Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"In Reply: Estimating Appendicular Skeletal Muscle Mass in Studies Based on the CHARLS Database","authors":"Ya-Xi Luo, Xiu-Qing Yao","doi":"10.1002/jcsm.70039","DOIUrl":"https://doi.org/10.1002/jcsm.70039","url":null,"abstract":"<p>We thank Liu et al. for their commentary on our recent study exploring the bidirectional transitions of sarcopenia in older Chinese adults using CHARLS data [<span>1</span>]. Their letter raises several important methodological questions about the validity of estimating appendicular skeletal muscle mass (ASM) in large-scale cohort studies [<span>2</span>]. We appreciate the opportunity to clarify our approach and discuss its alignment with international standards.</p><p>We fully acknowledge that dual-energy X-ray absorptiometry (DXA) is the reference standard for ASM measurement. However, in large, population-based surveys such as CHARLS, DXA is not feasible due to logistical limitations and concerns regarding economic feasibility. Recognizing this, both the Asian Working Group for Sarcopenia (AWGS 2019) and the revised European Working Group on Sarcopenia in Older People (EWGSOP2) explicitly endorse the use of validated anthropometric equations when direct imaging is unavailable [<span>3, 4</span>]. Our study employed the widely used equation by Wen et al., developed and validated in a Chinese adult population, which has shown strong correlation with DXA-measured ASM [<span>5</span>]. This equation has been widely adopted in longitudinal CHARLS studies examining outcomes ranging from mortality to cognitive decline.</p><p>A key concern raised was the age mismatch between the derivation cohort of the Wen equation and our elderly sample. While this is a valid point, the formula includes age, sex, height and weight, accounting for key covariates influencing muscle mass. More importantly, we applied an internal standardization strategy: defining low muscle mass based on the sex-specific 20th percentile of ASM/height<sup>2</sup> within the CHARLS population. This approach is well supported in epidemiological literature. In a population-based study, Coin et al. demonstrated that applying the 20th percentile of ASM/height<sup>2</sup> for an elderly reference population provided a more sensitive and appropriate method for identifying sarcopenia-related risk than using absolute cut-offs derived from younger populations [<span>6</span>]. The choice to use internal percentiles also addresses another concern: secular trends in anthropometric variables. Instead of applying fixed cut-offs from external cohorts or historical reference data, internal thresholds inherently reflect the specific characteristics of the study population at that time. This improves classification accuracy, especially in populations where height and body composition may shift across generations.</p><p>Liu et al. also pointed out that more comprehensive anthropometric equations, such as those incorporating calf circumference, may improve ASM prediction. We agree that these newer models represent an important methodological advance. Indeed, a recently proposed calf-inclusive anthropometric model for older Chinese adults demonstrated strong agreement with bioelectrical impedance analys","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705167","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 ‘Quantification of Skeletal Muscle at the First Lumbar Level for Prognosis in Amyotrophic Lateral Sclerosis’ by Cao et al.","authors":"Josef Finsterer","doi":"10.1002/jcsm.70038","DOIUrl":"https://doi.org/10.1002/jcsm.70038","url":null,"abstract":"<p>We were interested to read the article by Cao et al. on a cohort study on the validity of L1-level skeletal and paraspinal muscle density and area on chest CT (SMD, SMA, PMA and PMD) and subcutaneous area and density (SFA and SFD) to assess severity and outcomes in 102 patients with sporadic and familial amyotrophic lateral sclerosis (SALS and FALS) [<span>1</span>]. SMD, SMA, PMA and PMD were lower in ALS patients, and SFA and SFD were higher than in control subjects [<span>1</span>]. The ALS Functional Rating Scale-Revised (ALSFRS-R) increased with increasing SMA, skeletal muscle index (SMI) and PMA [<span>1</span>]. SMD, SMA and PMD significantly influenced ALS survival [<span>1</span>]. The study is remarkable, but some ambiguities should be clarified.