Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Activated Microglia Mediate the Motor Neuron-, Synaptic Denervation- and Muscle Wasting-Changes in Burn Injured Mice","authors":"Jingyuan Chen, Yoshinori Kitagawa, Fei Xie, Haobo Li, William R. Kem, Zerong You, Shingo Yasuhara, J. A. Jeevendra Martyn","doi":"10.1002/jcsm.13755","DOIUrl":"https://doi.org/10.1002/jcsm.13755","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle wasting (MW) of burn injury (BI) remains unresolved. Microglia-mediated inflammatory cytokine/chemokine release, motor neuron loss (MNL) and MW is observed after BI but connection of the central changes to synaptic-denervation and MW is unelucidated. Stimulation of microglia α7acetylcholine receptors (α7AChRs), a Chrna7gene-product, exhibits anti-inflammatory properties (decreased cytokine/chemokines). Hypothesis tested was that exploitation of the microglia α7AChR anti-inflammatory properties mitigates cytokine inflammatory responses, MNL, synaptic-denervation and MW of BI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wild-type or α7AChR knockout (A7KO) mice received 30% body BI or Sham BI (SB) under anaesthesia with and without selective α7AChR agonist, GTS-21. Lumbar spinal cord tissue and hindlimb muscles were harvested. Immunohistochemistry, TUNEL assay for apoptosis and/or Nissl staining were used to examine microglia (Iba1 staining), MNL (NeuN staining) and synapse morphology (synaptophysin for nerve and α-bungarotoxin for muscle α7AChR). Spinal cytokine/chemokine transcripts, inflammatory transducer-protein expression and tibialis, soleus and gastrocnemius muscle weights were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BI to Wild-type mice caused significant microgliosis (5.8-fold increase, <i>p</i> < 0.001) and upregulated TNF-α, IL-1β, CXCL2, MCP-1 transcripts, and inflammatory transducer-protein (STAT3 and NF-κB, <i>p</i> < 0.01) expression together with increased transcripts of iNOS (<i>p</i> < 0.01) and CD86 (<i>p</i> < 0.01) at day 14 reflective of inflammatory M1 microglia phenotype. Significant apoptosis, MNL (32.2% reduction, <i>p</i> < 0.05), increased spinal caspase-3 expression (> 1100-fold, <i>p</i> < 0.05) and synaptic denervation were observed with BI. The tibialis muscle endplates (synapse) of SB had a smooth pretzel shaped appearance with good apposition of presynaptic nerve to postsynaptic muscle. In BI mice, the normal pretzel-like appearance was lost, and the endplates were fragmented with less nerve to muscle apposition. Tibialis, soleus, and gastrocnemius mass were decreased 31.7% (<i>p</i> < 0.01), 23.4% (<i>p</i> < 0.01) and 27.5% (<i>p</i> < 0.01) relative to SB. The A7KO mice with SB showed significant MNL loss (61.5% reduction, <i>p</i> < 0.05), which was aggravated with BI, accompanied by significantly higher expression of STAT3 and Nf-kB (<i>p</i> < 0.05). GTS-21 ameliorated the spinal expression of above enumerated cytokines/chemokines, inflammatory transducer-proteins (<i>p</i> < 0.05) together with mitigated MNL","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Impact of Resistance Training and Chicken Intake on Vascular and Muscle Health in Elderly Women’ by Fujie et al.","authors":"Jiawei Du, Jinghua Hou","doi":"10.1002/jcsm.13768","DOIUrl":"https://doi.org/10.1002/jcsm.13768","url":null,"abstract":"<p>We carefully read the article by Fujie et al., titled ‘Impact of resistance training and chicken intake on vascular and muscle health in elderly women’ [<span>1</span>], published in the <i>Journal of Cachexia, Sarcopenia and Muscle</i>. The study investigated the effects of moderate-to-high-intensity resistance training combined with a high-protein diet (steamed chicken breast) on muscle mass, strength and arterial stiffness in elderly women. The findings suggest that high-protein intake significantly mitigates the resistance training-induced increase in arterial stiffness while further enhancing muscle health indicators, offering critical insights into clinical and public health implications. However, upon in-depth analysis, we believe that several key limitations in the study design, methodology, mechanistic exploration and statistical analysis may affect the reliability of the conclusions and their clinical translational value.