tbuckley/cabot-search huggingface dataset:
The International Scoring System (ISS) for Multiple Myeloma Remains a Robust Prognostic Tool Independently of Patients' Renal Function
Authors: Meletios A. Dimopoulos, Efstathios Kastritis, Marie-Christine Kyrtsonis, John Meletis, Eurydiki Michalis, Panagiotis Repoussis, Konstantinos Tsatalas, Michael Michael, Anastasia Pouli, Zafiris Kartasis, Ekaterini Stefanoudaki, Michael Voulgarelis, Sosana Delimpasi, Eirini Katodritou, Argiris Symeonidis, Maria Gavriatopoulou, Efstathios Koulieris, Dimitra Gika, Athanasios Zomas, Paraskevi Roussou, Nikolaos Anagnostopoulos, Theofanis Economopoulos, Konstantinos Konstantopoulos, Agapi Parcharidou, Konstantinos Zervas, Evangelos Terpos
Journal: Blood (2010)
Both Tadalafil and Dexamethasone May Reduce the Incidence of High-Altitude Pulmonary Edema
Authors: Marco Maggiorini, Hans-Peter Brunner-La Rocca, Simon Peth, Manuel Fischler, Thomas Böhm, Alain Bernheim, Stefanie Kiencke, Konrad E. Bloch, Christoph Dehnert, Robert Naeije, Thomas Lehmann, Peter Bärtsch, Heimo Mairbäurl
Journal: Annals of Internal Medicine (2006)

In this double-blind trial, 29 adults with a history of high-altitude pulmonary edema (HAPE) were randomly assigned to receive prophylactic tadalafil, dexamethasone, or placebo during a 24-hour asc...
Experimental Lung Injury Reduces Krüppel-like Factor 2 to Increase Endothelial Permeability via Regulation of RAPGEF3–Rac1 Signaling
Authors: Ru-Ting Huang, David Wu, Angelo Meliton, Myung-Jin Oh, Matthew Krause, Joyce A. Lloyd, Recep Nigdelioglu, Robert B. Hamanaka, Mukesh K. Jain, Anna Birukova, John P. Kress, Konstantin G. Birukov, Gökhan M. Mutlu, Yun Fang
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Acute respiratory distress syndrome (ARDS) is caused by widespread endothelial barrier disruption and uncontrolled cytokine storm. Genome-wide association studies (GWAS) have linked multiple genes to ARDS. Although mechanosensitive transcription factor Krüppel-like factor 2 (KLF2) is a major regulator of endothelial function, its role in regulating pulmonary vascular integrity in lung injury and ARDS-associated GWAS genes remains poorly understood.To examine KLF2 expression in multiple animal models of acute lung injury and further elucidate the KLF2-mediated pathways involved in endothelial barrier disruption and cytokine storm in experimental lung injury.Animal and in vitro models of acute lung injury were used to characterize KLF2 expression and its downstream effects responding to influenza A virus (A/WSN/33 [H1N1]), tumor necrosis factor-α, LPS, mechanical stretch/ventilation, or microvascular flow. KLF2 manipulation, permeability measurements, small GTPase activity, luciferase assays, chromatin immunoprecipitation assays, and network analyses were used to determine the mechanistic roles of KLF2 in regulating endothelial monolayer integrity, ARDS-associated GWAS genes, and lung pathophysiology.KLF2 is significantly reduced in several animal models of acute lung injury. Microvascular endothelial KLF2 is significantly induced by capillary flow but reduced by pathologic cyclic stretch and inflammatory stimuli. KLF2 is a novel activator of small GTPase Ras-related C3 botulinum toxin substrate 1 by transcriptionally controlling Rap guanine nucleotide exchange factor 3/exchange factor directly activated by cyclic adenosine monophosphate, which maintains vascular integrity. KLF2 regulates multiple ARDS GWAS genes related to cytokine storm, oxidation, and coagulation in lung microvascular endothelium. KLF2 overexpression ameliorates LPS-induced lung injury in mice.Disruption of endothelial KLF2 results in dysregulation of lung microvascular homeostasis and contributes to lung pathology in ARDS.
