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BACKGROUND: Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence-based approaches are urgently needed to optimize treatment. METHODS: A systematic review and network meta-analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model. RESULTS: Seven placebo-controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83-8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73-6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84-2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42-2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07-0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30-2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42-1.88). However, network meta-analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety. CONCLUSION: Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.
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Caquexia , Neoplasias , Metaanálisis en Red , Olanzapina , Caquexia/tratamiento farmacológico , Caquexia/etiología , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Olanzapina/uso terapéutico , Olanzapina/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Oligopéptidos/uso terapéutico , Oligopéptidos/efectos adversos , HidrazinasRESUMEN
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.
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Caquexia , Aprendizaje Automático , Neoplasias , Humanos , Caquexia/etiología , Caquexia/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias/complicaciones , Anciano , Estudios de Cohortes , Proteína C-Reactiva/análisis , AdultoRESUMEN
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.
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Caquexia , Monocitos , Músculo Esquelético , Neoplasias , Neutrófilos , Caquexia/metabolismo , Caquexia/etiología , Monocitos/metabolismo , Monocitos/inmunología , Humanos , Neoplasias/complicaciones , Neoplasias/metabolismo , Neoplasias/inmunología , Neutrófilos/metabolismo , Animales , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Ratones , Masculino , Transducción de Señal , Línea Celular Tumoral , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Ratones Endogámicos C57BL , Interleucinas/metabolismo , Interleucinas/genética , Femenino , Perfilación de la Expresión GénicaRESUMEN
OBJECTIVE: To evaluate the frequency of cachexia and its associated factors using the Asian Working Group for Cachexia (AWGC) criteria in elderly patients with diabetes and chronic diseases. METHODS: The subjects were diabetic outpatients of ≥65 years of age who were managed at Ise Red Cross Hospital. Patients with chronic disease (chronic heart failure, cancer, or chronic renal failure). Cachexia was evaluated based on the AWGC criteria and was defined as a body mass index (BMI) <21 kg/m2 and one or more of the following: anorexia, elevated C-reactive protein, and decreased grip strength. A logistic regression analysis was used to identify cachexia-related factors, with cachexia as the dependent variable, and various variables (basic attributes, blood glucose-related parameters, diabetic complications, comorbidities, and treatment) as explanatory variables. RESULTS: Two hundred forty-two patients (male, n=164; female, n=78) were included in the study. Forty patients (16.5%) had cachexia. A logistic analysis revealed that age (odds ratio (OR), 1.16; P<0.001), type 1 diabetes (OR, 15.25; P=0.002), diabetic retinopathy (OR, 5.72; P=0.001), and physical frailty (OR, 7.06; P<0.001) were associated with cachexia. CONCLUSION: Elderly diabetics with chronic diseases were more likely to have cachexia. According to the AWGC criteria, the frequency of cachexia was 16.5% in elderly patients with diabetes and chronic diseases. Additionally, type 1 diabetes, diabetic retinopathy, age, and physical frailty were identified as factors associated with cachexia. In elderly diabetes patients with chronic diseases, it is therefore important to raise awareness regarding cachexia when these related factors are diagnosed.
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Caquexia , Humanos , Caquexia/diagnóstico , Caquexia/etiología , Anciano , Masculino , Femenino , Enfermedad Crónica , Anciano de 80 o más Años , Diabetes Mellitus , Complicaciones de la DiabetesRESUMEN
INTRODUCTION: Heart failure (HF) is associated with significant alterations in body composition, including malnutrition due to insufficient intake, chronic inflammation and increased energy expenditure. Identifying the prevalence of malnutrition and the risk of sarcopenia in patients with HF is crucial to improve clinical outcomes. MATERIAL AND METHODS: This cross-sectional, single-center, observational study involved 121 outpatients diagnosed with HF. Nutritional status was assessed using the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), and the Subjective Global Rating (SGA). Sarcopenia was screened using the SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls) questionnaire and diagnosed based on the European Working Group in Older People (EWGSOP2) criteria and functionality with the Short Performance Battery (SPPB) test. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. RESULTS: The study found that 10.7% had cardiac cachexia and 45.4% of deceased patients had been in this condition (p = 0.002). Moderate-to-high risk of malnutrition was identified in 37.1%, 23.9%, and 31.4% of patients according to the MNA, MUST, and SGA tests, respectively. According to the GLIM criteria, 56.2% of patients were malnourished. Additionally, 24.8% of patients had a high probability of sarcopenia, and 57.8% were not autonomous according to SPPB. Patients with less than 30% quadriceps muscle contraction were at a high risk of sarcopenia. CONCLUSIONS: There is a high prevalence of malnutrition among outpatients with HF, which is associated with worse prognosis, increased risk of sarcopenia, and greater frailty. These findings underscore the importance of early nutritional and functional assessments in this population to improve clinical outcomes.
