Effects of beta-hydroxy beta-methyl butyrate calcium combined with exercise therapy in patients with cardiac disease: a study protocol for clinical trial.

INTRODUCTION: The current treatment for heart disease consists of exercise therapy in addition to pharmacotherapy, nutritional support and lifestyle guidance. In general, nutritional support focuses on protein, salt and energy restrictions, with no active protein or amino acid intake in cases involving moderate or higher renal failure. From this perspective, patients with cardiac disease are at high risk of frailty.Beta-hydroxy beta-methyl butyrate (HMB) is a metabolite of leucine. HMB is widely used for muscle strengthening and can be safely ingested even by patients with renal failure. The proposed study protocol will investigate the effects of HMB-calcium (HMB-Ca) administered in combination with comprehensive cardiac rehabilitation for muscle strength, muscle mass and cardiac function in patients with cardiac disease during the convalescent period. The primary outcome will be knee extensor strength. Secondary outcomes will be gross isometric limb strength and skeletal muscle mass. METHODS AND ANALYSIS: This study will be a single-blinded, randomised, controlled trial with parallel comparisons between two groups. The study period will be 60 days from the start of outpatient cardiac rehabilitation. Participants will be randomly divided into two groups: an HMB group consuming HMB-Ca one time per day for 60 days; and a Placebo group consuming reduced maltose once one time per day for 60 days. Exercise therapy will be performed by both groups. ETHICS AND DISSEMINATION: The study protocol will be published in a peer-reviewed journal. Ethics approval was provided by the Showa University Clinical Research Review Board. TRIAL REGISTRATION NUMBER: jRCTs031220139; Japan Registry of Clinical Trails.

Effects of perioperative exercise therapy combined with nutritional supplementation on functional recovery after fast-track total hip arthroplasty.

BACKGROUND: The combination of exercise therapy combined with nutritional supplementation (Nutr) is widely used for frail or sarcopenic older persons. However, the effects of Nutr in elderly patients after fast-track total hip arthroplasty (THA) are unknown. This study examined the effects of perioperative Nutr on muscle strength, functional performance, and quality of life (QOL) in frail elderly women after fast-track THA. METHODS: A total of 58 frail elderly women aged 65-80 years scheduled for unilateral primary THA were randomly allocated to two groups: the physical exercise (Ex) combined with Nutr (Ex + Nutr; n = 29) group, and the Ex alone (Ex; n = 29) group. Protein and vitamin D supplements were provided daily from 4 weeks preoperatively to 8 weeks postoperatively (12 weeks) to the patients in the Ex + Nutr group, whereas the Ex group did not receive any supplements. Surgery and postoperative rehabilitation programmes during intervention were identical in both groups. Hip abductor and knee extensor muscle strength, functional performance (Timed Up & Go test, Harris Hip Score), and QOL (Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire) were assessed at baseline and at 12 weeks (8 weeks postoperatively). RESULTS: After the intervention, hip abductor muscle strength on the contralateral leg and knee extensor muscle strength on both sides significantly improved in the Ex + Nutr group compared to the Ex group (p = 0.03, 0.01, and 0.01, respectively). However, hip abductor muscle strength on the operated side did not differ significantly between the groups (p = 0.23). There were no significant differences in functional performance and QOL. CONCLUSION: Ex + Nutr does not have an additional effect on the improvement of hip abductor strength, functional performance, and QOL compared to Ex alone after fast-track THA. However, significant improvements were observed in the strength of some muscles after fast-track THA. TRIAL REGISTRATION: UMIN 000042964. THE IRB APPROVAL: This study was approved by the Mirai Iryo Reesearch Center (approval number TGE1602-115).

Examination of a nutritional treatment pathway according to pretreatment health status and stress levels of patients undergoing hematopoietic stem cell transplantation.

INTRODUCTION: This study aimed to validate hematopoietic stem cell transplantation (HSCT) treatment via a tailored nutritional pathway in myeloablative conditioning (MAC), determine its efficacy in terms of remission, and explore associations between clinical outcomes and nutritional indicators. METHODS: We included patients who underwent MAC for HSCT at the Shizuoka Cancer Center Stem Cell Transplantation between 2015 and 2019. We evaluated outcomes from the day before treatment initiation (transplant date: day 0) to day 42. RESULTS: Among the 40 MAC cases (participant characteristics: 20/40 males, mean age of 52 years, and mean body mass index of 21.9 kg/m2), we found that the percent loss of body weight and loss of skeletal muscle mass were correlated with the basal energy expenditure rate (BEE rate; r = 0.70, p<0.001 and r = 0.49, p<0.01, respectively). Based on the receiver operating characteristics curves, the cutoff value for the BEE rate in terms of weight loss was 1.1. Salivary amylase levels did not significantly change during the treatment course. Continuous variables, including oral caloric intake and performance status, showed statistically significant correlations with nutrition-related adverse events during treatment (r = -0.93, p<0.01 and r = 0.91, p<0.01, respectively). Skeletal muscle mass before treatment initiation was an independent predictive variable for reduced 2-year survival (p = 0.04). CONCLUSION: Our results support the validity of a safe nutritional pathway with a BEE rate of 1.1 for HSCT patients pretreated with MAC. Specifically, we found that this pathway could prevent weight loss in response to nutrition-related adverse events. Skeletal muscle mass before treatment was identified as an independent risk factor for reduced 2-year survival.

Risk factors for high-dose methotrexate-induced nephrotoxicity.

High-dose methotrexate (MTX) is widely used for the treatment of hematological malignancies. Despite the application of routine supportive care measures, such as intensive fluid hydration and urine alkalinization, nephrotoxicity is still a problem. The present study aimed to evaluate the risk factors for MTX-induced nephrotoxicity. We retrospectively reviewed 88 patients who received a regimen consisting of high-dose MTX (1000 mg/m2) and cytosine arabinoside between 2006 and 2018. Nephrotoxicity (≥ grade 2) was observed in 11 patients. Nephrotoxicity was observed only in patients with a high MTX concentration. Other than the MTX concentration, the serum uric acid level and urine pH at day 1 were associated with nephrotoxicity. A multivariate analysis revealed that urine pH was an independent risk factor for MTX-induced nephrotoxicity. Urine pH < 7.0 at day 1 was a significant risk factor for nephrotoxicity (odds ratio, 8.05; 95% confidence interval 1.95-33.3) and was also a predictor of delayed MTX elimination at 72 h after injection. Among pre-treatment factors, a low serum calcium level predicted urine pH < 7.0 at day 1. In conclusion, the present study suggests that low urine pH at day 1 is an independent risk factor for MTX-induced nephrotoxicity.

Neural Decoding of Multi-Modal Imagery Behavior Focusing on Temporal Complexity.

Mental imagery behaviors of various modalities include visual, auditory, and motor behaviors. Their alterations are pathologically involved in various psychiatric disorders. Results of earlier studies suggest that imagery behaviors are correlated with the modulated activities of the respective modality-specific regions and the additional activities of supramodal imagery-related regions. Additionally, despite the availability of complexity analysis in the neuroimaging field, it has not been used for neural decoding approaches. Therefore, we sought to characterize neural oscillation related to multimodal imagery through complexity-based neural decoding. For this study, we modified existing complexity measures to characterize the time evolution of temporal complexity. We took magnetoencephalography (MEG) data of eight healthy subjects as they performed multimodal imagery and non-imagery tasks. The MEG data were decomposed into amplitude and phase of sub-band frequencies by Hilbert-Huang transform. Subsequently, we calculated the complexity values of each reconstructed time series, along with raw data and band power for comparison, and applied these results as inputs to decode visual perception (VP), visual imagery (VI), motor execution (ME), and motor imagery (MI) functions. Consequently, intra-subject decoding with the complexity yielded a characteristic sensitivity map for each task with high decoding accuracy. The map is inverted in the occipital regions between VP and VI and in the central regions between ME and MI. Additionally, replacement of the labels into two classes as imagery and non-imagery also yielded better classification performance and characteristic sensitivity with the complexity. It is particularly interesting that some subjects showed characteristic sensitivities not only in modality-specific regions, but also in supramodal regions. These analyses indicate that two-class and four-class classifications each provided better performance when using complexity than when using raw data or band power as input. When inter-subject decoding was used with the same model, characteristic sensitivity maps were also obtained, although their decoding performance was lower. Results of this study underscore the availability of complexity measures in neural decoding approaches and suggest the possibility of a modality-independent imagery-related mechanism. The use of time evolution of temporal complexity in neural decoding might extend our knowledge of the neural bases of hierarchical functions in the human brain.

The Effects of Timing of a Leucine-Enriched Amino Acid Supplement on Body Composition and Physical Function in Stroke Patients: A Randomized Controlled Trial.

The combination of exercise and nutritional intervention is widely used for stroke patients, as well as frail or sarcopenic older persons. As previously shown, supplemental branched chain amino acids (BCAAs) or protein to gain muscle mass has usually been given just after exercise. This study investigated the effect of the timing of supplemental BCAAs with exercise intervention on physical function in stroke patients. The participants were randomly assigned to two groups based on the timing of supplementation: breakfast (n = 23) and post-exercise (n = 23). The supplement in the breakfast group was provided at 08:00 with breakfast, and in the post-exercise group it was provided just after the exercise session in the afternoon at 14:00-18:00. In both groups, the exercise intervention was performed with two sessions a day for two months. The main effects were observed in body fat mass (p = 0.02, confidence interval (CI): 13.2-17.7), leg press strength (p = 0.04, CI: 94.5-124.5), and Berg balance scale (p = 0.03, CI: 41.6-52.6), but no interaction with intake timing was observed. Although the effect of the timing of supplementation on skeletal muscle mass was similar in both groups, BCAA intake with breakfast was effective for improving physical performance and decreasing body fat mass. The results suggest that a combination of BCAA intake with breakfast and an exercise program was effective for promoting rehabilitation of post-stroke patients.

The maturation of the P1m component in response to voice from infancy to 3 years of age: A longitudinal study in young children.

INTRODUCTION: In the early development of human infants and toddlers, remarkable changes in brain cortical function for auditory processing have been reported. Knowing the maturational trajectory of auditory cortex responses to human voice in typically developing young children is crucial for identifying voice processing abnormalities in children at risk for neurodevelopmental disorders and language impairment. An early prominent positive component in the cerebral auditory response in newborns has been reported in previous electroencephalography and magnetoencephalography (MEG) studies. However, it is not clear whether this prominent component in infants less than 1 year of age corresponds to the auditory P1m component that has been reported in young children over 2 years of age. METHODS: To test the hypothesis that the early prominent positive component in infants aged 0 years is an immature manifestation of P1m that we previously reported in children over 2 years of age, we performed a longitudinal MEG study that focused on this early component and examined the maturational changes over three years starting from age 0. Five infants participated in this 3-year longitudinal study. RESULTS: This research revealed that the early prominent component in infants aged 3 month corresponded to the auditory P1m component in young children over 2 years old, which we had previously reported to be related to language development and/or autism spectrum disorders. CONCLUSION: Our data revealed the development of the auditory-evoked field in the left and right hemispheres from 0- to 3-year-old children. These results contribute to the elucidation of the development of brain functions in infants.

Effect of exercise therapy combined with branched-chain amino acid supplementation on muscle strength in elderly women after total hip arthroplasty: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Many patients develop a prolonged decrease of muscle strength after total hip arthroplasty (THA) despite their reconstructed hip joint. Physical exercise combined with branched-chain amino acid (BCAA) supplementation has been reported to improve muscle strength in elderly persons with sarcopenia. However, the effect of BCAA supplementation in patients after THA is unknown. This study examined the effects of BCAA supplementation combined with exercise therapy on the improvement of physical function in elderly patients after THA. METHODS AND STUDY DESIGN: The subjects were 31 elderly women who underwent THA. The participants were randomly assigned to two groups: BCAA (n=18) and control (n=13). The combined therapy was carried out for one month after THA. For the exercise intervention, a 3-set physical exercise program was conducted. For the nutritional intervention, the participants consumed 3.4 g of BCAA supplement or 1.2 g of starch immediately after the exercise intervention. RESULTS: BCAA supplementation combined with muscle strengthening exercises had a significant effect on knee extension strength of the contralateral side and on upper arm cross-sectional area. The improvement ratio of knee extension strength before and after intervention on the operated side was also significantly higher in the BCAA group. CONCLUSIONS: BCAA supplementation is effective for patients to improve the strength of some muscles when combined with physical exercises, but hip abductor muscle strength of the operated leg did not improve. A future study is needed to determine the efficacy of this combined therapy for hip abductor muscle strength.

Gamma-band auditory steady-state response after frontal tDCS: A double-blind, randomized, crossover study.

The effects of transcranial direct current stimulation (tDCS) likely depend on cortical N-methyl-D-aspartic acid (NMDA) neurotransmission; however, no previous studies have reported tDCS-mediated modulation of cortical NMDA neurotransmission in humans. The gamma-band auditory steady-state response (ASSR) to a 40 Hz stimulation likely reflects the integrity of cortical NMDA neurotransmission. The present study tested whether the effect of tDCS is reflected in gamma-band ASSRs during a 40 Hz stimulation. Using a double-blind, randomized, crossover study, we performed magnetoencephalography (MEG) and measured the ASSR in 24 healthy participants during 40 Hz of auditory stimulation after prefrontal tDCS (2 mA) or sham (i.e., placebo) treatment. Our results failed to reveal significant differences in any brain between the two conditions after the application of a frequency of approximately 40 Hz. Based on these results, the ASSR is an insufficient method to detect the effect of tDCS on cortical NMDA neurotransmission. Unexpectedly, the results revealed an enhanced beta-band event-related spectral perturbation (ERSP) in the left motor cortex after tDCS compared with that observed after the sham stimuli. Given that beta-band oscillations reflect many functions in motor cortices, the tDCS for the frontal areas had some effect on the left motor cortex while the participants were focusing on not pressing the button with their right index finger. An additional study with an adequate psychological task is necessary to draw a conclusion regarding this unexpected result.

Comparison of Nutrition-Related Adverse Events and Clinical Outcomes Between ICE (Ifosfamide, Carboplatin, and Etoposide) and MCEC (Ranimustine, Carboplatin, Etoposide, and Cyclophosphamide) Therapies as Pretreatment for Autologous Peripheral Blood Stem Cell Transplantation in Patients with Malignant Lymphoma.

BACKGROUND The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation. MATERIAL AND METHODS We enrolled patients who underwent autologous peripheral blood stem cell transplantation between 2007 and 2012. Outcomes were compared between ICE therapy (n=14) and MCEC therapy (n=14) in relation to nutrient balance, engraftment day, and length of hospital stay. In both groups, we compared the timing of nutrition-related adverse events with oral caloric intake, analyzed the correlation between length of hospital stay and duration of parenteral nutrition, and investigated the association between oral caloric intake and the proportion of parenteral nutrition energy in total calorie supply. Five-year survival was compared between the groups. RESULTS Compared with the MCEC group, the ICE group showed significant improvement in oral caloric intake, length of hospital stay, and timing of nutrition-related adverse events and oral calorie intake, but a delay in engraftment. Both groups showed a correlation between duration of parenteral nutrition and length of hospital stay (P=0.0001) and between oral caloric intake (P=0.0017) and parenteral nutrition energy sufficiency rate (r=-0.73, P=0.003; r=-0.76, P=0.002). Five-year survival was not significantly different between the groups (P=0.1355). CONCLUSIONS Our findings suggest that compared with MCEC therapy, ICE therapy improves nutrition-related adverse events and reduces hospital stay, conserving medical resources, with no significant improvement in long-term survival. The nutritional pathway may serve as a tool for objective evaluation of pretreatment for autologous peripheral blood stem cell transplantation.

Prevention of ventriculoperitoneal shunt complications after intraperitoneal urological surgeries.

PURPOSE: To evaluate perioperative management for the prevention of postoperative shunt infection and malfunction after intraperitoneal urological surgery in patients with myelodysplasia and a ventriculoperitoneal shunt. METHODS: From 2005 to 2015, 20 consecutive patients with myelodysplasia and a ventriculoperitoneal shunt who underwent intraperitoneal urological surgeries were managed with the same perioperative regimen. Intraperitoneal surgeries involved opening gastrointestinal tracts, including bladder augmentation by enterocystoplasty, creating continent catheterizable channels and Malone antegrade continent enema. We compared results with those from seven previous reports regarding postoperative shunt complications, surgical histories of previous shunt revisions, management of bacteriuria before surgery preoperative bowel preparation, antibiotic regimens, and duration of indwelling drain. RESULTS: Of 20 patients, 18 received prior shunt revisions, and 14 had positive urine culture before surgery that was managed with oral antibiotics. Thirteen patients underwent bladder augmentation with ileum, and one underwent augmentation with sigmoid colon. Nineteen patients underwent Malone antegrade continent enema using the appendix. All parenteral antibiotics were stopped on postoperative day 2.5. Mean duration of indwelling peritoneal drain was 2.7days. Mean follow-up period was 59.8months. Neither postoperative shunt infections nor intraperitoneal shunt malfunctions were recognized during follow-up period. CONCLUSIONS: This is the first study to evaluate postoperative ventriculoperitoneal shunt complications in patients with myelodysplasia who underwent intraperitoneal urological surgeries with a specific perioperative regimen. Shunt complications are greatly reduced by rigorous perioperative management, including preoperative control of bacteriuria, appropriate administration of prophylactic antibiotics, and early removal of intraperitoneal drains. LEVELS OF EVIDENCE: The type of study: Case series with no comparison group, IV.

Effects and feasibility of exercise therapy combined with branched-chain amino acid supplementation on muscle strengthening in frail and pre-frail elderly people requiring long-term care: a crossover trial.

This study examined the effects and feasibility of a twice-weekly combined therapy of branched-chain amino acids (BCAAs) and exercise on physical function improvement in frail and pre-frail elderly people requiring long-term care. We used a crossover design in which the combination of exercise and nutritional interventions was carried out twice a week during cycles A (3 months) and B (3 months) and the exercise intervention alone was performed during the washout period. The exercise intervention entailed the following 5 training sets: 3 sets of muscle training at 30% of maximum voluntary contraction, 1 set of aerobic exercise, and 1 set of balance training. For the nutritional intervention, 6 g of BCAAs or 6 g of maltodextrin was consumed 10 min before starting the exercise. We determined upper and lower limb isometric strength, performance on the Functional Reach Test (FRT) and the Timed Up and Go test, and activity level. In the comparison between the BCAA group and the control group after crossover, the improvement rates in gross lower limb muscle strength (leg press, knee extension) and FRT performance were significantly greater (by approximately 10%) in the BCAA group. In the comparison between different orders of BCAA administration, significant effects were shown for the leg press in both groups only when BCAAs were given. The combination of BCAA intake and exercise therapy yielded significant improvements in gross lower limb muscle strength and dynamic balance ability.

[A CASE OF SOLITARY ADRENAL TUMOR METASTASIZED FROM RECTAL CANCER].

Solitary adrenal metastasis of rectal cancer is comparatively rare condition and it is difficult to be diagnosed because it doesn't have any characteristic symptoms. We report a case of this type of adrenal tumor that could be figured out by tumor markers and the analysis of CT scan image. A 67-year-old man visited our department with the right adrenal tumor. He has a past medical history of rectal cancer and a low anterior resection was performed in 2011. After the surgery, he received adjuvant chemotherapy for 6 months. There has been no finding of recurrence or metastasis after chemotherapy. However, his follow-up abdominal CT in 2013 showed the right adrenal tumor which was 23 mm in diameter. Serum CEA level has also increased to 4.1 ng/ml, but there was no abnormal finding with hormonal study. The tumor size and CEA level gradually increased up to 46 mm in size and 10.4 ng/ml during 6 months. Enhanced CT also showed 39% at rate of absolute percentage wash out, which was not the finding of typical functional adrenal tumor. Based on these findings, we diagnosed that the origin of this adrenal tumor should be solitary metastasis of the rectal cancer. For the treatment of surgical procedure, we performed laparoscopic right adrenalectomy. The pathological finding showed adenocarcinoma, the origin of which was the previous rectal cancer. Six months have passed since the surgery, but CEA level still has remained normal range and neither finding of recurrence nor metastasis has been found.