A Placebo-Controlled Phase III Trial of Patient-Specific Immunotherapy with Mitumprotimut-T (ID-KLH) and GM-CSF Following Rituximab in Patients with CD20+ Follicular Lymphoma
Authors: Arnold S. Freedman, Sattva Neelapu, Craig R Nichols, Michael Robertson, Benjamin Djulbegovic, Jane N. Winter, Daniel Gold, John Bender, Morgan Stewart, Richard G. Ghalie, Paul A. Hamlin
Journal: Blood (2008)
PWE-084 Dysphagia in Patients with Non-Erosive Gatro-Oesophageal Reflux Disease: Abstract PWE-084 Table 1
Authors: K Nikaki, J Ooi, YS Soozandehfar, P Woodland, D Sifrim
Journal: Gut (2016)

<h3>Introduction</h3> Dysphagia is commonly reported by patients with NERD.<sup>1</sup> In the absence of mechanical obstruction or erosions, the mechanism underlying dysphagia in NERD is unclear. Impaired oesophageal motility with delayed bolus clearance, increased resistance at the OGJ or impairment of mucosal integrity could potentially underlie this symptom. The aim of this study was to evaluate these potential causes of dysphagia in NERD patients. <h3>Methods</h3> All adult patients, presenting to the Upper GI Physiology unit between January 2014 and October 2015, with typical GERD symptoms, normal OGD, acid exposure time &gt; 4.2%, no major manometric abnormalities and no structural, systemic or neurologic abnormalities were included. A composite dysphagia score was prospectively recorded (0–45). Motility was evaluated using HRM and Chicago classification 2015. Bolus clearance was assessed on 24 h pH-MII using bolus exposure time and post-reflux peristaltic wave (PSPW) score. Mucosal integrity was evaluated using Mean Nocturnal Baseline Impedance (MNBI). <h3>Results</h3> Out of the 76 eligible patients, 17 patients (8 M:9 F) with typical NERD and dysphagia symptoms (Group A) and 26 patients (15 M:11 F) with NERD only symptoms (Group B) fulfilled the inclusion criteria. Mean age for both groups was 49 years. Acid exposure time and number of reflux episodes between groups were similar (NS). The median composite dysphagia score for Group A was 19.5 (range 3.5–45). Minor oesophageal motility abnormalities were identified in 10/17 patients from Group A and 12/26 patients from Group B (P &gt; 0.05). The median IRP was 6 mmHg in group A and 7 mmHg in group B (NS). There was no statistically significant difference in the bolus exposure time and PSPW index. Mucosal integrity evaluated with baseline impedance (MNBI) was slightly low in the distal oesophagus, without difference between groups. MNBI in the proximal oesophagus was normal and not different between groups (Table). <h3>Conclusion</h3> 40% of NERD patients reported dysphagia; majority reporting moderately severe symptoms. Impairment of oesophageal motility, bolus clearance and mucosal integrity do not seem to explain the pathophysiology of dysphagia in these patients. Esophageal hypersensitivity to mechanical stimulation and/or hypervigilance remained as potential causes of dysphagia in patients with NERD. <h3>Reference</h3> 1 Locke 3rd GR, et al. Prevalence and clinical spectrum of gastroesophageal reflux: A population-based study in Olmsted County, Minnesota. <i>Gastroenterology</i> 1997;<b>112</b>(5):1448–1456. <h3>Disclosure of Interest</h3> None Declared
SP0177 Inhibitory Pathways of Synovial Angiogenesis
Authors: E. Brahn
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Introduction</h3> Angiogenesis occurs in a variety of normal processes, such as wound healing, organ development and the menstrual cycle. However, angiogenesis is also associated with numerous disease processes, including tumor growth, proliferative retinopathy, atherosclerosis and proliferative synovitis. Consequently, these pathologic processes are attractive therapeutic targets. Healthy joint vasculature is maintained by an appropriate balance between proangiogenic and antiangiogenic molecules. However, in rheumatoid arthritis (RA), this balance is disrupted; the levels of VEGF, hypoxia-inducible factor (HIF) and basic FGF (b-FGF), all of which are proangiogenic, are elevated in the joints of both patients with RA and in adjuvant-induced arthritis. The elevation of these proangiogenic factors occurs in the absence of adequate counterbalancing antiangiogenic factors. The new vasculature permits synovial hyperplasia which ultimately contributes to joint inflammation and structural damage. <h3>Results</h3> In the United States, there are already at least 13 FDA approved anti-cancer therapies with recognized antiangiogenic properties in oncology that target the endothelial cell, pericyte, or tumor cell. These