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Available data have proved insufficient to develop consensus recommendations on the prevention of thrombosis and bleeding in myelofibrosis (MF). We evaluated the incidence and risk factors of vascular complications in 1613 patients from the Spanish Myelofibrosis Registry. Over a total of 6981 patient-years at risk, 6.4% of the study population had at least one thrombotic event after MF diagnosis, amounting to an incidence rate of 1.65 per 100 patient-years. Prior history of thrombosis, the JAK2 mutation, and the intermediate-2/high-risk International Prognostic Scoring System (IPSS) categories conferred an increased thrombotic risk after adjustment for the risk-modifying effect of anti-thrombotic and cytoreductive treatments. History of thrombosis and the JAK2 mutation allowed us to pinpoint a group of patients at higher risk of early thrombosis. No decreased incidence of thrombosis was observed while patients were on anti-thrombotic or cytoreductive treatment. An increased risk of venous thrombosis was found during treatment with immunomodulatory agents. A total of 5.3% of patients had at least one episode of major bleeding, resulting in an incidence rate of 1.5 events per 100 patient-years. Patients in the intermediate-2/high-risk IPSS categories treated with anti-coagulants had an almost sevenfold increased risk of major bleeding. These findings should prove useful for guiding decision-making in clinical practice.

Resumen del trabajo presentado al 3rd GLOBAL NASH Congress and Metaboloc syndrom, diabetes and NAFLD Symposium, celebrados del 10 al 11 de febrero de 2020 en Londres., Cell-to-cell communication by extracellular vesicles (EVs) is an emerging issue in non-alcoholic fatty liver disease (NAFLD). In this study we found higher EVs secretion, particularly exosomes, in hepatocytes and plasma from obese mice with NAFLD compared with the controls from lean mice. Moreover, both the uptake of NAFLD-exosomes by macrophages in culture and intravenous injection of NAFLD-exosomes in mice triggered NFκB activation and a proinflammatory response. Insulin resistance was induced in hepatocytes incubated with the secretome of macrophages treated with NAFLD exosomes and in cultured hepatocytes isolated from mice injected with NAFLD exosomes. Our results identified a novel molecular mechanism in the interactome hepatocyte-macrophagehepatocyte where NAFLD exosomes (circulating or hepatocyte-derived) induced inflammation and insulin resistance through macrophages inflammatory responses.

Background Atopic dermatitis is an allergic T-cell mediated skin inflammation. Staphylococcus aureus colonization is very common in cutaneous atopic dermatitis lesions. The cutaneous lymphocyte-associated antigen (CLA) is a T cell skin homing receptor that defines T lymphocytes associated with the cutaneous immune response. Objective To study whether CLA+ T cells from atopic dermatitis children present a selective expression for Staphylococcus aureus-related TCR Vβ segments. Methods Peripheral blood T cells were stained with HECA-452 (anti-CLA) and a panel of TCR Vβ specific monoclonal antibodies and analysed by flow cytometry. Results Atopic dermatitis patients have a higher percentage of circulating CLA+ CD3+ lymphocytes compared with healthy controls. Patients with active atopic dermatitis during the study expressed a higher percentage of cells positive for the TCR Vβ2 and Vβ5.1 segments in the CLA+ but not in the CLA− subset. These TCR Vβs are recognized by staphylococcal superantigens. Moreover, there was an increased percentage of HLA-DR+ expression by CLA+ Vβ5.1+ T cells in patients with active atopic dermatitis, but those patients whose eczema was inactive had very similar values to healthy controls regarding TCR Vβ and HLA-DR phenotype in circulating CLA+ T lymphocytes. Conclusion Our data indicate that circulating skin-homing T cells of patients with active atopic dermatitis contain an increased percentage of cells bearing TCR Vβ segments related with Staphylococcus aureus. Staphylococcus superantigens may therefore trigger expansion or at least circulation of appropriate CLA+ T cells.

