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Body mass index and natriuretic peptides trends before and after left ventricular assist device 左心室辅助装置前后的体重指数和利钠肽趋势
JCSM rapid communications
Pub Date : 2023-03-18 DOI: 10.1002/rco2.76
Jessica Schultz, Amanda R. Vest, Maria Masotti, Austin Hoeg, Levi Teigen, Ranjit John, Andrew Shaffer, Tamas Alexy, Cindy Martin, Rebecca Cogswell

Background

It is unknown to what degree of sarcopenia related to heart failure (HF) is reversible with resolution of the HF syndrome. We evaluated whether (1) weight loss prior to left ventricular assist device (LVAD) is associated with pre-operative sarcopenia as quantified on pre-operative chest CTs and (2) determine the relationship between weight recovery (increase) after LVAD implantation and reduction of NT-proBNP levels.

Methods

In a large single-centre cohort (n = 502), CT measures of sarcopenia (pectoralis muscle mass indexed to body surface area and tissue attenuation) were correlated with pre-LVAD BMI trend (n = 190). BMI and NT-proBNP trends before and after LVAD implantation were evaluated (n = 403). Linear effects modelling was performed to test the association between NT-proBNP and BMI trends.

Results

A downtrending BMI prior to LVAD was associated with pectoralis muscle tissue attenuation (P < 0.05). BMI declined prior to LVAD, declined further early post-implant, and then increased between 100 and 300 days post-implant (average per cent change in BMI in Year 1, 7.6%, 95% CI: 6.3–8.8%). NT-proBNP decreased during the first 100 post LVAD days (−5.4%, 95% CI: −6.6 to −4.2%). Post-LVAD NT-proBNP and BMI trends were significantly associated, with a decrease of 1 unit log NT-proBNP associated with an increase in BMI of 0.81 kg/m2 (CI: 0.53–1.09, P < .001). The rise in post-LVAD BMI occurred after the reduction in NT-proBNP levels. Patients who failed to gain weight post-LVAD had the highest 6-month post-LVAD natriuretic peptides (lowest per cent BMI gain tertile NT-proBNP: 2208 vs. highest 1635 pg/mL, P < 0.001).

Conclusions

Weight recovery during LVAD support occurs after the reduction in natriuretic peptide levels. Failure to gain weight during LVAD support was associated with persistently elevated natriuretic peptide levels. These data collectively suggest that recovery of body mass may be dependent upon recovery of the HF syndrome.

目前尚不清楚与心力衰竭（HF）相关的少肌症在多大程度上可以逆转HF综合征。我们评估了（1）左心室辅助装置（LVAD）前的体重减轻是否与术前胸部CT量化的术前少肌症有关，以及（2）确定LVAD植入后体重恢复（增加）与NT-proBNP水平降低之间的关系。
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引用次数: 0
Different reversibility of skeletal muscle mass and strength in elderly Japanese women after the first wave of COVID-19 第一波COVID - 19后日本老年妇女骨骼肌质量和力量的不同可逆性
JCSM rapid communications
Pub Date : 2023-02-27 DOI: 10.1002/rco2.73
Bo-Kyung Son, Toshiyuki Imoto, Tomohiro Inoue, Takatoshi Nishimura, Weida Lyu, Tomoki Tanaka, Katsuya Iijima

Background

Restrictions on outdoor movements due to the coronavirus disease (COVID-19) pandemic have led to a decreased physical activity; this can lead to sarcopenia and frailty in older adults. Our recent study has demonstrated a significant decrease in the trunk muscle mass immediately after the pandemic's first wave (April–May 2020) among Japanese community-dwelling older women. In the present study, we further examined whether muscle mass recovery or deterioration occurs after 1 year of the pandemic's first wave by comparing physical measurements among the following assessment periods: before the first wave, immediately after the first wave, and at 1-year follow-up thereafter.

Methods

This study included 77 women (78.0 ± 5.7 years) who underwent physical measurements for muscle mass, grip strength, one-leg stand-up ability (3 s), and oral motor skills and answered questionnaires on sociality (social network, participation, and support) in the three assessment periods.

