tbuckley/cabot-search huggingface dataset:
PS1576 ADENOSINE DIPHOSPHATE RECEPTOR GENE (P2Y12) SEQUENCE VARIANTS AMONG SWEDISH, PALESTINIAN AND CONGOLESE INDIVIDUALS
Authors: M. Asees, R. Abu Seir, C. Hesse, A. Reza
Journal: HemaSphere (2019)

Background: The P2Y 12 receptor plays a central role in platelet aggregation and thrombus formation. Recently, inter‐individual variations in platelet response of healthy untreated individuals were established which was explained by genetic variations in the P2Y 12 receptor gene. Several single nucleotide polymorphisms (SNPs) in the P2Y 12 receptor have been associated with increased platelet reactivity and risk of cardiovascular diseases. Aims: This study aimed to evaluate the pathological H2 haplotype (using G52T as a tag‐SNP) and 18C&gt;T polymorphisms in three different ethnic groups; Palestinians, Swedish and Congolese. in addition to that, to investigate the effect of H2 haplotype pn palatelt aggregation induced by ADP/TRAP agonists. Methods: The H2 haplotype and 18C&gt;T SNPs were determined in conveniently selected healthy individuals from different ethnic groups (n = 254). The whole exon‐3 of P2Y 12 was sequenced and analyzed by using ABI PRISM 310 Genetic Analyzer. The major and the minor allele frequencies of the P2Y12 SNPs were determined in the study population and the genetic differences between ethnic groups in P2Y 12 were elucidated. In addition, the frequency of the genotypes were calculated among the different ethnic groups. Results: In this study, five benign single nucleotide polymorphisms (SNPs) were genotyped and identified; 18C&gt;T, 36G&gt;T, 162G&gt;T, 546C&gt;T and 989A&gt;G. The overall frequencies of each SNP in the study population (n = 254) was 21.9, 10, 0.4, 0.6 and 0.4%, respectively. The frequency of H2 haplotype was among Swedish 23.6% (n = 55), Congolese 12.0% (n = 54) and Palestinian 4.1% (n = 145). There were significant differences in frequency of H2 haplotype and 18C&gt;T among the ethnic groups ( P &lt; 0.001). In regard to the pathological SNPs (767G&gt;A [p. Arg256Gln] and (793C&gt;T [Arg265Trp]) all of the study participants were negative. Summary/Conclusion: There are significant differences in the frequencies of the genetic variants of the P2Y 12 exon‐3 between the studied ethnic groups. Application of these findings may explain the variable platelet response in healthy individuals and in patient under thienopyridine compounds. Further studies should be performed to study the effect of the genetic variations effect on ADP or TRAP‐ induced platelet aggregation.
AB0596 ASSESMENT OF DAMAGE IN TAKAYASU ARTERITIS PATIENTS WITH VASCULITIS DAMAGE INDEX (VDI) AND TAKAYASU ARTERITIS DAMAGE SCORE (TADS)
Authors: Sema Kaymaz Tahra, Fatma Alibaz-Oner, Haner Direskeneli
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Evaluation of damage in patients with takayasu arteritis is important because of the mortality and morbidity burden caused by the disease. Damage can be associated with treatment or with the disease itself (1). <h3>Objectives:</h3> In this study we aimed to evaluate the damage in our Takayasu arteritis patients by using VDI and TADS scores. <h3>Methods:</h3> Takayasu arteritis patients fullfilling the ACR 1990 criteria and had &gt;3 months follow-up were enrolled in this study. TADS and VDI scores calculated at the end of the follow-up evaluated and compared. <h3>Results:</h3> 114 patients (F/M: 101/13) were included in the study. The mean age at diagnosis, median symptom duration at baseline visit and mean follow-up duration were 35.3±13.3 years, 12 (0-360) months and 76.9 ± 51.4 months respectively. Mean VDI score was 5.1±2.5 and mean TADS score was 7.9±3.5. At least one disease-related damage item was present in all of the patients for both VDI and TADS meanwhile ≥1 treatment-related damage item was established in 69 (66.1%) patients with VDI and 46(40.7%) patients with TADS scoring system. Median treatment related-item number was 1 (0-6) in VDI and 0(0-3) in TADS. This difference may be due to the lack of disease-related parameters such as diabetes, cataract, osteoporosis, avascular necrosis in TADS. The median number of disease-related items was higher in TADS scoring (4 items vs 8 items). TADS scores include more detailed and higher number of items under vascular intervention and pulse loss categories. Also bruit and systolic hypertension data is only available in TADS(Table1). There