Tai-Anh Vu, Samuel T. H. Chew, Sahil Thakur, Hiromi Yee, Ryan E. K. Man, Eva K. Fenwick, Amudha Aravindhan, Belicia Lim Jia Yi, Preeti Gupta, Ecosse L. Lamoureux
<div> <section> <h3> Background</h3> <p>To determine the associations between deficits in the visual function system, comprising visual acuity (VAI), contrast sensitivity (CSI), colour vision (CVI), depth perception (DPI) and visual field (VFI) impairments, as well as poor muscle health in an older Asian population.</p> </section> <section> <h3> Methods</h3> <p>We used data from the baseline assessment of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER; 2017–2022) study. Visual function deficits included near visual acuity impairment (NVAI) (> N8), distance visual acuity impairment–DVAI (< 20/40 or > 0.3 logMAR), CSI (< 1.55 logCS), CVI (1 or more major crossings on Farnsworth D-15), DPI (≥ 150 arc sec) and VFI (Hodapp, Parish and Anderson criteria). Poor muscle health was defined as the presence of either low muscle mass (appendicular-lean-mass/height<sup>2</sup> of < 7 kg/m<sup>2</sup> for males and < 5.4 kg/m<sup>2</sup> for females), or low muscle strength (handgrip strength < 28 kg and < 18 kg, in men and women, respectively) or low physical performance (gait speed of < 1.0 m/s). Regression models were utilized to evaluate the associations between visual deficits and poor muscle health after adjusting for sociodemographic, clinical and lifestyle factors.</p> </section> <section> <h3> Results</h3> <p>Of the 2199 included participants (1105 Chinese, 580 Malays and 514 Indians; mean age ± SD: 72.9 ± 8.3 years; 54.3% female), 91.7% had poor muscle health. In multivariable analyses, DVAI (odds ratio [OR]: 2.01; 95%CI: 1.19, 3.40), NVAI (OR: 2.48; 95%CI: 1.31, 4.71), CSI (OR: 1.77; 95%CI: 1.18, 2.64) and CVI (OR: 1.95; 95%CI: 1.07, 3.59) were significantly associated with approximately twice the odds of poor muscle health. Moreover, the likelihood of poor muscle health significantly increased with the severity of visual function deficits (all <i>p</i> trend < 0.05). Participants with moderate–severe DVAI, NVAI, CSI and DPI had much higher odds (OR range: 2.24–5.78) of poor muscle health compared to those without these impairments. No associations were found between VFI and poor muscle health. The leading cause of VAI (near or distance) or CSI in those with poor muscle health was cataract (50.5%).</p> </section> <section> <h3> Conclusions</h3> <p>Older adults with visual function deficits, especially moderate–severe impairment in DVAI, NVAI and CSI, have a much higher likelihood of poor muscle health. Importantly, most cases of VAI or CSI were treatable. These findings support targeted clin
{"title":"The Association Between Visual Function Deficits and Poor Muscle Health in Multiethnic Older Asians: The Pioneer Study","authors":"Tai-Anh Vu, Samuel T. H. Chew, Sahil Thakur, Hiromi Yee, Ryan E. K. Man, Eva K. Fenwick, Amudha Aravindhan, Belicia Lim Jia Yi, Preeti Gupta, Ecosse L. Lamoureux","doi":"10.1002/rco2.70020","DOIUrl":"https://doi.org/10.1002/rco2.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To determine the associations between deficits in the visual function system, comprising visual acuity (VAI), contrast sensitivity (CSI), colour vision (CVI), depth perception (DPI) and visual field (VFI) impairments, as well as poor muscle health in an older Asian population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from the baseline assessment of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER; 2017–2022) study. Visual function deficits included near visual acuity impairment (NVAI) (> N8), distance visual acuity impairment–DVAI (< 20/40 or > 0.3 logMAR), CSI (< 1.55 logCS), CVI (1 or more major crossings on Farnsworth D-15), DPI (≥ 150 arc sec) and VFI (Hodapp, Parish and Anderson criteria). Poor muscle health was defined as the presence of either low muscle mass (appendicular-lean-mass/height<sup>2</sup> of < 7 kg/m<sup>2</sup> for males and < 5.4 kg/m<sup>2</sup> for females), or low muscle strength (handgrip strength < 28 kg and < 18 kg, in men and women, respectively) or low physical performance (gait speed of < 1.0 m/s). Regression models were utilized to evaluate the associations between visual deficits and poor muscle health after adjusting for sociodemographic, clinical and lifestyle factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 2199 included participants (1105 Chinese, 580 Malays and 514 Indians; mean age ± SD: 72.9 ± 8.3 years; 54.3% female), 91.7% had poor muscle health. In multivariable analyses, DVAI (odds ratio [OR]: 2.01; 95%CI: 1.19, 3.40), NVAI (OR: 2.48; 95%CI: 1.31, 4.71), CSI (OR: 1.77; 95%CI: 1.18, 2.64) and CVI (OR: 1.95; 95%CI: 1.07, 3.59) were significantly associated with approximately twice the odds of poor muscle health. Moreover, the likelihood of poor muscle health significantly increased with the severity of visual function deficits (all <i>p</i> trend < 0.05). Participants with moderate–severe DVAI, NVAI, CSI and DPI had much higher odds (OR range: 2.24–5.78) of poor muscle health compared to those without these impairments. No associations were found between VFI and poor muscle health. The leading cause of VAI (near or distance) or CSI in those with poor muscle health was cataract (50.5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Older adults with visual function deficits, especially moderate–severe impairment in DVAI, NVAI and CSI, have a much higher likelihood of poor muscle health. Importantly, most cases of VAI or CSI were treatable. These findings support targeted clin","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Testosterone is an important anabolic in humans, but its conversion to dihydrotestosterone in skin and prostate and to oestradiol in adipose tissue also yields untoward androgenic and estrogenic effects. It was therefore a breakthrough of considerable interest, when Dalton and colleagues in 1998 reported the synthesis of non-steroidal arylpropionamide ligands for the androgen receptor. Three of these newly discovered ligands bound the receptor with affinity similar to dihydrotestosterone and mimicked its effects on receptor-mediated transcriptional activation, thus demonstrating agonist activity [<span>1</span>]. Since then, a number of different non-steroidal chemical scaffolds have been developed to mimic androgen receptor ligands, including bicyclic hydantoins, bicyclic thiohydantoins, imidazolopyrazoles, benzimidazoles, anilines and quinolinones. The umbrella term for these substances is selective androgen-receptor modulators (SARMs), and they were developed with the aim of preserving anabolic effects in muscle and bone while reducing androgenic side effects (e.g., prostate stimulation, virilization and gynecomastia) and other safety concerns [<span>2</span>].</p><p>One of the SARMs that has seen considerable research efforts over the last 25 years is enobosarm (GTx-024), also known as ostarine (Figure 1) [<span>3</span>]. The drug was initially licensed and advanced by GTx Inc. (Memphis, TN) for age-related muscle loss and cachexia. In 2007, GTx even struck a large SARM collaboration with Merck to pursue the treatment of sarcopenia/cachexia and other musculoskeletal conditions [<span>4</span>]. Early trials were indeed encouraging: A Phase II randomized controlled trial in healthy elderly men and postmenopausal women (<i>n</i> = 120) showed dose-dependent gains in lean body mass (LBM) and better stair-climb power over 12 weeks [<span>5</span>]. A Phase II cancer-cachexia trial (<i>n</i> = 159) improved LBM with signals in stair-climb power, both in the 1 and 3 mg daily arm, but no signal in the placebo group [<span>6</span>]. The authors concluded that ‘enobosarm might lead to improvements in LBM, without the toxic effects associated with androgens and progestational agents’. This was followed by two near-identical Phase III studies in non-small cell lung cancer (differences mainly in chemotherapy backbone)—POWER-1 and POWER-2—designed with the US Food and Drug Administration (FDA) to use co-primary responder endpoints combining LBM and stair-climb power [<span>7, 8</span>]. It was a major setback when it became clear that both programmes increased LBM but failed to deliver consistent, clinically meaningful functional gains, and thus no approval followed. Subsequent pursuit in stress urinary incontinence (ASTRID, Phase II) was negative [<span>9</span>], reinforcing the lack of approvable benefit on functional endpoints [<span>10</span>]. Broader commentary has since emphasized how regulator-preferred functional endpoints—and safety expect
