bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of post cardiac surgery acute myocardial infarction and role of emergency percutaneous coronary interventions
Authors: Laimoud M , Qureshi R
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The rapid haemodynamics deterioration and  presence of myocardial ischemia  early  after cardiac surgical operations is a complex life threatening condition  where rapid diagnosis and management is of fundamental importance. Objective: to  analyse the factors associated with mortality of patients with post cardiotomy MI  and  to study the role of emergency coronary angiography in management and outcome . Methods: we retrospectively enrolled  adult patients  diagnosed to have post cardiotomy MI and underwent emergency coronary angiography  at our tertiary care hospital  between January 2016 and August 2019. Results: Sixty one patients from consecutive  1869 adult patients who underwent cardiac surgeries were enrolled in our study.  The studied patients had a mean age of 49 ±16.2 years with a mean BMI of 29.5 ± 6.6 and 65.6% of them were males. As compared to the survivors group, the non-survivors of perioperative MI had significant preoperative CKD , postoperative AKI , longer CPB time , frequent  histories of  previous PCI , previous cardiotomies , pre and postoperative ECMO use , higher median troponin I levels , higher peak and 24 hours mean lactate levels. Regression analysis revealed that re-operation for revascularization  (OR:23 ; 95% CI: 8.27-217.06; p = 0.034) and hyperlactataemia  (OR: 3.21 ; 95% CI:1.14-9.04 ; p = 0.027) were independent factors associated with hospital mortality after perioperative MI . Hospital mortality occurred in ( 25.7% vs 86.7% ,p < 0.001 ) , AKI occurred in ( 37.1% vs 93.3 %,p < 0.001 ) , haemodialysis was used in (28.6 % vs 80%. P = 0.002), mediastinal exploration for bleeding done in (31.4% vs 80%, p = 0.006 ) in PCI and re-operation groups respectively while there were no significant differences regarding gastrointestinal bleeding , cerebral strokes nor intracerebral bleeding . Absence of significant angiographic findings occurred in 18% of patients. Conclusions: Perioperative MI is associated with significant morbidities and hospital mortality . Re-operation for revascularization  and progressive hyperlactataemia are independent predictors of hospital mortality. Emergency coronary angiography is helpful in diagnosis and management of perioperative MI. Predictors of hospital mortality.Significant variablesP valueOR95% CIPost-op ECMO0.1360.0390.001 -2.775Troponin0.6611.0000.998 -1.001Lactate peak0.0273.2121.141 - 9.042Re-operation0.03423.0058.27 - 217.06Abstract Figure. Hospital outcomes of PCI and Reoperation
Surgical and endovascular treatment of adult aortic coarctation : tewenty years experience center
Authors: Ben Mabrouk J , Mleyhi S , Ziadi J , Boudiche S , Miri R , Farhati A , Ben Mrad M , Mourali S , Denguir R
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Aortic coarctation accounts for 5 to 8 % of the congenital heart diseases.  In adult patients, an expected mortality of 75 % at 43 years old was reported.

conventional surgery was the gold standard in the treatment of these patients. Currently with the advancement of endovascular procedures, angioplasty with ou no stenting is increasingly indicated.

Methods

We report a retrospective, monocentric observational study of 57 patients treated for aortic coarctation surgically or by endovascular approach over a period of 20 years, from 2000 until 2020.

Results

The median age was 22 years with extremes of 15 and 65 years and the sex ratio was 1.42. All patients were hypertensive. The median of the trans-stenotic gradient was 60 mmHg. Surgical repair consisted mainly of resection-anastomosis using the Crafoord technique in 25 patients (44%) and interposition of a Dacron tube in 22 patients (39%). Endovascular treatment with stenting was done in seven patients.

Post treatment gradient was 10 mm Hg ± 5 and no deaths were observed at 30 days. After an average follow-up of 70 months, residual hypertension was found in seven cases without any re-coarctation and in the univariate analysis, the main factors significantly associated with this residual  hypertension were: age (p = 0.11), pre and post-operative gradient (p = 0.097), severe hypertension (p = 0,12), developed collateral circulation (p = 0.07), bicuspid aortic valve (p = 0.15) and diaphragm shape (p = 0.07).

Conclusion

The gold standard treatment remains the surgical correction but in selected patients, the endo-vascular repair is a valid option.we propose a decision-making algorithm based on the results of our study (Fig) Abstract Figure. decision-making algorithm
Adherence to recommendations for secondary prevention medications after myocardial infarction in Estonia
Authors: Loiveke P , Marandi T , Ainla T , Fischer K , Eha J
Published: April 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Estonian Research Council

Introduction

High rates of adherence to myocardial infarction (MI) secondary prevention medications have been reported by several studies in Europe.  However, results derived from unselected populations registry based data is scarce.

Purpose

Aim of our study was to analyse adherence to guideline recommended medications for secondary prevention of MI of unselected patient population in Estonia in 2017-2018 and compare the results with data from 2004-2005.

Methods

Population studied in 2004-2005 was based on Estonian Health Insurance Fund"s (EHIF) database and in 2017-2018 on Estonian Myocardial Infarction Registry (EMIR). EMIR is an ongoing registry recording data from all patients in Estonia diagnosed with MI (ICD-10 I21 – I22). Patients hospitalised due to MI and survived > 30 days formed the study population. By linking to EHIF"s prescription database medication adherence for angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), statins, beta blockers (BB) and P2Y12 inhibitors clopidogrel and ticagrelor was assessed during one year follow-up period from first hospitalisation during period studied (at least one reimbursed prescription for the drug group during follow-up period).

