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Evaluation of the prognostic value of computed tomography-derived body composition in patients undergoing endovascular aneurysm repair 对行血管内动脉瘤修复术患者的ct体成分预测价值的评价
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-23 DOI: 10.1002/jcsm.13262
Nicholas A. Bradley, Amy Walter, Ross Dolan, Alasdair Wilson, Tamim Siddiqui, Campbell S.D. Roxburgh, Donald C. McMillan, Graeme J.K. Guthrie

Background

Endovascular aneurysm repair (EVAR) is the most common mode of repair of abdominal aortic aneurysms (AAA) in the UK. EVAR ranges from standard infrarenal repair to complex fenestrated and branched EVAR (F/B-EVAR). Sarcopenia is defined by lower muscle mass and function, which is associated with inferior perioperative outcomes. Computed tomography-derived body composition analysis offers prognostic value in patients with cancer. Several authors have evaluated the role of body composition analysis in predicting outcomes in patients undergoing EVAR; however, the evidence base is limited by heterogeneous methodology.

Methods

Six hundred seventy-four consecutive patients (58 (8.6%) female, mean (SD) age 74.4 (6.8) years) undergoing EVAR and F/B-EVAR at three large tertiary centres were retrospectively recruited. Subcutaneous and visceral fat indices (SFI and VFI), psoas and skeletal muscle indices, and skeletal muscle density were measured at the L3 vertebral level from pre-operative computed tomographies. The maximally selected rank statistic technique was used to define optimal thresholds to predict mortality.

Results

There were 191 deaths during the median follow-up period of 60.0 months. Mean (95% CI) survival in the low SMI versus high SMI subgroups was 62.6 (58.5–66.7) versus 82.0 (78.7–85.3) months (P < 0.001). Mean (95% CI) survival in the low SFI versus high SFI subgroups was 56.4 (48.2–64.7) versus 77.1 (74.2–80.1) months (P < 0.001). One-year mortality in the low SMI versus high SMI subgroups was 10% versus 3% (P < 0.001). Low SMI was associated with increased odds of one-year mortality (OR 3.19, 95% CI 1.60–6.34, P < 0.001). Five-year mortality in the low SMI versus high SMI subgroups was 55% versus 28% (P < 0.001). Low SMI was associated with increased odds of five-year mortality (OR 1.54, 95% CI 1.11–2.14, P < 0.01). On multivariate analysis of all patients, low SFI (HR 1.90, 95% CI 1.30–2.76, P < 0.001) and low SMI (HR 1.88, 95% CI 1.34–2.63, P < 0.001) were associated with poorer survival. On multivariate analysis of asymptomatic AAA patients, low SFI (HR 1.54, 95% CI 1.01–2.35, P < 0.05) and low SMI (HR 1.71, 95% CI 1.20–2.42, P < 0.01) were associated with poorer survival.

Conclusions

Low SMI and SFI are associated with poorer long-term survival following EVAR and F/B-EVAR. The relation

在英国，血管内动脉瘤修复(EVAR)是腹主动脉瘤(AAA)最常见的修复方式。EVAR的范围从标准的肾下修复到复杂的开窗和分支EVAR (F/B-EVAR)。肌肉减少症的定义是肌肉质量和功能降低，这与围手术期预后较差有关。计算机断层扫描衍生的身体成分分析为癌症患者的预后提供了价值。几位作者评估了体成分分析在预测EVAR患者预后中的作用;然而，证据基础受到异质性方法的限制。方法回顾性招募674例连续患者，其中58例(8.6%)为女性，平均(SD)年龄74.4(6.8)岁，在三个大型三级中心接受EVAR和F/B-EVAR。术前计算机断层扫描在L3椎体水平测量皮下和内脏脂肪指数(SFI和VFI)、腰肌和骨骼肌指数以及骨骼肌密度。采用最大选择秩统计技术确定预测死亡率的最佳阈值。结果中位随访60.0个月，死亡191例。低重度精神障碍亚组和高重度精神障碍亚组的平均(95% CI)生存期分别为62.6(58.5-66.7)和82.0(78.7-85.3)个月(P <0.001)。低SFI亚组和高SFI亚组的平均(95% CI)生存期分别为56.4(48.2-64.7)和77.1(74.2-80.1)个月(P <0.001)。低重度精神障碍亚组和高重度精神障碍亚组的1年死亡率分别为10%和3% (P <0.001)。低SMI与一年死亡率增加相关(OR 3.19, 95% CI 1.60-6.34, P <0.001)。低重度精神障碍亚组和高重度精神障碍亚组的5年死亡率分别为55%和28% (P <0.001)。低SMI与5年死亡率增加相关(OR 1.54, 95% CI 1.11-2.14, P <0.01)。在所有患者的多变量分析中，低SFI (HR 1.90, 95% CI 1.30-2.76, P <0.001)和低SMI (HR 1.88, 95% CI 1.34-2.63, P <0.001)与较差的生存率相关。无症状AAA患者的多因素分析，低SFI (HR 1.54, 95% CI 1.01-2.35, P <0.05)和低SMI (HR 1.71, 95% CI 1.20-2.42, P <0.01)与较差的生存率相关。结论:低SMI和SFI与EVAR和F/B-EVAR后较差的长期生存相关。体成分与预后的关系需要进一步评估，并需要对AAA患者提出的阈值进行外部验证。
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引用次数: 1
Five-year follow-up study on quantitative muscle magnetic resonance imaging in facioscapulohumeral muscular dystrophy: The link to clinical outcome 面肩肱骨肌营养不良定量肌肉磁共振成像的五年随访研究:与临床结果的联系
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-23 DOI: 10.1002/jcsm.13250
Sanne C.C. Vincenten, Karlien Mul, Dani?l van As, Julia J. Jansen, Linda Heskamp, Arend Heerschap, Baziel G.M. van Engelen, Nicol C. Voermans

Background

It is unclear how changes in quantitative muscle magnetic resonance imaging (MRI) relate to changes in clinical outcome in facioscapulohumeral muscular dystrophy (FSHD), although this information is crucial for optimal use of MRI as imaging biomarker in trials. We therefore assessed muscle MRI and clinical outcome measures in a large longitudinal prospective cohort study.

Methods

All patients were assessed by MRI at baseline and at 5-year follow-up, employing 2pt-Dixon and turbo inversion recovery magnitude (TIRM) sequences, after which fat fraction and TIRM positivity of 19 leg muscles were determined bilaterally. The MRI compound score (CoS) was defined as the mean fat fraction of all muscles weighted for cross-sectional area. Clinical outcome measures included the Ricci-score, FSHD clinical score (FSHD-CS), MRC sumscore (MRC-SS), and motor-function-measure (MFM).

Results

We included 105 FSHD patients [mean age 54 ± 14 years, median Ricci-score 7 (range 0–10)]. The median change over 5 years' time in the MRI-CoS was 2.0% (range −4.6 to +12.1; P < 0.001). The median change over 5 years' time in clinical outcome measures was small in all measures, with z-scores ranging from 5.0 to 7.2 (P < 0.001). The change in MRI-CoS correlated with change in FSHD-CS and Ricci-score (ρ = 0.25, respectively; ρ = 0.23, P < 0.05). The largest median increase in MRI-CoS was seen in baseline subgroups with an MRI-CoS 20–40% (6.1%), with ≥2 TIRM positive muscles (3.5%) or with an FSHD-CS 5–10 (3.1%).

Conclusions

This 5-year study showed significant changes in MRI and clinical outcome measures and a significant correlation between changes in MRI-CoS and changes in clinical outcome measures. In addition, we identified subgroups of patients that are most prone to radiological disease progression. This knowledge further establishes quantitative MRI parameters as prognostic biomarkers in FSHD and as efficacy biomarkers in upcoming clinical trials.

目前尚不清楚定量肌肉磁共振成像(MRI)的变化与面肩肱肌营养不良症(FSHD)临床结果的变化之间的关系，尽管这一信息对于在试验中优化使用MRI作为成像生物标志物至关重要。因此，我们在一项大型纵向前瞻性队列研究中评估了肌肉MRI和临床结果测量。方法对所有患者在基线和5年随访时进行MRI评估，采用2pt-Dixon和涡轮反转恢复幅度(TIRM)序列，随后测定19块腿部肌肉的脂肪含量和TIRM阳性。MRI复合评分(CoS)定义为横截面积加权后所有肌肉的平均脂肪分数。临床结果测量包括ricci评分、FSHD临床评分(FSHD- cs)、MRC评分(MRC- ss)和运动功能测量(MFM)。结果纳入105例FSHD患者[平均年龄54±14岁，ricci评分中位数为7(范围0-10)]。5年内MRI-CoS的中位变化为2.0%(范围为- 4.6至+12.1;P & lt;0.001)。5年临床结果测量的中位变化在所有测量中都很小，z分数范围为5.0至7.2 (P <0.001)。MRI-CoS的变化与FSHD-CS和ricci评分的变化相关(ρ = 0.25;ρ = 0.23, P <0.05)。MRI-CoS中位数增加最大的是基线亚组，MRI-CoS为20-40%(6.1%)，≥2块TIRM阳性肌肉(3.5%)或FSHD-CS为5-10(3.1%)。结论这项为期5年的研究显示，MRI和临床结果指标发生了显著变化，MRI- cos的变化与临床结果指标的变化之间存在显著相关性。此外，我们确定了最容易发生放射学疾病进展的患者亚组。这些知识进一步确立了定量MRI参数作为FSHD的预后生物标志物和即将进行的临床试验的疗效生物标志物。
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引用次数: 1
Validation of a telephone-based administration of the simplified nutritional appetite questionnaire 简化营养食欲问卷电话管理的验证
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-22 DOI: 10.1002/jcsm.13264
Binh Duong Thai, Jürgen M. Bauer, Annette Eidam, Jane Durga, Stefan Grund, Thomas Mross, Petra Benzinger

Background

Anorexia of aging is characterized by an age-associated reduction of appetite, whose aetiology in most cases is multifactorial and which often triggers malnutrition. The Simplified Nutritional Appetite Questionnaire (SNAQ) is an established screening tool. This study aimed to investigate reliability, validity, and feasibility of its telephone administration (T-SNAQ) in German community-dwelling older adults.

Methods

This cross-sectional single-centre study recruited participants from April 2021 to September 2021. First, the SNAQ was translated into German according to an established methodology. After translation, reliability, construct validity, and feasibility of the T-SNAQ were analysed. A convenience sample of community-dwelling older adults aged ≥70 years was recruited. The following measurements were applied to all participants: T-SNAQ, Mini Nutritional Assessment – Short Form (MNA-SF), six-item Katz index of independence in activities of daily living (ADL), eight-item Lawton instrumental activities of daily living (IADL), telephone Montreal Cognitive Assessment (T-MoCA); FRAIL scale, Geriatric Depression Scale (GDS-15) and Charlson co-morbidity index as well as daily caloric and protein intake.

Results

One hundred twenty participants (59.2% female) with a mean age of 78.0 ± 5.8 years were included in the present study. The percentage of participants identified with poor appetite based on T-SNAQ was 20.8% (n = 25). T-SNAQ showed a good internal reliability with a Cronbach's alpha coefficient of 0.64 and a good test–retest reliability [intraclass coefficient of 0.95 (P < 0.05)]. Regarding construct validity, T-SNAQ was significantly positively correlated with MNA-SF (r = 0.213), T-MoCA (r = 0.225), daily energy (r = 0.222) and protein intake (r = 0.252) (P < 0.05). It also demonstrated a significant negative association with GDS-15 (r = −0.361), FRAIL scale (r = −0.203) and Charlson co-morbidity index (r = −0.272). Regarding applicability, the mean time for T-SNAQ was 95 s and completion rate was 100%.

Conclusions

The T-SNAQ is a feasible screening instrument for anorexia of aging in community-dwelling older adults via telephone interviews.

