Citations

BackgroundTranscatheter aortic valve replacement (TAVR) with the balloon‐expandable Sapien transcatheter heart valve improves survival compared to standard therapy in patients with severe aortic stenosis (AS) and is noninferior to surgical aortic valve replacement (AVR) in patients at high operative risk. Nonetheless, a significant proportion of patients may require pre‐emptive or emergent support with cardiopulmonary bypass (CPB) and/or intra‐aortic balloon pump (IABP) during TAVR due to pre‐existing comorbid conditions or as a result of procedural complications. Objectives: We hypothesized that patients who required CPB or IABP would have increased periprocedural complications and reduced long‐term survival. In addition, we sought to determine whether preprocedural variables could predict the need for CPB and IABP. Methods: The study population included 2,525 patients in the PARTNER Trial (Cohort A and B) and the continuing access registry (CAR). Patients that received CPB or IABP were compared to patients that did not receive either, and then further divided into those that received support pre‐TAVR and those that were placed on support emergently. Results: One‐hundred sixty‐three patients (6.5%) were placed on CPB and/or IABP. The use of CPB or IABP was associated with higher 1 year mortality (49.1% vs. 21.6%, P < 0.001). In multivariable analysis, utilization of CPB or IABP was an independent predictor of 30 day (HR 6.95) and 1‐year (HR 2.56) mortality. Although mortality was highest in emergent cases, mortality was also greater in planned CPB and IABP cases compared with non‐CPB/IABP cases (53.3% and 40.3% vs. 21.6%, P < 0.001). Conclusions: These findings indicate that CPB and IABP use in TAVR portends a poor prognosis and its utilization, particularly in the setting of pre‐emptive use, needs reconsideration. © 2015 Wiley Periodicals, Inc.

Nitrate and nitrite are precursors in the endogenous formation of N‐nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow‐up survey. Nitrate‐nitrogen (NO3‐N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were computed based on each woman's duration at the residence. We computed multivariable‐adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression. We tested interactions of nitrate with TTHMs and dietary factors known to influence NOC formation. Ovarian cancer risk was 2.03 times higher (CI = 1.22–3.38, ptrend = 0.003) in the highest quartile (≥2.98 mg/L) compared with the lowest quartile (≤0.47 mg/L; reference) of NO3‐N in public water, regardless of TTHM levels. Risk among private well users was also elevated (HR = 1.53, CI = 0.93–2.54) compared with the same reference group. Associations were stronger when vitamin C intake was <median (pinteraction = 0.01 and 0.33 for private well and public supplies, respectively). Dietary nitrate was inversely associated with ovarian cancer risk (ptrend = 0.02); whereas, dietary nitrite from processed meats was positively associated with the risk (ptrend = 0.04). Our findings indicate that high nitrate levels in public drinking water and private well use may increase ovarian cancer risk among postmenopausal women.

AbstractSeveral lines of evidence from Alzheimer's disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging—Alzheimer's Association revised criteria for AD provided a framework for this new thinking. As a result of this growing understanding, several research efforts have launched or will be launching large secondary prevention trials in AD. These and other efforts have clearly demonstrated a need for better measures of cognitive and functional change in people with the earliest changes associated with AD. Recent draft guidance from the US Food and Drug Administration further elevated the importance of cognitive and functional assessments in early stage clinical trials by proposing that even in the pre‐symptomatic stages of the disease, approval will be contingent on demonstrating clinical meaningfulness. The Alzheimer's Association's Research Roundtable addressed these issues at its fall meeting October 28–29, 2013, in Washington, D.C. The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD.

