Rationale: Recent pediatric studies suggest a survival benefit exists for higher-volume extracorporeal membrane oxygenation (ECMO) centers.Objectives: To determine if higher annual ECMO patient volume is associated with lower case-mix-adjusted hospital mortality rate. Methods:We retrospectively analyzed an international registry of ECMO support from 1989 to 2013. Patients were separated into three age groups: neonatal (0-28 d), pediatric (29 d to ,18 yr), and adult (>18 yr). The measure of hospital ECMO volume was age group-specific and adjusted for patient-level case-mix and hospitallevel variance using multivariable hierarchical logistic regression modeling. The primary outcome was death before hospital discharge. A subgroup analysis was conducted for 2008-2013.Measurements and Main Results: From 1989 to 2013, a total of 290 centers provided ECMO support to 56,222 patients (30,909 neonates, 14,725 children, and 10,588 adults). Annual ECMO mortality rates varied widely across ECMO centers: the interquartile range was 18-50% for neonates, 25-66% for pediatrics, and 33-92% for adults. For 1989-2013, higher age group-specific ECMO volume was associated with lower odds of ECMO mortality for neonates and adults but not for pediatric cases. In 2008-2013, the volume-outcome association remained statistically significant only among adults. Patients receiving ECMO at hospitals with more than 30 adult annual ECMO cases had significantly lower odds of mortality (adjusted odds ratio, 0.61; 95% confidence interval, 0.46-0.80) compared with adults receiving ECMO at hospitals with less than six annual cases.Conclusions: In this international, case-mix-adjusted analysis, higher annual hospital ECMO volume was associated with lower mortality in 1989-2013 for neonates and adults; the association among adults persisted in 2008-2013.

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Objectives We conducted the first empirical examination of disparities in H1N1 exposure, susceptibility to H1N1 complications, and access to health care during the H1N1 influenza pandemic. Methods We conducted a nationally representative survey among a sample drawn from more than 60000 US households. We analyzed responses from 1479 adults, including significant numbers of Blacks and Hispanics. The survey asked respondents about their ability to impose social distance in response to public health recommendations, their chronic health conditions, and their access to health care. Results Risk of exposure to H1N1 was significantly related to race and ethnicity. Spanish-speaking Hispanics were at greatest risk of exposure but were less susceptible to complications from H1N1. Disparities in access to health care remained significant for Spanish-speaking Hispanics after controlling for other demographic factors. We used measures based on prevalence of chronic conditions to determine that Blacks were the most susceptible to complications from H1N1. Conclusions We found significant race/ethnicity-related disparities in potential risk from H1N1 flu. Disparities in the risks of exposure, susceptibility (particularly to severe disease), and access to health care may interact to exacerbate existing health inequalities and contribute to increased morbidity and mortality in these populations.

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Breast cancer is the second-leading cause of cancer-related deaths in women, but the details of how it begins remain elusive. Increasing evidence supports the association of aggressive triple-negative (TN) breast cancer with heightened expression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) and increased tumorinitiating cells (TICs). However, mechanistic links between EZH2 and TICs are unclear, and direct demonstration of a tumorigenic function of EZH2 in vivo is lacking. Here, we identify an unrecognized EZH2/NOTCH1 axis that controls breast TICs in TN breast carcinomas. EZH2 overexpression increases NOTCH1 expression and signaling, and inhibition of NOTCH1 activity prevents EZH2-mediated stem cell expansion in nontumorigenic breast cells. We uncover a unique role of EZH2 in activating, rather than repressing, NOTCH1 signaling through binding to the NOTCH1 promoter in TN breast cancer cells. EZH2 binding is independent of its catalytic histone H3 lysine 27 methyltransferase activity and of the Polycomb Repressive Complex 2 but corresponds instead to transcriptional activation marks. In vivo, EZH2 knockdown decreases the onset and volume of xenografts derived from TN breast TICs. Conversely, transgenic EZH2 overexpression accelerates mammary tumor initiation and increases NOTCH1 activation in mouse mammary tumor virus-neu mice. Consonant with these findings, in clinical samples, high levels of EZH2 are significantly associated with activated NOTCH1 protein and increased TICs in TN invasive carcinomas. These data reveal a functional and mechanistic link between EZH2 levels, NOTCH1 signaling activation, and TICs, and provide previously unidentified evidence that EZH2 enhances breast cancer initiation.

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Background The specific aim of this study was to conduct a systematic review of the literature to assess outcomes data on complications associated with implant-based breast reconstruction performed before or after chest wall radiation to assist in guiding the decision-making process for reconstruction of the radiated breast. Methods Studies from a PubMed search that met predetermined inclusion criteria were identified and included. Complications of interest were low and high grade capsular contractures, minor and major complications, reconstruction failure rates and reconstruction completion rates. Pooled complication rates were calculated. Results A total of 26 articles were included in the study after screening 1,006 publications, with 14 studies presenting data on pre-reconstruction radiation and 23 studies presenting data on post-reconstruction radiation. Complication rates evaluatedin patients exposed to radiation prior to or after implant reconstruction were not significantly different. Reconstruction failure rates were similar at 19% and 20% for pre and post-reconstruction radiation patients respectively. Completion rates were similar at 83% and 80% for pre and post-reconstruction radiation patients respectively. Conclusions Review of the current literature suggests similar overall success and failure rates with pre-reconstruction and post-reconstruction radiation therapy exposure. Failure rates in both groups of patients are clinically significant when considering implant reconstruction in the setting of radiation.

Patients with FM experience increased lifetime levels of psychosocial adversity, trauma, and emotional conflict. To address these risk factors, we developed Emotion Awareness and Expression Therapy (EAET) and tested its benefits against an active control condition, FM Education, and against the field's gold standard intervention for FM, cognitive-behavioral therapy (CBT) for symptom management. Adults with FM (n = 230) formed 40 treatment groups, which were randomized to EAET, CBT, or Education and given eight, 90-min sessions. Patient-reported outcomes were assessed at baseline, post-treatment, and 6-month follow-up (primary endpoint). Retention of patients to follow-up was excellent (90.4%). Intent-to-treat analyses indicated that, although EAET did not differ from FM Education on pain severity (primary outcome), EAET had significantly better outcomes than FM Education on overall symptoms, widespread pain, physical functioning, cognitive dysfunction, anxiety, depression, positive affect, and life satisfaction (between-condition d's ranging from 0.29 to 0.45 SD), and the percentage of patients improving “much/very much” (34.8% vs. 15.4%). EAET did not differ from CBT on the primary or most secondary outcomes, but compared to CBT, EAET led to significantly lower FM symptoms (d = 0.35) and widespread pain (d = 0.37), and a higher percentage of patients achieving 50% pain reduction (22.5% vs. 8.3%). In summary, an intervention targeting emotional awareness and expression related to psychosocial adversity and conflict was well-received, more effective than a basic educational intervention, and had some advantages over CBT on pain. We conclude that EAET should be considered as an additional treatment option for FM.