背景:老年厌食症的特点是与年龄相关的食欲下降，其病因在大多数情况下是多因素的，并经常引发营养不良。简易营养食欲问卷(SNAQ)是一种成熟的筛查工具。本研究旨在探讨德国社区老年人电话管理(T-SNAQ)的信度、效度和可行性。方法本横断面单中心研究于2021年4月至2021年9月招募参与者。首先，按照既定的方法将SNAQ翻译成德语。翻译后，对T-SNAQ的信度、结构效度和可行性进行了分析。招募了≥70岁的社区居住老年人作为方便样本。所有被试均采用以下测量方法:T-SNAQ、Mini nutrition Assessment - Short Form (MNA-SF)、6项Katz日常生活活动独立性指数(ADL)、8项Lawton工具性日常生活活动(IADL)、电话蒙特利尔认知评估(T-MoCA);虚弱量表、老年抑郁量表(GDS-15)和Charlson共发病指数以及每日热量和蛋白质摄入量。结果共纳入120例患者，其中女性59.2%，平均年龄78.0±5.8岁。根据T-SNAQ被确定为胃口不好的参与者的百分比为20.8% (n = 25)。T-SNAQ具有良好的内部信度，Cronbach's alpha系数为0.64，重测信度为0.95 (P <0.05)]。在构效度方面，T-SNAQ与MNA-SF (r = 0.213)、T-MoCA (r = 0.225)、日能量(r = 0.222)和蛋白质摄入量(r = 0.252)呈显著正相关(P <0.05)。与GDS-15 (r = - 0.361)、虚弱量表(r = - 0.203)和Charlson共发病指数(r = - 0.272)呈显著负相关。在适用性方面，T-SNAQ的平均时间为95 s，完成率为100%。结论T-SNAQ是一种可行的电话访谈老年厌食症筛查工具。
{"title":"Validation of a telephone-based administration of the simplified nutritional appetite questionnaire","authors":"Binh Duong Thai,&nbsp;Jürgen M. Bauer,&nbsp;Annette Eidam,&nbsp;Jane Durga,&nbsp;Stefan Grund,&nbsp;Thomas Mross,&nbsp;Petra Benzinger","doi":"10.1002/jcsm.13264","DOIUrl":"https://doi.org/10.1002/jcsm.13264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anorexia of aging is characterized by an age-associated reduction of appetite, whose aetiology in most cases is multifactorial and which often triggers malnutrition. The Simplified Nutritional Appetite Questionnaire (SNAQ) is an established screening tool. This study aimed to investigate reliability, validity, and feasibility of its telephone administration (T-SNAQ) in German community-dwelling older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional single-centre study recruited participants from April 2021 to September 2021. First, the SNAQ was translated into German according to an established methodology. After translation, reliability, construct validity, and feasibility of the T-SNAQ were analysed. A convenience sample of community-dwelling older adults aged ≥70 years was recruited. The following measurements were applied to all participants: T-SNAQ, Mini Nutritional Assessment – Short Form (MNA-SF), six-item Katz index of independence in activities of daily living (ADL), eight-item Lawton instrumental activities of daily living (IADL), telephone Montreal Cognitive Assessment (T-MoCA); FRAIL scale, Geriatric Depression Scale (GDS-15) and Charlson co-morbidity index as well as daily caloric and protein intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred twenty participants (59.2% female) with a mean age of 78.0 ± 5.8 years were included in the present study. The percentage of participants identified with poor appetite based on T-SNAQ was 20.8% (<i>n</i> = 25). T-SNAQ showed a good internal reliability with a Cronbach's alpha coefficient of 0.64 and a good test–retest reliability [intraclass coefficient of 0.95 (<i>P</i> &lt; 0.05)]. Regarding construct validity, T-SNAQ was significantly positively correlated with MNA-SF (<i>r</i> = 0.213), T-MoCA (<i>r</i> = 0.225), daily energy (<i>r</i> = 0.222) and protein intake (<i>r</i> = 0.252) (<i>P</i> &lt; 0.05). It also demonstrated a significant negative association with GDS-15 (<i>r</i> = −0.361), FRAIL scale (<i>r</i> = −0.203) and Charlson co-morbidity index (<i>r</i> = −0.272). Regarding applicability, the mean time for T-SNAQ was 95 s and completion rate was 100%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The T-SNAQ is a feasible screening instrument for anorexia of aging in community-dwelling older adults via telephone interviews.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1848-1854"},"PeriodicalIF":8.9,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5753608","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}
引用次数: 0
Low muscle mass, malnutrition, sarcopenia, and associations with survival in adults with cancer in the UK Biobank cohort 在英国生物银行队列中，低肌肉量、营养不良、肌肉减少症与成人癌症患者生存率的关系
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-22 DOI: 10.1002/jcsm.13256
Nicole Kiss, Carla M. Prado, Robin M. Daly, Linda Denehy, Lara Edbrooke, Brenton J. Baguley, Steve F. Fraser, Abbas Khosravi, Gavin Abbott

Background

Low muscle mass (MM) is a common component of cancer-related malnutrition and sarcopenia, conditions that are all independently associated with an increased risk of mortality. This study aimed to (1) compare the prevalence of low MM, malnutrition, and sarcopenia and their association with survival in adults with cancer from the UK Biobank and (2) explore the influence of different allometric scaling (height [m2] or body mass index [BMI]) on low MM estimates.

Methods

Participants in the UK Biobank with a cancer diagnosis within 2 years of the baseline assessment were identified. Low MM was estimated by appendicular lean soft tissue (ALST) from bioelectrical impedance analysis derived fat-free mass. Malnutrition was determined using the Global Leadership in Malnutrition criteria. Sarcopenia was defined using the European Working Group on Sarcopenia in Older People criteria (version 2). All-cause mortality was determined from linked national mortality records. Cox-proportional hazards models were fitted to estimate the effect of low MM, malnutrition, and sarcopenia on all-cause mortality.

Results

In total, 4122 adults with cancer (59.8 ± 7.1 years; 49.2% male) were included. Prevalence of low MM (8.0% vs. 1.7%), malnutrition (11.2% vs. 6.2%), and sarcopenia (1.4% vs. 0.2%) was higher when MM was adjusted using ALST/BMI compared with ALST/height2, respectively. Low MM using ALST/BMI identified more cases in participants with obesity (low MM 56.3% vs. 0%; malnutrition 50% vs. 18.5%; sarcopenia 50% vs. 0%). During a median 11.2 (interquartile range: 10.2, 12.0) years of follow up, 901 (21.7%) of the 4122 participants died, and of these, 744 (82.6%) deaths were cancer-specific All conditions were associated with a higher hazard of mortality using either method of MM adjustment: low MM (ALST/height2: HR 1.9 [95% CI 1.3, 2.8], P = 0.001; ALST/BMI: HR 1.3 [95% CI 1.1, 1.7], P = 0.005; malnutrition (ALST/height2: HR 2.5 [95% CI 1.1, 1.7], P = 0.005; ALST/BMI: HR 1.3 [95% CI 1.1, 1.7], P = 0.005; sarcopenia (ALST/height2: HR 2.9 [95% CI 1.3, 6.5], P = 0.013; ALST/BMI: HR 1.6 [95% CI 1.0, 2.4], P = 0.037).

