Sarcopenia,Malnutrition, and Cachexia: Adapting Definitions and Terminology of Nutritional Disorders in Older People with Cancer

The recent publication of the revised Consensus on definition and diagnosis of sarcopenia (EWGSOP2) and the Global Leadership Initiative on Malnutrition (GLIM) criteria changed the approach to research on sarcopenia and malnutrition. Whilst sarcopenia is a nutrition-related disease, malnutrition and cachexia are nutritional disorders sharing the common feature of low fat-free mass. However, they have differential characteristics and etiologies, as well as specific therapeutic approaches. Applying the current definitions in clinical practice is still a challenge for health professionals and the potential for misdiagnosis is high. This is of special concern in the subgroup of older people with cancer, in which sarcopenia, malnutrition, and cancer cachexia are highly prevalent and can overlap or occur separately. The purpose of this review is to provide an updated overview of the latest research and consensus definitions of sarcopenia, malnutrition, and cachexia and to discuss their implications for clinical practice in older patients with cancer. The overall aim is to improve the quality of nutritional care in light of the latest findings.     

Dietary Supplements in People with Metastatic Cancer Who Are Experiencing Malnutrition,Cachexia, Sarcopenia,and Frailty: A Scoping Review

Cancer-associated malnutrition, or cachexia, stemming from cancer or its treatments, is particularly prevalent in metastatic cancers, and is often interrelated with sarcopenia and frailty. Evidence suggests that dietary supplements play a role in managing these conditions. As metastatic cancer cells are associated with notable genomic and phenotypic alterations, response to dietary supplements may differ between metastatic and non-metastatic cancers. However, research in this area is lacking. This scoping review aims to identify the dietary supplements that have been studied in patients with metastatic cancers and malnutrition-related conditions, along with their proposed effects, mechanisms, outcome measures, and tools used. A systematic search was conducted across databases, including MEDLINE, EMBASE, CINAHL, and clinical trial registries. Of the initial 6535 records screened, a total of 48 studies were included, covering a range of dietary supplements—vitamins, minerals, antioxidants, proteins, amino acids, fatty acids, fiber, and others. While the types of dietary supplements included varied across cancer types, omega-3 and carnitine were investigated most often. Proposed relevant attributes of dietary supplements included their antioxidant, anti-inflammatory, anti-cancer, and immunomodulatory properties. Overall, there was a paucity of interventional studies, and more randomized controlled trials are warranted.     

Clinical Implications of Malnutrition in the Management of Patients with Pancreatic Cancer: Introducing the Concept of the Nutritional Oncology Board

Pancreatic cancer represents a very challenging disease, with an increasing incidence and an extremely poor prognosis. Peculiar features of this tumor entity are represented by pancreatic exocrine insufficiency and an early and intense nutritional imbalance, leading to the highly prevalent and multifactorial syndrome known as cancer cachexia. Recently, also the concept of sarcopenic obesity has emerged, making the concept of pancreatic cancer malnutrition even more multifaceted and complex. Overall, these nutritional derangements play a pivotal role in contributing to the dismal course of this malignancy. However, their relevance is often underrated and their assessment is rarely applied in clinical daily practice with relevant negative impact for patients’ outcome in neoadjuvant, surgical, and metastatic settings. The proper detection and management of pancreatic cancer-related malnutrition syndromes are of primary importance and deserve a specific and multidisciplinary (clinical nutrition, oncology, etc.) approach to improve survival, but also the quality of life. In this context, the introduction of a “Nutritional Oncology Board” in routine daily practice, aimed at assessing an early systematic screening of patients and at implementing nutritional support from the time of disease diagnosis onward seems to be the right path to take.     

Prevalence and Associated Factors of Coexistence of Malnutrition and Sarcopenia in Geriatric Rehabilitation

Malnutrition and sarcopenia often coexist in rehabilitation patients, although they are often overlooked and undertreated in clinical practice. This cross-sectional study aimed to clarify the prevalence of the coexistence of malnutrition and sarcopenia (Co-MS) and its associated factors in convalescent rehabilitation wards in Japan. Consecutive patients aged ≥ 65 years in convalescent rehabilitation wards between November 2018 and October 2020 were included. Malnutrition and sarcopenia were determined by the Global Leadership Initiative on Malnutrition (GLIM) criteria and the Asian Working Group for Sarcopenia (AWGS 2019) criteria, respectively. Patients who presented both with malnutrition and sarcopenia were classified as Co-MS. Potentially associated factors included age, sex, days from onset to admission of rehabilitation wards, reason for admission, pre-morbid functional dependency, comorbidity, activities of daily living, swallowing ability, and oral function and hygiene. The prevalence of malnutrition, sarcopenia, and Co-MS was calculated. Binary logistic regression analyses were performed to compute odds ratios (ORs) and the 95% confidence interval (CI) of possible associated factors for each condition. Overall, 601 patients were eligible for the analysis (median 80 years old, 355 female patients, 70% cerebrovascular disease). Co-MS, malnutrition, and sarcopenia were found in 23.5%, 29.0%, and 62.4% of the enrolled patients, respectively. After adjustment, onset–admission interval (OR = 1.04; 95% CI = 1.02 to 1.06), hospital-associated deconditioning (OR = 4.62; 95% CI = 1.13 to 18.8), and swallowing ability (Food Intake LEVEL Scale) (OR = 0.83; 95% CI = 0.73 to 0.93) were identified as independent explanatory factors of Co-MS. In conclusion, Co-MS was prevalent in geriatric rehabilitation patients; thus, healthcare professionals should be aware of the associated factors to detect the geriatric rehabilitation patients who are at risk of both malnutrition and sarcopenia, and to provide appropriate treatments.     

A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.     

Polypharmacy and Malnutrition Management of Elderly Perioperative Patients with Cancer: A Systematic Review

Malnutrition, which commonly occurs in perioperative patients with cancer, leads to decreased muscle mass, hypoalbuminemia, and edema, thereby increasing the patient’s risk of various complications. Thus, the nutritional management of perioperative patients with cancer should be focused on to ensure that surgical treatment is safe and effective, postoperative complications are prevented, and mortality is reduced. Pathophysiological and drug-induced factors in elderly patients with cancer are associated with the risk of developing malnutrition. Pathophysiological factors include the effects of tumors, cachexia, and anorexia of aging. Metabolic changes, such as inflammation, excess catabolism, and anabolic resistance in patients with tumor-induced cancer alter the body’s ability to use essential nutrients. Drug-induced factors include the side effects of anticancer drugs and polypharmacy. Drug–drug, drug–disease, drug–nutrient, and drug–food interactions can significantly affect the patient’s nutritional status. Furthermore, malnutrition may affect pharmacokinetics and pharmacodynamics, potentiate drug effects, and cause side effects. This review outlines polypharmacy and malnutrition, the impact of malnutrition on drug efficacy, drug–nutrient and drug–food interactions, and intervention effects on polypharmacy or cancer cachexia in elderly perioperative patients with cancer.     

Malnutrition According to GLIM Criteria and Adverse Outcomes in Community-Dwelling Chinese Older Adults: A Prospective Analysis

ObjectivesThe Global Leadership Initiative on Malnutrition (GLIM) has proposed a consensus scheme for classifying malnutrition. This study examined the prevalence of malnutrition according to GLIM criteria and evaluated if these criteria were associated with adverse outcomes in community-dwelling older adults.DesignThis was a prospective cohort study.Setting and ParticipantsCommunity-dwelling Chinese men and women aged ≥65 years in Hong Kong.MethodsA health check including questionnaire interviews and physical measurements was conducted at baseline and 14-year follow-up. Participants were classified as malnourished at baseline according to the GLIM criteria based on 2 phenotypic components (low body mass index and reduced muscle mass) and 1 etiologic component (inflammation). Adverse outcomes including sarcopenia, frailty, falls, mobility limitation, hospitalization, and mortality were assessed at 14-year follow-up. Adjusted multiple logistic regression and Cox proportional hazards model were performed to examine the associations between malnutrition and adverse outcomes and presented as odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI).ResultsData of 3702 participants [median age: 72 years (IQR 68–76)] were available at baseline. Malnutrition was present in 397 participants (10.7%). Malnutrition was significantly associated with higher risk of sarcopenia (n = 898, OR 2.25; 95% CI 1.04–4.86), frailty (Fried (n = 971, OR 2.83; 95% CI 1.47–5.43), FRAIL scale (n = 985, OR 2.30; 95% CI 1.06–4.98)) and all-cause mortality (n = 3702, HR: 1.62; 95% CI 1.39–1.89). There was no significant association between malnutrition and falls (n = 987, OR 1.09; 95% CI 0.52–2.31), mobility limitation (n = 989, OR 0.98; 95% CI 0.36–2.67), and hospitalization (n = 989, OR 1.37; 95% CI 0.67–2.77).Conclusions and ImplicationsAmong community-dwelling Chinese older adults, malnutrition according to selected GLIM criteria was a predictor of sarcopenia, frailty, and mortality at 14-year follow-up; whereas no association was found for falls, mobility limitation, and hospitalization. Clinicians may consider applying the GLIM criteria to identify malnourished community-dwelling older adults.     

Pancreatic Cancer Prognosis,Malnutrition Risk,and Quality of Life: A Cross-Sectional Study

The present cross-sectional prospective study (from January 2017 until December 2020) aimed to evaluate the interrelation between nutritional parameters at the initial evaluation with the changes in QOL indicators and the Progression-Free Survival and Overall Survival in 97 patients with pancreatic cancer. Dietary and nutritional risk assessments, and an evaluation of Frailty and Functional Status were performed. Health-related Quality of Life was evaluated with the EORTC QLQ-C30 questionnaire. Nutritional risk, as evaluated by MNA-SF score, was negatively associated with age (p = 0.003) and positively associated with dynamometry (p = 0.001). In addition, there was a statistically significant difference in the financial difficulties (p = 0.049). OS and PFS were found to decrease in patients who reported having increased fatigue (OS p = 0.007 and PFS p = 0.044). Moreover, higher prevalence of constipation resulted in lower OS and PFS (OS p < 0.001 and PFS p < 0.001) and increased reporting of gastrointestinal problems during the 3 months was connected with lower survival (OS p = 0.017). According to the analysis, our patients were found to have lower OS and PFS, stressing out the necessity to provide early identification and management to symptoms of the disease that could compromise nutritional status. The provision of nutritional advice and guidance is of major importance for patients.     

Nutritional Approach to Cancer Cachexia: A Proposal for Dietitians

Cachexia is one of the most common, related factors of malnutrition in cancer patients. Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass and fat mass, resulting in irreversible and progressive functional impairment. The skeletal muscle loss cannot be reversed by conventional nutritional support, and a combination of anti-inflammatory agents and other nutrients is recommended. In this review, we reviewed the effects of nutrients that are expected to combat muscle loss caused by cancer cachexia (eicosapentaenoic acid, β-hydroxy-β-methylbutyrate, creatine, and carnitine) to propose nutritional approaches that can be taken at present. Current evidence is based on the intake of nutrients as supplements; however, the long-term and continuous intake of nutrients as food has the potential to be useful for the body. Therefore, in addition to conventional nutritional support, we believe that it is important for the dietitian to work with the clinical team to first fully assess the patient’s condition and then to safely incorporate nutrients that are expected to have specific functions for cancer cachexia from foods and supplements.     

Disease-Related Malnutrition and Sarcopenia Predict Worse Outcome in Medical Inpatients: A Cohort Study

(1) Background: Both sarcopenia and disease-related malnutrition (DRM) are unfortunately underdiagnosed and undertreated in our Western hospitals, which could lead to worse clinical outcomes. Our objectives included to determine the impact of low muscle mass (MM) and strength, and also DRM and sarcopenia, on clinical outcomes (length of stay, death, readmissions at three months, and quality of life). (2) Methodology: Prospective cohort study in medical inpatients. On admission, MM and hand grip strength (HGS) were assessed. The Global Leadership Initiative on Malnutrition (GLIM) criteria were used to diagnose DRM and EWGSOP2 for sarcopenia. Assessment was repeated after one week and at discharge. Quality of life (EuroQoL-5D), length of stay (LoS), readmissions and mortality are reported. (3) Results: Two hundred medical inpatients, median 76.0 years-old and 68% with high comorbidity. 27.5% met GLIM criteria and 33% sarcopenia on admission, increasing to 38.1% and 52.3% on discharge. Both DRM and sarcopenia were associated with worse QoL. 6.5% died and 32% readmission in 3 months. The odds ratio (OR) of mortality for DRM was 4.36 and for sarcopenia 8.16. Readmissions were significantly associated with sarcopenia (OR = 2.25) but not with DRM. A higher HGS, but not MM, was related to better QoL, less readmissions (OR = 0.947) and lower mortality (OR = 0.848) after adjusting for age, sex, and comorbidity. (4) Conclusions: In medical inpatients, mostly polymorbid, both DRM but specially sarcopenia are associated with poorer quality of life, more readmissions, and higher mortality. Low HGS proved to be a stronger predictor of worse outcomes than MM.     

Differential Diagnosis of Cachexia and Refractory Cachexia and the Impact of Appropriate Nutritional Intervention for Cachexia on Survival in Terminal Cancer Patients

Cancer cachexia subsequently shifts to refractory cachexia, however, it is not easy to properly differentiate them in clinical settings. Patients considered refractory cachexia may include cachectic patients with starvation. This study aimed to identify these cachectic patients and to evaluate the effect of nutritional intervention for them. Study subjects were terminal cancer patients admitted for palliative care and were judged refractory cachexia in the last five years. We retrospectively examined to find useful indices for identifying such cachectic patients and for evaluating the effect of nutritional intervention. Out of 223 patients in refractory cachexia, 26 were diagnosed cachexia with starvation after symptom management. Comparing before and one week after this management, Palliative Performance Scale (PPS) and transthyretin significantly improved (p < 0.0001, p = 0.0002, respectively) Then, we started nutritional intervention for these cachectic patients and divided into effective group (n = 17) and non-effective group (n = 9) using the criteria for cachexia. Comparing between the two groups, PPS significantly improved2 weeks after intervention in effective group (p = 0.006). Survival time was significantly longer in effective group (p = 0.008). PPS and transthyretin were useful for differential diagnosis of cachexia and refractory cachexia. PPS was useful for evaluating nutritional intervention for cachectic patients. Appropriate nutritional intervention improved survival.     

Defining and Classifying Cancer Cachexia: A Proposal by the SCRINIO Working Group

Background: Although cancer cachexia is widely diffuse in the cancer patient population, there is no objective definition and classification of this syndrome. The purpose of this study is to propose a simple and quick classification that relies on the severity of the body weight loss and presence/absence of symptoms that are associated with cancer cachexia. Methods: The authors used a database of an ongoing multicenter prospective investigation on the screening of the nutrition risk of 1307 cancer outpatients from different (mainly Italian) university or scientific institutes or hospitals. The database included demographic, oncologic, clinical, and nutrition data. The patients were divided into 4 classes based on combinations of body weight loss (<10%, precachexia; ≥10%, cachexia) and the presence/absence of at least 1 symptom of anorexia, fatigue, or early satiation. The authors verified statistically whether these 4 classes were associated with the distribution of main clinical, nutrition, and oncologic variables, after adjustment for treatment status, by using the Cochrane‐Mantel‐Hanszel test for count data and ANOVA for continuous data. Results: Moving from “asymptomatic precachexia” (class 1) to “symptomatic cachexia” (class 4), there were statistically significant trends (P < .0001) in the percentage of gastrointestinal vs nongastrointestinal tumors, severity of cancer stage, percentage of weight loss, number of symptoms per patient, Eastern Cooperative Oncology Group (ECOG) performance status, and nutritional risk score. Conclusions: The statistical analysis has validated the classification by identifying stages with different severity of cachexia. This classification could be adopted within a comprehensive oncologic approach to the weight‐losing patients, until more specific diagnostic techniques are available in clinical practice.     

Sarcopenic Dysphagia,Malnutrition, and Oral Frailty in Elderly: A Comprehensive Review

Frailty is a highly prevalent condition in the elderly that has been increasingly considered as a crucial public health issue, due to the strict correlation with a higher risk of fragility fractures, hospitalization, and mortality. Among the age-related diseases, sarcopenia and dysphagia are two common pathological conditions in frail older people and could coexist leading to dehydration and malnutrition in these subjects. “Sarcopenic dysphagia” is a complex condition characterized by deglutition impairment due to the loss of mass and strength of swallowing muscles and might be also related to poor oral health status. Moreover, the aging process is strictly related to poor oral health status due to direct impairment of the immune system and wound healing and physical and cognitive impairment might indirectly influence older people’s ability to carry out adequate oral hygiene. Therefore, poor oral health might affect nutrient intake, leading to malnutrition and, consequently, to frailty. In this scenario, sarcopenia, dysphagia, and oral health are closely linked sharing common pathophysiological pathways, disabling sequelae, and frailty. Thus, the aim of the present comprehensive review is to describe the correlation among sarcopenic dysphagia, malnutrition, and oral frailty, characterizing their phenotypically overlapping features, to propose a comprehensive and effective management of elderly frail subjects.     

CT-Determined Sarcopenia in GLIM-Defined Malnutrition and Prediction of 6-Month Mortality in Cancer Inpatients

Our objective was to evaluate the clinical application of third lumbar vertebra (L3)-computer tomography (CT)-determined sarcopenia as a marker of muscle mass in cancer inpatients diagnosed with malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and to establish its association with 6-month mortality. Methods: This was an observational, prospective study in patients from an inpatient oncology unit. We performed a nutritional assessment according to GLIM criteria, including muscle cross-sectional area at L3 by CT and skeletal muscle index (SMI). Six-month mortality was evaluated. Results: A total of 208 patients were included. The skeletal muscle cross-sectional area at L3 was 136.2 ± 32.5 cm² in men and 98.1 ± 21.2 cm² in women. The SMI was 47.4 ± 12.3 cm²/m² in men and 38.7 ± 8.3 cm²/m² in women. Sarcopenia (low SMI) was detected in 59.6% of the subjects. Using SMI as a marker of low muscle mass in application of GLIM criteria, we found 183 (87.9%) malnourished patients. There were 104 deaths (50%) at 6 months. The deceased patients had a lower skeletal muscle cross-sectional area (112.9 ± 27.9 vs. 126.1 ± 37.8 cm²; p = 0.003) and a lower SMI (41.3 ± 9.5 vs. 45.7 ± 12.9 cm²/m²; p = 0.006). An increased risk of 6-month mortality was found in malnourished patients according to GLIM criteria using SMI (HR 2.47; 95% confidence interval 1.07–5.68; p = 0.033). Conclusions: Low muscle mass, assessed by L3-CT, was observed to affect more than half of cancer inpatients. The deceased patients at 6 months had a lower skeletal muscle cross-sectional area and SMI. Malnutrition according to GLIM criteria using CT-determined sarcopenia was shown to adequately predict 6-month mortality.     

Malnutrition in Older Adults—Effect on Falls and Fractures: A Narrative Review

Malnutrition in older adults impacts health status, increased mortality, and morbidity. Malnutrition may increase the development of geriatric syndromes and contribute to a higher prevalence of falls and osteoporotic fractures that lead to loss of independence and an increased rate of institutionalization. The role of malnutrition in the pathogenesis of other geriatric syndromes seems to be well established. However, the data concerning nutritional interventions are confounding. Moreover, long-term undernutrition seems to be one of the factors that strongly influences the efficacy of interventions. This review outlines the current literature on this topic, and aims to guide physicians to make proper decisions to prevent the vicious cycle of falls, fractures, and their negative outcomes in patients with malnutrition.     

Frailty,Sarcopenia, and Malnutrition Frequently (Co-)occur in Hospitalized Older Adults: A Systematic Review and Meta-analysis

ObjectivesThe purpose of this systematic review and meta-analysis was to summarize the prevalence of, and association between, physical frailty or sarcopenia and malnutrition in older hospitalized adults.DesignA systematic literature search was performed in 10 databases.Setting and ParticipantsArticles were selected that evaluated physical frailty or sarcopenia and malnutrition according to predefined criteria and cutoffs in older hospitalized patients.MeasuresData were pooled in a meta-analysis to evaluate the prevalence of prefrailty and frailty [together (pre-)frailty], sarcopenia, and risk of malnutrition and malnutrition [together (risk of) malnutrition], and the association between either (pre-)frailty or sarcopenia and (risk of) malnutrition.ResultsForty-seven articles with 18,039 patients (55% female) were included in the systematic review, and 39 articles (8868 patients, 62% female) were eligible for the meta-analysis. Pooling 11 studies (2725 patients) revealed that 84% [95% confidence interval (CI): 77%, 91%, I² = 98.4%] of patients were physically (pre-)frail. Pooling 15 studies (4014 patients) revealed that 37% (95% CI: 26%, 48%, I² = 98.6%) of patients had sarcopenia. Pooling 28 studies (7256 patients) revealed a prevalence of 66% (95% CI: 58%, 73%, I² = 98.6%) (risk of) malnutrition. Pooling 10 studies (2427 patients) revealed a high association [odds ratio (OR): 5.77 (95% CI: 3.88, 8.58), P < .0001, I² = 42.3%] and considerable overlap (49.7%) between physical (pre-)frailty and (risk of) malnutrition. Pooling 7 studies (2506 patients) revealed a high association [OR: 4.06 (95% CI: 2.43, 6.80), P < .0001, I² = 71.4%] and considerable overlap (41.6%) between sarcopenia and (risk of) malnutrition.Conclusions and ImplicationsThe association between and prevalence of (pre-)frailty or sarcopenia and (risk of) malnutrition in older hospitalized adults is substantial. About half of the hospitalized older adults suffer from 2 and perhaps 3 of these debilitating conditions. Therefore, standardized screening for these conditions at hospital admission is highly warranted to guide targeted nutritional and physical interventions.     

Long Term Follow-Up of Sarcopenia and Malnutrition after Hospitalization for COVID-19 in Conventional or Intensive Care Units

Background: The post-COVID-19 condition, defined as COVID-19-related signs and symptoms lasting at least 2 months and persisting more than 3 months after infection, appears now as a public health issue in terms of frequency and quality of life alterations. Nevertheless, few data are available concerning long term evolution of malnutrition and sarcopenia, which deserve further attention. Method: Sarcopenia was investigated prospectively, together with weight evolution, at admission and at 3 and 6 months after hospital discharge in 139 COVID-19 patients, using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, associating both decreased muscle strength and muscle mass, assessed, respectively, with hand dynamometer and dual-energy X-ray absorptiometry. Results: Of the 139 patients, 22 presented with sarcopenia at 3 months; intensive care units (ICU) length of stay was the sole factor associated with sarcopenia after multivariate analysis. Although the entire group did not demonstrate significant weight change, weight decreased significantly in the sarcopenia group (Five and eight patients, showing, respectively, >5 or >10% weight decrease). Interestingly, at 6 months, 16 of the 22 patients recovered from sarcopenia and their weight returned toward baseline values. Conclusions: Sarcopenia and malnutrition are frequently observed in patients hospitalized for COVID-19, even 3 months after infection occurrence, but can largely be reversed at 6 months after discharge. Enhanced patient care is needed in sarcopenic patients, particularly during long stays in an ICU.