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Rationale: Allan-Herndon-Dudley syndrome (AHDS) results from a pathogenic variant in the hemizygous subunit of the SLC16A2 gene, which encodes monocarboxylate transporter 8 and follows an X-linked recessive pattern. AHDS manifests as neuropsychomotor developmental delay, intellectual disability, movement disorders, and thyroid hormone abnormalities. It is frequently misdiagnosed as cerebral palsy or hypothyroidism., Patient Concerns: A 9-month-old male infant exhibited poor head control, hypodynamia, motor retardation, hypertonic limbs, and thyroid abnormalities. Despite levothyroxine supplementation and rehabilitation therapy, no improvements were observed. Whole-exome sequencing identified a novel nonsense mutation in SLC16A2 (c.124G > T, p.E42X), which unequivocally established the diagnosis., Diagnoses: AHDS was confirmed., Interventions: Levothyroxine treatment commenced early in infancy, followed by 3 months of rehabilitation therapy, starting at 5 months of age. The combined administration of levothyroxine and methimazole was initiated at 1 year and 10 months of age, respectively., Outcomes: While improvements were noted in thyroid hormone levels, neurological developmental delays persisted., Lessons: AHDS should be considered in patients presenting with atypical neurological features and thyroid hormone abnormalities such as elevated triiodothyronine and decreased thyroxine levels. The early utilization of exome sequencing aids in prompt diagnosis. The identified SLC16A2 nonsense mutation correlates with severe neurological phenotypes and adds to the spectrum of genetic variations associated with AHDS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hand weakness is a frequent chief concern in neurology practice. We report a case of a 55-year-old woman presenting with a chronic, gradually worsening right hand weakness and atrophy, selectively affecting the thenar muscles, without any sensory symptoms. She had a history of carpal tunnel syndrome and previously underwent surgical carpal tunnel release. This case delves into the differential diagnosis of hand weakness and atrophy, emphasizing the significance of myotomal innervation in intrinsic hand muscles. Furthermore, it outlines a systematic approach to diagnosing an uncommon cause for a common clinical presentation, offering a comprehensive differential diagnosis, and exploring various possible causes.

Brachio-cervical inflammatory myopathy (BCIM) is a rare inflammatory myopathy characterized by dysphagia, bilateral upper limb atrophy, limb-girdle muscle weakness, and myositis-specific antibody (MSA) negativity. BCIM has a low incidence and is commonly associated with autoimmune diseases. We present a case report of a 55-year-old man with progressive upper limb weakness and atrophy, diagnosed with flail arm syndrome (FAS). The initial electromyography revealed extensive spontaneous muscle activity and increased duration of motor unit potentials (MUPs). During follow-up, evidence of myogenic damage was observed, as indicated by a decreased duration of MUPs in the right biceps muscle. Laboratory and genetic testing ruled out hereditary or acquired diseases. Negative serological antibodies for myasthenia gravis. Hereditary or acquired diseases were ruled out through laboratory and genetic testing. Whole-body muscle magnetic resonance imaging (MRI) showed extensive edema and fat replacement in the bilateral upper limbs, scapular, and central axis muscles, while the lower extremities were relatively mildly affected. Muscle biopsy revealed numerous foci of inflammatory cells distributed throughout the muscle bundle, with predominant CD20, CD138, and CD68 expression, accompanied by a light infiltration of CD3 and CD4 expression. The muscle weakness improved with the combination of oral prednisone (initially 60 mg/day, tapered) and methotrexate (5 mg/week) treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Wei, Han, Wang, Wang and Yu.)

Background Context: Atrophy of the paraspinal musculature (PM) as well as generalized sarcopenia are increasingly reported as important parameters for clinical outcomes in the field of spine surgery. Despite growing awareness and potential similarities between both conditions, the relationship between "generalized" and "spine-specific" sarcopenia is unclear., Purpose: To investigate the association between generalized and spine-specific sarcopenia., Study Design: Retrospective cross-sectional study., Patient Sample: Patients undergoing lumbar spinal fusion surgery for degenerative spinal pathologies., Outcome Measures: Generalized sarcopenia was evaluated with the short physical performance battery (SPPB), grip strength, and the psoas index, while spine-specific sarcopenia was evaluated by measuring fatty infiltration (FI) of the PM., Methods: We used custom software written in MATLAB® to calculate the FI of the PM. The correlation between FI of the PM and assessments of generalized sarcopenia was calculated using Spearman's rank correlation coefficient (rho). The strength of the correlation was evaluated according to established cut-offs: negligible: 0-0.3, low: 0.3-0.5, moderate: 0.5-0.7, high: 0.7-0.9, and very high≥0.9. In a Receiver Operating Characteristics (ROC) analysis, the Area Under the Curve (AUC) of sarcopenia assessments to predict severe multifidus atrophy (FI≥50%) was calculated. In a secondary analysis, factors associated with severe multifidus atrophy in nonsarcopenic patients were analyzed., Results: A total of 125 (43% female) patients, with a median age of 63 (IQR 55-73) were included. The most common surgical indication was lumbar spinal stenosis (79.5%). The median FI of the multifidus was 45.5% (IQR 35.6-55.2). Grip strength demonstrated the highest correlation with FI of the multifidus and erector spinae (rho=-0.43 and -0.32, p<.001); the other correlations were significant (p<.05) but lower in strength. In the AUC analysis, the AUC was 0.61 for the SPPB, 0.71 for grip strength, and 0.72 for the psoas index. The latter two were worse in female patients, with an AUC of 0.48 and 0.49. Facet joint arthropathy (OR: 1.26, 95% CI: 1.11-1.47, p=.001) and foraminal stenosis (OR: 1.54, 95% CI: 1.10-2.23, p=.015) were independently associated with severe multifidus atrophy in our secondary analysis., Conclusion: Our study demonstrates a low correlation between generalized and spine-specific sarcopenia. These findings highlight the risk of misdiagnosis when relying on screening tools for general sarcopenia and suggest that general and spine-specific sarcopenia may have distinct etiologies., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To assess the feasibility of long-term muscle monitoring, we implemented an AI-guided segmentation approach on clinically indicated Computed Tomography (CT) examinations conducted throughout the hospitalization period of patients admitted to the intensive care unit (ICU) with acute pancreatitis (AP). In addition, we aimed to investigate the potential of muscle monitoring for early detection of patients at nutritional risk and those experiencing adverse outcomes. This cohort served as a model for potential integration into clinical practice., Materials: Retrospective cohort study including 100 patients suffering from AP that underwent a minimum of three CT scans during hospitalization, totaling 749 assessments. Sequential segmentation of psoas muscle area (PMA) was performed and was relative muscle loss per day for the entire monitoring period, as well as for the interval between each consecutive scan was calculated. Subgroup and outcome analyses were performed including ANOVA. Discriminatory power of muscle decay rates was evaluated using ROC analysis., Results: Monitoring PMA decay revealed significant long-term losses of 48.20% throughout the hospitalization period, with an average daily decline of 0.98%. Loss rates diverged significantly between survival groups, with 1.34% PMA decay per day among non-survivors vs. 0.74% in survivors. Overweight patients exhibited significantly higher total PMA losses (52.53 vs. 42.91%; p = 0.02) and average PMA loss per day (of 1.13 vs. 0.80%; p = 0.039). The first and the maximum decay rate, in average available after 6.16 and 17.03 days after ICU admission, showed convincing discriminatory power for survival in ROC analysis (AUC 0.607 and 0.718). Both thresholds for maximum loss (at 3.23% decay per day) and for the initial loss rate (at 1.98% per day) proved to be significant predictors of mortality., Conclusions: The innovative AI-based PMA segmentation method proved robust and effortless, enabling the first comprehensive assessment of muscle wasting in a large cohort of intensive care pancreatitis patients. Findings revealed significant muscle wasting (48.20% on average), particularly notable in overweight individuals. Higher rates of initial and maximum muscle loss, detectable early, correlated strongly with survival. Integrating this tool into routine clinical practice will enable continuous muscle status tracking and early identification of those at risk for unfavorable outcomes., (© 2024. The Author(s).)

Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disorder characterized by peripheral thyrotoxicosis and severe cognitive and motor disability due to cerebral hypothyroidism. 3,3’,5-triiodothyroacetic acid (Triac) was shown to improve peripheral thyrotoxicosis but data on neurodevelopmental outcome are scarce. We present a case of MCT8 deficiency and the experience with Triac focusing on change in neurodevelopmental and peripheral features. A five-month-old boy was referred because of feeding difficulty, central hypotonia and global developmental delay. Despite six months of physiotherapy, physical developmental milestones did not improve, and distal muscle tone was increased. A hemizygous pathogenic variant in SLC16A2 was found and MCT8 deficiency was confirmed at 19-months. Thyroid stimulating hormone was 2.83 mIU/mL, free thyroxine 6.24 pmol/L (N=12-22) and free triiodothyronine (FT3) 15.65pmol/L (N=3.1-6.8). He had tachycardia, blood pressure and transaminases were elevated. Triac was started at 21-months. Two weeks after treatment, FT3 dramatically decreased, steady normal serum FT3 was achieved at 28-months. Assessment of neurodevelopmental milestones and signs of hyperthyroidism were evaluated at baseline, 6 months and 12 months after treatment. Signs of hyperthyroidism were improved by 6 months. Developmental composite scores of Bayley Scales of Infant Developmental 3 rd Edition remained the same but important developmental milestones (head control, recognition of caregiver, response to his name) were attained, regression in the attained milestones were not observed. Initial dose, management protocol for Triac and research into its efficacy on neurodevelopmental signs in MCT8 deficiency are progressing. This case presents evidence that Triac may resolve peripheral thyrotoxicosis successfully and may slow neurodevelopmental regression, while some developmental milestones were achieved after one year of treatment., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Physiological stress during injury and surgery negatively impacts protein balance and muscle mass maintenance. Adequate perioperative protein intake may attenuate muscle atrophy to maintain and facilitate functional recovery, particularly in older adults; yet, screening tools routinely used in clinical settings do not specifically assess protein intake when assessing nutrition risk. Although assessing malnutrition is a priority, suboptimal protein intake in non-malnourished patients should also be identified given protein's critical role in muscle health. This opinion paper highlights the potential for using a clinically appropriate protein-focused screener for rapid and efficient characterization of protein intake., Competing Interests: Declaration of competing interest A.T.C., O.K.C., and N.R.R. have no conflicts of interest to disclose., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

A 63-year-old man diagnosed with mixed-type cervical spondylotic amyotrophy exhibited severe atrophy in the right biceps brachii, teres major, and intrinsic hand muscles, resulting in level 3 muscle weakness. Magnetic resonance imaging showed symmetrical high signal, also referred to as the snake eye sign. Previously, he was erroneously diagnosed with amyotrophic lateral sclerosis. He had undergone anterior cervical surgery 7 years prior. At present, his right upper limb muscles display minimal atrophy compared with the left, with muscle strength nearing level 4, which is considered normal. We believe that prompt surgical intervention on diagnosis of cervical spondylotic amyotrophy, along with comprehensive postsurgery rehabilitation, can halt further deterioration of the condition and accelerate recovery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The monocarboxylate transporter 8 (MCT8) plays a vital role in maintaining brain thyroid hormone homeostasis. This transmembrane transporter is expressed at the brain barriers, as the blood-brain barrier (BBB), and in neural cells, being the sole known thyroid hormone-specific transporter to date. Inactivating mutations in the MCT8 gene (SLC16A2) cause the Allan-Herndon-Dudley Syndrome (AHDS) or MCT8 deficiency, a rare X-linked disease characterized by delayed neurodevelopment and severe psychomotor disorders. The underlying pathophysiological mechanisms of AHDS remain unclear, and no effective treatments are available for the neurological symptoms of the disease., Methods: Neurovascular unit ultrastructure was studied by means of transmission electron microscopy. BBB permeability and integrity were evaluated by immunohistochemistry, non-permeable dye infiltration assays and histological staining techniques. Brain blood-vessel density was evaluated by immunofluorescence and magnetic resonance angiography. Finally, angiogenic-related factors expression was evaluated by qRT-PCR. The studies were carried out both in an MCT8 deficient subject and Mct8/Dio2KO mice, an AHDS murine model, and their respective controls., Results: Ultrastructural analysis of the BBB of Mct8/Dio2KO mice revealed significant alterations in neurovascular unit integrity and increased transcytotic flux. We also found functional alterations in the BBB permeability, as shown by an increased presence of peripheral IgG, Sodium Fluorescein and Evans Blue, along with increased brain microhemorrhages. We also observed alterations in the angiogenic process, with reduced blood vessel density in adult mice brain and altered expression of angiogenesis-related factors during brain development. Similarly, AHDS human brain samples showed increased BBB permeability to IgG and decreased blood vessel density., Conclusions: These findings identify for the first time neurovascular alterations in the MCT8-deficient brain, including a disruption of the integrity of the BBB and alterations in the neurovascular unit ultrastructure as a new pathophysiological mechanism for AHDS. These results open a new field for potential therapeutic targets for the neurological symptoms of these patients and unveils magnetic resonance angiography as a new non-invasive in vivo technique for evaluating the progression of the disease., (© 2023. The Author(s).)

Objective: We present the first wearable sensor designed for frequent monitoring of muscle atrophy and validate performance upon canonical phantoms., Methods: Our approach relies on Faraday's law of induction and exploits the dependence of magnetic flux density on cross-sectional area. We employ wrap-around transmit and receive coils that stretch to fit changing limb sizes using conductive threads (e-threads) in a novel zig zag pattern. Changes in the loop size result in changes in the magnitude and phase of the transmission coefficient between loops., Results: Simulation and in vitro measurement results are in excellent agreement. As a proof-of-concept, a cylindrical calf model for an average-sized subject is considered. The frequency of 60 MHz is selected via simulation for optimal limb size resolution in magnitude and phase while remaining in the inductive mode of operation. We can monitor muscle volume loss of up to 51%, with an approximate resolution of 0.17 dB and 1.58° per 1% volume loss. In terms of muscle circumference, we achieve resolution of 0.75 dB and 6.7° per centimeter. Thus, we can monitor small-scale changes in overall limb size., Conclusion: This is the first known approach for monitoring muscle atrophy with a sensor designed to be worn. Additionally, this work brings forward innovations in creating stretchable electronics from e-threads (as opposed to inks, liquid metal, or polymer)., Significance: The proposed sensor will provide improved monitoring for patients suffering from muscle atrophy. The stretching mechanism can be seamlessly integrated into garments which creates unprecedented opportunities for future wearable devices.

Objectives: The differential diagnosis between idiopathic inflammatory myopathies (IIM) and muscular dystrophies (MD) may be challenging. We analysed the potential role of muscular magnetic resonance imaging (MRI) in the differential diagnosis between IIM and MD., Methods: MRI of patients (91 IIM and 43 MD), studied with a standardised protocol, have been collected. The presence of oedema, muscular atrophy and intramuscular adipose changes were evaluated. Moreover, we computed a composite score for each MRI item to better discriminate between the two diseases., Results: Oedema was significantly more prevalent in IIM compared with MD in pelvis muscles (p<0.001), anterior lodge and medial lodges (p=0.044) of the thighs. Adipose infiltration/substitution and muscular atrophy were more prevalent in MD, in particular adipose tissue was prevalent in all the compartments of the thighs (p<0.05), atrophy was prevalent at the thighs and pelvis muscles (p<0.001). The probability of IIM increased with higher oedema score and decreased with higher atrophy and intramuscular adipose infiltration/substitution scores., Conclusions: A different distribution of muscular involvement between IIM and MD has been identified. Muscular MRI may be useful in the differential diagnosis, potentially reducing the number of muscular biopsies that may be reserved only for doubtful cases.

