Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Short-term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates","authors":"George F. Pavis,&nbsp;Doaa R. Abdelrahman,&nbsp;Andrew J. Murton,&nbsp;Benjamin T. Wall,&nbsp;Francis B. Stephens,&nbsp;Marlou L. Dirks","doi":"10.1002/jcsm.13284","DOIUrl":"10.1002/jcsm.13284","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The decline in postabsorptive and postprandial muscle protein fractional synthesis rates (FSR) does not quantitatively account for muscle atrophy during uncomplicated, short-term disuse, when atrophy rates are the highest. We sought to determine whether 2 days of unilateral knee immobilization affects mixed muscle protein fractional breakdown rates (FBR) during postabsorptive and simulated postprandial conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-three healthy, male participants (age: 22 ± 1 year; height: 179 ± 1 cm; body mass: 73.4 ± 1.5 kg; body mass index 22.8 ± 0.5 kg·m⁻²) took part in this randomized, controlled study. After 48 h of unilateral knee immobilization, primed continuous intravenous <span>l</span>-[¹⁵N]-phenylalanine and <span>l</span>-[<i>ring</i>-²H₅]-phenylalanine infusions were used for parallel determinations of FBR and FSR, respectively, in a postabsorptive (saline infusion; FAST) or simulated postprandial state (67.5 mg·kg body mass⁻¹·h⁻¹ amino acid infusion; FED). Bilateral <i>m. vastus lateralis</i> biopsies from the control (CON) and immobilized (IMM) legs, and arterialized-venous blood samples, were collected throughout.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amino acid infusion rapidly increased plasma phenylalanine (59 ± 9%), leucine (76 ± 5%), isoleucine (109 ± 7%) and valine (42 ± 4%) concentrations in FED only (all <i>P</i> &lt; 0.001), which was sustained for the remainder of infusion. Serum insulin concentrations peaked at 21.8 ± 2.2 mU·L⁻¹ at 15 min in FED only (<i>P</i> &lt; 0.001) and were 60% greater in FED than FAST (<i>P</i> &lt; 0.01). Immobilization did not influence FBR in either FAST (CON: 0.150 ± 0.018; IMM: 0.143 ± 0.017%·h⁻¹) or FED (CON: 0.134 ± 0.012; IMM: 0.160 ± 0.018%·h⁻¹; all effects <i>P</i> &gt; 0.05). However, immobilization decreased FSR (<i>P</i> &lt; 0.05) in both FAST (0.071 ± 0.004 vs. 0.086 ± 0.007%·h⁻¹; IMM vs CON, respectively) and FED (0.066 ± 0.016 vs. 0.119 ± 0.016%·h⁻¹; IMM vs CON, respectively). Consequently, immobilization decreased net muscle protein balance (<i>P</i> &lt; 0.05) and to a greater extent in FED (CON: −0.012 ± 0.025; IMM: −0.095 ± 0.023%·h⁻¹; <i>P</i> &lt; 0.05) than FAST (CON: −0.064 ± 0.020; IMM: −0.072 ± 0.017%·h⁻¹).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We conclude that merely 2 days of leg immobilization does not modulate postabsorptive and s","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2064-2075"},"PeriodicalIF":8.9,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9773108","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":"Association of intrinsic capacity with incidence and mortality of cardiovascular disease: Prospective study in UK Biobank","authors":"Robinson Ramírez-Vélez,&nbsp;Maria Iriarte-Fernández,&nbsp;Guzman Santafé,&nbsp;Armando Malanda,&nbsp;John R. Beard,&nbsp;Antonio Garcia-Hermoso,&nbsp;Mikel Izquierdo","doi":"10.1002/jcsm.13283","DOIUrl":"10.1002/jcsm.13283","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The World Health Organization proposed the concept of intrinsic capacity (IC; the composite of all the physical and mental capacities of the individual) as central for healthy ageing. However, little research has investigated the interaction and joint associations of IC with cardiovascular disease (CVD) incidence and CVD mortality in middle- and older-aged adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from 443 130 UK Biobank participants, we analysed seven biomarkers capturing the level of functioning of five domains of IC to calculate a total IC score (ranging from 0 [better IC] to +4 points [poor IC]). Associations between IC score and incidence of six long-term CVD conditions (hypertension, stroke/transient ischaemic attack stroke, peripheral vascular disease, atrial fibrillation/flutter, coronary artery disease and heart failure), and grouped mortality from these conditions were estimated using Cox proportional models, with a 1-year landmark analysis to triangulate the findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over 10.6 years of follow-up, CVD morbidity grouped (<i>n</i> = 384 380 participants for the final analytic sample) was associated with IC scores (0 to +4): mean hazard ratio (HR) [95% confidence interval, CI] 1.11 [1.08–1.14], 1.20 [1.16–1.24], 1.29 [1.23–1.36] and 1.56 [1.45–1.59] in men (C-index = 0.68), and 1.17 [1.13–1.20], 1.30 [1.26–1.36], 1.52 [1.45–1.59] and 1.78 [1.67–1.89] in women (C-index = 0.70). In regard to mortality, our results indicated that the higher IC score (+4 points) was associated with a significant increase in subsequent CVD mortality (mean HR [95% CI]: 2.10 [1.81–2.43] in men [C-index = 0.75] and 2.29 [1.85–2.84] in women [C-index = 0.78]). Results of all sensitivity analyses by full sample, sex and age categories were largely consistent independent of major confounding factors (<i>P</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IC deficit score is a powerful predictor of functional trajectories and vulnerabilities of the individual in relation to CVD incidence and premature death. Monitoring an individual's IC score may provide an early-warning system to initiate preventive efforts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2054-2063"},"PeriodicalIF":8.9,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129020","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":"Iron deficiency is related to lower muscle mass in community-dwelling individuals and impairs myoblast proliferation","authors":"Joanna Sophia J. Vinke,&nbsp;Alan R. Gorter,&nbsp;Michele F. Eisenga,&nbsp;Wendy A. Dam,&nbsp;Peter van der Meer,&nbsp;Jacob van den Born,&nbsp;Stephan J.L. Bakker,&nbsp;Martijn F. Hoes,&nbsp;Martin H. de Borst","doi":"10.1002/jcsm.13277","DOIUrl":"https://doi.org/10.1002/jcsm.13277","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population-based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a population-based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24-h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5-bromo-2′-deoxy-uridine ELISA assay. Myocyte differentiation was assessed using Myh7-stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence-activated cell sorting. RNA sequencing (RNAseq) was used to identify ID-related gene and pathway enrichment in myoblasts and myocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants in the lowest age- and sex-specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25–2.10, <i>P</i> &lt; 0.001) or transferrin saturation (OR 1.34, 95% CI 1.03–1.75, <i>P</i> = 0.03) had a significantly higher risk of being in the lowest age- and sex-specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs-CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine-induced ID reduced myoblast proliferation rate (<i>P</i>-trend &lt;0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (−52%, <i>P</i> &lt; 0.001) and tended to reduce mitochondrial oxygen consumption capacity (−28%, <i>P</i> = 0.10). Deferoxamine induced gene expression of cellular atrophy markers <i>Trim63</i> (+20%, <i>P</i> = 0.002) and <i>Fbxo32</i> (+27%, <i>P</i> = 0.048), which was reversed by ferric citrate (−31%, <i>P</i> = 0.04 and −26%, <i>P</i> = 0.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in gly","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1865-1879"},"PeriodicalIF":8.9,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6111097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hand grip strength in patients with advanced cancer: A prospective study","authors":"Sara Hadzibegovic,&nbsp;Jan Porthun,&nbsp;Alessia Lena,&nbsp;Pia Weinl?nder,&nbsp;Laura C. Lück,&nbsp;Sophia K. Potthoff,&nbsp;Lukas R?snick,&nbsp;Ann-Kathrin Fr?hlich,&nbsp;Luisa Valentina Ramer,&nbsp;Frederike Sonntag,&nbsp;Ursula Wilkenshoff,&nbsp;Johann Ahn,&nbsp;Ulrich Keller,&nbsp;Lars Bullinger,&nbsp;Amir A. Mahabadi,&nbsp;Matthias Totzeck,&nbsp;Tienush Rassaf,&nbsp;Stephan von Haehling,&nbsp;Andrew J.S. Coats,&nbsp;Stefan D. Anker,&nbsp;Eric J. Roeland,&nbsp;Ulf Landmesser,&nbsp;Markus S. Anker","doi":"10.1002/jcsm.13248","DOIUrl":"https://doi.org/10.1002/jcsm.13248","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hand grip strength (HGS) is a widely used functional test for the assessment of strength and functional status in patients with cancer, in particular with cancer cachexia. The aim was to prospectively evaluate the prognostic value of HGS in patients with mostly advanced cancer with and without cachexia and to establish reference values for a European-based population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective study, 333 patients with cancer (85% stage III/IV) and 65 healthy controls of similar age and sex were enrolled. None of the study participants had significant cardiovascular disease or active infection at baseline. Repetitive HGS assessment was performed using a hand dynamometer to measure the maximal HGS (kilograms). Presence of cancer cachexia was defined when patients had ≥5% weight loss within 6 months or when body mass index was &lt;20.0 kg/m² with ≥2% weight loss (Fearon's criteria). Cox proportional hazard analyses were performed to assess the relationship of maximal HGS to all-cause mortality and to determine cut-offs for HGS with the best predictive power. We also assessed associations with additional relevant clinical and functional outcome measures at baseline, including anthropometric measures, physical function (Karnofsky Performance Status and Eastern Cooperative of Oncology Group), physical activity (4-m gait speed test and 6-min walk test), patient-reported outcomes (EQ-5D-5L and Visual Analogue Scale appetite/pain) and nutrition status (Mini Nutritional Assessment).