tbuckley/cabot-search huggingface dataset:
PB1849 WHEN DO WE HAVE TO SUSPECT AND DIAGNOSE VON WILLEBRAND DISEASE?
Authors: S.Y. Hyun, K.S. Lee
Journal: HemaSphere (2019)

Background: Although von Willebrand disease (vWD) is the most common hereditary coagulation disorder, most of patients do not pay attention to their daily lives. While it is easy to treat already diagnosed vWD patients, it is also a characteristic of the disease that it is not easy to suspect and diagnose. The patient does not tell the doctor easy bruise as a major symptom because he (or she) does not know that this may have been caused by coagulation disease. It is very important to ask the patient whether he suffers from ’easy bruise or intractable nosebleed?’, ’ever suffered from poor stop‐bleeding on the injection site?’ or ’a family history of bleeding disorders?’ to determine the pressure time (10 minutes or more) to stop the injection site bleeding in cases of invasive procedure such as vaccination, blood collection or injection even when the patient is diagnosed and treated with other diseases. Menorrhagia or hypermenorrhea, delivery history and family history of coagulation disorder is hard to get medical history without specially asking. The reason why we are difficult to suspect and diagnose vWD: Many think easy bruise is not a disease. No one considered a repeat intractable nosebleed after stop as a result of basically coagulation defect. It seems to accept menorrhagia or hypermenorrhea as a mother's similarity and to solve only by gynecological treatment. Most doctors fail to treat iron deficient anemia because they do not pay attention for etiology. Do not recognize repeat test may be necessary because exercise and stress will make false positive result of vWF. Aims: Objective of this study was to examine the icidence and clinical features of VWD among the patients with easy bruising in the setting of primary care clinic. Methods: The screening test and the primary specific test for vWD (FVIIIc, vWF:RiCoF and vWF:Ag) and iron deficiency anemia (IDA) were done in 182 patients with bleeding symptoms (menorrhagia, easy bruising, etc.) among the patients who visited one private physician's clinic (Han's Clinic) for 4.5 years. Results: Twenty‐one patients were confirmed as vWD (vWF:RCo or vWF:Ag value was less than 30 or vWF:RCo/vWF:Ag &lt; 0.6) and 23 had vWF values less than 50. All except two were female. Median age was 34.7 (13‐71) years. Six of 21 patients had a family history. Most of them had iron‐deficiency anemia of moderate to severe. The main symptom was easy bruise in 16, anemia in 10, menorrhagia in 7, hypermenorrhea in 5, easy epistaxis in 2 and dizziness in 1. Iron deficiency anemia was confirmed in 8 of 21 patients. Four patients received prophylactic therapy with Minirin® effectively and 1 had treated with Immunate® for tooth extraction and 50 days’ menstruation. The menstrual period lasting for one month was reduced to normal with DDAVP inhalation and vWF infusion could stop bleeding soon after tooth extraction. Summary/Conclusion: Because accidents or emergency surgery can happen in life time to anyone, early suspicion and diagnosis will save life and reduce sequelae.
SAT0499 ORAL MICROBIOME IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITISIN RELATION TO DISEASE STATUS, TEMPOROMANDIBULAR JOINT ARTHRITIS AND MEDICATION: A NORWEGIAN 2-YEAR PROSPECTIVE STUDY
Authors: Paula Frid, Josefine Halbig, Divyashri Baraniya, Veronika Rypdal, Nils Thomas Songstad, Annika Rosen, Johanna Rykke Berstad, Berit Flato, Tsute Chen, Nezar Noor Al-Hebshi, Ellen Nordal, Mohammed Al-Haroni
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, with an annual incidence of 1-2 per 1000 children. The temporomandibular joint (TMJ) is involved in 40-70%. The human microbiome might be a potential contributing factor to the development of JIA. <h3>Objectives:</h3> To describe the oral salivary microbiome in children with JIA and relate this to disease activity, TMJ arthritis, and systemic medications. <h3>Methods:</h3> 93 children; JIA (n=59), Healthy (n=34) were recruited. Demographics, disease activity, presence of TMJ-arthritis and type of medication was collected in this Norwegian prospective study (www.norjia.com). 116 saliva samples were analyzed using Next Generation Sequencing, V1-V3 region of the 16S rRNA gene, coupled with BLASTn-based, species-level taxonomy assignment algorithm. Downstream bioinformatics analysis was performed with QIIME and LEfSe. <h3>Results:</h3> Mean age for healthy group (n=34; 27 females) is 12.3 ±3.0 years while for the JIA group (n=59; 43 females) the mean age is 12.6±2.7 years. A total of 541 bacterial species belonging to 111 genus and 10 phyla were identified, with Prevotella, Streptococcus, Actinomyces, Rothia Haemophilus and Veillonella accounting for the bulk of the average microbiome. There were no significant difference between JIA and healthy subjects in species richness and alpha diversity. However, differential abundance analysis revealed genera TM7-G1, Solobacterium and Mogibacterium to be associated with JIA, while Haemophilus and Lactococcus to be overabundant in healthy subjects. <h3>Conclusion:</h3> It seems that taxa associated with chronic inflammation were found to be enriched in the saliva of JIA patients. <h3>References</h3> [1] Frid P, Nordal E, Bovis F, Giancane G, Larheim TA, Rygg M, et al. Temporomandibular Joint Involvement in Association With Quality of Life, Disability, and High Disease Activity in Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken). 2017;69:677-86. <h3>Disclosure of Interests:</h3> None declared
Radiosensitization by Histone H3 Demethylase Inhibition in Diffuse Intrinsic Pontine Glioma
Authors: Hiroaki Katagi, Nundia Louis, Dusten Unruh, Takahiro Sasaki, Xingyao He, Ali Zhang, Quanhong Ma, Andrea Piunti, Yosuke Shimazu, Jonathan B. Lamano, Angel M. Carcaboso, Xiao Tian, Andrei Seluanov, Vera Gorbunova, Kathryn L. Laurie, Akihide Kondo, Nitin R. Wadhwani, Rishi Lulla, Stewart Goldman, Sriram Venneti, Oren J. Becher, Lihua Zou, Ali Shilatifard, Rintaro Hashizume
Journal: Clinical Cancer Research (2019)

Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing RT. No further clinical benefit has been achieved using alternative radiation strategies. Here, we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG.Experimental Design: We evaluated the effects of GSK-J4 on genes associated with DNA double-strand break (DSB) repair in DIPG cells by RNA sequence, ATAC sequence, and quantitative real-time PCR. Radiation-induced DNA DSB repair was analyzed by immunocytochemistry of DSB markers γH2AX and 53BP1, DNA-repair assay, and cell-cycle distribution. Clonogenic survival assay was used to determine the effect of GSK-J4 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and GSK-J4 was evaluated in patient-derived DIPG xenografts.GSK-J4 significantly reduced the expression of DNA DSB repair genes and DNA accessibility in DIPG cells. GSK-J4 sustained high levels of γH2AX and 53BP1 in irradiated DIPG cells, thereby inhibiting DNA DSB repair through homologous recombination pathway. GSK-J4 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and GSK-J4 compared with either monotherapy.Together, these results highlight GSK-J4 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.
S1614 CHROMOSOMAL ABNORMALITIES DETERMINE OUTCOME IN NPM1MUT/FLT3-ITDNEG/LOW ACUTE MYELOID LEUKEMIA
Authors: L. Angenendt, C. Röllig, P. Montesinos, D. Martínez-Cuadrón, E. Barragan, R. García, C. Botella, P. Martínez, F. Ravandi, T. Kadia, H.M. Kantarjian, J. Cortes, G. Juliusson, V. Lazarevic, M. Höglund, S. Lehmann, C. Recher, A. Pigneux, S. Bertoli, P.-Y. Dumas, H. Dombret, C. Preudhomme, J.-B. Micol, C. Terré, Z. Ráčil, J. Novák, P. Žák, A.H. Wei, I.S. Tiong, M. Wall, E. Estey, C. Shaw, R. Exeler, L. Wagenführ, F. Stölzel, C. Thiede, M. Stelljes, G. Lenz, J.-H. Mikesch, H. Serve, G. Ehninger, W.E. Berdel, M. Kramer, U. Krug, C. Schliemann
Journal: HemaSphere (2019)

Background: Nucleophosmin 1 (NPM1) mutations confer a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms related tyrosine kinase 3 gene (FLT3) with a high allelic ratio is absent (FLT3-ITDneg/low). The prognostic impact is considered to be independent of the karyotype, most influentially in the most recent 2017 ELN genetic risk classification. Here we investigate the validity of this assumption. Aims: This study investigates the prognostic impact of concomitant cytogenetic abnormalities in NPM1mut/FLT3-ITDneg/low AML. Methods: We analyzed the impact of karyotype on outcome in intensively treated patients with NPM1mut/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers. NPM1wt/FLT3-ITDneg/low AML patients with adverse cytogenetic abnormalities from the same cohorts served as comparator for adverse risk. Results: We identified 2426 patients with NPM1mut/FLT3-ITDneg/low AML. 2000 (82.4%) of these had a normal and 426 (17.6%) had an abnormal karyotype, including 329 (13.6%) patients with karyotype abnormalities of intermediate risk and 83 (3.4%) patients with karyotype abnormalities of adverse risk. In patients with NPM1mut/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission (CR) rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .0001), inferior overall (5-year OS, 52.4%, 44.8%, 19.5%; P < .0001) and event-free survival (5-year EFS, 40.5%, 35.8%, 18.0%; P < .0001), and a higher cumulative incidence of relapse (5-year CIR, 43.6%, 44.2%, 51.9%; P = .0012). Cytogenetic risk remained independently associated with all endpoints in multivariable mixed-effects regression analyses adjusted for known clinicopathological risk factors (P < .0001 for all endpoints). In patients with adverse risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome. Summary/Conclusion: This international collaborative study reveals that cytogenetic abnormalities are important determinants of outcome in NPM1mut/FLT3-ITDneg/low AML. Most importantly, NPM1 mutated patients with the FLT3-ITDneg/low genotype and adverse risk cytogenetics share the same unfavorable prognosis as their NPM1 wildtype counterparts and should be classified accordingly.
