tbuckley/cabot-search huggingface dataset:
Myeloproliferative neoplasm with eosinophilia and T-lymphoblastic lymphoma with ETV6–LYN gene fusion
Authors: N Telford, S Alexander, O J McGinn, M Williams, K M Wood, A Bloor, V Saha
Journal: Blood Cancer Journal (2016)

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal haematopoietic stem cell disorders characterised by proliferation and maturation of different myeloid cell lineages. Classical MPNs are largely characterised by somatic mutation of JAK2, CALR or occasionally MPL genes.1, 2 MPNs can develop from chromosomal translocations forming gene fusions, involving constitutive activation and aberrant expression of tyrosine kinase (TK). Other than the BCR-ABL1 rearrangement in chronic myeloid leukaemia, gene fusions involving TK proto-oncogenes are rare in MPN but when detected, provide compelling disease-specific therapeutic targets.3 Myeloproliferative and lymphoid neoplasms with eosinophilia and specific TK gene fusions are a recently described, rare entity of clinical significance due to varying responsiveness to tyrosine kinase inhibitors (TKIs).4 The three cytogenetic categories identified, involving fusions of PDGFRA, PDGFRB or FGFR1 with different partner genes, are thought to affect a pluripotent stem cell and have variable presentation as MPN with eosinophilia, occasionally with a T-lymphoid disease component. Excellent response rates and long-term clinical outcomes have been reported with abnormalities of PDGFRA and PDGFRB treated with imatinib, whereas disorders with FGFR1 and JAK2 gene fusions are resistant to imatinib and other TKIs. We present a case of a disease fitting within this clinical and haematological spectrum, with a chromosomal rearrangement between chromosomes 8 and 12, bearing ETV6–LYN gene fusion.
SAT0383 The Functionl Impact of Asymptomatic Axial Involvement in Psoriatic Arthritis
Authors: C. Pana, A.-M. Ramazan, L. Muflic, M. Suta
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Spondylitis associated with peripheral psoriatic arthritis occurs in 40% to 70% of the patients, depending on whether or not radiographs are taken (1). Careful clinical and radiologic assessment, however, reveals involvement of the axial spine in 20% to 40% of cases, increasing to as many as 51% at long-term follow-up (2). Involvement of the sacroiliac joints can be symmetric or asymmetric. During follow-up,although the radiographic changes in the spine tend to progress,spinal mobility is preserved or improves, and this form of spinal disease carries a better prognosis than pure ankylosing spondylitis.(2) Queiro et al had reported asymptomatic spondilitis in 20% of patients with psoriatic arthritis (PA), and Taylor et al had reported a higher frequency of radiological lesions without symptoms (3,4,5). <h3>Objectives</h3> To identify the functional impact of asymtomatic axial involvement in patients with PA <h3>Methods</h3> 88 PA patients (59.1%, women, mean age 55.53±11.06 years, mean of PA duration about 12.49±11.61 years) were included. Patients were assessed as followings: demographical, medical history, a clinical assessment for joint disease (activity score like BASDAI, functional score like BASFI, mobility score like BASMI and classical indices) and an radiological assessment for progression (sacroiliac and vertebral according BASRI score).We have considered axial involvement the presence of sacroiliitis and/or vertebral spondylitis. <h3>Results</h3> We had noticed asymptomatic axial involvement in 13.63% (12 patients) patients, been 83% of them with sacroiliitis graded 3 and 4. Regarding functionality, BASFI had a mean about 3.77±2.33 (p=0.006) versus 6.29±2.71 in patients with lumbar pain and PA. Mobility is clearly better in patients with asymptomatic sacroiliitis: BASMI score (1±1.41, 3.23±3.01, p=0.008), Schober index (4.33±1.48, 3.35±2.32, p=0.003), chest expansion index (2.54±0.96, 2.40±1.38, p=NS), menton-stern index (2.5±1.5, 3.82±2.09, p=0.043). The activity score BASDAI had differences in groups with or without spinal pain (5.91±2.4, 4.16±1.9, p=0.028). The radiological score BASRI had any significant differences between groups (5.54±3.91, 5.64±3.19, p=NS). <h3>Conclusions</h3> Even asymptomatic, axial involvement is present and give them quiet spinal disability and severe radiological progression <h3>References</h3> Ritchlin C, Psoriatic and Reactive Arthritis, 2007. Hochberg, Rheumatology, 2011. Gladman DD et al, PA-an analysis of 220 patents, Q J Med 1987; 62:127-141. Gladman DD, Natural history of PA, Baillieres Clin Rheumatol 1994; 8: 379-394. Gladman DD et al,Psoriatic spondyloarthropathy in men and women: a clinical, radiographic and HLA study, Clin Invest Med 1992; 15: 371-375. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4389
Perioperative Antibiotic Prophylaxis for Herniorrhaphy and Breast Surgery
Authors: R Platt, D F Zaleznik, C C Hopkins, E P Dellinger, A W Karchmer, C S Bryan, J F Burke, M A Wikler, S K Marino, K F Holbrook
Journal: New England Journal of Medicine (1990)

We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast, including excision of a breast mass, mastectomy, reduction mammoplasty, and axillary-node dissection. The prophylactic regimen was a single dose of cefonicid (1 g intravenously) administered approximately half an hour before surgery. The patients were followed up for four to six weeks after surgery. Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made.
612 EARLY TIPS IN PATIENTS WITH ACUTE VARICEAL BLEEDING AND THE EFFECT ON THIRTY DAY AND SIX MONTH MORTALITY RATES – A SINGLE CENTRE EXPERIENCE
Authors: E. Britton, S. Mahoney, S. Powell, R. McWilliams, U. Shaikh, A. Healy, J. Evans, P. Rowlands, P. Richardson
Journal: Journal of Hepatology (2013)
The Clinical Spectrum of Familial Hemiplegic Migraine Associated with Mutations in a Neuronal Calcium Channel
Authors: Anne Ducros, Christian Denier, Anne Joutel, Michaëlle Cecillon, Christelle Lescoat, Katayoun Vahedi, Françoise Darcel, Eric Vicaut, Marie-Germaine Bousser, Elisabeth Tournier-Lasserve
Journal: New England Journal of Medicine (2001)

Familial hemiplegic migraine, an autosomal dominant disorder characterized by attacks of transient hemiparesis followed by a migraine headache, is divided into pure familial hemiplegic migraine (affecting 80 percent of families) and familial hemiplegic migraine with permanent cerebellar signs (affecting 20 percent of families). Mutations in CACNA1A, which encodes a neuronal calcium channel, are present in 50 percent of families with hemiplegic migraine, including all those with cerebellar signs. We studied the various clinical manifestations associated with mutations in CACNA1A in 28 families with hemiplegic migraine with and without cerebellar signs.
