bluuebunny/crossref_metadata_2025 huggingface dataset:
Beauveria bassiana rewires molecular mechanisms related to growth and defense in tomato
Authors: Proietti Silvia , Falconieri Gaia Salvatore , Bertini Laura , Pascale Alberto , Bizzarri Elisabetta , Morales-Sanfrutos Julia , Sabidó Eduard , Ruocco Michelina , Monti Maurilia M , Russo Assunta , Dziurka Kinga , Ceci Marcello , Loreto Francesco , Caruso Carla
Published: April 2023

Plant roots can exploit beneficial associations with soil-inhabiting microbes, promoting growth and expanding the immune capacity of the host plant. In this work, we aimed to provide new information on changes occurring in tomato interacting with the beneficial fungus Beauveria bassiana. The tomato leaf proteome revealed perturbed molecular pathways during the establishment of the plant–fungus relationship. In the early stages of colonization (5–7 d), proteins related to defense responses to the fungus were down-regulated and proteins related to calcium transport were up-regulated. At later time points (12–19 d after colonization), up-regulation of molecular pathways linked to protein/amino acid turnover and to biosynthesis of energy compounds suggests beneficial interaction enhancing plant growth and development. At the later stage, the profile of leaf hormones and related compounds was also investigated, highlighting up-regulation of those related to plant growth and defense. Finally, B. bassiana colonization was found to improve plant resistance to Botrytis cinerea, impacting plant oxidative damage. Overall, our findings further expand current knowledge on the possible mechanisms underlying the beneficial role of B. bassiana in tomato plants.
A new perspective on completeness and finitist consistency
Authors: Santos Paulo Guilherme , Sieg Wilfried , Kahle Reinhard
Published: April 2023

In this paper, we study the metamathematics of consistent arithmetical theories $T$ (containing $\textsf {I}\varSigma _{1}$); we investigate numerical properties based on proof predicates that depend on numerations of the axioms. Numeral Completeness. For every true (in $\mathbb {N}$) sentence $\vec {Q}\vec {x}.\varphi (\vec {x})$, with $\varphi (\vec {x})$ a $\varSigma _{1}(\textsf {I}\varSigma _1)$-formula, there is a numeration $\tau $ of the axioms of $T$ such that $\textsf {I}\varSigma _1\vdash \vec {Q}\vec {x}. \texttt {Pr}_{\tau }(\ulcorner \varphi (\overset {\text{.} }{\vec {x}})\urcorner )$, where $\texttt {Pr}_{\tau }$ is the provability predicate for the numeration $\tau $.

Numeral Consistency. If $T$ is consistent, there is a $\varSigma _{1}(\textsf {I}\varSigma _1)$-numeration $\tau $ of the axioms of $\textsf {I}\varSigma _{1}$ such that $\textsf {I}\varSigma _1\vdash \forall\, x. \texttt {Pr}_{\tau }(\ulcorner \neg \textit {Prf}(\ulcorner \perp \urcorner , \overset {\text{.}}{x})\urcorner )$, where $\textit {Prf}(x,y)$ denotes a $\varDelta _{1}(\textsf {I}\varSigma _1)$-definition of ‘$y$ is a $T$-proof of $x$’. Finitist consistency is addressed by generalizing a result of Artemov:

Partial finitism. If $T$ is consistent, there is a primitive recursive function $f$ such that, for all $n\in \mathbb {N}$, $f(n)$ is the code of an $\textsf {I}\varSigma _{1}$-proof of $\neg\, \textit{Prf}(\ulcorner \perp \urcorner ,\overline {n})$.

These results are not in conflict with Gödel’s Incompleteness Theorems. Rather, they allow to extend their usual interpretation and show a deep connection to reflections in Hilbert’s last papers of 1931.
Stable bulged G-quadruplexes in the human genome: identification, experimental validation and functionalization
Authors: Papp Csaba , Mukundan Vineeth T , Jenjaroenpun Piroon , Winnerdy Fernaldo Richtia , Ow Ghim Siong , Phan Anh Tuân , Kuznetsov Vladimir A
Published: April 2023

DNA sequence composition determines the topology and stability of G-quadruplexes (G4s). Bulged G-quadruplex structures (G4-Bs) are a subset of G4s characterized by 3D conformations with bulges. Current search algorithms fail to capture stable G4-B, making their genome-wide study infeasible. Here, we introduced a large family of computationally defined and experimentally verified potential G4-B forming sequences (pG4-BS). We found 478 263 pG4-BS regions that do not overlap ‘canonical’ G4-forming sequences in the human genome and are preferentially localized in transcription regulatory regions including R-loops and open chromatin. Over 90% of protein-coding genes contain pG4-BS in their promoter or gene body. We observed generally higher pG4-BS content in R-loops and their flanks, longer genes that are associated with brain tissue, immune and developmental processes. Also, the presence of pG4-BS on both template and non-template strands in promoters is associated with oncogenesis, cardiovascular disease and stemness. Our G4-BS models predicted G4-forming ability in vitro with 91.5% accuracy. Analysis of G4-seq and CUT&Tag data strongly supports the existence of G4-BS conformations genome-wide. We reconstructed a novel G4-B 3D structure located in the E2F8 promoter. This study defines a large family of G4-like sequences, offering new insights into the essential biological functions and potential future therapeutic uses of G4-B.
DIANA-microT 2023: including predicted targets of virally encoded miRNAs
Authors: Tastsoglou Spyros , Alexiou Athanasios , Karagkouni Dimitra , Skoufos Giorgos , Zacharopoulou Elissavet , Hatzigeorgiou Artemis G
Published: April 2023

DIANA-microT-CDS is a state-of-the-art miRNA target prediction algorithm catering the scientific community since 2009. It is one of the first algorithms to predict miRNA binding sites in both the 3′ Untranslated Region (3′-UTR) and the coding sequence (CDS) of transcripts, with increased performance. Its current version, DIANA-microT 2023 (www.microrna.gr/microt_webserver/), brings forward a significantly updated set of interactions. DIANA-microT-CDS has been executed utilizing annotation information from Ensembl v102, miRBase 22.1 and, for the first time, MirGeneDB 2.1, yielding more than 83 million interactions in human, mouse, rat, chicken, fly and worm species. Additionally, this version delivers predicted interactions of miRNAs encoded from 20 viruses against host transcripts from human, mouse and chicken species. Numerous resources have been interconnected into DIANA-microT, including DIANA-TarBase, plasmiR, HMDD, UCSC, dbSNP, ClinVar, as well as miRNA/gene abundance values for 369 distinct cell-lines/tissues. The server interface has been redesigned allowing users to use smart filtering options, identify abundance patterns of interest, pinpoint known SNPs residing on binding sites and obtain miRNA-disease information. The contents of DIANA-microT webserver are freely accessible and can also be locally downloaded without any login requirements.
SUP: a probabilistic framework to propagate genome sequence uncertainty, with applications
Authors: Becker Devan , Champredon David , Chato Connor , Gugan Gopi , Poon Art
Published: April 2023

Genetic sequencing is subject to many different types of errors, but most analyses treat the resultant sequences as if they are known without error. Next generation sequencing methods rely on significantly larger numbers of reads than previous sequencing methods in exchange for a loss of accuracy in each individual read. Still, the coverage of such machines is imperfect and leaves uncertainty in many of the base calls. In this work, we demonstrate that the uncertainty in sequencing techniques will affect downstream analysis and propose a straightforward method to propagate the uncertainty. Our method (which we have dubbed Sequence Uncertainty Propagation, or SUP) uses a probabilistic matrix representation of individual sequences which incorporates base quality scores as a measure of uncertainty that naturally lead to resampling and replication as a framework for uncertainty propagation. With the matrix representation, resampling possible base calls according to quality scores provides a bootstrap- or prior distribution-like first step towards genetic analysis. Analyses based on these re-sampled sequences will include a more complete evaluation of the error involved in such analyses. We demonstrate our resampling method on SARS-CoV-2 data. The resampling procedures add a linear computational cost to the analyses, but the large impact on the variance in downstream estimates makes it clear that ignoring this uncertainty may lead to overly confident conclusions. We show that SARS-CoV-2 lineage designations via Pangolin are much less certain than the bootstrap support reported by Pangolin would imply and the clock rate estimates for SARS-CoV-2 are much more variable than reported.
Quasi-prime peptides: identification of the shortest peptide sequences unique to a species
Authors: Mouratidis Ioannis , Chan Candace S Y , Chantzi Nikol , Tsiatsianis Georgios Christos , Hemberg Martin , Ahituv Nadav , Georgakopoulos-Soares Ilias
Published: April 2023

Determining the organisms present in a biosample has many important applications in agriculture, wildlife conservation, and healthcare. Here, we develop a universal fingerprint based on the identification of short peptides that are unique to a specific organism. We define quasi-prime peptides as sequences that are found in only one species, and we analyzed proteomes from 21 875 species, from viruses to humans, and annotated the smallest peptide kmer sequences that are unique to a species and absent from all other proteomes. We also perform simulations across all reference proteomes and observe a lower than expected number of peptide kmers across species and taxonomies, indicating an enrichment for nullpeptides, sequences absent from a proteome. For humans, we find that quasi-primes are found in genes enriched for specific gene ontology terms, including proteasome and ATP and GTP catalysis. We also provide a set of quasi-prime peptides for a number of human pathogens and model organisms and further showcase its utility via two case studies for Mycobacterium tuberculosis and Vibrio cholerae, where we identify quasi-prime peptides in two transmembrane and extracellular proteins with relevance for pathogen detection. Our catalog of quasi-prime peptides provides the smallest unit of information that is specific to a single organism at the protein level, providing a versatile tool for species identification.
Interim Federal Health Program: Survey of use of supplemental benefits by paediatric health care providers
Authors: Leps Caroline , Monteiro Jessica , Barozzino Tony , Bowry Ashna , Rashid Meb , Sgro Michael , Suleman Shazeen
Published: April 2023

Objectives

The Interim Federal Health Program (IFHP) provides temporary healthcare coverage to refugees and refugee claimants. Previous research demonstrates that paediatric healthcare providers poorly utilize the IFHP, with low registration rates and limited understanding of the program. The objective of this study was to examine paediatric provider use of IFHP-covered supplemental benefits, and their experience with trying to access these benefits.

Methods

A one-time survey was administered via the Canadian Paediatric Surveillance Program in February 2020. Of those who had provided care to IFHP-eligible patients, descriptive tables and statistics were created looking at provider demographics, and experience using the IFHP supplemental benefits. A multinomial logistic regression was built to look at provider characteristics associated with trying to access supplemental benefits.

Results

Of the 2,753 physicians surveyed, there were 1,006 respondents (general paediatricians and subspecialists). Of the respondents, 526 had recently provided care to IFHP-eligible patients. Just over 30% of those who had recently provided care did not access supplemental benefits as they did not know they were covered by the IFHP. Of those who had tried to access supplemental benefits, over 80% described their experience as difficult, or very difficult.

Conclusions

Paediatric providers have a poor understanding of IFHP-covered supplemental benefits, which is cited as a reason for not trying to access supplemental benefits. Of those who do try to access these benefits, they describe the process as difficult. Efforts should be made to improve provider knowledge and streamline the process to improve access to healthcare for refugee children and youth.
The development of large public infrastructure projects: integrating policy and project studies models
Authors: Hudon Pierre-André , Floricel Serghei
Published: April 2023

Project management theory often reduces development to a simplistic and smooth process of consultation leading to a consensual set of requirements. However, in large public infrastructure projects, this is rarely the case as development is often subject to major power struggles. This article shows that public policy theory has an excellent potential to shed a fresh light on project development. An integrated model combining the theoretical insights from the Advocacy Coalition Framework and project development studies is presented and illustrated using the case of a major Canadian city streetcar network megaproject. The implications of the model for understanding “wicked problems” are discussed.
OA12 Comparing disease manifestations and outcomes in juvenile-onset SLE and adult-onset SLE patients: a nested case-control study within a Singapore cohort
Authors: Thong Bernard Y , Khong Yan-Yi , Lim Xin-Rong , Howe Hwee-Siew
Published: April 2023

Background/Aims

To compare disease manifestations and outcomes of juvenile-onset SLE (jSLE) and adult-onset SLE (aSLE) patients using a nested case-control study of patients in a Singapore cohort.

Methods

A prospective cohort of SLE patients was established at Tan Tock Seng Hospital from 1 January 2002 to 31 December 2017. Sociodemographic, clinical, laboratory and treatment data were collected according to a standardised protocol. jSLE patients (≤18 years old) were selected from this cohort and matched for gender and disease duration in a 1:1 ratio with aSLE patients. Data from the enrolment visit (V0) and last visit (VL) were analysed in this study.

Results

There were 148 jSLE patients with sufficient information for analysis who were matched with 148 aSLE patients. Fever and lymphadenopathy (p < 0.001) and hypocomplementemia (p = 0.002 at V0) were significantly more common in jSLE, while cardiovascular manifestations were significantly more common in aSLE patients (p = 0.008 at VL). Disease activity measured by the SLE Disease Activity Index (SLEDAI) was higher in the jSLE group at V0 (median SLEDAI 4 vs 2, p=0.05) and at VL (median SLEDAI 2.5 vs 0, p = 0.007). A significantly higher proportion of jSLE patients received immunosuppressants (intravenous cyclophosphamide, mycophenolate mofetil, azathioprine and ciclosporin) (p = 0.003 at V0, p < 0.001 at VL) and intravenous methylprednisolone (p < 0.001 at V0 and VL) compared to aSLE patients.

Conclusion

A higher proportion of jSLE patients have fever, lymphadenopathy, hypocomplementemia, or more active disease requiring greater use of immunosuppressants compared to aSLE patients. Early diagnosis and treatment of jSLE may prevent development of major organ involvement, in particular renal and neuropsychiatric.

Disclosure

B.Y. Thong: None. Y. Khong: None. X. Lim: None. H. Howe: None.
OA16 Identification of surrogate serum proteomic biomarkers associated with ultrasound power Doppler in psoriatic arthritis
Authors: Hum Ryan M , Nair Nisha , Ling Stephanie F , Barton Anne , Ho Pauline , Plant Darren
Published: April 2023

Background/Aims

An area of key unmet need in psoriatic arthritis (PsA) is the identification of biomarker(s) which predict those likely to respond to a specific therapy; in order to achieve that, an objective measure of disease activity would be ideal. Ultrasound power Doppler (PD) is a semi-quantitative measure of inflammation. However, ultrasound is time-consuming and requires specific expertise, whereas a blood-based surrogate biomarker of PD would be easier to apply clinically, and could serve as an objective outcome measure of response. Our aim is to identify proteomic biomarkers associated with PD in PsA patients.

Methods

Twenty-six patients with PsA (fulfilling CASPAR criteria) were recruited prospectively. All underwent 66-joint ultrasound examination and presence of PD was recorded. There were 7 patients without PD(-) and 19 with PD(+) detectable in at least 1 joint. Proteomics data for 1,073 proteins were generated using sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS). Proteins with high levels of missing data were filtered (>30%) followed by random forest analysis. Differentially expressed proteins (DEPs) based on PD status were identified. Protein-protein interaction network analysis was performed using the search tool for retrieval of interacting genes (STRING), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO).

Results

Following pre-processing, 553 proteins were available for analysis. Seventeen DEPs were identified (p-values <0.05) (Table 1). Among these, ERAP2, an enzyme involved in MHC-I ligand processing and a known risk factor for inflammatory diseases, had the largest fold change (-0.64 95%CI -1.20 to -0.07, p = 0.03). Network analysis revealed that the 17 DEPs were significantly enriched (p < 0.001) in the PD+ group. KEGG pathway analysis identified the association of the DEPs in leukocyte transendothelial migration (strength 1.5 FDR=0.04). GO analysis of the DEPs revealed involvement in immunoglobulin receptor binding (strength 2.28 FDR=0.03).

Conclusion

We identified several potential serum proteomic biomarkers correlated with disease activity, as assessed by the presence of PD, in PsA; these provide insights into the biological mechanisms underlying synovitis in PsA. Validation in a larger cohort and functional studies are required to determine the role of these proteins in mediating inflammation in PsA.

Disclosure

R.M. Hum: None. N. Nair: None. S.F. Ling: None. A. Barton: None. P. Ho: None. D. Plant: None.
OA30 Systemic sclerosis and cancer in the UK: an epidemiological analysis using the Clinical Practice Research Datalink
Authors: Pauling John D , Snowball Julia , McHugh Neil , McGrogan Anita
Published: April 2023

Background/Aims

After cardiopulmonary disease, cancer accounts for the highest proportion of deaths in systemic sclerosis (SSc), exceeding deaths attributed to renal disease and/or infection. Few population-based studies have assessed the burden of cancer in SSc. The present study investigated the association between cancer and SSc using the Clinical Practice Research Datalink (CPRD).

Methods

A validated case ascertainment strategy using combinations of diagnostic Read codes was applied to identify SSc patients in the CPRD with >12 months of data within the time period 01/01/1998 to 31/12/2017. A cohort study design examined cancer occurrence following a diagnosis of SSc. Patients with SSc were matched to six non-SSc comparators by age, sex and GP practice using incident density sampling. Prevalent and incident cases of SSc were analysed separately. Information on date and type of diagnosis of cancer was recorded. Descriptive statistics and Cox analyses determined hazard ratios for cancer occurrence.

Results

From 10.1 million individuals in the CPRD, 1,588 of cases of SSc were identified (85.3% female). We identified 206 cancers that occurred following a diagnosis of SSc (116 in prevalent cohort and 90 amongst incident cohort) (Table). The three commonest cancers were mucocutaneous (4.5%), lung (2.1%) and breast (1.9%). Lung cancer was significantly more common in SSc (Table). Incidence of cancer was higher in SSc (17 vs. 13.8 per 1000 person years) with adjusted hazard ratios of 1.41 (95% CI 1.14-1.75) for prevalent cases and 1.32 (95% CI 1.04-1.67) for incident SSc cases. We did not identify a strong relationship between cancer occurrence and SSc onset. Incidence of cancer increased with age at SSc diagnosis and was higher in males. Death from any cause at 6 months was higher in patients with SSc and cancer.

Conclusion

We have identified an increased risk of cancer occurrence (primarily mucocutaneous and lung) in patients with SSc from the UK, particularly amongst males and patients with higher age at SSc diagnosis. These findings could support screening recommendations for cancer in SSc.

Disclosure

J.D. Pauling: Consultancies; Astra Zenaca, Janssen, Permeatus Inc., Sojournix Pharma, Boehringer Ingelheim. Honoraria; Janssen. Member of speakers’ bureau; Janssen. J. Snowball: None. N. McHugh: None. A. McGrogan: None.
P015 Rheumatology advice lines: how to manage rising demand and limited capacity?
Authors: Hider Samantha , Brownfield Ann , Doe Rebecca , Dutta Shouma , Ryan Sarah
Published: April 2023

Background/Aims

Advice lines services (ALS) are a key aspect of providing coordinated patient care in rheumatology. Demand for rapid access to specialist advice increased during the pandemic due to the disruption of routine outpatient services but it is not clear whether this demand is sustained. We aimed to investigate the changes in demand for ALS, how this varied pre/during COVID-19 and audit the effect upon response times. We also aimed to assess the impact of introducing an email advice service on demand.

Methods

We audited the number of advice line contacts of a single rheumatology department, serving a population of 500,000 people. The telephone adviceline is provided as an answer machine with an email advice service set up in April 2020. The outcome of each contact is recorded as a) advice only b) action required (e.g., prescription, blood test, GP letter) or c) required appointment (monitor/nurse/medical). We audited response times using the RCN guidelines of a two-day response1 as the gold standard.

Results

Demand for advice had been increasing pre-COVID with an average of 368 calls/month (1/1/19-1/7/19) to 420/month (1/7/19-31/12/19). Sixty percent were advice only calls but 27% required additional action. Response times met the audit standard in 97% of cases pre-COVID. During the first two months of COVID demand for advice services doubled, however demand continued to rise although outcomes were similar (Table 1). As the number of contacts increased the proportion of telephone contacts responded to within the audit standard fell. Numbers of email contacts were variable, but response times exceeded the audit standard.

Conclusion

This audit demonstrates the demand of adviceline services has continued to increase throughout the pandemic and beyond, impacting the ability of services to respond within a timely manner. Ongoing QI work is assessing mechanisms to manage increased demand (using healthcare support workers to triage calls) and investigating reasons for accessing ALS to ensure appropriate advice is available.

Disclosure

S. Hider: None. A. Brownfield: None. R. Doe: None. S. Dutta: None. S. Ryan: None.
P022 Successfully using video for DMARD and Biologic patient education
Authors: Penford Rian , Gwynne Catherine , Reith Angela , Wren Elaine , Mackay Kirsten
Published: April 2023

Background/Aims

Patients starting new medications were seen in the Rheumatology department in a F2F group session. This involved 4 nurse led clinics a week, (20-30 patients). It was an efficient way of counselling multiple patients with waiting times approximately 3 weeks. In 2020 the pandemic meant this was no longer possible. The switch to individual telephone education was time consuming.The aim of the digital solution was to educate patients safely, in the most efficient way possible. Delays in starting medication can have an adverse effect on achieving remission of disease and extended use of steroids.

Methods

Members of the Rheumatology team including Secretaries, Clinicians and Pharmacists met to discuss how best to implement this change. Scripts were written for 10 medication videos to reflect the safety advice and administration of each medication. The scripts are a representation of the paper information sent to the patients prior to video education. Patients are sent an email within (24/48hrs of being referred) with a link to the relevant medication video. We asked the patient to email us to say Yes or No that they wanted to start the new medication. Safety screening was completed by the nursing staff and Out Patient Pharmacy delivers the prescription to the patient.

Results

Audit figures May 2020 - April 2022 1038 patients were sent the video medication information. 69 of these patients requested a follow up telephone appointment. Patients satisfaction is recorded with a questionnaire and excellent satisfaction is maintained. Medication education clinics have been reduced from 4 to 1 per week to facilitate the 7% of patients requesting a further appointment. Time has been created to increase capacity for rapid access and follow up appointments.

Conclusion

Videos can be watched by patients friends and family.

FAQ’s e.g “I am taking antibiotics shall I stop my medication?” can be re-watched enhancing future safety. Supporting patient self management and lessening calls to the Rheumatology department.Video Medication Education has revolutionised our practice. Saving time and money whilst maintaining patient safety and satisfaction.

Disclosure

R. Penford: None. C. Gwynne: None. A. Reith: None. E. Wren: None. K. Mackay: None.
P063 COVID shielding stories: co-produced research to understand the voice of people living with arthritis and auto-immune disease
Authors: Sharp Charlotte A , Laidlaw Lynn , Fox Joyce , Sanders Caroline , Morris Rebecca , Dixon William
Published: April 2023

Background/Aims

Up to one-third of people with rheumatological conditions were required to ‘shield’ from COVID-19. This co-produced, qualitative research aimed to understand experiences of the shielding process and the impact of shielding upon people’s lives.

Methods

Adults who shielded due to rheumatological disease participated in audio-recorded interviews and focus groups (FGs). Framework analysis combined inductive and deductive approaches. Creative materials were collected. Two patient contributors proposed the study, are co-investigators, and conducted the research alongside a clinical academic and four-member patient advisory group. COREQ and GRIPP2 guidelines were followed. Full ethical approval was granted by the University of Manchester Research Ethics Committee (2021-11544-20348).

Results

Data were generated from 28 interview and 12 FG participants between October 2021--January 2022. 15 people contributed creative materials. Characteristics included 44/48 (85%) female, ages 18--75 years, non-white 10/48 (21%), all UK regions (Table 1). Corbin & Strauss’s theory, 'Three lines of work: Managing chronic illness', frames the findings. Shielding increased and shifted the burden of ‘illness work’ onto patients, e.g., in gaining access to vaccines and navigating risks and uncertainties due to COVID-19. ‘Life work’ was increased as participants struggled to access food and medicines. Participants’ self-identity was re-appraised in the context of their illness. Many feared for their lives because of their diagnosis for the first time, increasing ‘biographical work’. Participants’ perceived value to society changed over time: feeling equal to the general population at the first UK national lockdown; abandoned by society due to ‘freedom day’ and formal shielding's end. ‘Emotional work’ was added to ‘Three lines of work’. Shielding notification induced fear, stress, devastation, shock and disbelief, balanced by a feeling of being protected. Emotions experienced include anxiety, guilt, anger and frustration. Mental health problems were experienced, often for the first time. Many continued to shield beyond formal shielding's end.

Conclusion

This co-produced, qualitative research highlights experiences and impact of shielding including increased illness, life, biographical and emotional work. Clearer, personalised information would help shielders to understand their risk and vaccine response, informing re-integration into society.

Disclosure

C.A. Sharp: None. L. Laidlaw: None. J. Fox: None. C. Sanders: None. R. Morris: None. W. Dixon: Consultancies; WGD has received consultancy fees from Abbvie and Google, unrelated to this work.
P078 Bone health in men with prostate cancer on androgen deprivation therapy: audit and service development
Authors: Sheng Ziyan , Srivastava Puneet , Shah Jyoti , Yaqub Shahid , Laxminarayan Ramasharan , Ugur Antonia , Williams Simon , Broadhurst Sarah , Tipper Judith , Haynes Charlotte , Hui Michelle
Published: April 2023

Background/Aims

Androgen deprivation therapy (ADT) is commonly used in the treatment of prostate cancer. A significant complication of ADT use is osteoporosis. National and international guidelines recommend a fracture risk assessment (FRA) based on clinical factors and bone mineral density (BMD) to guide bone agent (BA) use and bone protection advice. We audit our current performance, and subsequently offer a novel interdisciplinary service to optimise patients’ bone health.

Methods

Retrospective hospital analysis of patients with metastatic prostate cancer or pre-radiotherapy seen in 2 hospitals over a 6-month period. Patients intended for >6 months treatment were assessed against guideline standards and a retrospective FRA was performed.

Results

82 patients were captured. Age range 62 to 92, median age 77.3. 4.9% patients were already known to the osteoporosis service, but none had been referred for a bone health assessment with the commencement of ADT. Table 1 illustrates our performance against guidelines and the likely need for a BA in a post-hoc analysis at one site. As a result of the collaborative audit undertaken between the urology and osteoporosis services that demonstrated poor recognition of bone health in patients on ADT, the teams worked collaboratively to design a guideline for assessing and managing these patients. This included reviewing the information given to patients about the risk of ADT to bone health, resources that the urology team can signpost patients to, and the initiation of appropriate BA to be undertaken by an appropriately trained person/team.

Conclusion

ADT use can accelerate bone loss, therefore users need FRA and BMD assessments to appropriately guide management. Self-management to optimise bone health by patients can be improved by providing appropriate bone protection advice (regular exercise and adequate vitamin D and calcium intake). Bone health assessments in patients on ADT is a major unmet need that requires attention to minimise clinical risk to patients. The new assessment tool and management pathway in our Trust estimates 114 new patients annually requiring FRA with a maximum number of 372 DXA scans per year accounting for those requiring 2-yearly scans to monitor BMD until the age of 80.

Disclosure

Z. Sheng: None. P. Srivastava: None. J. Shah: None. S. Yaqub: None. R. Laxminarayan: None. A. Ugur: None. S. Williams: None. S. Broadhurst: None. J. Tipper: None. C. Haynes: None. M. Hui: None.
P081 Is it necessary to test vitamin D prior to zoledronate or denosumab treatment?
Authors: Keasley James , Stevens Chloe , Kumar Aman , Sapkota Hem
Published: April 2023

Background/Aims

Prior to each treatment of zoledronate (ZA) or denosumab, it is routine clinical practice to test for vitamin D. If vitamin D levels are low, patients must be started on replacement therapy prior to treatment. Other studies suggest that osteoporosis patients not taking vitamin D supplementation are likely to have subtherapeutic vitamin D levels. Awaiting vitamin D levels can delay timely treatment and organising these tests is labour intensive. In this service evaluation, we examined whether patients could have been treated empirically with vitamin D without testing.

Methods

We included all 542 patients from the New Cross Hospital osteoporosis treatment clinic lists between November 2021 to June 2022. The only patients excluded were those not taking ZA or denosumab. Data collected included demographics, medication history, and vitamin D levels. Vitamin D levels were measured as follows: <15 nmol/L: severe deficiency, 15-30 nmol/L: deficiency, >30-50 nmol/L: insufficiency, >50-250 nmol/L: adequate, >250 nmol/L: potential toxicity.

Results

484 patients were included of which 88.6% were female. The mean age was 76.8. 90.0% were either on vitamin D and calcium supplementation, or on vitamin D supplementation alone. Of these patients on supplementation, vitamin D levels were adequate in 79.8%, insufficient in 7.8%, deficient in 0.4%, severely deficient in 0.2% and not available for the remaining patients. Of those not on supplementation, vitamin D levels were adequate in 45.9%, insufficient in 16.2%, deficient in 10.8% and severely deficient in 4%, and not available for the remaining patients. None of the patients had toxic levels of vitamin D. On contacting the 3 patients prescribed vitamin D supplementation but with deficient or severely deficient vitamin D levels, 2 were not taking the supplements and 1 was taking alfacalcidol (which is not measured in the standard trust vitamin D test). Therefore, of those patients taking vitamin D supplementation as prescribed, their vitamin D levels were all above 30 nmol/L.

Conclusion

This service evaluation therefore supports an approach of not testing vitamin D levels in patients who are due to receive either ZA or denosumab and are taking vitamin D supplementation. A small number of patients taking vitamin D supplementation still had insufficient levels of vitamin D; therefore, it could be recommended to treat all patients on vitamin D supplementation with a short course of high does vitamin D prior to ZA or denosumab treatment. In addition, any patients not taking vitamin D supplementation could also be treated with a course of high dose vitamin D prior to treatment without testing vitamin D levels. This will ensure safe levels of vitamin D and timely treatment of osteoporosis. This will save time and money and reduce waste.

Disclosure

J. Keasley: None. C. Stevens: None. A. Kumar: None. H. Sapkota: None.
P132 A late and rapid increase in ultrasound joint inflammation occurs when anti-CCP positive at-risk individuals with subclinical synovitis progress to inflammatory arthritis
Authors: Harnden Kate , Di Matteo Andrea , Almeida Diogo Esperança , De Lorenzis Enrico , Duquenne Laurence , Garcia-Montoya Leticia , Nam Jacqueline , Emery Paul , Mankia Kulveer
Published: April 2023

Background/Aims

Anti-CCP positive individuals with musculoskeletal (MSK) symptoms and subclinical synovitis on ultrasound (US) are at high risk of developing inflammatory arthritis (IA). Treatment initiation in these individuals is not accepted practice as they do not have clinical synovitis. We aimed to determine whether imaging characteristics change when individuals with pre-RA progress to IA in order to inform the optimal window of opportunity for therapeutic interventions.

Methods

Anti-CCP+ at-risk individuals with MSK symptoms from the Leeds CCP cohort were selected for having US subclinical synovitis [Grey scale (GS)≥1 and Power Doppler (PD)≥1] prior to IA development and an US scan performed at clinical synovitis onset. The US protocol included the metacarpophalangeal joints (MCPJs), proximal interphalangeal joints (PIPJs), wrists, elbows, knees, second-fifth metatarsophalangeal joints (MTPJs), extensor carpi ulnaris (ECU) and finger flexor tendons (FFTs). US PD and GS synovitis were scored semi-quantitatively (0-3) according to EULAR/OMERACT. At patient level, total GS and PD scores were compared between scans. Change on US in the joints that became clinically swollen was also assessed. Wilcoxon signed-rank tests were conducted for comparisons.

Results

Forty-six CCP2+ at-risk individuals were identified (Table). The median US scan interval was 3.5 months (IQR 1.25-8.75). At patient level the overall burden of PD in the joints increased at IA progression, trending towards significance [3 (IQR 1.25-5) vs 4 (IQR 2-7.25) p = 0.063]. Overall burden of GS did not increase. There was an increase in PD in the MCPJs [0 (IQR 0-2) vs 1.5 (IQR0-3) p = 0.008] and MCP and wrist joints combined [1 (IQR 0.25-3) vs 2 (IQR 1.25-4.75) p = 0.002]. GS at the elbows also significantly increased. At joint level PD [1 (IQR(0-2) vs 2 (IQR 0-3) p = 0.036] increased in joints swollen at progression and GS increased with a trend towards significance. Non-swollen joints did not change.

Conclusion

A marked increase in US joint inflammation is seen when CCP+ at-risk individuals with subclinical synovitis on US progress from pre-RA to clinical arthritis. This is particularly evident in the MCPJs, wrist joints and joints that become clinically swollen. Intervening when at-risk individuals have subclinical synovitis may represent a window of opportunity to prevent the rapid increase in joint inflammation which accompanies the onset of joint swelling.

Disclosure

K. Harnden: None. A. Di Matteo: None. D. Esperança Almeida: None. E. De Lorenzis: None. L. Duquenne: None. L. Garcia-Montoya: None. J. Nam: None. P. Emery: None. K. Mankia: None.
P159 Clinical trajectories and predictors of hand function deterioration in systemic sclerosis
Authors: De Lorenzis Enrico , Kakkar Vishal , Di Donato Stefano , Wilson Michelle , Green Lorraine , Alcacer-Pitarch Begonya , Del Galdo Francesco
Published: April 2023

Background/Aims

Hand impairment is a major driver of disability and reduced quality of life in Systemic Sclerosis (SSc) patients. It is multifactorial and the risk and predictability of functional deterioration are unknown. The aim of this study is to describe hand function changes and predictors of functional deterioration in an observational cohort of SSc patients.

Methods

Consecutive SSc patients were longitudinally evaluated every 6 months for 3 years for SSc-related hand involvement. Patient-reported hand symptoms were captured with Cochin Hand Disability Score (CHFS), Raynaud Condition Score (RCS) and overall pain intensity on a visual analogue scale (VAS pain). Their minimal clinical important difference (MCID) and patient-acceptable symptom state (PASS) were evaluated according to validated thresholds. Clinical association with CHFS change over time and 36-month clinically meaningful worsening (MCID-Wor) were assessed via ANOVA and binomial logistic regression, respectively.

Results

One-hundred-seventy-six SSc patients were enrolled in this analysis, 13.6% of them were male and the mean age was 55.1± 12.3 years, the median disease duration was 5.0 years and 31.8% presented a diffuse cutaneous variant. Overall, CHFS worsened over time (p < 0.001); 34.1% of patients reported a clinically significant worsening by the end of follow-up. Accordingly, the proportion of participants reporting CHFS≥PASS increased from 26.1% at baseline to 34.7% at the last follow-up. MCID-W after 36 months was associated with diffuse cutaneous variant [OR 2.44 (95% CI 1.27-4.76), p = 0.008], baseline active-late capillaroscopy pattern [OR 3.00 (95% CI 1.17-7.70), p = 0.013], VAS pain [OR 1.02 (95% CI 1.01-1.03), p = 0.003], RCS [OR 1.03 (95% CI 1.02-1.04), p < 0.001], forearm-hand-finger skin score [OR 1.12 (95% CI 1.00-1.26), p = 0.044], history of digital ulcers [OR 2.39 (95% CI 1.24-4.61), p = 0.008] or flexor contractures [OR 2.52 (95% CI 1.29-4.92), p = 0.007], as well as baseline CHFS [OR 1.03 (95% CI 1.01-1.05), p = 0.001]. A regression model based on these clinical variables could correctly classify 76.7% of cases.

Conclusion

SSc-related hand disability affects more than one-third of patients and tends to worsen over time in both cutaneous subsets despite the current standard of care. Identifying patients at risk of deteriorating hand function should inform targeted intervention strategies to prevent hand disability in SSc.

Disclosure

E. De Lorenzis: None. V. Kakkar: None. S. Di Donato: None. M. Wilson: None. L. Green: None. B. Alcacer-Pitarch: None. F. Del Galdo: Other; FDG received consultancies and research support from Abbvie, AstraZeneca, Boheringer-Ingelheim, Capella, Chemomab, Ergomed, Janssen, Kymab, Mitsubishi-Tanabe.
P188 Measurement of response to treatment in axial spondyloarthritis using quantitative imaging biomarkers: a prospective observational cohort study
Authors: Jones Alexis , Bray Timothy J P , Sakai Naomi , Bainbridge Alain , Ciurtin Coziana , Hall-Craggs Magaret A
Published: April 2023

Background/Aims

Objective assessments of disease activity and response to treatment in axial spondyloarthritis (axSpA) remain a challenge. Diffusion-weighted magnetic resonance imaging (DW-MRI) and chemical shift-encoded MRI (CSE-MRI) inform on bone marrow oedema and fat content and could provide more accurate assessments of disease activity and therapeutic response. This study aims to determine the responsiveness and validity of quantitative imaging biomarkers (QIBs) obtained from DW-MRI and CSE-MRI using the partially-automated Bone Edema and Adiposity Characterisation with Histograms (BEACH) tool in patients with axial spondyloarthritis undergoing biologic therapy.

Methods

Conventional MRI, DWI and CSI was performed on 30 patients with active axSpA at baseline and after 12 - 16 weeks of biologic treatment. Apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) measures were analysed using the BEACH tool. Conventional MR images were assessed using established visual scoring methods. QIBs were assessed in terms of change after treatment and correlation with clinical and conventional MRI measures of disease activity.

Results

There were significant reductions for ADC values, while PDFF-scores showed nonsignificant reductions. Responsiveness to therapy was moderate for ADC measures and comparable to established visual scoring methods for bone marrow oedema. ADC and PDFF correlated well with conventional bone marrow oedema and fatty change scores respectively. Inter-observer variability was lower for QIBs compared with conventional visual scores methods.

Conclusion

ADC measures are sensitive to changes in inflammation in axSpA following biologic therapy and show promise as a biomarker of disease activity in axSpA.

