tbuckley/cabot-search huggingface dataset:
Trends in Obesity Among Participants Aged 2–4 Years in the Special Supplemental Nutrition Program for Women, Infants, and Children — United States, 2000–2014
Authors: Liping Pan, David S Freedman, Andrea J Sharma, Karen Castellanos-Brown, Sohyun Park, Ray B Smith, Heidi M Blanck
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Childhood obesity is associated with negative health consequences in childhood (1) that continue into adulthood (2), putting adults at risk for type 2 diabetes, cardiovascular disease, and certain cancers (1). Obesity disproportionately affects children from low-income families (3). Through a collaboration with the United States Department of Agriculture (USDA), CDC has begun to use data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Participants and Program Characteristics (WIC PC) to replace the Pediatric Nutrition Surveillance System (PedNSS) (4,5) for obesity surveillance among young children from low-income families. CDC examined trends in obesity prevalence during 2000-2014 among WIC participants aged 2-4 years using WIC PC data. Overall obesity prevalence increased from 14.0% in 2000 to 15.5% in 2004 and 15.9% in 2010, and then decreased to 14.5% in 2014. During 2010-2014, the prevalence of obesity decreased significantly overall, among non-Hispanic whites, non-Hispanic blacks, Hispanics, American Indian/Alaska Natives and Asians/Pacific Islanders, and among 34 (61%) of the 56 WIC state agencies in states, the District of Columbia, and U.S. territories. Despite these declines, the obesity prevalence among children aged 2-4 years in WIC remains high compared with the national prevalence of 8.9% among children aged 2-5 years in 2011-2014. Continued initiatives to work with parents and other stakeholders to promote healthy pregnancies, breastfeeding, quality nutrition, and physical activity for young children in multiple settings are needed to ensure healthy child development.
SP0019 Histone Modification and Osteoarthritis
Authors: S. Monteagudo
Journal: Annals of the Rheumatic Diseases (2016)

Epigenetic mechanisms, processes that alter gene expression without changes in DNA sequence, precisely regulate gene expression by dynamic remodeling of chromatin. Eukaryotic DNA is wrapped around a histone octamer (H3/H4 heterotetramer and two H2A/H2B dimers) to form the nucleosome, the fundamental building block of chromatin. Histone proteins are subject to covalent modifications that modulate the local structure of chromatin and influence gene expression by regulating the accessibility of gene loci to transcriptional machinery. The dynamic remodeling of chromatin through histone modifications by nuclear proteins including histone acetyltransferases, deacetylases, and methyltransferases, as well as by demethylases, modulate spatiotemporal gene expression during cartilage development, homeostasis and disease.  Disruptor of telomeric silencing 1-like (DOT1L) is the main histone-modifying enzyme that catalyzes the methylation on lysine-79 of histone 3 (H3K79). The human protein DOT1L contains 1537 aminoacids, with its N-terminal part responsible for the methyltransferase activity. The remaining C-terminal part is involved in physical interactions with many transcription relevant proteins. The general function of DOT1L is to methylate H3K79 as a member of a large protein complex, which can influence the transcriptional state. DOT1L9s histone methyltransferase activity has been linked to active transcription, and plays a role in many biological processes including the DNA damage response, the cell cycle, embryonic development and cell reprogramming. In cancer biology, DOT1L is involved in MLL-rearranged leukemia and in other tumors. We reported a strong genetic association between polymorphisms in the human DOT1L gene and hip cartilage thickness as well as osteoarthritis (OA). Variations in the DOT1L gene are also associated with human height. Furthermore, we earlier demonstrated that silencing of Dot1L inhibited chondrogenic differentiation of murine progenitor cells. Interestingly, DOT1L-associated H3K79 methylation has been linked to the Wingless-type (Wnt) cascade. Gain and loss of function studies for Wnt signaling mediator beta-catenin or Wnt antagonists such as Frizzled related protein have demonstrated that tight regulation of this pathway is key to joint health. This could specifically identify DOT1L as an attractive target for joint diseases, more particularly for OA. DOT1L is an enzyme and, thus, can be pharmacologically modulated.  We therefore hypothesized that DOT1L plays a major role in cartilage homeostasis by tightly regulating gene expression patterns of key signaling pathways, such as the Wnt cascade. New insights into the transcriptional mechanisms may contribute to the development of new epigenetics-based strategies for the treatment of joint diseases, adding a new way to modulate fundamental signaling pathways in joint disease and repair.  Disclosure of Interest  S. Monteagudo Grant/research support from: Marie Curie Fellowship
Regions on Chromosomes 1 and 14 Are Associated with VWF:Ag Levels in African Americans Using Mapping By Admixture Linkage Disequilibrium
Authors: Andrew D Paterson, Nicole M Roslin, Pamela A. Christopherson, Daniel B Bellissimo, Veronica H Flood, Sandra L. Haberichter, Robert R Montgomery, Zimmerman Program Investigators
Journal: Blood (2014)
PTU-154 HMGB1 As a Prognostic Biomarker in The Progression of Barrett’s Oesophagus
Authors: R Porter, R Murray, GI  , R Petty, EM El-Omar, GL Hold, MH McLean
Journal: Gut (2016)

<h3>Introduction</h3> Barrett’s oesophagus (BO) is metaplasia from normal squamous to mucin secreting columnar epithelium. BO is a precursor of neoplastic progression to dysplasia and adenocarcinoma, with no associated progression biomarker available. High Mobility Group Box-1 (HMGB1) is a ubiquitous nuclear protein that regulates gene expression. When phosphorylated, it translocates to the cytoplasm and extracellular space to stimulate pro-inflammatory responses and influence epithelial cell behaviour. Our aim was to assess expression of HMGB1 in BO and neoplastic progression. <h3>Methods</h3> Epithelial nuclear and cytoplasmic subcellular expression of HMGB1 was assessed immunohistochemically in endoscopically retrieved paraffin embedded biopsies sourced from the Grampian Biorepository (n = 155 total). Ethical approval was granted by the Grampian biorepository scientific committee. A gastrointestinal pathologist (GIM) confirmed histological diagnosis. 18, 25, 78 and 13 biopsies were assessed, from 11 patients with normal oesophageal mucosa, 14 patients with normal gastric mucosa, 20 patients with non-dysplastic BO and 9 patients with dysplastic BO, respectively. Also included were 12 biopsies (7 patients) and 9 biopsies (6 patients) from non-dysplastic BO associated with progression to dysplasia and adenocarcinoma, respectively. Intensity of HMGB1 staining was double scored as none, weak, moderate or strong immunopositivity. Analysis used Fisher’s exact test of 2X2 contingency tables. <h3>Results</h3> HMGB1 was expressed in the nuclei in all groups. Normal oesophageal biopsies expressed no or weak cytoplasmic HMGB1. Non-dysplastic (p &lt; 0.0001) and dysplastic (p &lt; 0.0001) BO epithelium expressed stronger cytoplasmic HMGB1 compared to both normal oesophageal and gastric epithelium. Dysplastic BO expressed increased HMGB1 in both nuclear (p = 0.0003) and cytoplasmic (p = 0.0002) compartments compared to non-dysplastic BO. Background non-dysplastic BO in those that had progressed to dysplasia had increased nuclear HMGB1 compared to non progressors (p = 0.015). Background non-dysplastic BO in those who progressed to cancer expressed less cytoplasmic HMGB1 compared to non progressors (p = 0.0118). Non-dysplastic and dysplastic BO epithelium had clear foci of absent nuclear HMGB1 expression in areas of moderate/strong cytoplasmic HMGB1 expression. <h3>Conclusion</h3> There was evidence of dynamic subcellular localisation of HMGB1 expression in association with BO and dysplasia. Cytoplasmic HMGB1 expression may be a novel biomarker to aid diagnosis and predict progression of BO. The functional significance of this warrants further investigation. <h3>Disclosure of Interest</h3> None Declared
Efficacy and Safety of Topical Sirolimus Therapy for Facial Angiofibromas in the Tuberous Sclerosis Complex
Authors: Mari Wataya-Kaneda, Ayumi Nakamura, Mari Tanaka, Misa Hayashi, Shoji Matsumoto, Koji Yamamoto, Ichiro Katayama
Journal: JAMA Dermatology (2016)

Inhibitors of mammalian target of rapamycin complex 1, such as sirolimus, effectively target skin lesions in tuberous sclerosis complex (TSC). However, systemic treatment causes adverse effects, and topical sirolimus has shown promise in the treatment of facial angiofibromas.To evaluate the efficacy, safety, and optimal concentration of a topical sirolimus gel vs placebo for treatment of facial angiofibromas in TSC.A double-blind, placebo-controlled, parallel-group, dose-escalation, phase 2 randomized clinical trial using 3 sirolimus gel concentrations was performed at Osaka University Hospital, Osaka, Japan. Thirty-six patients with TSC and facial angiofibromas, including 18 aged 3 to 18 years (children) and 18 aged 19 to 65 years (adults), were enrolled from December 10, 2013, to July 17, 2014. Analysis was by intention to treat.The adult and child groups were each subdivided into 3 groups (n = 12 each) and randomized to receive sirolimus gel concentrations of 0.05%, 0.1%, or 0.2% or placebo using a web-response system in a 2:1 fashion. The medication was applied to the patient's lesions twice per day for 12 weeks. Each patient underwent assessment at 2, 4, 8, and 12 weeks during treatment and at 4 weeks after discontinuation of the treatment (16 weeks).The primary end point, planned before starting data collection, was an improvement factor, represented as a variable composed of tumor size reduction and a lessening of the redness of the 3 target tumors at 12 weeks relative to baseline.All 36 patients (13 male and 23 female; median age, 40 years; range, 6-47 years) completed the study analyses. The improvement factor was statistically significant in all active treatment groups receiving 0.2% sirolimus (mean [SD], 1.94 [0.68]; P < .001) and not in the adult subgroups receiving 0.1% (mean [SD], 0.88 [0.85]; P = .31) and 0.05% (mean [SD], 1.63 [1.11]; P = .09) concentrations of sirolimus. No significant adverse effects were observed. Mild skin dryness (13 patients [36%]) and irritation (11 patients [31%]) were observed. Low blood levels of sirolimus (<0.25 ng/mL) were detected in adults (1 patient [25%] in the 0.1% adult subgroup and 2 patients [50%] in the 0.2% adult subgroup) and particularly in children (1 patient [25%] in the 0.05% child subgroup, 2 patients [50%] in the 0.1% child subgroup, and 4 patients [100%] in the 0.2% child subgroup).Topical sirolimus gel is safe and effective for facial angiofibromas in TSC. The optimal concentration of sirolimus was 0.2%.umin.ac.jp Identifier: UMIN000012420.
FRI0500 Idiopathic Granulomatous Mastitis: A Single Center Experience
Authors: M. Cinar, S. Yilmaz, M. Cakar, S. Pay
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of the breast. Difficulties can be experienced in the treatment of IGM due to the lack of a common consensus in the literature. Treatment options include corticosteroids, surgical treatment, immunosuppressive drugs and conservative treatment with antibiotics. <h3>Objectives</h3> To present our experience about patients with IGM on immunosuppressive therapy. <h3>Methods</h3> The data of patients with a diagnosis of IGM under immunosuppressive therapy followed in the rheumatology outpatient clinic of a tertiary center enrolled between September 2010 and August 2015 were evaluated retrospectively. 16 histopathologically diagnosed patients receiving immunosuppressive therapy were evaluated for their treatments and treatment responses. <h3>Results</h3> The mean age of the patients, the average duration of immunosuppressive therapy and the average follow-up period were 35.9±6.5 years, 19.6±14.1 months and 28.3±17.8 months, respectively. Initially, 15 patients received (93.8%) steroids and methotrexate, and 1 patient (6.2%) was treated only with steroids. All patients responded well to initial therapy. Eight (53.3%) patients achieved remission with steroid + methotrexate. 2 of the other 7 patients relapsed after discontinuation of steroids and 1 after discontinuation of steroid + methotrexate. A positive response was obtained after the restart of treatment with steroids and methotrexate in these patients. Of these 7 patients, no recurrence was observed in 3 (42.9%) patients with only methotrexate and in 4 (57.1%) patients in the maintenance treatment with steroids and methotrexate. Lowered dose of steroid was associated with recurrence during follow-up of the patient taking only steroids as the initial treatment. 5 patients (33.3%) taking methotrexate had drug side effects, not necessitate stopping the treatment. <h3>Conclusions</h3> Systemic immunosuppressive therapy is safe and effective in IGM. Azathioprine and methotrexate have been the most frequently used immunosuppressive drugs in the literature. Our experience with methotrexate-based regimen allows the rapid reduction of the steroid dose and leads to remission. <h3>References</h3> Konan A, Kalyoncu U, Dogan I, Kiliç YA, Karakoç D, Akdogan A, Kiraz S, Kaynaro Lu V, Onat D. Combined long-term steroid and immunosuppressive treatment regimen in granulomatous mastitis. Breast Care (Basel). 2012 Aug;7(4):297–301. Sheybani F, Sarvghad M, Naderi HR, Gharib M. Treatment for and clinical characteristics of granulomatous mastitis.Obstet Gynecol. 2015 Apr;125(4):801–7. <h3>Disclosure of Interest</h3> None declared
Mixed (Umbilical Cord Blood And Bone Marrow) Transplantation in Thalassaemia: An Experience from Eastern India
Authors: Subhasish Dey, Pinaki Gupta, Sushil Biswas, Ujjal Kanti Roy, Somnath Datta, Ashis Mukhopadhyay, Soma Mukhopadhyay
Journal: Blood (2008)
OP0222 Pregnancy Outcome in Patients Affected by Juvenile Idiopathic Arthritis (JIA) Exposed To Biological Agents: A Monocentric Experience in A Tertiary Centre of Milan
Authors: I. Pontikaki, M. Gerosa, L.M. Argolini, L. Trespidi, P.L. Meroni
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> During the last sixteen years, biologics have been used in our centre in an open prospective study for the treatment of refractory JIA not only in paediatric age but also in young adults. <h3>Objectives</h3> To underline the capability to become pregnant, not negatively influenced by biologics and to describe the pregnancy outcome of our young patients who got pregnant during the biologics treatment, since this event seems to be facilitated from a low disease activity under biologics. <h3>Methods</h3> Seventeen women affected by refractory JIA became pregnant during biologic therapy. Two males affected by JIA, both treated with Adalimumab have been achieved as indirect pregnancies. All patients had a long lasting refractory polyarticular disease not responsive to DMARDs. Patients were treated with biological agents like Etanercept (9 patients), Adalimumab (4 patients), Golimumab (3 patients), Infliximab (1 patient) and Rituximab (2 patients) as monotherapy and most of the cases after multiple switches. <h3>Results</h3> 3 patients decided for an elective termination; 16 patients had a normal pregnancy resulted in live born infants, full term, with no structural abnormalities and still in good health. The median time of exposure to biologics was 48 months (min 10- max 72 months). No abnormalities were achieved neither in the live born infants nor in the fetuses of the pregnancies which ended with an elective termination. The paternal exposure did not influence conception and was not associated with negative outcome of pregnancy. <h3>Conclusions</h3> The availability of therapies like antiTNFa and other biologics has raised important questions about pregnancy outcome in female and male patients affected by JIA exposed to biologics. Other data regarding limited populations affected by Crohn9s disease or Rheumatoid Arthritis treated with antiTNFa have been published. It doesn9t seem to be an increased risk to pregnancy loss. Even if there is no increase in miscarriage or malformation or birth defect, as reported in letterature, TNFa inhibitors are raccomended to be discontinued after pregnancy detection. In our experience no complications or unexpected side effects on the course of pregnancy were observed. <h3>Disclosure of Interest</h3> None declared
Prognostic Value of Immunophenotyping of Multiple Myeloma: A Study on 685 Patients Uniformly Treated with High-Dose Therapy.
Authors: Gema Mateo, Maria A. Montalban, Maria-Belén Vidriales, Juan J. Lahuerta, Maria-Victoria Mateos, Norma C. Gutiérrez, Laura Rosiñol, Laura Montejano, Ma Consuelo López-Berges, Joan Bladé, Rafael Martínez, Javier de la Rubia, Joaquín Diaz-Mediavilla, Anna Sureda, José M. Ribera, José M. Ojanguren, Felipe de Arriba, Luis Palomera, Ma José Terol, Santiago Gardella, Alberto Orfao, J.F. San Miguel
Journal: Blood (2007)
Eculizumab Protects Against TE and Prolongs Survival in Patients with Paroxysmal Nocturnal Hemoglobinuria: An International PNH Registry Study
Authors: Gérard Socié, Hubert Schrezenmeier, Petra Muus, Jeffrey Szer, Alvaro Urbano-Ispizua, Jaroslaw P. Maciejewski, Robert A. Brodsky, Monica Bessler, Yuzuru Kanakura, Wendell F. Rosse, Gus Khursigara, Camille L. Bedrosian, Peter Hillmen
Journal: Blood (2012)
PWE-158 Is Manometry Fit for Purpose in Predicting Response to Sphincterotomy in Type 2 and 3 Sphincter of Oddi Dysfunction - A Tertiary Centres Experience Including A Novel Use of Botulinum Toxin
Authors: J Geraghty, R Cox, T Begum, A Makin
Journal: Gut (2016)

<h3>Introduction</h3> The latest Rome III revision of the Milwaukee classification describes 3 types of Sphincter of Oddi dysfunction (SOD). Type 1 is biliary-type pain, abnormal LFTs (&gt;2 times upper limit of normal on ≥2 occasions) and a dilated bile duct (&gt;8 mm). Type 2 is pain and either laboratory or imaging abnormalities and type 3 is pain alone. Type 1 is usually successfully treated with endoscopic sphincterotomy (ES), while Types 2 and 3 respond less consistently and Sphincter of Oddi manometry (SOM) is used to preselect those likely to benefit. There are however concerns with SOM. It is difficult to interpret, time consuming, expensive and associated with a high risk of pancreatitis - this applies to both the solid state and water perfused system, which we used. From 2007 to 2013, our unit performed SOM on type 2 and 3 patients. In 2014, our practice changed to quadrantic ampullary injections of botulinum toxin (100 U) to paralyse the SOD and allow assessment of the response. If clinical improvement persisted to 3 months, a further injection was given. Following two successful responses, ES was performed. Our aim was to assess the safety and efficacy of the two approaches. <h3>Methods</h3> 50 patients were studied retrospectively - 34 were evaluated with SOM and 16 with botulinum. <h3>Results</h3> 94.2% of patients were female and 76.9% had a prior cholecystectomy. 25 patients were Type 2 and 27 Type 3. In the SOM group (n = 34), 20 patients had high baseline or high frequency contractions and underwent ES. In this group 40% (n = 8) developed pancreatitis post procedure. In 5 patients SOM was normal and no ES was performed, with the pancreatitis rate being 40% (n = 2). In 9 patients technical problems prevented SOM being performed. Instead, these patients had ES, with the pancreatitis rate being 22.2%. Overall the intention to treat pancreatitis rate for SOM was 35.3%. Overall, this group required 149 bed days, with a median stay of 1 day (range 0–20). Three months following SOM; 77.3% had an improvement in symptoms compared to 45.5% at 12 months. In the botulinum group (n = 16), there were 25 injections and no cases of pancreatitis were reported, a significantly lower rate than SOM (p = 0.005). One patient developed abdominal pain requiring a four day admission. Four patients had no response and had medical manangement instigated for functional disease. The remaining patients are proceding through the management algorithm. <h3>Conclusion</h3> SOM, has a high risk of pancreatitis and following ES a modest response rate. The risks and cost do not support this strategy and so new management algorithms are required. Our pilot data suggests twice repeated botulinum injection is a safe investigative procedure and worthy of examination in larger trials. <h3>Disclosure of Interest</h3> None Declared
Low Dose Oral Fludarabine Plus Cyclophosphamide in Elderly Patients with Untreated and Refractory Chronic Lymphocytic Leukemia.
Authors: Francesco Forconi, F. Toraldo, E. Sozzi, M. Lenoci, A. Fabbri, A. Gozzetti, M. Tassi, D. Raspadori, Francesco Lauria
Journal: Blood (2007)
RUNX1/AML1 Mutants Collaborate with BMI1 in the Development of Myelodysplastic Syndromes (MDS) / Acute Myeloid Leukemia (AML) in a Mouse BMT Model.
Authors: Hironori Harada, Daichi Inoue, Noriko Doki, Ye Ding, Yuka Harada, Toshio Kitamura
Journal: Blood (2012)
Confocal Microscopy Is Useful for Detection of Bortezomib Related Neuropathy (BOR-PN) in Multiple Myeloma (MM) Patients (PTS)
Authors: Federica Cocito, Silvia Mangiacavalli, Gabriella Ricciardelli, Virginia Ferretti, Roberto Ceccuzzi, Mario Cazzola, paolo Emilio Bianchi, Alessandro Corso
Journal: Blood (2014)
Inverse Correlation of Early Regulatory T Cell Reconstitution Post-Transplant and Acute and Chronic Graft-Versus-Host-Disease.
Authors: Katayoun Rezvani, Stephan Mielke, Yasemin Kilical, Bipin Savani, Keyvan Keyvanfar, Nancy Hensel, Roger Kurlander, A. John Barrett
Journal: Blood (2005)