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Objectives Survival and death prognostic factors of SSc patients varied during the past decades. We aimed to update the 5- and 10-year survival rates and identify prognostic factors in a multicentre cohort of Italian SSc patients diagnosed after 2009. Material and methods Patients who received a diagnosis of SSc after 1 January 2009 and were longitudinally followed up in four Italian rheumatologic centres were retrospectively assessed up to 31 December 2020. Overall survival of SSc patients was described using the Kaplan–Meier method. Predictors of mortality at 10-year follow-up were assessed by the Cox regression model. A comparison of our cohort with the Italian general population was performed by determining the standardized mortality ratio (SMR). Results A total of 912 patients (91.6% females, 20% dcSSc) were included. Overall survival rates at 5 and 10 years were 94.4% and 89.4%, respectively. The SMR was 0.96 (95% CI 0.81, 1.13), like that expected in the Italian general population. Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) associated with pulmonary hypertension (PH) significantly reduced survival (P Conclusions In the past decade, SSc patients have reached similar mortality of that expected in the Italian general population. Male gender, diffuse cutaneous involvement, comorbidities and PAH with or without ILD represent the main poor prognostic factors.

BACKGROUND/OBJECTIVES: Several scoring systems have been specifically developed for risk stratification in COVID-19 patients. DESIGN: We compared, in a cohort of confirmed COVID-19 older patients, three specifically developed scores with a previously established early warning score. Main endpoint was all causes in-hospital death. SETTING: This is a single-center, retrospective observational study, conducted in the Emergency Department (ED) of an urban teaching hospital, referral center for COVID-19. PARTICIPANTS: We reviewed the clinical records of the confirmed COVID-19 patients aged 60 years or more consecutively admitted to our ED over a 6-week period (March 1st to April 15th, 2020). A total of 210 patients, aged between 60 and 98 years were included in the study cohort. MEASUREMENTS: International Severe Acute Respiratory Infection Consortium Clinical Characterization Protocol-Coronavirus Clinical Characterization Consortium (ISARIC-4C) score, COVID-GRAM Critical Illness Risk Score (COVID-GRAM), quick COVID-19 Severity Index (qCSI), National Early Warning Score (NEWS). RESULTS: Median age was 74 (67-82) and 133 (63.3%) were males. Globally, 42 patients (20.0%) deceased. All the score evaluated showed a fairly good predictive value with respect to in-hospital death. The ISARIC-4C score had the highest area under ROC curve (AUROC) 0.799 (0.738-0.851), followed by the COVID-GRAM 0.785 (0.723-0.838), NEWS 0.764 (0.700-0.819), and qCSI 0.749 (0.685-0.806). However, these differences were not statistical significant. CONCLUSION: Among the evaluated scores, the ISARIC-4C and the COVID-GRAM, calculated at ED admission, had the best performance, although the qCSI had similar efficacy by evaluating only three items. However, the NEWS, already widely validated in clinical practice, had a similar performance and could be appropriate for older patients with COVID-19.

Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used.A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated.The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36-0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density.Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients.

Background and aims The COVID‐19 pandemic represents a source of stress and potential burnout for many physicians. This single‐site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. Methods This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1‐T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. Results Compared with physicians board‐certified in internal medicine, those board‐certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P

Multidisciplinary team (MDT) discussion is the gold standard in the management of interstitial lung disease (ILD). The rheumatologist is not routinely involved in MDT, even if up to 20% of ILD are related to systemic autoimmune rheumatic diseases (SARD). The study aims to assess the agreement and its variation over time between rheumatologists and pulmonologists in the screening of SARD and between rheumatologists and an MDT extended to rheumatologists (eMDT) in evaluating the progression of SARD. We computed the agreement between the pulmonologist and rheumatologist in the identification of red flags for SARDs of 81 ILD cases and between the rheumatologist alone and eMDT in the confirmation of 70 suspected SARD-ILD progressions. The agreement between rheumatologists and pulmonologists was moderate for the detection of autoimmunity test positivity (&kappa, = 0.475, p &lt, 0.001) and family history of SARD (&kappa, = 0.491, p &lt, 0.001) and fair for the identification of extrapulmonary symptoms (&kappa, = 0.225, p = 0.064) or routine laboratory abnormalities consistent with SARD. The average agreement between the rheumatologist and eMDT in the identification of ILD progression was moderate (&kappa, = 0.436, p &lt, 0.001). The class of agreement improved from the first to the third semester. The average agreement with the rheumatologist ranged from fair to moderate, suggesting that a shared evaluation of SARD-ILD in eMDT could improve the diagnostic work-up and the evaluation of ILD progression.

