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Journal of Cachexia, Sarcopenia and Muscle最新文献

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Associations between indoor air pollution for cooking and heating with muscle and sarcopenia in Chinese older population 中国老年人烹饪和取暖的室内空气污染与肌肉和少肌症的关系。
IF 8.9 1区 医学 Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13281
Zhigang Hu, Yufeng Tian, Xinyu Song, Fanjun Zeng, Ailan Yang

Background

Exposure to air pollution brings the advent effect for various diseases, but study about the relationship between air pollution and ageing is scant. We aimed to determine the associations between household air pollution for cooking and heating with muscle and sarcopenia in Chinese older population by a nationally representative study.

Methods

This cross-sectional study included individuals aged 60 and above from the China Health and Retirement Longitudinal Study between 2011 and 2015. The diagnosis of sarcopenia was defined by low muscle mass with low muscle strength and/or reduced physical performance. Generalized additive analyses and dose-dependent analyses with three models were used to assess the effects of different pattern of cooking and heating on muscle and sarcopenia.

Results

A total of 8126 Chinese older individuals with predominant male (53.7%) and mean age of 67.3 ± 6.0 years were included in our study. Solid fuel use in cooking showed significant declines in muscle strength (β = −0.424, 95% CI: −0.767, −0.082, P = 0.01 in model 3) and mass (β = −0.034, 95% CI: −0.051, −0.017, P < 0.01 in model 3), when compared with clean fuel use in cooking, respectively. Solid fuel for heating was correlated with lower muscle strength (β = −0.637, 95% CI: −1.033, −0.241, P < 0.01 in model 3) than clean fuel for heating. The joint use of solid fuel for cooking and heating was associated with reduced muscle strength (β = −0.835, 95% CI: −1.306, −0.365, P < 0.01 in model 3) and mass (β = −0.038, 95% CI: −0.061, −0.015, P < 0.01 in model 3) than clean fuel for cooking and heating. Solid fuel for cooking was associated with significantly increased risk of low muscle strength (adjusted OR = 1.29, 95% CI: 1.11, 1.50, P < 0.01 in model 3) and mass (adjusted OR = 1.35, 95% CI: 1.11, 1.61, P < 0.01 in model 3), possible sarcopenia (adjusted OR = 1.33, 95% CI: 1.19, 1.48, P < 0.01 in model 3) and sarcopenia (adjusted OR = 1.44, 95% CI: 1.21, 1.72, P < 0.01 in model 3) compared with clean fuel for cooking. Solid fuel for heating had a significant correlation with low muscle strength (adjusted OR = 1.30, 95% CI: 1.09, 1.56, P < 0.01 in model 3) and possible sarcopenia (adjusted OR = 1.49, 95% CI: 1.31, 1.70, P < 0.01 in model 3). Dose-dependent manner was shown in the associations between the number of solid fuel with low muscle strength and possible sarcopenia. Clean fuel for cooking and solid fuel for heating was positively associated with t

背景:暴露在空气污染中会导致各种疾病的出现,但关于空气污染与衰老之间关系的研究很少。我们旨在通过一项具有全国代表性的研究,确定中国老年人烹饪和取暖的家庭空气污染与肌肉和少肌症之间的关系。方法:这项横断面研究纳入了2011年至2015年间中国健康与退休纵向研究中60岁及以上的个体。肌肉减少症的诊断是指肌肉质量低、肌肉力量低和/或体力下降。使用三个模型的广义加性分析和剂量依赖性分析来评估不同烹饪和加热模式对肌肉和少肌症的影响。结果:本研究共纳入8126名中国老年人,其中男性占53.7%,平均年龄67.3±6.0岁。烹饪中固体燃料的使用显示出肌肉力量(模型3中的β=-0.424,95%CI:-0.767,-0.082,P=0.01)和质量(β=-0.034,95%CI:-0.051,-0.017,P)的显著下降。
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引用次数: 2
Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease 对力量发展率的分析显示,患有慢性肾脏疾病的老年患者具有较高的神经肌肉疲劳能力。
IF 8.9 1区 医学 Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13280
Antoine Chatrenet, Giorgina Piccoli, Jean Michel Audebrand, Massimo Torreggiani, Julien Barbieux, Charly Vaillant, Baptiste Morel, Sylvain Durand, Bruno Beaune

Background

Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients.

Methods

Inclusion criteria for CKD patients were age ≥ 60 years old and glomerular filtration rate (GFR) < 45 mL/min/1.73 m2 not on dialysis, and those for controls were GFR > 60 mL/min/1.73 m2, age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD50, RFD75, RFD100, RFD150 and RFD200, respectively), peak RFD (RFDpeak in absolute; NRFDpeak normalized), time-to-peak RFD (t-RFDpeak) and the relative force at RFDpeak (MVF-RFDpeak). A statistical parametric mapping approach was performed on the force, impulse and RFD–time curves. The integrated sEMG with time at 0–30, 0–50, 0–100 and 0–200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex.

Results

The cohort of 159 individuals had a median age of 69 (9IQR) years and body mass index was 27.6 (6.2IQR) kg/m2. Propensity-score-matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFDpeak (P = 0.009; η2p = 0.034) and RFD75 and RFD100 (for both P < 0.001; η2p = 0.068 and 0.064). The one-dimensional analysis confirmed that CKD males manifest higher and delayed neuromuscular fatigability, especially before 100 ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0–100 ms (at rest: P = 0.049, Cohen's d = 0.458) and 0–200 ms (at rest: P = 0.016, Cohen's d = 0.496; during exercise: P = 0.006, Cohen's d = 

背景:慢性肾脏疾病(CKD)会导致肌肉萎缩和最大自主力(MVF)降低。对CKD患者的神经肌肉疲劳性知之甚少,其定义为运动过程中肌肉力量能力的降低。神经肌肉疲劳是日常生活中一个重要的生理参数。爆炸力的量化已被证明是评估神经肌肉疲劳能力的一种敏感手段。因此,我们的研究使用爆炸力估计来评估老年CKD患者的神经肌肉疲劳能力。方法:CKD患者的纳入标准为年龄≥60岁且肾小球滤过率(GFR)为2(未透析),对照组为GFR>60 mL/min/1.73 m2,年龄与糖尿病匹配。疲劳性方案侧重于抓握任务和表面肌电图(sEMG)。从力发展速率(RFD)中提取标量:绝对时间段和归一化时间段(分别为50、75、100、150和200ms、RFD50、RFD75、RFD100、RFD150和RFD200)、峰值RFD(RFDpeak为绝对值;NRFDpeak归一化)、达到峰值RFD的时间(t-RFDpeake)和RFD峰值处的相对力(MVF-RFDpeach)。对力、脉冲和RFD时间曲线进行了统计参数映射。提取相对于sEMG活性开始的0-30、0-50、0-100和0-200ms时间间隔的积分sEMG,并分别对每个性别的组进行比较。结果:159名患者的中位年龄为69岁(9IQR),体重指数为27.6(6.2IQR)kg/m2。倾向评分匹配组按性别平衡CKD患者和对照组,66名男性和34名女性。在标量分析中,CKD患者在收缩早期表现出比对照组更高的NRFDpeak下降率(P=0.009;η2p=0.034)、RFD75和RFD100(对于P2 P=0.068和0.064)。一维分析证实,CKD男性表现出更高和延迟的神经肌肉疲劳性,尤其是在收缩开始100 ms之前。CKD患者的sEMG在0-100毫秒(休息时:P=0.049,Cohen’s d=0.458)和0-200毫秒(静息时:P=0.016,Cohen‘s d=0.496;运动时:P=0.006,Cohen′s d=0.421)时间窗内低于对照组。对照组显示,在0-30ms(P=0.020,Cohen’s d=0.533)和0-50ms(P=0.010,Cohen‘s d=0.640)时间窗口内,sEMG的下降幅度大于CKD患者。与女性相反,男性在各组之间表现出几乎相同的差异。结论:我们的研究首次表明,CKD患者比对照组具有更高的疲劳性,这可能与运动单位募集受损有关,突出了CKD的神经驱动障碍。需要进一步的研究来证实这些发现。
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引用次数: 1
Faecal microbiota transplantation from young rats attenuates age-related sarcopenia revealed by multiomics analysis 多组学分析显示,幼鼠粪便微生物群移植可减轻与年龄相关的少肌症。
IF 8.9 1区 医学 Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13294
Xiaoxing Mo, Lihui Shen, Ruijie Cheng, Pei Wang, Lin Wen, Yunhong Sun, Qiang Wang, Juan Chen, Shan Lin, Yuxiao Liao, Wei Yang, Hong Yan, Liegang Liu

Background

Gut microbiota plays a key role in the development of sarcopenia via the ‘gut-muscle’ axis, and probiotics-based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age-related sarcopenia.

Methods

The fecal microbiota of either young (12 weeks) or old (88 weeks) donor rats was transplanted into aged recipient rats for 8 weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16 s rRNA, serum non-targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles.

Results

As evaluated by magnetic resonance imaging examination, grip strength test (P < 0.01), rotarod test (P < 0.05), and exhaustive running test (P < 0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age-related atrophy and poor regeneration capacity in fast- and slow-switch muscles, which were manifested by the decrease in slow-switch myofibres (both P < 0.01) and muscle interstitial fibrosis (both P < 0.05) and the increase in the cross-section area of myofibres (both P < 0.001), fast-switch myofibres (both P < 0.01), and muscle satellite cells (both P < 0.001). In addition, yFMT ameliorated age-related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites—Akkermansia, Lactococcus, Lactobacillus, γ-glutamyltyrosine, 3R-hydroxy-butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites—Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole-3-carboxilic acid-O-sulphate, and trimethylamine N-oxide. Also, yFMT prevented age-related destruction of gut barrier integrity by increasing the density of goblet cells (P < 0.0001) and the expression levels of mucin-2 (P < 0.0001) and tight junctional proteins (all P < 0.05). Meanwhile, yFMT attenuated age-related impairment of mitochondrial biogenesis and function in fast- and slow-switch muscles. Correlation analysis revealed that yFMT-i

