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Belgioioso, Giulia. "Les racines suaréziennes de la métaphysique cartésienne : La lecture des Principia de Francesco Maria Spinelli (1733)/ Suarezian roots of Cartesian metaphysics: Francesco Maria Spinelli's reading of the Principia philosophiae." Revue d'histoire des sciences 58, no. 1 (2005): 123–44. http://dx.doi.org/10.3406/rhs.2005.2239.
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Ceccarelli, F., F. Natalucci, C. Perricone, E. Cipriano, C. Pirone, G. Olivieri, T. Colasanti, et al. "FRI0159 EROSIVE ARTHRITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS: APPLICATION OF CLUSTER ANALYSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 663–64. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4245.
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Background:Systemic Lupus Erythematosus (SLE) related arthritis has been traditionally defined non-erosive and then considered a minor manifestation. Thanks to the application of more sensitive imaging techniques, such as ultrasonography (US), erosive damage has been identified in up to 40% of SLE patients with joint involvement, suggesting the need for more appropriate treatment (1). Antibodies directed against citrullinated and carbamilated proteins (ACPA and anti-CarP, respectively) have been associated with erosive damage and then proposed as biomarkers for this more aggressive phenotype (2).Objectives:Here, we evaluated a large SLE cohort with joint involvement by using cluster analysis, in order to identify the disease phenotype associated with erosive arthritis.Methods:For this analysis, we enrolled consecutive SLE patients (ACR 1997 criteria) with a clinical history of joint involvement (arthritis/arthralgia). Clinical and laboratory data were collected in a standardized computerized electronically filled form, including demographics, past medical history with the date of diagnosis, co-morbidities, previous and concomitant treatments, serological status. The presence of rheumatoid factor (RF), ACPA and anti-CarP was investigated by ELISA test. Erosive damage was assessed by ultrasonography at level of metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints (MyLab Eight Exp, Esaote, Florence, Italy). Data have been analysed by hierarchic cluster analysis (SPSS program, IBM).Results:We enrolled 203 patients [M/F 12/191, median age 46.0 years (IQR 18); median disease duration 120.0 months (IQR 108)]. Erosive damage was identified in 53 patients (26.1%), all of them referring at least one episode of arthritis during disease course. Moving on autoantibodies status, RF was positive in 29.5%, anti-CarP in 28.5% and ACPA in 11.2%. The univariate analysis demonstrated a significant association between US-detected erosive damage and anti-CarP (p=0.01), ACPA (p=0.03), and renal manifestations (p=0.03). In Figure 1 we reported the dendrogram obtained from cluster analysis, allowing the identification of four cluster. Positivity for ACPA, anti-CarP, erosive damage, Jaccoud’s arthropathy and renal manifestations were allocated in the same cluster. Interestingly, RF resulted allocated in a different cluster, including ENA, anti-SSA and anti-SSB antibodies.Conclusion:The application of cluster analysis allowed the identification of a specific SLE phenotype, characterized by erosive damage, renal manifestations and positivity for anti-CarP and ACPA. We could speculate about the presence of a shared pathogenic mechanism, involving NETosis, contributing to nephritis and erosive arthritis.References:[1]Ceccarelli F et al. Semin Arthritis Rheum 2017[2]Ceccarelli F et al. Arthritis Res Ther 2018Disclosure of Interests:Fulvia Ceccarelli: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, enrica cipriano: None declared, Carmelo Pirone: None declared, Giulio Olivieri: None declared, Tania Colasanti: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Ceccarelli, F., G. Olivieri, L. Dominici, A. I. Celia, E. Cipriano, C. Garufi, S. Mancuso, et al. "OP0204 LUPUS COMPREHENSIVE DISEASE CONTROL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: APPLICATION OF A NEW INDEX." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 127.1–127. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4560.
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Background:The main outcomes in SLE patients management are represented by the remission achievement and chronic damage prevention. Even though activity and damage are intimately connected, to date indices including both these outcomes are not available.Objectives:In the present study, we aimed at assessing the application of a new index, the Lupus comprehensive disease control (LupusCDC), including disease activity and chronic damage progression.Methods:We performed a longitudinal analysis, including SLE patients according to ACR 1997 criteria, followed-up in the period between January 2014 and December 2018, and with at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated, as reported in Table 1 (1).Table 1.Remission levels considered in the study (1).Remission levelDefinitionComplete Remission(CR)No clinical and serological activity (SLEDAI-2K=0) in corticosteroid-free and immunosuppressant-free patients (antimalarials allowed)Clinical remission off-corticosteroids(ClR-GCoff)Serological activity with clinical quiescent disease according to SLEDAI-2K in corticosteroid-free patients (stable immunosuppressive therapy and antimalarials allowed)clinical remission on-corticosteroids(ClR-GCon)Clinical quiescent disease according to SLEDAI-2K in patients on prednisone 1–5 mg/day (stable immunosuppressants and antimalarials allowed)Chronic damage was registered according to SLICC damage index (SDI). All the patients were evaluated at baseline (T0) and every 12 months (T1, T2, T3, T4). At each time-point, we calculated the prevalence of LupusCDC, defined as remission achievement plus absence of chronic damage progression in the previous one year. We calculated this outcome including separately the different remission levels.Results:According with inclusion criteria, 172 SLE patients were evaluated in the present analysis [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. At first assessment, we observed a mean±SD SDI value of 0.7±1.1. In details, 56 patients (32.5%) showed damage in at least one organ/system and the presence of damage was significantly associated with age (p<0.0001, r=0.3) and disease duration (p=0.0003, r=0.3). During the follow-up, we observed a significant increase in SDI values compared with T0 (T1: mean±DS 0.8±1.3, p<0.0001; T2: 0.8±1.4, p<0.0001; T3: 0.9±1.4 p=0.0001; T4: 1.0±1.5 p<0.0001).In figure 1A and 1B we reported the proportion of patients achieving the different levels of remission and LupusCDC, respectively. In particular, the LupusCDC definition including CR was the most frequently detected in all time-points evaluated (T1: 18.0%; T2: 31.9%; T3: 27.9%; T4: 24.4%), with a significant difference at T2 [LupusCDC(CR)versusLupusCDC(ClR-GCoff), p=0.0002; LupusCDC(CR)versusLupusCDC(ClR-GCon) p=0.0002)], T3 [LupusCDC(CR)versusLupusCDC(ClR-GCoff), p=0.03; LupusCDC(CR)versusLupusCDC(ClR-GCon) p=0.006], T4 [LupusCDC(CR)versusLupusCDC(ClR-GCon), p=0.002]. No significant differences were found when comparing the prevalence of different remission levels and the prevalence of LupusCDC including the corresponding remission.Conclusion:In the present analysis we proposed for the first time a new index including disease activity and chronic damage, in order to evaluate the proportion of SLE patients reaching a comprehensive disease control. We found that CR is most frequently associated with the absence of damage progression.References:[1]Zen M et al. Ann Rheum Dis 2017.Disclosure of Interests:Fulvia Ceccarelli: None declared, Giulio Olivieri: None declared, Lorenzo Dominici: None declared, Alessandra Ida Celia: None declared, enrica cipriano: None declared, Cristina Garufi: None declared, Silvia Mancuso: None declared, Francesco Natalucci: None declared, Valeria Orefice: None declared, Carlo Perricone: None declared, Carmelo Pirone: None declared, viviana antonella pacucci: None declared, Francesca Morello: None declared, Simona Truglia: None declared, Francesca Miranda: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Orefice, V., F. Ceccarelli, C. Barbati, R. Lucchetti, G. Olivieri, E. Cipriano, F. Natalucci, et al. "THU0227 CAFFEINE INTAKE MODULATES DISEASE ACTIVITY AND CYTOKINES LEVELS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 340.2–341. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2100.
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Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Cazden, Courtney B., and Charles Haynes. "School discourse problems. Danielle N. Ripich & Francesca M. Spinelli (Eds.). San Diego: College-Hill, 1985. Pp. xiii + 279." Applied Psycholinguistics 7, no. 4 (December 1986): 394–96. http://dx.doi.org/10.1017/s0142716400007761.
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Ariani, A., E. Bravi, M. De Santis, V. Hax, S. Parisi, F. Lumetti, F. Girelli, et al. "OP0063 QUANTITATIVE COMPUTED TOMOGRAPHY PREDICTS 10-YEAR MORTALITY IN INTERSTITIAL LUNG DISEASE RELATED TO SYSTEMIC SCLEROSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 42.1–42. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2239.
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Background:Interstitial lung disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Chest CT is the gold standard in detecting ILD although it is not easy to understand its prognostic value. ILD qualitative assessment is almost worthless. Goh et al. semi quantitative score of ILD extent is related to mortality risk but it is burdened by relevant inter/intra-readers variability. An operator independent algorithm based on voxel-wise analysis proved to identify SSc patients with an increased risk of mortality according to prediction models.Objectives:To verify if quantitative analysis of chest CT (QCT) predict 10 years-mortality in SSc patients.Methods:SSc patients with availability of a chest CT were enrolled in 13 different centers. The CT voxel-wise analysis with a free software (www.horosproject.com) provided QCT indexes: kurtosis, skewness, mean lung attenuation and standard deviation. Patients characteristics, autoimmune profile and pulmonary function test were collected. The follow-up interval lasted from the date of chest CT to the one of the last visit or death. Each QCT index cutoff, established in a previous study (1), clustered patients in two groups. Kaplan-Meier analysis estimated and compared survival in the above mentioned groups. p < 0.05 was considered statistically significant.Results:Five hundred sixty three SSc patients were enrolled (35938 patient-months); 52.4% had ILD detectable at CT scan. For each QCT index cutoff the cohort was split in two subgroups without differences in terms of sex, age, disease duration, autoimmune profile. All QCT indexes’ cutoff selected subgroups with statistically different survival rate (e.g in Figure 1).Figure 1Conclusion:QCT can arise as the new gold standard in identifying SSc patients with poor prognosis. The real possibility to stratify SSc subjects according mortality risk will have a pivotal role in ILD treatment decisional process with the incoming anti-fibrotic drugs.References:[1]Ariani A et al. Rheumatology 2017Disclosure of Interests:Alarico Ariani: None declared, Elena Bravi: None declared, Maria De Santis: None declared, Vanessa Hax: None declared, Simone Parisi: None declared, Federica Lumetti: None declared, Francesco Girelli: None declared, Marta Saracco: None declared, Fabio De Gennaro: None declared, Alessandro Giollo: None declared, Masen Abdel Jaber: None declared, Francesco Bozzao: None declared, Mario Silva: None declared, Maria Chiara Ditto: None declared, Claudia Lomater: None declared, Flavio Mozzani: None declared, Daniele Santilli: None declared, eleonora Di Donato: None declared, Andrea Becciolini Speakers bureau: Sanofi-Genzyme, UCB and AbbVie, Francesco Pucciarini: None declared, Lorenzo Canziani: None declared, Flavio Cesare Bodini: None declared, eugenio arrigoni: None declared, M Bredemeier: None declared, Rafael Mendonça da Silva Chakr: None declared, Amelia Spinella: None declared, Luca Idolazzi: None declared, Roberto Bortolotti: None declared, Paola Tomietto: None declared, Elisa Baratella: None declared, Saverio Tollot: None declared, Dilia Giuggioli: None declared, Fabio Fischetti: None declared, Enrico Fusaro: None declared, Nicola Sverzellati: None declared, Carlo Alberto Scirè: None declared
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Alexandre, Gabriel Guimarães. "O papel da memória discursiva em manchetes que desmentem notícias sobre Covid-19." Scripta 25, no. 54 (November 30, 2021): 68–95. http://dx.doi.org/10.5752/p.2358-3428.2021v25n54p68-95.
