bluuebunny/crossref_metadata_2025_split huggingface dataset:
P136 KL6 and IL-18 levels are negatively correlated with respiratory function tests and interstitial lung disease extent assessed on high-resolution computed tomography in patients with systemic sclerosis-related interstitial lung disease
Authors: Santos Cristiana Sieiro , Calleja Antolín Sara , de la Calle Lorenzo Javier , Bollo de Miguel Elena , Díez Álvarez Elvira 
Published: April 2024

Abstract

Background/Aims
Serum biomarkers have been suggested as indicators for pulmonary damage with clinical value in the diagnosis and prognosis of SSc-ILD. We aim to investigate the role of serum biomarkers (Krebs von den Lungen-6 KL-6, IL-18 and IL- 18BP) as potential biomarkers reflecting the severity of SSc-ILD as assessed through high-resolution computed tomography (HRCT) and pulmonary function tests (PFT).

Methods
A cross-sectional study including patients with SSc fulfilling the 2013 ACR/EULAR criteria was performed. Patients were classified according to disease duration and pulmonary involvement. All SSc patients underwent chest HRCT scans and pulmonary function test at baseline. Serum concentration of KL-6, IL8 and IL18BP were determined usingsandwich ELISA technique (solid phase sandwich Enzyme Linked-Immunosorbent Assay), with kits from MyBiosource for KL-6 and from Invitrogen for IL18 and IL18BP. A semiquantitative grade of ILD extent was evaluated through HRCT scan (grade 1, 0-20%; grade 2, &gt;20%). Extensive lung disease was defined as &gt; 20% of lung involvement on HRCT, and FVC &lt;70% predicted and limited lung involvement as ≤ 20% of ILD involvement on HRCT,and an FVC ≥70% predicted.

Results
74 patients were included, 27% were male, with a mean age of 57.5±15 years. 28 patients had ILD (38%). 64 % of patients had &lt;20% of ILD extent classified through HRCT scan. SSc-ILD patients had elevated serum KL- 6 and IL-18 levels compared to patients without ILD (p = 0.003 and p = 0.04). A negative correlation between KL-6 levels and %FVC (β=-0.25, p 0.037) and %DLCO (β=-0.28, p 0.02) and between IL-18 levels and %FVC (β=-0.20, p 0.03) and %DLCO (β=-0.14, p 0.04) were found. Serum KL-6 and IL-18 levels successfully differentiated grades I and II (p = 0.028 and p = 0.021). Semiquantitative grades of ILD on the HRCT scan were significantly proportional to the KL-6 (p 0.01) and IL-18 (p = 0.03). A positive correlation between extensive lung disease and KL-6 (β = 0.61, p 0.007) but not with IL-18 was found.

Conclusion
Serum KL-6 levels and IL-18 were increased in patients with SSc-ILD and showed a positive correlation with ILD severity as measured using a semiquantitative HRCT grading scale and a negative correlation with PFT parameters.

Disclosure
C. Sieiro Santos: None. S. Calleja Antolín: None. J. de la Calle Lorenzo: None. E. Bollo de Miguel: None. E. Díez Álvarez: None.
P142 Effect of Atorvastatin on vascular endothelial function in early Systemic Sclerosis: An open label Randomized Controlled trial
Authors: Das Anna C , Thabah Molly M , Mariaselvam Christina Mary , Vijayan Rubini , Anantharaj Avinash , singh Negi Vir 
Published: April 2024

Abstract

Background/Aims
Systemic Sclerosis (SSc) is driven by early endothelial dysfunction, leading to loss of endothelium-dependent vasodilatation. This predisposes to increased stiffness of large arteries. Prospective studies have found a conflicting role of statins in improving vascular function in established SSc. We undertook this study to explore if statins influence endothelium dependent vasodilation in early SSc

