Cachexia

Cachexia is hard to define because it often happens alongside malnutrition and sarcopenia. Since there are no clear rules separating these conditions, experts continue working to agree on definitions to help treat these nutrition-related problems. In the past, cachexia was described as "a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass." They also suggested breaking it into three stages: pre-cachexia, cachexia, and refractory cachexia. The difference is sarcopenia is caused by aging, while cachexia happens due to long-term disease and inflammation. ==Causes==

Cachexia is most commonly associated with end-stage cancer, often called cancer cachexia. Other conditions that frequently cause cachexia include: • Congestive heart failure • AIDS • Chronic obstructive pulmonary disease • Chronic kidney disease Cachexia can happen in late stages of diseases like cystic fibrosis, multiple sclerosis, motor neuron disease, Parkinson's disease, dementia, tuberculosis, multiple system atrophy, mercury poisoning, Crohn's disease, trypanosomiasis, rheumatoid arthritis, celiac disease, and other diseases that affect the entire body. ==Mechanism==

The way cachexia works is not well understood, but research suggests the cause is linked to these main processes in the body: inflammation, changes in metabolism, and hormone changes in the body. It also triggers the release of other cytokines that also speed up muscle loss. Since this process is very complex, cachexia is unlikely to be caused by one molecule. IL-6 is produced by immune cells called macrophages, potentially producing acute phase reactants which may worsen muscle loss. • Activin - May contribute to muscle loss when TNF is also active. In addition, uncontrolled inflammation in people with cachexia increases the body's need for nutrients. Furthermore, people with long-term illness such as cancer are frequently treated with glucocorticoids, making cachexia more likely in these individuals. Some tumors produce a molecule called parathyroid-related peptide (PTHrP). It increases metabolism by stimulating energy production in the mitochondria of fat cells. Leptin is a hormone known to decrease appetite. People with cachexia often have high leptin levels, making them feel less hungry. The hypothalamus, the brain's appetite control center, is also affected in cachexia. Given the hypothalamic function in controlling appetite, it is believed to play a role in cachexia. The appetite-controlling center of the hypothalamus is controlled by neuropeptide Y (NPY) and agouti gene-related protein (AgRP) that increase appetite, as well as proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcrip (CART) that decrease appetite. Inflammation may disrupt these appetite signals, causing reduced hunger and leading to further weight and muscle loss. However, scientists are still studying exactly how this process works. ==Diagnosis==

Doctors formerly diagnosed cachexia mainly by looking at changes in body weight. A person was considered to have cachexia if they had a low BMI or unwanted weight loss of more than 10%. These weight-based criteria do not account for muscle loss, which is a key part in cachexia. . However, it has no widely accepted definition. • For people with a BMI of less than 20 kg/m2, weight loss of more than 2%. • Refractory cachexia (9–12 points) – Severe weight and muscle loss with poor response to treatment and a life expectancy of less than 3 months. The Cachexia SCOre (CASCO) is another scoring system that looks at weight loss, inflammation, metabolism, immune function, physical ability, appetite, and quality of life to provide a more detailed assessment. Laboratory tests Laboratory tests are sometimes used to check for cachexia. Tests that are used include albumin, C-reactive protein, ghrelin, IGF-2, and leptin. Acute phase reactants (IL-6, IL-1b, tumor necrosis factor, IL-8, interferon gamma and serum cytokines are also studied but are not always reliable for predicting cachexia. Laboratory cut-off values are also not the same across different institutions. There is no single lab test that can confirm cachexia or predict whether it will develop. Imaging One challenge in diagnosing cachexia is measuring muscle loss in an easy and affordable way. Some imaging techniques that can help assess body composition include: • Bioelectrical impedance analysis (BIA) • Computed tomography (CT scans) • Dual-energy X-ray absorptiometry (DEXA) • Magnetic resonance imaging (MRI) However, these methods are not widely used because they can be expensive and difficult to access. ==Treatment==

Because cachexia is a complex condition with several potential causes, treatment requires multiple approaches at the same time. For example, people with cachexia caused by AIDS often improve after starting treatment for AIDS. However, because the exact mechanism of cachexia is unclear, there is no single medication that can effectively treat it. Many people with cachexia also avoid exercise because they lack motivation or fear that it will worsen their symptoms. Nutrition Cachexia can increase metabolism and suppress appetite, worsening the present muscle loss. Recommendations include 1.5g/kg/day of protein, making up 15-20% of daily calories. Medications Some medications, such as glucocorticoids, cannabinoids, and progestins were initially used in treating cachexia and aim to increase appetite. However, other TNF inhibitors have not shown the same promising results. Supplements The use of certain amino acids may slow muscle breakdown by providing the body with the building blocks needed for metabolism of muscle and glucose. Specifically, leucine and valine may block muscle breakdown. Glutamine is used in oral supplements for people with advanced cancer or HIV/AIDS. β-hydroxy β-methylbutyrate (HMB) is a molecule that comes from leucine that promotes muscle growth. Studies show positive results for chronic pulmonary disease, hip fracture, and in AIDS-related and cancer-related cachexia. However, it is often studied along with other nutrients, making it difficult to assess its effects alone. Creatine supplementation may help reduce muscle wasting, though more research is needed. ==Epidemiology==

Accurate epidemiological data on the prevalence of cachexia is lacking due to changing diagnostic criteria and under-identification of people with the disorder. It is estimated that cachexia from any disease is estimated to affect more than 5 million people in the United States. Recent updates show that 33%-51.8% of people with cancer develop cachexia, though estimates vary widely and may be unreliable due to absence of consensus guidelines for diagnosis, variability in cancer populations, and variability in timing of diagnosis. Specifically, the highest rates were seen in older populations as well as those with upper gastrointestinal, colorectal, and lung cancers, respectively. Cachexia is considered the immediate cause of death of many people with cancer, estimated between 22 and 40%. ==History==

The word "cachexia" is derived from the Greek words "Kakos" (bad) and "hexis" (condition). English ophthalmologist John Zachariah Laurence was the first to use the phrase "cancerous cachexia", doing so in 1858. He applied the phrase to the chronic wasting associated with malignancy. It was not until 2011 that the term "cancer-associated cachexia" was given a formal definition, with a publication by Kenneth Fearon. Fearon defined it as "a multifactorial syndrome characterized by ongoing loss of skeletal muscle (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment". ==Research==

Several medications are under investigation or have been previously trialed for use in cachexia but are not in widespread clinical use: • Thalidomide • Non-steroidal anti-inflammatory drugs • Hydrazine sulfate Hawaii and Connecticut. Multimodal therapy Despite the extensive investigation into single therapeutic targets for cachexia, the most effective treatments use multi-targeted therapies. In Europe, a combination of non-drug approaches including physical training, nutritional counseling, and psychotherapeutic intervention are used in belief this approach may be more effective than monotherapy. Administration of anti-inflammatory drugs showed efficacy and safety in the treatment of people with advanced cancer cachexia. == See also ==