Academic literature on the topic 'Edith Rothe'

Resumen En el presente artículo (i) se desarrolla una crítica al discurso histórico-filosófico de Kant para explicitar sus condiciones de posibilidad, desde lo cual se erige un modelo hermenéutico que (ii) hace inteligible la historia filosofante de la filosofía presente en Los progresos de la metafísica desde los tiempos de Leibniz y Wolff, mostrando cómo las condiciones operan allí y constituyen una determinada narrativa que da cuenta de las perspectivas desde las cuales se ofrece la historia; después (iii) se realiza la interpretación de la historia desde el modelo con el fin de señalar su sostenibilidad; al final, (iv) se vincula la historia filosófica con la propia filosofía trascendental de Kant, legitimando con ello al modelo y señalando cómo el horizonte del proyecto crítico es esa misma historia. Palabras clave Metafísica: Historia; Razón; Teleología; Discurso. Referencias Allison, Henry E., Kant’s Transcendental Idealism. An Interpretation and Defense, USA: Yale University Press, 2004. Allison, H. E., Editor’s Introduction, a What real progress has metaphysics made in Germany since the time of Leibniz and Wolff?, en Kant, Immanuel, Theoretical Philosophy after 1781, edit. Henry Allison, Peter Heath, Cambridge University Press, USA, 2002. Allison, Henry E., “General Introduction”, en Kant, Immanuel, Theoretical Philosophy after 1781, edit. Henry Allison y Peter Heath, USA: Cambridge University Press, 2002. Beiser, Frederick C., “Moral Faith and the Highest Good”, en The Cambridge Companion to Kant and Modern Philosophy, edit. Paul Guyer, USA: Cambridge University Press, 2006. Caimi, Mario, “La metafísica de Kant”, en Kant, Immanuel, Los Progresos de la metafísica desde los tiempos de Leibniz y Wolff, trad. Mario Caimi, México: Fondo de Cultura Económica, UNAM, UAM, 2011. Duque, Félix, “Estudio Introductorio”, en Kant, Immanuel, Los progresos de la metafísica, trad. Félix Duque, Madrid: Tecnos, 1987. Ferrarin, Alberto, The Powers of Reason. Kant and the Idea of Cosmic Philosophy, USA: University of Chicago Press, 2015. Grondin, Jean, Introduction to Metaphysics. From Parmenides to Levinas, trad. Lukas Soderstorm, USA: Columbia University Press, 2012. Guyer, Paul, “The Unity of Nature and Freedom”, en Guyer, Paul, Kant’s System of Nature and Freedom, USA: Oxford University Press, 2005. Heidegger, Martin, Kant y el problema de la metafísica, trad. Gred Ibscher Roth, México: Fondo de Cultura Económica, 1996. Kant, El conflicto de las facultades, trad. Roberto Rodríguez Aramayo, en Immanuel Kant, Kant III, España: Gredos, 2014. Kant, Immanuel, Idea para una historia universal en clave cosmopolita, trad. Roberto Rodríguez Aramayo, en Immanuel Kant, Kant III, España: Gredos, 2014. Kant, Immanuel, Crítica de la razón pura, trad. Mario Caimi, México: FCE, UNAM, UAM, 2011. Kant, Immanuel, Los progresos de la metafísica, trad. Mario Caimi, México: Fondo de Cultura Económica, UNAM, UAM, 2011. Kant, Immanuel, Conjectural beginning of human history, trad. Allen W. Wood, en Immanuel Kant, Anthropology, History and Education, edit. Gunter Zoller, Robert B. Louden, USA: Cambridge University Press, 2007. Kant, Immanuel, On the use of teleological principles in philosophy, trad. Gunter Zoeller, en Kant, Immanuel, Anthropology, History and Education, edit. Gunter Zoller, Robert B. Louden, USA: Cambridge University Press, 2007. Kant, Immanuel, On a recently prominent tone of superiority in philosophy, trad. Peter Heath, en Kant, Immanuel, Theoretical Philosophy after 1781, edit. Henry Allison, Peter Heath, USA: Cambridge University Press, 2002. Kant, Immanuel, Proclamation of the imminent conclusion of a treaty of perpetual peace in philosophy, trad. Peter Heath, en Kant, Immanuel, Theoretical Philosophy after 1781, edit. Henry Allison, Peter Heath, USA: Cambridge University Press, 2002. Kerszberg, Pierre, Critique and Totality, USA State University of New York Press, USA, 1997. Kuhen, Manfred, “Kant’s Critical Philosophy and its Reception –the first five yearse (1781-1786)”, en The Cambridge Companion to Kant and Modern Philosophy, edit. Paul Guyer, USA: Cambridge University Press, 2006. Leibniz, Gottfried, El método verdadero, trad. J. Echeverría, en Leibniz, Leibniz, España: Gredos 2014. Longuenesse, Béatrice, Kant and the Capacity to Judge. Sensibility and Discursivity in the Transcendental Analytic of the Critique of Pure Reason, trad. Charles T. Wolfe, USA: Princeton University Press, 1998. Lyotard, Jean-Francois, Enthusiasm. The Kantian Critique of History, trad. Georges Van Den Abbeele, USA: Standford University Press, 2009. Martínez