Importance Interleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objective to describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. Design Observational clinical cohort study. Setting Fondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. Participants Patients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio Main outcomes and measures We describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. Results Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevance IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety. Key points Question SARS-CoV-2 infection remains a disease with many unknown aspects for which there are no therapies with proven efficacy. To date, it is recognized that COVID-19 disease may lead to the development of a cytokine storm for which drugs as IL-6R inhibitors may have beneficial effect. Findings In this observational clinical study, we reported the efficacy and safety of intravenous Sarilumab use in SARS-CoV-2 severe pneumonia with a global resolution rate of 83.0% (89.7% in medical wards and 64.3% in ICU) and an overall mortality rate of 5.7%. Meaning IL-6R-inhibition is an effective approach for severe SARS-CoV-2 pneumonia and intravenous Sarilumab is a promising treatment approach leading to an important clinical benefit and good safety in the short term.

LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15986

Background Multidisciplinary Team (MDT) meetings are the current “gold standard” in interstitial lung disease (ILD) diagnosis. Requisite participants are respiratory physicians, radiologists and pathologists. A rheumatologist physician is not routinary involved in MDT even if up to 20% of ILD are related to connective tissue disease, rheumatoid arthritis or systemic vasculitis. Objectives The aim of this study is to evaluate the prevalence and predictors of systemic rheumatological diseases in a cohort of patients with ILD, evaluated by a rheumatology specialist on the advice of MDT in a university hospital. Methods Thirty-two patients with ILD, evaluated at dedicated MDT were referred to a rheumatologist in 2018, usually for autoantibodies positivity or clinical history suspected for a rheumatological disorder. Rheumatologic evaluation included physical examination, routinary blood and urine tests, serum levels of C3 and C4, ANA, Rheumatoid Factor (RF), ANCAs, anti-Sm, anti-RNP, anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-Jo1, anti-dsDNA and anti-CCP antibodies. Family history of autoimmune diseases, presence of rheumatologic red flags (Raynaud’s phenomenon, photosensitivity, inflammatory skin manifestations, sicca syndrome, recurrent fever, inflammatory arthralgias, paresthesias, oral or genital aphthosis, thrombosis and recurrent miscarriages), respiratory symptoms and pulmonary function test were also evaluated. When indicated, capillaroscopy, joint imaging and salivary gland biopsy were performed. Results Twenty-one patients (65.6%) were female. At the time of rheumatological evaluation, the patients had a mean age of 64.4±12.6 years with a mean period of 21.1±39.6 months since the first identification of ILD on a CT scan. Twenty-five (78.1%) and 18 (56.3%) patients respectively complained exertional dyspnea and cough, 6 patients (18.8%) were on oxygen therapy and 13 (40.6%) had a FVC Conclusion Single clinical or laboratory abnormalities are not strongly associated to a rheumatological diagnosis in patients with ILD, suggesting that only a comprehensive rheumatological evaluation allows correct classification of the disease associated with ILD and is mandatory to make or exclude a diagnosis. In this study, we evaluated only preselected patients by ILD-MDT, but the results indirectly suggest that direct participation of rheumatologist to MDT is advisable to increase accuracy and reduce delay in diagnosis and treatment. Disclosure of Interests: Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Lucrezia Verardi: None declared, Silvia Laura Bosello: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer

Background Interstitial lung d isease (ILD) is the leading cause of death in Systemic Sclerosis (SSc) but its pathogenesis is not fully understood. Esophageal disease is common in SSc and micro aspiration of both acid and non-acid gastroesophageal reflux could be involved in the pathogenesis of ILD. Esophagogastroduodenoscopy (EGD) is an essential tool to evaluate disease severity of upper gastrointestinal tract involvement in SSc. Objectives The objective of the present study is to assess the role of EGD in predicting pulmonary functional deterioration in SSc patients. Methods One hundred and fifty patients with SSc and suspected esophageal involvement underwent EGD. Pulmonary function tests were performed at baseline and after a 36-months follow-up. Patients were characterized for disease phenotype, BMI, smoking exposure and medication history. A significant ILD progression was defined as a relative decline >= 10% of FVC or a concomitant decline >= 5% of FVC and >= 15% of DLCO. Results One hundred and thirty-six patients (90.5%) were female with a mean age of 55.6 ± 13.8 years and 12.1% were active smokers. Fifty patients (33.3%) had a diffuse cutaneous disease; 37.4% and 40.8% were positive for anti-centromere and anti-Scl70 antibodies respectively. The mean disease duration from the first non-Raynaud symptom was 5.9±6.7 years. Sixty-one patients (40.8%) showed EGD signs of reflux esophagitis. Among them, 31.3% had an erosive form (9.5% grade A, 15.6% grade B, 4.8% grade C and 1.4% grade D according to Los Angeles classification). At the baseline, 23.1% of the patients had a FVC Conclusion SSc patients with erosive esophagitis present a higher risk of progression of interstitial lung disease. This evidence supports a role of micro-aspiration of gastric contents in the development of inflammation and fibrosis of the airways. Disclosure of Interests Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Lucrezia Verardi: None declared, Umberto La Porta: None declared, Giovanni Battista Canestrari: None declared, Ludovica Berardini: None declared, Silvia Laura Bosello: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer

Background:Pulmonary involvement is the main determinant of disease-related mortality in systemic sclerosis (SSc). The SENSCIS and INBUILD trials have documented the efficacy of the antifibrotic drug Nintedanib (NTN) in the treatment of SSc-related interstitial lung disease (SSc-ILD) and progressive forms of ILD other than Idiopathic Pulmonary Fibrosis1,2. The criteria for the use of this drug in patients with SSc-ILD in clinical practice are currently being defined.Objectives:To evaluate the proportion of patients eligible for NTN treatment based on the enrollment criteria fof the SENSCIS and INBUILD studies in a real-life cohort of SSc-ILD patients.Methods:We considered consecutive patients with ILD extension on CT ≥10% and disease duration ≤7 years with at least one visit in the period between September 2016 and December 2019. Data of the clinical visits were retrospectively evaluated. For each patient, we examined the visits during which a well-tolerated immunosuppressive therapy was modified because of progression of SSc-ILD and the most recent follow-up visit. Eligibility of patients for NTN was defined according to the inclusion criteria of the SENSCIS and INBUILD trials. Patients with more than 2 acral ulcers at the time of evaluation, history of digital amputation, pulmonary hypertension (functional class III-IV) and increased hemorrhagic or thrombotic risk were judged not eligible to NTN in trials.Results:A total of 177 visits regarding 78 patients were examined (females 80.8%, diffuse skin disease 51.3%, anti-Scl70 antibodies positivity 55.7%, age 54.8±16.0 years, disease duration 4.0±2.4 years). Considering the visits in which indication for a therapeutic change was given, 54 patients (54.5%) were eligible for NTN according to SENSCIS criteria and of these 31 (31.3%) also according to INBUILD criteria (Figure 1). In this group, 25 patients were treated with mycophenolate mofetil, 11 with azathioprine, 10 with cyclophosphamide, 7 with methotrexate and 8 with rituximab (2 in combination). At the latest available evaluation, 42 patients (62.8%) were eligible for NTN according to SENSCIS criteria and of these 12 (15.4%) also according to INBUILD criteria (Figure 1). In this group, 30 patients were in mycophenolate mofetil (6 in combination with biologic treatment), 5 in azathioprine, 1 in cyclophosphamide, 1 in methotrexate, 6 in rituximab, 2 in tocilizumab and 1 in pirfenidone. Overall, the factors limiting NTN start according to the trial enrollment criteria would have been: uncompromised (19.2%) or too low (6.4%) DLco values, too low FVC (3.4%), severe acral disease with ulcers (16.9%), severe pulmonary arterial hypertension (6.2%), increased thrombotic or haemorrhagic risk (6.2%). In the scenario of eligibility, skin progression was detectable in 43.4% of all visits.Conclusion:Treatment that can modify the progression of SSc-ILD are currently limited. Based on our retrospective analysis, the use of NTN in accordance with current clinical evidence could be considered in a significant percentage of patients with SSc-ILD.References:[1]Flaherty KR, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019.[2]Distler O, et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019.Disclosure of Interests:None declared