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Insuficiencia Cardíaca , Desnutrición , Evaluación Nutricional , Estado Nutricional , Pacientes Ambulatorios , Sarcopenia , Humanos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Anciano , Estudios Transversales , Desnutrición/epidemiología , Desnutrición/diagnóstico , Sarcopenia/epidemiología , Sarcopenia/diagnóstico , Pacientes Ambulatorios/estadística & datos numéricos , Prevalencia , Anciano de 80 o más Años , Persona de Mediana Edad , Caquexia/epidemiología , Caquexia/etiología , Composición CorporalRESUMEN
(1) Background: Impaired nutritional status in systemic sclerosis (SSc) is prevalent. (2) Objective: This study aimed to identify pre-cachexia and malnutrition in SSc patients and to estimate the effectiveness of a high-protein oral nutritional supplement (ONS) in improving their nutritional status. (3) Materials and methods: The SSc population comprised 56 patients and a control group of 49 healthy persons. After a baseline clinical evaluation, bioelectrical impedance analysis (BIA), and laboratory tests, SSc patients were divided into well-nourished, pre-cachectic, and malnourished categories. SSc patients with a nutritional disbalance received a high-protein ONS once daily for 3 months. Patients were reassessed at 3 and 12 months after inclusion in the study. (4) Results: SSc patients, in comparison to the control group, had a significantly lower seven-point SGA value [6(0) vs. 7(1), p < 0.001)], lean tissue mass [LTM, 35.1 (10.5) vs. 40.1 (10.10), p = 0.008], and lean tissue index [LTI, 13.5 (3) vs. 14.9 (4), p = 0.009]. Of the 56 SSc patients, 40 (71.4%) were well nourished, 5 (8.9%) had pre-cachexia, and 11 (19.7%) were malnourished. A high-protein ONS in the pre-cachexia group stabilized the SGA value, anthropometric measurements, and BIA after 3 and 12 months. In malnourished patients, it significantly improved the SGA value [5(0) vs. 6(0), p = 0.002], LTI [12.1 (2.1) vs. 12.7 (3.2), p = 0.021] and LTM [31.1 (7.7) vs. 35.1 (9.1), p = 0.021], and that effect remained stable at 12 months. (5) Conclusion: Malnutrition is a common complication of SSc that can be improved with nutritional intervention.