Marzoa, Felipe, Historia de la filosofía antigua, Madrid: Akal, 1995. Martínez Marzoa, Felipe, Releer a Kant, España: Anthropos, 1989. Platón, Fedón, trad. Carlos García Gual, en Platón, Platón I, España: Gredos, 2014. Platón, Menón, trad. Francisco José Olivieri, en Platón, Platón I, España: Gredos, 2014. Sevilla, Sergio, “Kant: Razón histórica y razón trascendental”, en Kant después de Kant, edit. Javier Muguerza, Roberto Rodríguez Aramayo, Madrid: Tecnos, 1989. Spinoza, Baruch, Ética demostrada según el orden geométrico, trad. Oscar Cohan, México: Fondo de Cultura Económica, 2015. Tugendhat, Ernst, Introducción a la filosofía analítica, trad. José Navarro Pérez, España: Gedisa, 2003. Vieinard-Baron, Jean-Louis, Platón et l’idealisme allemande (1770-1830), Paris: Beauchesne, 1979. Vilar, Gerard, “El concepto del Bien Supremo en Kant”, en Kant después de Kant, edit. Javier Muguerza, Roberto Rodríguez Aramayo, Madrid: Tecnos, 1989. Zammito, John, The Genesis of Kant’s Critique of Judgment, USA: The University of Chicago Press, 1992.

Background:Rheumatoid arthritis (RA) has bene associated with atherosclerosis and cardiovascular (CV) disease. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is suitable to detect synovial and vascular inflammation. Tofacitinib has been used to effectively treat RA.Objectives:We wished to assess the effects of tofacitinib treatment on synovitis and vascular inflammation simultaneously by 18FDG-PET/CT.Methods:Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib and evaluated at baseline and after 6 and 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (aCCP) levels. All patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in order to determine vascular and synovial inflammation in five aortic segments and five articular regions, respectively. In the joints, mean (SUVmean) and maximum standard uptake values (SUVmax), while in the aorta, mean (TBRmean) and maximum target-to-background ratios (TBRmax) were determined. Carotid intima-media thickness (IMT), arterial stiffness (PWV) and endothelial dysfunction (FMD) were determined by ultrasound.Results:One-year tofacitinib treatment significantly attenuated vascular and synovial inflammation as visualized by PET/CT. Articular SUVmean (p=0.010), SUVmax (p=0.001), as well as aorta TBRmax (p<0.001) significantly decreased over time. Synovial inflammation as determined by PET/CT variably and positively associated with aCCP, RF, CRP, ApoB, lipoprotein A (LpA), IMT and PWV. Vascular inflammation (TBRmax) inversely correlated with HAQ and positively with ESR, ApoA, and PWV. Uni- and multivariable analyses suggested that articular SUV values were independently associated with CRP, ApoB, LpA, IMT and PWV, while aortic TBRmax was determined by HAQ and PWV.Conclusion:18F-PET/CT is suitable to simultaneously assess synovial and vascular inflammation in RA. One-year tofacitinib treatment dampened inflammation. PET/CT changes were associated with markers of systemic inflammation, atherogenic lipids, carotid atherosclerosis and arterial stiffness.References:[1]Gotthardt M, Bleeker-Rovers CP, Boerman OC, Oyen WJ. Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques. J Nucl Med. 2010;51(12):1937-49.[2]Bucerius J, Hyafil F, Verberne HJ, Slart RH, Lindner O, Sciagra R, et al. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis. Eur J Nucl Med Mol Imaging. 2016;43(4):780-92.Acknowledgements:This research was supported by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program’ (Z.S.); by the European Union grant GINOP-2.3.2-15-2016-00015 (G.P., G.T. and Z.S.) and by the Pfizer Investigator Initiated Research Grant no. WI188341 (Z.S.).Disclosure of Interests:Attila Hamar: None declared, Zsolt Hascsi: None declared, Anita Pusztai: None declared, Monika Czókolyová: None declared, Edit Végh: None declared, Zsófia Pethö: None declared, Katalin Gulyás: None declared, Boglárka Soós: None declared, György Kerekes: None declared, Éva Szekanecz: None declared, Katalin Hodosi: None declared, Sándor Szántó Speakers bureau: Abbvie, MSD, Novartis, Consultant of: Abbvie, MSD, Novartis, Gabriella Szücs Speakers bureau: Boehringer, Actelion, Roche, Consultant of: Boehringer, Actelion, Roche, Tamas Seres: None declared, Zoltán Szekanecz Speakers bureau: Abbvie, Pfizer, Roche, Novartis, Lilly, Sager, Janssen, Consultant of: Pfizer, Abbvie, Roche, Novartis, Grant/research support from: Pfizer, Szilvia Szamosi Speakers bureau: Roche

