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Abstract Sarcopenia is a risk factor for adverse clinical outcomes in chronic kidney disease (CKD) patients, including mortality. Diagnosis depends on adopted consensus definition and cutoff values; thus, prevalence rates are generally heterogeneous. We conducted a systematic review and meta‐analysis to investigate the global prevalence of sarcopenia and its traits across the wide spectrum of CKD. A systematic search was conducted using databases, including MEDLINE and EMBASE, for observational studies reporting the prevalence of sarcopenia. We considered sarcopenia according to the consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP), the Asian Working Group for Sarcopenia, the Foundation for the National Institutes of Health Sarcopenia Project, and the International Working Group on Sarcopenia (IWGS). Subgroup analyses by CKD stages, consensus, and gender were performed. Pooled prevalence was obtained from random‐effect models. A total of 140 studies (42 041 patients) across 25 countries were included in this systematic review and meta‐analyses. Global prevalence of sarcopenia was 24.5% [95% confidence interval (CI): 20.9–28.3) and did not differ among stages (P = 0.33). Prevalence varied according to the consensus definition from 11% to 30%, with no significant difference (P = 0.42). Prevalence of severe sarcopenia was 21.0% (95% CI: 11.7–32.0), with higher rates for patients on dialysis (26.2%, 95% CI: 16.6–37.1) compared to non‐dialysis (3.0%, 95% CI: 0–11.1; P

Background: Cancer-associated cachexia is a multi-organ disorder associated with progressive weight loss due to a variable combination of anorexia, systemic inflammation and excessive energy wasting. Considering the importance of immunoregulation in cachexia, it still lacks a complete understanding of the immunological mechanisms in cachectic progression. Aim of review: Our aim here is to describe the complex immunoregulatory system in cachexia. We summarize the effects and translational potential of the immune system on the development of cancer-associated cachexia and we attempt to conclude with thoughts on precise and integrated therapeutic strategies under the complex immunological context of cachexia. Key Scientific Concepts of Review: This review is focused on three main key concepts. First, we highlight the inflammatory factors and additional mediators that have been identified to modulate this syndrome. Second, we decipher the potential role of immune checkpoints in tissue wasting. Third, we discuss the multilayered insights in cachexia through the immunometabolic axis, immune-gut axis and immune-nerve axis.

This case report presents serous atrophy of bone marrow (SABM) in a cachexic patient with metastatic squamous cell carcinoma who had undergone radiotherapy. The unique magnetic resonance imaging (MRI) findings of SABM, known as the “flip-flop” phenomenon, were observed in both the irradiated and nonirradiated areas, a finding previously unreported in the literature. The report highlighted the characteristic features of SABM in various MRI sequences, which can be easily misinterpreted as technical errors, leading to unnecessary repetition of MRIs.

In chronic heart failure (CHF) patients malnutrition and/or cachexia are frequently observed syndromes that negatively affect the quality of life and survival of patients. That makes it necessary to investigate reliable methods of assessment of body composition which can facilitate appropriate clinical decisions on patients’ treatment. Bioelectrical impedance analysis (BIA) is a reliable and non-invasive method to test body composition in patients suffering from various chronic diseases, including CHF. The aim of the review was to summarize recent findings on BIA assessment for nutritional and clinical management of CHF. Although BIA is a known technique used for body composition assessment, the number of papers analyzing its utility in cardiovascular diseases is still limited, particularly with a combination of molecular markers. Electrical parameters obtained in BIA in conjunction with biochemical determinations and molecular factors can improve selection of patients at risk of malnutrition and unfavorable prognosis related to nutritional deficits.

Abstract Background Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia. Methods This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan–Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL). Results C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28–1.80, P

In a recent article titled ''Embracing Cancer Complexity: Hallmarks of Systemic Disease'' published in Cell, Swaton et al. propose the idea of cancer as a guest that develops within a host. They discuss the possible causes and events of neoplastic cell dysregulations within an organism, highlighting events such as cachexia and thrombosis. However, we believe that to understand cancer-associated phenomena better, cancer cannot be considered a guest. In reality, cancer is born, develops, and spreads within its environment. It does not come from outside but instead uses the same system in which it lives to promote its death plan. Indeed, today we know that cancer not only causes local symptoms in the affected organ but also leads to systemic symptoms, which are evidence of inflammation associated with cancer. Inflammation is vital in controlling oncogenesis and neoplastic proliferation during the resistance phase, which is a critical moment for the immune system to demonstrate its effectiveness. However, if the immune system causes immunopathological damage, it may lead to necrosis and eventually to the tolerance phase, which can result in systemic symptoms. Understanding these phenomena thoroughly explains thrombophilia, anemia, sarcopenia, and iron metabolism disruption in advanced-stage neoplastic patients. The concept of the microenvironment takes on a different meaning in this context. The same cells that should oppose cancer in the tolerance phase now participate in a process that self-maintains, favoring the growth of the cancer and its death plan. The exact knowledge of these mechanisms is a more modern translational approach to treating cancer and its related symptoms.