Conclusions

In adults with cancer, malnutrition was more common than low MM or sarcopenia, although all conditions were associated with a higher mortality risk, regardless of the method of adjusting for MM. In co

背景:低肌肉质量(MM)是癌症相关营养不良和肌肉减少症的常见组成部分，这些疾病都与死亡风险增加独立相关。本研究旨在(1)比较来自英国生物银行(UK Biobank)的成人癌症患者中低MM、营养不良和肌肉减少症的患病率及其与生存率的关系;(2)探索不同异速测量尺度(身高[m2]或体重指数[BMI])对低MM估计的影响。方法在基线评估后2年内被诊断为癌症的英国生物银行参与者被确定。通过生物电阻抗分析得出无脂质量，通过阑尾瘦软组织(ALST)估计低MM。营养不良是根据全球营养不良领导标准确定的。肌少症的定义采用欧洲老年人肌少症工作组标准(版本2)。全因死亡率根据相关的国家死亡率记录确定。拟合cox比例风险模型来估计低MM、营养不良和肌肉减少症对全因死亡率的影响。结果共4122例成人肿瘤患者(59.8±7.1岁;49.2%为男性)。当分别使用ALST/BMI与ALST/身高2调整MM时，低MM(8.0%对1.7%)、营养不良(11.2%对6.2%)和肌肉减少症(1.4%对0.2%)的患病率更高。低MM使用ALST/BMI识别出更多的肥胖病例(低MM 56.3%对0%;营养不良50% vs. 18.5%;肌肉减少50% vs. 0%)。在中位随访11.2年(四分位数间距:10.2,12.0)期间，4122名参与者中有901人(21.7%)死亡，其中744人(82.6%)死亡是癌症特异性死亡。使用MM调整的任何一种方法，所有疾病都与较高的死亡风险相关:低MM (ALST/height2: HR 1.9 [95% CI 1.3, 2.8]， P = 0.001;Alst / bmi: hr 1.3 [95% ci 1.1, 1.7]， p = 0.005;营养不良(ALST/ high2: HR 2.5 [95% CI 1.1, 1.7]， P = 0.005;Alst / bmi: hr 1.3 [95% ci 1.1, 1.7]， p = 0.005;肌肉减少症(ALST/height2: HR 2.9 [95% CI 1.3, 6.5]， P = 0.013;Alst / bmi: hr 1.6 [95% ci 1.0, 2.4]， p = 0.037]。结论:在成年癌症患者中，营养不良比低MM或肌肉减少症更常见，尽管所有情况都与更高的死亡风险相关，无论MM调整方法如何。相反，与身高调整相比，BMI调整低MM发现了更多的低MM、营养不良和肌肉减少症的病例，并且在肥胖的参与者中，这表明它是首选的调整。
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引用次数: 1
Slo1 deficiency impaired skeletal muscle regeneration and slow-twitch fibre formation Slo1缺乏损害骨骼肌再生和慢肌纤维形成
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-22 DOI: 10.1002/jcsm.13253
Chao Xia, Yonghui Wang, Tianyuan Jiang, Yan Hu, Yang Chen, Xinrun Ma, Xuemei Zhang, Yanhong Gao

Background

It has been observed that Slo1 knockout mice have reduced motor function, and people with certain Slo1 mutations have movement problems, but there is no answer whether the movement disorder is caused by the loss of Slo1 in the nervous system, or skeletal muscle, or both. Here, to ascertain in which tissues Slo1 functions to regulate motor function and offer deeper insight in treating related movement disorder, we generated skeletal muscle-specific Slo1 knockout mice, studied the functional changes in Slo1-deficient skeletal muscle and explored the underlying mechanism.

Methods

We used skeletal muscle-specific Slo1 knockout mice (Myf5-Cre; Slo1flox/flox mice, called CKO) as in vivo models to examine the role of Slo1 in muscle growth and muscle regeneration. The forelimb grip strength test was used to assess skeletal muscle function and treadmill exhaustion test was used to test whole-body endurance. Mouse primary myoblasts derived from CKO (myoblast/CKO) mice were used to extend the findings to in vitro effects on myoblast differentiation and fusion. Quantitative real-time PCR, western blot and immunofluorescence approaches were used to analyse Slo1 expression during myoblast differentiation and muscle regeneration. To investigate the involvement of genes in the regulation of muscle dysfunction induced by Slo1 deletion, RNA-seq analysis was performed in primary myoblasts. Immunoprecipitation and mass spectrometry were used to identify the protein interacting with Slo1. A dual-luciferase reporter assay was used to identify whether Slo1 deletion affects NFAT activity.

Results

We found that the body weight and size of CKO mice were not significantly different from those of Slo1flox/flox mice (called WT). Deficiency of Slo1 in muscles leads to reduced endurance (~30% reduction, P < 0.05) and strength (~30% reduction, P < 0.001). Although there was no difference in the general morphology of the muscles, electron microscopy revealed a considerable reduction in the content of mitochondria in the soleus muscle (~40% reduction, P < 0.01). We found that Slo1 was expressed mainly on the cell membrane and showed higher expression in slow-twitch fibres. Slo1 protein expression is progressively reduced during muscle postnatal development and regeneration after injury, and the expression is strongly reduced during myoblast differentiation. Slo1 deletion impaired myoblast differentiation and slow-twitch fibre formation. Mechanistically, RNA-seq analysis showed that Slo1 influences the expression of g

研究发现，Slo1基因敲除小鼠的运动功能会下降，而Slo1基因突变的人会出现运动问题，但这种运动障碍是由神经系统、骨骼肌或两者中Slo1基因的缺失引起的，目前还没有答案。为了确定Slo1在哪些组织中起调节运动功能的作用，并为治疗相关运动障碍提供更深入的见解，我们制造了骨骼肌特异性Slo1基因敲除小鼠，研究了Slo1缺失骨骼肌的功能变化，并探讨了其潜在机制。方法采用骨骼肌特异性Slo1敲除小鼠(Myf5-Cre;以Slo1flox/flox小鼠(CKO)为体内模型，研究Slo1在肌肉生长和肌肉再生中的作用。采用前肢握力试验评估骨骼肌功能，采用跑步机疲劳试验评估全身耐力。小鼠原代成肌细胞来源于CKO(成肌细胞/CKO)小鼠，将研究结果扩展到体外对成肌细胞分化和融合的影响。采用实时荧光定量PCR、western blot和免疫荧光法分析Slo1在成肌细胞分化和肌肉再生过程中的表达。为了研究基因在Slo1缺失诱导的肌肉功能障碍调控中的作用，我们对原代成肌细胞进行了RNA-seq分析。免疫沉淀法和质谱法鉴定了与Slo1相互作用的蛋白。双荧光素酶报告试验用于鉴定Slo1缺失是否影响NFAT活性。结果CKO小鼠的体重和体型与Slo1flox/flox小鼠(称为WT)没有显著差异。肌肉中Slo1的缺乏导致耐力降低(~30%，P <0.05)和强度(降低~30%，P <0.001)。虽然肌肉的一般形态没有差异，但电镜显示比目鱼肌线粒体含量明显减少(约减少40%，P <0.01)。我们发现Slo1主要在细胞膜上表达，在慢肌纤维中表达较多。Slo1蛋白的表达在肌肉产后发育和损伤后再生过程中逐渐降低，在成肌细胞分化过程中表达强烈降低。Slo1缺失损害成肌细胞分化和慢肌纤维形成。在机制上，RNA-seq分析显示Slo1影响与肌分化和慢肌纤维形成相关的基因表达。Slo1与FAK相互作用影响肌源性分化，Slo1缺失会降低NFAT活性。结论:我们的数据显示，Slo1缺乏会损害骨骼肌再生和慢肌纤维的形成。
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引用次数: 0
Biomarkers and mechanisms associated with cancer-induced cardiac cachexia: A systematic review 与癌症诱导的心脏恶病质相关的生物标志物和机制:系统综述
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-21 DOI: 10.1002/jcsm.13267
Lisa Bagnall, Oliver Grundmann, Marilyn G. Teolis, Saun-Joo L. Yoon

