human
***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 Optimal fluid management in patients with acute lung injury is unknown . Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion . METHODS In a r and omized study , we compared a conservative and a liberal strategy of fluid management using explicit protocol s applied for seven days in 1000 patients with acute lung injury . The primary end point was death at 60 days . Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology . RESULTS The rate of death at 60 days was 25.5 percent in the conservative- strategy group and 28.4 percent in the liberal- strategy group ( P=0.30 ; 95 percent confidence interval for the difference , -2.6 to 8.4 percent ) . The mean ( + /-SE ) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative- strategy group and 6992+/-502 ml in the liberal- strategy group ( P<0.001 ) . As compared with the liberal strategy , the conservative strategy improved the oxygenation index ( [ mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen]x100 ) and the lung injury score and increased the number of ventilator-free days ( 14.6+/-0.5 vs. 12.1+/-0.5 , P<0.001 ) and days not spent in the intensive care unit ( 13.4+/-0.4 vs. 11.2+/-0.4 , P<0.001 ) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days ( 10 percent vs. 14 percent , P=0.06 ) . CONCLUSIONS Although there was no significant difference in the primary outcome of 60-day mortality , the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures . These results support the use of a conservative strategy of fluid management in patients with acute lung injury . ( Clinical Trials.gov number , NCT00281268 [ Clinical Trials.gov ] . ) Nuclear factor-kappaB ( NF-kappaB ) and glucocorticoid receptor-alpha ( GR-alpha ) have diametrically opposed functions in regulating inflammation . We investigated whether unresolving acute respiratory distress syndrome ( ARDS ) is associated with systemic inflammation- induced glucocorticoid resistance and whether prolonged methylprednisolone administration accelerates the suppression of systemic inflammatory indices and normalizes the sensitivity of the immune system to glucocorticoids . Patients enrolled into a r and omized trial evaluating prolonged methylprednisolone administration in unresolving ARDS had serial plasma sample s collected before and after r and omization . In the plasma , we measured the concentrations of tumor necrosis factor-alpha ( TNF-alpha ) , interleukins ( IL ) IL-1beta and IL-6 , adrenocorticotropic hormone ( ACTH ) , and cortisol . The ability of patient plasma to influence the NF-kappaB and GR-signal transduction systems of normal peripheral blood leukocytes ( PBL ) was examined . Patients treated with methylprednisolone had progressive and sustained reductions of TNF-alpha , IL-1beta , IL-6 , ACTH , and cortisol concentrations over time . Normal PBL exposed to plasma sample s collected during methylprednisolone exhibited significant progressive increases in all aspects of GR-mediated activity and significant reductions in NF-kappaB DNA-binding and transcription of TNF-alpha and IL-1beta . These findings provide support for the presence of endogenous glucocorticoid inadequacy in the control of inflammation and systemic inflammation-induced peripheral glucocorticoid resistance in ARDS . Prolonged methylprednisolone administration accelerated the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in ARDS Objective To determine whether ICU-acquired paresis ( ICUAP ) is an independent risk factor of prolonged weaning . Design Second study of a prospect i ve cohort of 95 patients who were enrolled in an incidence and risk factor study of ICUAP . Setting Three medical and two surgical ICUs in four hospitals . Patients and participants Ninety-five patients without pre-existing neuromuscular disease recovering from the acute phase of critical illness after ≥7 days of mechanical ventilation . Interventions None . Measurements and results Duration of weaning from mechanical ventilation  was defined as the duration of mechanical ventilation between awakening ( day 1 ) and successful weaning . Muscle strength was evaluated at day 7 after awakening using the Medical Research Council ( MRC ) score . Patients with an MRC < 48 were considered to have ICUAP . Among the 95 patients ( mean age 62.0±15.3 years , SAPS 2 on admission 48.7±17.4 ) who regained satisfactory awakening after 7 or more days of mechanical ventilation , 67 ( 70.5 % ) were hospitalized in a medical ICU and 28 ( 29.5 % ) in a surgical ICU . Median duration ( 25th–75th percentiles ) of weaning was longer in patients with ICUAP than in those without ICUAP : 6 days ( 1–22 days ) vs 3 days ( 1–7 days ) ; p=0.01 ; log-rank analysis . In multivariate analysis , the two independent predictors of