Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Transcriptional Co-Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone-Induced Muscle Atrophy via mTOR Signalling","authors":"Kyung Min Kim,&nbsp;Ho Taek Oh,&nbsp;Youjin Do,&nbsp;Gi Don Yoo,&nbsp;Woong Heo,&nbsp;Jeekeon Park,&nbsp;Hyejin Yang,&nbsp;Suh Jin Yoon,&nbsp;Mi Ran Byun,&nbsp;Eun Sook Hwang,&nbsp;Jeong-Ho Hong","doi":"10.1002/jcsm.13790","DOIUrl":"10.1002/jcsm.13790","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glucocorticoid therapy has a beneficial effect in several diseases, but chronic treatment has adverse effects, including muscle atrophy, which refers to the gradual decrease in muscle mass, size and strength. It is important to know how the muscle atrophy occurs, but the underlying mechanism is not yet fully understood. This study shows that dexamethasone decreases levels of the transcriptional co-activator with PDZ binding motif (TAZ), which facilitates dexamethasone-induced muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To induce muscle atrophy, C2C12 myotubes were treated with dexamethasone, and mice were fed with water containing dexamethasone. Muscle atrophy was analysed for the expression of myosin heavy chain, MuRF1 and Atrogin-1 using immunofluorescence staining, immunoblot analysis and qRT-PCR. Muscle tissue was analysed by haematoxylin and eosin staining. Adeno-associated virus was used for overexpression of wild-type and mutant TAZ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TAZ levels decrease in dexamethasone-treated mice (0.36-fold, <i>p</i> &lt; 0.001) and C2C12 myotubes (0.44-fold, <i>p</i> = 0.024). Overexpression of the TAZ mutant, which resists its proteolytic degradation, inhibits dexamethasone-induced muscle atrophy. Atrogin-1 and MuRF1 interact with TAZ and facilitate its degradation in dexamethasone-treated C2C12 myotubes. TAZ mutant stimulates protein synthesis through activation of mTOR signalling via induction of RhebL1 (DEX; Con vs, TAZ4SA: 5.1-fold, <i>p</i> &lt; 0.001) in dexamethasone-treated mice. Ginsenoside Rb3 increases TAZ levels in dexamethasone-treated mice (1.49-fold, <i>p</i> = 0.007) and C2C12 myotubes (1.63-fold, <i>p</i> = 0.01), which stimulates mTOR signalling and inhibits dexamethasone-induced muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results demonstrate a novel regulatory mechanism of dexamethasone-induced muscle atrophy by TAZ, suggesting that stabilisation of TAZ in muscle cells ameliorates the muscle atrophy. These results suggest that TAZ may be a drug target for the dexamethasone-induced muscle atrophy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body Composition Assessment Provides Prognostic Information in Patients With Cancer Affected by Chronic Graft vs. Host Disease","authors":"Asmita Mishra,&nbsp;Ram Thapa,&nbsp;Kevin Bigam,&nbsp;Martine Extermann,&nbsp;Rawan Faramand,&nbsp;Farhad Khimani,&nbsp;Xuefeng Wang,&nbsp;Vickie Baracos,&nbsp;Joseph A. Pidala","doi":"10.1002/jcsm.13759","DOIUrl":"https://doi.org/10.1002/jcsm.13759","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;Additional tools are needed to assess mortality risk among patients with cancer. Patients with chronic graft vs. host disease (cGVHD) after allogeneic haematopoietic cell transplantation (HCT) represent a high-risk cancer population with mortality risk explained by cGVHD severity, but also informed by baseline comorbidities, functional status before and after HCT, and cumulative toxicity from the procedure and its complications. Radiographic body composition metrics from CT scans have previously shown association with complications in other populations.&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 examined a single-centre consecutive series (2005–2016) of HCT recipients with cGVHD and CT-scans immediately proximal to cGVHD diagnosis to investigate association of radiographic body composition measures and mortality. Skeletal muscle index (SMI) and fat index (FI) were quantified on CT imaging at the 3rd lumbar (L3) and 4th thoracic (T4) vertebra. SM Hounsfield units (HU) were obtained to evaluate SM density. Cut points for SMI were from literature and cut points for FI were established by sex-specific optimal stratification.&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 &lt;i&gt;n&lt;/i&gt; = 113 patients met the inclusion criteria for this analysis, aged 51.2 ± 10.5(SD) years and predominantly male (&lt;i&gt;n&lt;/i&gt; = 71, 63%) and diagnosed with NHL (&lt;i&gt;n&lt;/i&gt; = 110, 97%). Onset cGVHD NIH overall severity was mild in &lt;i&gt;N&lt;/i&gt; = 56 (49%), moderate in 44 (38%) and severe in 15 (13%), with median time to cGVHD onset after HCT of 173 days [IQR 122;295]. A CT scan at 77 days [IQR 33;202] post HCT was selected for analysis. In multivariate analysis, CT-defined body fat ≥ 35% was independently associated with increased mortality (HR 2.094 (95% CI 1.060, 4.136), &lt;i&gt;p&lt;/i&gt; = 0.033) overall. Patients of male sex had higher FI than females and showed a more prominent association between high FI and mortality. SMI as well as other indices of adiposity were not associated with survival in multivariable analysis including BMI, sarcopenic obesity and low skeletal muscle radiodensity. In exploratory analyses, we demonstrated similar results per CT chest at T4, suggesting possible future application to a larger HCT population.&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 data support that radiographic body composition measures provide prognostic information among patients with cancer affected by cGVHD post-HCT and suggest that high body fat % is a promising candidate for future study. These findings suggest that low skelet","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717182","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 “The Prevalence Patterns and Risk Factor Profiles of Poor Muscle Health and Its Associated Components in Multi-Ethnic Older Asians: The PIONEER Study”","authors":"","doi":"10.1002/jcsm.13774","DOIUrl":"https://doi.org/10.1002/jcsm.13774","url":null,"abstract":"<p>\u0000 <span>Gupta, P</span>, <span>Vu, TA</span>, <span>Man, REK</span>, et al., <span>The prevalence patterns and risk factor profiles of poor muscle health and its associated components in multiethnic older Asians: The PIONEER study</span>. <i>Journal of cachexia, sarcopenia and muscle</i>. Aug <span>2024</span>; <span>15</span>(<span>4</span>): <span>1376</span>–<span>1387</span>. doi:10.1002/jcsm.13483\u0000 </p><p>In the Funding ‘section’, we would like to add: “This research is supported by the National Medical Research Council (NMRC) through the SingHealth PULSES II Centre Grant (CG21APR1013).” After this sentence, it continues to read: “The grant body had no roles in design, conduct or data analysis of the study, nor in manuscript preparation and approval.”</p><p>We apologize for this error.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13774","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717326","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":"A Novel Definition and Grading Diagnostic Criteria for Tumour-Type-Specific Comprehensive Cachexia Risk","authors":"Chunlei Hu,&nbsp;Minghua Cong,&nbsp;Chunhua Song,&nbsp;Hongxia Xu,&nbsp;Zengqing Guo,&nbsp;Fuxiang Zhou,&nbsp;Lan Zhou,&nbsp;Min Weng,&nbsp;Benqiang Rao,&nbsp;Li Deng,&nbsp;Kaiying Yu,&nbsp;Yongbing Chen,&nbsp;Ziwen Wang,&nbsp;Guotian Ruan,&nbsp;Ming Yang,&nbsp;Chenan Liu,&nbsp;Jiuwei Cui,&nbsp;Wei Li,&nbsp;Kunhua Wang,&nbsp;Zengning Li,&nbsp;Ming Liu,&nbsp;Tao Li,&nbsp;Junqiang Chen,&nbsp;Stephan von Haehling,&nbsp;Rocco Barazzoni,&nbsp;Hanping Shi","doi":"10.1002/jcsm.13744","DOIUrl":"10.1002/jcsm.13744","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;The existing diagnostic criteria for cancer cachexia do not meet clinical needs. We aimed to establish novel comprehensive evaluation scales for cachexia specific to patients with solid tumours.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study included 12 651 patients (males: 6793 [53.7%]; females: 5858 [46.3%]; medium age: 58 [interquartile range:50/66] years; medium follow-up duration: 24.16 [13.32/44.84] months; 4271 [33.8%] patients died; mean survival: 55.53 [95% confidence interval, 54.87/56.10] months; 3344 [26.4%], 4184 [33.1%] and 5123 [40.5%] patients with Stage I–II, III and IV tumour, respectively; derivation set: 10022, validation set: 2629 patients) with 14 types of solid tumours, including lung, gastric, liver, breast, oesophageal, cervical, bladder, pancreatic, prostate, ovarian, colorectal cancer, nasopharyngeal and endometrial carcinoma and cholangiocarcinoma, from an open and ongoing multicentre cohort study in China. Risk factors for cachexia, including tumour characteristics and nutritional parameters, were examined to develop diagnostic scales using Cox proportional hazards models and Kaplan–Meier analysis.&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;Ten nutrition items (body mass index, weight loss, intake reduction, physical activity function, fatigue, handgrip strength, anorexia, albumin level, albumin/globulin ratio and neutrophil/lymphocyte ratio) with different weighted scores were identified to construct a nutrition-weighted scoring scale (NWSS) for nutrition risk. Tumour type and tumour burden status (tumour-node-metastasis stage and radical or non-radical tumour) were determined to construct a disease-weighted scoring scale (DWSS) for disease risk. A lumped scale (5 × 5 matrix) established using a five-grade classification of nutrition and disease risk was used to determine a five-grade classification of comprehensive cachexia risk: A, no cachexia risk (reference; lowest disease and nutrition risks); B, cachexia risk (hazard ratio [HR] = 4.517 [4.033/5.058]); C, pre-cachexia (HR = 9.755 [8.73/10.901], medium survival = 21.21 months); D, cachexia (HR = 16.901 [14.995/19.049], medium survival = 11.61 months); and E, refractory cachexia (HR = 31.879 [28.244/35.981], medium survival = 4.83 months, highest disease and nutrition risks) (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Patients in Categories A–D benefited from nutrition therapy and anti-tumour treatments to varying degrees. Patients in Category E were clinically refractory to nutrition therapy without prolonged survival compared with patients without nutrition therapy (medium survival, pre-hospitalization nutrition therapy vs. hospital","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666334","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":"snRNA-Seq and Spatial Transcriptome Reveal Cell–Cell Crosstalk Mediated Metabolic Regulation in Porcine Skeletal Muscle","authors":"Liu Guo,&nbsp;Mengmeng Han,&nbsp;Junfei Xu,&nbsp;Wenyue Zhou,&nbsp;Hanjing Shi,&nbsp;Sisi Chen,&nbsp;Weijun Pang,&nbsp;Xing Zhang,&nbsp;Yehui Duan,&nbsp;Yulong Yin,&nbsp;Fengna Li","doi":"10.1002/jcsm.13752","DOIUrl":"https://doi.org/10.1002/jcsm.13752","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;Cell–cell crosstalk between myogenic, adipogenic and immune cells in skeletal muscle to regulate energy metabolism and lipid deposition has received considerable attention. The specific mechanisms of interaction between the different cells in skeletal muscle are still 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;Using integrated analysis of snRNA-seq and spatial transcriptome, the gene expression profile of &lt;i&gt;longissimus dorsi&lt;/i&gt; (LD) muscle was compared between adult Taoyuan black (TB, obese, native Chinese breed) and Duroc (lean) pigs.&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;TB pig had more intramuscular fat (IMF) deposition (3.91%, &lt;i&gt;p&lt;/i&gt; = 0.0244) and higher slow myofiber proportion (17.13%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) compared with Duroc pig (IMF, 2.38%; slow myofiber, 6.92%) at the age of 180 days. We identified eight cell populations in porcine LD muscle. Five subpopulations of myonuclei and 10 subclusters of fibro/adipogenic progenitors (FAPs) were defined by marker genes. CellChat analysis revealed that communication between immune cells and other cells via the BMP and EGF signalling pathway was only observed in Duroc and not in TB pig. Both snRNA-seq and spatial transcriptome pointed out that FAPs are the important source of secretory proteins. A total of 35 upregulated and 23 downregulated differentially expressed genes (DEGs) were annotated as secretory, one upregulated and 36 downregulated secretory DEGs were identified between TB and Duroc pigs in FAPs by snRNA-seq and FAPs-high regions by spatial transcriptome, respectively. The distribution of