tbuckley/cabot-search huggingface dataset:
Carfilzomib Cardiovascular Disease: Use of the Atherosclerotic Cardiovascular Disease Score to Predict Cardiovascular Events in Multiple Myeloma Patients Treated with Carfilzomib
Authors: Ricardo Parrondo, Tracy Andrews, Rima M Panchal, Sejal Kothadia, Camille Johnson, Jieqi Liu, Giselle Alexandra Suero-Abreu, David H. Vesole, David S Siegel, Noa Biran
Journal: Blood (2018)
AB0543 Correlation between systemic lupus erythematosus disease activity and ocular signs in ophthalmologically asymptomatic patients
Authors: S.A. Fouad, S.M. Esmat Mahmoud Ali, A.R.L. Rezk Alnaggar, S. Mahfouz, M. Essam, H. El-Gendy
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease involving different organs and systems. Ocular manifestations of lupus may manifest as a presenting feature of the disease or as a complication that can be sight threatening. Almost any part of the eye and visual pathway can be affected by inflammatory or thrombotic processes yet ophthalmological assesment in those patients may be delayed. <h3>Objectives</h3> Detection of various ocular pathologies in ophthalmologically asymptomatic SLE patients using Optical Coherence Tomography (OCT), Fundus Fluorescein angiography (FFA), and fundus examination, in addition to studying the relation of between detected ocular changes and SLE disease activity assessed by SLEDAI score. <h3>Methods</h3> 26 ophthalmologically asymptomatic SLE patients recruited from Kasr Alainy hospital, Cairo University, and were subjected to comprehensive ocular assessment in the form of the measurement of visual acuity, fundus examination, FFA, and OCT. Hypertensive, diabetic and renal impairment patients were excluded. <h3>Results</h3> SLE patients were 25 females and 1 male, age mean of 25.15 (±8.6)years, SLEDAI mean 14 (±8.3), duration of illness mean 27 (±42.3) months. FFA showed that 38 out of 52 eyes (73%) had signs of pathological changes in the form of splinter haemorrhages, venular occlusion, diffuse mottling and optic nerve leakage and also degenerative changes which indicate chronicity, in the form of hyperflurorescence areas outside the arcades and pre-papillary areas and capillary dropouts. Besides; OCT detected changes in 67.3% of the examined eyes with 26.9% revealing degenerative thinning. There was significant correlation between disease activity and changes detected by FFA (p value 0.017), but neither the fundus findings nor the OCT pathological changes had correlation with disease activity. On the other hand, there was significant correlation between OCT changes and prolonged use of hydroxychloroquine more than 5 years (p value 0.032) and steroid intake for more than 3 month (p value 0.039). There was no correlation between FFA or OCT changes and proteinuria or anti-phospholipid antibodies. <h3>Conclusions</h3> FFA is can detect early retinopathy changes in patients of SLE which cannot be detected by fundus examination. FFA changes are correlating with disease activity. On the other hand, there was no correlation between OCT changes and disease activity. OCT is more sensitive to detect changes from hydroxychloroquine and steroids intake. <h3>References</h3> [1] Sivaraj, R.R., Durrani, O.M., Denniston, A.K., et al. (2007). Ocular manifestations of systemic lupus erythematosus. Rheumatology, 46(12), 1757–1762. [2] Larosa, M., Iaccarino, L., Gatto, M., et al (2016). Advances in the Diagnosis and Classification of Systemic Lupus Erythematosus, 8409(July). <h3>Disclosure of Interest</h3> None declared
Preclinical Activity of IRAK4 Kinase Inhibitor CA-4948 Alone or in Combination with Targeted Therapies and Preliminary Phase 1 Clinical Results in Non-Hodgkin Lymphoma
Authors: Robert N Booher, Grzegorz S. Nowakowski, Krish Patel, Matthew A. Lunning, Maria Elena S. Samson, Ruzanna Atoyan, Anna W Ma, Guang-Xin Xu, Steven Dellarocca, Holly Modafferi, Mylissa Borek, Zhidong Zhang, Jefferson Parker, Duncan Whitney, Hongwei Wang, David P Tuck, Anas Younes
Journal: Blood (2018)
Four things we need to know about extreme self-sacrifice
Authors: Harvey Whitehouse
Journal: Behavioral and Brain Sciences (2018)

Abstract A comprehensive explanation of extreme self-sacrifice would ideally clarify not only the proximate mechanisms leading to this behaviour, but also its developmental origins, its functions (if any), and its history. The theoretical framework set out in my target article has something to say about all of these dimensions, and many of the criticisms raised in the commentaries can therefore be addressed under those four main headings. In my response, I also discuss a set of proposals for further extending the framework. Finally, I conclude by distilling from the discussion a host of novel questions requiring further investigation.
Mutated nucleophosmin 1 as immunotherapy target in acute myeloid leukemia
Authors: Dyantha I. van der Lee, Rogier M. Reijmers, Maria W. Honders, Renate S. Hagedoorn, Rob C.M. de Jong, Michel G.D. Kester, Dirk M. van der Steen, Arnoud H. de Ru, Christiaan Kweekel, Helena M. Bijen, Inge Jedema, Hendrik Veelken, Peter A. van Veelen, Mirjam H.M. Heemskerk, J.H. Frederik Falkenburg, Marieke Griffioen
Journal: Journal of Clinical Investigation (2019)

The most frequent subtype of acute myeloid leukemia (AML) is defined by mutations in the nucleophosmin 1 (NPM1) gene. Mutated NPM1 (ΔNPM1) is an attractive target for immunotherapy, since it is an essential driver gene and 4 bp frameshift insertions occur in the same hotspot in 30%–35% of AMLs, resulting in a C-terminal alternative reading frame of 11 aa. By searching the HLA class I ligandome of primary AMLs, we identified multiple ΔNPM1-derived peptides. For one of these peptides, HLA-A*02:01–binding CLAVEEVSL, we searched for specific T cells in healthy individuals using peptide-HLA tetramers. Tetramer-positive CD8+ T cells were isolated and analyzed for reactivity against primary AMLs. From one clone with superior antitumor reactivity, we isolated the T cell receptor (TCR) and demonstrated specific recognition and lysis of HLA-A*02:01–positive ΔNPM1 AML after retroviral transfer to CD8+ and CD4+ T cells. Antitumor efficacy of TCR-transduced T cells was confirmed in immunodeficient mice engrafted with a human AML cell line expressing ΔNPM1. In conclusion, the data show that ΔNPM1-derived peptides are presented on AML and that CLAVEEVSL is a neoantigen that can be efficiently targeted on AML by ΔNPM1 TCR gene transfer. Immunotherapy targeting ΔNPM1 may therefore contribute to treatment of AML.
AB1054 Factors associated with tuberculosis in rheumatoid arthritis
Authors: O. Saidane, M. Sellami, I. Mahmoud, A. Ben Tekaya, H. Ajlani, R. Tekaya, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with infections that are favoured by the disease itself or by its treatments. Tuberculosis (TB) is a severe infection that can occur in patients with RA, especially with the use of anti TNF. <h3>Objectives</h3> We aimed to estimate the incidence of TB in RA patients and identify factors associated with TB during RA. <h3>Methods</h3> This is a retrospective study of RA patients according to ACR/,<sup>EULAR criteria 2010</sup> collected in rheumatology department during the period from April 2010 to April 2015. Diagnosis of latent or patent TB was made as part of the pretreatment screening (biotherapy) or if signs of infection occurred. <h3>Results</h3> During the study period, 150 RA patients (124 women and 26 men) were enrolled. The mean age was 57.09 years.<sup>25–85</sup> Mean disease duration was 7.52 years.<sup>1–26</sup> Rheumatoid Factor was positive in 79% of cases. Eighty eight per cent of patients received corticosteroids with a mean dose of 10 mg/day.<sup>5–20</sup> All patients were treated with at least one conventional synthetic disease-modifying antirheumatic drug (methotrexate, sulfasalazine and leflunomide in respectively 87%, 37% and 7% cases) and only 36 (24%) patients received biotherapy. A history of patent TB treated appropriately and prior to RA, was found in 5 patients (3%): 3 pulmonary TB and 2 lymph node forms. The pretreatrement test showed 11 cases of latent TB (30%). No relapsed TB was reported on RA treatment. Nine cases (25%) of new active TB were noted during biotherapy: 5 pulmonary TB (under infliximab, adalimumab and tocilizumab), 2 lymph nodes TB (under infliximab) and 2 urogenital TB (under infliximab). In our study, factors associated to TB infection were an advanced age, high level of C-reactive protein, a history of diabetes, dose of steroids≥7.5 mg/day and dose of Infliximab&gt;3 mg/kg (table 1). <h3>Conclusions</h3> Our study showed that RA patients were exposed to a higher risk of TB, especially when using anti TNF therapy with increased incidence of extra pulmonary TB. Understanding associated factors with TB may lead to establish a continuous monitoring in order to improve the quality of care. <h3>Disclosure of Interest</h3> None declared
THU0248 Association of kinesiophobia, aerobic exercise, functional impairment and disease activity of patients with rheumatoid arthritis and spondyloarthritis
Authors: D. peres, N. tordi, Y. sagawa, D. wendling, C. Prati
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) and spondyloarthritis (SA) are the most common chronic inflammatory rheumatism, leading to functional disability, but also cardiovascular mortality. Aerobic exercise (AE) is one of the most effective non-pharmacological resources for cardiovascular rehabilitation while the patients RA and SA have difficulty to join the practice of physical exercise. It can be explained by the presence of kinesiophobia, fear that the movement exacerbates the pain and disease. <h3>Objectives</h3> To compare the level of AE of patients with RA and SA with healthy subjects and to verify the association between kinesiophobia, the level of activity of the disease and the functional disability <h3>Methods</h3> Fifty RA patients and fifty SA patients followed by the rheumatology department of the University Hospital of Besançon and fifty healthy age-matched subjects were included. The main inclusion criteria: between 18 and 80 years old and without orthopaedic surgery &lt;1 year. The disease activity (DAS-28 and ASDAS), the functional disability (HAQ and BASFI), the level of AE (SQUASH questionnaire) and kinesiophobia (TSK questionnaire) were evaluated. The control group answered to the SQUASH questionnaire. The t-test was used to compare inflammatory rheumatism groups with the control group (healthy subjects). The Pearson Correlation Test for each group (RA and SA) was used to verify the associations between variables. <h3>Results</h3> The level of AE is significantly higher in healthy subjects (p=0.022). In the RA group, kinesiophobia is associated with disease activity, functional disability and level of AE. In the SA group, kinesiophobia is associated only with the functional disability. Patients have a low level of AE compared to healthy subjects. However, only the RA group has an association between kinesiophobia and AE. In the SA group, functional disability appears to be a factor limiting the practice of AE. <h3>Conclusions</h3> RA and SA patients need to be encouraged and better informed about the benefits of physical exercise. <h3>Disclosure of Interest</h3> None declared
FRI0189 Peripheral manifestations in spondyloarthritis: impact on patient-reported outcomes (PROS) and treatment. data from asas-comospa
Authors: C. López-Medina, A. Moltó, M. Dougados
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Peripheral manifestations (arthritis, enthesitis and dactylitis) are frequent in patients with Spondyloarthritis (SpA)<sup>1</sup>. However, little is known regarding the impact of these manifestations on patients' disease perception and treatments. <h3>Objectives</h3> To evaluate the impact of the presence of peripheral manifestations on patient-reported outcomes (PROs) and treatment. <h3>Methods</h3> Data from the ASAS-COMOSPA study were analysed. Patients who reported peripheral arthritis were divided into three groups: current, past history and no history. The impact of the presence of peripheral arthritis on VAS-G (Global Visual Analogue Scale), BASDAI (Bath Ankylosing Spondylitis Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index), work and activity impairment was evaluated through the use of the ANOVA one factor test. Finally, NSAIDs, corticosteroids and DMARDs intake were compared among patients with and without peripheral articular involvement. A similar statistical analysis was performed for enthesitis and dactylitis. <h3>Results</h3> Among the 3984 patients included in the ASAS-COMOSPA study, 1333 (33.5%), 718 (18%) and 1933 (48.5%) patients had current, past history and no history of peripheral arthritis, respectively. Patients with current peripheral arthritis showed higher levels in VAS-G, BASDAI, BASFI, as well as in work and activity impairment, in comparison to the other two groups, being these differences statistically significant (p&lt;0.01). Patients with peripheral articular involvement at the time of the visit showed higher mean scores in all questions of the BASDAI questionnaire, in contrast to those with past history and/or no history (p&lt;0.001). Impact on treatment is shown in table 1. Regarding enthesitis, 642 (16.1%), 864 (21.7%) and 2478 (62.2%) patients had current, past history and no history of enthesitis, respectively. Patients with current enthesitis showed significant higher levels in all PROs against the other two groups of patients (p&lt;0.05), as well as higher scores in all the BASDAI questions (p&lt;0.001). Finally, 171 (4.3%), 447 (11.2%) and 3366 (84.5%) patients had current, past history and no history of dacylitis, respectively. The same results as the other two peripheral manifestations were obtained regarding impact on PROs and BASDAI questions. <h3>Conclusions</h3> The presence of any of the three peripheral manifestations at the time of the visit was associated to higher scores in all PROs. Patients with peripheral involvement showed greater use of NSAIDs, corticosteroids and DMARDs than those without peripheral manifestations. <h3>Reference</h3> [1] Dougados M, d'Agostino MA, Banessiano J, et al. Joint Bone Spine2011Dec;78(6):589–603. doi:10.1016/j.jbspin.2011.01.013 <h3>Disclosure of Interest</h3> None declared
THU0575 Anakinra for first line steroid free treatment in systemic onset juvenile idiopathic arthritis
Authors: G. Horneff, A.C. Schulz, A. Klein, K. Eising
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic juvenile idiopathic arthritis (sJIA) is characterised by arthritis accompanied or preceded by systemic autoinflammation. High-dose steroids has been the mainstay of therapy with proven effectiveness but also with side-effects. In many patients a chronic course with destructive arthritis long-term cannot be prevented. <h3>Objectives</h3> In patients naïve for steroids, a steroid-free treatment may allow reconstitution of an impaired NK-cell function and probably remission of sJIA. <h3>Methods</h3> First experience with first line Anakinra without steroids in 9 consecutive patients is reported. <h3>Results</h3> All patients presented with ongoing spiking fever and rash and further features of sJIA, high CRP, S100 and IL18 (table 1). Daily sq. injections of Anakinra 2 mg/kg for 3 months resulted in complete remission in 4 and partial response in two children presenting with an oligoarticular involvement. One patient with typical sJIA and very high S100 (MRP8/9) levels did not respond to Anakinra nor to Canakinumab. Two patients presented with polyarthritis. One had no response, the other showed a minor response but improved on steroids and was later treated with tocilizumab. One of the oligoarticular patients with an initial partial response had a flare upon anakinra captured by increased dosing (4 mg/kg) but finally developed macrophage activation syndrome. Anakinra was discontinued after 3 months in 3 of the 4 responders. Two remained in drug free remission while the remainder flared several months later and retreatment was instituted. The patients with polyarticluar involvement first received corticosteroids and were later both treated successfully with the IL-6 inhibitor. <h3>Conclusions</h3> Experience with first line steroid free treatment with Anakinra for sJIA is presented. A complete remission was reached in 4 cases with oligoarticular involvement. In 3 further cases improvement was observed and 2 had no response including one who also failed Canakinumab. A toddler with a particular response to Anakinra later on developed MAS. One patient did not respond to both IL-1 inhibitors. Thus, steroid free treatment regimen with Anakinra is feasible and resulted into remission in most but not all patients. Aside, unwarranted effects of long lasting steroid application were avoided. <h3>Disclosure of Interest</h3> None declared
SAT0446 Serum concentrations of 25-hydroxyvitamin d and metabolic syndrome and its components in nondiabetic systemic lupus erythematosus patients
Authors: M. García-Carrasco, C. Mendoza Pinto, M. Cabrera-Jiménez, S. Méndez-Martínez, I. Etchegaray-Morales, I. Zamora-Guinez, A. Ruiz-Arguelles, R. Cervera
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Increasing evidence has suggested a protective role of vitamin D in the metabolic syndrome (MetS). However, studies addressing this issue are limited in systemic lupus erythematosus (SLE). <h3>Objectives</h3> We examined the relationship between serum 25-hydroxyvitamin D (25(OH)D) status and MetS in nondiabetic SLE patients. <h3>Methods</h3> Cross-sectional analyses of the relationship between concentrations of 25(OH)D, MetS, and its components were made in 160 nondiabetic SLE women. MetS was defined according to the NCEP-ATP III criteria. Serum 25(OH)D was measured by chemiluminescent immunoassay. Serum 25(OH)D levels were categorised into quartiles (&lt;16.6, 16.6–21.1, 21.2–26.3,≥26.4 ng/ml). <h3>Results</h3> A total of 79 (49.3%) of SLE women had MetS. Without adjusting for BMI or smoking, the odds of having MetS decreased according to increasing quartiles of vitamin D levels (P for trend=0.036). The odds ratio (OR) of having MetS was 0.39 (95% confidence interval: 0.16–0.97, p<i>=</i>0.043) for the highest <i>vs.</i> the lowest quartile of vitamin D levels when adjusted by age. The crude OR of having elevated hypertriglyceridemia decreased according to increasing quartiles of vitamin D levels (P for trend=0.036). However, further adjustments for BMI and smoking removed the inverse association between vitamin D status and MetS and its individual components (Table). <h3>Conclusions</h3> In nondiabetic SLE women with mild activity, the potential inverse relationship between vitamin D status and MetS may be attributable to the joint effects of individual obesity and smoking. Prospective studies are necessary to better determine the role of 25(OH)D in the incidence of MetS in SLE patients. <h3>Reference</h3> [1] Wang X, Yan S, Liu C, Xu Y, Wan L, Wang Y, et al. Fracture risk and bone mineral density levels in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Osteoporos Int2016:1413–1423. <h3>Acknowledgements</h3> We thank David Buss for his valuable advice during this project. <h3>Disclosure of Interest</h3> None declared
THU0305 Minimal disease activity (MDA) attainment after starting biological (B) dmards and non-bdmards treatment in psoriatic arthritis patients (PTS) in routine care: russian psoriatic arthritis registry (RU-PSART) data
Authors: E. Loginova, T. Korotaeva, A. Koltakova, E. Gubar, Y. Korsakova, E. Nasonov, A. Lila, M. Sedunova, T. Salnikova, I. Umnova, I. Bondareva, U. Zagidulina, P. Zemtsova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> MDA is a valid instrument for evaluating PsA treatment results. There is limited data about MDA attainment after starting bDMARDs and non-bDMARDs in routine care. RU-PsART collected data from 25 rheumatology clinics in the Russian Federation. <h3>Objectives</h3> evaluate MDA attainment after starting bDMARDs and non-bDMARDs treatment in PsA pts in routine care. <h3>Methods</h3> 294 (M/F–133/161) pts with PsA, diagnosed according to CASPAR criteria, mean age 41.2±1.9 (Min 21 – Max 72) years (yrs.), PsA duration 6.1±5.3 (Min 0 – Max 31) yrs., psoriasis duration 13.6±10.7 (Min 0.2 – Max 54.8) yrs. were included in the RU-PsART after signing consent participation forms. The present analysis included 274 pts who have data concerning PsA activity, treatment and MDA. The number of pts who reached MDA at least once were calculated. At the time of evaluation 81 out of 274 pts (29.6%) were taking bDMARDs±sDMARDs Infliximab (25 pts), Etanercept (16 pts), Adalimumab (14pts), Ustekinumab (8pts), Golimumab (5pts), Sekukinumab (2pts). 193 out of 274 pts (70.4%) were taking other types of treatment - sDMARDs±NSAID, mostly methotrexate (74.2%), sulfasalazine (12%), leflunomide (3.6%), hydroxichlorochine (0.4%); steroids (9.8%). All pts underwent evaluation of PsA activity by DAS28, CRP, Pt/Physician GA, Pain GA by VAS (0–100 mm), swollen/tender joints count (SJC/TJC), DAPSA and considered REM≤4/LDA≤14. M±SD, Me [Q25; Q75], Min-Max,%, U-test, ORs with 95% CI were performed. All CI &gt;1, p≤0.05 were considered to indicate statistical significance. <h3>Results</h3> At time of evaluation 60 out of 274 pts (21%) reached MDA at least once. Mean duration of sDMARDs and bDMARDs±sDMARDs was 11<sup><sup>6;17</sup></sup>/Min 3 - Max 204 months and 9<sup><sup>7;15</sup></sup>/Min 2 - Max 82 months accordingly. 28 out of 193 pts (10.4%) taking sDMARDs achieved MDA. Among 81 pts taking bDMARDs±sDMARDs MDA was seen in significantly more cases - 32 pts (30.8%), OR=3.85 [CI 95% 2.11–7.01]. REM/LDA by DAPSA was found in significantly more cases compared to pts taking other therapies – in 50 out of 81 pts (61.7%) and in 56 out of 193 pts (29%) accordingly (p≤0.05, U-test). Pts who had ever taken bDMARDs±sDMARDs had significantly less PsA activity compared to those who had taken other types of treatment (table 1). <h3>Conclusions</h3> MDA was seen in 21% of PsA pts in routine care but starting bDMARDs has a significantly higher probability of reaching MDA in most cases despite duration of treatment. <h3>Disclosure of Interest</h3> None declared
Realist Synthesis for Public Health: Building an Ontologically Deep Understanding of How Programs Work, For Whom, and In Which Contexts
Authors: Justin Jagosh
Journal: Annual Review of Public Health (2019)

Realist synthesis is a literature review methodology for understanding how, for whom, and under what circumstances complex interventions function in complex environments. Using a heuristic called the context-mechanism-outcome (CMO) configuration, realist synthesis produces evidence-informed theories about the interactions between intervention mechanisms and their implementation contexts. Public health interventions and their effects unfold over time and develop differently in different contexts. Much of what causes programs to function remains in a realm beyond empirical measurement. By scrutinizing the theories relevant to the interventions of interest, and by enhancing the conceptualization of complex outcomes, the realist approach deprioritizes evidence hierarchies and harnesses insights from diverse data sources to generate causal understanding. The dynamic learning process that can arise in conducting a realist synthesis may generate new ideas for program development and innovation apart from what can be achieved in reviews providing a summation and aggregation of quantified evidence.