Cancer cachexia is a severe multifactorial syndrome1 that affects up to 80% of patients with advanced cancer, causing death in 20–80% with no effective treatments.2, 3 It causes multi-organ alteration and loss of skeletal and cardiac (myocardium) muscle mass.4, 5 Cardiac muscle wasting may result from cardiac protein loss associated with increased oxygen consumption and energy expenditure, resulting in cardiac insufficiency.5 It is hypothesized that significant tissue inflammation and oxidative stress during cancer progression cause cardiac wasting-associated cardiomyopathy, such as a thinned ventricular wall, local tissue hypoxia and arrhythmias.6 This review provided available evidence of cancer-induced cardiac cachexia in human and non-human models by examining biomarkers and the contributing factors to the development and progression of cardiac cachexia. Investigation of the potential biomarkers affecting cardiac muscle wasting is essential for improving patient outcomes.

Our knowledge about the causes of cardiac cachexia in cancer remains limited and the possible mechanisms have only been explored in animal studies to date. A better understanding of the pathophysiology of cardiac cachexia may help to determine if targeted therapies can effectively block the upregulation of various genes and cytokines that initiate and facilitate cancer-induced cardiac cachexia. Understanding the distinct nature of cancer-related cardiac cachexia and what distinguishes it from other causes may also lead to finding targeted, effective treatments. Treating cardiac cachexia early and before clinical changes are noted may improve overall cardiac function and lead to better patient outcomes.

The authors have no conflicts of interest.

癌症恶病质是一种严重的多因子综合征，影响多达80%的晚期癌症患者，在没有有效治疗的情况下导致20-80%的患者死亡。它引起多器官的改变和骨骼和心脏(心肌)肌肉质量的损失。4,5心肌萎缩可能是由于心肌蛋白损失与氧气消耗和能量消耗增加有关，从而导致心脏功能不全据推测，癌症进展过程中显著的组织炎症和氧化应激导致心脏消耗相关的心肌病，如心室壁变薄、局部组织缺氧和心律失常本综述通过检测心脏恶病质的生物标志物和影响因素，在人类和非人类模型中提供了癌症诱导的心脏恶病质的现有证据。研究影响心肌萎缩的潜在生物标志物对于改善患者预后至关重要。我们对癌症中心脏恶病质原因的了解仍然有限，迄今为止仅在动物研究中探索了可能的机制。更好地了解心脏恶病质的病理生理可能有助于确定靶向治疗是否可以有效阻断启动和促进癌症诱导的心脏恶病质的各种基因和细胞因子的上调。了解与癌症相关的心脏恶病质的独特性质，以及它与其他原因的区别，也可能有助于找到有针对性的、有效的治疗方法。早期治疗心脏恶病质和在临床变化之前可能会改善整体心功能并导致更好的患者预后。作者没有利益冲突。
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引用次数: 0
Association of muscle wasting with mortality risk among adults: A systematic review and meta-analysis of prospective studies 成人肌肉萎缩与死亡风险的关系:前瞻性研究的系统回顾和荟萃分析
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-20 DOI: 10.1002/jcsm.13263
Huan-Huan Zhou, Yuxiao Liao, Zhao Peng, Fang Liu, Qi Wang, Wei Yang

The relationship between muscle wasting and mortality risk in the general population remains unclear. Our study was conducted to examine and quantify the associations between muscle wasting and all-cause and cause-specific mortality risks. PubMed, Web of Science and Cochrane Library were searched until 22 March 2023 for main data sources and references of retrieved relevant articles. Prospective studies investigating the associations of muscle wasting with risks of all-cause and cause-specific mortality in the general population were eligible. A random-effect model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the lowest versus normal categories of muscle mass. Subgroup analyses and meta-regression were performed to investigate the potential sources of heterogeneities among studies. Dose–response analyses were conducted to evaluate the relationship between muscle mass and mortality risk. Forty-nine prospective studies were included in the meta-analysis. A total of 61 055 deaths were ascertained among 878 349 participants during the 2.5- to 32-year follow-up. Muscle wasting was associated with higher mortality risks of all causes (RR = 1.36, 95% CI, 1.28 to 1.44, I2 = 94.9%, 49 studies), cardiovascular disease (CVD) (RR = 1.29, 95% CI, 1.05 to 1.58, I2 = 88.1%, 8 studies), cancer (RR = 1.14, 95% CI, 1.02 to 1.27, I2 = 38.7%, 3 studies) and respiratory disease (RR = 1.36, 95% CI, 1.11 to 1.67, I2 = 62.8%, 3 studies). Subgroup analyses revealed that muscle wasting, regardless of muscle strength, was significantly associated with a higher all-cause mortality risk. Meta-regression showed that risks of muscle wasting-related all-cause mortality (P = 0.06) and CVD mortality (P = 0.09) were lower in studies with longer follow-ups. An approximately inverse linear dose–response relationship was observed between mid-arm muscle circumference and all-cause mortality risk (P < 0.01 for non-linearity). Muscle wasting was associated with higher mortality risks of all causes, CVD, cancer and respiratory disease in the general population. Early detection and treatment for muscle wasting might be crucial for reducing mortality risk and promoting healthy longevity.