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Suplementos Dietéticos , Desnutrición , Estado Nutricional , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/dietoterapia , Femenino , Masculino , Persona de Mediana Edad , Desnutrición/etiología , Anciano , Composición Corporal , Adulto , Proteínas en la Dieta/administración & dosificación , Caquexia/etiología , Caquexia/dietoterapia , Caquexia/terapia , Impedancia Eléctrica , Dieta Rica en ProteínasRESUMEN
Drugs have actions that may be classified as therapeutic effects and side effects; side effects are actions that do not contribute to therapeutic benefit. Some side effects are neutral; others, experienced as undesirable or unpleasant, are recorded as adverse effects. Some drug actions are therapeutic for some disorders and adverse for others; or therapeutic during acute illness and adverse during maintenance treatment. As an example, anticholinergic action may be adverse when a tricyclic antidepressant is used to treat depression but therapeutic when the drug is used to treat irritable bowel syndrome with diarrhea. In clinical practice, side or adverse effects of a drug may be leveraged to manage troublesome symptoms. As an example, the sedative effect of a low dose of trazodone may be useful for some patients with insomnia. With this background, studies have examined whether the increase in appetite and weight associated with olanzapine and mirtazapine may be effective against anorexia and cachexia associated with cancer and cancer chemotherapy. The subject is important because cachexia may be present in 30%-50% of patients with cancer (with higher prevalence in patients with more advanced cancer) and because the presence of cachexia is associated with a higher risk of disease progression and mortality. Many randomized controlled trials (RCTs) have examined pharmacologic interventions such as progestins, corticosteroids, anamorelin, and medical cannabis for cancer related cachexia; most results have been disappointing. A recent RCT found that olanzapine (2.5 mg/d for 12 weeks) improved appetite, weight, other nutritional parameters, and quality of life in patients with locally advanced or metastatic cancer treated with chemotherapy. Another RCT, however, found that mirtazapine (30 mg/d for 8 weeks) brought no nutritional or anthropometric gain in patients with cancer and anorexia. It is concluded that olanzapine but not mirtazapine merits further investigation in patients with cancer who have anorexia and cachexia.
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Anorexia , Benzodiazepinas , Caquexia , Mianserina , Mirtazapina , Neoplasias , Olanzapina , Humanos , Mirtazapina/uso terapéutico , Mirtazapina/efectos adversos , Olanzapina/uso terapéutico , Olanzapina/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Anorexia/inducido químicamente , Anorexia/tratamiento farmacológico , Mianserina/análogos & derivados , Mianserina/efectos adversos , Mianserina/uso terapéutico , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Benzodiazepinas/farmacología , Caquexia/tratamiento farmacológico , Caquexia/etiología , Caquexia/inducido químicamente , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Antidepresivos Tricíclicos/efectos adversos , Antidepresivos Tricíclicos/uso terapéuticoRESUMEN
BACKGROUND: Cancer cachexia is characterized by the loss of body weight (BW) and anorexia. Anamorelin (ANAM) is a selective ghrelin receptor agonist with appetite-enhancing anabolic action. The ONO-7643-05 trial demonstrated that ANAM increased lean body mass and improved anorexia in a Japanese population. However, the clinical outcomes of patients on ANAM have not yet been reported. PATIENTS AND METHODS: We investigated the clinical outcomes of patients with unresectable, advanced, or recurrent gastrointestinal cancer (colorectal, gastric, or pancreatic cancer) who were treated with ANAM between April 2017 and August 2022. Cachexia was defined as the presence of anorexia and a loss of ≥ 5% of BW within 6 months. To evaluate the response to ANAM, the patients who had discontinued ANAM within 3 weeks were excluded. Response to ANAM was defined as maintenance of or increase in BW and improved appetite from baseline at every 3-week evaluation. We also collected data on the reasons for the discontinuation of ANAM and the correlation between clinical factors and ANAM response. Safety analysis of ANAM was performed for all patients who received ANAM. RESULTS: Seventy-four patients were included in this study (49 males and 25 females), with a median age of 67.1 years (range, 36-83). The primary tumors were colorectal cancer in 27 (36.5%), gastric cancer in 20 (27.0%), and pancreatic cancer in 27 (36.5%). The Eastern Cooperative Oncology Group performance status was 0 in 10 (13.5%), 1 in 44 (59.5%), and ≥ 2 in 20 (27.0%). The number of previous chemotherapy regimens was 0 in 20 (27.0%), 1 in 22 (29.7%), and ≥ 2 in 32 (43.2%). ANAM was discontinued within 3 weeks in 28 patients for the following reasons: low-grade (grade 1 or 2) adverse events in 15 patients, ileus in three, grade 3 fatigue in one, progressive disease in one, censored follow-up in six, and unknown reasons in three. The proportion of ANAM responders was 63.6% (95% confidence interval, 47.8-77.6%). Among baseline characteristics, age ≥ 75 attenuated the ANAM response (p = 0.03). ANAM responders showed better disease control with chemotherapy than non-responders (75.0% vs. 37.5%, p = 0.02). CONCLUSIONS: ANAM may improve the outcomes of patients with gastrointestinal cancer cachexia in clinical practice.
