EULAR definition of difficult-to-treat rheumatoid arthritis

Background: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have ‘difficult-to-treat RA’. However, uniform terminology and an appropriate definition are lacking. Objective: The Task Force in charge of the „Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis” aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to treat RA, as the first step. Methods: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). Results: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: 1) Treatment according to EULAR rec-ommendation and failure of ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy (unless contraindicated); 2) presence of at least one of the follow-ing: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; 3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. Conclusions: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research

Deficiências minerais em plantas de bertalha ( Basella alba, L.)

Basella alba is used as a major food on the Amazon region, north Brazil for its high mineral and vitamins content. The purpose of the present work was: a) obtain a clear picture of the macronutrient deficiency; b) growth of the plants in function of (1); c) analyptical levels found in the leaves. Young Basella alba plants (bertalha in Portuguese) were cultivated in pots containing fine pure quartz and irrigated by percolation with different nutrient solutions lacking one of the element at the time. Clear cut symptoms were obtained for all macronutrients. Only the omission of nitrogen and potassium affect the dry matter production of plants. The range in dry matter for unhealthy and healthy leaves were: N% = 1.25--3-55; P% = 0.17-0.36; K% = 0.46-3.55; Ca% = 0,62-1.78; Mg% = 0.37-0.80; S% = 0.19-0.13.Plantas de bertalha (Basella alba, L.) INPA-1 foram cultivadas em casa de vegetação em quartzo moído, irrigadas com soluções nutritivas conforme SARRUGE (1975) e submetidas aos seguintes tratamentos: completo, omissão de N, omissão de P, omissão de K, omissão de Ca, omissão de Mg e omissão de S, com o objetivo de: (a) obter sintomas de deficiência dos ma cronutrientes; (b) analisar o crescimento das plantas através da produção de matéria seca; (c) determinar a concentração dos macronutrientes nas folhas e caules das plantas cultivadas nos diversos tratamentos. Os sintomas visuais de deficiência foram identificados e descritos. As plantas foram coletadas e separadas em raiz, caule, folhas e determinaram-se os teores dos macronutrientes minerais neste material. Os resultados obtidos mostram: - os sintomas visuais de deficiência são bem definidos e de fácil caracterização para todos os nutrientes; - só foi possível detectar efeito na produção de matéria seca das folhas e caules para omissão de nitrogênio e para omissão de potássio nos caules; - os níveis de deficiência e adequação obtidos nas folhas foram respectivamente: N% = 1,25 e 2,63; P% = 0,17 e 0,36; K% = 0,46 e 3,55; Ca% = 0,62e 1,78; Mg% = 0,37 e 0,80; s%= 0,19 e 0,23. - os níveis de deficiência e adequação obtidos nos caules foram respectivamente: N% = 0,67 e 0,98; P% = 0,13 e 0,31; K% = 0,73 e 2,67; Ca% = 0,11 e 0,64; Mg% = 0,08 e 0,20; S% = 0,15 e 0,20

EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis

Objective: To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). Methods: A EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies, D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree, 10 completely agree) of the PtCs were determined by the Task Force members. Results: Two overarching principles and eleven PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and nonpharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). Conclusions: These points to consider for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Pathogenesis of visna/maedi and caprine arthritis-encephalitis: new leads on the mechanism of restricted virus replication and persistent inflammation

Lentiviruses are unique retroviruses which cause diseases with long incubation periods and prolonged clinical courses. The prototype lentiviruses, visna/maedi of sheep and arthritis-encephalitis virus of goats (CAEV), infect cells of the monocyte-macrophage system and replicate at a restricted level in these cells. The virus life cycle is closely associated with maturational factors in the cells; monocytes support the early stages of the replication cycle which goes to completion only when the cells mature to macrophages. Virus replication in the monocyte-macrophage results in lesions characterized by mononuclear cell infiltration of the central nervous system (CNS), lungs, synovium and mammary gland and their draining lymph nodes.<p></p> Co-cultivation of sheep or goat lymphocytes with macrophages infected with visna or CAE viruses results in production of a unique interferon (LV-IFN). LV-IFN is a non-glycosylated protein of 54,000 to 64,000 daltons and has biological properties which have several implications for pathogenesis. Firstly, it retards the rate of maturation of monocytes and thus indirectly slows the rate of virus replication. Second, it restricts the rate of virus replication in mature macrophages by preventing virus maturation. Third, it induces expression of class II (Ia) antigens of the major histocompatibility complex on cells of macrophage lineage. Thus, by curtailing virus replication and enhancing expression of MHC class II antigens, LV-IFN may contribute to the induction and augmentation of the host's lymphoproliferative response to the virus

Stable chromosomal units determine the spatial and temporal organization of DNA replication

DNA replication occurs in mammalian cells at so-called replication foci occupying defined nuclear sites at specific times during S phase. It is an unresolved problem how this specific spatiotemporal organization of replication foci is determined. Another unresolved question remains as to what extent DNA is redistributed during S phase. To investigate these problems, we visualized the replicating DNA and the replication machinery simultaneously in living HeLa cells. Time-lapse analyses revealed that DNA was not redistributed to other nuclear sites during S phase. Furthermore, the results showed that DNA is organized into stable aggregates equivalent to replication foci. These aggregates, which we call sub-chromosomal foci, stably maintained their replication timing from S phase to S phase. During S-phase progression, the replication machinery sequentially proceeded through spatially adjacent sets of sub-chromosomal foci. These findings imply that the specific nuclear substructure of chromosomes and the order of their stable subunits determine the spatiotemporal organization of DNA replication

Guideline-compliant prescription of biologicals and possible barriers in dermatological practices in Bavaria.

Skin affections after sulfur mustard (SM) exposure include erythema, blister formation and severe inflammation. An antidote or specific therapy does not exist. Anti-inflammatory compounds as well as substances counteracting SM-induced cell death are under investigation. In this study, we investigated the benzylisoquinoline alkaloide berberine (BER), a metabolite in plants like berberis vulgaris, which is used as herbal pharmaceutical in Asian countries, against SM toxicity using a well-established in vitro approach. Keratinocyte (HaCaT) mono-cultures (MoC) or HaCaT/THP-1 co-cultures (CoC) were challenged with 100, 200 or 300 mM SM for 1 h. Post-exposure, both MoC and CoC were treated with 10, 30 or 50 mu M BER for 24 h. At that time, supernatants were collected and analyzed both for interleukine (IL) 6 and 8 levels and for content of adenylate-kinase (AK) as surrogate marker for cell necrosis. Cells were lysed and nucleosome formation as marker for late apoptosis was assessed. In parallel, AK in cells was determined for normalization purposes. BER treatment did not influence necrosis, but significantly decreased apoptosis. Anti-inflammatory effects were moderate, but also significant, primarily in CoC. Overall, BER has protective effects against SM toxicity in vitro. Whether this holds true should be evaluated in future in vivo studies