Dr. Favalli, et al. reply

We thank Dr. So, et al1 for the interest in our letter2 and for sharing the results about the coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE) in Hong Kong1 We agree that the quantification of the risk of infection with severe acute respiratory coronaviruses-2 (SARS-CoV-2) in patients with SLE is a major concern

Reply to the Comment on “Lost tsunami by M.T.Pareschi et al.”, by Luigi Vigliotti

No abstrac

Topographic control on lava flow paths at Mt. Etna (Italy): implications for hazard assesment

Assessment of the hazard from lava flow inundation at the active volcano of Mt. Etna (Italy) was performed by calculating the probability of lava flow inundation at each position on the volcano. A probability distribution for the formation of new vents was calculated using geological and volcanological data from past eruptions. The simulated lava flows from these vents were emplaced using a maximum expected flow length derived from geological data on previous lava flows. Simulations were run using DOWNFLOW, a DEM-based model designed to predict lava flow paths. Different eruptive scenarios were simulated by varying the elevation and probability distribution of eruptive points. Inundation maps show that the city of Catania and the coastal zone may only be impacted by flows erupted from low-altitude vents (< 1500 m elevation), and that flank eruptions at elevations > 2000 m preferentially inundate the northeast and southern sectors of the volcano as well as the Valle del Bove. Eruptions occurring in the summit area (> 3000 m elevation) pose no threat to the local population. Discrepancies between the results of simple, hydrological models and those of the DOWNFLOW model show that hydrological approaches are inappropriate when dealing with Etnean lava flows. Because hydrological approaches are not designed to reproduce the full complexity of lava flow spreading, they underestimate the catchment basins when the fluid has a complex rheology

POS0048 SEROPREVALENCE OF ANTI-SARS-COV-2 ANTIBODIES IN RHEUMATIC PATIENTS TREATED WITH BIOLOGICAL AND TARGETED THERAPY LIVING IN LOMBARDY, ITALY (MAINSTREAM PROJECT)

