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Burns and kawasaki

Martin Prince Alphonse, Trang T Duong, Chisato Shumitzu, Truong Long Hoang, Brian W McCrindle, Alessandra Franco, Stéphane Schurmans, Dana J Philpott, Martin L Hibberd, Jane Burns, Taco W Kuijpers, Rae S M Yeung
Kawasaki disease (KD) is a multisystem vasculitis that predominantly targets the coronary arteries in children. Phenotypic similarities between KD and recurrent fever syndromes point to the potential role of inflammasome activation in KD. Mutations in NLRP3 are associated with recurrent fever/autoinflammatory syndromes. We show that the KD-associated genetic polymorphism in inositol-triphosphate 3-kinase C (ITPKC) (rs28493229) has important functional consequences, governing ITPKC protein levels and thereby intracellular calcium, which in turn regulates NLRP3 expression and production of IL-1β and IL-18...
September 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Kevin G Friedman, Kimberly Gauvreau, Akiko Hamaoka-Okamoto, Alexander Tang, Erika Berry, Adriana H Tremoulet, Vidya S Mahavadi, Annette Baker, Sarah D deFerranti, David R Fulton, Jane C Burns, Jane W Newburger
BACKGROUND: The natural history of coronary artery aneurysms (CAA) after intravenous immunoglobulin (IVIG) treatment in the United States is not well described. We describe the natural history of CAA in US Kawasaki disease (KD) patients and identify factors associated with major adverse cardiac events (MACE) and CAA regression. METHODS AND RESULTS: We evaluated all KD patients with CAA at 2 centers from 1979 to 2014. Factors associated with CAA regression, maximum CA z-score over time (zMax), and MACE were analyzed...
September 15, 2016: Journal of the American Heart Association
Margery A Connelly, Chisato Shimizu, Deborah A Winegar, Irina Shalaurova, Ray Pourfarzib, James D Otvos, John T Kanegaye, Adriana H Tremoulet, Jane C Burns
BACKGROUND: Glycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses...
2016: BMC Pediatrics
Andrew S Zeft, Jane C Burns, Rae S Yeung, Brian W McCrindle, Jane W Newburger, Samuel R Dominguez, Marsha S Anderson, Cammon Arrington, Stanford T Shulman, Jeein Yoon, Helen Tewelde, Carter Mix, C Arden Pope
OBJECTIVE: To analyze associations of short-term exposure to fine particulate matter (diameter ≤ 2.5 µm [PM2.5]), a measurable component of urban pollution, with the event date of fever onset for patients with Kawasaki disease (KD) residing in 7 metropolitan regions. STUDY DESIGN: A case-crossover study design was used. Time trends, seasonality, month, and weekday were controlled for by matching. We assembled PM2.5 exposure measurements from urban monitors and imputed PM2...
October 2016: Journal of Pediatrics
Shiying Hao, Bo Jin, Zhou Tan, Zhen Li, Jun Ji, Guang Hu, Yue Wang, Xiaohong Deng, John T Kanegaye, Adriana H Tremoulet, Jane C Burns, Harvey J Cohen, Xuefeng B Ling
OBJECTIVE: To develop and validate a novel decision tree-based clinical algorithm to differentiate Kawasaki disease (KD) from other pediatric febrile illnesses that share common clinical characteristics. STUDY DESIGN: Using clinical and laboratory data from 801 subjects with acute KD (533 for development, and 268 for validation) and 479 febrile control subjects (318 for development, and 161 for validation), we developed a stepwise KD diagnostic algorithm combining our previously developed linear discriminant analysis (LDA)-based model with a newly developed tree-based algorithm...
September 2016: Journal of Pediatrics
John C Whitin, Tom To-Sang Yu, Xuefeng Bruce Ling, John T Kanegaye, Jane C Burns, Harvey J Cohen
BACKGROUND: Kawasaki disease (KD) is an acute vasculitis in children that can cause coronary artery abnormalities. Its diagnosis is challenging, and many cytokines, chemokines, acute phase reactants, and growth factors have failed evaluation as specific biomarkers to distinguish KD from other febrile illnesses. We performed protein profiling, comparing plasma from children with KD with febrile control (FC) subjects to determine if there were specific proteins or peptides that could distinguish the two clinical states...
2016: PloS One
Anita J Campbell, Jane C Burns
Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries.(1,2) The primary goal of treatment is to prevent coronary artery aneurysms (CAA). Between 10 and 20% of KD patients are resistant to treatment with intravenous immunoglobulin (IVIG) and have an almost nine-fold increased risk of developing CAA.(3) In addition, approximately 80-90% of patients who go on to develop CAA have abnormal coronary artery dimensions on their first echocardiogram and can therefore be identified as high-risk patients...
July 5, 2016: Journal of Infection
Masao Komeda, Masaji Arai, Kazuo Tamai, Kozo Kawasaki
We have developed a new silicon irradiation holder with a neutron filter to increase the irradiation efficiency. The neutron filter is made of an alloy of aluminum and B4C particles. We fabricated a new holder based on the results of design analyses. This filter has limited use in applications requiring prolonged use due to a decrease in the amount of (10)B in B4C particles. We investigated the influence of (10)B reduction on doping distribution in a silicon ingot by using the Monte Carlo Code MVP.
July 2016: Applied Radiation and Isotopes
Adriana H Tremoulet, Sonia Jain, Susan Kim, Jane Newburger, Moshe Arditi, Alessandra Franco, Brookie Best, Jane C Burns
BACKGROUND: Although Kawasaki disease (KD) is the most common cause of acquired heart disease in children and may result in coronary artery aneurysms (CAA) with an attendant risk of myocardial infarction, there is no recommended therapy to halt progression of arterial wall damage and prevent aneurysm formation in the acute phase of the vasculitis. While intravenous immunoglobulin (IVIG) reduces the risk of CAA, up to 20% of KD patients are IVIG resistant and have a higher risk for developing CAA...
May 2016: Contemporary Clinical Trials
Jane W Newburger, Masato Takahashi, Jane C Burns
Kawasaki disease is an acute, self-limited vasculitis of unknown etiology that occurs predominantly in infants and children. If not treated early with high-dose intravenous immunoglobulin, 1 in 5 children develop coronary artery aneurysms; this risk is reduced 5-fold if intravenous immunoglobulin is administered within 10 days of fever onset. Coronary artery aneurysms evolve dynamically over time, usually reaching a peak dimension by 6 weeks after illness onset. Almost all the morbidity and mortality occur in patients with giant aneurysms...
April 12, 2016: Journal of the American College of Cardiology
John B Gordon, Lori B Daniels, Andrew M Kahn, Susan Jimenez-Fernandez, Matthew Vejar, Fujito Numano, Jane C Burns
OBJECTIVES: The aim of this study was to characterize the range of management issues raised by adults with cardiovascular sequelae from Kawasaki disease (KD) in childhood. BACKGROUND: Aneurysms resulting from vascular inflammation associated with KD in childhood may remain clinically silent until adulthood. Adults with large aneurysms, unstable angina, or myocardial infarction following KD in childhood present unique challenges to interventional cardiologists and cardiothoracic surgeons...
April 11, 2016: JACC. Cardiovascular Interventions
Ellen S Haddock, Antoanella Calame, Chisato Shimizu, Adriana H Tremoulet, Jane C Burns, Wynnis L Tom
BACKGROUND: A psoriasis-like eruption develops in a subset of patients with Kawasaki disease (KD). OBJECTIVE: We sought to systematically compare KD-associated psoriasiform eruptions with classic psoriasis and the outcomes of KD in children with and without this rash. METHODS: This was a retrospective study of 11 KD cases with a psoriasiform eruption matched 1:2 by age, gender, and ethnicity with psoriasis-only and KD-only controls. Genotyping was performed in 10 cases for a deletion of 2 late cornified envelope (LCE) genes, LCE3C_LCE3B-del, associated with increased risk for pediatric-onset psoriasis...
July 2016: Journal of the American Academy of Dermatology
Zhen Li, Zhou Tan, Shiying Hao, Bo Jin, Xiaohong Deng, Guang Hu, Xiaodan Liu, Jie Zhang, Hua Jin, Min Huang, John T Kanegaye, Adriana H Tremoulet, Jane C Burns, Jianmin Wu, Harvey J Cohen, Xuefeng B Ling
OBJECTIVES: Kawasaki disease (KD) is an acute pediatric vasculitis of infants and young children with unknown etiology and no specific laboratory-based test to identify. A specific molecular diagnostic test is urgently needed to support the clinical decision of proper medical intervention, preventing subsequent complications of coronary artery aneurysms. We used a simple and low-cost colorimetric sensor array to address the lack of a specific diagnostic test to differentiate KD from febrile control (FC) patients with similar rash/fever illnesses...
2016: PloS One
Fujito Numano, Chisato Shimizu, Adriana H Tremoulet, Dan Dyar, Jane C Burns, Beth F Printz
Coronary artery inflammation and aneurysm formation are the most common complications of Kawasaki disease (KD). Valvulitis and myocarditis are also well described and may lead to valvar regurgitation and left ventricular dysfunction. However, functional changes in the right heart have rarely been reported. We noted several acute KD patients with dilated pulmonary arteries (PA) and thus sought to systematically characterize PA size and right-heart function in an unselected cohort of KD patients cared for at a single clinical center...
March 2016: Pediatric Cardiology
Lori B Daniels, Jane C Burns
Acute Kawasaki disease (KD) is diagnosed and treated by pediatricians, but decades later, these individuals are presenting to adult cardiologists with a variety of cardiovascular sequelae, including myocardial ischemia and infarction, congestive heart failure secondary to myocardial fibrosis, and claudication because of vascular insufficiency from thrombosed peripheral arteries. There are no clinical trials to guide management, interventions, and medical therapy in this patient population. This review summarizes the emerging information regarding evaluation of the cardiovascular status of adults decades after childhood KD...
2015: Circulation Journal: Official Journal of the Japanese Circulation Society
Preeti Jaggi, Wei Wang, Igor Dvorchik, Beth Printz, Erika Berry, John P Kovalchin, Karen Texter, Octavio Ramilo, Jane C Burns, Adriana H Tremoulet
BACKGROUND: We sought to determine if fever in the early postintravenous immunoglobulin (IVIG) time period (first 36 hours after IVIG completion) for Kawasaki disease, with or without additional infliximab, can predict IVIG resistance and coronary artery abnormalities (CAA). METHODS: Acute Kawasaki disease subjects enrolled in a clinical trial of infliximab plus IVIG (n = 96) versus placebo/IVIG (n = 94) had temperatures recorded every 6 hours after completion of IVIG infusion...
December 2015: Pediatric Infectious Disease Journal
Fujito Numano, Chisato Shimizu, Susan Jimenez-Fernandez, Matthew Vejar, Toshiaki Oharaseki, Kei Takahashi, Andrea Salgado, Adriana H Tremoulet, John B Gordon, Jane C Burns, Lori B Daniels
BACKGROUNDS: Galectin-3 (Gal-3) is a multifunctional matricellular protein associated with heart failure and cardiovascular events. Gal-3 is required for transforming growth factor-β pathway-mediated myofibroblast activation that is a key process in coronary artery aneurysm formation in Kawasaki Disease (KD). Autopsies from young adults late after KD onset (AKD) have demonstrated bridging fibrosis throughout the myocardium and arteries. In this study, we postulated that Gal-3 may participate in the pathogenesis of myocardial and vascular fibrosis and the remodeling of coronary artery aneurysms following acute KD...
December 15, 2015: International Journal of Cardiology
Adriana H Tremoulet, Janusz Dutkowski, Yuichiro Sato, John T Kanegaye, Xuefeng B Ling, Jane C Burns
BACKGROUND: As Kawasaki disease (KD) shares many clinical features with other more common febrile illnesses and misdiagnosis, leading to a delay in treatment, increases the risk of coronary artery damage, a diagnostic test for KD is urgently needed. We sought to develop a panel of biomarkers that could distinguish between acute KD patients and febrile controls (FC) with sufficient accuracy to be clinically useful. METHODS: Plasma samples were collected from three independent cohorts of FC and acute KD patients who met the American Heart Association definition for KD and presented within the first 10 d of fever...
November 2015: Pediatric Research
S M Dietz, C E Tacke, I M Kuipers, A Wiegman, R J de Winter, J C Burns, J B Gordon, M Groenink, T W Kuijpers
Kawasaki disease (KD) is a paediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. Two guidelines exist regarding the follow-up of patients after KD, by the American Heart Association and the Japanese Circulation Society. After the acute phase, CAA-negative patients are checked for cardiovascular risk assessment or with ECG and echocardiography until 5 years after the disease. In CAA-positive patients, monitoring includes myocardial perfusion imaging, conventional angiography and CT-angiography...
December 2015: Insights Into Imaging
Jane C Burns, Alessandra Franco
The introduction of intravenous immunoglobulin (IVIG) for modulation of inflammation in acute Kawasaki disease was a great therapeutic triumph. However, three decades later, the mechanisms underlying immune regulation by IVIG are only beginning to be revealed. Stimulation of an immature myeloid population of dendritic cells that secretes IL-10 and the elucidation of Fc-specific natural regulatory T cells provide insights into the mechanisms of IVIG. Other potential mechanisms include provision of agent-specific neutralizing antibody, anti-idiotype and anti-cytokine antibodies, blockade of activating Fcγ receptors and stimulation of the inhibitory FcγRIIb receptor...
2015: Expert Review of Clinical Immunology
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