Abstract Background: Hormone therapy (HT) may prevent colorectal cancer (CRC), but the molecular mechanisms have not been fully defined. Expression of estrogen receptor beta (ERβ) has been associated with CRC stage and survival and may influence HT-related prevention pathways. In this prospective cohort study, we examined HT-associated CRC risk by ERβ protein expression levels in the population-based Iowa Women's Health Study (IWHS). Methods: The IWHS recruited 41,836 randomly selected Iowa women, ages 55-69 years, with a valid driver's license at study entry (1986). Exposure variables were assessed at baseline, by self-report. Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected from 732 CRC cases, diagnosed through 12/31/2002, for molecular epidemiology studies. HT was categorized as never, former, and current and with durations of &lt;=5 years or &gt;5 years. ERβ protein expression was determined by immunohistochemistry on tissue microarrays. For each tumor core, both staining intensity (0-3) and proportion of cells stained (0-5) were scored. These two scores were added to determine negative (0), low (1-5) or high (6-8) ERβ protein expression levels. Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: Complete HT and ERβ data were available from 484 CRC cases. Associations between HT and CRC subtypes defined by ERβ expression level are shown in the Table. Conclusions: Data from the IWHS cohort suggest that current and longer-duration HT exposure favorably influence the risk for ERβ-neg or ERβ-low CRC cases to a greater degree than ERβ-high CRC cases. Further investigation is required to confirm these observations, and to clarify the underlying mechanisms. ERβ Neg or Low ERβ High Hormone Therapy Person years Events, N RR* (95% CI) Events, N RR* (95% CI) Never 341377 128 1.00 (Ref.) 196 1.00 (Ref.) Ever 212696 62 0.74 (0.54,1.03) 98 0.82 (0.63,1.07) Former 151535 48 0.79 (0.56,1.12) 67 0.73 (0.54,0.99) Current 61161 14 0.60 (0.33,1.09) 31 1.11 (0.74,1.64) P-trend 0.05 0.52 Duration &lt; = 5yrs 148704 47 0.84 (0.59,1.19) 68 0.80 (0.60,1.08) &gt;5yrs 60064 14 0.5 (0.26,0.93) 28 0.89 (0.59,1.34) P-trend 0.03 0.25 Citation Format: Lori S. Tillmans, Robert A. Vierkant, Alice H. Wang, Charles F. Lynch, Kristin E. Anderson, Amy J. French, Robert W. Haile, John D. Potter, Susan L. Slager, Thomas C. Smyrk, Stephen N. Thibodeau, James R. Cerhan, Paul J. Limburg. Hormone therapy and incident colorectal cancer risk by ER beta protein expression level in a population-based cohort of older women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3652. doi:10.1158/1538-7445.AM2013-3652

Abstract Background: Nitrate and nitrite are precursors of N-nitroso compounds, known animal and human carcinogens. Nitrate and nitrite are common in foods, such as vegetables and processed meats, and nitrate is a contaminant of drinking water. We previously reported an increased ovarian cancer risk associated with higher nitrate intake in public water supplies in the Iowa Women's Health Study. Here, we report results based on an additional 12 years of follow-up and we present results for dietary nitrate and nitrite intake. Methods: Among 28,555 postmenopausal women aged 55–69 y at baseline, we identified 315 incident epithelial ovarian cancers between 1986 and 2010. Dietary nitrate and nitrite intakes were assessed using a food frequency questionnaire at baseline. Information on drinking water source was obtained in 1989. Nitrate-nitrogen (NO3-N) levels in public water supplies (average level 1955-1988) and water sources (finished surface or ground water) were from a database of monitoring data for Iowa water utilities. Cox proportional hazards regression generated hazard ratios (HR) and 95% confidence intervals (CI). Because disinfection by-products (DBP) are higher in surface water and have been associated with increased risk for certain cancers, we determined whether the association between nitrate intake from drinking water and ovarian cancer risk differed by water source. Results: Neither total dietary nitrate nor nitrite intake was associated with ovarian cancer risk after adjusting for age, energy intake, family history of ovarian cancer, number of live births, and history of unilateral oophorectomy. Nitrate and nitrite intakes from animal or plant sources, or processed meats were not associated with ovarian cancer risk. Among women who drank public water, we observed an increased risk for ovarian cancer with higher average levels of NO3-N (ptrend=0.004). Compared with women in the lowest quartile of NO3-N levels (&lt;0.36 mg/L), risk was 1.81 (95% CI=1.08-3.05) and 2.02 (95% CI=1.21-3.36) times higher in the third (1.0-2.5 mg/L) and fourth (&gt;2.5 mg/L) quartiles, respectively. Ovarian cancer risk among private well water drinkers was elevated (HR=1.52, 95% CI=0.91-2.53) but not statistically significantly different from the referent group. When stratified by water source, the positive association between NO3-N levels in public water and ovarian cancer risk was confined to women who drank water from surface sources (ptrend=0.007; pinteraction=0.04). Conclusions: Dietary nitrate or nitrite intake was not associated with ovarian cancer risk. Our findings for nitrate intake from public water supplies suggest that nitrate intake from drinking water may increase ovarian cancer risk, particularly in the likely presence of other contaminants found in surface water. Further evaluation of DBP and other water contaminant levels on ovarian cancer risk in this population is warranted. Citation Format: Maki Inoue-Choi, Kristin E. Anderson, James R. Cerhan, Peter J. Weyer, Mary H. Ward. Dietary intake of nitrate and nitrite, nitrate in drinking water, and ovarian cancer risk among postmenopausal women in Iowa. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 149. doi:10.1158/1538-7445.AM2013-149