was no significant difference between patients with relapsing disease and patients with no relapses for both TADS and VDI scores. There was a weak corelation between VDI and cumulative steroid dose(p=0.002, r=0.32), and VDI-disease duration (p=0.001, r=0.29). A weak corelation between TADS and disease duration was established(p=0.04 r=0.19). No corelation was detected for TADS and cumulative steroid dose. <h3>Conclusion:</h3> In Takayasu arteritis, detecting the disease-related and treatment-related part of damage must be considered while monitoring the disease. VDI seems to be predominant evaluating the treatment-related damage. TADS provides more detailed information on disease-related damage. <h3>References</h3> [1] Omma A., Erer B., Karadag O.et al. (2017). Remarkable damage along with poor quality of life in Takayasu arteritis: cross-sectional results of a long-term followed-up multicentre cohort. Clin Exp Rheumatol., 35, 77-82. VDI: Vasculitis Damage Index TADS: Takayasu Arteritis Damage Score ENT: Eye-Nose-Throat '-' this item is not included in this scoring system '---' this item is categorized in another category in the scoring system mentioned <h3>Disclosure of Interests:</h3> None declared
AB0990 FINAL DIAGNOSIS OF THE PATIENTS WITH MUSCULOSKELETAL COMPLAINTS: PRELIMINARY RESULTS OF ONE-YEAR STUDY
Authors: Nuray Aktay Ayaz, Hafize Emine Sonmez, şerife Gül Karadağ, Ayşe Tanatar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Musculoskeletal (MS) complaints are one of the most common reason for administration to outpatient clinics. <h3>Objectives</h3> The study aimed to summarize the final diagnosis of the patients who suffered from musculoskeletal (MS) findings. <h3>Methods</h3> We prospectively evaluated the patients who were referred with the complaints of MS systems in a year period. <h3>Results</h3> A total of 940 patients with the complaint of musculoskeletal systems were examined. Among them, 577 patients suffered from arthralgia, 234 had arthritis, 39 had low-back pain, 26 had limping, and 64 had other symptoms such as myalgia, heel pain, hip and neck pain. A diagnosis of rheumatic disease was made in 430 of patients, while 510 had non-rheumatic conditions. Final rheumatological disease diagnoses were as follows: juvenile idiopathic arthritis (n=195), familial Mediterranean fever (n=101), reactive arthritis (n=46), acute rheumatic fever (n=39), toxic synovitis (n=17), psoriasis (n=8), Raynaud's phenomenon (n=6), chronic recurrent multifocal osteomyelitis (n=5), vasculitis (n=5), systemic lupus erythematosus (n=4), juvenile dermatomyositis (n=2) and juvenile scleroderma (n=1). Among patients with non-rheumatic conditions, most of them had vitamin D deficiency, infections, mechanic-orthopedic conditions, and growing pains. <h3>Conclusion</h3> Evaluation of a child presenting with MS findings requires a comprehensive, multidisciplinary, and systematic approach. As a busy pediatric rheumatology center, we demonstrated the final diagnosis of referred patients with MS symptoms and only less than half of the patients were diagnosed as a rheumatological condition. Whilst pediatric rheumatology centers are limited in number, our results put forth the need of formulating recommendations for clinicians in order to prevent unnecessary referrals <h3>References</h3> [1] Cavkaytar O, Duzova A, Tekşam O, et al. Final diagnosis of children and adolescents with musculoskeletal complaints. Minevra Pediatr. 2017; 69:50-58 [2] Hashkes PJ, Profile of a pediatric rheumatology practice in Israel, Clin Exp Rheumatol. 2003 Jan-Feb;21(1):123-8. <h3>Disclosure of Interests</h3> None declared
PS1432 3‐WEEKLY DARATUMUMAB‐IMID‐DEXAMETHASONE IS HIGHLY EFFICACIOUS, HENCE FINANCIALLY AFFORDABLE WITH ENORMOUS ECONOMIC IMPACT FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA IN LESS AFFLUENT COUNTRIES
Authors: C.S. Chim, V.K. C. Wong, Y.L. E. Au, Y.L. Kwong
Journal: HemaSphere (2019)

