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Background Fat abnormalities are common among HIV-infected persons, but few studies have compared regional body fat distribution, including visceral fat, in HIV-infected and HIV-uninfected persons and their subsequent trajectories in body composition over time. Methods Between 1999 and 2002, 33 men with clinical evidence of lipodystrophy (LIPO+), 23 HIV-infected men without clinical evidence of lipodytrophy (LIPO-), and 33 HIV-uninfected men were recruited from the four sites of the Multicenter AIDS Cohort Study (MACS). Participants underwent dual-energy x-ray absorptiometry, quantitative computerized tomography of the abdomen and thigh, and circumference measurements of the waist, hip and thigh. Circumference measurements at each semi-annual MACS visit between recruitment and 2008 were used to compare average annual anthropometric changes in the 3 groups. Results Body mass index (BMI) was lower in LIPO+ men than in the LIPO- men and the HIV- uninfected controls (BMI: 23.6 ± 0.4 vs 26.8 ± 1.5 vs 28.7 ± 0.9 kg/m2, respectively, p < 0.001). The average amount of visceral adipose tissue (VAT) was similar in all three groups (p = 0.26), but after adjustment for BMI, VAT was higher in the LIPO+ group (169 ± 10 cm2) compared to the LIPO- men (129 ± 12 cm2, p = 0.03) and the HIV-uninfected group (133 ± 11 cm2, p = 0.07). Subcutaneous adipose tissue (thigh, abdomen) and total extremity fat were less in the HIV-infected men (LIPO+ and LIPO-) than in the HIV-uninfected men. Over an average of 6 years of follow-up, waist circumference increased at a faster rate in LIPO+ group, compared to the LIPO- men (0.51 cm/year vs 0.08 cm/year, p = 0.02) and HIV-uninfected control men (0.21 cm/year, p = 0.06). The annual changes in hip and thigh circumferences were similar in all three groups Conclusion Subcutaneous lipoatrophy was observed in HIV-infected patients, even those without clinical evidence of lipodystrophy, compared to age-matched HIV-uninfected men. Despite markedly lower BMI, HIV-infected men with lipodystrophy had a similar amount of VAT as HIV-uninfected men and tended to have more rapid increases in waist circumference over 6 years of follow-up. These longitudinal increases in waist circumference may contribute to the development of cardiovascular risk in HIV-infected patients with lipodystrophy.

Objective: After menopause, women experience changes in body composition, especially an increase in fat mass. In addition, advancing age, decreased physical activity, and increased inflammation may predispose them to develop type 2 diabetes. Isoflavones have been shown to improve metabolic parameters in postmenopausal women. However, the effect of isoflavones on adipokines/cytokines remains unclear. The purpose of this study was to evaluate the effect of high-dose isoflavones on inflammatory and metabolic markers in postmenopausal women. Methods: We measured glucose, insulin, and adipokines/cytokines in 75 healthy postmenopausal women who were randomized to receive 20 g of soy protein with 160 mg of total isoflavones (64 mg genistein, 63 mg daidzein, and 34 mg glycitein) or 20 g of soy protein placebo for 12 weeks. Women taking estrogen discontinued therapy at least 3 months before the study. The supplements were given in a powder form and consumed once daily with milk or other beverages. Results: Mean ages in the placebo and active groups were similar (P = 0.4). Average time since menopause was 9 years, and two thirds of the women underwent natural menopause. There was no significant difference in body mass index at baseline between the groups (placebo, 25.1 kg/m 2 ; active, 26 kg/m 2 ) and it did not change significantly during the study. At baseline, the placebo group had significantly higher levels of tumor necrosis factor a (P < 0.0001); otherwise, there was no difference in any other parameter. After 12 weeks of treatment, there were significant positive changes in tumor necrosis factor a levels within the placebo group (P < 0.0001) and adiponectin levels within the isoflavone group (P = 0.03). Comparison of pre-post change between the groups showed a small but significant increase in serum adiponectin levels in the isoflavone group (P = 0.03) compared with the placebo group. No significant changes were seen in any other parameter between the two groups. Conclusions: Healthy, normal-weight postmenopausal women may not experience improvement in metabolic parameters when given high-dose isoflavones despite an increase in serum adiponectin levels. The role of isoflavones in obese and insulin-resistant postmenopausal women needs exploration.