在一般人群中，肌肉萎缩与死亡风险之间的关系尚不清楚。我们的研究是为了检查和量化肌肉萎缩与全因和特定原因死亡率风险之间的关系。检索PubMed、Web of Science和Cochrane Library，检索到2023年3月22日检索到的相关文章的主要数据源和参考文献。在普通人群中调查肌肉萎缩与全因和特定原因死亡率风险之间关系的前瞻性研究是合格的。采用随机效应模型计算最低肌肉质量与正常肌肉质量类别的合并相对危险度(RR)和95%置信区间(ci)。进行亚组分析和meta回归来调查研究间异质性的潜在来源。进行剂量-反应分析以评估肌肉量与死亡风险之间的关系。49项前瞻性研究被纳入meta分析。在2.5年至32年的随访期间，878349名参与者共确定了61055例死亡。肌肉萎缩与所有原因较高的死亡风险相关(RR = 1.36, 95% CI, 1.28至1.44,I2 = 94.9%， 49项研究)、心血管疾病(RR = 1.29, 95% CI, 1.05至1.58,I2 = 88.1%， 8项研究)、癌症(RR = 1.14, 95% CI, 1.02至1.27,I2 = 38.7%， 3项研究)和呼吸系统疾病(RR = 1.36, 95% CI, 1.11至1.67,I2 = 62.8%， 3项研究)。亚组分析显示，与肌肉力量无关的肌肉萎缩与较高的全因死亡风险显著相关。meta回归显示，在随访时间较长的研究中，肌肉萎缩相关的全因死亡率(P = 0.06)和心血管疾病死亡率(P = 0.09)的风险较低。中臂肌肉围度与全因死亡风险呈近似反比的线性剂量-反应关系(P <0.01表示非线性)。在一般人群中，肌肉萎缩与各种原因、心血管疾病、癌症和呼吸系统疾病的较高死亡风险有关。肌肉萎缩的早期发现和治疗可能对降低死亡风险和促进健康长寿至关重要。
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引用次数: 2
Androgen receptor coordinates muscle metabolic and contractile functions 雄激素受体协调肌肉代谢和收缩功能
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-20 DOI: 10.1002/jcsm.13251
Kamar Ghaibour, Mélanie Schuh, Sirine Souali-Crespo, Céline Chambon, Anouk Charlot, Joe Rizk, Daniela Rovito, Anna-Isavella Rerra, Qingshuang Cai, Nadia Messaddeq, Joffrey Zoll, Delphine Duteil, Daniel Metzger

Background

Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb muscles impairs sarcomere myofibrillar organization and decreases muscle strength in male mice. However, despite numerous studies performed in men and rodents, the signalling pathways controlled by androgens via their receptor in skeletal muscles remain poorly understood.

Methods

Male ARskm−/y (n = 7–12) and female ARskm−/− mice (n = 9), in which AR is selectively ablated in myofibres of musculoskeletal tissue, and male AR(i)skm−/y, in which AR is selectively ablated in post-mitotic skeletal muscle myofibres (n = 6), were generated. Longitudinal monitoring of body weight, blood glucose, insulin, lipids and lipoproteins was performed, alongside metabolomic analyses. Glucose metabolism was evaluated in C2C12 cells treated with 5α-dihydrotestosterone (DHT) and the anti-androgen flutamide (n = 6). Histological analyses on macroscopic and ultrastructural levels of longitudinal and transversal muscle sections were conducted. The transcriptome of gastrocnemius muscles from control and ARskm−/y mice was analysed at the age of 9 weeks (P < 0.05, 2138 differentially expressed genes) and validated by RT-qPCR analysis. The AR (4691 peaks with false discovery rate [FDR] < 0.1) and H3K4me2 (47 225 peaks with FDR < 0.05) cistromes in limb muscles were determined in 11-week-old wild-type mice.

Results

We show that disrupting the androgen/AR axis impairs in vivo glycolytic activity and fastens the development of type 2 diabetes in male, but not in female mice. In agreement, treatment with DHT increases glycolysis in C2C12 myotubes by 30%, whereas flutamide has an opposite effect. Fatty acids are less efficiently metabolized in skeletal muscles of ARskm−/y mice and accumulate in cytoplasm, despite increased transcript levels of genes encoding key enzymes of beta-oxidation and mitochondrial content. Impaired glucose and fatty acid metabolism in AR-deficient muscle fibres is associated with 30% increased lysine and branched-chain amino acid catabolism, decreased polyamine biosynthesis and disrupted glutamate transamination. This metabolic switch generates ammonia (2-fold increase) and oxidative stress (30% increased H2O2 levels), which impacts mitochondrial functions and causes necrosis in <1% fibres. We unravel that AR directly activates the transcription of genes invo

雄激素是一种合成代谢类固醇激素，通过与雄激素受体(AR)结合来发挥其功能。我们之前已经证实，雄性小鼠肢体肌肉的AR缺乏会损害肌节肌纤维组织并降低肌肉力量。然而，尽管在男性和啮齿动物中进行了大量的研究，雄激素通过骨骼肌受体控制的信号通路仍然知之甚少。方法制备雄性ARskm - /y (n = 7-12)和雌性ARskm - / -小鼠(n = 9)，其中AR在肌肉骨骼组织肌纤维中被选择性消融，雄性AR(i)skm - /y在有丝分裂后骨骼肌肌纤维中被选择性消融(n = 6)。进行了体重、血糖、胰岛素、血脂和脂蛋白的纵向监测，并进行了代谢组学分析。用5α-二氢睾酮(DHT)和抗雄激素氟他胺(n = 6)处理C2C12细胞，观察其糖代谢情况，并对纵、横肌切片进行宏观和超微结构水平的组织学分析。对照小鼠和ARskm - /y小鼠在9周龄时进行腓肠肌转录组分析(P <0.05, 2138个差异表达基因)，并通过RT-qPCR分析验证。AR(4691)峰值具有错误发现率[FDR] <0.1)和H3K4me2(47 225峰与FDR <0.05)测定11周龄野生型小鼠肢体肌肉的囊泡。我们发现，破坏雄激素/AR轴会损害雄性小鼠体内糖酵解活性，并加速2型糖尿病的发展，而雌性小鼠则不会。与此一致的是，DHT治疗可使C2C12肌管中的糖酵解增加30%，而氟他胺则有相反的效果。尽管编码β -氧化关键酶和线粒体含量的基因转录水平增加，但脂肪酸在ARskm - /y小鼠骨骼肌中的代谢效率较低，并在细胞质中积累。ar缺陷肌纤维中葡萄糖和脂肪酸代谢受损与赖氨酸和支链氨基酸分解代谢增加30%、多胺生物合成减少和谷氨酸转氨化中断有关。这种代谢开关会产生氨(增加2倍)和氧化应激(H2O2水平增加30%)，从而影响线粒体功能并导致1%的纤维坏死。我们揭示了AR直接激活参与糖酵解、氧化代谢和肌肉收缩的基因的转录。结论我们的研究为肌肉骨骼系统AR功能受损引起的疾病提供了重要的见解，并提供了对骨骼肌病理生理动力学的更深入了解，有助于开发有效的肌肉疾病治疗方法。
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引用次数: 6
SPSB1-mediated inhibition of TGF-β receptor-II impairs myogenesis in inflammation spsb1介导的TGF-β受体ii抑制可损害炎症中的肌生成
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-20 DOI: 10.1002/jcsm.13252
Yi Li, Niklas D?rmann, Bj?rn Brinschwitz, Melanie Kny, Elisa Martin, Kirsten Bartels, Ning Li, Priyanka Voori Giri, Stefan Schwanz, Michael Boschmann, Susanne Hille, Britta Fielitz, Tobias Wollersheim, Julius Grunow, Stephan B. Felix, Steffen Weber-Carstens, Friedrich C. Luft, Oliver J. Müller, Jens Fielitz

Background

Sepsis-induced intensive care unit-acquired weakness (ICUAW) features profound muscle atrophy and attenuated muscle regeneration related to malfunctioning satellite cells. Transforming growth factor beta (TGF-β) is involved in both processes. We uncovered an increased expression of the TGF-β receptor II (TβRII)-inhibitor SPRY domain-containing and SOCS-box protein 1 (SPSB1) in skeletal muscle of septic mice. We hypothesized that SPSB1-mediated inhibition of TβRII signalling impairs myogenic differentiation in response to inflammation.

