Ugo Fiocco

Section of Rheumatology · Arcella Private Medical Center Via Tiziano Aspetti, 106, 35133 – Padova – Italy

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical tra...

Contrast-enhanced ultrasound (CEUS) is a sensitive imaging technique to evaluate blood perfusion and tissue vascularity, whose quantification can assist in characterizing different perfusion patterns, e.g. in cancer or in arthritis. The perfusion parameters are estimated by fitting non-linear parametric models to experimental data, usually through...

Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. Real world data on efficacy and safety of TNF-α blockers in the elderly with PsA are lacking. The aim of this study was to evaluate the effectiveness, through the achievement of minimal disease activity (MDA), drug discontinuation rate, and safety...

The onset and progression of immune-mediated inflammatory arthritis, such as rheumatoid arthritis and spondyloarthritis, are linked to the IL23-IL17 immune axis, so that many therapeutic strategies aim at modulating this pathway. However, there is so far no possibility of an in vivo direct monitoring, without a biopsy, of the specific T cells invol...

Contrast Enhanced Ultrasound (CEUS) is a sensitive imaging technique to assess tissue vascularity, that can be useful in the quantification of different perfusion patterns. This can be particularly important in the early detection and staging of arthritis. In a recent study we have shown that a Gamma-variate can accurately quantify synovial perfusi...

Contrast Enhanced Ultrasound (CEUS) is a sensitive imaging technique to assess tissue vascularity, that can be useful in the quantification of different perfusion patterns. This can be particularly important in the early detection and staging of arthritis. In a recent study we have shown that a Gamma-variate can accurately quantify synovial perfusi...

To develop quantitative imaging biomarkers of synovial tissue perfusion by pixel-based contrast-enhanced ultrasound (CEUS), we studied the relationship between CEUS synovial vascular perfusion and the frequencies of pathogenic T helper (Th)-17 cells in psoriatic arthritis (PsA) joints. Eight consecutive patients with PsA were enrolled in this study...

Contrast Enhanced Ultrasound (CEUS) is a sensitive imaging technique to assess tissue vascularity and it can be particularly useful in early detection and grading of arthritis. In a recent study we have shown that a Gamma-variate can accurately quantify synovial perfusion and it is flexible enough to describe many heterogeneous patterns. However, i...

Objectives: To evaluate the effects on disease activity of seasonal influenza vaccination with adjuvant in psoriatic arthritis (PsA) patients in stable disease activity on anti-TNF-α drugs as compared to not vaccinated PsA patients adequately matched. Methods: An observational study was conducted on a cohort of PsA patients in stable disease act...

Arthritis encompasses a heterogeneous group of diseases characterised by inflammation that leads not only to joint damage, bone erosion, severe pain and disability, but also affects other organs of the body, resulting in increased morbidity and mortality. Although the mechanisms underlying the pathogenesis of joint diseases are for the most part un...

We assessed signaling protein mapping in total T cells, to analyze the proportions of T regulatory (Treg) and TCD4+ effector (Teff) cell phenotypes, and the respective interleukin 6R alpha (IL-6R alpha) expression in the inflammatory microenvironment of synovial fluid (SF) of patients with sustained psoriatic arthritis (PsA). Our approach was to me...

Inflammatory rheumatic diseases are the leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity, and increased mortality. The standard for diagnosing and differentiating arthritis is based on clinical examination, laboratory exams, and imaging findings, such as synovitis, bone edema, o...

The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orpha...

The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transd...

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory condition involving the spine, enthesis and peripheral joints, which is associated with psoriasis. PsA therapy varies from use of NSAIDs to disease-modifying anti-rheumatic agents (DMARDs). However, their use can represent a limitation in patients with concomitant hepatitis C virus...

The aim of the study was to evaluate the influence of metabolic syndrome (MetS) on achieving minimal disease activity (MDA) in psoriatic arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)-α with a follow-up period of 24 months. A cohort of PsA patients was assessed at the University Federico II of Naples and at University of Pad...

Background Crystal deposition in joints leads to leukocyte recruitment and a massive release of various inflammatory mediators, in particular cytokines and chemokines. These events are well reproduced by in vitro models in which the inflammatory response has been studied in different cell type. However, it has not yet determined the exact contribut...

Objectives To analyse a panel of synovial fluid (SF) and synovial tissue (ST) biological markers expression at single joint level to find candidate biomarkers in resistant peripheral spondyloarthritis (SpA). Methods Twenty seven resistant SpA patients with knee joint synovitis, included in an Intra-articular (IA) TNF alpha blocking open-label study...

Looking to the sustained psoriatic arthritis (PsA) joint as a model of local human inflammation, this study was designed to assess the T lymphocyte signal transduction pathways potentially involved in this chronic immune-mediated inflammatory process, as characterized by direct ex vivo analysis of T helper (Th)-17 T effector (Teff) cell phenotypes...

