Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"CXCL14 Promotes Skeletal Muscle Mass Growth and Attenuates Lipopolysaccharide‐ and Dexamethasone‐Induced Muscle Atrophy in Cultured Myotubes and Mouse Models","authors":"Bagus Sarmito, Younjeong Oh, Nurkyz Alymkulova, Jeong Kyo Yoon","doi":"10.1002/jcsm.70087","DOIUrl":"https://doi.org/10.1002/jcsm.70087","url":null,"abstract":"BackgroundSkeletal muscle mass is regulated by secretory factors derived from myofibers and muscle‐resident cells. Identifying these factors and understanding their mechanisms is critical for combating muscle wasting disorders. This experimental study investigates the role of CXCL14, a chemokine primarily secreted by fibro‐adipogenic progenitors (FAPs) residing in muscle, in regulating muscle mass.MethodsThis study was conducted at the Soonchunhyang Institute of Medi‐bio Science (SIMS), South Korea, between August 2020 and June 2025. Mouse C2C12 myotubes and primary human myotubes were treated with recombinant CXCL14, with or without co‐treatment using <jats:italic>Rps6kb1</jats:italic> siRNA, lipopolysaccharide (LPS) or dexamethasone (DEX). Myotube mass index (MMI) was measured. Expression of AKT‐S6 kinase (S6K), FOXO‐Atrogin‐1/MuRF‐1 signalling components and myosin heavy chains (MyHCs) was assessed via Western blotting. Eight‐week‐old male mice were used: ICR mice for electroporation experiments and C57BL/6N strain for LPS and DEX atrophy models. <jats:italic>Cxcl14</jats:italic> expression plasmids were electroporated into tibialis anterior (TA) muscles, with or without LPS or DEX treatment. Cross‐sectional area (CSA) of myofibers was measured; Western blotting and RNA sequencing were used to analyse molecular responses. Statistical analyses included one‐way ANOVA with Tukey's post hoc test, repeated‐measures ANOVA with Dunnett's post hoc test, Kruskal–Wallis test with Dunn's post hoc test and unpaired Student's <jats:italic>t</jats:italic>‐test, as appropriate.ResultsCXCL14 induced hypertrophy in C2C12‐derived myotubes: (MMI [μm<jats:sup>2</jats:sup>]: 100 ng/mL CXCL14, 1345 ± 50.97 [95% CI: 1237–1453], vs. control, 897.9 ± 33.33 [95% CI: 829.8–996], <jats:italic>p ≤</jats:italic> 0.0001). <jats:italic>Cxcl14</jats:italic> overexpression in mouse TA muscles significantly increased muscle mass: (CSA [μm<jats:sup>2</jats:sup>]: HA‐CXCL14: 1408 ± 15.42 [95% CI: 1378–1438]; CXCL14‐Myc: 1499 ± 17.18 [95% CI: 1464–1534]; control: 870.1 ± 11.25 [95% CI: 848.1–892.2], <jats:italic>p ≤</jats:italic> 0.0001). CXCL14 activated the AKT‐S6K pathway and inhibited the FOXO‐Atrogin‐1/MuRF‐1 pathway in both in vitro and in vivo models. CXCL14 effectively reversed LPS‐ and DEX‐induced atrophy in both C2C12 myotubes and TA muscles, as demonstrated by corresponding increases MMI and CSA (all <jats:italic>p</jats:italic> ≤ 0.0001). CXCL14 also promoted hypertrophy in primary human myotubes in vitro (MMI [μm<jats:sup>2</jats:sup>]: 100 ng/mL CXCL14, 3481 ± 242.6 [95% CI: 2973–3989] vs. control, 2549 ± 114.7 [95% CI: 2310–2787], <jats:italic>p</jats:italic> ≤ 0.001) and significantly reversed atrophy induced by LPS and DEX (<jats:italic>p</jats:italic> ≤ 0.01 to <jats:italic>p</jats:italic> ≤ 0.0001), accompanying the activation of protein synthesis and inhibition of protein degradation pathways.ConclusionsOur findings identify CXCL14 as a novel regulator of skele","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"37 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282736","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":"Association Between Sarcopenia and the Long‐Term Risk of Intervertebral Disc Degeneration","authors":"Jianan Chen, Tongzhou Liang, Wenjun Hu, Nianchun Liao, Zaoqiang Zhang, Huihong Shi, Song Liu, Junquan Liang, Yanbo Chen, Youxi Lin, Xianjian Qiu, Dongsheng Huang, Anjing Liang, Wenjie Gao","doi":"10.1002/jcsm.70086","DOIUrl":"https://doi.org/10.1002/jcsm.70086","url":null,"abstract":"BackgroundSarcopenia and intervertebral disc degeneration (IDD) are both highly prevalent among the elderly and have a substantial impact on their quality of life. However, the association