Results

The frequency of going out and the subjective vitality were significantly decreased immediately after the first wave; these recovered at the 1-year follow-up (P < 0.001). When comparing muscular measures, the trunk muscle mass index preferentially decreased immediately after the first wave but recovered significantly at the 1-year follow-up (P < 0.001). Conversely, the appendicular skeletal muscle mass index (ASMI) and grip strength continued to decrease until the 1-year follow-up (P < 0.001 and P = 0.03, respectively). The ability to perform a one-leg stand-up for 3 s and the oral motor skills did not change significantly across the assessment periods. The prevalence of pre-sarcopenia and sarcopenia tended to increase during these periods (P = 0.068). The reduction and subsequent recovery patterns for sociality were similar to those observed for the trunk muscle mass.

Conclusions

Our findings demonstrated differences in the reversibility of skeletal muscle mass and strength at 1 year after the first wave of the COVID-19 pandemic: the trunk muscle mass declined acutely and recovered rapidly, whereas the ASMI and grip strength declined continuously. These differences in the skeletal muscle recovery and deterioration might help formulate short-term or long-term strategies for COVID-19-related sarcopenia prevention in community-dwelling older adults.

冠状病毒病（COVID-19）大流行对户外活动的限制导致体育活动减少；这会导致老年人少肌症和虚弱。我们最近的研究表明，在第一波疫情（2020年4月至5月）后，居住在日本社区的老年女性的躯干肌肉量立即显著减少。在本研究中，我们通过比较以下评估期的身体测量结果，进一步检查了在第一波疫情爆发1年后肌肉质量是否恢复或恶化：第一波疫情之前、第一波疫情之后以及之后1年的随访。
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引用次数: 1
Patient-derived pancreatic tumour organoid implantation establishes novel pre-cachexia mouse models 患者源性胰腺肿瘤类器官植入建立了新的前恶病质小鼠模型
JCSM rapid communications
Pub Date : 2022-11-03 DOI: 10.1002/rco2.71
Merel R. Aberle, Rianne D.W. Vaes, Wouter R.P.H. van de Worp, Ludwig J. Dubois, Natasja G. Lieuwes, Rianne Biemans, Ramon C.J. Langen, Frederik-Jan van Schooten, Ronald M. van Dam, Steven W.M. Olde Damink, Sander S. Rensen

Background

The poor survival of pancreatic cancer patients is largely attributable to cachexia, a syndrome of severe weight and muscle loss. To investigate the aetiology of cancer cachexia, preclinical models that closely recapitulate the human disease process are essential. Patient derived tumour organoids are promising novel cancer models, but their ability to induce cachexia in mice has not been investigated. We developed two pancreatic tumour organoid-based mouse models and demonstrate their potential for cancer cachexia research.

Methods

Two patients with pancreatic cancer, from whom tumour organoid cultures were previously established, were selected based on their cachexia phenotype. Patient 09 was characterized as cachectic according to the international consensus definition of cancer cachexia, whereas patient 12 was classified as non-cachectic. Organoid cultures PANCO-09b and PANCO-12a in basement membrane extract (BME) were injected subcutaneously into the flanks of 9-weeks old NMRI-Foxn1nu mice (n = 8/group). A control group was injected with BME only (n = 4). Body weight was monitored every 2–3 days for 38 days. Hind limb muscle wet and dry weights were measured. Adipocyte size in inguinal white adipose tissue was measured using haematoxylin and eosin-stained sections. Expression of genes associated with cancer cachexia in muscle and liver tissue was analysed using qPCR.

Results

Engraftment of tumour organoids was successful in 87.5% of PANCO-09b implanted mice and in 50% of PANCO-12a mice, with similar average tumour weights at endpoint (34.4 ± 25.1 mg vs. 32.8 ± 40.2 mg, respectively, P = 0.450). All groups initially gained weight, but PANCO-12a implanted mice progressively lost an average body weight of 1.7 ± 0.8 g from day 28 onwards. PANCO-12a-implanted mice gained significantly less weight from baseline than controls (0.7 ± 0.6 g, P = 0.027). Overall body weight gain of PANCO-09b mice was also lower but not significantly different from controls (2.0 ± 1.2 g vs. 2.9 ± 1.6 g, P = 0.961). Wet weights of hind leg muscles were negatively correlated with tumour weight but did not differ between groups. Adipocytes of PANCO-12a implanted mice were smaller compared to SHAM as well as PANCO09b mice (P < 0.0001), indicative of white adipose tissue wasting.

Conclusions

Implantation of human pancreatic tumour organoids into mice negati

胰腺癌患者的低生存率主要归因于恶病质，这是一种严重体重和肌肉损失的综合征。为了研究癌症恶病质的病因，密切概括人类疾病过程的临床前模型是必不可少的。患者来源的肿瘤类器官是很有前途的新型癌症模型，但它们在小鼠体内诱导恶病质的能力尚未得到研究。我们开发了两种基于胰腺肿瘤类器官的小鼠模型，并证明了它们在癌症恶病质研究中的潜力。
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引用次数: 0
Risedronate use may blunt appendicular lean mass loss secondary to sleeve gastrectomy: results from a pilot randomized controlled trial 利塞膦酸钠的使用可能会减轻袖式胃切除术后阑尾瘦肿块的损失:一项随机对照试验的结果
JCSM rapid communications
Pub Date : 2022-10-14 DOI: 10.1002/rco2.72
Laura E. Flores, Kristen M. Beavers, Daniel P. Beavers, Katelyn A. Greene, Diana A. Madrid, Ryan M. Miller, Jamy D. Ard, Laura D. Bilek, Ashley A. Weaver

Background

Despite robust weight loss and cardiometabolic benefit, lean mass loss following sleeve gastrectomy (SG) confers health risk. Bisphosphonates are a potential therapeutic agent for lean mass maintenance. Thus, our objective was to explore the effect of 6 months of risedronate (vs. placebo) on change in dual-energy x-ray absorptiometry (DXA)- and computed tomography (CT)-derived lean mass metrics in the year following SG.

Methods

Twenty-four SG patients were randomized to 6 months of 150-mg oral risedronate or placebo capsules (NCT03411902). Body composition was assessed at baseline and 6 months with optional 12-month follow-up using whole-body DXA and CT at the lumbar spine and mid-thigh. Group treatment effects and 95% confidence intervals (CIs) were generated from a mixed model using contrast statements at 6 and 12 months, adjusted for baseline values.

Results

Of 24 participants enrolled [55.7 ± 6.7 years (mean ± SD), 79% Caucasian, 83% women, body mass index (BMI) 44.7 ± 6.3 kg/m2], 21 returned for 6-month testing and 14 returned for 12-month testing. Six-month weight loss was −16.3 kg (−20.0, −12.5) and −20.9 kg (−23.7, −18.1) in the risedronate and placebo groups, respectively (P = 0.057). Primary analysis at 6 months revealed a non-significant sparing of appendicular lean mass in the risedronate group compared with placebo [−1.2 kg (−2.3, −0.1) vs. −2.1 kg (−3.0, −1.2)]; P = 0.20. By 12 months, the risedronate group displayed no change in appendicular lean mass from baseline [−0.5 kg (−1.5, 0.6)]; however, the placebo group experienced significantly augmented loss [−2.9 kg (−3.6, −2.1)].

Conclusions

Pilot data indicate that risedronate treatment may mitigate appendicular lean mass loss following SG. Further study is warranted.