FAPs was accompanied by the divergent myofiber-type composition. The expression level of slow myofiber marker gene (&lt;i&gt;MYH7&lt;/i&gt;) was higher in both FAPs-high and FAPs-low regions of TB compared with Duroc pig (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001), and expression level of fast myofiber maker gene (&lt;i&gt;MYH1&lt;/i&gt;) was upregulated in FAPs-high region of Duroc compared with FAPs-high region of TB (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and FAPs-low region of Duroc pig (&lt;i&gt;p&lt;/i&gt; = 0.0002). The metabolic differences of myofibers between TB and Duroc pigs were mainly concentrated in energy, lipid and nitrogen metabolism-related pathway (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). The significant correlation (&lt;i&gt;R&lt;/i&gt; &gt; 0.4, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) between secretory and metabolism-related DEGs with spatial aggregation was verified by regression analysis for random region extraction (area of 25 spots, &lt;i&gt;n&lt;/i&gt; = 400) from spatial transcriptome, and we speculated that the alteration of secretory proteins forming the microenvironment might regulate myofiber metabolism via target genes such as &lt;i&gt;IRS1&lt;/i&gt;, &lt;i&gt;","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13752","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602568","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":"Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series","authors":"Olav Dajani,&nbsp;Iain Philips,&nbsp;Ester Kristine Størkson,&nbsp;Trude R. Balstad,&nbsp;Leo R. Brown,&nbsp;Asta Bye,&nbsp;Ross Dolan,&nbsp;Christine Greil,&nbsp;Marianne Hjermstad,&nbsp;Gunnhild Jakobsen,&nbsp;Stein Kaasa,&nbsp;James McDonald,&nbsp;Inger Ottestad,&nbsp;Judith Sayers,&nbsp;Melanie Simpson,&nbsp;Mariana S. Sousa,&nbsp;Ola Magne Vagnildhaug,&nbsp;Michael S. Yule,&nbsp;Barry J. A. Laird,&nbsp;Richard J. E. Skipworth,&nbsp;Tora S. Solheim,&nbsp;Mark Stares,&nbsp;Jann Arends,&nbsp;the Cancer Cachexia Endpoints Working Group","doi":"10.1002/jcsm.13756","DOIUrl":"https://doi.org/10.1002/jcsm.13756","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 patients receiving anti-cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials.&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;An electronic literature search of MEDLINE, Embase and Cochrane databases (1990–2023) was performed. Eligibility criteria comprised participants ≥ 18 years old; controlled design; ≥ 40 participants; and a cachexia intervention for &gt; 14 days. Trials reporting at least one oncological endpoint were selected for analysis. Data extraction was performed using Covidence and followed PRISMA guidelines and the review was registered (PROSPERO CRD42022276710).&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;Fifty-seven trials were eligible, totalling 9743 patients (median: 107, IQR: 173). Twenty-six (46%) trials focussed on a single tumour site: eight in lung, six in pancreatic, six in head and neck and six in GI cancers. Forty-two (74%) studies included patients with Stage III/IV disease, and 41 (70%) included patients receiving palliative anti-cancer treatment. Ten studies (18%) involved patients on curative treatment. Twenty-eight (49%) studies used pharmacological interventions, 29 (50%) used oral nutrition, and two (4%) used enteral or parenteral nutrition. Reported oncological endpoints included overall survival (OS, &lt;i&gt;n&lt;/i&gt; = 46 trials), progression-free survival (PFS, &lt;i&gt;n&lt;/i&gt; = 7), duration of response (DR, &lt;i&gt;n&lt;/i&gt; = 1), response rate (RR, &lt;i&gt;n&lt;/i&gt; = 9), completion of treatment (TC, &lt;i&gt;n&lt;/i&gt; = 11) and toxicity/adverse events (AE, &lt;i&gt;n&lt;/i&gt; = 42). Median OS differed widely from 60 to 3468 days. Of the 46 studies, only three reported a significant positive effect on survival. Seven trials showed a difference in AE, four in TC, one in PFS and one in RR. Reported significances were unreliable due to missing adjustments for extensive multiple testing. Only three of the six trials using OS as the primary endpoint reported pre-trial sample size calculations, but only one recruited the planned number of patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In CC trials, oncological endpoints were mostly secondary and only few significant findings have been reported. Due to heterogeneity in oncological settings, nutritional and metabolic status and interventions, firm conclusions about CC treatment are not possible. OS and AE are relevant endpoints, but future trials targeting clinically me","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595147","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":"Therapeutic Targeting of Decr1 Ameliorates Cardiomyopathy by Suppressing Mitochondrial Fatty Acid Oxidation in Diabetic Mice","authors":"Qing-Bo Lu,&nbsp;He-Ting Sun,&nbsp;Kuo Zhou,&nbsp;Jia-Bao Su,&nbsp;Xin-Yu Meng,&nbsp;Guo Chen,&nbsp;Ao-Yuan Zhang,&nbsp;An-Jing Xu,&nbsp;Chen-Yang Zhao,&nbsp;Yuan Zhang,&nbsp;Yao Wang,&nbsp;Hong-Bo Qiu,&nbsp;Zhuo-Lin Lv,&nbsp;Zheng-Yang Bao,&nbsp;Jian Zhu,&nbsp;Feng Xiao,&nbsp;Xue-Xue Zhu,&nbsp;Hai-Jian Sun","doi":"10.1002/jcsm.13761","DOIUrl":"https://doi.org/10.1002/jcsm.13761","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;A significant increase in mitochondrial fatty acid oxidation (FAO) is now increasingly recognized as one of the metabolic alterations in diabetic cardiomyopathy (DCM). However, the molecular mechanisms underlying mitochondrial FAO impairment in DCM remain to be fully elucidated.&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 type 2 diabetes (T2D) mouse model was established by a combination of high-fat diet (HFD) and streptozotocin (STZ) injection. Neonatal rat cardiomyocytes were treated with high glucose (HG) and palmitic acid (HP) to simulate diabetic cardiac injury. Gain- and loss-of-function approaches and RNA sequencing were utilized to investigate the role and mechanism of 2,4-dienoyl-CoA reductase 1 (Decr1) in DCM.&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;By integrating the genomic data available in the Gene Expression Omnibus (GEO) with DCM rodents, we found that the transcriptional level of Decr1 was consistently upregulated in DCM (+255% for diabetic heart, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; +281% for diabetic cells, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Cardiomyocytes-specific knockdown of Decr1 preserved cardiac function (+41% for EF, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; +24% for FS, &lt;i&gt;p&lt;/i&gt; = 0.0052), inhibited cardiac hypertrophy (−34%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), fibrosis (−69%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), apoptosis (−56%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and oxidative damage (−59%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) in DCM mice, while cardiomyocytes-specific overexpression of Decr1 aggravated DCM (−28% for EF, &lt;i&gt;p&lt;/i&gt; = 0.0347; −17% for FS, &lt;i&gt;p&lt;/i&gt; = 0.0014). Deletion of Decr1 prevented high glucose/palmitate (HG/HP)-induced hypertrophy (−22%, &lt;i&gt;p&lt;/i&gt; = 0.0006), mitochondrial dysfunction and apoptosis (−74%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) in cultured cardiomyocytes. Furthermore, RNA sequencing and functional analysis showed that Decr1 interacted with and upregulated pyruvate dehydrogenase kinase 4 (PDK4) in injured cardiomyocytes, and overexpression of PDK4 eliminated the benefits of Decr1 downregulation in DCM (−20% for EF, &lt;i&gt;p&lt;/i&gt; = 0.0071; −28% for FS, &lt;i&gt;p&lt;/i&gt; = 0.0022). Mechanistically, PDK4 acted as a kinase that induced phosphorylation and mitochondrial translocation of HDAC3. In the mitochondria, HDAC3 mediated the deacetylation of dehydrogenase trifunctional multienzyme complex α subunit (HADHA), contributing to excessive mitochondrial FAO and subsequent cardiac injury. From a screening of 256 natural products, we identified Atranorin and Kurarinone as potential inhibitors of Decr1, both demonstrating protective effects against DCM (Atranorin, +21% for EF, &lt;i&gt;p&lt;/i&gt; = 0.0134; +24% for FS, &lt;i&gt;p&lt;/i&gt; = 0.0006; Kurarinone, +20% for EF, &lt;i&gt;p&lt;/i&gt; = 0.0183; +27% fo","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564757","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":"Paradoxical Effect of Myosteatosis on the Immune Checkpoint Inhibitor Response in Metastatic Renal Cell Carcinoma","authors":"Jiwoong Yu,&nbsp;Hyeonju Ahn,&nbsp;Kyung Yeon Han,&nbsp;Wan Song,&nbsp;Hyun Hwan Sung,&nbsp;Hwang Gyun Jeon,&nbsp;Byong Chang Jeong,&nbsp;Seong Il Seo,&nbsp;Seong Soo Jeon,&nbsp;Se Hoon Park,&nbsp;Woong-Yang Park,&nbsp;Ji Hyun Lee,&nbsp;Minyong Kang","doi":"10.1002/jcsm.13758","DOIUrl":"https://doi.org/10.1002/jcsm.13758","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;Treatment for metastatic renal cell carcinoma (mRCC) has shifted from tyrosine kinase inhibitor (TKI) therapy to immune checkpoint inhibitor (ICI)–based therapy, improving outcomes but with variable individual responses. This study investigated the prognostic implications of pretreatment low skeletal muscle mass (LSMM) and myosteatosis in patients with mRCC undergoing first-line ICI-based therapies, comparing outcomes between PD-1 inhibitor + CTLA-4 inhibitor and PD-1 inhibitor + TKI, incorporating single-cell RNA sequencing.&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 retrospective analysis was performed on 90 patients with mRCC treated with ICI-based therapies between November 2019 and March 2023. Patients were grouped based on whether they received PD-1 inhibitor + CTLA-4 inhibitor or PD-1 inhibitor + TKI combinations. LSMM was defined as skeletal muscle index below 40.8 cm&lt;sup&gt;2&lt;/sup&gt;/m&lt;sup&gt;2&lt;/sup&gt; for men and 34.9 cm&lt;sup&gt;2&lt;/sup&gt;/m&lt;sup&gt;2&lt;/sup&gt; for women. Myosteatosis was defined using skeletal muscle density, with cut-off values &lt; 41 HU for BMI &lt; 25 kg/m&lt;sup&gt;2&lt;/sup&gt; and &lt; 33 HU for BMI ≥ 25 kg/m&lt;sup&gt;2&lt;/sup&gt;. Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan–Meier curves and multivariable models. Single-cell RNA sequencing was performed on pretreatment samples to compare the immune microenvironment between patients with and without myosteatosis.&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 cohort (26.7% female; median age: 60.5 years) included 59 patients (65.6%) treated with PD-1 inhibitor + CTLA-4 inhibitor and 31 patients (34.4%) treated with PD-1 inhibitor + TKI. LSMM was present in 18.9% of patients, and myosteatosis in 41.1%, with comparable proportions across groups. During follow-up, 29 patients (32.2%) died: 16 in the PD-1 inhibitor + CTLA-4 inhibitor group and 13 in the PD-1 inhibitor + TKI group. The overall 1-year mortality rate was 22.2%, and PFS rate was 53.3%. Myosteatosis predicted poor OS (HR, 5.389; &lt;i&gt;p&lt;/i&gt; = 0.008) and PFS (HR, 2.930; &lt;i&gt;p&lt;/i&gt; = 0.022) in the PD-1 inhibitor + TKI group but was protective for PFS (HR, 0.461; &lt;i&gt;p&lt;/i&gt; = 0.049) in the PD-1 inhibitor + CTLA-4 inhibitor group. LSMM did not significantly affect outcomes in either group. Single-cell RNA sequencing revealed higher CTLA-4 expression in regulatory T cells and more effector memory CD8&lt;sup&gt;+&lt;/sup&gt; T cells in patients with myosteatosis, whereas patients without myosteatosis had more anti-tumoural non-classical monocytes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564756","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":"Weight Loss in Cancer and the 2017 Common Terminology Criteria for Adverse Events—Dangerous and Misleading","authors":"Aynur Aktas,&nbsp;Kunal C. Kadakia,&nbsp;Jake Waldman,&nbsp;Declan Walsh","doi":"10.1002/jcsm.13754","DOIUrl":"https://doi.org/10.1002/jcsm.13754","url":null,"abstract":"<p>Accurate toxicity reporting in cancer clinical trials is necessary to promote regulatory decision making. Up to 85% of those with some cancers (e.g., oesophagus, head and neck, and pancreas) experience significant progressive weight loss (WL) throughout treatment. Therefore, it is necessary that investigators accurately grade and report WL. We have identified two dangerous and misleading approaches in the CTCAE specific to WL: (1) severity grades and associated clinical descriptions and (2) lack of pretreatment weight and longitudinal weight changes. This review highlights the critical importance of a more accurate, comprehensive and patient-focused WL assessment in oncology clinical trials