Effect of the Gastrojejunostomy Position on the Postoperative Amount of Oral Intake in Pancreaticoduodenectomy.

INTRODUCTION: We investigated the effect of the gastrojejunostomy position on the postoperative oral intake in patients who have undergone pancreaticoduodenectomy (PD). METHODS: We investigated 119 patients who underwent PD between June 2013 and December 2019 and examined the effect of the horizontal and vertical distance rates of the gastrojejunostomy position on the postoperative oral intake. The patients were categorized as having poor or good oral intake based on whether their intake was up to half the required calorie intake. RESULTS: There were significant differences in the number of cases with grade B or C postoperative pancreatic fistula (good, 20.3% vs. poor, 60.0%; p < 0.001), horizontal distance rate (good, 0.57 vs. poor, 0.48; p = 0.02), and postoperative hospitalization period (good, 15 vs. poor, 35 days; p < 0.001). However, there was no significant difference in the vertical distance rate (good, 0.67 vs. poor, 0.71; p = 0.22). The horizontal distance rate was the independent risk factor for postoperative poor oral intake at 2-3 weeks (risk ratio, 3.69; 95% CI: 1.48-9.20). DISCUSSION: The oral intake was greater in patients whose gastrojejunostomy position in PD was farther from the median, suggesting the necessity of intraoperative placement of the gastrojejunostomy position as far from the median as possible.

Factors Affecting Energy Metabolism and Prognosis in Patients with Amyotrophic Lateral Sclerosis.

BACKGROUND/AIMS: Nutritional status is a factor affecting prognosis in patients with amyotrophic lateral sclerosis (ALS). Here, we aimed to clarify the factors associated with hypermetabolism and the prognosticators of ALS. METHODS: Forty-two inpatients (22 men, 20 women) diagnosed with ALS according to the revised El-Escorial criteria were investigated. The following data were retrospectively analyzed: anthropometric measurements, blood biochemistry, disease severity, basal energy expenditure (BEE), resting energy expenditure (REE) measured by indirect calorimetry, spirometry, and bioelectrical impedance analysis. Single and multiple regression analysis was performed to examine factors affecting REE and metabolic changes (defined as the ratio of REE to fat-free mass [FFM]). The Kaplan-Meier method was used to examine factors associated with the occurrence of cumulative events (death or tracheostomy). RESULTS: Among the 42 inpatients, REE was significantly higher than BEE, indicating hypermetabolism in ALS. Multiple regression analysis revealed that REE/FFM is strongly associated with the skeletal muscle index (-3.746 to -1.532, p < 0.0001) and percent forced vital capacity (%FVC) (-0.172 to -0.021, p = 0.013). Moreover, both the skeletal muscle index and %FVC were significant prognosticators associated with the occurrence of cumulative events. CONCLUSIONS: Energy metabolism was elevated in ALS, and respiratory status and muscle mass were associated with the hypermetabolism and poor prognosis. Adequate nutritional support may improve outcomes in ALS by preventing deterioration of respiratory status and reduction in muscle mass.

Energy Metabolism and Nutritional Status in Hospitalized Patients with Chronic Heart Failure.

INTRODUCTION: Malnutrition is a factor that defines vital prognosis in chronic heart failure. OBJECTIVE: This study investigated nutritional and metabolic disorders in patients with heart failure by examining the association of severity of heart failure with inflammatory cytokines, appetite-regulating hormones, and energy metabolism. METHODS: Subjects were 50 patients with heart failure. On admission, nutritional status was assessed, and biochemical blood tests were performed, including for serum tumor necrosis factor-α, interleukin-6, ghrelin, and leptin levels. Resting energy expenditure (REE) was also measured by indirect calorimetry to examine its association with severity of heart failure and levels of inflammatory cytokines and appetite-regulating hormones. RESULTS: There were significant associations between serum brain natriuretic peptide (BNP) level and nutrition indices, indicating that nutritional status was worse when heart failure was more severe. Inflammatory cytokine levels showed significant positive correlations with BNP level. Measured REE/bodyweight was not associated with severity of heart failure, but was negatively correlated with body fat percentage and leptin levels. CONCLUSIONS: Energy metabolism was not associated with serum BNP level among patients with heart failure with New York Heart Association functional class up to III. Body fat percentage and leptin levels may be a good predictor of energy metabolism in patients with heart failure.

