Expanding the Etiology of Oculo-Auriculo-Vertebral Spectrum: A Novel Interstitial Microdeletion at 1p36.

The etiology of oculo-auriculo-vertebral spectrum (OAVS) is not well established. About half of patients show a positive family history. The etiology of familiar cases is unclear but appears genetically heterogeneous. This motivated us to report a case of OAVS with microtia, ptosis, facial microsomy, and fusion of vertebral bodies associated with a novel genetic etiology, including a deletion at 1p36.12-13. This case report expands on the genetic etiology of OAVS. Furthermore, it also expands the clinical manifestations of patients with interstitial deletions of the de 1p36.12-13 region.

Funding models in palliative care: Lessons from international experience.

BACKGROUND: Funding models influence provision and development of palliative care services. As palliative care integrates into mainstream health care provision, opportunities to develop funding mechanisms arise. However, little has been reported on what funding models exist or how we can learn from them. AIM: To assess national models and methods for financing and reimbursing palliative care. DESIGN: Initial literature scoping yielded limited evidence on the subject as national policy documents are difficult to identify, access and interpret. We undertook expert consultations to appraise national models of palliative care financing in England, Germany, Hungary, Republic of Ireland, New Zealand, The Netherlands, Norway, Poland, Spain, Sweden, Switzerland, the United States and Wales. These represent different levels of service development and a variety of funding mechanisms. RESULTS: Funding mechanisms reflect country-specific context and local variations in care provision. Patterns emerging include the following: Provider payment is rarely linked to population need and often perpetuates existing inequitable patterns in service provision. Funding is frequently characterised as a mixed system of charitable, public and private payers. The basis on which providers are paid for services rarely reflects individual care input or patient needs. CONCLUSION: Funding mechanisms need to be well understood and used with caution to ensure best practice and minimise perverse incentives. Before we can conduct cross-national comparisons of costs and impact of palliative care, we need to understand the funding and policy context for palliative care in each country of interest.

Biological characterization of ETP-46321 a selective and efficacious inhibitor of phosphoinositide-3-kinases.

Inhibitors of PI3K signaling are of great therapeutic interest in oncology. The phosphoinositide-3-kinase signaling pathway is activated in a variety of solid and non-solid tumors. We have identified an imidazopyrazine derivative, ETP-46321, as a potent inhibitor of PI3Kα [Formula: see text]. The compound was 6 times less potent towards PI3Kδ and more than 200 and 60 times less potent at inhibiting PI3Kß and PI3Kγ and did not significantly inhibit the related phosphoinositide-3-kinase-related protein kinase family kinases mTOR or DNA PK (IC(50)'s > 5 µM), or an additional 287 protein kinases that were screened. ETP-46321 inhibited PI3K signaling in treated tumor cell lines, induced cell cycle arrest and inhibited VEGF-dependent sprouting of HUVEC cells. The compound was anti-proliferative and synergized with both cytotoxic and targeted therapeutics. The compound induced a reduction in the phosphorylation of Akt in U87 MG xenografts after a single treatment. The growth of colon and lung cancinoma HT-29 and A549 xenografts was delayed by once a day treatment with ETP-46321. The compound synergized with Doxotaxel in a model of ovarian cancer.

Management of oligometastatic non-small cell lung cancer patients: Current controversies and future directions.

Oligometastatic non-small cell lung cancer (NSCLC) describes an intermediate stage of NSCLC between localized and widely-disseminated disease. This stage of NSCLC is characterized by a limited number of metastases and a more indolent tumor biology. Currently, the management of oligometastatic NSCLC involves radical treatment (radiotherapy or surgery) that targets the metastatic lesions and the primary tumor to achieve disease control. This approach offers the potential to achieve prolonged survival in patients who, in the past, would have only received palliative measures. The optimal therapeutic strategies for the different scenarios of oligometastatic disease (intracranial vs extracranial disease, synchronous vs metachronous) remain undefined. Given the lack of head-to-head studies comparing radiotherapy to surgery in these patients, the decision to apply surgery or radiotherapy (with or without systemic treatment) must be based on prognostic factors that allow us to classify patients. This classification will allow us to select the most appropriate therapeutic strategy on an individualized basis. In the future, the molecular or microRNA profiles will likely improve the treatment selection process. The objective of the present article is to review the most relevant scientific evidence on the management of patients with oligometastatic NSCLC, focusing on the role of radiotherapy and surgery. We also discuss areas of controversy and future directions.