Influence of pretreatment quality of life on prognosis in patients with urothelial carcinoma.

BACKGROUND: We investigated the association between the pretreatment quality of life (QOL) and overall survival (OS) in patients with urothelial carcinoma (UC), as the influence of pretreatment QOL on prognosis remains unclear in patients with localized and metastatic UC. METHODS: Between June 2013 and May 2019, we retrospectively investigated 205 patients with UC who received radical cystectomy or nephroureterectomy for non-metastatic UC (M0 group) or systemic chemotherapy for metastatic UC (M1 group). Patients answered the European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (QLQ-C30) before the treatments. Patients were stratified into two groups: QOL high and low according to the optimal cutoff scores which were defined by receiver operating characteristic curve. Inverse probability of treatment weighting (IPTW)-adjusted multivariate Cox regression analyses were performed to investigate the clinical implication of pretreatment QOL score on OS in patients with UC. RESULTS: The number of patients in the M0 and M1 groups was 125 and 80, respectively. Optimal cutoff values in global, fatigue, pain, appetite loss, physical, and role scores were < 50, > 33, > 33, > 16, < 80, and < 67, respectively. IPTW-adjusted multivariate Cox regression analyses revealed that appetite loss score indicated a significantly poorer OS in the M1 group. No significant association of QOL with OS was observed in the M0 group. CONCLUSION: Pretreatment QOL of appetite loss may predict poor prognosis of patients with metastatic UC.

Appetite loss as a potential predictor of suicidal ideation and self-harm in adolescents: A school-based study.

Suicide is a leading cause of death in adolescents, but detection of its risk is often challenging. Many mental illnesses share the common symptom of appetite loss and it is also known that people who suffer from these illnesses are at greater risk of suicide. However, the relationship between appetite loss and suicide risk has yet to be examined. For adolescents in particular, questions about appetite loss may be easier to answer than sensitive questions regarding mental health. The present study aims to investigate the association of appetite loss with suicidal ideation and self-harm in adolescents. Rates of adolescents with suicidal ideation or self-harm associated with appetite-loss were examined in 18,250 Japanese junior and senior high school students (aged 12-18) using a self-report questionnaire. Insomnia, a physical symptom which has previously been associated with suicide risk, was also controlled for in the analysis. Results showed that rates of adolescents with suicidal ideation or self-harm significantly increased according to the degree of self-reported appetite loss. Similar results were observed for insomnia. Odds ratios (ORs) for suicidal ideation and self-harm were 5.5 and 4.1 for adolescents with appetite loss compared to those without it, and the ORs were 5.5 and 3.5 for those with insomnia compared to those without it, respectively, adjusting for sex and age (p < 0.001). ORs remained statistically significant after adjusting for depression/anxiety (General Health Questionnaire-12 score). In conclusion, self-reported appetite loss was highly associated with suicidal ideation and self-harm in adolescents; adolescents reporting physical symptoms such as loss of appetite or insomnia should be given careful attention.

Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes.

OBJECTIVE: Identify depression symptoms during active late-life depression (LLD) that predict conversion to dementia. METHODS: The authors followed a cohort of 290 participants from the Neurocognitive Outcomes of Depression in the Elderly study. All participants were actively depressed and cognitively normal at enrollment. Depression symptom factors were derived from prior factor analysis: anhedonia and sadness, suicidality and guilt, appetite and weight loss, sleep disturbance, and anxiety and tension. Cox regression analysis modeled time to Alzheimer disease (AD) and non-AD dementia onset on depression symptom factors, along with age, education, sex, and race. Significant dementia predictors were tested for interaction with age at depression onset. RESULTS: Higher scores on the appetite and weight loss symptom factor were associated with an increased hazard of both AD and non-AD dementia. This factor was moderated by age at first depression onset, such that higher scores were associated with higher risk of non-AD dementia when depression first occurred earlier in life. Other depression symptom factors and overall depression severity were not related to risk of AD or non-AD dementia. CONCLUSION: Results suggest greater appetite/weight loss symptoms in active episodes of LLD are associated with increased likelihood of AD and non-AD dementia, but possibly via different pathways moderated by age at first depression onset. Results may help clinicians identify individuals with LLD at higher risk of developing AD and non-AD dementia and design interventions that reduce this risk.

