Littérature scientifique sur le sujet « Francesco Spinelli »

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

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

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

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

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.

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

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

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

Cuore della ricerca, sono le operazioni di “tassello”, così definite dall’architetto Franco Bonaiuti, ovvero quegli innesti chirurgici, quegli interventi puntuali di ricostruzione, all’interno del tessuto storico, o comunque ormai consolidato, della città. Se infatti le sperimentazioni architettoniche più complete e pianificate, di cui ben si conoscono intenti programmatici, esiti formali e successive critiche, riguardano i quartieri periferici di espansione di Firenze, e sono legate soprattutto ai vari enti preposti allo sviluppo delle residenze collettive convenzionate, sono altrettanto interessanti, ma sicuramente meno noti, i casi di edilizia privata, di elevato valore architettonico, che punteggiano il tessuto del centro storico e l’immediato intorno dei viali di circonvallazione. Lezioni che ci fanno riflettere sul mestiere di architetto, quando non è semplice pratica professionale, ma è invece un bagaglio di conoscenze che hanno riferimenti con la cultura del tempo, per cui anche un lavoro di edilizia diventa un’opera di architettura.

Few other semantic fields pervade Plato’s oeuvre, from the earliest to the latest works, in such a definitive and ambivalent way as that of mimesis. From the philosophy of language to aesthetics and moral psychology, from metaphysics to cosmology and theology: in a strikingly large array of philosophical subject areas, the semantics of mimesis have crucial significance in Plato. The conference volume “Platonic Mimesis Revisited” offers a comprehensive and context-sensitive re-examination of mimesis in all relevant dialogues. Unlike earlier monographic studies, it brings together a considerable variety of scholarly perspectives from Philosophy and Classics, thus providing a broad tableau of modern approaches to the topic.With contributions byMichele Abbate, Alexandra V. Alván Leon, Laura Candiotto, Andrea Capra, Elenio Cicchini, Michael Erler, Francesco Fronterotta, José Antonio Giménez Salinas, Stephen Halliwell, Irmgard Männlein-Robert, Lidia Palumbo, Anna Pavani, Julia Pfefferkorn, Antonino Spinelli, Benedikt Strobel and Justin Vlasits.