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Background: Leukemia incidence has increased in recent decades among European children, -suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M(1)dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M(1)dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX (R) (chemically activated luciferase expression for androgens) (8 genes), ER alpha CALUX (R) (for estrogens) (2 genes), and DR CALUX (R) (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/ 2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.

Little is known about excessive daytime sleepiness (EDS) in heart failure (HF). The aim of this cross-sectional descriptive study was to describe the prevalence of EDS and factors associated with it in HF. A secondary purpose was to explore the correlates of fatigue. We enrolled a consecutive sample of 280 adults with a confirmed diagnosis of chronic HF from three outpatient settings in the northeastern United States. Patients with major depressive illness were excluded. Clinical, sociodemographic, behavioral, and perceptual factors were explored as possible correlates of EDS. Using an Epworth Sleepiness Scale score > 10, the prevalence of EDS was 23.6%. Significant determinants of EDS were worse sleep quality ( p = .048), worse functional class ( p = .004), not taking a diuretic ( p = .005), and lack of physical activity ( p = .04). Only sleep quality was associated with fatigue ( p < .001). Sleep-disordered breathing was not significantly associated with EDS or with fatigue. These factors may be amenable to intervention.

Background: Long-term anticoagulation therapy with warfarin is recommended for LVAD patients. Compared to other warfarin-treated patients, the LVAD population has a higher rate of suboptimal INRs and a lower average time in the therapeutic window. Suboptimal anticoagulation is a major reason for hospital readmission. We describe our experience with the use of half-dose enoxaparin (0.5 mg/kg/dose) bridging therapy, as a potential alternative to hospital readmission for LVAD-patients with subtherapeutic INRs who may be at higher risk of thrombotic events. Methods: LVAD outpatients with sub-therapeutic INRs were selected to receive half therapeutic dose enoxaparin as bridge therapy based on our VAD anticoagulation protocol. Selection criteria included current INR, VAD type and timing of implantation, history of bleeding or thrombotic events, renal function, medication adherence, and ability to effectively administer enoxaparin injections. The general threshold for bridging was an INR ! 1.6. Enoxaparin was dosed as 0.5 mg/kg every 12 hours. Outpatient INR monitoring and follow-up was conducted by the VAD Coordinator and pharmacist. Within 24 hours of initiation of therapy, a pharmacist telephoned the patient to reinforce proper administration technique and to answer medication-specific questions. Additional telephone communications were conducted by the pharmacist and VAD Coordinator to assess for bleeding complications and duration of therapy. Patients are monitored routinely for thrombus at each ambulatory clinic visit. Results: During the initial 6 months of this program, 15 patients (11 HeartMate II, 3 HeartWare LVAD, 1 Heartware BiVad) were treated with half-dose enoxaparin. The mean INR upon initiation of therapy was 1.4 (range 1.2 to 1.7). Patients received an average of 7.2 enoxaparin doses (range 4 to 14) for a mean duration of therapy of 3.5 days (range 2 to 7). In total, 108 doses were administered accounting for 54 patient days of therapy. No patient was admitted to a hospital due to bleeding or thrombotic events. Minor bleeding, described as mild bleeding at the injection site and increased bruising, was reported in 5 patients (30%). During the observation period, 14 patients (93.3%) completed the protocol with achievement of a therapeutic INR; one patient discontinued therapy due to hospital admission not related to anticoagulation management. Conclusion: In this small series, half-dose enoxaparin appears to be a feasible strategy to bridge selected ambulatory VAD patients with sub-therapeutic INRs. Further investigation is needed to determine its safety and efficacy in a larger population of patients