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BackgroundThe COVID-19 pandemic, with its uncertainties, fears of contagion, mass lockdowns and containment measures, has dramatically impacted on people’s everyday lives leading to an increased risk of mental disorders, particularly Post-Traumatic Stress Disorder (PTSD). Despite evidence in general population and healthcare workers1,2, scant data emerged on vulnerable populations, such as of patients with chronic illness, particularly rheumatic and musculoskeletal diseases (RMDs)3,4, who also underwent difficulties in the management and treatment of their disorders.ObjectivesTo assess PTSD and post-traumatic stress symptoms in a sample of patients with RMDs, during the COVID-19 pandemic in Italy.MethodsPERMAS is a monocentric prospective observational study led by the Rheumatology Unit, the Psychiatric Clinic and the Institute of Management of the School of Advanced Studies. Patients with a RMD diagnosis, were consecutively enrolled from May 2021 to January 2022. During the visit, sociodemographic characteristics and psychopathological data were collected through online survey, whereas clinical data were collected by physician. The survey included the Trauma and Loss Spectrum- Self Report (TALS-SR) and the Impact of Event Scale- Revised (IES-R), aimed to assess symptomatological PTSD and post-traumatic stress symptoms related to the impact of the COVID-19 pandemic.ResultsA total of 194 eligible patients, with a mean age of 50.3±12.17 years, was included: 142 (73.19%) were females; 112 (57.74%) patients reported connective tissue diseases (CTD), 63 (32.47%) arthritis and 19 (9.8%) vasculitis. A total of 33 (17%) subjects reported a symptomatological PTSD by means of the TALS-SR. The prevalence of Partial PTSD (defined by at least 2 out of the 4 criteria for DSM-5 diagnosis of the disorder) was 56.7%, with significant higher rates among females (90, 81.8%) with respect to males (20, 18.2%) (p=.013). Accordingly, a IES-R mean total score of 21.90 ±15.98 was found in the total sample and a gender difference emerged, with higher mean scores among females rather than males (23.42 ±16.26 vs 21.90 ±15.98, p=.031).ConclusionThe present findings point out high prevalence rates of symptomatological PTSD among patients suffering from RMDs, highlighting the potentially traumatic burden of the COVID-19 pandemic in this particular population, especially among females, suggesting the need of further investigations to address tailored prevention and intervention strategies.References[1]Fiorillo A, Sampogna G, Giallonardo V, Del Vecchio V, Luciano M, Albert U, Carmassi C, Carrà G, Cirulli F, Dell’Osso B, Nanni MG, Pompili M, Sani G, Tortorella A, Volpe U. Effects of the lockdown on the mental health of the general population during the COVID-19 pandemic in Italy: Results from the COMET collaborative network. Eur Psychiatry 2020; 63(1), e87.[2]Carmassi C, Dell’Oste V, Bui E, Foghi C, Bertelloni CA, Atti AR, Buselli R, Di Paolo M, Goracci A, Malacarne P, Nanni MG, Gesi C, Cerveri G, Dell’Osso L. The interplay between acute post-traumatic stress, depressive and anxiety symptoms on healthcare workers functioning during the COVID-19emergency: A multicenter study comparing regions with increasing pandemic incidence. J Affect Disord 2022; 298(Pt A), 209-216.[3]Garrido-Cumbrera M, Marzo-Ortega H, Christen L, Plazuelo-Ramos P, Webb D, Jacklin C, Irwin S, Grange L, Makri S, Frazão Mateus E, Mingolla S, Antonopoulou K, Sanz-Gómez S, Correa-Fernández J, Carmona L, Navarro-Compán V. Assessment of impact of the COVID-19 pandemic from the perspective of patients with rheumatic and musculoskeletal diseases in Europe: results from the REUMAVID study (phase 1). RMD 2021; 7(1), e001546. doi: 10.1136/rmdopen-2020-001546[4]Wang XA, Duculan R, Mancuso CA. Coping Mechanisms Mitigate Psychological Stress in Patients With Rheumatologic Diseases During the COVID-19 Pandemic. J Clin Rheumatol 2021. doi: 10.1097/RHU.0000000000001757Disclosure of InterestsGiovanni Fulvio: None declared, Virginia Pedrinelli: None declared, Gianni Andreozzi: None declared, Francesca Trentin: None declared, Sara Fantasia: None declared, Silvia Fonzetti: None declared, Chiara Fustini: None declared, Mattia Da Rio: None declared, Gabriele Cappellato: None declared, Cosimo Cigolini: None declared, Davide Schilirò: None declared, Michele Maffi: None declared, Laura Scagnellato: None declared, Anastasiya Valevich: None declared, Federico Fattorini: None declared, Inmaculada Concepción Navarro García: None declared, Ilaria Palla: None declared, Valentina Lorenzoni: None declared, Andrea Gaglioti: None declared, Claudia Carmassi: None declared, Chiara Tani: None declared, Giuseppe Turchetti: None declared, Liliana Dell’Osso: None declared, Marta Mosca Speakers bureau: Lillly, Astra Zeneca, GSK, Consultant of: Lillly, Astra Zeneca, GSK

The aim of this study was the characterization of constitutive and induced defense mechanisms in the bark tissues of

The aim of this study was the characterization of constitutive and induced defence mechanisms in the bark tissues of Cupressus sempervirens before and after infection with the bark fungus Seiridium cardinale that is responsible for Cypress Canker Disease. The time-course development of polyphenolic parenchyma cells (PP cells) and phloem axial resin ducts PARDs(PARD) like structures in the phloem was investigated in two C. sempervirens clones, one resistant and one susceptible to the disease, through anatomycal and hystologycal observations carried out by light microscope during a 19 days trial. PP cells were constitutively more abundant in the canker resistant clone compared to the susceptible clone, while PARDsPARD-like structures were not present in the bark of untreated plants of both clones. PP cells increased in both clones as a response to infection, but in the resistant clone they were more abundant 5 and 12 days after inoculation. Following inoculation, PARDsPARD-like structures appeared in the phloem after 5 days in the resistant clone and only after 12 days in the susceptible clone. Even the number of secretory cells(surrounding the PARDsPARD-like structures) was higher in the R clone 5 and 12 days after inoculation compared to the S clone. These observations demonstrate a faster phloem response of the resistant clone in the early phase of the infection. This may slow down initial growth of the fungus contributing to the resistance mechanism.