</p><p>First, the study employed carotid-femoral pulse wave velocity (cfPWV) and carotid β-stiffness as the primary indicators of arterial stiffness, whereas muscle mass was assessed via ultrasound measurements of muscle thickness and echo intensity (EI). However, the descriptions of these measurement methods are entirely absent. For instance, the specific equipment used for cfPWV, the exact locations for signal acquisition and the standardized procedures for calculating time differences were not provided. Similarly, the ultrasound measurements of muscle thickness and EI lacked details on probe frequency, participant positioning and standardized protocols for repeated measurements. This lack of methodological detail may hinder the reproducibility of the study by other researchers and undermine the credibility and generalizability of the findings. We recommend supplementing the study with detailed descriptions of experimental procedures and referencing internationally recognized standards (e.g., guidelines from the European Society of Hypertension or the American Institute of Ultrasound in Medicine) to ensure transparency and reproducibility.</p><p>Second, the study did not assess the potential impact of high-protein intake on renal function (e.g., glomerular filtration rate [GFR]) or discuss the potential risks of long-term high-protein consumption, such as hyperuricemia or metabolic acidosis. Whereas high-protein diets have significant benefits for muscle health, long-term high-protein intake may impose additional renal burden, particularly in elderly populations with potentially declining renal function [<span>2</span>]. The nitrogenous waste produced by protein metabolism requires renal excretion, and prolonged high-protein intake may accelerate renal function decline. Studies have shown that high-protein diets may increase the risk of renal function deterioration in patients with chronic kidney disease (CKD) [<span>3</span>]. Additionally, high-protein diets may lead to metabolic acidosis, especially in the elder","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc Alleviates Diabetic Muscle Atrophy via Modulation of the SIRT1/FoxO1 Autophagy Pathway Through GPR39","authors":"Xing Yu, Xiaojun Chen, Weibin Wu, Huibin Tang, Yunyun Su, Guili Lian, Yujie Zhang, Liangdi Xie","doi":"10.1002/jcsm.13771","DOIUrl":"https://doi.org/10.1002/jcsm.13771","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle atrophy is a severe complication of diabetes, with autophagy playing a critical role in its progression. Zinc has been shown to alleviate hyperglycaemia and several diabetes-related complications, but its direct role in mediating diabetic muscle atrophy remains unclear. This study explores the potential role of zinc in the pathogenesis of diabetic muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vivo, C57BL/6J mice were induced with diabetes by streptozotocin (STZ) and treated with ZnSO₄ (25 mg/kg/day) for six weeks. Gastrocnemius muscles were collected for histological analysis, including transmission electron microscopy (TEM). Serum zinc levels were measured by ICP-MS. Protein expression was evaluated using immunofluorescence (IF), immunohistochemistry (IHC) and Western blotting (WB). Bioinformatics analysis was used to identify key genes associated with muscle atrophy. In vitro, a high-glucose-induced diabetic C2C12 cell model was established and received ZnSO₄, rapamycin, SRT1720, TC-G-1008, or GPR39-CRISPR Cas9 intervention. Autophagy was observed by TEM, and protein expression was assessed by IF and WB. Intracellular zinc concentrations were measured using fluorescence resonance energy transfer (FRET).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vivo, muscle atrophy, autophagy activation, and upregulation of SIRT1 and FoxO1, along with downregulation of GPR39, were confirmed in the T1D group. ZnSO₄ protected against muscle atrophy and inhibited autophagy (T1D + ZnSO₄ vs. T1D, all <i>p</i> < 0.0001), as evidenced by increased grip strength (212.40 ± 11.08 vs. 163.90 ± 10.95 gf), gastrocnemius muscle index (10.67 ± 0.44 vs. 8.80 ± 0.72 mg/g), muscle fibre cross-sectional area (978.20 ± 144.00 vs. 580.20 ± 103.30 μm<sup>2</sup>), and serum zinc levels (0.2335 ± 0.0227 vs. 0.1561 ± 0.0123 mg/L). ZnSO₄ down-regulated the expression of Atrogin-1 and