Purpose: Anthropometric indices are simple indicators of patient nutritional status. However, the association between these indices and skeletal-muscle atrophy in patients with stable chronic obstructive pulmonary disease (COPD) has not been fully investigated. In this study, we evaluated this association., Patients and Methods: We recruited 123 outpatients with stable COPD from a general hospital in China from 2020 to 2021. We recorded their demographic characteristics, including age, sex, course of illness, dyspnea score, body mass index (BMI), force expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), smoking status, and severity grading. In addition, patients' anthropometric indices, including fat-free mass index (FFMI) and appendicular skeletal-muscle mass index (ASMI), were measured using a body composition analyzer, and measurements were taken of the triceps skinfold (TSF), midarm circumference (MAC), and calf circumference (CC). We drew and analyzed a receiver operating characteristic (ROC) curve to identify the best intercept point value for the assessment of skeletal-muscle atrophy., Results: The TSF, MAC, CC, FFMI, and ASMI of COPD patients were 1.08 ± 0.44 cm, 26.39 ± 2.92 cm, 34.5 ± 3.06 cm, 17.49 ± 1.86 kg/m 2 , and 8.17 ± 0.90 kg/m 2 , respectively. These anthropometric indices had a significant positive correlation with skeletal-muscle mass (correlation values, 0.481-0.820). CC was strongly correlated with both FFMI and ASMI. The ROC curve showed an area-under-the-curve (AUC) value of 0.873-0.959., Conclusion: Anthropometric indices were correlated with skeletal-muscle mass. CC showed the best diagnostic value in COPD patients, suggesting its effectiveness as a simple method for assessing skeletal-muscle atrophy and identifying patients with a noticeable reduction in muscle mass. Such patients require early, multidisciplinary intervention., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Han et al.)

Background: Enteral feeding intolerance, energy-protein malnutrition, and muscle wasting are common conditions in the critical care setting. The primary aim of this study was to investigate the effect of synbiotic supplementation on enteral feed volume, energy and protein homeostasis, and muscle mass maintenance in critically ill adult patients., Methods: A consecutive of 42 patients admitted to the Edalatian Medical ICU, requiring enteral nutrition (EN), were prospectively randomized to receive the synbiotic capsule (containing a combination of Lactobacillus, Bifidobacterium, Streptococcus, and fructooligosaccharides) or placebo (21 patients in each group) for a maximum of 14 days. Enteral intolerance and energy homeostasis were evaluated on a daily basis. Nitrogen balance and 24-h urine creatinine excretion were recorded on days 1 and 14. Mid-arm circumference was recorded every 3 days., Results: Mean EN volume, energy, and protein intake per day were 962.5 ± 533.82 ml, 770 ± 427.05 kcal, and 38.5 ± 21.35 g (fourth day) vs. 590 ± 321.1 ml, 472 ± 256.81 kcal, and 23.6 ± 12.84 g (first day) in the synbiotic group (p < 0.05). Changes in the placebo group were not statistically significant. On day 1, nitrogen balance (NB) was - 19.84 ± 8.03 in the synbiotic vs. - 10.99 ± 9.12 in the placebo group (p = 0.003). On day 14, NB was - 14.18 ± 13.05 in the synbiotic and - 9.59 ± 7.71 in the placebo group (p = 0.41). Mid-arm circumference (MAC), 24-h urine creatinine, and creatinine-height index were almost steady in the synbiotic group, while they decreased in the placebo group., Conclusion: Overall, it can be concluded that enteral nutrition supplemented with synbiotics has no statistically significant effect on energy and protein homeostasis and muscle mass maintenance of critically ill patients on day 14, but it can increase enteral feed volume and energy and protein intake during the first 4 days of ICU admission., Trial Registration: The trial protocol has been approved in Iranian Registry of Clinical Trials on March 17, 2019. The registration reference is IRCT20190227042857N1., (© 2022. The Author(s).)

Background: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked recessive neurodegenerative disorder caused by mutations in the SLC16A2 gene that encodes thyroid hormone transporter. AHDS has been rarely reported in China., Case Presentation: This study reported a novel splicing mutation in the SLC16A2 gene in an 18-month-old male patient with AHDS. The patient was born to non-consanguineous, healthy parents of Chinese origin. He passed new-born screening for hypothyroidism, but failed to reach developmental milestones. He presented with hypotonia, severe mental retardation, dysarthria and ataxia. Genetic analysis identified a novel splicing mutation, NM&#95;006517.4: c.431-2 A > G, in the SLC16A2 gene inherited from his mother. The patient received Triac treatment, (triiodothyroacetic acid), a thyroid hormone analogue for 3 months. Triac treatment effectively reduced serum TSH concentrations and normalized serum T3 concentrations in the patient., Conclusions: This study reported the first case of AHDS treated by Triac in China. And the study expanded the mutational spectrum of the SLC16A2 gene in AHDS patients., (© 2022. The Author(s).)

Muscular atrophy after limb fracture is a frequently occurring complication with multiple causes. Different treatments and targeted rehabilitation procedures should be carried out based on the causes. However, bedside evaluation methods are invasive in clinical practice nowadays, lacking reliable non-invasive methods. In this study, we propose a non-invasive flexible surface electromyography system with machine learning algorithms to distinguish nerve-injury and limb immobilization-related atrophy. First, a flexible surface electromyography sensor was designed and verified by in vitro tests for its robustness and flexibility. Then, in vivo tests on rats proved the reliability compared with the traditional invasive diagnosis method. Finally, this system was applied for the diagnosis of muscular atrophy in 10 patients. The flexible surface electromyography sensor can achieve a max strain of 12.0%, which ensures close contact with the skin. The in vivo tests on rats show great comparability with the traditional invasive diagnosis method. It can achieve a high specificity of 95.28% and sensitivity of 98.98%. Application on patients reaches a relatively high specificity of 89.44% and sensitivity of 91.94%. The proposed painless surface electromyography system can be an easy and accurate supplementary for bedside muscular atrophy causes evaluation, holding excellent contact with the body.

Loss of skeletal muscle mass likely compromises performance and welfare in horses and thus routine monitoring would be valuable. Currently available methods to assess muscle mass require expert knowledge and are often expensive. To provide a simple method, a muscle atrophy scoring system (MASS) was created and tested by three evaluators (raters) in 38 horses of varying age, breed, and health status. Inter-rater agreement on atrophy scores was in the good-to-excellent range for ratings of the neck (ICC = 0.62), back (ICC = 0.62) and hind (ICC = 0.76) regions but was poor for the abdominal region (ICC = 0.29). Due to this low agreement, the abdominal region was excluded from further analysis. Associations between muscle atrophy scores and age, pituitary pars intermedia dysfunction (PPID) status, and body composition indicators, including weight and estimated fat-free mass (FFM), were examined. Weight was inversely associated with neck, back and hind muscle atrophy scores (β = -0.008, β = -0.008, β = -0.009, respectively; all P <0.001), but estimated FFM was not associated with muscle atrophy scores at any region (P >0.05). Age was positively related to neck (β = 0.030, P <0.01), back (β = 0.037, P <0.001) and hind (β = 0.040, P <0.001) muscle atrophy scores. PPID-positive horses (n = 4) had higher muscle atrophy scores than PPID-negative horses (n = 23), even after adjusting for age (P <0.05). This data suggests that neck, back and hind region evaluations by individual raters likely have acceptable reliability. In addition, these findings support further evaluation of the potential benefits of the MASS to identify and monitor muscle atrophy in horses., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To compare the one-year postoperative outcomes of anti-gravity treadmill rehabilitation with those of standard rehabilitation in patients with ankle or tibial plateau fractures., Design: An open-label prospective randomised study., Setting: Three trauma centres., Subjects: Patients were randomised into the intervention (anti-gravity treadmill) or control (standard protocol) rehabilitation group., Main Measures: The primary endpoint was changes in the Foot and Ankle Outcome Score for ankle fractures and Knee Injury and Osteoarthritis Outcome Score for tibial plateau fractures from baseline to 12 months after operation. Secondary endpoints were the subscores of these scores, muscle atrophy (leg circumference at 20 cm above and 10 cm below the knee joint) and the Dynamic Gait Index., Results: Initially, 73 patients (37 vs 36) underwent randomisation. After 12 months, 29 patients in the intervention group and 24 patients in the control group could be analysed. No significant difference was noted in the Foot and Ankle Outcome Score (80.8 ± 18.4 and 78.4 ± 21.1) and Knee Injury and Osteoarthritis Outcome Score (84.8 ± 15.2 and 81.7 ± 17.0). The change in the Dynamic Gait Index from 12 weeks to 12 months differed significantly between the groups ( P  = 0.04). Patients with tibial plateau fractures had a 3 cm wider thigh circumference in the intervention group than those in the control group (95% confidence interval: -0.2 to 6.3 cm, P  = 0.08)., Conclusion: One year after surgery, patients who had undergone anti-gravity treadmill rehabilitation showed better gait than patients in the control group, and those with tibial plateau fractures had less muscle atrophy.

Several chronic diseases lead to skeletal muscle loss and a decline in physical performance. MicroRNAs (miRNAs) are small, noncoding RNAs, which have exhibited their role in the development and diseased state of the skeletal muscle. miRNA regulates gene expression by binding to the 3' untranslated region of its target mRNA. Due to the robust stability in biological fluids, miRNAs are ideal candidate as biomarker. These miRNAs provide a novel avenue in strengthening our awareness and knowledge about the factors governing skeletal muscle functions such as development, growth, metabolism, differentiation, and cell proliferation. It also helps in understanding the therapeutic strategies in improving or conserving skeletal muscle health. This review outlines the evidence regarding the present knowledge on the role miRNA as a potential biomarker in skeletal muscle diseases and their exploration might be a unique and potential therapeutic strategy for various skeletal muscle disorders.

Heat shock protein family B member 8, encoded by HSPB8, is an essential component of the chaperone-assisted selective autophagy complex, which maintains muscle function by degrading damaged proteins in the cells. Mutations in HSPB8 have been reported to cause Charcot-Marie-Tooth type 2L, distal hereditary motor neuropathy IIa, and rimmed vacuolar myopathies (RVM). In this study, we identified a novel heterozygous frameshift variant c.525&#95;529del in HSPB8 in a large Japanese family with RVM, using whole exome sequencing. Three affected individuals had severe respiratory failure, which has not been addressed by previous studies. Muscle atrophy in the paraspinal muscles was also a clinical feature of the individuals affected with RVM in this study. The frameshift mutation was located in the last coding exon, and the mutated protein was predicted to harbor an isoleucine-leucine-valine (ILV) sequence, which corresponds to the IXI/V (isoleucine, X amino acids, and isoleucine or valine) motif. The IXI/V motif is essential for assembly into larger oligomers in other small heat shock proteins and all frameshift mutants of HSPB8 were predicted to share the ILV sequence in the C-terminal extension. The in silico prediction tools showed low protein solubility and increased aggregation propensity for the region around the ILV sequence. The IXI/V motif might be associated with the pathogenesis of HSPB8-related RVM., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Background : Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome. Patient and methods : We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking. Results : Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures. Conclusion : This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.

Allan-Herndon-Dudley is an X-linked recessive syndrome caused by pathogenic variants in the SLC16A2 gene. Clinical manifestations are a consequence of impaired thyroid metabolism and aberrant transport of thyroid hormones to the brain. Carrier females are generally asymptomatic and may show subtle symptoms of the disease. We describe a female with a complete Allan-Herndon-Dudley phenotype, carrying a de novo 543-kb deletion of the X chromosome. The deletion encompasses exon 1 of the SLC16A2 gene and JPX and FTX genes; it is known that the latter two genes participate in the X-inactivation process upregulating XIST gene expression. Subsequent studies in the patient demonstrated the preferential expression of the X chromosome with the JPX and FTX deletion., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sepsis and sepsis-induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell-based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo-like kinase 1 (PLK1) and phosphorylated protein kinase B (p-AKT) was decreased. Overexpression of PLK1 partly rescued LPS-induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS-induced atrophy in PLK1-overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1-AKT pathway. These findings enhance understanding of the mechanism of sepsis-induced skeletal muscle atrophy., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients., Methods: Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median)., Results: From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7-82.0) years], 44 died during the follow-up period of 23.7 (12.4-34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18-7.61; P = 0.02]., Conclusions: Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Monocarboxylate transporter 8 (MCT8) deficiency is an X-chromosome-linked neurodevelopmental disorder resulting from impaired thyroid hormone transport across the cell membrane. The diagnosis of MCT8 deficiency is typically delayed owing to the late appearance of signs and symptoms as well as the inability of standard biomarkers of neonatal screening to provide early detection. In this study, we report, for the first time, the ability to detect MCT8 deficiency at birth using dried blood spot (DBS) samples. Methods: We retrospectively measured triiodothyronine (T3), thyroxine (T4), and reverse T3 (rT3) levels in DBS samples obtained at 4-5 days of life from 6 infants with genetically confirmed MCT8 deficiency and from 110 controls. The latter consisted of 58 healthy term neonates obtained at the same time, 16 were stored for more than 1 year before measurement to match samples from the MCT8-deficient infants. Ten DBS samples were collected at day 1 of life and 42 samples were from prematurely born neonates. Measurements were carried out in extract from eight millimeters diameter DBS using liquid chromatography-tandem mass spectrometry. Results: Contrary to characteristic iodothyronine abnormalities of MCT8 deficiency during later life, T3 and T4 values were not discriminatory from those of other study groups. In contrast, rT3 was significantly lower. The T3/rT3 ratio was higher in the DBS samples from the MCT8-deficient infants compared with all other groups with no overlap ( p  < 0.0001). Conclusions: rT3 and T3/rT3 ratio in DBS samples obtained from neonates can serve as biomarkers to detect MCT8 deficiency at birth.

Background & Aims: Due to the lack of validated methods of muscle assessment, sarcopenia is not well described in critically ill children. The main objectives of this study were to assess muscle wasting using point-of-care ultrasound (POCUS) and anthropometry, as well as its association with nutrition delivery in PICU., Methods: This was a single-center, prospective cohort study, including consecutive children admitted to the PICU. Quadriceps femoris muscle thickness (QFMT) and anthropometrics measurements were performed at admission and then weekly until the 14th day of the PICU stay. The three moments of assessment were defined as T0 (baseline), T1 (7th day) and T2 (14th day). For analysis purposes, participants assessed only in T0 and T1 were defined as Subgroup 1, while those assessed in T0, T1 and T2 were defined as Subgroup 2. Actual total daily intake was determined by patient intake records until discharge or during the first 14 full days of PICU admission., Results: In all, 119 patients were included with a median age of 12.0 months (IQR 4.0-42.5). In Subgroup 1, QFMT significantly decreased between T0 and T1 (-12.93 ± 14.07 %; p < 0.001), and the same was observed in Subgroup 2 (-13.81 ± 13.05 %; p < 0.001). However, no differences in QFMT was observed between T1 and T2 (-2.06 ± 13.80 %; p = 0.936). Triceps skinfold thickness, mid-upper arm circumference, and upper arm muscle area presented a similar pattern of changes between periods in both groups. Decrease of QFMT at T1 was significantly correlated with the cumulative protein deficit in both subgroups, but not with the cumulative energy deficit., Conclusion: Substantial muscle wasting occurs early in critically ill children and may be related to insufficient protein delivery. Anthropometric measurements are valuable in PICU and POCUS has the potential to play a major role in sarcopenia assessment during critical illnesses., Trial Registration: Brazilian Clinical Trials registry, registration number: RBR-85YYGN., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Occupation ratio and fatty infiltration are important parameters for evaluating patients with rotator cuff tears. We analyzed the occupation ratio using a deep-learning framework and studied the fatty infiltration of the supraspinatus muscle using an automated region-based Otsu thresholding technique. To calculate the amount of fatty infiltration of the supraspinatus muscle using an automated region-based Otsu thresholding technique. The mean Dice similarity coefficient, accuracy, sensitivity, specificity, and relative area difference for the segmented lesion, measuring the similarity of clinician assessment and that of a deep neural network, were 0.97, 99.84, 96.89, 99.92, and 0.07, respectively, for the supraspinatus fossa and 0.94, 99.89, 93.34, 99.95, and 2.03, respectively, for the supraspinatus muscle. The fatty infiltration measure using the Otsu thresholding method significantly differed among the Goutallier grades (Grade 0; 0.06, Grade 1; 4.68, Grade 2; 20.10, Grade 3; 42.86, Grade 4; 55.79, p < 0.0001). The occupation ratio and fatty infiltration using Otsu thresholding demonstrated a moderate negative correlation (ρ = - 0.75, p < 0.0001). This study included 240 randomly selected patients who underwent shoulder magnetic resonance imaging (MRI) from January 2015 to December 2016. We used a fully convolutional deep-learning algorithm to quantitatively detect the fossa and muscle regions by measuring the occupation ratio of the supraspinatus muscle. Fatty infiltration was objectively evaluated using the Otsu thresholding method. The proposed convolutional neural network exhibited fast and accurate segmentation of the supraspinatus muscle and fossa from shoulder MRI, allowing automatic calculation of the occupation ratio. Quantitative evaluation using a modified Otsu thresholding method can be used to calculate the proportion of fatty infiltration in the supraspinatus muscle. We expect that this will improve the efficiency and objectivity of diagnoses by quantifying the index used for shoulder MRI., (© 2021. The Author(s).)

This study aims to determine clinically relevant phenotypic differences between the two most common phenotypic classifications in dysferlinopathy, limb girdle muscular dystrophy R2 (LGMDR2) and Miyoshi myopathy (MMD1). LGMDR2 and MMD1 are reported to involve different muscles, with LGMDR2 showing predominant limb girdle weakness and MMD1 showing predominant distal lower limb weakness. We used heatmaps, regression analysis and principle component analysis of functional and Magnetic Resonance Imaging data to perform a cross-sectional review of the pattern of muscle involvement in 168 patients from the Jain Foundation's international Clinical Outcomes Study for Dysferlinopathy. We demonstrated that there is no clinically relevant difference in proximal vs distal involvement between diagnosis. There is a continuum of distal involvement at any given degree of proximal involvement and patients do not fall into discrete distally or proximally affected groups. There appeared to be geographical preference for a particular diagnosis, with MMD1 being more common in Japan and LGMDR2 in Europe and the USA. We conclude that the dysferlinopathies do not form two distinct phenotypic groups and therefore should not be split into separate cohorts of LGMDR2 and MM for the purposes of clinical management, enrolment in clinical trials or access to subsequent treatments., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Muscle wasting, that is, reduction in muscle mass, is frequently observed in patients with chronic heart failure (CHF) and diabetes mellitus (DM)., Methods: We retrospectively examined 185 patients with CHF (median age of 71 years [interquartile range, 61-78 years]; 64% male) who received a dual-energy X-ray absorptiometry scan for assessment of appendicular skeletal muscle mass index (ASMI)., Results: Seventy patients with CHF (38%) had DM. Patients with DM had higher prevalences of ischemic heart disease and hypertension, lower levels of estimated glomerular filtration rate (eGFR) and ASMI, and higher levels of plasma renin activity (PRA) than did patients without DM. In simple regression analyses, ASMI was positively correlated with the Mini Nutritional Assessment Short Form (MNA-SF) score and levels of hemoglobin, eGFR, and fasting plasma insulin and was negatively correlated with levels of N-terminal pro B-type natriuretic peptide, PRA, and cortisol. In multiple linear regression analyses, age, MNA-SF score, DM, fasting plasma insulin level, and PRA were independently associated with ASMI. When multiple linear regression analyses were separately performed in a non-DM group and a DM group, MNA-SF score and fasting plasma insulin level were independent variables for ASMI in both groups. PRA was independently associated with ASMI in the DM group but not in the non-DM group, whereas cortisol concentration was independently associated with ASMI only in the non-DM group., Conclusions: In addition to malnutrition and reduction in plasma insulin, renin-angiotensin system activation may be responsible for the development of muscle wasting in CHF patients with DM., (© 2020 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Muscle atrophy is uncommon in myasthenia gravis. There are some reports in the literature of muscle atrophy in MUSK-positive myasthenia gravis. The authors present eight cases of AChR-positive myasthenia gravis associated with muscle atrophy. Symmetrical atrophy of the forearms with preserved hand muscles was identified in six cases and scapular winging in two cases. Atrophy appeared 3-18 years after the onset of myasthenia gravis and after a period of progression, the condition was stabilized. In all cases, there were no pain syndrome, no sensory loss, normal creatine phosphokinase (CPK) levels, no significant abnormality on MRI of the cervical spine. Concomitant neuropathies, amyotrophic lateral sclerosis and other neuromuscular diseases were excluded. All patients underwent quantitative electromyography and repetitive nerve stimulation. The authors suggest that the atrophy is not the sign of myasthenia gravis in this case and is caused by other neuromuscular diseases.

