The course of cytokine and chemokine gene expression in clinically suspect arthralgia patients during progression to inflammatory arthritis.

Objectives: Autoantibody responses increase years before the onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and chemokine levels also increase years before IA onset. However, the course in the at-risk stage of CSA during progression to disease or non-progression is unknown.

The Role of Genetics in Clinically Suspect Arthralgia and Rheumatoid Arthritis Development: A Large Cross-Sectional Study.

Objective: To investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients.

Methods: Using analyses of variance, chi-square tests, and mean risk difference analyses, we investigated the association of an RA polygenic risk score (PRS) and HLA shared epitope (HLA-SE) with all participant groups, both unstratified and stratified for anti-citrullinated protein antibody (ACPA) status. We used 3 separate data sets sampled from the same Dutch population (1,015 healthy controls, 479 CSA patients, and 1,146 early classified RA patients).

Towards a simplified fluid-sensitive MRI protocol in small joints of the hand in early arthritis patients: reliability between modified Dixon and regular Gadolinium enhanced TSE fat saturated MRI-sequences.

Objective: MRI of small joints plays an important role in the early detection and early treatment of rheumatoid arthritis. Despite its sensitivity to demonstrate inflammation, clinical use is hampered by accessibility, long scan time, intravenous contrast, and consequent high costs. To improve the feasibility of MRI implementation in clinical practice, we introduce a modified Dixon sequence, which does not require contrast and reduces total acquisition time to 6 min.

Investigating Tissue-Specific Abnormalities in Alzheimer's Disease with Multi-Shell Diffusion MRI.

Background: Most studies using diffusion-weighted MRI (DW-MRI) in Alzheimer's disease (AD) have focused their analyses on white matter (WM) microstructural changes using the diffusion (kurtosis) tensor model. Although recent works have addressed some limitations of the tensor model, such as the representation of crossing fibers and partial volume effects with cerebrospinal fluid (CSF), the focus remains in modeling and analyzing the WM.

Objective: In this work, we present a brain analysis approach for DW-MRI that disentangles multiple tissue compartments as well as micro- and macroscopic effects to investigate differences between groups of subjects in the AD continuum and controls.

Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial.

Background: Rheumatoid arthritis is the most common autoimmune disease worldwide and requires long-term treatment to suppress inflammation. Currently, treatment is started when arthritis is clinically apparent. We aimed to evaluate whether earlier intervention, in the preceding phase of arthralgia and subclinical joint inflammation, could prevent the development of clinical arthritis or reduce the disease burden.

Associating Alzheimer's disease pathology with its cerebrospinal fluid biomarkers.

Alzheimer's disease CSF biomarkers 42 amino acid long amyloid-β peptide (Aβ1-42), total tau protein (T-tau), and tau protein phosphorylated at threonine 181 (P-tau181) are considered surrogate biomarkers of Alzheimer's disease pathology, and significantly improve diagnostic accuracy. Their ability to reflect neuropathological changes later in the disease course is not well characterized. This study aimed to assess the potential of CSF biomarkers measured in mid to late stage Alzheimer's disease to reflect post-mortem neuropathological changes.

Central Role of Semaphorin 3B in a Serum-Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis.

Objective: Semaphorin 3B (Sema3B) decreases the migratory and invasive capacities of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and suppresses expression of matrix metalloproteinases. We undertook this study to examine the role of Sema3B in a mouse model of arthritis and its expression in RA patients.

Methods: Clinical responses, histologic features, and FLS function were examined in wild-type (WT) and Sema3B mice in a K/BxN serum transfer model of arthritis.

Diagnostic Performance of Automated MRI Volumetry by icobrain dm for Alzheimer's Disease in a Clinical Setting: A REMEMBER Study.

Background: Magnetic resonance imaging (MRI) has become important in the diagnostic work-up of neurodegenerative diseases. icobrain dm, a CE-labeled and FDA-cleared automated brain volumetry software, has shown potential in differentiating cognitively healthy controls (HC) from Alzheimer's disease (AD) dementia (ADD) patients in selected research cohorts.

Objective: This study examines the diagnostic value of icobrain dm for AD in routine clinical practice, including a comparison to the widely used FreeSurfer software, and investigates if combined brain volumes contribute to establish an AD diagnosis.

MRI-detected synovitis of the small joints predicts rheumatoid arthritis development in large joint undifferentiated inflammatory arthritis.

Objectives: New onset undifferentiated large joint inflammatory arthritis can be diagnostically challenging. It is unknown how often these patients progress to RA, and how they can be identified at first presentation. We assessed clinical and serological features associated with RA development in patients with an undifferentiated mono- or oligo-articular large joint arthritis, and with keen interest in whether an MRI of the small joints of the hand and foot would aid diagnosis.

Prediction of the Progression of Undifferentiated Arthritis to Rheumatoid Arthritis Using DNA Methylation Profiling.

Objective: The term "undifferentiated arthritis (UA)" is used to refer to all cases of arthritis that do not fit a specific diagnosis. A significant percentage of UA patients progress to rheumatoid arthritis (RA), others to a different definite rheumatic disease, and the rest undergo spontaneous remission. Therapeutic intervention in patients with UA can delay or halt disease progression and its long-term consequences.

Intermetatarsal Bursitis, a Novel Feature of Juxtaarticular Inflammation in Early Rheumatoid Arthritis Related to Clinical Signs: Results of a Longitudinal Magnetic Resonance Imaging Study.

Objective: Intermetatarsal bursae in the forefeet possess a synovial lining similar to joints and tendon sheaths. Inflammation of these bursae (intermetatarsal bursitis [IMB]) was recently identified as specific for early rheumatoid arthritis (RA). The present study was undertaken to determine if IMB is indeed an RA feature by assessing the following: 1) the association with other local inflammatory measures (synovitis, tenosynovitis, and osteitis), 2) the association with clinical signs, and 3) whether it responds to disease-modifying antirheumatic drug (DMARD) therapy similarly to other local inflammatory measures.

Tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA: a large cross-sectional MRI study.

Objectives: Clinically evident tenosynovitis can be seen in established rheumatoid arthritis (RA). Imaging research has recently shown that tenosynovitis at small joints occurs in early RA, contributes to typical RA symptoms (including joint swelling) and is infrequent in healthy controls. Imaging-detectable tenosynovitis is often not recognisable at joint examination, hence its prevalence can therefore be underestimated.

The value of inquiring about functional impairments for early identification of inflammatory arthritis: a large cross-sectional derivation and validation study from the Netherlands.

Objectives: Healthcare professionals other than rheumatologists experience difficulties in detecting early inflammatory arthritis (IA) by joint examination. Self-reported symptoms are increasingly considered as helpful and could be incorporated in online tools to assist healthcare professionals, but first their discriminative ability must be assessed. As part of this effort, we evaluated whether inquiring about functional impairments could aid early IA identification.

Increased frequency of intermetatarsal and submetatarsal bursitis in early rheumatoid arthritis: a large case-controlled MRI study.

Background: The forefoot is a preferential location for joint and tendon sheath inflammation in rheumatoid arthritis (RA). It also contains bursae, of which the intermetatarsal bursae have a synovial lining. Some small imaging studies suggested that intermetatarsal bursitis (IMB) and submetatarsal bursitis (SMB) are involved in RA, but their association has not been thoroughly explored.

Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort.

Background: Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients who do or do not develop clinically evident inflammatory arthritis (IA).

Methods: Two hundred thirty-six consecutive patients presenting with arthralgia clinically suspected for progression to RA were followed until IA development or else for median 24 months (IQR 12-26).

Differing time-orders of inflammation decrease between ACPA subsets in RA patients suggest differences in underlying inflammatory pathways.

Objectives: Advanced imaging modalities have shown that not only joints but also bones and tendon sheaths can be inflamed at diagnosis of RA. We aimed to better understand the time-order in which the inflamed tissues respond to DMARD treatment. Also, because ACPA status may reflect a different pathophysiology, differences in time-order of inflammation decrease were hypothesized between these disease types.

TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis (TREAT EARLIER): a randomized, double-blind, placebo-controlled clinical trial protocol.

Background: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs.

Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: A longitudinal cohort study in the Netherlands.

Background: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients.

Referring early arthritis patients within 6 weeks versus 12 weeks after symptom onset: an observational cohort study.

Background: The first recommendation of the European League Against Rheumatism for the management of early arthritis states that patients should be referred to, and seen by, a rheumatologist within 6 weeks after symptom onset. However, implementation of this recommendation is a challenge, and evidence supporting this timeframe compared with longer timeframes is absent. Therefore, we aimed to investigate whether visiting a rheumatologist within 6 weeks of symptom onset relates to improved long-term outcomes compared with visiting a rheumatologist between 7 and 12 weeks after symptom onset.