Cachexia is a complicated metabolic syndrome mainly associated with cancers, characterized by extreme weight loss and muscle wasting. It is a debilitating condition that negatively affects prognosis and survival. However, there is currently no effective pharmacological intervention that can reverse body weight loss and improve physical performance in patients with cachexia. Growth differentiation factor 15 (GDF15) can suppress appetite and regulate energy balance through binding to glial cell-derived neurotrophic factor receptor alpha-like (GFRAL). In order to develop a novel, effective treatment for cachexia, we generated a GDF15-targeting VHH nanobody, GB18–06, that was able to bind GDF15 with high affinity. In vitro, GB18–06 potently inhibited the GDF15-GFRAL signaling pathway, leading to a reduction of downstream ERK and AKT phosphorylation levels; in vivo, GB18–06 alleviated weight loss (>20%) in cancer and chemotherapy-induced cachexia models in mice. Compared with the control (phosphate-buffered saline) group, the ambulatory activity of mice in the GB18–06-treated group also increased 77%. Furthermore, GB18–06 exhibited desirable pharmacokinetic properties and an excellent developability profile. Our study has demonstrated a means of developing targeted treatment for cachexia with high efficacy, potentially leading to improved clinical outcomes and quality of life for patients with cachexia.

Background: Chronic kidney disease is common, affecting up to 13 % of the global population, and is predicted to become the fifth leading cause of 'life years lost' by 2040. Individuals with end-stage kidney disease commonly develop complications such as protein-energy wasting and cachexia which further worsens their prognosis. The syndrome of ‘renal cachexia’ is poorly understood, under-diagnosed and even if recognised has limited treatment options. Objective: To explore the lived experience of renal cachexia for individuals with end-stage kidney disease and the interrelated experiences of their carers. Design: This interpretive phenomenological study was designed to facilitate an in-depth exploration of how patients and carers experience of renal cachexia. To improve and document the quality, transparency, and consistency of patient and public involvement in this study the Guidance for Reporting Involvement of Patients and the Public-Short Format was followed. Setting: The study was conducted across two nephrology directorates, within two healthcare trusts in the United Kingdom. Participants: Seven participants who met the inclusion criteria were recruited for this study, four patients (three female, one male) and three carers (two male, one female). Methods: We employed a purposive sampling strategy. Data collection was conducted between July 2022 and December 2023. Interviews were semi-structured, audio-recorded, transcribed verbatim and analysed in six steps by two researchers using interpretive phenomenological analysis. Ethical approval was approved by the Office for Research Ethics Committees Northern Ireland (Reference: 22/NI/0107). Results: Analysis generated six group experiential themes: the lived experience of appetite loss, functional decline and temporal coping, weight loss a visual metaphor of concern, social withdrawal and vulnerability, the emotional toll of eating challenges and psychological strain amidst a lack of information about cachexia. Conclusion: This is the first qualitative study exploring the lived experience of renal cachexia for patients and carers. Our study highlights that psycho-social and educational support is urgently needed. Additionally, healthcare professionals need better information provision to help them to recognise and respond to the needs of this population. Further research is required to develop models of holistic support which could help patients and carers cope with the impact of renal cachexia and optimally manage this syndrome within the family unit. Registration: N/A.

Cancer-associated cachexia (CAC) is a critical contributor to pancreatic ductal adenocarcinoma (PDAC) mortality. Thus, there is an urgent need for new strategies to mitigate PDAC-associated cachexia; and the exploration of dietary interventions is a critical component. We previously observed that a ketogenic diet (KD) combined with gemcitabine enhances overall survival in the autochthonous LSL-KrasG12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. In this study, we investigated the effect and cellular mechanisms of a KD in combination with gemcitabine on the maintenance of skeletal muscle mass in KPC mice. For this purpose, male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD), a KD, a CD + gemcitabine (CG), or a KD + gemcitabine (KG) group. We observed that a KD or a KG-mitigated muscle strength declined over time and presented higher gastrocnemius weights compared CD-fed mice. Mechanistically, we observed sex-dependent effects of KG treatment, including the inhibition of autophagy, and increased phosphorylation levels of eIF2α in KG-treated KPC mice when compared to CG-treated mice. Our data suggest that a KG results in preservation of skeletal muscle mass. Additional research is warranted to explore whether this diet-treatment combination can be clinically effective in combating CAC in PDAC patients.