Appetite loss and neurocognitive deficits in late-life depression.

OBJECTIVES: This study aimed to examine the association of appetite loss symptoms to neurocognitive performance in late-life depression (LLD). METHODS: This study used cross-sectional data from individuals aged 60+ years with major depressive disorder (N = 322). Participants received clinical assessment of depression and neuropsychological testing. Factor analysis was used to characterize depression symptom factors, and composite scales were developed for episodic memory, psychomotor-executive functions, verbal fluency, and working memory span. RESULTS: Factor analysis produced a five-factor solution: (1) anhedonia/sadness; (2) suicidality/guilt; (3) appetite/weight loss; (4) sleep disturbance; and (5) anxiety/tension. In separate multivariate models for each neurocognitive domain and including all five depression factors, higher appetite-loss-related symptoms were associated with lower performance in episodic memory, psychomotor-executive functions, and verbal fluency; results were significant with covariates of age, education, race, sex, age of depression onset, and illness burden. No other depression factors were associated with neurocognitive performance in these models. In an additional set of models, the appetite factor mediated the association between global depression severity and neurocognitive performance. DISCUSSION: A factor of appetite and weight loss symptoms in LLD was uniquely associated with neurocognitive performance, in contrast to lack of association among other depression symptom factors. CONCLUSION: Cognitive deficits are a major adverse outcome of LLD, and prominent appetite loss during acute depression may be a marker for these deficits, independent of overall depression severity. Research is needed to understand the mechanisms that may explain this association, and how it is related to the cognitive and symptomatic course of LLD.

Cancer cachexia pathophysiology and translational aspect of herbal medicine.

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. In particular, tumor necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a depression in protein synthesis, an increase in protein degradation or a combination of both. Cancer patients suffer from the reduction in physical function, tolerance to anti-cancer therapy and survival, while many effective chemotherapeutic agents for cancer are burdened by toxicities that can reduce patient's quality of life or hinder their effective use. Herbal medicines have been widely used to help improve such conditions. Recent studies have shown that herbal medicines such as rikkunshito enhance ghrelin signaling and consequently improve nausea, appetite loss and cachexia associated with cancer or cancer chemotherapy, which worsens the quality of life and life expectancy of the patients. The multicomponent herbal medicines capable of targeting multiple sites could be useful for future drug discovery. Mechanistic studies and identification of active compounds could lead to new discoveries in biological and biomedical sciences.

Association of anorexia/appetite loss with malnutrition and mortality in older populations: A systematic literature review.

Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore, we performed a systematic literature review to assess the morbidity and mortality burden of anorexia/appetite loss in older populations. Following PRISMA guidelines, searches were run (1 January 2011 to 31 July 2021) in PubMed, Embase® and Cochrane databases to identify English language studies of adults aged ≥ 65 years with anorexia/appetite loss. Two independent reviewers screened titles, abstracts and full text of identified records against pre-defined inclusion/exclusion criteria. Population demographics were extracted alongside risk of malnutrition, mortality and other outcomes of interest. Of 146 studies that underwent full-text review, 58 met eligibility criteria. Most studies were from Europe (n = 34; 58.6%) or Asia (n = 16; 27.6%), with few (n = 3; 5.2%) from the United States. Most were conducted in a community setting (n = 35; 60.3%), 12 (20.7%) were inpatient based (hospital/rehabilitation ward), 5 (8.6%) were in institutional care (nursing/care homes) and 7 (12.1%) were in other (mixed or outpatient) settings. One study reported results separately for community and institutional settings and is counted in both settings. Simplified Nutritional Appetite Questionnaire (SNAQ Simplified, n = 14) and subject-reported appetite questions (n = 11) were the most common methods used to assess anorexia/appetite loss, but substantial variability in assessment tools was observed across studies. The most commonly reported outcomes were malnutrition and mortality. Malnutrition was assessed in 15 studies, with all reporting a significantly higher risk of malnutrition in older individuals with anorexia/appetite loss (vs. without) regardless of country or healthcare setting (community n = 9, inpatient n = 2, institutional n = 3, other n = 2). Of 18 longitudinal studies that assessed mortality risk, 17 (94%) reported a significant association between anorexia/appetite loss and mortality regardless of either healthcare setting (community n = 9, inpatient n = 6, institutional n = 2) or method used to assess anorexia/appetite loss. This association between anorexia/appetite loss and mortality was observed in cohorts with cancer (as expected) but was also observed in older populations with a range of comorbid conditions other than cancer. Overall, our findings demonstrate that, among individuals aged ≥ 65 years, anorexia/appetite loss is associated with increased risk of malnutrition, mortality and other negative outcomes across community, care home and hospital settings. Such associations warrant efforts to improve and standardize screening, detection, assessment and management of anorexia/appetite loss in older adults.

Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma.

Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC.

Assessment and Management of Appetite Loss in Older Adults: An ICFSR Task Force Report.

The Appetite loss in older people is an important unmet clinical need in geriatrics. The International Conference on Frailty and Sarcopenia Research (ICFSR) organized a Task Force on April 20th 2022, in Boston, to discuss issues related to appetite loss in older people, in particular, the assessment tools currently available, its evaluation in the primary care setting, and considerations about its management. There is a high heterogeneity in terms of the etiology of appetite loss in older people and a gold standard assessment tool for evaluating this condition is still absent. Although this may render difficult the management of poor appetite in clinical practice, validated assessment tools are currently available to facilitate early identification of appetite loss and support care decisions. As research on biomarkers of appetite loss progresses, assessment tools will soon be used jointly with biomarkers for more accurate diagnosis and prognosis. In addition, efforts to foster the development of drugs with a favorable risk/benefit ratio to combat poor appetite should be strengthened.

Association between Survival Duration of Older Patients with Advanced Unresectable Pancreatic Cancer and Appetite Loss: A Retrospective Cohort Study.

This retrospective cohort study clarified associations between trajectories in palliative care and appetite loss among older patients with advanced unresectable pancreatic cancer and reviewed pancreatic cancer diagnosis among these populations in rural community hospitals. Patients aged >65 years and with pancreatic cancer in a rural community hospital were enrolled. The primary outcome was survival duration from the time of pancreatic cancer diagnosis. Participants were divided into those with and without appetite loss. Cumulative event-free survival rates were calculated using the Kaplan−Meier method, analyzed using the log-rank test, and stratified by factors with statistically significant between-group differences (serum albumin). The mean participant age was 84.14 (SD, 8.34) years; 31.4% were men. Significant between-group differences were noted in albumin concentration and survival duration. Kaplan−Meier curves showed a significant between-group difference in survival probability (p < 0.001). Survival duration significantly differed after stratification by albumin level (p < 0.001). Appetite loss may be a useful symptom for predicting mortality among older patients with unresectable pancreatic cancer, and hypoalbuminemia may accelerate deterioration in their conditions. Accordingly, subjective appetite loss observed by patients and families should be assessed to predict mortality, and it is advisable for physicians to promptly discuss relevant and advanced directives at appropriate timings.

The association between appetite loss, frailty, and psychosocial factors in community-dwelling older adults adults.

BACKGROUND: Appetite loss (AL) in older adults can reduce energy and nutrient intake, increasing the risk of weight loss, sarcopenia, frailty, and ultimately, mortality. The identification of associated factors to AL is important to plan different interventions. AIMS: To identify the association between appetite loss, frailty, and psychosocial factors in community-dwelling older adults. METHODS: Cross-sectional analysis of the cohort study MiMiCS-FRAIL based in Jundiai City, São Paulo, Brazil. Patients 60+ years old were evaluated from January 2019 to August 2020. The AL (dependent variable) was evaluated through the SNAQ questionnaire; the independent variables were: frailty (identified by frailty index-36; FI-36) which is based on the accumulation of deficits; depressive symptoms (GDS scale); ethnicity, and years of formal schooling, both used as proxies of socioeconomic status. The associations were investigated using logistic regression models (crude and multiple). MAIN RESULTS: The final sample included 122 older adults, 58.2% of women, mean age of 71.7 years, 80.3% White, and low educational level (5.8 ± 4.3 years of formal schooling). We found 19.6% of the sample presenting AL. The final regression models showed independent and significant association between AL and age (OR = 1.11; 95%IC = 1.03-1.20; p < 0.01), being non-White (OR = 6.47; 95%IC = 1.63-25.58; p < 0.01), and presence of depressive symptoms (OR = 8.38; 95%IC = 2.31-30.47; p < 0.01). However, years of formal schooling, gender, and FI-36 remained statistically non-significant in the model. CONCLUSION: Our data pointed to the presence of depressive symptoms and social variables as significant factors associated with AL. Further studies with more robust samples or longitudinal design will clarify some unanswered questions of our study.

