Publications by authors named "Ulrich Weber"

84 Publications

Development and Validation of Three Preliminary MRI Sacroiliac Joint Composite Structural Damage Scores in a 5-year Longitudinal Axial Spondyloarthritis Study.

J Rheumatol 2021 Apr 15. Epub 2021 Apr 15.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Soenderborg, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; Department of Rheumatology, Lillebælt Hospital, Vejle, Denmark; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Department of Radiology, Herlev and Gentofte Hospital, Copenhagen, Denmark. The source(s) of support in the form of grants or industrial support: The BIOSPA study was conducted without any financial support. The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. The Danish Rheumatism Association supported MW with a PhD fellowship grant (R131- A5381). Address correspondence to Marie Wetterslev Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases Rigshospitalet, Glostrup Valdemar Hansen Vej 17 Email:

Objective: In axial spondyloarthritis (axSpA), sacroiliac joint (SIJ) erosion is often followed by fat metaplasia in an erosion cavity (backfill), and subsequently ankylosis. We aimed to combine Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ Structural score for Erosion, Backfill and Ankylosis into 3 versions of a novel preliminary Composite axSpA MRI SIJ Structural Damage Score (CSDS) and test these.

Methods: Thirty-three axSpA patients followed for 5 years after initiation of tumor necrosis factor inhibitor had MRI of SIJs at baseline, and yearly thereafter. Three versions of CSDSs were calculated based on different weightings of erosion, backfill and ankylosis: Equal weighting: CSDS=(erosion x0.5)+backfill+ankylosis; Advanced stages weighting more: CSDS=(erosion x1)+(backfill x4)+(ankylosis x6); Advanced stages overruling earlier stages ("hierarchical") with "<" meaning "overruled by": CSDS=(erosion x1)<(backfill x4)<(ankylosis x6).

Results: At baseline all CSDSs correlated positively with SPARCC Fat and Ankylosis, modified New Yorkradiography grading and negatively with BASDAI and SPARCC SIJ Inflammation. CSDS and CSDS (not CSDS) correlated positively with symptom duration and BASMI, and closer with SPARCC ankylosis and Modified New York-radiography grading than CSDS. The adjusted annual progression rate for CSDS and CSDS (not CSDS) was higher the first year compared with fourth year (p=0.04 and p=0.01). Standardized response mean (baselineweek 46) was moderate for CSDS (0.64) and CSDS (0.59) and small for CSDS (0.25).

Conclusion: Particularly CSDS and CSDS showed construct validity and responsiveness, encouraging further validation in larger clinical trials. The potential clinical implication is assessment of sacroiliac joint damage progression by one composite score.
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http://dx.doi.org/10.3899/jrheum.201075DOI Listing
April 2021

Utility of magnetic resonance imaging in Crohn's associated sacroiliitis: A cross-sectional study.

Int J Rheum Dis 2021 Apr 2;24(4):582-590. Epub 2021 Feb 2.

Division of Rheumatology, Department of Medicine, Hospital for Special Surgery, and Weill Cornell Medicine, New York, NY, USA.

Objective: Prevalence of sacroiliitis in Crohn's disease (CD) is variable depending on defining criteria. This study utilized standardized sacroiliac joint (SIJ) magnetic resonance imaging (MRI) to identify sacroiliitis in CD patients and its association with clinical and serological markers.

Methods: Consecutive adult subjects with CD prospectively enrolled from an inflammatory bowel disease clinic underwent SIJ MRI. Data collected included CD duration, history of joint/back pain, human leukocyte antigen-B27 status, Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index, Harvey Bradshaw Index (HBI) for activity of CD, Ankylosing Spondylitis Disease Activity Score, and various serologic markers of inflammation. Three blinded readers reviewed MRIs for active and structural lesions according to the Spondyloarthritis Research Consortium of Canada modules.

Results: Thirty-three CD patients were enrolled: 76% female, 80% White, median age 36.4 years (interquartile range 27.2-49.0), moderate CD activity (mean HBI 8.8 ± SD 4.5). Nineteen subjects (58%) reported any back pain, 13 of whom had inflammatory back pain. Four subjects (12%) showed sacroiliitis using global approach and 6 (18%) met Assessment of SpondyloArthritis international Society MRI criteria of sacroiliitis. Older age (mean 51.2 ± SD 12.5 vs. 37.2 ± 14; P = .04), history of dactylitis (50.0% vs. 3.4%, P = .03) and worse BASMI (4.1 ± 0.7 vs. 2.4 ± 0.8, P ≤ .001) were associated with MRI sacroiliitis; no serologic measure was associated.

Conclusion: There were 12%-18% of CD patients who had MRI evidence of sacroiliitis, which was not associated with back pain, CD activity or serologic measures. This data suggests that MRI is a useful modality to identify subclinical sacroiliitis in CD patients.
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http://dx.doi.org/10.1111/1756-185X.14081DOI Listing
April 2021

Data-Driven Definitions for Active and Structural MRI Lesions in the Sacroiliac Joint in Spondyloarthritis and their Predictive Utility.

Rheumatology (Oxford) 2021 Feb 1. Epub 2021 Feb 1.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark.

Objectives: To determine quantitative sacroiliac joint (SIJ) MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial spondyloarthritis (axSpA) and that predict clinical diagnosis.

Methods: The ASAS MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises: A. 169 cases and 7 central readers; B. 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SIJ quadrants or slices with bone marrow edema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analyzed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPV/NPV) and selecting cut-offs with PPV≥95%.

Results: Active or structural lesions typical of axSpA on MRI had PPV≥95% for clinical diagnosis of axSpA. Cut-offs that best reflect definite active lesion typical of axSpA were either ≥4 SIJ quadrants with BME at any location or at the same location in ≥ 3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥ 3 SIJ quadrants with erosion or ≥ 5 with fat lesion, erosion at the same location for ≥2 consecutive slices, fat lesion at the same location for ≥3 consecutive slices, or presence of a 'deep' (>1cm) fat lesion.

Conclusion: We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPV for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research.
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http://dx.doi.org/10.1093/rheumatology/keab099DOI Listing
February 2021

Ecosystem transpiration and evaporation: Insights from three water flux partitioning methods across FLUXNET sites.

Glob Chang Biol 2020 Dec 6;26(12):6916-6930. Epub 2020 Oct 6.

Institute for Agricultural and Forest Systems in the Mediterranean (ISAFoM), National Research Council of Italy (CNR), Ercolano, Italy.

