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Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

Objective To assess the association of worsening of magnetic resonance imaging (MRI) semi-quantitative (SQ) tissue features with concurrent change in quantitative (Q) cartilage thickness measurements over 24 months within the Foundation for the National Institutes of Health (FNIH) Biomarker Consortium study. Methods In all, 599 participants were included. SQ assessment included cartilage damage, meniscal extrusion and damage, osteophytes, bone marrow lesions (BMLs), and effusion- and Hoffa-synovitis. Change in medial compartment Q cartilage thickness was stratified by concurrent ipsicompartmental SQ changes. Between-group comparisons were performed using analysis of covariance (ANCOVA) with adjustment for age, sex, and body mass index (BMI). Results were presented as adjusted mean difference. Results Knees with any increase in SQ cartilage scores in the medial compartment ( n = 268) showed more Q cartilage loss compared to knees that remained stable (mean adjusted difference [MAD] = -0.16 mm, 95% confidence interval [CI]: [-0.19, -0.13] mm). Knees with any increase in meniscal extrusion in the medial compartment (n = 98) showed more Q cartilage loss than knees without (MAD = -0.18 mm, 95% CI: [-0.22, -0.14] mm. Comparable findings were seen for meniscal damage worsening. Regarding BMLs, an increase by one subregion resulted in a MAD of Q cartilage loss of -0.10 mm, 95% CI: [-0.14, -0.06] mm, while this effect almost tripled for change in two or more subregions. Increase in either effusion- and/or Hoffa-synovitis by one grade resulted in a MAD of -0.07 mm, 95% CI: [-0.10, -0.03] mm. Conclusion Worsening of SQ cartilage damage, meniscal extrusion and damage, number of subregions affected by BML, maximum size of BMLs and worsening of effusion- and/or Hoffa synovitis is associated with increased Q cartilage loss.

Quantitative measures of cartilage morphology (“cartilage morphometry”) extracted from high resolution 3D magnetic resonance imaging (MRI) sequences have been shown to be sensitive to osteoarthritis (OA)-related change and also to treatment interventions. Cartilage morphometry is therefore nowadays widely used as outcome measure for observational studies and randomized interventional clinical trials. The objective of this narrative review is to summarize the current status of cartilage morphometry in OA research, to provide insights into aspects relevant for the design of future studies and clinical trials, and to give an outlook on future developments. It covers the aspects related to the acquisition of MRIs suitable for cartilage morphometry, the analysis techniques needed for deriving quantitative measures from the MRIs, the quality assurance required for providing reliable cartilage measures, and the appropriate participant recruitment criteria for the enrichment of study cohorts with knees likely to show structural progression. Finally, it provides an overview over recent clinical trials that relied on cartilage morphometry as a structural outcome measure for evaluating the efficacy of disease-modifying OA drugs (DMOAD).

ObjectiveTo compare the evaluation metrics for deep learning methods in the imbalanced imaging data in osteoarthritis (OA) studies.MethodWe first divided MOAKS (MRI Osteoarthritis Knee Score) grades into the presence (MOAKS > 0) and absence (MOAKS = 0) categories. Second, a deep-learning model was trained to the sagittal intermediate-weighted (IW) fat-suppressed (FS) knee MRI images with MOAKS readings from the Osteoarthritis Initiative (OAI) study to predict the presence of bone marrow lesions (BMLs). After the deep learning models were trained, we obtained probabilities of the presence of BMLs from MRI images at the sub-region (15 sub-regions), compartment, and whole-knee levels. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) of the deep learning model in the testing data with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model’s performance.ResultsWe have demonstrated that the commonly used ROC curve is not sufficiently informative when evaluating the performance of deep learning models in the imbalanced data in OA studies.ConclusionThe class ratios coupled with results of ROC, PR, and Matthews correlation coefficient (MCC) should be reported in OA studies.

Background We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence. Methods Using the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) 2/year, -26.70 – -5.41) but not thigh muscles’ composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15–2.75 and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19–3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use. Conclusions Our exploratory analyses suggest that levothyroxine use is associated with loss of quadriceps muscle mass, which partially mediates increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier; and therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes of thigh muscles.

