tbuckley/cabot-search huggingface dataset:
AB0305 ALLERGIC SYMPHTOMS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Olga Brzezińska, Anna Lewandowska-Polak, Marek Kowalski, Joanna Makowska
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> One of the hypothesis of RA pathogenesis is that autoimmune process in rheumatoid arthritis starts within the airways. The factors leading to increased antiCCP antibodies formation within the airways are not fully understood. People with allergies to inhaled allergens suffer from chronic inflammation within upper and lower airways. <h3>Objectives</h3> The aim of this study was study was to assess the prevalence of symptoms of upper and lower airways allergic diseases in patients with rheumatoid arthritis as compared to general population prevalence. <h3>Methods</h3> The study group consisted of 96 patients with RA (age years – 46,69±15,70 women-93%, men – 7%). Control group consist 1685 subjects from Lodz population (47,89±15,11 women-55%, men-45%). All responders completed a screening test for allergy symptoms, 60 of RA and all controls were asked to complete a detailed survey consisting of 30 questionnaires based on GA<sup>2</sup>LEN Global Allergy and Asthma Network protocol include diagnoses and separate symptoms of allergic diseases. <h3>Results</h3> In screening questionnaire 16,84% of RA patients and 7,24% control declare that suffer from asthma (p&lt;0,001). The incidence of wheezing in both groups was statistically insignificant (30,00% RA vs 20,65% control; p&gt;0,05), however the coexistence of dyspnoea and wheezing was more frequent in the group of patients with RA (44,83% vs 14,01%; p&lt;0,001) as well as wheezing without symptoms of infection (55,56% vs 15,37% p&lt;0,001). The frequency of waking up at night due to dyspnea or coughing did not differ significantly between the study and control group (respectively 18,67% vs 12,82 and 33,33% vs 33,35%). The symptoms of upper airway chronic inflammation were also more prevalent in patients with RA as compared to controls. Chronic sinusitis was declared by 26,67% of patients and 10,62% controls (p&lt;0,001), as well as the symptom of post-nasal drip was significantly twice more frequent than in the study group (20,00% vs 9,08%; p&lt;0,005). Symptoms of a nasal allergy are insignificantly more often in RA group (38,33 vs 33,06%). <h3>Conclusion</h3> Increased prevalence of symptoms of upper and lower allergic diseases in patients with RA requires further investigation as chronic inflammation within airways can lead to posttranslational modification of proteins and autoantigen formation. <h3>Disclosure of Interests</h3> None declared
PB1861 ELTROMBOPAG RESOLVED ANEMIA AND THROMBOCYTOPENIA IN A PATIENT WITH FANCONI ANEMIA
Authors: I. Yaman Bajin, Y.M. Akçabelen, C.B. Aker, O. Arman Bilir, D. Gurlek Gokcebay, N. Yarali
Journal: HemaSphere (2019)

Background: Fanconi anemia (FA) is a genetic, progressive bone marrow failure (BMF) syndrome caused by mutations in DNA repair pathway leading to increased apoptosis of hematopoietic cells and resulting in pancytopenia. Pancytopenia requiring transfusions is usually well established by the end of first decade of life. Hematopoietic stem cell transplant (HSCT) is still the only curative treatment option for BMF. Eltrombopag, a thrombopoietin receptor agonist, has been shown to induce hematopoiesis in severe aplastic anemia and decrease transfusion requirement. There has been only a few case reports in the literature of eltrombopag use in FA. Aims: Here we report a patient with FA, where eltrombopag eliminated transfusion requirement. Methods: A 5-year-old Syrian refugee boy was admitted to our hospital with pancytopenia. From his history we learned that he was diagnosed with FA in his country. His physical examination revealed short stature, microcephaly and clinodactyly with hypopigmented skin lesions. His family history revealed first degree consanguinity marrige between parents and his 2 siblings died because of renal failure. Bone marrow was hypocellular and DEB test was compatible with FA. He required once to twice weekly platelets and packed red cell transfusions. Oxymetholone (initially 2.5 mg/kg daily, subsequently increased to 5 mg/kg daily) was started but his transfusion requirement did not changed. He was hospitalized because of neutropenic fever and during his hospital stay platelet levels remained under 10x103/μl and he had platelet refractoriness. Haploidentical HSCT was planned but he started to bleed from gastrointestinal tract and eltrombopag (50 mg/ daily)(3 mg/kg daily) added to the oxymetholone treatment. Results: His platelet and hemoglobin levels started to increase after 1 month and continued to increase gradually. He is transfusion independent for 4 months now. Summary/Conclusion: Progressive bone marrow failure leading to pancytopenia and transfusion requirement is a major problem until HSCT for FA patients. Eltrombopag, has been approved by Food and Drug Administration for chronic immune thrombocytopenia and severe aplastic anemia. Gupta et al. reported a patient with FA that eltrombopag eliminated transfusion requirement. Our case supported the data that eltrombopag can be efficient to increase hemoglobin and platelet levels and eliminate transfusion requirement in patients with FA.
