tbuckley/cabot-search huggingface dataset:
SAT0397 Safety and immunogenicity of 23-valent pneumococcal vaccine in sle patients
Authors: G. Tarasova, B. Belov, D. Bukhanova, S. Soloviev, E. Aseeva, T. Popkova, M. Cherkasova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immunisation with pneumococcal vaccine is the key prophylactic measure to protect patients with systemic lupus erythematosus (SLE) against severe respiratory infections. <h3>Objectives</h3> To study the efficacy and immunogenicity of 23-valent polysaccharide pneumococcal vaccine in SLE pts. <h3>Methods</h3> The study included 30 SLE pts, 27 females, 3 males, aged 19–62 y, the follow up (FUP) was 12 mo. Disease activity at vaccination was high – in 1 patient, moderate – in 4 pts, and low – in 20 pts; drug-induced remission – in 5. Therapy: 29 pts were on glucocorticoids (GCs), 23 – on hydroxychloroquine, 14 – on cytostatic (CS) drugs, 9 – on biologic diseases modifying anti rheumatic drugs (bDMARDs): 4 – on rituximab, and 5 – on belimumab. One dose (0,5 mL) of 23-valent polysaccharide pneumococcal vaccine was administered subcutaneously. Standard clinical examination and lab tests were performed, and vaccine immunogenicity was determined by measuring antibody (AB) levels against <i>Streptococcus pneumoniae</i> (VaccZymeTM PCP IG 2 panels (The Binding Site Ltd, Birmingham, UK)) at control visits. <h3>Results</h3> Local injection site reactions of varying intensity were registered in 19 (63,3%) pts, lasting from 2 to 7 days. One patient developed an immediate hypersensitivity reaction – the Arthus phenomenon-type. All accompanying symptoms completely resolved within 7 days with the intake of antihistaminic drug and local use of GCs. Mean (Me (25,75 percentiles)) SLEDAI scores for SLE activity prior to and 1 year after vaccination did not differ significantly: 2 (2;4) and 2 (0;4), respectively. Mean values of SLE immunological activity parameters (a-dsDNA, C3 and C4 components of the complement) also did not differ significantly, with a visible trend for a-dsDNA reduction and complement components increase: C3 (0,86 (0,81;1.07) and 0,93 (0,86;1,05)); C4 (0,16 (0,13;0,19) and 0,18 (0,13;0,19), respectively. (table 1) <h3>Conclusions</h3> Obtained results demonstrate the safety and immunogenicity of 23-valent pneumococcal vaccine in SLE patients during one year FUP. The negative effect of bDMARDs on post-vaccination response was noticed. Future studies of vaccine efficacy and safety are needed in larger SLE populations. <h3>Disclosure of Interest</h3> None declared
Fibroblast growth factor 9 (FGF9) stimulates migration of endothelial and ovarian cancer cells
Authors: Neali D. Hendrix, Kathleen R. Cho
Journal: Cancer Research (2005)

5658  Tumors must induce growth of new blood vessels (neoangiogenesis) in order to grow and metastasize. Angiogenesis requires several cellular processes including endothelial cell proliferation, migration, and extracellular matrix degradation. Selected members of the fibroblast growth factor (FGF) family have been reported as strong angiogenic agents. We recently identified FGF9 as a downstream target of the canonical Wnt signaling pathway and FGF9 is significantly upregulated in ovarian endometrioid adenocarcinomas with deregulated Wnt signaling. However, the functional consequences of increased FGF9 expression in ovarian cancer cells are largely unknown. Others have previously shown, and we confirmed, that FGF9 does not effectively stimulate proliferation of endothelial cells. However, we found that recombinant human FGF9 strongly stimulates proliferation of SV40T-Ag life-extended human ovarian surface epithelial cells (IOSE-80). Moreover, FGF9 enhanced migration of primary human umbilical vein endothelial cells (HUVECs) as well as ovarian carcinoma cells (OVCA420) using wound scratch assays. Additional studies of FGF9’s effects on ovarian cancer cell migration and invasion are in progress. The effects of FGF9 on endothelial and tumor cell migration and epithelial proliferation provide insight into the mechanisms by which increased FGF9 expression likely contributes to ovarian cancer progression.
