Glucagon resistance in individuals with obesity and hepatic steatosis can be measured using the GLUSENTIC test and index.

Increased plasma levels of glucagon (hyperglucagonaemia) promote diabetes development but is also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance towards amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, consisting of two study days: a glucagon injection and measurements of plasma amino acids, and an infusion of mixed amino acids and subsequent calculation of the GLUSENTIC index (primary outcome measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The delta-decline in total amino acids was 49% lower in MASLD following exogenous glucagon (p=0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (p<0.0001), but not T1D (p>0.99). In contrast, glucagon-induced glucose increments were similar in controls and MASLD (p=0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD.

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.

Glucagon augments the secretion of FGF21 and GDF15 in MASLD by indirect mechanisms.

INTRODUCTION: Glucagon receptor agonism is currently explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The metabolic effects of glucagon receptor agonism may in part be mediated by increases in circulating levels of Fibroblast Growth Factor 21 (FGF21) and Growth Differentiation Factor 15 (GDF15). The effect of glucagon agonism on FGF21 and GDF15 levels remains uncertain, especially in the context of elevated insulin levels commonly observed in metabolic diseases. METHODS: We investigated the effect of a single bolus of glucagon and a continuous infusion of glucagon on plasma concentrations of FGF21 and GDF15 in conditions of endogenous low or high insulin levels. The studies included individuals with overweight with and without MASLD, healthy controls (CON) and individuals with type 1 diabetes (T1D). The direct effect of glucagon on FGF21 and GDF15 was evaluated using our in-house developed isolated perfused mouse liver model. RESULTS: FGF21 and GDF15 correlated with plasma levels of insulin, but not glucagon, and their secretion was highly increased in MASLD compared with CON and T1D. Furthermore, FGF21 levels in individuals with overweight with or without MASLD did not increase after glucagon stimulation when insulin levels were kept constant. FGF21 and GDF15 levels were unaffected by direct stimulation with glucagon in the isolated perfused mouse liver. CONCLUSION: The glucagon-induced secretion of FGF21 and GDF15 is augmented in MASLD and may depend on insulin. Thus, glucagon receptor agonism may augment its metabolic benefits in patients with MASLD through enhanced secretion of FGF21 and GDF15.

Change in abdominal obesity after colon cancer surgery - effects of left-sided and right-sided colonic resection.

BACKGROUND: Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots. MATERIAL AND METHODS: Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately. RESULTS: A total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2-9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2-6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2-7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4-9%, p < 0.001) increase in SAT and a 4% (95% CI: 1-7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2-10%, p < 0.01) after 3 years. CONCLUSION: After 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT.

Constructing a clinical radiographic knee osteoarthritis database using artificial intelligence tools with limited human labor: A proof of principle.

OBJECTIVE: To create a scalable and feasible retrospective consecutive knee osteoarthritis (OA) radiographic database with limited human labor using commercial and custom-built artificial intelligence (AI) tools. METHODS: We applied four AI tools, two commercially available and two custom-built tools, to analyze 6 years of clinical consecutive knee radiographs from patients aged 35-79 at the University of Copenhagen Hospital, Bispebjerg-Frederiksberg Hospital, Denmark. The tools provided Kellgren-Lawrence (KL) grades, joint space widths, patella osteophyte detection, radiographic view detection, knee joint implant detection, and radiographic marker detection. RESULTS: In total, 25,778 knee radiographs from 8575 patients were included in the database after excluding inapplicable radiographs, and 92.5% of the knees had a complete OA dataset. Using the four AI tools, we saved about 800 hours of radiologist reading time and only manually reviewed 16.0% of the images in the database. CONCLUSIONS: This study shows that clinical knee OA databases can be built using AI with limited human reading time for uniform grading and measurements. The concept is scalable temporally and across geographic regions and could help diversify further OA research by efficiently including radiographic knee OA data from different populations globally. We can prevent data dredging and overfitting OA theories on existing trite cohorts by including various gene pools and continuous expansion of new clinical cohorts. Furthermore, the suggested tools and applied approaches provide an ability to retest previous hypotheses and test new hypotheses on real-life clinical data with current disease prevalence and trends.

Should artificial intelligence have lower acceptable error rates than humans?

The first patient was misclassified in the diagnostic conclusion according to a local clinical expert opinion in a new clinical implementation of a knee osteoarthritis artificial intelligence (AI) algorithm at Bispebjerg-Frederiksberg University Hospital, Copenhagen, Denmark. In preparation for the evaluation of the AI algorithm, the implementation team collaborated with internal and external partners to plan workflows, and the algorithm was externally validated. After the misclassification, the team was left wondering: what is an acceptable error rate for a low-risk AI diagnostic algorithm? A survey among employees at the Department of Radiology showed significantly lower acceptable error rates for AI (6.8 %) than humans (11.3 %). A general mistrust of AI could cause the discrepancy in acceptable errors. AI may have the disadvantage of limited social capital and likeability compared to human co-workers, and therefore, less potential for forgiveness. Future AI development and implementation require further investigation of the fear of AI's unknown errors to enhance the trustworthiness of perceiving AI as a co-worker. Benchmark tools, transparency, and explainability are also needed to evaluate AI algorithms in clinical implementations to ensure acceptable performance.

Reliability and correlation of weight-bearing cone beam CT and Foot Posture Index (FPI) for measurements of foot posture: a test-retest study.

OBJECTIVE: To assess test-retest reliability and correlation of weight-bearing (WB) and non-weight-bearing (NWB) cone beam CT (CBCT) foot measurements and Foot Posture Index (FPI) MATERIALS AND METHODS: Twenty healthy participants (age 43.11±11.36, 15 males, 5 females) were CBCT-scanned in February 2019 on two separate days on one foot in both WB and NWB positions. Three radiology observers measured the navicular bone position. Plantar (ΔNAVplantar) and medial navicular displacements (ΔNAVmedial) were calculated as a measure of foot posture changes under loading. FPI was assessed by two rheumatologists on the same two days. FPI is a clinical measurement of foot posture with 3 rearfoot and 3 midfoot/forefoot scores. Test-retest reproducibility was determined for all measurements. CBCT was correlated to FPI total and subscores. RESULTS: Intra- and interobserver reliabilities for navicular position and FPI were excellent (intraclass correlation coefficient (ICC) .875-.997). In particular, intraobserver (ICC .0.967-1.000) and interobserver reliabilities (ICC .946-.997) were found for CBCT navicular height and medial position. Interobserver reliability of ΔNAVplantar was excellent (ICC .926 (.812; .971); MDC 2.22), whereas the ΔNAVmedial was fair-good (ICC .452 (.385; .783); MDC 2.42 mm). Using all observers' measurements, we could calculate mean ΔNAVplantar (4.25±2.08 mm) and ΔNAVmedial (1.55±0.83 mm). We demonstrated a small day-day difference in ΔNAVplantar (0.64 ±1.13mm; p<.05), but not for ΔNAVmedial (0.04 ±1.13mm; p=n.s.). Correlation of WBCT (WB navicular height - ΔNAVmedial) with total clinical FPI scores and FPI subscores, respectively, showed high correlation (ρ: -.706; ρ: -.721). CONCLUSION: CBCT and FPI are reliable measurements of foot posture, with a high correlation between the two measurements.

The Effect of Endoscopic Partial Plantar Fasciotomy on Morphologic and Functional Properties of the Foot.

BACKGROUND: The lifetime risk of plantar fasciitis is 10%, and operative treatment in the form of endoscopic partial plantar fascia release are often performed in cases refractory for nonsurgical treatment. The effect of the operation on the biomechanical properties of the foot has only been sparsely studied. METHODS: This is a prospective, observational study of 25 patients with plantar fasciitis, for a minimum of 3 months, verified by ultrasonographic scanning, who had endoscopic partial fasciotomy. A bony spur was resected if present. At the calcaneal insertion, the medial half of the central band of the plantar fascia was excised in full thickness. The biomechanical properties of the foot were evaluated before surgery and 12 months postoperatively. RESULTS: Foot length increased 0.17 cm (P = .03), the width of the central zone 0.35 cm (P = .019), the modified arch index 0.05 (P = .032), and the Foot Posture Index 1.0 (P = .0014). There were no significant changes in rearfoot eversion angle, ankle dorsiflexion and jump distance, or in magnetic resonance imaging-measured 3D navicular position from pre- to postoperation, with or without loading, and no changes in ultrasonographically measured heel pad thickness. A tantalum bead (0.7-mm-diameter) was inserted during operation into the most proximal part of the released medial plantar fascia. Radiographs obtained few days postoperatively and 1 year later revealed no changes in the tantalum-calcaneus distance in supine position, but an increase from 48.3 to 50.7 mm (P = .045) in one-leg standing, suggesting a higher flexibility of the remaining fascia. Patients with a body mass index above and below 27.0 demonstrated no significant differences in any of the assessments at 12 months. CONCLUSION: There were minimal changes in the measured foot morphologic and functional properties at 1-year follow-up, after endoscopic partial plantar fascia release. LEVEL OF EVIDENCE: Level II, prospective cohort study.

Autonomous Chest Radiograph Reporting Using AI: Estimation of Clinical Impact.

Background Automated interpretation of normal chest radiographs could alleviate the workload of radiologists. However, the performance of such an artificial intelligence (AI) tool compared with clinical radiology reports has not been established. Purpose To perform an external evaluation of a commercially available AI tool for (a) the number of chest radiographs autonomously reported, (b) the sensitivity for AI detection of abnormal chest radiographs, and (c) the performance of AI compared with that of the clinical radiology reports. Materials and Methods In this retrospective study, consecutive posteroanterior chest radiographs from adult patients in four hospitals in the capital region of Denmark were obtained in January 2020, including images from emergency department patients, in-hospital patients, and outpatients. Three thoracic radiologists labeled chest radiographs in a reference standard based on chest radiograph findings into the following categories: critical, other remarkable, unremarkable, or normal (no abnormalities). AI classified chest radiographs as high confidence normal (normal) or not high confidence normal (abnormal). Results A total of 1529 patients were included for analysis (median age, 69 years [IQR, 55-69 years]; 776 women), with 1100 (72%) classified by the reference standard as having abnormal radiographs, 617 (40%) as having critical abnormal radiographs, and 429 (28%) as having normal radiographs. For comparison, clinical radiology reports were classified based on the text and insufficient reports excluded (n = 22). The sensitivity of AI was 99.1% (95% CI: 98.3, 99.6; 1090 of 1100 patients) for abnormal radiographs and 99.8% (95% CI: 99.1, 99.9; 616 of 617 patients) for critical radiographs. Corresponding sensitivities for radiologist reports were 72.3% (95% CI: 69.5, 74.9; 779 of 1078 patients) and 93.5% (95% CI: 91.2, 95.3; 558 of 597 patients), respectively. Specificity of AI, and hence the potential autonomous reporting rate, was 28.0% of all normal posteroanterior chest radiographs (95% CI: 23.8, 32.5; 120 of 429 patients), or 7.8% (120 of 1529 patients) of all posteroanterior chest radiographs. Conclusion Of all normal posteroanterior chest radiographs, 28% were autonomously reported by AI with a sensitivity for any abnormalities higher than 99%. This corresponded to 7.8% of the entire posteroanterior chest radiograph production. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Park in this issue.

Development of a glucagon sensitivity test in humans: Pilot data and the GLUSENTIC study protocol.

A physiological feedback system exists between hepatocytes and the alpha cells, termed the liver-alpha cell axis and refers to the relationship between amino acid-stimulated glucagon secretion and glucagon-stimulated amino acid catabolism. Several reports indicate that non-alcoholic fatty liver disease (NAFLD) disrupts the liver-alpha cell axis, because of impaired glucagon receptor signaling (glucagon resistance). However, no experimental test exists to assess glucagon resistance in humans. The objective was to develop an experimental test to determine glucagon sensitivity with respect to amino acid and glucose metabolism in humans. The proposed glucagon sensitivity test (comprising two elements: 1) i.v. injection of 0.2 mg glucagon and 2) infusion of mixed amino acids 331 mg/hour/kg) is based on nine pilot studies which are presented. Calculation of a proposed glucagon sensitivity index with respect to amino acid catabolism is also described. Secondly, we describe a complete study protocol (GLUSENTIC) according to which the glucagon sensitivity test will be applied in a cross-sectional study currently taking place. 65 participants including 20 individuals with a BMI 18.6-25 kg/m2, 30 individuals with a BMI ≥ 25-40 kg/m2, and 15 individuals with type 1 diabetes with a BMI between 18.6 and 40 kg/m2 will be included. Participants will be grouped according to their degree of hepatic steatosis measured by whole-liver magnetic resonance imaging (MRI). The primary outcome measure will be differences in the glucagon sensitivity index between individuals with and without hepatic steatosis. Developing a glucagon sensitivity test and index may provide insight into the physiological and pathophysiological mechanism of glucagon action and glucagon-based therapies.

