Hun Jee Choe, Kyong Do Han, Ji-Hong Park, Jiwoo Lee, Mi Kyung Kwak, Yun Mi Choi, Sun-Joon Moon, Eun-Gyoung Hong
Background
Being underweight is an underrecognized risk factor for mortality among individuals with type 2 diabetes (T2D). This study aimed to evaluate the associations of underweight status with mortality among individuals with T2D.
Methods
This nationwide, retrospective, population-based cohort study used data from the Korean National Health Insurance Service. We included 1 788 996 adults with T2D who underwent baseline screening between 1 January 2015 and 31 December 2016, with follow-up through December 31, 2022. Underweight was defined as body mass index (BMI) < 18.5 kg/m2 and further categorized as mild (17.0–18.4 kg/m2), moderate (16.0–16.9 kg/m2), and severe (< 160 kg/m2). The primary outcome was all-cause mortality analysed using multivariable Cox proportional hazards regression.
Results
During a median follow-up of 6.96 years, 176 056 deaths occurred. Compared with the non-underweight group (BMI ≥ 18.5 kg/m2), all-cause mortality increased stepwise across underweight categories, with adjusted hazard ratios (aHRs) of 2.037 (95% CI, 1.982–2.094) for mild underweight, 2.719 (2.587–2.857) for moderate underweight, and 3.876 (3.646–4.119) for severe underweight. Cause-specific mortality showed similar gradients. For diabetes-related mortality, the aHRs were 2.265 (2.073–2.474), 3.306 (2.845–3.843) and 5.136 (4.300–6.134) across mild, moderate and severe underweight, respectively; for cardiovascular mortality, 1.881 (1.721–2.055), 2.087 (1.751–2.487) and 2.825 (2.267–3.519); and for cerebrovascular mortality, 2.100 (1.881–2.344), 2.300 (1.846–2.866) and 3.501 (2.702–4.537). Notably, the severe underweight group (BMI < 16.0 kg/m2) showed significantly higher all-cause mortality than the severe obesity group (BMI ≥ 35.0 kg/m2) when compared to the BMI 25.0–29.9 kg/m2 reference group (aHR [95% CI]: 5.168 [4.857–5.499] vs. 1.504 [1.418–1.595]).
Conclusions
Among individuals with T2D, underweight status was associated with substantially elevated mortality risks, with severe underweight exhibiting greater risk than severe obesity.
{"title":"Underweight and Mortality in Type 2 Diabetes: A Nationwide Retrospective Cohort Study","authors":"Hun Jee Choe, Kyong Do Han, Ji-Hong Park, Jiwoo Lee, Mi Kyung Kwak, Yun Mi Choi, Sun-Joon Moon, Eun-Gyoung Hong","doi":"10.1002/jcsm.70145","DOIUrl":"10.1002/jcsm.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Being underweight is an underrecognized risk factor for mortality among individuals with type 2 diabetes (T2D). This study aimed to evaluate the associations of underweight status with mortality among individuals with T2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This nationwide, retrospective, population-based cohort study used data from the Korean National Health Insurance Service. We included 1 788 996 adults with T2D who underwent baseline screening between 1 January 2015 and 31 December 2016, with follow-up through December 31, 2022. Underweight was defined as body mass index (BMI) < 18.5 kg/m<sup>2</sup> and further categorized as mild (17.0–18.4 kg/m<sup>2</sup>), moderate (16.0–16.9 kg/m<sup>2</sup>), and severe (< 160 kg/m<sup>2</sup>). The primary outcome was all-cause mortality analysed using multivariable Cox proportional hazards regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a median follow-up of 6.96 years, 176 056 deaths occurred. Compared with the non-underweight group (BMI ≥ 18.5 kg/m<sup>2</sup>), all-cause mortality increased stepwise across underweight categories, with adjusted hazard ratios (aHRs) of 2.037 (95% CI, 1.982–2.094) for mild underweight, 2.719 (2.587–2.857) for moderate underweight, and 3.876 (3.646–4.119) for severe underweight. Cause-specific mortality showed similar gradients. For diabetes-related mortality, the aHRs were 2.265 (2.073–2.474), 3.306 (2.845–3.843) and 5.136 (4.300–6.134) across mild, moderate and severe underweight, respectively; for cardiovascular mortality, 1.881 (1.721–2.055), 2.087 (1.751–2.487) and 2.825 (2.267–3.519); and for cerebrovascular mortality, 2.100 (1.881–2.344), 2.300 (1.846–2.866) and 3.501 (2.702–4.537). Notably, the severe underweight group (BMI < 16.0 kg/m<sup>2</sup>) showed significantly higher all-cause mortality than the severe obesity group (BMI ≥ 35.0 kg/m<sup>2</sup>) when compared to the BMI 25.0–29.9 kg/m<sup>2</sup> reference group (aHR [95% CI]: 5.168 [4.857–5.499] vs. 1.504 [1.418–1.595]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among individuals with T2D, underweight status was associated with substantially elevated mortality risks, with severe underweight exhibiting greater risk than severe obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680149","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}
Xiaoqin Luo, Mengxue Zhang, Lili Chen, Ruichang Wang, Jiabing Lian, Zhe Yang, Renato V. lozzo, Jin Wang, Yan Zhang, Xiuli Bi
<div> <section> <h3> Background</h3> <p>Primary sarcopenia is an age-associated disorder with progressive and generalised loss of skeletal muscle strength and mass. Skeletal muscle fibrosis is one of the significant pathological manifestations of age-associated sarcopenia. Decorin, a small dermatan–sulfate proteoglycan, participates in extracellular matrix assembly. In numerous studies, the involvement of decorin is not restricted to matrix structural proteins, and it also affects a diverse variety of biological functions like cell growth, adhesion, migration, proliferation and differentiation. Additionally, it modulates the process of inflammation and fibrillogenesis. Based on these preclinical evidences, we hypothesised that decorin may potentially play an important role in skeletal muscles during ageing.</p> </section> <section> <h3> Methods</h3> <p>Natural ageing mice (Dcn<sup>+/+</sup>), D-galactose (D-gal)–induced Dcn<sup>+/+</sup>, Dcn<sup>−/−</sup> mice and NOR-10 cell models were established. Grip strength and exercise capacity were evaluated, after the mice were sacrificed to collect their gastrocnemius muscles for assessment of atrophy and fibrosis by haematoxylin and eosin staining, qRT-PCR and Western blotting. Co-immunoprecipitation was used to identify the interaction between decorin and integrin β1 (ITGB1).</p> </section> <section> <h3> Results</h3> <p>The expression levels of decorin were reduced at both mRNA and protein levels in muscle during natural ageing in mice (−75.3% of mRNA level; −29.5% of protein level) and NOR-10 cells (−78% of protein level). <i>si-Dcn</i> promoted the expression of α-SMA (+37.2%) and fibronectin (+53.1%), which are related to muscle fibrosis in D-gal–induced NOR-10 cells. In addition, in Dcn<sup>−/−</sup>–D-gal mice, which exhibited more aggravated muscle atrophy including smaller grip strength (−21.7%, <i>p</i> < 0.001), downregulation of the ratio of gastrocnemius weight (−7.3%), fibre size (Gast: −15.3%) and increased levels of α-SMA (+70.2%), MuRF-1 (+30.2%), NLRP3(+19.4%) and p21(+27.2%) proteins compared with Dcn<sup>+/+</sup>–D-gal mice. In terms of the underlying mechanisms, the Akt/mTOR signalling pathway was downregulated in Dcn<sup>−/−</sup>–D-gal mice compared with aged Dcn<sup>+/+</sup>–D-gal mice (p-S473-Akt/Akt: −38.1%; p-Ser2448-mTOR/mTOR: −28.8%; p-p70S6K/p70: −40.3%; p-4E-BP1: −42.3%, <i>p</i> < 0.05). Decorin activation enhanced ITGB1 expression (+46.7% vs. NC, <i>p</i> < 0.01). si-ITGB1 suppressed the expression of p-S473-Akt and p-Ser2448-mTOR in NOR-10 cells with Dcn overexpression. The interaction between decorin and ITGB1 was found in skeletal muscle, suggesting that t
