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.

Stable fixation of an ultra-short femoral neck-preserving hip prosthesis: a 5-year RSA, DXA, and clinical prospective outcome study of 48 patients.

BACKGROUND AND PURPOSE: We previously showed promising primary stability and preservation of bone stock with the ultra-short neck-loading hip implant in total hip arthroplasty (THA). The aim of this study was to evaluate clinical outcome, implant stability, and bone mineral density (BMD). METHODS: 50 patients were treated with the ultra-short neck Primoris hip implant at baseline and 48 were available for evaluation at 5-year follow-up. 5 different patient-reported outcome measures (PROMs) including hip-specific scores, disease-specific and generic quality of life outcome measures, and an activity score were used. Furthermore, implant stability using radiostereometric analysis (RSA) and assessment of periprosthetic BMD using dual-energy X-ray absorptiometry (DXA) were applied. RESULTS: By 1-year follow-up, all PROMs showed improvements and remained high at 5-year follow-up. After initial distal translation (subsidence) and negative rotation around the z-axis (varus tilt) the implant showed stable fixation at 5-year follow-up with no further migration beyond 12 months. In the regions of interest (ROI) 3 and 4, BMD remained stable. In ROI 2, further bone loss of 12% was found at 5-year follow-up. CONCLUSION: Clinical outcome including PROMs was satisfying throughout the 5-year follow-up period. The hip implant remains stable with both bone preservation and loss 5 years after surgery.

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.

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).

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.

Long-term ultrasound follow-up of intrathyroidal ectopic thymus in children.

OBJECTIVE: To present the sonographic follow-up of intrathyroidal ectopic thymus (IET) in children and adolescent patients. PATIENTS: Out of the 507 children referred to FNAB between 2006 and 2018, 30 (5.9%) pediatric patients (10 females), mean age 5.7 years (1.2-13.8, median 4.9 years) were diagnosed with IET. METHODS: A retrospective analysis of medical files of patients diagnosed with IET between 2006 and 2018. Assessed data included ultrasound characterisation, elastographic strain ratio (SR) results and hormonal evaluation. RESULTS: Analysis of thyroid US scans revealed that the mean age at the first thyroid ultrasound was 5.7 (1.2-13.8, median 4.9) years, and at the last US 10.7 (3.7-18, median 10.5) years. The mean time of the IET observation was 59.6 (2-148, median 53.5) months. On US, IET was hypoechoic with multiple linear and punctate echoes, hypovascular, fusiform on longitudinal plane and round or polygonal on an axial plane, more common in the right thyroid lobe (66.7%) and located in the posterior part of the lobes (54.5%), bilateral in two patients and multifocal in one patient. SR of IET was similar to the surrounding normal thyroid tissue. Complete regression of IET was observed in 12/30 patients after a mean time of 81.7 months (median 76.5), at the mean age of 13.7 (9.2-18, median 13.9) years. FNAB was performed in 10/30 and a hemithyroidectomy in 1/30 IET patients. In the FNAB (+) group, patients were younger (5.08 vs 6.08 years) and lesions were larger (0.12 ml vs 0.05 ml) than in the FNAB (-) group. All patients with IET were euthyroid with negative TPOAb and TgAb levels. CONCLUSION: The reproducibility of unique ultrasound features of IETs allows for safe long-term follow-up of these benign lesions in the majority of pediatric patients: not only monitoring the regression of IET but also screening towards the rare occurrence of a tumor arising from the IET.

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.

An Ultra-Short Femoral Neck-Preserving Hip Prosthesis: A 2-Year Follow-up Study with Radiostereometric Analysis and Dual X-Ray Absorptiometry in a Stepwise Introduction.

BACKGROUND: Total hip arthroplasty (THA) with a diaphyseal stem may risk bone loss. In order to save proximal bone stock in young patients with a high activity level and a long life expectancy, the interest in short stems has evolved. The purpose of this prospective observational cohort study was to evaluate the fixation of, and bone remodeling around, the Primoris femoral neck-preserving hip implant. METHODS: Fifty younger patients with end-stage osteoarthritis were managed with the Primoris hip implant. We evaluated bone mineral density (BMD) using dual x-ray absorptiometry (DXA) and implant migration using radiostereometric analysis (RSA). A region-of-interest (ROI) protocol for 4 ROIs was applied to assess BMD. The association between BMD and migration was evaluated to determine the fixation of the Primoris implant and bone remodeling in the proximal part of the femur. Follow-up evaluation was performed at regular intervals from day 1 (baseline) until 24 months after surgery. RESULTS: The major stem migrations were subsidence (Y axis; mean, 0.38 mm) at 6 weeks and varus tilt (rotation) (Z axis; mean, 0.93°) at 6 to 12 months. In ROI4 (the calcar area), a significant gain in bone was found with a mean difference of 4.1% (95% confidence interval [CI], 0.8% to 7.4%; p < 0.02) at 24 months postoperatively. Significant bone loss was found in ROI1 and ROI2, with a mean difference of -4.9% (95% CI, -7.4% to -2.4%; p = 0.0003) and -8.9% (95% CI, -11.5% to -6.2%; p = 0.0001), respectively. Linear regression and multivariate regression analysis showed a significant negative association between maximal total point motion and BMD (p = 0.02, R = 15%; and p < 0.05, R = 26%, respectively). CONCLUSIONS: The Primoris component showed satisfactory primary stability with promising results at the 24-month follow-up. DXA scans showed limited stress-shielding with the proximal loading pattern of the Primoris. Better bone quality was associated with less implant migration. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Follow-up of parenchymal changes in the thyroid gland with diffuse autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma.

PURPOSE: To present the outcomes of ultrasound (US) follow-ups in children with autoimmune thyroid disease who did not have a thyroid nodule on admission but developed papillary thyroid carcinoma (PTC) and to characterize the parenchymal changes in the thyroid gland prior to the development of PTC. METHODS: A retrospective thyroid US scan review of 327 patients diagnosed with AIT was performed. Forty patients (40/327, 12.2%) presented nodular AIT variant with a normoechogenic background. Eleven patients (11/327, 3.4%, 11/40, 27.5%) presenting this variant were diagnosed with PTC (nine females-mean age 15.3 years; two males aged 11 and 13 years). In five of 11 patients, the suspicious nodule that was later confirmed to be PTC was detected on the initial US at presentation. For the remaining six females (6/11) who developed PTC during the follow-up, we retrospectively analysed their US thyroid scans and these patients were selected for analysis in this study. RESULTS: On admission, the US evaluation revealed an enlarged normoechogenic thyroid gland in three patients and a hypoechogenic thyroid gland with fibrosis as indicated by irregular, chaotic hyperechogenic layers in three patients. No thyroid nodules were identified. Ultrasound monitoring revealed increasing echogenicity of the thyroid parenchyma during the follow-up. PTC developed in a mean time of 4.6 years (1 9/12-7 4/12 years) since referral to the outpatient thyroid clinic and 2.9 years (6/12-6 9/12) since the last nodule-free US thyroid scan. CONCLUSIONS: Sonographic follow-up assessments warrant further exploration as a strategy to determine PTC susceptibility in the paediatric population.

The association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other pain relevant brain structures-A 3-tesla MRI study of healthy men.

INTRODUCTION: Central sensitization plays a pivotal role in maintenance of pain and is believed to be intricately involved in several chronic pain conditions. One clinical manifestation of central sensitization is secondary hyperalgesia. The degree of secondary hyperalgesia presumably reflects individual levels of central sensitization. The objective of this study was to investigate the association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other brain structures involved in pain processing. MATERIALS AND METHODS: We recruited 121 healthy male participants; 118 were included in the final analysis. All participants underwent whole brain magnetic resonance imaging (MRI). Prior to MRI, all participants underwent pain testing. Secondary hyperalgesia was induced by brief thermal sensitization. Additionally, we recorded heat pain detection thresholds (HPDT), pain during one minute thermal stimulation (p-TS) and results of the Pain Catastrophizing Scale (PCS) and Hospital Anxiety and Depression score (HADS). RESULTS: We found no significant associations between the size of the area of secondary hyperalgesia and the volume of the caudate nuclei or of the following structures: primary somatosensory cortex, anterior and mid cingulate cortex, putamen, nucleus accumbens, globus pallidus, insula and the cerebellum. Likewise, we found no significant associations between the volume of the caudate nuclei and HPDTs, p-TS, PCS and HADS. CONCLUSIONS: Our findings indicate that the size of the secondary hyperalgesia area is not associated with the volume of brain structures relevant for pain processing, suggesting that the propensity to develop central sensitization, assessed as secondary hyperalgesia, is not correlated to brain structure volume.