Understanding the factors that shape patterns of nucleotide diversity in the house mouse genome
Authors: Tom R Booker, Peter D Keightley
Journal: Molecular Biology and Evolution (2018)

A major goal of population genetics has been to determine the extent by which selection at linked sites influences patterns of neutral nucleotide diversity in the genome. Multiple lines of evidence suggest that diversity is influenced by both positive and negative selection. For example, in many species there are troughs in diversity surrounding functional genomic elements, consistent with the action of either background selection (BGS) or selective sweeps. In this study, we investigated the causes of the diversity troughs that are observed in the wild house mouse genome. Using the unfolded site frequency spectrum, we estimated the strength and frequencies of deleterious and advantageous mutations occurring in different functional elements in the genome. We then used these estimates to parameterize forward-in-time simulations of chromosomes, using realistic distributions of functional elements and recombination rate variation in order to determine whether selection at linked sites can explain the observed patterns of nucleotide diversity. The simulations suggest that BGS alone cannot explain the dips in diversity around either exons or conserved noncoding elements. A combination of BGS and selective sweeps produces deeper dips in diversity than BGS alone, but the inferred parameters of selection cannot fully explain the patterns observed in the genome. Our results provide evidence of sweeps shaping patterns of nucleotide diversity across the mouse genome and also suggest that infrequent, strongly advantageous mutations play an important role in this. The limitations of using the unfolded site frequency spectrum for inferring the frequency and effects of advantageous mutations are discussed.
THU0144 ECHOCARDIOGRAPHIC ABNORMALITIES AMONG HISPANIC PATIENTS WITH RHEUMATOID ARTHRITIS: A CASE CONTROL STUDY
Authors: José Ramón Azpiri-López, Dionicio Ángel Galarza-Delgado, Iris Jazmin Colunga-Pedraza, Carolina Marlene Martínez-Flores, Karla Paola Cuéllar-Calderón, Ileana Cecilia Reynosa-Silva, Marielva Castro-González, Raymundo Pineda, Guillermo Contreras
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease that mainly affects the synovial joints. Subjects with RA have an increased cardiovascular (CV) morbimortality (1). This increase in cardiovascular diseases (CVD) is not explained by traditional risk factors (2). Screening for CVD in RA patients is an essential part of CV risk management. Echocardiography is a simple, non-invasive approach that provides reliable markers for cardiac evaluation (3). <h3>Objectives</h3> To determine the prevalence of echocardiographic abnormalities in RA patients and compare them to matched controls. <h3>Methods</h3> Observational, cross-sectional study. RA patients aged 40 to 75 years that fulfilled the 2010 ACR/EULAR classification criteria and matched controls were included. Patients with a poor ultrasound window, history of previous atherosclerotic CVD (ischemic heart disease, cerebrovascular accident or peripheral arterial disease) and pregnancy were excluded. Transthoracic echocardiogram was performed and reviewed by 2 board-certified cardiologists. Differences were solved by consensus. Descriptive analysis was done with frequencies (%) and median (q25-q75), and comparisons with Chi-square and Mann U-Whitney's test. <h3>Results</h3> A total of 133 subjects were included. Baseline characteristics are shown in Table 