MuRF1, and decreased the formation of autophagosomes in the gastrocnemius muscle of T1D mice (all <i>p</i> < 0.0001). RNA-seq analysis indicated activation of the SIRT1/FoxO1 signalling pathway in diabetic mice. ZnSO₄ down-regulated LC3B, SIRT1 and FoxO1, while upregulating P62 and GPR39 (all <i>p</i> < 0.05). In vitro, muscle atrophy, autophagy activation, and down-regulation of GPR39 were confirmed in the diabetic cell model (all <i>p</i> < 0.05). Both ZnSO₄ and TC-G-1008 down-regulated Atrogin-1, LC3B, SIRT1, and FoxO1, and up-regulated P62 and GPR39, inhibiting autophagy and improving muscle atrophy (all <i>p</i> < 0.05). The beneficial anti-atrophic effects of ZnSO₄ are diminished following treatment with SRT1720 or ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body Composition and Intradialytic Exercise in Kidney Disease: A Combined Analysis of the PEDAL and CYCLE-HD Randomised Controlled Trials","authors":"Khai Ping Ng, Jamie H. Macdonald, Robin Young, Daniel S. March, Matthew P. M. Graham-Brown, Thomas H. Mercer, Sharlene Greenwood, James O. Burton, Indranil Dasgupta","doi":"10.1002/jcsm.13748","DOIUrl":"https://doi.org/10.1002/jcsm.13748","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Haemodialysis patients are at high risk of myopenic obesity, necessitating effective nutritional status monitoring and intervention strategies. This combined analysis of two clinical trials (PEDAL trial and CYCLE-HD study) aimed to (i) determine the clinical utility of body mass index (BMI) in comparison to fat tissue index (FTI) and lean tissue index (LTI) and (ii) assess the effect of a 6-month intradialytic exercise intervention compared to usual care on FTI and LTI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A priori secondary endpoints in both trials included BMI, FTI and LTI. BMI was classified by World Health Organisation definitions (underweight, healthy, overweight or obese). FTI and LTI were determined by Bioelectrical Impedance Spectroscopy and classified by previous research evidence (FTI of 4–15 kg/m<sup>2</sup> and LTI of 15–20 kg/m<sup>2</sup> being associated with best survival). For aim (i), BMI was compared to FTI and LTI by correlation and classification. For aim (ii), changes over 6 months in FTI and LTI were compared between exercise intervention and control groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across both studies, 298 and 209 participants had bioelectrical impedance spectroscopy measurement at baseline and 6 months, respectively. Mean (SD) age: 58 (15) years; BMI: 28.2(6.3) kg/m<sup>2</sup>; male: 65%. At baseline, only 47 of 298 participants (16%) had an FTI and LTI associated with best survival. BMI correlated with FTI (r = 0.79; <i>p</i> < 0.0001). However, 34% of participants were misclassified by BMI (e.g., 9% of patients were classified as obese by BMI yet FTI revealed their body composition was healthy). BMI did not correlate with LTI (<i>p</i> = 0.15), and 86% of participants were misclassified by BMI (e.g., 73% of patients were classified as healthy, overweight or obese by BMI yet LTI revealed they were myopenic). There was no difference between exercise intervention and control groups in mean change (95% CI) over 6 months for LTI (−0.3 [−1.1 to 0.4] kg/m<sup>2</sup>; <i>p</i> = 0.4) or FTI (0.2 [−0.7 to 1.0] kg/m<sup>2</sup>; <i>p</i> = 0.7).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Worryingly, only a minority (16%) of haemodialysis patients had both LTI and FTI within the range associated with best survival. Body composition misclassification using conventional BMI cut-offs was common: despite having healthy, overweight or even obese BMI, the majority (73%) of patients had hidden myopenia according to LTI. Six months of intradialytic aerobic exe","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detrimental Effects of β2-Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research","authors":"Shibo Wei, So Jeong Park, Eunah Choi, Il-Young Jang, Yan Zhang, Yingqi Xue, Yunju Jo, Hee-Won Jung, Eunhye Ji, Jin Young Lee, Yujin Moon, Eunju Lee, Dongryeol Ryu, Beom-Jun Kim","doi":"10.1002/jcsm.13745","DOIUrl":"https://doi.org/10.1002/jcsm.13745","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>β2-Microglobulin (B2M) has garnered considerable interest as a potential