{"title":"Decorin Deficiency Promotes D-Galactose–Induced Skeletal Muscle Atrophy and Fibrosis by Regulating ITGB1/Akt/mTOR Signalling Pathway","authors":"Xiaoqin Luo, Mengxue Zhang, Lili Chen, Ruichang Wang, Jiabing Lian, Zhe Yang, Renato V. lozzo, Jin Wang, Yan Zhang, Xiuli Bi","doi":"10.1002/jcsm.70144","DOIUrl":"10.1002/jcsm.70144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Primary sarcopenia is an age-associated disorder with progressive and generalised loss of skeletal muscle strength and mass. Skeletal muscle fibrosis is one of the significant pathological manifestations of age-associated sarcopenia. Decorin, a small dermatan–sulfate proteoglycan, participates in extracellular matrix assembly. In numerous studies, the involvement of decorin is not restricted to matrix structural proteins, and it also affects a diverse variety of biological functions like cell growth, adhesion, migration, proliferation and differentiation. Additionally, it modulates the process of inflammation and fibrillogenesis. Based on these preclinical evidences, we hypothesised that decorin may potentially play an important role in skeletal muscles during ageing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Natural ageing mice (Dcn<sup>+/+</sup>), D-galactose (D-gal)–induced Dcn<sup>+/+</sup>, Dcn<sup>−/−</sup> mice and NOR-10 cell models were established. Grip strength and exercise capacity were evaluated, after the mice were sacrificed to collect their gastrocnemius muscles for assessment of atrophy and fibrosis by haematoxylin and eosin staining, qRT-PCR and Western blotting. Co-immunoprecipitation was used to identify the interaction between decorin and integrin β1 (ITGB1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression levels of decorin were reduced at both mRNA and protein levels in muscle during natural ageing in mice (−75.3% of mRNA level; −29.5% of protein level) and NOR-10 cells (−78% of protein level). <i>si-Dcn</i> promoted the expression of α-SMA (+37.2%) and fibronectin (+53.1%), which are related to muscle fibrosis in D-gal–induced NOR-10 cells. In addition, in Dcn<sup>−/−</sup>–D-gal mice, which exhibited more aggravated muscle atrophy including smaller grip strength (−21.7%, <i>p</i> < 0.001), downregulation of the ratio of gastrocnemius weight (−7.3%), fibre size (Gast: −15.3%) and increased levels of α-SMA (+70.2%), MuRF-1 (+30.2%), NLRP3(+19.4%) and p21(+27.2%) proteins compared with Dcn<sup>+/+</sup>–D-gal mice. In terms of the underlying mechanisms, the Akt/mTOR signalling pathway was downregulated in Dcn<sup>−/−</sup>–D-gal mice compared with aged Dcn<sup>+/+</sup>–D-gal mice (p-S473-Akt/Akt: −38.1%; p-Ser2448-mTOR/mTOR: −28.8%; p-p70S6K/p70: −40.3%; p-4E-BP1: −42.3%, <i>p</i> < 0.05). Decorin activation enhanced ITGB1 expression (+46.7% vs. NC, <i>p</i> < 0.01). si-ITGB1 suppressed the expression of p-S473-Akt and p-Ser2448-mTOR in NOR-10 cells with Dcn overexpression. The interaction between decorin and ITGB1 was found in skeletal muscle, suggesting that t","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680151","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}
Aiwen Jiang, Yi Liu, Luyao Wang, Haifei Wang, Shenglong Wu, Wenbin Bao
<div> <section> <h3> Background</h3> <p>Apoptosis coincides with the differentiation of skeletal myoblasts, and numerous studies have shown that the apoptotic activity is required for myogenic differentiation. Although the role of apoptosis in skeletal muscle differentiation has been well documented, its mechanism is largely unknown.</p> </section> <section> <h3> Methods</h3> <p>Apoptotic extracellular vesicles (apoVs) were extracted from differentiated C2C12 cells or STS-treated undifferentiated C2C12 myoblasts. C2C12 myoblasts, 8-week-old male mice or 15-month-old male mice were used as in vitro and in vivo models, respectively. These models were treated with C2C12-derived apoVs to explore the biological function and mechanism of apoVs in myogenic differentiation, skeletal muscle development and aging.</p> </section> <section> <h3> Results</h3> <p>Proteomic analysis revealed that inhibition of apoptotic activity by Z-VAD-FMK (ZVAD) affected extracellular components. Using immunofluorescence staining, western blotting and transmission electron microscopy analysis, our results demonstrated the generation of apoVs during myogenic differentiation. C2C12-derived apoVs exhibited a typical double-membrane spherical structure, phosphatidylserine exposure and were highly positive for the general apoV markers cleaved caspase 3 (CASP3), Alix and TSG101. Inhibition of apoptotic activity significantly reduced (<i>p</i> = 0.0029) the protein level of myosin heavy chain (1.05 in the Con group vs. 0.38 in the ZVAD group) accompanied by a marked decrease (<i>p</i> < 0.0001) in apoV production (5.91e+10 ± 8.93e+09 in the Con group vs. 1.77e+10 ± 1.36e+09 in the ZVAD group). Proteomic analysis of apoVs suggested that C2C12-derived apoVs contain multiple pro-differentiation proteins, including insulin-like growth factor 1 receptor (Igf1r). ApoVs could be taken up by recipient cells and subsequently rescued the impaired C2C12 differentiation induced by ZVAD (<i>p</i> < 0.0001) and promoted the normal myogenic differentiation process (<i>p</i> = 0.0081) by carrying Igf1r and promoting PI3K/AKT/mTOR activation. Knockdown of Igf1r or inhibition of PI3K activation diminished the positive role of apoVs. In addition, apoV treatment promoted skeletal muscle development in 8-week-old male mice (<i>n</i> = 6, Cohen's d = 1.993, power = 0.874) and relieved age-related muscle loss (<i>n</i> = 6, Cohen's d = 3.97, power = 0.999).</p> </section> <section> <h3> Conclusions</h3> <p>In summary, this study demonstrates the generation of apoVs during myogenic differentiation. Th
{"title":"C2C12-Derived ApoVs Promote Skeletal Muscle Development and Ameliorate Age-Related Muscle Loss Through Igf1r/PI3K/AKT/mTOR Pathway","authors":"Aiwen Jiang, Yi Liu, Luyao Wang, Haifei Wang, Shenglong Wu, Wenbin Bao","doi":"10.1002/jcsm.70159","DOIUrl":"10.1002/jcsm.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Apoptosis coincides with the differentiation of skeletal myoblasts, and numerous studies have shown that the apoptotic activity is required for myogenic differentiation. Although the role of apoptosis in skeletal muscle differentiation has been well documented, its mechanism is largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Apoptotic extracellular vesicles (apoVs) were extracted from differentiated C2C12 cells or STS-treated undifferentiated C2C12 myoblasts. C2C12 myoblasts, 8-week-old male mice or 15-month-old male mice were used as in vitro and in vivo models, respectively. These models were treated with C2C12-derived apoVs to explore the biological function and mechanism of apoVs in myogenic differentiation, skeletal muscle development and aging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Proteomic analysis revealed that inhibition of apoptotic activity by Z-VAD-FMK (ZVAD) affected extracellular components. Using immunofluorescence staining, western blotting and transmission electron microscopy analysis, our results demonstrated the generation of apoVs during myogenic differentiation. C2C12-derived apoVs exhibited a typical double-membrane spherical