tbuckley/cabot-search huggingface dataset:
THU0228 Efficacy Comparison with Tocilizumab, Interleukin-1 Inhibitors and Etanercept for Treatment of Systemic Juvenile Idiopathic Arthritis:
Authors: G. Horneff, A.C. Schultz, A. Hospach, G. Ganser, I. Foeldvari, A. Thon, R. Trauzeddel, F. Weller, K. Minden, J.P. Haas
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Since the approval of first biologics for JIA, such treatments in Germany are monitored prospectively by the BiKER registry. <h3>Methods</h3> sJIA pts documented in BIKER exposed to Etanercept (ETA), Tocilizumab (TOC) or IL-1inhibitors were identified. A 6-month therapy period was chosen as a meaningful time for early efficacy judgement. Intention to treat analysis (ITT) of JADAS10 was performed. Discontinuation due to inefficacy/intolerance was calculated as non-response. <h3>Results</h3> 205 sJIA patients (51% male) received 269 treatment courses with biologics (TOC 71, Anakina 36, Canakinumab 19, ETA 143). Median age and disease duration (ETA 3.3;TOC 3.3;IL-1i 3.0) were comparable. The choice of drug was influenced by the availability. ETA was started in 80% of pts before 2008 while in the TOC cohort all pts and in the IL-1i cohort 74% started therapy after 2008. Pre-treatment consisted of steroids in all pts, MTX in the ETA/TOC/IL-1i cohort in 88%/83%/76% and biologics preexposure was used in 2%/66%/86%. Concomitant treatment with systemic steroids was significantly less frequent with TOC (44%, p&lt;0,001) and IL-1i (44%, p&lt;0.001) compared to 83% with ETA. Concomitant MTX was used with ETA in 81% but significantly less frequent with TOC (64%; p=0.004) or IL-1i (44%; p&lt;0.0001). Also other DMARDs were used less frequently with TOC (9%) and IL-1i (4%) compared to ETA (24%). Systemic manifestations were present at baseline in: 8% ETA, 96% TOC and 38% IL-1i cohort. The mean±SD baseline JADAS was higher in the ETA cohort (20.7±9.1) than in the TOC cohort (16.2±10.6) or IL-1i cohort (7.8±8.9). At month 6, a marked decrease of the JADAS was noted in all cohorts. ITT analysis revealed a significant advantage of TOC and Il-1i over ETA (table). Significantly more pts reached a JADAS-Remission (JADAS≤1) upon TOC (OR/95CI 3.85/1.68–8.83/p&lt;0.001) or upon IL-1i (OR/95CI 4.55/1.92–10.77/p=0.003) than with ETA. Significantly more pts reached a JADAS-MDA (JADAS≤3.8) upon TOC (OR 3.55/1.49–8.46/p=0.003) or upon IL-1i (OR 4.5/1.87–10.84/p&lt;0.0001) than with ETA. ETA was more often discontinued due to inefficacy before month 6 than TOC or IL-1i. <h3>Conclusions</h3> A high proportion of pts showed a significant response to treatment especially with TOC or with IL-1i. After 6 months on treatment JADAS remission criteria were reached by up to 50% of patients while 60% to 65% reached JADAS minimal disease activity desoite much less steroids and DMARD used with TOC or IL-1i. ETA has been used in earlier times but it is less effective and it9s use in sJIA has markedly decreased in Germany. <h3>Disclosure of Interest</h3> None declared
In BCR-ABL1 Negative Myeloproliferative Neoplasms the Detection of JAK2exon12, MPLW515, CBL, KITD816V, FIP1L1-PDGFRA Mutations Are Closely Linked to Specific Entities, Whereas the JAK2V617F, TET2, or EZH2 Mutations Demonstrate a Broader Diversity: Patterns From Diagnostic Reports of 18,547 Patients Analyzed
Authors: Susanne Schnittger,, Christiane Eder, Frank Dicker, Vera Grossmann, Alexander Kohlmann, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach
Journal: Blood (2010)
The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks
Authors: Itamar D. Landau, Robert Egger, Vincent J. Dercksen, Marcel Oberlaender, Haim Sompolinsky
Journal: Neuron (2016)

Models of cortical dynamics often assume a homogeneous connectivity structure. However, we show that heterogeneous input connectivity can prevent the dynamic balance between excitation and inhibition, a hallmark of cortical dynamics, and yield unrealistically sparse and temporally regular firing. Anatomically based estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical simulations of this circuit indicate that the local network possesses substantial heterogeneity in input connectivity, sufficient to disrupt excitation-inhibition balance. We show that homeostatic plasticity in inhibitory synapses can align the functional connectivity to compensate for structural heterogeneity. Alternatively, spike-frequency adaptation can give rise to a novel state in which local firing rates adjust dynamically so that adaptation currents and synaptic inputs are balanced. This theory is supported by simulations of L4 barrel cortex during spontaneous and stimulus-evoked conditions. Our study shows how synaptic and cellular mechanisms yield fluctuation-driven dynamics despite structural heterogeneity in cortical circuits.
