17 results on '"Ruth NM"'
Search Results
2. The United States to Africa lupus prevalence gradient revisited
- Author
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Gilkeson, GS, primary, James, JA, additional, Kamen, DL, additional, Knackstedt, TJ, additional, Maggi, DR, additional, Meyer, AK, additional, and Ruth, NM, additional
- Published
- 2011
- Full Text
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3. Initial validation of the pediatric automated neuropsychological assessment metrics for childhood-onset systemic lupus erythematosus.
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Brunner HI, Ruth NM, German A, Nelson S, Passo MH, Roebuck-Spencer T, Ying J, and Ris D
- Published
- 2007
4. Efficacy and Safety of Pharmacokinetically-Driven Dosing of Mycophenolate Mofetil for the Treatment of Pediatric Proliferative Lupus Nephritis-A Double-Blind Placebo Controlled Clinical Trial (The Pediatric Lupus Nephritis Mycophenolate Mofetil Study).
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Sagcal-Gironella ACP, Merritt A, Mizuno T, Dharnidharka VR, McDonald J, DeGuzman M, Wahezi D, Goilav B, Onel K, Kim S, Cody E, Wu EY, Cannon L, Hayward K, Okamura DM, Patel PN, Greenbaum LA, Rouster-Stevens KA, Cooper JC, Ruth NM, Ardoin S, Cook K, Borgia RE, Hersh A, Huang B, Devarajan P, and Brunner H
- Abstract
Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability., Methods/design: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMF
PK , i.e. the dose is adjusted to the target area under the concentration-time curve (AUC0-12h ) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMFBSA , i.e. MMF dosed 600 mg/m2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMFBSA arm with PRR at week 26 will receive MMFPK from week 26 onwards, while subjects with CRR will continue MMFBSA or MMFPK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention., Discussion: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMFBSA and MMFPK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.- Published
- 2024
5. Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome.
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de Jesus AA, Chen G, Yang D, Brdicka T, Ruth NM, Bennin D, Cebecauerova D, Malcova H, Freeman H, Martin N, Svojgr K, Passo MH, Bhuyan F, Alehashemi S, Rastegar AT, Uss K, Kardava L, Marrero B, Duric I, Omoyinmi E, Peldova P, Lee CR, Kleiner DE, Hadigan CM, Hewitt SM, Pittaluga S, Carmona-Rivera C, Calvo KR, Shah N, Balascakova M, Fink DL, Kotalova R, Parackova Z, Peterkova L, Kuzilkova D, Campr V, Sramkova L, Biancotto A, Brooks SR, Manes C, Meffre E, Harper RL, Kuehn H, Kaplan MJ, Brogan P, Rosenzweig SD, Merchant M, Deng Z, Huttenlocher A, Moir SL, Kuhns DB, Boehm M, Skvarova Kramarzova K, and Goldbach-Mansky R
- Subjects
- Humans, Dasatinib, Inflammation metabolism, Neutrophils metabolism, Phosphorylation, Endothelial Cells metabolism, src-Family Kinases genetics, src-Family Kinases metabolism, Vasculitis genetics
- Abstract
Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life. Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN, p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. Functional studies revealed increased expression of ICAM-1 on induced patient-derived endothelial cells (iECs) and of β2-integrins on patient neutrophils that increase neutrophil adhesion and vascular transendothelial migration (TEM). Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. Our findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2023
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6. Health disparities in outcomes of pediatric systemic lupus erythematosus.