</p><p>The first point is that ALS is currently diagnosed according to the Gold Coast criteria [<span>2</span>]. What is the reason that the revised Awaji-Shima criteria were used to diagnose definite, probable, and possible ALS? How many of the included patients did not have ALS when the Gold Coast criteria were applied?</p><p>The second point is that ALS can occur in the limbs as well as the trunk, suggesting that skeletal and paraspinal muscle mass may be lower in patients with bulbar onset than in those with limb ALS. We should know how many of the included patients had limb-onset ALS and how many had bulbar ALS and whether there was a difference in outcome parameters between these two groups.</p><p>The third point is that the chest CT was performed only once and was not repeated after a certain time. To assess whether muscle parameters actually worsened with disease progression and how this affected survival and outcome, it would have been useful to repeat the imaging studies.</p><p>The fourth point is that the outcome parameters can also depend heavily on the condition of the lumbar spine [<span>3</span>]. Therefore, we should know how many patients had scoliosis, lumbar malalignment, chondrosis, osteochondrosis, spondylosis, spondylarthrosis and osteoarthritis of the uncovertebral joints, spinal canal stenosis or myelopathy, and how this affects the outcome parameters.</p><p>The fifth point is that muscle mass may also depend on diet and nutritional status. Since ALS is often associated with dysphagia, it is conceivable that hypoproteinemia contributes to muscle loss and is more pronounced in patients with dysphagia than in patients without dysphagia. Was there a difference in outcome parameters between these two groups? In how many patients was a percutaneous gastrostomy (PEG) implanted?</p><p>The sixth point is that muscle mass may also depend on respiratory function, especially whether a patient is hypoxic or not. Therefore, we should know how many patients require oxygen supplementation, non-invasive ventilation, continuous positive airway pressure (CPAP) or a tracheostomy. A disadvantage in this respect is that only 40 patients had a pulmonary function test [<span>1</span>].</p><p","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705165","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":"Sarcopenia Is Associated With Increased Risk of Abnormal Sleep Duration in the Older People: A 10-Year Cohort Study From China","authors":"Yimi Wang,&nbsp;Weixin Chen,&nbsp;Chun Wang,&nbsp;Lingzhi Li,&nbsp;Bingqing Bi,&nbsp;Shugang Li,&nbsp;Hao Wu","doi":"10.1002/jcsm.70017","DOIUrl":"https://doi.org/10.1002/jcsm.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With the acceleration of the aging process, health issues of older people have gradually become one of the most important research topics. The older people experience significant reductions in muscle mass and physical performance. Cross-sectional studies have found an association between the sarcopenia and sleep duration. Due to lack of evidence of longitude study, it is necessary to investigate the association between sarcopenia and sleep duration in the older people.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study utilized longitudinal data including 2061 older people from China Health and Retirement Longitudinal Study 2011–2020. Diagnosis was made based on the Asian Working Group for Sarcopenia criteria 2019. There were 246 participants with sarcopenia, 628 participants with possible sarcopenia and 1187 participants with nonsarcopenia. Kaplan–Meier curve, log-rank test and Cox proportional risk model were used to explore the relationship between sarcopenia exposure and clinical outcome of abnormal sleep duration. Three models adjusting for different factors were built, and hazard ratios (HRs) were calculated. Restricted cubic spline analyses explored the exposure–response relationship between sarcopenia components and abnormal sleep duration incidence, while receiver operating characteristic curve was used to assess their predictive power.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The incidences of short or long, decreased sleep duration of the sarcopenia and possible sarcopenia groups in the overall population were significantly higher than those of the nonsarcopenia group (respectively, <i>p</i> &lt; 0.001). Sarcopenia (HR = 1.240, 95% CI [confidence interval]: 1.023–1.417) was significantly associated with an increased risk of abnormal sleep duration by Cox model analysis with adjusting factors. Results of analyses stratified by sleep duration showed that sarcopenia (HR = 1.566, 95% CI: 1.192–2.057) and possible sarcopenia (HR = 1.286, 95% CI: 1.054–1.570) were positively associated with long sleep duration. Higher ASM (<i>χ</i>^<i>2</i> = 94.02, <i>p</i> &lt; 0.001) and handgrip strength (<i>χ</i>^<i>2</i> = 94.55, <i>p</i> &lt; 0.001), as well as lower five-time chair stand test (<i>χ</i>^<i>2</i> = 81.33, <i>p</i> &lt; 0.001) showed an exposure-response relationship with sleep duration. The proportion of the condition of change in sleep duration from normal to &lt; 6 h or &gt; 8 h in the sarcopenia and possible sarcopenia groups was significantly different from the nonsarcopenia group (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705294","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 “Systematic Review and Meta-Analysis of Protein Intake to Support Muscle Mass and Function in Healthy Adults” by Nunes et al.","authors":"Omar Inca-Barriga,&nbsp;Piero Alberti-Nuñez,&nbsp;Miguel López-Moreno","doi":"10.1002/jcsm.70036","DOIUrl":"https://doi.org/10.1002/jcsm.70036","url":null,"abstract":"<p>We respectfully address you regarding the recently published article by Nunes et al., entitled ‘Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults’ [<span>1</span>]. The topic is highly relevant, and the study contributes valuable evidence to the field. However, we believe that certain methodological considerations may affect the interpretation and robustness of the conclusions drawn.</p><p>In the statistical analysis section, the authors state: ‘The analysis was conducted using change from baseline to immediate post-treatment data (means, standard deviations) for both intervention and control/placebo groups to generate summary measures of effect in the form of standardized mean differences (SMDs)’. This implies that the SMDs were calculated based on within-group pre-post changes rather than on the between-group differences at follow-up. However, this approach has been explicitly discouraged by the Cochrane Handbook of Systematic Reviews of Interventions (v6.4, Section 10.5.2), which cautions:</p><p>A particularly critical issue in the present meta-analysis concerns the apparent inclusion of multiple intervention arms from the same study as independent entries in the subgroup analysis, with SMDs calculated from pre-post differences within each arm. While this approach may allow for subgroup-specific exploration (e.g., stratified by protein intake), it introduces a unit-of-analysis error if multiple arms from the same study are analysed independently without accounting for shared sources of variance. According to Cochrane Handbook guidelines (v6.4, Section 23.3.4), this practice violates the assumption of independence across comparisons and can artificially narrow confidence intervals, thereby inflating the precision of the summary effect size [<span>2</span>]. Given that no advanced statistical techniques (e.g., multivariate meta-analysis) were employed to account for this dependence, the reported results likely overstate both the certainty and magnitude of the observed effects.</p><p>The analysis of the forest plot in Figure 2, which includes studies with protein intakes ≥ 1.6 g/kg/day, reveals that only four out of the 20 studies reported statistically significant effects. However, it is important to note that one of these studies—Burke et al.—found significant within-group changes but did not report statistically significant between-group differences [<span>4</span>]. Including this study in the analysis as if it had demonstrated superiority of the intervention group over placebo could have artificially contributed to the statistical significance of the subgroup, potentially leading to an overinterpretation of the intervention's efficacy at this protein intake threshold.</p><p>A relevant point to consider is that the study by Willoughby et al. presents outlier results favouring the intervention with dietary protein. In this study, the protein-supplemented group also exhibited an incre","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705166","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":"ODIASP: An Open-Source Software for Automated SMI Determination—Application to an Inpatient Population","authors":"Katia Charrière,&nbsp;Antoine Ragusa,&nbsp;Béatrice Genoux,&nbsp;Antoine Vilotitch,&nbsp;Svetlana Artemova,&nbsp;Charlène Dumont,&nbsp;Paul-Antoine Beaudoin,&nbsp;Pierre-Ephrem Madiot,&nbsp;Gilbert R. Ferretti,&nbsp;Ivan Bricault,&nbsp;Eric Fontaine,&nbsp;Jean-Luc Bosson,&nbsp;Alexandre Moreau-Gaudry,&nbsp;Joris Giai,&nbsp;Cécile Bétry","doi":"10.1002/jcsm.70023","DOIUrl":"https://doi.org/10.1002/jcsm.