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

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.
CONCLUSIONS: We developed two models for identifying precachexia and cachexia, which will help clinicians detect and diagnose precachexia.

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.
CONCLUSIONS: Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.

(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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.
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.

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.
CONCLUSIONS: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.

GDF15 (growth differentiation factor 15), also known as macrophage inhibitory cytokine 1 (MIC-1), is a circulating protein involved in the regulation of energy balance and weight control. Elevated levels of GDF15 have been associated with cachexia and reduced survival rates in cancer patients. Through the activation of the GFRAL (GDNF-family receptor α-like)-RET (Rearranged during Transfection) signaling pathway, GDF15 can induce weight loss, making it a potential target for treating cachexia. Currently, there are no approved antibody drugs specifically targeting GDF15 for cancer cachexia treatment. However, efforts have been made to develop antibody-based therapeutics against this emerging target. In this study, we generated a monoclonal antibody KY-NAb-GDF15 against GDF15 that effectively blocks downstream signaling mediated by GFRAL upon stimulation by GDF15. This antibody demonstrates robust neutralizing activity and exhibits high binding specificity. Importantly, our findings indicate that this antibody holds promise in alleviating cancer-induced cachexia and mitigating chemotherapy-induced weight loss, thereby offering significant therapeutic potential for managing cancer cachexia.

BACKGROUND: High doses of glucocorticoids and severe weight loss can cause osteoporosis. We present a case of glucocorticoid-induced osteoporosis and cachexia in an 18-year-old woman who experienced severe appetite loss leading to weight loss, amenorrhea, and multiple thoracolumbar compression fractures.
METHODS: The patient had been receiving high-dose glucocorticoid treatment for systemic lupus erythematosus since the age of 13 and developed unexplained appetite loss since the age of 16. She subsequently developed thoracolumbar compression fractures, which necessitated repeated hospitalization. Gradual glucocorticoid tapering using belimumab and weight regain were achieved through high-calorie nutrition administration via the central vein, which helped the patient overcome her cachexic state. Romosozumab administration increased bone mineral density.
CONCLUSIONS: Long-term administration of glucocorticoids may lead to osteoporosis and cachexia, resulting in amenorrhea, especially in young adults. Approaches that taper glucocorticoids and promote weight regain may be helpful in the management of such patients.

UNASSIGNED: Skeletal muscle wasting (SMW) is highly prevalent in patients with heart failure (HF) at left ventricular assist device (LVAD) implantation and is associated with morbidity and mortality. At the same time, SMW is clinically under-recognized, while exercise training (ET) studies in weak LVAD patients are lacking.
UNASSIGNED: A 60-year-old man with advanced HF, SMW, cardiac cachexia, and frailty was confined in bed for 6 months initially supported with intravenous inotropes and subsequently with an intra-aortic balloon pump. His frailty was recognized as an LVAD-responsive frailty, and patient was successfully implanted with a HeartWare (Medtronic). Post-surgery, patient was very weak, unable even to move in bed without assistance. We evaluated skeletal muscle using simple tools such as the Oxford scale, mid-thigh circumference, hand-held dynamometry, and maximum inspiratory pressure. Physical performance was assessed with the sit to stand test, gait speed test, pedal bike timing, and the 6 min walk test. On top of routine physiotherapy, patient underwent an 8-week modified aerobic/resistance/inspiratory (ARIS) ET programme at moderate intensity and showed significant improvements in skeletal muscle mass and strength and physical and functional capacity.
UNASSIGNED: We want to emphasize the importance of skeletal muscle evaluation at LVAD implantation and the feasibility and effectiveness of early ARIS training in very weak patients.