Results

4900 and 5067 index episodes were defined in 2004-2005 and 2017-2018, respectively. Mean age in the study population was 64.7 (+/- 11.5) and 66.5 (+/- 12.1) for men and 72.7 +/- 9.9 and 76.4 +/- 10.9 for women in 2004-2005 and 2017-2018. Rates of medication adherence among patients who survived > 30 days are presented in the Table.

Conclusion

Adherence to guideline recommended medication for secondary prevention of MI in Estonia has improved considerably over 13 years. Based on our data there is room for advancement, especially among women and the elderly. Rates of medication adherence.2004-20052017-2018p value (comparison between studies)MEN (n = 2365)WOMEN (n = 1660)TOTAL (n = 4025)MEN (n = 2704)WOMEN (n = 1668)TOTAL (n = 4372)BB, No. (%)1907 (80.6)1344 (81.0)3251 (81.0)2265 (84.0)1385 (83.0)3650 (83.5)0.001ACE/ARB, No. (%)1780 (75.3)1317 (79.3)3097 (76.9)1817 (67.2)1070 (64.1)2887 (66.0)< 0.001Statins, No. (%)946 (40.0)826 (50.0)*1772 (44.0)1910 (70.6)1020 (61.2)*2930 (67.0)< 0.001Statin + ACE/ARB + BB, No. (%)999 (42.2)647 (39.0)1646 (40.9)1336 (49.4)686 (41.1)*2022 (46.2)< 0.001None of the above medications, No. (%)130 (5.5)96 (6.0)226 (5.6)214 (7.9)148 (9.0)362 (8.3)< 0.001P2Y12 inhibitorsNANANA2194 (81.1)1147 (69.0)*3341 (76.4)NABB, beta-blockers; ACE/ARB, angiotensin converting enzyme inhibitors/angiotensin II receptor blockers. NA, not available *P < 0.01 for comparison between men and women with Pearson"s χ2 test. Pearson"s χ2 test used for comparison between studies.
Identification and characterization of rapidly accumulatingsch9Δsuppressor mutations inSaccharomyces cerevisiae
Authors: Peterson Patricia P , Liu Zhengchang
Published: April 2021

Nutrient sensing is important for cell growth, aging, and longevity. In Saccharomyces cerevisiae, Sch9, an AGC-family protein kinase, is a major nutrient sensing kinase homologous to mammalian Akt and S6 kinase. Sch9 integrates environmental cues with cell growth by functioning downstream of TORC1 and in parallel with the Ras/PKA pathway. Mutations in SCH9 lead to reduced cell growth in dextrose medium; however, reports on the ability of sch9Δ mutants to utilize non-fermentable carbon sources are inconsistent. Here, we show that sch9Δ mutant strains cannot grow on non-fermentable carbon sources and rapidly accumulate suppressor mutations, which reverse growth defects of sch9Δ mutants. sch9Δ induces gene expression of three transcription factors required for utilization of non-fermentable carbon sources, Cat8, Adr1, and Hap4, while sch9Δ suppressor mutations, termed sns1 and sns2, strongly decrease the gene expression of those transcription factors. Despite the genetic suppression interactions, both sch9Δ and sns1 (or sns2) homozygous mutants have severe defects in meiosis. By screening mutants defective in sporulation, we identified additional sch9Δ suppressor mutants with mutations in GPB1, GPB2, and MCK1. Using library complementation and genetic analysis, we identified SNS1 and SNS2 to be IRA2 and IRA1, respectively. Furthermore, we discovered that lifespan extension in sch9Δ mutants is dependent on IRA2 and that PKA inactivation greatly increases basal expression of CAT8, ADR1, and HAP4. Our results demonstrate that sch9Δ leads to complete loss of growth on non-fermentable carbon sources and mutations in MCK1 or genes encoding negative regulators of the Ras/PKA pathway reverse sch9Δ mutant phenotypes.
A Chromosome—Level Genome Assembly of the Spotted Scat (Scatophagus argus)
Authors: Huang Yuanqing , Mustapha Umar Farouk , Huang Yang , Tian Changxu , Yang Wei , Chen Huapu , Deng Siping , Zhu Chunhua , Jiang Dongneng , Li Guangli
Published: April 2021

The spotted scat, Scatophagus argus is a member of the family Scatophagidae found in Indo-Pacific coastal waters. It is an emerging commercial aquaculture species, particularly in East and Southeast Asia. In this study, the first chromosome-level genome of S. argus was constructed using PacBio and Hi-C sequencing technologies. The genome is 572.42 Mb, with a scaffold N50 of 24.67 Mb. Using Hi-C data, 563.28 Mb (98.67% of the genome) sequences were anchored and oriented in 24 chromosomes, ranging from 12.57 Mb to 30.38 Mb. The assembly is of high integrity, containing 94.26% conserved single-copy orthologues, based on BUSCO analysis. A total of 24,256 protein-coding genes were predicted in the genome, and 96.30% of the predicted genes were functionally annotated. Evolutionary analysis showed that S. argus diverged from the common ancestor of Japanese puffer (Takifugu rubripes) approximately 114.8 Ma. The chromosomes of S. argus showed significant correlation to T. rubripes chromosomes. A comparative genomic analysis identified 49 unique and 90 expanded gene families. These genomic resources provide a solid foundation for functional genomics studies to decipher the economic traits of this species.
De-objectifying Animals
Authors: Lostal Marina
Published: April 2021