prolonged weaning were ICUAP [ hazard ratio ( HR ) : 2.4 ; 95 % confidence interval ( CI ) : 1.4–4.2 ] and chronic obstructive pulmonary disease ( HR : 2.7 ; 95 % CI : 1.6–4.5 ) Conclusions ICU-acquired paresis is an independent predictor of prolonged weaning . Prevention of ICU-acquired neuromuscular abnormalities in patients recovering from severe acute illness should result in shorter weaning duration BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use BACKGROUND The acute respiratory distress syndrome ( ARDS ) that develops after thoracic surgery is usually lethal . The use of corticosteroids to treat ARDS has been the subject of great controversy . METHODS Therefore we compared conventional therapy with early low-dose steroid therapy in the treatment of postoperative ARDS . Methylprednisolone was given daily as an intravenous push every 6 hours and was changed to a single oral dose or discontinued , with a loading dose of 2 mg/kg followed by 2 mg/kg per day . RESULTS Over 2.5 years , 523 major thoracic operations were performed with postoperative ARDS developing in 20 patients ( 3.8 % ) , of which 8 were treated with conventional therapy  and 12 with early low-dose steroid therapy . Early low-dose steroid therapy significantly reduced postoperative mortality , with 7 patients ( 58.3 % ) recovering without mechanical ventilation . CONCLUSIONS We believe this is the first clinical study of low-dose methylprednisolone at an early phase of postoperative ARDS . The beneficial effects of the use of early low-dose steroids in ARDS are consistent with the hypothesis that fibroproliferation is an early response to lung injury , which is inhibited by early low-dose steroid therapy without disturbing operative wound healing BACKGROUND Persistent acute respiratory distress syndrome ( ARDS ) is characterized by excessive fibroproliferation , ongoing inflammation , prolonged mechanical ventilation , and a substantial risk of death . Because previous reports suggested that corticosteroids may improve survival , we performed a multicenter , r and omized controlled trial of corticosteroids in patients with persistent ARDS . METHODS We r and omly assigned 180 patients with ARDS of at least seven days ' duration to receive either methylprednisolone or placebo in a double-blind fashion . The primary end point was mortality at 60 days . Secondary end points included the number of ventilator-free days and organ-failure-free days , biochemical markers of inflammation and fibroproliferation , and infectious complications . RESULTS At 60 days , the hospital mortality rate was 28.6 percent in the placebo group ( 95 percent confidence interval , 20.3 to 38.6 percent ) and 29.2 percent in the methylprednisolone group ( 95 percent confidence interval , 20.8 to 39.4 percent ; P=1.0 ) ; at 180 days , the rates were 31.9 percent ( 95 percent confidence interval , 23.2 to 42.0 percent ) and 31.5 percent ( 95 percent confidence interval , 22.8 to 41.7 percent ; P=1.0 ) , respectively . Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS . Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation , respiratory-system compliance , and blood pressure with fewer days of vasopressor therapy . As compared with placebo , methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness . CONCLUSIONS These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology . In addition , starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death . ( Clinical Trials.gov number , NCT00295269 . ) Within the last few years , increasing evidence of relative adrenal insufficiency in septic shock evoked a re assessment of hydrocortisone therapy . To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation , 40 patients with septic shock were r and omized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 ( n = 20 ) or placebo ( n = 20 ) , followed by the opposite medication until Day 6 . Hydrocortisone infusion induced an increase of mean arterial pressure , systemic vascular resistance , and a decline of heart rate , cardiac index , and norepinephrine requirement . A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support . The inflammatory response ( interleukin-6 and interleukin-8 ) , endothelial ( soluble E-selectin ) and neutrophil activation ( expression of CD11b , CD64 ) , and antiinflammatory response ( soluble tumor necrosis factor receptors I and II and interleukin-10 ) were attenuated . In peripheral blood monocytes , human leukocyte antigen-DR expression was only slightly depressed , whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased . Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects . In conclusion , hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression We hypothesize that hydrocortisone infusion in severe community-ac 
    Output:
    
