Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse","authors":"Marie E. Esper, Caroline E. Brun, Alexander Y. T. Lin, Peter Feige, Marie J. Catenacci, Marie-Claude Sincennes, Morten Ritso, Michael A. Rudnicki","doi":"10.1002/jcsm.13682","DOIUrl":"10.1002/jcsm.13682","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the <i>mdx</i> mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays. We examined the architectural and functional changes in <i>mdx</i> skeletal muscle from 13 and 52 weeks of age and following acute cardiotoxin (CTX) injury. We also studied MuSC dynamics and function under homeostatic conditions, during regeneration post-acute injury, and following engraftment using a combination of histological and transcriptomic analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dystrophin-deficient skeletal muscle undergoes progressive changes with age and delayed regeneration in response to acute injury. Muscle hypertrophy, deposition of collagen and an increase in small myofibres occur with age in the <i>tibialis anterior</i> (TA) and diaphragm muscles in <i>mdx</i> mice. Dystrophic <i>mdx</i> mouse TA muscles become hypertrophic with age, whereas diaphragm atrophy is evident in 1-year-old <i>mdx</i> mice. Maximum tetanic force is comparable between genotypes in the TA, but maximum specific force is reduced by up to 38% between 13 and 52 weeks in the <i>mdx</i> mouse. Following acute injury, myofibre hyperplasia and hypotrophy and delayed recovery of maximum tetanic force occur in the <i>mdx</i> TA. We also find defective MuSC polarity and reduced numbers of myocytes in <i>mdx</i> muscle following acute injury. We observed a 50% and 30% decrease in PAX7<sup>+</sup> and MYOG<sup>+</sup> cells, respectively, at 5 days post CTX injury (5 dpi) in the <i>mdx</i> TA. A similar decrease in <i>mdx</i> progenitor cell proportion is observed by single cell RNA sequencing of myogenic cells at 5 dpi. The global expression of commitment-related genes is also reduced at 5 dpi. We find a 46% reduction in polarized PARD3 in <i>mdx</i> MuSCs. Finally, <i>mdx</i> MuSCs exhibit elevated PAX7<sup>+</sup> cell engraftment with significantly fewer donor-derived myonuclei in regenerated myofibres.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study provides evidence that dystrophin de","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886946","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":"Correction to ‘Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis’","authors":"","doi":"10.1002/jcsm.13687","DOIUrl":"10.1002/jcsm.13687","url":null,"abstract":"<p>Arneson-Wissink P. C., Mendez H., Pelz K., Dickie J., Bartlett A. Q., Worley B. L., et al (2024) Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis, <i>Journal of Cachexia, Sarcopenia and Muscle</i>. https://doi.org/10.1002/jcsm.13466.</p><p>In our attribution of funding, we mistakenly omitted the following: PCAW was supported by the National Cancer Institute K99CA286709–01.</p><p>We apologize for this error.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886944","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 ‘Artificial Neural Network Inference Analysis Identified Novel Genes and Gene Interactions Associated With Skeletal Muscle Aging’ by Tarum et al.","authors":"Jing-Lu Zheng,&nbsp;Xi-Yang Chen,&nbsp;Yi-Kai Li,&nbsp;Hong-Wen Liu","doi":"10.1002/jcsm.13680","DOIUrl":"10.1002/jcsm.13680","url":null,"abstract":"&lt;p&gt;We read with great interest the recent article by Tarum et al. [&lt;span&gt;1&lt;/span&gt;], titled ‘Artificial Neural Network Inference Analysis Identified Novel Genes and Gene Interactions Associated With Skeletal Muscle Aging’. This study introduces an innovative application of artificial neural network inference (ANNi) to elucidate complex gene networks implicated in skeletal muscle ageing. The findings provide significant insights that hold potential for advancing sarcopenia research and guiding targeted interventions. The novel application of ANNi in this context and the compelling results underscore the valuable role computational methods can play in exploring age-related diseases and identifying new therapeutic targets.