Christina Pinkston

Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation

Although combination simeprevir (SIM) plus sofosbuvir (SOF) is an approved regimen for genotype 1 chronic hepatitis C virus (HCV), data regarding its safety and efficacy in liver transplant recipients remain limited. A multicenter retrospective study was performed to determine the efficacy and tolerability of a 12‐week regimen of SIM/SOF with or without ribavirin (RBV) in 56 consecutive liver transplant recipients in 2014; 79% of patients had genotype 1a, 14% had cirrhosis, and 73% were treatment experienced. Sustained virological response at 12 weeks (SVR12) was 88% by intention to treat analysis (95% confidence interval, 84%‐90%). Four patients relapsed, but no on‐treatment virological failures occurred. The Q80K polymorphism did not impact SVR12, but there was a trend toward decreased sustained virological response with advanced fibrosis (P = 0.18). HCV RNA was detectable at treatment week 4 in 21% of patients, and those who had detectable levels were less likely to achieve SVR12 (58% versus 95%; P = 0.003). Five patients had baseline Child‐Pugh class B cirrhosis, and 2 of them died (1 following early discontinuation of therapy). An additional discontinuation resulted from a severe photosensitivity reaction in a patient on concomitant cyclosporine. Seven patients receiving RBV developed progressive anemia requiring intervention. Immunosuppression dose modifications were minimal. SIM/SOF for 12 weeks was effective and well tolerated by compensated liver transplant recipients especially when administered without concomitant RBV or cyclosporine. SIM/SOF appears to have a niche as the only 12‐week RBV‐free treatment regimen currently recommended by guidelines for compensated transplant recipients. However, 12 weeks may not be the optimal duration of therapy for those with detectable virus at week 4 or possibly for those with cirrhosis. These data require confirmation by prospective randomized clinical trials. Liver Transplantation 22 635‐643 2016 AASLD.

Obesity and Risk of Breast Cancer Mortality in Hispanic and Non-Hispanic White Women: The New Mexico Women's Health Study

Obesity is reported to be associated with poorer survival in women with breast cancer, regardless of menopausal status. Our purpose was to determine if the associations of obesity with breast cancer-specific, all-cause, and non-breast cancer mortality differ between Hispanic and non-Hispanic white (NHW) women with breast cancer. Data on lifestyle and medical history were collected for incident primary breast cancer cases (298 NHW, 279 Hispanic) in the New Mexico Womens Health Study. Mortality was ascertained through the National Death Index and New Mexico Tumor Registry over 13 years of follow-up. Adjusted Cox regression models indicated a trend towards increased risk for breast cancer-specific mortality in obese NHW women (hazard ratio [HR] 2.07; 95% confidence interval [CI] 0.98-4.35) but not in Hispanic women (HR 1.32; 95% CI 0.64-2.74). Obese NHW women had a statistically significant increased risk for all-cause mortality (HR 2.12; 95% CI 1.15-3.90) while Hispanic women did not (HR 1.23; 95% CI 0.71-2.12). Results were similar for non-breast cancer mortality: NHW (HR 2.65; 95% CI 0.90-7.81); Hispanic (HR 2.18; 95% CI 0.77-6.10). Our results suggest that obesity is associated with increased risk for breast cancer-specific mortality in NHW women; however, this association is attenuated in Hispanic women.

Associations between ALOX, COX, and CRP polymorphisms and breast cancer among Hispanic and non-Hispanic white women: The breast cancer health disparities study

Chronic inflammation is suggested to be associated with specific cancer sites, including breast cancer. Recent research has focused on the roles of genes involved in the leukotriene/lipoxygenase and prostaglandin/cyclooxygenase pathways in breast cancer etiology. We hypothesized that genes in ALOX/COX pathways and CRP polymorphisms would be associated with breast cancer risk and mortality in our sample of Hispanic/Native American (NA) (1430 cases, 1599 controls) and non‐Hispanic white (NHW) (2093 cases, 2610 controls) women. A total of 104 Ancestral Informative Markers was used to distinguish European and NA ancestry. The adaptive rank truncated product (ARTP) method was used to determine the significance of associations for each gene and the inflammation pathway with breast cancer risk and by NA ancestry. Overall, the pathway was associated with breast cancer risk (PARTP = 0.01). Two‐way interactions with NA ancestry (Padj < 0.05) were observed for ALOX12 (rs2292350, rs2271316) and PTGS1 (rs10306194). We observed increases in breast cancer risk in stratified analyses by tertiles of polyunsaturated fat intake for ALOX12 polymorphisms; the largest increase in risk was among women in the highest tertile with ALOX12 rs9904779CC (Odds Ratio (OR), 1.49; 95% Confidence Interval (CI) 1.14‐1.94, Padj = 0.01). In a sub‐analysis stratified by NSAIDs use, two‐way interactions with NSAIDs use were found for ALOX12 rs9904779 (Padj = 0.02), rs434473 (Padj = 0.02), and rs1126667 (Padj =  0.01); ORs for ALOX12 polymorphisms ranged from 1.55 to 1.64 among regular users. Associations were not observed with breast cancer mortality. These findings could support advances in the discovery of new pathways related to inflammation for breast cancer treatment.

