Low-energy Pulsed Electromagnetic Field Therapy Reduces Pain in Fibromyalgia: A Randomized Single-blind Controlled Pilot Study.

Objectives: Fibromyalgia symptoms have a significant impact on the quality of life and respond poorly to medications. It has been hypothesized that the use of low-energy pulsed electromagnetic field (PEMF) induces neuroprotective effects that may interfere with pain perception. We explored the efficacy of PEMF in patients affected by fibromyalgia. Methods: Twenty-one females (median age 59 years, interquartile range [IQR] 16.5) affected by fibromyalgia were randomized to receive pulsed electromagnetic field-triple energy pain treatment (PEMF-TEPT) or placebo at T0 and at 4 weeks and 8 weeks. Fibromyalgia impact questionnaire (FIQ), widespread pain index (WPI), visual analog score (VAS) pain, symptom severity (SS) scale, and short form 36 (SF-36) health survey questionnaire have been evaluated. Results: Patients in the PEMF-TEPT group had a significantly higher reduction of WPI compared to placebo (mean difference -12.90 ± standard deviation [SD] 5.32 vs. -1.91 ± 4.55, difference in difference [DD] of -10.99; P < 0.001), of SS score (-4.10 ± 4.85 vs. -2.00 ± 2.32; DD = -2.1; P < 0.05), of VAS pain (-48 ± 30.75 vs. -16.82 ± 23.69; DD = -31.18; P < 0.01). They also reported a higher improvement of FIQ and SF-36, albeit not reaching statistical significance. Conclusion: In our pilot controlled study, PEMF-TEPT appeared to be safe and improved fibromyalgia symptoms.

Clinical and echocardiographic correlations of exercise-induced pulmonary hypertension in systemic sclerosis: a multicenter study.

BACKGROUND: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation. AIM: The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc. METHODS: We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively. RESULTS: Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR. CONCLUSIONS: Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc.

A proposal of simple calculation (ERI calculator) to predict the early response to TNF-α blockers therapy in rheumatoid arthritis.

Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-α blocking agents. The formulation and definition of an early indicator of patient's reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.

Incident comorbidity among patients with rheumatoid arthritis treated or not with low-dose glucocorticoids: a retrospective study.

OBJECTIVE: To assess the prevalence of comorbidity in a cohort of patients with rheumatoid arthritis (RA), treated or not with low-dose glucocorticoids (GC) and who have been followed for at least 10 years. METHODS: This was a retrospective study by review of medical records. RESULTS: We identified 365 patients: 297 (81.3%) were GC users (4-6 mg methylprednisolone daily) and 68 (18.7%) were nonusers. We found that fragility fractures occurred in 18.2% of GC users and in 6.0% of GC nonusers (p < 0.02); arterial hypertension in 32.3% of GC users and in 10.4% of GC nonusers (p < 0.0005); acute myocardial infarction in 13.1% of GC users and in 1.5% of the nonusers (p < 0.01). Prevalence of diabetes mellitus, cataract, and infections was comparable. We divided GC users into groups of different duration of GC therapy: < 2, 2-5, and > 5 years; the mean duration of GC treatment was 1.3 ± 0.5, 3.6 ± 1.1, and 12.1 ± 5.1 years, respectively. GC treatment for > 5 years was associated with significantly higher prevalence of fragility fractures (26.6%; p < 0.001 vs the other groups), arterial hypertension (36.7%; p < 0.0002 vs nonusers and GC users < 2 years), myocardial infarction (16.1%; p < 0.01 vs nonusers), and infections (9.7%; p < 0.005 vs the other groups). GC treatment for 2-5 years was associated with a significantly higher prevalence of arterial hypertension (30.0%; p < 0.01) compared to nonusers. CONCLUSION: Patients with RA treated with low-dose GC compared to patients never treated with GC show a higher prevalence of fractures, arterial hypertension, myocardial infarction, and serious infections, especially after 5 years of GC treatment. The high prevalence of myocardial infarction and fractures in patients with RA suggests that a more accurate identification of risk factors and prevention measures should be adopted when longterm GC treatment is needed.

Diagnosis and referral of rheumatoid arthritis by primary care physician: results of a pilot study on the city of Pisa, Italy.

The aims of the present study were to evaluate, in the city of Pisa: (1) the prevalence of rheumatoid arthritis; (2) the reliability of the prevalence estimated by primary care physicians, using the rheumatologist's diagnosis as the "gold standard" and (3) the economic impact of the disease. The Tuscany registry of primary care physicians constituted the framework from which a sample of subjects was selected. The rheumatoid arthritis (RA) subjects >18 years followed by each primary care physician constituted the population studied. Each general practitioner (GP) was asked to fill out a questionnaire regarding their patients affected by RA and to send it to the tertiary rheumatologic centre, where the diagnosis was confirmed/discarded, the clinical and epidemiological data were collected in a standardized form and a number of data for the estimation of costs were gathered. The estimated prevalence of RA was 5.1 per thousand (CI, 4.4-5.7). The reliability of general practitioners in the diagnosis of rheumatoid arthritis was on the whole 69%. However, when an analysis of every physician was carried out, a high degree of heterogeneity in the prevalence of RA per physician was found. Overall, the mean annual cost per patient with RA was estimated at about 5,878 euro (euro; median, 6,434 euro; inter quartile range, 669-7,052 euro), with a high variability mainly dependent on the degree of patient disability. More than 90% of the overall annual cost per patient was due to the medical and non-medical direct components of costs. The prevalence of RA in Tuscany seems highly comparable with similar prevalence studies in Italy. The annual cost per patient with RA was highly variable and strictly dependent on the level of disability. More than 90% of the overall cost was due to the direct burden of costs.

