The concept of aggressive nutrition therapy and clinical indication: A position paper.

Aggressive nutrition therapy is a nutritional management method that sets energy intake requirements by adding the amount of energy accumulated to energy consumption. It is used to treat patients with undernutrition and sarcopenia. However, evidence for aggressive nutrition therapy is insufficient, and validation through high-quality clinical research is essential. Therefore, this paper aimed to clarify the concept of aggressive nutrition therapy, present indications and contraindications; and describe the effects, limitations, and the need to individualize aggressive nutrition therapy for different pathological conditions. Aggressive nutrition therapy should be accompanied by the etiology of undernutrition, sarcopenia, and nutritional metabolism in various states. In addition to calculating nutritional requirements, the nutritional management methods of oral intake, tube feeding, and parenteral nutrition should be appropriately selected. A nutrition plan with the amount of energy accumulated should also be a vital issue. This position paper was authored by the Registered Dietitian Subcommittee of the Japanese Association of Rehabilitation Nutrition and was approved by the Japanese Association of Rehabilitation Nutrition.

Aggressive nutrition therapy in malnutrition and sarcopenia.

Aggressive nutrition therapy is essential to improve nutrition and function in patients with malnutrition and sarcopenia. Malnutrition and sarcopenia negatively affect functional recovery and activities of daily living. Nutrition improvement is associated with better functional recovery. Target energy intake in aggressive nutrition therapy is defined as total energy expenditure (TEE) plus the amount of energy accumulated. The amount of energy accumulation per 1 kg of body weight is generally 7500 kcal. If the goal is to gain 1 kg of weight over 30 d, TEE + 250 kcal is the target daily energy intake. Aggressive nutrition therapy is implemented using a rehabilitation nutrition care process, which consists of five steps: assessment and diagnostic reasoning, diagnosis, goal setting, intervention, and monitoring. Aggressive nutrition therapy sets clear goals using the Specific, Measurable, Achievable, Relevant, and Time-bound principles. The application and effect of aggressive nutrition therapy differs depending on the etiology and condition of malnutrition. Precachexia, short bowel syndrome, and older people with mild to moderate dementia are indications for aggressive nutrition therapy. Nevertheless, aggressive nutrition therapy is usually contraindicated in cases of refractory cachexia, acute disease or injury with severe inflammation, and bedridden patients with severe dementia and reduced activity. Aggressive nutrition therapy should be combined with aggressive exercise and rehabilitation. Enhanced nutritional therapy combined with rehabilitation in patients with cerebrovascular disease, hip fracture, or acute disease is recommended in the 2018 clinical practice guidelines for rehabilitation nutrition. Further evidence for aggressive nutrition therapy is however required.

Comprehensive Geriatric Assessment and Nutrition-Related Assessment: A Cross-Sectional Survey for Health Professionals.

(1) Background: It is important to assess physical and nutritional status using the Comprehensive Geriatric Assessment (CGA). However, the correlation between the CGA usage and nutritional-related assessments remain unclear. This study aims to clarify the correlation between the CGA usage and other nutritional-related assessments. (2) Methods: We conducted a questionnaire survey on clinical use of CGA, assessment of sarcopenia/sarcopenic dysphagia/cachexia, and defining nutritional goals/the Nutrition Care Process/the International Classification of Functioning, Disability, and Health (ICF)/the Kuchi⁻Kara Taberu Index. (3) Results: The number of respondents was 652 (response rate, 12.0%), including 77 who used the CGA in the general practice. The univariate analyses revealed that participants using the CGA tended to assess sarcopenia (P = 0.029), sarcopenic dysphagia (P = 0.001), and define nutritional goals (P < 0.001). Multivariate logistic regression analyses for the CGA usage revealed that using ICF (P < 0.001), assessing sarcopenia (P = 0.001), sarcopenic dysphagia (P = 0.022), and cachexia (P = 0.039), and defining nutritional goals (P = 0.001) were statistically significant after adjusting for confounders. (4) Conclusions: There are correlations between the use of CGA and evaluation of sarcopenia, sarcopenic dysphagia, and cachexia and nutritional goals.

Prostaglandin E-major urinary metabolite as a noninvasive surrogate marker for infantile necrotizing enterocolitis.

BACKGROUND: Early definitive diagnosis of necrotizing enterocolitis (NEC) based on Bell's staging criteria is difficult because there are few observable changes on abdominal imaging and blood chemistry tests at the onset of the disease. PURPOSE: To investigate whether prostaglandin E-2 major urinary metabolite (PGE-MUM) can be a useful surrogate marker reflecting the disease state and severity of NEC in infants. METHODS: Infants were enrolled in this study between January 2014 and December 2016. NEC diagnosis was based on Bell's staging criteria > Stage II or necrotic bowel observed at surgery. After diagnosis, PGE-MUM level was measured and compared with that of the other disease and healthy infant groups. RESULTS: Median PGE-MUM value was highest in the NEC group (576 [65-3672] µg/g•Cre/BSA × 1000), followed by the other disease group (94 [57-296] µg/g•Cre/BSA × 1000) and the healthy infant group (19 [10-44] µg/g•Cre/BSA × 1000) (sensitivity: 92.3%, specificity: 81.5%, accuracy: 85.0%; p < 0.01). PGE-MUM level correlated with improved status of NEC, length of necrotic intestine, and Bell's staging criteria. CONCLUSIONS: PGE-MUM level may be a useful surrogate biomarker reflecting the disease state of NEC. The method of urine sample collection is also advantageous, being noninvasive for infants. This is the first study reporting PGE-MUM level in NEC. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: LEVEL II.

Sarcopenia and cachexia evaluation in different healthcare settings: a questionnaire survey of health professionals.

BACKGROUND AND OBJECTIVES: The rates of sarcopenia and cachexia evaluations by different occupational groups at different settings are unclear. The objectives are to evaluate and compare the relative use of sarcopenia and cachexia evaluations among dietitians and associated healthcare professionals in a diverse range of settings. METHODS AND STUDY DESIGN: Participants were 4,621 members from the Japanese Association of Rehabilitation Nutrition. Settings included acute general wards, convalescent rehabilitation wards, long-term care wards, homecare service, and other settings. A questionnaire-based cross-sectional study was performed to evaluate assessments for sarcopenia and cachexia among dietitians and other professionals. Multiple comparisons based on Bonferroni method and logistic regression analysis were used. RESULTS: 718 (15.5%) answered the questionnaire. Data from 683 valid questionnaires were analyzed. Muscle strength, muscle mass, physical function, and cachexia were assessed by 53.4%, 51.1%, 53.4%, and 17.4% of dietitians. At convalescent rehabilitation wards, these rates were 81.8%, 62.0%, 82.5%, and 14.0%. The use of muscle strength and physical function evaluations was significantly lower among dietitians than among physical therapists and occupational therapists. The use of muscle mass and cachexia evaluations was not significantly different among the occupations. The use of muscle mass and strength evaluations was significantly higher in convalescent rehabilitation wards than in acute general wards, long-term care wards and facilities, and other settings, but not in homecare services. Cachexia evaluations were not significantly different between all settings. CONCLUSIONS: Raising the awareness of cachexia and sarcopenia among dietitians is a key issue, which should be addressed.

Impact of a multidisciplinary rehabilitation nutrition team on evaluating sarcopenia, cachexia and practice of rehabilitation nutrition.

BACKGROUND/AIMS: To determine whether the presence of a multidisciplinary rehabilitation nutrition team affects sarcopenia and cachexia evaluation and practice of rehabilitation nutrition. METHODS: A cross-sectional study using online questionnaire among members of the Japanese Association of Rehabilitation Nutrition (JARN) was conducted. Questions were related to sarcopenia and cachexia evaluation and practice of rehabilitation nutrition. RESULTS: 677 (14.7%) questionnaires were analysed. 44.5% reported that their institution employed a rehabilitation nutrition team, 20.2% conducted rehabilitation nutrition rounds and 26.1% conducted rehabilitation nutrition meetings. A total of 51.7%, 69.7%, 69.0% and 17.8% measured muscle mass, muscle strength, physical function and cachexia, respectively. For those with a rehabilitation nutrition team, 63.5%, 80.7%, 82.4% and 22.9% measured muscle mass, muscle strength, physical function and cachexia, respectively, whereas 46.7%, 78.0% and 78.1% of the respondents reported implementation of nutrition planning strategies in consideration of energy accumulation, rehabilitation training in consideration of nutritional status and use of dietary supplements, respectively. Multivariate logistic regression analysis showed that the use of a rehabilitation nutrition team independently affected sarcopenia evaluation and practice of rehabilitation nutrition but not cachexia evaluation. CONCLUSIONS: The presence of a multidisciplinary rehabilitation nutrition team increased the frequency of sarcopenia evaluation and practice of rehabilitation nutrition. J. Med. Invest. 64: 140-145, February, 2017.

Successful Endosonography-Guided Drainage of an Intra-Abdominal Abscess in a 1-Year-Old Infant.

Endoscopic ultrasound (EUS)-guided intervention has been established as a safe, effective and minimally invasive procedure for various diseases in adults, but there have been limited reports in pediatric patients. Herein, we report our experience with successful EUS-guided drainage of an intraabdominal abscess in a 1-year-old infant concomitant with disseminated intravascular coagulation. The abscess was punctured via the stomach using a standard, convex-type echoendoscope, and the patient's condition improved after naso-cystic catheter placement. Although the clinical course was complicated by delayed hemorrhage from the puncture site, the bleeding was successfully managed by endoscopic hemostasis using a standard forward-viewing endoscope.

Management of extremely low birth weight neonates with bowel obstruction within 2 weeks after birth.

PURPOSE: The majority of bowel obstructions in extremely low birth weight (ELBW) neonates are meconium-related ileus (MRI). ELBW neonates with bowel obstruction may recover by conservative treatment, but some do not. Considering the high surgical morbidity rates, unnecessary surgery should be avoided. We sought to identify a reasonable treatment strategy under these conditions. METHODS: ELBW neonates who started to have bowel obstruction with an unclear cause within 14 days of age were enrolled. The study period was from January 2009 to August 2011. The enrolled patients had daily Gastrografin(®) enemas until 14 days of age or until the obstruction resolved. If the obstruction lasted beyond around 14 days of age, the patient underwent surgical intervention. The clinical data of the patients were collected and analyzed. RESULTS: Fourteen patients were enrolled. Twelve patients had MRI, which resolved within 14 days without surgery. Two patients with persistent obstruction underwent surgery, and they were found to have Hirschsprung's disease and ileal volvulus, respectively. CONCLUSION: For ELBW neonates with bowel obstruction of unclear etiology, the early and frequent administration of a Gastrografin(®) enema is reasonable. Surgery should be considered if the obstruction lasts beyond approximately 14 days after birth.

An animal model study for tissue-engineered trachea fabricated from a biodegradable scaffold using chondrocytes to augment repair of tracheal stenosis.

INTRODUCTION: We have designed an engineered graft fabricated from a biodegradable scaffold using chondrocytes and applied this construct to augment repair of tracheal stenosis. This study investigated the feasibility of using such tissue-engineered airways with autologous chondrocytes in a rabbit model. MATERIAL AND METHODS: Chondrocytes were isolated and expanded from the auricular cartilage of New Zealand white rabbits, then seeded onto composite 3-layer scaffolds consisting of a collagen sheet, a polyglycolic acid mesh, and a copolymer (l-lactide/epsilon-caprolactone) coarse mesh. The engineered grafts were implanted into a 0.5 x 0.8-cm defect created in the midventral portion of the cervical trachea. Gelatin sponges that slowly released basic fibroblast growth factor (b-FGF) were then placed on the constructs, which were retrieved 1 or 3 months after implantation. RESULTS: The biodegradable scaffold seeded with chondrocytes could maintain airway structure up to 3 months after implantation. Tracheal epithelial regeneration occurred in the internal lumen of this composite scaffold. Three months after implantation, staining of the sections showed cartilage accumulation in the engineered tracheal wall. CONCLUSION: This composite biodegradable scaffold may be useful for developing engineered trachea. A gelatin sponge slowly releasing b-FGF might enhance chondrogenesis.

Survival in a neonate with complete urorectal septum malformation sequence after fetal vesico-amniotic shunting for a prominently dilated cloaca.

Complete urorectal septum malformation sequence (URSMS) is usually a lethal anomaly that is characterized by urethral obstruction, imperforate anus, ambiguous genitalia, renal agenesis or dysplasia, and mullerian duct maldevelopment. This anomaly is thought to be caused by the cessation of urorectal septum migration toward the caudal cloacal membrane. Teratogenic factors or a genetic abnormality is postulated as the etiology. To date, only 4 patients with URSMS have survived the neonatal period; however, 2 of these infants died before the age of 1 year. We report the survival in a case with complete URSMS who had moderate pulmonary hypoplasia and preserved left renal function. The cloacal remnant was dilated more than expected because the wall of the muscle layer was torn, perhaps in early fetal life, and timely placement of vesico-amniotic shunts prevented severe pulmonary hypoplasia caused by oligohydramnios.

Antenatally diagnosed giant multicystic dysplastic kidney resected during the neonatal period.

At 24 weeks of gestation, a fetus was suspected of having a huge intraabdominal cyst by fetal ultrasound. Multicystic dysplastic kidney (MCDK) was the most probable diagnosis; however, because a solid area was visualized in the large cystic lesion, a neoplasm of the kidney could not be ruled out. A 3529-g boy was born at 35 weeks of gestation by cesarean delivery. Eight days after birth, the tumor was resected. Histopathologic examination confirmed MCDK. The cause of MCDK in this patient was assumed to be ureteral obstruction in early fetal life. These findings suggested that the affected kidney had experienced mesenchyme-to-epithelium transition followed by interaction between the metanephric blastema and ureteral bud.

Human tracheal chondrocytes as a cell source for augmenting stenotic tracheal segments: the first feasibility study in an in vivo culture system.

INTRODUCTION: Construction of engineered respiratory tract using tissue-engineered cartilage has not yet been reported. In order to generate artificial trachea using human chondrocytes obtained from tracheal cartilage, we investigated whether human tracheal chondrocytes can act as a cell source to fabricate engineered airway patches to augment stenotic parts of the trachea. MATERIALS AND METHODS: After informed consent, chondrocytes were obtained from five patients who needed tracheal surgery. A small piece of resected tracheal cartilage was digested by collagenase type 2 for 3-4 h. This yielded chondrocytes, which were expanded in vitro and seeded onto biodegradable scaffolds; these were then implanted subcutaneously in athymic mice. The implanted constructs were retrieved 8 weeks later for histologic and biochemical analysis. RESULTS: In monolayer cultures, chondrocytes proliferated well, showing a 100- to 1,000-fold increase in 1 month. Once expanded, the cells lost their original morphological and biologic characteristics, but the engrafted scaffold showed histologic and biochemical characteristics of cartilage. Viable chondrocytes and extracellular matrix were detected, and glycosaminoglycan (GAG) in vivo was present. CONCLUSIONS: Here we show that a small piece of human tracheal cartilage can generate sufficient chondrocytes in vitro and form tracheal cartilage architecture in an in vivo environment.

Telangiectatic focal nodular hyperplasia of the liver in the perinatal period: case report.

We report a case of congenital telangiectatic focal nodular hyperplasia, a rare variant form of the disease. The patient was a 2-month-old boy whose parents noticed abdominal distention about 2 weeks after birth, and ultrasonogram revealed a large mass in the liver. He underwent right lobectomy, and gross findings showed an ill-defined mass without any central scar. Histologic findings demonstrated proliferating hepatocytes without atypia arranged in cords of 1- or 2-cell thickness with marked sinusoidal dilatation and extramedullary hematopoiesis. In addition, a significantly increased Ki-67 labeling index in the tumor compared with non-tumor liver cells, and cytogenetic analysis of 23 G-banded metaphase preparations revealed 3 abnormal karyotypes, suggesting hyperplastic or neoplastic features. To the best of our knowledge, the present case is only the third documented case of congenital telangiectatic focal nodular hyperplasia.

Efficient production of L-(+)-lactic acid from raw starch by Streptococcus bovis 148.

Streptococcus bovis 148 was found to produce L-(+)-lactic acid directly from soluble and raw starch substrates at pH 6.0. Productivity was highest at 37 degrees C, with 14.7 g/l lactic acid produced from 20 g/l raw starch. The yield and optical purity of L-lactic acid were 0.88 and 95.6%, respectively.

Dendritic cells stimulated with a bacterial product, OK-432, efficiently induce cytotoxic T lymphocytes specific to tumor rejection peptide.

Dendritic cells (DCs) are potent antigen-presenting cells, which have recently been applied for cancer immunotherapy using epitope peptides. Accumulating results of the clinical trials of such a strategy suggest that maturity of the applied DCs has a significant impact on the outcome of the vaccination. Here we examined the effects of penicillin-killed Streptococcus pyogenes (OK-432) on DC maturation and functions including induction of CTLs. DCs generated from peripheral blood using granulocyte macrophage colony-stimulating factor and interleukin (IL)-4 showed immunophenotypes consistent with immature DCs (iDCs). These iDCs were further incubated with medium alone, tumor necrosis factor alpha, lipopolysaccharide, or OK-432. The immunophenotypical analysis showed DCs stimulated with OK-432 (OK-DCs) possessed significantly higher expression of CD83 compared with unstimulated DCs. Furthermore, OK-DCs showed significantly higher production of IL-12 and IFN-gamma compared with DCs with other stimulations. These results indicate that OK-432 stimulates iDCs to have a mature phenotype and to produce a significant amount of T-helper 1-type cytokines. To examine the potency of OK-DCs on the induction of specific CTLs, the tumor rejection peptide derived from carcinoembryonic antigen was used as a model antigen. The HLA-tetramer assay showed that potent CTL was induced with OK-DCs at high frequency. These results indicate that OK-432 efficiently stimulates DCs without interfering with the presentation of pulsed peptide. Furthermore, OK-432 does not activate nuclear factor kappaB through Toll-like receptor 2 or Toll-like receptor 4 in the indicator cell system; however, it induces IL-12 production through the beta(2) integrin system on DCs. These results strongly suggest that OK-432 could be applied to develop an efficient cancer vaccine using DCs pulsed with tumor rejection peptides.