tbuckley/cabot-search huggingface dataset:
THU0012 HLA-DBR1 alleles profile in patients with rheumatoid arthritis: relation to disease susceptibility and severity
Authors: A Paradowska-Gorycka, B Stypinska, E Haladyj, K Romanowska-Prochnicka, A Pawlik, M Olesinska
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a complex, chronic autoimmune disease (AID) that affects approximately 0.5%–1% of the population worldwide. RA is considered to be complex diseases of unknown etiology, where the environmental, immunological and genetic factors contributed to susceptibility and severity of the disease. Since the first evidence suggesting the involvement of human leukocyte antigens (HLAs) in RA was reported in 1969, the HLA region have been at the center of genetic studies of RA. <h3>Objectives</h3> We undertook this study to elucidate the association between HLA-DRB1 alleles profile and susceptibility to and severity of RA in a Polish population. <h3>Methods</h3> We analyzed the data on a total of 472 RA patients in whom HLA-DRB1 allele genotyping had been performed. DNA sequences for exon 2 of the DRB1 locus were typed using polymerase chain reaction-sequence-based typing (PCR-SBT). <h3>Results</h3> Identification of the variants potentially associated with risk and protection was carried out by comparison to the DKMS Polish Bone Marrow Donor Registry (41306 alleles). A significant increase in the frequency of the HLA-DRB1*15:01 (p=0.001), DRB1*04 (p&lt;0.0001), DRB1*01:01 (p&lt;0.0001),DRB1*10:01 (p=0.003) and *09:01 (p&lt;0.0001) were identified in patients with RA and showed strong association with the disease susceptibility. Furthermore, the HLA-DRB1*07:01 allele was found to be protective (p&lt;0.0001) in our RA patients. In the RA patients with HLA-DRB1*52:01 allele the mean value of PLT (p=0.03) and organ symptoms (p=0.02) were more frequent than in RA patients without this allele. In RA patients with DRB1*01:01, DRB*04 as well as DRB1*15:01 alleles the number of tender joints (p=0.03), diabetes (p=0.03) and renal failure) p=0.03) were observed less frequently compared with RA patients without these alleles. We also observed that in RA patients with DRB1*10:01 the VAS score was higher than in RA patients without this allele. No association was detect between the HLA-DRB1*07:01 and DRB1*09:01 and disease activity and laboratory parameters among RA patients. <h3>Conclusions</h3> Current finding indicated that HLA-DRB1*15:01 DRB1*04, DRB1*01:01 and DRB1*10:01 alleles may be associated with susceptibility to as well as severity of RA. <h3>Disclosure of Interest</h3> None declared
The new editor greets you
Authors: Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2017)

Video 1 






It is a great privilege and honour to assume the position of editor of the Annals of the Rheumatic Diseases–The EULAR Journal and I am very grateful to the selection committee consisting of members from both constituencies for granting me this opportunity.

Even bigger is the challenge to take on this position as a successor of Professor Tore Kvien. During the 9 years of his editorship, Professor Kvien has continued the work of the founding Editor after initiation of the collaboration between BMJ and EULAR , Professor Leo van der Putte, and has furthered the impact of The EULAR Journal with prudent and far-sighted editorial decisions. These have allowed the Annals to become the leading journal in the field of rheumatology. While a success like this is impossible without receiving good manuscript and especially an excellent team of associate editors, editorial board members and reviewers, Tore’s visions and leadership were instrumental for this development. Thank you very much, Tore!