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Pancreatic cancer is difficult to diagnose early and progresses rapidly. Researchers have found that a cytokine called Interleukin-6 (IL-6) is involved in the entire course of pancreatic cancer, promoting its occurrence and development. From the earliest stages of pancreatic intraepithelial neoplasia to the invasion and metastasis of pancreatic cancer cells and the appearance of tumor cachexia, IL-6 drives oncogenic signal transduction pathways and immune escape that accelerate disease progression. IL-6 is considered a biomarker for pancreatic cancer diagnosis and prognosis, as well as a potential target for treatment. IL-6 antibodies are currently being explored as a hot topic in oncology. This article aims to systematically explain how IL-6 induces the deterioration of normal pancreatic cells, with the goal of finding a breakthrough in pancreatic cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Cancer cachexia (CC) is a debilitating syndrome that affects 50–80% of cancer patients, varying in incidence by cancer type and significantly diminishing their quality of life. This multifactorial syndrome is characterized by muscle and fat loss, systemic inflammation, and metabolic imbalance. Extracellular vesicles (EVs), including exosomes and microvesicles, play a crucial role in the progression of CC. These vesicles, produced by cancer cells and others within the tumor environment, facilitate intercellular communication by transferring proteins, lipids, and nucleic acids. A comprehensive review of the literature from databases such as PubMed, Scopus, and Web of Science reveals insights into the formation, release, and uptake of EVs in CC, underscoring their potential as diagnostic and prognostic biomarkers. The review also explores therapeutic strategies targeting EVs, which include modifying their release and content, utilizing them for drug delivery, genetically altering their contents, and inhibiting key cachexia pathways. Understanding the role of EVs in CC opens new avenues for diagnostic and therapeutic approaches, potentially mitigating the syndrome's impact on patient survival and quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cachexia (CC) is a syndrome affecting advanced cancer patients, causing inflammation, metabolic dysfunction, and a decline in quality of life. It increases the risk of mortality. Nutritional therapies are being tested for improving muscle metabolism in cancer patients, but no special therapies have been validated in clinical practice. Studies suggest increasing muscle protein synthesis through amino acids or protein intake, and physical activity can reduce muscle atrophy. This manuscript provides an overview of the preclinical and clinical approaches for the use of amino acids with and without exercise therapy to improve muscle metabolism in cachexia. Cancer cachexia is a multifaceted syndrome that impacts individuals with advanced cancer. It causes numerous pathological changes in cancer patients, such as inflammation and metabolic dysfunction, which further diminish their quality of life. Unfortunately, cancer cachexia also increases the risk of mortality in affected individuals, making it an important area of focus for cancer research and treatment. Several potential nutritional therapies are being tested in preclinical and clinical models for their efficacy in improving muscle metabolism in cancer patients. Despite promising results, no special nutritional therapies have yet been validated in clinical practice. Multiple studies provide evidence of the benefits of increasing muscle protein synthesis through an increased intake of amino acids or protein. There is also increasing evidence that exercise can reduce muscle atrophy by modulating protein synthesis. Therefore, the combination of protein intake and exercise may be more effective in improving cancer cachexia. This review provides an overview of the preclinical and clinical approaches for the use of amino acids with and without exercise therapy to improve muscle metabolism in cachexia. [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.

• Targeting xCT in the tumor is mandatory to reduce tumor size. • Deleting xCT only in the host reduces tumor-induced inflammation and immunosuppressive Treg population. • Targeting xCT on the tumor attenuates hypothalamic inflammation. • Targeting xCT in the host reduces mood disturbances in tumor-bearing mice. • Immune xCT deletion has no benefit in tumor-bearing mice. xCT (Slc7a11), the specific subunit of the cystine/glutamate antiporter system x c -, is present in the brain and on immune cells, where it is known to modulate behavior and inflammatory responses. In a variety of cancers -including pancreatic ductal adenocarcinoma (PDAC)-, xCT is upregulated by tumor cells to support their growth and spread. Therefore, we studied the impact of xCT deletion in pancreatic tumor cells (Panc02) and/or the host (xCT-/- mice) on tumor burden, inflammation, cachexia and mood disturbances. Deletion of xCT in the tumor strongly reduced tumor growth. Targeting xCT in the host and not the tumor resulted only in a partial reduction of tumor burden, while it did attenuate tumor-related systemic inflammation and prevented an increase in immunosuppressive regulatory T cells. The latter effect could be replicated by specific xCT deletion in immune cells. xCT deletion in the host or the tumor differentially modulated neuroinflammation. When mice were grafted with xCT-deleted tumor cells, hypothalamic inflammation was reduced and, accordingly, food intake improved. Tumor bearing xCT-/- mice showed a trend of reduced hippocampal neuroinflammation with less anxiety- and depressive-like behavior. Taken together, targeting xCT may have beneficial effects on pancreatic cancer-related comorbidities, beyond reducing tumor burden. The search for novel and specific xCT inhibitors is warranted as they may represent a holistic therapy in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objective: The objective of this paper was to provide an understanding of cachexia in relation to oral squamous cell carcinoma relevant to oral health care. The paper is a scoping review of aspects of the clinical presentation, aetiology and management of cachexia in relation to oral health and oral health care. Methods: A combined search of MEDLINE and EMBASE databases (via OVID) was conducted using the terms ([Head and Neck] OR [Oral Squamous Cell Carcinoma]) AND (Cachexia). Duplicates were removed and results were subsequently limited to studies published between 2000 and 2023, humans and English language. After screening and full‐text assessment a total number of 87 studies were included in the review. Results: It is evident that cachexia is a not uncommon feature of patients with advanced malignancy of the head and neck driven by a multitude of mechanisms, induced by the tumour itself, that lead to reduced nutritional intake, increased metabolism and loss of adipose and skeletal tissue. Conclusion: While a variety of nutritional, physical, psychological and pharmacological interventions may improve quality and duration of life, ultimately the diagnosis of cachexia in relation to head and neck cancer remains an indicator of poor life expectancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated cachexia (CAC) is a serious condition wherein people with cancer lose muscle and fat, even with proper nutrition. It leads to weakness and can make treatment less effective. This review looks at how the body's immune system and certain proteins affect CAC. Studies show that specific proteins, like IL-6 and TNF-α, play a crucial role in causing muscle and fat loss. Other cells in the immune system, called MDSCs, make CAC worse by causing inflammation. Clinical studies also found high levels of certain proteins in people with CAC. Understanding these processes might improve treatments, especially for those undergoing immunotherapy. A new drug called R-ketorolac has shown promise in reversing weight loss in animals. Combining drugs like this with immunotherapy could help patients with cancer suffering from CAC. However, more research is needed to fully understand how immune problems and CAC interact during treatment. Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that is unresponsive to nutritional support and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like the neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed the weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cachexia (CC) is a complex syndrome requiring a multimodal approach. Although a universally accepted definition and staging criteria for cancer cachexia remains elusive, there is general consensus regarding the importance of elements such as weight loss, muscle wasting, and poor appetite. Epidemic trends of obesity and overlapping conditions such as sarcopenia and frailty further complicate CC definition, staging, and relevant outcome measures. Despite progress in understanding the molecular mechanisms of CC, there is no single, consistently effective pharmacotherapy for CC and, unsurprisingly, there are variations among guidelines regarding management. Current pharmacologic research is focused on promising targeted treatments; however, a multimodal approach is likely to be more effective than any single therapeutic agent. This narrative review provides an update on non-pharmacologic and pharmacologic treatment and proposes a theoretical model for management of CC, which includes a multimodal therapeutic approach directed at the various mechanisms contributing to CC. Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition. [ABSTRACT FROM AUTHOR]

Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system. [ABSTRACT FROM AUTHOR]

In our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA's direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice. The continuous infusion of Ang II resulted in the loss of the normal functions of the left ventricle (LV) (both systolic and diastolic), including a significant reduction in fractional shortening, an increase in heart weight and LV wall thickness, and the development of cardiac hypertrophy. The infusion of Ang II also resulted in the development of cardiac fibrosis, and significant increases in the expression levels of genes (ANP, BNP, and MHCβ) associated with cardiac hypertrophy and the chemical staining of the collagen abundance as an indication of fibrosis. In addition, Ang II caused a significant increase in expression levels of inflammatory cytokines (IL-6, IL-17, MIP-2, and IFNγ), NLRP3 inflammasomes, AT1 receptor, and a decrease in AT2 receptor. Treatment with WFA rescued the LV functions and heart hypertrophy and fibrosis. Our results demonstrated, for the first time, that, while WFA has anti-tumorigenic properties, it also ameliorates the cardiac dysfunction induced by Ang II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles. [ABSTRACT FROM AUTHOR]

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]

Background: Bronchiectasis is a chronic lung disease characterized by permanent bronchial wall dilatation. Although it has been known as an orphan disease, it has recently gained attention because of registry-based studies and drug research. Aims: We aimed to use a multicenter database to analyze and compare data regarding the etiology, associated comorbidities, microbiological characteristics, and preventive strategies of bronchiectasis in Türkiye to those of other countries. Study Design: A multicenter prospective cohort study. Methods: The multicenter, prospective cohort study was conducted between March 2019 and January 2022 using the Turkish Adult Bronchiectasis Database, in which 25 centers in Türkiye participated. Patients aged > 18 years who presented with respiratory symptoms such as cough, sputum, and dyspnea and were diagnosed with non-cystic fibrosis bronchiectasis using computed tomography were included in the study. Demographic information, etiologies, comorbidities, pulmonary functions, and microbiological, radiological, and clinical data were collected from the patients. Results: Of the 1,035 study participants, 518 (50%) were females. The mean age of the patients was 56.1 ± 16.1 years. The underlying etiology was detected in 565 (54.6%) patients. While postinfectious origin was the most common cause of bronchiectasis (39.5%), tuberculosis was identified in 11.3% of the patients. An additional comorbidity was detected in 688 (66.5%) patients. The most common comorbidity was cardiovascular disease, and chronic obstructive pulmonary disease (COPD) and bronchiectasis was identified in 19.5% of the patients. The most commonly detected microbiological agent was Pseudomonas aeruginosa (29.4%). Inhaled corticosteroids (ICS) were used in 70.1% of the patients, and the frequency of exacerbations in the last year was significantly higher in patients using ICS than in nonusers (p < 0.0001). Age [odds ratio (OR): 1.028; 95% confidence interval (CI): 1.005-1.051], cachexia (OR: 4.774; 95% CI: 2,054-11,097), high modified medical research [ABSTRACT FROM AUTHOR]

Background: Anamorelin was approved in Japan in 2021 to treat cancer cachexia associated with non‐small cell lung, gastric, pancreatic, or colorectal cancers. Post‐marketing surveillance is being conducted to evaluate the real‐world safety and effectiveness of anamorelin. Methods: This prospective, observational surveillance registered all patients who started treatment with anamorelin after April 21, 2021. Hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were defined as main safety specifications. Body weight (BW) and appetite were assessed as effectiveness specifications. Results: This analysis was based on data as of January 21, 2023. The safety and effectiveness analysis sets included 6016 and 4511 patients, respectively. Treatment‐related adverse events in ≥1% of patients were hyperglycemia (3.9%) and nausea (2.6%). The incidences of hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were 4.8%, 1.2%, and 1.1%, respectively. The mean changes (standard error [SE]) in BW from baseline to weeks 3, 12, 24, and 52 were 0.64 (0.05) kg, 1.19 (0.12) kg, 1.40 (0.21) kg, and 1.42 (0.39) kg, respectively. The mean changes (SE) in Functional Assessment of Anorexia/Cachexia Treatment 5‐item Anorexia Symptom Scale total scores from baseline to weeks 3, 12, 24, and 52 were 3.2 (0.09), 4.8 (0.18), 5.2 (0.30), and 5.3 (0.47), respectively, exceeding the clinically meaningful improvement score (2.0 points). Conclusion: The overall safety of anamorelin raised no new safety concerns, although continued caution may be required for hyperglycemia and nausea. Improvements in BW and appetite were also observed in real‐world clinical settings. [ABSTRACT FROM AUTHOR]

