Novel therapeutic options for cachexia and sarcopenia

ABSTRACT

Introduction: Cachexia and sarcopenia are conditions phenotypically characterized by muscle loss and represent a factor of poor prognosis, increasing patients’ morbidity and mortality. Cachectic and sarcopenic patients often suffer from low quality of life, presenting lower muscle strength and appetite loss, which makes research on novel treatment strategies to ameliorate clinical response including patient’s symptoms, the objective of scientific interest.

Areas covered: This article covers recent developments in the area of cachexia and sarcopenia treatment and therapeutic interventions, targeting central nervous system involvement, key inflammatory and muscle-specific metabolic pathways.

Expert opinion: A number of promising agents have being evaluated, such as enobosarm, a selected androgen receptor modulator, and anamorelin, a ghrelin agonist which have been recently studied in phase III trials. These and other agents (i.e., infliximab, tocilizumab, MABp1, bimagrumab) have shown significant impact on reversal of skeletal muscle loss, but limited effect on physical function.

In the last few years advancement in the number and type of potential treatments for cachexia and sarcopenia have been obtained and we have now available more data on measurable effects of several drugs on patients’ nutritional and metabolic parameters and outcomes.     

血清VIP水平与老年人群骨密度及肌肉减少症相关性研究

目的探索血管活性肠肽(vasoactive intestinal peptide,VIP)水平与老年人群骨密度和肌肉减少症相关性。方法受试者包括216名成年人(79名男性和137名女性;平均年龄73.5岁)接受全面体检。检测所有受试者骨骼肌指数(SMI)、腰椎(L1-L4)和股骨颈骨密度和步行速度,符合亚洲肌肉减少症工作组标准的受试者被分配到肌肉减少症组。仅肌肉量减少的受试者被分配到肌量减少组,其他受试者分配到正常组。Oswestry功能障碍指数(ODI)和腰痛视觉模拟评分(VAS)用于评估腰痛。同时检测血清VIP水平;对三组之间肌肉减少症决定因素如骨密度、VAS和VIP等数据进行统计学分析。结果12名受试者(5.5%)患有肌肉减少症。肌肉减少症组的平均ODI评分显著高于肌量减少组和正常组[分别为(25.2±12.3)%、(11.2±10.0)%和(11.9±12.3)%,P<0.05]。肌肉减少症组血清VIP水平显著低于肌量减少组和正常组(P<0.05)。肌肉减少症组的腰椎(L1-L4)和股骨颈骨密度和BMI显著低于其他组(P<0.05)。腰椎(L1-L4)和股骨颈骨密度及步行速度、ODI与血清VIP水平之间存在正相关(P<0.05)。结论老年人群中肌肉减少症及腰椎(L1-L4)和股骨颈骨密度、腰痛与血清VIP水平密切相关。     

Implications of low muscle mass across the continuum of care: a narrative review

Abstract

Abnormalities in body composition can occur at any body weight. Low muscle mass is a predictor of poor morbidity and mortality and occurs in several populations. This narrative review provides an overview of the importance of low muscle mass on health outcomes for patients in inpatient, outpatient and long-term care clinical settings. A one-year glimpse at publications that showcases the rapidly growing research of body composition in clinical settings is included. Low muscle mass is associated with outcomes such as higher surgical and post-operative complications, longer length of hospital stay, lower physical function, poorer quality of life and shorter survival. As such, the potential clinical benefits of preventing and reversing this condition are likely to impact patient outcomes and resource utilization/health care costs. Clinically viable tools to measure body composition are needed for routine screening and intervention. Future research studies should elucidate the effectiveness of multimodal interventions to counteract low muscle mass for optimal patient outcomes across the healthcare continuum.

• Key messages

• Low muscle mass is associated with several negative outcomes across the healthcare continuum.

• Techniques to identify and counteract low muscle mass in clinical settings are needed.

     

铁死亡相关肌肉骨骼系统疾病的概述及中医药干预进展

铁死亡是一种新型的细胞死亡形式,与铁过载和脂质过氧化有关,在许多疾病的发展中具有重要作用。骨质疏松症、骨关节炎、类风湿关节炎、骨肉瘤、脊髓损伤、肌少症等肌肉骨骼系统疾病严重影响患者生活质量,已成为全球公共卫生系统的主要负担。铁死亡与上述肌肉骨骼系统疾病的发生发展密切相关,表明铁死亡可能成为肌肉骨骼系统疾病的治疗的新靶点。中医药在肌肉骨骼系统疾病治疗中有其独特的优势,已有大量研究证实中医药通过铁死亡途径参与肌肉骨骼系统疾病的调节,显示出良好的研究前景。通过探讨铁死亡与肌肉骨骼系统疾病的关联,总结中医药通过介导铁死亡防治肌肉骨骼系统疾病研究进展,为开发新的治疗策略及中医药更好的治疗肌肉骨骼系统疾病治疗提供思路。     

Binge-eating disorder is associated with an unfavorable body mass composition in patients with non-alcoholic fatty liver disease

The interaction between eating disorders and non-alcoholic fatty liver disease (NAFLD) remains unexplored, especially with regards to binge-eating disorder (BED). Our team conducted a service evaluation project in order to assess risk factors for the presence of BED among patients with NAFLD and the impact of BED on body mass composition. The overall prevalence of patients screening positive to BED Screener-7 (BEDS-7) was 28.4%, while a previous diagnosis of depression and marital status (as single or separated) were independently associated with positive BED. Furthermore, patients with positive BEDS-7 had higher BMI, with greater visceral component and overall lower muscle mass. There was no difference in terms of liver disease severity as assessed by noninvasive markers of fibrosis. However, as body mass composition and sarcopenia have been shown to be associated to disease progression in patients with NAFLD, further studies are required to ascertain the long-term impact of BED in these patients. Moreover, further work is warranted to identify to implement multidisciplinary approach within clinical psychology for the management of patients with BED, who may be particularly challenging in terms of achieving lifestyle modifications. As a hepatology community, we should address NAFLD with a more holistic approach.     