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.

External validation of an artificial intelligence tool for radiographic knee osteoarthritis severity classification.

PURPOSE: To externally validate an artificial intelligence (AI) tool for radiographic knee osteoarthritis severity classification on a clinical dataset. METHOD: This retrospective, consecutive patient sample, external validation study used weight-bearing, non-fixed-flexion posterior-anterior knee radiographs from a clinical production PACS. The index test was ordinal Kellgren-Lawrence grading by an AI tool, two musculoskeletal radiology consultants, two reporting technologists, and two resident radiologists. Grading was repeated by all readers after at least four weeks. Reference test was the consensus of the two consultants. The primary outcome was quadratic weighted kappa. Secondary outcomes were ordinal weighted accuracy, multiclass accuracy and F1-score. RESULTS: 50 consecutive patients between September 24, 2019 and October 22, 2019 were retrospectively included (3 excluded) totaling 99 knees (1 excluded). Quadratic weighted kappa for the AI tool and the consultant consensus was 0.88 CI95% (0.82-0.92). Agreement between the consultants was 0.89 CI95% (0.85-0.93). Intra-rater agreements for the consultants were 0.96 CI95% (0.94-0.98) and 0.94 CI95% (0.91-0.96) respectively. For the AI tool it was 1 CI95% (1-1). For the AI tool, ordinal weighted accuracy was 97.8% CI95% (96.9-98.6 %). Average multiclass accuracy and F1-score were 84% (83/99) CI95% (77-91%) and 0.67 CI95% (0.51-0.81). CONCLUSIONS: The AI tool achieved the same good-to-excellent agreement with the radiology consultant consensus for radiographic knee osteoarthritis severity classification as the consultants did with each other.

Habitual side-specific loading leads to structural, mechanical, and compositional changes in the patellar tendon of young and senior lifelong male athletes.

Effects of lifelong physical activity on tendon function have been investigated in cross-sectional studies, but these are at risk of "survivorship" bias. Here, we investigate whether lifelong side-specific loading is associated with greater cross-sectional area (CSA), mechanical properties, cell density (DNA content), and collagen cross-link composition of the male human patellar tendon (PT), in vivo. Nine seniors and six young male lifelong elite badminton players and fencers were included. CSA of the PT obtained by 3-tesla MRI and ultrasonography-based bilateral PT mechanics were assessed. Collagen fibril characteristics, enzymatic cross links, nonenzymatic glycation (autofluorescence), collagen, and DNA content were measured biochemically in PT biopsies. The elite athletes had a ≥15% side-to-side difference in maximal knee extensor strength, reflecting chronic unilateral sport-specific loading patterns. The PT CSA was greater on the lead extremity compared with the nonlead extremity (17%, P = 0.0001). Furthermore, greater tendon stiffness (18%, P = 0.0404) together with lower tendon stress (22%, P = 0.0005) and tendon strain (18%, P = 0.0433) were observed on the lead extremity. No effects were demonstrated from side-to-side for glycation, enzymatic cross link, collagen, and DNA content (50%, P = 0.1160). Moreover, tendon fibril density was 87 ± 28 fibrils/µm2 on the lead extremity and 68 ± 26 fibrils/µm2 on the nonlead extremity (28%, P = 0.0544). Tendon fibril diameter was 86 ± 14 nm on the lead extremity and 94 ± 14 nm on the nonlead extremity (-9%, P = 0.1076). These novel data suggest that lifelong side-specific loading in males yields greater patellar tendon size and stiffness possibly with concomitant greater fibril density but without changes of collagen cross-link composition.NEW & NOTEWORTHY The present data demonstrate that lifelong side-specific loading yields greater patellar tendon structure on the lead extremity without affecting glycation that is associated with aging. These novel data suggest that lifelong side-specific habitual loading induce structural alterations that may serve to improve the mechanical properties of the tendon.