BackgroundManagement of the health emergency caused by COVID-19 pandemic majorly disrupted the delivery of healthcare services to patients with chronic conditions like Systemic Autoimmune Diseases (SAD), both because resources were mainly channeled towards the care of infected patients, but also because patients tended to avoid seeking medical care for fear of becoming infected. PER-MAS is a 2-year project aimed at assessing the clinical, psychopathological, and socio-economic impact of COVID-19 in a cohort of patients with SAD.ObjectivesTo assess the impact of COVID-19 pandemic on drug withdrawal, disease flares and hospitalizations for disease exacerbation in a cohort of patients with SAD through an interim analysis of data from the PER-MAS project.MethodsA sample of 214 consecutive patients was recruited in a reference center for rare and complex autoimmune diseases from April 2021 to January 2022. Inclusion criteria were definite diagnosis of SAD (Connective Tissue Disease (CTD), Inflammatory Arthritis (IA) or Vasculitis), regular follow-up and at least 2 years of disease. Patients were asked to fill out an extensive self-administered questionnaire on disease activity and healthcare resource use during the pandemic (March 2020-moment of assessment). Pre-pandemic (March 2019-February 2020) and early pandemic (March 2020-February 2021) clinical data were recorded through retrospective chart review and patient interview.ResultsAt enrolment, 119 patients were affected by CTDs (55.6%), 71 by IA (33.18%), 24 by vasculitis (11.21%), with mean age 50.44± 12.97, and mean disease duration 11.17 ± 8.94. 30.37% took steroids, 39.7% hydroxychloroquine, 61.68% DMARDs, and 9.3% vasoactive drugs.Overall, disease course was similar in pre-pandemic and early pandemic phase: in the first period, rheumatologic condition was stable in 57.35% of patients, persistently active in 27.3% and 35.61% had ≥ 1 episode of disease exacerbation (mean 0.665±1.15, range 0-6); in the second period, 60.56% of patients was stable, 24.88% persistently active, and 39.44% had ≥1 exacerbation (mean 0.49 ±0.77, range 0-4). Mean number of visits (2.56±2.57 and 2.61±2.79), hospitalizations (0.168±0.698 and 0.14±0.473, p=0.6), number of patients with outpatient visits=0 (7.47 vs 7%), and number of patients with ≥ 1 hospital admission (10.28 vs 11.6%) were also similar, while the number of patients with hospital admissions for disease exacerbation was significantly higher in the second period (6.1 vs 11.21%, p=0.001).170 patients completed the survey: from March 2020 to enrolment, 18.2% suspended ≥1 anti-rheumatic drug (6.25% of them for fear of contracting COVID-19 disease, 15.6% for difficulty in obtaining medications), 20% self-managed ≥ 1 disease exacerbation, and 40% had ≥ 1 telemedicine consult. From March to July 2020, 41.76% had their visit rescheduled (35.23% for hospital access restrictions, 5.3% for travel restrictions, 1.17% for fear). Conversely, only 14.7% of patients had their visit rescheduled (8.23% for hospital access restrictions, 4.7% for other reasons) from July 2020 to enrolment.ConclusionIn the early pandemic phase, overall disease course was similar to the pre-pandemic phase, but we observed an increase in the number of patients with ≥ 1 hospitalization for disease. Moreover, despite our efforts, patients reported a non-negligible rate of drug discontinuation for non-medical indication and difficulty to get access to rheumatologic consultation, highlighting the need of alternative organizational models in case of future pandemics.AcknowledgementsGiulia Sacco for helping in patient recruitment and data management.Disclosure of InterestsFrancesca Trentin: None declared, Giovanni Fulvio: None declared, Gianni Andreozzi: None declared, Cosimo Cigolini: None declared, Mattia Da Rio: None declared, Valerio Dell’Oste: None declared, Elena Elefante: None declared, Federico Fattorini: None declared, Silvia Fonzetti: None declared, Valentina Lorenzoni: None declared, Michele Maffi: None declared, Inmaculada Concepción Navarro García: None declared, Ilaria Palla: None declared, Virginia Pedrinelli: None declared, Laura Scagnellato: None declared, Davide Schilirò: None declared, Anastasiya Valevich: None declared, Andrea Gaglioti: None declared, Claudia Carmassi: None declared, Chiara Tani: None declared, Liliana Dell’Osso: None declared, Giuseppe Turchetti: None declared, Marta Mosca Speakers bureau: Lilly, Astra Zeneca, GSK, Consultant of: Lilly, Astra Zeneca, GSK

BackgroundBelimumab (BEL) is approved for the treatment of active autoantibody-positive systemic lupus erythematosus (SLE).1 Four Phase 3 studies have consistently demonstrated greater SLE Responder Index (SRI) response rates with BEL vs placebo (PBO).2-5 This robust dataset allows for additional exploration of the onset of efficacy of BEL and response rates by patient (pt) characteristics.ObjectivesTo perform a post hoc analysis evaluating the effect of BEL on SRI-4 response across a large, pooled population and pt subgroups.MethodsThe Belimumab Summary of Lupus Efficacy (Be-SLE) integrated analysis evaluated data from adults with SLE from 5 double-blind, PBO-controlled BEL trials: BLISS-76, BLISS-52, BLISS-NEA, BLISS-SC, and EMBRACE.2-6 Pts were randomised to BEL (monthly intravenous 10 mg/kg or weekly subcutaneous 200 mg) or PBO, plus standard therapy. Data were collected every 4 weeks (wks) from baseline (BL) to Wk 52. The SRI-4 response rate (a composite measure that includes ≥4-point reduction in Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index [SELENA-SLEDAI] score, stable Physician Global Assessment [PGA] increase of ResultsOverall, 3086 pts were included (BEL, n=1869; PBO, n=1217). Most were female (94.4%); mean (standard deviation [SD]) age was 37.0 (11.6) years. Mean (SD) SLE duration was 6.4 (6.4) years.At Wk 52, in the overall population, significantly more BEL vs PBO pts were SRI-4 responders (Figure 1). A significantly greater proportion of SRI-4 responders was observed with BEL vs PBO as early as Wk 8 (38.4% vs 33.3%; odds ratio, OR [95% confidence interval, CI] 1.25 [1.07, 1.46]; p=0.0060), which continued to increase to Wk 52 (54.8% vs 41.6%; OR [95% CI] 1.70 [1.46, 1.98]; pFigure 1.SRI-4 response at Wk 52 in the overall population and by BL characteristic subgroups.*OR (95% CI) and p-value are from a logistic regression model for BEL vs PBO comparison with covariates of treatment group, study and BL SELENA-SLEDAI score (≤9 vs ≥10)SRI-4 response rates were significantly higher with BEL vs PBO in most subgroups, with the highest response rates observed in pts with SELENA-SLEDAI score of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml, and low C3 and/or C4 at BL (Figure 1).ConclusionSignificantly more pts receiving BEL had SRI-4 response rates that occurred from Wk 8 and were maintained through Wk 52 compared with pts receiving PBO. The efficacy of BEL was consistent across multiple pt subgroups, with higher response rates in pts with SELENA-SLEDAI scores of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml and low C3 and/or C4 at BL. These results further substantiate the benefits of BEL in the treatment of adults with SLE.References[1]GlaxoSmithKline. Benlysta US prescribing information. 2021[2]Furie R, et al. Arthritis Rheumatol 2011;63(12):3918–30[3]Navarra SV, et al. Lancet 2011;377(9767):721–31[4]Stohl W, et al. Arthritis Rheum 2017;69(5):1016–27[5]Zhang F, et al. Ann Rheum Dis 2018;77(3):355–63[6] Ginzler E, et al. Arthritis Rheum 2021; doi: 10.1002/art.41900AcknowledgementsThis analysis was funded by GlaxoSmithKline (GSK). Medical writing support was provided by Lulu Hill, MPharmacol, Fishawack Indicia Ltd. UK, part of Fishawack Health, and was funded by GSK.Disclosure of InterestsMichelle A Petri Consultant of: GSK, Grant/research support from: GSK, George Bertsias Speakers bureau: Pfizer, Aenorasis, UCB, Novartis, Lilly, SOBI, Consultant of: Novartis, GSK, AstraZeneca, Grant/research support from: GSK, Pfizer, Mark Daniels Shareholder of: GSK, Employee of: GSK, Norma Lynn Fox Shareholder of: GSK, Employee of: GSK, Bevra H. Hahn Consultant of: UCB, GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Julia Harris Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, Chiara Tani Speakers bureau: GSK, AstraZeneca, Anca Askanase Consultant of: AstraZeneca, Aurinia Pharmaceuticals Inc., Amgen, AbbVie Inc., BMS, GSK, Grant/research support from: AstraZeneca, Eli Lilly and Company, GSK, Idorsia Pharmaceuticals Ltd, Janssen Pharmaceuticals, Pfizer