&lt;/p&gt;&lt;p&gt;The critical contribution of this study lies in its utilization of ANNi to reveal intricate relationships among genes associated with muscle ageing, specifically identifying CHAD, ZDBF2 and USP54 as central genes. This deep learning–based analysis is precious, as it extends beyond traditional statistical methods to detect subtle gene–gene interactions that may remain hidden in conventional analyses. Through ANNi, the authors ranked genes by their interaction strength, revealing CHAD and ZDBF2 as highly interactive targets within ageing muscle networks, while USP54 emerged as a significant regulator. USP54's role in the ubiquitin–proteasome system, a pathway critical in muscle atrophy, reinforces its relevance as a potential therapeutic target for sarcopenia.&lt;/p&gt;&lt;p&gt;The study's findings provide a more detailed understanding of sarcopenia's molecular landscape. Given the links between age-related muscle atrophy, heightened catabolic activity, systemic inflammation and oxidative stress, discovering new gene networks provides insights that may eventually inform pharmacological and non-pharmacological interventions. Tarum et al. effectively demonstrate that ANNi, by examining gene interaction networks rather than focusing solely on differential gene expression, can reveal complex molecular interplay that drives muscle ageing. This perspective allows for a more comprehensive understanding of sarcopenia's pathogenesis, potentially guiding more targeted therapeutic strategies aimed at modulating these interactions to slow or reverse muscle degeneration.&lt;/p&gt;&lt;p&gt;While the study provides valuable insights, there are several areas where additional exploration could further enrich these findings. Although the authors validate gene expression changes through qPCR, assessing how genes like CHAD, ZDBF2 and USP54 express across different stages of sarcopenia would be informative. Understanding whether these genes maintain consistent expression levels throughout muscle ageing or if expression varies across early, mid and late stages could shed light on their roles in sarcopenia progression. Such stage-based analysis could also reveal time points where therapeutic interventions have maximal impact.&lt;/p&gt;&lt;p&gt;The study also investigates resistance tra","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886947","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":"NLRP3 Inflammasome Activation and Altered Mitophagy Are Key Pathways in Inclusion Body Myositis","authors":"Elie Naddaf,&nbsp;Thi Kim Oanh Nguyen,&nbsp;Jens O. Watzlawik,&nbsp;Huanyao Gao,&nbsp;Xu Hou,&nbsp;Fabienne C. Fiesel,&nbsp;Jay Mandrekar,&nbsp;Eileen Kokesh,&nbsp;William S. Harmsen,&nbsp;Ian R. Lanza,&nbsp;Wolfdieter Springer,&nbsp;Eugenia Trushina","doi":"10.1002/jcsm.13672","DOIUrl":"10.1002/jcsm.13672","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;Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. In this study, we aimed to explore the interplay between inflammation and mitochondrial dysfunction in IBM.&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;The study population consisted of 38 IBM patients and 22 age- and sex-matched controls without a myopathy. Mean age was 62.9 years (SD = 9) in IBM group and 59.7 (10) in controls. Bulk RNA sequencing, Meso Scale Discovery electrochemiluminescence (ECL), western blotting, histochemistry and immunohistochemistry were performed on frozen muscle samples from the study participants.&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;We demonstrated activation of the NLRP3 inflammasome in IBM muscle samples, with the NLRP3 inflammasome being the most upregulated pathway on RNA sequencing, along with increased expression of NLRP3 and ASC proteins in IBM group. &lt;i&gt;NLRP3&lt;/i&gt; RNA levels most strongly correlated with &lt;i&gt;TLR7&lt;/i&gt; (correlation coefficient &lt;i&gt;ρ&lt;/i&gt; = 0.91) and complement activation-related genes, and inversely correlated with several mitochondria-related genes among others. On muscle histopathology, there was increased NRLP3 immunoreactivity in both inflammatory cells and muscle fibres. Mitophagy is critical for removing damaged mitochondria and preventing the formation of a vicious cycle of mitochondrial dysfunction—NLRP3 inflammasome activation. Herein, we showed altered mitophagy, as witnessed by the elevated levels of p-S65-Ubiquitin, a mitophagy marker, in muscle lysates from IBM patients compared to controls (median of 114.3 vs. 81.25 ECL units, &lt;i&gt;p&lt;/i&gt; = 0.005). The p-S65-Ubiquitin levels were most significantly elevated in IBM males compared to male controls (136 vs. 83.5 ECL units; &lt;i&gt;p&lt;/i&gt; = 0.013), whereas IBM females had milder nonsignificant elevation compared to female controls (97.25 vs. 69 ECL units, &lt;i&gt;p&lt;/i&gt; = 0.31). On muscle histopathology, p-S65-Ubiquitin aggregates accumulated in muscle fibres that were mostly Type 2 and devoid of cytochrome-c-oxidase reactivity. &lt;i&gt;NLRP3 RNA&lt;/i&gt; levels correlated with p-S65-Ubiquitin levels in both sexes (males: &lt;i&gt;ρ&lt;/i&gt; = 0.48, females: &lt;i&gt;ρ&lt;/i&gt; = 0.54) but with loss of muscle strength, as reflected by the manual motor test score, only in males (males: &lt;i&gt;ρ&lt;/i&gt; = 0.62, females: &lt;i&gt;ρ&lt;/i&gt; = −0.14). Lastly, we identified sex-specific molecular pathways in IBM. Females had upregulation of pathways related to response to stress, which could conceivably offset some of the pathomechanisms of IBM, while males had upregulation of pathways related to c","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886948","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":"Distinct Gut Microbiota Profiles in Normal Weight Obesity and Their Association With Cardiometabolic Diseases: Results From Two Independent Cohort Studies","authors":"Wenjie Wang,&nbsp;Feijie Wang,&nbsp;Yihan Li,&nbsp;Yuwei Shi,&nbsp;Xiaoyan Wang,&nbsp;Xinyu Chen,&nbsp;Weifang Zheng,&nbsp;Julianna C. Hsing,&nbsp;Ying Lu,&nbsp;Yi-Shuan Wu,&nbsp;Ann W. Hsing,&nbsp;Juntao Kan,&nbsp;Wei He,&nbsp;Shankuan Zhu","doi":"10.1002/jcsm.13644","DOIUrl":"10.1002/jcsm.13644","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;Normal weight obesity (NWO) is characterized by excess body fat in individuals with normal body mass index (BMI). This study aimed to investigate gut microbiota alterations in NWO and their potential associations with cardiometabolic diseases (CMD) risk in two independent cohorts.&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;Our NWO-CMD mortality analysis included 168 099 adults with normal BMI from two large open-access databases, while our NWO-gut microbiota study involved 5467 adults with normal BMI from two independent cohorts: the WELL-China cohort and the Lanxi cohort. NWO was defined as having a normal BMI (18.5–23.9 kg/m&lt;sup&gt;2&lt;/sup&gt;) but an excess per cent body fat (PBF, ≥ 25% in men and ≥ 35% in women). Normal weight lean was defined as having a normal BMI and normal PBF. The 16S rRNA gene sequencing method was used to analyse gut microbiota data.&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 study comprised 3620 (64.0% female, median age 58 years) and 1847 (64.3% female, median age 56 years) participants from the WELL-China and Lanxi cohorts. In our meta-analysis, NWO is associated with 26% (95% CI: 1.07–1.41) higher risk of CMD mortality. Gut microbial analyses indicated that the NWO group exhibited reduced levels of observed species (&lt;i&gt;p&lt;/i&gt; = 0.009 and &lt;i&gt;p&lt;/i&gt; = 0.013) and Chao 1 index (&lt;i&gt;p&lt;/i&gt; = 0.002 and &lt;i&gt;p&lt;/i&gt; = 0.002) and altered gut microbial compositions (&lt;i&gt;p&lt;/i&gt; = 0.009 and &lt;i&gt;p&lt;/i&gt; &lt; 0.001) compared with the NWL group. Seven genera were consistently observed to be associated with NWO in both two cohorts (all Q &lt; 0.25). Among them, five (&lt;i&gt;Fusobacterium&lt;/i&gt;, &lt;i&gt;Ruminococcus gnavus group&lt;/i&gt;, &lt;i&gt;Ruminococcus torques group&lt;/i&gt;, &lt;i&gt;Coprococcus&lt;/i&gt; and &lt;i&gt;Christensenellaceae_R7_group&lt;/i&gt;) have been previously linked to obesity, while the other two (&lt;i&gt;Phascolarctobacterium&lt;/i&gt; and &lt;i&gt;Clostridia_UCG-014&lt;/i&gt;) were minimally reported. We also found statistically significant differences in the microbial composition between the NWO group and the obesity group (&lt;i&gt;p&lt;/i&gt; = 0.001 and &lt;i&gt;p&lt;/i&gt; = 0.001). Furthermore, the NWO-related gut microbiome was associated with an elevated risk of hypertension, dyslipidaemia and metabolic syndrome, the corresponding HR (95% CIs) were 1.11 (1.01–1.22), 1.19 (1.10–1.29) and 1.17 (1.05–1.30) in the WELL-China cohort and 1.14 (1.02–1.27), 1.15 (1.02–1.29) and 1.16 (1.02–1.32) in the Lanxi cohort.