tbuckley/cabot-search huggingface dataset:
AB0099 COCULTURE OF SYNOVIAL MEMBRANE AND CARTILAGE: A POTENTIAL HUMAN EX VIVO CARTILAGE DEGRADATION MODEL
Authors: Johanna Mucke, Victoria Warzynski, Ellen Bleck, Thomas Pauly, Tim Claßen, Matthias Schneider, Stefan Vordenbäumen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cartilage degradation is a hallmark in both osteoarthritis (OA) and rheumatoid arthritis (RA). Ex vivo cartilage models offer the potential to study disease processes but are surprisingly rarely used. <h3>Objectives</h3> Here we investigate the effect of synovial tissue and stimulation with TNF-α on cartilage degradation in a physiologically relevant coculture-model of synovial membrane and cartilage. <h3>Methods</h3> Cartilage and synovial membrane were collected from patients with RA and OA who underwent joint replacement. Cartilage was cultivated either alone or with synovial membrane in medium with or without TNFα as a stimulant for up to 28 days. The explants were harvested at different time points and Safranin-O-staining was performed to visualize proteoglycan (PG) content. A scoring system from 0 (no PG content) to 3 (high PG content) was applied as a semi-quantitative measure for evaluation. Linear mixed modeling adjusted for gender and age was performed to identify factors influencing PG content. <h3>Results</h3> Samples of 18 patients (9 OA, 9 RA) were collected. Factors associated with proteoglycan loss in cartilage were the time in culture (p=0.02), stimulation with TNF-α (p=0.0007) and coculture with synovial membrane (p=0.00002) in univariate analysis with TNF-α (p=0.0009) and coculture (p=0.001) maintaining the level of significance in multivariate analysis. (Figure 1) <h3>Conclusion</h3> Exposure to synovial tissue and TNF stimulation drive cartilage proteoglycan loss in an ex vivo cartilage degradation model. This model may prospectively serve to investigate pathophysiologic pathways of cartilage degradation in both OA and RA. <h3>References</h3> None <h3>Disclosure of Interests</h3> Johanna Mucke: None declared, Victoria Warzynski: None declared, Ellen Bleck: None declared, Thomas Pauly: None declared, Tim Claßen: None declared, Matthias Schneider Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Speakers bureau: Chugai, Stefan Vordenbäumen: None declared
A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens
Authors: Huey‐Jy Huang, Mirela Curin, Srinita Banerjee, Kuan‐Wei Chen, Tetiana Garmatiuk, Yvonne Resch‐Marat, Claudia Carvalho‐Queiroz, Katharina Blatt, Guro Gafvelin, Hans Grönlund, Peter Valent, Raffaela Campana, Margarete Focke‐Tejkl, Rudolf Valenta, Susanne Vrtala
Journal: Allergy (2019)

Abstract Background In the house dust mite (HDM) Dermatophagoides pteronyssinus, Der p 1, 2, 5, 7, 21, and 23 have been identified as the most important allergens. The aim of this study was to define hypoallergenic peptides derived from the sequences of the six allergens and to use the peptides and the complete allergens to study antibody, T cell, and cytokine responses in sensitized and nonsensitized subjects. Methods IgE reactivity of HDM‐allergic and non‐HDM‐sensitized individuals to 15 HDM allergens was established using ImmunoCAP ISAC technology. Thirty‐three peptides covering the sequences of the six HDM allergens were synthesized. Allergens and peptides were tested for IgE and IgG reactivity by ELISA and ImmunoCAP, respectively. Allergenic activity was determined by basophil activation. CD4+ T cell and cytokine responses were determined in PBMC cultures by CFSE dilution and Luminex technology, respectively. Results House dust mite allergics showed IgE reactivity only to complete allergens, whereas 31 of the 33 peptides lacked relevant IgE reactivity and allergenic activity. IgG antibodies of HDM‐allergic and nonsensitized subjects were directed against peptide epitopes and higher allergen‐specific IgG levels were found in HDM allergics. PBMC from HDM‐allergics produced higher levels of IL‐5 whereas non‐HDM‐sensitized individuals mounted higher levels of IFN‐gamma, IL‐17, pro‐inflammatory cytokines, and IL‐10. Conclusion IgG antibodies in HDM‐allergic patients recognize peptide epitopes which are different from the epitopes recognized by IgE. This may explain why naturally occurring allergen‐specific IgG antibodies do not protect against IgE‐mediated allergic inflammation. A mix of hypoallergenic peptides containing T cell epitopes of the most important HDM allergens was identified.
Abstract 13248: Insulin Resistance as a Predictor of Coronary Artery Calcification Progression
Authors: KiChul Sung, EunSun Cheong, Jong Yong Lee, Sung Ho Lee
Journal: Circulation (2015)

Introduction: Obesity, nonalcoholic fatty liver disease (NAFLD) and insulin resistance (IR) may coexist, but it is uncertain whether these conditions contribute independently to atherosclerosis. We tested whether fatty liver, IR and obesity increase coronary artery calcium [CAC] score, a marker of atherosclerosis, independently to cardiovascular risk factors and cardiovascular disease (CVD). Methods: Data were analyzed from a South Korean occupational cohort of 2244 people who all received abdominal ultrasound measurements of fatty liver and non-enhanced coronary computed tomography for CAC score at baseline and follow up. IR was defined by homeostasis model assessment of IR (HOMA-IR) ≥75th percentile. Odds ratios (ORs) (95% CIs) for the presence of a CAC score &gt;0 were estimated using logistic regression. Results: There were 621 people with CAC score progression. Traditional risk factor, type 2 diabetes and hypertension were independently associated with CAC progression (OR for DM 1.86 [1.17-2.95]; OR for HTN 1.43[1.04-1.96]). HOMA-IR (OR: Q4 vs Q1 1.73 [1.07-2.78]) was associated with CAC progression independently of all metabolic syndrome features, conventional cardiovascular risk factors, and prior evidence of DM and HTN. Smoking, educational status, excise frequency were not associated with CAC progression. Synergic effect had occurred with insulin resistance and obesity (OR 3.10, [1.10-8.74]) and also with obesity and fatty liver (OR 1.61, [1.03-2.53]) after adjustment of various confounding factors including age, sex, alcohol consumption, smoking status, excise frequency, degree of education, DM, HTN. The combination of presence of IR, fatty liver and obesity was associated with CAC progression (OR 3.15, [2.10-4.73]) with adjustment of age and sex. Although the association was attenuated, the combination still showed significant association after adjustment of various confounding factors (OR 2.69 [1.69-4.27]). Conclusions: The clustering of NAFLD, obesity and IR, is common and markedly increases the odds of CAC progression, and IR also have effects independently of each other and of confounding factors. The data suggest that treatment for each factor is needed to decrease progression of atherosclerosis.
Gold nanoparticles that target degraded elastin improve imaging and rupture prediction in an AngII mediated mouse model of abdominal aortic aneurysm
Authors: Xiaoying Wang, Brooks A Lane, John F Eberth, Susan M. Lessner, Naren R. Vyavahare
Journal: Theranostics (2019)

Background: Abdominal aortic aneurysms (AAA) are characterized by a progressive disruption and weakening of the extracellular matrix (ECM) leading to dilation of the aorta which can be fatal if not treated.Current diagnostic imaging modalities provides little insight on the varying degree of ECM degeneration that precedes rupture in AAAs.Targeted delivery of contrast agents such as gold nanoparticles (GNPs) that bind to degraded matrix could prove useful when combined with computed tomography (CT) to provide a non-invasive surrogate marker of AAA rupture potential.Methods: AAAs were induced by chronic infusion of angiotensin II (AngII) into low density-lipoprotein receptor-deficient (LDLr -/-) mice in combination with a high-fat diet.Abdominal ultrasound was used to monitor disease progression and to assess the circumferential strain throughout the cardiac cycle.At six weeks, GNPs conjugated with an elastin antibody (EL-GNP) were injected retro-orbitally.Mice were euthanized 24 hours after EL-GNP injection, and aortas were explanted and scanned ex-vivo with a micro-CT system.Histological assessment and 3D models of the aneurysms with micro-CT were used to determine the EL-GNPs distribution.Isolated vessel burst pressure testing was performed on each aneurysmal aorta to quantify rupture strength and to assess rupture location.Results: Aneurysms were found along the suprarenal aorta in AngII infused mice.Darkfield microscopy indicated EL-GNPs accumulation around the site of degraded elastin while avoiding the healthy and intact elastin fibers.Using nonlinear regression, the micro-CT signal intensity of EL-GNPs along the suprarenal aortas correlated strongly with burst pressures (R 2 =0.9415) but not the dilation as assessed by ultrasound measurements.Conclusions: Using an established mouse model of AAA, we successfully demonstrated in vivo targeting of EL-GNPs to damaged aortic elastin and correlated micro-CT-based signal intensities with burst pressures.Thus, we show that this novel targeting technique can be used as a diagnostic tool to predict the degree of elastin damage and therefore rupture potential in AAAs better than the extent of dilation.
A Patient With Abnormal Abdominal CT Scan Findings
Authors: Joseph M. Vitello, Dominic J. Vitello, Myriam Bermudez-Allende
Journal: JAMA (2019)

