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Improved health by combining dietary restriction and promoting muscle growth in DNA repair-deficient progeroid mice. 通过限制饮食和促进 DNA 修复缺陷型早衰小鼠的肌肉生长,改善其健康状况。
IF 8.9 1区 医学 Pub Date : 2024-09-08 DOI: 10.1002/jcsm.13570
Wilbert P Vermeij, Khalid Alyodawi, Ivar van Galen, Jennie L von der Heide, María B Birkisdóttir, Lisanne J Van't Sant, Rutger A Ozinga, Daphne S J Komninos, Kimberly Smit, Yvonne M A Rijksen, Renata M C Brandt, Sander Barnhoorn, Dick Jaarsma, Sathivel Vaiyapuri, Olli Ritvos, Tobias B Huber, Oliver Kretz, Ketan Patel

Background: Ageing is a complex multifactorial process, impacting all organs and tissues, with DNA damage accumulation serving as a common underlying cause. To decelerate ageing, various strategies have been applied to model organisms and evaluated for health and lifespan benefits. Dietary restriction (DR, also known as caloric restriction) is a well-established long-term intervention recognized for its universal anti-ageing effects. DR temporarily suppresses growth, and when applied to progeroid DNA repair-deficient mice doubles lifespan with systemic health benefits. Counterintuitively, attenuation of myostatin/activin signalling by soluble activin receptor (sActRIIB), boosts the growth of muscle and, in these animals, prevents muscle wasting, improves kidney functioning, and compresses morbidity.

Methods: Here, we investigated a combined approach, applying an anabolic regime (sActRIIB) at the same time as DR to Ercc1Δ/- progeroid mice. Following both single treatments and combined, we monitored global effects on body weight, lifespan and behaviour, and local effects on muscle and tissue weight, muscle morphology and function, and ultrastructural and transcriptomic changes in muscle and kidney.

Results: Lifespan was mostly influenced by DR (extended from approximately 20 to 40 weeks; P < 0.001), with sActRIIB clearly increasing muscle mass (35-65%) and tetanic force (P < 0.001). The combined regime yielded a stable uniform body weight, but increased compared with DR alone, synergistically improved motor coordination and further delayed the onset and development of balance problems. sActRIIB significantly increased muscle fibre size (P < 0.05) in mice subjected to DR and lowered all signs of muscle damage. Ercc1Δ/- mice showed abnormal neuromuscular junctions. Single interventions by sActRIIB treatment or DR only partially rescued this phenotype, while in the double intervention group, the regularly shaped junctional foldings were maintained. In kidney of Ercc1Δ/- mice, we observed a mild but significant foot process effacement, which was restored by either intervention. Transcriptome analysis also pointed towards reduced levels of DNA damage in muscle and kidney by DR, but not sActRIIB, while these levels retained lower in the double intervention.

Conclusions: In muscle, we found synergistic effects of combining sActRIIB with DR, but not in kidney, with an overall better health in the double intervention group. Crucially, the benefits of each single intervention are not lost when administered in combination, but rather strengthened, even when sActRIIB was applied late in life, opening opportunities for translation to human.

背景:衰老是一个复杂的多因素过程,影响到所有器官和组织,而 DNA 损伤积累是一个共同的根本原因。为了延缓衰老,人们在模式生物中应用了各种策略,并评估了这些策略对健康和寿命的益处。饮食限制(DR,又称热量限制)是一种行之有效的长期干预措施,因其普遍的抗衰老效果而得到认可。DR 可暂时抑制生长,应用于早衰 DNA 修复缺陷小鼠时,可使寿命延长一倍,并对全身健康有益。与直觉相反,可溶性激活素受体(sActRIIB)可抑制肌生长蛋白/激活素信号,促进肌肉生长,并在这些动物中防止肌肉萎缩、改善肾功能和降低发病率。方法:在此,我们研究了一种综合方法,即在对 Ercc1Δ/- 类早衰小鼠进行 DR 治疗的同时应用合成代谢机制(sActRIIB)。在单一治疗和联合治疗后,我们监测了对体重、寿命和行为的整体影响,以及对肌肉和组织重量、肌肉形态和功能、肌肉和肾脏超微结构和转录组变化的局部影响:寿命主要受DR的影响(从大约20周延长到40周;P Δ/-小鼠表现出异常的神经肌肉接头。sActRIIB 处理或 DR 的单次干预只能部分缓解这种表型,而在双重干预组中,规则形状的连接皱褶得以保持。在 Ercc1Δ/- 小鼠的肾脏中,我们观察到了轻微但显著的足突脱出现象,无论采用哪种干预方法,这种现象都能得到恢复。转录组分析还表明,DR降低了肌肉和肾脏中的DNA损伤水平,但sActRIIB没有降低,而这些水平在双重干预中保持较低水平:在肌肉中,我们发现了 sActRIIB 与 DR 的协同作用,但在肾脏中却没有发现,双重干预组的总体健康状况更好。最重要的是,每种单一干预措施的益处在联合应用时不仅没有丧失,反而得到了加强,即使是在生命晚期应用 sActRIIB 也是如此,这为向人类转化提供了机会。
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引用次数: 0
Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men. 鞘脂代谢物是男性肌肉疏松症的潜在循环生物标志物。
IF 8.9 1区 医学 Pub Date : 2024-09-04 DOI: 10.1002/jcsm.13582
Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young-Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee

Background: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics.

Methods: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort.

Results: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799).

Conclusions: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.

背景:肌肉疏松症是一种与年龄有关的肌肉质量和功能逐渐丧失的疾病。肌肉疏松症是一种多因素疾病,包括代谢紊乱;因此,代谢物可作为肌肉疏松症的循环生物标志物。我们旨在利用代谢组学研究潜在的肌肉疏松症生物标志物:在对衰老型肌肉疏松症小鼠模型的血浆进行非靶向代谢组学分析后,使用靶向代谢组学分析对该动物模型的鞘脂代谢物和肌肉细胞进行了评估。在年龄匹配的发现队列(72 个病例和 72 个对照组)和验证队列(36 个病例和 128 个对照组)中,评估了从小鼠和细胞研究中发现的鞘脂代谢物与肌肉疏松症状态之间的关联;患有肌肉疏松症的女性(36 个病例和 36 个对照组)也被纳入发现队列:结果:实验研究中的非靶向和靶向代谢组分析表明,鞘脂代谢物(包括神经酰胺(CERs)和鞘磷脂(SMs))与肌肉疏松症之间存在关联。发现队列中患有肌肉疏松症的男性血浆 SM(16:0)、CER(24:1)和 SM(24:1)水平明显高于对照组(均为 P 结论):SM(16:0)反映肌肉强度低,CER(24:1)和SM(16:0)反映肌肉质量低,是男性肌肉疏松症的潜在循环生物标志物。我们需要进一步研究鞘脂代谢物,以证实这些结果,并进一步了解与肌肉疏松症的发病机制和诊断有关的代谢组变化。
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引用次数: 0
Leptin signalling altered in infantile nephropathic cystinosis‐related bone disorder 瘦素信号在婴幼儿肾病性胱氨酸病相关骨病中发生改变
IF 8.9 1区 医学 Pub Date : 2024-08-30 DOI: 10.1002/jcsm.13579
Wai W. Cheung, Ping Zhou, Ronghao Zheng, Arieh Gertler, Eduardo A. Oliveira, Robert H. Mak
BackgroundThe <jats:italic>CTNS</jats:italic> gene mutation causes infantile nephropathic cystinosis (INC). Patients with INC develop Fanconi syndrome and chronic kidney disease (CKD) with significant bone deformations. C57BL/6 <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice are an animal model for studying INC. Hyperleptinaemia results from the kidney's inability to eliminate the hormone leptin in CKD. <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice have elevated serum leptin concentrations. Leptin regulates bone metabolism through its receptor that signals further via the hypothalamic melanocortin 4 receptor (MC4R). Leptin signalling may affect bone health in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice.MethodsWe first defined the time course of bone abnormalities in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice between 1 and 12 months of age. We used both genetic and pharmacological approaches to investigate leptin signalling in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice. We generated <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup><jats:italic>Mc4r</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> double knockout mice. Bone phenotype of <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup><jats:italic>Mc4r</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice, <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice and wild type (WT) mice at 1, 4, and 9 months of age were compared. We then treated 12‐month‐old <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice and WT mice with a pegylated leptin receptor antagonist (PLA) (7 mg/kg/day, IP), a MC4R antagonist agouti‐related peptide (AgRP) (2 nmol, intracranial infusion on days 0, 3, 6, 9, 12, 15, 18, 21, 24, and 27), or vehicle (normal saline), respectively, for 28 days. Whole‐body (BMC/BMD, bone area) and femoral bone phenotype (BMC/BMD, bone area, length and failure load) of mice were measured by DXA and femoral shaft biochemical test. We also measured lean mass content by EchoMRI and muscle function (grip strength and rotarod activity) in mice. Femur protein content of JAK2 and STAT3 was measured by ELISA kits, respectively.ResultsBone defects are present in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice throughout its first year of life. The deletion of the <jats:italic>Mc4r</jats:italic> gene attenuated bone disorder in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice. Femoral BMD, bone area, length, and strength (failure load) were significantly increased in 9‐month‐old <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></ja
背景CTNS基因突变导致婴儿肾病性胱氨酸病(INC)。INC 患者会患上范可尼综合征(Fanconi syndrome)和慢性肾病(CKD),并伴有明显的骨骼变形。C57BL/6 Ctns-/- 小鼠是研究 INC 的动物模型。高瘦素血症是由于 CKD 中肾脏无法排出瘦素激素所致。Ctns-/- 小鼠的血清瘦素浓度升高。瘦素通过其受体调节骨代谢,该受体通过下丘脑黑色素皮质素 4 受体(MC4R)进一步发出信号。我们首先确定了 Ctns-/- 小鼠在 1 到 12 个月大时骨骼异常的时间过程。我们采用遗传和药理学方法研究了 Ctns-/- 小鼠体内的瘦素信号。我们产生了 Ctns-/-Mc4r-/- 双基因敲除小鼠。比较了 1、4 和 9 个月大的 Ctns-/-Mc4r-/- 小鼠、Ctns-/- 小鼠和野生型(WT)小鼠的骨骼表型。然后,我们用聚乙二醇化瘦素受体拮抗剂(PLA)(7 毫克/千克/天,IP)、MC4R 拮抗剂激动相关肽(AgRP)(2 毫摩尔,第 0、3、6、9、12、15、18、21、24 和 27 天颅内灌注)或载体(生理盐水)分别治疗 12 个月大的 Ctns-/- 小鼠和 WT 小鼠 28 天。小鼠全身(BMC/BMD、骨面积)和股骨表型(BMC/BMD、骨面积、骨长度和失效负荷)通过 DXA 和股骨干生化测试进行测量。我们还通过 EchoMRI 测量了小鼠的瘦肉含量和肌肉功能(握力和转体活动)。结果 Ctns-/-小鼠在出生后的第一年都存在骨骼缺陷。Ctns-/-小鼠在出生后的第一年内都存在骨缺陷,Mc4r基因的缺失减轻了Ctns-/-小鼠的骨紊乱。与年龄匹配的 Ctns-/- 小鼠相比,9 个月大的 Ctns-/-Mc4r-/- 小鼠的股骨 BMD、骨面积、骨长度和骨强度(破坏负荷)均显著增加。聚乳酸和AgRP处理可明显增加12月龄Ctns-/-小鼠的股骨密度(BMC/BMD)和机械强度。我们在这项研究中采用了配对喂养的方法,以证明 PLA 或 AgRP 对骨表型的保护作用独立于其强大的促矿物质效应。此外,Ctns-/小鼠瘦体重和体内肌肉功能(握力和转体活动)的增加与骨表型(股骨BMC/BMD和机械强度)的改善相关,这表明肌肉与骨骼之间存在相互作用。在 Ctns-/- 小鼠中,股骨 JAK2 和 STAT3 蛋白含量明显下降。结论:我们的研究结果表明,瘦素信号失调在 INC 相关骨质紊乱中起着重要作用,可能是直接作用,也可能涉及肌肉与骨骼之间的相互作用。阻断瘦素信号可能是治疗 INC 骨病和肌肉萎缩的一种新方法。
{"title":"Leptin signalling altered in infantile nephropathic cystinosis‐related bone disorder","authors":"Wai W. Cheung, Ping Zhou, Ronghao Zheng, Arieh Gertler, Eduardo A. Oliveira, Robert H. Mak","doi":"10.1002/jcsm.13579","DOIUrl":"https://doi.org/10.1002/jcsm.13579","url":null,"abstract":"BackgroundThe &lt;jats:italic&gt;CTNS&lt;/jats:italic&gt; gene mutation causes infantile nephropathic cystinosis (INC). Patients with INC develop Fanconi syndrome and chronic kidney disease (CKD) with significant bone deformations. C57BL/6 &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice are an animal model for studying INC. Hyperleptinaemia results from the kidney's inability to eliminate the hormone leptin in CKD. &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice have elevated serum leptin concentrations. Leptin regulates bone metabolism through its receptor that signals further via the hypothalamic melanocortin 4 receptor (MC4R). Leptin signalling may affect bone health in &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice.MethodsWe first defined the time course of bone abnormalities in &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice between 1 and 12 months of age. We used both genetic and pharmacological approaches to investigate leptin signalling in &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice. We generated &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt;&lt;jats:italic&gt;Mc4r&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; double knockout mice. Bone phenotype of &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt;&lt;jats:italic&gt;Mc4r&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice, &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice and wild type (WT) mice at 1, 4, and 9 months of age were compared. We then treated 12‐month‐old &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice and WT mice with a pegylated leptin receptor antagonist (PLA) (7 mg/kg/day, IP), a MC4R antagonist agouti‐related peptide (AgRP) (2 nmol, intracranial infusion on days 0, 3, 6, 9, 12, 15, 18, 21, 24, and 27), or vehicle (normal saline), respectively, for 28 days. Whole‐body (BMC/BMD, bone area) and femoral bone phenotype (BMC/BMD, bone area, length and failure load) of mice were measured by DXA and femoral shaft biochemical test. We also measured lean mass content by EchoMRI and muscle function (grip strength and rotarod activity) in mice. Femur protein content of JAK2 and STAT3 was measured by ELISA kits, respectively.ResultsBone defects are present in &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice throughout its first year of life. The deletion of the &lt;jats:italic&gt;Mc4r&lt;/jats:italic&gt; gene attenuated bone disorder in &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/jats:sup&gt; mice. Femoral BMD, bone area, length, and strength (failure load) were significantly increased in 9‐month‐old &lt;jats:italic&gt;Ctns&lt;/jats:italic&gt;&lt;jats:sup&gt;&lt;jats:italic&gt;−/−&lt;/jats:italic&gt;&lt;/ja","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Overall mortality for community‐dwelling adults over 50 years at risk of malnutrition 有营养不良风险的 50 岁以上居住在社区的成年人的总死亡率
IF 8.9 1区 医学 Pub Date : 2024-08-30 DOI: 10.1002/jcsm.13585
Matthew Gittins, Nada AlMohaisen, Chris Todd, Simon Lal, Sorrel Burden
BackgroundIt is well reported that malnutrition in acute care is associated with poorer health outcomes including increased mortality. However, the consequences of malnutrition on survival in community settings is uncertain. Malnutrition in people 65 years or over is often cited. Nevertheless, this study includes both middle‐aged and older adults as current public health policy is highlighting the need to increase disease‐free life years and is moving away from just extending life to increase overall longevity. The aim of this study is to describe the association of the risk of malnutrition using the Malnutrition Universal Screening Tool (MUST) with mortality in community‐dwelling middle‐aged and older adults.MethodsWe used the UK Biobank to investigate the association between those at risk of malnutrition and mortality in participants aged ≥50 years. MUST identified risk of malnutrition and linked data to national death registries confirmed mortality. Years of life lost (YLL) and Cox proportional hazard models with hazard ratios (HR) and confidence intervals (CI) described risk associated with all‐cause mortality.ResultsThere were 502 408 participants recruited, 117 830 were ≤50 years leaving 384 578 eligible participants. Based on MUST scores 63 495 (16.5%) were at risk of malnutrition with 401 missing some data and excluded. Incidence of mortality for at risk participants was 755 per 100 000 person‐years, corresponding to 153 476 YLL. Of those at risk of malnutrition, 9.5% died versus 7.8% at low risk. Initial survival analysis reported an increased risk of mortality (HR 1.29, 95% CI: 1.25 to 1.33) that decreased after adjusting for confounders (HR 1.14, 95% CI: 1.11 to 1.18) in those at risk of malnutrition versus those at low risk.ConclusionsRisk of malnutrition was associated with increased overall mortality. Modest effect sizes are demonstrated but are supportive of public health policies, which advocate wide‐scale community, based nutritional screening for middle‐aged and older adults.
背景据报道,急症护理中的营养不良与较差的健康状况(包括死亡率增加)有关。然而,营养不良对社区环境中生存的影响尚不确定。65岁或以上人群的营养不良问题经常被提及。不过,本研究既包括中年人,也包括老年人,因为当前的公共卫生政策正在强调提高无病生存年数的必要性,并从单纯延长寿命转向提高整体寿命。本研究的目的是利用营养不良通用筛查工具(MUST)描述社区中老年人营养不良风险与死亡率之间的关系。方法我们利用英国生物库调查了年龄≥50 岁的参与者中营养不良风险与死亡率之间的关系。MUST确定了营养不良的风险,并将数据链接到国家死亡登记处,确认了死亡率。损失寿命年数(YLL)和带有危险比(HR)和置信区间(CI)的 Cox 比例危险模型描述了与全因死亡率相关的风险。根据 MUST 评分,63 495 人(16.5%)有营养不良风险,其中 401 人因缺少某些数据而被排除在外。有营养不良风险的参与者的死亡率为每 10 万人年 755 例,相当于 153476 年的死亡率。在有营养不良风险的人群中,9.5%的人死亡,而低风险人群的死亡率为 7.8%。初步生存分析表明,营养不良风险者与低风险者相比,死亡风险增加(HR 1.29,95% CI:1.25 至 1.33),调整混杂因素后,死亡风险降低(HR 1.14,95% CI:1.11 至 1.18)。结论营养不良的风险与总死亡率的增加有关,其效应大小不大,但支持公共卫生政策,该政策提倡对中老年人进行大规模的社区营养筛查。
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引用次数: 0
Associations between gut microbiota and sarcopenia or its defining parameters in older adults: A systematic review. 老年人肠道微生物群与肌少症或其定义参数之间的关系:系统综述。
IF 8.9 1区 医学 Pub Date : 2024-08-27 DOI: 10.1002/jcsm.13569
Laurence Lapauw, Aurélie Rutten, Jolan Dupont, Nadjia Amini, Laura Vercauteren, Muriel Derrien, Jeroen Raes, Evelien Gielen

Altered gut microbiota (GM) potentially contribute to development or worsening of sarcopenia through a gut-muscle axis. This systematic review aims to compare GM between persons with sarcopenia or low sarcopenia-defining parameters (muscle mass, strength, and physical performance) to those with preserved muscle status, as well as to clarify possible associations between sarcopenia (-defining parameters) and relative abundance (RA) of GM-taxa or GM-(α- or β) diversity indices, in order to clarify whether there is robust evidence of the existence of a GM signature for sarcopenia. This systematic review was conducted according to the PRISMA-reporting guideline and pre-registered on PROSPERO (CRD42021259597). PubMed, Web of Science, Embase, ClinicalTrials.gov, and Cochrane library were searched until 20 July 2023. Included studies reported on GM and sarcopenia or its defining parameters. Observational studies were included with populations of mean age ≥50 years. Thirty-two studies totalling 10 781 persons (58.56% ♀) were included. Thirteen studies defined sarcopenia as a construct. Nineteen studies reported at least one sarcopenia-defining parameter (muscle mass, strength or physical performance). Studies found different GM-taxa at multiple levels to be significantly associated with sarcopenia (n = 4/6), muscle mass (n = 13/14), strength (n = 7/9), and physical performance (n = 3/3); however, directions of associations were heterogeneous and also conflicting for specific GM-taxa. Regarding β-diversity, studies found GM of persons with sarcopenia, low muscle mass, or low strength to cluster differently compared with persons with preserved muscle status. α-diversity was low in persons with sarcopenia or low muscle mass as compared with those with preserved muscle status, indicating low richness and diversity. In line with this, α-diversity was significantly and positively associated with muscle mass (n = 3/4) and muscle strength (n = 2/3). All reported results were significant (P < 0.05). Persons with sarcopenia and low muscle parameters have less rich and diverse GM and can be separated from persons with preserved muscle mass and function based on GM-composition. Sarcopenia and low muscle parameters are also associated with different GM-taxa at multiple levels, but results were heterogeneous and no causal conclusions could be made due to the cross-sectional design of the studies. This emphasizes the need for uniformly designed cross-sectional and longitudinal trials with appropriate GM confounder control in large samples of persons with sarcopenia and clearly defined core outcome sets in order to further explore changes in GM-taxa and to determine a sarcopenia-specific GM-signature.

肠道微生物群(GM)的改变可能会通过肠道-肌肉轴导致肌肉疏松症的发生或恶化。本系统综述旨在比较肌肉疏松症患者或肌肉疏松症定义参数(肌肉质量、力量和体能)较低者与肌肉状况保持良好者之间的肠道微生物群,并阐明肌肉疏松症(定义参数)与肠道微生物群-他或肠道微生物群-(α- 或 β)多样性指数的相对丰度(RA)之间可能存在的关联,以明确是否有可靠证据表明存在肌肉疏松症的肠道微生物群特征。本系统综述根据 PRISMA 报告指南进行,并在 PROSPERO 上进行了预先注册(CRD42021259597)。对 PubMed、Web of Science、Embase、ClinicalTrials.gov 和 Cochrane 图书馆进行了检索,直至 2023 年 7 月 20 日。纳入的研究报告了基因改造和肌少症或其定义参数。观察性研究的研究对象平均年龄≥50 岁。共纳入 32 项研究,共计 10 781 人(58.56%♀)。其中 13 项研究将 "肌肉疏松症 "定义为一种疾病。19项研究报告了至少一项界定 "肌肉疏松症 "的参数(肌肉质量、力量或体能)。研究发现,多层次的不同 GM-taxa与肌肉疏松症(4/6)、肌肉质量(13/14)、力量(7/9)和体能(3/3)有显著相关性;然而,对于特定的 GM-taxa,相关性的方向不尽相同,而且相互矛盾。关于 β 多样性,研究发现肌肉疏松症、肌肉质量低或力量低的人与肌肉状态保持良好的人相比,其基因组聚类不同。与肌肉状态保持良好的人相比,患有肌肉疏松症或肌肉质量低的人的α-多样性较低,这表明其丰富性和多样性较低。因此,α多样性与肌肉质量(n = 3/4)和肌肉力量(n = 2/3)呈显著正相关。所有报告结果均有显著性(P
{"title":"Associations between gut microbiota and sarcopenia or its defining parameters in older adults: A systematic review.","authors":"Laurence Lapauw, Aurélie Rutten, Jolan Dupont, Nadjia Amini, Laura Vercauteren, Muriel Derrien, Jeroen Raes, Evelien Gielen","doi":"10.1002/jcsm.13569","DOIUrl":"https://doi.org/10.1002/jcsm.13569","url":null,"abstract":"<p><p>Altered gut microbiota (GM) potentially contribute to development or worsening of sarcopenia through a gut-muscle axis. This systematic review aims to compare GM between persons with sarcopenia or low sarcopenia-defining parameters (muscle mass, strength, and physical performance) to those with preserved muscle status, as well as to clarify possible associations between sarcopenia (-defining parameters) and relative abundance (RA) of GM-taxa or GM-(α- or β) diversity indices, in order to clarify whether there is robust evidence of the existence of a GM signature for sarcopenia. This systematic review was conducted according to the PRISMA-reporting guideline and pre-registered on PROSPERO (CRD42021259597). PubMed, Web of Science, Embase, ClinicalTrials.gov, and Cochrane library were searched until 20 July 2023. Included studies reported on GM and sarcopenia or its defining parameters. Observational studies were included with populations of mean age ≥50 years. Thirty-two studies totalling 10 781 persons (58.56% ♀) were included. Thirteen studies defined sarcopenia as a construct. Nineteen studies reported at least one sarcopenia-defining parameter (muscle mass, strength or physical performance). Studies found different GM-taxa at multiple levels to be significantly associated with sarcopenia (n = 4/6), muscle mass (n = 13/14), strength (n = 7/9), and physical performance (n = 3/3); however, directions of associations were heterogeneous and also conflicting for specific GM-taxa. Regarding β-diversity, studies found GM of persons with sarcopenia, low muscle mass, or low strength to cluster differently compared with persons with preserved muscle status. α-diversity was low in persons with sarcopenia or low muscle mass as compared with those with preserved muscle status, indicating low richness and diversity. In line with this, α-diversity was significantly and positively associated with muscle mass (n = 3/4) and muscle strength (n = 2/3). All reported results were significant (P < 0.05). Persons with sarcopenia and low muscle parameters have less rich and diverse GM and can be separated from persons with preserved muscle mass and function based on GM-composition. Sarcopenia and low muscle parameters are also associated with different GM-taxa at multiple levels, but results were heterogeneous and no causal conclusions could be made due to the cross-sectional design of the studies. This emphasizes the need for uniformly designed cross-sectional and longitudinal trials with appropriate GM confounder control in large samples of persons with sarcopenia and clearly defined core outcome sets in order to further explore changes in GM-taxa and to determine a sarcopenia-specific GM-signature.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of cancer-associated cachexia in lung cancer patients using whole-body [18F]FDG-PET/CT imaging: A multi-centre study. 利用全身[18F]FDG-PET/CT成像检测肺癌患者的癌症相关恶病质:一项多中心研究。
IF 8.9 1区 医学 Pub Date : 2024-08-27 DOI: 10.1002/jcsm.13571
Daria Ferrara, Elisabetta M Abenavoli, Thomas Beyer, Stefan Gruenert, Marcus Hacker, Swen Hesse, Lukas Hofmann, Smilla Pusitz, Michael Rullmann, Osama Sabri, Roberto Sciagrà, Lalith Kumar Shiyam Sundar, Anke Tönjes, Hubert Wirtz, Josef Yu, Armin Frille