Background: Daratumumab (dara) with immunomodulatory agents (IMiD) and dexamethasone (dex) is highly effective in relapsed multiple myeloma (MM). The recommended schedule of dara is weekly for 8 doses, followed by 2‐weekly for 8 doses, and then every 4‐weekly thereafter. Given the high cost and the long half‐life as an antibody, a 3‐weekly dosing of dara was used together with IMiD/dexamethasone. Aims: Dara at 16 mg/kg was used every 3‐weekly with lenalidomide or pomalidomide. Patient achieving best response received single agent IMiD maintenance until disease progression. Methods: Fourteen relapsed MM patients were enrolled. One had received weekly dara from a private oncologist, hence was excluded from analysis. Thirteen patients at a median age of 63 years (range: 50–84 years) were studied. The median number of previous therapies was 2 (range: 1–5), with nine patients (69.2%) having undergone autologous stem cell transplantation. Three patients (23.1%) were refractory to bortezomib, seven patients (53.8%) to lenalidomide, and eight patients (61.5%) to last treatment. At relapse, two (15.4%) had high LDH, eight (61.5%) impaired renal function, and three (23.1%) extramedullary disease. Treatment was dara‐lenalidomide‐dex in six (46.2%), and dara‐pomalidomide‐dex in seven (53.8%). Results: Responses after four cycles included CR in 5 patients (38.5%), VGPR in five patients (38.5%), and PR in three patients (23.1%). After a median of four dara infusions (range: 3–10), the best responses included CR in seven patients (53.8%), nCR in two patients (15.4%), VGPR in two patients (15.4%), and PR in two patients (15.4%). Median time to VGPR was one month. At 10 months, the OS was 90%, and PFS 54.7%. Three patients progressed, one of whom died of ruptured hepatic plasmacytoma. The most frequent toxicity was haematological especially neutropenia (all grades: 92.3%, Grade 3/4: 76.9%), infusion reaction (38.5%, all grade 1/2), neuropathy (38.5%, all grade 1/2), gastrointestinal (all grades: 38.5%, grade 3/4 : 7.7%), and sepsis (all grades: 30.8%; grade 3/4: 23.1%). Neutropenia was effectively prevented with prophylactic G‐CSF. Summary/Conclusion: In conclusion, a 3‐weekly dara‐IMiD‐dex regimen is highly efficacious, inducing deep and rapid responses, hence cost‐effective for less affluent countries. In view of prevalent grade3/4 neutropenia despite less frequent dara, 3‐weekly dara might be more suitable for Asian patients. image
AB0568 THE EFFECT OF DEPRESSIVE AND ANXIETY ON QUALITY OF LIFE IN PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUSIN RENAISSANCE COHORT
Authors: Lyubov Vorobyova, Elena Aseeva, Sergey Solovyev
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) patients are at high risk of depression and anxiety. These two states cause severe loss of health related quality of life (HRQoL) for patient with SLE. <h3>Objectives:</h3> The aim of the current study was to assess the effect of depressive and anxiety on HRQoL in a cohort of patients with systemic lupus erythematosus in Russian Federation (RENAISSANCE). <h3>Methods:</h3> Consecutive patients who fulfilled SLICC 2012 criteria for SLE were recruited. Depressive and anxiety symptoms were assessed by the Hospital Anxiety and Depression (HAD) scale (0-21 points). Health-related quality of life (HRQoL) was assessed by the validated specific questionnaires LupusQoL-Russian. Disease activity was evaluated by the SLEDAI-2K, and chronic damage by the Systemic Lupus International Collaborating Clinics Damage Index score (SDI). <h3>Results:</h3> 328 Russian SLE patients were enrolled in the study (M/F 30/298, mean age 34.4±11.5 years, mean disease duration 106.3±97.9 months; mean SLEDAI 2K 9.6±8.0; mean SDI 0.2±0.6. 34 (10,3%) patients had HADS-depression score of ≥10 and 76 (23,1%) of patients had HADS-anxiety score of ≥10. Patients with depressive score of ≥10 had significantly lower the scales "Planning", "Emotion health" and "Fatigue" (p&lt;0,0001) of the LupusQoL than those with score &lt;10. Similarly, significant lower "Emotion health" and "Fatigue" (p&lt;0,0001) were noted in those patients with HAD-anxiety score ≥10 compared to those &lt;10 and they also had low score of "Burden to others" unlike those who are not anxiety. (Table 1). <h3>Conclusion:</h3> Depressive and anxiety symptoms in SLE patients and were associated with significantly poorer HRQoL. <h3>Disclosure of Interests:</h3> None declared
Abstract 16453: Drug-Eluting Stent Event Registry of Thrombosis (DESERT): The International Drug-Eluting Stent Thrombosis Registry
Authors: Ron Waksman, Rebecca Torguson, Kimberly Kaneshige, Ajay Kirtane, Thomas Ryan, Lorenz Raber, Robert Applegate, Sergio Waxman, David Cohen, Paul Gordon
Journal: Circulation (2012)

Background: Stent thrombosis (ST) frequently presents as an acute event triggering myocardial infarction (MI) or death. Given the low ST event rates, single-center studies are limited when evaluati...