The accomplishments of the Annals during the 18 years since it became …
OP0117 Bone marrow oedema in sacroiliac joints of young athletes shows most frequently in the posterior inferior ilium
Authors: U Weber, AG Jurik, A Zejden, E Larsen, SH Jørgensen, K Rufibach, C Schioldan, S Schmidt-Olsen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Low grade bone marrow oedema (BMO) was reported in the sacroiliac joints (SIJ) of up to 25% of healthy individuals and mechanical back pain patients, challenging the imaging discrimination from early spondyloarthritis (SpA) [1]. Potential explanations range from mechanical stress lesions to vascular signals and anatomical SIJ variants. <h3>Objectives</h3> To determine BMO frequency and anatomical distribution in 8 SIJ regions in hobby and professional athletes. <h3>Methods</h3> The sample consisted of 2 cohorts of 20 healthy hobby runners (HR) before and after running and 22 professional ice hockey players (IP) from the Danish premier league: HR/IP 40%/100% men; mean age (SD) 27.2 (5.4)/25.9 (4.6) years; mean BMI (SD) 22.6 (1.5)/25.7 (1.6) kg/m<sup>2</sup>. Semicoronal MRI scans of the SIJ with T1SE and STIR sequences were obtained in HR before and 24 hours after a running competition over 6.2 kilometers (mean duration 35.4 minutes, mean speed 10.4 km/h), and in IP during the competitive season. The scans were assessed for BMO independently by 3 blinded readers (AGJ, AZ, UW) according to the quadrant based MORPHO module (www.carearthritis.com). Paired images of HR were read blinded to timepoint. 7 MRI scans (2 paired images) of SpA patients under TNF treatment served to mask readers. A pre-test reader calibration used MRI scans from 11 patients with active sacroiliitis and 9 healthy volunteers. Reader agreement was assessed by ICC (3, 1). Descriptive analysis comprised mean frequency of SIJ quadrants with BMO and distribution of BMO quadrants in 8 anatomical SIJ regions: upper/lower ilium and sacrum, subdivided in anterior and posterior slices, as concordantly recorded by the majority (≥2/3) of readers. <h3>Results</h3> Agreement among 3 readers for SIJ BMO was excellent in calibration (ICC 0.93) and moderate in athletes (ICC 0.59) due to low frequency of BMO. The mean number (SD) of SIJ quadrants showing BMO was 3.1 (4.2)/3.1 (4.5) in HR before/after running, and 3.6 (3.0) in IP. The posterior inferior ilium was the single most affected region, followed by the upper anterior sacrum, consistently across 2 cohorts of athletes. <h3>Conclusions</h3> In hobby and professional athletes, BMO showed on average in 3–4 SIJ quadrants. The posterior lower ilium was the SIJ region most frequently affected by BMO. These findings in healthy controls may help refine thresholds for a positive SIJ MRI in early SpA. <h3>References</h3> Weber U et al. Curr Rheumatol Rep 2016;18:58. <h3>Disclosure of Interest</h3> None declared
THU0673 The european consensus finding study group (ECFSG) helps characterizing new tentative reference standards for autoantibody measurement
Authors: J Rönnelid, C Dahle, M Blüthner, E Feist, C Dolman, SJ Thorpe, E Monogioudi, I Zegers, PL Meroni, D Hamann
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Since 1988, the European Consensus Finding Study Group on autoantibodies in rheumatic diseases (ECFSG), also known as the EULAR autoantibody study group, has been distributing sera with unspecified antibodies to European laboratories (presently n=43) for evaluation of different autoantibody measurement techniques in a clinical context. Use of reference materials helps to align test results by adopting internationally used measurement units, but reference materials are missing for many autoantibody specificities. <h3>Objectives</h3> Recently the scope for ECFSG was expanded to also include unbiased autoantibody characterization of serum/plasma specimens planned to constitute raw material for production of future autoantibody reference materials. <h3>Methods</h3> Four samples were included to be evaluated as future tentative international reference materials for four different autoantibody specificities: double stranded/native DNA (dsDNA, evaluated in 2013/14), IgG anti-b2GP1, proteinase 3 (PR3) and myeloperoxidase (MPO, evaluated in 2015/16). The samples were included “blind”, and evaluated broadly for multiple autoantibody specificities by participating laboratories. <h3>Results</h3> All or almost all participating laboratories detected the target specificities, and all four samples showed restricted autoantibody specificities related to the target specificity. Anti-dsDNA was detected by all laboratories using <i>Crithidia luciliae</i>, ELISA/EIA, FARR assay or ALBIA and all labs reported a homogenous ANA pattern. Other specificities were restricted to histones, nucleosomes and anti-Ku. All laboratories