Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Correction to ‘Determination of Ultrasound Reference Values for Diagnosing Low Muscle Mass in Older Chinese Adults’","authors":"","doi":"10.1002/jcsm.70224","DOIUrl":"10.1002/jcsm.70224","url":null,"abstract":"<p>\u0000 <span>S. Li</span>, <span>K. Xu</span>, <span>A. Wang</span>, et al., “ <span>Determination of Ultrasound Reference Values for Diagnosing Low Muscle Mass in Older Chinese Adults</span>,” <i>Journal of Cachexia, Sarcopenia and Muscle</i> <span>16</span>, no. <span>6</span> (<span>2025</span>): e70155, https://doi.org/10.1002/jcsm.70155.\u0000 </p><p>In the ‘Author List’ section, the fourth author's name was incorrectly listed as ‘Chenfan Qin’. This should have read: ‘Chengfan Qin’ and has now been corrected in the article.</p><p>We apologize for this error.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215786","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":"Cancer Cachexia Prevalence Is Underestimated in Medical Records of Patients in a Regional Tertiary Hospital","authors":"Yann Colardelle,&nbsp;Melanie Daligault,&nbsp;Julien Grosjean,&nbsp;Stefan J. Darmoni,&nbsp;Badisse Dahamna,&nbsp;Richard B. Weiskopf,&nbsp;Vickie E. Baracos","doi":"10.1002/jcsm.70225","DOIUrl":"10.1002/jcsm.70225","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Widespread lack of awareness and limited real-world prevalence evidence have impeded cachexia care and research. We hypothesized that healthcare professionals may identify the term cachexia, leading to International Classification of Diseases (ICD) coding for this term, with or without records of body weight loss for diagnosing cancer cachexia, and that frequently, ICD coding does not accurately reflect weight data.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We assessed cachexia prevalence in patients diagnosed with cancer, using the Clinical Data Warehouse of a French hospital containing two types of real-world digitized data: (a) ‘structured’: coded diagnoses and electronic records; (b) ‘unstructured’: uncoded clinical narratives/reports: discharge summaries, procedure results, letters. Two sequential searches covering 2018–2023 (1) determined the prevalence of cachexia in all patients with a diagnosis of cancer using ICD-10 code R64 (cachexia), electronic records of body weight and unstructured narrative data; and (2) examined data of cancers of high-prevalence cachexia: colorectal, pancreatic and bronchial/lung cancers, determining (a) prevalence of cachexia by these criteria; (b) extent to which a diagnosis of cachexia was supported by weight loss data; and (c) extent to which the diagnosis of cachexia was not made despite objective weight data indicating its presence.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 76 547 of 737 906 patients had cancer of any primary type; 1856 (2.42%) of these had a cachexia diagnosis: 620 identified by ICD code, 1507 by unstructured data, including 271 by both. Of 6946 patients with colorectal, pancreatic or bronchial/lung cancer, 2033 patients (29.3%) were identified with cachexia by structured and/or unstructured data; both approaches were required to discover cachexia cases. From structured data an ICD-R64 search found only 254 patients described by the term cachexia, of which 127 had weight data supporting the diagnosis in the electronic medical record. An additional 1340 patients with BMI &lt; 20 kg/m&lt;sup&gt;2&lt;/sup&gt; or weight loss &gt; 5% were not coded as cachectic. Unstructured data for the three cancers identified 439 additional cachexic patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;(1) Standard ICD code-searching underestimated cachexia prevalence in all patients and those with high-prevalence-cachexia cancers; (2) Many cachexia cases were not diagnosed, although data indicated its presence; (3) Many cachexia cases diagnosed by judgemen","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211550","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":"Physical Fitness and Physical Function in Patients With Fabry Disease: A Cross-Sectional Multicentre Study","authors":"Nicola Vitturi,&nbsp;Giorgia Gugelmo,&nbsp;Andrea Gasperetti,&nbsp;Federica Duregon,&nbsp;Alessandro Dalmonico,&nbsp;Livia