The legal framework of the International Criminal Court does not contain any provision concerning animals. This stands in contrast with the frequency with which they appear in both trial and reparations proceedings. The silence of the legal framework is problematic insofar as the ‘animal turn movement’, which questions the classical understanding and treatment of animals as objects, has permeated into both the international and domestic legal spheres. This article wishes to initiate a discussion on the treatment of animals before the Court by examining whether they could qualify as victims under Rule 85(a) of the Rules of Procedure and Evidence. While the short answer to this question is an unequivocal ‘no’, the conclusion reached is not the purpose of the analysis. The analysis shows that animals cannot qualify as ‘victims’ because they are not human beings. Yet, they comfortably meet the other two criteria, namely, (a) suffering harm, which (b) results from the commission of crimes within the Court’s jurisdiction. Thus, this article argues that — at least — granting animals the same treatment as human beings is no more objectionable as a matter of legal principle than granting them the status of ‘things’. This calls for a prompt discussion of the regulation of animals within the Court.
Combined statistical modeling enables accurate mining of circadian transcription
Authors: Rubio-Ponce Andrea , Ballesteros Iván , Quintana Juan A , Solanas Guiomar , Benitah Salvador A , Hidalgo Andrés , Sánchez-Cabo Fátima
Published: April 2021

Circadian-regulated genes are essential for tissue homeostasis and organismal function, and are therefore common targets of scrutiny. Detection of rhythmic genes using current analytical tools requires exhaustive sampling, a demand that is costly and raises ethical concerns, making it unfeasible in certain mammalian systems. Several non-parametric methods have been commonly used to analyze short-term (24 h) circadian data, such as JTK_cycle and MetaCycle. However, algorithm performance varies greatly depending on various biological and technical factors. Here, we present CircaN, an ad-hoc implementation of a non-linear mixed model for the identification of circadian genes in all types of omics data. Based on the variable but complementary results obtained through several biological and in silico datasets, we propose a combined approach of CircaN and non-parametric models to dramatically improve the number of circadian genes detected, without affecting accuracy. We also introduce an R package to make this approach available to the community.
Printing strategies for scaling-up perovskite solar cells
Authors: Wang Yulong , Duan Changyu , Lv Pin , Ku Zhiliang , Lu Jianfeng , Huang Fuzhi , Cheng Yi-Bing
Published: April 2021

Photovoltaic technology offers a sustainable solution to the problem of soaring global energy demands. Recently, metal halide perovskite solar cells (PSCs) have attracted worldwide interest because of their high power conversion efficiency of 25.5% and great potential in becoming a disruptive technology in the photovoltaic industry. The transition from research to commercialization requires advancements of scalable deposition methods for both perovskite and charge transporting thin films. Herein, we share our view regarding the current challenges to fabrication of PSCs by printing techniques. We focus particularly on ink technologies, and summarize the strategies for printing uniform, pinhole-free perovskite films with good crystallinity. Moreover, the stability of perovskite solar modules is discussed and analyzed. We believe this review will be advantageous in the area of printable electronic devices.
Integrated Surveillance for Antimicrobial Resistance in Salmonella From Clinical and Retail Meat Sources Reveals Genetically Related Isolates Harboring Quinolone- and Ceftriaxone-Resistant Determinants
Authors: M’ikanatha Nkuchia M , Yin Xin , Boktor Sameh W , Dettinger Lisa A , Tewari Deepanker
Published: April 2021

Background

Antimicrobial resistance in foodborne pathogens, including nontyphoidal Salmonella (NTS), is a public health concern. Pennsylvania conducts integrated surveillance for antimicrobial resistance in NTS from human and animal sources.

Methods

During 2015–2017, clinical laboratories submitted 4478 NTS isolates from humans and 96 isolates were found in 2520 retail meat samples. One hundred nine clinical isolates that shared pulsed-field gel electrophoresis patterns with meat isolates and all strains from meat samples were tested for susceptibility to antimicrobial agents. Six clinical and 96 NTS isolates from meat sources (total 102) were analyzed by whole-genome sequencing (WGS).

Results

Twenty-eight (25.7%) of the 109 clinical NTS and 21 (21.9%) of strains from meat sources had resistance to ≥3 antimicrobial drug classes (multidrug resistance). Sixteen of the 102 (15.7%) isolates analyzed by WGS had resistance mechanisms that confer resistance to expanded-spectrum cephalosporins, such as ceftriaxone. We identified blaCTX-M-65 in 2 S. Infantis isolates from clinical and 3 S. Infantis isolates from meat sources. These 5 blaCTX-M-65–positive S. Infantis strains carried ≥5 additional resistance genes plus a D87Y mutation in gyrA that encodes fluoroquinolone resistance. WGS showed that isolates from patients and meat samples were within ≤10 and ≤5 alleles for S. Infantis and S. Reading, respectively.

Conclusions

A significant proportion of NTS isolates from human and animal sources were multidrug resistant and 16% had genetic mechanisms that confer resistant to ceftriaxone. These results emphasize need for integrated surveillance in healthcare and agricultural settings.
P033 Scleroderma-like fibrotic disorder associated with a gastro-intestinal stromal tumour which responded only to imatinib
Authors: Butt Zaran A , NG Wan Lin , Howard Donough , Osman Kamal
Published: April 2021

Background/Aims 

Gastro-intestinal stromal tumour (GIST) is recognised as the most prevalent mesenchymal tumour of the gastro-intestinal (GI) tract. The vast majority of GIST display activating mutations in receptor tyrosine kinases, such as platelet-derived growth factor receptor alpha (PDGFRA) and c-kit. This characteristic has lead to the development and approval of targeted therapies such as Imatinib for metastatic GIST. Scleroderma is an idiopathic fibrotic syndrome which involves excess collagen deposition in multiple tissues and organs. There is emerging evidence that dysfunctional fibroblasts are central to the underlying pathogenesis of this disease. An increasing awareness of the complex interplay of these fibroblasts with other cells and inflammatory mediators, such as platelet-derived growth factor (PDGF), is being recognised. This novel case serves to further develop our understanding of these pathological interactions, and to highlight a prospective role for Imatinib in disrupting them.

Methods 

We present a case report below.

Results 

A 54-year-old Caucasian male was referred to our rheumatology clinic due to worsening Raynaud's syndrome, arthralgia, and dry cough. He subsequently developed weight loss, pyrosis and skin thickening. This clinical picture was suggestive of a new diagnosis of systemic sclerosis. However, fibrotic skin changes did not extend to the distal finger, and anti-nuclear antibody (ANA) was negative. Symptoms were also refractory to various vasodilator and immunosuppressive therapies, including nifedipine, repeated iloprost infusions, azathioprine, mycophenolic acid, prednisolone, and sildenafil. Computed tomography (CT) imaging revealed interstitial pulmonary fibrosis and a mass within the gastric fundus. Histopathologic features and immunological staining of this mass were consistent with a GIST. Resection of the tumour did not improve fibrotic symptoms. Surveillance imaging one-year later was highly concerning for metastatic recurrence, which was later confirmed with tissue biopsy. He was subsequently initiated on Imatinib therapy, which led to a rapid improvement in fibrotic changes within weeks.

Conclusion 

While there have been previous descriptions of para-neoplastic fibrotic syndromes, this is the first reported case of a scleroderma-mimicking disorder associated with GIST. It hints at an important potential overlap in the pathogenesis of these disease processes, and a potential role for tyrosine-kinase inhibitors in the treatment of scleroderma-like fibrotic disorders.

Disclosure 

Z.A. Butt: None. W. Ng: None. D. Howard: None. K. Osman: None.
P037 DMARDs & hepatitis E: the hidden culprit
Authors: Brown Geraint A , Kearney Louise , Warner Elizabeth , Ellis Spencer
Published: April 2021

Background/Aims 

Disease-modifying anti-rheumatic drugs (DMARDs) require blood monitoring as recommended by the British Society for Rheumatology guidelines. Deranged liver function tests are a common abnormality, and when a significant transaminitis occurs further investigations are required. We wish to present three cases where a transaminitis was caused by acute hepatitis E. Hepatitis E rarely causes illness in the general population. Transmission can occur via sewage-contaminated food and water, undercooked or raw pig and game meat, or processed pork and shellfish. Blood transfusion and solid organ transplantation is very rare. There is an estimated 60,000 cases of Hepatitis E per year in England. Those who are immunosuppressed are more likely to develop chronic liver disease.

Methods 

.

Results 

Case 1 is 55 year old male with a seronegative inflammatory arthritis treated with methotrexate and sulfasalazine whose ALT rose to 2043 U/l. After a negative liver screen including autoantibodies, Hepatitis E IgM was detected. Case 2 is a 71 year old male with seropositive rheumatoid arthritis prescribed Methotrexate and Sulfasalazine who developed a transaminitis following a holiday to Spain. Hepatitis E serology was positive. Case 3 is a 65 year old male with seropositive rheumatoid arthritis on Abatacept and Methotrexate who also developed deranged liver function tests following a trip to Spain. Alcohol excess was initially suspected due to the consumption of > 20 units per week. However, on cessation of all medications the ALT continued to rise to 1087 U/l. He was found to be Hepatitis E IgM positive with viral PCR also detected. In all three cases contaminated food was likely to be the source of infection and DMARDs were successfully restarted in all patients following normalisation of liver function tests.

Conclusion 

This case series highlights an important differential for transaminitis with very little published literature. Hepatitis E is under reported and not routinely requested in practice as part of a liver screen. Failure to check Hepatitis E serology may lead to DMARDs being discontinued inappropriately. All patients should be educated about the risks of Hepatitis E from food products.We recommend that DMARDs are suspended once Hepatitis E infection has been diagnosed in order to allow the immune system combat the infection. Treatment is usually self limiting, though in severe cases Ribavirin has been used with good effect. DMARDs should be restarted once liver markers normalise, and two serum Hepatitis E RNA results and two stool samples are negative. The presence of persistent Hepatitis E RNA (viral shedding) is highly suspicious for chronic infection, which would warrant hepatology input.

Disclosure 

G.A. Brown: None. L. Kearney: None. E. Warner: None. S. Ellis: None.
P045 Nothing is too 'cagey' for the rheumatologist
Authors: Kazmi Muhammad F
Published: April 2021

Background/Aims 

Rheumatological conditions can present with a number of non-specific features like arthralgia, fever, fatigue, weight loss along with raised inflammatory markers and positive antibodies. Due to this, when similar symptoms are referred for input it is very important to consider other ‘mimics’. We report a case of Pigeon fancier’s lung presenting with these symptoms which was referred as likely connective tissue disease.

Methods 

A 52-year-old lady of South Asian origin was referred by her GP with six month history of 3kg weight loss, arthralgia, fatigue, low grade fever and persistently raised inflammatory markers (ESR ranging from 50-64 mm/hr, CRP 10-14 mg/L, normal BMI). On further questioning there was history of mouth ulcers, non-specific rash, occasional cough but no Raynaud’s or joint swelling. Blood investigations showed weakly positive ANA and RF but negative ENA, DNA, antiCCP , CK, C3,C4. C-ANCA was positive but PR3 negative. CXR was clear and tests for chronic infections including TB were negative. Due to lack of objective CTD signs, plan was to take a careful monitoring approach to see if clinical features evolved. A month later due to worsening cough, a CT chest/abdomen arranged by GP showed ground-glass changes consistent with pneumonitis and hence her rheumatology appointment was expedited to see if there was an autoimmune unifying diagnosis. She was also referred by her GP to the chest clinic in view of CT report and mild shortness of breath.

Results 

On further review, again there were no objective CTD signs. On direct questioning there was history of travelling before worsening chest symptoms to South Asia. Also around a year before her symptoms started she was given an African grey parrot. Based on this, serology for Avian precipitin was checked which showed strongly positive IgG antibodies to avian antigens (Budgerigar droppings and feathers, Pigeon feathers IgG Abs) confirming the diagnosis of pigeon fanciers lung. She fulfilled the diagnostic criteria and was asked to avoid the trigger. Urgent respiratory input was arranged where diagnosis was agreed with and disease was deemed sub-acute in presentation. Due to PFTs showing low transfer factor of 38%, Prednisolone was started with significant improvement within few days. Review of CT chest only showed inflammatory changes and no established fibrosis predicting excellent prognosis as delay in treatment can cause irreversible pulmonary fibrosis.

Conclusion 

A number of conditions can mimic rheumatological conditions which usually turn out to be either infectious or malignant in origin. This case highlights the importance of considering other differentials and along with taking a travel history also asking for other possible triggers like pets. In similar scenarios the diagnosis may be ‘cagey’ but as rheumatologists we are expected to answers questions which others can’t.

Disclosure 

M.F. Kazmi: None.
P048 Cytomegalovirus retinitis in a patient with rheumatoid arthritis on tofacitinib
Authors: Beharry Karen , Kaur Simerdip , Papagiannuli Efrosini , Moses Samuel , Lord Denise De
Published: April 2021

Background/Aims 

Cytomegalovirus (CMV) retinitis is one of the most common opportunistic ocular infections and has traditionally been associated with immunocompromised individuals. We present a case of CMV retinitis following 3 months of treatment with tofacitinib in conjunction with methotrexate (MTX) for rheumatoid arthritis (RA) in an elderly lady with no other co-morbidities.

Methods 

The case is presented below.

Results 

69-year-old lady with long standing seronegative, anti-cyclic citrullinated peptide negative, erosive RA since 2016. She was intolerant of sulphasalazine, leflunamide, methotrexate and etanercept. Hydroxychloroquine was avoided due to idiopathic cystoid macular oedema in the right eye with a baseline visual acuity of 6/18. Baseline fundus fluorescein angiogram (FFA) was negative for any vascular, inflammatory or occlusive disease. She was escalated to tofacitinib in August 2019. Approximately 3 months later, she noticed significantly reduced vision in her right eye from 6/18 down to 6/60. She had an FFA and Indocyanine Green Angiography, which showed quite extensive retinal ischaemia and vasculitis. Her bloods revealed a raised serum ACE and a T-spot test from 2018 was reactive followed by a repeat in 2019 which was equivocal. Tofacitinib was discontinued. She was commenced on rifampicin and isoniazid as 3 months prophylaxis for latent tuberculosis (LTBI). Additionally, she was started on oral prednisolone 60mg daily for presumed sarcoid related retinal vasculitis. She failed to improve despite a week’s treatment and subsequently had a vitreous aspirate which was strongly positive for CMV PCR. Her CMV viral load was 267copies/ml. The aspirate was negative for other infectious agents. She was commenced on valganciclovir for CMV retinitis. Unfortunately, her vision remained unchanged despite the viral load becoming undetectable a few weeks later. Despite having LTBI, there was no reactivation of this with her immunosuppressive therapy.

Conclusion 

CMV retinitis is usually associated with immunocompromised individuals and is rarely encountered related to tofacitinib therapy for rheumatoid arthritis. Tofacitinib suppresses T cell function by inhibiting STAT signalling pathways, modulating T cell activation and cytokine production. Our case highlights the preferential development of CMV retinitis over active TB in the presence of LTBI, which is a recognised risk with the use of JAK kinase inhibitors. TB risk has been associated with genetic mutations in IL-12, IFN-γ and STAT1 pathways while CMV activation may be influenced by mutations in HLA ,Toll-like receptors, immunoglobulin light chain antibodies, IFN lambda region as well as alternative transcripts of the CMV viral major immediate early genes.

Disclosure 

K. Beharry: None. S. Kaur: None. E. Papagiannuli: None. S. Moses: None. D. De Lord: None.
P064 The impact of the COVID-19 pandemic on outpatient services: an analysis of patient feedback of virtual outpatient clinics in a tertiary teaching centre with a focus on musculoskeletal and rheumatology services
Authors: Byravan Swetha , Sunmboye Kehinde
Published: April 2021

Background/Aims 

Due to the COVID-19 pandemic there have been changes to NHS services to limit unnecessary patient hospital visits and comply with new social restriction rules. One of these changes has been the introduction of virtual consultations in outpatient clinics to replace traditional face to face appointments.

Methods 

A retrospective analysis of patient feedback from adult outpatient virtual appointments in a 4-month period was collated and reviewed (May-September 2020). After an appointment, patients were sent a text message asking for feedback. The text consisted of one main question asking patients to rate their experience and a comment section. The data from this brief patient survey was obtained for all rheumatology patient responses. At the end of the text there was a link for a more comprehensive online survey which patients could fill out if they wish to provide more detailed feedback. Responses to this survey encompasses all adult outpatient specialities including musculoskeletal services.

