Comparative performance of multiview stereoscopic and mammographic display modalities for breast lesion detection.

PURPOSE: Mammography is known to be one of the most difficult radiographic exams to interpret. Mammography has important limitations, including the superposition of normal tissue that can obscure a mass, chance alignment of normal tissue to mimic a true lesion and the inability to derive volumetric information. It has been shown that stereomammography can overcome these deficiencies by showing that layers of normal tissue lay at different depths. If standard stereomammography (i.e., a single stereoscopic pair consisting of two projection images) can significantly improve lesion detection, how will multiview stereoscopy (MVS), where many projection images are used, compare to mammography? The aim of this study was to assess the relative performance of MVS compared to mammography for breast mass detection. METHODS: The MVS image sets consisted of the 25 raw projection images acquired over an arc of approximately 45 degrees using a Siemens prototype breast tomosynthesis system. The mammograms were acquired using a commercial Siemens FFDM system. The raw data were taken from both of these systems for 27 cases and realistic simulated mass lesions were added to duplicates of the 27 images at the same local contrast. The images with lesions (27 mammography and 27 MVS) and the images without lesions (27 mammography and 27 MVS) were then postprocessed to provide comparable and representative image appearance across the two modalities. All 108 image sets were shown to five full-time breast imaging radiologists in random order on a state-of-the-art stereoscopic display. The observers were asked to give a confidence rating for each image (0 for lesion definitely not present, 100 for lesion definitely present). The ratings were then compiled and processed using ROC and variance analysis. RESULTS: The mean AUC for the five observers was 0.614 +/- 0.055 for mammography and 0.778 +/- 0.052 for multiview stereoscopy. The difference of 0.164 +/- 0.065 was statistically significant with a p-value of 0.0148. CONCLUSIONS: The differences in the AUCs and the p-value suggest that multiview stereoscopy has a statistically significant advantage over mammography in the detection of simulated breast masses. This highlights the dominance of anatomical noise compared to quantum noise for breast mass detection. It also shows that significant lesion detection can be achieved with MVS without any of the artifacts associated with tomosynthesis.

Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated skin and skin-structure infection (cSSSI). Increasing antimicrobial resistance in cSSSI has led to a need for new safe and effective therapies. Ceftaroline was evaluated as treatment for cSSSI in 2 identical phase 3 clinical trials, the pooled analysis of which is presented here. The primary objective of each trial was to determine the noninferiority of the clinical cure rate achieved with ceftaroline monotherapy, compared with that achieved with vancomycin plus aztreonam combination therapy, in the clinically evaluable (CE) and modified intent-to-treat (MITT) patient populations. METHODS: Adult patients with cSSSI requiring intravenous therapy received ceftaroline (600 mg every 12 h) or vancomycin plus aztreonam (1 g each every 12 h) for 5-14 days. RESULTS: Of 1378 patients enrolled in both trials, 693 received ceftaroline and 685 received vancomycin plus aztreonam. Baseline characteristics of the treatment groups were comparable. Clinical cure rates were similar for ceftaroline and vancomycin plus aztreonam in the CE (91.6% vs 92.7%) and MITT (85.9% vs 85.5%) populations, respectively, as well as in patients infected with MRSA (93.4% vs 94.3%). The rates of adverse events, discontinuations because of an adverse event, serious adverse events, and death also were similar between treatment groups. CONCLUSIONS: Ceftaroline achieved high clinical cure rates, was efficacious against cSSSI caused by MRSA and other common cSSSI pathogens, and was well tolerated, with a safety profile consistent with the cephalosporin class. Ceftaroline has the potential to provide a monotherapy alternative for the treatment of cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.

G protein signaling and vein graft intimal hyperplasia: reduction of intimal hyperplasia in vein grafts by a Gbetagamma inhibitor suggests a major role of G protein signaling in lesion development.

Vein grafting results in the development of intimal hyperplasia with accompanying changes in guanine nucleotide-binding (G) protein expression and function. Several serum mitogens that act through G protein-coupled receptors, such as lysophosphatidic acid, stimulate proliferative pathways that are dependent on the G protein betagamma subunit (Gbetagamma)-mediated activation of p21ras. This study examines the role of Gbetagamma signaling in intimal hyperplasia by targeting a gene encoding a specific Gbetagamma inhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the beta-adrenergic receptor kinase (betaARK(CT)), contains a Gbetagamma-binding domain. Vein graft intimal hyperplasia was significantly reduced by 37% (P<0.01), and physiological studies demonstrated that the normal alterations in G protein coupling phenotypically seen in this model were blocked by betaARK(CT) treatment. Thus, it appears that Gbetagamma-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of Gbetagamma signaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.