Clinical and functional characterisation of a novel TNFRSF1A c.605T > A/V173D cleavage site mutation associated with tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), cardiovascular complications and excellent response to etanercept treatment.

Objectives: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site. Methods: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFa in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS. Results: TNFRSF1A sequencing disclosed a novel V173D/ p.Val202Asp substitution encoded by exon 6 in one family, the c.194–14G.A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFa-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC. Conclusions: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients

The building materials’ and components’ database for an evidences-based design approach

The design process has always to meet, since the preliminary approaching step, every specific requirement which is foreseen for the building to realize. In a certain way, this operation represents an every time different prototype which varies according to the design demands for the considered room and the carried function, but also according to the used building materials: such an approach is already difficult by itself, but if we consider that at present the availability of technical information about building materials, components and systems is often incomplete or lost among many documents or even absent, it is evident that the designer’s activity becomes very uneven. That is the reason why, the definition of a database for building materials in which indicating each informative attribute to be considered becomes fundamental in order to: - provide a correct, univocal, clear and complete information for every building stakeholder; - help manufacturers to individualize the real needed information to join to their products, so to allow an easier comparison among products themselves and, as a consequence, to push towards a better quality of the entire building process (improving production, design, but also management). The paper deals with an analysis of the necessary information for designers and for maintenance planners, providing different levels of deepening according to the intended use. A particular attention will be paid on the so called “evidences-based design” which gives the opportunity to point out and to consider the most meaningful design matters, making an aware choice of building materials, components and systems. The International Service Life Data Base developed by CSTB with Politecnico di Milano will be reported as a tool for service life prediction, and buildings’ management

BIM AND GIS INTEGRATION FOR INFRASTRUCTURE ASSET MANAGEMENT: A BIBLIOMETRIC ANALYSIS

The integration of Building Information Modelling (BIM) and Geographical Information Systems (GIS) is gaining momentum in digital built Asset Management (AM), and has the potential to improve information management operations and provide advantages in process control and delivery of quality AM services, along with underlying data management benefits through entire life cycle of an asset. Work has been carried out relating GeoBIM/AM to buildings as well as infrastructure assets, where the potential financial savings are extensive. While information form BIM maybe be sufficient for building-AM; for infrastructure AM a combination of GIS and BIM is required. Scientific literature relating to this topic has been growing in recent years and has now reached a point where a systematic analysis of current and potential uses of GeoBIM in AM for Infrastructure is possible. Three specific areas form part of the analysis – a review of BIM and Infrastructure AM and GIS and Infrastructure AM leads to a better understanding of current practice. Combining the two, a review of GeoBIM and Infrastructure AM allows the benefits of, and issues relating to, GeoBIM to be clearly identified, both at technical and operational levels. A set of 54 journal articles was selected for in-depth contents analysis according to the AM function addressed and the managed asset class. The analysis enabled the identification of three categories of issues and opportunities: data management, interoperability and integration and AM process and service management. The identified knowledge gaps, in turn, underpin problem definition for the next phases of research into GeoBIM for infrastructure AM

Impact of COVID-19 pandemic on the management of patients with RA: a survey of rheumatologists in six European countries

OBJECTIVE: We aimed to describe, from the perspective of rheumatologists in Europe, how the coronavirus disease 2019 (COVID-19) pandemic has impacted their management of people with RA and the continuing medical education of physicians. METHODS: Rheumatologists participating in the Adelphi RA Disease Specific ProgrammeTM in six European countries were contacted in August and September 2020 for a telephone survey. Rheumatologists were asked seven attitudinal questions on changes to patient management, prescription behaviour and continuing education owing to COVID-19. Results were summarized with descriptive statistics. RESULTS: The telephone survey was completed by 284 rheumatologists. The most commonly reported changes to patient management were increased utilization of video/telephone consultations (66.5% of respondents), fewer visits (58.5%) and limiting physical contact (58.1%). Furthermore, 67.9% of rheumatologists who indicated that prescribing behaviour had changed switched their patients to self-administered medication, and 60.7% reported not starting patients on targeted synthetic DMARDs, biologic originator DMARDs or biosimilar DMARDs. In total, 57.6% of rheumatologists believed that changes in management would persist. Rheumatologists reported that 38.0% of patients expressed concerns about how COVID-19 would impact treatment, including access to treatment and the risk of infection. The biggest impact on rheumatologist education was a switch to online training and conferences. CONCLUSION: All countries saw changes in patient management and prescribing behaviour, including the rapid uptake of telemedicine. It is important that the international rheumatology community learns from these experiences to prepare better for future pandemics and to address ongoing rheumatologist shortages