&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;These two large cohorts provided reliable evidence that gut microbiota alterations in NWO resemble those f","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13644","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886950","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":"Comparison Between Single- and Multi-slice Computed Tomography Body Composition Analysis in Patients With Oesophagogastric Cancer","authors":"Leo R. Brown,&nbsp;Maria Soupashi,&nbsp;Michael S. Yule,&nbsp;Danielle R. Clyde,&nbsp;Ellen Gardner,&nbsp;Charlotte Smith,&nbsp;Ahmed Dhaif,&nbsp;Barry J. A. Laird,&nbsp;Stephen J. Wigmore,&nbsp;Richard J. E. Skipworth","doi":"10.1002/jcsm.13673","DOIUrl":"10.1002/jcsm.13673","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;Single-slice computed tomography (CT) body composition has been studied extensively for prognostication in patients with cancer. New software packages can also provide multi-slice volumetric measurements, but the clinical utility of these remains under explored. This study aimed to evaluate the agreement between single- and multi-slice body composition analyses in patients with oesophagogastric cancer and to explore the association between these measures and overall survival.&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;Consecutive patients with newly diagnosed oesophagogastric (OG) cancer were identified through the prospectively maintained regional database of the South East Scotland Cancer Network across a 2-year study period. CT body composition analyses were undertaken using scans collected during routine clinical care. Single-slice (cross-sectional area at mid L3) and multi-slice (volume between T12 and L4) measurements were compared for skeletal muscle (SKM), subcutaneous adipose (SAT), visceral adipose (VAT) and intermuscular adipose (IMAT). Agreement between sex-stratified z-scores was quantified using Pearson correlation coefficients and Bland–Altman analyses. Cox proportional hazard modelling was used to estimate the effect of these measures on overall survival.&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;Overall, 504 patients (67.9% male, median 72 years) were newly diagnosed with OG cancer during the study period. Single- and multi-slice (mean: 169 slices) measurements correlated highly for SKM (R: 0.97, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), SAT (R: 0.98, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), VAT (R: 0.97, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), SKM radiodensity (R: 0.93, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and IMAT (R: 0.88, p &lt; 0.001). Bias on Bland–Altman analysis was 0.00 for all tissue measurements. Limits of agreement (LoA) were narrowest for SAT (±0.43), VAT (±0.46) and SKM (±0.48), but slightly wider for SKM radiodensity (±0.73) and IMAT (±0.96). Adipose tissue ‘outliers’ (those where agreement between single- and multi-slice z-scores was outside the LoA) had a higher median weight and body mass index (BMI), suggestive of poorer agreement in patients with obesity. Sensitivity analysis, excluding those with BMI &gt; 30, narrowed the LoA for SKM, VAT, SAT and IMAT. Direction and magnitudes of observed effect sizes for overall survival were all highly comparable, with hazard ratios for each tissue type varying by ≤ 0.04 between single- and multi-slice adjusted estimates.&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;Single-slice and multi-slice ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886943","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":"Anorexia of Ageing, an Underappreciated Perioperative Concern?","authors":"Brandon Stretton,&nbsp;Joshua Kovoor,&nbsp;Aashray Gupta,&nbsp;Stephen Bacchi","doi":"10.1002/jcsm.13683","DOIUrl":"10.1002/jcsm.13683","url":null,"abstract":"&lt;p&gt;Between early 2000 and 2050, the number of people aged &gt; 60 is expected to double, approaching 22% in developed regions [&lt;span&gt;1&lt;/span&gt;]. As half of the population aged over 65 will require surgery at some point, reducing operative burden, particularly in the elderly, is a major public health concern [&lt;span&gt;2&lt;/span&gt;]. One