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Vara E, Gilbert M, and Ruth NM
- Abstract
Healthcare disparities exist throughout the United States, and disparities in healthcare delivery are responsible for a substantial portion of preventable morbidity and mortality. SLE disproportionately affects racial and ethnic minoritized groups, including Blacks, Hispanics, and Asians/Pacific Islanders. Specifically, Black females have a 3 to 4-fold increased risk of developing SLE than White females. Population studies funded through the Centers for Disease Control have examined variations in disease outcomes among the different populations around the United States. For example, studies have shown that lupus nephritis, anti-phospholipid syndrome, and thrombocytopenia are more likely to affect racial and ethnic minorities than Whites. In addition, the Center for Disease Control WONDER (Wide-ranging Online Data for Epidemiologic Research) database found SLE was the seventh leading cause of death for all women aged 15-25 years and the fifth leading cause of death for African American and Hispanic females. From these studies, we know SLE primarily affects racial and ethnic minorities, but we do not know why these groups are at increased risk of developing the disease or have worse outcomes. By examining the underlying mechanisms of health disparities within our patient populations and mitigation strategies, we will further understand and provide better treatment for our patients. This review will discuss current research related to health disparities and health outcomes in childhood-onset SLE (cSLE)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JC declared a shared committee with the author MG to the handling editor., (Copyright © 2022 Vara, Gilbert and Ruth.)
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- 2022
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7. International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis.
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Chalhoub NE, Wenderfer SE, Levy DM, Rouster-Stevens K, Aggarwal A, Savani SI, Ruth NM, Arkachaisri T, Qiu T, Merritt A, Onel K, Goilav B, Khubchandani RP, Deng J, Fonseca AR, Ardoin SP, Ciurtin C, Kasapcopur O, Jelusic M, Huber AM, Ozen S, Klein-Gitelman MS, Appenzeller S, Cavalcanti A, Fotis L, Lim SC, Silva RM, Miramontes JR, Rosenwasser NL, Saad-Magalhaes C, Schonenberg-Meinema D, Scott C, Silva CA, Enciso S, Terreri MT, Torres-Jimenez AR, Trachana M, Al-Mayouf SM, Devarajan P, Huang B, and Brunner HI
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- Adolescent, Age of Onset, Child, Female, Humans, Male, Retrospective Studies, Glucocorticoids administration & dosage, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic drug therapy, Lupus Nephritis etiology
- Abstract
Objective: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology., Methods: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%., Results: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6)., Conclusion: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials., (© 2021, American College of Rheumatology.)
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- 2022
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8. Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE.
- Author
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Gilbert M, Goilav B, Hsu JJ, Nietert PJ, Meidan E, Chua A, Ardoin SP, Wenderfer SE, von Scheven E, and Ruth NM
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- Antirheumatic Agents administration & dosage, Antirheumatic Agents adverse effects, Antirheumatic Agents classification, Attitude of Health Personnel, Child, Clinical Decision-Making, Consensus, Dose-Response Relationship, Immunologic, Drug Therapy, Combination methods, Expert Testimony, Humans, Lupus Nephritis immunology, Lupus Nephritis physiopathology, Lupus Nephritis urine, Medication Therapy Management, Recurrence, Surveys and Questionnaires, Lupus Nephritis drug therapy, Nephrologists, Pediatricians, Remission Induction methods, Rheumatologists, Rituximab administration & dosage, Rituximab adverse effects
- Abstract
Background: Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare., Methods: Members of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination., Results: Seventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15 % of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50 % agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59 % of nephrologists, but only 38 % of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58 % of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43 %) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p < 0.05)., Conclusions: Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN., (© 2021. The Author(s).)
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- 2021
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9. Formal neurocognitive function and anti-N-methyl-D-aspartate receptor antibodies in paediatric lupus.
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Nowling TK, Kral M, Wolf B, Gilkeson G, and Ruth NM
- Subjects
- Adolescent, Antibodies, Antinuclear, Autoantibodies, Child, Cross-Sectional Studies, Female, Humans, Male, Receptors, N-Methyl-D-Aspartate, Lupus Vasculitis, Central Nervous System
- Abstract
Objective: SLE is a chronic multisystem autoimmune inflammatory disease impacting a number of organs, including the central nervous system (CNS). The pathophysiology of CNS lupus is multifactorial, making diagnosis problematic. Neurocognitive (NC) testing and specific biomarkers to identify the development of neuropsychiatric (NP) symptoms in lupus are needed. Paediatric patients with SLE have high incidence of NP disease . While serum anti-N-methyl-D-aspartate receptor (NMDAR) antibodies have shown promise as a biomarker of NP in adults with SLE, much less is known with regard to paediatric patients with SLE., Methods: We performed a cross-sectional study in paediatric patients with SLE. Serum NMDAR antibodies were measured and compared with levels in patients with juvenile idiopathic arthritis (JIA). Formal NC testing was performed in accordance with the Childhood Arthritis & Rheumatology Research Alliance neuropsychological core test battery. NC functioning was compared in the two groups and with NMDAR antibody levels., Results: Serum NMDAR antibody levels were significantly higher in paediatric patients with SLE compared with patients with JIA. There were no significant correlations between NMDAR antibody levels and any measure of NC functioning. In an exploratory examination of anti-ribosomal P (RibP) antibody and NC functioning in a subset of patients with SLE, RibP antibody-positive patients exhibited worse scores for Verbal Memory Index and Design Fluency Test Switching compared with RibP antibody-negative patients. A globally significant association between disease status and NC functioning was observed. Specifically, patients with SLE had lower scores compared with patients with JIA for full-scale IQ, letter-word recognition, reading fluency and calculation skills after adjusting for multiple comparisons., Conclusion: These collective results suggest that although serum NMDAR may serve as a biomarker, formal NC testing is superior in identifying paediatric patients with SLE with NP manifestations. RibP also may potentially serve as a biomarker of NP manifestations in paediatric patients with SLE. Additional and longitudinal studies are needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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10. Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.
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de Jesus AA, Hou Y, Brooks S, Malle L, Biancotto A, Huang Y, Calvo KR, Marrero B, Moir S, Oler AJ, Deng Z, Montealegre Sanchez GA, Ahmed A, Allenspach E, Arabshahi B, Behrens E, Benseler S, Bezrodnik L, Bout-Tabaku S, Brescia AC, Brown D, Burnham JM, Caldirola MS, Carrasco R, Chan AY, Cimaz R, Dancey P, Dare J, DeGuzman M, Dimitriades V, Ferguson I, Ferguson P, Finn L, Gattorno M, Grom AA, Hanson EP, Hashkes PJ, Hedrich CM, Herzog R, Horneff G, Jerath R, Kessler E, Kim H, Kingsbury DJ, Laxer RM, Lee PY, Lee-Kirsch MA, Lewandowski L, Li S, Lilleby V, Mammadova V, Moorthy LN, Nasrullayeva G, O'Neil KM, Onel K, Ozen S, Pan N, Pillet P, Piotto DG, Punaro MG, Reiff A, Reinhardt A, Rider LG, Rivas-Chacon R, Ronis T, Rösen-Wolff A, Roth J, Ruth NM, Rygg M, Schmeling H, Schulert G, Scott C, Seminario G, Shulman A, Sivaraman V, Son MB, Stepanovskiy Y, Stringer E, Taber S, Terreri MT, Tifft C, Torgerson T, Tosi L, Van Royen-Kerkhof A, Wampler Muskardin T, Canna SW, and Goldbach-Mansky R
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- Female, Humans, Male, Autoimmune Diseases genetics, Autoimmune Diseases immunology, Interferon Type I genetics, Interferon Type I immunology, Interleukin-18 genetics, Interleukin-18 immunology, Macrophage Activation Syndrome genetics, Macrophage Activation Syndrome immunology, Mutation, Panniculitis genetics, Panniculitis immunology, Pulmonary Alveolar Proteinosis genetics, Pulmonary Alveolar Proteinosis immunology
- Abstract
BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.
- Published
- 2020
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11. FROSTED BRANCH ANGIITIS IN METHIMAZOLE-INDUCED ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-POSITIVE VASCULITIS.
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Koike KJ, Blice JP, Kylstra JA, Ralston JS, Self SE, Ruth NM, and Del Priore LV
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- Adolescent, Antithyroid Agents adverse effects, Behcet Syndrome complications, Behcet Syndrome immunology, Female, Fluorescein Angiography, Fundus Oculi, Humans, Retinal Vasculitis diagnosis, Retinal Vasculitis physiopathology, Antibodies, Antineutrophil Cytoplasmic immunology, Behcet Syndrome chemically induced, Methimazole adverse effects, Retinal Artery pathology, Retinal Vasculitis etiology, Visual Acuity
- Abstract
Purpose: To describe an unusual case of frosted branch angiitis that developed in a patient with acute onset systemic vasculitis possibly triggered by the antithyroid medication methimazole., Methods: We conducted a thorough review of the medical records of a 16-year-old female patient who presented with frosted branch angiitis. During the initial hospital admission, the patient underwent an extensive systemic workup to determine the etiology of her disease and ophthalmologic testing including fundus photographs and fluorescein angiography., Results: Our patient presented with a unilateral acute onset loss of vision, whose fundus examination revealed the pathognomonic features of frosted branch angiitis. Extensive systemic workup revealed an antineutrophilic cytoplasmic antibody-positive vasculitis, possibly triggered by methimazole., Conclusion: This case is the first reported frosted branch angiitis associated with a drug-induced antineutrophilic cytoplasmic antibody-positive vasculitis triggered by methimazole.
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- 2018
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12. Advances in the care of children with lupus nephritis.
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Wenderfer SE, Ruth NM, and Brunner HI
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- Biopsy, Child, Child, Preschool, Female, History, 20th Century, History, 21st Century, Humans, Immunosuppressive Agents, Kidney pathology, Lupus Erythematosus, Systemic diagnosis, Lupus Nephritis history, Male, Pediatrics history, Pediatrics methods, Prognosis, Biomarkers metabolism, Lupus Nephritis therapy
- Abstract
The care of children with lupus nephritis (LN) has changed dramatically over the past 50 y. The majority of patients with childhood-onset systemic lupus erythematosus (cSLE) develop LN. In the 1960's, prognosis in children was worse than in adults; therapies were limited and toxic. Nearly half of cases resulted in death within 2 y. Since this time, several diagnostic recommendations and disease-specific indices have been developed to assist physicians caring for patients with LN. Pediatric researchers are validating and adapting these indices and guidelines for the treatment of LN in cSLE. Classification systems, activity, and chronicity indices for kidney biopsy have been validated in pediatric cohorts in several countries. Implementation of contemporary immunosuppressive agents has reduced treatment toxicity and improved outcomes. Biomarkers sensitive to LN in children have been identified in the kidney, urine, and blood. Multi-institutional collaborative networks have formed to address the challenges of pediatric LN research. Considerable variation in evaluation and treatment has been addressed for proliferative forms of LN by development of consensus treatment practices. Patient survival at 5 y is now 95-97% and renal survival exceeds 90%. Moreover, international consensus exists for quality indicators for cSLE that consider the unique aspects of chronic disease in childhood.
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- 2017
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13. Cognitive Performance Scores for the Pediatric Automated Neuropsychological Assessment Metrics in Childhood-Onset Systemic Lupus Erythematosus.