but one detected IgG anti-b2GP1 and IgG anti-cardiolipin, mostly in high levels, in the tentative IgG anti-b2GP1 reference standard, whereas corresponding IgA and IgM antibodies were absent. All laboratories detected anti-MPO, mostly monospecific and in high levels together with P-ANCA pattern in the anti-MPO reagent. Anti-PR3 and C-ANCA pattern, mostly in high levels/titers were detected by all laboratories in the tentative anti-PR3 reagent, irrespective of method used. <h3>Conclusions</h3> The expanded scope of ECFSG has enabled broad characterization of new tentative autoantibody reference standards. The anti-dsDNA specimen has been processed by the National Institute for Biological Standards and Control (NIBSC) for consideration as the 2nd WHO anti-dsDNA reference standard. The other materials are basis for certified reference material for IgG anti-myeloperoxidase (ERM-DA476/IFCC), and the candidate reference materials for IgG anti-proteinase 3 (in certification) and for IgG anti-b2PG1 (in evaluation) from the Joint Research Centre. <h3>Disclosure of Interest</h3> None declared
Novel small molecule inhibitors for pancreatic cancer
Authors: Junan Li, Jiuxiang Zhu, Ching-Shih Chen, W. Scott Melvin, Peter Muscarella
Journal: Cancer Research (2005)

665  Pancreatic cancer is the fifth most common cancer causing death in the United States. Surgical resection remains the only hope for cure, but the overall 5-year survival rates remain low at 3%. Novel therapeutic strategies are desperately needed. One possibility is the application of small molecule inhibitors (SMI). Disadvantages of currently available SMIs include tumor resistance, poor specificity, potential toxicity, and poor bioavailability. Through structural optimization, we have synthesized a group of novel SMIs that retain potency for inhibiting the growth of different cancer cell lines. Here we evaluated potential efficacy of these agents for human pancreatic cancer therapy using in vitro studies. Human pancreatic cancer cell lines AsPC-1, BxPC-3, MiaPaCa-2, and PANC-1 were incubated with varying concentrations of different agents, and cell viability was measured using an MTT assay. Of the four agents, OSU-0312, a PDK-1/Akt specific inhibitor derived from Celecoxib, demonstrated the highest potency and the lowest tumor cell resistance, suggesting that OSU-0312 may have translational relevance for pancreatic cancer therapy. 1GI50 is defined as the agent concentration which decreases the cell viability to 50%. 2GI50 is out of the tested concentration range of the agent, which suggests the agent is not potent or less potent in this cell line.
<i>In Silico</i> Modeling of Immunotherapy and Stroma-Targeting Therapies in Human Colorectal Cancer
Authors: Jakob Nikolas Kather, Jan Poleszczuk, Meggy Suarez-Carmona, Johannes Krisam, Pornpimol Charoentong, Nektarios A. Valous, Cleo-Aron Weis, Luca Tavernar, Florian Leiss, Esther Herpel, Fee Klupp, Alexis Ulrich, Martin Schneider, Alexander Marx, Dirk Jäger, Niels Halama
Journal: Cancer Research (2017)

Abstract Despite the fact that the local immunological microenvironment shapes the prognosis of colorectal cancer, immunotherapy has shown no benefit for the vast majority of colorectal cancer patients. A better understanding of the complex immunological interplay within the microenvironment is required. In this study, we utilized wet lab migration experiments and quantitative histological data of human colorectal cancer tissue samples (n = 20) including tumor cells, lymphocytes, stroma, and necrosis to generate a multiagent spatial model. The resulting data accurately reflected a wide range of situations of successful and failed immune surveillance. Validation of simulated tissue outcomes on an independent set of human colorectal cancer specimens (n = 37) revealed the model recapitulated the spatial layout typically found in human tumors. Stroma slowed down tumor growth in a lymphocyte-deprived environment but promoted immune escape in a lymphocyte-enriched environment. A subgroup of tumors with less stroma and high numbers of immune cells showed high rates of tumor control. These findings were validated using data from colorectal cancer patients (n = 261). Low-density stroma and high lymphocyte levels showed increased overall survival (hazard ratio 0.322, P = 0.0219) as compared with high stroma and high lymphocyte levels. To guide immunotherapy in colorectal cancer, simulation of immunotherapy in preestablished tumors showed that a complex landscape with optimal stroma permeabilization and immune cell activation is able to markedly increase therapy response in silico. These results can help guide the rational design of complex therapeutic interventions, which target the colorectal cancer microenvironment. Cancer Res; 77(22); 6442–52. ©2017 AACR.
