Medical Specialties Commons^™

Whole Exome Sequencing Identifies Novel Genes For Fetal Hemoglobin Response To Hydroxyurea In Children With Sickle Cell Anemia., V. A. Sheehan, J. R. Crosby, A. Sabo, N. A. Mortier, T. A. Howard, D. M. Muzny, S. Dugan-Perez, Banu Aygun, K. A. Nottage, J. M. Flanagan, +3 Additional Authors

Journal Articles

Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final …

A Pilot Academic-Community Partnership To Advance The D.C. Healthy Schools Act, Nisha Narayanan, Jonathan Tatum, Margarita Ramos, Jessica Kim, Nisha Punatar, Michele L. Mietus-Snyder

GW Research Days 2014

No abstract provided.

Mucopolysaccharidosis Iva (Morquio A Syndrome) And Vi (Maroteaux-Lamy Syndrome): Under-Recognized And Challenging To Diagnose, Ralph S. Lachman, Barbara K. Burton, Lorne A. Clarke, Scott Hoffinger, Shiro Ikegawa, Dong-Kyu Jin, Hiroki Kano, Ok-Hwa Kim, Christina Lampe, Nancy J. Mendelsohn, Renee Shediac, Pranoot Tanpaiboon, Klane K. White

Pediatrics Faculty Publications

OBJECTIVE:

Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux-Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI.

MATERIALS AND METHODS:

This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were …

Gauging Regional Differences In The Hiv Prevalence Rate Among Injection Drug Users In The U.S., Jichuan Wang, Brian Kelly

Pediatrics Faculty Publications

This article aims to introduce and demonstrate the application of the standardization and decomposition analysis (SDA) method to gauge differences in HIV prevalence rates among injection drug users (IDUs) across regions (Northeast, South, Midwest, and West) in the U.S. Using the SDA, the regional HIV prevalence rates were standardized and a rate difference between regions was decomposed into component effects, such as the “real” rate difference, and component effects attributed to differences in specific compositions of confounding factors. A total of 9,824 injection drug users (IDUs) retrieved from the national database of the National Institute on Drug Abuse’s Cooperative Agreement …

Superresolution Imaging Of Human Cytomegalovirus Vmia Localization In Sub-Mitochondrial Compartments, Shivaprasad Bhuvanendran, Kyle Salka, Kristen Rainey, Sen Chandra Sreetama, Elizabeth Williams, Margretha Leeker, Vidhya Prasad, Jonathan Boyd, George H. Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Pediatrics Faculty Publications

The human cytomegalovirus (HCMV) viral mitochondria-localized inhibitor of apoptosis (vMIA) protein, traffics to mitochondria-associated membranes (MAM), where the endoplasmic reticulum (ER) contacts the outer mitochondrial membrane (OMM). vMIA association with the MAM has not been visualized by imaging. Here, we have visualized this by using a combination of confocal and superresolution imaging. Deconvolution of confocal microscopy images shows vMIA localizes away from mitochondrial matrix at the Mitochondria-ER interface. By gated stimulated emission depletion (GSTED) imaging, we show that along this interface vMIA is distributed in clusters. Through multicolor, multifocal structured illumination microscopy (MSIM), we find vMIA clusters localize away from …

Perinatal Pharmacology, Karel M. Allegaert, V. Fanos, John N. Van Den Anker, Stephanie L. Läer

Pediatrics Faculty Publications

No abstract provided.

Rheumatic Heart Disease In Uganda: The Association Between Mhc Class Ii Hla Dr Alleles And Disease: A Case Control Study, Emmy Okello, Andrea Z. Beaton, Charles Mondo, Paul Kruszka, Noah Kiwanuka, Richard Odoi-Adome, Juergen Freers

Pediatrics Faculty Publications

Background

Rheumatic heart disease (RHD), the only long term consequence of acute rheumatic fever, remains a leading cause of morbidity and mortality among young adults in Uganda. An inherited susceptibility to acute rheumatic fever centers around the major histocompatibility class II human leucocyte antigens. However, there is paucity of data from sub-Saharan Africa. This study compares the frequency of HLA class II DR alleles between RHD cases and normal controls in Uganda.

Methods

One hundred ninety-nine participants including 96 established RHD cases aged 5–60 years and 103 age and sex matched normal controls were recruited for participation. DNA was manually …

Preface Of The Special Issue: “Recent Cmv Research”, Kayla Dufrene, Roberta L. Debiasi, Anamaris M. Colberg-Poley

Pediatrics Faculty Publications

No abstract provided.

Expression Of A Secreted Fibroblast Growth Factor Binding Protein-1 (Fgfbp1) In Angioproliferative Kaposi Sarcoma, Patricio E. Ray, Ali Al-Attar, Xue-Hui Liu, Jharna R. Das, Elena Tassi, Anton Wellstein

Pediatrics Faculty Publications

Objective: Kaposi’s sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGFbinding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the …

Children's Hospital Association Consensus Statements For Comorbidities Of Childhood Obesity, Elizabeth Estrada, Ihuoma Eneli, Sarah Hampl, Michele L. Mietus-Snyder, Nazrat Mirza, Erinn Rhodes, Brooke Sweeney, Lydia Tinjaero-Deck, Susan J. Woolford, Stephen J. Pont

Pediatrics Faculty Publications

Background: Childhood obesity and overweight affect approximately 30% of US children. Many of these children have obesity-related comorbidities, such as hypertension, dyslipidemia, fatty liver disease, diabetes, polycystic ovary syndrome (PCOS), sleep apnea, psychosocial problems, and others. These children need routine screening and, in many cases, treatment for these conditions. However, because primary care pediatric providers (PCPs) often are underequipped to deal with these comorbidities, they frequently refer these patients to subspecialists. However, as a result of the US pediatric subspecialist shortage and considering that 12.5 million children are obese, access to care by subspecialists is limited. The aim of this …

Working Together For Global Health Goals: The United States Agency For International Development And Faith-Based Organizations, Clydette L. Powell

Pediatrics Faculty Publications

For many years, and before the term “FBO” was used for faith-based organizations, the United States Agency for International Development (USAID) has supported the work of FBOs in global health and development. The Agency has long recognized the impact of FBOs within that development space, because these organizations are often well positioned to reach the hard-to-reach and to go the last mile because of their strong ties to the community. Moreover, FBOs deliver a substantial percentage of the health services in some developing countries. Faith partners, whether Catholic, Protestant, Buddhist, Hindu, Muslim, or other, have an important role to play …

Proposed Guidelines For The Diagnosis And Management Of Methylmalonic And Propionic Acidemia., Matthias R Baumgartner, Friederike Hörster, Carlo Dionisi-Vici, Goknur Haliloglu, Daniela Karall, Kimberly A. Chapman, +19 Additional Authors

Pediatrics Faculty Publications

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100'000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA …

Aspirin Use And Knowledge In The Community: A Population- And Health Facility Based Survey For Measuring Local Health System Performance., Gregory A Roth, Catherine W. Gillespie, Ali A Mokdad, Danny D Shen, David W Fleming, Andy Stergachis, Christopher J L Murray, Ali H Mokdad

Pediatrics Faculty Publications

BACKGROUND: Little is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.

METHODS: The Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for …

Immunologic Special Forces: Anti-Pathogen Cytotoxic T-Lymphocyte Immunotherapy Following Hematopoietic Stem Cell Transplantation, Michael Keller, Catherine M. Bollard

Pediatrics Faculty Publications

Anti-pathogen adoptive T-cell immunotherapy has been proven to be highly effective in preventing or controlling viral infections following hematopoietic stem cell transplantation. Recent advances in manufacturing protocols allow an increased number of targeted pathogens, eliminate the need for viral transduction, broaden the potential donor pool to include pathogen-naïve sources, and reduce the time requirement for production. Early studies suggest that anti-fungal immunotherapy may also have clinical benefit. Future advances include further broadening of the pathogens that can be targeted and development of T-cells with resistance to pharmacologic immunosuppression.

Critical Periods Of Increased Fetal Vulnerability To A Maternal High Fat Diet, M. D. Plata, L. Williams, Y. Seki, K. Hartil, H. Kaur, C. L. Lin, A. Fiallo, A. S. Glenn, E. B. Katz, P. M. Vuguin, +2 Additional Authors

Journal Articles

Background: Fetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression. Methods: Female wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, …

Evpedia: A Community Web Portal For Extracellular Vesicles Research, D. K. Kim, J. Lee, S. R. Kim, D. S. Choi, Y. J. Yoon, J. H. Kim, G. Go, L. Blanc, S. Sahoo, Y. S. Gho, +85 Additional Authors

Journal Articles

MOTIVATION: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. RESULTS: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 …

Exploiting Pre-Rrna Processing In Diamond Blackfan Anemia Gene Discovery And Diagnosis, J. E. Farrar, P. Quarello, R. Fisher, K. A. O'Brien, A. Aspesi, S. Parrella, E. Atsidaftos, A. Vlachos, J. M. Lipton, S. R. Ellis, +9 Additional Authors

Journal Articles

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in …

In Utero Exposure To A Maternal High-Fat Diet Alters The Epigenetic Histone Code In A Murine Model, M. A. Suter, J. Ma, P. M. Vuguin, K. Hartil, A. Fiallo, R. A. Harris, M. J. Charron, K. M. Aagaard

Journal Articles

OBJECTIVE: Data from animal models show that in utero exposure to a maternal high-fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. …

P53-Independent Cell Cycle And Erythroid Differentiation Defects In Murine Embryonic Stem Cells Haploinsufficient For Diamond Blackfan Anemia-Proteins: Rps19 Versus Rpl5, S. A. Singh, T. A. Goldberg, A. L. Henson, S. Husain-Krautter, A. Nihrane, L. Blanc, S. R. Ellis, J. M. Lipton, J. M. Liu

Journal Articles

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome caused by ribosomal protein haploinsufficiency. DBA exhibits marked phenotypic variability, commonly presenting with erythroid hypoplasia, less consistently with non-erythroid features. The p53 pathway, activated by abortive ribosome assembly, is hypothesized to contribute to the erythroid failure of DBA. We studied murine embryonic stem (ES) cell lines harboring a gene trap mutation in a ribosomal protein gene, either Rps19 or Rpl5. Both mutants exhibited ribosomal protein haploinsufficiency and polysome defects. Rps19 mutant ES cells showed significant increase in p53 protein expression, however, there was no similar increase in the …

Second-Line Immunosuppressive Treatment Of Childhood Nephrotic Syndrome: A Single-Center Experience, J. Kim, N. Patnaik, N. Chorny, R. Frank, L. Infante, C. Sethna

Journal Articles

OBJECTIVE: Most cases of idiopathic nephrotic syndrome in childhood are responsive to corticosteroids. However, there is a small group of children that demonstrate steroid resistance (steroid-resistant nephrotic syndrome; SRNS), steroid dependence, or that frequently relapse (frequent-relapse steroid-sensitive nephrotic syndrome; FR-SSNS) which are more clinically difficult to treat. Therefore, second-line immunosuppressants, such as alkylating agents, calcineurin inhibitors, antimetabolites and, more recently, rituximab, have been used with varying success. The objective was to evaluate the response rates of various second-line therapies in the treatment of childhood nephrotic syndrome. STUDY DESIGN: A retrospective chart review of pediatric subjects with idiopathic nephrotic syndrome was …

X-Linked Agammaglobulinemia Presenting As Polymicrobial Pneumonia, Including Pneumocystis Jirovecii, A. M. Jongco, J. D. Gough, K. Sarnataro, D. W. Rosenthal, J. Moreau, P. Ponda, V. R. Bonagura

Journal Articles

No abstract provided.

Anti-Inflammatory Actions Of Endogenous And Exogenous Interleukin-10 Versus Glucocorticoids On Macrophage Functions Of The Newly Born, K. Kasat, H. Patel, O. Predtechenska, I. Vancurova, D. Davidson

Journal Articles

OBJECTIVE: To determine whether specific macrophage immune functions of the newly born are insensitive to the actions of therapeutic levels of dexamethasone (DEX), previously measured in infants with bronchopulmonary dysplasia (BPD), compared with betamethasone (BETA) and exogenous or endogenous interleukin-10 (IL-10). STUDY DESIGN: Macrophages were differentiated from cord blood monocytes (N=18). A serial dose-response (around 10(-8)M), in vitro study was used to examine the effect of DEX, BETA and IL-10, on proinflammatory (PI) cytokine release, phagocytosis and respiratory burst. RESULT: Exogenous IL-10 (10(-8)M) significantly (P < 0.05) inhibited the endotoxin-stimulated release of IL-6, IL-8 and tumor necrosis factor by 63 to 82% with no significant effect by DEX and BETA. There was no inhibition by these three agents at 10(-8)M on phagocytosis and respiratory burst. Inhibition of endogenous IL-10 with a monoclonal antibody significantly increased endotoxin-stimulated cytokine release by at least fourfold. CONCLUSION: Macrophages were relatively insensitive to therapeutic levels of DEX and BETA with regard to PI cytokine release. This study provides rationale for translational and preclinical research using airway instillation of IL-10 for the treatment of BPD.

Bisphenol A Exposure Is Associated With Decreased Lung Function, A. J. Spanier, E. K. Fiorino, L. Trasande

Journal Articles

Objective To examine the associations of bisphenol A (BPA) exposure with lung function measures and exhaled nitric oxide (FeNO) in children. Study design We performed a cross-sectional analysis of a subsample of US children age 6-19 years who participated in the 2007-2010 National Health and Nutrition Examination Survey. We assessed univariate and multivariable associations of urinary BPA concentration with the predicted pulmonary function measures for age, sex, race/ethnicity and height (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], forced expiratory flow 25%-75%, and FEV1 divided by FVC) and with FeNO. Results Exposure and outcome data were available …

Blood Pressure Variability In Children With Primary Vs Secondary Hypertension, D. Leisman, M. Meyers, J. Schnall, N. Chorny, R. Frank, L. Infante, C. B. Sethna

Journal Articles

Increased blood pressure variability (BPV) is correlated with adverse cardiovascular (CV) events in adults. However, there has been limited research on its effect in the pediatric population. Additionally, BPV differences between primary and secondary hypertension (HTN) are not known. Children with primary and secondary HTN underwent 24-hour ambulatory blood pressure monitoring and echocardiography studies. BPV measures of standard deviation (SD), average real variability (ARV), and range were calculated for the 24-hour, daytime, and nighttime periods. Seventy-four patients (median age, 13.5 years; 74% boys) were examined, 40 of whom had primary HTN. Body mass index z score and age were independent …

Characteristics Of Avoidant/Restrictive Food Intake Disorder In Children And Adolescents: A "New Disorder" In Dsm-5, M. M. Fisher, D. S. Rosen, R. M. Ornstein, K. A. Mammel, D. K. Katzman, E. S. Rome, S. T. Callahan, J. Malizio, S. Kearney, B. T. Walsh

Journal Articles

Purpose: To evaluate the DSM-5 diagnosis of Avoidant/Restrictive Food Intake Disorder (ARFID) in children and adolescents with poor eating not associated with body image concerns. Methods: A retrospective case-control study of 8e18-year-olds, using a diagnostic algorithm, compared all cases with ARFID presenting to seven adolescent-medicine eating disorder programs in 2010 to a randomly selected sample with anorexia nervosa (AN) and bulimia nervosa (BN). Demographic and clinical information were recorded. Results: Of 712 individuals studied, 98 (13.8%) met ARFID criteria. Patients with ARFID were younger than those with AN (n = 98) or BN (n = 66), (12.9 vs. 15.6 vs. …

Decreased Langerhans Cell Responses To Il-36 Gamma: Altered Innate Immunity In Patients With Recurrent Respiratory Papillomatosis, J. Devoti, L. Hatam, A. Lucs, A. Afzal, A. Abramson, B. M. Steinberg, V. Bonagura

Journal Articles

Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease caused by human papillomaviruses (HPVs) types 6 and 11 that is characterized by the polarization of adaptive immune responses that support persistent HPV infection. Respiratory papillomas express elevated mRNA levels of IL-36 gamma, a proinflammatory cytokine in comparison to autologous clinically normal laryngeal tissues; however there is no evidence of inflammation in these lesions. Consistent with this, respiratory papillomas do not contain T(H)1-like CD4(+) T-cells or cytotoxic CD8(+) T-cells, but instead contain a predominance of T(H)2-like and T regulatory cells (Tregs). In addition, papillomas also are infiltrated with immature Langerhans cells …

Helping The Community From The Bottom Up: Distributing Diapers To The Williamsburg Community, Constance A. Hull, Caroline Kelsey

VA Engage Journal

There is a great need for a sustainable supply of clean diapers for low-income residents of Williamsburg since this region is without a diaper bank. Being unable to afford diapers can have a myriad of negative consequences from being unable to send children to child care to increased health risks involved in leaving a baby in a soiled diaper. Our model of a diaper bank differs from most because we mail diapers directly to families, eliminating transportation needs. We hope to partner with community agencies and The College of William & Mary to expand our services and create a more …

Diagnosis And Treatment Of Pediatric Acquired Aplastic Anemia (Aaa): An Initial Survey Of The North American Pediatric Aplastic Anemia Consortium (Napaac), D. A. Williams, C. Bennett, A. Bertuch, M. Bessler, T. Coates, S. Corey, Y. Dror, J. Lipton, A. Vlachos, A. Shimamura, +7 Additional Authors

Journal Articles

BackgroundRandomized clinical trials in pediatric aplastic anemia (AA) are rare and data to guide standards of care are scarce. ProcedureEighteen pediatric institutions formed the North American Pediatric Aplastic Anemia Consortium to foster collaborative studies in AA. The initial goal of NAPAAC was to survey the diagnostic studies and therapies utilized in AA. ResultsOur survey indicates considerable variability among institutions in the diagnosis and treatment of AA. There were areas of general consensus, including the need for a bone marrow evaluation, cytogenetic and specific fluorescent in situ hybridization assays to establish diagnosis and exclude genetic etiologies with many institutions requiring results …

The Treatment-Naive Microbiome In New-Onset Crohn's Disease, D. Gevers, S. Kugathasan, L. A. Denson, Y. Vazquez-Baeza, W. Van Treuren, B. Y. Ren, E. Schwager, D. Knights, J. Markowitz, R. J. Xavier, +22 Additional Authors

Journal Articles

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with …

Randomized, Double-Blind, Placebo-Controlled Trial Of The Efficacy And Safety Of Rilonacept In The Treatment Of Systemic Juvenile Idiopathic Arthritis, N. T. Ilowite, K. Prather, Y. Lokhnygina, L. E. Schanberg, M. Elder, D. Milojevic, J. W. Verbsky, S. J. Spalding, B. S. Gottlieb, C. I. Sandborg, +12 Additional Authors

Journal Articles

OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. METHODS: An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in >/=2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by …