A Phase II Study of Myeloablative I-131-Anti CD-20 (Tositumomab) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Adults ≥60 Years of Age with High-Risk Relapsed or Refractory B-Cell Lymphoma.
Authors: Ajay K. Gopal, Joseph G. Rajendran, Ted A. Gooley, John M. Pagel, Darrell R. Fisher, Stephen Petersdorf, David G. Maloney, Frederick R. Appelbaum, Oliver W. Press
Journal: Blood (2005)
Mutational analysis of EGFR, c-KIT, PDGFRs, BRAF and KRAS, and expression of ALK and PD-L1 in a series of 103 thymic epithelial tumors with different histology
Authors: L. Longo, F. Barbieri, F. Bertolini, M. Tiseo, M. Migaldi, D. Giardina, G. Montanari, G. Vincenzi, C. Tomasello, S. Noventa, A. Spallanzani, P. Sighinolfi, G. Sartori, P. Bordi, G. Rossi
Journal: Annals of Oncology (2015)
VPREB1 Deletions Occur Independent of Lambda-Light Chain Rearrangement and Predict Worse Outcome In Pediatric Acute Lymphoblastic Leukemia (ALL)
Authors: Rodney R. Miles, Jonathan Downie, Mona S. Jahromi, Deepa Joshi, Vladimir Rodic, Markus Muschen, Jun J. Yang, William E. Evans, Nathan Meeker, Nikolaus Trede, J. Kimble Frazer, Phillip Barnette, Joshua D. Schiffman
Journal: Blood (2010)
Thresholds for Abdominal Aortic Aneurysm Repair in England and the United States
Authors: Alan Karthikesalingam, Alberto Vidal-Diez, Peter J. Holt, Ian M. Loftus, Marc L. Schermerhorn, Peter A. Soden, Bruce E. Landon, Matthew M. Thompson
Journal: New England Journal of Medicine (2016)

Thresholds for repair of abdominal aortic aneurysms vary considerably among countries.We examined differences between England and the United States in the frequency of aneurysm repair, the mean aneurysm diameter at the time of the procedure, and rates of aneurysm rupture and aneurysm-related death. Data on the frequency of repair of intact (nonruptured) abdominal aortic aneurysms, in-hospital mortality among patients who had undergone aneurysm repair, and rates of aneurysm rupture during the period from 2005 through 2012 were extracted from the Hospital Episode Statistics database in England and the U.S. Nationwide Inpatient Sample. Data on the aneurysm diameter at the time of repair were extracted from the U.K. National Vascular Registry (2014 data) and from the U.S. National Surgical Quality Improvement Program (2013 data). Aneurysm-related mortality during the period from 2005 through 2012 was determined from data obtained from the Centers for Disease Control and Prevention and the U.K. Office of National Statistics. Data were adjusted with the use of direct standardization or conditional logistic regression for differences between England and the United States with respect to population age and sex.During the period from 2005 through 2012, a total of 29,300 patients in England and 278,921 patients in the United States underwent repair of intact abdominal aortic aneurysms. Aneurysm repair was less common in England than in the United States (odds ratio, 0.49; 95% confidence interval [CI], 0.48 to 0.49; P<0.001), and aneurysm-related death was more common in England than in the United States (odds ratio, 3.60; 95% CI, 3.55 to 3.64; P<0.001). Hospitalization due to an aneurysm rupture occurred more frequently in England than in the United States (odds ratio, 2.23; 95% CI, 2.19 to 2.27; P<0.001), and the mean aneurysm diameter at the time of repair was larger in England (63.7 mm vs. 58.3 mm, P<0.001).We found a lower rate of repair of abdominal aortic aneurysms and a larger mean aneurysm diameter at the time of repair in England than in the United States and lower rates of aneurysm rupture and aneurysm-related death in the United States than in England. (Funded by the Circulation Foundation and others.).