Background & Aims: Bioelectrical impedance analysis (BIA) and anthropometric predictive equations have been proposed to estimate whole-body (SMM) and appendicular skeletal muscle mass (ASM) as surrogate for dual energy X-ray absorptiometry (DXA) in distinct population groups. However, their accuracy in estimating body composition in non-dialysis dependent patients with chronic kidney disease (NDD-CKD) and kidney transplant recipients (KTR) is unknown. The aim of this study was to investigate the accuracy and reproducibility of BIA and anthropometric predictive equations in estimating SMM and ASM compared to DXA, in NDD-CKD patients and KTR., Methods: A cross-sectional study including adult NDD-CKD patients and KTR, with body mass index (BMI) ≥18.5 kg/m 2 . ASM and estimated SMM were evaluated by DXA, BIA (Janssen, Kyle and MacDonald equations) and anthropometry (Lee and Baumgartner equations). Low muscle mass (LowMM) was defined according to cutoffs proposed by guidelines for ASM, ASM/height 2 and ASM/BMI. The best performing equation as surrogate for DXA, considering both groups of studied patients, was defined based in the highest Lin's concordance correlation coefficient (CCC) value, the lowest Bland-Altman bias (<1.5 kg) combined with the narrowest upper and lower limits of agreement (LoA), and the highest Cohen's kappa values for the low muscle mass diagnosis., Results: Studied groups comprised NDD-CKD patients (n = 321: males = 55.1%; 65.4 ± 13.1 years; eGFR = 28.8 ± 12.7 ml/min) and KTR (n = 200: males = 57.7%; 47.5 ± 11.3 years; eGFR = 54.7 ± 20.7 ml/min). In both groups, the predictive equations presenting the best accuracy compared to DXA were SMM-BIA-Janssen (NDD-CKD patients: CCC = 0.88, 95%CI = 0.83-0.92; bias = 0.0 kg; KTR: CCC = 0.89, 95%CI = 0.86-0.92, bias = -1.2 kg) and ASM-BIA-Kyle (NDD-CKD patients: CCC = 0.87, 95%CI = 0.82-0.90, bias = 0.7 kg; KTR: CCC = 0.89, 95%CI = 0.86-0.92, bias = -0.8 kg). In NDD-CKD patients and KTR, LowMM frequency was similar according to ASM-BIA-Kyle versus ASM-DXA. The reproducibility and inter-agreement to diagnose LowMM using ASM/height 2 and ASM/BMI estimated by BIA-Kyle equation versus DXA was moderate (kappa: 0.41-0.60), in both groups. Whereas female patients showed higher inter-agreement (AUC>80%) when ASM/BMI index was used, male patients presented higher AUC (70-74%; slightly <80%) for ASM/height 2 index., Conclusions: The predictive equations with best performance to assess muscle mass in both NDD-CKD patients and KTR was SMM-BIA by Janssen and ASM-BIA by Kyle. The reproducibility to diagnose low muscle mass, comparing BIA with DXA, was high using ASM/BMI in females and ASM/height 2 in males in both groups., Competing Interests: Declaration of Competing Interest None declared., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Introduction: Extracellular matrix (ECM) gels have shown efficacy for the treatment of damaged tissues, most notably cardiac muscle. We hypothesized that the ECM gel prepared from skeletal muscle could be used as a treatment strategy for fatty shoulder cuff muscle degeneration., Methods: We conducted experiments to (1) evaluate host biocompatibility to ECM gel injection using a rat model and (2) examine the effect of ECM gel injection on muscle recovery after delayed repair of a released supraspinatus (SSP) tendon using a rabbit model., Results: The host biocompatibility to the ECM gel was characterized by a transient rise (first 2 weeks only) in several genes associated with macrophage infiltration, matrix deposition, and inflammatory cytokine production. By 8 weeks all genes had returned to baseline levels and no evidence of fibrosis or chronic inflammation was observed from histology. When gel injection was combined with SSP tendon repair, we observed a significant reduction (7%) in SSP muscle atrophy (24 + 3% reduction from uninjured) when compared with treatment with tendon repair only (31 + 7% reduction). Although fatty degeneration was elevated in both treatment groups, fat content trended lower (2%) in response to combined tendon repair and intramuscular ECM injection (4.1 + 2.1%) when compared with tendon repair only (6.1 + 2.9%). Transcriptome analysis revealed adipogenesis and osteoarthritis pathway activation in the repair only group. These key pathways were abrogated in response to treatment using combined repair plus gel., Discussion: The findings suggest that ECM injection had a modest but positive effect on muscle mass, fatty degeneration, and key cellular signaling pathways., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

We report a 74-year-old man with a 2-year history of proximal limb pain, body weight loss of 15 kg, and muscle weakness. Muscle atrophy was evident in the limbs and trunk, as well as the tongue. He was admitted to our hospital with suspected amyotrophic lateral sclerosis (ALS). Although he had no physical manifestations of Basedow disease such as palpitations, hyperhidrosis, hand tremor, exophthalmos, and an enlarged thyroid, he was diagnosed as having thyrotoxic myopathy as laboratory examinations indicated hyperthyroidism and positivity for TSH receptor antibody. The serum level of soluble IL-2 receptor was also elevated. Despite the severe muscle atrophy, the serum CK level was normal. A biopsy from the left quadriceps muscle revealed Type 1 fibers atrophy. Administration of anti-thyroid drugs normalized his thyroid function and the level of soluble IL-2 receptor, leading to improvement of the generalized muscle atrophy.

Skeletal muscle and the neuromuscular junction are the earliest sites to manifest pathological changes in amyotrophic lateral sclerosis (ALS). Based on prior studies, we have identified a molecular signature in muscle that develops early in ALS and parallels disease progression. This signature represents an intersection of signaling pathways including Smads, TGF-β, and vitamin D. Here, we show that the Wnt antagonist, Frizzled Related Protein (FRZB), was increased in ALS muscle samples and to a variable extent other denervating disease but only minimally in acquired myopathies. In the SOD1 G93A mouse, FRZB was upregulated in the early stages of disease (between 40 and 60 days) until end-stage. By immunohistochemistry, FRZB was predominantly localized to endomysial connective tissue and to a lesser extent muscle membrane. There was a significant increase in immunoreactivity surrounding atrophied myofibers. Because FRZB is a Wnt antagonist, we assessed β-catenin, the canonical transducer of Wnt signaling, and found increased levels mainly at the muscle membrane. In summary, we show that FRZB is part of a molecular signature of muscle denervation that may reflect disease progression in ALS. Our findings open up avenues for future investigation as to what roles FRZB and Wnt signaling might be playing in muscle denervation/reinnervation.

Rapidly identifying cachexia-inducing factors that directly induce muscle wasting is an existing challenge. We developed two reporter cell lines that allow swift detection of such factors in blood from patients. C2C12 myoblasts were used for the establishment of reporter cells. A luciferase reporter gene, driven by promoters of wasting genes, Muscle RING-finger protein-1 (MuRF1) and Muscle Atrophy F-Box Protein (MAFbx/Atrogin-1) were used for the construction of reporter constructs. Increased expression of these genes in muscle tissue under wasting conditions was shown in vivo and in vitro. We found these reporter cell lines could detect factors associated with cancer cachexia, such as myostatin (Mstn), activin A, and TNF-α. We further investigated the capacity to directly detect a cachectic state using plasma samples from cachectic mice and cancer patients. Activation of the reporter cell lines was observed by the addition of plasma from mice with cancer cachexia and serum samples from patients with pancreatic or colorectal cancer. These results indicate that the reporter cell lines are competent as a tool for screening cachexia-inducing factors and potentially distinguishing a cachectic state induced by cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Coronary artery bypass graft (CABG) surgery is known to induce significant muscle wasting. It remains to be investigated whether muscle wasting after CABG surgery relates to a worse clinical status at entry of rehabilitation and exercise-based rehabilitation remediates such muscle wasting. Design: Prospective observational study. Methods: In 21 males, changes in lean tissue mass (LTM) after CABG surgery were assessed and during a 12-week endurance exercise-based rehabilitation intervention. Changes in blood parameters and cardiopulmonary exercise capacity were assessed, and relations with changes in LTM were analysed. Results: LTM decreased by -1.9 ± 2.5 kg ( p  < .05) within 3 weeks after CABG surgery: greater LTM loss related to a lower ventilatory threshold at entry of rehabilitation ( r  = 0.58-0.61, p  < .05). LTM was fully restored (+2.1 ± 2.4 kg, p  < .05) during rehabilitation. Conclusion: In males, CABG-induced LTM reduction was associated with a worse aerobic exercise tolerance at entry of rehabilitation, but this LTM reduction was fully remediated by endurance exercise-based rehabilitation.

