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BMC Rheumatology Jun 2024Recent works in the scientific literature reported the role of C reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte...
Associations of C reactive protein to albumin ratio, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio with disease activity in patients with juvenile idiopathic arthritis.
INTRODUCTION
Recent works in the scientific literature reported the role of C reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as biomarkers of disease activity in rheumatic diseases.
OBJECTIVES
To investigate the role of CAR, PLR and NLR as potential markers of disease activity in children with non-systemic JIA (nsJIA) and their correlation with the risk of persistent disease activity of flare during follow up.
METHODS
Our prospective, cross-sectional study involved 130 nsJIA patients (74 with active disease and 56 with inactive disease according to Wallace criteria) and 62 healthy controls. Demographic, clinical and laboratory data were collected at baseline (T0) and at 3 (T1), 6 (T2), 12 (T3) and 18 months (T4) during follow up. Disease activity was evaluated through Juvenile Arthritis Disease Activity Score (JADAS-27).
RESULTS
At baseline, CRP and CAR were higher in patients than in controls (p = 0.046), while no differences were found for NLR and PLR. However, there was no positive correlation between CAR, NLR, PLR and JADAS-27 in JIA patients. To better investigate the role of CAR, NLR and PLR as markers of disease activity, we used a generalized estimating equation (GEE) model, applied to all patients either with or without active disease. According to this analysis, CAR and NLR baseline levels were predictive of higher risk of disease activity at 6 months follow up (p < 0.001).
CONCLUSIONS
CAR and NLR could indicate persistent disease activity in patients with JIA. Their predictive value could be increased by their combined use and by the observation of their trend during follow up, since increasing CAR values over time could predict a disease flare in the brief time.
PubMed: 38886765
DOI: 10.1186/s41927-024-00390-x -
ACR Open Rheumatology Jun 2024Identification of characteristics associated with active disease in juvenile idiopathic arthritis (JIA) could inform early disease treatment strategies. This study...
OBJECTIVE
Identification of characteristics associated with active disease in juvenile idiopathic arthritis (JIA) could inform early disease treatment strategies. This study evaluated characteristics associated with active disease at 12 and 24 months after JIA diagnosis in the era in which biologic disease-modifying antirheumatic drugs (DMARDs) became available for JIA.
METHODS
This single-center retrospective study from 2004 through 2018 assessed characteristics associated with active nonsystemic categories of JIA at 12 and 24 months after diagnosis. Relative prevalence (RP) of disease activity was evaluated in relation to prespecified characteristics. Using RP, the effect of increasing biologic DMARD availability on these predictors was assessed at 12 months.
RESULTS
A total of 1,151 patients with JIA were included. At 12 months, a 40% to 45% higher point prevalence of active disease was noted in older children (>5 years). Patients with active disease at 3 months had a greater prevalence of active disease at 12 months (RP 1.5, 95% confidence interval [CI] 1.2-1.8) and 24 months (RP 1.3, 95% CI 1-1.6). Compared to oligoarticular JIA, polyarticular RF-negative, psoriatic, and enthesitis-related JIA had a greater prevalence of active disease at 12 and 24 months. At 24 months, a greater prevalence of active disease was observed in children ≥10 years. RP of active disease was 25% lower in the late cohort (2013-2018) than in the earliest cohort (2004-2008; RP 0.75, 95% CI 0.62-0.92) when more biologic medications were available, but disease activity predictors were broadly similar over time.
CONCLUSION
Patients with JIA with active disease at 12 and 24 months were older at diagnosis, categorized as polyarticular RF-negative, psoriatic, or enthesitis-related JIA. Active disease at 3 months after diagnosis was associated with worse outcomes at 12 and 24 months.
PubMed: 38885948
DOI: 10.1002/acr2.11701 -
Health Expectations : An International... Jun 2024The aim of this study was to reveal the relationship between the health literacy (HL) levels of children with juvenile idiopathic arthritis (JIA) and their parents, and...
BACKGROUND
The aim of this study was to reveal the relationship between the health literacy (HL) levels of children with juvenile idiopathic arthritis (JIA) and their parents, and the general health status and physical performance of the children.
METHODS
This study included 79 children aged 9-18 years with a diagnosis of JIA and one of their parents. HL levels were evaluated with the Turkish version of the Health Literacy for School-Aged Children and Turkish Health Literacy-32 (THL-32) for children and Adult Health Literacy Scale (AHLS) for their parents. The Childhood Health Assessment Questionnaire (CHAQ), 6-minute walk test (6-MWT), 10-meter walking test (10-MWT) and 10-stair climbing test (10-SCT) was used to evaluate the children. Juvenile Arthritis Biopsychosocial Questionnaire (JAB-Q) was used to assess the children's and parents' psychosocial status and perception of health.
RESULTS
HL levels of patients with JIA were 16.5% low HL, %55.7 moderate HL and 27.8% high HL. According to THL-32 scale score, HL level of parents were as follows: inadequate, 3.8%; problematic, 22.8%; sufficient, 34.2%; and excellent, 39.2%. Children's HL levels increase positively as they get older, and no significant relationship was found with other parameters. The AHLS, CHAQ and JAB-Q scores were better in the group with higher education levels of the parents. No statistically significant association was found between the HL of the children and that of the parents.
CONCLUSION
In our study, it was found that the high education levels of the parents positively affected the quality of life and physical condition of their children and parental HL levels. In addition, it was shown that the HL levels of children with JIA were not statistically related to other parameters.
PATIENT OR PUBLIC CONTRIBUTION
Children diagnosed with JIA and one of their parents actively participated in the study. Feedback from children and families provided important information about obtaining and using HL information before and during the study. The importance of therapy programs and information focusing on the patient and their family, as well as the inter-multidisciplinary approach, in combating a chronic disease at an early age was reinforced by the feedback received from patients and their families.
Topics: Humans; Arthritis, Juvenile; Female; Male; Health Literacy; Child; Adolescent; Parents; Surveys and Questionnaires; Health Status; Turkey; Quality of Life
PubMed: 38879783
DOI: 10.1111/hex.14117 -
Frontiers in Immunology 2024Recurrent exposures to a pathogenic antigen remodel the CD8 T cell compartment and generate a functional memory repertoire that is polyclonal and complex. At the...
Recurrent exposures to a pathogenic antigen remodel the CD8 T cell compartment and generate a functional memory repertoire that is polyclonal and complex. At the clonotype level, the response to the conserved influenza antigen, M1 has been well characterized in healthy individuals, but not in patients receiving immunosuppressive therapy or with aberrant immunity, such as those with juvenile idiopathic arthritis (JIA). Here we show that patients with JIA have a reduced number of M1 specific RS/RA clonotypes, indicating decreased clonal richness and, as a result, have lower repertoire diversity. By using a rank-frequency approach to analyze the distribution of the repertoire, we found several characteristics of the JIA T cell repertoire to be akin to repertoires seen in healthy adults, including an amplified RS/RA-specific antigen response, representing greater clonal unevenness. Unlike mature repertoires, however, there is more fluctuation in clonotype distribution, less clonotype stability, and more variable IFNy response of the M1 specific RS/RA clonotypes in JIA. This indicates that functional clonal expansion is altered in patients with JIA on immunosuppressive therapies. We propose that the response to the influenza M1 epitope described here is a general phenomenon for JIA patients receiving immunosuppressive therapy, and that the changes in clonal richness and unevenness indicate a retarded and uneven generation of a mature immune response.
Topics: Humans; Arthritis, Juvenile; CD8-Positive T-Lymphocytes; Influenza Vaccines; Influenza, Human; Female; Child; Male; Adolescent; Vaccination; Clone Cells; Child, Preschool; Immunologic Memory; Young Adult
PubMed: 38873594
DOI: 10.3389/fimmu.2024.1306490 -
Frontiers in Pediatrics 2024Ophthalmopathy occurring in childhood can easily lead to irreversible visual impairment, and therefore a great deal of clinical and fundamental researches have been...
BACKGROUND
Ophthalmopathy occurring in childhood can easily lead to irreversible visual impairment, and therefore a great deal of clinical and fundamental researches have been conducted in pediatric ophthalmopathy. However, a few studies have been performed to analyze such large amounts of research using bibliometric methods. This study intended to apply bibliometric methods to analyze the research hotspots and trends in pediatric ophthalmopathy, providing a basis for clinical practice and scientific research to improve children's eye health.
METHODS
Publications related to pediatric ophthalmopathy were searched and identified in the Web of Science Core Collection (WoSCC) database. Bibliometric and visualized analysis was performed using the WoSCC analysis system and CiteSpace.6.2.6 software, and high-impact publications were analyzed.
RESULTS
This study included a total of 7,177 publications from 162 countries and regions. Of these, 2,269 from the United States and 1,298 from China. The centrality and H-index were highest in the United States at 0.27 and 66, respectively. The University of London and Harvard University had the highest H-index at 37. Freedman,Sharon F published 55 publications, with the highest H-index at 19. The emerging burst keyword in 2020-2023 was "eye tracking," and the burst keywords in 2021-2023 were "choroidal thickness," "pediatric ophthalmology," "impact" and "childhood glaucoma." Retinopathy of prematurity, myopia, retinoblastoma and uveitis in juvenile idiopathic arthritis were the main topics in the high-impact publications, with clinical studies in the majority, especially in retinopathy of prematurity.
CONCLUSION
Eye health in children is a research hotspot, with the United States publishing the largest number of papers and having the greatest influence in research on pediatric ophthalmopathy, and China coming in second. The University of London and Stanford University had the greatest influence. Freedman, Sharon F was the most influential author. Furthermore, "choroidal thickness," "pediatric ophthalmology," "impact," "childhood glaucoma" and "eye tracking"are the latest hotspots in the field of pediatric ophthalmopathy. These hotspots represent hot diseases, hot technologies and holistic concepts, which are exactly the research trends in the field of pediatric ophthalmopathy, providing guidance and grounds for clinical practice and scientific research on children's eye health.
