The latest medical research on Rheumatology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about rheumatology gathered by our medical AI research bot.

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Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

Annals of the Rheumatic Diseases

This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort.

Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions.

1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states.

Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

Single-cell transcriptomes and chromatin accessibility of endothelial cells unravel transcription factors associated with dysregulated angiogenesis in systemic sclerosis.

Annals of the Rheumatic Diseases

Vasculopathy emerges early in systemic sclerosis (SSc) and links to endothelial cell (EC) injury and angiogenesis. Understanding EC transcriptomes and epigenomes is crucial for unravelling the mechanisms involved.

Transcriptomes and chromatin accessibility were assessed by single-cell RNA sequencing and single-nucleus transposase-accessible chromatin sequencing. Immunofluorescent staining of skin and proteomics assay were employed to confirm the altered SSc EC phenotypes. Gain-of-function assay was used to evaluate the effects of ETS transcription factors on human dermal ECs (hDECs).

Both control and SSc ECs shared transcriptomic signatures of vascular linages (arterial, capillary and venous ECs) and lymphatic ECs. Arterial ECs in SSc showed reduced number and increased expression of genes associated with apoptosis. Two distinct EC subpopulations, tip and proliferating ECs, were markedly upregulated in SSc, indicating enhanced proangiogenic and proliferative activities. Molecular features of aberrant SSc-ECs were associated with disease pathogenesis and clinical traits of SSc, such as skin fibrosis and digital ulcers. Ligand-receptor analysis demonstrated altered intercellular networks of SSc EC subpopulations with perivascular and immune cells. Furthermore, the integration of open chromatin profiles with transcriptomic analysis suggested an increased accessibility of regulatory elements for ETS family transcription factors in SSc ECs. Overexpression of ETS genes in hDECs suggested ELK4, ERF and ETS1 may orchestrate arterial apoptosis and dysregulated angiogenesis in SSc.

This study unveils transcriptional and chromatin alterations in driving endovascular dysregulation in SSc, proposing ELK4, ERF and ETS1 as novel targets in ECs for addressing vascular complications in the condition.

Old before their time? The impact of osteoarthritis on younger adults.

Arthritis Care Res

Osteoarthritis (OA) is frequently perceived as a disease of the elderly and an inevitable result of aging. As OA studies often are restricted to older adults, there is limited information on OA in younger adults. This study describes the burden of OA across a wide age range and compares younger and older adults.

Descriptive analysis of the Survey on Living with Chronic Diseases in Canada - Arthritis Component, a nationally representative survey of Canadians aged 20+ years who reported an arthritis diagnosis in the Canadian Community Health Survey, a general health population survey. Analyses were restricted to those reporting OA and no other kind of arthritis (n=1,749).

In the representative group with OA, 55.4% were younger than 65. The mean age at diagnosis was 50 years, with 30.4% reporting being diagnosed before age 45. Younger adults reported similar symptom severity as their older counterparts with OA with regards to mean number of affected joint sites, severity of pain and fatigue, and activity limitations. In the youngest age group, those with OA were significantly more likely to report fair/poor overall and mental health and life dissatisfaction compared to their general population counterparts; the same was not the case in the oldest age group.

OA is not uncommon among younger and middle-aged adults, and they experience OA impacts comparable to those for older adults. This suggests that younger adults with OA will live many years with symptoms and disability, and highlights a need for effective OA management across ages.

Integrating Radiomics and Neural Networks for Knee Osteoarthritis Incidence Prediction.

Arthritis Rheumatol

Accurately predicting knee osteoarthritis (KOA) is essential for early detection and personalized treatment. We aimed to develop and test an MRI-based Joint Space Radiomic Model (JS-RM) to predict radiographic KOA incidence through neural networks by integrating meniscus and femorotibial cartilage radiomic features.

In the Osteoarthritis Initiative cohort, knees without radiographic KOA at baseline but at high risk for radiographic KOA were included. Case knees developed radiographic KOA whereas control knees did not over 4-year. We randomly split the knees into development and test cohorts (D/T=8/2) and extracted features from baseline 3D-DESS-sequence MRI. Model performance was evaluated using an area under the receiver operating characteristic curve (AUC), sensitivity, and specificity in both cohorts. Nine resident surgeons performed the reader experiment without/with the JS-RM aid.

Our study included 549 knees in the development cohort (275 cases vs. 274 controls) and 137 knees in the test cohort (68 cases vs. 69 controls). In the test cohort, JS-RM had a favorable accuracy for predicting the radiographic KOA incidence with an AUC of 0.931 (95%CI: 0.876-0.963), a sensitivity of 84.4% (95%CI: 83.9%-84.9%), and a specificity of 85.6% (95%CI: 85.2%-86.0%). The mean specificity and sensitivity of resident surgeons through MRI reading in predicting radiographic KOA incidence were increased from 0.474 (95%CI: 0.333-0.614) and 0.586 (95%CI: 0.429-0.743) without the assistance of JS-RM to 0.874 (95%CI: 0.847-0.901) and 0.812 (95%CI: 0.742-0.881) with JS-RM assistance, respectively (p<.001).

JS-RM integrating the features of the meniscus and cartilage showed improved predictive values in radiographic KOA incidence.

The American College of Rheumatology White Paper: The Effects of Climate Change on Rheumatic Conditions - An Evolving Landscape and a Path Forward.

Arthritis Rheumatol

Increases in global temperatures and extreme weather events associated with climate change have complex yet poorly understood detrimental impacts on human health. We reviewed the current published literature on climate change-related effects and rheumatic conditions.

To summarize our current understanding of the likely effects of climate change, including increased air pollution, on rheumatic disease, we searched the published, peer-reviewed English-language literature from January 2000-December 2022. Articles were reviewed by a team of rheumatologists and clinical and translational science researchers. Systematic review articles were not included but informed additional literature searches.

After extensive examination and adjudication, 88 articles met inclusion criteria and were selected for review. Much of the epidemiologic investigations assessed associations between air pollution and increased risk of development of rheumatoid arthritis, anti-citrullinated protein antibodies, flares of gout and hospitalizations for systemic lupus erythematosus. Increased heat vulnerability was associated with higher odds of recurrent hospitalizations across rheumatic conditions. Mechanisms for observed associations are poorly understood but could include the effects of epigenetic changes, oxidative stress, and inflammatory cytokines. Studies had limitations including restricted geography and populations studied without focus on historically marginalized communities at highest risk for adverse effects from pollution and climate change, the relative lack of mechanistic evaluations, and most with only indirect links to climate change.

To date, the published literature lacks studies that directly examine effects of climate change on rheumatic diseases. Collaborative translational and epidemiologic research is needed to enhance our understanding and awareness in this area.

Unveiling metabolic similarities of entheses in psoriasis and psoriatic arthritis patients using non-invasive in vivo imaging - results from the MAPSA study.

Arthritis Rheumatol

To assess and compare molecular tissue changes at the entheses in patients with psoriasis (PsO), psoriatic arthritis (PsA), and healthy controls (HC) in vivo using multispectral optoacoustic tomography (MSOT) and to describe their relationship with clinical and ultrasound findings of enthesitis.

A cross-sectional study (MAPSA) in bDMARD-naïve PsA and PsO patients and HC was performed. Participants underwent clinical, ultrasonographic and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, Achilles tendon attachment). MSOT-measured haemoglobin (Hb), oxygen saturation (SO2), collagen, and lipid levels were quantified and mean differences between groups were calculated using linear mixed-effects models. MSOT-measured analytes were compared between entheses with and without clinical and ultrasound anomalies.

Ninety participants were included (30 PsO, 30 PsA, 30 HC), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Both PsA and PsO patients showed increased oxygenated Hb (PsA: p=0.003; PsO: p=0.054) and SO2 (PsA: p<0.001; Pso: p=0.001) levels and decreased collagen signals (PsA: p<0.001; PsO: <0.001) compared to HC, with more pronounced changes in PsA. Significantly lower collagen levels (p=0.01) and increased lipids (p=0.03) were recorded in tender entheses compared to non-tender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO2 (p=0.014) and lipid signals (p=0.020), respectively.

PsA and PsO patients exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immuno-metabolic tissue changes.

Gout risk in adults with pre-diabetes initiating metformin.

Annals of the Rheumatic Diseases

Despite the strong association between gout and pre-diabetes, the role of metformin in gout among individuals with pre-diabetes remains uncertain. We compared the incidence rates of gout in adults with pre-diabetes starting metformin with those not using antidiabetic treatments.

We conducted a new-user, propensity score-matched cohort study using electronic health records from an academic health system (2007-2022). Pre-diabetes was defined based on haemoglobin A1c levels. Metformin users were identified and followed from the first metformin prescription date. Non-users of antidiabetic medications were matched to metformin users based on propensity score and the start of follow-up. The primary outcome was incident gout. Cox proportional hazards models estimated the HR for metformin. Linear regression analyses assessed the association between metformin use and changes in serum urate (SU) or C-reactive protein (CRP).

We identified 25 064 individuals with pre-diabetes and propensity score-matched 1154 metformin initiators to 13 877 non-users. Baseline characteristics were well balanced (all standardised mean differences <0.1). The median follow-up was 3.9 years. The incidence rate of gout per 1000 person-years was lower in metformin users 7.1 (95% CI 5.1 to 10) compared with non-users 9.5 (95% CI 8.8 to 10.2). Metformin initiation was associated with a reduced relative risk of gout (HR 0.68, 95% CI 0.48 to 0.96). No relationship was found between metformin and changes in SU or CRP.

Metformin use was associated with a reduced risk of gout among adults with pre-diabetes, suggesting that metformin may be important in lowering gout risk in individuals with pre-diabetes.

The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon.

Annals of the Rheumatic Diseases

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by antibodies to DNA (anti-DNA) and other nuclear macromolecule...

Patient research partner involvement in rheumatology research: a systematic literature review informing the 2023 updated EULAR recommendations for the involvement of patient research partners.