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THU0583 EXPERIENCE OF ANAKINRA AND CANAKINUMAB IN PATIENTS WITH COLCHICINE-RESISTANT FAMILIAL MEDITERRANEAN FEVER AND COMPLICATED WITH AMYLOIDOSIS
Authors: Ali Şahin, Mehmet Emin Derin, Fatih Albayrak, Burak Karakaş
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Familial Mediterranean Fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation (1). The goal of FMF treatment is to prevent the attacks and to minimize subclinical inflammation between attacks, and in attacks-free period. Colchicine is a major drug that sine qua non in the treatment of FMF. However, anti-interleukin-1 agents are recommended in colchicine resistant and/or intolerant FMF patients (2). <h3>Objectives:</h3> The aim of this study is to evaluate the efficacy of anti-interleukin-1 (anti-IL-1) agents in 54 FMF patients with resistant/intolareted to colchicine or complicated with amyloidosis. <h3>Methods:</h3> Between January 2014 and December 2018, fifty four patients who were diagnosed as FMF according to the criteria of Tel-Hashomer that following-up at Sivas Cumhuriyet University Medical Faculty, Rheumatology-Internal Medicine Department were included in to the study. <h3>Results:</h3> 25 (46.3%) male and 29 (53.7%) female were included in the study. The median age of the patients was 29 (min:17-max: 60) years and the median age at diagnosis was 18 (min: 3-max: 46) years. Anakinra was used in 34 (63%) FMF patients (100 mg/day), and canakinumab was used in 20 (37%) patients (150mg/8weeks). 37 cases were resistant to colchicine, 8 were intolerant to colchicine, 9 (20%) cases were comlicated with amyloidosis. 8 patients had renal transplantation. MEFV gene mutations are shown in Table 1. Median duration of anti-IL-1 agent use was 12 months (min:2-max40). 5 patients were resistant to anakinra, 4 patients had side effects which anakinra related. After a median follow up 12 months overall clinical response was%95 (frequency of attacks &lt;1/6months). Median proteinuria decreased from 3850 mg/day to median 1600 mg/day (p= 0.04) (Table 2). IL-6 treatment was started in 3 patients because of ineffectiveness of canakinumab. One pregnant patient was followed up with anakinra during pregnancy and there were no problems. <h3>Conclusion:</h3> Anti-interleukin-1 agents can be used effectively and safely in the treatment of FMF patients. These agents are especially effective in the treatment of proteinuria due to amyloidosis. Large and long-lasting follow-up studies are needed to evaluate long-term effects of these drugs. <h3>References:</h3> [1] Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. 2019Jan24. pii: S0755-4982(18)30486-X. doi: 10.1016/j.lpm.2018.08.014. [Epub ahead of print]. [2] Seza Özen ve ark. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016Apr;75(4):644-51. <h3>Disclosure of Interests:</h3> None declared
Abstract 221: Use of Statins in Patients with Coronary Artery Aneurysms: A Pilot Study from the North American Kawasaki Disease Registry
Authors: Michael Khoury, Michael A Portman, Cedric Manlhiot, Anne Fournier, Rejane F Dillenburg, Adrian B Dancea, Claudia Renaud, Steven C Greenway, Shelby Kutty, Emilie Beaulieu, Brian W McCrindle
Journal: Circulation (2015)

