tbuckley/cabot-search huggingface dataset:
PF251 GILTERITINIB PROLONGS SURVIVAL IN PATIENTS WITH FLT3‐MUTATED RELAPSED/REFRACTORY AML WHO HAVE COMMON AML CO‐MUTATIONS OR A HIGH FLT3‐ITD ALLELIC RATIO
Authors: M. Levis, A. Perl, G. Martinelli, J. Cortes, A. Neubauer, E. Berman, P. Montesinos, M. Baer, R. Larson, W.‐C. Chou, H. Yokoyama, C. Recher, S.‐S. Yoon, J. Hill, M. Rosales, C. Liu, E. Bahceci
Journal: HemaSphere (2019)

Background: Treatment with the FLT3 inhibitor, gilteritinib, resulted in superior response rates and overall survival compared with salvage chemotherapy in patients with FLT3 ‐mutated ( FLT3 mut+ ) relapsed/refractory AML in the phase 3 ADMIRAL study. Aims: We analyzed the impact of baseline co‐mutations and baseline FLT3 ‐internal tandem duplication (ITD) allelic ratio on achievement of complete remission/complete remission with partial hematologic recovery (CR/CRh) and overall survival. Methods: A total of 37 recurrently mutated genes in AML (Archer Core Myeloid Panel) were analyzed by next‐generation sequencing; the cutoff for co‐mutation positivity (co‐mut+) was ≥0.027. Baseline FLT3 ‐ITD allelic ratio ( FLT3 ‐ITD to FLT3 wild‐type DNA) was measured by the LeukoStrat ® CDx FLT3 Mutation Assay. The median FLT3 ‐ITD allelic ratio value of 0.77 was used to define high (≥0.77) vs low (&lt;0.77) FLT3 ‐ITD allelic ratio. Results: An analysis of 361 FLT3 mut+ patients identified four major co‐mutation cohorts, each with ≥10% of the patients: NPM1 (n = 173; 47.9%), DNMT3A (n = 115; 31.9%), DNMT3A/NPM1 (n = 86; 23.8%), and WT1 (n = 65; 18.0%). In addition, seven patients (1.9%) had all three co‐mutations (ie, NPM1 , DNMT3A , and WT1 ). The gilteritinib arm had superior CR/CRh rates and overall survival across all four major co‐mutation cohorts, with the greatest survival benefit in patients with DNMT3A/NPM1 co‐mut+ ( Table ). In FLT3‐ ITD allelic ratio analyses (n = 335), gilteritinib conferred longer overall survival than salvage chemotherapy in patients with a high or low FLT3 ‐ITD allelic ratio (gilteritinib: high FLT3 ‐ITD allelic ratio, 7.1 months vs low FLT3 ‐ITD allelic ratio, 10.6 months; salvage chemotherapy: high FLT3 ‐ITD allelic ratio, 4.3 months vs low FLT3 ‐ITD allelic ratio, 6.9 months). In both arms, overall survival was longer in the low FLT3 ‐ITD allelic ratio cohort than in the high FLT3 ‐ITD allelic ratio cohort, but the difference in the gilteritinib arm was not statistically significant (gilteritinib: hazard ratio = 1.341, P = 0.0712; salvage chemotherapy: hazard ratio = 2.01, P = 0.0021). Summary/Conclusion: The ADMIRAL trial shows that the clinical benefit of gilteritinib in FLT3 mut+ relapsed/refractory AML is maintained regardless of NPM1 , DNMT3A , DNMT3A / NPM1 , or WT1 co‐mut+ or high FLT3 ‐ITD allelic ratio. image
Abstract 19152: Development of Secondary Pulmonary Hypertension and Right Ventricular Dysfunction in a Mouse Model of Ischemic Heart Failure
Authors: Jennifer L Philip, Diana M Tabima, Timothy Hacker, Naomi C Chesler
Journal: Circulation (2017)

Introduction: Heart failure (HF) is the most common cause of pulmonary hypertension (PH). In HF, elevated pulmonary artery pressures are associated with increased morbidity and mortality. Many of t...
Abstract 18450: Cardioverter-defibrillator Does Not Improve Survival Among Patients With Non-ischemic Cardiomyopathy - Real Word Data From Evita-HF Registry
Authors: Clemens Jilek, Thorsten Lewalter, Matthias Pauschinger, Wolfgang von Scheidt, Lutz Frankenstein, Otmar Pfister, Rainer Hambrecht, Oliver Bruder, Johannes Brachmann, Andreas Hartmann, Ruth Strasser, Matthias Hochadel, Jochen Senges
Journal: Circulation (2017)

