Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Waist-to-Body Mass Index Ratio and Risk of Musculoskeletal Disease in Type 2 Diabetes: A Cohort and PhIP-Seq Analysis.","authors":"Yongze Zhang, Luxi Lin, Lifeng Zheng, Xiaohuang Lin, Zhaowei Xu, Ximei Shen, Lingning Huang, Fengying Zhao, Sunjie Yan","doi":"10.1002/jcsm.70336","DOIUrl":"10.1002/jcsm.70336","url":null,"abstract":"<p><strong>Background: </strong>Musculoskeletal complications in type 2 diabetes (T2DM) are inadequately captured by body mass index (BMI). Waist-to-BMI ratio (WBR) may better reflect adverse body composition. We examined cross-sectional and longitudinal associations between WBR and musculoskeletal disorders in T2DM.</p><p><strong>Methods: </strong>This two-phase study was conducted within an ongoing hospital-based cohort at the First Affiliated Hospital of Fujian Medical University (Fuzhou, China). The cross-sectional analysis included 4157 adults with T2DM recruited between March 2012 and August 2023 (54.3% men; mean age 59.4 ± 10.3 years), using data from their first assessment. Associations of waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), BMI and WBR with osteopenia, sarcopenia, sarcopenic osteopenia (SOs), sarcopenic obesity (SOb) and fractures were evaluated. The prospective cohort comprised a longitudinal subset enrolled between March 2012 and June 2022, ensuring at least 1 year of follow-up prior to administrative censoring in August 2023. A total of 440 individuals (57.0% men; mean age 59.7 ± 9.7 years) were followed for a median of 34.0 months (20.0-57.0). Associations between time-dependent WBR and incident outcomes were assessed using Cox models. A nested exploratory analysis was conducted within the cohort. Thirty participants with extreme annualised WBR change (ΔWBR/yr) were selected. Baseline serum samples collected at enrolment, prior to outcome occurrence, were analysed using phage immunoprecipitation sequencing (PhIP-Seq).</p><p><strong>Results: </strong>Cross-sectionally, WBR was negatively correlated with bone mineral density and appendicular skeletal muscle mass index and positively correlated with osteopenia, sarcopenia, SOs, SOb and fractures (all p < 0.01), whereas BMI, WC, WHtR and WHR showed weaker associations. After adjustment, higher WBR was independently associated with osteopenia (men: OR 1.723, 95% CI 1.614-1.840; women: OR 1.420, 1.348-1.495), sarcopenia (men: OR 4.779, 4.165-5.484; women: OR 2.991, 2.683-3.334), SOs (men: OR 6.261, 5.314-7.377; women: OR 4.336, 3.753-5.010), SOb (men: OR 4.737, 3.975-5.646; women: OR 4.652, 3.715-5.825) and fractures (men: OR 1.236, 1.093-1.397; women: OR 1.103, 1.003-1.213; all p < 0.05). Prospectively, higher time-dependent WBR predicted incident osteopenia (HR 1.365, 95% CI 1.024-1.820), sarcopenia (HR 1.282, 1.086-1.512), SOs (HR 1.408, 1.176-1.686), SOb (HR 1.634, 1.262-2.116) and fractures (HR 1.369, 1.029-1.821). PhIP-Seq analysis identified differential autoantibody reactivity related to muscle structural organisation and cytoskeletal regulation, while bone-related differences were enriched in Wnt signalling and hormone-related pathways.</p><p><strong>Conclusions: </strong>Higher WBR and longitudinal increases were independently associated with osteopenia, sarcopenia, sarcopenic phenotypes and fractures in individuals with T2DM.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 4","pages":"e70336"},"PeriodicalIF":9.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13448775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682878","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":"Electroacupuncture Treatment on Sarcopenia in Patients Undergoing Maintenance Haemodialysis: An Effective Therapy","authors":"Ruoxin Chen, Qinqin Qian, Bin Wang, Ruoyang Chen, Liuping Zhang, Hui Jin, Jun Zhu, Zuolin Li, Jianyun Gao, Hong Liu","doi":"10.1002/jcsm.70345","DOIUrl":"https://doi.org/10.1002/jcsm.70345","url":null,"abstract":"Background Electroacupuncture (EA) treatment has been utilized for recovery from neuromuscular‐related diseases and may play a significant role in the treatment of sarcopenia. This interventional, randomized controlled clinical study aims to explore the efficacy of EA treatment in maintenance haemodialysis (MHD) patients with sarcopenia. Methods Thirty‐six participants with sarcopenia undergoing MHD were randomly