BackgroundAntiphospholipid Syndrome (APS) is a rare autoimmune disease characterized by thrombotic events and/or pregnancy morbidities in the presence of confirmed positivity for antiphospholipid antibodies (aPL). Complement was demonstrated to be involved in aPL-related pregnancy loss in animal models and several groups investigated the significance of complement levels in human disease. C3 and C4 serum levels were assessed in several cohorts of pregnant patients with APS and/or aPL positivity in order to relate complement consumption with adverse pregnancy outcome (APO).According to some authors, hydroxychloroquine (HCQ) can control the activation of the complement system, improve pregnancy outcome and reduce aPL title.ObjectivesThis study was designed to verify the effect of HCQ in addition to low dose aspirin (LDA) + low molecular weight heparin (LMWH) treatment in a multicenter cohort of primary APS (PAPS) and aPL carriers pregnant women and the possible correlation with preconception serum C3/C4 levels.MethodsMedical records of pregnant women with confirmed positivity for aPL antibodies attending twelve referral centers from January 2010 to December 2020 were retrospectively evaluated. We considered as aPL-related APO: spontaneous abortions (ResultsWe have analyzed 164 singleton PAPS/aPL carrier pregnancies (22 aPL carriers - 13%) in 128 patients: all were treated with combination therapy (LDA+LMWH), and in 30 HCQ was added. 58 pregnancies (43%) had low levels of preconception C3/C4. A triple aPL positivity was observed in 54 pregnancies, 14 of them were treated with combination therapy + HCQ. When considering the whole cohort, the addition of HCQ had not significantly improved the gestational outcome. Further stratification was performed on the basis of complement consumption. In the group of patients with preconception low C3/C4 levels the addition of HCQ had not significantly improved pregnancy outcome. We have lastly evaluated 40 pregnancies with a high-risk profile (triple aPL positivity and complement consumption), in which we have found that HCQ significantly improved gestational outcome (p=0.018, Table 1).Table 1.Relationship between APO, therapy during pregnancy and risk profile.All pregnancies (n=164)Reduced C3/C4 (n=58)Triple aPL+ and reduced C3/C4 (n=40)LDA+LMWH (n, %)LDA+LMWH+HCQ (n, %)pLDA+LMWH (n, %)LDA+LMWH+HCQpLDA+LMWHLDA+LMWH+HCQp(n, %)(n, %)(n, %)APO62 (46%)16 (53%)ns32 (68%)4 (36%)ns23 (77%)3 (30%)0.018No APO72 (54%)14 (47%)15 (32%)7 (64%)7 (23%)7 (70%)Total1343047113010This observation could not be confirmed in patients with single or double aPL positivity.ConclusionThe study shows that administering HCQ in addition to combination therapy can improve gestational outcome in aPL/PAPS high-risk patients. This observation confirms that HCQ exerts a beneficial effect on aPL pregnancies by complement inhibition as it was shown in animal models. In addition, our results provide the clinicians a useful tool to implement conventional treatment in patients at high risk of pregnancy complication or loss.References[1]De Carolis S, et al. Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment? Autoimmun Rev 2015;14:760-2.[2]Mekinian A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in antiphospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 2015;40:498-502.[3]Mekinian A et al. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome? Autoimmun Rev 2015;14:23-9.Disclosure of InterestsNone declared

BackgroundSystemic lupus erythematosus (SLE) is a heterogeneous disease which can affect various organs and is characterized by different clinical phenotypes. While the treatment of renal involvement is quite standardized, the therapeutic approach to extra-renal manifestations is subjected to a degree of variability.Objectives1. To describe extra-renal disease flares in terms of clinical phenotype and outcomes in SLE patients 2. To compare data from a real-life setting with a machine learning (ML) approach.MethodsThis study is a retrospective analysis of data from a monocentric cohort of SLE patients who experienced a disease flare between 2015 and 2020. Each flare was followed for one year and was classified according to the organ involvement and categorized according to the BILAG definition of flare. At baseline and at 3,6,12 months the following variables were collected: disease activity (SELENA-SLEDAI score), ongoing therapy and disease state (DORIA definition of remission). Demographic data and previous organ involvement were retrieved from clinical charts. Flares’ features at baseline and during follow up were analyzed in terms of explained variance across the dataset’s Principal Components and clustered with a hierarchical unsupervised learning approach. A ML model based on neural networks was built to early detect flares’ therapeutic difficulty: it was validated after data augmentation to satisfy statistical requirements during the training phase.Results66 extra-renal flares were investigated (Table 1); 5 flares (7.5%) were treated with glucocorticoid (GC) pulses and 61 (92.5%) with oral GC therapy, while an immunosuppressive (IS) treatment was prescribed in 44 flares (66.7%). The remission rate at 12 months for the whole group was 50%, with musculo-skeletal (MS) flares, mucocutaneous (MC) flares and others (neuropsychiatric, cardiopulmonary, constitutional, haematologic) that was respectively 63.6%, 31.3% and 41.2%, showing lower rate of remission for MC flares. In 12 months, 17 flares (25.8%) did not respond to treatment (non-responders), requiring an increase in the dose of GC or the introduction of a new IS therapy. Using a machine learning approach, we were able to identify 4 flare clusters, grouping flares in relation to phenotypic characteristics (Figure 1), and recognized statistically relevant features for patients’ stratification (cluster 1“flare in systemic disease with high activity”, cluster 2 “outcast flares”, cluster 3 “flare in polymorphic disease with mild activity” and cluster 4 “recurrent skin flares”). Interestingly, cluster 4 (recurrent skin flares) was associated with the lowest rate of remission at 12 months with respect to clusters 1, 2, and 3 (33% vs 40%, 76.5% and 56% respectively). Moreover the neural network model correctly predicts difficult to treat flares in up to 80% of the casesTable 1.WHOLE GROUPMUSKELMUCOCUTCONSTITUTIONALCARDIOPULMHAEMATOLNEUROpNUMBER (%)6633 (50)16 (24.2)7 (10.6)4 (6.1)5 (7.6)1 (1.5)SLEDAI at baseline median (IQR)7 (4-29)8 (6-10)5.5 (4-10)5 (4-9)9 (4.5-12)5 (5-6)29 (29-29)SLEDAI 12 mos median (IQR)2 (0-20)0.5 (0-4)3 (0-4)3 (2 – 4)0 (0-0)2 (0-3)14 (14 – 14)REMISSION 12 mos number (%)33 (50)21 (63.6)5 (31.3)4 (57.1)2 (40)2 (40%)1 (100)0.217NON RESPONSE 12 mos number (%)17 (25.8)8 (25)5 (31.3)2 (28.6)1 (20)1 (20%)1 (100)0.467Figure 1.Flare clusters.ConclusionThese data suggest that, in a real-life setting, the clinical response rate to therapy of patients with an extra-renal flare is not satisfactory, thus identifying an unmet need in the treatment of SLE and highlighting the absence of a standard treatment. Both the real-life data and the machine learning approach identify flares with MC manifestations as the most difficult to treat with the lower rate of remission after one year. Further prospective studies are necessary to improve the neural network model; ML techniques could help in the early identification of difficult to treat flares to be candidates for new and more aggressive therapeutic strategies for extra-renal manifestations.Disclosure of InterestsNone declared