Disease stratification in giant cell arteritis to reduce relapses and prevent long-term vascular damage

For years, clinicians and researchers working on giant cell arteritis have been battling with the conundrum of a disease that displays a short-term steroid responsiveness but is burdened by a remarkable risk of flares and chronic damage in the long term. This issue should be addressed by a change in the direction of research and clinical practice. Evidence suggests that giant cell arteritis is not a monolithic disease; it varies in extent and severity. Hence, treatment should be guided by disease stratification. The current one-size-fits-all strategy leads to overreliance on glucocorticoids and progression of glucocorticoid-related and disease-related complications. A new approach requires disease stratification using clinical, laboratory, histology, and imaging parameters. A giant cell arteritis registry might offer opportunities to scrutinise disease course and prognostic variables early; however, more studies that directly incorporate disease stratification through the above parameters are required. This Series paper also suggests that future clinical trials should be targeted at patients with different disease strata of giant cell arteritis and should incorporate ultrasound, PET-CT scanning, and other imaging modalities as key outcomes

What is a response in randomised controlled trials in giant cell arteritis?

Glucocorticoids (GCs) are the gold standard for treatment of giant cell arteritis (GCA); however, there is a need for studies on GC-sparing agents, given that up to 85% of patients receiving GC only develop adverse events. Previous randomised controlled trials (RCTs) have applied different primary endpoints, limiting the comparison of treatment effects in meta-analyses and creating an undesired heterogeneity of outcomes. The harmonisation of response assessment is therefore an important unmet need in GCA research. In this viewpoint article, we discuss the challenges and opportunities with the development of new, internationally accepted response criteria. A change of disease activity is a fundamental component of response; however, it is debatable whether the ability to taper GC and/or the maintenance of a disease state for a specific time period, as applied in recent RCTs, should be part of response assessment. The role of imaging and novel laboratory biomarkers as possible objective markers of disease activity needs further investigation but might be a possibility when drugs directly or indirectly influence the levels of traditional acute-phase reactants such as erythrocyte sedimentation rate and C reactive protein. Futures response criteria might be constructed as a multidomain set, but the questions about which domains will be included and what their relative weights will be still need to be answered.Pathophysiology and treatment of rheumatic disease

Assessment of the face validity, feasibility and utility of a patient-completed questionnaire for polymyalgia rheumatica: a postal survey using the QQ-10 questionnaire.

BACKGROUND: The development of a patient-reported outcome measure (PROM) for polymyalgia rheumatica (PMR), a condition that causes pain, stiffness and disability, is necessary as there is no current validated disease-specific measure. Initial literature synthesis and qualitative research established a conceptual framework for the condition along with a list of symptoms and effects of PMR that patients felt were important to them. These findings were used to derive the candidate items for a patient-completed questionnaire. We aim to establish the face validity of this initial "long form" of a PROM. METHODS: People with a current or previous diagnosis of PMR were recruited both from the community and from rheumatology clinics. They were asked to complete the PMR questionnaire along with the QQ-10 questionnaire, which is a measure used to assess the face validity, feasibility and utility of patient healthcare questionnaires. RESULTS: A total of 28 participants with an age range of 59-85 years and a length of time since diagnosis from 4 months to 18 years completed the QQ-10. The overall mean "value" score was 79% (SD 12), and the mean "burden" score was 21% (SD 18). The free-text comments were analysed thematically and were found to focus on layout, content, where in the clinical pathway the questionnaire would be most beneficial, specific items missing and other areas for consideration. CONCLUSIONS: The high mean value score and low burden score indicate that the questionnaire has good face validity and is acceptable to patients. The questionnaire now needs to undergo further psychometric evaluation and refinement to develop the final tool for use in clinical practice and research

