Recent Publications by CFE Educators

INTRODUCTION

Chronic secondhand smoke (SHS) exposure increases cardiovascular events, particularly acute thrombotic events. There are little human data on acute SHS exposure. The aim of this study was to determine whether a single controlled exposure of humans to SHS increased thrombogenesis.

METHODS

After 6-8 hours fast, subjects (n = 50) were exposed to constant dose SHS (particulate level of 500 μg/m(3)) for 120 minutes in a temperature-regulated and ventilated, simulated bar environment. Blood was drawn before and immediately after SHS exposure for thromboelastography (TEG) and flow cytometry. Maximum clot strength (MA) was measured using TEG and platelet leukocyte aggregates (LPA) were measured as an index of platelet activation. Anti-CD 14 antibodies were used as leukocyte markers and anti-CD 41 antibodies as platelet markers for cytometry. Data were analyzed using students' t test for paired samples.

RESULTS

There was no effect of acute exposure to SHS on platelet activation or thrombogenesis. Also, intra group (smokers [n = 19] and nonsmokers [n = 31]) comparisons of LPA and TEG parameters did not show changes with SHS exposure.

CONCLUSIONS

While there are abundant data showing enhanced thrombogenesis and platelet activation following repeated exposure to SHS, our study suggests that a single exposure does not appear to significantly alter thrombin kinetics nor result in platelet activation. The effects of SHS on thrombogenesis might be nonlinear.

Some studies have reported that minimally invasive follicular carcinoma (MIFC) with vascular invasion is associated with compromised prognosis, leading to an ongoing debate regarding extent of surgery for MIFC. Our goal was to identify predictors of vascular invasion and determine its impact on patterns of care. Adult patients with MIFC were culled from the National Cancer Database, 2010-2011, and segregated according to the presence/absence of capsular or vascular invasion. Variables of interest were examined using Chi-square and student's t tests. Multivariate analysis was performed with logistic regression. A total of 617 patients with MIFC were identified: 54% with capsular invasion only and 46% with vascular invasion. Demographic characteristics were similarly distributed between the two groups. Tumor size was larger in patients with vascular invasion (mean = 35.7 vs. 29.2 mm capsular invasion only, p 0.001); a 2% increase in risk of vascular invasion was observed with each 1 mm increase in size. The rate of total thyroidectomy was similar for MIFCs with vascular invasion compared to capsular invasion only (72.9 vs. 75.1%, p = 0.537). The RAI administration rate was higher in patients with vascular invasion (62.1 vs. 52.6% capsular invasion only, p = 0.017). In multivariate analysis, the presence of vascular invasion was independently associated with increased likelihood of receiving RAI (OR 1.641, p = 0.007). MIFC remains aggressively treated despite current guidelines favoring a more conservative approach. Building consensus around MIFC management is important for standardization of practice patterns and improvement in quality of care.

PURPOSE

Cervical lymph node metastases are recognized as a prognostic indicator only in patients age 45 years or older with papillary thyroid cancer (PTC); patients younger than age 45 years are perceived to have low-risk disease. The current American Joint Committee on Cancer staging for PTC in patients younger than age 45 years does not include cervical lymph node metastases. Our objective was to test the hypothesis that the presence and number of cervical lymph node metastases have an adverse impact on overall survival (OS) in patients younger than age 45 years with PTC.

PATIENTS AND METHODS

Adult patients younger than age 45 years undergoing surgery for stage I PTC (no distant metastases) were identified from the National Cancer Data Base (NCDB; 1998-2006) and from SEER 1988-2006 data. Multivariable models were used to examine the association of OS with the presence of lymph node metastases and number of metastatic nodes.

RESULTS

In all, 47,902 patients in NCDB (11,740 with and 36,162 without nodal metastases) and 21,855 in the SEER database (5,188 with and 16,667 without nodal metastases) were included. After adjustment, OS was compromised for patients with nodal metastases compared with patients who did not have them (NCDB: hazard ratio (HR), 1.32; 95% CI, 1.04 to 1.67; P = .021; SEER: HR, 1.29; 95% CI, 1.08 to 1.56; P = .006). After adjustment, increasing number of metastatic lymph nodes was associated with decreasing OS up to six metastatic nodes (HR, 1.12; 95% CI, 1.01 to 1.25; P = .03), after which more positive nodes conferred no additional mortality risk (HR, 0.99; 95% CI, 0.99 to 1.05; P = .75).

