Cancer cachexia is characterized by involuntary weight loss and wasting of fat and muscle, with diminished food intake commonly cited as a cause. However, the extent to which reduced food intake drives these symptoms, and other phenotypes such as physical weakness, remains unclear. Using the colon carcinoma 26 (C26) mouse model, we assessed the role of food intake in key cachexia phenotypes. We found that reduced food intake was the predominant driver of body weight loss and tissue wasting, suggesting no additional causal mechanisms. In contrast, food intake reduction did not affect physical performance, indicating food intake-independent factors in causing weakness. Thus, depending on the model or patient group, reduced food intake may primarily drive some cachectic phenotypes while having no role in others. Discriminating between food intake-mediated effects and those independent of it is critical for guiding research focus and unraveling the causal pathways of cancer cachexia.

Purpose: Cachexia, characterized by involuntary weight loss, muscle wasting, and metabolic dysfunction, is prevalent in advanced cancer and chronic illnesses. Despite its impact, outpatient treatment models in the U.S. remain limited and unstandardized. Here, we aim to describe the structure, implementation, patient characteristics, and real-world clinical trajectories of a multidisciplinary clinic for cancer cache as well as other forms of unintentional weight loss clinic within an academic endocrinology practice. Methods: We conducted a retrospective observational cohort study of 103 patients referred to a single-center unintentional weight loss clinic over five years. Patients received comprehensive assessments (weight trajectory, nutrition status, 5× sit-to-stand test, handgrip strength) and personalized interventions including nutrition counseling, resistance training, and pharmacologic therapies. Results: Among 103 patients (median age 69.7 years; 53% male), 64% had cancer, while 36% were referred for non-malignant causes of weight loss or cachexia. Reduced appetite or food intake was reported in 43%, and functional impairment was common, with low handgrip strength in 47% and impaired 5× sit-to-stand performance in 79% of assessed patients. Systemic abnormalities were frequent, including elevated hs-CRP (57%), elevated neutrophil-to-lymphocyte ratio (43%), and hypoalbuminemia (26%). Among patients with available paired follow-up data, the median rate of weight change shifted from -0.5 kg/month prior to enrollment to 0.0 kg/month three months after the initial visit (p < 0.0001). Five-times sit-to-stand performance improved modestly at three months (p = 0.042), while handgrip strength was unchanged. Half of patients that engaged with the clinic returned for at least follow-up, but there was no identifiable difference between the population of patients that returned versus those that did not. Conclusions: A structured, multidisciplinary unintentional weight loss clinic in an endocrinology setting was associated with stabilization of weight and modest changes in physical function in this single-center cohort among patients who engaged in follow-up. These findings highlight the successful implementation of integrated outpatient care models and provide practice-based context for future interventions and therapeutic evaluations.

Tuberculous pericarditis is a rare but important cause of constrictive pericarditis in developed countries, while remaining a significant public health concern in endemic regions. Myocardial involvement is uncommon and often underrecognized. A previously healthy 47-year-old man presented with a five-year history of progressive bilateral lower-limb edema and exertional dyspnea, with marked deterioration over the last five months, including severe fatigue and involuntary weight loss of 8 kg. On admission, imaging revealed biventricular systolic dysfunction, pericardial thickening with calcifications, and bilateral pleural effusions. Pleural fluid analysis demonstrated an exudative effusion with markedly elevated adenosine deaminase (ADA) levels (130 U/L), consistent with tuberculous pleuritis. Cardiac magnetic resonance imaging confirmed myopericarditis with diffuse pericardial thickening (up to 6 mm) and late gadolinium enhancement. Right heart catheterization demonstrated findings consistent with constrictive physiology. Given the presence of severe ventricular dysfunction, atrial fibrillation, and active extrapulmonary tuberculosis, pericardiectomy was deferred. Antituberculous therapy and guideline-directed medical treatment for heart failure were initiated. At three-month follow-up, the patient demonstrated mild functional improvement and continued on a standard six-month antituberculous regimen, which was ongoing at the time of reporting. In endemic areas, tuberculosis should be considered an important cause of constrictive pericarditis in patients with unexplained pericardial disease. Multimodality imaging is essential for accurate diagnosis and for guiding management, especially in complex presentations involving both the pericardium and myocardium. This case illustrates the diagnostic value of a multimodality approach and the management strategy in a high-risk surgical candidate.