Factors related to malnutrition and their association with frailty in community-dwelling older adults registered at a geriatric clinic.

BACKGROUND: We hypothesized that factors related to malnutrition, namely low muscle mass, appetite loss, and adiposity, are associated with frailty and pre-frailty in community-dwelling older adults. AIMS: To identify the prevalence of frailty and pre-frailty in a Brazilian convenience sample and test the association between these conditions and malnutrition-related factors. METHODS: This is a cross-sectional analysis of an ongoing community project. We studied 106 older adults (≥60 years old). Frailty (dependent variable) was screened using the FRAIL-BR scale. The independent variables were appetite loss (AL), screened from the SNAQ questionnaire; sarcopenia risk, investigated by SARC-F; body adiposity, estimated by the body mass index (BMI); visceral adiposity, estimated by waist circumference (WC) and the combination of these two indicators. The associations were investigated using multinomial logistic regression models. MAIN RESULTS: We found, from our sample, 30.2 % pre-frail and 31.1 % frail participants. The frail and pre-frail were older than the non-frail; the frail ones presented a higher proportion of sarcopenia risk and a higher proportion of AL. From the multiple regression models, frailty conditions showed significant association with the AL (OR = 0.68; p = 0.012 and OR = 0.64; p = 0.009 for pre-frail and frail, respectively) and with sarcopenia risk (OR = 3.24; p = 0.001 and OR = 5.34; p < 0.011 for pre-frail and frail respectively). The adiposity indicated by waist circumference, and age, remained in the final model only as adjusting variables but without statistical significance. CONCLUSIONS: in our convenience sample of older adults, frailty and pre-frailty showed significant association with appetite loss and sarcopenia risk, but not with adiposity indicators. Future studies are needed to better understand our findings.

Brain MRI detection of early Wernicke's encephalopathy in a hemodialysis patient.

A 93-year-old hemodialysis patient became hospitalized for thiamine deficiency-induced appetite loss and ultimately experienced consciousness disorder diagnosed as Wernicke's encephalopathy (WE). Since brain MRI on admission was retrospectively found to display faint WE findings, careful brain MRI assessment is recommended in hemodialysis patients with appetite loss alone.

Association between transient appetite loss and vitamin B1 deficiency in elderly patients with suspected deficiency.

BACKGROUND: There is scarce evidence associating vitamin B1 levels and appetite loss duration in elderly patients with suspected B1 deficiency. We aimed to investigate this association in elderly hospitalized patients with suspected vitamin B1 deficiency in rural Japan. METHODS: This cross-sectional study evaluated 309 elderly patients (aged ≥ 65 years) admitted to one rural Hospital between April 2017 and March 2019. We collected data on vitamin B1 level, age, sex, body mass index, albumin levels, area of residence, long-term care, dependent conditions, activities of daily living, Charlson comorbidity index, and appetite loss from the patients' electronic medical records. Vitamin B1 deficiency was defined as serum vitamin B1 levels <20 µg/dL. Data were analyzed using the Mann-Whitney U, Student's t, and chi-square tests, followed by multivariable logistic regression, to examine the association between vitamin B1 deficiency and appetite loss. RESULTS: Eighty-eight (28.5%) patients had vitamin B1 deficiency. In multivariable logistic regression, appetite loss (for both < 1 and > 1 week) before admission to the hospital showed a significant association with vitamin B1 deficiency (adjusted odds ratio [AOR] =10.80, 95% confidence interval [CI]: 5.16-22.00, P < .001; and AOR = 5.77, 95% CI: 2.88-11.50, P < .001, respectively). CONCLUSIONS: Appetite loss is associated with vitamin B1 deficiency in elderly Japanese patients living in rural areas. Therefore, physicians should be aware of the possibility of vitamin B1 deficiency in elderly patients with appetite loss and focus on early intervention.

