Intramuscular Fatty Infiltration Research Articles

Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration in older adults: relevance for clinical practice and research.

(1) To compare older adults stratified by supraspinatus tendon tear status (STT status)-no tear (Intact), partial-thickness (PT) tear, full-thickness (FT) tear-by 3D Dixon fat fraction (3D-FF); 2D fat fraction (2D-FF); and 2D Goutallier grade (2D-GG) at the Y-shaped view, and 1.4cm and 2.8cm medial to the Y-shaped view. Stratified by STT status to determine (2) correlation of 3D-FF with 2D-FF and 2D-GG and (3) inter-rater reliability at and medial to the Y-shaped view. Forty-five volunteers ≥ 60years recruited prospectively received shoulder MRI. 3D-FF and 2D-FF were measured on 6-point-Dixon MRI by three trainees. Goutallier grade was assessed on T1-weighted MRI by three fellowship-trained diagnostic radiologists. Descriptive, reliability, and correlation analyses were performed. Groups showed no difference in age. The FT group showed higher (p < 0.05) mean 3D-FF (14.09% ± 10.99%), mean 2D-FF (1.4cm medial to Y-shaped view, 14.91% ± 12.11%; 2.8cm medial to Y-shaped view, 13.32% ± 9.48%), and mean 2D-GG (Y-shaped view, 1.71 ± 0.78; 1.4cm medial to Y-shaped view, 1.71 ± 0.69; 2.8cm medial to Y-shaped view, 1.71 ± 0.72), relative to Intact/PT groups. 3D-FF showed strong correlation with 2D-FF among all groups/all analyses (rho, 0.80-0.98; p < 0.001). 3D-FF showed strong correlation with 2D-GG for all FT group analyses (rho, 0.85-0.91; p < 0.05). 3D-FF showed moderate-to-strong correlation considering all Intact/PT group analyses (rho, 0.51-0.79; p < 0.50). Dixon fat fraction showed excellent reliability for all groups (≥ 0.884, intraclass correlation coefficient). Goutallier grade showed excellent reliability for FT group (0.771, weighted Fleiss's kappa) but poor (0.294) and fair (0.502) for Intact and PT groups, respectively. Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration has merit for continued use in clinical populations requiring potential rotator-cuff-repair surgery. However, Dixon fat fraction should be prioritized for use in research over Goutallier grade due to superior reliability.

Evaluation of muscle mass and intramuscular fatty infiltration in dogs with hypercortisolism and their association with prognosis.

Muscle atrophy and intramuscular fatty infiltration, as well as their association with prognosis, have not been quantified in dogs with spontaneous hypercortisolism (HC). To quantitatively evaluate muscle atrophy and IM fatty infiltration in dogs with HC and determine their prognostic impact. Fifty-three dogs with HC and 66 control dogs without HC. Retrospective cohort study. Medical records and computed tomography images obtained between 2014 and 2021 were evaluated. Kaplan-Meier curves and log-rank tests were used to analyze the effect of muscle atrophy and IM fatty infiltration on the prognosis of dogs with HC. Dogs with HC showed lower visually measured cross-sectional area (VCSA) and cross-sectional area based on attenuation (HCSA) than control dogs (median [interquartile range {IQR}]: 50.3 mm2/mm [36.2-67.8] vs 66.7 mm2/mm [48.0-85.9]; P < .001; 30.4 mm2/mm [13.7-57.2] vs 54.8 mm2/mm [39.7-71.5]; P < .001, respectively). Dogs with HC had lower epaxial muscle attenuation (L3HU) than control dogs (median [IQR]: 21.2 Hounsfield [HU] [12.4-28.2] vs 33.2 HU [22.6-43.6]; P < .001). Dogs with HC with lower HCSA or L3HU had shorter survival (median [IQR]: 670 days [222-673] vs 949 days [788-1074], P < .01; 523 days [132-670] vs 949 days [756-1074], P < .01, respectively) but not lower VCSA (median [IQR]: 673 days [132-788] vs 949 days [523 to not applicable]; P = .30). Hypercortisolism in dogs causes muscle atrophy and IM fatty infiltration and is associated with poor prognosis.