Treatment with growth hormone in children is a very effective promotor of growth. The psychosocial environment of children may influence the results of this treatment. It has been shown that there is a clear relationship between the knowledge and understanding a child has of the treatment and the degree of compliance and acceptance. We have studied 90 children treated with growth hormone who filled in a questionnaire in order to know the knowledge and acceptance of their treatment. The scores for acceptance were significantly higher than for knowledge (p < 0.00001), without correlations between the two variables. The higher marks were achieved by children who had attended an educational camp. A serious lack of knowledge about the aspects directly related with the injection system was noted. We advise to design a suitable educational program for these patients.

Atopic dermatitis is an allergic T-cell mediated skin inflammation. Staphylococcus aureus colonization is very common in cutaneous atopic dermatitis lesions. The cutaneous lymphocyte-associated antigen (CLA) is a T cell skin homing receptor that defines T lymphocytes associated with the cutaneous immune response.To study whether CLA+ T cells from atopic dermatitis children present a selective expression for Staphylococcus aureus-related TCR Vbeta segments.Peripheral blood T cells were stained with HECA-452 (anti-CLA) and a panel of TCR Vbeta specific monoclonal antibodies and analysed by flow cytometry.Atopic dermatitis patients have a higher percentage of circulating CLA+ CD3+ lymphocytes compared with healthy controls. Patients with active atopic dermatitis during the study expressed a higher percentage of cells positive for the TCR Vbeta2 and Vbeta5.1 segments in the CLA+ but not in the CLA- subset. These TCR Vbetas are recognized by staphylococcal superantigens. Moreover, there was an increased percentage of HLA-DR+ expression by CLA+ Vbeta5.1+ T cells in patients with active atopic dermatitis, but those patients whose eczema was inactive had very similar values to healthy controls regarding TCR Vbeta and HLA-DR phenotype in circulating CLA+ T lymphocytes.Our data indicate that circulating skin-homing T cells of patients with active atopic dermatitis contain an increased percentage of cells bearing TCR Vbeta segments related with Staphylococcus aureus. Staphylococcus superantigens may therefore trigger expansion or at least circulation of appropriate CLA+ T cells.

Cytarabine (Cyt) is an antimetabolite used primarily in the treatment of leukemia, and both immediate and delayed hypersensitivity reactions have been reported. We studied a 9-year-old girl with lymphoblastic leukemia, who developed three anaphylactoid reactions during Cyt treatment courses over a 1-year period. Three years later, Cyt was required again. Although a skin test was negative to Cyt at the concentration of 4 micrograms/ml, we decided on placebo-controlled administration of the drug. The Cyt was well tolerated, and urine values of N-methylhistamine showed no important variations throughout this period compared to those during the placebo administration. Skin tests carried out 14 days after the study were positive at the concentration of 4 micrograms/ml. The history of different episodes of allergic reactions to Cyt, the last one being the most severe, indicated the possible participation of an immediate hypersensitivity phenomenon, but because no studies had been carried out initially, we could not establish the presence of IgE antibodies. These results indicate that good tolerance existed after the control administration procedure. The long interval, 3 years, between the allergic episode and our protocol and the appearance of a positive skin test 14 days after the protocol indicated that the subject had lost sensitivity and become resensitized after the controlled administration procedure.

Idiopathic pulmonary hemosiderosis (IPH) is characterized by repeated episodes of intraalveolar bleeding, hemosiderin deposition in alveolar macrophages, and subsequent development of pulmonary fibrosis and severe anemia? This disease predominantly affects children; the age of occurrence ranges from 4 months to 62 years, although cases in newborn infants have been described. 2 The pathologic mechanism is not well understood, but some evidence supports an immunopathologic basis. The association of IPH with hypersensitivity to cow's milk proteins was first reported by Heiner and Sears 3 who described patients with recurrent pulmonary disease, changing roentgenographic manifestations, hemoptysis, iron-laden macrophages in gastric or bronchial washings, iron deficiency anemia, and multiple precipitins to cow's milk. Additional studies have shown peripheral blood eosinophilia; alveolar deposits of IgG, IgA. and C3; circulating immune complexes: and delayed hypersensitivity to cow's milk proteins?- 5 We studied a newborn infant with IPH and myocardial involvement in whom the administration of cow's milk proteins induced peripheral eosinophilia and the release of histamine and eosinophilic cationic protein (ECP) in peripheral blood and bronchoalveolar lavage (BAL) and the release of histamine in urine.