This chapter describes how the design tool WebRatio (and its companion conceptual model WebML) have been extended to support the new requirements imposed by rich Internet applications (RIAs), that are recognized to be one of the main innovations that lead to the Web 2.0 revolution. Complex interactions such as drag and drop, dynamic resizing of visual components, graphical editing of objects, and partial page refresh are addressed by the RIA extensions of WebRatio. The chapter discusses what kinds of modelling primitives are required for specifying such patterns and how these primitives can be integrated in a CASE tool. Finally, a real industrial case is presented in which the novel RIA features are successfully applied.

Musculoskeletal conditions represent one-third to more than one-half of all non-communicable disease multimorbidities in the elderly, worsening their disability because of pain and limited physical function, often concurring with their mental decline. Musculoskeletal conditions significantly contribute to frailty and global disability, second only to mental health conditions. Furthermore, premature mortality, generally due to an increased risk of developing cardiovascular disease, has been documented in several rheumatic diseases, including osteoarthritis, gout, vasculitis, etc., which largely affect older people. In the elderly, rheumatic diseases cover a spectrum of conditions affecting all age groups, especially those are seen more often in the aging population. This non-systematic review focuses on the elderly and may hopefully contribute to raising awareness of these issues beyond the rheumatology community. We believe that this constitutes a critical step for prompt and proper diagnosis and referral of patients to ameliorate their overall long-term outcome.

ObjectiveAntimalarials have been associated with QT prolongation in COVID-19 patients but are generally safe in systemic lupus erythematosus (SLE).We compared the prevalence of QTc prolongation between COVID-19 and SLE patients treated with hydroxychloroquine (HCQ). Methods We included patients with SARS-CoV-2 infection confirmed by nasopharyngeal swab and patients taking HCQ for SLE.A prolonged QTc was defined as an increase in QTc intervals >60 ms (compared with baseline) or as a QTc of ≥500 ms. We performed the univariate and multivariate logistic regression to investigate the risk factors for QTc prolongation in COVID-19 patients. Results We enrolled 58 COVID-19 patients (median age 70.5 years, IQR 25), grouped into group A (patients with HCQ) group B (patients with HCQ + azithromycin) and group C (not received either drug). Fifty (26%) COVID-19 patients presenteda QTc prolongation (12 QTc≥500 ms, 3 patients ΔQTc>60 ms). We did not find any differences in QTc prolongation among the three treatment groups. Baseline QTc were independently associated to QTc prolongation. Compared to the 50 SLE patients (median age 38.5 years, IQR 22), chronically treated with HCQ, COVID-19 patients showed significantly longer QTc (p<0.001). ConclusionThis is the first study demonstrating that, unlike COVID-19 patients, patients with SLE are not susceptible to HCQ-induced long QT syndrome and arrhythmia. The combined arrhythmogenic effect of SARS-CoV-2 infection and HCQ could account for the excess of QTc prolongation and fatal arrhythmias described in patients with

