Citations

Although pathophysiological links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR)-mediated increased mean arterial pressure (MAP) in postmenopause vs. premenopause. Normotensive women in premenopause or postmenopause ( n = 14 and 14; ages: 30 ± 9 and 55 ± 7 yr, respectively; P < 0.01) performed: 1) peak exercise testing and 2) fixed-load cycling at 30% peak workload (48 ± 11 and 38 ± 6 W, respectively; P < 0.01), whereby the initial 3 min were control exercise without RCO (CTL), thereafter including 2 min of bilateral-thigh RCO to 20, 40, 60, 80, or 100 mmHg (randomized), with 2 min deflation between RCO. Both MAP (17 ± 4 vs. 4 ± 4%, P = 0.02) and SVR (16 ± 8 vs. −3 ± 8%, P = 0.04) increased at 80 mmHg from CTL in postmenopause vs. premenopause, respectively. However, cardiac index was similar in postmenopause vs. premenopause at 80 mmHg from CTL (1 ± 6 vs. 7 ± 6%, respectively; P = 0.15). There was no continuous effect of aging in MAP ( P = 0.12), SVR ( P = 0.07), or cardiac index ( P = 0.18) models. These data suggest transient locomotor subsystolic RCO sensitizes musculoskeletal afferents, which provoke increased SVR to generate augmented MAP during exercise in postmenopause. These observations provide a novel approach for understanding the age-independent variability in exercise blood pressure control across the normotensive adult pre- to postmenopause spectrum.

Abstract Van Iterson, EH, Fitzgerald, JS, Dietz, CC, Snyder, EM, and Peterson, BJ. Reliability of triaxial accelerometry for measuring load in men's collegiate ice hockey. J Strength Cond Res 31(5): 1305–1312, 2017—Wearable microsensor technology incorporating triaxial accelerometry is used to quantify an index of mechanical stress associated with sport-specific movements termed PlayerLoad. The test-retest reliability of PlayerLoad in the environmental setting of ice hockey is unknown. The primary aim of this study was to quantify the test-retest reliability of PlayerLoad in ice hockey players during performance of tasks simulating game conditions. Division I collegiate male ice hockey players ( N = 8) wore Catapult Optimeye S5 monitors during repeat performance of 9 ice hockey tasks simulating game conditions. Ordered ice hockey tasks during repeated bouts included acceleration (forward or backward), 60% top-speed, top-speed (forward or backward), repeated shift circuit, ice coasting, slap shot, and bench sitting. Coefficient of variation (CV), intraclass correlation coefficient (ICC), and minimum difference (MD) were used to assess PlayerLoad reliability. Test-retest CVs and ICCs of PlayerLoad were as follows: 8.6% and 0.54 for forward acceleration, 13.8% and 0.78 for backward acceleration, 2.2% and 0.96 for 60% top-speed, 7.5% and 0.79 for forward top-speed, 2.8% and 0.96 for backward top-speed, 26.6% and 0.95 for repeated shift test, 3.9% and 0.68 for slap shot, 3.7% and 0.98 for coasting, and 4.1% and 0.98 for bench sitting, respectively. Raw differences between bouts were not significant for ice hockey tasks ( p > 0.05). For each task, between-bout raw differences were lower vs. MD: 0.06 vs. 0.35 (forward acceleration), 0.07 vs. 0.36 (backward acceleration), 0.00 vs. 0.06 (60% top-speed), 0.03 vs. 0.20 (forward top-speed), 0.02 vs. 0.09 (backward top-speed), 0.18 vs. 0.64 (repeated shift test), 0.02 vs. 0.10 (slap shot), 0.00 vs. 0.10 (coasting), and 0.01 vs. 0.11 (bench sitting), respectively. These data suggest that PlayerLoad demonstrates moderate-to-large test-retest reliability in the environmental setting of male Division I collegiate ice hockey. Without previously testing reliability, these data are important as PlayerLoad is routinely quantified in male collegiate ice hockey to assess on ice physical activity.