Phase IB study of cabozantinib in patients with relapsed and/or refractory multiple myeloma
Authors: Nikoletta Lendvai, Andrew J. Yee, Ioanna Tsakos, Aeri Alexander, Sean M. Devlin, Hani Hassoun, Neha Korde, Alexander M. Lesokhin, Heather Landau, Sham Mailankody, Guenther Koehne, David J. Chung, Ola Landgren, Noopur S. Raje, Sergio Giralt
Journal: Blood (2016)
Identification of novel genetic risk loci determine fetal outcome in congenital heart block
Authors: Sabrina Görgen, Bo Ding, Stina Salomonsson, Lars Klareskog, Anders Hamsten, Jan Hillert, Lars Alfredsson, Tomas Olsson, Ingrid Kockum, Marie Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Congenital heart block (CHB) is a life threatening heart condition where the fetal atrioventricular conduction system is disrupted. The block may occur during fetal development after placental transfer of autoantibodies from Ro/SSA positive mothers. The association with maternal Ro/SSA antibodies is well established; however the recurrence risk is only 11-20% despite persisting autoantibodies in the mother, suggesting that additional factors other than the maternal autoantibodies determine disease development and fetal outcome. We hypothesized that the fetal genetic composition is a major factor influencing susceptibility to CHB, and therefore conducted a genome-wide association study to map potential genetic risk loci involved in CHB pathogenesis. <h3>Methods</h3> Genotyping of 561,490 SNP markers was accomplished in DNA samples from 389 individuals of 104 Swedish Caucasian families with at least one case of congenital heart block and a maternal serum positive for Ro/SSA autoantibodies. A family-based association analysis was performed using the transmission disequilibrium test (PLINK). The Cochran–Mantel–Haenszel statistical test was used to investigate SNP associations with CHB in index cases (n=88) compared to Swedish Caucasian population-based healthy controls (n=1710). <h3>Results</h3> A family-based analysis (n=348) revealed 37 SNP markers with a p value of P<sub>GWAS family</sub> ≤9.88×10<sup>−5</sup> (OR 0.18–6.50) associated to congenital heart block. In a case-control analysis between the index cases and population-based healthy controls 6 of the 37 SNP markers were confirmed. The CHB risk loci are located at the chromosomal positions 1p31.3, 2q35 and 3p25.1 and genes encoded within these regions are involved in cellular stress responses, energy metabolism and tissue repair. <h3>Conclusion</h3> Our study identifies three novel genetic risk loci associated with development of CHB after exposure to maternal Ro/SSA autoantibodies. Functional exploration of the genes encoded within these risk loci will help to shed light on the cellular mechanisms underlying CHB pathogenesis.
Clozapine-Induced Agranulocytosis -- Incidence and Risk Factors in the United States
Authors: Jose Ma. J. Alvir, Jeffrey A. Lieberman, Allan Z. Safferman, Jeffrey L. Schwimmer, John A. Schaaf
Journal: New England Journal of Medicine (1993)

Clozapine is an atypical antipsychotic agent that is more effective than standard neuroleptic drugs in the treatment of patients with refractory schizophrenia. Unlike classic neuroleptic agents, clozapine is not associated with the development of acute extrapyramidal symptoms or tardive dyskinesia. The main factor limiting its use is the risk of potentially fatal agranulocytosis, estimated to occur in 1 to 2 percent of treated patients. After clozapine was approved by the Food and Drug Administration, it became available for marketing in the United States in February 1990 only as part of a special surveillance system (the Clozaril Patient Management System, or CPMS), in which a weekly white-cell count was required for the patient to receive a supply of the drug.
AB1296 Reliability of the different ultrasonographic features in knee osteoarthritis
Authors: S. Slimani, A. Haddouche, A. Ladjouze-Rezig
