tbuckley/cabot-search huggingface dataset:
SAT0498 Abnormal electrocardiographic findings in a scandinavian cohort of patients with idiopathic inflammatory myopathies
Authors: S.S. Korsholm, M. Dastmalchi, A.C. Diederichsen, D.C. Andersson, I.E. Lundberg, N. Witting, M.E. Krogager, T. Friis, S. Jacobsen, J.B. Knudsen, L.P. Diederichsen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Idiopathic inflammatory myopathies (IIMs) are characterised by progressive muscle weakness and muscle fatigue. IIMs frequently appear with other organ involvement, e.g. the heart. Cardiac affection is often subclinical but associated with poor prognosis which makes early detection critical. Presence of autoantibodies is common in IIMs and autoantibodies are important biomarkers to confirm the diagnosis of IIMs. Autoantibodies may even predict organ involvement, e.g. the common myositis specific autoantibody anti-Jo1, which is a marker of lung involvement. So far, an autoantibody predicting cardiac involvement has yet to be identified. <h3>Objectives</h3> The aim of this study was to identify and estimate presence of cardiac involvement detected by electrocardiography (ECG) and to evaluate possible associations between ECG changes and autoantibodies in a Scandinavian cohort of patients with IIMs. <h3>Methods</h3> In a Scandinavian cross-sectional study, 241 patients with polymyositis (PM), dermatomyositis (DM), or inclusion body myositis (IBM) and 48 healthy controls (HCs) were investigated by ECG, basic cardiovascular assessments, and autoantibody profile including myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs). <h3>Results</h3> Compared to HCs, patients with IIMs more frequently had prolongation of QTc (p=0.037) and QRS (p=0.031). All patient groups had significantly longer QTc and QRS duration than HCs. In multivariate regression analysis of patients with IIMs, increased CRP (p=0.006) was associated to increased QTc. Pooled data for patients with IIMs and HCs showed an association between diagnosis of IIM and increased QTc duration (p&lt;0.001). An association between presence of any MAA and QRS duration appeared in patients with IIMs (p=0.019). In pooled data for patients with IIMs and HCs, diagnosis of IIM was associated with QRS duration (p=0.001). <h3>Conclusions</h3> Patients with IIMs, no matter of clinical subgroup, had a higher occurrence of cardiac abnormalities detected by ECG than HCs. Increased CRP and presence of any MAA were associated with increased QTc and QRS duration, respectively. These results support our notion of possible associations between inflammation and autoimmunity and cardiac affection in patients with IIMs. There is now a pressing need to set up a larger prospective study to validate the present findings. <h3>Disclosure of Interest</h3> None declared
Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification
Authors: Xiang-Ping Yao, Xuewen Cheng, Chong Wang, Miao Zhao, Xin-Xin Guo, Hui-Zhen Su, Lu-Lu Lai, Xiao-Huan Zou, Xue-Jiao Chen, Yuying Zhao, En-Lin Dong, Ying-Qian Lu, Shuang Wu, Xiaojuan Li, Gaofeng Fan, Hongjie Yu, Jianfeng Xu, Ning Wang, Zhi-Qi Xiong, Wan-Jin Chen
Journal: Neuron (2018)
Altered immune cell follicular dynamics in HIV infection following influenza vaccination
Authors: Eirini Moysi, Suresh Pallikkuth, Leslie R. De Armas, Louis E. Gonzalez, David Ambrozak, Varghese George, David Huddleston, Rajendra Pahwa, Richard A. Koup, Constantinos Petrovas, Savita Pahwa
Journal: Journal of Clinical Investigation (2018)

HIV infection changes the lymph node (LN) tissue architecture, potentially impairing the immunologic response to antigenic challenge. The tissue-resident immune cell dynamics in virologically suppressed HIV+ patients on combination antiretroviral therapy (cART) are not clear. We obtained LN biopsies before and 10 to 14 days after trivalent seasonal influenza immunization from healthy controls (HCs) and HIV+ volunteers on cART to investigate CD4+ T follicular helper (Tfh) and B cell dynamics by flow cytometry and quantitative imaging analysis. Prior to vaccination, compared with those in HCs, HIV+ LNs exhibited an altered follicular architecture, but harbored higher numbers of Tfh cells and increased IgG+ follicular memory B cells. Moreover, Tfh cell numbers were dependent upon preservation of the follicular dendritic cell (FDC) network and were predictive of the magnitude of the vaccine-induced IgG responses. Interestingly, postvaccination LN samples in HIV+ participants had significantly (P = 0.0179) reduced Tfh cell numbers compared with prevaccination samples, without evidence for peripheral Tfh (pTfh) cell reduction. We conclude that influenza vaccination alters the cellularity of draining LNs of HIV+ persons in conjunction with development of antigen-specific humoral responses. The underlying mechanism of Tfh cell decline warrants further investigation, as it could bear implications for the rational design of HIV vaccines.
Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
Authors: Christina T. Jensen, Josefine Åhsberg, Mikael N.E. Sommarin, Tobias Strid, Rajesh Somasundaram, Kazuki Okuyama, Jonas Ungerbäck, Jussi Kupari, Matti S. Airaksinen, Stefan Lang, David Bryder, Shamit Soneji, Göran Karlsson, Mikael Sigvardsson
Journal: The Journal of Experimental Medicine (2018)

To understand the developmental trajectories in early lymphocyte differentiation, we identified differentially expressed surface markers on lineage-negative lymphoid progenitors (LPs). Single-cell polymerase chain reaction experiments allowed us to link surface marker expression to that of lineage-associated transcription factors (TFs) and identify GFRA2 and BST1 as markers of early B cells. Functional analyses in vitro and in vivo as well as single-cell gene expression analyses supported that surface expression of these proteins defined distinct subpopulations that include cells from both the classical common LPs (CLPs) and Fraction A compartments. The formation of the GFRA2-expressing stages of development depended on the TF EBF1, critical both for the activation of stage-specific target genes and modulation of the epigenetic landscape. Our data show that consecutive expression of Ly6D, GFRA2, and BST1 defines a developmental trajectory linking the CLP to the CD19+ progenitor compartment.
FRI0365 Factors associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus
Authors: I.-W. Baek, K.-J. Kim, Y.-J. Park, W.-U. Kim, C.-S. Cho
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Myocardial damage is common and often silent in patients with systemic lupus erythematosus (SLE). In this study, we investigated the clinical parameters associated with left ventricular diastolic dysfunction in SLE patients using algorithms of 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) recommendations. <h3>Methods</h3> Sixty consecutive SLE patients and 38 controls matched for age and sex who were free of clinical cardiovascular disease were enrolled. Left ventricular diastolic dysfunction was assessed by echocardiography using 2016 ASE/EACVI guidelines. The demographic, clinical and laboratory data were obtained from medical records. <h3>Results</h3> Diastolic dysfunction was more common in SLE patients compared with controls (38.3% versus 13.2%, p=0.011), while LV ejection fraction was not different between groups. When patients were divided into 2 groups according to the presence of diastolic dysfunction, patients with diastolic dysfunction had higher prevalence of hypertension (p&lt;0.001), dyslipidemia (p=0.031) and chronic kidney disease (p=0.045), but there was no difference between groups with regard to other organ involvement or autoantibody profile. Importantly, patients with diastolic dysfunction showed significantly higher SLICC/ACR damage index (p=0.001) and C-reactive protein levels (p=0.005). In multivariate regression analysis, hypertension (OR=16.6. 95% CI=3.466–79.479, p&lt;0.001), higher SLICC/ACR damage index (OR=1.68, 95% CI=1.039–2.720, p=0.034), and CRP level (OR=1.12, 95% CI=1.004–1.254, p=0.042) was independently associated with diastolic dysfunction in SLE patients <h3>Conclusions</h3> Diastolic dysfunction is more common in SLE patients, and overall inflammatory burden reflected by SLICC/ACR damage index as well as conventional cardiovascular risk factors are associated with development of diastolic dysfunction in SLE patients. <h3>Disclosure of Interest</h3> None declared
THU0665 Pharmacovigilance surveillance of autoimmune diseases induced by biological agents: a review of 16123 cases (AEBIOGEAS-SEMI REGISTRY)
Authors: M. Ramos-Casals, S. Retamozo, A. Flores-Chavez, B. Kostov, A. Sisó-Almirall, M. Pérez-de-Lis, R. Pérez-Alvarez, P. Brito-Zerón