Background:An increased incidence of cancer in patients with systemic sclerosis (SSc) is well-established1. Current knowledge about the onco-transforming power of immunosuppressive treatments in both non-rheumatological and rheumatological pathologies, suggests an increased incidence of hematological and solid neoplasms2. Evidences on the possible role of the immunosuppressants in the onset of cancer during SSc are lacking.Objectives:To evaluate the incidence of malignancies in SSc patients exposed to immunosuppressive therapy.Methods:The incidence of neoplasia in a cohort of 600 patients with SSc was evaluated retrospectively. Patients diagnosed with malignancy within 36 months from SSc onset were excluded from the analysis since suspected for paraneoplastic form. Patients exposed to methotrexate, cyclophosphamide, azathioprine and mycophenolate were confronted with a group comparable for age at onset, sex, disease variant, autoantibodies and exposure to other disease-specific therapies, using propensity score matching analysis. The considered follow-up was between the clinical onset and the diagnosis of cancer or the last available visit or the twenty-fifth year of illness.Results:The analysis was carried out on 526 patients observed for an average period of 12.1 ± 6.0 years (males 9.5%, age at onset 49.0 ± 15.3 years); 24.9% had diffuse cutaneous variant of the disease and 39.0% and 34.8% were respectively positive for anti-centromere and anti-Scl70 antibodies. During the follow-up, 19.0% of patients were exposed to cyclophosphamide, 15.3% to azathioprine, 14.4% to methotrexate and 11.6% to mycophenolate mofetil. Sixty-five cancer diagnoses were made after the 36th month from onset (incidence 1.02: 100 patients/year), comprising 16 mammary cancers, 12 cancers of the gastro-intestinal tract, 11 cancers of the head-neck area, 10 cancers of the lungs, 9 cases of skin-cancer, 5 haematological malignancies and 1 brain tumour. The incidence of cancers did not differ in relation to treatment with cyclophosphamide (X2 = 0.001, p = 0.961), azathioprine (X2 = 2.141, p = 0.143), mycophenolate mofetil (X2 = 0.001, p = 0.993) or methotrexate (X2 = 0.920, p = 0.337) (Figure 1).Conclusion:Our data are consistent with an increased incidence of neoplasms in the course of SSc, with a rate that appears almost doubled compared to the general Italian population with similar sex and age distribution (0.55: 100 patients/year; Italian Association of Tumor Registries data3). In our SSc cohort this risk is independent of exposure to immunosuppressive drugs commonly used for the treatment of scleroderma disease.References:[1]Akira O et al. Cancer Incidence in Systemic Sclerosis: Meta-Analysis of Population-Based Cohort Studies. Arthritis & Rheumatism. 2013[2]Zitvogel L et al. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol. 2006[3]Registri Tumori di popolazione in Italia: la Banca Dati AIRTUM (Associazione Italiana Registri Tumori). 2020Disclosure of Interests:None declared

Objective Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients. Methods We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered. Results We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P = .027) and micro-thrombosis (P, Highlights • We assessed and accurately described peripheral microvasculature in COVID-19 patients through nailfold videocapillaroscopy. • Capillary alterations at the nailfold bed suggest a broad COVID-related microvascular involvement. • Different alterations in acutely-ill and recovered patients resemble a transition from acute to post-acute injury.

