SATOSHI KUROSE

Abstract Background Pre-cancer onset of cachexia raises uncertainties regarding the optimal timing for early intervention in lung cancer patients. We aimed to examine changes in physical function, nutritional status, and cachexia incidence in patients with lung cancer from the initial visit to treatment initiation and determine the effect of these changes on lung cancer treatment. Methods This single-center retrospective cohort study enrolled patients suspected of having advanced lung cancer who visited Kansai Medical University Hospital between January and February 2023 and were definitely diagnosed with the disease. Patients were categorized into three groups based on their cachexia status: those with cachexia at initial diagnosis (group C), those who developed cachexia between the initial visit and treatment initiation (group OC), and those without cachexia (group NC). Results Out of 61 patients, 21 had cachexia at their first outpatient visit (group C). The time between the first visit and treatment initiation was 42.5 days. The rate of cachexia in patients with stage IV lung cancer in group OC was significantly higher than that in patients with other stages (P = 0.008). Of the 33 patients with advanced lung cancer, 11 received supportive care only. The first-line treatment induction rate for the OC group was low. Half of the patients declined chemotherapy and received the best supportive care; their disease control rate (37.5%) was significantly worse than that of the other groups (P = 0.007). Conclusions Cachexia negatively impacts the effectiveness of initial cancer treatment, necessitating early anti-cachexia interventions at the first clinical visit.

OBJECTIVE: Follistatin (FST)/myostatin (MST) myokine-signaling axis is important for muscle metabolism and pathogenesis of obesity. FST, mainly secreted by skeletal muscle and liver, inhibits MST and affects skeletal muscle synthesis. This study aimed to identify the characteristics of myokines and independent predictors of serum FST levels in patients with obesity. METHODS: In this retrospective cross-sectional study, 226 patients (mean age, 46.6 years; men, 35.4%) with obesity who initially visited an outpatient clinic between June 2014 and September 2020, were included and classified into obesity (25.0 ≤ body mass index (BMI) < 35.0 kg/m2) and severe obesity (BMI ≥35 kg/m2) groups based on the guidelines of the Japan Society for the Study of Obesity. Body composition was measured using bioelectrical impedance analysis and computed tomography. Muscle strength, exercise tolerance, metabolic parameters, and myokines were measured, including serum levels of FST, MST, irisin, and brain-derived neurotrophic factor. RESULTS: Serum FST levels were significantly higher in the severe obesity group than in the obesity group (median: 768.4 vs. 895.1 pg/mL, P = 0.020). However, the levels of other myokines showed no significant differences between the groups. In Model 1, which included factors that significantly correlated with FST levels, stepwise multivariate regression analysis revealed peak oxygen uptake (VO2) as an independent predictor of FST levels based on the significance of the univariate analysis. Additionally, Model 2 was analyzed by adding myokine level to Model 1, revealing that peak VO2, MST, and irisin levels were independent predictors of FST levels. CONCLUSION: Serum FST levels were higher in patients in the severe obesity group compared to those in the obesity group. There was an independent association between low exercise tolerance and elevated serum FST levels.

PURPOSE: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy. METHODS: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery. RESULTS: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis. CONCLUSION: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy.

BACKGROUND: A limited number of studies have evaluated the masticatory indices of individuals with obesity who only chew their food a few times and for shorter duration or who were provided with an instructional intervention. This study aimed to examine the effects of a 6-month instructional mastication intervention on the body composition and biochemical indices in female patients with obesity. METHODS: Female patients with obesity were randomly classified into a conventional treatment group (CTG; 12 individuals), which only received normal nutritional and exercise guidance, and a mastication intervention group (MIG; 16 individuals), which received an additional mastication guidance. The MIG received guidance on foods requiring increased number of chews and chewing duration, eating techniques, and the proper method of cutting foods. RESULTS: Changes in the masticatory, body composition, and biochemical indices were compared before and after the 6-month intervention. The values of body composition indices decreased significantly in both groups; however, the rate of change in body mass index significantly decreased in the MIG. In addition, the values of biochemical indices were significantly decreased in the MIG compared with that in the CTG, which is attributed to the addition of mastication instruction to female patients with obesity. CONCLUSION: Increasing the number of chews and duration of chewing times for carbohydrates, which are staple foods, possibly contributed to weight loss and improvement of glucose metabolism. TRIAL REGISTRATION: UMIN, UMIN000025875. Registered on 27 Jan 2017.

BACKGROUND: This study investigated the effects of mobility restrictions (MRs) during the COVID-19 epidemic on physical activity, body composition, and exercise tolerance in patients with obesity. METHODS: We analyzed data of obesity patients participating in a 6-month weight loss program in February 2020, and after, when the epidemic was considered to have had some effect on outdoor activity in Osaka, Japan (MR group). MR group patients were compared to patients with obesity attending the program in 2018 and 2019 (non-MR group) who had a similar number of months as MR group. Changes in physical activity, body composition, and exercise tolerance (O2 consumption; VO2) owing to the weight loss program were analyzed between both groups using analysis of covariance and logistic regression analysis. RESULTS: Decreases in body fat were significantly higher in MR group than in non-MR group. However, increases in physical activity, VO2 at anaerobic threshold, and peak VO2 were significantly lower in MR group; however, increases in peak VO2 owing to the weight loss program were less likely to be achieved in MR group (odds ratio, 0.21; 95% confidence interval, 0.06-0.81). CONCLUSION: MR during the COVID-19 epidemic may have affected the exercise tolerance of patients with obesity.

BACKGROUND: Adiponectin has been reported to be associated with lower skeletal muscle mass and skeletal strength and may be involved in skeletal muscle regulation along with myostatin. This study aims to evaluate the association between serum adiponectin and myostatin levels and identify independent factors using body composition and metabolic parameters in patients with obesity. METHODS: Overall, 148 patients (age, 45.9 ± 14.3 years, body mass index, 37.2 ± 8.0 kg/m2) who initially visited the outpatient clinic of obesity between November 2013 and November 2019 were included. Body composition was measured using InBody 720 and dual energy X-ray absorptiometry. In addition, muscle strength, vascular function, and metabolic parameters were measured. Serum levels of adiponectin, leptin, myostatin, and irisin were measured from blood samples. RESULTS: The serum adiponectin level was 2.9 μg/mL (1.7-4.1 μg/mL), and the serum myostatin level was 2398.4 pg/mL (1,777.1-2952.5 pg/mL). The stepwise regression analysis revealed less leg strength, homeostasis model assessment of insulin resistance, and C-reactive protein as an independent predictor of serum adiponectin levels based on the significance of the univariate analysis (R2 = 0.190, P < 0.001). A high appendicular lean mass/body weight, reactive hyperemia index, and irisin were independent factors for serum myostatin levels (R2 = 0.260, P < 0.001). CONCLUSION: The serum adiponectin level was associated with less muscle strength. Although serum myostatin was associated with a high appendicular lean mass, it is possible that myostatin was regulated by the percentage of body weight from appendicular lean mass.

Objective: DNA methylation is an epigenetic mechanism that regulates gene expression. The obesity-related (FTO) gene is the first gene found to be associated with fat mass and obesity. However, no studies have examined the relationship between weight-loss intervention effect and FTO methylation in obese individuals with whole blood DNA. The purpose of this study was to quantify FTO whole blood DNA methylation and investigate the relationship between body composition, exercise capacity, and blood parameters with a 6-month weight-loss program intervention. Participants and Methods: Eighteen female participants (mean age, 50.6 ±12.1 years, body mass index (BMI), 33.5 ± 6.2 kg/m2) who completed a 6-month weight-loss program at the obesity outpatient department at the Health Science Center of Kansai Medical University Hospital from March 2017 to October 2018 were included in the analysis. Participants were randomized into a normal treatment group (NTG) and a group with additional resistance training (RTG). Body composition, exercise tolerance and metabolic index were measured in each participant. DNA methylation status in whole blood samples was determined using pyrosequencing. All measurements were taken during the first visit and at the 6-month post-intervention visit. Results: The methylation rate was significantly decreased in the NTG in CpG1 (p=0.011) and total value of CpG (p=0.011), whereas in the treatment group containing resistance training (RTG), CpG3 (p=0.038) was increased significantly. Furthermore, the independent factors that determine %CpG3 of RTG were visceral fat area change rate (%VFA) (β = -0.568, P = 0.007, R2 = 0.527) and resistance training (β = 0.517, P = 0.012, R2 = 0.527), which have been extracted. Conclusion: A 6-month weight-loss program, including resistance training, may be associated with decreased visceral fat area changes and increased RTG CpG3 methylation changes. However, further replication studies with larger sample sizes are warranted to verify the findings of this study.

BACKGROUND: Although exercise is a standard treatment for postoperative osteoarthritis, interindividual differences have been reported. Epigenetic modification (DNA methylation), a factor causing interindividual differences, is altered by the environment and may affect all tissues. Performing a tissue biopsy to investigate methylation of skeletal muscle fat metabolism genes is invasive, and less invasive and convenient alternatives such as blood testing are desired. However, the relationship between tissue and blood is still unclear. Here, we examined the relationship between DNA methylation of the PDK4 gene in skeletal muscle and peripheral blood. PATIENTS AND METHODS: Five patients who underwent artificial knee arthroplasty between April 2017 and June 2018 at Kansai Medical University Hospital were included (2 men and 3 women; average age, 75.2 years; body mass index, 26.1 kg/m2). We measured the body composition of the patients using dual-energy X-ray absorptiometry. Peripheral blood was collected at the time of hospitalization and 5 months after surgery; skeletal muscles were collected at the time of surgery and 5 months after surgery. Rehabilitation was performed according to the clinical procedure for 3 months after surgery. Patients performed resistance training and aerobic exercise using an ergometer for 20 min twice a week. Biopsy samples were treated with bisulfite after DNA extraction, and the methylation rate was calculated at different CpG islands downstream from the transcription initiation codon of the PDK4 gene. RESULTS: No significant change in body composition was observed before and after postoperative exercise therapy, and no significant change was noted in the methylation at each position in the promoter region of PDK4 in the skeletal muscle and peripheral blood. However, changes in the methylation rate at CpG1 in peripheral blood significantly correlated with those in skeletal muscle (P = 0.037). Furthermore, the amount of change in the methylation rate of CpG1 in the skeletal muscle was significantly correlated (P = 0.037) with the average methylation rate at the promoter region in peripheral blood. CONCLUSIONS: Methylation rates at CpG1 in the skeletal muscle and peripheral blood were significantly correlated, suggesting that skeletal muscle methylation could be analyzed via peripheral blood rather than skeletal muscle biopsy.

BACKGROUND: Toe grip-related training requires individuals to actively exercise muscles that are not frequently used; therefore, it may improve not only toe grip strength but also cognitive function. The purpose of this study was to examine the effects of toe grip-related training on predictors of physical performance and cognitive function in nursing home residents. METHODS: A total of 35 nursing home residents (35 left and 35 right feet; mean age, 82.1 ± 7.9 years) were included in this study. The participants were divided into two groups: a training group and a control group. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function of the participants, and the Fall Risk Index (FRI) was used to evaluate the risk of falls. Toe grip-related physical function was also assessed. Baseline endpoints were evaluated and the effects of toe grip-related training were examined following a 12-week training intervention. RESULTS: The training group showed significant improvements in MMSE score, FRI score, toe grip strength, and the toe skill (TS) test; however, the control group did not show these changes. The training group showed significant increases in Δ MMSE, Δ toe grip strength, and Δ TS (right foot) than the control group. Stepwise regression analysis revealed that Δ toe grip strength is an independent factor of Δ MMSE. CONCLUSIONS: Toe grip training improves not only toe grip strength itself, but also cognitive function. Furthermore, change in toe grip strength was an independent factor of change in MMSE in those populations. TRIAL REGISTRATION: UMIN, UMIN000027437 . Registered on 26 May 2017.