Validity of the Use of a Triaxial Accelerometer and a Physical Activity Questionnaire for Estimating Total Energy Expenditure and Physical Activity Level among Elderly Patients with Type 2 Diabetes Mellitus: CLEVER-DM Study.

INTRODUCTION: Evaluation of total energy expenditure (TEE) and physical activity level (PAL) is important for treatment of patients with type 2 diabetes mellitus (T2DM). However, the validity of accelerometers (ACC) and physical activity questionnaires (PAQ) for estimating TEE and PAL remains unknown in elderly populations with T2DM. We evaluated the accuracy of TEE and PAL results estimated by an ACC (TEEACC and PALACC) and a PAQ (TEEPAQ and PALPAQ) in elderly patients with T2DM. METHODS: Fifty-one elderly patients with T2DM (aged 61-79 years) participated in this study. TEEACC was calculated with PALACC using a triaxial ACC (Active style Pro HJA-750c) over 2 weeks and predicted basal metabolic rate (BMR) by Ganpule's equation. TEEPAQ was estimated using predicted BMR and the PALPAQ from the -Japan Public Health Center Study-Long questionnaire. We compared the results to TEEDLW measured with the doubly labeled water (DLW) method and PALDLW calculated with BMR using indirect calorimetry. RESULTS: TEEDLW was 2,165 ± 365 kcal/day, and TEEACC was 2,014 ± 339 kcal/day; TEEACC was strongly correlated with TEEDLW (r = 0.87, p < 0.01) but significantly underestimated (-150 ± 183 kcal/day, p < 0.05). There was no significant difference in TEEPAQ and TEEDLW (-49 ± 284 kcal/day), while the range of difference seemed to be larger than TEEACC. PALDLW, PALACC, and PALPAQ were calculated to be 1.71 ± 0.17, 1.69 ± 0.16, and 1.78 ± 0.24, respectively. -PALACC was strongly correlated with PALDLW (r = 0.71, p < 0.01), and there was no significant difference between the 2 values. PALPAQ was moderately correlated with PALDLW (r = 0.43, p < 0.01) but significantly overestimated. Predicted BMR was significantly lower than the BMR -measured by indirect calorimetry (1,193 ± 186 vs. 1,262 ± 155 kcal/day, p < 0.01). CONCLUSIONS: The present ACC and questionnaire showed acceptable correlation of TEE and PAL compared with DLW method in elderly patients with T2DM. Systematic errors in estimating TEE may be improved by the better equation for predicting BMR.

The effect of preoperative synbiotic treatment to prevent surgical-site infection in hepatic resection.

We aimed to clarify the influence of preoperative synbiotic therapy on surgical-site infections (SSIs) after hepatic resection. Between January 2011 and December 2017, 284 patients who underwent hepatic resection without biliary tract reconstruction and resection of other organs were included. We prospectively administered Clostridium butyricum and partially hydrolyzed guar gum before hepatic resection between April 2016 and December 2017 (synbiotic group). One-hundred-fifteen patients of the synbiotic group and 169 patients (conventional group) treated between January 2011 and the end of March 2016 were compared using propensity score matching. The frequency of laparoscopic resection was significantly larger in the synbiotic group (conventional group; 28% vs synbiotic group; 55%, p<0.001) and the amount of intraoperative bleeding was significantly smaller in the synbiotic group (median; conventional group, 700 ml vs synbiotic group, 200 ml; p<0.001). The postoperative SSI was significantly lower in the synbiotic group of six patients (5.2%) than in the conventional group of 30 patients (17.8%) (p = 0.002). Sixty patients in each group remained after propensity score matching. There was no significant difference in the incidence of SSI between the groups (conventional group, 15% vs synbiotic group, 6.7%; p = 0.239). In conclusion, preoperative synbiotic treatment did not reduce SSIs after hepatic resection.

Low Body Mass Index and Myeloablative Conditioning Regimen Prolong the Duration of Parenteral Nutrition During Hematopoietic Stem Cell Transplantation.

