***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Despite extensive use of enteral ( EN ) and parenteral nutrition ( PN ) in intensive care unit ( ICU ) population s for 4 decades , evidence to support their efficacy is extremely limited . METHODS A prospect i ve r and omized trial was conducted evaluate the impact on outcomes of intensive medical nutrition therapy ( IMNT ; provision of > 75 % of estimated energy and protein needs per day via EN and adequate oral diet ) from diagnosis of acute lung injury ( ALI ) to hospital discharge compared with st and ard nutrition support care ( SNSC ; st and ard EN and ad lib feeding ) . The primary outcome was infections ; secondary outcomes included number of days on mechanical ventilation , in the ICU , and in the hospital and mortality . RESULTS Overall , 78 patients ( 40 IMNT and 38 SNSC ) were recruited . No significant differences between groups for age , body mass index , disease severity , white blood cell count , glucose , C-reactive protein , energy or protein needs occurred . The IMNT group received significantly higher percentage of estimated energy ( 84.7 % vs 55.4 % , P < .0001 ) and protein needs ( 76.1 vs 54.4 % , P < .0001 ) per day compared with SNSC . No differences occurred in length of mechanical ventilation , hospital or ICU stay , or infections . The trial was stopped early because of significantly greater hospital mortality in IMNT vs SNSC ( 40 % vs 16 % , P = .02 ) . Cox proportional hazards models indicated the hazard of death in the IMNT group was 5.67 times higher ( P = .001 ) than in the SNSC group . CONCLUSIONS Provision of IMNT from ALI diagnosis to hospital discharge increases mortality BACKGROUND Nutritional support has been recognized as an essential part of intensive care unit management . However , the appropriate caloric intake for critically ill patients remains ill defined . OBJECTIVE We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy ( IIT ) compared with that of conventional insulin therapy ( CIT ) on the outcomes of critically ill patients . DESIGN This study had a 2 × 2 factorial , r and omized , controlled design . Eligible patients were r and omly assigned to permissive underfeeding or target feeding groups ( caloric goal : 60 - 70 % compared with 90 - 100 % of calculated requirement , respectively ) with either IIT or CIT ( target blood glucose : 4.4 - 6.1 compared with 10 - 11.1 mmol/L , respectively ) . RESULTS Twenty-eight-day all-cause mortality was 18.3 % in the permissive underfeeding group compared with 23.3 % in the target feeding group ( relative risk : 0.79 ; 95 % CI : 0.48 , 1.29 ; P = 0.34 ) . Hospital mortality was lower in the permissive underfeeding group than in the target group ( 30.0 % compared with 42.5 % ; relative risk : 0.71 ; 95 % CI : 0.50 , 0.99 ; P = 0.04 ) . No significant differences in outcomes were observed between the IIT and CIT groups . CONCLUSION In critically ill patients , permissive underfeeding may be associated with lower mortality rates than target feeding . This trial was registered at controlled-trials.com as IS RCT N96294863 Summary Priming of the gastrointestinal ( GI ) tract with low-volume feedings before giving full enteral feedings to very premature , high-risk infants is a controversial practice . We design ed a study of infants weighing less than 1,250 g and receiving total parenteral nutrition to determine whether GI priming would hasten weight gain , improve tolerance of subsequent feedings , enhance nutritional status , and increase serum concentration of gastrin , a hormone trophic for intestinal growth . Infants were r and omly assigned to receive total parenteral nutrition ( TPN ) alone ( N = 21 ) or GI priming plus TPN ( N = 19 ) for 12 days beginning on day 3 of life . Full-strength premature infant formula was used for priming . Both groups received the same total nutrition . Beginning on day 15 , feedings in both groups were increased daily to a maximum of 120 kcal/kg/day on day 20 , where they were maintained until day 30 . After day 30 , the feedings were modified according to the infants ' condition . The groups did not differ in birth weight , gestational age , or 5-min Apgar scores . GI-primed infants had improved feeding tolerance after day 20 and a faster rise in serum gastrin during the initial phase of the study . There was no significant difference in weight gain . GI priming improves tolerance of feedings , accelerates rate of rise of serum gastrin during the first weeks of life , and does not increase the risk of feeding complications when compared to TPN alone . This may lead to more rapid maturation of the GI tract in primed infants BACKGROUND Enteral nutrition ( EN ) is recommended for patients in the intensive-care unit ( ICU ) , but it does not consistently achieve nutritional goals . We assessed whether delivery of 100 % of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition ( SPN ) could optimise clinical outcome . METHODS This r and omised controlled trial was undertaken in two centres in Switzerl and . We enrolled patients on day 3 of admission to the ICU who had received less than 60 % of their energy target from EN , were expected to stay for longer than 5 days , and to survive for longer than 7 days . We calculated energy targets with indirect calorimetry on day 3 , or if not possible , set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men , respectively . Patients were r and omly assigned ( 1:1 ) by a computer-generated r and omisation sequence to receive EN or SPN . The primary outcome was occurrence of nosocomial infection after cessation of intervention ( day 8) , measured until end of follow-up ( day 28 ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00802503 . FINDINGS We r and omly assigned 153 patients to SPN and 152 to EN . 30 patients discontinued before the study end .  