JCSM rapid communications最新文献_第3页

Muscle Loss Is Prevalent and Severe in the ICU: An Analysis of Clinically Acquired CT Images 肌肉损失是普遍和严重的ICU：临床获得的CT图像分析

JCSM rapid communications

Pub Date : 2025-04-09 DOI: 10.1002/rco2.70004

Ainsley C. J. Smith, Brandon M. Hisey, Chel Hee Lee, Christopher J. Grant, Richard E. A. Walker, Kevin J. Solverson, Kirsten N. Bott, Christopher J. Doig, Sarah L. Manske

Background

Muscle loss is a common and debilitating complication of critical illness. Understanding the prevalence, severity, and risk factors associated with muscle loss is challenging. Muscle cross-sectional area obtained from computed tomography (CT) scans can be used to assess changes in muscle over the course of critical illness. The objective of this study was to investigate changes in muscle in the ICU using clinically acquired CT imaging, describe the severity and prevalence of muscle loss in the ICU, and explore the risk factors for muscle loss in the ICU.

Methods

For this multi-hospital cohort study, we acquired baseline and follow-up CT abdominal scans for 171 ICU trauma and sepsis patients from four hospitals in Calgary, Canada. We measured mean psoas muscle cross-sectional area at the level of the third lumbar vertebra using a U-Net algorithm and manual correction. Patient demographic and illness-related information were acquired using electronic medical records. Linear mixed models and regressions were used to assess risk factors.

Results

CT-derived psoas muscle index (PMI, defined as psoas cross-sectional area/height²), was calculated for 151 patients. The median [IQR] age was 55 [42, 67] years and 40% of patients were female. 71% of patients had sepsis and 29% had traumatic injuries. Patients experienced a median [IQR] 9 [1.5, 18.3]% reduction in psoas muscle index (PMI) over a median [IQR] 13 [9, 21] days in the ICU. This represents a median PMI loss rate of 0.9% [0.2, 1.6] % per day. The prevalence of substantial PMI loss (≥ 10%) was 45%. Patients with greater PMI at baseline or greater time in the ICU experienced more profound PMI loss (p < 0.001). Trauma patients experienced a greater rate of PMI loss than sepsis patients (p < 0.05). Female sepsis patients had the lowest PMI at follow-up (p < 0.001). 89% of patients survived the ICU. Greater rate of PMI loss was associated with increased ICU mortality (p < 0.05).

Conclusions

Muscle loss in trauma and sepsis patients in the ICU is common, especially among patients with longer ICU stays or greater baseline muscle. Greater rate of muscle loss occurs in trauma patients and is associated with mortality.

背景：肌肉萎缩是危重症的常见并发症。了解与肌肉损失相关的患病率、严重程度和危险因素是具有挑战性的。通过计算机断层扫描（CT）获得的肌肉横截面积可用于评估危重疾病过程中肌肉的变化。本研究的目的是通过临床获得的CT影像来研究ICU患者的肌肉变化，描述ICU患者肌肉损失的严重程度和流行程度，并探讨ICU患者肌肉损失的危险因素。方法在这项多医院队列研究中，我们获得了来自加拿大卡尔加里四家医院的171例ICU创伤和败血症患者的基线和随访CT腹部扫描。我们使用U-Net算法和人工校正测量了第三腰椎水平的腰大肌平均横截面积。使用电子病历获取患者人口统计和疾病相关信息。使用线性混合模型和回归来评估危险因素。结果计算了151例患者的ct腰肌指数（PMI，定义为腰肌横截面积/高度2）。中位[IQR]年龄为55岁[42,67]岁，40%的患者为女性。71%的患者有败血症，29%的患者有外伤性损伤。患者在ICU的中位[IQR] 13[9,21]天内腰肌指数（PMI）下降了9[1.5,18.3]%。这意味着平均每天的PMI损失率为0.9%[0.2,1.6]%。PMI大幅下降（≥10%）的发生率为45%。基线时PMI较高或在ICU住院时间较长的患者会经历更严重的PMI损失（p < 0.001）。创伤患者的PMI丢失率高于脓毒症患者（p < 0.05）。女性脓毒症患者随访时PMI最低（p < 0.001）。89%的患者在ICU存活。PMI失失率越高，ICU死亡率越高（p < 0.05）。结论：ICU创伤和脓毒症患者的肌肉损失是常见的，特别是在ICU住院时间较长或基线肌肉较大的患者中。创伤患者的肌肉损失率更高，并与死亡率相关。

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引用次数: 0

Muscle atrophy in osteoarthritis: clinical features, pathological changes, underlying mechanisms, and exercise-based interventions 骨关节炎的肌肉萎缩：临床特征、病理改变、潜在机制和基于运动的干预

JCSM rapid communications

Pub Date : 2025-03-29 DOI: 10.1002/rco2.99

Tongyi Zhang, Bin Zhang, Jinhui Wu, Song Li, Yunquan Gong, Shunzheng Fang, Daibo Feng, Bo Huang, Jiqin Lian, Wei Xiang, Lin Chen, Zhenhong Ni

Background

Osteoarthritis (OA) is a common degenerative disease with cartilage injury as the core pathological phenotype, which has become the leading cause of disability in the elderly. Skeletal muscle is an important organ to maintain the structure and motor function of joints, which is highly related to OA progress. Patients with OA typically exhibit abnormalities in the skeletal muscles surrounding the joints, such as reduced muscle mass and strength. We refer to this condition as OA-related muscle atrophy (hereafter referred to as OAMA). The mechanisms of OAMA are multifactorial and unclear.

Methods

In this narrative review, we summarized relevant research progress of OAMA (i) to review the changes in skeletal muscle of patients with OA, (ii) to review the underlying biological mechanisms of OAMA, (iii) to review the effects of skeletal muscle on OA, and (iv) to provide perspectives on current and potential strategies of OA clinical treatment based on skeletal muscle, especially exercise training.

Results

OAMA may lead to the destruction of joint stability and cartilage homeostasis and then promote the occurrence and development of OA. Clinical manifestations of OAMA are a decline in muscle mass and strength and an abnormal movement pattern. The underlying biological mechanisms of OAMA include chronic inflammation, oxidative stress, ion metabolism, glycolipid metabolism, and epigenetics. The effects of skeletal muscle on OA are skeletal muscle-mediated cartilage damage via biomechanics, muscle-derived secretions, and muscle-derived stem cells.

Conclusions

More preclinical and clinical studies are imperative to study the mechanisms of OAMA and develop potential strategies. We hope that more studies can focus on the skeletal muscle during the OA process, which will be beneficial for delaying OA progression and improving the motor function of OA patients in the future.

骨关节炎（Osteoarthritis， OA）是一种常见的以软骨损伤为核心病理表型的退行性疾病，已成为老年人致残的首要原因。骨骼肌是维持关节结构和运动功能的重要器官，与骨关节炎的进展密切相关。骨性关节炎患者通常表现为关节周围骨骼肌异常，如肌肉质量和力量减少。我们将这种情况称为oa相关性肌肉萎缩（以下简称OAMA）。OAMA的机制是多因素的，目前尚不清楚。方法在本文中，我们对骨骼肌的相关研究进展进行综述(1)综述骨骼肌在OA患者中的变化，(2)综述骨骼肌在OA中的潜在生物学机制，(3)综述骨骼肌在OA中的作用，(4)对骨骼肌在OA临床治疗中的现有和潜在策略进行展望。尤其是运动训练。结果骨性关节炎可导致关节稳定性和软骨稳态的破坏，进而促进骨性关节炎的发生和发展。OAMA的临床表现是肌肉质量和力量的下降以及异常的运动模式。OAMA的潜在生物学机制包括慢性炎症、氧化应激、离子代谢、糖脂代谢和表观遗传学。骨骼肌对骨性关节炎的影响是通过生物力学、肌肉源性分泌物和肌肉源性干细胞介导的骨骼肌介导的软骨损伤。结论需要更多的临床前和临床研究来研究OAMA的机制和制定潜在的策略。我们希望更多的研究关注OA过程中的骨骼肌，这将有利于未来延缓OA进展，改善OA患者的运动功能。

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引用次数: 0

Effects of Pemafibrate on Serum Carnitine and Plasma Myostatin in Patients With Metabolic Dysfunction Associated Steatotic Liver Disease 培马巴贝特对代谢功能障碍相关脂肪变性肝病患者血清肉碱和血浆肌生长抑制素的影响

JCSM rapid communications

Pub Date : 2025-03-26 DOI: 10.1002/rco2.70002

Ryohei Tanigawa, Atsushi Nakajima, Yuichiro Eguchi, Hirokazu Takahashi, Rohit Loomba, Hideki Suganami, Masaya Tanahashi, Hidenori Arai

<div> <section> <h3> Background</h3> <p>Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator (SPPARMα), has positive effects on liver-related markers (e.g., liver stiffness determined by magnetic resonance elastography and alanine aminotransferase) in the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Patients with MASLD reportedly have a high rate of muscle mass loss; hence, the prevention and treatment of sarcopenia is important for patients with MASLD. PPARα may be involved in the expression of carnitine and myostatin, which are known muscle-related markers. We conducted a post-hoc analysis of the PEMA-FL study to investigate the effects of pemafibrate on carnitine and myostatin levels.</p> </section> <section> <h3> Methods</h3> <p>The PEMA-FL study, a double-blind, placebo-controlled, randomized, multicenter, Phase 2 trial, randomized 118 patients to either Pemafibrate 0.4 mg/day or placebo (1:1) group (orally, twice daily for 72 weeks). This post-hoc analysis examined the percentage change in total carnitine, free carnitine, acylcarnitine, and myostatin in the pemafibrate group compared to those in the placebo group. We examined the correlation between percentage changes in carnitine and myostatin levels.</p> </section> <section> <h3> Results</h3> <p>Pmafibrate significantly increased serum total carnitine and free carnitine levels from baseline compared to placebo at Week 48 (treatment difference 24.2%; <i>p</i> < 0.001, 27.3%; <i>p</i> < 0.001, respectively) with similar trends for serum acylcarnitine (treatment difference 10.7%). Pemafibrate significantly reduced plasma myostatin levels at Week 72 (treatment difference −11.0%; <i>p</i> < 0.01) from baseline. Analysis of the significant changes in free carnitine and myostatin levels by subgroups showed similar changes in almost all subgroups. The percent changes in the serum total carnitine, free carnitine and acylcarnitine, and plasma myostatin levels at 12 weeks demonstrated no obvious correlations (<i>r</i> = 0.337, <i>r</i> = 0.358, <i>r</i> = 0.077, respectively).</p> </section> <section> <h3> Conclusions</h3> <p>Pemafibrate increased the serum carnitine and decreased plasma myostatin levels in patients with MASLD, which may have potential application in the development and progression of sarcopenia, but there are no results on the effect on muscle mass. Further research is warranted to determine whether these changes in physiology can lead to clinical benefits in the prevention or treatmen

背景：在代谢功能障碍相关脂肪变性肝病（MASLD）患者的pama - fl研究中，Pemafibrate是一种选择性过氧化物酶体增殖物激活受体α (PPARα)调节剂（SPPARMα），对肝脏相关标志物（例如，通过磁共振弹性成像和丙氨酸转氨酶测定的肝脏硬度）具有积极作用。据报道，MASLD患者的肌肉质量损失率很高；因此，预防和治疗肌少症对MASLD患者至关重要。PPARα可能参与肉碱和肌肉生长抑制素的表达，这是已知的肌肉相关标志物。我们对pama - fl研究进行了事后分析，以调查培马布特对肉碱和肌肉生长抑制素水平的影响。poma - fl研究是一项双盲、安慰剂对照、随机、多中心、2期试验，118例患者随机分为poma - fl组（0.4 mg/d）和安慰剂组（1:1）（口服，每日2次，持续72周）。这个事后分析检查了与安慰剂组相比，培马哌特组中总肉毒碱、游离肉毒碱、酰基肉毒碱和肌肉生长抑制素的百分比变化。我们检查了肉毒碱和肌肉生长抑制素水平百分比变化之间的相关性。结果在第48周，与安慰剂相比，pmafitate显著增加了血清总肉毒碱和游离肉毒碱水平(治疗差异24.2%；P < 0.001, 27.3%；P < 0.001)，血清酰基肉碱的趋势相似（治疗差异为10.7%）。在第72周，培马哌特显著降低血浆肌生长抑制素水平(治疗差异为- 11.0%；P < 0.01)。分析各组游离肉碱和肌肉生长抑制素水平的显著变化，发现几乎所有亚组的变化都相似。血清总肉毒碱、游离肉毒碱和酰基肉毒碱与血浆肌生长抑制素在12周的变化百分比无明显相关性（r = 0.337, r = 0.358, r = 0.077）。结论培马菲特可提高MASLD患者血清肉碱水平，降低血浆肌生成抑制素水平，可能在肌少症的发生发展中有潜在的应用价值，但对肌肉质量的影响尚无结果。需要进一步的研究来确定这些生理变化是否能在预防或治疗MASLD患者肌肉减少症方面带来临床益处。试验注册：ClinicalTrials.gov标识符：NCT03350165。

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引用次数: 0

Correction to “Overexpression of thioredoxin-2 attenuates age-related muscle loss by suppressing mitochondrial oxidative stress and apoptosis” 更正“硫氧还蛋白-2的过度表达通过抑制线粒体氧化应激和细胞凋亡来减轻与年龄相关的肌肉损失”

JCSM rapid communications

Pub Date : 2025-03-24 DOI: 10.1002/rco2.70003

Tang, H., Kim, M., Lee, M., Baumann, K., Olguin, F., He, H., Wang, Y., Jiang, B., Fang, S., Zhu, J., Wang, K., Xia, H., Gao, Y., Konsker, H. B., Fatodu, E. A., Quarta, M., Blonigan, J., Rando, T. A., and Shrager, J. B. (2022) Overexpression of thioredoxin-2 attenuates age-related muscle loss by suppressing mitochondrial oxidative stress and apoptosis. JCSM Rapid Communications, 5: 130–145, https://doi.org/10.1002/rco2.57.

We failed to include funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR73248) to TAR in the Acknowledgements.

We apologize for this error.

Tang， H., Kim， M., Lee， M., Baumann， K., Olguin， F., He， H., Wang， Y., Jiang， B., Fang， S., Zhu， J., Wang， K., Xia， H., Gao， Y., Konsker， H. B., Fatodu， E. A., Quarta， M., Blonigan， J., Rando， T. A., Shrager， J.（2022）过表达的硫氧还蛋白-2通过抑制线粒体氧化应激和细胞凋亡来减轻年龄相关的肌肉损失。快速通信，5:130-145,https://doi.org/10.1002/rco2.57。我们没有在致谢中包括来自国家关节炎、肌肉骨骼和皮肤疾病研究所（R01 AR73248）对TAR的资助。我们为这个错误道歉。

引用次数: 0

Malnutrition Risk and the Psychological Burden of Anorexia and Cachexia in Patients With Advanced Cancer 晚期癌症患者厌食症和恶病质的营养不良风险及心理负担

JCSM rapid communications

Pub Date : 2025-03-19 DOI: 10.1002/rco2.70001

Rony Dev, Patricia Bramati, Marvin Omar Delgado Guay, Bryan Fellman, Ahsan Azhar, Michael Tang, Jegy Tennison, Josue Becerra, Sonal Admane, Shalini Dalal, David Hui, Egidio Del Fabbro, Eduardo Bruera

Background

Patients with advanced cancer are at risk for malnutrition and anorexia-cachexia syndrome. The study objective was to determine the frequency of these conditions in patients evaluated in an outpatient supportive care clinic (SCC).

Methods

One hundred patients with cancer were prospectively enrolled to complete a cross-sectional one-time survey. We collected patient demographics, cancer diagnosis, weight history and height and Zubrod performance status from electronic health records. Patients completed the Functional Assessment of Anorexia Therapy–Anorexia/Cachexia Subscale (FAACT-A/CS) questionnaire, the Edmonton Symptom Assessment Scale (ESAS), the Patient-Generated Subjective Global Assessment–Short Form (PG-SGA-SF), the Hospital Anxiety and Depression Scale (HADS) and a Body Image Scale (BIS). A PG-SGA-SF cut-off of ≥ 6 indicated malnutrition risk, and loss of appetite was defined as either ESAS ≥ 3 or FAACT-ACS ≤ 37.

Results

Of the 165 patients approached, 100 (61%) completed the survey. The average (SD) age was 61.6 years old (11.5). The majority were female (52%), White (75%) and married (80%). The most common cancers were gastrointestinal (22%) and genitourinary (21%). Sixty-one per cent (61%) screened positive for risk of malnutrition (PG-SGA-SF ≥ 6), anorexia was noted in 60% (ESAS ≥ 3) and 53% (FAACT-A/CS ≤ 37) of patients, 10% of patients were noted to have a body mass index < 18.5, and 28% had body image dissatisfaction (BIS ≥ 10). Documented > 5% weight loss over the past 6 months was noted in 49%; 61% noted > 10% lifetime weight loss, relative to usual adult body weight or at time of diagnosis. Patients with anorexia (FAACT-ACS ≤ 37) compared with no anorexia reported significantly higher HADS anxiety score (4.4 vs. 3.2, p = 0.04), depression (5.9 vs. 3.5, p = 0.001), body image distress (BIS 7.2 vs. 4.9, p = 0.03) and worse appetite (ESAS 1.4 vs. 0.6, p = 0.02). Symptoms including depression, anxiety and body image distress were not significantly different between patients with either a history of > 10% lifetime weight loss or > 5% weight loss over 6 months.

Conclusions

Malnutrition risk was noted in roughly 60% of patients with advanced cancer. Inclusion of patients' body mass index to malnutrition or cachexia criteria resulted in underdiagnosis. Subjective symptoms of anorexia, but not objective weight loss, was significantly associated w

晚期癌症患者存在营养不良和厌食症-恶病质综合征的风险。研究目的是确定在门诊支持护理诊所（SCC）评估的患者中这些情况的频率。方法对100例癌症患者进行前瞻性横断面一次性调查。我们从电子健康记录中收集患者人口统计资料、癌症诊断、体重史、身高和Zubrod性能状态。患者完成厌食症治疗功能评估-厌食症/恶病质子量表（FAACT-A/CS）问卷、埃德蒙顿症状评估量表（ESAS）、患者主观整体评估简表（PG-SGA-SF）、医院焦虑抑郁量表（HADS）和身体形象量表（BIS）。PG-SGA-SF临界值≥6表明存在营养不良风险，而食欲减退定义为ESAS≥3或FAACT-ACS≤37。结果165例患者中，100例（61%）完成了调查。平均（SD）年龄为61.6岁（11.5岁）。大多数是女性（52%），白人（75%）和已婚（80%）。最常见的癌症是胃肠道（22%）和泌尿生殖系统（21%）。61%（61%）的筛查结果为营养不良（PG-SGA-SF≥6），60% （ESAS≥3）和53% （FAACT-A/CS≤37）的患者存在厌食症，10%的患者存在体重指数18.5,28%的患者存在身体形象不满意（BIS≥10）。49%的人在过去6个月内体重减轻了5%；61%的患者表示，与正常成人体重或诊断时相比，终生体重减轻10%。与无厌食症患者相比，厌食症患者（FAACT-ACS≤37）的HADS焦虑评分（4.4比3.2,p = 0.04）、抑郁评分（5.9比3.5,p = 0.001）、身体形象困扰评分（BIS 7.2比4.9,p = 0.03）和食欲差评分（ESAS 1.4比0.6,p = 0.02）显著高于无厌食症患者。包括抑郁、焦虑和身体形象困扰在内的症状在终生体重减轻10%或6个月内体重减轻5%的患者之间没有显著差异。结论：大约60%的晚期癌症患者存在营养不良风险。将患者的体重指数纳入营养不良或恶病质标准导致诊断不足。主观厌食症症状与焦虑和抑郁显著相关，而非客观体重减轻。应将PG-SGA-SF常规营养不良筛查纳入所有门诊SCC就诊，并将当前体重与记录的病前基线体重进行比较，以确定恶病质的严重程度。

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引用次数: 0

Linking Circulating Irisin and Type 2 Diabetes: A Systematic Review and Meta-Analysis 循环鸢尾素与2型糖尿病的联系：一项系统综述和荟萃分析

JCSM rapid communications

Pub Date : 2025-03-13 DOI: 10.1002/rco2.70000

E. Aminov, P. Folan, A. Pisconti

<div> <section> <h3> Background</h3> <p>Type II diabetes (T2DM) is one of the most prevalent metabolic disorders, and its multisystemic health consequences are widely known. Due to skeletal muscle's ability to sequester a vast amount of glucose, muscle function and exercise have become a subject of much research into strategies to prevent and treat T2DM. Myokines are bioactive molecules released by muscle during contraction and involved in several biological processes such as metabolism, inflammation and behaviour. Irisin, a recently discovered myokine, has been implicated in a vast array of physiological roles, including the ability to induce fat beiging. Since beige and brown fat both serve important roles in metabolic regulation, irisin's role in the context of T2DM is the subject of ongoing investigations.</p> </section> <section> <h3> Methods</h3> <p>We systematically reviewed articles indexed in PubMed, Scopus and Web of Science that were published between 2011 and 2024 and compared circulating irisin levels in patients affected by T2DM and healthy subjects. As part of our systematic review of the literature, we performed meta-analysis of the data across all included articles, as well as stratified by body mass index (BMI), country of origin and by average irisin concentration in the control group.</p> </section> <section> <h3> Results</h3> <p>We discovered great variability across the included studies in the average irisin levels detected, which spanned four orders of magnitude, hence the attempt at reducing variability by stratifying based on average levels in the control group. While the statistical power of our meta-analysis was decreased by the great variability in reported irisin concentrations, we nonetheless detected a consistent trend of decreased irisin concentration in T2DM patients compared with healthy controls, regardless of BMI, country of origin or average irisin concentration in the control group.</p> </section> <section> <h3> Conclusions</h3> <p>With almost 60 articles included, ours is the first extensive systematic review and meta-analysis of irisin in T2DM, yet a highly statistically significant association between circulating irisin levels and T2DM could not be established due to the great variability of the data across include articles. Nonetheless, we noticed a trend that is independent of BMI, suggesting a direct relationship between T2DM and irisin that is likely not secondary to diabetic sarcopenia. While our work encourages further research into irisin's potential role in T2DM pathogenesis, the reproducibility of i