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The diagnosis of malnutrition has evolved with the GLIM recommendations, which advocate for integrating phenotypic criteria, including muscle mass measurement. The GLIM framework specifically suggests using skeletal muscle index (SMI) assessed via CT scan at the third lumbar level (L3) as a first-line approach. However, manual segmentation of muscle from CT images is often time-consuming and infrequently performed in clinical practice. This study is aimed at developing and validating an open-access, simple software tool called ODIASP for automated SMI determination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were retrospectively collected from a clinical data warehouse at Grenoble Alpes University Hospital, including epidemiological and imaging data from CT scans. All consecutive adult patients admitted in 2018 to our tertiary centre who underwent at least one CT scan capturing images at the L3 vertebral level and had a recorded height were included. ODIASP combines two algorithms to automate L3 slice selection and skeletal muscle segmentation, ensuring a seamless process. Agreement between cross-sectional muscle area (CSMA) values obtained using ODIASP and the reference methodology (i.e., manual determination) was evaluated using the intraclass correlation coefficient (ICC). The prevalence of reduced SMI was also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SMI was available for 2503 participants, 53.3% male, with a median age of 66 years (51–78) and a median BMI of 24.8 kg/m² (21.7–28.7). In a validation subset of 674 scans, agreement between the reference method and ODIASP was substantial (ICC: 0.971; 95% CI: 0.825–0.989) and improved to excellent (ICC: 0.984; 95% CI: 0.982–0.986) after correcting for systematic overestimation (a 5.8 cm² [5.4–6.3]) indicating excellent agreement. The prevalence of reduced SMI was 9.1% overall (11.0% in men and 6.6% in women). The ODIASP software is available as a downloadable executable to support its use in research settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that ODIASP is a reliable tool for automated SMI at the L3 vertebra level from CT scans. The integration of validated AI algorithms into a simple, open-source software enables scalable, standardised assessment of SMI in diverse patient populations and supports future integration into clinical workflows for improved nutritional assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705698","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 ‘A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses’ by Ren et al.","authors":"Guanghao Zheng,&nbsp;Yu Cheng,&nbsp;Tao Zeng","doi":"10.1002/jcsm.70035","DOIUrl":"https://doi.org/10.1002/jcsm.70035","url":null,"abstract":"&lt;p&gt;We read with great interest the article titled ‘A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses’ in your esteemed journal [&lt;span&gt;1&lt;/span&gt;]. By innovatively integrating cross-sectional observational analysis with Mendelian Randomization (MR) approaches, this study provides important insights into the potential causal role of 25(OH)D status in appendicular muscle mass (AMM) maintenance, offering valuable implications for developing targeted interventions against sarcopenia, particularly in male populations. The authors established a rigorous analytical framework through two complementary phases: First, multivariable-adjusted regression models based on NHANES data consistently demonstrated a dose-dependent association between serum 25(OH)D concentrations and AMM. Building on these observational findings, the investigators performed two-sample MR analyses using genome-wide significant single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels. The MR results revealed a positive causal relationship between genetically predicted 25(OH)D levels and AMM. This methodological progression from observational epidemiology to causal inference not only mitigates residual confounding inherent in observational designs but also provides compelling genetic evidence supporting 25(OH)D supplementation as a potential sex-specific preventive strategy against sarcopenia, particularly advancing our understanding of musculoskeletal health in males. However, to enhance the rigour and reliability of the findings, we would like to offer several constructive suggestions regarding key aspects of the study design.