Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis.

Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.

Cancer cachexia: molecular mechanism and pharmacological management.

Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.

Poor Appetite Is Associated with Six Month Mortality in Hospitalised Older Men and Women.

OBJECTIVES: Appetite loss is common in hospitalised older individuals but not routinely assessed. Poor appetite in hospital has previously been identified as predictive of greater mortality in the six months following discharge in a single study of female patients. The present study aimed to assess this association in a larger sample including both hospitalised men and women. DESIGN: Longitudinal observational study with six month follow up. SETTING: Acute hospital wards in a single large hospital in England. PARTICIPANTS: Older inpatients aged over 70 years. MEASUREMENTS: Appetite was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ) during hospital stay. Deaths during six month follow-up period were recorded. Association between SNAQ score during hospital admission and death 6 months post-discharge was assessed using binary logistic regression in unadjusted and adjusted analysis. RESULTS: 296 participants (43% female, mean age 83 years (SD 6.9)) were included in this study. Prevalence of poor appetite (SNAQ score <14) was 41%. In unadjusted analysis a SNAQ score of <14 was associated with a 2.47 increase in odds of mortality at six months (OR 2.47 (95% CI 1.27,4.82)). This association remained after adjusting for number of comorbidities (Charlson index), length of stay and gender (OR 2.62 (95% CI 1.30, 5.27)). In unadjusted continuous analysis, every one point decrease in SNAQ score led to a 1.20 fold increase in odds of mortality at six months (OR 1.20 (95% CI 1.06-1.36)). This association remained in adjusted analysis (OR 1.22 (95% CI 1.07-1.39)). CONCLUSION: Poor appetite is common in hospitalised older people. We have confirmed the association, previously reported in older women, between poor appetite during hospital stay and greater mortality at six months post-discharge but in a larger study including older men and women. Further research is needed to understand the mechanisms of poor appetite, which lead to increased mortality.

Early recognition of anorexia through patient-generated assessment predicts survival in patients with oesophagogastric cancer.

Cancer cachexia is common in patients with oesophagogastric cancer (OG) and is linked to overall survival (OS). One of the key components of cachexia is anorexia; it is not known whether anorexia impacts on OS and there is no method of routine screening in current practice. Diagnosis relies on patients describing the symptoms, clinicians diagnosing anorexia and acting upon it. Patients with oesophageal/gastroesophageal junction or gastric cancer were assessed using the Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). FAACT A/CS includes 12 questions validated previously to diagnose anorexia in patients with cancer. Of the 182 patients included, 69% scored ≤37/48 and were considered to be anorexic; FAACT A/CS was a better predictor of OS in metastatic patients than body mass index or weight loss in the six months prior to cancer diagnosis. The median OS of patients with FAACT A/CS scores of >37 was longer than patients with scores of ≤37 (19.3 months vs 6.7 months, Hazard Ratio [HR] 2.9, 95% Confidence Interval [CI] 1.4-6.0, p<0.0001). Patients with performance status (PS) 0-2 and FAACT A/CS >37 had substantially longer OS than those with PS 0-2 and FAACT A/CS ≤37 (18.7 months vs 7.9 months, HR 2.5 (95% CI 1.2-5.1, P<0.0001). The FAACT A/CS questionnaire allows clinicians to identify patients with anorexia who may benefit from early nutrition interventions. Importantly, this is the first study to show the association between anorexia and survival in patients with metastatic OG cancers. This will form the basis of future interventional studies to improve patient outcomes.

Megestrol acetate for cachexia-anorexia syndrome. A systematic review.