Background & Aims: Muscle wasting is highly prevalent in patients with chronic kidney disease (CKD). However, the assessment of skeletal muscle mass and strength in clinical settings is not commonly available. We aimed to evaluate the feasibility of serum creatinine/cystatin C (Cr/CysC) ratio in the assessment of muscle wasting., Methods: In 272 patients with CKD aged 66.5 ± 15.1 years, skeletal muscle mass and handgrip strength (HGS) were assessed. Skeletal muscle index (SMI) was calculated as skeletal muscle mass/height 2 . Low muscle mass was defined as SMI below the sex-specific 10th percentile of study population and low handgrip strength as less than 26 Kg for men and 18 Kg for women., Results: The Cr/CysC ratio was significantly lower in both the low SMI and low HGS groups. Moreover, the Cr/CysC ratio correlated with SMI (r = .306, p < .001) and HGS (r = .341, p < .001). After adjusting for confounding factors, age, sex, waist circumference, body fat mass, and Cr/CysC ratio were independently associated with SMI, whereas age, sex, diabetes, hemoglobin, estimated glomerular filtration rate, urine protein/creatinine ratio, SMI, and Cr/CysC ratio were independently associated with HGS., Conclusions: Cr/CysC ratio appears to be a promising surrogate marker for detecting muscle wasting in patients with CKD. Further studies are needed to extend our findings., Competing Interests: Conflict of Interest The authors declare no competing interests., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: To evaluate paraspinal back muscles of asymptomatic subjects using qualitative and quantitative analysis on CT and MRI and correlate the results with demographic data., Methods: Twenty-nine asymptomatic subjects were enrolled prospectively (age: mean 34.31, range 23-50; 14 men, 15 women) from August 2016 to April 2017. Qualitative analysis of muscles was done using Goutallier's system on CT and MRI. Quantitative analysis entailed cross sectional area (CSA) on CT and MRI, Hounsfield unit (HU) on CT, fat fraction using two-point Dixon technique on MRI. Three readers independently analyzed the images; intra- and inter-observer agreements were measured. Linear regression and Spearman's analyses were used for correlation with demographic data., Results: CSA values were significantly higher in men (p < 0.001). Fat fraction was higher (22.53% vs. 14.35%) and HU lower (36.00 vs. 47.43) in women (p < 0.001). Intra- and inter-observer reliabilities of the two methods were greater than 0.8, except for CSA of L5/S1 on MRI; however, regarding quantitative analysis, decreasing HU and increasing fat fraction were correlated with increasing age, female gender and lower lumbar segment (p < 0.001)., Conclusion: MRI and CT can be reliably used for qualitative and quantitative analysis of paraspinal back muscles, regarding fat content. Fat fraction and HU showed highest reliabilities.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its associated skeletal muscle wasting (SMW) and mortality. Currently, the relationships between PDAC, SMW, and survival are poorly understood. Thus, there is great need for a faithful small animal model with quantitative longitudinal outcome measures that recapitulate clinical PDAC, to define SMW onset and assess progression. Therefore, we aimed to validate dual energy X-ray absorptiometry (DEXA) as a longitudinal measure of lean mass, and demonstrate its utility to quantify SMW in the KCKO murine model of PDAC., Methods: In vivo body composition of: 1) untreated mice at 5, 8, 12, 18, and 22 weeks of age (n = 4) and 2) a cohort of mice with (n = 5) and without PDAC (n = 5), was determined via DEXA and lean mass of the lower hind limbs was predicted via a region of interest analysis by two-independent observers. Total body weight was determined. Tibialis anterior (TA) muscles were weighed and processed for histomorphometry immediately post-mortem. Statistical differences between groups were assessed using ANOVA and Student's t-tests. Linear regression models and correlation analysis were used to measure the association between TA and DEXA mass, and reproducibility of DEXA was quantified via the intraclass correlation coefficient (ICC)., Results: Lean mass in growing untreated mice determined by DEXA correlated with TA mass (r2 = 0.94; p <0.0001) and body weight (r2 = 0.89; p <0.0001). DEXA measurements were highly reproducible between observers (ICC = 0.95; 95% CI: 0.89-0.98). DEXA and TA mass also correlated in the PDAC cohort (r2 = 0.76; p <0.0001). Significant SMW in tumor-bearing mice was detected within 38 days of implantation, by DEXA, TA mass, and histomorphometry., Conclusions: DEXA is a longitudinal outcome measure of lean mass in mice. The KCKO syngeneic model is a bona fide model of PDAC associated SMW that can be quantified with longitudinal DEXA., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to elucidate the relationship between the quantitative value of suprapatellar effusion and the longitudinal changes in lower-extremity muscle mass (MM) in a cohort with knee osteoarthritis (KOA). Fifty-three subjects (106 legs) with bilateral radiographic KOA at baseline (BL) were enrolled. MM was calculated by bioimpedance analysis three times at BL, and at the one-year (1Y) and three-year (3Y) follow-ups. The longitudinal change in the lower-extremity MM was calculated by subtracting MM BL from MM 1Y , and MM 1Y from MM 3Y . Subjects with ≥1.0 z-score loss were defined as having severe MM loss (SMML). Effusion was evaluated as the sagittal area of suprapatellar pouch (mm 2 ) by ultrasonography. The ROC curve was drawn to determine the cut-off of effusion area. General estimating equations (GEEs) were conducted with the prevalence of SMML as the dependent variable and with the cut-off of effusion area as the independent variable. Sixteen legs (15.1%) demonstrated SMML BL-1Y and another sixteen legs demonstrated SMML 1Y-3Y . GEEs revealed that individuals with ≥90 mm 2 effusion had significantly higher odds of SMML BL-1Y prevalence (Odds ratio: 21.561; P-value: 0.003). Individuals with leachate knee effusion at BL had a significant risk of losing MM through the first year of the initial knee effusion assessment.

Purpose: The purpose of the study is to analyze the incidence, manifestations, and treatment of blepharoptosis caused by long-term use of corticosteroid eyedrops., Methods: Retrospective case series include 46 patients with a history of using corticosteroid eyedrops unilaterally for at least 2 months. The palpebral fissure, MRD1, and levator function were evaluated., Results: Among 46 patients, the differences of mean MRD1 (p < 0.0005), palpebral fissure height (p < 0.0005), and levator function (p = 0.003) between eyes with and without corticosteroid eyedrops application were significant. Ptosis existed in 40 out of 46 eyes with corticosteroid; the differences of the mean MRD1 (p < 0.0005) and palpebral fissure height (p = 0.001) between eyes with and without ptosis were significant. Nine patients underwent levator aponeurosis repair surgeries. Pathological examinations revealed mainly vascular fibers and few muscle fibers, as well as apoptosis of levator palpebrae muscle and Muller muscle., Conclusion: Blepharoptosis is frequently observed after chronic corticosteroid eyedrops use in Chinese population.

Rationale: This case report expands the mutation and phenotypic spectra of Beaulieu-Boycott-Innes syndrome (BBIS), and will be valuable for mutation-based pre- and post-natal screening of BBIS when conducting a genetic diagnosis., Patient Concerns: A 4-year old boy from Guilin City, Guangxi Zhuang Autonomous Region, China, was referred to our clinic for clarification of his diagnosis because he showed moderate intellectual disability., Diagnosis: Two novel compound heterozygous mutations of THOC6, c.664T>C (p.Trp222Arg) and c.945+1 G>A were identified in this patient by whole exome sequencing. The two mutations were evaluated as pathogenic and likely pathogenic respectively according to the American College of Medical Genetics guidelines. This is the first case displaying the BBIS phenotype reported in the Chinese population. These two mutations have not been reported previously., Interventions: Symptomatic treatment and rehabilitation training for patients., Outcomes: The genetic cause of the disease was identified. The family received scientific genetic counseling., Lessons: BBIS is a rare syndromic autosomal recessive disease with intellectual disability and it is normally difficult for clinicians to recognize it. Whole exome sequencing is an efficient way to identify the gene which causes a particular disease in patients.

Magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) were used to assess changes in thigh lean mass in septuagenarian men and women during a 5-year longitudinal study. Twenty-four older individuals participated in the study (10 men: 71.6 ± 4.1 years; 14 women: 71.3 ± 3.2 years at baseline). Thigh MRI and whole-body DXA scans were used to estimate changes in thigh lean mass. Both MRI and DXA showed that thigh lean mass was reduced by approximately 5% (P = 0.001) over the 5-year period in both men and women. The percentage loss of muscle mass determined with MRI and DXA showed moderate correlation (R 2  = 0.466; P < 0.001). Bland-Altman analysis showed that the average change over 5 years of follow-up measured by DXA was only 0.18% greater than MRI, where the limits of agreement between DXA and MRI were ± 10.4%. Baseline thigh lean mass did not predict the percentage loss of thigh lean mass over the 5-year period (R 2  = 0.003; P = 0.397), but a higher baseline body fat percentage was associated with a larger loss of thigh muscle mass in men (R 2  = 0.677; P < 0.003) but not in women (R 2  = 0.073; P < 0.176). In conclusion, (1) DXA and MRI showed a similar percentage loss of muscle mass over a 5-year period in septuagenarian men and women that (2) was independent of baseline muscle mass, but (3) increased with higher baseline body fat percentage in men.

