tbuckley/cabot-search huggingface dataset:
THU0245 Individual versus Combined BLYs Or/and april Neutralization Reveals Developmental Plasticity for Plasma Cell Survival Factor Requirements
Authors: P. Haselmayer, M. Vigolo, J. Nys, P. Schneider, H. Hess
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The role of the TNF family cytokine APRIL (a proliferation inducing ligand) in the etiology and pathogenesis of autoimmunity is incompletely understood. The inhibition of B cell survival factors in the NZBWF1 mouse model of systemic lupus erythematosus (SLE) thus far revealed similar efficacy profiles for compounds that neutralize BLyS (B lymphocyte stimulator, also known as BAFF) only, or both BLyS and APRIL (1, 2). Strategies that exclusively target APRIL are sparse, mostly confined to genetic approaches and do not dissect its temporal requirements in disease progression. <h3>Objectives</h3> Comparison of single versus dual pharmacological inhibition of BLyS and APRIL in a mouse model for the human autoimmune disease SLE. <h3>Methods</h3> Reagents that neutralize either APRIL alone (an anti-APRIL antibody), BLyS alone (BAFFR-Fc), or both BLyS and APRIL (TACI-Fc), were administered to NZBWF1 mice after the onset of autoimmunity, but before nephritis occurred. <h3>Results</h3> The inhibition of APRIL alone was inefficient, in contrast to BLyS single antagonism, which instead delayed lupus symptoms, or to the dual inhibition of BLyS and APRIL, which arrested further disease development, autoantibody production, immune complex deposition in glomeruli and prevented onset of nephritis. While studying the plasma cell compartment over time in a T-dependent hapten/carrier immunization system, developmental plasticity in terms of survival factor requirements was observed. Moreover, a maturation window for plasma cells was identified during which APRIL predominantly mediated survival. The results indicate that plasma cells are flexible in the use of APRIL or BLyS to support their survival in the bone marrow niche. <h3>Conclusions</h3> These results suggest that targeting plasma cells by neutralization of both BLyS and APRIL might be beneficial to prevent autoantibody-mediated damages in SLE. <h3>References</h3> Ramanujam M, et al. J Clin Invest 116: 724–734; Ramanujam M, et al. Arthritis Rheum 62: 1457–1468. <h3>Disclosure of Interest</h3> P. Haselmayer Employee of: Merck KGgA, M. Vigolo: None declared, J. Nys Shareholder of: AstraZeneca, Employee of: Medimmune, P. Schneider Grant/research support from: EMD Serono, a subsidiary of Merck, KGaA, H. Hess Shareholder of: Merck KGaA, Employee of: Merck KGaA
AB0798 Can Anti-Osteoporotic Therapy Reduce Adjacent Fracture in Magnetic Resonance Imaging-Proven Acute Osteoporotic Vertebral Fractures?: Table 1.