We apply and compare three widely applicable methods for estimating ecosystem transpiration (T) from eddy covariance (EC) data across 251 FLUXNET sites globally. All three methods are based on the coupled water and carbon relationship, but they differ in assumptions and parameterizations. Intercomparison of the three daily T estimates shows high correlation among methods (R between .89 and .94), but a spread in magnitudes of T/ET (evapotranspiration) from 45% to 77%. When compared at six sites with concurrent EC and sap flow measurements, all three EC-based T estimates show higher correlation to sap flow-based T than EC-based ET. The partitioning methods show expected tendencies of T/ET increasing with dryness (vapor pressure deficit and days since rain) and with leaf area index (LAI). Analysis of 140 sites with high-quality estimates for at least two continuous years shows that T/ET variability was 1.6 times higher across sites than across years. Spatial variability of T/ET was primarily driven by vegetation and soil characteristics (e.g., crop or grass designation, minimum annual LAI, soil coarse fragment volume) rather than climatic variables such as mean/standard deviation of temperature or precipitation. Overall, T and T/ET patterns are plausible and qualitatively consistent among the different water flux partitioning methods implying a significant advance made for estimating and understanding T globally, while the magnitudes remain uncertain. Our results represent the first extensive EC data-based estimates of ecosystem T permitting a data-driven perspective on the role of plants' water use for global water and carbon cycling in a changing climate.
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http://dx.doi.org/10.1111/gcb.15314DOI Listing
December 2020

Drought and heatwave impacts on semi-arid ecosystems' carbon fluxes along a precipitation gradient.

Philos Trans R Soc Lond B Biol Sci 2020 10 7;375(1810):20190519. Epub 2020 Sep 7.

Department Biogeochemical Integration, Max Planck Institute for Biogeochemistry, Hans-Knöll Straße 10, 07745 Jena, Germany.

The inter-annual variability (IAV) of the terrestrial carbon cycle is tightly linked to the variability of semi-arid ecosystems. Thus, it is of utmost importance to understand what the main meteorological drivers for the IAV of such ecosystems are, and how they respond to extreme events such as droughts and heatwaves. To shed light onto these questions, we analyse the IAV of carbon fluxes, its relation with meteorological variables, and the impact of compound drought and heatwave on the carbon cycle of two similar ecosystems, along a precipitation gradient. A four-year long dataset from 2016 to 2019 was used for the FLUXNET sites ES-LMa and ES-Abr, located in central (39°56'25″ N 5°46'28″ W) and southeastern (38°42'6″ N 6°47'9″ W) Spain. We analyse the physiological impact of compound drought and heatwave on the dominant tree species, Our results show that the gross primary productivity of the wetter ecosystem was less sensitive to changes in soil water content, compared to the dryer site. Still, the wetter ecosystem was a source of CO each year, owing to large ecosystem respiration during summer; while the dry site turned into a CO sink during wet years. Overall, the impact of the summertime compound event on annual CO fluxes was marginal at both sites, compared to drought events during spring or autumn. This highlights that drought timing is crucial to determine the annual carbon fluxes in these semi-arid ecosystems. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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http://dx.doi.org/10.1098/rstb.2019.0519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485101PMC
October 2020

A modular dose delivery system for treating moving targets with scanned ion beams: Performance and safety characteristics, and preliminary tests.

Phys Med 2020 Aug 30;76:307-316. Epub 2020 Jul 30.

Biophysics, GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany. Electronic address:

Purpose: The purpose of this study was to develop a modular dose-delivery system (DDS) for scanned-ion radiotherapy that mitigates against organ motion artifacts by synchronizing the motion of the beam with that of the moving anatomy.

Methods: We integrated a new motion synchronization system and an existing DDS into two centers. The modular approach to integration utilized an adaptive layer of software and hardware interfaces. The method of synchronization comprised three major tasks, namely, the creation of 3D treatment plans (each representing one phase of respiratory motion and together comprising a 4D plan), monitoring anatomic motion during treatment, and synchronization of the beam to anatomic motion. The synchronization was accomplished in real time by repeatedly selecting and delivering a 3D plan, i.e., the one that most closely corresponded to the current anatomic state, until all plans were delivered. The performance characteristics of the motion mitigation system were tested by delivering 4D treatment plans to a moving phantom and comparing planned and measured dose distributions. Dosimetric performance was considered acceptable when the gamma-index pass rate was >90%, homogeneity-index value was >95%, and conformity-index value was >60%. Selected safety characteristics were tested by introducing errors during treatment and testing DDS response.

Results: Acceptable dosimetric performance and safety characteristics were observed for all treatment plans.

Conclusions: We demonstrated, for the first time, that a modular prototype system, synchronizing scanned ion beams with moving targets can deliver conformal, motion-compensated dose distributions. The prototype system was implemented and characterized at GSI and CNAO.
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http://dx.doi.org/10.1016/j.ejmp.2020.07.029DOI Listing
August 2020

2D range modulator for high-precision water calorimetry in scanned carbon-ion beams.

Phys Med Biol 2020 10 26;65(21):215003. Epub 2020 Oct 26.

Department of Dosimetry for Radiation Therapy and Diagnostic Radiology, Physikalisch-Technische Bundesanstalt (PTB), Bundesallee 100, D-38116 Braunschweig, Germany. Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany. Department of Physics and Astronomy, University of Heidelberg, Im Neuenheimer Feld 226, D-69120 Heidelberg, Germany.

Ionization chamber-based dosimetry for carbon-ion beams still shows a significantly higher standard uncertainty than high-energy photon dosimetry. This is mainly caused by the high standard uncertainty of the correction factor for beam quality [Formula: see text]. Due to a lack of experimental data, the given values for [Formula: see text] are based on theoretical calculations. To reduce this standard uncertainty, [Formula: see text] factors for different irradiation conditions and ionization chambers (ICs) can be determined experimentally by means of water calorimetry. To perform such measurements in a spread-out Bragg peak (SOBP) for a scanned carbon-ion beam, we describe the process of creating an almost cubic dose distribution of about 6 × 6 × 6 cm using a 2D range modulator. The aim is to achieve a field homogeneity with a standard deviation of measured dose values in the middle of the SOBP (over a lateral range and a depth of about 4 cm) below 2% within a scanning time of under 100 s, applying a dose larger than 1 Gy. This paper describes the optimization and characterization of the dose distribution in detail.
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http://dx.doi.org/10.1088/1361-6560/aba6d5DOI Listing
October 2020

Central reader evaluation of MRI scans of the sacroiliac joints from the ASAS classification cohort: discrepancies with local readers and impact on the performance of the ASAS criteria.

Ann Rheum Dis 2020 07 5;79(7):935-942. Epub 2020 May 5.

Radiology and Diagnostic Imaging and Medical Imaging Consultants, University of Alberta, Edmonton, Alberta, Canada.

Objectives: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group conducted a multireader exercise on MRI scans from the ASAS classification cohort to assess the spectrum and evolution of lesions in the sacroiliac joint and impact of discrepancies with local readers on numbers of patients classified as axial spondyloarthritis (axSpA).

Methods: Seven readers assessed baseline scans from 278 cases and 8 readers assessed baseline and follow-up scans from 107 cases. Agreement for detection of MRI lesions between central and local readers was assessed descriptively and by the kappa statistic. We calculated the number of patients classified as axSpA by the ASAS criteria after replacing local detection of active lesions by central readers and replacing local reader radiographic sacroiliitis by central reader structural lesions on MRI.

Results: Structural lesions, especially erosions, were as frequent as active lesions (≈40%), the majority of patients having both types of lesions. The ASAS definitions for active MRI lesion typical of axSpA and erosion were comparatively discriminatory between axSpA and non-axSpA. Local reader overcall for active MRI lesions was about 30% but this had a minor impact on the number of patients (6.4%) classified as axSpA. Substitution of radiography with MRI structural lesions also had little impact on classification status (1.4%).

Conclusion: Despite substantial discrepancy between central and local readers in interpretation of both types of MRI lesion, this had a minor impact on the numbers of patients classified as axSpA supporting the robustness of the ASAS criteria for differences in assessment of imaging.
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http://dx.doi.org/10.1136/annrheumdis-2020-217232DOI Listing
July 2020

Nutrients and water availability constrain the seasonality of vegetation activity in a Mediterranean ecosystem.

Glob Chang Biol 2020 08 27;26(8):4379-4400. Epub 2020 May 27.

Department for Biogeochemical Integration, Max-Planck-Institute for Biogeochemistry, Jena, Germany.

Anthropogenic nitrogen (N) deposition and resulting differences in ecosystem N and phosphorus (P) ratios are expected to impact photosynthetic capacity, that is, maximum gross primary productivity (GPP ). However, the interplay between N and P availability with other critical resources on seasonal dynamics of ecosystem productivity remains largely unknown. In a Mediterranean tree-grass ecosystem, we established three landscape-level (24 ha) nutrient addition treatments: N addition (NT), N and P addition (NPT), and a control site (CT). We analyzed the response of ecosystem to altered nutrient stoichiometry using eddy covariance fluxes measurements, satellite observations, and digital repeat photography. A set of metrics, including phenological transition dates (PTDs; timing of green-up and dry-down), slopes during green-up and dry-down period, and seasonal amplitude, were extracted from time series of GPP and used to represent the seasonality of vegetation activity. The seasonal amplitude of GPP was higher for NT and NPT than CT, which was attributed to changes in structure and physiology induced by fertilization. PTDs were mainly driven by rainfall and exhibited no significant differences among treatments during the green-up period. Yet, both fertilized sites senesced earlier during the dry-down period (17-19 days), which was more pronounced in the NT due to larger evapotranspiration and water usage. Fertilization also resulted in a faster increase in GPP during the green-up period and a sharper decline in GPP during the dry-down period, with less prominent decline response in NPT. Overall, we demonstrated seasonality of vegetation activity was altered after fertilization and the importance of nutrient-water interaction in such water-limited ecosystems. With the projected warming-drying trend, the positive effects of N fertilization induced by N deposition on GPP may be counteracted by an earlier and faster dry-down in particular in areas where the N:P ratio increases, with potential impact on the carbon cycle of water-limited ecosystems.
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http://dx.doi.org/10.1111/gcb.15138DOI Listing
August 2020

In situ observation of helium and argon release during fluid-pressure-triggered rock deformation.

Sci Rep 2020 Apr 24;10(1):6949. Epub 2020 Apr 24.

Eawag - Swiss Federal Institute for Aquatic Science and Technology, Department of Water Resources and Drinking Water, Ueberlandstrasse 133, 8600, Dübendorf, Switzerland.

Temporal changes in groundwater chemistry can reveal information about the evolution of flow path connectivity during crustal deformation. Here, we report transient helium and argon concentration anomalies monitored during a series of hydraulic reservoir stimulation experiments measured with an in situ gas equilibrium membrane inlet mass spectrometer. Geodetic and seismic analyses revealed that the applied stimulation treatments led to the formation of new fractures (hydraulic fracturing) and the reactivation of natural fractures (hydraulic shearing), both of which remobilized (He, Ar)-enriched fluids trapped in the rock mass. Our results demonstrate that integrating geochemical information with geodetic and seismic data provides critical insights to understanding dynamic changes in fracture network connectivity during reservoir stimulation. The results of this study also shed light on the linkages between fluid migration, rock deformation and seismicity at the decameter scale.
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http://dx.doi.org/10.1038/s41598-020-63458-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181768PMC
April 2020

Serial magnetic resonance imaging and ultrasound examinations demonstrate differential inflammatory lesion patterns in soft tissue and bone upon patient-reported flares in rheumatoid arthritis.

Arthritis Res Ther 2020 02 3;22(1):19. Epub 2020 Feb 3.

Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Engelshøjgade 9A, DK-6400, Sønderborg, Denmark.

Background: Magnetic resonance imaging (MRI) and ultrasonography (US) are more sensitive than clinical evaluation in assessing inflammation in rheumatoid arthritis (RA). Data is scarce regarding potential link between patient-reported flares and inflammation on imaging. The aim of the study was to explore the pattern and longitudinal associations of inflammatory lesions detected by serial MRI and US in relation to patient-reported flares in patients with RA.

Methods: Eighty RA patients with baseline DAS28CRP < 3.2 and no swollen joints were examined at baseline and followed for 1 year. Patients were requested to contact the hospital in case of patient-reported hand flare accompanied by ≥ 1 tender and swollen joint. The 29 patients who reported hand flare had four extra visits within 4 months from flare onset comprising clinical examination, patient-reported outcomes, MRI, and US of wrists and hands. MRI synovitis/tenosynovitis/bone marrow edema (BME) and US synovitis/tenosynovitis were scored. MRI and US scores at and after the flare were compared to baseline before the flare, and associations were explored by linear mixed models for repeated measurements.

Results: Synovitis and tenosynovitis by MRI/US increased significantly at flare onset. Synovitis waned quickly, as did US tenosynovitis. BME showed delayed increase yet persisted, once the patient-reported flare had resolved, as did MRI tenosynovitis. In univariate models, patient-reported flares were associated with all MRI and US inflammatory markers, except for BME, which was only associated with SJC28 and long-lasting flares > 14 days. Independent associations were observed between patient-reported flares and tenosynovitis by MRI and US (p < 0.05).

Conclusions: Patient-reported flares were linked to inflammation detected by serial MRI and US. Differential patterns of inflammatory lesion evolution were observed by serial imaging with early synovial and tenosynovial inflammation, followed by delayed-onset BME.
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http://dx.doi.org/10.1186/s13075-020-2105-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998154PMC
February 2020

TRY plant trait database - enhanced coverage and open access.

Glob Chang Biol 2020 01 31;26(1):119-188. Epub 2019 Dec 31.

Arizona State University, Tempe, AZ, USA.

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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http://dx.doi.org/10.1111/gcb.14904DOI Listing
January 2020

Pain and Self-reported Swollen Joints Are Main Drivers of Patient-reported Flares in Rheumatoid Arthritis: Results from a 12-month Observational Study.

J Rheumatol 2020 09 1;47(9):1305-1313. Epub 2019 Dec 1.

From the Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg; Institute of Regional Health Research, University of Southern Denmark, Odense; Hospital of Southern Jutland, University Hospital of Southern Denmark, Aabenraa; Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, Glostrup; Open Patient data Explorative Network (OPEN), Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Objective: To examine prospectively self-reported flare characteristics and their longitudinal association with disease activity and patient-reported outcomes (PRO) in patients with rheumatoid arthritis (RA).

Methods: Consecutive RA patients with 28-joint count Disease Activity Score based on C-reactive protein (DAS28-CRP) < 3.2 and no swollen joints were examined at baseline, Month 6, and Month 12. Assessments included joint counts, DAS28-CRP, visual analog scale-evaluator's global assessment (EGA), and PRO. Every third month, patients completed the Flare Assessment in Rheumatoid Arthritis and RA Flare Questionnaire, and disclosed self-management strategies. Flaring and non-flaring patients were compared and longitudinal associations between self-reported flare status (yes/no) and disease activity, PRO, and treatment escalation were explored.

Results: Among 80 patients with RA [74% females, mean (SD) age 63 (10) yrs, disease duration 11 (7) yrs, and baseline DAS28-CRP 1.9 (0.6)], 64 (80%) reported flare at least once during 12 months. Fifty-five percent of flares lasted less than 1 week. Common self-management strategies were analgesics (50%) and restricted activities (38%). Patients who reported being in flare had consistently higher disease activity measures and PRO compared to patients without flare. In a partly adjusted model, all flare domains, patient-reported swollen and tender joint counts and disease activity measures were associated with flares. In fully adjusted analyses, present flare was independently associated with pain (OR 1.85, 95% CI 1.34-2.60), patient-reported swollen joints (OR 1.18, 95% CI 1.03-1.36), and higher EGA (OR 1.15, 95% CI 1.04-1.28). Treatment escalation was associated with present flare (p ≤ 0.001).

Conclusion: In RA, self-reported flares were frequent, mainly managed by analgesics, substantiated by higher disease activity measures, independently associated with pain and patient-reported swollen joints, and related to treatment escalation.
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http://dx.doi.org/10.3899/jrheum.190760DOI Listing
September 2020

Canada-Denmark MRI scoring system of the spine in patients with axial spondyloarthritis: updated definitions, scoring rules and inter-reader reliability in a multiple reader setting.

RMD Open 2019 13;5(2):e001057. Epub 2019 Oct 13.

Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada.

Objective: To validate the Canada-Denmark (CANDEN) MRI scoring system for the spine in axial spondyloarthritis with updated lesion definitions.

Methods: Lesion definitions in the CANDEN system were updated and illustrated by a consensus set of reference images. Sagittal spine MRIs of 40 patients with axial spondyloarthritis obtained at baseline and at week 52 after initiation of treatment with the tumour necrosis factor inhibitor golimumab were evaluated in unknown chronology by seven readers blinded to all other data.

Results: CANDEN MRI spine inflammation score had very good reliability for status scores (single-measure intraclass correlation coefficient (ICC) of 21 reader pairs median of 0.91 (IQR 0.88-0.92)) and change scores (ICC 0.88 (0.86-0.92)). CANDEN MRI spine fat score had good to very good reliability for status scores (ICC 0.79 (0.75-0.86)) and moderate to good reliability for detecting change (ICC 0.59 (0.46-0.73)). CANDEN MRI spine bone erosion score and CANDEN MRI spine new bone formation score had slight to moderate reliability for status scores (ICC 0.38 (0.32-0.52) and 0.39 (0.27-0.49), respectively).

Conclusion: The CANDEN MRI spine scoring system allows a comprehensive evaluation of inflammation, fat, bone erosion and new bone formation of the spine in patients with axial spondyloarthritis. It demonstrated very good reliability for detecting change in inflammation, moderate to good reliability for detecting change in fat, and slight to moderate reliability for detecting bone erosions and new bone formation. Studies with longer follow-up or patients with more advanced spinal involvement may be needed to reliably detect change in bone erosion and new bone formation scores.

Trial Registration Number: NCT02011386.
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http://dx.doi.org/10.1136/rmdopen-2019-001057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803003PMC
April 2020

MRI of the sacroiliac joints in athletes: recognition of non-specific bone marrow oedema by semi-axial added to standard semi-coronal scans.

Rheumatology (Oxford) 2020 06;59(6):1381-1390

Department of Rheumatology and Sports Medicine, North Denmark Regional Hospital, Hjørring, Denmark.

Objective: Assessment of combined semi-axial and semi-coronal SI joint MRI in two cohorts of young athletes to explore frequency and topography of non-specific bone marrow oedema (BMO), its association with four constitutional SI joint features, and potential restriction of false-positive assignments of Assessment of SpondyloArthritis International Society-defined sacroiliitis on standard semi-coronal scans alone.

Methods: Combined semi-axial and semi-coronal SI joint MRI scans of 20 recreational runners before/after running and 22 elite ice-hockey players were evaluated by three blinded readers for BMO and its association with four constitutional SI joint features: vascular partial volume effect, deep iliac ligament insertion, fluid-filled bone cyst and lumbosacral transitional anomaly. Scans of TNF-treated spondyloarthritis patients served to mask readers. We analysed distribution and topography of BMO and SI joint features across eight anatomical SI joint regions (upper/lower ilium/sacrum, subdivided in anterior/posterior slices) descriptively, as concordantly recorded by ⩾2/3 readers on both MRI planes. BMO confirmed on both scans was compared with previous evaluation of semi-coronal MRI alone, which met the Assessment of SpondyloArthritis International Society definition for active sacroiliitis.

Results: Perpendicular semi-axial and semi-coronal MRI scans confirmed BMO in the SI joint of every fourth young athlete, preferentially in the anterior upper sacrum. BMO associated with four constitutional SI joint features was observed in 20-36% of athletes, clustering in the posterior lower ilium. The proportion of Assessment of SpondyloArthritis International Society-positive sacroiliitis recorded on the semi-coronal plane alone decreased by 33-56% upon amending semi-axial scans.

Conclusion: Semi-axial combined with standard semi-coronal scans in MRI protocols for sacroiliitis facilitated recognition of non-specific BMO, which clustered in posterior lower ilium/anterior upper sacrum.
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http://dx.doi.org/10.1093/rheumatology/kez458DOI Listing
June 2020

MRI lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the ASAS MRI working group.

Ann Rheum Dis 2019 11 17;78(11):1550-1558. Epub 2019 Aug 17.

Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Herne, Germany.

Objectives: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint (SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation.

Methods: The literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC).

Results: No revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97).

Conclusion: The ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.
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http://dx.doi.org/10.1136/annrheumdis-2019-215589DOI Listing
November 2019

Flares in rheumatoid arthritis: do patient-reported swollen and tender joints match clinical and ultrasonography findings?

Rheumatology (Oxford) 2020 01;59(1):129-136

Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark.

Objectives: To investigate how patient-reported flares in RA are related to clinical joint examination and inflammation detected by US.

Methods: Eighty RA patients with DAS28-CRP <3.2 and no swollen joints at baseline were followed for 1 year. In case of patient-reported hand flare with swollen and tender joints (SJ and TJ, respectively), patients underwent clinical examination for SJ/TJ and US of bilateral wrists, MCP and PIP 1st-5th, six extensor tendon compartments and wrist flexor tendons for synovitis/tenosynovitis. Percentage agreement and kappa were calculated between patient-reported SJ and TJ, clinical examination for SJ/TJ and US findings indicative of inflammation. With US as reference, sensitivity, specificity, positive/negative predictive value and accuracy of patient-reported and clinically examined joints were determined.

Results: Hand flare was reported by 36% (29/80) of patients. At time of flare, all clinical and ultrasonographic measures of disease activity deteriorated compared with baseline. Agreement between patient-reported SJ/TJ, clinically examined SJ/TJ and US was slight (kappa = 0.02-0.20). Patients and clinicians agreed in 79-93% of joints, more frequently on SJ than TJ. With US as reference, specificities were 86-100% and 88-100%, and sensitivities 12-34% and 4-32% for patient-reported SJ/TJ and clinically examined SJ/TJ, respectively.

Conclusion: Over 12 months of follow-up, hand flare was reported by every third RA patient. Self-reported flares were associated with increased disease activity as determined by clinical examination and US. Patient-reported joint assessment may aid in capturing flares between routine clinical visits.
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http://dx.doi.org/10.1093/rheumatology/kez231DOI Listing
January 2020

What Level of Inflammation Leads to Structural Damage in the Sacroiliac Joints? A Four-Year Magnetic Resonance Imaging Follow-Up Study of Low Back Pain Patients.

Arthritis Rheumatol 2019 12 9;71(12):2027-2033. Epub 2019 Nov 9.

Hospital Lillebaelt, Middelfart, Denmark, University of Southern Denmark, Odense, Denmark, and Aarhus University Hospital and Aarhus University, Aarhus N, Denmark.

Objective: Sacroiliac (SI) joint bone marrow edema (BME) is considered to be pivotal in the detection of early spondyloarthritis. However, the link between BME and development of spondyloarthritis-related bone remodeling remains unclear. This study was undertaken to investigate the evolution of BME and structural lesions in the SI joints over time.

Methods: Baseline and 4-year follow-up magnetic resonance imaging scans were conducted in 604 patients ages 18-40 years who were referred with low back pain to an outpatient spine clinic. Eight SI joint regions were scored for BME and categorized as absent, limited (<25% of subcortical bone region), intermediate (25-50%), or extensive (>50%). Structural lesions including erosions and fat lesions were scored as absent or present.

Results: SI joint BME was seen at either time point (baseline or at 4 years) in 41% of participants but was persistent at both time points in only 16% of participants. Structural SI joint lesions developed according to the extent of BME at baseline: limited, intermediate, and extensive BME (as compared to absent BME) were independently associated with erosion at follow-up with odds ratios (ORs) of 3, 5, and 46, respectively, and with fat lesions (ORs 3, 7, and 33, respectively). In regions with limited and intermediate BME at baseline, 60% and 50% had resolved by follow-up, respectively, while only 2% and 7% had evolved into extensive BME by follow-up.

Conclusion: While extensive SI joint BME was a strong independent predictor of development of structural lesions, limited and intermediate BME were mostly transient and only rarely evolved into extensive BME or structural lesions. These findings enhance our understanding of the natural development of SI joint lesions and indicate different progression patterns for limited/intermediate versus extensive BME, possibly due to different etiologies.
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http://dx.doi.org/10.1002/art.41040DOI Listing
December 2019

Imaging in axial spondyloarthritis: Changing concepts and thresholds.

Best Pract Res Clin Rheumatol 2018 06 17;32(3):342-356. Epub 2018 Nov 17.

Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Claudiusstrasse 45, 44649, Herne, Germany. Electronic address:

Imaging is key to recognition of axial spondyloarthritis (SpA) because clinical and laboratory examinations have limited diagnostic utility. Only MRI can capture both inflammation and bone remodeling by simultaneous depiction of active and structural lesions and their anatomic location. Bone marrow edema of limited extent on the sacroiliac joint (SIJ) MRI is often nonspecific and should be interpreted along with the clinical context. Contextual interpretation of the SIJ lesion signature viewed simultaneously on fluid- and fat-sensitive MRI sequences enhances confidence in the recognition of disease. A critical re-appraisal of using pelvic radiographs in clinically suspected early spondyloarthritis is warranted because of substantial limitations. In health care settings with low threshold access to advanced imaging, MRI is the preferred modality in early SpA. CT has recently advanced spinal outcome research, but substantial radiation exposure in young patients with spondyloarthritis and limited evidence on its relevance in practice do not advocate its use in daily routine.
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http://dx.doi.org/10.1016/j.berh.2018.10.009DOI Listing
June 2018

The FLUXCOM ensemble of global land-atmosphere energy fluxes.

Sci Data 2019 May 27;6(1):74. Epub 2019 May 27.

Max Planck Institute for Biogeochemistry, Hans-Knöll-Str. 10, 07745, Jena, Germany.

Although a key driver of Earth's climate system, global land-atmosphere energy fluxes are poorly constrained. Here we use machine learning to merge energy flux measurements from FLUXNET eddy covariance towers with remote sensing and meteorological data to estimate global gridded net radiation, latent and sensible heat and their uncertainties. The resulting FLUXCOM database comprises 147 products in two setups: (1) 0.0833° resolution using MODIS remote sensing data (RS) and (2) 0.5° resolution using remote sensing and meteorological data (RS + METEO). Within each setup we use a full factorial design across machine learning methods, forcing datasets and energy balance closure corrections. For RS and RS + METEO setups respectively, we estimate 2001-2013 global (±1 s.d.) net radiation as 75.49 ± 1.39 W m and 77.52 ± 2.43 W m, sensible heat as 32.39 ± 4.17 W m and 35.58 ± 4.75 W m, and latent heat flux as 39.14 ± 6.60 W m and 39.49 ± 4.51 W m (as evapotranspiration, 75.6 ± 9.8 × 10 km yr and 76 ± 6.8 × 10 km yr). FLUXCOM products are suitable to quantify global land-atmosphere interactions and benchmark land surface model simulations.
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http://dx.doi.org/10.1038/s41597-019-0076-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536554PMC
May 2019

A new facility for proton radiobiology at the Trento proton therapy centre: Design and implementation.

Phys Med 2019 Feb 11;58:99-106. Epub 2019 Feb 11.

Trento Institute for Fundamental Physics and Applications (TIFPA), National Institute for Nuclear Physics, INFN, Povo, Italy.

We present a new facility dedicated to radiobiology research, which has been implemented at the Trento Proton Therapy Centre (Italy). A dual-ring double scattering system was designed to produce irradiation fields of two sizes (i.e. 6 and 16 cm diameter) starting from a fix pencil beam at 148 MeV. The modulation in depth was obtained with a custom-made range modulator, optimized to generate a 2.5 cm spread-out Bragg peak (SOBP). The resulting irradiation field was characterized in terms of lateral and depth-dose profiles. The beam characteristics and the geometry of the setup were implemented in the Geant4 Monte Carlo (MC) code. After benchmark against experimental data, the MC was used to characterize the distribution of dose-average linear energy transfer (LET) associated to the irradiation field. The results indicate that dose uniformity above 92.9% is obtained at the entrance channel as well as in the middle SOBP in the target regions for both irradiation fields. Dose rate in the range from 0.38 to 0.78 Gy/min was measured, which can be adjusted by proper selection of cyclotron output current, and eventually increased by about a factor 7. MC simulations were able to reproduce experimental data with good agreement. The characteristics of the facility are in line with the requirements of most radiobiology experiments. Importantly, the facility is also open to external users, after successful evaluation of beam proposals by the Program Advisory Committee.
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http://dx.doi.org/10.1016/j.ejmp.2019.02.001DOI Listing
February 2019

OMERACT Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) Assessment in Longitudinal Study.

J Rheumatol 2019 09 15;46(9):1239-1242. Epub 2019 Feb 15.

From the Department of Radiology and Diagnostic Imaging, University of Alberta; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Rigshospitalet-Glostrup, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen; King Christian 10th Hospital for Rheumatic Diseases, Gråsten; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; St. Vincent's Hospital, Melbourne, Australia.

Objective: To assess reliability, feasibility, and responsiveness of Hip Inflammation Magnetic resonance imaging Scoring System (HIMRISS) for bone marrow lesions (BML) in hip osteoarthritis (OA).

Methods: HIMRISS was scored by 8 readers in 360 hips of 90 patients imaged pre/post-hip steroid injection. Pre-scoring, new readers trained online to achieve intraclass correlation coefficient (ICC) > 0.80 versus experts.

Results: HIMRISS reliability was excellent for BML status (ICC 0.83-0.92). Despite small changes post-injection, reliability of BML change scores was high in femur (0.76-0.81) and moderate in acetabulum (0.42-0.56).

Conclusion: HIMRISS should be a priority for further assessment of hip BML in OA, and evaluated for use in other arthropathies.
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http://dx.doi.org/10.3899/jrheum.181043DOI Listing
September 2019

A Novel Approach To Quantify Air-Water Gas Exchange in Shallow Surface Waters Using High-Resolution Time Series of Dissolved Atmospheric Gases.

Environ Sci Technol 2019 02 14;53(3):1463-1470. Epub 2019 Jan 14.

Centre Européen de Recherche et d'Enseignement des Géosciences de l'Environnement (CEREGE), CNRS, IRD, INRA , Coll France , Aix en Provence 13545 , France.

Gas exchange across the air-water interface is a key process determining the release of greenhouse gases from surface waters and a fundamental component of gas dynamics in aquatic systems. To experimentally quantify the gas transfer velocity in a wide range of aquatic settings, a novel method based on recently developed techniques for the in situ, near-continuous measurement of dissolved (noble) gases with a field portable mass spectrometer is presented. Variations in observed dissolved gas concentrations are damped and lagged with respect to equilibrium concentrations, being the result of (a) temperature (and thus solubility) variations, (b) water depth, and (c) the specific gas transfer velocity ( k). The method fits a model to the measured gas concentrations to derive the gas transfer velocity from the amplitude and the phase lag between observed and equilibrium concentrations. With the current experimental setup, the method is sensitive to gas transfer velocities of 0.05-9 m/day (for N), at a water depth of 1 m, and a given daily water temperature variation of 10 °C. Experiments were performed (a) in a controlled experiment to prove the concept and to confirm the capability to determine low transfer velocities and (b) in a field study in a shallow coastal lagoon covering a range of transfer velocities, demonstrating the field applicability of the method.
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http://dx.doi.org/10.1021/acs.est.8b05318DOI Listing
February 2019

Do Patients With Skin Psoriasis Show Subclinical Axial Inflammation on Magnetic Resonance Imaging of the Sacroiliac Joints and Entire Spine?

Arthritis Care Res (Hoboken) 2019 08;71(8):1109-1118

University Hospital Basel, Basel, Switzerland.

Objective: To explore potential subclinical involvement of the axial skeleton by magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and the entire spine in patients with skin psoriasis without clinical evidence of peripheral or axial inflammation.

Methods: Twenty patients with skin psoriasis but no clinical evidence of peripheral or axial inflammation and 22 healthy controls underwent standardized dermatologic and rheumatologic clinical examination and unenhanced 1.5T MRI of the SI joint and the entire spine. Two blinded readers globally assessed the presence or absence of SI joint inflammation simultaneously on T1-weighted and short tau inversion recovery MRI sequences with a confidence estimate. Bone marrow edema, fat metaplasia, erosion, and ankylosis of the SI joint, and vertebral corner inflammatory lesions and fat lesions were recorded using standardized modules. The prevalence of each lesion type was calculated in both groups, averaged across 2 readers. The number of subjects with lesions in the SI joint and spine (≥1, 2, 3, 4, or 5 lesions) as concordantly assessed by both readers was recorded.

Results: The median duration of skin psoriasis was 23.0 years, the median age of patients was 48.5 years, and 25.0% of patients and 9.1% of healthy controls were concordantly classified by both readers as having SI joint inflammation (P = 0.23). The prevalence of bone marrow edema and structural lesions was comparable across patients and controls, both on SI joint and spine MRI.

Conclusion: In this controlled study, patients with skin psoriasis but no clinical arthritis or spondylitis showed limited evidence of concomitant subclinical axial involvement by SI joint and spine MRI. These findings do not support routine screening for subclinical axial inflammation in patients with longstanding skin psoriasis.
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http://dx.doi.org/10.1002/acr.23767DOI Listing
August 2019

MRI in spondyloarthritis: when and how?

Curr Opin Rheumatol 2018 07;30(4):324-333

King Christian 10th Hospital for Rheumatic Diseases, Gråsten.

Purpose Of Review: To summarize recent advances and challenges of using MRI toward early recognition of axial spondyloarthritis (SpA).

Recent Findings: Low-grade bone marrow edema (BME) on sacroiliac joint (SIJ) MRI is nonspecific and may be misleading in recognition of axial SpA. Structural features on SIJ MRI along with BME may not only facilitate recognition of early disease, but also enhance specificity. Structural lesions on MRI and low-dose computed tomography are highly concordant, adding to criterion validity of SIJ MRI. There is accumulating evidence that SIJ MRI due to superior reliability of structural lesions may supplant the traditional imaging approach by pelvic radiographs in healthcare settings in which MRI is readily available. Pilot initiatives exploring the bone remodeling cascade in SIJs showed early reparative response upon biological treatment. Methodological challenges regarding evaluation and data processing of imaging examinations need to be addressed to enhance reproducibility and specificity of imaging in SpA.

Summary: Evaluation of SIJ MRI is contextual incorporating structural lesions and BME. MRI is but one element in pattern recognition toward diagnosis. An unmet need is dissemination of advances in imaging in SpA to the broad community of rheumatologists and radiologists.
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http://dx.doi.org/10.1097/BOR.0000000000000512DOI Listing
July 2018

MRI for diagnosis of axial spondyloarthritis: major advance with critical limitations 'Not everything that glisters is gold (standard)'.

RMD Open 2018 12;4(1):e000586. Epub 2018 Jan 12.

King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark.

Recognition of axial spondyloarthritis (SpA) remains challenging, as no unique reference standard is available to ascertain diagnosis. Imaging procedures have been used for long in the field, in particular pelvic radiography, to capture structural changes evocative of sacroiliitis, the key feature in SpA. The introduction of MRI of the sacroiliac joints (SIJs) has led to a major shift in recognition of the disorder. MRI has been shown to detect the initial inflammatory processes, in particular osteitis depicted by bone marrow oedema, even in patients having not yet developed structural lesions. In addition, MRI has revealed a previously under-recognised very early clinical phase of the disease where patients have symptomatic axial involvement, but no structural changes. However, what constitutes a 'positive MRI' in SpA remains controversial, since both sensitivity and specificity show limitations, and interpretation of MRI lesions in daily practice is critically dependent on the clinical context. There is growing evidence that integration of the assessment of structural changes on dedicated T1 weighted-sequences on MRI may enhance diagnostic utility. The performance of MRI in detecting structural lesions in the SIJs may even be superior to traditional evaluation by pelvic radiography. These findings launched a debate on imaging in SpA, whether MRI, which is advancing early recognition of disease and shows superiority to detect structural changes, should replace traditional conventional radiography of the SIJs.
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http://dx.doi.org/10.1136/rmdopen-2017-000586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822619PMC
January 2018

Response to Tumor Necrosis Factor Inhibition in Male and Female Patients with Ankylosing Spondylitis: Data from a Swiss Cohort.

J Rheumatol 2018 04 15;45(4):506-512. Epub 2018 Feb 15.

From the Swiss Clinical Quality Management Foundation; Department of Rheumatology, Zurich University Hospital, Zurich; Praxis Rheuma-Basel, Basel, Switzerland; King Christian 10th Hospital for Rheumatic Diseases, Gråsten; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; Ultrasound Center Rheumatology, Basel; Department of Rheumatology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne; Department of Rheumatology, University Hospital, Geneva; Department of Rheumatology and Clinical Immunology, Inselspital, Bern; Department of Rheumatology and Rehabilitation, Bürgerspital, Solothurn, Switzerland; Department of Rheumatology, VU University Medical Center, Amsterdam, the Netherlands; Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin, Berlin, Germany; Department of Clinical Immunology and Rheumatology, University of Amsterdam; Department of Rheumatology, Zuyderland Hospital, Heerlen; Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.

Objective: To investigate sex differences in connection with the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS).

Methods: A total of 440 patients with AS (294 men; 146 women) initiating a first TNFi in the prospective Swiss Clinical Quality Management Cohort were included. We evaluated the proportion of patients achieving the 20% and 40% improvement in the Assessment of Spondyloarthritis international Society criteria (ASAS20 and ASAS40) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued TNFi were considered nonresponders. Logistic regression analyses were performed to adjust for important predictors of response.

Results: Compared to men, female patients had lower mean C-reactive protein levels, better spinal mobility, and more peripheral disease at the start. There was no sex disparity with regard to the ASDAS, the Bath Ankylosing Spondylitis Disease Activity and Functional indices, and the quality of life. At 1 year, 52% of women and 63% of men achieved an ASAS20 response (OR 0.63, 95% CI 0.37-1.07, p = 0.09). An inactive disease status (ASDAS < 1.3) was reached by 18% of women and 26% of men (OR 0.65, 95% CI 0.32-1.27, p = 0.22). These sex differences in response to TNFi were more pronounced in adjusted analyses (OR 0.34, 95% CI 0.16-0.71, p = 0.005 for ASAS20 and OR 0.10, 95% CI 0.03-0.31, p < 0.001 for ASDAS < 1.3) and confirmed for all the other outcomes assessed.

Conclusion: In AS, fewer women respond to TNFi and women show a reduced response in comparison to men.
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http://dx.doi.org/10.3899/jrheum.170166DOI Listing
April 2018

Frequency and Anatomic Distribution of Magnetic Resonance Imaging Features in the Sacroiliac Joints of Young Athletes: Exploring "Background Noise" Toward a Data-Driven Definition of Sacroiliitis in Early Spondyloarthritis.

Arthritis Rheumatol 2018 05 23;70(5):736-745. Epub 2018 Mar 23.

North Denmark Regional Hospital, Hjørring, Denmark.

Objective: Low-grade bone marrow edema (BME) has been reported in the sacroiliac (SI) joints of 25% of healthy individuals and patients with nonspecific mechanical back pain, thus challenging the specificity and predictive value of magnetic resonance imaging (MRI) for the discrimination of early spondyloarthritis (SpA). It is unknown whether stress injury in competition sports may trigger BME. This study sought to explore the frequency and anatomic distribution of SI joint MRI lesions in recreational and elite athletes.

Methods: After pretest calibration, semicoronal MRI scans of the SI joints of 20 recreational runners before and after running and 22 elite ice hockey players were assessed for BME and structural lesions. Three readers assessed the MRI scans in a blinded manner, using an SI joint quadrant-based module; scans from tumor necrosis factor inhibitor-treated patients with SpA served for masking. The readers recorded subjects who met the Assessment of SpondyloArthritis international Society (ASAS) definition of active sacroiliitis. For descriptive analysis, the frequency of SI joint quadrants exhibiting BME and structural lesions, as concordantly recorded by ≥2 of 3 readers, and their distribution in 8 anatomic SI joint regions (the upper and lower ilium and sacrum, subdivided in anterior and posterior slices) were determined.

Results: The proportions of recreational runners and elite ice hockey players fulfilling the ASAS definition of active sacroiliitis, as recorded concordantly by ≥2 of 3 readers, were 30-35% and 41%, respectively. In recreational runners before and after running, the mean ± SD number of SI joint quadrants showing BME was 3.1 ± 4.2 and 3.1 ± 4.5, respectively, while in elite ice hockey players, it was 3.6 ± 3.0. The posterior lower ilium was the single most affected SI joint region, followed by the anterior upper sacrum. Erosion was virtually absent.

Conclusion: In recreational and elite athletes, MRI revealed BME in an average of 3-4 SI joint quadrants, meeting the ASAS definition of active sacroiliitis in 30-41% of subjects. The posterior lower ilium was the single most affected SI joint region. These findings in athletes could help refine data-driven thresholds for defining sacroiliitis in early SpA.
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http://dx.doi.org/10.1002/art.40429DOI Listing
May 2018

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

Ann Rheum Dis 2018 Jan 22;77(1):63-69. Epub 2017 Sep 22.

Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.

Objectives: To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS).

Methods: Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis.

Results: A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97).

Conclusion: TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.
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http://dx.doi.org/10.1136/annrheumdis-2017-211544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754737PMC
January 2018

Hip Inflammation MRI Scoring System (HIMRISS) to predict response to hyaluronic acid injection in hip osteoarthritis.

Joint Bone Spine 2018 07 8;85(4):475-480. Epub 2017 Sep 8.

Department of Rheumatology, CHRU de Nancy, 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.

Objective: To assess predictors of response, according to hip MRI inflammatory scoring system (HIMRISS), in a sample of patients with hip osteoarthritis (OA) treated by hyaluronic acid (HA) injection.

Method: Sixty patients with hip OA were included. Clinical outcomes were assessed at baseline and three months after HA injection by WOMAC. On hip MRI performed before HA injection, bone marrow lesion (BML) and synovitis were assessed by HIMRISS by four readers. The inter-reader reliability of HIMRISS was for HIMRISS total, acetabular BML, femoral BML and synovitis-effusion respectively 0.86, 0.64, 0.83 and 0.78. Associations between MRI features and clinical data were assessed. Logistic regression (univariate and multivariate) was used to explore associations between MRI features and response to HA injection, according to WOMAC50 response at three months.

Results: In total, 45.5% of patients met WOMAC50 response. Five adverse events were reported. At baseline, WOMAC function correlated significantly to HIMRISS synovitis-effusion (r=0.27, P=0.03). In univariate analysis, BML femoral according to binary assessment (P=0.025), HIMRISS BML femoral (P=0.0038), HIMRISS BML acetabular (P=0.042), HIMRISS total (P=0.0092) were associated negatively with WOMAC50 response. In multivariate analysis, adjusted for age and BMI, HIMRISS femoral BML (P=0.02) and HIMRISS total (P=0.016) were negatively associated with response. At a HIMRISS threshold of<15, 82% of patients were responders, with specificity SP=0.97, sensitivity SN=0.39, and positive and negative predictive values of 0.91 and 0.64, respectively.

Conclusion: HIMRISS is reliable for total scores and sub-domains. It permits identification of responders to HA injection in hip OA patients.
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http://dx.doi.org/10.1016/j.jbspin.2017.08.004DOI Listing
July 2018