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A pandemia de Covid-19 trouxe-nos um contexto de exceção. Restrições impostas à sociedade foram aplicadas por governos de diferentes partes do mundo, gerando dificuldades, por exemplo, de escolha entre ter privacidade de dados ou saúde prometida por vigilância biométrica (HARARI, 2020). Como “resposta” à disseminação de fake news – não só sobre a doença, mas também sobre outros temas – as agências de fact-checking (PANGRAZIO, 2018; SPINELLI, SANTOS, 2018) surgem com o objetivo de verificá-las, classificando-as em “verdadeiras” ou “falsas”, segundo gradação. Quando publicam a checagem realizada, as agências utilizam manchetes que desmentem as notícias. Entre os padrões linguísticos observados, a negação é bastante frequente nas manchetes verificadas em mídias sociais. Por ser um índice de implícito, está presente no enunciado para produzir sentido: a memória discursiva é, pois, um modo de compreender o estatuto dos implícitos (ACHARD, 1999; PÊCHEUX, 1999). Logo, partimos da hipótese de que a prática de estruturar a negação, nas manchetes analisadas, pode fazer emergir questões interlocutivas via evocação de certa memória discursiva. Com base em pressupostos teórico-metodológicos dos estudos de letramentos (New Literacy Studies) e da Análise do discurso francesa, este trabalho objetivou analisar o papel da memória discursiva em 68 manchetes, publicadas em março de 2020 por duas agências (“Chequeado” e “Agência Lupa), as quais desmentem notícias sobre Covid-19 em mídias sociais. Os resultados obtidos permitiram identificar três estruturas de negação frequentes nas manchetes e parecem confirmar a hipótese de partida, contribuindo com os estudos de letramentos, quanto à formação do leitor em tempos de pandemia.
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Olivieri, G., F. Ceccarelli, A. Lo Presti, S. Angeletti, C. Perricone, G. Iaiani, L. De Florio, et al. "THU0281 EXPLORING THE GENETIC DIVERSITY OF STAPHYLOCOCCUS AUREUS IN PATIENTS AFFECTED BY SYSTEMIC LUPUS ERYTHEMATOSUS: ASSOCIATION WITH DISEASE-RELATED FEATURES AND ACTIVITY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 367.1–368. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3592.
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Background:Infective factors play a central role in autoimmune diseases pathogenesis. It is possible to speculate that the host genotype could interact with genetic background of infective agents. We previously evaluated a large SLE cohort, observing the association between theS. Aureus(SA) carriage status and presence of a more active disease in terms of autoantibodies positivity.Objectives:We evaluated epidemiological, molecular characterization, genetic diversity and evolution of SA isolated from SLE patients by means of phylogenetic analysis.Methods:Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate phylogenetic relationships and to assess significant clades in patients with persistent carriage status (nasal swab positive in two consecutive evaluation, performed 1 week apart). The first dataset was composed by seven SA tuf gene isolated from non-SLE individuals from different countries (downloaded from the GenBank database,https://www.ncbi.nlm.nih.gov/nucleotide/) and tuf gene SA collected from SLE patients enrolled in the present study.Results:We enrolled 118 patients (M/F 10/198; median age 45.5 years, IQR 13,2; median disease duration 120 months, IQR 144). Skin involvement is the most frequent disease manifestation (86 patients, 72.9%), followed by joint involvement (78 patients, 66.1%). Twenty-four patients (20.3%) were SA carriers (SA+), three of them resulted MRSA. SA+ patients showed a significantly higher prevalence of joint involvement (79.2%versus62.7%, P=0.01) and anti-dsDNA positivity (75.0%versus55.3%, P=0.004). Moreover, SA+ SLE showed a more active disease, in terms of SLEDAI-2k values [SA+: median 2 (IQR 3.75)versusSA-: median 0 (IQR 2), P=0.04). The phylogenetic analysis has been restricted on the 21 non-MRSA SA+ patients. The maximum likelihood phylogenetic tree of the first dataset revealed a statistically supported larger clade (A, N=17) and a smaller one (B, N=4; figure 1A). SLE patients located in the clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P<0.0001) and SA- (62.7%, P<0.0001, figure 2B). Moreover, haematological manifestations were significantly more frequent in clade A patients (64.7%) compared with B (50.0%, P=0.004, figure 2C).Conclusion:The results of the present study confirmed the association between SA carriage status and disease activity, in terms of SLEDAI-2k values and anti-dsDNA positivity. The phylogenetic analysis ontufgene show a clustering ofSA+patients in two major clade (A and B). Interestingly thetufgenotype of clade A is significantly associated with a specific disease phenotype, characterized by joint involvement and positivity for anti-dsDNA. These findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.References:[1]Rigante et al. Int J Mol Sci. 2015;[2]Wertheim et al Lancet Infect Dis. 2005;[3]Conti et al Arthritis Res Ther 2016;[4]Tong et al Clin Microbiol Rev. 2015;[5]Rhee et al Infect Control Hosp Epidemiol. 2015Disclosure of Interests:Giulio Olivieri: None declared, Fulvia Ceccarelli: None declared, Alessandra Lo Presti: None declared, silvia angeletti: None declared, Carlo Perricone: None declared, Giancarlo Iaiani: None declared, Lucia De Florio: None declared, francesca antonelli: None declared, Luigino Amori: None declared, Cristina Garufi: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, cristiano Alessandri: None declared, Guido Valesini: None declared, Massimo Cicozzi: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Natalucci, F., F. Ceccarelli, E. Cipriano, G. Olivieri, C. Perricone, F. R. Spinelli, S. Truglia, et al. "THU0627-HPR JOINT INVOLVEMENT SIGNIFICANTLY INFLUENCES QUALITY OF LIFE OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 557–58. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3791.
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Background:Joint involvement is one of the most common features observed in Systemic Lupus Erythematosus (SLE), potentially involving up to 90% of patients [1]. Several patients’ reported outcomes (PROs) have been employed to measure Quality of life (QoL) in SLE patients, but frequently not specifically developed for SLE patients. More recently, the LupusQoL has been validated, a disease specific questionnaire[2,3].Objectives:We focused at assessing the relationship between musculoskeletal manifestations and QoL in a large SLE cohort, by using the LupusQoL.Methods:SLE patients with a clinical history of joint involvement (arthralgia/arthritis – group A) were enrolled in the present study. SLE diagnosis was performed according to the revised 1997 ACR criteria. As a control group, we enrolled SLE patients without history of joint involvement (group B).Disease activity was assessed by the SLE Disease Activity Index-2000 (SLEDAI-2k). The activity of joint involvement was assessed by using the disease activity score on 28 joints (DAS28ESR). The LupusQoL was administered to the enrolled patients (Group A and Group B). It consists of 34 items referring to eight domains: physical health (PH), pain (P), planning (PL), intimate relationships (IR), burden to others (BO), emotional health (EH), body image (BI) and fatigue (F).Results:Group A included 110 patients [M/F 8/102; median age 49 years (IQR 13), median disease duration 156 months (IQR 216)], while group B included 58 patients [M/F 11/47; median age 40 years (IQR 15), median disease duration 84 months (IQR 108)]. Group A showed a significantly lower disease duration and mean age in comparison with group B (P< 0.001 for both comparisons). As represented in figure 1, group A showed significantly lower values in all LupusQoL domains except for “burden to others” domain. Moreover, we observed an inverse correlation between DAS28ESRand all the LupusQoL domains in group A patients [PH (r=-0.5, P>0.0001), P (r=-0.5, P<0.0001), PL (r=-0.5, P<0.0001), IR (r=-0.2, P=0.006), BO (r=-0.4, P=0.0004), EH (r=-0.3, P=0.0009), BI (r=-0.4, P=0.001), F (r=-0.4, P<0.0001)]. Conversely, SLEDAI-2k values inversely correlated only with PL (r=-0.3, P=0.006), IR (r=-0.25, P=0.02), EH (r=-0.3, P=0.02).Figure 1.Conclusion:In the present study, by using a disease specific PRO, we found a poorer QoL in SLE patients with joint involvement in comparison with those without this manifestation. Moreover,DAS28ESRsignificantly correlated with all LupusQol domains, differently from SLEDAI-2k, suggesting the need to evaluate joint involvement with a specific activity index.References:[1]Cervera R et al. Medicine 1993[2]McElhone K. et al. Arthritis Rheum 2007.[3]Conti F et al. Lupus 2014Group (A)Group (B)pPH80,38 ± 21,4362,88 ± 23.28< 0.0001P82,36 ± 25.0862,30± 26.02< 0.0001PL83,04 ± 27.8270,58± 29.450.001IR84,49± 25.9965,36± 36.330.0005BO69,58 ± 28.4663,45± 28.950.129EH71,98 ± 24.6964,69± 23.050.0169F73,69 ± 24.2959,78±26.060.0004B78,14 ± 24.6156,28±30.14<0.0001Disclosure of Interests:Francesco Natalucci: None declared, Fulvia Ceccarelli: None declared, enrica cipriano: None declared, Giulio Olivieri: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Simona Truglia: None declared, Francesca Miranda: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Guido Valesini: None declared
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Barbati, C., F. R. Spinelli, C. Garufi, I. Duca, F. Ceccarelli, T. Colasanti, M. Vomero, C. Alessandri, G. Valesini, and F. Conti. "AB0085 MODULATION OF CIRCULATING SKELETAL STAMINAL CELLS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1342–43. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4314.