Cancer cachexia (CC) is characterized by organ wasting and ensuing involuntary weight loss. Despite advances, underlying mechanisms initiating CC remain unclear, including early symptoms like anorexia. Here, we use a fly gut-tumor model with a precise time-window before organ wasting starts. We show that tumor-induced factors involved in inflammation (unpaired 3/ Interleukin-6-like) and reduced insulin signaling (ImpL2/ Insulin Growth Factor Binding Protein) decrease NPF (Neuropeptide F/ Neuropeptide Y) in the brain prior to organ wasting. This early NPF decrease triggers low protein-specific food appetite and anorexia. We find that ImpL2 reduces NPF signaling while upd3 helps by concurrently affecting the blood brain barrier. Tumor-induced NPF decrease, and early reduction of protein appetite drive the onset of weight loss and exacerbate the risk of death during organ wasting. Altogether, we provide evidence for an early orexigenic brain imbalance causing low protein appetite that regulates the onset and outcome of organ wasting.

Cancer cachexia is a multifactorial syndrome marked by involuntary weight loss, skeletal muscle wasting, adipose tissue remodeling, and systemic metabolic dysfunction. Exosome-derived microRNAs (miRNAs) have emerged as key mediators, reprogramming host tissues and driving these hallmarks. However, no integrated framework has linked exosomal miRNAs to the proteomic and metabolomic alterations that characterize cachexia. This review critically synthesizes evidence on exosomal miRNAs in muscle atrophy, adipose browning, and systemic metabolic disruption. Tumor-secreted exosomal miRNAs activate proteolytic pathways (miR-21/29a via TLR7/8NF-κB/JNK), suppress antiapoptotic signals (miR-195a/125b targeting BCL-2), induce ER stress (miR-181a-3p), impair mitochondrial quality control (miR-122), and remodel metabolic signaling (miR-155, miR-183-5p). These mechanisms converge to produce proteomic signatures of enhanced proteolysis, apoptosis, and lipolysis, alongside metabolomic shifts toward amino acid efflux, fatty acid mobilization, and glycolytic inefficiency. This is the first integrated review linking exosomal miRNAs with proteomic and metabolomic signatures of cancer cachexia, offering a multiomics framework for biomarker discovery and therapeutic targeting. We highlight their potential as early biomarkers, therapeutic targets, and modulators of rehabilitation response, while outlining research gaps including limited clinical validation, intertumor heterogeneity, and the need for multiomics integration to advance translation into patient care.

Metoclopramide is excreted in variable amounts in breastmilk. After oral and intranasal administration, most infants would receive less than 10% of the maternal weight-adjusted dosage, but some receive doses that achieve pharmacologically active serum levels, elevated serum prolactin and possible gastrointestinal side effects. Although most studies have found no adverse effects in breastfed infants during maternal metoclopramide use, many did not adequately observe for side effects. Metoclopramide is used as a galactogogue.[1] Metoclopramide increases serum prolactin. A meta-analysis of 5 placebo-controlled studies concluded that 2 weeks of metoclopramide caused no increase of serum prolactin over placebo, but 3 weeks of treatment did.[2] A more recent meta-analysis concluded that metoclopramide was of no benefit as a galactogogue in the mothers of preterm infants.[3] The clinical value of metoclopramide in increasing milk supply is questionable. Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production.[4,5] In well-designed studies that evaluated the effectiveness of metoclopramide as a galactogogue in women who continue to have difficulty producing milk after nursing techniques have been optimized, it was of no additional benefit. Prophylactic use in the mothers of preterm infants has also shown little or no benefit. Metoclopramide has no officially established dosage for increasing milk supply. Most studies have used metoclopramide in a dosage of 10 mg 2 or 3 times daily for 7 to 14 days. Some studies used a tapering dosage for the last days few of the regimen to avoid an abrupt drop in milk supply after drug discontinuation. No published literature supports the efficacy or safety of higher dosages, longer treatment periods or repeated courses of therapy. Postpartum mothers are at a relatively high risk for postpartum depression and metoclopramide can cause depression as a side effect. Therefore, metoclopramide should probably be avoided in women with a history of major depression and not used for prolonged periods in any mothers during this time of high susceptibility.[6,7] Long-term uses of metoclopramide also increases the risk of tardive dyskinesia.[8] Other reported side effects in nursing mothers include tiredness, nausea, headache, diarrhea, dry mouth, breast discomfort, vertigo, restless legs, intestinal gas, hair loss, irritability and anxiety.[7,9-11] In a survey of nursing mothers in the United States, 32 had used metoclopramide as a galactogogue and all reported having experienced an adverse reaction from the drug.[12] A larger survey of women taking metoclopramide for lactation enhancement found that 4.8% of women had either palpitations or racing heart rate, 12% reported depression, and 1 to 7% reported other central nervous system side effects ranging from dizziness and headache to involuntary grimacing and tremors. Diarrhea, irritability and fatigue were also relatively common.[13]

