bluuebunny/crossref_metadata_2025 huggingface dataset:
OA11 Serum interferon alpha levels as a predictor of short-term mortality in patients of SLE with high disease activity
Authors: Yerram Keerthi Vardhan , Devarasetti Phani Kumar , Rajasekhar Liza
Published: April 2022

Background/Aims

Short-term mortality in patients with SLE and high disease activity approaches 30% as reported by various studies. Raised serum interferon-alpha levels are observed in patients with active SLE. In mice studies interferon alpha(IFNα) delivered through adenovirus vector to lupus prone mice, caused rapid development of glomerulonephritis and death within 18 weeks. The aim was to study the value of interferon alpha in predicting short-term mortality in patients of SLE with high disease activity.

Methods

Serum samples of consecutive SLE patients with high disease activity (SLEDAI>12) and age more than 18 years admitted in NIMS Rheumatology ward and acute medical care (AMC) were analyzed for interferon alpha levels with IFNα ELISA kit (ELAB science). Patients admitted for any other reason and having SLEDAI less than 12 were excluded. Demographic details and SLEDAI were recorded simultaneously. Patients who survived and discharged were considered as survivor group and those who succumbed during admission were considered as non-survivors. Between groups, difference in mean interferon alpha level was calculated using unpaired t test. Binomial logistic regression was applied to IFNα levels, dsDNA and SLEDAI as for predicting in-hospital mortality. Using ROC curve, area under curve was calculated for IFNα as a predictor of in-hospital mortality. Patients or legal guardian provided written informed consent for the study. Study was approved by the Institute ethics committee.

Results

Seventy patients with SLEDAI >12 were admitted to ward (n = 62) or AMC (n = 18) from November 2020 to August 2021.Those excluded were age<18 (n = 6), SLEDAI<12 (n = 10), overlap syndromes (n = 8), patients with infection (n = 11). Mean age of the patients was 27.6±8.9 years. Mean duration of hospitalization was 8±4 days. 12 patients died in hospital and 58 survived. Mean days to death was 5±1 days. Mean SLEDAI (23.6±6.1, 18±5.6 p = 0.05), mean dsDNA (3.1±2.1, 1.7±1.8 p = 0.05) and mean serum IFNα levels in pg/ml (318.8±190.1, 39.9±74.7 p = <0.001) was higher in non-survivors than survivors. On applying binomial logistic regression, serum interferon alpha predicted in-hospital mortality (p = <0.001) while dsDNA(p = 0.4) and SLEDAI (p = 0.5) did not. Area under curve for predicting death was 0.9 for IFNα,0.74 for SLEDAI and 0.7 for dsDNA. A serum interferon alpha level of 140 pg/ml was the best predictor of in-hospital mortality with sensitivity of 84 %and specificity of 94%.

Conclusion

In-hospital mortality in patients with high disease activity is 17%. dsDNA, SLEDAI and serum interferon levels are predictors of in-hospital mortality. Among these serum IFNα is the best predictor of in-hospital mortality.

Disclosure

K. yerram: None. P. Devarasetti: None. L. Rajasekhar: None.
OA14b Etanercept originator versus its biosimilar (SB4) for the treatment of rheumatoid arthritis. Are they truly similar?
Authors: Rokad Aasiyah , Kearsley-Fleet Lianne , Watson Kath , Lunt Mark ,   BSRBR-RA, Hyrich Kimme L
Published: April 2022

Background/Aims

Etanercept biosimilar SB4 (ETN-B) showed comparable efficacy to its biologic originator (ETN-O) among biologic-naïve patients with rheumatoid arthritis (RA) in randomised controlled trials. Subsequently, a nationwide guideline in the United Kingdom (UK) obligated the prescription of biosimilars in 2016, resulting in significant cost-savings to the NHS. However, real-world evidence comparing ETN-O and ETN-B is limited. This analysis aims to compare the effectiveness of ETN-O versus ETN-B amongst biologic-naïve patients with RA treated in routine clinical practice in the UK.

Methods

The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective observational cohort study. This analysis included patients starting their first biologic (ETN-O or ETN-B), recruited since 2010, with at least one follow-up. Baseline data are collected at start of therapy, including patient demographics and disease activity. Follow-up data are collected six monthly for the first three years and annually thereafter, including changes in disease activity and anti-rheumatic therapy. Key outcomes assessed were change in Disease Activity Score for 28-joints (DAS28), DAS28 remission, EULAR treatment response, change in Health Assessment Questionnaire (HAQ), and minimal clinically important difference (MCID) in HAQ. Drug retention was explored using Kaplan-Meier and Cox-regression analyses, along with reasons for treatment withdrawal. Multiple imputation was used to account for missing data and confounding by indication was accounted for using propensity-decile adjustment.

Results

This analysis included 1927 patients with RA starting their first biologic therapy: 996 (52%) ETN-O and 931 (48%) ETN-B. At six-months, change in DAS28 and HAQ were similar between therapies (Table). There were no differences in key imputed propensity adjusted outcomes (odds ratio [95% confidence interval]): DAS28 remission: 0.90 (0.7-1.1, p = 0.3); MCID in HAQ: 0.86 (0.7-1.1, p = 0.3) and EULAR treatment response: 0.96 (0.8-1.2, p = 0.8). One-year retention rates were 69% (95% CI: 66-72) for ETN-O and 70% (95% CI: 67-73) for ETN-B and the main reasons for treatment withdrawal were adverse events and ineffectiveness for both drugs.