Lenzini,&nbsp;Sara Sponchiado,&nbsp;Gianni Carraro,&nbsp;Giacomo Marchi,&nbsp;Mattia Cominacini,&nbsp;Claudia Momentè,&nbsp;Federica Baciga,&nbsp;Claudia Baschirotto,&nbsp;Federica Caccia,&nbsp;Domenico Girelli,&nbsp;Andrea Ermolao,&nbsp;Gian Paolo Fadini,&nbsp;Yuri Battaglia","doi":"10.1002/jcsm.70233","DOIUrl":"10.1002/jcsm.70233","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting multiple organs, including the musculoskeletal system. The physical status of FD patients remains poorly characterized. This multicentre cross-sectional study aimed to evaluate physical fitness and function in FD patients and investigate associations with sex, FD phenotype and treatment status.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Adults (aged ≥ 18 years) with genetically confirmed FD were recruited. Demographic and laboratory data were collected. Physical fitness was assessed using cardiopulmonary exercise testing (VO&lt;sub&gt;2&lt;/sub&gt; peak) and body composition parameters (fat-free mass index [FFMI], fat mass index [FM] and phase angle [PA]) via bioelectrical impedance analysis. Physical function was evaluated with performance tests (6-min walk test, handgrip strength test, 30-s chair-stand test, short physical performance battery), muscle strength tests (isometric and isokinetic knee strength) and self-report fatigue questionnaires. Statistical analyses were stratified by sex, phenotype (classic vs. late-onset/Variants of Uncertain Significance [VUS]) and treatment status (enzyme replacement therapy [ERT]/chaperone-treated versus untreated).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Forty-two FD patients (13 males; mean age 46 ± 13.9 years) were enrolled. VO&lt;sub&gt;2&lt;/sub&gt; &lt; 85% of predicted was more frequent in classic phenotype patients (53.8%) than in late-onset/VUS (11.5%; &lt;i&gt;p&lt;/i&gt; &lt; 0.01). FFMI was lower in classic than late-onset/VUS (16.8 ± 1.0 vs. 18.6 ± 2.1 kg/m&lt;sup&gt;2&lt;/sup&gt;; &lt;i&gt;p&lt;/i&gt; = 0.01). Treated males had lower PA than untreated males (4.8° ± 1.0° vs. 7.6° ± 0.9°; &lt;i&gt;p&lt;/i&gt; = 0.04), and PA correlated with VO&lt;sub&gt;2&lt;/sub&gt; peak (&lt;i&gt;r&lt;/i&gt; = 0.879; &lt;i&gt;p&lt;/i&gt; = 0.01). Among classic phenotype males, 74.3% scored below the 50th percentile in handgrip strength (26.1 ± 7.8 kg), and 60.9% performed below predicted values in the 30-s chair-stand test (12.4 ± 4.3 repetitions). Self-reported fatigue scores were higher in classic versus late-onset/VUS patients (&lt;i&gt;p&lt;/i&gt; = 0.05) and in treated patients compared to untreated patients (&lt;i&gt;p&lt;/i&gt; = 0.02).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Classic FD phenotype, particularly in males, was associated with reduced exercise capacity, muscle mass and physical performance. These findings support the integration of cardiopulmonary exercise testing, physical functional assessments and body composition analysis into the routine evaluation of FD patients.&lt;/p&gt;\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215788","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 ‘Muscle-Specific Strength Better Predicts Physical Performance Decline Than Conventional Metrics: The I-Lan Longitudinal Aging Study’ by Chien et al.—The Authors Reply","authors":"Wei-Ju Lee,&nbsp;Wen-Kai Chien,&nbsp;Liang-Kung Chen","doi":"10.1002/jcsm.70238","DOIUrl":"10.1002/jcsm.70238","url":null,"abstract":"&lt;p&gt;We thank Dr. Lima and Dr. Blazevich for their insightful comments on our recently published work, “Muscle-Specific Strength Better Predicts Physical Performance Decline Than Conventional Metrics: The I-Lan Longitudinal Aging Study.” [&lt;span&gt;1&lt;/span&gt;] Their observations regarding the paradoxical characteristics of individuals with low muscle-specific strength (MSS), the influence of adiposity on strength interpretation and the potential role of relative handgrip strength (rHGS) raise important considerations for advancing the assessment of muscle function.