R. Fukushima

Growth Hormone and the Immune Response to Bacterial Infection

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1), especially the former, have immunoregulatory effects in addition to anabolic effects. The hormones may act to protect the host from lethal bacterial infection by promoting the maturation of myeloid cells, stimulating phagocyte migration, priming phagocytes for the production of superoxide anions and cytokines, and enhancing opsonic activity. GH administration may be beneficial for the prevention, as well as treatment, of severe sepsis in critical illness.

Preoperative total parenteral nutrition influences postoperative systemic cytokine responses after colorectal surgery

Previous human studies have investigated the influences of nutritional routes on the serum kinetics of cytokines following intravenous administration of lipopolysaccharide. However, it is unclear whether preoperative nutritional routes influence responses of systemic cytokines in patients after surgery. This study was designed to investigate whether preoperative total parental nutrition (TPN) influences systemic interleukin-6 (IL-6) and interleukin-8 (IL-8) responses in patients following surgery for colorectal cancer. Patients with colorectal cancer received TPN (TPN group, n = 6) or an oral diet (oral group n = 6) for more than 7 d before the operation. Patients in the TPN group received standard TPN. Patients in the oral group received an ordinary hospital diet. Blood samples were collected before the operation, on postoperative day 1 (POD1), POD3, and POD7. Levels of IL-6, IL-8, and C-reactive protein (CRP) in plasma were determined. The characteristics of patients in the TPN and oral groups were comparable. Mean carbohydrate intake was greater (28 versus 19 kCal/kg), and lipid intake was smaller (0 versus 7 kCal/kg) in the TPN group than in the oral group. Plasma CRP levels did not differ between the two groups. Plasma IL-6 and IL-8 levels were marginally higher before the operation and were significantly higher on POD1 in the TPN group than in the oral group. The IL-6 levels showed a positive regression relation with the amounts of blood loss only in the TPN group (P < 0.05, r = 0.881). The slope of the regression line was steeper in the TPN group than in the total enteral nutrition (TEN) group (P < 0.01). In conclusion, routes of nutritional supply have an impact on the production of systemic cytokines after insult. The postoperative systemic IL-6 and IL-8 responses in patients who received standard TPN preoperatively were greater than in patients who received an oral diet. Preoperative nutrition via the enteral route may provide better regulation of cytokine responses after surgery than parenteral nutrition.

Effects of three inhibitors of nitric oxide synthase on host resistance to bacterial infection.

Objective: To examine the effects of three nitric oxide synthase inhibitors on survival in a murine sepsis model.Design: Prospective randomized experimental trials.Setting: Laboratory.Subjects: Female Balb/c mice.Interventions:Escherichia coli (108 colony-formingunits/body) were injected into the peritoneal cavities of Balb/c mice. NG-nitro-L-arginine-methyl-ester, NG-monomethyl-L-arginine, or N-iminoethyl-L-ornithine was given at various concentrations, intraperitoneally, one hour before bacterial challenge.Measurements: One hundred and fifteen animals were observed for survival.Results: These inhibitors provided the mice no protection from the bacterial challenge. Notably, pretreatment with NG-nitro-L-arginine-methyl-ester (100 mg/kg i.p.) actually reduced survival time afterE. coli challenge.Conclusions: Inhibition of nitric oxide production improved neither the survival time nor rate in this murine sepsis model.

Marked and prolonged depression of Factor XIII after esophageal resection

Anastomotic leakage is one of the most common complications of esophagectomy and, since Factor XIII is required for normal wound healing, we investigated the temporal changes in plasma Factor XIII following esophagectomy and hepatectomy. A control group of patients undergoing other abdominal operations was also studied. Factor XIII activity was determined before surgery and on postoperative days (POD) 1, 3, 7 and 14. The plasma levels of acute phase protein were also measured. The plasma Factor XIII activity decreased significantly in both the hepatectomy and control groups until POD 7, reaching the lowest level on POD 3. In contrast, the esophagectomy group showed significant decreases in Factor XIII levels throughout the postoperative study period, with a nadir with an average activity of 56 per cent on POD 7. Preoperative transferrin levels had a positive correlation with Factor XIII levels measured on POD 3 and there was also a positive significant correlation between Factor XIII activity and alpha 2-macroglobulin levels on POD 3. These results suggest that there is a marked and prolonged depression of plasma Factor XIII activity following esophagectomy which may be attributed to accelerated tissue demands, inadequate synthesis or increased degradation. Moreover, the severe and sustained decrease in Factor XIII activity may be related to poor wound healing after esophagectomy.

Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis

The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.

Health insurance or subsidy has universal advantage for management of hospital malnutrition unrelated to GDP

BACKGROUND AND OBJECTIVES Protein-energy and micronutrient malnutrition are global public health problems which, when not prevented and severe, require medical management by clinicians with nutrition expertise, preferably as a collectively skilled team, especially when disease-related. This study aimed to investigate barriers and facilitators of clinical nutrition services (CNS), especially the use of oral, enteral (EN) and parenteral (PN) nutrition in institutional and home settings. METHODS AND STUDY DESIGN An international survey was performed between January and December 2014 in twenty-six countries from all continents. Electronic questionnaires were distributed to 28 representatives of clinical nutrition (PEN) societies, 27 of whom responded. The questionnaire comprised questions regarding a countrys economy, reimbursement for CNS, education about and the use of EN and PN. RESULTS The prevalence of malnutrition was not related to gross domestic product (GDP) at purchasing power parity (PPP) per capita (p=0.186). EN and PN were used in all countries surveyed (100%), but to different extents. Reimbursement of neither EN nor PN use depended on GDP, but was associated with increased use of EN and PN in hospitals (p=0.035), although not evident for home or chronic care facilities. The size of GDP did not affect the use of EN (p=0.256), but it mattered for PN (p=0.019). CONCLUSIONS A worldwide survey by nutrition support societies did not find a link between national economic performance and the implementation of medical nutrition services. Reimbursement for CNS, available through health insurance systems, is a factor in effective nutrition management.

GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community

BACKGROUND This initiative aims to build a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS The Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS A 2-step approach for the malnutrition diagnosis was selected, that is, first screening to identify at risk status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among GLIM participants that selected 3 phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and 2 etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least 1 phenotypic criterion and 1 etiologic criterion should be present. Phenotypic metrics for grading severity are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSIONS A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The construct should be re-considered every 3-5 years.