In 1993, megestrol acetate (MA) was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with acquired immunodeficiency syndrome. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic, elderly, and acquired immunodeficiency syndrome patients is under investigation. This is an updated version of a Cochrane systematic review first published in 2005 and later updated in 2013 entitled 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. MA vs. placebo: in studies where MA was compared with placebo, the overall results showed that MA patients gained weight (mean difference, MD 2.25 kg, 95% CI [1.19, 3.3]) but did not gain quality of life (QOL) (standarized mean difference, SMD 0.5, 95% CI [-0.13, 1.13]), with more adverse events (relative risk, RR 1.46, 95% CI [1.05, 2.04]), but no difference in deaths (RR 1.26, 95% CI [0.70, 2.27]). MA vs. no treatment: MA patients gained weight (MD 1.45 kg, 95% CI [0.15, 2.75]) but did not gain QOL (standardized mean difference 3.89 95% CI [-14, 6.28]). There was no increase in adverse events (RR 0.90, 95% CI [0.39, 2.08]) or deaths (RR 1.01, 95% CI [0.42, 2.45]). MA vs. active drugs: MA patients gained weight (MD 2.5 kg, 95% CI [0.37, 4.64]) but did not gain QOL (MD 0.20 95% CI [-0.02, 0.43]) and did not report an increase in adverse events (RR 1.05 95% CI [0.95, 1.16]) or in deaths (RR 1.53, 95% CI [1.02, 2.29]) Different doses of MA: in studies where lower doses of MA were compared with higher doses of MA, we did not find differences either in weight gain (MD -0.94 kg, 95% CI [-3.33, 1.45]), QOL (MD 0.31 95% CI [-0.19, 0.81]), or adverse events (RR 1.34, 95% CI [0.65, 2.76]). Thus, we cannot reach a conclusion for an optimal dose of MA.

Role of nutrition on anemia in elderly.

Anemia in elderly population have a great incidence and is related to increased mortality risk. The incidence of nutrition in anemia is about one third of the total. Caloric and protein restriction, iron, vitamin B12, folic deficiency are the causes of nutritional anemia. Protein and energy malnutrition stimulate an increased cytokines production with induction of inflammation, immunodeficiency and anemia. Anorexia and obesity can be associated with anemia due to increased cytokines and hepdicin serum level. Macrophages activity is inhibited and a decrease in red blood cells (RBC), hemoglobin (Hb) concentration due to ineffective erythropoiesis is observed. An adequate energy and protein diet is necessary to reduce inflammation and increase iron absorption. A minimum of 1700 kcal/day and 1.7 gr/kg/day of protein intake are necessary to maintain anabolism in chronic patients to prevent and treat anemia. Iron supplementation by intravenous injection is safe and effective to correct severe iron deficiency. The supplementation of vitamins and oligomineral are useful to reduce oxidative stress and improve RBC longevity. Anemia in elderly could be prevented by an adequate nutrition, a simple and not expensive intervention, and associated to physical exercise reduce the incidence of mortality rate.

The ineffectiveness and unintended consequences of the public health war on obesity.

The public health war on obesity has had little impact on obesity prevalence and has resulted in unintended consequences. Its ineffectiveness has been attributed to: 1) heavy focus on individual-based approaches and lack of scaled-up socio-environmental policies and programs, 2) modest effects of interventions in reducing and preventing obesity at the population level, and 3) inappropriate focus on weight rather than health. An unintended consequence of these policies and programs is excessive weight preoccupation among the population, which can lead to stigma, body dissatisfaction, dieting, disordered eating, and even death from effects of extreme dieting, anorexia, and obesity surgery complications, or from suicide that results from weight-based bullying. Future public health approaches should: a) avoid simplistic obesity messages that focus solely on individuals' responsibility for weight and health, b) focus on health outcomes rather than weight control, and c) address the complexity of obesity and target both individual-level and system-level determinants of health.

Appetite predicts mortality in free-living older adults in association with dietary diversity. A NAHSIT cohort study.

This study aimed to assess the predictive ability of appetite for mortality among representative free-living Taiwanese older adults. A total of 1856 participants aged 65 years or over from the Elderly Nutrition and Health Survey during 1999-2000 completed an appetite question in a larger questionnaire. Personal information was obtained by face-to-face interview at baseline, together with a 24-hour dietary recall and simplified food frequency questionnaire which provided a dietary diversity score and food intake frequency. Survivorship was ascertained from the Death Registry until December 31, 2008. Participants with a poor appetite had lower dietary diversity scores (DDS) and intake frequencies of meat, fish and sea food, egg, vegetable and fruit intake, along with lower energy, protein, vitamin B-1, niacin, iron and phosphate intakes. Those who had fair and poor appetites had a higher risk of all-cause mortality compared to those with good appetite, with hazard ratios (HR) (95% confidence interval, CI) of 1.28 (1.03-1.58) and 2.27 (1.71-3.02), respectively. After adjustment for confounders, the HRs (95% CI) were 1.05 (0.83-1.33) and 1.50 (1.03-2.18), respectively. With further adjustment for DDS or general health these HRs became non-significant. The joint HR (95% CI) for "DDS ≤ 4 and poor appetite" was 1.77 (1.04-3.00) compared to "DDS > 4 and good appetite" as referent. Poor appetite is associated with lower food and nutrient intakes and an independent risk for mortality in older Taiwanese. In conclusion, appetite is separate, mediated by general health and modulated by dietary quality in its predictive capacity for mortality.

Heat-related deaths in Adelaide, South Australia: review of the literature and case findings - an Australian perspective.

Heat waves are not uncommon in Australia, but the event of 2009 was particularly severe and ranks third of the 21 recorded heat wave events in south-eastern Australia in terms of the resulting mortality and morbidity. This is a review of Coronial autopsy findings in South Australia (which has an area of nearly 1 million square kilometres with a population of 1.6 million that predominantly resides within the region of the capital: Adelaide) during the period of the 2009 heat wave. Fifty-four post-mortem examinations were performed on cases in which exposure to high ambient temperature was regarded as having caused or significantly contributed to the death. The findings (including results of toxicological and biochemical analyses, where available) are reviewed and compared with the post-mortem examination findings in 22 deaths over the same period not attributed to the effects of heat. There were no specific autopsy findings that distinguished heat-related from non heat-related deaths. The lack of specific post-mortem findings increases the reliance on scene investigation in order to be able to categorise a death as being heat-related. A checklist for scene investigators is proposed in order to assist with collection of relevant data to assist the Coronial investigation process.

Interleukin-6 but not tumour necrosis factor-alpha predicts survival in patients with advanced cancer.

PURPOSE: The purpose of this study was to evaluate the prognostic role of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the survival of patients with advanced cancer. METHODS: In this prospective cohort study between three hospice and palliative care centres in South Korea, we followed 98 advanced cancer patients until death or the end of the study. Approximately 60 % of the patients had poor functional status (Eastern Cooperative Oncology Group score ≥3). We investigated the symptoms of cancer cachexia anorexia syndrome, possible cytokine-related confounders such as infection and medication records. Influence from clinical variables was adjusted using the Cox proportional hazard model. RESULTS: The median survival time was 27 days. On multivariate analysis, elevated IL-6 (hazard ratio, 2.139; p = 0.003) was found to be an independent significant prognostic factor. TNF-α was not a significant factor. Poor performance status and male gender were also independently related to shortened survival. CONCLUSIONS: IL-6 level can be a useful indicator of survival time of patients with advanced cancer at the very end of life. In contrast, the prognostic role of TNF-α requires further study.

The anorexia of ageing: physiopathology, prevalence, associated comorbidity and mortality. A systematic review.

The physiological processes of ageing and factors prevalent in the elderly such as comorbidities and polypharmacy often cause loss of appetite in the elderly, which we call anorexia of ageing. Social factors, together with changes in the sensory organs, can be important causes of a reduction in both appetite and ingestion. This review assesses the regulation of appetite in the elderly and the development of anorexia of ageing. It also examines the prevalence of this type of anorexia, its associated comorbidities and mortality rates. We have reviewed 27 studies, with a total of 6208 patients. These reported changes in the secretion and response of both central and peripheral hormones that regulate appetite. Anorexia, very prevalent among hospitalized and institutionalized elderly people, is associated with comorbidity and represents a predictive factor for mortality. No treatment for it has been proved to be effective. The mechanism regulating ingestion in elderly people is complex and difficult to resolve. Comorbidity as a cause or a consequence of anorexia of ageing has become a research field of great interest in geriatrics. A correct nutritional evaluation is a fundamental part of an integrated geriatric assessment.

Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice.

Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia, hyperactivity, and fear of weight gain. No approved pharmacological treatments exist for AN despite high mortality rates. The activity-based anorexia (ABA) phenomenon models aspects of AN in rodents, including progressive weight loss, reduced food intake, and hyperactivity. First, we optimized the ABA paradigm for mice. We compared mouse strains (Balb/cJ, A/J) for susceptibility with ABA, and evaluated the effects of different food access durations (2, 4, 6, 8, and 10 h) on ABA parameters. Balb/cJ mice exhibited significantly shorter survival time (days until 25% bodyweight loss) in the ABA paradigm compared with A/J mice. Furthermore, 6 h of food access reduced survival in mice housed with wheels without reducing survival in mice housed without wheels. We then evaluated the effects of chronic treatment with fluoxetine (4 weeks) or subchronic treatment with olanzapine (OLZ) (1 week) on ABA in BALB/cJ mice. OLZ (12 mg/kg/day) significantly increased survival and reduced food anticipatory activity (FAA). However, OLZ did not alter food intake or running wheel activity during ad-lib feeding (baseline) or restriction conditions, or in mice housed without wheels. Fluoxetine (18 mg/kg/day) increased food intake and reduced FAA, but did not alter survival. Here, we report for the first time that OLZ, but not fluoxetine, reduces ABA in mice. Our findings indicate further need for clinical investigations into the effects of OLZ, but not selective serotonin reuptake inhibitors, on core features of AN.

Effects of anorexia on mortality among older adults receiving home care: an observation study.

PURPOSE: We describe the prevalence of secondary anorexia in a population of older people living in community and receiving home care. In addition, we examined the relationship between secondary anorexia and mortality. METHODS: We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, that collected data on patients admitted to home care programs. A total of twelve Home Health Agencies participated in such project evaluating the implementation of the Minimum Data Set for Home Care (MDS-HC) instrument. A total of 2757 patients were enrolled in the present study. The main outcome measures were the prevalence of anorexia, weight loss and survival. RESULTS: More than 25% (744 subjects) of the study sample suffered from anorexia. During a mean follow-up of 10 months from initial MDS-HC assessment, 468 patients (17%) died. There was uneven distribution of the risk. After adjusting for age, gender and for all other possible risk factors for death (living alone, physical and cognitive disability, behavior problems, urinary incontinence, pressure ulcer, hearing impairment, congestive heart failure, hypertension, depression, diabetes, renal failure, cancer), subjects with anorexia were more likely to die relative to patients without anorexia (RR, 1.83; 95% CI 1.45-2.31). Even though the risk of mortality was higher among subjects suffering from anorexia and weight loss, the anorexia per se was associated with higher risk compared with subjects without anorexia (RR, 1.45; 95% CI 1.01-2.19). CONCLUSIONS: Anorexia is associated with a significant higher risk of all-cause mortality. The present findings support the possibility that anorexia has an independent effect on survival even among old people receiving home care.

Canine tonsillar squamous cell carcinoma -- a multi-centre retrospective review of 44 clinical cases.

OBJECTIVES: To review the presenting clinical signs, treatment and survival of dogs with tonsillar squamous cell carcinoma and, if possible, to identify useful prognostic indicators. METHODS: Medical records of 44 dogs were reviewed retrospectively. Clinical signs, clinical stage, time of diagnosis, treatment and outcome were recorded. Data were analysed using the Kaplan-Meier, log-rank, Student's t test, Kruskal-Wallis test and Chi-square/Fisher Exact test as appropriate. RESULTS: The most frequent clinical signs were cough (12 dogs, 27%), enlarged lymph nodes (11 dogs, 25%) and dysphagia (11 dogs, 25%). Anorexia and lethargy were less common but were significantly associated with a poor outcome. No matter what treatment modalities were used, survival times were short and median survival time for all the dogs in the study was 179 days. However, there were a small number of long-term survivors. CLINICAL SIGNIFICANCE: Dogs with tonsillar squamous cell carcinoma that suffered anorexia and lethargy had shorter survival times than patients without these clinical signs. Although surgery, chemotherapy and radiotherapy seem to increase the median survival time of dogs diagnosed with tonsillar squamous cell carcinoma, there is no highly effective treatment for canine tonsillar squamous cell carcinoma.

Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival.

Cancer anorexia-cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut-brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia-cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia-cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia-cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia-cachexia.

Cancer cachexia.

PURPOSE OF REVIEW: Although cachexia has a major effect on both the morbidity and mortality of cancer patients, information on the mechanisms responsible for this condition is limited. This review summarizes recent data in this area. RECENT FINDINGS: Cachexia is defined as loss of muscle, with or without fat, frequently associated with anorexia, inflammation and insulin resistance. Loss of adipose mass is due to an increased lipolysis through an increased expression of hormone-sensitive lipase. Adipose tissue does not contribute to the inflammatory response. There is an increased phosphorylation of both protein kinase R (PKR) and eukaryotic initiation factor 2 on the alpha-subunit in skeletal muscle of cachectic cancer patients, which would lead to muscle atrophy through a depression in protein synthesis and an increase in degradation. Mice lacking the ubiquitin ligase MuRF1 are less susceptible to muscle wasting under amino acid deprivation. Expression of MuRF1 and atrogin-1 is increased by oxidative stress, whereas nitric oxide may protect against muscle atrophy. Levels of interleukin (IL)-6 correlate with cachexia and death due to an increase in tumour burden. Ghrelin analogues and melanocortin receptor antagonists increase food intake and may have a role in the treatment of cachexia. SUMMARY: These findings provide impetus for the development of new therapeutic agents.

Senile anorexia in acute-ward and rehabilitations settings.

UNLABELLED: The most common pathological change in eating behaviour among older persons is anorexia, which accounts for a large percent of undernutrition in older adults. The main research aims are to determine, in a sample of acute and rehabilitation elderly subjects, the prevalence of anorexia of aging and the causes most impacting on senile anorexia. METHODS: four different Units cooperated to this research study. Patients were recruited from geriatric acute and rehabilitation wards in Italy. Each Research Unit, for the estimation of the prevalence of anorexia in elderly subjects evaluated all the patients aged over 65 recruited from April 2006 to June 2007. Nutritional status, depression, social, functional and cognitive status, quality of life, health status, chewing, swallowing, sensorial functions were evaluated in anorexic patients and in a sample of "normal eating" elderly subjects. RESULTS: 96 anorexic subjects were selected in acute and rehabilitation wards (66 women; 81.5 +/- 7 years; 30 men: 81.8 +/- 8 years. The prevalence of anorexia in the sample was 33.3% in women and 26.7% in men. Anorexic subjects were older and more frequently needed help for shopping and cooking. A higher (although not statistically significant) level of comorbidity was present in anorexic subjects. These subjects reported constipation and epigastrium pain more frequently. Nutritional status parameters (MNA, anthropometry, blood parameters) were significantly worst in anorexic subjects whereas CRP was higher. Chewing and swallowing efficiencies were significantly impaired and eating patterns were different for anorexic subjects with a significant reduction of protein rich foods. CONCLUSIONS: consequences of anorexia can be extremely serious and deeply affect both patient's mobility, mortality and quality of life. Therefore, it is of utmost importance to perform a special evaluation of the nutritional risk, to constantly evaluate the nutritional status and feeding intake of older patients, to identify and treat the underlying disease when possible, to institute environmental and behavioural modifications, to organise staff better in order to produce higher quality feeding assistance during mealtimes, to plan early nutrition rehabilitation and nutritional education programs for caregivers. There is also the necessity to develop diagnostic procedures easy to perform, able to identify the pathogenesis of anorexia and, therefore, treatment strategies exactly fitting the patients' needs.

A retrospective study of the association between megestrol acetate administration and mortality among nursing home residents with clinically significant weight loss.

BACKGROUND: Megestrol acetate (MA) is a progestin widely used to treat weight loss and cachexia in patients suffering from AIDS or cancer. Although MA is also frequently prescribed for similarly malnourished elderly individuals, the efficacy and morbidity of MA treatment in this patient population remain unclear. OBJECTIVE: The goal of this study was to examine the effects of MA therapy on weight and overall mortality in elderly nursing home residents. METHODS: This was a case-control cohort study of 17,328 nursing home residents admitted to Beverly Healthcare nursing home between January 1, 2000, and December 31, 2003, who had lost either 5% of total body weight within 3 months or 10% of total body weight within 6 months. Residents within this weight loss group who received MA therapy--within 30 days of their weight loss documentation--were matched (1:2) with non-MA-treated residents with respect to age, sex, race, weight, and first notation of weight loss. Residents were further matched by propensity score for activities of daily living, cognitive functioning, number of medications taken during the 7 days before data entry, clinical condition (unstable, acute episode of a recurrent problem, end-stage disease), cancer diagnosis, and human immunodeficiency virus diagnosis. RESULTS: A total of 709 patients (mean [SD]age, 84.1 [9.7]years; 70.9% female) who received MA therapy were matched with 1418 non-MA-treated patients (mean [SD] age, 84.2 [9.0] years; 70.9% female). Of the 709 MA patients, 281 (39.6%) were alive and in the nursing home at last follow-up, 149 (21.0%) were alive and discharged to another facility or to home, and 279 (39.4%) died in the nursing home. For the controls, 651 (45.9%) were alive and in the nursing home, 308 (21.7%) were discharged to another facility or to home, and 459 (32.4%) died in the nursing home. The median survival of MA-treated residents (23.9 months; 95% CI, 20.2-27.5) was significantly less than untreated residents (31.2 months; 95% CI, 27.8-35.9) (P < 0.001). Median weight and median of weight differences were unchanged after 6 months of treatment with MA compared with matched controls. CONCLUSIONS: MA treatment of elderly nursing home residents with significant weight loss was associated with a significant increase in all-cause mortality without a significant increase in weight. Randomized, prospective studies of the use of MA in elderly nursing home residents are necessary to more fully evaluate morbidity and mortality associated with this therapy.

Nutritional treatment of cancer cachexia in rats. Use of a diet formulated with a crayfish enzymatic extract.

BACKGROUND: Terminal cancer-associated cachexia, characterized by a marked weight loss, anorexia, asthenia and anemia, is usually associated with a malnutrition status. AIM OF THE STUDY: To investigate whether a diet formulated with a crayfish enzymatic extract, enriched in essential amino acids, omega-3 fatty acids, and astaxanthin, would be effective for the treatment of cancer-associated cachexias, by decreasing mortality and morbidity rates in cachectic rats and/or improving survival. METHODS: Two types of diet were used: a standard diet and one formulated with crayfish enzymatic extract. Rats were divided into two groups (24 animals per group): one without tumor (T-) and the other with tumor (T+) (AH-130 Yoshida ascites hepatoma). Each group was further divided into two subgroups (12 animals per subgroup). Two subgroups (T-(standard) and T+(standard)) were fed the standard diet and the other two (T-(CFEE) and T+(CFEE)) the crayfish enzymatic extract one for four weeks, after which different tissue and plasma parameters were studied. RESULTS: The implantation of the tumor resulted in a considerable loss of muscle and adipose tissue mass in both groups, but the loss of muscle and fat was lower in the group fed the crayfish enzymatic extract diet. There was also a concomitant increase in the plasma concentration of TNF-alpha, although the increase was smaller in the crayfish enzymatic extract-treated group. CONCLUSION: This study shows that although the treatment of cachetic rats with the crayfish enzymatic extract diet did not revert the cachexia, it increased survival (57.1% vs. 25.9% in the group treated with crayfish enzymatic extract and standard diets, respectively) and meliorated the cachexia symptoms--anorexia and body mass loss (muscle and adipose tissue).