Anorexia, sarcopenia, and cachexia are common complications of many chronic conditions including cancer, rheumatoid arthritis, HIV infection, aging, and chronic lung, heart, or kidney disease. Currently, there is no effective treatment for muscle atrophy or wasting conditions although they typically take a significant toll on the quality of life of patients and are associated with poor prognosis and decreased survival. Ghrelin affects multiple key pathways in the regulation of body weight, body composition, and appetite in the setting of cachexia that may lead to an increase in appetite and growth hormone secretion and a reduction in energy expenditure and inflammation. The net effect is increased lean body mass and fat mass preservation. In this chapter, we review the mechanisms of action of ghrelin and present the available data in animal models and human trials using ghrelin or ghrelin mimetics in different settings of cachexia.

Anorexia, meaning poor appetite, occurs in many human conditions, for example, anorexia nervosa, cachexia, and failure to thrive in infants. A key player in the regulation of appetite/food intake in general, as well as conditions of anorexia, is the hypothalamus, in particular, the AGRP/NPY and POMC/CART neurons in the arcuate nucleus. In this chapter, we review the hypothalamic aberrances seen in the anorectic anx/anx mouse. This mouse displays deviations in neuropeptidergic/-transmitter systems, including selective hypothalamic degeneration and inflammation that have been associated with mitochondrial dysfunction. In addition, we discuss data from other animal models, as well as clinical data relating hypothalamic inflammation/degeneration, neurogenesis, and mitochondrial dysfunction to conditions of disturbed regulation of food intake.

Ideal body weight for maximum life expectancy increases with advancing age. Older people, however, tend to weigh less than younger adults, and old age is also associated with a tendency to lose weight. Weight loss in older people is associated with adverse outcomes, particularly if unintentional, and initial body weight is low. When older people lose weight, more of the tissue lost is lean tissue (mainly skeletal muscle) than in younger people. When excessive, the loss of lean muscle tissue results in sarcopenia, which is associated with poor health outcomes. Unintentional weight loss in older people may be a result of protein-energy malnutrition, cachexia, the physiological anorexia of aging, or a combination of these. The physiological anorexia of aging is a decrease in appetite and energy intake that occurs even in healthy people and is possibly caused by changes in the digestive tract, gastrointestinal hormone concentrations and activity, neurotransmitters, and cytokines. A greater understanding of this decrease in appetite and energy intake during aging, and the responsible mechanisms, may aid the search for ways to treat undernutrition and weight loss in older people.

During the past decades, malnutrition has attracted increasing scientific attention and is by now regarded as a true geriatric syndrome characterized by multifactorial causality, identified by symptoms and accompanied by frailty, disability and poor outcome. This viewpoint summarizes our present knowledge and the usual current handling of malnutrition in older people and highlights the urgent need for action in this field. Age-related changes in the complex system of appetite regulation, resulting in the so-called anorexia of aging, predispose older adults to a decrease in food intake which may lead to malnutrition, if additional risk factors like health or social problems occur. Consequently, malnutrition is widespread in the older population, notably in those who are institutionalized. Despite the fact that effective interventions are available, prevention and treatment of malnutrition do not currently receive appropriate attention. As an important first step towards better awareness, screening for malnutrition should become a mandatory integral part of the comprehensive geriatric assessment. Furthermore, practical local guidelines should be implemented in all geriatric hospital wards and nursing homes in order to improve nutritional care in the daily routine. Important to note is that reasonable nutritional management is not possible without qualified staff in adequate numbers allowing appropriate individual nutritional care. Regarding future research, studies at the cellular, metabolic and clinical levels and the linking of information from different research approaches are required to better understand the transition from good nutritional health and independence of old people to malnutrition, functional impairment and poor health. In parallel to well-designed observational and intervention studies, standardized documentation of nutritional information in daily routine would enable the uniform collection of data for research as well as for political decisions. In summary, the time is ripe for better inclusion of nutrition in geriatric health care. This will not only bring about improved nutritional status and outcome, and thus individual benefit for the affected person, but also economic benefits both for the institution and the health-care system.

To analyze the clinical features and course of and to define the risk factors for bacterial meningitis in children.Retrospective study of 100 cases of bacterial meningitis in patients aged 0-18 years admitted to the Iasi Infectious Diseases Hospital between 2005 and 2010.We found a clear prevalence in male children (58%) from rural area (67%), with the highest incidence in the age group 2-5 years. A significant percentage of patients (43%) had previous hospitalization, condition which is known as predisposing factor for bacterial meningitis, the most common being ear infections (20%) and height and weight deficit (9%). 71% of patients were admitted within the first 48 h. The most common onset clinical manifestations were fever (84%), vomiting (70%), signs of meningeal irritation (59%), somnolence (23%), loss of appetite (19%), and coma in 5% of patients. In 36% of cases CSF was opalescent with moderate pleocytosis (35%); in 29% of patients CSF albumin level ranged between 0.7-1.0 g, the majority presenting normal glycorahia (71%). In only 21% of cases the microbial agent was identified (pneumococcal and meningococcal etiology, 8% and 6%, respectively). The course was generally favorable, and mortality rate was low (5%). Complications occurred in 3% of patients consisting in hydrocephalus and brain abscess.Bacterial meningitis remains a disease with potentially severe course. Clinical onset, most commonly atypical in children, requires differential diagnosis at the time of admission in order to initiate the most appropriate antibiotic therapy.

The mechanisms involved in anorexia in frail elderly people remain unclear. The objective of this study was to establish whether fasting and postprandial levels of gastrointestinal peptides, gastrointestinal motility, and hunger are modified by age and frailty.Three groups of subjects were studied: (a) frail elderly (>70 years) persons, (b) non-frail elderly (>70 years) persons, and (c) healthy adults (aged 25-65 years). After an overnight fast, participants ingested a 400 Kcal liquid meal and appetite, hormonal, and gastrointestinal responses were monitored during early (0-60 min) and late (60-240 min) postprandial periods.Frail persons showed poor nutritional status, sarcopenia, and almost absence of hunger during fasting and postprandial periods. Older persons presented higher levels of glucose and insulin during fasting, enhanced postprandial CCK release in early postprandial period and postprandial hyperglycemia and hyperinsulinemia, but similar ghrelin levels than younger adults. Ultrasound scan showed that the fasting antral area was higher and antral compliance lower in old persons. The paracetamol absorption test showed enhanced postprandial gastric emptying in the frail. Non-gallbladder contractors showed no CCK peak in younger and non-frail groups, but the same high CCK peak as contractors in the frail.Frailty was associated with anorexia, risk of malnutrition, and sarcopenia. Frail persons showed impaired gastric motility (larger antral area at rest, impaired antral compliance, and enhanced postprandial emptying), impaired gallbladder motility, and fasting and/or postprandial alterations in CCK, glucose, and insulin release. Further studies are needed to determine if these factors may contribute to anorexia of aging in frail persons.

The principal aims of the present study were to explore the prevalence of anorexia and the factors correlated to anorexia in a large population of older people living in nursing home. Secondary, we evaluated the impact of anorexia on 1-year survival.Data are from baseline evaluation of 1904 participants enrolled in the Un Link Informatico sui Servizi Sanitari Esistenti per l'Anziano study, a project evaluating the quality of care for older persons living in an Italian nursing home. All participants underwent a standardized comprehensive evaluation using the Italian version of the inter Resident Assessment Instrument Minimum Data Set (version 2.0) for Nursing Home. We defined anorexia as the presence of lower food intake. The relationship between covariates and anorexia was estimated by deriving ORs and relative 95% CIs from multiple logistic regression models including anorexia as the dependent variable of interest. Hazard ratios and 95% CIs for mortality by anorexia were calculated.More than 12% (240 participants) of the study sample suffered from anorexia, as defined by the presence of decreased food intake or the presence of poor appetite. Participants with functional impairment, dementia, behavior problems, chewing problems, renal failure, constipation, and depression, those treated with proton pump inhibitors and opioids had a nearly 2-fold increased risk of anorexia compared with participants not affected by these syndromes. Furthermore, participants with anorexia had a higher risk of death for all causes compared with nonanorexic participants (hazard ratio 2.26, 95% CI: 2.14-2.38).The major finding is that potentially reversible causes, such as depression, pharmacologic therapies, and chewing problems, were strongly and independently associated with anorexia among frail older people living in nursing home. Furthermore, anorexia was associated with higher rate of mortality, independently of age and other clinical and functional variables.

Anorexia nervosa (AN) is an eating disorder characterized by a decrease in caloric intake and malnutrition. It is associated with a variety of medical morbidities as well as significant mortality. Nutritional support is of paramount importance to prevent impaired quality of life later in life in affected patients. Some patients with restricting-type AN who are fully motivated to gain body weight cannot increase their food intake because of malnutrition-induced gastrointestinal dysfunction. Chronicity of AN prevents participation in social activities and leads to increased medical expenses. Therefore, there is a pressing need for effective appetite-stimulating therapies for patients with AN. Ghrelin is the only orexigenic hormone that can be given intravenously. Intravenous infusion of ghrelin is reported to increase food intake and body weight in healthy subjects as well as in patients with poor nutritional status. Here, we introduce the results of a pilot study that investigated the effects of ghrelin on appetite, energy intake, and nutritional parameters in five patients with restricting-type AN, who are fully motivated to gain body weight but could not increase their food intake because of malnutrition-induced gastrointestinal dysfunction.

Despite continuing improvements in our understanding of the causes of poor growth in chronic kidney disease, many unanswered questions remain: why do some patients maintain a good appetite whereas others have profound anorexia at a similar level of renal function? Why do some, but not all, patients respond to increased nutritional intake? Is feed delivery by gastrostomy superior to oral and nasogastric routes? Do children who are no longer in the 'infancy' stage of growth benefit from enteral feeding? Do patients with protein energy wasting benefit from increased nutritional input? How do we prevent obesity, which is becoming so prevalent in the developed world? This review will address these issues.

To investigate the level of anorexia and its correlation with mortality in chronic kidney disease stage 5 patients not yet on dialysis (CKD5-ND) and in those with stage 5 chronic kidney disease undergoing dialysis (CKD5-D).In an observational study, self-rated appetite (as part of a subjective global assessment of nutritional status), along with anthropometrics and biochemical markers of nutritional status, was analyzed in relation to survival. In a subgroup of patients, appetite change after start of dialysis was studied prospectively.Two hundred eighty CKD5-ND (40% female; age 54 ± 12 years; glomerular filtration rate 7 ± 2 mL/minute) and 243 CKD5-D patients (116 hemodialysis and 127 peritoneal dialysis [PD]; 44% female; age 54 ± 12 years; dialysis vintage time 12 ± 2 months) who had been on dialysis for about 1 year were studied.CKD5-ND patients with poor appetite (50%) had a higher prevalence of cardiovascular disease, lower body weight and serum creatinine level, and higher C-reactive protein. CKD5-D patients with poor appetite (33%) had impaired subjective global assessment of nutritional status and lower body weight, fat body mass, handgrip strength, hemoglobin, and serum albumin level. In a Kaplan-Meier analysis, appetite was not associated with survival difference, whereas in the Cox proportional hazards model with competing risk analysis, poor appetite increased mortality risk in PD patients but not in hemodialysis and CKD5-ND patients.In CKD5-ND patients, self-rated appetite was not an independent predictor of 48-months survival, whereas there was a significant increase in mortality risk in PD patients with poor appetite.