BackgroundFatigue in SLE has a multifactorial origin and disease activity seems to contribute only minimally to its genesis. Therefore, non-pharmacological therapeutic strategies should also be considered in the management of fatigue. There is some evidence on the effectiveness of aerobic exercise programs in improving fatigue, without a negative impact on disease manifestations.Objectivesthe aim of this study was to analyze fatigue and Health Related Quality of Life (HRQoL) in a monocentric cohort of patients with SLE, in a condition of stable remission or low disease activity, before and after a program of physical exercise, through the administration of validated Patient Reported Outcomes (PROs).Methodsthis is a cross-sectional interventional study which included patients with SLE, aged between 18 and 55 years, in a condition of stable (≥12 months) remission (DORIS)1 or low disease activity (LLDAS)2. Patients enrolled had a FACIT score ≤40 in the previous 6 months. Patients with other possible causes of fatigue (e.g.: anemia, hypothyroidism, severe vitamin D deficiency), active arthritis or physical disabilities were excluded. For each patient, demographics, comorbidities, treatment, clinical and laboratory data were collected. Disease activity was evaluated with the SELENA-SLEDAI and organ damage with the SLICC/DI. Each patient completed the following PROs before and after the interventional program: SF-36, FACIT-Fatigue, LIT, HADS. Due to the limitations related to the COVID-19 pandemic, the physical exercise sessions were carried out using the Google Meet digital platform. Patients were asked to participate to at least 70% of the lessons. The physical exercise program included moderate intensity aerobic exercises (muscle strengthening, joint mobility, breathing, static and dynamic stretching, balance and neuro-dynamics); workouts were performed 3 times a week, consisting of 60 minutes each. The program lasted for 12 weeks.Resultswe enrolled 12 female patients, regularly followed at the Rheumatology Unit of Pisa; only 9 of them completed the study (mean age 38.56 ± 9.1 years; median disease duration 7 years (IQR 5,25-9,75)). 8/9 were in stable remission, while 1/9 was in LLDAS for the presence of leukopenia.2/9 patients presented organ damage, one for cataract and one for renal insufficiency, while none presented damage in the musculoskeletal system. 33.3% of patients had fibromyalgia. 88.8% was on treatment with Hydroxychloroquine, 55.5% was on low dose steroids (2±1.9 mg/daily), 33.3% was on Mycophenolate Mofetil; only 1 patient was on Belimumab. All PROs showed a trend to improvement at the end of the 12-week program of physical activity (Table 1). We demonstrated a statistically significant improvement of: FACIT, LIT, depression score of the HADS and MCS of the SF-36. The items of role physical (RP), vitality (VT) and mental health (MH) of the SF-36 also showed a significant improvement.Table 1.Scores of PROs before and after the physical exercise program.PROsMean scores at baselineMean scores after the 12-week exercise programpFACIT30.2 ± 4.939.3 ± 7.20.01PF73.18 ± 10.978.9 ± 10.50.18RP50 ± 13.267.4 ± 18.60.03BP52 ± 12.154.1 ± 11.10.73GH41.7 ± 11.148.4 ± 11.10.07VT34.7 ± 12.559.0 ± 14.20.002SF58.3 ± 15.666.7 ± 16.70.3RE55.5 ± 21.569.4 ± 18.00.13MH58.3 ± 15.867.2 ± 16.20.03PCS43.8 ± 4.046.1 ± 4.80.19MCS38.6 ± 8.845.6 ± 8.70.03LIT36.9 ± 14.227.5 ± 14.10.05HADS (A)9 ± 4.47.7 ± 3.20.4HADS (D)7.9 ± 4.45.1 ± 2.960.05ConclusionIn a small cohort of SLE patients in remission but with severe fatigue, in the difficult context of COVID-19 pandemic, we demonstrated that an online program of physical exercise may determine a significant improvement of fatigue, perception of disease burden and mental health. In the context of a multidisciplinary management, finding effective intervention programs to improve fatigue and HRQoL in SLE patients appears of utmost importance, with the final aim of improving patients’ health status.References[1]PMID 27884822; 2PMID 26458737Disclosure of InterestsNone declared

BackgroundA growing interest has been addressed to the study of lung involvement in systemic autoimmune diseases. Non-serositic pulmonary manifestations have also been described in SLE. However, little is known about their exact prevalence, clinical features and outcomes.ObjectivesTo describe the prevalence, clinical and immunological characteristics of symptomatic non-serositic lung involvement in a monocentric cohort of SLE patients.MethodsThis observational, retrospective study included patients with SLE, regularly followed at the Rheumatology Unit of Pisa, that presented a clinically relevant non-serositic pulmonary involvement during their disease history. Patients with lung manifestations related to other causes (e.g. infections, emphysema, Chronic Obstructive Lung Disease, bronchial asthma etc.) were excluded. The following data were collected from clinical charts: demographics, smoke exposure, comorbidities, respiratory symptoms, disease duration and disease activity (SELENA-SLEDAI) at the onset of lung involvement, immunological profile, treatment, CT and spirometry parameters.ResultsOver 450 SLE patients in regular follow-up, we found 11 female patients with a history of clinically relevant non-serositic lung involvement: 7 interstitial lung disease (ILD), 2 acute lupic pneumonitis (ALP), 1 diffuse alveolar hemorrhage (DAH) and 1 shrinking lung syndrome. 45.4% of patients had a history of smoke exposure and had stopped smoking on average 9 years before the onset of lung manifestations. For the 2 patients with ALP, this was the first manifestation of SLE. Among the other 9 patients, lung involvement was diagnosed after a mean disease duration of 14 ± 15 years. At the diagnosis of pulmonary involvement, 10/11 patients presented respiratory symptoms and an overall active disease, with a median SLEDAI of 9 (IQR 6-13). Clinical characteristics are summarized in Table 1. All patients were hospitalized and 2 of them (1 ALP and 1 DAH) were admitted in intensive care unit.Table 1.Clinical characteristics at the diagnosis of lung involvementSystemicActive skin manifestations36%Arthritis36%Fever36%Leukopenia36%Hypocomplementemia91%Anti-dsDNA positivity36%RespiratoryDyspnea54%Exertional dyspnea18%Cough45%Acute respiratory failure27%As for the immunologic profile, SSA/Ro60 were positive in 72% of patients and SSA/Ro52, SSB, U1-RNP in 36%; 36% had Sjogren Syndrome (SS) in overlap.Spirometry was available for 6/11 patients: a restrictive pattern and a moderate/severe reduction of diffusing capacity of the lung for carbon monoxide was found in 5 patients.In the ILD subgroup, the most prevalent CT pattern was the Non-specific interstitial pneumonia (NSIP) (5/7). 2 patients presented a Bronchiolitis obliterans/organizing pneumonia (BOOP) pattern.Lung involvement was the driving manifestation in the treatment choice for 6/11 patients: 1 DAH, 2 ALP, 1 Shrinking lung and 2 ILD. All received pulse steroids and in 3 cases (2 ILD and 1 DAH) cyclophosphamide was added for the induction treatment; the patient with Shrinking lung had an overlap SS and was treated with Rituximab.At last visit (mean follow-up of 8 ± 8.7 years since lung disease onset), 7/11 patients presented no respiratory symptoms and a complete resolution of CT alterations. 3/11 presented a residual exertional dyspnea and mild spirometry alterations. No patients developed respiratory insufficiency; only 1 patient died for cardiovascular complications.ConclusionIn our large cohort of SLE patients, non-serositic lung involvement seems to be overall rare; the most frequent type of lung manifestation is ILD which appears to be associated with anti-SSA/SSB and anti-U1RNP positivity. The low prevalence of lung involvement (2.4%) in our cohort could be due to the presence of patients with a subclinical involvement. Further studies are needed to assess the real prevalence of subclinical lung manifestations in SLE and to identify the clinical phenotype of patients more prone to develop pulmonary disease.Disclosure of InterestsDavide Schilirò: None declared, Elena Elefante: None declared, Chiara Stagnaro: None declared, Viola Signorini: None declared, Dina Zucchi: None declared, Francesca Trentin: None declared, Gaetano La Rocca: None declared, Linda Carli: None declared, Francesco Ferro: None declared, Chiara Tani: None declared, Marta Mosca Speakers bureau: advisor LILLY, ASTRA ZENECA, GSK, Consultant of: advisor LILLY, ASTRA ZENECA, GSK