Abstract 18116: Patients With Heart Failure Eat Same Quality of Diet as Their Family Caregivers
Authors: Misook L Chung, Debra K Moser, Junghee Kang, Terry A Lennie
Journal: Circulation (2017)

Introduction: Poor nutrition increases hospitalization risk in patients with heart failure (HF). Patients with HF may eat a different, more restrictive, diet than family members placing them at hig...
Distinct solubility and cytotoxicity regimes of paclitaxel-loaded cationic liposomes at low and high drug content revealed by kinetic phase behavior and cancer cell viability studies
Authors: Victoria M. Steffes, Meena M. Murali, Yoonsang Park, Bretton J. Fletcher, Kai K. Ewert, Cyrus R. Safinya
Journal: Biomaterials (2017)
AB1229 RHEUMATIC DISEASES REMISSION DURING PREGNANCY: MYTH OR REALITY? FACT OR HOPE?
Authors: Euthalia Roussou, Josie O’heney, Victoria Sampson, Asma Aziz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> A Rheumatology Obstetric Combined Clinic (ROCC) has been running in our trust since 2013 for patients with any musculoskeletal (Msk) rheumatological disease. Observing pregnant ladies in this clinic it became noticeable that patients with msk diseases do not always go into remission during pregnancy. <h3>Objectives</h3> To register their perception of disease activity during pregnancy and from their memory of that disease activity before pregnancy. A secondary aim was to assess whether the remission (or flare) during pregnancy was disease specific or trimester specific. <h3>Methods</h3> Patients with Msk disorders attending ROCC were given 2 different 10 cm visual analogue scales (VAS) asking them to grade the current (at the time of the assessment in ROCC) disease activity and their perceived disease activity prior to pregnancy. The recorded diseases were: (1) Lupus and other Connective Tissue Diseases= 18 [(33.3%) of whom 13 were having Lupus and 5 Sjogren's syndrome, (2)SPAs =16 [(28.6%) of whom 4 had Ankylosing Spondylitis (AS) and 12 Psoriatic arthritis (PsA)], (3) Rheumatoid Arthritis (RA) =9 (16.7), Antiphospholipid Syndrome (APS) =7 (13%) and other =4 (7.4%). In the "other" group there was 1 patients with sarcoidosis, 1 with Adult Onset Still's disease, 1 JIA which progressed to CREST, 1 knee pain. The last group was excluded from the analysis. SPSS was used for statistical analysis and chi square to assess the difference between the 2 groups <h3>Results</h3> We analyzed data from 50 patients who attended the ROCC. At the time of presentation mean age ( ±sd) was 33.4 years (± 4.29) range 22-43y while age of disease presentation was 25.5 ( ±8.06). The weeks (w) of pregnancy during the time of assessment were (mean) 22.2 (±8.6) range 8-37 w. ESR (mean in mmHg) was 27 (± 21.7), CRP 13.6 ( ±14.18). Disease activity at presentation on a VAS was 4.24 (± 2.8) while reported disease activity prior to pregnancy was exactly the same of 4.24 ( ± 3.07). Looking at groups of diseases RA and SpA patients showed reduction in the reported disease activity during pregnancy while CTDs and APS showed an increase, both of which however was not statistically significant (ss (table1) Looking at DA according to trimester, it was in the 1st trimester (up to week 13) that patients were reported remision. (table 2 and figure 1). <h3>Conclusion</h3> In our group of pregnant patients with Msk diseases the overall disease activity is the same during pregnancy and before as measured by a VAS. Looking at the diseases patients with RA and SpA showed some reduction and patients with CTDs and APS showed an increase both not statistically significant. Looking at reported VAS according to trimester of pregnancy, it is in the 1st trimester that pregnant patients report reduced activity. <h3>Acknowledgement</h3> Thanks to pregnant women filling the questionnaire <h3>Disclosure of Interests</h3> None declared
Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction
Authors: Akitoshi Hara, Hiroki Kobayashi, Naoya Asai, Shigeyoshi Saito, Takahiro Higuchi, Katsuhiro Kato, Takahiro Okumura, Yasuko K. Bando, Mikito Takefuji, Yasuyuki Mizutani, Yuki Miyai, Shoji Saito, Shoichi Maruyama, Keiko Maeda, Noriyuki Ouchi, Arata Nagasaka, Takaki Miyata, Shinji Mii, Noriyuki Kioka, Daniel L. Worthley, Toyoaki Murohara, Masahide Takahashi, Atsushi Enomoto
Journal: Circulation Research (2019)

