The heart is known for its resistance to cancer. Although different conjectures have been proposed to explain this phenomenon, none has been tested. We propose that the heart microenvironment may exert anti-cancer properties. So, our objective was to test the anti-oncogenic potential of cardiac-derived extracellular vesicles (EVs).For that EVs secreted by cardiosphere-derived cells (CDCs, heart progenitor cells) were tested in vitro on fibrosarcoma HT1080. In vivo models comprised the xenograft HT1080 fibrosarcoma in athymic mice (n=35), and spontaneous acute lymphocyte leukemia in old rats (n=44). CDC-EVs were compared with two control groups: EVs secreted by bone-marrow derived mesenchymal stem cells (MSC-EVs) and phosphate-buffered saline (PBS).Injection of CDC-EVs led to a 2.5-fold decrease of fibrosarcoma growth in mice (p<0.01 and p<0.05 for human and rat EVs, respectively) vs PBS group. The effect was associated with 2-fold decrease of tumor cells proliferation (p<0.001) and 1.5-fold increase of apoptosis (p<0.05) in CDC-EV vs PBS mice. Salutary changes in tumor gene and protein expression were observed in CDC-EV animals. CDC-EVs reduced tumor vascularization compared with PBS (p<0.05) and MSC-EVs (p<0.01). Moreover, CDC-EVs increased leukemia-free survival (p<0.05) in old rats vs PBS. MiR-146, highly enriched in CDC-EVs, may be implicated in part of the observed effects. In conclusion, this study presents the first evidence that ties together the long-recognized enigma of the “heart immunity to cancer” with an antioncogenic effect of heart-derived EVs. These findings open up cancer as a new therapeutic target for CDC-EVs.
Objectives
Atrial functional mitral regurgitation (AFMR) is a subtype of functional mitral regurgitation due to longstanding atrial fibrillation (AF) or heart failure with preserved ejection fraction. The variation in AFMR' definition and the common mode of treatment described in the literature remain unknown.
Methods
We performed a scoping review of studies that surgically treated AFMR to characterize the existing variability in the definition of AFMR, the type of operations performed for AFMR valvulopathy, and the treatment for the chronic AF. We searched Medline, EMBASE, Cochrane Library, Scopus, and Web of Science since their inceptions for studies of patients affected by AFMR and surgically treated for their valvulopathy.
Results
Twelve studies (n = 494 patients) met eligibility criteria. All studies excluded patients with signs of left ventricular (LV) dysfunction, but the way additional parameters were used to define AFMR at a more granular level varied across studies: nine studies (75%) used the presence of AF to define their AFMR cohorts, with five (41.2%) requiring a history of AF of >1 year; additionally, the threshold values for the LV ejection fraction differed (45%–55%). Isolated mitral annuloplasty was performed in 96.2% of patients. Broad variability was detected in the proportion of patients undergoing the Cox‐Maze procedure (range, 17.8%–79.5%), pulmonary vein isolation (0.0%–66.7%), and left atrial appendage ligation (0.0%–100.0%).
Conclusions
AFMR remains variably defined in surgical studies, making comparisons across studies difficult. Mitral annuloplasty was most commonly performed. The proportion of AFMR patients undergoing concomitant procedures for AF varied substantially.
PURPOSE: To understand how patients and providers weigh the risks and benefits of long-term opioid therapy (LTOT) for cancer pain. METHODS: Researchers used VA approved audio-recording devices to record interviews. ATLAS t.i., a qualitative analysis software, was used for analysis of transcribed interview data. Participants included 20 Veteran patients and 20 interdisciplinary providers from primary care– and oncology-based practice settings. We conducted semistructured interviews and analyzed transcripts used thematic qualitative methods. Interviews explored factors that affect decision making about appropriateness of LTOT for cancer related pain. We saturated themes for providers and patients separately. RESULTS: Factors affecting patient decision-making included influence from various information sources, persuasion from trusted providers, and sometimes deferral of the decision to their provider. Relative prioritization of pain management as the focal patient concern varied with some patients describing comparatively more fear of chemotherapy than opioid analgesics, comparatively more knowledge of opioids in relation to other drugs;patients expressed a preference to spend the limited time they have with their oncologist discussing cancer treatment rather than opioid use. Factors affecting provider decision making included prognosis, patient goals, patient characteristics, and provider experience and biases. Providers differed in how they weigh the relative importance of alleviating pain or avoiding opioids in the face of treating patients with cancer and histories of substance abuse. CONCLUSION: Divergent perspectives on factors need to be considered when weighing risks and benefits. Policies and interventions should be designed to reduce variation in practice to promote equal access to adequate pain management. Improved shared decision-making initiatives will take advantage of patient decision-making factors and priorities.
PURPOSE Seven major palliative care (PC) centers in India were mentored through the Palliative Care—Promoting Assessment and Improvement of the Cancer Experience (PC-PAICE) by US and Australian academic institutions to implement a quality improvement (QI) project to improve the accessibility and quality of PC at their respective centers. The objective was to evaluate the experiences of teams in implementing QI methods across diverse geographical settings in India. METHODS A quota sampling approach was used to elicit perspectives of local stakeholders at each site. The Consolidated Framework for Implementation Research informed development of a semistructured interview guide. Analysis leveraged deductive and inductive approaches. RESULTS We interviewed 44 participants (eight organizational leaders, 12 clinical leaders, and 24 team members) at seven sites and identified five themes. (1) Implementing QI methods enabled QI teams to think analytically to solve a complex problem and to identify resources. (2) Developing a problem statement by identifying specific gaps in patient care fostered team collaboration toward a common goal. (3) Making use of QI tools (eg, A3 process) systematically provided a new, straightforward QI toolkit and improved QI teams' conceptual understanding. (4) Enhancing stakeholder engagement allowed shared understanding of QI team members' roles and processes and shaped interventions tailored to the local context. (5) Designing less subjective processes for patient care such as assessment scales to identify patient's symptomatic needs positively changed work practices and culture. CONCLUSION Engaging and empowering multiple stakeholders to use QI methods facilitated the expansion and improvement of PC and cancer services in India. PC-PAICE demonstrated an efficient, effective way to apply QI methods in an international context. The impact of PC-PAICE is being magnified by developing a cadre of Indian QI leaders.
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