Citations

Background. Preterm Premature Rupture of Membranes (PPROM) is a major leading cause of preterm births. While the cause for PPROM remains unidentified, it is anticipated to be due to subclinical infection, since a large proportion of PPROM patients display signs of chorioamnionitis. Since subclinical infections can be facilitated by dysbiosis, our goal was to characterize the vaginal microbiome and amniotic fluid discharge upon PPROM, through latency antibiotic treatment, and until delivery, to detect the presence of pathogens, microbiota alteration, and microbial response to treatment. Methods. Enrolled subjects (15) underwent routine institutional antenatal care for PPROM, including the administration of latency antibiotics. Serial vaginal swabs were obtained from diagnosis of PPROM through delivery and the sequencing of the V3–V5 region of the 16S rRNA gene was performed for all collected samples. Results. The results show that Lactobacilli species were markedly decreased when compared to vaginal swabs collected from uncomplicated pregnancy subjects with a matched gestational time. Prevotella and Peptoniphilus were the most prevalent taxa in PPROM subjects at presentation. The vaginal microbiome of the PPROM subjects varied substantially intra- and inter-subjects. Several taxa were found to be significantly reduced during and after the antibiotic treatment: Weeksella , Lachnospira , Achromobacter , and Pediococcus . In contrast, Peptostreptococcus and Tissierellaceae ph2 displayed a significant increase after the antibiotic treatment. However, the relative abundance of Lactobacillus , Prevotella , and Peptoniphilus was not substantially impacted during the hospitalization of the PPROM subjects. The deficiency of Lactobacillus , and constancy of known pathogenic species, such as Prevotella and Peptoniphilus during and after antibiotics, highlights the persistent dysbiosis and warrants further investigation into mitigating approaches. Discussion. PPROM is responsible for one third of all preterm births. It is thought that subclinical infection is a crucial factor in the pathophysiology of PPROM because 25–40% of patients present signs of chorioamnionitis on amniocentesis. Here we sought to directly assess the bacterial content of the vagina and leaking amniotic fluid of subjects at presentation, throughout treatment and up until delivery, in order to search for common pathogens, microbiota changes, and microbial response to latency antibiotic treatment. We have found that the vaginal microbiome of PPROM subjects is highly variable and displays significant changes to treatment. However, the unchanging deficiency of Lactobacillus , and persistence of known pathogenic species, such as Prevotella and Peptoniphilus from presentation, through antibiotic treatment and up until delivery, highlights the persistent dysbiosis and warrants further investigation into mitigating approaches.

Objectives To determine event‐free survival after transcatheter closure of ventricular septal defect (VSD), and to identify predictors of adverse events (AE) in post myocardial infarction VSD (post‐MI VSD) subgroup. Background There are limited data on mid‐term follow‐up after transcatheter VSD closure. Methods Retrospective review of 27 cases of transcatheter VSD closure (post‐MI = 18 and non‐ischemic = 9) performed from 1999 to 2013. We defined AE as death, device embolization, hemolysis requiring blood transfusion, heart block and reintervention. Results In the post‐MI VSD subgroup, mean age and follow‐up was 69 ± 11 and 7.3 ± 7 years, respectively. AE occurred in 8 (44%) patients (death‐3, device embolization‐1, hemolysis‐1, surgical VSD closure‐2, reintervention‐1). Event‐free survival was 56% at 1 month and 5 years, and all AE occurred in the periprocedural period. Cardiogenic shock (HR: 3.21, CI: 1.82–5.41, P = 0.002), and VSD closure in acute phase (HR: 2.14, CI: 1.12–4.31, P = 0.004) were independent predictors of AE. In the non‐ischemic VSD subgroup, mean age and follow‐up was 49 ± 15 and 8.7 ± 8 years, respectively. AE occurred in 3 (33%) patients (late death‐1, surgical VSD closure‐2). For the entire cohort, freedom from death was 89% and 85% at 1 month and 5 years, and event‐free survival was 70% and 61% at 1 month and 5 years. Conclusions Transcatheter closure of post‐MI VSD carries a moderate risk of periprocedural complications but low event rates afterwards. By comparison, device closure of non‐ischemic VSD has lower periprocedural morbidity but some patients continued to experience AE during follow‐up. © 2015 Wiley Periodicals, Inc.

ObjectiveTo describe the effects of percutaneously implanted valve‐in‐valve in the tricuspid position for patients with pre‐existing transvalvular device leads.MethodsIn this case series, we describe implantation of the Melody valve and SAPIEN XT valve within dysfunctional bioprosthetic tricuspid valves in three patients with transvalvular device leads.ResultsIn all cases, the valve was successfully deployed and device lead function remained unchanged. In 1/3 cases with 6‐month follow‐up, device lead parameters remain unchanged and transcatheter valve‐in‐valve function remains satisfactory.ConclusionsTranscatheter tricuspid valve‐in‐valve is feasible in patients with pre‐existing transvalvular devices leads. Further study is required to determine the long‐term clinical implications of this treatment approach. © 2015 Wiley Periodicals, Inc.