&lt;/p&gt;&lt;p&gt;In MR analyses, instrumental variables (IVs) must satisfy three core assumptions: relevance, independence and exclusion restriction assumption [&lt;span&gt;2&lt;/span&gt;]. While the authors have thoroughly discussed these assumptions and implemented stringent quality control measures, further scrutiny using the LDtrait database revealed that several selected SNPs (e.g., rs1047891, rs11076175, rs11204743, rs1260326, rs2756119, rs4616820, rs512083, rs55707527, rs55872725, rs6011153, rs72862854, rs7528419, rs7864910, rs804281 and rs8107974) are significantly associated with the outcome variable, AMM [&lt;span&gt;3&lt;/span&gt;]. This suggests the potential presence of horizontal pleiotropy, which may violate the exclusion restriction assumption and compromise the accuracy of causal inference. To improve robustness, we recommend conducting additional forward and reverse MR analyses, excluding SNPs with possible pleiotropic effects.&lt;/p&gt;&lt;p&gt;Secondly, a key prerequisite of two-sample MR is that the exposure and outcome data are derived from two independent, nonoverlapping populations with similar demographic characteristics [&lt;span&gt;2&lt;/span&gt;]. Unfortunately, it appears that this has not been done by Ren et al. In this study, both the GWAS data for serum 25(OH)D levels and AMM were sourced from the U","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695824","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":"Association of Difference Between eGFR From Cystatin C and Creatinine and Serum GDF-15 With Adverse Outcomes in Diabetes Mellitus","authors":"Tomohito Gohda,&nbsp;Nozomu Kamei,&nbsp;Marenao Tanaka,&nbsp;Masato Furuhashi,&nbsp;Tatsuya Sato,&nbsp;Mitsunobu Kubota,&nbsp;Michiyoshi Sanuki,&nbsp;Takeo Koshida,&nbsp;Shinji Hagiwara,&nbsp;Yusuke Suzuki,&nbsp;Maki Murakoshi","doi":"10.1002/jcsm.70011","DOIUrl":"https://doi.org/10.1002/jcsm.70011","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;Protein catabolism and chronic inflammation drive sarcopenia and frailty in individuals with diabetes mellitus and chronic kidney disease (CKD). The difference between estimated glomerular filtration rates derived from cystatin C and creatinine (eGFRcys and eGFRcr, respectively), termed eGFRdiff, along with growth differentiation factor-15 (GDF-15) levels, have emerged as markers of metabolic and inflammatory dysregulation. Lower eGFRdiff and elevated GDF-15 levels are associated with sarcopenia, frailty, CKD progression and mortality. However, their interplay and respective impacts on CKD progression and mortality remain unclear.&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;A total of 638 Japanese individuals with diabetes mellitus were stratified into tertiles based on eGFRdiff. Serum GDF-15 levels were measured using enzyme-linked immunosorbent assays. The relationships between eGFRdiff and GDF-15 were assessed using Spearman's correlation coefficients. Multivariate ordered logistic regression was used to evaluate the association between eGFRdiff and GDF-15 tertiles, with GDF-15 as the dependent variable and eGFRdiff as the independent variable, adjusting for covariates including age, sex, urinary albumin-to-creatinine ratio (UACR) and eGFRcr or eGFRcys. Cox proportional hazards models with restricted cubic splines were used to examine associations between eGFRdiff and GDF-15 (independent variables) with CKD progression (≥ 30% decline in eGFRcr from baseline) and mortality (dependent variables). These models were adjusted for age, sex, glycated haemoglobin, UACR and eGFRcr.&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;The median age was 65 years (interquartile range: 58–73), and 53.9% of participants were male. Over median follow-up periods of 5.3 years for CKD progression and 5.4 years for mortality, 75 participants (11.8%) experienced CKD progression and 44 (6.9%) died. GDF-15 levels inversely correlated with eGFRdiff (&lt;i&gt;r&lt;/i&gt; = −0.35, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Higher eGFRdiff values were associated with lower odds of being in a higher GDF-15 tertile (odds ratio 0.86; 95% confidence interval [CI]: 0.76–0.97; &lt;i&gt;p&lt;/i&gt; = 0.01). Both lower eGFRdiff and higher GDF-15 levels were independently associated with adverse outcomes: CKD progression (GDF-15, hazard ratio [HR] 1.36, 95% CI: 1.02–1.81, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; eGFRdiff, HR 0.67, 95% CI: 0.58–0.78, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and mortality (GDF-15, HR 2.35, 95% CI: 1.63–3.41, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; eGFRdiff: 0.80, 