Background:Systemic Sclerosis (SSc) is characterized by an increased incidence of macro- and microvascular complications. Current evidences on efficacy, safety and tolerability of acetylsalicylic acid (ASA) in SSc patients are limited, and the indication to this treatment is based on the experience of each single centre or physician. Esophagus and stomach are the portions of the digestive tract that are more frequently affected by adverse events due to ASA exposure.Objectives:We evaluated the incidence of adverse events associated with low-dose ASA treatment in a cohort of patients affected by SSc.Methods:Demographic data and disease features of 302 patients affected by SSc treated with low-dose ASA were collected and patients were followed-up for a median period of 6.9 years (range: 0-20 years). The proportion of patients taking ASA for secondary prevention for cardiovascular disease was also noted. The incidence of discontinuation of the drug, gastrointestinal intolerance, bleeding and death in the observation period was recorded.Results:Patients had a median age of 54.0 years (19.6-89.4); 91.9% were female, 13.2% were smokers and 44.0% had a BMI≥30Kg/m2. The prevalence of ischemic heart disease, peripheral vascular disease and stroke was of 8.6%, 5.3% and 3.3%, respectively; 48.7% of the patient took ASA in primary cardiovascular prevention. Therapy started after a median disease duration of 4.8 years (range: 0.0- 30.1 years) since the first non-Raynaud symptom and 56.6% of patients had an early disease (less than three years of disease duration). During the observation period, 30 patients (14.3 per 1000 person-years) discontinued ASA after an average period of assumption of 4.6 years (range: 0.3-18.0 years). The main adverse events were heartburn, dyspepsia and hematochezia, recorded in 18 patients (8.6 per 1000 person-years). Eight of them (3.8 per 1000 person-years) had evidence of digestive tract bleeding. Five patients (2.4 per 1000 person-years) discontinued ASA due to recurrent epistaxis. Twenty-eight patients (13.4 per 1000 person-years) died in the follow-up period, 16 of these (7.6 per 1000 person-years) because of SSc-related causes. None of them had evidence of major bleeding. We used Kaplan-Meier analysis to evaluate the incidence of ASA discontinuation. The history of digital ulcers (Log rank test X24.7, p=0.037) and male sex (Log rank test X24.3, p=0.03) were associated with a higher cumulative ASA discontinuation rate due to gastrointestinal intolerance.Conclusion:In our cohort of SSc patients, ASA resulted safe and well tolerated in most cases, despite the risk of gastroesophageal abnormalities due to disease. Although this comforting results, taking in account the lack of controlled-randomized trials about efficacy and safety, the choice to start antiplatelet therapy with ASA should be mandatorily preceded by a careful evaluation of risks and benefits. Furthermore, an attentive monitoring for possible adverse effects is needed during ASA treatment. Patients with digital ulcers and male sex could present less drug tolerability.References:[1]Valentini G et al. Ann Rheum Dis 2019. Beckett VL et al. Arthritis Rheum 1984. Kavian N et al. Vascul Pharmacol 2015. Lavie CJ et al. Curr Probl Cardiol 2017.Disclosure of Interests:Lucrezia Verardi: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Umberto La Porta: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer

Background:Systemic sclerosis (SSc) is one of the connective tissue diseases with the poorer prognosis and disease-related causes, particularly pulmonary fibrosis, PAH and cardiac involvement, accounting the most deaths.Objectives:This multicentre study aimed to evaluate the global survival and any predictor of mortality in a large multicentric cohort of SSc patients.Methods:We performed a retrospective analysis examining the medical records of our longitudinal SSc cohorts with a median (IQR) follow-up of 11 (6-18) years from 3 Scleroderma Units since January 2009. All clinical, laboratory and instrumental findings have been recorded and analyzed using Chi-squared tests, Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models.Results:Data from 750 SSc patients (91.9% female; mean (SD) age at first Non-Raynaud symptom 48.4 (15.3) years, median (IQR) disease duration 3 (0-8) years; diffuse cutaneous involvement 162 (21.6%) patients) fulfilling the 1980 ARA and/or 2013 ACR/EULAR classification criteria, were collected. All patients were positive for ANA, anti-Topo-I Abs were found in 235 (31.3%) and Cenp-B Abs in 300 (40%) patients. 98 (13.1%) patients were positive to other Abs (Anti-RNA polymerase III, anti-Pm/Scl) and anti-ENA were negative/unknown for 117 (15.6%) patients. Interstitial lung disease (ILD) was present in 202 (26.9%), pulmonary arterial hypertension (PAH) was found in 29 (3.9%), and 50/750 (6.7%) patients presented pulmonary hypertension combined with ILD (PH-ILD). The overall 10-years survival was 93.1% and, it was significantly impaired by the presence of ILD, PAH or PH-ILD [Figure]. The univariate analysis showed that female gender, higher age at first Non-Raynaud symptom, earlier referral to a tertiary Scleroderma center, absence of any ENA antibodies, and PH-ILD presence were survival predictors. After multivariate analysis the significance of PH-ILD was lost [Table]. Disease duration, basal Rodnan skin score, smoking, renal or gastrointestinal comorbidities, NYHA functional class, steroid or immune-suppressive treatments did not reach the statistically significance.Conclusion:Our study demonstrated a global 10-years survival rate over 93%. Male patients and rapid evolution of Non-Raynaud symptoms represent the main death predictors in our SSc cohort. A rapid referral to a tertiary rheumatological centre and early treatment with effective agents are associated to a better prognosis.Figure.Kaplan-Meier curves for 5-years survival in SSc patients (Log-rank 8.96, p=0.03).Table.Prognostic factors for 10-years survival at univariate and multivariate analysis.UNIVARIATE ANALYSISMULTIVARIATE ANALYSISHR95%ICPHR95%ICPFemale gender0.350.15-0.810.010.310.15-0.660.002Age at first Non-Raynaud symptom1.071.04-1.10.0011.081.05-1.110.001Time referral to a tertiary SSc centre0.830.76-0.920.0010.840.77-0.930.001Absence of any ENA antibodies0.080.01-0.620.010.090.01-0.710.02PH-ILD presence2.61.01-6.820.042.40.93-6.10.069Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Enrico De Lorenzis: None declared, Addolorata Corrado: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Marco Fornaro: None declared, Fabio Montini: None declared, Livio Urso: None declared, Lucrezia Verardi: None declared, Alberto Altomare: None declared, Francesco Paolo Cantatore: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD

Background Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc) but its pathogenesis and the risk factors of pulmonary function deterioration are not fully understood. Esophageal disease is high frequent in SSc and motor activity abnormalities with occult micro-aspiration of both acid and non-acid gastro oesophageal reflux has been implicated in the pathogenesis of ILD. DLCO reduction is considered the earliest sign of microaspiration-induced lung damage1. Cross-sectional studies have demonstrated an association of SSc-ILD and esophageal abnormalities on 24 hours intraesophageal pH-monitoring and esophageal manometry but prospective evaluation of lung deterioration is lacking2,3. Esophagogram was proposed as a useful tool to evaluate disease severity of upper gastrointestinal tract involvement in SSc4. Objectives To assess the role of esophagogram in predicting pulmonary function test deterioration in SSc-patients. Methods We retrospectively evaluated 160 consecutive SSc patients who underwent esophagogram because of suspected upper gastro-intestinal involvement. All patients underwent baseline pulmonary function tests and global clinical evaluation. Eighty-five patients underwent a High Resolution CT within 3 months from esophagogram because of suspected lung involvement. One hundred twenty three patients underwent pulmonary function test every 6 months up to 24 months. Results Seventy five patients (46.9%) presented abnormalities of peristaltic waves, 50 patients (31.2%) showed structural changes (hypotonic oesophagus or dilatation) while indirect signs of cardial incontinence (patent cardia or gastro-esophageal reflux) were present in 36 patients (22.5%). A reduced peristaltic activity with a prolongation of transit time was associated to reduced DLCO (50.16%±19.80% vs 60.36±22.69%, p=0.002) and TLC (87.05%±20.43% vs 95.09±20.59%, p=0.017). An hypotonic oesophagus was reported in 25.2% of patients and it was associated to ILD on CT (72.0% vs 28.0%, p=0.033). Patients with hypotonic oesophagus presented a reduced FVC (84.63%±22.86% vs 102.93±21.40%, p Conclusions The esophagogram is wide available, well tolerated and inexpensive tool to assess upper gastro-intestinal tract involvement and its abnormalities are associated to SSc-ILD severity. Because of a faster deterioration of lung function is associated to esophagogram abnormalities, a complete gastro-intestinal evaluation in ILD-SSc patients is mandatory. References [1] Schachter LM, et al. Chest2003. [2] Christmann RB, et al. Semin Arthritis Rheum2010. [3] Marie I, et al. Arthritis Care Res2001. [4] Medsger TA, et al. Clin Exp Rheumatol2003. Disclosure of Interest None declared

Background Gastrointestinal (GI) symptoms are seen in majority of patients with Systemic Sclerosis (SSc) and are a common presenting feature of disease. Severe GI involvement may lead to malabsorption which represents a poor prognostic factor. Accordingly, a regular monitoring of gastrointestinal tract involvement and nutritional status appears crucial in SSc patients. Previous studies reported low values of bone mass density (BMD) in SSc patients1. While no specific relationship has emerged between the two conditions, it’s likely that disease related GI involvement may contribute to the alterations in BMD. Objectives To determine if GI-related clinical status was associated to low bone density in our cohort of SSc patients. Methods Two-hundred-ten unselected SSc patients have been enrolled. The 7-items UCLA SCTC GIT 2.0 questionnaire and Malnutrition Universal Screening Tool (MUST) were administered to each patient. A comprehensive medical history was collected. A blood panel for nutritional status was also performed. T-scores and Z-scores at lumbar spine, femoral neck, Ward’s and total hip measured by dual-energy X-ray absorptiometry (GE Lunar Prodigy) were measured. Results In our cohort, 86.7% of patients reported some GI symptoms. The mean UCLA GIT total score was 0.345±0.34 and 51 patients (24.3%) were at risk of malnutrition according to MUST (score ≥1). 53.7% patients had BMD values Patients with spine T-score Femoral neck T-score On the other hand, the comparison of patients with severe, moderate and mild symptoms according to UCLA GIT total score2 showed an association between progressively lower values of spine and total hip T-score and increasing severity of GI symptoms (ANOVA for spine T-score: p=0.015; for total hip T-score: p=0.048). Patients at risk of malnutrition (MUST score ≥1) presented significant lower T-score for all the considered sections (spine and hip) and significant lower total hip Z-score. Conclusions In our SSc cohort gastrointestinal symptoms were frequent and were associated with low BMD. Considering the heterogeneity of GI involvement, UCLA SCTC GIT 2.0 emerged as a useful and feasible tool to assess GI involvement and other associated comorbidities. In particular, SSc patients who report remarkable GI symptoms and are at risk of malnutrition according to MUST may benefit from a stricter control of BMD to promptly detect osteopenia and osteoporosis. References [1] Omair MA, et al. J Rheumatol. 2013 [2] Khanna D, et al. Curr Opin Rheumatol. 2013 Disclosure of Interest None declared