Abstract Background: Associations of medical history, lifestyle, and family history of hematological disorders with risk of chronic lymphocytic leukemia (CLL) have been previously established (1), but these exposures have not been well-studied as contributing factors to CLL prognosis. Here we investigate the association of these exposures with time to first treatment (TTFT) in 730 CLL patients. Methods: Newly diagnosed CLL patients seen at the Mayo Clinic between 2002 and 2012 were enrolled. CLL was defined according to the 1996 NCI-Working Group criteria (2). Risk factor data (including body mass index, smoking, alcohol use, sun exposure, having lived on a farm, any allergy, asthma, eczema, blood transfusion, diabetes, rheumatoid arthritis, and family history of hematological malignancy) were collected from self-administered questionnaires. Clinical and prognostic characteristics for CLL were extracted from medical records. Analyses were performed using Cox regression with first treatment as the event. Hazard ratios (HR) and 95% confidence intervals were estimated. We used Bonferroni correction for multiple testing with statistical significance at 0.004. Results: The median age at CLL diagnosis was 63 years (range 36 - 89); 65% were male, and 95% had a Rai stage&lt; III. The median follow up time was 6.3 years, and 40% received treatment. In unadjusted analyses, patients with any history of allergies had significantly longer TTFT (HR = 0.66, 95% CI: 0.51-0.85, P = 0.001). We also observed borderline significance with history of asthma (HR = 0.53, 95% CI: 0.34-0.85, P = 0.008). These associations held after adjusting for important prognostic factors including age, sex, Rai stage, and IGVH mutational status. The other risk factors had non-significant associations (P&gt;0.1). Conclusions: We observed an improved CLL prognosis in patients with a history of any allergies or asthma. These results were independent of other prognostic markers and suggest that an overactive IgE level from environmental exposures may provide insight into the progression of CLL. Literature Cited 1. Slager SL, Benavente Y, Blair A, Vermeulen R, Cerhan JR, Costantini AS, et al. Medical history, lifestyle, family history, and occupational risk factors for chronic lymphocytic leukemia/small lymphocytic lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014 Aug;2014(48):41-51. 2. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996 Jun 15;87(12):4990-7. Citation Format: Sara Beiggi, James M. Foran, O’Byrne Megan, Celine M. Vachon, Timothy G. Call, Neil E. Kay, Tait D. Shanafelt, James R. Cerhan, Susan L. Slager. Medical history, lifestyle, and family history exposures and chronic lymphocytic leukemia outcome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3453.

Abstract Previous studies have shown an increased risk of colorectal cancer (CRC) among moderate to heavy alcohol consumers relative to non-drinkers; however, the relationship between alcohol and CRC survival remains unclear. Using data from the international Colon Cancer Family Registry (CCFR), we assessed the association between pre-diagnostic alcohol intake and survival outcomes after CRC diagnosis, overall and stratified by patient and tumor attributes. CRC cases were identified via population-based cancer registries at four CCFR study sites, with diagnoses of incident, invasive CRC from 1997 to 2006. Study participants completed a risk factor questionnaire at enrollment which included information on several pre-diagnostic behaviors, including consumption of wine, beer, and liquor. Prospective follow-up for survival outcomes was conducted for 4858 CRC cases with complete data on alcohol consumption. Using Cox proportional hazards regression models with delayed entry to account for the time between diagnosis and study enrollment, we compared non-drinkers (i.e., alcohol intake &lt;1 drink per week) to individuals who consumed, on average, &lt;1 serving of alcohol per day (but ≥1 per week), and those who consumed ≥1 serving per day in the years preceding CRC diagnosis. Separate analyses were carried out for overall and disease-specific survival. All models were adjusted for age at diagnosis, sex, study site, year of diagnosis, smoking history, CRC screening history, and body mass index. Over a mean follow-up of 7.5 years, 1872 (39%) study participants died, 1110 (59%) of whom died from CRC. Pre-diagnostic beer and liquor consumption were not associated with CRC survival; however, consumption of ≥1 serving of wine per day was modestly associated with more favorable overall [hazard ratio (HR) = 0.80, 95% confidence interval (CI): 0.63-1.00] and disease-specific survival (HR = 0.83, 95% CI: 0.62-1.12). In stratified analyses, having consumed ≥1 serving of wine per day was slightly, but not statistically significantly, more strongly associated with overall survival among men than among women (HR = 0.71 vs. 0.91, respectively, p-heterogeneity = 0.12) and among those aged ≤50 than those aged &gt;50 years (HR = 0.66 vs. 0.84, p-heterogeneity = 0.35). Similar patterns were noted with respect to disease-specific survival. There were no differences in the relationships between wine consumption and survival outcomes stratified by tumor site, microsatellite instability, BRAF-mutation, or CpG island methylator phenotype status. These results suggest that wine consumption prior to CRC diagnosis is modestly associated with more favorable survival after CRC diagnosis. This modest inverse association does not appear to be limited to specific colorectal tumor subtypes and extends beyond overall survival to disease-specific outcomes. Citation Format: Amanda I. Phipps, Jamaica Robinson, Peter T. Campbell, Aung Ko Win, Jane Figueiredo, Noralane M. Lindor, Polly A. Newcomb. Prediagnostic alcohol consumption and colorectal cancer survival: the Colon Cancer Family Registry. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3425.

