tbuckley/cabot-search huggingface dataset:
THU0348 Assessment of Submandibular Gland Ultrasonography in Early-Stage Sjögren's Syndrome
Authors: N. Hashimoto, S. Uchiyama, M. Kitano, T. Nakazawa, T. Iwasaki, T. Hashimoto
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Sjögren9s syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocyte infiltration in salivary and lacrimal glands. Recently, salivary gland ultrasonography proved valuable for the assessment of salivary gland involvement in SS and seemed to exhibit good diagnostic properties. We previously reported that submandibular gland ultrasonography (SGUS) is a useful noninvasive and inexpensive procedure for the evaluation of the structural changes of salivary gland involvement in SS patients (International Symposium on SS 2002, EULAR 2009, EULAR 2012, EULAR 2015). However, the usefulness of SGUS for the evaluation of early-stage SS patients with normal salivary flow was unknown. <h3>Objectives</h3> The aim of this study was to examine the usefulness of SGUS in early-stage SS patients with normal salivary flow. <h3>Methods</h3> We observed 9 non-SS patients with anti-SS-A antibodies sero-positive, 13 SS patients with low salivary flow (L/SS) and 16 SS patients with normal salivary flow (N/SS). SS was diagnosed according to the American College of Rheumatology (ACR) classification criteria for SS. SS was divided into two groups according to salivary flow using Gum test [L/SS (≤10mL/10min) and N/SS (&gt;10mL/10min)]. All patients were examined RF, FANA, anti-SS-A/SS-B antibodies in serum and labial salivary gland biopsies for the diagnosis of SS. All patients were performed US scans by a single examiner who was blinded to the clinical data and used an US with a 7.5-MHz liner array transducer (SSA-350A; Toshiba, Tokyo, Japan). US staging scores were assessed by glandular size, inhomogeneity and contrast of diagastric muscle (0: normal, 1: mild, 2: moderate, 3: severe structural damage). PD grading scores were graded by pulsed wave pattern in power Doppler US at the internal SG facial arteries (0: normal, 1: intermittent wave pattern, 2: disappearance of wave pattern). <h3>Results</h3> The whole salivary flow was significantly decreased in L/SS (4.4±2.8mL/10min) patients than in non-SS (19.0±7.6mL/10min, p&lt;0.001) and N/SS (19.1±8.0mL/10min, p&lt;0.001) patients. All patients were anti-SS-A antibodies sero-positive. There were no significant differences among non-SS, N/SS and L/SS patients in the frequency of sero-positive antibodies such as RF, FANA and anti-SS-B. However, the size of SG was significantly smaller in L/SS (216.1±59.7mm<sup>2</sup>) than in non-SS (325.9±66.2mm<sup>2</sup>, p&lt;0.005) and N/SS (311.3±98.7 mm<sup>2</sup>, p&lt;0.005). US staging scores and PD grading scores were significantly higher in L/SS (2.85±0.38, 1.62±0.51) than in non-SS (0.89±1.05, 0.33±0.71, p&lt;0.001) and N/SS (1.44±1.15, 0.44±0.51, p&lt;0.001) patients. <h3>Conclusions</h3> SUSG findings reflect salivary gland functions and is useful for the diagnosis of SS with low salivary flow but not for early-stage of SS patients with normal salivary flow. <h3>Disclosure of Interest</h3> None declared
Hydroxychloroquine prescribing and monitoring practices among Irish dermatologists and rheumatologists
Authors: E. Gilhooley, C. Feighery, S.M. Collins
Journal: British Journal of Dermatology (2016)

Hydroxychloroquine (HCQ) is an effective drug that is widely used to treat connective tissue and autoimmune diseases. Overall, it has an excellent safety profile; however, its most potentially serious and irreversible side-effect is retinal toxicity. The Royal College of Ophthalmologists (RCO) published their recommendation on HCQ and ocular toxicity screening in 2009.

