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Cancer-related anorexia-cachexia syndrome (CACS) is a debilitating condition afflicting up to 80% of advanced-stage cancer patients. Characterized by progressive weight loss, muscle wasting, and metabolic abnormalities, CACS significantly compromises patients' quality of life and treatment outcomes. This comprehensive review navigates through its intricate physiopathology, elucidating its stages and diagnostic methodologies. CACS manifests in three distinct stages: pre-cachexia, established cachexia, and refractory cachexia. Early detection is pivotal for effective intervention and is facilitated by screening tools, complemented by nutritional assessments and professional evaluations. The diagnostic process unravels the complex interplay of metabolic dysregulation and tumor-induced factors contributing to CACS. Management strategies, tailored to individual patient profiles, encompass a spectrum of nutritional interventions. These include dietary counseling, oral nutritional supplements, and, when necessary, enteral nutrition and a judicious use of parenteral nutrition. Specific recommendations for caloric intake, protein requirements, and essential nutrients address the unique challenges posed by CACS. While pharmacological agents like megestrol acetate may be considered, their use requires careful evaluation of potential risks. At its core, this review underscores the imperative for a holistic and personalized approach to managing CACS, integrating nutritional interventions and pharmacological strategies based on a nuanced understanding of patient's condition. [ABSTRACT FROM AUTHOR]

Background: It was reported that the cachexia index (CXI: ALB * SMI NLR ) was an essential index for predicting the prognosis of tumor patients. However, since for SMI needs to be measured by CT imaging methods and its calculation was inconvenient. Thus, we developed a modified cachexia index (mCXI: ALB NLR * UCR ). The purpose of this study was to evaluate the association between mCXI and prognosis in patients with colorectal cancer. Methods: An analysis of 215 patients with newly diagnosed colorectal cancer was carried out retrospectively. An optimal cut-off value of mCXI was established by the receiver operating characteristic (ROC) curves for predicting prognosis. Prognostic implications of mCXI were investigated using Kaplan–Meier curves and Cox regression analysis. A comparative assessment of the predictive capacity between mCXI and the CXI was performed using time-dependent receiver operating characteristic analysis. Results: Patients were classified into two groups based on the cut-off value of mCXI: the LOW mCXI group (n = 60) and the HIGH mCXI group (n = 155). The 3-year Overall survival (OS) (76.6% vs 96.7%, p < 0.01) and 3-year Recurrence-free survival (RFS) (68.3% vs 94.1%, p < 0.01) were significantly worse in the LOW mCXI group in contrast to that in the HIGH mCXI group. In Cox multivariate regression analysis, mCXI was an independent prognostic factor for OS (HR = 8.951, 95%CI: 3.105–25.807, <0.01). Moreover, compared with CXI (AUC = 0.723), mCXI (AUC = 0.801) has better predictive efficacy, indicating that mCXI is more suitable for prognostic assessment. Conclusions: The mCXI significantly correlated with survival outcomes for colorectal cancer patients after radical surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Immunonutrition (IN) is defined as using special nutritional substrates (immnonutrients) to regulate the nutritional status as well as immune and inflammatory functions. Patients with cancer often have chronic inflammation and impaired immune function due to the disease and its treatment, affecting the quality of life of patients and the outcome of cancer treatment. Malnutrition, metabolic abnormalities, immune imbalances and inflammatory responses permeate the entire process of tumor development and progression. Therefore, IN has its great potential in the treatment of cancer patients. Although there has been a large body of evidence, the application of IN in cancer patients meets the challenge, such as the optimal administration time, application population, ingredients of IN, and the dosage and ratio of application etc. Besides, new studies with better designed are emerging. The aim of this review is to summarize recent evidences in IN in patients with cancer, and to guide the clinical application. [ABSTRACT FROM AUTHOR]

Most patients with advanced cancer develop cachexia, a multifactorial syndrome characterized by progressive skeletal muscle wasting. Despite its catastrophic impact on survival, the critical mediators responsible for cancer cachexia development remain poorly defined. Here, we show that a distinct subset of neutrophil-like monocytes, which we term cachexia-inducible monocytes (CiMs), emerges in the advanced cancer milieu and promotes skeletal muscle loss. Unbiased transcriptome analysis reveals that interleukin 36 gamma (IL36G)-producing CD38+ CiMs are induced in chronic monocytic blood cancer characterized by prominent cachexia. Notably, the emergence of CiMs and the activation of CiM-related gene signatures in monocytes are confirmed in various advanced solid cancers. Stimuli of toll-like receptor 4 signaling are responsible for the induction of CiMs. Genetic inhibition of IL36G-mediated signaling attenuates skeletal muscle loss and rescues cachexia phenotypes in advanced cancer models. These findings indicate that the IL36G-producing subset of neutrophil-like monocytes could be a potential therapeutic target in cancer cachexia. The critical mediators responsible for cancer-associated cachexia development remain poorly defined. Here, the authors identify a distinct subset of neutrophil-like monocytes that facilitates progressive skeletal muscle wasting in cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Heart failure (HF) can cause metabolic imbalances, leading to anabolic resistance and increased energy expenditure, which often results in weight loss and cachexia. Comprehensive cardiac rehabilitation (CR), including exercise, nutritional support, and risk management, is crucial for enhancing the health and quality of life of patients with HF and is expected to play a central role in the prevention and treatment of HF-associated cachexia. However, the prevalence of cachexia in patients with HF undergoing comprehensive outpatient CR is currently unknown, and the detailed characteristics including of motor function of such patients remain undefined. Therefore, this cross-sectional study aimed to investigate the prevalence and characteristics of cachexia and the relationship between cachexia and lower limb motor function in patients with HF undergoing outpatient CR. This study included 115 consecutive patients with HF (43% male; mean age, 78 ± 8 years) who underwent comprehensive outpatient CR. The cachexia status was assessed according to the definition proposed by the Asian Working Group on Cachexia in 2023. The Short Physical Performance Battery (SPPB) and Mini Nutritional Assessment Short-Form (MNA-SF) were used to evaluate motor function of the lower limbs and nutritional status, respectively. Multivariate logistic regression analyses were used to examine the potential relationship between cachexia and low SPPB scores (≤ 9 points). The prevalence of cachexia was 30% in this study. Compared with those without cachexia, patients with cachexia were significantly older and showed notable reductions in body mass index, MNA-SF scores, handgrip strength, gait speed, and SPPB scores. A multivariate logistic regression analysis, adjusted for confounders, revealed that both age (odds ratio [OR], 1.129; 95% confidence interval [CI], 1.034–1.248; P = 0.016) and presence of cachexia (OR, 3.783; 95% CI, 1.213–11.796; P = 0.022) were independently associated with low SPPB scores. These findings highlight the importance of focusing on cachexia in patients with HF as part of a comprehensive outpatient CR and may be crucial in developing treatments to improve lower limb motor function in patients with HF who develops cachexia. [ABSTRACT FROM AUTHOR]

Both cancer and cardiovascular disease (CVD) cause skeletal muscle mass loss, thereby increasing the likelihood of a poor prognosis. We investigated the association between cancer history and physical function and their combined association with prognosis in patients with CVD. We retrospectively reviewed 3,796 patients with CVD (median age: 70 years; interquartile range [IQR]: 61–77 years) who had undergone physical function tests (gait speed and 6-minute walk distance [6MWD]) at discharge. We performed multiple linear regression analyses to assess potential associations between cancer history and physical function. Moreover, Kaplan–Meier curves and Cox regression analyses were used to evaluate prognostic associations in four groups of patients categorized by the absence or presence of cancer history and of high or low physical function. Multiple regression analyses showed that cancer history was significantly and independently associated with a lower gait speed and 6MWD performance. A total of 610 deaths occurred during the follow-up period (median: 3.1 years; IQR: 1.4–5.4 years). The coexistence of low physical function and cancer history in patients with CVD was associated with a significantly higher mortality risk, even after adjusting for covariates (cancer history/low gait speed, hazard ratio [HR]: 1.93, P < 0.001; and cancer history/low 6MWD, HR: 1.61, P = 0.002). Cancer history is associated with low physical function in patients with CVD, and the combination of both factors is associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is a common malignancy that affects adults worldwide, causing a high disease burden. Few studies have examined the relationship between body composition (BC) measures and the prevalence of CRC. Our purpose was to investigate the relationship between pertinent BC indicators and CRC. Methods: Bioelectrical impedance analysis, laboratory test results, face-to-face questionnaire investigation, and nutritional risk assessment (Nutritional Risk Screening 2002 and Patient-Generated Subjective Global Assessment) were used in this case-control study. Bioelectrical impedance analysis in the case group was performed prior to antitumor therapy/surgery. Results: From June 2018 to January 2019, a total of 303 cases and 286 controls were included. The results showed that low body fat percentage (BFP) and high visceral adiposity index (VAI) groups had a higher risk of developing CRC in comparison to the normal BFP and normal VAI groups. The risk of CRC decreased with the increase of BFP. The group with a normal BC had a lower risk of developing CRC compared to those with a greater VAI and a lower BFP, as indicated by the results of the pairwise and total combinations of VAI, fat-free mass index (FFMI), and BFP. Additionally, FFMI and VAI had positive correlations with prealbumin, serum albumin, and nutritional risk scores. Conclusion: Low BFP and high VAI are associated with higher CRC risk. FFMI and VAI are positively correlated with prealbumin, serum albumin, and nutritional risk scores in CRC patients. [ABSTRACT FROM AUTHOR]

A model for accelerated aging in mice was developed: CB6F2 mice aged 39-45 days were exposed to fractionated 4-fold relatively uniform γ-radiation (137Cs, 0.98 Gy/min) at a total dose of 6.8 Gy. Radiation exposure led to delayed active growth, leukopenia, and lymphopenia for over 1 year during the post-radiation period. The death of irradiated males and females occurred significantly earlier than in control group animals. Median lifespans in the experimental group were 35-38% lower than in the control group (p<0.001). Ionizing radiation exposure led to the early development of hair depigmentation, cachexia, and the development of aging-associated diseases. In irradiated mice, oncological pathology constituted 30-35% in the mortality structure, which is twice as often as in the control group. The developed model can be used to study the pathogenesis of accelerated aging under radiation exposure and the search for means of its prevention and treatment. [ABSTRACT FROM AUTHOR]

Purpose of Review: The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. Recent Findings: Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Summary: Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence. [ABSTRACT FROM AUTHOR]

Purpose: Quality of life (QoL), appetite, cachexia, and biomarkers [albumin, hemoglobin (Hb), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), interleukin 8 (IL-8), C-X-C motif chemokine ligand 5 (CXCL5) and citrullinated histoneH3 (H3Cit)] were compared for 40 cases with advanced cancer and 40 healthy controls. Baseline differences and significant relationships were explored for biomarkers with QoL, appetite, and cachexia. Methods: In a prospective case–control, age and sex matched study, the European Organisation for the Research and Treatment of Cancer Quality of Life–C30 questionnaire (EORTC-QLQ-C30) for QoL, the Functional Assessment of Anorexia and Cachexia Therapy assessment (FAACT A/CS-12) for appetite, and a five-factor cachexia assessment tool for cachexia assessment were performed. Routine hematological measurements and blood chemistry analyses together with ELISA procedures and a Multiplex® bead array platform, were used for biomarker analysis. Descriptive statistics and regression analyses were undertaken. P < 0.05 defined statistical significance. Results: Global health status (QL-G), functional scales (QL-FS), and symptom scales (QL-SS) differed for cases and controls (p < 0.01). In cases, differences were observed for QL-G (p < 0.01), QL-FS (p < 0.01), and QL-SS (p = 0.01) compared to standardized references values. FAACT A/CS-12 scores differed significantly between cases and controls (p < 0.01) and 30% of cases scored “poor” appetites. Cachexia was present in 60% of cases. Albumin, lymphocytes, platelets, Hb, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), CRP, TNFα, all at p < 0.01, neutrophil to lymphocyte ratio (NLR) (p = 0.02), IL-6 (p < 0.04), and IL-8 (p = 0.02) differed significantly between cases and controls. No difference was found for CXCL5 or H3Cit. Albumin NLR, Hb, PLR, SII, TNFα, IL-8, and CRP showed significant relationships with all aspects of QoL. QL-FS was significantly related to CXCL5 (p = 0.04), significant relationships with FAACT A/CS-12 included: NLR (p = 0.002), Hb (p < 0.001), and PLR (p < 0.01). NLR, PLR, SII, TNFα, IL-6, IL-8, and CRP correlated positively to cachexia and albumin while Hb and lymphocyte count correlated negatively to cachexia. Conclusion: CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia, nor significantly related to QoL, appetite or cachexia. Albumin, NLR, Hb, PLR, SII, TNFα, IL-8, and CRP were reliable indicators of QoL, appetite, and cachexia. Future research should include other novel biomarkers namely growth differentiation factor-15 (GDF-15), fibroblast growth factor 21 (FGF-21), fractakline, interferon gamma (IFN-y), IL-16, macrophage colony stimulating factor (M-CSF), and macrophage procoagulant–inducing factor (MPIF). [ABSTRACT FROM AUTHOR]

Background: Older adults with cancer are a growing population requiring tailored care to achieve optimum treatment outcomes. Their care is complicated by under-recognised and under-treated wasting disorders: malnutrition, sarcopenia, and cachexia. We aimed to investigate the prevalence, overlap, and patients' views and experiences of malnutrition, sarcopenia, and cachexia, in older adults with cancer. Methods: Mixed-methods study with cross-sectional study and qualitative interviews. Interviews were thematically analysed through a phenomenological lens, with feedback loop analysis investigating relationships between themes and findings synthesised using modified critical interpretative synthesis. Findings: n = 30 were screened for malnutrition, sarcopenia, and cachexia, n = 8 completed semi-structured interviews. Eighteen (60.0%) were malnourished, 16 (53.3%) sarcopenic, and 17 (56.7%) cachexic. One or more condition was seen in 80%, and all three in 30%. In univariate analysis, Rockwood clinical frailty score (OR 2.94 [95% CI: 1.26–6.89, p = 0.013]) was associated with sarcopenia, reported percentage meal consumption (OR 2.28 [95% CI: 1.24–4.19, p = 0.008]), and visible wasting (OR 8.43 [95% CI: 1.9–37.3] p = 0.005) with malnutrition, and percentage monthly weight loss (OR 8.71 [95% CI: 1.87–40.60] p = 0.006) with cachexia. Screening tools identified established conditions rather than 'risk'. Nutritional and functional problems were often overlooked, overshadowed, and misunderstood by both patients and (in patients' perceptions) by clinicians; misattributed to ageing, cancer, or comorbidities. Patients viewed these conditions as both personal impossibilities, yet accepted inevitabilities. Conclusion: Perceptions, identification, and management of these conditions needs to improve, and their importance recognised by clinicians and patients so those truly 'at risk' are identified whilst conditions are more remediable to interventions. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) has been long considered a key player in cancer cachexia. It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia. However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, is a critical mediator of IL-6 function in cancer cachexia in male mice. We find that circulating IL-6 can rapidly enter the AP and activate neurons in the AP and its associated network. Peripheral tumor, known to increase circulating IL-6, leads to elevated IL-6 in the AP, and causes potentiated excitatory synaptic transmission onto AP neurons and AP network hyperactivity. Remarkably, neutralization of IL-6 in the brain of tumor-bearing mice with an anti-IL-6 antibody attenuates cachexia and the hyperactivity in the AP network, and markedly prolongs lifespan. Furthermore, suppression of Il6ra, the gene encoding IL-6 receptor, specifically in AP neurons with CRISPR/dCas9 interference achieves similar effects. Silencing Gfral-expressing AP neurons also attenuates cancer cachectic phenotypes and AP network hyperactivity. Our study identifies a central mechanism underlying the function of peripheral IL-6, which may serve as a target for treating cancer cachexia. Elevation of IL-6 during cancer progression has been shown to drive cancer cachexia, however, while brain dysfunction has been reported, the underlying mechanism is unclear. Here, the authors identify neurons in the area postrema as a mediator of peripheral IL-6 in preclinical models of cancer cachexia. [ABSTRACT FROM AUTHOR]

Objective: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. Methods: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg−1•d−1), MPA + low-dose (20 mg•kg−1•d−1) JP (L-JP), MPA + medium-dose (30 mg•kg−1•d−1) JP (M-JP), and MPA + high-dose (40 mg•kg−1•d−1) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. Results: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro. Conclusions: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system). [ABSTRACT FROM AUTHOR]

The article focuses on evaluating a new scoring system for diagnosing protein energy wasting (PEW) in children with chronic kidney disease (CKD), particularly emphasizing the importance of lean body mass (LBM) measured by dual-energy x-ray absorptiometry (DEXA) as diagnostic biomarker. Topics include the criteria and biomarkers for diagnosing PEW, the utility of LBM measurement by DEXA in detecting subclinical PEW, and considerations regarding the limitations and practicality of using DEXA.

Purpose: In this systematic review, we included randomized controlled trials from 2004 to 2021 to determine the effect of individual dietary counseling for patients with head and neck cancer, specifically, nutritional outcome, morbidity, and quality of life (QOL), during and after chemo- and chemoradiotherapy. Methods: In October 2023, a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychInfo, CINAHL, and Medline) to find studies concerning the use and effectiveness of intensive nutritional care on head and neck cancer patients. Results: From all 2565 search results, 6 studies with 685 head and neck cancer patients were included in this systematic review. The patients were treated with radiotherapy or radiochemotherapy. The therapy concepts include intensive nutritional support from a dietician. Outcomes were nutritional status, body composition, quality of life, and adverse effect. All studies had low quality, high risk of bias, and reported heterogeneous results: some studies reported significant improved nutrition status, body composition and quality of life, while other studies did not find any changes concerning these endpoints. Conclusion: Due to the very heterogeneous results and methodical limitations of the included studies, a clear statement regarding the effectiveness of intensive nutritional therapy of head and neck cancer patients is not possible. Further well-planned studies are needed. [ABSTRACT FROM AUTHOR]

Drug dose response curves are ubiquitous in cancer biology, but these curves are often used to measure differential response in first-order effects: the effectiveness of increasing the cumulative dose delivered. In contrast, second-order effects (the variance of drug dose) are often ignored. Knowledge of second-order effects may improve the design of chemotherapy scheduling protocols, leading to improvements in tumor response without changing the total dose delivered. By considering treatment schedules with identical cumulative dose delivered, we characterize differential treatment outcomes resulting from high variance schedules (e.g. high dose, low dose) and low variance schedules (constant dose). We extend a previous framework used to quantify second-order effects, known as antifragility theory, to investigate the role of drug pharmacokinetics. Using a simple one-compartment model, we find that high variance schedules are effective for a wide range of cumulative dose values. Next, using a mouse-parameterized two-compartment model of 5-fluorouracil, we show that schedule viability depends on initial tumor volume. Finally, we illustrate the trade-off between tumor response and lean mass preservation. Mathematical modeling indicates that high variance dose schedules provide a potential path forward in mitigating the risk of chemotherapy-associated cachexia by preserving lean mass without sacrificing tumor response. [ABSTRACT FROM AUTHOR]

Patients with advanced cancer are frequently burdened with a severe sensation of fatigue called cancer-related fatigue (CRF). CRF is induced at various stages and treatments, such as cachexia and chemotherapy, and reduces the overall survival of patients. Objective and quantitative assessment of CRF could contribute to the diagnosis and prediction of treatment efficacy. However, such studies have not been intensively performed, particularly regarding metabolic profiles. Here, we conducted plasma metabolomics of 15 patients with urological cancer. The patients with and without fatigue, including those with cachexia or chemotherapy-induced fatigue, were compared. Significantly lower concentrations of valine and tryptophan were observed in fatigued patients than in non-fatigued patients. In addition, significantly higher concentrations of polyamine pathway metabolites were observed in patients with fatigue and cachexia than in those without cachexia. Patients with exacerbated fatigue due to chemotherapy showed significantly decreased cysteine and methionine metabolism before chemotherapy compared with those without fatigue exacerbation. These findings suggest that plasma metabolic profiles could help improve the diagnosis and monitoring of CRF. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia is a multifactorial syndrome leading to progressive functional impairment. How cachexia affects the treatment course of chemotherapy in patients with pancreatic cancer has not been well understood. Methods: This is an exploratory, retrospective, observational cohort study using the Japanese medical claims database from Medical Data Vision Co., Ltd. The study population included patients diagnosed with pancreatic cancer in whom first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) was initiated between October 1, 2018, and September 30, 2020. In this study, we defined patients with cancer cachexia as those who had a weight loss of ≥ 5% in the preceding 6 months. The primary outcome was time-to-treatment failure (TTF). The observation period was six months from the initiation of first-line FFX or GnP treatment. Results: A total of 1897 patients (421 patients into the cachexia group; 1476 patients into the non-cachexia group) were analyzed in this study. The median TTF was 121 days (95% confidence interval [CI] 94–146) in the cachexia group and 143 days (95% CI 134–152) in the non-cachexia group. The hazard ratio for TTF of the cachexia versus non-cachexia group was 1.136 (95% CI 0.979–1.319). The median number of doses was two doses fewer in the cachexia group than in the non-cachexia group for both FFX and GnP. Conclusion: Cancer cachexia was suggested to be associated with shorter TTF and a reduced number of doses in patients with pancreatic cancer who received first-line FFX or GnP treatment. Clinical Trial Registration clinicaltrials.jp: UMIN000045820. [ABSTRACT FROM AUTHOR]

The 5/6 nephrectomy and adenine-induced nephropathy mouse models have been extensively used to study Chronic Kidney Disease (CKD)-related cachexia. One common caveat of these CKD models is the cross-sectional nature of comparisons made versus controls. We here performed a comprehensive longitudinal assessment of body composition and energy metabolism in both models. The most striking finding is that weight loss is largely driven by reduced food intake which promotes rapid loss of lean and fat mass. However, in both models, mice catch up weight and lean mass a few days after the surgery or when they are switched back to standard chow diet. Muscle force and mass are fully recovered and no sign of cachexia is observed. Our data demonstrate that the time-course of kidney failure and weight loss are unrelated in these common CKD models. These data highlight the need to reconsider the relative contribution of direct and indirect mechanisms to muscle wasting observed in CKD. Chronic kidney disease (CKD) includes loss of renal function combined with numerous other health complications. An investigation of CKD-associated complication of cachexia in mouse models highlights that the time-course of renal failure and muscle wasting are not causal in these models. [ABSTRACT FROM AUTHOR]

