You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Whole body protein kinetics during hypocaloric and normocaloric feeding in critically ill patients
Abstract 1:
Introduction Optimal feeding of critically ill patients in the ICU is controversial . Existing guidelines rest on rather weak evidence . Whole body protein kinetics may be an attractive technique for assessing optimal protein intake . In this study , critically ill patients were investigated during hypocaloric and normocaloric IV nutrition . Methods Neurosurgical patients on mechanical ventilation ( n = 16 ) were studied during a 48-hour period . In r and om order 50 % and 100 % of measured energy expenditure was given as IV nutrition during 24 hours , corresponding to hypocaloric and normocaloric nutrition , respectively . At the end of each period , whole body protein turnover was measured using d5-phenylalanine and 13C-leucine tracers . Results The phenylalanine tracer indicated that whole-body protein synthesis was lower during hypocaloric feeding , while whole-body protein degradation and amino acid oxidation were unaltered , which result ed in a more negative protein balance , namely −1.9 ± 2.1 versus −0.7 ± 1.3 mg phenylalanine/kg/h ( P = 0.014 ) . The leucine tracer indicated that whole body protein synthesis and degradation and amino acid oxidation were unaltered , but the protein balance was negative during hypocaloric feeding , namely −0.3 ± 0.5 versus 0.6 ± 0.5 mg leucine/kg/h ( P < 0.001 ) . Conclusion In the patient group studied , hypocaloric feeding was associated with a more negative protein balance , but the amino acid oxidation was not different . The protein kinetics measurements and the study ’s investigational protocol were useful for assessing the efficacy of nutrition support on protein metabolism in critically ill patients


Title 2:
Moderate glucose control results in less negative nitrogen balances in medical intensive care unit patients: a randomized, controlled study
Abstract 2:
Introduction Hyperglycemia and protein loss are common in critically ill patients . Insulin can be used to lower blood glucose and inhibit proteolysis . The impact of moderate insulin therapy on protein metabolism in critically ill patients has not been evaluated . We compared urinary nitrogen excretion , nitrogen balance , serum albumin concentrations , prealbumin concentrations , and clinical outcomes between patients receiving moderate insulin therapy ( MIT ) and conventional insulin therapy ( CIT ) in a medical ICU . Methods Patients were r and omly divided into groups and treated with MIT ( glucose target 120 to 140 mg/dl ) or CIT ( glucose target 180 to 200 mg/dl ) . Calories and protein intake were recorded each day . On days 3 , 7 and 14 , the 24-hour urinary nitrogen excretion , nitrogen balance , and serum albumin and prealbumin concentrations were measured . Clinical outcomes data were collected . Results A total of 112 medical ICU patients were included , with 55 patients r and omized to the MIT group and 57 patients r and omized to the CIT group . Patients treated with MIT showed a trend towards increased nitrogen balance ( P = 0.070 ) , significantly lower urinary nitrogen excretion ( P = 0.027 ) , and higher serum albumin ( P = 0.047 ) and prealbumin ( P = 0.001 ) concentrations than patients treated with CIT . The differences between the two groups were most significant on day 3 , when all factors showed significant differences ( P < 0.05 ) . Conclusions Moderate glucose control results in less negative nitrogen balances in medical ICU patients . Differences are more significant in the early stages compared with the late stages of critical illness . Trial registration Clinical Trial . Gov


Title 3:
Early versus late parenteral nutrition in critically ill adults.
Abstract 3:
BACKGROUND Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets can not be met by enteral nutrition alone . METHODS In this r and omized , multicenter trial , we compared early initiation of parenteral nutrition ( European guidelines ) with late initiation ( American and Canadian guidelines ) in adults in the intensive care unit ( ICU ) to supplement insufficient enteral nutrition . In 2312 patients , parenteral nutrition was initiated within 48 hours after ICU admission ( early-initiation group ) , whereas in 2328 patients , parenteral nutrition was not initiated before day 8 ( late-initiation group ) . A protocol for the early initiation of enteral nutrition was applied to both groups , and insulin was infused to achieve normoglycemia . RESULTS Patients in the late-initiation group had a relative increase of 6.3 % in the likelihood of being discharged alive earlier from the ICU ( hazard ratio , 1.06 ; 95 % confidence interval [ CI ] , 1.00 to 1.13 ; P=0.04 ) and from the hospital ( hazard ratio , 1.06 ; 95 % CI , 1.00 to 1.13 ; P=0.04 ) , without evidence of decreased functional status at hospital discharge . Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups . Patients in the late-initiation group , as compared with the early-initiation group , had fewer ICU infections ( 22.8 % vs. 26.2 % , P=0.008 ) and a lower incidence of cholestasis ( P<0.001 ) . The late-initiation group had a relative reduction of 9.7 % in the proportion of patients requiring more than 2 days of mechanical ventilation ( P=0.006 ) , a median reduction of 3 days in the duration of renal-replacement therapy ( P=0.008 ) , and a mean reduction in health care costs of € 1,110 ( about $ 1,600 ) ( P=0.04 ) . CONCLUSIONS Late initiation of parenteral nutrition was associated with faster recovery and fewer complications , as compared with early initiation . ( Funded by the Methusalem program of the Flemish government and others ; EPaNIC Clinical Trials.gov number , NCT00512122 . )


