Association of Antibody Immunity With Cryptococcal Antigenemia and Mortality in a South African Cohort With Advanced Human Immunodeficiency Virus Disease.

BACKGROUND: Asymptomatic cryptococcal antigenemia (positive blood cryptococcal antigen [CrAg]) is associated with increased mortality in individuals with human immunodeficiency virus (HIV) even after adjusting for CD4 count and despite receiving antifungal treatment. The association of antibody immunity with mortality in adults with HIV with cryptococcal antigenemia is unknown. METHODS: Cryptococcal capsular glucuronoxylomannan (GXM)- and naturally occurring ß-glucans (laminarin, curdlan)-binding antibodies were measured in blood samples of 197 South Africans with HIV who underwent CrAg screening and were followed up to 6 months. Associations between antibody titers, CrAg status, and all-cause mortality were sought using logistic and Cox regression, respectively. RESULTS: Compared with CrAg-negative individuals (n = 130), CrAg-positive individuals (n = 67) had significantly higher IgG1 (median, 6672; interquartile range [IQR], 4696-10 414 vs 5343, 3808-7722 µg/mL; P = .007), IgG2 (1467, 813-2607 vs 1036, 519-2012 µg/mL; P = .01), and GXM-IgG (1:170, 61-412 vs 1:117, 47-176; P = .0009) and lower curdlan-IgG (1:47, 11-133 vs 1:93, 40-206; P = .01) titers. GXM-IgG was associated directly with cryptococcal antigenemia adjusted for CD4 count and antiretroviral therapy use (odds ratio, 1.64; 95% confidence interval [CI], 1.21 to 2.22). Among CrAg-positive individuals, GXM-IgG was inversely associated with mortality at 6 months adjusted for CD4 count and tuberculosis (hazard ratio, 0.50; 95% CI, .33 to .77). CONCLUSIONS: The inverse association of GXM-IgG with mortality in CrAg-positive individuals suggests that GXM-IgG titer may have prognostic value in those individuals. Prospective longitudinal studies to investigate this hypothesis and identify mechanisms by which antibody may protect against mortality are warranted.

Association of fractional exhaled nitric oxide with asthma morbidity in urban minority children.

OBJECTIVE: Fractional exhaled nitric oxide (FeNO) is a well-established measure of allergic airway inflammation and possible useful adjunct disease management tool. We investigated the association of baseline and follow-up FeNO measurements with disease burden in minority children with persistent asthma. METHODS: A retrospective chart review was conducted on 352 African American and Hispanic children seen at an urban Asthma Center in Bronx, NY. Demographic, clinical characteristics, and pulmonary function tests (PFTs) were compared between children with low, intermediate, and high baseline FeNO levels. Among 95 children with subsequent follow up visits, associations of change in FeNO with demographics, clinical characteristics, and PFTs were examined using mixed effects linear regression models. RESULTS: A higher proportion of children with intermediate (54%) and high FeNO (58%) levels had lower airways obstruction compared to those with low FeNO levels (33%). Children with intermediate FeNO levels had more annual hospitalizations (2.8 ± 6.2) compared to those with low and high FeNO levels (1.3 ± 2.8 and 1.3 ± 2.5). These associations did not differ between ethnicities. An increase in FeNO over time was associated with higher BMI z-scores (ß = 6.2, 95% CI: 1.0 to 11.4) and two or more hospitalizations in the past year (ß = 16.1, 95% CI: 1.5 to 30.8). CONCLUSIONS: Intermediate and high FeNO levels are associated with lower airways obstruction and hospitalizations. Initial and serial FeNO measurements can be a useful adjunctive tool in identifying asthma-related morbidity in urban African American and Hispanic children.