&lt;/p&gt;&lt;p&gt;As the commenters noted, participants with low MSS have higher skeletal muscle index despite lower absolute grip strength, suggesting a phenotype marked by elevated adiposity and reduced contractile efficiency. They further proposed that grip strength normalized to body mass may better capture functional demands during daily activities, consistent with evidence linking rHGS to cardiometabolic and physical outcomes [&lt;span&gt;2, 3&lt;/span&gt;]. These perspectives align with evolving consensus in the field. The Asian Working Group for Sarcopenia (AWGS) 2025 Consensus supports the concept that muscle-specific strength is emerging as a more sensitive indicator of muscle function than absolute strength or muscle mass alone [&lt;span&gt;4&lt;/span&gt;]. Similarly, the Global Leadership Initiative on Sarcopenia (GLIS) recommends the use of either muscle strength or muscle-specific strength as the primary functional component in sarcopenia assessment, while acknowledging that MSS remains under methodological refinement and requires further empirical validation [&lt;span&gt;5&lt;/span&gt;]. Given that individuals with low MSS in our cohort also demonstrated higher adiposity, these observations are highly relevant to growing discussions about muscle quality, efficiency and sarcopenic obesity.&lt;/p&gt;&lt;p&gt;To address the scientific questions raised, we conducted supplemental analyses within the ILAS cohort comparing MSS with three forms of rHGS—normalized to body weight, body mass index (BMI) or height&lt;sup&gt;2&lt;/sup&gt;—in predicting physical decline [&lt;span&gt;3&lt;/span&gt;]. This analysis used the same participants and baseline measurements as described in our original publication [&lt;span&gt;1&lt;/span&gt;]. MSS was calculated as handgrip strength divided by dominant-hand lean mass, with low MSS defined as the lowest age- and sex-specific quintile. In parallel, rHGS metrics were constructed using the same quintile-based classification. Although the commenters suggested applying The Sarcopenia Definition and Outcomes Consortium (SDOC) rHGS cutoffs, we did not adopt these thresholds because they were developed in Western populations using different measurement modalities. The primary outcome was impaired physical performance at follow-up, defined as a five-time chair stand time ≥ 12 s [&lt;span&gt;6&lt;/span&gt;]. Multivariable logistic regression models, adjusted for demographic, cognitive, functional and comorbidity covariates used in the original study, were applied to e","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215787","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":"Menopause, Female Sex Hormones, Skeletal Muscle Mass and Muscle Protein Turnover in Humans","authors":"Campbell Menzies,&nbsp;Richard Bowtell,&nbsp;Natalie Shur,&nbsp;Matthew S. Brook","doi":"10.1002/jcsm.70232","DOIUrl":"10.1002/jcsm.70232","url":null,"abstract":"<p>Sarcopenia describes the loss of muscle mass and function with age. The increase in prevalence of sarcopenia in women appears to coincide with the onset of menopause, which is characterized by large changes to the hormonal milieu such as decreased oestrogen and progesterone concentrations. Although the timing of menopause and sarcopenia may coincide, there is a lack of high-quality evidence demonstrating a link between the two. This narrative review aims to assess evidence for the effects of menopause on muscle mass and muscle protein turnover. Longitudinal (<i>n</i> = 4/5) and cross-sectional (<i>n</i> = 7/11) studies demonstrate a reduction in lean or muscle mass across the menopausal transition with −2.5% and −5.7% reductions in perimenopausal and postmenopausal women, respectively, compared to premenopausal women. Most of this evidence (<i>n</i> = 10/11) is taken through assessment of lean body mass via dual-energy x-ray absorptiometry (DXA), which may underestimate changes in muscle mass. Assessment on changes to muscle protein turnover is largely limited to short-term measures of muscle protein synthesis (MPS), which may be elevated in older women versus younger women (<i>n</i> = 3/7) or age-matched males (<i>n</i> = 4/5). MPS responses to anabolic stimuli, such as resistance exercise (<i>n</i> = 3/4) or protein ingestion (<i>n</i> = 3/6), may be blunted in older women. Evidence assessing muscle protein breakdown (MPB) is lacking; however, evidence from animal and cell models demonstrates the role of estradiol in suppressing MPB, which may contribute to an increase in MPB following menopause. Advancements in understanding the role of the menopausal transition in the regulation of muscle mass, and subsequent effectiveness of interventions such as exercise or exogenous hormone provision will enable healthy ageing and sarcopenia prevention in older women.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215791","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":"Single-Cell RNAseq Identifies Heterogeneity in Myoblasts From Older Adults With Differences Related to Muscle Mass and Function","authors":"Mark A. Burton,&nbsp;Emma S. Garratt,&nbsp;Hanan Y. Sharkh,&nbsp;Matthew O. Hewitt,&nbsp;Elie Antoun,&nbsp;Leo D. Westbury,&nbsp;Elaine M. Dennison,&nbsp;Nicholas C. Harvey,&nbsp;Cyrus Cooper,&nbsp;Harnish P. Patel,&nbsp;Keith M. Godfrey,&nbsp;Karen A. Lillycrop","doi":"10.1002/jcsm.70213","DOIUrl":"10.1002/jcsm.70213","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Ageing is associated with the loss of muscle mass and function, with consequences for metabolic health, frailty and independence in later life. The aim of this study was to investigate the transcriptional heterogeneity of human proliferating muscle satellite/stem cells (myoblasts) from older adults and how this heterogeneity may vary between healthy individuals and those with low muscle mass and function.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Single-cell transcriptomic analysis was carried out on proliferating myoblasts isolated from &lt;i&gt;vastus lateralis&lt;/i&gt; biopsies from 132 participants (34 male, 98 female) aged 72–83 years from the Hertfordshire Sarcopenia Study extension. Uniform Manifold Approximation and Projection (UMAP) clustering was applied to identify clusters of myoblasts with distinct transcriptional profiles, Gene Ontology analysis was used to identify pathways enriched among the clusters, and pseudotime trajectory analysis was used to identify inferred cell lineages. Differential gene expression within cell clusters, together with the proportions of cells within each cluster and lineage, were assessed with respect to participant appendicular lean-mass index (ALMi), grip strength, and gait speed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Thirteen distinct cell clusters based on the transcriptional heterogeneity of the myoblasts were identified. Clusters 0–6 contained the majority (94.6%) of cells. Marker genes were enriched for cytoplasmic translation (Cluster 0, false discovery rate [FDR] = 7.21 × 10&lt;sup&gt;−63&lt;/sup&gt;), muscle development (Cluster 1, FDR = 2.25 × 10&lt;sup&gt;−13&lt;/sup&gt;), cell proliferation (Clusters 2, 4 and 6, all FDR ≤ 0.05), extracellular matrix organisation (Cluster 3, FDR = 1.92 × 10&lt;sup&gt;−45&lt;/sup&gt;) and RNA processing (Cluster 5, FDR = 1.89 × 10&lt;sup&gt;−08&lt;/sup&gt;). Individuals with the highest grip strength and ALMi had a greater proportion of Cluster 1 and Cluster 5 cells. Gene expression analysis (FDR ≤ 0.05) within the clusters identified 22 differentially expressed transcripts with respect to ALMi in Cluster 2 and 13 with respect to grip strength in Cluster 1. Inferred lineage analysis identified cells transitioning along five trajectories (L1–L5), including cells in L1, L3 and L4 progressing towards a stressed pre-senescent/senescent (L1) or fibrogenic (L3 and L4) state, with cells in these lineages being more likely to originate from individuals with low ALMi (χ&lt;sup&gt;2&lt;/sup&gt; &lt;i&gt;p&lt;/i&gt; = 1.11 × 10&lt;sup&gt;−146&lt;/sup&gt;) and grip strength (χ&lt;sup&gt;2&lt;/sup&gt; &lt;i&gt;p&lt;/i&gt; = 1.31 × 10&lt;sup&gt;−269&lt;/sup&gt;).