pro-ageing factor, leading to speculation about its involvement in muscle metabolism and the development of sarcopenia, a key component of ageing phenotypes. To explore this hypothesis, we conducted a comprehensive investigation into the impact of B2M on cellular and animal muscle biology, as well as its clinical implications concerning sarcopenia parameters in older individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. For in vivo research, C57BL/6 mice aged 3 months were intraperitoneally given 250 μg of B2M daily, and muscular alterations were assessed one month later. Human blood samples were obtained from 158 participants who underwent assessments of muscle mass and function at an outpatient geriatric clinic affiliated with a teaching hospital. Sarcopenia and associated parameters were assessed using cut-off values specifically tailored for the Asian population. The concentration of serum B2M was quantified through an enzyme-linked immunosorbent assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Recombinant B2M inhibited in vitro myogenesis by increasing intracellular reactive oxygen species (ROS) production. Furthermore, B2M significantly induced differential myotube atrophy via ROS-mediated ITGB1 downregulation, leading to impaired activation of the FAK/AKT/ERK signalling cascade and enhanced nuclear translocation of FoxO transcription factors. Animal experiments showed that mice with systemic B2M treatment exhibited significantly smaller cross-sectional area of tibialis anterior and soleus muscle, weaker grip strength, shorter grid hanging time, and decreased latency time to fall off the rotating rod, compared to untreated controls. In a clinical study, serum B2M levels were inversely associated with grip strength, usual gait speed and short physical performance battery (SPPB) total score after adjustment for age, sex, and body mass index, whereas sarcopenia phenotype score showed a positive association. Consistently, higher serum B2M levels were associated with higher risk for weak grip strength, slow gait speed, low SPPB total score, and poor physical performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results provide experimental evidence that B2M exerted detrimental effects on muscle metabolism mainly by increasing oxidative stress. Furthermore, we made an effort to translate the results of in vitro and animal research into cl","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double-Blind Randomised Interventional Phase 2b Trial","authors":"Roger A. Fielding, Michael M. Dao, Kevin Cannon, Moise Desvarieux, Sam S. Miller, Michael Paul Gimness, Donald M. Brandon, Dennis T. Villareal, Olivier Bruyere, Ivan Bautmans, Kyle Rickner, Robert Perry, Stephen B. Kritchevsky, Nicolas Musi, Joe M. Chehade, Judith L. Kirstein, Evelien Gielen, Paul Pickrell, Pierre Dilda, Rene Lafont, Carole Margalef, Yves Rolland, Susanna Del Signore, Jean Mariani, Samuel Agus, Cendrine Tourette, Waly Dioh, Rob van Maanen, Stanislas Veillet","doi":"10.1002/jcsm.13750","DOIUrl":"https://doi.org/10.1002/jcsm.13750","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia is a progressive muscle disorder that may lead to mobility disability. No pharmaceutical interventions are currently available, and treatment relies on physical exercise and nutrition. The aim of SARA-INT was to investigate whether BIO101 (20-hydroxyecdysone), an activator of the MAS receptor, is safe and improves muscle function and physical performance of community dwelling older sarcopenic patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SARA-INT was a randomised three-arm interventional study (BIO101 175 mg bid /350 mg bid/placebo) with a planned 6-month treatment (up to 9 months in 50 subjects). Eligibility criteria for sarcopenia were meeting FNIH criteria for sarcopenia and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary endpoint was the change from baseline (CFB) in gait speed (GS) measured by 400-m walking test (400MWT), secondary endpoints being CFB in other physical performance tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 233 participants were randomised (mean age 75.5 ± 7.12; 54.3% female), of whom 232 and 156 were included in the full analysis set (FAS) and per-protocol (PP) populations, respectively. Due to COVID-19 pandemic, 55% of