structure, phosphatidylserine exposure and were highly positive for the general apoV markers cleaved caspase 3 (CASP3), Alix and TSG101. Inhibition of apoptotic activity significantly reduced (<i>p</i> = 0.0029) the protein level of myosin heavy chain (1.05 in the Con group vs. 0.38 in the ZVAD group) accompanied by a marked decrease (<i>p</i> < 0.0001) in apoV production (5.91e+10 ± 8.93e+09 in the Con group vs. 1.77e+10 ± 1.36e+09 in the ZVAD group). Proteomic analysis of apoVs suggested that C2C12-derived apoVs contain multiple pro-differentiation proteins, including insulin-like growth factor 1 receptor (Igf1r). ApoVs could be taken up by recipient cells and subsequently rescued the impaired C2C12 differentiation induced by ZVAD (<i>p</i> < 0.0001) and promoted the normal myogenic differentiation process (<i>p</i> = 0.0081) by carrying Igf1r and promoting PI3K/AKT/mTOR activation. Knockdown of Igf1r or inhibition of PI3K activation diminished the positive role of apoVs. In addition, apoV treatment promoted skeletal muscle development in 8-week-old male mice (<i>n</i> = 6, Cohen's d = 1.993, power = 0.874) and relieved age-related muscle loss (<i>n</i> = 6, Cohen's d = 3.97, power = 0.999).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, this study demonstrates the generation of apoVs during myogenic differentiation. Th","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673551","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}
Andreas Nilsson, Hadil Limem, Aurelia Santoro, Laura Smeldy Jurado-Medina, Agnes A. M. Berendsen, Lisette C. P. G. M. de Groot, Joanna Kaluza, Ewa Sicińska, Amy Jennings, Susan Fairweather-Tait, Alberto Bazzocchi, Giuseppe Battista, Claudio Franceschi, Tarak Driss, Fawzi Kadi
<div> <section> <h3> Background</h3> <p>Sarcopenic obesity (SO) is characterized by the presence of both obesity and sarcopenia and is related to disability and loss of independence in older adults. The extent to which time spent in light physical activity (LPA), or moderate-to-vigorous physical activity (MVPA) is associated with SO risk in older adults remains unclear. The aim of this study was (a) to examine the association between the level of adherence to recommended amounts of MVPA and the risk of SO in older adults and (b) to determine whether time spent in LPA is associated with SO risk independently of time spent in MVPA.</p> </section> <section> <h3> Methods</h3> <p>This cross-sectional study involved 862 community-dwelling older adults (58% women; aged 65–79 years) from four European countries. Accelerometer-determined time in MVPA was categorized as follows: inactive (< 75 min/week), moderately active (75–149 min/week), active (150–299 min/week) and highly active (≥ 300 min/week). Time in LPA was expressed in tertiles. The outcome measure SO risk was determined based on appendicular lean mass, waist circumference, handgrip strength and the 5-times sit-to-stand test. Odds ratios (OR) with a 95% confidence interval (95% CI) of high SO risk across levels of MVPA and LPA were determined by binary logistic regression adjusted for the level of systemic inflammation (high-sensitivity C-reactive protein) and dietary protein intake.</p> </section> <section> <h3> Results</h3> <p>Compared to the inactive group, ORs of having a high SO risk were about 50%–80% lower, depending on the MVPA level, with the largest risk reduction in the highly active group (OR: 0.23, 95% CI: 0.13–0.39; <i>p</i> < 0.05). The likelihood of having a high SO risk was significantly lower among the highly active group compared to the active group (OR: 0.50; 95% CI: 0.33–0.77; <i>p</i> < 0.05). More time in LPA was associated with a significantly lower likelihood of having high SO risk (highest vs. lowest tertile: OR: 0.52, 95% CI: 0.30–0.89; <i>p</i> < 0.05) only in participants with low amounts of MVPA. In contrast, LPA was not associated with SO risk among participants meeting the MVPA recommendation.</p> </section> <section> <h3> Conclusions</h3> <p>MVPA is strongly associated with a lower likelihood of having a high SO risk in older adults, independently of the level of systemic inflammation and intakes of dietary proteins. LPA is related to SO risk in sedentary older adults, which supports the promotion of physical activity regardless of intensity for mitigat
背景：肌少性肥胖（SO）以肥胖和肌少症同时存在为特征，与老年人的残疾和独立性丧失有关。在老年人中，轻度体力活动（LPA）或中度至剧烈体力活动（MVPA）所花费的时间与SO风险的关联程度尚不清楚。本研究的目的是(a)检查老年人坚持MVPA推荐量的水平与SO风险之间的关系，以及(b)确定LPA的时间是否独立于MVPA的时间与SO风险相关。方法：这项横断面研究涉及来自四个欧洲国家的862名社区居住的老年人（58%为女性，65-79岁）。加速度计测定的MVPA时间分为：不活跃（75分钟/周）、中度活跃（75 - 149分钟/周）、活跃（150-299分钟/周）和高度活跃（≥300分钟/周）。LPA时间以单位表示。结果测量SO风险是根据阑尾瘦质量、腰围、握力和5次坐立测试来确定的。通过二元logistic回归确定MVPA和LPA水平的高SO风险的95%置信区间（95% CI）的优势比（OR），调整了全身炎症水平（高敏感性C反应蛋白）和饮食蛋白质摄入量。结果与不活动组相比，根据MVPA水平不同，高SO风险的OR降低约50%-80%，其中高度活动组风险降低最大（OR: 0.23, 95% CI: 0.13-0.39; p < 0.05）。与运动组相比，高度运动组患SO高风险的可能性显著降低（OR: 0.50; 95% CI: 0.33-0.77; p < 0.05）。只有在MVPA水平较低的参与者中，LPA时间较长与发生高SO风险的可能性显著降低相关（最高与最低比值：OR: 0.52, 95% CI: 0.30-0.89; p < 0.05）。相比之下，在符合MVPA建议的参与者中，LPA与SO风险无关。结论：MVPA与老年人发生高SO风险的可能性较低密切相关，与全身性炎症水平和膳食蛋白质摄入量无关。在久坐的老年人中，LPA与SO风险有关，这支持了促进身体活动，无论强度如何，都可以减轻SO。
{"title":"Accelerometer-Determined Physical Activity and Sarcopenic Obesity Risk in Older European Men and Women","authors":"Andreas Nilsson, Hadil Limem, Aurelia Santoro, Laura Smeldy Jurado-Medina, Agnes A. M. Berendsen, Lisette C. P. G. M. de Groot, Joanna Kaluza, Ewa Sicińska, Amy Jennings, Susan Fairweather-Tait, Alberto Bazzocchi, Giuseppe Battista, Claudio Franceschi, Tarak Driss, Fawzi Kadi","doi":"10.1002/jcsm.70149","DOIUrl":"10.1002/jcsm.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenic obesity (SO) is characterized by the presence of both obesity and sarcopenia and is related to disability and loss of independence in older adults. The extent to which time spent in light physical activity (LPA), or moderate-to-vigorous physical activity (MVPA) is associated with SO risk in older adults remains unclear. The aim of this study was (a) to examine the association between the level of adherence to recommended amounts of MVPA and the risk of SO in older adults and (b) to determine whether time spent in LPA is associated with SO risk independently of time spent in MVPA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study involved 862 community-dwelling older adults (58% women; aged 65–79 years) from four European countries. Accelerometer-determined time in MVPA was categorized as follows: inactive (< 75 min/week), moderately active (75–149 min/week), active (150–299 min/week) and highly active (≥ 300 min/week). Time in LPA was expressed in tertiles. The outcome measure SO risk was determined based on appendicular lean mass, waist circumference, handgrip strength and the 5-times sit-to-stand test. Odds ratios (OR) with a 95% confidence interval (95% CI) of high SO risk across levels of MVPA and LPA were determined by binary logistic regression adjusted for the level of systemic inflammation (high-sensitivity C-reactive protein) and dietary protein intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the inactive group, ORs of having a high SO risk were about 50%–80% lower, depending on the MVPA level, with the largest risk reduction in the highly active group (OR: 0.23, 95% CI: 0.13–0.39; <i>p</i> < 0.05). The likelihood of having a high SO risk was significantly lower among the highly active group compared to the active group (OR: 0.50; 95% CI: 0.33–0.77; <i>p</i> < 0.05). More time in LPA was associated with a significantly lower likelihood of having high SO risk (highest vs. lowest tertile: OR: 0.52, 95% CI: 0.30–0.89; <i>p</i> < 0.05) only in participants with low amounts of MVPA. In contrast, LPA was not associated with SO risk among participants meeting the MVPA recommendation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MVPA is strongly associated with a lower likelihood of having a high SO risk in older adults, independently of the level of systemic inflammation and intakes of dietary proteins. LPA is related to SO risk in sedentary older adults, which supports the promotion of physical activity regardless of intensity for mitigat","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673614","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}
