tbuckley/cabot-search huggingface dataset:
Abstract 13074: Convergent Ablation for Long-Standing Persistent Atrial Fibrillation: Single Center Experience From a Large Regional Medical Center
Authors: Bryan Piedad, Theresa Luu, Jacob Blatt, Michael Riley, Cesar Egoavil, John Dercola, Karen Martinelli, Narendra Kanuru
Journal: Circulation (2015)

Introduction: The treatment of long-standing, persistent AF is challenging. Conventional transvenous radiofrequency (RF) ablation strategies have provided only modest success, often requiring multiple procedures to maintain normal sinus rhythm. The convergent ablation procedure is a hybrid approach, involving a minimally invasive epicardial ablation combined with a traditional transvenous endocardial ablation. This comprehensive approach may offer a more effective treatment for long-standing persistent AF. Methods: From 12/2013 through 05/2015, we performed 50 convergent ablations (40 male; 10 female) for symptomatic, long-standing persistent AF. Mean age was 64.1±9.2 years with a mean CHADS-VASC score of 2.5±1.5. Mean LA volume was 161.5±44.5 cc. Mean weight was 103.3 kg ± 23.1 kg, and mean LVEF was 51.7%±21.7%. All patients had failed at least one anti-arrhythmic medication. Epicardial ablation was performed via a sub-xyphoid, endoscopic approach followed by transvenous endocardial ablation (32 RF and 18 cryoablation). Transvenous cavo-tricuspid isthmus (CTI) ablation was performed in all patients using RF energy. Results: Mean procedural time was 2.4±0.6 hours (epicardial) and 2.9±0.75 hours (endocardial). Acute procedural success was 100%, defined as complete pulmonary vein isolation, comprehensive ablation of the posterior LA, and CTI block. Mean hospital stay was 3.4±1.7 days. At mean follow-up of 206±150 days, 47 remain in NSR (94%). Of those patients who underwent transvenous radiofrequency (RF) ablation, 29 of 32 were in sinus rhythm (91%), while 18 of 18 of those who underwent cryo-ablation were in sinus rhythm (100%). At last follow-up, anti-arrhythmic therapy was discontinued in 22 patients (44%). Major complications occurred in 2 patients (4%): rectus hematoma and pericardial tamponade. Conclusions: Convergent ablation is an effective treatment for long-standing persistent AF, demonstrating high success rates with low complication rates. Longer follow-up and prospective, randomized trials are needed.
AB0727 Increased Rates of Hypertension in Patients with Psoriatic Arthritis Compared To Psoriasis Alone: Results from The UK Biobank: Table 1.
Authors: E. Bellou, S.M.M. Verstappen, M. Cook, J.C. Sergeant, R.B. Warren, A. Barton, J. Bowes
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with the presence of psoriasis. Lifestyle factors such as body mass index (BMI), smoking and alcohol consumption have been reported to contribute to the risk of both diseases. These risk factors also contribute to cardiovascular disease (CVD) which is a major cause of morbidity and mortality in patients with psoriasis and PsA. <h3>Objectives</h3> To compare lifestyle factors between individuals with PsA, psoriasis and a control group and to assess the association between these inflammatory diseases and CVD outcomes utilising the UK Biobank resource. <h3>Methods</h3> UK Biobank recruited 502,664 people aged 40–70 years in the UK between 2006 and 2010. Data on lifestyle, sociodemographics, health and medical history were collected at the assessment visit by questionnaire and interview by research nurse. Participants were asked if they have ever been diagnosed by a physician with a disease. Lifestyle factors including alcohol (current or past drinker) and smoking status (ever or never) were recorded and height and weight measured to calculate BMI. In this cross-sectional study, the frequency of these factors was compared between PsA, psoriasis and healthy controls using logistic or linear regression analyses depending on the outcome, adjusting for age and gender. Comparison between disease groups was performed by linear combinations of coefficients post estimation. Three CVD outcomes: heart attack, angina and hypertension, were tested for association with disease group using logistic regression including BMI, smoking, alcohol, age and sex as covariates. Odds ratios (OR) and β coefficients are reported with 95% confidence intervals (CI). <h3>Results</h3> 862 people with PsA, 4,761 with psoriasis and 465,371 control participants were included in the study (Table). Compared to the control group; both the PsA and psoriasis groups had higher BMI (β 1.43 (95% CI 1.11:1.75) and 0.72 (0.58:0.85) respectively), the psoriasis group smoked more (OR 1.63 (1.54:1.72)) and patients with PsA were less likely to be current drinkers (OR 0.68 (0.55:0.85)). Compared to patients with psoriasis, patients with PsA had higher BMI (β 0.69 (0.32:1.06)) and were less likely to be ever smokers and current drinkers (OR 0.70 (0.61:0.81) and 0.65 (0.51:0.83), respectively). Finally, hypertension was more prevalent in PsA compared to the control and psoriasis cohorts (OR 1.71 (1.48:1.97) and 1.55 (1.33:1.82), respectively). <h3>Conclusions</h3> Using a large population based cohort we show that self-reported CVD outcomes, in particular hypertension, are significantly higher in PsA compared to psoriasis independently of known CVD risk factors. The results contribute to our understanding of the lower quality of life reported by patients with PsA. <h3>Disclosure of Interest</h3> None declared
SAT0123 Radiographic Severity of Rheumatoid Arthritis in Latin American Patients: Results from The Gladar Cohort
Authors: L. Massardo, F. Schweitzer, C. Pineda, B. Pons-Estel, M. Cardiel, E. Soriano, C. Galarza, R. Levy, M. Sacnum, C. Caballero-Uribe, W. Bianchi, H. Gonzalez, R. Montufar, R. Pinto, L. Ramirez, C. Zerbini, I. Laurindo, I. Barra
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> More radiographic damage occurs within the first year of rheumatoid arthritis (RA). Erosions occurring preferentially in feet and joint space narrowing (JSN) in wrists have been described in early RA. Little is known of radiographic progression in Latin American patients with early RA. <h3>Objectives</h3> To describe radiographic changes in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline, a multicenter observational study. <h3>Methods</h3> Patients were enrolled in GLADAR (<i>Grupo Latino Americano de estudio De Artritis Reumatoide)</i>, the largest longitudinal cohort of early RA (&lt;1 year from onset) in LA, from 2004/2005–2008. Demographic and clinical data were obtained and sets of hand/wrist and foot radiographs were scored using the modified Sharp/ Van der Heijde scoring system. <h3>Results</h3> A total of 507 patients with radiographic readings were evaluated. The mean radiographic score was 23.37 at baseline visit; 56.2% had erosions and 97.8% joint space narrowing (JSN). Among patients with JSN, the mean score was 20.97. JSN occurred in hands/wrists (97%) and feet (72%), while erosions were observed in hands/wrists (42.8%) and feet (28.8%). X-rays of 253 patients were assessed after at one-year of follow-up; of 132 without erosions, 14.4% developed erosions; and 100% JSN. No significant differences were observed among patients who progressed according to socio-demographic features, use of DMARDS, use of prednisone and rheumatoid factor positivity. <h3>Conclusions</h3> This is the largest radiographic study of Latin American RA patients. Damage occurs early in the disease. Surprisingly, JSN is the most common radiographic change and occurs more often in hands/wrist. Further studies are needed to understand the meaning of the greater breakdown in cartilage compared to erosions in this population. <h3>References</h3> Loreto Massardo, Bernardo A. Pons-Estel, Daniel Wojdyla, Mario H. Cardiel, C. Pineda, E. R. Soriano et al; GLADAR. Early Rheumatoid Arthritis in Latin America: Low Socioeconomic Status Related to High Disease Activity at Baseline. Arthritis Care &amp; Research Vol. 64, No. 8, August 2012, pp 1135–1143 Cardiel M.H., Pons-Estel B.A., Wojdyla D., Saurit V., Marcos JC., Pinto MR., Cordeiro de Azevedo A.B., da Silveira I.G., Radominski S.C., Ximenes A.C., Massardo L., Ballesteros F., Rojas-Villarraga A., Oñate R.V., Hernandez M.P., Esquivel-Valerio J.A., García-De La Torre I., Khoury V.J., Millán A., Soriano E.R.; GLADAR. Treatment of early rheumatoid arthritis in a multinational inception cohort of Latin American patients: the GLADAR experience. J Clin Rheumatol. 2012 Oct;18(7):327–35. <h3>Disclosure of Interest</h3> None declared
Patient Derived Xenotransplantation Model of Atypical Chronic Myeloid Leukemia (aCML)
Authors: Arnold Kloos, Felicitas Thol, Sabrina Klesse, Alessandro Liebich, Arne Trummer, Renate Schottmann, Rubén Trespando Jiménez, Gudrun Göhring, Brigitte Schlegelberger, Arnold Ganser, Michael Heuser
Journal: Blood (2015)
A novel glucagon‐like peptide 1/glucagon receptor dual agonist improves steatohepatitis and liver regeneration in mice
Authors: M. Pilar Valdecantos, Virginia Pardo, Laura Ruiz, Luis Castro‐Sánchez, Borja Lanzón, Elisa Fernández‐Millán, Carmelo García‐Monzón, Ana I. Arroba, Águeda González‐Rodríguez, Fernando Escrivá, Carmen Álvarez, Francisco J. Rupérez, Coral Barbas, Anish Konkar, Jacqui Naylor, David Hornigold, Ana Dos Santos, Maria Bednarek, Joseph Grimsby, Cristina M. Rondinone, Ángela M. Valverde
Journal: Hepatology (2016)

Because nonalcoholic steatohepatitis (NASH) is associated with impaired liver regeneration, we investigated the effects of G49, a dual glucagon‐like peptide‐1/glucagon receptor agonist, on NASH and hepatic regeneration. C57Bl/6 mice fed chow or a methionine and choline–deficient (MCD) diet for 1 week were divided into 4 groups: control (chow diet), MCD diet, chow diet plus G49, and M+G49 (MCD diet plus G49). Mice fed a high‐fat diet (HFD) for 10 weeks were divided into groups: HFD and H+G49 (HFD plus G49). Following 2 (MCD groups) or 3 (HFD groups) weeks of treatment with G49, partial hepatectomy (PH) was performed, and all mice were maintained on the same treatment schedule for 2 additional weeks. Analysis of liver function, hepatic regeneration, and comprehensive genomic and metabolic profiling were conducted. NASH was ameliorated in the M+G49 group, manifested by reduced inflammation, steatosis, oxidative stress, and apoptosis and increased mitochondrial biogenesis. G49 treatment was also associated with replenishment of intrahepatic glucose due to enhanced gluconeogenesis and reduced glucose use through the pentose phosphate cycle and oxidative metabolism. Following PH, G49 treatment increased survival, restored the cytokine‐mediated priming phase, and enhanced the proliferative capacity and hepatic regeneration ratio in mice on the MCD diet. NASH markers remained decreased in M+G49 mice after PH, and glucose use was shifted to the pentose phosphate cycle and oxidative metabolism. G49 administered immediately after PH was also effective at alleviating the pathological changes induced by the MCD diet. Benefits in terms of liver regeneration were also found in mice fed HFD and treated with G49. Conclusion : Dual‐acting glucagon‐like peptide‐1/glucagon receptor agonists such as G49 represent a novel therapeutic approach for patients with NASH and particularly those requiring PH. (H epatology 2017;65:950‐968).
Outcomes In Patients with Multiple Myeloma Following Autologous Stem Cell Transplantation Using Intravenous Busulfan and Melphalan: A Matched Comparison to a Double Autologous Transplant Strategy
Authors: Margarita Blanes, Javier De La Rubia, Juan-Jose Lahuerta, José David Gonzalez, Paz Ribas, Carlos Solano, Miguel Angel Sanz
Journal: Blood (2010)
Standards of Medical Care in Diabetes—2012
Journal: Diabetes Care (2011)

Table 3dCategories of increased risk for diabetes (prediabetes)* FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG) OR 2-h plasma glucose in the 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT) OR A1C 5.7-6.4% *For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher ends of the range.care.diabetesjournals.org
Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction
Authors: Li Zhang, Zhenxing Sun, Pingping Ren, Manjie You, Jing Zhang, Lingyun Fang, Jing Wang, Yihan Chen, Fei Yan, Hairong Zheng, Mingxing Xie
Journal: Theranostics (2016)

Hypoxia-inducible factor 1α (HIF-1α) plays a critical protective role in ischemic heart disease. Under normoxic conditions, HIF-1α was degraded by oxygen-dependent prolyl hydroxylase-2 (PHD2). Gene therapy has become a promising strategy to inhibit the degradation of HIF-1α and to improve cardiac function after ischemic injury. However, conventional gene delivery systems are difficult to achieve a targeted and localized gene delivery into the ischemic myocardia. Here, we report the localized myocardial delivery of shRNA against PHD2 through ultrasound-targeted microbubble destruction (UTMD) for protection the heart from acute myocardial infarction. In this study, a novel cationic microbubble was fabricated by using of the thin-film hydration and sonication method. The resulting microbubbles had a 28.2 ± 2.21 mV surface zeta potential and could greatly improve DNA binding performance, achieving 17.81 ± 1.46 μg of DNA loading capacity per 5 × 108 microbubbles. Combined with these cationic microbubbles, UTMD-mediated gene delivery was evaluated and the gene transfection efficiency was optimized in the H9C2 cardiac cells. Knockdown of PHD2 gene was successfully realized by UTMD-mediated shPHD2 transfection, resulting in HIF-1α-dependent protective effects on H9C2 cells through increasing the expression of HIF-1α, VEGF and bFGF. We further employed UTMD-mediated shPHD2 transfection into the localized ischemic myocardia in a rat ischemia model, demonstrating significantly reduced infarct size and greatly improved the heart function. The silencing of PHD2 and the up-regulation of its downstream genes in the treated myocardia were confirmed. Histological analysis further revealed numbers of HIF-1α- and VEGF-, and CD31-positive cells/mm2 in the shPHD2-treated group were significantly greater than those in the sham or control vector groups (P < 0.05). In conclusion, our study provides a promising strategy to realize ultrasound-mediated localized myocardial shRNA delivery to protect the heart from acute myocardial infarction via cationic microbubbles.
PWE-023 Vitamin D Enhances The Ability of Anti-TNF Therapy to Suppress Dendritic Cell Activity in Crohn’s Disease
Authors: PA Hendy, D Reddi, D Barnardo, L Durant, A Noble, P Bhat, N English, SC Knight, AL Hart
Journal: Gut (2016)

<h3>Introduction</h3> Dendritic cells (DC) can determine whether the mucosal immune system mounts an inflammatory or regulatory response to antigen and may contribute to the pathogenesis of Crohn’s disease. Vitamin D down-regulates DC inflammatory responses and could prove beneficial as a treatment adjunct in Crohn’s. This study assessed the effect of high dose parenteral vitamin D treatment on circulating DC phenotype and function in patients with active luminal Crohn’s receiving anti-TNFα therapy. <h3>Methods</h3> Peripheral blood mononuclear cells were isolated from 13 patients with active luminal Crohn’s and suboptimal vitamin D levels prior to and 6 weeks after starting anti-TNFα (infliximab) therapy. Patients with low vitamin D (&lt;50nmol/L) were also given a single high dose of parenteral vitamin D (300,000 international units 1,25(OH)<sub>2</sub> vitamin D3). Flow cytometry was used to identify total DC, (HLA-DR<sup>+</sup> cells negative for markers of other cell lineages (CD3, CD14, CD16, CD19 &amp; CD34)). DC were further subtyped as myeloid (mDC, CD11c<sup>+</sup>CD123<sup>−</sup>). Expression of phenotypic markers (including maturation and homing markers and pattern recognition receptors) and on-going DC cytokine production during 4 hours’ culture were assessed. <h3>Results</h3> Production of TNFα by myeloid DC was significantly reduced (p = 0.016 Fig C) in those patients who received vitamin D alongside anti-TNFα therapy; without vitamin D treatment, TNFα production by myeloid DC did not decrease significantly after anti-TNFα therapy (p = 0.96 Fig B). There was a significant negative correlation between change in vitamin D level and change in TNFα production by myeloid DC (p = 0.025, correlation coefficient =0.68 Fig D). An increase of serum 25(OH)vitamin D greater than 20 nmol/m was associated with a decrease in myeloid DC TNFα production. Anti-TNFα therapy alone induced a significant upregulation of the skin homing marker cutaneous lymphocyte antigen (CLA) on myeloid DC (p = 0.0055), an effect which was not seen in patients receiving adjunctive vitamin D. <h3>Conclusion</h3> High doses of parenteral vitamin D in patients with Crohn’s promotes anti-TNFα down-regulation of circulating myeloid DC production of TNFα which may influence the subsequent interaction of DC and T cells. TNFα promotes a TH-1/ TH-17 response characteristic of Crohn’s inflammation; thus the ability of vitamin D to further block TNFα production may promote a more regulatory T cell response and improve outcomes when used as an adjunct to anti-TNFα therapy. The down-regulation of skin homing marker CLA by vitamin D may be clinically useful in those patients suffering cutaneous sequelae of anti-TNFα therapy. <h3>Disclosure of Interest</h3> None Declared
RNAi-Based Functional Genomics Screening of the Human Kinome Identifies Major Growth Regulating Kinases in Acute Myeloid Leukemia Cells
Authors: Raoul Tibes, Ashish Choudhary, Amanda Henrichs, Sadia Guled, Irma Monzon, Lourdes Peralta, Jeff Kiefer, David Azorsa
Journal: Blood (2008)
IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer
Authors: Lei Wang, Andrea K. Miyahira, Diana L. Simons, Xuyang Lu, Andrew Y. Chang, Carrie Wang, Maria A. Suni, Vernon C. Maino, Frederick M. Dirbas, John Yim, James Waisman, Peter P. Lee
Journal: Cancer Research (2016)

Abstract IL6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties, which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL6 on cancer cells. How IL6 modulates the host immune response in cancer patients is unclear. Here, we show the IL6 signaling response in peripheral blood T cells is impaired in breast cancer patients and is associated with blunted Th17 differentiation. The mechanism identified involved downregulation of gp130 and IL6Rα in breast cancer patients and was independent of plasma IL6 levels. Importantly, defective IL6 signaling in peripheral blood T cells at diagnosis correlated with worse relapse-free survival. These results indicate that intact IL6 signaling in T cells is important for controlling cancer progression. Furthermore, they highlight a potential for IL6 signaling response in peripheral blood T cells at diagnosis as a predictive biomarker for clinical outcome of breast cancer patients. Cancer Res; 77(5); 1119–26. ©2016 AACR.
SP0144 Ultrasound of The Nail; Why Use It in Rheumatology?
Authors: I. Janta
Journal: Annals of the Rheumatic Diseases (2016)

Nail psoriasis represents an important feature of psoriasis and psoriatic arthritis patients. In psoriasis patients, nail involvement represents a risk factor for psoriatic arthritis. Moreover, nail psoriasis was associated with distal interphalangeal joint arthritis. It is also one of the CASPAR classification criteria for psoriatic arthritis. The complex anatomy of the nail, including the enthesis complex, makes the clinical assessment difficult, as well as the accurate description of the pathology for each structure. Studies have shown a link between nail, extensor tendon enthesis and DIP joints involvement in psoriatic and psoriatic arthritis patients. Ultrasound of the nail includes the evaluation of nail plate, nail bed, and extensor tendon enthesis. Ultrasound of the normal nail plate shows a trilaminar structure: two hyperechoic lines, the ventral and dorsal, separated by a hypoechoic line. The nail bed appears like a hypoechoic band, between the ventral plate and the bone. Some Doppler signals may be seen in the normal nail bed. In early nail involvement, irregularities and loss of sharpness of the dorsal plate can be seen. As the disease progresses, loss of sharpness of ventral plate and loss of trilaminar structure can be seen. In the nail bed involvement, the distance between the ventral plate and the bone can be increased. Also, an increase of Doppler signal has been reported. Compared to rheumatoid arthritis patients, different patterns of both nail plate and nail bed involvement have been seen in psoriatic arthritis patients. <h3>Disclosure of Interest</h3> None declared
AB0202 Hands Magnetic Resonance Imaging (MRI) in Patients with Seronegative Arthritis
Authors: I. Nayshtetik, L. Khimion, O. Piura, O.B. Yaschenko, Y. Kovalenko
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> It is proved that early treatment can modify the further course of rheumatoid arthritis (RA), so early diagnosis is very important for better results of treatment. at present the most sensitive method for the detection of significant changes in the joints in the early stages of RA is magnetic resonance imaging (MRI). <h3>Objectives</h3> We have used this method to detect early RA in patients with seronegative (anticitrullinated peptide antibody (ACPA)/RF –negative) arthritis.<sup>2</sup> <h3>Methods</h3> 52 ACPA/RF-negative patients aged between 18 to 65 years with undifferentiated arthritis lasted for no more than 6 months and no clinical signs of hands and wrists joints involvement underwent MRI of hands and wrists; level of CRP and ESR was determined as well. Synovitis and bone marrow oedema (BME) were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging scoring system. <h3>Results</h3> In 22 of 52 patients (42.31%) MRI had detected significant signs of inflammation and BME in small hands joint and/or wrists which was used to establish diagnosis of early RA. The hither synovitis scores were correlated with CRP levels (P=0.007) and ESR (P=0.022). <h3>Conclusions</h3> MRI signs of synovitis in the small joints of the hands and wrists are observed in a significant amount of patients (42.31%) with seronegative arthritis without clinical signs of hands joints or wrists involvement, which can be used for early RA detection in patients without enough RA diagnostic criteria.<sup>1</sup> <h3>References</h3> Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569–81. Scott DL, Pugner K, Kaarela K, Doyle DV, Woolf A, Holmes J, et al. The links between joint damage and disability in rheumatoid arthritis. Rheumatology (Oxford)2000;39:122–32. <h3>Disclosure of Interest</h3> None declared
IMPS-04TUNING SENSITIVITY OF CHIMERIC ANTIGEN RECEPTOR TO EGFR DENSITY LIMITS RECOGNITION OF NORMAL TISSUE WHILE MAINTAINING POTENT ANTI-TUMOR ACTIVITY
Authors: Hillary Caruso, Lenka Hurton, Amer Najjar, David Rushworth, Sonny Ang, Simon Olivares, Tiejuan Mi, Kirsten Switzer, Harjeet Singh, Helen Huls, Dean Lee, Richard Champlin, Amy Heimberger, Laurence Cooper
Journal: Neuro-Oncology (2015)