Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.

To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. The clinical course of varicella and herpes zoster in children under immunosuppression is variable, with 4 (18 %) of 22 children showing a complicated course. Thorough assessment of VZV disease and vaccination history and correct VZV vaccination according to national guidelines at diagnosis of a rheumatic autoimmune disease is essential to minimize VZV complications during a later immunosuppressive treatment

Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1

Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss of trans-epithelial resistance (TER). Significantly, TGF-beta1-mediated EMT was markedly blunted in epithelial cells lacking JNK1, while JNK2-/- MTEC underwent EMT in response to TGF-beta1 in a similar way to wild-type cells. Although Smad2/3 phosphorylation and nuclear localization of Smad4 were similar in JNK1-/- MTEC in response to TGF-beta1, Smad DNA-binding activity was diminished. Gene expression profiling demonstrated a global suppression of TGF-beta1-modulated genes, including regulators of EMT in JNK1-/- MTEC, in comparison with wild-type cells. In aggregate, these results illuminate the novel role of airway epithelial-dependent JNK1 activation in EMT

First AMBER/VLTI observations of hot massive stars

AMBER is the first near infrared focal instrument of the VLTI. It combines three telescopes and produces spectrally resolved interferometric measures. This paper discusses some preliminary results of the first scientific observations of AMBER with three Unit Telescopes at medium (1500) and high (12000) spectral resolution. We derive a first set of constraints on the structure of the circumstellar material around the Wolf Rayet Gamma2 Velorum and the LBV Eta Carinae

An overview of the mid-infrared spectro-interferometer MATISSE: science, concept, and current status

MATISSE is the second-generation mid-infrared spectrograph and imager for the Very Large Telescope Interferometer (VLTI) at Paranal. This new interferometric instrument will allow significant advances by opening new avenues in various fundamental research fields: studying the planet-forming region of disks around young stellar objects, understanding the surface structures and mass loss phenomena affecting evolved stars, and probing the environments of black holes in active galactic nuclei. As a first breakthrough, MATISSE will enlarge the spectral domain of current optical interferometers by offering the L and M bands in addition to the N band. This will open a wide wavelength domain, ranging from 2.8 to 13 um, exploring angular scales as small as 3 mas (L band) / 10 mas (N band). As a second breakthrough, MATISSE will allow mid-infrared imaging - closure-phase aperture-synthesis imaging - with up to four Unit Telescopes (UT) or Auxiliary Telescopes (AT) of the VLTI. Moreover, MATISSE will offer a spectral resolution range from R ~ 30 to R ~ 5000. Here, we present one of the main science objectives, the study of protoplanetary disks, that has driven the instrument design and motivated several VLTI upgrades (GRA4MAT and NAOMI). We introduce the physical concept of MATISSE including a description of the signal on the detectors and an evaluation of the expected performances. We also discuss the current status of the MATISSE instrument, which is entering its testing phase, and the foreseen schedule for the next two years that will lead to the first light at Paranal.Comment: SPIE Astronomical Telescopes and Instrumentation conference, June 2016, 11 pages, 6 Figure

Direct constraint on the distance of y2 Velorum from AMBER/VLTI observations

In this work, we present the first AMBER observations, of the Wolf-Rayet and O (WR+O) star binary system y2 Velorum. The AMBER instrument was used with the telescopes UT2, UT3, and UT4 on baselines ranging from 46m to 85m. It delivered spectrally dispersed visibilities, as well as differential and closure phases, with a resolution R = 1500 in the spectral band 1.95-2.17 micron. We interpret these data in the context of a binary system with unresolved components, neglecting in a first approximation the wind-wind collision zone flux contribution. We show that the AMBER observables result primarily from the contribution of the individual components of the WR+O binary system. We discuss several interpretations of the residuals, and speculate on the detection of an additional continuum component, originating from the free-free emission associated with the wind-wind collision zone (WWCZ), and contributing at most to the observed K-band flux at the 5% level. The expected absolute separation and position angle at the time of observations were 5.1±0.9mas and 66±15° respectively. However, we infer a separation of 3.62+0.11-0.30 mas and a position angle of 73+9-11°. Our analysis thus implies that the binary system lies at a distance of 368+38-13 pc, in agreement with recent spectrophotometric estimates, but significantly larger than the Hipparcos value of 258+41-31 pc