Methods

We performed gene expression analyses in skeletal muscle of cecal ligation and puncture- (CLP) and sham-operated mice, as well as vastus lateralis of critically ill and control patients. Pro-inflammatory cytokines and specific pathway inhibitors were used to quantitate Spsb1 expression in myocytes. Retroviral expression plasmids were used to investigate the effects of SPSB1 on TGF-β/TβRII signalling and myogenesis in primary and immortalized myoblasts and differentiated myotubes. For mechanistical analyses we used coimmunoprecipitation, ubiquitination, protein half-life, and protein synthesis assays. Differentiation and fusion indices were determined by immunocytochemistry, and differentiation factors were quantified by qRT-PCR and Western blot analyses.

Results

SPSB1 expression was increased in skeletal muscle of ICUAW patients and septic mice. Tumour necrosis factor (TNF), interleukin-1β (IL-1β), and IL-6 increased the Spsb1 expression in C2C12 myotubes. TNF- and IL-1β-induced Spsb1 expression was mediated by NF-κB, whereas IL-6 increased the Spsb1 expression via the glycoprotein 130/JAK2/STAT3 pathway. All cytokines reduced myogenic differentiation. SPSB1 avidly interacted with TβRII, resulting in TβRII ubiquitination and destabilization. SPSB1 impaired TβRII-Akt-Myogenin signalling and diminished protein synthesis in myocytes. Overexpression of SPSB1 decreased the expression of early (Myog, Mymk, Mymx) and late (Myh1, 3, 7) differentiation-markers. As a result, myoblast fusion and myogenic differentiation were impaired. These effects were mediated by the SPRY- and SOCS-box domains of SPSB1. Co-expression of SPSB1 with Akt or Myogenin reversed the inhibitory effects of SPSB1 on protein synthesis and myogenic differentiation. Downregulation of Spsb1 by AAV9-mediated shRNA attenuated muscle weight loss and atrophy gene expression in skeletal muscle of septic mice.

背景败血症引起的重症监护病房获得性虚弱(ICUAW)的特征是与卫星细胞功能障碍相关的严重肌肉萎缩和肌肉再生减弱。转化生长因子β (TGF-β)参与了这两个过程。我们发现在脓毒症小鼠骨骼肌中TGF-β受体II (TβRII)抑制剂SPRY结构域和SOCS-box蛋白1 (SPSB1)的表达增加。我们假设spsb1介导的TβRII信号抑制会损害炎症反应中的肌源性分化。方法对盲肠结扎穿刺(CLP)和假手术小鼠骨骼肌以及危重患者和对照患者的股外侧肌进行基因表达分析。使用促炎细胞因子和特异性途径抑制剂定量测定Spsb1在肌细胞中的表达。利用逆转录病毒表达质粒研究SPSB1对原代、永生化肌母细胞和分化肌管中TGF-β/ t -β rii信号传导和肌发生的影响。对于机械分析，我们使用了共免疫沉淀，泛素化，蛋白质半衰期和蛋白质合成分析。免疫细胞化学检测分化融合指标，qRT-PCR和Western blot检测分化因子。结果SPSB1在ICUAW患者和脓毒症小鼠骨骼肌中表达升高。肿瘤坏死因子(TNF)、白细胞介素-1β (IL-1β)和IL-6增加了Spsb1在C2C12肌管中的表达。TNF-和il -1β-诱导的Spsb1表达由NF-κ b介导，而IL-6通过糖蛋白130/JAK2/STAT3通路增加Spsb1表达。所有细胞因子都减少了肌源性分化。SPSB1与TβRII相互作用，导致TβRII泛素化和不稳定。SPSB1损伤t- β rii - akt - myogenin信号传导和肌细胞蛋白合成。SPSB1过表达可降低早期(Myog、Mymk、Mymx)和晚期(Myh1、3,7)分化标志物的表达。结果，成肌细胞融合和成肌分化受到损害。这些作用是由SPSB1的SPRY-和SOCS-box结构域介导的。SPSB1与Akt或Myogenin共表达逆转了SPSB1对蛋白质合成和成肌分化的抑制作用。aav9介导的shRNA下调Spsb1可减轻脓毒症小鼠骨骼肌中肌肉失重和萎缩基因的表达。结论炎性细胞因子通过各自的信号通路导致SPSB1在肌细胞中的表达增加，并减弱成肌分化。spsb1介导的TβRII-Akt-Myogenin信号传导和蛋白质合成的抑制有助于炎症期间发生的肌细胞稳态紊乱和肌源性分化。
{"title":"SPSB1-mediated inhibition of TGF-β receptor-II impairs myogenesis in inflammation","authors":"Yi Li,&nbsp;Niklas D?rmann,&nbsp;Bj?rn Brinschwitz,&nbsp;Melanie Kny,&nbsp;Elisa Martin,&nbsp;Kirsten Bartels,&nbsp;Ning Li,&nbsp;Priyanka Voori Giri,&nbsp;Stefan Schwanz,&nbsp;Michael Boschmann,&nbsp;Susanne Hille,&nbsp;Britta Fielitz,&nbsp;Tobias Wollersheim,&nbsp;Julius Grunow,&nbsp;Stephan B. Felix,&nbsp;Steffen Weber-Carstens,&nbsp;Friedrich C. Luft,&nbsp;Oliver J. Müller,&nbsp;Jens Fielitz","doi":"10.1002/jcsm.13252","DOIUrl":"https://doi.org/10.1002/jcsm.13252","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis-induced intensive care unit-acquired weakness (ICUAW) features profound muscle atrophy and attenuated muscle regeneration related to malfunctioning satellite cells. Transforming growth factor beta (TGF-β) is involved in both processes. We uncovered an increased expression of the TGF-β receptor II (TβRII)-inhibitor SPRY domain-containing and SOCS-box protein 1 (SPSB1) in skeletal muscle of septic mice. We hypothesized that SPSB1-mediated inhibition of TβRII signalling impairs myogenic differentiation in response to inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed gene expression analyses in skeletal muscle of cecal ligation and puncture- (CLP) and sham-operated mice, as well as <i>vastus lateralis</i> of critically ill and control patients. Pro-inflammatory cytokines and specific pathway inhibitors were used to quantitate <i>Spsb1</i> expression in myocytes. Retroviral expression plasmids were used to investigate the effects of SPSB1 on TGF-β/TβRII signalling and myogenesis in primary and immortalized myoblasts and differentiated myotubes. For mechanistical analyses we used coimmunoprecipitation, ubiquitination, protein half-life, and protein synthesis assays. Differentiation and fusion indices were determined by immunocytochemistry, and differentiation factors were quantified by qRT-PCR and Western blot analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>SPSB1</i> expression was increased in skeletal muscle of ICUAW patients and septic mice. Tumour necrosis factor (TNF), interleukin-1β (IL-1β), and IL-6 increased the <i>Spsb1</i> expression in C2C12 myotubes. TNF- and IL-1β-induced <i>Spsb1</i> expression was mediated by NF-κB, whereas IL-6 increased the <i>Spsb1</i> expression via the glycoprotein 130/JAK2/STAT3 pathway. All cytokines reduced myogenic differentiation. SPSB1 avidly interacted with TβRII, resulting in TβRII ubiquitination and destabilization. SPSB1 impaired TβRII-Akt-Myogenin signalling and diminished protein synthesis in myocytes. Overexpression of SPSB1 decreased the expression of early (<i>Myog</i>, <i>Mymk</i>, <i>Mymx</i>) and late (<i>Myh1</i>, <i>3</i>, <i>7</i>) differentiation-markers. As a result, myoblast fusion and myogenic differentiation were impaired. These effects were mediated by the SPRY- and SOCS-box domains of SPSB1. Co-expression of SPSB1 with Akt or Myogenin reversed the inhibitory effects of SPSB1 on protein synthesis and myogenic differentiation. Downregulation of <i>Spsb1</i> by AAV9-mediated shRNA attenuated muscle weight loss and atrophy gene expression in skeletal muscle of septic mice.</p>\u0000 </section>\u0000 ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1721-1736"},"PeriodicalIF":8.9,"publicationDate":"2023-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5779221","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}
引用次数: 0
Muscle size and density are independently associated with death after hip fracture: A prospective cohort study 肌肉大小和密度与髋部骨折后死亡独立相关:一项前瞻性队列研究
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-05-19 DOI: 10.1002/jcsm.13261
Ling Wang, Minghui Yang, Yufeng Ge, Yandong Liu, Yongbin Su, Zhe Guo, Pengju Huang, Jian Geng, Gang Wang, Glen M. Blake, Bo He, Lu Yin, Xiaoguang Cheng, Xinbao Wu, Klaus Engelke, Annegreet G. Vlug