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).

Magnetic Resonance T2 * Is Increased in Patients With Early-Stage Achilles and Patellar Tendinopathy.

BACKGROUND: T2 * mapping has proven useful in tendon research and may have the ability to detect subtle changes at an early stage of tendinopathy. PURPOSE: To investigate the difference in T2 * between patients with early tendinopathy and healthy controls, and to investigate the relationship between T2 * and clinical outcomes, tendon size, and mechanical properties. STUDY TYPE: Prospective cross-sectional. SUBJECTS: Sixty-five patients with early tendinopathy and 25 healthy controls. FIELD STRENGTH/SEQUENCE: Three Tesla, ultrashort time to echo magnetic resonance imaging. ASSESSMENT: Tendon T2 * was quantified using a monoexponential fitting algorithm. Clinical symptoms were evaluated using the Victorian Institute of Sports Assessment-Achilles/Patella (VISA-A/VISA-P). In vivo mechanical properties were measured using an ultrasound-based method that determined force and deformation simultaneously in tendons of patellar tendinopathy patients. STATISTICAL TESTS: A generalized linear model adjusted for age was applied to investigate the difference between patients and controls. In the two patient groups, linear regressions were applied to investigate the association between T2 * and tendon size, clinical outcomes, and biomechanical properties. RESULTS: There was a significant difference in T2 * between patients and healthy controls (204.8 [95% CI: 44.5-365.0] µsec, P < 0.05). There was a positive correlation between tendon size and T2 * for both Achilles (r = 0.72; P < 0.05) and patellar tendons (r = 0.53; P < 0.05). There was no significant correlation between VISA-A and T2 * (r = -0.2; P = 0.17) or VISA-P and T2 * (r = -0.5; P = 0.0504). Lastly, there was a negative correlation between modulus and T2 * (r = -0.51; P < 0.05). DATA CONCLUSIONS: T2 * mapping can detect subtle structural changes that translate to altered mechanical properties in early-phase tendinopathy. However, T2 * did not correlate with clinical scores in patients with early-phase Achilles and patellar tendinopathy. Thus, T2 * mapping may serve as a tool for early detection of structural changes in tendinopathy but does not necessarily describe the clinical severity of disease. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

No Additive Clinical or Physiological Effects of Short-term Anti-inflammatory Treatment to Physical Rehabilitation in the Early Phase of Human Achilles Tendinopathy: A Randomized Controlled Trial.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of Achilles tendinopathy, but whether they have any additive clinical effect on physical rehabilitation in the early phase of tendinopathy remains unknown. PURPOSE/HYPOTHESIS: To investigate whether an initial short-term NSAID treatment added to a physical rehabilitation program in the early phase of Achilles tendinopathy would have an additive effect. We hypothesized that the combination of NSAID and rehabilitation would be superior to rehabilitation alone. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 69 patients with early phase Achilles tendinopathy (lasting <3 months) were randomly assigned to either a naproxen group (7 days of treatment; 500 mg twice daily; n = 34) or a placebo group (7 days of placebo treatment; n = 35). Both groups received an identical 12-week physical rehabilitation program. The clinical outcome of the study was evaluated using the Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire and a numerical rating scale (NRS), and the physiological outcome was evaluated using ultrasonography, magnetic resonance imaging (MRI), and ultra-short time to echo T2* mapping MRI (UTE T2* MRI). Follow-up was performed at 1 week, 3 months, and 1 year. Time effects are presented as mean difference ± SEM. RESULTS: No significant differences were found between the 2 treatment groups for any of the outcome measures at any time point (P > .05). For the VISA-A score, a significant time effect was observed between baseline and 3-month follow-up (14.9 ± 2.3; P < .0001), and at 1-year follow-up, additional improvements were observed (6.1 ± 2.3; P < .01). Furthermore, the change in VISA-A score between baseline and 3-month follow-up was greater in patients with very short symptom duration (<1 month) at baseline compared with patients who had longer symptom duration (>2 months) (interaction between groups, 11.7 ± 4.2; P < .01). Despite clinical improvements, total weekly physical activity remained lower compared with preinjury levels at 3 months (-2.7 ± 0.5 h/wk; P < .0001) and 1 year (-3.0 ± 0.5 h/wk; P < .0001). At baseline, ultrasonography showed increased thickness (0.12 ± 0.03 cm; P < .0001) and vascularity (0.3 ± 0.1 cm2; P < .005) on the tendinopathic side compared with the contralateral side, but no changes over time were observed for ultrasonography, MRI, or UTE T2* MRI results. CONCLUSION: Clinical symptoms in early tendinopathy improved with physical rehabilitation, but this improvement was not augmented with the addition of NSAID treatment. Furthermore, this clinical recovery occurred in the absence of any measurable structural alterations. Finally, clinical improvements after a physical rehabilitation program were greater in patients with very short symptom duration compared with patients who had longer symptom duration. REGISTRATION: NCT03401177 (ClinicalTrials.gov identifier) and BFH-2016-019 (Danish Data Protection Agency).