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy an...

Psoriatic arthritis (PsA) is a chronic inflammatory condition, characterized by an excess of metabolic disorders. Metabolic syndrome (MetS) is a cluster of classic cardiovascular risk factors, due to an imbalance between pro- and anti-inflammatory adipokines. Tumor necrosis factor (TNF)-α is a pro-inflammatory adipocytokine mainly produced by monoc...

Although osteoarthritis (OA) is defined as a cartilage disease, synovitis involving mononuclear cell infiltration and overexpression of proinflammatory mediators is common in early and late OA. Calcium crystals deposition is thought to be a factor that likely contributes to synovial inflammation. In recent years, significant interest has emerged in...

Objectifs Cette étude réalisée en ouvert est basée sur une approche translationnelle dans le but de détecter les changements cliniques, à l’imagerie et des biomarqueurs synoviaux dans le liquide synovial (LS) et le tissu synovial (TS) dans la spondyloarthropathie périphérique (SpA) après l’inhibition intra-articulaire (IA) du tumor necrosis factor...

Objectives: To provide a survey of disease activity in patients treated with standard care in Italian clinical practice. Methods: This was an observational prospective cohort study in patients with early, aggressive rheumatoid arthritis (RA; duration ≤2 years but ≥6 weeks; DAS28 >3.2) naïve to anti-tumour necrosis factor (TNF) therapy who were t...

Objectives: Several single nucleotide polymorphisms (SNPs) have been associated with rheumatoid arthritis (RA) such as peptidylarginine deiminase-4 (PADI4), osteopontin (OPN), and perforin (PRF1) genes. Thus, we aimed at analysing the influence of eight SNPs in these candidate genes on RA susceptibility and their association with laboratory and cl...

We would like to add some comments with regard to our own experimental data concerning the immunomodulatory effect of plasma on calcium crystal-induced inflammation to findings outlined by Sohn and colleagues. Our results show that healthy human plasma in THP1 cells is able to enhance the release of IL-1beta and IL-8 in a dose dependent manner but...

Objectives: This open-label study is based on a translational approach with the aim of detecting changes in the clinical condition as well as in imaging and synovial biological markers in both synovial fluid (SF) and synovial tissue (ST) in peripheral spondyloarthritis (SpA) patients following intra-articular (IA) blockade of TNF-α by serial etane...

To find candidate biomarkers of psoriatic arthritis (PsA). A panel of synovial fluid (SF) and synovial tissue (ST) biomarkers was analyzed in patients with resistant peripheral PsA, in relation to clinical and imaging outcomes of synovitis response following serial intraarticular (IA) etanercept injections (12.5 mg). Fourteen PsA patients with resi...

Rheumatoid arthritis (RA) is a chronic multisystemic autoimmune disease, with an unclear etiopathogenesis. Its early diagnosis and activity assessment are essential to adjust the proper therapy. Among the different imaging techniques, ultrasonography (US) allows direct visualization of early inflammatory joint changes as synovitis, being also rapid...

To assess synovial microvascularity in finger joints with rheumatoid arthritis (RA) by contrast-enhanced ultrasound (CEUS), distinguishing between cases of active disease and those in remission; to standardize the technique for software analysis. Fifty-two finger joints of RA patients (26 with active disease and 26 in remission) were immersed in wa...

Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgical synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treatments. To determine the safety and efficacy of intra-articular (IA) TNF-αa blockade with etanercept (ETN), before extend...

We evaluated both the efficacy and safety of anakinra in daily routine rheumatoid arthritis clinical practice. We studied 60 cases, including patients with previous anti-TNFalpha exposure, treated with anakinra (100 mg/daily s.c.) in combination with methotrexate (7.5-10 mg/week i.m.) or leflunomide (20 mg/die) in a two year observational study. Ef...

We evaluated the induction and clinical significance of ANA, anti-dsDNA and anti-ENA during infliximab therapy in patients with Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS). We tested sera from 30 RA and 30 AS patients before and during treatment with infliximab. ANA and antidsDNA were determined by indirect immunofluorescence and anti-...

Interleukin 1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1 inhibitor, acting as a "receptor antagonist", which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumato...

To delineate the molecular mechanisms underlying the process of the diffuse-type giant cell tumours, also called pigmented villonodular synovitis, a rare, aggressive condition of the synovium, the knee synovial tissue expression of colony-stimulating factor-1 gene, as detected by real-time polymerase chain reaction, was compared between patients af...

This study aims to provide a description of real life treatment patterns of biologic anti-TNF in 23 Italian Rheumatology centers. This was an observational, multicenter, retrospective study. Patients >18 years of age, diagnosed with rheumatoid arthritis and treated with the first biologic anti-TNF agent between the 1st July 2002 to the 31st March 2...

Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression. The p...

The purpose of this study was the evaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA). Systemic and local disease activity indexes (disease activity score...

Inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), are leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high co-morbidity and increased mortality; RA involves indirect expenses secondary to disability, loss of productivity and early retirement. The gold-standard for diagnosing R...

To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy. Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2-3 g/...

Associations between rheumatoid arthritis (RA) susceptibility and polymorphism in multiple immunoregulatory genes suggest a role of altered T cell function in the disease. The growing relevance of the oxidative stress in RA synovitis, which results in a number of T cell signalling abnormalities, is reinforced by the demonstration of a direct NO ind...

The classical definition of psoriatic arthritis (PsA) as an inflammatory arthritis associated with psoriasis reflects only in part the large spectrum of musculoskeletal disorders found in patients with psoriasis. In particular, enthesopathy, dactilytis, osteitis and axial involvement are frequently neglected and probably account for the unsatisfact...

Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgical synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treatments. To determine the safety and efficacy of intra-articular (IA) TNFalpha blockade with etanercept (ETN), before exte...

To compare the efficacy and safety of etanercept and sulfasalazine, alone and in combination, in patients with active rheumatoid arthritis despite sulfasalazine treatment. A double-blind, randomised study in adult patients with active rheumatoid arthritis despite stable sulfasalazine (2-3 g/day) treatment. The primary end point was a 20% response b...

Gli autoanticorpi antinucleo, anti-dsDNA anti-ENA nei pazienti con artrite reumatoide o spondilite anchilosante in trattamento con infliximab Antinuclear, anti-dsDNA and anti-ENA antibodies in patients affected with rheumatoid arthritis or ankylosing spondylitis during treatement with infliximab nociti e cellule endoteliali. Questa citochina ha un...

Expression of CXCR3-targeting chemokines have been demonstrated in several diseases, suggesting a critical role for CXCR3 in recruiting activated T cells to sites of immune-mediated inflammation. Sjögren's syndrome (SS) is an autoimmune disease characterized by a mononuclear cell infiltrate of activated T cells around the duct in the salivary gland...

To determine the effect of tumour necrosis factor alpha (TNFalpha) blockade with etanercept in refractory knee joint synovitis (KJS) in rheumatoid and psoriatic arthritis, by local and systemic disease activity assessment and combined grey scale and power Doppler ultrasonographic monitoring. 27 knees affected by rheumatoid KJS (n = 12) and psoriati...

The commercially available inhibitors of TNF are constituted by two classes of molecules: the soluble receptors (Etanercept: Amgen Inc. Wyeth) and the monoclonal antibodies (Adalimumab: Abbott Laboratories and Infliximab: Centocor, Inc.). The differences in their molecular structure, mechanism of action, pharmacokinetics (PK) and pharmacodynamics (...

To evaluate the contribution of continuous mode contrast-enhanced harmonic ultrasonography (CE-HUS) with a second-generation contrast agent to the characterization of superficial lymphadenopathies with respect to conventional ultrasonographic techniques (B-mode and power Doppler). Fifty-six lymph nodes from 45 patients were studied both by conventi...

Different animal studies show that several proinflammatory cytokines are essential for natural resistance to specific infections, particularly versus intracellular organisms. However, uncontrolled overproduction of some proinflammatory cytokines, in diseases such as rheumatoid arthritis, can be just as dangerous to the host as the absence of the sa...

To evaluate the reliability of contrast-unenhanced power Doppler (CUPD) and contrast-enhanced power Doppler (CEPD) ultrasound (US) assessment of synovial vascularity of knee joint synovitis by prospective comparison with the "gold standard," arthroscopy. A total of 18 knees of 17 patients with refractory rheumatoid and psoriatic knee joint synoviti...

To evaluate the diagnostic utility of standard arthroscopy supported by a computerized image analysis system; and to examine and quantify the macroscopic appearance of blood vessels in selected anatomical areas, comparing 2 groups of patients with PsA and RA with refractory knee joint synovitis (KJS) for vascular marking (VM) features and VM scores...

A long-term prospective study was performed to evaluate the safety and long-term outcome of surgical arthroscopy (AS) for persistent rheumatoid (RA) and psoriatic (PsA) knee joint synovitis (KJS). Local signs of joint inflammation (tenderness, swelling, "ballottement') and range of motion (ROM) were scored and the sum, taken as a global outcome mea...

The potential role of sonography in evaluating the response to therapy of persistent knee joint synovitis (KJS) was assessed in a longitudinal study in pre-and post-arthroscopic (AS) synovectomy in rheumatoid and psoriatic patients. At entry to the study ultrasound (US) detection of synovial proliferation was compared with arthroscopic visualizatio...

