***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: Objective : To determine if ketoconazole , a thromboxane A2 synthetase inhibitor , given within the first 24 hrs after diagnosis and arrival in the intensive care unit ( ICU ) would decrease the frequency of adult respiratory distress syndrome in the septic patient population . Design : Prospect i ve , r and omized , double-blind , placeocontrolled study . Setting : Twelve-bed , surgical ICU in a university-affiliated hospital . Patients : Fifty-four consecutive patients admitted to the surgical ICU with the diagnosis of sepsis composed the study sample . Sepsis was defined as including two or more of the following signs in a patient with a systolic blood pressure of < 80 mm Hg or a systemic vascular resistance of < 800 dyne-sec/cm5 : a ) temperature ≥39 ° C or ≤35 ° C ; b ) white blood cell count of > 12,000 leukocytes , or ≤4000 leukocytes/μL , or ≥20 % immature cells ; c ) positive blood culture ; d ) known or strongly suspected source of infection from which a known pathogen was cultured . Interventions : Patients were r and omized to receive either ketoconazole ( 400 mg ) or placebo in a double-blind fashion as early as possible and in < 24 hrs after surgical ICU admission or after the diagnosis of sepsis was established . Measurements and Main Results : Adult respiratory distress syndrome ( ARDS ) was diagnosed if the following criteria were met : a ) intrapulmonary shunt of > 20 % , or a PaO2/Fio2 ratio of < 150 requiring ventilatory support for > 48 hrs ; b ) pulmonary artery occlusion pressure of < 18 nun Hg and no clinical signs of heart failure ; and c ) diffuse infiltrates on chest radiograph . Treatment result ed in significant ( p = .002 ) reduction in the frequency of ARDS compared with the placebo group , 64 % vs. 15 % in the ketoconazole treated group . The mortality rate was also reduced from 39 % in the placebo group to 15 % in the ketoconazole group ( p = .05 ) . A statistically significant reduction in ventilator and ICU days was not achieved . Conclusions : Ketoconazole ( 400 mg through the gastrointestinal tract ) given early in the septic course may prevent ARDS and decrease the mortality rate in high-risk , septic patients . ( Crit Care Med 1993 ; 21:1635–1642 Objective To determine whether caloric intake is associated with risk of nosocomial bloodstream infection in critically ill medical patients . Design Prospect i ve cohort study . Setting Urban , academic medical intensive care unit . Patients Patients were 138 adult patients who did not take food by mouth for ≥96 hrs after medical intensive care unit admission . Measurements Daily caloric intake was recorded for each patient . Participants subsequently were grouped into one of four categories of caloric intake : < 25 % , 25–49 % , 50–74 % , and ≥75 % of average daily recommended calories based on the American College of Chest Physicians guidelines . Simplified Acute Physiology Score II and serum albumin were measured on medical intensive care unit admission .  Serum glucose ( average value and maximum value each day ) and route of feeding ( enteral , parenteral , or both ) were collected daily . Nosocomial bloodstream infections were identified by infection control surveillance methods . Main Results The overall mean ( ±sd ) daily caloric intake for all study participants was 49.4 ± 29.3 % of American College of Chest Physicians guidelines . Nosocomial bloodstream infection occurred in 31 ( 22.4 % ) participants . Bivariate Cox analysis revealed that receiving ≥25 % of recommended calories compared with < 25 % was associated with significantly lower risk of bloodstream infection ( relative hazard , 0.24 ; 95 % confidence interval , 0.10–0.60 ) . Simplified Acute Physiology Score II also was associated with risk of nosocomial bloodstream infection ( relative hazard , 1.27 ; 95 % confidence interval , 1.01–1.60 ) . Average daily serum glucose , admission serum albumin , time to initiating nutritional support , and route of nutrition did not affect risk of bloodstream infection . After adjustment for Simplified Acute Physiology Score II in a multivariable analysis , receiving ≥25 % of recommended calories was associated with a significantly lower risk of bloodstream infection ( relative hazard , 0.27 ; 95 % confidence interval , 0.11–0.68 ) . Conclusions In the context of reducing risk of nosocomial bloodstream infections , failing to provide ≥25 % of the recommended calories may be harmful . Higher caloric goals may be necessary to achieve other clinical ly important outcomes We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus . 55 Sprague-Dawley rats were r and omized to either intravenous saline or lipopolysaccharide ( LPS ) . After 50 min of spontaneous respiration , the lungs were excised and r and omized to 2 h of ventilation with one of four strategies : ( a ) control ( C ) , tidal volume ( Vt ) = 7 cc/kg , positive end expiratory pressure ( PEEP ) = 3 cm H2O ; ( b ) moderate volume , high PEEP ( MVHP ) , Vt = 15 cc/kg ; PEEP = 10 cm H2O ; ( c ) moderate volume , zero PEEP ( MVZP ) , Vt = 15 cc/kg , PEEP = 0 ; or ( d ) high volume , zero PEEP ( HVZP ) , Vt = 40 cc/kg , PEEP = 0 . Ventilation with zero PEEP ( MVZP , HVZP ) result ed in significant reductions in lung compliance . Lung lavage levels of TNFalpha , IL-1beta , IL-6 , IL-10 , MIP-2 , and IFNgamma were measured by ELISA . Zero PEEP in combination with high volume ventilation ( HVZP ) had a synergistic effect on cytokine levels ( e.g. , 56-fold increase of TNFalpha versus controls ) . Identical end inspiratory lung distention with PEEP ( MVHP ) result ed in only a three-fold increase in TNFalpha , whereas MVZP produced a six-fold increase in lavage TNFalpha . Northern blot analysis revealed a similar pattern ( C , MVHP < MVZP < HVZP ) for induction of c-fos mRNA . These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung , and thus may play a role in initiating or propagating a local , and possibly systemic inflammatory response OBJECTIVES Recent studies in animal models of sepsis-induced acute respiratory distress syndrome ( ARDS ) have shown that a low-carbohydrate , high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid ( EPA ; fish oil ) , gamma-linolenic acid ( GLA ; borage oil ) ( EPA+GLA ) , and antioxidants improves lung microvascular permeability , oxygenation , and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation . These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS . DESIGN Prospect i ve , multicentered , double-blind , r and omized controlled trial . SETTING Intensive care units of five academic and teaching hospitals in the United States . PATIENTS We enrolled 146 patients with ARDS ( as defined by the American-European Consensus Conference ) caused by sepsis/pneumonia , trauma , or aspiration injury in the study . INTERVENTIONS Patients meeting entry criteria were r and omized and continuously tube-fed either EPA+GLA or an isonitrogenous , isocaloric st and ard diet at a minimum caloric delivery of 75 % of basal energy expenditure x 1.3 for at least 4 - 7 days . MEASUREMENTS AND MAIN RESULTS Arterial blood gases were measured , and ventilator setting s were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2 , a measure of gas exchange . Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points . Clinical outcomes were recorded . Baseline characteristics of 98 evaluable patients revealed that key demographic , physiologic , and ventilatory variables were similar at entry between both groups . Multiple bronchoalveolar lavages revealed significant decreases ( approximately 2.5-fold ) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet . Significant improvements in oxygenation ( PaO2/FIO2 ) from baseline to study days 4 and 7 with lower ventilation variables ( FIO2 , positive end-expiratory pressure , and minute ventilation ) occurred in patients fed EPA+GLA compared with controls . Patients fed EPA+GLA required significantly fewer days of ventilatory support ( 11 vs. 16.3 days ; p = .011 ) , and had a decreased length of stay in the intensive care unit ( 12.8 vs. 17.5 days ; p = .016 ) compared with controls . Only four of 51 ( 8 % ) patients fed EPA+GLA vs. 13 of 47 ( 28 % ) control patients developed a new organ failure during the study ( p = .015 ) . CONCLUSIONS The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment , gas exchange , requirement for mechanical ventilation , length of intensive care unit stay , and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS Objective : It has been shown in a two-center study that high positive end-expiratory pressure ( PEEP ) and low tidal volume ( LTV ) improved outcome in ARDS . However , that study involved patients with underlying diseases unique to the study area , was conducted at only two centers , and enrolled a small number of patients . We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system ( Pflex ) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome ( ARDS ) . Design : R and omized , controlled clinical trial . Setting : Network of eight Spanish multidisciplinary intensive care units ( ICUs ) under the acronym of ARIES ( Acute Respiratory Insufficiency : España Study ) . Patients : All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study . If 24 hrs after meeting ARDS criteria , the Pao2/Fio2 remained ≤200 mm Hg on st and ard ventilator setting s , patients were r and omized into two groups : control and Pflex/LTV . Interventions : In the control group , tidal volume was 9–11 mL/kg of predicted body weight ( PBW ) and PEEP ≥5 cm H2O . In the Pflex/LTV group , tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O . In both groups , Fio2 was set to maintain arterial oxygen saturation > 90 % and Pao2 70–100 mm Hg , and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg . Measurements and Main Results : The study was stopped early based on an efficacy stopping rule as described in the methods . Of 103 patients who were enrolled ( 50 control and 53 Pflex ) , eight patients ( five in control , three in Pflex ) were excluded from the final evaluation because the r and om group assignment was not performed in one center according to protocol . Main outcome measures were ICU and hospital mortality , ventilator-free days , and nonpulmonary organ dysfunction . ICU mortality ( 24 of 45 [ 53.3 % ] vs. 16 of 50 [ 32 % ] , p = .040 ) , hospital mortality ( 25 of 45 [ 55.5 % ] vs. 17 of 50 [ 34 % ] , p = .041 )  , and ventilator-free days at day 28 ( 6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV , p = .008 ) all favored Pflex/LTV . The mean difference in the number of additional organ failures postr and omization was higher in the control group ( p < .001 ) . Conclusions : A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS OBJECTIVE To determine whether the implementation of a nutritional management protocol in the ICU leads to the increased use of enteral nutrition , earlier feeding , and improved clinical outcomes in patients . DESIGN Prospect i ve evaluation of critically ill patients before and after the introduction of an 
    Output:
    
Grasso S , Stripoli T , De Michele M , et al. ARDSnet ventilatory protocol and alveolar hyperinflation : role of positive endexpiratory pressure .