tbuckley/cabot-search huggingface dataset:
Copeptin in the Diagnosis of Diabetes Insipidus
Authors: Wiebke Fenske, Julie Refardt, Mirjam Christ-Crain
Journal: New England Journal of Medicine (2018)

Copeptin in the Diagnosis of Diabetes InsipidusTo the Editor: In their study of the value of copeptin for diagnosing diabetes insipidus, Fenske et al. (Aug. 2 issue) 1 overlook two possible methodologic flaws.First, some of their patients appear to have had an element of a solute diuresis.For example, among patients with primary polydipsia, the product of the baseline median urine osmolality (408 mOsm per kilogram) and a urine volume of 4 liters per day or more indicates that in some patients the daily urine solute load was more than 1600 mOsm, which greatly exceeds the normal value (approximately 10 mOsm per kilogram per day). 2,3Second, the water-deprivation test was incomplete.The goal is to raise the serum sodium and endogenous vasopressin levels sufficiently to induce maximal urine concentration, as shown by stability of the urine osmolality. 4,5This critical step was omitted.Therefore, we cannot know whether the stimulus was adequate and whether restricting water longer would have changed the results.That the serum sodium levels were notably higher after the administration of hypertonic saline than after water deprivation suggests that it might have.Thus, the authors' conclusion that measurement of hypertonic saline-stimulated copeptin is superior to water-deprivation testing seems premature.
SP0002 Psa beyond the typical poly-articular phenotype: how to deal with this in clinical practice?
Authors: E. Nikiphorou
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> This lecture will focus on the case of a psoriatic arthritis (PsA) patient presenting primarily with entheseal disease rather than the usual poly-articular phenotype. The case discusses issues around misinterpretation of signs and symptoms leading to inappropriate diagnoses and failure to early disease recognition and therefore treatment. Consequences of delayed treatment and less typical presentations of PsA will be discussed in greater detail during the session, highlighting important diagnostic and management aspects of disease, relevant to routine clinical practice. <h3>Disclosure of Interest</h3> None declared
OP0008 Modelling an autoinflammatory immunoproteasome disease nakajo-nishimura syndrome with human pluripotent stem cell-derived myeloid cell lines
Authors: M. Saito
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Nakajo-Nishimura syndrome (NNS) is an immunoproteasome-associated autoinflammatory disorder caused by a mutation of PSMB8 gene.<sup>1</sup> Although dysfunction of immunoproteasome causes various cellular stresses attributed to the overproduction of inflammatory cytokines and chemokine in NNS, precise underlying mechanisms of autoinflammation are still largely unknown. <h3>Objectives</h3> We aim to investigate and understand the detailed mechanisms and signal pathways in NNS and to seek potential therapeutic candidates. <h3>Methods</h3> We established a panel of isogenic pluripotent stem cell (PSC) lines with the homozygous G201V mutation in PSMB8 gene using CRISPR/Cas9- mediated genome editing system. Myeloid cell lines (MLs) were established from each clone and used for functional analysis.<sup>2 3</sup> <h3>Results</h3> Immunoproteasome activity of PSMB8-mutant PSC-derived MLs (MTMLs) reduced even without stimulation, compared to that of the isogenic wild-type counterparts. When stimulated, MT-MLs showed overproduction of inflammatory cytokines and chemokines, with elevated reactive oxygen species (ROS). The levels of phosphorylated p38 MAPK and STAT1 also increased. Treatment with a p38 MAPK inhibitor, a JAK inhibitor and anti-oxidants dose-dependently decreased the abnormal production of cytokines and chemokines in MT-MLs. Both unstimulated and stimulated MT-MLs showed distinct transcriptional profiles, indicating the ML-MLs were already in a 'primed' state before stimulation. <h3>Conclusions</h3> The current PSC models revealed a specific ROS-mediated inflammatory pathway and provide a platform for studying the pathophysiology of NNS and searching for the alternative therapeutic options for NNS and related immunoproteasome disorders. <h3>References</h3> [1] Arima K, et al. <i>PNAS</i>2011;108(36):14914–9. [2] Kawasaki Y, et al. Arthritis Rheum2017;69(2):447–459. [3] Takada S, et al. J Allergy Clin Immunol2018;141(1):339–349. <h3>Acknowledgements</h3> We thank Dr. Fumiko Honda-Ozaki and Ms Madoka Terashima for conducting researdch. We also thank Drs. Nobuo Kanazawa, Akira Niwa, Masakatsu Yanagimachi, Akitsu Hotta and Tatsutoshi Nakahata, and Ms. Haruna Ito for percitipating. Funding was provided by Japan Agency for Medical Research and Development, Tokyo, Japan. <h3>Disclosure of Interest</h3> None declared