Methods
In this single center open label randomized controlled trial between July 2021 to January 2022, SSc patients (ACR-EULAR 2013) between 18-65 years, with duration &lt; 3 years from the first non-Raynaud’s symptom were included. Those with complicated Raynaud’s, overlap syndromes and cardiovascular comorbidities were excluded. Participants were randomized into statin (atorvastatin 40 mg/day/A40) or no -statin arm. Both groups received stable doses of immunosuppression, during the study period. The primary outcome of flow-mediated dilation (FMD %) of brachial artery, measured by single assessor and secondary outcomes of common carotid intima medial thickness (CIMT), modified Rodnan Skin score (mRSS), Raynaud’s visual analogue scale (RayVAS:0-10), hs CRP, von Willebrand factor and oxidized low-density lipoproteins were measured at baseline and 16 weeks. All patients provided written informed consent; study protocol was approved by IEC(JIP/IEC/2020/026). Considering a change in FMD of 1% between arms as clinically meaningful, sample size was calculated to be 144. Analysis was performed using SPSS v.19.CTRI registration no: REF/2020/07/03495

Results
Total 71 eligible patients were randomized into statin(n = 36) and no-statin(n = 35) arms. Baseline parameters were comparable between arms. Baseline mRSS was 14.25. On per-protocol analysis of statin (n = 28) and no-statin (n = 32) arms, there was no significant difference in FMD either at baseline or at 16 weeks (table 1). At week 16, basal brachial artery diameter increased (p = 0.008) in statin arm. Ray VAS scores improved in the statin arm,not achieving significance(p = 0.15). An increase in mRSS from 14 to 16 was noted in no-statin arm , whereas it remained stable in the statin arm (14.5). Secondary endpoints were not met. No adverse events were noted.

Conclusion
In early SSc, atorvastatin 40 mg/day, added to background immunosuppression, failed to improve endothelial function, assessed using brachial FMD, at 16 weeks. Stabilization of skin tightening was noted in the statin arm.

Disclosure
A.C. Das: None. M.M. Thabah: None. C. Mariaselvam: None. R. Vijayan: None. A. Anantharaj: None. V. Negi: None.
P178 CXCL12/CXCR4-mediated osteogenic precursor cells recruitment: a key mechanism in ankylosing spondylitis-associated pathological bone formation
Authors: Cui Haowen , Liu Hui 
Published: April 2024

Abstract

Background/Aims
Ankylosing spondylitis (AS) is a debilitating condition characterised by severe spinal deformities, inflammation, and excessive bone formation, imposing significant socioeconomic burdens. Current treatments alleviate symptoms but fail to address bone structural damage. Pathological bone formation often occurs at entheses, where tendons and ligaments connect to bone. Osteogenic precursor cells (OPCs) play a crucial role, but their migration to new bone sites is poorly understood. C-X-C motif chemokine ligand 12 (CXCL12) is implicated in cell migration and bone-related processes, but its role in AS remains unclear. This study explores CXCL12/CXCR4 signalling in OPC recruitment and new bone formation, providing insights into AS pathogenesis and potential therapeutic targets.

Methods
We established mouse models, including the DBA/1 model, lipopolysaccharide-induced spondyloarthritis model, and Achilles tendon semi-transection model to confirm the role of CXCL12-Induced OPCs migration in pathological new bone formation. Additionally, genetically edited mouse models were generated to confirm the underlying mechanism of OPCs migration and their spatiotemporal phenotypes of differentiation, including DBA1;CXCL12 col2 transgenic mice, CXCL12hi/hi;Col2a1-creERT mice, and CXCR4fl/fl;Prx1-creERT mice.

Results
In this study, we have identified CXCL12 as a crucial contributor to the initiation of pathological new bone formation by recruiting OPCs. CXCL12 was highly expressed in regions predisposed to pathological bone development, attracting OPCs to these upregulated areas. Inhibiting the CXCL12/CXCR4 axis with AMD3100 or the conditional knockout of CXCR4 effectively reduced OPC migration and subsequent pathological bone formation in animal models of AS. Overexpression of CXCL12 in genetically engineered animals with a DBA/1 background demonstrated a stable joint ankylosis phenotype, providing a valuable model for the study of AS. Furthermore, our research revealed the indispensable role of Rac1 in OPC migration and the ensuing pathological bone formation.

Conclusion
This study elucidates the novel role of CXCL12 in AS and offers potential strategies for targeting the CXCL12/CXCR4-Rac1 axis to prevent the progression of axial skeletal ankylosis.

Disclosure
H. Cui: None. H. Liu: None.
P181 Clinical assessment of radiologically defined clinically isolated aortitis in a single centre study
Authors: Jain Sahil , Muñoz-Urbano Marcela , Khormi Abdulrahman , Sangle Shirish , D'Cruz David 
Published: April 2024

Abstract

Background/Aims
Aortitis may occur in the absence of systemic vasculitis and is termed clinically isolated aortitis (CIA). Our purpose was to describe a cohort of patients with CIA and compare their characteristics with aortitis patients associated with rheumatic diseases.

Methods
We conducted a retrospective analysis of 32 patients with non-infectious aortitis evaluated in our centre. Online records were analysed. We included demographic variables, symptoms, laboratory data, imaging, treatment, outcomes, and mortality. The description of quantitative variables was made using percentages and medians with interquartile range (IQR).

Results
Out of 32 patients, 10 were classified as CIA and 22 had other inflammatory diseases (approx. 1:2 ratio) - fourteen had giant cell arteritis, 4 had Takayasu's arteritis, 2 with granulomatosis with polyangiitis, 1 each with IgG4 related disease and ankylosing spondylitis, classified according to the ACR/EULAR criteria for each disease. All patients underwent PET-CT imaging confirming isolated aortitis; none had an artery biopsy. Table 1 shows the main clinical characteristics. Among the CIA patients, the median duration of follow-up was 65 months (IQR 42-72). Three patients were asymptomatic and seven had constitutional symptoms (fever, weight loss, sweats, fatigue). Only one patient reported abdominal, back pain. The diagnosis was incidental in two cases. All patients had negative infection screen and serological markers for other rheumatologic conditions. Six (60%) patients had involvement only of the abdominal aorta, 2 had only thoracic aorta, and 2 had abdominal and thoracic aortitis. Six patients (60%) were treated with glucocorticoids (GCs) and methotrexate, 2 with GCs alone, 1 with GCs and mycophenolate mofetil, and 1 patient had resistant disease requiring tocilizumab. Four patients had follow-up PET-CT imaging: 2 showed reduction in FDG avidity, 1 had a stable tracer uptake, and 1 had no evidence of persistent aortitis. All the CIA patients demonstrated clinical and biochemical (ESR/CRP) improvement and at follow-up.

Conclusion
Our CIA patients had a male predominance, between the sixth and seventh decades, consistent with the previous literature. Aneurysms are more common in CIA patients than in those with GCA or TAK. There is no fixed protocol for CIA but conventional DMARDs and glucocorticoids are helpful.

Disclosure
S. Jain: None. M. Muñoz-Urbano: None. A. Khormi: None. S. Sangle: Other; Principle Investigator for HAVEN Trial. D. D'Cruz: Consultancies; GlaxoSmithKline, CSL Vifor. Grants/research support; Medical Research Council, National Institute for Health and Care Research. Other; Principal Investigator Clinical trials with Pfizer. Eli Lilly, AbbVie, Syneos, Idorsia.
P190 Protocolised ultrasonography led pathway has a high sensitivity for diagnosis of primary large vessel vasculitis
Authors: Mukhtyar Chetan B , Ducker Georgina , Beadsmoore Clare , Sisson Katherine , Jones Colin 
Published: April 2024

Abstract

Background/Aims
Ultrasonography (US) for diagnosis of large vessel vasculitis (LVV) is a recommended first line diagnostic procedure. Our county has an annual incidence of 57.5/million for primary LVV (giant cell arteritis (GCA) 48.3/million; Takayasu 2.5/million; unclassified LVV 6.4/million). Our protocolised fast-track US pathway has reduced visual loss from 18.7% to 11.5%. We present the results of our first 1000 unique referrals.

Methods
Unique requests for US from January 2017 were analysed. Protocolised US examination of the arteries includes superficial temporal artery (STA) and its rami, followed by the entire axillary artery, followed by other arteries as necessary. Halo sign in at least two different arteries was needed for diagnosis of LVV. A temporal artery biopsy (TAB) or positron emission tomography (PET) were requested if the US was negative AND CRP was ≥20mg/L (or missing) AND an alternate explanation for the raised CRP was not immediately apparent. For those where a second test was not requested OR if it was negative, prednisolone was tapered rapidly, and a patient-initiated follow-up allowed rapid re-assessment. If referring physician or patient did not want a second test, GCA was diagnosed on clinical grounds alone and the pathway was considered to have failed.