Shoulder &amp; Elbow

The April 2024 Shoulder &amp; Elbow Roundup360 looks at: Acute rehabilitation following traumatic anterior shoulder dislocation (ARTISAN): pragmatic, multicentre, randomized controlled trial; Prevalence and predisposing factors of neuropathic pain in patients with rotator cuff tears; Are two plates better than one? The clavicle fracture reimagined; A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution; Complication rates and deprivation go hand in hand with total shoulder arthroplasty; Longitudinal instability injuries of the forearm; A better than “best-fit circle” method for glenoid bone loss assessment; 3D supraspinatus muscle volume and intramuscular fatty infiltration after arthroscopic rotator cuff repair.

Association of mid-thigh quadriceps muscle quality with postoperative outcomes in patients with hip osteoarthritis undergoing total hip arthroplasty: a retrospective cohort study.

Muscle quality is more important than muscle mass for assessing physical function. Computed tomography (CT) is used to evaluate intramuscular fatty infiltration. The mid-thigh quadriceps CT attenuation values (CTV) expressed in Hounsfield units (HU) negatively correlate with physical function. Patients with hip osteoarthritis (HOA) have lower extremity muscle atrophy, including decreased cross-sectional area (CSA), CTV, and muscle strength. Using preoperative CT images, we investigated the association between mid-thigh quadriceps CSA, CTV, and postoperative outcomes in patients with HOA. This study included 62 patients who had unilateral HOA (62 hips) and underwent total hip arthroplasty (THA). We investigated the association between preoperative and postoperative Japanese Orthopaedic Association (JOA) hip scores, 12-item Short Form survey (SF-12), mid-thigh quadriceps CSA, and CTV. The mean age was 64.7 ± 10.1years, with 15 men (24.2%), and the mean body mass index was 24.3 ± 4.3kg/m2. Secondary HOA was present in 79.0% of patients. The mean CSA and CTV of the mid-thigh quadriceps on the operative side were 38.8 ± 9.8 cm2 and 40.3 ± 7.8 HU, respectively. Multiple regression analyses adjusted for age and sex showed that preoperative mid-thigh quadriceps CSA was not associated with preoperative and postoperative JOA hip scores or SF-12. The preoperative mid-thigh quadriceps CTV was associated with the postoperative JOA hip score in the gait ability domain and SF-12 in the physical component summary domain. Preoperative muscle quality is associated with postoperative outcomes in patients who have HOA regardless of age and sex.

Is 3D Quantitative MRI the Next Tool to Evaluate Rotator Cuff Musculature and Other Muscle Pathology?: Commentary on an article by Junjie Xu, MD, PhD, et al.: "Longitudinal Changes in Overall 3D Supraspinatus Muscle Volume and Intramuscular Fatty Infiltration After Arthroscopic Rotator Cuff Repair".

Is 3D Quantitative MRI the Next Tool to Evaluate Rotator Cuff Musculature and Other Muscle Pathology?: Commentary on an article by Junjie Xu, MD, PhD, et al.: "Longitudinal Changes in Overall 3D Supraspinatus Muscle Volume and Intramuscular Fatty Infiltration After Arthroscopic Rotator Cuff Repair".

Longitudinal Changes in Overall 3D Supraspinatus Muscle Volume and Intramuscular Fatty Infiltration After Arthroscopic Rotator Cuff Repair.

There is considerable debate regarding the longitudinal changes in overall rotator cuff (RC) muscle atrophy and intramuscular fatty infiltration (FI) following RC repair. We analyzed the longitudinal changes in overall 3D supraspinatus muscle volume and intramuscular FI (3D FI) to determine the effect of tear size and repair integrity on 3D muscle volume and intramuscular FI. Forty-seven patients who underwent arthroscopic RC repair and had 6-point Dixon shoulder magnetic resonance imaging (MRI) preoperatively and 3 and 12 months postoperatively were enrolled. The 3D supraspinatus muscle volume and intramuscular FI were calculated at the 3 time points, and their changes over time were evaluated in the entire cohort as well as according to tear size and repair integrity. The agreement of the difference between time points among the patients was assessed by Bland-Altman analysis. In the cohort as a whole, there were no significant longitudinal changes in the 3D supraspinatus volume (19.65 ± 7.26 to 19.48 ± 7.46 cm 3 , p = 0.911) or 3D FI (17.18% ± 8.85% to 17.30% ± 9.18%, p = 0.977) from preoperatively to the final 12-month time point, overall and in the tear size and repair integrity subgroups. The 3D supraspinatus volume was significantly decreased at 3 months (17.39 ± 6.12 cm 3 , p < 0.001) but then increased again by 12 months (p < 0.001), reaching a value similar to the preoperative level. The 3D FI had a small increase at 3 months (18.18% ± 9.65%, p = 0.097) but subsequently decreased slightly again (p = 0.211), such that there were no significant longitudinal changes. The differences in the 3D supraspinatus volume and FI between these time points showed high agreement among patients. The overall 3D supraspinatus volume and 3D FI showed no longitudinal change between the preoperative baseline and the 12-month follow-up after arthroscopic RC repair. Tear size and repair integrity had no impact on the longitudinal patterns of muscle volume and intramuscular FI changes. The 3D supraspinatus volume decreased during the first 3 months but recovered to baseline at 12 months postoperatively; 3D FI was relatively stable throughout the 12 months of follow-up after repair. Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Myosteatosis and bone marrow adiposity are not associated among postmenopausal women with fragility fractures.

