tbuckley/cabot-search huggingface dataset:
OP0319 High sensitivity cardiac troponin T is a biomarker for atherosclerosis in systemic lupus erythematous patients: a cross-sectional controlled study
Authors: G Divard, R Abbas, C Chenevier-Gobeaux, B Escoubet, M-P Chauveheid, A Dossier, M Dehoux, T Papo, K Sacre
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Cardiovascular disease (CVD) is the main cause of death in systemic lupus erythematous (SLE) patients. Framingham score underestimates the risk for CVD in this population. <h3>Objectives</h3> Our study aimed to determine whether serum High Sensitivity Cardiac Troponin T (HS-cTnT) helps to identify SLE patients at risk for CVD. <h3>Methods</h3> Presence of carotid plaques was prospectively assessed by ultrasound in 63 consecutive SLE patients asymptomatic for CVD and 18 controls. Serum HS-cTnT concentration was measured using the electrochemiluminescence method. Factors associated with carotid plaques were identified and multivariate analysis was performed <h3>Results</h3> Framingham score was low in both SLE patients (2.1±3.8%) and controls (2.1±2.9%). Nevertheless, 23 (36.5%) SLE patients, but only 2 (11.1%) controls (p=0.039), had carotid plaque detected by vascular ultrasound. In the multivariate analysis, only age (p=0.006) and SLE status (p=0.017) were independently associated with carotid plaques. Serum HS-cTnT concentration was detectable (i.e. &gt;3 ng/L) in 37 (58.7%) SLE patients and 6 (33.3%) controls (p=0.057). Interestingly, 87% of SLE patients with carotid plaques, but only 42.5% in SLE patients without plaques (p&lt;0.001), had a detectable HS-cTnT. Conversely, 54.5% SLE patients with a detectable HS-cTnT, but only 11.5% with an undetectable HS-cTnT (p&lt;0.001), had a carotid plaque. In the multivariate analysis, only BMI (p=0.006) and HS-cTnT (p=0.033) were statistically associated with carotid plaques in SLE patients. Overall, the risk of having a carotid plaque was increased by 8 (OR [95% CI]: 8.03 [1.41–74.73]) in SLE patients in whom HS-cTnT was detectable in serum. <h3>Conclusions</h3> Detectable HS-cTnT concentration is independently associated with subclinical atherosclerosis in asymptomatic SLE patients at apparent low risk for CVD according to traditional risk factors. These results raise the possibility that this easily obtained biomarker is useful for more rigorous risk stratification and primary prevention of CVD in SLE patients. <h3>Disclosure of Interest</h3> None declared
FRI0402 Onset clinical involvement as prognostic factor in systemic sclerosis (SSC)
Authors: M Fernández Pestaña, M Rubio Rivas, C Tolosa Vilella, A Guillén del Castillo, D Argüelles Colunga, L Trapiella Martinez, V Fonollosa Pla, CP Simeόn Aznar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In most patients with SSc, the onset is in the form of Raynaud9s phenomenon (RP), but in a few is in the form of visceral or musculoskeletal involvement or skin sclerosis. Several risk factors are related to poor outcome in patients with SSc, but never before has the mode of onset been described as one of them. <h3>Objectives</h3> To asses the mode of onset as prognostic factor in patients with SSc. <h3>Methods</h3> A retrospective and multicentre cohort study including 1625 patients with SSc, based on the National Spanish Scleroderma Registry (RESCLE) which includes 28 referral centres. RP, puffy hands, arthralgia/arthritis, skin sclerosis, intersititial lung disease (ILD), pulmonary arterial hypertension (PAH) and esophageal hipomotility where included as clinical modes of onset. <h3>Results</h3> The cohort was split up in two groups: 1342 patients (83%) presented