Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"GDF15 Neutralization Ameliorates Muscle Atrophy and Exercise Intolerance in a Mouse Model of Mitochondrial Myopathy","authors":"Stephen E. Flaherty III, LouJin Song, Bina Albuquerque, Anthony Rinaldi, Mary Piper, Dinesh Hirenallur Shanthappa, Xian Chen, John Stansfield, Shoh Asano, Evanthia Pashos, Trenton Thomas Ross, Srinath Jagarlapudi, Abdul Sheikh, Bei Zhang, Zhidan Wu","doi":"10.1002/jcsm.13715","DOIUrl":"https://doi.org/10.1002/jcsm.13715","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Primary mitochondrial myopathies (PMMs) are disorders caused by mutations in genes encoding mitochondrial proteins and proteins involved in mitochondrial function. PMMs are characterized by loss of muscle mass and strength as well as impaired exercise capacity. Growth/Differentiation Factor 15 (GDF15) was reported to be highly elevated in PMMs and cancer cachexia. Previous studies have shown that GDF15 neutralization is effective in improving skeletal muscle mass and function in cancer cachexia. It remains to be determined if the inhibition of GDF15 could be beneficial for PMMs. The purpose of the present study is to assess whether treatment with a GDF15 neutralizing antibody can alleviate muscle atrophy and physical performance impairment in a mouse model of PMM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The effects of GDF15 neutralization on PMM were assessed using Polg<sup>D257A/D257A</sup> (POLG) mice. These mice express a proofreading-deficient version of the mitochondrial DNA polymerase gamma, leading to an increased rate of mutations in mitochondrial DNA (mtDNA). These animals display increased circulating GDF15 levels, reduced muscle mass and function, exercise intolerance, and premature aging. Starting at 9 months of age, the mice were treated with an anti-GDF15 antibody (mAB2) once per week for 12 weeks. Body weight, food intake, body composition, and muscle mass were assessed. Muscle function and exercise capacity were evaluated using in vivo concentric max force stimulation assays, forced treadmill running and voluntary home-cage wheel running. Mechanistic investigations were performed via muscle histology, bulk transcriptomic analysis, RT-qPCR and western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Anti-GDF15 antibody treatment ameliorated the metabolic phenotypes of the POLG animals, improving body weight (+13% ± 8%, <i>p</i> < 0.0001), lean mass (+13% ± 15%, <i>p</i> < 0.001) and muscle mass (+35% ± 24%, <i>p</i> < 0.001). Additionally, the treatment improved skeletal muscle max force production (+35% ± 43%, <i>p</i> < 0.001) and exercise performance, including treadmill (+40% ± 29%, <i>p</i> < 0.05) and voluntary wheel running (+320% ± 19%, <i>p</i> < 0.05). Mechanistically, the beneficial effects of GDF15 neutralization are linked to the reversal of the transcriptional dysregulation in genes involved in autophagy and proteasome signalling. The treatment also appears to dampen glucocorticoid signalling by suppressing circulating corticosterone levels in the POLG animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447197","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":"The Impact of Radiation Dose on CT-Based Body Composition Analysis: A Large-Animal Study","authors":"Luca Salhöfer, Gregor Jost, Mathias Meetschen, Daniel van Landeghem, Michael Forsting, Denise Bos, Christian Bojahr, Rene Hosch, Felix Nensa, Hubertus Pietsch, Johannes Haubold","doi":"10.1002/jcsm.13741","DOIUrl":"https://doi.org/10.1002/jcsm.13741","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>CT-based body composition analysis (BCA) enables the extraction of biomarkers from routine CT data. The influence of body composition on the prognosis of different patient groups has been highlighted in recent years. Typically, the segmentation of muscle and fat compartments is performed with a thresholding-based subsegmentation, which might be influenced by the image noise as a function of radiation dose. This study was performed to investigate the impact of the radiation dose on a fully automated, volumetric CT-based BCA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this animal study, 20 Göttingen minipigs were subjected to CT scans on six occasions under five different dose settings with gradations compared to the control given in % from volumetric CT dose index (CTDIvol) of the control (5%, 10%, 20%, 40%, control [10.01 mGy]). A database with full dose (FD) and quarter dose (QD) CT scans from The Cancer Imaging Archive served as a human validation cohort. A previously open-source published and validated BCA