Although paravertebral intramuscular fatty infiltration (known as myosteatosis) following a vertebral fracture is well-known, scarce data are available regarding interactions between muscle, bone, and other fat depots. Based on a homogeneous cohort comprising postmenopausal women with or without a history of fragility fracture, we aimed to better depict the interrelationship between myosteatosis and bone marrow adiposity (BMA). 102 postmenopausal women were included, 56 of whom had a fragility fracture. Mean proton density fat fraction (PDFF) was measured in the psoas (PDFFPsoas) and paravertebral (PDFFParavertebral) muscles at the lumbar level, as well as in the lumbar spine and non-dominant hip using chemical shift encoding-based water-fat imaging. Visceral adipose tissue (VAT) and total body fat (TBF) were assessed using dual X-ray absorptiometry. Statistical models were adjusted for age, weight, height (all comparisons), and bone mineral density (when considering BMA). PDFF in the psoas and paravertebral muscles was higher in the fracture group compared to controls even after adjustment for age, weight, and height (PDFFPsoas = 17.1 ± 6.1% versus 13.5 ± 4.9%, p=0.004; PDFFParavertebral = 34.4 ± 13.6% versus 24.9 ± 8.8%, p=0.002). Higher PDFFParavertebral was associated with lower PDFF at the lumbar spine (β = -6.80 ± 2.85, p=0.022) among controls but not in the fracture group. In both groups, a significant relationship between higher PDFFPsoas and higher VAT was observed (β = 20.27 ± 9.62, p=0.040 in the fracture group, and β = 37.49 ± 8.65, p<0.001 in the control group). Although solely observed among controls, a similar relationship was observed between PDFFParavertebral and TBF (β = 6.57 ± 1.80, p<0.001). No significant association was observed between BMA and other fat depots. Myosteatosis is not associated with BMA among postmenopausal women with fragility fractures. Whereas myosteatosis was associated with other fat depots, BMA appears uniquely regulated.

WNT7A suppresses adipogenesis of skeletal muscle mesenchymal stem cells and fatty infiltration through the alternative Wnt-Rho-YAP/TAZ signaling axis.

Intramuscular fatty infiltration in muscle injuries and diseases, caused by aberrant adipogenesis of fibro-adipogenic progenitors, negatively impacts function. Intramuscular delivery of wingless-type MMTV integration site family 7a (WNT7A) offers a promising strategy to stimulate muscle regeneration, but its effects on adipogenic conversion of fibro-adipogenic progenitors remain unknown. Here, we show that WNT7A decreases adipogenesis of fibro-adipogenic progenitors (FAPs) by inducing nuclear localization of Yes-associated protein (YAP) through Rho in a β-CATENIN-independent manner and by promoting nuclear retention of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in differentiating FAPs. Furthermore, intramuscular injection of WNT7A invivo effectively suppresses fatty infiltration in mice following glycerol-induced injury. Our results collectively suggest WNT7A as a potential protein-based therapeutic for diminishing adipogenesis of FAPs and intramuscular fatty infiltration in pathological muscle injuries or diseases.

Supraspinatus fatty infiltration on MRI among older adults receiving physical therapy as initial management for clinically suspected rotator cuff tear: A pilot study.

Rotator cuff (RC) tear is common among adults ≥60 years, with supraspinatus tear most common. Intramuscular fatty infiltration (FI) on imaging is predictive of long-term outcomes following RC tear. Physical therapists routinely diagnose RC tear only by clinical examination since most do not order imaging studies. Thus, there is limited knowledge about FI in older populations receiving physical therapy (PT) for initial management of RC tear. The primary objective of our pilot study is to determine longitudinal differences in supraspinatus FI over time among older adults receiving PT (PT cohort) for initial management of RC tear relative to older adult volunteers (control cohort), and with secondary objective to evaluate longitudinal self-reported shoulder function over time. This was a prospective longitudinal cohort study. Forty adults, 60-85 years, were enrolled at baseline; one follow-up visit at ≥6 months. Shoulder magnetic resonance imaging and clinical screening for Charlson comorbidity index (CCI), body mass index (BMI), and American Shoulder and Elbow Surgeon (ASES) score were completed at baseline and follow-up visits. Supraspinatus FI was evaluated by 6-point Dixon fat fraction and Goutallier grade. PT (n = 15) and control (n = 25) cohorts were stratified by supraspinatus status: Intact (no tear), partial-thickness tear (PTT), and full-thickness tear (FTT). Comparisons within cohort were performed by Kruskal-Wallis test and between cohorts by Mann-Whitney U-test. Interobserver reliability was performed for Dixon fat fraction and Goutallier grade. PT cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for FTT by Goutallier grade (no tear, 0.5 ± 0.5; PTT, 1.1 ± 0.2; and FTT, 1.5 ± 0.5; P = 0.033) and by Dixon fat fraction (no tear, 4.6% ± 1.4%; PTT, 6.1% ± 1.9%; and FTT, 6.7% ± 2.5%; P = 0.430). Control cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for supraspinatus FTT by Dixon fat fraction (no tear, 5.8% ± 1.2%; PTT, 7.1% ± 6.3%; and FTT, 21.4% ± 10.4%; P = 0.034) and by Goutallier grade (no tear, 0.8 ± 0.5; PTT, 1.0 ± 0.6; and FTT, 2.4 ± 1.7; P = 0.141). No difference between similar PT and control cohort subgroups at baseline except no tear groups for ASES score (PT cohort, 58.9 ± 8.2; control cohort, 84.0 ± 21.9; P = 0.049). No differences were identified for Δ-Dixon fat fraction and Δ-Goutallier grade over time in the PT and control cohorts. PT cohort no tear subgroup showed significant improvement (P = 0.042) for Δ-ASES score over time relative to PTT and FTT subgroups; no difference for Δ-ASES score over time in the control cohort. Full-thickness RC tear showed higher levels of FI relative to PTT or no tear at baseline. Our pilot study's trend suggested that older adults receiving PT for initial management of RC tear have full-thickness RC tear for shorter duration based on relative lower levels of FI at baseline as compared to older adult volunteers with full-thickness RC tear. Our pilot study also found that older adults in the PT cohort with no tear had superior shoulder functional recovery by ASES score over time relative to full-thickness and PTTs.

Clinical characteristics of dysphagic inclusion body myositis

This study aimed to characterize dysphagic patients with inclusion body myositis (IBM) with cricopharyngeal bar (CPB) (n = 17; IBM-CPB(+)) by comparing their swallowing function and muscle magnetic resonance imaging data with IBM patients without CPB (n = 28; IBM-CPB(-)). IBM-CPB(+) patients were older at diagnosis and had more frequent obstruction-related dysphagia and stronger knee extension than IBM-CPB(-) patients. IBM-CPB(+) patients also had less intramuscular fatty infiltration than IBM-CPB(-) patients on T1-weighted magnetic resonance images of the rectus femoris (2.6% versus 10.3%, p < 0.05), vastus lateralis (27.8% versus 57.1%, p < 0.01), vastus intermedius (17.6% versus 43.5%, p < 0.01), vastus medialis (14.1% versus 39.1%, p < 0.01), deltoid (5.5% versus 18.7%, p < 0.05), biceps (6.6% versus 21.1%, p < 0.001), and triceps (12.9% versus 33.0%, p < 0.05). These findings suggest that IBM-CPB(+) patients were older, frequently exhibited obstruction-related dysphagia, had stronger knee extension, and had less fatty infiltration of the limb muscles compared to IBM-CPB(-) patients, and provide valuable information on the clinical subset of IBM-CBP(+) patients in order to expand the knowledge of the clinical heterogeneity in IBM.

FACS-isolation and Culture of Fibro-Adipogenic Progenitors and Muscle Stem Cells from Unperturbed and Injured Mouse Skeletal Muscle.

Fibro-adipogenic progenitor cells (FAPs) are a population of skeletal muscle-resident mesenchymal stromal cells (MSCs) capable of differentiating along fibrogenic, adipogenic, osteogenic, or chondrogenic lineage. Together with muscle stem cells (MuSCs), FAPs play a critical role in muscle homeostasis, repair, and regeneration, while actively maintaining and remodeling the extracellular matrix (ECM). In pathological conditions, such as chronic damage and muscular dystrophies, FAPs undergo aberrant activation and differentiate into collagen-producing fibroblasts and adipocytes, leading to fibrosis and intramuscular fatty infiltration. Thus, FAPs play a dual role in muscle regeneration, either by sustaining MuSC turnover and promoting tissue repair or contributing to fibrotic scar formation and ectopic fat infiltrates, which compromise the integrity and function of the skeletal muscle tissue. A proper purification of FAPs and MuSCs is a prerequisite for understanding the biological role of these cells in physiological as well as in pathological conditions. Here, we describe a standardized method for the simultaneous isolation of FAPs and MuSCs from limb muscles of adult mice using fluorescence-activated cell sorting (FACS). The protocol describes in detail the mechanical and enzymatic dissociation of mononucleated cells from whole limb muscles and injured tibialis anterior (TA) muscles. FAPs and MuSCs are subsequently isolated using a semi-automated cell sorter to obtain pure cell populations. We additionally describe an optimized method for culturing quiescent and activated FAPs and MuSCs, either alone or in coculture conditions.

Cervical Multifidus Morphology and Quality Are Not Associated with Clinical Variables in Women with Fibromyalgia: An Observational Study

Abstract Objective Some studies have reported the presence of histological alterations, such as myofiber disorganization and abnormalities in the number and shape of mitochondria, in patients with fibromyalgia syndrome (FMS). Although Ultrasound imaging (US) is used to quantitatively characterize muscle tissues, US studies in patients with FMS are lacking. Therefore, we aimed to describe morphological and qualitative cervical multifidus (CM) muscle US features in women with FMS and to assess their correlation with clinical indicators. Design Observational study. Setting AFINSYFACRO Fibromyalgia Association (Madrid, Spain). Subjects Forty-five women with FMS participated. Methods Sociodemographic variables (e.g., age, height, weight, body mass index) and clinical outcomes (e.g., pain as assessed on a numerical pain rating scale, evolution time, pain-related disability as assessed by the Fibromyalgia Impact Questionnaire) were collected. Images were acquired bilaterally at the cervical spine (C4–C5 level) and measured by an experienced examiner for assessment of muscle morphology (e.g., cross-sectional area, perimeter, and shape) and quality (mean echo intensity and intramuscular fatty infiltration). Side-to-side comparisons and a correlational analysis were conducted. Results No significant side-to-side differences were found for morphology or quality features (P &amp;gt; 0.05). None of the clinical indicators were associated with US characteristics (all, P &amp;gt; 0.05). Conclusion Our results showed no side-to-side differences for CM morphology and quality as assessed with US. No associations between CM muscle morphology or quality and Fibromyalgia Impact Questionnaire, pressure pain threshold, numerical pain rating scale score, or evolution time were observed. Our preliminary data suggest that muscle morphology is not directly related to pain and pain-related disability in women with FMS.

Erratum to: "Intramuscular fatty infiltration and physical function in controlled acromegaly".

Erratum to: "Intramuscular fatty infiltration and physical function in controlled acromegaly".

Clinical, Radiographic, and Genetic Analyses in a Population-Based Cohort of Adult Spinal Deformity in the Older Population.

