tbuckley/cabot-search huggingface dataset:
AB0766 EVOLUTION OF BONE MINERAL DENSITYIN PATIENTS WITH PSORIASTIC ARTHROPATHY
Authors: L Montolio-Chiva, À Martínez-Ferrer, Marta Aguilar-Zamora, Ana V. Orenes Vera, I Vázquez-Gómez, C Vergara-Dangond, A Sendra-García, Elia Valls-Pascual, D Ybáñez-García, V Núñez-Monje, I Torner-Hernández, Juanjo J. Alegre-Sancho
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Some studies indicate that psoriatic arthritis (PsA) patients have increased bone loss due to chronic inflammation, but data in the Spanish population is scarce. <h3>Objectives:</h3> To study the evolution over time of bone mineral density (BMD) in patients with PsA and to investigate the factors related to these changes. <h3>Methods:</h3> We included PsA patients with peripheral joint involvement. They were treated at the Doctor Peset University Hospital and a 3-year follow-up was carried out. All patients underwent a bone densitometry and history of fracture was collected by conventional radiology at baseline and at 3 years. Phosphocalcic metabolism was also analyzed. We collected demographic and clinical variables [disease duration, DAS28, body mass index (BMI), smoking]. We considered 25OHD as deficient if &lt;20 ng/ml, low bone mass as T or Z scale &lt;-1 SD and osteoporosis as scale T &lt;-2.5 DE or Z &lt;-2 SD. Statistical analysis were performed with SPSS 22.0 program. <h3>Results:</h3> We included 91 patients (67,2% women), with a mean age of 56,4 (SD 1,2) years. The mean of disease duration was 104,9 (SD 11,8) months. The BMI mean was 27,6 (SD 0,5) and 36,3% of patients were smokers. 25OHD mean was 27.7 (SD 1.3) ng/ml and 33,3% of patients had a deficient 25OHD. More than half of the patients (53.8%) had low bone mass and 14.3% had osteoporosis, measured by densitometry. Twelve patients had history of fractures [6 distal forearm, 5 vertebral fractures (VF) and 1 of femur]. Thirteen patients received antiresorptive treatment [9 bisphosphonates, 3 denosumab and 1 selective estrogen receptor modulator (SERM)], and 39.6% of patients received 25OHD supplements. We did not observe any significant correlation between the 25OHD values and the activity parameters of the PsA. However, we observed lower levels of 25OHD in obese patients. At 3 years, the BMD remained stable in the majority of patients (68.1%) receiving antiresorptive treatment, and it worsened in 2 patients despite treatment with bisphosphonates. We registered new fractures in 7 patients (4 VF, 1 femur fracture and two patients had more than one fracture). New fractures were not correlated with age, 25OHD deficiency or with previous osteoporotic treatment. We observed greater progression of BMD in patients exposed to tobacco. <h3>Conclusion:</h3> More than half of patients with PsA have a low BMD (53.8%) and 33,3% deficient levels of 25OHD. Our study confirms results found in general population: classic risk factors, such as smoking, are related to BMI progression. It is important to evaluate BMD in these patients and intervene early. <h3>Disclosure of interests:</h3> None declared
Abstract MP023: Novel Patterns of Circulating Fatty Acids and Risk of Cardiovascular Disease: the Cardiovascular Health Study
Authors: Fumiaki Imamura, Rozenn N Lemaitre, Irena B King, Xiaoling Song, Alice H Lichtenstein, Nirupa R Matthan, David M Herrington, David S Siscovick, Dariush Mozaffarian
Journal: Circulation (2012)

Background: Circulating fatty acids (FA) reflect complex interrelations of diet and metabolism. Few studies have evaluated circulating FA as patterns related to cardiovascular diseases (CVD). Methods: We applied principal component analysis (PCA) to 39 plasma phospholipid FA measured in 2,972 older adults (mean age=72.1) at baseline (1992) in the Cardiovascular Health Study, and derived FA patterns. We evaluated prospective associations of identified FA patterns with 14-year incidence of CVD, adjudicated by centralized committee, using multivariate Cox proportional hazards corrected for regression dilution bias. The CHS-derived FA patterns were evaluated in a separate cohort for associations with angiographically-defined atherosclerosis progression over 3.5 years in 1,912 coronary segments of 228 postmenopausal women (mean age=65.4) with established CHD, including FA in phospholipids, triglycerides, and cholesteryl esters. Results: Three distinct patterns were identified, that we characterized as having higher trans FA (TFA pattern), de novo lipogenesis FA (DNL pattern), and dairy and long-chain monounsaturated FA (dairy-LCMUFA pattern). During 32,265 person-years, 780 CVD events occurred, including 512 CHD and 346 stroke. The TFA pattern was associated with higher CVD risk (HR for quintiles 5 vs. 1=2.47 [95% CI 1.35–4.51]; p trend=0.006) (Figure), primarily due to stroke (HR=4.68 [1.85–11.8]; p trend=0.003) but not CHD (HR=1.08 [0.50–2.32]; p trend=0.6). The DNL and dairy-LCMUFA patterns were not associated with CVD, or with CHD or stroke examined separately (p&gt;0.1). In the second cohort, the TFA pattern, but not the other 2 patterns, in all lipid compartments was positively associated with progression of coronary stenosis (p trend&lt;0.05). Conclusions: Our results suggest PCA can derive informative FA patterns for assessing disease risk. A pattern mainly reflecting higher trans FA levels is linked to higher risk of stroke in older adults, and coronary stenosis progression in women with CHD.
PS1552 THE INCIDENCE RATES AND RISK FACTORS OF ATYPICAL INFECTIONS IN PATIENTS WITH LYMPHOMA WHO RECEIVED AUTOLOGOUS STEM CELL TRANSPLANTATION
Authors: H.S. Lee, D.J. Kim, S.M. Jung, H. Lee, S. Jeong, S.G. Kong, S. Lee
Journal: HemaSphere (2019)

Background: Autologous stem cell transplantation (ASCT) is an intermediate risk group for infections according to National Comprehensive Cancer Network (NCCN) guideline. Based on the risk of infection, experts recommend prophylaxis for fungal infections with fluconazole or micafungin if mucositis is accompanied, and prophylaxis for Pneumocystitis jirovecii (P. jirovecii) infection with trimethoprim‐sulfamethoxazole (TMP‐SMX) for 3 to 6 months after transplantation. For varicella zoster virus (VZV) reactivation, acyclovir or famcyclovir or valacyclovir is recommended as prophylaxis for 6 to 12 months after ASCT. However, there is a lack of evidence to support this guideline. Aims: In this study we performed a nationwide population‐based study to provide information regarding the incidence and risk factors of atypical infections such as fungal, viral or PJP in patients were performed ASCT in the South Korea. Methods: Using the Korean Health Insurance Review and Assessment Service database, the patients with lymphoma who received ASCT from 2003 to 2016 were retrospectively analyzed. Atypical infection is identified by international classification of disease (ICD) codes of each infection or ATC(Anatomical Therapeutic Chemical) codes of medicines for treatment. Oral Candidiasis, Herpes simplex virus (HSV), and Epstein‐Barr virus (EBV) infection were excluded because these are considered to non‐pathogenic in clinical field. The patients undergoing allogenic stem cell transplantation (AlloSCT) were excluded. Results: The total number of patients with lymphoma undergoing ASCT was 2147, median age was 48 years (range 2–70). The cumulative incidence of fungal infection is 10.4%, viral is 20.0% and PJP is 5.5% in lymphoma. In multivariate analysis, TBI (HR 1.702, p = 0.0390), and previous fungal infection (HR 1.701, p = 0.0398) were independent significant risk factors for fungal infection. The multivariate analysis showed that TBI (HR 2.524, p &lt; 0.0001), previous infection history (HR 1.351, p = 0.0046) and prophylaxis (HR 1.633, p = 0.0001) were independent risk factors for viral infection. The multivariate analysis showed that prophylaxis (HR 2.647, p = 0.0002) were independent risk factors for PJP infection. Summary/Conclusion: In this study, patients with lymphoma who underwent ASCT showed relative high risk of viral infection (CIR 20.0%) and previous viral infection, TBI conditioning and non‐prophylaxis were independent risk factors for viral infection. So patients with lymphoma who planed ASCT should be considered prophylaxis for 2years after ASCT. Especially, patient who treated with TBI conditioning and have previous viral infection should receive prophylactic anti‐viral agents.
THU0030 THE DIFFERENTIAL EFFECT OF TNF-α AND IL-6R BLOCKERS ON THE EXPRESSION OF IL-17 AND ACTIVATED CD4+CD25+ T CELLS IN PATIENTS WITH PSORIATIC ARTHRITIS
Authors: Smadar Gertel, Ari Polachek, Victoria Furer, Daphna Paran, Ori Elkayam
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> TNF-α blockers are effective drugs for the treatment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). On the other hand, while interleukin-6 receptor (IL-6R) blockers have emerged as effective drugs in the treatment of RA, their effect in PsA has been disappointing. We hypothesized that the differential effect of TNF-α and IL-6R blockers in PsA may be mediated by the effect of these drugs on IL-17 expression, a cytokine profoundly involved in PsA and by their influence on activated CD4<sup>+</sup>CD25<sup>+</sup> T cells. <h3>Objectives</h3> To evaluate the differential effect of adalimumab (ADA) (representing TNF-α blockers) and tocilizumab (TCZ) (IL-6R blocker) on the expression level of IL-17 and on the frequency of activated CD4<sup>+</sup>CD25<sup>+</sup> T cells. <h3>Methods</h3> Levels of IL-17 mRNA expression were measured following <i>in vitro</i> co-culture of peripheral blood mononuclear cells (PBMC) derived from PsA patients with, ADA, TCZ at 10ug/ml or with medium alone as control for 3 days. Next, RNA was extracted and real-time PCR for IL-17 mRNA expression was performed. In addition, after 5 days incubation with the biologic agents the frequency of activated CD4<sup>+</sup>CD25<sup>+</sup> T cells were analyzed by flow cytometry. <h3>Results</h3> The differential effect of ADA and TCZ on IL-17 mRNA expression and modulation of activated CD4<sup>+</sup>CD25<sup>+</sup> T cells in culture of PBMC derived from PsA patients is shown in Figure 1. We found that IL-17 mRNA expression in PsA patients derived PBMC (n=20) was down-regulated by ADA. This down grading was significant in comparison with TCZ and medium control respectively (<i>p</i>&lt;0.0001, <i>p</i>=0.0003). On the other hand, TCZ significantly up-regulated the expression of IL-17 as compared to medium control (<i>p</i>=0.05) (Figure 1A). The frequency of activated CD4<sup>+</sup>CD25<sup>+</sup> T cells was down-regulated by ADA as compared to medium and TCZ, respectively (<i>p</i>=0.03, <i>p</i>=0.005). whereas activated CD4<sup>+</sup>CD25<sup>+</sup> T cells were up-regulated by TCZ (although not significantly) as compared to medium control (n=60) (Figure 1B). <h3>Conclusion</h3> Our data highlight the differential effect of ADA and TCZ on IL-17 expression level and on frequency of activated CD4<sup>+</sup>CD25<sup>+</sup> T cells in culture of peripheral immune cells derived from PsA patients. This data suggest a new mechanism of action of ADA and provide a possible explanation of the inefficacy of TCZ in PsA. <h3>Disclosure of Interests</h3> None declared
Archaic adaptive introgression in <i>TBX15/WARS2</i>
Authors: Fernando Racimo, David Gokhman, Matteo Fumagalli, Amy Ko, Torben Hansen, Ida Moltke, Anders Albrechtsen, Liran Carmel, Emilia Huerta-Sánchez, Rasmus Nielsen
Journal: Molecular Biology and Evolution (2016)

A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using single nucleotide polymorphism chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes, WARS2 and TBX15, and has previously been associated with adipose tissue differentiation and body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression of WARS2 and TBX15 in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and with regional DNA methylation changes in TBX15.
SP0092 ‘SCIENTIFIC DATA VISUALIZATION: FOCUS ON (POSTER) PRESENTATION
Authors: Maarten Boers
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> This practical skills session introduces the principles of good graph and table design as pioneered by Cleveland<sup>1</sup>and Tufte<sup>2</sup>and updated by Few<sup>3</sup>, this year focusing especially on (poster) presentation. Its learning objectives include: choosing the data visualization that best fits the data identifying the basics of table and graph design choosing tables and graphs that tell the story in the data introduction to poster design The session is linked to a special poster tour devoted to poster design on the next day: Poster tour 'F00" (note: this may be a temporary number), Friday 14-06-19, 11:50-13:30 (signup required!). Basics of table and graph design are also covered in my introductory YouTube clips on the ARD website (ard.com). Direct link: https://www.youtube.com/playlist?list=PLXU14EQbU_V9JpmolAKsaCC0VjJzbxzAN Also, I"ve recently published two articles on table and graph design which are freely downloadable.<sup>4,5</sup> When you download, don"t forget the online appendices, because they contain many useful examples! <h3>References:</h3> [1] Cleveland WS. The elements of graphing data: Hobart Press, Summit, NJ, USA; 1994. [2] Tufte E. The visual display of quantitative information. 2nd ed: Graphics Press, Cheshire, CT, USA; 2001. [3] Few S. Show me the numbers. Designing tables and graphs to enlighten. 2nd ed: Analytics Press, Oakland, CA, USA; 2012. [4] Boers M. Graphics and statistics for cardiology: designing effective tables for presentation and publication. Heart 2018;104:192-200 direct link: http://heart.bmj.com/cgi/content/full/heartjnl-2017-311581. [5] Boers M. Designing effective graphs to get your message across. Ann Rheum Dis 2018;77:833-9. direct link: http://ard.bmj.com/cgi/content/full/annrheumdis-2018-213396 <h3>Disclosure of Interests:</h3> None declared
Abstract 11602: Direct Evidence That Vascular Endothelial Protection Leads to aa Reduction of Heart Failure
Authors: Julie Maupoint, Jérémie Martinet, Elodie Gomez, Najime Bouhzam, Marie Besnier, Jean-Paul Henry, Olivier Boyer, Paul Mulder, Vincent Richard
Journal: Circulation (2015)

Introduction: Heart failure (HF) induces endothelial dysfunction, and especially decreases nitric oxide (NO) production, but the direct link between endothelial dysfunction and aggravation of HF is unknown. We previously reported a new treatment of endothelial dysfunction, based on inhibition of protein tyrosine phosphatase 1B (PTP1B), which both increases NO production and reduces cardiac dysfunction in HF. However the exact role of endothelial PTP1B in these effects is unknown. Hypothesis: Specific endothelial deletion of PTP1B reduces HF by limiting endothelial dysfunction Methods: Endothelial deletion of PTP1B was obtained by crossing LoxP-PTP1B mice with mice expressing Cre recombinase under the control of the endothelial promoter Tie2. Since this Tie2-Cre approach is known to also induce gene extinction in hematopoietic cells, Tie2Cre(+)PTP1Bf/f mice were also lethally irradiated and reinjected with bone marrow from wild type (WT; CD45.1) mice, in order to obtain a specific deletion of endothelial PTP1B (endoPTP1B-/- mice). All mice were then subjected to 4 months of myocardial infarction (MI) in order to induce HF, or to sham surgery Results: Vascular function evaluated ex vivo in mesenteric arteries (arteriograph) showed that in WT mice, HF markedly impaired endothelium-dependent, flow-mediated dilatation (sham: 40±4%; HF: 5±5; p&lt;0.001). This HF-induced endothelial dysfunction was less marked in Tie2Cre(+)PTP1Bf/f (MI: 30±5; p&lt;0.001 vs. WT) and in endoPTP1B-/- mice (35±6%). This improved response in endoPTP1B-/- mice were abolished by a NO-synthase inhibitor, suggesting a restored NO production. Evaluation of cardiac function by echocardiography showed that in WT, MI decreased left ventricular fractional shortening (sham: 49±2; HF: 12±1%; p&lt;0.001) and which was improved in Tie2Cre(+)PTP1Bf/f (26±1%; p&lt;0.01 vs. WT), and in endoPTP1B-/- mice (29±1%; p&lt;0.01 vs. WT). In parallel, endothelial PTP1B deficiency was associated with an increased survival. Conclusions: Endothelial PTP1B deficiency induced an improvement of endothelial function but especially improved cardiac function. These results provide a direct demonstration of the beneficial effect of endothelial protection in HF.
