A real-world study of cardiac events in > 3700 patients with HER2-positive early breast cancer treated with trastuzumab: final analysis of the OHERA study.

PURPOSE: Cardiac dysfunction risk associated with intravenous trastuzumab (H IV) treatment may differ in real-world practice versus randomized trials. We investigated cardiac events in patients with HER2-positive early breast cancer (EBC) treated with H IV as adjuvant therapy in routine practice. METHODS: The observational study of cardiac events in patients with HER2-positive EBC treated with Herceptin (OHERA; NCT01152606) enrolled patients with stage I-IIIb disease eligible for H IV in the adjuvant setting per the European Summary of Product Characteristics (SmPC). Primary outcomes were symptomatic congestive heart failure incidence (CHF; New York Heart Association class II-IV) and cardiac death. Patient visits/assessments were per local practice. RESULTS: 3733 Patients received ≥ 1 H IV dose per local practice; 88.9% received H IV for > 300 days (median follow-up: ~ 5 years). Prior to disease recurrence (if any), symptomatic CHF occurred in 106 patients (2.8%); 6 (0.2%) cardiac deaths occurred (5 in patients with cardiac disease history). Median time to symptomatic CHF onset was 5.7 months (95% CI 5.3-6.5); 77/106 (72.6%) patients with symptomatic CHF achieved resolution. CHF incidence was higher in patients ≥ 65 years, and those with pre-existing cardiac conditions, hypertension, or left ventricular ejection fraction ≤ 55% at baseline. CONCLUSIONS: OHERA is the largest prospective observational study to investigate the cardiac safety of H IV as adjuvant EBC therapy in a real-world setting. Symptomatic CHF and cardiac event incidences were consistent with randomized trials in this setting and baseline risk factors identified in the H IV European SmPC.

[Preoperative factors of misdiagnosis of renal angiomyolipoma]. / Facteurs associés à l'échec du diagnostic préopératoire des angiomyolipomes rénaux.

OBJECTIVES: To explain the high incidence of misdiagnosis of angiomyolipoma (AML) prior to surgery. MATERIALS AND METHODS: Between 1989 and 2007, 2,657 patients were operated for a renal tumor at Dupuytren hospital in Limoges and at Cochin hospital in Paris. In 85 cases (3.2%), tumors were AMLs on pathology. The group of patients in which the diagnosis was done preoperatively was compared to the one in which the diagnosis was missed. RESULTS: Mean age of patients was 57-years-old and the sex-ratio was five women for one man. The mean size of AMLs was 5.4 cm. The patients were symptomatic in 46% of cases (39/85). The diagnosis of AML was ignored preoperatively in 62 patients (73%). In multivariate analysis, the small size of the AML, low proportion of fat and male sex were significantly associated with misdiagnosis of AML (p<0.001, p<0.018 and p<0.008, respectively). CONCLUSIONS: The incidence of misdiagnosis of AML preoperatively is high. The diagnosis seems particularly difficult when the tumor is small or contains a small proportion of fat. In addition, this study highlights that the diagnosis of AML is frequently ignored in men. The increased resolution of CTscan and the use of preoperative biopsies for tumors less than 4 cm could be helpful to decrease the incidence of useless surgery of AMLs.

Nandrolone decanoate pre-treatment attenuates unweighting-induced functional changes in rat soleus muscle.

The effect of nandrolone decanoate pre-treatment (15 mg kg(-1) week(-1), for 6 weeks) was tested on the changes in mass and contractile properties of soleus muscle associated with 3 weeks of hindlimb suspension. Male rats were assigned to four groups (eight animals/group): control, nandrolone decanoate hindlimb-loaded, hindlimb-unweighted and nandrolone decanoate hindlimb-unweighted. Compared with age-matched control values, suspension induced a reduction in relative muscle mass and a shift in tension characteristics from slow-towards fast-twitch type. Nandrolone decanoate pre-treatment of suspended animals (nandrolone decanoate hindlimb-unweighted vs. nandrolone decanoate hindlimb-loaded) partially spared the relative soleus mass. Furthermore, (1) the relative twitch tension (nandrolone decanoate hindlimb-loaded: 5.4 +/- 0.7%; nandrolone decanoate hindlimb-unweighted: 5.1 +/- 0.5%), (2) the time to peak tension (nandrolone decanoate hindlimb-loaded: 152 +/- 9 ms; nandrolone decanoate hindlimb-unweighted: 167 +/- 15 ms), (3) the time constant of relaxation (nandrolone decanoate hindlimb-loaded: 274 +/- 12 ms; nandrolone decanoate hindlimb-unweighted: 245 +/- 20 ms), (4) the relative K+ contracture tension (nandrolone decanoate hindlimb-loaded: 81.7 +/- 3.8%; nandrolone decanoate hindlimb-unweighted: 86.9 +/- 4.2%) and (5) the relative caffeine contracture tension (0.5 mM) (nandrolone decanoate hindlimb-loaded: 5.2 +/- 0.8%; nandrolone decanoate hindlimb-unweighted: 5.9 +/- 1.1%) were not significantly modified. The present results demonstrate that exogenously provided nandrolone decanoate pre-treatment attenuates functional changes occurring in soleus muscle subject to unweighting.