2型糖尿病（T2DM）是最常见的代谢性疾病之一，其多系统健康后果已广为人知。由于骨骼肌具有隔离大量葡萄糖的能力，肌肉功能和锻炼已成为预防和治疗2型糖尿病策略研究的主题。肌因子是肌肉在收缩过程中释放的生物活性分子，参与多种生物过程，如代谢、炎症和行为。鸢尾素是最近发现的一种肌肉生长因子，与一系列生理作用有关，包括诱导脂肪增加的能力。由于米色和棕色脂肪都在代谢调节中起重要作用，因此鸢尾素在T2DM中的作用是正在进行的研究的主题。方法系统回顾2011年至2024年间发表在PubMed、Scopus和Web of Science上的文章，比较T2DM患者和健康受试者的循环鸢尾素水平。作为文献系统回顾的一部分，我们对所有纳入文章的数据进行了荟萃分析，并按体重指数（BMI）、原产国和对照组的平均鸢尾素浓度进行了分层。结果我们发现，在所纳入的研究中，鸢尾素的平均检测水平存在很大的可变性，这跨越了四个数量级，因此我们试图通过基于对照组的平均水平分层来减少可变性。虽然我们的荟萃分析的统计能力因报告的鸢尾素浓度的巨大差异而降低，但我们仍然发现，与健康对照组相比，T2DM患者的鸢尾素浓度下降的趋势是一致的，而与对照组的BMI、原产国或平均鸢尾素浓度无关。我们的研究纳入了近60篇文章，这是第一次对鸢尾素在T2DM中的作用进行广泛的系统回顾和荟萃分析，但由于所纳入文章的数据差异很大，因此无法确定循环鸢尾素水平与T2DM之间具有高度统计学意义的关联。尽管如此，我们注意到一种独立于BMI的趋势，表明2型糖尿病和鸢尾素之间存在直接关系，而这种关系可能不是继发于糖尿病性肌肉减少症。虽然我们的工作鼓励进一步研究鸢尾素在2型糖尿病发病机制中的潜在作用，但鸢尾素检测方法在生物样本中的可重复性应该确定，并且应该为研究和临床社区提供标准化的方案。

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引用次数: 0

Low Muscle Mass and Treatment Tolerance in Patients With Upper Gastrointestinal Cancer: A Systematic Review and Meta-Analysis 上消化道肿瘤患者的低肌肉量和治疗耐受性：一项系统综述和荟萃分析

JCSM rapid communications

Pub Date : 2025-02-17 DOI: 10.1002/rco2.115

E. N. Stanhope, S. N. Thomsen, J. E. Turner, C. M. Fairman, I. M. Lahart

Background

Upper gastrointestinal (GI) cancers carry notable mortality risks. While systemic therapies are vital for their management, they are often hindered by adverse events (AE), which can compromise their effectiveness. The presence of low skeletal muscle mass (LSMM) may be linked with the prevalence of AE and could potentially undermine treatment tolerance by impacting drug metabolism. The primary objective of this systematic review and meta-analysis was to evaluate the association between LSMM and the risk of grades 3 and 4 AE and treatment discontinuation.

Methods

Studies investigating the association between skeletal muscle mass and AE or treatment tolerability in adult patients diagnosed with upper GI cancer scheduled to undergo systemic treatment were eligible. The primary outcomes were grades 3 and 4 AE and treatment discontinuations. Four electronic databases were systematically searched with no date restrictions on 10 October 2022. Data were analysed via random-effects meta-analyses, and the risk of bias was assessed using the risk of bias in non-randomised studies—of exposure (ROBINS-E) appraisal tool.

Results

We identified 50 eligible publications from 49 studies. Our meta-analyses revealed evidence of a higher risk of grades 3 and 4 AE (RR 1.44, 95% CI 1.23–1.68, N = 13) and treatment discontinuation (RR 2.39, 95% CI 1.87–3.07, N = 11) in LSMM versus non-LSMM. Secondary analyses revealed an increased risk of fatigue, febrile neutropenia, intestinal pneumonia, stomatitis and thrombocytopenia in LSMM. However, 92% of studies assessing grades 3 and 4 AE and 73% of studies examining treatment discontinuation had a very high risk of bias.

Conclusions

LSMM in patients with upper GI cancer is associated with a higher risk of grades 3 and 4 AE and the discontinuation of systemic cancer treatment. The high risk of bias should be considered in the interpretation of these findings. Further evaluation of the association between LSMM and treatment tolerability in confirmatory, prospective studies is needed.

背景：上胃肠道（GI）癌症具有显著的死亡风险。虽然全身治疗对其治疗至关重要，但它们经常受到不良事件（AE）的阻碍，这可能会损害其有效性。低骨骼肌质量（LSMM）的存在可能与AE的流行有关，并可能通过影响药物代谢而潜在地破坏治疗耐受性。本系统综述和荟萃分析的主要目的是评估LSMM与3级和4级AE风险和停止治疗之间的关系。方法研究骨骼肌质量与计划接受全身治疗的成年上消化道癌症患者AE或治疗耐受性之间的关系。主要结局是3级和4级AE和停止治疗。在2022年10月10日系统地检索了四个电子数据库，没有日期限制。通过随机效应荟萃分析分析数据，并使用非随机暴露研究（ROBINS-E）评估工具评估偏倚风险。结果：我们从49项研究中筛选出50篇符合条件的出版物。我们的荟萃分析显示，与非LSMM相比，LSMM患者发生3级和4级AE的风险更高（RR 1.44, 95% CI 1.23-1.68, N = 13），停药风险更高（RR 2.39, 95% CI 1.87-3.07, N = 11）。二次分析显示，LSMM患者出现疲劳、发热性中性粒细胞减少症、肠道肺炎、口炎和血小板减少症的风险增加。然而，92%评估3级和4级AE的研究和73%检查停止治疗的研究具有非常高的偏倚风险。结论：上消化道肿瘤患者的LSMM与3级和4级AE及停止全身癌症治疗的高风险相关。在解释这些发现时应考虑到高偏倚风险。需要在验证性的前瞻性研究中进一步评估LSMM与治疗耐受性之间的关系。

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引用次数: 0

Intramuscular CMT-167 Tumours Produce a Mild Cachexia Phenotype in C57BL/6J Mice C57BL/6J小鼠肌内CMT-167肿瘤产生轻度恶病质表型