Phase 2 Trial of Entospletinib (GS-9973), a Selective Syk Inhibitor, in Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
Authors: Jeff P. Sharman, Leonard M. Klein, Michael Boxer, Kathryn S. Kolibaba, Steve Abella, Julie Di Paolo, Clarence Eng, Jing Hu, Jing He, Anita Reddy, Christopher A. Yasenchak
Journal: Blood (2015)
A Phase I/II Study of Bortezomib in Combination with Melphalan and Prednisolone in Japanese Patients with Newly Diagnosed Multiple Myeloma
Authors: Kenshi Suzuki, Kiyoshi Ando, Akira Sakai, Shinsuke Iida, Michinori Ogura, Kensei Tobinai, Morio Matsumoto, Kosei Matsue, Yasuhito Terui, Kazuteru Ohashi, Takaaki Chou, Kazutaka Sunami, Atsushi Shinagawa, Nobuyuki Aotsuka, Hirohiko Shibayama, Takayuki Takahashi, Harumi Yamamoto Mukai, Tomomitsu Hotta
Journal: Blood (2011)
Interferon-Alpha Preferentially Targets JAK2V617F-Positive Rather Than Wild-Type Early Progenitor Cells in Myeloproliferative Disorders.
Authors: Florence Pasquier, Carole Tonetti, Rodolphe Besancenot, Bruno Cassinat, Jean-Jacques Kiladjian, Olivier Herault, Philippe Rameau, Catherine Lacout, Jean-Luc Villeval, William Vainchenker, Ronan Chaligné, Stephane Giraudier
Journal: Blood (2009)
AB0287 Psychiatric Disorders in RA Patients: Relation with Fatigue, Sleep Quality and Quality of Life
Authors: D. Durmus, G. Sarisoy, C. Aslan, Y. Doydu, G. Alayli, E. Unverdi, A. Bilgici, O. Kuru
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease that predominantly affects the synovial joints and the periarticular structures, leading to persistent pain, functional deterioration, disability, sleep disturbance, and lower quality of life. Psychiatric disturbances are frequently observed in these patients. <h3>Objectives</h3> The aim of this trial was to investigate I) the psychiatric disorders in RA and II) the effect of concurrent psychiatric disorders on pain, fatigue, disease activity, sleep quality and health-related quality of life (HRQOL). <h3>Methods</h3> The patients who fulfilled the American College of Rheumatology (ACR) criteria for RA were recruited. All the patients were interviewed by a psychiatrist. The psychiatric disorders were evaluated with the Turkish Structured Clinical Interview for DSM-VI Axis I Disorders (SCID-I). Sociodemographic data, disease activity (DAS 28 score) and disease duration were reported. Pain was evaluated with visual analogue scale (VAS), fatigue with Multidimensional Assessment of Fatigue (MAF), and quality of life with 36-item Short Form Health Survey (SF-36), and sleep quality with Pittsburgh Sleep Quality Index (PSQI). <h3>Results</h3> One hundred patients with RA were studied (90% women, mean age 52.02±12.74 years; disease duration 10.29±8.99 years). Forty-six (46.0%) patients were diagnosed with a psychiatric disorder. Adjustment disorder (n=15) and major depressive disorder (n=12) were frequently observed in these patients. When we divided the groups as the RA patients with psychiatric disorders and the RA patients without psychiatric disorders, RA patients with psychiatric disorders had significantly higher pain scores (p=0.035) and fatigue scores (p=0.005). There was no difference between groups regarding disease activity. The scores of all domains of the SF-36 were significantly lower in RA patients with psychiatric disorders (p&lt;0.05 for all). While there was no significant difference between groups regarding sleep duration, usual sleep efficiency and sleeping aid use, significant differences in sleep quality, sleep latency, sleep disturbance, daytime sleepiness and PSQI total score were observed. These scores were higher in RA patients with psychiatric disorders (p&lt;0.05). <h3>Conclusions</h3> The rate of psychiatric disorders in RA patients was found to be 46% in the present study. We also determined that concomitant psychiatric disorders in RA patients were associated with significantly lower sleep quality and HRQOL and higher fatigue. Early identification of psychiatric disorders in RA patients and early referral to a multidisciplinary psychiatric team are necessary to improve the quality of life, sleep quality, and to reduce fatigue. <h3>Disclosure of Interest</h3> None declared
“Clinical and Molecular Heterogeneity of Eosinophilia-Associated Myeloproliferative Neoplasms with a Translocation t(5;12)”.
Authors: Darko Gosenca, Philipp Erben, Claudia Haferlach, Rainer Schwerdtfeger, Herrad Baurmann, Georg Bolz, Juliana Popa, Torsten Haferlach, Wolf-Karsten Hofmann, Andreas Hochhaus, Andreas Reiter
Journal: Blood (2009)
Novel VWF Sequence Variations Identified in a Second Cohort of Index Cases Enrolled in the TS Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCB-VWD).