Results 

There were 269 responses to the detailed patient survey from various adult outpatient clinics. The most common type of virtual consultation was telephone which was the case in 79%, of which 91% of patients stated the caller was polite and 89% felt they had an opportunity to ask questions. When asked what their overall view 43% of patients stated they would not mind conducting all future appointments via telephone, 23.5% felt that in the current situation a telephone consultation was acceptable but would have preferred a face to face and 7% were completely unsatisfied. From the musculoskeletal group there were 36 responses (20 orthopaedic, 15 rheumatology and 1 musculoskeletal). 92% of patients stated they were given the opportunity to ask questions and 86% were satisfied with the advice given to them. 33% (n = 12) stated they would not mind having virtual consultations in the future even after the pandemic, but 28% stated they would have preferred a face to face consultation. There were 784 responses to the shorter patient survey via text message from rheumatology patients. When asked to rate their experience 94% (n = 739) of patients stated it was either good or very good, and only 1% said it was poor or very poor. There were largely positive comments in the feedback. Most frequent points were patients felt listened to, communication was good and virtual consultations were less stressful.

Conclusion 

At present the use of virtual clinics seems to be well received by patients and most importantly their quality of care is not compromised. From a patient’s perspective there are many benefits and cumulative feedback so far suggests that majority of the patients are willing to adapt to this new approach to outpatient appointments both now and post-COVID-19.

Disclosure 

S. Byravan: None. K. Sunmboye: None.
P093 Sleep characteristics and frailty in men: the influence of testosterone
Authors: Sharma Seema D , Cook Michael J , Vanderschueren Dirk , Antoniou Leen , Gielen Evelien , Wu Frederick C , O’Neill Terence W
Published: April 2021

Background/Aims 

Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, though it has been suggested that hormonal factors may play a role. The aim of this analysis was to determine the association between sleep duration, sleep quality and frailty in middle age and older European men and the influence of testosterone on these associations.

Methods 

Men aged 40-79 years were recruited from population samples in eight European centres for participation in the European Male Age Study. Participants were interviewed and asked also to complete a questionnaire about sleep which included a question about average number of hours sleep per night and questions about sleep quality. Sleep quality was scored 0-20 with higher score indicating poor quality. A frailty index (FI) was constructed. Participants also had a single fasting morning venous blood sample taken and total testosterone measured using gas chromatography mass spectrometry. Using negative binomial regression we looked at the association between sleep duration, sleep quality and frailty (outcome; range 0-100) with the results adjusted for putative confounders and also testosterone level.

Results 

2,369 participants contributed data to the analysis. Mean sleep duration was 7.01 hours. 256 (10.7%) participants had sleep quality scores between 10 -14 and 101 (4.2%) participants’ scores were between 15 and 20. Mean (standard deviation) testosterone level was 16.4 (6.2) pmol/l and 14.7% of subjects had a low testosterone level (<10.5pmol/l). After adjustment for age, centre, body mass index, depression, pain, alcohol intake and smoking, compared to those with a sleep score of 0-4, those with scores of 10-14 and 15-20 were more likely to have a higher frailty index (RR = 1.37; 95% CI 1.25,1.49) and (RR = 1.57; 95% CI 1.38, 1.78) respectively. Further adjustment for testosterone did not influence the strength of these associations. Compared to those with sleep 6-8 hours, those with less than 5 hours had a significantly higher FI (RR = 1.16; 95% CI 1.06, 1.28) and also those with a longer sleep duration (9 hours or more) had a significantly increased FI (RR = 1.11; 95% CI 1.00, 1.23). Further adjustment for testosterone did not influence the strength of these associations.

Conclusion 

Frailty is associated with impaired sleep quality and also sleep duration. The mechanism is unknown though cannot be explained by testosterone level.

Disclosure 

S.D. Sharma: None. M.J. Cook: None. D. Vanderschueren: None. L. Antoniou: None. E. Gielen: None. F.C. Wu: None. T.W. O’Neill: None.
P115 Improved reporting of vertebral fractures by radiologists: a success story!
Authors: Nazir Muhammad Amjad , Jamal Muhammad Safwan , Hart Darren , Shipley Jacqueline , Warren Susie , Hardcastle Sarah , Ahmed Tehseen
Published: April 2021

Background/Aims 

Vertebral fractures (VF) are the most common type of osteoporotic fracture and affect >20% women over the age of 80. However, the majority remain undiagnosed. Even when imaging has been performed, VF are under-reported by radiologists. This results in a missed opportunity for treatment to reduce fracture risk and morbidity. We conducted this project to improve the reporting of VF (incidental or symptomatic), thus enabling our fracture liaison service to identify cases more easily and optimise patient care.

Methods 

Using SYNAPSE (imaging software), cohorts of patients aged more than 75 years of age who had CT scans of chest/abdomen/pelvis in 2012 and 2017 were selected. Images were reviewed by a single rheumatologist with an interest in osteoporosis, looking for the presence of VF. For patients with VF, radiology reports were reviewed to assess whether there was documentation of this.

