Granulocyte-macrophage colony-stimulating factor neutralisation in patients with axial spondyloarthritis in the UK (NAMASTE): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis. METHODS: This proof-of-concept, randomised, double-blind, placebo-controlled, phase 2, Bayesian (NAMASTE) trial was done at nine hospitals in the UK. Participants aged 18-75 years with axial spondyloarthritis, meeting the Assessment in SpondyloArthritis international Society (ASAS) criteria and the ASAS-defined MRI criteria, with active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), were eligible. Those who had inadequately responded or had intolerance to previous treatment with an anti-TNF agent were included. Participants were randomly assigned (6:1) to receive subcutaneous namilumab 150 mg or placebo at weeks 0, 2, 6, and 10. Participants, site staff (except pharmacy staff), and central study staff were masked to treatment assignment. The primary endpoint was the proportion of participants who had an ASAS ≥20% improvement (ASAS20) clinical response at week 12 in the full analysis set (all randomly assigned participants). This trial is registered with ClinicalTrials.gov (NCT03622658). FINDINGS: From Sept 6, 2018, to July 25, 2019, 60 patients with moderate-to-severe active axial spondyloarthritis were assessed for eligibility and 42 were randomly assigned to receive namilumab (n=36) or placebo (n=six). The mean age of participants was 39·5 years (SD 13·3), 17 were women, 25 were men, 39 were White, and seven had previously received anti-TNF therapy. The primary endpoint was not met. At week 12, the proportion of patients who had an ASAS20 clinical response was lower in the namilumab group (14 of 36) than in the placebo group (three of six; estimated between-group difference 6·8%). The Bayesian posterior probability η was 0·72 (>0·927 suggests high clinical significance). The rates of any treatment-emergent adverse events in the namilumab group were similar to those in the placebo group (31 vs five). INTERPRETATION: Namilumab did not show efficacy compared with placebo in patients with active axial spondyloarthritis, but the treatment was generally well tolerated. FUNDING: Izana Bioscience, NIHR Oxford Biomedical Research Centre (BRC), NIHR Birmingham BRC, and Clinical Research Facility.

Advanced Imaging of Gout and Other Inflammatory Diseases Around the Knee.

The knee is one of the most commonly affected joints in the course of inflammatory arthropathies, such as crystal-induced and autoimmune inflammatory arthritis. The latter group includes systemic connective tissue diseases and spondyloarthropathies. The different pathogenesis of these entities results in their varied radiologic images. Some lead quickly to joint destruction, others only after many years, and in the remaining, destruction will not be a distinguishing radiologic feature.Radiography, ultrasonography, and magnetic resonance imaging have traditionally been the primary modalities in the diagnosis of noninflammatory and inflammatory arthropathies. In the case of crystallopathies, dual-energy computed tomography has been introduced. Hybrid techniques also offer new diagnostic opportunities. In this article, we discuss the pathologic findings and imaging correlations for crystallopathies and inflammatory diseases of the knee, with an emphasis on recent advances in their imaging diagnosis.

Current Role of Conventional Radiography of Sacroiliac Joints in Adults and Juveniles with Suspected Axial Spondyloarthritis: Opinion from the ESSR Arthritis and Pediatric Subcommittees.

This opinion article by the European Society of Musculoskeletal Radiology Arthritis and Pediatric Subcommittees discusses the current use of conventional radiography (CR) of the sacroiliac joints in adults and juveniles with suspected axial spondyloarthritis (axSpA). The strengths and limitations of CR compared with magnetic resonance imaging (MRI) and computed tomography (CT) are presented.Based on the current literature and expert opinions, the subcommittees recognize the superior sensitivity of MRI to detect early sacroiliitis. In adults, supplementary pelvic radiography, low-dose CT, or synthetic CT may be needed to evaluate differential diagnoses. CR remains the method of choice to detect structural changes in patients with suspected late-stage axSpA or established disease and in patients with suspected concomitant hip or pubic symphysis involvement. In children, MRI is the imaging modality of choice because it can detect active as well as structural changes and is radiation free.

