AimsContemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation.Methods and resultsIn a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed.ConclusionIn patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function.

PurposeTo assess the clinical utility of a recently developed highly sensitive cardiac troponin T (hs-cTnT) assay for providing prognostic information on patients with sepsis.MethodscTnT levels were measured by the novel hs-cTnT assay at two time points (inclusion and 72 h thereafter) in a subgroup of patients from the FINNSEPSIS study and associations with clinical outcomes were examined. Results for the hs-cTnT assay were compared to those of the established fourth-generation cTnT assay.ResultscTnT measured by the fourth-generation and hs-cTnT assay was detectable in 124 (60%) and 207 (100%) patients, respectively, on inclusion in this study. hs-cTnT levels on inclusion correlated with several indices of risk in sepsis, including the simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores. The level of hs-cTnT on inclusion was higher in hospital non-survivors (n = 47) than survivors (n = 160) (median 0.054 [Q1–3, 0.022–0.227] versus 0.035 [0.015–0.111] μg/L, P = 0.047), but hs-cTnT level was not an independent predictor of in-hospital mortality. hs-cTnT levels on inclusion were also higher in patients with septic shock during the hospitalization (0.044 [0.024–0.171] versus 0.033 [0.012–0.103] μg/L, P = 0.03), while this was not the case for the fourth-generation cTnT assay or NT-proBNP levels.ConclusionsCirculating hs-cTnT is present in patients with severe sepsis and septic shock, associates with disease severity and survival, but does not add to SAPS II score for prediction of mortality. hs-cTnT measurement could still have a role in sepsis as an early marker of shock.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-010-2051-x) contains supplementary material, which is available to authorized users.

Background/Aims: A food frequency questionnaire (FFQ) and a database for dietary supplements were developed for use in the Norwegian Mother and Child Cohort Study (MoBa). The aim of the present study was to investigate the relation between reported use and biomarkers in supplement and nonsupplement users and to validate self-reported intake of dietary supplements in mid pregnancy. Method: 120 women were recruited from MoBa, and 119 subjects completed the MoBa FFQ and a 4-day weighed food diary. Information on supplement use was collected by both methods. Venous blood specimens and 24-hour urine samples were obtained for measurement of dietary biomarkers. Results: Biomarker concentration/excretion and intake differed significantly between supplement and nonsupplement users for vitamin D, carotenoids, folate, the n–6/n–3 fatty acid ratio and iodine (p < 0.05 for all variables). Flavonoid excretion was higher in flavonoid-supplement users (p < 0.05). Significant correlations between total dietary intake (food and supplements) and biomarker concentration/excretion were found for vitamin D (r = 0.45, p < 0.001), folate (r = 0.26, p = 0.005), the n–6/n–3 fatty acid ratio (r = 0.36, p < 0.001) and iodine (r = 0.42, p < 0.001). Conclusion: The biochemical indicators examined in this study confirmed differences in self-reported micronutrient intake between supplement and nonsupplement users for vitamin D, beta-carotene, folate, n–3 fatty acids, flavonoids and iodine.

Objective: Few biomarkers for dietary intake of various food groups have been established. The aim of the present study was to explore whether selenium (Se), iodine, mercury (Hg) or arsenic may serve as a biomarker for total fish and seafood intake in addition to the traditionally used n-3 fatty acids EPA and DHA. Design: Intake of fish and seafood estimated by an FFQ was compared with intake assessed by a 4 d weighed food diary and with biomarkers in blood and urine. Setting: Validation study in the Norwegian Mother and Child Cohort Study (MoBa). Subjects: One hundred and nineteen women. Results: Total fish/seafood intake (median 39 g/d) calculated with the MoBa FFQ was comparable to intake calculated by the food diary (median 30 g/d, r S 5 0?37, P , 0?001). Erythrocyte DHA and blood Hg, Se and arsenic concentrations were positively correlated with intake of fish and seafood, but the association for DHA was weakened by the widespread use of supplements. The main finding was the consistent positive association between the intake of fish/seafood and blood arsenic concentration. In multivariate analyses, blood arsenic was associated with blood Hg and fish and seafood intake. In these models, arsenic turned out to be the best indicator of intake of fish and seafood, both totally and in subgroups of fish/seafood intake. Conclusions: While DHA reflected the intake of fatty fish and n-3 PUFA supplements, blood arsenic concentration also reflected the intake of lean fish and seafood. Blood arsenic appears to be a useful biomarker for total fish and seafood intake. Keywords Biomarkers Fish and seafood intakePregnant women Blood arsenic Erythrocyte DHA Assessing trends in eating habits and dietary patterns is an essential component in the surveillance of population health and the development of dietary advice and interventions. Dietary monitoring requires a tool validated in the target population, and biomarkers of dietary exposure may assist in uncovering the errors associated with the method in use (1) . For a biomarker to be used for validation of a dietary instrument, it should have a strong direct and independent relationship with the nutrient or food group of interest. Recovery biomarkers, like doubly labelled water (2) and urinary N (3) , are less influenced by the body's homeostatic control than concentration biomarkers, which are extensively used in spite of their weaker association with consumption (4) . Biomarkers that reflect the intake of a food group rather than a specific nutrient are scarce. Plasma carotenoids and urinary flavonoids have been used as biomarkers of fruit and vegetable groups (5,6) and plasma or tissue n-3 PUFA, mainly EPA and DHA, have been used as biomarkers of both total fish and fatty fish intake (7,8) . However, as lean or semi-lean fish and seafood comprise nearly two-thirds of the total fish intake in Norway (9) , a biomarker related to total fish/seafood intake rather than fatty fish and fish-oil supplements could contribute to better validation of this food group than EPA o...