BACKGROUND/AIMS: Patients undergoing hematopoietic stem cell transplantation (HSCT) often receive total parenteral nutrition (TPN) due to poor oral intake. In clinical practice, it is difficult to predict adequate nutritional management, especially the duration of parenteral nutrition (PN), because of inter-individual variability in the conditions and types of treatment regimens. This study investigated the relationship between patient factors and the duration of TPN and the duration of PN. METHODS: Data on clinical features, patient characteristics, and the duration of TPN and PN were collected from medical records of 61 of 73 patients who underwent HSCT between April 2010 and December 2014 and were analyzed by multiple linear regression analysis. RESULTS: Forty-nine patients (80.3%) received TPN and 53 (86.9%) received PN. Sixty patients were affected by poor oral intake soon after pretreatment. Body mass index (BMI) was significantly correlated with the duration of TPN (ß = -2.733; 95% CI -4.679 to -0.787). BMI (ß = -2.260; 95% CI -4.304 to -0.213) and conditioning regimen (ß = 12.726; 95% CI 0.692-24.76) were significantly correlated with the duration of PN. CONCLUSIONS: BMI at admission and the type of conditioning regimen should be considered in choosing the nutritional management plan in patients with HSCT with poor oral intake.

Nutritional Screening and Clinical Outcome in Hospitalized Patients with Crohn's Disease.

BACKGROUND/AIMS: Hospitalized patients with Crohn's disease (CD) can develop severe nutritional deficits. However, the nutritional screening tools with the most utility for such patients are still unknown. METHODS: Nutritional status of 40 CD patients was assessed on admission using several screening tools and laboratory tests. Their validity was evaluated in relation to length of hospital stay (LOS) and intestinal resection. Receiver operating characteristic analysis was performed to predict prolonged LOS (≥28 days). RESULTS: Prolonged LOS was correlated with each of the following screening parameters: Subjective Global Assessment, Nutrition Risk Screening 2002 (NRS 2002), Onodera's Prognostic Nutritional Index (O-PNI), Controlling Nutritional Status, serum albumin level, and weight loss. These parameters were not correlated with intestinal resection. Evaluation of prognostic yield showed cutoff values of serum albumin 3.3 g/dL (AUC 0.797, sensitivity 57.1%, specificity 89.5%) and O-PNI 36.5 (0.749, 71.4%, 73.7%). By combining the serum albumin cutoff value and NRS 2002 score, patients were divided into 4 groups, with a prolonged LOS rate of 68.2% in the group with the worst prognosis. CONCLUSIONS: A combination of serum albumin (given the simplicity of testing) and NRS 2002 as nutritional screening tools may be useful for hospitalized CD patients.

Energy metabolism and nutritional status in hospitalized patients with lung cancer.

This study aimed to investigate the energy metabolism of patients with lung cancer and the relationship between energy metabolism and proinflammatory cytokines. Twenty-eight patients with lung cancer and 18 healthy controls were enrolled in this study. The nutritional status upon admission was analyzed using nutritional screening tools and laboratory tests. The resting energy expenditure and respiratory quotient were measured using indirect calorimetry, and the predicted resting energy expenditure was calculated using the Harris-Benedict equation. Energy expenditure was increased in patients with advanced stage disease, and there were positive correlations between measured resting energy expenditure/body weight and interleukin-6 levels and between measured resting energy expenditure/predicted resting energy expenditure and interleukin-6 levels. There were significant relationships between body mass index and plasma leptin or acylated ghrelin levels. However, the level of appetite controlling hormones did not affect dietary intake. There was a negative correlation between plasma interleukin-6 levels and dietary intake, suggesting that interleukin-6 plays a role in reducing dietary intake. These results indicate that energy expenditure changes significantly with lung cancer stage and that plasma interleukin-6 levels affect energy metabolism and dietary intake. Thus, nutritional management that considers the changes in energy metabolism is important in patients with lung cancer.

Comparison of energy metabolism and nutritional status of hospitalized patients with Crohn's disease and those with ulcerative colitis.