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age was 60 ± 14 years; 163 (51%) were female, and 148 (44%) had cachexia at baseline. Patients with cancer showed 18% lower HGS than healthy controls (31.2 ± 11.9 vs. 37.9 ± 11.6 kg, <i>P</i> &lt; 0.001). Patients with cancer cachexia had 16% lower HGS than those without cachexia (28.3 ± 10.1 vs. 33.6 ± 12.3 kg, <i>P</i> &lt; 0.001). Patients with cancer were followed for a mean of 17 months (range 6–50), and 182 (55%) patients died during follow-up (2-year mortality rate 53%) (95% confidence interval 48–59%). Reduced maximal HGS was associated with increased mortality (per −5 kg; hazard ratio [HR] 1.19; 1.10–1.28; <i>P</i> &lt; 0.0001; independently of age, sex, cancer stage, cancer entity and presence of cachexia). HGS was also a predictor of mortality in patients with cachexia (per −5 kg; HR 1.20; 1.08–1.33; <i>P</i> = 0.001) and without cachexia (per −5 kg; HR 1.18; 1.04–1.34; <i>P</i> = 0.010). The cut-off for maximal HGS with the best predictive power for poor survival was &lt;25.1 kg for females (sensitivity 54%, specificity 63%)","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1682-1694"},"PeriodicalIF":8.9,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6151241","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":"Comment on ‘Causal linkage of tobacco smoking with ageing: Mendelian randomization analysis towards telomere attrition and sarcopenia’ by Park et al.","authors":"Mingchong Liu,&nbsp;Chensong Yang,&nbsp;Yutao Pan,&nbsp;Guixin Sun","doi":"10.1002/jcsm.13279","DOIUrl":"https://doi.org/10.1002/jcsm.13279","url":null,"abstract":"<p>As we all know, it has been proven that tobacco smoking is associated with many diseases, including sarcopenia.<span>¹</span> However, tobacco smoking as a lifestyle always affects our bodies for a quite long time, which is a great challenge for researchers to conduct a randomized controlled trial to identify the causal roles of tobacco smoking in diseases. We therefore read the recent paper by Park et al. This is a well-designed Mendelian randomization (MR) study, using genome-wide association studies (GWASs), which may prove the evidence of causal associations of tobacco smoking with telomere attrition and sarcopenia. These findings suggested that ever being a regular smoker in life (smoking initiation) was causally associated with shorter leucocyte telomere length (LTL), lower appendicular lean mass index (ALM), slower walking pace, and lower time spent on moderate-to-vigorous physical activity (MVPA).<span>²</span></p><p>However, in this study, the high sample overlapping rate in the two-sample mendelian randomization raised concern about the conclusion: the data sources in the study were from UK Biobank (<i>N</i> = 337 138, for aging and sarcopenia) and a GWAS meta-analysis study named GSCAN (<i>N</i> = 1.2 million, for tobacco smoking).<span>³</span> We carefully read the raw study of the GSCAN, and unfortunately, in the 1.2 million samples, 383 613 were from UK Biobank. According to the calculation methods for the maximum estimated value for sample overlapping rate, the cohort of aging and sarcopenia (337 138 samples) may be fully overlapped with samples for smoking (383 613 samples), which means the maximum estimated sample overlapping rate might be 100%. It was the violation of the essential assumptions of two-sample MR. The bias caused by sample overlapping should not be ignored.<span>⁴</span></p><p>Interestingly, the raw data provided by GSCAN contains a dataset without UK Biobank cohorts (https://conservancy.umn.edu/handle/11299/201564). Therefore, using the GSCAN data without UK Biobank, we tried to re-perform the MR study by Park et al. Briefly, the data including 848 460 individuals for exposure (tobacco smoking) were from the GSCAN data without UK Biobank individuals. For outcomes, similar to Park's study, we used the summary GWAS data of the UK Biobank from the IEU database.<span>⁵</span> Except for handgrip strength, the phenotypes of other outcomes were as same as the previous study: including LTL (<i>N</i> = 472 174, datasets ID: ieu-b-4879), adjusted appendicular lean mass (<i>N</i> = 450 243, datasets ID: GCST90000025), walking pace (<i>N</i> = 459 915, datasets ID: ukb-b-4711), moderate to vigorous physical activity (<i>N</i> = 377 234, datasets ID: GCST006097). In the study by Park et al., handgrip strength was defined as the average value of two hands. Because we did not have access to the detailed UK Biobank data, our study's phenotypes of handgrip strength were d","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1912-1914"},"PeriodicalIF":8.9,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5688040","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":"Respiratory sarcopenia is a predictor of all-cause mortality in community-dwelling older adults—The Otassha Study","authors":"Takeshi Kera,&nbsp;Hisashi Kawai,&nbsp;Manami Ejiri,&nbsp;Kumiko Ito,&nbsp;Hirohiko Hirano,&nbsp;Yoshinori Fujiwara,&nbsp;Kazushige Ihara,&nbsp;Shuichi Obuchi","doi":"10.1002/jcsm.13266","DOIUrl":"https://doi.org/10.1002/jcsm.13266","url":null,"abstract":"<p>As individuals age, skeletal muscle mass and function, including lean body mass and grip strength, and respiratory muscle mass and strength, tend to decline.<span>^{1, 2}</span> The term ‘respiratory sarcopenia’ emerged during a discussion on sarcopenia. Respiratory sarcopenia should encompass respiratory muscle mass and strength or function to adhere to the original sarcopenia definition, which considers whole-body muscle mass, grip strength, and gait speed. However, the decreasing respiratory muscle mass associated with aging has not been adequately discussed. The concept may appear simple; however, defining respiratory sarcopenia has not been extensively explored.</p><p>Inspiratory and expiratory maximal mouth pressure measurement as direct evidence of respiratory muscle strength is simple; however, access to relevant measuring equipment is limited. Moreover, evaluating respiratory muscle mass is challenging, and the respiratory sarcopenia using low respiratory muscle mass cannot be virtually established. Therefore, we proposed defining respiratory sarcopenia using the peak expiratory flow rate (PEFR) as an alternative to directly measuring respiratory muscle strength.<span>³</span> Subsequently, the Japanese Working Group of Respiratory Sarcopenia of the Japanese Association of Rehabilitation Nutrition (JARN) published criteria for respiratory sarcopenia, which was defined based on a decline in the maximal mouth pressure and respiratory muscle mass and the presence of whole-body-sarcopenia, as measured using skeletal muscle mass, strength, and physical performance.<span>⁴</span> However, this definition has not been established due to a lack of consensus. Moreover, to the best of our knowledge, the future health-related outcomes of respiratory sarcopenia have never been evaluated. Therefore, this survey confirmed whether respiratory sarcopenia, defined using PEFR and the JARN criteria, is associated with future mortality among community-dwelling older adults.</p><p>We assessed respiratory sarcopenia-related mortality after a 5-year follow-up of 470 participants (185 men aged 75.2 ± 5.5 years and 285 women aged 74.2 ± 5.4 years) who participated in a comprehensive health checkup program called ‘The Otassha Study’ conducted in the Tokyo Metropolitan Institute for Geriatrics and Gerontology in 2015. Participants who underwent spirometry and sarcopenia assessment were included; however, patients with chronic obstructive pulmonary disease (COPD) were excluded.</p><p>An electronic spirometer (Autospiro AS-507, Minato, Osaka, Japan) was used to measure pulmonary function. The PEFR as a percentage of the predicted value (%PEFR), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), VC as a percentage of the predicted value (%VC), FVC as a percentage of the predicted value (%FVC), lower limit of normal FVC (FVC_LLN), and FEV₁/FVC were assessed.</p><p>A","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1894-1899"},"PeriodicalIF":8.9,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6232689","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":"RhoA/ROCK signalling activated by ARHGEF3 promotes muscle weakness via autophagy in dystrophic mdx mice","authors":"Jae-Sung You,&nbsp;Yongdeok Kim,&nbsp;Soohyun Lee,&nbsp;Rashid Bashir,&nbsp;Jie Chen","doi":"10.1002/jcsm.13278","DOIUrl":"https://doi.org/10.1002/jcsm.13278","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, leads to progressive and fatal muscle weakness through yet-to-be-fully deciphered molecular perturbations. Emerging evidence implicates RhoA/Rho-associated protein kinase (ROCK) signalling in DMD pathology, yet its direct role in DMD muscle function, and related mechanisms, are unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three-dimensionally engineered dystrophin-deficient <i>mdx</i> skeletal muscles and <i>mdx</i> mice were used to test the role of ROCK in DMD muscle function <i>in vitro</i> and <i>in situ</i>, respectively. The role of ARHGEF3, one of the RhoA guanine nucleotide exchange factors (GEFs), in RhoA/ROCK signalling and DMD pathology was examined by generating <i>Arhgef3</i> knockout <i>mdx</i> mice. The role of RhoA/ROCK signalling in mediating the function of ARHGEF3 was determined by evaluating the effects of wild-type or GEF-inactive ARHGEF3 overexpression with ROCK inhibitor treatment. To gain more mechanistic insights, autophagy flux and the role of autophagy were assessed in various conditions with chloroquine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inhibition of ROCK with Y-27632 improved muscle force production in 3D-engineered <i>mdx</i> muscles (+25% from three independent experiments, <i>P</i> &lt; 0.05) and in mice (+25%, <i>P</i> &lt; 0.001). Unlike suggested by previous studies, this improvement was independent of muscle differentiation or quantity and instead related to increased muscle quality. We found that ARHGEF3 was elevated and responsible for RhoA/ROCK activation in <i>mdx</i> muscles, and that depleting ARHGEF3 in <i>mdx</i> mice restored muscle quality (up to +36%, <i>P</i> &lt; 0.01) and morphology without affecting regeneration. Conversely, overexpressing ARHGEF3 further compromised <i>mdx</i> muscle quality (−13% vs. empty vector control, <i>P</i> &lt; 0.01) in GEF activity- and ROCK-dependent manner. Notably, ARHGEF3/ROCK inhibition exerted the effects by rescuing autophagy which is commonly impaired in dystrophic muscles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings uncover a new pathological mechanism of muscle weakness in DMD involving the ARHGEF3-ROCK-autophagy pathway and the therapeutic potential of targeting ARHGEF3 in DMD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1880-1893"},"PeriodicalIF":8.9,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5673867","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":"Association between sarcopenia and frailty in elderly patients with chronic kidney disease","authors":"Che Wang,&nbsp;Xinru Guo,&nbsp;Xieguanxuan Xu,&nbsp;Shuang Liang,&nbsp;Wenling Wang,&nbsp;Fanglei Zhu,&nbsp;Siyang Wang,&nbsp;Jie Wu,&nbsp;Li Zhang,&nbsp;Xuefeng Sun,&nbsp;Xiangmei Chen,&nbsp;Guangyan Cai,&nbsp;The Chinese observational prospective study of ageing population with chronic kidney disease (C-OPTION)","doi":"10.1002/jcsm.13275","DOIUrl":"https://doi.org/10.1002/jcsm.13275","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non-dialysis patients. Therefore, this study aimed to determine frailty-associated factors in elderly CKD stage I–IV patients, expected to early identify and intervene in the frailty of elderly CKD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 774 elderly CKD I–IV patients (&gt;60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven hundred seventy-four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m². The prevalence of sarcopenia was 30.6%. The FI exhibited a right-skewed distribution. The age-related slope of FI was 1.4% per year on a logarithmic scale (<i>r</i>² = 0.706, 95% CI 0.9, 1.8, <i>P</i> &lt; 0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR = 1.06, 95% CI 1.00, 1.12, <i>P</i> = 0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II–IV, low level of serum albumin and increased waist–hip ratio were significantly associated with high FI status, while advanced age and CKD stage III–IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sarcopenia was independently associated with an increased risk for frailty in elderly CKD I-IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist–hip ratio and low serum albumin level should be assessed for frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1855-1864"},"PeriodicalIF":8.9,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6148134","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":"Machine learning models to predict outcomes at 30-days using Global Leadership Initiative on Malnutrition combinations with and without muscle mass in people with cancer","authors":"Nicole Kiss,&nbsp;Belinda Steer,&nbsp;Marian de van der Schueren,&nbsp;Jenelle Loeliger,&nbsp;Roohallah Alizadehsani,&nbsp;Lara Edbrooke,&nbsp;Irene Deftereos,&nbsp;Erin Laing,&nbsp;Abbas Khosravi","doi":"10.1002/jcsm.13259","DOIUrl":"https://doi.org/10.1002/jcsm.13259","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Equipment to assess muscle mass is not available in all health services. Yet we have limited understanding of whether applying the Global Leadership Initiative on Malnutrition (GLIM) criteria without an assessment of muscle mass affects the ability to predict adverse outcomes. This study used machine learning to determine which combinations of GLIM phenotypic and etiologic criteria are most important for the prediction of 30-day mortality and unplanned admission using combinations including and excluding low muscle mass.