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Vascular involvement in systemic sclerosis (SSc) plays a key role in the pathogenesis of fibrosis. We assessed arterial stiffness using a new echo-tracking technique in patients with SSc asymptomatic for cardiovascular diseases. We enrolled 22 patients (21 female, 63 ± 14 years) and 20 controls (12 female, 62 ± 3 years). Carotid intima-media thickness (IMT) was comparable between the 2 groups (1.1 ± 0.3 vs 1.0 ± 0.4 mm, P = ns), whereas the stiffness parameters were significantly increased in patients (β: 9.5 ± 4.2 vs 5.8 ± 1.1, P = .001; pulse wave velocity [PWV]: 6.5 ± 1.5 vs 5.2 ± 0.6 m/sec, P = .003). A correlation between stiffness parameters, anti-Scl-70 antibodies (β: r = .46, P = .03; PWV: r = .50, P = .02), and anticentromere antibodies (β: r = -.54, P = .020; PWV: r = -.53, P = .023) was found. Echo-tracking technique may be valuable in early identification of vascular involvement in patients with SSc.

Background and aims Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA. Methods and results CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen. Conclusions RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.

Individuals suffering from chronic pain are frequently affected by depression, which in turn increases the risk of developing chronic pain over time. This study aims to investigate the relationship between depression and pain intensity and threshold in a group of rheumatic patients compared to healthy subjects. One hundred twenty-four individuals of whom 50 were affected by rheumatoid arthritis (RA), 23 by psoriatic arthritis (PsA), 23 by ankylosing spondylitis (AS), and 28 age-matched controls without chronic pain underwent quantitative sensory testing to assess pressure pain threshold with pressure algometry. Pain intensity was evaluated through the visual analogue scale (VAS) and depression through the Hamilton Depression Rating scale (HAMD). A significant inverse correlation between HAMD values and pressure pain thresholds was found in the entire group of patients (p < 0.0001), in controls (p = 0.02), and also in RA (p = 0.002), PsA (p < 0.0002), and AS (p = 0.02) patients when analyzed separately, while no significant correlation was found between HAMD and VAS values or pressure pain thresholds and VAS. We found lower pain thresholds in RA and PsA patients while no difference has been evidenced in AS patients compared to healthy controls. HAMD scores were also significantly higher in rheumatic patients than in controls. The use of pressure algometry in the evaluation of chronic pain in patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis that display comorbid depression could represent an additional and integrative method to improve pain/depression overlap management or research.

A link between reactive oxygen species (ROS) and Systemic Sclerosis (SSc) development has been already described, along with an oxidative stress-induced reduction of anion exchange capability through Band 3 protein. On this basis, blood from SSc patients has been collected to measure the rate constant for SO4= uptake, which is an index for anion exchange capability through Band 3 protein. This parameter was significantly reduced in SSc patients, with or without Interstitial Lung Disease, a complication of SSc. As a reduced Band 3 protein function was observed in SSc patients with either low or high levels of malonildialdehyde (MDA), the end product of lipoperoxidation, anion exchange through erythrocytes membrane may be not univocally related to oxidative stress and, what is more, can be considered as a sensitive tool to monitor SSc development.

In systemic sclerosis (SSc) vasculopathy affects small arteries and capillaries, but recent evidences show also macrovascular alterations. Experimental data suggest that propylthiouracil (PTU) abrogates the development of cutaneous and pulmonary fibrosis during SSc. The aim of this study was to evaluate the effect of propylthiouracil on aortic lipid peroxidation, intima-media thickness and myofibroblasts differentiation in experimental SSc.SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) for 6weeks. Mice (n=25) were randomized to receive daily: HOCl (n=10), HOCl+PTU (n=10), or vehicle (n=5). Thoracic aorta was evaluated by histological methods to measure intima-media thickness and by immunostaining for α-smooth muscle actin (α-SMA) to assess myofibroblast differentiation. Aortic and plasma levels of malondialdehyde (MDA) were also measured.HOCl induced a significant increase in aortic intima-media thickness compared to controls (p0.001), while PTU administration prevented intima-media thickening (p0.01). Myofibroblast differentiation was also less evident in HOCl+PTU-treated animals (p0.05) compared to mice treated with HOCl alone. The increase in aortic and plasma MDA levels induced by HOCl, was significantly prevented by PTU administration (p0.05).PTU, by reducing lipid peroxidation, prevents aortic thickening and myofibroblast differentiation induced by HOCl, reducing macrovascular alterations in experimental SSc.