BackgroundPatients with systemic autoimmune diseases (SADs) are often treated with drugs that interfere with the immune system and previous data showed a reduced seroconversion rate after anti-SARS-CoV2 vaccine in these subjects compared to healthy controls1. Administration of a booster dose of the vaccine could be particularly important in these patients, but data available to date are still scarce.ObjectivesTo evaluate the antibody response to the booster dose of mRNA SARS-CoV2 vaccine in patients with SADs and to compare it to the response after completion of the first vaccination course. Secondly, to find possible correlations between a low antibody titre and patients’ clinical features, with special regard to ongoing immunosuppressive therapies.MethodsConsecutive patients with an established diagnosis of SADs undergoing SARS-CoV2 vaccine were prospectively enrolled from January 2021; among them, we selected the patients who received the third vaccination dose between September and December 2021. Demographic and clinical data were collected at enrolment (sex, age, diagnosis, disease duration, ongoing therapies, previous SARS-CoV2 infection, presence of hypogammaglobulinemia); the last three elements were reassessed at each follow-up visit. Blood samples were collected 4 weeks both after the second (W4a) and the third (W4b) dose of the vaccine; a minority of patients was also tested 12 weeks after the second dose (W12). IgG antibodies to SARS-CoV2 receptor-binding domain (RBD) and neutralizing antibodies inhibiting the interaction between RBD and angiotensin converting enzyme 2 were evaluated. IgG anti-RBD were detected by solid phase assay on plates coated with recombinant RBD, while neutralising antibodies by using the kit SPIA (Spike Protein Inhibition Assay). Cut-off values were defined as the 97.5th percentile of a pre-vaccine healthy population. Statistical analysis was performed using IBM SPSS Statistics 20 and GraphPad Prism statistical packages. P values ResultsForty-five patients (95.6% female; mean age ±SD 55.6±14.1 years; mean disease duration 12.9±10.6 years) were enrolled. Diagnosis was in most cases connective tissue disease (31/45, 68.9%), followed by inflammatory arthritis (11/45, 24.4%) and systemic vasculitis (3/45, 6.7%). Two patients (4.4%) had a previous SARS-CoV2 infection and three had hypogammaglobulinemia (6.7%). At the time of the second dose, 18/45 patients were treated with glucocorticoids (GCs) [mean daily 6-methylprednisolone (6MP) dose 3.9 mg (min. 2, max. 14)], 17/45 with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 12/45 with biologic DMARDs (bDMARDs). At the third dose administration, 19/45 patients were treated with GCs [mean daily 6MP dose 4.1 mg (min. 1.5, max. 10)], 18/45 with csDMARDs and 13/45 with bDMARDs. Anti-RBD IgG were positive in 42/45 patients (93.3%) at W4a, in 16/18 (88.9%) at W12 and in 42/45 (93.3%) at W4b. Neutralizing antibodies were present in 38/45 patients (84.4%) at W4a, in 14/18 (77.8%) at W12 and in 42/45 (93.3%) at W4b. Both anti-RBD IgG titers and neutralizing antibody titers significantly increased after the third dose if compared to W4a (pConclusionOur data suggest that in patients with SADs there is a decline in the antibody titers developed after COVID-19 vaccination, however the booster dose is effective in restoring an adequate antibody titre. These data consolidate the importance of a booster dose of COVID-19 vaccination in patients with SADs to aid in the generation of an immune response.References[1]Jena A et al. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: systematic review and meta-analysis. Autoimmun Rev. 2022AcknowledgementsThe authors would like to thank all the patients who participated in the study and the nurses Sabrina Gori, Rosanna Lo Coco, Lucia Pedrocco, Carla Puccini, Pasqualina Semeraro, Manuela Terachi, Maria Tristano, Valentina Venturini and Catiuscia Zoina who took care of the patients.Disclosure of InterestsNone declared

BackgroundLow medication adherence is a well known issue in the management of patients with systemic autoimmune diseases (SAD), little however is known on adherence to medication during pregnancy, especially in these patients with high risk pregnancies.ObjectivesThis study is aimed at evaluating the level of adherence to medication in pregnant patients with SAD in comparison with non-pregnant patients with SAD, and at identifying determinants of low adherence.MethodsPregnant and non-pregnant patients with an established diagnosis of SAD were consecutively enrolled. Pregnant patients were included in a tight monitoring protocol for high risk pregnancies, and treatments were checked every month. The following data were collected at enrolment: epidemiological and demographic characteristics, disease duration and type of medications. Each patient completed the following anonymous questionnaires: the 8-item Morisky Medication Adherence Scale (MMAS-8) and Hospital Anxiety and Depression Scale (HADS) to assess the presence of anxiety and depression. With regard to MMAS-8, we assessed adherence to hydroxychloroquine (HCQ) and to other disease modifying antirheumatic drugs (DMARDs) separately. We considered a score ≥ 6 as indicator of good adherence. Vitamins and dietary supplements were not considered.ResultsA total of 80 pregnant women and 72 non-pregnant women were enrolled. Clinical data and results of the questionnaires are summarized in Table 1.Table 1.Characteristics of the cohortPregnant patients N=80Non-pregnant patients N=72P valueAge at study entry (years, mean ±SD)35.8±4.340.1±12.20.001Disease duration (years, mean ±SD)8.5±6.68.6±9.1n.sNumber of tablets/day (mean ±SD)4.3±1.64.1±1.8n.sNumber of assumption/day (mean ±SD)1.4±0.61.6±0.8n.sScore MMAS for HCQ (mean ±SD)6.99±0.26.38±0.20.039Score MMAS for other DMARDs (mean ±SD)6.99±0.36.39±0.20.018Patients with good adherence to HCQ (%)38/50 (76.0%)34/59 (57.6%)0.044Patients with good adherence to medications (%)53/71 (74.6%)37/60 (61.7%)n.sPatients with low adherence to HCQ (%)12/50 (24%)25/59 (42.4%)0.044Patients with low adherence to medications (%)18/71 (25.4%)23/60 (38.3%)n.sAnxiety (%)20 (25%)30 (41.7%)0.029Depression (%)11 (13.7%)19 (26.4%)0.051MMAS-8 score was significantly higher in pregnant women both for HCQ (p=0.039) and other DMARDs (p=0.018), as well as the rate of patients with good medication adherence for HCQ (76.0% vs 57.6%, p=0.044). The rate of patients with good medication adherence for other DMARDs was higher in pregnant patients (74.6% vs 61.7%) but this different was not statistically different.Demographic and clinical characteristics and the number of therapies received didn’t seem to influence treatment adherence. Fifty patients (32.8%) suffered from anxiety, and this disorder was a significant determinant of low medication adherence in all groups. Conversely, depression didn’t seem to have an impact on adherence on neither group.ConclusionOverall, pregnant patients with SAD had a good adherence to prescribed medication; nevertheless, 25% of patients didn’t take therapies adequately despite being closely monitored in a dedicated clinic for high risk pregnancies and an adequate pregnancy counselling; anxiety seems to be one determinant of low medications adherence both in pregnant and non-pregnant women.Disclosure of InterestsNone declared

