tbuckley/cabot-search huggingface dataset:
Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy
Authors: Cassie N Kline, Nancy M Joseph, James P Grenert, Jessica van Ziffle, Eric Talevich, Courtney Onodera, Mariam Aboian, Soonmee Cha, David R Raleigh, Steve Braunstein, Joseph Torkildson, David Samuel, Michelle Bloomer, Alejandra G de Alba Campomanes, Anuradha Banerjee, Nicholas Butowski, Corey Raffel, Tarik Tihan, Andrew W Bollen, Joanna J Phillips, W Michael Korn, Iwei Yeh, Boris C Bastian, Nalin Gupta, Sabine Mueller, Arie Perry, Theodore Nicolaides, David A Solomon
Journal: Neuro-Oncology (2016)

Molecular profiling is revolutionizing cancer diagnostics and leading to personalized therapeutic approaches. Herein we describe our clinical experience performing targeted sequencing for 31 pediatric neuro-oncology patients.We sequenced 510 cancer-associated genes from tumor and peripheral blood to identify germline and somatic mutations, structural variants, and copy number changes.Genomic profiling was performed on 31 patients with tumors including 11 high-grade gliomas, 8 medulloblastomas, 6 low-grade gliomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal ganglioneuroma, 1 choroid plexus carcinoma, 1 chordoma, and 1 high-grade neuroepithelial tumor. In 25 cases (81%), results impacted patient management by: (i) clarifying diagnosis, (ii) identifying pathogenic germline mutations, or (iii) detecting potentially targetable alterations. The pathologic diagnosis was amended after genomic profiling for 6 patients (19%), including a high-grade glioma to pilocytic astrocytoma, medulloblastoma to pineoblastoma, ependymoma to high-grade glioma, and medulloblastoma to CNS high-grade neuroepithelial tumor with BCOR alteration. Multiple patients had pathogenic germline mutations, many of which were previously unsuspected. Potentially targetable alterations were identified in 19 patients (61%). Additionally, novel likely pathogenic alterations were identified in 3 cases: an in-frame RAF1 fusion in a BRAF wild-type pleomorphic xanthoastrocytoma, an inactivating ASXL1 mutation in a histone H3 wild-type diffuse pontine glioma, and an in-frame deletion within exon 2 of MAP2K1 in a low-grade astrocytic neoplasm.Our experience demonstrates the significant impact of molecular profiling on diagnosis and treatment of pediatric brain tumors and confirms its feasibility for use at the time of diagnosis or recurrence.
Maturation by Toll Like Receptor Ligand R848 Improves the Uptake of Apoptotic Leukemic Cells by Monocyte Derived Dendritic Cells.
Authors: Willemijn van den Ancker, Theresia M Westers, Hetty J Bontkes, Tanja D de Gruijl, Gert J Ossenkoppele, Arjan A van de Loosdrecht
Journal: Blood (2009)
Incidence and Characteristics of Infections Following Cord Blood Stem Cell Transplantation in Children.
Authors: Y.J. Lim, Y.H. Lee, H.H. Koo, K.H. Yoo, KW Sung, NG Chung, B. Cho, H.K. Kim, H.J. Kang, H.Y. Shin, H.S. Ahn, H. Kook, T.J. Hwang, H.N. Moon, J.J. Seo, H.J. Im, S.K. Park, Thad T. Ghim, J.O. Hah, C.J. Lyu, J.E. Park, K.C. Lee, Y.T. Lim, J.Y. Lim, I.J. Kang
Journal: Blood (2007)
Soluble Lymphotoxin Plays a Critical Role in Acute Graft-Versus-Host Disease
Authors: Kate A Markey, Angela C Burman, Rachel D Kuns, Edward S Morris, Tatjana Banovic, Neil C Raffelt, Stuart D Olver, Christian R Engwerda, Heinrich Korner, Kelli P A MacDonald, Geoff R Hill
Journal: Blood (2008)
Hematopietic Cell Transplantation after a Low-Dose, Total-Body Irradiation Based Regimen in Elderly Patients with AML: A Multicenter, Multinational, Prospective HOVON/SAKK/OSHO Study.
