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Background Previous studies suggested that obesity could negatively affect the response to antitumour necrosis factor-α (TNFα) agents in rheumatoid arthritis (RA). However, data are lacking on whether obesity affects the response to abatacept (ABA). We aimed to determine whether body mass index (BMI) affects the response to ABA in RA. Materials and methods In this multicenter retrospective study, we included RA patients who received ABA. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, tender and swollen joint count were analysed. The primary endpoint was decrease in DAS28 ≥ 1·2. Secondary outcomes were good response and remission by EULAR criteria. Results At baseline, among 141 RA patients included, the median [interquartile range] BMI was 26·0 [22·9–30·8] kg/m². The number of patients with normal weight, overweight and obesity was 64 (45·4%), 38 (27%) and 39 (27·6%), respectively. Baseline characteristics did not differ among the three BMI subgroups. Univariate analysis revealed no difference in BMI between responders and nonresponders: DAS28 decrease ≥ 1·2 (25·0 [23·4–31·3] vs. 26·3 [22·9–30·2], P = 0·95), EULAR good response (26·4 [23·5–30·9] vs. 26·0 [22·9–30·6], P = 0·96) and remission (26·7 [21·7–30·3] vs. 26·0 [23·0–30·1], P = 0·83). Conclusion In our real-life study, BMI did not affect the response to ABA in RA. If confirmed, these results suggest that obesity is not a limitation of ABA use in RA.

OBJECTIVE While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). METHODS The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay. RESULTS We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. CONCLUSION The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses.

Objective Alsace is a region in eastern France with a population of ∼2 million. All residents have high access to health care and an accredited referral center for SSc. Seeking care outside of this region is difficult because of the peculiar geography. The aim of this study was to assess the prevalence and spatial variation of systemic sclerosis (SSc) in eastern France. Methods Data for SSc patients were obtained from 3 sources (all general practitioners and community specialists, capillaroscopy centers, and all public and private hospital records) and were used to estimate the prevalence of SSc. Surviving patients who resided in Alsace on January 1, 2008 and fulfilled the American College of Rheumatology and/or the LeRoy and Medsger criteria were included in this study. The clinical characteristics of the patients were also assessed. Potentially incomplete case ascertainment was corrected by capture–recapture analyses. Geographic disparities were assessed by spatial cluster analysis and by comparing our results with those for other geographic areas in the world for which data derived using similar methodology were available. Results The review of 499 potential cases identified a total of 244 SSc patients. A trend toward a west-to-east gradient was observed but did not reach statistical significance. According to log-linear modeling, an estimated 83.87 additional cases were missed. Thus, the SSc prevalence was 228.42 cases per million adult inhabitants of Alsace (95% confidence interval 203.70–253.14); this prevalence was significantly higher than that in 2 other regions of France and comparable with the reported prevalence in Detroit, Michigan. Conclusion The stringent methodology used in the current study is very likely to provide an accurate estimation of the prevalence of SSc. Design similarity with 3 other surveys extends the scope of the results by identifying geographic disparities that were previously indistinguishable due to methodologic differences.

Muscle dysfunction is a common complication and an important prognostic factor in chronic obstructive pulmonary disease (COPD). As therapeutic strategies are still needed to treat this complication, gaining more insight into the process that leads to skeletal muscle decline in COPD appears to be an important issue. This review focuses on mitochondrial involvement in limb skeletal muscle alterations (decreased muscle mass, strength, endurance and power and increased fatigue) in COPD. Mitochondria are the main source of energy for the cells; they are involved in production of reactive oxygen species and activate an important pathway that leads to apoptosis. In COPD patients, skeletal muscles are characterized by decreased mitochondrial density and biogenesis, impaired activity and coupling of mitochondrial respiratory chain complexes, increased mitochondrial production of reactive oxygen species and, possibly, increased apoptosis. Of particular interest, a sedentary lifestyle, hypoxia, hypercapnia, tobacco smoking, corticosteroid therapy and, possibly, inflammation participate in this mitochondrial dysfunction, which is accessible to conventional therapies, such as exercise and tobacco cessation, as well as, potentially, to more innovative approaches, such as antioxidant treatment and supplementation with polyunsaturated fatty acids.