BackgroundGlucocorticoids (GC) are a cornerstone for the treatment of Systemic Lupus Erythematosus (SLE) manifestations but there is still open debate concerning their optimal therapeutic employment.ObjectivesTo describe and compare the GC therapeutic strategies used in a real-life setting for the initial treatment of SLE flares.MethodsThis study is a retrospective analysis of data from a monocentric cohort of SLE patients who registered a disease flare between 2015 and 2020. Flares were first categorized in “pulse-treated” (PT) and “non pulse-treated” (NPT). PT flares were then divided into “low-dose regimen” (250 mg iv 6MP for 3 consecutive days or less) and “high-dose regimen” (more than 250 mg iv 6MP for 3 days). GC daily and cumulative 6MP doses, rate of remission and relapse were evaluated at 3, 6 and 12 months.Results101 flares were analyzed (30 PT and 71 NPT). PT flares were more severe in terms of median SLEDAI (PT 16(12-22) vs NPT 8(5-10) p=0,00) and BILAG score index (BILAG A PT 71% vs NPT 30% p=0,001). PT patients received significantly higher GC doses at 1 month (PT median cumulative dose 1372 IQR 1028 – 3076 mg of 6MP vs NPT median 160 IQR 120-288 mg of 6MP, p=0,000), 6 months (PT median cumulative dose 2964 IQR 2294 – 4305 mg of 6MP vs NPT 880 IQR 720 – 1284 mg of 6MP, p=0,000) and 12 months (PT median cumulative dose 3510 IQR 3014-5025 vs NPT median cumulative dose 1571 IQR 1098 – 2122 mg of 6MP, p=0,000). Characteristics of flares that were treated with low-dose (N=19) or high-dose (N=11) pulse regimen are summarized in Table 1. As expected, the “low-dose regimen” subgroup received lower cumulative GC dosage over time. However, no statistically significant differences were found neither in term of disease severity at baseline nor in term of disease activity, remission rates or new flares over time.Table 1.Comparison between low-dose pulse regimen and high-dose pulse regimen in terms of cumulative GC dose and outcome in the first year after a SLE flareMedian GC doses (6MP)Low-dose regimenN=19 (63,33%)High-dose regimenN=11 (36,67%)P value Median SLEDAI16 (12 -20)18 (8-24)0,6186BILAG score (A, B, C)A=14, B=4, C=1A=10, B=1, C=00,488Cum. dose 1 mo1350 (1028 – 1534)1752 (960 – 2356)0,126Cum. dose 3 mos1858 (1604 – 2463)2784 (2184 – 3240)0,040Cum. dose 6 mos2450 (2218 – 3586)3456 (2906 – 4380)0,029Cumulative doses 12 mos3150 (2851 - 4448)4246 (3591 – 5772)0,011Remission 3 mos no – (%)2 (10%)0 (0%)0,265Remission 6 mos no – (%)8 (42%)1 (9%)0,057Remission 12 mos no – (%)12 (63%)5 (45%)0,346Median SLEDAI 3 mos4 (2 – 9)9 (4 – 12)0,138Median SLEDAI 6 mos3 (0 - 4)4 (0 – 9)0,154Median SLEDAI 12 mos2 (0 – 5)2 (0 – 12)0,363New flares 6 mos no – (%)2 (10%)1 (9%)0,900New flares 12 mos no – (%)2 (10%)2 (18%)0,552GC=glucocorticoids, 6MP=6-methylprednisolone, no=number, Cum.=cumulative, mos=monthsConclusionThese data suggest that in a real-life setting, pulse GC therapy is preferred over oral administration for severe SLE flares and entails administration of high cumulative doses of GC. However, the experience outlined suggests that the low-dose pulse regimen is as effective in remission induction of severe flares as the high-dose regimen, allowing significant GC sparing. Since the cumulative GC dose is a known strong predictor of organ damage, strategies aimed to minimize the GC dosage should be encouraged.Disclosure of InterestsNone declared

BackgroundSince the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefits of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group).ObjectivesTo evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://brightoncollaboration.us/wp-content/uploads/2021/01/SO2_D2.1.2_V1.2_COVID-19_AESI-update-23Dec2020-review_final.pdf)MethodsThe first ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defined as at least one of the following: new manifestations attributable to disease activity, hospitalization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants.ResultsA cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren’s syndrome (SS,12%), idiopathic inflammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Danlos’s syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the first and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%).ConclusionThis preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the first month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.Table 1.AEs and disease exacerbations per diseaseDiagnosisPatients enrolled (%) (n=300)EAs after 1st and 2nd dose (%)Exacerbations (%)APS25714EDS45033IIM10527MCTD44225SS12598SLE44698SSC16492UCTD850-AcknowledgementsVACCINATE is a study promoted by the European Reference Network on rare and complex connective tissue diseases, ERN ReCONNET. This publication was funded by the European Union’s Health Programme (2014-2020)Disclosure of InterestsNone declared

BackgroundThe optimization of HRQoL in SLE patients is defined as one of the treatment goals in the 2019 EULAR recommendations1 for the management of SLE. Most studies have examined HRQoL at one point in time, while the few longitudinal studies do not report a clear variation in Patient Reported Outcomes (PROs) with respect to changes in disease activity. It would be important to understand if, even in a real-life setting, the improvement of patients’ HRQoL may represent an achievable target.Objectivesthe aim of this study was to analyze HRQoL over time in a monocentric cohort of patients with SLE and investigate which disease-related factors determine short-term variation of HRQoL in a real-life setting.Methodsthis is a longitudinal, prospective monocentric study which included consecutive adult outpatients with SLE (1997 ACR classification criteria), regularly followed at the Rheumatology Unit of Pisa. Patients were enrolled over a period of 2 years, before the pandemic outbreak, and had at least 2 assessments per year. For each patient, demographics, comorbidities, treatment, clinical and laboratory data were collected. Disease activity was evaluated with the SELENA-SLEDAI and organ damage with the SLICC/DI. We defined as a significant variation of disease activity, a difference of clinical SELENA-SLEDAI ≥ 4 points between 2 subsequent evaluations. At each visit, patients completed the following PROs: SF-36, FACIT-Fatigue and LIT.Resultswe enrolled 210 consecutive SLE patients, mainly female (93.8%) and of Caucasian ethnicity (97.1%), with a mean age at enrollment of 45.1±12.7 years and a median disease duration of 13 years (IQR 5-21). At baseline, the median SLEDAI of the cohort was 2 (IQR 0-4). The most frequent active disease manifestations were: articular (17.1%) and hematological (15.2%); 6.7% of patients had active renal disease. 47.14% had a SLICC-DI > 0 with a median SLICC-DI among them of 2 (IQR 1-3). 11.43% of patients had a concomitant fibromyalgia. Most patients were on Hydroxychloroquine (78.1%) and low dose glucocorticoid (55.2%), with a median daily dose of 2 mg (IQR 0-4) of prednisone equivalent; 41.4% were on conventional immunosuppressants and 11.9% on biologics, mainly belimumab. The median scores of PROs at enrollment are reported in Table 1. At baseline, fibromyalgia confirmed to have a significant negative impact on all PROs after adjustment for confounding factors (pppTable 1.PROs scores at baseline.PROsMedian scores at baselineSF-36 PCS58 (IQR 49.09- 68)SF-36 MCS57 (IQR 46.42-67)FACIT42 (IQR 32-46)LIT20 (IQR 7.5-40)Conclusionour findings seem to suggest that HRQoL over time in outpatients with longstanding SLE tends to be stable (maybe because patients are able to adapt to their illness) or varies unpredictably, maybe influenced by not disease-related factors. Further studies are needed to better understand which factors influence HRQoL over time and which questionnaires are more sensitive to catch its variation.References[1]PMID: 30926722Disclosure of InterestsNone declared

