bluuebunny/crossref_metadata_2025_split huggingface dataset:
P162 Cross-validation and complementary value of optical coherence tomography and high frequency ultrasound for the assessment of skin disease in systemic sclerosis
Authors: Karadag Duygu Temiz , Lettieri Giovanni , Picerno Valentina , Gundogdu Ozcan , Padula Maria Carmela , Mennillo Gianna A , Padula Angela A , Galdo Francesco Del , D'Angelo Salvatore , Abignano Giuseppina 
Published: April 2020

Abstract

Background
The modified Rodnan skin score (mRSS) is the current gold standard for skin assessment in systemic sclerosis (SSc) both in clinical trials and practice. Several studies have reported that skin high frequency ultrasound (HFUS) and, more recently, optical coherence tomography (OCT) are able to reflect the severity of the skin disease in SSc. Aim of the study was to compare OCT and HFUS in the assessment of skin involvement in SSc.

Methods
Dorsal forearm skin of consecutive diffuse cutaneous SSc (dcSSc) patients and matched-healthy controls (HC) were scanned using OCT and HFUS by investigators blinded to the clinical details using Vivosight scanner (1 assessor) and Esaote MyLab70 equipped with a 22 MHZ probe (2 assessors) respectively. Minimum Optical Density (MinOD), Maximum OD (MaxOD) and OD at 300 micron-depth (OD300) (OCT) and skin thickness (HFUS) were measured. Clinical involvement was assessed by a blinded operator using the mRSS and results were cross matched with imaging data. Statistical analysis was performed using GraphPad Prism software V.7.0.

Results
A total of 88 OCT images and 176 HFUS images were obtained from 22 dcSSc patients [20 Female, mean age 49 (±11) years, 12 with &lt; 5 years disease duration) and 22 HC (20 Female, mean age 50.7 (±6.7) years]. All OCT measures (MinOD, MaxOD and OD300) were significantly lower in SSc patients than in HC (p = 0.011, p &lt; 0.0001, p &lt; 0.0001 respectively). HFUS showed a lower performance in discriminating SSc skin vs HC compared to OCT (overall AUC 0.6 vs 0.72, 0.8 and 0.89 for MinOD, MaxOD and OD300 respectively). Nevertheless, mean HFUS skin thickness significantly correlated with mRSS at site of analysis (r = 0.47, p = 0.0013) and showed overall excellent interobserver reliability between assessors (ICC &gt;0.8). Importantly, MaxOD and OD300 negatively correlated with HFUS skin thickness (r=-0.32, p = 0.035; r=-0.31, p = 0.039).

Conclusion
OCT of the skin has been previously validated against skin biopsy in SSc. Our results validate HFUS against OCT and indicate that HFUS of the skin is a reliable measure of skin involvement. Further, here we show that HFUS and OCT outperform each other in measuring different aspects of skin involvement in SSc and they offer complementary surrogate outcome measures of disease.

Disclosures
D. Temiz Karadag None. G. Lettieri None. V. Picerno None. O. Gundogdu None. M. Padula None. G.A. Mennillo None. A.A. Padula None. F. Del Galdo None. S. D'Angelo None. G. Abignano None.
P163 Biosamples from at risk SSc patients show classic pathological signs of scleroderma: opportunity for a diagnosis of pre-clinical SSc
Authors: Ross Rebecca L , Georgiou Ioanna , Carriero Antonio , Abignano Giuseppina , Wasson Chris , Migneco Gemma , Herrick Ariane , Denton Chris , Galdo Francesco Del 
Published: April 2020

Abstract

Background
The VEDOSS study has recently indicated that more than 80% of patients affected by Raynaud’s phenomenon (RP) and specific SSc auto-antibodies + capillaroscopy changes satisfied ACR/EULAR 2013 criteria within 5 years.These data suggest that there is a window of opportunity for early detection of SSc in these patients. Here we aimed to determine whether sera, skin biopsies and skin fibroblasts cultured from these patients showed any biomarker sign of SSc.

Methods
Fifty-nine at risk patients identified by having RP and SSc auto-antibodies or capillaroscopy pattern (or both) were enrolled in the national inception cohort (Kennedy Cohort). Sera were tested for IFN inducible chemokines (CXCL-9,10 and 11 and CCL2, 8 and 19) and biomarker of extracellular matrix turnover (ELF test), all previously shown to be increased in SSc. Further, two 3mm skin biopsies were taken from the forearms from 3 ACA+ve (anti-centromere antibodies), 3 SCL70+ve patients. One biopsy was subjected to histology analysis, including haematoxylin and eosin staining and immunohistological staining for Collagen Type 1, alpha-SMA, Caveolin 1 and CD31 as endothelial marker. The other biopsy was used to explant fibroblasts cultures. mRNA and protein were isolated from primary fibroblasts and processed for RT-qPCR and western blotting analyses.

Results
Sera from at risk patients showed overall higher IFN inducible chemokines and ELF test (P &lt; 0.05) with bimodal distribution among patients. Skin biopsies from both ACA or SCL70+ve patients showed decreased number of CD31+ cells, increased number of myofibroblasts and increased collagen bundles within the dermis, as usually seen in SSc, compared to healthy controls. In vitro, fibroblasts from both ACA or SCL70+ve patients showed average 10-fold higher collagen mRNA levels and 31-fold increased collagen protein levels compared to healthy control fibroblasts. Furthermore, fibroblasts from ACA or SCL70+ve patients showed limited TGF-beta induced increase in collagen and SMA expression, similar to SSc fibroblasts.

Conclusion
Although pilot in nature, this study suggests that patients “at risk” already show biomarker signs of SSc both in their sera and at skin biopsy and fibroblast level. Longitudinal studies on patients at this stage of pre-clinical disease may inform on the stratification strategies for imminent progression to clinical manifestations and offer both insights on pathogenesis of clinical signs and a window of opportunity for delaying the onset clinical intervention trials.

Disclosures
R.L. Ross None. I. Georgiou None. A. Carriero None. G. Abignano None. C. Wasson None. G. Migneco None. A. Herrick None. C. Denton None. F. Del Galdo None.
P176 A retrospective analysis of aortitis cases from radiology reports in a London teaching hospital: implications for screening and management
Authors: Townsend Katherine , Cattini Geoff , Moss Katie , Stenson Kate , Holt Peter , Morgan Robert , Sofat Nidhi 
Published: April 2020

Abstract

Background
Aortitis is a heterogeneous rare condition causing aortic inflammation, often due to infectious or autoimmune aetiology. Its presentation, diagnosis and optimal management remain poorly understood, often requiring multidisciplinary input. With the advent of improved imaging techniques, an increasing number of radiology reports are identifying features of vasculitis necessitating clinical investigation. We investigated how cases identified on imaging with features of aortitis reflected clinical diagnosis and treatment. We further examined whether radiological detection of aortitis enables more rapid management decisions to improve outcomes.

Methods
A search was conducted of all radiology reports from St George’s Hospital between 2008 and 2018 for key words indicating “aortitis”, including ‘hyperintense vessel uptake’ and ‘periaortic inflammation.’ From 15,963 initial results, 80 reports were identified with radiological suspicion of aortitis.

Results
Of 80 cases, 36/80 were diagnosed with autoimmune or idiopathic inflammatory pathology: 9 retroperitoneal fibrosis, 8 idiopathic, 7 Takayasu’s, 4 giant cell arteritis, 2 inflammatory aneurysms, 2 Behçet's, 2 IgG4 disease, 1 lupus, 1 granulomatosis with polyangiitis. Diagnosis of autoimmune or idiopathic aortitis was based on symptomatology, imaging, serology, vessel biopsy, and treatment response. 14/80 had infective aortitis: 11 had positive microbiology and 3 demonstrated empirical antibiotic response. Table 1 shows demographics. 12/80 had atheromatous disease. 18/80 were not further investigated due to comorbidity, lack of correlation with symptoms, or absence of follow-up. Initial imaging modalities with the highest yield were computed tomography (CTs) with aorta protocols and CTs of thorax/abdomen/pelvis. The most useful radiology report terms included: aortitis, periaortic inflammation, Takayasu’s, and hyperintense vessel uptake.

Conclusion
Our study is the first retrospective case analysis, to our knowledge, of more than 15,000 radiology reports used as a starting point to evaluate for aortitis, identifying a large dataset with a broad case-mix. It contrasts with current literature identifying cases histologically and post-operatively. We found that radiology can be a useful early alert for possible diagnoses which require further assessment. Consequently, we developed an alerting system within our radiology department based on the search terms and imaging modalities identified. This links to a multidisciplinary meeting including vascular and rheumatology, so highlighted cases are discussed early.

Disclosures
K. Townsend: None. G. Cattini: None. K. Moss: None. K. Stenson: None. P. Holt: None. R. Morgan: None. N. Sofat: None.
P178 Maintenance treatment for ANCA-associated vasculitis in real world practice in the UK: reality of vasculitis remission and relapse and burden of disease
Authors: Worthington David , Rutherford Peter 
Published: April 2020

Abstract

Background
AAV is a relapsing remitting condition and patients are at risk of organ damage from active AAV and therapy especially glucocorticoids (GC). The maintenance phase of AAV is critical for good long-term outcomes. This retrospective study examined maintenance definition, therapy and outcomes in patients in routine clinical practice.

Methods
300 AAV patients managed by 100 UK physicians (40% rheumatologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance between 2014-16 were studied. Data were collected at time maintenance was determined to begin by the physician and at 6, 12, 18 and 36 months.

Results
56% had granulomatosis with polyangiitis; mean age 55.4 years 54% male. 61% had incident AAV and 39% relapsed. Physicians defined time of start of maintenance from treatment start with mean of 4.5 months, on basis of fixed time point 47%, starting new maintenance drug 27%, reaching full remission 16% and no specific criteria 9%. At this time 45% were in full remission vs 49% in partial and 6% refractory. Various maintenance regimes were used, 11% received rituximab (84% 6 monthly and 16% 12 monthly) at varying planned doses 61% 1g, 19% 500 mg and 16% 375 mg/m2, 4% not recorded. Remission rates varied and many patients experienced adverse events (AE) and infections, prolonged GC use was common. At most recent review patients had been followed for a mean of 49.2 months - 6% had died, 30% relapsed at least once, and 10% required renal replacement therapy. 62% had no vasculitis activity and were ANCA negative with 14% still experiencing active disease. 35% still received GCs - 19% &gt; 5mg/ day. There was negative impact on functional status with 13% reducing working hours, 13% restricted social life, 4% leaving employment, 3% registered as disabled and 2% leaving full time education.

Conclusion
Maintenance therapy is variably defined at 4-5 months from start of remission induction therapy. Achieving full remission and preventing relapse are still problems and many patients require GC therapy to maintain remission. Infectious complications are a problem and there is significant negative impact on patient functional status.

Disclosures
D. Worthington Corporate appointments; Employee of Vifor Pharma. P. Rutherford Corporate appointments; Employee of Vifor Pharma. Shareholder/stock ownership; Vifor Pharma.
P184 Developing a pathway for tocilizumab treatment in giant cell arteritis: a South London regional experience
Authors: Saha Pratyasha , Sandhu Virinderjit , Robinson Helena , Ezeonyeji Amara , Al-Shakarchi Israa , Chander Sumeet , Suresh Resmy , Kaul Arvind , Sofat Nidhi 
Published: April 2020

Abstract

Background
Tocilizumab is now approved by the National Institute of Health and Care Excellence (NICE) for up to a year in relapsing or refractory giant cell arteritis (GCA). The practicalities of developing a pathway for referral using a hub and spoke model were previously unknown. Here we discuss our novel experiences utilising tocilizumab for GCA in its first year of licensing, after the introduction of a new regional multi-disciplinary team referral pathway.

Methods
We assessed all patients started on tocilizumab for GCA between August 2018-May 2019. The central assessing hub is St George’s University Hospitals NHS Foundation Trust, a large tertiary rheumatology department in the South of England, serving a population of 1.3 million.