Authors: Dietger Niederwieser, Jan Cornelissen, Haifa-Kathrin Al-Ali, Leo Verdonck, Rainer Krahl, Alois Gratwohl, Claudia Nehring, Cornelia Becker, Wolfram Poenisch, Thoralf Lange, Rainer Storb, Bob Lowenberg
Journal: Blood (2006)
SAT0057 Low Mortality Rate in A Cohort of Rheumatoid Arthritis Patients from South Italy
Authors: D. Iacono, G. Cuomo, V. D'Abrosca, I. Pantano, G. Valentini
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder associated with increased mortality (1), (standardized mortality ratio for all causes–SMR, being 1.47 in the last 50 years) (2). <h3>Objectives</h3> To investigate the mortality rate and predictive factors as assessed at admission in a cohort of RA patients followed at a South Italy tertiary centre. <h3>Methods</h3> RA patients admitted to the outpatient Clinic of a tertiary centre from 01/01/2008 to 31/12/2015 were investigated. Table 1 shows patients features (age, sex, disease duration, Simplified Disease Activity Index-SDAI index, Health Assessment Questionnaire-Disability Index-HAQ-DI, Rheumatoid Factor-RF and/or Anti-Citrullinated Cyclic Peptides Antibody-ACPA, concomitant comorbidity) as detected at baseline, and treatment during follow-up. RA patients mortality incidence rate (event/100person year) was calculated, baseline predictors of mortality were analyzed by univariate and multivariate cox-regression analysis. <h3>Results</h3> A total of 608 RA patients were included (497 women), median age 56.8 years, range 15–89.5. On December 31 2015, 589 out of patient were alive, 19 were known to have died and 7,3% had been lost to follow up. Mortality Incidence rate (MIR) in our cohort was 0.79 deaths/100 person-year, SMR with respect to Italian population was 0.79 (MIR in Italy 1/100 person-year). This feature might depend on the low prevalence of RF/ACPA positivity (69.13%) in our series. Cox regression analysis (univariate analysis) pointed out age at first visit (HR 1.14; p≤0.0001), diabetes (HR 4.395; p=0.004) and a HAQ value&gt;1 (HR 6.02; p=0.02) as independent predictors of mortality. On the contrary, female sex resulted to have a protective role (HR 0.349, p=0.027). At multivariate analysis, the only baseline independent predictor of mortality was age at admission (HR 1.17, 95% CI 1.01–1.35, p=0.026). <h3>Conclusions</h3> The present study points out a South Italian RA SMR lower than that in general Italian population and significantly lower than that reported in RA patients from other countries (2). This result can depend on the lower percentage of RF/ACPA positive patients in our cohort in respect to general population. Epidemiological studies on the sierological profile of South Italian RA patients are needed. <h3>References</h3> Sokka T et al. ClinExpRheumatol. 2008;26(Suppl):S35–61. Dadoun S et al. Joint Bone Spine. 2013;80:29–33. <h3>Disclosure of Interest</h3> None declared
AB0160 MIR-155 Facilitate The Differentiation of TH17 Cell by Inhibiting The Gene Expression of ETS-1 in Vitro/in Vivo Experiments
Authors: Z. Ye, Z. Yin, X. Luo, X. Chen, W. He
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> MicroRNA (miR) as a class of regulatory elements are plays important role in various autoimmune diseases, including rheumatoid arthritis.MiR-155 has been demonstrated as a central regulator of the autoimmune system, but its function during autoimmune arthritis is still poorly understood. <h3>Objectives</h3> To clarify the function of miR-155 in CD4<sup>+</sup>regulatory Th17 cell differentiation, as well as the mechanism involved in autoimmune arthritiTo clarify the function of miR-155 in CD4<sup>+</sup>regulatory Th17 cell differentiation, as well as the mechanism involved in autoimmune