Results 

There was improvement in the reporting of VF between 2012 and 2017 (see Table 1) but identification remained suboptimal. Specific use of the term “fracture” remained in the minority. The data was presented to our radiologists in December 2017 along with information about the importance of identifying and treating patients with VF. Agreement was reached for the radiologists to include a code (FLS) in reports where a non-pathological VF was identified. Searches for the presence of the code through the hospital’s radiology information system have allowed easy identification of VF cases. Letters are sent to Primary Care teams informing them that we have identified an incidental VF along with suggested management advice. This project has substantially increased the number of VF identified (in patients aged >50) by our fracture liaison service over time. 82 cases of VF were identified in 2017 (pre-intervention), 350 cases in 2018, and 848 cases in 2019. P115 Table 1:No. of patients, nVF identified in audit, n (%)Terminology alluding to fracture in radiology report, n (% of identified fractures)Use of the word “fracture” in radiology report, n (% of identified fractures)Mention of osteoporosis or osteopaenia, n (% of identified fractures)2012 cohort10315 (15)5 (33)1 (7)3 (20)2017 cohort10226 (25)18 (69)8 (31)4 (15)

Conclusion 

Collaboration with our radiologists through education and the use of a code in radiology reports has resulted in a sustained and dramatic increase in the number of VF annually identified by our fracture liaison service. We strongly recommend that other services adopt this approach to help them achieve national audit targets and improve patient care.

Disclosure 

M. Nazir: None. M. Jamal: None. D. Hart: None. J. Shipley: None. S. Warren: None. S. Hardcastle: None. T. Ahmed: None.
P147 Safety of AbatacePt in Rheumatoid arthritis associated Interstitial Lung disease (APRIL)
Authors: Gudu Tania , Stober Carmel , Fifield Maeve , Babar Judith , Ostor Andrew , Parfrey Helen , Hall Francess
Published: April 2021

Background/Aims 

Interstitial lung disease (ILD) is the commonest extra-articular complication of rheumatoid arthritis (RA) and is associated with a median survival of 3-8 years. Although biologic therapies are effective for synovitis, they can exacerbate the ILD. RA patients with significant ILD but minimal synovitis have limited therapeutic options. Case reports and retrospective analyses suggest that Abatacept may have efficacy in RA-ILD. However, use of potent immunosuppression in patients with chronic lung disease may increase the incidence of lower respiratory tract infection (LRTI). The purpose of this prospective study was to evaluate the safety of Abatacept in patients with progressive RA-ILD.

Methods 

This was a prospective, open-label, study of 19 RA patients (2010 ACR/EULAR criteria) with ILD. Patients were included if either serial thoracic computed tomography (CT) or pulmonary function tests (PFT) indicated progressive ILD over the preceding 14 months. Intravenous Abatacept was administered at baseline, 2, 4, 8, 12, 16 and 20 weeks. PFTs, thoracic CT scan and questionnaires were performed at baseline and week 20. The number of LRTI was recorded. Primary outcome: change in Forced Vital Capacity (FVC). Secondary outcomes: Transfer Factor (TLCOc), King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire, the Leicester Cough Questionnaire (LCQ) and radiological scores (percentage involvement of lung fields scored separately for ground-glass opacification, fibrosis, honeycombing and consolidation).

Results 

Preliminary data from the study are reported. Ten patients completed the study: 6 male, 6 ex-smokers, mean age 68±8.21 years, mean RA duration 6±5.4 years. The APRIL study was terminated due to safety concerns in the context of COVID-19 pandemic; nine patients were withdrawn for this reason. LRTI occurred in 4 patients (one patient had 2 LRTI). There were no serious adverse reactions. The mean FVC remained stable during the course of the study. There was a trend towards improvement in the LCQ and improvement in the K-BILD score. ILD-related changes on thoracic CT were stable in 9 of the patients.

Conclusion 

Our data indicates that abatacept has an acceptable safety profile in progressive pulmonary fibrosis associated with RA-ILD. This small dataset also suggests that ILD has not progressed during the period of treatment. P147 Table 1:Summary of outcomes after 20 weeks’ treatment with Abatacept in RA patients with progressive interstitial lung diseaseN = 10Baseline20 WeekFVC (L)2.78 ± 0.903.0 ± 0.89TLCOc (mmol/min/kPa)3.75 ± 1.033.72 ± 1.00K-BILD49.10 ± 5.5054.40 ± 6.0LCQ4.78 ± 1.514.82 ± 1.32

Disclosure 

T. Gudu: None. C. Stober: None. M. Fifield: None. J. Babar: None. A. Ostor: None. H. Parfrey: None. F. Hall: Grants/research support; FH has received a grant of £168k from Bristol Myers Squibb for the APRIL study.
P149 The intracellular chloride channel 4 (CLIC4) plays an important role in systemic sclerosis fibroblast activation
Authors: Wasson Christopher , Ross Rebecca , Morton Ruth , Mankouri Jamel , Del Galdo Francesco
Published: April 2021

Background/Aims 

The intracellular chloride ion channel CLIC4 mediates the activation of cancer associated fibroblasts. Interestingly, systemic sclerosis (SSc) fibroblasts display a number of similar properties to cancer associated fibroblasts. Tissue fibrosis in SSc is driven by active fibroblasts (myofibroblasts). Therefore in this study we investigated the role of CLIC4 in SSc fibroblast activation.

Methods 

Dermal fibroblasts were obtained from full thickness skin biopsies from SSc patients (early-diffuse). RNA and protein were collected from the fibroblasts and CLIC4 transcript and protein levels were assessed by qPCR and western blot. SSc patient fibroblasts were treated with the chloride ion channel inhibitors NPPB and IAA-94.

Results 

CLIC4 was found to be expressed at significantly higher levels in SSc patients fibroblasts compared to healthy controls, at both the transcript (3.7 fold) and protein (1.7 fold) levels. Inhibition of the TGF-β signalling pathway led to reduced CLIC4 expression in SSc fibroblasts, confirming this pathway as the main driver of CLIC4 expression. Finally, treatment of SSc fibroblasts with small molecule inhibitors that target the channel led to reduced expression of the myofibroblast markers collagen type 1 and alpha-smooth muscle actin, suggesting a direct role for CLIC4 in SSc associated skin fibrosis.