Authors: Daniel B. Bellissimo, Pamela A. Christopherson, Sandra L. Haberichter, Veronica H. Flood, Joan Cox Gill, Kenneth D. Friedman, Robert R. Montgomery, The Zimmerman Project Investigators
Journal: Blood (2008)
AB0691 Oblique Views Have Advantages over Antero-Posterior View Radiographs in Assessing Sacroiliitis: An Imaging Study
Authors: Z. Hu, P. Zhang, J. Qi, M. Qiu, X. Guo, J. Gu
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Radiograph of antero-posterior (A-P) view of pelvis is usually used to diagnose sacroiliitis. Magnetic resonance imaging (MRI) can detect lesions early in the disease course before they can be seen on radiography. The severity of sacroiliitis may be different as detected by MRI or by A-P view X-ray. The oblique view of pelvis may provide additional information that makes it closer to the finding of MRI than A-P view X-ray. <h3>Objectives</h3> To record lesions of sacroiliac joint (SIJ) seen on A-P view and oblique views radiographs and MRI in patients with axial Spondyloarthritis (SpA), and to analyze whether oblique views have advantages over A-P view radiographs in assessing sacroiliitis. <h3>Methods</h3> Three readers blinded graded the sacroiliitis according to the modified New York criteria seen on A-P view, oblique views and MRI from 182 patients with axial SpA. We summarized the characteristics of scores assessed by three kinds of imaging methods and calculated the sensitivity, specificity, positive and negative likelihood ratio of A-P view and oblique views radiographs for diagnosing axial SpA with MRI as the gold-standard. <h3>Results</h3> The total accuracy of oblique views was higher than that of A-P view in assessing sacroiliitis as referred to the data of MRI (82.8% vs. 71.6%, p&lt;0.01). The agreements were higher between oblique views and MRI than that between A-P view and MRI in the SIJs graded ≤2, especially in patients with symptom duration less than 2 years (all p&lt;0.01). But in the SIJs graded &gt;2 and in patients with symptom duration more than 2 years, there were no differences using A-P view or oblique views to assess sacroiliitis (all p&gt;0.05). Oblique views had high sensitivity, while A-P view had moderate sensitivity for diagnosing axial SpA in the SIJs graded ≤2. <h3>Conclusions</h3> We recorded and analyzed the sacroiliitis assessed by A-P view, oblique views radiographs and MRI and found that oblique views had some advantages over A-P view radiographs in assessing sacroiliitis. <h3>References</h3> van Gaalen FA, Bakker PA, de Hooge M, et al. Assessment of sacroiliitis by radiographs and MRI: where are we now? Curr Opin Rheumatol 2014;26:384–8. van Tubergen A, Weber U. Diagnosis and classification in spondyloarthritis: identifying a chameleon. Nat Rev Rheumatol 2012;8:253–61. Eshed I, Hermann KG. Novel imaging modalities in spondyloarthritis. Curr Opin Rheumatol 2015;27:333–42. <h3>Disclosure of Interest</h3> None declared
Prognostic Impact of Tumor Infiltrating FOXP3 Positive Regulatory T Cells in Diffuse Large B-Cell Lymphoma at Diagnosis.
Authors: Jae-Yong Kwak, Na-Ri Lee, Eun-Kee Song, Kyu Yun Jang, Ha Na Choi, Woo Sung Moon, KeunSang Kwon, Ju-Hyung Lee, Chang-Yeol Yim
Journal: Blood (2007)
Decitabine Induced the Cell Differentiation, Decreased Malignant Potential, and Increased Susceptibility to Apoptosis Via a Death Receptor Pathway with Hypomethylation of MS4A3, PAR-4, APITD1, LOX in Myelodysplastic Syndrome Cell Line, MDS-L
Authors: Rie Nishi, Takahiro Yamauchi, Miyuki Ookura, Yasufumi Matsuda, Toshiki Tasaki, Kaoru Tohyama, Takanori Ueda
Journal: Blood (2014)
AB0663 Efficacy and Safety of Adalimumab in Patients with Axial Spondyloarthritis - An Investigator-Initiated Randomized Placebo-Controlled Trial: Table 1
Authors: S. Krabbe, M. Østergaard, I.J. Sørensen, B. Jensen, O.R. Madsen, G.P. Eng, K.H. Asmussen, J. Møller, L. Balding, S.J. Pedersen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> This study investigates the effect of adalimumab (ADA) in patients with axial spondyloarthritis (axSpA). <h3>Objectives</h3> In an investigator-initiated randomized, placebo-controlled, double-blinded trial (NCT01029847) the efficacy of adalimumab was investigated in patients with axSpA according to the Assessment of Spondyloarthritis International Society (ASAS) criteria.