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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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.

Prevalence of Fibromyalgia and Widespread Pain in Psoriatic Arthritis: Association with Disease Severity Assessment in a Large US Registry.

Arthritis Care Res

The classic conception of pain etiology in rheumatologic disease is nociceptive pain - tissue injury and inflammation signaling through peripheral and central nerve fibers. But this can be mixed with other pain etiologies, including nociplastic, augmented pain experience due to central sensitization. The pain of fibromyalgia (FM) is nociplastic, occurs in 10-30% of rheumatologic disease patients, and its presence can influence disease severity assessment.

1) Ascertain the prevalence of FM and Widespread Pain (WP) in the CorEvitas psoriatic arthritis (PsA) registry as assessed by the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) questionnaires. 2) Characterize the demographic and clinical factors associated with FM and WP. 3) Ascertain the association of FM and WP on the Clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score and other disease activity measures.

PsA registry patients completing the WPI/SSS questionnaires since May 2020, at their most recent visit recorded in the registry, were analyzed.

The analysis included 1823 PsA patients; 11.1% fulfilled FM definition and 20.6% fulfilled WP definition. Several factors were associated with FM definition including female sex, depression/anxiety, impaired function, increased body mass index (BMI), and increased number of comorbidities. cDAPSA, patient pain and global, and tender joint count were twice as severe in patients with FM compared to those without.

Fibromyalgia prevalence is elevated in PsA and is associated with elevated disease measures, confounding reliable disease assessment for treat-to-target goals. Identification of fibromyalgia as an influential contextual factor in disease assessment is recommended.

Identifying the association between serum urate levels and gout flares in patients taking urate-lowering therapy: a post hoc cohort analysis of the CARES trial with consideration of dropout.

Annals of the Rheumatic Diseases

To investigate gout flare rates based on repeated serum urate (SU) measurements in a randomised controlled trial of urate-lowering therapy (ULT), accounting for dropout and death.

We performed a secondary analysis using data from Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout, which randomised participants to febuxostat or allopurinol, titrated to target SU <6 mg/dL with flare prophylaxis for 6 months. SU was categorised as ≤3.9, 4.0-5.9, 6.0-7.9, 8.0-9.9 or ≥ 10 mg/dL at each 3-6 month follow-up. The primary outcome was gout flare. Poisson regression models, adjusted for covariates and factors related to participant retention versus dropout, estimated gout flare incidence rate ratios by time-varying SU category.

Among 6183 participants, the median age was 65 years and 84% were male. Peak gout flare rates for all SU categories were observed in months 0-6, coinciding with the initiation of ULT and months 6-12 after stopping prophylaxis. Flare rates were similar across SU groups in the initial year of ULT. During months 36-72, a dose-response relationship was observed between the SU category and flare rate. Lower flare rates were observed when SU ≤3.9 mg/dL and greater rates when SU ≥10 mg/dL, compared with SU 4.0-5.9 mg/dL (p for trend <0.01).

Gout flare rates were persistently higher when SU ≥6 mg/dL after the first year of ULT after accounting for censoring. The spike in flares in all categories after stopping prophylaxis suggests a longer duration of prophylaxis may be warranted.

Adjustment of p values for multiple hypotheses: why, when and how.

Annals of the Rheumatic Diseases

It is quite common to investigate multiple hypotheses in a single study. For example, a researcher may want to investigate the effect on several ou...

NAT10 promotes synovial aggression by increasing the stability and translation of N4-acetylated PTX3 mRNA in rheumatoid arthritis.

Annals of the Rheumatic Diseases

Recent studies indicate that N-acetyltransferase 10 (NAT10)-mediated ac4C modification plays unique roles in tumour metastasis and immune infiltration. This study aimed to uncover the role of NAT10-mediated ac4C in fibroblast-like synoviocytes (FLSs) functions and synovial immune cell infiltration in rheumatoid arthritis (RA).

FLSs were obtained from active established patients with RA. Protein expression was determined by western blotting or immunohistochemistry or multiplexed immunohistochemistry. Cell migration was measured using a Boyden chamber. ac4C-RIP-seq combined with RNA-seq was performed to identify potential targets of NAT10. RNA immunoprecipitation was used to validate the interaction between protein and mRNA. NAT10 haploinsufficiency, inhibitor remodelin or intra-articular Adv-NAT10 was used to suppress arthritis in mice with delayed-type hypersensitivity arthritis (DYHA) and collagen II-induced arthritis (CIA) and rats with CIA.

We found elevated levels of NAT10 and ac4C in FLSs and synovium from patients with RA. NAT10 knockdown or specific inhibitor treatment reduced the migration and invasion of RA FLSs. Increased NAT10 level in the synovium was positively correlated with synovial infiltration of multiple types of immune cells. NAT10 inhibition in vivo attenuated the severity of arthritis in mice with CIA and DTHA, and rats with CIA. Mechanistically, we explored that NAT10 regulated RA FLS functions by promoting stability and translation efficiency of N4-acetylated PTX3 mRNA. PTX3 also regulated RA FLS aggression and is associated with synovial immune cell infiltration.

Our findings uncover the important roles of NAT10-mediated ac4C modification in promoting rheumatoid synovial aggression and inflammation, indicating that NAT10 may be a potential target for the treatment of RA, even other dysregulated FLSs-associated disorders.

Real-World Effectiveness of Pegloticase Associated with Use of Concomitant Immunomodulatory Therapy.

Arthritis Care Res

The objective was to ascertain pegloticase persistence and adverse events associated with concomitant immunomodulatory drug use in patients with gout.

We conducted a retrospective analysis of gout patients using the ACR's Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 through 6/2020. The first pegloticase infusion defined the index date. Based on concomitant immunomodulatory drug use, we identified 3 exposure groups: 1) Immunomodulatory drug initiators - patients initiating an immunomodulatory prescription ±60 days from index date; 2) Immunomodulatory drug prevalent users - patients receiving their first immunomodulatory drug prescription >60 days before the index date with at least one prescription within ±60 days of index date; and 3) Immunomodulatory non-users - patients receiving pegloticase without concomitant IMM drugs. We calculated the proportion of patients achieving a serum urate (SU) ≤6mg/dL and with lab abnormalities (WBC <3.4; platelets <135,000; HCT <30; ALT or AST ≥1.5X ULN) within 180 days after the index date. Cox regression analyzed time to pegloticase discontinuation controlling for potential confounders.

We identified 700 pegloticase users (91 immunomodulatory drug initiators, 33 immunomodulatory drug prevalent users, and 576 non-users) with median follow-up of 14 months. Immunomodulatory drug users were less likely to discontinue pegloticase. The adjusted hazard ratio of pegloticase discontinuation associated with concomitant immunomodulatory drug initiation was 0.52 (95% CI: 0.37,0.75) and 0.69 (95% CI: 0.42,1.16) for prevalent users. Lab abnormalities were uncommon (<5%) and were not higher with concomitant immunomodulatory use.

Consistent with clinical trials, results from this large observational registry suggest that concomitant immunomodulatory drug use improves pegloticase persistence.

Use of implementation strategies to promote the uptake of knee osteoarthritis practice guidelines and improve patient outcomes: A Systematic Review.

Arthritis Care Res

Translation of knee osteoarthritis (KOA) clinical practice guidelines (CPGs) to practice remains suboptimal. The primary purpose of this systematic review was to describe the use of implementation strategies to promote KOA CPG recommended care.

MEDLINE (via PubMed), Embase, CINAHL, and Web of Science were searched from inception to February 23, 2023, and subsequently updated and expanded on January 16, 2024. Implementation strategies were mapped per the Expert Recommendations for Implementing Change taxonomy. Risk of bias (RoB) was assessed using the Cochrane Effective Practice and Organization of Care criteria. The review was registered prospectively (CRD42023402383).

