Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Intramuscular Fat as a Biomarker of Muscle Health: Strengths, Limitations and Open Challenges","authors":"Christopher Spence, Martin Alberto Belzunce, Anna Di Laura, Johann Henckel, Alister J. Hart","doi":"10.1002/jcsm.70389","DOIUrl":"https://doi.org/10.1002/jcsm.70389","url":null,"abstract":"Intramuscular fat (IMF), also known as myosteatosis, refers to the accumulation of lipids within and around skeletal muscle fibres. Excess IMF is increasingly recognised as a sign of poor muscle quality, linked to reductions in strength, power and mobility, and associated with adverse outcomes in metabolic disease, osteoarthritis, cardiovascular diseases and cancer. It is important to note that an increase in intramuscular fat is not always pathological. These associations and the ongoing uncertainty have sparked growing interest in IMF as a biomarker of muscle health beyond muscle mass and cross‐sectional area. This narrative review synthesises current evidence on IMF as a biomarker of muscle health, critically evaluating its definition, measurement, biological variability, responsiveness to intervention and ongoing challenges for clinical application. We first clarify terminology, distinguishing intramyocellular lipids, extramyocellular lipids, intermuscular adipose tissue and subcutaneous adipose tissue. Advances in imaging techniques are assessed: Magnetic resonance imaging and spectroscopy provide accurate compartmental lipid quantification; computed tomography offers practical, reproducible estimates of muscle density; and ultrasound presents an accessible, though operator‐dependent, alternative. Across populations, IMF shows considerable variability: Levels increase with age, differ by sex and ethnicity and have strong associations with adiposity and activity. Normative values are emerging but are lacking standardisation and population‐specific reference ranges. Interventional studies show that IMF is modifiable. Acute endurance exercise reduces intramyocellular lipid stores, while long‐term aerobic and resistance training prevent or lower fat infiltration but increase levels of intramyocellular lipids. Dietary restriction and bariatric surgery reliably decrease IMF but may also cause loss of lean mass without sufficient resistance training or protein intake. Pharmacological therapies, particularly glucagon‐like peptide‐1 receptor agonists such as liraglutide and semaglutide, have recently been shown to lower IMF while enhancing muscle quality, despite some overall muscle reduction. These findings support IMF as a flexible biomarker that indicates intervention success and correlates with functional outcomes including strength, gait speed and insulin sensitivity. Key barriers remain: lack of standardised imaging protocols, no universally defined pathological thresholds and the complex challenge of interpreting IMF across different age groups, sexes and ethnicities. Overcoming these obstacles through consensus definitions, prospective multi‐ethnic research and the integration of advanced imaging with functional outcomes will be vital. If achieved, IMF could become a clinically important biomarker, complementing mass and strength‐based measures to guide treatments, assess risk and track muscle health throughout life.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"408 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149085970","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":"Aberrant Myelopoiesis and Haematopoietic Stem Cell Niche Remodelling Precedes Cancer Cachexia Onset in a Sex-Dependent Manner.","authors":"Alice Tate, Alex Brown, Lisa Ek Orloff, James Vanhie, Nicolas Collao, Cooper Brabrook, Victoria Moghadam, Vedrana Rajaković, Nadine Wiper-Bergeron, Michael De Lisio","doi":"10.1002/jcsm.70403","DOIUrl":"10.1002/jcsm.70403","url":null,"abstract":"<p><strong>Background: </strong>Male cancer patients are 30% more likely to develop cachexia compared to females; however, the underlying aetiology remains unknown. Myelopoiesis induces inflammation in cancer cachexia, which contributes to muscle atrophy. Whether differences in myelopoiesis during cancer cachexia initiation contribute to sex-based differences in cachexia incidence remains unknown.