Background:Rheumatoid arthritis (RA) has been associated with increased cardiovascular (CV) risk and metabolic changes.Objectives:We wished to determine how the Janus kinase (JAK) inhibitor tofacitinib influences vascular pathophysiology and metabolites of the arginine and methionine-homocysteine pathways.Methods:Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib and evaluated at baseline and after 6 and 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (aCCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels.Results:Twenty-six patients completed the study. Tofacitinib treatment maintained FMD and PWV. Ten mg bid tofacitinib significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. Tofacitinib transiently increased L-citrulline and L-NMMA and decreased homocysteine levels after 12 months. Based on L-citrulline, L-ornithine, ADMA and SDMA levels, L-arginine remained highly available for endothelial NO production. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with aCCP. Regarding vascular pathophysiology, only PWV and methionine correlated with each other after 12 months.Conclusion:Tofacitinib suppressed systemic inflammation in RA yielding stabilization of vascular function. It may exert CV protective effects in RA, at least in part, by shifting L-arginine metabolism to high arginine availability and decreasing homocysteine levels.Acknowledgements:This research was supported by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program ’(Z.S.); by the European Union grant GINOP-2.3.2-15-2016-00015 (Z.S.) and by the WI188341 investigator-initiated research (IIR) grant obtained from Pfizer US (Z.S.).Disclosure of Interests:Boglárka Soós: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Monika Czókolyová: None declared, Edit Végh: None declared, Szilvia Szamosi Speakers bureau: Roche, Zsófia Pethö: None declared, Katalin Gulyás: None declared, György Kerekes: None declared, Éva Szekanecz: None declared, Sándor Szántó Speakers bureau: Abbvie, MSD, Novartis, Consultant of: Abbvie, Novartis, Gabriella Szücs Speakers bureau: Actelion, Roche, Sager, Boehringer, Consultant of: Boehringer, Actelion, Sager, Uwe Christians: None declared, Jelena Klawitter: None declared, Tamas Seres: None declared, Zoltán Szekanecz Speakers bureau: Pfizer, Abbvie, Roche, Lilly, Novartis, Boehringer, Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: Pfizer

Emerging data indicate that germline mutations in transcription factors involved in hematopoiesis can lead to a cascade of downstream molecular alterations that modify the function of megakaryocytes (MK) and platelets. Our group and others have found that mutations in ETV6 lead to mild thrombocytopenia with a bleeding diathesis, red cell macrocytosis, and predisposition to lymphoblastic leukemia. The mechanisms responsible for thrombocytopenia and propensity for bleeding in patients with ETV6 mutations are unknown. We described families with missense mutations in the central domain (p.Pro214Leu) and the ETS DNA binding domain (p.Arg418Gly) of ETV6 that result in aberrant cellular localization of ETV6, decreased transcriptional repression, and impaired MK maturation. Deep sequencing of the platelet transcriptome revealed significant differences in mRNA expression levels between patients with the ETV6 p.Pro214Leu mutation and non-affected family members, indicating that ETV6 is critically involved in defining the molecular phenotype and function of platelets. We hypothesize that normal regulation and function of ETV6 is essential for the transcriptional machinery that controls megakaryocyte differentiation and formation of platelets that function normally under homeostatic conditions. We have successfully generated a CRISPR-Cas9 model to edit the genome of ETV6-expressing iPSC derived megakaryocyte cell line (imMKCL) to characterize the role of wild-type ETV6 in megakaryocyte development and elucidate the molecular mechanism driving mutant ETV6 mislocalization, transcriptional dysregulation, and subsequent dysmegakaryopoiesis and thrombocytopenia. In this imMKCL model, we have genetically engineered the cells to express wild-type, P214L, and the DNA binding domain mutations R418G and R369Q ETV6 fused to HALOtag, a reporter protein that can react with ligands carrying a variety of functionalities, including fluorescent labels, affinity handles, and attachment to solid phase, making this novel reporter conducive to immunofluorescence imaging, biochemical pulldown, and ChIPSeq. This system allows us to express wild type and mutant forms of ETV6 in appropriate allele ratios in imMKCL cells and various hematopoietic-relevant cell lines. Using this approach, we detected nuclear localization of wild-type ETV6 and altered cytoplasmic localization of both P214L and R418G ETV6 mutants. We have also demonstrated