Suberin metabolism plays a crucial role in the compartmentalization of the necrotic bark tissues in cypress clones resistant to bark canker caused by Seiridium cardinale. In cypress, the main mechanism of resistance to the bark canker caused by the fungal pathogen Seiridium cardinale involves the post-infectional development of a well-structured necrophylactic periderm (NP). The impermeability and effectiveness of NP against pathogens has been associated with cell wall suberization. In canker-resistant and susceptible C. sempervirens clones, the transcript accumulation of four genes involved in suberin biosynthesis (Acyl-CoA thioesterase, stearoyl-ACP-desaturase, Caffeoyl-CoA-3-O-methyltransferase 1 and Peroxidase 21) was studied in inoculated and wounded bark tissues through qPCR assay during a 3 month trial. Quantification of non-structural carbohydrates in the same targeted tissues was also performed by HPLC. In the canker-resistant clone, transcript accumulation of all four examined genes significantly increased after both inoculation or wounding more than in the susceptible clone, and the maximum difference between the two clones was observed after 30 days. The type of clone significantly affected the transcript accumulation of all the four examined genes (main effects ANOVA). The total soluble sugars content detected in the bark tissues was constitutively similar in both clones, and only slight differences in the carbon balance were detected between the two clones 90 days after inoculation or wounding. Histological observations of bark sections stained with Sudan red 90 days after inoculation, showed that in the canker-resistant clone a greater suberin deposition occurred in the NP, which resulted thicker and better structured when compared to the susceptible clone.

The ability to produce indole-3-acetic acid (IAA) through the indole-3-acetamide (IAM) pathway as well as cytokinins is a common trait of Pseudomonas savastanoi populations causing disease on oleander and olive. These phytohormones are required for the induction and development of an outgrowth of plant cell tissue termed a knot. However, in myrtle orchards of Sardinia (Italy), strains of P. savastanoi unable to produce cytokinins were found coexisting with cytokinin-producing strains. Data presented here show that the ability to produce IAA through the IAM pathway is also a variable trait within this population, raising questions on the exact role of these plant growth substances in the disease process on myrtle. Three P. savastanoi strains were selected based on their differential ability to produce phytohormones in vitro, and their interaction with the host was investigated over a period of 8 months using histological methods. All strains successfully invaded the infected twigs, moving systemically (unhalted by host defences) upward and downward from the inoculation point, both by completely degrading the cell walls and by taking advantage of the xylem vessels and intercellular spaces. Moreover, all strains induced the development of cankers, which slowly evolved into typical knots only on the twigs inoculated with the phytohormone-producing strains. This study further demonstrates that cytokinins and IAA are essential for knot development; moreover, it ascertains that bacterial production of cytokinins is not necessary for host colonization and for the expression of pathogenicity (i.e. the ability to cause disease) of P. savastanoi on myrtle.

Bridge load limit monitoring is a major problem in the Philippines. Since this was not implemented strictly, the structural integrity of the bridges was affected hence it resulted to frequent maintenance, retrofitting of strucutral members and collapse. The integrity of the bridge continously decreases through time once the maximum load limit was experienced by the structure. Therefore, this study aims to emphasize the importance of traffic load monitoring in conducting structural health assessment of bridges aside from earthquake and mass loads. The 7.7% increase in the flexure stress of the bridge deck indicates that truck loading has a significant effect on the bridge. In addition for this, variation on the truck volume for peak hours and non peak hours will correlate to the reading of the smart sensor attached on the bridge for structural health monitoring.

Background Rheumatic Diseases (RD) frequently affect women during reproductive age, therefore counselling on family planning is crucial for their quality of life. Children’s outcome is a major topic, but no large studies are available. Objectives To assess the long-term health conditions of children born to women with RD in a large multicentre cohort. Methods 24 Rheumatology Centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to consecutive patients (18–55 years) in September 2015. Data were analysed dividing children upon maternal diagnosis: Chronic Arthritides (CA) and Connective Tissue Diseases (CTD). Results Data were collected for 320 children (166 males, 52%) born to 184 mothers (63 CA and 121 CTD). At the time of interview, children had a mean age of 17.1±9.6 years. Preterm delivery ( Conclusions In this long-term follow-up of children born to mothers with RD in this large, multicenter study of randomly interviewed women each AIID did not display a significantly increased frequency as compared to the literature; only coeliac showed a mild increased frequency. Children with LD had a tendency to cluster in the group of mothers with CTD, especially after maternal diagnosis (4/63, 6.3%), with a higher frequency as compared to general paediatric population. No significant relationships between ND/LD and prematurity, intrauterine drug exposure or maternal autoantibodies were identified. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma. The authors wish to thank Patients Associations and Participants to the survey. Disclosure of Interest None declared

Background Rheumatic diseases (RD) predominantly affect young women during reproductive age. Pregnancy, contraception and family planning (FP) are crucial for the quality of life of these patients. Objectives We aimed to investigate 9women9s health9 through a self-reported questionnaire. Answers from patients with connective tissue diseases (CTD) vs chronic arthritis (CA) were compared. Methods 24 centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to women with RD (18–45years) regularly attending their outpatient clinics. Results Answers were collected from 249 CTD vs 149 CA patients. Their desire to have children was influenced by RD in 40% of cases: half of them reduced the number of children they wanted (Table 1). 39% CA vs 29% CTD were afraid of being mother because of disability. 24% CTD vs. 18% CA had at least one miscarriage; 21% CTD vs. 2% CA had more than one. 31% CTD and 34% CA were never asked about their desire to have children. 61% CTD vs 70% CA received counselling about contraception, given by a gynaecologist (G) (58% vs 64%), rheumatologist (R) (22% vs 14%) or both (7% vs 9%). 60% in both groups received a counselling before pregnancy: 34% vs 39% from R and G, 14% vs 22% by R. This positively changed family planning in 64% vs 59%. We created a Knowledge Index (based on the average of the normalized performed scores on 6 key questions for different sections): 55% CTD patients vs 44% CA had a medium-high score. A higher score directly correlated with the desire to became pregnant and with a multidisciplinary counselling. Conclusions This survey suggested that CTD have a major impact on FP and family size, possibly mediated by the increased rate of miscarriages as compared to CA. Concerns about reproductive issues could be positively overcome by adequate counselling. Rheumatologists should implement the discussion about FP and the compatibility of drugs with pregnancy in the management of young women with RD, especially those with CTD for whom contraception and pregnancy have particular implications. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients9 Associations and Participants Disclosure of Interest None declared