Eric J. Roeland, Florian J. Fintelmann, Ruoyong Yang, Lisa Tarasenko, Philip D. Bonomi
<div> <section> <h3> Background</h3> <p>Weight stabilization or gain during cancer treatment is associated with increased survival. Analyses of weight gain by sex during cancer treatment and the effects of weight on survival have not been fully studied. This post hoc analysis retrospectively examined the relationship between sex, weight gain and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) receiving standard-of-care chemotherapy.</p> </section> <section> <h3> Methods</h3> <p>Data from the control arms of three randomized phase III clinical studies (NCT00596830, NCT00254891, NCT00254904) of adult patients with advanced NSCLC were pooled; patients received platinum-based doublet chemotherapy. Weight was recorded according to each study's schedule. Analyses compared weight gain categories from baseline up to 3 months after chemotherapy initiation (> 0% vs. ≤ 0%, > 2.5% vs. ≤ 2.5% and > 5% vs. ≤ 5%). Stepwise Cox proportional hazards modelling of OS (time from treatment initiation to death due to any cause) was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs); differences between groups were tested with log-rank tests.</p> </section> <section> <h3> Results</h3> <p>Of the 1030 patients, most were men (70.5%) with stage IV NSCLC. Median (range) age was 62 (34–87) years for men and 60 (34–83) years for women, and the mean body mass index (standard deviation) was 24.5 (4.2) and 24.8 kg/m<sup>2</sup> (4.8), respectively. Weight gain of > 0%, > 2.5% and > 5% was observed in 44.0%, 24.5% and 11.7% of the patients, respectively. Any weight gain (> 0% vs. ≤ 0%) was associated with a significantly reduced risk of death in both men (HR 0.62 [95% CI 0.522, 0.742]; <i>p</i> < 0.0001) and women (HR 0.68 [95% CI 0.512, 0.910]; <i>p</i> = 0.0092). Weight gain of > 2.5% vs. ≤ 2.5% was associated with a significantly reduced risk of death in men (HR 0.64; 95% CI 0.516, 0.784; <i>p</i> < 0.0001) and a risk reduction in women (HR 0.73; 95% CI 0.518, 1.034; <i>p</i> = 0.0767). Weight gain of > 5% vs. ≤ 5% was associated with a significantly reduced risk of death in men (HR 0.67; 95% CI 0.503, 0.879; <i>p</i> = 0.0042), but not in women (HR 0.90; 95% CI 0.542, 1.509; <i>p</i> = 0.70). Despite these differences, the overall interaction of weight gain by sex was not significant (<i>p</i> = 0.61 for > 0% vs. ≤ 0%, <i>p</i> = 0.43 for > 2.5% vs. ≤ 2.5% and <i>p</i> = 0.37 for > 5% vs. ≤ 5%).</p> </section> <section> <h3> Conclusions</h3> <p>Any weight gain during treatment of
背景：癌症治疗期间体重稳定或增加与生存率增加有关。在癌症治疗期间，性别对体重增加的分析以及体重对生存的影响还没有得到充分的研究。这项事后分析回顾性研究了接受标准治疗化疗的晚期非小细胞肺癌（NSCLC）患者的性别、体重增加和总生存期（OS）之间的关系。方法收集来自3个随机III期临床研究（NCT00596830、NCT00254891、NCT00254904）的成年晚期NSCLC患者对照组数据；患者接受以铂为基础的双重化疗。根据每个研究的时间表记录体重。分析比较了从基线到化疗开始后3个月的体重增加类别（> 0% vs.≤0%,> 2.5% vs.≤2.5%,> 5% vs.≤5%）。使用OS（从治疗开始到任何原因导致的死亡时间）的逐步Cox比例风险模型以95%置信区间（ci）估计风险比（hr）；组间差异采用log-rank检验。结果1030例患者中，大多数为IV期NSCLC男性（70.5%）。男性年龄中位数（范围）为62（34-87）岁，女性年龄中位数（范围）为60（34-83）岁，平均体重指数（标准差）分别为24.5（4.2）和24.8 kg/m2（4.8）。分别有44.0%、24.5%和11.7%的患者体重增加> 0%、> 2.5%和> 5%。任何体重增加(> 0%比≤0%)与男性死亡的风险显著降低(HR 0.62 (95% CI 0.522, 0.742); p 2.5%比≤2.5%的死亡风险显著降低男性(HR 0.64; 95%可信区间0.516,0.784;p 5%比≤5%的死亡风险显著降低男性(HR 0.67; 95%可信区间0.503,0.879;p = 0.0042),但不是在女性(HR 0.90; 95%可信区间0.542,1.509;p = 0.70)。尽管存在这些差异，但性别体重增加的总体相互作用并不显著（> % vs.≤0% p = 0.61, > 2.5% vs.≤2.5% p = 0.43, > 5% vs.≤5% p = 0.37）。结论：晚期非小细胞肺癌治疗期间体重增加与死亡风险显著降低相关，与性别无关。审判REGISTRATIONNCT00596830;NCT00254891;NCT00254904。
{"title":"Evaluation of Weight Gain and Overall Survival of Men Versus Women With Advanced Non-Small Cell Lung Cancer","authors":"Eric J. Roeland, Florian J. Fintelmann, Ruoyong Yang, Lisa Tarasenko, Philip D. Bonomi","doi":"10.1002/jcsm.70131","DOIUrl":"10.1002/jcsm.70131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Weight stabilization or gain during cancer treatment is associated with increased survival. Analyses of weight gain by sex during cancer treatment and the effects of weight on survival have not been fully studied. This post hoc analysis retrospectively examined the relationship between sex, weight gain and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) receiving standard-of-care chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from the control arms of three randomized phase III clinical studies (NCT00596830, NCT00254891, NCT00254904) of adult patients with advanced NSCLC were pooled; patients received platinum-based doublet chemotherapy. Weight was recorded according to each study's schedule. Analyses compared weight gain categories from baseline up to 3 months after chemotherapy initiation (> 0% vs. ≤ 0%, > 2.5% vs. ≤ 2.5% and > 5% vs. ≤ 5%). Stepwise Cox proportional hazards modelling of OS (time from treatment initiation to death due to any cause) was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs); differences between groups were tested with log-rank tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 1030 patients, most were men (70.5%) with stage IV NSCLC. Median (range) age was 62 (34–87) years for men and 60 (34–83) years for women, and the mean body mass index (standard deviation) was 24.5 (4.2) and 24.8 kg/m<sup>2</sup> (4.8), respectively. Weight gain of > 0%, > 2.5% and > 5% was observed in 44.0%, 24.5% and 11.7% of the patients, respectively. Any weight gain (> 0% vs. ≤ 0%) was associated with a significantly reduced risk of death in both men (HR 0.62 [95% CI 0.522, 0.742]; <i>p</i> < 0.0001) and women (HR 0.68 [95% CI 0.512, 0.910]; <i>p</i> = 0.0092). Weight gain of > 2.5% vs. ≤ 2.5% was associated with a significantly reduced risk of death in men (HR 0.64; 95% CI 0.516, 0.784; <i>p</i> < 0.0001) and a risk reduction in women (HR 0.73; 95% CI 0.518, 1.034; <i>p</i> = 0.0767). Weight gain of > 5% vs. ≤ 5% was associated with a significantly reduced risk of death in men (HR 0.67; 95% CI 0.503, 0.879; <i>p</i> = 0.0042), but not in women (HR 0.90; 95% CI 0.542, 1.509; <i>p</i> = 0.70). Despite these differences, the overall interaction of weight gain by sex was not significant (<i>p</i> = 0.61 for > 0% vs. ≤ 0%, <i>p</i> = 0.43 for > 2.5% vs. ≤ 2.5% and <i>p</i> = 0.37 for > 5% vs. ≤ 5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Any weight gain during treatment of","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657068","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}
Jiawei Zhou, Benyam Muluneh, Quefeng Li, Lynne I. Wagner, Yuchen Wang, Jim H. Hughes
