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Background Psoriatic arthritis with inflammatory axial involvement (PsA-ax) and axial spondyloarthritis (axSpA) are distinct entities within the spectrum of spondyloarthritides. Despite overlapping clinical and imaging features, the extent and pattern of radiographic spinal progression in PsA-ax relative to axSpA remain insufficiently characterized. Objective To describe and analyse differences in radiographic spinal progression between axSpA and PsA-ax. Methods In this retrospective cohort study, 246 patients (axSpA: n=172; PsA-ax: n=74) with lateral radiographs of the cervical, thoracic, and/or lumbar spine were included. Radiographic progression was quantified using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). An adjusted linear mixed-effects model was used to analyse differences in the longitudinal association with mSASSS between axSpA and PsA-ax. The estimated β-coefficient along with the 95% confidence interval (CI) is reported. Results The mSASSS differed substantially at baseline, averaging 6 (SD 14) in axSpA and 0.96 (SD 2.12) in PsA-ax. The patient-level mean MSASSS change over 2 years was small overall, but higher in patients with axSpA than in those with PsA-ax, averaging 0.39 (SD 1.83) and 0.07 (SD 0.29), respectively. A total of 27% of axSpA and 5% of PsA-ax had a patient-level mean MSASSS change over 2 years >0 units. In the adjusted linear mixed-effects model, the estimated mean progression in mSASSS over two years was slightly lower in PsA-ax compared to axSpA (adjusted β = -0.088, 95% CI: -0.446 to 0.271). Conclusion Patients with PsA-ax were found to have slightly lower mean progression in mSASSS over two years than patients with axSpA. However, the wide CI crossing zero indicates large uncertainty and compatibility with no difference in mSASSS progression between PsA with axial involvement and axSpA, warranting further studies.

Objective To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis (RA). Methods We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. Results Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate κ values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). Conclusions US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA.

ObjectivesPatients under rituximab therapy are at high risk for a severe COVID-19 disease course. Humoral immune responses to SARS-CoV-2 vaccination are vastly diminished in B-cell-depleted patients, even after a third vaccine dose. However, it remains unclear whether these patients benefit from a fourth vaccination and whether continued rituximab therapy affects antibody development.MethodsIn this open-label extension trial, 37 rituximab-treated patients who received a third dose with either a vector or mRNA-based vaccine were vaccinated a fourth time with an mRNA-based vaccine (mRNA-1273 or BNT162b2). Key endpoints included the humoral and cellular immune response as well as safety after a fourth vaccination.ResultsThe number of patients who seroconverted increased from 12/36 (33%) to 21/36 (58%) following the fourth COVID-19 vaccination. In patients with detectable antibodies to the spike protein’s receptor-binding domain (median: 8.0 binding antibody units (BAU)/mL (quartiles: 0.4; 13.8)), elevated levels were observed after the fourth vaccination (134.0 BAU/mL (quartiles: 25.5; 1026.0)). Seroconversion and antibody increase were strongly diminished in patients who received rituximab treatment between the third and the fourth vaccination. The cellular immune response declined 12 weeks after the third vaccination, but could only be slightly enhanced by a fourth vaccination. No unexpected safety signals were detected, one serious adverse event not related to vaccination occurred.ConclusionsA fourth vaccine dose is immunogenic in a fraction of rituximab-treated patients. Continuation of rituximab treatment reduced humoral immune response, suggesting that rituximab affects a second booster vaccination. It might therefore be considered to postpone rituximab treatment in clinically stable patients.Trial registration number2021-002348-57.

ObjectiveTo assess the humoral response to messenger RNA (mRNA) vaccine of patients with systemic autoimmune rheumatic disease (SARD) and the effect of immunosuppressive medication in a matched cohort study.MethodsPatients with SARD were enrolled and matched 1:1 for sex and age with healthy control (HC) subjects. Differences in humoral response to two doses of an mRNA vaccine in terms of seroconversion rate (SCR) and SARS-CoV-2 antibody level between the two groups and the impact of treatment within patients with SARD were assessed.ResultsWe enrolled 82 patients with SARD and 82 matched HC. SCR after the first dose was lower among the patient group than that of HC (65% compared with 100% in HC, p<0.0001) but levelled up after the second dose (94% vs 100%). After the second dose, SCR was lower for patients on combination disease-modifying antirheumatic drug (DMARD) therapy compared with all other groups (81% compared with 95% for monotherapy, p=0.01; 100% for both no DMARD therapy and HC, both p<0.0001). In addition, antibody levels after both doses were lower in patients compared with HC. We found that vaccination response was determined primarily by the number of DMARDs and/or glucocorticoids received, with patients receiving combination therapy (dual and triple therapy) showing the poorest response.ConclusionsPatients with SARD showed a good response after the second vaccination with an mRNA vaccine. However, the choice of immunosuppressive medication has a marked effect on both SCR and overall antibody level, and the number of different immunomodulatory therapies determines vaccination response.

Objectives and designTo further elucidate the effects of rare systemic autoimmune rheumatic diseases (SARD) and their treatment on antibody development after vaccination against SARS-CoV-2, we compared patients with and without immunosuppressive therapy to healthy controls in an observational cohort study.Participants and settingWe enrolled 52 patients with SARD and 72 healthy subjects in a prospective, observational study at the Medical University of Vienna and measured the humoral response 6 months after two mRNA vaccinations and 2–6 weeks after a third dose.ResultsPatients with vasculitis showed significantly (p=0.02) lower antibody titres 6 months after vaccination (median 247 BAU/mL, IQR [185–437]), as compared with healthy controls (median 514 BAU/mL, [185–437], IQR 323; 928, vasculitis patients: 247, IQR [185; 437], p<0.05). Patients receiving 2–3 immunomodulatory medications showed significantly lower antibody levels. Of note, all patients with SARD, even those without immunomodulatory medication, developed lower antibody levels after the third dose compared with healthy controls (median 22 630, IQR [16 945; 43 200] in HC, 9510 IQR [3866; 14 215] in patients without immunosuppressive treatment (p<0.001), 7780 IQR [2203; 15 645] in patients receiving a single immunomodulatory drug (p<0.0001) and 14 320 IQR [2415; 35 400] in patients receiving combination therapy (p=0.081)).ConclusionsPatients with SARD displayed lower antibody development after booster vaccination, even if antibody levels after two immunisations were comparable to healthy controls. Our data may be limited due to sample size, but it provides pointers for a more individualised, antibody-titre-oriented approach and earlier booster vaccination in patients with SARD.

Objective To determine whether the presence of conventional radiography (CR)-detected osteophytes is associated with focal thickening of the hyaline cartilage by ultrasound (US) in the same area of the metacarpal head in a within-person, between-joint cross-sectional comparison in patients with hand osteoarthritis (HOA). Design 64 patients with HOA (classified using the 1990 ACR classification criteria) were screened. Participants were eligible for inclusion if they displayed osteophytes in at least one of their metacarpophalangeal (MCP) joints, no osteophytes in the contralateral corresponding MCP joint and no joint space narrowing (JSN) in either MCP joint by CR. In these patients, cartilage thickness was measured by US in 2 subregions of both metacarpal heads (i.e., the central force-bearing and the proximal peripheral area). Location-specific association between osteophytes and cartilage thickness was evaluated. Results 14/64 (21.9%) patients and 23 pairs of MCP joints were included in the analysis. Metacarpal heads with osteophytes had significantly thicker hyaline cartilage than contralateral ones without osteophytes in the proximal peripheral area of the hyaline cartilage [0.78 mm and 0.66 mm, respectively ( p  < 0.01)]. On the other hand, no difference in terms of cartilage thickness was found between the metacarpal heads with osteophytes and the contralateral ones without osteophytes in the central force-bearing area of the hyaline cartilage [0.65 mm and 0.66 mm, respectively ( p  = 0.53)]. Conclusions MCP joints with early radiographic HOA display thicker hyaline cartilage than contralateral MCP joints without radiographic signs of HOA, specifically in the proximal peripheral subregion of the metacarpal head. Key messages • Metacarpal heads with early radiographic osteoarthritis display thicker hyaline cartilage than contralateral ones without signs of osteoarthritis. • This ultrasonographic sign should be kept in mind to avoid misinterpretation of cartilage pathologies. • We provide pictorial ultrasonographic evidence of this “giant cartilage” sign.

Background Our aim was to investigate the role of nicotinic acetylcholine receptors (nAChRs) in in-vitro osteoclastogenesis and in in-vivo bone homeostasis. Methods The presence of nAChR subunits as well as the in-vitro effects of nAChR agonists were investigated by ex vivo osteoclastogenesis assays, real-time polymerase chain reaction, Western blot and flow cytometry in murine bone marrow-derived macrophages differentiated in the presence of recombinant receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The bone phenotype of mice lacking various nAChR subunits was investigated by peripheral quantitative computed tomography and histomorphometric analysis. Oscillations in the intracellular calcium concentration were detected by measuring the Fura-2 fluorescence intensity. Results We could demonstrate the presence of several nAChR subunits in bone marrow-derived macrophages stimulated with RANKL and M-CSF, and showed that they are capable of producing acetylcholine. nAChR ligands reduced the number of osteoclasts as well as the number of tartrate-resistant acidic phosphatase-positive mononuclear cells in a dose-dependent manner. In vitro RANKL-mediated osteoclastogenesis was reduced in mice lacking α7 homomeric nAChR or β2-containing heteromeric nAChRs, while bone histomorphometry revealed increased bone volume as well as impaired osteoclastogenesis in male mice lacking the α7 nAChR. nAChR ligands inhibited RANKL-induced calcium oscillation, a well-established phenomenon of osteoclastogenesis. This inhibitory effect on Ca 2+ oscillation subsequently led to the inhibition of RANKL-induced NFATc1 and c-fos expression after long-term treatment with nicotine. Conclusions We have shown that the activity of nAChRs conveys a marked effect on osteoclastogenesis in mice. Agonists of these receptors inhibited calcium oscillations in osteoclasts and blocked the RANKL-induced activation of c-fos and NFATc1. RANKL-mediated in-vitro osteoclastogenesis was reduced in α7 knockout mice, which was paralleled by increased tibial bone volume in male mice in vivo.

Objective Local bone destruction in rheumatic diseases, which often leads to disability and severely reduced quality of life, is almost exclusively mediated by osteoclasts. Therefore, it is important to understand pathways regulating the generation of osteoclasts. Here, we analysed the impact of the Phosphoinositide-3-Kinase (PI3K)/Phosphatase and tensin homolog (PTEN) axis on osteoclast generation and bone biology under basal and inflammatory conditions. Methods We analysed osteoclastogenesis of wildtype (wt) and PTEN−/− cells in vitro and in vivo, pit resorption and qPCR of osteoclasts in vitro. Mice with a myeloid cell-specific deletion of PTEN and wt littermate mice were investigated by bone histomorphometry and clinical and histological assessment in the human tumour necrosis factor (TNF)-transgenic (hTNFtg) arthritis model. Results We show that myeloid-specific PTEN−/− mice display increased osteoclastogenesis in vitro and in vivo compared to wt mice. Loss of PTEN did not affect the generation or survival of osteoclast precursor cells. However, PTEN deficiency greatly enhanced receptor activator of nuclear factor κ-B ligand (RANKL)-induced expression of the master transcription factor of osteoclastogenesis, nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), resulting in markedly increased terminal differentiation of osteoclasts in vitro. We also observed increased osteoclastogenesis under inflammatory conditions in the hTNFtg mouse model of arthritis, where hTNFtg/myeloid-specific PTEN−/− mice displayed enhanced local bone destruction as well as osteoclast formation in the inflamed joints. The extent of synovial inflammation, however, as well as recruitment of osteoclast precursor cells was not different between wt and myeloid-specific PTEN−/− mice. Conclusions These data demonstrate that loss of PTEN and, therefore, sustained PI3-Kinase signalling in myeloid cells especially, elevates the osteoclastogenic potential of myeloid cells, leading to enhanced inflammatory local bone destruction. Therefore, although our study allows no direct translational conclusion since we used a conditional knockout approach, the therapeutic targeting of the PI3-Kinase pathway may be of benefit in preventing structural joint damage.

ObjectiveTo systematically assess the evidence on the use of ultrasonography (US) for the detection of vascular inflammation in Takayasu arteritis (TAK), with a focus on evaluating existing scoring systems and identifying elementary sonographic lesions for diagnosis, disease monitoring and outcome prediction.MethodsA systematic literature review (SLR) was conducted using PubMed, EMBASE, the Cochrane Library and Epistemonikos from their inception until 15 March 2024. Only original research articles evaluating the diagnostic accuracy, outcome prediction or monitoring ability of US in TAK, with a minimum sample size of 15 patients, were included. Data extraction was performed independently by two reviewers. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool for diagnostic studies and the Quality In Prognosis Studies tool for prognostic studies.Results21 studies met the inclusion criteria. Three of them proposed a US scoring system for TAK, while the remainder focused on reporting elementary lesions. The common findings included increased intima-media thickness (IMT), stenosis, occlusion, aneurysm and increased contrast enhancement. All studies evaluated the common carotid arteries, with less frequent assessment of other vascular territories such as the subclavian and common femoral arteries and the abdominal aorta. Although increased IMT and contrast enhancement of the arterial wall correlated with clinical measures of disease activity, heterogeneity of lesion definitions and measurement thresholds, along with small sample sizes and moderate-to-high risk of bias, limits the generalisability of the findings.ConclusionsThis SLR highlights the current lack of a fully validated US scoring system for TAK and underscores the need for standardised definitions of elementary sonographic lesions.