dimerization between both wild-type and mutant ETV6 in this cell model. Importantly, we have used HALOtag protein immunoprecipitation to demonstrate ETV6 binding to FLI1, another ETS family member and key transcriptional regulator of megakaryocyte development, suggesting that ETV6 and FLI1 cooperate to regulate megakaryopoiesis under homeostatic conditions. Altogether, these data suggest that mutant ETV6 functions as a dominant negative, sequestering wild type ETV6 in the cytoplasm, de-regulating key transcriptional targets for homeostatic megakaryocyte development. Ongoing studies will define the full repertoire of protein interactions and transcriptional targets of wild-type and mutant ETV6. Discoveries from this novel tool will further advance our understanding of normal megakaryocyte and platelet biology, and will provide potential therapeutic targets for disorders of platelet number and function to optimize the clinical approach to these patients. Disclosures Callaghan: Bayer: Consultancy, Speakers Bureau; Alnylum: Equity Ownership; Biomarin, Bioverativ, Grifols, Kedrion, Pfizer, Roche/Genentech, Shire, and Spark Therapeutics: Consultancy; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Global Blood Therapeutics: Consultancy; Novonordisk: Consultancy, Speakers Bureau; Octapharma: Consultancy; Pfizer: Research Funding; Roche: Research Funding; Shire/Takeda: Speakers Bureau; Roche/Genentech: Speakers Bureau.

Background:Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with osteoporosis. There have been very few data on the use of peripheral quantitative computed tomography (QCT) in anti-TNF-treated patients.Objectives:We wished to assess volumetric bone mineral density (BMD) by forearm QCT in conjunction with dual-energy X-ray absorptiometry (DXA) and bone biomarkers in RA and AS.Methods:Forty RA and AS patients treated with etanercept (ETN) or certolizumab pegol (CZP) were included in a 12-month follow-up study. Peripheral QCT and DXA BMD were determined. Bone biomarkers, such as PTH, osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin, DKK-1 and cathepsin K (CATHK) were assessed by ELISA.Results:There was no further bone loss during anti-TNF treatment. Volumetric and areal BMD showed significant correlations with each other (p<0.05). Total QCT BMD after 12 months was inversely determined by disease activity at baseline in the full cohort (p=0.030). Cortical BMD was negatively determined by baseline disease activity (p=0.005) and CATHK (p=0.025). In RA, VITD-0 determined QTRABBMD-12 (p=0.005). In the full cohort, the one-year change in QTRABBMD was related to TNF inhibition together with higher VITD-0 (p=0.031). Therapy and lower CATHK determined QCORTBMD changes (p=0.006). In RA, treatment together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment together with RANKL-0 (p<0.05) determined QCT BMD changes.Conclusion:QCT confirmed that biologics may attenuate bone loss. Disease activity, CATHK, RANKL and VITD may predict the effects of anti-TNF treatment on volumetric BMD changes. There may be differences between RA and AS in this respect.Acknowledgements:This research was supported by Hungarian National Scientific Research Fund (OTKA) grant No. K 105073 (H.P.B. and Z.S.); by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program ’(Z.S.); by the European Union grant GINOP-2.3.2-15-2016-00050 (Z.S.); and by the Pfizer Investigator Initiated Research Grants no. WS1695414 and WS1695450 (Z.S.).Disclosure of Interests:Balázs Juhász: None declared, Katalin Gulyás: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Anita Pusztai: None declared, Agnes Szentpetery: None declared, Zsófia Pethö: None declared, Nóra Bodnár: None declared, Attila Hamar: None declared, Levente Bodoki: None declared, Harjit Pal Bhattoa: None declared, Éva Szekanecz: None declared, Katalin Hodosi: None declared, Andrea Domjan: None declared, Szilvia Szamosi Speakers bureau: Roche, Csaba Horváth: None declared, Sándor Szántó Speakers bureau: Abbvie, MSD, Novartis, Consultant of: Abbvie, Novartis, Gabriella Szücs Speakers bureau: Roche, Boehringer, Actelion, Sager, Consultant of: Actelion, Boehringer, Hennie Raterman: None declared, WIllem Lems Speakers bureau: Pfizer, Amgen, Lilly, UCB, Galapagos, Consultant of: Pfizer, Amgen, Lilly, UCB, Galapagos, Oliver FitzGerald Speakers bureau: AbbVie, Janssen, Pfizer, Consultant of: BMS, Celgene, Eli Lilly, Janssen, Pfizer, Grant/research support from: AbbVie, BMS, Eli Lilly, Novartis, Pfizer, Zoltán Szekanecz Speakers bureau: Pfizer, Roche, Abbvie, Novartis, Lilly, Sanofi, Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: Pfizer, UCB.

