tbuckley/cabot-search huggingface dataset:
Aplastic anemia in adult and pediatric hematology
Authors: Charlotte Niemeyer
Journal: HemaSphere (2019)

Learning goals To recognize the clinical implications of our current understanding of SAA pathophysiology To be able to identify an appropriate treatment strategy—immunosuppressive therapy, stem cell stimulation, HSCT—for individual patients with SAA To understand the significance of somatic mutations detected in bone marrow of patients with SAA and hypoplastic MDS. Introduction Immune-mediated severe aplastic anemia (SAA) typically presents with rapidly decreasing blood counts of all lineages and a profoundly hypocellular bone marrow. Much effort has been invested in characterizing its immune signature targeting hematopoietic stem and progenitor cells. In this education session Neal S. Young M.D. will summarize our current understanding of the SAA immune phenotype and outline principles of standard therapy with immunosuppression and more recently stem cell stimulation. Andrea Bacigalupo M.D. will discuss current indications for allogeneic hematopoietic stem cell transplantation (HSCT) in SAA and develop future perspectives of upfront alternative donor grafts. It has long been appreciated that abnormal clones can expand in SAA bone marrow. Judith Marsh M.D. will review the impact of the immune signature of SAA and hypoplastic myelodysplastic syndrome (MDS) on the development of somatic mutations and outline their clinical significance for classification, therapy, and outcome.
Abstract 13980: Angiopoietin-Like Protein 2 is a Critical Inflammatory Mediator of Atherosclerosis
Authors: Eiji Horio, Koichi Kaikita, Keishi Miyata, Tsuyoshi Kadomatsu, Hirokazu Tazume, Tian Zhe, Kenichi Tsujita, Shinji Tayama, Seiji Hokimoto, Seigo Sugiyama, Motohiro Takeya, Hisao Ogawa, Yuichi Oike
Journal: Circulation (2012)

Chronic vascular inflammation plays crucial roles in pathogenesis of atherosclerosis, however the molecular mechanisms have not been fully clarified. We previously reported that angiopoietin-like p...
THU0607 CORRELATION BETWEEN ULTRASOUND AND STANDARD RADIOGRAPHY AND BETWEEN ULTRASOUND AND CLINICAL DATA IN RHEUMATOID ARTHRITIS
Authors: ACHEK Mohamed Amine EL, Amel Farhat, Chakib Kraeim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Early diagnosis in Rheumatoid Arthritis (RA) is essential in order to quickly introduce a background treatment to prevent joint destruction. In recent years, ultrasound has become an essential part of the initial assessment of polyarthritis because of its superior sensitivity to clinical examination and standard imaging for the investigation of synovitis, tenosynovitis and erosions. <h3>Objectives:</h3> To evaluate concordance between clinical examination, standard radiography and joint ultrasonography in a heterogeneous group of patients with RA. <h3>Methods:</h3> 40 patients were included in a prospective, transverse and monocentric study conducted in the radiology department of Farhat Hached University Hospital in Sousse over a period of 03 months whatever the level of activity of the disease, the duration of evolution or the treatment received. For each patient, 24 joints were evaluated for a total of 960 joints. Synovitis was scored using clinical examination, B-mode ultrasound, and pulsed Doppler. Concordance between joint swelling assessed by clinical examination, synovial thickening assessed by E-B and inflammation assessed by PD was evaluated by calculating the Kappa coefficient (k). A comparison between the