Abstract P351: Remnant Cholesterol and Cardiovascular Disease Outcomes in Chronic Kidney Transplant Recipients
Authors: Basma Merhi, Theresa Shireman, Paul Jacques, Todd Pesavento, Joseph Kim, Myra Carpenter, John Kusek, Andrew Bostom
Journal: Circulation (2017)

Remnant cholesterol (RC) is the cholesterol content of circulating triglyceride-rich lipoproteins. Studies employing a simple calculation of RC from routine lipid/lipoprotein measures have demonstrated associations between RC levels and cardiovascular disease (CVD) outcomes in both observational study, and lipid lowering clinical trial cohorts. There are no published data evaluating the potential relationship between remnant cholesterol and CVD in chronic kidney transplant recipients [KTRs], a population with excess risk for fatal and non-fatal CVD. RC was calculated, using non-fasting plasma samples, as total cholesterol - [HDL cholesterol + LDL cholesterol] in n=3002 FAVORIT trial [NCT00064753] participants at randomization (mean 37.6, standard deviation ± 21.3, range 4-230 mg/dl). During a median follow-up of 4.0-years, the cohort experienced n=419 CVD outcomes [myocardial infarction, stroke, resuscitated sudden death, CVD death, and CVD procedural events, pooled]. Multivariable logistic regression modeling revealed that each 10 mg/dl increase of RC conferred a 16.4% increase [95% CI, 3.6-30.8%] in CVD risk adjusted for age, baseline CVD, diabetes, smoking, race, sex, body-mass index, LDL, HDL, natural log triglycerides, estimated glomerular filtration rate, natural log urinary albumin/creatinine, type of kidney graft, graft vintage, and the use of calcineurin inhibitors, steroids, or lipid lowering drugs. Given the residual risk for CVD after recommended LDL levels are achieved, these data suggest that interventions [i.e., such as eicosapentaenoic acid ethyl ester, which can lower RC by ~25-30%; Atherosclerosis 2016; 253: 81-87] targeting elevated RC concentrations in KTRs, merit consideration.