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PTU-014 Relationship between Ferritin/MCV and GI Pathology in Patients Referred from Primary Care with Iron Deficiency Anaemia: Abstract PTU-014 Table 1
Authors: E Atallah, S Kumar, S Chatharoo, A Agrawal
Journal: Gut (2016)

<h3>Introduction</h3> Iron deficiency anaemia (IDA) is common with BSG guidance suggesting Gastrointestinal (GI) blood loss from colonic or gastric cancer, and malabsorption in coeliac disease are the most important causes.<sup>1 </sup>Serum ferritin, microcytosis and hypochromia are the most sensitive markers for iron deficiency.<sup>2 </sup>Our objective was to investigate the correlation between MCV/ferritin and GI pathology in patients with IDA by comparing GI pathology in patients with low ferritin versus normal ferritin; and in patients with microcytosis versus normocytosis. <h3>Methods</h3> Retrospective cohort study for consecutive patients who had undergone bi-directional endoscopy and/or GI imaging to investigate unexplained anaemia were included. Data was retrieved including Hb, MCV, folate, B12, co-morbidities and findings at endoscopy, histology and imaging were recorded. Patients with normal haemoglobin as per our laboratory’s cut off were excluded. Included patients were stratified according to serum ferritin and MCV into 2 groups (low/normal) for each marker. We used the cut-off concentration as per our local laboratory (10 µg/l for ferritin and 78 FL for MCV). The outcome assessed was any GI pathology found that may explain the IDA. Data was analysed including and excluding the diagnosis of gastritis/oesophagitis as possible GI causes of anaemia. <h3>Results</h3> 265 included patients (mean age: 68; range: 16–91 years old; 124 males and 141 females) had undergone GI investigations for IDA. Of these, 84 patients had low ferritin (31.6%) whereas 181 patients had normal ferritin. GI pathology excluding gastritis/oesophagitis occurred in 40 (47.6%) and 68 (37.5%) patients in low and normal ferritin group respectively. P = 0.12. Based on MCV, 96 patients had low MCV (36.2%) whereas 169 patients had normal MCV. GI pathology occurred in 38 patients in low MCV group (39.5%) and in 70 patients with normal MCV (41.4%), P = 0.76. No differences were noted upon including gastritis/oesophagitis. <h3>Conclusion</h3> There was no clinical or statistical difference in GI pathology in patients presenting with anaemia with or without evidence of iron deficiency. Although a significant number of patients had a GI workup despite no evidence of iron deficiency, the lesion pickup was similar in both groups. Therefore, our study demonstrates the MCV/ferritin might be sensitive markers for IDA but they don’t correlate with GI pathology. <h3>References</h3> 1 <i>Gut</i> 2011;<b>60</b>:1309e–1316. doi:10.1136/gut.2010.228874 2 Prevalence of hypochromia vs microcytosis in iron deficiency. <i>Clin Lab Haematol</i> 2000;<b>22</b>:79e80. <h3>Disclosure of Interest</h3> None Declared
The Impact of Outcome and Hepatic Toxicity in HCV-Infected Patients with Diffuse Large B-Cell Lymphoma Treated with Rituximab Plus CHOP Therapy; A Retrospective Multicenter Japanese Analysis.
Authors: Daisuke Ennishi, Yoshinobu Maeda, Nozomi Niitsu, Minoru Kojima, Koji Izutsu, Jun Takizawa, Shigeru Kusumoto, Masataka Okamoto, Masahiro Yokoyama, Yasushi Takamatsu, Kazutaka Sunami, Akira Miyata, Kayoko Murayama, Akira Sakai, Morio Matsumoto, Katsuji Shinagawa, Akinobu Takaki, Keitaro Matsuo, Tomohiro Kinoshita, Mitsune Tanimoto
Journal: Blood (2009)
Conditioning Intensity in Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Ulrike Bacher, Evgeny Klyuchnikov, Jeanette Carreras, Jennifer Le-Rademacher, Ginna G. Laport, Silvia Montoto, David G. Maloney, Parameswaran Hari
Journal: Blood (2011)
The Importance of Pharmacogenomic Variations in the Treatment of Children with Acute Lymphoblastic Leukemia
Authors: Chung-Yi Hu, Sheng-Kai Chang, Yung-Li Yang, Shu-Wha Lin, Rong-Jing Chiu, Kai-Hsin Lin, Shiann-Tarng Jou, Meng- Yao Lu, Hsiu-Hao Chang, Kuo-Sin Lin, Dong-Tsamn Lin
Journal: Blood (2008)
Alemtuzumab and Rituximab for Initial Treatment of High Risk, Early Stage Chronic Lymphocytic Leukemia (CLL).