Background

Mortality following hip fracture is high and incompletely understood. We hypothesize that hip musculature size and quality are related to mortality following hip fracture. This study aims to investigate the associations of hip muscle area and density from hip CT with death following hip fracture as well as assess the dependence of this association on time after hip fracture.

Methods

In this secondary analysis of the prospectively collected CT images and data from the Chinese Second Hip Fracture Evaluation, 459 patients were enrolled between May 2015 and June 2016 and followed up for a median of 4.5 years. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur. The Goutallier classification (GC) was used for qualitatively assessing muscle fat infiltration. Separate Cox models were used to predict mortality risk adjusted for covariates.

Results

At the end of the follow-up, 85 patients were lost, 81 patients (64% women) had died, and 293 (71% women) survived. The mean age of non-surviving patients at death (82.0 ± 8.1 years) was higher than that of the surviving patients (74.4 ± 9.9 years). The Parker Mobility Score and the American Society of Anesthesiologists scores of the patients that died were respectively lower and higher compared to the surviving patients. Hip fracture patients received different surgical procedures, and no significant difference in the percentage of hip arthroplasty was observed between the dead and the surviving patients (P = 0.11). The cumulative survival was significantly lower for patients with low G.MaxM area and density and low G.Med/MinM density, independent of age and clinical risk scores. The GC grades were not associated with the mortality after hip fracture. Muscle density of both G.MaxM (adj. HR 1.83; 95% CI, 1.06–3.17) and G.Med/MinM (adj. HR 1.98; 95% CI, 1.14–3.46) was associated with mortality in the 1st year after hip fracture. G.MaxM area (adj. HR 2.11; 95% CI, 1.08–4.14) was associated with mortality in the 2nd and later years after hip fracture.

Conclusion

Our results for the first time show that hip muscle size and density are associated with mortality in older hip fracture patients, independent of age and clinical risk scores. This is an important finding to better understand the factors contributing to the high mortality in older hip fracture

背景:髋部骨折后的死亡率很高，目前还不完全清楚。我们假设髋部肌肉组织的大小和质量与髋部骨折后的死亡率有关。本研究旨在探讨髋部CT显示的髋部肌肉面积和密度与髋部骨折后死亡的关系，并评估这种关系与髋部骨折后时间的依赖关系。方法对2015年5月至2016年6月期间前瞻性收集的中国第二次髋部骨折评估的CT图像和数据进行二次分析，纳入459例患者，中位随访时间为4.5年。测量股骨近端臀大肌(G.MaxM)、臀中、小肌(G.Med/MinM)和aBMD的肌肉横截面积和密度。采用Goutallier分级法(GC)定性评价肌肉脂肪浸润。使用单独的Cox模型预测经协变量调整后的死亡风险。结果随访结束时，丢失85例，死亡81例(女性占64%)，存活293例(女性占71%)。非存活患者死亡时平均年龄(82.0±8.1岁)高于存活患者(74.4±9.9岁)。与存活患者相比，死亡患者的派克活动能力评分和美国麻醉医师协会评分分别较低和较高。髋部骨折患者接受不同的手术方式，死亡和存活患者的髋关节置换术百分比无显著差异(P = 0.11)。与年龄和临床风险评分无关，低g.m max面积和密度以及低g.m med /MinM密度的患者累积生存期显著降低。GC分级与髋部骨折后的死亡率无关。G.MaxM的肌肉密度(adj. HR 1.83;95% CI, 1.06-3.17)和g.m d/MinM (adj. HR 1.98;95% CI, 1.14-3.46)与髋部骨折后1年的死亡率相关。g .最大面积(adj. HR 2.11;95% CI, 1.08-4.14)与髋部骨折后2年及以后的死亡率相关。结论我们的研究结果首次表明，老年髋部骨折患者的髋部肌肉大小和密度与死亡率相关，与年龄和临床风险评分无关。这是一个重要的发现，可以更好地了解导致老年髋部骨折患者高死亡率的因素，并开发包括肌肉参数在内的更好的未来风险预测评分。
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