AB0794 PATIENTS GENOTYPE AND OA TREATMENT EFFICACY
Authors: Liudmyla Smolina, Liudmyla Khimion, Olexandr Burianov, Nataliia Kicha, Tetiana Sytiuk, Taras Omelchenko
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> it is known that some genes (FDPS, LCT, VDR) which determine the calcium, vitamin D and lactate metabolism may have impact on osteoarthritis (OA) development and course, and thus, has a possible influence on OA treatment efficacy. <h3>Objectives:</h3> To determine the influence of genetic factors (genotyping of FDPS, LCT, VDR) on the efficacy of standard and modified treatment (with use of the platelet autologous plasma (PAP) in the early stages of knee OA. <h3>Methods:</h3> WOMAC index and the frequency of genotype variants for the FDPS, LCT, and VDR genes were studied in 96 patients (57 women, 38 men, 41.7 ± 1.2 years old) with primary knee OA (X-ray stage I-II). All patients had OA exacerbation with no clinical evidence of synovitis. Enrolled patients were divided into 2 groups: the first group consisted of 49 patients (27 women, 22 men, mean age 41.7 ± 1.2 years) who agreed to receive standard OA treatment (NSAID, exercises, orthopedic devises – as needed) and 3 intra-articular PAP injections (2 courses in 12 month, plasma volume 12-15ml/course, total platelet count per injection 1260,24 ± 22,1x10<sup>9</sup>). The second group - 47 patients with OA who received standard treatment. Both groups were comparable by age, gender, body mass index and initial WOMAC. Genetic parameters and its influence on OA course and treatment efficacy was analyzed during 12 months. <h3>Results:</h3> The earliest age (37.2 ± 2.01 years) of clinical manifestation of knee OA was connected to homozygous genotype variants: LCT (relative risk 6.3:1), FDPS (relative risk 6.5:1) and VDR (relative risk 6.8:1). The best positive WOMAC changes was determined in patients with the CC genotype of LCT both in first and second groups. The WOMAC changes showed lower treatment efficacy in patients with CC genotype of FDPS and VDR in both groups, but results of patients who received PAP were better and their remission was longer (in 1.7 times) than in the standard treatment group. Conclusion: age of knee OA clinical manifestation and the treatment efficacy (both standard and with the use of platelet autologous plasma) has genetic predisposition. <h3>Disclosure of interests:</h3> None declared
SAT0117 THE IMPACT OF DIFFERENT CRITERIA SETS ON EARLY REMISSION AND IDENTIFYING ITS PREDICTORS IN RHEUMATOID ARTHRITIS: RESULTS FROM AN OBSERVATIONAL COHORT (2009–2018)
Authors: Wenhui Xie, Xiaoying Sun, Zhuoli Zhang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Currently, with increased awareness of early diagnosis and intervention and the identified association of early remission with a better clinical outcome in patients with rheumatoid arthritis (RA), shorter time to remission appears to be a more attractive goal. There are several studies reported the prevalence of early remission, no study so far has demonstrated the issue in Chinese population. Moreover, further investigative studies need to be performed due to limited and conflicting predictors of early remission in previous studies. <h3>Objectives</h3> To assess rates of early remission and investigate the concordance across different remission definitions, and to identify predictors of early remission in Chinese patients with RA. <h3>Methods</h3> For this study, clinical records were retrospectively reviewed for RA patients at rheumatologic clinic in Peking University First Hospital from 2009 to 2018. Disease activity and remission were determined according to DAS28-ESR, CDAI, SDAI, and Boolean criteria. Early remission was defined as time to remission ≤ 6 months. A secondary definition evaluated early remission as ≤ 3 months. Logistic-regression analyses were performed to identify determinants of early remission. <h3>Results</h3> 869 consecutive patients contributing 8,640 clinic visits were studied. Early remission rates were respectively 42.0% (DAS28-ESR), 25.0% (CDAI), 29.4% (SDAI), and 26.1% (Boolean). Notably, patients achieving remission within 6 months more frequently attained sustained remission by contrast to those not achieving early remission (68.7-75.1% vs. 31.2-33.1%, P&lt;0.0001). Further logistic-regression analyses revealed male (OR=1.42-1.74, p&lt;0.05), early RA (OR=1.64-2.22, p&lt;0.05), as well as initial hydroxycloroquine treatment (OR=1.41-1.81, p&lt;0.05) were independently associated higher probability of early remission, as demonstrated by nearly all definitions, while a higher baseline disease activity (DAS28-ESR, CDAI, and SDAI) lowered the possibility of early remission in corresponding remission indices. However, the significant associations of treatment-naïve, serological features with early remission were not confirmed. <h3>Conclusion</h3> Early remission was strongly associated with sustained remission, however infrequently achievable in real-life practice. Male, early RA, a low baseline disease activity, and initial hydroxycloroquine treatment were stable independent predictors of early remission. <h3>Disclosure of Interests</h3> None declared
AB0895 EFICACY AND SAFETY OF ALLOPURINOL WHILE TITRATING HYPERURICAEMIA IN GOUTY PATIENTS