Introduction: The DANISH-Trial raised doubts about the effectiveness of primary prevention of sudden cardiac death by ICD-implantation among patients with non-ischemic heart failure. We sought to a...
AB1195 PREGNANCIES IN AUTOIMMNUNE DISEASES: EXPERIENCE OF TWO CENTERS IN CALI, COLOMBIA: 2011- 2018
Authors: álvaro Arbeláez-Cortés, Maria Andrea Moreno Salamanca, Diana Carolina Quintero González
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The outcome in pregnancy varies according to the rheumatic disease. <h3>Objectives</h3> To describe the pregnancies outcomes of women with rheumatic diseases at two reference centers in Cali, Colombia. <h3>Methods</h3> Descriptive study. Records of pregnant patients attended from August 2011 to December 2018 were reviewed. Thirty-nine patients were found, 11 without a defined rheumatic entity (10 with positive ANA only, and 1 with incomplete criteria for antiphospholipid syndrome), and 28 with an autoimmune rheumatic disease. A total of 41 pregnancies occurred (2 women with 2 pregnancies) and were chosen for the final analysis (Table). <h3>Results</h3> The mean gestational age at the first rheumatology visit was 16,8 ± 8,9. The mean age at the end of pregnancy was 29,5 ± 5,7 years. Only nine pregnancies were planned (34,6%). Among the patients with a defined autoimmune disease the diagnoses were: systemic lupus erythematosus (SLE) (12), rheumatoid arthritis (RA) (5), antiphospholipid syndrome (APS) (2), autoimmune hemolytic anemia (AHA) (2), juvenile idiopathic arthritis (JIA) (2), overlap syndrome (OS) (3: 2 SLE/SSc; 1 SLE/Sjögren's) mixed connective tissue disease (MCTD) (1) and undifferentiated connective tissue disease (UCTD) (1). There were 8 pregnancies exposed to teratogenic drugs (MTX 5, LEF 1, MMF 1, CYC 1): 2 ended in fetal loss and 1 had a congenital pneumonia. There were 27 full-term births, 37-40 weeks (wk); 8 preterm births, 23-36 wk (4 twins); 1 stillbirth, 26 wk; and 3 abortions (2 in the same mother). Seven patients had an active disease before pregnancy, 13 during pregnancy (7 SLE, 3 RA, 2 AIHA, 1 MCTD) and 13 during the puerperium (7 SLE, 4 AR, 1 AIJ, 1 EMTC). No maternal deaths, neonatal lupus or congenital heart block were documented in this series. Four patients did not require any medication. One woman received treatment for pulmonary tuberculosis, and other was on anti-retroviral treatment for HIV infection. At the last follow-up, 2 patients were still pregnant. <h3>Conclusion</h3> The outcome of rheumatic disease during pregnancy remains variable. It seems that SLE patients tend to be more active and flare more commonly than other patients. The documented complications were similar to those reported in the literature. <h3>References</h3> [1] Davutoğlu EA, Ozel A, Yılmaz N, Madazli R. Pregnancy outcome in 162 women with rheumatic diseases: experience of a university hospital in Turkey. Arch Gynecol Obstet. 2017 Dec;296(6):1079-1084. <h3>Disclosure of Interests</h3> None declared
AB1044 CYTOKINE PROFILE OF MACROPHAGE ACTIVATION SYNDROME ASSOCIATED WITH KAWASAKI DISEASE
Authors: Naoto Sakumura, Masaki Shimizu, Asumi Jinkawa, Hitoshi Irabu, Maiko Takakuwa, Natsumi Inoue, Mao Mizuta, Akihiro Yachie
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of childhood systemic inflammatory disorders. MAS occurs most often in children with systemic juvenile idiopathic arthritis and less commonly in children with Kawasaki disease (KD). <h3>Objectives</h3> Our study aimed to assess the kinetics of cytokine release and compare the accuracy of serum biomarkers for diagnosis of MAS, including neopterin, IL-18, IL-6 and soluble TNF receptor type I (sTNFR-I) and sTNFR-II levels, we analysed these levels in patients with KD, including those with MAS, and compared them to the clinical features of KD and MAS. <h3>Methods</h3> Serum neopterin, interleukin (IL)-18, IL-6 and soluble tumour necrosis factor receptor type I (sTNFR-I) and sTNFR-II levels were determined using enzyme-linked immunosorbent assay in 78 patients with KD, including five with MAS. Results were compared to the clinical features of MAS. <h3>Results</h3> Serum neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were significantly elevated in KD patients with MAS compared to those in the acute phase. Receiver operating characteristic curve analysis revealed areas under the curve and cutoff values of neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were 0.9750/30.0 nmol/L, 0.9813/1165 ng/mL, 0.9969/16,600 pg/mL and 0.9875/4.475, respectively. Serum sTNFR-II levels correlated positively with disease activity. <h3>Conclusion</h3> These findings indicate that interferon (IFN)–γ and tumour necrosis factor-α (TNF-α) are closely associated with the pathogenesis of MAS associated with KD. Serum sTNFR-II levels might be a useful marker to diagnose the transition to MAS. <h3>References</h3> [1] García-Pavón S, et al. J Pediatr Hematol Oncol 2017;39:445-451. [2] Shimizu M, et al. Cytokine 2018;108:168-172. <h3>Disclosure of Interests</h3> None declared
Meta-analysis of Aspirin for Primary Prevention of Cardiovascular Events
Authors: Nicholas L. Syn, Ian J. Y. Wee
Journal: JAMA (2019)