Background:Emerging observational data have shown that rheumatic patients seem not to be more susceptible to SARS-CoV-2 infection neither to worse outcomes. However, the true prevalence of COVID19 is still unknown due to the high proportion of subclinical infection. In this scenario, measuring the seroprevalence of SARS-CoV-2 may be crucial to improve the knowledge about the impact of COVID19 in rheumatic patients.Objectives:To estimate in a COVID19 high-endemic area (Lombardy, Italy) the prevalence of anti-SARS-CoV-2 antibodies in a large cohort of patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) treated with biologic (b-) or targeted synthetic (ts-) disease modifying drugs (DMARDs).Methods:A seroprevalence cross-sectional study was conducted in the period between 4th May and 16th June 2020, including patients with confirmed RA or SpA treated with b- or tsDMARDs. Patients were tested for anti-SARS-CoV-2 IgG, IgM and IgA antibodies against main viral antigens (nucleoprotein [N], spike 1 [S1], receptor-binding domain [RBD]) using ELISA. These data were compared with those observed in the healthy population in the same period and region. Patients also answered a questionnaire on history of symptoms consistent with COVID19, risk factors and comorbidities. Serological response to RBD was evaluated according to symptom severity (asymptomatic, minor, or major [respiratory and fever >37.5°C] symptoms).Results:The study population included 300 patients (62% females, mean age 53 years, 20% over 65 years old) diagnosed with RA (56%), psoriatic arthritis (23%), or ankylosing spondylitis (21%), treated with anti-TNF (57%), abatacept (20%), anti-IL6 (11%), or JAK inhibitors (5%). Four patients (1.3%) referred a prior diagnosis of COVID19 defined by nasopharyngeal swab. Immunoglobulin titers were evaluated resulting in 9%, 13.6%, and 13.3% positive patients for IgG, IgM and IgA, respectively (Table 1), with no significant difference to the healthy population. Among seropositive patients, 55.3% were asymptomatic, 16% had minor and 19.6% major symptoms, 7.1% were hospitalized. No deaths or admission to intensive care units occurred. IgM, IgG and IgA titers to RBD were higher in patients with both minor and major symptoms compared with asymptomatic ones (Figure 1). No differences were found between seronegative and seropositive patients in relation to age, sex, rheumatic diagnosis, and treatments with b- or tsDMARDs. A relative lower risk of seropositivity was observed in patients receiving concomitant methotrexate (RR 0.49, 95% CI 0.25-0.94; p 0.04), while an increased risk was associated with obesity (RR 2.33, 95% CI 1.26-3.79; p 0.019) and presence of at least 2 comorbidities (RR 1.94, 95% CI 1.11-3.15; p 0.037). Corticosteroids use was numerically more frequent in seropositive than seronegative patients (18% vs 14%).Conclusion:This study confirms that, even in a cohort of rheumatic patients, the spread of SARS-CoV-2 infection is much greater than that observed by capturing only swab-diagnosed COVID19 cases. The underlying rheumatic disease and ongoing therapy with b/ts-DMARDs do not seem to impact SARS-CoV-2 antibody positivity, which conversely seems to be proportional to the intensity of COVID19 symptoms and less frequent in patients receiving concomitant methotrexate. The project was co-financed by Lombardy Region 2014-2020 Regional Operational Programme under the European Regional Development Fund.Table 1.Prevalence of specific anti-SARS-CoV-2 antibodies.AntibodiesPosivite(n)Seroprevalence (%)(95% CI)IgG279%(6.2 – 12.7)IgG anti-N268.6%(5.9 – 12.3)IgG anti-RBD206.6%(4.3 – 10)IgG anti-S1186%(3.8 – 9.2)IgM4113.6%(10.2 – 18)IgM anti-N3511.6%(8.5 – 15.7)IgM anti-RBD258.3%(5.7 – 12)IgA4013.3%(9.9 – 17.6)IgA anti-N3712.3%(9.0 – 16.5)IgA anti-RBD258.3%(5.7 – 12)IgG+IgM237.6%(5.1 – 11.2)IgG+IgM+IgA227.3%(4.9 – 10.5)IgG+IgA248%(5.4 – 11.6)IgG/IgM/IgA5618.6%(14.6 – 23.4)Figure 1.Antibody levels (S/Co) against SARS-CoV-2 RBD.Disclosure of Interests:None declared

POS1182 MANAGEMENT OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS DURING THE COVID-19 PANDEMIC: EVIDENCE FROM THE ITALIAN EPICENTER

Background:Despite significant improvement in the RA management, up to twenty percent of patients with rheumatoid arthritis (RA) have a difficult-to-treat (D2T) disease. The COVID-19 related mitigation policies, for instance quarantine, and consequent difficult access to in-person visits, laboratory and imaging investigations, adversely affected the follow up of rheumatic patients. Although pandemic-imposed limitations could have negatively influenced disease management particularly in D2T patients, to what degree these restrictions affected the treat-to target (T2T) and tight-control strategy in this subgroup of RA patients has not been investigated yet.Objectives:To evaluate whether the switch to telehealth imposed by COVID-19 pandemic was effective in the management of D2T RA patients treated with targeted therapies.Methods:This observational retrospective real-life study was conducted from November 2019 through September 2020. Among RA patients treated with targeted therapies, RA D2T patients according to EULAR definition (1) were identified. Clinical Disease Activity Index (CDAI) of these patients was analysed retrospectively before, during and after lockdown (LD). During LD period, patients could choose whether to receive home drug delivery or to maintain their face-to-face consultations, and in the former rheumatologists provided virtual care. To evaluate the effect of LD on the percentage of patients in remission, logistic mixed effects regression models were fitted, with CDAI remission as response variable.Results:Data were extracted from a longitudinal observational registry, and at baseline, 52 patients treated with targeted therapies were classified as D2T RA. Among them, during pre-LD, LD, and post-LD 11.54% (N=6), 53.49% (N=23), and 46.15% (N=24) had CDAI remission/low disease activity, while 46 (88.46%), 20 (46.51%) and 28 (53.85%) had CDAI moderate/high. All the patients completed the follow-up. Median values of CDAI during pre-LD, LD, and post-LD were 14.5 [IQR 12-21], 9 [IQR 5.5-16], and 11 [IQR 6-19.2] respectively (see Figure 1 below).Conclusion:Telephone-based tight control strategy ensured satisfactory management of D2T RA treated with targeted therapies. This temporary approach has been a feasible compensation for the decline of face-to-face visits also in this challenging group of RA patients, thus reassuring for future months before the end of pandemic.References:[1]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80(1):31-35.Disclosure of Interests:Francesca Ingegnoli: None declared, Angela Flavia Luppino: None declared, Gilberto Cincinelli: None declared, Ennio Favalli Speakers bureau: AbbVie, Sanofi-Genzyme, Lilly, UCB, Pfizer, Novartis, Janssen, Paid instructor for: Roche, MSD, Consultant of: Lilly, Galapagos, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly,Janssen, MSD