</p><p><strong>Methods: </strong>Male and female C57BL/6 and B6(C)-Ccr2^tm1.1Cln/J mice were randomized into sham (PBS) or were inoculated subcutaneously with Lewis lung carcinoma (LLC) to induce cachexia. Mice were sacrificed 2 (14 days), 2.5 (17 days) and 3.5 weeks (24 days) post-inoculation. Changes in body composition, haematopoietic stem and progenitor cells (HSPCs), myeloid immune cell migration, bone marrow niche cellular dynamics and CCL2 expression were assessed.</p><p><strong>Results: </strong>LLC inoculation reduced tumour-free body weight, lean mass, gastrocnemius-soleus mass and myofiber cross-sectional area (CSA) in males at 3.5 weeks (p < 0.05), while females maintained tumour-free body weight, lean mass and CSA. Within the bone marrow, haematopoietic stem cells (HSCs) were increased at 2, 2.5 and 3.5 weeks compared to sham in males and at 2.5 weeks compared to 2 and 3.5 weeks in females (p < 0.05). Multipotent progenitors (MPPs) were significantly increased at 2, 2.5 and 3.5 weeks compared to sham in males and at 2.5 weeks compared to sham, 2 and 3.5 weeks in females (p < 0.05). Downstream, common myeloid progenitors (CMPs) and granulocyte-monocyte progenitors (GMPs) were elevated in males at 2.5 weeks, with CCR2⁺GMPs peaking at 2.5 weeks in males and 3.5 weeks in females (p < 0.05). Sex differences in HSC niche composition were also observed with osteoprogenitors, osteoblasts and endothelial cells increased at 2 weeks in males, while females showed increased osteoprogenitors and endothelial progenitors at 2.5 weeks in tumour-bearing mice (p < 0.05). Plasma C-C motif chemokine ligand 2 (CCL2) concentrations increased with tumour progression in both sexes; however, CCR2⁺-progenitors and macrophages were decreased at 2.5 and 3.5 weeks compared to 2 weeks (p < 0.05). In skeletal muscle, CCL2 concentration increased at 3.5 weeks, and the proportion of CCR2⁺/CD206^- macrophages increased, while total macrophage abundance remained unchanged (p < 0.05). Macrophage subpopulations were related to decreasing CSA in males but not females.</p><p><strong>Conclusion: </strong>Our study suggests that aberrant myelopoiesis and sex-specific HSC niche remodelling precede muscle atrophy during cachexia development in males. These findings provide an important first step in understanding the role aberrant myelopoiesis plays in cancer cachexia and establish myeloid skewing as a potential therapeutic target.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 5","pages":"e70403"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190100","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":"Chemotherapy‐Induced Skeletal Muscle Dysfunction and Cognitive Impairment: A Muscle‐Brain Mechanistic Framework With Implications for Exercise Oncology","authors":"SoYoung Ahn,Jin‐Soo Kim,Daniel A. Galvao,Dennis R. Taaffe,Dong Hyun Yoon,Carolyn McIntyre,Christelle Schofield,Yoon Jung Chang,Jihee Min,Wook Song,Robert U. Newton","doi":"10.1002/jcsm.70394","DOIUrl":"https://doi.org/10.1002/jcsm.70394","url":null,"abstract":"ABSTRACT Chemotherapy commonly induces skeletal muscle dysfunction and cognitive impairment, complications that reduce treatment tolerance and quality of life. Skeletal muscle mass frequently declines during chemotherapy, with cohort studies reporting losses of 3%–10% across treatment courses, while chemotherapy‐induced cognitive impairment affects up to one‐third of patients. Emerging evidence indicates that chemotherapeutic agents impair mitochondrial function in peripheral tissues, including skeletal muscle, increasing systemic oxidative stress and inflammatory cytokines. These factors may promote oxidative stress and inflammation within the brain, particularly in the hippocampus, contributing to neuronal mitochondrial dysfunction, apoptosis and cognitive decline. Skeletal muscle may therefore represent an important component within a broader muscle–brain axis linking chemotherapy‐induced metabolic dysfunction with brain health. Targeted exercise improves skeletal muscle mitochondrial function, reduces systemic inflammation and oxidative stress and modulates multiple exercise‐responsive signalling pathways, including myokines such as brain‐derived neurotrophic factor and irisin. Collectively, these adaptations may contribute to improved neuronal health, neurogenesis and cognitive function. Understanding these interconnected mechanisms may inform exercise strategies to mitigate chemotherapy‐related cognitive impairment.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"58 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Overlap of Malnutrition, Sarcopenia and Related Nutritional Syndromes in a Large Haemodialysis Population.","authors":"Hanaa Noor, Subhashini Ganesan, Flavia Martinez Cantarutti, Ali Alharbi, Imed Helal, Joanne Reid, Adrian Slee","doi":"10.1002/jcsm.70386","DOIUrl":"10.1002/jcsm.70386","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease is a major global health burden linked to malnutrition, sarcopenia and related nutritional syndromes including protein-energy wasting (PEW)/cachexia and sarcopenic obesity (SO). Data from end-stage kidney disease (ESKD) populations in Saudi Arabia and the wider Middle East are scarce. This study assessed the prevalence and factors associated with malnutrition and sarcopenia risk in a large haemodialysis (HD) cohort and the co-occurrence of PEW/cachexia risk and SO.</p><p><strong>Methods: </strong>Multicentre, cross-sectional study in 40 dialysis clinics across Saudi Arabia (June-August 2024). Adults on maintenance HD ≥ 90 days were screened using the malnutrition-inflammation score (MIS; high risk > 5), SARC-F (sarcopenia risk ≥ 4) high risk, calf circumference (CC; cut-offs ≤ 34-cm males, ≤ 33-cm females), CC adjusted for body mass index (BMI) and oedema (Adj. CC) and SARC-CalF (sarcopenia risk ≥ 11). SO was defined as sarcopenia risk by SARC-CalF (Adj. CC) plus BMI > 30 kg/m². Routine blood chemistry (e.g., total iron-binding capacity [TIBC] and albumin) and screening tools were collected for physical function (Karnofsky), falls risk (Morse fall) and comorbidity (Charlson index). Univariate and multivariate logistic regression (adjusted for age, sex, diabetes, dialysis vintage and Kt/V) identified factors associated with each outcome.</p><p><strong>Results: </strong>Of 3722 HD patients (56.8% male; age 53.6 ± 15.8 years; BMI 26.8 ± 6.4 kg/m²), 48% had diabetes and 35% had high/very high Charlson comorbidity index. High nutritional risk (MIS > 5) was found in 44.5% (n = 1657) and sarcopenia risk (SARC-CalF [Adj. CC]) in 53.1% (n = 1978); 31.6% (n = 1175) had combined malnutrition and sarcopenia (M + S) and 7.7% (n = 285) had SO. Versus the no-risk group, M + S patients had lower albumin, TIBC, Karnofsky score and higher comorbidity index and Morse fall risk score (all p < 0.001). Independent factors associated with high nutritional risk included lower BMI, higher Charlson index, longer dialysis vintage, lower serum creatinine and higher triglycerides (all p < 0.05). Shared independent factors for sarcopenia risk were older age, higher comorbidity index, longer dialysis duration, lower creatinine and higher triglycerides (all p < 0.05).</p><p><strong>Conclusions: </strong>This is the first large-scale study to fully characterise a Saudi and Middle Eastern HD cohort. There was a very high risk of malnutrition and sarcopenia. Furthermore, a high number had both conditions and overlapping features of PEW/cachexia, which included high comorbidity and disability risk. Findings support routine, multitool nutritional and muscle screening in HD care, including younger patients.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 5","pages":"e70386"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072908","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":"Fibro-Adipogenic Progenitor Ablation Triggers Muscle Atrophy Through Cell Death-Induced Inflammation.","authors":"Yangyi E Luo, Young Il Lee, Zoe Abe-Teh, Rachel Y Young, Lan Wei-LaPierre, Elisabeth R Barton","doi":"10.1002/jcsm.70393","DOIUrl":"10.1002/jcsm.70393","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Skeletal muscle mass maintenance involves coordination of myofibers with mononuclear cell populations, including satellite cells, resident macrophages and fibro-adipogenic progenitors (FAPs). FAPs, identified by surface expression of PDGFRα, are important contributors to muscle homeostasis, as genetic ablation of FAPs induces rapid muscle atrophy. However, mechanisms underlying this response remain poorly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We utilized tamoxifen-inducible FAP specific diptheria toxin (DTA) mice (Pdgfra&lt;sup&gt;Cre-ERT2/+;&lt;/sup&gt; Rosa26&lt;sup&gt;^DTA/+&lt;/sup&gt;) to evaluate consequences of FAP deletion, measuring body and muscle mass, and isolated function on the extensor digitorum longus (EDL) and soleus (SOL). Neuromuscular junction (NMJ) patency was assessed via whole-mount staining, nerve vs. direct muscle stimulated function, and denervation-responsive expression targeting AchRα/β/γ. Immunofluorescence of muscle sections was used to investigate cellular and morphological changes. RT-qPCR measured expression of atrogenes, inflammatory chemokines/cytokines, and growth factors in tibialis anterior (TA) muscles. To modulate the immune response, mice were subjected to immune cell depletion, pharmacological Cxcr2 inhibition, or treatment with the anti-inflammatory steroid Vamorolone (VBP15).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Following tamoxifen administration, FAP density decreased 90%, coupled with a 30% loss of lean mass (p &lt; 0.001). Isolated contractile measurements showed that FAP-deleted muscles exhibited 25% reductions in maximal tetanic force in the EDL and SOL, while specific force and vulnerability to contractile damage remained unchanged. Whole-mount staining revealed preserved NMJ structural integrity, and functional testing showed no differences between nerve and direct muscle stimulation. RT-qPCR showed no change in genes encoding AchR subunits. Longitudinal body composition tracking revealed that FAP-deletion-induced muscle and fat loss occurred during tamoxifen administration and coincided with a 10-fold increase in the infiltration of macrophages and neutrophils. Robust 10- to 150-fold increases (p &lt; 0.0001) in chemokine transcript levels was observed soon after FAP deletion but preceded atrogene upregulation (Trim63, Fbxo32, Sqstm1, Ulk1). Ccl2 increased ~80-fold, Ccl12 ~ 80-fold, Cxcl1 ~ 50-fold, and Cxcl2 ~ 50-fold. While immune cell depletion exacerbated muscle atrophy by worsening mass loss and further increasing atrogene expression 5-fold, Cxcr2 inhibition or VBP15 treatment restored muscle mass by 15% (p &lt; 0.01). VBP15 treatment also resulted in a 50% reduction in atrogene expression and a 70% reduction in Cxcl1/2 expression levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our findings demonstrate that FAP deletion results in simple muscle atrophy without affecting muscular contractile properties and NMJ function. The atrophy induced by the loss of FAPs occurs through an inflammation-media","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 5","pages":"e70393"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079065","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 Skeletal Muscle Index Predicts Neoadjuvant Immunochemotherapy Tolerance and Survival in Oesophageal Squamous Cell Carcinoma","authors":"Yizhou Huang, Maohui Chen, Zhenyuan Yang, Bingqiang Cai, Yongcong Zhang, Hongjin Wang, Shuliang Zhang, Taidui Zeng, Chun Chen, Bin Zheng","doi":"10.1002/jcsm.70392","DOIUrl":"https://doi.org/10.1002/jcsm.70392","url":null,"abstract":"Background Low skeletal muscle index (SMI) may identify host vulnerability in patients receiving intensive cancer therapy. However, its association with treatment tolerance and outcomes during neoadjuvant immunochemotherapy (nICT) for oesophageal squamous cell carcinoma (OSCC) remains unclear. Methods This multicentre retrospective cohort included 461 patients with locally advanced OSCC who initiated nICT between 2020 and 2023; 404 underwent oesophagectomy. Pretreatment SMI at the third lumbar vertebra was measured by two blinded radiologists. Low SMI was defined using sex‐specific outcome‐derived cutoffs, with sensitivity analyses using published thresholds. Neoadjuvant treatment tolerance grade (NAT‐TG) was used as a composite measure of treatment tolerance and feasibility, integrating treatment modification and failure to undergo curative surgery. Results Among 461 patients (mean age, 61.2 ± 7.3 years; 21.3% female), low SMI was present in 121 (26.2%) and was independently associated with an unfavourable NAT‐TG composite (NAT‐TG2–3 vs. NAT‐TG1; adjusted OR, 2.48; 95% CI, 1.62–3.82; <jats:italic>p</jats:italic> &lt; 0.001). The association persisted after excluding six progression‐related surgical omissions (adjusted OR, 2.51; 95% CI, 1.59–3.95; <jats:italic>p</jats:italic> &lt; 0.001). The overall distribution of treatment‐related adverse event severity differed between groups ( <jats:italic>p</jats:italic> = 0.012), with grade ≥ 3 events occurring in 36.4% of patients with low SMI and 22.9% of those without low SMI. In the surgical population, low SMI was independently associated with severe postoperative complications (adjusted OR, 2.92; 95% CI, 1.51–5.63; <jats:italic>p</jats:italic> = 0.001). During a median follow‐up of 43 months, 165 deaths occurred. The 1‐year mortality rate in the intention‐to‐treat population was 8.5% (95% CI, 5.9%–11.0%). In the primary intention‐to‐treat model, low SMI was associated with poorer overall survival (adjusted HR, 2.36; 95% CI, 1.67–3.33; <jats:italic>p</jats:italic> &lt; 0.001). Associations were also observed for surgical overall survival (adjusted HR, 1.91; 95% CI, 1.31–2.80) and disease‐free survival (adjusted HR, 1.57; 95% CI, 1.11–2.22). Results were generally consistent when published SMI thresholds were applied. Conclusions Pretreatment low SMI was associated with less favourable nICT tolerance and feasibility, a higher incidence of severe postoperative complications and poorer survival. CT‐derived skeletal muscle assessment may complement baseline risk stratification, while intervention strategies require prospective validation.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"318 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149085944","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":"Early Identification and Prognostic Stratification of Cancer Cachexia Using Explainable Machine Learning: A Multicentre Cohort Study","authors":"Wei Huang, Kan Pan, Mingjian Zhao, Tingting Zhao, Nuo Xu, Hanping Shi","doi":"10.1002/jcsm.70370","DOIUrl":"https://doi.org/10.1002/jcsm.70370","url":null,"abstract":"Background Cancer cachexia is a heterogeneous syndrome that remains frequently underrecognized in routine oncology care, especially before overt wasting develops. We aimed to develop and externally validate an explainable two‐stage machine learning framework for early cachexia identification and prognostic stratification using routinely available clinical data. Methods In this multicentre real‐world study based on the INSCOC registry, 10 796 hospitalized adults with cancer were analysed, including 3995 patients with cachexia and 6801 without cachexia. First‐stage machine learning models were trained separately in high‐ and low‐prevalence settings to identify cachexia. Second‐stage survival models were developed in 1711 cachexia patients with follow‐up data from a 5172‐patient follow‐up cohort. A total of 586 deaths were observed in the cachexia follow‐up cohort. External validation used an independent Fujian cohort of 886 patients. Results Cachexia prevalence was 37.0% (3995/10 796). Compared with non‐cachexia patients, cachexia patients had lower median BMI (21.0 vs. 23.4 kg/m2), albumin (37.9 vs. 39.7 g/L), triceps skinfold thickness (13.0 vs. 16.0 mm), calf circumference (33.0 vs. 35.0 cm) and higher CRP (5.9 vs. 3.9 mg/L); all <jats:italic>p</jats:italic> &lt; 0.001. For cachexia identification, XGBoost achieved the best discrimination, with an AUC of 0.867 (95% CI: 0.857–0.878), sensitivity 0.706 and specificity 0.846 in the high‐prevalence group, and an AUC of 0.870 (95% CI: 0.861–0.880), sensitivity 0.817 and specificity 0.756 in the low‐prevalence group. In external validation, the AUCs were 0.744 in the high‐prevalence subgroup and 0.694 in the low‐prevalence subgroup. Among cachexia patients with follow‐up, the 1‐year