Reduced kidney function and hypertension in adolescents with low birth weight, NHANES 1999-2016.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem, and the risk of CKD and hypertension in children born low birth weight (LBW) is under-recognized. We hypothesized that children born with LBW would have a higher prevalence of reduced kidney function and hypertension. METHODS: Using the National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study to evaluate whether LBW (< 2500 g), very low birth weight (VLBW < 1500 g), and large birth weight (BW) (> 4000 g) were associated with kidney disease using 4 different estimating equations. We used the Counahan-Barratt, updated Schwartz, CKiD-U25, and full age spectrum creatinine-based GFR estimating equations to evaluate associations between a history of LBW/VLBW/large BW and reduced kidney function (eGFR < 90 mL/min/1.73 m2) in children. We also assessed blood pressure (BP) using the old and new pediatric hypertension guidelines. RESULTS: Our analysis included 6336 children (age 12-15 years) in NHANES representing over 13 million US individuals. Using the updated Schwartz, the prevalence of reduced kidney function was 30.1% (25.2-35.6) for children born with LBW compared to 22.4% (20.5-24.3) in children with normal BW. Equations yielded different estimates of prevalence of reduced kidney function in LBW from 21.5% for Counahan-Barratt to 35.4% for CKiD-U25. Compared to those with normal BW, participants with LBW and VLBW had a 7.2 and 10.3% higher prevalence of elevated BP and a 2.4 and 14.6% higher prevalence of hypertension, respectively. CONCLUSIONS: Children born with LBW are at higher risk of reduced kidney function and hypertension than previously described. A higher resolution version of the Graphical abstract is available as Supplementary information.

Overall and central obesity and prostate cancer risk in African men.

PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multi-center, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI ≥ 30 kg/m2), 26% and 90% had WC > 97 cm and WHR > 0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive PCa, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR = 1.38, 95% CI 0.99-1.93), and central obesity (WC > 97 cm: OR = 1.60, 95% CI 1.10-2.33; and WHtR > 0.59: OR = 1.68, 95% CI 1.24-2.29) were positively associated with D'Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

The impact of surgical downgrading on prostate cancer recurrence: systematic review and analysis of a multiethnic population.

OBJECTIVE: To perform a systematic review and a retrospective cohort analysis evaluating the rates of surgical downgrading of prostate cancer (PCa) from biopsy (PBx) to radical prostatectomy (RP), and their association with biochemical recurrence (BCR) in a multiethnic population. METHODS: A systematic review of PubMed and other databases was performed. We included retrospective studies evaluating the relationship between surgical downgrading and BCR-free survival. Data regarding Gleason score (GL) downgrading were abstracted from the articles and categorized as follows: GL8-10 to GL7, GL7 to GL6, and GL 7(4 + 3) to GL7(3 + 4). We also performed a retrospective cohort review of patients who underwent RP at our institution from 2005 through 2020. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare BCR among downgraded versus non-downgraded men. RESULTS: Systematic review yielded 137 abstracts; of these, 36 full-texts were reviewed, 8 of which were included in our systematic review. Despite substantial variability, all showed that GL at RP is one of the most important factors of BCR-free survival. A total of 1,484 men with PCa were analyzed from our institution. On multivariate analysis, GL7 to GL6 downgrading (HR = 0.50, p = 0.022) and GL8-10 to GL7 downgrading (HR = 0.42, p = 0.011) were associated with reduced risk of BCR when compared to men with GL7 and GL8-10 concordance, respectively. However, GL7(4 + 3) to GL7(3 + 4) downgrading was not significantly associated with reduced BCR (HR = 0.56, p = 0.12), when compared to GL7(4 + 3) concordance, although HR was similar. CONCLUSION: Surgical downgrading at RP was associated with a reduced risk of BCR compared to GL concordant disease, and these findings have been validated within our multiethnic population. Pathologic downgrading at the time of RP may be a more useful predictor of subsequent BCR in comparison to that associated with GL concordant pathology.

A Comparison of Image-Guided Targeted Prostate Biopsy Outcomes by PI-RADS® Score and Ethnicity in a Diverse, Multiethnic Population.

