tbuckley/cabot-search huggingface dataset:
THU0247 What is a Risk Factor for the Knee Synovitis Recurrence after an Arthroscopic Synovectomy in a Patient with Rheumatoid Arthritis?
Authors: M. Lipina, M. Makarov, V. Amirdjanova, S. Makarov, V. Pavlov, V. Kolomacky, D. V. Goriachev, T. E. Mozhar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Arthroscopic knee synovectomy (AKS) is the most popular surgery treatment for persistent knee synovitis among patients with rheumatoid arthritis (RA). <h3>Objectives</h3> To assess the probability of knee synovitis recurrence during the postoperative period dependings upon disease activity and whether or not the patient receiveings disease–modifying anti–rheumatic drugs (DMARDs). <h3>Methods</h3> 124 AKS for 108 rheumatoid arthritis patients were made. The average period of assessment was 4.5 ± 2.5 years, the average patient’s age was 41.7 ± 14.3 years. After AKS there were clinical symptoms of synovitis recurrence in 20% of cases (25 knees), after an average period of 10.8 ± 5.1 months (i.e. from 0.5 to 2 years). The first prescription of DMARDsfor these patients was quite late: after 3.5 ± 1.8 years since the beginning of the disease. The treatment with the DMARDswas short and unsystematic. Usually patients with the synovitis recurrence were treated with methotrexate in maximum doses of 10 mg per week. 36% of the patients were treated with glucocorticoids. 28% of the patients were treated with the biological disease-modifying antirheumatic drugs (infliximab). 12.8% of the synovitis recurrence in the knees after surgery was diagnosed at the same time as the RA exacerbations. Before surgery, the disease activity in rheumatoid arthritis was high: 12.7 ± 5.4 in Routine Assessment of Pain Index Data (RAPID-3). Cox’s F-Test and Kaplan-Maier`s curve were used to determine differences in the likelihood of the synovitis recurrence, depending on the availability of therapy. Assessment of the prognostic significance of RA was made by ROC- curve analysis. <h3>Results</h3> In the case of absence of matched DMARDs by the 24th month after the surgery, the synovitis recurrence appeared in more than 80% of the patients (Cox’s F-Test = 11.69495, p&lt;10<sup>-5</sup>). For values ​​of the RAPID-3 index above 11.7 points with 86% sensitivity and 74.4% specificity predicted recurrence of synovitis in the following year. <h3>Conclusions</h3> DMARDs and high activity of RA are considered as risk factors for the knee synovitis recurrence after the AKS. <h3>Disclosure of Interest</h3> None Declared
AB0039 The Frequency of Acpa-Specific B Cells in the Circulating Memory B Cell Pool of Patients with Rheumatoid Arthritis: Table 1.
Authors: U. Saunders, T. Fassbinder, H. Becker, E. Jung, E. Mickholz, A.M. Jacobi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by the presence of autoantibodies (AA) such as rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs). These AA do not only play a pivotal role in diagnostics, but also in pathogenesis of RA. AA can be secreted by long-lived plasma cells homing to the bone marrow or by newly generated plasma cells derived from the memory B cell pool. <h3>Objectives</h3> To determine the frequency of ACPA-specific cells within the circulating memory B cell pool of ACPA-positive RA patients. <h3>Methods</h3> In order to compare the frequency of anti-cyclic citrullinated peptid (CCP) and anti-mutated citrullinated vimentin (MCV) antibody specific B cells within the memory B cell pool of 7 CCP- and 7 MCV-positive patients with RA and 4 or 6 normal healthy subjects (NHS) we analyzed antibody secretion by ELISPOT after transforming memory B cells into plasmablasts (PB). For comparison we determined the frequency of tetanus toxoid (TT)-specific B cells in the circulating pool of memory B cells of 8 TT-vaccinated NHS. CD27<sup>+</sup> memory B cells were isolated from peripheral blood samples. After polyclonal activation for 4 days the percentage of PB (CD27<sup>++</sup>) was determined by flow cytometry. To determine the frequency of anti-CCP, anti-MCV and anti-TT antibody secreting cells ELISPOT assays (IgM, IgG, IgA) were performed. <h3>Results</h3> Flow cytometric analysis revealed that after 4 days 62±11% (RA n=14) and 62±13% (NHS n=18) of all viable cells in culture adopted the phenotype of CD27<sup>++</sup> PB. The frequencies of antigen-specific B cells of all individuals are shown in Table 1. In contrast to NHS, 71.4% of CCP-positive and 28.6% of all MCV-positive RA patients had detectable frequencies of CCP- or MCV-specific IgG antibody secreting cells (ASC). In these individuals the frequencies of ACPA-secreting cells were lower than the frequency of anti-TT-specific IgG ASC in TT-vaccinated NHS, who all had detectable frequencies of TT-specific IgG ASC (CCP: 0.22±0.21%, MCV: 0.34±0.40, TT: 0.9±0.7). <h3>Conclusions</h3> Using this approach, ACPA-specific B cells can be detected in the circulating memory B cell pool only in a subset of ACPA-positive RA patients. In the remaining patients, ACPA-specific B or plasma cells might home in the bone marrow or inflamed joints. <h3>Disclosure of Interest</h3> U. Saunders Grant/research support: Chugai Pharmaceutical Co., Ltd., T. Fassbinder: None declared, H. Becker: None declared, E. Jung: None declared, E. Mickholz: None declared, A. Jacobi Grant/research support: Chugai Pharmaceutical Co., Ltd. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2229
328 PROGRAMMED DEATH 1 (PD-1) EXPRESSION OF PERIPHERAL CD4+ T LYMPHOCYTES IMPLICATES PROGRESSION OF MALNUTRITION AND HEPATIC CARCINOGENESIS IN PERSISTENT HEPATITIS C VIRAL INFECTION
Authors: P.-S. Chu, N. Nakamoto, H. Ebinuma, S. Usui, K. Sugiyama, T. Kanai, H. Saito, T. Hibi
Journal: Journal of Hepatology (2013)
Abstract 711: Small molecule compounds that target cell division cycle 7 (Cdc7) kinase inhibit cell proliferation and tumor growth.
Authors: Julie Bailis, Li Fang, Jessica Orf, Scott Heller, Tammy Bush, Matthew Bourbeau, Sonia Escobar, Michael Frohn, Paul Harrington, Faye Hsieh, Alexander Pickrell, Kelvin Sham, Aaron Siegmund, Helming Tan, Leeanne Zalameda, John Allen, Dineli Wickramasinghe
Journal: Cancer Research (2013)