Oleocanthal (OC) is a monophenol of extra-virgin olive oil (EVOO) endowed with antibiotic, cardioprotective and anticancer effects, among others, mainly in view of its antioxidant and anti-inflammatory properties. OC has been largely investigated in terms of its anticancer activity, in Alzheimer disease and in collagen-induced arthritis; however, the possibility that it can also affect muscle biology has been totally overlooked so far. This study is the first to describe that OC modulates alterations induced in C2C12 myotubes by stimuli known to induce muscle wasting in vivo, namely TNF-α, or in the medium conditioned by the C26 cachexia-inducing tumor (CM-C26). C2C12 myotubes were exposed to CM-C26 or TNF-α in the presence or absence of OC for 24 and 48 h and analyzed by immunofluorescence and Western blotting. In combination with TNF-α or CM-C26, OC was revealed to be able to restore both the myotube's original size and morphology and normal levels of both atrogin-1 and MuRF1. OC seems unable to impinge on the autophagic–lysosomal proteolytic system or protein synthesis. Modulations towards normal levels of the expression of molecules involved in myogenesis, such as Pax7, myogenin and MyHC, were also observed in the myotube cultures exposed to OC and TNF-α or CM-C26. In conclusion, the data presented here show that OC exerts a protective action in C2C12 myotubes exposed to TNF-α or CM-C26, with mechanisms likely involving the downregulation of ubiquitin–proteasome-dependent proteolysis and the partial relief of myogenic differentiation impairment. [ABSTRACT FROM AUTHOR]

Cancer-related cachexia is a metabolic syndrome characterized by weight loss, adipose tissue decomposition, and progressive skeletal muscle atrophy. It is a major complication of many advanced cancers and seriously affects the quality of life and survival of cancer patients. However, the specific molecules that mediate cancer-related cachexia remain elusive, and the fundamental cellular and molecular mechanisms associated with muscle atrophy and lipidolysis in cancer patients still need to be investigated. Exosomes, a newly discovered class of small extracellular vesicles that facilitate intercellular communication, have a significant role in the onset and development of various cancers. Studies have shown that exosomes play a role in the onset and progression of cancer-related cachexia by transporting active molecules such as nucleic acids and proteins. This review aimed to provide an overview of exosome developments in cancer-induced skeletal muscle atrophy and adipose tissue degradation. More importantly, exosomes were shown to have potential as diagnostic markers or therapeutic strategies for cachexia and were prospected, providing novel strategies for the diagnosis and treatment of cancer-related cachexia. [ABSTRACT FROM AUTHOR]

While the excessive inflammation in cancer cachexia is well-known to be induced by the overproduction of inflammatory mediators in the periphery, microflora disruption and brain dysfunction are also considered to contribute to the induction of cancer cachexia. Hypothalamic microglia play a crucial role in brain inflammation and central-peripheral immune circuits via the production of inflammatory mediators. In the present study, we evaluated possible changes in excessive secretion of gut microbiota-derived endotoxin and the expression timeline of several inflammation-regulatory mediators and their inhibiting modulators in hypothalamic microglia of a mouse model of cancer cachexia following transplantation of pancreatic cancer cells. We demonstrated that the plasma level of lipopolysaccharide (LPS) was significantly increased with an increase in anaerobic bacteria, especially Firmicutes, in the gut at the late stage of tumor-bearing mice that exhibited dramatic appetite loss, sarcopenia and severe peripheral immune suppression. At the early stage, in which tumor-bearing mice had not yet displayed "cachexia symptoms", the mRNA expression of pro-inflammatory cytokines, but not of the neurodegenerative and severe inflammatory modulator lipocalin-2 (LCN2), was significantly increased, whereas at the late "cachexia stage", the level of LCN2 mRNA was significantly increased along with significant decreases in levels of inhibitory immune checkpoint receptors programmed death receptor-1 (PD-1) and CD112R in hypothalamic microglia. In addition, a high density of activated neurons in the paraventricular nucleus (PVN) of the hypothalamus region and a significant increase in corticosterone secretion were found in cachexia model mice. Related to the cachexia state, released corticosterone was clearly increased in normal mice with specific activation of PVN neurons. A marked decrease in the natural killer cell population was also observed in the spleen of mice with robust activation of PVN neurons as well as mice with cancer cachexia. On the other hand, in vivo administration of LPS in normal mice induced hypothalamic microglia with low expression of inhibitory immune checkpoint receptors. These findings suggest that the induction of cancer cachexia may parallel exacerbation of the hypothalamic inflammatory status with polarization to microglia expressed with low levels of inhibitory immune checkpoint receptors following LPS release from the gut microflora. [ABSTRACT FROM AUTHOR]

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty. [ABSTRACT FROM AUTHOR]