such age-related change that was first described in 1994, which is yet to receive the recognition for its perioperative implications, is the alteration in the ability to accurately control energy intake and energy balance, ‘anorexia of ageing’ [&lt;span&gt;3&lt;/span&gt;]. The incidence of this clinical syndrome is climbing alongside the ageing population; however, despite its high prevalence, it is often overlooked by clinicians [&lt;span&gt;4, 5&lt;/span&gt;]. How this geriatric syndrome influences perioperative outcomes however remains unclear and requires further clarification through both clinical evaluation and research. This letter aims to provide a clear roadmap for addressing this underappreciated concern and encourage further investigation by defining the anorexia of ageing and discussing how the multifactorial aspects of anorexia of ageing may interface with the perioperative patient and their outcomes, as well as possible empiric management options.&lt;/p&gt;&lt;p&gt;Anorexia of ageing is a geriatric syndrome that is defined by decrease in energy intake, and the reduction in appetite that underlies it, with associated undernutrition, unintended weight loss, immunocompromise/senescence, frailty and by association, sarcopenia, functional impairment, loss of independence and quality of life, alongside other adverse health outcomes [&lt;span&gt;6&lt;/span&gt;]. Energy intake decreases by ~30% between the ages of 20 and 80, with elderly tending to consume smaller, less frequent meals more slowly and overall, be less hungry, with more rapid satiation than young adults [&lt;span&gt;7&lt;/span&gt;]. It is a common syndrome, affecting up to 25% of community dwellers and 85% of aged care facility clients [&lt;span&gt;8&lt;/span&gt;]. It is characterised by a multifactorial process involving physical, societal and physiological factors.&lt;/p&gt;&lt;p&gt;Age-related functional impairments (such as immobility, visual decline, poor dentition and neurocognitive impairment) can impair a person's ability to shop, prepare and consume food and are associated with poor protein intake [&lt;span&gt;7&lt;/span&gt;]. Societal factors such as financial limitations and loneliness also contribute to reduced oral intake by precluding access to nutrition and decreasing appetite, with elderly people consuming up to 50% more in the company of friends compared to eating alone [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;There are also physiological changes that contribute to the anorexia of ageing, with changes in homeostatic mechanisms, neurotransmitter/hormonal function and the alimentary tract. Homeostasis of energy intake is impaired in the elderly. When a caloric restriction is imposed on elderly individuals, they do not demonstrate the same compensat","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886949","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":"CT-Based Body Composition and Frailty as Predictors of Survival Among Older Adults With Gastrointestinal Malignancies","authors":"Smith Giri,&nbsp;Christian Harmon,&nbsp;Daniel Hess,&nbsp;Elizabeth M. Cespedes Feliciano,&nbsp;Ijeamaka Anyene Fumagalli,&nbsp;Bette Caan,&nbsp;Leon Lenchik,&nbsp;Karteek Popuri,&nbsp;Vincent Chow,&nbsp;Mirza Faisal Beg,&nbsp;Smita Bhatia,&nbsp;Grant R. Williams","doi":"10.1002/jcsm.13664","DOIUrl":"10.1002/jcsm.13664","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Older adults with cancer are at an increased risk of treatment related toxicities and early death. Routinely collected clinico-demographic characteristics inadequately explain this increased risk limiting accurate prognostication. Prior studies have suggested that altered body composition and frailty are independently associated with worse survival among older adults with cancer; however, their combined influence remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from a single-institution prospective cohort study of older adults (≥ 60 years) who underwent geriatric assessment (GA) at the time of initial consultation with a medical oncologist from September 2017 to December 2020 and available baseline abdominal computed tomography within 60 days of GA. Using multi-slice CT images from T12 to L5 level, we assessed volumetric measures of skeletal muscle (SMV), visceral adipose tissue (VATV), subcutaneous adipose tissue (SATV) and averaged skeletal muscle density (SMD), computing sex-specific <i>z</i> for each measure. Frailty was measured using a 44-item frailty index using the deficit accumulation approach. Primary outcome of interest was overall survival (OS) defined as time from GA to death or last follow up. We used multivariable Cox regression model to study the independent association between the above four body composition measurements and OS adjusted for baseline confounders and frailty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 459 patients with a mean age of 69.7 ± 7.5 years, 60% males and 77% non-Hispanic Whites. Most had colorectal (27%) or pancreatic cancer (20%) and 48% had stage IV disease. Over a median follow up of 39.4 months, 209 patients (46%) died. In multivariable Cox regression models adjusted for age, sex, race, cancer type, cancer stage and frailty, skeletal muscle volume (HR 0.74; 95% CI 0.58–0.96; <i>p</i> = 0.02, per 1 SD increment) was independently associated with OS. The addition of body composition variables to baseline clinico-demographic variables and frailty led to a slightly improved model discrimination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SMV is independently associated with OS among older adults with newly diagnosed gastrointestinal cancers. Capturing body composition measurements in oncology practice may provide additional prognostic information for older adults with cancer above and beyond what is captured in routine clinical assessment including frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873943","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 ‘Association of Computed Tomography-Derived Body Composition and Complications After Colorectal Cancer Surgery: A Systematic Review and Meta-Analysis’ by Van Helsdingen et al.","authors":"Rachana Mehta,&nbsp;Ashok Kumar Balaraman,&nbsp;Muhammed Shabil,&nbsp;Sanjit Sah","doi":"10.1002/jcsm.13679","DOIUrl":"10.1002/jcsm.13679","url":null,"abstract":"&lt;p&gt;We read with great interest the article titled ‘Association of computed tomography-derived body composition and complications after colorectal cancer surgery A systematic review and meta-analysis’ and commend the authors for their rigorous and insightful systematic review and meta-analysis on body composition measurements using computed tomography (CT) scans as predictors of complications following colorectal cancer surgery [&lt;span&gt;1&lt;/span&gt;]. This research addresses a highly relevant clinical issue, providing valuable information to guide surgical decision-making. While the article provides important findings, we believe there are some additional aspects that could further strengthen its impact and provide readers with an even more comprehensive understanding.&lt;/p&gt;&lt;p&gt;First, although the authors conducted a thorough risk of bias assessment using the QUIPS tool, the article does not mention whether a sensitivity analysis was performed based on study quality. We suggest conducting such an analysis to examine how excluding lower-quality studies (e.g., those rated as having a high risk of bias) may impact the pooled results. Sensitivity analysis could help readers better appreciate the robustness of the findings and determine whether the conclusions are consistent across studies with varying levels of methodological rigour [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Second, the certainty of evidence presented in this study could have been evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework. GRADE is widely recognized for systematically assessing the quality of evidence and the strength of recommendations in health care research. Including a GRADE assessment would allow the readers to understand the confidence in the results across different outcomes, especially given the variability in CT measurement methods and clinical endpoints considered in the studies [&lt;span&gt;3&lt;/span&gt;]. This would also facilitate the translation of evidence into clinical practice by offering clarity on the reliability of the conclusions.