This study aimed to compare the nutritional status and energy expenditure of hospitalized patients with Crohn's disease (CD) and those with ulcerative colitis (UC). Twenty-two hospitalized patients with CD and 18 patients with UC were enrolled in this study. We analyzed nutritional status upon admission by using nutritional screening tools including subjective global assessment, malnutrition universal screening tool, and laboratory tests. We measured resting energy expenditure (mREE) of the patients with indirect calorimetry and predicted resting energy expenditure (pREE) was calculated by using the Harris-Benedict equation. Results presented here indicate no significant difference in nutritional parameters and energy metabolism between CD and UC patients. In UC patients, a significant correlation was observed between mREE/body weight and disease activity detected by the Lichtiger and Seo indices. However, there was no correlation between mREE/body weight and Crohn's disease activity index in CD patients. Inflammatory cytokine interleukin-6 levels correlated with mREE/pREE in CD and UC patients while tumor necrosis factor-α was not. In conclusion, energy expenditure significantly correlated with disease activity in UC patients but not in CD patients. These results indicate that establishing daily energy requirements based on disease activity of UC is imperative for improving the nutritional status of patients.

Changes in energy metabolism after induction therapy in patients with severe or moderate ulcerative colitis.

We investigated the changes in energy expenditure during induction therapy in patients with severe or moderate ulcerative colitis. Thirteen patients (10 men, 3 women; mean age, 36.5 years) with ulcerative colitis admitted to the Shiga University Hospital were enrolled in this study. We measured the resting energy expenditure and respiratory quotients of these patients before and after induction therapy with indirect calorimetry. We analyzed the changes of nutritional status and serum inflammatory cytokine levels and also evaluated the relationship between energy metabolism and disease activity by using the Seo index and Lichtiger index. The resting energy expenditure was 26.3 ± 3.8 kcal/kg/day in the active stage and significantly decreased to 23.5 ± 2.4 kcal/kg/day after induction therapy (p<0.01). The resting energy expenditure changed in parallel with the disease activity index and C-reactive protein and inflammatory cytokine levels. The respiratory quotient significantly increased after induction therapy. Thus, moderate to severe ulcerative colitis patients had a hyper-metabolic status, and the energy metabolism of these patients significantly changed after induction therapy. Therefore, we recommend that nutritional management with 30-34 kcal/kg/day (calculated as measured resting energy expenditure × activity factor, 1.3) may be optimal for hospitalized ulcerative colitis patients.

Changes of energy metabolism, nutritional status and serum cytokine levels in patients with Crohn's disease after anti-tumor necrosis factor-α therapy.

We investigated the effects of treatment with antibodies against tumor necrosis factor (TNF)-α on energy metabolism, nutritional status, serum cytokine levels in patients with Crohn's disease (CD). Twelve patients were enrolled. Resting energy expenditure (REE) levels were measured by indirect calorimetry. Crohn's disease activity index (CDAI) significantly decreased after treatment with anti-TNF-α therapy. Anti-TNF-α therapy did not affect REE, but respiratory quotient (RQ) significantly increased after treatment. Serum interleukin-6 levels were significantly decreased and RQ were significantly increased in high REE (≥25 kcal/kg/day) group as compared to low REE (<25 kcal/kg/day) group. In conclusion, high REE value on admission is a predictive factor for good response to treatment with anti-TNF-α antibodies in active CD patients.

Ideal body weight-based determination of minimum oral calories beneficial to function and survival in ALS.

Introduction: This study sought to identify the optimal caloric intake to improve function and survival in ALS patients by comparing oral intake per ideal body weight (IBW) and its discrepancy with total energy expenditure (TEE) using the Shimizu formula. Methods: A retrospective analysis of 104 ALS patients was conducted, categorizing them based on their average intake during the first week after admission using two primary intake cutoffs: 25 kcal/kgIBW and 30 kcal/kgIBW. The variance between oral intake and TEE was also evaluated using -300 kcal and 0 kcal as reference points. Results: Oral caloric intake per IBW and functional decline rate (rs = -0.35, p < 0.001), but the variance from TEE was not significantly correlated (-0.11, p = 0.27). Survival data showed that patients consuming less than 25 kcal/kgIBW had a median survival of 24 months, increasing to 38 months for those consuming between 25-30 kcal/kgIBW and 63 months for those consuming 30 kcal/kgIBW or more. Deviations from the TEE did not significantly affect survival (p = 0.36). Among patients consuming less than their TEE, those consuming less than 25 kcal/kgIBW had a shorter median survival (24 months) compared to their counterparts (46 months) (p = 0.022). Consumption of less than 25 kcal/kgBW emerged as a significant negative predictor of patient outcome, independent of factors such as age, gender or disease progression. Discussion: Intakes of 25 kcal/kgIBW or more are correlated with improved ALS outcomes, and larger, multi-regional studies are recommended for deeper insights.