network was applied to each scan. The following features were extracted as volumes (mL): bone, muscle, subcutaneous adipose tissue (SAT), intermuscular and intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT) and total adipose tissue (TAT). Statistical significance was assessed by a one-way ANOVA with Tukey's multiple comparisons or Kruskal–Wallis with Dunn's post-hoc tests. The correlation between feature volumes in the dose gradations and the control group was analysed using the Spearman or Pearson method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All BCA features remained consistent up to the 10% group and showed no significant differences compared with the control. In the lowest dose group (5%), there were significant differences concerning the muscle (5% = 1295 mL [211 mL], control = 1338 mL [248 mL]; <i>p</i> = 0.032) and VAT volumetry (5% = 353 mL [208 mL], control = 312 mL [204 mL]; <i>p</i> = 0.026) with median differences of −3.13% (muscle) and 12.3% (VAT), respectively. Significant and strong positive correlations were observed between all low-dose groups and the control (<i>r</i> > 0.977, <i>p</i> < 0.001). The human validation analysis yielded constant volumes for every BCA feature with a strong positive correlation (<i>r</i> > 0.933, p < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Fully automated BCA maintains consistent results in various low-dose settings. Significant deviations are only observed after more than 90% dose reduction in the l","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13741","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456050","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":"Plant and Animal Protein Intake and Transitions From Multimorbidity to Frailty and Mortality in Older Adults","authors":"Aitana Vázquez-Fernández, Francisco F. Caballero, Humberto Yévenes-Briones, Ellen A. Struijk, Ana Baylin, Teresa T. Fung, Esther Lopez-Garcia","doi":"10.1002/jcsm.13729","DOIUrl":"https://doi.org/10.1002/jcsm.13729","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Multimorbidity is the most common chronic condition experienced among older adults. It is unknown which amount and source of protein influences the development of frailty and mortality in patients with multimorbidity. We aimed to examine the association of plant and animal sources of protein intake with frailty and mortality among this type of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This longitudinal study included 1868 participants aged ≥ 60 years from the Seniors-ENRICA cohort in Spain with multimorbidity, defined as having 2 or more clinician-diagnosed chronic diseases. Habitual diet was assessed at baseline (2008–2010) with a validated computerized diet history. Participants underwent repeated physical examinations (in 2013, 2015 and 2017) for assessment of frailty (≥ 3 criteria from the frailty phenotype: low physical activity, slow walking speed, muscle weakness, weight loss and exhaustion). All-cause mortality was assessed up to January 2022. Analyses were conducted using Cox proportional hazard models and multistate models adjusted for sociodemographic, lifestyle and other dietary factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean consumption of protein was 90.2 (standard deviation [SD]: 26.8) g/day, which represents 18.7% of the total energy intake and 1.23 (0.39) g per kg of body weight per day. Plant protein represented 6.16% of the energy intake, while animal protein represented 12.5%. During a median follow-up of 12.9 (range: 11.7–13.9) years, we documented 196 incident cases of frailty and 490 deaths; of these mortality cases, 83 individuals died after a frailty diagnosis. Higher intake of total protein was associated with decreased risk of frailty (hazard ratio [HR] for tertile 3 vs. tertile 1: 0.66; 95% confidence interval [CI]: 0.45, 0.96; <i>p</i> trend: 0.03). In multistate models, higher fish protein intake decreased the risk in the progression from multimorbidity to frailty (HR per 1-SD increment: 0.81 [95% CI: 0.68, 0.97]), and higher plant protein decreased the risk of progressing from multimorbidity to mortality (0.86 [0.75, 0.98]). In the progression from frailty to mortality, estimates for total, plant and animal protein showed increased risk (HR for 1 SD increment in total protein: 1.38 [1.05, 1.81]; HR for plant protein: 1.29 [1.01, 1.67]; HR for animal protein: 1.41 [1.04, 1.92]). No significant associations were found between meat protein and dairy protein in any transition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In individuals with