Authors: Clive S. Zent, Timothy G. Call, Tait D. Shanafelt, Diane F. Jelinek, Renee C. Tschumper, Charla R. Secreto, Deborah A. Bowen, Susan M. Geyer, Brian F. Kabat, Betsy R. LaPlant, Wenting Wu, Neil E. Kay
Journal: Blood (2007)
The Impact of Pre-Transplant Depression on Outcomes of Allogeneic and Autologous Hematopoietic Stem Cell Transplantation
Authors: Areej El-Jawahri, Yi-Bin Chen, Ruta Brazauskas, Naya He, Stephanie J. Lee, Jennifer M Knight, Theresa Hahn, Nandita Khera, Jignesh D Dalal, Carmem Bonfim, Yoshiko Atsuta, Wael Saber
Journal: Blood (2015)
Multiplicative Interaction Between Mean Corpuscular Volume and Red Cell Distribution Width in Predicting Mortality of Elderly Patients with and without Anemia
Authors: Anthony P. Lam, Krishna Gundabolu, Ashwin Sridharan, Rishi Jain, Pavlos Msaouel, Grigorios Chrysofakis, Yiting Yu, Ellen W. Friedman, Elizabeth Price, Stanley L. Schrier, Amit Verma
Journal: Blood (2012)
THU0280 IL-12 Exacerbates Sjogren's Syndrome through Inducing Lymphocyte Infiltrations into Salivary Glands and Imbalance of Lymphocyte Subsets
Authors: B. Shi, J. Qi, R. Feng, Z. Zhang, W. Chen, W. Li, X. Tang, G. Yao, L. Sun
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Primary Sjogren9s syndrome (pSS) is characterized by inflammation of exocrine glands and functional impairment of the salivary and lacrimal glands, accompanied by the disorders of immune system, including increased pro-inflammatory cytokines, decreased anti-inflammatory cytokines, and turbulence of immune cell homeostasis. IL-12 is a pro-inflammatory cytokine relating to autoimmune diseases. However, the role of IL-12 in pSS and the underlying mechanism is still not fully understood. <h3>Objectives</h3> We aimed to explore the role of IL-12 in the pathogenesis of pSS. <h3>Methods</h3> Serum IL-12 was detected in pSS patients and healthy controls. The percentages of T cell subsets, B cells and plasma cells in peripheral blood were analyzed. NOD mice (experimental Sjogren9s syndrome model, ESS) were treated with recombinant IL-12 protein, anti IL-12 MAb or same volume of saline, respectively. One week later, the salivary flow rate was detected. Histopathology of submandibular gland, lacrimal gland, lung and kidney were observed by HE staining. Immunochemistry was performed to identify the phenotype of the infiltrated lymphocytes. Flow cytometry was used to detect the proportion of lymphocyte subsets of splenocytes. <h3>Results</h3> IL-12 levels were significantly higher in pSS patients. Th1, Th17 and Tfh cell percentages were significantly higher in pSS, while Treg percentage was decreased. Th1/Th2 and Th17/Treg ratios were also higher in pSS patients. Besides, plasma cell percentages were also higher in pSS patients. All of the above data suggested the disturbance of both cellular and humoral immune balances in pSS patients. In vivo IL-12 treatment in NOD mice significantly increased salivary gland swollen severity, decreased salivary flow rates, and promoted lymphocyte infiltration in salivary