Chorea is a hyperkinetic movement disorder characterized by involuntary, spontaneous, irregular, purposeless movements that flow unpredictably from one body part to another. An overlap between movement disorders and neuroendocrine abnormalities is widely recognized; however, chorea is a rare complication of hyperthyroidism. In this case report, we present a case of unilateral upper limb chorea as a manifestation of hyperthyroidism. We describe a clinical case of a 21-year-old male who presented repeatedly to the emergency department (ED) with acute-onset, involuntary proximal movements of the left upper limb (LUL), arrhythmic in nature, without involvement of the face, trunk, or lower limbs (LLs). Neurological examination and investigations (cerebral magnetic resonance imaging, electroencephalogram, cerebral computed tomography angiography, and lumbar puncture) were unremarkable, except for the involuntary purposeless movements previously mentioned. During a subsequent admission for recurrent symptoms, the patient was diagnosed with acute appendicitis. Concurrent laboratory evaluation revealed thyrotoxicosis with suppressed TSH, elevated free T4 and T3, and positive TSH-receptor antibodies, confirming Graves' disease. Surgical intervention was postponed due to the risk of thyroid storm, and the patient was admitted to the intensive care unit for stabilization and initiation of antithyroid therapy. Treatment with methimazole, propranolol, cholestyramine, hydrocortisone, and Lugol's iodine led to normalization of thyroid function and complete resolution of hemichorea on follow-up, supporting a causal link to thyrotoxicosis. Hemichorea is rare in patients with hyperthyroidism, but it can be the first manifestation of the condition. This clinical case draws attention to an atypical presentation of Graves' disease and its challenges. This initial presentation may experience a delayed diagnosis, as hyperthyroidism is not typically the first consideration, and usually presents with other symptoms, such as palpitations, weight loss, heat intolerance, irritability, proptosis, and hyperhidrosis. Early recognition and proper diagnosis are essential, as treating the underlying disease may lead to rapid resolution of chorea and avoid unnecessary treatments.

Malnutrition is highly prevalent among oncology patients, with large-scale studies reporting involuntary weight loss in 31-87%, depending on tumour site and disease stage. A combination of nutrition-impact symptoms, reduced oral intake and systemic inflammation lead to poor tolerance to treatment, diminished quality of life and reduced survival. Systemic inflammation is a hallmark of cancer-associated malnutrition and contributes to loss of lean mass and abnormal body composition phenotypes (sarcopenia, cachexia and low muscle density) which may coexist with overweight and obesity. Malnutrition screening tools are widely used to identify patients at risk; however, traditional weight and BMI-based instruments such as the Malnutrition Screening Tool (MST) and Malnutrition Universal Screening Tool (MUST) frequently misclassify patients with cancer as well-nourished. These tools fail to account for nutrition-impact symptoms, inflammation and muscle wasting. Although obesity is an established cancer risk factor, 40-60% of patients with metastatic disease remain overweight or obese during treatment. When screening tools are BMI-based, high fat stores mask muscle wasting, leading to misclassification of nutritional risk and delayed dietetic referrals. To improve detection, screening tools should incorporate patient-reported symptoms, inflammatory markers and body composition assessment, enabling earlier, proactive nutritional care. Alternatively, it may be time to acknowledge that all cancer patients are inherently 'at-risk' of malnutrition and to prioritise universal access to dietetic support from diagnosis through treatment. This review summarises current malnutrition screening and assessment practices in oncology and outlines key considerations for future research and clinical practice.

Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, predominantly caused by muscle wasting. While tumors can elicit detrimental effects on skeletal muscle function, the contribution of specific tumor-derived mediators remains elusive. To explore this, we investigated the impact of conditioned media (CM) from four cachexia-inducing tumor cell lines (KPC, 4662, LLC, and C26) on muscle differentiation using C2C12 cells. Creatine kinase (CK) activity was measured as an indicator of muscle wasting, and global gene expression changes in C2C12 cells were analyzed via RNA sequencing. Cytokine profiling of the CM identified 111 immune factors, and mimic combinations of the most abundant cytokines from KPC CM were tested for their effects on CK activity. Additionally, the involvement of tumor-derived PGE2 was assessed via CRISPR/Cas9-mediated knockout of the Ptgs2 gene in KPC cells. CM from all tumor cell lines significantly reduced CK activity in C2C12 cells, consistent with downregulation of CKm gene expression. Global gene expression profiles revealed upregulation of immune-related pathways in C2C12 cells exposed to KPC CM. However, mixtures of the 14 most abundant cytokines in CM had minimal effects on CK activity, and tumor-derived PGE2 showed no significant effect on CK activity or muscle cell differentiation. These findings suggest that the observed muscle-wasting effects of cachexia-inducing tumor cells cannot be replicated by the most abundant cytokines present in CM alone, highlighting the need for further research to identify the key tumor-derived factors responsible for cancer-induced muscle wasting.