agents, which interrupt critical cell signaling pathways involved in tumor angiogenesis and growth, comprise three primary categories: 1) Monoclonal antibodies directed against specific proangiogenic growth factors and/or their receptors; 2) Small molecule tyrosine kinase inhibitors (TKIs) of multiple proangiogenic growth factor receptors; and 3) Inhibitors of mTOR (mammalian target of rapamycin). In addition there are other angiogenic agents whose mechanisms are not completely understood. A variety of angiogenesis inhibitors are being examined for their potential in treating RA, and although none of these compounds have advanced beyond phase II clinical trials, several angiogenesis inhibitors have demonstrated efficacy in preclinical RA models. <h3>Conclusions</h3> Angiogenesis is an attractive therapeutic target although blood vessel growth is complex with multiple mechanisms. Different diseases may utilize different dominant pathways but surrogate markers such as bFGF, VEGF, and vessel density, may be helpful as predictors of likely candidates for therapeutic intervention. Angiogenesis inhibitors warrant further studies in rheumatic diseases. They lend themselves to combination therapies 1) that target multiple vessel proangiogenic pathways or 2) that could be used with biologic response modifiers. <h3>Disclosure of Interest</h3> None declared
Platelet and Fibrin Alterations on Thromboelastography in Children Undergoing Congenital Cardiac Surgery with Cardiopulmonary Bypass
Authors: Kim S. John, Elizabeth Villalobos-Menuey, Matthew Hathaway, Abimbola Onasoga, Jonathan Kaufman, Eduardo DaCruz, Jorge DiPaola, Marilyn J. Manco-Johnson
Journal: Blood (2014)
SAT0173 Lipoprotein(A) Concentrations in Rheumatoid Arthritis on Biologic Therapy: Results from The Cardiovascular in Rheumatology [CARMA] Study Project
Authors: M.C. García-Gόmez, M.A. Martín-Martínez, S. Castañeda, F. Sánchez-Alonso, M. Uriarte-Ecerrano, M.A. González-Gay, C. González-Juanatey, M. Romera-Baures, J. Santos-Rey, J.A. Pinto-Tasende, E. Quesada-Masachs, J. Tornero-Molina, O. Martinez-Gonzalez, T. Cobo-Ibáñez, E. Chamizo-Carmona, S. Manrique-Arija, D. Fábregas-Canales, F. Díaz-Gonzalez, J. Llorca
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Plasma concentrations of lipoprotein (a) [Lp(a)], a lipoprotein with proatherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as rheumatoid arthritis (RA) (1). There are few studies that evaluate the impact of biologic therapies on Lp(a) in RA (2), taking into account that with these new therapies a better control of inflammation is achieved. <h3>Objectives</h3> Evaluate the plasma concentrations of Lp(a) in Spanish RA patients on biologics therapy attending rheumatology outpatient clinics. <h3>Methods</h3> Baseline analysis of the CARMA project (CARdiovascular in rheuMAtology), a 10-year prospective study evaluating the risk of cardiovascular events in RA patients and other forms of inflammatory arthritis who attended rheumatology outpatient clinics at 67 hospitals in Spain. RA patients were classified into four categories: no biologic therapy, undergoing anti-TNF therapy, receiving anti-IL-6 receptor tocilizumab (TCZ), and other biologic therapies (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was biologic therapy. The model was adjusted for confounding factors. <h3>Results</h3> Seven hundred and seventy-five RA patients were analyzed. Total cholesterol and triglycerides concentrations were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index (TC/HDL-c) between TCZ-treated patients and patients without biological therapy was found. After adjusting for confounding factors, patients treated with biologic therapy had lower plasma concentrations of Lp(a) than those not undergoing biologic therapy. However, only TCZ-treated patients achieved statistically significant differences when compared with those not undergoing biologic therapy (β-coefficient: -0.303, 95% confidence interval: -0.558 to -0.047; p=0.02). <h3>Conclusions</h3> RA patients treated with tocilizumab, an inhibitor of interleukin 6 receptor, show lower plasma concentrations of Lp (a) compared to patients without biological therapy. <h3>References</h3> Garcia-Gomez C et al. J Rheumatol 2009, 36:1365–1370. McInnes IB et al. Ann Rheum Dis 2015, 74:694–702. <h3>Disclosure of Interest</h3> None declared
Computed Tomography (CT) Scan Response Stability and Gallium Scan Evaluation as On-Treatment Prognostic Parameters To Tailor Treatment Intensity of Newly Diagnosed Hodgkin’s Lymphoma (HL). A Prospective Phase II Study.