Results
As per Table 1 below. A total of 9 patients were identified: 6 female and 3 male, with an average age of 74.2 (range 63-80). 5 patients were referred internally from clinicians at St George’s Hospital, with the remainder from local district general hospitals. Steroid protocols between patients were varied, and two-thirds required a 3-day IV methylprednisolone course, including all 4 patients with visual symptoms. A third of patients were on concurrent methotrexate, a disease-modifying antirheumatic drug. 8 of 9 patients were on alendronate, vitamin D/calcium, and a gastroprotective agent, and 7 were on aspirin. Reported side effects from steroids were common, with weight gain, increased appetite and osteoporosis noted. All our 9 patients continue their tocilizumab injections, with one individual having a 3-month break for a routine hip operation, and another a 1-month hiatus due to temporary derangement in liver function tests. Tocilizumab proffered improved disease control and few side effects were noted. 3 patients have now been on tocilizumab for 12 months and raise interesting discussions about ongoing funding and treatment efficacy.

Conclusion
Our case series shows the development and delivery of an effective hub and spoke referral pathway for tocilizumab treatment in GCA. We show that steroid dosing could be reduced with tocilizumab, and that all subjects received full funding for treatment. Our referral pathway has encouraged the uptake of the IL-6 monoclonal antibody treatment for GCA and compliance with NICE guidelines.

Disclosures
P. Saha None. V. Sandhu None. H. Robinson None. A. Ezeonyeji None. I. Al-Shakarchi None. S. Chander None. R. Suresh None. A. Kaul None. N. Sofat None.
P186 Efficacy and safety of rituximab in the treatment of systemic vasculitis: experience at a single centre
Authors: Orr Carl , Verdiyeva Ayna , Ahmad Nadia , Ariff Hairulhadi , Luqmani Raashid 
Published: April 2020

Abstract

Background
Rituximab is a monoclonal chimeric antibody targeting the mature B cell molecule CD20, expressed on the cell surface. It is licenced and widely used in the treatment of autoimmune diseases, including the ANCA associated vasculitides and rheumatoid arthritis. The efficacy and safety of rituximab in rare diseases requires ongoing appraisal.

Methods
We interrogated the records of 62 consecutive patients treated with rituximab for small vessel systemic vasculitis at our unit over the last 3 years, using a contemporaneously maintained central database, as well as individual electronic patient records.

Results
The patient demographic data, and main results are presented in Table 1. 31 (50%) of the patients treated with rituximab were female, and the indication for treatment in most cases was ANCA associated vasculitis (77.4%). After a mean follow up period of 2.04 years, the mean reduction in BVAS was 1.64 (3.83). 5 severe adverse events were recorded, defined as death or hospitalisation potentially related to treatment with rituximab. 3 patients died of respiratory sepsis, 1 experienced a wound infection, and 1 experienced an ischaemic colon. Four patients were noted to have low immunoglobulins.

Conclusion
Rituximab is an effective treatment for many patients with systemic, small vessel vasculitis. Understanding the safety profile of this drug in the context of our cohort is challenging, given the significant morbidity associated with the underlying disease, as well as the age profile and concomitant immunosuppressive medications. Continued surveillance regarding efficacy and safety of rituximab in the small vessel systemic vasculitides remains invaluable.

Disclosures
C. Orr None. A. Verdiyeva None. N. Ahmad None. H. Ariff None. R. Luqmani None.
P212 The effect of body weight in response to subcutaneous tocilizumab in patients with RA
Authors: Davies Rebecca , Vivekanantham Arani , Lunt Mark , Watson Kath , Hyrich Kimme L , Group BSRBR-RA Contributors , Bluett James 
Published: April 2020

Abstract

Background
Tocilizumab is an IL-6 receptor humanised monoclonal antibody treatment option in rheumatoid arthritis (RA) who have not responded or are intolerant of disease modifying anti-rheumatic drugs (DMARDs) or other biologics. Tocilizumab was available initially as an intravenous preparation, dosed according to weight, and more recently as a subcutaneous (SC) preparation given at 162mg/weekly irrespective of body weight. Obesity is highly prevalent in RA and there has been concern that starting or switching patients to SC tocilizumab could reduce its effectiveness in those patients with a higher body weight. The objective of the current study is to investigate the relationship between body weight and DAS28 response at 6 months in tocilizumab naïve RA patients starting SC tocilizumab.

