Improving the arthritis component of the SLEDAI-2K.

Objective: To propose a new definition for SLEDAI arthritis informed by imaging.

Methods: We performed a planned secondary analysis of observational data from a multicentre study evaluating SLE patients with inflammatory joint pain (swelling not required) using various clinical instruments, laboratory tests and ultrasound. For SLEDAI arthritis, assessors (blinded to ultrasound) were asked which of the glossary terms for arthritis in any version of the SLEDAI drove their decision to score for arthritis.

A multivariable prediction model to identify anti-CCP positive people in those with non-specific musculoskeletal symptoms in primary care.

Objectives: We aimed to develop a prediction model identifying people presenting to primary care with musculoskeletal symptoms likely to be anti-CCP positive and therefore at risk of developing rheumatoid arthritis (RA).

Methods: Participants aged ≥16 years, with new-onset non-specific musculoskeletal symptoms and no history of clinical synovitis, completed a symptom questionnaire and had an anti-CCP test. Model development used LASSO-penalised logistic regression, performance was assessed using area under the receiver operating characteristic curve (AUROC) and decision curve analysis, model over-fit was estimated using bootstrapping and cross-validation.

Rheumatoid arthritis: a review of the key clinical features and ongoing challenges of the disease.

Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that primarily affects the joints and periarticular soft tissue. The development of joint swelling is traditionally regarded as the starting point of the disease. Emerging evidence indicates that RA patients often experience a preclinical stage characterized by immunological and inflammatory changes before developing the disease.

Efficacy and safety of filgotinib in patients with rheumatoid arthritis: week 156 interim results from a long-term extension study.

Background: Janus kinase inhibitors are an effective option for achieving sustained remission or low disease activity in patients with rheumatoid arthritis (RA) following inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. Filgotinib is a Janus kinase 1-preferential inhibitor available in two doses for moderate-to-severe RA. We report the long-term efficacy and safety of filgotinib.

Crosstalk between the circatidal and circadian clocks mediates behavioral adaptation to tidal patterns.

The ability to anticipate tides is critical for a wide range of marine organisms, but this task is complicated by the diversity of tidal patterns on Earth. Previous findings suggest that organisms whose geographic range spans multiple types of tidal cycles can produce distinct patterns of rhythmic behavior that correspond to the tidal cycles they experience. How this behavioral plasticity is achieved, however, is unclear.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

Biomarkers in the diagnosis, prognosis and management of rheumatoid arthritis: A comprehensive review.

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune condition that primarily affects the joints and periarticular soft tissues. In the past two decades, the discovery of new biomarkers has contributed to advances in the understanding of the pathogenesis and natural history of RA. These biomarkers, including genetic, clinical, serological and imaging biomarkers, play a key role in the different stages and aspects of RA, from the so called 'pre-clinical RA', which is characterized by subclinical pathological events, such as autoimmunity and inflammation, to diagnosis (including differential diagnosis), treatment decision making and disease monitoring.

PERI-operative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations (the PERISCOPE trial) - a study protocol for a pragmatic, UK multicentre, superiority randomised controlled trial with an internal pilot, economic evaluation and nested qualitative study.

Introduction: Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently, bDMARDs are withheld during the perioperative period due to potential infection risk.

Fly into tranquility: GABA's role in Drosophila sleep.

Sleep is conserved across the animal kingdom, and Drosophila melanogaster is a prime model to understand its intricate circadian and homeostatic control. GABA (gamma-aminobutyric acid), the brain's main inhibitory neurotransmitter, plays a central role in sleep. This review delves into GABA's complex mechanisms of actions within Drosophila's sleep-regulating neural networks.

Design of ANCHOR-RA: a multi-national cross-sectional study on screening for interstitial lung disease in patients with rheumatoid arthritis.

Background: Patients with rheumatoid arthritis (RA) are at risk of developing interstitial lung disease (ILD), which is associated with high mortality. Screening tools based on risk factors are needed to decide which patients with RA should be screened for ILD using high-resolution computed tomography (HRCT). The ANCHOR-RA study is a multi-national cross-sectional study that will develop a multivariable model for prediction of RA-ILD, which can be used to inform screening for RA-ILD in clinical practice.

Cnidarians are CLOCKing in.

Studies of the starlet sea anemone provide important insights into the early evolution of the circadian clock in animals.

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test.

