Primary anterior cruciate ligament repair-morphological and quantitative assessment by 7-T MRI and clinical outcome after 1.5 years.

OBJECTIVES: The purpose of this study was to assess morphological and quantitative changes of the anterior cruciate ligament (ACL) and cartilage after ACL repair. METHODS: 7T MRI of the knee was acquired in 31 patients 1.5 years after ACL repair and in 13 controls. Proton density-weighted images with fat saturation (PD-fs) were acquired to assess ACL width, signal intensity, elongation, and fraying. T2/T2* mapping was performed for assessment of ACL and cartilage. Segmentation of the ACL, femoral, and tibial cartilage was carried out at 12 ROIs. The outcome evaluation consisted of the Lysholm Knee Score and International Knee Documentation Committee (IKDC) subjective score and clinical examination. RESULTS: ACL showed a normal signal intensity in 96.8% and an increased width in 76.5% after repair. Fraying occurred in 22.6% without having an impact on the clinical outcome (Lysholm score: 90.39 ± 9.75, p = 0.76 compared to controls). T2 analysis of the ACL revealed no difference between patients and controls (p = 0.74). Compared to controls, assessment of the femoral and tibial cartilage showed a significant increase of T2* times in all ROIs, except at the posterolateral femur. Patients presented a good outcome in clinical examination with a Lysholm score of 87.19 ± 14.89 and IKDC of 80.23 ± 16.84. CONCLUSION: T2 mapping results suggest that the tissue composition of the ACL after repair is similar to that of a native ACL after surgery, whereas the ACL exhibits an increased width. Fraying of the ACL can occur without having any impact on functional outcomes. T2* analysis revealed early degradation at the cartilage. CLINICAL RELEVANCE STATEMENT: MRI represents a noninvasive diagnostic tool for the morphological and compositional assessment of the anterior cruciate ligament after repair, whereas knowledge about post-surgical alterations is crucial for adequate imaging interpretation. KEY POINTS: • There has been renewed interest in repairing the anterior cruciate ligament with a proximally torn ligament. • T2 times of the anterior cruciate ligament do not differ between anterior cruciate ligament repair patients and controls. • T2 mapping may serve as a surrogate for the evaluation of the anterior cruciate ligament after repair.

Pre-assessment of patients with suspected axial spondyloarthritis combining student-led clinics and telemedicine: a qualitative study.

OBJECTIVE: Patients referred to rheumatologists are currently facing months of inefficient waiting time due to the increasing demand and rising workforce shortage. We piloted a pre-assessment of patients with suspected axial spondyloarthritis (axSpA) combining student-led clinics and telemedicine (symptom assessment, symptom monitoring and at-home capillary self-sampling) to improve access to rheumatology care. The aim of this study was to explore (1) current challenges accessing axSpA care and (2) patients' first-hand experiences. METHODS: Embedded within a clinical trial, this study was based on qualitative interviews with patients with suspected axSpA (n = 20). Data was analysed via qualitative content analysis. RESULTS: Student-led clinics were perceived as high-quality care, comparable to conventional rheumatologist-led visits. Patients expressed that their interactions with the students instilled a sense of trust. History-taking and examinations were perceived as comprehensive and meticulous. Telehealth tools were seen as empowering, offering immediate and continuous access to symptom assessment at home. Patients reported a lack of specificity of the electronic questionnaires, impeding accurate responses. Patients requested a comments area to supplement questionnaire responses. Some patients reported receiving help to complete the blood collection. CONCLUSION: Patients' access to rheumatology care is becoming increasingly burdensome. Pre-assessment including student-led clinics and telemedicine was highly accepted by patients. Patient interviews provided valuable in-depth feedback to improve the piloted patient pathway.

Contrast-Enhanced Multispectral Optoacoustic Tomography for Functional Assessment of the Gastrointestinal Tract.

Real-time imaging and functional assessment of the intestinal tract and its transit pose a significant challenge to conventional clinical diagnostic methods. Multispectral optoacoustic tomography (MSOT), a molecular-sensitive imaging technology, offers the potential to visualize endogenous and exogenous chromophores in deep tissue. Herein, a novel approach using the orally administered clinical-approved fluorescent dye indocyanine green (ICG) for bedside, non-ionizing evaluation of gastrointestinal passage is presented. The authors are able to show the detectability and stability of ICG in phantom experiments. Furthermore, ten healthy subjects underwent MSOT imaging at multiple time points over eight hours after ingestion of a standardized meal with and without ICG. ICG signals can be visualized and quantified in different intestinal segments, while its excretion is confirmed by fluorescent imaging of stool samples. These findings indicate that contrast-enhanced MSOT (CE-MSOT) provides a translatable real-time imaging approach for functional assessment of the gastrointestinal tract.

Assessment of myocardial fibrosis in patients with systemic sclerosis using [68Ga]Ga-FAPI-04-PET-CT.

PURPOSE: Myocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization of fibroblast activation as early readout of MF has not been feasible to date. Here, we characterize 68Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([68Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF. METHODS: In this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [68Ga]Ga-FAPI-04-PET-CT and cardiac MRI (cMRI) and clinical and serologic investigations just before baseline and during follow-up between January 2020 and December 2020. Myocardial biopsy was performed as clinically indicated. RESULTS: [68Ga]Ga-FAPI-04 tracer uptake was increased in SSc-related MF with higher uptake in SSc patients with arrhythmias, elevated serum-NT-pro-BNP, and increased late gadolinium enhancement (LGE) in cMRI. Histologically, myocardial biopsies from cMRI- and [68Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP+ fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [68Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [68Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [68Ga]Ga-FAPI-04 uptake associated with changes in the activity of SSc-related MF, while cMRI parameters remained stable after regression of molecular activity and rather indicated tissue damage. CONCLUSIONS: We present first in-human evidence that [68Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.

Gender equity in academic rheumatology, current status and potential for improvement: a cross-sectional study to inform an EULAR task force.

OBJECTIVES: Evidence on the current status of gender equity in academic rheumatology in Europe and potential for its improvement is limited. The EULAR convened a task force to obtain empirical evidence on the potential unmet need for support of female rheumatologists, health professionals and non-clinical scientists in academic rheumatology. METHODS: This cross-sectional study comprised three web-based surveys conducted in 2020 among: (1) EULAR scientific member society leaders, (2) EULAR and Emerging EULAR Network (EMEUNET) members and (3) EULAR Council members. Statistics were descriptive with significance testing for male/female responses assessed by χ2 test and t-test. RESULTS: Data from EULAR scientific member societies in 13 countries indicated that there were disproportionately fewer women in academic rheumatology than in clinical rheumatology, and they tended to be under-represented in senior academic roles. From 324 responses of EULAR and EMEUNET members (24 countries), we detected no gender differences in leadership aspirations, self-efficacy in career advancement and work-life integration as well as the share of time spent on research, but there were gender differences in working hours and the levels of perceived gender discrimination and sexual harassment. There were gender differences in the ranking of 7 of 26 factors impacting career advancement and of 8 of 24 potential interventions to aid career advancement. CONCLUSIONS: There are gender differences in career advancement in academic rheumatology. The study informs a EULAR task force developing a framework of potential interventions to accelerate gender-equitable career advancement in academic rheumatology.

Review and Analysis of German Mobile Apps for Inflammatory Bowel Disease Management Using the Mobile Application Rating Scale: Systematic Search in App Stores and Content Analysis.

BACKGROUND: Patients suffering from inflammatory bowel disease (IBD) frequently need long-term medical treatment. Mobile apps promise to complement and improve IBD management, but so far there has been no scientific analysis of their quality. OBJECTIVE: This study evaluated the quality of German mobile apps targeting IBD patients and physicians treating IBD patients using the Mobile Application Rating Scale (MARS). METHODS: The German Apple App Store and Google Play Store were systematically searched to identify German IBD mobile apps for patient and physician use. MARS was used by 6 physicians (3 using Android smartphones and 3 using iPhones) to independently assess app quality. Apps were randomly assigned so that the 4 apps with the most downloads were rated by all raters and the remaining apps were rated by 1 Android and 1 iOS user. RESULTS: In total, we identified 1764 apps in the Apple App Store and Google Play Store. After removing apps that were not related to IBD (n=1386) or not available in German (n=317), 61 apps remained. After removing duplicates (n=3) and apps for congresses (n=7), journals (n=4), and clinical studies (n=6), as well as excluding apps that were available in only 1 of the 2 app stores (n=20) and apps that could only be used with an additional device (n=7), we included a total of 14 apps. The app "CED Dokumentation und Tipps" had the highest overall median MARS score at 4.11/5. On the whole, the median MARS scores of the 14 apps ranged between 2.38/5 and 4.11/5. As there was no significant difference between iPhone and Android raters, we used the Wilcoxon comparison test to calculate P values. CONCLUSIONS: The MARS ratings showed that the quality of German IBD apps varied. We also discovered a discrepancy between app store ratings and MARS ratings, highlighting the difficulty of assessing perceived app quality. Despite promising results from international studies, there is little evidence for the clinical benefits of German IBD apps. Clinical studies and patient inclusion in the app development process are needed to effectively implement mobile apps in routine care.

Patient's Perception of Digital Symptom Assessment Technologies in Rheumatology: Results From a Multicentre Study.

Introduction: An increasing number of digital tools, including dedicated diagnostic decision support systems (DDSS) exist to better assess new symptoms and understand when and where to seek medical care. The aim of this study was to evaluate patient's previous online assessment experiences and to compare the acceptability, usability, usefulness and potential impact of artificial intelligence (AI)-based symptom checker (Ada) and an online questionnaire-based self-referral tool (Rheport). Materials and Methods: Patients newly presenting to three German secondary rheumatology outpatient clinics were randomly assigned in a 1:1 ratio to complete consecutively Ada or Rheport in a prospective non-blinded multicentre controlled crossover randomized trial. DDSS completion time was recorded by local study personnel and perceptions on DDSS and previous online assessment were collected through a self-completed study questionnaire, including usability measured with the validated System Usability Scale (SUS). Results: 600 patients (median age 52 years, 418 women) were included. 277/600 (46.2%) of patients used an online search engine prior to the appointment. The median time patients spent assessing symptoms was 180, 7, and 8 min, respectively using online using search engines, Ada and Rheport. 111/275 (40.4%), 266/600 (44.3%) and 395/600 (65.8%) of patients rated the respective symptom assessment as very helpful or helpful, using online search engines, Ada and Rheport, respectively. Usability of both diagnostic decision support systems (DDSS) was "good" with a significantly higher mean SUS score (SD) of Rheport 77.1/100 (16.0) compared to Ada 74.4/100 (16.8), (p < 0.0001). In male patients, usability of Rheport was rated higher than Ada (p = 0.02) and the usability rating of older (52 years ≥) patients of both DDSS was lower than in younger participants (p = 0.005). Both effects were independent of each other. 440/600 (73.3%) and 475/600 (79.2%) of the patients would recommend Ada and Rheport to friends and other patients, respectively. Conclusion: In summary, patients increasingly assess their symptoms independently online, however only a minority used dedicated symptom assessment websites or DDSS. DDSS, such as Ada an Rheport are easy to use, well accepted among patients with musculoskeletal complaints and could replace online search engines for patient symptom assessment, potentially saving time and increasing helpfulness.

Quality of a Supporting Mobile App for Rheumatic Patients: Patient-Based Assessment Using the User Version of the Mobile Application Scale (uMARS).

Introduction: Mobile applications promise to improve current health care. However, current mobile app quality ratings are mostly physician-based. The aim of this study was (1) to assess the quality of the self-management app Rheuma Auszeit using the validated uMARS (User Version of the Mobile App Rating Scale) app quality assessment tool and (2) to evaluate the association between uMARS scores and patients' characteristics. Materials and Methods: Consecutive patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis were seen at the rheumatology clinic at university hospital Erlangen, Germany. They were asked to test Rheuma Auszeit, evaluate its quality using uMARS and complete a paper-based survey evaluating the individual preferences, attitudes and ehealth literacy. The association between uMARS scores and patients' characteristics was further explored. Results: Between December 2018 and January 2019, a total of 126 patients evaluated Rheuma Auszeit using uMARS and filled out the paper-based survey. The median uMARS score was 3.9, IQR 0.7. Functionality was the domain with the highest rating (median 4.8, IQR 0.8), followed by aesthetics (median 4.0, IQR 0.7), information (median 3.5, IQR 0.8), and engagement (median 3.2, IQR 1.0). Subjective quality was average (median 3.0, IQR 1.0). The lowest scoring individual item was customization with a median of 2.5/5. Lower functionality scores were reported among older female rheumatic patients (P < 0.004). Older male rheumatic patients reported a higher subjective quality score (P < 0.024). Perceived disease activity and disease duration did not significantly correlate with any uMARS subdomain scores. eHealth literacy significantly correlated with functionality uMARS subdomain ratings (Rho = 0.18; P < 0.042). Preferred time of app usage significantly correlated with engagement (Rho = 0.20; P < 0.024), functionality (Rho = 0.19; P < 0.029), total uMARS score (Rho = 0.21; P < 0.017) and subjective quality score (Rho = 0.21; P < 0.017). The vast majority of rheumatic patients would consider recommending Rheuma Auszeit to other patients (117/126; 92.9%). Conclusion: Rheuma Auszeit was well-accepted by German patients suffering from rheumatoid arthritis, psoriatic arthritis and ankylosing spondyloarthritis. Lacking customization could lead to low app compliance and should be improved. Lower functionality scores among older female rheumatic patients highlight the need for patient education. The study underlines the potential and feasibility of therapeutic complementary digital solutions in rheumatology.

Implementing an automated monitoring process in a digital, longitudinal observational cohort study.

BACKGROUND: Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research. METHODS: An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This "conflict catalog" was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried. RESULTS: Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40-64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59-69% were answered. The most common missing values were CRP, ESR, Schober's test, data on systemic glucocorticoid therapy, and presence of enthesitis. CONCLUSION: Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.

Key opinion leaders - a critical perspective.

Enormous progress has been made in the field of rheumatology in the past several decades, historically led by publicly funded academic innovators but in more recent times with much greater involvement of the pharmaceutical industry. This shift in resources has created a complex new model for reinvestment in the medical community in which the vast majority of private funds are redirected towards influencing the prescription behaviour of practitioners through 'key opinion leaders', with the main purpose of enhancing and perpetuating profit rather than innovation and critical thinking, and often at the expense of partnerships with scientists (that is, basic and translational researchers) and academic collaborations. This new episteme brings multiple opportunities to rethink approaches to sustaining long-term critical research in the field, ultimately maximizing the return on investment: scientific knowledge for the benefit of patients and society. Central to such strategies should be the rebalancing of academia-industry partnerships towards academic research and the involvement of 'innovation and knowledge leaders', rather than mostly key opinion leaders.

68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study.

BACKGROUND: Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis. To date, the progression of systemic sclerosis-associated ILD is judged by the accrual of lung damage on CT and pulmonary function tests. However, diagnostic tools to assess disease activity are not available. Here, we tested the hypothesis that quantification of fibroblast activation by PET-CT using a 68Ga-labelled selective inhibitor of prolyl endopeptidase FAP (68Ga-FAPI-04) would correlate with ILD activity and disease progression in patients with systemic sclerosis-associated ILD. METHODS: Between Sept 10, 2018, and April 8, 2020, 21 patients with systemic sclerosis-associated ILD confirmed by high-resolution CT (HRCT) within 12 months of inclusion and with onset of systemic sclerosis-associated ILD within 5 years or signs of progressive ILD and 21 controls without ILD were consecutively enrolled. All participants underwent 68Ga-FAPI-04 PET-CT imaging and standard-of-care procedures, including HRCT and pulmonary function tests at baseline. Patients with systemic sclerosis-associated ILD were followed for 6 months with HRCT and pulmonary function tests. We compared baseline 68Ga-FAPI-04 PET-CT uptake with standard diagnostic tools and predictors of ILD progression. The association of 68Ga-FAPI-04 uptake with changes in forced vital capacity was analysed using mixed-effects models. Follow-up 68Ga-FAPI-04 PET-CT scans were obtained in a subset of patients treated with nintedanib (follow-up between 6-10 months) to assess change over time. FINDINGS: 68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in patients with systemic sclerosis-associated ILD compared with controls, with a median standardised uptake value (SUV) mean over the whole lung of 0·80 (IQR 0·60-2·10) in the systemic sclerosis-ILD group and 0·50 (0·40-0·50) in the control group (p<0·0001) and a mean whole lung maximal SUV of 4·40 (range 3·05-5·20) in the systemic sclerosis-ILD group compared with 0·70 (0·65-0·70) in the control group (p<0·0001). Whole-lung FAPI metabolic active volume (wlFAPI-MAV) and whole-lung total lesion FAPI (wlTL-FAPI) were not measurable in control participants, because no 68Ga-FAPI-04 uptake above background level was observed. In the systemic sclerosis-ILD group the median wlFAPI-MAV was 254·00 cm3 (IQR 163·40-442·30), and the median wlTL-FAPI was 183·60 cm3 (98·04-960·70). 68Ga-FAPI-04 uptake was higher in patients with extensive disease, with previous ILD progression, or high EUSTAR activity scores than in those with with limited disease, previously stable ILD, or low EUSTAR activity scores. Increased 68Ga-FAPI-04 uptake at baseline was associated with progression of ILD independently of extent of involvement on HRCT scan and the forced vital capacity at baseline. In consecutive 68Ga-FAPI-04 PET-CTs, changes in 68Ga-FAPI-04 uptake was concordant with the observed response to the fibroblast-targeting antifibrotic drug nintedanib. INTERPRETATION: Our study presents the first in-human evidence that fibroblast activation correlates with fibrotic activity and disease progression in the lungs of patients with systemic sclerosis-associated ILD and that 68Ga-FAPI-04 PET-CT might improve risk assessment of systemic sclerosis-associated ILD. FUNDING: German Research Foundation, Erlangen Anschubs-und Nachwuchsfinanzierung, Interdisziplinäres Zentrum für Klinische Forschung Erlangen, Bundesministerium für Bildung und Forschung, Deutsche Stiftung Systemische Sklerose, Wilhelm-Sander-Foundation, Else-Kröner-Fresenius-Foundation, European Research Council, Ernst-Jung-Foundation, and Clinician Scientist Program Erlangen.

A new method for quantitative assessment of hand muscle volume and fat in magnetic resonance images.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by systemic inflammation and bone and muscle loss. Recent research showed that obesity facilitates inflammation, but it is unknown if obesity also increases the risk or severity of RA. Further research requires an accurate quantification of muscle volume and fat content. METHODS: The aim was to develop a reproducible (semi) automated method for hand muscle segmentation and quantification of hand muscle fat content and to reduce the time consuming efforts of manual segmentation. T1 weighted scans were used for muscle segmentation based on a random forest classifier. Optimal segmentation parameters were determined by cross validation with 30 manually segmented hand datasets (gold standard). An operator reviewed the automatically created segmentation and applied corrections if necessary. For fat quantification, the segmentation masks were automatically transferred to MRI Dixon sequences by rigid registration. In total 76 datasets from RA patients were analyzed. Accuracy was validated against the manual gold standard segmentations. RESULTS: Average analysis time per dataset was 10 min, more than 10 times faster compared to manual outlining. All 76 datasets could be analyzed and were accurate as judged by a clinical expert. 69 datasets needed minor manual segmentation corrections. Segmentation accuracy compared to the gold standard (Dice ratio 0.98 ± 0.04, average surface distance 0.04 ± 0.10 mm) and reanalysis precision were excellent. Intra- and inter-operator precision errors were below 0.3% (muscle) and 0.7% (fat). Average Hausdorff distances were higher (1.09 mm), but high values originated from a shift of the analysis VOI by one voxel in scan direction. CONCLUSIONS: We presented a novel semi-automated method for quantitative assessment of hand muscles with excellent accuracy and operator precision, which highly reduced a traditional manual segmentation effort. This method may greatly facilitate further MRI image based muscle research of the hands.

Toward Earlier Diagnosis Using Combined eHealth Tools in Rheumatology: The Joint Pain Assessment Scoring Tool (JPAST) Project.

Outcomes of patients with inflammatory rheumatic diseases have significantly improved over the last three decades, mainly due to therapeutic innovations, more timely treatment, and a recognition of the need to monitor response to treatment and to titrate treatments accordingly. Diagnostic delay remains a major challenge for all stakeholders. The combination of electronic health (eHealth) and serologic and genetic markers holds great promise to improve the current management of patients with inflammatory rheumatic diseases by speeding up access to appropriate care. The Joint Pain Assessment Scoring Tool (JPAST) project, funded by the European Union (EU) European Institute of Innovation and Technology (EIT) Health program, is a unique European project aiming to enable and accelerate personalized precision medicine for early treatment in rheumatology, ultimately also enabling prevention. The aim of the project is to facilitate these goals while at the same time, reducing cost for society and patients.

Comprehensive assessment of knee joint synovitis at 7 T MRI using contrast-enhanced and non-enhanced sequences.

BACKGROUND: Seven T ultra-high field MRI systems have recently been approved for clinical use by the U.S. and European regulatory agencies. These systems are now being used clinically and will likely be more widely available in the near future. One of the applications of 7 T systems is musculoskeletal disease and particularly peripheral arthritis imaging. Since the introduction of potent anti-rheumatic therapies over the last two decades MRI has gained increasing importance particularly for assessment of disease activity in early stages of several rheumatic disorders. Commonly gadolinium-based contrast agents are used for assessment of synovitis. Due to potential side-effects of gadolinium non-enhanced techniques are desirable that enable visualization of inflammatory disease manifestations. The feasibility of 7 T MRI for evaluation of peripheral arthritis has not been shown up to now. Aim of our study was to evaluate the feasibility of contrast-enhanced (CE) and non-enhanced MRI at 7 T for the assessment of knee joint synovitis. METHOD: Seven T MRI was acquired for 10 patients with an established diagnosis of psoriatic or rheumatoid arthritis. The study pulse sequence protocol was comprised of a sagittal intermediate-weighted fat-suppressed (FS), axial fluid-attenuated inversion recovery (FLAIR) FS, sagittal 3D T1-weighted dynamic contrast enhanced (DCE) and an axial static 2D T1-weighted FS contrast-enhanced sequence (T1-FS CE). Ordinal scoring on non-enhanced (Hoffa- and effusion-synovitis) and enhanced MRI (11-point synovitis score), and comparison of FLAIR-FS with static T1-FS CE MRI using semiquantitative (SQ) grading and volume assessment was performed. For inter- and intra-reader reliability assessment weighted kappa statistics for ordinal scores and intraclass correlation coefficients (ICC) for continuous variables were used. RESULTS: The total length of study protocol was 15 min 38 s. Different amounts of synovitis were observed in all patients (mild: n = 3; moderate: n = 5; severe: n = 2). Consistently, SQ assessment yielded significantly lower peripatellar summed synovitis scores for the FLAIR-FS sequence compared to the CE T1-FS sequence (p < 0.01). FLAIR-FS showed significantly lower peripatellar synovial volumes (p < 0.01) compared to CE T1-FS imaging with an average percentage difference of 18.6 ± 9.5%. Inter- and intra-reader reliability for ordinal SQ scoring ranged from 0.21 (inter-reader Hoffa-synovitis) to 1.00 (inter-reader effusion-synovitis). Inter- and intra-observer reliability of SQ 3D-DCE parameters ranged from 0.86 to 0.99. CONCLUSIONS: Seven T FLAIR-FS ultra-high field MRI is a potential non-enhanced imaging method able to visualize synovial inflammation with high conspicuity and holds promise for further application in research endeavors and clinical routine by trained readers.

T2 Mapping as a New Method for Quantitative Assessment of Cartilage Damage in Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with damage of the articular cartilage and the periarticular bone. While imaging of bone damage has substantially improved in recent years, direct imaging of the articular cartilage of the hand joints in patients with RA is still challenging. The study used T2 mapping of the finger joints to assess cartilage damage in RA. METHODS: Magnetic resonance imaging (MRI) at 3 Tesla was done in 30 patients with RA, and T2 relaxation times visualizing alteration in the collagen network and hydration of articular cartilage were mapped in 6 cartilage regions of the metacarpophalangeal (MCP) joints 2 and 3. Values were related to autoantibody status [anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF)], disease duration, and disease activity as well as sex and age of the patients. RESULTS: T2 relaxation times could be reliably measured in the 6 regions of the MCP joints. Significantly higher relaxation times indicating more advanced cartilage alterations were observed in the metacarpal heads of ACPA-positive (p = 0.001-0.010) and RF-positive patients (p = 0.013-0.025) as well as those with longer disease duration (> 3 yrs; p = 0.028-0.043). Current disease activity, sex, and age did not influence T2 relaxation times. CONCLUSION: These data show that cartilage damage can be localized and quantified in the hand joints of patients with RA by T2 mapping. Further, ACPA and RF positivity as well as disease duration appear to be the crucial factors influencing cartilage damage.

Cost-effective Tapering Algorithm in Patients with Rheumatoid Arthritis: Combination of Multibiomarker Disease Activity Score and Autoantibody Status.

OBJECTIVE: To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)-tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission. METHODS: The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and direct treatment costs were evaluated every 3 months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates. RESULTS: RA patients with a low MBDA score (< 30 units) and negative ACPA showed the lowest relapse risk (19%), while double-positive patients showed high relapse risk (61%). In ACPA-negative and MBDA-negative (< 30 units), and ACPA or MBDA single-positive (> 30 units) groups, DMARD tapering appears feasible. Considering only patients without flare, direct costs for synthetic and biologic DMARD in the ACPA/MBDA-negative and single positive groups (n = 41) would have been €372,245.16 for full-dose treatment over 1 year. Tapering and stopping DMARD in this low-risk relapse group allowed a reduction of €219,712.03 of DMARD costs. Average reduction of DMARD costs per patient was €5358.83. CONCLUSION: Combining MBDA score and ACPA status at baseline may allow risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD in patients in deep remission as defined by the 28-joint count Disease Activity Score using erythrocyte sedimentation rate.

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries.

Objective: To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. Methods: We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach's α and construct validity by Spearman's correlation. Results: A total of 1276 patients participated (76% female, 25% with a disease duration <5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ⩾66% of variation in items explained by each factor and all item factor loadings of 0.71-0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach's α of 0.75-0.96 and for RAID, 0.93-0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63-0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46-0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Conclusion: Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate-good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original.

The structural basis of MRI bone erosions: an assessment by microCT.

OBJECTIVE: To determine whether erosions appearing in MRI in patients with rheumatoid arthritis (RA) represent true erosions. METHODS: 50 RA patients received 1.5 T MRI and microCT (µCT) of the dominant hand. Erosion counts were assessed in coronal T1 weighted MRI sections and in coronal as well as axial µCT sections of the metacarpophalangeal (MCP) joints II-IV. Extent of erosions was assessed by RA MRI Score (RAMRIS) erosion score (MRI) and by three-dimensional assessment of erosion volume (µCT). RESULTS: 111 of the 600 evaluated joint regions showed erosions in the MRI and 137 in the µCT. In only 28 regions false negative lesions (µCT positive, MRI negative) were found, all of which were very small lesions with a volume of less than 10 mm(3). Only two results were false-positive (µCT negative, MRI positive). RAMRIS erosion scores were strongly correlated to erosion volumes in the µCT (Pearson's r=0.514, p<0.001). Mean RAMRIS erosion scores were below 1 with erosion volumes up to 1.5 mm(3), below 2 with erosion volumes up to 20 mm(3) and over 2 with volumes of more than 20 mm(3). DISCUSSION: MRI erosions are generally based on true cortical breaks as shown by µCT. MRI is sensitive to detect bone erosions and only very small lesions escape detection. Moreover, RAMRIS erosion scores are closely linked to the absolute size of bone erosions in the µCT.