divided into the control group and the EA group. The participants in the EA group received a total of 24 treatments, each lasting 30 min, and were administered three times per week. Participants in the control group were instructed to continue their current lifestyle and treatment plans. The assessments were conducted at baseline and after 8 weeks. Statistical analysis was performed using two‐way analysis of covariance (ANCOVA) adjusted according to gender and baseline values. Repeated measures analysis of variance (ANOVA) was used to assess EA effects, reporting main effects and the time × group interaction with partial eta squared (η <jats:sup>2</jats:sup> <jats:italic>p</jats:italic> ) effect sizes. The primary outcome was 6‐m gait speed; the secondary outcomes were skeletal muscle mass index (SMI) and handgrip strength. Fasting blood samples were collected, and serum metabolomics using the liquid chromatography–mass spectrometry method was employed to reveal metabolic changes. Results One participant from the EA group dropped out, and 35 participants were included in the analysis, aged (59.06 ± 11.69) years, including 22 men and 13 women. After intervention, the 6‐m gait speed of the EA group increased (Δ = 0.10 ± 0.08; <jats:italic>p</jats:italic> &lt; 0.001), whereas that of the control group decreased (Δ = −0.06 ± 0.09; <jats:italic>p</jats:italic> = 0.018). The handgrip strength of the EA group increased (Δ = 0.68 ± 0.98; <jats:italic>p</jats:italic> = 0.011), whereas that of the control group decreased (Δ = −0.76 ± 1.19; <jats:italic>p</jats:italic> = 0.015). The SMI in the EA group increased (Δ = 0.19 ± 0.22; <jats:italic>p</jats:italic> = 0.003), although there was no significant difference in the control group. No serious adverse events were observed during the EA treatment. The results of serum metabolomics indicated that a total of 127 differentially expressed metabolites were identified ( <jats:italic>p</jats:italic> &lt; 0.05, VIP &gt; 1), including 35 up‐regulated metabolites and 92 down‐regulated metabolites. KEGG pathway enrichment analysis showed that glycerophospholipid metabolism, linoleic acid metabolism and other pathways related to lipid metabolism were significantly changed. Conclusions EA treatment was an effective therapy for sarcopenia in patients undergoing MHD. Its therapeutic effect may be related to the positive regulation of systemic metabolism (including amino acid and lipid profiles).","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"68 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498736","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":"Cancer IDO1-Mediated Tryptophan-Kynurenine Metabolic Reprogramming to Drive Skeletal Muscle Atrophy and Cachexia Acceleration.","authors":"Leng Han,Lingjie Jing,Xinting Zhu,Ciqin Li,Lu Bai,Yang Fang,Yuxuan Zhou,Dingyuan Bai,Jin Lu,Yonglong Han,Cheng Guo,Shumin Zhou,Quanjun Yang","doi":"10.1002/jcsm.70295","DOIUrl":"https://doi.org/10.1002/jcsm.70295","url":null,"abstract":"BACKGROUNDCancer cachexia is a debilitating syndrome characterized by severe skeletal muscle wasting, which significantly impairs patient quality of life and survival. Indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme in tryptophan (Trp) metabolism, is often upregulated in cancers, but its specific role in driving lung cancer-associated cachexia remains inadequately defined. This study investigated the mechanistic role of Ido1 in cancer cachexia and evaluated the therapeutic potential of its inhibition.METHODSWe established Lewis lung carcinoma (LLC) models in C57BL/6 mice using wild-type, Ido1-overexpressing (Ido1-OE) and Ido1-knockout (Ido1-KO) cells. Muscle mass, tumour growth and metabolic changes were assessed in vivo. Transcriptomic and targeted metabolomic analyses were performed on muscle and serum samples. In vitro, we examined the effects of tumour-conditioned media, the Trp metabolite kynurenine (Kyn) and Trp supplementation on C2C12 myotube atrophy. In vivo experiments verified the efficacy of the Ido1 inhibitor palmatine hydrochloride (PAL). Molecular pathways were analysed via western blot and qPCR.RESULTSCompared to LLC mouse models, Ido1-OE significantly exacerbated tumour growth and cachexia, leading to a significant decrease in lean body weight, gastrocnemius and tibialis anterior muscle weights (p &lt; 0.01, p &lt; 0.0001, p &lt; 0.001). Gastrocnemius muscle fibre cross-sectional area significantly decreased in the Ido1-OE group (p &lt; 0.0001). Transcriptomic analysis revealed that Ido1-OE activated pro-inflammatory and protein degradation pathways (upregulating MuRF1/Atrogin1, p &lt; 0.05) while suppressing anabolic signalling pathways (oestrogen pathways, p &lt; 0.01). Metabolomics analysis revealed unique metabolic signatures in Ido1-OE mice: Trp depletion and Kyn accumulation. In vitro experiments demonstrated that Ido1-OE enhanced LLC cell proliferation and migration capabilities (p &lt; 0.0001, p &lt; 0.0001). Tumour-conditioned medium (TCM) derived from Ido1-OE tumours significantly induced C2C12 myotube atrophy (p &lt; 0.01). Similarly, direct treatment with Kyn led to dose-dependent muscle fibre shrinkage, with significant atrophy observed at 30 μM (p &lt; 0.01) and 100 μM (p &lt; 0.0001). Notably, the myotube atrophy induced by Kyn was significantly reversed by the addition of supplemental Trp (p &lt; 0.0001). Compared with the Ido1-OE group, PAL treatment reduced gastrocnemius and tibialis anterior atrophy (p &lt; 0.01; p &lt; 0.05). Mechanistically, PAL inhibited the mRNA expression levels of MuRF1/Atrogin1 (p &lt; 0.0001, p &lt; 0.001), as well as their corresponding protein levels (p &lt; 0.0001, p &lt; 0.0001). Furthermore, PAL restored the phosphorylation level of mTOR (p &lt; 0.001), as well as the mRNA expression of myosin heavy chain (p &lt; 0.01).CONCLUSIONSOur findings demonstrate that Ido1 accelerates muscle atrophy and cancer cachexia by driving a metabolic reprogramming centred on the Trp-Kyn pathway. Pharmacological inhibition of Ido1 with PAL effectively miti","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"21 1","pages":"e70295"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735439","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":"First Evaluation of Ultrafast Ultrasound Coupled With Phrenic Stimulation for Noninvasive Diagnosis of Diaphragm Dysfunction.","authors":"Axel Nierding, Annelyse Nardi, Thomas Similowski, Christian Straus, Jean-Luc Gennisson, Damien Bachasson","doi":"10.1002/jcsm.70323","DOIUrl":"10.1002/jcsm.70323","url":null,"abstract":"<p><strong>Background: </strong>Diaphragm dysfunction is an important and often unrecognized cause of dyspnea. The current gold standard, transdiaphragmatic twitch pressure (Pdi,tw), requires oesophageal and gastric balloon catheters and is infrequently used in routine care. We evaluated whether ultrafast ultrasound descriptors of costal diaphragm during bilateral phrenic magnetic stimulation can provide a noninvasive alternative for assessing diaphragm contractility.</p><p><strong>Methods: </strong>Thirty patients (19 men and 11 women) referred for suspected diaphragm dysfunction (median age 57 [42-63] years) underwent bilateral anterolateral magnetic stimulation with simultaneous ultrafast ultrasound and oesophageal/gastric pressure recordings. Peak diaphragm tissue velocity, acceleration and jerk were extracted. Associations with Pdi,tw were assessed using ridge regression. Diagnostic performance for detecting abnormal Pdi,tw (< 20 cmH₂O) was evaluated using Bayesian receiver operating characteristic (ROC) analysis, including posterior mean AUC and 95% credible intervals. Agreement between predicted and measured Pdi,tw was assessed using Lin's concordance correlation coefficient and Passing-Bablok regression.</p><p><strong>Results: </strong>Twenty four of 30 patients (80%) had abnormal Pdi,tw. Ultrafast ultrasound descriptors correlated with Pdi,tw (Spearman's ρ: velocity 0.77 [95% CI, 0.57-0.89], acceleration 0.70 [95% CI, 0.41-0.87], jerk 0.67 [95% CI, 0.43-0.85]; all p < 0.0001). The multivariable ridge model explained 66% of the variance in Pdi,tw and showed high agreement with measured values (Lin's concordance correlation coefficient = 0.87 [95% CI, 0.75-0.93]). Bayesian ROC analysis demonstrated strong discrimination of diaphragm dysfunction (AUC = 0.91; 95% credible interval [CrI], 0.76-0.98). Using the clinical threshold of 20 cmH₂O, model-predicted Pdi,tw yielded a sensitivity of 75% and specificity of 100%. The optimal velocity threshold for discriminating abnormal Pdi,tw was 10.25 mm·ms^-1 (95% CrI, 6.12-18.58 mm·ms^-1). The corresponding thresholds for acceleration and jerk were 408.6 mm·ms^-2 (95% CrI, 122.6-952.4) and 3073 mm·ms^-3 (95% CrI, 1038.8-11541.4), respectively.</p><p><strong>Conclusions: </strong>Ultrafast ultrasound coupled with magnetic phrenic stimulation provides a feasible, noninvasive, nonvolitional assessment of diaphragm contractility. Diaphragm motion descriptors reliably predicted Pdi,tw and enabled accurate identification of diaphragm dysfunction. These findings support further clinical evaluation and warrant larger multicentre validation studies.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70323"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269493","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":"RAGE Re-Expressed at Myofibre Level Drives Muscle Wasting in Cancer Conditions.","authors":"Sara Chiappalupi, Giulia Gentili, Laura Salvadori, Martina Paiella, Marcello Manfredi, Vittoria Federica Borrini, Kaamashri Mangar, Ann Marie Schmidt, Maurizio Muscaritoli, Francesca Riuzzi, Guglielmo Sorci","doi":"10.1002/jcsm.70302","DOIUrl":"10.1002/jcsm.70302","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cancer cachexia (CC) is a highly debilitating syndrome characterized by loss of body and muscle weight affecting most advanced cancer patients. The receptor for advanced glycation end-products (RAGE) is expressed by several cell types and sustains the inflammatory response in acute and chronic diseases. Total ablation of RAGE (Ager&lt;sup&gt;-/-&lt;/sup&gt; mice) translates into restrained CC and increased survival in tumour-bearing mice. RAGE, which is not expressed in adult healthy myofibres, is re-expressed in atrophying myofibres in cancer conditions. However, the specific contribution of muscular RAGE to CC was unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Using an HSA/Cre-loxP system, we generated a tamoxifen-inducible conditional Ager&lt;sup&gt;mKO&lt;/sup&gt; mouse model in which RAGE is selectively ablated in myofibres. Tamoxifen-treated Ager&lt;sup&gt;mKO&lt;/sup&gt;, Ager&lt;sup&gt;flox&lt;/sup&gt; and Ager&lt;sup&gt;-/-&lt;/sup&gt; mice were subcutaneously injected with Lewis lung carcinoma (LLC) cells, and body changes and survival were monitored until 25 dpi, when histological, molecular and proteomic analyses were performed in tumour-bearing and control mice. Muscle samples of pre-cachectic and cachectic pancreatic cancer patients were analysed to validate the results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with LLC-Ager&lt;sup&gt;flox&lt;/sup&gt; mice, LLC-Ager&lt;sup&gt;mKO&lt;/sup&gt; mice showed reduced (7.5% [p = 0.004] vs. 15.1% [p &lt; 0.0001]) body weight loss, no significant reduction of hind-limb muscle mass and strength and myofibre cross-sectional areas, increased survival (69.2% vs. 42.9% mice alive at 25 dpi) and restrained muscle and serum pro-inflammatory factors. Mechanistically, Ager&lt;sup&gt;mKO&lt;/sup&gt; muscles resist cancer-induced atrophy by maintaining an active Akt-GSK-3β-PGC-1α pathway, and increasing the synthesis of myosin heavy chain (MyHC)-I and -IIa (71.8% [p = 0.008] and 73.9% [p = 0.002] increase, respectively) along with a 76.3% (p = 0.008) increase in hybrid MyHC-I/IIa myofibres. Distinct proteomic signatures characterize muscles of tumour-bearing mice in dependence on RAGE expression, supporting a protective effect of RAGE ablation in muscles. LLC/Ager&lt;sup&gt;mKO&lt;/sup&gt; muscles showed increased amounts of several enzymes involved in glycolysis and glucose catabolism, typical of Warburg metabolism. Noteworthy, muscles of pre-cachectic and cachectic cancer patients showed ~3-fold increase (p &lt; 0.05) in RAGE amounts and reduced Akt-GSK-3β-PGC-1α pathway, compared with healthy control subjects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our data provide evidence that RAGE engagement at myofibre level drives loss of body and muscle weights and inflammation in cancer conditions. RAGE ablation in muscles confers resistance to CC through myofibre remodeling and glycolytic reprogramming. On the clinical side, the overexpression of RAGE is an early event in muscles of cancer patients, suggesting a role for RAGE in the onset of the cachectic syndrome. Thus, the molecular targeting of","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70302"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855771","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":"Not All Weight Loss Is Equal: Towards Muscle-Preserving Therapies in Obesity.","authors":"Joseph D Abraham,Muhammad Shahzeb Khan,Stefan D Anker","doi":"10.1002/jcsm.70298","DOIUrl":"https://doi.org/10.1002/jcsm.70298","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"4 1","pages":"e70298"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753124","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 Health and Prognosis in Patients With Cancer: New Insights.","authors":"Emanuele Cereda, Amanda Casirati, Maria Cristina Gonzalez, Nilian Carla Souza, Carla M Prado, Katherine L Ford, Silvia Fernandes Mauricio, Maria Isabel Toulson Davisson Correia, Paolo Pedrazzoli, Riccardo Caccialanza","doi":"10.1002/jcsm.70292","DOIUrl":"10.1002/jcsm.70292","url":null,"abstract":"<p><strong>Background: </strong>Reduced muscle mass and impaired composition have each been independently associated with worse outcomes in patients with cancer. However, emerging evidence suggests that reduced muscle strength-namely, dynapenia-may be particularly important for prognostication, as it is easier to assess in clinical practice compared to muscle mass. Importantly, muscle mass and composition-as assessed with computed tomography images-may not fully capture key physiological changes and/or reflect whole-body alterations, particularly in patients who remain within the normal range. We investigated the predictive power for mortality of low muscle mass and impaired composition, weight loss (WL) and low strength, as well as their combination, in a cohort of patients with cancer.</p><p><strong>Methods: </strong>Baseline data on muscle mass and radiodensity (Hounsfield units [HU]) at the L3 level-assessed using computed tomography-along with 6-month unintentional WL (relevant if ≥ 10% of usual body weight) and muscle strength by handgrip were pooled for 477 patients with cancer (59.1% male, mean age 61.2 ± 12.8 years) from studies conducted in Brazil, Canada and Italy. Patients were categorized by sex and body mass index-specific cutoffs for low skeletal muscle mass index, low skeletal muscle radiodensity, WL ≥ 10% and low handgrip strength. Patients were followed for at least 12 months until death or censoring.</p><p><strong>Results: </strong>During a median follow-up of 43 months (IQR: 28-83), 188 patients died. Kaplan-Meier analysis showed no survival differences for low skeletal muscle index or low radiodensity, regardless of handgrip strength. Only WL ≥ 10% consistently identified patients with poorer prognosis, independently of low handgrip strength. Fully adjusted Cox's regression models showed an independent association only with WL (HR = 1.56 [95% CI: 1.12;2.16]; p = 0.008) and low handgrip strength (HR = 2.07 [95% CI: 1.47;2.92]; p < 0.001), as well as an increased risk for all low handgrip strength/%WL categories. Mortality risk increased across all low handgrip strength/%WL categories. Among the eight risk groups combining low skeletal muscle mass index, WL ≥ 10% and low handgrip strength, only those including WL ≥ 10% and low handgrip strength were significantly associated with higher mortality. Low skeletal muscle mass index contributed to a worse prognosis only when combined with both WL ≥ 10% and low handgrip strength. Similar results were observed when skeletal muscle radiodensity was used in replacement of skeletal muscle mass index.</p><p><strong>Conclusions: </strong>In patients with cancer, muscle strength and WL were stronger survival predictors than muscle mass and composition, reinforcing their relevancy as easily assessed key markers of muscle health.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70292"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758382","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":"Creatine/Creatinine Ratio and Myostatin as Biomarkers to Monitor Muscle Function in Duchenne Muscular Dystrophy Patients.","authors":"Chiara Degan, Roula Tsonaka, Sharon I de Vries, Nadine A Ikelaar, Menno van der Holst, Hermien E Kan, Erik H Niks, Pietro Spitali","doi":"10.1002/jcsm.70320","DOIUrl":"10.1002/jcsm.70320","url":null,"abstract":"<p><strong>Background: </strong>Duchenne Muscular Dystrophy (DMD) is characterized by progressive muscle wasting leading to early loss of motor function. Functional tests monitor disease progression and serve as clinical trial endpoints but are influenced by