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> The increasing use of biological agents has been linked with the paradoxical development of autoimmune processes. The scenario has dramatically change in recent years due to the increased number of biologics used in daily practice and the emerging use of biologics in patients with solid cancers. <h3>Methods</h3> In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use and safety of biological agents in adult patients. The aeBIOGEAS Registry (autoimmune events) was designed to collect data on autoimmune diseases secondary to the use of biologic agents, with the aim of formulating a standardised, consensual protocol for these patients, through a systematic and yearly MEDLINE search. We present the updated results of the aeBIOGEAS Registry (cases collected until Dec 31, 2017). <h3>Results</h3> The aeBIOGEAS Registry currently includes 16 123 cases of more than 50 different systemic and organ-specific triggered autoimmune diseases related to the administration of 46 different biological molecules in patients with inflammatory diseases (9907 cases, overwhelmingly rheumatic diseases in 8639) and cancer (6216 cases, overwhelmingly solid neoplasia in 5955). The main biological agents identified consisted of anti-TNF agents in 9514 cases (mainly adalimumab in 4147, infliximab in 3028 and etanercept in 1648), checkpoint inhibitors in 5264 (overwhelmingly the CTL4 inhibitor ipilimumab in 4980 cases), thyrosine kinase inhibitors in 952 (mainly imatinib in 377 cases) and B-cell targeted therapies in 298 cases. Organ-specific classification of triggered autoimmune diseases included cutaneous (n=7140), digestive (n=2323), endocrine (n=1701), pulmonary (n=1683), systemic/rheumatic (n=1230), neurological (n=1172), ocular (n=349), cardiac (n=322), haematological (n=106) and renal (n=96) diseases. The most frequently reported induced individual autoimmune diseases were psoriasis (n=6401), enterocolitis (n=1947), interstitial lung diseases (n=1680), thyroiditis (n=1076), hypophysitis (n=492), demyelinating CNS diseases (n=452), peripheral neuropathies (n=431), lupus (n=371), vasculitis (n=339), uveitis (n=298), vitiligo (n=256) and sarcoidosis (n=185). <h3>Conclusions</h3> The number and diversity of induced autoimmune disorders is increasing exponentially in parallel with the increased use of biological therapies in neoplasic diseases, which are currently representing 40% of reported cases. Management of these biologic-induced autoimmune diseases will be an increasing multidisciplinary clinical challenge in the daily practice in the next years. <h3>Disclosure of Interest</h3> None declared
Review: In major depressive disorder, antidepressant drugs improve short-term response compared with placebo
Authors: Brian Budenholzer
Journal: Annals of Internal Medicine (2018)

Source Citation Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018. [Epub ahead of print]. 29477251
RNAi-Based GluN3A Silencing Prevents and Reverses Disease Phenotypes Induced by Mutant huntingtin
Authors: Sonia Marco, Alvaro Murillo, Isabel Pérez-Otaño
Journal: Molecular Therapy (2018)

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. HD symptoms include severe motor, cognitive, and psychiatric impairments that result from dysfunction and later degeneration of medium-sized spiny neurons (MSNs) in the striatum. A key early pathogenic mechanism is dysregulated synaptic transmission due to enhanced surface expression of juvenile NMDA-type glutamate receptors containing GluN3A subunits, which trigger the aberrant pruning of synapses formed by cortical afferents onto MSNs. Here, we tested the therapeutic potential of silencing GluN3A expression in YAC128 mice, a well-established HD model. Recombinant adeno-associated viruses encoding a short-hairpin RNA against GluN3A (rAAV-shGluN3A) were generated, and the ability of different serotypes to transduce MSNs was compared. A single injection of rAAV9-shGluN3A into the striatum of 1-month-old mice drove potent (>90%) and long-lasting reductions of GluN3A expression in MSNs, prevented dendritic spine loss and improved motor performance in YAC128 mice. Later delivery, when spine pathology is already apparent, was also effective. Our data provide proof-of-concept for GluN3A silencing as a beneficial strategy to prevent or reverse corticostriatal disconnectivity and motor impairment in HD and support the use of RNAi-based or small-molecule approaches for harnessing this therapeutic potential.