ObjectiveThis study aimed to identify the sagittal parameters associated with health-related quality of life and genetic variations that increase the risk of adult spinal deformity (ASD) onset in the older population. MethodsWe recruited 120 participants who had a sagittal vertical axis > 50 mm in a sagittal imbalance study. Sagittal radiographic parameters, cross-sectional area, and intramuscular fatty infiltration using the Goutallier classification in the paraspinal lumbar muscles were evaluated. Functional scales included the self-reported Oswestry Disability Index (ODI), 36-item Short Form Health Survey (SF-36), and visual analogue scales (VAS) for back and leg pain. We performed whole-exome sequencing and an exome-wide association study using the 100 control subjects and 63 individuals with severe phenotypes of sagittal imbalance. ResultsPelvic incidence minus lumbar lordosis (PI–LL) mismatch was negatively associated with the SF-36 and positively correlated with ODI and VAS for back and leg pain. PI–LL was related to the quality and size of the paraspinal muscles, especially the multifidus muscle. We identified common individual variants that reached exome-wide significance using single-variant analysis. The most significant single-nucleotide polymorphism was rs78773460, situated in an exon of the SVIL gene (odds ratio, 9.61; p=1.15 × 10-9). ConclusionOlder age, higher body mass index, and a more significant PI–LL mismatch were associated with unfavorable results on functional scales. We found a genetic variation in the SVIL gene, which has been associated with the integrity of the cytoskeleton and the development of skeletal muscles, in severe ASD phenotypes. Our results help to elucidate the pathogenesis of ASD.

The biomechanical disadvantage of dysplastic hips.

Developmental dysplasia of the hip (DDH) is strongly associated with an increased risk for hip osteoarthritis. Skeletal deformities undeniably contribute to detrimental biomechanical loading in dysplastic hips, but cannot explain all types of damage and symptoms that patients with DDH experience. Characterizing the geometry and function of the muscles spanning the hip is a logical next step in our progression of knowledge about DDH pathomechanics. In this study, we compared skeletal geometry, muscle volumes, intramuscular fatty infiltration, moment arms, and isometric strength in patients with DDH (N = 20) to healthy controls (N = 15). Femoral coverage was significantly less in patients (p < 0.001, Cohen's d effect size = 2.2), femoral neck-shaft angles were larger (p = 0.001, d = 1.3), and hip joint centers (HJCs) were more lateral (p = 0.001, d = 1.3). These skeletal abnormalities were associated with smaller abductor muscle moment arms in patients with DDH (e.g., gluteus medius [GMED]: p = 0.001, d = 1.2). Patients with DDH also had larger GMED volumes (p = 0.02, d = 0.83), but no differences in fatty infiltration, compared to controls. Isometric strength of the hip abductors, extensors, and flexors was lower in patients, but not significantly different from controls. The abnormal skeletal geometry, lateralized HJC, and reduced muscle moment arms represent a chronic biomechanical disadvantage under which patients with DDH operate. This phenomenon causes increased demand on the abductor muscles and results in high medially and superiorly directed joint reaction forces, which can explain reports of superomedial femoral cartilage damage in patients. The abnormal muscle geometry and function, in context with abnormal skeletal structure, are likely strong, but underappreciated, contributors to damaging loads in DDH.

Prevalence of sarcopenia after remission of hypercortisolism and its impact on HRQoL.

Cushing's syndrome (CS) is associated with skeletal muscle structural and functional impairment which may persist long-term despite surgical removal of the source of cortisol excess. Prevalence of sarcopenia and its impact on Health-Related-Quality of Life (HRQoL) in 'cured' CS is not known. There is a need to identify easy biomarkers to help the clinicians recognise patients at elevated risk of suffering sustained muscle function. We studied 36 women with CS in remission, and 36 controls matched for age, body mass index, menopausal status, and level of physical activity. We analysed the skeletal muscle mass using dual-energy X-ray absorptiometry, muscle fat fraction using two-point Dixon magnetic resonance imaging and muscle performance and strength using the following tests: hand grip strength, gait speed, timed up and go and 30-s chair stand. We assessed HRQoL with the following questionnaires: SarQoL, CushingQoL, SF-36. We calculated the sarcopenia index (SI; serum creatinine/serum cystatin C × 100). Prevalence of sarcopenia, according to the European Working Group on Sarcopenia in Older People (EWGSOP), was greater in CS as compared with controls (19% vs. 3%; p < .05). Patients with sarcopenia had a lower SarQoL score than those without sarcopenia (61 ± 17 vs. 75 ± 14; p < .05), and scored worse on the items pain, easy bruising and worries on physical appearance (p < .05 for all comparisons) of the CushingQoL questionnaire. Patients with sarcopenia had poorer physical functioning on SF-36 than those without sarcopenia (60 ± 23 vs. 85 ± 15; p < .01). SI was lower in patients with sarcopenia than those without (71 ± 3 vs. 77 ± 2; p = .032), and was associated with intramuscular fatty infiltration, worse performance on the 30-s chair stand test, slower gait speed, and worse muscle weakness-related HRQoL, as measured using the SarQoL questionnaire (p < .05). The optimised cut-off value for the SI ratio to diagnose sarcopenia was 72, which yielded a sensitivity of 73% and a specificity of 90%. Sarcopenia is common in patients with CS in long-term remission, and associated with impaired quality of life. The SI is a potential biomarker allowing clinicians to identify patients at high risk of muscle dysfunction.