Abstract Background: Statins are the most widely prescribed cholesterol-lowering drugs in the United States, with approximately 25% of US adults using statins by 2008. The anti-carcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to ‘stage migration’ with statin users more likely diagnosed with early rather than late stage cancer. We evaluated the effects of statins on breast cancer stage migration and breast cancer-specific mortality in the Women’s Health Initiative (WHI) Clinical Trial and Observational Study. Methods: The study population included 128,675 postmenopausal women aged 50 to 79 years, with 7,883 newly-diagnosed pathologically-confirmed cases of in situ (19%), local stage (61%), regional stage (19%) and distant stage (1%) breast cancer and 401 deaths due to breast cancer after an average of 11.5 (SD=3.7) years of follow-up. To reduce the possibility of detection bias, we excluded women who did not report a mammogram within 5 years of study entry, and who had no health insurance or medical care provider (n=28,237). Stage was coded using criteria implemented in the Surveillance, Epidemiology and End Results Program and stratified into early stage (in situ and local) vs. late stage (regional and distant). Information on statin use prior to breast cancer diagnosis was collected at baseline and years one, three, six, and nine years post-baseline. Self- and interviewer-administered questionnaires were used to collect risk factor information. Cause of death was based on medical record review by physician adjudicators. Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) to evaluate the relationship between statin use as a time-dependent exposure and diagnosis of late stage breast cancer and breast cancer-specific mortality adjusting for important confounders. For these models, participants who had early stage breast cancer or who died during follow-up were censored at time of diagnosis or death, respectively. We also evaluated the effect of statins stratified by estrogen receptor (ER) status. Statistical tests were two-sided. Results: Statins were used by 10,474 women (8%) at baseline. In the multivariable-adjusted time-dependent model, statin use was associated with a marginal reduction in risk of late stage breast cancer (HR 0.84, 95% CI: 0.70-1.02, p=0.082) and a reduction in risk of late stage estrogen receptor positive breast cancer (HR 0.79, 95% CI: 0.63-0.99, p=0.044). Statin use was also associated with a marginal reduction in breast cancer-specific mortality although it did not reach statistical significance (HR 0.59, 95% CI: 0.32-1.06, p=0.075). Conclusions: In the WHI, statin use was associated with a modest reduction in risk of late stage estrogen positive breast cancer and a non-significant decrease in breast cancer mortality. We are currently performing sensitivity analyses on these models. Studies using other large data sets with longer follow-up and information on cancer-directed therapy are needed to further evaluate this possible association. Citation Format: Monica P Arun, Pinkal Desai, Amy Lehman, Marilyn L Kwan, JoAnn E Manson, Sayeh Lavasani, Sylvia Wasswertheil-Smoller, Gloria E Sarto, Meryl S LeBoff, Jane Cauley, Michele L Cote, Jennifer Beebe-Dimmer, Allison Jay, Rowan T Chlebowski, Michael S Simon. Statins and breast cancer stage and mortality in the Women's Health Initiative cohort [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-04.

Background: A women-based formula for calculation of age-predicted maximum heart rate [age-predicted maximum heart rate=206−(0.88×age)] was established in asymptomatic volunteer women undergoing treadmill exercise tolerance testing (ETT). We sought to perform a comparison of the performance of this women-based formula for prediction of peak heart rate to the traditional formula [220−age] and our own database-generated prediction formula in a large database of women undergoing ETT. Methods: We performed a retrospective analysis of all consecutive women who underwent symptom-limited Bruce protocol ETT at the Mayo Clinic from 1994 to 2010. Women with known cardiovascular disease or those using beta blockers, calcium channel blockers, or digitalis were excluded. Separate analyses were performed according to symptomatic status. Results: The study included 11,029 women (89.4% Caucasian) with a mean age 52±12 years; 3,632 (33%) were referred specifically for evaluation of symptoms. Age-predicted maximum heart rate calculated by the traditional formula was achieved by 49.7% of women versus 69.9% by the women-based formula with most of the underestimation observed in older women. Average absolute deviation between achieved and predicted peak heart rate (HR) was 10.85±9.18 bpm for traditional versus 11.98±9.00 for women-based formulas (dependent t =−16.64, p <0.0001). The linear regression line calculated from our population [HR=201−(0.67×age)] was closer to the women-based formula, both in terms of intercept and slope than the traditional formula. Peak HR was shown to be slightly affected (−2.5 bpm) by symptom status at referral, whereas smoking and diabetes more significantly reduced achieved peak HR. Conclusions: The women-based formula underestimated peak HR, especially in older women, but was observed to be closer in both intercept and slope to the regression line determined from our study in this large population of female patients. These sex-unique observations should be taken into account when determining adequacy and targets for ETT in women.