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Background:Rheumatoid arthritis (AR) is an autoimmune systemic inflammatory disease characterized by chronic synovial inflammation resulting in bone damage and erosions, with consequently functional disability. Currently, attempts for regenerative therapies for osteo-cartilage pathologies have proved unsuccessful. Recently, a “pool” of skeletal stem cells (hSSCs: human skeletal stem cells) able to generating bone cells, has been identified in human bone (1).Objectives:In light of these observations, we aim at characterizing skeletal stem cells in peripheral blood from RA patients candidate to Tofacitinib treatment.Methods:In this pilot study 4 RA patients [4F; mean age 65 years; mean disease duration 19 years] candidate to Tofacitinib treatment and 4 healthy donors (HD), matched by gender and age, were enrolled. Blood samples were collected from each subject of the study, at baseline (T0) and for RA patients, after 1 month of Tofacitinib (T1), to evaluatinghSSC(CD45-, CD146-, CD73+, PDPN+, CD164+) by flow cytometry. For this purpose, we performed on whole blood a negative magnetic selection for CD45 cells. Then, the eluate was labeled with antibodies anti CD146-PE, anti CD73-APC, anti CD164 - FITC and anti-Podoplanin (PDPN) PerCP/Cyanine5.5. The acquisition was performed using a FACS Calibur, which included 100,000 events per sample (Figure 1).Results:ThehSSCspercentage was significantly lower in RA patients than in HD (p = 0.0286). At T1, after treatment with Tofacitinib, meanhSSCspercentage significantly increased from 1.8% to 4.2 % (p = 0.016 vs RA T0) (Figure 2A). Correlation analysis showed a significant indirect relation between the percentage ofhSSCand disease activity measured by DAS28ESR, SDAI and CDAI (Figure 2B).Conclusion:The results of this study demonstrate, for the first time, circulating skeletal stem cells and their reduced expression in active RA patients. Tofacitinib treatment leads to a significant increase inhSSCspercentage. This evidence opens up new perspectives on bone repair mechanisms and on deepening of current therapeutic strategies.References:[1]Chan CKF, Gulati GS, Sinha R, Tompkins JV, Lopez M, Carter AC, Ransom RC, Reinisch A, Wearda T, Murphy M, Brewer RE, Koepke LS, Marecic O, Manjunath A, Seo EY, Leavitt T, Lu WJ, Nguyen A, Conley SD, Salhotra A, Ambrosi TH, Borrelli MR, Siebel T, Chan K, Schallmoser K, Seita J, Sahoo D, Goodnough H, Bishop J, Gardner M, Majeti R, Wan DC, Goodman S, Weissman IL, Chang HY, Longaker MT.Identification of the Human Skeletal Stem Cell.Cell. 2018 Sep 20;175(1):43-56.e21. doi: 10.1016/j.cell.2018.07.029.Acknowledgments:noneDisclosure of Interests:cristiana barbati: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristina garufi: None declared, Ilaria Duca: None declared, fulvia ceccarelli: None declared, Tania Colasanti: None declared, Marta Vomero: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Pacucci, V. A., C. Barbati, F. R. Spinelli, F. Ceccarelli, S. Mancuso, C. Garufi, C. Alessandri, and F. Conti. "AB0355 EFFECT OF TOFACITINIB IN TREG /TH17 BALANCE IN RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1477.2–1478. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4403.
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Background:Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that can cause progressive articular destruction (1). The imbalance between Tregs and Th17-cells - an effector T-cell subset acting as Treg antagonists – is closely linked to autoimmunity (2). A shift in the Th17/Treg balance towards the pro-inflammatory Th17 side has been reported in many autoimmune disorders including RA (4-5). Tofacitinib is the first janus kinases (JAK) inhibitor (JAKi) approved for the treatment of RA and it binds to and competitively inhibits the kinase domain of JAK3, JAK1 and, to a lesser degree, JAK2. Data on JAKi and Th17 cells/regulatory T cells (Tregs) are only available for ruxolitinib, a JAKi registered for myeloproliferative diseases (6).Objectives:Our project aimed at investigate the possible effect of Tofacitinib on the Treg/Th17 balance in RA patients.Methods:We isolated Peripheral Blood Mononuclear Cells (PBMCs) from patients affected by RA at baseline (T0) and after one month of Tofacitinib therapy (T1). By flow cytometry we characterized Treg and Th17 at T0 and T1. Clinical and laboratory data of the patients were collected in a standardized, computerized and electronically filled form. We assessed the disease activity by using DAS-28 (CRP). Data were expressed as mean(SD) or median (interquartile range, IQR) according to the variables’ distribution. Mann-Whitney and Spearman test were used. The values of P < 0.05 were considered statistically significant.Results:We isolated PBMCs from 9 patients with RA (F:M = 7:2, mean age±SD 60±17.4 years; mean disease duration±SD 20±6.6 years, DAS-28 median at T0 4.14 IQR 1.6; at T1 3.08 IQR 1.3). The median percentage of Treg and Th17 at T0 and T1 were respectively: T0 1.85 IQR 0.98 T1 3.12 IQR 1.37; T0 1.64 IQR 1.4, T1 0.6 IQR 1.1. Treg significantly increased after tofacitinib treatment while Th17 showed a tendency in decreasing without achieving a statistical difference (p= 0.003 and p=0.8, respectively) (figure 1). DAS-28 was negatively correlated with Treg number (r = -0.76565, p = 0.00021) and positively with Th17 numbers (r = 0.5816, p = 0.01135).Conclusion:This is the first study that investigated the role of JAKi on the Treg/Th17 balance in RA showing and increase in Treg cells with a concurrent tendency in decrease of Th17 cell population. The restore of the Treg/Th17 balance was associated with the reduction of DAS-28 (CRP).References:[1]McInnes IB et al. Lancet 2017[2]Fasching P et al. Molecules 2017[3]Han L et al. Front. Med. 2015[4]Beringer A et al. Med. 2016[5]Lippert E et al. Blood 2006Disclosure of Interests:viviana antonella pacucci: None declared, cristiana barbati: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fulvia Ceccarelli: None declared, Silvia Mancuso: None declared, Cristina Garufi: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Garufi, C., F. Ceccarelli, F. R. Spinelli, S. Mancuso, C. Pirone, and F. Conti. "POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 583. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3850.
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Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos
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Lucchino, B., M. Leopizzi, T. Colasanti, V. DI Maio, C. Alessandri, G. Valesini, F. Conti, M. DI Franco, and F. R. Spinelli. "FRI0376 EFFECT OF CARBAMYLATED LOW-DENSITY LIPOPROTEINS ON BONE CELLS HOMEOSTASIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 784.2–785. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2741.
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Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 μg/ml, 100 μg/ml and 200 μg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 μg/ml p=0,0015) and nLDL treated cells (200 μg/ml p= 0,011; 20 μg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 μg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (p<0.05) (Fig 3). nLDL did not affect the ALP expression. Treatment with cLDL stimulated RANKL mRNA expression in osteoblasts increasing the RANKL/OPG ratio (Fig 4).Fig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly
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Pacucci, V. A., F. R. Spinelli, K. Giannakakis, S. Colafrancesco, S. Truglia, F. Ceccarelli, C. Garufi, C. Alessandri, and F. Conti. "SAT0223 TUBULO-INTERSTITIAL INFILTRATES IN LUPUS NEPHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1054.1–1055. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1296.
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Background:Lupus nephritis (LN) occurs in up to 60% of patients affected by Systemic Lupus Erythematosus (SLE). The presence of inflammatory infiltrates in glomeruli and/or in tubulo-interstitium (TI) plays an important role in terms of prognosis (1). Ectopic lymphoid structures (ELSs) are clusters of organized lymphoid infiltrates forming at sites of chronic inflammation in non-lymphoid organs (2). Data on ELSs in kidneys of SLE patients are scant (3-5).Objectives:The aim of the study was to evaluate the tubule-interstitial infiltrates (TI-I) organization and to investigate the presence of ELSs.Methods:Kidney sections of SLE patients undergoing a renal biopsy for diagnostic purpose were studied; LN was diagnosed according to the 2003 International Society of Nephrology / Renal Pathology Society classification criteria. Clinical, laboratory and histological data were collected in a standardized, computerized and electronically filled form, including past medical history. The presence of lymphoid aggregates and ELS in the kidney sections were firstly evaluated by hematoxylin-eosin (HE). By using immunohistochemistry (IHC), we characterized the infiltrates by identification of T cells (CD3), B cells (CD20) and follicular dendritic cells (CD21).Results:By HE we evaluated 53 kidney samples from LN patients (F:M = 51:2, mean age at biopsy ± SD years 35±7.7; mean disease duration at date of biopsy ± SD 8±8.3 years). TI-I were found in 33 kidney specimens. By HE we identified a well-defined infiltrate pattern resembling ELS in 13 renal samples. In these samples, we confirmed the presence of organized infiltrates by IHC, with evidence of segregated T and B cells areas in most of them. In one sample, the CD21 staining was positive confirming the presence of ELS (Figure 1). Interestingly, this last patient, who failed ciclophosphamide and mycofenolate, responded to rituximab administration and is now in complete LN remission. Moreover TII was negatively correlated with renal remission after induction therapy (P=0.03) independent of the histological class and the induction treatment.Figure 1.Biopsy specimens showing tubulo-interstitial ELS by IHC (10x).Conclusion:Assessment and management of LN patients are greatly facilitated by information obtained by renal biopsy. In the present study the evaluation by HE of 53 kidney samples from patients with LN showed TI-I in 62% of the specimens and a well-defined infiltrate pattern with GC-like features in 39% of those specimens with TI-I, confirmed in IHC. The presence of TII was associated with a worse outcome in response to therapy. Our preliminary results obtained by IHC suggest that ELS could be considered as a biomarker of renal response to B-cell depleting therapy supporting the importance of TI disease.References:[1]Giannakakis K. & Faraggiana T. Histopathology of Lupus Nephritis. Clinic Rev Allerg Immunol 2011[2]Bombardieri M et al. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol 2017[3]Chang A et al. In situ B cell-mediated immune responses and tubulointerstitial inflammation in human lupus nephritis. J Immunol 2011[4]Shen Y et al. Association of intrarenal B-cell infiltrates with clinical outcome in lupus nephritis: a study of 192 cases. Clin Dev Immunol 2012[5]Neusser MA et al. Intrarenal production of B-cell survival factors in human lupus nephritis. Mod Pathol 2011Disclosure of Interests:viviana antonella pacucci: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Konsantinos Giannakakis: None declared, Serena Colafrancesco: None declared, Simona Truglia: None declared, Fulvia Ceccarelli: None declared, Cristina Garufi: None declared, cristiano alessandri Grant/research support from: Pfizer, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Cipriano, E., F. Ceccarelli, F. R. Spinelli, C. Garufi, I. Duca, S. Mancuso, C. Alessandri, et al. "SAT0555 MUSCULOSKELETAL ULTRASOUND IN MONITORING RESPONSE TO JAKi IN RHEUMATOID ARTHRITIS PATIENTS: RESULTS FROM A LONGITUDINAL STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1235–36. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5987.