(1,2) <h3>Methods</h3> 49 patients with axSpA, BASDAI≥4.0 despite treatment with NSAID and clinical indication for TNFα inhibitor treatment were randomized to s.c. placebo (PLA) or ADA 40 mg eow from baseline to week 6. All patients received ADA from weeks 6 to 24. At week 24, patients with a BASDAI reduction &gt;50% or 2.0 were considered responders. MRI of the spine was scored according to SPARCC Spine Inflammation Index by an experienced reader blinded to all other data. Data from the randomized period (week 0–6) were analysed by Chi-square, unpaired t-tests and Mann-Whitney U tests as appropriate. <h3>Results</h3> Mean (range) age was 38 years (20–61), symptom duration 12 years (0–45) and time since diagnosis 3 years (0–38). 51% were males, 74% HLA-B27 positive, 20% had a history of uveitis, 4% of psoriasis and 6% of inflammatory bowel disease. At week 24, a BASDAI reduction &gt;50% or 2.0 was attained by 32 of 49 (65%) patients (58% and 72% in the PLA and ADA groups, respectively). 61% of patients achieved ASAS 20 response and 61% ASAS 40 response. From baseline to week 6, the SPARCC MRI spine score improved significantly more in the ADA group than in the PLA group, as did clinical variables (Table): Treatment was discontinued in 5 patients due to adverse events during ADA treatment, due to rash (1), unspecified allergic reaction (1), paresthesia and reduced sensibility of 2 fingers (1), back pain worsening (1), and hospitalization due to myalgia and malaise (1). <h3>Conclusions</h3> Adalimumab significantly improved clinical and MRI measures of disease activity already at week 6 compared to placebo. 2/3 of patients achieved the clinical endpoint at week 24, confirming the clinical efficacy in axSpA. <h3>References</h3> Maxwell et al. Cochrane Database Syst Rev. 2015;4:CD005468. Rudwaleit et al. Ann Rheum Dis 2009;68:777–83 <h3>Disclosure of Interest</h3> None declared
Abstract 2343: Tumor microenvironment regulates the fate of myeloid cells by controlling STAT3 activity
Authors: Vinit Kumar, Pingyan Cheng, Thomas Condamine, Dmitry Gabrilovich
Journal: Cancer Research (2015)

Abstract The abnormal differentiation of myeloid cells is one of the key features of altered immune response in cancer. Myeloid derived suppressor cells (MDSC) are a major component of immune suppressive network. MDSC accumulate in large numbers in peripheral lymphoid organs and inside tumors. Previous data indicated that the fate of MDSC depends on the localization of these cells. In contrast to peripheral lymphoid organs such as spleen, inside tumors, MDSC rapidly differentiate to tumor associated macrophages with potent immune suppressive activity. We have demonstrated that this phenomenon is mediated by dramatic down-regulation of STAT3 activity in MDSC at tumor site. In cancer patients, MDSC at tumor site also had substantially lower level of pSTAT3 than MDSC in peripheral blood. These results were unexpected, since high level of STAT3 activity is a hallmark of MDSC present in blood and lymphoid organs. The mice with constitutively active STAT3 had shown the dramatic expansion of MDSC and down-regulation of macrophage population in tumor microenvironment, emphasizing the crucial role of STAT3 in myeloid cell differentiation. Hypoxia is an intricate part of tumor microenvironment. We have found that hypoxia caused the down-regulation of STAT3 activity in MDSC. However, the effect of hypoxia on STAT3 activity was not observed in tumor cells. We further demonstrate that the up-regulation of CD45 tyrosine phosphatase activity in MDSC exposed to hypoxia in tumor site was responsible for down-regulation of STAT3 activity. Using KO model we have shown that MDSC devoid of CD45 failed to experience the effect of hypoxia on pSTAT3 down-regulation as well as their differentiation to macrophage at tumor site. Furthermore, the positive regulation of CD45 activity in hypoxia was mediated by the disruption of CD45 protein dimerization via sialylation. The treatment of sialidase abrogated the effect of hypoxia on STAT3 activity in MDSC and differentiation of MDSC to macrophages. This novel mechanism of regulation of myeloid cell differentiation by STAT3 may provide rationale for re-evaluation of therapeutic strategies in cancer. Citation Format: Vinit Kumar, Pingyan Cheng, Thomas Condamine, Dmitry Gabrilovich. Tumor microenvironment regulates the fate of myeloid cells by controlling STAT3 activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2343. doi:10.1158/1538-7445.AM2015-2343