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Vega-Fernandez P, Vanderburgh White S, Zelko F, Ruth NM, Levy DM, Muscal E, Klein-Gitelman MS, Huber AM, Tucker LB, Roebuck-Spencer T, Ying J, and Brunner HI
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- Adolescent, Age of Onset, Algorithms, Area Under Curve, Child, Cognition Disorders etiology, Female, Humans, Male, ROC Curve, Cognition Disorders diagnosis, Lupus Erythematosus, Systemic psychology, Neuropsychological Tests
- Abstract
Objective: To develop and initially validate a global cognitive performance score (CPS) for the Pediatric Automated Neuropsychological Assessment Metrics (PedANAM) to serve as a screening tool of cognition in childhood lupus., Methods: Patients (n = 166) completed the 9 subtests of the PedANAM battery, each of which provides 3 principal performance parameters (accuracy, mean reaction time for correct responses, and throughput). Cognitive ability was measured by formal neurocognitive testing or estimated by the Pediatric Perceived Cognitive Function Questionnaire-43 to determine the presence or absence of neurocognitive dysfunction (NCD). A subset of the data was used to develop 4 candidate PedANAM-CPS indices with supervised or unsupervised statistical approaches: PedANAM-CPSUWA , i.e., unweighted averages of the accuracy scores of all PedANAM subtests; PedANAM-CPSPCA , i.e., accuracy scores of all PedANAM subtests weighted through principal components analysis; PedANAM-CPSlogit , i.e., algorithm derived from logistic models to estimate NCD status based on the accuracy scores of all of the PedANAM subtests; and PedANAM-CPSmultiscore , i.e., algorithm derived from logistic models to estimate NCD status based on select PedANAM performance parameters. PedANAM-CPS candidates were validated using the remaining data., Results: PedANAM-CPS indices were moderately correlated with each other (|r| > 0.65). All of the PedANAM-CPS indices discriminated children by NCD status across data sets (P < 0.036). The PedANAM-CPSmultiscore had the highest area under the receiver operating characteristic curve (AUC) across all data sets for identifying NCD status (AUC >0.74), followed by the PedANAM-CPSlogit , the PedANAM-CPSPCA , and the PedANAM-CPSUWA , respectively., Conclusion: Based on preliminary validation and considering ease of use, the PedANAM-CPSmultiscore and the PedANAM-CPSPCA appear to be best suited as global measures of PedANAM performance., (© 2015, American College of Rheumatology.)
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- 2015
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14. Practice patterns and approach to kidney biopsy in lupus: a collaboration of the Midwest Pediatric Nephrology Consortium and the Childhood Arthritis and Rheumatology Research Alliance.
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Wenderfer SE, Lane JC, Shatat IF, von Scheven E, and Ruth NM
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- Biopsy, Child, Cooperative Behavior, Data Collection, Humans, Midwestern United States, Nephritis pathology, Nephrology, Rheumatology, Societies, Medical, Specialization, Kidney pathology, Lupus Erythematosus, Systemic complications, Nephritis diagnosis, Nephritis etiology, Practice Patterns, Physicians'
- Abstract
Background: There is no clear consensus regarding optimal indications or timing of initial or repeat kidney biopsy in the management of pediatric systemic lupus erythematosus (pSLE)., Methods: A web-based survey was designed to assess current practice patterns among pediatric nephrologists and pediatric rheumatologists and distributed to members of Midwest Pediatric Nephrology Consortium (MWPNC) and Childhood Arthritis and Rheumatology Research Alliance (CARRA)., Results: Respondents included 111 rheumatologists and 71 nephrologists from 65 and 34 centers, respectively. Numbers of years in sub-specialty practice were comparable. Rheumatologists and nephrologists frequently collaborate in the care of children with lupus nephritis (LN). More than 90% of respondents refer patients to each either other after diagnosing LN. Over 60% describe shared decision making regarding when to perform kidney biopsy and how to interpret biopsy findings. Many pediatric nephrologists consider biopsy to be of higher risk for complication in pSLE and alter their standard pre-or post-biopsy management., Conclusions: It is uncommon for pediatric nephrologists to manage LN without input from pediatric rheumatologists and vice versa. Consensus exists between specialties in general, and practice differences that exist occur between individual physicians rather than between specialties. A systematic approach to biopsy may result in improved health related outcomes in pSLE.
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- 2015
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15. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis.
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Ilowite NT, Prather K, Lokhnygina Y, Schanberg LE, Elder M, Milojevic D, Verbsky JW, Spalding SJ, Kimura Y, Imundo LF, Punaro MG, Sherry DD, Tarvin SE, Zemel LS, Birmingham JD, Gottlieb BS, Miller ML, O'Neil K, Ruth NM, Wallace CA, Singer NG, and Sandborg CI
- Subjects
- Adolescent, Antirheumatic Agents adverse effects, Child, Child, Preschool, Double-Blind Method, Female, Humans, Male, Recombinant Fusion Proteins adverse effects, Treatment Outcome, Antirheumatic Agents therapeutic use, Arthritis, Juvenile drug therapy, Recombinant Fusion Proteins therapeutic use
- Abstract
Objective: To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial., Methods: An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria., Results: The time to response was shorter in the rilonacept arm than in the placebo arm (χ(2) = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idiopathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study., Conclusion: Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA., (Copyright © 2014 by the American College of Rheumatology.)
