tbuckley/cabot-search huggingface dataset:
AB0155 Learning sle pathological mechanisms from multi 'omics profiles
Authors: SS Pfister, N Kelley, T Schlitt, A Fernandez, M Sultan, M Hasan, A Mir, JS Rush
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Precision medicine aims at providing intervention based on clinical and molecular stratification of patients, and is an important approach for targeting heterogeneous diseases. A diverse autoimmune disease is systemic lupus erythematosus (SLE), where dysregulation of several immune processes affects multiple organs. Fundamental for targeted treatment of such a heterogeneous disease is the identification of biomarkers predictive for the biological basis of clinical phenotypes. <h3>Objectives</h3> Despite recent progress, few markers for SLE are currently used in the clinic. In order to learn SLE pathological mechanisms and associated biomarkers, we obtained a diverse dataset from a cohort of active SLE patients (SLEDAI &gt;6), including blood transcriptomics, serum proteomics, cytokines, and auto-antibody profiles. Integration of multi-omics data provides a rich dataset to explore associations between molecular and clinical readouts. <h3>Methods</h3> From a machine-learning perspective, biomarker discovery is defined as the process of selecting an optimal subset of variables for the prediction of parameters of interest. However, variable selection approaches are often underpowered for datasets that contain fewer samples than the number of variables. To overcome this problem we present a method based on L1 regularized regression and recursive variable elimination to generate networks of predictive markers across multiple data types. <h3>Results</h3> The proposed method allows us to graphically visualize the relationships among SLE phenotypes, and their molecular fingerprints. Identified networks of markers are validated by mapping to known biological pathways, and when available by comparison to independent patient cohorts. Despite the small number of patients (n=20), we identify known pathological mechanisms, including a type I IFN gene signature, several cell type specific signatures, and potential novel markers of clinically defined SLE subtypes. <h3>Conclusions</h3> Systemic lupus erythematosus is a complex autoimmune disease characterized by a variety of clinical manifestations. While multi-omics profiles from SLE patients pose challenges because of their intrinsic high dimensionality, they also provide a unique insight into the molecular processes of disease. Our integrated analysis gives a novel perspective on the pathological mechanisms of clinical SLE phenotypes. <h3>Disclosure of Interest</h3> None declared
AB0965 Evaluation of bone mineral density in children with chronic recurrent multifocal osteomyelitis at diagnosis
Authors: Ö Sert, E Çomak, G Kaya Aksoy, A Gemici, M Koyun, S Akman
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disorder that has sterile bone inflammation as a main phenotypic feature. Diagnosis of CRMO is based on typical clinical and radiologic findings and presence of some inflammatory markers. Plain radiographs, technetium bone scan and MRI may be used for diagnosis of children with suspected CRMO. Despite data for other imaging methods in chidren with CRMO, little information is available regarding the bone mineral density. <h3>Objectives</h3> The aim of the study was to evaluate bone mineral density (BMD) findings in children with CRMO at time of diagnosis. <h3>Methods</h3> The medical records of children with CRMO were reviewed retrospectively. Children who met Bristol diagnostic criteria were included in the study. Clinical and laboratory findings, bone scan and MRI features were analyzed. Bone mineral density was measured by DEXA technique at femoral neck and lumbar spine regions; a Z-score$&lt;-$2 was considered as osteoporosis. <h3>Results</h3> A total of 6 patients, one girl and 5 boys, with a median age of 10 years (4 – 14 years) and a median follow-up period of 38.5 months (3 – 72 months) were included in the study. MRI and whole body technetium bone scan were performed at 6 and 4 children, respectively and detected at least two lesions MRI or bone scans. Osteoporosis was detected in 5 patients at diagnosis. Bone mineral density Z-scores were median -2.9 [-4.9±(-2,4)] and -2.9 [-4,1 – (-1,8)] at femoral neck and lumbar spine, respectively. <h3>Conclusions</h3> Osteoporosis is common in children with CRMO, it may be related with disease spectrum. Evaluation of bone mineral density abnormalities at time of diagnosis and during therapy may be a part of primary care in children with CRMO. <h3>Disclosure of Interest</h3> None declared
AB0604 Rituximab experience in patients with longstanding systemic sclerosis-associated interstitial lung disease: a series of 14 patients
Authors: A Sari, D Guven, B Armagan, L Kilic, A Erden, A Akdogan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc) patients. Treatment options are rather limited in SSc associated ILD (SSc-ILD). <h3>Objectives</h3> Objective of this study was to report the experience of RTX treatment in a series of patients with longstanding SSc-ILD in whom unsatisfactory response in lung functions was noted under conventional treatments. <h3>Methods</h3> We retrospectively reviewed charts of 197 SSc patients evaluated between April 2015 and November 2016. 14 patients who received rituximab (RTX) for SSc-ILD participated in this analysis. The severity of ILD based on PFTs was defined as follows; mild (FVC between 71% and 80% of predicted), moderate (FVC between 51% and 70% of predicted) and severe (FVC ≤50%). The extent of skin disease was clinically measured by using Modified Rodnan Skin Score (mRSS) tool. End of follow-up was considered as six months after the last RTX dose. <h3>Results</h3> Median (IQR, interquartile range) age was 53.2 (46.8–55.5) and median disease duration was 9.1 (5.1–13.6) years. Median FVC was 52.5 (41.5–64.0) prior to RTX. At the end of follow-up, no significant change was revealed in FVC when compared with pre-RTX values [58.0 (44.7–58.7), p=0.065]. FVC was improved in four patients and stabilized remaining ten patients. All of the patients with improvement of PFTs had moderate or severe restrictive lung disease. High resolution thorax computed tomography (HRCT) findings remained stable in 7 and showed progression of ILD in 3 patients. In total, mRSS remained stable at the end of follow-up when compared with baseline [8.0 (5.2–12.2) vs. 6.0 (4.0–12.2),p=0,026]. <h3>Conclusions</h3> In this case series of SSc patients treated with RTX, improvement or stabilization of pulmonary functions was observed in most of SSc patients. RTX may be useful in SSc-ILD patients with longer disease duration and resistant to conventional immunsupresive therapies. <h3>Disclosure of Interest</h3> None declared
FRI0547 Osteoporosis and bone metabolism in systemic sclerosis
Authors: Ά Horváth, K Gulyás, HP Bhattoa, G Szücs, Z Szekanecz, S Szamosi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) has been associated with bone loss and increased risk for bone fractures. Disease-related factors, age, corticosteroid therapy may be associated with increased bone turnover and bone loss. <h3>Objectives</h3> Here we performed a detailed study on osteoporosis in SSc. We performed bone density assessment by DXA, as well as peripheral forearm quantitative CT (pQCT). In addition, we assessed bone biomarkers and correlated bone- and disease-associated measures. <h3>Methods</h3> Altogether 44 SSc patients (36 women, 8 men; age: 64.1 years; disease duration: 17.6 years) were randomly recruited for the study. Bone density was assessed by DXA at the lumbar spine and femoral neck. pQCT (Stratec) is able to assess total, trabecular and cortical density. We also determined FRAX, levels of vitamin D, as well as bone markers (Ca, PTH, osteoclacin, P1NP, beta-CTX), markers of autoimmunity (ANA, ACA and anti-Scl70) and clinical manifestations of the disease. Statistical analysis was performed by SPSS v22.0. <h3>Results</h3> Vitamin D levels were lower (53.9 +/- 36.8 nM) than the normal range (&gt;75 nM). 34 out of 44 patients (77%) had D-hypovitaminosis. Abnormally increased PTH, P1NP, OC, CTX levels were observed in 10, 7, 2 and 6 patients, respectively. Previous fractures occurred in 19 patients (43%). The vertebral and hip FRAX values were 13.5% and 4%&gt;respectively. By DXA, osteoporosis of the lumbar spine and hip was detected in 10 and 10 patients, while osteopenia were found in 16 and 20 patients, respectively. With respect to pQCT, total and trabecular bone density in SSc patients (248.4 and 150.9 mg/cm<sup>3</sup>) was significantly lower than in healthy controls (354 and 193 mg/cm<sup>3</sup>, respectively). Higher OC levels were assocated with the diffuse form of SSc (R=0.330, p=0.035). Longer disease duration correlated with lower pQCT total (R=-0.341, p=0.023) and trabecular density (R=-0.336, p=0.026). Interestingly, most bone markers (P1NP, OC, CTX) positively correlated with gastrointestinal manifestations. Furthermore, pQCT total bone density was siognificantly lower in patients with pulmonary involvement, digital ulcer and anti-Scl70+. <h3>Conclusions</h3> A high proportion of SSc patients have osteopenia or osteoporosis, as well as low vitamin D levels. As determined by pQCT, trabecular loss is more common. Both total and trabecular bone loss, as well as bone markers may be associated with disease duration, anti-Scl70 and some organ manifestations. SSc patients should be screened and treated for osteoporosis. <h3>Disclosure of Interest</h3> None declared
Trend and Geographic Variation in Cancer Mortality and Prevalence, With Special Reference to Gastric Cancer&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Selwyn D. Collins, Mary Gover, Harold F. Dorn
Journal: JNCI Journal of the National Cancer Institute (1941)

Trend and Geographic Variation in Cancer Mortality and Prevalence, With Special Reference to Gastric Cancer Get access Selwyn D. Collins, Selwyn D. Collins principal statistician Public Health Methods, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary Gover, Mary Gover associate statistician Public Health Methods, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold F. Dorn Harold F. Dorn senior statistician Public Health Methods, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 4, February 1941, Pages 425–450, https://doi.org/10.1093/jnci/1.4.425 Published: 01 February 1941
AB1083 Work impairment in patients experiencing musculoskeletal pain
Authors: NM Higgins, A Cochrane, CJ Rothwell, O FitzGerald, P Gallagher, J Ashton, R Breen, A Brennan, O Corcoran, D Desmond
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Many individuals with musculoskeletal disorders (MSD) continue to work. Little is known about those who remain occupationally active relative to those who are on sick leave, despite the clear potential for reduced productivity or work ability, and associated downstream effects. <h3>Objectives</h3> To assess self-reported work impairment and its associations with psychosocial risk factors amongst workers seeking care for musculoskeletal pain. <h3>Methods</h3> Recruitment took place in five Irish hospitals. Self-report questionnaires were used to assess risk of progressing to long-term sick leave and work disability (Örebro Musculoskeletal Pain Screening Questionnaire; ÖMPSQ), work ability, work impairment (WPAI) and work performance (WRFQ). <h3>Results</h3> 155 patients (53.5% female; mean age =46.50 years (range 20 to 71)) completed the questionnaire. 25.2% (n=39) were at high risk of progressing to long-term sick leave and work disability according to the ÖMPSQ. 62.6% (n=97) were classified as functioning poorly according to the WRFQ; 52.3% reported having poor work ability (n=81). Higher work role functioning was associated with higher pain self-efficacy (OR =1.514); better work ability was associated with older age (OR =1.063) and poorer function (OR =0.929); absenteeism was associated with lower pain self-efficacy (OR =0.650) and higher return to work expectancy (OR =1.179). Presenteeism was associated with higher pain intensity (β =0.259) and lower pain self-efficacy (β = - 0.385). <h3>Conclusions</h3> MSDs affect many individuals ability to work effectively. While all participants have managed to stay at work despite decreased levels of work ability and functioning, approximately a quarter are at high risk of progressing to long-term sickness absence. Interventions that attempt to improve mutable factors, such as pain self-efficacy, may help reduce the likelihood of work disability. <h3>Acknowledgements</h3> This research is funded by the Health Research Board [RCQPS-2014–2]. <h3>Disclosure of Interest</h3> None declared
A Highly Specific Genome-Wide Association Study Integrated with Transcriptome Data Reveals the Contribution of Copy Number Variations to Specialized Metabolites in Arabidopsis thaliana Accessions
Authors: Kazumasa Shirai, Fumio Matsuda, Ryo Nakabayashi, Masanori Okamoto, Maho Tanaka, Akihiro Fujimoto, Minami Shimizu, Kazuo Shinozaki, Motoaki Seki, Kazuki Saito, Kousuke Hanada
Journal: Molecular Biology and Evolution (2017)

Lineage-specific gene duplications contribute to a large variation in specialized metabolites among different plant species. There is also considerable variability in the specialized metabolites within a single plant species. However, it is unclear whether copy number variations (CNVs) derived from gene duplication events contribute to the diversity of specialized metabolites within species. We identified metabolome quantitative trait genes (mQTGs) associated with quantitative metabolite variations and examined the relationship between mQTGs and CNVs. We obtained 1,335 specialized metabolite signals from 53 worldwide A. thaliana accessions using liquid chromatography-quadrupole time-of-flight mass spectrometry. In this study, genes associated with specialized metabolites were inferred by either a generally authorized genome-wide association study (GWAS) approach or a novel analysis of the association between gene expression and metabolite accumulation. Genes qualified by both analyses are defined to be mQTGs. The integrated method enabled us to detect mQTGs with a low false positive rate (=5.71 × 10-4). We also identified 5,654 genes associated with 1,335 specialized metabolites. Of these genes, 4.4% were affected by CNVs, which was more than expected (χ2 test: P < 0.01). This result suggests that CNVs contribute to variations in specialized metabolites within a species. To assess the contribution of CNVs to adaptive evolution in A. thaliana, we examined the selective sweeps around the mQTGs. We observed that the mQTGs with CNVs tended to undergo selective sweeps. These observations imply that variations in specialized metabolites caused by CNVs contribute to the adaptive evolution of A. thaliana.
Margaret McCartney: Are we reviewing GP referrals for the right reasons?
Authors: Margaret McCartney
Journal: BMJ (2017)

NHS England wants all GP referrals to secondary care to be peer reviewed, and it believes that this can reduce referrals by “up to 30%.”1 The plans have met with shock and outrage in the tabloid press.

Outrage is justified, but for rather different reasons. This is yet another example of non-evidence based policy making, capable of doing more harm than good. And it’s not a new idea. The NHS has been looking at similar proposals for years.

The BMJ reported in January that a third of clinical commissioning groups have employed private companies to scrutinise referrals: three quarters were unable to show whether they’d saved …
131I Whole-Body Scan Incidental Uptake Due to Spermatocele
Authors: Domenico Albano, Federica Motta, Carla Baronchelli, Silvia Lucchini, Francesco Bertagna
Journal: Clinical Nuclear Medicine (2017)

A 46-year-old man with papillary thyroid cancer post total thyroidectomy was referred for post radioiodine (I) whole-body scan. Whole-body images revealed intense I uptake in the bed thyroid and a focal abnormal uptake in the testicular area. Subsequent SPECT/CT demonstrated that the focal uptake corresponded to the left epididymis, and the pathology report revealed a spermatocele with no immunohistochemical features for thyroid tissue. Many cases of unexpected radioiodine uptake have been reported, and spermatocele could be counted for another possibility of incidental I uptake despite an unclear mechanism.
FRI0542 Prevalence of vertebral body deformities related to osteoporosis in patients with non-traumatic lumbar or dorsal acute pain
Authors: CA Guillen-Astete, C Pijoán-Moratalla, JR Quiñones-Torres
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Presence of vertebral body deformities is considered a relevant issue in order to chose a particular treatment in patients with osteoporosis. However, only remarcable deformities are properly identified and registred while those, less striking can just be unnoticed in radiological studies not related to osteporosis studies. One of the most usual radiographic study of the axial skeleton is the lumbar and dorsal acute pain. This group of patients is, indeed, suitable stablish proportions of any grade of vertebral body deformities according to the Genant scale. <h3>Objectives</h3> The goal of present study is to determine prevalence of vertebral body deformities in postmenopausial patients radiologically assessed due to lumbar or dorsal non traumatic related pain. <h3>Methods</h3> We performed a simple randomization of the registries of female patients with 65 years old or more who consulted due to dorsal or lumbar non-traumatic acute pain, between 2014 and 2015. All included registries must had a radiological assessment. The gathering of registries concluded after reach 120% of the estimated sample size for a non finite theoretical population, a precision of 3% and a hypothetical estimated prevalence of 7% based on local previous studies of prevalence of vertebral osteoporotic fractures. Vertebral body measures were performed according to Genant scale recommendations from D7 to L5 as far as possible according to the field of study of the radiological chart plate. <h3>Results</h3> 275 randomized registries of dorsal and lumbar pain were included (total=550). Among patients with dorsal pain we identified 62 (22.5%), 30 (10.9%) and 18 (6.5%) vertebral deformities grade I, II and III respectively. Among patients with lumbar pain we identified 31 (11.2%), 49 (17.8%) and 33 (12%) vertebral deformities grade I, II and III respectively. Prevalence of any grade of dorsal vertebral deformity was 40.00% (CI 34.39 – 45.89) and lumbar was 41.09% (CI 95% 35.44 – 46.99). Lumbar vertebral body deformities grade I and II summed 70.7% while dorsal grade I and II summed 83.6%. From the 93 vertebral body deformities grade I, 6.4% were recognized in their clinical histories, 20.2% of the grade II deformities and 92.1% of the grade III deformities, (P&lt;0.001). <h3>Conclusions</h3> Although our population sample is circumscribed to symptomatic patients, our results contribute with prevalence of vertebral body deformities in postmenopausal patients grade I and II and who were mostly unnoticed. Proper identification of vertebral body deformities in patients with osteoporosis is crucial to decide treatment strategies in patients with known osteoporosis. Due to that, prevalence studies of this kind are relevant and useful to avoid diagnostic mistakes. <h3>Disclosure of Interest</h3> None declared
A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development
Authors: Yannick Boege, Mohsen Malehmir, Marc E. Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K. Ahuja, Friederike Böhm, Joachim C. Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J. Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M. Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J. Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A. Luther, Philipp J. Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R. Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Journal: Cancer Cell (2017)

Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
SP0195 Highlights from the health professional sessions
Authors: RJO Ferreira
Journal: Annals of the Rheumatic Diseases (2017)

EULAR congress is one on the biggest events in the world of rheumatology. To accommodate all the diversity of topics, several sessions take place at same time, in different rooms. It is very hard, even impossible, to be in all sessions, poster tours, social meetings and other learning events of your interest. It often happens that one want to be at 3 or 4 places at same time. This “Highlights” session is designed to summarize the most important conclusions of the talks given in all sessions from Health Professionals programme. By this way you can catch on what you missed to be in other places. Of course you can also read the abstracts in the EULAR app or Annals of Rheumatic Diseases Suplement or even to watch the podcasts after the event. However, this highlights session will provide you an integrated view of the different contents in a more appealing and interactive perspective. <h3>Disclosure of Interest</h3> None declared