Ultrasound lung comets in systemic sclerosis: a chest sonography hallmark of pulmonary interstitial fibrosis.

OBJECTIVE: To assess the correlation between ultrasound lung comets (ULCs, a recently described echographic sign of interstitial lung fibrosis) and the current undisputed gold-standard high-resolution CT (HRCT) to detect pulmonary fibrosis in patients with SSc. METHODS: We enrolled 33 consecutive SSc patients (mean age 54 +/- 13 years, 30 females) in the Rheumatology Clinic of the University of Pisa. We assessed ULCs and chest HRCT within 1 week independently in all the patients. ULC score was obtained by summing the number of lung comets on the anterior and posterior chest. Pulmonary fibrosis was quantified by HRCT with a previously described 30-point Warrick score. RESULTS: Presence of ULCs (defined as a total number more than 10) was observed in 17 (51%) SSc patients. Mean ULC score was 37 +/- 50, higher in the diffuse than in the limited form (73 +/- 66 vs 21 +/- 35; P < 0.05). A significant positive linear correlation was found between ULCs and Warrick scores (r = 0.72; P < 0.001). CONCLUSIONS: ULCs are often found in SSc, are more frequent in the diffuse than the limited form and are reasonably well correlated with HRCT-derived assessment of lung fibrosis. They represent a simple, bedside, radiation-free hallmark of pulmonary fibrosis of potential diagnostic and prognostic value.

Cell-free DNA in the plasma of patients with systemic sclerosis.

The aim of the present study was to evaluate the concentration of cell-free DNA (cf-DNA) in the plasma of patients with systemic sclerosis (SSc) and to examine the correlation of cf-DNA with clinical variables of the disease. The study population consisted of 122 SSc patients and 16 healthy controls. Epidemiological and clinical data were collected by direct assessment. The beta-globin gene was used to determine the total amount of DNA in the plasma by real-time quantitative PCR analysis. cf-DNA was found in all patients (mean concentration 1,420.7 copies/ml) and controls (mean concentration 1,462.5), with no significant difference. In SSc patients, no correlation was found between cf-DNA and the type of organ involvement, but patients with active disease presented significantly higher cf-DNA concentrations than those with inactive disease (p < 0.05). Our data suggest that cf-DNA could provide a useful biomarker for the assessment of disease activity in SSc patients.

Association of psoriasin (S100A7) with clinical manifestations of systemic sclerosis: is its presence in whole saliva a potential predictor of pulmonary involvement?

OBJECTIVE: To evaluate psoriasin (S100A7) expression in whole saliva (WS) of patients with diffuse systemic sclerosis (dSSc) and limited SSc (lSSc), and to correlate its presence with the different clinical manifestations of the disease. METHODS: Forty-four patients with limited or diffuse SSc were enrolled for study. WS proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and psoriasin was identified by Western blot analysis using a specific polyclonal antibody. Patients with other rheumatic diseases with and without lung involvement were enrolled as pathological controls. Statistical analysis was performed to correlate each clinical manifestation with the presence of psoriasin. RESULTS: Three bands of 12, 24, and 50 kDa corresponding to monomeric and dimeric/multimeric forms of psoriasin were evidenced by immunoblot analysis in WS of 31 out of 44 patients with SSc (70.4%). In the other 13 WS samples, the 12 kDa band was totally absent, while the dimeric and multimeric bands were expressed at optical intensity (OD) levels comparable to the other samples. From a clinical point of view, the presence of 12 kDa monomeric psoriasin was significantly associated with SSc pulmonary involvement and with anti-Scl-70 antibody positivity. No control showed the psoriasin 12 kDa band. CONCLUSION: Our results identified salivary 12 kDa psoriasin as a potential predictor of pulmonary involvement in SSc. Thus, a psoriasin assay might be considered as a rapid, noninvasive, useful salivary biomarker for the detection of pulmonary involvement in SSc.

Antipolymer antibody in Italian fibromyalgic patients.

The objectives of the present study were to evaluate the presence of antipolymer antibody (APA) seropositivity in 285 Italian patients affected by primary fibromyalgia (FM) and to verify whether APA levels correlate with disease severity and with cytokine levels.APA levels were determined on serum samples by an indirect ELISA kit that detects IgG APA. Cytokines (IL-1, IL-6, IL-8, IL-10 and TNFalpha) were measured by ELISA in plasma. The impact of FM on the quality of life was estimated using the Fibromyalgia Impact Questionnaire, while pain severity was evaluated using a visual analogic scale. Patients were also characterized by the presence of tiredness, stiffness, nonrestorative sleep, anxiety, depression, tension headache, irritable bowel syndrome, temporomandibular dysfunction and Raynaud's phenomena. Using a cut-off value of 30 U, APA-positive values were detected in 60 FM patients (21.05%) and in 15 healthy control individuals (15.00%) without significant differences among their levels or the percentage of seropositivity. FM patients with moderate and severe symptoms had slightly higher APA levels with respect to patients with mild symptoms. APA-seropositive patients exhibited significant correlations between APA levels and the Fibromyalgia Impact Questionnaire estimate (P = 0.042), tiredness (P = 0.003) and IL-1 levels (P = 0.0072). In conclusion, APA cannot be considered a marker of disease in Italian FM patients. The presence of APA, however, might permit the identification of a subset of FM patients with more severe symptoms and of patients who may respond differently to different therapeutic strategies.