Authors: Y.-C. Chen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Adjacent fracture of the cemented vertebrae may result from unfilled space left during the procedure or from crushed fragile trabeculae underneath the cement during follow-up, suggesting impaired bone marrow integrity of the injured vertebrae. Anti-osteoporotic therapy is reported to increase spinal, total hip, and femoral neck bone mineral density<sup>1</sup>. If treating osteoporosis does have a positive impact on adjacent fracture among patients who have undergone vertebroplasty, there will be several important potential implications for managing skeletal health specifically and for the health care of the elderly in general. <h3>Objectives</h3> This study aimed to determine if anti-osteoporotic therapy can decrease the risk of adjacent fracture in patients with acute vertebral fracture after vertebroplasty. <h3>Methods</h3> This retrospective study reviewed of cases of osteoporosis patients with magnetic resonance imaging (MRI)-proven acute vertebral fractures between 2001 and 2007. Osteoporotic patients were investigated as determined by pre-operative MRI with subsequent adjacent fracture of the cemented vertebrae and for the possibility of anti-osteoporotic therapy decreasing the progression of collapse after a minimum of 6 months follow-up. All associated co-morbidities were recorded, as well as the use of anti-osteoporotic drugs (i.e., alendronate, raloxifen, calcitonin, and teriparatide). Cox regression analysis was also performed. <h3>Results</h3> The 192 patients with acute vertebral fractures who underwent vertebroplasty and anti-osteoporotic therapy had a mean age of 74.40±6.41. The basic characteristics of patients with and without adjacent fracture differed in age, body mass index, rheumatoid arthritis, and use of glucocorticoids and anti-osteoporotic drugs (Table 1). Using the Kaplan-Meier curve, anti-osteoporotic therapy after vertebroplasty had a significant effect on adjacent fracture (<i>p</i>=0.037, by log rank text). After adjusting for potential confounders, patients with anti-osteoporotic therapy still had a lower adjacent fracture rate than patients without anti-osteoporotic therapy (<i>p</i>=0.006; HR: 2.137, 95% CI: 1.1238–3.690). The adjacent fracture rate also increased in old age (<i>p</i>=0.019; HR: 1.049; 95% CI:1.008–1.039) and among smokers (<i>p</i>=0.026; HR: 3.891; 95% CI: 1.175–12.890). <h3>Conclusions</h3> In this study, adjacent fracture of cemented vertebrae is inevitable after vertebroplasty but can be mitigated by anti-osteoporotic therapy to increase bone mass. <h3>References</h3> Center JR, et al. J Clin Endocrinol Metab. 2011;96(4):1006–14. <h3>Disclosure of Interest</h3> None declared
FRI0312 Predictors of Incident Episodes of Proteinuria among Patients with Systemic Lupus Erythematosus
Authors: L.S. Magder, A. Duarte-Garcia, E. Barr, M. Petri
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Lupus nephritis remains one of the most devastating SLE complications, occurring in over 50% of the patients. It is important to identify clinical conditions that precede nephritis for the purposes of patient care and to identify preventive strategies. Most previous studies of predictors of incident nephritis in SLE are cross-sectional or do not incorporate time-varying predictors. <h3>Objectives</h3> We leveraged a large clinical cohort which evaluated patients quarterly to identify fixed and time-varying predictors of lupus nephritis. <h3>Methods</h3> Since 2006, the urine protein/creatinine ratio was measured quarterly in patients in our SLE cohort. This analysis was based on cohort follow-up after 2006 in patients who did not have a history of diabetes and who did not have a prior episode of sustained elevated proteinuria, nor a history of nephritis, renal insufficiency, or failure. Among these patients, we defined an incident case of proteinuria as two or more measures of urine protein/creatinine (or 24-hour protein measure) greater than 0.5 in two visits separated by more than 30 days and less than 180 days, among patients with no prior episodes of proteinuria. We estimated rates of incident proteinuria in subgroups of patients defined by time-invariant and time-varying predictors. <h3>Results</h3> Among 895 patients included in the analysis, 