multimorbid","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13729","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447108","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":"Low-Magnitude High-Frequency Vibration Attenuates Sarcopenia by Modulating Mitochondrial Quality Control via Inhibiting miR-378","authors":"Yu-Feng Long, Can Cui, Qianjin Wang, Zhen Xu, Simon Kwoon-Ho Chow, Ning Zhang, Ronald Man Yeung Wong, Elvis Chun-Sing Chui, Rebecca Schoenmehl, Christoph Brochhausen, Clinton Rubin, Gang Li, Ling Qin, Da-Zhi Yang, Wing-Hoi Cheung","doi":"10.1002/jcsm.13740","DOIUrl":"https://doi.org/10.1002/jcsm.13740","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia, the age-related decline in muscle mass and muscle strength, significantly contributes to falls, diminished quality of life, and mortality. Although mitochondrial dysfunction is increasingly implicated in sarcopenia, the underlying mechanisms are not fully discovered. Low-magnitude high-frequency vibration (LMHFV), a recommended treatment by the Centers for Disease Control and Prevention (CDC) to reduce fall risk, remains poorly understood of the mechanism on improving skeletal muscle quality. This study aims to investigate whether mitochondrial dysfunction contributes to sarcopenia and evaluate whether LMHFV mitigates sarcopenia by improving mitochondrial homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The relationship between mitochondria dysfunction and sarcopenia using senescence accelerated mice prone 8 (SAMP8) model was investigated, assessing muscle and mitochondria. The effects of LMHFV on muscle and mitochondria were evaluated in SAMP8 mice during sarcopenia progression. The role of miR-378 in muscle and mitochondrial homeostasis were evaluated in SAMP8 mice and transgenic over-expressing miR-378 mice (TG mice). The target gene of miR-378 was investigated by dual-luciferase reporter assay in C2C12 cells. Subsequently, we evaluated the effect of LMHFV on miR-378 using both mouse models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Reduction in muscle strength was observed from the ages of month 8 to 10 in SAMP8 mice (grip strength decreased 27.1%, <i>p</i> = 0.0263; twitch force decreased 29.1%, <i>p</i> = 0.0178; tetanic force decreased 29.9%, <i>p</i> = 0.011), as well as muscle atrophy (cross-section area: 38.3%, <i>p</i> = 0.0121). Mitochondrial morphological deterioration was noticed from month 6 to 10. Mitochondrial homeostasis, including biogenesis, fusion, fission, mitophagy, and ATP production declined from month 6 to 10. Compared to control group at month 10, knocking down miR-378 in SAMP8 mice mitigated sarcopenia (twitch force increased 44.3%, <i>p</i> = 0.0023; tetanic force increased 51.9%, <i>p</i> = 0.0005), improved mitochondrial morphologies (mitochondrial number increased 1.65-fold, <i>p</i> = 0.0023; mitochondrial density increased 1.65-fold, <i>p</i> = 0.0023; mitochondrial relative area increased 9.05-fold, <i>p</i> = 0.0019) along with improved mitochondrial homeostasis. Over-expressing miR-378 in transgenic mice exacerbated muscle atrophy and mitochondrial deterioration significantly. The dual-luciferase reporter assay in C2C12 cells revealed that miR-378 inhibited PGC-1α directivity. LMHFV was found to mitigate sarcopenia by modulating mitochondrial home","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13740","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446769","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":"Mapping Normative Muscle Health Metrics Across the Aging Continuum: A Multinational Study Pooling Data From Eight Cohorts in Japan, Malaysia and Taiwan","authors":"Liang-Kung Chen, Lin-Chieh Meng, Li-Ning Peng, Wei-Ju Lee, Shu Zhang, Yukiko Nishita, Rei Otsuka, Minoru Yamada, Wen-Harn Pan, Shahrul Bahyah Kamaruzzaman, Jean Woo, Fei-Yuan Hsiao, Hidenori Arai","doi":"10.1002/jcsm.13731","DOIUrl":"https://doi.org/10.1002/jcsm.13731","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The vigour of our musculature wanes as the years advance, and prognosticating the concomitant trajectories throughout the course of life assumes paramount importance for judicious and timely interventions. In the present study, we aimed to establish age- and sex-specific reference centiles for multiple muscle health metrics and reveal the distributions of these metrics throughout the aging process in the Asian population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By using cross-sectional pooled data of community dwellers aged 20 years or older in eight cohorts from Taiwan, Japan and Malaysia, normative values for muscle health metrics (calf circumference (cm), relative appendicular