Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Muscle Abnormalities in Nonhospitalised Patients With Post–COVID-19 Condition","authors":"Andrea Tryfonos, Gustav Jörnåker, Håkan Rundqvist, Kaveh Pourhamidi, Michael Melin, Helena Wallin, Filip J. Larsen, Spyridon Pantelios, Anders P. Mutvei, Veronika Tillander, Uwe J. F. Tietge, Sergio Perez Diaz, Douglas Crafoord, Alen Lovric, Rodrigo Fernandez-Gonzalo, Eric Rullman, Per Stål, Thomas Gustafsson, Helene Rundqvist, Tommy R. Lundberg","doi":"10.1002/jcsm.70085","DOIUrl":"10.1002/jcsm.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Post-COVID condition (PCC) affects ~10% of SARS-CoV-2–infected individuals and manifests as persistent symptoms such as fatigue, exercise intolerance and muscle weakness. This study aimed to assess the skeletal muscle of these patients and compare them with healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Biopsies were obtained from the vastus lateralis muscle of 28 nonhospitalised PCC patients without concomitant diseases (75% women, mean age 46.4 ± 10.4 years) and 28 age- and sex-matched healthy controls (79% women, mean age 46.6 ± 8.7 years). The analysis included morphological and pathological alterations, fibre type composition, fibre cross-sectional area, capillarisation, number of myonuclei, presence of developmental myosin, CD68<sup>+</sup> cells, macroautophagy markers, mitochondrial respiration, lipidomics and RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PCC patients, compared to controls, had a higher percentage of angulated fibres (median [IQR] 0.43 [0.00–3.20] vs. 0.00 [0.00–0.00]; <i>p</i> < 0.001), small, rounded fibres (0.21 [0.00–1.20] vs. 0.00 [0.00–0.00]; <i>p</i> < 0.001) and fibres expressing fetal myosin (0.26 [0.00–1.15] vs. 0.00 [0.00–0.17]; <i>p</i> = 0.015). Semiquantitative analysis showed nuclear clumps (18/27, 66.6%), hypertrophic fibres (9/27, 33.3%) and fibrosis (22/27, 81.4%) in PCC patients. Fibre cross-sectional area was significantly lower in PCC patients (4031 ± 1365 vs. 4982 ± 1463 μm<sup>2</sup>; <i>p</i> = 0.018), largely driven by differences in type 2 fibre size (3533 ± 1249 vs. 4275 ± 1646 μm<sup>2</sup>; <i>p</i> = 0.068) than type 1 fibre size (4553 ± 1422 vs. 4932 ± 1380 μm<sup>2</sup>; <i>p</i> = 0.325). There was a significantly lower number of myonuclei per fibre in PCC (3.4 ± 1.1 vs. 4.1 ± 1.0; <i>p</i> = 0.012), but no difference in the presence of CD68<sup>+</sup> per fibre (0.28 ± 0.15 vs. 0.22 ± 1.0; <i>p</i> = 0.115). No group differences were observed in macroautophagy markers LC3B (0.0032 ± 0.0007 vs. 0.0030 ± 0.0006; <i>p</i> = 0.232) or p62 (0.0072 ± 0.0023 vs. 0.0079 ± 0.0016; <i>p</i> = 0.814). Capillary-to-fibre ratio in PCC patients was lower for both type 1 (2.2 ± 0.7 vs. 2.6 ± 0.9; <i>p</i> = 0.044) and type 2 fibres (1.8 ± 0.6, vs. 2.2 ± 0.8; <i>p</i> = 0.022). Mitochondrial respiration was 11–28% lower in PCC patients, although not statistically significant. Lipidomics showed a lower number of phospholipids, and RNA sequencing revealed downregulation of eight metabolic pathways, primarily related to oxidative phosphorylation in PCC patients compared to controls (FDR < 0.05).</p>\u0000 </section>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194643","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":"Reduced Muscle Force in Dystrophic DMDΔ52 Pigs Is Incompletely Restored by Systemic Transcript Reframing (DMDΔ51–52)","authors":"Michaela Blasi, Hristiyan Hristov, Jan B. Stöckl, Martin Kraetzl, Sonja Fiedler, Elisabeth Kemter, Mayuko Kurome, Barbara Kessler, Josep M. Cambra, Valeri Zakhartchenko, Maggie C. Walter, Christian Kupatt, Nikolai Klymiuk, Thomas Fröhlich, Andreas Blutke, Michael Stirm, Florian Jaudas, Eckhard Wolf","doi":"10.1002/jcsm.70084","DOIUrl":"10.1002/jcsm.