e14074 Background: Accurate and comprehensive interpretation of genomic variants has become a bottleneck in clinical sequencing applications due to the accelerated implementation of precision oncology and the rapid growth of relevant biomedical findings. We therefore are motivated to build Ephesus, a framework enabling curation of clinical evidence for biomarkers in somatic cancers. Currently Ephesus is the primary content source for Roche NAVIFY Mutation Profiler (NMP). Methods: Ephesus’ data model ensures adherence to best practice in clinical genomic content curation. Variant classification followed the AMP guidelines for somatic variant interpretation. Approvals and recommendations from regulatory agencies and organizations (FDA, NCCN, etc.) are applied on a regional basis. The data model is mapped to a set of PostgreSQL relational tables. Strategies such as data normalization according to standard ontologies, a submit-review-approval workflow with change logs, and biologically relevant datatype constraints are adopted to enforce data integrity. Ephesus is deployed as a web application, of which the UI allows users to conduct edits, filtering, sorting and bulk operations on entities by attributes. To maximize curation efficiency, a number of inference rules are applied before the content is ingested into NMP. Results: Currently Ephesus is developed to guide data collection, browsing and summarizing related to these primary entities: Biomarkers, Evidence items, Genes, Variants, Variant groups, and Drugs. The content exported on 2020/01/27 contains > 170K biomarker profiles (including combinations), in the context of 13 major cancer types. To evaluate the clinical reporting value of the curated knowledge, more than 60k real clinical cancer patient samples from the AACR GENIE project were queried against Ephesus. We compared the results to the latest content from several major knowledgebases. We see that the performance of Ephesus/NMP excels the others. Conclusions: We have developed Ephesus, a practical content curation framework which provides a highly structured and user-friendly environment for clinically relevant somatic biomarkers. The framework improved the productivity and quality of the manual curation, met clinical interpretation scope and complexity, and assures data integrity and auditability. [Table: see text]

Background:Pneumococcal vaccination is recommended in patients with RA who are receiving conventional synthetic/biologic DMARDs.1 Upadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor engineered to have a greater selectivity for JAK1 versus JAK2, JAK3, and tyrosine kinase 2, and is approved for the treatment of RA.Objectives:The aim of this analysis was to assess the impact of long-term treatment with UPA + background MTX on immunologic responses to Prevnar 13® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]; PCV13) in patients with RA enrolled in the ongoing Phase 2 open-label extension study BALANCE-EXTEND.Methods:Patients from BALANCE-EXTEND receiving PCV13 vaccination were required to be on UPA 15 mg once daily (QD) or 30 mg QD and background MTX for ≥4 weeks prior to, and after, PCV13 vaccination; MTX was not interrupted prior to vaccination. Vaccination antibody titers were collected pre-vaccination (Week 0) and post-vaccination (Weeks 4 and 12). The primary variable was the proportion of patients with satisfactory humoral response to PCV13 (≥2-fold increase in antibody concentration from pre-vaccination [Week 0] in ≥6/12 pneumococcal antigens [1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F]) at 4 weeks post-vaccination.Results:Of 111 patients (UPA 15 mg, n=87; UPA 30 mg, n=24), 86% were female, most (98%) were white, and mean (standard deviation) age was 58.4 (12.0) years. Prior to vaccination, patients had a median (range) duration of RA of 9.3 (3.4–35.0) years and had been receiving UPA for a median (range) of 3.9 (3.0–4.9) years. All but 3 patients were taking concomitant MTX, and 44.1% were taking a CS (median daily dose, 5.0 mg). All 111 patients received PCV13, none discontinued UPA during the first 4 weeks, and blood samples were available from 83/23 and 79/22 patients in the UPA 15/30 mg groups at Weeks 4 and 12, respectively. At 4 weeks, satisfactory humoral response to PCV13 occurred in 67.5% (95% confidence interval [CI]: 57.4–77.5) and 56.5% (95% CI: 36.3–76.8) of patients receiving UPA 15 and 30 mg, respectively. At 12 weeks, satisfactory humoral response to PCV13 occurred in 64.6% (95% CI: 54.0–75.1) and 54.5% (95% CI: 33.7–75.4) of patients receiving UPA 15 and 30 mg, respectively (Figure 1). There was no clear difference in response between patients receiving and not receiving concomitant CS. Within 30 days post-vaccination, 2 adverse events (AEs) were considered as possibly related to UPA (1 case of diverticulitis, UPA 15 mg; 1 case of anemia, UPA 30 mg) and no serious AEs were reported (Table 1). Two patients experienced pyrexia and 1 subject each experienced vaccination-site pain and headache within 1 day post-vaccination (all in UPA 15 mg group).Table 1.Safety through 30 days post-PVC13 vaccination in UPA-treated patientsEvent, n (%)UPA 15 mg QD (n=87)UPA 30 mg QD (n=24)Any AE15 (17.2)3 (12.5)Serious AE00AE leading to discontinuation of study drug00AE with reasonable possibility of being related to UPAa1 (1.1)b1 (4.2)cDeath00aAs assessed by the investigator. bDiverticulitis. cAnemia.AE, adverse event; PVC13, Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]; QD, once daily; UPA, upadacitinib.Conclusion:Satisfactory humoral response to PCV13 at 4 weeks occurred in ~two-thirds of patients with RA receiving long-term treatment with UPA 15 mg QD + background MTX. This is broadly consistent with pneumococcal vaccine humoral responses observed in patients with RA treated with other JAK inhibitors, biologics, or placebo.2–4References:[1]Singh JA, et al. Arthritis Care Res 2016;68:1–25.[2]Winthrop KL, et al. Arthritis Res Ther 2019;21:102.[3]Bingham CO, et al. Ann Rheum Dis 2015;74:818–22.[4]Winthrop KL, et al. Ann Rheum Dis 2016;75:687–95.Acknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing assistance was provided by Frances Smith, PhD, of 2 the Nth, which was funded by AbbVie.Disclosure of Interests:Kevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB., Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB., Juan Ignacio Vargas Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB, Edit Drescher: None declared, CONRADO GARCIA GARCIA: None declared, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie, Jeffrey Enejosa Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Alan Kivitz Shareholder of: Amgen, Novartis, Gilead, GlaxoSmithKline, Pfizer Inc., and Sanofi, Speakers bureau: AbbVie, Celgene, Eli Lilly, Flexion, Genzyme, Horizon, Merck, Novartis, UCB, Pfizer Inc., Regeneron, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Genzyme, Gilead, Janssen, Pfizer Inc., Regeneron, Sanofi, SUN Pharma Advanced Research, and UCB

Background:Depression is present in up to half of patients with Rheumatoid Arthritis (RA). The association between this mood disorder and disease activity scores, including DAS28, SDAI and CDAI, has previously been described by various authors.Objectives:The aim of our study was assessed the effect of depression on the components of different disease activity scores.Methods:We performed a cross-sectional study of consecutive adults with RA, according to ACR/EULAR 2010 criteria. Sociodemographic data, comorbidities and current treatment were recorded. Disease activity was evaluated using DAS28-ESR, DAS28-CRP, SDAI and CDAI. Depression was assessed using PHQ-9 questionnaire. The PHQ-9 values were categorized in 4 groups as follows: 5 to 9, 10 to 14, 15 to 19, 20 or greater, represents mild, moderate, moderate/severe, and severe depression, respectively. A cutoff value of 10 or greater was set to define major depression. Statistical analysis: Student´s T, ANOVA and Chi2 tests. Multiple logistic regression.Results:Two hundred fifty eight patients were included, with a median (m) disease duration of 9 years (IQR 3.6-16.7). The m PHQ-9 score was 6 (IQR 2-12.3) and the prevalence of major depression was 33.7%. Patients with major depression had more tender and swollen joint count (TJC and SJC) (mean 4.9±4.3 vs 2.3±3.7, p<0.0001 and 2.9±3.3 vs 1.7±3.4, p=0.009), more pain (VAS [cm] mean 5.6±2.7 vs 3.3±2.6, p<0.0001), higher patient and physician global assessment (PGA and PhGA) (VAS [cm] mean 5.4±2.9 vs 3.1±2.5, p<0.0001 and 4.4±2.7 vs 2.4±2.4, p<0.0001) and CRP (mean 1.7±3.3 vs 0.7±1.1 mg/dl, p=0.01). ESR values were higher in the group with major depression, but the difference did not reach significance. Disease activity was higher in the