840 (94%) were female, and 518 (58%) were Caucasian, 304 (34%) African-American, with mean age of 42 at the start of follow-up. We observed 58 incident cases of proteinura over a span of 4669 person-years of cohort follow-up. The overall rate of incident proteinuria was 12.4 per 1000 person-years. The Table shows the association between select predictors and the rate incident proteinuria. The rate was significantly lower among those of older age, and significantly higher among those who were not Caucasian. Among those with a history of low C3, the rate was 8 times higher, and highest among those with a recent measure of low C3. The rate among those prescribed hydroxychloroquine was similar to those not prescribed hydroxychloroquine. Among those taking medicine for hypertension, the rate among those prescribed ACE inhibitor or ARB was similar to the rate among those prescribed other treatments. <h3>Conclusions</h3> Older SLE patients who have not previously had renal involvement are at low risk for developing proteinuria. The highest rates of incident proteinuria were among those with recent low complement. There was not strong evidence that hydroxychloroquine or ACE inhibitor9s reduced the risk of proteinuria. <h3>Disclosure of Interest</h3> None declared
Lenalidomide Decreases PD-1 Expression, Depletes Regulatory T-Cells and Improves Cellular Response to a Multiple Myeloma/Dendritic Cell Fusion Vaccine In Vitro
Authors: Katarina Luptakova, Brett Glotzbecker, Heidi Mills, Dina Stroopinsky, Baldev Vasir, Jacalyn Rosenblatt, Donald Kufe, David Avigan
Journal: Blood (2010)
Presence of Prior-to-Treatment BCR-ABL Mutations In CD34+CD38- Stem Cells of Newly Diagnosed Chronic Phase CML Patients and Their Correlation with Imatinib Resistance: Implications of Cancer Pharmacogenomics and Pre-Therapeutic Genetic Testing In Personalized Treatment of BCR-ABL+ Leukemia
Authors: Zafar Iqbal, Mudassar Iqbal, Tanveer Akhtar, Mubashar Iqbal Naqvi, Ammara H Tahir, Tariq Jameel Gill, Muhammad Naeem Abbas, Abid Jamil, Abid Sohail Taj, Dr Abd-Al-Qayyum, Najeeb ur-Rehman, Muhammad Ferhan, Ijaz Hussain Shah, Muhammad Khalid, Weng Xian Qin, Ahmad Mukhtar Khalid, Mahwish Khan, Aamer Aleem, Shahid Mahmood Baig
Journal: Blood (2010)
SNP-A Karyotyping Demonstrates a High Incidence of Segmental Uniparental Disomy in Patients with CMML and Shows Impact of Newly Identified Chromosomal Aberrations on Clinical Course.
Authors: Andrew J. Dunbar, Lukasz P. Gondek, Ramon V. Tiu, Judith E. Karp, Xiao Fei P. Wang, Mark J. Levis, Michael A. McDevitt, Jaroslaw P. Maciejewski
Journal: Blood (2007)
Bone Marrow Transplantation from Alternative Donors in Children Receiving Rabbit ATG for Prophylaxis of Graft-Versus-Host Disease.
Authors: Asahito Hama, Hiroshi Yagasaki, Nobuhiro Nishio, Nao Yoshida, Makito Tanaka, Hirokazu Hidaka, Yoshiyuki Takahashi, Kimikazu Matsumoto, Koji Kato, Seiji Kojima
Journal: Blood (2006)
Idelalisib Treatment Is Associated with Improved Cytopenias in Patients with Relapsed/Refractory iNHL and CLL
Authors: Susan O'Brien, Andrew John Davies, Ian W. Flinn, Ajay K Gopal, Thomas J. Kipps, Gilles A. Salles, Terry Newcomb, Christopher C. Waldapfel, Zhihai Zhang, Stephan Stilgenbauer
Journal: Blood (2015)
FRI0506 Pregnancy in Patients with Undifferentiated Connective Tissue Disease: Clinical Outcomes in 78 Cases
Authors: R. Vagelli, C. Tani, L. Carli, D. Totti, M. Tristano, F. Strigini, M. Mosca
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Pregnancy is considered to be an important factor that may affect the course of autoimmune diseases; few data are currently available in the literature on pregnant patients with diagnosis of undifferentiated connective tissue disease (UCTD). <h3>Objectives</h3> To assess the outcome of pregnancy and evaluate the percentage of disease flare in a cohort of patients with UCTD. <h3>Methods</h3> We conducted a prospective study on 78 pregnancies in 64 UCTD patients, regularly monitored from the positive pregnancy test until the postpartum period by a multidisciplinary team including rheumatologists and obstetricians at our unit from 2000 to 2015. <h3>Results</h3> The mean age of patients at pregnancy was 34.1 (range 21–43) and the mean disease duration was 7.26 years. Only 3 patients presented hematologic disease activity at the beginning of pregnancy and none of the patients had experienced previous renal involvement. 