&lt;/p&gt;&lt;p&gt;Third, while the authors rightfully address the risk of publication bias in the discussion, we recommend the inclusion of formal statistical methods to assess this risk. A funnel plot or DOI plot, alongside statistical tests such as Egger's regression or the trim-and-fill method, could provide more concrete evidence of the presence or absence of publication bias [&lt;span&gt;4&lt;/span&gt;]. These methods would further substantiate the robustness of the meta-analytic findings by ensuring that the results were not disproportionately influenced by small or positive-result studies.&lt;/p&gt;&lt;p&gt;Furthermore, it might be valuable to explore subgroup analyses based on factors such as the specific CT measurement (e.g., visceral fat vs. sarcopenia), patient age, or cancer stage. These analyses could uncover potential variations in predictive utility across different patient populations, making the results more clinically actionable. ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873941","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 ‘Association Between Dynapenic Obesity and Risk of Cardiovascular Disease: The Hisayama Study’ by Setoyama et al.","authors":"Chang Liu,&nbsp;Fan Zhang,&nbsp;Min Cao","doi":"10.1002/jcsm.13684","DOIUrl":"10.1002/jcsm.13684","url":null,"abstract":"&lt;p&gt;We have read with interest the article by Setoyama Y et al. [&lt;span&gt;1&lt;/span&gt;] titled ‘Association of dynapenic obesity with cardiovascular disease: The Hisayama Study.’ While this study provides valuable insights into the relationship between dynapenic obesity and cardiovascular disease risk, we would like to highlight three points that warrant further discussion.&lt;/p&gt;&lt;p&gt;First, the authors introduce the concept of ‘dynapenic obesity’ and discuss it alongside ‘sarcopenic obesity’ in the introduction, citing multiple references related to sarcopenic obesity. However, according to the 2022 guidelines from the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO), sarcopenic obesity is specifically defined as the coexistence of obesity and sarcopenia [&lt;span&gt;2&lt;/span&gt;]. In Setoyama et al.'s study, dynapenic obesity only considers handgrip strength and body mass index, whereas handgrip strength is just one dimension of assessing sarcopenia and cannot fully represent a sarcopenia diagnosis [&lt;span&gt;3&lt;/span&gt;]. Therefore, the authors should not equate dynapenic obesity with sarcopenic obesity. This conceptual confusion may lead to misinterpretation and misapplication of the study results.&lt;/p&gt;&lt;p&gt;Second, this study not only spans a median follow-up of 24 years but also assesses baseline handgrip strength and body mass index. Over such an extended follow-up period, important variables such as participants' physical function, height, weight, dietary habits, and physical activity are likely to have changed significantly. These changes would inevitably affect the association between exposure and outcome, and we consider this crucial limitation should be emphasized more strongly, with a discussion of its potential impact on the study findings.&lt;/p&gt;&lt;p&gt;Third, from a statistical perspective, the study uses Cox proportional hazards models to analyse the relationship between dynapenic obesity and cardiovascular disease risk. However, given the long-term nature of the follow-up, the proportional hazards assumption may not hold. The impact of dynapenic obesity on cardiovascular disease risk might change over time. Therefore, we suggest that the authors consider using time-dependent Cox models or other statistical methods suitable for long-term follow-up data to more accurately capture the time-varying relationship between exposure and outcome [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Additionally, the study employs multiple comparisons but does not appear to have applied any correction for multiple testing. This could increase the risk of Type I errors, leading to false-positive results. We recommend that the authors consider using appropriate methods for multiple comparison correction, such as the Bonferroni correction or false discovery rate methods [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In conclusion, while Setoyama et al.'s study provides important insights into the relationship between dynapenic obesity and cardiovascular disease ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873944","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}