<div> <section> <h3> Background</h3> <p>Appetite loss is a common and distressing symptom in non-small-cell lung cancer (NSCLC), driven by both treatment side effects and disease progression. It often leads to unintended weight loss and cancer cachexia, significantly impairing patients' quality of life and survival. Yet, appetite loss remains under-recognized in oncology care, with no standard assessment tools or universal management guidelines. In this study, we developed a predictive model to identify clinically meaningful thresholds of appetite loss that were associated with significant weight reduction and decreased survival. We aim to highlight the clinical consequences of appetite loss and advocate for more patient-centred treatment strategies that address this often overlooked but impactful symptom in cancer care.</p> </section> <section> <h3> Methods</h3> <p>We analysed longitudinal patient-reported appetite scores, measured by the Lung Cancer Symptom Scale (LCSS), and body weight data from 476 NSCLC patients receiving supportive care and recovering from prior chemoradiotherapy (recovering cohort). A mechanism-based population modelling approach was used to predict the impact of appetite changes on body weight, accounting for significant data variability. Model validation was conducted using data from 380 NSCLC patients undergoing docetaxel chemotherapy (chemotherapy cohort). Clinically meaningful appetite loss thresholds were determined based on the model-predicted appetite loss associated with a 3.5-kg body weight loss and significantly worse survival (hazard ratio > 1, <i>p</i> < 0.05).</p> </section> <section> <h3> Results</h3> <p>We found that, according to the LCSS (100-mm visual analogue scale), a 30-mm (90% CI, 28–32) improvement in appetite corresponded to a 3.5-kg weight gain in the recovering cohort, while a 23-mm (90% CI, 17–30) decline correlated with a 3.5-kg weight loss in the chemotherapy cohort. Significant associations were observed between appetite loss trajectories and overall survival (<i>p</i> < 0.001). Clinically meaningful thresholds for appetite loss were identified as 4 mm at 1 month and 11 mm at 3 months, both significantly associated with reduced OS in patients receiving docetaxel chemotherapy (<i>p</i> < 0.05).</p> </section> <section> <h3> Conclusions</h3> <p>We developed a population predictive model to characterize the relationship between patient-reported appetite and body weight, identifying clinically meaningful thresholds for appetite loss. This work highlights the importance of managing appet
{"title":"From Symptom to Outcome: Defining Clinically Meaningful Patient-Reported Appetite Loss in Non-Small-Cell Lung Cancer","authors":"Jiawei Zhou, Benyam Muluneh, Quefeng Li, Lynne I. Wagner, Yuchen Wang, Jim H. Hughes","doi":"10.1002/jcsm.70150","DOIUrl":"10.1002/jcsm.70150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Appetite loss is a common and distressing symptom in non-small-cell lung cancer (NSCLC), driven by both treatment side effects and disease progression. It often leads to unintended weight loss and cancer cachexia, significantly impairing patients' quality of life and survival. Yet, appetite loss remains under-recognized in oncology care, with no standard assessment tools or universal management guidelines. In this study, we developed a predictive model to identify clinically meaningful thresholds of appetite loss that were associated with significant weight reduction and decreased survival. We aim to highlight the clinical consequences of appetite loss and advocate for more patient-centred treatment strategies that address this often overlooked but impactful symptom in cancer care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed longitudinal patient-reported appetite scores, measured by the Lung Cancer Symptom Scale (LCSS), and body weight data from 476 NSCLC patients receiving supportive care and recovering from prior chemoradiotherapy (recovering cohort). A mechanism-based population modelling approach was used to predict the impact of appetite changes on body weight, accounting for significant data variability. Model validation was conducted using data from 380 NSCLC patients undergoing docetaxel chemotherapy (chemotherapy cohort). Clinically meaningful appetite loss thresholds were determined based on the model-predicted appetite loss associated with a 3.5-kg body weight loss and significantly worse survival (hazard ratio > 1, <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that, according to the LCSS (100-mm visual analogue scale), a 30-mm (90% CI, 28–32) improvement in appetite corresponded to a 3.5-kg weight gain in the recovering cohort, while a 23-mm (90% CI, 17–30) decline correlated with a 3.5-kg weight loss in the chemotherapy cohort. Significant associations were observed between appetite loss trajectories and overall survival (<i>p</i> < 0.001). Clinically meaningful thresholds for appetite loss were identified as 4 mm at 1 month and 11 mm at 3 months, both significantly associated with reduced OS in patients receiving docetaxel chemotherapy (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We developed a population predictive model to characterize the relationship between patient-reported appetite and body weight, identifying clinically meaningful thresholds for appetite loss. This work highlights the importance of managing appet","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664505","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}
Dan Xie, Yuru Xiao, Xuexin Li, Bowen Sun, Jianguo Feng, Jing Jia, Jie Li, Yun Wang, Fei He, Li Liu
Background
Ventilator-induced diaphragmatic dysfunction (VIDD) is a major complication in critically ill patients. Prolonged mechanical ventilation (MV) triggers diaphragmatic fibrotic remodelling, but the underlying mechanisms remain unclear. This study investigated the role of the mechanosensitive channel Piezo1 in this process.
Methods
A rat model of MV was established for 6 or 12 h. Diaphragm structure (atrophy and fibrosis) and function (frequency-contraction curve and fatigue index) were assessed. The roles of Piezo1 were probed using the inhibitor GsMTx4 (a nonspecific mechanosensitive channel inhibitor) and adeno-associated virus (AAV)–mediated knockdown. Downstream signalling was identified by RNA sequencing (RNA-seq) and validated with cytosporone-B (CsnB, a specific agonist of Nr4a1).
Results
Compared with controls, MV for 12 h induced significant diaphragm fibrosis, atrophy and dysfunction, alongside increased Piezo1 expression (mRNA: 2.362 ± 0.429 vs. 0.920 ± 0.363, p = 0.0018; protein: 1.098 ± 0.103 vs. 0.676 ± 0.102, p = 0.0007). Both GsMTx4 and Piezo1 knockdown alleviated these effects. Knockdown reduced the collagen deposition area by approximately 21% and downregulated key fibrotic markers including fibronectin (0.749 ± 0.118 vs. 1.081 ± 0.117, p < 0.0001), collagen 1 (0.703 ± 0.087 vs. 1.155 ± 0.131, p < 0.0001), collagen 3 (0.879 ± 0.074 vs. 1.063 ± 0.068, p = 0.022) and α-SMA (0.872 ± 0.657 vs. 1.108 ± 0.078, p = 0.0031) compared to the MV12 + shCtrl group. RNA-seq identified Nr4a1 as a downstream factor (p value < 0.009). CsnB treatment increased Nr4a1 expression (1.128 ± 0.113 vs. 0.490 ± 0.084, p < 0.0001), mitigating prolonged MV-induced diaphragm fibrosis and dysfunction but not atrophy (938.1 ± 116.2 vs. 754.7 ± 155.5, p = 0.1079).
Conclusions
Piezo1 upregulation is a key mechanism in ventilator-induced diaphragm fibrosis, potentially mediated through the Akt/Nr4a1 signalling pathway. Targeted inhibition of Piezo1 or activation of Nr4a1 presents a promising therapeutic strategy to prevent fibrosis and preserve diaphragm function.