Background Rheumatic diseases (RD) affect women during reproductive age. Children9s outcome is a major topic for counselling on family planning, but no large studies are available. Objectives We aimed at assessing the long-term health conditions of children born to mothers with RD through a self-reported questionnaire. Methods 24 Rheumatology Centers distributed the questionnaire (65 multiple choice and 12 open-answer questions) to consecutive women with RD attending their outpatient clinic during September 2015. Data were compared according to maternal diagnosis (MD) -chronic arthritis (CA) or connective tissue disease (CTD)- and to the timing of pregnancy (before or after MD of RD). Results The survey yielded data about 269 children born to 184 mothers (63 CA, 121 CTD). According to MD, children had a mean age of 17.1 (±9.6 SD) and 14.4 (±9.0 SD) years at the time of interview, and male children were 52/93 (56%) and 91/176 (52%), respectively. Twenty-nine children in the CA group (31.2%) and 64 in the CTDs group (36.4%) were born after MD of RD. Pre-term delivery (before 37 weeks) was observed in 48 cases (17.8%), mostly children born to mothers with CTD (37/48, 77%). Regarding school performance, 12 children (4.5%) repeated one year of school, in 7 cases for indolence, in 3 for learning disabilities (LD)/health problems (HP), in 2 for family problems. Eleven of these children were born before MD. Overall, 9 children (3.3%) were diagnosed with a LD and 53 children were affected by HP requiring either hospitalization or evaluation by a Specialist (Table). Three children (1%) were affected by autoimmune disease. Conclusions The long-term follow-up of children born to women with RD is reassuring of an outcome similar to that of the general pediatric population (GPP). Autoimmune diseases are not frequent. Problems seem to cluster in children born to CTD, especially after MD, with a higher frequency of LD (6.3% vs 2.5–3.5% of GPP), but no particular pattern of exposure to maternal autoantibodies nor drugs was observed. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients Associations and Participants to the survey Disclosure of Interest None declared

In recent years, with the increasing social awareness of safety in medical practice, improving clinical skills has become very important, especially for recently graduated dentists. Traditionally, mannequins have been used for clinical skill training, but a mannequin is quite different from a real patient because they have no autonomous movement or conversational ability. This indicates that pre-clinical simulation education is inadequate. We have, therefore, developed a robot patient that can reproduce an authentic clinical situation for dental clinical training. The robot patient, designed as a full-body model with a height of 157 cm, has eight degrees of freedom in the head and the ability to perform various autonomous movements. Moreover, saliva secretion and conversation with the trainee can be reproduced. We have introduced the robot patient into an objective structured clinical examination targeted at fifth-grade students in our dental school to evaluate their skills in cavity preparation, whilst considering the safety of the treatment. As a result, many of the students were able to deal appropriately with a patient's unexpected movement. Moreover, results of a questionnaire survey showed that almost all the students recognised the educational value of the robot patient especially for 'risk management', and they preferred the robot patient to traditional mannequins. Practical application of the robot patient in dental clinical education was evaluated through the experiences of the fifth-grade students, which showed the effectiveness of the robot patient in the dental field.

This review summarises most currently used indices to assess and monitor patients with systemic lupus erythematosus (SLE) in clinical trials, long-term observational studies, and clinical care. Six SLE disease activity indices include the British Isles Lupus Assessment Group Index (BILAG), European Consensus Lupus Activity Measurement (ECLAM), Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Lupus Activity Index (LAI), and Systemic Lupus Erythematosus Activity Questionnaire (SLAQ). Three SLE responder indices include Responder Index for Lupus Erythematosus (RIFLE), SLE Responder Index (SRI), and BILAG Based Combined Lupus Assessment (BICLA). Three SLE damage indices include the Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACE-DI), Lupus Damage Index Questionnaire (LDIQ), and Brief Index of Lupus Damage (BILD). The SLAQ, LDIQ and the BILD are patient self-report questionnaires, which appear to give similar information to physician-completed indices, but are pragmatically more easily completed as patients do almost all the work. Additional self-report indices which have been used to assess and monitor patients with in SLE include a generic general health short form 36 (SF36), a SLE-specific Lupus Patient Reported Outcome (LupusPRO), and a generic rheumatology index, Routine Assessment of Patient Index Data 3 (RAPID3). These activity, response, damage and patient self-report indices have been validated at different levels with no consensus about what it is the most appropriate for every setting. Sensitive and feasible assessment of SLE in clinical trials, observational studies, and busy clinical settings remains a challenge to the rheumatology community.

In recent years, with the increasing social awareness of safety in medical practice, improving clinical skills has become very important, especially for recently graduated dentists. Traditionally, mannequins have been used for clinical skill training, but a mannequin is quite different from a real patient because they have no autonomous movement or conversational ability. This indicates that pre-clinical simulation education is inadequate. We have, therefore, developed a robot patient that can reproduce an authentic clinical situation for dental clinical training. The robot patient, designed as a full-body model with a height of 157 cm, has eight degrees of freedom in the head and the ability to perform various autonomous movements. Moreover, saliva secretion and conversation with the trainee can be reproduced. We have introduced the robot patient into an objective structured clinical examination targeted at fifth-grade students in our dental school to evaluate their skills in cavity preparation, whilst considering the safety of the treatment. As a result, many of the students were able to deal appropriately with a patient's unexpected movement. Moreover, results of a questionnaire survey showed that almost all the students recognised the educational value of the robot patient especially for 'risk management', and they preferred the robot patient to traditional mannequins. Practical application of the robot patient in dental clinical education was evaluated through the experiences of the fifth-grade students, which showed the effectiveness of the robot patient in the dental field.

症例は51歳の女性,肛門出血を主訴に来院した.直腸指診および大腸内視鏡検査で肛門管の4時方向に易出血性のポリープ様病変を認めた.生検組織診断で低分化扁平上皮癌と診断され,経肛門的に局所切除術を施行した.組織学的には深達度はm(粘膜内癌),乳頭状,樹枝状に増殖する低分化の扁平上皮癌でbasaloid cellを主体としていた.肛門管の粘膜内癌の報告は少なく,発育形態が特徴的で病理学的に興味ある症例であるので報告する.

Glucocorticoids (GCs) remain the cornerstone of the treatment of systemic lupus erythematosus (SLE), despite advances in immunosuppressive drugs, therapeutic protocols and development of new drugs. GCs rapidly control disease activity in mild as well as in severe disease, although these effects might not be maintained over time. The majority of SLE patients have received GC treatment; in some cohorts up to 80% of patients continue this treatment indefinitely as 'maintenance' therapy, at low doses of less than 7.5 mg/day. The positive effects of GCs are diminished by adverse effects, particularly at high doses. The cumulative dose of GCs clearly is related to adverse effects. Several unresolved issues in GC treatment of SLE include the optimal doses to be used in induction and maintenance, and in particular how high the dose for how long. It remains unclear whether GCs should be continued indefinitely and, if not, when and how this treatment should be discontinued. Both clinical trials and observational data will help to clarify these issues.

A ferroelectric liquid crystal (FLC) shutter array with an a-Si:H thin-film transistor (TFT) drive, designed for a low-cost and high-performance optical printing head, is presented. The a-Si:H TFT driver consists of inverter circuits, switch TFTs, and matrix circuits. A block driving method was employed to compensate for the low operating speed of the a-Si:H TFTs. The 256-dot, 300-dot/in resolution prototype device mounted in a printing head shows an over-30 contrast ratio and an 8-page/min operating speed. Additional measurements on this device demonstrate the possibility of operation with a 24-page/min speed at a 600 dot/in resolution. >

A novel ferroelectric liquid-crystal (FE-LC) shutter array with a poly-Si thin-film-transistor (TFT) driver has been fabricated which has 256 dots (300 dots/in. resolution) and is 21.7 mm long. The TFT driver is capable of driving the FE-LC in the static mode and reduces the number of outlet electrodes. This results in a device with the advantages of high contrast ratio (over 20 to 1), compact device size, and low cost. >