背景:肠道微生物群通过“肠道肌肉”轴在少肌症的发展中发挥着关键作用,基于益生菌的治疗可能是少肌症患者的一种策略。年轻供体粪便微生物群移植(yFMT)因其益生菌功能而备受关注。然而,yFMT是否对老年受试者的少肌症有效在很大程度上是未知的。因此,我们旨在研究yFMT对年龄相关性少肌症的影响和机制。方法:将青年(12周)或老年(88周)供体大鼠的粪便微生物群移植到老年受体大鼠体内,持续8周。然后,测量肌肉质量、肌肉力量、肌肉功能、肌肉萎缩和肌肉再生能力。对粪便16s rRNA、血清非靶向代谢组、肠道屏障完整性和肌肉转录组进行分析,以阐明肠道微生物群和骨骼肌之间的相互作用。结果:磁共振成像检查、握力测试(P结论:yFMT可重塑肠道微生物群和代谢产物的微生态失调,维持肠道屏障完整性,改善肌肉线粒体功能障碍,最终缓解老年大鼠少肌症。
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引用次数: 1
Corylifol A ameliorates muscle atrophy by inhibiting TAOK1/p38-MAPK/FoxO3 pathway in cancer cachexia Corylifol A通过抑制癌症恶病质中TAOK1/p38-MAPK/FoxO3途径改善肌肉萎缩。
IF 8.9 1区 医学 Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13288
Ruiqin Zhang, Qiang Shen, Yueping Wang, Xue Deng, Jialing Fan, Xiaofan Gu, Meng Fan, Kun Wei, Chun-Ru Cheng, Wei-Dong Zhang, Xiong-wen Zhang, Xuan Liu

Background

Corylifol A (CYA) is one of the main active components of Psoralea corylifolia L. CYA had been reported to have ameliorating effects on dexamethasone-induced atrophy of C2C12 mouse skeletal myotubes, but its effects on cancer cachexia were unclear. Here, we checked the influence of CYA on muscle atrophy in cancer cachexia mice and tried to clarify its mechanisms.

Methods

C26 tumour-bearing mice were applied as the animal model to examine the effects of CYA in attenuating cachexia symptoms. The in vitro cell models of TNF-α-induced C2C12 myotubes or ad-mRFP-GFP-LC3B-transfected C2C12 myotubes were used to check the influence of CYA on myotube atrophy based on both ubiquitin proteasome system (UPS) and autophagy-lysosome system. The possible direct targets of CYA were searched using the biotin-streptavidin pull-down assay and then confirmed using the Microscale thermophoresis binding assay. The levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting and immunocytochemical assay.

Results

The administration of CYA prevented body weight loss and muscle wasting in C26 tumour-bearing mice without affecting tumour growth. At the end of the experiment, the body weight of mice treated with 30 mg/kg of CYA (23.59 ± 0.94 g) was significantly higher than that of the C26 model group (21.66 ± 0.56 g) with P < 0.05. The values of gastrocnemius muscle weight/body weight of mice treated with 15 or 30 mg/kg CYA (0.53 ± 0.02% and 0.54 ± 0.01%, respectively) were both significantly higher than that of the C26 model group (0.45 ± 0.01%) with P < 0.01. CYA decreased both UPS-mediated protein degradation and autophagy in muscle tissues of C26 tumour-bearing mice as well as in C2C12 myotubes treated with TNF-α. The thousand-and-one amino acid kinase 1 (TAOK1) was found to be the direct binding target of CYA. CYA inhibited the activation of TAOK1 and its downstream p38-MAPK pathway thus decreased the level and nuclear location of FoxO3. siRNA knockdown of TAOK1 or regulation of the p38-MAPK pathway using activator or inhibitor could affect the ameliorating effects of CYA on myotube atrophy.

Conclusions

CYA ameliorates cancer cachexia muscle atrophy by decreasing both UPS degradation and autophagy. The ameliorating effects of CYA on muscle atrophy might be based on its binding with TAOK1 and inhibiting the TAOK1/p38-MAPK/FoxO3 pathway.

背景:CorylifolA(CYA)是补骨脂的主要活性成分之一。据报道,它对地塞米松诱导的C2C12小鼠骨骼肌管萎缩有改善作用,但对癌症恶病质的影响尚不清楚。在此,我们检测了CYA对癌症恶病质小鼠肌肉萎缩的影响,并试图阐明其机制。方法:以C26荷瘤小鼠为动物模型,观察CYA对恶病质症状的减轻作用。基于泛素-蛋白酶体系统(UPS)和自噬-溶酶体系统,使用TNF-α诱导的C2C12肌管或ad-mRFP-GFP-LC3B转染的C2C12-肌管的体外细胞模型来检测CYA对肌管萎缩的影响。使用生物素-链霉亲和素下拉测定法搜索CYA的可能直接靶标,然后使用微型热泳结合测定法确认。在体外和体内实验中,使用蛋白质印迹和免疫细胞化学分析检测相关信号蛋白的水平。结果:CYA的给药在不影响肿瘤生长的情况下防止了C26荷瘤小鼠的体重减轻和肌肉萎缩。实验结束时,30 mg/kg CYA治疗的小鼠体重(23.59±0.94 g)显著高于C26模型组(21.66±0.56 g),P<0.01。结论:CYA通过减少UPS降解和自噬来改善癌症恶病质肌肉萎缩。CYA对肌肉萎缩的改善作用可能是基于其与TAOK1的结合和抑制TAOK1/p38 MAPK/FoxO3通路。
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引用次数: 0
A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis 牛骨骼肌的单细胞图谱揭示了调节肌内脂肪生成和纤维生成的机制。
IF 8.9 1区 医学 Pub Date : 2023-07-12 DOI: 10.1002/jcsm.13292
Leshan Wang, Peidong Gao, Chaoyang Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth McMillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Background

Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods

Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell–cell communication analysis, were performed to elucidate heterogeneities and differentiation processes of individual cell types and differences between cattle breeds. Experiments were conducted to validate the function and specificity of identified key regulatory and marker genes. Integrated analysis with multiple published human and non-human primate datasets was performed to identify common mechanisms.

Results

A total of 32 708 cells and 21 clusters were identified, including fibro/adipogenic progenitor (FAP) and other resident and infiltrating cell types. We identified an endomysial adipogenic FAP subpopulation enriched for COL4A1 and CFD (log2FC = 3.19 and 1.92, respectively; P < 0.0001) and a perimysial fibrogenic FAP subpopulation enriched for COL1A1 and POSTN (log2FC = 1.83 and 0.87, respectively; P < 0.0001), both of which were likely derived from an unspecified subpopulation. Further analysis revealed more progressed adipogenic programming of Wagyu FAPs and more advanced fibrogenic programming of Brahman FAPs. Mechanistically, NAB2 drives CFD expression, which in turn promotes adipogenesis. CFD expression in FAPs of young cattle before the onset of intramuscular adipogenesis was predictive of IMF contents in adulthood (R2 = 0.885, P < 0.01). Similar adipogenic and fibrogenic FAPs were identified in humans and monkeys. In aged humans with metabolic syndrome and progressed Duchenne muscular dystrophy (DMD) patients, increased CFD expression was observed (P < 0.05 and P < 0.0001, respectively), which was positively correlated with adipogenic marker expression, including ADIPOQ (R2 = 0.303, P < 0.01; and R2 = 0.348, P < 0.01, respectively). The specificity of

背景:肌内脂肪(IMF)和肌内结缔组织(IMC)经常出现在人类肌病中,是牛肉质量的核心。调节其积累的机制仍知之甚少。在这里,我们探索了使用肉牛作为肌肉内脂肪生成和纤维生成机制研究的新模型的可能性。方法:对和牛(高IMF)、婆罗门(IMC丰富但IMF稀少)和和牛/婆罗门杂交牛三个品种进行骨骼肌单细胞RNAseq检测。进行了复杂的生物信息学分析,包括聚类分析、基因集富集分析、基因调控网络构建、RNA速度、假时间分析和细胞-细胞通信分析,以阐明单个细胞类型的异质性和分化过程以及牛品种之间的差异。进行实验以验证已鉴定的关键调控基因和标记基因的功能和特异性。对多个已发表的人类和非人类灵长类动物数据集进行了综合分析,以确定共同的机制。结果:共鉴定出32708个细胞和21个簇,包括纤维/脂肪生成祖细胞(FAP)和其他驻留和浸润细胞类型。我们鉴定了富含COL4A1和CFD的肌内脂肪生成FAP亚群(log2FC分别为3.19和1.92;P 2=0.885,P 2=0.303,P 2=0.348,P结论:我们的研究证明了肉牛作为研究IMF和IMC的模型的可行性。我们说明了肌肉脂肪生成和纤维生成过程中的FAP编程,并揭示了CFD作为牛和人IMF积累的预测因子和生物标志物的可靠性。
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引用次数: 1
Explainable machine learning model for predicting skeletal muscle loss during surgery and adjuvant chemotherapy in ovarian cancer 可解释的机器学习模型用于预测卵巢癌症手术和辅助化疗期间骨骼肌损失。
IF 8.9 1区 医学 Pub Date : 2023-07-12 DOI: 10.1002/jcsm.13282
Wen-Han Hsu, Ai-Tung Ko, Chia-Sui Weng, Chih-Long Chang, Ya-Ting Jan, Jhen-Bin Lin, Hung-Ju Chien, Wan-Chun Lin, Fang-Ju Sun, Kun-Pin Wu, Jie Lee

Background

Skeletal muscle loss during treatment is associated with poor survival outcomes in patients with ovarian cancer. Although changes in muscle mass can be assessed on computed tomography (CT) scans, this labour-intensive process can impair its utility in clinical practice. This study aimed to develop a machine learning (ML) model to predict muscle loss based on clinical data and to interpret the ML model by applying SHapley Additive exPlanations (SHAP) method.

Methods

This study included the data of 617 patients with ovarian cancer who underwent primary debulking surgery and platinum-based chemotherapy at a tertiary centre between 2010 and 2019. The cohort data were split into training and test sets based on the treatment time. External validation was performed using 140 patients from a different tertiary centre. The skeletal muscle index (SMI) was measured from pre- and post-treatment CT scans, and a decrease in SMI ≥ 5% was defined as muscle loss. We evaluated five ML models to predict muscle loss, and their performance was determined using the area under the receiver operating characteristic curve (AUC) and F1 score. The features for analysis included demographic and disease-specific characteristics and relative changes in body mass index (BMI), albumin, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The SHAP method was applied to determine the importance of the features and interpret the ML models.