between sarcopenia and IDD remains unclear. This study aimed to investigate whether sarcopenia is independently associated with an increased risk of IDD in middle‐aged and older adults, using prospective data from the UK Biobank.MethodsA total of 378 773 participants from the UK Biobank were included and categorized into three groups based on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria: normal, probable sarcopenia and confirmed sarcopenia. The association between sarcopenia and IDD was examined using Kaplan–Meier survival analysis and Cox proportional hazards models. Sensitivity analyses included subgroup analyses to assess the robustness of findings and interaction tests to explore potential effect modifiers.ResultsThe median age of participants was 59 years, with females accounting for 54.8% of the cohort. Over a median follow‐up duration of 171 months, 10 585 participants developed IDD. In unadjusted Cox regression analyses, compared to the normal group, the hazard ratios (HRs) for IDD were 1.51 (95% CI: 1.41–1.61) in the probable sarcopenia group and 1.47 (95% CI: 1.14–1.90) in the confirmed sarcopenia group. After adjusting for multiple covariates, the corresponding HRs were 1.35 (95% CI: 1.26–1.44) and 1.41 (95% CI: 1.10–1.80), respectively. These associations remained consistent across subgroup analyses. Notably, in BMI‐stratified analyses, individuals with sarcopenia and a BMI &gt; 25 had a higher risk of IDD (HR: 1.88; 95% CI: 1.31–2.71) compared to those with BMI ≤ 25 (HR: 1.51; 95% CI: 1.06–2.16), with a significant interaction (<jats:italic>p</jats:italic> &lt; 0.001).ConclusionsSarcopenia is associated with an increased risk of IDD, particularly in overweight or obese individuals. Regular assessment of muscle strength and mass, along with promoting physical activity and adequate nutritional interventions in ageing populations, may help prevent sarcopenia and delay the onset of IDD.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"9 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282687","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":"Impact of Annual Dry Weight Changes on Mortality and Cardiovascular Outcomes in Patients Undergoing Haemodialysis","authors":"Yoosun Joo, Jihoon Park, Yang‐Gyun Kim, Sang‐Ho Lee, Ju‐Young Moon, Soo‐Young Yoon, Hyeon Seok Hwang, Jihyun Baek, Dong‐Young Lee, Gang Jee Ko, Min‐Jeong Lee, Seok Hui Kang, Su Woong Jung","doi":"10.1002/jcsm.70100","DOIUrl":"https://doi.org/10.1002/jcsm.70100","url":null,"abstract":"BackgroundWhile obesity confers a survival advantage, weight loss adversely affects the survival of patients undergoing haemodialysis. However, given the limited information regarding its long‐term effects on mortality and cardiovascular events, the health benefits of weight gain remain uncertain, particularly in Asian patients undergoing haemodialysis.MethodsIn a prospective multicentre cohort of patients undergoing haemodialysis in South Korea, patients whose dry weight was recorded at baseline and after 1 year were analysed. Patients were stratified into five groups according to annual dry weight change: stable (−2.0% to 1.9%, <jats:italic>n</jats:italic> = 245), mild (2.0% to 6.9%, <jats:italic>n</jats:italic> = 92) and moderate (≥ 7.0%, <jats:italic>n</jats:italic> = 20) dry weight gain and mild (−5.0% to −2.1%, <jats:italic>n</jats:italic> = 91) and moderate (&lt; −5.0%, <jats:italic>n</jats:italic> = 77) dry weight loss. The associations of annual dry weight change with physical function and health‐related quality of life were examined using cross‐sectional analysis. The impact of annual dry weight changes on all‐cause mortality and a composite of major adverse cardiovascular events (MACEs), defined as myocardial infarction, unstable angina, ischaemic stroke and peripheral artery disease requiring revascularization, was assessed in a longitudinal cohort of 525 individuals.ResultsIn cross‐sectional analysis, patients with diminished physical ability had a higher frequency of dry weight fluctuations. In longitudinal analysis, the mean age of the study participants was 59.9 years, and 62.3% were men. During a median follow‐up of 3.1 years, death and MACE occurred in 105 (20.0%) and 31 (5.9%) patients, respectively. The risk of all‐cause mortality was higher in patients with moderate dry weight gain or loss than in those with stable dry weight (adjusted hazard ratio [aHR] for moderate weight gain, 2.22; 95% confidence interval [CI], 0.96–5.13; <jats:italic>p</jats:italic> = 0.06; and aHR for moderate weight loss, 1.78; 95% CI, 1.07–2.95; <jats:italic>p</jats:italic> = 0.03). The risk of MACE was significantly higher in patients with weight gain (including mild and moderate) than in those with a stable dry weight (aHR, 3.02; 95% CI, 1.32–6.88; <jats:italic>p</jats:italic> = 0.009). Specifically, the increased risk of all‐cause mortality attributable to moderate dry weight gain was limited to patients with obesity, whereas that for moderate dry weight loss was limited to patients with a normal body mass index.ConclusionModerate weight gain and loss were differentially associated with lower survival among patients undergoing haemodialysis, with the former in patients with obesity and the latter in normal‐weight patients. Particularly, dry weight gain increased the risk of cardiovascular events.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"28 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282686","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":"Subcutaneous Adipose Tissue Radiation Attenuation Is Associated With Increased 1-Year Mortality in Polytrauma Patients.","authors":"Leanne L G C Ackermans,Jasper C Stokroos,David P J Van Dijk,Bjorn Winkens,Martijn Poeze,Leonard Wee,Ralph Brecheisen,Steven M W Olde Damink,Jan A Ten Bosch,Taco J Blokhuis","doi":"10.1002/jcsm.13743","DOIUrl":"https://doi.org/10.1002/jcsm.13743","url":null,"abstract":"BACKGROUNDPolytrauma patients with an Injury Severity Score (ISS) ≥ 16 have a high mortality rate. Early identification of patients at risk of mortality is key. Different risk stratification models are available; however, body composition on third lumbar computed tomography (L3 CT) is not routinely used. The aim of this study is to determine the effect of CT body composition on 1-year mortality in adult polytrauma patients.METHODSBody composition analysis (L3 CT) was performed on 593 adult polytrauma patients. The associations with 1-year mortality were assessed using uni- and multivariable logistic regression analysis. As a sensitivity analysis, 1-year mortality was analysed using Kaplan-Meier survival curves, log-rank tests and Cox regression.RESULTSThe study population was predominantly male (69.5%), with a mean age of 55 (±20) years and an average BMI of 25.34 kg/m2 (±4.07). Comorbidities were present in 327 (55.4%) patients, with an average Charlson Comorbidity Index (CCI) of 2.07 points (±2.1). The mean ISS score was 27.59 (±11.06); 323 (54.5%) patients had an ISS ≥ 25 points. Age, CCI, ISS, skeletal muscle index and skeletal muscle radiation attenuation (OR 1.053, 5.713, 3.711, 0. 563 and 0.533, respectively; p < 0.001), subcutaneous adipose tissue radiation attenuation (SATRA OR 1.253, p = 0.028) and visceral adipose tissue index (OR 1.242, p = 0.038) were significantly associated with 1-year mortality. In multivariable logistic regression, age, ISS and SATRA remained statistically significantly associated with 1-year mortality (OR 1.062, p < 0.001; OR 4.761, p < 0.001; OR 1.396, p = 0.009).CONCLUSIONSThis study demonstrated that subcutaneous adipose tissue radiation attenuation on emergency trauma CT scans is significantly associated with 1-year mortality in adult polytrauma patients. Additionally, we found a significant effect of age and ISS on 1-year mortality. Incorporating body composition analysis could lead to a better selection of patients at risk for 1-year mortality and aid in treatment decision-making.