GISEA: an Italian biological agents registry in rheumatology

The GISEA registry is an independent database that was established by the Italian Group for the Study of Early Arthritis (GISEA) in 2008, funded by the Italian Association of Rheumatic Patients (ANMAR - ONLUS). In line with the network's epidemiological strategy, the initial protocol was designed to collect long-term follow-up data concerning patients with rheumatic diseases treated with biological agents in order to investigate the realworld characteristics in terms of disease activity, comorbidities and survival on treatment. We here describe the design and methodology used to collect patient data. Information concerning demographics, disease activity, treatment changes (including the reasons for changing and the duration of each therapy), concomitant therapies and adverse events is available to all the members of the study groups by means of a web-based interface that allows queries and the presentation of numerical data, as well as graphics to illustrate trends. Fourteen Italian rheumatology centres have contributed patients to the database which, at the time writing, includes 5145 patients (72% women) with a mean age of 53 years (range 16-88). The initial diagnoses were rheumatoid arthritis (3494 patients, 67.9%), psoriatic arthritis (833, 16.2%), ankylosing spondylitis (493, 9.6%), undifferentiated spondylo-arthritides (307, 5.9%), enteropathic arthritis (14, 0.3%) and spondylitis following reactive arthritis (4, 0.1%). These patients have been followed for up to 10 years, and 1927 (35.8%) have been treated for at least three years. The biological treatments received include etanercept, infliximab, anakinra, adalimumab, abatacept, rituximab and tocilizumab. A total of 2926 adverse events have been observed, with 1171 patients (22%) reporting at least one. Analysis of the accumulated data will provide insights into the critical early phase of the studied arthritides, and enable us to identify the clinical and laboratory profiles that may predict responsiveness to a specific therapy

Thymosin β4 and β10 in Sjögren's syndrome: Saliva proteomics and minor salivary glands expression

Background: In the present study, we investigated whether thymosin β (Tβ) in saliva and in minor salivary glands is differentially expressed in patients with primary Sjögren's syndrome (pSS) and patients with autoimmune diseases (systemic sclerosis [SSc], systemic lupus erythematosus [SLE], and rheumatoid arthritis [RA], with and without sicca syndrome [ss]). Methods: Saliva specimens of nine patients with pSS, seven with ss/SSc, seven with ss/SLE, seven with ss/RA, seven with SSc, seven with SLE, and seven with RA, as well as ten healthy subjects, were analyzed using a high-performance liquid chromatograph coupled with a mass spectrometer equipped with an electrospray ionization source to investigate the presence and levels of Tβ4, Tβ4 sulfoxide, and Tβ10. Immunostaining for Tβ4 and Tβ10 was performed on minor salivary glands of patients with pSS and ss. Results: Tβ4 levels were statistically higher in patients with pSS with respect to the other subgroups. Tβ10 was detectable in 66.7 % of patients with pSS and in 42.8 % of those with ss/SSc, while Tβ4 sulfoxide was detectable in 44.4 % of patients with pSS and in 42.9 % of those with ss/SSc. Tβ10 and Tβ4 sulfoxide were not detectable in patients without associated ss and in healthy control subjects. Regarding thymosin immunostaining, all patients had immunoreactivity for Tβ10, and a comparable distribution pattern in the four different subgroups of patients was observed. Tβ4 immunoreactivity was present in patients with ss/SSc and those with ss/SLE, while it was completely absent in patients with pSS and those with ss/RA. Conclusions: Our data show that higher salivary Tβ expression characterizes patients with pSS, while Tβ4 sulfoxide and Tβ10 salivary expression was selectively present in patients with sicca symptoms. Moreover, at the immunohistochemical level in patients with pSS, minor salivary glands showed a peculiar pattern characterized by immunostaining for Tβ10 in acinar cells in the absence of any reactivity for Tβ4. These findings, taken together, suggest a different role for Tβ4 and Tβ10 in patients with pSS who have ss and other autoimmune disease

The Italian registry of aggressive rheumatoid arthritis -- the GIARA project.