Results

The median (inter-quartile range) age of the cohort was 52 (46–59) years. After treatment, 204 patients (33.1%) experienced muscle loss in the training and test datasets, while 44 (31.4%) patients experienced muscle loss in the external validation dataset. Among the five evaluated ML models, the random forest model achieved the highest AUC (0.856, 95% confidence interval: 0.854–0.859) and F1 score (0.726, 95% confidence interval: 0.722–0.730). In the external validation, the random forest model outperformed all ML models with an AUC of 0.874 and an F1 score of 0.741. The results of the SHAP method showed that the albumin change, BMI change, malignant ascites, NLR change, and PLR change were the most important factors in muscle loss. At the patient level, SHAP force plots demonstrated insightful interpretation of our random forest model to predict muscle loss.

Conclusions

Explainable ML model was developed using clinical data to identify patients experiencing muscl

背景:癌症患者在治疗过程中骨骼肌丢失与生存率低有关。尽管可以通过计算机断层扫描(CT)来评估肌肉质量的变化,但这种劳动密集型的过程可能会削弱其在临床实践中的实用性。本研究旨在开发一种基于临床数据预测肌肉损失的机器学习(ML)模型,并通过应用SHapley加性预测(SHAP)方法来解释ML模型。方法:这项研究包括了617名癌症患者的数据,他们在2010年至2019年期间在一家三级中心接受了初级减瘤手术和基于铂的化疗。根据治疗时间将队列数据分为训练集和测试集。使用来自不同三级中心的140名患者进行外部验证。通过治疗前后的CT扫描测量骨骼肌指数(SMI),SMI下降≥5%被定义为肌肉损失。我们评估了五个ML模型来预测肌肉损失,并使用受试者工作特征曲线下面积(AUC)和F1评分来确定它们的性能。分析的特征包括人口统计学和疾病特异性特征以及体重指数(BMI)、白蛋白、中性粒细胞与淋巴细胞比率(NLR)和血小板与淋巴细胞比率的相对变化。应用SHAP方法来确定特征的重要性并解释ML模型。结果:队列的中位(四分位间距)年龄为52岁(46-59岁)。治疗后,204名患者(33.1%)在训练和测试数据集中出现肌肉损失,而44名患者(31.4%)在外部验证数据集中出现了肌肉损失。在五个评估的ML模型中,随机森林模型获得了最高的AUC(0.856,95%置信区间:0.854-0.859)和F1得分(0.726,95%可信区间:0.722-0.730)。在外部验证中,随机林模型的AUC为0.874,F1得分为0.741,优于所有ML模型。SHAP法的结果表明,白蛋白变化、BMI变化、恶性腹水、NLR变化和PLR变化是肌肉损失的最重要因素。在患者层面,SHAP力图展示了对我们的随机森林模型的深刻解释,以预测肌肉损失。结论:使用临床数据开发了可解释的ML模型,以识别治疗后出现肌肉损失的患者,并提供特征贡献的信息。使用SHAP方法,临床医生可以更好地了解肌肉损失的原因,并针对性地采取干预措施来抵消肌肉损失。
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引用次数: 0
Comment on ‘Prediabetes is an independent risk factor for sarcopenia in older men, but not in older women: the Bunkyo Health Study’ by Kaga et al. Kaga等人对“糖尿病前期是老年男性少肌症的独立危险因素,但不是老年女性:Bunkyo健康研究”的评论。
IF 8.9 1区 医学 Pub Date : 2023-07-12 DOI: 10.1002/jcsm.13293
Shanhu Qiu, Xue Cai, Zilin Sun, Tongzhi Wu

We read, with great interest, the recent article by Kaga et al., in which prediabetes was reported to be associated with sarcopenia in older men but not in older women based on the cross-sectional analysis using the baseline data from the Bunkyo Health Study.1 This finding indicates that sarcopenia could have occurred prior to the onset of diabetes, particularly in older men, and highlights the need of conducting screening-oriented strategy for sarcopenia prevention in the aging population. However, in this article, several issues are worthy of discussion.

First, as indicated in the Methods part, the authors performed separate analyses by sex for the association of glycaemic status with sarcopenia. They found that after multivariate adjustment, prediabetes was associated with higher odds for sarcopenia compared with normoglycaemia (odds ratio [OR] 2.08, 95% confidence interval [CI]: 1.03 to 4.20) in men but not in women (OR 1.04, 95% CI: 0.61 to 1.76). However, when combining older men and women together, results from the fixed meta-analytical approach showed that prediabetes might not be significantly associated with higher odds of sarcopenia (OR 1.33, 95% CI: 0.87 to 2.03, P for heterogeneity = 0.12). Moreover, the interaction effect between men and women was not significant (P = 0.12), based on the test for interaction,2 suggesting that sex may not mediate the association of prediabetes with sarcopenia. A possible explanation for this inconsistent outcome between men and women, as shown by Kaga et al.,1 might be attributable to the difference in the sample sizes of male and female participants and hence the statistical power. However, as already noted by the authors in their Methods part that there existed considerable differences in body composition, muscle strength, or physical function in the aging population, it is therefore appropriate and reasonable to perform sex-stratified analyses. As a result, future studies with larger sample sizes are required to confirm the present findings regarding the association of prediabetes with sarcopenia between sex in the aging population.