Cancer provokes systemic diseases through three possible mechanisms: 1) Distal metastasis in multiple tissues and organs, which directly causes functional damage and impairment of involved organs; 2) Paraneoplastic syndrome (PNS) that affects multiple organ systems, including the endocrine, gastrointestinal, hematologic, neurologic, dermatologic, and ophthalmologic systems; and 3) Cancer cachexia (CCA) or self-wasting syndrome characterized by anorexia, progressive bodyweight loss, adipose atrophy, and muscle atrophy. While cancer metastasis has received considerable attention for comprehensive research, PNS and CCA remain relatively overlooked. At the time of this writing, effective treatments of PNS and CCA in human cancer patients are lacking. This review focuses on discussing mechanistic insights into PNA and CCA and current advances in development of new possible therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). Methods: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. Results: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3–4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1–2 were poor prognostic factors. Conclusions: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3–4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a disorder that affects patient outcomes. The present study prospectively evaluated the prognostic value of the cachexia index (CXI) in elderly patients with non-Hodgkin's lymphoma (NHL). We prospectively analyzed 51 elderly patients who were diagnosed with NHL at our institution. CXI was calculated as follows: CXI = SMI × Alb/NLR (SMI: skeletal muscle index, Alb: serum albumin, NLR: neutrophil-to-lymphocyte ratio). SMI was measured by a bioelectrical impedance analysis (BIA) using the InBody 720. We determined the sex-specific cutoff values of the CXI by a receiver operating characteristic curve analysis and divided all patients into low- and high-CXI groups. The median age at the diagnosis was 78 years (60–93 years), and 28 (55%) were male. The histologic subtypes were B-cell lymphoma in 49 patients and T-cell lymphoma in 2. Twenty-eight (55%) patients were categorized into the high-CXI group, and 23 (45%) were categorized into the low-CXI group. The overall survival (OS) in the low-CXI group was significantly shorter than that in the high-CXI group (3-year OS, 70.4% vs. 95.7%, p = 0.007). Among 23 patients with DLBCL, patients with low-CXI had shorter OS than those with high-CXI (3-year OS, 55.6% vs. 92.9%, p = 0.008). On the other hand, sarcopenia had less impact on the clinical outcome of DLBCL patients. Low-CXI was associated with poor outcomes in elderly NHL and the CXI may be a clinical useful index for predicting prognosis. Further large prospective studies are needed to verify this conclusion. [ABSTRACT FROM AUTHOR]

The article discusses the impact of cachexia, a condition characterized by weight loss and muscle wasting, on the quality of life and survival of lung cancer patients. It highlights the high prevalence of cachexia in lung cancer patients and the need for effective treatment approaches. The article introduces a research project called LuCaPET, which aims to use advanced imaging techniques and artificial intelligence algorithms to detect metabolic patterns associated with cachexia in lung cancer patients. The project also addresses the ethical challenges of using AI in clinical decision-making and aims to make the AI-driven models transparent and comprehensible for clinicians. The ultimate goal of the project is to improve the diagnosis and treatment of cachexia in lung cancer patients and enhance their quality of life and survival. [Extracted from the article]

Rationale: Unintentional weight loss and malnutrition are common among cancer patients. Malnutrition has been associated with impaired health-related quality of life, less well-tolerated chemotherapy regimens and shorter life duration. In Belgium there is a lack of epidemiological data on malnutrition in oncology patients at advanced stages of the disease. Methods: Malnutrition assessment data was collected through a prospective, observational study in 328 patients who started a neoadjuvant anticancer therapy regimen or who started 1st, 2nd or 3rd line anticancer therapy for a metastatic cancer via 3 visits according to regular clinical practice (baseline visit (BV) maximum 4 weeks before start therapy, 1st Follow up visit (FUV1) ± 6 weeks after start therapy, FUV2 ± 4 months after start therapy). Malnutrition screening was evaluated using the Nutritional Risk Screening score 2002 (NRS-2002)and the diagnosis of malnutrition by the GLIM criteria. In addition, SARC-F questionnaire and Fearon criteria were used respectively to screen for sarcopenia and cachexia. Results: Prevalence of malnutrition risk at BV was high: 54.5% of the patients had a NRS ≥ 3 (NRS 2002) and increased during the study period (FUV1: 73.2%, FUV2: 70.1%). Prevalence of malnutrition based on physician subjective assessment (PSA) remained stable over the study period but was much lower compared to NRS results (14.0%—16.5%). At BV, only 10% of the patients got a nutrition plan and 43.9% received ≤ 70% of nutritional needs, percentage increased during FU period (FUV1: 68.4%, FUV2: 67.6%). Prevalence of sarcopenia and cachexia were respectively 12.4% and 38.1% at BV and without significant variation during the study period, but higher than assessed by PSA (11.6% and 6.7% respectively). Figures were also higher compared to PSA. There were modifications in cancer treatment at FUV1 (25.2%) and at FUV2 (50.8%). The main reasons for these modifications at FUV1 were adverse events and tolerability. Patient reported daily questionnaires of food intake showed early nutritional deficits, preceding clinical signs of malnutrition, and therefore can be very useful in the ambulatory setting. Conclusions: Prevalence of malnutrition and cachexia was high in advanced cancer patients and underestimated by physician assessment. Earlier and rigorous detection of nutritional deficit and adjusted nutritional intake could lead to improved clinical outcomes in cancer patients. Reporting of daily caloric intake by patients was also very helpful with regards to nutritional assessment. [ABSTRACT FROM AUTHOR]

Key Summary Points: Aim: The present study aimed to investigate potential confounders of the obesity paradox in older patients following transcatheter aortic valve replacement (TAVR) for severe aortic stenosis. Findings: The obesity paradox was observed in older patients following TAVR. Cachexia may reflect higher mortality in patients with lower BMI and higher subcutaneous fat accumulation (SFA) may represent lower mortality in those with higher BMI. Message: Considering higher mortality in lower BMI with cachexia, prevention or treatment of the comorbidity would be important in older patients following TAVR. Purpose: A higher body mass index (BMI) is associated with lower mortality in older patients following transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis. The current study aimed to investigate potential confounders of association between BMI and prognosis. Methods: The retrospective single-center study included consecutive patients following TAVR and excluded those in whom subcutaneous fat accumulation (SFA), visceral fat accumulation (VFA), and major psoas muscle (MPM) volume were not assessed by computed tomography. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities. Results: After 2 patients were excluded, 234 (age, 86 ± 5 years; male, 77 [33%]; BMI, 22.4 ± 3.8 kg/m2; SFA, 109 (54–156) cm2; VFA, 71 (35–115) cm2; MPM, 202 (161–267) cm3; cachexia, 49 [21%]) were evaluated. SFA and VFA were strongly correlated with BMI (ρ = 0.734 and ρ = 0.712, respectively), whereas MPM was weakly correlated (ρ = 0.346). Two-year all-cause mortality was observed in 31 patients (13%). Higher BMI was associated with lower mortality (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.77–0.95). A similar result was observed in the multivariate model including SFA (aHR in an increase of 20 cm2, 0.87; 95% CI, 0.77–0.98) instead of BMI, whereas VFA was not significant. Cachexia was a worse predictor (aHR, 2.51; 95% CI 1.11–5.65). Conclusions: Association of higher BMI with lower mortality may be confounded by SFA in older patients following TAVR. Cachexia might reflect higher mortality in patients with lower BMI. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARα target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARα by fenofibrate, a PPARα agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia. Cancer cachexia is a systemic syndrome characterized by dramatic weight loss and decline in adipose tissue and skeletal muscle mass. Here, the authors show that overexpression of leukemia inhibitory factor (LIF), a secreted cytokine, suppresses de novo lipogenesis and induces cachexia in mice. [ABSTRACT FROM AUTHOR]

Purpose: Emerging biomarkers of cancer cachexia and their roles in sarcopenia and prognosis are poorly understood. Baseline assessments of anthropometrics, sarcopenia, cachexia status and biomarkers of cachexia were measured in patients with advanced cancer and healthy controls. Thereafter, relationships of the biomarkers with cachexia and sarcopenia were explored. Methods: A prospective case–control design was used, including 40 patients with advanced cancer and 40 gender, age-matched controls. Bioelectrical impedance [skeletal muscle index (SMI)] and hand dynamometry [hand grip strength (HGS)] assessed sarcopenia and a validated tool classified cancer cachexia. Albumin, lymphocyte and platelet counts, haemoglobin, C-reactive protein (CRP), pro-inflammatory cytokines/chemokines and citrullinated histone H3 (H3Cit) were measured. Results: Patients had significantly lower SMI (6.67 kg/m2 versus 7.67 kg/m2, p = < 0.01) and HGS (24.42 kg versus 29.62 kg) compared to controls, with 43% being sarcopenic. Significant differences were found for albumin, lymphocyte and platelet counts, haemoglobin, CRP, and tumour necrosis factor α (TNFα), (p < 0.01). Interleukin (IL)-6 (p < 0.04), IL-8 (p = 0.02), neutrophil/lymphocyte ratio (NLR), p = 0.02, platelet/lymphocyte (PLR) ratio, p < 0.01 and systemic immune inflammatory index (SII), p < 0.01 differed significantly. No difference was observed for CXC motif chemokine ligand 5 [CXCL5 or epithelial neutrophil-activating peptide 78 (ENA78)] or H3Cit. Albumin and haemoglobin correlated negatively with total protein, skeletal muscle mass and SMI (all p < 0.01). The presence of sarcopenia associated significantly with albumin, haemoglobin and CRP. Conclusion: Significant relationships and differences of haemoglobin, CRP and albumin supports future use of these biomarkers in cancer cachexia. CXCL5 and H3Cit as valuable biomarkers in cancer cachexia remains to be defined. [ABSTRACT FROM AUTHOR]

Purpose: Anamorelin, a selective ghrelin receptor agonist, has been approved for pancreatic cancer treatment in Japan. We aimed to investigate whether systemic inflammation, represented by the neutrophil–lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP)-albumin ratio (CAR), could predict the effect of anamorelin in patients with advanced pancreatic cancer. Methods: This study included 31 patients who had received anamorelin for advanced pancreatic cancer between 2021 and 2023. Patients’ NLR, PLR, LMR, and CAR were evaluated before anamorelin administration. The patients were classified as responders and non-responders based on whether they gained body weight after 3 months of anamorelin administration. We investigated the association between systemic inflammation and anamorelin efficacy using a univariate analysis. Results: Twelve (39%) patients were non-responders. A high serum CRP level (p = 0.007) and high CAR (p = 0.013) was associated with non-response to anamorelin. According to the receiver operating characteristics analysis, the CAR cutoff value was 0.06, and CAR ≥ 0.06 was a risk factor (odds ratio, 5.6 [95% confidence interval 1.2–27.1], p = 0.032) for non-response to anamorelin. Conclusion: CAR can be a predictor of non-response to anamorelin in patients with advanced pancreatic cancer, suggesting the importance of a comprehensive assessment of the inflammatory status. [ABSTRACT FROM AUTHOR]

Cancer-related anorexia/cachexia syndrome (CACS) is characterized by anorexia and loss of body weight. Evidence is insufficient to strongly endorse any pharmacologic agent for the treatment of CACS. In this systematic review, we assessed the efficacy of oral anamorelin treatment for patients with CACS. On July 6, 2022, we systematically searched the following databases for randomized controlled trials (RCTs) of adults with CACS comparing oral anamorelin versus placebo: CENTRAL, PubMed, EMBASE, and ICHUSHI. The primary outcomes were total body weight (TBW), patient-reported quality of life (QOL), and adverse events (AEs). Secondary outcomes included lean body mass (LBM), overall survival (OS), non-dominant hand grip strength (HGS), and appetite. We included seven RCTs with a total of 1944 CACS patients. Anamorelin significantly increased TBW (mean difference (MD) 1.73, 95% confidence interval (CI) 1.34–2.13, p < 0.00001), LBM (MD 1.06, 95% CI 0.30–1.81, p = 0.006), and QOL (standardized mean difference (SMD) 0.16, 95% CI 0.04–0.27, p = 0.006) compared with placebo without a significant difference in all AEs, severe AEs, OS, HGS or appetite. Anamorelin may be an effective treatment for CACS patients; however, further studies are needed to confirm the efficacy and safety of this drug. [ABSTRACT FROM AUTHOR]

Purpose: Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, is an unremitting problem for cancer patients. Anamorelin has become available for cancer-associated cachexia, but early discontinuation is common in clinical practice. This study aimed to explore factors related to the early discontinuation of anamorelin and its relationship to survival. Patients and methods: This prospective, observational study of multimodal clinical practice involved patients who took anamorelin (100 mg) for cancer-associated cachexia at Aichi Medical University Hospital between 14 May 2021 and 31 March 2022. In July 2022, clinical data were extracted from electronic clinical records. Patients who discontinued anamorelin less than 4 weeks after initiation were defined as the early discontinuation group, and their clinical data and survival time were compared with those of the continuation group. This study was approved by the Ethics Committee of the university (approval no. 2021-124). Results: Of the 42 patients treated with anamorelin, 40 (median age 72.5 years, median BMI 18.7 kg/m2) were analyzed, including 13 with non-small cell lung cancer, and 12 with pancreatic, 8 with colorectal, and 7 with gastric cancers. On univariate analysis, the early discontinuation group included more patients with worse performance status (PS) (p=0.028), low prognostic nutritional index (PNI) (p=0.001), and no concomitant anticancer drugs (p=0.003). On multivariate analysis, PS and PNI were related to anamorelin continuation. Survival time was significantly shorter in the early discontinuation group (p=0.039). Conclusion: Worse PS and low PNI were associated with early discontinuation of anamorelin. Longer survival time was observed in the continuation group. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings. Cancer cachexia is a multifactorial metabolic syndrome affecting a large fraction of patients with advanced cancer. Here the authors report a decrease in B vitamin-related liver enzymes in mouse models and gastric cancer patients with cachexia. [ABSTRACT FROM AUTHOR]

Cancer cachexia is characterized by weight loss and skeletal muscle wasting. Based on the up-regulation of catabolism and down-regulation of anabolism, here we showed genetic mutation-mediated metabolic reprogramming in the progression of cancer cachexia by screening for metabolites and investigating their direct effect on muscle atrophy. Treatment with 93 μM D-2-hydroxyglutarate (D2HG) resulted in reduced myotube width and increased expression of E3 ubiquitin ligases. Isocitrate Dehydrogenase 1 (IDH1) mutant patients had higher D2HG than non-mutant patients. In the in vivo murine cancer cachexia model, mutant IDH1 in CT26 cancer cells accelerated cachexia progression and worsened overall survival. Transcriptomics and metabolomics revealed a distinct D2HG-induced metabolic imbalance. Treatment with the IDH1 inhibitor ivosidenib delayed the progression of cancer cachexia in murine GL261 glioma model and CT26 colorectal carcinoma models. These data demonstrate the contribution of IDH1 mutation mediated D2HG accumulation to the progression of cancer cachexia and highlight the individualized treatment of IDH1 mutation associated cancer cachexia. IDH1 mutation mediated D2HG accumulation contributes to the progression of cancer cachexia and muscle atrophy. IDH1 inhibitor ivosidenib delayed the progression of cancer cachexia in murine GL261 glioma model and CT26 colorectal carcinoma models. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic significance of the cachexia index, a novel biomarker of cancer cachexia, remains unclear in colorectal cancer; we, therefore, evaluated this relationship. Methods: This retrospective cohort study included 306 patients with stage I–III colorectal cancer who underwent R0 resection between April 2010 and March 2020. The cachexia index was calculated as (skeletal muscle index [cm2/m2] × serum albumin level [g/dL])/neutrophil-to-lymphocyte ratio. The overall and disease-free survival rates were analyzed using a Cox proportional hazards model. Results: A low cachexia index was found in 94 patients. This group had significantly lower disease-free survival and overall survival than the high-cachexia index group (5-year survival, 86.3% vs. 63.1%, p < 0.01; 87.9% vs. 67.2%, p < 0.01). Multivariate analyses showed that T3 or T4 (hazard ratio [HR]: 2.56; 95% confidence interval CI 1.04–6.25, p = 0.039), stage III (HR: 3.77; 95% CI 1.79–7.93, p < 0.01), and a low cachexia index (HR: 2.27; 95% CI 1.31–3.90, p = 0.003) were significant independent predictors of the disease-free survival. CA19-9 ≥ 37.0 ng/mL (HR: 2.68; 95% CI: 1.37–5.24, p = 0.004), stage III (HR: 2.57; 95% CI 1.34–4.92, p = 0.004), and a low cachexia index (HR: 2.35; 95% CI 1.31–4.21, p = 0.004) were significant independent predictors of the overall survival. Conclusion: A low cachexia index might be a long-term prognostic factor of colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of ambient temperature (AT) on the evolution of bodyweight in patients with heterogeneous types of cancer in advanced stages of the disease (stages III and IV) and anorexia- cachexia syndrome (ACS). Methods: A prospective naturalistic multicenter study of patients undergoing oncological treatment at four hospitals during a three-year period (2017–2020) in the Autonomous Community of Extremadura in southwestern Spain with a continentalized Mediterranean climate of mild and relatively rainy winters, and particularly hot and sunny summers. Bodyweight changes were obtained from the medical records of 84 oncological patients (59 men and 25 women, age range 37–91 yrs). Mean monthly AT was used to examine the association of weight changes across cold and warm bimesters -BIMs (December and January, vs. July and August), Trimesters -TRIMs (July to September vs. December to February), and Semesters -SEMs (May to October vs. November to April). Weight changes between two consecutive weight measures were categorized as weight gain, weight loss, or no weight change. Differences across cold and warm seasons were analysed using parametric (ANOVA), and nonparametric statistics (Chi-square and binomial z tests). An alpha-rate of 0.05 was used for all analyses. Results: A weight loss trend was observed during BIMs cold periods in comparison to warm ones (p 0.04). However, differences in average bodyweight were not significant. The negative impact of cold periods was more marked in men than in women, (p = 0.05; p = 0.03, for cold vs. warm BIMs and TRIMs, respectively). In contrast, significantly higher weight gain percentages were found in women during warm TRIMs and SEMs (p = 0.03, and p = 0.01, respectively). As for the number of patients dying during the study (N = 56; 39 men, 17 women), there were a significant interaction between temperature (cold/warm), and mean weight F (1, 499) = 6.06, p = 0.01, which revealed a pattern of weight loss in the cold semester as opposed to weight gain during the warm SEM months. Conclusions: AT temperature modulated body weight changes in patients with advanced oncological disease and ACS. Two main limitations of the study were the absence of information on diets as a moderating factor of weight loss/gain, and the lack of the patients' weight measurements closest to the date of diagnosis prior to admittance to the study. As for the practical implications, it remains to be seen whether an adjunctive heat supply will serve a buffering effect on weight loss during colder seasons for patients with advanced cancer and ACS. [ABSTRACT FROM AUTHOR]

Cancer-associated cachexia is a multi-organ weight loss syndrome, especially with a wasting disorder of adipose tissue and skeletal muscle. Small extracellular vesicles (sEVs) serve as emerging messengers to connect primary tumour and metabolic organs to exert systemic regulation. However, whether and how tumour-derived sEVs regulate white adipose tissue (WAT) browning and fat loss is poorly defined. Here, we report breast cancer cell-secreted exosomal miR-204-5p induces hypoxia-inducible factor 1A (HIF1A) in WAT by targeting von Hippel-Lindau (VHL) gene. Elevated HIF1A protein induces the leptin signalling pathway and thereby enhances lipolysis in WAT. Additionally, exogenous VHL expression blocks the effect of exosomal miR-204-5p on WAT browning. Reduced plasma phosphatidyl ethanolamine level is detected in mice lack of cancer-derived miR-204-5p secretion in vivo. Collectively, our study reveals circulating miR-204-5p induces hypoxia-mediated leptin signalling pathway to promote lipolysis and WAT browning, shedding light on both preventive screenings and early intervention for cancer-associated cachexia. Tumour cells can communicate with cells from distant organs through extracellular vesicles. Here the authors show that breast cancer cells derived exosomal miR-204-5p induce leptin signalling pathway in white adipose tissue to promote cancer-associated cachexia. [ABSTRACT FROM AUTHOR]

Stephan Schätzl was the parish priest of Viechtwang, Upper Austria. He lived in the aftermath of the Peace of Augsburg in a period of schism between Roman Catholics and Lutherans. His portrait, depicted only 6 days before his demise in 1590, shows that he had extreme ante mortem cachexia. Documentary sources detailed his life and ill-health and it is proposed that he had chronic gastro-duodenal ulcerative disease which ultimately led his to death. [ABSTRACT FROM AUTHOR]

Purpose: Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia status and clinical responses in head and neck cancer patients. Methods: Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Plasma concentrations of total and free aprepitant and ND-AP were determined at 24 h after a 3-day aprepitant treatment. The clinical responses to aprepitant and degrees of cachexia status were assessed using a questionnaire and Glasgow Prognostic Score (GPS). Results: Serum albumin level was negatively correlated with the plasma concentrations of total and free aprepitant but not ND-AP. The serum albumin level had a negative correlation with the metabolic ratio of aprepitant. The patients with GPS 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant. Conclusion: Cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: To identify the influence of sarcopenia and cachexia in prognostic markers in COVID-19 inpatients. Findings: Sarcopenia is presented as a risk factor for mortality in COVID-19 inpatients. Message: The accurate evaluation of nutritional abnormalities in hospitalized patients diagnosed with COVID-19 may help to reduce the risk for adverse outcomes. Purpose: SARS-CoV-2 infection can lead to various manifestations beyond an inflammatory response, such as anorexia, hyposmia, and other symptoms that may increase the risk of nutritional disorders. Sarcopenia and cachexia are conditions that appear to influence COVID-19 evolution. Thus, this study aimed to evaluate sarcopenia and cachexia in hospitalized patients with COVID-19, verifying their clinical impacts and relationship with prognostic markers. Methods: This is a case-control study involving inpatients with and without a COVID-19 diagnosis. The occurrence of sarcopenia was evaluated according to European Working Group on Sarcopenia 2 criteria. Cachexia was evaluated according to (Evans et al. in Clin Nutr 27:793–799, 2008) criteria. Inflammatory markers and the 4C Mortality Score were evaluated. Results: Our study included 96 individuals, divided into two groups: COVID-19 (n = 32) and control (n = 64). The mean age of the COVID-19 group was 63.3 ± 11.8 years, and the control group had a mean age of 64.3 ± 5.5 years. No significant differences in mean age were found between the groups. The prevalence of sarcopenia and cachexia in patients with COVID-19 was 21.9% and 28.1%, respectively, while in the control group, it was 29.7% and 26.6%, respectively. Sarcopenic patients with COVID-19 had a higher risk of death (4C Mortality Score) (p = 0.038). The occurrence of sarcopenia or cachexia within the COVID-19 group was not associated with inflammatory biomarkers or a higher number of COVID-19 symptoms (p > 0.05). Conclusion: The presence of sarcopenia among COVID-19 patients increased the risk of mortality. [ABSTRACT FROM AUTHOR]

Purpose of the Review: The purpose of this review is to summarize the role of the osteocyte in muscle atrophy in cancer patients, sarcopenia, spinal cord injury, Duchenne's muscular dystrophy, and other conditions associated with muscle deterioration. Recent Findings: One type of bone cell, the osteocyte, appears to play a major role in muscle and bone crosstalk, whether physiological or pathological. Osteocytes are cells living within the bone-mineralized matrix. These cells are connected to each other by means of dendrites to create an intricately connected network. The osteocyte network has been shown to respond to different types of stimuli such as mechanical unloading, immobilization, aging, and cancer by producing osteocytes-derived factors. It is now becoming clear that some of these factors including sclerostin, RANKL, TGF-β, and TNF-α have detrimental effects on skeletal muscle. Summary: Bone and muscle not only communicate mechanically but also biochemically. Osteocyte-derived factors appear to contribute to the pathogenesis of muscle disease and could be used as a cellular target for new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Viroids are important citrus pathogens, and cachexia disease is caused by pathogenic variants, CVd-IIb and CVd-IIc, of hop stunt viroid (HSVd). In September 2020, 96 samples of kumquat (Citrus japonica) and limequat (C. japonica x C. aurantifolia) trees showing suspected symptoms were collected in Mazandaran Province, Iran. Biological indexing was performed under greenhouse conditions using scion obtained from 19 selected samples on 'Etrog' citron Arizona 861-S-1 (Citrus medica) and Parson's Special Mandarin (C. reticulata), both grafted on rough lemon (C. jambhiri), as a common indicator plant for citrus viroids and specific indicator of cachexia, respectively. Twelve months after inoculation, Parson's gum accumulation at the bud union was seen in only two isolates, while symptoms of viroid infection, including petiole bending, epinasty, twisting, and yellowing of the leaf tip were observed in all 'Etrog' citron plants inoculated with tissues from the trees with cachexia symptoms. Total RNA extraction followed by one-step RT-PCR and DNA sequencing showed that a pathogenic variant (CVd-IIb) was present in all of the sequenced isolates from symptomatic kumquat and limequat trees. Asymptomatic limequat trees were free of HSVd infection, while non-pathogenic variants, CVd-IIa, were found in asymptomatic and symptomatic kumquat trees. The phylogenetic analysis showed that isolates K0S2 and K2C34 were located in the CVd-IIa group, while isolates K1H5, K2S4, K2C28, K3S1, and L3Sa13 grouped in the CVd-IIb group. In addition to HSVd, citrus exocortis viroid (CEVd), citrus bent leaf viroid (CBLVd), citrus dwarfing viroid (CDVd) and citrus bark cracking viroid (CBCVd) infections were confirmed in several kumquat trees. The relationship between cachexia symptoms, HSVd variants, and mixed infection is discussed. To the best of our knowledge, this is the first report of HSVd infection of limequats in the world and of kumquats in Iran. [ABSTRACT FROM AUTHOR]

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients. The loss of nicotinamide adenine dinucleotide is reported to be associated with muscle mitochondrial dysfunction in murine cancer models. Here the authors show that niacin supplementation improves mitochondrial metabolism and reduces muscle wasting in mouse models of cachexia. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia (CC) is a debilitating syndrome severely impacting patients' quality of life and survivorship. We aimed to investigate the health care professionals' (HCPs') experiences of dealing with CC. Methods: Survey questions entailed definitions and guidelines, importance of CC management, clinician confidence and involvement, screening and assessment, interventions, psychosocial and food aspects. The online survey was disseminated through Australian and New Zealand palliative care, oncology, allied health and nursing organisations. Frequencies were reported using descriptive statistics accounting for response rates. Associations were examined between variables using Fisher's exact and Pearson's chi-square tests. Results: Over 90% of the respondents (n = 192) were medical doctors or nurses. Over 85% of the respondents were not aware of any guidelines, with 83% considering ≥ 10% weight loss from baseline indicative of CC. CC management was considered important by 77% of HCPs, and 55% indicated that it was part of their clinical role to assess and treat CC. In contrast, 56% of respondents were not confident about managing CC, and 93% believed formal training in CC would benefit their clinical practice. Although formal screening tools were generally not used (79%), 75% of respondents asked patients about specific symptoms. Antiemetics (80%) and nutritional counselling (86%) were most prescribed or recommended interventions, respectively. Conclusion: This study underlines the deficiencies in knowledge and training of CC which has implications for patients' function, well-being and survival. HCP training and a structured approach to CC management is advocated for optimal and continued patient care. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate and develop imaging biomarkers for the diagnosis of cancer-associated cachexia based on the organ and tissue-specific abnormal metabolisms measured by fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT. Methods: FDG PET/CT data from 390 cancer patients were analyzed retrospectively. Patients were divided into a development cohort and a validation cohort. Cachexia was defined as weight loss > 5% in 6 months or BMI < 20 and weight loss > 2%. According to the above definitions, patients were divided into cachexia and non-cachexia groups. Results of the clinical laboratory tests for metabolic levels and organ and tissue-specific FDG uptake obtained from the cachexia and non-cachexia groups were compared statistically. Logistic regression analysis was performed to identify independent variables associated with cachexia in the development cohort for generating the regression model. The performance of the model was tested using the data from a validation cohort and evaluated by area under the receiver operating characteristic curve (AUC). Results: Based on the data from the development cohort of 286 patients and a validation cohort of 104 patients, it is found that age, white blood cell count, peak standardized uptake value (SUV) of the liver, and minimum SUV of lean body mass of visceral fat and subcutaneous fat were independently associated with cachexia. The model incorporating these variables reached an AUC of 0.777 (95% confidence interval (CI): 0.721, 0.833) in the development cohort and an AUC of 0.729 (95% CI: 0.629, 0.829) in the validation cohort. Conclusion: Organ and tissue-specific abnormal glucose metabolism as measured by PET/CT can be used as a biomarker for cancer-associated cachexia. Key Points: • Patients with cancer-associated cachexia have reduced FDG uptake in the liver and increased FDG uptake in visceral fat and subcutaneous fat. • FDG uptake of the liver, visceral fat, and subcutaneous fat can be independent risk factors for identifying cancer-associated cachexia. • Cancer-associated cachexia can be classified using the model that incorporates age, white blood cell count, FDG uptake of the liver, and visceral and subcutaneous fat can diagnose with an AUC of 0.729. [ABSTRACT FROM AUTHOR]