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous studies on ultrasonography in the diagnosis of knee osteoarthritis have described different features seen in painful osteoarthritic knees. We statistically evaluated the diagnostic values of these features as compared to healthy controls. <h3>Methods</h3> We prospectively performed ultrasonography on 43 painful osteoarthritic knees of 25 subjects, comparing them with 40 knees of 20 sex and gender-matched healthy subjects, using a linear probe (Shimadzu SDU 1200; 10-5 MHz). Comparisons between the two groups were carried-out using Mann-Whitney U test for continuous variables and Chi-square test or Fisher exact test for relevant categorical variables. Relative risks were also calculated. <h3>Results</h3> The mean age of patients was 52.1±5.3 years, 60% women. Abnormal features were found in 100% cases and 27% controls (p&lt;0.0001; RR=3.6, 95% CI: 2.2-6.0). The most relevant features were the presence of joint effusion &gt;2mm (79% Vs 12%; p&lt;0.0001; RR=6.3, 95% CI: 2.7-14.5), joint effusion’s height (10.4 mm Vs 0.8 mm; p&lt;0.0001), the presence of synovial thickening (46.5% Vs 10%; p&lt;0.0001; RR=4.6, 95% CI: 1.7-12.5) and the presence of at least one femoro-tibial osteophyte (100% Vs 12%; p&lt;0.0001; RR=8; 95% CI: 3.5-18.2). Cartilage thickness (inter-condylar: 2.3mm Vs 2.2mm; p=0.233), as well as the presence of a Power Doppler signal (4.6% Vs 0%; p=0.265) did not statistically differ between groups. <h3>Conclusions</h3> Joint effusion, synovial thickness and femoro-tibial osteophytes are the most useful features for an ultrasonographic diagnosis for knee osteoarthritis. There is a need to develop an ultrasonographic scoring system for diagnosing knee osteoarthritis and assessing its severity and prognosis. <h3>Disclosure of Interest</h3> None Declared
Abstract A33: A whole genome RNAi screen identifies BRD7 and BAF180 as p53 regulators required for senescence
Authors: Anna E. Burrows, Agata Smogorzewska, Stephen J. Elledge
Journal: Cancer Research (2011)

Abstract Multiple tumor-suppressor mechanisms exist to promote genomic stability. One such mechanism is cellular senescence. In response to DNA damage and oncogenic stimuli, the senescence program, including the p53 and Rb pathways, is activated to prevent the proliferation of damaged cells and their potential oncogenic transformation. We are performing a pooled whole genome shRNA screen in primary human fibroblasts to identify novel components of the senescence machinery. In addition to many known senescence regulators including cell cycle and DNA damage response factors, we have also uncovered many genes of unknown function. From this screen we have identified SWI/SNF components BRD7 and BAF180 as novel regulators of replicative and oncogene-induced senescence. Both BRD7 and BAF180 are required for p53 transcriptional activity toward a subset of target genes including p21, and BRD7 physically interacts with p53. Overexpression of BRD7 induces premature senescence and p21 expression, highlighting its regulatory role in this pathway. We also show that BRD7 is required for expression of p21 in p53-independent contexts, such as in response to TGF-β and 1α,25(OH)2D3 (vitamin D) in epithelial cells. Lastly, BRD7 and BAF180 are deletion targets in human cancer, suggesting that their loss may provide additional mechanisms to antagonize p53 function in cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A33.
ELEVATED LEVELS OF OXIDIZED PHOSPHOLIPIDS ON APOLIPOPROTEIN B-100 PREDICT RECURRENT CEREBROVASCULAR EVENTS: A STROKE PREVENTION BY AGGRESSIVE REDUCTION IN CHOLESTEROL LEVELS (SPARCL) SUBSTUDY
Authors: Young Sup Byun, Xiaohong Yang, Bao Weihang, David DeMicco, Rachel Laskey, Joseph Witztum, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2015)
AB1152-HPR Fatigue in Patients with Chronic Widespread Pain Participating in Multidisciplinary Rehabilitation Treatment: A Prospective Cohort Study
Authors: A. De Rooij, M. Van Der Leeden, M.R. de Boer, M.P. Steultjens, J. Dekker, L. Roorda
