Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.

Young women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH)2D3, reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH)2D3. Treatment with active 1,25(OH)2D3 induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D.

A Geospatial Analysis of the Impact of the Baby-Friendly Hospital Initiative on Breastfeeding Initiation in North Carolina.

BACKGROUND:: Significant disparities in breastfeeding support and practice exist in North Carolina. The Baby-Friendly Hospital Initiative is a worldwide intervention that encourages birth facilities to adopt specific practices in support of breastfeeding. RESEARCH AIM:: This study aimed to evaluate the impact of the Baby-Friendly Hospital Initiative on breastfeeding initiation in North Carolina, with special attention to rural areas. METHODS:: To better understand disparities in breastfeeding initiation across North Carolina, we conducted a secondary analysis of birth certificate data from 2011 to 2014. Univariate and multivariate logistic regression models were used to estimate the association between breastfeeding initiation and (a) birth at a Baby-Friendly hospital and (b) maternal residence in a county with a Baby-Friendly hospital. Model residuals were aggregated by county and analyzed for spatial autocorrelation. RESULTS:: Birth at a Baby-Friendly hospital was associated with increased odds of breastfeeding initiation, adjusted odds ratio = 1.7, 95% confidence interval [1.65, 1.89]. Model residuals showed significant clustering by county, with some rural areas' rates systematically overestimated. Whereas presence of a Baby-Friendly hospital in a mother's community of residence was not associated with increased initiation, birth at a Baby-Friendly hospital was associated with smaller disparities in initiation between rural and urban births. CONCLUSION:: Birth at a Baby-Friendly hospital is associated with improved breastfeeding initiation and reduced disparities in initiation between rural and urban counties in North Carolina.

Management of Intrauterine Contraception in Early Pregnancy.

OBJECTIVES: Women with rare intrauterine contraception (IUC) failures are advised to have their IUC removed because of the risk of poor obstetric outcomes with a retained IUC. Specifics regarding IUC removal in early pregnancy including techniques for removal, rates of success, and immediate pregnancy outcomes following removal are not well described, however. The objective of this study was to identify women with an IUC in early pregnancy examined at a tertiary care center with the primary objective of describing IUC removal attempts, IUC removal successes, and pregnancy outcomes at 20 weeks following IUC removal. METHODS: Case series of women with concurrent IUC and early pregnancy who presented to a tertiary care ultrasound center by 12 weeks' gestation. RESULTS: A total of 3116 women had an early pregnancy ultrasound during the study period. Nineteen (19/3116, 0.61%) women underwent ultrasounds that identified a pregnancy before 12 weeks and an IUC in the uterus. A copper IUC was identified in 11 women (11/19, 58%) on their first ultrasound, and a levonogestrel IUC was identified in 5 women (5/19, 26%). Seventeen (17/19, 88%) women attempted to remove their IUC; 11 of 69 (69%) were successfully removed on the first attempt. Fourteen (14/19; 74%) women with an IUC examined by 12 weeks' gestation had an ongoing pregnancy at 20 weeks compared with 1782 (1782/2678, 67%; P = 0.209) women without an IUC. CONCLUSIONS: Pregnancy with IUC is rare. Among the 19 women who were found to have an in situ IUC and early pregnancy, most had a successful IUC removal and had an ongoing pregnancy at 20 weeks' gestation. In our case series, IUC removal in the first trimester was a straightforward procedure and likely successful.

Pregnancy Outcomes in Patients with Glomerular Disease Attending a Single Academic Center in North Carolina.

