Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"The Stimulator of Interferon Genes Deficiency Attenuates Diabetic Myopathy Through Inhibiting NLRP3-Mediated Pyroptosis.","authors":"Jingjuan Yang, Mengqiong Wang, Lingling Shi, Xin Fang, Cui Gao, Lin Ma, Yongfei Wang, Songmin Ying, Yi Yang","doi":"10.1002/jcsm.13649","DOIUrl":"10.1002/jcsm.13649","url":null,"abstract":"<p><strong>Background: </strong>Diabetic myopathy is characterized by the loss of skeletal muscle mass and function. NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis is a type of proinflammatory cell death, which can exacerbate significant muscle cell loss and adverse remodelling. The stimulator of interferon genes (STING) is an essential molecule involved in the regulation of inflammation and immune responses across various diseases. The regulatory mechanism by which STING affects muscle pyroptosis in diabetic myopathy remains unclear.</p><p><strong>Methods: </strong>STING-knockout and wild-type (WT) mice underwent intraperitoneal injection of streptozotocin (STZ). STING small interfering RNA (siRNA) was transfected into fully differentiated C2C12 myotubes prior to glucose treatment. Muscle function tests, body composition analysis, transmission electron microscopy, scanning electron microscopy, western blotting, immunofluorescence, immunohistochemistry, histology, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction were performed. Co-immunoprecipitation assays were employed to investigate the interaction between STING and NLRP3.</p><p><strong>Results: </strong>STING expression was elevated in the gastrocnemius muscle (GM) tissues of WT diabetic mice. STING-deficient diabetic mice exhibited pronounced hyperglycaemia accompanied by hypoinsulinaemia, with no significant difference compared with WT diabetic mice. However, STING-deficient diabetic mice demonstrated a significantly increased body weight and lean mass. A significant decrease in muscle weight, myofibrillar diameter and area, muscle function, and the expression of genes related to muscle atrophy (MuRF1, Atrogin1) were observed in WT diabetic mice, which was mitigated in STING-deficient diabetic mice. STING deficiency reduced the number of GSDMD-N formed pores and pyroptosis-related components (NLRP3, caspase-1, cle-caspase-1, GSDMD, and GSDMD-N) in the GM tissues and was associated with a reduction in inflammatory chemokines. Similar changes were observed in vitro with glucose-induced myotube atrophy and pyroptosis as seen in vivo. Activation of STING by the agonist diABZI exacerbated muscle atrophy and pyroptosis in C2C12 myotubes. Co-localization of STING and NLRP3 was observed, and the interaction between STING and NLRP3 was enhanced in GM tissues from WT diabetic mice. We also found that STING could activate NLRP3 dependent on its channel activity, which can be attenuated by treated with C53 (an inhibitor of STING's ion-channel function).</p><p><strong>Conclusions: </strong>In conclusion, our results indicate that STING-induced activation of the NLRP3 inflammasome leads to pyroptosis, resulting in muscle atrophy and dysfunction. These findings not only elucidate the mechanism of STING-induced pyroptosis but also identify STING as a potential therapeutic target for diabetic myopathy.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":"e13649"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724421","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":"Anabolic Sensitivity in Healthy, Lean, Older Men Is Associated With Higher Expression of Amino Acid Sensors and mTORC1 Activators Compared to Young.","authors":"Oscar Horwath, Marcus Moberg, Nathan Hodson, Sebastian Edman, Mats Johansson, Eva Andersson, Gerrit van Hall, Olav Rooyackers, Andrew Philp, William Apró","doi":"10.1002/jcsm.13613","DOIUrl":"10.1002/jcsm.13613","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is thought to be underlined by age-associated anabolic resistance and dysregulation of intracellular signalling pathways. However, it is unclear whether these phenomena are driven by ageing per se or other confounding factors.