tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of ATA129, Partially Matched Allogeneic Third-Party Epstein-Barr Virus-Targeted Cytotoxic T Lymphocytes in a Multicenter Study for Post-Transplant Lymphoproliferative Disorder
Authors: Susan Prockop, Ai Li, Robert A Baiocchi, Nancy Bunin, Kris Michael Mahadeo, Eneida R. Nemecek, Sarah Nikiforow, Ran Reshef, Donald Edward Tsai, Willis H. Navarro, Richard J. O'Reilly
Journal: Blood (2017)
SP0157 The eular school of rheumatology. a challenging educational eular project. where are we now?
Authors: A. Iagnocco
Journal: Annals of the Rheumatic Diseases (2018)

EULAR has traditionally been a strong advocate of training and education in rheumatology, which has made EULAR the pre-eminent provider and facilitator of high-quality educational offerings for physicians, health professionals in rheumatology, and people with rheumatic and musculoskeletal diseases. Indeed, the international rheumatology community is set to benefit from high levels of education in rheumatology, with the aim of delivering significant relief to the lives of people with musculoskeletal and rheumatic diseases worldwide. In June 2017, the EULAR School of Rheumatology was launched at the Annual EULAR Congress. This is as a fully integrated operational entity contained within EULAR which combines all educational offers, whether they are live courses, online courses, books, webinars or any other material, under one roof. This new system has the aim of greatly facilitating access to all products, giving personalised overviews and allowing, for those who sign up for a membership, to use the various incentives and special offers. The School will also provide the members a secure means of storing their gained certifications and other personal information. In addition, members of the EULAR School of Rheumatology will be able to benefit from a new accumulative credit point system, which adds points according to educational hours spent in EULAR courses, either live or on-line. Members will also be regularly informed regarding the developments of the School and new educational and training materials. With the purpose of optimising and improving the already very solid educational offerings of EULAR, during the last two years, seven groups of eminent experts in education actively worked to develop new products to be added to the existing educational material of EULAR. Many different projects are currently being developed by these "classrooms" and are addressed to the whole rheumatology community (i.e. rheumatologists, undergraduates, trainees, teachers, researchers, health professionals, and people with rheumatic and musculoskeletal diseases). Indeed, in today's digital era, education and training possibilities are undergoing constant changes with new approaches, products and technologies coming up. Thus, the EULAR School of Rheumatology represents a model of future learning, reflecting the changing needs of the rheumatology community through offering new educational materials across this medical discipline and the greatest levels of access to the highest quality of education in the field. With the modern developments of the rheumatology discipline, EULAR School of Rheumatology is today taking its educational offerings, services and products to a global audience worldwide. For information about ongoing and new initiatives of the EULAR School of Rheumatology, please go to www.eular.org/school_of_rheumatology.cfm. <h3>Disclosure of Interest</h3> None declared
P105 Identification of rare coding variants in IL-1-related pathways in patients with adult-onset still’s disease
Authors: G Cavalli, R van Deuren, P Arts, M Steehouwer, P Sfriso, S Colafrancesco, R Priori, L Cantarini, E Baldissera, F van de Veerdonk, L Dagna, A Hoischen, CA Dinarello