POS0575 THE PATIENT GLOBAL ASSESSMENT (PGA) OF DISEASE ACTIVITY COLLECTS DIFFERENT INFORMATION IN EARLY COMPARED TO ESTABLISHED RHEUMATOID ARTHRITIS

Background:The patient global assessment (PGA) is the most widely used patient-reported measure in rheumatoid arthritis (RA), being a component of disease activity scores and definitions of remission. Studies have however shown that, at least in established RA, PGA is mostly associated with pain, functional limitation, psychological distress and comorbidities, rather than with objective measures of inflammation. As such, the inclusion of PGA as a driver of intensification of immunosuppressive therapy is been questioned. Determinants of PGA may however differ in the earliest stages of RA, when pain processing mechanisms and damage accrual have not occurred yet. Whether the association of PGA with disease activity in RA changes over time is at present undetermined.Objectives:To analyze the associations between PGA and disease activity measures in patients with RA across different phases of the disease.Methods:1.002 RA patients from two independent cohorts were included: 1) a prospective longitudinal cohort of early RA (5 years) (n=401) with inadequate response to methotrexate. Determinants of PGA were assessed by Pearson's correlation coefficients and multivariable linear regression.Results:In early RA, median (IQR) symptom duration at inclusion was 15 (9-27) weeks, 71.5% of the patients were female, 49.3% were autoantibody-positive, and 30% had radiographic evidence of ≥1 erosion. The mean (SD) DAS28 was 4.94 (1.19), and the mean (SD) PGA 57.6 (26.6). The proportion of patients at least in low disease activity (DAS28 0.40) at all time points, and were independent of other co-variates (Table 1). Swollen joints (SJC28) were independently and directly associated with PGA at all time points until 12 months, whilst the association become indirect at 24 months (Table 1). In ACPA-positive patients, PGA at 6 and 12 months was weakly but still significantly associated with SJC28 even in low disease activity states (adj r 0.15 and 0.13, p<0.05). Patients with established RA had a mean [SD] DAS28 of 5.3 [1.2] and were ACPA-positive in 69.6% of the cases. Independent determinants of PGA were pain, HAQ and tender joints, whilst no associations with SJC28 and acute phase reactants were found neither in the overall cohort nor in ACPA-positive patients.Conclusion:In established RA, PGA appears mostly related to factors outside the core domains of disease activity. In contrast, in the early phases of the disease, PGA may more strictly collect information on inflammatory-related symptoms. Better understanding of the relationship between patient reported outcomes and disease activity in the various phases of RA may thus be needed before introducing definitive changes in the current definitions of disease activity.References:[1]Nikiphorou E et al. Arthritis Res Ther 2016;18:251[2]Ferreira RJO et al. Ann Rheum Dis 2019;78:e109.Table 1.Associations of PGA in early RA at different time points0 months6 months12 months24 monthsr (95% CI)pr (95% CI)pr (95% CI)pr (95% CI)pVAS pain0.74 (0.70-0.77)<0.0010.83 (0.80-0.86)<0.0010.84 (0.80-0.86)<0.0010.83 (0.79-0.87)<0.001HAQ0.47 (0.41-0.54)<0.0010.54 (0.46-0.62)<0.0010.57 (0.50-0.63)<0.0010.50 (0.41-0.59)<0.001SJC280.27 (0.19-0.35)<0.0010.27 (0.18-0.35)<0.0010.21 (0.12-0.30)<0.0010.23 (0.13-0.33)<0.001TJC280.34 (0.27-0.41)<0.0010.39 (0.31-0.47)<0.0010.39 (0.30-0.46)<0.0010.30 (0.20-0.40)<0.001CRP0.08 (0.00-0.17)0.050.09 (0.00-0.19)0.070.19 (0.10-0.28)<0.0010.03 (0.09-0.14)0.63β standpβ standpβ standpβ standpVAS pain0.66<0.0010.76<0.0010.74<0.0010.80<0.001HAQ0.20<0.0010.180.010.200.030.220.003SJC280.170.030.150.040.110.04----TJC28----------------CRP------------Acknowledgements:I have no acknowledgements to declare.Disclosure of Interests:Ludovico De Stefano: None declared, Serena Bugatti Speakers bureau: BMS, Lilly, Sanofi, Pfizer, Galapagos, Bernardo D'Onofrio: None declared, Ennio Favalli Speakers bureau: AbbVie, MSD, Novartis, Pfizer, UCB Pharma, Antonio Manzo: None declared, Roberto Caporali Speakers bureau: AbbVie, BMS, Celgene, HSD, Lilly, Pfizer, Roche, UCB Pharma, Carlomaurizio Montecucco Speakers bureau: BMS, Lilly, Sanofi, Pfizer, Galapagos, Roche, Novarti