Interdisciplinary consensus statements on imaging of DRUJ instability and TFCC injuries.

OBJECTIVES: The purpose of this agreement was to establish evidence-based consensus statements on imaging of distal radioulnar joint (DRUJ) instability and triangular fibrocartilage complex (TFCC) injuries by an expert group using the Delphi technique. METHODS: Nineteen hand surgeons developed a preliminary list of questions on DRUJ instability and TFCC injuries. Radiologists created statements based on the literature and the authors' clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panelists consisted of twenty-seven musculoskeletal radiologists. The panelists scored their degree of agreement to each statement on an 11-item numeric scale. Scores of "0," "5," and "10" reflected complete disagreement, indeterminate agreement, and complete agreement, respectively. Group consensus was defined as a score of "8" or higher for 80% or more of the panelists. RESULTS: Three of fourteen statements achieved group consensus in the first Delphi round and ten statements achieved group consensus in the second Delphi round. The third and final Delphi round was limited to the one question that did not achieve group consensus in the previous rounds. CONCLUSIONS: Delphi-based agreements suggest that CT with static axial slices in neutral rotation, pronation, and supination is the most useful and accurate imaging technique for the work-up of DRUJ instability. MRI is the most valuable technique in the diagnosis of TFCC lesions. The main indication for MR arthrography and CT arthrography are Palmer 1B foveal lesions of the TFCC. CLINICAL RELEVANCE STATEMENT: MRI is the method of choice for assessing TFCC lesions, with higher accuracy for central than peripheral abnormalities. The main indication for MR arthrography is the evaluation of TFCC foveal insertion lesions and peripheral non-Palmer injuries. KEY POINTS: • Conventional radiography should be the initial imaging technique in the assessment of DRUJ instability. CT with static axial slices in neutral rotation, pronation, and supination is the most accurate method for evaluating DRUJ instability. • MRI is the most useful technique in diagnosing soft-tissue injuries causing DRUJ instability, especially TFCC lesions. • The main indications for MR arthrography and CT arthrography are foveal lesions of the TFCC.

Arterial embolization during percutaneous vertebroplasty resulting in bilateral renal infarcts and ischemic colitis.

This case report documents an arterial embolic event that occurred during vertebroplasty for a pathological compression fracture of T12 in a 54-year-old female with known metastatic breast carcinoma. A CT angiogram performed after the procedure demonstrated cement migration into the aorta, both kidneys, and the inferior mesenteric artery and its branches, with ischemic colitis involving the descending colon and sigmoid colon. A CT scan 4 months post-procedure demonstrated resolution of the colitis. Neovascularity and cortical destruction in malignant bone lesions are thought to contribute to arterial cement leak.

Imaging of the Long Head of Biceps Tendon and Rotator Interval.

This article reviews the imaging and common pathology of the long head of biceps tendon and rotator interval (RI). This area of complex anatomy plays a crucial role in normal shoulder function. Injury or abnormality of the RI may contribute to a range of shoulder pathology, such as biceps instability, tendinopathy, and frozen shoulder. Understanding the normal and pathologic appearances of the RI structures is crucial for a correct diagnosis and directing treatment.

Ultrasound-guided continuous radiofrequency ablation of the suprascapular nerve for chronic shoulder pain secondary to osteoarthritis: a retrospective cohort study.

OBJECTIVES: The objective of this study is to retrospectively evaluate the use of ultrasound-guided continuous radiofrequency (CRF) lesioning of the suprascapular nerve for treating chronic shoulder pain, due to osteoarthritis. We describe a modified distal and selective ablation technique in the spinoglenoid notch, with motor and sensory stimulation, which protects the motor branch of the nerve from ablation. METHODS: A retrospective analysis was performed of patients, who underwent ultrasound-guided CRF lesioning of the suprascapular nerve from October 2013 to January 2020. During the procedure, the CRF electrode is placed in the spinoglenoid notch, at the distal suprascapular nerve capsular branch. Motor and sensory stimulations are used to confirm the position. CRF lesioning is applied up to three times, at 3 different points, for 1 min each time, at 80° C. RESULTS: In total, 127 first CRF suprascapular nerve lesioning procedures were performed on 101 patients with chronic shoulder pain secondary to osteoarthritis. One hundred nineteen diagnostic ultrasound-guided suprascapular nerve corticosteroid injections were performed prior to ablation. Mean pre-injection Visual Analogue Scale pain score (VAS) was 8.3, with post-injection VAS score of 4.4 at 24 h and 4.5 at 2 weeks. Mean pre-CRF lesioning VAS pain score was 7.7 with post-CRF lesioning VAS score of 4.4 at 24 h and 4.5 at 2 weeks. CONCLUSIONS: Ultrasound-guided CRF lesioning of the suprascapular nerve in the spinoglenoid notch is a safe treatment for chronic osteoarthritic shoulder pain, with repeat treatments infrequently required. It is associated with significant improvement in VAS pain scores. KEY POINTS: • Ultrasound-guided continuous radiofrequency lesioning of the suprascapular nerve in the spinoglenoid notch is a safe treatment for chronic shoulder pain in degenerative disease, with repeat treatments infrequently required. • The procedure is performed under ultrasound guidance, without the use of ionising radiation.

Presurgical Perspective and Postsurgical Evaluation of the Diabetic Foot.

Management of the diabetic foot is complex and challenging, requiring a multidisciplinary approach. Imaging plays an important role in the decision-making process regarding surgery. This article discusses the presurgical perspective and postsurgical evaluation of the diabetic foot.

Association between hip joint impingement and lumbar disc disease in elite rowers.

OBJECTIVES: Lumbar disc disease is a known cause of back pain. Increasingly it is thought that cam morphology of the hip may have a causal role in development of lumbar disc disease. The aim of this study was to describe the morphology of the hip and investigate the association of cam morphology with lumbar disc disease observed on MRI in elite rowers. METHODS: Cross-sectional observational study of 20 elite rowers (12 male, 8 female, mean age 24.45, SD 2.1). Assessment included clinical examination, questionnaires, 3T MRI scans of the hips and lumbar spine. Alpha angle of the hips and Pfirrmann score of lumbar discs were measured. RESULTS: 85% of rowers had a cam morphology in at least one hip. Alpha angle was greatest at the 1 o'clock position ((bone 70.9 (SD 16.9), cartilage 71.4 (16.3)). 95% of the group were noted to have labral tears, but only 50% of the group had history of groin pain. 85% of rowers had at least one disc with a Pfirrmann score of 3 or more and 95% had a history of back pain. A positive correlation was observed between the alpha angle and radiological degenerative disc disease (correlation coefficient=3.13, p=0.012). A negative correlation was observed between hip joint internal rotation and radiological degenerative disc disease (correlation coefficient=-2.60, p=0.018). CONCLUSIONS: Rowers have a high prevalence of labral tears, cam morphology and lumbar disc disease. There is a possible association between cam morphology and radiological lumbar degenerative disc disease, however, further investigation is required.

Ex Vivo and In Vivo Evaluation of Dodecaborate-Based Clusters Encapsulated in Ferumoxytol Nanoparticles.

Host-guest interactions represent a growing research area with recent work demonstrating the ability to chemically manipulate both host molecules as well as guest molecules to vary the type and strength of bonding. Much less is known about the interactions of the guest molecules and hybrid materials containing similar chemical features to typical macrocyclic hosts. This work uses in vitro and in vivo kinetic analyses to investigate the interaction of closo-dodecahydrododecaborate derivatives with ferumoxytol, an iron oxide nanoparticle with a carboxylated dextran coating. We find that several boron cluster derivatives can become encapsulated into ferumoxytol, and the lack of pH dependence in these interactions suggests that ion pairing, hydrophobic/hydrophilic interaction, and hydrogen bonding are not the driving force for encapsulation in this system. Biodistribution experiments in BALB/c mice show that this system is nontoxic at the reported dosage and demonstrate that encapsulation of dodecaborate-based clusters in ferumoxytol can alter the biodistribution of the guest molecules.

The Musculoskeletal Manifestations of Marfan Syndrome: Diagnosis, Impact, and Management.

PURPOSE OF REVIEW: Marfan syndrome (MFS) is an autosomal dominant heritable disorder of fibrillin-1 (FBN1) with predominantly ocular, cardiovascular, and musculoskeletal manifestations that has a population prevalence of approximately 1 in 5-10,000 (Chiu et al. Mayo Clin Proc. 89(1):34-42, 146, Dietz 3, Loeys et al. J Med Genet. 47(7):476-85, 4). RECENT FINDINGS: The vascular complications of MFS still pose the greatest threat, but effective management options, such as regular cardiac monitoring and elective surgical intervention, have reduced the risk of life-threatening cardiovascular events, such as aortic dissection. Although cardiovascular morbidity and mortality remains high, these improvements in cardiovascular management have extended the life expectancy of those with MFS by perhaps 30-50 years from an estimated mean of 32 years in 1972 (Dietz 3, Gott et al. Eur J Cardio-thoracic Surg. 10(3):149-58, 147, Murdoch et al. N Engl J Med. 286(15):804-8, 148). The musculoskeletal manifestations of MFS, which to date have received less attention, can also have a significant impact on the quality of life and are likely to become more important as the age of the Marfan syndrome population increases (Hasan et al. Int J Clin Pract. 61(8):1308-1320, 127). In addition, musculoskeletal manifestations are often critically important in the diagnosis of MFS. Here, we review the main clinically relevant and diagnostically useful musculoskeletal features of MFS, which together contribute to the "systemic features score" (referred to hereafter as systemic score), part of the revised Ghent nosology for MFS. We discuss current treatment strategies and highlight the need for a multidisciplinary approach to diagnosis and management. Finally, we review new pharmacological approaches that may be disease modifying and could help to improve the outcome for individuals with this syndrome.

Impact of the COVID-19 pandemic on corticosteroid injection services: A National Survey of Members of the British Society of Skeletal Radiologists (BSSR).

OBJECTIVE: To describe the restructuring of services by British radiologists in response to evolving national guidelines and highlight the impact of the COVID-19 pandemic on the treatment of musculoskeletal (MSK) conditions. METHODS: An online anonymised survey was distributed via the British Society of Skeletal Radiology (BSSR) members forum in November 2020. Responses were collated using a standardised Google form including 21 questions. RESULTS: 135 members of the BSSR completed the survey. 85% of respondents stopped performing corticosteroid injections (CSI) during the initial lockdown of the pandemic. This was primarily influenced by national guidelines. The majority of respondents initially abstained from offered CSI procedures, then by November 2020, 69% of respondents were providing CSI for high and low risk patients, 23% were only providing CSI for low-risk patients with 8% still not performing any CSI. 40% of respondents reported routinely obtaining specific written consent regarding the risk of COVID-19. Approximately, 11,000 CSI were performed by respondents between March and November 2020 with no reported significant COVID-19-related complications. Over 80% of BSSR members reported that the number of CSI procedures that they performed dropped by more than 80% compared to usual. 73% of respondents reported an increased backlog of patients awaiting treatment. The average waiting time for routine outpatient CSI treatment was > 12 weeks in 53% of responses, compared to 34% the previous year. CONCLUSION: The COVID-19 pandemic has had a significant impact on the clinical practices of MSK radiologists in the UK. Our survey highlights the rapid response of BSSR members as national guidelines evolved. Currently, the majority of respondents are performing CSI for musculoskeletal conditions when clinically indicated, with enhanced consent. However, the pandemic has resulted in increased waiting times - delaying the treatment of patients who may be suffering with significant pain and disability. Further research is warranted to provide guidance around both service recovery and provision of CSI around COVID-19 vaccination schedules. ADVANCES IN KNOWLEDGE: BSSR members responded rapidly to changing guidelines during the COVID-19 pandemic. The majority of respondents are currently performing CSI when clinically indicated. The pandemic has resulted in a significant increase in waiting times which will have a significant impact on UK musculoskeletal services.

Interdisciplinary consensus statements on imaging of scapholunate joint instability.

OBJECTIVES: The purpose of this agreement was to establish evidence-based consensus statements on imaging of scapholunate joint (SLJ) instability by an expert group using the Delphi technique. METHODS: Nineteen hand surgeons developed a preliminary list of questions on SLJ instability. Radiologists created statements based on the literature and the authors' clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panellists consisted of twenty-seven musculoskeletal radiologists. The panellists scored their degree of agreement to each statement on an eleven-item numeric scale. Scores of '0', '5' and '10' reflected complete disagreement, indeterminate agreement and complete agreement, respectively. Group consensus was defined as a score of '8' or higher for 80% or more of the panellists. RESULTS: Ten of fifteen statements achieved group consensus in the second Delphi round. The remaining five statements achieved group consensus in the third Delphi round. It was agreed that dorsopalmar and lateral radiographs should be acquired as routine imaging work-up in patients with suspected SLJ instability. Radiographic stress views and dynamic fluoroscopy allow accurate diagnosis of dynamic SLJ instability. MR arthrography and CT arthrography are accurate for detecting scapholunate interosseous ligament tears and articular cartilage defects. Ultrasonography and MRI can delineate most extrinsic carpal ligaments, although validated scientific evidence on accurate differentiation between partially or completely torn or incompetent ligaments is not available. CONCLUSIONS: Delphi-based agreements suggest that standardized radiographs, radiographic stress views, dynamic fluoroscopy, MR arthrography and CT arthrography are the most useful and accurate imaging techniques for the work-up of SLJ instability. KEY POINTS: • Dorsopalmar and lateral wrist radiographs remain the basic imaging modality for routine imaging work-up in patients with suspected scapholunate joint instability. • Radiographic stress views and dynamic fluoroscopy of the wrist allow accurate diagnosis of dynamic scapholunate joint instability. • Wrist MR arthrography and CT arthrography are accurate for determination of scapholunate interosseous ligament tears and cartilage defects.

Hand Masses.

Hand and wrist soft tissue masses may be classified as pseudotumors, benign neoplasms, or malignant neoplasms. The vast majority of hand lesions are benign. Consideration of the location of the lesion and its imaging characteristics often leads to a specific diagnosis. Pseudotumors discussed in this article are ganglion cysts, accessory muscles, and inflammatory lesions. True tumors are described according to their tissue type: nerve sheath tumors, adipocytic tumors, so-called fibrohistiocytic tumors, pericytic tumors, and vascular lesions. We also outline the imaging features of masses encountered in the hand and wrist.

Rheumatoid Hand and Other Hand-deforming Rheumatic Conditions.

The hand and wrist are commonly involved in rheumatic conditions, particularly rheumatoid arthritis and other systemic connective tissue diseases. With spondyloarthritis, hand and wrist involvement frequently occurs in psoriatic arthritis but generally does not occur in the remaining subtypes. The hand and wrist may also be affected in various metabolic and endocrine diseases, but these lie beyond the scope of this review.Radiographs may demonstrate the presence of joint space narrowing, bone loss, cysts and erosions, malalignments, and osteolysis. They may also show regions of soft tissue swelling or thinning, and detect calcifications. Ultrasonography and magnetic resonance imaging (MRI) enable evaluation of the soft tissues, particularly the synovium, tenosynovium, and tendons. Furthermore, erosions are better demonstrated than on radiographs. MRI allows evaluation of periarticular bone marrow edema.This article discusses typical imaging features of the hand and wrist in rheumatologic conditions including the advantages and limitations of the various methods.

Aneurysmal bone cysts in the spine, causing neurological compromise: safety and clinical efficacy of sclerotherapy utilizing sodium Tetradecyl sulfate foam.

OBJECTIVE: To assess the clinical efficacy, technical feasibility, and safety profile of percutaneous sclerotherapy utilizing sodium tetradecyl-sulfate foam (STS) as a first-line treatment strategy for aggressive spinal aneurysmal bone cysts (sABCs) presenting with neurological compromise. MATERIALS AND METHODS: Between July 2013 and September 2019, eight consecutive patients (5 males; 3 females; mean age 22±17, range 7-52) underwent fluoroscopic/CT-guided intraosseous sclerotherapy for sABCs. Pain and/or neurological compromise was the primary indications. Procedural data, complications, imaging, and clinical results were analyzed. RESULTS: Technical success was achieved in all cases. Mean procedure time was 25±15 min (range 6-167); 1 to 5 repeat treatment cycles (mean 3.7±1.2) utilizing a mean 2.6mls±1.3 (range 1-6) of agitated 3% STS, with a DLP mean dose of 158±91 mGy*cm (range 62-331) per procedure. One reported a minor complication (pain), but no significant complications. Two patients had persistent neurological deficit due to cord compression despite successful sclerotherapy, requiring surgical resection (and were thereby excluded from the final outcome analysis). The remaining six patients demonstrated a significant reduction in tumor volume (p = 0.028), pain (p = 0.027), and SINS (spinal instability neoplastic score) (p = 0.027) at up to 5 years of follow-up (mean 20 ± 16.7, range 7-51 months). CONCLUSION: Percutaneous sclerotherapy with STS is a minimally invasive, technically feasible, safe, and effective first-line treatment for primary sABCs causing pain and neurological compromise, alleviating the need for extensive surgery. It is most effective with three or more treatment cycles, in patients with higher SINS, pain scores, or tumor volumes at the initial presentation.

[Differential diagnoses of inflammatory hip joint]. / Differenzialdiagnosen des entzündlichen Hüftgelenks.

The differential diagnoses of inflammatory hip diseases play an important role for the diagnosis of hip pain. The radiological manifestations of rheumatic inflammatory hip pain with the corresponding use of imaging modalities were dealt in part 1 of the CME article. In this second part a systematic approach is explained in order to differentiate the many rheumatic diseaeses from degeneration, synovial tumors and infections. The interpretation of the pathologies seen in imaging in association with the clinical phenotype is more precisely elucidated for the individual differential diagnoses. The concomitant occurrence of different diseases, sometimes as secondary complications, has a substantial influence on treatment planning and should be recognized by radiologists.

Diagnostic accuracy of ultrasound and magnetic resonance imaging in detecting Stener lesions of the thumb: systematic review and meta-analysis.

This study assesses the diagnostic accuracy of ultrasound and magnetic resonance imaging (MRI) in diagnosing Stener lesions of the thumb. MEDLINE, PubMed, Embase and Cochrane CENTRAL were searched for studies using ultrasound or MRI to detect Stener lesions following suspected thumb ulnar collateral ligament injuries. The reference standard was surgical exploration or clinical joint stability. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A random-effects bivariate meta-analysis was used to estimate pooled sensitivity and specificity. Forest plots were generated. Nine ultrasound (315 thumbs) and six MRI (107 thumbs) studies were included in meta-analysis (all high risk of bias). Pooled sensitivity and specificity for ultrasound were 95% and 94%, and for MRI were 93% and 98%. Both ultrasound and MRI demonstrate high diagnostic accuracy in detecting Stener lesions. Ultrasound is an appropriate first-line imaging modality.

[Inflammatory changes of the hip joint]. / Entzündliche Veränderungen des Hüftgelenks.

Most cases of hip pain in adults are related to osteoarthrosis, thus other causes, e.g. inflammation, are often not adequately considered for the joint pain in the initial diagnosis. This review article describes the various rheumatic diseases of the hip in the context of diagnostic image interpretation. The advantages and disadvantages of the individual imaging modalities are discussed against the background of pathological findings of rheumatological diseases of the hip.