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"79 1","pages":"e13743"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277168","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":"Peripheral Thyroid Hormones, Inflammatory and Skeletal Muscle Indexes in Advanced Cervical Cancer Treated With Cemiplimab.","authors":"Valentina Tuninetti,Elisa Virano,Amedeo Calvo,Vittoria Carbone,Carmela Pisano,Monika Ducceschi,Giacinto Turitto,Giuseppa Scandurra,Maria Cristina Petrella,Valeria Forestieri,Massimo Petracchini,Alessandra Bianco,Raffaella Cioffi,Mara Mantiero,Eleonora Paluzzi,Maria Grazia Distefano,Olga Martelli,Sandro Pignata,Vincenzo Formica,Fotios Loupakis,Giorgio Valabrega","doi":"10.1002/jcsm.70101","DOIUrl":"https://doi.org/10.1002/jcsm.70101","url":null,"abstract":"BACKGROUNDA low fT3/fT4 ratio has been associated with poorer prognosis in several diseases. Inflammatory indexes (IIs) and the skeletal muscle index (SMI) are established prognostic factors in various cancer types. However, their interplay and individual contributions to the prognosis of cervical cancer remain unclear. This study aimed to evaluate the impact of these biomarkers on survival outcomes in cervical cancer patients treated with innovative immunotherapy.METHODSThis retrospective study included 101 patients with cervical cancer treated with cemiplimab at 12 Italian oncology centres. Patients with thyroid comorbidities or missing fT3/fT4 ratio data were excluded. The primary endpoint was overall survival (OS) in relation to the fT3/fT4 ratio. Secondary endpoints included progression-free survival (PFS) and correlations between the fT3/fT4 ratio, ECOG Performance Status, IIs and SMI.RESULTSAn optimal fT3/fT4 cutoff for OS prediction was identified at 0.29. Median OS was 10.9 months for patients with a low fT3/fT4 ratio, while it was not reached for those with high fT3/fT4 levels (HR = 2.70; 95% CI: 1.17-6.22; p = 0.02). Multivariate analysis confirmed that both the fT3/fT4 ratio and ECOG PS independently influenced OS. Among the IIs analysed, the systemic inflammatory index (SII) demonstrated the strongest correlation with fT3/fT4 levels (OR = 3.82; 95% CI: 1.39-10.50; p = 0.0092). Exploratory analysis also revealed significantly lower SMI values in patients with lower fT3/fT4 ratios (p = 0.034).CONCLUSIONSThis study highlights the prognostic significance of the fT3/fT4 ratio, IIs, and SMI in cervical cancer patients treated with cemiplimab. Given the exploratory nature of these findings, further validation in larger, prospective cohorts is warranted to support their integration into clinical practice and the development of innovative prognostic tools.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"86 1","pages":"e70101"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277201","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":"The Prognostic Role of Frailty and Its Recognition With Simple FRAIL and Fried Frailty Questionnaires in Advanced Cancer Patients.","authors":"Pia Weinländer,Sara Hadzibegovic,Jan Porthun,Lucie Kretzler,Ruben Evertz,Alessia Lena,Laura-Carina Lück,Jonathan L Hella,Ursula Wilkenshoff,Andrea Stroux,Kalliopi Keramida,Anne Letsch,Dominik Paul Modest,Lars Bullinger,Ulrich Keller,Mahir Karakas,Youssef S Abdelwahed,Philipp Attanasio,Ursula Rauch,Carsten Skurk,Wolfram Doehner,Ulf Landmesser,Stephan von Haehling,Markus S Anker","doi":"10.1002/jcsm.70076","DOIUrl":"https://doi.org/10.1002/jcsm.70076","url":null,"abstract":"BACKGROUNDPatients with advanced cancer frequently suffer from frailty associated with vulnerability and adverse outcomes. Our aim was to assess the prevalence of frailty and elucidate the utility of two commonly used frailty questionnaires in an advanced cancer population.METHODSThe Fried Frailty Phenotype (FFP) and Simple FRAIL Questionnaire (SFQ) were assessed in hospitalized patients with mostly advanced cancer. Patients were classified by both questionnaires as frail (3-5 points), pre-frail (1-2 points) and robust (0 points) and followed up for all-cause mortality. Utility was evaluated with correlation and survival analysis.RESULTSFrom 11/2017 to 02/2020, 251 mostly advanced cancer patients (61 ± 13 years, 53% men, BMI 25.3 ± 4.8 kg/m2, 78% cancer stage ≥ 3) were prospectively enrolled. In cancer patients, according to the FFP and SFQ, 17%/13% were frail, 52%/41% prefrail and 31%/47% robust. The correlation between both scores was strong (rs = 0.65, p < 0.001). Both scores were predictors of mortality of cancer patients in univariable and multivariable Cox proportional hazards analyses (multivariable adjusted: per 1 point: FFP: HR 1.36, 95% CI, 1.15-1.61, p < 0.001; SFQ: HR 1.29, 95% CI, 1.09-1.52, p = 0.003-adjustment for age, cancer stage/type, anti-cancer therapy naïve, sex, BMI, CKD and anaemia). The time-dependent multivariable adjusted area under the receiver operating characteristic curve for 6-/24-month survival follow-up for the FFP was 0.78 (95% CI, 0.70-0.86)/0.92 (95% CI, 0.87-0.98) and for the SFQ was 0.79 (95% CI, 0.69-0.88)/0.90 (95% CI, 0.83-0.97).CONCLUSIONFrailty and pre-frailty as assessed by FFP and SFQ are commonly found in advanced stage cancer patients. Both questionnaires have a strong correlation and are associated with all-cause mortality in this population. Since the SFQ is easier and quicker to perform, it can be used remotely, and with untrained staff, it might facilitate earlier preventive measures and initiate further actions to mitigate its impact.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"122 1","pages":"e70076"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277206","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":"Exploration of Fully-Automated Body Composition Analysis Using Routine CT-Staging of Lung Cancer Patients for Survival Prognosis.","authors":"Marc-David Künnemann,Christian Römer,Anne Helfen,Annalen Bleckmann,Marcel Kemper,Walter Heindel,Tobias J Brix,Michael Forsting,Johannes Haubold,Marcel Opitz,Martin Schuler,Felix Nensa,Katarzyna Borys,René Hosch","doi":"10.1002/jcsm.70021","DOIUrl":"https://doi.org/10.1002/jcsm.70021","url":null,"abstract":"BACKGROUNDAI-driven automated body composition analysis (BCA) may provide quantitative prognostic biomarkers derived from routine staging CTs. This two-centre study evaluates the prognostic value of these volumetric markers for overall survival in lung cancer patients.METHODSLung cancer cohorts from Hospital A (n = 3345, median age 65, 86% NSCLC, 40% M1, 40% female) and B (n = 1364, median age 66, 87% NSCLC, 37% M1, 38% female) underwent automated BCA of abdominal CTs ±60 days of primary diagnosis. A deep learning network segmented muscle, bone and adipose tissues (visceral = VAT, subcutaneous = SAT, intra-/intermuscular = IMAT and total = TAT) to derive three markers: Sarcopenia Index (SI = Muscle/Bone), Myosteatotic Fat Index (MFI = IMAT/TAT) and Abdominal Fat Index (AFI = VAT/SAT). Kaplan-Meier survival analysis, Cox proportional hazards modelling and machine learning-based survival prediction were performed. A survival model including clinical data (BMI, ECOG, L3-SMI, -SATI, -VATI and -IMATI) was fitted on Hospital A data and validated on Hospital B data.RESULTSIn nonmetastatic NSCLC, high SI predicted longer survival across centres for males (Hospital A: 24.6 vs. 46.0 months; Hospital B: 13.3 vs. 28.9 months; both p < 0.001) and females (Hospital A: 37.9 vs. 53.6 months, p = 0.008; Hospital B: 23.0 vs. 28.6 months, p = 0.018). High MFI indicated reduced survival in males at both hospitals (Hospital A: 43.7 vs. 28.2 months; Hospital B: 28.8 vs. 14.3 months; both p ≤ 0.001) but showed center-dependent effects in females (significant only in Hospital A, p < 0.01). In metastatic disease, SI remained prognostic for males at both centres (p < 0.05), while MFI was significant only in Hospital A (p ≤ 0.001) and AFI only in Hospital B (p = 0.042). Multivariate Cox regression confirmed that higher SI was protective (A: HR 0.53, B: 0.59, p ≤ 0.001), while MFI was associated with shorter survival (A: HR 1.31, B: 1.12, p < 0.01). The multivariate survival model trained on Hospital A's data demonstrated prognostic differentiation of groups in internal (n = 209, p ≤ 0.001) and external (Hospital B, n = 361, p = 0.044) validation, with SI feature importance (0.037) ranking below ECOG (0.082) and M-status (0.078), outperforming all other features including conventional L3-single-slice measurements.CONCLUSIONCT-based volumetric BCA provides prognostic biomarkers in lung cancer with varying significance by sex, disease stage and centre. SI was the strongest prognostic marker, outperforming conventional L3-based measurements, while fat-related markers showed varying associations. Our multivariate model suggests that BCA markers, particularly SI, may enhance risk stratification in lung cancer, pending centre-specific and sex-specific validation. Integration of these markers into clinical workflows could enable personalized care and targeted interventions for high-risk patients.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"27 1","pages":"e70021"},"PeriodicalIF":8.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787090","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":"The Novel MuRF2 Target SNX5 Regulates PKA Activity Through Stabilization of RI-α and Controls Myogenic Differentiation.","authors":"Ning Li, Jida Hamati, Yi Li, Björn Brinschwitz, Mohamed Ghait, Elisa Martin, Dörte Lodka, Elke Hammer, Britta Fielitz, Uwe Völker, Gunnar Dittmar, Thomas Sommer, Friedrich C Luft, Jens Fielitz","doi":"10.1002/jcsm.70103","DOIUrl":"https://doi.org/10.1002/jcsm.70103","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Muscle RING finger (MuRF) proteins are striated muscle-specific E3 ubiquitin ligases essential for muscle homeostasis. Whereas MuRF1 is well known for its role in muscle atrophy, MuRF2 and MuRF3 contribute to microtubule stabilization, influencing muscle differentiation and function. Their cooperative functions in regulating myogenesis are unclear. This study aimed to identify novel MuRF2 and MuRF3 interaction partners and investigate their function in myogenic differentiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Interaction partners of MuRF2 and MuRF3 were identified using stable isotope labelling with amino acids in cell culture (SILAC), followed by affinity purification and quantitative mass spectrometry (AP-MS). Mechanistic analyses included co-immunoprecipitation, domain mapping, ubiquitination assays, protein stability measurements and endosome isolation. Myogenic differentiation was evaluated by immunocytochemistry, qRT-PCR and western blotting. Functional effects were assessed using CRISPR-Cas9-mediated knockout and siRNA silencing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified sorting nexin 5 (SNX5), a BAR and PX domain-containing retromer component involved in retrograde vesicular transport, as a novel MuRF2 and MuRF3 binding partner. Both coiled-coil domains of MuRF3 were required for SNX5 binding, and the BAR domain of SNX5 mediated interaction with MuRF2 and MuRF3. Immunofluorescence staining demonstrated MuRF3-SNX5 interaction and colocalization on early endosomes along microtubules in myocytes. MuRF2 promoted ubiquitination of SNX5 at lysines 290 and 324, leading to proteasomal degradation, whereas MuRF3 counteracted this effect. Mass spectrometry revealed the protein kinase A regulatory subunit (PKA-RI-α) as cargo of SNX5-coated early endosomes in myocytes. SNX5 knockout (SNX5-KO) reduced RI-α stability in myocytes, enhanced PKA activity and increased HDAC5 degradation via the autophagy-lysosomal pathway, leading to MEF2-mediated upregulation of myostatin. SNX5-KO impaired myogenesis, with significant reductions in myogenin/Myog (p &lt; 0.005), myomaker/Mymk (p &lt; 0.01), myomerger/Mymx (p &lt; 0.005) and MyHC isoforms Myh2 and Myh4 (p &lt; 0.01). Myostatin treatment mimicked the SNX5-KO phenotype, reducing fast-twitch MyHC isoforms Myh1, Myh2, Myh3 and Myh4 (p &lt; 0.05 for all) and significantly lowering Myomaker, Myomerger and MyHC expression throughout differentiation (p &lt; 0.05 for all). Morphologically, myostatin-treated cells were shorter and thinner and had fewer nuclei. Quantification showed reduced differentiation and fusion indices (p &lt; 0.001) and fewer nuclei per myosin-positive cell (p &lt; 0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;MuRF2 and MuRF3 exert opposing effects on SNX5-mediated retrograde transport, influencing PKA signalling and myogenic differentiation. SNX5 stabilizes RI-α within early endosomes, facilitating ordered myogenic differentiation. Our findings expand the known functions of MuRF prote","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"16 5","pages":"e70103"},"PeriodicalIF":9.