maturation in younger patients, high intra-patient variability and patient motivation. Clinical milestones, instead, have been used to identify modifiers of disease progression but are rarely used as primary endpoints since clinical trials are usually too short to capture them. Blood biomarkers, that can reflect disease progression and objectively evaluate treatment responses, offer a valuable alternative. In this study, we investigated whether longitudinal observations of biomarkers myostatin and creatine/creatinine ratio (Cr/Crn) are associated with functional tests, such as 6-min walk test, North Star Ambulatory Assessment (NSAA), 10-m walk-run test velocity (10MWT), Performance of Upper Limb (PUL2.0) and disease milestones like loss of ambulation, overhead reach and hand-to-mouth function.</p><p><strong>Methods: </strong>We used longitudinal data from an observational study on 74 DMD patients followed between 2009 and 2022 with annual visits to the LUMC outpatient clinic, linked to 408 serum samples. Associations between log2-biomarkers, functional tests and clinical milestones were assessed using linear mixed models and time-dependent Cox models. A post-hoc sample size calculation was performed to evaluate whether the biomarkers' lower intra-patient variability (NSAA SD: 0.79, 10MWT SD: 0.88, log2-myostatin and log2-Cr/Crn SDs: 0.57) may improve future clinical trials design.</p><p><strong>Results: </strong>Lower Cr/Crn and higher myostatin levels were associated with better functional performance and a less rapid decline in ambulation, given fixed treatment and BMI. Children with one-unit higher log2-myostatin levels had, on average, 4.73 points higher NSAA and 3.40 points higher PUL2.0 (p-values < 0.001) and were 42% less likely to lose ambulation over the following year. Conversely, children with one-unit lower log2-ratio levels had, on average, 11.40 points higher NSAA and 7.18 points higher PUL2.0 (p-values < 0.001) and were 3.67 times more likely to remain ambulant. We proved that incorporating log2-myostatin and log2-Cr/Crn as endpoints could reduce the required sample size for clinical trials by more than half without compromising statistical power. For instance, to detect a yearly drop of 3 points in the NSAA with 80% power, recruitment requires almost 80 participants in a 1:1 randomized trial, compared to a little more than 50 patients for the respective value of log2-myostatin or log2-Cr/Crn.</p><p><strong>Conclusions: </strong>These findings support the potential of myostatin and Cr/Crn as monitoring biomarkers to enhance trial design and endpoints in clinical and interventional trials for DMD.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70320"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256719","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":"Combined Bisoprolol and Megestrol Acetate Improves Survival and Preserves Cardiac Performance in a Rat Model of Cancer Cachexia.","authors":"Zihao Chen, Siqi Wang, Sandra Palus, Stefan D Anker, Wolfram Doehner, Jochen Springer","doi":"10.1002/jcsm.70313","DOIUrl":"10.1002/jcsm.70313","url":null,"abstract":"<p><strong>Background: </strong>Cancer cachexia is associated with rapid body wasting and cardiac dysfunction. Bisoprolol (BIS) and megestrol acetate (MA) improve selected cachexia phenotypes in the Yoshida AH-130 model, but their combined effects are not defined. We tested reduced-dose combined treatment of BIS and MA (COMB) on survival and organ-specific outcomes.</p><p><strong>Methods: </strong>Male Wistar Han rats (approx. 200 g) received intraperitoneal Yoshida AH-130 hepatoma cells and were treated with placebo (PL, n = 49), BIS (5 mg/kg/day, n = 23), MA (100 mg/kg/day, n = 10) or COMB (BIS 3.75 mg/kg/day + MA 75 mg/kg/day, n = 16). Outcomes included survival, echocardiography (baseline and Day 11), body composition (EchoMRI), terminal tissue weights, food intake and spontaneous locomotor activity.