tbuckley/cabot-search huggingface dataset:
Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma
Authors: Fong Chun Chan, Anja Mottok, Alina S. Gerrie, Maryse Power, Marcel Nijland, Arjan Diepstra, Anke van den Berg, Peter Kamper, Francesco d’Amore, Alexander Lindholm d’Amore, Stephen Hamilton-Dutoit, Kerry J. Savage, Sohrab P. Shah, Joseph M. Connors, Randy D. Gascoyne, David W. Scott, Christian Steidl
Journal: Journal of Clinical Oncology (2017)

Purpose Our aim was to capture the biology of classical Hodgkin lymphoma (cHL) at the time of relapse and discover novel and robust biomarkers that predict outcomes after autologous stem-cell transplantation (ASCT). Materials and Methods We performed digital gene expression profiling on a cohort of 245 formalin-fixed, paraffin-embedded tumor specimens from 174 patients with cHL, including 71 with biopsies taken at both primary diagnosis and relapse, to investigate temporal gene expression differences and associations with post-ASCT outcomes. Relapse biopsies from a training cohort of 65 patients were used to build a gene expression–based prognostic model of post-ASCT outcomes (RHL30), and two independent cohorts were used for validation. Results Gene expression profiling revealed that 24% of patients exhibited poorly correlated expression patterns between their biopsies taken at initial diagnosis and relapse, indicating biologic divergence. Comparative analysis of the prognostic power of gene expression measurements in primary versus relapse specimens demonstrated that the biology captured at the time of relapse contained superior properties for post-ASCT outcome prediction. We developed RHL30, using relapse specimens, which identified a subset of high-risk patients with inferior post-ASCT outcomes in two independent external validation cohorts. The prognostic power of RHL30 was independent of reported clinical prognostic markers (both at initial diagnosis and at relapse) and microenvironmental components as assessed by immunohistochemistry. Conclusion We have developed and validated a novel clinically applicable prognostic assay that at the time of first relapse identifies patients with unfavorable post-ASCT outcomes. Moving forward, it will be critical to evaluate the clinical use of RHL30 in the context of positron emission tomography–guided response assessment and the evolving cHL treatment landscape.
SP0097 Report of anatomy for the image report of the eular working group of anatomy for the image
Authors: I Möller
Journal: Annals of the Rheumatic Diseases (2017)

The EULAR Working Group for the Image became an official “working group” 2 years ago with the purpose of furthering anatomic study and education related to the human musculoskeletal system and relevant non-musculoskeletal structures important in the practice of rheumatology and, more specifically, rheumatologic imaging including but not limited the high-resolution musculoskeletal ultrasound and MRI. Studies performed: “Sonographic and anatomical description of the subtalar joint” – submitted for publication. “The anterior rotator cuff – a link between anatomy and ultrasound” – submitted for publication. “Learning model for successful ultrasound-guided synovial biopsy”: pending submission. New/Ongoing projects: Deep layer of the abdominal subcutaneous fat pad and cardiovascular risk: ultrasound measurement and relationship with visceral fat The mechanical function of the Hoffa fat pad as seen in a dynamic musculoskeletal ultrasound study. Ultrasound study of the neurovascular supply to the joints. The relevance of ligaments in inflammatory disorders of the articulations of the hand and wrist. The principles of anatomy as seen in musculoskeletal ultrasound. Activities promoted by the group: Barcelona Sonoanatomy IX and X under scientific endorsement of EULAR. Support: OMERACT: “Reliability exercise of synovitis at the subtalar joint”. In collaboration with the University of Barcelona: Certificate Course “Expert in Musculoskeletal Ultrasound”. <h3>Disclosure of Interest</h3> None declared
Relationship of PCSK9 and Urinary Thromboxane Excretion to Cardiovascular Events in Patients With Atrial Fibrillation
Authors: Daniele Pastori, Cristina Nocella, Alessio Farcomeni, Simona Bartimoccia, Maria Santulli, Fortunata Vasaturo, Roberto Carnevale, Danilo Menichelli, Francesco Violi, Pasquale Pignatelli, Mirella Saliola, Marco Antonio Casciaro, Domenico Ferro, Tommasa Vicario, Fabiana Albanese, Francesco Cribari, Alberto Paladino, Francesco Del Sole, Marta Novo, Vittoria Cammisotto, Paola Andreozzi, Tiziana Di Stefano, Patrizia Iannucci, Elio Sabbatini
Journal: Journal of the American College of Cardiology (2017)
The evolving role of the rheumatologist in the management of immune-related adverse events (irAEs) caused by cancer immunotherapy
Authors: Leonard Calabrese, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2017)

The rapid introduction of immunotherapies for cancer-targeting immunological checkpoints has led to a new class of toxicities that appear to be of autoimmune and or autoinflammatory origin. These disorders are now referred to as immune-related adverse events (irAEs) and pose considerable challenges to patient care in terms of how to optimally manage these formidable toxicities while allowing effective antitumoural therapy to continue. While rheumatologists will naturally be called on to manage those irAEs of rheumatic origin, we believe there is a need and an opportunity for rheumatologists to participate as central figures in this evolving field, in large part because of our familiarity with multiorgan autoimmune disease and our expertise in crafting and utilising both traditional and biological immune-based therapies. Rheumatologists urgently need education in this evolving field to be best positioned as contributors to care of such patients and investigators of the underlying mechanisms of these complications.
THU0496 Pulmonary symptoms as the first presentation of kawasaki disease in children
Authors: A Gupta, A Kumar, D Suri, S Singh
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Kawasaki disease (KD) is a medium vessel vasculitis which predominantly affects children less than 5 years of age. Though principal clinical features are mucocutaneous, KD in children may have multiple systemic manifestations, including pulmonary, which may create diagnostic difficulties for the treating physician. <h3>Objectives</h3> We describe our experience of managing children with uncommon pulmonary presentation of KD. <h3>Methods</h3> Five hundred and sixty five (565) children were diagnosed with KD during the period from January 1993 to December 2016 in Pediatric Rheumatology Clinic, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Nine children had pulmonary presentation of KD. A retrospective case review with respect to clinical presentation, radiological findings and treatment was done. <h3>Results</h3> Pulmonary presentation of KD was seen in 1.6% patients. Mean age at diagnosis of KD was 2.9years (range 9months – 4 years). 77.8% patients had no features suggestive of KD either on history or at presentation. First sign of KD was noted at a mean duration of 17.6 days (range 6–28 days) from the onset of symptoms. Periungual desquamation was the most common clinical sign seen in 66.6% patients followed by erythematous rash and perianal desquamation in 33.3% patients each. Persistent fever, thrombocytosis and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were seen in all patients. Microbiological investigations showed evidence of infection in only 2 patients – methicillin sensitive staphylococcus aureus in pus and positive mycoplasma agglutinin titre in one patient each. Parenchymal consolidation was the most common radiological finding (100%) followed by pleural effusion (55.5%), empyema (33.3%) and pneumothorax (11.1%). Coronary artery abnormalities were evident on echocardiography in 22.2% patients with dilatation of right coronary artery and left main coronary artery in 1 patient each. All patients received intravenous antimicrobials for pneumonia. Intravenous immunoglobulin (IVIG) at 2g/kg was given after a mean duration of 24 days of onset of fever. Fever, which was unresponsive to intravenous antimicrobials, responded to IVIG therapy in all except 2 patients which required a second dose of IVIG. 55.5% patients required intercostal drainage tube (ICDT) insertion, 2 patients required streptokinase and 1 patient each required video assisted thoracoscopic surgery (VATS) and decortication. Mean follow up period was 15.9 months (range 0–62 months). <h3>Conclusions</h3> Pulmonary involvement in patients with KD is uncommon and is less commonly recognized. Unresolving pneumonia in a child who continues to be febrile despite adequate antimicrobials with elevated inflammatory markers can be a clue towards the diagnosis of KD. Early recognition can prevent delays in diagnosis and shorten the hospital stay. <h3>Disclosure of Interest</h3> None declared