Myofibroblasts have roles in tissue repair following damage associated with ischemia, aging, and inflammation and also promote fibrosis and tissue stiffening, causing organ dysfunction. One source of myofibroblasts is mesenchymal stromal/stem cells that exist as resident fibroblasts in multiple tissues. We previously identified meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue), a glycosylphosphatidylinositol-anchored membrane protein, as a specific marker of mesenchymal stromal/stem cells and a regulator of their undifferentiated state. The roles of meflin in the development of heart disease, however, have not been investigated.We examined the expression of meflin in the heart and its involvement in cardiac repair after ischemia, fibrosis, and the development of heart failure.We found that meflin has an inhibitory role in myofibroblast differentiation of cultured mesenchymal stromal/stem cells. Meflin expression was downregulated by stimulation with TGF (transforming growth factor)-β, substrate stiffness, hypoxia, and aging. Histological analysis revealed that meflin-positive fibroblastic cells and their lineage cells proliferated in the hearts after acute myocardial infarction and pressure-overload heart failure mouse models. Analysis of meflin knockout mice revealed that meflin is essential for the increase in the number of cells that highly express type I collagen in the heart walls after myocardial infarction induction. When subjected to pressure overload by transverse aortic constriction, meflin knockout mice developed marked cardiac interstitial fibrosis with defective compensation mechanisms. Analysis with atomic force microscopy and hemodynamic catheterization revealed that meflin knockout mice developed stiff failing hearts with diastolic dysfunction. Mechanistically, we found that meflin interacts with bone morphogenetic protein 7, an antifibrotic cytokine that counteracts the action of TGF-β and augments its intracellular signaling.These data suggested that meflin is involved in cardiac tissue repair after injury and has an inhibitory role in myofibroblast differentiation of cardiac fibroblastic cells and the development of cardiac fibrosis.
PF654 EPIGENETIC ALTERATION OF CSK BINDING PROTEIN(CBP) IN MYELOPROLIFERATIVE NEOPLASMS COMPLEMENTS THE JAK2V617F MUTATION
Authors: J. Huang, X. Ye
Journal: HemaSphere (2019)

Background: Csk binding protein (CBP), a ubiquitously expressed transmembrane protein, functions as a suppressor of Src‐mediated tumor progression by promoting the inactivation of Src. CBP is widely reported to act as a scaffold in the Csk‐mediated negative regulationof Src family kinases (SFKs). First, CBP is phosphorylated by SFKs, then it associates withC‐terminal Src kinase (Csk) through a specific site (Tyr‐317 in humans) and brings it into proximity with membrane‐associated SFKs. After that, Csk phosphorylates the C‐terminal negative regulatory tyrosine residue of SFKs, which suppresses their activation. SFKs are membrane‐associated non‐receptor protein tyrosine kinases that play pivotal roles in regulating various cellular processes including proliferation, differentiation, adhesion, migration, and survival. Thus, CBP plays the opposite role in various Csk‐mediated cellular processes and might be a significant target for Csk‐mediated tumors. Aims: To explore the role of CBP in myeloproliferative neoplasms complements the JAK2V617F mutation. Methods: Bone marrow of 78 JAK2/V617F mutation positive MPN patients were collected, including 18 of 78 idiopathic myelofibrosis, 32 of 78 polycythaemia vera and 28 of 78 essential thrombocythaemia. The mononucleated cells separated, RNA extracted and the CBP expression level detected using real‐time quantitative PCR and MSP. SPSS 23.0 used for data analysis. Results: We identified CBP as a functional tumor suppressor gene frequently methylated in myeloproliferative neoplasms complements the JAK2V617F mutation. We further uncovered CBP as one of the up regulated genes in JAK2/V617F mutation positive cell lines after pharmacologic demethylation with 5 aza 2’ deoxycytidine (Aza). Methylation of CBP was detected in several JAK2/V617F mutation positive cells. Aberrant methylation was further detected in 60% of various types of JAK2/V617F mutation positive MPN, but not in any normal PBMC sample, and is thus tumor specific. The levels of CBP mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting CBP may be epigenetically inactivated in MPN patients. Aza treatment led to CBP promoter demethylation and transcriptional reactivation in silenced cell lines, indicating a methylation mediated silencing. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Summary/Conclusion: Our results indicate that epigenetic inactivation of CBP contributes to the constitutiveactivation of JAK2/STAT signaling. CBP methylation is a frequent event in myeloproliferative neoplasms complements the JAK2V617F mutation. Restoration of CBP expression by HMA may contribute to clinical treatment for MPN patients.