{"title":"Enobosarm in Muscle Wasting: The Rest of the Story","authors":"Stephan von Haehling","doi":"10.1002/rco2.70027","DOIUrl":"https://doi.org/10.1002/rco2.70027","url":null,"abstract":"<p>Testosterone is an important anabolic in humans, but its conversion to dihydrotestosterone in skin and prostate and to oestradiol in adipose tissue also yields untoward androgenic and estrogenic effects. It was therefore a breakthrough of considerable interest, when Dalton and colleagues in 1998 reported the synthesis of non-steroidal arylpropionamide ligands for the androgen receptor. Three of these newly discovered ligands bound the receptor with affinity similar to dihydrotestosterone and mimicked its effects on receptor-mediated transcriptional activation, thus demonstrating agonist activity [<span>1</span>]. Since then, a number of different non-steroidal chemical scaffolds have been developed to mimic androgen receptor ligands, including bicyclic hydantoins, bicyclic thiohydantoins, imidazolopyrazoles, benzimidazoles, anilines and quinolinones. The umbrella term for these substances is selective androgen-receptor modulators (SARMs), and they were developed with the aim of preserving anabolic effects in muscle and bone while reducing androgenic side effects (e.g., prostate stimulation, virilization and gynecomastia) and other safety concerns [<span>2</span>].</p><p>One of the SARMs that has seen considerable research efforts over the last 25 years is enobosarm (GTx-024), also known as ostarine (Figure 1) [<span>3</span>]. The drug was initially licensed and advanced by GTx Inc. (Memphis, TN) for age-related muscle loss and cachexia. In 2007, GTx even struck a large SARM collaboration with Merck to pursue the treatment of sarcopenia/cachexia and other musculoskeletal conditions [<span>4</span>]. Early trials were indeed encouraging: A Phase II randomized controlled trial in healthy elderly men and postmenopausal women (<i>n</i> = 120) showed dose-dependent gains in lean body mass (LBM) and better stair-climb power over 12 weeks [<span>5</span>]. A Phase II cancer-cachexia trial (<i>n</i> = 159) improved LBM with signals in stair-climb power, both in the 1 and 3 mg daily arm, but no signal in the placebo group [<span>6</span>]. The authors concluded that ‘enobosarm might lead to improvements in LBM, without the toxic effects associated with androgens and progestational agents’. This was followed by two near-identical Phase III studies in non-small cell lung cancer (differences mainly in chemotherapy backbone)—POWER-1 and POWER-2—designed with the US Food and Drug Administration (FDA) to use co-primary responder endpoints combining LBM and stair-climb power [<span>7, 8</span>]. It was a major setback when it became clear that both programmes increased LBM but failed to deliver consistent, clinically meaningful functional gains, and thus no approval followed. Subsequent pursuit in stress urinary incontinence (ASTRID, Phase II) was negative [<span>9</span>], reinforcing the lack of approvable benefit on functional endpoints [<span>10</span>]. Broader commentary has since emphasized how regulator-preferred functional endpoints—and safety expect","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas J. Cartledge, Qian Yue Tan, Liam Jones, Taeko Becque, Kinda Ibrahim, Stephen Eu Ruen Lim
<div> <section> <h3> Background</h3> <p>Acute sarcopenia in hospitalised older adults is associated with poor outcomes, such as functional decline, increased risk of falls and prolonged hospital stays. Despite this, its development among older inpatients remains poorly understood. We aimed to quantify the effects of acute hospitalisation on sarcopenia outcomes in older adults.</p> </section> <section> <h3> Methods</h3> <p>MEDLINE, EMBASE, CINAHL and Web of Science were searched from inception until January 2025. Studies that included acutely admitted patients aged 65 years or older and reported changes in at least one measure of sarcopenia during hospitalisation were included. Barthel Index was also included. A random-effects meta-analysis was undertaken.</p> </section> <section> <h3> Results</h3> <p>Fifty-five eligible studies were included, with a participant mean age of 82.2 years (<i>n</i> = 14 919 participants). Our meta-analysis showed grip strength and chair-to-stand performance to significantly increase during hospitalisation (standard mean difference [SMD] = 0.06, 95% confidence interval [CI]: 0.00; 0.13, <i>I</i><sup>2</sup> = 3%, <i>p</i> = 0.05 and SMD = 0.23, 95% CI: 0.13; 0.33, <i>I</i><sup>2</sup> = 0%, <i>p</i> < 0.01, respectively). No physical performance measure showed a significant change. Muscle mass showed no change when measured by bioelectrical impedance analysis (SMD = 0.01, 95% CI: −0.09; 0.08, <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.86). There were insufficient studies using MRI (<i>n</i> = 2) or DEXA (<i>n</i> = 1) to perform a meta-analysis. Individual studies showed a significant decrease in mid-thigh muscle area (cm<sup>2</sup>) by MRI (mean difference [MD] = −3.9, <i>p</i> < 0.01) and a significant decrease in leg lean mass (kg) by DEXA (MD = −0.16, <i>p</i> < 0.05). Barthel Index score significantly increased from admission to discharge (SMD = 0.26, 95% CI: 0.06; 0.46, <i>I</i><sup>2</sup> = 98.0%, <i>p</i> = 0.01) but significantly decreased from preadmission to discharge (SMD = −0.66, 95% CI: −0.92; −0.39, <i>I</i><sup>2</sup> = 97.5%, <i>p</i> < 0.001). Both age and hospital length of stay had no effect on grip strength (<i>p</i> = 0.615 and <i>p</i> = 0.096) or Barthel Index (<i>p</i> = 0.835 and <i>p</i> = 0.279).</p> </section> <section> <h3> Conclusions</h3> <p>This review has shown that grip strength improves during hospitalisation and decreases in muscle mass are observed when measured using MRI or DEXA. Muscle strength and physical performance assessed on admission are poor indicators of baseli