The Mann-Whitney-Wilcoxon (MWW) test statistic, while distribution-free, suffers from a loss of efficacy for certain underlying distributions. In this manuscript, we instead use a data-adaptive weighted generalized Mann-Whitney-Wilcoxon (AWGMWW) test statistic, one that is optimal in the Pitman Asymptotic Efficacy (PAE) sense, to discern differences in hippocampus shape among twin populations with or without Major Depressive Disorder (MDD). We verify, based on a previous study using the MWW statistic, that a high-risk group is more similar to the control group than the depressed group in terms of hippocampus shape. In addition, we show that the control group is more similar to the high-risk group than the depressed group - a distinction that could not be made in the preceding study. Our results suggest that the AWGMWW statistic is more powerful for this application.

Purpose Prostate cancer (PCa) is one of the most common cancers in men. Men with recurrent or metastatic PCa are treated with androgen-deprivation therapy (ADT), resulting in profound hypogonadism. Because male hypogonadism is a risk factor for metabolic syndrome and men with PCa have high cardiovascular mortality, we evaluated the prevalence of metabolic syndrome in men undergoing long-term ADT. Patients and Methods This was a cross-sectional study. We evaluated 58 men, including 20 with PCa undergoing ADT for at least 12 months (ADT group), 18 age-matched men with nonmetastatic PCa who had received local treatment and were recently found to have an increasing prostate-specific antigen (non-ADT group), and 20 age-matched controls (control group). Men in the non-ADT and control groups were eugonadal. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Results Mean age was similar among the groups. Men on ADT had significantly higher body mass index and lower total and free testosterone levels. The prevalence of metabolic syndrome was higher in the ADT group compared with the non-ADT (P < .01) and control (P = .03) groups. Among the components of metabolic syndrome, men on ADT had a higher prevalence of abdominal obesity and hyperglycemia. Androgen-deprived men also had elevated triglycerides compared with controls (P = .02). The prevalence of hypertension and low high-density lipoprotein levels were similar. Conclusion These data suggest that metabolic syndrome was present in more than 50% of the men undergoing long-term ADT, predisposing them to higher cardiovascular risk. Abdominal obesity and hyperglycemia were responsible for this higher prevalence. We recommend prospective studies to further delineate this association.

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.

Although Pseudomonas aeruginosa is the most common bacterial infection in adults with cystic fibrosis and frequently develops resistance to multiple classes of antibiotics, it has not been determined whether patients with multiple antibiotic-resistant Pseudomonas aeruginosa have worse clinical outcomes than patients with more susceptible strains.This study assessed the impact of multiply-resistant P. aeruginosa on lung function, hospitalizations, antibiotic use, lung transplantation and survival in adults with cystic fibrosis.In a cohort study at a university-based adult cystic fibrosis program, 75 consecutive adult cystic fibrosis patients who had P. aeruginosa isolated from sputum cultures were studied over a 4-year period. Outcomes included decline in FEV1, clinic visits, hospitalizations, courses and days of intravenous antibiotics, and lung transplantation. Multiple linear and Poisson regression for repeated measures were used to assess the outcomes.In comparison to patients with susceptible strains, patients with resistant P. aeruginosa had more severe baseline lung disease, more rapid decline in FEV1 (160 ml/year, p = 0.003) and were significantly more likely to undergo lung transplantation (17.6 vs. 0%, p = 0.005).Infection with multiple-antibiotic-resistant P. aeruginosa is associated with accelerated progression of cystic fibrosis, and has important implications for infection control strategies, antibiotic use and lung transplantation.

were determined; Bivariate analysiswas used to determinewhether any demographic factors were associated with either youth selfreport or provider documentation. Results: 49/784 (70%) of eligible youth consented, and 85% (n 1⁄4 466) attended the appointment. Mean age was 14.5 (sd 1.6); 65% female, 45 % Hispanic, 38% Black, 17% White. 300/466 (64%) completed the health screening questionnaire. Of those 300 youth who completed the questionnaire, 8.3 % reported having a gun at home, 83.3% reported not having a gun in the home, and 8.3% did not answer the question about firearms. Evaluating provider documentation of firearms in the home, 81% of the time there was no documentation; 17% of the time providers documented that there were not any firearms present, and 1.7% of the time providers documented that therewas a firearm in the home.When therewas actual documentation, 9% of the time providers reported the presence of a firearm. For youth who reported having guns in the home (n 1⁄4 24), 50% of the time providers did not document at all about firearms; 16% of the time there was documentation that there were not firearms when youth reported there were firearms present, and 33% of the time providers documented the presence of firearms. No demographic characteristics, including age, race/ ethnicity, gender or SES were associated with whether youth reported a firearm, or whether a provider documented whether a firearm was present in the home. Conclusions: The vast majority of the time health care providers are not documenting whether there are firearms in the home during routine health care visits. HCPS missed documenting about firearm presence in 67% of youth who report access. However when they did document, they correctly documented 67% of the time. There are significant missed opportunities to counsel families on firearm safety if the topic of firearms is not being addressed during routine health care appointments. Sources of Support: Colorado Injury Control Research Center, Childrens Hospital Colorado Research Institute.

Purpose: Moderate physical activity (PA) has been shown to be beneficial for alleviating some of the symptoms of asthma in teens. Unfortunately, many youth with asthma avoid rigorous PA for fear of an asthma attack. Decreased PA is linked to being overweight or obese. If teens with asthma are at increased risk of being overweight or obese, then it is important to determine if their decreased activity is secondary to their asthma or their weight status. Previous analyses of national data have not accounted for the effect of BMI on PA in asthmatics. Using data from the 2011 Youth Risk Behavior Survey, this study will analyze the association between: (1) asthma and obesity, (2) asthma and PA, and (3) asthma and total sedentary behavior (TSB) in high school adolescents (HSS) while controlling for BMI. Methods: Subjects were in the 9th to 12th grades (N 1⁄4 12286) and were categorized into current asthma (N 1⁄4 1499), past-not current asthma (N1⁄4 1339) and never had asthma groups (N1⁄4 9448) based on their answers to two questions: “Has a doctor or nurse ever told you that you have asthma?” and “Do you still have asthma?”. Primary analyses compared HSS with current asthma with HSS who never had asthma (controls) across the following domains: overweight, obesity, physical activity, and TSB while controlling for age, sex, grade, race/ethnicity and BMI using analyses specifically suited for survey data in SAS 9.2. Overweight was defined by BMI between 85th and 95th %, and obese as> 95th %. Physical activity was assessed with a single question: “During the past 7 days, on how many days were you physically active for a total of at least 60 minutes per day?” TSB was determined by adding the responses to two questions regarding hours spent daily watching television and/or playing video games. Results: 12.6% of HSS reported having current asthma and 76.52% never had asthma (10.90% had past asthma). Asthmatics were more likely to be obese (16.37% vs. 11.84%; adjusted Odds Ratio [aOR]1⁄4 1.513, 95% CI1⁄4 1.248,1.835; p< .0001). A similar trendwas noted for being overweight (aOR 1⁄4 1.17, 0.986, 1.396; p 1⁄4 .07). Teens with current asthma reported having sufficient PA (being physically active for 60 minutes for 5+ days per week) than those who never had asthma (aOR 1⁄4 1.161, 95% CI 1⁄4 1.012, 1.332). Students with current asthma reported being physically active for 60+ minutes on an average of 5.16 (Standard error of mean [SEM] 1⁄4 .10) days per week versus 5.10 (SEM1⁄4 .07) days each week for students without asthma. No significant differences in TSB (1⁄4 5 hours) were found between the two groups. Past asthmatics did not differ from the other groups in any of the outcome variables examined. Conclusions: Studies not controlling for BMI suggest asthmatics are less active than non-asthmatics. Analysis of the 2011 YRBS data shows that teens with asthma, though more likely to be heavy, are no less active than non-asthmatics when adjusted for BMI. Greater efforts to reduce obesity in asthmatics would likely result in even greater PA and overall health. Sources of Support: None. 103.