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Duchenne muscular dystrophy (DMD) is a fatal X-linked disease caused by mutations in the <i>DMD</i> gene, leading to dystrophin deficiency and progressive degeneration of skeletal and cardiac muscles. Pigs lacking <i>DMD</i> exon 52 (<i>DMD</i>Δ52) are a clinically severe model for DMD, mimicking molecular, functional and pathological hallmarks of the human disease. Dystrophin expression can be restored by additionally deleting exon 51 (<i>DMD</i>Δ51–52), which reframes <i>DMD</i> transcripts and alleviates pathological alterations. <i>DMD</i>Δ51–52 pigs model Becker muscular dystrophy (BMD), a milder and slower-progressing form of muscle degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Aurora Swine Isometric Footplate Test Apparatus was used to quantify functional parameters of the hind limb dorsiflexor muscle group of 3.5-month-old DMD pigs (<i>n</i> = 5), BMD pigs (<i>n</i> = 3) and wild-type (WT) littermate controls (<i>n</i> = 3). In addition, histopathological and proteomic studies of the functionally tested muscles were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After twitch stimulation, DMD muscle achieved 62.4% (<i>p</i> < 0.05) and BMD muscle 67.1% (<i>p</i> < 0.05) of the absolute peak force of WT muscle, indicating partial but not complete restoration of muscle force by <i>DMD</i>Δ51–52 transcript reframing. After normalization to the cube root of body mass, the values were 70.9% for DMD muscle (<i>p</i> = 0.05) and 65.8% for BMD muscle (<i>p</i> < 0.05). DMD muscle showed a reduced rate of contraction (<i>p</i> < 0.01); the rate of relaxation was decreased in both DMD (<i>p</i> < 0.01) and BMD (<i>p</i> < 0.05) compared with WT muscle. After tetanic stimulation, DMD muscle reached 54.7% (<i>p</i> < 0.001) and BMD muscle 80.4% (<i>p</i> = 0.08) of WT muscle force. Normalized values were 62.7% (DMD; <i>p</i> < 0.01) and 79.3% (BMD; <i>p</i> = 0.08). The rate of contraction was reduced in both DMD (<i>p</i> < 0.001) and BMD muscle (<i>p</i> < 0.01), whereas the return to the resting state was prolonged (<i>p</i> < 0.001) only in DMD vs. WT muscle. Histopathology and proteomics revealed no significant differences between BMD and WT muscles, whereas severe alterations were observed in DMD pigs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study pioneers the quantitative assessment of skeletal muscle function in dystrophic pigs. It demonstrates that systemic exon 51 skipping in DMD caused by loss of <i>DMD</i> exon 52 partially rest","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197613","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":"Impact of Muscle Mass on the Performance of Creatinine-Based eGFR Equations and Mortality Risk Assessment After Kidney Transplantation","authors":"François Gaillard,&nbsp;Melissa Ould Rabah,&nbsp;Olivier Aubert,&nbsp;Nicolas Garcelon,&nbsp;Antoine Neuraz,&nbsp;Christophe Legendre,&nbsp;Dany Anglicheau,&nbsp;Dominique Prié,&nbsp;Frank Bienaimé","doi":"10.1002/jcsm.70032","DOIUrl":"10.1002/jcsm.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Estimating glomerular filtration rate (eGFR) in kidney transplant recipients (KTR) typically relies on plasma creatinine, which is influenced by muscle mass. Reduced muscle mass is suspected to reduce eGFR performance in this population but this effect has not been rigorously evaluated. This study quantified the impact of muscle mass on eGFR accuracy and its confounding effect on the association between kidney function and mortality in KTR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied a prospective and consecutive cohort of 1829 KTR (mean age 52 ± 14 years; 38.9% female) who underwent GFR measurement using iohexol clearance (ioGFR). Muscle mass was assessed by creatinine excretion rate (CER) from timed urine collections. We evaluated the impact of muscle mass on the performance of five eGFR equations (MDRD, CKDEPI₂₀₀₉, CKDEPI₂₀₂₁, EKFC and RFKTS) using multiple regression and subgroup analysis. The association between eGFRs, ioGFR and mortality was examined using Cox proportional hazards models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All eGFR equations showed a significant negative correlation with CER. EKFC was the least sensitive to CER (<b><i>β</i></b> coefficient 95% confidence interval [CI]: −0.17 to −0.12). All eGFR equations demonstrated reduced accuracy in the lowest muscle mass tertile. In multivariable analyses, ioGFR was significantly associated with mortality (hazard ratio 95% CI: 0.972–0.995) but eGFRs were not. Including CER in the Cox models resulted in convergence of the mortality hazard ratios for ioGFR and eGFRs (hazard ratio 95% CI: ioGFR: 0.98–0.999; MDRD: 0.98–0.999; CKDEPI₂₀₂₁: 0.99–1; EKFC (0.98–1) RFKS: 0.98–0999).