Purpose Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance. Experimental Design WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures of the breast (CLS-B). Two independent groups were examined in cross-sectional (Cohort 1) and retrospective (Cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n=10) or treatment (n=90). Metabolic syndrome-associated circulating factors were compared by CLS-B status. The association between CLS-B and the metabolic syndrome was validated in Cohort 2 which included 127 women who developed metastatic breast cancer. Distant recurrence free survival (dRFS) was compared by CLS-B status. Results In Cohorts 1 and 2, breast WAT inflammation was detected in 52/100 (52%) and 52/127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and interleukin-6; and lower HDL cholesterol and adiponectin (P<0.05) in Cohort 1. In Cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P<0.05). Compared to patients without breast WAT inflammation, the adjusted hazard ratio for dRFS was 1.83 (95% CI, 1.07 to 3.13) for patients with inflammation. Conclusions WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis.

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Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen-biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (< 25 kg/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast (CLS-B) which are comprised of dead or dying adipocytes surrounded by macrophages. Severity of inflammation was measured as CLS-B/cm2. The primary objective was to determine if breast WAT inflammation is associated with aromatase expression and activity. Secondary objectives included assessment of circulating factors and breast adipocyte size. Breast WAT inflammation was present in 39% of women. Median BMI was 23.0 (range 18.4 to 24.9) in women with breast WAT inflammation versus 21.8 (range 17.3 to 24.6) in those without inflammation (P=.04). Breast WAT inflammation was associated with elevated aromatase expression and activity, which increased with severity of inflammation (P<.05). Breast WAT inflammation correlated with larger adipocytes (P=.01) and higher circulating levels of C-reactive protein, leptin, insulin, and triglycerides (P≤.05). A subclinical inflammatory state associated with elevated aromatase in the breast, adipocyte hypertrophy, and systemic metabolic dysfunction occurs in some normal BMI women and may contribute to the pathogenesis of breast cancer.

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Elevated aromatase in the setting of adipose dysfunction provides a possible mechanism for the higher incidence of hormone-dependent breast cancer in obese women after menopause.

IMPORTANCE Although leadership behavior of physician supervisors is associated with the occupational well-being of the physicians they supervise, the factors associated with leadership behaviors are poorly understood. OBJECTIVE To evaluate the associations between burnout, professional fulfillment, and self-care practices of physician leaders and their independently assessed leadership behavior scores.

The incidence of inflammatory bowel diseases is increasing worldwide, suggesting a potential role for dietary factors. Here, we demonstrate that a high fructose diet worsens colitis in a microbiota-dependent manner. Overall, this study highlights the importance of diet-microbe interactions in intestinal inflammation. BACKGROUND & AIMS: The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance dextran sodium sulfate (DSS)-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially driven and genetic models of colitis. METHODS: Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histologic analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses, and fecal metabolomics were used to determine microbial composition, spatial distribution, and metabolism. The significance of HFrD on pathogen and genetic-driven models of colitis was determined by using Citrobacter rodentium infection and Il10-/mice, respectively. RESULTS: Reducing or eliminating bacteria attenuated HFrDmediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa

Background Electronic health record (EHR) usability and physician task load both contribute to physician professional burnout. The association between perceived EHR usability and workload has not previously been studied at a national level. Better understanding these interactions could give further information as to the drivers of extraneous task load. Objective This study aimed to determine the relationship between physician-perceived EHR usability and workload by specialty and evaluate for associations with professional burnout. Methods A secondary analysis of a cross-sectional survey of US physicians from all specialties was conducted from October 2017 to March 2018. Among the 1250 physicians invited to respond to the subsurvey analyzed here, 848 (67.8%) completed it. EHR usability was assessed with the System Usability Scale (SUS; range: 0-100). Provider task load (PTL) was assessed using the mental demand, physical demand, temporal demand, and effort required subscales of the National Aeronautics and Space Administration Task Load Index (range: 0-400). Burnout was measured using the Maslach Burnout Inventory. Results The mean scores were 46.1 (SD 22.1) for SUS and 262.5 (SD 71.7) for PTL. On multivariable analysis adjusting for age, gender, relationship status, medical specialty, practice setting, hours worked per week, and number of nights on call per week, physician-rated EHR usability was associated with PTL, with each 1-point increase in SUS score (indicating more favorable) associated with a 0.57-point decrease in PTL score (P<.001). On mediation analysis, higher SUS score was associated with lower PTL score, which was associated with lower odds of burnout. Conclusions A strong association was observed between EHR usability and workload among US physicians, with more favorable usability associated with less workload. Both outcomes were associated with the odds of burnout, with task load acting as a mediator between EHR usability and burnout. Improving EHR usability while decreasing task load has the potential to allow practicing physicians more working memory for medical decision making and patient communication.