ABSTRACT
Extensive metabolic heterogeneity in breast cancers has limited the deployment of metabolic therapies. To enable patient stratification, we studied the metabolic landscape in breast cancers (â¼3000 patients combined) and identified three subtypes with increasing degrees of metabolic deregulation. Subtype M1 was found to be dependent on bile-acid biosynthesis, whereas M2 showed reliance on methionine pathway, and M3 engaged fatty-acid, nucleotide, and glucose metabolism. The extent of metabolic alterations correlated strongly with tumor aggressiveness and patient outcome. This pattern was reproducible in independent datasets and using in vivo tumor metabolite data. Using machine-learning, we identified robust and generalizable signatures of metabolic subtypes in tumors and cell lines. Experimental inhibition of metabolic pathways in cell lines representing metabolic subtypes revealed subtype-specific sensitivity, therapeutically relevant drugs, and promising combination therapies. Taken together, metabolic stratification of breast cancers can thus aid in predicting patient outcome and designing precision therapies.
ABSTRACT
OBJECTIVE: To test the hypothesis: Time to ambulation (walking) after hip fracture surgery impacts the frequency of postoperative complications and length of hospital stay. METHODS: A retrospective observational study of a cohort of all patients admitted to a university teaching hospital with a principal International Classification of Diseases-9 diagnosis of a hip fracture during 3 calendar years. RESULTS: A total of 131 participants were identified (68% were aged 65 years or older). Overall, the mean time to writing an order to ambulate a patient after a hip fracture surgery was 2 +/- 1.5 days. Time to ambulation after hip fracture surgery was significantly less in patients cared for on orthopedic surgery service compared to general surgery service (1.8 +/- 1 vs 2.5 +/- 2, p <.05) or general internal medicine service (2.5 +/- 1.5, p <.05). It did not relate, however, to patient's age, sex, or race, or to patient's functional status prior to admission, fracture site (femoral neck, intertrochanteric, or subtrochanteric), whether a femoral neck fracture is displaced or not, type of anesthesia (spinal/epidural vs general), type of surgery (open reduction and internal fixation vs hemiarthroplasty), degree of preoperative risk, number of medical conditions, or to obtaining physical therapy and/or medical consultation. Time to ambulation after surgery was an independent predictor for the development of pneumonia (1.5 OR [odds ratio]/day, p <.001), new onset delirium (1.7 OR/day, p <.001), and to prolonged length of hospital stay (B [slope coefficient] = 1.36, p <.0001) but not to the development of pressure ulcers, deep venous thrombosis, or urinary tract infection. CONCLUSIONS: Delayed ambulation after hip fracture surgery is related to the development of new onset delirium and pneumonia postoperatively as well as to increased length of hospital stay. Early ambulation after hip fracture surgery should be encouraged.