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Caquexia , Neoplasias Gastrointestinales , Humanos , Masculino , Caquexia/tratamiento farmacológico , Caquexia/etiología , Femenino , Anciano , Persona de Mediana Edad , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/tratamiento farmacológico , Anciano de 80 o más Años , Adulto , Oligopéptidos/uso terapéutico , Oligopéptidos/farmacología , Japón , HidrazinasRESUMEN
Oxidative stress contributes to the loss of skeletal muscle mass and function in cancer cachexia. However, this outcome may be mitigated by an improved endogenous antioxidant defence system. Here, using the well-established oxidative stress-inducing muscle atrophy model of Lewis lung carcinoma (LLC) in 13-week-old male C57BL/6J mice, we demonstrate that extracellular superoxide dismutase (EcSOD) levels increase in the cachexia-prone extensor digitorum longus muscle. LLC transplantation significantly increased interleukin-1ß (IL-1ß) expression and release from extensor digitorum longus muscle fibres. Moreover, IL-1ß treatment of C2C12 myotubes increased NBR1, p62 phosphorylation at Ser351, Nrf2 nuclear translocation and EcSOD protein expression. Additional studies in vivo indicated that intramuscular IL-1ß injection is sufficient to stimulate EcSOD expression, which is prevented by muscle-specific knockout of p62 and Nrf2 (i.e. in p62 skmKO and Nrf2 skmKO mice, respectively). Finally, since an increase in circulating IL-1ß may lead to unwanted outcomes, we demonstrate that targeting this pathway at p62 is sufficient to drive muscle EcSOD expression in an Nrf2-dependent manner. In summary, cancer cachexia increases EcSOD expression in extensor digitorum longus muscle via muscle-derived IL-1ß-induced upregulation of p62 phosphorylation and Nrf2 activation. These findings provide further mechanistic evidence for the therapeutic potential of p62 and Nrf2 to mitigate cancer cachexia-induced muscle atrophy. KEY POINTS: Oxidative stress plays an important role in muscle atrophy during cancer cachexia. EcSOD, which mitigates muscle loss during oxidative stress, is upregulated in 13-week-old male C57BL/6J mice of extensor digitorum longus muscles during cancer cachexia. Using mouse and cellular models, we demonstrate that cancer cachexia promotes muscle EcSOD protein expression via muscle-derived IL-1ß-dependent stimulation of the NBR1-p62-Nrf2 signalling pathway. These results provide further evidence for the potential therapeutic targeting of the NBR1-p62-Nrf2 signalling pathway downstream of IL-1ß to mitigate cancer cachexia-induced muscle atrophy.
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Caquexia , Interleucina-1beta , Ratones Endogámicos C57BL , Músculo Esquelético , Factor 2 Relacionado con NF-E2 , Transducción de Señal , Superóxido Dismutasa , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Caquexia/metabolismo , Caquexia/etiología , Caquexia/genética , Masculino , Interleucina-1beta/metabolismo , Músculo Esquelético/metabolismo , Ratones , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Proteína Sequestosoma-1/metabolismo , Proteína Sequestosoma-1/genética , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/complicaciones , Carcinoma Pulmonar de Lewis/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/etiología , Atrofia Muscular/genética , Ratones Noqueados , Estrés OxidativoRESUMEN
Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single-nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-dependent gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. Short hairpin RNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of muscle atrophy associated with cancer cachexia and highlight potential therapeutic targets for this disorder.