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The performance of all tested creatinine-based eGFR equations is strongly impacted by muscle mass. Muscle mass is also a key confounder in the mortality risk assessment using eGFR. Incorporating muscle mass into KTR's evaluations may improve kidney function assessments in KTR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183106","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 \"Risk of Sarcopenia Following Long-Term Statin Use in Community-Dwelling Middle-Aged and Older Adults in Japan\" by Huang et al. - The Authors Reply","authors":"Shih-Tsung Huang,&nbsp;Fei-Yuan Hsiao,&nbsp;Liang-Kung Chen,&nbsp;Hidenori Arai","doi":"10.1002/jcsm.70070","DOIUrl":"10.1002/jcsm.70070","url":null,"abstract":"&lt;p&gt;We appreciate Dr. Huang's interest in our study ‘Risk of Sarcopenia Following Long-Term Statin Use in Community-Dwelling Middle-Aged and Older Adults in Japan’ and his thoughtful comments regarding our methodology [&lt;span&gt;1&lt;/span&gt;]. We would like to address the concerns raised in his letter.&lt;/p&gt;&lt;p&gt;First, regarding the standardized mean difference (SMD) of exactly 0.00 for age after propensity score matching, we understand this observation might raise questions about potential data or calculation errors. We want to clarify that this perfect balance for age was not coincidental or erroneous, but rather the result of our methodological approach. In geriatric epidemiology research, age is a critical confounding factor that significantly influences outcomes related to muscle health and sarcopenia [&lt;span&gt;2&lt;/span&gt;]. Therefore, in addition to our standard propensity score matching criteria, we specifically required exact age matching during the matching process. This additional constraint explains why age demonstrates a perfect SMD of 0.00, while other variables in Table 1 show varying degrees of balance after matching [&lt;span&gt;3&lt;/span&gt;]. The absence of perfect SMDs for other variables confirms that our data processing was sound and that the matching procedure functioned as intended.&lt;/p&gt;&lt;p&gt;Second, regarding the exact matching procedures used when sampling with replacement in our risk set sampling methodology, we implemented a systematic approach that maintained methodological rigour while addressing the challenges inherent in longitudinal studies with time-varying exposures. For each wave of our study, we identified all subjects who initiated statin therapy (exposed) and all concurrent nonusers (unexposed). For every exposed subject, we established a risk set comprising all unexposed individuals at that specific time point. We then calculated propensity scores using multivariable logistic regression models that incorporated all relevant baseline covariates, including demographic characteristics, health status indicators, and comorbidities.&lt;/p&gt;&lt;p&gt;The matching procedure specifically employed a nearest-neighbour algorithm with a predefined calliper width (0.2 of the standard deviation of the logit of the propensity score). For each exposed subject, we selected the four unexposed subjects with the closest propensity scores within this calliper. The critical ‘with replacement’ aspect meant that after an unexposed subject was selected as a control for a particular exposed subject, that individual remained eligible for selection as a control for other exposed subjects, either within the same wave or in subsequent waves.