PURPOSE: NonHispanic Black (NHB) and Hispanic/Afro-Caribbean men have the highest risk of prostate cancer (PCa) compared to nonHispanic White (NHW) men. However, ethnicity-specific outcomes of targeted fusion biopsy (FB) for the detection of PCa are poorly characterized. We compared the outcomes of FB by Prostate Imaging Reporting and Data System (PI-RADS®) score and race/ethnicity among a diverse population. MATERIALS AND METHODS: We evaluated all men who underwent image-guided FB for suspicious lesions on prostate magnetic resonance imaging (≥PI-RADS 3) over a 2-year period. We examined associations of race/ethnicity and PI-RADS score with risk of PCa or clinically significant PCa (cs-PCa, Gleason Group ≥2) on FB using mixed-effects logistic regression models. RESULTS: A total of 410 men with 658 lesions were analyzed, with 201 (49.0%) identified as NHB and 125 (30.5%) identified as Hispanic. NHB men had a twofold increase in the odds of detecting cs-PCa (OR=2.7, p=0.045), while Hispanic men had similar odds of detecting cs-PCa compared to NHW men. With regard to all PCa, NHB men had a similar increase in the odds of detecting all PCa (OR=2.4, p=0.050), which was borderline statistically significant compared to NHW men on FB. When we excluded men on active surveillance, NHB men had even stronger associations with detection of cs-PCa (OR=3.10, p=0.047) or all PCa (OR=2.77, p=0.032) compared to NHW men. CONCLUSIONS: NHB men have higher odds for overall PCa and cs-PCa on FB compared to NHW men. Further work may clarify differences per PI-RADS score. Clinicians should interpret prostate magnetic resonance imaging lesions with more caution in NHB men.

Finasteride Use and Risk of Bladder Cancer in a Multiethnic Population.

PURPOSE: Finasteride use has been associated with a reduced incidence of bladder cancer. However, the majority of studies have been conducted primarily in East Asian or White populations. Given differences in the incidence of bladder cancer among racial/ethnic groups, it is important to determine whether the effect of finasteride use on bladder cancer varies by race/ethnicity. MATERIALS AND METHODS: We identified all patients with a diagnosis of benign prostatic hyperplasia between 2000 and 2016 at our academic health center in Bronx, New York via an electronic medical record database. We then identified patients who were prescribed finasteride, and those who developed bladder cancer during followup. We used competing risk analysis to examine associations of finasteride use with risk of bladder cancer, adjusting for age, smoking and race/ethnicity. RESULTS: We identified 42,406 patients with benign prostatic hyperplasia (average±SD age 67±12.9 years), of whom 27.7% were Black and 14.8% were Hispanic. Finasteride was prescribed in 5,698 patients (13.4%). Bladder cancer was diagnosed in 84 of 5,698 finasteride users (1.5%), compared to 762 of 36,708 nonusers (2.1%, log-rank p=0.003). Finasteride was associated with a 36% reduction in risk of bladder cancer (HR: 0.64, 95% CI: 0.51-0.80; p <0.0001) among all patients. When data were stratified by race/ethnicity, finasteride use was associated with a reduction in risk of bladder cancer in White men (HR: 0.61, 95% CI: 0.43-0.86; p=0.005) and Hispanic men (HR: 0.44, 95% CI: 0.21-0.90; p=0.026), but there was no association among Black men (HR: 1.01, 95% CI: 0.67-1.51; p=0.964). CONCLUSIONS: Our study corroborates previous findings that men who are on finasteride have a lower bladder cancer incidence. However, the reduction in risk was seen only in White and Hispanic men, but not among Black men. Therefore, race/ethnicity represents an important stratification factor for future larger studies on finasteride as chemoprevention for bladder cancer.

Endothelial Wnt/ß-catenin signaling reduces immune cell infiltration in multiple sclerosis.

Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/ß-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear. Using a Wnt/ß-catenin reporter mouse and several downstream targets, we demonstrate that the Wnt/ß-catenin pathway is up-regulated in CNS endothelial cells in both human MS and the mouse model experimental autoimmune encephalomyelitis (EAE). Increased Wnt/ß-catenin activity in CNS blood vessels during EAE progression correlates with up-regulation of neuronal Wnt3 expression, as well as breakdown of endothelial cell junctions. Genetic inhibition of the Wnt/ß-catenin pathway in CNS endothelium before disease onset exacerbates the clinical presentation of EAE, CD4+ T-cell infiltration into the CNS, and demyelination by increasing expression of vascular cell adhesion molecule-1 and the transcytosis protein Caveolin-1 and promoting endothelial transcytosis. However, Wnt signaling attenuation does not affect the progressive degradation of tight junction proteins or paracellular BBB leakage. These results suggest that reactivation of Wnt/ß-catenin signaling in CNS vessels during EAE/MS partially restores functional BBB integrity and limits immune cell infiltration into the CNS.

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls.

BACKGROUND: Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. METHODS: Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients. RESULTS: Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPD patients. CONCLUSIONS: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers. © 2019 International Parkinson and Movement Disorder Society.