Background: Cancer-associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non-imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole-body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC.

Methods: This multi-centre study included 345 LCP who underwent WB [18F]FDG-PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into 'No CAC' (WLGS-0/1 at baseline prior treatment and at first follow-up: N = 158, 51F/107M), 'Dev CAC' (WLGS-0/1 at baseline and WLGS-3/4 at follow-up: N = 90, 34F/56M), and 'CAC' (WLGS-3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (aorta>) and CT-defined volumes were extracted for abdominal and visceral organs, muscles, and adipose-tissue using automated image segmentation of baseline [18F]FDG-PET/CT images. Imaging and non-imaging parameters from laboratory tests were compared statistically. A machine-learning (ML) model was then trained to classify LCP as 'No CAC', 'Dev CAC', and 'CAC' based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient.

Results: The three CAC categories displayed multi-organ differences in aorta>. In all target organs, aorta> was higher in the 'CAC' cohort compared with 'No CAC' (P < 0.01), except for liver and kidneys, where aorta> in 'CAC' was reduced by 5%. The 'Dev CAC' cohort displayed a small but significant increase in aorta> of pancreas (+4%), skeletal-muscle (+7%), subcutaneous adipose-tissue (+11%), and visceral adipose-tissue (+15%). In 'CAC' patients, a strong negative Spearman correlation (ρ = -0.8) was identified between aorta> and volumes of adipose-tissue. The machine-learning model identified 'CAC' at baseline with 81% of accuracy, highlighting aorta> of spleen, pancreas, liver, and adipose-tissue as most relevant features. The model performance was suboptimal (54%) when classifying 'Dev CAC' versus 'No CAC'.

Conclusions: WB [18F]FDG-PET/CT imaging reveals groupwise differences in the multi-organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients

背景:癌症相关恶病质(CAC)是一种导致肺癌患者(LCP)耐药和死亡的代谢综合征。CAC 通常使用临床非成像标准来定义。考虑到 CAC 的代谢基础以及[18F]氟-2-脱氧-D-葡萄糖(FDG)-正电子发射断层扫描(PET)/计算机断层扫描(CT)提供葡萄糖周转定量信息的能力,我们评估了全身(WB)PET/CT 成像作为 LCP 标准诊断检查的一部分在提供 CAC 发病或存在的额外信息方面的作用:这项多中心研究纳入了 345 名接受 WB [18F]FDG-PET/CT 成像检查以进行初步临床分期的 LCP 患者。根据体重指数调整的体重减轻分级系统(WLGS)将 LCP 分为 "无 CAC"(治疗前和首次随访时基线 WLGS-0/1:N = 158,51F/107M)、"Dev CAC"(基线 WLGS-0/1 和随访时 WLGS-3/4:N = 90,34F/56M)和 "CAC"(基线 WLGS-3/4:N = 97,31F/66M)。对于每个 CAC 类别,使用基线[18F]FDG-PET/CT 图像的自动图像分割,提取腹部和内脏器官、肌肉和脂肪组织的平均标准化摄取值 (SUV) 归一化为主动脉摄取值(主动脉>)和 CT 定义的体积。对来自实验室检测的成像和非成像参数进行了统计比较。然后训练机器学习(ML)模型,根据成像参数将 LCP 分为 "无 CAC"、"Dev CAC "和 "CAC"。采用SHAPLE Additive exPlanations (SHAP)分析来确定导致每位患者CAC发展的关键因素:结果:三类 CAC 在主动脉上显示出多器官差异。在所有目标器官中,与 "无 CAC "相比,"CAC "组群的主动脉>更高("CAC "组群的主动脉>降低了 5%)。Dev CAC "队列中,胰腺(+4%)、骨骼肌(+7%)、皮下脂肪组织(+11%)和内脏脂肪组织(+15%)的主动脉>有小幅但显著的增加。在 "CAC "患者中,主动脉>与脂肪组织体积之间存在强烈的 Spearman 负相关(ρ = -0.8)。机器学习模型识别基线 "CAC "的准确率为 81%,脾脏、胰腺、肝脏和脂肪组织的主动脉>是最相关的特征。在对 "Dev CAC "和 "No CAC "进行分类时,该模型的表现并不理想(54%):结论:WB[18F]FDG-PET/CT 成像揭示了有 CAC 和无 CAC 的 LCP 多器官代谢的组间差异,从而突显了慢性钙化患者的全身代谢异常症状。基于回顾性队列,我们的 ML 模型能准确识别 CAC 患者。然而,该模型在出现 CAC 的患者中的表现并不理想。我们已经启动了一项前瞻性多中心研究,以解决目前回顾性分析的局限性。
{"title":"Detection of cancer-associated cachexia in lung cancer patients using whole-body [<sup>18</sup>F]FDG-PET/CT imaging: A multi-centre study.","authors":"Daria Ferrara, Elisabetta M Abenavoli, Thomas Beyer, Stefan Gruenert, Marcus Hacker, Swen Hesse, Lukas Hofmann, Smilla Pusitz, Michael Rullmann, Osama Sabri, Roberto Sciagrà, Lalith Kumar Shiyam Sundar, Anke Tönjes, Hubert Wirtz, Josef Yu, Armin Frille","doi":"10.1002/jcsm.13571","DOIUrl":"https://doi.org/10.1002/jcsm.13571","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non-imaging criteria. Given the metabolic underpinnings of CAC and the ability of [<sup>18</sup>F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole-body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC.</p><p><strong>Methods: </strong>This multi-centre study included 345 LCP who underwent WB [<sup>18</sup>F]FDG-PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into 'No CAC' (WLGS-0/1 at baseline prior treatment and at first follow-up: N = 158, 51F/107M), 'Dev CAC' (WLGS-0/1 at baseline and WLGS-3/4 at follow-up: N = 90, 34F/56M), and 'CAC' (WLGS-3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (<SUV<sub>aorta</sub>>) and CT-defined volumes were extracted for abdominal and visceral organs, muscles, and adipose-tissue using automated image segmentation of baseline [<sup>18</sup>F]FDG-PET/CT images. Imaging and non-imaging parameters from laboratory tests were compared statistically. A machine-learning (ML) model was then trained to classify LCP as 'No CAC', 'Dev CAC', and 'CAC' based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient.</p><p><strong>Results: </strong>The three CAC categories displayed multi-organ differences in <SUV<sub>aorta</sub>>. In all target organs, <SUV<sub>aorta</sub>> was higher in the 'CAC' cohort compared with 'No CAC' (P < 0.01), except for liver and kidneys, where <SUV<sub>aorta</sub>> in 'CAC' was reduced by 5%. The 'Dev CAC' cohort displayed a small but significant increase in <SUV<sub>aorta</sub>> of pancreas (+4%), skeletal-muscle (+7%), subcutaneous adipose-tissue (+11%), and visceral adipose-tissue (+15%). In 'CAC' patients, a strong negative Spearman correlation (ρ = -0.8) was identified between <SUV<sub>aorta</sub>> and volumes of adipose-tissue. The machine-learning model identified 'CAC' at baseline with 81% of accuracy, highlighting <SUV<sub>aorta</sub>> of spleen, pancreas, liver, and adipose-tissue as most relevant features. The model performance was suboptimal (54%) when classifying 'Dev CAC' versus 'No CAC'.</p><p><strong>Conclusions: </strong>WB [<sup>18</sup>F]FDG-PET/CT imaging reveals groupwise differences in the multi-organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Body composition parameters in initial CT imaging of mechanically ventilated trauma patients: Single-centre observational study. 机械通气创伤患者初始 CT 成像中的身体成分参数:单中心观察研究。
IF 8.9 1区 医学 Pub Date : 2024-08-26 DOI: 10.1002/jcsm.13578
Hans-Jonas Meyer, Tihomir Dermendzhiev, Michael Hetz, Georg Osterhoff, Christian Kleber, Timm Denecke, Jeanette Henkelmann, Robert Werdehausen, Gunther Hempel, Manuel F Struck

Background: Body composition parameters provide relevant prognostic significance in critical care cohorts and cancer populations. Published results regarding polytrauma patients are inconclusive to date. The goal of this study was to analyse the role of body composition parameters in severely injured trauma patients.

Methods: All consecutive patients requiring emergency tracheal intubation and mechanical ventilation before initial computed tomography (CT) at a level-1 trauma centre over a 12-year period (2008-2019) were reanalysed. The analysis included CT-derived body composition parameters based upon whole-body trauma CT as prognostic variables for 30-day mortality, intensive care unit length of stay (ICU LOS) and mechanical ventilation duration.

Results: Four hundred seventy-two patients (75% male) with a median age of 49 years, median injury severity score of 26 and 30-day mortality rate of 22% (104 patients) met the inclusion criteria and were analysed. Regarding body composition parameters, 231 patients (49%) had visceral obesity, 75 patients had sarcopenia (16%) and 35 patients had sarcopenic obesity (7.4%). After adjustment for statistically significant univariable predictors age, body mass index, sarcopenic obesity, visceral obesity, American Society of Anesthesiologists classification ≥3, injury severity score and Glasgow Coma Scale ≤ 8 points, the Cox proportional hazard model identified sarcopenia as significant prognostic factor of 30-day mortality (hazard ratio 2.84; 95% confidence interval 1.38-5.85; P = 0.004), which was confirmed in Kaplan-Meier survival analysis (log-rank P = 0.006). In a subanalysis of 363 survivors, linear multivariable regression analysis revealed no significant associations of body composition parameters with ICU LOS and duration of mechanical ventilation.

Conclusions: In a multivariable analysis of mechanically ventilated trauma patients, CT-defined sarcopenia was significantly associated with 30-day mortality whereas no associations of body composition parameters with ICU LOS and duration of mechanical ventilation were observed.

背景:身体成分参数对重症监护人群和癌症患者的预后具有重要意义。迄今为止,已发表的有关多发性创伤患者的研究结果尚无定论。本研究旨在分析身体成分参数在严重创伤患者中的作用:重新分析了一家一级创伤中心在 12 年内(2008-2019 年)首次进行计算机断层扫描(CT)前需要紧急气管插管和机械通气的所有连续患者。分析包括基于全身创伤 CT 的 CT 导出身体成分参数,作为 30 天死亡率、重症监护室住院时间(ICU LOS)和机械通气持续时间的预后变量:符合纳入标准的 422 名患者(75% 为男性)(104 人)的中位年龄为 49 岁,中位受伤严重程度评分为 26 分,30 天死亡率为 22%。在身体组成参数方面,231 名患者(49%)患有内脏肥胖症,75 名患者患有肌肉疏松症(16%),35 名患者患有肌肉疏松性肥胖症(7.4%)。在对具有统计学意义的单变量预测因素年龄、体重指数、肌肉疏松性肥胖、内脏肥胖、美国麻醉医师协会分类≥3、损伤严重程度评分和格拉斯哥昏迷量表≤8 分进行调整后,Cox 比例危险模型确定肌肉疏松症是 30 天死亡率的重要预后因素(危险比 2.84; 95% 置信区间 1.38-5.85; P = 0.004),卡普兰-米尔生存分析证实了这一点(log-rank P = 0.006)。在对363名幸存者进行的一项子分析中,线性多变量回归分析显示,身体成分参数与重症监护室的住院时间和机械通气的持续时间没有明显关系:结论:在对接受机械通气的创伤患者进行的多变量分析中,CT定义的肌肉疏松症与30天死亡率明显相关,而身体成分参数与重症监护室的住院时间和机械通气时间没有关系。
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引用次数: 0
Factors associated with handgrip strength across the life course: A systematic review. 生命历程中与握力相关的因素:系统综述。
IF 8.9 1区 医学 Pub Date : 2024-08-26 DOI: 10.1002/jcsm.13586
Leticia W Ribeiro, Sara Berndt, Gregore I Mielke, Jenny Doust, Gita D Mishra