{"title":"Mechanosensitive Piezo1 Channels Mediate Diaphragm Fibrosis Induced by Prolonged Mechanical Ventilation","authors":"Dan Xie, Yuru Xiao, Xuexin Li, Bowen Sun, Jianguo Feng, Jing Jia, Jie Li, Yun Wang, Fei He, Li Liu","doi":"10.1002/jcsm.70136","DOIUrl":"10.1002/jcsm.70136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ventilator-induced diaphragmatic dysfunction (VIDD) is a major complication in critically ill patients. Prolonged mechanical ventilation (MV) triggers diaphragmatic fibrotic remodelling, but the underlying mechanisms remain unclear. This study investigated the role of the mechanosensitive channel Piezo1 in this process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A rat model of MV was established for 6 or 12 h. Diaphragm structure (atrophy and fibrosis) and function (frequency-contraction curve and fatigue index) were assessed. The roles of Piezo1 were probed using the inhibitor GsMTx4 (a nonspecific mechanosensitive channel inhibitor) and adeno-associated virus (AAV)–mediated knockdown. Downstream signalling was identified by RNA sequencing (RNA-seq) and validated with cytosporone-B (CsnB, a specific agonist of Nr4a1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with controls, MV for 12 h induced significant diaphragm fibrosis, atrophy and dysfunction, alongside increased Piezo1 expression (mRNA: 2.362 ± 0.429 vs. 0.920 ± 0.363, <i>p</i> = 0.0018; protein: 1.098 ± 0.103 vs. 0.676 ± 0.102, <i>p</i> = 0.0007). Both GsMTx4 and Piezo1 knockdown alleviated these effects. Knockdown reduced the collagen deposition area by approximately 21% and downregulated key fibrotic markers including fibronectin (0.749 ± 0.118 vs. 1.081 ± 0.117, <i>p</i> < 0.0001), collagen 1 (0.703 ± 0.087 vs. 1.155 ± 0.131, <i>p</i> < 0.0001), collagen 3 (0.879 ± 0.074 vs. 1.063 ± 0.068, <i>p</i> = 0.022) and α-SMA (0.872 ± 0.657 vs. 1.108 ± 0.078, <i>p</i> = 0.0031) compared to the MV12 + shCtrl group. RNA-seq identified Nr4a1 as a downstream factor (<i>p</i> value < 0.009). CsnB treatment increased Nr4a1 expression (1.128 ± 0.113 vs. 0.490 ± 0.084, <i>p</i> < 0.0001), mitigating prolonged MV-induced diaphragm fibrosis and dysfunction but not atrophy (938.1 ± 116.2 vs. 754.7 ± 155.5, <i>p</i> = 0.1079).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Piezo1 upregulation is a key mechanism in ventilator-induced diaphragm fibrosis, potentially mediated through the Akt/Nr4a1 signalling pathway. Targeted inhibition of Piezo1 or activation of Nr4a1 presents a promising therapeutic strategy to prevent fibrosis and preserve diaphragm function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657067","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}
<p>We read with interest the comments by Du et al. [<span>1</span>] and Luo et al. [<span>2</span>] regarding our recent article ‘Impact of resistance training and chicken intake on vascular and muscle health in elderly women’ [<span>3</span>]. We are grateful for their thoughtful engagement with our study and their recognition of its contribution to understanding the effects of resistance training and high-protein intake on human muscle and artery health status. Their relevant observations offer an excellent opportunity to further discuss the challenges of muscle and artery health status in human research.</p><p>In this study, to examine the effects of the combination of resistance training and high-protein intake on the health status of aged muscles and arteries, we used a lot of materials and methods. Therefore, due to word count limitations, detailed descriptions of certain methods, such as ultrasound measurements of muscle thickness and echo intensity (EI), were provided in the Supplemental Materials and Methods. Separately, in this study, circulating creatinine levels were used as an index of renal function. No significant changes in circulating creatinine levels were observed before and after each intervention. Estimated glomerular filtration rate (eGFR) was analysed as an additional index of renal function (data not shown). The results showed no significant differences in eGFR before and after each intervention, and the percent changes in eGFR among the four groups were also not significant (Con: 5.0 ± 19.8%, HP: 6.1 ± 19.3%, RT: 1.6 ± 15.9%, HP + RT: −0.8 ± 24.2%), suggesting that these interventions did not affect renal function. Additionally, protein intake, as assessed by a questionnaire-based dietary survey, did not change significantly before and after each intervention, indicating no excessive protein intake during the study. Therefore, these results suggest that the intervention in this study did not adversely affect renal function.</p><p>Our primary outcomes focused on physiological indices of artery health, and we assessed circulating angiotensin II (Ang II) as one of the potential underlying mechanisms. The results indicated that changes in Ang II might partially explain the effects of high-protein diets on the increase in arterial stiffness induced by moderate to high-intensity resistance training. However, the activity and expression of angiotensin-converting enzyme (ACE) in arterial tissue were not assessed in this study, making it unclear whether Ang II alone could fully elucidate the underlying mechanism. Additionally, this study did not evaluate markers of oxidative stress and inflammation. Although circulating tumour necrosis factor-α (TNF-α) levels, a marker of inflammation, were measured, no significant changes before and after each intervention were observed among the four groups (data not shown in the manuscript). These findings suggest that the moderate to high-intensity resistance training protocol employed in this
我们饶有兴趣地阅读了Du et al.[1]和Luo et al. b[2]对我们最近的文章《抗阻训练和鸡肉摄入对老年妇女血管和肌肉健康的影响》的评论。我们非常感谢他们对我们研究的周到参与，以及他们对理解抗阻训练和高蛋白摄入对人体肌肉和动脉健康状况的影响的贡献。他们的相关观察为进一步讨论人类研究中肌肉和动脉健康状况的挑战提供了一个极好的机会。在本研究中，为了检验抗阻训练与高蛋白摄入相结合对老年肌肉和动脉健康状况的影响，我们使用了大量的材料和方法。因此，由于字数限制，在补充材料和方法中提供了某些方法的详细描述，例如超声测量肌肉厚度和回声强度（EI）。另外，在这项研究中，循环肌酐水平被用作肾功能的指标。在每次干预前后，循环肌酐水平均无明显变化。估计肾小球滤过率（eGFR）作为肾功能的附加指标进行分析（数据未显示）。结果显示，每次干预前后eGFR无显著差异，四组间eGFR百分比变化也无显著性差异（Con: 5.0±19.8%,HP: 6.1±19.3%,RT: 1.6±15.9%,HP + RT:−0.8±24.2%），提示干预对肾功能无影响。此外，通过一项基于问卷的饮食调查评估，蛋白质摄入量在每次干预前后没有显著变化，表明研究期间没有过量的蛋白质摄入。因此，这些结果表明本研究中的干预并未对肾功能产生不良影响。我们的主要结果集中在动脉健康的生理指标上，我们评估了循环血管紧张素II （Ang II）作为潜在的潜在机制之一。结果表明，Ang II的变化可能部分解释了高蛋白饮食对中高强度阻力训练引起的动脉僵硬增加的影响。然而，本研究未对动脉组织中血管紧张素转换酶（ACE）的活性和表达进行评估，因此尚不清楚仅Ang II能否完全阐明其潜在机制。此外，这项研究没有评估氧化应激和炎症的标志物。尽管测量了炎症标志物循环肿瘤坏死因子-α (TNF-α)水平，但在每次干预前后均未观察到四组患者的显著变化（数据未在论文中显示）。这些发现表明，本研究中采用的中高强度抗阻训练方案不会诱导全身性炎症。潜在的机制，包括氧化应激和炎症，不是本研究的重点，应该在未来的研究中探索。在我们的统计分析方法的研究中，我们选择了Bonferroni检验，因为四组之间的样本量的差异是由于磨耗造成的。此外，我们通过比较干预前后某些指标的值来评估效应量（数据未在手稿中显示），以评估研究结果的实际意义，而不仅仅是统计显著性。根据Cohen[4]，效应量分为小（d = 0.2）、中（d = 0.5）和大（d≥0.8）。在这项研究中，主要结果是血管和肌肉健康的测量，通过诸如颈动脉β-刚度（动脉刚度指数）、颈动脉-股动脉脉搏波速度（cfPWV；动脉刚度指数）、股四头肌横截面积（CSA；肌肉质量指数）和单次重复最大（1-RM）强度（肌肉力量指数）等指标进行评估。在本研究中，阻力训练（RT）组颈动脉β-僵硬度的效应量为1.0，表明中高强度的阻力训练增加了动脉僵硬度，而高蛋白摄入则减轻了这种增加，且效应量很大。相比之下，RT组cfPWV的效应量为0.2，表明影响较小。此外，阻力训练与高蛋白摄入（RT + HP）联合组四头肌CSA的效应量为0.81，表明效果较大。对于1-RM， RT组腿伸的效应量为1.55，RT + HP组为2.01，而RT组腿曲度的效应量为1.71，RT + HP组为1.69。这些发现表明，高蛋白摄入和中高强度阻力训练相结合可以增强血管和肌肉健康。总体而言，本研究中的大多数指标显示出较大的效应量。 我们的研究的主要发现是，对于老年人来说，结合中等到高强度的抗阻训练和定期摄入清蒸鸡胸肉作为高蛋白食物可能是一种新的运动和营养疗法。由于肌少症的诊断标准主要关注下肢肌肉功能和质量，因此改善下肢是降低肌少症风险的首要策略；因此，在本研究中，我们采用了针对下肢的阻力训练。然而，为了确保在现实环境中成功实施，强调设计个性化训练计划的重要性至关重要，该计划包括下肢和上肢锻炼，以优化个人结果。再次，我们很高兴我们的研究引起了同行的兴趣，我们真诚地感谢Du等人和Luo等人对我们工作的宝贵意见和关注。我们希望这封信将导致未来进一步的讨论和富有成果的交流。本研究由日本东京伊藤基金会（#134，M. Iemitsu）资助。本研究得到日本文部科学技术省科学研究资助（KAKENHI: 22H03487 for M. Iemitsu）。作者声明无利益冲突。
{"title":"Comments on ‘Impact of Resistance Training and Chicken Intake on Vascular and Muscle Health in Elderly Women’ by Du et al. and Luo et al. – The Authors' Reply","authors":"Shumpei Fujie, Naoki Horii, Hiroki Kajimoto, Henry Yamazaki, Kenichiro Inoue, Keiko Iemitsu, Masataka Uchida, Takuma Arimitsu, Yasushi Shinohara, Kiyoshi Sanada, Motohiko Miyachi, Motoyuki Iemitsu","doi":"10.1002/jcsm.70153","DOIUrl":"10.1002/jcsm.70153","url":null,"abstract":"<p>We read with interest the comments by Du et al. [<span>1</span>] and Luo et al. [<span>2</span>] regarding our recent article ‘Impact of resistance training and chicken intake on vascular and muscle health in elderly women’ [<span>3</span>]. We are grateful for their thoughtful engagement with our study and their recognition of its contribution to understanding the effects of resistance training and high-protein intake on human muscle and artery health status. Their relevant observations offer an excellent opportunity to further discuss the challenges of muscle and artery health status in human research.</p><p>In this study, to examine the effects of the combination of resistance training and high-protein intake on the health status of aged muscles and arteries, we used a lot of materials and methods. Therefore, due to word count limitations, detailed descriptions of certain methods, such as ultrasound measurements of muscle thickness and echo intensity (EI), were provided in the Supplemental Materials and Methods. Separately, in this study, circulating creatinine levels were used as an index of renal function. No significant changes in circulating creatinine levels were observed before and after each intervention. Estimated glomerular filtration rate (eGFR) was analysed as an additional index of renal function (data not shown). The results showed no significant differences in eGFR before and after each intervention, and the percent changes in eGFR among the four groups were also not significant (Con: 5.0 ± 19.8%, HP: 6.1 ± 19.3%, RT: 1.6 ± 15.9%, HP + RT: −0.8 ± 24.2%), suggesting that these interventions did not affect renal function. Additionally, protein intake, as assessed by a questionnaire-based dietary survey, did not change significantly before and after each intervention, indicating no excessive protein intake during the study. Therefore, these results suggest that the intervention in this study did not adversely affect renal function.</p><p>Our primary outcomes focused on physiological indices of artery health, and we assessed circulating angiotensin II (Ang II) as one of the potential underlying mechanisms. The results indicated that changes in Ang II might partially explain the effects of high-protein diets on the increase in arterial stiffness induced by moderate to high-intensity resistance training. However, the activity and expression of angiotensin-converting enzyme (ACE) in arterial tissue were not assessed in this study, making it unclear whether Ang II alone could fully elucidate the underlying mechanism. Additionally, this study did not evaluate markers of oxidative stress and inflammation. Although circulating tumour necrosis factor-α (TNF-α) levels, a marker of inflammation, were measured, no significant changes before and after each intervention were observed among the four groups (data not shown in the manuscript). These findings suggest that the moderate to high-intensity resistance training protocol employed in this","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12669905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653233","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}
<p>We appreciate the authors' interest in our work on the relationship between adherence to physical activity interventions and the prevention of mobility disability. We are grateful for the critical insights they have provided, which highlight important methodological and clinical aspects that warrant consideration when assessing adherence and dose–response relationships.</p><p>The arguments raised by Zhang and Zhang [<span>1</span>] align with ongoing discussions in the field about refining trial designs to better capture the multifaceted and complex nature of physical activity interventions, particularly in older adults with mobility limitations. Regarding the potential confounding effect whereby participants with better baseline health or higher fitness levels may demonstrate greater adherence, we acknowledge this as a valid concern, since it could introduce selection bias into subgroup analyses. In our analyses, however, we attempted to account for key variables that could influence the results (i.e., age, sex, BMI, medical conditions, SPPB, MMSE, CES-D and SARC-F) [<span>2</span>], thereby reducing the impact of baseline subgroup traits. We also recognise that our study is inherently limited by the absence of other relevant factors (e.g., polypharmacy, personal motivation, fear of fatigue, social support and weather conditions) [<span>3</span>]. Future research exploring these and other variables will help optimise the prescription of physical activity for older adults and identify strategies to enhance adherence.</p><p>The suggestion to incorporate wearable sensors such as accelerometers, pedometers and heart rate monitors to establish comprehensive dose profiles is promising. However, in clinical practice and large multicentre trials, the use of such devices remains challenging. Indeed, the SPRINTT trial attempted to integrate a sensor-based approach [<span>4</span>], but feasibility issues limited its implementation across all centres. Nevertheless, such tools may prove essential for exploring isotemporal substitution analyses, as proposed, and will hopefully be incorporated into future trials to better evaluate both supervised and unsupervised activity, thereby defining objective thresholds of frequency, intensity and type of exercise associated with mobility outcomes in this population.</p><p>The development of composite indexes that integrate attendance with intensity and duration is another interesting avenue. We agree that such scores, potentially weighted by moderate-to-vigorous physical activity, session bout length and perceived exertion, should be validated against clinical endpoints to ensure predictive value. It is important to note, however, that heart rate can provide biased estimates of resistance exercise intensity, particularly in older adults who are frequently prescribed medications (e.g., beta-blockers, calcium channel blockers and anti-arrhythmics) that alter cardiovascular responses. Moreover, in practical terms, mon
{"title":"Comment on ‘Adherence to Physical Activity and Incident Mobility Disability in Older Adults With Mobility Limitations’ by Alvarez-Bustos et al.: The Authors' Reply","authors":"Alejandro Álvarez-Bustos, Emanuele Marzetti","doi":"10.1002/jcsm.70148","DOIUrl":"10.1002/jcsm.70148","url":null,"abstract":"<p>We appreciate the authors' interest in our work on the relationship between adherence to physical activity interventions and the prevention of mobility disability. We are grateful for the critical insights they have provided, which highlight important methodological and clinical aspects that warrant consideration when assessing adherence and dose–response relationships.</p><p>The arguments raised by Zhang and Zhang [<span>1</span>] align with ongoing discussions in the field about refining trial designs to better capture the multifaceted and complex nature of physical activity interventions, particularly in older adults with mobility limitations. Regarding the potential confounding effect whereby participants with better baseline health or higher fitness levels may demonstrate greater adherence, we acknowledge this as a valid concern, since it could introduce selection bias into subgroup analyses. In our analyses, however, we attempted to account for key variables that could influence the results (i.e., age, sex, BMI, medical conditions, SPPB, MMSE, CES-D and SARC-F) [<span>2</span>], thereby reducing the impact of baseline subgroup traits. We also recognise that our study is inherently limited by the absence of other relevant factors (e.g., polypharmacy, personal motivation, fear of fatigue, social support and weather conditions) [<span>3</span>]. Future research exploring these and other variables will help optimise the prescription of physical activity for older adults and identify strategies to enhance adherence.</p><p>The suggestion to incorporate wearable sensors such as accelerometers, pedometers and heart rate monitors to establish comprehensive dose profiles is promising. However, in clinical practice and large multicentre trials, the use of such devices remains challenging. Indeed, the SPRINTT trial attempted to integrate a sensor-based approach [<span>4</span>], but feasibility issues limited its implementation across all centres. Nevertheless, such tools may prove essential for exploring isotemporal substitution analyses, as proposed, and will hopefully be incorporated into future trials to better evaluate both supervised and unsupervised activity, thereby defining objective thresholds of frequency, intensity and type of exercise associated with mobility outcomes in this population.</p><p>The development of composite indexes that integrate attendance with intensity and duration is another interesting avenue. We agree that such scores, potentially weighted by moderate-to-vigorous physical activity, session bout length and perceived exertion, should be validated against clinical endpoints to ensure predictive value. It is important to note, however, that heart rate can provide biased estimates of resistance exercise intensity, particularly in older adults who are frequently prescribed medications (e.g., beta-blockers, calcium channel blockers and anti-arrhythmics) that alter cardiovascular responses. Moreover, in practical terms, mon","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651590","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}
Clemens Metze, Elric Zweck, Christos Iliadis, Maria Isabel Körber, Matthieu Schäfer, Ralf Westenfeld, Amin Polzin, Marcel Halbach, Stephan Baldus, Roman Pfister
Objective
The aim of this study was to examine frailty measures for risk prediction in patients undergoing percutaneous mitral valve repair (PMVR).