Development of a simple and valid nutrition screening tool for pediatric hospitalized patients with acute illness.

Background: Nutritional screening, intervention and assessment in patients with undernutrition are key components of any nutritional care. The goal of any nutritional assessment is to determine the specific nutritional risk(s). Presently, there are no guidelines on any ideal screening tool to be used on admission for identification of children that are at risk of developing malnutrition during their hospital stay. The objective of the study was to develop a valid and simple nutritional screening tool which can be used on hospital admission to identify pediatric patients at risk of malnutrition .Methods: This study was cross sectional analytical that enrolled children (n:161) admitted with acute illness to the general wards at Cairo University Children Hospitals (CUCH). The answers to the developed questionnaire were compared to the Subjective Global Assessment (SGA), those with high accuracy (≥80%) were used for validity with anthropometric measures. Results: In the 'less than two years of age' group, the simple and valid nutritional screening tools were the following questions: (Is there a problem during breast-feeding?), (Is there scanty breast milk?), (Is there appetite loss?). The simple and valid nutritional screening tools during the 'early childhood' group were the following questions: (Is there appetite loss?), (Is there any skipping of meals?), (Are they watching TV, videotapes and/or playing computer games for more than two hours/day?). The simple and valid  nutritional screening tools during the 'late childhood' group were the following questions: (Is there appetite loss?), (Are they watching TV, videotapes and/or playing computer games for more than two hours/day?). Conclusion: The simple and valid nutritional screening tools differ according to age groups. The one which is valid in all ages is the question about the appetite loss.

Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model.

Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks-(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice.

The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study.

Background: Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients. Methods: The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline. Results: Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients' self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated. Conclusions: Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.

Association Between Single Nucleotide Polymorphisms in PPARA and EPAS1 Genes and High-Altitude Appetite Loss in Chinese Young Men.

Appetite loss is a common symptom that occurs in high altitude (HA) for lowlanders. Previous studies indicated that hypoxia is the initiating vital factor of HA appetite loss. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 play important roles in hypoxic responses. We aimed to explore the association of these hypoxia-related gene polymorphisms with HA appetite loss. In this study, we enrolled 416 young men who rapidly ascended to Lhasa (3700 m) from Chengdu (<500m) by plane. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 were genotyped by MassARRAY. Appetite scores were measured to identify HA appetite loss. Logistic regression and multiple genetic models were tested to evaluate the association between the single nucleotide polymorphisms (SNPs) and risk of HA appetite loss in crude and adjusted (age and SaO2) analysis. Subsequently, Haploview software was used to analyze the linkage disequilibrium (LD), haplotype construction and the association of diverse haplotypes with the risk of HA appetite loss. Our results revealed that allele "A" in PPARA rs4253747 was significantly associated with the increased risk of HA appetite loss. Codominant, dominant, recessive, and log-additive models of PPARA rs4253747 showed the increased risk of HA appetite loss in the crude and adjusted analysis. However, only dominant, overdominant, and log-additive models of EPAS1 rs6756667 showed decreased risk of HA appetite loss in the crude and adjusted analysis. Moreover, the results from haplotype-based test showed that the rs7292407-rs6520015 haplotype "AC" was associated with HA appetite loss in the crude analysis rather than the adjusted analysis. In this study, we first established the association of SNPs in PPARA (rs4253747) and EPAS1 (rs6756667) genes with susceptibility to HA appetite loss in Han Chinese young men. These findings provide novel insights into understanding the mechanisms involved in HA appetite loss.

Aging-related anorexia and its association with disability and frailty.