210 Background: There are known variations in cancer survival based on race and treatment choices. We report the long-term survival probability, based on race, in 16,508 men with localized prostate cancer treated either conservatively or by radiotherapy or radical prostatectomy. Methods: We extracted survival data from tumor registries of six Cancer Research Network sites in the United States. Patients were stratified into four racial groups: Caucasians, African Americans, Hispanics, and Asians. The Cox proportional-hazards regression model was used to compare long-term survival in the three treatment groups. Kaplan-Meier survival curves and competing risk analysis was also performed. Results: Survival was improved for patients who underwent radical prostatectomy compared to radiotherapy or watchful waiting. This was true for all patients combined (Table) as well as for all races individually. Radiotherapy had at least equivalent survival outcomes as watchful waiting in all groups. The differences between treatments were greater for overall survival than for prostate cancer specific survival in all groups, though the extent of the differences varied by race. Conclusions: Radical prostatectomy increases survival in men with localized prostate cancer compared to both radiotherapy and watchful waiting, especially for Caucasian men. Radiotherapy was at least equivalent to watchful waiting for all races. Racial disparities in outcome may influence treatment choices for men with clinically localized prostate cancer. [Table: see text] [Table: see text]

102 Background: The surgical learning curve for robotic assisted laparoscopic radical prostatectomy (RALP) is often cited as being shorter than for other surgical modalities. However, while this appears true with regards to surgical safety, the learning curve for more refined variables like positive surgical margin (PSM) rate and operative time (OT) is not well established. Our objective was to assess the surgical learning curve for RALP in terms of these parameters. Methods: We performed a retrospective cohort study of 3,794 patients who underwent RALP between Jan 2003 and Sep 2009 by three surgeons (DL, PW, AKT) from three centers (UPenn, Karolinska, Cornell). Mean overall PSM rates and mean overall OT were calculated for all three surgeons at intervals of 50 RALPs per surgeon, and learning curves for these means were fit using a loess method. R version 2.71 was used for all statistical analysis. Results: The learning curve for PSM rates for all patients demonstrated improvements that continued with greater surgeon experience, with over 1,600 cases required to get a PSM rate Conclusions: The learning curve for RALP is not as short as previously thought, and a large number of cases are needed to get PSM rates and OTs to a minimum. This suggests that RALP should be performed by high volume surgeons in order to optimize patient outcomes. [Table: see text]

197 Background: There is a paucity of data investigating the relationship between histopathologic variables of oncologic importance and prostate volume, and we aimed to investigate this. Methods: 2,207 consecutive patients who underwent robotic-assisted radical prostatectomy (RARP) were studied. Preoperative demographic and both pre- and post-operative histopathologic parameters were compared among the small prostate (< 40cc), intermediate size (40-70cc), and large prostate (> 70cc) groups. Results: Patients with smaller prostates were younger, had slightly lower BMIs, and lower PSAs than those with smaller prostates (p < 0.001). They also had worse histopathologic criteria (Gleason, core positivity, and maximum percent cancer) on preoperative biopsy and had worse radical specimen Gleason sums (p < 0.001), percent cancer (p < 0.001), and pathologic stage (p = 0.016). 11.5% of men in the small prostate group suffered a positive surgical margin (PSM) compared to 8.3% and 5.6% in the intermediate and large prostate groups, respectively (p = 0.008; Table). Basilar, posterolateral, and multifocal PSMs were commoner in the small prostate group. Conclusions: Younger men have smaller prostates and worse preoperative histopathologic parameters despite lower PSAs. Men with small prostates undergoing RARP have worse final Gleason sums, tumor volume, extraprostatic extension (EPE), and PSM rates than those with larger prostates. We would thus caution against conservative management of men with clinically localized prostate cancer who have small prostates. [Table: see text] No significant financial relationships to disclose.

