Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus

Figure S2. Daratumumab has no impact on T cells and monocytes ex vivo. (A) Total number of CD3+ T cells in each daratumumab concentration at 72 h post-treatment. (B) Quantification of CD38 MFI on CD3+ T cells at 72 h post-culture with isotype control or daratumumab at indicated concentrations. (C) Total number of CD14+ monocytes in each daratumumab concentration at 72 h post-treatment. (D) Quantification of CD38 MFI on CD14+ monocytes at 72 h post-culture with isotype control or daratumumab at indicated concentrations. Data shown represent four patients with SLE, six with RA and six healthy control donors. (PNG 2127 kb

Clinical practice guidelines for the foot and ankle in rheumatoid arthritis: a critical appraisal

Background: Clinical practice guidelines are recommendations systematically developed to assist clinical decision-making and inform healthcare. In current rheumatoid arthritis (RA) guidelines, management of the foot and ankle is under-represented and the quality of recommendation is uncertain. This study aimed to identify and critically appraise clinical practice guidelines for foot and ankle management in RA. Methods: Guidelines were identified electronically and through hand searching. Search terms 'rheumatoid arthritis', 'clinical practice guidelines' and related synonyms were used. Critical appraisal and quality rating were conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: Twenty-four guidelines were included. Five guidelines were high quality and recommended for use. Five high quality and seven low quality guidelines were recommended for use with modifications. Seven guidelines were low quality and not recommended for use. Five early and twelve established RA guidelines were recommended for use. Only two guidelines were foot and ankle specific. Five recommendation domains were identified in both early and established RA guidelines. These were multidisciplinary team care, foot healthcare access, foot health assessment/review, orthoses/insoles/splints, and therapeutic footwear. Established RA guidelines also had an 'other foot care treatments' domain. Conclusions: Foot and ankle management for RA features in many clinical practice guidelines recommended for use. Unfortunately, supporting evidence in the guidelines is low quality. Agreement levels are predominantly 'expert opinion' or 'good clinical practice'. More research investigating foot and ankle management for RA is needed prior to inclusion in clinical practice guidelines

Plantar plate pathology is associated with erosive disease in the painful forefoot of patients with rheumatoid arthritis

Background: Disease-related foot pathology is recognised to have a significant impact on mobility and functional capacity in the majority of patients with rheumatoid arthritis (RA). The forefoot is widely affected and the metatarsophalangeal (MTP) joints are the most common site of symptoms. The plantar plates are the fibrocartilaginous distal attachments of the plantar fascia inserting into the five proximal phalanges. Together with the transverse metatarsal ligament they prevent splaying of the forefoot and subluxation of the MTP joints. Damage to the plantar plates is a plausible mechanism therefore, through which the forefoot presentation, commonly described as ‘walking on pebbles’, may develop in patients with RA. The aims of this study were to investigate the relationship between plantar plate pathology and clinical, biomechanical and plain radiography findings in the painful forefoot of patients with RA. Secondly, to compare plantar plate pathology at the symptomatic lesser (2nd-5th) MTP joints in patients with RA, with a group of healthy age and gender matched control subjects without foot pain. Methods: In 41 patients with RA and ten control subjects the forefoot was imaged using 3T MRI. Intermediate weighted fat-suppressed sagittal and short axis sequences were acquired through the lesser MTP joints. Images were read prospectively by two radiologists and consensus reached. Plantar plate pathology in patients with RA was compared with control subjects. Multivariable multilevel modelling was used to assess the association between plantar plate pathology and the clinical, biomechanical and plain radiography findings. Results: There were significant differences between control subjects and patients with RA in the presence of plantar plate pathology at the lesser MTP joints. No substantive or statistically significant associations were found between plantar plate pathology and clinical and biomechanical findings. The presence of plantar plate pathology was independently associated with an increase in the odds of erosion (OR = 52.50 [8.38–326.97], p < 0.001). Conclusion: The distribution of plantar plate pathology at the lesser MTP joints in healthy control subjects differs to that seen in patients with RA who have the consequence of inflammatory disease in the forefoot. Longitudinal follow-up is required to determine the mechanism and presentation of plantar plate pathology in the painful forefoot of patients with RA

Guidelines for the management of people with foot health problems related to rheumatoid arthritis: a survey of their use in podiatry practice