reliability of ultrasound versus standard imaging was evaluated for the detection of bone erosions. The onset of RA, stage, and ultrasound score were assessed by Spearman coefficient. <h3>Results:</h3> 960 joints were studied. The mean age was 54.6 years. The sex ratio was 0.29. The mean duration of illness was 3.4 months. Clinical examination revealed 207 active synovitis versus Ultrasonography: 474 active synovitis. The concordance between clinical examination and ultrasound was very low at the metacarpophalangeal (MCP) (&lt;0.1), low at the proximal interphalangeal (PIP) (0.26) and moderate at wrist (0, 56), ultrasound detected more erosions than standard radiography (56% versus 17%), and a statistically significant correlation was observed between the onset of RA, its stage, and the ultrasound score. <h3>Conclusion:</h3> Evaluation of a heterogeneous group demonstrated that ultrasound completes clinical examination information, particularly at the PIP and MCP levels, and detects erosions earlier than standard imaging. <h3>Disclosure of Interests:</h3> None declared
PS1550 ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION CAN OVERCOME THE POOR OUTCOME OF ADULT PH(+) ACUTE LYMPHOBLASTIC LEUKEMIA -- ON BEHALF OF TAIWAN SOCIETY OF BLOOD AND MARROW TRANSPLANTATION
Authors: T.-D. Tan, J.-L. Tang, M. Yao, J.-P. Gau, P.-N. Wang, S.-P. Yeh, T.-Y. Chen, C.-L. Teng, Y.-C. Liu
Journal: HemaSphere (2019)

Background: Acute lymphoblastic leukemia included Ph(+), Ph-like, and others, and we know that the outcome of Ph(+) ALL was worse as compared with Ph(-). After the introduction of targeted tyrosine kinase inhibitor and allogeneic hematopoietic stem cell transplantation the overall survival improved in historical comparison. Aims: We want to know in real world practice whether the outcome of Ph(+) ALL could be not inferior as compared with Ph(-) after combined TKI and chemotherapy induction therapy followed by allogeneic stem cell transplant. Methods: This is a retrospective study from the data base of Taiwan Society of Blood and Marrow Transplantation (TSBMT) Registry and we compared the overall survival between Ph(+) and Ph(-) ALL. Results: Between 2006 and 2018 we had 526 ALL patients underwent allogeneic hematopoietic stem cell transplantation, with median age of 31 (range 0.7 to 69) and male to female were 55% versus 45%. Pre-transplant disease status included 56% in CR1, 26% in CR2/CR3, 6% were induction failure, and 11% were relapsed patients. Ninty-three (18%) were Ph(+), and 433 (82%) were Ph(-). Seven patient received umbilical cord blood stem cells and 502 (95%) received peripheral blood stem cells, 37 (7%) received bone marrow stem cells, including 26 patients received both bone marrow and peripheral blood stem cells. The overall survival of all patients were 44% at 3 years and 40% at 5 years. For Ph(+) versus Ph(-) patients, 3-year OS were 49% versus 42% and 5-year OS were 49% versus 38%, respectively.Summary/Conclusion: After the introduction of combination of targeted TKI plus chemotherap induction therapy followed by allogeneic stem cell transplantation, the outcome of Ph(+) ALL is not inferior to Ph(-) patients.
Abstract 20759: DNA Methylation Signature of Statin Therapy
Authors: Chen Yao, Shih-Jen Hwang, Michael Mendelson, Tianxiao Huan, Chunyu Liu, Daniel Levy
Journal: Circulation (2017)

Introduction: Statins are a family of lipid-lowering drugs that lower circulating LDL-cholesterol (LDL-C) levels. Individual difference in LDL-C response to statin treatment may be attributed to va...
PF728 COMPARISON OF ALLOPURINOL AND FEBUXOSTAT FOR PREVENTION OF HYPERURICEMIA AND TUMOR LYSIS SYNDROME IN ACUTE LEUKEMIAS
Authors: S.P. Mirgh, M. Mahapatra, T. Seth, R. Dhawan, M. Aggarwal, R. Saxena, H. Pati, S. tyagi
Journal: HemaSphere (2019)

Background: Serum uric acid control is of prime importance in prevention of tumor lysis syndrome. Each mg/dl rise in uric acid increases the risk of tumor lysis syndrome and renal events by 1.75‐fold and 2.25‐fold respectively. We compared two xanthine oxidase inhibitors ‐ allopurinol and febuxostat as hypouricemic agents in patients of acute leukemias. Aims: The aims of the study were to assess the change in serum uric acid levels from baseline to day+7 after chemotherapy and to determine the incidence of tumor lysis syndrome in both groups. Methods: In this single‐institution prospective cohort study (study period – January2017 – July2018), acute leukemia patients scheduled to receive induction chemotherapy were administered either allopurinol or febuxostat, starting atleast 1 day prior to chemotherapy till 8 days after chemotherapy. Daily dose for Allopurinol was 300 mg/m2 and for febuxostat, it was 80 mg (10 mg daily for children &lt; = 15years). Patients with baseline uric acid level &gt;8 mg/dl, presence of hepatic or renal dysfunction and history of receiving rasburicase were excluded. The primary objective was to compare both the drugs in terms of decrease in serum uric acid levels analysed by area under curve (AUC) for a 7‐day treatment period. Results: A total of 120 patients (60 patients in each group) were recruited. Both groups were comparable in terms of gender, age, diagnosis and baseline uric acid levels. Mean AUC of serum uric acid day1–8 was 457.68 ± 27.55 mg‐h/dL versus 532.32 ± 34.39 mg‐h/dL, in favour of febuxostat [P = 0.09].The difference between the two study drugs was statistically significant for febuxostat on day+3 [ P &lt; 0.05] (Figure 1).10% (n = 6) patients on allopurinol developed TLS compared to 3.33% (n = 2) patients on febuxostat. The Odds ratio for tumor lysis syndrome in patients receiving febuxostat relative to those receiving allopurinol was 0.33. Drug related adverse events were 38.33% (n = 23) in allopurinol group, in contrast to 11.66% (n = 7) in the febuxostat group. Most common adverse event in allopurinol arm was gastrointestinal, whereas in febuxostat arm, it was asymptomatic transaminitis. Cutaneous reactions (6.6%;n = 4) were noticed only in allopurinol group. Summary/Conclusion: Irrespective of type of leukemia, lactate dehydrogenase levels, leukocyte counts and baseline uric acid levels, febuxostat in comparison to allopurinol, performed non‐inferior with respect to its uric acid lowering efficacy. It had relatively lesser risk of tumor lysis syndrome with a trend towards significance and a better safety profile. image
Abstract 2313: Atrial Fibrillation Augments Single-unit Sympathetic Nerve Activity
Authors: Hisayoshi Murai, Shigeo Takata, Michirou Maruyama, Tatunori Ikeda, Manabu Nakano, Motoaki Hirasawa, Hiroshi Furushou, Masayuki Takamura, Shuiti Kaneko
Journal: Circulation (2006)

Background: Although prognosis of rate-control therapy in atrial fibrillation (AF) has recently been shown to be similar to that of rhythm-control therapy, the sympathetic neural activity in rate-c...
Abstract 106: G Protein-coupled Receptor Kinase 2 Associates With Mitochondrial Proteins and Negatively Alters Mitochondrial Respiration After Myocardial Infarction
Authors: Jessica Pfleger, Priscila Sato, Kunhong Xiao, Walter J. Koch
Journal: Circulation Research (2016)

During cardiac injury or stress, G protein-coupled receptor (GPCR) kinase 2 (GRK2) expression levels and activity are increased, leading to a desensitization of myocardial β-adrenergic receptors (βARs) and contributing to the loss of contractile reserve. Up-regulated GRK2 has been shown to be pathogenic in the post-injured heart and is involved in the promotion of heart failure (HF). Consequently, inhibition of GRK2 has been shown to rescue several animal models of HF, as demonstrated by cardiac expression of the βARKct, a peptide inhibitor of GRK2. There is new evidence that GRK2 has other, non-GPCR dependent pathological functions within cardiomyocytes. For example, during conditions that increase oxidative stress, GRK2 has been shown to localize to the mitochondria, where it is a pro-death kinase. βARKct has also been shown to inhibit the mitochondrial translocation of GRK2 due to inhibition of Hsp90 binding, a chaperone found to bind and localize GRK2 to mitochondria. Our objective is to identify the functions and targets of GRK2 in the mitochondria and its role in the development of HF. We hypothesize that GRK2 has mitochondrial targets that impair mitochondrial function in vivo, contributing to the pathogenesis of HF. Our results show that ADP-stimulated and maximal respiration are significantly decreased in mitochondria isolated from mouse hearts 2 weeks post-myocardial infarction (MI). Cardiac-specific expression of the βARKct rescued the reduction in mitochondrial respiration post-MI, in the presence of pyruvate or palmitoylcarnitine. To identify the mitochondrial targets of GRK2, we performed interactome and phospho-interactome analyses on GRK2 immunoprecipitates from neonatal rat cardiomyocytes subjected to oxidative stress. These results revealed that GRK2 interacts with several mitochondrial proteins, including those involved in metabolism, oxidative stress, calcium handling and cell death. Thus we propose that during ischemia, an increase in mitochondrial GRK2 results in its association with proteins that compromise respiration and contribute to myocardial damage and HF. This demonstrates that understanding both the canonical and non-canonical roles of GRK2 in HF is essential for more targeted intervention for therapy.