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Background:Therapeutic approach of rheumatoid arthritis (RA) patients has been enriched by the introduction of small molecules. In particular Jak inhibitors (JAKi), baricitinib and tofacitinib, demonstrated their efficacy in patients naïve or resistant to biological treatments in randomized controlled trials. Moreover, these drugs seem to be able to prevent radiographic progression. To date few data are available from the real life context. Ultrasonographic (US) assessment has became a valid imaging tool in the management of RA patients in clinical practice, allowing the evaluation of joint inflammatory status. Together with clinimetric assessment, US could provide a comprehensive assessment of drug response.Objectives:In the present study we aimed at assessing the early response to JAKi treatment by using musculoskeletal US.Methods:In this prospective longitudinal study, we collected data about all consecutive active RA patients starting treatment with JAKi. RA was diagnosed according to the 2010 ACR/EULAR criteria. At each visit, clinical and laboratory data were collected in a standardized and computerized form, including demographics, past medical history, co-morbidities, previous and concomitant treatments. According with study protocol, all patients underwent clinical and US assessment at the following time-points: baseline (T0), 4 weeks (T1) and 12 weeks (T2). Clinical evaluation included tender and swollen joint counts (0-28), patients global health assessment. C-reactive protein (CRP) levels were registered and disease activity was calculated by disease activity score (DAS) in 28 joints by using CRP (DAS28-CRP). A systematic multiplanar grey-scale and power Doppler (pD) US examination was performed by using MyLab Eight Exp Machine (Esaote, Florence, Italy) at level of 22 joints (bilateral I-V metacarpophalangeal, I-V proximal interphalangeal, wrist). According with OMERACT definitions (1) we assessed the presence of synovial effusion, hypertrophy and pD, that were scored according to a semi-quantitative scale (0-3). A total US inflammatory score (0-198) was obtained by their sum.Results:We enrolled 91 patients [F/M 77/14; median age 60.0 years (IQR 15.5); median disease duration 144 months (IQR 126)]. Of these patients, 54 (59.3%) were treated by baricitinib and the remaining 37 by tofacitinib. At baseline we found a median US inflammatory score of 20 (IQR 18.7) and a median DAS28-CRP of 5.0 (IQR 1.56). US assessment demonstrated significant reduction in the median values of inflammatory score already at T1 [median 13 (IQR 14.7), p<0.0001], that was maintained at T2 [median 10 (IQR 11), p<0.0001]. These results are represented in figure 1. Similar to US inflammatory score, a significant reduction was registered for DAS28-CRP median values [T1 3.5 (IQR 1.73), p<0.0001; T2 3.3 (IQR 1.8), p<0.0001]. No significant differences were found when subgrouping patients according with different JAKi drug, in terms US and clinimetric assessment.Conclusion:In the present study, specifically designed to evaluate the US-detected efficacy of JAKi in RA patients, we demonstrated in a real life setting a significant, early and sustained improvement of inflammatory joint status.References:[1]Wakefield et al, J Rheumatol 2005Disclosure of Interests:enrica cipriano: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Cristina Garufi: None declared, Ilaria Duca: None declared, Silvia Mancuso: None declared, cristiano alessandri Grant/research support from: Pfizer, Manuela Di Franco: None declared, Roberta Priori: None declared, Valeria Riccieri: None declared, Rossana Scrivo: None declared, Carlo Perricone: None declared, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Pirone, C., F. Ceccarelli, A. Selntigia, C. Perricone, S. Truglia, V. A. Pacucci, F. R. Spinelli, et al. "SAT0228 PREGNANCY OUTCOME IN SYSTEMIC LUPUS ERYTHEMATOSUS: A MONOCENTRIC COHORT ANALYSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1056.1–1057. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3106.
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Background:Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease, affecting prevalently women in childbearing age. Thanks to pre-gestational counseling and multi-disciplinary approach, adopted in daily clinical practice, SLE patients are experiencing even more uncomplicated pregnancies.Objectives:Here, we evaluated pregnancy outcome in a large SLE cohort, compared to a control group including pregnant women without autoimmune diseases.Methods:Pregnant SLE patients (diagnosis made according to ACR 1997 criteria) were included in the present study, conducted in the context of a joint rheumatology/gynecology multi-disciplinary team. For each patient we collected demographic information, medical history, treatments, disease activity (SLEDAI-2K) chronic damage (SLICCdamage index), clinical and laboratory data, including serum complement level and autoantibodies. Pregnancy outcomes were reported longitudinally as well as disease relapses occurring during pregnancy and puerperium. Flares were defined as new onset or worsening disease-related manifestation in any organ/system.Results:Since 2008, 70 consecutive pregnancies occurred in 50 SLE patients [(median age at diagnosis 25 years (IQR 12.2), median age at first pregnancy 33 years (IQR 7), median disease duration 72 months (IQR 120)]. As controls, we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases [(median age 31 years (IQR 9)]. Table 1 reports the obstetric, fetal and neonatal outcomes of SLE patients compared to control group. A positive outcome in terms of live born infants was experienced in 88.6% of SLE pregnancies and in 88% of control group (p=NS). There were no statistically significant differences in any of the pregnancy outcomes evaluated; however, the percentage of small for gestational ages (SGA) was significantly higher in SLE group (22.8%versus11.0% P=0.003). A statistical association was found between SGA and positivity for anti-dsDNA, anti-SSA ed anti-SSB (p=0.0001, p=0.01, p=0.04 respectively). Miscarriage was significantly associated with disease-related serologic abnormalities [anti-dsDNA (p=0.0001), low C3 (p=0.0001) and low C4 (p=0.006)] and past smokinghabitus(p=0.0001); preterm birth was associated with anti-dsDNA, anti-CL and anti-B2GPI (p=0.001, p=0.0005, p=0.01 respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium (44.3%). Figure 1 reports SLE relapses divided according to organ involvement. Flare during pregnancy was associated with positivity for anti-SSA (p=0.001), anti-SSB (p=0.01) and a-CL (p=0.006), whilepuerperiumrelapses were associated with previous renal involvement (p=0.0005), flare during pregnancy (p=0.01) and chronic damage (p=0.0001).Table 1.Pregnancy outcomes in 50 SLE and 100 controls.LES(Pregnancies N=70)Controls(Pregnancies N=100)POBSTETRIC OUTCOMEPreterm birth N/%18/25.719/19NSGestational hypertension N/%5/7.13/3NSGestational diabetes N/%5/7.15/5NSPre-eclampsia N/%2/2.91/1NSFETAL OUTCOMEMiscarriages N/%8/11.412/12NSPR interval elongation N/%4/6.4––IUGR N/%3/51/1NSNEONATAL OUTCOMESGA< 10° centile N/%16/22.811/110.003Weight at birth median-I.Q.R.2850-6883250-8140.003Apgar 1’ median-I.Q.R.8-18-1NSApgar 5’ median-I.Q.R.9-110-1NSFigure 1.Disease flares during and after 70 SLE pregnancies divided according to organ involvement.Conclusion:The present study confirms the role of pre-gestational counseling and a multi-disciplinary approach in the outcome of SLE pregnancies. Moreover, the high prevalence of disease relapse even more justifies the need for a combined rheumatology/gynecology multi-disciplinary approach.Disclosure of Interests:Carmelo Pirone: None declared, Fulvia Ceccarelli: None declared, Aikaterini Selntigia: None declared, Carlo Perricone: None declared, Simona Truglia: None declared, viviana antonella pacucci: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Giuseppina Perrone: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Cacciapaglia, F., A. Manfredi, G. Erre, E. Bartoloni Bocci, G. Sakellariou, O. Viapiana, S. Colella, et al. "THU0257 ESTIMATED 10-YEARS CARDIOVASCULAR RISK IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: PRELIMINARY RESULTS FROM THE “CARDIOVASCULAR OBESITY AND RHEUMATIC DISEASE (CORDIS)” STUDY GROUP OF THE ITALIAN SOCIETY OF RHEUMATOLOGY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 355.2–356. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6187.