Investigation of the prognostic predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex and hypermetabolism.

The prognostic predictive value of lipid profiling in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we aimed to clarify the value of the levels of serum lipids, including high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), for predicting the prognosis in ALS. This was a single-center retrospective study of 78 patients with ALS. The serum lipid profiles at the first hospital visit after symptom onset were analyzed to determine the correlations of lipids with survival and physical parameters, including nutritional, respiratory, and metabolic conditions. The cutoff level for high HDL was defined as the third quartile, while that of low LDL and TG, as the first quartile. Hypermetabolism was defined as the ratio of resting energy expenditure to lean soft tissue mass ≥ 38 kcal/kg. High HDL was an independent factor for poor prognosis in all patients (hazards ratio [HR]: 9.87, p < 0.001) in the Cox proportional hazard model, including %vital capacity and the monthly decline rate in body mass index and the Revised Amyotrophic Lateral Functional Rating Scale score from symptom onset to diagnosis. Low LDL was a factor for poor prognosis (HR: 6.59, p = 0.017) only in women. Moreover, subgroup analyses with log-rank tests revealed that the prognostic predictive value of high HDL was evident only in the presence of hypermetabolism (p = 0.005). High HDL predicts poor prognosis in all patients, whereas low LDL, only in women. Hypermetabolism and high HDL synergistically augment the negative effect on prognosis.

Prognostic prediction by hypermetabolism varies depending on the nutritional status in early amyotrophic lateral sclerosis.

To examine whether hypermetabolism could predict the prognosis of early amyotrophic lateral sclerosis (ALS) patients with differing nutritional profiles. This single-center, retrospective study examined the prognosis of ALS patients with hypermetabolism in relation to their nutritional status at hospitalization. The metabolic state was estimated by the ratio of measured resting energy expenditure (mREE) to lean soft tissue mass (LSTM) (mREE/LSTM), wherein patients with ratios ≥ 38 were defined as hypermetabolic. Malnutrition was defined as %ideal body weight < 0.9. Forty-eight patients were enrolled in this study. The hypermetabolic group had shorter survival in the normal-weight group but more prolonged survival in the malnutrition group. Multiplication of nutritional and metabolic factors, such as [(body mass index (BMI) - 19.8) × (mREE/LSTM - 38)], designated as BMI-muscle metabolism index (BMM index), successfully predicted the prognosis in the group with a high BMM index (≥ 1), which showed shorter survival and a faster rate of weight loss and functional decline. Multivariate analysis using the Cox model showed high BMM index was an independent poor prognostic factor (hazard ratio: 4.05; p = 0.025). Prognostic prediction by hypermetabolism varies depending on the nutritional status in ALS, and the BMM index is a consistent prognostic factor.

Assessment of Body Composition From CT Images at the Level of the Third Lumbar Vertebra in Inflammatory Bowel Disease.

BACKGROUND: Although there are several reports of associations between body composition parameters and outcomes in patients with inflammatory bowel disease (IBD), it is not clear which muscle tissue parameters and/or adipose tissue parameters most strongly affect outcomes. Therefore, this study sought to determine the associations of such parameters determined at the level of the third lumbar vertebra (L3) on computed tomography (CT) images with outcomes in IBD patients. METHODS: Subjects were IBD patients who were admitted to our hospital and underwent abdominal CT. The following parameters were assessed: skeletal muscle index, psoas muscle index, visceral adipose tissue/height index, visceral to subcutaneous adipose tissue area ratio, and intramuscular adipose tissue content. In this study, short- and long-term outcomes were defined as prolonged length of stay (≥30 days) and intestinal resection during the overall period of observation, respectively. RESULTS: In total, 187 patients were enrolled, 99 with Crohn's disease and 88 with ulcerative colitis. For all IBD patients, multivariate logistic regression analysis revealed that low albumin level and low psoas muscle index on admission were associated with prolonged length of stay. Multivariate Cox regression analysis revealed that male sex, Crohn's disease (not ulcerative colitis), low psoas muscle index, and high visceral to subcutaneous adipose tissue area ratio were associated with intestinal resection. CONCLUSIONS: This study revealed that muscle volume is associated with the short-term outcome of prolonged length of stay, whereas muscle volume and visceral adipose tissue volume (relative to subcutaneous adipose tissue volume) are associated with the long-term outcome of intestinal resection.