Shoulder pain and pathology are common in manual wheelchair (MWC) users with paraplegia, and the biomechanical mechanism of injury is largely unknown. Establishing patterns of MRI characteristics in MWC users would help advance understanding of the mechanical etiology of rotator cuff disease, thus improving the logic for prescribed interventions. The purpose of this study was to report detailed shoulder MRI findings in a sample of 10 MWC users with anterolateral shoulder pain. The imaging assessments were performed using our standardized MRI Assessment of the Shoulder (MAS) guide. The tendon most commonly torn was the supraspinatus at the insertion site in the anterior portion in either the intrasubstance or articular region. Additionally, widespread tendinopathy, CA ligament thickening, subacromial bursitis, labral tears, and AC joint degenerative arthrosis and edema were common. Further reporting of detailed shoulder imaging findings is needed to confirm patterns of tears in MWC users regarding probable tendon tear zone, region, and portion. This investigation was a small sample observational study and did not yield data that can define patterns of pathology. However, synthesis of detailed findings from multiple studies could define patterns of pathological MRI findings allowing for associations of imaging findings to risk factors including specific activities.

Abstract Background: Allergic diseases signify immune dysregulation attributable to underlying genetics and environmental exposures. Associations between various allergies and hematopoietic cancers have been observed, albeit inconsistently; however, few prospective studies have examined the risk, and even fewer among older adults. Methods: We examined risk of incident hematopoietic cancers in those reporting allergic diseases in a population-based cohort of 22,601 older women (Iowa Women's Health Study). Self-reported allergic status, including asthma, hay fever, eczema, and/or other allergies, was determined via questionnaire in 1997 (mean age, 72 years; range, 63–81 years). Incident cancers were ascertained by linkage with the Iowa Cancer Registry from 1997 to 2011. Cox proportional hazards regression was performed to estimate multivariate-adjusted HR and 95% confidence intervals (CI) for myeloid (N = 177) and lymphoid (N = 437) malignancies, respectively. Results: Allergic diseases were not associated with risk of myeloid (HR, 1.00; 95% CI, 0.72–1.37) or lymphoid (HR, 0.99; 95% CI, 0.81–1.22) malignancies overall, or for most allergic and malignant subtypes examined. Self-reported asthma was positively associated with development of myelodysplastic syndrome (MDS; HR, 2.00; 95% CI, 0.93–4.32). In addition, there was a 30% to 40% decrease in risk of both lymphoid and myeloid cancers in those reporting rural residences but no association in those reporting urban residences; the interaction between residence and allergy was statistically significant for lymphoid malignancies (Pinteraction = 0.05). Conclusions and Impact: These results suggest that asthma may contribute to the pathogenesis of MDS, a finding consistent with the chronic antigen stimulation hypothesis. Susceptibility differences by location of residence are concordant with the hygiene hypothesis and merit additional exploration. Cancer Epidemiol Biomarkers Prev; 23(9); 1903–12. ©2014 AACR.