tbuckley/cabot-search huggingface dataset:
Genome sequencing of children promises a new era in oncology
Authors: Jacqui Wise
Journal: BMJ (2019)

All children with cancer in England will be offered whole genome sequencing from this year in a move that will enable more comprehensive and precise diagnosis and access to more personalised treatments.

NHS England’s long term plan says that this will reduce the use of harmful drugs and interventions, support increased access to clinical trials, and reduce the number of young patients who have health problems caused by chemotherapy and radiotherapy.12

The smaller numbers—there are around 1800 paediatric cancers diagnosed a year—means it is more feasible to offer whole genome sequencing to all children rather than all adults with cancer. However, adults with certain rare conditions or specific cancers will also be offered full genome screening. NHS England says by 2029 over 100 000 people a year can access these tests.

Aine McCarthy, from Cancer Research UK’s children’s cancers team, said that the announcement was very exciting. “It will give us a load of new …
SP0086 The development and purpose of the eular recommendations for physical activity in people with inflammatory arthritis and osteoarthritis
Authors: K. Niedermann
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objective</h3> Regular physical activity (PA) is increasingly promoted for people with rheumatic and musculoskeletal diseases as well as the general population. We evaluated if the public health recommendations for PA are applicable for people with inflammatory arthritis (iA; Rheumatoid Arthritis and Spondyloarthritis) and osteoarthritis (OA) in order to develop evidence-based recommendations for advice and guidance on PA in clinical practice. <h3>Methods</h3> The EULAR standardised operating procedures for the development of recommendations were followed. A task force (including rheumatologists, other medical specialists and physicians, health professionals, patients and methodologists) from 16 countries met twice. In the first task force meeting, 13 research questions to support a systematic literature review (SLR) were identified and defined. In the second meeting, the SLR evidence was presented and discussed before the recommendations, research agenda and education agenda were formulated. <h3>Results</h3> The task force developed and agreed on four overarching principles and ten recommendations for PA in people with iA and OA. The mean level of agreement between the task force members ranged between 9.8 to 8.8. Given the evidence for its effectiveness, feasibility and safety, PA is advocated as an integral part of standard care throughout the course of these diseases. Finally, the task force agreed on a related research and education agenda. <h3>Conclusion</h3> Evidence and expert opinion inform these recommendations to provide guidance in the development, conduct and evaluation of PA interventions and promotion in patients with iA and OA. It is advised that these recommendations should be implemented considering individual needs and national health systems. <h3>Disclosure of Interest</h3> None declared
Abstract 18868: Ethnic and Gender Differences in the Occurrence and Outcomes in Patients With Diabetes: Results of the Platinum Diversity Study
Authors: Wayne Batchelor, Kevin Boran, Henry Liberman, George Kichura, Paul Mullen, Ali Mortazavi, Mark Grabarczyk, George Mark Jenkins, Paul Underwood, Craig Thompson, Roxana Mehran
Journal: Circulation (2017)

Introduction: Approximately 25% of patients who undergo percutaneous coronary intervention (PCI) have diabetes which nearly doubles the mortality risk. The prevalence of diabetes varies among diffe...