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278593","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":"Call for standardization in assessment and reporting of muscle and adipose change using computed tomography analysis in oncology: A scoping review","authors":"Pamela N. Klassen,&nbsp;Vera C. Mazurak,&nbsp;Jessica Thorlakson,&nbsp;Stephane Servais","doi":"10.1002/jcsm.13318","DOIUrl":"10.1002/jcsm.13318","url":null,"abstract":"Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta‐analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative‐intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta‐analysis. Studies that measured computed tomography‐defined SM and/or AT change in adult patients during palliative‐intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2/m2, cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex‐specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta‐analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"1918-1931"},"PeriodicalIF":8.9,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524503","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":"Radiation induces long-term muscle fibrosis and promotes a fibrotic phenotype in fibro-adipogenic progenitors","authors":"Nicolas Collao,&nbsp;Donna D'Souza,&nbsp;Laura Messeiller,&nbsp;Evan Pilon,&nbsp;Jessica Lloyd,&nbsp;Jillian Larkin,&nbsp;Matthew Ngu,&nbsp;Alexanne Cuillerier,&nbsp;Alexander E. Green,&nbsp;Keir J. Menzies,&nbsp;Yan Burelle,&nbsp;Michael De Lisio","doi":"10.1002/jcsm.13320","DOIUrl":"10.1002/jcsm.13320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Radiation-induced muscle pathology, characterized by muscle atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro/adipogenic progenitors (FAPs) are required for muscle maintenance and regeneration, while in muscle pathology FAPs are precursors for exacerbated extracellular matrix deposition. However, the role of FAPs in radiation-induced muscle pathology has not previously been explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four-week-old Male CBA or C57Bl/6J mice received a single dose (16 Gy) of irradiation (IR) to a single hindlimb with the shielded contralateral limb (CLTR) serving as a non-IR control. Mice were sacrificed 3, 7, 14 (acute IR response), and 56 days post-IR (long-term IR response). Changes in skeletal muscle morphology, myofibre composition, muscle niche cellular dynamics, DNA damage, proliferation, mitochondrial respiration, and metabolism and changes in progenitor cell fate where assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Juvenile radiation exposure resulted in smaller myofibre cross-sectional area, particularly in type I and IIA myofibres (<i>P</i> &lt; 0.05) and reduced the proportion of type I myofibres (<i>P</i> &lt; 0.05). Skeletal muscle fibrosis (<i>P</i> &lt; 0.05) was evident at 56 days post-IR. The IR-limb had fewer endothelial cells (<i>P</i> &lt; 0.05) and fibro-adipogenic progenitors (FAPs) (<i>P</i> &lt; 0.05) at 56 days post-IR. Fewer muscle satellite (stem) cells were detected at 3 and 56 days in the IR-limb (<i>P</i> &lt; 0.05). IR induced FAP senescence (<i>P</i> &lt; 0.05), increased their fibrogenic differentiation (<i>P</i> &lt; 0.01), and promoted their glycolytic metabolism. Further, IR altered the FAP secretome in a manner that impaired muscle satellite (stem) cell differentiation (<i>P</i> &lt; 0.05) and fusion (<i>P</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study suggests that following juvenile radiation exposure, FAPs contribute to long-term skeletal muscle atrophy and fibrosis. These findings provide rationale for investigating FAP-targeted therapies to ameliorate the negative late effects of radiation exposure in skeletal muscle.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2335-2349"},"PeriodicalIF":8.9,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516219","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}