THU0611 Long-term follow-up of 269 children born to mothers with systemic autoimmune diseases: a national survey from 24 rheumatology centers
Authors: C Nalli, L Andreoli, C Carini, M Rodrigues, F Dall'Ara, MG Lazzaroni, E Bartoloni-Bocci, CB Chighizola, C Campochiaro, P Conigliaro, A Corrado, S D'Angelo, M Favaro, E Generali, M Gerosa, M Larosa, M Meroni, M Padovan, G Pazzola, S Peccatori, I Prevete, V Ramoni, G Sebastiani, V Signorini, C Tani, M Trevisani, M Vadacca, E Vivaldelli, E Visalli, L Zuliani, A Afeltra, E Baldissera, A Brucato, FP Cantatore, R Caporali, M Cutolo, A Doria, R Foti, A Gabrielli, R Gerli, M Govoni, A Maier, N Malavolta, PL Meroni, G Minisola, CM Montecucco, M Mosca, I Olivieri, G Paolazzi, R Perricone, N Romeo, A Ruffatti, MG Sabbadini, C Salvarani, C Selmi, L Sinigaglia, A Tincani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatic diseases (RD) affect women during reproductive age. Children9s outcome is a major topic for counselling on family planning, but no large studies are available. <h3>Objectives</h3> We aimed at assessing the long-term health conditions of children born to mothers with RD through a self-reported questionnaire. <h3>Methods</h3> 24 Rheumatology Centers distributed the questionnaire (65 multiple choice and 12 open-answer questions) to consecutive women with RD attending their outpatient clinic during September 2015. Data were compared according to maternal diagnosis (MD) -chronic arthritis (CA) or connective tissue disease (CTD)- and to the timing of pregnancy (before or after MD of RD). <h3>Results</h3> The survey yielded data about 269 children born to 184 mothers (63 CA, 121 CTD). According to MD, children had a mean age of 17.1 (±9.6 SD) and 14.4 (±9.0 SD) years at the time of interview, and male children were 52/93 (56%) and 91/176 (52%), respectively. Twenty-nine children in the CA group (31.2%) and 64 in the CTDs group (36.4%) were born after MD of RD. Pre-term delivery (before 37 weeks) was observed in 48 cases (17.8%), mostly children born to mothers with CTD (37/48, 77%). Regarding school performance, 12 children (4.5%) repeated one year of school, in 7 cases for indolence, in 3 for learning disabilities (LD)/health problems (HP), in 2 for family problems. Eleven of these children were born before MD. Overall, 9 children (3.3%) were diagnosed with a LD and 53 children were affected by HP requiring either hospitalization or evaluation by a Specialist (Table). Three children (1%) were affected by autoimmune disease. <h3>Conclusions</h3> The long-term follow-up of children born to women with RD is reassuring of an outcome similar to that of the general pediatric population (GPP). Autoimmune diseases are not frequent. Problems seem to cluster in children born to CTD, especially after MD, with a higher frequency of LD (6.3% vs 2.5–3.5% of GPP), but no particular pattern of exposure to maternal autoantibodies nor drugs was observed. <h3>Acknowledgements</h3> Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients Associations and Participants to the survey <h3>Disclosure of Interest</h3> None declared
SAT0270 Ultrasonography of major salivary glands in juvenile sjÖgren's syndrome – preliminary findings in a multi-center study
Authors: DS Hammenfors, V Valim, B Bica, SG Pasoto, V Lilleby, JC Nieto-González, CA Silva, E Mossel, RM Pereira, H Bootsma, JG Brun, R Jonsson, MV Jonsson
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Juvenile Sjögren9s syndrome (jSS) is a rare, poorly defined and possibly underdiagnosed condition. There is little information on the use of major salivary gland ultrasonography (SGUS) in this patient-group. <h3>Objectives</h3> To characterize symptoms and clinical findings of jSS and to investigate SGUS as a diagnostic tool. <h3>Methods</h3> Sixty-four patients were recruited from Brazil (n=40), Norway (n=11), the Netherlands (n=8) and Spain (n=5). All patients had disease onset at the age of 18 or younger. Clinical examination and sialometry was performed in 60/64 patients. Additional clinical information was obtained from the medical records and through patient interview. SGUS of the parotid and submandibular glands was performed in all patients using linear high-frequency transducers (6–15 MHz), by an expert in SGUS. Glandular homogeneity and presence of hypoechogenic areas were evaluated and glands characterized as normal or SS-like. <h3>Results</h3> The female:male ratio was 6:1. Mean age at diagnosis was 12.1 years (range 4–18), with first symptoms occurring at 10.3 years (range 1–17). Time from onset of symptoms until diagnosis was 1.6 years (range -2–8 years). Subjective oral and ocular