Results
Median age was 73 (IQR 13); 11/1000 referrals were for people &lt;50 years of age. The median delay for the procedure was 4 (IQR 4) days. Prednisolone had been started a median of 4 (IQR 5) days previously. 279/1000 (28%) US scans demonstrated vasculitis. Pre-steroid CRP was ≥20mg/L in 283 cases and unavailable in 7. An alternate explanation for the raised CRP was found in 102 cases, 181 were referred for a second test, and 7 received a clinical diagnosis of GCA without a second test. The second test was diagnostic in 31/181 (17%) - 24/139 (17%) TAB, 7/42 (17%) PET. 3/150 cases with a negative second test and 4/431 cases with CRP &lt;20mg/L were diagnosed with GCA on patient-initiated follow-up. The delayed diagnosis did not result in visual loss. 202/279 (72%) US positive cases had bilateral STA involvement. The addition of axillary artery imaging picked up a further 53 (19%) cases; 24/279 (9%) cases needed imaging of other arteries. The sensitivity and negative predictive value of the pathway are 96% (310/324) and 98% (683/690) respectively.

Conclusion
Our protocolised US led pathway for diagnosis of LVV is highly sensitive and allows disease exclusion with high certainty. Routine US of the superficial temporal artery and its rami, and the entire axillary artery provide diagnosis in 91% of cases but ability to scan more arteries improves yield in a further 9% of cases. Composite testing with US plus second test, stratified by CRP levels, can be recommended as a gold standard diagnostic tool for LVV.

Disclosure
C.B. Mukhtyar: None. G. Ducker: None. C. Beadsmoore: None. K. Sisson: None. C. Jones: None.
E004 Question of the month; a simple method of patient engagement
Authors: Waller Rosemary 
Published: April 2024

Abstract

Background/Aims
Patient involvement at every stage of service development is key to driving forward meaningful change. It can however, be difficult to engage a broad demographic. Focus groups can gain in depth information but are time consuming and will only involve a small number of people. Questionnaires are often poorly completed or have a low return rate. Asking a ‘question of the month’ is a simple method of collecting a large amount of data on a single topic. We have recently reinstated patient education sessions following a break in their provision due to Covid-19 and were keen to optimise these by finding out what patients wanted.

Methods
A poster was place in the waiting room asking ‘What was the most useful information you were given when you were diagnosed with arthritis’. Patients were given a post-it note and asked to write an answer on it and stick it onto the poster. The same question was asked in paediatric, adolescent and general adult clinics to all follow up patients with inflammatory arthritis during September 2023. The question of the month concept was developed by the Rubis QI Team as part of the JIALearn project. Thematic analysis was performed for the three age groups separately.

Results
Themes common to all age groups: 1. Knowing that there are a range of effective treatment options available. 2. Hope: “it is not life changing”, “expect a long journey and try and remain positive” In paediatrics, effective, accessible communication was a dominant theme in “any concerns are important and are listened to” In adolescents and young adults being given hope and knowing that there were treatment options were the most dominant themes: “it doesn’t have to affect your life”, “knowing I had different choices out there to help me” In adults the most dominant theme was around self management, particularly around regular exercise, diet and weight loss. “I can manage my problem”, “allows you to stay in control”. Some patients used this project as an opportunity to leave positive feedback about their care to date. Clinicians involved reported good clinical engagement and an improved therapeutic relationship with patients. These themes will be used to guide future patient education sessions targeted at specific age groups. The results of this project will be developed into a poster for the waiting room to demonstrate that comments have been listened to and acted upon.

Conclusion
Adults newly diagnosed with arthritis place a strong emphasis on self management. The themes of open communication and hope emerged in children and young adults. The comments provided will help to guide and shape future patient education sessions. Question of the month is a simple way of engaging with a broad number of patients.

Disclosure
R. Waller: None.
E009 An audit looking into bisphosphonate co-prescription and compliance in patients with giant cell arteritis
Authors: Bolger Alistair A , Hutton Lisa 
Published: April 2024

Abstract

Background/Aims
The treatment of giant cell arteritis includes glucocorticoid use to reduce inflammation. There are known drawbacks of long-term glucocorticoid use, including osteopenia and osteoporosis. The British Society for Rheumatology giant cell arteritis guidelines recommend that we should consider appropriate pharmacological bone protection at the time of presentation to counteract this. Glucocorticoid toxicity risks increases with both dosage and duration of steroid use. To reduce steroid burden, we consider introduction of the steroid sparing agents such as tocilizumab and methotrexate. This audit was to look into whether we were locally achieving bone protection consideration and to whether steroid sparing agents were helping in terms of compliance of bisphosphonates.