Chemotherapy is a major contributor to cachexia, but studies often investigate male animals. Here, we investigated whether sex modifies the effects of chemotherapy on cachexia and BCAA metabolism. Ten‐week‐old CD2F1 male and female mice were treated with the chemotherapy drug cocktail folfiri (50 mg/kg 5‐fluorouracil, 90 mg/kg leucovorin, and 24 mg/kg CPT11) (drug) or vehicle twice a week for 6 weeks. Insulin tolerance tests were conducted and BCAA levels and metabolism were measured in plasma and tissues. Drug treatment reduced body and skeletal muscle weights and anabolic signaling in both sexes, with females showing worsened outcomes (p < 0.05 for all). Drug treatment increased plasma BCAA only in males, but BCAA concentrations in the skeletal muscle of both sexes were decreased; this decrease was more profound in males (p = 0.0097). In addition, muscle expression of the BCAA transporter LAT1 was reduced; this reduction was more severe in females (p = 0.0264). In both sexes, the (inhibitory) phosphorylation of BCKD‐E1αser293 was increased along with decreased BCKD activity. In the liver, drug treatment increased BCAA concentrations and LAT1 expression, but BCKD activity was suppressed in both sexes (p < 0.05 for all). Our results demonstrate that altered BCAA metabolism may contribute to chemotherapy‐induced cachexia in a sex‐dependent manner. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study examined how muscle function is affected in cancer patients, particularly those at risk of developing muscle wasting (cachexia). We tested a combination of mild exercise and a protein-rich diet as a potential preventive measure. By analysing muscle fibres from patients undergoing different treatments, we found that cancer cachexia leads to muscle weakness and stiffness. However, our results show that the combined therapy helps maintain muscle flexibility and function. This suggests that such an intervention could improve the quality of life for cancer patients by preserving muscle health. Patients with aggressive cancer, e.g., gastrointestinal cancer, are prone (≥50% chance) to developing cancer cachexia (CC). Little is known about the effects of CC on the biomechanical function of muscle. A promising prevention strategy was found in the form of a multi-modal therapy combining mild resistance exercise (e.g., whole-body electro-myostimulation, WB-EMS) and a protein-rich diet. In a previous study of ours, this was effective in counteracting the loss of muscle mass, yet a systematic and comprehensive assessment of active and passive single muscle fibre functions was so far absent. This pilot study investigated the biomechanical function of single muscle fibres (rectus abdominis) from the biopsies of conventionally treated (pre-)cachectic cancer ((pre-)CC) patients (m = 9), those receiving the multi-modal therapy comprising WB-EMS training and protein-rich nutrition (m = 3), and a control group (m = 5). Our findings not only align with previous findings showing the absolute force loss in CC that is accelerated by atrophy but also speak in favour of a different, potentially energy- and Ca2+-homeostasis-related effect that compromises muscle contraction (F ~0.9 mN vs. F ~0.6 mN in control patients). However, myofibrillar Ca2+ sensitivity and the quality of contraction were unaltered (pCa50: 5.6–5.8). Single fibres from the (pre-)CC patients receiving WB-EMS training and protein supplementation were significantly more compliant (p < 0.001 at ≥130% of resting length L0). Those fibres displayed a similar softness to the ones from the control patients (axial compliance ~15 m/N at ≥130% L0), while single fibres from the patients with (developing) cachexia were significantly stiffer (axial compliance ~7 m/N, p < 0.001 at ≥130% L0). Adjuvant multi-modal therapy (WB-EMS training and nutritional support) contributes to maintaining the axial compliance of single fibres and potentially improves the quality of life for patients at risk of developing CC. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder with systemic consequences that can cause a muscle loss phenotype (MLP), which is characterized by the loss of muscle mass, muscle strength, or loss of both muscle and fat mass. There are limited data comparing the individual traits of MLP with clinical outcomes in a large unbiased cohort of COPD patients. Our aim was to determine the proportion of patients who met criteria for MLP in an unbiased sample of COPD patients at the population-level. We also determined if specific MLP features were associated with all-cause and COPD-related mortality. Methods: A retrospective population-based cohort analysis of the UK Biobank was performed. COPD was defined by a FEV1/FVC ratio < 0.7, physician established diagnosis of COPD, or those with a COPD-related hospitalization before baseline assessment. MLP included one or more of the following: 1) Low fat-free mass index (FFMI) on bioelectric impedance analysis (BIA) or 2) Appendicular skeletal muscle index (ASMI) on BIA, 3) Low muscle strength defined by handgrip strength (HGS), or 4) Low muscle and fat mass based on body mass index (BMI). Cox regression was used to determine the association between MLP and all-cause or COPD-related mortality. All models were adjusted for sex, age at assessment, ethnicity, BMI, alcohol use, smoking status, prior cancer diagnosis and FEV1/FVC ratio. Results: There were 55,782 subjects (56% male) with COPD followed for a median of 70.1 months with a mean(± SD) age at assessment of 59 ± 7.5 years, and FEV1% of 79.2 ± 18.5. Most subjects had mild (50.4%) or moderate (42.8%) COPD. Many patients had evidence of a MLP, which was present in 53.4% of COPD patients (34% by ASMI, 26% by HGS). Of the 5,608 deaths in patients diagnosed with COPD, 907 were COPD-related. After multivariate adjustment, COPD subjects with MLP had a 30% higher hazard-ratio for all-cause death and 70% higher hazard-ratio for COPD-related death. Conclusions: Evidence of MLP is common in a large population-based cohort of COPD and is associated with higher risk for all-cause and COPD-related mortality. [ABSTRACT FROM AUTHOR]

