Optimal nutrition during the period of mechanical ventilation decreases mortality in critically ill, long-term acute female patients: a prospective observational cohort study

ABSTRACT: INTRODUCTION: Optimal nutrition for intensive care patients has been proposed to be the provision of energy as determined by indirect calorimetry, and protein provision of at least 1.2 grams/kg pre-admission weight per day. The evidence supporting these nutritional goals is based on surrogate outcomes and is not yet substantiated by patient oriented, clinically meaningful endpoints. In the present study we evaluated the effects of achieving optimal nutrition in intensive care unit (ICU) patients during their period of mechanical ventilation on mortality. METHODS: Prospective observational cohort study in a mixed medical-surgical, 28-bed intensive care unit in an academic hospital. 243 sequential mixed medical-surgical patients were enrolled on day 3 to 5 after admission if they had an expected stay of at least another 5 to 7 days. They underwent indirect calorimetry as part of routine care. Nutrition was guided by the result of indirect calorimetry and we aimed to provide at least 1.2 grams of protein/kg/day. Cumulative balances were calculated for the period of mechanical ventilation. Outcome parameters were ICU, 28-day and hospital mortality. RESULTS: In women, when corrected for weight, height, Apache II score, diagnosis category, and hyperglycaemic index, patients who reached their nutritional goals compared to those who did not, showed a hazard ratio (HR) of 0.199 for ICU mortality (confidence interval [CI] 0.048 - 0.831; P = 0.027), a HR of 0.079 for 28 day mortality (CI 0.013 - 0.467; P = 0.005) and a HR of 0.328 for hospital mortality (CI 0.113 - 0.952; P = 0.04). Achievement of energy goals whilst not reaching protein goals, did not affect ICU mortality; the HR for 28-day mortality was 0.120 (CI 0.027 - 0.528; P = 0.005) and 0.318 for hospital mortality (CI 0.107 - 0.945; P=0.039). No difference in outcome related to optimal feeding was found for men. CONCLUSIONS: Optimal nutritional therapy improves ICU, 28-day and hospital survival in female ICU patients. Female patients reaching both energy and protein goals have better outcomes than those reaching only the energy goal. In the present study men did not benefit from optimal nutritio

Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs

Background: Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet.Methods: Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study.Results: Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p < 0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p < 0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p < 0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p < 0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p < 0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R2= 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p < 0.05) in UF (571 ± 95) pigs.Conclusion: Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

The effect of carbohydrate and fat variation in euenergetic diets on postabsorptive free fatty acid release

Diet composition and energy content modulate free fatty acid (FFA) release. The aim of this study was to evaluate the dose-response effects of euenergetic variations in dietary carbohydrate and fat content on postabsorptive FFA release. The rate of appearance (R-a) of palmitate was measured by infusion of [2,2-H-2(2)]palmitate after an overnight fast in six healthy men on three separate occasions, i.e. after 7 d on euenergetic control, high-carbohydrate and high-fat diets. The protein content and composition was identical for each diet. Postabsorptive plasma fatty acid concentrations were not different between the high-carbohydrate and control diets (0.36 (se 0.07) v. 0.43 (se 0.04) mmol/l), but were increased after the high-fat diet (0.75 (se 0.09) mmol/l, (

Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity

Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito—early and late oocysts containing midgut sporozoites, and the mature, infectious salivary gland sporozoites. Despite the morphological similarity between midgut and salivary gland sporozoites, their proteomes are markedly different, in agreement with their increase in hepatocyte infectivity. The different sporozoite proteomes contain a large number of stage specific proteins whose annotation suggest an involvement in sporozoite maturation, motility, infection of the human host and associated metabolic adjustments. Analyses of proteins identified in the P. falciparum sporozoite proteomes by orthologous gene disruption in the rodent malaria parasite, P. berghei, revealed three previously uncharacterized Plasmodium proteins that appear to be essential for sporozoite development at distinct points of maturation in the mosquito. This study sheds light on the development and maturation of the malaria parasite in an Anopheles mosquito and also identifies proteins that may be essential for sporozoite infectivity to humans

A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency

A potential role for muscle in glucose homeostasis was recently suggested based on characterization of extrahepatic and extrarenal glucose-6-phosphatase (glucose-6-phosphatase-beta). To study the role of extrahepatic tissue in glucose homeostasis during fasting glucose kinetics were studied in two patients with a deficient hepatic and renal glycogenolysis and/or gluconeogenesis. Endogenous glucose production (EGP), glycogenolysis (GGL), and gluconeogenesis (GNG) were quantified with stable isotopes in a patient with glycogen storage disease type 1a (GSD-1a) and a patient with fructose-1,6-bisphosphatase (FBPase) deficiency. The [6,6-H-2(2)]glucose dilution method in combination with the deuterated water method was used during individualized fasting tests. Both patients became hypoglycemic after 2.5 and 14.5 h fasting, respectively. At that time, the patient with GSD-1a had EGP 3.84 mu mol/kg per min (30% of normal EGP after an overnight fast), GGL 3.09 mu mol/kg per min, and GNG 0.75 mu mol/kg per min. The patient with FBPase deficiency had EGP 8.53 mu mol/kg per min (62% of normal EGP after an overnight fast), GGL 6.89 mu mol/kg per min GGL, and GNG 1.64 mu mol/kg per min. EGP was severely hampered in both patients, resulting in hypoglycemia. However, despite defective hepatic and renal GNG in both disorders and defective hepatic GGL in GSD-1a, both patients were still able to produce glucose via both pathways. As all necessary enzymes of these pathways have now been functionally detected in muscle, a contribution of muscle to EGP during fasting via both GGL as well as GNG is suggeste

Hypoglycemia in falciparum malaria: is fasting an unrecognized and insufficiently emphasized risk factor?

Hypoglycemia is a frequently encountered complication in falciparum malaria that is usually ascribed to increased glucose use and impaired glucose production caused by the inhibition of gluconeogenesis. Here, in light of recent data showing that glucose production and gluconeogenesis are often increased in falciparum malaria, we review the causes and the risk factors leading to hypoglycemia in malaria. Fasting emerges as an important potential risk factor. Length of fasting should be included in studies on hypoglycemia in malaria. Full recognition of this risk factor for hypoglycemia in malaria could change both advice to the population, especially mothers, and treatment guidelines in the health secto