Myopathies caused by MYH7 gene mutations are clinically and pathologically heterogeneous and, until recently, difficult to diagnose. The availability of NGS panels for hereditary neuromuscular diseases changed our insight regarding their frequency and allowed a better perception of the different phenotypes and morphological abnormalities associated. We present a male Portuguese patient with the classical phenotype of Laing early-onset distal myopathy (MPD1) beginning at 6 years of age, very slowly progressive, and with a mild to moderate impact on daily life by the age of 56. Muscle biopsy showed a myopathic pattern with hyaline bodies and cores. The NGS panel for structural myopathies identified a novel missense heterozygous variant, c.T4652C (p.Leu1551Pro), in the exon 34 of the MYH7 gene., (©2020 Gaetano Conte Academy - Mediterranean Society of Myology, Naples, Italy.)

We describe a 5-year-old male with developmental delay, behavioral problems, and dysmorphic features who was found by microarray to have a 93-kb duplication of uncertain significance that fully encompasses the third exon of CTNND2 (delta catenin). Mate-pair sequencing was used to determine that the duplication is tandem and is predicted to lead to CTNND2 haploinsufficiency. Haploinsufficiency for CTNND2 has been shown to result in developmental delay and intellectual disability, providing a unifying diagnosis for this patient. His features overlap those associated with the larger cri-du-chat deletion of this region, expanding the clinical phenotype of isolated CTNND2 variants. The use of mate-pair sequencing to determine the orientation of the small duplication was essential to the diagnosis and avoided the use of exome sequencing, which would not have defined the arrangement of the duplication. This is only the second reported patient, to our knowledge, with a single exon duplication of CTNND2., (© 2019 Wiley Periodicals, Inc.)

Primrose syndrome is a congenital malformation syndrome characterized by intellectual disability, developmental delay, progressive muscle wasting, and ear lobe calcification. Mutations in the ZBTB20 gene have been established as being accountable for this syndrome. In this study, a novel de novo ZBTB20 mutation, NM&#95;001164342.2:c.1945C>T (p.Leu649Phe), has been identified through whole exome sequencing (WES) in a female patient presenting a typical Primrose phenotype. Because the present patient exhibited recurrent otitis media, detailed immunological examinations were performed in this study and subnormal immunoglobulin levels were firstly identified in a Primrose patient. Anatomical anomaly of the inner ear has never been reported in this patient and WES data did not include any relevant variants causally linked with the immunologic defect. Thus, there is a possibility of a relation between an unclassified immunodeficiency with selective IgG2 deficiency and Primrose syndrome and this may be the reason of recurrent otitis media frequently observed in Primrose patients. Because subnormal levels of IgG2 in this patient might be caused by an unrelated and still uncharacterized genetic cause, further studies are required to prove the causal link between aberrant ZBTB20 function and immunodeficiency., (© 2019 Wiley Periodicals, Inc.)

Background: Posterior lumbar fusion is a widely accepted surgical technique; however, it has been related to the possibility of paraspinal muscle atrophy after surgery. We investigated 1-year postoperative changes in paraspinal muscle volume using a simple formula applicable to magnetic resonance imaging (MRI) or computed tomography (CT) images., Methods: Patients with degenerative lumbar spinal stenosis who underwent posterior interbody fusion (PLIF) at the L4/5 level in the period from May 2010 to June 2017 were enrolled in this study. Radiologic parameters were measured using MRI or CT images which were taken before surgery and at 1 year after surgery. The volume of the paraspinal muscles was calculated using a simple formula which was derived from the formula for calculating the volume of truncated elliptic cones., Results: A total of 40 patients were included; 24 were analyzed using MRI and 16 were analyzed using CT. The mean age of the patients was 59.6 ± 12.1 years and 32 (80.5%) were female. When comparing the preoperative and 1-year-postoperative images, multifidus muscle (MF) reduction was consistently observed in the MRI and CT groups, right and left (p = 0.003, p < 0.001, p = 0.005 and p < 0.001, respectively). In the erector spinae (ES) group, decrease in muscle volume was observed in the right-sided muscles of the CT group (p < 0.001), but no significant change was observed in the MRI group. The psoas muscle showed no significant change after 1 year. Conversely, regression analysis showed a negative correlation between MF muscle volume loss and age in the MRI group (right and left, p = 0.002 and p = 0.015, respectively), that is, the younger the age, the greater loss of muscle mass., Conclusion: After the posterior lumbar fusion, the volume of the MF muscles was markedly decreased, and the degree of decrease was apparent in the MRI. The volume of the ES muscles, which are located relatively laterally, also tended to decrease at 1 year after surgery.

This article highlights preclinical and clinical studies in the field of wasting disorders that were presented at the 12th Cachexia Conference held in Berlin, Germany, in December 2019. Herein, we summarize the biological and clinical significance of different strategies including antibodies that target Fn14, Spsb 1, SAA1 treatment, ZIP14, a MuRF1 inhibitor, and new diagnostic tools like T-cell communication targets and cut-offs for the detection of skeletal muscle wasting. Of particular interest were the transplantation of mesenchymal stromal cells and muscle stem cell communication. Importantly, one presentation discussed the effect of metal ion transporter ZIP14 loss that reduces cancer-induced cachexia. The potential of anti-ZIP14 antibodies and zinc chelation as anti-cachexia therapy may require testing in patients with cancer cachexia. Large clinical studies were presented such as RePOWER (observational study of patients with primary mitochondrial myopathy), MMPOWER (treatment with elamipretide in patients with primary mitochondrial myopathy), and ACT-ONE as well as new mouse models like the KPP mouse. Promising treatments include rapamycin analogue treatment, anamorelin, elanapril, glucocorticoids, SAA1, antibodies that target Fn14, and a MuRF1 inhibitor. Clinical studies investigated novel approaches, including the role of exercise. It remains a fact, however, that effective treatments for cachexia and wasting disorders are urgently needed in order to improve patients' quality of life and their survival., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Biallelic variants in Anoctamin 5 (ANO5) gene are causative of limb-girdle muscular dystrophy (LGMD) R12 anoctamin5-related, non-dysferlin Miyoshi-like distal myopathy (MMD3), and asymptomatic hyperCKemia., Objective: To describe clinic, histologic, genetic and imaging features, of ANO5 mutated patients., Methods: Five patients, four from France (P1, P2, P3 and P4) and one from Mexico (P5), from four families were included. P1 and P2, belonging to group 1, had normal muscle strength; Group 2, P3, P4 and P5, presented with muscular weakness. Muscle strength was measured by manual muscle testing, Medical Research Council (MRC) grades 1/5 to 5/5. Laboratory exams included serum CK levels, nerve conduction studies (NCS)/needle electromyography (EMG), pulmonary function tests, EKG and cardiac ultrasound. ANO5 molecular screening was performed with different approaches., Results: Group 1 patients showed myalgias with hyperCKemia or isolated hyperCKemia. Group 2 patients presented with limb-girdle or proximo-distal muscular weakness. Serum CK levels ranged from 897 to 5000 UI/L. Muscle biopsy analysis in P4 and P5 showed subsarcolemmal mitochondrial aggregates. Electron microscopy confirmed mitochondrial proliferation and revealed discontinuity of the sarcolemmal membrane. Muscle MRI showed asymmetrical fibro-fatty substitution predominant in the lower limbs.P1 and P2 were compound heterozygous for c.191dupA (p.Asn64Lysfs*15) and c.1898 + G>A; P3 was homozygous for the c.692G>T. (p.Gly231Val); P4 harbored a novel biallelic homozygous exons 1-7 ANO5 gene deletion, and P5 was homozygous for a c.172 C > T (p.(Arg 58 Trp)) ANO5 pathogenic variant., Conclusions: Our cohort confirms the wide clinical variability and enlarge the genetic spectrum of ANO5-related myopathies.