Purpose: DNA methylation is thought to play a role in exercise-induced gene expression. We aimed to examine changes in muscular strength and body composition in elderly patients with end-stage knee osteoarthritis before and after artificial knee arthroplasty and exercise therapy. We aimed to confirm the relationship between DNA methylation and body composition, using the methylation rate of the pyruvate dehydrogenase kinase 4 (PDK4) gene that regulates skeletal muscle and fat metabolism. Patients and methods: Patients underwent artificial knee arthroplasty between April 2017 and June 2017 at Kansai Medical University Hospital. Six patients (seven knees) were included in the analysis (four males/two females; average age, 75.7 years; body mass index, 25.1 kg/m2). Body composition and knee extension muscle strength were measured before surgery and 5 months after surgery. Rehabilitation was performed for 3 months after surgery. In the remaining 2 months, patients performed resistance training and aerobic exercise using an ergometer for 20 mins, twice a week. A biopsy of the vastus medialis was taken during surgery and 5 months post-surgery. Biopsy samples were treated with bisulfite after DNA extraction, and DNA methylation rate was calculated. Results: Body weight (P=0.046), total weight (P=0.027), and total fat mass (P=0.028) were significantly lower 5 months postoperatively than preoperatively. Five months post-surgery, the PDK4 gene was significantly more hypomethylated at eight sites in the CpG island, compared to pre-surgery. There was a significant correlation (r=0.88, P=0.02) between promoter region hypomethylation and weight loss. Total methylation rate and weight loss were significantly correlated (r=0.829, P=0.042). Total methylation rate and decrease in total fat mass showed a positive trending relationship (r=0.812, P=0.05). Conclusion: Rehabilitative exercise resulted in significant decreases in weight and body fat. Hypomethylation of the PDK4 gene promoter region signified the effect of postoperative management focus on exercise therapy on weight and fat loss.

BACKGROUND: Because of the advanced age of patients with cardiovascular disease (CVD), prevention of sleep disorder and dementia is a priority for cardiac rehabilitation (CR) during their long-term care. This study aimed to investigate the association of physical activity with sleep quality and cognitive function in elderly patients with CVD in the CR maintenance phase. METHODS: We conducted a multicenter study through the Clinical Exercise Physiology Association Japan network, which included 102 elderly patients (mean age, 74±7.4 years) with CVD undergoing phase III CR at 6 institutions. Physical activity was assessed using a triaxial accelerometer for 7 consecutive days and was classified as locomotive and household activities. Physical fitness was assessed via 6-min walking distance (6MD), hand grip power, 10-m walking speed, one leg standing time with eyes open, and 10 times sit-to-stand tests. Sleep quality and cognitive function were evaluated using the Pittsburgh sleep quality index (PSQI) and mini-mental state examination (MMSE) scores, respectively. RESULTS: The patients performed 5506.8±3743.6 steps/day and scored 5.8±3.5 points in the PSQI and 28.4±1.7 points in the MMSE. Sleep latency and MMSE scores correlated with locomotive activity, but not with household activity. Locomotive activity and 6MD were independent predictors of sleep latency and MMSE score, respectively. When patients with heart failure were excluded, the relationship between sleep latency and locomotive activity was preserved, but the relationship between exercise tolerance and cognitive function disappeared. CONCLUSION: Locomotive activity and exercise tolerance are associated with sleep latency and cognitive function in elderly patients with CVD continuing phase III CR. However, in this study, the relationship between exercise tolerance and cognitive function was offset by the presence of heart failure.

BACKGROUND: Toe grip strength is the force of a toe on a surface. The objective of this study was to investigate the relationship between falls in middle-aged individuals and physical strength factors such as toe grip strength and knee extension strength. METHODS: The subjects were 194 middle-aged individuals (388 feet) who were independent in daily life, received no nursing care, and participated in a health sports event organized by a sports club. We evaluated the body composition, blood pressure, vascular age, systemic response, bone density, knee extension strength, and toe grip strength, and examined their relationship using a self-administered questionnaire survey. RESULTS: The fall, near-fall, and no fall groups included 7, 36, and 151 subjects, respectively; the high and low risk groups included 43 and 151 subjects, respectively. Logistic regression analysis was performed with risk of falls as the dependent variable, and factors that showed a significant difference in the comparison of the high and low risk groups as independent variables. In this analysis, toe grip strength and diastolic blood pressure were identified as independent risk factors for a fall. CONCLUSIONS: Toe grip strength is an independent risk factor for falls, and improvement of toe grip strength might prevent falls.