BACKGROUND: Contemporary data regarding pregnancy outcomes in US patients with primary glomerular diseases are lacking. We aimed to report fetal and maternal outcomes among women with biopsy-proven primary glomerular disease who received obstetric care at a single large academic US center. METHODS: All women with a biopsy-confirmed primary glomerular disease diagnosis and without end-stage kidney disease who received obstetric care at the University of North Carolina (UNC) Hospitals (1996-2015) were identified using the Glomerular Disease Collaborative Network registry and the UNC Hospitals Perinatal Database. The primary study outcome was perinatal death (stillbirth at >20 weeks or neonatal death). Secondary outcomes included premature birth (<37 weeks), birth weight, preeclampsia, and kidney function changes (postpartum vs. baseline). Demographics, clinical characteristics, and outcomes were compared across glomerular disease subtypes. RESULTS: Among 48 pregnancies in 43 women (IgA nephropathy n = 17, focal segmental glomerulosclerosis [FSGS] n = 16, membranous nephropathy n = 6, minimal change disease n = 4), 13% of pregnancies resulted in perinatal death and 48% of babies were born prematurely. From a maternal perspective, 33% of pregnancies were complicated by preeclampsia, 39% by a doubling of urinary protein, and 27% by a ≥50% increase in serum creatinine. Outcome differences across glomerular disease subtypes were not statistically significant, although decline in kidney function appeared most frequent in FSGS. CONCLUSION: Adverse pregnancy outcomes are frequently observed in women with glomerular disease. The independent influence of glomerular disease subtype on outcomes requires further study. More widespread reporting and analysis of pregnancy outcomes in women with glomerular disease are urgently needed.

Association between hypoalbuminemia and surgical site infection in vulvar cancers.

OBJECTIVE: To determine if preoperative hypoalbuminemia is associated with postoperative wound complications among patients with vulvar cancer. METHODS: The National Surgical Quality Improvement Program database was queried for cases of vulvar cancer undergoing vulvectomy with or without lymphadenectomy (LND) from 2008 to 2013. Primary outcome was major wound complication. Secondary outcome was minor wound complication. Hypoalbuminemia was defined as albumin<3.5g/dL. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of 777 vulvar cancer patients, 514 (66.2%) had vulvar surgery alone and 263 (30.3%) had a LND. Median age was 66 (range 20-90) and median BMI was 28.9kg/m(2) (range 14.3-65.5). The incidence of wound complication was 10.4% (81/777) with 48 minor and 39 major complications. There was no difference in major wound complications when a LND was performed (p=1.0). Preoperative albumin was recorded in 429 patients (55.2%). Patients with hypoalbuminemia were more likely to have a major wound complication (OR 2.9 95% CI 1.1-7.3, p=0.02), even after adjusting for BMI, age, preoperative hematocrit, and diabetes (aOR 2.7 95% CI 1.1-7.1, p=0.04). In bivariable analysis, age, diabetes, and BMI were not associated with wound complication. Patients with a wound infection had 10 times the odds of being readmitted within 30days (OR 9.5, 95% CI 4.9-18.4, p<0.01). CONCLUSIONS: Low preoperative albumin is associated with major postoperative wound complications in women undergoing surgery for vulvar cancer. When obtaining informed consent, patients with low albumin should be counseled regarding higher risks of postoperative wound complication.

Patient characteristics associated with treatment choice for pelvic organ prolapse and urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Women with pelvic organ prolapse (POP) and stress urinary incontinence (SUI) frequently undergo more than one treatment prior to settling on their final strategy. We hypothesize that women who are younger, with worse POP and SUI symptoms will desire and choose surgical treatment. METHODS: A retrospective cohort study was performed over 1 year identifying new patients presenting with POP and/or SUI at a university hospital. Our aim was to determine patient desire for either surgical or conservative treatment, as well as the actual treatment chosen and received after the first visit and 1 year later. To identify predictors of choice, baseline demographic characteristics were obtained. RESULTS: Of the 203 women who met the inclusion criteria, 44.3 % (90/203) desired surgery and 55.7 % (113/203) desired conservative treatment at their first visit. Women who desired surgery were more likely to be younger (p = 0.003), sexually active (p = 0.001), have more advanced prolapse (p = 0.006), and have more bothersome symptoms (p = 0.05). Of the women who desired surgery at their first visit, 12.2 % (11/90) actually chose conservative treatment. These women were less likely to be insured (p = 0.01). By 1 year, of the women who initially desired and subsequently chose conservative treatment, 26.5 % (30/113) had undergone surgery. The women who changed from conservative to surgical treatment were more likely to be younger (p = 0.01), non-White (p = 0.03), and sexually active (p = 0.04). CONCLUSIONS: In this study, younger, sexually active women were more likely to either opt for surgery initially or to change their treatment plan from conservative to surgical.

Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection.

HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10(-4)) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4(+) T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4(+) T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir.