Impact of waitlist weight change on outcomes in heart transplant recipients: a UNOS database analysis.

BACKGROUND: While the effect of pre-transplant weight on patient outcomes following heart transplantation (HTx) has previously been studied, data regarding the impact of dynamic weight change prior to HTx are extremely limited. OBJECTIVES: We sought to elucidate the interaction between HTx listing weight and weight change while waitlisted, and explore how that interaction impacts post-HTx survival in a continuous manner. METHODS: Adult patients listed for HTx from 1987 to 2020 were identified from UNOS database. Three-dimensional restricted cubic spline analysis explored post-HTx survival relative to both changes in BMI/weight and BMI at time of HTx listing. Continuous predictor variables were analyzed with Cox proportional hazards method. RESULTS: 9,628 included patients underwent HTx. Median recipient age was 55 [IQR 46-62] years, and 21% were females. 53% of patients lost while 47% gained weight on the waitlist. Median BMI (27.6 kg/m2 [24.3-31.3] vs. 27.4 kg/m2 [24.2-30.9], paired p < 0.001) and weight (84.8 kg [73.0-98.0] kg vs. 84.4 kg [72.6-96.6], p < 0.001) were similar at listing and transplant. One-year survival was 89.3%. Weight loss over 3 BMI points or 10 kg was associated with higher hazard of death irrespective of listing BMI. In non-obese patients, some weight gain (1-4 BMI points or 5-15 kg) was associated with improved survival. In cachectic patients (BMI < 18.5), failure to gain weight was associated with worse survival. CONCLUSIONS: Impact of weight change varies depending on listing BMI. While a survival benefit is seen in non-obese patients who gain some weight, significant weight loss is associated with poorer survival.

Cachexia in tuberculosis in South-East Asian and African regions: knowledge gaps and untapped opportunities.

Tuberculosis (TB) and cachexia are clinical entities that have a defined relationship, making them often found together. TB can lead to cachexia, while cachexia is a risk factor for TB. This article reviews cachexia in Tuberculosis patients in Southeast Asian and African regions by conducting a comprehensive literature search across electronic databases such as PubMed, Google Scholar, and Research Gate between 2013 and 2024 using keywords including 'Africa', 'cachexia', 'prevalence', 'implications', 'tuberculosis', and 'Southeast Asia. This article utilized only studies that satisfied the inclusion criteria, revealing knowledge gaps and untapped opportunities for cachexia in TB across Southeast Asian and African regions. Many Southeast Asian and Western Pacific patients initially receive a tuberculosis diagnosis. Sub-Saharan African countries are among the 30 high TB burden nations, according to the WHO. Food inadequacy and heightened energy expenditure can impair the immune system, leading to latent TB and subsequently, active infection. Symptoms needing attention: shortness of breath, productive cough, hyponatremia at 131 mmol/l, hypoalbuminemia at 2.1 g/dl, elevated aspartate transaminase at 75 U/l, increased lactate dehydrogenase at 654, and normocytic anemia. Comorbidities, such as kidney disease, cardiovascular disease, and asthma, can influence the nutritional status of individuals with TB. While efforts like screening, contact tracing, and utilizing gene Xpert to detect TB cases were implemented, only a few proved effective. It is essential to conduct further studies, including RCTs, in Southeast Asia and Africa to evaluate and manage cachexia in TB patients.

Relationship between Survival Days, Cancer Cachexia, and Activities of Daily Living in Palliative Cancer Patients Undergoing Rehabilitation.

Objectives: Cancer cachexia has many effects on physical function and causes a decline in activities of daily living (ADL). Therefore, rehabilitation programs should be structured according to the degree of cancer cachexia. Currently, the evaluation of cancer cachexia is mainly based on body mass. However, there is no report on the use of the modified Glasgow Prognostic Score (mGPS) to evaluate the degree of cancer cachexia and survival prognosis in palliative cancer patients for whom rehabilitation has been prescribed. This study used mGPS to examine the prevalence of cancer cachexia in palliative cancer patients undergoing rehabilitation and the impacts of cancer cachexia, ADL, and complications on survival. Methods: The participants included 135 palliative cancer patients who were admitted to the hospital and underwent rehabilitation between 2020 and 2022. Cancer cachexia classification by mGPS was conducted, and logistic regression analysis was used to examine factors affecting the survival of palliative cancer patients undergoing rehabilitation. Results: The patients were grouped as follows: 6 (4.4%) normal, 13 (9.6%) undernourished, 12 (9.0%) pre-cachexia, and 104 (77.0%) refractory cachexia. Logistic regression analysis showed that the mGPS and BI affected survival. Conclusions: In a cohort of palliative cancer patients undergoing rehabilitation, 86% had cachexia. mGPS and BI were associated with survival outcomes. Combination of mGPS classification with ADL assessment may provide meaningful prognostic information in these patients.

Impact of Cachexia and First-Line Systemic Therapy for Previously Untreated Advanced Non-Small Cell Lung Cancer: NEJ050A.

BACKGROUND: Cancer cachexia complicates advanced non-small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first-line systemic therapy. METHODS: We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first-line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first-line systemic therapy. RESULTS: A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0-2 who were initiated on first-line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first-line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy-associated emesis affecting early appetite-related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: -3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (-1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression-free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003). CONCLUSIONS: Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite-related QOL trends vary based on the type of first-line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter.

Leptin as a surrogate immune-metabolic marker to predict impact of anti-cachectic therapy: results of a prospective randomized trial in multiple solid tumors.

DESCRIPTION OF THE WORK: Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia. PURPOSE: To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment. PATIENTS AND METHODS: From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life. RESULTS: A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue. CONCLUSIONS: Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs.

Withaferin A ameliorates ovarian cancer-induced renal damage through the regulation of expression of inflammatory cytokines.

BACKGROUND: Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage. METHODS: We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -800C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1ß, IL-6, TNF-α, TGF-ß, GDF-15, and MYD88). RESULTS: Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 ß (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice. CONCLUSIONS: Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer.

Fu-Zheng-Li-Fei Recipe (FZLFR) in the treatment of Cancer Cachexia: Exploration of the Efficacy and Molecular Mechanism Based on Chemical characterization, Experimental Research and Network Pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: FZLFR was derived from a classic traditional Chinese medicine recipe, the Shiquan-Dabu decoction. FZLFR is commonly used in clinical practice to address muscle loss and associated cancer cachexia. However, the mechanism of by which FZLFR acts in cancer cachexia remains unclear. AIM: This study aimed to assess the effects and explore the potential mechanism of action of FZLFR in treating cancer cachexia. METHODS: Cancer cachexia was induced by inoculating Lewis lung carcinoma cells into the right flank of male C57BL/6 mice. The efficacy of FZLFR was evaluated by comparing changes in body weight, tumor mass, food intake, survival time, weight, and cross-sectional area of the gastrocnemius and anterior tibial muscles. Moreover, inflammatory cytokines, such as TNF-α and IL-6, were detected by ELISA. The chemical components of FZLFR were analyzed using ultra-performance liquid chromatography-coupled with time-of-flight mass spectrometry. Network pharmacology analysis was performed to screen the core targets and potential pathways involved in FZLFR treatment of cancer cachexia. Molecular docking was used to analyze the binding ability of the core targets and key compounds. The expression levels of core targets and targets correlated with skeletal muscle atrophy were also assessed using western blotting. RESULTS: FZLFR enhanced the food intake and survival rate of mice with cancer cachexia. It also alleviated tumor-induced body weight loss, tumor growth, and muscle fiber atrophy in these mice. Additionally, it improved the weight and cross-sectional area of the gastrocnemius and anterior tibial muscles. FZLFR down-regulated the serum levels of TNF-α and IL-6. UPLC-ESI-Q-TOF-MS analysis identified 184 compounds in FZLFR. Network pharmacology analysis predicted that TNF signaling pathway, ErbB signaling pathway and VEGF signaling pathway might be essential in FZLFR action. Molecular docking showed that kaempferol, upafolin, apigenin, and luteolin might play key roles in FZLFR treatment. Moreover, FZLFR decreased MAFBx1, MURF1, NF-κB, TWEAK, MAPK8, and EGFR expression levels. FZLFR enhanced the expression of VEGFA and ESR1, as demonstrated by western blotting. CONCLUSIONS: FZLFR increased food intake and alleviated muscle atrophy in mice with cancer cachexia. The potential pharmacological mechanisms underlying its anticachexia effects include reducing inflammation, enhancing muscle vascular growth, inhibiting tumor angiogenesis, and modulating estrogen receptors.

Cancer knocks you out by fasting: Cachexia as a consequence of metabolic alterations in cancer.

Neoplastic transformation reprograms tumor and surrounding host cell metabolism, increasing nutrient consumption and depletion in the tumor microenvironment. Tumors uptake nutrients from neighboring normal tissues or the bloodstream to meet energy and anabolic demands. Tumor-induced chronic inflammation, a high-energy process, also consumes nutrients to sustain its dysfunctional activities. These tumor-related metabolic and physiological changes, including chronic inflammation, negatively impact systemic metabolism and physiology. Furthermore, the adverse effects of antitumor therapy and tumor obstruction impair the endocrine, neural, and gastrointestinal systems, thereby confounding the systemic status of patients. These alterations result in decreased appetite, impaired nutrient absorption, inflammation, and shift from anabolic to catabolic metabolism. Consequently, cancer patients often suffer from malnutrition, which worsens prognosis and increases susceptibility to secondary adverse events. This review explores how neoplastic transformation affects tumor and microenvironment metabolism and inflammation, leading to poor prognosis, and discusses potential strategies and clinical interventions to improve patient outcomes.

The additional benefit of computed tomography in cancer patients: impacts of sarcopenia and cachexia on quality of life during chemotherapy.

Objective: This study evaluates the effects of sarcopenia and cachexia on the quality of life (QoL) of patients with gastrointestinal cancer during their initial cycle of chemotherapy, emphasizing the significance of computed tomography (CT) in assessing muscle mass. Materials and Methods: In this prospective study, we evaluated 60 adult patients with gastrointestinal cancer who started chemotherapy between January and December of 2017. Sarcopenia was diagnosed on the basis of CT findings, and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Results: The mean age was 60.9 years, and 33 (55.0%) of the patients were men. Of the 60 patients, 33 (55.0%) had cachexia and 14 (23.3%) had sarcopenia. Chemotherapy significantly reduced QoL, particularly in the physical, role functioning, and social domains, with no differences between the cachexia and sarcopenia groups. Conclusion: Among patients with gastrointestinal cancer submitted to chemotherapy, the chemotherapy-induced decline in QoL does not seem to differ significantly between those with cachexia or sarcopenia, as classified by CT-measured muscle mass, and those without. However, CT-based muscle mass evaluation remains crucial for guiding customized intervention strategies. Integrating this evaluation in radiological reports can provide valuable insights for planning specific care, thus improving patient QoL during treatment.

Objetivo: Este estudo avalia os efeitos da sarcopenia e da caquexia na qualidade de vida de pacientes com câncer gastrointestinal durante o ciclo inicial de quimioterapia, enfatizando a importância da tomografia computadorizada (TC) na avaliação da massa muscular. Materiais e Métodos: Estudo prospectivo com 60 pacientes adultos com câncer gastrointestinal que iniciaram quimioterapia de janeiro a dezembro de 2017. A TC foi utilizada para o diagnóstico de sarcopenia e o Quality of Life Questionnaire Core 30 da European Organization for Research and Treatment of Cancer foi utilizado para avaliar a qualidade de vida. Resultados: A média de idade dos pacientes foi 60,9 anos e 33 (55%) eram homens. Entre os pacientes, 33 (55%) eram caquéticos e 14 (24%) eram sarcopênicos. A quimioterapia reduziu significativamente a qualidade de vida, especialmente nos domínios físico, de desempenho de papéis e social, sem diferenças entre os grupos caquéticos e sarcopênicos. Conclusão: A diminuição da qualidade de vida não difere significativamente entre pacientes caquéticos/sarcopênicos e não caquéticos/não sarcopênicos com câncer gastrointestinal submetidos a quimioterapia, conforme classificado pela massa muscular medida por TC. No entanto, a avaliação da massa muscular por TC continua crucial para orientar estratégias de intervenção personalizadas. A integração dessa avaliação nos laudos radiológicos pode fornecer informações valiosas para o planejamento de cuidados específicos, melhorando a qualidade de vida dos pacientes durante o tratamento.

The Prevalence and Prognosis of Cachexia in Patients with Non-Sarcopenic Dysphagia: A Retrospective Cohort Study.

The purpose of this study was to assess the prevalence and prognosis of cachexia in patients with non-sarcopenic dysphagia. A retrospective cohort study was conducted using the Japanese sarcopenic dysphagia database. Cachexia was diagnosed using the Asian Working Group for Cachexia criteria, sarcopenia using the Asian Working Group for Sarcopenia 2019 criteria, and malnutrition using the Global Leadership Initiative on Malnutrition criteria. Outcomes were death, swallowing function (Food Intake LEVEL Scale (FILS)), and activities of daily living (Barthel Index (BI)). The mean age of the 175 non-sarcopenic dysphagia patients was 77 (±11) years; 103 (59%) were male, 30 (17%) had cachexia, 133 (76%) had whole-body sarcopenia, and 92 (53%) were malnourished. Of the 30 patients with cachexia, 4 and 11 did not have sarcopenia and malnutrition, respectively. No significant associations were found between cachexia, sarcopenia, and malnutrition. Death was notably higher in the cachexia group (5/30; 17% vs. 2/145; 1%, p = 0.002). Median FILS (7 vs. 8, p = 0.585) and median BI (35 vs. 50, p = 0.469) scores did not show significant differences based on cachexia status. The prevalence of cachexia was 17%, and mortality may be higher with cachexia in non-sarcopenic dysphagia patients.

Salivary Interleukin-13 and Transforming Growth Factor Beta as Potential Biomarkers of Cancer Cachexia.

Cancer cachexia is a syndrome characterized by weight and muscle loss and functional impairment, strongly influencing survival in cancer patients. In this study, we aimed to establish the role of saliva cytokine measurement in cancer cachexia investigation and define two potential independent salivary biomarkers of the condition. METHODS: serum and saliva specimens were obtained from 78 patients. Forty-six patients were non-cachectic, and 32 patients were cachectic (per SCRINIO group criteria), all with metastatic solid tumors. Commercial ELISA kits were used to determine the salivary and serum concentrations of interleukin 13 (IL-13) and transforming growth factor beta (TGF-ß) in two patient groups and healthy controls. Laboratory values were obtained from the hospital information system, and weight and height were measured at the time of sampling. RESULTS: A statistically significant difference was observed between the groups in saliva IL-13 concentrations but no difference in serum concentrations. Statistically significant differences were also observed between the groups in saliva and serum concentrations of TGF-ß. Logistic regression analysis has identified salivary IL-13 and TGF-ß as independent factors for cancer cachexia. CONCLUSIONS: We demonstrated saliva as a valuable specimen for cachexia investigation and established IL-13 and TGF-ß as potential cancer cachexia biomarkers. Further research is needed to evaluate these findings.

Transdermal Fentanyl in Patients with Cachexia-A Scoping Review.

Cachectic patients frequently require transdermal fentanyl (TDF) for pain management, but data on its efficacy and safety are scarce and inconsistent. This scoping review aims to analyze the evidence concerning TDF administration in patients with cachexia irrespective of the underlying pathology. The primary objective is to assess the analgesic efficacy and tolerability of TDF in cachectic patients. The secondary objective is to identify cachexia characteristics that may influence fentanyl pharmacokinetics (PK). A comprehensive search of PubMed, Embase, and Web of Science databases was conducted up to March 2024. The review included observational and clinical studies on cachectic patients with moderate to severe pain treated with TDF patches at any dosage or frequency. Phase 1 trials, animal studies, case reports, preclinical studies and conference abstracts were excluded. Nine studies were included: four studies reported that cachexia negatively impacted TDF efficacy, increasing required doses and lowering plasma concentrations; three studies found minimal or no impact of cachexia on TDF efficacy and PK; two studies suggested that cachexia might improve TDF outcomes. Study quality ranged from moderate to high, according to the National Institutes of Health (NIH) Quality Assessment Tool. The current evidence is insufficient to provide any definitive recommendations for TDF prescribing in cachectic patients.

Supplementation with Fish Oil and Selenium Protects Lipolytic and Thermogenic Depletion of Adipose in Cachectic Mice Treated with an EGFR Inhibitor.

Lung cancer and cachexia are the leading causes of cancer-related deaths worldwide. Cachexia is manifested by weight loss and white adipose tissue (WAT) atrophy. Limited nutritional supplements are conducive to lung cancer patients, whereas the underlying mechanisms are poorly understood. In this study, we used a murine cancer cachexia model to investigate the effects of a nutritional formula (NuF) rich in fish oil and selenium yeast as an adjuvant to enhance the drug efficacy of an EGFR inhibitor (Tarceva). In contrast to the healthy control, tumor-bearing mice exhibited severe cachexia symptoms, including tissue wasting, hypoalbuminemia, and a lower food efficiency ratio. Experimentally, Tarceva reduced pEGFR and HIF-1α expression. NuF decreased the expression of pEGFR and HIF-2α, suggesting that Tarceva and NuF act differently in prohibiting tumor growth and subsequent metastasis. NuF blocked LLC tumor-induced PTHrP and expression of thermogenic factor UCP1 and lipolytic enzymes (ATGL and HSL) in WAT. NuF attenuated tumor progression, inhibited PTHrP-induced adipose tissue browning, and maintained adipose tissue integrity by modulating heat shock protein (HSP) 72. Added together, Tarceva in synergy with NuF favorably improves cancer cachexia as well as drug efficacy.

Machine learning to identify precachexia and cachexia: a multicenter, retrospective cohort study.

BACKGROUND: Detection of precachexia is important for the prevention and treatment of cachexia. However, how to identify precachexia is still a challenge. OBJECTIVE: This study aimed to detect cancer precachexia using a simple method and distinguish the different characteristics of precachexia and cachexia. METHODS: We included 3896 participants in this study. We used all baseline characteristics as input variables and trained machine learning (ML) models to calculate the importance of the variables. After filtering the variables based on their importance, the models were retrained. The best model was selected based on the receiver operating characteristic value. Subsequently, we used the same method and process to identify patients with precachexia in a noncachexia population using the same method and process. RESULTS: Participants in this study included 2228 men (57.2%) and 1668 women (42.8%), of whom 471 were diagnosed with precachexia, 1178 with cachexia, and the remainder with noncachexia. The most important characteristics of cachexia were eating changes, arm circumference, high-density lipoprotein (HDL) level, and C-reactive protein albumin ratio (CAR). The most important features distinguishing precachexia were eating changes, serum creatinine, HDL, handgrip strength, and CAR. The two logistic regression models for screening for cachexia and diagnosing precachexia had the highest area under the curve values of 0.830 and 0.701, respectively. Calibration and decision curves showed that the models had good accuracy. CONCLUSION: We developed two models for identifying precachexia and cachexia, which will help clinicians detect and diagnose precachexia.

Immunomodulation: A new approach to cancer cachexia, potentially suitable for aging.

Cancer cachexia is the prototypical example of comorbidity, occurring in most of cancer patients. It is a direct consequence of tumor growth and of the associated inflammatory/immune response. Cachexia can be exacerbated by anti-cancer therapies, frequently resulting in dose limitation and/or treatment delay or discontinuation. The pathogenesis of cancer cachexia is still unclear and includes nutritional, metabolic, hormonal and immunological components. Tumor ability to shape the immune response to its own advantage is now well accepted, while the possibility that such an altered immune response could play a role in the onset of cachexia is still an undefined issue. Indeed, most of the immune-related research on cachexia mainly focused on pro-inflammatory mediators, almost totally disregarding the interactions among immune cells and the homeostasis of peripheral tissues. The present review provides an overview of the immune system dysregulations occurring in cancer cachexia, focusing on the possibility that immunomodulating strategies, mainly developed to stimulate the anti-cancer immune response, could be useful to counteract cachexia as well. Cancer and cachexia are frequent comorbidities of aging. Along this line, cancer- and aging-associated muscle wasting likely coexist in the same patients. Since both conditions share some of the underlying mechanisms, the potential effectiveness of immunomodulation on sarcopenia of aging is discussed.

[The frequency of cachexia and its associated factors in elderly diabetic patients with chronic diseases: A study using the diagnostic criteria of the Asian Working Group for Cachexia].

OBJECTIVE: To evaluate the frequency of cachexia and its associated factors using the Asian Working Group for Cachexia (AWGC) criteria in elderly patients with diabetes and chronic diseases. METHODS: The subjects were diabetic outpatients of ≥65 years of age who were managed at Ise Red Cross Hospital. Patients with chronic disease (chronic heart failure, cancer, or chronic renal failure). Cachexia was evaluated based on the AWGC criteria and was defined as a body mass index (BMI) <21 kg/m2 and one or more of the following: anorexia, elevated C-reactive protein, and decreased grip strength. A logistic regression analysis was used to identify cachexia-related factors, with cachexia as the dependent variable, and various variables (basic attributes, blood glucose-related parameters, diabetic complications, comorbidities, and treatment) as explanatory variables. RESULTS: Two hundred forty-two patients (male, n=164; female, n=78) were included in the study. Forty patients (16.5%) had cachexia. A logistic analysis revealed that age (odds ratio (OR), 1.16; P<0.001), type 1 diabetes (OR, 15.25; P=0.002), diabetic retinopathy (OR, 5.72; P=0.001), and physical frailty (OR, 7.06; P<0.001) were associated with cachexia. CONCLUSION: Elderly diabetics with chronic diseases were more likely to have cachexia. According to the AWGC criteria, the frequency of cachexia was 16.5% in elderly patients with diabetes and chronic diseases. Additionally, type 1 diabetes, diabetic retinopathy, age, and physical frailty were identified as factors associated with cachexia. In elderly diabetes patients with chronic diseases, it is therefore important to raise awareness regarding cachexia when these related factors are diagnosed.

Traditional Chinese Medicine Monomers Are Potential Candidate Drugs for Cancer-Induced Cardiac Cachexia.

BACKGROUND: Cardiovascular diseases are now the second leading cause of death among cancer patients. Heart injury in patients with terminal cancer can lead to significant deterioration of left ventricular morphology and function. This specific heart condition is known as cancer-induced cardiac cachexia (CICC) and is characterized by cardiac dysfunction and wasting. However, an effective pharmacological treatment for CICC remains elusive. SUMMARY: The development and progression of CICC are closely related to pathophysiological processes, such as protein degradation, oxidative responses, and inflammation. Traditional Chinese medicine (TCM) monomers offer unique advantages in reversing heart injury, which is the end-stage manifestation of CICC except the regular treatment. This review outlines significant findings related to the impact of eleven TCM monomers, namely Astragaloside IV, Ginsenosides Rb1, Notoginsenoside R1, Salidroside, Tanshinone II A, Astragalus polysaccharides, Salvianolate, Salvianolic acids A and B, and Ginkgolide A and B, on improving heart injury. These TCM monomers are potential therapeutic agents for CICC, each with specific mechanisms that could potentially reverse the pathological processes associated with CICC. Advanced drug delivery strategies, such as nano-delivery systems and exosome-delivery systems, are discussed as targeted administration options for the therapy of CICC. KEY MESSAGE: This review summarizes the pathological mechanisms of CICC and explores the pharmacological treatment of TCM monomers that promote anti-inflammation, antioxidation, and pro-survival. It also considers pharmaceutical strategies for administering TCM monomers, highlighting their potential as therapies for CICC.

A comprehensive review of animal models for cancer cachexia: Implications for translational research.

Cancer cachexia is a multifactorial syndrome characterized by progressive weight loss and a disease process that nutritional support cannot reverse. Although progress has been made in preclinical research, there is still a long way to go in translating research findings into clinical practice. One of the main reasons for this is that existing preclinical models do not fully replicate the conditions seen in clinical patients. Therefore, it is important to understand the characteristics of existing preclinical models of cancer cachexia and pay close attention to the latest developments in preclinical models. The main models of cancer cachexia used in current research are allogeneic and xenograft models, genetically engineered mouse models, chemotherapy drug-induced models, Chinese medicine spleen deficiency models, zebrafish and Drosophila models, and cellular models. This review aims to revisit and summarize the commonly used animal models of cancer cachexia by evaluating existing preclinical models, to provide tools and support for translational medicine research.

The prognostic impact of perioperative dynamic changes in cachexia index in patients with hepatocellular carcinoma.

Background: The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been associated with prognosis in patients with hepatocellular carcinoma (HCC). We hypothesized that dynamic changes in CXI might be associated with long-term outcomes in HCC. Methods: This study comprised 131 patients who had undergone primary hepatic resection for HCC between 2008 and 2019. Preoperative CXI (pre-CXI) and postoperative CXI (post-CXI) were calculated by the following formula: skeletal muscle index x serum albumin level / neutrophil-to-lymphocyte ratio. Pre- and post-CXI were classified into two groups (high vs. low). We retrospectively investigated the association of perioperative dynamic changes in CXI with disease-free and overall survival. Results: In multivariate analyses, negative HBs-antigen (p = 0.02), high serum PIVKA-II level (p < 0.01), poor tumor differentiation (p = 0.02), multiple tumors (p < 0.01), microvascular invasion (p < 0.01), partial resection (p < 0.01), postoperative complications (p < 0.01), and low-pre-CXI (p < 0.01) were significant predictors of disease-free survival, while high ICGR15 (p = 0.01), poor tumor differentiation (p < 0.01), multiple tumors (p = 0.01), postoperative complications (p < 0.01), low-pre-CXI (p < 0.01), and low-post-CXI (p < 0.01) were significant predictors of overall survival. Low-post-CXI was associated with older age (p = 0.045), larger tumor (p < 0.01), longer operation time (p = 0.047), greater intraoperative bleeding (p < 0.01), and intraoperative blood transfusion (p < 0.01). Moreover, dynamic changes in CXI were associated with overall survival in each subgroup of patients with low-pre-CXI (p = 0.02) or high-pre-CXI (p = 0.03). Conclusions: Not only post-CXI but also dynamic changes in CXI from pre- to post-hepatectomy can be a prognostic indicator of HCC, providing a compelling rationale for aggressive perioperative nutritional and physical interventions to improve long-term outcomes.

Increased Myocardial MAO-A, Atrogin-1, and IL-1ß Expression in Transgenic Mice with Pancreatic Carcinoma-Benefit of MAO-A Inhibition for Cardiac Cachexia.

Cancer cachexia (CC) continues to challenge clinicians by massively impairing patients' prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac cachexia as characterized by atrophy, compromised metabolism, innervation and function of the myocardium through factors awaiting clarification for therapeutic targeting. Because monoamine oxidase-A (MAO-A) is a myocardial source of H2O2 and implicated in myofibrillar protein catabolism and heart failure, we presently studied myocardial MAO-A expression, inflammatory cells, and capillarization together with transcripts of pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic signals (by qRT-PCR) in a 3x-transgenic (LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre) mouse model of orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) mice. Moreover, we evaluated the effect of MAO-A inhibition by application of harmine hydrochloride (HH, 8 weeks, i.p., no sham control) on PDAC-related myocardial alterations. Myocardial MAO-A protein content was significantly increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with an increased percentage of atrogin-1+ (p < 0.001), IL-1ß+ (p < 0.01), COX2+ (p < 0.001), and CD68+ (p > 0.05) cells and enhanced transcripts of pro-inflammatory IL-1ß (2.47-fold), COX2 (1.53-fold), TNF (1.87-fold), and SOCS3 (1.64-fold). Moreover, PDAC was associated with a reduction in capillary density (-17%, p < 0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3. Importantly, HH treatment largely reversed the PDAC-related increases in atrogin-1+, IL-1ß+, and TNF+ cell fraction as well as in COX2, IL-1ß, TNF, and SOCS3 transcripts, whereas capillary density and KDR transcripts failed to improve. In mice with PDAC, increased myocardial pro-atrophic/-inflammatory signals are attributable to increased expression of MAO-A, because they are significantly improved with MAO-A inhibition as a potential novel therapeutic option. The PDAC-related loss in myocardial capillary density may be due to other mechanisms awaiting evaluation with consideration of cardiomyocyte size, cardiac function and physical activity.