Highlights from the breakout session: transcriptomic approaches to the study of systemic vasculitis.

The search for targeted therapies and biomarkers for immune-mediated systemic vasculitis requires detailed understanding of molecular pathogenesis. Whilst candidate approaches have identified new opportunities for drug repurposing, they also miss novel approaches for targeting critical immunological or stromal pathways. On the other hand, bulk transcriptional profiling may fail to capture differences in cellular composition and, depending on the cell source profiled, miss important changes within inflamed vascular tissue.

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis.

Objectives: This project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk of CV-related traits.

Methods: 1946 GCA patients with clinicodemographic data at GCA presentation were included. Associations between pre-existing CV-related traits (including Polygenic Risk Scores (PRS) for CV traits) and cranial ischaemic complications were tested.

Identification of clonally expanded T-cell receptor sequences in giant cell arteritis.

Background: Arterial wall inflammation in giant cell arteritis (GCA) is characterized by T-cell infiltration and granuloma formation. There have been limited studies investigating the diversity of the T-cell receptor (TCR) repertoire in GCA patients. Here we aim to identify disease-relevant TCRs.

Commonly prescribed medications and risk of pneumonia and all-cause mortality in people with idiopathic pulmonary fibrosis: a UK population-based cohort study.

Background: A growing body of evidence suggests that prolonged use of inhaled corticosteroids (ICS) and proton pump inhibitors (PPIs) is associated with increased risks of pneumonia. A substantial proportion of people with idiopathic pulmonary fibrosis (IPF) are prescribed PPIs or ICS to treat common comorbidities, giving rise to concerns that use of these medications may be associated with potential harms in this patient population.

Methods: We used UK Clinical Practice Research Datalink (CPRD) Aurum primary care data linked to national mortality and hospital admissions data to create a cohort of people diagnosed with IPF on or after 1 January 2010.

Proteomic Profiling of the Large-Vessel Vasculitis Spectrum Identifying Shared Signatures of Innate Immune Activation and Stromal Remodeling.

Objective: Takayasu arteritis (TAK) and giant cell arteritis (GCA), the most common forms of large-vessel vasculitis (LVV), can result in serious morbidity. Understanding the molecular basis of LVV should aid in developing better biomarkers and treatments.

Methods: Plasma proteomic profiling of 184 proteins was performed in two cohorts.

Infliximab versus interferon-alpha in the treatment of Behçet's Syndrome: Clinical data from the BIO-BEHÇET'S randomised controlled trial.

Objectives: Whilst biologic therapy is used for Behçet's Syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence-and no predictive biomarkers to optimally inform choice. BIO-BEHÇET'S was a randomised, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet's.

Methods: Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres.

Plasma MERTK is causally associated with infection mortality.

Background: Infectious diseases are a major cause of mortality in spite of existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates of infection mortality and then apply Mendelian randomisation (MR) to yield biomarkers that may be causally associated.

Methods: We used UK Biobank plasma proteomic data to associate 2923 plasma proteins with infection mortality before 31st December 2019 (240 events in 52,520 participants).

Patient pathways for four major chronic respiratory diseases in England between 2008 and 2021.

Background: Not all chronic diseases have clear pathways and time targets for diagnosis. We explored pathways and timings for four major chronic respiratory diseases in England.

Methods: Using deidentified electronic healthcare records from Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, we derived cohorts of patients diagnosed with asthma, chronic obstructive pulmonary disease (COPD), ILD or bronchiectasis at three time periods (2008/2009, 2018/2019 and 2020/2021).

Spinal catheter revision in pediatric intrathecal baclofen pumps: risk factors and postoperative outcomes.

Objective: Intrathecal baclofen (ITB) pumps are commonly used in pediatric patients with cerebral palsy (CP) and medically refractory spasticity. However, catheter malfunction and associated risk factors are not well understood. The aim of this study was to examine potential risk factors for spinal catheter malfunction and characterize postoperative follow-up to understand the clinical consequences.

Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: Identification of metabolic correlates of fatigue.

Objective: In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA).

Methods: Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls.

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.

Background: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases.

Incidence, prevalence and mortality of idiopathic pulmonary fibrosis in England from 2008 to 2018: a cohort study.

Background: Owing to discrepancies in methodologies and how idiopathic pulmonary fibrosis (IPF) is diagnosed it is challenging to establish a consistent understanding of the disease burden In the UK, over 10 years ago, the incidence and prevalence of IPF were reported as 2.8-8.7 per 100 000 person-years (from 2000 to 2012) and 39 per 100 000 persons (in 2012), respectively.

Adenosine metabolic signature in circulating CD4+ T cells predicts remission in rheumatoid arthritis.

Objectives: Long-term outcomes in rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate (MTX) remains the first-line disease modifying therapy, however there are no biomarkers with which to identify those most likely to achieve remission. To address this unmet need we explored metabolic pathways involved in MTX mechanism of action within circulating CD4+T cells in a cohort of treatment naive patients with early RA.

Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT-SEQUOIA.

Background: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary.

Estimating overdiagnosis in giant cell arteritis diagnostic pathways using genetic data: genetic association study.

Objectives: GCA can be confirmed by temporal artery biopsy (TAB) but false negatives can occur. GCA may be overdiagnosed in TAB-negative cases, or if neither TAB nor imaging is done. We used HLA genetic association of TAB-positive GCA as an 'unbiased umpire' test to estimate historic overdiagnosis of GCA.

Common co-morbidities in polymyalgia rheumatica and giant cell arteritis: cross-sectional study in UK Biobank.

Objective: The aim was to determine prevalent co-morbidities in cases with PMR or GCA compared with matched controls.

Methods: This was a nested, cross-sectional case-control study within the UK Biobank, which recruited participants aged 40-69 years. Case status was defined as self-reported prior diagnosis of PMR or GCA.

Micro-RNA content of circulating extracellular vesicles in early rheumatoid arthritis as biomarkers and mediators of methotrexate efficacy.

Objectives: Extracellular vesicles (EVs) are abundant in body fluids, contributing to intercellular signalling by transferring cargo that includes microRNAs (miRs)-themselves implicated in pathobiology. For the first time we evaluated the potential of EV miRs to contribute diagnostic information in early RA, predict methotrexate (MTX) efficacy or shed light on the drug's mechanism of action.

Methods: Seven hundred and ninety-eight miRs isolated from serum-derived EVs of 46 patients with untreated RA, 23 with untreated polymyalgia rheumatica (PMR; inflammatory disease control group) and 12 in whom significant inflammatory disease had been excluded (non-inflammatory controls; NICs) were profiled (NanoString); the same measurements were made for RA patients after 6 months' MTX treatment.

Prevalence of Poorly Controlled Asthma and Factors Associated with Specialist Referral in Those with Poorly Controlled Asthma in a Paediatric Asthma Population.

Background: Significant morbidity and mortality are associated with poor asthma control. The aim of this study was to determine factors associated with poor control and referral to specialist secondary care services.

Methods: We used primary care data from the Clinical Practice Research Datalink Aurum (CPRD) linked with Hospital Episode Statistics (HES) records from 1st January 2007 to 31st December 2019.

The operational experience of private owners of small-sized care homes in China: a qualitative study.

Background: Private small-sized care homes (<50 beds)  have proliferated across China, however, until recently little was known about the characteristics of such institutions, and the challenges and the problems faced by their owners. This study aimed to explore the characteristics of small-sized, privately-owned care homes in the People's Republic of China; and to understand the motivation and challenges faced by their owners.

Methods: This study used an interpretative phenomenological analysis approach of qualitative research.