Conclusion 

We have identified a novel role for CLIC4 in SSc myofibroblast activation, which further strengthen the similarities between SSc fibroblasts and cancer associated fibroblasts. Furthermore this study highlights this channel as a novel target for therapeutic intervention.

Disclosure 

C. Wasson: None. R. Ross: None. R. Morton: None. J. Mankouri: None. F. Del Galdo: None.
P166 Multimorbidity in SLE, a barrier to clinical trial eligibility: results from the BILAG-BR
Authors: Dyball Sarah , Collinson Sophie , Sutton Emily , McCarthy Eoghan , Parker Ben ,   British Isles Lupus Assessment Group Biologics Register (BILAG-BR) consortium, Bruce Ian
Published: April 2021

Background/Aims 

Stringent inclusion and exclusion criteria are employed in SLE clinical trials. Organ dysfunction and co-morbidities are common exclusion criteria which may affect how representative trials are of real-world SLE populations. We aimed to apply published trial eligibility criteria to patients with SLE in a large national register.

Methods 

A literature review of all major published double-blinded randomised phase III trials in non-renal SLE was performed. Common inclusion and exclusion criteria were applied to all patients recruited to the BILAG-Biologics Register (BILAG-BR), a large UK-wide register of SLE patients. Data on comorbidities for all patients registered was collected. The mean (SD) number of co-morbidities was calculated. Patients were then classified as being eligible or ineligible. Groups were compared initially using a chi-squared or Wilcoxon rank-sum test and logistic regression model was used to test the age and sex adjusted association between trial eligibility and comorbidities.

Results 

Common inclusion and exclusion criteria were identified from 12 published trials. When applied to the 837 patients recruited to BILAG-BR, 562 (67%) patients would not be eligible for inclusion in these trials. Ineligible patients had a shorter disease duration (2.9 vs. 5.1 years, p < 0.01), but were similar in age (P = 1.0), sex (P = 0.7) and ethnicity (p = 0.5) to those who were eligible. Of eligible patients, 128 (53%) had 1 or more comorbidities compared with 340 (60%) who were ineligible (p = 0.05). The mean (SD) number of comorbidities was 0.9 (1.2) vs 1.2 (1.3) for eligible and ineligible patients respectively. After adjusting for age and sex, inclusion in clinical trials was associated with fewer comorbidities (OR 0.81, 95% CI 0.70, 0.94, p < 0.01).

Conclusion 

Patients with multi-morbidity are more likely to be ineligible for SLE clinical trials. Evidence from real world studies and registers are therefore needed to fully understand the safety and effectiveness of new therapies. Our data also underscores the need to develop more pragmatic eligibility criteria for clinical trials.

Disclosure 

S. Dyball: None. S. Collinson: None. E. Sutton: None. E. McCarthy: None. B. Parker: Consultancies; GSK, AstraZenica, UCB, Abbvie, Pfizer, BMS, Celltrion. Grants/research support; GSK, Sanofi Genzyme. I. Bruce: Consultancies; GSK, Medimmune, AstraZenica, Eli Lilly, Merck Serono, UCB, ILTOO. Member of speakers’ bureau; AstraZeneca, Medimmune, GSK, UCB. Grants/research support; GSK, Genzyme Sanofi, UCB.
P197 Evaluating the patient experience of the Barts Health MySpA app for axial spondyloarthritis and psoriatic arthritis
Authors: Adshead Rebecca , Donnelly Simon , Shaikh Maliha
Published: April 2021

Background/Aims 

In 2018, MySpA App was developed and launched by the Rheumatology team at Whipps Cross Hospital to empower patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) in self-management of their condition. MySpA is an internationally available, free educational App providing instant access to evidence based medical information about axSpA and PsA. It includes a library of exercise videos created by specialist physiotherapists in axSpA, enabling patients and clinicians to build exercise programmes tailored to individual patient needs. Validated outcome measures can be completed by patients throughout the year, with the option of sharing those results with their rheumatology clinicians. Our objective was to evaluate patient opinion and usefulness of MySpA among our patients.

Methods 

Two years since MySpA was launched at BSR, an online questionnaire was sent to 198 patients with axSpA and PsA from Whipps Cross Rheumatology Service. The questions enquired about awareness of MySpA for download and use amongst patients with managing their condition.

Results 

Overall response was 36% (n = 72). 61% (n = 44) of the patients responded had downloaded MySpA with 64%(n = 28) of those patients using the app throughout the year. The majority that had not downloaded, were not aware the app existed (70%). All features within the app were used, with the axSpA and PsA Information section and exercise library most popular with comments “I use my exercise plan daily” and “great app.” 53% of patients used the app as an educational resource and 46% used the exercise library tailored to their own needs. The most common reason for not using the app was forgetting (29%). The majority (91%) would recommend MySpA to other patients with axSpA and PsA, with 63% reported MySpA supported them managing their condition.

Conclusion 

MySpA is well received by patients with axSpA and PsA at Whipps Cross Hospital as a resource where they find specialist support, information and exercise guidance to empower management. It provides a useful virtual tool to assist patients take control of their arthritis and track and monitor their condition and has been particularly useful in this regard during the Covid pandemic. Patients used the facility to complete and share their assessment results and journal logs virtually with their healthcare team. However, continual awareness of MySpA amongst patients and clinicians is required to enable the opportunity to utilise instant specialist support and direction that may help patients manage their condition. The usefulness of the virtual monitoring feature of the app amongst clinicians should be explored in future research.

Disclosure 

R. Adshead: None. S. Donnelly: None. M. Shaikh: None.