Background: Muscle strength is essential for healthy ageing. Handgrip strength (HGS) has been recommended by expert bodies as the preferred measure of muscle strength, in addition to being considered a strong predictor of overall health. Cross-sectional studies have shown several potential factors associated with HGS, but a systematic review of factors predicting HGS over time has not previously been conducted. The aim of this study is to systematically review the literature on the factors associated with adult HGS [at follow-up(s) or its rate of change] across the life course.

Methods: Searches were performed in MEDLINE via Ebsco, Embase and SPORTDiscus databases. Longitudinal studies assessing potential factors impacting adult HGS over time were included in the analyses. Based on previously established definitions of consistency of results, a semiquantitative analysis was conducted using the proportions of studies supporting correlations with HGS.

Results: A total of 117 articles were included in this review. Factors associated with HGS were grouped into 11 domains: demographic, socioeconomic, genetic, early life, body composition, health markers/biomarkers, health conditions, psychosocial, lifestyle, reproductive and environmental determinants. Overall, 103 factors were identified, of which 10 showed consistent associations with HGS over time (i.e., in at least four studies with ≥60% agreement in the direction of association). Factors associated with greater declines in HGS included increasing age, male sex, higher levels of inflammatory markers and the presence of cardiovascular diseases. Education level, medication use, and self-rated health were not associated with the rate of change in HGS. Increased birth weight was associated with a stronger HGS over time, whereas depressive symptoms were linked to a weaker HGS, and smoking habits showed null associations.

Conclusions: Comparison between studies and estimation of effect sizes were limited due to the heterogeneity in methods. Although sex and age may be the main drivers of HGS decline, it is crucial to prioritize modifiable factors such as inflammation and cardiovascular diseases in health interventions to prevent greater losses. Interventions to improve birth weight and mental health are also likely to produce positive effects on muscle strength. Our results point to the complexity of processes involving muscle strength and suggest that the need to better understand the determinants of HGS remains.

背景:肌肉力量对健康老龄化至关重要。手握力(HGS)已被专家机构推荐为衡量肌肉力量的首选指标,同时也被认为是预测整体健康的有力指标。横断面研究显示了与 HGS 相关的几个潜在因素,但此前尚未对预测 HGS 随时间变化的因素进行过系统回顾。本研究的目的是系统回顾与成人 HGS(随访时或其变化率)相关的文献:方法:通过 Ebsco、Embase 和 SPORTDiscus 数据库对 MEDLINE 进行检索。分析纳入了评估影响成人 HGS 随时间变化的潜在因素的纵向研究。根据之前确定的结果一致性定义,使用支持与 HGS 相关性的研究比例进行了半定量分析:本综述共收录了 117 篇文章。与 HGS 相关的因素分为 11 个领域:人口、社会经济、遗传、早期生活、身体成分、健康标志物/生物标志物、健康状况、社会心理、生活方式、生殖和环境决定因素。总体而言,共确定了 103 个因素,其中 10 个因素与 HGS 的长期关联性一致(即在至少四项研究中,关联方向的一致性≥60%)。与 HGS 下降幅度较大相关的因素包括年龄增加、男性、炎症标志物水平升高以及心血管疾病的存在。教育水平、药物使用和自我健康评价与 HGS 的变化率无关。出生体重的增加与HGS随时间推移而增强有关,而抑郁症状与HGS减弱有关,吸烟习惯与HGS无关联:结论:由于研究方法的异质性,研究间的比较和效应大小的估计受到了限制。虽然性别和年龄可能是HGS下降的主要驱动因素,但在健康干预中优先考虑炎症和心血管疾病等可改变的因素以防止更大的损失至关重要。改善出生体重和心理健康的干预措施也可能对肌肉力量产生积极影响。我们的研究结果表明了涉及肌肉力量的过程的复杂性,并表明仍有必要更好地了解 HGS 的决定因素。
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引用次数: 0
Exploring the utility of ultrasound to assess disuse atrophy in different muscles of the lower leg. 探索超声波评估小腿不同肌肉废用性萎缩的实用性。
IF 8.9 1区 医学 Pub Date : 2024-08-26 DOI: 10.1002/jcsm.13583
Edward J Hardy, Joseph J Bass, Thomas B Inns, Mathew Piasecki, Jessica Piasecki, Craig Sale, Robert H Morris, Jonathan N Lund, Ken Smith, Daniel J Wilkinson, Philip J Atherton, Bethan E Phillips

Background: Skeletal muscle is a highly plastic tissue crucial for many functions associated with whole-body health across the life course. Magnetic resonance imaging (MRI) is the current gold standard for measuring skeletal muscle size. However, MRI is expensive, and access to facilities is often limited. B-mode ultrasonography (U/S) has been proposed as a potential alternative to MRI for the assessment of muscle size. However, to date, no work has explored the utility of U/S to assess disuse muscle atrophy (DMA) across muscles with different atrophy susceptibility profiles, an omission which may limit the clinical application of previous work.

Methods: To address this significant knowledge gap, 10 young men (22 ±  years, 24.1 ± 2.3 kg/m2) underwent 15-day unilateral leg immobilization using a knee-brace and air boot. Cross-sectional area (CSA) and muscle thickness (MT) of the tibialis anterior (TA) and medial gastrocnemius (MG) were assessed via U/S before and after immobilization, with CSA and muscle volume assessed via MRI.