THU0567 Testing performance measures identifies gaps in juvenile idiopathic arthritis (JIA) care
Authors: C. Barber, D. Lacaille, L. Lix, K. Kroeker, D.A. Marshall, N. Shiff
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> JIA is the most prevalent type of childhood inflammatory arthritis. Timely diagnosis, treatment and ongoing care by a paediatric rheumatologist are associated with improved outcomes. <h3>Objectives</h3> To test the Arthritis Alliance of Canada's JIA Performance Measures: i) The percentage of patients with new onset JIA with at least one visit to a paediatric rheumatologist in the first year of diagnosis; ii) The percentage of patients with JIA under rheumatology care seen in follow-up by a paediatric rheumatologist at least once per year. <h3>Methods</h3> Validated JIA case ascertainment algorithms were used to identify cases from provincial health administrative databases in Manitoba, Canada in patients&lt;16 years of age with ≥6 months of health insurance coverage in the population registry between 01/04/2005 and 31/03/2015. Cases were identified by either 1 hospitalisation separation with an International Classification of Disease (ICD)−10 code for JIA (M05.X, M06.X, M08.X, M45.X) or ≥2 physician billing claims (ICD-9 codes: 714.x or 720.x) for JIA≥8 weeks apart within 2 years. A 3 year washout period prior to the first code was used to determine the percentage of incident JIA patients with ≥1 visit to a paediatric rheumatologist in the first year. For reporting the percentage of JIA patients seen in yearly follow-up, once a patient is seen at least twice by a paediatric rheumatologist they are considered under rheumatology care. The measure was computed by comparing yearly observed and expected follow-ups. The proportion of patients with gaps in care of &gt;12 and&gt;14 months between consecutive rheumatologist visits was also calculated. As there is no paediatric rheumatologist identifier in Manitoba administrative datasets, a physician was identified as a paediatric rheumatologist if they had ≥40 visits for individuals≤16 years in a year and at least 50% of those visits in a year were JIA. This identified 5 physicians. <h3>Results</h3> 194 incident cases of JIA were diagnosed between 01/04/2008 and 03/31/2015. The median age at diagnosis was 9.1 years (Q1 5.5, Q3 12.8) and 71% were female. Table 1 describes the number of JIA cases who saw a paediatric rheumatologist within a year of diagnosis (between 51% and 81%). Table 2 describes the percentage of patients seen on a yearly basis with no significant changes seen over time (p=0.47). A single gap of &gt;12 months was seen in 52% (n=144) and ≥2 gaps of &gt;12 months were seen in 11% (n=28). One gap of &gt;14 months was seen in 34% of cases, and only 5% had ≥2 gaps&gt;14 months. <h3>Conclusions</h3> Many JIA patients are not seen by a paediatric rheumatologist within a year of diagnosis, and up to half of those followed have at least 1 gap in care of &gt;12 months. Such gaps may lead to a delay in diagnosis, timely treatment and ongoing care that could impact outcomes. <h3>Disclosure of Interest</h3> None declared
SAT0745-HPR Time to diagnosis, but not disease duration, is associated with poor quality of life in spondyloarthritis: results from the asas-comospa study
Authors: M.H. Derakhshan, N. Goodson, J. Packham, R. Sengupta, A. Molto, H. Marzo-Ortega, S. Siebert
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Spondyloarthritis (SpA) is a group of related chronic inflammatory conditions associated with impaired quality of life. <h3>Objectives</h3> To explore the potential associations between both “Time to Diagnosis” and “SpA Disease Duration” and current quality of life in SpA. <h3>Methods</h3> Using ASAS-COMOSPA, a large international cross-sectional study comprising 3984 patients with SpA, we investigated the association between either “Time to Diagnosis” (time from symptom onset to diagnosis) or “SpA Disease Duration (time from symptom onset to study visit)” and current quality of life at the single study visit. Data collected from 5 domains of quality of life in EQ-5D-3L were summarised as an index (ranging from −0.59 to 1.00). In separate models of linear regression, the association between the aforementioned chronology parameters with the quality of life index were investigated before and after adjustments for age, sex, education, HLA-B27, BMI, smoking, alcohol, and medication (NSAIDs, steroids, DMARDs, biologics) history. <h3>Results</h3> Data for 3923 patients (35.1% female; mean age 43.21 (SD: 13.89) years) were available for this analysis. The median (IQR) quality of life index was 0.64 (0.36–0.89) for the entire cohort. In multivariate analysis, “Time to Diagnosis” was significantly associated with poorer quality of life (p=0.005). Other factors and covariates associated with adverse quality of life were higher BMI (p&lt;0.001), smoking (p=0.003), ever use of NSAIDs (p&lt;0.001), ever use of steroids (p&lt;0.001) and ever use of biologics (p=0.002). Factors associated with favourable quality of life were male gender (p&lt;0.001), higher education (p&lt;0.001) and HLA-B27 positivity (p=0.006) (Table). In contrast, “SpA Disease Duration” was not associated with the current quality of life index when corrected for confounders, including age. <h3>Conclusions</h3> In this global cohort of patients with SpA, time to diagnosis but not the duration of SpA appears to be associated with current quality of life, as assessed by the EQ-5D-3L index. Future work should explore geographic variation and whether this association is the same for axial and peripheral SpA disease. <h3>Disclosure of Interest</h3> None declared
SAT0625 Sarcoidosis is associated with an increased risk of gastrointestinal events: a population-based retrospective cohort study 1976–2013
Authors: P. Ungprasert, C.S. Crowson, E.L. Matteson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> An increased risk of gastrointestinal (GI) diseases has been observed in several chronic inflammatory disorders but the risk in patients with sarcoidosis is not known. <h3>Objectives</h3> This study was undertaken to characterise the risk of GI diseases in patients with sarcoidosis. <h3>Methods</h3> A population-based cohort of 345 incident cases of sarcoidosis among Olmsted County, Minnesota residents in 1976–2013 was identified from a comprehensive medical record-linkage system. Diagnosis was confirmed by individual medical record review. A cohort of 345 sex and age-matched comparators was also identified from the same underlying population. Medical records of both groups were reviewed for GI diseases. Cox models adjusted for age, sex and calendar year were used to compare the rate of development of GI diseases between the groups. <h3>Results</h3> GI events occurred in 101 cases and 63 comparators, corresponding to an adjusted hazard ratio (HR) of 1.90 (95% confidence interval [CI] 1.38–2.61). Patients with sarcoidosis had an increased risk for both upper (HR 1.90; 95% CI 1.27–2.83) and lower GI events (HR 1.97; 95% CI 1.27–3.05) relative to comparators. By disease type, patients with sarcoidosis had a significantly elevated risk of upper GI ulcer, upper GI haemorrhage and diverticulitis (<b>table 1</b>). <h3>Conclusions</h3> Patients with sarcoidosis have a higher risk of both upper and lower GI events compared with subjects without sarcoidosis. <h3>Disclosure of Interest</h3> None declared
AB0814 Sodium thiosulfate 10% intralesional to treat calcinosis in patients with systemic sclerosis and dermatomyositis: case series
Authors: A.F. Tonial, M.P.M. Cathcart, T.A.F.G. Santos, P.M. Azevedo, T.L. Skare, P. Martin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Calcinosis is a frequent complication of systemic sclerosis and dermatomyositis, causing local pain, joint mobility reduction, ulcerations, secondary infections and disability. Currently, there is no effective treatment to calcinosis, but the use of topical dressing or intralesional sodium thiosulfate (STS) has showed promising results. <h3>Objectives</h3> To evaluate efficacy of intralesional STS 10% in calcinosis of patients with dermatomyositis and systemic sclerosis. <h3>Methods</h3> Prospective and open-labbed study including dermatomyositis and systemic sclerosis patients with calcinosis. The primary endpoints were: pain relief evaluated through visual analogue scale (VAS) and reduction of major diameters of calcinosis in x-ray. The secondary endpoints were: improvement in the quality of life and function evaluated by SF12 and HAQ respectively. <h3>Results</h3> A total of 10 calcinosis from 7 patients, one with dermatomyositis and 6 with systemic sclerosis were treated. The average dosage of STS per aplication was 9.27 mg at intervals ranging between 15 and 30 days (mean=17.85) between each injection. The number of injections per each calcinosis ranged between 3 and 8 (mean 3.3). All patients reported improvements in pain, however the results were not statistically significant (table 1). There were no reductions in calcionosis diameters, nor improvement of quality of life and function. <h3>Conclusions</h3> Low doses of sodium thiosulfate applied through intralesional injections, in a restrict number of applications and long intervals were not effective to treat calcinosis. <h3>References</h3> [1] Baumgartner-Nielsen J, Olesen AB. Treatment of skin calcification with sodium thiosulfate: a case series. Acta Derm Venereol2016; 96: 257–258. [2] Goossens J, Courbebaisse M, Caudron E, et al. Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: Two cases. Semin Arthritis Rheum. 2017;47(3):451–455. [3] Noureddine L, Landis M, Patel N, et al. Efficacy of sodium thiosulfate for the treatment for calciphylaxis. Clin Nephrol. 2011;75(6):485–90. [4] Smith JP. Intradermal sodium thiosulfate for exophytic calcinosis cutis of connective tissue disease. J Am Acad Dermatol2013; 69:146–7. [5] Bienvenu B. Treatment of subcutaneous calcinosis in systemic disorders. Rev Med Interne. 2014; 35(7):444–52. <h3>Disclosure of Interest</h3> None declared
Conception and Pregnancy Outcomes after Haematopoietic Stem Cell Transplant: A Retrospective Study from the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation
Authors: Nina Salooja, David Michonneau, André Tichelli, Steffie van der Werf, Mahmoud Aljurf, Paul V Browne, Peter Dreger, Kate Hill, Kroger Nicolaus, Myriam Labopin, Maria Teresa Van Lint, Bruno Lioure, Per Ljungman, Johan Maertens, Jakob R. Passweg, Helene Schoemans, Petr Sedlacek, Gérard Socié, Jane Apperley, Peter Bader, Rafael F Duarte, Grzegorz W Basak
Journal: Blood (2018)
Interstitial Lung Disease and Mediastinal Lymph Nodes: A Computed Tomography–based Biomarker beyond Nosological and Etiological Borders?
Authors: Alain Lescoat, Mathieu Lederlin, Alice Ballerie, Nicolas Belhomme, Catherine Cavalin, Patrick Jégo, Stéphane Jouneau
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Prenatal Exposure to Select Phthalates and Phenols and Associations with Fetal and Placental Weight among Male Births in the EDEN Cohort (France)
Authors: Claire Philippat, Barbara Heude, Jérémie Botton, Nadia Alfaidy, Antonia M. Calafat, Rémy Slama
Journal: Environmental Health Perspectives (2019)

Background: The placenta performs crucial physiological functions to ensure normal fetal development. Few epidemiological studies investigated placental weight sensitivity to phthalates and phenols. Objective: Our goal was to explore whether maternal exposure to select phthalates and phenols is associated with changes in placental weight at birth and in placental–to–birth weight ratio (PFR). Methods: Placental weight and birth weight were available for 473 mother–son pairs in the EDEN (Etude des Déterminants pré et postnatals du développement et de la santé de l'Enfant) cohort for whom 9 phenols (4 parabens, 2 dichlorophenols, triclosan, benzophenone-3, bisphenol A) and 11 phthalate metabolites were measured in spot urine samples collected between weeks 23 and 29 of gestation. We used adjusted Elastic Net penalized regression models (ENET) to select biomarkers associated with placental weight, birth weight and PFR. Unpenalized effect estimates were then obtained by fitting linear regression models simultaneously adjusted for the ENET-selected biomarkers and a priori chosen confounders. Results: The multipollutant ENET model for placental weight retained four biomarkers: triclosan and monocarboxy-isononyl phthalate (MCNP), which were negatively associated with placental weight, and benzophenone-3 and the sum of parabens, which were positively associated with this outcome. The ENET model for PFR retained two phthalate metabolites [MCNP and monocarboxy-isooctyl phthalate (MCOP)], which were negatively associated with this outcome. Discussion: The positive association between the sum of parabens and placental weight was consistent with results of a previous study among 49 male births. Our results provide preliminary evidence of possible associations between other compounds such as triclosan, benzophenone-3, MCNP, and MCOP and both placental weight and PFR. These associations were not reported in previous studies and should be seen as hypothesis generating. Studies relying on repeated assessments of exposure in prospective mother–child cohorts are needed to substantiate the plausibility of the hypotheses generated by our results. https://doi.org/10.1289/EHP3523
Improved Relapse-Free Survival and Overall Survival in Patients with High Immune Reconstitution of Gamma Delta T Cells 2 Months after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Lia Minculescu, Hanne Vibeke Marquart, Lars Peter Ryder, Ida Schjødt, Lone Smidstrup Friis, Brian Thomas Kornblit, Søren Lykke Petersen, Niels Smedegaard Andersen, Eva Kannik Hastrup, Anne Fischer-Nielsen, Henrik Sengeloev
Journal: Blood (2018)
SAT0088 Predictive factors for interstitial lung disease progression in patients with rheumatoid arthritis: a role for biological inflammation and disease modified anti rheumatic drugs (DMARDS)
Authors: C. Lucas, S. Jouneau, M. Lederlin, S. Guillot, C. Salliot, L. Joffres, E. Solau-Gervais, M. Herbette, A. Saraux, J.-B. Cren, B. Bouvard, J.-D. Albert, G. Coiffier, P. Guggenbuhl, A. Perdriger
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Interstitial Lung Disease (ILD) related to Rheumatoid Arthritis (RA) is frequent. ILD is associated with an increased mortality in RA patients. Predictive factors for ILD progression are not well studied. <h3>Objectives</h3> In RA patients with an ILD according to CT scan criteria, identify clinical and biological predictive factors for ILD progression. <h3>Methods</h3> It is a retrospective multicentric study. RA patients with ILD confirmed by a first thoracic CT scan (tCT at T0) were included if ILD progression could be studied with a second CT scan (Tx) done at least 6 months after T0. RA patients were classified in two groups after double tCT evaluation on a blind review of data: those with ILD progression (pILD) and those with a stable ILD (sILD). Predictive factors for tCT ILD progression were studied by comparing these two groups. Studied data were ILD pattern, classified into typical UIP (Usual Interstitial Pneumonia) or not typical UIP, RA disease characteristics, biological parameters, and RA treatments, collected for each patient at T0 and Tx. <h3>Results</h3> Thirty-six RA patients with ILD confirmed by tCT were included. During an average follow-up of 3 years, 21 RA patients (58.1%) had ILD progression. Predictive factors for ILD progression a T0 are shown in table 1. In pILD group, we observed a significant higher value of the C Reactive Protein (CRP). A CRP rate superior to 20 mg/L was highly associated to ILD progression (Odds ratio=14.4; IC95%(1.36–15.2); p=0.02). Eight patients were treated at T0 by a DMARD different from Methotrexate (MTX). They all were in pILD group (p=0.01). Thirteen patients were treated with MTX at T0. Eight of them were in sILD group (61.5%) and only 5 patients in pILD group (38.5%). Eight patients continued MTX treatment after ILD diagnosis and for one patient, MTX was introduced between T0 and TX. For these 9 patients exposed to MTX after ILD diagnosis, during 27 months on average, no significant ILD progression was observed. <h3>Conclusions</h3> Factors associated with ILD progression were biological inflammation and exposure to a DMARD different from MTX. Exposure to MTX before or after ILD diagnosis was not associated with ILD worsening during the follow up. <h3>Disclosure of Interest</h3> None declared
Reversal of Chemoresistance in Leukemia Cells Using Synthetic Bisbenzylisoquinoline Derivatives
Authors: Martin Müller, Susanne Gerndt, Anja Arner, Yu-Kai Chao, Linus Schömig, Carina Atzberger, Martin Biel, Franz Bracher, Angelika Vollmar, Vera Binder, Marco Keller, Christian Grimm, Karin Bartel
Journal: Blood (2018)
Expression of neuron specific enolase (NSE) in metastatic melanoma: Implications for progression of disease
Authors: Senthamil Selvan, Robert Dillman, Abner Fowler, Divya Arunachalam, Denysha Carbonell, Mepur Ravindranath
Journal: Cancer Research (2008)

5567   For immunotherapeutic treatment of organ-metastasized melanoma patients, we formulate melanoma cell vaccine from patients own tumor tissues. Antigen profiling is a critical aspect of immunotherapy. In view of well known heterogeneity of human melanoma, neither all tumor cells express all the antigens nor the antigens expressed by all cells are of same density. Very few studies have been undertaken to correlate antigen expression by the tumor cells used in vaccine with therapeutic outcome. Using a semiquantitative immunocytochemistry protocol, we have carried out antigen profiling of the autologous tumor cell vaccine. The following marker antigens were studied: CD20, CD24, CD33, CD34, CD44, CD117, CD133, CD166, ABCG2, Chk1, Chk2, 4-Oct, Muc-18, Neuron Specific Enolase (NSE), and Nestin in 27 cell lines. There are two aspects to these antigen markers. First, their prevalence or absence in the tumor tissue of the patient. Second, their prevalence or absence in the tumor cell vaccine administered to the patient. Both are critical to make correlation of antigen expression with survival. All cell lines have expressed uniformly CD44. Of other antigens, CD20, CD33, CD166, Muc-18, Nestin, and NSE were expressed at varying levels in these cell lines. The rest of the antigens (CD24, CD34, CD117, CD133, ABCG2, Chk1, Chk2, and 4-Oct) were negative in all cell lines. Expression of Nestin was seen in 26/27 cell lines with >25% cells in 21 and  25% cells in 24 and   25% cells in 14 cell lines whereas