Intermuscular Adipose Tissue Is Muscle Specific and Associated with Poor Functional Performance

Purpose. People with obesity, diabetes, and peripheral neuropathy have high levels of intermuscular adipose tissue (IMAT) volume which has been inversely related to physical function. We determined if IMAT is muscle specific, if calf IMAT is different between a healthy obese group (HO), a group with diabetes mellitus (D), and a group with diabetes mellitus and peripheral neuropathy (DN), and if IMAT volume or the ratio of IMAT/muscle volume is related to physical function in these groups. Methods. 10 healthy obese people, 11 with type 2 diabetes, 24 with diabetes and peripheral neuropathy, had assessments of muscle morphology, physical function and muscle performance. Results. The gastrocnemius muscle had a higher ratio of IMAT/muscle volume than any other muscle or compartment. There were no differences between groups in calf muscle or IMAT volumes. Calf IMAT was inversely related to physical performance on the 6-minute walk test (r = −0.47) and physical performance test (r = −0.36). IMAT/muscle volume was inversely related to physical performance (PPT, r = −0.44; 6 MW r = −0.48; stair power, r = −0.30). Conclusions. IMAT accumulation varies in calf muscles, is highest in the gastrocnemius muscle, and is associated with poor physical performance

Selumetinib Plus Adjuvant Radioactive Iodine in Patients with High-Risk Differentiated Thyroid Cancer : A Phase III, Randomized, Placebo-Controlled Trial (ASTRA)

PURPOSESelumetinib can increase radioactive iodine (RAI) avidity in RAI-refractory tumors. We investigated whether selumetinib plus adjuvant RAI improves complete remission (CR) rates in patients with differentiated thyroid cancer (DTC) at high risk of primary treatment failure versus RAI alone.METHODSASTRA (ClinicalTrials.gov identifier: NCT01843062) is an international, phase III, randomized, placebo-controlled, double-blind trial. Patients with DTC at high risk of primary treatment failure (primary tumor > 4 cm; gross extrathyroidal extension outside the thyroid gland [T4 disease]; or N1a/N1b disease with ≥ 1 metastatic lymph node(s) ≥ 1 cm or ≥ 5 lymph nodes [any size]) were randomly assigned 2:1 to selumetinib 75 mg orally twice daily or placebo for approximately 5 weeks (no stratification). On treatment days 29-31, recombinant human thyroid-stimulating hormone (0.9 mg)-stimulated RAI (131I; 100 mCi/3.7 GBq) was administered, followed by 5 days of selumetinib/placebo. The primary end point (CR rate 18 months after RAI) was assessed in the intention-to-treat population.RESULTSFour hundred patients were enrolled (August 27, 2013-March 23, 2016) and 233 randomly assigned (selumetinib, n = 155 [67%]; placebo, n = 78 [33%]). No statistically significant difference in CR rate 18 months after RAI was observed (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI, 0.61 to 1.87]; P =.8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo. The most common adverse event with selumetinib was dermatitis acneiform (n = 11 [7%]). No treatment-related deaths were reported.CONCLUSIONPostoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients. Future strategies should focus on tumor genotype-tailored drug selection and maintaining drug dosing to optimize RAI efficacy