Inflammatory cytokines, appetite-regulating hormones, and energy metabolism in patients with gastrointestinal cancer.

This study investigated energy metabolism and its association with inflammatory cytokines and appetite- regulating hormones in patients with gastrointestinal cancer. Subjects were inpatients scheduled to undergo therapeutic intervention for diagnosed gastrointestinal cancer. Nutritional status on admission was assessed based on anthropometric measurements, nutrition screening results, food intake rate (energy intake/energy provided in hospital food), and biochemical test results. Fat-free mass (FFM) was measured using the bioelectrical impedance analysis. Resting energy expenditure (REE) and respiratory quotient were measured with indirect calorimetry, and basal energy expenditure (BEE) was calculated using the Harris-Benedict equation. A total 51 patients with gastrointestinal cancer were enrolled (17 with esophageal cancer, 15 with gastric cancer, and 19 with colorectal cancer); 16 had stage I disease, 11 had stage II, 13 had stage III, and 11 had stage IV. The levels of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α increased significantly with cancer stage progression (P<0.001; Jonckheere-Terpstra trend test). The REE/body weight and the REE/FFM tended to increase with cancer stage progression (P=0.064 and P=0.053, respectively; Jonckheere-Terpstra trend test). FFM showed a significant negative correlation with the level of TNF-α (P=0.008; Spearman's correlation coefficient). Also, food intake rate showed a significant negative correlation with levels of IL-6 and TNF-α (P<0.001). The level of active ghrelin was positively correlated with that of IL-6 and energy metabolism (P=0.004 and 0.016, respectively) and negatively correlated with food intake rate (P=0.035), which suggests a state of ghrelin resistance. In conclusion, this study confirmed increases in the levels of inflammatory cytokines with the progression of gastrointestinal cancer and suggested the possible association of such increases with decreased FFM and the increased energy metabolism. However, the increased levels of active ghrelin failed to compensate for cachexia in cancer patients.

Impact of obesity on underreporting of energy intake in type 2 diabetic patients: Clinical Evaluation of Energy Requirements in Patients with Diabetes Mellitus (CLEVER-DM) study.

BACKGROUND & AIMS: Although accurate assessment of energy intake (EI) is critical in diabetes care, underreporting of EI on dietary records (DR) is often an issue. However, few studies have examined EI with doubly labeled water (DLW) in patients with diabetes mellitus. We aimed to investigate the impact of sex and obesity on the dissociation of DR from total energy expenditure (TEE) evaluated with DLW in patients with type 2 diabetes. METHODS: Fifty-two patients with type 2 diabetes aged 60-79 years were enrolled for the Clinical Evaluation of Energy Requirements in Patients with Diabetes Mellitus (CLEVER-DM) study at a single university hospital. TEE was measured over 14 days by the DLW method as standard. EI was calculated by assessment of 3-day DR by registered dietitians. RESULTS: The mean difference between EI and TEE was 238 ± 412 kcal/day (~10% of TEE). Neither EI nor TEE was significantly different between obese (body mass index (BMI) ≥25 kg/m2) and non-obese (BMI <25 kg/m2) patients. There was a negative correlation between EI/TEE ratio and BMI in women (R = -0.437, P = 0.033) but not in men (R = -0.174, P = 0.377). There was a significant difference in EI/TEE ratio between obese and non-obese patients among women (0.85 ± 0.15 vs. 1.01 ± 0.21, P = 0.045) but not men (0.85 ± 0.20 vs. 0.87 ± 0.17, P = 0.79). CONCLUSIONS: EI calculated by 3-day DR may underestimate habitual intake, which is assumed to be equal to TEE measured by the DLW method except in non-obese women with diabetes. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000023051.

Total energy expenditure is comparable between patients with and without diabetes mellitus: Clinical Evaluation of Energy Requirements in Patients with Diabetes Mellitus (CLEVER-DM) Study.

Objective: Assessment of total energy expenditure (TEE) is essential for appropriate recommendations regarding dietary intake and physical activity in patients with and without diabetes mellitus (DM). However, few reports have focused on TEE in patients with DM, particularly in Asian countries. Therefore, we evaluated TEE in Japanese patients with DM using the doubly labeled water (DLW) method and physical activity level (PAL). Research design and methods: In this cross-sectional observational study, we evaluated 52 patients with type 2 DM and 15 patients without DM. Free-living TEE was measured over 12-16 days by the DLW method, and PAL was calculated as TEE divided by the basal metabolic rate (BMR) as assessed by indirect calorimetry. The equivalence margin was defined as 5 kcal/kg/day. Results: The numbers of patients with DM treated with insulin, oral antidiabetic drugs, and diet were 18 (34.6%), 20 (38.5%), and 14 (26.9%), respectively. The mean±SD level of glycated hemoglobin was 6.9%±0.8% and 5.5%±0.3% in the DM and non-DM group, respectively (p<0.001). The mean body mass index was 23.3±3.0 and 22.7±2.1 kg/m2 in the DM and non-DM group, respectively. The mean TEE per kilogram body weight adjusted for sex and age was 36.5 kcal/kg/day and 37.5 kcal/kg/day in the DM and non-DM group, respectively, with no significant difference (mean difference, -1.0 kcal/kg/day; 95% CI -4.2 to 2.3 kcal/kg/day). The BMR tended to be higher in the DM than in the non-DM group (mean difference, 33 kcal/day; 95% CI, -15 to 80 kcal/day). The mean PAL adjusted for sex and age was 1.71 and 1.81 in the DM and non-DM group, respectively, without a significant difference (mean difference, -0.10; 95% CI -0.21 to 0.01). Conclusion: TEE was comparable between Japanese patients with and without DM. Trial registration number: UMIN000023051.

Serum concentrations of trace elements in patients with Crohn's disease receiving enteral nutrition.

We investigated the trace element status in Crohn's disease (CD) patients receiving enteral nutrition, and evaluated the effects of trace element-rich supplementation. Thirty-one patients with CD were enrolled in this study. All patients were placed on an enteral nutrition regimen with Elental(R) (Ajinomoto pharmaceutical. Ltd., Tokyo, Japan). Serum selenium, zinc and copper concentrations were determined by atomic absorption spectroscopy. Serum selenoprotein P levels were determined by an ELISA system. Average serum levels of albumin, selenium, zinc and copper were 4.1 +/- 0.4 g/dl, 11.2 +/- 2.8 microg/dl, 71.0 +/- 14.8 microg/dl, and 112.0 +/- 25.6 microg/dl, respectively. In 9 patients of 31 CD patients, serum albumin levels were lower than the lower limit of the normal range. Serum selenium, zinc and copper levels were lower than lower limits in 12 patients, 9 patients and 1 patient, respectively. Serum selenium levels significantly correlated with both serum selenoprotein P levels and glutathione peroxidase activity. Supplementation of selenium (100 microg/day) and zinc (10 mg/day) for 2 months significantly improved the trace element status in CD patients. In conclusion, serum selenium and zinc levels are lower in many CD patients on long-term enteral nutrition. In these patients, supplementation of selenium and zinc was effective in improving the trace element status.

Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands.

Mitragynine (1) is a major alkaloidal component in the Thai traditional medicinal herb, Mitragyna speciosa, and has been proven to exhibit analgesic activity mediated by opioid receptors. By utilizing this natural product as a lead compound, synthesis of some derivatives, evaluations of the structure-activity relationship, and surveys of the intrinsic activities and potencies on opioid receptors were performed with guinea pig ileum. The affinities of some compounds for mu-, delta-, and kappa-receptors were determined in a receptor binding assay. The essential structural moieties in the Corynanthe type indole alkaloids for inducing the opioid agonistic activity were also clarified. The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an analgesic activity in the tail flick test in mice.