were not informed at time of 2728 filing, for reasons reported by providers as follows: 42.1% unassessed, 30.4% medically unfit, 16.9% unsuitable due to age, 3.1% psychologically unfit and 1.5% declined counsel. Older, obese, uninsured, Medicaidinsured and patients at for-profit centers were more likely to be unassessed. Women were more likely to be reported as unsuitable due to age, medically unfit and declined, and African Americans as psychologically unfit. Uninformed patients had a 53% lower rate of ATT, a disparity persisting in the subgroup of uninformed patients who were unassessed. Disparities in ATT may be partially explained by disparities in provision of transplant information; dialysis centers should ensure this critical intervention is offered equitably.
The serine/threonine kinase AKT and its downstream mediator mammalian target of rapamycin (mTOR) are activated in lung adenocarcinoma, and clinical trials are under way to test whether inhibition of mTOR is useful in treating lung cancer. Here, we report that mTOR inhibition blocked malignant progression in K-ras(LA1) mice, which undergo somatic activation of the K-ras oncogene and display morphologic changes in alveolar epithelial cells that recapitulate those of precursors of human lung adenocarcinoma. Levels of phospho-S6(Ser236/235), a downstream mediator of mTOR, increased with malignant progression (normal alveolar epithelial cells to adenocarcinoma) in K-ras(LA1) mice and in patients with lung adenocarcinoma. Atypical alveolar hyperplasia, an early neoplastic change, was prominently associated with macrophages and expressed high levels of phospho-S6(Ser236/235). mTOR inhibition in K-ras(LA1) mice by treatment with the rapamycin analogue CCI-779 reduced the size and number of early epithelial neoplastic lesions (atypical alveolar hyperplasia and adenomas) and induced apoptosis of intraepithelial macrophages. LKR-13, a lung adenocarcinoma cell line derived from K-ras(LA1) mice, was resistant to treatment with CCI-779 in vitro. However, LKR-13 cells grown as syngeneic tumors recruited macrophages, and those tumors regressed in response to treatment with CCI-779. Lastly, conditioned medium from primary cultures of alveolar macrophages stimulated the proliferation of LKR-13 cells. These findings provide evidence that the expansion of lung adenocarcinoma precursors induced by oncogenic K-ras requires mTOR-dependent signaling and that host factors derived from macrophages play a critical role in adenocarcinoma progression.
IntroductionAccording to the World Health Organization (WHO), burns result in the loss of approximately 18 million disability adjusted life years (DALYs) and more than 250,000 deaths each year, more than 90% of which are in low- and middle-income countries (LMICs). The epidemiology of these injuries, especially in the WHO-defined African Region, has yet to be adequately defined.MethodsWe performed a systematic review of the literature regarding the epidemiology of thermal, chemical, and electrical burns in the WHO-defined African Region. All articles indexed in PubMed, EMBASE, Web of Science, Global Health, and the Cochrane Library databases as of October 2015 were included.ResultsThe search resulted in 12,568 potential abstracts. Through multiple rounds of screening using criteria determined a priori, 81 manuscripts with hospital-based epidemiology as well as eleven manuscripts that included population-based epidemiology were identified. Although the studies varied in methodology, several trends were noted: young children appear to be at most risk; most individuals were burned at home; and hot liquids and flame are the most common aetiologies.DiscussionWhile more population-based research is essential to identifying specific risk factors for targeted prevention strategies, our review identifies consistent trends for initial efforts at eliminating these often devastating and avoidable injuries.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.