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211601","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":"Combined Impact of Smoking Duration and Malnutrition on Cancer Survival: Insights Into Systemic Inflammation","authors":"Hong Zhao,&nbsp;Bing Yin,&nbsp;Zhe Zhao,&nbsp;Xiangrui Li,&nbsp;Changhong Xu,&nbsp;Yi Li,&nbsp;Zhaoting Bu,&nbsp;Xinyin Chen,&nbsp;Hanping Shi","doi":"10.1002/jcsm.70207","DOIUrl":"10.1002/jcsm.70207","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Smoking and malnutrition are established risk factors for cancer survival, yet evidence on their combined effects remains limited. This study aimed to investigate the joint impact of smoking duration and malnutrition on overall survival (OS) in patients with solid tumours and to explore the potential underlying mechanism—systemic inflammation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study was based on the Investigation of Nutrition Status and Clinical Outcomes in Common Cancers (INSCOC), which enrolled 29 988 patients with solid tumours and collected data on smoking status, nutritional status assessed by the Patient-Generated Subjective Global Assessment (PG-SGA) and haematological indicators. Restricted cubic spline regression, Cox proportional hazards models and logistic regression were used to examine the associations of smoking and malnutrition with OS and their relationships with inflammatory markers.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 29 988 patients were included, among whom 7649 were smokers with malnutrition (male: 7095 [92.8%]; female: 554 [7.2%]); their mean age was 60.17 ± 10.57 years. Both smoking and malnutrition independently increased mortality risk in patients with solid tumours (HR = 1.24, 95% CI 1.15–1.35, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; HR = 1.25, 95% CI 1.17–1.33, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), with the highest risk observed in those with both risk factors (HR = 1.46, 95% CI 1.36–1.57, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Smoking duration showed a dose–response association with OS. Specifically, among smokers, every additional 5 years of smoking increased the risk of death by 6% (HR = 1.06, 95% CI 1.04–1.07, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). In patients with malnutrition, every additional 10 years of smoking increased the risk of death by 86% (HR = 1.86, 95% CI 1.55–2.23, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Further analyses showed that, with increasing smoking duration, CRP increased from 3.50 [1.79, 13.60] to 6.00 [2.87, 24.90] mg/L and WBC from 5.70 [4.47, 7.31] to 6.47 [5.10, 8.40] × 10&lt;sup&gt;9&lt;/sup&gt;/L (both &lt;i&gt;p&lt;/i&gt; &lt; 0.001). With worsening malnutrition, CRP rose from 3.11 [1.23, 6.28] to 10.00 [3.20, 40.70] mg/L and WBC from 5.70 [4.51, 7.24] to 6.39 [4.84, 8.71] × 10&lt;sup&gt;9&lt;/sup&gt;/L (both &lt;i&gt;p&lt;/i&gt; &lt; 0.001), indicating that prolonged smoking and aggravated malnutrition were associated with elevated systemic inflammation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Smoking and malnutrition are crucial prognostic factors for survival in cancer patients. The results emphasize the critical role of managing ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146210240","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":"Disruption of Nuclear-Cytoskeletal Linkage by Coil-1a LMNA Mutations in Emery–Dreifuss Muscular Dystrophy","authors":"So-mi Kang,&nbsp;Ran Kim,&nbsp;Tae-Gyun Woo,&nbsp;Soyoung Park,&nbsp;Yeongseon Ji,&nbsp;Ha Eun Kim,&nbsp;Yu Jin Jeong,&nbsp;Jeongmo Kim,&nbsp;Yeonhee Kim,&nbsp;Woochul Chang,&nbsp;Bae-Hoon Kim,&nbsp;Bum-Joon Park","doi":"10.1002/jcsm.70234","DOIUrl":"10.1002/jcsm.70234","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Emery–Dreifuss muscular dystrophy (EDMD) is a progressive genetic myopathy that mainly affects the muscles used for movement (skeletal muscles) and the heart (cardiac muscles). The disease is frequently associated with mutations in genes encoding nuclear envelope proteins, most notably LMNA, which encodes lamin A—a critical structural component of the nuclear lamina. Lamin A plays a pivotal role in maintaining nuclear architecture and mechanotransduction. In contrast to most other cell types, nuclei in healthy skeletal muscle fibres are typically localized at the periphery of the myofiber. However, muscle biopsies from EDMD patients often reveal aberrant nuclear morphology and ectopic nuclear positioning, with nuclei clustered or mislocalized toward the centre of the myofiber. Despite these characteristic nuclear abnormalities, the molecular mechanisms underlying nuclear mispositioning in EDMD remain incompletely understood. In particular, the interaction networks between EDMD-related mutant lamin A and other nuclear and cytoskeletal components that govern nuclear positioning are poorly characterized in the current literature.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;EDMD-related lamin A variants (L35V, L38F or Y45C), which are located within the Coil-1a domain, were overexpressed in RD cells. Mesenchymal stem cells (MSCs) were generated by redifferentiating induced pluripotent stem cells (iPSCs), which were derived from fibroblasts of an EDMD (L35P) patient. To investigate morphological and molecular abnormalities caused by mutations, immunofluorescence imaging, immunoblotting and subcellular fractionation were performed. Functional consequences of these morphological alterations were evaluated by assessing mechanotransduction signalling and cell viability.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;EDMD-related LMNA mutations (L35V, L38F, Y45C) in the Coil-1a domain induced multilobular nuclear morphology, accompanied by a decrease in nuclear contour ratio (1.9–3.0-fold vs. WT, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Similarly, patient-derived MSCs (L35P-MSCs) exhibited a ~2.28-fold decrease in contour ratio relative to healthy subject-derived MSCs. Abnormal nuclear shape was associated with structural alterations in nuclear-cytoskeletal proteins and nuclear positioning regulators. Mechanosensing activity, assessed by YAP1 nuclear translocation, was increased (~1.72-fold vs. Nor-CTRL, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), and nuclear fragility under physical stress was elevated by ~20% (vs. Nor-CTRL, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Treatment with mutation-specific ASOs in patient-derived MSCs restored the contour ratio (~1.97-fold vs. NC-CTR","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215790","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":"Loss of Myonuclei and Transcriptional Activity During Diaphragm Atrophy in Critically Ill Patients","authors":"Wout J. Claassen,&nbsp;Marloes van den Berg,&nbsp;Zhong Hua Shi,&nbsp;Rianne. J. Baelde,&nbsp;Sylvia Bogaards,&nbsp;Luuk Bonis,&nbsp;Heleen Hakkeling,&nbsp;Arezou Bamyani,&nbsp;Gerben J. Schaaf,&nbsp;Albertus Beishuizen,&nbsp;Chris Dickhoff,&nbsp;Reinier A. Boon,&nbsp;Leo Heunks,&nbsp;Tyler J. Kirby,&nbsp;Coen A. C. Ottenheijm","doi":"10.1002/jcsm.70228","DOIUrl":"10.1002/jcsm.70228","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Diaphragm weakness frequently develops in critically ill patients and is explained by a combination of atrophy and myofiber dysfunction. Myofibers are large syncytial cells maintained by a population of myonuclei, which provide gene transcripts to a finite fiber volume, termed the myonuclear domain. Myonuclear number is a determinant of transcriptional capacity and therefore critical for diaphragm and peripheral muscle regeneration after critical illness. Changes in myonuclear number in myofibers undergoing atrophy have not been investigated in mechanically ventilated ICU patients, but they are of potential clinical importance. Our objective was to investigate if and how myonuclear number changes in the diaphragm of mechanically ventilated ICU patients and whether changes are associated with myofiber atrophy and clinical parameters.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We used a combination of transcriptomics, immunohistochemistry and confocal microscopy to study myonuclear alterations in the diaphragm and quadriceps biopsies from mechanically ventilated ICU patients (&lt;i&gt;n&lt;/i&gt; = 24) and non-critically ill patients (&lt;i&gt;n&lt;/i&gt; = 10).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Compared to control patients, myonuclear number and myonuclear domain were reduced in critically ill patients with diaphragm myofiber atrophy (&lt;i&gt;n&lt;/i&gt; = 14) (myonuclear number per mm of 133 [92–183] vs. 92 [83–105], &lt;i&gt;p&lt;/i&gt; = 0.03 (slow myofibers) and 149 [118–189] vs. 88 [69–109], &lt;i&gt;p&lt;/i&gt; = 0.004 (fast myofibers); myonuclear domain size was 44 [34–51] vs. 29 pL, &lt;i&gt;p&lt;/i&gt; = 0.004 (slow myofibers) and 41 [39–48] vs. 27 pL, &lt;i&gt;p&lt;/i&gt; = 0.001 (fast myofibers) of control patients and ICU patients with atrophy, respectively). Increased intrinsic apoptotic pathway activation was identified as a mechanism underlying myonuclear