***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: Introduction Sepsis is associated with the generation of oxygen free radicals and ( lacking ) decreased selenium plasma concentrations . High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes . We investigated the effects of a continuous administration of high doses of selenium in septic shock patients . Methods A prospect i ve , multicentre , placebo-controlled , r and omized , double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection . Patients received , for 10 days , selenium as sodium selenite ( 4,000 μg on the first day , 1,000 μg/day on the nine following days ) or matching placebo using continuous intravenous infusion . The primary endpoint was the time to vasopressor therapy withdrawal . The duration of mechanical ventilation , the mortality rates in the intensive care unit , at hospital discharge , and at 7 , 14 , 28 and 180 days and 1 year after r and omization , and adverse events were recorded . Results Sixty patients were included ( placebo , n = 29 ; selenium , n = 31 ) .  The median time to vasopressor therapy withdrawal was 7 days in both groups ( 95 % confidence interval = 5–8 and 6–9 in the placebo and selenium groups , respectively ; log-rank , P = 0.713 ) . The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups , respectively ( P = 0.762 ) . Mortality rates did not significantly differ between groups at any time point . Rates of adverse events were similar in the two groups . Conclusion Continuous infusion of selenium as sodium selenite ( 4,000 μg on the first day , 1,000 μg/day on the nine following days ) had no obvious toxicity but did not improve the clinical outcome in septic shock patients . Trial Registration = NCT00207844 BACKGROUND After major burns , patients can develop nutritional deficiencies including trace element ( TE ) deficiencies .  Various complications , such as infections and delayed wound healing , influence the clinical course of such patients . OBJECTIVES We aim ed to investigate the effects of large , intravenous doses of TE supplements on circulating and cutaneous TE tissue concentrations , on antioxidant status , and on clinical outcome after major burns . DESIGN This was a prospect i ve , r and omized , placebo-controlled trial in 21 patients aged 35 + /- 11 y ( x + /- SD ) with burns on 45 + /- 21 % of their body surface area .  Intravenous copper , selenium , and zinc ( TE group ) or vehicle ( V group ) was given with a saline solution for 14 - 21 d. Blood and urine sample s were collected until day 20 , and skin biopsy specimens were collected on days 3 , 10 , and 20 . RESULTS The age of the patients and the severity of their burns did not differ significantly between the groups . Plasma TE concentrations were significantly higher in the TE group . In burned areas , skin contents of both selenium ( P=0.05 ) and zinc ( P=0.04 ) increased significantly by day 20 . Plasma and tissue antioxidant status was improved by supplementation . The number of infections in the first 30 d was significantly lower in the TE group ( P=0.015 ) , with a median number of 2 versus 4 infections per patient in the TE and V groups , respectively , as a result of a reduction in pulmonary infections ( P=0.03 ) . Wound healing was improved in the TE group , with lower requirements for regrafting ( P=0.02 ) . CONCLUSIONS TE supplementation was associated with higher circulating plasma and skin tissue contents of selenium and zinc and improved antioxidant status . These changes were associated with improved clinical outcome , including fewer pulmonary infections and better wound healing Infections remain the leading cause of death after major burns . Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury . In a previous nonr and omized study , trace element supplementation was associated with increased leukocyte counts and shortened hospital stays . This r and omized , placebo-controlled trial studied clinical and immune effects of trace element supplements .  Twenty patients , aged 40 + /- 16 y ( mean + /- SD ) , burned on 48 + /- 17 % of their body surfaces , were studied for 30 d after injury . They consumed either st and ard trace element intakes plus supplements ( 40.4 micromol Cu , 2.9 micromol Se , and 406 micromol Zn ; group TE ) or st and ard trace element intakes plus placebo ( 20 micromol Cu , 0.4 micromol Se , and 100 micromol Zn ; group C ) for 8 d. Demographic data were similar for both groups .  Mean plasma copper and zinc concentrations were below normal until days 20 and 15 , respectively ( NS ) . Plasma selenium remained normal for group TE but decreased for group C ( P < 0.05 on days 1 and 5 ) . Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts . Proliferation to mitogens was depressed compared with healthy control subjects ( NS ) . The number of infections per patient was significantly ( P < 0.05 ) lower in group TE ( 1.9 + /- 0.9 ) than in group C ( 3.1 + /- 1.1 ) because of fewer pulmonary infections . Early trace element supplementation appears beneficial after major burns ; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size Malonic dialdehyde as an indirect marker of the lipid peroxidation was found increased in the acute pancreatitis compared with persons of the same age and sex . Its concentrations inversely correlated to those of the serum calcium during the course of the disease and additionally they proved to be indicator of the prognosis . Postulating that the acute pancreatitis must be a " free radical disease " , in a r and omized clinical study the adjuvant therapy of the acute necrotizing pancreatitis ( n = 8) with sodium selenite was carried out in a daily dose of 500 micrograms . The lethality of the control group was 89 % ( 8 out of altogether 9 patients ) , no patient died in the therapy group . By the selenium therapy within 24 hours a normalization of the serum calcium and a decrease of the increased MDA-values could be achieved . It was concluded that by selenium increased activities of the phospholipid-hydroperoxide-glutathione peroxidase were induced , by means of which a peroxidation protection of membrane fatty acids , an inhibition of the activity of phospholipase A2 and an interruption of the arachidonic acid cascade must have been reached Objective To determine the effectiveness of early , routine antioxidant supplementation using & agr;-tocopherol and ascorbic acid in reducing the rate of pulmonary morbidity and organ dysfunction in critically ill surgical patients . Summary Background Data Oxidative stress has been associated with the development of the acute respiratory distress syndrome ( ARDS ) and organ failure through direct tissue injury and activation of genes integral to the inflammatory response . In addition , depletion of endogenous antioxidants has been associated with an increased risk of nosocomial infections . The authors postulated that antioxidant supplementation in critically ill surgical patients may reduce the incidence of ARDS , pneumonia , and organ dysfunction . Methods This r and omized , prospect i ve study was conducted to compare outcomes in patients receiving antioxidant supplementation ( & agr;-tocopherol and ascorbate ) versus those receiving st and ard care .  The primary endpoint for analysis was pulmonary morbidity ( a composite measure of ARDS and nosocomial pneumonia ) . Secondary endpoints included the development of multiple organ failure , duration of mechanical ventilation , length of ICU stay , and mortality . Results Five hundred ninety-five patients were enrolled and analyzed , 91 % of whom were victims of trauma . The relative risk of pulmonary morbidity was 0.81 ( 95 % confidence interval 0.60–1.1 ) in patients receiving antioxidant supplementation .  Multiple organ failure was significantly less likely to occur in patients receiving antioxidants  than in patients receiving st and ard care  , with a relative risk of 0.43 ( 95 % confidence interval 0.19–0.96 ) . Patients r and omized to antioxidant supplementation also had a shorter duration of mechanical ventilation and length of ICU stay . Conclusions The early administration of antioxidant supplementation using & agr;-tocopherol and ascorbic acid reduces the incidence of organ failure and shortens ICU length of stay in this cohort of critically ill surgical patients Sixty-eight patients were entered into a r and omized , prospect i ve , double-blinded controlled trial of supplemental zinc versus st and ard zinc therapy to study the effects of zinc supplementation on neurologic recovery and nutritional/metabolic status after severe closed head injury . One month after injury , the mortality rates in the  st and ard zinc group and the zinc-supplemented group were 26 and 12 % , respectively . Glasgow Coma Scale ( GCS ) scores of the zinc-supplemented group exceeded the adjusted mean GCS score of the st and