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Background:Systemic lupus erythematosus (SLE) patients are at high risk for CV events, and EULAR recommends assessing the 10-year CV-risk using the Systematic Coronary Risk Evaluation (SCORE) [1]. The QRISK3, another score to assess CV-risk in UK population, considers different factors among which also SLE. The Progetto Cuore score (PCS) is validated to estimate CV risk in Italian people and largely replicates the SCORE project [2].Objectives:This cross-sectional study aimed to estimate CV-risk using SCORE, QRISK3 and, for the first time, PCS in a multicentric cohort of Italian SLE patients.Methods:During 2019 we evaluated 173 SLE patients (87.7% female; age 40±16 years; disease duration 138±105 months), fulfilling the 1997 ACR classification criteria. Clinical and laboratory data were registered, and individual CV-risk was calculated using suitable algorithms for the SCORE, QRISK3 and PCS. Statistical analysis was performed using Graphpad Instat 8.0 (San Diego, CA-USA).Results:In 13 (7%) SLE patients a previous CV event was recorded. Hypertension was present in 60 (37.5%) and diabetes in 27 (16.9%) patients. Mean total cholesterol was 184±39 mg/dL, HDLc 58±18 mg/dL, LDLc 124±37 mg/dL, triglycerides 105±63 mg/dL; dyslipidaemia was reported in 58 (36.2%) patients and 29 (18.1%) were on statin. Mean BMI was 24.9±5.3 Kg/sm, 60 (37.5%) and 23 (14.3%) patients were overweight and obese, while 25 (15.6%) patients were smokers. 87 (54.3%) SLE patients had a SLEDAI<4, 91% of patients were taken HCQ and 65% were on prednisone (mean dose 5.4±5.9 mg/day), but only 7.5% took >7.5 mg/day. The CV-risk of SLE patients according to SCORE, QRISK3 and PCS was 1.1±2.1%, 10.5±12.3% and 3.7±5.4%, respectively. Stratifying patients at low, moderate or high CV risk according to the PCS and SCORE a double proportion of patients was at moderate (8% vs 3.9%) or high (1.9% vs 0.9%) CV risk (p=0.03). Finally, CV-risk according to QRISK3 was higher than 20% (high risk) in 32/160 (20%) patients.Conclusion:This multicentre study demonstrated that the mean estimated CV-risk in SLE patients is globally low using the SCORE, QRISK3 and PCS. The PCS seems to better intercept those patients at moderate/high risk, at least in Italian SLE patients, while QRISK3 predicts the highest CV risk. The lack of disease-specific CV-risk factors (such as autoantibodies profile or organ involvement) probably account for the underestimation of CV risk using the SCORE and PCS.References:[1]ARD 2019;78(6):736-745.[2]ARD 2019;0:1–2.doi:10.1136/annrheumdis-2019-215715Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Andreina Manfredi: None declared, Gianluca Erre: None declared, Elena Bartoloni Bocci: None declared, Garifallia Sakellariou Speakers bureau: Abbvie, Novartis, MSD, Ombretta Viapiana: None declared, Sergio Colella: None declared, Anna Abbruzzese: None declared, Marco Fornaro: None declared, Giacomo Cafaro: None declared, Maria Antonietta Fenu: None declared, Bianca Lucia Palermo: None declared, Martina Dessì: None declared, Adalgisa Palermo: None declared, Alessandro Giollo: 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, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fabiola Atzeni: None declared, Matteo Piga: None declared
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Mancuso, S., S. Truglia, S. Recalchi, G. Riitano, F. R. Spinelli, F. Ceccarelli, M. Sorice, C. Alessandri, and F. Conti. "FRI0145 FOLLOW-UP OF A MONOCENTRIC COHORT OF SERONEGATIVE ANTIPHOSPHOLIPID SYNDROME." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 656.1–657. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2928.
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Background:Seronegative antiphospholipid syndrome (SN-APS) is the term proposed to describe patients with clinical signs highly suggestive of APS but persistently negative for conventional antiphospholipid antibodies (aPL) assays. Therefore, new antigenic targets or different methodological approaches have been investigated to detect aPL in SN-APS [1].Objectives:The aim of this study was to describe the clinical follow-up of a monocentric cohort of SN-APS patients.Methods:The study included all consecutive SN-APS patients examined from 2014 to 2018. In all patients other possible causes of thrombosis or obstetric morbidity were ruled out. APL were investigated through two tests: 1. anti-cardiolipin/vimentin antibodies (aCL/Vim) by enzyme-linked immunosorbent assay (ELISA) 2. anti-cardiolipin antibodies (aCL) by thin-layer chromatography (TLC)-immunostaining.Results:We enrolled 121 patients (all Caucasian except one Asian and one Hispanic women). Clinical and demographic characteristics are reported in Table 1.Table 1.Clinical and demographic characteristicsFeaturesSN-APSn= 121 (%)Male/Female14/107Mean age in years (from-to)42.58 (16-78)PAPS/SAPS78/43 (64.5/35.5)SLE28 (23.1)Others autoimmune diseases15 (12.4)Pregnancy morbidity56/107 (52.3) Spontaneous abortions49 (45.8) Normal fetus deaths22 (20.6) Premature births7 (6.54)Thrombosis72 (59.5) Arterial thrombosis36 (29.8) Venous thrombosis48 (39.7) Recurrent thrombosis28 (23.1)Thrombosis + Pregnancy morbidity8 (6.6)Non-criteria APS features45 (37.2) Livedo reticularis18 (14.9) Thrombocytopenia12 (9.9) Migraine19 (15.7) Seizures5 (4) Others11 (9)Cardiovascular risk factors50 (41.3) Hypercholesterolemia8 (6.6) Smoking22 (18.2) Hypertension22 (18.2) OC/HRT7 (5.8) Diabetes4 (3.3)Sixty-nine out 121 patients (57%) resulted positive for at least one non-conventional test in two occasions more than 12 weeks apart (Figure 1). The agreement between first and second test resulted respectively of K=0,703 e K=0,655 (Cohen’s K test). Figure 2 shows the prevalence of aCL (TLC-immunostaining) and aCL/Vim. We found a significant correlation between aCL (by TLC-immunostaining) and aCL/Vim (p= 0.027), brain MRI ischemic changes (p= 0.012) and age (p= 0.023). ACL/Vim was significantly correlated with livedo reticularis (p = 0.015).Patients with double positivity showed a higher prevalence of mixed thrombotic and obstetrical features than patients with single positivity (p < 0.001, likelihood positive ratio 8.2).Non-conventional aPL positivity better supported the diagnosis of APS and, following the therapeutic changes implemented, in a median follow up of 41 months (IQR 39.5) only 3 cases of recurrent thrombosis (2 cases of arterial thrombosis during treatment with antiaggregant therapy and one case of venous thrombosis in treatment with new oral anticoagulant therapy) were observed. During the follow-up, 35 patients with obstetric morbidity who resulted positive for the tests had 20 pregnancies; 12 of them (60%) experienced a good outcome under conventional treatment for classical APS.Conclusion:The results demonstrate that new methods – TLC-immunostaining – or new antigens - CL/Vim – allow to detect aPL in so-called “SN-APS” patients and, consequently, to prescribe the most appropriate therapy.References:[1]Conti F et al. The Mosaic of “Seronegative” Antiphospholipid Syndrome. J Immunol Res. 2014;2014:389601Disclosure of Interests:Silvia Mancuso: None declared, Simona Truglia Speakers bureau: Lilly, BMS, Serena Recalchi: None declared, Gloria Riitano: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fulvia Ceccarelli: None declared, Maurizio Sorice: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Garufi, C., F. R. Spinelli, S. Mancuso, F. Ceccarelli, and F. Conti. "AB0704 TELEMEDICINE AT THE TIME OF COVID-19: THE EXPERIENCE WITH RA PATIENTS TREATED WITH JAK-INHIBITORS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1384.1–1384. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3892.
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Background:The spread of COVID-19, the lockdown, the limited access to care reevaluated the role of tele-consultation and self-assessment.Objectives:Our aim was to evaluate in a cohort of Rheumatoid Arthritis (RA) patients treated with JAK-inhibitors (JAKi): the self-assessed disease activity during lockdown, the lockdown impact on fatigue, anxiety, depression and the prevalence of Covid-19.Methods:We enrolled RA patients treated with baricitinib or tofacitinib. At baseline (BL) and follow-up we collected: patients’ demographic data, composite disease activity indices (CDAI, DAS28CRP), global assessment (PGA), pain visual analogue scale (VAS), FACIT (functional assessment of chronic illness therapy) and a self-rating scale for disease impact on anxiety and depression (Zung-A/D). Patients were instructed on how to perform self-assessment through video-material and fulfilled the online form of “Rheumatoid Arthritis Impact of Disease” (RAID)1 and “RA Disease Activity Index” (RADAI). To capture the pandemic effect, we compared patients in different status (remission, low, moderate and high-disease activity) at the last in-person visit (preCoV) through the DAS28CRP and CDAI, to the tele-health visit (THV), measured by the RAID. BL and pre-CoV ZUNG-A, ZUNG-D, FACIT questionnaires were compared with the online results during the pandemic. Exposure, tests and symptoms of Covid-19 were recorded. Data were expressed as mean±standard deviation or median(IQR) according to distribution.Results:Twenty patients (median age 58.2±11.9 and mean disease duration 153.5 ± 112.7 months) were treated with tofacitinib and 27 with baricitinib. The median time-lapse between the pre-CoV visit and the THV was 12 (IQR 4) weeks. DAS28CRP and CDAI significantly decreased from BL to pre-CoV visit. During the last in-person visit, 21 patients (48.83%) were in remission, 9 (20.93%) in low disease activity; according to the RAID, 15 (31.91%) and 7 (14.89%) patients were respectively in remission and low disease activity during the THV (Table A). PGA and pain significantly decreased from BL to pre-Cov visit but worsened during the lockdown (Table A). FACIT remaining stable during THV. At THV, we detected a significant improvement of anxiety from BL (Zung-A) and a tendency to lower depression scores compared to BL (Table A). JAKi showed a good safety profile considering Covid-19 symptoms, none of the patients was diagnosed with SarsCoV2 infection.Conclusion:This is the first study on virtual assessment in RA patients treated with JAKi. The unique social experiment of the pandemic impaired the clinical response already achieved before the lockdown, without a collateral worseling of FACIT, anxiety and depression.References:[1]Gossec L, et al. Ann Rheum Dis. 2009[2]Stucki G, et al. Arthritis Rheum. 1995Table A.DAS28, CDAI, RAID scores and patient-reported outcomes assessment at baseline and during the follow-upBLpre-CoVTHVDISEASE ACTIVITYN (%)N (%)N (%)REMISSIONDAS280 (0%)21 (48.8%)CDAI0 (0%)10 (22.7%)RAID15 (31.9%)LOW DISEASEDAS281(2.1%)9 (20.9%)CDAI7(14.8%)23 (52.2%)RAID7 (14.9%)MODERATEDAS2833 (70.2%)12 (27.9%)CDAI17 (37.1%)8 (18.1%)RAID13 (27.6%)HIGHDAS2813 (27.6%)1 (2.3%)CDAI23 (48.9%)3 (6.8%)RAID12 (25.5%)GH70 (30)20 (49.5)*45 (45)*#Pain70 (28)25 (45.5)*40 (48.5)*#Zung A37 (9)37 (10.2)35 (14)*Zung-D39 (17)39 (13)*38 (12)FACIT11.5 (17.2)8 (19.5)7(15)* p≤0.001 vs BL# p ≤0.04vs preCoVData expressed as median (IQR)Disclosure of Interests:Cristina Garufi: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Fulvia Ceccarelli: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos
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Campochiaro, C., G. De Luca, M. G. Lazzaroni, G. Armentaro, A. Spinella, B. Vigone, B. Ruaro, et al. "POS0890 NINTEDANIB REAL-LIFE EFFICACY AND SAFETY IN SYSTEMIC SCLEROSIS (SSc)-INTERTISTIAL LUNG DISEASE (ILD): AN ITALIAN MULTICENTRE PRELIMINARY STUDY." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 741.2–742. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3183.