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Caquexia , Atrofia Muscular , Miogenina , Miostatina , Caquexia/patología , Caquexia/metabolismo , Caquexia/etiología , Animales , Atrofia Muscular/patología , Atrofia Muscular/metabolismo , Ratones , Miostatina/metabolismo , Miostatina/genética , Miogenina/metabolismo , Miogenina/genética , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Neoplasias/complicaciones , Neoplasias/patología , Neoplasias/metabolismo , Ratones Endogámicos C57BL , Masculino , Transducción de Señal , Folistatina/metabolismo , HumanosRESUMEN
BACKGROUND: Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. METHODS: We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. RESULTS: Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. CONCLUSION: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.
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Caquexia , Progresión de la Enfermedad , Ratones Endogámicos BALB C , Sistema Nervioso Simpático , Animales , Caquexia/metabolismo , Caquexia/patología , Caquexia/etiología , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatología , Masculino , Ratones , Proteína Desacopladora 1/metabolismo , Línea Celular Tumoral , Canales Iónicos/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Oxidopamina , Simpatectomía Química , Interleucina-6/metabolismo , Índice de Masa Corporal , Neoplasias/complicaciones , Neoplasias/patología , Neoplasias/metabolismoRESUMEN
Cachexia is associated with lower overall survival (OS) in patients with cancer; however, the relationship between the two is reported to differ according to the definitive criteria for diagnosing cachexia. We aimed to investigate 1) the difference in the prevalence of cachexia in patients with cancer and 2) the association between cachexia and OS, depending on the definitive criteria for diagnosing cachexia in patients with cancer. We searched PubMed and Web of Science from their inception until July 31, 2023, to identify eligible studies. We conducted a systematic review of the prevalence of cachexia in patients with cancer and performed a meta-analysis to investigate its relationship with OS. A total of 125 articles comprising 137,960 patients were included in the systematic review, and 26 articles consisting of 11,118 patients underwent meta-analysis. The overall prevalence of cachexia in patients with cancer was 33.0% (95% confidence interval [CI]: 32.8, 33.3); however, it varied according to the definitive criteria for diagnosing cachexia (13.9%-56.5%). According to the Fearon 2011 criteria, the prevalence of cachexia was associated with a high hazard ratio (HR) for OS compared with that of noncachexia [HR: 1.58 (95% CI: 1.45, 1.73)]; according to the other criteria, the HR was 2.78 (95% CI: 1.88, 4.11), indicating significant subgroup differences (P = 0.006). The dose-response curve indicated that the HR for OS plateaued at a cachexia prevalence range of 40%-50% (l-shaped relationship). The prevalence of cachexia in patients with cancer may vary depending on the definitive criteria used to diagnose cachexia. The HR for OS was higher for low cachexia prevalence. The definitive criteria should be carefully considered when assessing cachexia in patients with cancer. This trial was registered at the PROSPERO as CRD42023435474.
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Caquexia , Neoplasias , Caquexia/epidemiología , Caquexia/mortalidad , Caquexia/etiología , Humanos , Neoplasias/complicaciones , Neoplasias/mortalidad , Prevalencia , Femenino , Masculino , Persona de Mediana Edad , Anciano , AdultoRESUMEN
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.
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Envejecimiento Prematuro , Rayos gamma , Animales , Ratones , Masculino , Femenino , Rayos gamma/efectos adversos , Envejecimiento Prematuro/patología , Envejecimiento Prematuro/genética , Envejecimiento Prematuro/etiología , Longevidad/efectos de la radiación , Radiación Ionizante , Envejecimiento/efectos de la radiación , Caquexia/patología , Caquexia/etiología , Radioisótopos de CesioRESUMEN
Cancer cachexia is a complex systemic wasting syndrome. Nutritional mechanisms that span energy intake, nutrient metabolism, body composition, and energy balance may be impacted by, and may contribute to, the development of cachexia. To date, clinical management of cachexia remains elusive. Leaning on discoveries and novel methodologies from other fields of research may bolster new breakthroughs that improve nutritional management and clinical outcomes. Characteristics that compare and contrast cachexia and obesity may reveal opportunities for cachexia research to adopt methodology from the well-established field of obesity research. This review outlines the known nutritional mechanisms and gaps in the knowledge surrounding cancer cachexia. In parallel, we present how obesity may be a different side of the same coin and how obesity research has tackled similar research questions. We present insights into how cachexia research may utilize nutritional methodology to expand our understanding of cachexia to improve definitions and clinical care in future directions for the field.
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Composición Corporal , Caquexia , Metabolismo Energético , Neoplasias , Obesidad , Caquexia/etiología , Caquexia/terapia , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Obesidad/complicaciones , Obesidad/metabolismo , Estado Nutricional , Ingestión de EnergíaRESUMEN
BACKGROUND: Cancer cachexia is a common debilitating weight loss syndrome in advanced cancer, particularly lung cancer. Omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, with their immune-modulating effects, have been used to improve the nutritional status of patients with cancer cachexia. AIM: Evaluate the effects of omega-3 fatty acids in change in weight and lean body/skeletal mass, and health-related quality of life scores (HRQoL) in patients with advanced non-small cell lung cancer and cancer cachexia. DESIGN AND DATA SOURCES: Clinical trials from electronic databases and unpublished literature (date of last search 20 December 2023) were independently reviewed and evaluated by authors for their methodological quality. Data from eligible trials were extracted and analyzed in a meta-analysis. RESULTS: Six trials were included. Five trials (354 patients) assessed change in weight; 2 trials (132 patients) assessed change in lean body/skeletal mass and HRQoL scores (Global Health and Physical Functioning subscales). There is a significant difference in change in weight (mean difference [MD]: 1.22, 95% CI: 1.05-1.38, P < .01) and HRQoL scores (Global Health [MD: 14.40, 95% CI: 9.22-19.59, P < .01] and Physical Functioning [MD: 10.38, 95% CI: 8.50-12.27, P < .01] subscales) favoring the omega-3 fatty acids group. The change in lean body/skeletal mass is not significant (MD: 2.05, 95% CI: -0.55 to 4.66, P = .12). CONCLUSIONS: Among patients with advanced non-small cell lung cancer and cancer cachexia, supplementation with omega-3 fatty acids leads to a significant increase in weight and HRQoL scores but not in change in lean body/skeletal mass.
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Caquexia , Carcinoma de Pulmón de Células no Pequeñas , Ácidos Grasos Omega-3 , Neoplasias Pulmonares , Calidad de Vida , Humanos , Caquexia/etiología , Ácidos Grasos Omega-3/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Neoplasias Pulmonares/complicaciones , Peso Corporal/fisiología , Peso Corporal/efectos de los fármacos , Estado NutricionalRESUMEN
PURPOSE OF REVIEW: The following article examines the rationale for an inflammation-first approach for diagnosing cachexia and how the current Global Leadership Initiative on Malnutrition (GLIM) framework may be adapted to facilitate this. RECENT FINDINGS: Recently, the GLIM have published guidance on the measurement of inflammation in the context of cachexia, advocating that C-reactive protein (CRP) should be utilized for quantification. The inclusion of a systemic inflammatory biomarker for the diagnosis of cachexia questions whether it may be more aptly considered a systemic inflammatory syndrome. SUMMARY: The current consensus of the GLIM is that cachexia is 'disease-related malnutrition with inflammation'. In line with this definition, the GLIM proposed a two-step diagnostic framework: screening for malnutrition using validated screening tools and then confirming the presence of disease-related malnutrition with phenotypic (nonvolitional weight loss, low BMI, and reduced muscle mass) and aetiologic criterion reduced food intake/assimilation, and inflammation or disease burden). The GLIM are to be commended for guidance on the measurement of systemic inflammation in their current proposal, given the relative importance to clinical outcomes in patients with cancer. However, the use of CRP is somewhat rudimentary and contrasts other cancer cachexia guidelines and contemporary clinical cancer research.
Asunto(s)
Biomarcadores , Proteína C-Reactiva , Caquexia , Inflamación , Desnutrición , Neoplasias , Humanos , Caquexia/diagnóstico , Caquexia/etiología , Inflamación/diagnóstico , Desnutrición/diagnóstico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Biomarcadores/sangre , Neoplasias/complicaciones , Evaluación Nutricional , LiderazgoRESUMEN
BACKGROUND: Approximately half of all patients with hepatocellular carcinoma (HCC) develop cachexia during the course of the disease. It is important to be able to predict which patients will develop cachexia at an early stage. PURPOSE: To develop and validate a nomogram based on the magnetic resonance imaging (MRI) features of HCC and body composition for potentially predicting cachexia in patients with HCC. MATERIAL AND METHODS: A retrospective two-center study recruited the pretreatment clinical and MRI data of 411 patients with HCC undergoing abdominal MRI. The data were divided into three cohorts for development, internal validation, and external validation. Patients were followed up for six months after the MRI scan to record each patient's weight to diagnose cachexia. Logistic regression analyses were performed to identify independent variables associated with cachexia in the development cohort used to build the nomogram. RESULTS: The multivariable analysis suggested that the MRI parameters of tumor size > 5â cm (P = 0.001), intratumoral artery (P = 0.004), skeletal muscle index (P < 0.001), and subcutaneous fat area (P = 0.004) were independent predictors of cachexia in patients with HCC. The nomogram derived from these parameters in predicting cachexia reached an area under receiver operating characteristic curve of 0.819, 0.783, and 0.814 in the development, and internal and external validation cohorts, respectively. CONCLUSION: The proposed multivariable nomogram suggested good performance in predicting the risk of cachexia in HCC patients.
Asunto(s)
Composición Corporal , Caquexia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Nomogramas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/complicaciones , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Caquexia/diagnóstico por imagen , Caquexia/etiología , Estudios Retrospectivos , Anciano , Valor Predictivo de las Pruebas , AdultoRESUMEN
Cancer cachexia, the unintentional loss of lean mass, contributes to functional dependency, poor treatment outcomes, and decreased survival. Although its pathogenicity is multifactorial, metabolic dysfunction remains a hallmark of cachexia. However, significant knowledge gaps exist in understanding the role of skeletal muscle lipid metabolism and dynamics in this condition. We examined skeletal muscle metabolic dysfunction, intramyocellular lipid droplet (LD) content, LD morphology and subcellular distribution, and LD-mitochondrial interactions using the Lewis lung carcinoma (LLC) murine model of cachexia. C57/BL6 male mice (n = 20) were implanted with LLC cells (106) in the right flank or underwent PBS sham injections. Skeletal muscle was excised for transmission electron microscopy (TEM; soleus), oil red O/lipid staining [tibialis anterior (TA)], and protein (gastrocnemius). LLC mice had a greater number (232%; P = 0.006) and size (130%; P = 0.023) of intramyocellular LDs further supported by increased oil-red O positive (87%; P = 0.0109) and "very high" oil-red O positive (178%; P = 0.0002) fibers compared with controls and this was inversely correlated with fiber size (R2 = 0.5294; P < 0.0001). Morphological analyses of LDs show increased elongation and complexity [aspect ratio: intermyofibrillar (IMF) = 9%, P = 0.046) with decreases in circularity [circularity: subsarcolemmal (SS) = 6%, P = 0.042] or roundness (roundness: whole = 10%, P = 0.033; IMF = 8%, P = 0.038) as well as decreased LD-mitochondria touch (-15%; P = 0.006), contact length (-38%; P = 0.036), and relative contact (86%; P = 0.004). Furthermore, dysregulation in lipid metabolism (adiponectin, CPT1b) and LD-associated proteins, perilipin-2 and perilipin-5, in cachectic muscle (P < 0.05) were observed. Collectively, we provide evidence that skeletal muscle myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in a preclinical model of cancer cachexia.NEW & NOTEWORTHY We sought to advance our understanding of skeletal muscle lipid metabolism and dynamics in cancer cachexia. Cachexia increased the number and size of intramyocellular lipid droplets (LDs). Furthermore, decreases in LD-mitochondrial touch, contact length, and relative contact along with increased LD shape complexity with decreases in circularity and roundness. Dysregulation in lipid metabolism and LD-associated proteins was also documented. Collectively, we show that myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in cancer cachexia.