{"title":"The Effects of Acute Hospitalisation on the Characteristics of Acute Sarcopenia in Older Adults: A Systematic Review and Meta-Analysis","authors":"Thomas J. Cartledge, Qian Yue Tan, Liam Jones, Taeko Becque, Kinda Ibrahim, Stephen Eu Ruen Lim","doi":"10.1002/rco2.70024","DOIUrl":"https://doi.org/10.1002/rco2.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute sarcopenia in hospitalised older adults is associated with poor outcomes, such as functional decline, increased risk of falls and prolonged hospital stays. Despite this, its development among older inpatients remains poorly understood. We aimed to quantify the effects of acute hospitalisation on sarcopenia outcomes in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MEDLINE, EMBASE, CINAHL and Web of Science were searched from inception until January 2025. Studies that included acutely admitted patients aged 65 years or older and reported changes in at least one measure of sarcopenia during hospitalisation were included. Barthel Index was also included. A random-effects meta-analysis was undertaken.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-five eligible studies were included, with a participant mean age of 82.2 years (<i>n</i> = 14 919 participants). Our meta-analysis showed grip strength and chair-to-stand performance to significantly increase during hospitalisation (standard mean difference [SMD] = 0.06, 95% confidence interval [CI]: 0.00; 0.13, <i>I</i><sup>2</sup> = 3%, <i>p</i> = 0.05 and SMD = 0.23, 95% CI: 0.13; 0.33, <i>I</i><sup>2</sup> = 0%, <i>p</i> < 0.01, respectively). No physical performance measure showed a significant change. Muscle mass showed no change when measured by bioelectrical impedance analysis (SMD = 0.01, 95% CI: −0.09; 0.08, <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.86). There were insufficient studies using MRI (<i>n</i> = 2) or DEXA (<i>n</i> = 1) to perform a meta-analysis. Individual studies showed a significant decrease in mid-thigh muscle area (cm<sup>2</sup>) by MRI (mean difference [MD] = −3.9, <i>p</i> < 0.01) and a significant decrease in leg lean mass (kg) by DEXA (MD = −0.16, <i>p</i> < 0.05). Barthel Index score significantly increased from admission to discharge (SMD = 0.26, 95% CI: 0.06; 0.46, <i>I</i><sup>2</sup> = 98.0%, <i>p</i> = 0.01) but significantly decreased from preadmission to discharge (SMD = −0.66, 95% CI: −0.92; −0.39, <i>I</i><sup>2</sup> = 97.5%, <i>p</i> < 0.001). Both age and hospital length of stay had no effect on grip strength (<i>p</i> = 0.615 and <i>p</i> = 0.096) or Barthel Index (<i>p</i> = 0.835 and <i>p</i> = 0.279).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review has shown that grip strength improves during hospitalisation and decreases in muscle mass are observed when measured using MRI or DEXA. Muscle strength and physical performance assessed on admission are poor indicators of baseli","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145887788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rohini Bhadra, Debbie Gach, Frits H. M. van Osch, Joop P. van den Bergh, Sucharita Sambashivaiah, Annemie M. W. J. Schols, Rosanne J. H. C. G. Beijers
Background
Muscle mass is an important determinant of clinical outcome in chronic diseases as well as in acute infectious diseases such as COVID-19. Both dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) imaging are utilized to quantify muscle. The objective of this study was to assess the agreement between CT segmental analysis of muscle and whole-body muscle mass from DXA.
Methods
A prospective observational study was carried out among COVID-19 survivors at least 1 year after the infection. The participants underwent a comprehensive multidimensional health assessment, including DXA and an extended chest CT. Lean mass (LM) and appendicular skeletal muscle mass (SMM) were derived from DXA, and pectoralis, L1 and L3 muscle cross-sectional area (CSA) were assessed using Slice-O-Matic software version 5.0 from the CT scans. Agreement between the two methods was assessed using Pearson correlation and Bland–Altman plots.
Results
One hundred thirty COVID-19 survivors (age 60.8 ± 13.1 years, female % 31.5, BMI 29.9 ± 5.2 kg/m2) were included in the analysis. 83.9% of the participants were obese or overweight. Muscle CSA at L1 and L3 had a strong positive correlation with DXA LM and SMM (L1: r = 0.866 and r = 0.853 for LM and SMM, respectively; L3: r = 0.845 and r = 0.845, p < 0.001). Bland–Altman plots showed good agreement between the two methods. CT pectoralis showed a moderate correlation with DXA LM and SMM (r = 0.659 and r = 0.684, respectively, p < 0.001).
Conclusions
Muscle CSA at L1 and L3 from CT scans is strongly correlated, and pectoralis muscle CSA is moderately correlated with whole-body muscle mass measurement from DXA scans among COVID-19 survivors.
肌肉质量是慢性疾病以及COVID-19等急性传染病临床结果的重要决定因素。双能x线吸收仪（DXA）和计算机断层扫描（CT）成像用于量化肌肉。本研究的目的是评估肌肉的CT分段分析和DXA的全身肌肉质量之间的一致性。方法对感染后至少1年的COVID-19幸存者进行前瞻性观察研究。参与者接受了全面的多维健康评估，包括DXA和扩展胸部CT。瘦肉质量（LM）和阑尾骨骼肌质量（SMM）由DXA计算，胸肌、L1和L3肌肉横截面积（CSA）使用Slice-O-Matic软件5.0版本从CT扫描中评估。使用Pearson相关性和Bland-Altman图评估两种方法之间的一致性。结果纳入新冠肺炎幸存者130例（年龄60.8±13.1岁，女性31.5 %,BMI 29.9±5.2 kg/m2）。83.9%的参与者肥胖或超重。L1和L3肌肉CSA与DXA LM和SMM有很强的正相关（L1: LM和SMM分别r = 0.866和r = 0.853; L3: r = 0.845和r = 0.845, p < 0.001）。Bland-Altman图显示了两种方法之间的良好一致性。CT显示胸肌与DXA LM、SMM有中度相关性（r = 0.659、r = 0.684, p < 0.001）。结论在COVID-19幸存者中，CT扫描L1和L3的肌肉CSA与DXA扫描的全身肌肉质量测量值有很强的相关性，胸肌CSA与DXA扫描的全身肌肉质量测量值有中度相关性。
{"title":"Comparison of Computed Tomography Derived Muscle Cross-Sectional Area With Dual-Energy X-Ray Absorptiometry Derived Whole-Body Muscle Mass in COVID-19 Survivors","authors":"Rohini Bhadra, Debbie Gach, Frits H. M. van Osch, Joop P. van den Bergh, Sucharita Sambashivaiah, Annemie M. W. J. Schols, Rosanne J. H. C. G. Beijers","doi":"10.1002/rco2.70022","DOIUrl":"https://doi.org/10.1002/rco2.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle mass is an important determinant of clinical outcome in chronic diseases as well as in acute infectious diseases such as COVID-19. Both dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) imaging are utilized to quantify muscle. The objective of this study was to assess the agreement between CT segmental analysis of muscle and whole-body muscle mass from DXA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective observational study was carried out among COVID-19 survivors at least 1 year after the infection. The participants underwent a comprehensive multidimensional health assessment, including DXA and an extended chest CT. Lean mass (LM) and appendicular skeletal muscle mass (SMM) were derived from DXA, and pectoralis, L1 and L3 muscle cross-sectional area (CSA) were assessed using Slice-O-Matic software version 5.0 from the CT scans. Agreement between the two methods was assessed using Pearson correlation and Bland–Altman plots.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred thirty COVID-19 survivors (age 60.8 ± 13.1 years, female % 31.5, BMI 29.9 ± 5.2 kg/m<sup>2</sup>) were included in the analysis. 83.9% of the participants were obese or overweight. Muscle CSA at L1 and L3 had a strong positive correlation with DXA LM and SMM (L1: <i>r</i> = 0.866 and <i>r</i> = 0.853 for LM and SMM, respectively; L3: <i>r</i> = 0.845 and <i>r</i> = 0.845, <i>p</i> < 0.001). Bland–Altman plots showed good agreement between the two methods. CT pectoralis showed a moderate correlation with DXA LM and SMM (<i>r</i> = 0.659 and <i>r</i> = 0.684, respectively, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Muscle CSA at L1 and L3 from CT scans is strongly correlated, and pectoralis muscle CSA is moderately correlated with whole-body muscle mass measurement from DXA scans among COVID-19 survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Preoperative evaluation of sarcopenia and nutritional status is a crucial prognostic factor in patients with gastrointestinal malignancies (GIM). Whole-body phase angle (Ph A), measured via bioelectrical impedance analysis (BIA), reflects cellular health and nutritional condition, and has gained attention as a potential prognostic marker.
Methods
This study included 149 patients who underwent surgery for GIM at our department between April 2024 and May 2025. Sarcopenia was assessed using skeletal muscle index (SMI; men: < 7.0, women: < 5.7 kg m2) derived from BIA, and those meeting the criteria were classified as ‘presumed sarcopenia (P-sarcopenia)’. Ph A values were also obtained using BIA, and skeletal muscle volume was measured using SYNAPSE VINCENT to determine the volume of large psoas muscle (PV).
Results
Among the 149 patients, 58 (38.9%) were diagnosed with P-sarcopenia, the breakdown being 31 males (53.4%) and 27 females (46.6%). The median age was 76 years (range: 53–89). Multivariate analysis revealed that low Ph A (odds ratio: 0.537, p < 0.04) and low PV (odds ratio: 0.992, p < 0.007) were significant risk factors for P-sarcopenia. These findings suggest that patients with P-sarcopenia tend to have lower Ph A and PV values.
Conclusions
Patients with GIM who present with P-sarcopenia are more likely to exhibit reduced Ph A and PV, indicating compromised cellular and nutritional status. Ph A, as a non-invasive and easily obtainable parameter via BIA, may serve as a useful screening tool for identifying P-sarcopenia in preoperative settings.
{"title":"Association of Sarcopenia With Phase Angle and Urinary Titin Fragment in Patients With Gastrointestinal Malignancies","authors":"Mitsugi Shimoda, Masahiro Shiihara, Mitsuru Watanabe, Ryoichi Miyamoto, Jiro Shimazaki, Shuji Suzuki","doi":"10.1002/rco2.70025","DOIUrl":"https://doi.org/10.1002/rco2.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preoperative evaluation of sarcopenia and nutritional status is a crucial prognostic factor in patients with gastrointestinal malignancies (GIM). Whole-body phase angle (Ph A), measured via bioelectrical impedance analysis (BIA), reflects cellular health and nutritional condition, and has gained attention as a potential prognostic marker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 149 patients who underwent surgery for GIM at our department between April 2024 and May 2025. Sarcopenia was assessed using skeletal muscle index (SMI; men: < 7.0, women: < 5.7 kg m<sup>2</sup>) derived from BIA, and those meeting the criteria were classified as ‘presumed sarcopenia (P-sarcopenia)’. Ph A values were also obtained using BIA, and skeletal muscle volume was measured using SYNAPSE VINCENT to determine the volume of large psoas muscle (PV).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 149 patients, 58 (38.9%) were diagnosed with P-sarcopenia, the breakdown being 31 males (53.4%) and 27 females (46.6%). The median age was 76 years (range: 53–89). Multivariate analysis revealed that low Ph A (odds ratio: 0.537, <i>p</i> < 0.04) and low PV (odds ratio: 0.992, <i>p</i> < 0.007) were significant risk factors for P-sarcopenia. These findings suggest that patients with P-sarcopenia tend to have lower Ph A and PV values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with GIM who present with P-sarcopenia are more likely to exhibit reduced Ph A and PV, indicating compromised cellular and nutritional status. Ph A, as a non-invasive and easily obtainable parameter via BIA, may serve as a useful screening tool for identifying P-sarcopenia in preoperative settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caleb P. Calaway, Ana Raquel Calzada, Michel Huyghe, Colten Brown, Humzah Ali, Kylie Martinez, Bryan Mann, Ihtsham Haq, Joseph F. Signorile
<div> <section> <h3> Background</h3> <p>High-speed resistance training has been shown to be a viable intervention for reducing neuromuscular symptoms in older persons with Parkinson's disease. Velocity-based training, a recently developed resistance training modality, utilizes velocity rather than load to dictate progressions. No study has examined the effects of this training method on muscle structure in Parkinson's patients.</p> </section> <section> <h3> Methods</h3> <p>Sixteen older adults with Parkinson's disease (Hoehn and Yahr Stages 1–3) were randomly assigned to a 10% (<i>n</i> = 7, 6 males, 1 female) or 30% (<i>n</i> = 9, 6 males, 3 females) velocity loss threshold protocol twice weekly for 12 weeks of velocity-based training. Changes in ultrasound measures including muscle thickness, echo intensity, pennation angle, shear wave elastography, and performance measurements including specific force and power of the left and right rectus femoris and vastus lateralis were analysed before and after the intervention period.</p> </section> <section> <h3> Results</h3> <p>Significant improvements were seen for the sample in muscle thickness for the right (MDiff ± SE = 0.19 ± 0.05 cm; <i>p</i> = 0.003) and left (0.20 ± 0.09 cm; <i>p</i> = 0.033) rectus femoris and the right (0.14 ± 0.06 cm; <i>p</i> = 0.04) and left (0.19 ± 0.07 cm; <i>p</i> = 0.018) vastus lateralis. For echo intensity, there were significant improvements for the right rectus femoris (−3.37 ± 1.29 units; <i>p</i> = 0.002) and the left vastus lateralis (−7.11 ± 2.68 units; <i>p</i> = 0.019); however, improvements in the left (<i>p</i> = 0.033) and right (<i>p</i> < 0.001) vastus lateralis were seen only by the 30% velocity loss threshold group. Significant increases in pennation angle were detected in the right rectus femoris (2.47° ± 0.84°; <i>p</i> = 0.011) and reductions in shear wave elastography for the left rectus femoris (−3.33 ± 1.29 kPa; <i>p</i> = 0.013) of the sample. For specific power, significant improvements were seen for the right (0.02 ± 0.01 W·cm<sup>3</sup>; <i>p</i> = 0.040) and left (0.04 ± 0.02 W·cm<sup>3</sup>; <i>p</i> = 0.047) rectus femoris muscles for both groups.</p> </section> <section> <h3> Conclusions</h3> <p>Results indicate that 12 weeks of velocity-based training can produce positive changes in muscle morphology and neuromuscular performance of the lower limbs for individuals with Parkinson's disease. Furthermore, using a 30% velocity loss threshold is more effective than using a 10% velocity loss threshold.</p> <p><
高速阻力训练已被证明是减轻老年帕金森病患者神经肌肉症状的一种可行的干预措施。以速度为基础的训练，是最近发展起来的一种阻力训练方式，利用速度而不是负荷来决定进步。目前还没有研究检验这种训练方法对帕金森病患者肌肉结构的影响。方法将16例老年帕金森病患者（Hoehn和Yahr阶段1 - 3）随机分为10% （n = 7, 6男性，1女性）或30% （n = 9, 6男性，3女性）速度损失阈值方案，每周2次，为期12周的速度训练。分析干预前后肌肉厚度、回声强度、穿刺角度、横波弹性成像等超声指标的变化，以及左右股直肌和股外侧肌比力和功率等性能指标的变化。结果右股直肌（MDiff±SE = 0.19±0.05 cm, p = 0.003）、左股直肌（0.20±0.09 cm, p = 0.033）、右股外侧肌（0.14±0.06 cm, p = 0.04）、左股外侧肌（0.19±0.07 cm, p = 0.018）的肌肉厚度均有显著改善。回声强度方面，右侧股直肌（- 3.37±1.29个单位，p = 0.002）和左侧股外侧肌（- 7.11±2.68个单位，p = 0.019）有显著改善；然而，只有30%速度损失阈值组的左股外侧肌（p = 0.033）和右股外侧肌（p < 0.001）有所改善。右侧股直肌的穿刺角显著增加（2.47°±0.84°，p = 0.011），左侧股直肌的横波弹性图显著减少（- 3.33±1.29 kPa, p = 0.013）。在比功率方面，两组右股直肌（0.02±0.01 W·cm3, p = 0.040）和左股直肌（0.04±0.02 W·cm3, p = 0.047）均有显著改善。结果表明，12周的速度训练可以对帕金森病患者的下肢肌肉形态和神经肌肉性能产生积极的影响。此外，使用30%的速度损失阈值比使用10%的速度损失阈值更有效。试验注册：20220489