Authors: Alessandro Re, Samantha Ferrari, Paolo Frata, Claudio Pizzocaro, Fabio Franco, Valentina Rossi, AnnaMaria Pelizzari, Claudia Crippa, Nicoletta Petrella, Alessandra Tucci, Fabio Facchetti, Luigi Grazioli, Stefano Magrini, Giuseppe Rossi
Journal: Blood (2005)
Coincidence of JAK2V617F and BCR-ABL Is a Very Rare Event: Identification of 4 among 2317 Cases with Suspected CMPD.
Authors: Susanne Schnittger, Ulrike Bacher, Claudia Haferlach, Michael Flasshove, Erik Engel, Friedrich Ludwig, Judith Franz-Werner, Wolfgang Kern, Torsten Haferlach
Journal: Blood (2007)
Case 31-1984
Journal: New England Journal of Medicine (1984)

Presentation of Case A three-year-old boy was admitted to the hospital because of pancytopenia. He was well until two weeks earlier, when he became less active, with intermittent fever with a temperature as high as 38.9°C. Anorexia and vomiting developed. A physician made a tentative diagnosis of otitis media and prescribed amoxicillin, without improvement. Several days before admission the parents noticed periorbital petechiae. On the day of entry laboratory studies disclosed pancytopenia. The child was admitted to this hospital. There was a history of febrile seizures between the ages of 6 and 12 months, treated with phenobarbital. He had had . . .
Activity of ABT-737, an Inhibitor of BCL-2 Family Proteins, in Imatinib- or Dasatinib-Resistant CML Cells: Involvement of BCL-2 Family Proteins for Drug Resistance.
Authors: Tetsuzo Tauchi, Kousuke Nunoda, Tomoiku Takaku, Masahiko Sumi, Daigo Akahane, Goro Sashida, Junko H. Ohyashiki, Kazuma Ohyashiki
Journal: Blood (2005)
Immunohistologic Identification and Quantification of Human Bone Marrow Hematopoietic Stem Cells.
Authors: Federico Quaini, Mirca Lazzaretti, Lorena Carranza, Francesca Ferraro, Sabrina Bonomini, Konrad Urbanek, Cristina Mancini, Nicola Giuliani, Piero Anversa, Vittorio Rizzoli
Journal: Blood (2005)
Novel FAO Inhibitor Avocatin B Induces Apoptosis of Acute Monocytic Leukemia Cells in Adipocyte Co-Culture System Via ER Stress and ATF4 Activation
Authors: Yoko Tabe, Shinichi Yamamoto, Mika Kikkawa, Hikari Taka, Kaoru Mogushi, Hiromichi Mastushita, Takashi Miida, Michael Andreeff, Paul A Spagnuolo, Marina Konopleva
Journal: Blood (2015)
Temporal Changes in the Association Between Modifiable Risk Factors and Coronary Heart Disease Incidence
Authors: Ann Marie Navar, Eric D. Peterson, Daniel Wojdyla, Robert J. Sanchez, Allan D. Sniderman, Ralph B. D’Agostino, Michael J. Pencina
Journal: JAMA (2016)

This study uses data from 5 National Heart, Lung, and Blood Institute cohorts to investigate changes in association between modifiable risk factors and coronary heart disease from 1983-1995 and from 1996-2011.
PTH-019 Does Rectal Diclofenac Reduce Post ERCP Pancreatitis in The UK?
Authors: G Sheiybani, M Toolan, P Brydon, J Linehan, M Farrant, B Colleypriest
Journal: Gut (2016)

<h3>Introduction</h3> Post ERCP pancreatitis(PEP) occurs in up to 10% of unselected cases and carries significant morbidity. PEP is significantly higher in certain patient groups, for example females, young age, Sphincter of Oddi dysfunction, previous pancreatitis and following pancreatic duct cannulation. There is a growing body of evidence that NSAIDS should be used in PEP prophylaxis but use is still uncommon in the UK. The 2010 European Society for Gastrointestinal Endoscopy Guidelines on PEP recommends routine use of rectal NSAIDs in all patients. There is only one published RCT from the UK demonstrating the efficacy of NSAIDS in reducing PEP. Rectal diclofenac was introduced into ERCP practice at the RUH in two phases. Firstly, a selective use in patients determined to be at high risk as determined by criteria above. Secondly diclofenac was used routinely in all patients without contraindication. <h3>Methods</h3> A retrospective analysis of 5 years ERCP data was performed using readmission data, blood results, radiology reports and discharge summaries to identify patients with PEP from August 2010 – December 2015. The administration of rectal diclofenac post procedure was recorded from the endoscopy reporting system. Fisher’s exact test was used to statistically analyse categorical data. <h3>Results</h3> 1318 ERCPs were performed by 4 endoscopists during the study period with 66 (5.0%) cases of pancreatitis. 445 ERCPs were performed prior to the introduction of NSAID use during which time there were 35 (7.9%) episodes of PEP. During the selective period of NSAID use (only used if patient deemed high risk by endoscopist) 539 ERCPs were performed and 72 (13.4%) patients received NSAIDS. 17 (3.2%) developed PEP. 334 ERCPs were performed when NSAIDS were given to all patients without contraindication. 289 (86.5%) of patients received rectal diclofenac and 13 (3.9%) developed pancreatitis. There is a statistically significant decrease in PEP comparing the groups of patients receiving NSAIDS selectively (p = 0.0009) or routinely (p = 0.0172) when compared with none. There is no difference between the selective and routine group (p = 0.571). <h3>Conclusion</h3> The use of rectal diclofenac post ERCP decreases the rate of PEP when used in a selective or routine protocol. Despite a growing body of evidence for NSAIDS use routine administration is used by the minority of endoscopists in the UK. The evidence for use of NSAIDS in PEP is heterogeneous a number of factors including diagnostic criteria for pancreatitis, type and route of NSAID and selective high risk or routine use. We believe that this heterogeneity and lack of UK evidence accounts for the slow uptake of NSAIDS for PEP. Our data demonstrates that the introduction of a selective or routine use of NSAIDS for PEP in a DGH significantly decreases the risk of pancreatitis (RR 43.7%). <h3>Disclosure of Interest</h3> None Declared
SP0176 Role of Endothelial To Mesenchymal Transition in The Pathogenesis of The Vascular Alterations in Systemic Sclerosis
Authors: S.A. Jimenez
Journal: Annals of the Rheumatic Diseases (2016)

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe fibroproliferative microvascular alterations. Despite currently available therapeutic approaches SSc has a high mortality rate. The high mortality of SSc is largely caused by severe, progressive and generalized vascular involvement resulting in the development of multiple organ alterations including SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). These two complications have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process and the progressive fibroproliferative vasculopathy in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts originate from several sources including expansion of quiescent tissue fibroblasts and transmigration and tissue accumulation of circulating CD34+ bone-marrow-derived fibrocytes. Besides these sources, myofibroblasts may result from the phenotypic conversion of epithelial cells, adipocytes or endothelial cells into activated myofibroblasts. The transdifferentiation of endothelial cells into myofibroblasts involves numerous and complex biochemical, molecular, and gene expression events collectively known as endothelial to mesenchymal transition or EndoMT. Recently, it has been postulated that EndoMT may play a role in the development of tissue fibrosis and SSc-associated ILD and PAH. However, despite the demonstration of the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to the pathogenesis of tissue fibrosis and fibroproliferative vasculopathy in SSc has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of the vascular alterations in SSc and, more specifically, in the development of SSc-associated ILD and PAH will be critically reviewed. <h3>Disclosure of Interest</h3> None declared
Hematopoietic Repopulation, In Vivo, with Genetically Defined Clones Derived from HOXB4 Expressing ES-Cells.
Authors: Sandra Pilat, Sebastian Carotta, Bernhard Schiedlmeier, Kenji Kamino, Andreas Mairhofer, Manfred Schmidt, Christoph von Kalle, Peter Steinlein, Wolfram Ostertag, Christopher Baum, Hartmut Beug, Hannes Klump
Journal: Blood (2005)
BCR-ABL1-Positive Acute Lymphoblastic Leukemia Patients Treated with Only TKI Vs Conventional Chemo Plus TKI Therapy Show Similar DNA Alterations At Relapse Targeting Key Regulators of Tumor Suppression, Cell Cycle Control, and Lymphoid/B-Cell Development,
Authors: Ilaria Iacobucci, Heike Pfifer, Annalisa Lonetti, Cristina Papayannidis, Anna Ferrari, Stefania Trino, Maria Chiara Abbenante, Sarah Parisi, Simona Soverini, Antonella Vitale, Stefania Paolini, Emanuela Ottaviani, Carmen Baldazzi, Fabrizio Pane, Michele Baccarani, Oliver G. Ottmann, Giovanni Martinelli
Journal: Blood (2011)