MUC5B Promoter Variant and Survival in Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Objective: Investigate the association between the MUC5B rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD).

Methods: We studied participants in the Veteran Affairs Rheumatoid Arthritis (VARA) registry with validated ILD diagnoses. Participants were followed until death or end of study period.

A study of implementation factors for a novel approach to clinical trials: constructs for consideration in the coordination of direct-to-patient online-based medical research.

Background: Traditional medical research infrastructures relying on the Centers of Excellence (CoE) model (an infrastructure or shared facility providing high standards of research excellence and resources to advance scientific knowledge) are often limited by geographic reach regarding patient accessibility, presenting challenges for study recruitment and accrual. Thus, the development of novel, patient-centered (PC) strategies (e.g.

Signal Regulatory Protein α Expression in Systemic Vasculitis.

Objective: Signal regulatory protein α (SIRPα) is found primarily on myeloid cells, including macrophages and neutrophils; binds to CD47; and regulates phagocytosis, antigen presentation, cellular fusion, cell proliferation, and migration. Therefore, SIRPα may be involved in the pathogenesis of autoimmune diseases, including systemic vasculitis. This study aimed to assess SIRPα expression in tissue samples from patients with vasculitis.

Assessment of Damage in Takayasu's Arteritis.

Objectives: To evaluate damage and clinical characteristics associated with damage in Takayasu's arteritis (TAK).

Methods: Patients with TAK enrolled in a multicentre, prospective, observational study underwent standardized damage assessment every 6 months using the Vasculitis Damage Index (VDI) and the Large-Vessel Vasculitis Index of Damage (LVVID).

Results: The study included 236 patients with TAK: 92% female, 81% Caucasian; median (25th, 75th percentile) disease duration = 2.

The association of TNF inhibitor use with incident cardiovascular events in radiographic axial spondyloarthritis.

Background: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA.

Methods: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes.

Antibodies to Malondialdehyde-Acetaldehyde Adduct Are Associated With Prevalent and Incident Rheumatoid Arthritis-Associated Interstitial Lung Disease in US Veterans.

Objective: The objective of this study is to determine the associations of protein-specific anti-malondialdehyde-acetaldehyde (MAA) antibodies with prevalent and incident rheumatoid arthritis-interstitial lung disease (RA-ILD).

Methods: Within a multicenter, prospective cohort of US veterans with RA, RA-ILD was validated by medical record review of clinical diagnoses, chest imaging, and pathology. Serum antibodies to MAA-albumin, MAA-collagen, MAA-fibrinogen, and MAA-vimentin (IgA, IgM, and IgG) were measured by a standardized enzyme-linked immunosorbent assay.

Underuse of Antiviral Drugs to Prevent Progression to Severe COVID-19 - Veterans Health Administration, March-September 2022.

Antiviral drugs reduce the rate of progression to severe COVID-19 when given to patients with mild-to-moderate disease within 5 days of symptom onset. Despite being recommended for patients at high risk for progression to severe COVID-19 because of age or chronic conditions, reported antiviral use among the general adult population has been ≤35%. To ascertain reasons for underuse of antiviral medications to prevent severe COVID-19 and propose interventions accordingly, a detailed review was conducted of 110 Veterans Health Administration patients with mild-to-moderate infection at high risk for progression because of underlying conditions (organ transplantation or hematologic malignancies) who did not receive an antiviral drug.

Plasma Matrix Metalloproteinase Concentrations and Risk of Interstitial Lung Disease in a Prospective Rheumatoid Arthritis Cohort.

Objective: To evaluate the associations of plasma matrix metalloproteinases (MMPs) with prevalent and incident interstitial lung disease (ILD) in people with rheumatoid arthritis (RA).

Methods: Within a multicenter, prospective cohort of US veterans with RA, we performed a cross-sectional study of prevalent ILD and cohort study of incident ILD. ILD diagnoses were validated by medical record review of provider diagnoses and chest imaging and/or pathology reports.

Development and Internal Validation of a Clinical and Genetic Risk Score for Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Objective: Although clinical and genetic risk factors have been identified for rheumatoid arthritis-associated interstitial lung disease (RA-ILD), there are no current tools allowing for risk stratification. We sought to develop and validate an ILD risk model in a large, multicentre, prospective RA cohort.

Methods: Participants in the Veterans Affairs RA (VARA) registry were genotyped for 12 single nucleotide polymorphisms (SNPs) associated with idiopathic pulmonary fibrosis.

Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Introduction: Although the alternative complement pathway has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV.

Methods: The complement fragment Ba was measured by enzyme-linked immunosorbent assay in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a nonrenal flare, and 20 in long-term remission.

Risk of severe coronavirus disease 2019 despite vaccination in patients requiring treatment with immune-suppressive drugs: A nationwide cohort study of US Veterans.

Background: Patients taking immune-suppressive drugs are at increased risk of severe coronavirus disease 2019 (COVID-19), not fully ameliorated by vaccination. We assessed the contributions of clinical and demographic factors to the risk of severe disease despite vaccination in patients taking immune-suppressive medications for solid organ transplantation (SOT), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis.

Methods: Veterans Health Administration electronic health records were used to identify patients diagnosed with RA, IBD, psoriasis, or SOT who had been vaccinated against severe acute respiratory syndrome coronavirus 2, were subsequently infected, and had received immune-suppressive drugs within 3 months before infection.

Mitochondrial-mediated inflammation and platelet activation in giant cell arteritis.

Markers of extracellular mitochondria are present in giant cell arteritis (GCA) patients. However, their role in promoting inflammation and platelet activation is no known. To investigate this, isolated mitochondria were opsonized with plasma from GCA patients or healthy individuals and incubated with peripheral blood mononuclear cells (PBMCs) or platelets and assessed for inflammatory cytokine production and platelet activation.

Complement.

The role of complement in human autoimmune, inflammatory, and infectious diseases is reviewed, focusing on clinical applicability. A typical case is presented in which serum testing for C3 and C4 is performed to help assess a syndrome with a broad differential diagnosis. The review includes a discussion of complement deficiency states, consumption of complement by diseases characterized by immune-complex formation and deposition, usefulness and interpretation of laboratory tests for complement, and development of drugs targeting specific components of the complement pathway for a growing number of indications.

The Association Between Age at Diagnosis and Disease Characteristics and Damage in Patients With ANCA-Associated Vasculitis.

Objective: This study examined the relationship between age at diagnosis and disease characteristics and damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Analysis of a prospective longitudinal cohort of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA) in the Vasculitis Clinical Research Consortium (2013-2021). Disease cohorts were divided by age at diagnosis (years): children (<18), young adults (18-40), middle-aged adults (41-65), and older adults (>65).

Maintaining the Utility of Coronavirus Disease 2019 Pandemic Severity Surveillance: Evaluation of Trends in Attributable Deaths and Development and Validation of a Measurement Tool.

Background: Death within a specified time window following a positive SARS-CoV-2 test is used by some agencies for attributing death to COVID-19. With Omicron variants, widespread immunity, and asymptomatic screening, there is cause to re-evaluate COVID-19 death attribution methods and develop tools to improve case ascertainment.

Methods: All patients who died following microbiologically confirmed SARS-CoV-2 in the Veterans Health Administration (VA) and at Tufts Medical Center (TMC) were identified.

The Future of Vasculitis: A Manifesto.

Predictions for a general path forward in vasculitis care and research are provided based on advances made in the past 20 years. Prospects for advances in translational research with potential to improve care are highlighted, including identification of hemato-inflammatory diseases, autoantigens, disease mechanisms in animal models, and biomarkers. A list of active randomized trials is provided, and areas of potential paradigm shifts in care are highlighted.

Improving COVID-19 Disease Severity Surveillance Measures: Statewide Implementation Experience.

Measurement of the burden of COVID-19 on U.S. hospitals has been an important element of the public health response to the pandemic.

Identifying shared genetic architecture between rheumatoid arthritis and other conditions: a phenome-wide association study with genetic risk scores.

Background: Rheumatoid arthritis (RA) shares genetic variants with other autoimmune conditions, but existing studies test the association between RA variants with a pre-defined set of phenotypes. The objective of this study was to perform a large-scale, systemic screen to determine phenotypes that share genetic architecture with RA to inform our understanding of shared pathways.

Methods: In the UK Biobank (UKB), we constructed RA genetic risk scores (GRS) incorporating human leukocyte antigen (HLA) and non-HLA risk alleles.