THU0285 UMBILICAL ARTERIAL DOPPLER ULTRASONOGRAPHY PREDICTS LATE PREGNANCY OUTCOMES IN PATIENTS WITH LUPUS NEPHRITIS: A MULTICENTER STUDY FROM SOUTHERN CHINA
Authors: zhongping zhan, Dongying Chen, Shiwen Yuan, Xiaodong Wang, Yanfeng Zhan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Compared with the general population, patients with lupus nephritis (LN) are still at high risk of adverse pregnancy outcomes (APOs). Umbilical artery is the last vessel upstream of the placenta and is particularly important for placental perfusion and foetal development. Increased umbilical artery resistance could be traced by Doppler velocimetry, which is frequently related to pre-eclampsia, intrauterine growth restriction (IUGR), and foetal distress. Umbilical artery Doppler is used as a screening tool for placenta-related diseases in the general population. However, the predictive value in complications of LN pregnancies has not been widely assessed. <h3>Objectives</h3> To investigate the fetal adverse pregnancy outcomes (APOs) and the predictive value of umbilical arterial Doppler ultrasonography in the third trimester in pregnant women with LN. <h3>Methods</h3> A retrospective cohort study enrolling 203 LN patients with pregnancies from 2007 to 2017 from three centers was performed. These patients received umbilical arterial Doppler ultrasound examination during 28-34 gestational weeks. Doppler velocity waveforms of the umbilical arteries were assessed with resistance index (RI), systolic/diastolic ratio (S/D) and pulsatility index (PI). <h3>Results</h3> Fetal APOs occurred in over half of the patients (103/203, 50.7%). Sixty-six pregnancies (66/203, 32.5%) ended with preterm births. The incidence rate of IUGR was 18.2% (37/203). Fetal distress was noted in 23 pregnancies (23/203, 11.3%). All the Doppler parameters were higher in patients with IUGR, fetal distress and composite APOs than in patients without any APOs. Patients with IUGR and fetal distress had significantly higher values of PI, RI, and S/D. It was noted that PI, RI and S/D was higher in patients with premature delivery than those with full-term delivery. However, only the difference of RI and S/D reached statistical significance. RI indicated the highest risk of IUGR and composite APOs. The cut-off values were 0.66 and 0.67, respectively. Sensitivities were 51.4% and 33.7%, and specificities were 87.4% and 92.1%. S/D was also a best predictor for IUGR, with the optimal cut-off value of 2.88. Sensitivity and specificity were comparable with RI. PI over 0.84 was an ideal indicator for fetal distress with an optimal combination of sensitivity (89.5%) and specificity (51.6%). <h3>Conclusion</h3> Fetal complications were frequent in patients with LN. Umbilical arterial Doppler ultrasonography was a useful measure to predict late IUGR, fetal distress, and the composite APOs. <h3>Acknowledgement</h3> No <h3>Disclosure of Interests</h3> None declared
Neuronally derived extracellular vesicles: an emerging tool for understanding Alzheimer’s disease
Authors: Luke S. Watson, Eric D. Hamlett, Tyler D. Stone, Catrina Sims-Robinson
Journal: Molecular Neurodegeneration (2019)

In order for Alzheimer's disease (AD) to manifest, cells must communicate "pathogenic material" such as proteins, signaling molecules, or genetic material to ensue disease propagation. Small extracellular vesicles are produced via the endocytic pathways and released by nearly all cell types, including neurons. Due to their intrinsic interrelationship with endocytic processes and autophagy, there has been increased interest in studying the role of these neuronally-derived extracellular vesicles (NDEVs) in the propagation of AD. Pathologic cargo associated with AD have been found in a number of studies, and NDEVs have been shown to induce pathogenesis in vivo and in vitro. Exogenous NDEVs are also shown to reduce plaque burden in AD models. Thus, the NDEV has the potential to become a useful biomarker, a pathologic potentiator, and a therapeutic opportunity. While the field of NDEV research in AD is still in its infancy, we review the current literature supporting these three claims.
