***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 
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    Input: RATIONALE Critical illness survivors often experience permanent functional disability due to intensive care unit (ICU)-acquired weakness . The mechanisms responsible for long-term weakness persistence versus resolution are unknown . OBJECTIVES To delineate cellular mechanisms underlying long-term weakness persistence in ICU survivors . METHODS We conducted a nested , prospect i ve study of critically ill patients mechanically ventilated for 7 days or longer . The patients were recruited from the RECOVER program  and serially assessed over 6 months after ICU discharge . Twenty-seven of 82 patients consented to participate ; 15 and 11 patients were assessed at 7 days and 6 months after ICU discharge , respectively . MEASUREMENTS AND MAIN RESULTS We assessed motor functional capacity , quadriceps size , strength , and voluntary contractile capacity and performed electromyography , nerve conduction studies , and vastus lateralis biopsies  for histologic , cellular , and molecular analyses . Strength and quadriceps cross-sectional areas were decreased 7 days after ICU discharge . Weakness persisted to 6 months and correlated with decreased function . Quadriceps atrophy resolved in 27 % patients at 6 months . Muscle mass reconstitution did not correlate with resolution of weakness , owing to persistent impaired voluntary contractile capacity . Compared with Day 7 , increased ubiquitin-proteasome system-mediated muscle proteolysis , inflammation , and decreased mitochondrial content all normalized at 6 months . Autophagy markers were normal at 6 months . Patients with sustained atrophy had decreased muscle progenitor ( satellite ) cell content . CONCLUSIONS Long-term weakness in ICU survivors results from heterogeneous muscle pathophysiology with variable combinations of muscle atrophy and impaired contractile capacity . These findings are not explained by ongoing muscle proteolysis , inflammation , or diminished mitochondrial content . Sustained muscle atrophy is associated with decreased satellite cell content and compromised muscle regrowth , suggesting impaired regenerative capacity RATIONALE Intensive care unit (ICU)-acquired weakness is a frequent complication of critical illness . It is unclear whether it is a marker or mediator of poor outcomes . OBJECTIVES To determine acute outcomes , 1-year mortality , and costs of ICU-acquired weakness among long-stay ( ≥8 d ) ICU patients and to assess the impact of recovery of weakness at ICU discharge . METHODS Data were prospect ively collected during a r and omized controlled trial . Impact of weakness on outcomes and costs was analyzed with a one-to-one propensity-score-matching for baseline characteristics , illness severity , and risk factor exposure before assessment . Among weak patients , impact of persistent weakness at ICU discharge on risk of death after 1 year was examined with multivariable Cox proportional hazards analysis . MEASUREMENTS AND MAIN RESULTS A total of 78.6 % were admitted to the surgical ICU ; 227 of 415 ( 55 % ) long-stay assessable ICU patients were weak ; 122 weak patients were matched to 122 not-weak patients . As compared with matched not-weak patients , weak patients had a lower likelihood for live weaning from mechanical ventilation ( hazard ratio [ HR ] , 0.709 [ 0.549 - 0.888 ] ; P = 0.009 ) , live ICU ( HR , 0.698 [ 0.553 - 0.861 ] ; P = 0.008 ) and hospital discharge ( HR , 0.680 [ 0.514 - 0.871 ] ; P = 0.007 ) . In-hospital costs per patient ( + 30.5 % , + 5,443 Euro per patient ; P = 0.04 ) and 1-year mortality ( 30.6 % vs. 17.2 % ; P = 0.015 ) were also higher . The 105 of 227 ( 46 % ) weak patients not matchable to not-weak patients had even worse prognosis and higher costs . The 1-year risk of death was further increased if weakness persisted and was more severe as compared with recovery of weakness at ICU discharge ( P < 0.001 ) . CONCLUSIONS After careful matching the data suggest that ICU-acquired weakness worsens acute morbidity and increases healthcare-related costs and 1-year mortality . Persistence and severity of weakness at ICU discharge further increased 1-year mortality . Clinical trial registered with www . clinical trials.gov ( NCT 00512122 ) 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 Introduction Critical illness myopathy and /or neuropathy ( CRIMYNE ) is frequent in intensive care unit ( ICU ) patients . Although complete electrophysiological tests of peripheral nerves and muscles are essential to diagnose it , they are time-consuming , precluding extensive use in daily ICU practice . We evaluated whether a simplified electrophysiological investigation of only two nerves could be used as an alternative to complete electrophysiological tests . Methods In this prospect i ve , multi-centre study , 92 ICU patients were subjected to unilateral daily measurements of the action potential amplitude of the sural and peroneal nerves ( compound