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Doctors’ early retirement triples in a decade
Authors: Tom Moberly
Journal: BMJ (2019)

The number of doctors taking early retirement has tripled in the past decade, NHS figures show.

From 2007-08 to 2018-19 the number of GPs and hospital doctors in England and Wales taking voluntary early retirement or retiring because of ill health rose from 386 to 1186. The average retirement age fell over this period, from 61 in 2007-08 to 59 in 2018-19.

Overall, the number of doctors retiring over the period rose by 7%, from 2359 to 2527. As more doctors have opted to retire …
PB1990 THE CHANGE OF BONE MARROW MICROENVIRONMENT OF SECONDARY POOR GRAFT FUNCTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AND ITS EFFECT ON PROGNOSIS
Authors: S. Liu, C. Ran, J. Li, X. Peng, X. Zhang, Y. Liu
Journal: HemaSphere (2019)

Background: Secondary poor graft functionis a serious life‐threatening complication after allogeneic hematopoietic stem cell transplantation, which pathogenesis, evolution and prognosis are still unclear. Aims: To explore the role of adhesion related indicators in secondary poor graft functionafter allogeneic hematopoietic stem cell transplantation Methods: In this study, clinical data and post‐transplantation status of 106 patients with hematological tumour who were enrolled in our center and underwent allo‐HSCT from Jan. 1, 2016 to Jan. 31, 2017 was counted.The patients were divided into good graft function (GGF) group and secondary poor graft function (sPGF) group according to the implantation status after transplantation. The differences of age, primary disease, stem cell source, HLA matching, sex matching, ABO blood group matching, degree of bone marrow hyperplasia before transplantation, recurrence rate and mortality between the two groups were compared.29 patients with sPGF after transplantation were selected as the experimental group while 29 patients with GGF were selected as the control group. Results: The changes of adhesion related indicators in the two groups were detected.There were no significant differences in age, primary disease, stem cell origin, HLA matching, sex matching, ABO blood group matching and the degree of bone marrow proliferation before transplantation between the two groups (P &gt; 0.05). The infection rate of CMV in sPGF group was significantly higher than that in GGF group, and the remission rate before transplantation in sPGF group was significantly lower than that in GGF group (P &lt; 0.05).Cox regression analysis showed that the survival rate of patients with sPGF after allo‐HSCT was significantly lower than that of patients without sPGF (P &lt; 0.05, HR = 3.598).The expression of CD44, CD29, ICAM‐1 and VCAM‐1 in sPGF group was not significantly different from that in control group (P &gt; 0.05), but the expression of CD105 was higher than that in control group, and the expression of Cx43 was lower than that in control group (P &lt; 0.05). Summary/Conclusion: We believe that the survival rate of patients with sPGF after allo‐HSCT will decrease significantly, and the occurrence of sPGF after transplantation may be related to the increase of CD105 expression and the decrease of Cx43 expression in bone marrow stromal cells before transplantation.
Magnetic Resonance Perfusion or Fractional Flow Reserve in Coronary Disease
Authors: Eike Nagel, John P. Greenwood, Gerry P. McCann, Nuno Bettencourt, Ajay M. Shah, Shazia T. Hussain, Divaka Perera, Sven Plein, Chiara Bucciarelli-Ducci, Matthias Paul, Mark A. Westwood, Michael Marber, Wolf-Stefan Richter, Valentina O. Puntmann, Carsten Schwenke, Jeanette Schulz-Menger, Rajiv Das, Joyce Wong, Derek J. Hausenloy, Henning Steen, Colin Berry
Journal: New England Journal of Medicine (2019)