agent
***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 Optimal fluid management in patients with acute lung injury is unknown . Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion . METHODS In a r and omized study , we compared a conservative and a liberal strategy of fluid management using explicit protocol s applied for seven days in 1000 patients with acute lung injury . The primary end point was death at 60 days . Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology . RESULTS The rate of death at 60 days was 25.5 percent in the conservative- strategy group and 28.4 percent in the liberal- strategy group ( P=0.30 ; 95 percent confidence interval for the difference , -2.6 to 8.4 percent ) . The mean ( + /-SE ) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative- strategy group and 6992+/-502 ml in the liberal- strategy group ( P<0.001 ) . As compared with the liberal strategy , the conservative strategy improved the oxygenation index ( [ mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen]x100 ) and the lung injury score and increased the number of ventilator-free days ( 14.6+/-0.5 vs. 12.1+/-0.5 , P<0.001 ) and days not spent in the intensive care unit ( 13.4+/-0.4 vs. 11.2+/-0.4 , P<0.001 ) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days ( 10 percent vs. 14 percent , P=0.06 ) . CONCLUSIONS Although there was no significant difference in the primary outcome of 60-day mortality , the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures . These results support the use of a conservative strategy of fluid management in patients with acute lung injury . ( Clinical Trials.gov number , NCT00281268 [ Clinical Trials.gov ] . ) Nuclear factor-kappaB ( NF-kappaB ) and glucocorticoid receptor-alpha ( GR-alpha ) have diametrically opposed functions in regulating inflammation . We investigated whether unresolving acute respiratory distress syndrome ( ARDS ) is associated with systemic inflammation- induced glucocorticoid resistance and whether prolonged methylprednisolone administration accelerates the suppression of systemic inflammatory indices and normalizes the sensitivity of the immune system to glucocorticoids . Patients enrolled into a r and omized trial evaluating prolonged methylprednisolone administration in unresolving ARDS had serial plasma sample s collected before and after r and omization . In the plasma , we measured the concentrations of tumor necrosis factor-alpha ( TNF-alpha ) , interleukins ( IL ) IL-1beta and IL-6 , adrenocorticotropic hormone ( ACTH ) , and cortisol . The ability of patient plasma to influence the NF-kappaB and GR-signal transduction systems of normal peripheral blood leukocytes ( PBL ) was examined . Patients treated with methylprednisolone had progressive and sustained reductions of TNF-alpha , IL-1beta , IL-6 , ACTH , and cortisol concentrations over time . Normal PBL exposed to plasma sample s collected during methylprednisolone exhibited significant progressive increases in all aspects of GR-mediated activity and significant reductions in NF-kappaB DNA-binding and transcription of TNF-alpha and IL-1beta . These findings provide support for the presence of endogenous glucocorticoid inadequacy in the control of inflammation and systemic inflammation-induced peripheral glucocorticoid resistance in ARDS . Prolonged methylprednisolone administration accelerated the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in ARDS Objective To determine whether ICU-acquired paresis ( ICUAP ) is an independent risk factor of prolonged weaning . Design Second study of a prospect i ve cohort of 95 patients who were enrolled in an incidence and risk factor study of ICUAP . Setting Three medical and two surgical ICUs in four hospitals . Patients and participants Ninety-five patients without pre-existing neuromuscular disease recovering from the acute phase of critical illness after ≥7 days of mechanical ventilation . Interventions None . Measurements and results Duration of weaning from mechanical ventilation  was defined as the duration of mechanical ventilation between awakening ( day 1 ) and successful weaning . Muscle strength was evaluated at day 7 after awakening using the Medical Research Council ( MRC ) score . Patients with an MRC < 48 were considered to have ICUAP . Among the 95 patients ( mean age 62.0±15.3 years , SAPS 2 on admission 48.7±17.4 ) who regained satisfactory awakening after 7 or more days of mechanical ventilation , 67 ( 70.5 % ) were hospitalized in a medical ICU and 28 ( 29.5 % ) in a surgical ICU . Median duration ( 25th–75th percentiles ) of weaning was longer in patients with ICUAP than in those without ICUAP : 6 days ( 1–22 days ) vs 3 days ( 1–7 days ) ; p=0.01 ; log-rank analysis . In multivariate analysis , the two independent predictors of