&lt;/p&gt;&lt;p&gt;From an epidemiological perspective, sampling with replacement in risk set sampling offers several important advantages that enhance study validity [&lt;span&gt;4&lt;/span&gt;]. First, it preserves the representativeness of the control population across all time points in the study. In longitudinal studies where the eligible control pool may fluctuate","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190528","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 10-Year Longitudinal Study of Muscle Morphology and Performance in Masters Sprinters” by Hendrickse et al. – the authors reply","authors":"Paul Hendrickse,&nbsp;Hans Degens","doi":"10.1002/jcsm.70072","DOIUrl":"10.1002/jcsm.70072","url":null,"abstract":"&lt;p&gt;We thank Lin and colleagues [&lt;span&gt;1&lt;/span&gt;] for their interest in our recently published 10-year follow-up study on changes in performance and muscle morphology in masters sprint athletes [&lt;span&gt;2&lt;/span&gt;]. We agree that age-related decrements in mitochondrial capacity correlate with reductions in performance in ageing people and that sleep disruption and endocrine changes, such as a testosterone decline, may underlie the decrease in mitochondrial capacity and exercise performance in ageing.&lt;/p&gt;&lt;p&gt;We contend, however, that impaired mitochondrial function does not directly impact sprint performance or the force output during a maximal isometric contraction as these activities rely on anaerobic, rather than aerobic metabolism [&lt;span&gt;3, 4&lt;/span&gt;]. Although there is no direct link between muscle oxidative capacity and sprint performance, an increased electron flux and leakage from the mitochondrial electron transport chain during ageing could increase oxidative stress in the muscle cells of masters sprinters [&lt;span&gt;5&lt;/span&gt;] that via oxidative modifications of actin and myosin could impair power generation and hence sprint performance [&lt;span&gt;6&lt;/span&gt;]. As it has been reported that regular resistance exercise did not alter the fraction of electrons leaking to reactive oxygen species in the muscle of older people [&lt;span&gt;5&lt;/span&gt;], we suggest that—in spite of regular resistance training—the loss of power and sprint performance we observed over 10 years in masters sprinters is most likely the result of such modifications in myosin and actin and not mitochondrial dysfunction per se [&lt;span&gt;2&lt;/span&gt;]. While sleep deprivation and hypogonadism are detrimental to skeletal muscle health [&lt;span&gt;7, 8&lt;/span&gt;], it is unlikely that they have a direct effect on muscle function and performance.&lt;/p&gt;&lt;p&gt;To illustrate our argument, one could use a thought experiment; if somehow mitochondrial function, sleep disruption and/or low testosterone were rectified in these athletes, it is unlikely that power and sprint performance would recover immediately, whereas if myosin and actin structure were restored, power and performance would likely return even if mitochondrial function, sleep status and/or testosterone levels remained the same. The distinction is that of direct determinants of muscle function and sprint performance (e.g., myofibrillar modifications) from those that precipitate (e.g., hypogonadism, sleep deprivation and mitochondrial dysfunction) poorer muscle function and sprint performance; a distinction between ultimate and proximate causes that is often not recognised.&lt;/p&gt;&lt;p&gt;Therefore, while it is indeed interesting to measure mitochondrial function, hormonal status and sleep quality alongside muscle function in ageing, it adds little to our understanding of what parameters per se affect muscle function in older age. They may, however, be ultimate causes that over time precipitate the proximate cause(s) (e.g., myofibrillar and/or excitation-contraction dysfuncti","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134268","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 “Polygonati Rhizoma Prevents Glucocorticoid-Induced Growth Inhibition of Muscle via Promoting Muscle Angiogenesis Through Deoxycholic Acid” by Shi et al.","authors":"Zhihao Lei","doi":"10.1002/jcsm.70074","DOIUrl":"10.1002/jcsm.70074","url":null,"abstract":"&lt;p&gt;We read with interest the article by Shi et al. [&lt;span&gt;1&lt;/span&gt;], which reports that &lt;i&gt;Polygonati Rhizoma&lt;/i&gt; (PR) extract and a fructose/glucose mixture (MFG) attenuate dexamethasone-induced muscle growth inhibition by promoting “muscle angiogenesis through deoxycholic acid (DCA)” [&lt;span&gt;1&lt;/span&gt;]. While the idea of a gut–muscle axis linking a traditional herbal treatment to muscle perfusion is intriguing, we have significant concerns about the evidence and interpretation. Specifically, the proposed mechanistic chain (PR → gut microbiota → DCA → TGR5 → cAMP/PKA/CREB → VEGF → angiogenesis → muscle growth) is largely speculative, the experiments are underpowered, statistical support is weak, the “active component mimic” MFG is undefined, and correlations are overstated as causation. We outline our main points below.&lt;/p&gt;&lt;p&gt;First, the mechanistic cascade proposed by Shi et al. is inadequately supported. The authors claim MFG “upregulated VEGFs expression and promoted muscle angiogenesis via the TGR5/cAMP/PKA/pCREB pathway” [&lt;span&gt;1&lt;/span&gt;], implying a causal link from gut-derived DCA to muscle VEGF. However, the data are purely correlative. No functional experiments (e.g., DCA supplementation or TGR5 inhibition) were performed to prove any step. Emerging research on the “gut–muscle axis” warns that microbiota-muscle associations are not proof of mechanism. For example, a recent review notes that although gut microbes correlate with sarcopenia risk, “whether the microbiome is the cause of the disease or simply a mediator … is debatable” [&lt;span&gt;2&lt;/span&gt;]. More broadly, microbiome studies are now emphasizing the need to move beyond associations to demonstrate causality [&lt;span&gt;3&lt;/span&gt;]. In Shi et al., PR/MFG treatments were found to raise intestinal DCA and abundance of &lt;i&gt;Collinsella aerofaciens&lt;/i&gt; (&lt;i&gt;p&lt;/i&gt; = 0.096) [&lt;span&gt;1&lt;/span&gt;], and muscle VEGF gene signatures were higher. But without intervening on DCA or TGR5, these observations remain hypothesis-generating at best. As noted by the authors themselves, muscle angiogenesis involves complex, multilevel regulation [&lt;span&gt;1&lt;/span&gt;]; assuming that a change in one bile acid automatically drives the entire VEGF → angiogenesis program is an overreach.&lt;/p&gt;&lt;p&gt;Second, the sample sizes are very small. Key in vivo comparisons involve only &lt;i&gt;n&lt;/i&gt; = 8 (AEPR vs. control), &lt;i&gt;n&lt;/i&gt; = 10 (MFG vs. control), or &lt;i&gt;n&lt;/i&gt; = 7 (DEX vs. DEX + MFG) mice [&lt;span&gt;1&lt;/span&gt;]. Such low &lt;i&gt;n&lt;/i&gt; values are likely underpowered. The ARRIVE guidelines explicitly warn that “sample sizes that are too small … produce inconclusive results” [&lt;span&gt;4&lt;/span&gt;]. Low power not only risks missing real effects but, paradoxically, also inflates the estimated effect size and false positive rate [&lt;span&gt;4, 5&lt;/span&gt;]. Button et al. showed that typical small- N neuroscience studies have very low power, meaning that even “a statistically significant result is less likely to reflect a true effect” [&lt;span&gt;5&lt;/span&gt;]. Shi et al. do not report a","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136063","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 ‘Adherence to Physical Activity and Incident Mobility Disability in Older Adults With Mobility Limitations’ by Alvarez-Bustos et al.","authors":"Yuxia Yang,&nbsp;Meijuan Yuan,&nbsp;Qing Kong,&nbsp;Zhiwei Peng,&nbsp;Yucheng Zhang","doi":"10.1002/jcsm.70071","DOIUrl":"10.1002/jcsm.70071","url":null,"abstract":"<p>While the clinical implications are clear, translating these findings into public health and community-based interventions warrants further exploration. Here, we discuss three actionable dimensions to amplify the societal impact of this research.</p><p>First, Scalable Adherence Monitoring via Digital Health Technologies [<span>1</span>]: The study's categorization of adherence (BR, MR, AR) highlights the critical need for real-time adherence tracking. Wearable sensors (e.g., ActiGraph, Fitbit) and AI-driven platforms can objectively monitor PA frequency, intensity and duration in community settings. For instance, remote coaching apps with automated feedback loops, similar to the SPRINTT trial's technological support, could personalize adherence goals based on baseline SPPB scores. Integrating such tools into existing community health programmes (e.g., the WHO's Integrated Care for Older People, ICOPE) would democratize access, particularly in rural or resource-limited areas [<span>1</span>].</p><p>Second, Community Health Workers as Adherence Facilitators [<span>2</span>]: Participants with SPPB 3–7 benefitted most from &gt; 3 sessions/week, yet sustaining high adherence remains challenging. Task-shifting to community health workers (CHWs) could bridge this gap. CHWs trained in geriatric exercise protocols can conduct home visits, deliver nutritional counselling and foster social accountability through peer-support groups. Embedding CHWs within primary care networks would operationalize the study's adherence framework while addressing socioeconomic barriers [<span>2</span>].</p><p>Third, Policy Integration Regarding Reimbursement and Infrastructure: The differential benefit of AR adherence (HR: 0.33 for SPPB 3–7) underscores the need for policy-level changes. Medicare's current reimbursement for ‘exercise as medicine’ is limited to cardiac rehabilitation. Expanding coverage to include multimodal PA programmes for PF&amp;S—with incentives tied to adherence metrics—would incentivize healthcare systems to adopt SPRINTT-like interventions [<span>3</span>]. Concurrently, investing in public infrastructure (e.g., safe walking paths, subsidized community gyms) could reduce environmental barriers to adherence, aligning with the WHO's ‘Decade of Healthy Ageing’ goals.</p><p>In conclusion, Alvarez-Bustos et al.'s work provides a robust template for combating mobility disability. By leveraging digital tools, community networks and policy reform, we can transform adherence from a clinical variable into a public health priority.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136031","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":"Comorbidity and Malnutrition as Key Determinants of Mortality in Elderly Haemodialysis Patients: A One-Year Observational Study","authors":"M. L. Sanchez-Tocino,&nbsp;S. Mas-Fontao,&nbsp;E. González-Parra,&nbsp;P. Manso,&nbsp;M. Burgos,&nbsp;D. Carneiro,&nbsp;M. Pereira,&nbsp;C. Pereira,&nbsp;A. Lopez-González,&nbsp;M. D. Arenas,&nbsp;on behalf the renal foundation work team","doi":"10.1002/jcsm.70062","DOIUrl":"10.1002/jcsm.70062","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;In elderly haemodialysis patients, poor functional status correlates with malnutrition, morbidity and mortality. This study aimed to assess 1-year survival in an elderly haemodialysis population and evaluate the predictive capacity of commonly used scales for comorbidity, malnutrition, dependence and frailty.&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 conducted a 1-year observational study (2022) on prevalent haemodialysis patients aged &gt; 75 years with &gt; 3 months of treatment. Mortality was assessed during the follow-up. We analysed sociodemographic, dialysis-related, analytical and lifestyle variables. Additionally, we evaluated comorbidity (Charlson), dependence (Barthel), malnutrition-inflammation (MIS scale) and frailty (FRIED). Statistical analysis included comparisons between continuous variables using the Mann–Whitney &lt;i&gt;U&lt;/i&gt; test or Student's &lt;i&gt;t&lt;/i&gt; test, based on normality distribution. Categorical variables were compared using the chi-square test. Kaplan–Meier survival analysis with log-rank test was used to compare survival curves. Multivariate analysis was performed using Cox proportional hazards models, adjusting for confounders including dialysis adequacy and underlying kidney disease aetiology. Optimal cutoff points for predicting mortality were determined using receiver operating characteristic (ROC) curves.