A letter published in the International Journal of Clinical Oncology discusses the impact of cancer cachexia on survival in patients with pancreatic cancer and the efficacy of first-line chemotherapy. The letter references a study by Furuse et al. that found cancer cachexia to significantly influence time-to-treatment failure (TTF) but not overall survival (OS) in pancreatic cancer patients. The study also noted differences in the impact of different anticancer regimens, with the gemcitabine plus nab-paclitaxel (GnP) regimen showing no effect on TTF, while the FOLFIRINOX (FFX) regimen had a significant difference, likely due to its higher toxicity in cachectic patients. The letter concludes that GnP should be recommended as the first-line treatment for Japanese patients with pancreatic cancer and weight loss. [Extracted from the article]

Rheumatoid arthritis (RA) patients have a higher frequency of infections than the healthy population. The reason has yet to be explained but involves several factors, of which body composition and rheumatoid cachexia are often overlooked. This study aimed to evaluate whether patients with cachexia, measured by bioelectrical impedance vector analysis, are at an increased risk of developing infections compared with patients without cachexia. A secondary analysis of 186 women with RA enrolled in a randomized trial (ClinicalTrials.gov ID: NCT02900898, September 14, 2016) was completed. Medical records and phone calls were used to record infectious events diagnosed and treated during follow-up. Hazard ratios were calculated using Cox proportional hazard regression analysis, and a predictive model of infection was created. After 36 months of follow-up, 62 patients (26.7% non-cachectic and 44.3% cachectic, p < 0.01) developed at least one infectious event. The most common site of was the urinary tract, followed by the lungs and respiratory tract. The presence of cachexia (HR 1.90, 95% CI 1.15–3.13) and the use of glucocorticoids (HR 1.77, 95% CI 1.01–3.09) were associated with infection in univariate and multivariate models. Body mass index (BMI), smoking, and methotrexate use were not associated with a higher frequency of infections. The presence of cachexia and the use of glucocorticoids were identified as predictors of infections in a cohort of female RA patients. More extensive measurements of body composition should be performed beyond BMI in RA patients to better understand its impact and to prevent additional comorbidities and complications. Key Points • The presence of cachexia measured by bioelectrical impedance vector analysis was associated with infectious events in women with rheumatoid arthritis, whereas body mass index did not show an association. • Glucocorticoids were the only drug associated with a higher frequency of infection. None of the disease-modifying antirheumatic drugs, including methotrexate, showed an association. [ABSTRACT FROM AUTHOR]

Purpose: Taste and smell are used to enjoy meals; however, impairments of these sensory perceptions seriously impact health and eating habits. This study is aimed at investigating the impact of taste and smell disturbances on dietary intakes and cachexia-related quality of life (QOL) in patients with advanced cancer. Methods: Using a self-report questionnaire, we surveyed patients with advanced cancer undergoing treatment at 11 palliative care centers. Multivariate analyses were conducted to explore the impact of taste and smell disturbances on dietary intakes and cachexia-related QOL. Dietary intakes were assessed using the Ingesta-Verbal/Visual Analog Scale, while taste and smell disturbances were assessed using an 11-point Numeric Rating Scale (NRS). Cachexia-related QOL was assessed using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS). Results: Overall, 378 patients provided consent to participate. After excluding patients with missing data, data were analyzed for 343 patients. Among them, 35.6% (n = 122; 95% [confidence interval (CI)] 0.28–0.38) and 20.9% (n = 72; 95% CI 0.17–0.25) experienced disturbances in taste (NRS ≥ 1) and smell (NRS ≥ 1), respectively. Multivariate analyses revealed that, independent of performance status and cancer cachexia, taste and smell disturbances were significantly associated with worse dietary intakes and deteriorating FAACT ACS scores. Conclusion: More severe taste and smell disturbances were associated with poorer dietary intakes and cachexia-related QOL. Diagnosing and treating such disturbances may improve dietary intakes and cachexia-related QOL, regardless of performance status and cachexia. [ABSTRACT FROM AUTHOR]

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Background: Oesophageal cancer survivorship is afflicted by cancer cachexia related weight loss and nutrition impact symptoms. Identifying the factors which predict cancer cachexia specifically is warranted in order to identify those at risk and render the right kind of support. We aimed to assess if preoperative and postoperative body mass index (BMI) adjusted weight loss grading system (WLGS) is predictive of cancer cachexia at one year after surgery for oesophageal cancer.Methods: Data were used from a prospective nationwide cohort study on patients operated on for oesophageal cancer in Sweden between 2013 and 2018 included at one year after surgery. The study exposure is BMI adjusted weight loss graded into one of five distinct weight loss grades (grades 0-4), defined in accordance with the WLGS by combining BMI and percentage weight loss, assessed at two clinical time points: preoperative and at 6 months post-surgery for oesophageal cancer. The study outcome is subjective measures of cancer cachexia one year after surgery, assessed using the cancer-cachexia specific questionnaire EORTC QLQ-CAX24. Multivariable linear regression models calculated mean score differences (MD) with 95% confidence intervals (CI) adjusted for predefined confounders. Statistical significance at p < 0.05 together with a clinically relevant difference of 10-points in mean scores was considered as a significant difference.Results: Among a total of 232 patients, the highest grade of preoperative WLGS 4 was associated with significantly worse physical decline than lower grades of WLGS 1 (MD -10, 95% CI: -20 to -1) and WLGS 2 (MD -11, 95% CI: -20 to -2). Those with preoperative WLGS 2, 3 and 4 reported lower scores on the adequacy of information on weight loss provided to them than those with preoperative WLGS 0. Those with the highest postoperative WLGS 4 had greater eating and weight loss worry than WLGS 2 (MD -17, 95% CI: -32 to -3) and WLGS 3 (MD -11, 95% CI: -21 to -2) and worse physical decline than WLGS 0 (MD -14, 95% CI: -25 to -2).Conclusions: Higher grades of both preoperative and postoperative WLGS are predictive of cancer cachexia related physical decline one year after surgery for oesophageal cancer. Additionally, preoperative and postoperative WLGS were also predictive of inadequate information concerning weight loss and more worry regarding eating and weight loss, respectively. The WLGS may be an effective risk prediction tool for postoperative cachexia related physical decline in patients undergoing treatment for oesophageal cancer emphasizing its usability in the clinical setting. [ABSTRACT FROM AUTHOR]

Purpose of Review: Chemotherapy drugs combat tumor cells and reduce metastasis. However, a significant side effect of some chemotherapy strategies is loss of skeletal muscle and bone. In cancer patients, maintenance of lean tissue is a positive prognostic indicator of outcomes and helps to minimize the toxicity associated with chemotherapy. Bone-muscle crosstalk plays an important role in the function of the musculoskeletal system and this review will focus on recent findings in preclinical and clinical studies that shed light on chemotherapy-induced bone-muscle crosstalk. Recent Findings: Chemotherapy-induced loss of bone and skeletal muscle are important clinical problems. Bone antiresorptive drugs prevent skeletal muscle weakness in preclinical models. Chemotherapy-induced loss of bone can cause muscle weakness through both changes in endocrine signaling and mechanical loading between muscle and bone. Summary: Chemotherapy-induced changes to bone-muscle crosstalk have implications for treatment strategies and patient quality of life. Recent findings have begun to determine the role of chemotherapy in bone-muscle crosstalk and this review summarizes the most relevant clinical and preclinical studies. [ABSTRACT FROM AUTHOR]