Targeting interleukin-1 for reversing fat browning and muscle wasting in infantile nephropathic cystinosis.

Background Ctns −/− mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Inflammatory cytokines such as interleukin (IL)‐1 trigger inflammatory cascades and may be an important cause for cachexia. We employed genetic and pharmacological approaches to investigate the effects of IL‐1 blockade in Ctns −/− mice.MethodsWe generated Ctns −/− Il1β −/− mice, and we treated Ctns −/− and wild‐type control mice with IL‐1 receptor antagonist, anakinra (2.5 mg/kg/day, IP) or saline as vehicle for 6 weeks. In each of these mouse lines, we characterized the cachexia phenotype consisting of anorexia, loss of weight, fat mass and lean mass, elevation of metabolic rate, and reduced in vivo muscle function (rotarod activity and grip strength). We quantitated energy homeostasis by measuring the protein content of uncoupling proteins (UCPs) and adenosine triphosphate in adipose tissue and skeletal muscle. We measured skeletal muscle fiber area and intramuscular fatty infiltration. We also studied expression of molecules regulating adipose tissue browning and muscle mass metabolism. Finally, we evaluated the impact of anakinra on the muscle transcriptome in Ctns −/− mice.ResultsSkeletal muscle expression of IL‐1β was significantly elevated in Ctns −/− mice relative to wild‐type control mice. Cachexia was completely normalized in Ctns −/− Il1β −/− mice relative to Ctns −/− mice. We showed that anakinra attenuated the cachexia phenotype in Ctns −/− mice. Anakinra normalized UCPs and adenosine triphosphate content of adipose tissue and muscle in Ctns −/− mice. Anakinra attenuated aberrant expression of beige adipose cell biomarkers (UCP‐1, CD137, Tmem26, and Tbx1) and molecules implicated in adipocyte tissue browning (Cox2/Pgf2α, Tlr2, Myd88, and Traf6) in inguinal white adipose tissue in Ctns −/− mice. Moreover, anakinra normalized gastrocnemius weight and fiber size and attenuated muscle fat infiltration in Ctns −/− mice. This was accompanied by correction of the increased muscle wasting signalling pathways (increased protein content of ERK1/2, JNK, p38 MAPK, and nuclear factor‐κB p65 and mRNA expression of Atrogin‐1 and Myostatin) and the decreased myogenesis process (decreased mRNA expression of MyoD and Myogenin) in the gastrocnemius muscle of Ctns −/− mice. Previously, we identified the top 20 differentially expressed skeletal muscle genes in Ctns −/− mice by RNAseq. Aberrant expression of these 20 genes have been implicated in muscle wasting, increased energy expenditure, and lipolysis. We showed that anakinra attenuated 12 of those top 20 differentially expressed muscle genes in Ctns −/− mice.ConclusionsAnakinra may provide a targeted novel therapy for patients with infantile nephropathic cystinosis.

Reliability of supraspinatus intramuscular fatty infiltration estimates on T1-weighted MRI in potential candidates for rotator cuff repair surgery: full-thickness tear versus high-grade partial-thickness tear.

