Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis part 2: results of the Nordic model in the Canadian cohort

Abstract Background Models to predict disease course and long-term outcome based on clinical characteristics at disease onset may guide early treatment strategies in juvenile idiopathic arthritis (JIA). Before a prediction model can be recommended for use in clinical practice, it needs to be validated in a different cohort than the one used for building the model. The aim of the current study was to validate the predictive performance of the Canadian prediction model developed by Guzman et al. and the Nordic model derived from Rypdal et al. to predict severe disease course and non-achievement of remission in Nordic patients with JIA. Methods The Canadian and Nordic multivariable logistic regression models were evaluated in the Nordic JIA cohort for prediction of non-achievement of remission, and the data-driven outcome denoted severe disease course. A total of 440 patients in the Nordic cohort with a baseline visit and an 8-year visit were included. The Canadian prediction model was first externally validated exactly as published. Both the Nordic and Canadian models were subsequently evaluated with repeated fine-tuning of model coefficients in training sets and testing in disjoint validation sets. The predictive performances of the models were assessed with receiver operating characteristic curves and C-indices. A model with a C-index above 0.7 was considered useful for clinical prediction. Results The Canadian prediction model had excellent predictive ability and was comparable in performance to the Nordic model in predicting severe disease course in the Nordic JIA cohort. The Canadian model yielded a C-index of 0.85 (IQR 0.83–0.87) for prediction of severe disease course and a C-index of 0.66 (0.63–0.68) for prediction of non-achievement of remission when applied directly. The median C-indices after fine-tuning were 0.85 (0.80–0.89) and 0.69 (0.65–0.73), respectively. Internal validation of the Nordic model for prediction of severe disease course resulted in a median C-index of 0.90 (0.86–0.92). Conclusions External validation of the Canadian model and internal validation of the Nordic model with severe disease course as outcome confirm their predictive abilities. Our findings suggest that predicting long-term remission is more challenging than predicting severe disease course.

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Predicting Which Children with Juvenile Idiopathic Arthritis Will Have a Severe Disease Course: Results from the ReACCh-Out Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.160197 ◽

2016 ◽

Vol 44 (2) ◽

pp. 230-240 ◽

Cited By ~ 22

Author(s):

Jaime Guzman ◽

Andrew Henrey ◽

Thomas Loughin ◽

Roberta A. Berard ◽

Natalie J. Shiff ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Prediction Models ◽

Severe Disease ◽

Inactive Disease ◽

Joint Involvement ◽

Disease Course ◽

Active Joint ◽

Random Samples ◽

Patient Reported ◽

Distinct Disease

Objective.We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis.Methods.Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included. Multivariable cluster analysis, r2, and silhouette statistics were used to identify distinct disease courses. One hundred candidate prediction models were developed in random samples of 75% of the cohort; their reliability and accuracy were tested in the 25% not used in their development.Results.Four distinct courses were identified in 609 subjects. They differed in prioritized variables, disability scores, and probabilities of attaining inactive disease and remission. We named them Mild (43.8% of children), Moderate (35.6%), Severe Controlled (9%), and Severe Persisting (11.5%). A logistic regression model using JIA category, active joint count, and pattern of joint involvement at enrollment best predicted a severe disease course (Controlled + Persisting, c-index = 0.87); 91% of children in the highest decile of risk actually experienced a severe disease course, compared to 5% of those in the lowest decile.Conclusion.Children in this JIA cohort followed 1 of 4 disease courses and the probability of a severe disease course could be estimated with information available at diagnosis.

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Faculty Opinions recommendation of Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis part 2: results of the Nordic model in the Canadian cohort.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737223500.793582484 ◽

2021 ◽

Author(s):

Elizabeth Mellins

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Prediction Models ◽

Severe Disease ◽

Disease Course

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Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽

10.3390/v13030514 ◽

2021 ◽

Vol 13 (3) ◽

pp. 514

Author(s):

Denise Utami Putri ◽

Cheng-Hui Wang ◽

Po-Chun Tseng ◽

Wen-Sen Lee ◽

Fu-Lun Chen ◽

...

Keyword(s):

Immune Response ◽

Immune Cells ◽

Mononuclear Cells ◽

Immune Cell ◽

Severe Disease ◽

Viral Rna ◽

Disease Course ◽

Peripheral Blood Mononuclear ◽

Peripheral Immune Cells ◽

Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

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Developing and validating COVID-19 adverse outcome risk prediction models from a bi-national European cohort of 5594 patients

Scientific Reports ◽

10.1038/s41598-021-81844-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Espen Jimenez-Solem ◽

Tonny S. Petersen ◽

Casper Hansen ◽

Christian Hansen ◽

Christina Lioma ◽

...

Keyword(s):

Prediction Models ◽

Severe Disease ◽

External Validation ◽

Area Under The Curve ◽

Predictive Performance ◽

Mortality Prediction ◽

Icu Admission ◽

Risk Of Death ◽

Online Risk ◽

The United Kingdom

AbstractPatients with severe COVID-19 have overwhelmed healthcare systems worldwide. We hypothesized that machine learning (ML) models could be used to predict risks at different stages of management and thereby provide insights into drivers and prognostic markers of disease progression and death. From a cohort of approx. 2.6 million citizens in Denmark, SARS-CoV-2 PCR tests were performed on subjects suspected for COVID-19 disease; 3944 cases had at least one positive test and were subjected to further analysis. SARS-CoV-2 positive cases from the United Kingdom Biobank was used for external validation. The ML models predicted the risk of death (Receiver Operation Characteristics—Area Under the Curve, ROC-AUC) of 0.906 at diagnosis, 0.818, at hospital admission and 0.721 at Intensive Care Unit (ICU) admission. Similar metrics were achieved for predicted risks of hospital and ICU admission and use of mechanical ventilation. Common risk factors, included age, body mass index and hypertension, although the top risk features shifted towards markers of shock and organ dysfunction in ICU patients. The external validation indicated fair predictive performance for mortality prediction, but suboptimal performance for predicting ICU admission. ML may be used to identify drivers of progression to more severe disease and for prognostication patients in patients with COVID-19. We provide access to an online risk calculator based on these findings.

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Hip osteoarthritis in juvenile idiopathic arthritis is complication of the disease course or side effect of systemic glucocorticosteroid treatment?

Bone Reports ◽

10.1016/j.bonr.2021.100940 ◽

2021 ◽

Vol 14 ◽

pp. 100940

Author(s):

Lubov Sorokina ◽

Ilia Avrusin ◽

Rinat Raupov ◽

Sergey Khrypov ◽

Mikhail Kostik

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Side Effect ◽

Hip Osteoarthritis ◽

Disease Course

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High levels of transaminases at admission predict a severe disease course in COVID-19 hospitalized patients

Digestive and Liver Disease ◽

10.1016/j.dld.2020.12.058 ◽

2021 ◽

Vol 53 ◽

pp. S22

Author(s):

F. Pelizzaro ◽

M.P. Kitenge ◽

F. Maran ◽

E. Cocconcelli ◽

E. Balestro ◽

...

Keyword(s):

Severe Disease ◽

Hospitalized Patients ◽

Disease Course

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AB0980 CASE-REVIEW ON FAMILIAL MEDITERRANEAN FEVER IN A SPECIALIZED CENTRE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1355 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1784.1-1784

Author(s):

R. Dos Santos Sobrín ◽

M. Martí Masanet ◽

B. Lopez-Montesinos ◽

L. Lacruz Pérez ◽

I. Calvo

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Familial Mediterranean Fever ◽

Periodic Fever ◽

Severe Disease ◽

Strong Association ◽

Mefv Gene ◽

Systemic Juvenile Idiopathic Arthritis ◽

Case Series ◽

Case Review ◽

Mediterranean Fever

Background:Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder caused mostly by mutations in MEFV gene. Its inheritance is autosomal recessive and is the most frequent periodic fever syndrome. First-line treatment is based in colchicine use, so biologics (anti-IL-1) are reserved for refractory cases1, 2.Objectives:To account for clinic and treatment features of patients with FMF in a specialized center as opposed to non-referent centers.Methods:This study was developed in the Pediatric Rheumatology Service in Hospital Universitario y Politécnico La Fe de Valencia. Demographic, clinic and treatment data were collected from patients diagnosed of FMF since January 2004 to September 2019.Results:106 patients met last FMF criteria3. 55% had a pathogenic mutation in genetic analysis. 52% were female. Before 10 years old, 71% of patients had the diagnosis (51% before 4 years old). Arthralgia/myalgia (73%), periodic fever (62%) and abdominal pain (54%) were the most common symptoms. Systemic Juvenile Idiopathic Arthritis (JIA, 6), other forms of JIA (9) and vasculitis (10) were the most prevalent comorbidities. When talking about treatment, 76,4% received Colchicine (60,5% with good response), 22,6% needed a classical disease modifying antirheumatic drug (mostly Methotrexate) and 22 patients got biologic treatment (73% anti-IL-1).Conclusion:When analyzing this case-review, JIA has a strong association with our patients, so it could explain severe disease activity and more articular involvement. This could be an illustration to the higher use of Methotrexate. Also, the most relevant symptom was arthralgia while fever is the most frequent in literature. Likewise, age of diagnosis has been earlier than other case-series (this would be more frequent in other autoinflammatory syndromes, as literature relates)1, 2, 4.References:[1]Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. (2019).[2]Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644-651.[3]Sag E, Demirel D, Demir S, et al. Performance of the new “Eurofever/PRINTO classification criteria” in FMF patients. Semin Arthritis Rheum. 2019;19:30369-5.[4]Rozenbaum M, Rosner I. Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clin Exp Rheumatol. 2004;22:S75-8.Disclosure of Interests:Raquel Dos Santos Sobrín: None declared, Miguel Martí Masanet: None declared, B Lopez-Montesinos: None declared, Lucía Lacruz Pérez: None declared, Inmaculada Calvo Grant/research support from: Bristol-Myers Squibb, Clementia, GlaxoSmithKline, Hoffman-La Roche, Merck Sharpe & Dohme, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, GlaxoSmithKline, Hoffman-La Roche, Novartis