Objectives To evaluate whether neural networks can distinguish between seropositive RA, seronegative RA, and PsA based on inflammatory patterns from hand MRIs and to test how psoriasis patients with subclinical inflammation fit into such patterns. Methods ResNet neural networks were utilized to compare seropositive RA vs PsA, seronegative RA vs PsA, and seropositive vs seronegative RA with respect to hand MRI data. Results from T1 coronal, T2 coronal, T1 coronal and axial fat-suppressed contrast-enhanced (CE), and T2 fat-suppressed axial sequences were used. The performance of such trained networks was analysed by the area under the receiver operating characteristics curve (AUROC) with and without presentation of demographic and clinical parameters. Additionally, the trained networks were applied to psoriasis patients without clinical arthritis. Results MRI scans from 649 patients (135 seronegative RA, 190 seropositive RA, 177 PsA, 147 psoriasis) were fed into ResNet neural networks. The AUROC was 75% for seropositive RA vs PsA, 74% for seronegative RA vs PsA, and 67% for seropositive vs seronegative RA. All MRI sequences were relevant for classification, however, when deleting contrast agent–based sequences the loss of performance was only marginal. The addition of demographic and clinical data to the networks did not provide significant improvements for classification. Psoriasis patients were mostly assigned to PsA by the neural networks, suggesting that a PsA-like MRI pattern may be present early in the course of psoriatic disease. Conclusion Neural networks can be successfully trained to distinguish MRI inflammation related to seropositive RA, seronegative RA, and PsA.

Skeletal muscle mass is subjected to constant changes and is considered a good predictor for outcome in various diseases. Bioelectrical-impedance analysis (BIA) and magnetic resonance imaging (MRI) are approved methodologies for its assessment. However, muscle mass estimations by BIA may be influenced by excess intramuscular lipids and adipose tissue in obesity. The objective of this study was to evaluate the feasibility of quantitative assessment of skeletal muscle mass by MRI as compared with BIA.Subjects from a population-based cohort underwent BIA (50 kHz, 0.8 mA) and whole-body MRI including chemical-shift encoded MRI (six echo times). Abdominal muscle mass by MRI was quantified as total and fat-free cross-sectional area by a standardized manual segmentation-algorithm and normalized to subjects' body heightAmong 335 included subjects (56.3 ± 9.1 years, 56.1% male), 95 (28.4%) were obese (BMI ≥ 30 kg/mMRI-based assessment of muscle mass is feasible in population-based imaging and strongly correlated with BIA. However, the observed weaker correlation in obese subjects may explain the known limitation of BIA in obesity and promote MRI-based assessments. Thus, skeletal muscle mass parameters by MRI may serve as practical imaging biomarkers independent of subjects' body weight.

Aim was to describe three definitions for an MRI-defined cartilage-meniscus phenotype and to report phenotypic progression in Kellgren-Lawrence (KL) 2 and 3 knees over 48 months.The study sample was a nested case-control study with knees showing either 1) radiographic and pain progression ("composite" case), 2) radiographic progression only, 3) pain progression only, and 4) no progression. MRI was performed on 3T systems. MRIs were read according to the MOAKS system. Knees were classified as having the cartilage-meniscus phenotype according to three modified ROAMES (Rapid OsteoArthritis MRI Eligibility Score) definitions (D): 1) ​≤ ​2.2 (10-75% of the region of cartilage surface area with 10-75% affected by full thickness loss), i.e. 'D1' 2) ≤ 2.1 (10-75% of the region of cartilage surface area with10% affected by full thickness loss), i.e. 'D2' and 3) ≤ 2.0 (10-75% of the region of cartilage surface area without full thickness loss), i.e. 'D3'. The odds of being a composite case for those with vs. without each definition was determined using logistic regression.485 knees were included. For KL2 knees 191 (64%) knees fulfilled D1 criteria, 183 (62%) D2 and 167 (56%) D3. For KL3 these numbers were 164 (87%), 103 (55%) and 77 (41%). Odds for being a composite case for KL2 knees were 2.52 (95% CI 1.40,4.54) for D1, 1.93 (95% CI 1.11,3.35) for D2 and 1.92 (95% CI 1.13,3.28) for D3. For KL3 knees odds were 0.32 (95% CI 0.13,0.78) for D1, 0.56 (95% CI 0.31,1.01) for D2 and 0.49 (95% CI 0.26,0.91) for D3.Increased odds for progression are seen for KL2 knees for all definitions, while this was not observed for KL3 knees. KL3 knees exceeding the maximum damage thresholds and not fulfilling the phenotypic definitions are still likely to experience further progression.

Objective. The aim of this study was to determine the reliability of an MRI-based score that evaluates forefoot bursae (FFBs) in patients with RA.Methods. Items for inclusion, grading criteria and MRI sequences were determined iteratively. The score was evaluated in 30 patients with established RA. Reader agreement was evaluated using the percentage of exact/close agreement, Bland–Altman plots, kappa and intraclass correlation coefficient analyses.Results. The FFB score assesses nine forefoot regions and contains four items: presence, shape, enhancement and magnetic resonance characteristics. The FFB score showed moderate to good intra- and interreader agreement (κ range = 0.5–0.9 and 0.47–0.87, respectively).Conclusion. The FFB score is adequately reliable in the evaluation of bursa-like lesions of the forefoot in patients with RA.

Painful knee osteoarthritis (KOA) has been associated with joint inflammation. There is, however, little literature correlating signs of localized inflammation with contrast-enhanced (CE) magnetic resonance imaging (MRI) of synovium. This study examined the relationship between clinical and functional markers of localized knee inflammation and CE MRI-based synovial scores.Patients with symptomatic KOA were enrolled into the randomized, double-blind, Vitamin D Evaluation in Osteoarthritis (VIDEO) trial. In this cross-sectional substudy, associations between validated MRI-based semiquantitative synovial scores of the knee and the following markers of inflammation were investigated: self-reported pain and stiffness, effusion, warmth, joint line tenderness, erythrocyte sedimentation rate, radiographic severity, and functional ability tests.A total of 107 patients satisfied the inclusion criteria of complete data and were included in the analysis. Significant associations were found between the number of regions affected by synovitis and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, effusion, and joint line tenderness. Each additional region affected by synovitis was associated with an increase in WOMAC pain (1.82 [95% confidence interval (95% CI) 0.05, 3.58], P = 0.04), and the association with extent of medial synovitis was particularly strong (3.21 [95% CI 0.43, 5.99], P = 0.02). Extent of synovitis was positively associated with effusion (odds ratio 1.69 [95% CI 1.37, 2.08], P 0.01) and negatively associated with joint line tenderness (relative risk 0.87 [95% CI 0.84, 0.90], P 0.01).There is a strong positive association between synovitis and self-reported patient pain and clinically detectable effusion. Nonoperative treatments directed at management of inflammation and future trials targeting the synovial tissue for treating KOA should consider these 2 factors as potential inclusion criteria.

High knee extensor strength may be important to protect against the development of knee osteoarthritis (OA) in populations at elevated risk, such as individuals with meniscal pathology. We investigated the extent to which high knee extensor muscle strength was associated with a decreased risk of developing radiographic or symptomatic knee OA in individuals with medial meniscal pathology.We studied knees that at the baseline visit of the Multicenter Osteoarthritis Study had medial meniscal pathology but did not have radiographic knee OA (373 knees in 373 participants) or symptomatic knee OA (combination of radiographic knee OA and frequent knee symptoms; 531 knees in 531 participants). Isokinetic knee extensor strength was measured at baseline, and participants were followed for development of incident radiographic knee OA or incident symptomatic knee OA at 84 months. Separate binomial regression analyses with robust SEs adjusted for age, history of knee surgery, physical activity level, and clinic site were conducted for men and women.High knee extensor strength (normalized by allometric scaling) was associated with a reduced risk of radiographic knee OA in women (relative risk [RR] 0.52, 95% confidence interval [95% CI] 0.29-0.94) but not in men (RR 0.56, 95% CI 0.27-1.16). High knee extensor strength did not protect against the development of symptomatic knee OA, either in women or men.The results only partly confirm the hypothesis that high knee extensor muscle strength protects against later development of knee OA in individuals with medial meniscal pathology.

To identify patterns of coexisting lesions seen on magnetic resonance imaging (MRI) in knees that are free of radiographic osteoarthritis (OA) and to examine the relationship of these MRI-detected lesions to incident OA.Study subjects were individuals enrolled in the Multicenter Osteoarthritis Study, a prospective cohort study. In each subject, 1 knee in which radiographic OA was absent in both the tibiofemoral and patellofemoral joints at baseline was selected for study, with followup for 84 months. We used a novel approach, latent class analysis, to group the constellation of MRI lesions in each joint, i.e., cartilage damage, bone marrow lesion, meniscal tear, meniscal extrusion, synovitis, and effusion, into a manageable number of subgroups. The association of these subgroups with incident radiographic OA in the same joint was assessed using logistic regression.Among 885 eligible knees (203 with incident disease in the tibiofemoral joint, 64 with incident disease in the patellofemoral joint), 4 latent subgroups in the tibiofemoral joint were identified (described briefly as minimal lesions, mild lesions, moderate lesions [but limited meniscal lesions], and severe lesions). The odds ratios of incident tibiofemoral joint OA in the latter 3 subgroups (compared to the knees with minimal lesions as the referent) were 5.6, 1.8, and 5.0, respectively. A similar set of 4 subgroups in the patellofemoral joint was identified, except that the fourth subgroup had limited meniscal lesions. The odds ratios of incident disease in the patellofemoral joint were 3.8, 5.1, and 13.7 in the subgroups with mild lesions, moderate lesions, and severe lesions, respectively.Different patterns of coexisting MRI lesions, which have different implications with regard to risk of knee OA, were identified. Meniscal damage seemed to play a different role in the development of incident disease in tibiofemoral versus patellofemoral joints.

Objective: To test the hypothesis that cartilage displays significant longitudinal thickening in the external subregions of the central medial (ecMF) and lateral (ecLF) femur in knees with early radiographic osteoarthritis (ROA) compared with contralateral knees without ROA, and to explore differences in change in other subregions and in radiographic joint space width (JSW). Methods: 50 participants (50% women; age 61.1±9.7y; BMI 27.7±4.7kg/m2 ) were identified from the Osteoarthritis Initiative cohort with definite femorotibial osteophytes but no JSN in one knee (early ROA), and no osteophytes or JSN in the contralateral knee (non-ROA). A longitudinal within-person, between-knee comparison was performed using measures of subregional cartilage thickness based on analyses of sagittal DESSwe MR images obtained at baseline and 1-year. Medial JSW was evaluated from fixed flexion radiographs. Results: The change between baseline and 1-year was -6±94µm in ecMF and +18±91µm in ecLF in early ROA (p=0.78) vs. -1±68µm and +4±76µm in non-ROA knees (p=0.38). The variability of cartilage thickness change tended to be greater in early ROA than in non-ROA knees. Greater cartilage thickness loss in the lateral tibia and a greater reduction in minimum medial JSW was observed in early ROA vs. non-ROA knees. Conclusion: There was no direct evidence of longitudinal cartilage thickening in external subregions of the central femur in knees with early ROA compared with contralateral non-ROA knees. The observed greater variability in longitudinal thickness change in early ROA knees (but not in non-ROA knees) might be due to cartilage thickening and thinning occurring simultaneously in these knees.

A speaker support system, adapted to prevent destructive resonance between a speaker and a speaker cabinet, comprising a vibration damper, a vibration transferer, and a connector. The speaker support prevents primary-mode resonance from building up to damaging levels in a speaker cabinet. The vibration damper damps sound vibrations that are passing from a speaker into a speaker cabinet. The vibration damper is tuned to not resonate at any resonant frequency of the speaker cabinet. The vibration transferer transfers sound vibrations from the vibration damper to a vibration sink, which is preferably a portion of the speaker cabinet that is remote from the vibration damper. Preferably, the vibration transferer comprises a metal rod. The connector fixedly connects the vibration transferer to the vibration sink. The vibration transferer is tuned to not resonate at any resonant frequency of the speaker cabinet.

A rebuildable low frequency loudspeaker driver has a replaceable diaphragm assembly. In a first embodiment, the peripheral edge of a loudspeaker driver diaphragm comprises a flexible surround and is releaseably supported within a matching basket having a peripheral mounting flange clamping surface to which a rigid ring-shaped clamping member or gasket is releaseably attached. A parts kit includes a replacement cone assembly with a frustoconical cone having an attached annular surround at the large cone end and a flexible spider attached near the small cone end, adjacent the attachment point for the cylindrical voice coil former. The spider includes a rigid ring mounted at the spider peripheral edge and dimensioned to be removably fastened to the driver basket. The driver basket includes a spider plateau region including a valley with sidewalls adapted to receive and center the spider rigid ring. The rebuilding method includes the steps of removing the expended cone assembly, cleaning the magnetic gap (if necessary) aligning the replacement cone assembly voice coil former over the motor pole piece, fastening the spider ring, removing the spacer paper alignment tool, and gluing a new dust cover over the center of the cone.

Parmi les eleves du “Staatliches Lehrerseminar Biel” le nombre de fumeurs etait plus bas en 1984 qu'en 1977. Tel fut le resultat de deux enquetes par questionnaire consecutives. Etant donne que 80% des eleves sont des filles, cette observation represente la premiere documentation d'une diminution du taux des fumeurs parmi des jeunes filles en Suisse.