Clinical trials registered prospectively are less likely to veer from protocols, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Clinical trials that are registered prospectively on trial registries are more likely to be published without changes to the primary outcome or the study protocol than those not registered, a Finnish study has reported.1

“Journal editors, regulators, research ethics committees, funders, and sponsors should implement policies mandating prospective registration for all clinical trials,” said the study authors, led by An-Wen Chan, from the University of Toronto, Canada. …
THU0596 Rheumatology specialty training in european union countries
Authors: N Cikes, J Dudler, F Lioté, DE Bax, NDS Bax
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The Union of European Medical Specialists (UEMS) seeks through its speciality Sections and Boards (S&amp;B) to enhance the training of its doctors and to encourage and support the movement of doctors between countries. The Rheumatology S&amp;B has delegates from all EU countries and has developed a document (European Training Requirements (ETR) – at uemsrheumatology.eu) that provides guidance about the rheumatology curriculum. <h3>Objectives</h3> To determine: 1. The extent of use of the Rheumatology ETR by EU countries 2. The extent of use of logbooks in recording the progress of a trainee 3. If training centres are accredited 4. If national assessment programmes exist for trainees 5. If a country has quality assurance and enhancement processes in rheumatology training <h3>Methods</h3> A questionnaire was sent to all S&amp;B members asking questions in relation to all of the objectives with one follow-up questionnaire to non-responders. Verification of responses as well as obtaining responses from continuing non-responders occurred in December 2016. <h3>Results</h3> Nineteen countries responded. Most (18/19) have developed and implemented their own curriculum, often with the influence of the ETR, and also are using a logbook to record the progress of trainees. Training Centres are required to undergo accreditation in 15/19 countries. Another three countries are planning to introduce this. One country does not have an accreditation programme. After accreditation only 8 countries have quality assurance (QA) and enhancement (QE) programmes. In one of these countries the QA and QE processes are variable. Two other countries are either discussing or developing such processes. In 14 countries trainees are assessed to determine their suitability to become specialists. In one of these countries the approach is variable. Two other countries are planning to introduce assessments. Three countries do not assess their trainees. <h3>Conclusions</h3> Most EU countries have implemented their own, and varied, curricula for rheumatology training. All countries either use or are planning to use a portfolio, again variable in nature, to record trainees9 progress. Thus, it appears that at present any pan-European standardised curriculum or logbook will be of limited utility. Most countries require training centres to undergo accreditation. However, less than half of the countries have a continuation of quality assurance or quality enhancement processes after accreditation with some countries it seems having no plans to do so. At present, a specialist in one European country is required by European law to be recognised as such in another. This study did not determine the nature of the assessments undertaken in different countries but this is not of current relevance within Europe as regards the possible movement of a doctor from one country to another for professional reasons. <h3>Disclosure of Interest</h3> None declared
AB0631 The clinical consequences presence of ANTI-PM/SCL antibodies in systemic sclerosis
Authors: E Wielosz, M Dryglewska, M Majdan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Anti-PM/Scl (a-PM/Scl) antibodies are found in different systemic autoimmune disease such as polymyositis, dermatomyositis, systemic sclerosis (SSc), and overlap syndromes. According to literature they are detected in about 2% of patients with SSc, but their presence are more common in SSc with myositis overlap. Features positively associated with the presence of a-PM/Scl antibodies included younger age at disease onset, skeletal muscle involvement, calcinosis, inflammatory arthritis, and overlap disease. On the other hand interstitial lung disease and gastrointestinal symptoms were less frequent in SSc patients with a-PM/Scl. <h3>Objectives</h3> The aim of the study was to assess the clinical consequences presence of a-PM/Scl antibodies in patients with SSc. <h3>Methods</h3> The study was performed in 126 European Caucasian SSc patients (98-female and 28-male) hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases. Patients fulfilled the ACR classification criteria of SSc (59 have diffuse cutaneous SSc and 67 limited SSc). The study group were studied according to the presence of a-PM/Scl antibodies applying commercial test – EUROLINE Systemic Sclerosis Profile. Detection and interpretation of results was carried out electronically using the specific program Euroimmun– EUROLINEScan. The subtype of SSc, incidence of internal organ involvement and serological profile were determined in the whole group. Due to the presence of a-PM/Scl antibodies, patients were divided into two groups a-PM/Scl (+) SSc - 22 pts and a-PM/Scl (-) SSc- 104 pts. <h3>Results</h3> a-PM/Scl antibodies were detected in 22/126 patients with SSc (17,5.%) We showed a significant positive association with a-PM/Scl antibodies and myalgia or myosistis (p=0,0379), contractures (p=0,0002) and prevalence of overlap syndrome (p=0,0142). There were no relationship between the presence of a-PM/Scl antibodies and subtypes of SSc, other organ involvement, digital ulcers or calcinosis. <h3>Conclusions</h3> In SSc anti-PM/Scl antibodies are frequently associated with myalgia or myositis, contractures and overlap syndrome. <h3>Disclosure of Interest</h3> None declared
SP0029 Linking science to clinical practice: from the systematic literature review to the formulation of recommendations
Authors: R Landewe
Journal: Annals of the Rheumatic Diseases (2017)

Systematic literature review (SLR) is a scientific method to collect the available data in the literature regarding a specific research question, and to compare the quality of different studies, in order to arrive at the best possible answer. SLR is not the same as data-pooling. In contrast to what many clinicians think, SLR is clinical science and not "easy going", it takes a lot of time and effort, you can make mistakes, and you need to practice and obtain experience. A proper SLR is all but "low hanging fruit". Nevertheless, SLRs from the evidence base of guidelines, and as such are integral parts of them. This lecture will describe how SLRs should be translated into guidelines, and what pitfalls may prevent that the appropriate evidence will be enclosed in recommendations, or that too weak evidence gets a too prominent place. <h3>Disclosure of Interest</h3> None declared
AB0315 The potential association between rheumatoid arthritis and traditional cardiovascular risk factors: a meta-analysis of controlled studies
Authors: E Filhol, C Gaujoux-Viala, B Combe, J Morel, C Hua, A Nutz, C Lukas, F Flaisler
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic inflammation is the cornerstone of both rheumatoid arthritis (RA) and atherosclerosis. RA is currently considered as a cardiovascular risk factor. <h3>Objectives</h3> The aim of this systematic review was to assess the association between RA and the traditional cardiovascular risk factors (hypertension, dyslipidemia, diabete mellitus, and atherosclerosis) in RA patients in comparison to the general population. <h3>Methods</h3> We systematically searched literature (via Pubmed, Cochrane and abstracts from recent ACR and EULAR congresses) up to March 2016 for observational studies providing data concerning the presence of a traditional cardiovascular risk factor (among hypertension, dyslipidemia, diabetes mellitus, atherosclerosis) in patients with RA and in a control group. A meta-analysis of the relative risk (RR) concerning patients with RA in relation to the control group was performed for each cardiovascular risk factor. <h3>Results</h3> Out of 5714 screened references, 13 studies were included. Due to lack of data, atherosclerosis studies could not be included in this meta-analysis. For hypertension and diabetes, an increased risk was observed: RR =1.15 [95% CI 1.07–1.24], p=0.0003 and RR=1.11 [1.04–1.19], p=0.001, respectively. On the contrary, not any association was found with the dyslipidemia (RR=0.93 [0.77–1.12], p=0.43). <h3>Conclusions</h3> This meta-analysis highlights a moderate excess risk of hypertension and diabetes among patients with RA relative to the general population. A comprehensive identification of cardiovascular risk profile of RA is an opportunity to improve health management of these patients. Future research is crucial in order to establish to what extent the control of modifiable risk factors can improve cardiovascular outcome of these patients. <h3>Disclosure of Interest</h3> None declared
OP0235 A novel B cell specific IFN-I biomarker is associated with plasmablast numbers following B cell depletion therapy in SLE
Authors: YM El-Sherbiny, MY Md Yusof, E Hensor, A Rawstron, M Wittmann, P Emery, EM Vital
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> SLE is a Type I interferon (IFN-I) mediated disease with autoreactive B cells. Plasmablasts, the immediate progeny of B cells, are expanded in SLE and correlate with disease activity. We showed that their rate of regeneration after therapeutic B cell depletion with rituximab is variable and predicts relapse[1]. IFN-I has been shown <i>in vitro</i> to induce the differentiation of B cells into plasmablasts. We previously showed that therapeutic B cell depletion with anti-CD20 mAb leads to a transient reduction in CD20-negative plasmablasts, following which plasmablasts repopulate and their numbers predict clinical relapse. We developed tetherin as a flow cytometric, cell-specific marker for IFN-I response. <h3>Objectives</h3> To test the hypothesis that memory B cell tetherin determines the rate of plasmablast repopulation after rituximab. <h3>Methods</h3> 117 rituximab-treated SLE patients were studied prosectively using BILAG-2004 and flow cytometry. In 97 responders we tested plasmablasts at 6 months as a predictor of clinical relapse before 12 months to validate our previous finding. In 50 patients pre-rituximab and 28 patients post-rituximab we performed additional flow cytometry to measure tetherin on each cell subset. Expression of 18 ISGs was measured using Taqman on PBMCs and an ISG score calculated. <h3>Results</h3> We divided clinical responders to rituximab into earlier relapse (12 months) or later relapse (&gt;12 months). As in our published discovery cohort, plasmablasts were strongly predictive of clinical relapse. ROC analysis indicated that a plasmablast count of &gt;0.0008 x 10<sup>9</sup>/L at 6 months yielded 73% (95% CI 45–92%) sensitivity and 90% (95% CI 56–99%) specificity in predicting earlier relapse; area under the curve of 0.86. Plasmablast numbers after rituximab were associated with Memory B cell tetherin (R=0.38, p=0.047) but not ISG score (R=0.24, p=0.219) (Table 1). In Pre-rituximab there was no relationship between any IFN assay and plasmablast count. After rituximab treatment there was no correlation between plasmablast count and ISG expression, nor with monocyte or NK cell surface tetherin. However, memory B cell tetherin MFI was positively correlated with plasmablast count (Table 1). <h3>Conclusions</h3> Although interferon stimulated gene expression is commonly used to measure IFN-I activity, tetherin provides a cell-specific assay. We demonstrate that by measuring IFN-I response in B cells specifically, we could explain plasmablast differentiation, and thereby clinical outcome. Memory B cell tetherin is valuable to immunophetype SLE. <h3>References</h3> Vital et al. Arthritis Rheum. 2011 Oct;63(10):3038–47. <h3>Disclosure of Interest</h3> None declared
The epidermal growth factor network: role in oocyte growth, maturation and developmental competence
Authors: Dulama Richani, Robert B Gilchrist
Journal: Human Reproduction Update (2017)

WIDER IMPLICATIONS: An oocyte of high quality is imperative for fertility.Elucidating the fundamental molecular and cellular mechanims by which the EGF network regulates oocyte maturation and ovulation can be expected to open new opportunities in ART.This knowledge has already led to advances in oocyte IVM in animal models.Translation of such advances into a clinical setting should increase the efficacy of IVM, making it a viable treatment option for a wide range of patients, thereby simplifying fertility treatment and bringing substantial cost and health benefits.