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The elemental composition of surficial sediments of Venice Lagoon (Italy) in 1987, 1993, 1998 and 2003 were investigated. Zn and Cr concentrations resulted in higher than background levels, but only Cd and Hg were higher than legal quality standards (Italian Decree 2010/260 and Water Framework Directive 2000/60/EC). Contaminants with similar spatial distribution are sorted into three groups by means of correlation analysis: (i) As, Co, Cd, Cu, Fe, Pb, Zn; (ii) Ni, Cr; (iii) Hg. Interannual concentrations are compared by applying a factor analysis to the matrix of differences between subsequent samplings. A general decrease of heavy metal levels is observed from 1987 to 1993, whereas particularly high concentrations of Ni and Cr are recorded in 1998 as a consequence of intense clam fishing, subsequently mitigated by better prevention of illegal harvesting. Due to the major role played by anthropogenic sediment resuspension, bathymetric variations are also considered. [ABSTRACT FROM AUTHOR]

Background: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy., Methods: Between April 9th and April 25th , 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected., Results: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown., Conclusions: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high., Competing Interests: Declaration of competing interest All Authors declare they have no competing interests to report., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Mutations in the TNFRSF1A gene, encoding tumor necrosis factor receptor 1 (TNF-R1), are associated with the autosomal dominant autoinflammatory disorder, called TNF receptor associated periodic syndrome (TRAPS). TRAPS is clinically characterized by recurrent episodes of long-lasting fever and systemic inflammation. A novel mutation (c.262 T > C; S59P) in the TNFRSF1A gene at residue 88 of the mature protein was recently identified in our laboratory in an adult TRAPS patient. The aim of this study was to functionally characterize this novel TNFRSF1A mutation evaluating its effects on the TNF-R1-associated signaling pathways, firstly NF-κB, under particular conditions and comparing the results with suitable control mutations., Methods: HEK-293 cell line was transfected with pCMV6-AC construct expressing wild-type (WT) or c.262 T > C (S59P), c.362G > A (R92Q), c.236C > T (T50M) TNFRSF1A mutants. Peripheral blood mononuclear cells (PBMCs) were instead isolated from two TRAPS patients carrying S59P and R92Q mutations and from five healthy subjects. Both transfected HEK-293 and PBMCs were stimulated with tumor necrosis factor (TNF) or interleukin 1β (IL-1β) to evaluate the expression of TNF-R1, the activation of TNF-R1-associated downstream pathways and the pro-inflammatory cytokines by means of immunofluorescent assay, array-based technique, immunoblotting and immunometric assay, respectively., Results: TNF induced cytoplasmic accumulation of TNF-R1 in all mutant cells. Furthermore, all mutants presented a particular set of active TNF-R1 downstream pathways. S59P constitutively activated IL-1β, MAPK and SRC/JAK/STAT3 pathways and inhibited apoptosis. Also, NF-κB pathway involvement was demonstrated in vitro by the enhancement of p-IκB-α and p65 nuclear subunit of NF-κB expression in all mutants in the presence of TNF or IL-1β stimulation. These in vitro results correlated with patients' data from PBMCs. Concerning the pro-inflammatory cytokines secretion, mainly IL-1β induced a significant and persistent enhancement of IL-6 and IL-8 in PBMCs carrying the S59P mutation., Conclusions: The novel S59P mutation leads to defective cellular trafficking and to constitutive activation of TNF-R1. This mutation also determines constitutive activation of the IL-1R pathway, inhibition of apoptosis and enhanced and persistent NF-κB activation and cytokine secretion in response to IL-1β stimulation.

Objectives: To compare drug survival of different anti-TNF drugs (infliximab, INF, etanercept, ETA, and adalimumab, ADA) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) by analysing data collected from an Italian multicenter observational cohort study., Methods: All patients with RA or SpA registered in the MonitorNet database who started their first course of anti-TNF therapy were included. Overall drug survival was measured, along with specific reasons of discontinuation (inefficacy or adverse events). A first set of analyses using RA as reference category assessed the relationship between diagnosis and drug survival. A second set of analyses stratified by diagnosis (RA and SpA) used INF as reference drug. Adjustment for confounders was performed. The results are presented as adjusted hazard ratios (adjHR) and 95% confidence intervals (95%CI)., Results: 2640 RA patients and 1220 SpA patients with a median follow-up of 17 months (IQR 7.2-33.4) were included in the analyses. Patients with a diagnosis of SpA showed a lower risk of drug discontinuation with an adjHR (95%CI) of 0.81 (0.73, 0.90). In SpA, the subset of patients with ankylosing spondylitis (AS) showed the best survival on treatment. In RA, both ETA and ADA showed a significantly lower probability of withdrawal when compared to INF [adjHR (95%CI) 0.46 (0.38, 0.56) and 0.68 (0.57, 0.81), respectively]. Similar results were found in SpA., Conclusions: Drug survival for SpA is longer than that in RA mainly due to the AS subgroup. In both RA and SpA, ETA and ADA showed a better retention on treatment when compared to INF.