Tracking T Cell Activation By OX40 Immuno-PET: A Novel Strategy for Imaging of Graft Versus Host Disease
Authors: Federico Simonetta, Israt S. Alam, Aaron T. Mayer, Surya Murty, Ophir Vermesh, Toshihito Hirai, Tomomi Nobashi, Kenneth Lau, Sanjiv S. Gambhir, Robert S. Negrin
Journal: Blood (2018)
FRI0590 Ultrasound examinatoin of the wrist joints: frequency of cristal deposits (CHONDROCALCINOSIS) in patients with different arthropathies
Authors: R. Osipyants, M. Eliseev, S. Vladimirov, K. Ilinykh
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hand involvement in the rheumatic diseases is often precocious and predominant as compared to other skeletomuscular regions. The Ultrasound (US) has an important role in early calcium pyrophosphate deposition disease (CPPD) diagnosis. Recent studies suggest a positive associated of CPPD and other rheumatic disease.<sup>1,2</sup> <h3>Objectives</h3> To investigate the frequency of the US features of chondrocalcinosis (CC) at the triangular fibrocartilage complex (TFC) of the wrist in patients (pts) with different arthropathies. <h3>Methods</h3> A total of forty persons were included in the study and were divided into 4 groups (on ten in each group): basic group – CPPD pts (crystal-proven at synovial fluid analysis; median age 58.5 (range 45–63) years; 6M/4F) and the control groups – rheumatoid arthritis pts (RA, ACR/EULAR 2010 age 50.5 (44–56) years; 3M/7F), psoriatic arthritis pts (PsA, CASPAR criteria; age 50(37-59) years; 3M/7F), healthy volunteers (age 37.5 (33–55) years; 3M/7F). All subjects were carefully age and gender matched with the CPPD pts. US examinations ("Voluson-i" (GE, USA), 4–13 MHz probe) were performed by one examiner. TFC of the wrist was assessed to detect US findings of crystal deposits.<sup>3</sup> The Mann-Whitney U-test was applied for intergroup comparison. <h3>Results</h3> In all CPPD pts (100%) CC of TFC was detected in at least one joint. In the control groups intra-cartilaginous hyperechoic spots were found in 6 of 10 cases with RA (60% vs. 100%, p=0.029), in 2 with PsA (20% vs. 100%, p&lt;0.01), 3 cases in healthy volunteers (30% vs. 100%, p&lt;0.01). <h3>Conclusions</h3> The results of the present study indicate that US is a very sensitive and specific technique for detecting calcifications in patients with crystal-related arthropathy. The US findings were detected a trend of association between CC and RA. However, more studies, involving a larger number of pts, are required. <h3>References</h3> [1] Sabchyshyn V, et al. Concurrence of the rheumatoid arthritis and calcium pyrophosphate deposition disease: a case collection and review of the literature. Sem Arthr Rheum2017Nov. http://dx.doi.org/10.2016/j.semarthrit.2017.11.009 [2] Gersing A, et al. Evaluation of chondrocalcinosis and associated knee joint degeneration using MRI imaging: data from osteoarthritis initiative.Eur Radiol2017Jun;27(6):2497–2506. doi:10.1007/s00330-016-4608-8 [3] Filippou G, et al. Extend and distribution of CPP deposition in patients affected by calcium pyrophosphate dihydrate deposition disease: an ultrasonographic study. Ann Rheum Dis2013;72(11):1836–9. http://dx.doi.org/10.1136/annrheumdis-2012-202748 <h3>Disclosure of Interest</h3> None declared
FRI0337 Factors associated with poor therapeutic adherence to hydroxychloroquine during systemic lupus
Authors: Y. Rozban, H. Devilliers, M. Hié, M. Pha, A. Mathian, F. Cohen-Aubart, J. Haroche, J.-S. Hulot, N. Zahr, Z. Amoura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Poor adherence to medication regimens is a major cause of relapse during systemic lupus erythematosus (SLE). Hydroxychloroquine (HCQ), the main therapy of SLE, has a long half-life. Thus, undetectable blood HCQ concentrations can be used to identify patients who do not take their treatment <h3>Objectives</h3> To identify the determinants of poor therapeutic adhesion in patients with SLE. <h3>Methods</h3> Case-control, retrospective, monocentric study. The cases were enrolled in our centre from 02/11/2011 to 13/01/2015 according to the following criteria: SLE defined according to ACR classification criteria and blood concentration of HCQ &lt;100 ng/ml after a minimum of 2 months on therapy. For each case, the matched control was a lupus patient, enlisted from our centre the same week, with an HCQ dose greater than or equal to 800 ng/ml. Case and control characteristics were compared using standard tests and a uni-multivariate logistic regression. <h3>Results</h3> One hundred and fifty patients were included, 75 cases (68 women) and 75 controls (72 women), with an average age of 35.7 years (±11.3 years) vs 35.6 years (±10.6 years). Most patients had inactive lupus (3 patients had SLEDAI ≥4), 27% of them had benefited from therapeutic education sessions. The average dosage of HCQ was 1110 ng/ml within the control group. In our univariate analysis, nonadherent patients lived significantly further away from the centre than adherent patients (median distance [interquartile range]: 22<sup>11–52</sup> vs 14 km [5.9–35], respectively, p=0.03) and were more likely to be unemployed, (23 vs 8%, respectively, p=0.006). Nonadherent patients had less often benefited from the patient's therapeutic education program (18 vs 35%, respectively, p=0.018), were taking less treatment (3 vs 4, respectively, p=0.008), had a significantly lower level of education (61% compared to 89% of patients with at least a bachelor's degree, p&lt;0.001). In our multivariate analysis, a level of education below the A levels was the strongest factor explaining poor therapeutic adherence, OR (IC 95): 4.09 (1.5–10.8). <h3>Conclusions</h3> The main drivers of therapeutic adherence during SLE are socio-economic factors. The least educated and most disadvantaged patients are most likely to display poor therapeutic adherence. Targeted preventive actions and enhanced therapeutic education should be provided to them. <h3>Disclosure of Interest</h3> None declared
AB0474 The clinical effectiveness and cost savings of tapering biologic dmards in patients with inflammatory arthritis at a uk district general hospital
Authors: W.P. Lee, R. Manhas, V. Sebbage, S. Kyle
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Biologic DMARDs (bDMARDs) have led to substantial improvement in clinical outcomes for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial/peripheral spondyarthropathy(SpA), making remission a realistic target. Current guidelines suggest clinicians should consider tapering after achieving remission in RA.<sup>1</sup> Nevertheless, the optimal approach for tapering bDMARDs remains unknown and un-standardised across conditions.<sup>2</sup> <h3>Objectives</h3> To evaluate the tapering strategies on 3 major rheumatological disease entities (RA, PsA, SpA), the number of patients successfully tapered and the total cost saving from successful tapering. <h3>Methods</h3> The study was conducted at North Devon District Hospital in Barnstaple, UK and includes all bDMARDs users up until 31st December 2017. The tapering strategy was identified from hospital notes. Patients who are deceased, lost to follow-up or discontinued bDAMRDs due to contraindication or adverse effects were excluded. Successful tapering is defined as patient on tapered dose or had their biologics withdrawn and remains at target treatment level (RA: DAS-28 &lt;2.6; PsA:&lt;3 tender joints and &lt;3 swollen joints; SpA: BASDAI &lt;4). <h3>Results</h3> There are a total of 298 patients: 174 RA; 59 PsA; 57 SpA; 8 other diagnoses. 94 patients (31.5%) had attempted tapering: 52 RA, 18 PsA, 22 SpA. 60 (20.1%) successfully tapered their bDMARDs: 34 RA (56.7%); 13 PsA (21.7%); 13 SpA (21.7%). Out of 34 RA, 30 seropositive; 4 seronegative; 24 co-prescribed with synthetic DMARDs, 10 on monotherapy. Out of 13 PsA, 8 co-prescribed with synthetic DMARDs; 5 on monotherapy. 59 tapered by increasing interval of subcutaneous treatment. Only 1 RA patient tapered its IV dose of tocilizumab. This patient is excluded from the final analysis. Tapering of subcut bDAMRDs therapy by disease and price (table 1). Number rounded to 2 decimal points. <h3>References</h3> [1] Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis2014;73:492–509. [2] Lenert A, Lenert P. Tapering biologics in rheumatoid arthritis: a pragmatic approach for clinical practice. Clin Rheum2017;36:1–8. <h3>Disclosure of Interest</h3> None declared ADA – adalimumab; TOC – tocilizumab; ETN – etanercept; GOL – golimumab; CZP – certolizumab pegol <h3>Conclusions</h3> In our study, 20% of bDAMRDs users successfully tapered their dose. The total cost saving is significant at £359,912.98 over the tapered period, of which £249,321.19 (69%) in RA; £39,171.01 (11%) in PsA; £71,420.78 (20%) in SpA.
Abstract 220: Magnetic Resonance Imaging in Children with Cardiac Complications of Kawasaki Disease: a Comparison with Echocardiography and Conventional Coronary Angiography
Authors: Michael Khoury, Cedric Manlhiot, Lars Grosse-Wortmann, Shi-Joon Yoo, Michael Seed, Andrew N Redington, Brian W McCrindle
Journal: Circulation (2015)

Background: MRI is a potentially sensitive, specific, and non-invasive imaging modality that may be used in the detection and monitoring of KD cardiac complications. Its utility relative to the more commonly used imaging modalities of echocardiography and conventional coronary angiography has not been optimally established. Methods: We compared concomitant clinical data, echocardiography, MRI, and angiography findings for children with coronary artery aneurysms. Results: MRI and angiograms were performed within 1 month of each other for 15 patients (mean age 7 years, 80% male) at a mean of 4.2 years after diagnosis. Coronary artery bypass grafting (CABG) had been performed in 8 patients (53%). For 7 patients (47%), aneurysms were seen on MRI that were not seen on echocardiography. Wall motion abnormalities were reported in 7 subjects (47%). These were characterized on both echocardiography and MRI for all. MRI identified perfusion defects in 6 patients (40%) and evidence of myocardial scar in 9 patients (60%). Extra-cardiac aneurysms were identified in 5 patients (33%) on MRI. MRI showed strong correlation with angiograms regarding aneurysm location. MRI was limited in the assessment of bypass grafts in 4 of the 8 (50%) patients who had undergone CABG. Three patients (20%) had stenosis or thrombosis identified on angiography that were not appreciated on MRI. Angiograms provided added information regarding flow, stenoses, vascular morphology and/or calcification in 8 patients (53%). Collateral artery anatomy that was not appreciated on echo and MRI were reported on angiograms in 3 patients (20%). Conclusions: MRI provides a valuable and comprehensive assessment of the cardiac sequelae of KD, though is limited in its assessment of CABG, stenoses, and thrombosis. MRI may be an important component of non-invasive imaging surveillance of children with important coronary artery involvement.
Dose-adjusted EPOCH plus rituximab improves the clinical outcome of young patients affected by double expressor diffuse large B-cell lymphoma
Authors: A. Dodero, A. Guidetti, A. Tucci, F. Barretta, M. Novo, L. Devizzi, A. Re, A. Passi, A. Pellegrinelli, G. Pruneri, R. Miceli, A. Testi, M. Pennisi, M. C. Di Chio, P. Matteucci, C. Carniti, F. Facchetti, G. Rossi, P. Corradini
Journal: Leukemia (2019)
A&amp;E registrar is struck off for repeated sexual harassment of staff nurse
Authors: Clare Dyer
Journal: BMJ (2019)

A locum registrar in an emergency department who repeatedly sexually harassed a staff nurse over two years has been struck off after a medical practitioners’ tribunal refused to believe his claim that she had pursued him.

Udodiri Okpara, 48, frequently stated his admiration for the young nurse’s bottom and brushed against it repeatedly, the tribunal heard, at one point standing with his groin against it while the nurse took blood from a patient.

His behaviour escalated, the tribunal found, culminating in an incident where he followed her into the sluice room, held her from behind and put his hand down her trousers. When she asked him to stop, he said “please, just …
THU0397 The prognostic value of autoantibodies in systemic sclerosis and a two-year follow-up of forced vital capacity
Authors: A.A.A. Mohamed, M. Hassanien
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is a connective tissue disease involving the skin and internal organs of the body. Affection of the lungs and the vascular system significantly increases the morbidity and mortality. Controlling disease progression represents a challenge in clinical practice. <h3>Objectives</h3> We aimed to address prognostic factors of disease activity and study the progress of interstitial lung disease (ILD) under conventional disease modifying anti-rheumatic drugs (DMARDs) therapy. <h3>Methods</h3> Data of SSc patients (limited or diffuse) followed up in the Rheumatology Department Clinics throughout the past 2 years were collected for a retrospective study. The positivity of Antinuclear (ANA), Anti-centromere (ACA) and Anti-Scl70 antibodies was gathered from patients' data. Disease activity was assessed by the European Scleroderma Study Group (EScSG) activity index. Forced vital capacity (FVC) was used to mark the progress of ILD. Friedman and Wilcoxon signed rank tests were used for comparison of paired data as appropriated. Mann-Whitney U test, Kruskal-Wallis test and Chi-Square test were used to compare between two or more groups. <h3>Results</h3> The data of 42 SSc patients (59.5% limited SSc and 40.5% diffuse SSc) with a mean age 40±12 years were enrolled. 83.3% of the patients showed ANA positivity. ACA was positive in 28.6% of the patients and Anti-Scl70 in 23.8% while 47.6% of the patients were negative for both. DMARDs were indicated according to organ involvement, and changes were made according to breakthrough events. Low scores of EScSG were noticed in the ACA +ve group compared to intermediate scores in the Scl70 +ve group and high scores in the negative group at baseline (p=0.082) and 24 month follow-up (p=0.045). The frequency of pitting digital ulcers at baseline was lowest in the ACA +ve group compared to the highest frequency in the negative group (p=0.026), however, there was no difference between the groups at the 24 month follow-up. ANA did not affect the activity throughout the studied period. Follow up of FVC in the two years with different DMARDs is illustrated in figure 1. Patients followed on methotrexate (MTX) after cyclophosphamide (CYC) or mycofenolate (MMF) had raised FVC (p=0.033 and p=0.054 respectively) comparable to azathioprine (AZA) after CYC or MMF (p=0.031 and p=0.27 respectively). <h3>Conclusions</h3> ACA is proposed to be a marker of low disease activity and good response to therapy. Despite the risk of inducing ILD, MTX maintained a favourable effect on FVC throughout a follow-up period. <h3>Disclosure of Interest</h3> None declared
Abstract 21344: Mutations in <i>CACNA1C</i> and <i>KCNE2</i> Genes are Associated With Brugada Syndrome and Epilepsy
Authors: Dan Hu, Yuesheng Wu, Ryan Pfeiffer, Tabhita Carrier, Sami Viskin, Hector Barajas Martinez
Journal: Circulation (2017)

Introduction: Cardiac arrhythmias are generally associated with abnormal mutations in ion channel genes. Epilepsy is a disorder of neuronal function, which also involves abnormal channel function. Our Hypothesis: now increasing by demonstration that the etiologies of Brugada syndrome (BrS) and epilepsy may partly overlap. However, only a few genetic studies have addressed a possible link between cardiac and neural channelopathies. Methods: The suspected case and family were underwent thorough medical examination. Fifteen candidate genes were screened for ion channels by direct sequencing. Ion channel variants were cloned by site-directed mutagenesis and studied using patch clamp and confocal microscopy techniques in TSA201 cells. Results: A 36 y/o male with epilepsy showing typical type 1 Brugada pattern ECG during flecainide challenge test and under antiepileptic medication (valproic acid). Cardiac evaluation included a normal echocardiogram and exercise stress test. We identified two mutations (D2130N and A1717G) in CACNA1C and one in KCNE2 (T10M). All mutations are highly conserved. The variants in CACNA1C were located in C terminal and the one in KCNE2 was in N terminal. Functional studies in CACNA1C mutants were co-expressed with CACNB2b and CACNA2D1 . At 0 mV, peak ICa densities were reduced by 85% and 70% in D2130N and A1717G vs. WT respectively. Significant kinetic alterations included a negative shift in V1/2 of inactivation, and positive shift in V1/2 of activation, for D2130N and A1717G, respectively. Confocal study showed D2130N and A1717G conjugated to YFP trafficked normally to the cell membrane. We found a gain-of-function in Ito current when T10M- KCNE2 was co-expressed with KCND3 channels by 55% relative to WT. Conclusion: Our results suggest for the first time that several mutations in CACNA1C leads to a loss of function in ICa and thus can contribute to the development of BrS phenotype. T10M- KCNE2 produces a gain of function in Ito, which further aggravates BrS. Meanwhile, as previously reported, T10M- KCNE2 also produces a loss-of-function of IKr, so it is reasonable to deduce that the mutation is probably responsible for the epilepsy. It once again provides the evidence that anti-epilepsy drug could unmask potential Brugada ECG.
Emergence of enterovirus D68 clade D1, France, August to November 2018
Authors: Antonin Bal, Marina Sabatier, Thierry Wirth, Marianne Coste-Burel, Mouna Lazrek, Karl Stefic, Karen Brengel-Pesce, Florence Morfin, Bruno Lina, Isabelle Schuffenecker, Laurence Josset
Journal: Eurosurveillance (2019)

We report a seasonal increase of enterovirus D68 (EV-D68) cases in France, with 54 cases detected between 19 August and 14 November 2018. Molecular typing revealed that 20 of 32 of the isolates belonged to clade D1, only sporadically detected before in France. Median age of D1-cases was 42 years, 10 developed severe respiratory signs and one had neurological complications. The 2018-D1 viruses showed a genetic divergence of 3.34 % with D1 viruses identified previously.