34 results on '"Mark Gorelik"'
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2. Upregulation of type 1 conventional dendritic cells implicates antigen cross-presentation in multisystem inflammatory syndrome
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Robert Winchester, Alexis Boneparth, Mark Gorelik, Samantha B. Gaines, Peter S. Dayan, Mateo L. Amezcua, Janice J. Huang, Tamar R. Lubell, Marissa Dale, and Mark D. Hicar
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Male ,Sialic Acid Binding Ig-like Lectin 1 ,T-Lymphocytes ,medicine.medical_treatment ,CD38 ,Dendritic cells ,Monocytes ,Mean fluorescence intensity, MFI ,Immunology and Allergy ,Child ,Antigens, Viral ,CD64 ,Membrane Glycoproteins ,Multisystem Inflammatory Syndrome in Children, MIS-C ,Dendritic cells, DC ,Systemic Inflammatory Response Syndrome ,Up-Regulation ,Killer Cells, Natural ,Cytokine ,medicine.anatomical_structure ,Child, Preschool ,Cytokines ,Female ,Macrophage activation syndrome, MAS ,Uniform Manifold Approximation and Projection, UMAP ,Adolescent ,CLEC9A ,NK cell cytotoxicity ,Immunology ,Human Leukocyte Antigen, HLA ,Article ,Immunophenotyping ,Interferon-gamma ,Cross-Priming ,medicine ,Humans ,Kawasaki Disease (KD) ,Kawasaki Disease, KD ,Antigen-presenting cell ,CD86 ,Antigen Cross Presentation ,SARS-CoV-2 ,business.industry ,Interleukins ,Monocyte ,Multisystem Inflammatory Syndrome in Children (MIS-C) ,Models, Immunological ,COVID-19 ,HLA-DR Antigens ,Dendritic cell ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Case-Control Studies ,Macrophage activation syndrome ,business - Abstract
Background Multisystem inflammatory syndrome in children (MIS-C) is an acute, febrile, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated syndrome, often with cardiohemodynamic dysfunction. Insight into mechanism of disease is still incomplete. Objective Our objective was to analyze immunologic features of MIS-C patients compared to febrile controls (FC). Methods MIS-C patients were defined by narrow criteria, including having evidence of cardiohemodynamic involvement and no macrophage activation syndrome. Samples were collected from 8 completely treatment-naive patients with MIS-C (SARS-CoV-2 serology positive), 3 patients with unclassified MIS-C–like disease (serology negative), 14 FC, and 5 MIS-C recovery (RCV). Three healthy controls (HCs) were used for comparisons of normal range. Using spectral flow cytometry, we assessed 36 parameters in antigen-presenting cells (APCs) and 29 in T cells. We used biaxial analysis and uniform manifold approximation and projection (UMAP). Results Significant elevations in cytokines including CXCL9, M-CSF, and IL-27 were found in MIS-C compared to FC. Classic monocytes and type 2 dendritic cells (DCs) were downregulated (decreased CD86, HLA-DR) versus HCs; however, type 1 DCs (CD11c+CD141+CLEC9A+) were highly activated in MIS-C patients versus FC, expressing higher levels of CD86, CD275, and atypical conventional DC markers such as CD64, CD115, and CX3CR1. CD169 and CD38 were upregulated in multiple monocyte subtypes. CD56dim/CD57−/KLRGhi/CD161+/CD38− natural killer (NK) cells were a unique subset in MIS-C versus FC without macrophage activation syndrome. Conclusion Orchestrated by complex cytokine signaling, type 1 DC activation and NK dysregulation are key features in the pathophysiology of MIS-C. NK cell findings may suggest a relationship with macrophage activation syndrome, while type 1 DC upregulation implies a role for antigen cross-presentation.
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- 2022
3. A roadmap for the functional annotation of protein families: a community perspective
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Valérie de Crécy-lagard, Rocio Amorin de Hegedus, Cecilia Arighi, Jill Babor, Alex Bateman, Ian Blaby, Crysten Blaby-Haas, Alan J Bridge, Stephen K Burley, Stacey Cleveland, Lucy J Colwell, Ana Conesa, Christian Dallago, Antoine Danchin, Anita de Waard, Adam Deutschbauer, Raquel Dias, Yousong Ding, Gang Fang, Iddo Friedberg, John Gerlt, Joshua Goldford, Mark Gorelik, Benjamin M Gyori, Christopher Henry, Geoffrey Hutinet, Marshall Jaroch, Peter D Karp, Liudmyla Kondratova, Zhiyong Lu, Aron Marchler-Bauer, Maria-Jesus Martin, Claire McWhite, Gaurav D Moghe, Paul Monaghan, Anne Morgat, Christopher J Mungall, Darren A Natale, William C Nelson, Seán O’Donoghue, Christine Orengo, Katherine H O’Toole, Predrag Radivojac, Colbie Reed, Richard J Roberts, Dmitri Rodionov, Irina A Rodionova, Jeffrey D Rudolf, Lana Saleh, Gloria Sheynkman, Francoise Thibaud-Nissen, Paul D Thomas, Peter Uetz, David Vallenet, Erica Watson Carter, Peter R Weigele, Valerie Wood, Elisha M Wood-Charlson, Jin Xu, de Crécy-Lagard, Valérie [0000-0002-9955-3785], Arighi, Cecilia [0000-0002-0803-4817], Bateman, Alex [0000-0002-6982-4660], Blaby, Ian [0000-0002-1631-3154], Bridge, Alan J [0000-0003-2148-9135], Burley, Stephen K [0000-0002-2487-9713], Conesa, Ana [0000-0001-9597-311X], Dallago, Christian [0000-0003-4650-6181], Danchin, Antoine [0000-0002-6350-5001], de Waard, Anita [0000-0002-9034-4119], Ding, Yousong [0000-0001-8610-0659], Friedberg, Iddo [0000-0002-1789-8000], Gyori, Benjamin M [0000-0001-9439-5346], Lu, Zhiyong [0000-0001-9998-916X], Mungall, Christopher J [0000-0002-6601-2165], Radivojac, Predrag [0000-0002-6769-0793], Rodionova, Irina A [0000-0002-6500-2758], Sheynkman, Gloria [0000-0002-4223-9947], Thomas, Paul D [0000-0002-9074-3507], Vallenet, David [0000-0001-6648-0332], Weigele, Peter R [0000-0003-3696-4541], Wood, Valerie [0000-0001-6330-7526], Apollo - University of Cambridge Repository, National Science Foundation (US), National Institutes of Health (US), and National Library of Medicine (US)
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Genome ,Base Sequence ,Human Genome ,Computational Biology ,Proteins ,Molecular Sequence Annotation ,Genomics ,General Biochemistry, Genetics and Molecular Biology ,Data Format ,Library and Information Studies ,Genetics ,Generic health relevance ,General Agricultural and Biological Sciences ,Information Systems - Abstract
Valérie de Crécy-Lagard: et al., Over the last 25 years, biology has entered the genomic era and is becoming a science of 'big data'. Most interpretations of genomic analyses rely on accurate functional annotations of the proteins encoded by more than 500 000 genomes sequenced to date. By different estimates, only half the predicted sequenced proteins carry an accurate functional annotation, and this percentage varies drastically between different organismal lineages. Such a large gap in knowledge hampers all aspects of biological enterprise and, thereby, is standing in the way of genomic biology reaching its full potential. A brainstorming meeting to address this issue funded by the National Science Foundation was held during 3-4 February 2022. Bringing together data scientists, biocurators, computational biologists and experimentalists within the same venue allowed for a comprehensive assessment of the current state of functional annotations of protein families. Further, major issues that were obstructing the field were identified and discussed, which ultimately allowed for the proposal of solutions on how to move forward., National Science Foundation (grant MCB-2129768) to V.d.C.-L; National Institutes of Health Intramural Research Program, National Library of Medicine (Z.L.).
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- 2022
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4. Learning about Kawasaki disease from COVID-19 and the Multisystem Inflammatory Syndrome in Children
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Mark Gorelik
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2019-20 coronavirus outbreak ,Kawasaki disease ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,COVID-19 ,Disease ,Mucocutaneous Lymph Node Syndrome ,medicine.disease ,Multisystem Inflammatory Syndrome in Children ,Systemic Inflammatory Response Syndrome ,toxic shock syndrome ,Immune system ,Pediatrics, Perinatology and Child Health ,Pandemic ,Immunology ,medicine ,Humans ,ALLERGY, IMMUNOLOGY AND RELATED DISORDERS: Edited by Jordan S. Orange ,Severe acute respiratory syndrome coronavirus ,Sibling ,Child ,business - Abstract
Purpose of review Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel syndrome that has appeared in the wake of the severe acute respiratory syndrome coronavirus -2 pandemic, with features that overlap with Kawasaki disease (KD). As a result, new interest and focus have arisen in KD, and specifically mechanisms of the disease. Recent findings A major question in the literature on the nature of MIS-C is if, and how, it may be related to KD. This has been explored using component analysis type studies, as well as other unsupervised analysis, as well as direct comparisons. At present, the answer to this question remains opaque, and several studies have interpreted their findings in opposing ways. Studies seem to suggest some relationship, but that MIS-C and KD are not the same syndrome. Summary Study of MIS-C strengthens the likelihood that KD is a postinfectious immune response, and that perhaps multiple infectious agents or viruses underlie the disease. MIS-C and KD, while not the same disease, could plausibly be sibling disorders that fall under a larger syndrome of postacute autoimmune febrile responses to infection, along with Kawasaki shock syndrome.
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- 2021
5. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
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Yih Chang Lin, Maria Ibarra, Robert P. Sundel, Amy S. Turner, Ann Warner, Carol A. Langford, Andy Abril, Gordon H. Guyatt, Doyt L. Conn, Amy M. Archer, John H. Stone, Nedaa Husainat, Kathy A. Full, Reem A. Mustafa, Kevin Byram, Jason M. Springer, Rennie L. Rhee, Anisha B. Dua, Mohamad A. Kalot, Peter A. Merkel, Marat Turgunbaev, Sangeeta Sule, Mehrdad Maz, Susan Kim, Sharon A. Chung, Mark Gorelik, Peter C. Grayson, Omar I. Vitobaldi, Philip Seo, Alexandra Villa-Forte, Lisa Imundo, and Karen E. James
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medicine.medical_specialty ,Consensus ,Clinical Decision-Making ,Immunology ,Population ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Severity of Illness Index ,Antibodies, Antineutrophil Cytoplasmic ,Decision Support Techniques ,Rheumatology ,Maintenance therapy ,medicine ,Humans ,Immunology and Allergy ,Intensive care medicine ,education ,Anti-neutrophil cytoplasmic antibody ,education.field_of_study ,Evidence-Based Medicine ,business.industry ,Guideline ,medicine.disease ,Treatment Outcome ,Adjunctive treatment ,Microscopic polyangiitis ,business ,Granulomatosis with polyangiitis ,Mepolizumab ,Biomarkers ,Immunosuppressive Agents ,medicine.drug - Abstract
Objective To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. Conclusion This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.
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- 2021
6. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis
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Yih Chang Lin, Kevin Byram, Peter C. Grayson, Kathy A. Full, Jason M. Springer, Sharon A. Chung, Robert P. Sundel, Marat Turgunbaev, Maria Ibarra, Sangeeta Sule, Rennie L. Rhee, Amy S. Turner, Mark Gorelik, Mohamad A. Kalot, Peter A. Merkel, Carol A. Langford, Nedaa Husainat, Mehrdad Maz, Ann Warner, Amy M. Archer, Andy Abril, Doyt L. Conn, Karen E. James, Reem A. Mustafa, Anisha B. Dua, Philip Seo, Alexandra Villa-Forte, Gordon H. Guyatt, John H. Stone, Susan Kim, Lisa Imundo, and Omar I. Vitobaldi
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medicine.medical_specialty ,Consensus ,Clinical Decision-Making ,Giant Cell Arteritis ,Immunology ,Population ,MEDLINE ,Decision Support Techniques ,Rheumatology ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,Disease management (health) ,skin and connective tissue diseases ,Intensive care medicine ,education ,Grading (education) ,Glucocorticoids ,education.field_of_study ,Evidence-Based Medicine ,business.industry ,Disease Management ,Guideline ,medicine.disease ,Takayasu Arteritis ,United States ,Giant cell arteritis ,Treatment Outcome ,Drug Therapy, Combination ,business ,Vasculitis ,Immunosuppressive Agents - Abstract
Objective To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. Conclusion These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.
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- 2021
7. Reversible Coronary Artery Aneurysm With Delayed Anti-inflammatory Therapy in Multisystem Inflammatory Syndrome in Children
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Mark Gorelik, Sanghee Suh, Patrick T. Wilson, Ramzi Shaykh, Shoshana Leftin, Robert Spencer, and Rebekah Diamond
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0301 basic medicine ,Tachycardia ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,coronary vessel anomaly ,medicine.drug_class ,Hemodynamics ,Case Report ,Disease ,030105 genetics & heredity ,hemodynamics ,tachycardia ,Anti-inflammatory ,LAD, left anterior descending ,03 medical and health sciences ,0302 clinical medicine ,Clinical Case ,shortness of breath ,Internal medicine ,Medicine ,echocardiography ,Diseases of the circulatory (Cardiovascular) system ,Coronary artery aneurysm ,business.industry ,SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2 ,autoimmune ,Delayed treatment ,KD, Kawasaki disease ,medicine.disease ,Natural history ,HD, hospital day ,RC666-701 ,Cardiology ,NT-proBNP, N-terminal pro–B-type natriuretic peptide ,MIS-C, multisystem inflammatory syndrome in children ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
A 4-year-old boy with multisystem inflammatory syndrome in children before widespread recognition of this disease developed complications, including coronary artery aneurysm, without anti-inflammatory treatment. With delayed treatment, all sequelae resolved. This case demonstrates a natural history supporting the role of anti-inflammatory treatment even with delayed or equivocal diagnosis. (Level of Difficulty: Intermediate.), Graphical abstract
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- 2021
8. The potential role of Colchicine in preventing coronary vascular disease in childhood‐onset lupus: a new view on an old drug
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Mark Gorelik, Stacy P. Ardoin, and Dori Abel
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medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Review ,Coronary Artery Disease ,Disease ,030204 cardiovascular system & hematology ,Protective Agents ,Systemic lupus erythematous ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Cardiovascular Disease ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Colchicine ,Myocardial infarction ,Age of Onset ,Child ,Cause of death ,030203 arthritis & rheumatology ,Systemic lupus erythematosus ,Vascular disease ,business.industry ,Prevention ,lcsh:RJ1-570 ,lcsh:Pediatrics ,medicine.disease ,Atherosclerosis ,chemistry ,Heart Disease Risk Factors ,Pediatrics, Perinatology and Child Health ,lcsh:RC925-935 ,business - Abstract
Background Patients with systemic lupus erythematous have a significantly increased risk of cardiovascular disease, which is not fully explained by traditional cardiovascular disease risk factors. Despite increasing life expectancy in patients with systemic lupus erythematous, mortality due to cardiovascular disease, the major cause of death in these patients, has not changed. Children with lupus suffer from more aggressive disease compared to their adult counterparts, and there is a growing concern for their increased risk of cardiovascular disease as they age. Body: There is an unmet need for therapies to address the increased risk of cardiovascular disease in childhood-onset lupus. Colchicine has many anti-inflammatory and cardiovascular protective properties, including inhibition of IL-1β and IL-18 activity, key proinflammatory cytokines that are predictive of future adverse cardiovascular events. In the Colchicine Cardiovascular Outcomes Trial (COLCOT), colchicine was recently found to have significant benefit with minimal risk in adults with previous myocardial infarction for prevention of secondary vascular disease. While adult studies are promising, no studies have been conducted in pediatric patients to investigate colchicine’s potential for cardiovascular protection in children and adolescents with lupus. Conclusions Studies investigating colchicine’s potential role for cardiovascular protection are needed in pediatric patients with systemic lupus erythematous.