(1) Background: Gastric cancer is a significant cause of cancer-related mortality worldwide. Weight loss and malnutrition associated with cancer are linked with increased mortality rates and reduced quality of life. Cancer cachexia, characterised by the loss of skeletal muscle, is associated with approximately 20% of cancer-related deaths and differs from malnutrition in that it cannot be fully reversed by nutritional support alone. It is now recognised that the primary pathophysiological process underlying cancer cachexia is chronic inflammation leading to increased calorie consumption. Current treatments that focus on nutritional supplementation, psychological counselling, appetite stimulation and reducing inflammation are lacking in efficacy. This review focuses on the evidence supporting the potential roles of natural anti-inflammatory products and their derivatives including fatty acids, probiotics, amino acids, curcumin, fucoidan, epigallocatechin-3-gallate, ginger, resveratrol and Boswellia serrata in the management of gastric cancer cachexia. (2) Results: While natural anti-inflammatory products show promise in a number of in vitro and in vivo studies, there are only a small number of human studies available. Where present, the evidence base is heterogeneous, with varying study methodologies and outcomes. (3) Conclusions: Natural anti-inflammatory products represent a potential adjunctive therapy for gastric cancer cachexia. Further research, particularly well-designed clinical trials, is needed to elucidate their optimal role, dosing and safety profiles in the management of gastric cancer cachexia. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a tumour-induced wasting syndrome, characterised by extreme loss of skeletal muscle. Defective mitochondria can contribute to muscle wasting; however, the underlying mechanisms remain unclear. Using a Drosophila larval model of cancer cachexia, we observed enlarged and dysfunctional muscle mitochondria. Morphological changes were accompanied by upregulation of beta-oxidation proteins and depletion of muscle glycogen and lipid stores. Muscle lipid stores were also decreased in Colon-26 adenocarcinoma mouse muscle samples, and expression of the beta-oxidation gene CPT1A was negatively associated with muscle quality in cachectic patients. Mechanistically, mitochondrial defects result from reduced muscle insulin signalling, downstream of tumour-secreted insulin growth factor binding protein (IGFBP) homologue ImpL2. Strikingly, muscle-specific inhibition of Forkhead box O (FOXO), mitochondrial fusion, or beta-oxidation in tumour-bearing animals preserved muscle integrity. Finally, dietary supplementation with nicotinamide or lipids, improved muscle health in tumour-bearing animals. Overall, our work demonstrates that muscle FOXO, mitochondria dynamics/beta-oxidation and lipid utilisation are key regulators of muscle wasting in cancer cachexia. Synopsis: In a Drosophila larval eye imaginal disc tumour model of cancer cachexia, this study demonstrates that muscle FOXO, mitochondria dynamics/beta-oxidation and lipid utilisation are key regulators of muscle wasting. Downstream of FOXO, mitochondrial fusion and beta-oxidation are responsible for increased utilisation of muscle lipids, causing loss of muscle integrity. Feeding cachectic flies a diet supplemented with nicotinamide (Vitamin B3), or a high-fat coconut oil diet, which replenished lipids in the muscle, were sufficient to improve muscle integrity. A similar depletion of lipid reserves is observed in muscles of the C-26 mouse cachexia model. Beta-oxidation gene Carnitine palmitoyltransferase 1A (CPT1A, the mammalian homolog of Whd) is negatively correlated with muscle quality in cachectic patients with pancreatic ductal adenocarcinoma. In a Drosophila larval eye imaginal disc tumour model of cancer cachexia, this study demonstrates that muscle FOXO, mitochondria dynamics/beta-oxidation and lipid utilisation are key regulators of muscle wasting. [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: Pancreatic ductal adenocarcinoma (PDAC) presents with a high mortality rate. Two important features of PDAC contribute to this poor outcome. The first is metastasis which occurs in ~ 80% of PDAC patients. The second is cachexia, which compromises treatment tolerance for patients and reduces their quality of life. Although various mouse models of PDAC exist, recapitulating both metastatic and cachectic features have been challenging. Methods: Here, we optimize an orthotopic mouse model of PDAC by altering several conditions, including the subcloning of parental murine PDAC cells, implantation site, number of transplanted cells, and age of recipient mice. We perform spatial profiling to compare primary and metastatic immune microenvironments and RNA sequencing to gain insight into the mechanisms of muscle wasting in PDAC-induced cachexia, comparing non-metastatic to metastatic conditions. Results: These modifications extend the time course of the disease and concurrently increase the rate of metastasis to approximately 70%. Furthermore, reliable cachexia endpoints are achieved in both PDAC mice with and without metastases, which is reminiscent of patients. We also find that cachectic muscles from PDAC mice with metastasis exhibit a similar transcriptional profile to muscles derived from mice and patients without metastasis. Conclusion: Together, this model is likely to be advantageous in both advancing our understanding of the mechanism of PDAC cachexia, as well as in the evaluation of novel therapeutics. [ABSTRACT FROM AUTHOR]

