Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

Changes in Youth Mental Health Following a School Lockdown due to Violent and Firearm-Related Threats.

Background: School shooting events and lockdowns have increased in the United States, raising concerns about their impact on youth mental health.

Method: This study assessed the association between school lockdowns and changes in youth mental health in 10,049 children who participated in the Adolescent Brain and Cognitive Development study. The exposure was school lockdowns related to violence and shooting incidents, and the outcomes were Child Behavior Checklist scores on five mental health disorders.

Vitrification and rapid rewarming of precision-cut liver slices for pharmacological and biomedical research.

Background And Aims: High-throughput in vitro pharmacological toxicity testing is essential for drug discovery. Precision-cut liver slices (PCLS) provide a robust system for screening that is more representative of the complex 3D structure of the whole liver than isolated hepatocytes. However, PCLS are not available as off-the-shelf products, significantly limiting their translational potential.

Are ultrasound salivary parenchymal lesions more severe in primary Sjögren patients with a longer disease duration? A cross-sectional study.

Objectives: Salivary gland ultrasound (SGUS) has an interest in primary Sjögren's disease (pSD) for diagnosis, but the evolution of parenchymal lesions over time is unknown. The objective of this study was to assess the severity of ultrasound abnormalities in relation to pSD duration from the time of buccal dryness onset.

Methods: In this cross-sectional international multicentre study, patients with pSD according to the 2002 or 2016 ACR/EULAR classification criteria were included.

The effect of smoking on Sjögren's disease development and severity: a comprehensive literature review.

Unlike other autoimmune diseases, little is known about the environmental risk factors for Sjögren's disease (SjD). Smoking is an important risk factor for rheumatoid arthritis but the relationship between smoking and SjD is more complex to understand. Current smoking seems to be negatively linked to SjD, whereas there is mixed data on past smoking.

Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study.

Objective: The objective of this study was to report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).

Methods: Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period [TP]1). At week 24, patients on 300 mg were rerandomized to continue 300 mg or receive placebo until week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, and patients on 5 and 50 mg directly entered posttreatment safety follow-up.

Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjögren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study.

Background: Sjögren's disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sjögren's disease.

Methods: This randomised, double-blind, placebo-controlled, phase 2b study, conducted at 71 sites in 23 countries, enrolled patients aged 18 years or older fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) 2016 criteria.

Tailoring the treatment of inflammatory rheumatic diseases by a better stratification and characterization of the clinical patient heterogeneity. Findings from a systematic literature review and experts' consensus.

Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders.

Granulocyte-macrophage colony-stimulating factor neutralisation in patients with axial spondyloarthritis in the UK (NAMASTE): a randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis.

British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease.

Sjögren disease (SD) is a chronic, autoimmune disease of unknown aetiology with significant impact on quality of life. Although dryness (sicca) of the eyes and mouth are the classically described features, dryness of other mucosal surfaces and systemic manifestations are common. The key management aim should be to empower the individual to manage their condition-conserving, replacing and stimulating secretions; and preventing damage and suppressing systemic disease activity.

Concomitant Sjögren's disease as a biomarker for treatment effectiveness in rheumatoid arthritis - results from the Swiss clinical quality management cohort.

Objective: To investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren's disease (SjD).

Methods: In this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD.

Reliability Exercise of Ultrasound Salivary Glands in Sjögren's Disease: An International Web Training Initiative.

Introduction: Major salivary gland ultrasonography (SGUS) demonstrated its good metric properties as an outcome measure for diagnosing primary Sjögren's disease (SD). The objective was to assess SGUS reliability among sonographers with different levels of experience, using web training.

Methods: Sonographers from expert centers participated in the reliability exercise.

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.

The impact of concomitant Sjögren's disease on rheumatoid arthritis disease activity: a systematic review and meta-analysis.

Objectives: Rheumatoid arthritis (RA) and Sjögren's syndrome (SS) frequently co-exist but the consequence for RA disease activity of having concomitant SS (RA/SS) is not well established. We conducted a systematic review and meta-analysis to investigate the impact of SS on disease outcomes in individuals with RA.

Methods: We searched Web of Science (Core Collection, FSTA, Medline), PubMed and Cochrane databases, without language restriction.

Fifteen-minute consultation: Management of albuminuria in children and young people with diabetes.

Albuminuria is a marker of diabetic kidney disease. Raised albuminuria in children and young people with diabetes is associated with an increased risk of microvascular and macrovascular complications. This review provides guidance for paediatricians caring for children and young people with type 1 and type 2 diabetes on screening, investigations and treatments for albuminuria in line with relevant national and international recommendations.

School-based law enforcement strategies to reduce crime, increase perceptions of safety, and improve learning outcomes in primary and secondary schools: A systematic review.

Background: School-based law enforcement (SBLE) has become a common intervention. Although SBLE is meant to make schools safer, critics suggest it may not accomplish this purpose, and may have unintended negative consequences such as increasing students' exclusionary discipline or contact with the criminal justice system. There may also be secondary effects related to perceptions of the school or student learning.

Statement on the effects of law enforcement in school settings.

School-based law enforcement (SBLE) have become increasingly common in U.S. schools over recent decades despite the controversy surrounding their presence and lack of consensus around their associated benefits and harms.

Alternative ground covers and strip-tilling in CBD hemp production.

Objective: Little research has been done on managing soil health for large-scale, outdoor hemp production, contributing to the possible overuse of black plastic for weed suppression. Our experiment aimed to understand the performance of alternative ground covers including forage crops and hay as well as a less disruptive tilling method called strip-tilling compared to black plastic.

Results: Yield and soil health data were taken from three experimental plantings from two different outdoor CBD hemp farms in Vermont, USA.

Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome: proteomic and network analysis.

Objectives: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes.