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Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management.

Background The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. Methods Body composition from 500 women in the Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). Results Overweight or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50). Conclusions Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors. [ABSTRACT FROM AUTHOR]

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

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‐1β (IL‐1β) expression and release from extensor digitorum longus muscle fibres. Moreover, IL‐1β 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‐1β 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‐1β 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‐1β‐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‐1β‐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‐1β to mitigate cancer cachexia‐induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Purpose: of review To explore the contributions of recent qualitative literature in progressing understanding of the experiences of cancer cachexia, and its management, from the perspectives of patients and unpaid/family carers. Recent findings: Challenges with conducting everyday activities, maintaining independence, and continuing usual roles within the family are sources of distress. Patients and carers value individualization, flexibility, and carer involvement in physical activity/exercise interventions. In psychosocial/educational interventions that were positively perceived, the opportunity to talk about cachexia was appreciated, leading to improved health literacy, awareness about nutrition, and relationships with food. However, the general patient and carer experience around clinical acknowledgement and management of cachexia remains poor. Summary: Eating-related distress and conflicts, lack of understanding about cachexia, and the visibility of weight loss remain recurring themes amongst literature on experiences of cancer cachexia. Studies exploring preferences for, and experiences of, interventions have primarily focused on physical activity or exercise. Psychosocial/educational and physical activity/exercise interventions are valued and perceived to alleviate some of the key quality of life issues amongst patients with cancer cachexia and their unpaid/family carers. [ABSTRACT FROM AUTHOR]

Purpose: of review Comprehensive supportive care interventions for patients with lung cancer are being investigated in a range of ways, including: early palliative care, prehabilitation and rehabilitation. We review recent literature on supportive care and propose a traffic light system to individualise comprehensive supportive care. Green for those very likely to receive anti-cancer treatment, red for those very unlikely to receive anti-cancer treatment and orange where the chance of accessing treatment is uncertain. Comprehensive supportive care can be individualised based on the group a particular patient is in. Recent findings: Lung cancer outcomes are improving with the availability of increasingly efficacious treatments; however, treatment rates for advanced disease remain low. In this review, we discuss how person-centred outcomes could be improved, how outcomes can be prognosticated and how the 'host' can be staged as well as the cancer. Recent data suggests that early comprehensive supportive care improves quality of life, reduces time spent in hospital and may affect survival. Summary: Comprehensive supportive care is likely to improve quality of life in patients with advanced lung cancer. Further work is needed to see if it can improve treatment rates and survival. [ABSTRACT FROM AUTHOR]

Purpose: of review Cachexia is a devasting syndrome which impacts a large number of patients with cancer. This review aims to provide a comprehensive overview of the central mechanisms of cancer cachexia. In particular, it focuses on the role of the central nervous system (CNS), the melanocortin system, circulating hormones and molecules which are produced by and act on the CNS and the psychological symptoms of cancer cachexia. Recent findings: A growing body of evidence suggests that a central mechanism of action underpins this multi-system disorder. Recent research has focused on the role of neuroinflammation that drives the sickness behaviour seen in cancer cachexia, with emphasis on the role of the hypothalamus. Melanocortin receptor antagonists are showing promise in preclinical studies. There are also new pharmacological developments to overcome the short halflife of ghrelin. GDF-15 has been identified as a core target and trials of compounds that interfere with its signalling or its central receptor are underway. Summary: Understanding the central mechanisms of cancer cachexia is pivotal for enhancing treatment outcomes in patients. While emerging pharmacological interventions targeting these pathways have shown promise, further research is essential. [ABSTRACT FROM AUTHOR]

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

Rationale: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Our previous studies have identified that nocturnal hypoxemia causes skeletal muscle loss (i.e., sarcopenia) in in vitro models of COPD. Objectives: We aimed to extend our preclinical mechanistic findings by analyzing a large sleep registry to determine whether nocturnal hypoxemia is associated with sarcopenia in patients with COPD. Methods: Sleep studies from patients with COPD (n = 479) and control subjects without COPD (n = 275) were analyzed. Patients with obstructive sleep apnea, as defined by apnea–hypopnea index ⩾ 5, were excluded. Pectoralis muscle cross-sectional area (PMcsa) was quantified using computed tomography scans performed within 1 year of the sleep study. We defined sarcopenia as less than the lowest 20% residuals for PMcsa of control subjects, which was adjusted for age and body mass index (BMI) and stratified by sex. Youden's optimal cut-point criteria were used to predict sarcopenia based on mean oxygen saturation during sleep. Additional measures of nocturnal hypoxemia were analyzed. The pectoralis muscle index (PMI) was defined as PMcsa normalized to BMI. Results: On average, males with COPD had a 16.6% lower PMI than control males (1.41 ± 0.44 vs. 1.69 ± 0.56 cm2/BMI; P < 0.001), whereas females with COPD had a 9.4% lower PMI than control females (0.96 ± 0.27 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). Males with COPD with nocturnal hypoxemia had a 9.5% decrease in PMI versus COPD with normal O2 (1.33 ± 0.39 vs. 1.47 ± 0.46 cm2/BMI; P < 0.05) and a 23.6% decrease compared with control subjects (1.33 ± 0.39 vs. 1.74 ± 0.56 cm2/BMI; P < 0.001). Females with COPD with nocturnal hypoxemia had an 11.2% decrease versus COPD with normal O2 (0.87 ± 0.26 vs. 0.98 ± 0.28 cm2/BMI; P < 0.05) and a 17.9% decrease compared with control subjects (0.87 ± 0.26 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). These findings were largely replicated using multiple measures of nocturnal hypoxemia. Conclusions: We defined sarcopenia in the pectoralis muscle using residuals that take into account age, BMI, and sex. We found that patients with COPD have a lower PMI than patients without COPD and that nocturnal hypoxemia was associated with an additional decrease in the PMI of patients with COPD. Additional prospective analyses are needed to determine a protective threshold of oxygen saturation to prevent or reverse sarcopenia due to nocturnal hypoxemia in COPD. [ABSTRACT FROM AUTHOR]

Background: Malnutrition, defined as weight loss and unsatisfactory nutrient intake, is very common in patients with head and neck squamous cell carcinoma (HNSCC) in either the early or palliative setting. Despite increased awareness, nutritional programs are not yet adequately implemented in these patients. There are several reasons for this delay: differences in composition, the expertise of the multidisciplinary teams involved in HNSCC patients' treatment, and economic and network resources conditioning faster or slower nutritional supply delivery. This situation affects the outcomes and the quality of life of HNSCC patients. Materials and methods: We investigated available literature about nutritional support in HNSCC patients and its impact on outcomes, prognosis, and quality of life, and we focused on the role of the multidisciplinary team. We considered 8,491 articles, and after excluding duplicates and manuscripts not written in English, 1,055 were analyzed and 73 were deemed eligible for the present work. Results: After the literature review, we can state that malnutrition, sarcopenia, and cachexia are associated with systemic inflammation and closely correlated with poor outcomes. An evaluation of the nutritional status of the multidisciplinary team before, during, and after therapy could improve patient outcomes, as the goal of the therapeutic approach is widely designed. Conclusions: We suggest that the treatment workflow definition is fundamental and propose a tailored nutritional approach that could benefit HNSCC patients' outcomes and quality of life. These results could be achieved by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AbstractCancer cachexia, characterized by the progressive loss of skeletal muscle mass, leads to functional impairment and poor prognosis. Anamorelin is approved for treating cancer cachexia in Japan; however, the factors influencing its discontinuation and the impact of combining anamorelin with rehabilitation remain unclear. Therefore, we retrospectively analyzed 82 patients with cancer cachexia to identify factors associated with anamorelin discontinuation and assess changes in nutritional status and motor function using non-dominant handgrip strength after 12 wk. Patients received outpatient rehabilitation, combining resistance and aerobic training every two weeks, alongside anamorelin therapy. Our findings indicate that patients with an ECOG performance status of 1 or 2 were less likely to continue anamorelin therapy for 12 wk compared to those with a performance status of 0 (odds ratio 2.71; 95% CI 1.05 − 7.00; p = 0.040). Significant improvements were observed in body weight (48.8 to 53.7 kg, p < 0.001), skeletal muscle mass (6.4 to 6.9 kg/m2, p < 0.001), FAACT score (11.5 to 18.0, p < 0.001), and non-dominant handgrip strength (20.5 to 21.7 kg, p = 0.018) after 12 wk. Early initiation of anamorelin with regular rehabilitation is recommended to enhance nutritional status and motor function in patients with cancer cachexia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The experience of bearing witness to the lack of appetite and involuntary weight loss that characterizes cancer anorexia–cachexia syndrome (CACS) is reported to be stressful for family members. Research identifies that family members engage in a wide range of behaviors in response to a relative who shows minimal interest in eating and is literally 'wasting away' before their eyes. Some families, though concerned about the symptoms of CACS, do not dwell excessively on the patient's nutritional intake while others continually harass the patient to eat and petition health care providers for aggressive nutritional interventions to eat in an attempt to stave off further physical deterioration. While studies have detailed how family members respond to a terminally ill relative with CACS, empirical work explicating the explanatory models of CACS that they hold is lacking. Explanatory models (EMs) reflect the beliefs and ideas that families have about why illness and symptoms occur, the extent to which they can be controlled, how they should be treated, and how interventions should be evaluated. To address this gap in the literature, a grounded theory study guided by Kleinman's Explanatory Model questions was conducted with 25 family members of advanced cancer patients. The core category of 'Wayfaring' integrates the key categories of the model and maps onto Kleinman's questions about CACS onset, etiology, natural course, physiological processes/anatomical structures involved, treatment, and the impacts of disease on patient and family. Findings suggest that a divergence between some biomedical constructions of CACS and explanatory models held by family members may fuel the family–health care provider conflict, thereby providing direction for communication with families about care of the patient with anorexia–cachexia. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

Female hormones, functioning as neuroactive steroids, are utilized beyond menopausal hormone therapy. The rapid onset of allopregnanolone analogs, such as brexanolone and zuranolone, in treating depression, and the effectiveness of megestrol acetate in addressing appetite and weight gain, prompted the Food and Drug Administration to authorize the use of progesterone for treating postpartum depression and cancer-related cachexia. Progesterone has also been found to alleviate neuropathic pain in animal studies. These off-label applications offer a promising option for patients with advanced cancer who often experience various mood disorders such as depression, persistent pain, social isolation, and physical complications like cachexia. These patients have shown low tolerance to opioids and mood-regulating medications. However, the potential risks and uncertainties associated with hormone therapy treatment modalities can be daunting for both patients and medical professionals. This review aims to offer a comprehensive understanding of the non-reproductive functions and mechanisms of female hormones in brain health. [ABSTRACT FROM AUTHOR]