CONCLUSION

Our results suggest that cervical lymph node metastases are associated with compromised survival in young patients, warranting consideration of revised American Joint Committee on Cancer staging. A change point of six or fewer metastatic lymph nodes seems to carry prognostic significance, thus advocating for rigorous preoperative screening for nodal metastases.

OBJECTIVE

Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM.

APPROACH AND RESULTS

Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27-2.50 per SD increase in ApoC-III; P0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53).

CONCLUSIONS

In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM.

OBJECTIVE

To investigate characteristics of clinical trials and results on safety and effectiveness reported in US Food and Drug Administration (FDA) documents for recently approved high risk cardiovascular devices compared with the characteristics and results reported in peer reviewed publications.

DESIGN

A search of the publicly available FDA database was performed for all cardiovascular devices that received premarket approval from 1 January 2000 to 31 December 2010. For each study listed in the premarket approval documents, a Medline search was conducted to obtain the corresponding publication.

MAIN OUTCOME MEASURES

Clinical trial characteristics, primary endpoints, and safety and efficacy results in the FDA documents and corresponding publications.

RESULTS

106 cardiovascular devices received premarket approval from 1 January 2000 to 31 December 2010. FDA premarket approval documents for these devices contained 177 studies, of which 86 (49%) had been published by 1 January 2013. These 86 publications corresponded to 60 distinct devices. The mean time from FDA approval to publication in a peer reviewed journal was 6.5 months (range -4.8-7.5 years). In 22 (26%) of the 86 compared studies the number of participants enrolled in the study differed in the FDA summary and the corresponding publications. Of 152 primary endpoints identified in the FDA documents, in the corresponding publications three (2%) were labeled as secondary, 43 (28%) were unlabeled, and 15 (10%) were not found. Among the primary results, 69 (45%) were identical, 35 (23%) were similar, 17 (11%) were substantially different, and 31 (20%) could not be compared.

CONCLUSIONS

Many clinical trials for high risk cardiovascular devices approved by the FDA remain unpublished. Even when trials are published, the study population, primary endpoints, and results can differ substantially from data submitted to the FDA.

OBJECTIVES

To analyze the postoperative complications and mortality for oral cavity cancers, their time course, and to identify modifiable risk factors associated with their occurrence.

STUDY DESIGN

Retrospective cohort study.

METHODS

Patients undergoing surgery for oral cavity cancer were identified in the American College of Surgeons National Surgical Quality Improvement Program Participant Use Data File (2005-2010). Overall and disease-specific complication and mortality data were analyzed using chi-square and multivariate regression analysis.

RESULTS

There were 408 cases identified. The overall 30-day complication and mortality rates were 20.3% and 1.0%, respectively. The most common adverse events were reoperation (9.6%), infectious (6.6%), and respiratory (5.1%) complications. Twenty patients (4.9%) experienced postdischarge complications. Fifty-two percent of postdischarge wound dehiscences and 67% of postdischarge surgical-site infections occurred by postdischarge day 7, and 91% of all postdischarge complications occurred by postdischarge day 14. Smoking was independently associated with respiratory (odds ratio [OR] 3.59, P = .008) and surgical site complications (OR 5.13, P =.004). Neck dissection was independently associated with respiratory (OR 6.17, P = .001), surgical site (OR 6.30, P = .003), and infectious (OR 3.83, P = .003) complications.

CONCLUSION

Current smokers and those undergoing neck dissection are at high risk of postoperative complications after oral cavity cancer surgery. Less than 5% of patients experienced postdischarge complications, nearly all of which occurred by postdischarge day 14. Most early postdischarge complications occurred at the surgical site. In order to mitigate postdischarge complications and their sequelae, early clinical follow-up should be sought for high-risk patients.

LEVEL OF EVIDENCE

4.

Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.