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In addition to pain, fatigue is a prominent symptom in patients with chronic widespread pain (CWP). The factors and mechanisms of change associated with (improvement in) fatigue in multidisciplinary rehabilitation treatment are unclear. <h3>Objectives</h3> To explore the associations between (improvement in) fatigue and (improvement in) clinical and cognitive factors in patients with chronic widespread pain (CWP), participating in multidisciplinary rehabilitation treatment. <h3>Methods</h3> Data were used from baseline, 6 and 18 months of follow-up during a prospective cohort study of 120 CWP patients who completed multidisciplinary rehabilitation treatment. Cross-sectional and longitudinal relationships were analyzed between fatigue, clinical (i.e. pain, interference of pain and depression) and pain related cognitive factors (i.e. negative emotional cognitions, active cognitive coping, and control and chronicity beliefs). <h3>Results</h3> Higher levels of pain, interference of pain, depression, negative emotional cognitions, and negative control and chronicity beliefs were associated with a higher level of fatigue. Improvement in depression was related to improvement in fatigue. <h3>Conclusions</h3> In CWP patients, worse clinical status, and dysfunctional pain related cognitions are associated with a higher level of fatigue. Our results suggest that improvement in depression might be a mechanism of improvement in fatigue. Furthermore, improvement in fatigue seems to be independent of improvement in pain related cognitions. Targeting fatigue in multidisciplinary pain treatment may need specific strategies. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4572
Hirsutism, Polycystic Ovarian Disease, and Ovarian 17-Ketosteroid Reductase Deficiency
Authors: Songya Pang, Barney Softness, William J. Sweeney, Maria I. New
Journal: New England Journal of Medicine (1987)

We studied an 18-year-old woman with progressive hirsutism, secondary amenorrhea, and polycystic ovarian disease. Excess androstenedione was secreted by the ovaries, most likely because of a genetic deficiency of ovarian 17-ketosteroid reductase, the enzyme that converts androstenedione to testosterone. Markedly elevated basal plasma levels of androstenedione, estrone, and testosterone were regulated by gonadotropin but not by ACTH. The rate of androstenedione production in the patient's blood at base line and after administration of dexamethasone was very high (10.0 to 11.6 mg per day; value in control women with hirsutism, less than 4.1 mg per day), whereas her blood production of testosterone was 0.64 to 0.7 mg per day, similar to or higher than that in control women with hirsutism. The fractional blood conversion ratio of androstenedione to testosterone was normal (5.6 percent). Thus, 88 to 93 percent of the testosterone in the blood was derived from the peripheral conversion of androstenedione, and very little testosterone was secreted by the ovaries. These in vivo biochemical data suggest that the patient had a deficiency of ovarian 17-ketosteroid reductase activity but normal pubertal activity. The patient's two younger sisters with peripubertal symptoms of androgen excess also had elevated serum levels of androstenedione. We propose that the increased secretion of androstenedione in the three siblings in this family was probably due to a genetic deficiency of ovarian 17-ketosteroid reductase.
SAT0557 Diagnostic Performance of Rheumatoid Factor and Anti-CCP Antibody for Detecting Undiagnosed Rheumatoid Arthritis in Annual Health Check
Authors: R. Rokutanda, M. Kishimoto, K. Yamaguchi, H. Shimizu, Y. Suyama, Y. Ohara, Y. Haji, C. Min, A. Takeda, Y. Matsui, T. Matsubara, K. Nishioka, M. Okada
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There have been few studies regarding the way to pick up undiagnosed rheumatoid arthritis (RA) in annual health check examination. <h3>Objectives</h3> The purpose of this study it to evaluate the usefulness of rheumatoid factor (RF) and anti-CCP antibody (ACPA) to detect undiagnosed RA in annual health check. <h3>Methods</h3> During the period from January 2008 to September 2012, we checked RF in all the patients who visited St. Luke's International Hospital Center for Preventive Medicine for annual health examinations. Patients who had positive RF with joint symptom and who have highly positive RF (3 times higher than upper limit of normal), with or without joint symptom, are encouraged to be checked ACPA. We retrospectively extracted all the patients who had positive RF, and evaluate the number of newly diagnosed RA and diagnostic utility