Patients with supraspinatus high-grade partial-thickness tear or full-thickness tear are potential candidates for rotator cuff repair surgery. We sought (1) to compare supraspinatus intramuscular fatty infiltration between these groups by Goutallier grade, fuzzy C-means and an orthopaedic surgeon visible percentage estimate, (2) and to determine the reliability of each method. We performed a retrospective cross-sectional study of supraspinatus intramuscular fatty infiltration on T1-weighted MR images for 93 shoulders with either supraspinatus partial-thickness tear > 50% tendon thickness or full-thickness tear by Goutallier grade, fuzzy C-means and an orthopaedic surgeon visible percentage estimate, by two observers for each method. Descriptive statistics were performed to compare groups. Inter- and intra-observer reliability was determined. Correlative analysis among the three methods was performed. Significant differences of mean supraspinatus intramuscular fatty infiltration were present when comparing supraspinatus high-grade partial-thickness tear versus full-thickness tears by Goutallier grade (p = 0.004), fuzzy C-means (p = 0.002) and orthopaedic surgeon visible percentage estimate (p = 0.001). There was no significant difference for age (55.0 ± 11.1years versus 56.1 ± 9.6years) or sex (35.4% male versus 47.8% male) for supraspinatus high-grade partial-thickness tear and full-thickness tear, respectively. A significant difference existed among the subgroup of full-thickness tears stratified by tear size by all three methods (p < 0.020). Inter- and intra-observer reliability was Goutallier grade 0.590 and 0.624, fuzzy C-means 0.768 and 0.925 and orthopaedic surgeon visible percentage estimate 0.858 and 0.686, respectively. For shoulders with mean Goutallier grade ≥ 2.0, inter-observer reliability was 0.878 and 0.802 for fuzzy C-means and orthopaedic surgeon visible percentage estimate, respectively. A strong correlation was present among the three methods of supraspinatus FI analysis (rho ≥ 0.72). Supraspinatus full-thickness tears have higher amounts of intramuscular fatty infiltration compared to high-grade partial-thickness tear. Quantitative fuzzy C-means shows excellent inter-observer reliability for estimating supraspinatus intramuscular fat. Experienced orthopaedic surgeons' semi-quantitative estimation of supraspinatus visible intramuscular fat may offer improved reliability as compared to semi-quantitative Goutallier grade.

Targeting microRNA-mediated gene repression limits adipogenic conversion of skeletal muscle mesenchymal stromal cells.

Intramuscular fatty deposits, which are seen in muscular dystrophies and with aging, negatively affect muscle function. The cells of origin of adipocytes constituting these fatty deposits are mesenchymal stromal cells, fibroadipogenic progenitors (FAPs). We uncover a molecular fate switch, involving miR-206 and the transcription factor Runx1, that controls FAP differentiation to adipocytes. Mice deficient in miR-206 exhibit increased adipogenesis following muscle injury. Adipogenic differentiation of FAPs is abrogated by miR-206 mimics. Using a labeled microRNA (miRNA) pull-down and sequencing (LAMP-seq), we identified Runx1 as a miR-206 target, with miR-206 repressing Runx1 translation. In the absence of miR-206 in FAPs, Runx1 occupancy near transcriptional start sites of adipogenic genes and expression of these genes increase. We demonstrate that miR-206 mimicry invivo limits intramuscular fatty infiltration. Our results provide insight into the underlying molecular mechanisms of FAP fate determination and formation of harmful fatty deposits in skeletal muscle.

Intramuscular fatty infiltration and physical function in controlled acromegaly.

Patients with acromegaly show musculoskeletal symptoms which may persist despite disease control. Increased i.m. fat fraction is a known cause of muscle dysfunction in several disorders. To assess the degree of fat fraction in thigh muscles of controlled acromegaly patients and its relationship with muscle dysfunction. In a cross-sectional study, we included 36 patients with controlled acromegaly and 36 matched controls. We assessed the percentage of fat fraction in each thigh muscle, using MRI 2-point Dixon sequence, and muscle performance and strength using the gait speed, timed up and go, 30-s chair stand, and hand grip strength tests. We evaluated joint symptoms using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Intramuscular fat fraction was greater in patients than controls (P < 0.05 for muscle compartments, rectus femoris (RF), vastus intermedius (VI), adductor magnus (AM) and semimembranosus). Patients had slower gait speed and poorer performance on the 30-s chair stand and timed up and go tests than controls (P < 0.05). The greater fat fraction in the combined anterior-posterior compartment and in each muscle was associated with worse performance on timed up and go (P < 0.05). The fat fraction in the anterior-posterior compartment predicted performance on timed up and go after adjusting for muscle area, IGF-I and WOMAC functional and pain scores (β = 0.737 P < 0.001). Patients with controlled acromegaly have greater thigh i.m. fatty infiltration, which is associated with muscle dysfunction. Futures studies are needed to elucidate the mechanisms underlying this relationship.