Cancer therapy seeks to restrain malignant cell growth, with the majority of dietary interventions targeting a reduction of cachexia, a condition linked to poor prognosis. However, recent research suggests these methods are outdated in certain cancer types, where weight stability or gain may occur during treatment. Integration of complementary approaches such as fasting, fasting mimicking diets (FMDs, also known as caloric restriction (CR)), and time-restricted feeding (TRF) into cancer treatment strategies is gaining attention for potentially enhancing chemotherapy efficacy while reducing adverse effects. This overview evaluates existing literature on ongoing clinical trials, animal studies and potential fasting benefits, clinical applications, and research gaps regarding chemotherapy outcomes and quality of life (QoL). Fasting triggers differential stress resistance (DSR) and shields normal cells while sensitising cancer cells to chemotherapy, and protecting cells from chemotherapy toxicity while enhancing QoL, and potentially prognosis. Fasting modulates blood glucose levels, oxidative stress, tumour expansion, and inflammation, and promotes autophagy, underpinning the focus on adopting fasting along with traditional medical intervention. It is agreed that if this line of therapy is adopted it is vital that clinical team involvement is sought to assess patient suitability, safety, and compatibility with chemotherapy, particularly in cachexic patients. Further research in human studies is required to validate fasting's benefits and to establish reliable endpoints. [ABSTRACT FROM AUTHOR]

End of life care in dementia is important to avoid patients receiving unnecessary investigations and treatments. In this paper, the authors discuss the final stage of dementia, illustrating this with a case example reflecting what is frequently encountered in hospital practice. The distinction is drawn between 'terminal inanition' of dementia and the more protracted cachexia, sarcopenia and progressive frailty that accompanies advancing dementia, with best practice clinical care considerations for palliative care outlined. [ABSTRACT FROM AUTHOR]

Simple Summary: Myelofibrosis is a rare bone marrow disorder, leading to an increasing failure to generate healthy blood cells. Defining clinical prognosis scores for rare diseases is difficult, as sufficient numbers of patients for score validation are difficult to obtain. The current study investigates the utility of the TriNetX database, containing electronic medical records for over 140 million patients, to identify risk factors and establish clinical scores. TriNetX includes more than 64,000 myelofibrosis patients, and the present study explores factors influencing survival and common complications. Age over 65, anemia, an increased number of leukocytes, a low platelet count and an increased number of monocytes are associated with increased risks, while high numbers of eosinophiles and basophiles show positive associations. We demonstrate that the TriNetX database offers insights to refine predictive models, crucial for tailoring treatments to individual patient risks in the complex landscape of rare diseases like myelofibrosis. Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. Despite progress in molecular understanding and treatment, the clinical and prognostic heterogeneity of MF complicates treatment decisions. The International Prognostic Scoring System (IPSS) integrates clinical factors for risk stratification in MF. This study leverages the TriNetX database with more than 64,000 MF patients to assess the impact of accessible parameters on survival and complicating events, including AML transformation, cachexia, increased systemic inflammation, thrombosis and hemorrhage. Age over 65 years correlated with increased risks of death, AML transformation, thrombosis and hemorrhage. Anemia (Hb < 10 g/dL), leukocytosis (>25 × 103/µL) and thrombocytopenia (<150 × 103/µL) reduced survival and increased risks across all assessed events. Monocytosis is associated with decreased survival, whereas eosinophilia and basophilia were linked to improved survival. Further, as proof of concept for the applicability of TriNetX for clinical scores, we devised a simplified IPSS, and confirmed its value in predicting outcomes. This comprehensive study underscores the importance of age, anemia, leukocytosis and thrombocytopenia in predicting disease trajectory and contributes to refining prognostic models, addressing the challenges posed by the disease's heterogeneity. [ABSTRACT FROM AUTHOR]

Simple Summary: Symptom management in the cancer setting focuses on the improvement of the overall quality of life and physical function, particularly for patients with muscle and weight loss, a syndrome known as cachexia, who suffer from low functional ability. Yet, there are no guidelines for measuring or defining low functional ability or standards for identifying meaningful changes in functional ability in response to disease and/or treatment. This unmet need is a major obstacle to developing new/improved therapies for cancer cachexia. This review presents the available evidence for identifying low functional ability and meaningful changes in functional ability in patients with cancer cachexia. Patients with cachexia may display a meaningful reduction in hand grip strength, which may be improved by interventions aiming to increase muscle mass. Future studies should confirm these observations in addition to identifying low functional ability and meaningful changes for other functional outcomes. Managing clinical manifestations of cancer/treatment burden on functional status and quality of life remains paramount across the cancer trajectory, particularly for patients with cachexia who display reduced functional capacity. However, clinically relevant criteria for classifying functional impairment at a single point in time or for classifying meaningful functional changes subsequent to disease and/or treatment progression are lacking. This unmet clinical need remains a major obstacle to the development of therapies for cancer cachexia. This review aims to describe current literature-based evidence for clinically meaningful criteria for (1) functional impairment at a single timepoint between cancer patients with or without cachexia and (2) changes in physical function over time across interventional studies conducted in patients with cancer cachexia. The most common functional assessment in cross-sectional and interventional studies was hand grip strength (HGS). We observed suggestive evidence that an HGS deficit between 3 and 6 kg in cancer cachexia may display clinical relevance. In interventional studies, we observed that long-duration multimodal therapies with a focus on skeletal muscle may benefit HGS in patients with considerable weight loss. Future studies should derive cohort-specific clinically relevant criteria to confirm these observations in addition to other functional outcomes and investigate appropriate patient-reported anchors. [ABSTRACT FROM AUTHOR]