20.8% of UCTD patients presented antiphospholipid (aPL)-antibodies positivity (only 2 cases of triple positivity of LAC, anti-β2GPI and ACLA) and the same percentage had anti-Ro positivity. At the beginning of pregnancy 38.5% of patients was taking treatment: 20 hydroxychloroquine, 13 low doses of steroids and 11 aspirin. On average, the duration of pregnancy was 39 weeks (range 34–42), the mean birth weight was 3118.3 g (range 2122–4500 g). Eight pregnancies (10.5%) ended in miscarriage in the first trimester; the following obstetric complications occurred in 34.7% of the remaining successful deliveries: preterm delivery, small or large for gestational age (SGA/LGA), preeclampsia, premature membrane ruptures (PROM), increased transaminases. Six patients experienced a disease flare, 3 during pregnancy and 3 in puerperium: of these patients, 3 had a major flare progressing to SLE with the occurrence of lupus nephritis. No correlations were found between the incidence of obstetric complications and the positivity of aPL-antibodies, the use of steroids, the alterations of uterine artery Doppler velocimetry. The only variable correlated with the incidence of flare was the positivity of anti ds-DNA at the beginning of the pregnancy (p&lt;0.001). <h3>Conclusions</h3> Our data suggest that UCTD as other connective tissue diseases should be carefully monitored during pregnancy as these patients present with obstetric complications. As in non pregnant UCTD patients anti-dsDNA are predictors of possible evolution to SLE, therefore these patients need careful monitoring during pregnancy. <h3>Disclosure of Interest</h3> None declared
Chronic Imatinib Mesylate Exposure Leads to Reduced Intracellular Drug Accumulation in K562 Cells Measured by High-Performance Liquid Chromatography.
Authors: Yongqian Jia, Zhen Yan, Huanling Zhu, Ting Niu, Tingting Zeng, Feng Nan, Mengzhi Liang
Journal: Blood (2005)
Mutational Landscape of Patients with Myelofibrosis That Do Not Harbor Mutations in JAK2, MPL and Calreticulin Driver Genes
Authors: Giada Rotunno, Paola Guglielmelli, Annalisa Pacilli, Tiziana Fanelli, Carmela Mannarelli, Alessandro Pancrazzi, Alessandro M. Vannucchi
Journal: Blood (2015)
Cytoplasmic Cyclin E Predicts Recurrence in Patients with Breast Cancer
Authors: Kelly K. Hunt, Cansu Karakas, Min Jin Ha, Anna Biernacka, Min Yi, Aysegul A. Sahin, Opoku Adjapong, Gabriel N. Hortobagyi, Melissa L. Bondy, Patricia A. Thompson, Kwok Leung Cheung, Ian O. Ellis, Sarah Bacus, W. Fraser Symmans, Kim-Anh Do, Khandan Keyomarsi
Journal: Clinical Cancer Research (2016)

Purpose: Low molecular weight cyclin E (LMW-E) detected by Western blot analysis predicts for reduced breast cancer survival; however, it is impractical for clinical use. LMW-E lacks a nuclear localization signal that leads to accumulation in the cytoplasm that can be detected by IHC. We tested the hypothesis that cytoplasmic staining of cyclin E can be used as a predictor of poor outcome in different subtypes of breast cancer using patient cohorts with distinct clinical and pathologic features.Experimental Design: We evaluated the subcellular localization of cyclin E in breast cancer specimens from 2,494 patients from 4 different cohorts: 303 from a prospective study and 2,191 from retrospective cohorts [NCI, MD Anderson Cancer Center (MDA), and the United Kingdom (UK)]. Median follow-up times were 8.0, 10.1, 13.5, and 5.7 years, respectively.Results: Subcellular localization of cyclin E on IHC was associated with full-length (nuclear) and low molecular weight isoforms (cytoplasmic) of cyclin E on Western blot analysis. In multivariable analysis, cytoplasmic cyclin E staining was associated with the greatest risk of recurrence compared with other prognostic factors across all subtypes in three (NCI, MDA, and UK) of the cohorts. In the MDA cohort, cytoplasmic cyclin E staining outperformed Ki67 and all other variables as prognostic factors.Conclusions: Cytoplasmic cyclin E identifies patients with the highest likelihood of recurrence consistently across different patient cohorts and subtypes. These patients may benefit from alternative therapies targeting the oncogenic isoforms of cyclin E. Clin Cancer Res; 23(12); 2991-3002. ©2016 AACR.