skeletal muscle (RASM) (kilogram per square metre), body mass index (BMI)–adjusted appendicular skeletal muscle mass (kilogram/(kilogram per square metre)), handgrip strength (kilogram), five-time chair stand (seconds) and gait speed (metre per second)) in men and women, categorized by age groups, are calculated. The mean values, along with the 5th, 25th, 50th, 75th and 95th percentiles of these muscle health metrics, are also delineated for both sexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 34 265 (16 164 men, 18 101 women) participants from eight cohorts, calf circumference declined in age groups from 60 years onward. RASM values declined from the 50s in men but were stable in women until the 80s. ASM/BMI values showed declines in older age groups for both sexes. Handgrip strength declined similarly from 40 years of age in both sexes. Five-time chair stand performance declined from the 30s. Gait speed peaked at 1.6 m/s in men in their 50s and then declined, while it declined in women in their 60s. The inflection points for decline differed by metric and sex. The 20th percentile cutoffs for individuals aged 65–69 years were as follows: calf circumference, 33.0 cm (men) and 31.5 cm (women); RASM, 7.0 kg/m<sup>2</sup> (men) and 5.5 kg/m<sup>2</sup> (women); ASM/BMI, 0.78 kg/(kg/m<sup>2</sup>) (men) and 0.56 kg/(kg/m<sup>2</sup>) (women); handgrip strength, 30.4 kg (men) and 18.1 kg (women); five-time chair stand, 9.4 s (men) and 10.0 s (women); and gait speed, 0.9 m/s (both). Those in the fifth percentile of all muscle health metrics faced earlier declines than their 95th percentile counterparts did, highlighting the critical roles in identifying these high-risk groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The pooled analysis of eight Asian cohorts clearly outlined the age-related changes in various musc","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446770","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":"SIRT6 Ameliorates Cancer Cachexia–Associated Adipose Wasting by Suppressing TNFR2 Signalling in Mice","authors":"Kang Xu, Yida Wang, Fang Wang, Yannan Guo, Yu Ren, Vivien Low, Sungyun Cho, Qingfei Liu, Ying Qiu, Xue Li, Kang Yu, Zhongchi Li, Zhao Wang","doi":"10.1002/jcsm.13734","DOIUrl":"https://doi.org/10.1002/jcsm.13734","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cachexia is a wasting syndrome associated with imbalanced energy metabolism and loss of adipose and muscle tissues and contributes to morbidity and mortality in ageing as well as in patients with severe chronic diseases, including cancer. At present, there are no treatments addressing cachexia that have reached validation to be used in the clinic. In this study, we investigate the protective role of SIRT6, an important regulator of energy homeostasis and health preservation, against Lewis lung carcinoma (LLC)–induced cachexia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SIRT6 levels of serum from gastric cancer patients (<i>n</i> = 22, 65.27 ± 12.50 years old, 40.9% females) and healthy controls (<i>n</i> = 22, 63.50 ± 10.77 years old, 45.4% females) were measured to evaluate the correlation between circulating SIRT6 levels and cancer cachexia development. Ten-week-old SIRT6 transgenic (TG) and wild type (WT) male mice injected with LLC cells (1.5 × 10<sup>6</sup> per mouse) were used to investigate the protective effects of SIRT6 on cachexia-associated adipose browning and lipolysis and the underlying mechanisms. We explored the effect of SIRT6 on LLC-conditioned medium induced lipolysis in mature adipocytes, differentiated from primary mouse embryonic fibroblasts (MEFs). We evaluated the in vitro effect of a SIRT6 activator by treatment of MDL800.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SIRT6 concentrations were significantly higher in non-cachectic cancer patients (3.41 ± 0.30 ng/mL) compared to cachectic cancer patients (3.20 ± 0.23 ng/mL, <i>p</i> < 0.01), suggesting the negative correlation between SIRT6 level and cachexia in patients with cancer. SIRT6 overexpression significantly ameliorated tumour-induced wasting and energy expenditure in white adipose tissues (eWAT mass loss: 66% in WT vs. 32% in TG; iWAT mass loss: 69% in WT vs. 40% in TG) through suppression of browning and lipolysis. In LLC-induced cachexia, tumour necrosis factor-α receptor 2 (TNFR2) mediated the inhibition of SIRT6 on lipolytic signalling, because the difference in lipolysis between the WT and SIRT6 knockout group was almost eliminated by TNFR2 neutralizing antibody. Increased serum TNFR2 concentration was found in cachectic cancer patients (690.41 pg/mL in non-cachectic