tbuckley/cabot-search huggingface dataset:
AB0487 Neurologic manifestations and their impact on chronic damage in patients with antiphospholipid syndrome: result from a monocentric cohort
Authors: D Mazilu, D Potarniche, I Saulescu, A Borangiu, L Groseanu, C Constantinescu, V Vlad, F Berghea, V Bojinca, D Opris-Belinski, A Balanescu, D Predeteanu, R Ionescu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antiphospholipid syndrome (APS) is an autoimmune disease with wide clinical features and cumulative damage. The nervous system involvement is very broad and severe. <h3>Objectives</h3> The aim of this study is to analyze the impact of neurologic manifestations on Damage Index in Patients with APS (DIAPS). <h3>Methods</h3> All consecutive patients known with APS were included in our monocentric cohort. Data on medical history, clinical manifestations, aPL profile and medication were collected. DIAPS score was used to measure damage in each patient. <h3>Results</h3> Seventy six patients with APS were included: 11 patients with primary APS and 65 patients with secondary APS, with mean disease duration of 9.59±7.39years. Overall,35 patients (46.1%) had neurologic manifestations. Their mean disease duration was 9.2±5.76 years. Seven patients had primary APS and 28 patients had secondary APS. Six patients were on chronic oral anticoagulant therapy and low dose aspirin, 12 patients on oral anticoagulant alone and 15 patients on low dose aspirin. Transient ischemic attack was the first manifestation of APS in 4 patients (11.42%) at mean age of 29.5±10.96 years. Their mean DIAPS value was 7.75±4.19. Ischemic stroke was the first APS manifestation in 12 patients (34.28%) at mean age of 40.08±16.31years, with DIAPS mean value of 7.41±3.67. All of these patients have neurological sequelaes. The DIAPS value was higher in patients with neurologic manifestations (3±2.9 vs 5.71±3.62, p=0.001) and DIAPS value correlated significantly to neurologic manifestations (R=0.416, p&lt;0.000) reflecting it9s impact on cumulative damage in APS patients. <h3>Conclusions</h3> Neurologic manifestations in APS patients have a great impact on cumulative damage especially in patients presenting with ischemic stroke or transient ischemic attack as the first manifestation of APS. <h3>References</h3> M-C Amigo et al. Development and initial validation of a damage index (DIAPS) in patients with thrombotic antiphospholipid syndrome (APS). Lupus (2015) 24, 927–934. L.A. Martinez-Martinez et al. Damage Index in Patients with Thrombotic Antiphospholipid Syndrome: Retrospective Cohort Study. Ann Rheum Dis 2016;75:1065. <h3>Disclosure of Interest</h3> None declared
SP0043 Work retention rehabilitation in practice
Authors: Y Prior
Journal: Annals of the Rheumatic Diseases (2017)

This session aims to meet health professionals9 needs in recognising, examining, and identifying problems that patients with inflammatory arthritis (IA) face at work. We know that one in five people with inflammatory arthritis lose their job within five years of diagnosis and, once work disabled, they are unlikely to return to work. Therefore, preventive interventions targeted at work retention, which aim to help people to stay at work, are needed to avoid the transition from work instability to work disability. Rheumatology health professionals play an important role in identifying patients9 work problems at an earlier stage and helping them to stay at work. Currently, there are no set pathways to outline health professionals9 approach to identifying people with work problems and/or work rehabilitation interventions in the UK. Further, there is a need to train health professionals in the importance of the early recognition of these problems and evidence-based interventions to address work instability. This session will focus specifically on the rheumatology occupational therapy-led work rehabilitation taken place in a NHS setting in the UK. Using real life case studies, Dr Prior will discuss the standardised assessments used in identifying work problems, collaborative goal setting and work interventions to provide a snapshot of work rehabilitation in the context of clinical practice. <h3>Disclosure of Interest</h3> None declared
Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability
Authors: Esther Díaz-Rodríguez, Rosa M Agra, Ángel L Fernández, Belén Adrio, Tomás García-Caballero, José R González-Juanatey, Sonia Eiras
Journal: Cardiovascular Research (2017)