TINITALY/01: a new Triangular Irregular Network of Italy

A new Digital Elevation Model (DEM) of the natural landforms of Italy is presented. A methodology is discussed to build a DEM over wide areas where elevation data from non-homogeneous (in density and accuracy) input sources are available. The input elevation data include contour lines and spot heights derived from the Italian Regional topographic maps, satellite-based global positioning system points, ground based and radar altimetry data. Owing to the great heterogeneity of the input data density, the DEM format that better preserves the original accuracy is a Triangular Irregular Network (TIN). A Delaunay-based TIN structure is improved by using the DEST algorithm that enhances input data by evaluating inferred break-lines. Accordingly to this approach, biased distributions in slopes and elevations are absent. To prevent discontinuities at the boundary between regions characterized by data with different resolution a cubic Hermite blending weight S-shaped function is adopted. The TIN of Italy consists of 1.39×109 triangles. The average triangle area ranges from 12 to about 13000 m2 accordingly to different morphologies and different sources. About 50% of the model has a local average triangle area <500 m2. The vertical accuracy of the obtained DEM is evaluated by more than 200000 sparse control points. The overall Root Mean Square Error (RMSE) is less than 3.5 m. The obtained national-scale DEM constitutes an useful support to carry out accurate geomorphological and geological investigations over large areas. The problem of choosing the best step size in deriving a grid from a TIN is then discussed and a method to quantify the loss of vertical information is presented as a function of the grid step. Some examples of DEM application are outlined. Under request, an high resolution stereo image database of the whole Italian territory (derived from the presented DEM) is available to browse via internet

The combined use of VIGl@ct (R) (bioMerieux) and fluorescent amplified length fragment polymorphisms in the investigation of potential outbreaks

