Atherosclerosis is mediated by local and systematic inflammation. The multiligand receptor for advanced glycation end products (RAGE) has been studied in animals and humans and is an important mediator of inflammation and atherosclerosis. This review focuses on S100/calgranulin proteins (S100A8, S100A9, and S100A12) and their receptor RAGE in mediating vascular inflammation. Mice lack the gene for S100A12, which in humans is located on chromosome 3 between S100A8 and S100A9. Transgenic mice with smooth muscle cell-targeted expression of S100A12 demonstrate increased coronary and aortic calcification, as well as increased plaque vulnerability. Serum S100A12 has recently been shown to predict future cardiovascular events in a longitudinal population study, underscoring a role for S100A12 as a potential biomarker for coronary artery disease. Genetic ablation of S100A9 or RAGE in atherosclerosis-susceptible apolipoprotein E null mice results in reduced atherosclerosis. Importantly, S100A12 and the RAGE axis can be modified pharmacologically. For example, soluble RAGE reduces murine atherosclerosis and vascular inflammation. Additionally, a class of compounds currently in phase III clinical trials for multiple sclerosis and rheumatologic conditions, the quinoline-3-carboxamides, reduce atherosclerotic plaque burden and complexity in transgenic S100A12 apolipoprotein E null mice, but have not been tested with regards to human atherosclerosis. The RAGE axis is an important mediator for inflammation-induced atherosclerosis, and S100A12 has emerged as biomarker for human atherosclerosis. Decreasing inflammation by inhibiting S100/calgranulin-mediated activation of RAGE attenuates murine atherosclerosis, and future studies in patients with coronary artery disease are warranted to confirm S100/RAGE as therapeutic target for atherosclerosis.

PURPOSE

To estimate the effects of a tablet-based, breast cancer risk education intervention for use in primary care settings (BreastCARE) on patients' breast cancer knowledge, risk perception and concern.

METHODS

From June 2011-August 2012, we enrolled women from two clinics, aged 40-74 years with no personal breast cancer history, and randomized them to the BreastCARE intervention group or to the control group. All patients completed a baseline telephone survey and risk assessment (via telephone for controls, via tablet computer in clinic waiting room prior to visit for intervention). All women were categorized as high or average risk based on the Referral Screening Tool, the Gail model or the Breast Cancer Surveillance Consortium model. Intervention patients and their physicians received an individualized risk report to discuss during the visit. All women completed a follow-up telephone survey 1-2 weeks after risk assessment. Post-test comparisons estimated differences at follow-up in breast cancer knowledge, risk perception and concern.

RESULTS

580 intervention and 655 control women completed follow-up interviews. Mean age was 56 years (SD = 9). At follow-up, 73% of controls and 71% of intervention women correctly perceived their breast cancer risk and 22% of controls and 24% of intervention women were very concerned about breast cancer. Intervention patients had greater knowledge (≥75% correct answers) of breast cancer risk factors at follow-up (24% vs. 16%; p = 0.002). In multivariable analysis, there were no differences in correct risk perception or concern, but intervention patients had greater knowledge ([OR] = 1.62; 95% [CI] = 1.19-2.23).

CONCLUSIONS

A simple, practical intervention involving physicians at the point of care can improve knowledge of breast cancer without increasing concern.

TRIAL REGISTRATION

ClinicalTrials.gov identifier NCT01830933.

BACKGROUND & AIMS

As many as 50% of large sessile serrated adenomas/polyps (SSPs) are removed incompletely, which is significant because SSPs have been implicated in the development of interval cancers. It is unclear if endoscopic mucosal resection (EMR) is an optimal method for removal of SSPs. We assessed the efficacy and safety of removal of SSPs 10 mm and larger using a standardized inject-and-cut EMR technique.

METHODS

We performed a retrospective analysis of colonoscopy data, collected over 7 years (2007-2013) at 2 centers, from 199 patients with proximal colon SSPs 10 mm and larger (251 polyps) removed by EMR by 4 endoscopists. The primary outcome measure was local recurrence. The secondary outcome measure was safety.

RESULTS

At the index colonoscopy, patients had a median of 1 serrated lesion (range, 1-12) and 1 nonserrated neoplastic lesion (range, 0-15). The mean SSP size was 15.9 ± 5.3 mm; most were superficially elevated (84.5%) and located in the ascending colon (51%), and 3 SSPs (1.2%) had dysplasia. Surveillance colonoscopies were performed on 138 patients (69.3%) over a mean follow-up period of 25.5 ± 17.4 months. Of these patients, 5 had local recurrences (3.6%; 95% confidence interval, 0.5%-6.7%), detected after 17.8 ± 15.4 months, with a median size of 4 mm. No patients developed postprocedural bleeding, perforation, or advanced colon cancer, or had a death related to the index colorectal lesion during the study period.

CONCLUSIONS

Inject-and-cut EMR is a safe and effective technique for the resection of SSPs. Less than 5% of patients have a local recurrence, which is usually small and can be treated endoscopically.