on-site end-of-treatment efficacy assessments were lost, reducing the studies' power. In the primary analysis (mix of 6/9 months), BIO101 350 mg bid treatment after 6/9 months was associated with an improvement in the 400MWT of 0.07 m/s versus placebo in the FAS population (not significant) and of 0.09 m/s in the PP population (<i>p</i> = 0.008). BIO101 350 mg bid treatment effect on the 400MWT GS was also observed in pre-defined subpopulations at higher risk of mobility disability (0.0474 m/s for slow walkers, 0.0521 m/s for obese and 0.0662 m/s for chair stand sub-score ≤ 2 from SPPB in the FAS population), with a trend for a dose response. BIO101 showed a good safety profile at both doses (number of subjects with related treatment emergent adverse events (TEAEs) of 13 (16.0%), 10 (13.3%) and 10 (13.5%) in the placebo, 175 mg and 350 mg BIO101 groups, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>After 6 to 9 months of treatment, BIO101 350 mg bid showed strong trends consistent with a clinically relevant effect on the 400MWT GS, close to the minimal clinically important difference (MCID) in sarcopenia (0.1 m/s). This was also shown in predefined subpopulations at higher risk of mobility disability. BIO101 showed a good safety profile. Taken together, efficacy a","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning Technique for Automatic Segmentation of Proximal Hip Musculoskeletal Tissues From CT Scan Images: A MrOS Study","authors":"Mahdi Imani, Jared Buratto, Thang Dao, Erik Meijering, Sara Vogrin, Timothy C. Y. Kwok, Eric S. Orwoll, Peggy M. Cawthon, Gustavo Duque","doi":"10.1002/jcsm.13728","DOIUrl":"https://doi.org/10.1002/jcsm.13728","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related conditions, such as osteoporosis and sarcopenia, alongside chronic diseases, can result in significant musculoskeletal tissue loss. This impacts individuals' quality of life and increases risk of falls and fractures. Computed tomography (CT) has been widely used for assessing musculoskeletal tissues. Although automatic techniques have been investigated for segmenting tissues in the abdomen and mid-thigh regions, studies in proximal hip remain limited. This study aims to develop a deep learning technique for segmentation and quantification of musculoskeletal tissues in CT scans of proximal hip.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined 300 participants (men, 73 ± 6 years) from two cohorts of the Osteoporotic Fractures in Men Study (MrOS). We manually segmented cortical bone, trabecular bone, marrow adipose tissue (MAT), haematopoietic bone marrow (HBM), muscle, intermuscular adipose tissue (IMAT) and subcutaneous adipose tissue (SAT) from CT scan images at the proximal hip level. Using these data, we trained a U-Net–like deep learning model for automatic segmentation. The association between model-generated quantitative results and outcome variables such as grip strength, chair sit-to-stand time, walking speed, femoral neck and spine bone mineral density (BMD), and total lean mass was calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An average Dice similarity coefficient (DSC) above 90% was observed across all tissue types in the test dataset. Grip strength showed positive correlations with cortical bone area (coefficient: 0.95, 95% confidence interval: [0.10, 1.80]), muscle area (0.41, [0.19, 0.64]) and average Hounsfield unit for muscle adjusted for height squared (AHU/h<sup>2</sup>) (1.1, [0.53, 1.67]), while it was negatively correlated with IMAT (−1.45, [−2.21, −0.70]) and SAT (−0.32, [−0.50, −0.13]). Gait speed was directly related to muscle area (0.01, [0.00, 0.02]) and inversely to IMAT (−0.04, [−0.07, −0.01]), while chair sit-to-stand time was associated with muscle area (0.98, [0.98, 0.99]), IMAT area (1.04, [1.01, 1.07]), SAT area (1.01, [1.01, 1.02]) and AHU/h<sup>2</sup> for muscle (0.97, [0.95, 0.99]). MAT area showed a potential link to non-trauma fractures post-50 years (1.67, [0.98, 2.83]). Femoral neck BMD was associated with cortical bone (0.09, [0.08, 0.10]), MAT (−0.11, [−0.13, −0.10]), MAT adjusted for total bone marrow area (−0.06, [−0.07, −0.05]) and AHU/h<sup>2</sup> for muscle (0.01, [0.00, 0.02]). Total spine BMD showed similar associations and with AHU for muscle (0.02, [0.00, 0.05]). Total lean mass was correlated with cortical bone (517.3, [148","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Growth Differentiation Factor 15 (GDF15) in Paediatric Disease: A Systematic Review","authors":"David W. Kronenberger, Teresa A. Zimmers, Rick K. Ralston, Daniel V. Runco","doi":"10.1002/jcsm.13712","DOIUrl":"10.1002/jcsm.13712","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Growth Differentiation Factor 15 (GDF15), a nonspecific inflammatory marker and member of the TGF-β superfamily, has a well-established role in both inflammation and metabolic modulation, but lacks a comprehensive paediatric literature review. In several adult disease states, including cancer cachexia and pregnancy, circulation and expression of GDF15 has been of clinical and scientific interest, but little published paediatric data exists. As such, we aim to summarize existing paediatric studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review follows the PRISMA-ScR guidelines for reporting and aims to summarize existing paediatric studies including GDF15, describe disease entities in which GDF15 has been investigated including existing reference ranges, and identify literature gaps to present future clinical and research direction. Our search strategy queried Ovid MEDLINE, Ovid Embase, Cochrane Library and Scopus databases to find original scientific articles measuring GDF15 from birth through children up to age 18. Data relating to study participant demographic and disease pathology, GDF15 measurement methods and clinical outcomes of interest were extracted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-two studies were included, classified as cardiac, endocrine, mitochondrial, hematologic, neonatal, oncologic, infectious, rheumatologic, renal, neurologic or healthy. While several entities demonstrated elevated GDF15, the highest median GDF15 levels were observed in cardiac arrest 7089 pg/mL (interquartile range 3805–13 306) and mitochondrial diseases 4640 pg/mL (1896–14 064). In certain conditions, including cardiac stress, polycystic ovarian syndrome (PCOS), Kawasaki Disease (KD) and certain mitochondrial myopathies GDF15 can normalize with disease treatment or resolution. Of healthy children studied, GDF15 levels were highest in healthy neonates and followed a predictable pattern, decreasing over time. Mean and standard deviation values of GDF15 in healthy children were 343.8 ± 221.0 pg/mL, with a range of 90–1134 pg/mL for study averages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Circulating GDF15 has been studied in a variety of paediatric diseases. However, variable evaluated outcome measures and GDF15 measurement methodologies prevent generalizability and direct comparison of these published studies. Validating normal GDF15 levels in children with standardized and reproducible methodology will help clarify GDF15's utility as a diagnostic marker of disease, a necessary step to","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicomponent Interventions for Adults With Cancer Cachexia: A Systematic Review","authors":"Megan Bowers, Carmine Petrasso, Amy McLuskie, Joanne Bayly, Barry J. A. Laird, Irene J. Higginson, Matthew Maddocks","doi":"10.1002/jcsm.13716","DOIUrl":"https://doi.org/10.1002/jcsm.13716","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia has substantial impacts on people's quality of life. There is no current gold standard treatment, but the complex pathophysiology of cachexia suggests that a multitargeted and individualised treatment approach is needed. We aimed to evaluate the extent to which multicomponent interventions have targeted the key features of cachexia and been tailored to individuals, and differential effects on quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic review of multicomponent interventions for adults with cancer cachexia. We searched four databases, two clinical trial registers and MedRxiv on 20 June 2024. Intervention components were classified by intervention category (nutritional, exercise/physical activity, pharmacological and psychosocial), cachexia feature(s) targeted (reduced energy intake, altered metabolism, involuntary weight loss and decline in physical function) and level of tailoring. Within-arm standardised mean changes in quality of life over