Methods
The study population comprised RA subjects recruited to the BSRBR-RA up to 30/11/2018 commencing SC tocilizumab for the first time. Patients had to be tocilizumab naïve and have at least one six monthly study follow-ups recorded after starting tocilizumab. Baseline characteristics at point of starting tocilizumab are described. Linear regression, fully adjusted for relevant confounders, was used to investigate the relationship between change in DAS28 score from baseline to six months and body weight per ten kilograms (kg), and in a separate analysis, as BMI category. Multiple imputation was used to handle missing data.

Results
Three hundred and fifteen patients starting SC tocilizumab were eligible for analysis. The median age was 60 years, majority were female, and had median disease duration of 11 years at baseline. Seventy percent had prior biologic exposure. Median weight was 76kg, and the majority of patients were categorised as normal weight (37%) or pre-obesity (31%) according to BMI. Median DAS28 score was 5.5 at start of treatment with median improvement after 6-months of 2.0 units. The fully adjusted linear regression model showed no association between body weight or BMI and change in DAS28 score at six months (Table 1).

Conclusion
Data from this study show that body weight does not appear to affect initial response to SC tocilizumab. This is reassuring given that patients are likely to be given subcutaneous tocilizumab due to ease of administration and reduced hospital costs.

Disclosures
R. Davies None. A. Vivekanantham None. M. Lunt None. K. Watson None. K.L. Hyrich None. J. Bluett None.
P240 Can ultrasound alone predict the need to treat ACPA positive individuals without synovitis?
Authors: Duquenne Laurence M , Mankia Kulveer , Montoya Leticia Garcia , Matteo Andrea Di , Nam Jacqueline , Emery Paul 
Published: April 2020

Abstract

Background
In anti-cyclic citrullinated peptide antibody-positive (ACPA+) individuals without clinical synovitis (at-risk), to define the critical ultrasound (US) features sufficiently predictive for inflammatory arthritis (IA) to enable logical initiation of therapy.

Methods
In a single centre prospective cohort, at risk ACPA+ individuals with a new musculoskeletal symptoms underwent an US scan of 38 joints and 18 tendons at first visit. The predictive value of US abnormalities (Power Doppler (PD), Grey Scale (GS), erosion or tenosynovitis (TSV)) for progression to IA was analysed and the best predictive joints determined by Multivariable Cox Regression, adjusted for confounders. The US results were combined with clinical symptoms/findings to produce predictive models.

Results
Consecutive at-risk ACPA+ individuals (n = 457, mean age 50.3 years old, 74.2% women) were followed up for median of 15.4 months (range 0.1-127.4), a complete dataset with follow-up of at least 6 months was available for 319 of them. 135 (29.5%) developed IA after a median of 11.3 months (range 0.1-111.7). The negative predictive value of a US scan without any abnormality was 82%. In multivariable Cox regression, both PD and TSV were predictive of progression, with respectively hazard ratios of 1.2 (9=0.026) and 1.13 (p = 0.025). All US abnormalities had a high specificity (spec) but only moderate sensitivity (sens), PD was the most specific with a spec/sens of 0.94/0.23, followed by TSV with a spec/sens of 0.91/0.26 but the best area under the curve (AUC) of 0.599 (P = 0.0015). The addition ACPA titre (high compared to low), but not GS, improved spec/sens up to 0.92/0.34 and AUC to 0.964 (p &lt; 0.001). A selection of US and clinical data of 14 joints also improved prediction, with an AUC of 0.670 (p &lt; 0.001) and a spec/sens of 0.65/0.62. A selection of the 34 most predictive features reached the same sens/spec as the ACR/EULAR 2010 classification criteria for RA, showing a spec/sens of 0.80/0.56.

Conclusion
In at-risk ACPA+ individuals, the presence of sub-clinical US abnormalities are highly specific for progression to IA. The only moderate sensitivity can be improved by using joints or features selection in combination with clinical examination. These results are the first step in providing guidance for which at-risk ACPA+ individuals to treat.

Disclosures
L.M. Duquenne None. K. Mankia None. L. Garcia Montoya None. A. Di Matteo None. J. Nam None. P. Emery None.