THU0606 Effect of interleukin-1 antagonists on the quality of life in familial mediterranean fever patients
Authors: Ö. Varan, H. Küçük, H. Babao&gbreve;lu, N. Atas, H. Satıs, R. Bilici Salman, A. Tufan, B. Göker, S. Haznedaro&gbreve;lu, M.A. Öztürk
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is characterised by febrile inflammatory painful attacks of peritonitis, pleuritis, arthritis and erzypeloid erythema. Colchicine is the mainstay of treatment in FMF but about%10 patients do not respond well to colchicine. IL-1 antagonists have been shown to be effective in the prevention of attacks in colchicine resistant FMF (crFMF) patients. Herein we investigated effect of these agents on quality of life of crFMF patients. <h3>Objectives</h3> to investigate effect of IL-1 antagonists on quality of life of crFMF patients. <h3>Methods</h3> Data is derived from Gazi FMF cohort which was established in year 2010. Since then data of patients with FMF who were diagnosed according to the Tel Hashomer criteria were registered. Co-morbidities, detailed attack characteristics, treatments, laboratory parameters and impact of FMF on their life in terms of quality of life were recorded. A retrospective cohort analysis was made from records of patients who were treated with IL-1 inhibitors. SF-36 form was filled before and 3 months after the IL-1 antagonist treatment. Wilcoxon test was used for the analyses and a p value equal or less than 0.05 is considered as statistically significant. <h3>Results</h3> there were 41 patients (24 women and 17 men). Anakinra was used in 33 patients and 8 patients received canakimumab. There was a statistically significant reduction in the frequency, severity and the duration of attacks after treatment with IL-1 antagonists (p&lt;0.001, for each). A statistically significant improvement was observed in all domains of SF-36 (figure 1). <h3>Conclusions</h3> IL-1 inhibitor therapy reduces frequency, severity and duration of attacks and significantly improves the quality of life of crFMF patients. <h3>Disclosure of Interest</h3> None declared
AB0894 A comparison of clinical features in patients with spondyloarthritis and unilateral or bilateral hip arthritis
Authors: W. Hamdi, S. Zrida, H. Riahi, K. Maatallah, D. Kaffel, M. Chelli Bouaziz, M.F. Ladeb, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Axial spondyloarthritis (AS) is a frequent chronic and progressive disease that affects mainly young adults and is characterised by inflammation of the axial skeleton, but peripheral joints such as hips may also be involved. The incidence of hip involvement in AS is around 30%.<sup>1</sup> Nevertheless, data concerning clinical features in patients with spondyloarthritis comparing unilateral and bilateral hip arthritis are lacking. <h3>Objectives</h3> To compare clinical, functional and radiologic outcomes in patients with AS with unilateral or bilateral hip arthritis. <h3>Methods</h3> Cross-sectional study on 100 patients with AS according to the <sup>ASAS criteria of 2009</sup> who had unilateral and bilateral hip joint lesions defined by hip pain, limited joint motion and radiographic hip abnormalities. Demographic and clinical outcomes were performed including HLA B27 status. Spinal mobility outcomes were assessed by Schöber index and Bath Ankylosing Spondylitis Metrology Index (<i>BASMI</i>). Radiographic measurements were performed and included Bath Ankylosing Spondylitis Radiology Index (<i>BASRI</i>) and modified Stoke Ankylosing Spondylitis Spinal <i>Score</i> (mSASSS). <h3>Results</h3> Bilateral hip joint lesion was reported in 76% of patients which 14 were women and mean age was 37.14 years. Bilateral hip involvement was associated with less height (p=0.002), more long disease duration (p=0.015), more several clinical spinal involvements with more spinal stiffness (p=0.000) and less spinal mobility (p=0.004). Extra-articular manifestations were comparable in patients with unilateral and bilateral hip arthritis (p=0.55), however HLA B27 antigen was significantly more common (p=0.003) in patients with bilateral hip arthritis. BASRI hip (p=0.042) and mSASSS (p=0.009) scores were used to asses structural damage on plain radiographs and were significantly more important in bilateral involvement. Nevertheless, protrusive form was more frequent in patient with unilateral hip involvement (p=0.05). <h3>Conclusions</h3> Bilateral hip arthritis seems to be more frequent and more severe than unilateral involvement in patients with AS. <h3>Reference</h3> [1] A. Calin, J. Elswood. <b>The relationship between pelvic, spinal and hip involvement in ankylosing spondylitis: one disease process or several?</b>Br J Rheumatol, 27 (1988), pp. 393–395 <h3>Disclosure of Interest</h3> None declared
A phase II study of a yeast-based therapeutic cancer vaccine, GI-6207, targeting CEA in patients with minimally symptomatic, metastatic medullary thyroid cancer.
Authors: Ravi Amrit Madan, Nishith K. Singh, Ann Wild Gramza, Antonio Tito Fojo, Christopher Ryan Heery, Joseph W. Kim, Sheri McMahon, Myrna Rauckhorst, Thomas H King, David Apelian, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2013)

TPS3127 Background: Saccharomyces cerevisiae has been genetically modified to express CEA protein and developed under a CRADA with GlobeImmune/NCI as a heat-killed immune-stimulating, therapeutic cancer vaccine (GI-6207). A phase I study with GI-6207 demonstrated safety, biomarker stabilization and enhanced immune response in some patients. CEA is over-expressed in multiple malignancies, including medullary thyroid cancer (MTC). Two therapies recently approved by the FDA for metastatic MTC (vandetanib, cabozantinib) come with toxicity and should be reserved for symptomatic/progressive disease. However, a large population of asymptomatic MTC patients has small tumor burden and/or disease that is more indolent. The standard management of these patients is observation. Preliminary data suggest that tumor growth measured by the rate of CEA and calcitonin increase can be quantified in a 3-6 months. Retrospective data from prostate cancer studies suggest vaccines can alter growth rates within 3-4 months. We hypothesize that GI-6207 can alter tumor growth rates in MTC and impact long-term outcome. Methods: A phase II study will evaluate the effect of GI-6207 onthe rates ofincrease in calcitonin in metastatic MTC. 34 patients with minimally symptomatic, radiographically evaluable, metastatic MTC will be randomized 1:1. Arm A will receive vaccine for a year from the time of enrollment. Arm B will receive vaccine after 6 months of surveillance. GI-6207 will be administered subcutaneously at 4 sites (10 yeast units/site), every 2 weeks for 3 months, then monthly up to 1 year. The primary endpoint will compare the effect of GI-6207 on calcitonin kinetics between the vaccine and surveillance arms in the first 6 months. Secondary endpoints include immunologic responses (including antigen-specific T cell responses), objective responses, time to progression, and changes in CEA kinetics. If this trial can prospectively demonstrate that vaccines can alter tumor growth rates, and if such changes are associated with clinical outcomes, then changes in tumor growth rates may become a clinical metric to evaluate vaccine efficacy in MTC and other populations.
Pharmacokinetics, metabolism, and routs of excretion of intravenous (14 C)-irofulven in patients with advanced solid tumors
Authors: Keyvan Rezai, Pierre Bourgeois, Ghanem Elias Ghanem, Carmen Kahatt, Dominique de Valeriola
Journal: Clinical Cancer Research (2005)

Irofulven is currently in Phase 2 clinical trials against a wide variety of solid tumors and has demonstrated activity in ovarian, prostate, gastrointestinal, and non–small cell lung cancer. The objectives of this study were to determine its pharmacokinetics and route of excretion and to characterize its metabolites in human plasma and urine samples after a 30-min i.v. infusion at a dose of 0.55 mg/kg in patients with advanced solid tumors. Three patients were administered i.v. 100 Ci of [ 14 C]irofulven over a 30-min infusion on day 1 of cycle 1. Serial blood and plasma samples were drawn at 0 (before irofulven infusion) and up to 144 h after the start of infusion. Urine and fecal samples were collected for up to 144 h after the start of infusion. The mean urinary and fecal excretion of radioactivity up to 144 h were 71.2 and 2.9%, respectively, indicating renal excretion was the major route of elimination of [ 14 C]irofulven. The Cmax, AUC0-, and terminal half-life values for total radioactivity were 1130 ng-Eq/ml, 24,400 ng-Eq h/ml, and 116.5 h, respectively, and the corresponding values for irofulven were 82.7 ng/ml, 65.5 ng h/ml, and 0.3 h, respectively, suggesting that the total radioactivity in human plasma was a result of the metabolites. Twelve metabolites of irofulven were detected in human urine and plasma by electrospray ionization/tandem mass spectrometry. Among these metabolites, the cyclopropane ring-opened metabolite (M2) of irofulven was found, and seven others were proposed as glucuronide and glutathione conjugates.
AB0019 The role of the il2-il21 rs6822844 polymorphism in the predisposition to the erythrocyte sedimentation rate elevation in juvenile idiopathic arthritis
Authors: L.S. Nazarova, K.V. Danilko, V.A. Malievsky, T.V. Viktorova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder in paediatrics.<sup>1</sup> The erythrocyte sedimentation rate (ESR) is one of the key measures of the JIA activity.<sup>2</sup> However, in some patients, even in the active disease period, the ESR is not elevated.<sup>3</sup> <h3>Objectives</h3> The aim of the study was to assess the relationship between the <i>IL2-IL21</i> rs6822844 locus polymorphic variants and a predisposition to the ESR elevation in JIA patients. <h3>Methods</h3> The study included 255 JIA patients from the Republic of Bashkortostan, Russia. The ESR was considered elevated if its value exceeded the upper limit of the normal range two or more times. Genotyping was performed by real-time PCR, statistical analysis – using the two-tailed Fisher exact test (p) and the odds ratio (OR) with a 95% confidence interval (CI). <h3>Results</h3> The girls/boys ratio was 65.88%/34.12%. The ESR elevation in the active disease period was seen in 70.98% of patients. When studying the <i>IL2-IL21</i> rs6822844 polymorphic locus, a marginal significance level was noted for the rarer occurrence of the GT genotype in patients with the elevated ESR (14.92% vs. 25.68%, p=0.049, OR=0.508, 95% CI 0.258–0.985, compared with patients with the normal ESR, respectively). After stratification according to the sex, similar differences in the GT genotype frequencies were seen and even intensified only for female JIA patients (15.38% vs. 31.37%, respectively, p=0.022, OR=0.398, 95% CI 0.180–0.897). In addition, a significant increase in the GG genotype proportion and a tendency towards a decrease in the T allele proportion were observed in girls with the elevated ESR (GG: 83.76% vs. 68.63%, p=0.038, OR=2.358, 95% CI 1.058–5.110; T: 8.55% vs. 15.69%, p=0.057, compared with girls with the normal ESR, respectively). <h3>Conclusions</h3> In the present study, the association of the <i>IL2-IL21</i> rs6822844 locus polymorphic variants with a predisposition to the ESR elevation in female JIA patients was shown. <h3>References</h3> [1] Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet2007Mar 3;369(9563):767–78. [2] Giancane G, Consolaro A, Lanni S, Davì S, Schiappapietra B, Ravelli A. Juvenile Idiopathic Arthritis: Diagnosis and Treatment. Rheumatol Ther2016Dec;3(2):187–207. [3] Ramsay ES, Lerman MA. How to use the erythrocyte sedimentation rate in paediatrics. Arch Dis Child Educ Pract Ed. 2015Feb;100(1):30–6. <h3>Disclosure of Interest</h3> None declared
Abstract 19510: Cytochrome C Levels in Post-cardiac Arrest Patients
Authors: Michael N Cocchi, Lars W Andersen, Jon Rittenberger, Benjamin Abella, David Gaieski, Mary Anne Peberdy, Jospeh Ornato, Clifton Callaway, Raul Gazmuri, Michael Donnino, Xiaowen Liu
Journal: Circulation (2015)

Introduction: Cytochrome C is an essential component of the electron transport chain loosely bound to the inner mitochondrial membrane. Plasma Cytochrome C levels have shown to be elevated and associated with mortality in an animal model of cardiac arrest. Hypothesis: We hypothesized that cytochrome C levels would be elevated in post-cardiac arrest patients and higher in non-survivors as compared to survivors. Methods: We enrolled adult, out-of-hospital cardiac arrest patients with return of spontaneous circulation as part of the four-center COMICA study. Blood draws were performed after return of spontaneous circulation. We also performed blood draws in controls without acute illness. We measured plasma cytochrome C levels by applying the human cytochrome C Platinum ELISA (eBioceience, CA) kit to a MSD platform (Meso Scale Discovery, MD) to achieve greater dynamic range and sensitivity. We compared groups using the Wilcoxon Rank-Sum test. We used Spearman’s correlation coefficient (rs) to assess the correlation between Cytochrome C levels and initial lactate levels. Results: A total of 103 post-cardiac arrest patients and 40 controls had Cytochrome C levels measured. Cytochrome C levels were higher in post-cardiac arrest patients as compared to control subjects (2.18 nmol/L [quartiles: 0.74, 7.74] vs 0.20 nmol/L [0.03, 1.12], p &lt; 0.001, Figure 1). Fifty-five (53%) patients in the cardiac arrest group died. Patients who died had higher Cytochrome C levels as compared to survivors (3.66 nmol/L [1.40, 14.8] vs. 1.27 nmol/L [0.16, 2.37], p = 0.001, Figure 2). There was also a significant difference in Cytochrome C levels between patients with a good vs. a poor neurological outcome (1.3 nmol/L [0.3, 3.5] vs. 2.8 nmol/L [0.9, 9.9], p = 0.04). Cytochrome C levels were correlated with initial lactate levels (rs = 0.36, p = 0.001). Conclusion: Cytochrome C levels are elevated in post-cardiac arrest patients and non-survivors has higher levels.
THU0620 On demand use of anakinra for the attacks of familial mediterranean fever (FMF)
Authors: H. Babaoglu, O. Varan, H. Kucuk, N. Atas, H. Satis, R.B. Salman, M.A. Ozturk, B. Goker, S. Haznedaroglu, A. Tufan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> IL-1 blocking agents have been shown to be effective in the prevention of attacks in colchicine-resistant FMF (crFMF) patients by their regular use. However, their high cost, side effects and treatment incompliance limit their use which might be overwhelmed by on-demand use of them which has not been reported in FMF patients. Herein, we evaluated the efficacy of on demand use of anakinra in crFMF patients. <h3>Methods</h3> Data were derived from Gazi FMF cohort which was established in the year 2010. From that date patients with FMF who were diagnosed according to the Tel Hashomer criteria were registered. Co-morbidities, detailed attack characteristics, type, duration, severity, treatments, laboratory parameters and impact of FMF on their life in terms of quality of life and work productivity were recorded either by FMF diary or a mobile phone application (FMF AIDD free to download from AppStore and Android market). A retrospective cohort analysis was made from records of patients who have ever been treated with IL-1 inhibitors. <h3>Results</h3> A total of 60 patients were treated with anakinra in our cohort and 15 patients were identified who were received on demand anakinra protocol. Rationale for on demand use of anakinra was prominent prodrome or trigger for attacks and patients' personal claim. Six patients were switched from regular use and 9 were directly started as on demand use. All were using background colchicine in maximum tolerated doses. None of patients had evidence of persistently elevated acute phase reactants or proteinuria. The median duration of on demand anakinra use was 6 (min 3- max 36) months. Pre- and post- on demand anakinra periods were compared (table 1). Patient reported attack severity (p=0.002), duration (p=0.001), absenteeism (p=0.001) and presenteeism (p=0.002) were significantly improved but C-reactive protein (CRP) remained in the same levels. On demand anakinra prevented progression of prodromes to full-blown attacks which was demonstrated by decrease in the rate of attack/prodrome ratio (p=0.002). On demand anakinra can be continued in 10 subjects on long-term but continuous treatment was required in 5 subjects. Attack frequency and work productivity parameters are adjusted for 3 months intervals. VAS: visual analogue scale, CRP: C-reactive protein, AIDAI: autoinflammatory disease activity index <h3>Conclusions</h3> On demand anakinra significantly improved FMF attacks which suggest this approach would be of benefit in daily practice in selected patients. <h3>Disclosure of Interest</h3> None declared
SP0025 Shared decision making in switching to biosimilars
Authors: T. French
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> This presentation will focus on the speaker's experience of switching patients who are on an originator biologic therapy to a biosimilar, using a shared decision making approach. It will initially explore what constitutes shared decision making, why it is important when switching to biosimilars and the benefits of this approach. The speaker will discuss how this change in therapy was achieved in practice when switching patients to both intravenous and subcutaneous biosimilars. There will be a focus on the patient consultation itself, recognising patient anxiety and an exploration of why some patients declined to switch. The speaker will share how loss of efficacy to the biosimilar was managed, and how this influenced the shared decision making approach. Clinician's concerns will also be considered, specifically the inability to maintain pharmacovigilance (in not having sufficient nursing resources to add patients who had switched to a biosimilar to a national register). This is relevant to shared decision making as providing evidence and reassurance to patients regarding safety of biosimilars relies on this data collection. The guidance referred to in this presentation is from NHS England, National Institute for Health and Care Excellence and the British Society for Rheumatology, so it has a UK focus. However, the main themes of the talk should be relevant to all audience members as it considers the opposing pressures on Rheumatology nurses to be change agents and make cost savings in implementing this switch to biosimilars. Whilst nurses also need to act as the patient advocate in ensuring shared decision making is a reality: that a face-to-face consultation takes place and that the patient can decline to switch and not feel penalised. The speaker will reflect on how the trust in her relationship with her patients was tested by this experience. The main recommendation from this presentation is that rheumatology teams need to be proactive in managing this change and securing extra funding for nursing or pharmacy support. This 'invest to save' approach will enable appropriate consultation with patients to allow them to give informed consent to switch their therapy and feel supported whilst this switch takes place. It also enables maximum cost savings by ensuring the switch occurs quickly. <h3>Disclosure of Interest</h3> None declared
Updated Preliminary Results of a Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib Alone or in Combination with Idelalisib or Entospletinib in Patients with Previously Treated Chronic Lymphocytic Leukemia
Authors: Alexey V Danilov, Charles Herbaux, Martin J.S. Dyer, Peter Hillmen, Simon Rule, Ebenezer A Kio, Xi Huang, Siddhartha Mitra, Lionel Karlin, Christopher Fegan
Journal: Blood (2018)