BACKGROUND: Anorexia of ageing may be a precursor to various geriatric syndromes. We elucidated whether anorexia of ageing had a significant impact on incident disability and investigated whether anorexia of ageing had a direct association with future disability or an indirect association with disability via frailty. METHODS: This study employed an observational, longitudinal, cohort design in a community setting. Participants were 4393 older adults (75.9 ± 4.3 years). Anorexia of ageing was assessed by a simplified nutritional appetite questionnaire. Frailty was operationalized as slowness, weakness, exhaustion, low physical activity, and weight loss. Participants who had none of these characteristics were considered robust, those with one or two characteristics were considered pre-frail, and those with three or more characteristics were considered frail. We examined sociodemographic variables (age, sex, and education), medical history (medication and chronic disease history), lifestyle factors (smoking and drinking habits and living arrangement), body mass index, blood nutrition data, depressive symptoms, physical functioning, and cognitive functioning. RESULTS: The prevalence of anorexia of ageing was 10.7% (n = 468). The proportion of physical frailty, pre-frailty, and robustness were 8.4, 52.0, and 39.6%, respectively, in the without anorexia of ageing group, and 20.3, 57.7, and 22.0%, respectively, in the anorexia of ageing group (P < 0.001). During a 2-year follow-up, the prevalence proportion of disability was 5.6% in the without anorexia of ageing group and 10.7% in the anorexia of ageing group (P < 0.001). Adjusted for covariates (except for frailty status), the participants with anorexia of ageing had an independently associated higher risk of incident disability compared with those without anorexia of ageing (hazard ratio: 1.43, 95% confidence interval: 1.04-1.95, P = 0.03). However, adjusted for covariates (including frailty status), anorexia of ageing was not significantly associated with incident disability (P = 0.09). Structural equation models revealed that anorexia of ageing had no direct effect on disability; however, anorexia of ageing was associated with frailty. CONCLUSIONS: Older adults with anorexia of ageing had a higher proportion of frailty and a higher prevalence proportion of disability compared with those without anorexia of ageing. Although anorexia of ageing may not have a direct effect on incident disability, the structural equation model suggests an indirect relationship between anorexia of ageing and incident disability via frailty status.

Herbal Medicine Ninjin'yoeito in the Treatment of Sarcopenia and Frailty.

Frailty and sarcopenia have recently gained considerable attention in terms of preventive care in Japan, which has an ever-increasing aging population. Sarcopenia is defined as atrophy of skeletal muscles caused by the age-related decrease in growth hormone/insulin-like growth factor and sex hormones. The Japanese Ministry of Health, Labor and Welfare reports that frailty can lead to impairment of both mental and physical functioning. Chronic diseases such as diabetes and dementia may underlie frailty. It is important to prevent progression of frailty and extend the healthy lifespan. In herbal medicine practice, including Japanese Kampo medicine, "Mibyo," a presymptomatic state, has long been recognized and may be applicable to frailty. Kampo medicines may include several medicinal plants and are thought to have the potential to improve symptoms of frailty, such as loss of appetite and body weight, fatigue, and sarcopenia, as well as anxiety, depression, and cognitive decline. Ninjin'yoeito (Ren Shen Yang Ying Tang) is the most powerful Kampo medicine and has been widely applied to palliative care of cancer patients. This review includes recent anti-aging studies and describes the effects and mechanisms of Ninjin'yoeito (Ren Shen Yang Ying Tang) when used for frailty or to extend a healthy life expectancy.

The association between anorexia of aging and physical frailty: Results from the national center for geriatrics and gerontology's study of geriatric syndromes.

OBJECTIVES: The present study examined the association between anorexia of aging and physical frailty among older people. STUDY DESIGN: An observational, cross-sectional cohort design was used with a sample of 4417 elderly Japanese citizens living in a community setting. MAIN OUTCOME MEASURES: Frailty was operationalized as the following frailty components: slowness, weakness, exhaustion, low level of physical activity, and weight loss. Participants were grouped as non-frail, pre-frail, and frail, and categorized as anorexic or not using questionnaire cutoff scores. Measured covariates were as follows: sociodemographic variables, medical history, life style, body mass index, blood nutrition data, self-rated health, depressive symptoms, and cognitive function. RESULTS: The prevalence of anorexia of aging in each group was as follows: non-frail, 7.9%; pre-frail, 14.8%; frail, 21.2% (P for trend<0.001). After adjusting for all covariates, independent associations were identified between anorexia of aging and slowness (OR 1.42, 95% CI: 1.14-1.75, P=0.002), exhaustion (OR 1.39, 95% CI: 1.11-1.74, P=0.004) and weight loss (OR 1.37, 95% CI: 1.05-1.79, P=0.019), but not weakness or low level of physical activity. CONCLUSIONS: Anorexia of aging is importantly associated with frailty and the following frailty components: slowness, exhaustion, and weight loss. Future research should prospectively examine frailty's causal connection with anorexia of aging.