PubMed: 38873588
DOI: 10.3389/fped.2024.1405110 -
Journal of the Korean Society of... May 2024Infections and inflammatory conditions of immature musculoskeletal systems in pediatric patients also affect the adjacent muscles, connective tissues, and joints. Rapid... (Review)
Review
Infections and inflammatory conditions of immature musculoskeletal systems in pediatric patients also affect the adjacent muscles, connective tissues, and joints. Rapid diagnosis leading to appropriate treatment can significantly impact the occurrence of complications and mortality rates due to these conditions. When a radiologist becomes familiar with the imaging findings of pediatric musculoskeletal infections and inflammatory diseases, rapid differential diagnoses and more timely and appropirate treatment could be possible. In this paper, we introduce the imaging findings of infectious and inflammatory diseases affecting the immature musculoskeletal system, such as osteomyelitis, pyogenic arthritis, juvenile idiopathic arthritis, and hemophilic arthritis, based on the anatomical and pathophysiological characteristics of the immature musculoskeletal system in children.
PubMed: 38873370
DOI: 10.3348/jksr.2024.0057 -
Annals of the Rheumatic Diseases Jun 2024We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.
OBJECTIVES
We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.
METHODS
Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0.
RESULTS
Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48.
CONCLUSIONS
In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48.
TRIAL REGISTRATION NUMBER
NCT01500551.
PubMed: 38849152
DOI: 10.1136/ard-2023-225094 -
Scientific Reports Jun 2024While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the...
While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.
Topics: Humans; Killer Cells, Natural; Lupus Erythematosus, Systemic; Female; Male; Adolescent; Child; Phenotype; Granzymes; Perforin; Apoptosis; Transcriptome; Gene Expression Profiling; Case-Control Studies
PubMed: 38844784
DOI: 10.1038/s41598-024-62325-3 -
The Lancet. Rheumatology Jul 2024For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to...
Outcomes after anti-tumour necrosis factor originator to biosimilar switching in children and young people with juvenile idiopathic arthritis in the UK: a national cohort study.
BACKGROUND
For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to biosimilars. Here, we aimed to investigate those who switched from an anti-tumour necrosis factor (TNF) originator to a biosimilar, regarding drug survival and disease activity, compared with a matched cohort who continued the originator.
METHODS
This analysis included all patients in the UK JIA Biologics Register switching directly from an anti-TNF originator to a biosimilar of the same product. All patients were matched (age, sex, disease duration, calendar year of when patients started originator therapy, line of therapy, and International League of Associations for Rheumatology [ILAR] category) to patients continuing the originator. For those matched successfully, a Cox proportional hazard model assessed whether drug persistence differed between those who switched compared with those who continued the originator. Overall change in the 71-joint juvenile arthritis disease activity score and the proportion of patients with a clinically important worsening score (by ≥1·7 units) after 6 months was compared between cohorts. This analysis was designed to address a priority research area set by our patient partners.
FINDINGS
There were 224 children and young people with non-systemic JIA (139 [62%] were female, and 85 [38%] were male) identified as switching from a biological originator to a biosimilar of the same product from Jan 1, 2017, to July 7, 2023. 143 (64%) patients were originally on adalimumab, 56 (25%) on etanercept, and 25 (11%) on infliximab. Of these, 164 patients were matched successfully to those continuing the originator. There was no evidence that patients switching were more likely to stop treatment compared with those continuing the originator, with a hazard ratio of 1·46 (95% CI 0·93-2·30). Of the 51 patients in the biosimilar group who stopped treatment, 18 (35%) switched back to the originator (14 in the first year), 28 (55%) started a different biological drug, and five (10%) discontinued all treatment by the last follow-up. Of the 87 matched patients with available disease activity, there was no evidence that JADAS-71 worsened more after 6 months, with an odds ratio of 0·71 (95% CI 0·34-1·51; p=0·38).
INTERPRETATION
In this matched comparative effectiveness analysis, children and young people with JIA switched from originators to biosimilars. Disease activity was similar between patients switching compared with those continuing the originator. Three quarters of patients were still receiving their biosimilar after 1 year, with switching back to originator uncommon, at only 9% after 1 year, suggesting good tolerability of non-medical switching in this patient population. This information is reassuring to clinicians and patients regarding the effect of non-medical biological switching.
FUNDING
British Society for Rheumatology, Versus Arthritis, and National Institutes for Health Research Manchester Biomedical Research Centre.
Topics: Humans; Arthritis, Juvenile; Male; Female; Biosimilar Pharmaceuticals; Child; Adolescent; Drug Substitution; Antirheumatic Agents; United Kingdom; Cohort Studies; Treatment Outcome; Child, Preschool; Tumor Necrosis Factor-alpha; Infliximab; Adalimumab; Etanercept; Biological Products
PubMed: 38843858
DOI: 10.1016/S2665-9913(24)00087-0 -
Frontiers in Immunology 2024Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite...
INTRODUCTION
Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity.
METHODS
A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level.
RESULTS
We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. , , , , , and were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels.
CONCLUSION
These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.
Topics: Humans; Arthritis, Juvenile; Female; Monocytes; Transcriptome; Gene Expression Profiling; Adolescent; Adult; Child; Male; Inflammation
PubMed: 38835762
DOI: 10.3389/fimmu.2024.1400036