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- 2014
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16. Juvenile idiopathic arthritis: management and therapeutic options.
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Ruth NM and Passo MH
- Abstract
THE GOALS OF TREATMENT FOR JUVENILE IDIOPATHIC ARTHRITIS (JIA) INCLUDE: suppression of inflammation, achievement of remission, relief of pain, maintenance of function and doing so with minimal toxicity. Important discoveries over the past 10-15 years have led to more targeted treatments for children with JIA. The International League of Associations for Rheumatology (ILAR) classification system for childhood arthritides, better assessment tools for clinical response, improved definitions of remission, new imaging techniques and evidence in gene expression profiling have all contributed to the development of more targeted treatments. Nonsteroidal anti-inflammatory agents still have a role in mild disease and intra-articular steroid injections continue to be used most commonly in patients with oligoarticular JIA. Disease-modifying agents such as methotrexate have demonstrated efficacy and safety; however, in many patients, the disease remains active despite this treatment. These children now receive more targeted treatment including the tumor necrosis factor alpha (TNFα) inhibitors, interleukin-1 blockade, interleukin-6 blockade, selective costimulation modulators and selective B-cell blockade. The biologic targeted therapies have changed the strategy in which we treat our children with JIA; however, there remains much to be learned about the long-term effects and safety of these medicines.
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- 2012
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17. Pediatric clinical research.
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Lovell DJ and Ruth NM
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- Arthritis, Juvenile diagnosis, Arthritis, Juvenile therapy, Child, Dermatomyositis diagnosis, Dermatomyositis therapy, Humans, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic therapy, Pediatrics, Biomedical Research methods
- Abstract
Purpose of Review: This review will focus on childhood-onset systemic lupus erythematosus, juvenile idiopathic arthritis, and juvenile dermatomyositis, with special interest on strategies to improve the health-related quality of life in these conditions., Recent Findings: The contribution of plasma insulin levels, lipoproteins, markers of oxidized state (including nitric oxide metabolites, isoprostanes) and autoantibodies to oxidized low-density lipoprotein to risk for atherosclerosis has been studied in childhood-onset systemic lupus erythematosus. Elevated serum levels of myeloid-related protein-8 (also called S100A8) and myeloid-related protein-14 (S100A9) in children with juvenile idiopathic arthritis can indicate clinically occult disease activity. Serum levels of S100A12 correlate with disease activity in juvenile idiopathic arthritis. Magnetic resonance imaging T2 relaxation times in weight-bearing cartilage in patients with juvenile idiopathic arthritis may help with early detection of cartilage changes. Quantitative computed tomography commonly shows decreased muscle mass and abnormal bone geometry in juvenile idiopathic arthritis patients. In patients with juvenile idiopathic arthritis who do not respond to oral methotrexate, subcutaneous methotrexate dosing was frequently successful. Duration of inactive disease while a patient is receiving methotrexate does not decrease the frequency of flaring of disease once methotrexate is discontinued. Residual synovial inflammation seems to be a stronger influence on the rate of relapse. In juvenile dermatomyositis, the quantitative magnetic resonance imaging T2 relaxation time and overexpression of Class I major histocompatibility complex in early juvenile dermatomyositis are reported. Intravenous cyclophosphamide in refractory juvenile dermatomyositis and tacrolimus ointment for the dermatologic manifestations of juvenile dermatomyositis seem promising., Summary: Progress has been made in the diagnosis and treatment of childhood-onset systemic lupus erythematosus, juvenile idiopathic arthritis, and juvenile dermatomyositis.
- Published
- 2005
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