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BackgroundNintedanib (NTD) has been approved for Systemic Sclerosis (SSc)-Interstitial Lung Disease (ILD) following the positive results of the SENSCIS trial.Objectivesto describe the efficacy and safety of NTD in SSc-ILD in a real-life setting.MethodsThe clinical data of SSc-ILD patients treated with NTD from 10 Italian SSc centres were retrospectively evaluated at baseline, 6 and 12 months: SSc clinical features, NTD tolerability, pulmonary function tests (PFTs) and modified Rodnan skin score (mRSS) were recorded.Results69 SSc-ILD patients (22 males [32%], mean age 60±12 years, disease onset 50±13 years, 4 [6%] anti-centromere, 53 [77%] anti-topoisomerase I, 3 [4%] anti-RNA-polimerase III) were identified. The vast majority (84%) was previously treated with immunosuppressants: 27 (39%) cyclophosphamide, 45 (65%) mycophenolate mofetil, 6 (9%) methotrexate, 9 (13%) azathioprine, 6 (9%) tocilizumab and 22 (32%) rituximab. In 11 (16%) patients, NTD was the first treatment for SSc-ILD. At baseline, 57 patients (83%) were on corticosteroids (mean daily prednisone dose 6±5 mg), 58 (84%) on immunosuppressants, 47 (68%) on mycophenolate mofetil, 14 (20%) on rituximab, 3 (4%) on tocilizumab, 2 on methotrexate (3%) and 1 (1%) on azathioprine. At baseline HRCT showed UIP pattern in 27 (39%) and NSIP pattern in 42 (61%) patients. The modifications of PFTs and mRSS over time are shown in Table 1. Since NTD introduction, gastro-intestinal (GI) side effects were recorded in 34 (49%) patients, with diarrhoea being the most common complaint (35%), followed by nausea/vomiting (23%) and weight loss (16%). In 21 (30%) patients, after a mean time of 2.6±3.4 months, NTD was maintained after dose adjustment. In 5 (7%) patients NTD was stopped after a median time of 5 (1-6) months due to subocclusion and persistent diarrhoea in 3 patients, untreatable nausea and vomiting in one patient and liver toxicity in 1 patient. During the follow-up after a median time of 10 (6 – 33) months, 4 patients died.Table 1.Pulmonary function tests and mRSS at baseline, 6 and 12 months in SSc-ILD on NTD.Baseline6 monthsP valueBaseline12 monthsP valueFVC (% predicted)64 ± 1865 ± 18 (33 pts)0.63870 ± 1969 ± 18 (20 pts)0.586TLC (% predicted)64 ± 1561 ± 14 (27 pts)0.15464 ± 1465 ± 18 (16 pts)0.944DLCO (% predicted)40 ± 1741 ± 18 (29 pts)0.66040 ± 1838 ± 18 (20 pts)0.304mRSS9 ± 68 ± 6 (26 pts)0.0027 ± 48 ± 6 (15 pts)0.334pts= patientsConclusionOur preliminary data confirm that in a real-life clinical scenario NTD, in combination with immunosuppressants, may stabilize PFT. However, despite the fact that GI side effects are frequent, they may be controlled with NTD dose adjustment thus retaining the drug in SSc-ILD patients. The NTD efficacy on skin involvement needs to be thoroughly evaluated on a larger SSc population.Disclosure of InterestsCorrado Campochiaro Speakers bureau: Boeboehringer ingelheim, Giacomo De Luca Speakers bureau: boehringer ingelheim, Maria Grazia Lazzaroni Grant/research support from: boehringer ingelheim, Giuseppe Armentaro: None declared, Amelia Spinella: None declared, Barbara Vigone: None declared, Barbara Ruaro: None declared, Anna Stanziola: None declared, Devis Benfaremo: None declared, Enrico De Lorenzis: None declared, Francesco Benvenuti: None declared, Silvia Laura Bosello Speakers bureau: boehringer ingelheim, Gianluca Moroncini: None declared, Giovanna Cuomo: None declared, Marco Confalonieri: None declared, Lorenzo Beretta: None declared, Elisabetta Zanatta: None declared, Dilia Giuggioli: None declared, Nicoletta Del Papa: None declared, Paolo Airò: None declared, Lorenzo Dagna: None declared, Marco Matucci-Cerinic Speakers bureau: boehringer ingelheim
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Oliviero, F., F. Galuppini, A. Scanu, P. Galozzi, V. Lazzarin, P. Sfriso, G. Ravagnan, et al. "OP0174 POLYDATIN PREVENTS CALCIUM PYROPHOSPHATE CRYSTAL-INDUCED ARTHRITIS IN MICE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 108.1–109. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2124.
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Background:Acute calcium pyrophosphate (CPP) crystal-induced inflammation is characterized by the massive release of cytokines and pro-inflammatory mediators and, from a clinical point of view, pain and limited joint function. Contrary to the precipitation of urate crystals that can be prevented through the use of hypouricemic drugs, there is no pharmacological therapy that can prevent the formation of pyrophosphate crystals.Polydatin (PD),a natural precursor of resveratrol, is a stilbenoid mainly contained in grape juice and bark of Polygonum Cuspidate. Its antioxidant, anti-inflammatory and immunomodulating properties have been demonstrated in several experimental models. We have recently shown that this compound is able to prevent the inflammatory response to pathogenic crystals in vitro (1).Objectives:The aim of this study was to assess the anti-inflammatory preventing effect of polydatin in the mouse model of acute crystal-induced arthritis.Methods:A suspension of sterile CPP crystals (0.3 mg/20 μL PBS) have been injected intra-articularly (i.a.) into one ankle joint of Balb/c mice under isoflurane anesthesia. Animals were randomized in 5 groups: 1- CPP injection, 2- CPP + PD, 3- CPP + colchicine (control drug), 4- CPP + vehicle (control. N 1), 5- PBS injection (control N. 2). Polydatin and colchicine were administered by gavage (respectively 40 mg/kg and 1mg/kg in 200 μL PBS/EtOH/glucose) at 24, 15 and 1 h before and 1, 6 and 24 h after (prophylactic model) or 1, 6 and 24 h after (therapeutic model) i.a. injection of CPP crystals.Ankle swelling was measured at different time points using a precision caliper. After 48h (peak of the acute phase) mice were euthanized and blood and ankle joints were collected for inflammatory cytokine (IL-1ß and KC) determination and histological analysis, respectively.Results:The mean change in ankle swelling after i.a injection was 0.595±0.434 mm. Prophylactic treatment with PD and colchicine significantly diminished ankle swelling to 0.175±0.115 mm and 0.137±0.100 mm, respectively (Kruskal Wallis p 0.0025; Dunn’s post test p < 0.01 CPP vs PD+CPP). The therapeutic administration of PD did not have significant effects on delta swelling (0.468±0.372 mm - PD vs 0.243±0.152 mm - colchicine). In mice treated with CPP crystals, histological analysis revealed areas of edema and increased cell infiltrate in articular and periarticular tissues and the presence of reactive lymphnodes. Tissue necrosis around inflamed tissue has been observed. Treatment with PD importantly reduced cell infiltrate in the prophylactic but not in the therapeutic protocol.Serum IL-1ß and KC levels, which increased significantly (p<0.05) after 48h from i.a injection, diminished in non significant manner after prophylactic and therapeutic treatment. The gene expression study revealed a reduction of IL-1ß and KC mRNA after PD and colchicine treatment in both groups.Conclusion:PD can effectively prevent acute inflammatory response to crystals in the mouse model of CPP arthritis. Oral PD prophylactic treatment showed a similar effect of colchicine in reducing ankle swelling and cell infiltrate. However, only colchicine showed to be effective in the therapeutic protocol.These results raise the possibility that PD might have utility in the prevention of crystal-induced acute attacks in humans.References:[1]Oliviero F, et al. Polydatin and resveratrol inhibit the inflammatory process induced by urate and pyrophosphate crystals in thp-1 cells.Foods 2019 Nov 7;8(11). pii: E560.Disclosure of Interests:Francesca Oliviero: None declared, Francesca Galuppini: None declared, Anna Scanu: None declared, Paola Galozzi: None declared, Vanni Lazzarin: None declared, Paolo Sfriso: None declared, Gianpietro Ravagnan: None declared, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, Paolo Spinella: None declared, LEONARDO PUNZI: None declared, Gianmaria Pennelli: None declared, Roberto Luisetto: None declared
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Andreoli, L., S. Alivernini, A. Alunno, S. L. Bosello, C. Chighizola, P. Conigliaro, E. Gremese, et al. "AB1265 GENDER DISTRIBUTION AND GENDER-RELATED ISSUES AMONG YOUNG RHEUMATOLOGISTS AND ACADEMIC POSITIONS IN RHEUMATOLOGY: A SNAPSHOT OF THE CURRENT SITUATION IN ITALY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1924.1–1924. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3123.
