More about masitinib

A dose-escalating phase II trial studied masitinib, an oral tyrosine kinase inhibitor, in 43 patients with rheumatoid arthritis. Masitinib induced American College of Rheumatology (ACR)20, ACR50 and ACR70 responses in 54%, 26% and 8% of patients, respectively. A placebo group was not included. Thirty-seven per cent of the patients withdrew before the 12-week end-point was reached, primarily because of adverse events. These findings are the first on the efficacy of tyrosine kinase inhibition in a sizeable population. Future work should focus on delineating the tyrosine kinase that is most important in maintaining rheumatoid activity and address potential long-term toxicities such as gonadal insufficiency, teratogenicity and cardiotoxicity

The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index

Background Validity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised. Methods Three investigators assigned an activity score on a 0–10 scale for 97 clinical charts. The median score served as gold standard. Two other investigators labelled the disease as inactive/moderately active or active/very active. Univariate–multivariate linear regression analyses were used to define variables predicting the ‘gold standard’, their weight and derive an activity index. The cut-off point of the index best separating active/very active from inactive/moderately active disease was identified by a receiver-operating curve analysis. The index was validated on a second set of 60 charts assessed by three different investigators on a 0–10 scale and defined as inactive/moderately active or active/very active by other two investigators. One hundred and twenty-three were investigated for changes over time in the index and their relationships with those in the summed Medsger severity score (MSS). Results A weighted 10-point activity index was identified and validated: Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) \u3e18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein \u3e1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted \u3c70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease. Changes in the index paralleled those of MSS (p=0.0001). Conclusions A preliminarily revised SSc activity index has been developed and validated, providing a valuable tool for clinical practice and observational studies

Competing exchange interactions on the verge of a metal-insulator transition in the two-dimensional spiral magnet Sr3_3Fe2_2O7_7

We report a neutron scattering study of the magnetic order and dynamics of the bilayer perovskite Sr$_3$Fe$_2$O$_7$, which exhibits a temperature-driven metal-insulator transition at 340 K. We show that the Fe$^{4+}$ moments adopt incommensurate spiral order below $T_\text{N}=115$ K and provide a comprehensive description of the corresponding spin wave excitations. The observed magnetic order and excitation spectra can be well understood in terms of an effective spin Hamiltonian with interactions ranging up to third nearest-neighbor pairs. The results indicate that the helical magnetism in Sr$_3$Fe$_2$O$_7$ results from competition between ferromagnetic double-exchange and antiferromagnetic superexchange interactions whose strengths become comparable near the metal-insulator transition. They thus confirm a decades-old theoretical prediction and provide a firm experimental basis for models of magnetic correlations in strongly correlated metals.Comment: PRL, in pres

Skeletal muscle mitochondrial DNA content and aerobic metabolism in patients with antiretroviral therapy-associated lipoatrophy

Objectives To assess whether mitochondrial dysfunction in skeletal muscle characterizes antiretroviral therapy (ART)-associated lipoatrophy (LA). Methods A cross-sectional study comparing HIV-infected, antiretroviral-treated patients with LA (n = 5; LA+) and without LA (n = 5; non-LA) was conducted. Positron emission tomography was used to measure blood flow, oxygen extraction and oxygen consumption in quadriceps femoris muscle during rest and aerobic exercise. Mitochondrial DNA (mtDNA) was quantified by PCR. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. All data are given as means ± SEM. Results Compared with the non-LA group, the LA+ group had significantly less limb fat and more intra-abdominal fat, but similar leg muscle mass. The LA+ group versus the non-LA group had reduced mtDNA content per nucleus in adipose tissue (173 ± 38 versus 328 ± 62; P = 0.067), but not in skeletal muscle (2606 ± 375 versus 2842 ± 309; P = 0.64). Perfusion in resting muscle (34 ± 7 versus 28 ± 6 mL/kg/min in the LA+ group versus the non-LA group; P = 0.5), and the mean absolute (277 ± 30 versus 274 ± 43 mL/kg/min, respectively; P = 0.95) and relative (10.6 ± 2.5- versus 11.9 ± 1.5-fold change, respectively; P = 0.67) increases in perfusion during exercise were similar between the groups. Oxygen consumption at rest (2.2 ± 0.7 versus 2.1 ± 0.3 mL/kg/min in the LA+ group versus the non-LA group; P = 0.9), and the mean absolute (14.6 ± 1.7 versus 24.3 ± 8.8 mL/kg/min, respectively; P = 0.3) and relative (10.3 ± 2.8- versus 11.7 ± 2.4-fold change, respectively; P = 0.73) exercise-induced increases in oxygen consumption were similar between the groups. The oxygen extraction fraction was comparable between the groups, both at rest and during exercise. Plasma lactate concentrations remained unchanged in both groups during exercise. Conclusions HIV-infected patients with ART-associated LA have similar mtDNA content in skeletal muscle and comparable skeletal muscle aerobic exercise metabolism to antiretroviral-treated non-lipoatrophic patient

Late-onset systemic sclerosis—a systematic survey of the EULAR scleroderma trials and research group database

Objective. The clinical course of SSc depends on subtype, organ involvement and age. Few data are reported on patients suffering from late-onset SSc. Methods. We analysed data from 8554 patients prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) group database. Late-onset SSc was defined as onset of non-RP disease features at or beyond 75 years of age. Disease characteristics, clinical features, disease course and mortality were evaluated. Results. A total of 123 patients with SSc onset at or beyond 75 years of age were identified. Compared with patients <75 years they had more frequently limited than diffuse SSc and a higher prevalence of anti-centromere autoantibodies. Fewer old patients had digital ulcers. The modified Rodnan's skin score, the prevalence of lung fibrosis and renal crisis did not differ significantly between groups. Pulmonary hypertension (PH) measured by echocardiography was more prevalent in the late-onset group, as well as arterial hypertension and diastolic dysfunction. Late-onset SSc remained a positive predictor for PH in multivariate analyses. No significant difference of the two groups in skin score or diffusion capacity was observed during follow-up. Mortality due to SSc was higher in the late-onset group, but the survival time from diagnosis was longer compared with the younger patients. Conclusion. Late-onset SSc shows a distinct clinical presentation and outcome. Patients with late-onset SSc suffer more frequently from the limited subtype and PH, but fewer patients have digital ulcers. PH may in part be determined by underlying cardiovascular diseas