glands, pulmonary interstitium and renal medulla. Immunochemistry staining showed that most of the infiltrated lymphocytes into the organs were CD4+, and a majority of the CD4+ cells were IL17A+, suggesting IL-12 induced Th17 cell infiltrations in multiple organs of NOD mice. On the other hand, anti IL-12 decreased the percentages of Th1, Th17 and Tfh cells, and corrected the imbalance of Th1/Th12 and Th17/Treg ratio. The anti IL-12 also reduced the salivary gland swollen and lymphocyte infiltration, whilst increased salivary flow rates. <h3>Conclusions</h3> IL-12 deteriorated the pathogenesis of ESS partially by promoting lymphocyte infiltration into the affected organs and disturbance of lymphocyte subsets. Targeting IL-12 may be a potential therapeutic strategy for SS patients. <h3>Disclosure of Interest</h3> None declared
Characteristics and Prognostic Significance of CRLF2 High Expression and the Co-Existence with JAK1 Mutations and Ikaros Deletion in Adult Acute Lymphoblastic Leukemia
Authors: Zheng Ge, Juan Liu, Run Zhang, Xing Guo, Jing-Yan Xu, Min Li, Chun Qiao, Jian-Yong Li
Journal: Blood (2014)
Potent Immunomodulatory Drug Lenalidomide Synergistically Enhance the Effect of Dendritic Cell Vaccination on Multiple Myeloma in Mouse Model,
Authors: Thanh-Nhan Nguyen-Pham, Huong Thi Thanh Tran, Sung-Hoon Jung, Jae-Sook Ahn, Deok-Hwan Yang, Tai Ju Hwang, Hyeoung-Joon Kim, Je-Jung Lee
Journal: Blood (2011)
Are the Pfa-100® Closure Time and the Skin Bleeding Time Useful in the Diagnostic Work-Up of Patients with Bleeding Diathesis? Correlation with the Severity of Bleeding Symptoms and Sensitivity for Known Defects of Primary Hemostasis.
Authors: GianMarco Podda, Paolo Bucciarelli, Federico Lussana, Marco Cattaneo
Journal: Blood (2004)
A Novel Function of CD26-Mediated Costimulation in the Cytotoxic Activity of Human CD8+ T Cells in Xenogeneic Chronic Graft-Versus-Host Disease (cGVHD) and GVL Mice Model.
Authors: Ryo Hatano, Kei Ohnuma, Taketo Yamada, Wataru Takasawa, Yuko Endo, Yumiko Matsumura, Osamu Hosono, Nam H. Dang, Chikao Morimoto
Journal: Blood (2009)
The Frequency, Diversity, and Function of Human T-Cell Leukemia Virus Type 1-Specific CD8+ T-Cell Is Reduced in Adult T-Cell Leukemia Patients.
Authors: Tomohiro Kozako, Masaki Akimoto, Izumi Masamoto, Makoto Yoshimitsu, Kakushi Matsushita, Shinsuke Suzuki, Kimiharu Uozumi, Naomichi Arima
Journal: Blood (2006)
A Novel Bispecific CD38 Antibody Eradicates Multiple Myeloma in a Mouse Model Following Yttrium-90-DOTA Capture
Authors: Damian J Green, Jon C Jones, Yukang Lin, Shani L. Frayo, Aimee L Kenoyer, Shyril O'Steen, Arianna Peters, Sofia HL Frost, Johnnie J. Orozco, Ajay K Gopal, Mark D Hylarides, Darrell R Fisher, Brenda M. Sandmaier, Brian G. Till, Ethan R Balkin, Don K Hamlin, D.Scott Wilbur, Kelly D Orcutt, K. Dane Wittrup, Oliver W. Press
Journal: Blood (2015)
Comparison of Empiric Versus Prophylactic Administration of Ceftazidime during Neutropenia Associated with Reduced-Intensity Allogeneic Stem Cell Transplantation (RIST).