In patients with stable angina, two strategies are often used to guide revascularization: one involves myocardial-perfusion cardiovascular magnetic resonance imaging (MRI), and the other involves invasive angiography and measurement of fractional flow reserve (FFR). Whether a cardiovascular MRI-based strategy is noninferior to an FFR-based strategy with respect to major adverse cardiac events has not been established.We performed an unblinded, multicenter, clinical-effectiveness trial by randomly assigning 918 patients with typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test to a cardiovascular MRI-based strategy or an FFR-based strategy. Revascularization was recommended for patients in the cardiovascular-MRI group with ischemia in at least 6% of the myocardium or in the FFR group with an FFR of 0.8 or less. The composite primary outcome was death, nonfatal myocardial infarction, or target-vessel revascularization within 1 year. The noninferiority margin was a risk difference of 6 percentage points.A total of 184 of 454 patients (40.5%) in the cardiovascular-MRI group and 213 of 464 patients (45.9%) in the FFR group met criteria to recommend revascularization (P = 0.11). Fewer patients in the cardiovascular-MRI group than in the FFR group underwent index revascularization (162 [35.7%] vs. 209 [45.0%], P = 0.005). The primary outcome occurred in 15 of 421 patients (3.6%) in the cardiovascular-MRI group and 16 of 430 patients (3.7%) in the FFR group (risk difference, -0.2 percentage points; 95% confidence interval, -2.7 to 2.4), findings that met the noninferiority threshold. The percentage of patients free from angina at 12 months did not differ significantly between the two groups (49.2% in the cardiovascular-MRI group and 43.8% in the FFR group, P = 0.21).Among patients with stable angina and risk factors for coronary artery disease, myocardial-perfusion cardiovascular MRI was associated with a lower incidence of coronary revascularization than FFR and was noninferior to FFR with respect to major adverse cardiac events. (Funded by the Guy's and St. Thomas' Biomedical Research Centre of the National Institute for Health Research and others; MR-INFORM ClinicalTrials.gov number, NCT01236807.).
Abstract 13935: The Effect of Enalapril on Cardiac Mechanics in the Pediatric Heart Network Infant Single Ventricle Trial: Insights Using Non-invasive Pressure-Volume Loop Analysis
Authors: Shahryar M Chowdhury, Jacob Strelow, Eric M Graham, Carolyn L Taylor, Andrew M Atz
Journal: Circulation (2017)

Introduction: Patients with single ventricle physiology who received enalapril in the Pediatric Heart Network (PHN) Infant Single Ventricle (ISV) Trial displayed no differences in heart failure out...
Response to Di Cosimo, Torri, and Porcu
Authors: Elisabeth Trapp, Wolfgang Janni, Christian Schindlbeck, Julia Jückstock, Ulrich Andergassen, Amelie deGregorio, Marianna Alunni-Fabbroni, Marie Tzschaschel, Arkadius Polasik, Julian G Koch, Thomas W P Friedl, Peter A Fasching, Lothar Haeberle, Tanja Fehm, Andreas Schneeweiss, Matthias W Beckmann, Klaus Pantel, Volkmar Mueller, Brigitte Rack, Christoph Scholz
Journal: JNCI Journal of the National Cancer Institute (2019)
Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner
Authors: Matthew Stephens, Pierre-Yves von der Weid
Journal: Gut Microbes (2019)

Patients presenting with Inflammatory bowel disease have been shown to exhibit an altered microbiome in both Crohn's disease and Ulcerative colitis. This shift in the microbial content led us to question whether several of these microbes are important in inflammatory processes present in these diseases and more specifically whether lipopolysaccharides from the gram-negative cell wall differentially stimulates resident cells. We, therefore, investigated the possible contribution of five major species of gram-negative bacteria found to be altered in presence during disease progression and evaluate their pathogenicity through LPS. We demonstrated that LPS from these different species had individual capacities to induce NF-κB and pro-inflammatory IL-8 production from HEK-TLR4 cells in a TLR4 dependent manner. Additional work using human intestinal colonic epithelial cell monolayers (Caco-2) demonstrated that the cells responded to the serotype specific LPS in a distinct manner, inducing many inflammatory mediators such as TNF-α and IL-10 in significantly altered proportions. Furthermore, the permeability of Caco-2 monolayers, as a test for their ability to alter intestinal permeability, was also differentially altered by the serotype specific LPS modulating trans-epithelial electrical resistance, small molecule movement, and tight junction integrity. Our results suggest that specific species of bacteria may be potentiating the pathogenesis of IBD and chronic inflammatory diseases through their serotype specific LPS responses.
Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk
Authors: Yakir A. Reshef, Hilary K. Finucane, David R. Kelley, Alexander Gusev, Dylan Kotliar, Jacob C. Ulirsch, Farhad Hormozdiari, Joseph Nasser, Luke O’Connor, Bryce van de Geijn, Po-Ru Loh, Sharon R. Grossman, Gaurav Bhatia, Steven Gazal, Pier Francesco Palamara, Luca Pinello, Nick Patterson, Ryan P. Adams, Alkes L Price
Journal: Nature Genetics (2018)
PB1922 PONATINIB INDUCES A SUSTAINED DEEP MOLECULAR RESPONSE IN A CHRONIC MYELOID LEUKAEMIA PATIENT WITH AN EARLY RELAPSE WITH A T315I MUTATION FOLLOWING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: N. Cerveira, R.B. Ferreira, S. Bizarro, C. Correira, L. Torres, S. Lisboa, J. Vieira, R. Santos, F. Campilho, C. Pinho Vaz, L. Leite, M. Teixeira, A. Campos
Journal: HemaSphere (2019)