Recent advances suggest that the cellular redox state may play a significantrole in the progression of fibrosis in systemic sclerosis (SSc). Another,and as yet poorly accounted for, feature of SSc is its overlap with thyroidabnormalities. Previous reports demonstrate that hypothyroidism reducesoxidant stress. The aim of this study was therefore to evaluate the effectof propylthiouracil (PTU), and of the hypothyroidism induced by it, on thedevelopment of cutaneous and pulmonary fibrosis in the oxidant stress murinemodel of SSc. Chronic oxidant stress SSc was induced in BALB/c mice by daily subcutaneousinjections of hypochlorous acid (HOCl) for 6 weeks. Mice (n = 25)were randomized into three arms: HOCl (n = 10), HOCl plus PTU(n = 10) or vehicle alone (n = 5). PTU administrationwas initiated 30 minutes after HOCl subcutaneous injection and continueddaily for 6 weeks. Skin and lung fibrosis were evaluated by histologicmethods. Immunohistochemical staining for alpha-smooth muscle actin(α-SMA) in cutaneous and pulmonary tissues was performed to evaluatemyofibroblast differentiation. Lung and skin concentrations of vascularendothelial growth factor (VEGF), extracellular signal-related kinase (ERK),rat sarcoma protein (Ras), Ras homolog gene family (Rho), and transforminggrowth factor (TGF) β were analyzed by Western blot. Injections of HOCl induced cutaneous and lung fibrosis in BALB/c mice. PTUtreatment prevented both dermal and pulmonary fibrosis. Myofibroblastdifferentiation was also inhibited by PTU in the skin and lung. The increasein cutaneous and pulmonary expression of VEGF, ERK, Ras, and Rho in micetreated with HOCl was significantly prevented in mice co-administered////with PTU. PTU, probably through its direct effect on reactive oxygen species orindirectly through thyroid function inhibition, prevents the development ofcutaneous and pulmonary fibrosis by blocking the activation of the Ras-ERKpathway in the oxidant-stress animal model of SSc.

– OBJECTIVE: We developed a standardized technique for ultrasound guided intra-articular injection of the hip joint with the purpose of extending routine intra-articular injection of hyaluronans and steroids to the hip, as commonly used in the knee. In this article we report the safety of this technique in an extended series of patients. PATIENTS AND METHODS: Patients were injected supine with an anterosuperior approach under ultrasound guidance. The Us probe is applied with a target device for biopsy. RESULTS: The standardised technique was used to inject 1906 patients with 4002 injections of hyaluronan products over a four-year period. The treatment was well tolerated with few, and exclusively local, side effects. CONCLUSIONS: The administration of hyaluronans under ultrasound-guided intra-articular injection is a safe technique for treatment of rheumatic diseases of the hip.

OBJECTIVE: The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc). METHODOLOGY: Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures. RESULTS: bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p

Background Systemic sclerosis (SSc) is an autoimmune chronic disease characterized by diffuse fibrosis involving several organs, including heart. Aim of our study was to analyze left ventricular (LV) myocardial deformation, by use of 2D strain, in asymptomatic SSc patients with normal LV ejection fraction. Methods We enrolled 29 SSc patients (28 female, 65±4 years) and 30 controls (23 female, 64±2 years). Echocardiographic study with tissue Doppler imaging (TDI) and 2D strain analysis was performed; moreover, patients were submitted to a two-year follow-up for the occurrence of cardiovascular events. Results Standard echocardiographic parameters and TDI velocities were comparable between groups. LV longitudinal (LS) and circumferential (CS) strains were lower in patients than in controls (−13.1±4.8 vs −22.6±4.1, p < 0.001; -15.3±6.2 vs −20.4±5.6, p = 0.001), whereas radial strain (RS) was comparable between groups; moreover, a significant correlation of LS and CS with serum levels of Scl-70 antibodies was found (r = 0.74, p = 0.001; r = 0.53, p = 0.025). In addition, patients with cardiovascular events during follow-up showed a greater impairment of LS and CS (−10.3±2.5 vs −14.4±4.1, p = 0.015; -14.2±3.1 vs −20.1±1.6, p = 0.048) and higher values of Scl-70 antibodies serum levels (p = 0.047). Conclusion The impairment of LV function, often subclinical, worsens prognosis of SSc patients, leading to increased risk of cardiovascular complications. 2D strain, allowing the early detection of LV abnormalities and the identification of patients at greater cardiovascular risk, may be a useful tool in order to provide a more accurate management of SSc patients.

Objective. Therapeutic approach of osteoarthritis (OA) still represents a challenge in clinical practice. The aim of the study is to assess the efficacy of far infrared (FIR) emitting plaster in the treatment of knee OA. Design. This is a randomized, single-blind, placebo-controlled, parallel group with equal randomization (1:1), clinical trial. Patients affected by knee OA were randomly allocated to 1 of 2 treatment groups, either placebo plaster or far infrared emitting plaster. Primary endpoint was to assess pain improvement from baseline to 1 months posttreatment in the visual analogue score (VAS). Secondary end point was to evaluate pain score after 1 week of treatment and to compare ultrasonographic findings after 1 month of treatment. Results. Each group comprised 30 (in the FIR group) and 30 (in the placebo group) completers. VAS scores of the placebo and the FIR group were significantly lower at 1 week post-treatment (95% confidence interval CI = -1.14 to 0.31; PConclusions. Far infrared emitting plaster could be considered an effective non-pharmacological choice for the therapeutic management of knee OA.