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Background:The Italian Society for Rheumatology (SIR) comprises committees for Rheumatologists under the age of 40 (SIRyoung) and for Women in Rheumatology (Reumatologhe Donne – ReDO). As female representation is increasing in rheumatology worldwide [1], there has been interest in assessing gender-related issues.Objectives:To describe the gender distribution among young members of SIR and academic positions in Rheumatology in Italy. To assess the expectations and needs of young rheumatologists with regard to their career.Methods:SIRyoung members developed a web-based survey which was distributed among SIR members under the age of 40 during the spring of 2019. Responses were collected and analysed anonymously. ReDO retrieved and analysed the data regarding academic positions in Italy in September 2019 from official data by “Ministry of Education, University and Research” (www.miur.it).Results:Out of 478 SIR members under 40 (66.5% F), 113 (23.7%) completed the SIRyoung survey (62.1% F). Regarding career plans, male and female members responded: hospital physician (36.9% vs 37.8%), outpatient clinic physician (18.5% vs 28.3%), academic career (23.9% vs 22.8%), private practice (16.3% vs 9.4%), and industry (4.3 vs 1.6%), respectively. When asked about their interest in doing a fellowship in another national center or abroad, 60.8% of male and 72.8% of female respondents were interested but thought they could not afford it. Reasons reported by males and females were: working reasons, namely barriers to temporarily leave the workplace (61.3% vs 50.7%), family reasons (16.1% vs 25.4%), financial reasons (22.6% vs 16.5%), respectively. As for academic rheumatology in Italy, 113 positions were retrieved. Men held 64 positions (57%) and women 49 (43%). Full professors were mostly men (92%), while assistant professors were women in 65% of the cases (58% of those with a permanent position; 72% of those with a temporary position) (Figure) [2].Conclusion:Our study explored for the first time gender distribution and related issues in Rheumatology in Italy. Female representation accounts for two thirds of SIR members under 40. This could reflect the general trend of medical school being chosen more often by women than men. No differences were observed in the career expectations of male and female rheumatologists. Interestingly, nearly one fourth of female respondents were interested in academic career, confirming the trend toward female predominance observed for assistant professors. Therefore, it is likely that the next generation of full professors will have a balanced gender distribution, as it is already for associate professors. The choice of a fellowship is still hampered by several problems, but it seems that reasons for not pursuing such opportunities are similarly distributed in males and females. Although family reasons tend to be more frequent in female rheumatologists, this is not significant as compared to men. This could indicate that family affects career choices of both male and female rheumatologists. It is important that national societies promote surveys for the assessment of gender specific issues among their members, in order to identify unmet needs and design interventions for career support regardless of gender.References:[1]Andreoli L, et al. Joint, Bone, Spine: Revue du Rhumatisme. 2019;86(6):669-672.[2]Bosello SL, et al. Reumatismo 2020; in press.Acknowledgments:SIRyoung and ReDO wish to thank the Steering Committee of SIRDisclosure of Interests:Laura Andreoli: None declared, Stefano Alivernini: None declared, Alessia Alunno: None declared, Silvia Laura Bosello: None declared, Cecilia Chighizola: None declared, Paola Conigliaro: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Cristina Iannuccelli: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Marta Vadacca: None declared, Maria Sole Chimenti: None declared
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Garufi, C., F. R. Spinelli, F. Ceccarelli, S. Mancuso, C. Barbati, T. Colasanti, C. Alessandri, and F. Conti. "AB0340 EFFECT OF BARICITINIB ON RANKL SERUM CONCENTRATION IN RHEUMATOID ARTHRITIS PATIENTS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1468.1–1469. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4399.
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Background:RANKL (receptor activator of nuclear factor κB ligand) and osteoprotegerin, the main regulators of bone metabolism, are involved in osteoblasts/osteoclasts balance in inflammatory disease, such as Rheumatoid Arthritis (RA). Janus kinase (JAK) inhibitors (baricitinib and tofacitinib) can reduce the progression of structural damage in patients with moderate to severe RA. Previous studies suggest a link between JAK inhibition, production of RANKL and osteoclastogenesis1,2.Objectives:to investigate the effect of baricitinib on RANKL serum concentration in unselected RA patients.Methods:Patients affected by RA according to 2010 ACR criteria, starting treatment with baricitinib as clinically indicated, were consecutively enrolled. Demographic, clinical and laboratory data were collected at baseline (T0) and after three months of therapy (T3). RANKL serum concentration was analyzed by ELISA at the same timepoints. All patients underwent ultrasound (US) examination at T0 and T3. According with OMERACT definitions, the presence of synovial effusion, hypertrophy and power Doppler were assessed and scored on a semi-quantitative scale (0=absent, 1=mild, 2=moderate, 3=severe), obtaining a total US score (0-198), representing the joint inflammatory status (15); erosions were registered. Data were expressed as median (interquartile range); Mann-Whitney and Spearman tests were performed for comparisons and p values < 0.05 were considered statistically significant.Results:We prospectively followed up 33 RA patients starting treatment with baricitinib [M/F 8/25; age 58(9) years; disease duration 165(150) months; 22/33 (67%) ACPA-anti-citrullinated protein antibody positive; 24/33 patients (73%) RF-rheumatoid factor positive]. After three months of therapy we observed a significant reduction of DAS28CRP, CDAI and SDAI compared to baseline (p<0.0001). The US inflammatory score showed a significant improvement at T3 (p<0.0001). The serum concentration of RANKL showed a significant decrease after three months of therapy from 44 (25.9) to 27.5 (35.3) pg/ml,p=0.0256 (Figure 1). While in 67% of patients RANKL decreased after treatment, in 33% of patients no decrease or an increase of RANKL was detected. Those patients showing an increase of RANKL had similar DAS28CRP, CDAI, SDAI, but had significantly less swollen joints, compared to those in which RANKL decreased (p=0.0364). At baseline, the concentration of RANKL significantly correlated with the swollen joint count (p=0.0117) and ESR (p=0.0482), but not with DAS28CRP, CDAI, SDAI nor with the US inflammatory score. Nevertheless, the reduction of RANKL was not significantly associated with the achievement of low disease/remission after three months of treatment, with ACPA/RF positivity or the presence of erosions detected by US.Conclusion:This is the first study demonstrating that baricitinib reducesin vivothe serum levels of RANKL, regardless the correlation with disease activity indices. The discrepancy between the levels of RANKL and the clinical response is in line with previous data in the literature, demonstrating that, under treatment with anti-TNF and anti-IL1, the decrease of RANKL did not influence the local or systemic inflammatory parameters, even if still preventing bone loss3.References:[1]LaBranche T P et al. JAK inhibition with tofacitinib suppresses arthritic joint structural damage through decreased RANKL production. Arthritis Rheum 2012[2]Murakami, KA Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro. PLOS ONE 2017[3]Stolina M et al. RANKL inhibition by osteoprotegerin prevents bone loss without affecting local or systemic inflammation parameters in two rat arthritis models: comparison with anti-TNFalpha or anti-IL-1 therapies. Arthritis Res Ther 2009Disclosure of Interests:Cristina Garufi: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Fulvia Ceccarelli: None declared, Silvia Mancuso: None declared, cristiana barbati: None declared, Tania Colasanti: None declared, cristiano alessandri Grant/research support from: Pfizer, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Duca, I., F. R. Spinelli, F. Ceccarelli, C. Garufi, S. Mancuso, C. Alessandri, R. Scrivo, et al. "FRI0121 STEROID-SPARING EFFECT OF JAK INHIBITORS IN RHEUMATOID ARTHRITIS PATIENTS FOLLOWED UP IN A REAL LIFE SETTING." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 641.2–642. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5998.
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Background:Glucocorticoids (GCs) are a milestone of Rheumatoid Arthritis (RA) treatment; EULAR recommendations on the management of medium to high dose glucocorticoids remind to evaluate comorbidities and risk factors for adverse events when planning GCs treatment. Tofacitinib and Baricitinib are Janus kinases inhibitors (JAKi) registered for RA treatment. About 60% of patients enrolled in randomized clinical trials with JAKi were co-treated with GCs; however, little is known about tapering and percentage of withdrawal both in clinical trials and real life.Objectives:To evaluate the steroid-sparing effect of JAKi in patients with RA.Methods:We prospectively enrolled consecutive adult patients with RA starting JAKi. At baseline and after 4, 12 and 24 weeks we calculated C-Reactive Protein based Disease Activity score 28 (DAS28CRP). Daily dose of GCs was recorded at each visit as prednisone (PDN)-equivalent dose. Data are expressed as median (IQR). Continuous variables were compared by Mann Whitney test while dichotomous ones by Chi-square test. P values < 0.05 were considered statistically significant.Results:Between January 2018 and January 2020, 108 patients started JAKi: 67 patients Baricitinib, 41 patients Tofacitinib. The analysis was restricted to 64 RA patients (50 female, 14 male) who had at least 6 months of follow-up. Table 1 shows the demographic, clinical and clinimetric characteristics of the cohort. Patients treated with baricitinib and tofacitinib were comparable for age, disease duration, PDN dose and previous number of csDMARDS and bDMARDS; 30 patients (47.6%) were treated with JAKi in monotherapy. At baseline, the median daily PDN dose was 5 (7.25) mg; after 4, 12 and 24 weeks the median daily dose significant decreased to 5 (6.25) mg, 2.5 (5) mg and 0 (5) mg, respectively (p<0.0001). The percentage of patients treated with GC decreased from 81.5% to 63.5% at week 4, and to 48.4% at week 12 and 24. After 4, 12 and 24 weeks we detected a significant reduction of DAS28 (p<0.00001 compared to baseline). A similar percentage of patients who withdrew PDN compared to those who were still on PDN achieved remission after 12 and 24 months. Similarly, the reduction in DAS28 was comparable between the two groups at week 4 [4.8 (4.2) in those who withdrew vs 4.1 (1) in those who did not] at week 12 [4.8(1.6) for both] and at week 24 [3.7 (1.4) in those who withdrew vs 2.3 (0.7) in those who did not].Table 1.Demographic, clinic and clinimetric characteristics of the 64 patientsBaricitinib= 41Tofacitinib=23P valueFemale:male33:817:6P=nsAge, median (IQR), years58 (15)66 (14.5)P=nsDisease duration, median (IQR), months144 (144)150 (120)P=nsN° of previous csDMARDS3 (3)3 (1)P= nsN° of previous bDMARDs2 (3)1 (3)P= nsDAS28CRPat baseline4.7 (1.6)4.8 (2)P=nsPDN dose at baseline, median (IQR), mg5 (7.5)5 (5)P=nsPDN dose at 4 weeks, median (IQR), mg5 (7.5)5 (5)P=nsPDN dose at 12 weeks, median (IQR), mg2 (5)2.5 (4.7)P=nsPDN dose at 24 weeks, median (IQR), mg0 (5)2.5 (0)P=nsIQR: interquartile range; DAS28CRP: Disease Activity Score 28 using C-Reactive Protein, csDMARDS: conventional synthetic Disease Modyfing anti-rheumatics drugs, bDMARDS: biotheconological Disease Modifying anti-rheumatics drugs PDN= prednisoneConclusion:The rapid reduction of disease activity determined by JAK inhibitors allows a fast tapering of PDN, as suggested by the last EULAR recommendations for the management of RA.Disclosure of Interests:Ilaria Duca: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fulvia Ceccarelli: None declared, Cristina Garufi: None declared, Silvia Mancuso: None declared, cristiano alessandri Grant/research support from: Pfizer, Rossana Scrivo: None declared, Roberta Priori: None declared, Valeria Riccieri: None declared, Manuela Di Franco: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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Garufi, C., G. Tucci, I. Pacella, M. Zagaglioni, A. Pinzon Grimaldos, F. Ceccarelli, S. Piconese, F. R. Spinelli, and F. Conti. "AB0087 THE EFFECT OF BARICITINIB ON STAT1 PHOSPHORYLATION IN MONOCYTES FROM RHEUMATOID ARTHRITIS PATIENTS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1175.1–1175. http://dx.doi.org/10.1136/annrheumdis-2022-eular.4332.