Methods
We retrospectively looked at the clinical letters of the patients locally diagnosed with giant cell arteritis in the previous 3 years to ascertain whether there was documentation of decisions around starting bisphosphonates at the time of diagnosis and whether the patients tolerated bisphosphonate therapy for the recommended duration. Patients were classified into 3 groups, as to whether their treatment was glucocorticoids with tocilizumab (TOC), glucocorticoids with methotrexate (MTX) or glucocorticoid monotherapy (MONO).

Results
49 Patients were identified. 3 of these patients were excluded for various reasons. 17 were in the TOC group, 11 in the MTX group, and 18 in the MONO group. Documentation of consideration of bisphosphonates at diagnosis was 94% in TOC, 91% in MTX and 100% in MONO. Overall this was 96%. Compliance of bisphosphonate therapy for the recommended duration was 88% in TOC, 90% in MTX and 86% in MONO. Overall compliance was 88%. There was no statistically significant difference between the steroid sparing groups and the monotherapy group both in terms of consideration of initiation of bisphosphonate treatment and compliance of bisphosphonate treatment, with p values of 0.52 and 0.8 respectively.

Conclusion
Overall, we found that locally there was good consideration of bisphosphonate therapy at diagnosis and that compliance remained good throughout treatment. This can help reduce the side effect profile of glucocorticoid toxicity. Although, there was no statistically significant difference in our study of concordance of bisphosphonates between the two groups, steroid sparing agents are useful in our arsenal at reducing the risks of glucocorticoid toxicity.

Disclosure
A.A. Bolger: None. L. Hutton: None.
E010 Impact of rheumatologist ultrasound clinic on the management of inflammatory arthritis at a tertiary centre rheumatology department
Authors: Murad Awin Mohammed , Jubber Ameen , Moorthy Arumugam 
Published: April 2024

Abstract

Background/Aims
Musculoskeletal ultrasound plays an important role in the assessment and management of inflammatory arthritis, enabling early diagnosis and prompt initiation of disease modifying therapy, as well as escalation of therapy as part of a treat-to-target strategy. It can help clinicians distinguish between true joint inflammation and non-inflammatory causes of increased pain scores. We reviewed our weekly rheumatology ultrasound clinic service where patients are referred to aid in clinical decision making. The study aimed to evaluate the cohort of patients attending the rheumatology ultrasound clinic at University Hospitals of Leicester, a busy tertiary centre, serving a multi-ethnic population, and to assess the impact of this clinic on the management of inflammatory arthritis in these patients.

Methods
Data was collected retrospectively from the ultrasound clinic at University Hospitals of Leicester between June 2022 and June 2023. Outcome measures included: date of scan request, date of scan, underlying disease, C - reactive protein (CRP), anti-CCP level, presence of radiographic erosions, presence of active synovitis or erosions on ultrasound, other rheumatologic disease and how the ultrasound findings changed the patient’s management.

Results
The total number of patients attending the clinic during the study period was 91. Of these, 70% were female and 30% male. Over the study period, 11.8% of patients did not attend their appointment. At the time of referral, 68% of patients had a CRP&lt;5, 91% had a negative anti-CCP and 83% had no radiographic erosions. Following the scan, 13% of the patients had active synovitis, and 10% received at least one steroid injection. Interestingly, 86% had no active inflammation and no indication to escalate their disease modifying drug. In our patient cohort, 16% had pre-existing fibromyalgia. In all appointments, the clinician performing the scan showed the ultrasound images to the patient and explained the findings.

Conclusion
This ultrasound clinic is a key part of the treat-to-target strategy for inflammatory arthritis, enabling escalation of disease modifying therapy where indicated. It allows ultrasound guided and marked injections to be given when needed and identifies patients with non-inflammatory causes of increased pain scores, preventing patients from receiving unnecessary immunosuppression.

Disclosure
A. Mohammed Murad: None. A. Jubber: None. A. Moorthy: None.