Opioid prescribing practices and medication use following urogynecological surgery.

BACKGROUND: Opioid abuse is a growing epidemic in the United States, with opioid overdose becoming a leading cause of death. There is wide variation in prescription practices for post-operative opioids due to absence of guidelines. The purpose of this study is to examine postoperative opioid prescribing patterns after urogynecologic surgery and determine usage and management of opioid pills by patients. MATERIALS AND METHODS: This is an observational, prospective study of female patients (N = 143) who underwent urogynecologic (prolapse or incontinence) surgery from June to December 2017 at a single academic center. Patients were surveyed regarding their pain medication use 30 days postoperatively. Survey questions included preoperative pain medication use, quantity of opioid pills consumed, need for additional opioid prescription, and management of remaining pills. T-test and one-way Anova were used for comparison of continuous variables and chi-squared test used for comparison of categorical variables. RESULTS: Of 143 eligible patients, 99 (69%) responded; 62% of respondent patients underwent vaginal surgery, 22% abdominal surgery with or without vaginal surgery, and 15% underwent other procedures. Postoperatively, 81.8% of patients were prescribed opioids. The average number of tablets prescribed ranged from 12.4 to 17.4 depending on the procedure. 54.3% of patients reported using less than half of their prescribed opioid prescription. Of the patients who had excess opioid tablets, only 8.6% reported discarding their opioids. CONCLUSION: To date, no guidelines exist on prescribing opioids postoperatively. Opioids are overprescribed post-operatively with over half of patients using less than half of the opioids prescribed to them.

Identification and characterization of RSIY-11, a novel seminal peptide derived from semenogelin-1, which acts as a neutral endopeptidase inhibitor modulating sperm motility.

PURPOSE: Based on prior reports demonstrating that neutral endopeptidase (NEP) inhibitors increase sperm motility, the goal of our studies was to identify endogenous seminal peptides that inhibit NEP and investigate their potential effect on sperm motility. METHODS: Peptidomic analysis was performed on human seminal fluid, identifying 22 novel peptides. One peptide, named RSIY-11, derived from semenogelin-1, was predicted through sequence analysis to be a substrate and/or potential inhibitor of NEP. Enzymatic analysis was conducted to determine the inhibitory constant (Ki) of RSIY-11 as an inhibitor of NEP. Total and progressive sperm motility was determined at baseline and 30 and 60 min following addition of RSIY-11 to seminal fluid in 59 patients undergoing an infertility workup at an urban medical center. Additionally, the effects of RSIY-11 on sperm motility were evaluated in 15 of the 59 patients that met criteria for asthenospermia. RESULTS: RSIY-11 was shown to act as a competitive inhibitor of NEP with a Ki of 18.4 ± 1.6 µM. Addition of RSIY-11 at concentrations of 0.75 µM, 7.5 µM, and 75 µM significantly increased sperm motility at all time points investigated, with increases of 6.1%, 6.9%, and 9.2% at 60 min, respectively. Additionally, within the subgroup of patients with asthenospermia, RSIY-11 at concentrations of 0.75 µM, 7.5 µM, and 75 µM significantly increased sperm motility at all time points investigated, with increases of 7.6%, 8.8%, and 10.6% at 60 min, respectively. CONCLUSIONS: RSIY-11 is a newly identified semenogelin-1-derived peptide present in seminal fluid. RSIY-11 acts as a potent competitive inhibitor of NEP, which when added to seminal fluid significantly increases sperm motility. RSIY-11 could play a potential role in the treatment for male factor infertility related to asthenospermia and improve intrauterine insemination outcomes.

Improving outcomes in cancer diagnosis, prevention and control: barriers, facilitators and the need for health literacy in Ibadan Nigeria.

BACKGROUND: Cancers constitute a significant public health problem in Nigeria. Breast, cervix and prostate cancers are leading causes of cancer-related deaths. Changing diets, lifestyles, HIV/AIDS and macro-structural factors contribute to cancer morbidity and mortality. Poor health information linking cancer risk to individual behaviors, environmental pollutants and structural barriers undermine prevention/control efforts. Studies suggest increasing health literacy and empowering individuals to take preventive action will improve outcomes and mitigate impact on a weak health system. METHODS: We obtained qualitative data from 80 men, women, and young adults in 11 focus groups to assess beliefs, risk-perceptions, preventive behaviors and perceptions of barriers and facilitators to cancer control in Ibadan, Nigeria and conducted thematic analysis. RESULTS: Participants demonstrated awareness of cancers and mentioned several risk factors related to individual behaviors and the environment. Nonetheless, myths and misconceptions as well as micro, meso and macro level barriers impede prevention and control efforts. CONCLUSION: Developing and implementing comprehensive context-relevant health literacy interventions in community settings are urgently needed.Copyright © 2016 John Wiley & Sons, Ltd.

New methods for estimating follow-up rates in cohort studies.

BACKGROUND: The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the "Percentage Method", defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark's Completeness Index (CCI) also have limitations. METHODS: We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT) in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT) that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset. RESULTS: Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%). CONCLUSIONS: The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and dropout rates are high.

A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer.

Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy.

Familial clustering of breast and prostate cancer and risk of postmenopausal breast cancer in the Women's Health Initiative Study.

BACKGROUND: Evidence suggests that the risk of breast and prostate cancer is increased among those with a family history of the same disease and particularly among first-degree relatives. However, less is known about the relationship between breast and prostate cancer within families and particularly among minority populations. METHODS: Analyses of participants in the Women's Health Initiative observational cohort who were free of breast cancer at the time of their baseline examination were conducted. Subjects were followed for breast cancer through August 31, 2009. A Cox proportional hazards regression modeling approach was used to estimate the risk of breast cancer associated with a family history of prostate cancer, breast cancer, and both among first-degree relatives. RESULTS: There were 78,171 eligible participants, and 3506 breast cancer cases were diagnosed during the study period. A family history of prostate cancer was associated with a modest increase in breast cancer risk after adjustments for confounders (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.02-1.26). In a separate analysis examining the joint impact of both cancers, a family history of both breast and prostate cancer was associated with a 78% increase in breast cancer risk (aHR, 1.78; 95% CI, 1.45-2.19). Risk estimates associated with a family history of both breast and prostate cancer were higher among African American women (aHR, 2.34; 95% CI, 1.09-5.02) versus white women (aHR, 1.66; 95% CI, 1.33-2.08). CONCLUSIONS: These findings suggest that prostate cancer diagnosed among first-degree family members increases a woman's risk of developing breast cancer. Future studies are needed to determine the relative contributions of genes and a shared environment to the risk for both cancers.

The impact of obesity on prostate cancer recurrence observed after exclusion of diabetics.

PURPOSE: Although overall there is a positive association between obesity and risk of prostate cancer (PrCa) recurrence, results of individual studies are somewhat inconsistent. We investigated whether the failure to exclude diabetics in prior studies could have increased the likelihood of conflicting results. METHODS: A total of 610 PrCa patients who underwent radical prostatectomy between 2005 and 2012 were followed for recurrence, defined as a rise in serum PSA ≥ 0.2 ng/ml following surgery. Body mass index (BMI) and history of type 2 diabetes were documented prior to PrCa surgery. The analysis was conducted using Cox proportional hazard models. RESULTS: Obesity (25.6 %) and diabetes (18.7 %) were common in this cohort. There were 87 (14.3 %) recurrence events during a median follow-up of 30.8 months after surgery among the 610 patients. When analyzed among all PrCa patients, no association was observed between BMI/obesity and PrCa recurrence. However, when analysis was limited to non-diabetics, obese men had a 2.27-fold increased risk (95 % CI 1.17-4.41) of PrCa recurrence relative to normal weight men, after adjusting for age and clinical/pathological tumor characteristics. CONCLUSIONS: This study found a greater than twofold association between obesity/BMI and PrCa recurrence in non-diabetics. We anticipated these results because the relationship between BMI/obesity and the biologic factors that may underlie the PrCa recurrence-BMI/obesity association, such as insulin, may be altered by the use of anti-diabetes medication or diminished beta-cell insulin production in advanced diabetes. Studies to further assess the molecular factors that explain the BMI/obesity-PrCa recurrence relationship are warranted.

The feasibility of epidemiological research on prostate cancer in African men in Ibadan, Nigeria.