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a cohort of 2801 participants from two cancer malnutrition point prevalence studies, we applied the GLIM criteria with and without muscle mass. Phenotypic criteria were assessed using ≥5% unintentional weight loss, body mass index, subjective assessment of muscle stores from the PG-SGA. Aetiologic criteria included self-reported reduced food intake and inflammation (metastatic disease). Machine learning approaches were applied to predict 30-day mortality and unplanned admission using models with and without muscle mass.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants with missing data were excluded, leaving 2494 for analysis [49.6% male, mean (SD) age: 62.3 (14.2) years]. Malnutrition prevalence was 19.5% and 17.5% when muscle mass was included and excluded, respectively. However, 48 (10%) of malnourished participants were missed if muscle mass was excluded. For the nine GLIM combinations that excluded low muscle mass the most important combinations to predict mortality were (1) weight loss and inflammation and (2) weight loss and reduced food intake. Machine learning metrics were similar in models excluding or including muscle mass to predict mortality (average accuracy: 84% vs. 88%; average sensitivity: 41% vs. 38%; average specificity: 85% vs. 89%). Weight loss and reduced food intake was the most important combination to predict unplanned hospital admission. Machine learning metrics were almost identical in models excluding or including muscle mass to predict unplanned hospital admission, with small differences observed only if reported to one decimal place (average accuracy: 77% vs. 77%; average sensitivity: 29% vs. 29%; average specificity: 84% vs. 84%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate predictive ability is maintained, although the ability to identify all malnourished patients is compromised, when muscle mass is excluded from the GLIM diagnosis. This has important implications for assessme","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1815-1823"},"PeriodicalIF":8.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5909718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weight variability, physical functioning and incident disability in older adults","authors":"Katie J. McMenamin,&nbsp;Tamara B. Harris,&nbsp;Joshua F. Baker","doi":"10.1002/jcsm.13239","DOIUrl":"https://doi.org/10.1002/jcsm.13239","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study aimed to determine if greater variability in body mass index (BMI) is associated with declines in physical functioning and incident disability in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Included were participants from the Health, Aging and Body Composition Study who had semi-annual BMI data during the first 3 years of follow-up. Participants were categorized into quintiles of BMI variability, using two methods. The first method used average successive variability, whereas the second method adjusted these values to remove the variability due to net change in BMI over the 3-year period. Linear regression was used to assess the relationship between the two measures of BMI variability and net changes in BMI, fat mass index, appendicular lean mass index, and Health, Aging and Body Composition Physical Performance Score during the first 3 years of the study. Cox proportional hazard models were used to assess the relationship of BMI variability with the subsequent incidence of new disability, adjusting for confounding factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 2121 participants, those in the highest BMI variability quintile were more likely to lose both body mass (<i>β</i>: −0.086 [95% confidence interval, CI: −0.133, −0.040], <i>P</i> &lt; 0.01) and fat mass (<i>β</i>: −0.059 [95% CI: −0.117, −0.002], <i>P</i> = 0.04) and had greater declines in physical performance score (<i>β</i>: −0.094 [95% CI: −0.162, −0.026], <i>P</i> &lt; 0.01) compared to participants with the least variability in BMI. Participants with high BMI variability also had higher rates of incident disability (hazard ratio: 1.36 [95% CI: 1.07, 1.72], <i>P</i> = 0.01), independent of net BMI change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>BMI variability in older adults is associated with decline in physical performance and incident disability. This relationship cannot be explained by net weight loss alone, supporting it as an independent feature of frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1648-1656"},"PeriodicalIF":8.9,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5930474","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}