prolonged weaning were ICUAP [ hazard ratio ( HR ) : 2.4 ; 95 % confidence interval ( CI ) : 1.4–4.2 ] and chronic obstructive pulmonary disease ( HR : 2.7 ; 95 % CI : 1.6–4.5 ) Conclusions ICU-acquired paresis is an independent predictor of prolonged weaning . Prevention of ICU-acquired neuromuscular abnormalities in patients recovering from severe acute illness should result in shorter weaning duration BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use BACKGROUND The acute respiratory distress syndrome ( ARDS ) that develops after thoracic surgery is usually lethal . The use of corticosteroids to treat ARDS has been the subject of great controversy . METHODS Therefore we compared conventional therapy with early low-dose steroid therapy in the treatment of postoperative ARDS . Methylprednisolone was given daily as an intravenous push every 6 hours and was changed to a single oral dose or discontinued , with a loading dose of 2 mg/kg followed by 2 mg/kg per day . RESULTS Over 2.5 years , 523 major thoracic operations were performed with postoperative ARDS developing in 20 patients ( 3.8 % ) , of which 8 were treated with conventional therapy  and 12 with early low-dose steroid therapy . Early low-dose steroid therapy significantly reduced postoperative mortality , with 7 patients ( 58.3 % ) recovering without mechanical ventilation . CONCLUSIONS We believe this is the first clinical study of low-dose methylprednisolone at an early phase of postoperative ARDS . The beneficial effects of the use of early low-dose steroids in ARDS are consistent with the hypothesis that fibroproliferation is an early response to lung injury , which is inhibited by early low-dose steroid therapy without disturbing operative wound healing BACKGROUND Persistent acute respiratory distress syndrome ( ARDS ) is characterized by excessive fibroproliferation , ongoing inflammation , prolonged mechanical ventilation , and a substantial risk of death . Because previous reports suggested that corticosteroids may improve survival , we performed a multicenter , r and omized controlled trial of corticosteroids in patients with persistent ARDS . METHODS We r and omly assigned 180 patients with ARDS of at least seven days ' duration to receive either methylprednisolone or placebo in a double-blind fashion . The primary end point was mortality at 60 days . Secondary end points included the number of ventilator-free days and organ-failure-free days , biochemical markers of inflammation and fibroproliferation , and infectious complications . RESULTS At 60 days , the hospital mortality rate was 28.6 percent in the placebo group ( 95 percent confidence interval , 20.3 to 38.6 percent ) and 29.2 percent in the methylprednisolone group ( 95 percent confidence interval , 20.8 to 39.4 percent ; P=1.0 ) ; at 180 days , the rates were 31.9 percent ( 95 percent confidence interval , 23.2 to 42.0 percent ) and 31.5 percent ( 95 percent confidence interval , 22.8 to 41.7 percent ; P=1.0 ) , respectively . Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS . Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation , respiratory-system compliance , and blood pressure with fewer days of vasopressor therapy . As compared with placebo , methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness . CONCLUSIONS These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology . In addition , starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death . ( Clinical Trials.gov number , NCT00295269 . ) Within the last few years , increasing evidence of relative adrenal insufficiency in septic shock evoked a re assessment of hydrocortisone therapy . To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation , 40 patients with septic shock were r and omized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 ( n = 20 ) or placebo ( n = 20 ) , followed by the opposite medication until Day 6 . Hydrocortisone infusion induced an increase of mean arterial pressure , systemic vascular resistance , and a decline of heart rate , cardiac index , and norepinephrine requirement . A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support . The inflammatory response ( interleukin-6 and interleukin-8 ) , endothelial ( soluble E-selectin ) and neutrophil activation ( expression of CD11b , CD64 ) , and antiinflammatory response ( soluble tumor necrosis factor receptors I and II and interleukin-10 ) were attenuated . In peripheral blood monocytes , human leukocyte antigen-DR expression was only slightly depressed , whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased . Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects . In conclusion , hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression We hypothesize that hydrocortisone infusion in severe community-ac 
    Output:
    