Dedicated Cone-Beam Breast CT: Reproducibility of Volumetric Glandular Fraction with Advanced Image Reconstruction Methods.

Dedicated cone-beam breast computed tomography (CBBCT) is an emerging modality and provides fully three-dimensional (3D) images of the uncompressed breast at an isotropic voxel resolution. In an effort to translate this modality to breast cancer screening, advanced image reconstruction methods are being pursued. Since radiographic breast density is an established risk factor for breast cancer and CBBCT provides volumetric data, this study investigates the reproducibility of the volumetric glandular fraction (VGF), defined as the proportion of fibroglandular tissue volume relative to the total breast volume excluding the skin. Four image reconstruction methods were investigated: the analytical Feldkamp-Davis-Kress (FDK), a compressed sensing-based fast, regularized, iterative statistical technique (FRIST), a fully supervised deep learning approach using a multi-scale residual dense network (MS-RDN), and a self-supervised approach based on Noise-to-Noise (N2N) learning. Projection datasets from 106 women who participated in a prior clinical trial were reconstructed using each of these algorithms at a fixed isotropic voxel size of (0.273 mm3). Each reconstructed breast volume was segmented into skin, adipose, and fibroglandular tissues, and the VGF was computed. The VGF did not differ among the four reconstruction methods (p = 0.167), and none of the three advanced image reconstruction algorithms differed from the standard FDK reconstruction (p > 0.862). Advanced reconstruction algorithms developed for low-dose CBBCT reproduce the VGF to provide quantitative breast density, which can be used for risk estimation.

Randomized, double-blind, placebo-controlled trial of sulindac in individuals at risk for melanoma: evaluation of potential chemopreventive activity.

BACKGROUND: Reduced melanoma risk has been reported with regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the ability of NSAIDs to reach melanocytes in vivo and modulate key biomarkers in preneoplastic lesions such as atypical nevi has not been evaluated. METHODS: This randomized, double-blind, placebo-controlled trial of sulindac was conducted in individuals with atypical nevi (AN) to determine bioavailability of sulindac and metabolites in nevi and effect on apoptosis and vascular endothelial growth factor A (VEGFA) expression in AN. Fifty subjects with AN ≥ 4 mm in size and 1 benign nevus (BN) were randomized to sulindac (150 mg twice a day) or placebo for 8 weeks. Two AN were randomized for baseline excision, and 2 AN and BN were excised after intervention. RESULTS: Postintervention sulindac, sulindac sulfone, and sulindac sulfide concentrations were 0.31 ± 0.36, 1.56 ± 1.35, and 2.25 ± 2.24 µg/mL in plasma, and 0.51 ± 1.05, 1.38 ± 2.86, and 0.12 ± 0.12 µg/g in BN, respectively. Sulindac intervention did not significantly change VEGFA expression but did increase expression of the apoptotic marker cleaved caspase-3 in AN (increase of 3 ± 33 in sulindac vs decrease of 25 ± 45 in the placebo arm, P = .0056), although significance was attenuated (P = .1103) after adjusting for baseline expression. CONCLUSIONS: Eight weeks of sulindac intervention resulted in high concentrations of sulindac sulfone, a proapoptotic metabolite, in BN but did not effectively modulate VEGFA and cleaved caspase-3 expression. Study limitations included limited exposure time to sulindac and the need to optimize a panel of biomarkers for NSAID intervention studies.

The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults.

Folklore has suggested that consuming grapefruit may promote weight control. Sparse data exist to support this hypothesis, although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids. The aim of this randomized controlled trial was to prospectively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults (N = 74). Following a 3-week washout diet low in bioactive-rich fruits and vegetables, participants were randomized to either the control diet (n = 32) or daily grapefruit (n = 42) in the amount of one half of a fresh Rio-Red grapefruit with each meal (3× daily) for 6 weeks. No differences between group in weight, blood pressure, or lipids were demonstrated. Grapefruit consumption was associated with modest weight loss (-0.61 ± 2.23 kg, P = .097), a significant reduction in waist circumference (-2.45 ± 0.60 cm, P = .0002), and a significant reduction in systolic blood pressure (-3.21 ± 10.13 mm Hg, P = .03) compared with baseline values. Improvements were observed in circulating lipids of those consuming grapefruit, with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL (P = .002) and -18.7 mg/dL (P < .001), respectively, compared with baseline values. This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight, lipids, or blood pressure as compared with the control condition. However, the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention.