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Background/Aims Fracture Liaison Service (FLS) is labour intensive. It aims to identify all patients aged over 50 years presenting with a new fragility fracture and assess for treatment, in order to prevent future fractures and associated morbidity and mortality. According to the Royal Osteoporosis Society published Standards (2015), patients should have a comprehensive bone assessment within 3 months of the incident fracture. However, such assessments are time consuming, typically taking up to 40 minutes of an FLS practitioner's time. Understaffing led to designing an approach to gather information and streamline the Fracture Liaison service. Methods We approached an electronics communication company who generated a secure form containing the information required for FLS initial assessment. As a trial, all patients identified by the FLS as having a new fragility fracture between 15th November 2021 and 15th December 2021 were sent a text link to this questionnaire. A follow-up message was sent 1 day and 1 week later (3 messages in total). The questionnaires were then exported to the patient's electronic clinical record. Data collected included information allowing prediction of risk for future fractures. Following assessment of this data, action letters could be sent to the GP advising on a treatment plan, for example, to start an oral bisphosphonate or referral for parenteral treatment. We analysed the results and performed cost analysis based on comparison to normal practice where the initial assessment would have been undertaken as a clinic appointment. Results 43 out of 103 patients (42%) responded to the questionnaire. Of these 43 patients, 32 (74%) were female and the majority aged 60 to 79 years. Our cost analysis showed that allowing for a 30-minute face to face appointment for each of 43 patients would have taken 22.5 hours. By comparison, virtual assessment of the data from each questionnaire took only 8 minutes ie a total of 5.7 hours. This saved 16.8 hours of the FLS practitioner's time with a calculated cost saving of £352, based on professional time cost of £21 per hour. Face to face attendances would have cost £120 per patient ie £5160 for 43 patients. The total amount saved using the electronic questionnaire for 43 patients was £5512. Conclusion We were able to capture the initial FLS bone assessment data using an electronic questionnaire in 43 out of 103 patents. This resulted in a significant cost saving from outpatient clinics of £5512 over a 1-month period. Downstream processing of the data was much shorter. Further action will be to modify the text messages to increase yield of patients. Electronic fracture liaison is effective at reducing demands on the service and coordinating activity. We have demonstrated a significant cost saving on a small number of patients. Disclosure R. Reid: None. E. Lever: None. D. Davis: None.

Evaluation of FRalpha expression by tumor cell lines

Table of Patient Characteristics

IgE antibodies are key mediators of antiparasitic immune responses, but their potential for cancer treatment via antibody-dependent cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen–specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages; however, the underlying therapeutic mechanisms were undefined and in vivo proof of concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fcϵ receptor system for cancer studies. We also generated rat IgE and IgG mAbs specific for the folate receptor (FRα), which is expressed widely on human ovarian tumors, along with a syngeneic rat tumor model expressing human FRα. Compared with IgG, anti-FRα IgE reduced lung metastases. This effect was associated with increased intratumoral infiltration by TNFα+ and CD80+ macrophages plus elevated TNFα and the macrophage chemoattractant MCP-1 in lung bronchoalveolar lavage fluid. Increased levels of TNFα and MCP-1 correlated with IgE-mediated tumor cytotoxicity by human monocytes and with longer patient survival in clinical specimens of ovarian cancer. Monocytes responded to IgE but not IgG exposure by upregulating TNFα, which in turn induced MCP-1 production by monocytes and tumor cells to promote a monocyte chemotactic response. Conversely, blocking TNFα receptor signaling abrogated induction of MCP-1, implicating it in the antitumor effects of IgE. Overall, these findings show how antitumor IgE reprograms monocytes and macrophages in the tumor microenvironment, encouraging the clinical use of IgE antibody technology to attack cancer beyond the present exclusive reliance on IgG. Cancer Res; 77(5); 1127–41. ©2017 AACR.

Description of additional experiments and procedures carried out in this study

Objectives The Covid-19 pandemic necessitated a rapid global transition towards telemedicine; yet much remains unknown about telemedicine’s acceptability and safety in rheumatology. To help address this gap and inform practice, this study investigated rheumatology patient and clinician experiences and views of telemedicine. Methods Sequential mixed methodology combined analysis of surveys and in-depth interviews. Between and within-group differences in views of telemedicine were examined for patients and clinicians using t-tests. Results Surveys (patients n = 1340, clinicians n = 111) and interviews (patients n = 31, clinicians n = 29) were completed between April 2021 and July 2021. The majority of patients were from the UK (96%) and had inflammatory arthritis (32%) or lupus (32%). Patients and clinicians rated telemedicine as worse than face-to-face consultations in almost all categories, although >60% found it more convenient. Building trusting medical relationships and assessment accuracy were great concerns (93% of clinicians and 86% of patients rated telemedicine as worse than face-to-face for assessment accuracy). Telemedicine was perceived to have increased misdiagnoses, inequalities and barriers to accessing care. Participants reported highly disparate telemedicine delivery and responsiveness from primary and secondary care. Although rheumatology clinicians highlighted the importance of a quick response to flaring patients, only 55% of patients were confident that their rheumatology department would respond within 48 hours. Conclusion Findings indicate a preference for face-to-face consultations. Some negative experiences may be due to the pandemic rather than telemedicine specifically, although the risk of greater diagnostic inaccuracies using telemedicine is unlikely to be fully resolved. Training, choice, careful patient selection, and further consultation with clinicians and patients is required to increase telemedicine’s acceptability and safety. Trial registration This telemedicine study is part of a pre-registered longitudinal multi-stage trial, the LISTEN study (ISRCTN-14966097), with later Covid-related additions registered in March 2021, including a pre-registered statistical analysis plan.

Objective To better understand rheumatology patient and clinician pandemic-related experiences, medical relationships and behaviours in order to help identify the persisting impacts of the COVID-19 pandemic and inform efforts to ameliorate the negative impacts and build upon the positive ones. Methods Rheumatology patients and clinicians completed surveys (patients n = 1543, clinicians n = 111) and interviews (patients n = 41, clinicians n = 32) between April 2021 and August 2021. A cohort (n = 139) of systemic autoimmune rheumatic disease patients was also followed up from March 2020 to April 2021. Analyses used sequential mixed methods. Pre-specified outcome measures included the Warwick–Edinburgh Mental wellbeing score (WEMWBS), satisfaction with care and healthcare behaviours. Results We identified multiple ongoing pandemic-induced/increased barriers to receiving care. The percentage of patients agreeing they were medically supported reduced from 74.4% pre-pandemic to 39.7% during-pandemic. Ratings for medical support, medical security and trust were significantly (P Conclusion Without concerted action—such as rebuilding trust, improved administrative systems and more support for clinicians—barriers to care and negative impacts of the pandemic on trust, medical relationships, medical security and patient help-seeking may persist in the longer term. Trial registration This study is part of a pre-registered longitudinal multi-stage trial, the LISTEN study (ISRCTN-14966097), with later COVID-related additions registered in March 2021, including a pre-registered statistical analysis plan.

Systemic lupus erythematosus (SLE) is a remarkable condition characterised by diversity amongst its clinical features and immunological abnormalities. In this review, we attempt to capture the major immunological changes linked to the pathophysiology of lupus and discuss the challenge it presents in moving towards the concept of precision medicine. Currently broadly similar types of drugs, e.g., steroids, immunosuppressives, hydroxychloroquine are used to treat many of the diverse clinical features of SLE. We suspect that, as the precise immunopathological abnormalities differ between the various organs/systems in lupus patients, it will be some time before precision medicine can be fully applied to SLE.

Objective The shielding guidance in the UK for the clinically extremely vulnerable (CEV) commenced on 23 March 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic. The purpose of this study was to explore the impact of the pandemic and shielding on patients with lupus and related systemic autoimmune rheumatic diseases (SARDs). Methods This was a mixed-methods cohort study (n = 111) including pre-lockdown baseline surveys (March 2020), follow-up surveys (June 2020) and in-depth interviews during July 2020 (n = 25). Results Most participants had a high level of anxiety regarding their mortality risk from COVID-19 and supported the concept of shielding. Shielding allocations and communications were perceived as inconsistently applied and delivered. More than half of those not classified as CEV reported feeling abandoned, at increased risk and with no support. Shielding communications increased feelings of being ‘cared about’, but also increased fear, and the ‘vulnerable’ labelling was perceived by some to damage social and self-identity. More than 80% of those classified as CEV stated that the classification and subsequent communications had changed their social-mixing behaviour. Despite many negative impacts of COVID-19 and shielding/lockdown being identified, including isolation, fear and reduced medical care, the quantitative data during the pandemic showed increases in most measures of wellbeing (which was low at both time points) from pre-lockdown, including reductions in the impact of fatigue and pain (P-values Conclusion Shielding classifications and communications were, in general, viewed positively, although they were perceived as inconsistently delivered and anxiety-provoking by some participants. More frequent positively framed communication and wellbeing support could benefit all SARD patients. Slower-paced lockdown lifestyles might confer health/wellbeing benefits for some people with chronic diseases.

