Chronisch krank: Wenn sich die Gelenkinnenhaut entzündet : Therapieansätze aus der molekularen Medizin zeigen Erfolge

Etwa 800 000 Bundesbürger leiden an rheumatoider Arthritis (RA), der häufigsten chronisch-entzündlichen Erkrankung der Gelenke. Obwohl die Forschung in den vergangenen Jahren erhebliche Fortschritte gemacht hat, sind die Ursachen dieser schmerzhaften, bisher unheilbaren Krankheit noch nicht im Einzelnen geklärt. In vielerlei Richtungen diskutiert wird eine Fehlsteuerung des Immunsystems, bei der körpereigene Gewebsmatrix, wie der Gelenkknorpel, von Zellen des Immunsystems angegriffen wird. Die Forschungen der Mediziner, auch der Frankfurter Gruppe, konzentrieren sich weltweit auf die entzündungsfördernden Faktoren, spezielle Zytokine, und die Hemmstoffe dieser Zytokine. Aus diesen Ansätzen resultieren die neuartigen "Biologics": gentechnisch hergestellte monoklonale Antikörper, die natürlich vorkommenden Wirkstoffen entsprechen. Sie richten sich spezifisch gegen bestimmte vom menschlichen Organismus gebildete Zytokine

Assessment of mobilization capacity in 10 different ICU scenarios by different professions

Background: Mobilization of intensive care patients is a multi-professional task. Aim of this study was to explore how different professions working at Intensive Care Units (ICU) estimate the mobility capacity using the ICU Mobility Score in 10 different scenarios. Methods: Ten fictitious patient-scenarios and guideline-related knowledge were assessed using an online survey. Critical care team members in German-speaking countries were invited to participate. All datasets including professional data and at least one scenario were analyzed. Kruskal Wallis test was used for the individual scenarios, while a linear mixed-model was used over all responses. Results: In total, 515 of 788 (65%) participants could be evaluated. Physicians (p = 0.001) and nurses (p = 0.002) selected a lower ICU Mobility Score (-0.7 95% CI -1.1 to -0.3 and -0.4 95% CI -0.7 to -0.2, respectively) than physical therapists, while other specialists did not (p = 0.81). Participants who classified themselves as experts or could define early mobilization in accordance to the "S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders" correctly selected higher mobilization levels (0.2 95% CI 0.0 to 0.4, p = 0.049 and 0.3 95% CI 0.1 to 0.5, p = 0.002, respectively). Conclusion: Different professions scored the mobilization capacity of patients differently, with nurses and physicians estimating significantly lower capacity than physical therapists. The exact knowledge of guidelines and recommendations, such as the definition of early mobilization, independently lead to a higher score. Interprofessional education, interprofessional rounds and mobilization activities could further enhance knowledge and practice of mobilization in the critical care team

Expression of interleukin-18 receptor in fibroblast-like synoviocytes

An excess of the proinflammatory substance IL-18 is present in joints of patients with rheumatoid arthritis (RA), and expression of IL-18 receptor (IL-18R) regulates IL-18 bioactivity in various cell types. We examined the expression of IL-18R α-chain and β-chain and the biologic effects of IL-18 in fibroblast-like synoviocytes (FLS) after long-term culture. The presence of both IL-18R chains was a prerequisite for IL-18 signal transduction in FLS. However, all FLS cultures studied were either resistant or barely responsive to IL-18 stimulation as regards cell proliferation, expression of adhesion molecules ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and the release of interstitial collagenase and stromelysin, IL-6 and IL-8, prostaglandin E(2), or nitric oxide. We conclude that the presence of macrophages or IL-18R(+) T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA

Iron and the anaemia of chronic disease: a review and strategic recommendations.

BACKGROUND: The incidence of anaemia is high in many chronic conditions, yet it often receives little attention. SCOPE/METHODS: A panel of international experts with experience in haematology, nephrology, oncology, rheumatology and pharmacy was convened to prepare strategic guidelines. A focused literature search was conducted after key issues had been identified. A series of recommendations was agreed, backed, wherever possible, by published evidence which is included in the annotations. RECOMMENDATIONS: Anaemia is a critical issue for patients with chronic diseases. Healthcare professionals need to recognise that anaemia is a frequent companion of cancer and chronic conditions such as rheumatoid arthritis and heart failure. It reduces patients' quality of life and can increase morbidity and mortality. Anaemia should be considered as a disordered process in which the rate of red cell production fails to match the rate of destruction which leads eventually to a reduction in haemoglobin concentration; this process is common to all chronic anaemias. The aim of anaemia management should be to restore patient functionality and quality of life by restoring effective red cell production. Blood transfusion can elevate haemoglobin concentration in the short term but does nothing to address the underlying disorder; red cell transfusion is, therefore, not an appropriate treatment for chronic anaemia. Patients with anaemia of chronic disease may benefit from iron therapy and/or erythropoiesis stimulating agents (ESAs). Intravenous iron should be considered since this can be given safely to patients with chronic diseases while intramuscular iron causes unacceptable adverse effects and oral iron has limited efficacy in chronic anaemia. CONCLUSION: The management of anaemia calls for the development of a specialist service together with education of all healthcare professionals and transfer of skills from areas of good practice. Improvement in the management of anaemia requires a fundamental change of attitude from healthcare professionals

Alefacept plus methotrexate for psoriatic arthritis

Background Psoriatic arthritis (PsA) is a multifactorial condition that leads to chronic inflammation of the joints and entheses in around 10–30% of patients with psoriasis. Therapy for PsA is generally based around agents used to treat rheumatoid arthritis (RA), but toxicity and variability in treatment response limit their use, especially in the long term. Following recent research into the underlying immunologic nature of PsA, interest has focused on the modification of T-cell function. Alefacept, an inhibitor of T-cell activation approved for the treatment of chronic plaque psoriasis, has shown promising results in pilot studies in PsA. Objectives To investigate the efficacy and safety of alefacept in combination with methotrexate for the treatment of PsA. Design This was a placebo-controlled, double-blind, international phase II clinical trial. Eligible patients were 18–20 years old, with active PsA (greater than or equal to3 swollen joints and greater than or equal to3 tender joints), and were receiving stable doses of methotrexate (total duration of methotrexate treatment greater than or equal to3 months). Intervention Patients received weekly doses of either alefacept 15 mg or placebo intramuscularly for 12 weeks. This was followed by a 12-week, methotrexate-only observation period. All patients continued on their stable methotrexate dose (10–25 mg/week) throughout. Patients were stratified according to psoriasis body surface area (BSA) involvement (greater than or equal to3% o