Background: In the last decade there has been a significant expansion in the body of knowledge on the effects of rheumatoid arthritis (RA) on the foot and the management of these problems. Aligned with this has been the development of specialist clinical roles for podiatrists. However, despite being recommended by national guidelines, specialist podiatrists are scarce. In order to inform non-specialist podiatrists of the appropriate interventions for these foot problems, management guidelines have been developed and disseminated by a group of specialist podiatrists. The aim of this survey was to investigate the use of these guidelines in clinical practice. Method: Following ethical approval an online questionnaire survey was carried out. The questions were formulated from a focus group and comprised fixed response and open response questions. The survey underwent cognitive testing with two podiatrists before being finalised. An inductive approach using thematic analysis was used with the qualitative data. Results: 245 questionnaires were completed (128 – non-specialist working in the private sector, 101 non – specialists working in the NHS and 16 specialist podiatrists). Overall, 97% of the non-specialists (n = 222) had not heard of the guidelines. The non-specialists identified other influences on their management of people with RA, such as their undergraduate training and professional body branch meetings. Three main themes emerged from the qualitative data: (i) the benefits of the foot health management guidelines, (ii) the barriers to the use of guidelines generally and (iii) the features of useable clinical guidelines. Conclusions: This study has revealed some crucial information about podiatrists ’ level of engagement with the foot health management guidelines and the use of guidelines in general. Specifically, the non-specialist podiatrists were less likely to use the foot health management guidelines than the specialist podiatrists. The positive aspects were that for the specialist practitioners, the guidelines helped them to identify their professional development needs and for the few non-specialists that did use them, they enabled appropriate referral to the rheumatology team for foot health management. The barriers to their use included a lack of understanding of the risk associated with managing people with RA and that guidelines can be too long and detailed for use in clinical practice. Suggestionsare made for improving the implementation of foot health guidelines

Quantitative label-free characterisation and discrimination of osteoarthritis and rheumatoid arthritis based on hyperspectral autofluorescence features

Pain is currently assessed using subjective measurements, often not aligning with clinical symptoms. Therefore, objective pain level assessments, using minimally-invasive and molecular methods, are needed to assess disease activity and response to treatment in osteoarthritis and rheumatoid arthritis. We report sophisticated quantitative biochemical “signatures” from the label-free hyperspectral imaging (HSI) of cartilage tissue for the characterization of molecular composition, structure and functional status. Further study on sinuvium tissue provides evidence that HSI could be used as a novel technique to delineate disease state. Additionally, HSI could be used to objectively separate individuals based on pain severity providing molecular correlates of pai

Native T1 mapping in transthyretin amyloidosis

Objectives The aims of the study were to explore the ability of native myocardial T1 mapping by cardiac magnetic resonance to: 1) detect cardiac involvement in patients with transthyretin amyloidosis (ATTR amyloidosis); 2) track the cardiac amyloid burden; and 3) detect early disease. Background ATTR amyloidosis is an underdiagnosed cause of heart failure, with no truly quantitative test. In cardiac immunoglobulin light-chain amyloidosis (AL amyloidosis), T1 has high diagnostic accuracy and tracks disease. Here, the diagnostic role of native T1 mapping in the other key type of cardiac amyloid, ATTR amyloidosis, is assessed. Methods A total of 3 groups were studied: ATTR amyloid patients (n = 85; 70 males, age 73 ± 10 years); healthy individuals with transthyretin mutations in whom standard cardiac investigations were normal (n = 8; 3 males, age 47 ± 6 years); and AL amyloid patients (n = 79; 55 males, age 62 ± 10 years). These were compared with 52 healthy volunteers and 46 patients with hypertrophic cardiomyopathy (HCM). All underwent T1 mapping (shortened modified look-locker inversion recovery); ATTR patients and mutation carriers also underwent cardiac 3,3-diphosphono-1,2- propanodicarboxylicacid (DPD) scintigraphy. Results T1 was elevated in ATTR patients compared with HCM and normal subjects (1,097 ± 43 ms vs. 1,026 ± 64 ms vs. 967 ± 34 ms, respectively; both p &lt; 0.0001). In established cardiac ATTR amyloidosis, T1 elevation was not as high as in AL amyloidosis (AL 1,130 ± 68 ms; p = 0.01). Diagnostic performance was similar for AL and ATTR amyloid (vs. HCM: AL area under the curve 0.84 [95% confidence interval: 0.76 to 0.92]; ATTR area under the curve 0.85 [95% confidence interval: 0.77 to 0.92]; p &lt; 0.0001). T1 tracked cardiac amyloid burden as determined semiquantitatively by DPD scintigraphy (p &lt; 0.0001). T1 was not elevated in mutation carriers (952 ± 35 ms) but was in isolated DPD grade 1 (n = 9, 1,037 ± 60 ms; p = 0.001). Conclusions Native myocardial T1 mapping detects cardiac ATTR amyloid with similar diagnostic performance and disease tracking to AL amyloid, but with lower maximal T1 elevation, and appears to be an early disease marker