JCSM rapid communications

Pub Date : 2025-02-06 DOI: 10.1002/rco2.117

Bryan C. Remaily, Trang T. Vu, Justin Thomas, Kyeongmin Kim, Camille Stanton, Zhiliang Xie, Lauren Granchie, Millennium Manna, Paul Gregorevic, Xiaokui Mo, Jeovanna Lowe, Jill A. Rafael-Fortney, Samuel K. Kulp, Latha P. Ganesan, Dwight H. Owen, Thomas A. Mace, Christopher C. Coss, Mitch A. Phelps

<div> <section> <h3> Background</h3> <p>Cancer cachexia is a debilitating syndrome characterized by irreversible losses in skeletal muscle mass, with or without losses in adipose tissue. Cancer cachexia is an underrecognized syndrome that impacts ~50% of all cancer patients and accounts for up to ~20% of all cancer deaths. Lung cancer remains one of the deadliest cancers in the United States with an estimated 137 000 deaths in the year 2021 alone. Lung cancer is highly comorbid with cancer cachexia. Pre-clinical models are heavily relied upon to study both lung cancer and cancer cachexia; however, there is a need to develop novel models to study the relationship between the two diseases. We therefore characterized the cachexia phenotype in the CMT-167 syngeneic lung cancer model.</p> </section> <section> <h3> Methods</h3> <p>Male C57BL6/J mice, aged 8–10 weeks, were administered an intramuscular (IM) injection of either 0.5 × 10<sup>6</sup> CMT-167 cells or vehicle. Clinically relevant features of cancer cachexia were assessed 23 days after CMT-167 cell administration in tumour bearing mice by assessment of terminal skeletal muscle and adipose tissue mass, gastrocnemius myofiber cross sectional area (CSA), circulating biomarkers of cachexia, and skeletal muscle E3 ubiquitin ligase mRNA. A single intravenous dose pharmacokinetic study of pembrolizumab was completed to assess tumour status influence upon antibody pharmacokinetics.</p> </section> <section> <h3> Results</h3> <p>Compared to tumour free (TF) mice, we observed lower terminal tumour-adjusted bodyweight, adipose tissue mass, gastrocnemius mass, quadriceps mass, and gastrocnemius myofiber CSA. CMT-167 tumour bearing (TB) mice did not lose bodyweight relative to starting weight, but instead failed to gain as much weight as TF controls. CMT-167 TB mice exhibited increased concentrations of circulating markers of cachexia and muscle wasting, such as IL-6 and TNF-<i>α</i>, although there was no difference in transcription of E3 ubiquitin ligases <i>Trim63</i> (MuRF-1) and <i>Fbxo32</i> (atrogin-1) in skeletal muscle compared to TF mice. CMT-167 TB mice exhibited increased catabolic clearance (CL) of the human IgG4 anti-PD-1, pembrolizumab, agreeing with published literature showing increased CL of immune checkpoint inhibitors in cachectic populations. Comparing the IM CMT-167 model to historical data with the well-established IM Lewis Lung Carcinoma model, CMT-167 TB mice displayed a less severe cachectic phenotype in terms of bodyweight and skeletal muscle effects.</p> </section> <section> <h3> Conclusions</h3>

癌症恶病质是一种使人衰弱的综合征，其特征是骨骼肌质量的不可逆损失，伴有或不伴有脂肪组织的损失。癌症恶病质是一种未被充分认识的综合征，影响着约50%的癌症患者，占所有癌症死亡人数的约20%。肺癌仍然是美国最致命的癌症之一，仅在2021年估计就有13.7万人死亡。肺癌与癌症恶病质高度合并症。研究肺癌和癌症恶病质严重依赖临床前模型；然而，有必要开发新的模型来研究这两种疾病之间的关系。因此，我们在CMT-167同基因肺癌模型中表征了恶病质表型。方法8 ~ 10周龄雄性C57BL6/J小鼠肌内注射0.5 × 106 CMT-167细胞或对照物。用CMT-167细胞治疗荷瘤小鼠23天后，通过评估骨骼肌和脂肪组织质量、肠肌肌纤维横截面面积（CSA）、恶病质循环生物标志物和骨骼肌E3泛素连接酶mRNA，评估癌症恶病质的临床相关特征。完成了单次静脉给药派姆单抗的药代动力学研究，以评估肿瘤状态对抗体药代动力学的影响。结果与无肿瘤小鼠（TF）相比，我们观察到下末端肿瘤调整体重、脂肪组织质量、腓肠肌质量、股四头肌质量和腓肠肌肌纤维CSA。CMT-167荷瘤（TB）小鼠的体重相对于初始体重并没有减轻，而是没有像TF对照组那样增加那么多的体重。与TF小鼠相比，CMT-167结核小鼠的骨骼肌中E3泛素连接酶Trim63 （MuRF-1）和Fbxo32 （atrorogin -1）的转录没有差异，但循环中恶病质和肌肉萎缩标志物，如IL-6和TNF-α的浓度增加。CMT-167结核小鼠对人IgG4抗pd -1 pembrolizumab的分解代谢清除率（CL）增加，这与已发表的文献显示在病毒质人群中免疫检查点抑制剂的CL增加一致。将IM CMT-167模型与历史数据与已建立的IM Lewis肺癌模型进行比较，CMT-167 TB小鼠在体重和骨骼肌效应方面表现出较轻的恶病质表型。结论IM CMT-167模型为轻度恶病质肺癌同基因模型。CMT-167结核小鼠是研究肺癌背景下癌症恶病质诱导、骨骼肌萎缩和免疫检查点抑制剂清除机制的新模型。

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引用次数: 0

A Dynamic Time Warping Extension to Consensus Weight-Based Cachexia Criteria Improves Prediction of Cancer Patient Outcomes 一个动态时间扭曲扩展到共识的基于体重的恶病质标准提高了癌症患者预后的预测