and the CTCAE. We offer a path forward for identification and management of this life-threatening phenomenon, whether it is due to cancer or an antitumor treatment. The National Cancer Institute should consider the following five ideas and concrete action items for future CTCAE versions: (1) Weight assessment has important implications for toxicity determination and prognosis in clinical trials and should be consistently integrated into study reports; (2) Adverse event assessment should be patient-focused and supported by clinically relevant definitions of each grade level; (3) the CTCAE grades and associated clinical descriptions for WL should be revised to better reflect the impact of WL on trial endpoints and patient safety; (4) WL should be assessed as a continuous variable to capture duration, severity, and trajectory; and (5) WL should be urgently incorporated into the PRO-CTCAE to define the individual impact.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13754","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565204","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. —The Authors' Reply","authors":"Yu Setoyama,&nbsp;Takanori Honda,&nbsp;Toshiharu Ninomiya","doi":"10.1002/jcsm.13764","DOIUrl":"10.1002/jcsm.13764","url":null,"abstract":"<p>We would like to thank Drs. Wang and Huang for their helpful letter [<span>1</span>] regarding our paper [<span>2</span>].</p><p>As they pointed out, the generalizability of our findings is limited because this study was conducted in one town in Japan. Therefore, it would be desirable to verify the relationship between dynapenic obesity and cardiovascular disease (CVD) risk in various countries and regions with diverse backgrounds.</p><p>They also proposed additional subgroup analyses. We compared cardiovascular risk between dynapenic obesity and non-dynapenic obesity by each covariate. As a result, the magnitude of the association of dynapenic obesity with the risk of CVD was stronger among participants with a smoking habit than in those without a smoking habit (<i>p</i> for heterogeneity = 0.04). Smoking has been reported to synergistically increase the risk of developing CVD when combined with hypercholesterolemia [<span>3</span>] and obesity [<span>4</span>]. In our study, the participants with dynapenic obesity had a higher frequency of hypercholesterolemia at baseline. These findings suggest that smoking may require more attention in individuals with dynapenic obesity, especially in middle-aged individuals at high risk for CVD. In addition, we could not compare the risk in the subgroup with regular exercise habits because no CVD events were observed in the participants with dynapenic obesity and regular exercise habits. While this may have been due to chance given the small number of participants with dynapenic obesity who exercised regularly (<i>n</i> = 7), exercise has been shown to improve obesity and its complications [<span>5, 6</span>]. It may also prevent a worse prognosis in people with dynapenic obesity.</p><p>As also pointed out, we could not account for the changes in lifestyle factors such as diet, exercise, smoking and alcohol consumption during the follow-up period in this study. It is certainly possible that cardiovascular risk decreased in participants with dynapenic obesity due to improvements in their lifestyle during the follow-up period, whereas the opposite may have occurred in participants without dynapenic obesity. Consequently, the cardiovascular risk for those with dynapenic obesity at baseline against those without it may have been underestimated in this study. The impact of lifestyle changes on the association between dynapenic obesity and CVD needs to be verified in future studies.</p><p>Finally, we would like to thank Drs. Wang and Huang again for their valuable suggestions on our study. We hope that our study will contribute to promoting health during middle and old age.</p><p>The authors certify that they comply with the ethical guidelines for authorship and publishing in the <i>Journal of Cachexia, Sarcopenia and Muscle</i> [<span>7</span>].</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545889","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}