Extracellular SPARC increases cardiomyocyte contraction during health and disease

Secreted protein acidic and rich in cysteine (SPARC) is a non-structural extracellular matrix protein that regulates interactions between the matrix and neighboring cells. In the cardiovascular system, it is expressed by cardiac fibroblasts, endothelial cells, and at lower levels by ventricular cardiomyocytes. SPARC expression levels are increased upon myocardial injury and also during hypertrophy and fibrosis. We have previously shown that SPARC improves cardiac function after myocardial infarction by regulating post-synthetic procollagen processing, however whether SPARC directly affects cardiomyocyte contraction is still unknown. In this study we demonstrate a novel inotropic function for extracellular SPARC in the healthy heart as well as in the diseased state after myocarditis-induced cardiac dysfunction. We demonstrate SPARC presence on the cardiomyocyte membrane where it is co-localized with the integrin-beta1 and the integrin-linked kinase. Moreover, extracellular SPARC directly increases cardiomyocyte cell shortening ex vivo and cardiac function in vivo, both in healthy myocardium and during coxsackie virus-induced cardiac dysfunction. In conclusion, we demonstrate a novel inotropic function for SPARC in the heart, with a potential therapeutic application when myocyte contractile function is diminished such as that caused by a myocarditis-related cardiac injury

Study protocol of KLIMOP: a cohort study on the wellbeing of older cancer patients in Belgium and the Netherlands

<p>Abstract</p> <p>Background</p> <p>Cancer is mainly a disease of older patients. In older cancer patients, additional endpoints such as quality of survival and daily functioning might be considered equally relevant as overall or disease free survival. However, these factors have been understudied using prospective designs focussing on older cancer patients. Therefore, this study will focus on the impact of cancer, ageing, and their interaction on the long-term wellbeing of older cancer patients.</p> <p>Methods/Design</p> <p>This study is an observational cohort study. We aim to recruit 720 cancer patients above 70 years with a new diagnosis of breast, prostate, lung or gastrointestinal cancer and two control groups: one control group of 720 patients above 70 years without a previous diagnosis of cancer and one control group of 720 cancer patients between 50 - 69 years newly diagnosed with breast, prostate, lung or gastrointestinal cancer. Data collection will take place at inclusion, after six months, after one year and every subsequent year until death or end of the study. Data will be collected through personal interviews (consisting of socio-demographic information, general health information, a comprehensive geriatric assessment, quality of life, health locus of control and a loneliness scale), a handgrip test, assessment of medical records, two buccal swabs and a blood sample from cancer patients (at baseline). As an annex study, caregivers of the participants will be recruited as well. Data collection for caregivers will consist of a self-administered questionnaire examining depression, coping, and burden.</p> <p>Discussion</p> <p>This extensive data collection will increase insight on how wellbeing of older cancer patients is affected by cancer (diagnosis and treatment), ageing, and their interaction. Results may provide new insights, which might contribute to the improvement of care for older cancer patients.</p

General practitioners' considerations when deciding whether to initiate end-of-life conversations: a qualitative study

Background: End-of-life discussions often are not initiated until close to death, even in the presence of life-limiting illness or frailty. Previous research shows that doctors may not explicitly verbalize approaching end-of-life in the foreseeable future, despite shifting their focus to comfort care. This may limit patients' opportunity to receive information and plan for the future. General Practitioners (GPs) have a key role in caring for increasing numbers of patients approaching end-of-life. Objective: To explore GPs' thought processes when deciding whether to initiate end-of-life discussions. Methods: A qualitative approach was used. We purposively recruited 15 GPs or GP trainees from South-East Queensland, Australia, and each participated in a semi-structured interview. Transcripts were analyzed using inductive thematic analysis. Results: Australian GPs believe they have a responsibility to initiate end-of-life conversations, and identify several triggers to do so. Some also describe caution in raising this sensitive topic, related to patient, family, cultural and personal factors. Conclusions: These findings enable the development of approaches to support GPs to initiate end-of-life discussions that are cognizant both of GPs' sense of responsibility for these discussions, and factors that may contribute to caution initiating them, such as anticipated patient response, cultural considerations, societal taboos, family dynamics and personal challenges to doctors