tbuckley/cabot-search huggingface dataset:
THU0427 THE LIFETIME RISK OF KNEE AND HIP REPLACEMENT FOLLOWING A GP DIAGNOSIS OF OSTEOARTHRITIS: REAL WORLD COHORT DATA FROM CATALONIA INCLUDING 48,311 PARTICIPANTS WITH UP TO 9 YEARS OF FOLLOW-UP
Authors: Edward Burn, David W Murray, Gillian A Hawker, Rafael Pinedo-Villanueva, Daniel Prieto-Alhambra
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The lifetime risk of knee and hip replacement following a primary care diagnosis of knee or hip osteoarthritis is unknown and overly negative beliefs about prognosis act as a barrier to implementing recommended management strategies. <h3>Objectives:</h3> To estimate lifetime risk of knee and hip replacement following a GP diagnosis of osteoarthritis and assess how this risk varies with patient characteristics. <h3>Methods:</h3> Primary care and linked hospital data from Catalonia, covering 2006 to 2015, were used. Study participants had a newly recorded GP diagnosis of knee or hip osteoarthritis. Parametric survival models were specified for risk of knee/hip replacement and death following diagnosis. Survival models were combined and extrapolated using a Markov model and lifetime risk estimated for the average patient profile. The effects of age at diagnosis, sex, comorbidities, socioeconomic status, body mass index (BMI), and smoking on risk were assessed. <h3>Results:</h3> 48,311 individuals diagnosed with knee osteoarthritis were included with a median follow-up of 4.3 years (IQR: 2.1 to 6.5) and of whom 2,561 underwent knee replacement. Respective figures for hip osteoarthritis were 15,105 individuals diagnosed with a median follow-up of 3.8 years (IQR: 1.8 to 6.1) and 1,247 hip replacements. The average participant's lifetime risk for knee replacement was 30% (95% CI: 25% to 36%) and for hip replacement was 14% (10% to 19%). Notable patient characteristics influencing lifetime risk were age at diagnosis for knee and hip replacement, sex for hip replacement, and BMI for knee replacement. BMI increasing from 25 to 35 was associated with lifetime risk of knee replacement increasing from 24% (20% to 28%) to 32% (26% to 37%) for otherwise average patients. <h3>Conclusion:</h3> Knee and hip replacement are not bound to happen for most after a GP diagnosis of osteoarthritis, with average lifetime risks of less than a third and a sixth, respectively. Patient characteristics influence lifetime risks with, most notably higher BMI associated with a meaningfully increased risk of knee replacement. <h3>Disclosure of Interests:&nbsp;:</h3> Edward Burn: None declared, David W Murray Grant/research support from: Grants from Zimmer Biomet, Consultant for: Personal fees from Zimmer Biomet, Gillian A Hawker: None declared, Rafael Pinedo-Villanueva: None declared, Daniel Prieto-Alhambra Grant/research support from: Grants from Amgen, UCB Biopharma and Servier outside the submitted work, Consultant for: UCB Biopharma, Speakers bureau: Amgen&nbsp;
AB0613 PRESENTATION OF TAKAYASU ARTERITIS ACCORDING TO THE AGE OF ONSET IN A MONOCENTRIC ITALIAN COHORT
Authors: Silvia Sartorelli, Corrado Campochiaro, Alessandro Tomelleri, Elena Baldissera, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Takayasu arteritis (TA) is a large-vessel vasculitis usually affecting young women. The age of onset is though variable. Controversial data are reported about differences in disease features according to the age of onset. <h3>Objectives:</h3> To compare clinical and vascular TA features according to TA age of onset. <h3>Methods:</h3> We retrospectively evaluated onset demographic and disease features in TA patients followed-up at our Hospital between January 2000 and august 2018. We divided our cohort into 3 groups according to the age of onset: ≤20 (Group 1), 21-40 (Group 2), &gt;40 (Group 3) years. Diagnostic delay (DD) was defined as the time interval between the first TA symptom and TA diagnosis. Non parametric statistic tests were used. <h3>Results:</h3> 126 patients (12 male, 114 female) were analyzed. Mean age at onset was 31.46±13.38 years. Group 1 and 3 included 30 (23.81%) patients each, Group 2 66 (52.38%). Mean age at onset was 16.23±3.20 years in Group 1, 29.59±5.80 in Group 2 and 50.8±7.16 in Group 3. Mean DD was different between the 3 groups: 117.63±129.79 months in Group 1, 56.47±76.98 in Group 2 and 30.80±40.53 in Group 3 (Group 1 vs 2, p=0.021; Group 1 vs 3, p&lt;0.001; Group 2 vs 3, p=0.089). Clinical and laboratory features at TA onset are summarized in Table 1. Among all disease features only arterial hypertension was statistically more prevalent in Group 3 vs Group 1 and 2 (56.67% vs 36.67% and 30.30% respectively, p=0.048). When evaluating vascular involvement, abdominal aorta was more frequently affected in Group 1 (63.33% vs 34.85% and 56.67%, p=0.018) while right iliac and left iliac arteries in Group 3 (40% vs 23.33% and 10.61%, p=0.004; 36.67% vs 23.33% and 12.12%, p=0.024 respectively). <h3>Conclusion:</h3> TA patients &lt;20 years might experience a longer DD. Arterial hypertension seems to be a prevalent feature in TA patients &gt;40 years. Vascular involvement seems also be influenced by the age of onset with the abdominal aorta being more frequently affected in younger patients and iliac arteries in older patients. <h3>Disclosure of interests:</h3> Silvia Sartorelli: None declared, Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., alessandro Tomelleri: None declared, Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from abbvie, amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.
Rise in inappropriate out of area mental health placements is “totally unacceptable”
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Seven NHS trusts made up more than half of all inappropriate out of area placements (OAPs) for acute mental health inpatient care between December 2018 and February 2019, according to data from NHS Digital.1

OAPs occur when a person requiring adult mental health acute inpatient care is placed in a unit outside of their local services, normally away from their family and care coordinator.

The government pledged to eliminate inappropriate mental health OAPs in mental health by 2020-21 as part of the Five Year Forward View.

The latest figures showed, however, that the number of inappropriate OAP …
Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations
Authors: Anthony G. Doran, Kim Wong, Jonathan Flint, David J. Adams, Kent W. Hunter, Thomas M. Keane
Journal: Genome biology (2016)

The Mouse Genomes Project is an ongoing collaborative effort to sequence the genomes of the common laboratory mouse strains. In 2011, the initial analysis of sequence variation across 17 strains found 56.7 M unique single nucleotide polymorphisms (SNPs) and 8.8 M indels. We carry out deep sequencing of 13 additional inbred strains (BUB/BnJ, C57BL/10J, C57BR/cdJ, C58/J, DBA/1J, I/LnJ, KK/HiJ, MOLF/EiJ, NZB/B1NJ, NZW/LacJ, RF/J, SEA/GnJ and ST/bJ), cataloguing molecular variation within and across the strains. These strains include important models for immune response, leukaemia, age-related hearing loss and rheumatoid arthritis. We now have several examples of fully sequenced closely related strains that are divergent for several disease phenotypes. Approximately 27.4 M unique SNPs and 5 M indels are identified across these strains compared to the C57BL/6 J reference genome (GRCm38). The amount of variation found in the inbred laboratory mouse genome has increased to 71 M SNPs and 12 M indels. We investigate the genetic basis of highly penetrant cancer susceptibility in RF/J finding private novel missense mutations in DNA damage repair and highly cancer associated genes. We use two highly related strains (DBA/1J and DBA/2J) to investigate the genetic basis of collagen-induced arthritis susceptibility. This paper significantly expands the catalogue of fully sequenced laboratory mouse strains and now contains several examples of highly genetically similar strains with divergent phenotypes. We show how studying private missense mutations can lead to insights into the genetic mechanism for a highly penetrant phenotype.
Abstract 3377: Autoantibodies against Cardiac Troponin I and their Impact on Improvement of Left Ventricular Function after Acute Myocardial Infarction
Authors: Florian Leuschner, Stefan Göser, Henning Steen, Lars Reinhardt, Renate Öttl, Jin Li, Stefan Zittrich, Gabriele Pfitzer, Evangelos Giannitsis, Hugo A Katus, Ziya Kaya
Journal: Circulation (2007)

Background: Cardiac troponins in blood are the most preferred markers of myocardial damage. It has been shown that the application of antibodies against cardiac troponin I (cTnI-Ab) can induce dila...
THE HEPCIDIN-ERYTHROFERRONE AXIS AND ITS RELATIONSHIP WITH ERYTHROPOIESIS IN DIFFERENT TYPES OF ANEMIA
Authors: R. Del Orbe Barreto, Arrizabalaga B. Amuchastegui, María M.J. Jose, María M.C. Isabel, M. G. Maite, P. P. Salvador, G. R. Sandra, R. A. M. Pilar, V. M. Ana
Journal: HemaSphere (2019)
FRI0371 ALTERED EXPRESSION OF LNCRNA NR_003542 AND NR_026756 IN ANKYLOSING SPONDYLITIS MIGHT BE ASSOCIATED WITH THE DISEASE ACTIVITY
Authors: Ting Yi, Yu-Feng Qing, Zi-Yi Tang, Jian-Xiong Zheng, Dan Wang, Qin Xiong
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> lncRNAs have been recognized as powerful regulators of numerous genes and pathways in the pathogenesis of inflammatory and autoimmune diseases, including SLE, RA, T1DM, MS, autoimmnue thyroid disease, Sjögren's syndrome psoriasis, and Crohn's disease[1]. The role of lncRNAs in the pathogenesis of Ankylosing Spondylitis (AS) is just beginning to be investigated <h3>Objectives</h3> To determine whether the altered expression of lncRNA NR_003542 and NR_026756 in peripheral blood of AS patients could provide insights into the pathogenesis of AS. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMCs) lncRNA NR_003542 and NR_026756 expression were measured in 30 active AS (AAS)group, 30 inactive AS (IAS) group and 30 healthy control (HC) subjects. Clinical characteristics of the subjects are summarized in Table1. <h3>Results</h3> 1. Clinical and laboratory characteristics of the three groups (Table 1) <i>BASDAI</i>: bath ankylosing spondylitis disease activity index, <i>BASFI</i>: bath ankylosing spondylitis functional index,<i>HLA-B27</i>:Human leukocyte antigen B27.<i>ESR</i>:erythrocyte sedimentation,<i>WBC</i>:leukocyte, <i>GLOB</i>: globulin, a: the <i>P</i> value of the non-parametric Mann-Whitney test. 2. Comparison of the two lncRNAs expression among the three groups (Figure 1) 3. Correlations between levels of two lncRNAs expression s and clinical data in AS patients (Figure 2) <h3>Conclusion</h3> Altered expression of lncRNA-NR_003542 and NR_026756 in peripheral blood of AS patients might be involved in the pathogenesis of AS, higher expression of lncRNA-NR_003542 and lower expression of NR_026756 might be as the biomarkers for the disease activity of AS, further study would be needed to expound on the exact role of the two lncRNAs in AS. <h3>References</h3> [1] Chatenoud, L. Immune therapies of autoimmune diseases: are we approaching a real cure?Curr Opin Immunol18, 710-7 (2006). <h3>Disclosure of Interests</h3> Ting Yi: None declared, Yu-Feng Qing Grant/research support from: Sichuan Youth Science and Technology (2016JQ0053), and the Department of Science and Technology of Sichuan Province (2018JY0257), Zi-Yi Tang: None declared, Jian-Xiong Zheng: None declared, Dan Wang: None declared, qin xiong: None declared
Neuroinflammation in Murine Cirrhosis Is Dependent on the Gut Microbiome and Is Attenuated by Fecal Transplant
Authors: Runping Liu, Jason D. Kang, R. Balfour Sartor, Masoumeh Sikaroodi, Andrew Fagan, Edith A. Gavis, Huiping Zhou, Phillip B. Hylemon, Jeremy W. Herzog, Xiaojiaoyang Li, Robert H. Lippman, Javier Gonzalez‐Maeso, James B. Wade, Siddhartha Ghosh, Emily Gurley, Patrick M. Gillevet, Jasmohan S. Bajaj
Journal: Hepatology (2019)

Cirrhosis and hepatic encephalopathy (HE) is associated with an altered gut-liver-brain axis. Fecal microbial transplant (FMT) after antibiotics improves outcomes in HE, but the impact on brain function is unclear. The aim of this study is to determine the effect of colonization using human donors in germ-free (GF) mice on the gut-liver-brain axis. GF and conventional mice were made cirrhotic using carbon tetrachloride and compared with controls in GF and conventional state. Additional GF mice were colonized with stool from controls (Ctrl-Hum) and patients with cirrhosis (Cirr-Hum). Stools from patients with HE cirrhosis after antibiotics were pooled (pre-FMT). Stools from the same patients 15 days after FMT from a healthy donor were also pooled (post-FMT). Sterile supernatants were created from pre-FMT and post-FMT samples. GF mice were colonized using stools/sterile supernatants. For all mice, frontal cortex, liver, and small/large intestines were collected. Cortical inflammation, synaptic plasticity and gamma-aminobutyric acid (GABA) signaling, and liver inflammation and intestinal 16s ribosomal RNA microbiota sequencing were performed. Conventional cirrhotic mice had higher degrees of neuroinflammation, microglial/glial activation, GABA signaling, and intestinal dysbiosis compared with other groups. Cirr-Hum mice had greater neuroinflammation, microglial/glial activation, and GABA signaling and lower synaptic plasticity compared with Ctrl-Hum mice. This was associated with greater dysbiosis but no change in liver histology. Pre-FMT material colonization was associated with neuroinflammation and microglial activation and dysbiosis, which was reduced significantly with post-FMT samples. Sterile pre-FMT and post-FMT supernatants did not affect brain parameters. Liver inflammation was unaffected. Conclusion: Fecal microbial colonization from patients with cirrhosis results in higher degrees of neuroinflammation and activation of GABAergic and neuronal activation in mice regardless of cirrhosis compared with those from healthy humans. Reduction in neuroinflammation by using samples from post-FMT patients to colonize GF mice shows a direct effect of fecal microbiota independent of active liver inflammation or injury.
Genomic Signature of Kin Selection in an Ant with Obligately Sterile Workers
Authors: Michael R. Warner, Alexander S. Mikheyev, Timothy A. Linksvayer
Journal: Molecular Biology and Evolution (2017)

Kin selection is thought to drive the evolution of cooperation and conflict, but the specific genes and genome-wide patterns shaped by kin selection are unknown. We identified thousands of genes associated with the sterile ant worker caste, the archetype of an altruistic phenotype shaped by kin selection, and then used population and comparative genomic approaches to study patterns of molecular evolution at these genes. Consistent with population genetic theoretical predictions, worker-upregulated genes experienced reduced selection compared with genes upregulated in reproductive castes. Worker-upregulated genes included more taxonomically restricted genes, indicating that the worker caste has recruited more novel genes, yet these genes also experienced reduced selection. Our study identifies a putative genomic signature of kin selection and helps to integrate emerging sociogenomic data with longstanding social evolution theory.
PS1260 EFFICACY OF MOGAMULIZUMAB IN PREVIOUSLY TREATED PATIENTS WITH LESS ADVANCED MYCOSIS FUNGOIDES: RESULTS FROM THE MAVORIC STUDY
Authors: P.L. Zinzani, J. Scarisbrick, M. Bagot, D.C. Fisher, C. Elmets, M. Duvic, M. Beylot‐Barry, E.J. Kim, J. Moriya, M. Leoni, L.J. Geskin
Journal: HemaSphere (2019)

Background: In the MAVORIC Phase 3 study, patients (pts) with previously treated mycosis fungoides (MF)/Sézary syndrome (SS) stage IB‐IVB who received mogamulizumab (MOGA) had significantly prolonged progression‐free survival and greater overall response rates (ORRs) compared to pts on vorinostat (VORI) (Kim et al. Lancet Oncol 2018). Less advanced MF (stage IB/IIA) is a chronic skin malignancy that can involve blood and lymph nodes and may require many lines of systemic therapy over the disease course. Aims: This post‐hoc analysis specifically examined efficacy and safety of the recently approved MOGA in stage IB/IIA MF pts. Methods: In MAVORIC, stage IB‐IVB MF/SS pts who were treated with ≥1 prior systemic therapy were randomized to MOGA or oral VORI. In the post‐hoc analysis, time to next treatment (TTNT) was defined as time to any therapy excluding topical steroids or focal radiation treatment. ORR was based on global composite response in 4 disease compartments – skin, blood, lymph nodes, and viscera – achieved at 2 consecutive visits at least 8 weeks apart. Individual compartment responses were also assessed. Results: A total of 85 pts with stage IB/IIA CTCL were included (MOGA, IB n = 15, IIA n = 21; VORI, IB n = 27, IIA n = 22). Overall, 24% (10/42) of IB pts and 28% (12/43) of IIA pts had received ≥6 prior therapies. Median TTNT with MOGA in IB pts was 11.5 months (mo) (95% CI, 1.4,16.0) compared to 3.1 mo (95% CI, 2.7, 5.3) with VORI; in IIA pts, median TTNT was 10.1 mo (95% CI, 5.5, 12.6) and 4.9 mo (95% CI, 2.4, 8.0), respectively. ORR in IB pts receiving MOGA and VORI was 20% (3/15) and 18.5% (5/27), respectively; ORR in IIA was 19% (4/21) and 0% (0/22), respectively. For stage IB and IIA, compartmental response rates with MOGA were – skin: 20% (3/15) and 38% (8/21), blood: 0% (0/2) and 75% (6/8), and lymph nodes: 0% (0/0) and 15% (3/20), respectively. Adverse events were generally manageable and consistent with the ITT population. Summary/Conclusion: Though MAVORIC was not powered to determine treatment effect by disease stage, this post‐hoc analysis of TTNT, ORR, and compartmental response in stage IB/IIA demonstrates meaningful clinical benefit with MOGA in previously treated, less advanced MF pts.
SAT0276 STUDY OF THE EPIDEMIOLOGICAL, CLINICAL AND ANALYTICAL CHARACTERISTICS IN PATIENTS WITH SYSTEMIC SCLEROSIS AND CANCER IN VALL D’HEBRON HOSPITAL
Authors: Maria Roca Herrera, Alfredo Guillén del Castillo, Eduardo Callejas Moraga, David Bernal Bello, Jorge Hernando Cubero, Natalia Iriarte Gay de Montella, Vicent Fonollosa Pla, Carmen Pilar Simeón-Aznar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Scleroderma or systemic sclerosis (SSc) is a systemic, chronic autoimmune disease characterized by great clinical heterogeneity. In recent years, studies have proven that there is a relationship between SSc and neoplasia. SSc is associated with an increased risk of certain types of cancer, particularly lung, liver, hematological, non-melanoma skin and urothelial cancer. Despite this increasement, the relative risk of developing cancer is still low in these patients. In the literature, neoplasms have been described in 3-11% of patients with SSc. <h3>Objectives</h3> Our objective is to analyze the epidemiological, clinical and analytical characteristics previously described as possibly linked to the development of a cancer in patients with systemic sclerosis (SSc) in the Vall d'Hebron Hospital cohort. <h3>Methods</h3> We analyzed 583 patients in the Vall d'Hebron Hospital cohort of SSc. The inclusion criteria were age &gt; 18 years and the diagnosis of SSc limited, diffuse and SSc sine scleroderma. The different variables were analyzed by univariate statistical analysis with SPSS v21. <h3>Results</h3> We included 521 patients with diagnosis from January 1985 to August 2016. 88.7% were women, with an average age of 53. 94 patients were diagnosed with neoplasia. The analyzed variables and their statistical significance and the types of cancer developed by our cohort patients are shown in <i>Fig 1</i>. <h3>Conclusion</h3> In the analyzed cohort, a slow pattern in capillaroscopy, positivity for Pm/Scl and the use of ARBs is associated with the development of neoplasia in patients with SSc. It has an inverse association the positivity of Scl70 (ATA I), the active pattern in capillaroscopy and the use of azathioprine and CCBs. In our cohort 94 patients with SSc have developed cancer. The most prevalent types of cancer were breast cancer, hematologic malignancies and lung cancer, as shown in the literature. <h3>References</h3> [1] Onishi A, Sugiyama D, Kumagai S, Morinobu A. Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies. Arthritis Rheum 2013; 65: 1913–21. [2] Bernal-Bello D, de Tena JG, Guillén-del Castillo A, et al. Novel risk factors related to cancer in scleroderma. Autoimmun Rev 2017. <h3>Disclosure of Interests</h3> None declared
AB1374-HPR THE EFFECTIVENESS OF BIOPSYCHOSOCIAL EXERCISE PROGRAM ON PAIN COPING IN PATIENTS WITH ANKYLOSING SPONDYLITIS AND FIBROMYALGIA
Authors: Aybüke Seven, Aykut Özçadırcı, Gamze Arın, Fatma Birgül Kumbaroğlu, Nur Banu Karaca, Ali Akdoğan, Edibe Ünal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Ankylosing spondylitis (AS) and fibromyalgia (FM) are rheumatic diseases with a high incidence in the community. Although many studies have been done on pain in these patient groups, the studies on coping with pain are very limited (1, 2). Bilişsel Egzersiz Terapi Yaklaşımı (BETY) is an exercise approach that developed in rheumatic patients. This approach has its own Biopsychosocial Questionnaire (BETY-BQ). This scale that assesses patients biopsychosocial status and includes the question about pain coping skill (3). <h3>Objectives</h3> The aim of this study is to the effectiveness of biopsychosocial exercise program on pain coping in with patients AS and FM. <h3>Methods</h3> Patients with AS and FM were included in the study and demographic data were recorded. Patients attended the BETY sessions for 8 weeks, 3 times a week for sixty minutes. BETY-BQ (3) was applied to individuals before and after 8 weeks. The answers to the question I don't know how to control my pain, which is the 5th question of the BETY-BQ scale, was recorded as 5-point Likert, ranging between yes-always to no-never. <h3>Results</h3> 47 women with AS (n = 30) and FM (n = 17) included in the study. The mean age was 41.83 11.24 and 43.35 8.86 and the body mass indexes were 26.385.15and 26.325.15 for the AS and FM patients, respectively. There was a statistically significant difference in the ability of AS subjects to cope with pain before and after the BETY intervention (p &lt;0.05), there was no significant difference between individuals with FM before and after BETY intervention (p&gt; 0.05) (Table 1). <h3>Conclusion</h3> Although both AS and FM are rheumatic diseases, it is known that FM patients experience more intense psychosocial stress. They are, therefore, resistant to change (4). We found that the positive change in pain coping skill seen in the AS group is not seen in FM group. It is concluded that FM patients regarding in pain coping strategies they need to attend exercise programs and need to be educated about pain coping skills for a longer period. <h3>References</h3> [1] Dean, L.E., et al., Global prevalence of ankylosing spondylitis. Rheumatology (Oxford), 2014. 53(4): p. 650-7. [2] Cabo-Meseguer, A., G. Cerda-Olmedo, andJ.L. Trillo-Mata, Fibromyalgia: Prevalence, epidemiologic profiles and economic costs. Med Clin (Barc), 2017. 149(10): p. 441-448. [3] NAL, E., et al., Romatizmalı hastalar iin bir yaşam kalitesi leğinin geliştirilmesi: madde havuzunun oluşturulması. Journal of Exercise Therapy and Rehabilitation, 2017. 4(2): p. 67-75. [4] Clauw, D.J., Fibromyalgia and related conditions. Mayo Clin Proc, 2015. 90(5): p. 680-92. <h3>Disclosure of Interests</h3> None declared