ard group at day 28 ( p = 0.03 ) . Mean motor GCS score levels of the zinc-supplemented group were significantly higher on days 15 and 21 than those of the control group ( p = 0.005 , p = 0.02 ) . This trend continued on day 28 of the study ( p = 0.09 ) . The groups did not differ in serum zinc concentration , weight , energy expenditure , or total urinary nitrogen excretion after hospital admission . Mean 24-h urine zinc levels were significantly higher in the zinc-supplemented group at days 2 ( p = 0.0001 ) and 10 ( p = 0.01 ) after injury . Mean serum prealbumin concentrations were significantly higher in the zinc-supplemented group ( p = 0.003 ) at 3 weeks after injury . A similar pattern was found for mean serum retinol binding protein level ( p = 0.01 ) . A significantly larger number of patients in the st and ard zinc group had craniotomies for evacuation of hematoma ; thus a bias may have been present . The results of this study indicate that zinc supplementation during the immediate postinjury period is associated with improved rate of neurologic recovery and visceral protein concentrations for patients with severe closed head injury BACKGROUND Supplementation with glutamine and antioxidants may be associated with an improvement in clinical outcomes , but the optimal dose of these substrates is unknown . The purpose of this study was to determine the safety of high doses of glutamine combined with antioxidants in critically ill patients . METHODS We conducted a single-center , open-label , dose-escalating clinical trial . Mechanically ventilated adult patients with clinical evidence of hypoperfusion were sequentially enrolled to 1 of 5 groups . Group 1 ( n = 30 ) : no supplementation ; group 2 ( n = 7 ) : 0.35 g/kg/d of glutamine IV ; group 3 ( n = 7 ) : same as group 2 plus 15 g/d of glutamine and 150 microg of selenium enterally ; group 4 ( n = 7 ) : same as group 2 plus 30 g/d of glutamine and 300 microg of selenium enterally ; and group 5 ( n = 7 ) : same as group 4 plus an additional 500 microg of selenium IV . After enrollment , nutrients were started as soon as possible . All patients were fed enterally according to clinical practice guidelines . RESULTS The primary outcomes for this study were change in sequential organ function assessment ( SOFA ) score and safety parameters . Secondary outcomes included whole blood glutathione ( GSH ) , thiobarbituric acid reactive substances ( TBARS ) , and blood cells ' mitochondrial DNA/nuclear DNA ratio ( RATIO ) . There were no adverse events attributable to the study nutrients , and the maximum and Delta SOFA did not differ across groups . In group 2 , a significant decrease in GSH levels was observed ( p = .03 ) . With subsequent groups , the slopes straighten out and the p values are no longer significant , suggesting a greater preservation of GSH levels with escalating doses . In group 2 , the slope of the line representing TBARS was horizontal . With subsequent groups , the slopes decrease , and by group 5 , this decrease reaches statistical significance ( p = .03 ) , suggesting a greater reduction in oxidative stress with the higher doses in group 5 . The difference in slopes across all groups describing the mitochondrial RATIO is statistically significant ( p = .001 ) , again suggesting that , with higher doses , there is increased mitochondrial function . CONCLUSIONS The doses of glutamine and antioxidants tested in this study seem to be safe and may have positive effects on some mechanistic endpoints . A larger trial will be necessary to confirm their therapeutic effects OBJECTIVE To determine the effect of selenium replacement on morbidity and mortality in patients with systemic inflammatory response syndrome ( SIRS ) . DESIGN Controlled , r and omized prospect i ve open-label pilot study comparing patients with and without selenium replacement .  SETTING Intensive care unit of a university hospital for internal medicine . PATIENTS Forty-two patients with 
    Output:
    
Micronutrient supplementation was not associated with a decrease in infectious complications , length of intensive care unit , or length of hospital stay .
The secondary outcomes confirmed that timing , duration , and dosing appear to be key factors to ensure optimal clinical benefit .
This review does suggest a potential benefit of micronutrient supplementation in critically ill adults by possibly being associated with a decrease in mortality