vs. 1166.98 pg/mL in cachectic patients, <i>p</i> < 0.05). A selective SIRT6 pharmaceutical activator, MDL800, could completely reverse LLC-induced lipolysis in adipocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found an unexpected be","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13734","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446735","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 Gain Among Cancer Patients Receiving Chemotherapy—Facts and Numbers","authors":"Muhammad Shahzeb Khan,&nbsp;Javed Butler,&nbsp;Markus Anker","doi":"10.1002/jcsm.13694","DOIUrl":"https://doi.org/10.1002/jcsm.13694","url":null,"abstract":"<p>Cachexia affects up to 60% of patients with lung cancer, with its prevalence rising up to 80% in advanced stages of disease. In approximately 20% of cases, it is the primary cause of mortality. Five studies, including a total of 4467 patients, across range of cancer types reported data on weight gain in cancer patients undergoing chemotherapy. Across all five studies, an average of 18.3% of patients experienced weight gain &gt; 5% (816 out of 4467 patients). The frequency of weight gain &gt; 5% was highest among breast cancer patients, 18.9% in Pedersini et al (<i>n</i> = 169) and 33.0% in Sella et al (<i>n</i> = 687). In NSCLC patients, weight gain was reported in 18.3% in patients in Patel et al (<i>n</i> = 2301) and 11.7% in Roeland et al (<i>n</i> = 1030). In contrast, colorectal cancer patients showed only 5.7% of weight gain &gt; 5% (Zutphen et al, <i>n</i> = 280). Additionally, weight loss &gt; 5% was reported in 15.1% of breast cancer patients and 28.3% of colorectal cancer patients. Despite weight loss being quantified as a common endpoint in clinical trials focused on cancer cachexia, there is limited data on the impact of weight gain as a marker of a positive outcome among cancer patients. Studies have shown that weight gain of more than 5% within 3 months in NSCLC patients can be associated with improvement in overall survival (OS) and progression-free survival (PFS) scores. In this post hoc analysis by Roeland et al., the authors defined different percentage cut-off values for maximum weight gain among patients with non–small cell lung cancer within 3 months of starting platinum-based chemotherapy. Among all categories, namely, weight gain &gt; 0%, &gt; 2.5% and &gt; 5%, a significant benefit in overall and progression-free survival was seen and was comparable among all groups. These findings highlight the clinical significance of incorporating strategies that encourage weight gain and to prevent weight loss at the least among cancer patients. Along with further delving into the prognostic value of weight gain and developing methods to encourage this response among cancer patients, future studies should use standardized assessment tools to identify weight gain that could be attributed to underlying pathologic processes such as oedema and congestion. We also suggest that monitoring and reporting of weight changes should be done in all cancer trials.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446690","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":"Changes in Protein Metabolism and Early Development of Sarcopenia in Mice With Cholestatic Liver Disease","authors":"Ottavia Agrifoglio,&nbsp;Solvig Görs,&nbsp;Quentin Sciascia,&nbsp;Zeyang Li,&nbsp;Elke Albrecht,&nbsp;Sophie Achilles,&nbsp;Meike Statz,&nbsp;Manuela Bastian,&nbsp;Tobias Lindner,&nbsp;Karen Friederike Gauß,&nbsp;Sarah Rohde,&nbsp;Karen Rischmüller,&nbsp;Peggy Berlin,&nbsp;Georg Lamprecht,&nbsp;Robert Jaster,&nbsp;Cornelia C. Metges,&nbsp;Luise Ehlers","doi":"10.1002/jcsm.13737","DOIUrl":"https://doi.org/10.1002/jcsm.13737","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;Sarcopenia is a frequent complication of liver cirrhosis. Here, we chose a mouse model of cholestatic liver disease (CLD) to gain mechanistic insights into the development of sarcopenia from the earliest stages of chronic liver injury. Particular attention was paid to protein metabolism, metabolite profiles, and mediators of CLD-induced muscle wasting.&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;Male C57BL/6 J mice underwent bile duct ligation (BDL), sham surgery, or served as untreated controls. The observation phase lasted from the preoperative stage to postoperative day 14. Metabolic cage experiments were performed to determine the nitrogen balance (N-BAL), nitrogen metabolite profiles, and total energy expenditure (TEE) using doubly labelled water. The fractional protein synthesis rate (FPSR) was assessed using &lt;sup&gt;2&lt;/sup&gt;H&lt;sub&gt;5&lt;/sub&gt;-ring-phenylalanine. Plasma concentrations of inflammatory markers, metabolites, and enzymes associated with liver damage were investigated. Muscle strength and volume were assessed using a grip strength meter and MRI, respectively. Gene expression was analysed by real-time PCR.&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;BDL caused CLD with necroses and inflammation, increased bilirubin (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and conjugated bile acids (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), and reduced food intake (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and body weight (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001; each vs. sham). Compared to controls, BDL mice showed lower N-BAL (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), reduced TEE (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), and lower FPSR in the liver (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and quadriceps muscle (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Arginine was the only plasma amino acid that was diminished after BDL compared to controls and sham treatment (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Reduced muscle strength was observed as early as d3/d4 after BDL (&lt;i&gt;p&lt;/i&gt; &lt; 0.001; vs. sham), while muscle volume decreased from d6 to d13 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In quadriceps muscle, a lower nuclei-to-fibre ratio (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and elevated 1-methyl-histidine (1-MH) (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) were detected, whereas 3-MH was increased in the urine of BDL mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.001; each vs. sham). The quadriceps muscle of BDL mice contained higher mRNA levels of atrophy-associated genes (&lt;i&gt;Trim63&lt;/i&gt;: &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, &lt;i&gt;Fbxo32&lt;/i&gt;: &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and &lt;i&gt;Mstn&lt;/i&gt; (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), but lower levels of genes involved in mitochondrial function (&lt;i&gt;Cpt-1b&lt;/i&gt;: &lt;i&gt;p&lt;/i&gt; &lt; 0.05, &lt;i&gt;Pgc-1α&lt;/i&gt;: &lt;i&gt;p&lt;/i&gt; &lt; 0.01; each vs. sham). In the plasma of BDL mice, elevated protein levels of TNF receptor-1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and HGF-1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) were observed, while myo","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13737","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446823","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":"Leg Muscle Volume, Intramuscular Fat and Force Generation: Insights From a Computer-Vision Model and Fat-Water MRI","authors":"Andrew C. Smith,&nbsp;Javier Muñoz Laguna,&nbsp;Eddo O. Wesselink,&nbsp;Zachary E. Scott,&nbsp;Hazel Jenkins,&nbsp;Wesley A. Thornton,&nbsp;Marie Wasielewski,&nbsp;Jordan Connor,&nbsp;Scott Delp,&nbsp;Akshay S. Chaudhari,&nbsp;Todd B. Parrish,&nbsp;Sean Mackey,&nbsp;James M. Elliott,&nbsp;Kenneth A. Weber II","doi":"10.1002/jcsm.13735","DOIUrl":"https://doi.org/10.1002/jcsm.13735","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;Maintaining skeletal muscle health (i.e., muscle size and quality) is crucial for preserving mobility. Decreases in lower limb muscle volume and increased intramuscular fat (IMF) are common findings in people with impaired mobility. We developed an automated method to extract markers of leg muscle health, muscle volume and IMF, from MRI. We then explored their associations with age, body mass index (BMI), sex and voluntary force generation.&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 trained (&lt;i&gt;n&lt;/i&gt; = 34) and tested (&lt;i&gt;n&lt;/i&gt; = 16) a convolutional neural network (CNN) to segment five muscle groups in both legs from fat-water MRI to explore muscle volume and IMF. In 95 participants (70 females, 25 males, mean age [standard deviation] = 34.2 (11.2) years, age range = 18–60 years), we explored associations between the CNN measures and age, BMI and sex, and then in a subset of 75 participants, we explored associations between CNN muscle volume, CNN IMF and maximum plantarflexion force after controlling for age, BMI and sex.&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 CNN demonstrated high test accuracy (Sørensen–Dice index ≥ 0.87 for all muscle groups) and reliability (muscle volume ICC&lt;sub&gt;2,1&lt;/sub&gt; ≥ 0.923 and IMF ICC&lt;sub&gt;2&lt;/sub&gt;,&lt;sub&gt;1&lt;/sub&gt; ≥ 0.815 for all muscle groups) compared to manual segmentation. CNN muscle volume was positively associated with BMI across all muscle groups (&lt;i&gt;p&lt;/i&gt; ≤ 0.001) but not with age (&lt;i&gt;p&lt;/i&gt; ≥ 0.406). CNN IMF was positively associated with age for all muscle groups (&lt;i&gt;p&lt;/i&gt; ≤ 0.015), and CNN IMF was positively associated with BMI for all muscle groups (&lt;i&gt;p&lt;/i&gt; ≤ 0.043) except the right deep posterior compartment (&lt;i&gt;p&lt;/i&gt; = 0.130). Males had greater CNN volume of all muscle groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) except the left and right gastrocnemius (&lt;i&gt;p&lt;/i&gt; ≥ 0.067). Gastrocnemius CNN IMF was greater in females (&lt;i&gt;p&lt;/i&gt; ≤ 0.043). Plantarflexion force was positively associated with lateral compartment, soleus and gastrocnemius CNN volume (&lt;i&gt;p&lt;/i&gt; ≤ 0.025) but not with CNN IMF (&lt;i&gt;p&lt;/i&gt; ≥ 0.358).&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;Computer-vision models combined with fat-water MRI permits the non-invasive, automatic assessment of leg muscle volume and IMF. Associations with age, BMI and sex are important when interpreting these measures. Markers of leg muscle health may enhance our understanding of the relationship between muscle health, force generation and mobility.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447190","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":"Hand Grip Strength Cut-Off Points as a Discriminator of Sarcopenia and Sarcopenic Obesity: Results from the ELSA-Brasil Cohort","authors":"Clarice Alves Santos,&nbsp;Helena Fraga Maia,&nbsp;Francisco José Gondim Pitanga,&nbsp;Maria da Conceição Chagas de Almeida,&nbsp;Maria de Jesus Mendes da Fonseca,&nbsp;Estela Mota Leão de Aquino,&nbsp;Letícia de Oliveira Cardoso,&nbsp;Rosane Harter Griep,&nbsp;Sandhi Maria Barreto,&nbsp;Claudia Kimie Suemoto,&nbsp;Paulo Lotufo,&nbsp;Isabela Bensenor,&nbsp;Sheila Maria Alvim de Matos","doi":"10.1002/jcsm.13723","DOIUrl":"https://doi.org/10.1002/jcsm.13723","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;Hand grip strength (HGS) may represent an epidemiologically relevant alternative as an initial screening tool for sarcopenia and sarcopenic obesity. However, no study evaluated the performance capacity of HGS compared to other biomarkers in discriminating these conditions in adults.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The study aimed to evaluate the performance of HGS as discriminator of sarcopenia and sarcopenic obesity, compared to urinary biomarkers of creatinine and potassium in 24 h for Brazilian adults.&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;Cross-sectional study. Women (&lt;i&gt;n&lt;/i&gt; = 5431) and men (&lt;i&gt;n&lt;/i&gt; = 6351) aged 38–79 years who participated in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) at second follow-up of the cohort (2012–2014). The area under the receiver operating characteristic curve (AUC) and the respective 95% confidence intervals were calculated for men and women in different age groups to assess the performance of HGS as a discriminator of sarcopenia and sarcopenic obesity, compared to the biomarkers of potassium and creatinine in urine in 24 h. The outcomes were classified based on the skeletal muscle mass index (BMI/height&lt;sup&gt;2&lt;/sup&gt;) and fat percentage, estimated from the bioimpedance analysis data. Sensitivity, specificity and Brier score were calculated for each estimated HGS cut-off point.&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;It can be observed that 18.20% (15.51% women; 21.34% men) of the population showed a decline in skeletal muscle mass (sarcopenia). Of this total, 11.61% (10.52% women; 12.89% men) presented the isolated outcome of sarcopenia and 6.59% (4.99% women; 8.45% men) of sarcopenic obesity. The HGS areas under the ROC Curve ranged from 0.54 (CI = 0.493–0.596) to 0.76 (CI = 0.650–0.878) according to sex and age group. HGS performance compared to biomarkers was significantly higher in virtually all strata and outcomes analysed. The cut-off points that demonstrated greater accuracy and better performance in outcome discrimination were ≤ 42, ≤ 41, ≤ 38 and ≤ 36 kgf among males aged 38–44 years, 45–54 years, 55–64 years and 65–79 years, respectively. For women in the same age groups, HGS cut-offs were ≤ 26, ≤ 23, ≤ 23 and ≤ 21 kgf, respectively.&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;The results suggest that HGS is a good discriminator of sarcopenia and sarcopenic obesity, capable of achieving superior or equal per","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439237","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}