Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been shown to elicit harmful effects on the host, and were recently proposed to promote tumor progression and spread. Here we report significant elevations of plasma H3Cit in patients with advanced cancer compared with age-matched healthy individuals. These elevations were specific to cancer patients as no increase was observed in severely ill and hospitalized patients with a higher non-malignant comorbidity. The analysis of neutrophils from cancer patients showed a higher proportion of neutrophils positive for intracellular H3Cit compared to severely ill patients. Moreover, the presence of plasma H3Cit in cancer patients strongly correlated with neutrophil activation markers neutrophil elastase (NE) and myeloperoxidase (MPO), and the inflammatory cytokines interleukin-6 and -8, known to induce NETosis. In addition, we show that high levels of circulating H3Cit strongly predicted poor clinical outcome in our cohort of cancer patients with a 2-fold increased risk for short-term mortality. Our results also corroborate the association of NE, interleukin-6 and -8 with poor clinical outcome. Taken together, our results are the first to unveil H3Cit as a potential diagnostic and prognostic blood marker associated with an exacerbated inflammatory response in patients with advanced cancer.

Objective To estimate the risk of pulmonary embolism and venous thromboembolism in pregnant women after in vitro fertilisation.Design Cross sectional study. Setting Sweden.Participants 23 498 women who had given birth after in vitro fertilisation between 1990 and 2008 and 116 960 individually matched women with natural pregnancies.Main outcome measures Risk of pulmonary embolism and venous thromboembolism (identified by linkage to the Swedish national patient register) during the whole pregnancy and by trimester.

Rabbits fed a 1% cholesterol diet with or without the antioxidant butylated hydroxytoluene (BHT) developed typical atherosclerotic lesions. The addition of BHTgave higher levels of total cholesterol (+40%), triglycerides (+250%), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) in plasma. Despite the lower plasma lipid levels, the degree of atherosclerosis of the aortic surface was considerably higher in rabbits fed cholesterol than in the group treated with cholesterol and BHT. The mean atherosclerotic involvement was 18.6 ±4.4% in the former group and 5.9±1.7% in the latter group (p=0.02). In all animals, there was a high correlation between the area of the arterial lesion and cholesterol content (r=0.96). Serum levels of cholesterol autooxidation products (7-ketocholesterol and cholesterol 5tt,6«-epoxide) were lower in the group of rabbits treated with BHT (p<0.005). Serum levels of vitamin E were slightly higher in the BHT group. There was no significant difference in the clearance of /3-VLDL between the two treatment groups after using either 0-VLDL from cholesterol-fed animals or /3-VLDL from BHT-fed animals. The results are in accord with the contention that oxidative modification of lipoproteins is important for the development of atherosclerosis and that antioxidants may have a protective effect At present, however, other explanations cannot be completely excluded, for example, effects of antioxidants on immunologic factors or monocyte adhesion. [Arteriosclerosis and Thrombosis 1991;ll:15-22) R esults from several previous studies suggest that oxidative modification of low density lipoprotein (LDL) may enhance its atherogenecity and contribute to development of atherosclerosis.1 Some of the intrinsic changes in LDL subjected to oxidative modification have been well characterized and consist of degradation of polyunsaturated fatty acids, conversion of phospholipids to their lysoderivatives, nonenzymatic degradation of apolipoprotein B-100, and conjugation of fatty aldehydes to lysine residues in the protein moiety. 2 -6 These changes result in an LDL that is recognized by the macrophage scavenger receptor and possibly also by other receptors, leading to increased macrophage uptake of the modified LDL. 7 -8 In parallel, there may be a change in the monocyte and macrophage distribution pattern in the vicinity of the arterial wall, Received August 11, 1989; revision accepted June 29, 1990. resulting in an increase in intimal macrophages. 910These profound changes have been attributed to the oxidation process, and the finding that the antioxidant, probucol, could prevent these changes in vitro gives further support to this hypothesis. 11 It has also been reported that treatment of Watanabe heritable hyperlipidemic (WHHL) rabbits with probucol can prevent progression of atherosclerosis.12 A complication in the evaluation of the mechanism behind the antiatherogenic effect of probucol in vivo, however, is that this drug has an intrinsic hypolipidemic effect, which in itself could be ...

Patients perceived a higher grade of quality of care as compared to controls with no signs of disadvantages when treated and informed by supervised interprofessional student teams.

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