Cigarette Smoking and Breast Cancer Risk in Hispanic and Non-Hispanic White Women: The Breast Cancer Health Disparities Study

OBJECTIVE Few epidemiological studies have included Hispanics with the evaluation of the effects of cigarette smoking and breast cancer. We examined the relationship between cigarette smoking, ethnicity, and breast cancer risk using data from the Breast Cancer Health Disparities Study (BCHDS). MATERIALS AND METHODS The BCHDS is a consortium of three population-based case-control studies, including U.S. non-Hispanic whites (NHWs) (1,525 cases; 1,593 controls), U.S. Hispanics/Native Americans (1,265 cases; 1,495 controls), and Mexican women (990 cases; 1,049 controls). Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Breast cancer risk was elevated among Mexican former smokers (OR 1.43, 95% CI 1.04-1.96) and among those who smoked ≥ 31 years (OR 1.95, 95% CI 1.13-3.35), compared to never smokers. In addition, Mexican former smokers with a history of alcohol consumption had increased breast cancer risk (OR 2.30, 95% CI 1.01-5.21). Among NHW premenopausal women, breast cancer risk was increased for smoking ≥ 20 cigarettes per day (OR 1.61, 95% CI 1.07-2.41). CONCLUSION Our findings suggest the possibility of ethnic differences with the associations between cigarette smoking and breast cancer risk.

Associations between prior HPV4 vaccine doses and cervical cancer screening participation.

BACKGROUND Cervical cancer screening, regardless of HPV vaccination, is a cornerstone of cancer prevention. This study evaluated associations between prior HPV vaccine doses and initiation and continued participation of screening by age at vaccination. METHODS Using electronic medical records for a safety net healthcare system (Truman Medical Center), women aged 14-26y vaccinated (n=1123) between 07/01/2006 and 10/1/2009 were randomly selected and matched on birth year and health campus to unvaccinated (n=1123) women. Frequency of screening was determined through 07/01/2013. Hazard ratios (HR) for screening were estimated using Cox proportional hazards regression. RESULTS Screening rates were higher after vaccination: unvaccinated (53%), first (62%), second (59%) or third (61%) doses. Women who initiated screening were less likely to complete the vaccine series, regardless of age. Women receiving one dose were more likely than unvaccinated women to initiate screening (HR=2.98 95% Confidence Interval (CI):2.45-3.61) and were more likely to screen than those receiving two (1 vs. 2, HR=2.94 95% CI:2.09-4.14) or three doses (1 vs. 3, HR=3.15 95% CI:2.21-4.48). Compared to unvaccinated women, women <21y who completed 3-doses were 1.8-times more likely to screen at ≥21y, whereas vaccinated women ≥21y were more likely to screen regardless of number of doses (p<0.0001). CONCLUSIONS Women who were vaccinated were more likely to screen than unvaccinated women; screening rate was highest after and occurred closest to the first vaccine dose. Research evaluating the efficacy of a one-dose vaccine is warranted and may provide both higher vaccination and screening rates.

Abstract A81: Physical activity and survival in long-term Hispanic and non-Hispanic white breast cancer survivors

Introduction: Previous studies have reported that physical activity is associated with improved survival after a breast cancer diagnosis. There are few data, however, for the association of physical activity with survival in Hispanic women. The purpose of this study was to investigate the association of increased physical activity in the year prior to breast cancer diagnosis with all-cause and breast cancer mortality in Hispanic and non-Hispanic white women using data from the New Mexico Women9s Health Study (NMWHS). Study Population and Methods: The NMWHS was a population-based case-control study that included women diagnosed in New Mexico with invasive or in-situ breast cancers in 1992–1994. A total of 722 cases (339 Hispanic and 383 non-Hispanic white) participated in the study. Vital status and specific causes of death were ascertained through December 2008 via linkage with the New Mexico Tumor Registry (NMTR) and the National Death Index (NDI). Usual physical activity was assessed using a standardized questionnaire for the year prior to interview. After excluding women with a previous history of breast cancer or missing covariate data, 641 cases remained for analyses. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox Proportional Hazards models, with time since interview as the underlying time metric, for quartiles of physical activity (MET-h/wk), adjusting for age, breast cancer treatment, menopausal status at time of diagnosis, stage of disease, number of years of supplementary estrogen use, body-mass index (BMI) at time of diagnosis, and energy intake levels in the year preceding diagnosis. Results: During an average 12.0 years of follow-up, 216 deaths were ascertained (123 due to breast cancer). In Hispanic women, compared to 0–25.00 Metabolic Equivalent hours per week (MET-h/wk), the RRs (95% CI) were 0.75(0.42, 1.33) for 25.00–40.15 MET-h/wk, 0.46(0.24, 0.87) for 40.15–62.85 MET-h/wk and 0.41(0.22, 0.76) for >=62.85 MET-h/wk, with a p-trend value of 0.002 for all-cause mortality, and 0.70(0.32, 1.52), 0.47(0.18, 1.19) and 0.42(0.19, 0.93) with a p-trend value of 0.028 for breast cancer mortality. In non-Hispanic white women, the corresponding RRs (95% CI) were 0.60(0.33, 1.10), 1.09(0.63, 1.87) and 0.90(0.51, 1.61) with a p-trend value of 0.763 for all-cause mortality, and 0.65(0.28, 1.53), 0.97(0.44, 2.12) and 0.70(0.31, 1.60) with a p-trend value of 0.609 for breast cancer mortality. Stratified analysis suggests an added benefit for Hispanic women with BMI>=25 when their MET-hr/wk exceeds the median. The RR (95% CI) is 0.44(0.25, 0.78). The same benefit is not seen with non-Hispanic white women or in Hispanic women with BMI These results suggest that the effects of physical activity level prior to breast cancer diagnosis decrease the risk of all-cause and breast-cancer mortality in Hispanic women but not non-Hispanic women. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A81.

Liver Disease in a Residential Cohort With Elevated Polychlorinated Biphenyl Exposures

Endocrine and metabolism disrupting chemicals (EDCs/MDCs) have been associated with environmental liver diseases including toxicant-associated steatohepatitis (TASH). TASH has previously been characterized by hepatocellular necrosis, disrupted intermediary metabolism, and liver inflammation. Polychlorinated biphenyls (PCBs) are environmental EDCs/MDCs associated with the genesis and progression of steatohepatitis in animal models and human liver injury in epidemiology studies. The cross-sectional Anniston Community Health Survey (ACHS) investigates ortho-substituted PCB exposures and health effects near a former PCB manufacturing complex. The rates of obesity, diabetes, and dyslipidemia were previously determined to be high in ACHS. In this study, 738 ACHS participants were categorized by liver disease status using the serum cytokeratin 18 biomarker. Associations between PCB exposures and mechanistic biomarkers of intermediary metabolism, inflammation, and hepatocyte death were determined. The liver disease prevalence was high (60.2%), and 80.7% of these individuals were categorized as having TASH. Sex and race/ethnicity differences were noted. TASH was associated with increased exposures to specific PCB congeners, insulin resistance, dyslipidemia, proinflammatory cytokines, and liver necrosis. These findings are consistent with PCB-related steatohepatitis. ΣPCBs was inversely associated with insulin resistance/production, leptin, and hepatocyte apoptosis, while other adipocytokines were increased. This is possibly the largest environmental liver disease study applying mechanistic biomarkers ever performed and the most comprehensive analysis of PCBs and adipocytokines. It provides insight into the mechanisms of PCB-related endocrine and metabolic disruption in liver disease and diabetes. In the future, associations between additional exposures and liver disease biomarkers will be evaluated in the ACHS and follow-up ACHS-II studies.

Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

The seasonality of abortion in Kentucky

OBJECTIVES Abortion incidence is correlated with seasonal trends in conceptions and births. This retrospective review looks at monthly abortion incidence to detect a seasonal trend. STUDY DESIGN Data on abortion incidence in 2012 were obtained from the Kentucky Department of Vital Statistics. A regression analysis was performed to detect differences in abortion annualized rates by month. RESULTS A total of 3810 abortions analyzed showed a trend in abortion incidence peaking in February and March with 444 and 378 abortions per month, respectively, compared to a mean of 299 in other months (p<.001). This trend persisted for second-trimester abortions with 64 and 56 abortions per month in February and March, respectively, compared to a mean of 30 in other months (p<.001). CONCLUSION The peak in first-trimester abortions correlate with the expected peaks of December conceptions. However, the same trend in second-trimester abortions suggests that women are delaying care.

Abstract C86: Active smoking and breast cancer risk among Hispanic and non-Hispanic white women from the Breast Cancer Health Disparities Study

The association between smoking and breast cancer has been extensively evaluated in epidemiological studies. Some, but not all studies found a positive association between smoking and breast cancer risk, especially among women with long smoking duration. Few studies have included Hispanic women. We evaluated the interaction between active smoking exposure and ethnicity using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies including U.S. non-Hispanic whites (NHW) (1,525 cases; 1,593 controls), U.S. Hispanics/Native Americans (1,265 cases; 1,495 controls), and Mexican women (990 cases; 1,049 controls). Using multivariable logistic regression, odds ratios (ORs) and 95% confidence intervals (CI) were calculated to estimate the risk of breast cancer associated with active smoking exposure and assess differences in associations by ethnicity. We also tested for interaction effects between smoking and ethnicity by menopausal status and by history of alcohol use. Assessment of tobacco usage and active smoking exposures by ethnicity showed that there were significant (p value Citation Format: Avonne E. Connor, Kathy B. Baumgartner, Richard N. Baumgartner, Christina M. Pinkston, Stephanie D. Boone, Esther M. John, Gabriela Torres- Mejia, Lisa M. Hines, Anna R. Giuliano, Roger K. Wolff, Martha L. Slattery. Active smoking and breast cancer risk among Hispanic and non-Hispanic white women from the Breast Cancer Health Disparities Study. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C86. doi:10.1158/1538-7755.DISP13-C86