THU0406 ULTRASONOGRAPHIC INVOLVEMENT OF THE ANTERIOR CHEST WALL IN SPONDYLOARTHRITIS, A FIVE YEARS FOLLOW UP STUDY
Authors: Frank Verhoeven, Maxime Sondag, Mickael Chouk, Clément Prati, Daniel Wendling
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Spondyloarthrits is characterized by inflammatory back pain. Anterior chest wall pain is common and a previous study reported a prevalence à 37% of ultrasonographic lesions of this anatomical region [1]. <h3>Objectives</h3> The objective of this study is to evaluate, in patient with Spondyloarthritis, the prevalence of ACW ultrasonographic lesions after a follow up of 5 years and to identify factors associated with the development of new lesions. <h3>Methods</h3> This a monocentric and prospective study including patients with Spondyloarthritis meeting the ASAS 2009 criteria. Patients were followed during five years. ultrasound B mode and power Doppler examination of the two sternoclavicular joint and the manubrio-sternal joint were performed by the same two examinators at baseline and five years later. The presence of erosion, synovitis, ankylosis, power Doppler signal, joint effusion and bone margin narrowing were assessed. Clinical characteristics and disease activity were evaluated at 5 years. <h3>Results</h3> In the 136 patients at baseline, 58 patients were evaluated 5 years later. The mean age was 48.2 +/- 11.9 years old, with 86% male and 89% HLA B27. 60.3% of these patients had a history of pain of the ACW. The prevalence of ultrasonographic involvement of the ACW was 34% at baseline and 67.2% five years later. The most frequent lesions were ankylosis of the manubriosternal joint (38%) and erosions of the sternoclavicular joint (29%). At 5 years, patients with lesions of the ACW are significantly older (51.4 +/- 11.5 VS 41.5 +/- 9.98, p&lt;0,01). There were no differences concerning the presence of HLA B27 and the presence of a radiographic sacroilitis or syndesmophytes. Among these 58 patients, 31 (53%) developed a new lesion of the ACW. There is a statistically significant association between a higher ASDAS CRP and new lesions of the ACW (1,86 +/- 1,07 VS 3,0 +/- 2,17 p &lt; 0,01) and with the level of CRP (5,34 +/- 7,85 VS 16,2 +/- 35, p = 0,035). Baseline ASDAS CRP is not a predictor of new chest wall lesions prior to 5 years of age. Nevertheless, poor control of disease activity is associated with the development of new lesions. Patients with new lesions have an ASDAS CRP score that increase (0,882 +/- 2,48) between 2013 and 2018, while patients with no new lesions have an ASDAS CRP score that decrease (-0,641 +/- 1,50) between 2013 and 2018. <h3>Conclusion</h3> The prevalence of ultrasonographic lesions of the ACW increased after 5 years of follow up. The development of new lesions is associated with a higher disease activity, a higher CRP and an increased disease activity over 5 years. <h3>References</h3> [1] ]Verhoeven f. et al. Ultrasonographic evaluation of the anterior chest wall in spondyloarthritis: a prospective and controlled study.J Rheumatol. 2015;42:87-92. <h3>Disclosure of Interests</h3> None declared
PB2201 PROGRESS AND SURVIVAL IN TRIPLE NEGATIVE PRIMARY MYELOFIBROSIS PATIENTS
Authors: C. Potre, E. Borsi, M. Samfireag, M. Pescaru, O. Potre
Journal: HemaSphere (2019)

Background: Primary myelofibrosis (PMF) is a Philadelphia negative myeloproliferativ neoplasm characterized by a clonal myeloid expansion which determines progressive bone marrow fibrosis resulting in inefficient hematopoiesis. Diagnosis is based both on bone marrow morphology but also clinical aspects. There were described several mutations such as those in JAK2 V617F, MPL exon 10 and CALR exon 9 indel genes in aproximately 90% of the patients while the rest of 10% were so-called triple negative. Aims: To evaluate survival and prognosis in triple negative PMF patients. Methods: In this retrospective study, 58 patients diagnosed with PMF were enrolled from January 2014 to December 2018. Data were analyzed with SPSS 24. Results: The median age was 58 years. The male to female ratio was 3:1. Of the total 58 patients studied, 30 (51,72%) carried JAK2 (V617F), 14 (24,14%) showed positivity for CALR exon 9 indel, 4 (6,9%) had MPL (exon 10) mutation and 10 (17,24%) were so-called triple negative PMF. Median overall survival was 3,8 years in CALR mutant patients, 2,1 years in those presenting mutation in JAK2 gene, 2,3 years in MPL mutant patients and 1,6 years in triple negative patients. An analysis of the frequency of blast transformation at 1 year, revealed that it was identifyied in 71% of triple negative patients, 22% of JAK2 mutant patients and in 3% of both CALR and MPL mutant patients. Summary/Conclusion: This study reveals the importance of genetic analysis not only for diagnosing PMF but also for risk stratifying, prognos estimation and furthermore treatment choice. Triple negative PMF patients had a higher incidence of blast transformation compared with those presenting mutations.