Disclosure

A. Jones: None. T.J.P. Bray: None. N. Sakai: None. A. Bainbridge: None. C. Ciurtin: None. M.A. Hall-Craggs: None.
P201 Inactive Takayasu’s arteritis: a case series analysis of presentations to a tertiary vasculitis centre
Authors: Hanlon Samuel , Nouza Jan , Colquhoun Matthew , Satara Japna , Porter Andrew , Maughan Robert , Youngstein Taryn , Mason Justin
Published: April 2023

Background/Aims

At diagnosis, a proportion of Takayasu’s arteritis (TAK) cases present with imaging evidence consistent with TAK without evidence of active arteritis or systemic disease. Inactive TAK is considered the end-point of a triphasic disease process characterised by a “burnt-out” non-inflammatory fibrotic state. Current EULAR/ACR guidelines recommend immunosuppressive treatment and routine imaging for active TAK but data guiding the management of inactive disease are scarce. The purpose of this case series was to examine baseline characteristics of patients presenting with inactive TAK and investigate disease progression.

Methods

We performed a retrospective review of the Imperial College Takayasu Arteritis Cohort. TAK diagnosis was based on imaging evidence in combination with clinical history. Disease was determined inactive by activity scoring indices (ITAS2010 + NIH) together with inflammatory markers. MR Angiogram (28/30 cases) and CT Angiogram (2/30) were utilised as imaging modalities to determine vascular involvement. Disease distribution was characterised using the Numano Classification (Table 1).

Results

19% (30/158) of patients presented with “inactive disease” at diagnosis. Inactive cases had a median age of diagnosis of 37.8 years, compared to 33.8 in patients with active disease. 48% of inactive cases experienced >2 year delay in reaching diagnosis. Inactive cases did not display significantly elevated inflammatory markers (CRP 3.86, ESR 27.0) at baseline visit and demonstrated arterial lesions on angiography consistent with standard TA definitions in terms of anatomical distribution and characteristics. Inactive patients were followed up with interval MR imaging, allowing us to chart natural disease course without treatment. Of 30 total cases, only five patients developed progression of vascular lesions. Three patients displayed marginal imaging progression without active symptoms together with normal inflammatory markers; these patients did not receive immunosuppression and serial interval imaging demonstrated stable disease, suggesting a non-inflammatory aetiology. Two patients developed progression attributed to active disease, necessitating treatment with immunosuppression.

Conclusion

A significant proportion of patients have inactive disease at TAK diagnosis. This presents a challenge to the treating clinician and further uncertainty for patients. This case study provides evidence that cases of burnt-out TAK can be managed safely without immunosuppressive treatment using routine imaging surveillance and serum biomarkers.

Disclosure

S. Hanlon: None. J. Nouza: None. M. Colquhoun: None. J. Satara: None. A. Porter: None. R. Maughan: None. T. Youngstein: None. J. Mason: None.
P202 A study on myocardial dysfunction in Indian patients with Takayasu's arteritis
Authors: Bajaj Rohit , Ghosh Shounak , Tanna Dhaval , Yadavalli Durgarao , Kazi Wasim , Singal Vinay , Gupta Rajiva
Published: April 2023

Background/Aims

Takayasu’s arteritis (TA) is a form of predominantly large vessel vasculitis affecting young individuals. Signs of vascular insufficiency or systemic inflammation may be seen in the vast majority of patients, with cardiac involvement noted in more than one-third of the cases. Previous histopathologic studies from India have revealed the presence of myocarditis in up to 50% of patients. We conducted this study to assess myocardial dysfunction using Speckle Tracking Echocardiography (STE), a novel method to assess global longitudinal systolic strain (GLSS), in TA patients and healthy controls.

Methods

This was a cross-sectional, case-control study. Between August 2018 and May 2021, all consenting adult patients classified as per the ACR 1990 Criteria as Takayasu’s arteritis were included in the study after taking their informed consent. Age and gender-matched healthy controls without known comorbidities like hypertension, diabetes, or coronary artery disease were included for comparison. Demographic, clinical, and laboratory parameters were assessed. All enrolled participants underwent 2D echocardiography with speckle tracking and GLSS evaluation as well as B-mode ultrasonography to measure carotid intimal medial thickness (CIMT) of bilateral carotid arteries, by a single, blinded cardiologist with over 20 years of experience in his field. The study was approved by the Institutional Ethics Committee.

Results

Fifty patients with TA who consented to the study were included, with fifty healthy controls. 66% of the cohort were female. TA patients had significantly lower mean LVEF (56% vs 60%, p < 0.0001), worse mean GLSS (-19.3% vs -20.9%, p = 0.003), more patients with GLSS >-19.7 (48% vs 24%, p = 0.01), and higher mean CIMT values (0.58mm vs 0.44mm, p = 0.001) than the healthy controls. Cases with GLSS less negative than -19.7% (24 out of 50) were significantly older (mean age 42.8 vs 35.4 years, p = 0.049), had more cardiac (62.5% vs 19.2%, p = 0.02) and coronary artery involvement (37.5% vs 7.7%, p = 0.011). Mean CIMT values were significantly more in patients with active disease as per the ITAS 2010 score. GLSS could not differentiate between active and inactive disease, nor did they correlate with raised inflammatory markers. There was no significant correlation between higher CIMT values and worse GLSS.

Conclusion

This is a pilot study comparing TA cases with healthy controls using STE and CIMT values. While mean CIMT values and GLSS were increased in patients with TA, GLSS did not correlate with disease activity status. Older age and a greater proportion of patients with cardiac involvement were the only significant differences noted in patients with worse GLSS. Longitudinal studies based on STE may help us document changes in subclinical myocarditis in TA.

Disclosure

R. Bajaj: None. S. Ghosh: None. D. Tanna: None. D. Yadavalli: None. W. Kazi: None. V. Singal: None. R. Gupta: None.