The objective of this study was to verify the accuracy of ultrasonography in assessing the topography, morphology, and extent of synovial proliferation in rheumatoid and psoriatic knee joint synovitis. Findings were compared to those obtained using prospective arthroscopy as the gold standard; in addition, topographically defined sonographic findin...

The differential expression of several accessory/activation molecules (CD26, CD29, CD45RA, CD25, MLR4, HLA-DR) on peripheral blood CD4+ and CD8+ T lymphocytes in patients with scleroderma was compared with that in controls and patients with other connective systemic diseases to look for evidence of the involvement of T cells in the disease process...

To investigate the possible immunomodulatory mechanism of D-penicillamine in Scleroderma (Scl), we analysed the surface phenotype of circulating T lymphocytes in 17 Scl patients, 6 of these studied before and after D-penicillamine treatment, 8 only before and 3 only after treatment. The drug was administered for 6 to 24 consecutive months with a me...

Adverse reactions to food antigens have been implicated in the pathogenesis of rheumatoid arthritis, even though the mechanism by which food antigens may cause or perpetuate inflammation is still uncertain. In the case of rheumatoid arthritis (RA), dietary manipulation has been shown to alter clinical manifestations [1–3].

Intestinal permeability was measured using cow's milk beta-lactoglobulin absorption (BLG) as a permeability marker in 14 patients with active and inactive rheumatoid arthritis (RA) under three different conditions: after a washout period, after treatment with acetylsalicylic acid (ASA) associated with disodium chromoglycate (DSCG), and with ASA onl...

Intestinal permeability was measured using cow’s milk beta-lactoglobulin absorption (BLG) as a permeability marker in 14 patients with active and inactive rheumatoid arthritis (RA) under three different conditions: after a washout period, after treatment with acetylsalicylic acid (ASA) associated with disodium chromoglycate (DSCG), and with ASA onl...

Using metaphase chromosome spreads as substrate for indirect immunofluorescence technic, we observed anticentromere antibody in three of twenty-five patients affected with various clinical forms of localized scleroderma. Anticentromere antibody is generally considered a serologic marker of the CREST syndrome, a more benign subset of systemic sclero...

Cystic collections in the popliteal space (Baker's cysts) are frequently observed in inflammatory joint diseases. The causal mechanism is generally regarded as entrapment of synovial fluid from the articular space in the gastrocnemio-semimembranosus bursa (Doppman, 1965; Freiberger & Kay, 1979; Wilson et al, 1938); back flow is prevented by a valve...

A 24-year-old woman with systemic lupus erythematosus had, after reduction of corticosteroid therapy, a severe relapse of the disease with hepatitis, nephritis and pleurisy. After admission to the hospital, she was given 60-80 mg/day of prednisone and acute pancreatitis developed on the third day. Plasmapheresis, followed by injection of 1 g of met...

Acute intravenous infusion of fructose was given to 30 normal subjects and 27 normo-uricemic patients affected by psoriasis, 12 with cutaneous involvement only and 15 with psoriatic arthritis. Serum uric acid was measured before and after infusion. A significantly lower increase in serum uric acid levels was found in psoriatic patients in compariso...

In 20 patients affected with rheumatoid arthritis, tissue autoantibodies were studied during a year of treatment with levamisole. Before therapy, antinuclear antibodies were present in 11 cases, anti-thyroid microsomes in 1 and anti-smooth muscle in 6. During therapy, autoantibodies remained almost unchanged in all patients, thus indicating that le...

An intravenous infusion of 2,000 ml isotonic saline was performed in 8 normotensive, normoreninemic patients with progressive systemic sclerosis. None of them had clinical evidence of renal disease. Total and proximal fractional excretion of sodium was reduced when compared with that of 8 normal subjects. No correlation was found with para-aminohip...

In 8 patients affected with rheumatoid arthritis the effects of levamisole administration (150 mg/day once a week) on plasma immunoglobulins were studied. The concentration of IgG, IgA and IgM was measured before and after 15,30,60 and 90 days of treatment. We observed a significant increase of IgG after 30, 60 and 90 days, of IgA after 30 and 90 d...

The fibrin/fibrinogen degradation products were measured in 24 synovial fluids sampled from patients with knee joint effusion. It has been observed that they are increased in synovial fluid involved in inflammatory processes. Their presence and concentration seem to be related to the control of local inflammation.

SUMMARY Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgi- cal synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treat- ments. To determine the safety and efficacy of intra-articular (IA) TNF-α blockade with etanercept (ETN), be...

SUMMARY Objective: We evaluated the induction and clinical significance of ANA, anti-dsDNA and anti-ENA during infliximab therapy in patients with Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS). Methods: We tested sera from 30 RA and 30 AS patients before and during treatment with infliximab. ANA and anti- dsDNA were determined by indirec...

SUMMARY Interleukin 1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1 inhibitor, acting as a "receptor antagonist", which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of...