Background: Statins have been considered as therapy for children with coronary artery aneurysms (CAA) after Kawasaki disease (KD), due to potential beneficial pleiotropic effects which might influence chronic vascular processes and inflammation. Methods: The North American Kawasaki Disease Registry was queried to identify patients who have received statins in the first 6 months following the convalescent phase of KD. Each identified patient was matched by age, gender and CAA z score to 3 patients who were statin-naïve (controls). Linear regression models adjusted for repeated measures and maximum coronary involvement were used to determine an association of statin use with longitudinal changes in coronary artery diameter z-score. Kaplan-Meier analysis was used to compare freedom from angiographically-confirmed stenosis or interventions. Results: Of 29 patients with KD and CAA (maximum coronary artery z-score &gt;10) who received statins at any time (of n=621, 5%), 10 (9 males) patients were started within 6 months of the acute KD episode. The mean age at KD was 6.3±3.4 years (5.4±3.5 for controls, p=0.57). Mean maximum CAA z-score was 36±14 (vs. 29±16, p=0.20); 90% of statin patients and 87% of matched controls had CAAs in 3 or more branches. Linear regression analysis of 442 serial echocardiograms showed that maximum CAA z-score decreased by -1.5 (95%CI: -2.7; -0.4) SD/year (p=0.008) for control patients compared to -2.9 (95%CI: -4.4; -1.4) SD/year (p&lt;0.001) for statin treated patients. The difference between the rate of change of CAA z-score for statin vs. control patients did not reach statistical significance (controls vs. statins: +1.4 SD/year, 95%CI: -0.6; +3.4, p=0.18). n=7 patients (3 on statin, 4 controls) developed stenosis or had revascularization, with no significant difference between groups (HR for statin group: 2.2 (0.4-11.4), p=0.41). Conclusions: This underpowered pilot study suggests that equipoise likely exists with regards to statin therapy in children with KD and CAA, and that a formal registry-nested trial might be considered.
THU0295 POLYMYALGIA RHEUMATICA ASSOCIATED WITH GIANT CELL ARTERITIS CONFIGURES A SUBTYPE WITH LOWER MORTALITY WITHIN GIANT CELL ARTERITIS
Authors: Carmen de Frutos Fernández, Maria Angeles Martinez Huedo, Irene Monjo, Eugenio de Miguel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Giant cell arteritis (GCA) is the most frequent systemic vasculitis in older than 50 years old, with marked general state involvement or ischemic phenomena that can cause blindness to the patient's death. Its form of presentation is heterogeneous however the therapeutic approach tends to be homogeneous. In recent years, the possible existence of subtypes of the disease has been pointed out and this can have important repercussions in the prognosis and approach of the disease. Two studies have suggested that the coexistence of GCA and Polymyalgia rheumatica (PMR) identifies a subgroup of patients at low risk for developing cranial ischemic symptoms. However, this was refuted by three other studies that did not find that effect. <h3>Objectives</h3> To study if, excluding the articular manifestations, the GCA against the association of PMR with ACG presents a phenotype with clinical differences relevant in clinical practice. <h3>Methods</h3> Retrospective observational study based on data from the Database of Hospital from the Spanish National Health Service with primary or secondary diagnostic of GCA between January 1<sup>st</sup>, 2005 and December 31th, 2015. In this substudy the data demographics and comorbidities and mortality, presenting patients with GCA were collected and compared with patients with GCA and PMR. <h3>Results</h3> The study cohort included 29.576 patients with GCA, of whom 4,189 had PMR as an associated diagnosis. The comorbidities associated with ACG and ACG/PMR and the statistical significance of the differences can be seen in the table. As a relevant fact, a lower risk of mortality was observed in patients presenting GCA along with PMR (OR 0.682 IC95% 0,581-0,801) and a lower frequency of cerebrovascular events and ischemic optic neuropathy. *Statistically significant differences (P &lt; 0.05) DM2: Diabetes mellitus Type 2 <b>PMR</b>: Polymyalgia rheumatica <b>ICC:</b> Congestive heart failure <b>IHM:</b> Ischemic Heart Disease <b>ECV:</b> Cerebrovascular disease <b>ION:</b> ischemic optic neuropathy CCI: Charlson Index of Comorbidities <h3>Conclusion</h3> The patients with GCA with PMR represent a subtype of GCA with lower risk of stroke, ischemic optic neuropathy and mortality than patients with ACG without associated PMR.&nbsp; <h3>Disclosure of Interests:&nbsp;</h3> None declared
A Head-Mounted Camera System Integrates Detailed Behavioral Monitoring with Multichannel Electrophysiology in Freely Moving Mice
Authors: Arne F. Meyer, Jasper Poort, John O’Keefe, Maneesh Sahani, Jennifer F. Linden
Journal: Neuron (2018)