203 Background: There are no published nomograms that predict prostate cancer in a screened population. We describe three nomograms that predict for prostate cancer on biopsy derived from a large screening population. Methods: Patients from the Tyrol screening study of known age, total prostate-specific antigen (tPSA), digital rectal examination (DRE), prostate volume, and percent free PSA (%fPSA), and who underwent an initial prostate biopsy from January 1992 to June 2004, were included (n=2271). Multivariable logistic regression models were used to develop the biopsy positivity predictive nomograms: nomogram 1- age, DRE, tPSA; nomogram 2- age, DRE, tPSA, prostate volume; nomogram 3- age, DRE, tPSA, prostate volume, %fPSA. The predictive accuracy of the models was assessed in terms of discrimination and calibration. External validation of the nomograms was performed by comparison with a urologically referred population of patients who underwent prostate biopsy (n=599). Results: All three nomograms discriminated well between biopsy positive and biopsy negative patients for both the screening and urologically referred cohorts (nomogram 3 better than nomogram 2 better than nomogram 1). All three nomograms were well calibrated internally, but the nomograms under-predicted the probability of a positive biopsy in the urologically referred cohort. Conclusions: Our nomogram based on age, total PSA, and DRE has a good predictive ability to differentiate between screened patients that will show cancer on initial prostate biopsy and those that will not. Adding prostate volume and percent free PSA improves this predictive power further. All three nomograms under-predict prostate cancer in a urologically referred cohort. These simple nomograms may be of value in counseling screened men with raised PSA and/or abnormal DRE regarding the need for biopsy. No significant financial relationships to disclose.

115 Background: Predictors of biochemical recurrence after robotic-assisted laparoscopic radical prostatectomy (RALP) are not well reported in the literature. We wanted to investigate preoperative predictors as well as the influence of nerve sparing and positive surgical margin status on 3-year biochemical recurrence. Methods: 774 patients with at least 3 year follow up had undergone RALP by a single surgeon at our institution. Biochemcial recurrence was defined as a postoperative PSA >0.2 ng/ml. Multivariable logistic regression models were used to develop the biochemical recurrence predictive nomograms: nomogram 1- age, BMI, PSA density, clinical stage, biopsy Gleason, percent positive cores, perineural invasion; nomogram 2- age, BMI, PSA density, clinical stage, biopsy Gleason, percent positive cores, perineural invasion, nerve sparing, positive surgical margins (none, unifocal, or multifocal). The predictive accuracy of the models was assessed in terms of discrimination and calibration. Results: Both nomograms discriminated well between patients that recurred and those that did not (bootstrap corrected c-indices of 0.766 and 0.806 for nomograms 1 and 2 respectively). Nomogram 1 was well calibrated, but nomogram 2 over- predicted the probability of biochemical recurrence in patients at >30% risk. Conclusions: Our nomogram based on age, BMI, PSA density, clinical stage, biopsy Gleason, percent positive cores, and perineural invasion on preoperative biopsy has a good predictive ability to differentiate between RALP-treated patients that biochemically recur by 3 years from those that do not. Adding nerve sparing and surgical margin status further improved discriminatory ability but at the expense of over-prediction for patients at high risk. These nomograms may be used to guide the use of nerve sparing and the management of positive margins in men undergoing RALP for clinically localized prostate cancer. No significant financial relationships to disclose.