Association of BRAFV600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers

Background: Studies have demonstrated an association of the BRAFV600E mutation and microRNA (miR) expression with aggressive clinicopathologic features in papillary thyroid cancer (PTC). Analysis of BRAFV600E mutations with miR expression data may improve perioperative decision making for patients with PTC, specifically in identifying patients harboring central lymph node metastases (CLNM). Methods: Between January 2012 and June 2013, 237 consecutive patients underwent total thyroidectomy and prophylactic central lymph node dissection (CLND) at four endocrine surgery centers. All tumors were tested for the presence of the BRAFV600E mutation and miR-21, miR-146b-3p, miR-146b-5p, miR-204, miR-221, miR-222, and miR-375 expression. Bivariate and multivariable analyses were performed to examine associations between molecular markers and aggressive clinicopathologic features of PTC. Results: Multivariable logistic regression analysis of all clinicopathologic features found miR-146b-3p and miR-146b-5p to be independent predictors of CLNM, while the presence of BRAFV600E almost reached significance. Multivariable logistic regression analysis limited to only predictors available preoperatively (molecular markers, age, sex, and tumor size) found miR-146b-3p, miR-146b-5p, miR-222, and BRAFV600E mutation to predict CLNM independently. While BRAFV600E was found to be associated with CLNM (48% mutated in node-positive cases vs. 28% mutated in node-negative cases), its positive and negative predictive values (48% and 72%, respectively) limit its clinical utility as a stand-alone marker. In the subgroup analysis focusing on only classical variant of PTC cases (CVPTC), undergoing prophylactic lymph node dissection, multivariable logistic regression analysis found only miR-146b-5p and miR-222 to be independent predictors of CLNM, while BRAFV600E was not significantly associated with CLNM. Conclusion: In the patients undergoing prophylactic CLNDs, miR-146b-3p, miR-146b-5p, and miR-222 were found to be predictive of CLNM preoperatively. However, there was significant overlap in expression of these miRs in the two outcome groups. The BRAFV600E mutation, while being a marker of CLNM when considering only preoperative variables among all histological subtypes, is likely not a useful stand-alone marker clinically because the difference between node-positive and node-negative cases was small. Furthermore, it lost significance when examining only CVPTC. Overall, our results speak to the concept and interpretation of statistical significance versus actual applicability of molecular markers, raising questions about their clinical usefulness as individual prognostic markers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140269/1/thy.2015.0378.pd

Need for weight management in Switzerland: findings from National Blood Pressure Week 2009

<p>Abstract</p> <p>Background</p> <p>The Swiss Health Survey (SHS) provides the only source of data for monitoring overweight and obesity in the general population in Switzerland. However, this survey reports body mass index (BMI) based on self-reported height and weight, and is therefore subject to measurement errors. Moreover, it is not possible to differentiate between overall and abdominal overweight. In this study, we aimed to gain a better understanding of the need for weight management in the general population of Switzerland by exploring and comparing prevalence rates of BMI and waist circumference (WC) based on physical measurements by trained observers, based on data from the 2009 National Blood Pressure Week (NBPW).</p> <p>Methods</p> <p>Sample selection was based on a one-stage cluster design. A total of 385 pharmacies representing 3,600 subjects were randomly selected from pharmacies participating in NBPW. BMI measures based on physical weight and height (NBPW) were compared with self-reported BMI measures from the SHS. BMI and WC measurements from NBPW were then used to produce population estimates of overweight and obesity.</p> <p>Results</p> <p>BMI-based overall prevalence of overweight and obesity was 43.6%, which was 4.7% higher than the value based on the respective SHS data. Overweight and obesity were more common in men (54.3%) than in women (33.5%). However, the overall prevalence of increased WC in the general population was estimated to be 64.4%, with more women (68.4%) than men (60.1%) exhibiting a WC above the threshold. The prevalence of subjects requiring weight management in the Swiss population remained high, even after adjusting WC for false positive and negative cases.</p> <p>Conclusions</p> <p>Firstly, it may be more appropriate for health promotion programs to address the wider group identified by WC, which includes subjects who need to reduce their weight, or gain no further weight. Secondly, the gender differences are reversed depending on the use of WC or BMI to identify subjects suitable for health promotion programs; more women than men are identified by WC, and more men than women using BMI. These differences should be accounted for in gender-specific health promotion programs.</p