Conclusion

This analysis is the first to our knowledge to show similar outcomes amongst biologic-naïve patients with RA treated with either ETN-O or ETN-B using real-world data, which brings further evidence for similarity between the drugs.

Disclosure

A. Rokad: None. L. Kearsley-Fleet: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.
OA15 Drivers of change in four and two component disease activity scores after etanercept treatment, in a multi-centre cohort of patients with established rheumatoid arthritis
Authors: Stadler Michael , Ling Stephanie , Nair Nisha ,   BRAGGSS, Isaacs John , Hyrich Kimme , Morgan Ann , Wilson Gerry , Plant Darren , Bowes John , Barton Anne
Published: April 2022

Background/Aims

Treatment response in RA is measured by different disease activity scores (DAS28). The widely used 4 component (4C) DAS28 does not always correlate with synovitis, and a new 2 component version (2C) DAS28 has been developed to address this problem. Here, we use multivariable linear regression models to identify drives of change (Δ) in 4C and 2C DAS28 after 3 months on the anti-TNF drug etanercept (ETN).

Methods

Using data from the Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS), we identified patients treated with originator or biosimilar ETN (N = 773). Differences between the follow-up (FU) and baseline (BL) DAS28, adjusted for baseline, serve as outcome variables. Multiple imputation by chained equations was used to impute missing data, and models were internally validated via bootstrapping. Table 1 shows the baseline statistics, and model parameters for the included covariates.

Results

We found that 15.8% (95% CI: 11 - 20.6%) of the variance in Δ4C was explained by the baseline DAS28, compared to 26.3% (95% CI: 20.9 - 31.7%) for the Δ2C. Age of onset, HAQ score and concurrent DMARD treatment were significantly associated with both ΔDAS28 scores. Δ4C-DAS28 was additionally associated with first biologic use, seropositivity for either rheumatoid factor or anti-citrullinated peptide antibodies, and the Hospital Anxiety and Depression Scale-Anxiety score. The only additional predictor significantly associated with Δ2C-DAS28 was weight. After adjusting for baseline DAS28, the additional clinical covariates only explained 7.6% (IQR: 7.3 - 7.8%), and 2.3% (IQR: 2.0 - 2.6%) of the variance for the 4C- and 2C-DAS28, respectively.

Conclusion

ΔDAS28 is heavily influenced by the baseline DAS28, and additional clinical covariates explain little to none of the additional variance. Notably, known factors associated with treatment response, such as seropositivity and previous unsuccessful treatments, were only significant for the 4C-DAS28. This suggests that the 4C DAS and 2C DAS capture different aspects of RA disease progression. Further association studies are required to find other reliable predictors for ΔDAS28, which may include biological markers of response. Significant covariates identified here should be considered as potential confounding factors.

Disclosure

M. Stadler: None. S. Ling: None. N. Nair: None. J. Isaacs: None. K. Hyrich: None. A. Morgan: None. G. Wilson: None. D. Plant: None. J. Bowes: None. A. Barton: None.
OA24 Predicting drug immunogenicity to tumour necrosis factor inhibitors in patients with rheumatoid arthritis
Authors: Alshehri Mohammed , Nair Nisha , Yap Chuan Fu ,   BRAGGSS, Isaacs John D , Hyrich Kimme , Morgan Ann W , Wilson Anthony G , Barton Anne , Plant Darren
Published: April 2022

Background/Aims

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that irreversibly damages synovial joints. Tumour necrosis factor inhibitors (TNFi) may be prescribed for patients with moderate to severe RA. However, approximately 40% of patients do not respond well to TNFi, with a lack of effectiveness underpinned by immunogenicity (development of anti-drug antibodies) in some patients. A recent well-powered study by Sazonovs et al. (2020) reported a strong genetic association between the HLA-DQA1 locus and immunogenicity to TNFi in a cohort of Crohn's disease patients treated with either infliximab or adalimumab. The current study aimed to investigate the association between HLA alleles, primarily HLA-DQA1, and immunogenicity to adalimumab in RA patients.

Methods

Anti-adalimumab antibody titres were measured using radioimmunoassay in serum samples from RA patients following six months of treatment. Genetic datasets were generated using the Illumina OmniExpress genotyping array and, following standard quality control filtering, variants were imputed using SNP2HLA statistical software. Following imputation, filtering was performed to exclude variants in linkage disequilibrium or with low minor allele frequency. Logistic regression models were developed to explore the association between HLA alleles and amino acids and immunogenicity (all models were adjusted for sex). Amino acid positions of interest were annotated using P2Rank; a ligand binding site prediction tool.

Results

A total of 171 HLA alleles and 339 amino acid positions were analysed in 226 RA patients. The strongest association observed between HLA alleles and immunogenicity was for HLA-DQB1*02 (coefficient = 0.87; 95% CI, 0.31-1.43; p value = 2.10E-3), followed by HLA-DQA1*05 (coefficient = 0.91; 95% CI, 0.29-1.53; p value = 3.95E-3). The strongest associated amino acid positions were amino acids 66 and 67 within the ligand binding domain of the HLA-DQB1 protein.

Conclusion

In keeping with previous findings in Crohn's disease, variants within HLA-DQ molecules confer the strongest evidence for immunogenicity risk in RA patients receiving adalimumab. RA patients carrying these variants could be redirected to receive etanercept, an effective alternative to monoclonal antibodies that is not immunogenic. Further well-powered studies in RA are now warranted to replicate these findings.

Disclosure

M. Alshehri: None. N. Nair: None. C. Yap: None. J.D. Isaacs: None. K. Hyrich: Honoraria; Abbvie. A.W. Morgan: None. A.G. Wilson: None. A. Barton: None. D. Plant: None.
OA31 Youth-led development of an animated film to aid recruitment to a national youth advisory group for adolescent and young adult rheumatology
Authors: Lunt Laura E , Purvis Morgan , Gnanenthiran Suruthi , Zing Pelin , McDonagh Janet E , Rheum Your ,   a national advisory group of BANNAR
Published: April 2022

Background/Aims

Your Rheum is a national youth advisory group for adolescent and young adult rheumatology, to ensure meaningful involvement of young people at all stages of research. It was established in 2016 as a result of nationwide research, which reported that young people with rheumatic conditions wanted to be actively involved and had clear opinions of how they wanted to be involved and the priorities for such research. Young people ageing-out of the group remains challenging in view of the national nature of the group and was further compounded by the impact of the COVID-19 pandemic, which prevented the face-to-face meetings of the group. The aim of this project was to develop a short animation detailing what Your Rheum is about to encourage young people to join.

Methods

Content for the animation was gathered at a virtual Your Rheum meeting and via an online survey sent to members. A smaller group of members (n = 4) then worked with the Your Rheum facilitator and a national animation company, More Than Minutes, to create a script, storyboard, to choose imagery, colour schemes and discuss a voiceover. The animation was subsequently revised in the light of feedback from the young people.

Results

Key areas of content included: who can get involved in Your Rheum and membership; the different ways the group works with researchers for example group virtual and face-to-face activities, individual online activities; examples of different projects and topics of research discussed; why it is important to involve young people in research; how to contact the Your Rheum team. It was important to ensure the animation imagery was bright, fun and highlighted diversity. Language used in the film had to be clear and simple to understand, to enable young people from the age of 11 years upwards to relate. Subtitles on the video were also an important feature. The animation was successfully launched in September 2021 - [https://youtu.be/Y8OqmEJZ9Eo]

Conclusion

It is important to harness the experience and opinions of young people at all stages of research including recruitment strategies and dissemination, as this can result in resources that truly resonant with this age group.

Disclosure

L.E. Lunt: None. M. Purvis: None. S. Gnanenthiran: None. P. Zing: None. J.E. McDonagh: Consultancies; Consultancy fees from Pfizer (2018) and CSL-Behring (2021).
P050 Rapidly worsening subcutaneous oedema in a young boy: a case of juvenile dermatomyositis
Authors: Janagan Shalini , Udeshika W. A. E , Samarasinghe Pasindu M , Jagoda Jayatri D
Published: April 2022

Background/Aims

Juvenile onset dermatomyositis (JDM) is a rare disease with an incidence of 2-4 per million. The presentation includes skin manifestations of heliotrope rash, Gottron's papules, nail fold changes, bilateral peri-orbital or upper eyelid edema and focal mild facial swelling with muscle weakness. Widespread and generalized subcutaneous oedema is a rare presentation in JDM.

Methods

A 4-year-old previously healthy boy presented to a tertiary care hospital in Sri Lanka with generalized rash involving the face, limbs and trunk for seven days associated with facial puffiness and hair loss. He also complained of generalized myalgia and irritability and refused to walk. He did not have dysphagia, dysphonia or shortness of breath. He had a prodromal febrile illness two weeks back that had been treated as a viral fever. He had evidence of palatal ulcers, chelitis, malar rash, erythema of eyelids, eyelid swelling and necrotic vasculitic lesions in peripheries. He had tenderness over his thighs with muscle power being MRC grade 3/5 in the proximal muscles of his lower limbs. Arm and neck flexors’ power was normal.

Results

His ESR was raised at 35 mm/hour and CRP was normal. His CPK was 2726 U/l, AST was raised at 931 U/l, ALT was 511 U/l and albumin was 33 g/l. His ANA, dsDNA and ENA panel was negative. A myositis immunoblot could not be done due to financial constraints. An EMG showed evidence of myositis in his proximal muscles. He fulfilled the criteria for juvenile dermatomyositis based on Bohan and Peter’s criteria. He was treated with high dose steroids, dexamethasone 2 mg 6 hourly. While receiving steroids he deteriorated with worsening subcutaneous oedema of face and neck with high fever spikes. The oedema progressed to involve his whole body. His muscle power deteriorated with involvement of his arms. A venogram ruled out any obstructive venous disease. A CT CAP ruled out any underlying malignancy. His 2D echo revealed normal heart function. He was converted to IV Methylprednisolone 30 mg/kg and was started on plasmapharesis. He improved after the 3rd cycle and was started on cyclophosphamide infusions. He received six cyclophosphamide pulses with a tapering course of steroids. He remains controlled in his disease with no new muscle weakness or skin manifestations. However, he remains steroid dependent and is awaiting treatment with Rituximab.

Conclusion

Subcutaneous oedema in JDM is attributed to a vasculopathy. This is associated with severe rapidly progresssive disease with high mortality and requires aggressive immunosuppression. As seen in our patient disease is resistant to conventional treatment. Early recognition leads to better outcomes in these patients.

Disclosure

S. Janagan: None. W.A.E. Udeshika: None. P.M. Samarasinghe: None. J.D. Jagoda: None.
P098 Estimating the prevalence and predictors of musculoskeletal disability in Tanzania: a pilot study
Authors: Yongolo Nateiya M , Bunn Christopher , Halliday Jo , Mtesha Benson , Kelly Clive , Mwingwa Anthon , Biswaro Sanjura , Siebert Stefan , Hemed Asia , Walker Richard , McIntosh Emma , Mmbaga Blandina
Published: April 2022

Background/Aims

Musculoskeletal (MSK) disorders are among the major causes of disability worldwide, accounting for 20% of all years lived with disability. MSK disorders are linked to other non-communicable diseases (NCDs) as their adverse impact on mobility may promote the development of other NCDs. Prevalence studies of MSK disorders in Africa are limited with most coming from South Africa, while none have been previously performed in Tanzania. Screening for MSK disorders is not routinely conducted in health care facilities and there are no registered consultants working in this field in Tanzania. This pilot study aimed to provide an initial estimate of the prevalence and predictors of MSK disability to inform the design of a more detailed study of MSK disorders in Tanzania.

Methods

A cross-sectional pilot study was conducted in Kirima village, Hai District, Kilimanjaro region which has a total population of 1,911 people. We obtained ethical approval to invite each eligible individual to consent to supervised examination using the Gait, Arms, Legs and Spine (GALS) assessment tool (adults aged 18 years and over) or the paediatric GALS (pGALS) assessment tool (children aged 5 to 17 years old). In those where these screening tools detected an abnormality, we then performed a full Regional Examination of Musculoskeletal System (REMS). We also assessed functional status and physical disability in all GALS positive subjects using the Modified Health Assessment Questionnaire (MHAQ) tool. All adults were assessed during planned accompanied household visits, while a substantial number of the children were assessed while at school. Multivariable logistic regression analyses were carried out to assess the influence of demographic variables on GALS, REMS and MHAQ outcomes.

Results

A substantial number of adults (270) and children (491) could not be contacted or declined to consent to examination. Among the 1150 people who did consent, the prevalence of GALS/pGALS positivity was 8.2% (95% CI: 6.6-9.8), while REMS was positive in 3.5% (95% CI: 2.4-4.5). Female gender and increasing age were both significantly associated with each of GALS and REMS positivity. The MHAQ score was strongly associated with REMS positivity and significantly associated with GALS positivity, equating to worse function and greater disability.

Conclusion

These initial prevalence estimates and predictors of MSK disability are comparable to those seen elsewhere in the world. Greater detail on the prevalence of specific MSK disorders in Tanzania will require larger and more detailed studies.

Disclosure

N.M. Yongolo: None. C. Bunn: None. J. Halliday: None. B. Mtesha: None. C. Kelly: None. A. Mwingwa: None. S. Biswaro: None. S. Siebert: None. A. Hemed: None. R. Walker: None. E. McIntosh: None. B. Mmbaga: None.
P110 Adherence with mycophenolate mofetil in connective tissue disorders
Authors: Chauhan Aarti , Bunting Helen , Dubey Shirish
Published: April 2022

Background/Aims

Connective tissue disorders like systemic lupus erythematosus (SLE) are multi-organ systemic conditions characterised by disordered immune function. Mycophenolate mofetil (MMF) is commonly used for treatment of SLE and other connective tissue disorders. Compliance with drugs remains a significant issue in management of these conditions and varying reports from across the world continue to show significant lack of concordance resulting in increased disease activity and damage. The aim of this study was to investigate the adherence specifically with MMF treatment among patients attending clinics at University Hospitals Coventry and Warwickshire NHS Trust (UHCW)with SLE and other connective tissue disorders.

Methods

Ethical approval was obtained through research and development department within the Trust. This is a retrospective study collating non-identifiable hospital pharmacy data in patients who requested the prescription for MMF drug between January 2015 and December 2018. Clinical data were obtained from paper and electronic notes. Data were analysed using Microsoft Excel.

Results

We recruited 144 patients into this study with a wide age range from 18 to 91 years. Demographic data showed 100 out of 144 cases were females and 44 were males. There were 112 Caucasian patients, 22 of South Asian origin, 3 East Asian and 4 black patients. Of the 144 patients, SLE was the diagnosis for 56 patients and 88 patients had other diagnoses including scleroderma (18), mixed connective tissue disease (15), myositis (13), vasculitis (13) and Sjogren’s syndrome (10). Overall adherence with MMF was 68.3%. We found good adherence was seen in age group 41-60 years, tailing off in younger and older adults. The adherence rates were below 80% for all the age groups. Poor adherence with MMF correlated with 50% increase in risk of flares, with good adherence reducing the risk by 50% compared with overall risk of flares. We found a significant correlation between lack of compliance and risk of flares (r = 0.25, p < 0.002). We compared the results for 112 Caucasian patients and 25 Asian patients which included South Asian and South East Asian patients. This showed a significant difference with reduced adherence among Asian patients (mean adherence 48%) in comparison to Caucasian patients (mean adherence 65%, p = 0.0055). There were no differences between SLE and other CTDs. We also did not find any trends with organ involvement, specifically with neurological involvement.

Conclusion

Adherence with MMF has improved considerably compared to previous studies. However, challenges remain and certain population groups such as young adults, elderly and Asian patients continue to have low adherence levels. Alternative strategies are needed to improve their health and reduce risk of flares and organ damage.

Disclosure

A. Chauhan: None. H. Bunting: None. S. Dubey: Honoraria; Lilly, Abbvie. Member of speakers’ bureau; Janssen.
P176 Meeting the demands of employment: the impact and rehabilitation of chronic pain and fatigue in the UK armed forces
Authors: Chisala Elijah , Bahadur Sardar
Published: April 2022

Background/Aims

The growing prevalence of chronic pain and the recent influx of post-viral fatigue (due to COVID-19) will limit the working output of the UK population. As such presentations become more common, the ability of the working population to meet the demands of their employment will depend on the effective management of chronic pain and fatigue.

We investigated the working ability and outcomes of UK military personnel two years after rehabilitation for persistent pain or fatigue.

Methods

We collected the health data of 35 personnel presenting with primary persistent pain, fibromyalgia, or persistent fatigue during admission to the 2-week Specialist Rehabilitation Course at DMRC between November 2018 to December 2019. Participants scored their current ability to work and the work-related impact of their symptoms by completing a follow-up survey. This group also evaluated the efficacy of 14 evidence-based rehabilitation tools provided during their rehabilitation programme based on how they improved their ability to work.

Results

88.2% of attendees had a history of mental health issues, whilst 82.4% had other medical comorbidities. Royal Air Force (RAF) personnel predominantly presented with fatigue rather than pain; this subgroup left the armed forces two years earlier than the service average. 62.9% of attendees responded to our survey. 63.6% of respondents no longer served in the military two years after their initial admission to the rehabilitation course. All current military personnel reported either “good” or “very good” symptom management and as a cohort reported better work outcomes than those who had left the military. Respondents reported mindfulness, activity pacing and education about symptoms as the most effective strategies for improving work capability. Those who found these strategies most useful had the best outcomes. 7 of the 8 retained military personnel found at least two of these strategies useful for improving their work ability compared to 4 of the 14 military leavers.

Conclusion

Poor working ability due to persistent pain or fatigue was not compatible with sustained military employment. Yet, the tools provided at DMRC improved the ability to work for those remaining in the military. Military personnel with persistent pain and fatigue benefitted most from mindfulness, activity pacing and education. Response to these specific strategies corresponded with both continued military service and better work capabilities. These findings are consistent with the recent literature regarding the efficacy of these rehabilitation strategies for persistent pain and fatigue. The occupational outcomes of military personnel in this study may be comparable to that of civilian populations; specifically sectors with similar demands or mental health risks as the armed forces.

Disclosure

E. Chisala: None. S. Bahadur: None.
P232 In the absence of idiopathic inflammatory myopathy, is the presence of anti-transcriptional intermediary factor-1 gamma clinically relevant for malignancy?
Authors: Cotton Caroline V , Keymer Catherine , McLaren Zoe
Published: April 2022

Background/Aims

The idiopathic inflammatory myopathies (IIMs) are associated with a number of antibodies which are linked to certain clinical phenotypes. The presence of anti-transcriptional intermediary factor-1 gamma (TIF-1y) is strongly associated with malignancy. However, it is uncertain whether the presence of this antibody, in the absence of IIM, should prompt further investigations to exclude an underlying malignancy.

Methods

Patients were identified who had undergone myositis immunoblot testing at Liverpool University Foundation Trust laboratories as part of their clinical care between January 2015 and January 2020. Adult patients were included if they tested TIF-1y antibody positive but had no evidence of IIM. Data was collected on patient demographics, whether this was a weak or strong antibody finding and whether there was the presence of other antibodies on the immunoblot panel. The clinical notes were then used to assess whether the patient was known to have a malignancy or went on to develop a malignancy during the follow up period.

Results

The presence of TIF-1y antibody occurred in 66 patients. Four patients were excluded from analysis, three due to a diagnosis of IIM and one due to a lack of clinical information. The average age was 69 years (range 35 - 88 years) and 59% were female. A strongly positive TIF-1y antibody was found in 19 patients, of which eight were associated with another positive antibody available on the immunoblot panel. There were five malignancies identified, two were historic diagnoses, one patient was found to have a lung malignancy at the time the panel was sent and two patients subsequently developed pancreatic malignancy. A weakly positive TIF-1y antibody was found in 43 patients, of which 16 results were associated with another positive antibody on immunoblot analysis, excluding three patients with a positive anti-Ro antibody. Of 11 patients with malignancy, five had a historic diagnosis and six patients developed malignancy over the follow up period.

Conclusion

The myositis immunoblot is a useful tool in patients with IIM. However, when used outside of this context can produce a number of positive results, the significance of which are unclear. In the case of TIF-1y and its known association with malignancy, this can lead to unnecessary investigations and increase patient anxiety. This data has obvious limitations as there may have been incomplete information if patients were managed elsewhere and the presence of TIF-1y did not lead to investigation for underlying malignancy in the majority of patients, meaning some cancers may have been present but remained undetected. The results do not suggest the presence of this antibody increases the likelihood of malignancy in patients without IIM but further studies are recommended.

Disclosure

C.V. Cotton: None. C. Keymer: None. Z. McLaren: None.
P242 Immunosuppressants can modify the transcriptomic signature in patients with systemic lupus erythematosus
Authors: Akthar Mumina , Nair Nisha ,   on behalf of the MASTERPLANS Consortium and BILAG BR Investigators, Bruce Ian N , Reynolds John A
Published: April 2022

Background/Aims

Transcriptomics has the potential to revolutionise the way we approach complex diseases such as systemic lupus erythematosus (SLE), which is both clinically and biologically heterogeneous. We aimed to explore whether deconvolution of whole blood transcriptomic data could predict differences in immune cell proportions between active SLE patients, and whether these are attributable to the SLE phenotype or medication use.

Methods

Patients with active SLE were recruited from the BILAG-Biologics Registry (BILAG-BR) prior to change in therapy. Disease activity was measured using the BILAG-2004 Index. Whole blood RNA-sequencing was conducted at baseline and FPKM-normalised data was deconvoluted using CIBERSORTx with the LM22 signature matrix used as reference. The effects of five different drugs (azathioprine, cyclophosphamide, hydroxychloroquine, methotrexate and mycophenolate mofetil [MMF]) were explored. Predicted cell frequencies were compared between active disease domains (defined by BILAG A or B score) and concomitant immunosuppressant use using Mann-Whitney U tests with Benjamini-Hochberg correction (significance at p < 0.05).

Results

We recruited 109 patients of whom 104 (95.4%) were female, with a median (IQR) age of 38 years (29-49) years, disease duration of 10 (6.5, 16.5) years. Patients had active disease with a median SLEDAI score of 8 (4-14). For patients taking MMF (53/109, 46.8%), there was a lower proportion of macrophages M0 (0.435% vs 1.391%, p = 0.001), naïve CD4 T cells (0.961% vs 2.251%, p = 0.002) and regulatory T cells (1.858% vs 3.574%, p = 0.007), and a higher proportion of memory activated CD4 T cells (1.826% vs 1.113%, p = 0.015), when compared to patients not taking mycophenolate mofetil. MMF use was associated with statistically significant differences in predicted immune cell (macrophages m0, naïve CD4 T cells, regulatory T cells and memory activated CD4 T cells) frequency after adjusting for age, gender, ethnicity, disease duration, renal disease and steroid use. No differences were observed for the other immunosuppressants or between patients with active or inactive disease in each of the nine organ domains.

Conclusion

The use of immunosuppressants can significantly modify the transcriptomic signature in patients with SLE affecting key immune cell type populations differently, highlighting the need to adjust for background medication use in future studies, particularly in those using whole blood transcriptomics. It would also be valuable to evaluate the differences identified in this study to determine whether they can be used to monitor or predict treatment response.

Disclosure

M. Akthar: None. N. Nair: None. O. MASTERPLANS Consortium and BILAG BR Investigators: None. I.N. Bruce: None. J.A. Reynolds: None.
Safety of DIEP Flap Reconstruction in Patients with Factor V Leiden: A Retrospective Cohort Study
Authors: Veeramani Anamika , McCarty Justin C. , Vieira Brittany L. , Karinja Sarah , Pusic Andrea L. , Carty Matthew J. , Erdmann-Sager Jessica
Published: April 2022

Background:

Factor V Leiden (FVL) is the most common inherited thrombophilia in White people. Thrombotic complications resulting from free flap breast reconstruction in FVL patients have been studied to a limited degree. We evaluated whether patients heterozygous for a FVL mutation undergoing deep inferior epigastric perforator flap reconstruction had increased risk of micro- or macrovascular thrombotic complications compared with patients without a diagnosed thrombophilia.

Methods:

We performed a retrospective cohort study of deep inferior epigastric perforator flap reconstructions at Brigham and Women’s Hospital (1/2015–12/2020) comparing patients diagnosed as FVL heterozygotes compared with matched controls without a diagnosed thrombophilia. Patients were matched using coarsened exact matching algorithm based on clinical characteristics. The primary outcomes were micro- (return to OR for flap compromise, flap loss) and macrovascular (venous thromboembolism) complications.

Results:

A total of 506 patients (812 flaps) were included in this study. Eleven patients (17 flaps) were FVL heterozygotes. After matching, 10 patients (16 flaps) with FVL were matched to 55 patients (94 flaps). The return to OR for flap compromise was 0% in the FVL cohort compared with 5% (n = 5/94, 3/94 flaps lost, P = 1.00) in the matched controls (1.9%, n = 15/795 in unmatched controls, 0.6%, n = 5/795 loss rate). There were zero venous thromboembolism events among FVL patients compared with 2% of controls (n = 1/55).

Conclusions:

FVL heterozygosity did not increase the risk of micro- or macrovascular complications in patients undergoing deep inferior epigastric perforator flap breast reconstruction. This study supports the safety of microvascular reconstruction in this group of patients when appropriate venous thromboembolism prophylaxis is given.
Use of Needle Localization in the Surgical Management of Non-seroma, Mass-forming BIA-ALCL
Authors: Kim David H. , Webster Theresa K. , Bartolacci Joseph G. , Araya Sthefano , Panichella Juliet , Patel Sameer A.
Published: April 2022

Outcomes related to the treatment of breast implant-associated anaplastic large cell lymphoma, a rare extranodal T-cell lymphoma associated with textured breast implants, are largely dependent on the successful resection to negative margins via en bloc capsulectomy and resection of any associated masses. To date, the use of needle localization, a common technique used in breast surgery, to assist in the complete removal of breast implant-associated anaplastic large cell lymphoma has not been described. We present the case report of a 66-year-old woman, with a previous medical history of left-sided invasive ductal carcinoma, who presented 7 years after textured breast implant placement with a left-sided mass without peri-implant seroma. Biopsy demonstrated breast implant-associated anaplastic large cell lymphoma and the associated breast mass extended beyond the capsule borders. The present report describes the novel use of needle localization in this patient to facilitate the complete removal of the malignancy-associated mass with maximal preservation of the overlying soft tissue envelope.
Acute Onset Endophthalmitis Following Bilateral Upper and Lower Eyelid Blepharoplasty
Authors: Venincasa Michael J. , Shoji Marissa K. , Al-Khersan Hasenin , Maeng Michelle M. , Johnson Thomas E. , Flynn Harry W.
Published: April 2022

A 59-year-old woman presented with iritis and uveitis in the OD approximately 3 weeks after she underwent a bilateral upper and lower blepharoplasty by an outside oculoplastic specialist. Examination revealed a visual acuity of hand motion in the OD, scleral ulceration suspicious for prior globe perforation, dense vitritis, and loculations and membranes on echography. The patient was diagnosed with acute onset exogenous endophthalmitis. Vitreous aspiration and intravitreal injection of vancomycin and ceftazidime were performed. The patient underwent a pars plana vitrectomy, and vitreous culture demonstrated Streptococcus pseudoporcinus. Postoperative vision improved to 4/200 but was limited by a full-thickness macular hole. Despite silicone oil removal and macular hole repair, the macular hole remained open at month 7 and limited vision to 5/200. During eyelid surgery, surgeons should take precautions against intraoperative needle perforation including possible use of protective shield. Postoperative vision loss after eyelid surgery requires further evaluation.
Treatment of Orbital Desmoid-type Fibromatosis With Sorafenib
Authors: Downie Elaine M. , Amend Christina E. , Miranda Alexander , Burkat Cat N.
Published: April 2022

Desmoid-type fibromatosis is a rare tumor, particularly in the orbit, with fewer than 10 cases of primary orbital desmoid-type fibromatosis reported in the literature. The authors present a case of an infant who presented with rapid onset of OD proptosis, disc edema, and hyperopic shift who was found to have a retrobulbar desmoid-type fibromatosis. After initial biopsy, due to risk of vision loss with complete excision, the tumor was treated with sorafenib, a tyrosine kinase inhibitor. During the course of treatment with sorafenib, the tumor stabilized and then regressed in size. To the authors’ knowledge, this is the first reported case of orbital desmoid-type fibromatosis to be treated with sorafenib.
CaV3.2 calcium channels contribute to trigeminal neuralgia
Authors: Gambeta Eder , Gandini Maria A. , Souza Ivana A. , Zamponi Gerald W.
Published: April 2022

Trigeminal neuralgia (TN) is a rare but debilitating disorder characterized by excruciating facial pain, with a higher incidence in women. Recent studies demonstrated that TN patients present mutations in the gene encoding the CaV3.2 T-type calcium channel, an important player in peripheral pain pathways. We characterize the role of CaV3.2 channels in TN at 2 levels. First, we examined the biophysical properties of CACNA1H variants found in TN patients. Second, we investigated the role of CaV3.2 in an animal model of trigeminal neuropathic pain. Whole-cell patch-clamp recordings from 4 different mutants expressed in tsA-201 cells (E286K in the pore loop of domain I, H526Y, G563R, and P566T in the domain I-II linker) identified a loss of function in activation in the E286K mutation and gain of function in the G563R and P566T mutations. Moreover, a loss of function in inactivation was observed with the E286K and H526Y mutations. Cell surface biotinylation revealed no difference in channel trafficking among the variants. The G563R mutant also caused a gain of function in the firing properties of transfected trigeminal ganglion neurons. In female and male mice, constriction of the infraorbital nerve induced facial thermal heat hyperalgesia. Block of T-type channels with Z944 resulted in antihyperalgesia. The effect of Z944 was absent in CaV3.2−/− mice, indicating that CaV3.2 is the molecular target of the antihyperalgesic Z944 effect. Finally, enzyme-linked immunosorbent assay analysis revealed increased CaV3.2 channel expression in the spinal trigeminal subnucleus caudalis. Altogether, the present study demonstrates an important role of CaV3.2 channels in trigeminal pain.
Nursing Care Experiences With Syrian Refugees in Southern Turkey: A Metaphor Analysis
Authors: AKGÜL-GÜNDOĞDU Nurcan , TAŞ Filiz , SELÇUK-TOSUN Alime
Published: April 2022

Background

Healthcare professionals' “cultural prejudices” toward individuals' cultural beliefs, attitudes, and perceptions affect the care they provide. Their awareness of their bias is closely associated with the quality of healthcare provided.

Purpose

This study was designed to assess nurses' perceptions regarding providing care to Syrian refugee patients using metaphors and to evaluate their views based on these metaphors.

Methods

The participants in this qualitative study consisted of 80 nurses who worked in Level 1 and Level 2 health institutions. Data were collected using an interview form prepared by the researchers. The form included descriptive characteristics of the nurses and two expressions used to determine the nurses' opinions on providing care for Syrian refugee patients. The nurses were given an incomplete sentence, which was “Providing care for a Syrian refugee patient…because…,” and were asked to complete the blanks. The data were analyzed using the content analysis method.