Annals of the Rheumatic Diseases

Patient research partners (PRPs) are people with a disease who collaborate in a research team as partners. The aim of this systematic literature review (SLR) was to assess barriers and facilitators to PRP involvement in rheumatology research.

The SLR was conducted in PubMed/Medline for articles on PRP involvement in rheumatology research, published between 2017 and 2023; websites were also searched in rheumatology and other specialties. Data were extracted regarding the definition of PRPs, their role and added value, as well as barriers and facilitators to PRP involvement. The quality of the articles was assessed. Quantitative data were analysed descriptively, and principles of thematic content analysis was applied to qualitative data.

Of 1016 publications, 53 articles were included; the majority of these studies were qualitative studies (26%), opinion articles (21%), meeting reports (17%) and mixed-methods studies (11%). Roles of PRPs ranged from research partners to patient advocates, advisors and patient reviewers. PRPs were reported/advised to be involved early in the project (32% of articles) and in all research phases (30%), from the conception stage to the implementation of research findings. The main barriers were challenges in communication and support for both PRPs and researchers. Facilitators of PRP involvement included more than one PRP per project, training of PRPs and researchers, a supportive environment for PRPs (including adequate communication, acknowledgement and compensation of PRPs) and the presence of a PRP coordinator.

This SLR identified barriers and facilitators to PRP involvement, and was key to updating the European Alliance of Associations for Rheumatology recommendations for PRP-researcher collaboration based on scientific evidence.

Blood RNA-sequencing across the continuum of ANA-positive autoimmunity reveals insights into initiating immunopathology.

Annals of the Rheumatic Diseases

Mechanisms underpinning clinical evolution to systemic lupus erythematosus (SLE) from preceding antinuclear antibodies (ANA) positivity are poorly understood. This study aimed to understand blood immune cell transcriptional signatures associated with subclinical ANA positivity, and progression or non-progression to SLE.

Bulk RNA-sequencing of peripheral blood mononuclear cells isolated at baseline from 35 ANA positive (ANA+) subjects with non-diagnostic symptoms was analysed using differential gene expression, weighted gene co-expression network analysis, deconvolution of cell subsets and functional enrichment analyses. ANA+ subjects, including those progressing to classifiable SLE at 12 months (n=15) and those with stable subclinical ANA positivity (n=20), were compared with 15 healthy subjects and 18 patients with SLE.

ANA+ subjects demonstrated extensive transcriptomic dysregulation compared with healthy controls with reduced CD4+naïve T-cells and resting NK cells, but higher activated dendritic cells. B-cell lymphopenia was evident in SLE but not ANA+ subjects. Two-thirds of dysregulated genes were common to ANA+ progressors and non-progressors. ANA+ progressors showed elevated modular interferon signature in which constituent genes were inducible by both type I interferon (IFN-I) and type II interferon (IFN-II) in vitro. Baseline downregulation of mitochondrial oxidative phosphorylation complex I components significantly associated with progression to SLE but did not directly correlate with IFN modular activity. Non-progressors demonstrated more diverse cytokine profiles.

ANA positivity, irrespective of clinical trajectory, is profoundly dysregulated and transcriptomically closer to SLE than to healthy immune function. Metabolic derangements and IFN-I activation occur early in the ANA+ preclinical phase and associated with diverging transcriptomic profiles which distinguish subsequent clinical evolution.

Recent advancements in cartilage tissue engineering innovation and translation.

Nature Reviews Rheumatology

Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhi...

Informing Digital Programs for Lupus Self-Management Education: A Systematic Scoping Review.

Arthritis Care Res

We describe the characteristics, content, and effectiveness of digital self-management (SM) education programs for lupus and other chronic conditions to identify gaps and inform the improvement of future programs in lupus.

Three bibliographic databases were searched for articles published between May 2012 and April 2022. The search was cast to capture the breadth of digital SM education programs in the following conditions: lupus, epilepsy, fibromyalgia, multiple sclerosis, sickle cell anemia, Sjogren's syndrome, psoriatic arthritis, and rheumatoid arthritis. Title and abstract screening, as well as full-text review, was conducted by two independent reviewers. Data extraction was first completed by one author charting all studies and then, a second time, by four members of the research team charting collaboratively.

Of the 1,969 articles identified through the search, 14 met inclusion criteria. Two additional articles were included following bibliography review. The 16 articles represented 12 unique digital SM education programs. Programs covered five conditions: epilepsy (n=3), fibromyalgia (n=2), multiple sclerosis (n=4), lupus (n=1), and rheumatoid arthritis (n=2). Most programs were asynchronous and internet-based (n=9) with a prescribed sequence of content (n=8). Peer, technical, or specialist support was offered in seven programs. Most programs demonstrated statistically significant improvement of symptoms in the intervention group (n=8).

This scoping review summarizes the current landscape for digital SM education programs in lupus and similar conditions. In lupus, further investigation will fill in the gaps around digital SM education needs, user experience and evaluation of outcomes.