Abstract Aims In patients with cardiovascular disease, epicardial adipose tissue (EAT) is characterized by insulin resistance, high pro-inflammatory chemokines, and low differentiation ability. As dapagliflozin reduces body fat and cardiovascular events in diabetic patients, we would like to know its effect on EAT and subcutaneous adipose tissue (SAT). Methods and results Adipose samples were obtained from 52 patients undergoing heart surgery. Sodium-glucose cotransporter 2 (SGLT2) expression was determined by real-time polymerase chain reaction (n = 20), western blot, and immunohistochemistry. Fat explants (n = 21) were treated with dapagliflozin and/or insulin and glucose transporters expression measured. Glucose, free fatty acid, and adipokine levels (by array) were measured in the EAT secretomes, which were then tested on human coronary endothelial cells using wound healing assays. Glucose uptake was also measured using the fluorescent glucose analogue (6NBDG) in differentiated stromal vascular cells (SVCs) from the fat pads (n = 11). Finally, dapagliflozin-induced adipocyte differentiation was assessed from the levels of fat droplets (AdipoRed staining) and of perilipin. SGLT2 was expressed in EAT. Dapagliflozin increased glucose uptake (20.95 ± 4.4 mg/dL vs. 12.97 ± 4.1 mg/dL; P &lt; 0.001) and glucose transporter type 4 (2.09 ± 0.3 fold change; P &lt; 0.01) in EAT. Moreover, dapagliflozin reduced the secretion levels of chemokines and benefited wound healing in endothelial cells (0.21 ± 0.05 vs. 0.38 ± 0.08 open wound; P &lt; 0.05). Finally, chronic treatment with dapagliflozin improved the differentiation of SVC, confirmed by AdipoRed staining [539 ± 142 arbitrary units (a.u.) vs. 473 ± 136 a.u.; P &lt; 0.01] and perilipin expression levels (121 ± 10 vs. 84 ± 11 a.u.). Conclusions Dapagliflozin increased glucose uptake, reduced the secretion of pro-inflammatory chemokines (with a beneficial effect on the healing of human coronary artery endothelial cells), and improved the differentiation of EAT cells. These results suggest a new protective pathway for this drug on EAT from patients with cardiovascular disease.
The validation of the sit-to-stand test for COPD patients
Authors: Arnaud Chambellan, Simon Nusinovici, Trija Vaidya, Pierre-Antoine Gourraud, Claire de Bisschop
Journal: European Respiratory Journal (2017)

We read with interest the publication by Crook et al. [1] on the validation and responsive properties of the 1-min sit-to-stand (STS) test in patients with chronic obstructive pulmonary disease (COPD) undergoing pulmonary rehabilitation. The authors performed a comprehensive evaluation of the minimal clinical meaningful difference of the 1-min STS test. In our own dataset of patients from a multicentre study, this STS test exhibited similar level of reliability, intra-subject repeatability [2], and responsiveness to pulmonary rehabilitation with an estimated minimal important difference (MID) of three repetitions [3]. In their study, Crook et al. [1] emphasised the change in STS repetitions, which is better related to change in subjective outcomes (feeling thermometer notably), rather than with physical capacity outcomes such as the 6-min walk distance (6MWD). It is, after all, largely accepted that health-related quality of life (HRQoL) tools are the most sensitive in pulmonary rehabilitation, given the multimodal and patient-tailored interventions addressed in order to optimise benefits, not only focused on exercise training, but also on change in education and behaviour [4]. The change in the sit-to-stand test after a pulmonary rehabilitation is not influenced by the initial value <http://ow.ly/i2CI30eqprD>
FRI0057 Evaluation of the immunodominance of a histone h4 peptide in anti-ccp antibodies from rheumatoid arthritis patients
Authors: L Rodriguez-Martinez, C Regueiro, A Montes, E Perez-Pampin, A Mera-Varela, A Gonzalez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The anti-CCP assay identifies antibodies against endogenous citrullinated proteins that are not completely characterized. The histone H4 seems to be a prominent one according to a recent study (1), which found this protein specifically in the immune complexes from synovial fluid of anti-CCP positive RA patients. Only vimentin, among the previously proposed autoantigens, was present in those immune complexes, but its abundance was much lower than that of histone H4. In addition, a citrullinated H4-derived peptide, H4-c39/40, showed marked immunodominance since antibodies directed against this peptide were present in 100% of synovial fluid samples and in 92–94% of anti-CCP positive sera. These frequencies are much larger than the reported with other autoantigens. <h3>Objectives</h3> To confirm the immunodominance of the H4-c39/40 peptide in anti-CCP antibodies from RA patients by direct comparison with citrullinated peptides of two other potential autoantigens. <h3>Methods</h3> Five hundred and thirteen patients with established RA and 273 healthy controls were included. Antibodies against H4-c39/40, cFibB36–52 and cVim60–75 were evaluated using indirect ELISA. Concordance between positives and negatives was analyzed with the Goodman and Kruskal9s gamma coefficient (γ). In addition, Spearman9s rank correlation (r<sub>s</sub>) was used to analyze the correlation between levels of antibody titers. <h3>Results</h3> In contrast to the previous report (1), only 68.5% of the anti-CCP positive patients carried anti-H4-c39/40 antibodies. However, this frequency was higher than the observed with the other two peptides, 50.5% of anti-cFibB36–52 and 28.8% of anti-cVim60–75 positive patients. Consequently, a high concordance was found between anti-CCP and anti-H4-c39–40 antibodies (γ =0.95), which was moderately larger than that observed between anti-CCP and anti-cFibB36–52 antibodies (γ =0.86). In addition, anti-H4-c39/40 antibody titers were correlated with anti-CCP titers, but this correlation was similar to the observed between anti-cFibB36–52 and anti-CCP titers (r<sub>s</sub> =0.34 and 0.33, respectively). The anti-cVim60–75 antibodies, in turn, showed notably low concordance and low correlation with the anti-CCP antibodies. <h3>Conclusions</h3> Our results confirm that anti-H4-c39/40 antibodies are a significant component of the antibodies detected with the anti-CCP assay. However, immunodominance of this peptide was not as marked in our patients as the described in the original study. <h3>References</h3> Meng X, et al. PLoS One. 2016; 11(10):e0165501. <h3>Acknowledgements</h3> Funding was provided by grants of the Instituto de Salud Carlos III (Spain) PI14/01561 and RD12/009/008 with participation of FEDER. <h3>Disclosure of Interest</h3> None declared
Multimodality Radionuclide Imaging in a Patient With Hereditary Paraganglioma-Pheochromocytoma Syndrome
Authors: So Y. Yim, Valeria M. Moncayo, Francisco J. Pasquel, Raghuveer K. Halkar
Journal: Clinical Nuclear Medicine (2017)

Hereditary paraganglioma (PGL)-pheochromocytoma (PCC) syndrome is a genetic disorder caused by a mutation of the tumor suppressor gene SDHD that results in a predisposition for head and neck PGLs and PCCs. We present a case of a 33-year-old woman where F-FDG PET/CT showed areas of increased uptake in both the adrenal and cervical regions, consistent with PCCs and PGLs, respectively. Further imaging revealed that PCCs were I-MIBG avid, whereas the PGLs were In-octreotide avid. This demonstrates the varying sensitivities of different imaging modalities in regard to neuroendocrine tumors and the potential for treatment using multiple targeted therapies.
Audit of oxygen prescribing
Authors: A. Inglis
Journal: BMJ (2001)

# Treatment needs to be adjusted {#article-title-2}

EDITOR—The results of the audit of oxygen prescribing by Dodd et al raise numerous issues.1 The audit focused solely on the prescribed input rather than a measure of outcome. No reference was made to adjusting treatment with regard to the patient's oxygen saturation.2 Realistic goals for desired saturation would reduce the risks of either continued hypoxia or excessive treatment in severe chronic obstructive pulmonary disease.

The spectre of carbon dioxide narcosis was again raised. Intensivists repeatedly find that seriously hypoxic and exhausted patients have had their oxygen treatment reduced because of a raised arterial concentration of carbon dioxide. …
Scientific Challenges in the Risk Assessment of Food Contact Materials
Authors: Jane Muncke, Thomas Backhaus, Birgit Geueke, Maricel V. Maffini, Olwenn Viviane Martin, John Peterson Myers, Ana M. Soto, Leonardo Trasande, Xenia Trier, Martin Scheringer
Journal: Environmental Health Perspectives (2017)

Food contact articles (FCAs) are manufactured from food contact materials (FCMs) that include plastics, paper, metal, glass, and printing inks. Chemicals can migrate from FCAs into food during storage, processing, and transportation. Food contact materials' safety is evaluated using chemical risk assessment (RA). Several challenges to the RA of FCAs exist.We review regulatory requirements for RA of FCMs in the United States and Europe, identify gaps in RA, and highlight opportunities for improving the protection of public health. We intend to initiate a discussion in the wider scientific community to enhance the safety of food contact articles.Based on our evaluation of the evidence, we conclude that current regulations are insufficient for addressing chemical exposures from FCAs. RA currently focuses on monomers and additives used in the manufacture of products, but it does not cover all substances formed in the production processes. Several factors hamper effective RA for many FCMs, including a lack of information on chemical identity, inadequate assessment of hazardous properties, and missing exposure data. Companies make decisions about the safety of some food contact chemicals (FCCs) without review by public authorities. Some chemical migration limits cannot be enforced because analytical standards are unavailable.We think that exposures to hazardous substances migrating from FCAs require more attention. We recommend a) limiting the number and types of chemicals authorized for manufacture and b) developing novel approaches for assessing the safety of chemicals in FCAs, including unidentified chemicals that form during or after production. https://doi.org/10.1289/EHP644.
Additional value of quantitative expression of ZAP-70 and CD38 for prognostic factors in chronic lymphocytic leukemia.
Authors: Martin Klabusay, Viera Hrabcakova, Petr Coupek, Martin Trbusek, Michaela Pevna
Journal: Journal of Clinical Oncology (2017)

e19006 Background: Chronic lymphocytic leukemia (CLL) has heterogeneous clinical course. Identification of prognostic markers is important for proper management of disease. Cytogenetics, IgVH mutation status, TP53 functional status, CD38, ZAP-70 and CD49d expression are accepted prognostic factors in CLL. ζ-chain-associated protein kinase 70 (ZAP-70) is associated with disease progression. However, measurement of ZAP-70 and CD38 expression relies on qualitative flow cytometry. Authors tested hypothesis whether quantitative analysis of markers can improve information about prognosis of CLL. Methods: 217 CLL patients were included; diagnosis was made from peripheral blood by morphology and immunophenotyping by flow cytometry with common antibodies. Expressions of intracellular ZAP-70 and surface CD38 were measured using quantitative fluorescence cytometry. Standardized fluorescent microparticles were used to quantify molecules of equivalent soluble fluorochrome (MESF units). Analysis of rearrangement of the IgVH gene was performed according to the European recommendation. Deletions at 11q22-q23 ( ATM), 17p13 ( TP53), 13q34 ( RB1) loci and trisomy of chromosome 12 were detected by I-FISH. Results: Patients’ ages ranged from 33 to 86 years and included all Rai stages. Expression of ZAP-70 ranged from 546 to 5,955 MESF, CD38 from 1,886 to 31,619 MESF. 48% patients embodied mutated and 52% unmutated IgVH status. In cytogenetics, del(13q) was detected in 59%, trisomy 12 in 13%, del(11q) in 21%, and del(p53) in 8% of patients. IgVH (in %) was plotted against ZAP-70 (in MESF) and patients were divided into high (HR) and low risk (LR) groups by cluster analysis based on Kaplan-Meier overall survival curves. Patients in HR group had significantly poorer prognoses (p = 0.0001) than those in LR group. When patients from HR group were clustered according to CD38 expression, very high risk (VHR) group with high CD38 and significantly worse prognosis (p = 0.035) was identified. Conclusions: We have demonstrated that quantitative ZAP-70 and CD38 expressions cannot replace IgVH analysis, but, contrary to that, addition of quantitative data can further specify prognoses of patients with CLL.
SP0193 Principles of non-pharmacological management of fibromyalgia
Authors: JE Vriezekolk
Journal: Annals of the Rheumatic Diseases (2017)

Having fibromyalgia greatly impacts person9s mental and physical wellbeing, his activities of daily living, and the society at large. Despite scientific progress to unravel the aetiology of fibromyalgia syndrome, no cure is yet available. The management of fibromyalgia comprises both pharmacological and non-pharmacological treatment option to alleviate the symptom burden of the disease. The recently published EULAR revised recommendations for the management of fibromyalgia<sup>1</sup>, proposes that the management of fibromyalgia should take the form of a graduated approach with the aim of improving health-related quality of life. It should focus first on non-pharmacological treatment, including education, self-management and physical therapy with graded physical exercises. In this talk a brief overview of the current evidence regarding non-pharmacological care in fibromyalgia will be given. The importance of patients9 self-management, (tailored) interventions to support self-management, and its dissemination and implementation in clinical practice will be highlighted. <h3>References</h3> Macfarlane GJ, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis 2017;76:318–328. <h3>Disclosure of Interest</h3> None declared
A novel role for ciliary function in atopy: ADGRV1 and DNAH5 interactions
Authors: Pierre-Emmanuel Sugier, Myriam Brossard, Chloé Sarnowski, Amaury Vaysse, Andréanne Morin, Lucile Pain, Patricia Margaritte-Jeannin, Marie-Hélène Dizier, William O.C.M. Cookson, Mark Lathrop, Miriam F. Moffatt, Catherine Laprise, Florence Demenais, Emmanuelle Bouzigon
Journal: Journal of Allergy and Clinical Immunology (2017)
Reduced Structural Connectivity in Frontostriatal White Matter Tracts in the Associative Loop in Schizophrenia
Authors: James J. Levitt, Paul G. Nestor, Laura Levin, Paula Pelavin, Pan Lin, Marek Kubicki, Robert W. McCarley, Martha E. Shenton, Yogesh Rathi
Journal: American Journal of Psychiatry (2017)

Objective: The striatum receives segregated and integrative white matter tracts from the cortex facilitating information processing in the cortico-basal ganglia network. The authors examined both types of input tracts in the striatal associative loop in chronic schizophrenia patients and healthy control subjects. Method: Structural and diffusion MRI scans were acquired on a 3-T system from 26 chronic schizophrenia patients and 26 matched healthy control subjects. Using FreeSurfer, the associative cortex was parcellated into ventrolateral prefrontal cortex and dorsolateral prefrontal cortex subregions. The striatum was manually parcellated into its associative and sensorimotor functional subregions. Fractional anisotropy and normalized streamlines, an estimate of fiber counts, were assessed in four frontostriatal tracts (dorsolateral prefrontal cortex-associative striatum, dorsolateral prefrontal cortex-sensorimotor striatum, ventrolateral prefrontal cortex-associative striatum, and ventrolateral prefrontal cortex-sensorimotor striatum). Furthermore, these measures were correlated with a measure of cognitive control, the Trail-Making Test, Part B. Results: Results showed reduced fractional anisotropy and fewer streamlines in chronic schizophrenia patients for all four tracts, both segregated and integrative. Post hoc t tests showed reduced fractional anisotropy in the left ventrolateral prefrontal cortex-associative striatum and left ventrolateral prefrontal cortex-sensorimotor striatum and fewer normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum and in the left and right ventrolateral prefrontal cortex-sensorimotor striatum in chronic schizophrenia patients. Furthermore, normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum negatively correlated with Trail-Making Test, Part B, time spent in healthy control subjects but not in chronic schizophrenia patients. Conclusions: These findings demonstrated that structural connectivity is reduced in both segregated and integrative tracts in the striatal associative loop in chronic schizophrenia and that reduced normalized streamlines in the right-hemisphere dorsolateral prefrontal cortex-sensorimotor striatum predicted worse cognitive control in healthy control subjects but not in chronic schizophrenia patients, suggesting a loss of a "normal" brain-behavior correlation in chronic schizophrenia.
New Advances and Challenges of Targeting Cancer Stem Cells
Authors: Nurmaa K. Dashzeveg, Rokana Taftaf, Erika K. Ramos, Luke Torre-Healy, Anastasia Chumakova, Daniel J. Silver, Tyler J. Alban, Maksim Sinyuk, Praveena S. Thiagarajan, Awad M. Jarrar, Soumya M. Turaga, Caner Saygin, Erin Mulkearns-Hubert, Masahiro Hitomi, Jeremy N. Rich, Stanton L. Gerson, Justin D. Lathia, Huiping Liu
Journal: Cancer Research (2017)

Abstract The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20–23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop. The reported advances of CSC research and therapies fostered new collaborations across national and international borders, and inspired the next generation's young scientists. Cancer Res; 77(19); 5222–7. ©2017 AACR.