Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis ...and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.
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•Exercise reduces visceral adipose tissue mass•Loss of visceral adipose tissue mass following exercise is dependent on IL-6•IL-6 receptor blockade increases total cholesterol and is not influenced by exercise•Improvements in cardiorespiratory fitness following exercise are not IL-6 dependent
Wedell-Neergaard et al. show that in abdominally obese people, exercise-mediated loss of visceral adipose tissue mass requires IL-6 receptor signaling. Given that abdominal fat is metabolically harmful to health, this study raises a potentially important side effect of IL-6 receptor antibodies, such as tocilizumab, used to treat some forms of arthritis.
Movement artifacts compromise image quality and may interfere with interpretation, especially in magnetic resonance imaging (MRI) applications with low signal-to-noise ratio such as functional MRI or ...diffusion tensor imaging, and when imaging small lesions. High image resolution has high sensitivity to motion artifacts and often prolongs scan time that again aggravates movement artifacts. During the scan fast imaging techniques and sequences, optimal receiver coils, careful patient positioning, and instruction may minimize movement artifacts. Physiological noise sources are motion from respiration, flow and pulse coupled to cardiac cycles, from the swallowing reflex and small spontaneous head movements. Par example, in resting-state functional MRI spontaneous neuronal activity adds 1-2% of signal change, even under optimal conditions signal contributions from physiological noise remain a considerable fraction hereof. Movement tracking during imaging may allow for prospective correction or postprocessing steps separating signal and noise.
The UNet has become the golden standard method for the segmentation of 2D medical images that any new method must be validated against. In recent years, a number of variations to the seminal UNet ...have been proposed with promising results in the papers introducing them. However, there is no clear consensus if any of these architectures generalize as well and the UNet currently remains the methodological golden standard. For the segmentation of 3D scans, UNet‐inspired methods are also dominant, but there is a larger variety across applications. By evaluating the architectures in a different dimensionality, embedded in a different method, and for a different task, we aimed to evaluate if any of these UNet alternatives are promising as a new golden standard that generalizes even better than the UNet. The purpose of this study was to compare UNet inspired models for generalized 3D segmentation. To efficiently segment the 3D scans, we employed each UNet variant architecture as the central 2D segmentation core in the multi‐planar UNet 3D segmentation method that previously demonstrated excellent generalization in the MICCAI Segmentation Decathlon. It would strongly support a claim of generalizability, if a promising UNet‐variant consistently outperforms the UNet in this quite different setting. The experimental results show that the multi‐planar‐based UNet2+ (MPUNet2+) method outperforms other variants including the original multi‐planar UNet (MPUNet).
Background
Early cartilage changes in knee osteoarthritis (OA) can be assessed by both intravenous (i.v.) and intra‐articular (i.a.) delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC).
Purpose
To ...examine the relationship between i.a. dGEMRIC and delayed gadolinium‐enhanced MRI of menisci (dGEMRIM), and to investigate if the approach can be used to assess the morphological degeneration of menisci in obese patients with knee OA.
Study Type
Cross‐sectional.
Population
Eighty‐five obese patients with knee OA.
Field Strength/Sequences
1.5T. Inversion recovery sequence with four inversion times.
Assessment
T1 relaxation times were calculated for posterior weight‐bearing femoral cartilage and the posterior horns of the menisci. Meniscus degeneration sum score (0–2) was assessed as increased signal/no signal (1/0) and tear/no tear (1/0).
Statistical Tests
T1 relaxation times were compared using Student's t‐test. Comparison of cartilage and meniscus T1 relaxation times was done by regression analysis. Analysis of variance (ANOVA) was used for comparison of meniscal T1 relaxation times among the three summed morphological scores (0–2). Statistical analyses were performed with a level of significance at 0.05.
Results
For lateral menisci, morphology sum scores of 0, 1, and 2 were found in 13, 58, and 14 patients and for medial menisci in 2, 30, and 30 patients, respectively. Mean T1 relaxation times were 441 msec, 480 msec, and 497 msec for cartilage, lateral menisci, and medial menisci, respectively. T1 relaxation times for the menisci were similar (P = 0.53), and a weak correlation was found between dGEMRIC and dGEMRIM in the lateral compartments (R = 0.26). Comparing dGEMRIM between different morphology sum scores showed no differences (P > 0.4).
Data Conclusion
I.a. dGEMRIM showed no correlation between the degree of meniscal degeneration and meniscus T1 relaxation times. I.a. dGEMRIM do not seem to deliver useful information about meniscus degeneration to be suitable for clinical applications, but i.a. dGEMRIC may still be considered an alternative contrast‐saving method for cartilage.
Level of Evidence: 3
Technical Efficacy: Stage 3
J. Magn. Reson. Imaging 2018;48:1700–1706
•Exercise therapy reduced pain compared with controls in knee osteoarthritis.•Inflammatory activity was unchanged in the exercise group compared with controls.•Reduction in pain was not explained by ...changes in inflammatory activity.•The results suggest that exercise is not harmful in knee osteoarthritis.
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.
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.
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.
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.
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.
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.
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.
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.
Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors ...influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive. Injury-induced secondary hyperalgesia can be elicited by experimental pain models in humans, and is believed to be a result of central sensitization. Secondary hyperalgesia may thus reflect the individual level of central sensitization. The objective of this study was to investigate possible associations between increasing size of secondary hyperalgesia area and brain connectivity in known resting-state networks. We recruited 121 healthy participants (male, age 22, SD 3.35) who underwent resting-state functional magnetic resonance imaging. Prior to the scan session, areas of secondary hyperalgesia following brief thermal sensitization (3 min. 45 °C heat stimulation) were evaluated in all participants. 115 participants were included in the final analysis. We found a positive correlation (increasing connectivity) with increasing area of secondary hyperalgesia in the sensorimotor- and default mode networks. We also observed a negative correlation (decreasing connectivity) with increasing secondary hyperalgesia area in the sensorimotor-, fronto-parietal-, and default mode networks. Our findings indicate that increasing area of secondary hyperalgesia is associated with increasing and decreasing connectivity in multiple networks, suggesting that differences in the propensity for central sensitization, assessed as secondary hyperalgesia areas, may be expressed as differences in the resting-state central neuronal activity.
Exercise therapy is recommended for knee osteoarthritis (OA), but the underlying mechanisms of pain relief are not fully understood. The purpose of this study was to explore the effects of exercise ...on muscle perfusion assessed by dynamic contrast enhanced MRI (DCE-MRI) and its association with changes in pain in patients with knee OA.
Exploratory outcome analyses of a randomised controlled study with per-protocol analyses ( ClinicalTrials.gov : NCT01545258) performed at an outpatient clinic at a public hospital in Denmark. We compared 12 weeks of supervised exercise therapy 3 times per week (ET) with a no attention control group (CG). Analyses of covariance (ANCOVA) were used to assess group mean differences in changes from baseline to week 12 in knee muscle perfusion quantified by DCE-MRI, patient-reported pain and function using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, knee extensor and flexor muscle strength tests, and the six-minute walking test (6MWT). Spearman's correlation coefficients were used to determine the correlation between changes in DCE-MRI variables, KOOS, muscle strength, and 6MWT. The potential effect mediation of the DCE-MRI perfusion variables was investigated in a post-hoc mediation analysis.
Of 60 participants randomised with knee osteoarthritis, 33 (ET, n = 16, CG, n = 17) adhered to the protocol and had complete DCE-MRI data. At follow-up, there were significant group differences in muscle perfusion changes and clinically relevant group differences in KOOS pain changes (10.7, 95% CI 3.3 to 18.1, P = 0.006) in favor of ET. There were no significant between-group differences on muscle strength and function. The changes in pain and muscle perfusion were significantly correlated (highest Spearman's rho = 0.42, P = 0.014). The mediation analyses were generally not statistically significant.
The pain-reducing effects of a 12-week exercise program are associated with changes in knee muscle perfusion quantified by DCE-MRI in individuals with knee OA, but whether the effects are mediated by muscle perfusion changes remains unclear.
ClinicalTrials.gov: NCT01545258 , first posted March 6, 2012.
ObjectivesTo find determining factors for persistent infarction signs in patients with transient ischaemic attack (TIA), herein initial diffusion lesion size, visibility on apparent diffusion ...coefficient (ADC) or fluid-attenuated inversion recovery (FLAIR) and location.DesignProspective cohort study of patients with clinical TIA receiving 3T-MRI within 72 hours of symptom onset and at 8-week follow-up.SettingClinical workflow in a single tertiary stroke centre between February 2012 and June 2014.Participants199 candidate patients were recruited, 64 patients were excluded due to non-TIA discharge diagnosis or no 8-week MRI. 122 patients completed the study.Primary outcome measuresThe primary outcome was visible persistent infarction defined as 8-week FLAIR hyperintensity or atrophy corresponding to the initial diffusion-weighted imaging (DWI) lesion.Results50 patients showed 84 initial DWI lesions. 29 (35%) DWI lesions did not result in infarction signs on 8-week FLAIR. 26 (90%, P<0.0001) reversing lesions were located in the cortical grey matter (cGM). cGM location (vs any other location) strongly predicted no 8-week infarction sign development (OR 0.02, 95% CI 0.001 to 0.17) or partial lesion area decrease (>30% of initial DWI-area, OR 14.10, 95% CI 3.61 to 54.72), adjusted for FLAIR-visibility, DWI-area, ADC-confirmation and time to scan (TTS) from symptom onset to baseline MRI. Acute FLAIR-visibility was a strong associated factor for persistent infarction signs (OR 33.06, 95% CI 2.94 to 1432.34). For cGM lesions area size was sole associated factor for persistent infarction signs with a 0.31 cm2 (area under the curve (AUC), 0.97) threshold. In eight (16%) DWI-positive patients, all lesions reversed fully.Conclusions16% of DWI-positive patients and one-third of acute DWI lesions caused no persistent infarction signs, especially small cGM lesions were not followed by development of persistent infarction signs. Late MRI after TIA is likely to be less useful in the clinical setting, and it is dubious if the absence of old vascular lesions can be taken as evidence of no prior ischaemic attacks.Trial registration number NCT01531946; Results.
Contrast-enhanced MR imaging (CE-MR imaging) is recommended for diagnosis and monitoring of infectious and most inflammatory joint diseases. CE-MR imaging clearly differentiates soft and bony tissue ...from fluid collections and infectious debris. To improve imaging information, a dynamic CE-MR imaging sequence (DCE-MR imaging) sequence can be applied using fast T1-weighted sequential image acquisition during contrast injection. Use of DCE-MR imaging allows robust extraction of quantitative information regarding blood flow and capillary permeability, especially when dedicated analysis methods and software are used to analyze contrast kinetics. This article describes principles of DCE-MR imaging for the assessment of infectious and inflammatory joint diseases.
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