Role of tissue perfusion, muscle strength recovery, and pain in rehabilitation after acute muscle strain injury: A randomized controlled trial comparing early and delayed rehabilitation.

Muscle strain injuries disrupt the muscle-tendon unit, early rehabilitation is associated with a faster return to sports (RTS), but the time course of tissue healing remains sparsely described. The purpose was to examine tissue regeneration and the effectiveness of early versus delayed rehabilitation onset on functional and structural recovery after strain injuries. A total of 50 recreational athletes with a severe acute strain injury in their thigh or calf muscles were randomized to early or delayed rehabilitation onset. Magnetic resonance imaging (MRI) was obtained initially, 3 and 6 months postinjury, and dynamic contrast-enhanced MRI (DCE-MRI) estimated tissue inflammation initially and after 6 months. Muscle strength was determined 5 weeks, 3 months, and 6 months postinjury, and a questionnaire determined soreness, pain, and confidence. DCE-MRI microvascular perfusion was higher in the injured compared to an uninjured muscle acutely (P < 0.01) and after 6 months (P < 0.01), for both groups (P > 0.05) and unrelated to RTS (P > 0.05). Total volume of the injured muscle decreased from the acute to the 3-month scan, and to the 6-month scan (P < 0.01) in both groups. Muscle strength was similar in both groups at any time. There was a nonsignificant trend (P ≤ 0.1) toward less pain and higher confidence with early rehabilitation. One reinjury was recorded. In conclusion, our data showed prolonged tissue repair with the initial response linked to muscle atrophy but did not explain why early rehabilitation onset accelerated recovery considering that structural and functional recovery was similar with early and delayed rehabilitation.

Bone remodelling of the proximal femur after total hip arthroplasty with 2 different hip implant designs: 15 years follow-up of the thrust plate prosthesis and the Bi-Metric stem.

INTRODUCTION: The thrust plate prosthesis (TPP) was introduced to preserve bone in patients undergoing total hip arthroplasty. We assessed the long-term results of hip arthroplasty in patients who received the TPP compared to a traditional intramedullary stem (Bi-Metric). METHODS: In this prospective observational cohort study, we evaluated bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), radiological imaging and clinical outcome using Harris Hip Score (HHS). Twenty patients received the TPP (group A) and 18 patients received the Bi-Metric stem (group B). Baseline was the 1st postoperative day, and subsequent follow-up was performed at 6 months, 1, 2, 8, 12 and 15 years after surgery. A four regions of interest (ROI) protocol was developed to assess BMD. RESULTS: In ROI1, bone resorption was significantly higher for group A at 6 months with a mean difference of 10% (95% confidence interval [CI], 4-16; p = 0.003) and 8% (95% CI, 1-15; p = 0.03) at 8 years. Regarding ROI4, group A had a lesser decrease in general compared to group B. The radiological findings did not reveal any subsidence or detectable implant migration. HHS improved from 53 (23-69) to 93 (55-100) in group A and from 51 (24-72) to 94 (78-100) in group B. CONCLUSION: The TPP was not found to be inferior to the Bi-Metric stem regarding bone preservation. The decrease in BMD in ROI4 was greater in group B. Clinical and radiological results also revealed that the TPP was not inferior to the Bi-Metric stem.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development.

BACKGROUND: The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3-43%. OBJECTIVE: To investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients. PATIENTS: 179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). METHODS: Retrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed. RESULTS: Analysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%-diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%-diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%-micronodulations and in 3.9%-diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background. CONCLUSION: Patients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

Point of no return for improvement of cartilage quality indicated by dGEMRIC before and after weight loss in patients with knee osteoarthritis: a cohort study.