Abstract Cdc7 is an essential, serine/threonine protein kinase that activates the initiation of DNA synthesis at replication origins. Cdc7 also promotes cell cycle checkpoint activation in response to replication stress. As a key regulator of S phase entry and progression, Cdc7 kinase is a potential target for cancer therapy, with a distinct mechanism of action from known drugs that inhibit DNA replication. Following a high throughput screen for inhibitors of Cdc7 kinase activity, we investigated structure-activity relationships of azole-based compounds and optimized the compounds for potency and pharmacokinetic properties. Here we present the characterization of one of these compounds as a potent, selective, bioavailable Cdc7 kinase inhibitor. In cells, Cdc7 inhibition decreases MCM2 phosphorylation and DNA synthesis, causes DNA damage, and slows S phase progression. Cdc7 inhibition also induces chromosome missegregation leading to cell lethality in vitro and tumor growth inhibition in vivo. Cdc7 inhibition provides a new approach to target cancers, either as a single agent or in combination with chemotherapy. Citation Format: Julie Bailis, Li Fang, Jessica Orf, Scott Heller, Tammy Bush, Matthew Bourbeau, Sonia Escobar, Michael Frohn, Paul Harrington, Faye Hsieh, Alexander Pickrell, Kelvin Sham, Aaron Siegmund, Helming Tan, Leeanne Zalameda, John Allen, Dineli Wickramasinghe. Small molecule compounds that target cell division cycle 7 (Cdc7) kinase inhibit cell proliferation and tumor growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 711. doi:10.1158/1538-7445.AM2013-711
Water-Loading Test in Bacteriuria
Authors: Panayiotis Papanayiotou, Anastasius S. Dontas
Journal: New England Journal of Medicine (1972)

Excretion of bacteria in the urine was measured during administration of a large water load over a two-hour period to 26 elderly subjects. Five patients had morning bacteriuria with more than 105 colonies per milliliter. Bacterial concentration and excretion rates increased during water loading in these patients and reached a peak at 60 to 100 minutes. In eight subjects excretion of bacteria was increased during diuresis. In 13 subjects with negligible base-line bacteriuria the urine became or remained negative. Renal function was impaired in both groups with frank and transient bacteriuria. The identical time course of the bacterial rise during diuresis in subjects with frank and occult bacteriuria and their similar impairment of renal function implies an upper rather than a lower urinary-tract origin of bacteriuria. The water-loading test may be useful for screening subjects with doubtful bacteriuria.
Abstract LB-19: Interaction of GPR56 with TG2 regulates melanoma progression
Authors: Liquan Yang, Scott Friedland, Sonali Mohanty, Lei Xu
Journal: Cancer Research (2012)

Abstract GPR56 is a member of a newly described adhesion G protein-coupled receptor family. We previously reported that the expression of GPR56 significantly inhibited tumor progression of human melanoma cells, and its N-terminus binds to tissue transglutaminase (TG2), a major crosslinking enzyme in ECM. To investigate the contribution of TG2 to GPR56-regulated melanoma progression, we analyzed the tumor growth of the melanoma cell line, MC-1, in the presence or absence of TG2. Our data showed that ectopic GPR56 expression abolished the influence of TG2 on tumor growth, whereas knocking down GPR56 in tumor cells dramatically enhanced TG2's tumor promoting effect. Consistently, interrupting the interaction of constitutive GPR56 with TG2 by overexpression of a free GPR56-N fragment significantly increased tumor growth. However, removing TG2 almost completely blocked tumor formation from GPR56-knocking down cells but not from control or GPR56-overexpressing cells. Collectively, our data revealed a model in which GPR56 plays dual roles during melanoma progression: it antagonizes the tumor-promoting effects of TG2 but positively regulates the tumor initiation/maintenance of melanomas. To investigate further how GPR56 might antagonize the function of TG2 in melanoma progression, we examined the expression/deposition of ECM components in cells and in tumor. Our data demonstrated that GPR56 regulates the distribution of TG2 and its partners in tumor ECM in vivo. Taken together, we present evidence here that a novel adhesion receptor, GPR56, regulates melanoma progression by modulating TG2 in the tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-19. doi:1538-7445.AM2012-LB-19
Medullary Cavity Stenosis of the Metacarpals
Authors: ARTHUR J. KENNEY, YEVGENIY S. ARSHANSKIY, LAURENCE G. HANELIN
Journal: Clinical Nuclear Medicine (1997)

Medullary cavity stenosis of the metacarpals is a normal variant of no clinical significance. its radiographic appearance consists of endosteal cortical thickening with narrowing of the medullary space of the involved metacarpals. According to the authors, the scintigraphic appearance of this variant has not been previously described.
A Photosensitive Dermatitis in the Intensive Care Unit
Authors: Marco Mercieri, Angelo Mercieri
Journal: New England Journal of Medicine (2011)

An 88-year-old man with long-standing obstructive lung disease was admitted to the intensive care unit with pneumonia and acute respiratory failure requiring mechanical ventilation. He was noted to have a symmetric, scaly, sunburn-like, hyperpigmented rash extending from his hands to a clearly demarcated border midway up the arm, suggesting a photosensitive distribution in a patient accustomed to wearing short sleeves. He had no history of diarrhea or dementia before his admission. Dietary habits were reported to be poor. Serum niacin levels were low (<0.5 ng per milliliter; normal range, 0.5 to 15 ng per milliliter), and a cutaneous biopsy showed . . .
AB0240 Prevalence and severity of systemic vasculitis in various organs of patients with progressive system:
Authors: M. Bély, Ά. Apáthy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The aim of this study was to determine: the <i>prevalence</i> and <i>severity</i> of <i>systemic vasculitis</i> (SV) with or without <i>fibromuscular and/or intimal proliferation</i> (FIP) <i>in various organs</i> of SSc patients. <h3>Methods</h3> 12 organs (heart, lungs, liver, spleen, kidneys, pancreas, gastrointestinal tract, adrenal glands, skeletal muscle, peripheral nerve, skin and brain) of 11 patients (female 10, average age 53.6 years; male 1, age of 65 years) with SSc was studied. SSc was confirmed clinically according to the criteria of the ACR. The <i>prevalence</i> of SV with or without FIP in blood vessels of various organs was determined histologically. The “severity” of vasculitis was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale. <h3>Results</h3> SV with or without FIP was present in all organs (100%) of 11 SSc patients. SV involved several and in some organs only very few blood vessels of different size (including capillaries). The severity of vasculitis (the number of involved vessels) in various organs was diverse. Severity of systemic vasculitis in various organs is summarized in Table 1. <h3>Conclusions</h3> The basic pathological process in SSc is systemic <i>non-specific</i> or <i>fibrinoid necrotic vasculitis</i> with or without FIP. SV will be accompanied by focal, multifocal (more or less confluent) or diffuse progressive interstitial fibrosis and sclerosis, depending on the stage of the disease, involving various organs with different severity. The high prevalence of SV with or without FIP and the consecutive fibrosis of the kidney, spleen, lung, pancreas, or heart identify the main targets of autoimmune processes in SSc prior to the more visible skin involvement. The mortality of SSc depends on the localization of SV - with or without FIP - and consecutive fibrosis. Involvement of the kidneys, heart and lung is the most frequent cause of a lethal outcome. Although the pancreas, spleen and gastrointestinal tract, as well as the skin are always involved at death, they are less critical targets of SV. This finding is supported by our previous study in which the leading causes of death were uremia (in 6 of 11 patients due to complex nephropathy) or circulatory failure (in 5 of 11 patients due to endo-myocardial fibrosis or myocardiocytolysis - with or without honeycomb lung). The high prevalence of SV and FIP in the pancreas may cause multifocal acute <i>pancreatitis</i> without lethal outcome. The high prevalence of SV and FIP in the G-I tract (with consecutive sub- mucosal fibrosis) denotes a good site for histological diagnosis of SSc, like the skin biopsy. <h3>References</h3> Apáthy Άgnes, Bély M: Mortality and histological characteristics of SSc - A retrospective study of 12 autopsy patients (Abstract). Annals Rheum Dis 2007 (Suppl II), 66:198-199. Available from: http://www.abstracts2view.com/eular/ <h3>Disclosure of Interest</h3> None Declared
Abstract 15: Association of topoisomerase II expression and cancer-specific death in patients with surgically-resected clear cell renal cell carcinoma.
Authors: Richard W. Joseph, Dan Serie, Tracy Hilton, Mansi Parasramka, Jeanette Eckel-Passow, John Cheville, Bradley C. Leibovich, Alexander S. Parker
Journal: Cancer Research (2013)

Abstract PURPOSE: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. METHODS: We identified 947 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/16/1990 and 9/27/2006. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features we employed Kruskal-Wallis tests and for associations with cancer-specific survival we generated Cox proportional hazard regression models. RESULTS: Higher TOP2a expression is associated with later stage, higher grade and higher Mayo SSIGN score (all p &amp;lt; 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend &amp;lt; 0.0001). Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.31 95% CI 1.64-3.25; p&amp;lt;0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ∼95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.09 95% CI 1.29-7.40; p =0.01). CONCLUSION: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients. Citation Format: Richard W. Joseph, Dan Serie, Tracy Hilton, Mansi Parasramka, Jeanette Eckel-Passow, John Cheville, Bradley C. Leibovich, Alexander S. Parker. Association of topoisomerase II expression and cancer-specific death in patients with surgically-resected clear cell renal cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 15. doi:10.1158/1538-7445.AM2013-15
Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry
Authors: J Trka, M Kalinová, O Hrušák, J Zuna, O Krejčí, J Madžo, P Sedláček, V Vávra, K Michalová, M Jarošová, J Starý
Journal: Leukemia (2002)
Abstract SY11-01: Plasma tumor DNA: Changing the paradigm for administering systemic therapies.
Authors: Julia A. Beaver, Patricia Valda, Danijela Jelovac, Michaela J. Higgins, Ben H. Park
Journal: Cancer Research (2013)

Abstract The ability to accurately detect somatic cancer DNA alterations from cell free circulating plasma tumor DNA (ptDNA) using next generation genomic technologies has many potential applications for clinical oncology. The initial use of this technology has been to detect point mutations in peripheral blood that could serve as predictors of response to various targeted therapies. Thus the development of a “liquid biopsy” that could easily match the mutational status of a given cancer with a specific therapy had great therapeutic implications. For example, the ability to assess certain epidermal growth factor receptor (EGFR) mutations via blood versus an invasive lung biopsy would allow for the rapid determination of whether a patient would be a candidate for small molecule EGFR inhibitors such as gefitinib or erlotinib. We initially sought to evaluate the feasibility of detecting PIK3CA mutations in circulating ptDNA from patients with metastatic breast cancer using a novel technique of digital polymerase chain reaction (PCR) called BEAMing (for Beads, Emulsions, Amplification, Magnetics). We demonstrated that BEAMing is both sensitive and specific for identifying PIK3CA mutations in metastatic breast cancer patients, though we also confirmed the work of other groups that PIK3CA mutation status can change with progression to metastatic disease. An overview of these data will be presented. While these studies demonstrated the feasibility of using ptDNA in metastatic patients as a liquid biopsy for detecting specific cancer mutations, we are now focusing efforts to exploit the quantitative nature of digital PCR technology. Specifically, by analyzing the amount of ptDNA before and after primary breast surgery in early stage breast cancer patients, we will identify which patients truly have residual microscopic disease post surgery and therefore would be the most appropriate candidates for additional systemic therapies. Thus, in contrast to the current paradigm of “over” treating breast cancer patients in the adjuvant setting, detection of ptDNA using next generation digital PCR technologies will enable us to make rational decisions regarding which patients truly have need for adjuvant systemic therapies. Preliminary data and ongoing studies will be discussed as well as the implementation of these technologies in future clinical trials. Citation Format: Julia A. Beaver, Patricia Valda, Danijela Jelovac, Michaela J. Higgins, Ben H. Park. Plasma tumor DNA: Changing the paradigm for administering systemic therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY11-01. doi:10.1158/1538-7445.AM2013-SY11-01