SAT0495 Chikungunya Viral Arthritis in Mexico: Inflammatory Biomarkers, Disability and Disease Activity Index May Be Predictors of Chronic Arthritis
Authors: J. Sepúlveda-Delgado, O.L. Vera-Lastra, L.J. Jara, K.D.C. Trujillo Murillo, R.A. Sanchez Gonzalez, A. Lugo Trampe, A. Contreras Contreras, A. Mendoza Torres, J.C. Ramirez Valdespino, M. Ocaña Sibilla
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Between 2013 to 2014 autochthonous cases ChikV virus were confirmed in the Americas and Mexico. The clinical and inflammatory profile and the prevalence of chronic disease were analyzed in Mexican patients. <h3>Objectives</h3> To describe clinical profile, self reported-disability, inflammatory biomarkers and chronic articular (CA) disease during 10 month follow-up in ChikV Mexican patients. <h3>Methods</h3> Ten patients with ChikV confirmed by real-time PCR were included. Clinical manifestations, Disease Activity Index (DAS-28), self-reported disability by 32 item WHODAS-2 score and inflammatory biomarkers (C-reactive protein (CRP), eritrosedimentation rate (ESR), Rheumatoid Factor (RF), high sensivity Interleukin-6 (hsIL-6) were measured at onset and every month until 10 months of follow-up. <h3>Results</h3> Ten patients (6 women and 4 men) with mean age 48.0 15.04 years-old were followed. Acute symptoms were: fever (100%), arthralgias (100%), myalgias (80%), rash (80%), synovitis (60%), nausea (50%), vomiting (20%) and back pain (20%); number of tender joints was 13.8 (SD 5.09) and number of articulations with synovitis was 7.1 (SD 3.78). At diagnosis biomarkers were: CRP 5.09 (SD 7.23) mg/dl, ESR: 32.6 (SD 17.5) mm/h, rF: 64 (SD 21.7) IU/ml and hsIL-6: 17 (SD 10.3) pg/ml. At diagnosis WHODAS-2 score was 74.5 (SD 7.59) % and DAS-28 was 4.37 (SD 0.78). Four cases resolved in acute phase, 5 developed subacute and CAand 1 patient died (with Systemic Lupus Erythematosus). During follow-up ESR, hsIL-6, DAS-28 index and WHODAS2 score were higher in patients with subacute or CA compared to solved cases (p&lt;0.05). High levels of ESR and hs-IL6 at onset of ChikV infection were related with the development of CA (p&lt;0.05). High DAS 28 index and WHODAS-II score were related to development of subacute or CA (p&lt;0.05). <h3>Conclusions</h3> Fever, polyarthralgias, myalgias and rash were the main acute symptoms of ChikV fever and 50% of patients developed CA and a high disability. High levels of hsIL-6 and ESR could be used as a biomarkers to predict CA since acute phase. Inflammatory biomarkers, disability and DAS-28 remained high in subacute an CA compared to solved cases. <h3>References</h3> Schwartz O, Albert ML. Biology and pathogenesis of Chikungunya virus. Nature Rev Microbiol 2010; 8: 491500. Leparc-Goffart I, Nougairede A, Cassadou S, et al. Chikungunya in the Americas. Lancet 2014;383:514 Kautz TF, Diaz-Gonzalez EE, Erasmus JH, et al. Chikungunya Virus as cause of Febrile Illness outbreak, Chiapas, Mexico, 2014. Emerg Infect Dis 2015;21(11):2070–2073. <h3>Disclosure of Interest</h3> None declared
Latent-Membrane 2a Specific CTL’s but Not Latent-Mebrane 1 Specific CTL’s Lysis Efficiently Hodgkin Lymphoma Cells.
