tbuckley/cabot-search huggingface dataset:
Abstract 555: Gene expression differences in primary breast tumors from African American and Caucasian women.
Authors: Lori A Field, Brad Love, Brenda Deyarmin, Jennifer Kane, Jeffrey A Hooke, Rachel E Ellsworth, Craig D Shriver
Journal: Cancer Research (2008)

Abstract Background: Incidence of breast cancer varies across ethnic groups. Overall incidence is highest among Caucasian women (CW); however, incidence in women younger than 40 as well as mortality is highest among African American women (AAW). Although socioeconomic disparities are often blamed for these differences, AAW are more likely than CW to present with large, aggressive tumors with poor prognostic features such as estrogen receptor negativity, triple negative phenotype, and lymph node involvement, suggesting that molecular factors may also contribute to the younger age of onset and worse outcomes in AAW. In the present study, we have compared primary breast tumors from AAW and CW by gene expression profiling to identify differentially expressed genes that may explain why diagnosis at a young age, aggressive tumor biology and lower survival are more prevalent in AAW than CW with breast cancer. Materials and Methods: Breast tumor specimens were obtained from 26 pairs of age and stage-matched AAW and CW enrolled in the Clinical Breast Care Project (CBCP). Tumor cells were isolated by laser microdissection (Leica) and RNA isolated using the RNAqueous Micro kit (Ambion). RNA was amplified and labeled with biotin-11-UTP using two rounds of amplification with the MessageAmp II aRNA Amplification kit (Ambion). Fragmented aRNA was hybridized to the HG U133A 2.0 array (Affymetrix). A Mann-Whitney U test was used to identify differentially expressed genes (p ≤ 0.001). Results: Sixty-five genes were differentially expressed between AAW and CW. Twenty-eight genes were more highly expressed in AAW, including SOS1, TSPO, and PSPH, while 37genes had lower expression in AAW, including ZNF228, SCAMP4, and PSD3. Discussion: These results support a model in which molecular factors influence breast cancer onset, progression and prognosis in AAW. Genes with higher expression in tumors from AAW function in steroid, fatty acid, and serine biosynthesis, signal transduction, cell proliferation and adhesion, and cytoskeleton organization and biogenesis. Functions of genes with lower expression in AAW tumors include regulation of transcription, vesicular transport, iron metabolism, signal transduction, and extracellular matrix organization and biogenesis. These results suggest that breast tumors from AAW and CW differ at the gene expression level and that these differences may be responsible for the more aggressive clinical features of breast tumors in AAW compared to CW.
THU0630 Immune-related adverse events associated with immune checkpoint inhibitors in spanish patients
Authors: L. Villalobos, W.A. Giraldo-sifuentes, P. Moran-alvarez, J. Arroyo palomo, A. Briones-figueroa, C. Rita, J.L. Morell-hita
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immune checkpoint inhibitors (ICI), a type of immunotherapy which block negative co-stimulation of T-cells, have surfaced as an important alternative of treatment for advanced malignancies. Unfortunately, these agents have been associated with immune-related adverse events (irAE). <h3>Objectives</h3> To analyse the frequency, type and outcome of irAE in Spanish patients treated with ICI. <h3>Methods</h3> We carried out a retrospective, observational and longitudinal study, including adult patients diagnosed with cancer and treated with ICI followed in our centre (Spanish university hospital) from October 2012 to December 2017. Demographics, clinical, therapeutic and outcome date were collected from their medical records. <h3>Results</h3> We included 125 patients, 66.4% males, all them Caucasians, with a mean age at diagnosis 63 years (range:42–81). The most common types of cancers were lung carcinoma (61.6%) and melanoma (12.8%). The ICI most frequently used was nivolumab (29.6%), followed by pembrolizumab (8.8%) and atezolizumab (8.8%), as monotherapy. It was also common, combinations, or the use of consecutive way with different drugs. Occurrence of irAE was reported in 51 patients (table 1) and the systems more frequently involved were gastrointestinal tract, endocrine glands and skin. Most of these cases were treated steroids at high doses but a case of colitis required infliximab. Withdrawal of immunotherapy was required in almost half of the adverse events (45%). During the follow-up period there were 5 deaths associated with irAE. <h3>Conclusions</h3> The frequency and type of irAE associated ICI in our series were similar to those reported in previous studies, except for rheumatological events, being arthritis and sicca syndrome the most frequently reported in other series. These adverse events are not rare and may be a potential cause of morbity in these patients, so it is important to recognise them early and treat properly, with the rheumatologist being one of the specialists involved. <h3>Disclosure of Interest</h3> None declared
Rps14, Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q- syndrome
Authors: Flavia Ribezzo, Inge A. M. Snoeren, Susanne Ziegler, Jacques Stoelben, Patricia A. Olofsen, Almira Henic, Monica Ventura Ferreira, Si Chen, Ursula S. A. Stalmann, Guntram Buesche, Remco M. Hoogenboezem, Rafael Kramann, Uwe Platzbecker, Marc H. G. P. Raaijmakers, Benjamin L. Ebert, Rebekka K. Schneider
Journal: Leukemia (2019)
AB0628 Infections in hospitalised patients with systemic lupus erythematosus- a prospective observational study from a tertiary care centre in southern india
Authors: S. Alur, M.M. Thabah, V.S. Negi, S. Sistla
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Infections are one of the main causes of morbidity and mortality in SLE.<sup>1</sup> The high prevalence of infection is attributed to use of immunosuppressive agents and disease activity. There is paucity of literature from India on infections, types of infections, predictors and outcome. <h3>Objectives</h3> To determine the frequency, types and determinants of major infections in hospitalised patients with SLE. <h3>Methods</h3> Patients with SLE (2012 SLICC-ACR criteria) aged ≥13 years, admitted to Clinical Immunology and Medicine wards were included. Clinical evaluation for major organ involvement of SLE, disease activity was assessed by SLEDAI-2K. Whenever there was a suspicion of infection appropriate work up to find the etiology of infections was done. Major infection was defined as presence of either one of the following a) sepsis b) pneumonia, or pyelonephritis, or endocarditis, or meningitis. c) skin or soft tissue infection requiring hospital admission for treatment d) Infection requiring IV antibiotic therapy. The diagnosis of infection was made by compatible clinical, microbiological and imaging criteria. <h3>Results</h3> From December 2016 till January 2018, 63 (55 women and 8 men) were included; Mean age was 28.8±9.8 years; mean SLEDAI-2K was 14.6±7.03. Median duration of hospital stay was 14 days; range 2–64 days. Disease manifestation (including present and ever present) were arthralgia/arthritis in 51 (81%), oral ulcers 56 (88.9%), myositis 10 (15.9%), lupus nephritis 35 (55.6%), CNS lupus 14 (22.2%), serositis 14 (22.2%), cardiac involvement 13 (20.6%), APS 3 (4.8%). At the time of enrollment thrombocytopenia was present in 13 (20.6%), and leukopenia 11 (17.5%). Twenty-three of 63 (36.5%) had infections (table 1), 14/23 (60.8) were microbiologically proven, remaining (39.2%) were confrrmed by compatible clinical features and imaging. Seven of 63 (11.1%) died; 5 (21.7%) in the infection group versus 2 (5%) in no infection group, p=0.08 OR 5.58 [CI 0.98–31.7]. Thirty-four of 63 (54%) had fever on admission; 17/23 (74%) patients with infection had fever compared to 17/40 (42.5%) in no infection group, p=0.02 [OR=3.8, CI 1.2–11.7]. There was no association of lupus nephritis, CNS lupus, leukopenia, receipt of cyclophosphamide, rituximab, methylprednisolone pulse therapy with occurrence of infection. <h3>Conclusions</h3> Almost 36% of SLE patients in hospital have infections. There appeared to be an increase in number of deaths among patients with infections. There was no association of infections with the dose of prednisolone or previous immunosuppression with cyclophosphamide. <h3>Reference</h3> [1] Shyam C, Malaviya AN. Infection-related morbidity in systemic lupus erythematosus: a clinico-epidemiological study from northern India. Rheumatol Int. 1996; 16: 1–3. <h3>Disclosure of Interest</h3> None declared
Timeline and location of recurrence following successful ablation in Barrett’s oesophagus: an international multicentre study
Authors: Sarmed S Sami, Adharsh Ravindran, Allon Kahn, Diana Snyder, Jose Santiago, Jacobo Ortiz-Fernandez-Sordo, Wei Keith Tan, Ross A Dierkhising, Julia E Crook, Michael G Heckman, Michele L Johnson, Ramona Lansing, Krish Ragunath, Massimiliano di Pietro, Herbert Wolfsen, Francisco Ramirez, David Fleischer, Kenneth K Wang, Cadman L Leggett, David A Katzka, Prasad G Iyer
Journal: Gut (2019)

Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett's oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines.Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies.594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4-4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI -7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia).BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.
THU0670 A reumatologist’s evaluation of how efficiencies in the management of painful lumbar syndrome in work disability creates benefits &amp; savings
Authors: V.M. Flores Rodríguez, F. Díaz Gonzalez, S. Bustabad Reyes, M. Carballo Correa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Musculoskeletal disorders are the most important cause of sick leave in the world.<sup>1</sup> Lumbar pain is the main cause of temporary incapacity whith significant socio-economic impact. <h3>Objectives</h3> Test efficiency of Healthcare approach by rheumatologist as savings in indirect costs e.g days off work and in direct costs derived from medical assistance in controlled patient group on sick leave diagnosed with lumbar pain. <h3>Methods</h3> 2 year quasi-experimental bi-directional analytical design trial. Retrospective cohort in Control Group- CG and prospective cohort for intervention group -IG. Two groups, IG and CG respectively contain 150 (56% women aged 47.5 years±10) and 172 (48.8% women aged 44.2 years±10) working age patients with lumbar pain. Study made by Program for the Management of Temporary Disability implemented by Rheumatology Service of University Hospital of the Canary Islands. Study included early intervention, protocol in diagnostic tests and treatment. This study was evaluated by the Ethics Committee of the research of the University Hospital of Canary Islands fulfilling the requirements of suitability. <h3>Results</h3> 24% of patients of IG fit to return to work after first appointment. Maximum efficiency of study between 30thand 45th day of sick leave. At 45 days 8% IG and 18,6% CG remained on sick leave. Average reduction 26 days of sick leave respect to CG, a total saving of 6.182 days of sick leave over 1 year, with efficiency of 62,2%. Saving in direct costs in IG over CG: medicaments, complementary tests, inter-consultations, follow up 48%. Absolute saving of 38.891€, or equivalent 256.680€ for 1.000 patients. National Institute of Social Security Indirect sick leave costs 67,1%. Absolute saving of 129.883€, or equivalent of 857.227€ for 1.000 patients. Indirect costs savings for Employers for intervention 50%. Absolute saving 108.649€, or equivalent to 717.083€ for 1.000 patients. Workers in program saved 50% in salary loss. Average saving 605€/worker. Total saved by implementation of program to State, to worker, to Employer-360.142€. Program Cost effective, producing average annual saving per patient of 259€ and average reduction of sick leave days of 41,2. Program cost efficiencies produced. Every day of disability saved equivalent to implementation cost of 5,06€. Cost-benefit program produced for State saving of 6,44€ for every € invested in implementation 137.248€. Program had 93,8% patient acceptance expressing maximum satisfaction. <h3>Conclusions</h3> Management of disability by rheumatologist highly profitable given low program implementation cost compared to savings generated for State and Employer. <h3>Reference</h3> [1] WHO.The burden of musculoskeletal conditions at the star of the millenium. En: WHO Technical Report Series: 919.Geneva 2003. <h3>Disclosure of Interest</h3> None declared
CAF-Derived IL6 and GM-CSF Cooperate to Induce M2-like TAMs–Letter
Authors: Vittoria Iorio, Margot De Marco, Anna Basile, Daniela Eletto, Mario Capunzo, Paolo Remondelli, Gianluca Sala, Liberato Marzullo, Alessandra Rosati, Vincenzo De Laurenzi, Maria C. Turco
Journal: Clinical Cancer Research (2019)

In a recent article, Cho and colleagues highlight the connection between cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) in tumor progression. They show that cancer cell–activated CAFs induced monocyte differentiation into M2-like TAMs via IL6 and GM-CSF release, and
AB0130 Serum leptin and adiponectin levels in rheumatoid arthritis patients, their association with inflammatory process
Authors: O. Galiutina, S. Shevchuk, Y. Seheda, I. Kuvikova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is well known that such bioactive substances as leptin and adiponectin are involved in different pathologic process including inflammation. At the same time, in a number of studies it was demonstrated anti-flammatory properties of adipokines. Many studies have shown increasing leptin level and reducing adiponectin level in patients with rheumatoid arthritis (RA) compared with healthy ones. On the other hand the roles of adipokines in pathogenesis of autoimmune disorders are still controversial due to their both pro-inflammatory and anti-inflammatory effects. <h3>Objectives</h3> The aim of this study was to evaluate adipokine levels in patients with RA and to assess their association with the activity of inflammatory process <h3>Methods</h3> The study included 62 patients with RA and 35 practically healthy sex and age matched persons of control group. The diagnosis of RA was established according to the ACR 2010. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were used to assess inflammation. Disease activity and functional impairment were evaluated using the Disease Activity Score (DAS28). Serum leptin and adiponectin levels were studied by immunoassay using standard sets (DRG", Germany and "Orgenium", Finland). Results are expressed as mean ±standard error of the mean. Spearman's r was used to calculate correlations between markers of disease activity (ESR, CRP, DAS28) and serum adipokine levels. A p value&lt;0.05 was considered statistically significant for all tests <h3>Results</h3> It was found that the mean value of leptin and adiponectin levels were 20.7±12.3 ng/ml and 2.47±1.34 ng/ml respectively in patients with RA and 6.47±3.17 ng/ml and 4.21±1.4 ng/ml respectively in the control group. Thus, the leptin level in patients with RA was 3.2 times higher, and adiponectin level was 1.7 times lower than in healthy individuals. Levels of adipokins were associated with the activity of the inflammatory process. Thus, serum concentration of leptin level was increased (r=0.33 and r=0.35) and adiponectin level was decreased (r=−0.25 and r=−0.24) with the increasing of ESR and CRP. Similar patterns were observed for the integral index of RA activity DAS28. In particular, DAS28 was 1.6 times higher in subjects with leptin levels above 44.7±9.4 ng/ml than in the group of patients with leptin levels below 44.7±9.4 ng/ml. The correlation analysis has also confirmed the close association between the leptin and adiponectin levels with DAS28 activity index (r=0.37 and r=−0.28, respectively). <h3>Conclusions</h3> Disadipokineemia in patients with RA is characterised by the increasing of serum leptin level and the decreasing of serum adiponectin level and is closely related to the activity of the inflammatory process. <h3>Disclosure of Interest</h3> None declared
THU0097 Phosphodiesterases 4 (PDE4) inhibitor ameliorates experimental arthritis
Authors: W. Chen, Z. Xu, H. Wee, G.S. Lewis, N. Olsen, J. Lin, S.G. Zheng
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory bone-destructive disorder with autoimmune features. Apremilast is a novel phosphodiesterases 4 (PDE4) inhibitor suppressing immune and inflammatory responses. <h3>Objectives</h3> We assessed the anti-inflammatory and bone protection effects of apremilast in collagen CII induced arthritis (CIA)models. <h3>Methods</h3> Apremilast was given starting from day 14 after immunisation, we investigated whether apremilast (5 mg/kg or 25 mg/kg) can ameliorate arthritis onset. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti–mouse type II collagen (CII) antibody levels were measured by enzyme-linked immunosorbent assay. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency (SCID) mouse model of RA were used to study the role of apremilast in suppression of RASFs destroying cartilage <i>in vivo</i>. <h3>Results</h3> We found that apremilast therapy delayed arthritis onset and reduced arthritis scores in CIA model at a different dose, compared to CIA model and blank vector (figure 1A). Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in apremilast groups. Furthermore, apremilast can prevent CIA mice from bone erosion by CT analysis. High dose of apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA (figure 1B, C). Apremilast treatment can inhibit destroy and migratory ability of RASFs to cartilages. Compared to the model group, Apremilast treatment significantly reduced the invasion scores in both primary implant and contralateral implant. <h3>Conclusions</h3> Our data suggest that apremilast was effective in preventing arthritis and bone erosion in CIA model, implicating a potential promise of therapy on rheumatoid arthritis. <h3>Acknowledgements</h3> This work is supported in part by the grants from the Celgene Foundation, NIH R01 059103, National Natural Science Foundation of China (81671611, 81701600). <h3>Disclosure of Interest</h3> None declared
AB1337 Celiac disease and risk of sarcoidosis: a systematic review and meta-analysis
Authors: K. Wijarnpreecha, P. Panjawatanan, P. Lertjitbanjong, J.E. Corral, P. Ungprasert
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Several epidemiologic studies have demonstrated that patients with celiac disease may be at an increased risk of devleoping sarcoidosis. However, the data on this risk remain inconsistent. <h3>Objectives</h3> To compare the risk of developing sarcoidosis between patients with celiac disease and individuals without celiac disease. <h3>Methods</h3> A literature review was performed using MEDLINE and EMBASE database from inception to December 2017. Studies that compared the risk of sarcoidosis among patients with celiac disease versus those without celiac disease were included. The inclusion criteria were as follows:<sup>1</sup> case-control, cross-sectional or cohort studies that investigated the risk of sarcoidosis among patients with celiac disease compared with individuals without celiac disease and<sup>2</sup> odds ratios (OR), relative risks (RR), hazard ratios (HR) or standardised incidence ratios (SIR) with 95% confidence intervals (CI) or sufficient raw data to calculate these ratios were provided. Study eligibility was independently determined by 3 investigators. Differences in the determination of study eligibility were resolved by mutual consensus. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. <h3>Results</h3> Of 375 retrieved studies, 4 studies (2 case-control studies and 2 cohort studies) with 6 93 639 participants met our eligibility criteria and were included in analysis. We found a higher risk of sarcoidosis among patients with celiac disease compared with individuals without celiac disease with the pooled OR of 7.16 (95% CI, 1.48–34.56). The statistical heterogeneity of this study was high (I<sup>2=</sup>95%). Funnel plot was relatively symmetric and did not suggest the presence of publication bias in favour of positive studies. <h3>Conclusions</h3> This systematic review and meta-analysis found a significantly higher risk of sarcoidosis among patients with celiac disease. <h3>Disclosure of Interest</h3> None declared