95% CI: 0.65–0.99, &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688000","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":"Thymic Microenvironment Remodeling in Cancer Cachexia as a Determinant of Checkpoint Inhibitor Efficacy and Toxicity","authors":"Run-Kai Huang,&nbsp;Yan-Fang Xing,&nbsp;Xiang-Yuan Wu,&nbsp;Zhao-Hui Shi,&nbsp;Li Wei,&nbsp;Xiao-Tong Lv,&nbsp;Lin-Jiao Peng,&nbsp;Xiu-Qing Pang,&nbsp;Qin-Tai Yang,&nbsp;Xing Li","doi":"10.1002/jcsm.13874","DOIUrl":"https://doi.org/10.1002/jcsm.13874","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The discovery of immune checkpoints links autoimmunity and cancer, with thymus atrophy reportedly causing autoimmune multiorgan inflammation. The impact of cancer cachexia on thymic involution and its clinical significance remains unclear. This study aimed to investigate this effect and its association with immune checkpoint inhibitor (ICI) treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell sequencing, immunofluorescence and flow cytometry analyses were conducted to explore changes in the thymus in orthotopic hepatocellular cancer (HCC) mice with cachexia. Patients with advanced and locally advanced cancers receiving anti-PD-1/L1 antibody treatment were followed up to investigate the relationship between the amount of serum autoantibodies and the efficacy of ICIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Single-cell sequencing in cachexic HCC mice revealed thymic fibroblast maturity disorders characterized by elevated immature medullary fibroblasts, impaired antigen processing functions, reduced interaction with single-positive thymocytes and decreased expression of tissue-restricted antigen-related genes. The thymus of mice with cancer cachexia exhibited degradation of the thymic medulla and decreased expression of LtβR, Mmp9 and Ccl19 in thymus medullary fibroblasts (mFbs). Single-cell TCR sequencing showed that inflammatory-related V/J TCR genes were highly used in expanded thymocyte clonotypes in cachexic HCC mice, suggesting impaired T cell negative selection. Results from coculture and cell transfer assays suggest that cancer cachexic CD45⁺ erythroid progenitor cells (EPCs) induce the death of CD34⁺ progenitor cells and decrease the number of LtβR⁺, Mmp9⁺ and Ccl19⁺ mFbs in tumour-free mice. CD24⁺CD4⁺CD8⁻ single-positive thymocytes, typically eliminated in negative selection, did not decrease after the administration of anti-CD3 mAb. Serum autoantibodies were markedly produced in cachexic HCC mice, cachexic HCC mice administered with anti-PD1 and tumour-free mice that received cancer cachexic CD45⁺ EPCs. Autoantibodies against tumour-restricted antigens were found in patients with advanced and locally advanced cancer who received two cycles of ICI treatment. Univariate Cox regression analysis showed that patients with a low level of autoantibodies had a higher risk of disease progression (hazard ratio [HR]: 2.39, 95% CI [1.02–5.63], <i>p</i> = 0.046). Analysis of the receiver operating characteristic curve indicated that the number of autoantibodies against tumour tissues predicted t","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634980","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":"The Combination of Fat Distribution and BMI Redefines Obesity: Result From NHANES","authors":"Liuqing Yang,&nbsp;Yizhong Ge,&nbsp;Qiankun Zhu,&nbsp;Qi Zhang,&nbsp;Lin Wang,&nbsp;Xin Wang,&nbsp;Yun Yang,&nbsp;Hanping Shi","doi":"10.1002/jcsm.70013","DOIUrl":"https://doi.org/10.1002/jcsm.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Body mass index (BMI) has well-recognized limitations, particularly in the context of the ‘obesity paradox’, where higher BMI does not consistently evaluate adverse outcomes. These limitations underscore the need for alternative approaches. This study aimed to redefine obesity using anthropometric indicators and to assess their prognostic value for mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006. Additional dual-energy X-ray absorptiometry (DXA) data on fat distribution were sourced from NHANES 1999–2006 and 2011–2018. Ten fat distribution indicators were adopted to assess the fat distribution in the target population, including five centripetal obesity indicators, three global obesity indicators and two limb obesity indicators. All-cause, cardiovascular-specific and cancer-specific mortality outcomes were examined using weighted Cox proportional hazards models. Logistic regression was employed to evaluate associations between fat distribution indicators and the prevalence of specific diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study included 14 936 participants (weighted 152 823 236 participants, mean age: 45.56 ± 17.60 years) and two DXA-assessed cohorts. Fat distribution indicators were correlated with various DXA-defined fat components. All 10 indicators demonstrated significant associations with mortality. Notably, the relationship between centripetal obesity indicators and all-cause mortality was approximately linear in both sexes. Centripetal obesity was also strongly associated with cardiovascular and cancer-specific mortality (<i>p</i> &lt; 0.001). Although fat distribution indicators were significantly linked to the prevalence of cardiovascular disease (CVD), they showed no clear association with cancer incidence. Individuals with obesity but without centripetal fat accumulation exhibited a similar or slightly higher mortality risk compared with those with normal BMI and no centripetal obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Centripetal obesity indicators emerged as the strongest independent evaluators of mortality, regardless of BMI classification. These findings highlight the clinical value of incorporating fat distribution metrics alongside BMI to more accurately assess obesity-related mortality risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624518","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":"TAVI Success Is More Than Just the Valve: CT-Derived Sarcopenia as a Major Determinant of Long-Term Survival","authors":"Nikolaos Schörghofer,&nbsp;Christoph Knapitsch,&nbsp;Gretha Hecke,&nbsp;Nikolaus Clodi,&nbsp;Lucas Brandstetter,&nbsp;Crispiana Cozowicz,&nbsp;Matthias Hammerer,&nbsp;Klaus Hergan,&nbsp;Uta C. Hoppe,&nbsp;Bernhard Scharinger,&nbsp;Elke Boxhammer","doi":"10.1002/jcsm.70012","DOIUrl":"https://doi.org/10.1002/jcsm.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia, characterized by progressive skeletal muscle loss, is a silent yet powerful marker associated with survival, yet its impact on long-term outcomes in transcatheter aortic valve implantation (TAVI) remains underestimated. While frailty has been recognized as a main factor of resilience and recovery, the role of muscle integrity is frequently overlooked. This study explores whether computed tomography (CT)-derived psoas muscle area (PMA) and psoas muscle area index (PMI) are key predictors of post-TAVI survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 539 patients (mean age 82.0 ± 5.1 years; 49.9% female) undergoing TAVI were analysed in this retrospective, single-centre study. Sarcopenia was analysed via sex-specific quartiles of PMA and PMI. Long-term survival was examined using Kaplan–Meier analysis, univariate and multivariate Cox regression analysis. Interaction terms were introduced to assess whether the association between sarcopenia and survival differed by age, sex, renal function and anaemia status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sarcopenia emerged as a predictor of long-term mortality (HR = 1.52, <i>p</i> = 0.011 for PMA; HR = 1.55, <i>p</i> = 0.008 for PMI) after TAVI. Notably, younger patients (&lt; 80 years) with sarcopenia faced double the mortality risk (HR = 2.48, <i>p</i> = 0.001 for PMA; HR = 2.55, <i>p</i> = 0.001 for PMI), whereas in older patients, the association was weaker. In women, who typically show a post-TAVI survival advantage, sarcopenia reduced this benefit (HR = 1.75, <i>p</i> = 0.020 for PMA; HR = 1.88, <i>p</i> = 0.008 for PMI). The most striking finding was the synergistic effect of sarcopenia and chronic kidney disease (CKD), resulting in a threefold increase in mortality risk (HR = 2.82, <i>p</i> = 0.027 for PMA; HR 3.14, <i>p</i> = 0.011). After multivariate adjustment, sarcopenia remained a strong, independent predictor of long-term mortality (HR = 1.58, <i>p</i> = 0.009 for PMA; HR = 1.49, <i>p</i> = 0.024 for PMI), reinforcing its clinical relevance in TAVI risk stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggests that sarcopenia is not just a passive bystander, but may serve as a marker associated with long-term mortality in TAVI patients, especially in younger individuals, women and those with CKD or anaemia. Since muscle mass predicts survival and is potentially modifiable, assessing and intervening against sarcopenia before and after TAVI could represent a clinical priority in patients with ao","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598446","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}