mortality rate was 20.8% (95% CI: 19.0%–22.9%). For prognostic stratification, the random survival forest model showed the most favourable overall performance, with a C‐index of 0.680 and time‐dependent AUCs of 0.800, 0.777, 0.741 and 0.716 at 3, 6, 9 and 12 months, respectively. Advanced TNM stage and higher CRP were associated with worse survival, whereas higher albumin, prealbumin and HDL were associated with better survival. Conclusions This explainable two‐stage framework enables accurate cachexia identification across different prevalence settings and clinically meaningful prognostic stratification in patients with established cachexia. Using routine variables and independent external validation, it provides a practical basis for earlier recognition, risk‐adapted supportive care and precision management in oncology practice.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768566","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":"Cachexia vs. Obesity: A Persisting Imbalance Between Clinical Need and Research Effort","authors":"Carolyn Blair, Alexander P. Maxwell, Adrian Slee, Clare McKeaveney, Marion Carson, Faizan Awan, Malcolm Brown, Marissa Burgermaster, Andrew Davenport, Damian Fogarty, Denis Fouque, Oonagh Gooding, Kamyar Kalantar‐Zadeh, Karen Magee, Robert Mullan, Helen Noble, Sam Porter, David S. Seres, Joanne Shields, Ian Swaine, Miles Witham, Joanne Reid","doi":"10.1002/jcsm.70372","DOIUrl":"https://doi.org/10.1002/jcsm.70372","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"67 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768511","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":"Blood Biomarkers of Alzheimer's Disease and Gait Speed Trajectories in Community‐Dwelling Older Adults: A Cohort Study","authors":"Javier Leal‐Martín, Giulia Grande, Caterina Gregorio, Amaia Calderón‐Larrañaga, Alice Margherita Ornago, Laura Fratiglioni, Martina Valletta, Claudia Fredolini, Anna‐Karin Welmer, Bengt Winblad, Davide Liborio Vetrano","doi":"10.1002/jcsm.70365","DOIUrl":"https://doi.org/10.1002/jcsm.70365","url":null,"abstract":"Background Gait speed (GS) has been suggested as a predictor of incident dementia in old age. However, the mechanisms underlying this body–mind connection remain unclear, and it is still unknown whether trajectories of GS decline differ according to levels of blood biomarkers related to Alzheimer's disease ( <jats:sc>AD</jats:sc> ). This study aims to investigate the association between levels of seven blood biomarkers related to AD and long‐term GS changes in dementia‐free older adults living in the community. Methods The present study included 1665 community‐dwelling adults ≥ 60 years, followed for 15 years, drawn from the Swedish National study on Aging and Care in Kungsholmen (SNAC‐K). GS (m·s <jats:sup>−1</jats:sup> ) was assessed at baseline and at five subsequent follow‐up time points. Blood biomarkers, including serum amyloid‐ <jats:italic>β</jats:italic> 42 to amyloid‐ <jats:italic>β</jats:italic> 40 ratio (A <jats:italic>β</jats:italic> 42/40), phosphorylated Tau181 ( <jats:italic>p</jats:italic> ‐Tau181) and Tau217 ( <jats:italic>p</jats:italic> ‐Tau217), total Tau ( <jats:italic>t</jats:italic> ‐Tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), were collected from peripheral venous blood samples at baseline. Linear mixed‐effects models were implemented to investigate the association between blood biomarkers and GS changes over time. Results After adjusting for potential confounders, participants in the highest quartile of <jats:italic>p</jats:italic> ‐Tau181 (Model I; 4th quartile <jats:italic>β</jats:italic> : −0.008, 95% CI: −0.013; −0.003), <jats:italic>p</jats:italic> ‐Tau217 (Model I; 4th quartile <jats:italic>β</jats:italic> : −0.010, 95% CI: −0.015; −0.005), NfL (Model I; 4th quartile <jats:italic>β</jats:italic> : −0.013, 95% CI: −0.019; −0.006) and GFAP (Model I; 4th quartile <jats:italic>β</jats:italic> : −0.007, 95% CI: −0.013; −0.002) exhibited a steeper decline in GS over time, as compared with those in the lowest quartile. Notably, participants in these highest quartiles developed mobility limitations (GS &lt; 0.8 m·s <jats:sup>−1</jats:sup> ), on average, 2.3 to 6.0 years earlier. Of note, only the association between NfL and GS changes over time persisted after further adjusting for time‐varying global cognition. Conclusions Higher blood biomarker levels of AD are associated with accelerated trajectories of GS decline and earlier onset of mobility limitations. Consequently, a faster decline in GS may reflect underlying neurodegeneration and indicate changes in brain health.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"70 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768800","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":"Intermuscular Adipose Tissue as a Multimodality Quantitative Imaging Biomarker: Evidence Across Metabolic, Cardiovascular and Oncologic Diseases","authors":"Feier Ding, Atsushi Nakamoto, Xiaohan Zheng, Toru Honda, Gongzheng Wang, Yuwei Liu, Hideyuki Fukui, Takashi Ota, Masahiro Yanagawa, Noriyuki Tomiyama","doi":"10.1002/jcsm.70366","DOIUrl":"https://doi.org/10.1002/jcsm.70366","url":null,"abstract":"Intermuscular adipose tissue (IMAT) refers to adipose tissue located between muscle groups or beneath the muscle fascia, and its accumulation is closely linked to impaired muscle quality, reduced contractile function, and adverse metabolic profiles, establishing it as a core component of myosteatosis. Unlike subcutaneous and visceral adipose tissue, which reside outside the muscle architecture, IMAT expands within the muscle environment, where local metabolic and mechanical interactions may affect muscle integrity and performance. Elevated IMAT has been associated with diminished strength, impaired mobility, frailty, insulin resistance, and adverse cardiometabolic profiles, underscoring its clinical relevance beyond a passive fat depot. However, IMAT evidence remains dispersed across imaging techniques, anatomical regions, and disease‐specific literatures, limiting a unified understanding of its clinical utility. This review synthesizes current evidence on IMAT biology, imaging‐based quantification, disease‐specific distribution and clinical implications, with emphasis on its value as a risk‐stratification biomarker. Recent advances in medical imaging, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound and positron emission tomography (PET), have enabled noninvasive and reproducible IMAT quantification. These modalities provide complementary measures of muscle fat infiltration, including CT‐derived area, volume and attenuation; MRI‐based segmentation and proton density fat fraction; ultrasound echo intensity; and PET‐derived metabolic activity. Deep learning–based segmentation methods have improved large‐scale IMAT quantification and reproducibility across anatomical regions. Mechanistically, IMAT is associated with chronic low‐grade inflammation and impaired glucose homeostasis, promoting progressive fat infiltration and muscle degeneration. Human studies indicate that IMAT exhibits an inflammatory secretory profile linked to insulin resistance and metabolic dysfunction. Quantitative imaging shows anatomically heterogeneous IMAT distribution, with frequent involvement of the lower extremities, paraspinal muscles and trunk. Across disease settings, IMAT appears to provide complementary information beyond muscle mass alone by capturing muscle quality and systemic vulnerability. Evidence is strongest in oncology, where elevated IMAT or IMAT‐based ratios have repeatedly been associated with poorer survival, recurrence, treatment toxicity, and reduced treatment tolerance. In metabolic and musculoskeletal disorders, IMAT is consistently related to insulin resistance, reduced strength, impaired mobility, and frailty, whereas cardiovascular evidence suggests prognostic relevance but remains less standardized and more heterogeneous. Clinically, IMAT imaging may help identify patients whose preserved muscle size or body mass index masks poor muscle quality, thereby refining prognostic assessment, perioperative risk evaluation","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"21 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754448","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}