Citations

Abstract Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10−5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420–4. ©2016 AACR.

Hematopoietic cell transplantation (HCT) is an important and complex treatment modality for a variety of hematologic malignancies and some solid tumors. Although outcomes of patients who have undergone HCT and require care in intensive care units (ICUs) have improved over time, mortality rates remain high and there are significant associated costs. Lack of a team-based approach to care, especially during critical illness, is detrimental to patient autonomy and satisfaction, and to team morale, ultimately leading to poor quality of care. In this manuscript, we describe the case of a patient who had undergone HCT and was in the ICU setting, where inconsistent team interaction among the various stakeholders delivering care resulted in a lack of shared goals and poor outcomes. Team cognition is cognitive processing at the team level through interactions among team members and is reflected in dynamic communication and coordination behaviors. Although the patient received multidisciplinary care as needed in a medically complicated case, a lack of team cognition and, particularly, inconsistent communication among the dynamic teams caring for the patient, led to mixed messages being delivered with high-cost implications for the health-care system and the family. This article highlights concepts and recommendations that begin a necessary in-depth assessment of implications for clinical care and initiate a research agenda that examines the effects of team cognition on HCT teams, and, more generally, critical care of the patient with cancer.

PurposeInfarct mass as assessed by myocardial‐delayed enhancement imaging on cardiac magnetic resonance (CMR) and myocardial blood flow as assessed by real time myocardial perfusion echocardiography (RT‐MPE) have been shown to predict adverse events following ST elevation myocardial infarction (STEMI). There has been no published comparison of quantitative assessment using these modalities as predictors of clinical outcomes to date. We compared RT‐MPE with CMR for prediction of cardiac events in reperfused STEMI patients.Materials and MethodsConsecutive STEMI patients with early reperfusion were studied. RT‐MPE and CMR were performed. Perfusion score indices (PSIRT‐MPE and PSICMR) were calculated [sum of segmental perfusion scores/number of segments]. CMR infarct mass (g) and RT‐MPE myocardial blood flow (MBF dB/s) were quantified. Patients were followed for cardiac events (death, nonfatal MI, revascularization, angina, and heart failure).ResultsAll 27 patients (age 62±14; follow‐up 3.5±2.6 years) had thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct vessel. Cardiac events occurred in 17 (63%). Cardiac event patients had higher PSIRT‐MPE, PSICMR, infarct mass, and lower MBF. PSIRT‐MPE cutoff of 0.3 had an AUC of 0.856 (82% sensitivity, 70% specificity), while a PSICMR cutoff of 0.2 had an AUC of 0.765 (76% sensitivity, 60% specificity). Infarct mass and MBF were independent predictors of cardiac events after adjusting for risk factors (hazard ratios: 20.9 [95% CI 1.8–256] P=.02 and 8.1 [95% CI 1.5–78] P=.01, respectively).ConclusionsQuantitative RT‐MPE performed comparably to CMR for prediction of MACE in STEMI patients supporting a prognostic role for this noninvasive, bedside imaging method.

Objective Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA. Design We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. Results We identified a significant signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate q=0.03), and in gene-level analyses found an association with microsomal glutathione-S-transferase 1 (MGST1); (p=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of these were subsequently confirmed (p<5.5×10−5) in a meta-analysis encompassing an independent set of 1851 BE cases and 3496 controls, and are known strong expression quantitative trait loci for MGST1. Three such variants were associated with similar elevations in OA risk. Conclusions This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/OA and suggests that variants in MGST1 influence disease susceptibility.

BACKGROUNDProspective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study was to investigate the association between lymph node counts from neck dissection, local‐regional recurrence, and overall survival.METHODSThe number of lymph nodes counted from neck dissection in patients treated in 2 NRG Oncology trials (Radiation Therapy Oncology Group [RTOG] 9501 and RTOG 0234) was evaluated for its prognostic impact on overall survival with a multivariate Cox model adjusted for demographic, tumor, and lymph node data and stratified by the postoperative treatment group.RESULTSFive hundred seventy‐two patients were analyzed at a median follow‐up of 8 years. Ninety‐eight percent of the patients were pathologically N+. The median numbers of lymph nodes recorded on the left and right sides were 24 and 25, respectively. The identification of fewer than 18 nodes was associated with worse overall survival in comparison with 18 or more nodes (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09‐1.74; P = .007). The difference appeared to be driven by local‐regional failure (HR, 1.46; 95% CI, 1.02‐2.08; P = .04) but not by distant metastases (HR, 1.08; 95% CI, 0.77‐1.53; P = .65). When the analysis was limited to NRG Oncology RTOG 0234 patients, adding the p16 status to the model did not affect the HR for dissected nodes, and the effect of nodes did not differ with the p16 status.CONCLUSIONSThe removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local‐regional failure, and this should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma. Cancer 2016;122:3464–71. © 2016 American Cancer Society.