Objective. In 1999, the Italian Society of Rheumatology started a project to determine the prevalence and clinical characteristics of aggressive rheumatoid arthritis (ARA). Methods. For I year, all patients with RA for 2 to 2 to 1.5, female sex, and RF positivity. Conditions other than RA were recorded in about 50% of the patients, and only 30%-40% were taking disease modifying antirheumatic drugs. Conclusion. In an Italian RA population, the GIARA (Gruppo Italiano Artrite Reumatoide Aggressiva) criteria for ARA were met by 15% of the patients with disease duration of 2 years, but erosions were seen in 35%. Upon referral, most of the RA patients were inadequately treated and had other conditions

Intraplate strike-slip faulting in East Antarctica: new geophysical views from the Rennick Graben and Wilkes Subglacial Basin

Intraplate strike-slip faulting can occur in association with different geodynamic settings, ranging from subduction-related to collision and extension. Geological and geophysical research in Northern Victoria Land (NVL) in East Antarctica, has led to the interpretation that major fault systems that were active during the early Paleozoic Ross Orogen were reactivated much later as right-lateral intraplate strike-slip fault systems from ca 48 Ma, and that these faults may have accomodated differential shear along evolving oceanic transform faults located between southeastern Australia and Tasmania. One of the main structures in NVL that has been inferred to relate to this unusual geodynamic process is the Rennick Graben (RG), but its age, extent and kinematics have remained both poorly constrained and controversial. Even less well-understood are the potential tectonic linkages between the RG and the deep sub-basins that lie within the much broader Wilkes Subglacial Basin (WSB), in the hinterland of the Transantarctic Mountains. Here, we present new interpretations of enhanced potential field images derived from aeromagnetic and airborne and land-gravity observations to help constrain the extent and architecture of the RG and the sub-basins within the WSB. We show that the RG is a composite pull-part basin that extends from the Oates Coast towards the margin of the Ross Sea Rift, part of the West Antarctic Rift System. We suggest that the more cratonic WSB region was also affected by extensional and transtensional processes, the latter potentially linked to an evolving and distributed left-lateral Paleogene(?) strike-slip plate boundary between East Antarctica and Australia

The role of lithospheric flexure in the landscape evolution of the Wilkes Subglacial Basin and Transantarctic Mountains, East Antarctica

Reconstructions of the bedrock topography of Antarctica since the Eocene–Oligocene Boundary (ca. 34 Ma) provide important constraints for modelling Antarctic ice sheet evolution. This is particularly important in regions where the bedrock lies below sea level, since in these sectors the overlying ice sheet is thought to be most susceptible to past and future change. Here we use 3D flexural modelling to reconstruct the evolution of the topography of the Wilkes Subglacial Basin (WSB) and Transantarctic Mountains (TAM) in East Antarctica. We estimate the spatial distribution of glacial erosion beneath the East Antarctic Ice Sheet, and restore this material to the topography, which is also adjusted for associated flexural isostatic responses. We independently constrain our post‐34 Ma erosion estimates using offshore sediment stratigraphy interpretations. Our reconstructions provide a better‐defined topographic boundary condition for modelling early East Antarctic Ice Sheet history. We show that the majority of glacial erosion and landscape evolution occurred prior to 14 Ma, which we interpret to reflect more dynamic and erosive early ice sheet behaviour. In addition, we use closely‐spaced 2D flexural models to test previously proposed hypotheses for a flexural origin of the TAM and WSB. The pre‐34 Ma topography shows lateral variations along the length of the TAM and WSB that cannot be explained by uniform flexure along the front of the TAM. We show that some of these variations may be explained by additional flexural uplift along the south‐western flank of the WSB and the Rennick Graben in northern Victoria Land

Electrical structure across a major ice-covered fault belt in northern Victoria Land (East Antarctica)