The effect of exercise therapy on inflammatory activity assessed by MRI in knee osteoarthritis: Secondary outcomes from a randomized controlled trial.

OBJECTIVE: This study investigated the effect of exercise therapy on inflammatory activity in synovitis and bone marrow lesions (BMLs) assessed by magnetic resonance imaging (MRI) in patients with knee OA. METHODS: 60 patients with knee OA were randomized 1:1 to 12 weeks of supervised exercise therapy 3 times/week (ET) or a no-attention control group (CG). Synovitis and BMLs were assessed with static MRI with and without contrast and with dynamic contrast enhanced MRI (DCE-MRI). DCE-MRI data was quantified using pixel-by-pixel methodology based on analysis of signal intensity curves. Pain was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses of covariance were used assessing group differences in changes from baseline to week 12. RESULTS: 33 patients adhered to the protocol and had valid MRI and KOOS data (ET, n = 16, CG, n = 17). Statistically significant and clinically relevant group difference in favour of ET was seen in KOOS pain change (-11.7 points, 95%CI: -20.1 to -3.4). There were statistically significant group differences in DCE-MRI assessed synovitis in the anterior synovium with unchanged inflammatory activity in the ET group compared to the CG. There were no group differences in BMLs and static MRI. CONCLUSION: Inflammatory activity was unchanged, and pain was reduced in patients with knee OA adhering to 12 weeks of exercise therapy compared to a no-attention control group. The reduction in pain was not explained by changes in inflammatory activity. Overall, the results suggest that exercise is not harmful in knee OA. ClinicalTrials.gov number: NCT01545258.

UTE T2* mapping of tendinopathic patellar tendons: an MRI reproducibility study.

BACKGROUND: There is currently a lack of imaging modalities that can be used as a sensitive measure in tendinopathy. Recent findings suggest the applicability of ultra-short echo time (UTE) magnetic resonance imaging (MRI) T2* mapping in tendons, but the reproducibility remains unknown. PURPOSE: To evaluate test-retest reproducibility of UTE MRI T2* mapping of tendinopathic patellar tendons and to evaluate the intra- and inter-observer reproducibility of the measurement. MATERIAL AND METHODS: Fifteen patients with chronic patellar tendinopathy were evaluated with UTE MRI twice in a 3.0-T scanner on the same day. Manual segmentation of the patellar tendon was performed by two blinded investigators and automated T2*map reconstruction was performed in custom-made software. RESULTS: There was a significant and numerically small difference in test-retest T2* values (T2*meandiff = 0.06 ± 0.07 ms ≈ 3.7%; P = 0.006) with an ICC = 0.91 (95% confidence interval [CI] 0.58-0.98; typical error of 3.0%). The intra- and inter-observer reproducibility showed no significant bias (P = 0.493 and P = 0.052), and generally substantial reproducibility was demonstrated for T2* (intra-observer ICC = 0.99; 95% CI 0.98-1.00 and inter-observer ICC = 0.99; 95% CI 0.96-1.00, and typical error 1.3% and 1.3%, respectively). CONCLUSION: These data demonstrate a small bias between repeated measurements for UTE T2*, but with a very low associated mean difference (3.7%) between the two tests. The high ICC values and low typical error % demonstrate reproducibility of repeated T2*-mapping sessions. Further, the method showed substantial intra- and inter-observer reproducibility for T2* values proving feasibility for use of UTE T2* mapping in research and clinical practice.