arthritis. <h3>Methods</h3> In vitro, CD4<sup>+</sup> cell was isolated from DAB1 mice9 spleen. We performed gain-and-loss-of-function analysis by transfection miR-155 mimics and miR-155 inhibitors into purified CD4+T cells. Also, we used RNA interference to silence Ets-1 gene expression. In addition, in vivo, up regulation of miR-155 expression by lent virus miR-155 (LV-miR-155) infection and silencing of miR-155 expression by lent virus-anti-miR-155 (LV-anti-miR-155) was researched in the experimental mice with type II collagen (CII)-induced arthritis (CIA). The ratio of IL-17 was analyzed using flow cyctometry (FCM).The related gene expression such as Foxp3, RORgt, IFN-g, Ets-1and stat3 was detected by Quantitative Real-time PCR (qPCR) and western blotting. <h3>Results</h3> The result showed that miR-155 promoted Th17 cell differentiation. It also induced related gene expression, such as Foxp3, RORgt, IFN-g and stat3; it inhibited Ets-1 gene expression. This may because miR-155 modulates Th-17 cell differentiation by targeting Ets-1.Here we identify miR-155 was highly correlated with disease in mice with experimental CIA. In vivo over expression of miR-155 led to more Th-17cells and severe CIA, and the related genes were higher express, but Ets-1 was lower expression. In contrast, the down regulation of miR-155 expression resulted in fewer Th17 cells and Normal mice. The related genes were lower express, but Ets-1 was higher expression. <h3>Conclusions</h3> Our data show a critical role for miR-155 in Th17 differentiation and the pathogenesis of autoimmune arthritis, and it might be involved in the occurrence and development of autoimmune diseases in rheumatoid arthritis. <h3>Disclosure of Interest</h3> None declared
FRI0086 Before Clinically Detectable Arthritis Develops, ACPA-Positive and ACPA-Negative Arthralgia Patients Have Different Symptoms
Authors: L.E. Burgers, H.W. van Steenbergen, L. Mangnus, T.W.J. Huizinga, A.H.M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis (RA) have different genetic risk factors and underlying biological mechanisms. Therefore, we hypothesized that patients9 characteristics in the symptomatic phase before clinical arthritis has emerged are also different. We investigated this by studying the arthralgia phase of ACPA-positive and ACPA-negative patients. <h3>Methods</h3> Patients included in a clinically suspect arthralgia (CSA)-cohort were followed for 2 years or until arthritis development. At inclusion, information on initial symptoms and current symptoms was obtained, physical examination and MRI performed and blood samples taken. A comparison was made between ACPA-positive and ACPA-negative CSA-patients that later developed arthritis. <h3>Results</h3> 35 patients (17-ACPA-positive, 18 ACPA-negative) included between April 2012 and May 2015 developed arthritis. 88% of ACPA-negative patients experienced morning stiffness as an initial symptom, compared to 40% of ACPA-positive patients (p=0.01). ACPA-positive patients more often had symptoms in both upper and lower extremities than ACPA-negative patients (35% versus 6%, p=0.03). Important reasons for rheumatologists to identify CSA was morning stiffness in ACPA-negative patients (38% versus 7%, p=0.04) and inflammatory-type arthralgia in ACPA-positive patients (67% versus 19%, p=0.01). ACPA-positive patients had a longer symptom duration at first presentation (median of 22.4 weeks versus 10.6 weeks, Figure 1) but converted to arthritis quicker (median 6.9 versus 15.9 weeks after inclusion, p=0.04, Figure 1). A combination of variables clustered ACPA-positive and ACPA-negative patients in PLS-analysis. <h3>Conclusions</h3> In the phase preceding clinical arthritis, ACPA-negative and ACPA-positive arthralgia patients have different characteristics. This contributes to the notion that ACPA-positive and ACPA-negative RA are different disease subsets. <h3>Acknowledgement</h3> The research leading to these results was funded by a Vidi-grant of the Netherlands Organisation for Scientific Research, a grant of the Dutch Arthritis Foundation, a grant of the Dutch Organization of Health Research and the FP7 grant TEAM. <h3>Disclosure of Interest</h3> None declared
OP0107 Teriparatide and Denosumab Combination Therapy and Skeletal Metabolism
Authors: A. Fassio, D. Gatti, O. Viapiana, V. Braga, L. Idolazzi, G. Adami, M. Rossini
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Despite therapeutic options for osteoporosis have greatly expanded over the past few decades, the treatment of patients with established severe osteoporosis still remains challenging. Recently the combined teriparatide (TPD) and denosumab therapy was shown to increase bone mineral density (BMD) more than either agent alone. <h3>Objectives</h3> The aim of this study was to compare the changes in bone turnover markers and in inhibitors of the Wnt canonical pathway in patients treated with either denosumab alone or TPD alone or when TPD was added to patients previously treated with denosumab. <h3>Methods</h3> Open label prospective randomized study, involving 59 women over 65 years old affected by severe postmenopausal osteoporosis (with the evidence of at least two moderate-severe vertebral fractures), Bone turnover markers C-terminal telopeptide of type I collagen (CTX) and intact N-propeptide of type I collagen ad (P1NP) and inhibitors of the Wnt canonical pathway sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) were evaluated. <h3>Results</h3> In the groups treated with TPD or with denosumab alone bone turnover markers rose and decreased, respectively. In TPD group a later significant increase in DKK1 was observed, while in denosumab group a progressive increase in SOST was associated with a progressive significant decrease in DKK1. In the group treated first with denosumab and in which TPD was added 3 months later, the rounded values of both CTX and P1NP increased 3 months after the beginning of TPD by approximately the same absolute and percentage value of the group of patients treated with TPD alone, showing that the strong effect of denosumab on bone turnover is easily reversed by TPD treatment. In this group, SOST increased as in the denosumab alone group, while DKK1 progressively increased as in the TPD alone group. <h3>Conclusions</h3> In conclusion, in this study we showed that TPD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST, suggesting that the Wnt signalling pathway is not involved in the positive bone balance seen in the combination TPD-denosumab group. <h3>Disclosure of Interest</h3> None declared
EBV-Associated Post-Transplant Lymphoproliferative Disorder after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Keon Hee Yoo, Hee-Jin Kim, Chang Seok Ki, Ki Woong Sung, Hye Lim Jung, Young Hyeh Ko, Hong-Hoe Koo
Journal: Blood (2007)
Vicarious contagion decreases differentiation – and comes with costs
Authors: Ovul Sezer, Michael I. Norton
Journal: Behavioral and Brain Sciences (2016)

Abstract Baumeister et al. propose that individual differentiation is a crucial determinant of group success. We apply their model to processes lying in between the individual and the group – vicarious processes. We review literature in four domains – attitudes, emotions, moral behavior, and self-regulation – showing that group identification can lead to vicarious contagion, reducing individual differentiation and inducing negative consequences.
AB0865 Vitamin D Receptor Polymorphisms Are Not Associated with The Risk of Kawasaki Disease (KD) in A Group of Italian Children
Authors: F. Falcini, F. Marini, S. Stagi, D. Rigante, G. Lepri, M. Matucci-Cerinic, M.L. Brandi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Kawasaki disease (KD) is an acute multisystemic vasculitis, affecting primarily infants and children, and it is the most common cause of acquired heart disease in Western countries. The exact pathogenesis of KD has not been clearly identified, but infections caused by one or more pathogens are strongly suspected as major cause of the disease. Our previous study demonstrated that KD patients have highly reduced 25(OH)-vitamin D levels in comparison with healthy controls and also with other immunological disorders, suggesting a hypothetical role of vitamin D deficiency in the development of coronary artery damage in KD, and low vitamin D levels might contribute to the severity of chronic vascular abnormalities. Specific polymorphisms of vitamin D receptor (<i>VDR</i>) gene have recently been associated with different biologic response to vitamin D itself. <h3>Objectives</h3> 1.To analyze the possible associations of these polymorphisms in a series of Italian children affected by KD. 2. To evaluate a possible influence of VDR polymorphism in enhancing the risk of the disease. <h3>Methods</h3> We recruited 50 Italian infants and children affected by typical KD (38 males, 12 females), age ranging from 2 through to 62 months. Genomic DNA was extracted from peripheral blood leukocytes to analyze <i>VDR</i> polymorphisms by PCR-based sequencing (<i>CDX2</i> in the promoter region) and PCR-based enzymatic digestions (<i>FokI</i> in exon 2, <i>BsmI</i> and <i>ApaI</i> in intron 8, and <i>TaqI</i> in exon 9). An Italian population of 2221 unrelated individuals without KD or other immunological disorders was used as healthy controls. The distribution of polymorphism genotypes and alleles was evaluated in patients vs healthy controls. <h3>Results</h3> The distribution of all Cdx2, <i>FokI, BsmI, ApaI</i>, and <i>TaqI</i> polymorphisms (both as genotypes or alleles) did not show significant differences between affected subjects and healthy controls. <h3>Conclusions</h3> In conclusion, this pilot study evidence that <i>VDR</i> polymorphisms seem not to have any influence in determining the risk of KD. Anyway, future larger studies are needed to unravel the exact relationship between <i>VDR</i> genotype and KD development and/or clinical characteristics. <h3>Disclosure of Interest</h3> None declared
CDC Grand Rounds: Family History and Genomics as Tools for Cancer Prevention and Control
Authors: Juan L. Rodriguez, Cheryll C. Thomas, Greta M. Massetti, Debra Duquette, Lindsay Avner, John Iskander, Muin J. Khoury, Lisa C. Richardson
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Although many efforts in cancer prevention and control have routinely focused on behavioral risk factors, such as tobacco use, or on the early detection of cancer, such as colorectal cancer screening, advances in genetic testing have created new opportunities for cancer prevention through evaluation of family history and identification of cancer-causing inherited mutations. Through the collection and evaluation of a family cancer history by a trained health care provider, patients and families at increased risk for a hereditary cancer syndrome can be identified, referred for genetic counseling and testing, and make informed decisions about options for cancer risk reduction (1). Although hereditary cancers make up a small proportion of all cancers, the number of affected persons can be large, and the level of risk among affected persons is high. Two hereditary cancer syndromes for which public health professionals have worked to reduce the burden of morbidity and mortality are hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome.
Results from the Phase I Portion of a Phase I/II Study of ATN-224 and Bortezomib for Patients with Multiple Myeloma Relapsed from or Refractory to Bortezomib
Authors: James R. Berenson, Thomas Ervin, Ralph V. Boccia, Olcay Batuman, Regina Swift, Christina DiLauro Abaya, Andrew P. Mazar, Gilad S. Gordon, Steven D. Reich, Jennifer A. Callahan
Journal: Blood (2008)
FRI0177 Time To Achieve Remission Predicts Long Term Survival of Low-Dose Etanercept: An Observational Study: Table 1.
Authors: F. Ometto, B. Raffeiner, C. Botsios, L. Friso, D. Astorri, L. Bernardi, L. Punzi, A. Doria
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To investigate survival of low-dose etanercept (ETN) (25 mg weekly) and possible predictors. <h3>Methods</h3> We collected retrospectively data of RA patients starting ETN between April 2001 and September 2014 who achieved and maintained low-dose ETN for at least 12 months. Patients were evaluated every 3 months. Patients who achieved and maintained remission (DAS28 &lt;2.6) for at least 6 months started low dose ETN. If remission was lost <i>in two consecutive visits</i> the patient returned to full dose. We recorded the time to achieve remission (TTR), the time in which ETN dose was reduced since remission (TRL) and the time in which patients returned to full dose or were switched to other biologics. Variables collected are reported in Table I. Survival was analysed with Cox-regression. <h3>Results</h3> Among 532 patients, 276 were excluded because of missing data or because they were lost from follow-up leaving 256 patients eligible. After 11.28±4.05 years, 151/256 (59.0%) maintained half dose (Table 1). TTR, and TRL were associated to low-dose failure (Table 1) and correlated with each other (TTR and TRL R 0.45, p&lt;0.001). We run two separate analyses for TTR and TRL, covariates were positive rheumatoid factor or anti-citrullinated peptides and mean prednisone dose. TTR was a significant predictor of low-dose failure (OR 1.50 per year increase, 95% C.I. 1.34–1.68, p&lt;0.001) while TRL was not (Table 2). <h3>Conclusions</h3> A shorter TTR is a predictor of long-term survival of low-dose ETN. <h3>Disclosure of Interest</h3> None declared
“One Hour” Rituximab Infusion Is Safe and Improves Patient Care and Outpatient Unit Management.
Authors: Thérèse Aurran-Schleinitz, Gwaenaelle Gravis, Martine Vittot, Diane Coso, Jérôme Rey, Jean-Marc Schiano, Aude Charbonnier, Emmanuelle Fougereau, Dominique Maraninchi, Reda Bouabdallah
Journal: Blood (2005)
Abdominal pain after colonoscopy
Authors: Joseph Dalby Sinnott, David C Howlett
Journal: BMJ (2016)

A 43 year old woman was admitted to the surgical assessment unit with increasing abdominal pain 36 hours after a colonoscopy and polypectomy. On examination her abdomen was tender and mildly distended. Computed tomography (CT) was performed (fig 1⇓). What is the diagnosis?



Fig 1  Computed tomography scan of abdomen



The CT shows free air in the abdomen, which is indicative of a perforated bowel. Clips …
Cytokine Patterns and Lymphocyte Subsets in Patients with Chronic GVHD after Allogeneic Stem Cell Transplantation with Reduced Intensity Conditioning.
Authors: Cristina C. Skert, Daniela D. Damiani, Francesca F. Patriarca, Angela A. Michelutti, Carla C. Fili, Patrizia P. Lucchi, Michele M. Malagola, Cesare C. Bergonzi, Aldo A. Roccaro, Doris D. Ricotta, Luigi L. Caimi, Renato R. Fanin, Domenico D. Russo
Journal: Blood (2007)
G01 : Liraglutide is effective in the histological clearance of non-alcoholic steatohepatitis in a multicentre, doubleblinded, randomised, placebo-controlled phase II trial
Authors: M.J. Armstrong, P. Gaunt, G.P. Aithal, R. Parker, D. Barton, D. Hull, K. Guo, G. Abouda, M. Aldersley, S.C. Gough, J.W. Tomlinson, R.M. Brown, S.G. Hübscher, P.N. Newsome
Journal: Journal of Hepatology (2015)
Neurotoxicity of Bortezomib Therapy in Multiple Myeloma (MM): A Single Center Experience.
Authors: Ashraf Badros, Jay S. Dalal, Olga Goloubeva, Jenni Thompson, Kelly Yager, Can Ilyas, Aaron P. Rapoport, Robert G. Fenton, Gorgun Akpek, Saul Yanovich, Edward Sausville
Journal: Blood (2006)
CCL2 is a KIT D816V–dependent modulator of the bone marrow microenvironment in systemic mastocytosis
Authors: Georg Greiner, Nadine Witzeneder, Angelika Berger, Klaus Schmetterer, Gregor Eisenwort, Ana-Iris Schiefer, Simone Roos, Theresia Popow-Kraupp, Leonhard Müllauer, Johannes Zuber, Veronika Sexl, Lukas Kenner, Wolfgang R. Sperr, Peter Valent, Matthias Mayerhofer, Gregor Hoermann
Journal: Blood (2016)