Objective The aim was to explore the self-reported impact of the COVID-19 pandemic on changes to care and behaviour in UK patients with systemic autoimmune rheumatic diseases, to help ensure that patient experiences are considered in future pandemic planning. Methods This was a longitudinal mixed methods study, with a cohort completing baseline surveys in March 2020 and follow-up surveys in June 2020 (n = 111), combined with thematic analysis of the LUPUS UK forum and participant interviews (n = 28). Results Cancellations of routine care and difficulties in accessing medical support contributed to some participants deteriorating physically, including reports of hospitalizations. The majority of participants reported that fear of COVID-19 and disruptions to their medical care had also adversely impacted their mental health. Feeling medically supported during the pandemic was correlated with multiple measures of mental health and perceptions of care, including the Warwick–Edinburgh mental well-being score (r = 0.44, P = 0.01). Five themes were identified: detrimental reduction in care; disparities in contact and communication (medical security vs abandonment sub-theme); perceived and actual endangerment; the perfect storm of reduced clinician ability to help and increased patient reticence to seek help; and identifying the patients most vulnerable to reduced medical care. Conclusion The diversion of resources away from chronic disease care was perceived by many participants to have caused adverse outcomes. Fear about increased vulnerability to COVID-19 was high, contributing to health-care-avoidant behaviours. This study also highlights the influence of clinician accessibility and patients feeling medically supported on multiple measures of physical and mental health.

Objective The aim was to explore the impact of patient–physician interactions, pre- and post-diagnosis, on lupus and UCTD patients’ psychological well-being, cognition and health-care-seeking behaviour. Methods Participants were purposively sampled from the 233 responses to a survey on patient experiences of medical support. Twenty-one semi-structured interviews were conducted and themes generated using thematic analysis. Results The study identified six principal themes: (i) the impact of the diagnostic journey; (ii) the influence of key physician(s) on patient trust and security, with most participants reporting at least one positive medical relationship; (iii) disparities in patient–physician priorities, with patients desiring more support with quality-of-life concerns; (iv) persisting insecurity and distrust, which was prevalent and largely influenced by previous and anticipated disproportionate (often perceived as dismissive) physician responses to symptoms and experiences of widespread inadequate physician knowledge of systemic autoimmune diseases; (v) changes to health-care-seeking behaviours, such as curtailing help-seeking or under-reporting symptoms; and (vi) empowerment, including shared medical decision-making and knowledge acquisition, which can mitigate insecurity and improve care. Conclusion Negative medical interactions pre- and post-diagnosis can cause a loss of self-confidence and a loss of confidence and trust in the medical profession. This insecurity can persist even in subsequent positive medical relationships and should be addressed. Key physicians implementing empowering and security-inducing strategies, including being available in times of health crises and validating patient-reported symptoms, might lead to more trusting medical relationships and positive health-care-seeking behaviour.

Systemic lupus erythematosus (SLE) is a remarkable condition characterised by diversity amongst its clinical features and immunological abnormalities. In this review, we attempt to capture the major immunological changes linked to the pathophysiology of lupus and discuss the challenge it presents in moving towards the concept of precision medicine. Currently broadly similar types of drugs, e.g., steroids, immunosuppressives, hydroxychloroquine are used to treat many of the diverse clinical features of SLE. We suspect that, as the precise immunopathological abnormalities differ between the various organs/systems in lupus patients, it will be some time before precision medicine can be fully applied to SLE.

Background The crowned dens syndrome is a rare presentation of Calcium pyrophosphate deposition disease. It is characterised by severe acute or recurrent neck pain associated with headache, fever and elevated inflammatory markers. CT usually demonstrates calcium pyrophosphate crystal deposition in the suspensory ligaments adjacent to the atlanto-axial joint. We are reporting a series of four patients presenting with sudden onset of neck pain and raised inflammatory makers over a 9 month period. Objectives To raise awareness of crowned-dens syndrome, its clinical presentation, radiographic findings and management. Methods Four patients’ electronic patient records including history, clinical findings and treatment were reviewed. Imaging was discussed at a rheumatology/radiology multi-disciplinary meeting. Results Four patients (2 female, 2 male) aged between 64 and 86 years presented with severe neck pain and stiffness. In all cases the onset of symptoms was less than a week prior to presentation and was associated with greatly restricted mobility. 2 patients had associated headache, arthralgia and myalgia. All patients had normal tone, power, reflexes and sensation on neurological examination. There was no pyrexia. Inflammatory markers were markedly raised with CRP ranging from 90-343 mg/L at presentation (Table 1). One patient had a neutrophilia. CT scan of the head was performed in each case and showed no evidence of subarachnoid haemorrhage, space occupying lesion or meningeal enhancement. PET-CT scan in all patients showed intense uptake around the atlanto-axial joint as well as calcification of the ligaments. All patients were commenced on a reducing regime of prednisolone starting at 40mg daily, tapering to 0mg over 6 weeks. Symptoms and inflammatory markers reduced on induction of steroids. Two patients suffered a relapse on reducing steroids and required further higher doses of steroid. Conclusion Patients presenting with acute neck pain, headache and raised inflammatory markers require evaluation for an infective aetiology. Pyrophosphate disease of the atlanto-axial joint however, appears to be an increasingly recognised cause of this presentation. Awareness by acute physicians, rheumatologists and radiology colleagues is important, as the condition can be misdiagnosed as Giant Cell Arteritis, Polymyalgia Rheumatica or meningitis; in order to avoid unnecessary investigations and delay in initiating the appropriate treatment. The condition is steroid responsive. References [1] Heck A, Nolan N, Rojas-Moreno C, Crowned Dens Syndrome: Calcium Pyrophosphate Deposition Disease Masquerading as Osteomyelitis. J Rheumatol. 2018Oct;45(10):1422-1423 [2] Ledingham D, Cappelen-Smith C, Cordato D, Crowned dens syndrome. Pract Neurol. 2018Feb;18(1):57-59 [3] Tagami S, Inokuchi R, Awaji K, Maehara H, Yamaguchi Y, Nakajima S, Crowned dens syndrome and interspinous ligament inflammation due to calcium pyrophosphate deposition in an elderly man. Spine J. 2016Jul;16(7):e453-4 Disclosure of Interests None declared