Authors: Max S. Topp, Jan Diekamm, Olaf Beck, Georg Rauser, Kai Hauschulz, Christina Neff, Gabriele Kuntz, Hermann Einsele
Journal: Blood (2004)
OC-052 The Impact a Public Health England (PHE) Campaign Linking Heartburn with Cancer had on a Single Endoscopy Unit in a Large Teaching Hospital: Abstract OC-052 Table 1
Authors: J Callaghan, P Boger, J Thomas, T Underwood
Journal: Gut (2016)

<h3>Introduction</h3> Public Health England (PHE) launched a ‘Be Clear on Cancer campaign on 26<sup>th</sup> January 2015 encouraging patients with heartburn to see their GP. Our aim was to analyse the impact the ‘Be Clear on Cancer’ campaign had on the number of 2 Week-Wait (2 WW) OGDs performed and the number of cancers detected. <h3>Methods</h3> A retrospective analysis of the endoscopy reporting system (HICCS) was undertaken for the 3 months after the launch of the campaign and compared to the same time period across the preceding 3 years. The outcomes considered in this analysis were any cancer of the upper GI tract or Barrett’s Oesophagus. <h3>Results</h3> The total number of OGDs (1409) in 2015 was higher than any preceding year, as was the number of 2 WW OGDs (399). The number of cancers fell in 2015 compared to preceding years with only 7 cancers detected on the 2 WW pathway, of which 2 were deemed curable after MDT discussion. The chance of detecting cancer via a 2 WW OGD fell from 6.9% in 2012 to 1.8% in 2015, with the number needed to scope (NNS) rising from 15.5 patients in 2012 to 57 patients in 2015. The tariff cost of one OGD at the time of the study was £490 leading to an estimated cost per cancer detected of just over £7500 in 2012 rising to just under £28,000 in 2015. There was an increase in the number of new cases of Barrett’s Oesophagus detected on the 2 WW pathway during the studied period from 9 in 2012 to 19 in 2015. Barrett’s Oesophagus and cancers detected outside of the 2 WW pathway are also presented in Table 1. <h3>Conclusion</h3> The PHE ‘Be Clear on Cancer’ campaign did not detect increased numbers of cancers compared to preceding years despite a large increase in the number of 2 WW OGDs performed in the studied period. Our analysis indicates that purely increasing the number of 2 WW pathway OGDs with the aim of detecting cancer is expensive and resulted in fewer cancers detected. As the absolute number of cancer cases has decreased despite a 72% increase in number of 2 WW pathway OGDs it is difficult to argue for continuing to increase the number of patients on this pathway without significant modification to the pathway. OGD is not a pleasant test, made worse for the patient by the thought that it may detect a cancer, when in real terms the chance of finding a cancer is relatively small (1.8% in 2015). <h3>Disclosure of Interest</h3> None Declared
An Unexpected Chink in the Transcriptional Armor of Plasmacytoid Dendritic Neoplasms
Authors: Maria Kleppe, Ross L. Levine
Journal: Cancer Cell (2016)

In this issue of Cancer Cell, Ceribelli et al. use functional genomic and chemical screening to reveal the existence of a TCF4/BRD4-dependent oncogenic regulatory network in blastic plasmacytoid dendritic cell neoplasm (BPDCN) and demonstrate that BPDCN cells are highly sensitive to therapeutic targeting of this novel dependency.