1. Groups were well balanced, with no differences among them. Echocardiographic comparisons are shown in Table 2. Prevalence of abnormal left ventricle (LV) geometry was higher in RA patients (<i>p</i><i>=</i> .038), as were mitral and tricuspid valvular dysfunction (p&lt;0.001). The LV ejection fraction was lower in RA subjects (<i>p</i><i>=</i> .044). LV= Left ventricle. <h3>Conclusion</h3> Patients with rheumatoid arthritis have higher prevalence of mitral and tricuspid valves dysfunction in our population, and greater left ventricular geometry alterations, compared to controls. As the left ventricular ejection fraction is a strong prognosticator for CV disease, echocardiography might be a simple non-invasive tool for cardiac risk screening in RA. <h3>References</h3> [1] Avina-Zubieta JA, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum2008; 59(12):1690-1697. [2] Curtis JR, et al. Is Rheumatoid Arthritis a Cardiovascular Risk-Equivalent to Diabetes Mellitus?Arthritis Care Res. 2018Nov; 70(11):1694-1699. [3] Fine NM, et al. Evaluation of myocardial function in patients with rheumatoid arthritis using strain imaging by speckle-tracking echocardiography. Ann Rheum Dis. 2014; 73(10):1833-1839. <h3>Disclosure of Interests</h3> None declared
PB2320 PHASE II STUDY OF IMATINIB MESYLATE PLUS MYCOPHENOLATE MOFETIL FOR PEDIATRIC STEROID‐REFRACTORY SCLEROTIC/FIBROTIC TYPE CHRONIC GRAFT‐VERSUS‐HOST DISEASE
Authors: H. J. Kang, J. Y. Choi, H. Kim, H. J. Baek, H. Kook, J. M. Lee, H. Y. An, K. T. Hong, H. Y. Shin
Journal: HemaSphere (2019)

Background: Chronic graft‐versus‐host disease (cGVHD) is the most common late complication following allogeneic stem cell transplantation. Sclerotic/fibrotic cGVHD is one of the severe type, and often refractory to standard and secondary therapy. Aims: In this study, we evaluated the efficacy and safety of imatinib mesylate and mycophenolate mofetil (MMF). Methods: In non‐randomized, open‐label, single‐arm, multi‐center, prospective phase II study, we enrolled patients with steroid‐refractory sclerotic/fibrotic type cGVHD. Participants were treated with MMF at a dose of 15‐20 mg/kg (maximum 1 g) bid and imatinib mesylate at the initial dose of 260 mg/m 2 /day (maximum 400 mg) in combination with previous cGVHD treatment. The primary endpoints was overall (complete and partial) response rate at 1 year. Secondary endpoints included safety, quality of life, discontinuation of steroid and overall survival (OS) rate. Results: A total of 13 patients were enrolled between October 2013 and July 2017. The median age was 10.4 years (range 5.0‐20.1 years). Five of the 13 patients had previously experienced acute GVHD. The diagnoses were acute lymphoblastic leukemia in 5, acute myeloid leukemia in 3, chronic granulomatous disease in 3, neuroblastoma in 1 and hemophagocytic lymphohistiocytosis in 1 patient. Nine of the 13 patients achieved partial response (PR), 2 showed stable diseases (SD), and 1 died of pulmonary infection and progression of chronic lung GVHD. The remaining 1 patient died of primary disease progression. The overall response rate was 69.2 %. Nine of the 13 patients were able to reduce or discontinue steroids. Among 13 patients, 6 patients showed improvements in Lee cGVHD symptom scale score to assess quality of life. Common adverse events included grade 1‐2 liver enzyme, creatinine elevations and fever. The 2‐ and 5‐year OS rate was 76.9% and 67.3%, respectively. Summary/Conclusion: Although limited by a small sample size, Gleevec plus MMF for cGVHD showed promising results with acceptable toxicity.
MUTATIONAL LANDSCAPE OF PRIMARY MEDIASTINAL B-CELL LYMPHOMA (PMBCL) BY MEANS OF CIRCULATING TUMOR DNA ANALYSIS
Authors: A. Rivas-Delgado, F. Nadeu, A. Enjuanes, L. Magnano, P. Mozas, M. Osuna, S. Martín, T. Baumann, Catrejon N. de Anta, O. Balague, J. Delgado, N. Villamor, E. Campo, E. Gine, A. Lopez-Guillermo
Journal: HemaSphere (2019)
PS1094 MANAGING CYTOKINE RELEASE SYNDROME (CRS) AND NEUROTOXICITY WITH STEP‐FRACTIONATED DOSING OF MOSUNETUZUMAB IN RELAPSED/REFRACTORY (R/R) B‐CELL NON‐HODGKIN LYMPHOMA (NHL)
Authors: S.‐S. Yoon, M. Matasar, L.H. Sehn, S. Assouline, N.L. Bartlett, F. Bosch, C.M. Diefenbach, I. Flinn, J.Y. Hong, W.S. Kim, L. Nastoupil, S.J. Schuster, M. Shadman, B. Bender, W. Chu, G. Hernandez, A. Kwan, B. McCall, I. Sison, C. Wang, M.C. Wei, S. Yin, K. Yousefi, E.L. Budde
Journal: HemaSphere (2019)

Background: T‐cell directed therapies (e.g. CAR‐T, blinatumomab) are associated with significant risk of Grade (Gr) ≥3 neurotoxicity and CRS/infusion‐related reaction (IRR). Mosunetuzumab is a CD20/CD3 bispecific antibody that directs T‐cells to engage and eliminate malignant B‐cells. Aims: To report safety results from an ongoing Phase 1/1b study (NCT02500407) of mosunetuzumab in patients (pts) with R/R B‐cell NHL. Methods: Pts received ascending doses on Day 1, Day 8, and Day 15 of Cycle 1 (step‐fractionation), then a fixed dose on Day 1 of every 21‐day cycle thereafter, up to a maximum of 17 cycles. Primary outcome measures included safety and efficacy. Results: As of October 23, 2018, 114 pts who received step‐fractionated dosing of mosunetuzumab were evaluable for safety ( Table ). The majority of adverse events (AE) occurred during Cycle 1 and 2. Neurologic AEs (NAE), defined from Nervous System or Psychiatric System Organ Classes, were mostly low grade, transient (median duration 4 days) and reversible; most common were headache (14%) and dizziness (8%). Gr ≥3 NAEs occurred in 4 pts (4%), with only 1 treatment‐related event (hepatic encephalopathy). CRS/IRR was reported in 25% of pts, with only 1 Gr 3 event. Most common CRS symptoms were pyrexia (86%), chills (38%), tachycardia and headache (14% each). There were no Gr 5 events related to CRS or NAEs. No apparent dose toxicity relationship was observed with step‐fractionation in these pts, despite escalation of the Cycle 1 Day 15 dose to 20 mg, consistent with observed peak IL‐6 levels after a low Cycle 1 Day 1 dose. In these pts, objective responses were observed in 24/73 (33%; complete response [CR], 13 [18%]) aggressive NHL and 17/32 (53%; CR, 10 [31%]) indolent NHL pts. Summary/Conclusion: Step‐fractionation has enabled continued dose escalation of mosunetuzumab with no apparent increases in toxicity, exhibiting a promising risk‐benefit profile. image
AB1288 PREVENTION OF VENOUS THROMBOEMBOLISM AND THE RISK OF POSTOPERATIVE COMPLICATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS AFTER TOTAL HIP ARTHROPLASTY:
Authors: Alexey Rybnikov, Evgenij Bialik, Tatiana Reshetnyak, Sergey Makarov, Alexander Khramov, Sergey Maglevaniy
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> According to the administrative data, confirmed by several meta-analyses, patients with rheumatoid arthritis (RA) in comparison with the General population shows an increased risk of venous thromboembolic complications more than twice. Drug prevention can reduce the risk of venous thromboembolism (VTE) in patients with rheumatic diseases. <h3>Objectives:</h3> The aim of this study was to analyze frequency of VTE, risk of bleeding and complications of the postoperative wound in patients with RA and osteoarthritis (OA) after total hip arthroplasty (THA). <h3>Methods:</h3> <b>S</b>tudy included 486 patients (212 - with RA and 274 - with OA) who underwent primary THA. Each group of patients was divided into 3 subgroups by type of drug therapy (1-nadroparin calcium; 2-dabigatran etexilate; 3-nadroparin calcium with transfer to dabigatran etexilate). Intra-and postoperative blood loss and the wound healing process were assessed during the first 7 days after