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- 2021
9. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3
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Lauren A. Henderson, Scott W. Canna, Kevin G. Friedman, Mark Gorelik, Sivia K. Lapidus, Hamid Bassiri, Edward M. Behrens, Kate F. Kernan, Grant S. Schulert, Philip Seo, Mary Beth F. Son, Adriana H. Tremoulet, Christina VanderPluym, Rae S. M. Yeung, Amy S. Mudano, Amy S. Turner, David R. Karp, and Jay J. Mehta
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Adult ,Rheumatology ,SARS-CoV-2 ,Immunology ,COVID-19 ,Humans ,Immunology and Allergy ,Child ,Systemic Inflammatory Response Syndrome ,United States - Abstract
To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of SARS-CoV-2 infection. Recommendations are also provided for children with hyperinflammation during COVID-19, the acute, infectious phase of SARS-CoV-2 infection.The Task Force is composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting.The guidance was approved in June 2020 and updated in November 2020 and October 2021, and consists of 41 final guidance statements accompanied by flow diagrams depicting the diagnostic pathway for MIS-C and recommendations for initial immunomodulatory treatment of MIS-C.Our understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.
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- 2022
10. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 1
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Mark Gorelik, Anne Ferris, Grant S. Schulert, Philip Seo, Rae S. M. Yeung, Mary Beth F. Son, Amy S. Mudano, Kate F. Kernan, Adriana H. Tremoulet, Edward M. Behrens, Sivia K. Lapidus, Jay J. Mehta, Scott W. Canna, David R. Karp, Hamid Bassiri, Kevin G. Friedman, Amy S. Turner, and Lauren A. Henderson
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medicine.medical_specialty ,Consensus ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,MEDLINE ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,030225 pediatrics ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Intensive care medicine ,book ,business.industry ,COVID-19 ,Systemic Inflammatory Response Syndrome ,Living document ,Pediatric Infectious Disease ,Etiology ,book.journal ,business ,Pediatric population - Abstract
OBJECTIVE: To provide guidance on the management of multisystem inflammatory syndrome in children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to provide recommendations for children with hyperinflammation during coronavirus disease 2019 (COVID-19), the acute, infectious phase of SARS-CoV-2 infection. METHODS: A multidisciplinary task force was convened by the American College of Rheumatology (ACR) to provide guidance on the management of MIS-C associated with SARS-CoV-2 and hyperinflammation in COVID-19. The task force was composed of 9 pediatric rheumatologists, 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved 2 rounds of anonymous voting and 2 webinars. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate), and consensus was rated as low, moderate, or high based on dispersion of the votes along the numeric scale. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, as prespecified prior to voting. RESULTS: The ACR task force approved a total of 128 guidance statements addressing the management of MIS-C and hyperinflammation in pediatric COVID-19. These statements were refined into 40 final clinical guidance statements, accompanied by a flow diagram depicting the diagnostic pathway for MIS-C. CONCLUSION: Our understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. The guidance provided in this "living document" reflects currently available evidence, coupled with expert opinion, and will be revised as further evidence becomes available.
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- 2020
11. Ventricular Function and Tissue Characterization By Cardiac MRI in Children Following Hospitalization for Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Study
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Michael P Dilorenzo, Kanwal M Farooqi, Amee M Shah, Alexandra Channing, Jamie K Harrington, Thomas J Connors, Karen Martirosyan, Usha S Krishnan, Anne Ferris, Rachel J. Weller, Donna L Farber, Joshua D. Milner, Mark Gorelik, Erika B Rosenzweig, and Brett R Anderson
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cardiovascular system ,cardiovascular diseases ,Article - Abstract
Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe life-threatening manifestation of SARS-CoV-2 infection. Acute cardiac dysfunction and resultant cardiogenic shock are common in children with MIS-C. While most children recover rapidly from acute illness, the long-term impact on the myocardium and cardiac function is unknown. Methods In this prospective study, cardiac MRI (CMR) was performed on patients 10 years old. Native T1 and T2 mapping values were compared with 20 children with normal CMR examinations. Results We performed CMRs on 13 subjects at a median age of 13.6 years (interquartile range [IQR] 11.9-16.0) and a median time from hospitalization of 8.2 months (IQR 6.8-9.6). Twelve subjects displayed normal ventricular function with a median left ventricle ejection fraction (LVEF) of 57.2% (IQR 56.1-58.4) and median right ventricular (RV) EF of 53.1% (IQR 52.0-55.7). One subject had low normal EF (52%). There was normal T2 and native T1 as compared to normal controls. There was qualitatively no evidence of edema by T2 weighted imaging. One subject had late gadolinium enhancement (LGE) at the inferior insertion point and mid-ventricular inferolateral region, with normal EF, no evidence of edema or perfusion defects, and normal T1 and T2 times. When stratifying by a history of abnormal LVEF (LVEF
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- 2022
12. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease
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Mark Gorelik, Sharon A. Chung, Kaveh Ardalan, Bryce A. Binstadt, Kevin Friedman, Kristen Hayward, Lisa F. Imundo, Sivia K. Lapidus, Susan Kim, Mary Beth Son, Sangeeta Sule, Adriana H. Tremoulet, Heather Van Mater, Cagri Yildirim‐Toruner, Carol A. Langford, Mehrdad Maz, Andy Abril, Gordon Guyatt, Amy M. Archer, Doyt L. Conn, Kathy A. Full, Peter C. Grayson, Maria F. Ibarra, Peter A. Merkel, Rennie L. Rhee, Philip Seo, John H. Stone, Robert P. Sundel, Omar I. Vitobaldi, Ann Warner, Kevin Byram, Anisha B. Dua, Nedaa Husainat, Karen E. James, Mohamad Kalot, Yih Chang Lin, Jason M. Springer, Marat Turgunbaev, Alexandra Villa‐Forte, Amy S. Turner, and Reem A. Mustafa
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Evidence-Based Medicine ,Rheumatology ,Immunology ,Immunology and Allergy ,Humans ,Immunoglobulins, Intravenous ,Mucocutaneous Lymph Node Syndrome ,Immunosuppressive Agents ,United States - Abstract
To provide evidence-based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists.Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) question format. Systematic literature reviews were conducted for each PICO question. We used the Grading of Recommendations, Assessment, Development and Evaluation method to assess the quality of evidence and formulate recommendations. Each recommendation required consensus from at least 70% of the Voting Panel.We present 1 good practice statement, 11 recommendations, and 1 ungraded position statement to guide the management of KD and clinical scenarios of suspected KD. These recommendations for KD are focused on situations in which input from rheumatologists may be requested by other managing specialists, such as in cases of treatment-refractory, severe, or complicated KD. The good practice statement affirms that all patients with KD should receive initial treatment with intravenous immunoglobulin (IVIG). In addition, we developed 7 strong and 4 conditional recommendations for the management of KD or suspected KD. Strong recommendations include prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in the setting of unexplained macrophage activation syndrome or shock. Conditional recommendations include use of IVIG with other adjuvant agents for patients with KD and high-risk features of IVIG resistance and/or coronary artery aneurysms. These recommendations endorse minimizing risk to the patient by using established therapy promptly at disease onset and identifying situations in which adjunctive therapy may be warranted.These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and use of echocardiography in patients with suspected or confirmed KD.
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- 2021
13. Longitudinal Outcomes for Multisystem Inflammatory Syndrome in Children
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Kanwal M. Farooqi, Brett R. Anderson, Erika B. Rosenzweig, Amee Shah, Usha Krishnan, Junhui Mi, Pengfei Jiang, Michael P. DiLorenzo, Elizabeth Abrahams, Angela Chan, Nikhil Pasumarti, Anne Ferris, Philip Zachariah, Mark Gorelik, Sanghee Suh, Rachel Weller, and Joshua D. Milner
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Male ,Chemokine ,medicine.medical_specialty ,Critical Care ,New York ,Aftercare ,Inflammation ,Gastroenterology ,Interquartile range ,Intensive care ,Internal medicine ,medicine ,Humans ,Child ,Pandemics ,Retrospective Studies ,biology ,business.industry ,COVID-19 ,Infant ,Interleukin ,Retrospective cohort study ,medicine.disease ,Patient Discharge ,Systemic Inflammatory Response Syndrome ,Systemic inflammatory response syndrome ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,biology.protein ,Female ,medicine.symptom ,business ,Follow-Up Studies - Abstract
BACKGROUND In spring 2020, a novel hyperinflammatory process associated with severe acute respiratory syndrome coronavirus 2 multisystem inflammatory syndrome in children (MIS-C) was described. The long-term impact remains unknown. We report longitudinal outcomes from a New York interdisciplinary follow-up program. METHODS All children RESULTS In total, 45 children were admitted with MIS-C. The median time to last follow-up was 5.8 months (interquartile range 1.3–6.7). Of those admitted, 76% required intensive care and 64% required vasopressors and/or inotropes. On admission, patients exhibited significant nonspecific inflammation, generalized lymphopenia, and thrombocytopenia. Soluble interleukin (IL) IL-2R, IL-6, IL-10, IL-17, IL-18, and C-X-C Motif Chemokine Ligand 9 were elevated. A total of 80% (n = 36) had at least mild and 44% (n = 20) had moderate-severe echocardiographic abnormalities including coronary abnormalities (9% had a z score of 2–2.5; 7% had a z score > 2.5). Whereas most inflammatory markers normalized by 1 to 4 weeks, 32% (n = 11 of 34) exhibited persistent lymphocytosis, with increased double-negative T cells in 96% of assessed patients (n = 23 of 24). By 1 to 4 weeks, only 18% (n = 7 of 39) had mild echocardiographic findings; all had normal coronaries. At 1 to 4 months, the proportion of double-negative T cells remained elevated in 92% (median 9%). At 4 to 9 months, only 1 child had persistent mild dysfunction. One had mild mitral and/or tricuspid regurgitation. CONCLUSIONS Although the majority of children with MIS-C present critically ill, most inflammatory and cardiac manifestations in our cohort resolved rapidly.
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- 2021
14. A dermatologic perspective on multisystem inflammatory syndrome in children
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Fludiona Naka, Laura Melnick, Mark Gorelik, and Kimberly D. Morel
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medicine.medical_specialty ,Abdominal pain ,mucocutaneous manifestations ,endocrine system diseases ,Adolescent ,Mucocutaneous zone ,coronavirus ,MIS-C ,rash ,Dermatology ,Mucocutaneous Lymph Node Syndrome ,Skin Diseases ,Article ,Diagnosis, Differential ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Conjunctivitis, Viral ,0302 clinical medicine ,children ,COVID-19: Important Updates and Developments Edited by Franco Rongioletti, MD and Leonard Hoenig, MD ,medicine ,otorhinolaryngologic diseases ,Humans ,Child ,Neck stiffness ,030203 arthritis & rheumatology ,Respiratory distress ,business.industry ,SARS-CoV-2 ,Organ dysfunction ,Infant, Newborn ,Mouth Mucosa ,Infant ,COVID-19 ,medicine.disease ,Systemic Inflammatory Response Syndrome ,Systemic inflammatory response syndrome ,Child, Preschool ,Differential diagnosis ,medicine.symptom ,business ,Mouth Diseases - Abstract
Highlights • Mucocutaneous manifestations of MIS-C: conjunctivitis, oral mucosal changes, rash. • The rash of MIS-C is typically diffuse and non-specific. • Mucocutaneous manifestations of MIS-C are more common in younger children. • KD and MIS-C differ in mean age of onset, race predilection, and associated symptoms., As of May 2020, an emerging immune-mediated syndrome primarily affecting children has been detected primarily in Europe and the United States. The incidence of this syndrome appears to mirror the initial infectious assault with a delay of several weeks. This syndrome has been termed multisystem inflammatory syndrome in children (MIS-C), and is observed in association with the coronavirus disease 2019 (COVID-19). The phenotypes of presentation include several characteristic features, including prolonged fever, skin eruptions, neck stiffness, and gastrointestinal manifestations with pronounced abdominal pain. Shock and organ dysfunction on presentation are frequent but inconsistent, while respiratory distress is typically, and notably, absent. We have reviewed the recent published data aiming to better understanding MIS-C, with a focus on its mucocutaneous manifestations.
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- 2021
15. Therapeutic approaches to pediatric COVID-19: an online survey of pediatric rheumatologists
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Ales Janda, Maximilian Heeg, Mark Gorelik, Christian M. Hedrich, Scott W. Canna, Catharina Schuetz, Claas Hinze, Klaus-Michael Debatin, Kirsten Minden, Fabian Speth, and Ansgar Schulz
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medicine.medical_specialty ,Cyclophosphamide ,Immunology ,Observational Research ,Azithromycin ,Antiviral Agents ,Autoimmune Diseases ,Immunomodulation ,chemistry.chemical_compound ,Tocilizumab ,Opinion poll ,Rheumatology ,Internal medicine ,Surveys and Questionnaires ,Autoimmune disease ,Immunology and Allergy ,Medicine ,Humans ,Pediatric rheumatology ,Stage (cooking) ,Child ,Children ,Pandemics ,Inflammation ,Anakinra ,business.industry ,SARS-CoV-2 ,COVID-19 ,Hydroxychloroquine ,COVID-19 Drug Treatment ,Treatment ,Canakinumab ,chemistry ,Antirheumatic Agents ,Case-Control Studies ,business ,medicine.drug - Abstract
Data on therapy of COVID-19 in immunocompetent and immunosuppressed children are scarce. We aimed to explore management strategies of pediatric rheumatologists. All subscribers to international Pediatric Rheumatology Bulletin Board were invited to take part in an online survey on therapeutic approaches to COVID-19 in healthy children and children with autoimmune/inflammatory diseases (AID). Off-label therapies would be considered by 90.3% of the 93 participating respondents. In stable patients with COVID-19 on oxygen supply (stage I), use of remdesivir (48.3%), azithromycin (26.6%), oral corticosteroids (25.4%) and/or hydroxychloroquine (21.9%) would be recommended. In case of early signs of “cytokine storm” (stage II) or in critically ill patients (stage III) (a) anakinra (79.5% stage II; 83.6% stage III) or tocilizumab (58.0% and 87.0%, respectively); (b) corticosteroids (oral 67.2% stage II, intravenously 81.7% stage III); (c) intravenous immunoglobulins (both stages 56.5%); or (d) remdesivir (both stages 46.7%) were considered. In AID, > 94.2% of the respondents would not support a preventive adaptation of the immunomodulating therapy. In case of mild COVID-19, more than 50% of the respondents would continue pre-existing treatment with immunoglobulins (100%), hydroxychloroquine (94.2%), anakinra (79.2%) or canakinumab (72.5%), or tocilizumab (69.8%). Long-term corticosteroids would be reduced by 26.9% ( 2 mg/kg/day), respectively, with only 5.8% of respondents voting to discontinue the therapy. Conversely, more than 75% of respondents would refrain from administering cyclophosphamide and anti-CD20-antibodies. As evidence on management of pediatric COVID-19 is incomplete, continuous and critical expert opinion and knowledge exchange is helpful. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04824-4.