Title 4:
Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial.
Abstract 4:
BACKGROUND Patients who are critically ill can develop so-called intensive-care unit acquired weakness , which delays rehabilitation . Reduced muscle mass , quality , or both might have a role . The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients ( EPaNIC ) trial ( registered with Clinical Trials.gov , number NCT00512122 ) showed that tolerating macronutrient deficit for 1 week in intensive-care units ( late parenteral nutrition [ PN ] ) accelerated recovery compared with early PN . The role of weakness was unclear . Our aim was to assess whether late PN and early PN differentially affect muscle weakness and autophagic quality control of myofibres . METHODS In this prospect ively planned sub analysis of the EPaNIC trial , weakness ( MRC sum score ) was assessed in 600 awake , cooperative patients . Skeletal muscle biopsies , harvested from 122 patients 8 days after r and omisation and from 20 matched healthy controls , were studied for autophagy and atrophy . We determined the significance of differences with Mann-Whitney U , Median , Kruskal-Wallis , or χ(2 ) ( exact ) tests , as appropriate . FINDINGS With late PN , 105 ( 34 % ) of 305 patients had weakness on first assessment ( median day 9 post-r and omisation ) compared with 127 ( 43 % ) of 295 patients given early PN ( absolute difference -9 % , 95 % CI -16 to -1 ; p=0·030 ) . Weakness recovered faster with late PN than with early PN ( p=0·021 ) . Myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls , similarly with early PN and late PN . The LC3 ( microtubule-associated protein light chain 3 ) II to LC3I ratio , related to autophagosome formation , was higher in patients given late PN than early PN ( p=0·026 ) , reaching values almost double those in the healthy control group ( p=0·0016 ) , and coinciding with less ubiquitin staining ( p=0·019 ) . A higher LC3II to LC3I ratio was independently associated with less weakness ( p=0·047 ) . Expression of mRNA encoding contractile myofibrillary proteins was lower and E3-ligase expression higher in muscle biopsies from patients than in control participants ( p≤0·0006 ) , but was unaffected by nutrition . INTERPRETATION Tolerating a substantial macronutrient deficit early during critical illness did not affect muscle wasting , but allowed more efficient activation of autophagic quality control of myofibres and reduced weakness . FUNDING UZ Leuven , Research Foundation-Fl and ers , the Flemish Government , and the European Research Council


Title 5:
Amino Acid Concentrations in Critically Ill Children Following Cardiac Surgery*
Abstract 5:
Objective : Guidelines for administering amino acids to critically ill children are largely based on uncontrolled observational studies and expert opinion , without support from rigorous outcome studies . Also , data on circulating amino acid concentrations during critical illness are scarce . We thoroughly studied the time profiles of circulating amino acid concentrations in critically ill children who received st and ard nutritional care according to international guidelines . Design : This is a sub analysis of pediatric critically ill patients included in a large ( n = 700 ) r and omized controlled study on intensive insulin therapy .  Setting : The study was conducted at a university hospital PICU . Patients : We studied 100 patients in PICU for at least 3 days following cardiac surgery . Interventions : Patients were assigned to intensive insulin therapy targeting normal-for-age fasting blood glucose concentrations or insulin infusion only to prevent excessive hyperglycemia . Measurements and Main Results : Plasma amino acid concentrations were measured at admission , day 3 , and day 7 in PICU . At admission , the concentrations of most amino acids were comparable to those reported for healthy children . Total amino acid concentrations remained stable during ICU stay , but individual amino acids showed different time profiles with eight of them showing an increase and five a decrease . Nonsurviving children had higher total amino acid concentrations and individual amino acids compared with survivors at admission and /or during ICU stay . Intensive insulin therapy lowered the concentrations of total amino acids and several individual amino acids . Neonates showed somewhat different amino acid profiles with rather increased concentrations from baseline with time in ICU for total amino acids and several individual amino acids as compared with older infants and children . Conclusions : Circulating amino acid concentrations in critically ill children after cardiac surgery differ according to survival status , blood glucose control with intensive insulin therapy , and age
Gielen et al ( 4 ) hypothesized that higher amino acid concentration profiles could be a sign of hypercatabolism , but no other measurements of protein balance or other nutritional comparison were considered , bar the assessment of body mass index .
It is well documented that patients who undergo cardiopulmonary bypass similar to other critically ill patients have hypercatabolism as a result of complex neuroendocrine responses ( 1 , 3 ) .
The hormonal and metabolic responses to cardiopulmonary bypass are greater in neonates compared with older children and adults due to a variety of metabolic and physical changes after birth .
It was observed that there is a strong association between malnutrition and poor wound healing , impaired immunity , increased risk of postoperative pneumonia , loss of skeletal muscle , and in patients after cardiac surgery additional loss of myocardial muscle , thus a complete and sequential nutritional evaluation should be performed ( 1 ) .