Objectives: To investigate the role of third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in predicting progression to inflammatory arthritis (IA) in individuals with new musculoskeletal (MSK) symptoms and a negative second-generation anti-CCP antibody test (anti-CCP2-).

Methods: 469 anti-CCP2- individuals underwent baseline anti-CCP3 testing (QUANTA Lite CCP3; Inova Diagnostics) and received a post enrolment 12-month questionnaire. A rheumatologist confirmed or excluded diagnosis of IA.

Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy.

Objective: The tapering of biologic disease-modifying antirheumatic drug (b-DMARD) therapy for patients with rheumatoid arthritis (RA) in stable remission is frequently undertaken, but specific guidance on how to successfully taper is lacking. The objective of this study is to identify predictors of flare in patients in stable b-DMARD-induced clinical remission, who did or did not follow structured b-DMARD tapering.

Methods: Patients with RA receiving b-DMARD treatment who had achieved sustained remission according to a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) <2.

Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial.

Background: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept.

Methods: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands.

Clocks at sea: the genome-editing tide is rising.

The coastline is a particularly challenging environment for its inhabitants. Not only do they have to cope with the solar day and the passing of seasons, but they must also deal with tides. In addition, many marine species track the phase of the moon, especially to coordinate reproduction.

Elevated Serum Levels of Zonulin Family Peptides in Anticitrullinated Protein Antibody-Positive At-Risk Individuals Without Arthritis.

Objective: Recent advances imply that early events triggering rheumatoid arthritis (RA) occur at mucosal surfaces. We aimed to evaluate whether intestinal permeability is altered in patients at increased risk of RA, and/or predicts the development of clinical arthritis, by measuring serum zonulin family peptides (ZFP) levels, which are shown to reflect intestinal barrier integrity.

Methods: Two independent prospective observational cohorts were studied, including subjects with musculoskeletal symptoms and anticitrullinated protein antibodies (ACPA), but without clinical arthritis at baseline.

Factors associated with resolution of ultrasound subclinical synovitis in anti-CCP-positive individuals with musculoskeletal symptoms: a UK prospective cohort study.

Background: Subclinical synovitis occurs in a third of individuals at risk of rheumatoid arthritis. The objective of this study was to assess the reversibility of subclinical synovitis in individuals at risk of rheumatoid arthritis who are positive for anti-cyclic citrullinated peptide (CCP) antibody with musculoskeletal symptoms and investigate factors associated with its resolution within 12 months.

Methods: We conducted a single-centre, prospective, cohort study in the UK, recruiting individuals aged 18 years or older who were anti-CCP-positive with a new non-specific musculoskeletal symptom but no clinical synovitis.

Rheumatoid arthritis.

Rheumatoid arthritis is a chronic, systemic, autoimmune inflammatory disease that mainly affects the joints and periarticular soft tissues. In this Seminar, we provide an overview of the main aspects of rheumatoid arthritis. Epidemiology and advances in the understanding of rheumatoid arthritis pathogenesis will be reviewed.

ATXN2 is a target of N-terminal proteolysis.

Spinocerebellar ataxia 2 (SCA2) is a neurodegenerative disorder caused by the expansion of the poly-glutamine (polyQ) tract of Ataxin-2 (ATXN2). Other polyQ-containing proteins such as ATXN7 and huntingtin are associated with the development of neurodegenerative diseases when their N-terminal polyQ domains are expanded. Furthermore, they undergo proteolytic processing events that produce N-terminal fragments that include the polyQ stretch, which are implicated in pathogenesis.

Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) and Sjögren Tool for Assessing Response (STAR) to B Cell-Targeted Therapy in the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS).

Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints.

Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing.

Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG.

Poly-Refractory Rheumatoid Arthritis: An Uncommon Subset of Difficult to Treat Disease With Distinct Inflammatory and Noninflammatory Phenotypes.

Objective: To investigate the prevalence of poly-refractory rheumatoid arthritis (RA) defined as failure of all biological (b)/targeted synthetic (ts)-disease-modifying drugs (DMARDs). To further investigate whether patients with persistent inflammatory refractory RA (PIRRA) and noninflammatory refractory RA (NIRRA), determined by objective ultrasound (US) synovitis, have distinct clinical phenotypes in both EULAR difficult-to-treat RA (D2T-RA) and poly-refractory RA groups.

Methods: A cross-sectional study of 1,591 patients with RA on b/tsDMARDs that evaluated D2T-RA criteria and subclassified as poly-refractory if inefficacy/toxicity to at least one drug of all classes.