Mean energy delivery between day 4 and 8 was 28 kcal/kg per day ( SD 5 ) for the SPN group ( 103 % [ SD 18 % ] of energy target ) , compared with 20 kcal/kg per day ( 7 ) for the EN group ( 77 % [ 27 % ] ) . Between days 9 and 28 , 41 ( 27 % ) of 153 patients in the SPN group had a nosocomial infection compared with 58 ( 38 % ) of 152 patients in the EN group ( hazard ratio 0·65 , 95 % CI 0·43 - 0·97 ; p=0·0338 ) , and the SPN group had a lower mean number of nosocomial infections per patient ( -0·42 [ -0·79 to -0·05 ] ; p=0·0248 ) . INTERPRETATION Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient . FUNDING Foundation Nutrition 2000Plus , ICU Quality Funds , Baxter , and Fresenius Kabi CONTEXT Responses to critical illness , such as excessive inflammation and hyperglycemia , may trigger detrimental chain reactions that damage cellular proteins and organelles . Such responses to illness contribute to the risk of ( nonresolving ) multiple organ dysfunction and adverse outcome . OBJECTIVE We studied autophagy as a bulk degradation pathway able to remove toxic protein aggregates and damaged organelles and how these are affected by preventing hyperglycemia with insulin during critical illness . DESIGN AND SETTING Patients participated in a r and omized study , conducted at a university hospital surgical/medical intensive care unit . PATIENTS We studied adult prolonged critically ill patients vs. controls . INTERVENTIONS Tolerating excessive hyperglycemia was compared with intensive insulin therapy targeting normoglycemia . MAIN OUTCOME MEASURES We quantified (ultra)structural abnormalities and hepatic and skeletal muscle protein levels of key players in autophagy . RESULTS Morphologically , both liver and muscle revealed an autophagy-deficiency phenotype . Proteins involved in initiation and elongation steps of autophagy were induced 1.3- to 6.5-fold by critical illness ( P ≤ 0.01 ) , but mature autophagic vacuole formation was 62 % impaired ( P = 0.05 ) and proteins normally de grade d by autophagy accumulated up to 97-fold ( P ≤ 0.03 ) . Mitophagy markers were unaltered or down-regulated ( P = 0.05 ) . Although insulin  preserved hepatocytic mitochondrial integrity ( P = 0.05 ) , it further reduced the number of autophagic vacuoles by 80 % ( P = 0.05 ) . CONCLUSIONS Insufficient autophagy in prolonged critical illness may cause inadequate removal of damaged proteins and mitochondria . Such incomplete clearance of cellular damage , inflicted by illness and aggravated by hyperglycemia , could explain lack of recovery from organ failure in prolonged critically ill patients . These data open perspectives for therapies that activate autophagy during critical illness Objective : To determine whether nutrient intake by early enteral nutrition with parenteral nutrition improves levels of retinol-binding protein and prealbumin ( primary endpoint ) and reduce morbidity and mortality ( secondary endpoint ) in ICU patients . Design : Prospect i ve , double-blind , and r and omized , placebo-controlled study . Setting : Two intensive care units in a tertiary institution . Patients and participants : 120 patients in two groups of 60.¶ Interventions : Patients received either enteral plus parenteral nutrition ( treatment group ) or enteral nutrition plus placebo ( placebo group ) for 4–7 days after initiation of nutritional support . Measurements and results : Retinol-binding protein ( P = 0.0496 ) and prealbumin ( P = 0.0369 ) increased significantly in the treatment group from day 0 to day 7 . There was no reduction in morbidity in ICU . There was no difference in OMEGA score ( 263 vs. 244 ) and length of stay in the ICU ( 16.9 vs. 17.3 ) , but a reduction in length of stay at hospital ( 31.2 ± 18.5 vs. 33.7 ± 27.7 , P = 0.0022 ) . Mortality on day 90 ( 17 vs. 18 ) and after 2 years ( 24 vs. 24 ) was identical . Conclusions : Although it enhances nutrient intake and corrects nutritional parameters such as RBP and prealbumin more rapidly , within 1 week , supplemental parenteral nutrition has no clinical ly relevant effect on outcome in ICU patients at the early phase of nutritional support BACKGROUND Proper caloric intake goals in critically ill surgical patients are unclear . It is possible that overnutrition can lead to hyperglycemia and an increased risk of infection . OBJECTIVE This study was conducted to determine whether surgical infection outcomes in the intensive care unit ( ICU ) could be improved with the use of hypocaloric nutritional support . DESIGN Eighty-three critically ill patients were r and omly allocated to receive either the st and ard calculated daily caloric requirement of 25 - 30 kcal · kg(-1 ) · d(-1 ) ( eucaloric ) or 50 % of that value ( hypocaloric ) via enteral tube feeds or parenteral nutrition , with an equal protein allocation in each group ( 1.5 g · kg(-1 ) · d(-1 ) ) . RESULTS There were 82 infections in the hypocaloric group and 66 in the eucaloric group , with no significant difference in the mean ( ± SE ) number of infections per patient ( 2.0 ± 0.6 and 1.6 ± 0.2 , respectively ; P = 0.50 ) , percentage of patients acquiring infection [ 70.7 % ( 29 of 41 ) and 76.2 % ( 32 of 42 ) , respectively ; P = 0.57 ] , mean ICU length of stay ( 16.7 ± 2.7 and 13.5 ± 1.1 d , respectively ; P = 0.28 ) , mean hospital length of stay ( 35.2 ± 4.9 and 31.0 ± 2.5 d , respectively ; P = 0.45 ) , mean 0600 glucose concentration ( 132 ± 2.9 and 135 ± 3.1 mg/dL , respectively ; P = 0.63 ) , or number of mortalities [ 3 ( 7.3 % ) and 4 ( 9.5 % ) , respectively ; P = 0.72 ] . Further analyses revealed no differences when analyzed by sex , admission diagnosis , site of infection , or causative organism . CONCLUSIONS Among critically ill surgical patients , caloric provision across a wide acceptable range does 
    Output:
    
The initial administration of low- versus high-energy supplements did not impact clinical outcomes except for gastrointestinal intolerance in non-malnourished critically ill patients receiving enteral nutrition .
The initial administration of highrather than low-energy may benefit these patients by reducing infections , but this effect might actually be attributable to the concomitant high protein intake