Please indicate where the abstract has been published before: BMC Cancer. Background: Atypical BCR‐ABL1 transcripts are detected in less than 5% of patients diagnosed with chronic myeloid leukaemia (CML), of which e19a2 is the most frequently observed, with breakpoints in the micro breakpoint cluster region (μ‐BCR) and coding for the p230 BCR‐ABL1 protein. p230 CML is associated with various clinical presentations and courses with variable responses to first‐line imatinib. Aims: In the present study we describe in detail the clinical history of a CML patient with a rare e19a2 BCR‐ABL1 transcript who has failed several lines of targeted therapy with tyrosine kinase inhibitors and relapsed after allogeneic hematopoietic stem cell transplantation. Methods: Detailed characterization of the patient's clinical history including therapeutic approach and cytogenetic and molecular analysis. Results: Here we report a case a CML patient with imatinib resistance due to an E255 V mutation, followed by an early post‐transplant relapse with a T315I mutation that achieved a persistent negative deep molecular response (MR 5.0 ) after treatment with single‐agent ponatinib. Using CastPCR, we could trace back the presence of the T315I mutation to all the RNA samples up to the detection of T315 mutation by Sanger sequencing shortly after allogeneic hematopoietic stem cell transplantation. Summary/Conclusion: This case illustrates the major interest of Ponatinib as a valid treatment option for e19a2 CML patients who present a T315I mutation following relapse after allogeneic hematopoietic stem cell transplantation. image
AB0529 SICCA SYNDROME DURING CHRONIC HEPATITIS C: PREVALENCE AND CHARACTERISTICS
Authors: KCHIR hela, Ons Gharbi, Dhilel Issaoui, Dhouha Cherif, Faten Limaiem, Mejda Essid, Nadia Maamouri
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The prevalence of Sicca Syndrome (SS) in patients with Chronic Hepatitis C (CHC) ranges from 5% to 33%. A link between hepatitis C virus (HCV) and SS was evoked given the strong association of these two pathologies with mixed cryoglobulinemia (MC) on one hand and with the salivary tropism of HCV on the other hand. <h3>Objectives:</h3> To study the prevalence and the characteristics of Sicca Syndrome during CHC. <h3>Methods:</h3> All patients suffering from CHC followed over a period of 11 years (2002 – 2012) were retrospectively included. Only patients having clinical SS (xerostomia and/or xerophthalmia) were selected. We have analyzed all data concerning the patient, the hepatitis and the SS. <h3>Results:</h3> Two hundred and four patients affected by CHC were included. A clinical SS was found in 17 patients (8.39%). There were 15 women and 2 men with an average age of 45.6 years. A High viral load and an advanced hepatic fibrosis were respectively found in 94 and 88% of cases. Cryoglobulinemia and antinuclear antibodies were found in 37.5% and 53% of patients, respectively. Four patients (3 women and 1 man) had also presented the criteria of Sjogren Syndrome. Their average age was 47 years. MC was positive in all 4 patients whereas anti-SSA and anti-SSB were absent in the 4 patients. Biopsy of accessory salivary glands revealed the presence of a grade 4 lymphocytic sialadenitis according to the Chisholm and Masson classification in 3 patients, while the remaining case had a lymphocyte grade 2 sialadenitis. The evaluation of hepatic fibrosis did not reveal cirrhosis in the 4 cases. <h3>Conclusion:</h3> The prevalence of Sicca syndrome during hepatitis C is estimated at 8% in our study. It was mainly reported in women with perimenopausal age and seems to be associated with cryoglobulinemia, a high viral load and and an advanced fibrosis. <h3>Disclosure of Interests:</h3> None declared