depression group by all scores: DAS28-ESR (mean 4.3±1.4 vs 3.3±1.3, p<0.0001), DAS28-CRP (mean 3.9±1.4 vs 2.8±1.7, p<0.0001), SDAI (mean 19.2±12.7 vs 10.3±10.1, p<0.0001) and CDAI (mean 17.6±10.9 vs 9.6±9.9, p<0.0001). While 41 (15.9%) patients had high disease activity according to DAS28-ESR, only 34 (13.2%) had SDAI>26.In the multivariate analysis, evaluating the association of major depression with the different components of DAS28-ESR, DAS28-CRP, SDAI and CDAI, we observed that the presence of this mood disorder remained significantly associated with higher PGA in all the scores. In addition, a significant association was seen with higher TJC in both DAS28 scores.Conclusion:Patients with major depression had higher disease activity. It´s presence has a significantly association with the subjective items of the disease activity scores, particularly PGA. CRP value was the only objective component associated with depression.Disclosure of Interests:Carolina Ayelen Isnardi Speakers bureau: Bristol Myers Squibb, Janssen, Grant/research support from: Pfizer, Emilce Edith Schneeberger Speakers bureau: Abbvie, Amgen, Bristol Myers Squibb, Janssen, Eli Lilly, Boehringer Ingelheim, Pfizer, Genzyme, Grant/research support from: Pfizer, Dafne Capelusnik Speakers bureau: Bristol Myers Squibb, Grant/research support from: Pfizer, Marcela Bazzarelli: None declared, Laura Barloco: None declared, Eliana Soledad Blanco: None declared, Alejandro Benitez Speakers bureau: Abbvie, Novartis, Amgen, Federico Benavidez: None declared, SANTIAGO SCARAFIA: None declared, María Alicia Lazaro Speakers bureau: Abbvie, Rodolfo Perez Alamino Speakers bureau: Pfizer, Abbvie, Amgen, Bristol-Myers-Squibb, Lilly, Janssen, Novartis, Federico Colombres: None declared, María Paula Kohan: None declared, Julia Sosa: None declared, Luciana Gonzalez Lucero: None declared, Ana Lucía Barbaglia: None declared, Hernan Maldonado Ficco Speakers bureau: Pfizer, Abbvie, Jansen, Novartis, Bago, Bristol, Eli Lilly., Consultant of: Pfizer, Abbvie, Novartis, Jansen, Bago, Eli Lilly., Gustavo Citera Speakers bureau: Abbvie, Bristol-Myers-Squibb, Lilly, Jansen, Gema, Pfizer, Roche, Grant/research support from: Pfizer

Background:Cardiovascular (CV) disease and osteoporosis (OP) have become increasing challenges in the ageing population, even more in patients with inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and spondyloarthropathies. Both RA and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss, accelerated atherosclerosis, increased CV morbidity and mortality.Objectives:Bone and vascular biomarkers and parameters along with the effect of one-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS.Methods:Fifty-three patients including 36 RA patients treated with etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were assessed by ELISA. Bone density was assessed by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and pulse-wave velocity (PWV) were assessed by ultrasound. The effects of vascular markers on bone and bone effects on vasculature undergone statistical analysis.Results:Serum levels of vascular endothelial growth factor (VEGF), PDGF-BB, angiopoietin 2 (Ang2) and cathepsin K (CathK) decreased, procollagen type 1 N-propeptide (P1NP) and sclerostin (SOST) levels increased, soluble receptor activator nuclear kappa B ligand (sRANKL) and osteoprotegerin (OPG) levels showed no differences. When bone and vascular markers were correlated with each other, at baseline, OPG correlated with Ang2 and adiponectin. SOST correlated positively with ccIMT. DXA L2-4 BMD, DXA L1 BMD and DXA femoral neck (FN) BMD correlated with FMD and CRP. QCT trabecular BMD correlated with ccIMT and PON1. According to the univariate analysis, FMD correlated with OPG, ccIMT correlated with SOST and QCT trabecular BMD. Ang1, Ang2 and PDGF-BB showed correlation with Dickkopf-1 (DKK1). Ang2 also correlated with OPG. As suggested by the multivariate analysis, OPG determined FMD; DKK1 was an independent predictor of Ang1, Ang2 and PDGF-BB. OPG was a predictor of Ang2.Conclusion:In our study of anti-TNF treated RA and AS patients, vascular and bone parameters showed numerous correlations. The therapy was clinically effective, it halted further bone loss over 1 year and reduced the production of angiogenic markers.Acknowledgments:This research was supported by an investigator-initiated research grant from Pfizer.Disclosure of Interests:Monika Czókolyová: None declared, Katalin Gulyás: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Zsófia Pethö: None declared, Szilvia Szamosi: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Emese Balogh: None declared, Nóra Bodnár: None declared, Levente Bodoki: None declared, Agnes Szentpetery: None declared, Harjit Pal Bhattoa: None declared, György Kerekes: None declared, Katalin Hodosi: None declared, Andrea Domjan: None declared, Sándor Szántó: None declared, Gabriella Szücs: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen

Background:Oral JAK inhibitor, tofacitinib appeared as a new therapeutic option, beside biological therapies, which has already proven its safety and effectivity in RA, but we lack of knowledge how it affects density of bone structures and bone turnover markers.Objectives:The aim of this study was to assess the effects of one-year tofacitinib therapy on bone metabolism in patients with RA.Methods:Altogether 30 RA patients with active disease were recruited and treated with tofacitinib in this 12-months follow-up study. Mean age of patients were 52.8±10.0 years, duration of rheumatoid arthritis were 7.7±5.0 years. Half of the patients haven’t received biological treatment prior tofacitinib therapy, other half of the patients switched to tofacitinib therapy after completing washout. 15 patients received 2x5mg and 15 patients received 2x10mg tofacitinib daily for 12 months. On both arms 2-2 patients have discontinued treatment and excluded from the study. Assessments were performed at baseline, month 6 and 12. Levels of CRP and IgM rheumatoid factor (RF) antibodies were measured by quantitaive nephelometry and levels of anti-CCP, sclerostin, osteocalcin (OC), P1NP were assesed by ELISA. Bone density was assesed by DXA (dual-energy X-ray absorptiometry, Lunar) and pQCT imaging techniques. Levels of DKK-1, OPG, RANKL were measured by multiplex microbead immunoassay (BioLegend LEGENDplex). In addition, disease activity (DAS28), age and disease duration were also measured. Correlations were determined by Spearman’s analysis. Univariate and multiple regression analysis using the stepwise method was applied to investigate independent associations between DXA measurements (dependent variables) and laboratory parameters (independent variables).Results:Tofacitinib significantly reduced DAS28 (p<0.001) and HAQ values (p=0.001), also level of CRP (p<0.001) and We (p=0.014). With respect to bone biomarkers we have experienced significant increase in levels of OC (p=0.013), OPG (p=0.006), sclerostin (p=0.026) and vitamin-D (p=0.017) at month 6, also in levels of OPG and vitamin-D (p=0.004, p=0.003) at month 12. We have found decrease in levels of CTX at month 6 (p=0.009) and 12 (p=0.003). When we examined the groups separately, we’ve found significant increase in levels of P1NP (p=0.027, p=0.005), OPG (p=0.005, p=0.002) and vitamin-D (p=0.001, p=0.004) at month 6 and 12, also in OC at month 6 (p=0.027) in Group A (2x5mg). In Group B (2x10mg) we’ve experienced a significant decrease in levels of phosphate and CTX at month 6 and 12 (p=0.012, p=0.021, and p=0.005, p=0.007).Conclusion:One year tofacitinib treatment effectively stabilized bone density in patients with rheumatoid arthritis, and led to the increase of bone turnover markers, which is beneficial for ossification in long term.Acknowledgments:This research was supported by an investigator-initiated research grant from Pfizer.Disclosure of Interests:Attila Hamar: None declared, Anita Pusztai: None declared, Edit Végh: None declared, Ágnes Horváth: None declared, Szilvia Szamosi: None declared, Zsófia Pethö: None declared, Sándor Szántó: None declared, Gabriella Szücs: None declared, Harjit Pal Bhattoa: None declared, Gábor Tajti: None declared, György Panyi: None declared, Katalin Hodosi: None declared, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen

Vor 20 Jahren, am 29. Januar 1989, verstarb Edith Rothe. Vom Herbst 1945 bis in den Frühsommer 1951 leitete sie die Leipziger Stadtbibliothek. Als sie 1945 nach Leipzig kam, lag die Stadtbibliothek in Trümmern, die Bücher waren verbrannt oder ausgelagert. Innerhalb von fünf Jahren schaffte sie es, gemeinsam mit ihren Mitarbeitern, eine neue Stadtbibliothek aufzubauen. Doch aus politischen Gründen musste sie 1951 ihre Wirkungsstätte verlassen.