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Pathological findings in rotation thromboelastometry associated with thromboembolic events in COVID-19 patients

Thrombosis Journal ◽

10.1186/s12959-021-00263-0 ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Kristina Boss ◽

Andreas Kribben ◽

Bartosz Tyczynski

Keyword(s):

Severe Sepsis ◽

Severe Disease ◽

Study Data ◽

Sepsis Group ◽

Similar Data ◽

Disease Course ◽

Thromboembolic Events ◽

Pathological Findings ◽

Fibrinolysis Shutdown ◽

Maximum Clot Firmness

Abstract Background Severe thromboembolic events are one of the major complications associated with COVID-19 infection, especially among critically ill patients. We analysed ROTEM measurements in COVID-19 patients with a severe disease course and in patients with severe sepsis. Methods In this study, data obtained by extended analysis of haemostasis with standard laboratory tests and thromboelastometry of 20 patients with severe course of COVID-19 were retrospectively analysed and compared with similar data from 20 patients with severe sepsis but no COVID-19. Results The thromboelastometry values obtained from 20 sepsis patients contained a maximum clot firmness above the normal range but among COVID-19 patients, hypercoagulability was much more pronounced, with significantly higher maximum clot firmness (FIBTEM: 38.4 ± 10.1 mm vs. 29.6 ± 10.8 mm; P = 0.012; EXTEM: 70.4 ± 10.4 mm vs. 60.6 ± 14.8 mm; P = 0.022). Additionally, fibrinogen levels were significantly higher among COVID-19 patients (757 ± 135 mg/dl vs. 498 ± 132 mg/dl, P < 0.0001). Furthermore, thromboelastometry showed fibrinolysis shutdown among COVID-19 patients with significantly lower maximum of lysis than among sepsis patients (EXTEM: 0.6 ± 1.2 % vs. 3.3 ± 3.7 %; P = 0.013). Seven of 20 COVID-19 patients experienced thromboembolic events, whereas no patient in the sepsis group experienced such events. Conclusions ROTEM analysis showed significantly different pathological findings characterized by hypercoagulability and fibrinolysis shutdown among COVID-19 patients with a severe disease course compared to patients with severe sepsis. These abnormalities seem to be associated with thromboembolic events.

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Lipopolysaccharide stimulation test on cultured PBMCs assists the discrimination of cryopyrin-associated periodic syndrome from systemic juvenile idiopathic arthritis

Scientific Reports ◽

10.1038/s41598-021-91354-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chao-Yi Wu ◽

Wen-Lang Fan ◽

Ying-Ming Chiu ◽

Huang-Yu Yang ◽

Wen-I. Lee ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Inflammatory Cytokines ◽

Mononuclear Cells ◽

Systemic Juvenile Idiopathic Arthritis ◽

Periodic Syndrome ◽

Disease Course ◽

Peripheral Blood Mononuclear ◽

Persistent Disease ◽

Caspase 1 ◽

Stimulation Tests

AbstractSystemic juvenile idiopathic arthritis (sJIA) and cryopyrin-associated periodic syndrome (CAPS) share many common manifestations. We aim to identify an applicable method to assist disease discrimination. Inflammatory cytokines were measured in the plasma of patients with CAPS, sJIA with persistent disease course and healthy controls. Supernatants collected from non-stimulated peripheral blood mononuclear cells (PBMCs) and those undergone inflammasome stimulation tests utilizing lipopolysaccharide (LPS) with and without adenosine triphosphate (ATP) were investigated. Inflammatory cytokines in patient plasma fail to differentiate sJIA from CAPS. PBMCs from sJIA secrets higher amount of IL-1β and IL-18 while CAPS PBMCs produces more caspase-1 without stimulation. IL-1β, IL-18, and caspase-1 were significantly elevated among CAPS PBMCs (all p < 0.05) upon LPS stimulation, but not when additional ATPs were provided. Levels of cytokines and PBMC responses to the stimulation assays were similar among all sJIA patients regardless of their history of macrophage activation syndrome. Unstimulated PBMC activities and the LPS inflammasome stimulation assay without exogenic ATPs can assist the differentiation of CAPS from sJIA with persistent disease course.

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