Authors: Kyle M. Donley, Juan C. Gea-Banacloche, Robert M. Dean, Seth M. Steinberg, Richard W. Childs, Jeanne Odom, Kathleen Castro, Tracey Chinn, Daniel H. Fowler, Michael R. Bishop
Journal: Blood (2004)
Frequent Detection of C-Cbl Homozygous Mutation in Secondary Myelogeneous Leukemia Transformed from MDS/MPD with Chromosome 11q Uniparental Disomy
Authors: Hideki Makishima, Andrew J Dunbar, Anna M Jankowska, Lukasz P. Gondek, Eric D Hsi, Michael A McDevitt, Alan F. List, Jaroslaw P. Maciejewski
Journal: Blood (2008)
Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions
Authors: Marc Arbyn, Lan Xu, Freija Verdoodt, Jack Cuzick, Anne Szarewski, Jerome L. Belinson, Nicolas Wentzensen, Julia C. Gage, Michelle J. Khan
Journal: Annals of Internal Medicine (2016)

High-risk human papillomavirus (hrHPV) testing to triage women with minor cervical lesions generates many referrals.
The Incidence of Atrial Fibrillation Among Patients with AL Amyloidosis Undergoing High Dose Melphalan and Stem Cell Transplantation (HDM/SCT): Experience at a Single Institution
Authors: Dina Brauneis, Monica Arun, Frederick L Ruberg, Anthony C Shelton, John Mark Sloan, Karen Quillen, Vaishali Sanchorawala, Cindy Varga
Journal: Blood (2015)
PWE-028 A Novel Assay for The Direct Detection of Deoxythioguanosine (DTG) in DNA from Patients On Azathioprine Using Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS)
Authors: S Coulthard, P Berry, S McGarrity, C Redfern
Journal: Gut (2016)

<h3>Introduction</h3> The correlation between thiopurine drug metabolite levels in red blood cells (RBC) and clinical response is currently under debate, with some studies reporting a good correlation whereas others report a poor correlation. However, without a suitable alternative assay this is the only method presently available to guide dosing of patients treated with thiopurine drugs: azathioprine (AZA), mercaptopurine (MP) or thioguanine. Biologically, this method is not perfect given that RBC lack the critical drug-metabolising enzyme inosine-monophosphate dehydrogenase, which is central to the bioconversion of MP to thioguanine nucleotides that are then incorporated as fraudulent bases into nucleic acids. To try to get a better indicator of drug response and hence clinical outcome, we have developed a sensitive liquid chromatography- tandem mass spectrometry (LC-MS/MS) assay to measure incorporated dTG in the DNA isolated from peripheral blood mononuclear cells of patients treated with thiopurines <h3>Methods</h3> DNA was isolated from blood samples collected from IBD patients on thiopurines. DNA was denatured then digested using P1 nuclease followed by treatment with alkaline phosphatase and finally diluted in MilliQ water prior to analysis. A total of 0.2 μg of DNA in 50 µL was injected for chromatographic separation followed by analysis on an API4000 triple quadrupole mass spectrometer. Standard curves and controls were validated and samples analysed to determine number of moles of dTG/105<sup>5</sup> moles of dA. <h3>Results</h3> From a small cohort of 20 AZA treated IBD patients (10 Crohn's Disease and 10 Ulcerative Colitis) with dTG levels of 0.18 to 11.3 moles dTG/105<sup>5 </sup>moles dA (approximately 5 to 340 femtomoles/μg DNA) were detected with no detectable dTGs in un-treated patients. The intra- and inter-assay variability was below 7.8% and 17.0% respectively with a detection limit of 15.5 pg (54.7 femtomoles) and was quantified in DNA samples relative to endogenous dA. <h3>Conclusion</h3> This method enables the direct detection of a cytotoxic thiopurine metabolite in an easily obtainable, stable sample and will facilitate a better understanding of the mechanisms of action of these inexpensive yet effective drugs. <h3>Disclosure of Interest</h3> None Declared
AB0515 Vitamin D, IL-10, IL-17, and IL-23 as Biomarker for Disease Activity in Systemic Lupus Erythematosus