&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 107 haemodialysis patients (57% male, mean age 81.3 ± 4.53 years, mean time on haemodialysis 51.71 ± 51.04 months) were included. Sixteen patients (15%) died within 1 year. Deceased patients were older (83.94 ± 4.52 vs. 80.34 ± 4.39 years, &lt;i&gt;p&lt;/i&gt; = 0.011) and had longer dialysis duration (76.46 ± 54.73 vs. 47.35 ± 49.4 months, &lt;i&gt;p&lt;/i&gt; = 0.035), lower albumin (3.51 ± 0.54 vs. 3.86 ± 0.31 g/dL, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and lower creatinine levels (5.48 ± 1.12 vs. 6.50 ± 1.67 mg/dL, &lt;i&gt;p&lt;/i&gt; = 0.021). They scored higher on all four scales analysed: Charlson (10.94 ± 1.81 vs. 8.95 ± 1.92, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), MIS (11.31 ± 4.22 vs. 6.07 ± 3.27, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), Barthel (52.50 ± 27.2 vs. 78.41 ± 23.11, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and FRIED (3.19 ± 1.05 vs. 2.18 ± 1.32, &lt;i&gt;p&lt;/i&gt; = 0.005). Institutionalization (&lt;i&gt;p&lt;/i&gt; = 0.004), inability to walk (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and stretcher transport (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) were also significantly associated with mortality. The optimal cutoff points for predicting mortality were Charlson index ≥ 9.5 (AUC 0.788, 95% CI: 0.65–0.88), MIS ≥ 7.5 (AUC 0.844, 95% CI: 0.73–0.93), Barthel ≤ 67.5 (AUC 0.79, 95% CI: 0.68–0.79) and FRIED ≥ 2.5 (AUC 0.719, 95% CI: 0.56–0.83). In multivariable analysi","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127092","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 ‘Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoint Series’ by Dajani et al.—The Authors' Reply","authors":"Jann Arends,&nbsp;Olav Dajani,&nbsp;Iain Philips,&nbsp;Richard J. E. Skipworth,&nbsp;Tora S. Solheim,&nbsp;Barry J. A. Laird","doi":"10.1002/jcsm.70069","DOIUrl":"10.1002/jcsm.70069","url":null,"abstract":"&lt;p&gt;Cancer cachexia may be interpreted as a battle of an organism against a chronic attack on its integrity, resulting in a complex and potentially oscillating evolution of pathophysiological and clinical signs and symptoms. The apparent heterogeneity and variability of this syndrome so far have impeded the development of effective interventions and even precluded an agreement on the most important targets to monitor. The cachexia endpoint series was initiated to screen and search the evidence accumulated in randomized controlled anti-cachexia trials aiming to compare the type and value of different outcome parameters [&lt;span&gt;1-6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The analysis of oncological endpoints yielded a large heterogeneity in target populations, interventions and trial designs [&lt;span&gt;2&lt;/span&gt;]. This, a prevalent lack of statistical rigour and the rarity of positive findings, prevented valid comparisons of interventions and endpoints. Importantly, only two out of 57 trials reported significant effects on a primary oncological outcome [&lt;span&gt;7, 8&lt;/span&gt;], and due to statistical issues, both results need to be interpreted as exploratory.&lt;/p&gt;&lt;p&gt;We are thankful for the comments added to our findings by Kumar et al., which excellently amend our suggestions for the design of future anti-cachexia trials [&lt;span&gt;9&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The deleterious effects of weight loss, sarcopenia and systemic inflammation on oncological outcomes are well known and observable in curative and palliative settings [&lt;span&gt;10-15&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;However, there is little information on whether anti-cachexia interventions are more effective in mild or more severe activity of the cachexia syndrome [&lt;span&gt;16, 17&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Kumar et al. allude to the potential effect of combining or sequencing anti-cachexia and anti-cancer strategies [&lt;span&gt;9&lt;/span&gt;]. In our analysis of 57 trials [&lt;span&gt;2&lt;/span&gt;], there were only combined treatments, but none in sequence. However, when considering a treatment sequence, it may both appear suboptimal to delay oncological therapy while waiting for an anti-cachexia effect or to delay cachexia treatment until completing the oncological intervention. Another option would be interspersing anti-cachexia and anti-cancer activities.&lt;/p&gt;&lt;p&gt;Symptoms of cachexia are of prime relevance to the diseased subjects, and drug approval agencies increasingly require documentation of improvement in patient-reported outcomes (PRO) [&lt;span&gt;18&lt;/span&gt;]. In fact, PRO are covered extensively in our endpoint series by Hjermstad et al. [&lt;span&gt;3&lt;/span&gt;]. Due to a lack of respective data, analysing interactions between oncological endpoints and PROs was not possible in our review [&lt;span&gt;2&lt;/span&gt;] and thus needs to be positioned as an important goal for newly designed trials.