How to build a lung: latest advances and emerging themes in lung bioengineering
Authors: Martina M. De Santis, Deniz A. Bölükbas, Sandra Lindstedt, Darcy E. Wagner
Journal: European Respiratory Journal (2018)

Chronic respiratory diseases remain a major cause of morbidity and mortality worldwide. The only option at end-stage disease is lung transplantation, but there are not enough donor lungs to meet clinical demand. Alternative options to increase tissue availability for lung transplantation are urgently required to close the gap on this unmet clinical need. A growing number of tissue engineering approaches are exploring the potential to generate lung tissue ex vivo for transplantation. Both biologically derived and manufactured scaffolds seeded with cells and grown ex vivo have been explored in pre-clinical studies, with the eventual goal of generating functional pulmonary tissue for transplantation. Recently, there have been significant efforts to scale-up cell culture methods to generate adequate cell numbers for human-scale bioengineering approaches. Concomitantly, there have been exciting efforts in designing bioreactors that allow for appropriate cell seeding and development of functional lung tissue over time. This review aims to present the current state-of-the-art progress for each of these areas and to discuss promising new ideas within the field of lung bioengineering.
Impact of Cardioprotective Therapies on the Edema-Based Area at Risk by CMR in Reperfused STEMI
Authors: Heerajnarain Bulluck, Mervyn H.H. Chan, Valeria Paradies, Jennifer A. Bryant, Sauri Hernández-Reséndiz, Hector A. Cabrera-Fuentes, Timothy J. Watson, Mark Y. Chan, Jack W. Tan, Derek J. Hausenloy
Journal: Journal of the American College of Cardiology (2018)
A multi-organ loss of tissue phenotype in COPD: involvement of the functional muscle–bone unit
Authors: Toshihiro Sugiyama
Journal: European Respiratory Journal (2018)

In the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) chronic obstructive pulmonary disease (COPD) cohort including 1817 men and women aged 40–75 years with full computed tomography (CT) data, Celli et al. [1] showed that emphysema progression was associated with loss of extrapulmonary tissues such as skeletal muscle and bone. I agree with the authors that identification of the patients they proposed to name a multi-organ loss of tissue (MOLT) COPD phenotype is important because of worse clinical outcomes [1] and would also like to point out that physical activity plays a significant role in the association. Physical activity would be significantly involved in the multi-organ loss of tissue phenotype in COPD <http://ow.ly/ez2t30jLY4E>
Abstract 16614: Outcomes Among Nonagenarians Presenting With Acute Coronary Syndrome Undergoing Coronary Angiography: a National Veterans Administration Database Study
Authors: Abhishek C Sawant, Vasvi Singh, Meg E Plomondon, Thomas Maddox, Kevin P Josey, Ali Sheikh, Zaid Said, Bharath Rajagopalan, Matthew McIntosh, Sebastian Wilk, John Corbelli
Journal: Circulation (2016)

Background: Patients often present with acute coronary syndrome (ACS) during their 8th and 9th decades of life. This subpopulation is often underrepresented in clinical trials, receives suboptimal ...