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BackgroundBaricitinib is a Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA)1-2. STAT proteins bind JAK kinase dimers coupled with cytokine receptors and regulate gene transcription. The JAK/STAT system is responsible for the intracellular signaling of different cytokines contributing to the activation process of the monocyte lineage, therefore the use of JAK inhibitors can affect cell functionality3-6.ObjectivesThe aim of the present study was to verify the effects of baricitinib on STAT phosphorylation in peripheral mononuclear cells (PBMCs) of RA patients and to evaluate any correlation between STAT phosphorylation and response to therapy.MethodsAt baseline (BL) and after 4 weeks (w4) of treatment, we evaluated patients’ disease activity (DAS28PCR, CDAI and SDAI), dividing them into responders and non-responders according to the Minimal Clinically Important Difference for DAS28PCR (1.2 points) at w4. The phosphorylation of STAT1, STAT4 and STAT5 was analyzed at BL and w4 in gated monocytes, Treg, CD8 + and CD4 + lymphocytes from 4 responder and 4 non-responder patients through flow cytometry, at basal conditions and after IL2, IFNα and IL6 stimulation.ResultsBaseline clinical and demographic characteristics of patients are reported in Table 1. We showed that monocyte count decreased from BL to w4 mostly in responders. Basal pSTAT1 phosphorylation tent to be higher in monocytes of non-responder patients; after 4 weeks of treatment, the reduction of the cytokine-induced pSTAT1 was significantly greater in monocytes from responders compared to non-responders (Figure 1). The phosphorylation of STAT4 and STAT5 was not affected by treatment in any cell type and at any time point. We further studied the STAT1 phosphorylation pathway isolating the effect of stimulation with IFNα and stratifying monocytes according to their surface marker expression of CD14 and CD16 in classical, intermediate and non-classical. We observed the same pattern with a significant greater reduction of pSTAT1 in monocytes from responder patients, compared to non-responders, after the treatment with baricitinib.Table 1.Clinical and demographic characteristics of Rheumatoid Arthritis patients.Clinical and demographic characteristicsN=8Age (years), median (IQR)59 (8)Female:Male7:1Etnicity-Caucasian n (%)6 (75)-Hispanic n (%)2 (25)Disease duration (months), median (IQR)156 (201)Rheumatoid Factor, n (%)3 (37.5)ACPA, n (%)4 (50)Number of previous csDMARDs, n (%)-12 (25)-21 (12.5)-31 (12.5)-≥ 44 (50)Number of previous bDMARDs, n (%)-12 (25)-22 (25)-31 (12.5)-≥ 43 (37.5)Baricitinib in monoterapy, n (%)5 (62.5)Daily PDN dose, median (IQR)5 (6)ACPA: anti-citrullinated protein antibodies; csDMARDs: conventional syntetic disease-modifying antirheumatic drugs; bDMARDs: biological disease-modifying antirheumatic drugs; PDN: prednisone.Figure 1.STAT1 phosphorylation in responder (R) and non-responder (NR) patients at basal conditions (before stimulation) (a), and after cytokine (IL2, IFNα and IL6) stimulation (b) at baseline and at T1 (week 4).ConclusionThese results may suggest that monocyte count and STAT1 phosphorylation in circulating monocytes could represent early markers of response to baricitinib therapy.References[1]Gadina M, et al. Janus kinases to jakinibs: from basic insights to clinical practice. Rheumatology (Oxford). 2019[2]Gadina M, et al. Translating JAKs to Jakinibs. J Immunol. 2020[3]Kubo S, et al. The JAK inhibitor, tofacitinib, reduces the T cell stimulatory capacity of human monocyte-derived dendritic cells. Ann Rheum Dis. 2014[4]Kubo S, et al. Janus Kinase Inhibitor Baricitinib Modulates Human Innate and Adaptive Immune System. Front Immunol. 2018[5]Ikari Y, et al. Peficitinib Inhibits the Chemotactic Activity of Monocytes via Proinflammatory Cytokine Production in Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Cells. 2019[6]Yang X, et al. Tofacitinib inhibits ox-LDL-induced adhesion of THP-1 monocytes to endothelial cells. Artif Cells Nanomed Biotechnol. 2019Disclosure of InterestsCristina Garufi Consultant of: Lilly, Gloria Tucci: None declared, Ilenia Pacella: None declared, Marta Zagaglioni: None declared, Alessandra Pinzon Grimaldos: None declared, Fulvia Ceccarelli: None declared, Silvia Piconese: None declared, Francesca Romana Spinelli Consultant of: Lilly, Fabrizio Conti Consultant of: Lilly
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De Martino, E., P. Conigliaro, M. S. Chimenti, P. Triggianese, S. L. Bosello, E. Gremese, C. Iannuccelli, F. R. Spinelli, M. Vadacca, and R. Perricone. "AB0679 HEALTH ASSESSMENT IN FEMALE PATIENTS WITH SPONDYLOARTHRITIS: FOCUS ON REPRODUCTIVE SPHERE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1634.2–1635. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4719.
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Background:SpA patients experience a decreased quality of life due to social, emotional and relational life impairment in addition to pain, fatigue and joint damage. Sexual dysfunction (SD) is often neglected by both patients and clinicians, although articular and extra-articular manifestations of the disease can decrease the quality of sexual life. Previous findings showed that SD can affect from 27% to 67% of patients with rheumatic diseases. Data available on SD in rheumatic patients are poor and primarily focus on male ankylosing spondylitis patientsObjectives:The aim of this study is to evaluate, in a group of female SpA patients, the presence of SD, its relationship with extra-articular manifestations and to estimate the correlation between disease activity and sexual activity.Methods:52 SpA patients (including PsA, IBD-SpA and undifferentiated SpA-un-SpA) and 50 healthy controls (HC) were administered the Female Sexual Function Index (FSFI) questionnaire for the analysis of sexual function (score from 0 to 100). SD is defined by a score lower than 26. Disease activity was evaluated through DAPSA and BASDAI. SpA-HAQ and BASFI was also performed to assess functional statusResults:There was a trend for a significantly greater proportion of SD in the patients (21%) than the controls (8%), χ2(1,N =102) = 3.52,p= .06). Within the different groups, the percentage of those with SD according to the FSFI cut off were 23% of PsA patients, 25% of IBD-SpA patients, 11% of un-SpA patients, and 8% of healthy controls, however, when the patient groups were analysed separately these differences were not significant, χ2(3,N =102) = 4.43,p= .22. Mean scores on the FSFI were lower for the total SpA patients group t(100) = 2.47, p = .02 compared to HC. When scores on the FSFI were analysed separately for each patient group, there was a trend for a significant difference between the groups,F(3,98) = 2.43,p= .07, and follow up t-tests showed that only the PsA group scored significantly lower than the HC,t(100) = 2.56,p= .01 (see Fig. 1). Among the items of the questionnaire, questions regarding sexual desire, lubrication and discomfort were statistically significantly lower scores in patients compared to HC (p= 0.001,p= 0.009,p= 0.02, respectively). For the overall patient group, the FSFI was significantly negatively correlated with the DAPSA (r= -.37,p= .008), the SpA-HAQ (r= -.30,p= .03) and the BASFI (r= -.30,p= .03). Additionally, the PsA group showed a negative correlation between DAPSA scores and FSFI score (r= -.38,p=.03) and the IBD-SpA group had a negative correlation between FSFI score and BASFI (r= -.80,p= .002).Conclusion:Overall, the data generally show that SD is more common in SpA patients compared to HC and that SpA patients score lower on the FSFI. The negative correlations between the FSFI and scores on DAPSA, SpA-HAQ and BASFI suggest that sexual function may be poorer for patients with greater disease activity and poorer functional status. These findings could be due to the number of tender and/or swollen joints as well as chronic pain or fatigue patients often experience. A key limitation of this study is the small sample size. Future research will include a larger sample size. SD in patients with rheumatic disease is still a neglected field in clinical practice, however, its assessment could contribute to improved quality of life for patientsTable 1.Clinical characteristics of patients and healthy controlsPsAun-SpAIBD-SpAHCAge (mean ± SD)50.6 ± 4.043.9 ± 3.646.3 ± 2-052.5 ± 0.5Distribution (N%)31 (59%)9 (17%)12 (24%)50Age at diagnosis (mean ± SD)40.0 ± 2.535.6 ± 4.140.8 ± 1.2/DAPSA15.1 ± 9.912.2 ± 9.9/HAQ0.6 ± 0.50.8 ± 0.51.0 ± 0.7/BASDAI0.6 ± 0.90.6 ± 0.85.1 ± 2.8/BASFI16 ± 16.037.8 ± 26.846.7 ± 21.7/Disclosure of Interests:erica de martino: None declared, Paola Conigliaro: None declared, Maria Sole Chimenti: None declared, Paola Triggianese: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, 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, Cristina Iannuccelli: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Marta Vadacca: None declared, Roberto Perricone: None declared
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De Brito, Rodrigo Pinto, and Rafael Huguenin. "Tradução de sexto empírico, ‘Contra os astrólogos’, 1-22." Prometheus - Journal of Philosophy, August 14, 2015. http://dx.doi.org/10.52052/issn.2176-5960.pro.v8i18.3945.
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Tradução grego-português de Sexto Empírico, Contra os astrólogos, 1-22 (= M V 1-22), a partir da fixação de Bekker (BEKKER, I. Sextus Empiricus [opera omnia]. Berlim: Typis et Imprensis Ge. Reimeri, 1842), adotando as emendas de H. Mutschmann (MUTSCHMANN, H. Sexti Empirici Opera. v. III. Leipzig: Bibliotheca Scriptorum Graecorum et Romanorum Teubneriana, 1912). Para cotejo, usamos a mui influente versão latina de Henri Estienne e Gentian Hervet (STEPHANI, H.; HERVET, G. Sexti Empirici Opera Graeca et Latini. Leipzig: Sumptu Librariae Kuehnianae, 1841), além da versão inglesa de R. G. Bury, a romena de A. M. Frenkian, as italianas de A. Russo e de E. Spinelli, a espanhola de J. B. Cavero e a francesa de P. Pellegrin, C. Dalimier, D. Delattre, J. Dellatre e B. Prérez.