Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Elderly Adults With Isolated Hip Fractures- Orthogeriatric Care Versus Standard Care: A Practice Management Guideline From the Eastern Association for the Surgery of Trauma

BACKGROUND: Elderly patients commonly suffer isolated hip fractures, causing significant morbidity and mortality. The use of orthogeriatrics (OG) management services, in which geriatric specialists primarily manage or co-manage patients after admission, may improve outcomes. We sought to provide recommendations regarding the role of OG services. METHODS: Using GRADE methodology with meta-analyses, the Practice Management Guidelines Committee of the Eastern Association for the Surgery of Trauma conducted a systematic review of the literature from January 1, 1900 to August 31, 2017. A single PICO question was generated with multiple outcomes: Should geriatric trauma patients aged 65+ with isolated hip fracture receive routine OG management, compared to no routine OG management, to decrease mortality, improve discharge disposition, improve functional outcomes, decrease in-hospital medical complications, and decrease hospital length of stay. RESULTS: Forty-five manuscripts were evaluated. Six randomized controlled trials and seven retrospective case-control studies (RCCS) met criteria for quantitative analysis. For critical outcomes, RCCS demonstrated a 30-day mortality benefit with OG (OR 0.78[0.67, 0.90]), but this was not demonstrated prospectively or at one year. Functional outcomes were superior with OG, specifically improved score on the Short Physical Performance Battery at four months (MD 0.78 [0.28, 1.29]), and improved score on the Mini Mental Status Exam with OG at 12 months (MD 1.57 [0.40, 2.73]). Execution of activities of daily living was improved with OG as measured by two separate tests at four and twelve months. There was no difference in discharge disposition. Among important outcomes, the OG group had fewer hospital-acquired pressure ulcers (OR 0.30 [0.15, 0.60]). There was no difference in other complications or length of stay. Overall quality of evidence was low. CONCLUSIONS: In geriatric patients with isolated hip fracture, we conditionally recommend an OG care model to improve patient outcomes. LEVEL OF EVIDENCE: Level III evidenceSystematic Review/Meta-Analysis