Nineteen studies were included in the final review. All (100% (n=4) studies that included the domains of provide interactive assistance, train and educate stakeholders (89%(n=18)), engage consumers (87%(n=15)) and support clinicians (79%(n=14)) reported change to provider adherence. Studies that reported a change to disability included train and educate stakeholders, engage consumers and adapt and tailor to context. Studies that used train and educate stakeholders, engage consumers, and support clinicians reported a change in pain and quality of life. Most studies had a low to moderate RoB.

Implementation strategies have the potential to impact clinician uptake of CPG's and patient reported outcomes (PROs). The implementation context, using an active learning strategy with a patient partner, restructuring funding models, and integrating taxonomies to tailor multifaceted strategies should be prioritized. Further experimental research is recommended to determine which implementation strategies are most effective.

Rethinking antiphospholipid syndrome to guide future management and research.

Nature Reviews Rheumatology

Antiphospholipid syndrome (APS) consists of thrombotic, non-thrombotic and obstetric clinical manifestations developing in individuals with persist...

Systematic literature review to inform the EULAR recommendations for the use of imaging in crystal-induced arthropathies in clinical practice.

Annals of the Rheumatic Diseases

To summarise current data regarding the use of imaging in crystal-induced arthropathies (CiAs) informing a European Alliance of Associations for Rheumatology task force.

We performed four systematic searches in Embase, Medline and Central on imaging for diagnosis, monitoring, prediction of disease severity/treatment response, guiding procedures and patient education in gout, calcium pyrophosphate dihydrate deposition (CPPD) and basic calcium phosphate deposition (BCPD). Records were screened, manuscripts reviewed and data of the included studies extracted. The risk of bias was assessed by validated instruments.

For gout, 88 studies were included. Diagnostic studies reported good to excellent sensitivity and specificity of dual-energy CT (DECT) and ultrasound (US), high specificity and lower sensitivity for conventional radiographs (CR) and CT. Longitudinal studies demonstrated sensitivity to change with regard to crystal deposition by US and DECT and inflammation by US and structural progression by CR and CT. For CPPD, 50 studies were included. Diagnostic studies on CR and US showed high specificity and variable sensitivity. There was a single study on monitoring, while nine assessed the prediction in CPPD. For BCPD, 56 studies were included. There were two diagnostic studies, while monitoring by CR and US was assessed in 43 studies, showing a reduction in crystal deposition. A total of 12 studies with inconsistent results assessed the prediction of treatment response. The search on patient education retrieved two studies, suggesting a potential role of DECT.

This SLR confirmed a relevant and increasing role of imaging in the field of CiAs.

Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology.

Annals of the Rheumatic Diseases

Sjögren disease (SjD) diagnosis often requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of patients with SjD lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD.

IgG binding to a high-density whole human peptidome array was quantified using sera from SSA- SjD cases and matched non-autoimmune controls. We identified the highest bound peptides using empirical Bayesian statistical filters, which we confirmed in an independent cohort comprising SSA- SjD (n=76), sicca-controls without autoimmunity (n=75) and autoimmune-feature controls (SjD features but not meeting SjD criteria; n=41). In this external validation, we used non-parametric methods for binding abundance and controlled false discovery rate in group comparisons. For predictive modelling, we used logistic regression, model selection methods and cross-validation to identify clinical and peptide variables that predict SSA- SjD and FS positivity.

IgG against a peptide from D-aminoacyl-tRNA deacylase (DTD2) bound more in SSA- SjD than sicca-controls (p=0.004) and combined controls (sicca-controls and autoimmune-feature controls combined; p=0.003). IgG against peptides from retroelement silencing factor-1 and DTD2 were bound more in FS-positive than FS-negative participants (p=0.010; p=0.012). A predictive model incorporating clinical variables showed good discrimination between SjD versus control (area under the curve (AUC) 74%) and between FS-positive versus FS-negative (AUC 72%).

We present novel autoantibodies in SSA- SjD that have good predictive value for SSA- SjD and FS positivity.