time, as well as standardised mean differences between study arms, were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-two multicomponent interventions were included, of which two combined components from all four intervention categories, and nine targeted all four key features of cachexia. Eighteen multicomponent interventions were fully tailored and 30 were partly tailored to individuals. Within-arm standardised mean changes in quality of life were calculated for thirteen studies; all had a high risk of bias or raised concerns. In eleven studies, quality of life scores improved following the intervention, whereas in two studies they declined. Standardised mean differences between study arms were calculated for four studies; in three, the intervention arm showed a greater improvement in quality of life scores than the usual care arm. Amongst these data, there was no indication that the number of cachexia features targeted, or the extent of tailoring, was associated with a greater improvement in quality of life scores; however, the heterogeneity prevented us from concluding on our hypothesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review mapped out in detail the combinations of intervention categories used, the key features of cachexia targeted, and the extent of tailoring across multicomponent interventions for adults with cancer cachexia. Only a small proportion of the multicomponent interventions targeted all four key features of cachexia, but most were either partly or fully ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Carbohydrate Diet Exacerbates Denervation-Induced Atrophy of Rat Skeletal Muscle Under the Condition of Identical Protein Intake","authors":"Aki Yokogawa,&nbsp;Kohei Kido,&nbsp;Ikuru Miura,&nbsp;Eisuke Oyama,&nbsp;Daisuke Takakura,&nbsp;Keigo Tanaka,&nbsp;Daniel J. Wilkinson,&nbsp;Kenneth Smith,&nbsp;Philip J. Atherton,&nbsp;Kentaro Kawanaka","doi":"10.1002/jcsm.13738","DOIUrl":"https://doi.org/10.1002/jcsm.13738","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>While decreased protein intake is associated with muscle mass loss, it is unclear whether a decrease in carbohydrate intake adversely affects muscle atrophy independently of protein intake. Herein, we examined whether a low-carbohydrate (low-CHO) diet exacerbates denervation-induced muscle atrophy under conditions of identical protein intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>On day one of the experiment, male Wistar rats underwent unilateral denervation. The contralateral leg was used as the control. After denervation, rats were divided into two dietary groups: high-carbohydrate (high-CHO) and low-CHO. Each group was fed a high-CHO (70% carbohydrate) or low-CHO (20% carbohydrate) diet over 7 days. Total protein and energy intakes in both groups were matched by pair feeding. Rats were provided with deuterium oxide (D₂O) tracer over the last 3 days of dietary intervention to quantify myofibrillar (muscle) protein synthesis (MPS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Denervation reduced wet weight of the gastrocnemius muscle compared to the contralateral control (<i>p</i> &lt; 0.05). Reductions in gastrocnemius muscle weight were greater in the low-CHO group (−34%) than the high-CHO group (−28%) (<i>p</i> &lt; 0.05). Although denervation decreased MPS compared to the contralateral control (<i>p</i> &lt; 0.05), no dietary effect on MPS was observed. Denervation resulted in increased mRNA and protein expression of Atrogin-1, a ubiquitin E3 ligase, compared to that in the contralateral control (<i>p</i> &lt; 0.05). Increases in Atrogin-1 gene and protein expression due to denervation were greater in the low-CHO group than in the high-CHO group (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We conclude that a low-CHO diet may exacerbate denervation-induced atrophy in fast-twitch-dominant muscles compared to a high-CHO diet, even when the same protein intake is maintained. Although blunted MPS contributed to muscle atrophy due to denervation, exacerbation of muscle atrophy by the low-CHO diet was not accompanied by explanatory changes in MPS. The effect of the low-CHO diet might be related to promotion of muscle-specific ubiquitin E3 ligase gene expression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}