tbuckley/cabot-search huggingface dataset:
OP0192 Early Treatment-Naive Rheumatoid Arthritis (RA) is Characterised by Qualitative Changes of the INKT Regulatory Cell Repertoire
Authors: S. Mansour, A. Tocheva, M. Edwards, L. Goulston, H. Platten, C. Parsons, C. Edwards, C. Cooper, S.D. Gadola
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Innate mechanisms of inflammation control are central to the pathogenesis of autoimmune diseases (AID), including RA. Invariant Natural Killer T cells (iNKT) are a highly conserved T-cell subset with key roles in immune tolerance. iNKT-targeting therapeutic approaches are highly effective in animal models, but translation to human AID has not yet succeeded. <h3>Objectives</h3> We have previously defined the human iNKT repertoire according to the clonal distribution of high- and low-affinity iNKT T-cell receptors<sup>1</sup>. Here we have investigated the iNKT repertoire with regard to function and T-cell receptor affinity in early Rheumatoid Arthritis. <h3>Methods</h3> 100 early RA patients and 50 matched healthy people were included. Multiple iNKT clones from patients and controls were generated and analysed for TCR affinity to the restriction element human CD1d by using different CD1d/ligand-tetramers; Clones were analysed for cytokine secretion in response to CD1d/antigen and mitogen stimulation; iNKT frequency and CD1d expression on antigen presenting cells were determined by FACS; in vitro expansion of iNKT cells to antigen-pulsed autologous monocytes and recombinant CD1d/antigen coated beads was compared to differentiate inherent iNKT cell defects from defects in antigen presentation. <h3>Results</h3> The clonal repertoire of iNKT cells in healthy controls shows a broad distribution with regard to iNKT receptor affinity for CD1d. In contrast, the repertoire is highly significantly shifted towards lower-affinity iNKT clones in age-matched early RA. This shift correlates with DAS28. Analysis of untreated vs treated early RA patients shows that the iNKT repertoire is "restored to normal" in the DMARD group, and this correlates with DAS28. CD1d expression on antigen-presenting cells was not different between groups. iNKT cells in all early RA patients exhibited a bias in cytokine secretion towards Th1 cytokines, independent of CD1 antigen processing. <h3>Conclusions</h3> This is the first demonstration of changes in a T-cell compartment based on TCR-affinity during disease. The repertoire of iNKT cells in blood is significantly changed in early treatment-naive RA, with loss of higher-affinity iNKT TCR bearing cells that may have key roles in immunological tolerance. Our findings are relevant for all iNKT cell targeting approaches in humans, including those designed for restoring tolerance in AID, and also those designed for promoting inflammation in cancer or infection. <h3>References</h3> Matulis G, et al. PLoS Biol. 2010; 22;8(6):e1000402. doi: 10.1371/journal.pbio.1000402. <h3>Acknowledgements</h3> Funded by Arthritis Research UK (to SDG) <h3>Disclosure of Interest</h3> None Declared
THU0384 Spontaneous panniculitis (weber-christian disease): Clinical course variants
Authors: B.S. Belov, O.N. Egorova, O.V. Pushkova, Y.A. Karpova, S.G. Radenska-Lopovok
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Spontaneous panniculitis (SP) is a rare, little studied chronic inflammatory disease, which belongs to a group of connective tissue diseases. The variety of clinical symptoms of SP causes difficulties in diagnostics and adequate treatment. <h3>Objectives</h3> To study distinctive features of SP treatment as of today. <h3>Methods</h3> We studied 28 SP patients (26 women, 2 men), age 30-74, duration of disease 8.1±2.4 years. In addition to general clinical examination we determined the level of <i>α1-antitrypsin</i>, amylase, lipase, <i>ferritin, creatine phosphokinase</i>, we also carried out chest CT scan, <i>ultrasound scan of the node and pathomorphology study</i> of <i>skin biopsy specimen taken from the area of the node</i>. <h3>Results</h3> 29% of patients had a subacute disease and 64% of patients had a chronical disease. SP featured multiple (17 patients) painful (VAS intensity of 69±24.2 mm) nodes, mostly concentrated on the lower (26) and upper (14) extremities, less frequently the nodes were found on the chest, abdomen and face (5). 36% of cases were identified as nodule panniculitis characterized with isolated well-defined nodes, i.e. bright pink indurations of up to 5 cm in diameter. Plaque panniculitis, developed due to conglomeration of individual nodes into a red-purple nodular lesion, was identified in 46% of patients. In case of infiltration panniculitis (18%) individual bright crimson nodes or conglomerates discharged yellow oily material simulating an abscess. In 69% of cases the occurrence of nodes was accompanied with fever, polyarthralgias, myalgias and accelerated ESR, which was the same as in case of plaque and infiltrating panniculitis. Histological examination confirmed the subcutaneous fat (SCF) damage such as infiltration of lymphocytes contaminated with a few Tutton cells and lipophages. Ultrasonic scanning of skin made it possible to identify well-defined lobulation characterized with higher echodensity with an anechogenic circle. Treatment depended on the type and the state of the disease. It included nonsteroidal anti-inflammatory (13), antioxidant (28), aminoquinoline (10), glucocorticoid (18) and cytostatic (18) drugs. Due to the treatment there was a positive dynamics in 64% of cases for patients with nodule (10) and plaque (8) panniculitis. <h3>Conclusions</h3> SP is a rare recurrent polisyndrom disease which is basically caused by SCF damage. The variety of forms of the disease requires well-defined approaches to verification of the diagnosis and differentiated treatment. <h3>Disclosure of Interest</h3> None Declared
A COMPARISON BETWEEN CONVENTIONAL CONTRAST-INDUCED NEPHROPATHY AND NOVEL DEFINITION (KIDNEY DISEASE: IMPROVING GLOBAL OUTCOMES) TO PREDICT CARDIOVASCULAR RISKS IN PATIENTS WITH ACUTE CORONARY SYNDROME UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Ippei Watanabe, Rine Nakanishi, Shingo Matsumoto, Shintaro Dobashi, Takayuki Yabe, Ryo Okubo, Hideo Amano, Mikihito Toda, Takanori Ikeda
Journal: Journal of the American College of Cardiology (2016)
OP0123 Can We Use Ultrasound to Identify Rheumatoid Arthritis Patients in Remission Who Can Taper Their Medication?: Table 1.
Authors: M. van der Ven, M. Kuijper, A. Gerards, I. Tchetverikov, A. Weel, J. van Zeben, M. Hazes, J. Luime
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tapering of medication in rheumatoid arthritis (RA) patients is becoming increasingly important due to the effectiveness of both biological therapy and tight-controlled treatment. Patients are able to reach the state of remission in which they may be able to taper their medication. Whom to taper and when to taper (amount of time in remission) is unclear. Ultrasound (US) data from cross-sectional studies suggest that the presence of subclinical synovitis might increase the risk of disease flare preventing patients to be tapered. <h3>Objectives</h3> To describe the frequency of flare and to relate this to the presence of subclinical synovitis measured by US in RA patients that continue synthetic and biological DMARDs for 3 months while being in remission. <h3>Methods</h3> Patients who are participating in the TARA study and were examined by US were selected for this analysis. TARA is a single blinded randomized controlled trial that includes RA patients (aged &gt;17 years) who are treated with the combination of a synthetic DMARD and adalimumab or etanercept and are in remission (DAS44 &lt;2.4 &amp; SJC ≤1). In the first 3 months of this study patients continue their medication and if they maintain their disease state, are randomized to (i) tapering the synthetic DMARD or (ii) tapering their TNF blocker. US examination included 26 joints (MCP2-5, PIP2-5, wrists, MTP2-5) graded on greyscale (GS; 0-3) and power Doppler (PD; 0-3). A joint with subclinical synovitis was defined as GS&gt;1 and/or PD&gt;0, while flare was captured by DAS44 ≥2.4 or SJC&gt;1. <h3>Results</h3> Three out of 67 patient (4%) experienced a flare while continuing their combination of synthetic and biological treatment. These 3 patients showed subclinical synovitis in at least one joint at the US examination. Another 36 patients were also positive on US, but did not experience a flare. The 28 patients that were US negative did not differ from the US positive cases if we compared clinical features such as tender joints, rheumatoid factor or acute phase reactants. ACPA was slightly higher in the US negative group but did not reach statistical significance. <h3>Conclusions</h3> A low flare rate (4%) was observed among patients in remission continuing their combination therapy of synthetic and biological DMARDs for 3 months, while 2/3 of the patients had a least one positive ultrasound joint at baseline. Although the patients who flared were all US positive, using GS&gt;1 and/or PD&gt;0 in at least one joint might not be sufficient to discriminate who will clinically flare. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2012
Abstract P3-02-03: Increased risk of breast cancer in women with false-positive screening test: can it be entirely explained by misclassification?
Authors: M von Euler-Chelpin, M Kuchiki, I Vejborg
Journal: Cancer Research (2012)

Abstract Background: Screening for disease in healthy people inevitably leads to some false-positive tests. A recent study (von Euler-Chelpin et al, JNCI 2012) showed that women with a false-positive test from screening with mammography had an increased risk of being diagnosed with breast cancer later in life as compared to women with only negative results (RR = 1.67, 95% CI 1.45 to 1.88). The reasons for this excess risk remain unknown. In the present study we have assessed misclassification and evaluated the impact of misclassification on over all excess risk. Method: We used data from the population-based screening mammography program in Copenhagen, Denmark, and studied 295 women exposed to a false-positive test that later developed breast cancer. Screening took place between 1991 and 2006, with a follow-up for cancer until 2008. Cancers that developed in the same location as the finding that initially caused the recall were defined as misclassified and excluded in the assessment of the excess risk among the false-positives. Time from diagnosis, breast density, tumor size, receptor and nodal status were also taken into account. Results: 72 cases were found to be misclassified. When the misclassified tests had been excluded, we still found a significant excess risk for breast cancer of 27% (RR = 1.27, 95% CI (1.11 to 1.46) among the women with a false-positive test compared to women with only negative tests. Women with a false-positive test proven at assessment (Type 1) had an excess risk of 27% (RR = 1.27, 95% CI (1.09 to 1.46), while false-positives proven at surgery (Type 2) had an excess risk of 30 % (RR = 1.30, 95% CI (0.86 to 1.96). In the group of women with misclassified tests there were a significantly higher proportion of breasts with fatty tissue (BI-RADS density classification 1 or 2) than among the non-misclassified. The average time from first false-positive test to time of diagnosis was significantly shorter among women with misclassified tests, 4.0 years versus 7.8 years (p &amp;lt; .0001). There were no significant differences in tumor size, receptor or nodal status. Conclusion: The results indicate that the increased risk can not be explained only by misclassification. The excess risk remains for both Type1 and Type 2 false-positives, which favors some biological susceptibility, as women with false-positive test Type 2 have undergone surgery, which thus makes residual misclassification unlikely. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-03.
Effect of Very Low Birth Weight and Subnormal Head Size on Cognitive Abilities at School Age
Authors: Maureen Hack, Naomi Breslau, Barbara Weissman, Dorothy Aram, Nancy Klein, Elaine Borawski
Journal: New England Journal of Medicine (1991)

We tested the hypothesis that very-low-birth-weight (less than 1.5 kg) infants with perinatal growth failure whose head size is not normal by eight months of age (corrected for prematurity) have significantly poorer growth and neurocognitive abilities at school age than very-low-birth-weight children with a normal head size at eight months. We also hypothesized that these differences would persist even after control for major neurologic impairment and perinatal and sociodemographic risk factors.We have followed a cohort of very-low-birth-weight children since their birth during the period 1977 to 1979. At eight to nine years of age 249 children were evaluated with a neurologic examination and tests of intelligence; receptive and expressive language skills; speech, reading, mathematics, and spelling aptitude; visual and fine motor abilities; and behavior. Ages were corrected for premature birth.Among these 249 very-low-birth-weight children, head size was subnormal (less than the mean -2 SD for age) at birth in 30 (12 percent), at term in 57 (23 percent), and at eight months in 33 (13 percent). As compared with the 216 children with normal head sizes, the 33 children with subnormal head sizes at the age of eight months had significantly lower mean birth weights (1.1 vs. 1.2 kg) and higher neonatal risk scores (71 vs. 53) and at the age of eight years had a higher incidence of neurologic impairment (21 percent vs. 8 percent) and lower IQ scores (mean verbal, 84 vs. 98). Even among the children without neurologic abnormalities, a subnormal head size at eight months of age was predictive of poorer verbal and performance IQ scores at eight years of age; lower scores for receptive language, speech, reading, mathematics, and spelling; and a higher incidence of hyperactivity. In multiple regression analyses to control for socioeconomic and neonatal risk factors, intrauterine growth failure, birth weight, and neurologic impairment, a subnormal head size at eight months of age had an independently adverse effect on IQ and on scores for receptive language, speech, reading, and spelling.In very-low-birth-weight infants, perinatal growth failure, as evidenced by a subnormal head circumference at eight months of age, is associated with poor cognitive function, academic achievement, and behavior at eight years of age.
Care of the Hopelessly Ill
Authors: T E Quill, C K Cassel, D E Meier
Journal: New England Journal of Medicine (1992)

One of medicine's most important purposes is to allow hopelessly ill persons to die with as much comfort, control, and dignity as possible. The philosophy and techniques of comfort care provide a humane alternative to more traditional, curative medical approaches in helping patients achieve this end.1 2 3 4 5 6 Yet there remain instances in which incurably ill patients suffer intolerably before death despite comprehensive efforts to provide comfort. Some of these patients would rather die than continue to live under the conditions imposed by their illness, and a few request assistance from their physicians.The patients who ask us to face such predicaments . . .
Racial disparities in breast cancer knowledge.
Authors: GA Petrak
Journal: Cancer Research (2009)

Abstract Abstract #5099 Background: Many women fear breast cancer, but may know a great deal about the disease. We assessed the breast cancer attitudes and knowledge of women who self-identified as Caucasian, African American, Asian American, and Hispanic/Other.&amp;#x2028; Methods: We created a survey to measure women's attitudes and knowledge regarding breast cancer. We surveyed women outside retail establishments in Michigan and Washington, DC. We obtained 160 responses. We analyzed the data using the students t-test for continuous variables and the chi-square test for categorical variables, with significance set at the 0.05 level.&amp;#x2028; Results: The racal distribution was: Caucasian, N = 119 (74.4%); African American, N = 19 (12%); Asian American, N = 17 (11%); other, 4 (2.5%), one respondant did not state her race. We asked: (1) Have you ever had a mammogram? Caucasian, No = 38 (32%); African American, No = 6 (33%); Asian American, No = 13 (76%): P=0.007. (2) True/False: A mammogram does not use radiation to image the breast. Caucasian, False = 72 (64%); African American, False = 13 (76%); Asian American, False = 9 (56%): P = 0.07. (3) True/False: All women with breast cancer need chemotherapy. Caucasian, False = 88 (93%); African American, False = 11 (92%); Asian American, False = 10 (77%): P = 0.03. (4) True/False: All women who need chemotherapy receive it. Caucasian, False = 88 (93%); African American, False = 11 (92%); Asian American, False = 10 (77%): P = 0.04.&amp;#x2028; Discussion: Caucasians and African Americans were very similar in their breast cancer knowledge, but Asian Americans were less likely to have had a mammogram, less likely to know about radiation and mammograms, less likely to believe that all women with breast cancer need chemotherapy, and more skeptical regarding whether women who need chemotherapy actually receive it. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5099.
The Ewing Family of Tumors -- A Subgroup of Small-Round-Cell Tumors Defined by Specific Chimeric Transcripts
Authors: Olivier Delattre, Jessica Zucman, Thomas Melot, Xavier Sastre Garau, Jean-Michel Zucker, Gilbert M. Lenoir, Peter F. Ambros, Denise Sheer, Claude Turc-Carel, Timothy J. Triche, Alain Aurias, Gilles Thomas
Journal: New England Journal of Medicine (1994)

Precise diagnosis of small-round-cell tumors is often a challenge to the pathologist and the clinical oncologist. In Ewing's sarcomas and related peripheral primitive neuroectodermal tumors, a t(11;22) translocation or a (21,22) rearrangement is associated with hybrid transcripts of the EWS gene with the FLI1 or ERG gene. To investigate the diagnostic implication of this observation, we searched for these hybrid transcripts in tumors from patients with clinical and radiologic features of Ewing's sarcoma or peripheral primitive neuroectodermal tumors.Samples of RNA from 114 tumors were reverse transcribed and subjected to the polymerase chain reaction with primers designed to amplify the relevant chimeric transcripts. All amplified products were sequenced.In-frame hybrid transcripts were observed in 89 cases. A hybrid transcript was found in 83 of 87 cases (95 percent) of Ewing's sarcoma or peripheral primitive neuroectodermal tumors. Samples of RNA from all of 12 tumors that had been proved to be other than Ewing's sarcoma or neuroectodermal tumors had no hybrid transcript. However, 6 of 15 undifferentiated tumors whose type was ambiguous (nonsecreting, poorly differentiated neuroblastoma or undifferentiated sarcoma) contained a hybrid transcript, suggesting that they might have to be reclassified.A subgroup of small-round-cell tumors identified as belonging to the Ewing family of tumors can be defined according to a specific molecular genetic lesion that is detectable by a rapid, reliable, and efficient method. This approach can be applied to small specimens obtained by fine-needle biopsies.
AB0146 Ursolic Acid Ameliorates Autoimmune Arthritis via Suppression of TH17 and B Cell Differentiation
Authors: S.-K. Kwok, J. Lee, J.H. Koh, H.K. Min, J.Y. Kang, Y.S. Suh, J.-H. Lee, S.-M. Jung, J.Y. Lee, J.-M. Kim, J.H. Ju, K.-S. Park, H.-Y. Kim, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ursolic acid (UA) is a pentacytclic triterpenoid compound which is ubiquitously present in plants. <h3>Objectives</h3> Based on its known anti-inflammatory and anti-oxidative effect, this study was undertaken to investigate the effect of UA on collagen-induced arthritis (CIA) and to delineate the underlying mechanism. <h3>Methods</h3> UA (150mg/kg) or 10% dimethyl sulfoxide was injected intraperitoneally three times a week to mice with CIA from the day 14 after immunization. The expressions of proinflammatory cytokines and molecules associated with oxidative stress in arthritic joints were measured by immunohistochemical staining. The number of CD4+IL-17+ cells or CD4+CD25+Foxp3+ cells or phosphorylated (p) STAT3 + cells was determined by confocal immunostaining of the spleen or flow cytometry analysis of splenocytes. The level of mRNA expression and immunoglobulin was analyzed by real time RT-PCR and ELISA, respectively. <h3>Results</h3> UA injection prevented clinical arthritis incidence and joint inflammation in mice with CIA. A significant reduction in pSTAT3 and resultant decrease in the number of Th17 was observed with UA treatment. Consistently, the expression of IL-17 and retinoic acid orphan receptor (ROR)γt was markedly reduced with UA. Although the expression of Foxp3 was unaffected, the number of Treg cells was increased with UA treatment. There was a marked reduction in type II collagen-specific immunoglobulin G production. When IL-21-or LPS-stimulated CD19+ B cells were cultured in the presence or absence of UA, the mRNA expression of markers associated with B cell activation (Bcl-6), plasma cell differentiation (Blimp-1) and isotype switching (activation-induced deaminase) was markedly reduced with UA treatment. <h3>Conclusions</h3> Our findings suggest that UA can regulate Th17 and reciprocally promote Treg cells by inhibiting expression of ROR γt and pSTAT3. UA also inhibits plasma cell differentiation, resulting in a reduction of immunoglobulin production. By targeting pathogenic Th17 and immunoglobulin production, UA may be a novel therapeutic for treatment of autoimmune arthritis and other Th17-related diseases. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3181