Background It has been demonstrated that weight loss improves symptoms in obese subjects with knee osteoarthritis (KOA). A parallel change in cartilage morphology remains to be demonstrated. Purpose To demonstrate a parallel change in cartilage morphology. Material and Methods Obese patients with KOA were examined before and after weight loss over 16 weeks. Target knee joints were radiographically assessed by the Kellgren/Lawrence grading (KLG) system. Patients with KLG-1 and 2 changes in the lateral compartment were included. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was performed using intra-articular contrast. Results Nine patients with lateral KLG-1 and ten patients with lateral KLG-2 were studied. There were no group differences regarding the lateral compartment baseline dGEMRIC T1 values: median = 497 ms (KLG-1) and 533 ms (KLG-2) ( P = 0.12), or regarding reduction in body mass index (BMI) after 16 weeks: 12.8% versus 11.4% ( P = 0.74). In the KLG-1 group, several cases of increased dGEMRIC T1 values were seen and median value decreased significantly less than in KLG-2 group (15 ms versus 41 ms, P = 0.03) after weight loss. Conclusion Improvement of cartilage quality, assessed with dGEMRIC, after weight loss might be possible in early stage KOA (KLG-1), but not in later stage KOA (KLG-2). The results may suggest a point of no return for improvement of cartilage quality that should be tested in larger trials.

Navicular bone position determined by positional MRI: a reproducibility study.

OBJECTIVE: To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). MATERIALS AND METHODS: Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). RESULTS: Intraobserver and interobserver reliability was "substantial" in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was "moderate" for NVH (ICC 0.72) and "slight" for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). CONCLUSION: Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors.

Insulin resistance in adolescents with Turner syndrome is comparable to obese peers, but the overall metabolic risk is lower due to unknown mechanism.

PURPOSE: An increased risk of insulin resistance, hypertension and liver dysfunction is related to obesity (Ob), but may be also present in normal-weight Turner syndrome (TS) patients. The aim of the study was to compare metabolic risk in adolescents with TS and Ob. METHODS: The study included 21 non-obese with TS (all receiving human recombinant growth hormone, 17/21 estrogen/estrogen-progesterone), and 21 age-matched Ob girls (mean age 13.9 years). Glucose and serum insulin levels were assessed fasting and in 120' of standard oral glucose tolerance test. Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, alanine aminotransferase (ALT), FGF19, FGF21 and FGF23 levels were measured fasting. RESULTS: Mean BMI SDS was significantly lower in TS patients (0.1 vs 4.8 SD, p < 0.001). The mean systolic and diastolic blood pressure was significantly lower in TS patients (102.6 vs 124.2 mmHg, p < 0.001 and 67.1 vs 76.5 mmHg, p = 0.02). There were no differences concerning mean fasting, and post-load glucose (4.5 vs 4.3, 5.1 vs 5.8 mmol/L), and insulin (14.97 vs 17.19 and 69.3 vs 98.78 µIU/mL) levels, HOMA-IR (3.02 vs 3.4), TC (4.05 vs 4.4 mmol/L), TG (1.25 vs 1.37 mmol/L), ALT (26.9 vs 28.3 IU/L), FGF19 (232.8 vs 182.7 pg/mL), and FGF23 (12.3 vs 17.5 pg/mL) levels. Mean LDL (2.05 vs 2.7 mmol/L, p = 0.003) and FGF21 (293.9 vs 514.7 pg/mL, p = 0.007) levels were significantly lower, and HDL (1.7 vs 1.2 mmol/L, p < 0.001) level higher in TS group. CONCLUSIONS: Insulin resistance in adolescents with TS on growth hormone treatment is comparable to Ob patients, but overall metabolic risk factors seem to be lower.

Exercise-induced asthma in the competitive cold weather athlete.

Exercise-induced asthma (EIA) is a very common condition that affects winter sport athletes at rates as high as 50%. It has become clear that the main etiologic factors in EIA are the extremely low humidity and high respiratory rates in these athletes, which lead to extreme airway drying. New developments in objective testing for this condition have been recently described and are reviewed here. EIA is easily treated with oral and inhaled medications. These medications are closely regulated by the antidoping agencies; therefore, care must be taken by the treating physician to ensure compliance with the latest restrictions.