tbuckley/cabot-search huggingface dataset:
AB0919 Validation of proteomic biomarkers observed in monozygotic twins confirms two proteins associated with psoriatic disease
Authors: E. Generali, N. Isailovic, A. Ceribelli, F. Sacrini, M. De Santis, M. Meroni, G.M. Guidelli, M. Caprioli, A. Costanzo, C. Selmi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Skin psoriasis affects 3% of the general population and as much as 20%–40% of patients will develop psoriatic arthritis (PsA), with the two conditions representing a clinical and immunological continuum within a prototype for chronic inflammation. Different from most rheumatic diseases, no serum autoantibody is associated with PsA, and there are currently no biomarkers for an early diagnosis and prediction of PsA onset in psoriasis, frequently causing a delayed diagnosis. Monozygotic twins discordant for psoriasis/PsA represent a unique setting to investigate the influence of environmental and stochastic factors on disease phenotype. Through a high-throughput proteomic analysis (SomaLogic) we have previously identified a set of 13 proteins differentially expressed in the serum of monozygotic twins discordant for psoriatic disease. <h3>Objectives</h3> To validate serum proteomic biomarkers of psoriatic disease using commercially available ELISA in monozygotic twins and in unrelated patients with psoriasis or PsA. <h3>Methods</h3> Our study included sera from our cohort of monozygotic twins previously described and from 70 unrelated patients with psoriatic disease (psoriasis without PsA 34%–49%, PsA with/without psoriasis 36%–51%; women 46%, median age 52 years, interquartile range 41–59) followed at Humanitas Research Hospital, and 25 healthy subjects (52% women, median age 52 years, IQR 44–62). Candidate serum proteomic biomarkers obtained by SomaLogic analysis were validated using commercially available ELISA kits and proteins are herein anonymized due to a pending patent request. <h3>Results</h3> We found a significant correlation between SomaLogic results in monozygotic twins and ELISA results in unrelated psoriatic cases in the serum levels of 2 proteins (figure 1), which are involved in inflammatory and immune response, and one has been previously reported in psoriatic plaques. Four proteins showed a significantly different expression between psoriasis and PsA versus controls, in particular two proteins have a potential role in disease pathogenesis, as protein #1 acts as cell-surface receptor and regulates differentiation, proliferation and survival of dendritic cells, while protein #2 is involved in regulation of UV radiation-induced apoptosis and protein folding. <h3>Conclusions</h3> Two serum proteomic biomarkers, previously identified in a cohort of monozygotic twins discordant for psoriatic disease, can discriminate psoriatic disease, thus representing potential biomarkers of disease and possibly playing a pathogenetic role in disease. <h3>Disclosure of Interest</h3> None declared
Authors’ reply to Sugiyama
Authors: Fernando Rivadeneira, Katerina Trajanoska, John Morris, J Brent Richards
Journal: BMJ (2019)

A large body of data from randomised clinical trials and large meta-analyses has shown no clear evidence for a beneficial effect of vitamin D on bone mineral density or fracture risk.1 Notably, recent studies have shown that high vitamin D concentrations (above the physiological requirements) can have a deleterious effect on bone health.23 Furthermore, …
OP0238 Association between age at diagnosis and clinical presentation and outcomes of anca-associated vasculitis. analysis from the dcvas study
Authors: S Monti, A. Craven, C. Klersy, C. Montecucco, R. Caporali, R. Watts, P.A. Merkel, R. Luqmani
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> ANCA-associated vasculitis (AAV) can affect all age groups. Nevertheless, the differences in disease presentation and outcome between younger and elderly-onset patients are still incompletely understood.<sup><sup>2</sup></sup> <h3>Objectives</h3> To identify distinguishing characteristics of clinical presentations, short-term outcomes and accumulated damage for AAV, based on age of disease onset. <h3>Methods</h3> We included patients with a final diagnosis of AAV: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA) enrolled in The Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study through May 2017. We divided the population according to age at diagnosis:&lt;65 years old (group A) or ≥65 (group B). <h3>Results</h3> We included 1338 patients. 66% had a disease onset &lt;65 years of age (male:50%; mean age 48.4±12.6 years); 34% had an elderly-onset (male: 46%; mean age 73.6±6). The diagnoses of GPA and EGPA were more frequent in group A (73% and 74% of patients, respectively) compared to MPA (56%), p&lt;0.001 for comparisons within each diagnostic group. P-ANCA/anti-MPO positivity was more frequent in group B (48% vs 27%, p=0.001); c-ANCA/PR3 predominated in group A (48% vs 35%; p&lt;0.001). The clinical presentation at onset significantly differed between the two groups. Patients from group A had higher rates of ocular, cutaneous, and musculoskeletal involvement compared to patients in group B who experienced more systemic, renal, cardiovascular, and neurological manifestations (figure 1). Pulmonary and gastrointestinal manifestations were equally distributed between the two age groups. Vasculitis Damage Index (VDI) was significantly higher in patients from group B, with 12% of patients with a 6 months VDI score ≥5, compared to 7% in group A; p=0.01. There were 13 (1.5%) deaths amongst patients belonging to group A compared to 22 (4.8%) in group B, HR 3.44 (1.65–7.18); p=0.001. <h3>Conclusions</h3> Patients with AAV with elderly-onset disease display a different pattern of organ-involvement and an increased risk of significant damage and mortality compared to younger patients. A better understanding of the influence of age of onset on the clinical course of AAV could improve diagnostic and classification criteria and has implications on their pattern of presentation and subsequent clinical course. <h3>References</h3> [1] Watts RA, et al. Epidemiology of systemic vasculitis. Arthritis Rheum2000;43:414–19. [2] Chen M, et al. Antineutrophil cytoplasmic autoantibody-associated vasculitis in older patients. Medicine2008;87:203–9. <h3>Disclosure of Interest</h3> None declared
AB1412-HPR Is diffuse alveolar haemorrhage in anca- associated vasculitis predictive of poor prognosis?
Authors: L. Garcia, C. Pena, R. Aguila Maldonado, A.C Costi, A. Testi, V. Nagua, M.A. Garcia
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Diffuse alveolar haemorrhage (DAH) is a serious complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Detailed characteristics of patients with AAV and associated DAH have been limited to case reports and a few case series, due to the rarity of the condition(.<sup>1</sup> Prompt diagnosis is required as early treatment is crucial. <h3>Objectives</h3> To compare clinical manifestations, laboratory and inmunological values, morbidity and mortality in patients with ANCA-associated vasculitis (AAV) with and without Diffuse Alveolar haemorrhage (DAH) <h3>Methods</h3> Retrospective cohort study. Data from the medical records of patients over the age of 18 were evaluated between the years 2000–2017. Ninety patients with diagnosis of AAV who met the criteria of ACR 1990 Classification or Chapel Hill Concensus Conference 2012 were included. DAH was diagnosed based on minor or major hemoptysis and/or respiratory insufficiency together with at least 1 positive result on x-ray and/or computed tomography scan. The sample was divided in two groups: with DAH (group 1) and without DAH (group 2) along the disease. We compared demographic data, Birmingham Vasculitis Activity Score (BVAS) and Five Factor Score (FFS) at the onset of the desease, hemogram, creatinine and ANCA antibodies by inmunofluoresence and/or ELISA, clinical manifestations as renal, neurological, mucocutaneous, articular, cardiological, oftalmological and ear, nose and throat (ENT) damage and mortality between groups. Chi-square or Fisher's exact test was used for dichotomous variables as appropriate. P-value&lt;0.05 was considered statistically significant. Logistic regression analysis was used to identify predictors of survival. <h3>Results</h3> Group 1 included 24 patients (66% male, mean age at onset of the disease 54 years). Most frequent type of vasculitis was Granulomatosis with polyangeitis (GPA) 54%. Mean BVAS 21 points and FFS 1 point. Group 2 included 66 patients: 36% male, mean age of the desease 52 years, GPA 45%, BVAS was 17 points and FFS de 0 points. Table 1 shows demographic, clinical data and mortality of each group. Logistic regression analysis showed statistically significant difference between DAH and male sex (p: 0.017 OR 6.08 CI 95% 1.37–26.92). <h3>Conclusions</h3> DAH was associated with increased morbidity but not modified the mortality in this group of patients. The results seem to be agree on the Five Factor Score<sup>2</sup> that does not include DAH within parameters. <h3>References</h3> [1] West, S, et al. Diffuse Alveolar Haemorrhage in ANCA-associated Vasculitis. Intern Med52: 5–13, 2013. [2] Guillevin, L, et al. The Five- Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the FVSG cohort. Medicine (Baltimore)2011; 90: 19–27. <h3>Disclosure of Interest</h3> None declared
SAT0541 Incidence of large vessel gca in northern italy during a 12-year period (2005–2016)
Authors: P. Macchioni, L. Boiardi, G. Restuccia, F. Muratore, P. Mancuso, M. Catanoso, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> There are no studies regarding the incidence of large vessel GCA (LV GCA). <h3>Objectives</h3> To investigate the incidence of LVGCA in the Reggio Emilia Area from 2005 through to 2016. <h3>Methods</h3> All patients with incident large vessel GCA diagnosed between 1 January 2005 and 31 December 2016 and living in the Reggio Emilia area, were identified by capture and re-capture checking of computerised discharge diagnosis codes (ICD10) and using outpatients databases from rheumatology, internal medicine, surgery, pathology, imaging departments of Reggio Emilia Hospital as well as by examining the Reggio Emilia district database for rare diseases. To be included in the study, patients must satisfy the following 2 criteria: Age at disease onset ≥50 years; evidence of large-vessel vasculitis by angiography, MRA, CTA, PET/CT and/or ultrasonography. We included in the study also patients associating biopsy proven GCA with evidence of LVV. We also evaluated the incidence of biopsy proven GCA without LV in same time period. <h3>Results</h3> There were 93 incident cases of LV GCA (66 women, 71%) during the 12 year study period; Mean ±SD age at diagnosis was 72±9 years. Incidence per 1 00 000 persons aged ≥50 years was 3.78 (95% confidence interval [95% CI 3.01, 4.55]). In particular incidence was 1.60 in LV GCA with biopsy proven GCA and 2.18 in LV GCA not biopsy proven GCA (pts biopsy negative and pts in which the biopsy had not been performed). Incidence was significantly higher in women (4.89 [95% CI 3.69, 6.09] than in men (2.50 [95% CI 1.56, 3.45]) (p&lt;0.0006). The highest incidence in women was observed in the 70–79 years age group (7.72 [95% CI 4.89,11.58] while in men the peak of incidence was in the 80–89 age group (4.23 [95% CI 2.50,8.45]). A progressive increase in total incidence rates was observed during the 4 three years periods from 3.13 (2005–2007) to 4.85 (2014–2016). The incidence per 1 00 000 persons aged ≥50 years of GCA biopsy proven without LV during the 12 year study period was 4.48 [95% CI 2.22,9.45]. <h3>Conclusions</h3> The incidence of LV GCA in the Reggio Emilia area 100.000/aged &gt;50 was 3.78 and it was lower than that of patients with biopsy proven GCA without LV; the incidence of LV GCA was significantly higher in women and increased during the study period. <h3>Reference</h3> [1] Catanoso M, et al. Arthritis Care Res (Hoboken)2017Mar;69(3):430–438. <h3>Disclosure of Interest</h3> None declared
RNA sequencing data integration reveals an miRNA interactome of osteoarthritis cartilage
Authors: Rodrigo Coutinho de Almeida, Yolande F M Ramos, Ahmed Mahfouz, Wouter den Hollander, Nico Lakenberg, Evelyn Houtman, Marcella van Hoolwerff, H Eka D Suchiman, Alejandro Rodríguez Ruiz, P Eline Slagboom, Hailiang Mei, Szymon M Kiełbasa, Rob G H H Nelissen, Marcel Reinders, Ingrid Meulenbelt
Journal: Annals of the Rheumatic Diseases (2018)

Objective To uncover the microRNA (miRNA) interactome of the osteoarthritis (OA) pathophysiological process in the cartilage. Methods We performed RNA sequencing in 130 samples (n=35 and n=30 pairs for messenger RNA (mRNA) and miRNA, respectively) on macroscopically preserved and lesioned OA cartilage from the same patient and performed differential expression (DE) analysis of miRNA and mRNAs. To build an OA-specific miRNA interactome, a prioritisation scheme was applied based on inverse Pearson’s correlations and inverse DE of miRNAs and mRNAs. Subsequently, these were filtered by those present in predicted (TargetScan/microT-CDS) and/or experimentally validated (miRTarBase/TarBase) public databases. Pathway enrichment analysis was applied to elucidate OA-related pathways likely mediated by miRNA regulatory mechanisms. Results We found 142 miRNAs and 2387 mRNAs to be differentially expressed between lesioned and preserved OA articular cartilage. After applying prioritisation towards likely miRNA-mRNA targets, a regulatory network of 62 miRNAs targeting 238 mRNAs was created. Subsequent pathway enrichment analysis of these mRNAs (or genes) elucidated that genes within the ‘nervous system development’ are likely mediated by miRNA regulatory mechanisms (familywise error=8.4×10 −5 ). Herein NTF3 encodes neurotrophin-3, which controls survival and differentiation of neurons and which is closely related to the nerve growth factor. Conclusions By an integrated approach of miRNA and mRNA sequencing data of OA cartilage, an OA miRNA interactome and related pathways were elucidated. Our functional data demonstrated interacting levels at which miRNA affects expression of genes in the cartilage and exemplified the complexity of functionally validating a network of genes that may be targeted by multiple miRNAs.
SP0020 How digital tools can help to cross borders in international collaborations
Authors: V. Seyfert-Margolis
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> When people think of digital health, they generally think of health and wellness mobile apps, or wearable sensor devices like Fit Bit or the Apple Watch. But digital technologies are much more than that. Today's advanced digital health has evolved into software platforms that can connect and support patients, their families and connect them to their health systems, enabling outcomes research and management with direct input from networks of patients that can connect across geographical divides. And these systems enable communication between medical systems, enabling hubs and spokes of networked researchers and their patients that promote data capture, information sharing and enhanced communications to patients- by meeting them where they are. These new models are driving the ability to study interventions in real world contexts including patients' between visit activities and their engagement with multiple layers of the healthcare teams thereby promoting integrated research and care. With all of these capabilities, the question remains, "will the medical research community be ready to embrace it?" <h3>Disclosure of Interest</h3> None declared
Neutrophil extracellular traps in <i>ex vivo</i> lung perfusion perfusate predict the clinical outcome of lung transplant recipients
Authors: Lindsay Caldarone, Andrea Mariscal, Andrew Sage, Meraj Khan, Stephen Juvet, Tereza Martinu, Ricardo Zamel, Marcelo Cypel, Mingyao Liu, Nades Palaniyar, Shaf Keshavjee
Journal: European Respiratory Journal (2019)

<b>Neutrophil extracellular traps (NETs) are detectable in donor <i>ex vivo</i> lung perfusate, and higher levels of NETs in perfusate are associated with worse recipient outcomes after transplant</b>http://ow.ly/r4nM30nvZsK
Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO Group)
Authors: R. Garcia-Sanz, A. Sureda, F. de la Cruz, M. Canales, A.P. Gonzalez, J.L. Pinana, A. Rodriguez, A. Gutierrez, E. Domingo-Domenech, B. Sanchez-Gonzalez, G. Rodriguez, J. Lopez, M. Moreno, M.J. Rodriguez-Salazar, S. Jimenez-Cabrera, M.D. Caballero, C. Martinez
Journal: Annals of Oncology (2019)

In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT).
FRI0681 Four comorbidity indexes among patients with rheumatoid arthritis
Authors: Y. J. Huang, C. F. Kuo, J. S. Chen, S. F. Luo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Previous studies have reported an increased risk of multiple comorbidities in people with RA therefore it is necessary to systematically quantify the comorbidity burden of these patients.[1] The comorbidity index is a tool developed under this concept and has multiple clinical and research uses. <h3>Objectives:</h3> We compared four comorbidity indexes in patients with rheumatoid arthritis in Taiwan (Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index (ECI), Mutimorbidity index (MMI), Rheumatic Disease Comorbidity Index (RDCI)) <h3>Methods:</h3> All patients with rheumatoid arthritis diagnosed during 1998–2008 in Taiwan were identified using the Taiwan National Health Insurance Database and followed up to 31 Dec 2013. Score accumulation between periods during diagnosis (4 months before and after initial diagnosis) and before/after the diagnostic period was compared. Poisson regression was used to calculate incidence rate ratio. <h3>Results:</h3> Among 24767 patients with rheumatoid arthritis, median age at diagnosis is 51 years old and female is 79.2%. The mean score at diagnosis is 0.8 in CCI, 2.8 in ECI, 0.7 in MMI and 1.3 in RDCI. The annual percentage changes are 11.0%, 11.3%, 9.7% and 6.8%, respectively. The score of four comorbidity indexes increased with time after rheumatoid arthritis was diagnosed. The incidence rate ratios (IRR) for any increase in comorbidity score during versus before diagnostic period are higher than after versus before diagnostic period. (IRR 1.8 [CI 1.68 to 1.92] vs. 1.57 [CI 1.47 to 1.69] in CCI, IRR 2.77 [CI 2.67 to 2.87] vs. 2.44 [CI 2.36 to 2.53] in ECI, IRR 1.33 [CI 1.26 to 1.40] vs. 1.26 [CI 1.19 to 1.33] in MMI, IRR 1.47 [CI 1.41 to 1.54] vs. 1.31[CI 1.26 to 1.37] in RDCI) Table 1 Incidence rates (IR) per 1000 patient months and incidence rate ratios (IRR) for occurrence of any disease in comorbidity index before, during, and after diagnosis* in patients with incident rheumatoid arthritis, 2001–2008, Taiwan. <h3>Conclusions:</h3> Our study showed that comorbidities continue to accumulate after the initial diagnosis. The comorbidity tends to occur during diagnostic period in patients with rheumatoid arthritis. Different comorbidity indexes are all good at assessing comorbidity burden. Clinicians should screen different comorbidities, determine primary prevention and control disease activity to improve the functional status, quality of life and mortality of rheumatoid arthritis. <h3>Reference</h3> 1. Baillet A, et al. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheum Dis, 2016;75(6):965–73. <h3>Disclosure of Interest:</h3> None declared
A Proactive Approach Needed to Combat Rising STIs
Authors: Bridget M. Kuehn
Journal: JAMA (2019)

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Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of a Multicenter Study from the Grupo Español De Trasplante Hematopoyético (GETH)
Authors: Leyre Bento, Jose Maria Bastida, Irene García-Cadenas, Estefania García-Torres, Daniel Rivera, Anna Bosch, Carlos de Miguel, María Esther Martínez-Muñoz, Francesc Fernández-Avilés, Elisa Roldan, Anabelle Chinea, Lucrecia Yáñez, Teresa Zudaire, Carlos Pinho-Vaz, Ildefonso Espigado, Javier Lopez Jimenez, David Valcárcel, Rafael F Duarte, Rafael Cabrera, Antonio Gutiérrez, Carlos Solano, Antonia Sampol
Journal: Blood (2018)