Ageing is associated with skeletal muscle impairment. Changes in mitochondrial homeostasis are thought to play a key role in this process. This study examined whether chronic intake of polyphenols (PPs), which are known to be modulators of oxidative stress, might prevent the age-related decline of mitochondrial functions in skeletal muscle. Three groups of 10 Wistar rats were investigated. Rats aged 16 weeks were compared with rats aged 40 weeks that were given 75 mg kg(-1) day(-1) PPs or solvent in the drinking water starting at week 16. Mitochondrial respiratory chain complex activities were measured in saponin-skinned fibres of soleus muscles using glutamate-malate (V(max)), succinate (V(succ)) and N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride-ascorbate (V(TMPD)). Production of reactive oxygen species was assessed using dihydroethidium staining. Transcript levels of genes involved in antioxidant defence were determined using RT-PCR. Ageing reduced muscle V(max) (from 8.8 ± 0.45 to 6.17 ± 0.51 μmol O(2) min(-1) g(-1), -30.5%, P < 0.01), V(TMPD) (from 20.67 ± 1.24 to 16.55 ± 1.16 μmol O(2) min(-1) g(-1), -19.9%, P < 0.05), increased production of reactive oxygen species (from 100 ± 9.9 to 351.1 ± 31.7%) and decreased transcripts of mitochondrial superoxide dismutase 2 (-59.3%, P < 0.01), peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β; -61.5%, P < 0.05) and sirtuin 1 (-54.2%, P < 0.05). Chronic PP intake normalized V(max) (8.63 ± 0.63 μmol O(2) min(-1) g(-1)), decreased production of reactive oxygen species (141.7 ± 16.7%, P < 0.001) and enhanced antioxidant defence (superoxide dismutase 2 expression, +151.3%, P < 0.05) and PGC-1β expression (+185.7%, P < 0.05) in comparison to age-matched untreated rats. The present data indicate that regular intake of PPs starting at a young age prevents age-related mitochondrial respiratory impairment in skeletal muscle, probably through decreased oxidative stress and enhancement of PGC-1β expression.

BACKGROUND: Patient controlled epidural analgesia (PCEA) is uncommon in pediatric anesthesia. Because PCEA offers superior pain control compared with continuous epidural infusions in adults, we prospectively evaluated the analgesia efficacy and safety of PCEA in children and adolescents following extensive spinal surgery. METHODS: Following ethics committee approval, 100 consecutive children [age median (range) 14 (6-19) years] undergoing spinal surgery were studied until the seventh postoperative day, and 98 children received a PCEA. One or two epidural catheters were positioned under direct vision by the surgeon based on the number of vertebral segments operated upon. The epidural solution consisted of bupivacaine 0.0625%, fentanyl 1 microg.ml(-1) and clonidine 0.6 microg.ml(-1), delivered at a basal rate of 0.2 ml.kg(-1).h(-1) and a PCEA dose of 0.1 ml.kg(-1).h(-1)(max. 2 h(-1)). On the fourth postoperative day, PCEA was stopped and analgesia was continued with patient controlled analgesia (PCA) with morphine. RESULTS: During the PCEA regimen, the maximal scores of the revized facial scale were below 4 at rest with a very high satisfaction rate (>90%). Pain scores were higher during mobilization on the first postoperative day and when PCEA was switched to PCA. The overall incidence of adverse events was low and consisted primarily of technical problems and postoperative nausea and vomiting. Only two children experienced a complication requiring the discontinuation of the PCEA but there were no consequent adverse sequelae. CONCLUSIONS: The present study demonstrates that PCEA provides excellent pain relief following extensive spinal surgery and is associated with a low incidence of adverse events. The use of PCEA should be encouraged in children and adolescents following extensive spinal surgery.