Even with good surveillance programmes, hospital-acquired infections (HAls) are not always recognized and this may lead to an outbreak. In order to reduce this risk, we propose a model for prompt detection of HAls, based on the use of a real-time epidemiological information system called VIGI@ct (R) (bioMerieux, Las Balmas, France) and on the rapid confirmation or exclusion of the genetic relationship among pathogens using fluorescent amplified length fragment polymorphism (f-AFLP) microbial fingerprinting. We present the results of one year's experience with the system, which identified a total, of 306 suspicious HAls. Of these, 281 (92%) were 'confirmed' by clinical evidence, 16 (5%) were considered to be simple colonization and the tatter nine (3%) were archived as 'not answered' because of the absence of the physician's cooperation. There were seven suspected outbreaks; of these, f-AFLP analysis confirmed the clonal relationship among the isolates in four cases: outbreak 1 (four isolates of Pseudomonas aeruginosa), outbreak 2 (three Escherichia coli isolates), outbreak 6 (two Candida parapsilosis isolates) and outbreak 7 (30 ESPL-producing Klebsiella pneumoniae subsp. pneumoniae). Based on our results, we conclude that the combination of VIGI@ct (R) and f-AFLP is useful in the rapid assessment of an outbreak due to Gram-positive or Gramnegative bacteria and yeasts. (C) 2007 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved

hla typing in systemic sclerosis

Objective: the aim of the study was to investigate the relationship between Systemic Sclerosis (SSc) and HLA antigens, and to correlate these antigens with the clinical manifestations of the disease. Materials and methods: 55 patients were stratified according a) to the cutaneous involvement b) to the positivity of Scl- 70 and anticentromere antibody and c) to the internal organ involvement, in particular we used HRCT to demonstrate lung fibrosis, echocardiography for the diagnosis of pulmonary hypertension, blood creatinine, urinalysis and arterial hypertension to demonstrate renal failure, and esophagus double-countrast barium swallow for the diagnosis of esophagopathy. The control group consisting of 2000 healthy Caucasian subjects was recruited from the same population. Results: the frequency of the antigens A23 (p=0.003, RR=3.69), B18 (p<0.0001, RR=3.57), and DR11 (p<0.0001, RR=6.18) was statistically increased in the patients population compared with the healthy controls. Although there is no any significant correlation between HLA antigens and different clinical subsets of scleroderma, antigens B18 and DR11 could be associated with more severe clinical features. Conclusions: the presence of a significant association between SSc and specific HLA antigens (A23, B18, and DR11) could link the HLA system with SSc

Lava flow hazard at Fogo Volcano, Cabo Verde, before and after the 2014–2015eruption

Abstract. Lava flow simulations help to better understand volcanic hazards and may assist emergency preparedness at active volcanoes. We demonstrate that at Fogo Volcano, Cabo Verde, such simulations can explain the 2014–2015 lava flow crisis and therefore provide a valuable base to better prepare for the next inevitable eruption. We conducted topographic mapping in the field and a satellite-based remote sensing analysis. We produced the first topographic model of the 2014–2015 lava flow from combined terrestrial laser scanner (TLS) and photogrammetric data. This high-resolution topographic information facilitates lava flow volume estimates of 43.7 ± 5.2 × 106 m3 from the vertical difference between pre- and posteruptive topographies. Both the pre-eruptive and updated digital elevation models (DEMs) serve as the fundamental input data for lava flow simulations using the well-established DOWNFLOW algorithm. Based on thousands of simulations, we assess the lava flow hazard before and after the 2014–2015 eruption. We find that, although the lava flow hazard has changed significantly, it remains high at the locations of two villages that were destroyed during this eruption. This result is of particular importance as villagers have already started to rebuild the settlements. We also analysed satellite radar imagery acquired by the German TerraSAR-X (TSX) satellite to map lava flow emplacement over time. We obtain the lava flow boundaries every 6 to 11 days during the eruption, which assists the interpretation and evaluation of the lava flow model performance. Our results highlight the fact that lava flow hazards change as a result of modifications of the local topography due to lava flow emplacement. This implies the need for up-to-date topographic information in order to assess lava flow hazards. We also emphasize that areas that were once overrun by lava flows are not necessarily safer, even if local lava flow thicknesses exceed the average lava flow thickness. Our observations will be important for the next eruption of Fogo Volcano and have implications for future lava flow crises and disaster response efforts at basaltic volcanoes elsewhere in the world