surgery. <h3>Results:</h3> Postoperative VTE were reported in 36 (7.4%) of 486 patients. VTE in patients with RA were detected significantly less frequently than in OA (1.2% and 6.1%, p = 0.0013). Bleeding that required transfusion of blood in RA were found significantly more often than in OA (respectively 14.4% and 5.7% of cases; P&lt;0.001). The number of cases requiring cancellation of anticoagulant therapy in patients with RA was significantly higher compared with the OA group (6.6% and 1.4%, respectively). Slow wound healing in RA was more common (n = 56; 26.4%) than in OA (n = 14; 5.1%). In patients who underwent monotherapy with calcium nadroparin VTE occurred more often than when using combination therapy (p&lt;0.0001) and more often than in the group of dabigatran etexilate (p=0.054). <h3>Conclusion:</h3> The frequency of VTE, the risk of bleeding and complications of postoperative wound in patients with RA and OA after THA were analyzed. So, our study determined the dependence of VTE complications and bleeding risk according to the patient's underlying nosology. Also the advantage of combined postoperative therapy over others was evaluated. <h3> Disclosure of Interests:</h3> None declared
Identification of Celastramycin as a Novel Therapeutic Agent for Pulmonary Arterial Hypertension
Authors: Ryo Kurosawa, Kimio Satoh, Nobuhiro Kikuchi, Haruhisa Kikuchi, Daisuke Saigusa, Md. Elias Al-Mamun, Mohammad A.H. Siddique, Junichi Omura, Taijyu Satoh, Shinichiro Sunamura, Masamichi Nogi, Kazuhiko Numano, Satoshi Miyata, Akira Uruno, Kuniyuki Kano, Yotaro Matsumoto, Takayuki Doi, Junken Aoki, Yoshiteru Oshima, Masayuki Yamamoto, Hiroaki Shimokawa
Journal: Circulation Research (2019)

Rationale: Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) accompanying increased production of inflammatory factors and adaptation of the mitochondrial metabolism to a hyperproliferative state. However, all the drugs in clinical use target pulmonary vascular dilatation, which may not be effective for patients with advanced PAH. Objective: We aimed to discover a novel drug for PAH that inhibits PASMC proliferation. Methods and Results: We screened 5562 compounds from original library using high-throughput screening system to discover compounds which inhibit proliferation of PASMCs from patients with PAH (PAH-PASMCs). We found that celastramycin, a benzoyl pyrrole–type compound originally found in a bacteria extract, inhibited the proliferation of PAH-PASMCs in a dose-dependent manner with relatively small effects on PASMCs from healthy donors. Then, we made 25 analogs of celastramycin and selected the lead compound, which significantly inhibited cell proliferation of PAH-PASMCs and reduced cytosolic reactive oxygen species levels. Mechanistic analysis demonstrated that celastramycin reduced the protein levels of HIF-1α (hypoxia-inducible factor 1α), which impairs aerobic metabolism, and κB (nuclear factor-κB), which induces proinflammatory signals, in PAH-PASMCs, leading to reduced secretion of inflammatory cytokine. Importantly, celastramycin treatment reduced reactive oxygen species levels in PAH-PASMCs with increased protein levels of Nrf2 (nuclear factor erythroid 2-related factor 2), a master regulator of cellular response against oxidative stress. Furthermore, celastramycin treatment improved mitochondrial energy metabolism with recovered mitochondrial network formation in PAH-PASMCs. Moreover, these celastramycin-mediated effects were regulated by ZFC3H1 (zinc finger C3H1 domain-containing protein), a binding partner of celastramycin. Finally, celastramycin treatment ameliorated pulmonary hypertension in 3 experimental animal models, accompanied by reduced inflammatory changes in the lungs. Conclusions: These results indicate that celastramycin ameliorates pulmonary hypertension, reducing excessive proliferation of PAH-PASMCs with less inflammation and reactive oxygen species levels, and recovered mitochondrial energy metabolism. Thus, celastramycin is a novel drug for PAH that targets antiproliferative effects on PAH-PASMCs.