Objectives: Several studies have focused on the antifibrotic potential of the Th1 cytokine IFN-γ-1b through suppression of Th2 fibrogenic functions. It has been reported that IFN-γ induces the production of CXCL11 in the lung and plasma of patients with lung-fibrosis. The aim of the present study was to determine whether the levels of CXCL11 in the bronchoalveolar lavage fluid (BALF) of SSc patients might be a predictor of clinically significant fibrotic lung involvement., Methods: In a retrospective longitudinal study we analysed BALF samples from 16 SSc patients with interstitial lung disease (ILD) and 16 matched control patient without ILD. Patients were eligible if they did not have evidence of ILD at the time of BAL as shown by HRCT. A standard morphological and immunological analysis of BALF cellular components was performed. CXCL11 was measured in BALF by specific ELISA assay., Results: BALF CXCL11 concentrations were significantly elevated in the samples taken from patients who did not developed ILD as compared to those who developed ILD (p<0.001). Stepwise logistic regression analysis revealed that BALF CXCL11 levels predicted clinically significant ILD (p<0.001)., Conclusions: The presence of elevated BALF concentrations of CXCL11 in SSc patients who do not developed lung fibrosis suggest that determination of CXCL11 in BALF could serve as a prognostic factor for pulmonary function decline.

MonitorNet is a database established by the Italian Society of Rheumatology (SIR) in January 2007 and funded by the Italian Medicines Agency (AIFA), for the active long-term follow-up of patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis treated with biologic agents. All hospital Rheumatology Units in Italy were invited to participate in a non-interventional, observational, epidemiological study. The study is conducted in a routine clinical setting (real-world practice) where biologics are prescribed on the basis of current recommendations. In this report we describe the design, methodology, and present preliminary data of the study. At the time of the analysis (April 2009) the database included 3510 patients: 2469 (70.3%) with established RA, 675 (19.2%) with PsA and 366 (10.4%) with AS. The cumulative follow up period was 8,787 patient-years (RA: 8,388, PsA: 157; AS: 242). There were 1,538 adverse events in 938 (26.7%) patients. Infections were recorded in 630 patients, skin-related adverse events in 142 and post-infusion reactions in 90. A total of 30 malignancies were reported. An interim analysis of efficacy was conducted on 2,148 RA patients. Seven hundred and thirty-one patients (35.8%) achieved EULAR remission (defined as DAS28<2.4). When assessed with the more restrictive CDAI and SDAI criteria, the frequency of remission was lower (17.9% and 14.7% respectively). Availability of funding for this study provided an opportunity to organize a collaborative national network of rheumatology clinics to develop a large multicentre observational study.

Objectives: The exact prevalence of erosive osteoarthritis (EOA) is still unknown. Aim of our study was therefore to evaluate the prevalence of osteoarthritis (OA) and EOA of the hand in a representative population from Venetian area., Methods: All people aged > 40 years of a small town in Venetian area has been considered. A complete clinical evaluation has been performed in all subjects. For those patients with clinical signs or symptoms of OA, radiographic evaluation of the hands has been carried out., Results: The entire population aged >40 years living in Silea entered the study. Signs or symptoms of OA were present in 200 out 640 subjects (31.2%), whereas EOA was diagnosed in 17 (8.5%) all female, mean age 57.5 +/-10.1 years (range 41-74) mean disease duration 5.1 +/-3.8 years (range 1-15). The most frequently involved joint was the second DIP of the right hand., Conclusion: The prevalence of EOA in the Venetian area seems to be around 8.5%.

Objective: To assess the prevalence of fibromyalgia in primary Sjögren's syndrome and to evaluate the clinical differences between patients affected with both primary fibromyalgia and primary Sjögren's syndrome and those affected only with primary fibromyalgia., Methods: Clinical features of fibromyalgia were evaluated in 100 consecutive outpatients with primary Sjögren's syndrome and, as controls, in 90 patients with non-insulin-dependent diabetes mellitus, in 75 patients with primary fibromyalgia and in 30 healthy subjects., Results: Fibromyalgia was recorded in 22% of patients with primary Sjögren's syndrome, in 12.2% with diabetes and in 3.3% of healthy controls. In the primary Sjögren's syndrome group the prevalence was significantly higher than in healthy controls (P < 0.01), but not significantly different than in diabetes. Moreover, primary Sjögren's syndrome with fibromyalgia and primary fibromyalgia patients did not differ with respect to the number of tender points, while the mean pain threshold was lower in the latter (P = 0.05). Purpura, hypergammaglobulinemia, rheumatoid factor, and a focus score > or = 1 on lip biopsy were significantly more frequent in primary Sjögren's syndrome patients without than with fibromyalgia., Conclusions: As recently reported by other authors, our study confirms the moderate increase of fibromyalgia prevalence in primary Sjögren's syndrome. Typical fibromyalgic findings are quite similar to those of primary fibromyalgia, but surprisingly, primary Sjögren's syndrome patients with fibromyalgia show a less severe global involvement than those with primary Sjögren's syndrome alone.