背景:尽管有显著的体重减轻和心脏代谢益处，但袖式胃切除术(SG)后的瘦体重减少会带来健康风险。双膦酸盐是维持瘦肉质量的潜在治疗剂。因此，我们的目的是探讨6个月的利塞膦酸钠(与安慰剂相比)对SG后一年双能x射线吸收测定(DXA)和计算机断层扫描(CT)衍生的瘦质量指标变化的影响。方法24例SG患者随机接受150 mg口服利塞膦酸酯或安慰剂胶囊(NCT03411902)治疗6个月。在基线和6个月时评估身体组成，并可选择12个月的随访，使用腰椎和大腿中部的全身DXA和CT。组治疗效果和95%置信区间(ci)由混合模型生成，使用6个月和12个月时的对比陈述，并根据基线值进行调整。结果入选的24名参与者[55.7±6.7岁(平均±SD)， 79%高加索人，83%女性，体重指数(BMI) 44.7±6.3 kg/m2]， 21人返回进行6个月的检测，14人返回进行12个月的检测。利塞膦酸钠组和安慰剂组6个月的体重减轻分别为- 16.3 kg(- 20.0， - 12.5)和- 20.9 kg (- 23.7， - 18.1) (P = 0.057)。6个月时的初步分析显示，与安慰剂相比，利塞酮组阑尾瘦质量无显著减少[- 1.2 kg(- 2.3， - 0.1)对- 2.1 kg (- 3.0， - 1.2)];p = 0.20。12个月时，利塞膦酸钠组阑尾瘦质量与基线相比没有变化[- 0.5 kg (- 1.5, 0.6)];然而，安慰剂组的体重损失显著增加[- 2.9 kg(- 3.6， - 2.1)]。结论初步数据表明，利塞膦酸钠治疗可减轻SG后阑尾瘦质量损失。值得进一步研究。
{"title":"Risedronate use may blunt appendicular lean mass loss secondary to sleeve gastrectomy: results from a pilot randomized controlled trial","authors":"Laura E. Flores,&nbsp;Kristen M. Beavers,&nbsp;Daniel P. Beavers,&nbsp;Katelyn A. Greene,&nbsp;Diana A. Madrid,&nbsp;Ryan M. Miller,&nbsp;Jamy D. Ard,&nbsp;Laura D. Bilek,&nbsp;Ashley A. Weaver","doi":"10.1002/rco2.72","DOIUrl":"10.1002/rco2.72","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite robust weight loss and cardiometabolic benefit, lean mass loss following sleeve gastrectomy (SG) confers health risk. Bisphosphonates are a potential therapeutic agent for lean mass maintenance. Thus, our objective was to explore the effect of 6 months of risedronate (vs. placebo) on change in dual-energy x-ray absorptiometry (DXA)- and computed tomography (CT)-derived lean mass metrics in the year following SG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four SG patients were randomized to 6 months of 150-mg oral risedronate or placebo capsules (NCT03411902). Body composition was assessed at baseline and 6 months with optional 12-month follow-up using whole-body DXA and CT at the lumbar spine and mid-thigh. Group treatment effects and 95% confidence intervals (CIs) were generated from a mixed model using contrast statements at 6 and 12 months, adjusted for baseline values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 24 participants enrolled [55.7 ± 6.7 years (mean ± SD), 79% Caucasian, 83% women, body mass index (BMI) 44.7 ± 6.3 kg/m<sup>2</sup>], 21 returned for 6-month testing and 14 returned for 12-month testing. Six-month weight loss was −16.3 kg (−20.0, −12.5) and −20.9 kg (−23.7, −18.1) in the risedronate and placebo groups, respectively (<i>P</i> = 0.057). Primary analysis at 6 months revealed a non-significant sparing of appendicular lean mass in the risedronate group compared with placebo [−1.2 kg (−2.3, −0.1) vs. −2.1 kg (−3.0, −1.2)]; <i>P</i> = 0.20. By 12 months, the risedronate group displayed no change in appendicular lean mass from baseline [−0.5 kg (−1.5, 0.6)]; however, the placebo group experienced significantly augmented loss [−2.9 kg (−3.6, −2.1)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pilot data indicate that risedronate treatment may mitigate appendicular lean mass loss following SG. Further study is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 1","pages":"18-25"},"PeriodicalIF":0.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.72","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9583542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risedronate or Exercise for Lean Mass Preservation During Menopause: Secondary Analysis of a Randomized Controlled Trial. 利塞膦酸钠或运动对更年期瘦体重的保护作用：随机对照试验的二次分析。
JCSM rapid communications
Pub Date : 2022-07-01 Epub Date: 2022-03-09 DOI: 10.1002/rco2.59
Laura E Flores, Kevin Kupzyk, Nancy Waltman, Kristen M Beavers, Laura Bilek

