Does addition of glucocorticoids to the initial therapy influence the later course of the disease in patients with early RA? Results from the Swiss prospective observational registry (SCQM)

The main goal of this study was to analyse whether initial addition of glucocorticoid to DMARD therapy influences the long-term course of the disease in patients with early rheumatoid arthritis. All patients from the Swiss RA cohort SCQM with recent-onset arthritis (disease duration ≤1 year) were analysed. The exposure of interest was the use of glucocorticoids (GCs) at baseline. As primary outcome, we considered clinical and radiographic disease progression, assessed by the disease activity (disease activity score, DAS-28), function (health assessment questionnaire disability index, HAQ-DI) and structural joint damage (Ratingen erosion score). The baseline disease characteristics were compared using standard descriptive statistics. The effects of initial GC use on disease progression during follow-up were estimated using linear mixed models with random slope and random intercept, adjusted for potential confounders. In total, 592 patients with early disease were available, with 4.3 years of follow-up (average). Of these, 363 were initially treated with glucocorticoids (GC patients) and 228 were not (no-GC patients). DAS-28 (4.6 vs. 4.3, p = 0.01) and the HAQ-DI (0.94 vs. 0.82, p = 0.01) were higher at baseline in GC patients, while other prognostic factors were balanced at baseline. Neither the change of DAS-28, of HAQ-DI nor of the development of joint erosions differed between the two groups during follow-up. Escalation of treatment employing biologics was documented in 18.0% of the no-GC patients and 27.3% of the GC patients (p < 0.01). In this cohort, patients with early RA initially treated with GCs had higher measures of disease activity at baseline in comparison to no-GC patients. Despite a similar course of the disease in GC versus non-GC patients, the higher escalation rate to biologic agents in GC patients may reflect a disease less responsive to therapy in these patients. These data suggest that GC use as part of the initial therapeutic strategy in early RA may prevent a more severe course of the disease in patients with higher clinical disease measures at the start of therapy

Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol

Background: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients. Methods: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0–2–4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20–15–12.5–10–7.5–5–2.5–0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 &lt; 3.2). The primary objective was defined as the ACR 50 response at week 24. Results: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (p = 0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55). Conclusion: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy

Lieder und Weisen. 1 : disques d'enseignement / publiés sous la direction de Pierre Auclert, inspecteur principal de l'enseignement musical et d'Albert Spaeth, professeur d'Allemand, agrégé de l'Université

Titre uniforme : Schubert, Franz (1797-1828). Compositeur. [Erlkönig. D 328]Titre uniforme : Brahms, Johannes (1833-1897). Compositeur. [Sandmännchen. WoO 31, no 4]Titre uniforme : Loewe, Carl (1796-1869). Compositeur. [Der Erlkönig. Op. 1, no 3]Comprend : Die Lorelei / orchestre de l'Opéra de Berlin ; H. Schlusnus, BAR ; Der Erlkönig / Franz Schubert, comp. ; H. Schlusnus, BAR ; Franz Rupp, p ; Sandmännchen / Johannes Brahms, comp. ; N. Wetchor, S ; Pierre Auclert, p ; Das Männlein im Walde / Petits chanteurs de Vienne, ens. voc. ; Orchestre symphonique de Vienne ; Der Erlkönig / Carl Loewe, comp. ; H. Schey, BAR ; F. de Nobel, pBnF-Partenariats, Collection sonore - BelieveContient une table des matière

Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone

Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF). We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs) in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 μg/kg) or in combination with a single dose (106 cells) of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min) of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration.” However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time