Structural and Molecular Mechanisms of Cytokine-Mediated Endocrine Resistance in Human Breast Cancer Cells.

Human breast cancers that exhibit high proportions of immune cells and elevated levels of pro-inflammatory cytokines predict poor prognosis. Here, we demonstrate that treatment of human MCF-7 breast cancer cells with pro-inflammatory cytokines results in ERα-dependent activation of gene expression and proliferation, in the absence of ligand or presence of 4OH-tamoxifen (TOT). Cytokine activation of ERα and endocrine resistance is dependent on phosphorylation of ERα at S305 in the hinge domain. Phosphorylation of S305 by IKKß establishes an ERα cistrome that substantially overlaps with the estradiol (E2)-dependent ERα cistrome. Structural analyses suggest that S305-P forms a charge-linked bridge with the C-terminal F domain of ERα that enables inter-domain communication and constitutive activity from the N-terminal coactivator-binding site, revealing the structural basis of endocrine resistance. ERα therefore functions as a transcriptional effector of cytokine-induced IKKß signaling, suggesting a mechanism through which the tumor microenvironment controls tumor progression and endocrine resistance.

Atypical Molecular Features of Pediatric Tectal Glioma: A Single Institutional Series.

We present 4 children (diagnosed between 1 and 8 y, 3 females and 1 male) with molecularly distinct tectal gliomas (2 KRAS mutant, 1 EGFR mutant, 1 SRGAP3-RAF-1 fusion) that contributes to the growing literature of this uncommonly biopsied tumor. The patient with EGFR R222C mutation had a more severe course, earlier diagnosis, subsequent leptomeningeal metastatic disease, required more aggressive therapies, and died 9 years after diagnosis. Patients with KRAS mutations and SRGAP3-RAF-1 fusion had a more indolent course. Our series expands the molecular phenotype of tectal glioma with the potential for leptomeningeal dissemination. Future studies on establishing genotypic/phenotypic correlation from those who undergo biopsy are needed.

Hospital-Community Partnerships to Aid Transitions for Older Adults: Applying the Care Transitions Framework.

This study examined the implementation and hospitalwide scaling of a community-based transitional care program to reduce readmissions among adults 65 years or older. Our analysis was guided by the Care Transitions Framework and was based on semistructured interviews with program implementers to identify intervention successes, barriers, and outcomes beyond reducing readmissions. Such outcomes included the program's critical role in providing a safety net and transition to more advanced care, and redefining intervention success from more patient-centered perspectives.

Congenital CMV associated with diaphragm dysfunction: a rare cause of tachypnoea.

A late preterm infant with intrauterine growth restriction developed respiratory distress, tachypnoea and hypoxia after birth, requiring supplemental oxygen. Chest radiographs demonstrated persistent elevation of the right hemidiaphragm. Chest ultrasound initially demonstrated symmetrical bilateral diaphragm motion, but subsequent ultrasounds showed asymmetrical excursion with weaker movement of the right hemidiaphragm. Placental pathology demonstrated chronic infectious villitis secondary to cytomegalovirus (CMV), and subsequent CMV testing on the infant was positive. The infant was microcephalic and head imaging revealed intracranial calcifications, consistent with congenital CMV infection.CMV is the most common congenital infection and has a wide array of clinical manifestations. This report highlights the rarely described association between congenital CMV infection and respiratory distress due to underlying diaphragm dysfunction. In neonates with respiratory distress and features of congenital CMV infection, clinicians should have a high index of suspicion for diaphragm dysfunction.

Physician Engagement With Metrics in Lean Primary Care Transformation.

OBJECTIVE: Data and metrics play important roles in quality and process improvement efforts. For one specific process improvement method, Lean or Lean health care, data and metrics are central components, allowing users to identify areas that need improvement and to assess the degree to which improvements have been realized. This article explores the role that metrics and measurement played in a wide-reaching "Lean"-based continuous quality improvement effort carried out in the primary care departments of a large, ambulatory care health care organization. METHODS: This article is based on qualitative data collected through in-depth interviews with physicians, staff, and health care leaders. RESULTS: Suggestions for improving the ways that metrics may be optimally used, presented, and approached while carrying out health care improvement efforts include having accurate and compelling data throughout the improvement process, ensuring that metrics are professionally meaningful to physicians, and presenting metrics in a manner that increases the likelihood that they will be digested and ultimately used to improve health care. CONCLUSIONS: Effective strategies for selecting and presenting metrics to practicing physicians are an important part of a successful quality improvement effort.

Nurses' Perspectives on Lean Redesigns to Patient Flow and Inpatient Discharge Process Efficiency.

As hospitals around the world increasingly face pressure to improve efficiency, "Lean" process improvement has become a popular approach to improving patient flow. In this article, we examine nurses' perspectives on the implementation of Lean redesigns to the inpatient discharge process. We found that nurses experienced competing demands and tensions related to their time and professional roles and responsibilities as a result of Lean. Four main themes included (a) addressing the needs of individual patients, while still maintaining overall patient flow; (b) meeting discharge efficiency targets while also achieving high patient satisfaction scores; (c) "wasting time" to save time; and (d) the "real" work of providing clinical care versus the "Lean" work of process improvement. Our findings highlight the importance of soliciting hospital nurses' perspectives when implementing Lean process improvements to improve efficiency and patient flow.

Implementing a Lean Management System in Primary Care: Facilitators and Barriers From the Front Lines.

BACKGROUND: Although Lean management techniques are increasingly used in health care to improve quality and reduce costs, lessons about how to successfully implement this approach on the front lines of care delivery are not well documented. In this study, we highlight key facilitators and barriers to implementing Lean among frontline primary care providers. METHODS: This case study took place at a large, ambulatory care delivery system serving nearly 1 million patients. In-depth interviews were conducted with primary care physicians, staff, and administrators to identify key factors impacting Lean redesigns in primary care. RESULTS: Overall, staff engagement and performance management, sensitivity to the professional values and culture of medicine, and perceived adequacy of organizational resources were critical when introducing Lean changes. Specific drivers of change included empowerment of staff at all levels, visual display of performance metrics, and a culture of innovation and collaboration. Barriers included physician resistance to standardized work, difficulty transferring management responsibilities to non-physician staff, and time and staffing required for participating in improvement efforts. CONCLUSION: Although Lean offers a new approach to delivering care, the implementation process itself is both complex and crucial to success. Understanding early facilitators and barriers can maximize Lean's, potential to improve health care delivery.