JCSM rapid communications

Pub Date : 2025-01-29 DOI: 10.1002/rco2.107

Noah Forrest, Steven Tran, Khizar R. Nandoliya, Ethan J. Houskamp, Tomasz Gruchala, Vijeeth Guggilla, Zequn Sun, Rimas Lukas, Derek Wainwright, Al'ona Furmanchuk, Jodi L. Johnson, Ishan Roy, Theresa L. Walunas

<div> <section> <h3> Background</h3> <p>Cachexia is a complex syndrome that impacts up to half of patients with cancer. Criteria systems have been developed for the purpose of diagnosing and grading cachexia severity in clinical settings. One of the most widely known is those developed by Fearon et al. in 2011, which utilizes body mass loss and body mass index (BMI) to determine the presence and extent of cachexia. One limitation of this system and other clinical cachexia scales is the lack of systematic methods for assessing cachexia severity longitudinally. We sought to develop an extension to the 2011 consensus criteria that categorizes cancer patients with respect to their temporal cachexia progression and assess its predictive capacity relative to the current time-agnostic system.</p> </section> <section> <h3> Methods</h3> <p>Two cancer cohorts were identified in electronic health record data: lung cancer and glioblastoma. We extracted weight and BMI measures from the time of cancer diagnosis until death or loss to follow-up and computed cachexia severity according to the consensus criteria. Subgroups of cachexia progression were uncovered using dynamic time warping (DTW) followed by unsupervised clustering. This system and baseline consensus criteria measurements were each assessed for their ability to stratify patient outcomes utilizing Kaplan–Meier curves and Cox proportional hazards and subsequently compared with model concordance and inverse probability of censoring weighting (IPCW).</p> </section> <section> <h3> Results</h3> <p>Significant differences were observed in overall survival Kaplan–Meier curves of 1023 patients with lung cancer when stratified by baseline cachexia classification (<i>p</i> = 0.0002, N events = 592) but not in a cohort of 545 patients with glioblastoma (<i>p</i> = 0.16, N events = 353). DTW uncovered three patterns of cachexia progression in each subgroup with features described as ‘smouldering’, ‘rapid with recovery’ or ‘persistent/recurrent’. Significant differences were observed in Kaplan–Meier curves when stratified by cachexia longitudinal patterns in lung cancer (<i>p</i> < 0.0001) and glioblastoma (<i>p</i> < 0.0001). Adjusted hazards ratios comparing the ‘persistent/recurrent’ cluster to referent subgroups in Cox models were 4.8 (4.1–5.8, <i>p</i> < 0.05) and 1.9 (1.4–2.4, <i>p</i> < 0.05) among patients with lung cancer and glioblastoma, respectively. Areas under the curve at multiple time points and Cox model concordances were greater when patients were stratified by progression pattern compared with baseline consensus criteria.</p> </section> <section

恶病质是一种复杂的综合征，影响着多达一半的癌症患者。标准系统已经开发的目的是诊断和分级恶病质严重程度在临床设置。其中最广为人知的是由Fearon等人在2011年开发的，它利用体重损失和身体质量指数（BMI）来确定恶病质的存在和程度。该系统和其他临床恶病质量表的一个局限性是缺乏纵向评估恶病质严重程度的系统方法。我们试图对2011年共识标准进行扩展，该标准对癌症患者的时间恶病质进展进行分类，并评估其相对于当前时间不可知系统的预测能力。方法在电子健康记录数据中确定两个癌症队列：肺癌和胶质母细胞瘤。我们提取了从癌症诊断到死亡或失去随访的体重和BMI测量值，并根据共识标准计算恶病质严重程度。使用动态时间翘曲（DTW）和无监督聚类来揭示恶病质进展的亚组。利用Kaplan-Meier曲线和Cox比例风险分别评估该系统和基线共识标准测量方法对患者结果分层的能力，随后与模型一致性和审查加权逆概率（IPCW）进行比较。结果1023例肺癌患者的总体生存Kaplan-Meier曲线在基线恶病质分类中观察到显著差异（p = 0.0002， N事件= 592），但在545例胶质母细胞瘤患者队列中观察到无显著差异（p = 0.16， N事件= 353）。DTW在每个亚组中发现了三种恶病质进展模式，其特征被描述为“闷烧”、“快速恢复”或“持续/复发”。当肺癌（p < 0.0001）和胶质母细胞瘤（p < 0.0001）以恶病质纵向模式分层时，Kaplan-Meier曲线有显著差异。在Cox模型中，肺癌和胶质母细胞瘤患者的“持续性/复发性”聚类与参考亚组的校正风险比分别为4.8 （4.1-5.8,p < 0.05）和1.9 （1.4-2.4,p < 0.05）。与基线共识标准相比，当患者按进展模式分层时，多个时间点的曲线下面积和Cox模型一致性更大。结论：我们的研究结果表明，以系统的方式考虑恶病质的纵向进展可以提高广泛使用的共识标准集的预后能力。这些发现对于未来在临床环境中识别恶病质进展模式的系统发展和帮助临床医生在恶病质相关决策方面具有重要意义。

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引用次数: 0

Creatinine Muscle Index as a Novel Muscle Mass Indicator in Patients With Chronic Kidney Disease 肌酐肌指数作为一种新的慢性肾病患者肌肉质量指标

JCSM rapid communications

Pub Date : 2025-01-13 DOI: 10.1002/rco2.116

Hiroki Nobayashi, Go Kanzaki, Aoi Okubo, Nobuo Tsuboi, Takashi Yokoo

Background

The early detection of muscle loss in patients with chronic kidney disease (CKD) is crucial. The creatinine muscle index (CMI, mg/day/1.73 m²), which is calculated as the product of serum creatinine, is easily available in daily care and estimates the muscle mass. However, the association between CMI and muscle mass has not been fully assessed. We aimed to investigate whether CMI can serve as a predictor of muscle mass in patients with CKD.

Methods

This cross-sectional study included patients with CKD undergoing kidney biopsy and plain computed tomography (CT) to assess the kidney morphology. Muscle mass was assessed using the psoas muscle index, determined by dividing the cross-sectional psoas muscle area at the L3 level, measured by manual tracing on pre-biopsy CT, by the participant's height (cm²/m²).

Results

In total, 159 participants (84 male [52.8%], mean age 51.7 ± 16 years) were included. CMI was positively correlated with PMI in men (r = 0.37, p < 0.01) and women (r = 0.56, p < 0.01). The prevalence of low muscle mass was 55 (65.5%) in men and 44 (58.7%) in women. The odds ratios (ORs) and 95% confidence intervals (CIs) for low muscle mass were significantly higher in Tertile 1 of CMI than in Tertile 3 in both men and women (OR, 5.37 [95% CI, 1.32–21.8] in men; OR, 7.31 [95% CI, 1.38–38.6] in women) after adjusting for age, body mass index and co-morbidities (hypertension and diabetes). According to receiver operating characteristics curves, the optimal cut-off value of CMI for low muscle mass was 1079 mg/day/1.73 m² (area under the curve 0.69 [95% CI: 0.57–0.81]; sensitivity, 0.78; specificity, 0.62) in men and 693 mg/day/1.73 m² (area under the curve 0.74 [95%CI: 0.63–0.85]; sensitivity, 0.57; specificity, 0.90) in women.

Conclusions

CMI is significantly associated with muscle mass in patients with CKD. Our findings suggest the utility of CMI for screening the muscle mass in this population.

背景慢性肾脏疾病（CKD）患者肌肉损失的早期检测至关重要。肌酸酐肌指数（CMI, mg/day/1.73 m2）是血清肌酐的乘积，在日常护理中很容易获得，可以估计肌肉质量。然而，CMI与肌肉质量之间的关系尚未得到充分评估。我们的目的是研究CMI是否可以作为CKD患者肌肉质量的预测因子。方法本横断面研究纳入CKD患者进行肾脏活检和计算机断层扫描（CT）以评估肾脏形态。通过腰大肌指数评估肌肉质量，腰大肌指数由腰大肌在L3水平的横断面面积除以参与者的身高（cm2/m2）确定，通过活检前CT手工追踪测量。结果共纳入159例，其中男性84例，占52.8%，平均年龄51.7±16岁。男性CMI与PMI呈正相关（r = 0.37, p < 0.01），女性CMI与PMI呈正相关（r = 0.56, p < 0.01）。低肌肉量的患病率男性为55(65.5%)，女性为44（58.7%）。男性和女性中，第1梯级患者低肌肉质量的比值比（OR）和95%可信区间（CI）均显著高于第3梯级患者(男性OR为5.37 [95% CI, 1.32-21.8]；在调整了年龄、体重指数和合并症（高血压和糖尿病）后，OR为7.31 [95% CI, 1.38-38.6]（女性）。根据受试者工作特征曲线，低肌量CMI的最佳临界值为1079 mg/day/1.73 m2(曲线下面积0.69 [95% CI: 0.57-0.81]；敏感性,0.78;特异性为0.62)，男性为693 mg/天/1.73 m2(曲线下面积0.74 [95%CI: 0.63-0.85]；敏感性,0.57;女性特异性为0.90)。结论慢性肾病患者CMI与肌肉质量显著相关。我们的研究结果表明CMI在筛查这一人群的肌肉质量方面的效用。

{"title":"Creatinine Muscle Index as a Novel Muscle Mass Indicator in Patients With Chronic Kidney Disease","authors":"Hiroki Nobayashi, Go Kanzaki, Aoi Okubo, Nobuo Tsuboi, Takashi Yokoo","doi":"10.1002/rco2.116","DOIUrl":"https://doi.org/10.1002/rco2.116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The early detection of muscle loss in patients with chronic kidney disease (CKD) is crucial. The creatinine muscle index (CMI, mg/day/1.73 m<sup>2</sup>), which is calculated as the product of serum creatinine, is easily available in daily care and estimates the muscle mass. However, the association between CMI and muscle mass has not been fully assessed. We aimed to investigate whether CMI can serve as a predictor of muscle mass in patients with CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study included patients with CKD undergoing kidney biopsy and plain computed tomography (CT) to assess the kidney morphology. Muscle mass was assessed using the psoas muscle index, determined by dividing the cross-sectional psoas muscle area at the L3 level, measured by manual tracing on pre-biopsy CT, by the participant's height (cm<sup>2</sup>/m<sup>2</sup>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 159 participants (84 male [52.8%], mean age 51.7 ± 16 years) were included. CMI was positively correlated with PMI in men (<i>r</i> = 0.37, <i>p</i> < 0.01) and women (<i>r</i> = 0.56, <i>p</i> < 0.01). The prevalence of low muscle mass was 55 (65.5%) in men and 44 (58.7%) in women. The odds ratios (ORs) and 95% confidence intervals (CIs) for low muscle mass were significantly higher in Tertile 1 of CMI than in Tertile 3 in both men and women (OR, 5.37 [95% CI, 1.32–21.8] in men; OR, 7.31 [95% CI, 1.38–38.6] in women) after adjusting for age, body mass index and co-morbidities (hypertension and diabetes). According to receiver operating characteristics curves, the optimal cut-off value of CMI for low muscle mass was 1079 mg/day/1.73 m<sup>2</sup> (area under the curve 0.69 [95% CI: 0.57–0.81]; sensitivity, 0.78; specificity, 0.62) in men and 693 mg/day/1.73 m<sup>2</sup> (area under the curve 0.74 [95%CI: 0.63–0.85]; sensitivity, 0.57; specificity, 0.90) in women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CMI is significantly associated with muscle mass in patients with CKD. Our findings suggest the utility of CMI for screening the muscle mass in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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