</p><p><strong>Results: </strong>COMB reduced mortality versus placebo (HR = 0.21, p < 0.0001) and had the lowest HR among treatment groups. BIS also reduced mortality versus PL (HR = 0.32, p = 0.0007), whereas MA did not reach statistical significance (HR = 0.49, p = 0.082). COMB did not differ significantly from BIS (HR for COMB vs. BIS = 0.48, p = 0.28) or MA (HR for COMB vs. MA = 0.23, p = 0.06). On Day 11, COMB showed higher LVEF than PL (64.1% ± 9.7% vs. 50.5% ± 12.8%, p < 0.01), higher LV stroke volume (186 ± 49 μL vs. 112 ± 55 μL, p < 0.001) and higher LV mass (515 ± 95 mg vs. 429 ± 65 mg, p < 0.01); changes from baseline were smaller in COMB than PL for LVEF (Δ -12.0% ± 8.9% vs. -24.3% ± 16.2%, p < 0.05) and LV mass (Δ -57 ± 93 mg vs. -137 ± 79 mg, p < 0.05). Body weight, fat mass and lean mass decreased in all groups; COMB showed smaller reductions than PL (p < 0.05) but did not differ from BIS or MA (p > 0.05). BAT weight was higher in COMB than PL (p < 0.001) and higher than BIS (p < 0.001). Food intake on Day 11 was higher than PL in all active groups, and locomotor activity was higher than PL in MA and COMB.</p><p><strong>Conclusions: </strong>COMB reduced mortality versus placebo and showed the lowest HR among treatment groups, accompanied by preserved cardiac performance and a distinct BAT response. Differences versus monotherapy were not statistically significant. Future studies should test optimized dosing and include exposure assessment and tissue profiling to determine benefit over monotherapy and to clarify the basis of the cardiac and BAT phenotypes.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70313"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004010","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":"Effects of Omega-3 Supplementation in Sarcopenia After Bariatric Surgery: A Triple-Blind Randomized Controlled Clinical Trial.","authors":"André Vicente Bigolin, Júlia Iaroseski, Randhall Bruce Carteri, Giovanna Severino Rodrigues, Rafaela de Andrade, Luiz Alberto De Carli, Elisa Loch Razzera, Izabele Vian, Roberta de Almeida da Silva, Antônio Nocchi Kalil, Luis Fernando Ferreira","doi":"10.1002/jcsm.70321","DOIUrl":"10.1002/jcsm.70321","url":null,"abstract":"<p><strong>Background: </strong>Bariatric surgery is an effective treatment for obesity but induces substantial muscle loss, potentially leading to sarcopenia. Omega-3 fatty acids have been associated with improved muscle metabolism, but their effect in the postoperative period of bariatric surgery remains unclear.</p><p><strong>Methods: </strong>A triple-blind randomized clinical trial following CONSORT guidelines. Patients undergoing bariatric surgery were randomly assigned to receive omega-3 supplementation (2000 mg/day of EPA + DHA) or placebo (sunflower oil) for 90 days, including 15 days preoperatively and 75 days postoperatively. Assessments were performed at baseline, 45 days and 105 days after the start of supplementation. Outcomes included skeletal muscle mass (bioelectrical impedance [BIA]), handgrip strength (HGS) and functional performance (timed up and go [TUG] test).</p><p><strong>Results: </strong>Fifty-eight patients were randomized (81% women; mean age 38.2 ± 9.9 years; mean body mass index [BMI]: 41.1 ± 4.6 kg/m²). At baseline, intervention and control groups were comparable in weight (112.7 ± 19.1 vs. 113.0 ± 17.9 kg; p = 0.946), muscle mass (33.5 ± 7.5 vs. 32.5 ± 7.3 kg; p = 0.603), HGS (33.3 ± 9.6 vs. 35.4 ± 10.2 kgf; p = 0.428) and TUG (8.7 ± 3.0 vs. 8.7 ± 1.8 s; p = 0.912). Between baseline and 105 days, muscle mass decreased significantly in both groups (-3.1 ± 0.3 kg; -2.2 ± 0.5 kg; both p < 0.001), without interaction between groups (p = 0.300). HGS remained stable (Δ -0.8 to +2.3 kgf; all p ≥ 0.364), and TUG performance did not change significantly (Δ 0.0-1.1 s; all p ≥ 0.106). Weight loss was marked in both groups (-19.3 ± 1.9 vs. -17.7 ± 2.1 kg; both p < 0.001). The incidence of gastrointestinal symptoms ≥ 3 times/week was similar (34.5% vs. 13.6% at 45 days; p = 0.114). No serious adverse events occurred.</p><p><strong>Conclusions: </strong>Omega-3 supplementation (2000 mg/day) during the perioperative period of bariatric surgery did not prevent muscle mass loss nor improve muscle strength or functional performance within 105 days of follow-up. Although the supplementation was safe and well tolerated, it did not demonstrate efficacy in mitigating early sarcopenia-related outcomes in this population.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT06494566.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70321"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13265123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248228","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}