Introduction: We aim to describe changes in exercise habits and barriers to physical activity over 5 years in menopausal women at low–intermediate risk for cardiovascular disease. Materials and Methods: Women in the Stress Echocardiography in Menopausal Women at Risk for Coronary Artery Disease trial were prospectively enrolled in a multisite study from 2004 to 2007. Inclusion criteria were as follows: peri- and postmenopausal women with symptoms and/or risk factors for cardiovascular disease resulting in referral for stress echocardiography. A questionnaire, which assessed details of medical history, physical activity, and body mass index (BMI), was administered at baseline and 5 years. Results: 216 menopausal women (62.5% hypertensive, 15.3% diabetic, 52.3% prior or current smokers) were studied. At baseline, age was 54.9 ± 4.8 years, BMI was 30.7 ± 6.4 kg/m 2 , and Framingham risk score was 4.05% ± 3.76%. One hundred women (46.3%) were obese, 79 (36.6%) overweight, and 37 (17.1%) had a normal BMI. Women changed their self-reported aerobic exercise patterns in similar patterns regardless of their BMI at baseline. There was low participation in strength training among all women. Mean BMI decreased by 0.12 kg/m 2 in obese women and increased by 1.63 kg/m 2 in normal BMI women at 5 years ( p < 0.0001). Conclusion: These data suggest that women can increase their level of physical activity regardless of BMI and that overweight or obese status is not a barrier to initiating an aerobic, nonaerobic, or strength training exercise routine.

BACKGROUNDHealth complications related to childhood cancer may be influenced by risky health behaviors (RHBs), particularly when RHBs co‐occur. To the authors' knowledge, only limited information is available describing how RHBs cluster among survivors of childhood cancer and their siblings and the risk factors for co‐occurring RHBs.METHODSLatent class analysis was used to identify RHB clusters using longitudinal survey data regarding smoking, alcohol use, and physical activity from adult survivors (4184 survivors) and siblings (1598 siblings) in the Childhood Cancer Survivor Study. Generalized logistic regression was used to evaluate associations between demographic characteristics, treatment exposures, psychological distress, health conditions, and cluster membership.RESULTSThree RHB clusters were identified: a low‐risk cluster, an insufficiently active cluster, and a high‐risk cluster (tobacco and risky alcohol use and insufficient activity). Compared with siblings, survivors were more likely to be in the insufficiently active cluster (adjusted odds ratio [ORadj], 1.17; 95% confidence interval [95% CI], 1.06‐1.27) and were less likely to be in the high‐risk cluster (ORadj, 0.79; 95% CI, 0.69‐0.88). Risk factors for membership in the high‐risk cluster included psychological distress (ORadj, 2.76; 95% CI, 1.98‐3.86), low educational attainment (ORadj, 7.49; 95% CI, 5.15‐10.88), income <$20,000 (ORadj, 2.62; 95% CI, 1.93‐3.57), being divorced/separated or widowed (ORadj, 1.36; 95% CI, 1.03‐1.79), and limb amputation (ORadj, 1.52; 95% CI, 1.03‐2.24). Risk factors for the insufficiently active cluster included chronic health conditions, psychological distress, low education or income, being obese or overweight, female sex, nonwhite race/ethnicity, single marital status, cranial radiation, and cisplatin exposure.CONCLUSIONSRHBs co‐occur in survivors of childhood cancer and their siblings. Economic and educational disadvantages and psychological distress should be considered in screening and interventions to reduce RHBs. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2747–2756. © 2016 American Cancer Society.

Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focuses on novel and unique aspects of cardiovascular health in women and sex differences as they relate to clinical practice in the prevention, diagnosis, and treatment of cardiovascular disease. This review also provides current approaches to the evaluation and treatment of acute coronary syndromes that are more prevalent in women, including myocardial infarction associated with nonobstructive coronary arteries, spontaneous coronary artery dissection, and stress-induced cardiomyopathy (Takotsubo Syndrome). Other cardiovascular disease entities with higher prevalence or unique considerations in women, such as heart failure with preserved ejection fraction, peripheral arterial disease, and abdominal aortic aneurysms, are also briefly reviewed. Finally, recommendations for cardiac rehabilitation are addressed.

ObjectiveDemonstrate the need for increased education regarding otolaryngology‐related manifestations of human papillomavirus (HPV). Highlight a need to incorporate otolaryngology‐related manifestations of HPV in vaccine counseling.Study DesignSurvey.SettingTertiary care academic children’s hospital.SubjectsPediatric residents, fellows, and staff.MethodsAn online survey was made available regarding HPV education and vaccination.ResultsParticipants (N = 348) initiated the survey representing 28.4%, 25.6%, and 19.0% postgraduate year 1, 2, and 3 residents, respectively, as well as 17.5% chief residents/fellows and 9.5% attendings. Participants rated their prior education as none or fair regarding recurrent respiratory papillomatosis (63.8%) and oropharyngeal squamous cell carcinoma (68.3%). In contrast, 60.6% and 70.9% rated their education on genital warts and cervical cancer correspondingly as good or excellent. When asked what was routinely discussed during HPV vaccine counseling, 63.3% reported “never” discussing recurrent respiratory papillomatosis and 52.9% “never” discussing oropharyngeal squamous cell carcinoma. A range from 92.7% to 95.5% responded that there was a need for increased education regarding HPV and its role in recurrent respiratory papillomatosis and oropharyngeal squamous cell carcinoma.ConclusionsIncreased education about HPV and its otolaryngology‐related manifestations should be undertaken to increase provider, patient, and parent awareness of recurrent respiratory papillomatosis and oropharyngeal squamous cell carcinoma. We propose that discussing the risks of otolaryngology‐related disease be routinely included in HPV vaccination counseling.