Results

On the basis of “providing care for Syrian refugee patients,” four categories of metaphors were determined: occupational awareness, health promotion, a difficult process/resistance, and providing service in vain. The participants generated 50 metaphors, with “humanity,” “a baby/little child,” and “a barrier” as the three most used metaphors, belonging to the “occupational awareness” and “a difficult process/resistance” categories, respectively.

Conclusions/Implications for Practice

The metaphors of nurses regarding giving care to Syrian refugee patients were mostly concentrated in the categories of “occupational awareness” and “a difficult process/resistance.” Metaphors generated by the nurses offer a powerful research tool to reveal, understand, and explain nurses' personal perceptions and to develop and support nursing care accordingly. In addition, the subject of transcultural nursing should be discussed more extensively in nursing education programs. Understanding the social context of refugees is very important during the nursing care process.
Academic Entitlement and Its Potential Educational Consequences: A Scoping Review
Authors: Kinne Bonni Lynn , Goehring Meri Tienn , Lee Williams Betsy
Published: April 2022

Background and Purpose.

In 2020, the first and only study to investigate academic entitlement in doctor of physical therapy (DPT) students was published. In the review of literature section of the study, the authors alluded to the premise that academic entitlement seems to be directly related to several educational consequences. The purpose of this scoping review was to determine what educational consequences may result from increased academic entitlement, especially as they relate to DPT students.

Methods.

A scoping review was conducted to systematically identify what is known about the correlation between academic entitlement and its educational consequences. The scoping review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist.

Results.

A total of 25 studies were included in the scoping review. For ease of interpretation, the authors organized the statistically significant findings into content areas composed of learning processes related to academic confidence, learning processes related to academic preferences, learning outcomes related to self, and learning outcomes related to others.

Discussion and Conclusion.

This scoping review determined that several educational consequences may result from increased academic entitlement. A few of the educational factors related to increased academic entitlement also led to adverse personal consequences for both students and their faculty members. Future research should include a review that determines all the possible causes of increased academic entitlement. This information would be beneficial to instructors involved in all levels of education, including faculty members employed in a DPT program.
Endoscopic Submucosal Dissection (ESD) Offers a Safer and More Cost-effective Alternative to Transanal Endoscopic Microsurgery (TEM)
Authors: Kim Marina , Bareket Romy , Eleftheriadis Nikolas P. , Kedia Prashant , Seewald Stefan , Groth Stefan , Nieto Jose , Kumta Nikhil A. , Deshmukh Ameya A. , Katz Jordan , Suresh Supriya , Zamarripa Felipe , Martínez Ma Guadalupe , Liu-Burdowski Jennifer , Gaidhane Monica , Sarkar Avik , Shahid Haroon M. , Tyberg Amy , Kahaleh Michel
Published: April 2022

Background:

Endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) are minimally invasive procedures that treat early rectal cancer (ERC). Both are effective treatments, yet there are very few studies comparing them. The aim of our study was to identify ideal candidates for each procedure.

Materials and Methods:

Between January 2016 and November 2019, 204 ERC patients were managed with either ESD (n=101) or TEM (n=103) at 7 international centers. Data analyzed included clinical success, tumor characteristics, procedure info, and recurrence rates.

Results:

Median tumor size was 40 mm±23.9 in the ESD group and 56 mm±27.9 in the TEM group, significantly larger in the latter (P<0.00001). Average procedure time was 131.5±67.9 minutes in ESD group and 104.9±28.4 minutes in TEM group (P=0.000347). Average hospital stay was 3.3±2.6 days in the ESD group and 4.7±0.7 days in the TEM group (P<0.00001). Adverse event rate was 6.8% in the ESD group and 24% in the TEM group. There were no significant difference in the rate of en bloc resection, technical success, tumor location, necessity of additional procedures, and tumor recurrence rates.

Conclusion:

Compared with TEM, ESD is a safer procedure with shorter hospital stay and should be offered for patients who have ERC.
A Narrative Review of Pediatric Respite Care Initiatives in the United States
Authors: Ferragamo Tara , Pituch Kenneth J. , Sorkin Tsovinar , Simon Natalia , Lindley Lisa C. , Weaver Meaghann S.
Published: April 2022

Families of children receiving palliative care depict lack of respite services as a top unmet need. Although the benefits of access to respite services are notable, little is known on a state-by-state basis about respite provision or funding. The study objective was to conduct a national evaluation of pediatric respite care programs to identify and describe how states provide and fund respite care for children. The study approach adhered to the Scale for the Assessment of Narrative Review Articles quality standards using multiple data sources including engagement with the existing literature, content analyses of public-facing websites, and conversations with 40 stakeholders from 15 states. States offered respite services in a variety of ways: Medicaid waivers used to fund respite care, state-funded programs that provide respite, and philanthropy-based respite facilities. This narrative review revealed the creativity involved in different settings to improve respite access, staffing, and reimbursement. Suggestions to address the unmet respite needs of families included establishing a respite home, improving Medicaid reimbursement, expanding Medicaid waiver eligibility, providing a respite benefit through Medicaid, implementing nursing workforce initiatives, and centralizing staffing databases.