Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts.

OBJECTIVE: A lack of representation in pivotal trials currently limits guidance for the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in psoriatic arthritis (PsA) patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with low vs high number of affected joints. METHODS: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or < 3 swollen joints or high joint count patients (HJC) with > =3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models. RESULTS: 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC were less often on conventional synthetic (cs) DMARDs. Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC in both crude and adjusted analyses (Hazard Ratio (HR) 1.09 [0.76-1.58], p= 0.52). Furthermore, bDMARD retention was significantly better (HR 0.63 [0.47-0.85], p< 0.002) when administered with csDMARD co-therapy. CONCLUSIONS: Biological DMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count.

The links of hepcidin and erythropoietin in the interplay of inflammation and iron deficiency in a large observational study of rheumatoid arthritis.

Anaemia affects quality of life and radiographic outcome in rheumatoid arthritis (RA). In a cross-sectional study with 779 patients, we assessed the prognostic potential of the major haematopoietic regulators, hepcidin and erythropoietin, comparing their serum concentrations with respect to different anaemia types, inflammatory activity, anti-cytokine-specific treatment effects and iron deficiency (ID) indices. The results showed that clinical disease activity was more closely associated with haemoglobin levels than with anti-tumour necrosis factor-alpha or interleukin 6 receptor effects. In ID, hepcidin was suppressed, independently of inflammation. Erythropoietin levels were inappropriately low in relation to the degree of anaemia, but, in contrast to low haemoglobin, not directly associated with joint damage progression. Hepcidin and erythropoietin levels are intimately connected with inflammation and ID. Interventional studies on these important targets are already in progress.

Cholesterol enhances thrombin-induced release of fibroblast growth factor-2 in human vascular smooth muscle cells.

OBJECTIVE: The mitogenic response to the G protein-coupled receptor agonist thrombin in human vascular smooth muscle cells (SMCs) depends on release of fibroblast growth factor-2 (FGF-2). Yet, intracellular mechanisms triggering FGF-2 release are unknown. The present study investigates possible effects of cholesterol enrichment and depletion, which have been shown to influence FGF-2-dependent signaling and SMC mitogenesis, on thrombin-induced FGF-2 release. METHODS AND RESULTS: Cultured human aortic and saphenous vein SMCs were enriched with cholesterol by using a cyclodextrin-cholesterol complex. Cholesterol accumulation was determined by a fluorometric assay. ELISA, Western blotting, and RT-PCR were used for quantification of FGF-2 levels. DNA synthesis was determined by [3H]-thymidine incorporation, proliferation by cell counting. Stimulation of SMCs with thrombin (30 nmol/L) resulted in release of FGF-2 into the pericellular space within 10 minutes. Preincubation with cyclodextrin-cholesterol caused accumulation of cellular cholesterol, increased thrombin-induced FGF-2 release, and stimulated FGF-2 de novo synthesis. Thrombin-induced DNA synthesis and proliferation were enhanced in cholesterol-rich SMCs. This effect was inhibited by FGF-2-neutralizing antibodies. CONCLUSIONS: Enhanced cellular cholesterol stimulates thrombin-induced release of FGF-2 and increases the mitogenic response toward thrombin in human SMCs. This mechanism might also be relevant for thrombin-induced mitogenesis in hypercholesterolemia in vivo.

Persisting right-sided chylothorax in a patient with chronic lymphocytic leukemia: a case report.

INTRODUCTION: Chylothorax caused by chronic lymphocytic leukemia is very rare and the best therapeutic approach, especially the role of modern immunochemotherapy, is not yet defined. CASE PRESENTATION: We present the case of a 65-year-old male Caucasian patient with right-sided chylothorax caused by a concomitantly diagnosed chronic lymphocytic leukemia. As first-line treatment four cycles of an immunochemotherapy, consisting of fludarabine, cyclophosphamide and rituximab were administered. In addition, our patient received total parenteral nutrition for the first two weeks of treatment. Despite the very good clinical response of the lymphoma to treatment, the chylothorax persisted and percutaneous radiotherapy of the thoracic duct was applied. However, eight weeks after the radiotherapy the chylothorax still persisted and our patient agreed to a surgical intervention. A ligation of the thoracic duct via a muscle sparing thoracotomy was performed, resulting in a complete cessation of the pleural effusion. Apart from the first two weeks our patient was treated on an out-patient basis for nearly six months. CONCLUSION: In this case of chylothorax caused by chronic lymphocytic leukemia, immunochemotherapy in combination with conservative treatment, and even consecutive radiotherapy, were not able to stop pleural effusion, despite the very good clinical response of the chronic lymphocytic leukemia to treatment.Out-patient management using repetitive thoracocenteses can be safe as bridging until definitive surgical ligation of the thoracic duct.