as RP and 283 (17%) presented as non-RP (see graphic below) Non-RP patients where younger at onset of disease (44.7±16.5 vs 49±15.6 years, p&lt;0.001), showed higher percentage of diffuse subtipe (36% vs 19%, p&lt;0.001), developed more visceral involvement during the course of the illness and where more frequently anti-RNAp III positive (29 vs 10%, p&lt;0.001). Overall mortality was 16% in patients presented as RP vs 23% in non-RP patients (p=0.003). Few differences where noted among causes of death related to SSc, but the higher mortality was observed in RP group due to PAH (19% vs 8.1%, p=0.05) and due to ILD in non-RP group (24% vs 8.3%, p=0.002). Survival of patients with RP at onset was better at anytime than those with a non-RP onset: 0.97 vs. 0.89 at 5 years, 0.93 vs. 0.82 at 10 years, 0.83 vs. 0.63 at 20 years and 0.71 vs. 0.51 at 30 years from onset (p&lt;0.001). <h3>Conclusions</h3> The mode of onset can be considered as independent prognostic factor, and specifically non-RP onset can be considered as a risk factor related to poorer outcome and RP onset and arthralgias can be considered as protector factors. <h3>Disclosure of Interest</h3> None declared
The multi-dimensional μLC-MALDI-TOF/MS differential proteome analysis revealed novel cancer biomarkers for hepatoma
Authors: Kazuhiko Uchida, Kohj Meno, Hirotaka Fujimoto, Tetsuo Tanigawa, Eiji Yamaguchi, Yasuhiko Takeda, Reiko Takano, Katsuya Shiraki, Shinji Uemoto, Takuya Katagiri
Journal: Cancer Research (2006)

2869  Hepatocellular carcinoma (HCC) is one of the most fatal cancers with a high incidence in many countries. Hepatitis C virus (HCV) is the most clearly established risk factor for HCC. HCV carriers proceed to chronic hepatitis (CH), to liver cirrhosis (LC), and to HCC after incubation periods. Molecular biomarkers are biological molecules that are indicators of physiologic state and also of change during a carcinogenesis. Mass spectrometry-based protein/peptide profiling and differentially detected proteins in serum or plasma have been identified as diagnostic biomarkers. However, most of them are from degradation fragments of major plasma proteins and few cellular proteins from cancer cells have been reported. To identify sensitive and accurate diagnostic biomarkers, differential plasma proteome profiling which enable us to detect tiny amount of cancer-cell derived protein/peptide in blood. Here we established comprehensive and sensitive analytical platform using automated multi-dimensional μLC-MALDI-TOF/MS and identified several peptide biomarkers which discriminate liver caner and non-cancer disease. Serum samples were pretreated and separated by two-dimensional HPLC; strong cation exchange (SCX) for the 1st dimension and reverse phase (RP) for the 2nd dimension. The separated samples were spotted onto three MALDI targets automatically. More than 10,000 fractions were analyzed automatically by MALDI-TOF MS in reflector mode. We identified angiotensin II as a spike in processed serum at 1 nM concentration. Huge data of the peptide expression profiles generated from mass spectrometry were analyzed on the differential analysis tools originally developed by us. Analysis of human serum from liver cancer and non-cancer patients revealed several differentially-expressed proteins that indicate ROC value >0.8. Without re-purification, sequential analysis by MSn on MALDI-QIT-TOF MS revealed post-translational modification of some biomarkers. We identified and validated nine potential biomarkers specific for liver cancer. These novel biomarkers may improve early detection of liver cancer and lead to correct treatment of liver disease.
A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci
Authors: Diana Chang, Mike A Nalls, Ingileif B Hallgrímsdóttir, Julie Hunkapiller, Marcel van der Brug, Fang Cai, Geoffrey A Kerchner, Gai Ayalon, Baris Bingol, Morgan Sheng, David Hinds, Timothy W Behrens, Andrew B Singleton, Tushar R Bhangale, Robert R Graham
Journal: Nature Genetics (2017)
AB0567 The long term health related quality of life (HRQOL) impact on giant cell arthritis (GCA) patient
Authors: H Horiuchi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Health related quality of life (HRQOL) of Giant cell Arthritis (GCA) patients is improtant because it adds depth to our understanding of how a disease and its treatments affect them. Though only one previous study has addressed the short term impact of GCA on HRQOL, the long term impact has not fully been investigated. <h3>Objectives</h3> The aim of our study is to assess the long term HRQOL outcomes of GCA patients using the Japanese version of EuroQol 5 Dimention (EQ-5D). <h3>Methods</h3> 40 GCA patients who admitted to our hospital from November 2004 to June 2014 were enrolled. All patients were received prednisolone over 2 years. Patients who had lost their eyesight were excluded because vision concern for HRQOL nor it is difficult to mesure by using EQ-5D. This is a retrospective study and deta were collected by telephone interview. Patients evluated their health status using five dimensions. The EQ-5D score were calculated based on the Japanese version of the value set. Primary outcome is the mortality rate and the norm of EQ-5D score. As a secondary analysis, we classified the patients as follows and compare the mortality rate and EQ-5D score between two groups. Group 1: GCA patients who received prednisolone over 5 years. Group 2: GCA patients who received prdnisolone less than 5 years. <h3>Results</h3> There were 16 male (40%) and 24 female (60%). The median age was 83.5 (95% CI 79.24–87.76). The mortality rate was 37.5% (15 patients). Kaplan-Meier curve is shown in Figure1. The median EQ-5D score was 0.746 (95% confidence interval [CI] 0.852–0.640) and it is lower than Japanese norm (0.853 in male and 0.808 in female). In the secondary analysis, the mortality rate was 56.0% (14 patients) in Group1 and 6.6% (1 patient) in Group2. It was significantly higher in Group 1 (<i>P</i>&lt;0.05). The median EQ-5D score was 0.764 (95% CI 0.579–0.870) in Group1 versus 0.768 (95% CI 0.621–0.915) in Group2. There was no statistically significant difference between them (<i>P</i>=0.813). <h3>Conclusions</h3> This study focused on GCA patients with prednisolone therapy over 2 years. It showed that EQ-5D was decreased compared with the Japanese norm but it didn9t clearly decrease after 2 years of treatment. These findings suggest the value of measuring health status in GCA patients by EQ-5D at least first 2 years of treatment, because it would allow comprehensive evaluation of the patient9s health condition and add another dimension to the subjective symptoms and laboratory data. <h3>References</h3> Arthritis and Rheumatism Vol.49,No6, December 15,2003,pp819–825. J Neuroophthalmol. 2001 Dec;21(4):266–73. <h3>Disclosure of Interest</h3> None declared
OP0236 Benefit and safety of antithrombotic treatment in 264 pregnancies in patients with antiphospholipid syndrome
Authors: CM Yelnik, M Lambert, E Drumez, V Le Guern, J-L Bacri, M Guerra, CA Laskin, W Branch, LR Sammaritano, N Morel, G Guettrot-Imbert, D Launay, E Hachulla, P-Y Hatron, JE Salmon, N Costedoat-Chalumeau
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The management of pregnancy in patients with antiphospholipid syndrome (APS) with aspirin and heparin is based on empiric recommendations. <h3>Objectives</h3> Our study aimed to evaluate the outcomes of treated patients with thrombotic and obstetric APS and the safety of antithrombotic treatments prescribed during pregnancy. <h3>Methods</h3> Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow up data until 6 weeks post-partum. Data were collected prospectively (PROMISSE study) and retrospectively (four French centers). Adverse pregnancy outcomes (APOs) were defined by fetal death or neonatal death; pre-term delivery before 36 WG due to preeclampsia or placental insufficiency; or small for gestational-age (SGA; &lt;5th percentile). Major bleeding was defined as blood loss greater than 500mL and/or requiring surgery or transfusion. <h3>Results</h3> 264 pregnancies (87 collected prospectively) in 204 patients were included (46% with a history of thrombosis, and 23% with associated systemic lupus erythematosus). During pregnancy, treatment included heparin (n=253; 96%) and low-dose aspirin (n=223; 84%). The live birth rate was 86%. APOs occurred in 32%, mostly during the 2nd trimester: fetal deaths 11%, SGA 11%, pre-term delivery before 36 WG due to preeclampsia or placental insufficiency 17%. Thirteen maternal thrombotic events occurred in 12 (4.5%) pregnancies. Forty-six maternal hemorrhagic events occurred in 40 (15%) pregnancies (30 events in the post-partum period). Major bleeding was reported in only 6 pregnancies (2.3%) and occurred only after delivery. Except for two events, post-partum hemorrhage occurred in the early post-partum before hospital discharge. No maternal death was observed. Aspirin therapy during pregnancy was the only independent factor associated with a lower risk of APOs (odds ratio: 0.34; 95% CI: 0.15 – 0.78; p=0.01) in multivariate analysis. Neither heparin or aspirin alone, nor combined therapy increased the risk of hemorrhage. In the retrospective cohort, emergency caesarian section was the only factor associated with hemorrhagic events during the study period (53% hemorrhages in patients who underwent emergency caesarian compared to 18%, p=0.005). Independent risk factors for APOs were elevated body mass index and the presence of lupus anticoagulant. <h3>Conclusions</h3> We report a high level of obstetrical complications in conventionally-treated APS pregnancies, and a beneficial effect of addition of aspirin to prevent obstetrical morbidity. Moreover, heparin and aspirin were well tolerated and did not increase risk of hemorrhage. <h3>Disclosure of Interest</h3> None declared
ワクチンナノキャリア:結合細胞内経路および細胞生体内分布CD4対CD8T細胞応答を制御する【Powered by NICT】
Authors: Rincon-Restrepo Marcela, Mayer Aaron, Hauert Sylvie, K Bonner Daniel, A Phelps Edward, A Hubbell Jeffrey, A Swartz Melody, Hirosue Sachiko
Journal: Biomaterials (2017)
Berunda Polypeptides: Multi-Headed Fusion Proteins Promote Subcutaneous Administration of Rapamycin to Breast Cancer <i>In Vivo</i>
Authors: Jugal P. Dhandhukia, Zhe Li, Santosh Peddi, Shruti Kakan, Arjun Mehta, David Tyrpak, Jordan Despanie, J. Andrew MacKay
Journal: Theranostics (2017)

Recombinant Elastin-Like Polypeptides (ELPs) serve as attractive scaffolds for nanoformulations because they can be charge-neutral, water soluble, high molecular weight, monodisperse, biodegradable, and decorated with functional proteins. We recently reported that fusion of the FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) reduces rapamycin (Rapa) toxicity and enables intravenous (IV) therapy in both a xenograft breast cancer model and a murine autoimmune disease model. Rapa has poor solubility, which leads to variable oral bioavailability or drug precipitation following parenteral administration. While IV administration is routine during chemotherapy, cytostatic molecules like Rapa would require repeat administrations in clinical settings. To optimize FKBP/Rapa for subcutaneous (SC) administration, this manuscript expands upon first-generation FSI nanoparticles (Rh ~ 25 nm) and compares them with two second-generation carriers (FA and FAF) that: i) do not self-assemble; ii) retain a hydrodynamic radius (Rh ~ 7 nm) above the renal filtration cutoff; iii) increase tumor accumulation; and iv) have either one (FA) or two (FAF) drug-binding FKBP domains per ELP protein. Methods: The carriers were compared and evaluated for temperature-concentration phase behavior by UV-Vis spectrophotometry; equilibrium binding and thermodynamics by Isothermal Titration Calorimetry; drug retention and formulation stability by Dialysis and Dynamic Light Scattering; in vitro efficacy using a cell proliferation assay; in vivo efficacy in human MDA-MB-468 orthotopic breast cancer xenografts; downstream target inhibition using western blot; tissue histopathology; and bio-distribution via optical imaging in the orthotopic xenograft mouse model. Results: Named after the two-headed bird in Hindu mythology, the 'Berunda polypeptide' FAF with molecular weight of 97 kDa and particle size, Rh ~ 7 nm demonstrated polypeptide conformation of a soluble hydrated coiled polymer, retained formulation stability for one month post Rapa loading, eliminated toxicity observed with free Rapa after SC administration, suppressed tumor growth, decreased phosphorylation of a downstream target, and increased tumor accumulation in orthotopic breast tumor xenografts. Conclusion: This comprehensive manuscript demonstrates the versatility of recombinant protein-polymers to investigate drug carrier architectures. Furthermore, their facilitation of SC administration of poorly soluble drugs, like Rapa, may enable chronic self-administration in patients.
Differentiation of Malignant Thrombus From Bland Thrombus of the Portal Vein in Patient With Hepatocellular Carcinoma on 18F-FDG PET CT
Authors: Krishan Kant Agarwal, Dipalkumar Shah, Neha Shah, Manas Mayank
Journal: Clinical Nuclear Medicine (2017)

Hepatocellular carcinoma carries a high risk of invasion of the portal vein. Neoplastic and bland portal vein thrombi discrimination is of great clinical significance for determining the therapeutic approach, predicting survival, and assessing candidates for liver transplantation. F-FDG PET/CT may be helpful in discriminating between malignant and portal vein thrombi. We present the case of a 61-year old man who presented with hepatocellular carcinoma with portal vein involvement. F-FDG PET/CT has a role in differentiating malignant from benign portal vein thrombosis.
THU0565 Macrophage activation syndrome in adults with inflammatory rheumatic diseases
Authors: M Olejárová, K Jarošová
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Macrophage activation syndrome (MAS) is a rare hyperinflammatory condition characterised by macrophage activation and infiltration resulting in a multi organ damage. MAS is considered to be a type of secondary hemophagocytic lymphohistiocytosis. It is a life threatening complication of various autoimmune or autoinflammatory rheumatic diseases, particularly systemic juvenile idiopathic arthritis (sJIA). Clinical manifestations include hepatosplenomegaly, increase of liver function tests, pancytopeny, neurolological manifestations etc. High doses of glucocorticosteroids (GC), cyclosporine A (CyA) and etoposide are a treatments of choice. In refractory cases biologicals may be an option, too. <h3>Objectives</h3> To point out this very rare but severe complication may occur also in adult patients with rheumatic diseases. <h3>Methods</h3> We report 4 successfully treated cases of adult MAS in rheumatic patients seen in our clinic during the years 2009 – 2016. A review of the literature regarding the efficacy of biologics in MAS treatment is also presented. <h3>Results</h3> We have observed four patients with MAS, two with adult onset Still disease (AOSD), one with rheumatoid arthritis (RA) and one with sJIA. All of the patients were young (20 -33 years, mean age 27,0±5,61 years) with the duration of the primary disease ranging from 9 months to 11 years (mean 4,18±4,01 years). Three patients were in remission of the primary diseases prior to MAS manifestation, only in the last and most severe patient (AOSD) the activity of the underlying disease was not controlled. A demographic and clinical characteristic of the patients is summarized in the table. All 4 patients were successfully treated, one with high doses of glucocorticosteroids (GC), two with combination GC plus CyA. The last and most severe one had MAS refractory to the combination GC + CyA and must have been added biological therapy (tocilizumab). We reviewed also another cases of MAS treated with biologics which have been published. <h3>Conclusions</h3> Our cases illustrate that MAS may develop also in adult patient with various rheumatic diseases (JIA, AOSD, RA) despite the low activity or remission. It occurs particularly in younger subjects. As the MAS symptoms may overlap with the symptoms of the primary disease (JIA, AODS) the diagnosis may be difficult. MAS must be suspected in inflammatory rheumatic diseases patients with sudden increase of CRP, extreme increase of ferritin, liver function tests and decrease of platelets. An immediate treatment with GC, CyA and etoposide is essential; biologicals (anakinra, canakinumab or tocilizumab) may be benefitial in refractory cases. <h3>Acknowledgements</h3> Supported by MHCR Research project 00000023728. <h3>Disclosure of Interest</h3> None declared
SAT0287 TH1, TH2 and TH17 lymphoid subpopulations in primary antiphospholipid syndrome
Authors: G Medina, OI Florez-Durante, L Montiel Cervantes, R Molina-Aguilar, E Reyes-Maldonado, LJ Jara
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Primary antiphospholipid antibody syndrome (PAPS) is characterized by thrombosis at different levels and maternal fetal complications in the presence of antiphospholipid antibodies (aPL). Lymphoid subpopulations and cellular immune responses have not been fully studied. <h3>Objectives</h3> To analyze the lymphoid subpopulations, Th1, Th2 and Th17 immune response in patients with PAPS and long term evolution. <h3>Methods</h3> Patients with PAPS,&gt;18 years of age, of both sexes and a group of healthy blood donors matched for age and sex were included. All patients were receiving oral anticoagulants (Coumadin type). No patient had a recent episode of thrombosis or other manifestation of APS at the time of the study. Peripheral blood was obtained and lymphoid subpopulations were determined by flow cytometry in order to identified with specific immunological markers for Treg cells: CD4+/CD25+/FoxP3+ and CD8+/CD25+/FoxP3+. The dendritic cells analyzed were: Type 1: Lin1- HLA-DR+/CD11c+; Type 2: Lin-HLA-DR+/CD123+; B lymphocytes with antiCD19-APC; Monocytes with anti-CD14-PE; NK: CD3-/CD16+56+ and NKT: CD3+/CD16+56+ lymphocytes. Th1 cells were identified by IFN-g<sup>+</sup> positivity; Th2: positivity for IL-4+; Th17: positivity for IL-17+. Parametric statistics and Mann-Whitney U-test were used. <h3>Results</h3> A total of 39 patients with PAPS were included, age: 51.9±12.8, evolution time: 12.8±8.9 years and 35 healthy controls. In patients with PAPS there was a decrease in the total CD8 count (p&lt;0.05) in iNKT (p&lt;0.005), DC1 (p&lt;0.005) and DC2 (p&lt;0.0005) cells compared to the control group (Table 1).We found significant decrease in Th1, Th2 and Th17 cytokines basal and after activation compared to healthy controls. <h3>Conclusions</h3> This study shows profound alterations in innate and adaptive immunity in patients with long-term PAPS, characterized by a decrease in certain lymphocyte subpopulations, with consequent functional alteration. These abnormalities can become new therapeutic targets in order to restore immune imbalance. Our findings may explain in part, the development of thrombosis and other complications, despite treatment with oral anticoagulants in PAPS patients with long term disease evolution. <h3>References</h3> Dal Ben ER, do Prado CH, Baptista TS, Bauer ME, Staub HL. Decreased levels of circulating CD4+CD25+Foxp3+regulatory T cells in patients with primary antiphospholipid syndrome. J Clin Immunol 2013; 33: 876–879. Xiao J, Zhu F, Liu X, Xiong J.Th1/Th2/Th17/Treg expression in cultured PBMCs with antiphospholipid antibodies.Mol Med Rep. 2012;6(5):1035–9. Jakiela B, Iwaniec T, Plutecka H, Celinska-Lowenhoff M, Dziedzina S, Musial J. Signs of impaired immunoregulation and enhanced effector T-cell responses in the primary antiphospholipid syndrome. Lupus. 2016; 25(4):389–98. <h3>Disclosure of Interest</h3> None declared