Abstract 15739: Overexpression of the Longevity Gene SIRT6 in Myeloid Cells Reduced Left Ventricular Hypertrophy After Mi
Authors: La-Paz Levin-Kotler, Uri Amit, Tammy Ben-Mordechai, dahlia palevski, Nili Naftali-Shani, Daria Lendengolts, Natalie Landa, Haim Cohen, Jonathan Leor
Journal: Circulation (2017)

Background and Aim: The longevity gene SIRT6 provides anti-ageing, anti-inflammatory, and anti-hypertrophic properties that might protect against several cardiovascular diseases. Because macrophage...
AB1336C COMPARISON OF NORMALIZED MUSCLE ACTIVATION EFFECTS OF THREE DIFFERENT EXERCISES ON SUPRAHYOID MUSCLES IN HEALTHY SUBJECTS
Authors: Hasan erkan Kilinc, Yasaroglu Omer Faruk, Arslan Selen Serel, Numan Demİr, Mehmet Akİf Topçuoğlu, Aynur Ayşe Karaduman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The most important airway protection mechanism during swallowing is adequate laryngeal elevation. Suprahyoid muscles are responsible for laryngeal elevation. There are many treatment approaches to improve laryngeal elevation in swallowing rehabilitation. The most common methods are exercises including Shaker exercises, Chin-Tuck Against Resistance (CTAR) exercise, Neuromuscular Electrical Stimulation of suprahyoid muscles and Expiratory Muscle Strength Training (1-4). <h3>Objectives:</h3> The aim of our study was to compare the effects of three different exercises including Shaker, CTAR and a new method Chin Tuck with TheraBand Exercises on suprahyoid muscles activity. <h3>Methods:</h3> Forty-two healthy subjects with a mean age of 27.92±5.02 years (min=18, max=40), of which 50% were male were included. All individuals were divided into three groups; Chin Tuck Against Resistance (CTAR); Group 1, Shaker exercise; Group 2, Chin Tuck Exercise with Theraband; Group 3, with computerized randomization. Surface EMG evaluation was performed to determine electrical activity of the suprahyoid muscles during maximal voluntary isometric contraction (Figure1) and during performing CTAR, Shaker exercise and Chin Tuck with Theraband (Figure 2-4). Normalized suprahyoid muscle activations were calculated as: Recorded Maximum Electrical Activity During Exercise (mV)<b>/</b> Recorded Maximum Electrical Activity During Maximum İsometric Contraction (mV). <h3>Results:</h3> A statistically significant difference was found between three groups in terms of normalized suprahyoid muscle activitty(p&lt;0.001) (Table 1). The difference between three groups was caused by the difference between Group 1 and Group 2 (p&lt;0.001) and between Group1 and Group 3 (p=0.040) in favor of Group 1. No difference was found between Group 2 and Group3 (p=0.104) (Table 2-4). <h3>Conclusion:</h3> In conclusion, primarily CTAR exercise should be included in rehabilitation to increase the suprahyoid muscle activation. In addition, chin tuck exercise with Therband can also be considered as an alternative to CTAR. <h3>References</h3> [1] Shaw GY, et al. Transcutaneous neuromuscular electrical stimulation (VitalStim) curative therapy for severe dysphagia: myth or reality?Annals of Otology, Rhinology &amp; Laryngology.2007;116(1): 36-44. [2] Wheeler-Hegland KM, Rosenbek JC, Sapienza CM. Submental sEMG and hyoid movement during Mendelsohn maneuver, effortful swallow, and expiratory muscle strength training. J Speech Lang Hear Res. 2008;51(5):1072-1087. [3] Yoon WL, Khoo JK, Liow SJ. Chin tuck against resistance (CTAR): new method for enhancing suprahyoid muscle activity using a Shaker-type exercise. Dysphagia. 2014;29(2):243-248. <h3>Disclosure of Interests:</h3> None declared