{"title":"Velocity-Based-Training Induces Positive Changes in Muscle Morphology in Parkinson's Disease Patients: A Pilot Study","authors":"Caleb P. Calaway, Ana Raquel Calzada, Michel Huyghe, Colten Brown, Humzah Ali, Kylie Martinez, Bryan Mann, Ihtsham Haq, Joseph F. Signorile","doi":"10.1002/rco2.70023","DOIUrl":"https://doi.org/10.1002/rco2.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-speed resistance training has been shown to be a viable intervention for reducing neuromuscular symptoms in older persons with Parkinson's disease. Velocity-based training, a recently developed resistance training modality, utilizes velocity rather than load to dictate progressions. No study has examined the effects of this training method on muscle structure in Parkinson's patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixteen older adults with Parkinson's disease (Hoehn and Yahr Stages 1–3) were randomly assigned to a 10% (<i>n</i> = 7, 6 males, 1 female) or 30% (<i>n</i> = 9, 6 males, 3 females) velocity loss threshold protocol twice weekly for 12 weeks of velocity-based training. Changes in ultrasound measures including muscle thickness, echo intensity, pennation angle, shear wave elastography, and performance measurements including specific force and power of the left and right rectus femoris and vastus lateralis were analysed before and after the intervention period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant improvements were seen for the sample in muscle thickness for the right (MDiff ± SE = 0.19 ± 0.05 cm; <i>p</i> = 0.003) and left (0.20 ± 0.09 cm; <i>p</i> = 0.033) rectus femoris and the right (0.14 ± 0.06 cm; <i>p</i> = 0.04) and left (0.19 ± 0.07 cm; <i>p</i> = 0.018) vastus lateralis. For echo intensity, there were significant improvements for the right rectus femoris (−3.37 ± 1.29 units; <i>p</i> = 0.002) and the left vastus lateralis (−7.11 ± 2.68 units; <i>p</i> = 0.019); however, improvements in the left (<i>p</i> = 0.033) and right (<i>p</i> < 0.001) vastus lateralis were seen only by the 30% velocity loss threshold group. Significant increases in pennation angle were detected in the right rectus femoris (2.47° ± 0.84°; <i>p</i> = 0.011) and reductions in shear wave elastography for the left rectus femoris (−3.33 ± 1.29 kPa; <i>p</i> = 0.013) of the sample. For specific power, significant improvements were seen for the right (0.02 ± 0.01 W·cm<sup>3</sup>; <i>p</i> = 0.040) and left (0.04 ± 0.02 W·cm<sup>3</sup>; <i>p</i> = 0.047) rectus femoris muscles for both groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Results indicate that 12 weeks of velocity-based training can produce positive changes in muscle morphology and neuromuscular performance of the lower limbs for individuals with Parkinson's disease. Furthermore, using a 30% velocity loss threshold is more effective than using a 10% velocity loss threshold.</p>\u0000 \u0000 <p><","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>Muscle weakness with age precedes muscle mass loss, and muscle quality is an issue in sarcopenia. Muscle tissue fibrosis progresses with age, with an increasing proportion of connective tissue containing collagen fibres. Increased fibrosis reduces the efficiency of force transmission during muscle contraction, leading to decreased muscle tension and overall performance. However, few studies have focused specifically on this condition and examined its treatment and effects. Using senescence-accelerated mouse-prone 8 (SAMP8) models, we aimed to clarify the effects of stretch stimulation on fibrosis and examine muscle function, histological changes in fibrosis and changes in fibrosis-related genes.</p> </section> <section> <h3> Methods</h3> <p>The right side of the gastrocnemius muscle of 8-month-old SAMP8 was the stretch group and the left side the control group (<i>n</i> = 8/group). The intervention was performed 15 times/min, 15 min/day and 5 days/week for 2 weeks. Muscle wet weight (MWW), ankle joint range of motion and passive/active tension were measured to evaluate muscle function. For histological analysis, muscle fibre cross-sectional area (CSA) and collagen content were calculated using haematoxylin and eosin and picrosirius-red staining, respectively. For molecular biological analysis, mRNA expression levels of fibrosis-related genes, transforming growth factor-β, α-smooth muscle actin (SMA), and collagen types I and III were measured using quantitative polymerase chain reaction.</p> </section> <section> <h3> Results</h3> <p>There was no significant difference in body weight and ankle joint's range of motion before and after the intervention. MWW after the intervention was higher in the stretch group (control group, 0.13 ± 0.01 g vs. stretch group, 0.14 ± 0.01 g; <i>p</i> < 0.05). No significant difference occurred in passive tension between groups; active tension was higher in the stretch group (control group, 2.98 ± 0.53 N/g vs. stretch group, 3.67 ± 0.52 N/g; <i>p</i> < 0.05). Histological findings showed a significantly higher CSA (control group, 2065.21 ± 93.98 μm<sup>2</sup> vs. stretch group, 2571.15 ± 187.12 μm<sup>2</sup>; <i>p</i> < 0.05) and a significantly lower collagen content in the stretch group (control group, 1.28 ± 0.47% vs. stretch group, 0.53 ± 0.14%; <i>p</i> < 0.05). Thickening of the perimysium and endomysium was lower in the stretch group. Molecular biological findings showed a significant decrease in the expression levels of fibrosis-related genes, including α-SMA (control group, 1 ± 0.49 vs. stretch group, 0.30 ± 0.16; <i>p</i> < 0.05) and collagen type III (c
背景随着年龄的增长肌肉无力先于肌肉质量的减少，肌肉质量是肌肉减少症的一个问题。肌肉组织纤维化随着年龄的增长而发展，含有胶原纤维的结缔组织的比例增加。纤维化的增加降低了肌肉收缩过程中力传递的效率，导致肌肉张力和整体表现下降。然而，很少有研究专门关注这种情况，并检查其治疗和影响。使用衰老加速小鼠8 （SAMP8）模型，我们旨在阐明拉伸刺激对纤维化的影响，并检查肌肉功能、纤维化组织学变化和纤维化相关基因的变化。方法8月龄SAMP8腓肠肌右侧为拉伸组，左侧为对照组（n = 8/组）。干预15次/分钟，15分钟/天，5天/周，共2周。测量肌肉湿重（MWW）、踝关节活动范围和被动/主动张力来评估肌肉功能。进行组织学分析时，分别采用苏木精、伊红和小红染色法计算肌纤维横截面积（CSA）和胶原蛋白含量。在分子生物学分析方面，采用定量聚合酶链反应法测定了纤维化相关基因、转化生长因子-β、α-平滑肌肌动蛋白（SMA）和ⅰ型和ⅲ型胶原蛋白的mRNA表达水平。结果干预前后患者体重、踝关节活动度无显著差异。拉伸组干预后MWW较高（对照组0.13±0.01 g，拉伸组0.14±0.01 g; p < 0.05）。两组间被动张力无显著差异；张力组主动张力明显高于张力组（对照组为2.98±0.53 N/g，张力组为3.67±0.52 N/g; p < 0.05）。组织学结果显示，拉伸组CSA显著增高（对照组，2065.21±93.98 μm2比拉伸组高，2571.15±187.12 μm2; p < 0.05），胶原含量显著降低（对照组，1.28±0.47%比拉伸组高，0.53±0.14%;p < 0.05）。牵张组肌周和肌内膜增厚较低。分子生物学结果显示，纤维化相关基因α-SMA（对照组，与拉伸组相比，1±0.49,0.30±0.16;p < 0.05）和III型胶原（对照组，与拉伸组相比，1±0.39,0.37±0.23;p < 0.05）的表达水平显著降低。结论拉伸干预SAMP8降低了一些纤维化相关基因的表达，可能导致骨骼肌胶原增殖减少和活性张力增加。
{"title":"Effect of Stretching on Skeletal Muscle Fibrosis in Sarcopenia","authors":"Daiki Nohara, Momoko Nagai-Tanima, Shion Masuda, Misa Toyota, Ryo Nakahara, Kazuhiro Hayashi, Tomoki Aoyama","doi":"10.1002/rco2.70021","DOIUrl":"https://doi.org/10.1002/rco2.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle weakness with age precedes muscle mass loss, and muscle quality is an issue in sarcopenia. Muscle tissue fibrosis progresses with age, with an increasing proportion of connective tissue containing collagen fibres. Increased fibrosis reduces the efficiency of force transmission during muscle contraction, leading to decreased muscle tension and overall performance. However, few studies have focused specifically on this condition and examined its treatment and effects. Using senescence-accelerated mouse-prone 8 (SAMP8) models, we aimed to clarify the effects of stretch stimulation on fibrosis and examine muscle function, histological changes in fibrosis and changes in fibrosis-related genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The right side of the gastrocnemius muscle of 8-month-old SAMP8 was the stretch group and the left side the control group (<i>n</i> = 8/group). The intervention was performed 15 times/min, 15 min/day and 5 days/week for 2 weeks. Muscle wet weight (MWW), ankle joint range of motion and passive/active tension were measured to evaluate muscle function. For histological analysis, muscle fibre cross-sectional area (CSA) and collagen content were calculated using haematoxylin and eosin and picrosirius-red staining, respectively. For molecular biological analysis, mRNA expression levels of fibrosis-related genes, transforming growth factor-β, α-smooth muscle actin (SMA), and collagen types I and III were measured using quantitative polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was no significant difference in body weight and ankle joint's range of motion before and after the intervention. MWW after the intervention was higher in the stretch group (control group, 0.13 ± 0.01 g vs. stretch group, 0.14 ± 0.01 g; <i>p</i> < 0.05). No significant difference occurred in passive tension between groups; active tension was higher in the stretch group (control group, 2.98 ± 0.53 N/g vs. stretch group, 3.67 ± 0.52 N/g; <i>p</i> < 0.05). Histological findings showed a significantly higher CSA (control group, 2065.21 ± 93.98 μm<sup>2</sup> vs. stretch group, 2571.15 ± 187.12 μm<sup>2</sup>; <i>p</i> < 0.05) and a significantly lower collagen content in the stretch group (control group, 1.28 ± 0.47% vs. stretch group, 0.53 ± 0.14%; <i>p</i> < 0.05). Thickening of the perimysium and endomysium was lower in the stretch group. Molecular biological findings showed a significant decrease in the expression levels of fibrosis-related genes, including α-SMA (control group, 1 ± 0.49 vs. stretch group, 0.30 ± 0.16; <i>p</i> < 0.05) and collagen type III (c","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>Cancer cachexia is a multifactorial metabolic syndrome characterized by anorexia and the progressive loss of skeletal muscle and adipose tissue, severely impairing quality of life, shortening survival and reducing treatment efficacy in cancer patients. The development of effective therapies has been hampered by the lack of preclinical models that faithfully replicate the clinical features and underlying mechanisms of cachexia. This study aimed to establish a novel murine model of cancer cachexia using subcutaneous implantation of renal carcinoma (RenCa) cells that align with clinical diagnostic criteria.</p> </section> <section> <h3> Methods</h3> <p>On Day 0, 8-week-old male BALB/c mice were anaesthetised and subcutaneously injected with murine RenCa cells or vehicle (control). A subset of mice was subjected to pair-feeding with RenCa-bearing mice, while another subset underwent subdiaphragmatic vagotomy (SDV) 2 weeks before cell implantation. Plasma levels of acyl-ghrelin and insulin-like growth factor-1 (IGF-1) were measured by ELISA. The gastrocnemius muscle was analysed for gene and protein expression related to atrophy and energy metabolism using quantitative RT-PCR and Western blotting, respectively, and for metabolic alterations using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS).</p> </section> <section> <h3> Results</h3> <p>Mice bearing RenCa tumours exhibited progressive cachexia. By Day 30, compared to controls, RenCa-bearing mice had significantly reduced tumour-free body weight (20.3 vs. 26.1 g), daily food intake (1.8 vs. 3.0 g/day), gastrocnemius muscle mass (112.1 vs. 140.7 mg) and epididymal fat mass (18.6 vs. 307.3 mg; all <i>p</i> < 0.01). Grip strength normalized to body mass remained unchanged even on Day 30. The pair-feeding experiment revealed that anorexia largely contributed to the onset of cachexic-like symptoms. SDV further exacerbated gastrocnemius atrophy (<i>p</i> < 0.05), implicating vagal signalling in the pathogenesis of cachexia, other than anorexia. Muscle expression of <i>Trim63</i> and <i>Fbxo32</i> peaked on Day 20, showing 5.5- and 4.4-fold increases compared with controls, respectively. The expression of <i>Ctsl</i> and <i>4ebp1</i> increased on Day 7 and remained elevated until Day 20. Metabolomic analyses revealed impaired glutathione and Akt-mediated glucose metabolism. Plasma acyl-ghrelin levels were elevated in RenCa-bearing mice (38.5–49.1 pg/mL) compared to controls (33.3–37.9 pg/mL) from Day 14 to Day 30, while IGF-1 levels were significantly reduced on Day 14 (94.6 vs. 220.2 ng/mL; <i>p</i> < 0.05).</p> </section
癌症恶病质是一种多因素代谢综合征，以厌食和骨骼肌和脂肪组织的进行性损失为特征，严重影响癌症患者的生活质量，缩短生存期，降低治疗效果。由于缺乏临床前模型来忠实地复制恶病质的临床特征和潜在机制，有效治疗方法的发展受到阻碍。本研究旨在建立符合临床诊断标准的肾癌（RenCa）细胞皮下植入的新型小鼠癌症恶病质模型。方法在第0天麻醉8周龄雄性BALB/c小鼠，皮下注射小鼠RenCa细胞或对照。一组小鼠与含renca小鼠配对喂养，另一组小鼠在细胞植入前2周进行膈下迷走神经切开术（SDV）。ELISA法检测血浆中酰基生长素和胰岛素样生长因子-1 （IGF-1）水平。使用定量RT-PCR和Western blotting分别分析腓肠肌萎缩和能量代谢相关的基因和蛋白质表达，并使用毛细管电泳飞行时间质谱（CE-TOF-MS）分析代谢变化。结果RenCa肿瘤小鼠表现出进行性恶病质。到第30天，与对照组相比，renca小鼠的无瘤体重（20.3比26.1 g）、每日食物摄入量（1.8比3.0 g/d）、腓肠肌质量（112.1比140.7 mg）和附睾脂肪质量（18.6比307.3 mg，均p <； 0.01）显著减少。握力与体重的比值即使在第30天也保持不变。配对喂养实验显示，厌食症在很大程度上导致了恶病质样症状的出现。SDV进一步加重了肠肌萎缩（p < 0.05），暗示迷走神经信号在恶病质的发病机制中，而不是厌食症。Trim63和Fbxo32的肌肉表达在第20天达到峰值，分别比对照组增加5.5倍和4.4倍。Ctsl和4ebp1的表达在第7天升高，并持续升高至第20天。代谢组学分析显示谷胱甘肽和akt介导的葡萄糖代谢受损。与对照组（33.3-37.9 pg/mL）相比，renca小鼠血浆中酰胃饥饿素水平在第14天至第30天升高（38.5-49.1 pg/mL），而IGF-1水平在第14天显著降低（94.6 vs. 220.2 ng/mL; p < 0.05）。我们建立了renca诱导的癌症恶病质小鼠模型，该模型概括了关键的临床特征，包括进行性厌食症、体重减轻、肌肉萎缩和ghrelin-IGF-1信号改变，为机制研究和治疗开发提供了有价值的工具。