BackgroundIn psoriatic arthritis (PsA) and rheumatoid arthritis (RA) systemic inflammation is known to cause endothelial dysfunction(1). Nailfold videocapillaroscopy (NVC) analyzes in vivo blood vessels, looking for alterations due to microvascular damage, and its application in these pathologies often highlights interesting abnormalities. PsA is characterized by lower mean capillary length and density and abnormal morphology, such as tight terminal convolutions. In RA typically elongated and dilated capillaries and prominent subpapillary plexus are described(2, 3). Differences between RA and PsA NCV patterns are known but not well defined yet(3).ObjectivesAim of our study was to evaluate the microvascular features circulation by NVC in patients affected by PsA and RA, looking for possible differences that may characterize the two diseases.MethodsWe recruited outpatients affected by PsA or RA classified according to standard criteria(4, 5) referring to the Rheumatology Unit at Sapienza University of Rome. Healthy controls (HCs) without known risk factors for nailfold capillary alterations(6) were also recruited. Patients and HCs underwent NVC with a 200x magnification lens. The following morphological parameters were considered: number of capillaries per square millimeter, alterations in length, dimension, morphology and distribution of the capillary; presence of ectatic loops, hemorrhages, flux abnormalities(7, 8). A semi-quantitative rating scale was adopted to score these changes, according to previous studies(9). The mean score for each subject was obtained by analyzing all fingers, except the thumbs.For the statistical analysis, Chi-square and Mann-Whitney tests were used. All tests were two-sided with a significance level set at p<0.05.ResultsWe recruited 34 patients (20 with PsA and 14 with RA) and 30 HCs. For patients, the mean age was 61,7 years (SD 15,4), median disease duration was 184 months (SD 204) and males were 18 (53%). Active or past smokers were 11 (18%), 9 (15%) suffered from arterial hypertension and 2 (0.03%) from type 2 diabetes mellitus. Raynaud’s phenomenon was present in 4 patients with PsA (20%) and 6 with RA (43%).The most frequent morphological changes were tortuous capillaries (90% in PsA and 100% in RA), single-crossing shape (90% and 86%) and bizarre capillaries (30% in both groups) while multiple crossing and ramified capillaries were present in 50% and 21 % RA patients only.With respect to HCs, we found significantly more frequent changes concerning morphology, ectatic loops, presence of hemorrhages and capillary plexus visibility in both PsA and RA patients. Moreover, patients with RA showed significantly more frequent abnormalities of the blood flow with respect to HCs. These results are shown in Table 1.Table 1.Comparison of the main NVC changes in patients and HCs.NVC ChangesHCPsARAN (%)N (%)P value vs HCsN (%)P value vs HCsMorphology3 (10%)14 (70%)p<0.000112 (86%)p<0.0001Ectatic loops0 (0%)11 (55%)p<0.00018 (57%)p<0.0001Hemorrhages2 (0.07%)1 (5%)p<0.016 (43%)p<0.0058Plexus19 (63%)10 (50%)p<0.027 (50%)p<0.02Flux abnormalities3 (10%)6 (30%)p>0.055 (36%)p<0.026The presence of hemorrhages was significantly higher in RA rather than in PsA patients (p<0.01). No significant differences were found in number, length, and distribution of capillaries between PsA/RA cases and HCs.ConclusionOur study confirms and completes the frame of NCV alterations in PsA and RA. We described for the first time alterations in the capillary morphology and the presence of hemorrhages in both groups of patients with respect to HCs. It remains to evaluate how these findings can reflect the microvascular environment of chronic arthritis.References[1]Fromm, S et al. Arthritis Res Ther 2019[2]Lambova SN, Müller-Ladner U. Microvasc Res 2012[3]Graceffa D, et al. Arthritis 2013[4]Taylor W, et al. Arthritis Rheum 2006[5]Aletaha D, et al. Ann Rheum Dis 2010[6]Ciaffi J, et al. Microvasc Res 2020[7]Maricq HR. Arthritis Rheum 1981[8]Smith V, et al. Autoimmun Rev. 2020[9]Cutolo M, et al. J Rheumatol 2000Disclosure of InterestsNone declared

Background Screening for latent tuberculosis infection is recommended in patients with rheumatoid arthritis (RA) starting Janus kinase inhibitors (Jaki). Interferon (IFN)-gamma release assays (IGRAs) are increasingly used for this purpose. Jaki tend to decrease the levels of IFNs, questioning the reliability of IGRAs during treatment with these drugs. Objectives To compare the performance of QuantiFERON-TB Gold Plus (QFT-P) and QFT Gold In-tube (QFT-GIT) in RA patients treated with Jaki. Methods RA patients underwent QFT-P and QFT-GIT at baseline (T0), and after 3 (T3) and 12 months (T12) of treatment with Jaki. The agreement between the two tests was calculated. The agreement between IGRAs and tuberculin skin test (TST) or chest radiography at baseline was also determined. The variability of QTF-P results was longitudinally assessed. Results Twenty-nine RA patients (F/M 23/6; median age/IQR 63/15.5 years; median disease duration/IQR 174/216 months) were enrolled. A perfect agreement was found between QFT-P and QFT-GIT at all times (κ = 1). At T0, no agreement was recorded between IGRAs and TST (κ = -0.08) and between TST and chest radiography (κ = -0.07), a low agreement was found between QFT-P and chest radiography (κ = 0.17). A variation of 33.3% in the results of QFT-P was recorded at T3 vs T0, of 29.4% at T12 vs T0, and of 11.8% at T12 vs T3. The median levels of IFN-γ produced by lymphocytes in response to the mitogen of QFT-P decreased after 3 months followed by an increase after 12 months (not significant). No change in the median number of circulating lymphocytes was documented. Glucocorticoids intake was associated with a higher probability of negative or indeterminate IGRA results at T0 (p<0.0001). Conclusion A response to IGRAs is detectable during treatment with Jaki. However, fluctuations in the results of IGRAs have been observed in the absence of correlation with clinical outcomes, thus challenging their interpretation.