion. Questionnaire results were examined for changes in health care workers’ self-efficacy and satisfaction. Focus group discussion data were analysed to explore health care workers’ experience in ECHO COVID and the context of their practice during the COVID-19 pandemic. Results 239 health care workers registered in ECHO COVID and 114 (47.7%) completed questionnaires and attended at least one ECHO COVID session. Median self-efficacy scores increased from 5 (IQR 4–6) to 6 (IQR 6–6) ( p < 0.0001), independent of profession, years in practice, age group, or practice environment. Participants were highly satisfied with ECHO COVID sessions with a median score of 4 (IQR 4–5). Focus group discussion data indicated that health care workers gained knowledge through ECHO COVID and revealed facilitators for ECHO COVID program success, including the transition to virtual care, the practicability of knowledge provided, and a ‘perspective from the trenches.’ Discussion This study demonstrated that a telemedicine education program aimed to support health care workers in managing patients with COVID-19 had a positive impact on health care workers’ self-efficacy and satisfaction. This impact was specifically mediated by the ECHO COVID program.