Molecular pathways to CML stem cells.

Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), but it does not cure the disease. Many patients never achieve significant cytogenetic or molecular responses. Some develop resistance to the drug, while others are simply unable to tolerate it. Unfortunately, most will relapse if the drug is discontinued. This is particularly true in patients with advanced disease, who tend to develop resistance rapidly and are unlikely to achieve durable remission with single-agent tyrosine kinase inhibitor therapy. A growing body of evidence suggests that the reason imatinib does not cure CML is that it is unable to eradicate the leukemic stem cells (LSC). LSC are a tiny population of cancer cells with the capacity to recapitulate the disease. These quiescent cells have subverted properties of normal hematopoietic stem cells, allowing them to avoid apoptosis, evade innate immunity, renew themselves, and survive long term. Here, we review the studies that have identified the deregulated molecular pathways responsible for the generation of CML stem cells and discuss implications for therapy.

Factors influencing models of end-of-life care in nursing homes: results of a survey of nursing home administrators.

Approximately 20% of deaths in the United States occur in nursing homes. Dying nursing home residents have unique care needs, which historically have been inadequately addressed. The goal of this study was to determine what factors influence nursing home administrators' choice of model for end-of-life care in their facilities. Thirty nursing home administrators in the Denver, Colorado, metropolitan area were interviewed. The interview used open-ended questions about: facilities' end-of-life care programming and factors that influenced which model was used; scalar questions measuring administrators' attitudes about aspects of end-of-life care; and questions that assessed key demographic characteristics of participants. Twenty-nine of the 30 facilities included in this study reported contracting with hospice. Five were also in the process of creating in-house palliative care teams, and an additional five were negotiating with hospice agencies to dedicate beds for use as hospice units. For profit status, larger facility size, and shorter duration of administrator tenure were found to be associated with greater likelihood of considering implementation of a facility-based end-of-life care model. When asked about obstacles to providing quality end-of-life care, the majority of participants (n = 16) cited an educational deficit among physicians, staff, or the public as the most significant, while an additional seven cited staff shortages and turnover. These results suggest at least two potential avenues for change to improve end-of-life care in nursing homes: (1) educational efforts on the topics of end-of-life and palliative care among both practitioners, residents, and their families, and (2) creating incentives to improve staff recruitment and retention.