Abstract 19515: CaMKII Oxidation Causes Increased Atrial Fibrillation in Diabetic Mice
Authors: Olurotimi O Mesubi, Adam G Rokita, Neha Abrol, Yuejin Wu, Biyi Chen, Qinchuan Wang, Jonathan Granger, Elizabeth D Luczak, Partha S Banerjee, Lars S Maier, Xander H Wehrens, Joel L Pomerantz, Long-Sheng Song, Gerald W Hart, Mark E Anderson
Journal: Circulation (2017)

Diabetes mellitus and atrial fibrillation (AF) are major unsolved public health problems, and recent clinical studies show that diabetes is an independent risk factor for AF. However, the mechanism...
AB0651 THE INFLUENCE OF RITUXIMAB THERAPY ON THE DYNAMICS OF THE BASIC PARAMETERS AND ACTIVITY OF SYSTEMIC SCLEROSIS
Authors: Oxana Desinova, Mayya Starovoytova, Lidia P. Ananyeva, Liudmila Garzanova, Olga Koneva, Olga Ovsyannikova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and multi- organ involvements induced by overproduction of autoantibodiies by B cells. <h3>Objectives:</h3> To assess the influence of Rituximab (RTX) therapy on the dynamics of the basic parameters and activity of SSc during long-term follow-up. <h3>Methods:</h3> There were 90 SSc patients (pts) in the prospective study. 75% were women. 57% pts had diffuse SSc. SSc was confirmed aCR/EULAR criteria. The average duration of the disease was 5,8 years and of the study was 27 months. For the purpose of the analysis, a group of pts was selected that had no less than two evaluation points from 12 to 42 months and having received 2,9±1.1 g RТХ in average during such period. The examination included both routine clinical laboratory parameters and special research. We evaluated the modified Rodnan skin score (mRSS), forced vital capacity (FVC), diffusing capacity of carbon monoxide (DLCO), the Valentini Disease activity index, estimated glomerular filtration rate (eGFR) before and after completed RTX. All pts included in the study received treatment with vascular, anti-inflammatory and/or immunosuppressive medicines. The average dose of prednisolone was 11,8±4,4 mg/day. <h3>Results:</h3> In general, more than 90% pts demonstrated different kinds of improvements. A reliable improvement was documented based on a number of indicators, which reflect typical features of the disease. Thus, skin induration was reduced (skin score decreased), lung functional capacity increased (increase of FVC of more than 5%). The skin score was reliably decreased from 11,2±9,3 to 6,2 ±4,9 (р&lt;0.0001), FVC was increased from 76,9±19,9 to 84,7±20,9% (р&lt;0.0001), also the increase of DLCO from 46,3±18,3 to 47,8±16,9% from the proper amount was detected. The Valentini Disease activity index reliably reduced from 2,93±1,7 to 1,38±1,2 points (р&lt;0,0001). Under the RTX therapy, the decrease of glucocorticoids dose was insignificant, but statistically reliable. Thus, prednisolone dose reduction from 11,8±4,4 to 9,22±3,2 mg/day was achieved. Clinically insignificant but reliable decline of eGFR from 100,2±23 to 94,6±22 ml/min/1,73m2 was detected. <h3>Conclusion:</h3> Thus, RTX has a positive influence on the basic parameters of SSc, mainly on skin damage and lung functionality, reduces the general disease activity. The influence of the RTX on kidney function requires further long-term study. <h3>Disclosure of interests:</h3> None declared