中国八城市老年人能量及蛋白质摄入与肌肉衰减症的关系

目的探究中国八城市老年人能量、蛋白质摄入水平与肌肉衰减症的关系。方法数据来源于2016年的"中国城市成年人群膳食与健康关系研究"。采用立意抽样和多阶段整群抽样相结合的方法,抽取65岁及以上研究对象427人,采用问卷调查的方法获得社会人口学特征和生活习惯,采用24小时膳食回顾调查法获得调查对象膳食摄入情况并根据《中国食物成分表》计算能量、蛋白质摄入。使用四分位数将研究对象按照能量摄入水平分为4组:Q1(<1197.6 kcal/d)、Q2(1197.6~1531.4 kacl/d)、Q3(1531.4~1984.1 kcal/d)、Q4(≥1984.1 kacl/d);使用四分位数将研究对象按照蛋白质摄入水平分为4组:Q1(<36.8 g/d)、Q2(36.8~50.4 g/d)、Q3(50.4~68.6 g/d)、Q4(≥68.6 g/d)。生物电阻抗法测量四肢骨骼肌质量,使用手持握力计测量骨骼肌力量,四米步速测试测量骨骼肌功能。根据亚洲肌肉衰减症工作组的标准评价调查人群的骨骼肌健康现状。结果与Q1组相比,能量摄入水平较高的Q2~Q4组的四肢骨骼肌质量、握力、步速以及肌肉衰减症检出率差异无统计学意义。与Q1组相比,蛋白质摄入Q2组具有较大的握力(β=0.12,95%CI 0.03~0.21,P=0.009)和较快的步速(β=0.20,95%CI 0.07~0.34,P=0.003)。结论膳食蛋白质摄入水平与中国老年人握力及步速存在关联,但与肌肉衰减症检出率无显著关联。     

L-Glutamine Supplementation Enhances Strength and Power of Knee Muscles and Improves Glycemia Control and Plasma Redox Balance in Exercising Elderly Women

We investigated the effects of oral L-glutamine (Gln) supplementation, associated or not with physical exercises, in control of glycemia, oxidative stress, and strength/power of knee muscles in elderly women. Physically active (n = 21) and sedentary (n = 23) elderly women aged 60 to 80 years were enrolled in the study. Plasma levels of D-fructosamine, insulin, reduced (GSH) and oxidized (GSSG) glutathione, iron, uric acid, and thiobarbituric acid-reactive substances (TBARs) (lipoperoxidation product), as well as knee extensor/flexor muscle torque peak and average power (isokinetic test), were assessed pre- and post-supplementation with Gln or placebo (30 days). Higher plasma D-fructosamine, insulin, and iron levels, and lower strength/power of knee muscles were found pre-supplementation in the NPE group than in the PE group. Post-supplementation, Gln subgroups showed higher levels of GSH, GSSG, and torque peak, besides lower D-fructosamine than pre-supplementation values. Higher muscle average power and plasma uric acid levels were reported in the PE + Gln group, whereas lower insulin levels were found in the NPE + Gln than pre-supplementation values. TBARs levels were diminished post-supplementation in all groups. Gln supplementation, mainly when associated with physical exercises, improves strength and power of knee muscles and glycemia control, besides boosting plasma antioxidant capacity of elderly women.     

The Spectrum of Malnutrition/Cachexia/Sarcopenia in Oncology According to Different Cancer Types and Settings: A Narrative Review

Nutritional status in oncological patients may differ according to several modifiable and non-modifiable factors. Knowledge of the epidemiology of malnutrition/cachexia/sarcopenia may help to manage these complications early in the course of treatment, potentially impacting patient quality of life, treatment intensity, and disease outcome. Therefore, this narrative review aimed to critically evaluate the current evidence on the combined impact of tumor- and treatment-related factors on nutritional status and to draw some practical conclusions to support the multidisciplinary management of malnutrition in cancer patients. A comprehensive literature search was performed from January 2010 to December 2020 using different combinations of pertinent keywords and a critical evaluation of retrieved literature papers was conducted. The results show that the prevalence of weight loss and associated symptoms is quite heterogeneous and needs to be assessed with recognized criteria, thus allowing a clear classification and standardization of therapeutic interventions. There is a large range of variability influenced by age and social factors, comorbidities, and setting of cures (community-dwelling versus hospitalized patients). Tumor subsite is one of the major determinants of malnutrition, with pancreatic, esophageal, and other gastroenteric cancers, head and neck, and lung cancers having the highest prevalence. The advanced stage is also linked to a higher risk of developing malnutrition, as an expression of the relationship between tumor burden, inflammatory status, reduced caloric intake, and malabsorption. Finally, treatment type influences the risk of nutritional issues, both for locoregional approaches (surgery and radiotherapy) and for systemic treatment. Interestingly, personalized approaches based on the selection of the most predictive malnutrition definitions for postoperative complications according to cancer type and knowledge of specific nutritional problems associated with some new agents may positively impact disease course. Sharing common knowledge between oncologists and nutritionists may help to better address and treat malnutrition in this population.