of ACPA in RF positive population. <h3>Results</h3> A total of 34,696 patients were checked RF, and 2210 patients showed positive RF during the study period. Among them, ACPA was checked in 629 patients, and 74 patients had positive result. All the patients who underwent ACPA test were examined by rheumatologist at least once. The diagnosis of RA was made significantly frequent in ACPA positive group (26/74 patients, 35.1%) than in ACPA negative group (19/555 patients, 3.4%, p&lt;0.001) after health check. The sensitivity and specificity of ACPA in this population were 57.8% and 90.2%, respectively. <h3>Conclusions</h3> ACPA showed high specificity for diagnosing RA in RF positive population. The combination of RF and ACPA screening in health check can be useful for detecting undiagnosed RA. <h3>Disclosure of Interest</h3> None Declared
TRANSCATHETER VERSUS SURGICAL AORTIC VALVE REPLACEMENT IN END STAGE RENAL DISEASE: AN ANALYSIS OF THE NATIONWIDE INPATIENT SAMPLE DATABASE
Authors: Anna Koulova, Saurav Chatterjee, Partha Sardar, Jay Giri, James DiNicolantonio, Giuseppe Biondi-Zoccai, Dmitry Feldman, Sripal Bangalore
Journal: Journal of the American College of Cardiology (2015)
THU0352 Long-Term Safety and Efficacy of Golimumab in the Treatment of Ankylosing Spondylitis: Results Through 5 Years of the Go-Raise Trial
Authors: A. Deodhar, J. Braun, R. Inman, D. van der Heijde, Y. Zhou, B. Hsu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Golimumab(GLM) has demonstrated significant and sustained clinical efficacy and an acceptable safety profile through 2yrs of the phase 3, randomized, PBO-controlled, GO-RAISE study in pts with ankylosing spondylitis (AS). <h3>Objectives</h3> To evaluate GLM safety/efficacy in AS pts receiving GLM50mg and/or 100mg through 5yrs. <h3>Methods</h3> 356pts with AS were randomized to SC PBO, GLM50mg, or GLM100mg q4w. At wk16, pts with inadequate response early escaped (EE) with blinded dose adjustments (PBO→GLM50mg, GLM50mg→ 100mg). At wk24, pts still receiving PBO crossed over to GLM50mg. Pts continued double-blind treatment through wk100. The long-term extension started with the wk104 GLM injection. Pts received GLM q4w for ~5yrs (final injection at wk252). After unblinding at wk104 and at the investigator's discretion, pts receiving GLM50mg could increase their dose to 100mg; pts receiving GLM100mg could decrease dose to 50mg; concomitant DMARD, corticosteroid, and NSAID therapy could be adjusted. <h3>Results</h3> Among 356 randomized pts, 254 pts continued treatment through wk252; 242 completed the safety follow-up through wk268. 101 pts withdrew (33 [9.3%] due to AEs, 35 [9.8%] lack of efficacy, 11 [3.1%] lost to follow-up, 22 [6.2%] for other reasons); 1pt was untreated. Reductions in AS-related signs/symptoms and improvements in physical function and range of motion observed at wk14 (primary endpoint visit; previously reported) were maintained through 5yrs (Table). Serious AEs were reported for 17.1% of GLM50mg, 24.7% of GLM100mg, and 22.0% of all GLM-treated pts. One pt died (GLM50mg, B cell lymphoma after 3yrs in the study, followed by pancreatic cancer). <h3>Conclusions</h3> In pts with active AS, SC GLM50 and 100mg q4w improved AS signs/symptoms, physical function, and range of motion and demonstrated an acceptable safety profile that was consistent with previously reported results for GLM through wk160 and with other anti-TNF biologics. There were no differences between the two GLM dosages. <h3>Disclosure of Interest</h3> A. Deodhar Grant/research support from: Janssen R&amp;D, LLC, J. Braun Grant/research support from: Janssen R&amp;D, LLC, R. Inman Grant/research support from: Janssen R&amp;D, LLC, D. van der Heijde Grant/research support from: Janssen R&amp;D, LLC, Y. Zhou Shareholder of: Johnson &amp; Johnson, Employee of: Janssen R&amp;D, LLC, B. Hsu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen R&amp;D, LLC
876 SOLUBLE SERUM CD81 IS ELEVATED IN PATIENTS WITH CHRONIC HEPATITIS C AND CORRELATES WITH ALANINE AMINOTRANSFERASE SERUM ACTIVITY
Authors: M.-W. Welker, D. Reichert, S. Süsser, C. Sarrazin, Y. Martinez, E. Herrmann, S. Zeuzem, A. Piiper, B. Kronenberger
Journal: Journal of Hepatology (2012)