symptoms were reported in 70% and 64% patients, respectively. Reduced secretion of tears was detected in 41% patients, and hyposalivation in 31% patients. Minor salivary gland lip biopsy had been performed and focus score determined in 34 patients; 28 biopsies (82%) had focus score ≥1. Serologically, 92% were positive for ANA, 73% were anti-Ro/SSA+, 38% were anti-La/SSB+, and 41% were RF+. Salivary gland enlargement had been experienced by 53% of the patients; one patient had also experienced lacrimal gland enlargement. Systemic manifestations at some time-point, was registered in 66% of the patients. Systemic treatment at inclusion was registered in 67% of the patients; previous systemic treatment was registered in 83%. Diagnostic criteria for primary Sjögren9s syndrome (pSS) was fulfilled by 34/64 patients (53%) and 39/64 patients (61%), AECG criteria and ACR/EULAR criteria, respectively. SGUS revealed SS-like changes in 37/64 patients (59%); interestingly, SS-like findings were observed in 22/23 patients in the European cohort, compared to 15/40 patients in the Brazilian cohort. <h3>Conclusions</h3> Common symptoms and findings in jSS include dry mouth, systemic manifestations and salivary gland enlargement, followed by reduced tear secretion and hyposalivation. <h3>Disclosure of Interest</h3> None declared
A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy
Authors: Jeremie H. Estepp, Matthew P. Smeltzer, Guolian Kang, Chen Li, Winfred C. Wang, Christina Abrams, Banu Aygun, Russell E. Ware, Kerri Nottage, Jane S. Hankins
Journal: American Journal of Hematology (2017)

Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose-dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long-term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA. In 230 children, providing 610 patient-years of follow up, the mean attained HbF% at MTD was >20% for up to 4 years of follow-up. When HbF% values were ≤20%, children had twice the odds of hospitalization for any reason (P < .0001), including vaso-occlusive pain (P < .01) and acute chest syndrome (ACS) (P < .01), and more than four times the odds of admission for fever (P < .001). Thirty day readmission rates were not affected by HbF%. Neutropenia (ANC <1000 × 106 /L) was rare (2.3% of all laboratory monitoring), transient, and benign. Therefore, attaining HbF >20% was associated with fewer hospitalizations without significant toxicity. These data support the use of hydroxyurea in children, and suggest that the preferred dosing strategy is one that targets a HbF endpoint >20%.
FRI0744-HPR The effectiveness of the lower dose of laser treatment on knee osteoarthrİtİs
Authors: E Ekiz, K Capaci, M Korkmaz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> During knee osteoarthritis (OA) therapy; medications, physical therapy modalities, exercises and surgical procedures are used. In previous studies, the benefits of low level laser therapy (LLLT) for pain in the low back, shoulder, elbow, and hand have reported. <h3>Objectives</h3> In this study we aimed to investigate the effectiveness of LLLT on pain, functional status, and quality of life in patients with knee osteoarthritis. <h3>Methods</h3> Patients with Kellgren-Lawrence stage 2–3 knee osteoarthritis were enrolled. It was planned as a prospective, randomized and double-blind study. Group 1 received active laser therapy and group 2 placebo laser therapy. Patients have been provided active/placebo laser therapy for two weeks (5 days a week, a total of 10 sessions). Patients were evaluated before, immediately after and 1 or 3 months after treatment. Outcome measurements included pain intensity at rest and at movement on visual analog scale, knee function using Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scale, active/passive joint range of movement, quality of life using Short form 36 (SF-36), and 15-meter walking distance, painless walking distance. <h3>Results</h3> In this study, we observed improvements in knee pain, 15-meter walking distance, WOMAC pain, stiffness and function scores, Lequesne index, and SF-36 physical function and social function (p&lt;0.05) in active LLLT group. Also, significant improvements were detected in SF-36 physical role, mental health, vitality and emotional role parameters compared with placebo laser group (p&gt;0.05). <h3>Conclusions</h3> The present study demonstrated that LLLT is safe and effective upon pain and functional parameters on knee osteoarthritis. However, we think further long-term studies which will include more patients in order to determine the priority and effectiviness are required. <h3>Disclosure of Interest</h3> None declared