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Assistant. <h3>Introduction</h3> Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease characterized by fever, arthritis, and multi-organ involvement. Inflammation in AOSD is mediated by interleukin (IL)-1β, as confirmed by the clinical efficacy of selective blockers. The genetic predisposition to this IL-1-driven inflammation remains nevertheless elusive. Previous studies failed to identify associations between polymorphisms in the IL-1 genes and AOSD, thus pointing at more complex genetic mechanisms. These cannot be investigated with traditional techniques for genetic partitioning, such as GWAS, which only assess common variants and polymorphisms. Studies focusing on highly penetrant rare variants or different types of mutations (i.e. small copy-number variations; insertions/deletions) are warranted. <h3>Objectives</h3> We hypothesized that genetically determined changes in IL-1-related pathways resulting in excessive IL-1β activity lead to the development of autoinflammation in AOSD. Scope of this study was to unravel the combined mutational variation of a network of IL-1-related receptors, pathways, counter-regulators, and cellular processes possibly involved in the pathogenesis of IL-1-mediated inflammation. <h3>Methods</h3> We collected clinical and genetic data from a large cohort of 76 AOSD patients and developed an innovative platform based on molecular inversion probes technology, which enables highly multiplexed targeted-resequencing of the coding sequence of 48 genes related to the IL-1-pathway, and allows studying rare and common variants in one assay. We have also screened 500 healthy controls, and 1000s of samples with other disorders using the same assay. <h3>Results</h3> We identified rare and unique (i.e. private variants) in the IL-1 pathway in several individuals with AOSD. Whether any of these are involved in a strong predisposition to AOSD is currently followed-up. Rare genetic variants have been identified in six IL-1-pathway 'clusters': Inflammasomes; IL–1 pathway; IL–1 family; IL–18 pathway; Autophagy; ROS production. <h3>Conclusions</h3> Unraveling the genetic bases of inflammation in AOSD deepens our understanding of the human innate immunome. This study platform may now serve for the genetic analysis of other IL-1-mediated conditions (i.e. gout and other autoinflammatory diseases), whose genetic predisposition remains elusive. Equally important, the identification of pathways amenable to targeting with small molecules or biologics may translate into remarkable clinical implications. <h3>Disclosure of Interest</h3> None declared.
Prevalence of clinically significant incidental findings by whole-body fludeoxyglucose F 18 positron emission tomography/computed tomography scanning in moderate-to-severe psoriasis patients participating in clinical trials
Authors: Marilyn T. Wan, Drew A. Torigian, Abass Alavi, Judith Alvarez, Zelma C. Chiesa Fuxench, Megan H. Noe, Maryte Papadopoulos, Daniel B. Shin, Junko Takeshita, Thomas J. Werner, Nehal N. Mehta, Joel M. Gelfand
Journal: Journal of the American Academy of Dermatology (2019)
THU0516 Efficacy and safety of vitamin d3 in patients with fibromyalgia. randomised, double blind, placebo-controlled trial
Authors: L.I. Lozano Plata, M.A. Garza Elizondo, D. Vega Morales, J.A. Esquivel Valerio, D.A. Galarza Delgado, K. Silva Luna, R. Díaz Niño de Rivera, A. Garza Guerra, G. Serna Peña, I. Hernández Galarza, L.E. Ramírez Monterrubio, J.P. Carrizales Luna
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> fibromyalgia (FM) is a disease characterised by widespread pain, sometimes fatigue, memory problems and sleep disturbances. It has been suggested that low blood levels of vitamin D correlate with increased pain scores in patients with FM. A recent meta-analysis indicated that vitamin D may decrease pain scores in patients with FM, but with a low quality trials. <h3>Objectives</h3> to assess the efficacy and safety of vitamin D3 in Fibromyalgia patients. <h3>Methods</h3> a 12 week randomised, double blind, placebo-controlled trial in eighty FM patients according to the criteria of the American