Pre-conception and pregnancy management of bipolar disorder.

Cancer-associated cachexia (CAC) is a complex, multifactorial metabolic syndrome. The primary clinical criteria for CAC include weight loss exceeding 5% in 6 months or more than 2% in individuals with a body mass index (BMI) below 20 kg/m, accompanied by at least three secondary criteria: muscle mass depletion, asthenia (physical weakness), body fat loss, anorexia, or abnormal biochemical markers . The prevalence of CAC manifestations in cancer patients is as high as 85% in some cancers, with pancreatic and lung cancers being among the highest. About 30% of all cancer deaths are directly attributed to CAC . CAC plays a crucial role in cancer progression and outcome as it increases chemotherapy toxicity, resistance to therapy, and complications from surgeries, decreases in quality of life, and higher mortality rates . While CAC is most prominent in end-stage cancers, for some tumor types CAC is present before the tumor is clinically detectable . Unfortunately, there are no effective clinical treatments for CAC; no correlation has been demonstrated between dietary intake and body composition parameters and pharmacologic interventions have failed to produce significant improvements in clinical settings . The challenge associated with treating CAC is due to its nature as a complex systemic syndrome involving tumor-derived catabolic factors and pro-inflammatory molecules derived from tumor-immune crosstalk that promote systemic changes, e.g., eating behavior, glycolysis, proteolysis, and lipolysis . These metabolic alterations contribute to excess energy consumption beyond that attributable to the tumor, which likely stimulates the breakdown of fat and muscle tissues . Notably, the liver primarily regulates key metabolic pathways altered in CAC. In cachectic patients, the liver manifests aberrant function in metabolic pathways such as gluconeogenesis, lipid metabolism, albumin synthesis, and the urea cycle, contributing to the metabolic symptoms present in cachexia . CAC results from a complex web of feedback systems that is still not wholly understood, making the treatment of any aspect insufficient. However, early targeting of key mediators of multiple elements may synergistically relieve symptoms . The peripheral parasympathetic nervous system, a bidirectional electrical and chemical signaling pathway that drives appetite, hunger, digestion, metabolism, immune activation, and other essential functions of the gastrointestinal system, may be such a target . The vagus nerve is the dominant electrical mediator of this system, with direct vagal innervation of the digestive tract and liver . The vagus plays key homeostasis-preserving roles in peripheral and central metabolic pathways, many of which are disrupted in CAC patients . The left and right vagus nerves asymmetrically innervate organs which play roles in essential gut-brain neural circuits, with the right vagus nerve primarily influencing gut-induced reward mechanisms, nutrient preference, and food memory. The vagus nerve’s role in multiple hallmark symptoms and mechanisms of CAC led us to hypothesize that dissecting its function in CAC may shed light on the consequent metabolic manifestations with implications for therapy.