removal (percentage of apoptotic myonuclei of 0.64 [0.60–0.84] and 0.95 [0.84–1.2], &lt;i&gt;p&lt;/i&gt; = 0.015 and increased percentage of activated caspase-3 positive myonuclei of 2,5 [1.6–3.3] vs. 5.7 [4.3–11], &lt;i&gt;p&lt;/i&gt; = 0.001 in control patients and ICU patients with atrophy, respectively). Total transcriptional activity in myofibers decreased with myonuclear loss (RNA-Pol-2 Ser5 fluorescence intensity per fibre of 2.6 [2.2–3.3] vs. 5.8 [3.1–6.7] AU, &lt;i&gt;p&lt;/i&gt; = 0.036 in control patients and ICU patients with atrophy, respectively). Furthermore, muscle stem cell number was reduced in the patients with diaphragm atrophy (PAX7 positive nuclei per myofiber of 0.10 [0.09–0.11] vs. 0.05 [0.04–0.07], &lt;i&gt;p&lt;/i&gt; = 0.002 in control patients and ICU patients with atrophy, respectively). No correlation was found between myonuclea","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198776","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":"Single-Nucleus Transcriptome Reveals Cellular Heterogeneity and Transcriptional Response to Heat Stress in Skeletal Muscle","authors":"Ziyin Han,&nbsp;Li Chen,&nbsp;Zhiyu Lei,&nbsp;Jiaman Zhang,&nbsp;Ziyu Chen,&nbsp;Xiaolan Fan,&nbsp;Bo Zeng,&nbsp;Anan Jiang,&nbsp;Hai Xiang,&nbsp;Hua Li,&nbsp;Mingzhou Li,&nbsp;Long Jin","doi":"10.1002/jcsm.70217","DOIUrl":"10.1002/jcsm.70217","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Heat stress can induce skeletal muscle injury. Typical characteristics of heat-exposed muscle tissues include apoptosis, oxidative stress and autophagy. The understanding of molecular mechanisms underlying heat stress-induced muscle injury is limited, especially at the single-cell transcription level.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We collected skeletal muscles from 12-week-old female C57BL/6J mice in control (NC) and four heat stress groups. The experimental scheme comprised five groups: NC (25.5°C ± 0.5°C), HS0 (after ~3-h heat exposure, 41.5°C ± 0.5°C), HS8, HS16 and HS24 group (recovery at 25.5°C ± 0.5°C for 8, 16 and 24 h, respectively). Skeletal muscles were subjected to HE staining (&lt;i&gt;n&lt;/i&gt; = 6), TUNEL staining (&lt;i&gt;n&lt;/i&gt; = 3) and transmission electron microscopy (&lt;i&gt;n&lt;/i&gt; = 3). Transcripts were measured at the tissue (&lt;i&gt;n&lt;/i&gt; = 5 or 6) and single-nucleus levels (&lt;i&gt;n&lt;/i&gt; = 2).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Histologically, myofibrillar structure deformation, mitochondrial swelling and fusion, intramuscular triglyceride accumulation and autophagy occurred in the muscles subjected to heat stress. At the tissue level, a gene cluster associated with the response to heat exhibited an increasing trend of transcription in the HS0 versus NC groups, and the levels decreased to those in the NC group after 16 h. At the single-cell level, 134 320 high-quality myonuclei were collected from the muscles and annotated as seven cell types, including myonuclei, muscle stem cells (MuSCs) and immune cells. We identified the larger number of differentially expressed genes in the myonuclei. After heat stress, new cell clusters appeared in type IIa/IIx (HS8 group) and IIb (HS0 group) myonuclei but not in type I myonuclei. Generally, immediate early genes, highly expressed genes and transcription factor regulons identified in new cell clusters induced by heat were related to responses to heat, heat shock, oxidative stress and antioxidative stress. To repair the injured muscles, MuSCs highly expressed the development-related genes, such as &lt;i&gt;Atp2a1&lt;/i&gt;, &lt;i&gt;Ckm&lt;/i&gt;, &lt;i&gt;Myh1&lt;/i&gt;, &lt;i&gt;Aldoa&lt;/i&gt;, &lt;i&gt;Pde4d&lt;/i&gt; and &lt;i&gt;Pdlim5&lt;/i&gt;. Analysis of cell–cell communication showed that &lt;i&gt;Dag1&lt;/i&gt; and &lt;i&gt;Egf&lt;/i&gt; signals associated with myonuclei were the underlying pathways that participated in repair tissues.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We constructed the largest transcriptomic dataset, to date, for heat-exposed skeletal muscles. At tissue resolution, the response of muscles to heat stre","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160402","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}