A 68-year-old man presented to the eye clinic with a 3–4-week history of pain in the left eye, which he had noted to be red for the past 12 months. There was no systemic upset. Fig [1][1] shows injection of the sclera, scleromalacia and ulceration, threatening perforation of the eye. Blood testing

IgE antibodies are key mediators of antiparasitic immune responses, but their potential for cancer treatment via antibody-dependent cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen–specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages; however, the underlying therapeutic mechanisms were undefined and in vivo proof of concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fcϵ receptor system for cancer studies. We also generated rat IgE and IgG mAbs specific for the folate receptor (FRα), which is expressed widely on human ovarian tumors, along with a syngeneic rat tumor model expressing human FRα. Compared with IgG, anti-FRα IgE reduced lung metastases. This effect was associated with increased intratumoral infiltration by TNFα+ and CD80+ macrophages plus elevated TNFα and the macrophage chemoattractant MCP-1 in lung bronchoalveolar lavage fluid. Increased levels of TNFα and MCP-1 correlated with IgE-mediated tumor cytotoxicity by human monocytes and with longer patient survival in clinical specimens of ovarian cancer. Monocytes responded to IgE but not IgG exposure by upregulating TNFα, which in turn induced MCP-1 production by monocytes and tumor cells to promote a monocyte chemotactic response. Conversely, blocking TNFα receptor signaling abrogated induction of MCP-1, implicating it in the antitumor effects of IgE. Overall, these findings show how antitumor IgE reprograms monocytes and macrophages in the tumor microenvironment, encouraging the clinical use of IgE antibody technology to attack cancer beyond the present exclusive reliance on IgG. Cancer Res; 77(5); 1127–41. ©2017 AACR.

Activation of the major histocompatibility complex (MHC) by interferon-gamma (IFN-γ) is a fundamental step in the adaptive immune response to pathogens. Here, we show that reorganization of chromatin loop domains in the MHC is evident within the first 30 min of IFN-γ treatment of fibroblasts, and that further dynamic alterations occur up to 6 h. These very rapid changes occur at genomic sites which are occupied by CTCF and are close to IFN-γ-inducible MHC genes. Early responses to IFN-γ are thus initiated independently of CIITA, the master regulator of MHC class II genes and prepare the MHC for subsequent induction of transcription.

The functional significance of changes in nuclear structure and organization in transformed cells remains one of the most enigmatic questions in cancer biology. In this review, we discuss relationships between nuclear organization and transcription in terms of the three-dimensional arrangement of genes in the interphase cancer nucleus and the regulatory functions of nuclear matrix proteins. We also analyse the role of nuclear topology in the generation of gene fusions. We speculate that this type of multi-layered analysis will one day provide a framework for a more comprehensive understanding of the genetic origins of cancer and the identification of new therapeutic targets.

The folding of chromatin into topologically constrained loop domains is essential for genomic function. We have identified genomic anchors that define the organization of chromatin loop domains across the human major histocompatibility complex (MHC). This locus contains critical genes for immunity and is associated with more diseases than any other region of the genome. Classical MHC genes are expressed in a cell type-specific pattern and can be induced by cytokines such as interferon-gamma (IFNG). Transcriptional activation of the MHC was associated with a reconfiguration of chromatin architecture resulting from the formation of additional genomic anchors. These findings suggest that the dynamic arrangement of genomic anchors and loops plays a role in transcriptional regulation.

Specific attachment of chromosomal sites to the nuclear matrix is crucial to the control of transcription and DNA replication., Although the principles governing chromosomal architecture are largely unresolved, there is evidence that higher-order chromatin folding is mediated by the anchoring of specific DNA sequences to the nuclear matrix. These genome anchors are also crucial regulators of gene expression and DNA replication, and play a role in pathogenesis.