{"title":"A Novel Mouse Model Recapitulating the Clinical Progression of Cancer Cachexia Induced by Renal Carcinoma Cells","authors":"Miaki Uzu, Anzu Aoyama, Takumi Kobayashi, Mayuka Morita, Rumi Murayama, Kenji Hashimoto, Hiroyuki Nakamura","doi":"10.1002/rco2.70018","DOIUrl":"https://doi.org/10.1002/rco2.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia is a multifactorial metabolic syndrome characterized by anorexia and the progressive loss of skeletal muscle and adipose tissue, severely impairing quality of life, shortening survival and reducing treatment efficacy in cancer patients. The development of effective therapies has been hampered by the lack of preclinical models that faithfully replicate the clinical features and underlying mechanisms of cachexia. This study aimed to establish a novel murine model of cancer cachexia using subcutaneous implantation of renal carcinoma (RenCa) cells that align with clinical diagnostic criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>On Day 0, 8-week-old male BALB/c mice were anaesthetised and subcutaneously injected with murine RenCa cells or vehicle (control). A subset of mice was subjected to pair-feeding with RenCa-bearing mice, while another subset underwent subdiaphragmatic vagotomy (SDV) 2 weeks before cell implantation. Plasma levels of acyl-ghrelin and insulin-like growth factor-1 (IGF-1) were measured by ELISA. The gastrocnemius muscle was analysed for gene and protein expression related to atrophy and energy metabolism using quantitative RT-PCR and Western blotting, respectively, and for metabolic alterations using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mice bearing RenCa tumours exhibited progressive cachexia. By Day 30, compared to controls, RenCa-bearing mice had significantly reduced tumour-free body weight (20.3 vs. 26.1 g), daily food intake (1.8 vs. 3.0 g/day), gastrocnemius muscle mass (112.1 vs. 140.7 mg) and epididymal fat mass (18.6 vs. 307.3 mg; all <i>p</i> < 0.01). Grip strength normalized to body mass remained unchanged even on Day 30. The pair-feeding experiment revealed that anorexia largely contributed to the onset of cachexic-like symptoms. SDV further exacerbated gastrocnemius atrophy (<i>p</i> < 0.05), implicating vagal signalling in the pathogenesis of cachexia, other than anorexia. Muscle expression of <i>Trim63</i> and <i>Fbxo32</i> peaked on Day 20, showing 5.5- and 4.4-fold increases compared with controls, respectively. The expression of <i>Ctsl</i> and <i>4ebp1</i> increased on Day 7 and remained elevated until Day 20. Metabolomic analyses revealed impaired glutathione and Akt-mediated glucose metabolism. Plasma acyl-ghrelin levels were elevated in RenCa-bearing mice (38.5–49.1 pg/mL) compared to controls (33.3–37.9 pg/mL) from Day 14 to Day 30, while IGF-1 levels were significantly reduced on Day 14 (94.6 vs. 220.2 ng/mL; <i>p</i> < 0.05).</p>\u0000 </section","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>In the current issue of <i>JCSM Communications</i>, a systematic review and meta-analysis [<span>1</span>] investigated the impact of resistance exercise training (RET) in prehabilitation protocols implemented in the management of colorectal cancer (CRC) patients. The findings suggest that, despite the limited sample size, heterogeneity and risk of bias, exercise improves physical function, supporting the inclusion of RET for prehabilitation in CRC patients scheduled for surgery.</p><p>This work highlights the importance of supportive oncology interventions in the management of cancer patients throughout the whole cancer continuum. The final aim is to be able to significantly impact on patients' quality of life and survival, beyond the outcome of medical and/or surgical cancer treatment.</p><p>According to a recent scoping review [<span>2</span>], prehabilitation is defined as a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition and psychological strategies that aim to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes (e.g., shorter hospital stay, reduced complications) and facilitate recovery. It is remarkable that most of such objectives are shared with anti-cancer cachexia interventions, primarily aiming to counteract body and lean mass wasting and to improve muscle strength, with a potential impact on prehabilitation targets, including postoperative morbidity and recovery.</p><p>Prehabilitation programmes can be very heterogeneous [<span>3</span>] in terms of setting (e.g., home and hospital-based), duration (e.g., 3–4 weeks, months) and components. Most of the interventions typically include (1) a personalized exercise programme combining endurance and resistance training and (2) a nutritional intervention with a balanced macronutrient diet and protein oral nutritional supplements. Both components aim to improve cardiorespiratory fitness, body composition and nutritional status to better tolerate the stress response and disability resulting from surgery and/or other cancer-related treatments.</p><p>It is thus evident that prehabilitation and cachexia research share the focus on sarcopenia, malnutrition, functional capacity and quality of life. Such common interests open an opportunity for merging knowledge and resources, with the potential to cross-fertilize the respective research fields, eventually providing an acceleration in discoveries and new therapy optimization. As an example, with muscle wasting/sarcopenia well characterized during cancer cachexia and current clinical trials ongoing to prevent it, the same drugs may be tested for preventing sarcopenia during cancer patient prehabilitation. Along the same lines, drugs that improve the nutritional status in cachectic individuals, such as ghrelin analogues or GDF-15 blockers, may be efficiently adopted during prehabilitation interventions
{"title":"Prehabilitation Meets Cancer Cachexia: Current Challenges and Opportunities","authors":"Nicolò Pecorelli, Fabio Penna","doi":"10.1002/rco2.70019","DOIUrl":"https://doi.org/10.1002/rco2.70019","url":null,"abstract":"<p>In the current issue of <i>JCSM Communications</i>, a systematic review and meta-analysis [<span>1</span>] investigated the impact of resistance exercise training (RET) in prehabilitation protocols implemented in the management of colorectal cancer (CRC) patients. The findings suggest that, despite the limited sample size, heterogeneity and risk of bias, exercise improves physical function, supporting the inclusion of RET for prehabilitation in CRC patients scheduled for surgery.</p><p>This work highlights the importance of supportive oncology interventions in the management of cancer patients throughout the whole cancer continuum. The final aim is to be able to significantly impact on patients' quality of life and survival, beyond the outcome of medical and/or surgical cancer treatment.</p><p>According to a recent scoping review [<span>2</span>], prehabilitation is defined as a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition and psychological strategies that aim to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes (e.g., shorter hospital stay, reduced complications) and facilitate recovery. It is remarkable that most of such objectives are shared with anti-cancer cachexia interventions, primarily aiming to counteract body and lean mass wasting and to improve muscle strength, with a potential impact on prehabilitation targets, including postoperative morbidity and recovery.