Second, employing oral glucose tolerance test and haemoglobin A1c (HbA1c) to ascertain prediabetes diagnostic criteria by the Japan Diabetes Society is a strength of this article. However, there exists controversies regarding the cut-off points of fasting blood glucose and HbA1c for defining prediabetes. For example, the American Diabetes Association recommends a fasting blood glucose at 5.6–6.9 mmol/L to diagnose prediabetes, while the World Health Organization suggests 6.1–6.9 mmol/L; the American Diabetes Association recommends a HbA1c at 5.7–6.4% (39–47 mmol/mol) to diagnose prediabetes, while the International Expert Committee advocates 6.0–6.4% (42–47 mmol/mol).3 It is therefore of interest to know whether the study outcomes a

我们阅读,怀着极大的兴趣,最近的文章Kaga et al .,前驱糖尿病的报道与sarcopenia在老年男性而不是基于横断面分析老年妇女使用基线数据Bunkyo卫生Study.1这个发现表明sarcopenia可能发生糖尿病的发病之前,尤其是老年男性,凸显了需要进行screening-oriented老龄化sarcopenia预防策略。然而,在本文中,有几个问题值得讨论。首先,如方法部分所述,作者按性别分别分析了血糖状态与肌肉减少症的关系。他们发现,在多因素调整后,与血糖正常者相比,糖尿病前期男性发生肌肉减少症的几率更高(比值比[OR] 2.08, 95%可信区间[CI]: 1.03至4.20),而女性没有(比值比[OR] 1.04, 95%可信区间[CI]: 0.61至1.76)。然而,当将老年男性和女性结合在一起时,固定荟萃分析方法的结果显示,前驱糖尿病可能与肌肉减少症的高几率没有显著相关性(OR 1.33, 95% CI: 0.87至2.03,P为异质性= 0.12)。此外,根据相互作用的检验,男性和女性之间的相互作用效应不显著(P = 0.12), 2表明性别可能不会介导糖尿病前期与肌肉减少症的关联。正如Kaga等人所表明的,男性和女性之间结果不一致的一个可能的解释是,男性和女性参与者的样本量不同,因此统计能力不同。然而,正如作者在他们的方法部分已经指出的那样,老龄人口在身体组成、肌肉力量或身体功能方面存在相当大的差异,因此进行性别分层分析是适当和合理的。因此,未来需要更大样本量的研究来证实目前的研究结果,即糖尿病前期与老年人群中性别之间肌肉减少症的关系。其次,日本糖尿病学会采用口服糖耐量试验和血红蛋白A1c (HbA1c)确定糖尿病前期诊断标准是本文的优势。然而,对于空腹血糖和糖化血红蛋白的临界值定义前驱糖尿病存在争议。例如,美国糖尿病协会建议空腹血糖在5.6-6.9 mmol/L来诊断前驱糖尿病,而世界卫生组织建议为6.1-6.9 mmol/L;美国糖尿病协会推荐HbA1c在5.7-6.4% (39-47 mmol/mol)诊断前驱糖尿病,而国际专家委员会推荐6.0-6.4% (42-47 mmol/mol)因此,了解研究结果是否受到不同的前驱糖尿病诊断标准的影响是很有意义的。第三,根据空腹血糖和2小时血糖,可以将前驱糖尿病分为不同的表型,包括分离性空腹血糖受损(IFG),分离性糖耐量受损(IGT),或两者兼而有之。虽然人们普遍认为IFG和IGT都表现出胰岛素抵抗和β细胞功能障碍,但它们在潜在的病理生理上存在很大差异,并且代谢异常也有明显不同例如,IFG的特征是严重的肝脏胰岛素抵抗,但没有明确的证据表明骨骼肌(外周)胰岛素敏感性受损,而IGT的特征是明显的骨骼肌胰岛素抵抗,但只有中度的肝脏胰岛素抵抗。鉴于这些,并考虑到以生活方式为基础的2型糖尿病预防的益处可能受到糖尿病前期表型的影响,因此进一步研究糖尿病前期表型与肌肉减少症的关系是很有趣的。最后,前驱糖尿病是一种中间血糖状态,在自然史中可发展为糖尿病,维持为前驱糖尿病,或退化为正常血糖。先前的研究表明,前驱糖尿病的进展可能会增加心血管疾病的风险和全因死亡率,而前驱糖尿病的消退可能会带来健康益处,包括降低糖尿病或心血管疾病的风险虽然本研究的横断面设计可能无法解决糖尿病前期状态改变是否会影响肌少症的发展,但未来采用前瞻性队列设计的研究可能会受益于关注这一问题,因为它可能为实施有效的预防老年糖尿病前期人群肌少症的方法提供一些线索。作者声明他们没有利益冲突。
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引用次数: 0
Prognostic impact of cachexia by multi-assessment in older adults with heart failure: FRAGILE-HF cohort study 多重评估对老年心力衰竭患者恶病质预后的影响:FRAGILE-HF队列研究。
IF 8.9 1区 医学 Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13291
Emi Maekawa, Takumi Noda, Daichi Maeda, Masashi Yamashita, Shota Uchida, Nobuaki Hamazaki, Kohei Nozaki, Hiroshi Saito, Kazuya Saito, Yuki Ogasahara, Masaaki Konishi, Takeshi Kitai, Kentaro Iwata, Kentaro Jujo, Hiroshi Wada, Takatoshi Kasai, Hirofumi Nagamatsu, Tetsuya Ozawa, Katsuya Izawa, Shuhei Yamamoto, Naoki Aizawa, Ryusuke Yonezawa, Kazuhiro Oka, Junya Ako, Shin-ichi Momomura, Nobuyuki Kagiyama, Yuya Matsue, Kentaro Kamiya

Background

Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple assessments, with the prognosis of HF in older adults.

Methods

This study is a secondary analysis of the data from the FRAGILE-HF study, a prospective multicentre cohort study that enrolled consecutive hospitalized patients aged ≥65 years with HF. Patients were divided into two groups: the cachexia and non-cachexia groups. Cachexia was defined according to Evans's criteria by assessing weight loss, muscle weakness, fatigue, anorexia, a decreased fat-free mass index and an abnormal biochemical profile. The primary outcome was all-cause mortality, as assessed in the survival analysis.

Results

Cachexia was present in 35.5% of the 1306 enrolled patients (median age [inter-quartile range], 81 [74–86] years; 57.0% male); 59.6%, 73.2%, 15.6%, 71.0%, 44.9% and 64.6% had weight loss, decreased muscle strength, a low fat-free mass index, abnormal biochemistry, anorexia and fatigue, respectively. All-cause mortality occurred in 270 patients (21.0%) over 2 years. The cachexia group (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.173–1.903; P = 0.001) had a higher mortality risk than the non-cachexia group after adjusting for the severity of HF. Cardiovascular and non-cardiovascular deaths occurred in 148 (11.3%) and 122 patients (9.3%), respectively. The adjusted HRs for cachexia in cardiovascular mortality and non-cardiovascular mortality were 1.456 (95% CI, 1.048–2.023; P = 0.025) and 1.561 (95% CI, 1.086–2.243; P = 0.017), respectively. Among the cachexia diagnostic criteria, decreased muscle strength (HR, 1.514; 95% CI, 1.095–2.093; P = 0.012) and low fat-free mass index (HR, 1.424; 95% CI, 1.052–1.926; P = 0.022) were significantly associated with high all-cause mortality, but there was no significant association between weight loss alone (HR, 1.147; 95% CI, 0.895–1.471; P = 0.277) and all-cause mortality.

Conclusions

Cachexia evaluated by multi-assessment was present in one third of older adults with HF and was associated with a worse prognosis. A multimodal assessment of cachexia may be helpful for risk stratification in older patients with HF.

背景:恶病质严重影响心力衰竭(HF)患者的预后;然而,目前尚无标准的恶病质诊断方法。本研究旨在调查Evans标准(包括多项评估)与老年人HF预后的关系。方法:本研究是对FRAGILE-HF研究数据的二次分析,FRAGILE-HF研究是一项前瞻性多中心队列研究,纳入了年龄≥65岁的HF连续住院患者。患者分为两组:恶病质组和非恶病质对照组。根据Evans的标准,通过评估体重减轻、肌肉无力、疲劳、厌食、无脂肪质量指数下降和异常生化特征来定义恶病质。主要结果是生存分析中评估的全因死亡率。结果:1306名入选患者中有35.5%存在恶病质(中位年龄[四分位间距],81[74-86]岁;57.0%为男性);59.6%、73.2%、15.6%、71.0%、44.9%和64.6%的患者出现体重减轻、肌肉力量下降、无脂肪质量指数低、生物化学异常、厌食和疲劳。2年内270名患者(21.0%)发生全因死亡率。恶病质组(危险比[HR],1.494;95%置信区间[CI],1.173-1.903;P=0.001)在校正HF的严重程度后,其死亡率高于非恶病质对照组。心血管和非心血管死亡分别发生在148例(11.3%)和122例(9.3%)患者中。恶病质在心血管死亡率和非心血管死亡率中的校正HR分别为1.456(95%CI,1.048-2.023;P=0.025)和1.561(95%CI:1.086-2.243;P=0.017)。在恶病质诊断标准中,肌肉力量下降(HR,1.514;95%可信区间,1.095-2.093;P=0.012)和低脂肪游离质量指数(HR,1.424;95%置信区间,1.052-1.926;P=0.022)与高全因死亡率显著相关,但单独的体重减轻(HR,1.147;95%CI,0.895-1.471;P=0.0277)与全因死亡率之间没有显著关联。结论:通过多种评估评估的恶病质在三分之一的老年HF患者中存在,并且与更差的预后相关。恶病质的多模式评估可能有助于老年HF患者的风险分层。
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引用次数: 1
Corrigendum to I.S. Sinam et al. J of Cachexia, Sarcopenia and Muscle, 13, 3122–3136. DOI: 10.1002/jcsm.13100 I.S.Sinam等人的勘误表。恶病质,肌肉萎缩和肌肉杂志,133122-1336。DOI:10.1002/jcsm.13100。
IF 8.9 1区 医学 Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13295

In the original full paper,1 Figure 2D, we have inadvertently uploaded an incorrect figure. We came across this error during the process of data archiving. However, the correction did not affect the quantification (Figure 2D) and therefore, the original interpretation of data and conclusions remain same. Corrected data are identified in red arrow below.