BACKGROUND: Men of African descent have the highest incidence and mortality rates of prostate cancer (PrCa) worldwide. Notably, PrCa is increasing in Africa with Nigerian men being mostly affected. Thus, it is important to understand risk factors for PrCa in Nigeria and build capacity for cancer research. The goals of this study were to determine the feasibility of conducting an epidemiological study of PrCa and to obtain preliminary data on risk factors for PrCa in Nigeria. METHODS: A case-control study (50 cases/50 controls) was conducted at the University College Hospital (UCH) in Ibadan, Nigeria, between October 2011 and December 2012. Men aged 40 to 80 years were approached for the study and asked to provide informed consent and complete the research protocol. Logistic regression models were used to examine associations between demographic, social and lifestyle characteristics and risk of PrCa. RESULTS: The participation rate among cases and controls was 98% and 93%, respectively. All participants completed a questionnaire and 99% (50 cases/49 controls) provided blood samples. Cases had a median serum diagnostic PSA of 73 ng/ml, and 38% had a Gleason score 8-10 tumor. Family history of PrCa was associated with a 4.9-fold increased risk of PrCa (95% CI 1.0 - 24.8). There were statistically significant inverse associations between PrCa and height, weight and waist circumference, but there was no association with body mass index (kg/m(2)). There were no associations between other socio-demographic and lifestyle characteristics and PrCa risk. CONCLUSION: This feasibility study demonstrated the ability to ascertain and recruit participants at UCH and collect epidemiological, clinical and biospecimen data. Our results highlighted the advanced clinical characteristics of PrCa in Nigerian men, and that family history of PrCa and some anthropometric factors were associated with PrCa risk in this population. However, larger studies are needed to better understand the epidemiological risk factors of PrCa in Nigeria.

Relationship of ultraviolet light exposure and cutaneous and systemic disease activity in youth with childhood-onset systemic lupus: Results from the Childhood Arthritis and Rheumatology Research Alliance Registry.

Objective: To investigate the association between sun exposure measured by ultraviolet light index (UVI) and seasonality with rash and systemic disease activity in youth with childhood-onset systemic lupus (cSLE) from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods: We reviewed data on rash and disease activity from Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from cSLE CARRA Registry participants with visits between 2010 and 2019 and obtained UVI data from the National Oceanic and Atmospheric Administration (NOAA). Our main exposures were UVI and season during the month of visit and one month prior to visit. We used mixed-effects logistic regression to examine an association between UVI/season and rash / SLEDAI-2K score, adjusting for age, sex, race and income. Results: Among 1222 participants, with a mean of 2.3 visits/participant, 437 visits (15%) had rash and 860 (30%) had SLEDAI-2K score ≥ 5. There were no associations between UVI during the month prior to visit, or the month of the visit and odds of rash or elevated systemic activity. However, fall season was associated with increased odds of rash (OR = 1.59, p = 0.04), but there not increased disease activity. Conclusion: While we found no association between UVI and rash or UVI and disease activity, further studies directly measuring UVI may help further understand whether a relationship exists between sun exposure and SLE disease activity and whether this is an area that continues to require clinical attention.

Relationship of regional ultraviolet index data with rash and systemic disease activity in youth with childhood-onset systemic lupus: results from the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To investigate the association between ultraviolet light index (UVI), as a marker for UV exposure, and seasonality with rash and systemic disease activity in youth with childhood-onset systemic lupus (cSLE) from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. METHODS: We reviewed data on rash and disease activity from Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores from cSLE CARRA Registry participants with visits between 2010 and 2019 and obtained zipcode level UVI data from the National Oceanic and Atmospheric Administration (NOAA). Our main exposures were UVI and season during the month of visit and one month prior to visit. We used mixed-effects logistic regression models to examine associations between regional UVI (by zipcode)/season and odds of rash and severe SLEDAI-2 K score (≥ 5 vs. 0-4), adjusting for age, sex, race and income. RESULTS: Among 1222 participants, with a mean of 2.3 visits per participant, 437 visits (15%) had rash and 860 (30%) had SLEDAI-2 K score ≥ 5. There were no associations between UVI during the month prior to visit or the month of the visit and odds of rash or elevated systemic activity. However, fall season was associated with increased odds of rash (OR = 1.59, p = 0.04), but not increased disease activity. CONCLUSION: This study found no association between UVI and rash or UVI and disease activity. However, further studies directly measuring UV exposure and accounting for patient-level protective behavioral measures may help to better understand the complex relationship between sun exposure and SLE disease activity.