Results: With both muscles combined, there were good correlations between each U/S and MRI measure, both before (e.g., CSAMRI vs. MTU/S and CSAU/S: r = 0.88 and 0.94, respectively, both P < 0.0001) and after (e.g., VOLMRI vs. MTU/S and CSAU/S: r = 0.90 and 0.96, respectively, both P < 0.0001) immobilization. The relationship between the methods was notably stronger for MG than TA at each time-point (e.g., CSAMRI vs. MTU/S: MG, r = 0.70, P = 0.0006; TA, r = 0.37, P = 0.10). There was no relationship between the degree of DMA determined by the two methods in either muscle (e.g., TA pre- vs. post-immobilization, VOLMRI: 136 ± 6 vs. 133 ± 5, P = 0.08; CSAU/S: 6.05 ± 0.3 vs. 5.92 ± 0.4, P = 0.70; relationship between methods: r = 0.12, P = 0.75).

Conclusions: Both MTU/S and CSAU/S provide comparable static measures of lower leg muscle size compared with MRI, albeit with weaker agreement in TA compared to MG. Although both MTU/S and CSAU/S can discern differences in DMA susceptibility between muscles, neither can reliably assess degree of DMA. Based on the growing recognition of heterogeneous atrophy profiles between muscles, and the topical importance of less commonly studied muscles (i.e., TA for falls prevention in older adults), future research should aim to optimize accessible methods to determine muscle losses across the body.

背景:骨骼肌是一种可塑性很强的组织,对整个生命过程中与全身健康相关的许多功能至关重要。磁共振成像(MRI)是目前测量骨骼肌大小的黄金标准。然而,核磁共振成像价格昂贵,而且使用设施往往有限。有人建议用 B 型超声波(U/S)替代磁共振成像评估肌肉大小。然而,迄今为止,还没有任何研究探讨过 U/S在评估不同肌肉萎缩易感性的肌肉的废用性肌肉萎缩(DMA)方面的实用性,这一疏忽可能会限制之前研究的临床应用:为了填补这一重大知识空白,10 名年轻男性(22 ± 岁,24.1 ± 2.3 kg/m2)使用膝关节支架和气靴进行了为期 15 天的单侧腿部固定。在固定前后,通过U/S评估胫骨前肌(TA)和内侧腓肠肌(MG)的横截面积(CSA)和肌肉厚度(MT),并通过核磁共振成像评估CSA和肌肉体积:对于两块肌肉,U/S和MRI测量结果之间均存在良好的相关性(例如,CSAMRI vs. MTU/S和CSAU/S:r = 0.88和0.94;P MRI vs. MTU/S和CSAU/S:r = 0.90和0.96;P MRI vs. MTU/S:MG,r = 0.70,P = 0.0006;TA,r = 0.37,P = 0.10)。两种方法测定的两块肌肉的 DMA 程度之间没有关系(例如,固定前与固定后的 TA,VOLMRI:136 ± 6 vs. 133 ± 5,P = 0.08;CSAU/S:6.05 ± 0.3 vs. 5.92 ± 0.4,P = 0.70;两种方法之间的关系:r = 0.12,P = 0.75):结论:与核磁共振成像相比,MTU/S 和 CSAU/S 可提供具有可比性的小腿肌肉大小静态测量结果,尽管 TA 与 MG 的一致性较弱。虽然 MTU/S 和 CSAU/S 都能发现肌肉间 DMA 易感性的差异,但两者都不能可靠地评估 DMA 的程度。由于人们越来越认识到肌肉之间存在不同的萎缩特征,而且较少研究的肌肉(如用于预防老年人跌倒的 TA)具有重要的临床意义,因此未来的研究应致力于优化可用于确定全身肌肉损失的方法。
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引用次数: 0
Call for standardization in assessment and reporting of muscle and adipose change using computed tomography analysis in oncology: A scoping review 呼吁在肿瘤学中使用计算机断层扫描分析对肌肉和脂肪变化的评估和报告进行标准化:范围界定综述。
IF 8.9 1区 医学 Pub Date : 2023-09-07 DOI: 10.1002/jcsm.13318
Pamela N. Klassen, Vera C. Mazurak, Jessica Thorlakson, Stephane Servais
Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta‐analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative‐intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta‐analysis. Studies that measured computed tomography‐defined SM and/or AT change in adult patients during palliative‐intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2/m2, cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex‐specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta‐analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.
研究人员越来越多地测量癌症治疗期间骨骼肌(SM)和脂肪组织(AT)的变化,以了解对患者结果的影响。最近的荟萃分析报告了该文献中的高度异质性,代表了由此产生的估计的不确定性。以缓解期化疗为例,我们旨在系统总结评估癌症治疗期间SM和AT变化的研究的变异性来源,并为未来的研究提出标准,以实现可靠的荟萃分析。包括测量计算机断层扫描定义的成年患者在实体瘤姑息性化疗期间SM和/或AT变化的研究,没有日期或地理限制。在2496篇按摘要/标题筛选的出版物中,83篇为全文综述,38篇为摘录,代表了8个肿瘤部位的34个独特队列。基线测量的时间通常定义为治疗前,而终点时间从治疗开始后6周到进展时间不等。少于50%的人指定了测量之间的实际时间间隔。很少讨论测量误差(8/34)。在18/34队列中,使用单一指标(cm2/m2、cm2或%)来描述SM变化,而在10/34队列中使用了多个指标,在6/34队列中没有使用描述性指标。10/34队列的AT变化指标和性别特异性报告可用。在24篇出版物中评估了SM损失与总生存率之间的相关性,SM损失的分类从任何损失到变化时间间隔内损失>14%不等。年龄和性别是最常见的协变量,50%的模型有疾病反应。尽管有丰富的数据和努力,但研究设计、报告和统计分析的异质性阻碍了关于癌症治疗期间SM和AT变化的严重程度和结果的证据综合。研究设计的拟议标准包括同质队列的选择、基线/终点时间的明确定义以及对测量误差的关注。标准报告应包括按性别、实际扫描间隔、使用多种指标的SM和AT基线变化以及观察到的变化范围的可视化。按性别报告将促进对SM和AT变化中两性异形的理解。评估组织变化对结果的影响需要对相关协变量和并发疾病反应进行调整。研究人员和出版商采用这些标准将改变当前的范式,使未来的研究能够进行荟萃分析,并推动该领域将SM和AT变化有意义地应用于临床护理。
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引用次数: 0
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Journal of Cachexia, Sarcopenia and Muscle
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