Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the NF1 tumor suppressor gene. Neurofibromin is encoded by NF1 and functions as a negative regulator of Ras activity. NF1 patients develop renal artery stenosis and arterial occlusions resulting in cerebral and visceral infarcts. Further, NF1 patients develop vascular neurofibromas where tumor vessels are invested in a dense pericyte sheath. Although it is well established that aberrations in Ras signaling lead to human malignancies, emerging data generated in genetically engineered mouse models now implicate perturbations in the Ras signaling axis in vascular smooth muscular cells (VSMCs) as central to the initiation and progression of neointimal hyperplasia and arterial stenosis. Despite these observations, the function of neurofibromin in regulating VSMC function and how Ras signals are terminated in VSMCs is virtually unknown. Utilizing VSMCs harvested from Nf1+/- mice and primary human neurofibromin-deficient VSMCs, we identify a discrete Ras effector pathway, which is tightly regulated by neurofibromin to limit VSMC proliferation and migration. Thus, these studies identify neurofibromin as a novel regulator of Ras activity in VSMCs and provide a framework for understanding cardiovascular disease in NF1 patients and a mechanism by which Ras signals are attenuated for maintaining VSMC homeostasis in blood vessel walls.

Genetic inactivation of tumor suppressor genes initiates human cancers. However, interaction of accessory cells with the tumor-initiating cell within the microenvironment is often required for tumor progression. This paradigm is relevant to understanding neurofibroma development in neurofibromatosis type I patients. Somatic inactivation of the Nf1 tumor suppressor gene, which encodes neurofibromin, is necessary but not sufficient to initiate neurofibroma development. In contrast, neurofibromas occur with high penetrance in mice in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant (Nf1+/-) microenvironment. Neurofibromas are highly vascularized, and recent studies suggest that Nf1+/- mice have increased angiogenesis in vivo. However, the function of neurofibromin in human endothelial cells (ECs) and the biochemical mechanism by which neurofibromin regulates neoangiogenesis are not known. Utilizing Nf1+/- mice, primary human ECs and endothelial progenitor cells harvested from NF1 patients, we identified a discrete Ras effector pathway, which alters the proliferation and migration of neurofibromin-deficient ECs in response to neurofibroma-derived growth factors both in vitro and in vivo. Thus, these studies identify a unique biochemical pathway in Nf1+/- ECs as a potential therapeutic target in the neurofibroma microenvironment.

BACKGROUND: Ineffective transitions of care continue to be a source of risk for patients. Although there has been widespread implementation of electronic medical record (EMR) systems, little is currently known about hospitalists' and primary care providers' (PCPs) direct communication preferences at discharge using messaging capabilities in a shared EMR system. OBJECTIVE: We examined how hospitalists and PCPs with a shared EMR prefer to directly communicate at the time of hospital discharge by identifying preferred modes, information prioritization, challenges, facilitators, and proposed solutions. DESIGN: A sequential, explanatory mixed methods study with surveys and semi-structured interviews. PARTICIPANTS: Thirty-eight academic hospitalists and 63 PCPs working in outpatient clinics in a single safety net hospital system with a shared EMR. MAIN APPROACH: Descriptive statistics were used to analyze survey responses. Interviews were analyzed using immersion/crystallization and a mixture of inductive and deductive thematic analysis. KEY RESULTS: PCPs preferred direct communication at discharge through a message within the EMR while hospitalists preferred a message within the EMR and email. Qualitative results identified key themes related to patient care and direct communication: value of direct communication, safety, social determinants of health, and clinical judgment. Both groups prioritized direct communication for high-risk medications, pending and follow-up studies, and high-risk patients that hospitalists were concerned about. Overall, both hospitalists and PCPs reported that ensuring patient safety, flagging patients with social challenges, and expressing concerns about patients based on clinical judgment were key communication priorities.CONCLUSIONS: Hospitalists and primary care providers report considerable overlap in preferences for direct communication at the time of hospital discharge through a shared EMR. Specifically, both groups reported similar concerns regarding patient safety and continuity during transitions. Direct messaging within the EMR could enable "closed loop" communication that helps ensure safe transitions of care for high-risk patients.

BACKGROUND Research by hospitalists may aid the evolution of hospital medicine into an academic specialty. OBJECTIVE To describe the factors associated with research and publication activities among hospitalists and describe trends in hospitalist‐led publications. METHODS We surveyed members of the Society of Hospital Medicine in June 2012 and conducted univariate analyses on their responses to determine predictors of successful authorship and to describe factors associated with research engagement. We searched PubMed from the database inception to October 2013 for publications with “hospitalist” or “hospital medicine” affiliated authors. Original research articles were reviewed for methodology and funding sources. RESULTS Of the 645 respondents (5.8% response rate), 277 (43%) had authored peer‐reviewed publications, 126 (19%) had access to mentorship, and 68 (11%) reported funding support. There were 213 (33%) who were engaged in research, with the majority conducting quality improvement (QI) research (n = 152, 24%). Completion of a fellowship, pediatrics training, the presence of a mentor, funding, and >25% protected time for research were each individually associated with an increased likelihood of authoring publications. Hospitalist‐led publications in PubMed have been increasing from 36 in 2006 to 179 in the first 10 months of 2013. Of the original research publications (n = 317), the majority were clinical (n = 129, 41%), and 58 (18%) were QI. Thirty‐nine (22%) authors reported funding support. CONCLUSIONS Peer‐reviewed publications by hospitalists are increasing, suggesting the academic maturation of hospital medicine. Provision of mentorship for hospitalists specifically in QI and guidance toward funding resources may assist in supporting this trend. Journal of Hospital Medicine 2014;9:148–154. © 2014 Society of Hospital Medicine