Authors: Mirjana Zlatkovic-Svenda, Marija Radak-Perovic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> according to EULAR 2016 recommendations (1), a drug of choice for gout treatment in patients with normal kidney function is Allopurinol, which should be started at 100 mg daily and titrated up to 600-900 mg daily (raised up for 100 mg every 2-4 weeks) in order to reach the target serum uric acid (SUA) level of &lt; 6 mg/dL (360 µmol/L). However, this advice is mostly not followed in daily clinical practice, mainly because of the adverse events precaution. <h3>Objectives</h3> to monitor the eficacy and safety of different dose regimens of Allopurinol while treating hyperuricaemia in gouty patients. <h3>Methods</h3> in a prospective study gouty patients were included consequetly, as they have entered the Rheumatology Institute in Belgrade, classified as either chronic or newly-diagnosed. Allopurinol was titrated monthly up to the recommended SUA level or the severe adverse events occurence (following hypersensitive drug reactions, liver and kidney function tests and the number of blood cells). Patients were followed-up for 6 months. <h3>Results</h3> study enrolled 61 patients (92,1% male) aged 59,2 (9,6) years. Their mean (SD) SUA level was 454,8 (99,3), 362,7 (60,9) and 388,2 (74,4) µmol/L at 1,2 or 3 months of therapy, respectively. At three months of therapy, target SUA level was reached by 45 (73,8%) of patients treated with Allopurinol up to 300 mg daily. For non-responders, Allopurinol was raised to 400-600 mg daily and additional 12 (19,6%) of patients reached the target SUA level (mean 353,6 (36,2) µmol/L), whereas only 6,6% of patients did not reach the therapeutic goal. Gouty flares were identified in 11/61 (18%) of patients, gastrointestinal symptoms were reported by 6/61 (9,8%), 5/61 pts (8,2%) have evolved hepatotoxicity with minor liver function abnormalities and Allopurinol induced mild skin rash was seen in 7/61 (11%) of patients. All adverse events were mild and the therapy was not changed. <h3>Conclusion</h3> Allopurinol increasing dose regime was efficient in hyperuricaemia treatment, and the target goal was reached by 93,4% of patients. All adverse reactions were mild and did not influence dose regimen at the end of the 6 months period of follow-up. <h3>Reference</h3> [1] Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J,Coyfish M, Guillo S, Jansen TL, Janssens H, Lioté F, Mallen C, Nuki G, Perez-Ruiz F, Pimentao J, Punzi L, Pywell T, So A, Tausche AK, Uhlig T, Zavada J, Zhang W, Tubach F, Bardin T. 2016updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017 Jan;76(1):29-42 <h3>Disclosure of Interests</h3> None declared
THU0709-HPR PERSONS WITH POLYMYOSITIS AND DERMATOMYOSITIS EXPERIENCE REDUCED WORK ABILITY AND QUALITY OF LIFE
Authors: Karin Åström, Malin Regardt
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> A recent study have described that persons with Polymyositis (PM) and Dermatomyositis (DM) experience reduced work ability (1). Information about whether the reduced work ability affect quality of life is lacking. <h3>Objectives:</h3> To describe self-rated work ability with two different assessment and quality of life in persons with PM and DM. To investigate correlations between self-rated work ability and quality of life <h3>Methods:</h3> Participants were identified through the Swedish Myositis Network registry (SweMyoNet). Of 78 possible participants, 48 agreed to participate in this study. The median (IQR) age were 57 (45-61) years with a median disease duration of 6 (2-14) years. Fifty-three percent of the participants were women. Seventy-seven percent were working, and the remaining were on sick-leave. Self-rated work ability was measured by the questionnaire Work Ability Index (WAI) and the Work Ability Score (WAS) which is a single item question. Quality of life by the SF-36. <h3>Results:</h3> Self-rated work ability measured by WAI in persons with PM and DM varied between poor work ability and good work ability. The median value of the group was 34 which indicates less good work ability. Self-rated work ability measured by WAS varied between poor work ability and good work ability. The median of the total group indicates less good work ability. There was a strong correlation between self-rated work ability measured by WAI and WAS (rs 0,879 p=0,01). Quality of life measured by SF-36 were rated lower in persons with PM and DM when compared to the general population in dimensions; Physical Function, Role-Physical, General Health, Vitality and Social function (p≤0.02). There were moderate to high correlations between self-rated work ability measured by both WAI and WAS, and all dimensions of SF-36 (p&lt;0.01) <h3>Conclusion:</h3> Persons with PM and DM self-rated their work ability as poor and the quality of life were significantly reduced when compared to the general population. The measures WAI and WAS correlates highly with each other and revealed comparable results indicating that WAS may work as well as WAI as a screening tool to identify reduced work ability. The WAS may also be more feasible with just one single question to use in clinical practice. Our results indicate the importance to measure self-rated work ability in persons with PM and DM in clinical practice. <h3>References:</h3> [1] M. Regardt, I. E. Lundberg, et al. Work ability in patients with polymyositis and dermatomyositis: an explorative and descriptive study.Accepted for publication Work 2015;53:265-77. <h3>Disclosure of Interests:</h3> None declared