Abstract 11806: Utilization of Thrombolytics in Ischemic Stroke in Patients With Cancer
Authors: Jocelyn A Owusu-Yaw, Avirup Guha, Benjamin Buck, P Elliott Miller, Sumeet Pawar, Tariq Ahmad, Farrukh T Awan, Nihar R Desai, Daniel Addison
Journal: Circulation (2018)

Background: Thrombolytic (tPA) therapy significantly improves outcomes among patients with ischemic stroke. We sought to determine the utilization and outcomes of tPA in ischemic stroke patients wi...
SAT0341 THE PREVALENCE OF RENAL FAILUREIN A PROSPECTIVE AXIAL SPONDYLOARTHRITIS COHORT AND POSSIBLE ASSOCIATED FACTORS
Authors: Xabier Michelena-Vegas, Carla Marco Pascual, Xavier González Giménez, Maribel Mora, J Lluch Pons, Jesús Rodríguez, Joan Miquel Nolla, Xavier Juanola-Roura
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Extra-articular manifestations and comorbidities are significant complications in the evolution of patients with spondyloarthritis (SpA). The presence of renal failure (RF) is a multifactorial comorbidity that has been shown to be associated with this disease, and its prevalence has been reported around 5% (COMOSPA<sup>1</sup>). There are no prevalence studies in our environment. <h3>Objectives:</h3> To determine the prevalence and possible factors associated with RF in patients with axial spondyloarthritis (axSpA). <h3>Methods:</h3> Data was retrieved from a prospective database designed for the monitoring of patients with SpA from a large teaching hospital. We only included patients with axSpA. Demographic and clinical data were recorded, as well as possible risk factors associated with RF: arterial hypertension (AHT), smoking status, Diabetes (DM), Dyslipidemia (DL), NSAIDs use and renal function from last test available (we considered RF when eGFR&lt;60 mL/min). Continuous data were compared with Student t-test if the variables presented normal distribution (previous Shapiro-Wilk test) or Mann Whitney U test otherwise. Chi-square or Fisher test was performed if the variable was categorical. <h3>Results:</h3> 339 patients were included. 73.2% were male with a mean age of 56.68 (±14.8) years and a mean age of onset of 32.0 (±11.4) years. The mean disease duration was 32.8 (±11.4) years. 83.7% were HLAB27+. The clinical variables for the whole cohort were: BASDAI 3.56 (±2.13), BASFI 3.74 (±2.65), CRP 5.61 (±6.92) and ESR 2.28 (±0.89). The following risk factors were registered: smokers 58.3%, AHT 33.3%, DL 31.3% and NSAID use of 34.6%. 27.4% of patients were receiving biologic therapy. 41 patients (12.1%) presented RF criteria. Comparison between two groups is shown in table 1. A statistically significant association with RF was found in age, sex, AHT, DL, no use of NSAIDs, higher BASFI and ASDAS indexes as well as ESR value. <h3>Conclusion:</h3> There is a substantial prevalence of RF in patients with axSpA in our cohort. We should maximise our awareness of RF in old patients, those suffering from AHT and DLP, as well as subjects with high BASFI, ASDAS and ESR values. <h3>Reference</h3> [1] Couderc, et al: Renal impairment in SpA; The Journal of Rheumatology2018; 45:6 <h3>Disclosure of Interests:</h3> None declared