Tigecycline in critically ill patients on continuous renal replacement therapy: a population pharmacokinetic study

Background: Tigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking. Methods: Eleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n = 8) or hemodiafiltration (CVVHDF, n = 3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. Results: A two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45–94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69 L/h, CLCVVHDF: 2.71 L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3 L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ≥ 0.88 for minimal inhibitory concentration (MIC) values ≤ 0.5 mg/L and similar to patients without AKI. Conclusions: Despite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT. Trial registration: EudraCT, 2012–005617-39. Registered on 7 August 2013

Near-Infrared interferometry of Eta Carinae with high spatial and spectral resolution using the VLTI and the AMBER instrument

We present the first NIR spectro-interferometry of the LBV Eta Carinae. The K band observations were performed with the AMBER instrument of the ESO Very Large Telescope Interferometer using three 8.2m Unit Telescopes with baselines from 42 to 89m. The aim of this work is to study the wavelength dependence of Eta Car's optically thick wind region with a high spatial resolution of 5 mas (11 AU) and high spectral resolution. The medium spectral resolution observations (R=1,500) were performed in the wavelength range around both the HeI 2.059 micron and the Br gamma 2.166 micron emission lines, the high spectral resolution observations (R=12,000) only in the Br gamma line region. In the K-band continuum, a diameter of 4.0 +/-0.2 mas (Gaussian FWHM, fit range 28-89m) was measured for Eta Car's optically thick wind region. If we fit Hillier et al. (2001) model visibilities to the observed AMBER visibilities, we obtain 50 % encircled-energy diameters of 4.2, 6.5 and 9.6mas in the 2.17 micron continuum, the HeI, and the Br gamma emission lines, respectively. In the continuum near the Br gamma line, an elongation along a position angle of 120+/-15 degrees was found, consistent with previous VLTI/VINCI measurements by van Boekel et al. (2003). We compare the measured visibilities with predictions of the radiative transfer model of Hillier et al. (2001), finding good agreement. Furthermore, we discuss the detectability of the hypothetical hot binary companion. For the interpretation of the non-zero differential and closure phases measured within the Br gamma line, we present a simple geometric model of an inclined, latitude-dependent wind zone. Our observations support theoretical models of anisotropic winds from fast-rotating, luminous hot stars with enhanced high-velocity mass loss near the polar regions.Comment: 22 pages, 14 figures, 2 tables; A&A in pres

Paediatric refugees from Ukraine: guidance for health care providers

BACKGROUND: With the invasion of Ukraine by the Russian Army in February 2022, refugees, the majority of whom are women and children, started fleeing the war to neighbouring countries. Even before the current escalation, the conflict in the eastern part of Ukraine has led to the internal displacement of more than 200,000 children, and many others have experienced attacks, e.g. on schools. This inevitably leads to limitations in health care delivery. During transit, overcrowding, poor shelter and vulnerability may further put refugees at increased risk for infectious diseases. This consensus document aims to provide information and guidance regarding health issues that paediatricians and general practitioners may face when caring for Ukrainian children. METHODS: Members of the Migrant Health Reference Group of Paediatrics Switzerland and the Paediatric Infectious Disease Group in Switzerland developed this recommendation between March and April 2022 in a modified Delphi process. RESULTS: A total of 50 recommendations were agreed on with a >/=80% consensus. These include the following topics: i) general aspects, including interpreter services, urgent health needs, personal history and general check-ups; ii) mental health, including how to search for signs of psychological distress without going into traumatic details; iii) vaccinations, including recommendations for evaluation and catch-up; iv) screening for tuberculosis, human immunodeficiency virus, and hepatitis B and C; and v) providing age-appropriate preventive and health service information. CONCLUSION: This document provides current evidence and guidance when caring for paediatric refugees from Ukraine. The recommendations focus on Switzerland but may well be used in other countries. These are based on current evidence and may need to be adapted to individual situations and once further evidence becomes available

Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Background: Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. Methods. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. Results: During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Conclusions: Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong. © 2011 Chan et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex