Interobserver Agreement and Performance of Concurrent AI Assistance for Radiographic Evaluation of Knee Osteoarthritis.

Background Due to conflicting findings in the literature, there are concerns about a lack of objectivity in grading knee osteoarthritis (KOA) on radiographs. Purpose To examine how artificial intelligence (AI) assistance affects the performance and interobserver agreement of radiologists and orthopedists of various experience levels when evaluating KOA on radiographs according to the established Kellgren-Lawrence (KL) grading system. Materials and Methods In this retrospective observer performance study, consecutive standing knee radiographs from patients with suspected KOA were collected from three participating European centers between April 2019 and May 2022. Each center recruited four readers across radiology and orthopedic surgery at in-training and board-certified experience levels. KL grading (KL-0 = no KOA, KL-4 = severe KOA) on the frontal view was assessed by readers with and without assistance from a commercial AI tool. The majority vote of three musculoskeletal radiology consultants established the reference standard. The ordinal receiver operating characteristic method was used to estimate grading performance. Light kappa was used to estimate interrater agreement, and bootstrapped t statistics were used to compare groups. Results Seventy-five studies were included from each center, totaling 225 studies (mean patient age, 55 years ± 15 [SD]; 113 female patients). The KL grades were KL-0, 24.0% (n = 54); KL-1, 28.0% (n = 63); KL-2, 21.8% (n = 49); KL-3, 18.7% (n = 42); and KL-4, 7.6% (n = 17). Eleven readers completed their readings. Three of the six junior readers showed higher KL grading performance with versus without AI assistance (area under the receiver operating characteristic curve, 0.81 ± 0.017 [SEM] vs 0.88 ± 0.011 [P < .001]; 0.76 ± 0.018 vs 0.86 ± 0.013 [P < .001]; and 0.89 ± 0.011 vs 0.91 ± 0.009 [P = .008]). Interobserver agreement for KL grading among all readers was higher with versus without AI assistance (κ = 0.77 ± 0.018 [SEM] vs 0.85 ± 0.013; P < .001). Board-certified radiologists achieved almost perfect agreement for KL grading when assisted by AI (κ = 0.90 ± 0.01), which was higher than that achieved by the reference readers independently (κ = 0.84 ± 0.017; P = .01). Conclusion AI assistance increased junior readers' radiographic KOA grading performance and increased interobserver agreement for osteoarthritis grading across all readers and experience levels. Published under a CC BY 4.0 license. Supplemental material is available for this article.

CT in musculoskeletal imaging: still helpful and for what?

Computed tomography (CT) is a common modality employed for musculoskeletal imaging. Conventional CT techniques are useful for the assessment of trauma in detection, characterization and surgical planning of complex fractures. CT arthrography can depict internal derangement lesions and impact medical decision making of orthopedic providers. In oncology, CT can have a role in the characterization of bone tumors and may elucidate soft tissue mineralization patterns. Several advances in CT technology have led to a variety of acquisition techniques with distinct clinical applications. These include four-dimensional CT, which allows examination of joints during motion; cone-beam CT, which allows examination during physiological weight-bearing conditions; dual-energy CT, which allows material decomposition useful in musculoskeletal deposition disorders (e.g., gout) and bone marrow edema detection; and photon-counting CT, which provides increased spatial resolution, decreased radiation, and material decomposition compared to standard multi-detector CT systems due to its ability to directly translate X-ray photon energies into electrical signals. Advanced acquisition techniques provide higher spatial resolution scans capable of enhanced bony microarchitecture and bone mineral density assessment. Together, these CT acquisition techniques will continue to play a substantial role in the practices of orthopedics, rheumatology, metabolic bone, oncology, and interventional radiology.

Tendon Elongation and Function After Delayed or Standard Loading of Surgically Repaired Achilles Tendon Ruptures: A Randomized Controlled Trial.

BACKGROUND: Achilles tendon ruptures often result in long-term functional deficits despite accelerated (standard) rehabilitation. PURPOSE/HYPOTHESIS: The purpose of this study was to investigate if delayed loading would influence functional, clinical, and structural outcomes of the muscles and tendon 1 year after a surgical repair. It was hypothesized that delaying the loading would reduce the heel-rise height deficit 1 year after Achilles tendon rupture. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In total, 48 patients with a surgically repaired Achilles tendon rupture were randomized to 2 groups: the standard group received the currently accepted rehabilitation, and the delayed group received the same rehabilitation except that initial loading was delayed by 6 weeks. The primary outcome was the heel-rise height difference between the injured and uninjured sides at 1 year. The secondary outcomes were (1) tendon length measured with magnetic resonance imaging, (2) muscle fascicle length and pennation angle of the gastrocnemius medialis muscle, (3) Doppler activity measured with ultrasonography, (4) Achilles tendon Total Rupture Score (ATRS), and (5) isometric muscle strength. RESULTS: The mean heel-rise height deficits for the standard and delayed groups were -2.2 cm and -2.1 cm, respectively (P = .719). The soleus part of the tendon was already elongated 1 week after surgery in both groups without a between-group difference (side-to-side difference: standard, 16.3 mm; delayed, 17.5 mm; P = .997) and did not change over 52 weeks. The gastrocnemius tendon length was unchanged at 1 week but elongated over time without a between-group difference (side-to-side difference at 52 weeks: standard, 10.5 mm; delayed, 13.0 mm; P = .899). The delayed group had less Doppler activity at 12 weeks (P = .006) and a better ATRS (standard, 60 points; delayed, 72 points; P = .032) at 52 weeks. CONCLUSION: Delayed loading was not superior to standard loading in reducing the heel-rise height difference at 1 year. The data indirectly suggested reduced inflammation in the initial months and a better patient-reported outcome at 1 year in the delayed group. The soleus part of the tendon was already markedly elongated (35%) 1 week after surgery, while the length of the gastrocnemius tendon was unchanged at 1 week but was 6% elongated at 1 year. Together, these data indirectly suggest that the delayed group fared better, although this finding needs to be confirmed in future investigations. REGISTRATION: NCT04263493 (ClinicalTrials.gov identifier).

Two-year MRI-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults.

OBJECTIVE: To investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear. METHODS: A secondary analysis of a multicentre randomised controlled trial including 121 patients (18-40 years) with an MRI-verified meniscal tear. For this study, only patients with 2-year follow-up were included. The main outcomes were the difference in worsening of structural knee damage, assessed by MRI using the Anterior Cruciate Ligament OsteoArthrits Score, and the difference in change in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, from baseline to 2 years. RESULTS: In total, 82/121 (68%) patients completed the 2-year follow-up (39 from the surgical group and 43 from the exercise group). MRI-defined cartilage damage had developed or progressed in seven (9.1%) patients and osteophytes developed in two (2.6%) patients. The worsening of structural damage from baseline to 2-year follow-up was similar between groups. The mean (95% CI) adjusted differences in change in KOOS4 between intervention groups from baseline to 2 years was -1.4 (-9.1, 6.2) points. The mean improvement in KOOS4 was 16.4 (10.4, 22.4) in the surgical group and 21.5 (15.0, 28.0) in the exercise group. No between group differences in improvement were found in the KOOS subscales. CONCLUSIONS: The 2-year worsening of MRI-defined structural damage was limited and similar in young adult patients with a meniscal tear treated with surgery or exercise with optional delayed surgery. Both groups had similar clinically relevant improvements in KOOS4, suggesting the choice of treatment strategy does not impact 2-year structural knee damage or PROMs. TRIAL REGISTRATION NUMBER: NCT02995551.

Occurrence and Prediction of Flare After Tapering of Tumor Necrosis Factor Inhibitors in Patients With Axial Spondyloarthritis.

OBJECTIVE: Patients with axial spondyloarthritis (axSpA) in clinical remission tapered tumor necrosis factor inhibitor (TNFi) therapy according to a clinical guideline. Over a 2-year follow-up period, we aimed to investigate flare frequency, dose at which flare occurred, type of flare, and predictors thereof. METHODS: Patients in clinical remission (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] < 40, physician global score < 40, and without disease activity the previous year) tapered TNFi to two-thirds the standard dose at baseline, half at week 16, one-third at week 32, and discontinued at week 48. Flares were defined as BASDAI flare (BASDAI ≥ 40 and change ≥ 20 since inclusion), and/or clinical flare (development of inflammatory back pain, musculoskeletal or extraarticular manifestations, and/or Ankylosing Spondylitis Disease Activity Score [ASDAS] ≥ 0.9), and/or magnetic resonance imaging (MRI) flare (≥ 2 new or worsened inflammatory lesions). RESULTS: Of 108 patients, 106 (99%) flared before 2-year follow-up: 29 patients (27%) at two-thirds standard dose, 21 (20%) at half dose, 29 (27%) at one-third dose, and 27 (25%) after discontinuation. Regarding type of flare, 105 (99%) had clinical flares, 25 (24%) had BASDAI flares, and 23 (29% of patients with MRI at flare available) had MRI flares. Forty-one patients (41%) fulfilled the Assessment of SpondyloArthritis international Society (ASAS) definition of clinically important worsening (≥ 0.9 increase since baseline). Higher baseline physician global score was an independent predictor of flare after tapering to two-thirds (OR 1.19, 95% CI 1.04-1.41, P = 0.01). Changes in clinical and/or imaging variables in the 16 weeks prior to tapering did not predict flare. CONCLUSION: Almost all (99%) patients with axSpA in clinical remission experienced flare during tapering to discontinuation, but in over half of these patients, flare did not occur before receiving one-third dose or less. Higher physician global score was an independent predictor of flare.

Effect of Curcuma longa extract on serum inflammatory markers and MRI-based synovitis in knee osteoarthritis: secondary analyses from the CurKOA randomised trial.

BACKGROUND: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. PURPOSE: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. METHODS: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. RESULTS: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. CONCLUSION: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.

Genome-wide association meta-analysis of knee and hip osteoarthritis uncovers genetic differences between patients treated with joint replacement and patients without joint replacement.

OBJECTIVES: Osteoarthritis is a common and severe, multifactorial disease with a well-established genetic component. However, little is known about how genetics affect disease progression, and thereby the need for joint placement. Therefore, we aimed to investigate whether the genetic associations of knee and hip osteoarthritis differ between patients treated with joint replacement and patients without joint replacement. METHODS: We included knee and hip osteoarthritis cases along with healthy controls, altogether counting >700 000 individuals. The cases were divided into two groups based on joint replacement status (surgical vs non-surgical) and included in four genome-wide association meta-analyses: surgical knee osteoarthritis (N = 22 525), non-surgical knee osteoarthritis (N = 38 626), surgical hip osteoarthritis (N = 20 221) and non-surgical hip osteoarthritis (N = 17 847). In addition, we tested for genetic correlation between the osteoarthritis groups and the pain phenotypes intervertebral disc disorder, dorsalgia, fibromyalgia, migraine and joint pain. RESULTS: We identified 52 sequence variants associated with knee osteoarthritis (surgical: 17, non-surgical: 3) or hip osteoarthritis (surgical: 34, non-surgical: 1). For the surgical phenotypes, we identified 10 novel variants, including genes involved in autophagy (rs2447606 in ATG7) and mechanotransduction (rs202127176 in PIEZO1). One variant, rs13107325 in SLC39A8, associated more strongly with non-surgical knee osteoarthritis than surgical knee osteoarthritis. For all other variants, significance and effect sizes were higher for the surgical phenotypes. In contrast, genetic correlations with pain phenotypes tended to be stronger in the non-surgical groups. CONCLUSIONS: Our results indicate differences in genetic associations between knee and hip osteoarthritis depending on joint replacement status.

Weight-bearing cone-beam CT: the need for standardised acquisition protocols and measurements to fulfill high expectations-a review of the literature.

Weight bearing CT (WBCT) of the lower extremity is gaining momentum in evaluation of the foot/ankle and knee. A growing number of international studies use WBCT, which is promising for improving our understanding of anatomy and biomechanics during natural loading of the lower extremity. However, we believe there is risk of excessive enthusiasm for WBCT leading to premature application of the technique, before sufficiently robust protocols are in place e.g. standardised limb positioning and imaging planes, choice of anatomical landmarks and image slices used for individual measurements. Lack of standardisation could limit benefits from introducing WBCT in research and clinical practice because useful imaging information could become obscured. Measurements of bones and joints on WBCT are influenced by joint positioning and magnitude of loading, factors that need to be considered within a 3-D coordinate system. A proportion of WBCT studies examine inter- and intraobserver reproducibility for different radiological measurements in the knee or foot with reproducibility generally reported to be high. However, investigations of test-retest reproducibility are still lacking. Thus, the current ability to evaluate, e.g. the effects of surgery or structural disease progression, is questionable. This paper presents an overview of the relevant literature on WBCT in the lower extremity with an emphasis on factors that may affect measurement reproducibility in the foot/ankle and knee. We discuss the caveats of performing WBCT without consensus on imaging procedures and measurements.

Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): a cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis.

OBJECTIVE: Can ultrasound (US), MRI and X-ray applied to the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC) discriminate between patients with psoriatic arthritis (PsA), skin psoriasis (PsO) and hand osteoarthritis (OA)? METHODS: In this prospective, cross-sectional study, patients with DIP-joint PsA and nail involvement (n=50), PsO with nail involvement (n=12); and OA (n=13); were consecutively recruited. Risk ratios (RR) were calculated for US, MRI and X-ray findings of the DIP-joint and SEC between diagnoses. RESULTS: New bone formation (NBF) in US and MRI was a hallmark of OA, reducing the risk of having PsA (RR 0.52 (95% CI 0.43 to 0.63) and 0.64 (95% CI 0.56 to 0.74). The OA group was different from PsA and PsO on all MRI and X-ray outcomes reflected in a lower RR of having PsA; RR ranging from 0.20 (95% CI 0.13 to 0.31) for MRI bone marrow oedema (BMO) to 0.85 (95% CI 0.80 to 0.90) in X-ray enthesitis. No outcome in US, MRI or X-ray was significantly associated with a higher risk of PsA versus PsO, although there was a trend to a higher degree of US erosions and NBF in PsA. 82% of PsA and 67% of PsO was treated with disease modifying antirheumatic drugs which commonly reflects the clinical setting. CONCLUSION: High grade of US, MRI and X-ray NBF reduce the RR of having PsA compared with OA. In PsA versus PsO patients, there was a trend for US to demonstrate more structural changes in PsA although this did not reach significance.

Tapering of TNF inhibitors in axial spondyloarthritis in routine care - 2-year clinical and MRI outcomes and predictors of successful tapering.

OBJECTIVES: In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed. METHODS: One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression. RESULTS: One hundred and six patients (97%) completed 2 years' follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed. CONCLUSION: After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering.

Chronic Sequelae After Muscle Strain Injuries: Influence of Heavy Resistance Training on Functional and Structural Characteristics in a Randomized Controlled Trial.

BACKGROUND: Muscle strain injury leads to a high risk of recurrent injury in sports and can cause long-term symptoms such as weakness and pain. Scar tissue formation after strain injuries has been described, yet what ultrastructural changes might occur in the chronic phase of this injury have not. It is also unknown if persistent symptoms and morphological abnormalities of the tissue can be mitigated by strength training. PURPOSE: To investigate if heavy resistance training improves symptoms and structural abnormalities after strain injuries. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 30 participants with long-term weakness and/or pain after a strain injury of the thigh or calf muscles were randomized to eccentric heavy resistance training of the injured region or control exercises of the back and abdominal muscle. Isokinetic (hamstring) or isometric (calf) muscle strength was determined, muscle cross-sectional area measured, and pain and function evaluated. Scar tissue ultrastructure was determined from biopsy specimens taken from the injured area before and after the training intervention. RESULTS: Heavy resistance training over 3 months improved pain and function, normalized muscle strength deficits, and increased muscle cross-sectional area in the previously injured region. No systematic effect of training was found upon pathologic infiltration of fat and blood vessels into the previously injured area. Control exercises had no effect on strength, cross-sectional area, or scar tissue but a positive effect on patient-related outcome measures, such as pain and functional scores. CONCLUSION: Short-term strength training can improve sequelae symptoms and optimize muscle function even many years after a strain injury, but it does not seem to influence the overall structural abnormalities of the area with scar tissue. REGISTRATION: NCT02152098 (ClinicalTrials.gov identifier).

Quantifying the bone marrow composition of the healthy adult wrist with dual-energy CT.

PURPOSE: Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calcium (VNCa) values for absolute quantification of the bone marrow composition in the wrist. MATERIALS AND METHODS: We prospectively included consecutive adult participants and examined their wrists with DECT. Ranges of VNCa and calcium values were measured in the carpal bones, radius and ulna using a semi-automatic method. Bones with bone marrow edema, assessed by two blinded radiologists, were excluded. After determining optimum parameters for the three-material decomposition, the influence of calcium values, age and sex on VNCa values was assessed using multiple linear regression. RESULTS: 41 participants (Median age 53 years, range 20 years - 88 years, 51 % men) were enrolled and 399 bones assessed. At participant level mean VNCa values were -143 HU (SD 14 HU) using the current parameters for three-material decomposition and -104HU (SD 11 HU) with optimized parameters. There was a strong and significant influence of calcium values on VNCa values with the current parameters (p < 0.001, -0.137 HU[VNCa] / HU[Calcium]). With optimized parameters the calcium values and sex were not statistically significant predictors of VNCa values. Age was a significant, but clinically negligible, predictor (p = 0.03, -0.225 HU / year). CONCLUSIONS: After optimizing three-material decomposition parameters, calcium values, age and sex do not substantially influence virtual non-calcium values, and DECT may therefore be used for absolute quantification of the bone marrow composition - alleviating the need for reference bones or groups.

Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue.

Joint pain and osteoarthritis (OA) are some of the most common causes of lameness in horses, and most of the available treatments focus on symptomatic relief without a disease-modifying effect. TRPV1 is a potential target for treating joint diseases, including OA, and the present study aims to investigate if the TRPV1 receptor is present in equine articular tissue and determine whether the number of receptors is upregulated in joint inflammation. Metacarpo/metatarsophalangeal (MCP/MTP) joints from 15 horses euthanised for reasons unrelated to this study were included. Based on synovial fluid analysis, macroscopic evaluation, and magnetic resonance imaging (MRI), joints were divided into two groups: healthy joints and joints with pathology. ELISA analysis was performed on synovial tissue harvested from all joints. TPRV1 was found in all joints. The mean concentration of TRPV1 compared to total protein in healthy joints (8.4 × 10-7 ng/mL) and joints with pathology (12.9 × 10-7 ng/mL) differed significantly (p = 0.01, t-test with Welch correction). Quantitative real-time reverse transcriptase PCR analysis was performed on RNA isolates from synovial tissue from all joints. TRPV1 mRNA expression ratio normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in healthy joints (0.16 (SD: 0.19)) and joints with pathology (0.24 (SD: 0.14)) did not differ significantly (p = 0.43, t-test with Welch correction). mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-) was very low for both groups. In conclusion, TRPV1 was detected both on mRNA and the protein level, with a higher expression of TRPV1 in samples from joints with pathology. Future studies will determine the clinical potential of equine TRPV1 as a target in the management of joint pain and inflammation.

[Younger patients with hip joint pain].

This review summarises the present knowledge of diagnosing and treating hip joint pain. The results of joint preserving surgery are good in symptomatic patients with hip dysplasia, acetabular retroversion or impingement (cam or pincer) without signs of osteoarthritis. Confirmation of intraarticular pathology as the cause of symptoms is established clinically, and the pathology can in many cases be visualised by a standing, standardised radiograph of the pelvis, which is the basis for admission to the relevant orthopaedic department. We present an algorithm for this. Dysplasia and retroversion can be treated by periacetabular osteotomy and impingement by arthroscopic procedures.

Early development of tendinopathy in humans: Sequence of pathological changes in structure and tissue turnover signaling.

Overloading of tendon tissue with resulting chronic pain (tendinopathy) is a common disorder in occupational-, leisure- and sports-activity, but its pathogenesis remains poorly understood. To investigate the very early phase of tendinopathy, Achilles and patellar tendons were investigated in 200 physically active patients and 50 healthy control persons. Patients were divided into three groups: symptoms for 0-1 months (T1), 1-2 months (T2) or 2-3 months (T3). Tendinopathic Achilles tendon cross-sectional area determined by ultrasonography (US) was ~25% larger than in healthy control persons. Both Achilles and patellar anterior-posterior diameter were elevated in tendinopathy, and only later in Achilles was the width increased. Increased tendon size was accompanied by an increase in hypervascularization (US Doppler flow) without any change in mRNA for angiogenic factors. From patellar biopsies taken bilaterally, mRNA for most growth factors and tendon components remained unchanged (except for TGF-beta1 and substance-P) in early tendinopathy. Tendon stiffness remained unaltered over the first three months of tendinopathy and was similar to the asymptomatic contra-lateral tendon. In conclusion, this suggests that tendinopathy pathogenesis represents a disturbed tissue homeostasis with fluid accumulation. The disturbance is likely induced by repeated mechanical overloading rather than a partial rupture of the tendon.

Perfusion in bone marrow lesions assessed on DCE-MRI and its association with pain in knee osteoarthritis: a cross-sectional study.

OBJECTIVE: To investigate the association between pain and perfusion in bone marrow lesions with and without cysts assessed dynamic contrast-enhanced (DCE)-MRI in patients with knee osteoarthritis. SUBJECTS AND METHODS: In a cross-sectional setting, perfusion in bone marrow lesions was assessed using 3 Tesla MRI and correlated (Spearman's rank correlation) to pain using the knee injury and osteoarthritis outcome score (KOOS). Bone marrow lesions were assessed across the whole knee with DCE-MRI using heuristic variable and non-contrast-enhanced-MRI using MRI osteoarthritis knee score. RESULTS: Data were available from 107 participants. The participants had a mean age of 60.8 years, mean BMI of 34.5 kg/m2, mean KOOS-pain of 63.7 (0-100 scale), and mean bone marrow lesion sum score of 6.5 (0-45 scale). The bivariate association between KOOS-pain and the heuristic perfusion variable time to peak in bone marrow lesions containing subchondral cysts showed a statistically significant correlation (r = 0.40; p = 0.002). The perfusion variables were not correlated with KOOS-pain in bone marrow lesions without cysts. CONCLUSION: In this cross-sectional study, the rate of perfusion (TTP) in bone marrow lesions containing subchondral cysts was associated with pain in patients with knee OA. DCE-MRI has a potential to be used for separating subtypes of OA.

Optimising dual-energy CT scan parameters for virtual non-calcium imaging of the bone marrow: a phantom study.

BACKGROUND: We investigated the influence of dose, spectral separation, pitch, rotation time, and reconstruction kernel on accuracy and image noise of virtual non-calcium images using a bone marrow phantom. METHODS: The phantom was developed at our institution and scanned using a third-generation dual-source dual-energy CT scanner at five different spectral separations by varying the tube-voltage combinations (70 kV/Sn150 kV, 80 kV/Sn150 kV, 90 kV/Sn150 kV, and 100 kV/Sn150 kV, all with 0.6-mm tin filter [Sn]; 80 kV/140 kV without tin filter) at six different doses (volume computed tomography dose index from 1 to 80 mGy). In separate experiments, rotation times, pitch, and reconstruction kernels were varied at a constant dose and tube voltage. Accuracy was determined by measuring the mean error between virtual non-calcium values in the fluid within and outside of the bone. Image noise was defined as the standard deviation of virtual non-calcium values. RESULTS: Spectral separation, dose, rotation time, or pitch did not significantly correlate (p > 0.083) with mean error. Increased spectral separation (rs-0.96, p < 0.001) and increased dose (rs-0.98, p < 0.001) correlated significantly with decreased image noise. Increasing sharpness of the reconstruction kernel correlated with mean error (rs 0.83, p = 0.015) and image noise (rs 1.0, p < 0.001). CONCLUSIONS: Increased dose and increased spectral separation significantly lowered image noise in virtual non-calcium images but did not affect the accuracy. Virtual non-calcium reconstructions with similar accuracy and image noise could be achieved at a lower tube-voltage difference by increasing the dose.

Effect of Magnetic Resonance Imaging vs Conventional Treat-to-Target Strategies on Disease Activity Remission and Radiographic Progression in Rheumatoid Arthritis: The IMAGINE-RA Randomized Clinical Trial.

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown. Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission. Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017. Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission. Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life. Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events. Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA. Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study.

INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline. METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant. RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit. CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.