Background: The menopause transition is marked by hormonal shifts leading to body composition changes, such as fat mass gain and lean mass loss. Weight-bearing and resistance exercise can help maintain lean mass during the menopause transition; however, uptake is low. Pre-clinical research points to bisphosphonates as also being effective in preventing loss of lean mass. Thus, we sought to investigate whether bisphosphonate therapy can mitigate loss of lean mass and outperform weight-bearing exercise in the years immediately following menopause.

Methods: Data come from the Heartland Osteoporosis Prevention Study (NCT02186600), where osteopenic, postmenopausal women were randomized to bisphosphonate (n=91), weight-bearing/resistance exercise (n=92), or control (n=93) conditions over a one-year period. Dual energy X-ray absorptiometry (DXA)-derived body composition measures (including total lean mass, total fat mass, lean mass index, and lean mass-to-fat mass ratio) were ascertained at baseline, six, and 12-months. Adherence to risedronate and weight-bearing exercise was defined as the percentage of dosages taken and exercise sessions attended. Intent-to-treat analysis using linear modeling was used to generate treatment effects on body composition. Secondary analysis utilized per-protocol analysis and included adjustment for weight change.

Results: 276 women (age: 54.5 years; 83.3% Caucasian; BMI: 25.7 kg/m2) were included in the analyses. 12-month adherence to the risedronate and exercise interventions was 89% and 64%, respectively. Group-by-time interactions were observed for lean mass, revealing exercise (0.43±1.49kg) and risedronate groups (0.31±1.68 kg) gained significantly more lean mass than control (-0.15±1.27 kg) over 12-months. However, after controlling for weight change in secondary analysis, the difference in lean mass change between control and risedronate became non-significant (p=0.059).

Conclusions: Results suggest both 12 months of oral risedronate and 12 months of weight-bearing exercise may diminish lean mass loss experienced during the menopause transition as compared to control. The lean mass sparing effect for risedronate may be driven by overall weight change.

背景：绝经过渡期的特点是荷尔蒙变化导致身体成分发生变化，如脂肪量增加和瘦肉量减少。负重和阻力运动有助于在更年期过渡期间保持瘦体重；然而，这种运动的吸收率很低。临床前研究表明，双膦酸盐也能有效防止瘦体重的减少。因此，我们试图研究双膦酸盐疗法是否能在绝经后的几年内减轻瘦体重的流失，并优于负重运动：方法：数据来自心脏地带骨质疏松症预防研究（NCT02186600），在该研究中，骨质疏松的绝经后妇女被随机分配到双膦酸盐（91 人）、负重/阻力运动（92 人）或对照组（93 人），为期一年。在基线、6 个月和 12 个月期间，对双能 X 射线吸收测定法（DXA）得出的身体成分测量结果（包括总瘦肉质量、总脂肪质量、瘦肉质量指数和瘦肉质量与脂肪质量比）进行确认。利塞膦酸盐和负重锻炼的依从性定义为服用剂量和参加锻炼次数的百分比。采用线性建模的意向治疗分析产生了对身体成分的治疗效果。结果：276 名女性（年龄：54.5 岁；83.3% 白种人；体重指数：25.7 kg/m2）被纳入分析。利塞膦酸盐和运动干预12个月的坚持率分别为89%和64%。在瘦体重方面观察到了组间时间交互作用，显示运动组（0.43±1.49 千克）和利塞膦酸钠组（0.31±1.68 千克）在 12 个月内增加的瘦体重明显高于对照组（-0.15±1.27 千克）。然而，在二次分析中控制体重变化后，对照组和利塞膦酸钠组的瘦体重变化差异变得不显著（P=0.059）：结果表明，与对照组相比，口服利塞膦酸钠 12 个月和负重锻炼 12 个月可减少绝经过渡期的瘦体重减轻。利塞膦酸钠的瘦体重减少效应可能是由整体体重变化驱动的。
{"title":"Risedronate or Exercise for Lean Mass Preservation During Menopause: Secondary Analysis of a Randomized Controlled Trial.","authors":"Laura E Flores, Kevin Kupzyk, Nancy Waltman, Kristen M Beavers, Laura Bilek","doi":"10.1002/rco2.59","DOIUrl":"10.1002/rco2.59","url":null,"abstract":"<p><strong>Background: </strong>The menopause transition is marked by hormonal shifts leading to body composition changes, such as fat mass gain and lean mass loss. Weight-bearing and resistance exercise can help maintain lean mass during the menopause transition; however, uptake is low. Pre-clinical research points to bisphosphonates as also being effective in preventing loss of lean mass. Thus, we sought to investigate whether bisphosphonate therapy can mitigate loss of lean mass and outperform weight-bearing exercise in the years immediately following menopause.</p><p><strong>Methods: </strong>Data come from the Heartland Osteoporosis Prevention Study (NCT02186600), where osteopenic, postmenopausal women were randomized to bisphosphonate (n=91), weight-bearing/resistance exercise (n=92), or control (n=93) conditions over a one-year period. Dual energy X-ray absorptiometry (DXA)-derived body composition measures (including total lean mass, total fat mass, lean mass index, and lean mass-to-fat mass ratio) were ascertained at baseline, six, and 12-months. Adherence to risedronate and weight-bearing exercise was defined as the percentage of dosages taken and exercise sessions attended. Intent-to-treat analysis using linear modeling was used to generate treatment effects on body composition. Secondary analysis utilized per-protocol analysis and included adjustment for weight change.</p><p><strong>Results: </strong>276 women (age: 54.5 years; 83.3% Caucasian; BMI: 25.7 kg/m<sup>2</sup>) were included in the analyses. 12-month adherence to the risedronate and exercise interventions was 89% and 64%, respectively. Group-by-time interactions were observed for lean mass, revealing exercise (0.43±1.49kg) and risedronate groups (0.31±1.68 kg) gained significantly more lean mass than control (-0.15±1.27 kg) over 12-months. However, after controlling for weight change in secondary analysis, the difference in lean mass change between control and risedronate became non-significant (<i>p=0.059</i>).</p><p><strong>Conclusions: </strong>Results suggest both 12 months of oral risedronate and 12 months of weight-bearing exercise may diminish lean mass loss experienced during the menopause transition as compared to control. The lean mass sparing effect for risedronate may be driven by overall weight change.</p>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"5 2","pages":"154-161"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517955/pdf/nihms-1778461.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9729676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of circulating plasma ceramides as a potential sexually dimorphic biomarker of pancreatic cancer-induced cachexia. 循环血浆神经酰胺作为胰腺癌诱导恶病质的潜在性二型生物标志物的鉴定。
JCSM rapid communications
Pub Date : 2022-07-01 Epub Date: 2022-06-20 DOI: 10.1002/rco2.68
Jeffery M Chakedis, Mary E Dillhoff, Carl R Schmidt, Priyani V Rajasekera, David C Evans, Terence M Williams, Denis C Guttridge, Erin E Talbert

Background: Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared to cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes.

Methods: Targeted metabolomics, that included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n=10/group, equally divided by sex). Additional patient samples were analyzed (total n=95) and Receiver Operating Characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia.

Results: Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males.

Conclusions: Our findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.

背景：与没有体重减轻的癌症患者相比，表现出恶病质的癌症患者体重减轻，治疗耐受性低，预后差。尽管患者的风险明显增加，但恶病质的诊断仍然经常依赖于自我报告的体重减轻。识别癌症恶病质患者的可靠生物标志物将是改善临床决策和识别有不良后果风险的患者的有价值工具。方法：对确诊患有和不患有恶病质的胰腺导管腺癌（PDAC）患者和未患有癌症的对照患者的血浆样本进行靶向代谢组学研究，包括氨基酸、三羧酸、脂肪酸、酰基肉碱和鞘脂。分析了额外的患者样本（总n=95），并进行了受试者操作特征（ROC）分析，以确定是否有任何代谢物可以有效地作为恶病质的生物标志物。结果：靶向分析显示，与非恶病质PDAC患者或无癌症患者相比，恶病质患者的三种鞘脂循环水平降低。C18神经酰胺与C24神经酰胺的比例（C18:C24）优于其他一些先前提出的恶病质生物标志物（ROC=0.810）。值得注意的是，包括C18:C24在内的一些生物标志物仅在恶病质男性中发生改变。结论：我们的研究结果将C18:C24确定为PDAC诱导的恶病质的潜在新生物标志物，这也突出了癌症恶病质中先前未被重视的性别二型。
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引用次数: 0
MRI thigh measurements predict whole‐body skeletal muscle mass in patients with type 2 diabetes: a comparison with DXA MRI大腿测量预测2型糖尿病患者全身骨骼肌质量：与DXA的比较
JCSM rapid communications
Pub Date : 2022-07-01 DOI: 10.1002/rco2.70
E. Brown, A. Williams, O. Hakim, M. Wilton, J. Harrold, David Hughes, G. Kemp, J. Wilding, L. Goff, D. Cuthbertson
Sarcopenia is an age‐related loss of skeletal muscle mass (SMM) and function, associated with falls, frailty, and functional decline. It is more prevalent and often accelerated in people with Type 2 diabetes (T2D), especially when co‐existing with obesity (sarcopenic obesity). Accurate whole‐body SMM measurement, feasible using dual‐energy X‐ray absorptiometry (DXA) or magnetic resonance imaging (MRI), has utility both in clinical practice and in epidemiological and mechanistic research, considering the dual mechanical and metabolic function of skeletal muscle. Compared with MRI, DXA may underestimate age‐related muscle mass by up to 30%, and so direct comparison of DXA/MRI‐derived SMM measurements may be invalid in patients with obesity and T2D, who have potentially even more pronounced sarcopenia/sarcopenic obesity. We aimed to validate single‐slice or multiple‐slice measures of SMM, using MRI, with whole‐body SMM measures derived from DXA scans of appendicular lean soft tissue, specifically in patients with obesity and T2D.
肌萎缩是一种与年龄相关的骨骼肌质量（SMM）和功能丧失，与跌倒、虚弱和功能下降有关。它在2型糖尿病（T2D）患者中更为普遍，并且经常加速，尤其是当与肥胖（肌萎缩性肥胖）共存时。考虑到骨骼肌的双重机械和代谢功能，使用双能X射线吸收仪（DXA）或磁共振成像（MRI）进行准确的全身SMM测量是可行的，在临床实践以及流行病学和机制研究中都有实用性。与MRI相比，DXA可能低估了高达30%的与年龄相关的肌肉质量，因此直接比较DXA/MRI衍生的SMM测量结果在肥胖和T2D患者中可能无效，因为他们可能有更明显的少肌症/少肌性肥胖。我们的目的是使用MRI验证SMM的单层或多层测量，以及来自阑尾瘦软组织DXA扫描的全身SMM测量，特别是在肥胖和T2D患者中。
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引用次数: 0
Rescue of a peroxisome proliferator activated receptor gamma gene network in muscle after growth of human breast tumour xenografts 人乳腺肿瘤异种移植物生长后肌肉中过氧化物酶体增殖物激活受体γ基因网络的拯救
JCSM rapid communications
Pub Date : 2022-06-30 DOI: 10.1002/rco2.69
David A. Stanton, Hannah E. Wilson, Matthew G. Chapa, J. Link, Kristin Lupinacci, W. Geldenhuys, E. Pistilli
Fatigue is common in patents with breast cancer (BC), and can occur in patients with early stage disease and in the absence of muscle wasting (i.e. cachexia). We have reported transcriptional and proteomic alterations in muscles from BC patients, which are associated with fatigue. Mice implanted with human BC xenografts recapitulate the muscle molecular composition changes seen in patients, coupled with a greater rate of contraction‐induced fatigue. Multiple bioinformatics platforms in both human and mouse muscles have identified peroxisome proliferator activated receptor gamma (PPARG) as central to this phenotype, with several PPARG target genes downregulated in muscle in response to tumour growth. The current study tested the hypothesis that the PPARG agonist pioglitazone (pio), a commonly prescribed diabetes drug, would rescue the transcriptional alterations observed in muscles of tumour‐bearing mice.
疲劳在患有癌症（BC）的患者中很常见，并且可能发生在早期疾病和没有肌肉萎缩（即恶病质）的患者身上。我们已经报道了BC患者肌肉的转录和蛋白质组学改变，这与疲劳有关。植入人类BC异种移植物的小鼠重现了患者肌肉分子组成的变化，同时出现了更高的收缩诱导疲劳率。人类和小鼠肌肉中的多个生物信息学平台已确定过氧化物酶体增殖物激活受体γ（PPARG）是该表型的核心，肌肉中的几个PPARG靶基因因肿瘤生长而下调。目前的研究验证了PPARG激动剂吡格列酮（pio）（一种常见的糖尿病处方药）可以挽救在荷瘤小鼠肌肉中观察到的转录改变的假设。
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引用次数: 0
Muscle mass change using linear measurement analysis after nephrectomy for pT3 and pT4 renal cell carcinoma is associated with mortality pT3和pT4肾细胞癌切除术后肌肉质量变化与死亡率相关
JCSM rapid communications
Pub Date : 2022-06-15 DOI: 10.1002/rco2.66
A. Medline, Eric Midenberg, Dattatraya Patil, Sean T. Evans, N. Vettikattu, F. Kamal, K. Ogan, S. Psutka, M. Bilen, V. Master
Preoperative skeletal muscle deficiency is an established risk factor for poor survival outcomes in patients with renal cell carcinoma (RCC). However, given the dynamic nature of skeletal muscle associated with malignancy, there is a need to evaluate the prognostic benefit of muscle area change from the preoperative to postoperative period. We hypothesize that an improvement in muscle area following nephrectomy, measured by linear segmentation of L3 psoas and paraspinal musculature, is associated with improvement in overall survival (OS) and cancer specific survival (CSS) for patients with pT3 and pT4 RCC.
术前骨骼肌缺乏是肾细胞癌（RCC）患者生存结果不佳的一个既定风险因素。然而，鉴于骨骼肌与恶性肿瘤相关的动态性质，有必要评估从术前到术后肌肉面积变化的预后益处。我们假设，通过L3腰大肌和脊旁肌肉组织的线性分割测量，肾切除术后肌肉面积的改善与pT3和pT4肾细胞癌患者的总生存率（OS）和癌症特异性生存率（CSS）的改善有关。
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引用次数: 1
Human primary skeletal muscle‐derived myoblasts and fibroblasts reveal different senescent phenotypes 人类原发性骨骼肌来源的成肌细胞和成纤维细胞显示出不同的衰老表型
JCSM rapid communications
Pub Date : 2022-06-14 DOI: 10.1002/rco2.67
Thomas G. Francis, O. Jaka, G. Ellison‐Hughes, N. Lazarus, S. Harridge
The age‐related loss of muscle mass and quality, sarcopenia, has many contributing factors, one of which may be cellular senescence, but this is not well defined in human skeletal muscle.
与年龄相关的肌肉质量和质量损失，即少肌症，有许多促成因素，其中之一可能是细胞衰老，但这在人类骨骼肌中尚不明确。
{"title":"Human primary skeletal muscle‐derived myoblasts and fibroblasts reveal different senescent phenotypes","authors":"Thomas G. Francis, O. Jaka, G. Ellison‐Hughes, N. Lazarus, S. Harridge","doi":"10.1002/rco2.67","DOIUrl":"https://doi.org/10.1002/rco2.67","url":null,"abstract":"The age‐related loss of muscle mass and quality, sarcopenia, has many contributing factors, one of which may be cellular senescence, but this is not well defined in human skeletal muscle.","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"5 1","pages":"226 - 238"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44143484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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