A Geomagnetic Depth Sounding profile was performed across the glaciated Rennick Graben and the adjacent fault-bounded terranes of northern Victoria Land in East Antarctica. Induction arrows analysis and a 2D inversion model provide a unique deep electrical resistivity window beneath these fault zones. The electrical resistivity break across the Lanterman Fault is apparently restricted to the upper crust, suggesting that this strike-slip fault may not represent a deep lithospheric suture. Further east, a westward-dipping conductor is traced to a depth of 40 km beneath the Robertson Bay Terrane. It may image a remnant of the paleo-Pacific oceanic plate, which subducted beneath the Bowers Terrane. Within the Wilson Terrane, the Rennick Graben is an upper-crust resistive block. The Rennick Graben lacks a deep crustal or upper mantle conductor, in contrast to several continental rifts. However, similar resistive lower crust underlies some other major strike-slip fault belts

Allele *2 of the HS1,2A enhancer of the Ig regulatory region associates with rheumatoid arthritis

Objective: To investigate the role of the HS1.2 enhancer polymorphisms as a new candidate marker for rheumatoid arthritis (RA) and to define the possible association with autoantibody positivity and clinical outcome. Methods: Genomic DNA was obtained from two cohorts of patients with RA (100 with early RA (ERA) and 114 with longstanding RA (LSRA)) and from 248 gender-matched controls from the same geographical area. Clinical and immunological characteristics were recorded for all the patients. Results: The percentage of the 2/2 genotype was higher In patients with ERA (27.0%), and In patients with LSRA (34.2%), than In controls (14.9%) (ERA: OR = 2.11 (95% Cl 1.20 to 3.70) vs controls; LSRA: OR = 2.96 (95% Cl 1.76 to 5.00) vs controls). A lower representation of allele *3 was present In patients with ERA (2.0%) than In controls (6.0%; OR = 0.32 (95% Cl 0.11 to 0.91)). No significant associations were found between polymorphisms and autoantibodies positivity. Conclusion: The HS1.2A allele *2 associates with early and longstanding RA

Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry

Objectives: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry.Patients and methods: This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model.Results: Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis.Conclusion: Although ETA demonstrated a high persistence in biologic-naive RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug

4D Antarctica: a new effort aims to help bridge the gap between Antarctic crust and lithosphere structure and geothermal heat flux

Seismology, satellite-magnetic and aeromagnetic data, and sparse MT provide the only available geophysical proxies for large parts of Antarctica\u2019s Geothermal Heat Flux (GHF) due to the sparseness of direct measurements. However, these geophysical methods have yielded significantly different GHF estimates. This restricts our knowledge of Antarctica\u2019s contrasting tectono-thermal provinces and their influence on subglacial hydrology and ice sheet dynamics. For example, some models derived from aeromagnetic data predict remarkably high GHF in the interior of the West Antarctic Rift System (WARS), while other satellite magnetic and seismological models favour instead a significantly colder rift interior but higher GHF stretching from the Marie Byrd Land dome towards the Antarctic Peninsula, and beneath parts of the Transantarctic Mountains. Reconciling these differences in West Antarctica is imperative to better comprehend the degree to which the WARS influences the West Antarctic Ice Sheet, including thermal influences on GIA. Equally important, is quantifying geothermal heat flux variability in the generally colder but composite East Antarctic craton, especially beneath its giant marine-based basins. Here we present a new ESA project- 4D Antarctica that aims to better connect international Antarctic crust and lithosphere studies with GHF, and assess its influence on subglacial hydrology by analysing and modelling recent satellite and airborne geophysical datasets. The state of the art, hypotheses to test, and methodological approaches for five key study areas, including the Amundsen Sea Embayment, the Wilkes Subglacial Basin and the Totten catchment, the Recovery and Pensacola-Pole Basins and the Gamburtsev Sublgacial Mountains/East Antarctic Rift System are highlighted

Italian consensus on the recommendations about the use of methotrexate for the treatment of rheumatic diseases with a focus on rheumatoid arthritis: results from the "3E initiative"

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