Background: Estimating distant recurrence (DR) risk among women with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2 (HER2)–negative early breast cancer helps decisions on using adjuvant chemotherapy. The 21-gene Oncotype DX recurrence score (RS) is widely used for this. EndoPredict (EPclin) is an alternative test combining prognostic information from an eight-gene signature (EP score) with tumor size and nodal status. We compared the prognostic information provided by RS and EPclin for 10-year DR risk.Methods: We used likelihood ratio χ² and Kaplan-Meier survival analyses to compare prognostic information provided by EP, EPclin, RS, and the clinical treatment score (CTS) of clinicopathologic parameters in 928 patients with ER+ disease treated with five years’ anastrozole or tamoxifen. Comparisons were made for early (0-5 years) and late (5-10 years) DR according to nodal status. All statistical tests were two-sided.Results: In the overall population, EP and EPclin provided substantially more prognostic information than RS (LRχ2: EP = 49.3; LRχ2: EPclin = 139.3; LRχ2: RS = 29.1), with greater differences in late DR and in node-positive patients. EP and EPclin remained statistically significantly prognostic when adjusted for RS (ΔLRχ2: EP+RS vs RS = 20.2; ΔLRχ2: EPclin+RS vs RS = 113.8). Using predefined cut-offs, EPclin and RS identified 58.8% and 61.7% patients as low risk, with hazard ratios for non-low vs low risk of 5.99 (95% confidence interval [CI] = 3.94 to 9.11) and 2.73 (95% CI = 1.91 to 3.89), respectively.Conclusions: EP and EPclin were highly prognostic for DR in endocrine-treated patients with ER+, HER2-negative disease. EPclin provided more prognostic information than RS. This was partly but not entirely because of EPclin integrating molecular data with nodal status and tumor size.

OBJECTIVETo estimate the impact of diabetes on mortality in patients after first major lower extremity amputation (LEA).RESEARCH DESIGN AND METHODSUsing claims data of a nationwide statutory health insurance, we assessed all deaths in a cohort of all 444 patients with a first major LEA since 2005 (71.8% male; mean age 69.1 years; 58.3% diabetic; 43% with amputation above the knee) up to 2009. Using Cox regression, we estimated the time-dependent hazard ratios to compare patients with and without diabetes.RESULTSThe cumulative 5-year mortality was 68% in diabetic and 59% in nondiabetic individuals. In the first course, mortality was lower in diabetic compared with nondiabetic patients. Later, the diabetes risk increased yielding crossed survival curves after 2 to 3 years (time dependency of diabetes; P = 0.003). Age- and sex-adjusted hazard ratios for diabetes were as follows: 0–30 days: 0.50 [95% CI 0.31–0.84]; 31–60 days: 0.60 [0.25–1.41]; 61 days to 6 months: 0.75 [0.38–1.48]; >6–12 months: 1.27 [0.63–2.53]; >12–24 months: 1.65 [0.88–3.08]; >24–36 months: 2.02 [0.80–5.09]; and >36–60 months: 1.91 [0.70–5.21]. The pattern was similar in both sexes. In the full model, significant risk factors for mortality were age (1.05; 1.03–1.06), amputation above the knee (1.50; 1.16–1.94), and quartile category 3 or 4 of the number of prescribed medications (1.64; 1.12–2.40 and 1.76; 1.20–2.59). Further adjustment for comorbidity did not alter the results.CONCLUSIONSIn this population-based study, we found a time-dependent mortality risk of diabetes following first major LEA, which may be in part a result of a healthier lifestyle in diabetic patients or the access to specific treatment structures in diabetic individuals.

Metabolome analyses from recent-onset T2D and T1D patients enables identification of defined diabetes type-specific differences and detection of biomarkers of insulin sensitivity. These analyses may help to identify novel clinical subphenotypes diabetes.