Endocan and Circulating Progenitor Cells in Women with Systemic Sclerosis: Association with Inflammation and Pulmonary Hypertension.

BACKGROUND: Systemic sclerosis (SSc) is characterized by early vasculopathy and fibrosis in the skin, lungs, and other tissues. Vascular manifestations of SSc include Raynaud's phenomenon, digital ulcers, and pulmonary artery hypertension (PAH). PAH is the second most common cause of mortality in SSc. Circulating CD34+ cells associated with cardiovascular health status in several conditions, including chronic immune-inflammatory disease. CD34+ cell numbers have been found inconstantly reduced in SSc. Endocan, a proteoglycan expressed by endothelial cells, was recently suggested as a marker of vascular stress. We tested the relationships among CD34+ cells, endocan, inflammatory markers, vitamin D levels, and clinical parameters in SSc patients with PAH. METHODS: Standard echocardiography was performed. Vitamin D levels, CD34+ cells, inflammatory markers, endocan plasma levels were determined in 36 female SSc patients (24 diffuse/12 limited) and 36 matched controls (HC). RESULTS: We found no difference in CD34+ and vitamin D levels in SSc as compared to controls; ESR, CRP, fibrinogen, endocan, sPAP were higher in SSc with respect to controls. We found a correlation between endocan and: CD34+ cells (r: -0.540, p = 0.002), pulmonary arterial pressure (sPAP) (r: 0.565, p < 0.001), tricuspid annular plane excursion (TAPSE) (r: -0.311, p < 0.01), and E/A ratio (r: -0.487, p < 0.001), but not with ejection fraction (r: -0.057, p = 0.785) in SSc. CD34+ cells correlate with fibrinogen (r: -0.619, p < 0.001), sPAP (r: -0.404, p = 0.011), E/A (r: 0.470, p < 0.005 in SSc. CONCLUSION: CD34+ cell number was significantly correlated with endocan levels and with sPAP in SSc; endocan and CD34+ progenitor cells might be suggested as a potential marker of disease status.

The PREdictor of MAlnutrition in Systemic Sclerosis (PREMASS) Score: A Combined Index to Predict 12 Months Onset of Malnutrition in Systemic Sclerosis.

Objective: Malnutrition is a severe complication in Systemic Sclerosis (SSc) and it is associated with significant mortality. Notwithstanding, there is no defined screening or clinical pathway for patients, which is hampering effective management and limiting the opportunity for early intervention. Here we aim to identify a combined index predictive of malnutrition at 12 months using clinical data and specific serum adipokines. Methods: This was an international, multicentre observational study involving 159 SSc patients in two independent discovery (n = 98) and validation (n = 61) cohorts. Besides routine clinical and serum data at baseline and 12 months, Malnutrition Universal Screening Tool (MUST) score and serum concentration of leptin and adiponectin were measured for each participant at baseline. The endpoint of malnutrition was defined according to European Society of Clinical Nutrition and Metabolism (ESPEN) recommendation. Significant parameters from univariate analysis were tested in logistic regression analysis to identify the predictive index of malnutrition in the derivation cohort. Results: The onset of malnutrition at 12 months correlated with adiponectin, leptin and their ratio (A/L), MUST, clinical subset, disease duration, Scl70 and Forced Vital Capaciy (FVC). Logistic regression analysis defined the formula: -2.13 + (A/L*0.45) + (Scl70*0.28) as the best PREdictor of MAlnutrition in SSc (PREMASS) (AUC = 0.96; 95% CI 0.93, 0.99). PREMASS < -1.46 had a positive predictive value (PPV) > 62% and negative predictive value (NPV) > 97% for malnutrition at 12 months. Conclusion: PREMASS is a feasible index which has shown very good performance in two independent cohorts for predicting malnutrition at 12 months in SSc. The implementation of PREMASS could aid both in clinical management and clinical trial stratification/enrichment to target malnutrition in SSc.

Controlled-release pregabalin in the treatment of fibromyalgia.

INTRODUCTION: Fibromyalgia (FM) is a chronic disorder whose symptoms of musculo-skeletal pain, fatigue, sleep disturbances, and cognitive impairment pervade the personal, occupational, and social aspects of a patient's life. Together with the antidepressants duloxetine and milnacipran, the anticonvulsant pregabalin (PGB) is one of the three drugs approved by the Food and Drug Administration for the treatment of FM. The aim of this narrative review is to summarize the data relating to the efficacy and safety of the controlled-release formulation of PGB (PGB-CR) in patients with FM. Areas covered: Efforts by the pharmaceutical industry have led to the introduction of new formulations of already approved drugs to enhance treatment convenience and adherence. Expert opinion: Although there are no published studies specifically comparing PGB-CR and PGB-IR formulations in FM patients, the efficacy and safety profiles of PGB-CR seem to be similar to those of the IR formulation, and the convenience of once-daily dosing potentially enhances patient compliance. However, the amount of evidence is not sufficient to draw any definite conclusions, and further studies of larger patient samples are needed.

Association between cortisol levels and pain threshold in systemic sclerosis and major depression.

Pain perception and threshold show complex interactions with the inflammatory, psychiatric and neuroendocrine stimuli. This study aims to test whether lower serum cortisol levels are associated with lower pain thresholds and higher degree of depression in systemic sclerosis (SSc) and major depression with atypical features (MD-AF) patients compared to controls. 180 female subjects (SSc = 60, MD-AF = 60, healthy controls = 60) participated in this observational, cross-sectional, parallel group study. Pressure pain threshold (PPT) was assessed in three anatomical sites: nail bed (NB), metacarpophalangeal joint (MCP) and quadriceps muscle (QDR). Depressive symptoms were evaluated using the Beck Depression Inventory (BDI) scale and morning serum cortisol levels were collected. In SSc patients, quality of life was measured through the Health Assessment Questionnaire (HAQ-DI) and the scleroderma-specific visual analogue scales (scleroderma-VAS). Lower PPT scores (NB 4.42 ± 1.6; MCP 4.66 ± 1.4; QDR 4.79 ± 1.5) were observed in SSc patients compared to both MD-AF (NB 7.33 ± 2.2; MCP 6.01 ± 1.9; QDR 6.31 ± 1.6; p < 0.005) and controls (NB 9.57 ± 2; MCP 7.9 ± 2.1 and QDR 8.43 ± 2.1; p < 0.0001), while MD-AF patients had lower PPT scores compared to controls (p < 0.0001). SSc patients had also lower serum cortisol levels compared to MD-AF patients (8.78 vs 13.6 µg/dl; p < 0.05). A direct correlation was observed between serum cortisol and PPT scores both in SSc (r 2 for NB 0.29; for MCP 0.25; for QDR 0.27) and in MD-AF (r 2 for NB 0.34; for MCP 0.25; for QDR 0.47; p < 0.05), while depressive symptoms negatively correlated with serum cortisol (r 2 for NB 0.34; for MCP 0.17; for QDR 0.15) and in MD-AF (r 2 for NB 0.19; for MCP 0.31; for QDR 0.30; p < 0.05). Among SSc patients, those with serum cortisol levels below the normal range (n = 16) had higher BDI scores (15, 6-21 vs 9, 2-15; p < 0.005), lower PPTs (NB 4 ± 1.4 vs 4.9 ± 0.9; MCP 4.1 ± 0.8 vs 4.8 ± 0.9; QDR 4.1 ± 1.2 vs 5 ± 0.9; p < 0.005) and higher HAQ-DI (1.25, 0.25-2 vs 0.75, 0-1.25; p < 0.05) and scleroderma-VAS scores (VAS overall severity 7, 5.5-9.5 vs 4.5, 2.5-6; p < 0.05). The effect of cortisol serum levels upon pain mechanism, in chronic inflammatory conditions warrants longitudinal studies to detect treatable variations in pain thresholds, depressive symptoms and to improve quality of life.

Mastocytosis and systemic sclerosis: a clinical association.

BACKGROUND: Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vascular alterations and autoimmune activation leading to widespread organ fibrosis. At the early stage of disease when organ involvement and extent of disease are emerging, mast cells may have some role, as implied by both symptoms and histologic evidence. CASE PRESENTATION: A female patient diagnosed with cutaneous mastocytosis experienced the onset of systemic sclerosis after 15 years followed by the switch of mastocytosis to the systemic phenotype. A literature review on the evidences related to mast-cells activation in systemic sclerosis is presented below. CONCLUSIONS: For clinicians, more attention must be paid to the potential association between systemic sclerosis and cancer. This case suggests that a proliferative disease in the mast cell compartment-though representing a rare association-may not be completely unexpected in SSc and perhaps excess mast cell activity can serve a pathogenic role in promoting fibrotic disease.

Pulsed electromagnetic fields in knee osteoarthritis: a double blind, placebo-controlled, randomized clinical trial.

OBJECTIVES: This trial aimed to test the effectiveness of a wearable pulsed electromagnetic fields (PEMF) device in the management of pain in knee OA patients. METHODS: In this randomized [with equal randomization (1:1)], double-blind, placebo-controlled clinical trial, patients with radiographic evidence of knee OA and persistent pain higher than 40 mm on the visual analog scale (VAS) were recruited. The trial consisted of 12 h daily treatment for 1 month in 60 knee OA patients. The primary outcome measure was the reduction in pain intensity, assessed through VAS and WOMAC scores. Secondary outcomes included quality of life assessment through the 36-item Medical Outcomes Study Short-Form version 2 (SF-36 v2), pressure pain threshold (PPT) and changes in intake of NSAIDs/analgesics. RESULTS: Sixty-six patients were included, and 60 completed the study. After 1 month, PEMF induced a significant reduction in VAS pain and WOMAC scores compared with placebo. Additionally, pain tolerance, as expressed by PPT changes, and physical health improved in PEMF-treated patients. A mean treatment effect of -0.73 (95% CI - 1.24 to - 0.19) was seen in VAS score, while the effect size was -0.34 (95% CI - 0.85 to 0.17) for WOMAC score. Twenty-six per cent of patients in the PEMF group stopped NSAID/analgesic therapy. No adverse events were detected. CONCLUSION: These results suggest that PEMF therapy is effective for pain management in knee OA patients and also affects pain threshold and physical functioning. Future larger studies, including head-to-head studies comparing PEMF therapy with standard pharmacological approaches in OA, are warranted. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01877278.