Abstract 18165: Fluoroscopic-Free Ablation with 3D Imaging: Immediate Procedural Success and Complications
Authors: Ryan T Kipp, James A Oujiri, Jason Boynton, Nicholas Von Bergen, Lee Eckhardt
Journal: Circulation (2014)

Introduction: Ablation is a curative procedure for many supra-ventricular tachycardia’s. Classically, fluoroscopic imaging has been used to guide catheter placement and ablation. Prolonged radiation exposure from complicated or repeat ablation may increase the lifetime risk of cancer through stochastic effects, particularly in young patients and healthcare providers. In addition, protective lead aprons and vests required for healthcare providers and can result in physical injury from extended, repeated use. Use of 3D electro-anatomical navigation systems has significantly reduced the amount of fluoroscopy used for ablation. We extended this further by using of 3D navigation systems in a complete fluoro-free (FF) ablation. Here, we report safety and efficacy of this technique in a large patient cohort. Methods: From February, 2010 - March, 2013 all ablations performed FF at a single academic medical center were enrolled in an ablation registry. Patient and procedural characteristics for each ablation were collected. We report the ablation characteristics, acute procedural success, and complication rate associated with FF ablation. Results: During the study period, 102 consecutive ablations by two operators were performed with the intention of FF. 14 of 102 cases required fluoro guidance at the discretion of the operator (13.7% cross-over). The average patient age was 22.1 years, 49% were male. The 2 most common diagnoses for FF ablation were AVNRT (58.4%) and AVRT (24.8%). Of the 88 FF cases, the acute procedural success rate was 97%. 77.9% were performed with cryoablation. 4.6% of FF cases suffered minor complications including: 2 with transient heart block, 1 groin hematoma managed conservatively, and 1 transient prolongation of the AH interval. There were no cases of permanent heart block. There were no significant complications in the FF group. Conclusions: Ablation of supra-ventricular tacharrhythmias without use of fluoroscopy has a high acute procedural success rate with low incidence of procedural complication. Use of this technique completely relieves the patient and healthcare of radiation exposure, eliminating radiation stochastic effects and obviating the need for protective shielding.
AB0501 Adverse events with treatment regimens of rheumatoid arthritis (RA) reported by patients applying smart system of disease management (SSDM) mobiles tools: a cohort study of ra patients in china
Authors: Y. Wang, J. Yang, H. Wei, C. Li, R. Mu, B. Wu, H. Wang, Y. Wang, X. Wang, H. Guo, J. Xue, J. Ru, X. Xin, F. Zhang, L. Kang, H. Liu, J. YuHua, Y. Liu, F. Xiao, J. Huang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hepatic, hematologic and other adverse events (AE) during treatment in RA patients are unavoidable. And monitoring AE in long-term treatment is quite necessary as a part of chronic disease management. SSDM is a smart mobile tool to help patients upload their therapeutic regimens, lab test records and report AEs. Our previous study showed that patients in China can master the application of SSDM after training. <h3>Objectives</h3> To determine and compare the incidence of adverse events during treatment of RA with different therapeutic regimens, focusing on mono and combination therapy. <h3>Methods</h3> The SSDM includes interfaces of both physicians' and patients' application. Patients were educated to enter the data of lab test records and treatment regiments once a month, all data can be synchronised automatically to the authorised physicians' mobile tool, which formed a large patient reported database. The rheumatologists can also adjust treatment regiments base on patients' profile. <h3>Results</h3> From Aug 2014 to Jan 2018, a total of 7048 RA patients from 480 centres in China were entered in the cohort study. These patients contributed more than 12 600 patient-years (PY) of total followup. The mean age was 48.98±16.08 (18 to 99) years and the median disease duration was 23.27 months. The treatment regimens include mono or combination of leflunomide(LEF), MTX, hydroxycholoqine (HCQ), sulfasalazine(SSZ), glucocorticoid(GC), biologic DMARD, Tripterygium wilfordii, meloxicam, celecoxib, iguratimod, etc. In this database the five most common treatment regimens is LEF monotherapy (3801 PY), MTX monotherapy (1321 PY), LEF +MTX (1086 PY), HCQ monotherapy (715 PY), LEF +HCQ (576 PY). The incidence rate of hepatic events was lower for LEF monotherapy (35 events/1000 PY) than MTX (52 events/1000 PY) and LEF +MTX combination therapy (115 events/1000 PY) (p&lt;0.01). The incidence rate of leukopenia was lower for LEF monotherapy (42 events/1000 PY) and MTX monotherapy (39 events/1000 PY) than LEF +MTX combination therapy (84 events/1000 PY) (p&lt;0.01). <h3>Conclusions</h3> The findings show that mono or combination of csDMARDs are the most commonly used drugs in Chinese RA patients. And AEs may be well described in this patient report database because of the large sample sizes and empowering patient themselves. RA patients can get better safety in the long-term treatment via SSDM. <h3>Disclosure of Interest</h3> None declared