&lt;/p&gt;&lt;p&gt;Finally, we agree that when considering treatment options for cancer cachexia, the socioeconomic background is of major importance on a local and especially on a global scale. We thus urge to aim for low-cost and easily","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133999","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.—The Authors' Reply","authors":"Qian Ren,&nbsp;Jinrong Liang,&nbsp;Yanmei Su,&nbsp;Ruijing Tian,&nbsp;Junxian Wu,&nbsp;Sheng Ge,&nbsp;Peizhan Chen","doi":"10.1002/jcsm.70067","DOIUrl":"10.1002/jcsm.70067","url":null,"abstract":"&lt;p&gt;We would like to thank Zeng et al. [&lt;span&gt;1&lt;/span&gt;] and Zheng et al. [&lt;span&gt;2&lt;/span&gt;] for their comments on our recently published manuscript suggesting that serum 25(OH)D level may be causally associated with the appendicular muscle mass (AMM) [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We concur with Zeng et al. [&lt;span&gt;1&lt;/span&gt;] and Zheng et al. [&lt;span&gt;2&lt;/span&gt;] that sample overlap in Mendelian Randomization (MR) analyses may introduce potential bias and increase type I error rates, a concern that has been extensively documented in methodological studies of MR [&lt;span&gt;4, 5&lt;/span&gt;]. Nowadays, genome-wide association studies (GWASs) consortium usually integrate numerous large datasets for meta-analysis [&lt;span&gt;4&lt;/span&gt;]. In two-sample MR studies, complete sample non-overlap cannot always be guaranteed, as large GWAS consortium summary statistics are now commonly employed as both instrumental variables for exposures and for outcome associations in MR analyses [&lt;span&gt;4&lt;/span&gt;]. We noticed that recently published two-sample MR studies typically had a high or low proportion of overlapped samples even in these well-designed investigations [&lt;span&gt;6-8&lt;/span&gt;]. In our study, we noticed a significant association between serum 25(OH)D level and AMM in the NHANES dataset with a large sample size (&lt;i&gt;n&lt;/i&gt; = 11 242) [&lt;span&gt;3&lt;/span&gt;]. We would like to assess whether there is a causal relationship between 25(OH)D level and AMM. Revez et al. performed the GWAS on serum 25(OH)D levels in UK Biobank participants (&lt;i&gt;n&lt;/i&gt; = 417 580), identifying 143 independent loci that were significantly associated with serum 25(OH)D [&lt;span&gt;9&lt;/span&gt;]. This study, which provided the most complete data in the IEU OpenGWAS database (ebi-a-GCST90000617), was used to extract IVs for serum 25(OH)D level in MR studies. To our best knowledge, only one large-scale GWAS on AMM (&lt;i&gt;n&lt;/i&gt; = 450 243) has been conducted to date, performed by Pei et al. [&lt;span&gt;10&lt;/span&gt;] in UK Biobank participants. Using summary statistics from these two GWASs on serum 25(OH)D and AMM, we conducted the two-sample MR analysis to assess their causal relationship, though the sample overlap was unavoidable.&lt;/p&gt;&lt;p&gt;According to recommendation by Zeng et al. [&lt;span&gt;1&lt;/span&gt;], we assessed the magnitude of bias and control for inflated type I error rates using the online tools (https://sb452.shinyapps.io/overlap) as previously described [&lt;span&gt;5&lt;/span&gt;]. We found the bias was estimated to be 0.001 with the type I error rate being 0.05, suggesting minimal influences caused by sample overlap in the MR studies. We also applied the MRlap method, which was designed to correct the joint biases caused by the Winner's curse, to assess the causal association between serum 25(OH)D level and AMM [&lt;span&gt;4&lt;/span&gt;]. The MRlap algorithm calculates a test statistic to evaluate whether the corrected effect estimate is significantly different from the inverse variance weighted (IVW)-MR observed effect. If there is no significant difference, the observed ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127343","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}