Authors: T. Senturk, B. Genc Cetin, G. Sargin, N. Aydin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune, inflammatory disease and the prototype of multisystem autoimmune diseases. Several cytokines such as interleukin (IL)-10, IL-17, IL-23, and vitamin D have been suspected in the pathogenesis of SLE. However, the association between these cytokines, vitamin D and disease activity is unknown. <h3>Objectives</h3> We aimed to determine the association between IL-10, IL-17, IL-23, vitamin D and SLE disease activity index (SLEDAI) score. <h3>Methods</h3> We included 40 patients with SLE (mean age: 35.5±13.41 years, 95% female) and 20 healthy controls (mean age: 36.1±14.76 years, 70% female) in the study. Clinical and laboratory parameters and, SLEDAI score were evaluated. Serum IL-10, IL-17 and IL-23 were measured by nephelometry and vitamin D by HPLC (high-performance liquid chromatography). Mann-Whitney U and Kolmogorov-Smirnov test were used for statistical analysis. P&lt;0.05 was accepted as statistically significant. <h3>Results</h3> The level of vitamin D was significantly lower (p=0,003), and IL-23 was significantly higher (p=0,001) in SLE patients compared to healthy controls. There was no significant difference for IL-10 and IL-17 between both group (p&gt;0,05). However, a significant correlation between vitamin D and disease duration (p=0,02), and between IL-23 and vitamin D (p=0,019) were found among SLE patients. Vitamin D levels were correlated with SLEDAI score and IL-23 in patients group. <h3>Conclusions</h3> Although there are studies suppporting the role of IL-10 and IL-17 in the pathogenesis of SLE in the literature, there was no significant difference between patients and healthy controls in our study. IL-23 levels were significantly higher, whereas vitamin D levels were significantly lower in SLE patients than in the control group. Also vitamin D levels were negative correlated with duration of disease and IL-23. Levels of IL-23 may be used to evaluated the disease activity, or may be a promising therapeutic approach for SLE patients. <h3>Disclosure of Interest</h3> None declared
Cyclin D mediates tolerance of genome-doubling in cancers with functional p53
Authors: A. Crockford, L.P. Zalmas, E. Grönroos, S.M. Dewhurst, N. McGranahan, M.E. Cuomo, V. Encheva, A.P. Snijders, J. Begum, S. Purewal, J. Cerveira, H. Patel, M.J. Renshaw, C. Swanton
Journal: Annals of Oncology (2016)

BackgroundAneuploidy and chromosomal instability (CIN) are common features of human malignancy that fuel genetic heterogeneity. Although tolerance to tetraploidization, an intermediate state that further exacerbates CIN, is frequently mediated by TP53 dysfunction, we find that some genome-doubled tumours retain wild-type TP53. We sought to understand how tetraploid cells with a functional p53/p21-axis tolerate genome-doubling events.MethodsWe performed quantitative proteomics in a diploid/tetraploid pair within a system of multiple independently derived TP53 wild-type tetraploid clones arising spontaneously from a diploid progenitor. We characterized adapted and acute tetraploidization in a variety of flow cytometry and biochemical assays and tested our findings against human tumours through bioinformatics analysis of the TCGA dataset.ResultsCyclin D1 was found to be specifically overexpressed in early but not late passage tetraploid clones, and this overexpression was sufficient to promote tolerance to spontaneous and pharmacologically induced tetraploidy. We provide evidence that this role extends to D-type cyclins and their overexpression confers specific proliferative advantage to tetraploid cells. We demonstrate that tetraploid clones exhibit elevated levels of functional p53 and p21 but override the p53/p21 checkpoint by elevated expression of cyclin D1, via a stoichiometry-dependent and CDK activity-independent mechanism. Tetraploid cells do not exhibit increased sensitivity to abemaciclib, suggesting that cyclin D-overexpressing tumours might not be specifically amenable to treatment with CDK4/6 inhibitors.ConclusionsOur study suggests that D-type cyclin overexpression is an acute event, permissive for rapid adaptation to a genome-doubled state in TP53 wild-type tumours and that its overexpression is dispensable in later stages of tumour progression.