Representative image of MYOG of C2C12 myotubes transfected with shPdk4 or shControl and treated with or without dexamethasone (DEX) (100 μM) for 24 h. Quantification represents the levels of the MYOG + ve cell. n = 4; number of image capture sites 20 from each group. **P < 0.01; ***P < 0.001; ****P < 0.0001. Tukey's multiple comparisons test was used for the analysed.

在原全文1 Figure 2D中,我们不小心上传了一个错误的图。我们在数据存档的过程中遇到了这个错误。然而,校正不影响量化(图2D),因此,对数据和结论的原始解释保持不变。更正后的数据如下红色箭头所示。用shPdk4或shControl转染C2C12肌管,用或不加100 μM地塞米松(DEX)处理24 h后MYOG的代表性图像。定量表示MYOG + ve细胞的水平。n = 4;图像捕获站点数量,每组20个。* * P & lt;0.01;* * * P & lt;0.001;* * * * P & lt;0.0001. 采用Tukey多重比较检验进行分析。
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引用次数: 0
Development and applicability of modified weight loss grading system in cancer: a real-world cohort study 癌症改良减肥分级系统的发展和适用性:一项现实世界的队列研究。
IF 8.9 1区 医学 Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13287
Hailun Xie, Guotian Ruan, Lishuang Wei, Heyang Zhang, Yizhong Ge, Shiqi Lin, Mengmeng Song, Qi Zhang, Xi Zhang, Ziwen Wang, Chenan Liu, Jinyu Shi, Xiaoyue Liu, Ming Yang, Xin Zheng, Yue Chen, Xiaowei Zhang, Li Deng, Hanping Shi

Background

The original weight loss grading system (WLGS) was developed in western population, which did not perform effectively in cancer patients from China. This study aimed to develop and validate the modified WLGS (mWLGS) in the prognostic assessment of cancer patients in China.

Methods

A prospective multicentre real-world cohort study involving 16 842 patients diagnosed with cancer was conducted. Cox regression was used to calculate the hazard ratios for overall survival. Logistic linear regression was used to assess the odds ratio for 90-day outcomes.

Results

We calculated survival risks for the 25 mWLGS groups and clustered the approximate survival risks. Finally, we revised the prognostic grading system for mWLGS to include five grades of 0–4. Compared with the original WLGS, the mWLGS had a better prognostic differentiation effect in predicting the prognosis of patients with cancer. The survival rate gradually deteriorated with increasing grade of mWLGS, with the survival rate of grade 0 decreasing from 76.4% to 48.2% for grade 4 (76.4 vs. 72.8 vs. 66.1 vs. 57.0 vs. 48.2%, respectively). The mWLGS provides effective prognostic stratification for most site-specific cancers, especially lung and gastrointestinal cancers. High-grade mWLGS is independently associated with an increased risk of poor quality of life and adverse 90-day outcomes. Multivariate Cox regression analysis showed that the mWLGS was an independent prognostic factor for cancer patients in the validation cohorts.

Conclusions

Compared with the original WLGS, the mWLGS can better stratify the prognosis of cancer patients. mWLGS is a useful tool for predicting survival, 90-day outcomes, and quality of life in patients with cancer. These analyses may provide new insights into the application of WLGS in cancer patients in China.

背景:最初的体重减轻分级系统(WLGS)是在西方人群中开发的,但在中国癌症患者中效果不佳。本研究旨在开发和验证改良WLGS(mWLGS)在中国癌症患者预后评估中的作用。Cox回归用于计算总生存率的危险比。Logistic线性回归用于评估90天结果的比值比。结果:我们计算了25 mWLGS组的生存风险,并对近似生存风险进行了聚类。最后,我们修订了mWLGS的预后分级系统,将0-4分为五个等级。与原始WLGS相比,mWLGS在预测癌症患者预后方面具有更好的预后分化效果。生存率随着mWLGS分级的增加而逐渐恶化,0级的生存率从76.4%降至4级的48.2%(分别为76.4对72.8对66.1对57.0对48.2%)。mWLGS为大多数位点特异性癌症,特别是肺癌和胃肠道癌症提供了有效的预后分层。高级别mWLGS与生活质量差和90天不良结果的风险增加独立相关。多因素Cox回归分析表明,mWLGS是验证队列中癌症患者的独立预后因素。结论:与原WLGS相比,mWLGS能更好地对癌症患者的预后进行分层。mWLGS是预测癌症患者生存率、90天预后和生活质量的有用工具。这些分析可能为WLGS在中国癌症患者中的应用提供新的见解。
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Journal of Cachexia, Sarcopenia and Muscle
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