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- 2021
16. The Intriguing Role of Thalamic Structure and Function in Youth With and at Familial Risk for Bipolar Disorder
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Manpreet Singh, Aaron Gorelik, Mark Gorelik, Kiki Chang, Ian Gotlib, Allan Reiss, and Akua Nimarko
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Biological Psychiatry - Published
- 2022
17. Inhibition of IL-6 in the LCWE Mouse Model of Kawasaki Disease Inhibits Acute Phase Reactant Serum Amyloid A but Fails to Attenuate Vasculitis
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Rebecca A. Porritt, Carol Chase Huizar, Edward J. Dick, Shyamesh Kumar, Renee Escalona, Angela C. Gomez, Stefani Marek-Iannucci, Magali Noval Rivas, Jean Patterson, Thomas G. Forsthuber, Moshe Arditi, and Mark Gorelik
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Male ,Proteomics ,0301 basic medicine ,Heart disease ,030204 cardiovascular system & hematology ,Pharmacology ,vasculitis ,STAT3 ,Mice ,0302 clinical medicine ,Cell Wall ,magnetic and microwave proteomics ,Immunology and Allergy ,Original Research ,biology ,medicine.diagnostic_test ,Acute-phase protein ,Lacticaseibacillus casei ,medicine.symptom ,anakinra ,medicine.drug ,STAT3 Transcription Factor ,lcsh:Immunologic diseases. Allergy ,Immunology ,Inflammation ,Mucocutaneous Lymph Node Syndrome ,03 medical and health sciences ,Western blot ,medicine ,Animals ,Serum amyloid A ,Interleukin 6 ,Serum Amyloid A Protein ,IL-6 ,Anakinra ,Kawasaki disease ,IL-1 ,Interleukin-6 ,business.industry ,Myocardium ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Interleukin 1 Receptor Antagonist Protein ,030104 developmental biology ,biology.protein ,LCWE ,lcsh:RC581-607 ,business - Abstract
ObjectiveKawasaki disease (KD) is the most common cause of acquired pediatric heart disease in the developed world. 10% of KD patients are resistant to front-line therapy, and no interventions exist to address secondary complications such as myocardial fibrosis. We sought to identify proteins and pathways associated with disease and anti-IL-1 treatment in a mouse model of KD.MethodsVasculitis was induced via Lactobacillus casei cell wall extract (LCWE) injection in 5-week-old male mice. Groups of mice were injected with LCWE alone, LCWE and IL-1 receptor antagonist anakinra, or saline for controls. Upper heart tissue was assessed by quantitative mass spectrometry analysis. Expression and activation of STAT3 was assessed by immunohistochemistry, immunofluorescence and Western blot, and IL-6 expression by RNA-seq and ELISA. A STAT3 small molecular inhibitor and anti-IL-6R antibody were used to evaluate the role of STAT3 and IL-6 in disease development.ResultsSTAT3 was highly expressed and phosphorylated in cardiac tissue of LCWE-injected mice, and reduced following anakinra treatment. Il6 and Stat3 gene expression was enhanced in abdominal aorta of LCWE-injected mice and reduced with Anakinra treatment. IL-6 serum levels were enhanced in LCWE-injected mice and normalized by anakinra. However, neither inhibition of STAT3 nor blockade of IL-6 altered disease development.ConclusionProteomic analysis of cardiac tissues demonstrates differential protein expression between KD-like, control and anakinra treated cardiac tissue. STAT3 and IL-6 were highly upregulated with LCWE and normalized by anakinra treatment. However, both STAT3 and IL-6 were dispensable for disease development indicating they may be bystanders of inflammation.
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- 2021
18. Reply
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Adriana H. Tremoulet, Rae S. M. Yeung, Scott W. Canna, Kevin G. Friedman, Grant S. Schulert, Kate F. Kernan, Mary Beth F. Son, Lauren A. Henderson, Philip Seo, Sivia K. Lapidus, Mark Gorelik, Jay J. Mehta, Edward M. Behrens, Hamid Bassiri, Anne Ferris, and David R. Karp
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medicine.medical_specialty ,education.field_of_study ,Ejection fraction ,business.industry ,Task force ,Immunology ,Population ,030204 cardiovascular system & hematology ,medicine.disease ,Thrombosis ,Rheumatology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Internal medicine ,medicine ,Immunology and Allergy ,In patient ,030212 general & internal medicine ,Treatment decision making ,business ,education ,Artery - Abstract
We thank Dr. Kotnik and colleagues for their commentary on the American College of Rheumatology's clinical guidance for pediatric patients with multisystem inflammatory syndrome in children (MIS-C). The use of anticoagulation in this population remains an intensely debated topic with little clinical evidence to guide treatment decisions. For this reason, the task force was only able to achieve consensus on recommending anticoagulation in patients with larger coronary artery aneurysms (CAAs) (z-score >10) and significant cardiac dysfunction (ejection fraction < 35%) based on the well-established risk for thrombosis in patients with these clinical features.(1, 2).
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- 2021
19. Multisystem Inflammatory Syndrome in Children Associated With Coronavirus Disease 2019 in a Children’s Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up
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Juan Duran, Steven G. Kernie, Maria Zorrilla, Wendy G Silver, Alexis Boneparth, Maria C. Garzon, Brian Jonat, Philip Zachariah, Jennifer Cheng, Leanne Svoboda, Amee Shah, Eva W. Cheung, Candace Johnson, Kara Gross Margolis, Larisa Broglie, Kimberly D. Morel, Cindy E. Neunert, Andrew S Geneslaw, Mark Gorelik, Irene D. Lytrivi, and Joshua D. Milner
- Subjects
Pediatrics ,medicine.medical_specialty ,pediatrics ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Patient characteristics ,Disease ,Critical Care and Intensive Care Medicine ,coronavirus disease 2019 ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Pandemic ,Humans ,Medicine ,clinical protocols ,Pediatrics, Perinatology, and Child Health ,Child ,pediatric multisystem inflammatory disease ,SARS-CoV-2 ,business.industry ,Online Clinical Investigations ,COVID-19 ,030208 emergency & critical care medicine ,Syndrome ,medicine.disease ,coronavirus disease 2019 related ,Disease control ,Systemic Inflammatory Response Syndrome ,critical care ,Systemic inflammatory response syndrome ,Pediatrics, Perinatology and Child Health ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,New York City ,business ,severe acute respiratory syndrome coronavirus 2 ,Follow-Up Studies - Abstract
Supplemental Digital Content is available in the text., Objectives: The disease caused by severe acute respiratory syndrome coronavirus 2, known as coronavirus disease 2019, has resulted in a global pandemic. Reports are emerging of a new severe hyperinflammatory syndrome related to coronavirus disease 2019 in children and adolescents. The Centers for Disease Control and Prevention has designated this disease multisystem inflammatory syndrome in children. Our objective was to develop a clinical inpatient protocol for the evaluation, management, and follow-up of patients with this syndrome. Data Sources: The protocol was developed by a multidisciplinary team based on relevant literature related to coronavirus disease 2019, multisystem inflammatory syndrome in children, and related inflammatory syndromes, as well as our experience caring for children with multisystem inflammatory syndrome in children. Data were obtained on patients with multisystem inflammatory syndrome in children at our institution from the pre-protocol and post-protocol periods. Data Synthesis: Our protocol was developed in order to identify cases of multisystem inflammatory syndrome in children with high sensitivity, stratify risk to guide treatment, recognize co-infectious or co-inflammatory processes, mitigate coronary artery abnormalities, and manage hyperinflammatory shock. Key elements of evaluation include case identification using broad clinical characteristics and comprehensive laboratory and imaging investigations. Treatment centers around glucocorticoids and IV immunoglobulin with biologic immunomodulators as adjuncts. Multidisciplinary follow-up after discharge is indicated to manage continued outpatient therapy and evaluate for disease sequelae. In nearly 2 months, we admitted 54 patients with multisystem inflammatory syndrome in children, all of whom survived without the need for invasive ventilatory or mechanical circulatory support. After institution of this protocol, patients received earlier treatment and had shorter lengths of hospital stay. Conclusions: This report provides guidance to clinicians on evaluation, management, and follow-up of patients with a novel hyperinflammatory syndrome related to coronavirus disease 2019 known as multisystem inflammatory syndrome in children. It is based on the relevant literature and our experience. Instituting such a protocol during a global pandemic is feasible and is associated with patients receiving treatment and returning home more quickly.
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- 2020
- Full Text
- View/download PDF
20. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa
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Yih Chang Lin, Marat Turgunbaev, Kevin Byram, Nedaa Husainat, Sangeeta Sule, Mehrdad Maz, Philip Seo, Alexandra Villa-Forte, Sharon A. Chung, Karen E. James, Robert P. Sundel, Amy S. Turner, Amy M. Archer, John H. Stone, Susan Kim, Doyt L. Conn, Ann Warner, Anisha B. Dua, Maria Ibarra, Mohamad A. Kalot, Peter A. Merkel, Kathy A. Full, Peter C. Grayson, Mark Gorelik, Rennie L. Rhee, Gordon H. Guyatt, Jason M. Springer, Omar I. Vitobaldi, Lisa Imundo, Reem A. Mustafa, Carol A. Langford, and Andy Abril
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medicine.medical_specialty ,Consensus ,Immunology ,Population ,Clinical Decision-Making ,MEDLINE ,Disease ,Severity of Illness Index ,Decision Support Techniques ,Rheumatology ,medicine ,Immunology and Allergy ,Humans ,Disease management (health) ,Intensive care medicine ,education ,Cyclophosphamide ,Glucocorticoids ,education.field_of_study ,Evidence-Based Medicine ,Polyarteritis nodosa ,business.industry ,Disease Management ,Foundation (evidence) ,Guideline ,medicine.disease ,United States ,Polyarteritis Nodosa ,Treatment Outcome ,Antirheumatic Agents ,Drug Therapy, Combination ,business ,Vasculitis ,Immunosuppressive Agents - Abstract
Objective To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Methods Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. Conclusion These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.
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- 2020
21. COVID-19 Inflammatory Syndrome With Clinical Features Resembling Kawasaki Disease
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Rebecca F. Hough, Karen P. Acker, Robert Spencer, Alexis Boneparth, Mark Gorelik, Usha Krishnan, and Ryan C. Closson
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Male ,Pathology ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Disease ,Mucocutaneous Lymph Node Syndrome ,medicine.disease_cause ,Risk Assessment ,Sampling Studies ,Diagnosis, Differential ,Desquamation ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,medicine ,Humans ,Pandemics ,Coronavirus ,biology ,business.industry ,COVID-19 ,Immunoglobulins, Intravenous ,medicine.disease ,Combined Modality Therapy ,Rash ,Systemic Inflammatory Response Syndrome ,Pneumonia ,Treatment Outcome ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,biology.protein ,Female ,Kawasaki disease ,Antibody ,medicine.symptom ,Coronavirus Infections ,business - Abstract
We describe 2 patients with coronavirus disease who had multiple clinical features suggestive of Kawasaki disease (KD). Both patients presented with fever lasting >5 days and were found to have rash, conjunctival injection, and swollen lips. One patient also had extremity swelling, whereas the other developed desquamation of the fingers. In both cases, laboratory results were similar to those seen in KD. These patients had highly unusual but similar features, and both appeared to respond favorably to treatment. It remains unclear whether these patients had true KD or manifestations of coronavirus disease that resembled KD.
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- 2020
22. Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City
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Steven G. Kernie, Joshua D. Milner, Eva W. Cheung, Philip Zachariah, Mark Gorelik, Jordan S. Orange, and Alexis Boneparth
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2019-20 coronavirus outbreak ,Pediatrics ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,010102 general mathematics ,Toxic shock syndrome ,General Medicine ,medicine.disease ,01 natural sciences ,City hospital ,Systemic inflammatory response syndrome ,03 medical and health sciences ,Pneumonia ,0302 clinical medicine ,Research Letter ,medicine ,Kawasaki disease ,030212 general & internal medicine ,0101 mathematics ,skin and connective tissue diseases ,business ,Coronavirus Infections - Abstract
This case series describes clinical characteristics, treatment, and outcomes of 17 previously healthy SARS-CoV-2-infected children and adolescents with an inflammatory phenotype overlapping with but distinct from Kawasaki disease and toxic shock syndrome admitted to a New York City hospital in late April and early May 2020.
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- 2020
- Full Text
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23. Complete Regression of Giant Aneurysms in an Infant with Delayed Diagnosis and Refractory Kawasaki Disease via Combination Anticytokine Therapy: Case Report and Review of Similar Cases
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Maegan Williams, Lakshmi Nagaraju, and Mark Gorelik
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Pediatrics ,medicine.medical_specialty ,Heart disease ,business.industry ,Case Report ,General Medicine ,Disease ,Diseases of the musculoskeletal system ,medicine.disease ,Delayed diagnosis ,Anticytokine Therapy ,Refractory ,RC925-935 ,medicine ,Kawasaki disease ,Vasculitis ,Prospective cohort study ,business - Abstract
Background. Kawasaki disease (KD) is an inflammatory vasculitis and is the most common cause of acquired childhood heart disease in developed countries. Current treatment with intravenous immunoglobulin (IVIG) is often ineffective in patients with delayed or refractory disease. We present a case of combination anticytokine therapy in an infant with delayed and refractory KD. Case Presentation. A 3-month-old infant presented with refractory KD with giant aneurysms after a delayed diagnosis of one month. Use of combination anticytokine therapy led to resolution of giant aneurysms over approximately 6 months. Conclusions. Our case is unique in effective use of anticytokine therapy in very delayed disease with giant aneurysms. Additionally, we review other cases for a broader perspective. Prospective study of anticytokine therapy for patients with giant aneurysms may be warranted.
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- 2020
24. Discriminating Multisystem Inflammatory Syndrome in Children Requiring Treatment from Common Febrile Conditions in Outpatient Settings
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Zachary Pitkowsky, Taylor B. Sewell, Rebecca F. Carlin, Josh D. Milner, Eva W. Cheung, Mark Gorelik, Alexis Boneparth, Philip Zachariah, Brett R. Anderson, Melissa S. Stockwell, Steve Caddle, Erika Grun Landau, Laura Robbins-Milne, Avital M. Fischer, and Dori Abel
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Male ,Multisystem Inflammatory Syndrome in Children, (MIS-C) ,medicine.medical_specialty ,Abdominal pain ,Adolescent ,Fever ,Objective data ,medicine.disease_cause ,Logistic regression ,Multisystem Inflammatory Syndrome in Children ,Intravenous immunoglobulin, (IVIG) ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,N-Terminal Brain Natriuretic Peptide, (ntBNP) ,030225 pediatrics ,Internal medicine ,Acute care ,Ambulatory Care ,medicine ,Humans ,Outpatient clinic ,Pediatrics, Perinatology, and Child Health ,030212 general & internal medicine ,Child ,Emergency Department, (ED) ,Retrospective Studies ,Neck pain ,Kawasaki disease ,SARS-CoV-2 ,business.industry ,Age Factors ,COVID-19 ,Original Articles ,Rash ,Systemic Inflammatory Response Syndrome ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Symptom Assessment ,myocarditis ,Irritation ,medicine.symptom ,business - Abstract
OBJECTIVES: To examine whether patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated well-defined clinical features distinct from other febrile outpatients, given the difficulties of seeing acute care visits during the severe acute respiratory syndrome coronavirus 2 pandemic and the risks associated with both over- and underdiagnosis of MIS-C. STUDY DESIGN: This case-controlled study compared patients diagnosed with and treated for MIS-C at a large urban children's hospital with patients evaluated for fever at outpatient acute care visits during the peak period of MIS-C. Symptomatology and available objective data were extracted. Comparisons were performed using t tests with corrections for multiple comparisons, and multivariable logistic regression to obtain ORs. RESULTS: We identified 44 patients with MIS-C between April 16 and June 10, 2020. During the same period, 181 pediatric patients were evaluated for febrile illnesses in participating outpatient clinics. Patients with MIS-C reported greater median maximum reported temperature height (40°C vs 38.9, P
- Published
- 2021
25. Innate and adaptive dendritic cell responses to immunotherapy
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Pamela A. Frischmeyer-Guerrerio and Mark Gorelik
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medicine.medical_treatment ,Immunology ,Administration, Sublingual ,Administration, Oral ,T-Lymphocytes, Regulatory ,Article ,Immune tolerance ,Th2 Cells ,Immune system ,Immune Tolerance ,medicine ,Animals ,Humans ,Immunology and Allergy ,Peanut Hypersensitivity ,Immunosuppression Therapy ,B-Lymphocytes ,Innate immune system ,business.industry ,Innate lymphoid cell ,FOXP3 ,Forkhead Transcription Factors ,Dendritic Cells ,Immunotherapy ,Dendritic cell ,DNA Methylation ,Acquired immune system ,Desensitization, Immunologic ,Cytokines ,business - Abstract
Purpose of review In allergic disease, dendritic cells play a critical role in orchestrating immune responses to innate stimuli and promoting the formation of T helper 2 (TH2) effector versus T-regulatory cells. Here, we review recent advances in our understanding of how current forms of immunotherapy modulate dendritic cell responses. (Figure is included in full-text article.) Recent findings Sublingual immunotherapy (SLIT) and oral immunotherapy (OIT) for peanut allergy alter the expression of costimulatory molecules on dendritic cells, which leads to reduced expression of TH2 effector cytokines in an antigen-nonspecific manner. SLIT and OIT also modulate dendritic cell innate immune responses to Toll-like receptor agonists, including enhanced production of interferon α and reduced expression of proinflammatory cytokines that may serve to promote the development of tolerance. Dendritic cells isolated from patients post-OIT promoted hypomethylation of the FOXP3 locus in effector T cells. Reduced methylation of the FOXP3 locus has been associated with more persistent clinical desensitization following OIT. Recent studies have additionally highlighted a role for B cells in inducing tolerogenic dendritic cell populations and T-regulatory cells during immunotherapy. Epicutaneous immunotherapy may also elicit immunosuppressive populations of cutaneous dendritic cells, although in some cases, antigen exposure through the skin can lead to sensitization. Finally, efforts have focused on identifying pharmacologic and/or antigen-independent strategies of altering dendritic cell function to enhance the immunosuppressive effects of immunotherapy. Summary Dendritic cells are a critical target of immunotherapy. Alterations in both adaptive and innate immunity likely underlie the immunosuppressive effects of this treatment.
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- 2015
26. Follistatin-like Protein 1 and the Ferritin/Erythrocyte Sedimentation Rate Ratio Are Potential Biomarkers for Dysregulated Gene Expression and Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis
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Ndate Fall, Mark Gorelik, Mekibib Altaye, Michael G. Barnes, Raphael Hirsch, Susan D. Thompson, and Alexei A. Grom
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Male ,medicine.medical_specialty ,Follistatin-Related Proteins ,Immunology ,Gene Expression ,Arthritis ,Blood Sedimentation ,Peripheral blood mononuclear cell ,Article ,Rheumatology ,Internal medicine ,Gene expression ,medicine ,Humans ,Immunology and Allergy ,Child ,medicine.diagnostic_test ,biology ,business.industry ,Macrophage Activation Syndrome ,medicine.disease ,Arthritis, Juvenile ,Ferritin ,Endocrinology ,Child, Preschool ,Erythrocyte sedimentation rate ,Macrophage activation syndrome ,Ferritins ,biology.protein ,Erythropoiesis ,Female ,business ,Biomarkers ,Follistatin - Abstract
Objective.Follistatin-like protein 1 (FSTL-1) is a secreted glycoprotein overexpressed in certain inflammatory diseases. Our objective was to correlate FSTL-1 levels with gene expression, known biomarkers, and measures of disease activity in systemic juvenile idiopathic arthritis (sJIA), including macrophage activation syndrome (MAS).Methods.FSTL-1 serum levels were measured by ELISA in 28 patients with sJIA, including 7 patients who developed MAS, and 30 healthy controls. Levels were correlated with erythrocyte sedimentation rate (ESR), ferritin, and soluble interleukin-2 receptor-α (sIL-2Rα). Gene expression based on FSTL-1 levels was analyzed in peripheral blood mononuclear cells (PBMC).Results.Serum levels of FSTL-1 were elevated at time of presentation of sJIA (mean 200.7 ng/ml) and decreased to normal (mean 133.7 ng/ml) over 24 months (p < 0.01). FSTL-1 levels were markedly elevated during acute MAS (mean 279.8 ng/ml) and decreased to normal following treatment (p < 0.001). FSTL-1 levels correlated with serum markers of inflammation, including sIL-2Rα and ferritin. Ferritin/ESR ratio was superior to ferritin, sIL-2Rα, and FSTL-1 in discriminating MAS from new-onset sJIA. PBMC from patients with FSTL-1 levels > 200 ng/ml showed altered expression of genes related to innate immunity, erythropoiesis, and natural killer cell dysfunction. Two patients with the highest FSTL-1 levels at disease onset (> 300 ng/ml) ultimately developed MAS.Conclusion.Elevated pretreatment serum FSTL-1 levels in sJIA are associated with dysregulated gene expression suggestive of occult MAS, and may have utility in predicting progression to overt MAS. Ferritin/ESR ratio may be superior to ferritin alone in discriminating overt MAS from new-onset sJIA.
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- 2013
27. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Sublingual versus Oral Immunotherapy for the Treatment of Peanut Allergy
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Robert A. Wood, Corinne A. Keet, Robert G. Hamilton, Satya D. Narisety, Pamela A. Frischmeyer-Guerrerio, John T. Schroeder, and Mark Gorelik
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Male ,medicine.medical_specialty ,Oral immunotherapy ,Adolescent ,Arachis ,medicine.medical_treatment ,Immunology ,Peanut allergy ,Administration, Sublingual ,Administration, Oral ,Pilot Projects ,Placebo ,Article ,Food allergy ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Peanut Hypersensitivity ,Child ,Skin Tests ,Oral food challenge ,business.industry ,Immunotherapy ,Allergens ,Immunoglobulin E ,medicine.disease ,Slit ,Surgery ,Treatment Outcome ,Desensitization, Immunologic ,Immunoglobulin G ,Female ,business ,Off Treatment - Abstract
Although promising results have emerged regarding oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for the treatment of peanut allergy (PA), direct comparisons of these approaches are limited.This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut OIT and SLIT.In this double-blind study children with PA were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7 mg/d (SLIT) or 2000 mg/d (OIT), and subjects were rechallenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged.Twenty-one subjects aged 7 to 13 years were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a greater than 10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141- vs 22-fold, P = .01). Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found, with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT (P.001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion.OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects.
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- 2014
28. Suppression of the immunologic response to peanut during immunotherapy is often transient
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Pamela A. Frischmeyer-Guerrerio, Satya D. Narisety, Anja P. Bieneman, Corinne A. Keet, Anthony L. Guerrerio, Mark Gorelik, Kristin L. Chichester, John T. Schroeder, Robert G. Hamilton, and Robert A. Wood
- Subjects
Arachis ,medicine.medical_treatment ,T-Lymphocytes ,Immunology ,Peanut allergy ,Administration, Sublingual ,Administration, Oral ,Gene Expression ,Pilot Projects ,Basophil ,Article ,Immunology and Allergy ,Medicine ,Humans ,Peanut Hypersensitivity ,CD86 ,CD63 ,business.industry ,Tetraspanin 30 ,Dendritic cell ,Immunotherapy ,Dendritic Cells ,HLA-DR Antigens ,Allergens ,medicine.disease ,Basophils ,Basophil activation ,medicine.anatomical_structure ,Treatment Outcome ,Desensitization, Immunologic ,Cytokines ,Interleukin-4 ,business ,CD80 ,Biomarkers - Abstract
Background Studies suggest that oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood. Objective We sought to generate insights into the mechanisms and duration of suppression of immune responses to peanut during immunotherapy. Methods Blood was obtained from subjects at baseline and at multiple time points during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included measurement of spontaneous and stimulated basophil activity by using automated fluorometry (histamine) and flow cytometry (activation markers and IL-4), measurement of allergen-induced cytokine expression in dendritic cell (DC)–T-cell cocultures by using multiplexing technology, and measurement of MHC II and costimulatory molecule expression on DCs by using flow cytometry. Results Spontaneous and allergen-induced basophil reactivity (histamine release, CD63 expression, and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing. Peanut- and dust mite–induced expression of T H 2 cytokines was reduced in DC–T-cell cocultures during immunotherapy. This was associated with decreased levels of CD40, HLA-DR, and CD86 expression on DCs and increased expression of CD80. These effects were most striking in myeloid DC–T-cell cocultures from subjects receiving OIT. Many markers of immunologic suppression reversed after withdrawal from immunotherapy and in some cases during ongoing maintenance therapy. Conclusion OIT and SLIT for peanut allergy induce rapid suppression of basophil effector functions, DC activation, and T H 2 cytokine responses during the initial phases of immunotherapy in an antigen-nonspecific manner. Although there was some interindividual variation, in many patients suppression appeared to be temporary.
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- 2014
29. Follistatin like protein (FSTL-1) levels are elevated in acute Kawasaki Disease and may differentiate between patients with and without aneurysm formation
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Mark Gorelik, David O. Wilson, Stanford T. Shulman, and Raphael Hirsch
- Subjects
medicine.medical_specialty ,Pathology ,lcsh:Diseases of the musculoskeletal system ,Proinflammatory cytokine ,Rheumatology ,Internal medicine ,medicine ,Myocyte ,Immunology and Allergy ,cardiovascular diseases ,Pediatrics, Perinatology, and Child Health ,biology ,business.industry ,Mesenchymal stem cell ,lcsh:RJ1-570 ,lcsh:Pediatrics ,medicine.disease ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,biology.protein ,cardiovascular system ,Oral Presentation ,Kawasaki disease ,lcsh:RC925-935 ,Vasculitis ,business ,Artery ,Follistatin - Abstract
Purpose Kawasaki Disease is the most common vasculitis of childhood, and carries considerable morbidity with risk of development of coronary artery aneurysms. Serological predictors of the development of coronary artery aneurysms have not yet been found. FSTL-1 is a proinflammatory protein which is produced by mesenchymal tissue, including cardiac myocytes, and has been found to be elevated in inflammatory disorders such as Juvenile Idiopathic Arthri tis. The current study was designed to determine if plasma levels of FSTL-1 correlate with the development of Kawasaki Disease and development of coronary artery aneurysms. Methods
- Published
- 2012
30. Plasma follistatin-like protein 1 is elevated in Kawasaki disease and may predict coronary artery aneurysm formation
- Author
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David C. Wilson, Stanford T. Shulman, Yona K. Cloonan, Raphael Hirsch, and Mark Gorelik
- Subjects
Male ,medicine.medical_specialty ,Pathology ,Follistatin-Related Proteins ,Disease ,Mucocutaneous Lymph Node Syndrome ,Gastroenterology ,Article ,Enos ,Predictive Value of Tests ,Internal medicine ,Medicine ,Myocyte ,Humans ,Coronary artery aneurysm ,biology ,business.industry ,Coronary Aneurysm ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,Predictive value of tests ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,biology.protein ,Kawasaki disease ,Female ,business ,Artery ,Follistatin - Abstract
Objective To determine whether plasma levels of follistatin-like protein 1 (FSTL-1), a pro-inflammatory protein produced by mesenchymal tissue, including cardiac myocytes, correlate with the development of Kawasaki disease (KD) and coronary artery aneurysms (CAA). Study design FSTL-1 plasma levels were measured serially with enzyme-linked immunosorbent assay in 48 patients with KD at time of diagnosis and, when available, 2 weeks, 6 weeks, and 6 months after onset of disease. These were compared with FSTL-1 plasma levels in 23 control subjects. Data were analyzed with generalized estimating equations. Results Plasma FSTL-1 levels were elevated in patients with acute KD compared with control subjects ( P = .0086). FSTL-1 levels remained significantly elevated at 2 weeks after disease onset, but returned to control levels by 6 months. Seven patients with CAA had significantly higher FSTL-1 levels at the time of diagnosis than patients in whom aneurysms did not develop ( P = .0018). Sensitivity and specificity rates for CAA at a specific FSTL-1 cutoff point (178 ng/mL) were 85% and 71%. Conclusions Plasma levels of FSTL-1 are elevated in acute KD and may predict cardiac morbidity in this disease. These results suggest a possible role for FSTL-1 in the formation of CAAs.
- Published
- 2011
31. Impact of Sublingual and Oral Immunotherapy for Peanut Allergy on Blood Dendritic Cells
- Author
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Mark Gorelik, Satya Narisety, Anja P. Bieneman, Robert A. Wood, Anthony L. Guerrerio, Kristin L. Chichester, Pamela Frischmeyer Guerrerio, John T. Schroeder, Corinne A. Keet, and Robert G. Hamilton
- Subjects
Oral immunotherapy ,business.industry ,Immunology ,Peanut allergy ,medicine ,Immunology and Allergy ,medicine.disease ,business - Published
- 2015
32. Autoimmune hemolytic anemia with giant cell hepatitis: case report and review of the literature
- Author
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Mark, Gorelik, Robert, Debski, and Haydar, Frangoul
- Subjects
Antibodies, Monoclonal, Murine-Derived ,Treatment Outcome ,Antibodies, Monoclonal ,Humans ,Infant ,Antineoplastic Agents ,Female ,Anemia, Hemolytic, Autoimmune ,Rituximab ,Giant Cells ,Hepatitis - Abstract
Autoimmune hemolytic anemia (AIHA) with giant cell hepatitis (GCH) is an uncommon disease in children and is associated with an aggressive and often fatal course. The authors describe a 4-month-old girl who presented with AIHA and elevated liver enzymes. A liver biopsy was consistent with GCH. She was successfully treated with anti-CD20 antibody (rituximab)-containing therapy after failing initial immune suppression therapy. The authors also review the literature for similar cases.
- Published
- 2004
33. Hypocomplementemia Associated with Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis and Adult Onset Still’s Disease: 3 Cases: Table 1
- Author
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Kathryn S. Torok, Daniel A. Kietz, Mark Gorelik, and Raphael Hirsch
- Subjects
Systemic lupus erythematosus ,medicine.diagnostic_test ,business.industry ,Immunology ,Arthritis ,Still Disease ,medicine.disease ,Rheumatology ,Macrophage activation syndrome ,Erythrocyte sedimentation rate ,Intensive care ,medicine ,Immunology and Allergy ,Leukocytosis ,medicine.symptom ,business ,Juvenile rheumatoid arthritis - Abstract
To the Editor: Macrophage activation syndrome (MAS) is a life-threatening complication seen in association with childhood inflammatory diseases, most commonly in systemic juvenile idiopathic arthritis (sJIA)1,2,3. MAS has also been described in the setting of adult-onset Still’s disease (AOSD), systemic lupus erythematosus, drug reactions, and viral infections4,5. Decrease in C3 has been documented in patients with lupus and MAS4; however, to our knowledge, hypocomplementemia has not been previously described as associated with MAS in sJIA or AOSD. We describe 2 patients with sJIA, and a third with AOSD, who developed MAS with hypocomplementemia during the acute phase of illness. Patient 1, a 9-year-old boy, presented with high quotidian fever, evanescent rash, and arthritis. He had leukocytosis (24 × 109/l) with elevated markers of inflammation: erythrocyte sedimentation rate (ESR) 52 mm/h and C-reactive protein (CRP) 17.3 mg/dl. Liver enzymes and renal function were normal. Ferritin was 5623 ng/ml. Serologic tests for Epstein-Barr virus, parvovirus, cytomegalovirus, Lyme disease, mycoplasma, and group A streptococcus were negative. Complement levels, obtained by the primary intensive care team, showed slightly increased C3 (166 mg/dl) and normal C4 (32 mg/dl). He was discharged with a diagnosis of new-onset sJIA and prescribed indomethacin. Several days later, he returned to clinic with worsening symptoms and petechial … Address correspondence to Dr. Gorelik; E-mail: mark.gorelik{at}chp.edu
- Published
- 2011
34. Basophil Hyporesponsiveness To Peanut Following Immunotherapy May Be Transient and Correlates With Clinical Response
- Author
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Pamela Frischmeyer Guerrerio, Corinne A. Keet, Robert A. Wood, John T. Schroeder, Mark Gorelik, Anja P. Bieneman, Satya Narisety, and Kristin L. Chichester
- Subjects
medicine.anatomical_structure ,business.industry ,medicine.medical_treatment ,Immunology ,medicine ,Immunology and Allergy ,Immunotherapy ,Transient (oscillation) ,Basophil ,business - Published
- 2014
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