Background/aims: Some of the most promising avenues of cancer clinical investigation center on immunotherapeutic approaches. These approaches have provided notable gains in cancer therapeutics with recent Food and Drug Administration approvals of agents of this class in several types of cancers, although gains for ovarian cancer lag behind. This study examined perceptions of therapeutic trials including immunotherapy and virotherapy among ovarian cancer patients and their family members. Methods: A total of 72 semi-structured qualitative interviews were conducted with 33 patients and 39 family members at two National Cancer Institute–designated comprehensive cancer centers. Eligible patients were diagnosed with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma and had experience with clinical trial conversations; family members were nominated by patients and interviewed separately. Applied thematic analysis was used to understand and interpret the data. Results: More participants were aware of vaccine trials than virus trials, although more than half had heard of at least one of them. Initial reactions to vaccine trials were generally favorable. For many, childhood experience with vaccines lent a familiar frame of reference. Virus trials elicited more negative initial reactions, including the use of adjectives such as “scary” and “dreadful.” Viruses seemed contagious or difficult to control. Increased receptivity to these trials occurred in the context of limited therapeutic options and cancer recurrence. Most participants, including those not immediately drawn to these types of trials, indicated openness to learning more. Conclusion: Although vaccine and viral trials are both immunologically based therapeutic approaches, patients who are offered these trials may perceive their potential benefit and safety quite differently. There is a need to consider terminology, solicit and address “gut reactions,” and provide information that enables patients and their family members to better understand the science behind these trials.

Lack of treatment fidelity can be an important source of variation affecting the credibility and utility of outcomes from behavioral intervention research. Development and implementation of a well-designed treatment fidelity plan, especially with research involving underserved populations, requires careful conceptualization of study needs in conjunction with what is feasible in the population. The purpose of this article is to review a fidelity-monitoring plan consistent with the National Institutes of Health Behavior Change Consortium guidelines (e.g., design, training, delivery, receipt, and enactment) for an intervention trial designed to improve physical activity and nutrition among immigrant and refugee families. Description of the fidelity monitoring plan is provided and challenges related to monitoring treatment fidelity in a community-based participatory intervention for immigrant and refugee families are discussed.

AbstractBackground and AimTumor testing of colorectal cancers (CRC) for mismatch repair (MMR) deficiency is an effective approach to identify carriers of germline MMR gene mutation (Lynch syndrome). The aim of this study was to identify MMR gene mutation carriers in two cohorts of population‐based CRC utilizing a combination of tumor and germline testing approaches.MethodsColorectal cancers from 813 patients diagnosed with CRC < 60 years of age from the Australasian Colorectal Cancer Family Registry (ACCFR) and from 826 patients from the Melbourne Collaborative Cohort Study (MCCS) were tested for MMR protein expression using immunohistochemistry, microsatellite instability (MSI), BRAFV600E somatic mutation, and for MLH1 methylation. MMR gene mutation testing (Sanger sequencing and Multiplex Ligation Dependent Probe Amplification) was performed on germline DNA of patients with MMR‐deficient tumors and a subset of MMR‐proficient CRCs.ResultsOf the 813 ACCFR probands, 90 probands demonstrated tumor MMR deficiency (11.1%), and 42 had a MMR gene germline mutation (5.2%). For the MCCS, MMR deficiency was identified in the tumors of 103 probands (12.5%) and seven had a germline mutation (0.8%). All the mutation carriers were diagnosed prior to 70 years of age. Probands with a MMR‐deficient CRC without MLH1 methylation and a gene mutation were considered Lynch‐like and comprised 41.1% and 25.2% of the MMR‐deficient CRCs for the ACCFR and MCCS, respectively.ConclusionsIdentification of MMR gene mutation carriers in Australian CRC‐affected patients is optimized by immunohistochemistry screening of CRC diagnosed before 70 years of age. A significant proportion of MMR‐deficient CRCs will have unknown etiology (Lynch‐like) proving problematic for clinical management.