College of Rheumatology (ACR) 2010 who were randomised into two groups, the treatment group (n=40) received 50,000 IU of oral vitamin D3 weekly, the second group (n=40) received placebo for 12 weeks. The primary outcome was to assess the change in the Spanish version of Fibromyalgia Impact Questionnaire (S-FIQ) and Visual Analogue Scale (VAS 0–10) from baseline to week 12. Baseline serum calcium levels were measured in all subjects. Vitamin D levels were measured by chemiluminescence considering normal ranges between 30 and 100 ng/ml, insufficiency between 10 and 30 ng/ml and deficiency less than 10 ng/ml, baseline and after 12 weeks. <h3>Results</h3> of the total, 61/80 (76%) had vitamin D insufficiency, 8/80 (10%) deficiency and 11/80 (14%) normal levels, the mean overall level of vitamin D was 21.2±9.0. There was no statistically significant reduction in S-FIQ scores in patients in the treatment group compared with placebo (47.0±23.3 vs 43.9±25.0, p=0.56) after 12 weeks; there was also no statistically significant decrease in VAS scores (6±5 vs 4±4.5, p=0.57). There was no improvement in the perception of pain when normalising vitamin D levels. No serious adverse events were reported in both groups. <h3>Table 1 Baseline characteristics</h3> <h3>Conclusions</h3> at 12 weeks of treatment with vitamin D3 50,000 IU versus placebo in patients with fibromyalgia had no statistically significant differences in the FIQ and VAS. It may be possible to find greater benefit from vitamin D if this period is extended. <h3>References</h3> [1] Clauw DJ. Fibromyalgia: a clinical review. JAMA2014; 311(15):1547–1555. [2] Yong WC, Sanguankeo A, Upala S. Effect of vitamin D supplementation in chronic widespread pain: a systematic review and meta-analysis. Clin Rheumatol2017Dec;36(12):2825–2833. <h3>Disclosure of Interest</h3> None declared
Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma
Authors: Bruno M. Grande, Daniela S. Gerhard, Aixiang Jiang, Nicholas B. Griner, Jeremy S. Abramson, Thomas B. Alexander, Hilary Allen, Leona W. Ayers, Jeffrey M. Bethony, Kishor Bhatia, Jay Bowen, Corey Casper, John Kim Choi, Luka Culibrk, Tanja M. Davidsen, Maureen A. Dyer, Julie M. Gastier-Foster, Patee Gesuwan, Timothy C. Greiner, Thomas G. Gross, Benjamin Hanf, Nancy Lee Harris, Yiwen He, John D. Irvin, Elaine S. Jaffe, Steven J. M. Jones, Patrick Kerchan, Nicole Knoetze, Fabio E. Leal, Tara M. Lichtenberg, Yussanne Ma, Jean Paul Martin, Marie-Reine Martin, Sam M. Mbulaiteye, Charles G. Mullighan, Andrew J. Mungall, Constance Namirembe, Karen Novik, Ariela Noy, Martin D. Ogwang, Abraham Omoding, Jackson Orem, Steven J. Reynolds, Christopher K. Rushton, John T. Sandlund, Roland Schmitz, Cynthia Taylor, Wyndham H. Wilson, George W. Wright, Eric Y. Zhao, Marco A. Marra, Ryan D. Morin, Louis M. Staudt
Journal: Blood (2019)
CDK6 coordinates JAK2V617F mutant MPN via NF-κB and apoptotic networks
Authors: Iris Z. Uras, Barbara Maurer, Harini Nivarthi, Philipp Jodl, Karoline Kollmann, Michaela Prchal-Murphy, Jelena D. Milosevic Feenstra, Markus Zojer, Sabine Lagger, Reinhard Grausenburger, Beatrice Grabner, Raimund Holly, Anoop Kavirayani, Christoph Bock, Heinz Gisslinger, Peter Valent, Robert Kralovics, Veronika Sexl
Journal: Blood (2019)
AB0740 Evaluation of hand dermal thickness and peripheral blood perfusion in systemic sclerosispatients
Authors: B. Ruaro, A. Sulli, T. Santiago, J.A. Pereira da Silva, C. Pizzorni, V. Tomatis, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is characterised by progressive skin involvement. The modified Rodnan Skin Score (mRSS) is the gold standard to asses skin damage, but it has significant limitations. Recently, several studies demonstrated the utility of skin high frequency ultrasound (US) as an alternative. <h3>Objectives</h3> The aim of this study was to identify possible correlations between peripheral blood perfusion (BP) and ultrasound dermal thickness (US-DT) at level of hand and finger in SSc patients. <h3>Methods</h3> Sixty-seven patients, satisfying the 2013 ACR/EULAR SSc criteria (mean age 64±9 SD years, mean disease duration 6±4 SD years) were enrolled. BP was measured as perfusion units (PU) by laser speckle contrast analysis (LASCA) at the level of dorsal region of hands, In a second time, different regions of interest (ROIs) were created at level of dorsum of the middle phalanx of 3rd finger and dorsum of hand bilaterally and the average BP was scored as perfusion units (PU), as previously reported.<sup>1,2</sup> Both skin high frequency US and mRSS were used to evaluate DT at the above mentioned skin sites.<sup>2</sup> The same examinations were performed in 65 healthy subjects. <h3>Results</h3> BP was negatively correlated with both US-DT (p=0.0005) and mRSS (p=0.007) in SSc patients at the finger sites, but not at the level of dorsum of the hands. In healthy subjects, there was no statistically significant correlation between BP and DT as evaluated by both US and mRSS at either skin sites. SSc patients showed a statistically significant lower BP at the finger sites than healthy subjects (p&lt;0.0001). No statistically significant difference in BP values was observed between SSc and healthy subjects at the dorsum of hand. <h3>Conclusions</h3> This study demonstrates a negative correlation between BP, as evaluated by LASCA and DT, as evaluated by both US and mRSS, in the 3rd finger of SSc patients. Additionally, the results confirm a reduced finger BP in SSc patients when compared to healthy subjects. <h3>Reference</h3> [1] Ruaro B, et al. Microvasc Res. 2017;115:28–33. [2] Ruaro B, et al. Ann Rheum Dis. 2014;73:1181–85. [3] Cutolo M, et al. Best Pract Res Clin Rheumatol. 2016;30:670–87. <h3>Disclosure of Interest</h3> None declared
Abstract 5507: <i>RAG1</i> high expression associated with <i>IKZF1</i> dysfunction in adult B-cell acute lymphoblastic leukemia
Authors: zheng Ge, Qi Han, Jinlong Ma, Yan Gu, Huihui Song, Malika Kapadia, Sinisa Dovat, Chunhua Song
Journal: Cancer Research (2018)

Abstract The recombination activating gene (RAG)-mediated recombination is the dominant mutational process and the predominant driver of oncogenic genomic rearrangement in acute lymphoblastic leukemia (ALL). This then leads to further leukemic clonal evolution. IKZF1 encodes a kruppel-like zinc finger protein, IKAROS that is essential for normal hematopoiesis and acts as a tumor suppressor in ALL. The genetic defects of a single IKZF1 allele are linked to the development of human ALL, characterized by an increased risk of relapses and poorer prognosis. We observed that RAG1 is significantly increased in subsets of B-ALL patients. High RAG1 expression correlates with high proliferation markers. IKAROS directly binds to the RAG1 promoter in B-ALL cells by quantitative chromatin-immunoprecipitation assay. IKAROS suppresses RAG1 promoter activity by luciferase reporter assay. Lentiviral IKAROS expression significantly suppresses RAG1 expression, but IKAROS shRNA promotes RAG1 expression in B-ALL cells. CK2 inhibitor by restoring IKAROS activity, significantly suppresses RAG1 expression in an IKAROS-dependent manner in B-ALL cells. RAG1 expression is significantly higher in patients with IKZF1 deletion, as compared to patients without IKZF1 deletion. Treatment with CK2 inhibitor also results in an increase in IKZF1 binding to the RAG1 promoter and suppression of RAG1 expression in primary B-ALL cells. Taken together, our results demonstrate that high expression of RAG1 correlates with high proliferation markers in B-ALL, and are the first to demonstrate that IKAROS directly suppresses RAG1 expression. Our data suggest RAG1 high expression works together with IKAROS dysfunction to drive oncogenesis of B-ALL, which have significance in an integrated prognostic model for adult ALL. Citation Format: zheng Ge, Qi Han, Jinlong Ma, Yan Gu, Huihui Song, Malika Kapadia, Sinisa Dovat, Chunhua Song. RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5507.
Abstract 17788: Repaired Coarctation is Associated With Central Hypertension, Increased Vessel Stiffness and Abnormal Wave Reflections - A Novel CMR Hemodynamics Study
Authors: Michael A Quail, Rebekah Short, Bejal Pandya, Jennifer A Steeden, Abbas Khushnood, Patrick Segers, Vivek Muthurangu
Journal: Circulation (2015)

Introduction: The basis of late cardiovascular mortality following coarctation repair is poorly understood. Although hypertension has been implicated, peripheral systolic pressure (pSBP) has not been shown to be definitively higher in this group. This may be because mortality is more related to central systolic pressure (cSBP) than pSBP. We have developed a novel cardiovascular magnetic resonance (CMR) protocol that allows assessment of cSBP and it components: resistance, compliance and wave reflections. The main aims of this study were i) characterize hemodynamic differences between patients and controls ii) define hemodynamic determinants of cSBP in patients and iii) Identify possible biomarkers amongst covariates associated with LV mass (LVM). Methods: 75 subjects, 50 patients with repaired coarctation, median age 23.5yrs (74% male) and 25 matched controls; 21.0yrs (72% male) were recruited. Ascending aorta area and flow waveforms were obtained using a high temporal resolution (10ms) spiral phase-contrast MR flow sequence. This data was used to derive cSBP and perform wave intensity analysis (WIA) non-invasively using previously validated techniques. The determinants of cSBP and LVM were assessed using multivariable linear regression analysis. Results: Central SBP was significantly higher in patients compared to controls (115±13 vs 107±9mmHg [mean±sd], p=0.002). However, there was only a trend towards higher pSBP (123±15 vs 117±11mmHg, p=0.052). Patients had reduced arterial compliance, increased characteristic impedance and larger backward compression waves (BCW) than controls; and these parameters were independently associated with cSBP. LVM index was significantly higher in patients than controls (73.1±14.6 vs 58.9±9.7g/m 2 , p=0.0001). Independent predictors of LVM included cSBP (p=0.001) and BCW (p=0.002), but importantly not pSBP or coarctation index. Conclusions: Non-invasive assessment of fundamental arterial hemodynamics by CMR is feasible. Using these techniques we have shown elevated cSBP in patients after coarctation repair. Elevated cSBP and BCW are important determinants of increased LVM following coarctation repair. These metrics represent superior biomarkers of afterload than coarctation index and pSBP.
Abstract MP090: Sleep Duration Predict Incident Obesity in Childhood and Adolescence: Meta-analysis of Prospective Studies
Authors: Michelle A Miller, Marlot Kruisbrink, Joanne Wallace, Andrew O’Keeffe, Sam Valint, Chen Ji, Francesco P Cappuccio
Journal: Circulation (2017)

Objectives: To assess the longitudinal evidence of a relationship between duration of sleep and both incidence of overweight and/or obesity and changes in body mass index in infants, children and adolescents. Methods: We performed a systematic search of publications using MEDLINE (1966-2016), EMBASE (from 1980), Web of Science (from 1945), the Cochrane Library and manual searches without language restrictions. Studies were included if they were prospective, had a follow up &gt;1 year, had measured duration of sleep at baseline and assessed either incident cases of overweight and/or obesity or changes in body mass index prospectively. Relative risks (RR), regression coefficients (beta) and 95% C.I. were extracted and pooled using a random effect model. Sensitivity analyses and meta-regressions were performed, heterogeneity and publication bias were also assessed. Results: Overall, 41 studies provided 56 independent cohort samples, including 98,130 boys and girls aged 0-18 years (follow-up 1 to 27 years). Sleep duration was assessed by questionnaire, either to parents or to children, actigraphy or polysomnography. Body mass index (BMI) was measured in all participants. In the pooled analyses, short duration of sleep was associated with a greater risk of becoming overweight or obese (RR: 1.57; 95% CI 1.34, 1.85; p&lt;10 -5 ; n=59,471). There was significant heterogeneity (I 2 =92%, p&lt;0.001), accounted for by three studies (I 2 =3% after their removal) and evidence of publication bias (p=0.007). The effect size increased with age (infants 1.40 [1.19, 1.65]; early childhood 1.53 [1.33, 1.76]; middle childhood 2.23 [2.18, 2.27]; adolescence 1.30 [1.11, 1.53]; p for heterogeneity &lt;10 -5 ). The effect was not associated with average length of follow-up (p=0.923) or quality (p=0.475). BMI decreased for every hour of increased sleep (pooled beta: -0.01; -0.03, 0.00 kg/m 2 per h, p=0.032; n=16,225). Conclusion: Short duration of sleep is a significant predictor of the development of overweight, obesity and weight gain from birth to adolescence.
Pooled Safety Analysis and Efficacy of Tenalisib (RP6530), a PI3Kδ/γ Inhibitor, in Patients with Relapsed/Refractory Lymphoid Malignancies
Authors: Swami P. Iyer, Auris Huen, Andres J M Ferreri, Bradley M. Haverkos, Jasmine M. Zain, Radhakrishnan Ramchandren, Mary Jo Lechowicz, Sumana Devata, Neil Korman, Lauren C. Pinter-Brown, Richard Delarue, Kasi V Routhu, Prajak Barde, Ajit M Nair, Carmelo Carlo-Stella
Journal: Blood (2018)
Am I Allergic to Penicillin?
Authors: Kimberly G. Blumenthal, Erica S. Shenoy
Journal: JAMA (2019)

Am I Allergic to Penicillin?Most patients who report allergies to penicillin are not allergic.Penicillin is one of the most commonly used antibiotics.Penicillin antibiotics are a large group of chemically related drugs that can be given by mouth or injection to treat many bacterial infections and are part of the group of drugs called beta-lactam antibiotics.Are Penicillin Allergies Common?
Effectiveness of a school-based physical activity intervention on adiposity, fitness and blood pressure: MOVI-KIDS study
Authors: Vicente Martínez-Vizcaíno, Diana P Pozuelo-Carrascosa, Jorge C García-Prieto, Iván Cavero-Redondo, Montserrat Solera-Martínez, Miriam Garrido-Miguel, Ana Díez-Fernández, Abel Ruiz-Hermosa, Mairena Sánchez-López
Journal: British Journal of Sports Medicine (2019)

Objective To test a physical activity intervention (MOVI-KIDS) on obesity indicators, physical fitness and blood pressure (BP) in children. Methods A crossover randomised cluster trial was conducted, which comprised 1434 children (4–7 years old) from 21 schools in the provinces of Cuenca and Ciudad Real in the Castilla-La Mancha region of Spain. The intervention consisted of three 60 min sessions/week on weekdays between October 2013 and May 2014. Changes in anthropometric variables, physical fitness and BP parameters were measured. The analyses used were mixed regression models to adjust for baseline covariates under cluster randomisation. Results There was no significant improvement in overweight/obesity with the intervention compared with the control group in both sexes. Further, the intervention did not alter other adiposity indicators or BP parameters. Improvements in cardiorespiratory fitness were seen in girls (1.19; 95% CI 0.31 to 2.08; p=0.008), but not in boys. Finally, there was an improvement in velocity/agility in both girls (−2.51 s; 95% CI −3.98 to −1.05; p=0.001) and boys (−2.35 s; 95% CI −3.71 to −0.98; p=0.001), and in muscular strength in both girls (0.66; 95% CI 0.03 to 1.28; p=0.038) and boys (1.26; 95% CI 0.03 to 1.28; p&lt;0.001). Conclusion MOVI-KIDS was not successful in reducing the adiposity and maintained BP levels at previous healthy values in children. The intervention, however, showed significant improvements in cardiorespiratory fitness in girls, and muscular strength and velocity/agility in boys and girls. Trial registration number NCT01971840 ; Post-results.