Development of practice and consensus-based strategies including a treat-to-target approach for the management of moderate and severe juvenile dermatomyositis in Germany and Austria

Background: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM. Methods: The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements. Results: Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-totarget strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease. Conclusion: Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM

Influenza Virus A Infection of Human Monocyte and Macrophage Subpopulations Reveals Increased Susceptibility Associated with Cell Differentiation

Influenza virus infection accounts for significant morbidity and mortality world-wide. Interactions of the virus with host cells, particularly those of the macrophage lineage, are thought to contribute to various pathological changes associated with poor patient outcome. Development of new strategies to treat disease therefore requires a detailed understanding of the impact of virus infection upon cellular responses. Here we report that human blood-derived monocytes could be readily infected with the H3N2 influenza virus A/Udorn/72 (Udorn), irrespective of their phenotype (CD14++/CD16−, CD14++/CD16+ or CD14dimCD16++), as determined by multi-colour flow cytometry for viral haemagglutinin (HA) expression and cell surface markers 8–16 hours post infection. Monocytes are relatively resistant to influenza-induced cell death early in infection, as approximately 20% of cells showed influenza-induced caspase-dependent apoptosis. Infection of monocytes with Udorn also induced the release of IL-6, IL-8, TNFα and IP-10, suggesting that NS1 protein of Udorn does not (effectively) inhibit this host defence response in human monocytes. Comparative analysis of human monocyte-derived macrophages (Mph) demonstrated greater susceptibility to human influenza virus than monocytes, with the majority of both pro-inflammatory Mph1 and anti-inflammatory/regulatory Mph2 cells expressing viral HA after infection with Udorn. Influenza infection of macrophages also induced cytokine and chemokine production. However, both Mph1 and Mph2 phenotypes released comparable amounts of TNFα, IL-12p40 and IP-10 after infection with H3N2, in marked contrast to differential responses to LPS-stimulation. In addition, we found that influenza virus infection augmented the capacity of poorly phagocytic Mph1 cells to phagocytose apoptotic cells by a mechanism that was independent of either IL-10 or the Mer receptor tyrosine kinase/Protein S pathway. In summary, our data reveal that influenza virus infection of human macrophages causes functional alterations that may impact on the process of resolution of inflammation, with implications for viral clearance and lung pathology

Three-dimensional cathodoluminescence imaging and electron backscatter diffraction: tools for studying the genetic nature of diamond inclusions

As a step towards resolving the genesis of inclusions in diamonds, a new technique is presented. This technique combines cathodoluminescence (CL) and electron backscatter diffraction (EBSD) using a focused ion beam-scanning electron microscope (FIB-SEM) instrument with the aim of determining, in detail, the three-dimensional diamond zonation adjacent to a diamond inclusion. EBSD reveals that mineral inclusions in a single diamond have similar crystallographic orientations to the host, within ±0. 4°. The chromite inclusions record a systematic change in Mg# and Cr# from core to the rim of the diamond that corresponds with a ~80°C decrease of their formation temperature as established by zinc thermometry. A chromite inclusion, positioned adjacent to a boundary between two major diamond growth zones, is multi-faceted with preferred octahedral and cubic faces. The chromite is surrounded by a volume of non-luminescent diamond (CL halo) that partially obscures any diamond growth structures. The CL halo has apparent crystallographic morphology with symmetrically oriented pointed features. The CL halo is enriched in ~200 ppm Cr and ~80 ppm Fe and is interpreted to have a secondary origin as it overprints a major primary diamond growth structure. The diamond zonation adjacent to the chromite is complex and records both syngenetic and protogenetic features based on current inclusion entrapment models. In this specific case, a syngenetic origin is favoured with the complex form of the inclusion and growth layers indicating changes of growth rates at the diamond-chromite interface. Combined EBSD and 3D-CL imaging appears an extremely useful tool in resolving the ongoing discussion about the timing of inclusion growth and the significance of diamond inclusion studies. © 2010 The Author(s)

Millennium-scale volcanic impact on a superhumid and pristine ecosystem

Ecosystems damaged by distal volcanic ash and sulfur deposition usually recover within decades. However, sediment, stalagmite, and pollen records from the southernmost Andes indicate a 2000 yr impact on forest and aquatic ecosystems after deposition of a thin tephra layer. SO2 released from altering pumice produced intense soil and lake acidification in a >150,000 km2 area. Acidification led to nutrient leaching and affected soil microorganisms, causing plant decay and increased soil erosion in an area larger than 8000 km2. We conclude that weakly buffered soils in humid environments are extremely vulnerable to volcanic and anthropogenic acidification, causing long-lasting ecosystem damage and perturbations of paleoclimate proxy records

Paleoecological constraints on Late Glacial to Holocene ice retreat in the Southern Andes (53°S)

Late Glacial to Holocene ice retreat was investigated along a 120 km long fjord system, reaching from Gran Campo Nevado (GCN) to Seno Skyring in the southernmost Andes (53°S). The aim was to improve the knowledge on regional and global control on glacier recession with special emphasis on latitudinal shifting of the westerlies. The timing of ice retreat was derived from peat and sediment cores, using mineralogical and chemical characteristics, and pollen as proxies. Stratigraphy was based on 14C-AMS ages and tephrochronology. The ice retreat of the Seno Skyring Glacier lobe is marked by an ice rafted debris layer which was formed around 18,300 to 17,500 cal. yr B.P. Subsequently, fast glacier retreat occurred until around 15,000 to 14,000 cal. yr B.P. during which around 84% of Skyring Glacier were lost. This fast recession was probably also triggered by an increase of the Equilibrium Line Altitude (ELA) from 200 to 300 m. Subsequently, the ice surface was lowered below the ELA in an area that previously made up more than 50% of the accumulation area. Much slower retreat and glacier fluctuations of limited extent in the fjord channel system northeast of GCN occurred between around 14,000 to 11,000 cal. yr B.P. during both the Antarctic Cold Reversal and the Younger Dryas. This slow down of retreat indicates a decline in the general warming trend and/or increased precipitation, due to a southward migration of the westerlies. After around 11,000 cal. yr B.P. pollen distribution shows evolved Magellanic Rainforest and similar climate as at present, which lasted throughout most of the Holocene. Only Late Neoglacial moraine systems were formed in the period 1220–1460 AD, and subsequently in the 1620s AD, and between 1870 and 1910 AD. The results indicate that the Gran Campo Nevado ice cap has reacted more sensitive and partly distinct to climate change, compared to the Patagonian Ice Field