Highlights•Eyes, whiskers, head, and neural activity monitored in freely moving mice•System generates stable video output and leaves mouse behavior largely unchanged•Close link between eye and head movements at both slow and fast timescales•Active head movements in the dark strongly modulate primary visual cortex activitySummaryBreakthroughs in understanding the neural basis of natural behavior require neural recording and intervention to be paired with high-fidelity multimodal behavioral monitoring. An extensive genetic toolkit for neural circuit dissection, and well-developed neural recording technology, make the mouse a powerful model organism for systems neuroscience. However, most methods for high-bandwidth acquisition of behavioral data in mice rely upon fixed-position cameras and other off-animal devices, complicating the monitoring of animals freely engaged in natural behaviors. Here, we report the development of a lightweight head-mounted camera system combined with head-movement sensors to simultaneously monitor eye position, pupil dilation, whisking, and pinna movements along with head motion in unrestrained, freely behaving mice. The power of the combined technology is demonstrated by observations linking eye position to head orientation; whisking to non-tactile stimulation; and, in electrophysiological experiments, visual cortical activity to volitional head movements.
Integration of Visual Information in Auditory Cortex Promotes Auditory Scene Analysis through Multisensory Binding
Authors: Huriye Atilgan, Stephen M. Town, Katherine C. Wood, Gareth P. Jones, Ross K. Maddox, Adrian K.C. Lee, Jennifer K. Bizley
Journal: Neuron (2018)

How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here, we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.
Letter to the editor: Strengthening epidemiological surveillance of Neisseria gonorrhoea – beyond the detection of cases
Authors: Victoria Hernando, Alicia Magistris, Antonio Nicolau, Susana Ramón, Carmen Varela, Marta Ruiz-Algueró, Asunción Diaz
Journal: Eurosurveillance (2019)

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Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies
Authors: Peer Arts, Annet Simons, Mofareh S. AlZahrani, Elanur Yilmaz, Eman AlIdrissi, Koen J. van Aerde, Njood Alenezi, Hamza A. AlGhamdi, Hadeel A. AlJubab, Abdulrahman A. Al-Hussaini, Fahad AlManjomi, Alaa B. Alsaad, Badr Alsaleem, Abdulrahman A. Andijani, Ali Asery, Walid Ballourah, Chantal P. Bleeker-Rovers, Marcel van Deuren, Michiel van der Flier, Erica H. Gerkes, Christian Gilissen, Murad K. Habazi, Jayne Y. Hehir-Kwa, Stefanie S. Henriet, Esther P. Hoppenreijs, Sarah Hortillosa, Chantal H. Kerkhofs, Riikka Keski-Filppula, Stefan H. Lelieveld, Khurram Lone, Marius A. MacKenzie, Arjen R. Mensenkamp, Jukka Moilanen, Marcel Nelen, Jaap ten Oever, Judith Potjewijd, Pieter van Paassen, Janneke H. M. Schuurs-Hoeijmakers, Anna Simon, Tomasz Stokowy, Maartje van de Vorst, Maaike Vreeburg, Anja Wagner, Gijs T. J. van Well, Dimitra Zafeiropoulou, Evelien Zonneveld-Huijssoon, Joris A. Veltman, Wendy A. G. van Zelst-Stams, Eissa A. Faqeih, Frank L. van de Veerdonk, Mihai G. Netea, Alexander Hoischen
Journal: Genome Medicine (2019)

Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test.