tbuckley/cabot-search huggingface dataset:
OP0304 Multidisciplinary collaboration among young specialists: results of an ongoing international survey by young organisations
Authors: M. Kostine, A. Najm, J. Pauling, A.C. Ferreira, K. Stevens, E. Smith, I. Eguiluz Gracia, S. Ramiro, E. Nikiphorou, A. Molto, A. Alunno, P. Studenic, A. Sepriano, J. Rodríguez Carrio, C. Richez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Young clinicians and researchers frequently work alongside other medical specialists in order to share expertise, knowledge and skills. Multidisciplinary work is worthwhile but may be sometimes challenging. <h3>Objectives</h3> To describe current clinical and research collaboration among young specialists and to identify some perspectives to develop such collaborations. <h3>Methods</h3> An online survey was disseminated by email and social media (facebook and twitter) to members of the Emerging European League Against Rheumatism Network (EMEUNET), the Young Nephrologists’ Platform (YNP), the Paediatric Rheumatology European Society Emerging Rheumatologists and Researchers (PReS EMERGE), and the European Academy of Allergy and Clinical Immunology Junior Members (EAACI JM). <h3>Results</h3> Of 354 respondents from 40 countries, 60% were female, 23% were aged below 30 years and 67% 31–40 years. Young rheumatologists were the most represented (36%), followed by young nephrologists (24%), young paediatricians (18%), young allergologists (11%) then young internists (3%) and several other specialties (as clinical immunology, dermatology, pulmonology, orthopaedics). 60% were certified specialists, 34% in training and 6% were researchers without clinical work. Overall, the top 3 specialties for clinical collaboration in daily practice were radiology, cardiology and dermatology. Collaborations were reported frequently by phone and email, also by various combined clinics while common local multidisciplinary meetings were uncommon. Of note, 71% of respondents found collaboration with young colleagues easier than with senior specialists. Research collaboration usually started by knowing other specialists (73%) and/or by attending common meetings (39%). 96% would like to develop clinical research collaborations and 69% basic research collaborations. The majority of young specialists would be interested in online (84%) and/or 1–2 days (86%) common courses including cases discussion (80%) and training workshops (84%), as well as webinars recorded with several specialists on a specific disease (96%). Respondents were a bit less enthusiastic with developing collaboration through social media (facebook 61%, twitter 58%) but interested in common apps (71%). <h3>Conclusions</h3> This collaborative initiative highlighted wishes from young specialists for developing 1) regular local multidisciplinary meetings to discuss complex patients 2) clinical research collaboration with combined grants and 3) multidisciplinary online projects such as common courses, webinars and apps. <h3>Acknowledgements</h3> We thank all members of young organisations for their active participation. <h3>Disclosure of Interest</h3> None declared
Coronary Artery Calcium on Noncontrast Thoracic Computerized Tomography Scans and All-Cause Mortality
Authors: Matthew J. Budoff, Sharon M. Lutz, Gregory L. Kinney, Kendra A. Young, John E. Hokanson, R. Graham Barr, Robert Steiner, Hrudaya Nath, Carmen Lopez-Garcia, Lindsey M. Duca, Sina Rahmani, Kazuhiro Osawa, Elizabeth A. Regan, Dong Li, Richard Casaburi
Journal: Circulation (2018)
Anti-drug Antibody Responses Impair Prophylaxis Mediated by AAV-Delivered HIV-1 Broadly Neutralizing Antibodies
Authors: Matthew R. Gardner, Ina Fetzer, Lisa M. Kattenhorn, Meredith E. Davis-Gardner, Amber S. Zhou, Barnett Alfant, Jesse A. Weber, Hema R. Kondur, Jose M. Martinez-Navio, Sebastian P. Fuchs, Ronald C. Desrosiers, Guangping Gao, Jeffrey D. Lifson, Michael Farzan
Journal: Molecular Therapy (2019)

Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention of HIV-1 infection. The immunoglobulin G (IgG)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. However, the use of IgG1-Fc has been associated with the generation of anti-drug antibodies (ADAs) that correlate with loss of antibody expression. In contrast, we have shown that expression of the antibody-like molecule eCD4-Ig bearing a rhesus IgG2-Fc domain showed reduced immunogenicity and completely protected rhesus macaques from simian-HIV (SHIV)-AD8 challenges. To directly compare the performance of the IgG1-Fc and the IgG2-Fc domains in a prophylactic setting, we compared AAV1 expression of rhesus IgG1 and IgG2 forms of four anti-HIV bNAbs: 3BNC117, NIH45-46, 10-1074, and PGT121. Interestingly, IgG2-isotyped bNAbs elicited significantly lower ADA than their IgG1 counterparts. We also observed significant protection from two SHIV-AD8 challenges in macaques expressing IgG2-isotyped bNAbs, but not from those expressing IgG1. Our data suggest that monoclonal antibodies isotyped with IgG2-Fc domains are less immunogenic than their IgG1 counterparts, and they highlight ADAs as a key barrier to the use of AAV1-expressed bNAbs. Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention of HIV-1 infection. The immunoglobulin G (IgG)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. However, the use of IgG1-Fc has been associated with the generation of anti-drug antibodies (ADAs) that correlate with loss of antibody expression. In contrast, we have shown that expression of the antibody-like molecule eCD4-Ig bearing a rhesus IgG2-Fc domain showed reduced immunogenicity and completely protected rhesus macaques from simian-HIV (SHIV)-AD8 challenges. To directly compare the performance of the IgG1-Fc and the IgG2-Fc domains in a prophylactic setting, we compared AAV1 expression of rhesus IgG1 and IgG2 forms of four anti-HIV bNAbs: 3BNC117, NIH45-46, 10-1074, and PGT121. Interestingly, IgG2-isotyped bNAbs elicited significantly lower ADA than their IgG1 counterparts. We also observed significant protection from two SHIV-AD8 challenges in macaques expressing IgG2-isotyped bNAbs, but not from those expressing IgG1. Our data suggest that monoclonal antibodies isotyped with IgG2-Fc domains are less immunogenic than their IgG1 counterparts, and they highlight ADAs as a key barrier to the use of AAV1-expressed bNAbs.
THU0628 Differences in clinical manifestations of behcet’s syndrome by gender: cross-sectional analysis in a uk cohort
Authors: L. Chadwick, T. Blake, N.J. Goodson, D. Situnayake, R.J. Moots
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Geographical variations in genotype and phenotype of Behçet's syndrome (BS) are reported.<sup>1,2</sup> Previous meta-analysis of international cohorts has highlighted differences in clinical manifestations of BS by gender.<sup>3</sup> A comparison of BS clinical manifestations by gender has not been analysed previously in a large UK BS cohort. <h3>Objectives</h3> 1) To compare the clinical manifestations of BS in a UK cohort by gender and 2) to compare this to published international data. <h3>Methods</h3> A retrospective cross sectional analysis was performed using clinical databases at the Liverpool and Birmingham BS Centres of Excellence. Patients with a multi-disciplinary diagnosis of BS or International Study Group (ISG) diagnostic criteria were included. Clinical manifestations and HLA-B51 positivity were compared by gender. T-tests and chi-squared tests were used for continuous and categorical data respectively and a p value of 0.05 or less was considered statistically significant. <h3>Results</h3> 433 patients met inclusion criteria (140 males, 32.3%). Male patients were younger and had significantly higher rates of ocular and vascular involvement, papulopustular skin rash and HLA-B51 positivity. Female patients had significantly higher rates of genital aphthosis and arthralgia. <h3>Conclusions</h3> Similar to published international cohorts, male patients with BS in the UK have higher rates of ocular and venous involvement, papulopustular skin rash and HLA-B51 positivity and lower rates of genital aphthosis and arthralgia in comparison to female patients. However, the extent to which these differences are attributable to ethnicity is unclear. <h3>References</h3> [1] Leonardo NM, McNeil J. Behcet's Disease: Is There Geographical Variation? A Review Far from the Silk Road. Int J Rheumatol2015: 1–7. doi:10.1155/2015/945262 [2] Sibley C, Yazici Y, Tascilar K, Khan N, Bata Y, Yazici H, et al. Behçet syndrome manifestations and activity in the United States versus Turkey - a cross-sectional cohort comparison. J Rheumatol2014;41:137984. doi:10.3899/jrheum.131227 [3] Bonitsis NG, Nguyen LBL, LaValley MP, Papoutsis N, Altenburg A, et al. Gender-specific differences in Adamantiades-Behçet's disease manifestations: an analysis of the German registry and meta-analysis of data from the literature. Rheumatology (Oxford). 2015;54: 121–33. doi:10.1093/rheumatology/keu247 <h3>Disclosure of Interest</h3> None declared
Abstract 16465: A Lower Than Normal Aortic Diameter is a Prognostic Marker of Cardiac Events in Severe Dilated Cardiomyopathy
Authors: Misato Chimura, Tomohito Ohtani, Themis katsimichas, Kaoruko Sengoku, Tatsunori Taniguchi, Kenji Nakamura, Kei Nakamoto, Toshinari Ohnishi, Yasumasa Tsukamoto, Hidetaka Kioka, Yasushi Sakata
Journal: Circulation (2016)

Introduction: An aortic diameter below the lower normal limit is observed in some dilated cardiomyopathy (DCM) patients and its clinical meaning is unknown. Hypothesis: We hypothesized that smaller aortic diameter is associated with persisting severe LV dysfunction and can predict worse outcomes, such as the need for left ventricular assist device (LVAD) implantation or death in severe DCM patients. Methods: We enrolled 73 consecutive patients with DCM (age 43±13 years, 56 males, LV ejection fraction (EF) 19±7 %) who were hospitalized for severe heart failure (HF) (NYHA III or IV) in Osaka University Hospital. The aortic diameter was defined as the diameter of ascending aorta at the level of the pulmonary artery bifurcation measured by multiple detector computed tomography. A small aortic diameter (SA) was defined as a diameter below the lower normal limit adjusted for age, gender and body surface area based on previous report. LV characteristics were obtained by echocardiography. We followed the patients...
The Genomic Landscape of Mucinous Breast Cancer
Authors: Fresia Pareja, Ju Youn Lee, David N Brown, Salvatore Piscuoglio, Rodrigo Gularte-Mérida, Pier Selenica, Arnaud Da Cruz Paula, Sasi Arunachalam, Rahul Kumar, Felipe C Geyer, Catarina Silveira, Edaise M da Silva, Anqi Li, Caterina Marchiò, Charlotte K Y Ng, Odette Mariani, Laetitia Fuhrmann, Hannah Y Wen, Larry Norton, Anne Vincent-Salomon, Edi Brogi, Jorge S Reis-Filho, Britta Weigelt
Journal: JNCI Journal of the National Cancer Institute (2018)

Mucinous carcinoma of the breast (MCB) is a rare histologic form of estrogen receptor (ER)-positive/HER2-negative breast cancer (BC) characterized by tumor cells floating in lakes of mucin. We assessed the genomic landscape of 32 MCBs by whole-exome sequencing and/or RNA-sequencing. GATA3 (23.8%), KMT2C (19.0%), and MAP3K1 (14.3%) were the most frequently mutated genes in pure MCBs. In addition, two recurrent but not pathognomonic fusion genes, OAZ1-CSNK1G2 and RFC4-LPP, were detected in 3/31 (9.7%) and 2/31 (6.5%) samples, respectively. Compared with ER-positive/HER2-negative common forms of BC, MCBs displayed lower PIK3CA and TP53 mutation rates and fewer concurrent 1q gains and 16q losses. Clonal decomposition analysis of the mucinous and ductal components independently microdissected from five mixed MCBs revealed that they are clonally related and evolve following clonal selection or parallel evolution. Our findings indicate that MCB represents a genetically distinct ER-positive/HER2-negative form of BC.
OP0203 Safety and efficacy of intravenous administration of bone-marrow derived mesenchymal stromal cells in therapy refractory juvenile idiopathic arthritis patients, a phase ib/iia pilot-study
Authors: J.F. Swart, S. de Roock, R.J. Nievelstein, I. Slaper-Cortenbach, J.J. Boelens, N. Wulffraat
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To compare the total number of adverse events (AE's) before and after mesenchymal stromal cell (MSC) infusion in refractory JIA and to evaluate its effectiveness. <h3>Methods</h3> Single-centre Phase Ib/IIa, open label intervention study in JIA patients previously failing all biologicals registered for their diagnosis. Six patients will receive 2 million/kg intravenous infusions of allogeneic bone-marrow derived MSC. In case of ACR-Ped30-response but subsequent loss of response one and maximal two repeated infusions are allowed. <h3>Results</h3> Six JIA patients with 9.2 years median disease duration, still active arthritis and damage were included. All had failed methotrexate, corticosteroids and median 5 different biologicals. MSC were administered twice in 3 patients. No acute infusion reactions were observed and a lower post-treatment than pre-treatment incidence in AE's was found. The one sJIA patient had again an evolving macrophage activation syndrome, 9 weeks after tocilizumab discontinuation and 7 weeks post- MSC infusion. Eight weeks after one MSC infusion, 4 patients showed less active joints, 5 patients improved in many clinical parameters and inflammatory parameters decreased in 3/4. After 1 year, we found significantly lower active joint counts, improved well-being scores, normalised median ESR- and CRP-levels. Inactive disease was reached by 3 patients at 1 year. <h3>Conclusions</h3> MSC infusions in refractory JIA patients are safe, although in sJIA stopping the 'failing' biologic treatment carries a risk of a MAS flare since the drug might still suppress the systemic features. Furthermore, intravenous administration of MSC might be efficacious even in multiple biological-failing JIA patients with damage. <h3>Disclosure of Interest</h3> None declared
Enhancer Domains in Gastrointestinal Stromal Tumor Regulate KIT Expression and Are Targetable by BET Bromodomain Inhibition
Authors: Matthew L. Hemming, Matthew A. Lawlor, Jessica L. Andersen, Timothy Hagan, Otari Chipashvili, Thomas G. Scott, Chandrajit P. Raut, Ewa Sicinska, Scott A. Armstrong, George D. Demetri, James E. Bradner
Journal: Cancer Research (2019)

Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm characterized by activating mutations in the related receptor tyrosine kinases KIT and PDGFRA. GIST relies on expression of these unamplified receptor tyrosine kinase (RTK) genes through a large enhancer domain, resulting in high expression levels of the oncogene required for tumor growth. Although kinase inhibition is an effective therapy for many patients with GIST, disease progression from kinase-resistant mutations is common and no other effective classes of systemic therapy exist. In this study, we identify regulatory regions of the
THU0214 Predictive factors for achievement of low disease activity at 52 weeks are different between young and elderly rheumatoid arthritis patients treated with abatacept
Authors: N. Takahashi, T. Kojima, S. Asai, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Japanese post-marketing survey (PMS) data demonstrated that the clinical efficacy of abatacept was similar between the young and elderly rheumatoid arthritis (RA) patients, while they have quite different characteristics including age, disease duration, and concomitant drugs. We hypothesised that the predictive factors for clinical outcomes of abatacept were different between the young and elderly patients. <h3>Objectives</h3> We studied the predictive factors for good clinical response of abatacept in the young and elderly patients, respectively, in this study. <h3>Methods</h3> Participants were consecutive 463 RA patients treated with abatacept and observed for longer than 52 weeks in the TBCR, a Japanese multicenter registry system for RA patients treated with biologics. Univariate and multivariate logistic regression analysis was used to study predictive factors for achievement of low disease activity (LDA) at 52 weeks, separately in the young (&lt;65 years, n=215) and the elderly (&lt;65 years, n=248) group. <h3>Results</h3> Mean age was 55.3/74.0 years (young/elderly), disease duration was 10.2/12.8 years, DAS28-CRP was 4.34/4.40 at baseline, concomitant MTX was used in 55.4/37.1%, concomitant steroid was used in 51.0/49.6%, and proportion of bio-naïve was 49.3/63.3%. As shown in table 1, multivariate analysis revealed that no history of previous biologics and lower DAS28 score at baseline was the independent positive predictors in both young and elderly group. Interestingly, ACPA positivity was significant predictor only in the young group. The ACPA positive patients showed the significantly higher proportion of LDA achievement at 52 weeks, only in the young group (figure 1). <h3>Conclusions</h3> It has been reported that lower proportion of the elderly onset RA (EORA) patients has ACPA positivity, and some reports have previously demonstrated that the ACPA negative was negatively associated with good clinical outcomes of abatacept. Our current results suggested that the effect of ACPA positivity on the clinical results of abatacept treatment was different between ages. Abatacept would be a valuable treatment option in the ACPA negative elderly RA patients. <h3>Disclosure of Interest</h3> None declared
Impact of organisation and specialist service delivery on lung cancer outcomes
Authors: Jana Bhavani Adizie, Aamir Khakwani, Paul Beckett, Richard Hubbard, Neal Navani, Susan V Harden, Ian Woolhouse
Journal: Thorax (2019)

Introduction Data from the National Lung Cancer Audit (NLCA) often show variation in outcomes between lung cancer units which are not entirely explained by case mix. We explore the association between the organisation of services and patient outcome. Methods Details of service provision were collected via an electronic survey in June 2017. An overall organisational score derived from eleven key service factors from national lung cancer commissioning guidance was calculated for each organisation. The results for each hospital were linked to their patient outcome results from the 2015 NLCA cases. Multivariate logistic regression analysis was used to link the organisational score to patient outcomes. Results Lung cancer unit organisational audit scores varied from 0 to 11. Thirty-eight (29%) units had a score of 0–4, 64 (50%) had a score of 5–7 and 27 (21%) had a score of 8–11. Multivariate regression analysis revealed that, compared with an organisational score of 0–4, patients seen at units with a score of 8–11 had higher 1-year survival (adjusted OR (95% CI)=2.30 (1.04 to 5.08), p&lt;0.001), higher curative-intent treatment rate (adjusted OR (95% CI)=1.62 (1.26 to 2.09), p&lt;0.001) and greater likelihood of receiving treatment within 62 days (adjusted OR (95% CI)=1.49 (1.20 to 1.86), p&lt;0.001). Conclusion National variation in the provision of services and workforce remain. We provide evidence that adherence to the national lung commissioning guidance has the potential to improve patient outcomes within the current service structure.
SAT0320 Reliability analysis of the madrid sonographic enthesis index (MASEI) and different doppler subgroups in psoriatic arthritis
Authors: C. Macía Villa, S. Falcao, E. De Miguel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Enthesitis is the cornerstone of spondyloarthritis, and ultrasound (US) indexes have emerged in the last years being the Madrid Sonographic Enthesis Index (MASEI) one of the more widely used. <h3>Objectives</h3> To evaluate the reliability of MASEI and different enthesis power doppler (PD) definitions in Psoriastic Arthritis (PsA). <h3>Methods</h3> 27 consecutive non selected PsA patients were included. An US expert rheumatologist performed the MASEI examination using a MyLab 70 XVG machine, Esaote, Genova, Italy, with a greyscale (GS) 13 MHz probe and 7.1 MHz power Doppler (PD) frequency, PRF 750 Hz and 60 Gain. US images and 3–5 s videos were obtained in transversal and longitudinal views for further reliability analysis. The inter-reader reliability analysis was performed by three readers and true US result was the consensus of at least two of them. In addition to the PD item of MASEI (defined as signal in bone profile or intratendon or bursa on the enthesis area), three other PD definitions were evaluated as present or absent: PD OMERACT (PD signal at enthesis ≤2 mm to the bone profile), PD bursa (PD signal inside bursa) and PD tendon (PD signal in the enthesis tendon &gt;2 mm from the bone profile). Intraclass correlation coefficient (ICC) estimations and 95% confident intervals were calculated for the reliability analysis of MASEI and PD subgroups based on a mean-rating (<i>k</i>=3), absolute-agreement, two-way mixed effect model. Cohen`s Kappa test was used for analysis of MASEI's items reliability. SPSS statistical package version 20 (SPSS Inc, Chicago, IL) was used. <h3>Results</h3> Inter-reader reliability of MASEI and PD subgroups is shown in table 1. PD bursa showed the lowest reliability. MASEI, PD MASEI, PD OMERACT and PD tendon showed good to excellent reliability, being PD tendon the best one. table 2 shows reliability data of each MASEI lesion in each enthesis included in the index. Best agreement percentages and kappa values were found in erosions and PD with mainly good to excellent data, while the worst ones were found in calcifications with poor to moderate values. <h3>Conclusions</h3> MASEI has demonstrated to be a reliable tool in PsA. Erosions and PD showed the best reliability values. Evaluating different definitions of enthesis PD, signal in the tendon was the most reliable one, followed with minimal differences by PD MASEI and PD OMERACT, and in last place PD bursa. <h3>Disclosure of Interest</h3> None declared