</p><p><strong>Methods: </strong>Lean and healthy young (n = 10, 22 ± 3 years, BMI; 23.4 ± 0.8 kg/m²) and old men (n = 10, 70 ± 3 years, BMI; 22.7 ± 1.3 kg/m²) performed unilateral resistance exercise followed by intake of essential amino acids (EAA). Muscle biopsies were collected from the rested and the exercised leg before, immediately after and 60 and 180 min after EAA intake. Muscle samples were analysed for amino acid concentrations, muscle protein synthesis (MPS) and associated anabolic signalling.</p><p><strong>Results: </strong>Following exercise, peak plasma levels of EAA and leucine were similar between groups, but the area under the curve was ~11% and ~28% lower in Young (p < 0.01). Absolute levels of muscle EAA and leucine peaked 60 min after exercise, with ~15 and ~21% higher concentrations in the exercising leg (p < 0.01) but with no difference between groups. MPS increased in both the resting (~0.035%·h^-1 to 0.056%·h^-1, p < 0.05) and exercising leg (~0.035%·h^-1 to 0.083%·h^-1, p < 0.05) with no difference between groups. Phosphorylation of S6K1^Thr389 increased to a similar extent in the exercising leg in both groups but was 2.8-fold higher in the resting leg of Old at the 60 min timepoint (p < 0.001). Phosphorylation of 4E-BP1^Ser65 increased following EAA intake and exercise, but differences between legs were statistically different only at 180 min (p < 0.001). However, phosphorylation of this site was on average 78% greater across all timepoints in Old (p < 0.01). Phosphorylation of eEF2^Thr56 was reduced (~66% and 39%) in the exercising leg at both timepoints after EAA intake and exercise, with no group differences (p < 0.05). However, phosphorylation at this site was reduced by ~27% also in the resting leg at 60 min, an effect that was only seen in Old (p < 0.01). Total levels of Rheb (~45%), LAT1 (~31%) and Rag B (~31%) were higher in Old (p < 0.001).</p><p><strong>Conclusion: </strong>Lean and healthy old men do not manifest AR as evidenced by potent increases in MPS and mTORC1 signalling following EAA intake and exercise. Maintained anabolic sensitivity with age appears to be a function of a compensatory increase in basal levels of proteins involved in anabolic signalling. Therefore, our results suggest that age per se does not appear to cause AR in human skeletal muscle.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":"e13613"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on 'Systematic Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets for Sarcopenia' by Yin Et Al.","authors":"Tianrui Liu, Feixiang Yang, Kun Wang, Peng Guo, Jialin Meng","doi":"10.1002/jcsm.13589","DOIUrl":"10.1002/jcsm.13589","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":"e13589"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666554","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":"Concordance of Freehand 3D Ultrasound Muscle Measurements With Sarcopenia Parameters in a Geriatric Rehabilitation Ward.","authors":"Jeremie Huet, Antoine Nordez, Aurélie Sarcher, Marie Mathieu, Christophe Cornu, Anne-Sophie Boureau","doi":"10.1002/jcsm.13648","DOIUrl":"10.1002/jcsm.13648","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is a devastating disease for older adults, but it lacks accessible and reliable tools for measuring total appendicular skeletal muscle mass (ASMM). Two-dimensional muscle ultrasound (US) has been developed for its bedside clinical advantages and feasibility but lacks standardization and prediction performance. We previously validated a new 3D-US technique to measure muscle volume (MV) at bedside and applied it in a geriatric rehabilitation setting. Objectives were to analyse the concordance between 3D-US MV and ASMM and compare concordance between 3D-US MV and 2D-US parameters with ASMM.</p><p><strong>Methods: </strong>Participants were recruited in a Geriatric rehabilitation ward in Nantes, France, from May to October 2022. Exclusion criteria were as follows: oedema in the lower limbs or recent history of unilateral lower limb damage or stroke. ASMM was measured with bioelectrical impedance analysis; 3D-US and 2D-US acquisitions were performed on three muscles of the right lower limb. Measures of strength (hand grip, knee extension and ankle dorsiflexion) were also recorded. Reliability of 3D-US MV measurements on 10 participants was high (ICC = 0.99). We used Lin's concordance correlation coefficients (CCC) and bias correction factor for agreement between variables and linear regression models for prediction equations.</p><p><strong>Results: </strong>Fifty-eight participants had an interpretable ASMM of whom 17 (29%) had a diagnosis of sarcopenia. Volumes of TA, RF and VL were all significantly concordant with ASMM measured by BIA (all p values < 0.001), with CCCs respectively of 0.72, 0.61 and 0.60. MV were all significantly concordant with isometric strength (p values < 0.001). Concordance and correlation with ASMM were higher with 3D-US than 2D-US measurements regardless of the muscle. Prediction of ASMM reached an adjusted R² of 0.8 with tibialis anterior volume, biometrics and 2D measurements.</p><p><strong>Conclusions: </strong>This study was the first to use 3D-US in a geriatric setting and develop a model to predict ASMM in very old hospitalized patients. MV measurements with 3D-US proved to be reliable and more concordant with appendicular muscle mass and strength than 2D parameters.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":"e13648"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685528","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":"Assessing Association Between Circulating Bilirubin Levels and the Risk of Frailty: An Observational and Mendelian Randomization Study.","authors":"Jun Wu, Jia-Hao Xu, Hao-Qi Zou, Yi-Jiang Ouyang, Shang-Jie Li, Liang Wu, Jie Zhang, Ming-Juan Yin, Dong-Qing Ye, Jin-Dong Ni","doi":"10.1002/jcsm.13642","DOIUrl":"10.1002/jcsm.13642","url":null,"abstract":"<p><strong>Background: </strong>Bilirubin is a by-product of haemoglobin breakdown and has been reported to be a potent antioxidant recently. While elevated levels of bilirubin have been linked to a reduced risk of various diseases, their role remains unknown in frailty. This study aims to explore the relationship between serum bilirubin levels and the risk of frailty.</p><p><strong>Methods: </strong>This cohort study included 442 223 White British participants (aged 39 to 73 years) with an available frailty index at baseline (2006 to 2010) from the UK Biobank. The associations of total/direct bilirubin levels with the continuous frailty index were analysed by multivariable linear regression, and multivariable logistic regression was used after classifying frailty outcomes into non-frailty, pre-frailty and frailty. A Mendelian randomization (MR) analysis was applied to evaluate the association of genetically predicted bilirubin levels with frailty risk.</p><p><strong>Results: </strong>The prevalence rates of both pre-frailty and frailty were 46.17% and 12.49%, respectively, with higher rates observed in women than in men (pre-frailty: 47.33% vs. 44.79%, frailty: 13.64% vs. 11.13%, respectively). There was a non-linear negative association between total bilirubin levels and frailty indexes (p < 0.0001). Mildly elevated total bilirubin levels had protective effects against pre-frailty (OR = 0.863, 95% CI: 0.849 to 0.879, p < 0.001) and frailty (OR = 0.660, 95% CI: 0.641 to 0.679, p < 0.001). Increased total bilirubin levels were more beneficial for women with frailty risk (percent changes per SD μmol/L = -0.37%, 95% CI: -0.40% to -0.34%). The MR analysis revealed a negative association between genetically predicted total/direct bilirubin levels and frailty risk (both p < 0.0001).</p><p><strong>Conclusions: </strong>Circulating total/direct bilirubin levels were negatively associated with frailty risk in White British individuals. Mildly elevated total bilirubin levels were more beneficial for women subpopulation.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":"1-11"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708844","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":"Transcriptomic Profiling Reveals Differences in Slow-Twitch and Fast-Twitch Muscles of a Cigarette Smoke-Exposed Rat Model.","authors":"Timothy K H Fung, Kwok Kuen Cheung, Xia Wang, Benson W M Lau, Shirley P C Ngai","doi":"10.1002/jcsm.13633","DOIUrl":"10.1002/jcsm.13633","url":null,"abstract":"<p><strong>Background: </strong>Cigarette smoking is known to affect muscle function and exercise capacity, including muscle fatigue resistance. Most studies showed diminished cross-sectional area and fibre type shifting in slow-twitch muscles such as the soleus, while effects on fast-twitch muscles were seldom reported and the differential responses between muscle types in response to exposure to cigarette smoke (CS) were largely unknown. This study aimed to elucidate the histomorphological, biochemical and transcriptomic changes induced by CS on both slow-twitch and fast-twitch muscles.</p><p><strong>Method: </strong>Male Sprague-Dawley rats were randomly divided into two groups: sham air (SA) and CS. The rats were exposed to CS for 8 weeks using an exposure chamber system to mimic smoking conditions. Histomorphological analyses on muscle fibre type and cross-sectional area were determined in soleus and extensor digitorum longus (EDL). Transcriptomic profiles were investigated for identifying differentially expressed genes (DEGs) and potential mechanistic pathways involved. Inflammatory responses in terms of the macrophage population and the level of inflammatory cytokines were measured. Markers for muscle-specific proteolysis were also examined.</p><p><strong>Result: </strong>Soleus muscle, but not in EDL, exhibited a significant increase in Type IIa fibres (SA: 9.0 ± 3.3%; CS: 19.8 ± 2.4%, p = 0.002) and decrease in Type I fibres (SA: 90.1 ± 3.6%; CS: 77.9 ± 3.3%, p = 0.003) after CS exposure. RNA sequencing revealed 165 identified DEGs in soleus including upregulation of 'Cd68', 'Ccl2' and 'Ucp2' as well as downregulation of 'Ucp3', etc. Pathways enrichment analysis revealed that the upregulated pathways in soleus were related to immune system and cellular response, while the downregulated pathways were related to oxidative metabolism. Only 10 DEGs were identified in EDL with less enriched pathways. The soleus also showed elevated pro-inflammatory cytokines, and the total macrophage marker CD68 was significantly higher in soleus of CS compared to the SA group (CD68⁺/no. of fibre: SA = 60.3 ± 39.3%; CS = 106.5 ± 27.2%, p = 0.0039), while the two groups in EDL muscle showed no significant difference. The expression of E3 ubiquitin ligase atrogin-1 associated with muscle degradation pathways was 1.63-fold higher in the soleus after CS, while no significant differences were observed in the EDL.</p><p><strong>Conclusion: </strong>The CS-induced inflammatory responses on soleus muscle are likely mediated via targeting mitochondrial-related signalling, resulting in mitochondrial dysfunction and impaired oxidative capacity. The presumably less active mitochondrial-related signalling in EDL renders it less susceptible to changes towards CS, accounting for differential impacts between muscle types.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":"e13633"},"PeriodicalIF":8.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749469","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":"Transcriptomic Profiling Reveals 17β-Estradiol Treatment Represses Ubiquitin-Proteasomal Mediators in Skeletal Muscle of Ovariectomized Mice","authors":"Georgios Kararigas, Mara C. Ebeling, Gengyun Le, Shaojuan Lai, Chunmei Cui, Qinghua Cui, Dawn A. Lowe","doi":"10.1002/jcsm.13698","DOIUrl":"https://doi.org/10.1002/jcsm.13698","url":null,"abstract":"With a decline of 17β-estradiol (E2) at menopause, E2 has been implicated in the accompanied loss of skeletal muscle mass and strength. We aimed at characterizing transcriptomic responses of skeletal muscle to E2 in female mice, testing the hypothesis that genes and pathways related to contraction and maintenance of mass are differentially expressed in ovariectomized mice with and without E2 treatment.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"58 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Descriptive Epidemiology and Prognostic Significance of Diaphragm Thickness in the General Population: The Nagahama Study","authors":"Yasuharu Tabara, Takeshi Matsumoto, Kimihiko Murase, Takahisa Kawaguchi, Kazuya Setoh, Tomoko Wakamura, Toyohiro Hirai, Kazuo Chin, Fumihiko Matsuda","doi":"10.1002/jcsm.13690","DOIUrl":"https://doi.org/10.1002/jcsm.13690","url":null,"abstract":"Diaphragm thickness is a potential marker of sarcopenia in addition to muscle mass and strength at extremities. We aimed to clarify the descriptive epidemiology and prognostic significance of diaphragm thickness in the general population.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"34 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Cachexia and Outcomes in Patients With Chronic Diseases: A National Database Analysis of 5 484 103 Hospitalisations","authors":"Mitja Lainscak, Tina Zupanic, Daniel Omersa, Ivan Erzen, Jerneja Farkas","doi":"10.1002/jcsm.13688","DOIUrl":"https://doi.org/10.1002/jcsm.13688","url":null,"abstract":"Cachexia is a frequent companion of chronic diseases and a well-established predictor of poor patient performance and outcome. Since cachexia as a discharge diagnosis is not much investigated, we aimed to investigate prevalence of cachexia in hospitalised patients and their outcome.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"28 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle Loss During First‐Line Chemotherapy Impairs Survival in Advanced Pancreatic Cancer Despite Adapted Physical Activity","authors":"Pauline Parent, Frédéric Pigneur, Marc Hilmi, Aurélien Carnot, Marie‐Line Garcia Larnicol, Dewi Vernerey, Alain Luciani, Pascal Hammel, Julie Henriques, Cindy Neuzillet, Anthony Turpin","doi":"10.1002/jcsm.13595","DOIUrl":"https://doi.org/10.1002/jcsm.13595","url":null,"abstract":"BackgroundAdvanced pancreatic ductal adenocarcinoma (aPDAC) is often accompanied by significant muscle mass loss, contributing to poor prognosis. SarcAPACaP, an ancillary study of the GERCOR‐APACaP phase III trial, evaluated the role of adapted physical activity (APA) in aPDAC Western patients receiving first‐line chemotherapy. The study aimed to assess (1) the potential impact of computed tomography (CT)–quantified muscle mass before and during treatments on health‐related quality of life (HRQoL) and overall survival (OS) and (2) the role of APA in mitigating muscle mass loss.MethodsIn the APACaP trial, aPDAC patients with ECOG performance status (PS) 0–2 were randomized 1:1 to usual care including first‐line chemotherapy or usual care plus a 16‐week home‐based APA program. In the SarcAPACaP study, the surface muscular index (SMI) was determined from L3 CT scan slices. Two patient populations were analysed: those with CT scan available at baseline (modified[m] intent‐to‐treat [ITT]1‐W0) and those with CT scans available at both W0 and W16 (mITT2 W0–W16). Low muscle mass was defined by low SMI with SMI &lt; 41 cm<jats:sup>2</jats:sup>/m<jats:sup>2</jats:sup> for women and &lt; 43 and &lt; 53 cm<jats:sup>2</jats:sup>/m<jats:sup>2</jats:sup> for men with body max index &lt; 25.0 and ≥ 25.0 kg/m<jats:sup>2</jats:sup>, respectively. Muscle loss was defined by the relative difference of SMI between W0 and W16 (100*[SMI W16–SMI W0]/SMI W0). In mITT2 W0–W16, patients were stratified into three groups based on the severity of muscle loss: none, moderate (0%–10%) and high (≥ 10%). Associations between muscle mass loss and OS, time until definitive deterioration (TUDD) of HRQoL and the effect of APA on loss of muscle mass were assessed.ResultsBetween October 2014 and May 2020, 313 patients were prospectively enrolled, with 225 in mITT1 W0 and 128 in mITT2 W0–W16, with 65 assigned to the APA arm. Both groups had similar baseline characteristics with comparable OS and TUDD. A low SMI at W0 was not associated with OS and TUDD of HRQoL in either group. Among mITT2 W0–W16 patients, high muscle mass loss (<jats:italic>n</jats:italic> = 27) independently predicted OS (<jats:italic>p</jats:italic> = 0.012) and showed a trend toward negatively affecting TUDD of HRQoL. Notably, APA did not mitigate muscle loss in our study population.ConclusionsLongitudinal muscle mass loss emerged as a predictive factor for both OS and HRQoL in aPDAC patients undergoing chemotherapy, while a low SMI at diagnosis did not provide prognostic value. APA did not impact muscle mass loss in this population.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"7 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}