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The mechanisms of metabolic improvements after Roux-en-Y gastric bypass (RYGB) surgery are not entirely clear. Therefore, the aim of our study was to investigate the role of obesity and RYGB on the human skeletal muscle proteome. Basal muscle biopsies were obtained from seven obese (BMI >40 kg/m2) female subjects (45.1 ± 3.6 years) pre- and 3 months post-RYGB, and euglycemic-hyperinsulinemic clamps were used to assess insulin sensitivity. Four age-matched (48.5 ± 4.7 years) lean (BMI <25 kg/m2) females served as control subjects. We performed quantitative mass spectrometry and microarray analyses on protein and RNA isolated from the muscle biopsies. Significant improvements in fasting plasma glucose (104.2 ± 7.8 vs. 86.7 ± 3.1 mg/dL) and BMI (42.1 ± 2.2 vs. 35.3 ± 1.8 kg/m2) were demonstrated in the pre- versus post-RYGB, both P < 0.05. Proteomic analysis identified 2,877 quantifiable proteins. Of these, 395 proteins were significantly altered in obesity before surgery, and 280 proteins differed significantly post-RYGB. Post-RYGB, 49 proteins were returned to normal levels after surgery. KEGG pathway analysis revealed a decreased abundance in ribosomal and oxidative phosphorylation proteins in obesity, and a normalization of ribosomal proteins post-RYGB. The transcriptomic data confirmed the normalization of the ribosomal proteins. Our results provide evidence that obesity and RYGB have a dynamic effect on the skeletal muscle proteome.

Summary For diffuse large B‐cell lymphoma ( DLBCL ) patients progressing after autologous haematopoietic cell transplantation (auto HCT ), allogeneic HCT (allo HCT ) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research ( CIBMTR ) database, we identified 503 patients who underwent allo HCT after disease progression/relapse following a prior auto HCT . The 3‐year probabilities of non‐relapse mortality, progression/relapse, progression‐free survival ( PFS ) and overall survival ( OS ) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status ( KPS ) <80, chemoresistance, auto HCT to allo HCT interval <1‐year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS <80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS , including KPS <80 (4 points), auto HCT to allo HCT interval <1‐year (2 points) and chemoresistant disease at allo HCT (5 points). This CIBMTR prognostic model classified patients into four groups: low‐risk (0 points), intermediate‐risk (2‐5 points), high‐risk (6‐9 points) or very high‐risk (11 points), predicting 3‐year PFS of 40, 32, 11 and 6%, respectively, with 3‐year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long‐term survival with allo HCT after a failed prior auto HCT .

AbstractPrecision medicine approaches disease treatment and prevention by taking patients’ individual variability in genes, environment, and lifestyle into account. Although the ideas underlying precision medicine are not new, opportunities for its more widespread use in practice have been enhanced by the development of large-scale databases, new methods for categorizing and representing patients, and computational tools for analyzing large datasets. New research methods may create uncertainty for both healthcare professionals and patients. In such situations, frameworks that address ethical, legal, and social challenges can be instrumental for facilitating trust between patients and providers, but must protect patients while not stifling progress or overburdening healthcare professionals. In this perspective, we outline several ethical, legal, and social issues related to the Precision Medicine Initiative’s proposed changes to current institutions, values, and frameworks. This piece is not an exhaustive overview, but is intended to highlight areas meriting further study and action, so that precision medicine’s goal of facilitating systematic learning and research at the point of care does not overshadow healthcare’s goal of providing care to patients.

BACKGROUNDAlthough colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown.METHODSThe current study was a population‐based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease‐specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis.RESULTSOf 258,024 patients with CRC, 37,847 (15%) were aged <50 years. Young patients were more likely to present with regional (relative risk ratio, 1.3; P<.001) or distant (relative risk ratio, 1.5; P<.001) disease. Patients with CRC with distant metastasis in the younger age group were more likely to receive surgical therapy for their primary tumor (adjusted probability: 72% vs 63%; P<.001), and radiotherapy also was more likely in younger patients with CRC (adjusted probability: 53% vs 48%; P<.001). Patients younger than the recommended screening age had better overall disease‐specific survival (hazards ratio, 0.77; P<.001), despite a larger percentage of these individuals presenting with advanced disease.CONCLUSIONSPatients with CRC diagnosed at age <50 years are more likely to present with advanced‐stage disease. However, they receive more aggressive therapy and achieve longer disease‐specific survival, despite the greater percentage of patients with advanced‐stage disease. These findings suggest the need for improved risk assessment and screening decisions for younger adults. Cancer 2016;122:929–34. © 2016 American Cancer Society.