Background
Performance of current risk prediction models based on organ morbidity is only moderate.
Methods
The frailty domains exhaustion, slowness, inactivity, weakness, and unintentional weight loss were prospectively assessed in patients undergoing PMVR. The association with mortality and heart failure hospitalization (HFH) during a median follow-up of 506 days was examined and relevant domains were assessed for additive predictive performance over the MitraScore.
Results
Five hundred twenty-four patients were included in the study (mean age [SD]: 77 (9) years, 54.6% male). The risk of mortality and mortality/HFH were significantly increased in patients with exhaustion (hazard ratio: 2.24 [95% CI: 1.63–3.08]/1.83 [1.21–2.77]), slowness (2.74 [1.75–4.30]/1.92 [1.34–2.75]), inactivity (1.96 [1.26–3.05]/1.61 [1.12–2.31]) and weakness (1.83 [1.12–2.96]/1.34 [0.92–1.95]), but not in patients with weight loss (1.24 [0.80–1.92]/1.12 [0.78–1.61]). A simplified frailty (S-frailty) measure derived from the domains exhaustion and slowness was associated with mortality (4.45 [2.42–8.19]) and mortality/HFH (2.60 [1.64–4.13]) independently of clinical risk factors and the MitraScore, respectively. Prediction of mortality by the MitraScore was significantly improved when adding S-frailty (Harrell's C 0.645 vs. 0.700, p = 0.002). Classification of 1-year mortality risk by the MitraScore improved when adding S-frailty (net reclassification index 0.21, p = 0.012 and integrated discrimination index 0.07, p < 0.001).
Conclusions
A simplified frailty measure comprising self-reported exhaustion and gait speed significantly improved risk prediction in patients undergoing PMVR. Assessment of frailty measures should be part of the decision-making process and multiparametric risk scores in patients with severe mitral regurgitation.
目的：本研究的目的是研究衰弱指标对经皮二尖瓣修复（PMVR）患者的风险预测。背景：目前基于器官发病率的风险预测模型的性能仅为中等。方法：前瞻性评估PMVR患者的衰弱域衰竭、迟缓、不活动、虚弱和意外体重减轻。在中位506天的随访期间，研究了与死亡率和心力衰竭住院（HFH）的关联，并评估了MitraScore的相关域的附加预测性能。结果：524例患者纳入研究，平均年龄[SD]: 77(9)岁，男性54.6%。衰竭（风险比：2.24 [95% CI: 1.63-3.08]/1.83[1.21-2.77]）、行动迟缓（风险比：2.74[1.75-4.30]/1.92[1.34-2.75]）、不活动（风险比：1.96[1.26-3.05]/1.61[1.12-2.31]）和虚弱（风险比：1.83[1.12-2.96]/1.34[0.92-1.95]）患者的死亡率和死亡率/HFH显著增加，体重减轻（风险比：1.24[0.80-1.92]/1.12[0.78-1.61]）患者的死亡率和死亡率/HFH显著增加。从结构域耗尽和缓慢得到的简化虚弱（s -脆弱）测量分别与死亡率（4.45[2.42-8.19]）和死亡率/HFH（2.60[1.64-4.13]）相关，独立于临床危险因素和MitraScore。加入s -脆弱性后，MitraScore对死亡率的预测显著提高（Harrell’s C = 0.645 vs. 0.700, p = 0.002）。加入s -衰弱（净重分类指数0.21,p = 0.012，综合区分指数0.07,p）后，MitraScore对1年死亡风险的分类得到改善。结论：一种简化的衰弱测量方法，包括自我报告的疲劳和步态速度，可显著提高PMVR患者的风险预测。对于严重二尖瓣反流患者，虚弱措施的评估应该是决策过程和多参数风险评分的一部分。
{"title":"A Simplified Frailty Measure Improves Risk Stratification in Patients Undergoing Percutaneous Mitral Valve Repair","authors":"Clemens Metze, Elric Zweck, Christos Iliadis, Maria Isabel Körber, Matthieu Schäfer, Ralf Westenfeld, Amin Polzin, Marcel Halbach, Stephan Baldus, Roman Pfister","doi":"10.1002/jcsm.70138","DOIUrl":"10.1002/jcsm.70138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to examine frailty measures for risk prediction in patients undergoing percutaneous mitral valve repair (PMVR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Performance of current risk prediction models based on organ morbidity is only moderate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The frailty domains exhaustion, slowness, inactivity, weakness, and unintentional weight loss were prospectively assessed in patients undergoing PMVR. The association with mortality and heart failure hospitalization (HFH) during a median follow-up of 506 days was examined and relevant domains were assessed for additive predictive performance over the MitraScore.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five hundred twenty-four patients were included in the study (mean age [SD]: 77 (9) years, 54.6% male). The risk of mortality and mortality/HFH were significantly increased in patients with exhaustion (hazard ratio: 2.24 [95% CI: 1.63–3.08]/1.83 [1.21–2.77]), slowness (2.74 [1.75–4.30]/1.92 [1.34–2.75]), inactivity (1.96 [1.26–3.05]/1.61 [1.12–2.31]) and weakness (1.83 [1.12–2.96]/1.34 [0.92–1.95]), but not in patients with weight loss (1.24 [0.80–1.92]/1.12 [0.78–1.61]). A simplified frailty (S-frailty) measure derived from the domains exhaustion and slowness was associated with mortality (4.45 [2.42–8.19]) and mortality/HFH (2.60 [1.64–4.13]) independently of clinical risk factors and the MitraScore, respectively. Prediction of mortality by the MitraScore was significantly improved when adding S-frailty (Harrell's C 0.645 vs. 0.700, <i>p</i> = 0.002). Classification of 1-year mortality risk by the MitraScore improved when adding S-frailty (net reclassification index 0.21, <i>p</i> = 0.012 and integrated discrimination index 0.07, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A simplified frailty measure comprising self-reported exhaustion and gait speed significantly improved risk prediction in patients undergoing PMVR. Assessment of frailty measures should be part of the decision-making process and multiparametric risk scores in patients with severe mitral regurgitation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12668899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653255","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}
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