Determination of glomerular filtration rate “en passant” after high doses of iohexol for computed tomography in intensive care medicine—a proof of concept

Accurate assessment of renal function is of great clinical and scientific importance, as it is an important pharmacokinetic covariate of pivotal drugs. The iohexol clearance is nearly identical to the glomerular filtration rate, but its determination usually requires an intravenous injection and therefore bears intrinsic risks. This motivates to showcase an “en passant” approach to quantification of renal function without additional risk or blood sampling beyond routine care using real-world data. We enrolled 37 intensive care patients who received high doses of iohexol for computed tomography imaging, and quantified series of iohexol plasma concentrations by high-performance liquid chromatography (HPLC-UV). Iohexol clearance was derived by both log-linear regression and nonlinear least squares fitting and compared to glomerular filtration rate estimated by the CKD-EPI-2021 formulas. Nonlinear fitting not only turned out to be more accurate but also more robust in handling the irregularly timed data points. Concordance of iohexol clearance against estimations based on both creatinine and cystatin C showed a slightly higher bias (−3.44 mL/min/1.73 m2) compared to estimations based on creatinine alone (−0.76 mL/min/1.73 m2), but considerably narrower limits of agreement (±42.8 vs. 56 mL/min/1.73 m2) and higher Lin’s correlation (0.84 vs. 0.72). In summary, we have demonstrated the feasibility and performance of the “en passant” variant of the iohexol method in intensive care medicine and described a working protocol for its application in clinical practice and pharmacologic studies

A rating system for building resilience

Measuring and rating resilience of assets is a key enabler for asset and portfolio management. This paper presents a resilience rating system for buildings by utilising a Building Information Modelling approach. The assessment is carried out through a calculation following the Analytical Hierarchy Process. This methodology can be applied to different types of buildings, without a loss of precision or reliability. This resilience rating forms an integral part of more comprehensive array of Key Performance Indicators frameworks for asset and portfolio management, and therefore can significantly influence strategic investment choices for designers, engineers and building owners

Imaging in diagnosis, monitoring and outcome prediction of large vessel vasculitis: a systematic literature review and meta-analysis informing the 2023 update of the EULAR recommendations

Objectives To update the evidence on imaging for diagnosis, monitoring and outcome prediction in large vessel vasculitis (LVV) to inform the 2023 update of the European Alliance of Associations for Rheumatology recommendations on imaging in LVV. Methods Systematic literature review (SLR) (2017–2022) including prospective cohort and cross-sectional studies (>20 participants) on diagnostic, monitoring, outcome prediction and technical aspects of LVV imaging. Diagnostic accuracy data were meta-analysed in combination with data from an earlier (2017) SLR. Results The update retrieved 38 studies, giving a total of 81 studies when combined with the 2017 SLR. For giant cell arteritis (GCA), and taking clinical diagnosis as a reference standard, low risk of bias (RoB) studies yielded pooled sensitivities and specificities (95% CI) of 88% (82% to 92%) and 96% (95% CI 86% to 99%) for ultrasound (n=8 studies), 81% (95% CI 71% to 89%) and 98% (95% CI 89% to 100%) for MRI (n=3) and 76% (95% CI 67% to 83%) and 95% (95% CI 71% to 99%) for fluorodeoxyglucose positron emission tomography (FDG-PET, n=4), respectively. Compared with studies assessing cranial arteries only, low RoB studies with ultrasound assessing both cranial and extracranial arteries revealed a higher sensitivity (93% (95% CI 88% to 96%) vs 80% (95% CI 71% to 87%)) with comparable specificity (94% (95% CI 83% to 98%) vs 97% (95% CI 71% to 100%)). No new studies on diagnostic imaging for Takayasu arteritis (TAK) were found. Some monitoring studies in GCA or TAK reported associations of imaging with clinical signs of inflammation. No evidence was found to determine whether imaging severity might predict worse clinical outcomes. Conclusion Ultrasound, MRI and FDG-PET revealed a good performance for the diagnosis of GCA. Cranial and extracranial vascular ultrasound had a higher pooled sensitivity with similar specificity compared with limited cranial ultrasound