</p><p>Prehabilitation programmes can be very heterogeneous [<span>3</span>] in terms of setting (e.g., home and hospital-based), duration (e.g., 3–4 weeks, months) and components. Most of the interventions typically include (1) a personalized exercise programme combining endurance and resistance training and (2) a nutritional intervention with a balanced macronutrient diet and protein oral nutritional supplements. Both components aim to improve cardiorespiratory fitness, body composition and nutritional status to better tolerate the stress response and disability resulting from surgery and/or other cancer-related treatments.</p><p>It is thus evident that prehabilitation and cachexia research share the focus on sarcopenia, malnutrition, functional capacity and quality of life. Such common interests open an opportunity for merging knowledge and resources, with the potential to cross-fertilize the respective research fields, eventually providing an acceleration in discoveries and new therapy optimization. As an example, with muscle wasting/sarcopenia well characterized during cancer cachexia and current clinical trials ongoing to prevent it, the same drugs may be tested for preventing sarcopenia during cancer patient prehabilitation. Along the same lines, drugs that improve the nutritional status in cachectic individuals, such as ghrelin analogues or GDF-15 blockers, may be efficiently adopted during prehabilitation interventions ","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>Muscle atrophy is critical to cognitive decline, as evidenced in previous studies which showed that disuse-induced skeletal muscle atrophy in the hind limbs accelerated early cognitive decline in young Alzheimer's model 5XFAD mice and nontransgenic young mice. As physical activity is challenging for individuals with muscle loss due to aging or immobilisation, effective medications are needed to prevent cast immobilisation–induced cognitive decline. Rutin, a candidate medication for preventing muscle loss and cognitive decline, has numerous biological effects but is limited by its low bioavailability owing to water insolubility. EubioQuercetin (ws Rutin), a highly absorbable Rutin formula, offers over 2000-fold improved solubility. This study investigated whether oral water-soluble Rutin (ws Rutin) treatment prevents cast immobilisation–induced memory dysfunction in young mice and explored its underlying mechanism.</p> </section> <section> <h3> Methods</h3> <p>Healthy young male ddY mice (10 weeks old) were used. Tissue distribution of Rutin was determined using LC-MS/MS at 0.5, 3, 6 and 16 h after oral administration of ws Rutin or conventional Rutin. Muscle atrophy was induced via bilateral hindlimb immobilisation by placing them in casts for 17 days. Cognitive function was evaluated using an object recognition test. RNA-seq was used to comprehensively analyse mRNA expression in the hippocampus and triceps surae. Expression levels of candidate molecules, affected by immobilisation and ws Rutin treatment, were confirmed using immunohistochemistry and Western blotting. Cultured hippocampal neurons and myocytes were treated with ws Rutin or Rutin, and parameters such as Klotho expression, axon/dendrite length, neuron numbers, ATP6 expression and myotube length were quantified by immunocytochemistry.</p> </section> <section> <h3> Results</h3> <p>ws Rutin prevented cast immobilisation–induced memory deficits in young mice (<i>n</i> = 9; training vs. test, <i>p</i> = 0.0167) and increased Klotho in mRNA and protein levels in the brain. By orally administering Rutin, Rutin rapidly reached the blood, brain and skeletal muscles. Direct treatment of cultured hippocampal neurons with ws Rutin or conventional Rutin increased Klotho expression (<i>p</i> < 0.0001), axon length (<i>p</i> < 0.0001), dendrite number (<i>p</i> < 0.001) and neuron number (<i>p</i> < 0.0001). Recombinant Klotho treatment also increased hippocampal neuron numbers (<i>p</i> < 0.0001). In skeletal muscles, ws Rutin treatment enhanced mitochondrial protein MTCO1 expression in vivo (<i>n</i> = 5 mice, <i>p</i> = 0.0224). In myocytes,
{"title":"Oral Treatment of Water-Soluble Rutin Protects Against Cast Immobilisation–Induced Cognitive Impairment","authors":"Chihiro Tohda, Mizuho Kaneda, Tsukasa Nagase, Kaori Nomoto","doi":"10.1002/rco2.70016","DOIUrl":"https://doi.org/10.1002/rco2.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle atrophy is critical to cognitive decline, as evidenced in previous studies which showed that disuse-induced skeletal muscle atrophy in the hind limbs accelerated early cognitive decline in young Alzheimer's model 5XFAD mice and nontransgenic young mice. As physical activity is challenging for individuals with muscle loss due to aging or immobilisation, effective medications are needed to prevent cast immobilisation–induced cognitive decline. Rutin, a candidate medication for preventing muscle loss and cognitive decline, has numerous biological effects but is limited by its low bioavailability owing to water insolubility. EubioQuercetin (ws Rutin), a highly absorbable Rutin formula, offers over 2000-fold improved solubility. This study investigated whether oral water-soluble Rutin (ws Rutin) treatment prevents cast immobilisation–induced memory dysfunction in young mice and explored its underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Healthy young male ddY mice (10 weeks old) were used. Tissue distribution of Rutin was determined using LC-MS/MS at 0.5, 3, 6 and 16 h after oral administration of ws Rutin or conventional Rutin. Muscle atrophy was induced via bilateral hindlimb immobilisation by placing them in casts for 17 days. Cognitive function was evaluated using an object recognition test. RNA-seq was used to comprehensively analyse mRNA expression in the hippocampus and triceps surae. Expression levels of candidate molecules, affected by immobilisation and ws Rutin treatment, were confirmed using immunohistochemistry and Western blotting. Cultured hippocampal neurons and myocytes were treated with ws Rutin or Rutin, and parameters such as Klotho expression, axon/dendrite length, neuron numbers, ATP6 expression and myotube length were quantified by immunocytochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ws Rutin prevented cast immobilisation–induced memory deficits in young mice (<i>n</i> = 9; training vs. test, <i>p</i> = 0.0167) and increased Klotho in mRNA and protein levels in the brain. By orally administering Rutin, Rutin rapidly reached the blood, brain and skeletal muscles. Direct treatment of cultured hippocampal neurons with ws Rutin or conventional Rutin increased Klotho expression (<i>p</i> < 0.0001), axon length (<i>p</i> < 0.0001), dendrite number (<i>p</i> < 0.001) and neuron number (<i>p</i> < 0.0001). Recombinant Klotho treatment also increased hippocampal neuron numbers (<i>p</i> < 0.0001). In skeletal muscles, ws Rutin treatment enhanced mitochondrial protein MTCO1 expression in vivo (<i>n</i> = 5 mice, <i>p</i> = 0.0224). In myocytes, ","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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