Rubinfranck9035

Interferon-alpha seems to be the best initial treatment for ECD. Since 2012, more than 200 patients worldwide with multi-system or refractory ECD have benefitted from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have an overall, robust and reproducible efficacy in ECD, with no acquired resistance to date, but their use may be best reserved for the most severe manifestations of the disease, as they may be associated with serious side-effects and as yet unknown long-term consequences. Copyright © 2020 American Society of Hematology.INTRODUCTION Adipose tissue (AT) alterations are common in people living with HIV (PLWH). Decreases in AT density suggest disrupted adipocyte function/hypertrophy. Selleck Tacrolimus We assessed changes in AT density after antiretroviral therapy (ART) initiation and associations with immuno-metabolic parameters. METHODS In a prospective randomized clinical trial of ART initiation, L4-L5 abdominal CT scans measured subcutaneous (SAT) and visceral (VAT) AT area and density in treatment-naïve PLWH randomized to tenofovir-emtricitabine plus atazanavir-ritonavir, darunavir-ritonavir, or raltegravir. Linear regression models compared weeks 0 (W0) and 96 (W96) levels, and 96-week changes, in SAT and VAT density (in Hounsfield units, HU). Spearman's correlations assessed relationships between AT density and immuno-metabolic parameters. RESULTS Participants (n=228) were 89% male and 44% white non-Hispanic. Median age was 36 years, baseline HIV-1 RNA 4.6 log10 copies/mL, and CD4+ T cell count 344 cells/mm3. Over 96 weeks, SAT and VAT HU decreased significantly in all arms. Less dense W96 SAT and VAT density correlated with higher HDL cholesterol and adiponectin (r=0.19 to 0.30) levels and lower IL-6, non-HDL cholesterol, triglyceride, leptin and HOMA-IR (r=-0.23 to -0.68) levels at W96 after adjusting for baseline CD4+ T cell count, HIV-1 RNA and baseline AT area. CONCLUSIONS Following virologic suppression, lower SAT and VAT density was associated with greater plasma measures of systemic inflammation, lipid disturbances and insulin resistance independent of AT area, suggesting changes in AT density with ART may lead to adverse health outcomes independent of AT quantity. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Hemophagocytic lymphohistiocytosis (HLH) is a syndrome describing patients with severe systemic hyperinflammation. Characteristic features include unremitting fever, cytopenias, hepatosplenomegaly, and elevation of typical HLH biomarkers. Patients can develop hepatitis, coagulopathy, liver failure, central nervous system involvement, multi-organ failure, and other manifestations. The syndrome has a high mortality rate. More and more, it is recognized that while HLH can be appropriately used as a broad summary diagnosis, many pediatric patients actually suffer from an expanding spectrum of genetic diseases that can be complicated by the syndrome of HLH. Classic genetic diseases in which HLH is a typical and common manifestation include pathogenic changes in the Familial HLH genes (PRF1, UNC13D, STXBP2, STX11), several granule/pigment abnormality genes (RAB27A, LYST, AP3B1), the X-linked lymphoproliferative disease genes (SH2D1A, XIAP), and others such as NLRC4, CDC42, and the EBV-susceptibility diseases. There are many other genetic diseases in which HLH is an infrequent complication of the disorder as opposed to a prominent manifestation of the disease caused directly by the genetic defect, including other primary immune deficiencies and inborn errors of metabolism. HLH can also occur in patients with underlying rheumatologic or autoinflammatory disorders, and is usually designated macrophage activation syndrome in those settings. Additionally, HLH can develop in patients during infections or malignancies without a known (or as yet identified) genetic predisposition. This article will attempt to summarize current concepts in the pediatric HLH field as well as offer a practical diagnostic and treatment overview. Copyright © 2020 American Society of Hematology.BACKGROUND Having a penicillin allergy label is associated with the use of less appropriate and more expensive antibiotics and increased healthcare utilization. Penicillin allergy testing results in delabeling most allergy claimants and may be cost-saving. This study aimed to project whether penicillin allergy testing in patients reporting a penicillin allergy is cost-saving. METHODS In this economic evaluation study, we built decision models to project the economic impact of two strategies for the patient with a penicillin allergy label (1) Perform diagnostic testing (drug challenges, with or without skin tests) and (2) Do not perform diagnostic testing. The health service perspective was adopted, considering costs with penicillin allergy tests, and with hospital bed-days/outpatient visits, antibiotic use, and diagnostic testing. Twenty-four base case decision models were built, accounting for differences in the diagnostic workup, setting (inpatient versus outpatient) and geographic region. Uncertainty was explored via probabilistic sensitivity analyses. RESULTS Penicillin allergy testing was cost-saving in all decision models built. For models assessing the performance of both skin tests and drug challenges, allergy testing resulted in average savings of $657 for inpatients (United States of America $1444, Europe $489) and $2746 for outpatients (United States of America $256, Europe $6045). 75% of simulations obtained through probabilistic sensitivity analysis identified testing as the less costly option. CONCLUSION Penicillin allergy testing was projected to be cost-saving across different scenarios. These results are devised to inform guidelines, supporting the adoption of policies promoting widespread testing of patients with a penicillin allergy label. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.