muscle action potential [ CMAP ] ) . After the first ten days , complete electrophysiological investigations were carried out weekly until ICU discharge or death . At hospital discharge , complete neurological and electrophysiological investigations were performed . Results Electrophysiological signs of CRIMYNE occurred in 28 patients ( 30.4 % , 95 % confidence interval [ CI ] 21.9 % to 40.4 % ) . A unilateral peroneal CMAP reduction of more than two st and ard deviations of normal value showed the best combination of sensitivity ( 100 % ) and specificity ( 67 % ) in diagnosing CRIMYNE . All patients developed the electrophysiological signs of CRIMYNE within 13 days of ICU admission . Median time from ICU admission to CRIMYNE was six days ( 95 % CI five to nine days ) . In 10 patients , the amplitude of the nerve action potential dropped progressively over a median of 3.0 days , and in 18 patients it dropped abruptly within 24 hours . Multi-organ failure occurred in 21 patients ( 22.8 % , 95 % CI 15.4 % to 32.4 % ) and was strongly associated with CRIMYNE ( odds ratio 4.58 , 95 % CI 1.64 to 12.81 ) . Six patients with CRIMYNE died : three in the ICU and three after ICU discharge . Hospital mortality was similar in patients with and without CRIMYNE ( 21.4 % and 17.2 % ; p = 0.771 ) . At ICU discharge , electrophysiological signs of CRIMYNE persisted in 18 ( 64.3 % ) of 28 patients . At hospital discharge , diagnoses in the 15 survivors were critical illness myopathy ( CIM ) in six cases , critical illness polyneuropathy ( CIP ) in four , combined CIP and CIM in three , and undetermined in two . Conclusion A peroneal CMAP reduction below two st and ard deviations of normal value accurately identifies patients with CRIMYNE . These should have full neurological and neurophysiological evaluations before discharge from the acute hospital Objectives : To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival . Design : Longitudinal prospect i ve cohort study over 5 years of follow-up . Setting : Thirteen ICUs in four hospitals in Baltimore , MD . Patients : One hundred fifty-six acute respiratory distress syndrome survivors . Interventions : None . Measurements and Main Results : Strength was evaluated with st and ardized manual muscle testing  using the  Medical Research Council sum score ( range , 0–60 ; higher is better ) , with post-ICU weakness defined as sum score less than 48 . Muscle strength was assessed at hospital discharge and at 3 , 6 , 12 , 24 , 36 , and 48 months after acute respiratory distress syndrome . At discharge , 38 % of patients had  muscle weakness . Every one point increase in sum score at discharge was associated with improved survival ( hazard ratio [ 95 % CI ] , 0.96 [ 0.94–0.98 ] ) , with similar findings longitudinally ( 0.95 [ 0.93–0.98 ] ) . Having weakness at discharge was associated with worse 5-year survival ( 1.75 [ 1.01–3.03 ] ) , but the association was attenuated ( 1.54 [ 0.82–2.89 ] ) when evaluated longitudinally over follow-up . Persisting and resolving trajectories of muscle weakness , occurring in 50 % of patients during follow-up , were associated with worse survival ( 3.01 [ 1.12 - 8.04 ] ; and 3.14 [ 1.40 - 7.03 ] , respectively ) compared to a trajectory of maintaining no muscle weakness . Conclusions : At hospital discharge , greater than one third of acute respiratory distress syndrome survivors had muscle weakness . Greater strength at discharge and throughout follow-up was associated with improved 5-year survival . In patients with post-ICU weakness , both persisting and resolving trajectories were commonly experienced and associated with worse survival during follow-up Background Diaphragm dysfunction in mechanically ventilated patients is associated with poor outcome . Maximal inspiratory pressure ( MIP ) can be used to evaluate inspiratory muscle function . However , it is unclear whether respiratory weakness is independently associated with long-term mortality . The aim of this study was to determine if low MIP is independently associated with one-year mortality . Methods We conducted a prospect i ve observational cohort study in an 18-bed ICU . Adults requiring at least 24 hours of mechanical ventilation with scheduled extubation and no evidence of pre-existing muscle weakness underwent MIP evaluation  just before extubation . Patients were divided into two groups : low MIP ( MIP ≤30 cmH2O ) and high MIP ( MIP > 30 cmH2O ) . Mortality was recorded for one year after extubation . For the survival analysis , the effect of low MIP was assessed using the log-rank test . The independent effect of low MIP on post mechanical ventilation mortality was analyzed using a multivariable Cox regression model . Results One hundred and twenty-four patients underwent  MIP evaluation ( median age 66 years ( 25th–75th percentile 56–74 ) , Simplified Acute Physiology Score ( SAPS ) 2 = 45 ( 33–57 ) , duration of mechanical ventilation 7 days ( 4–10 ) ) . Fifty-four percent of patients had low MIP . One-year mortality was 31 % ( 95 % CI 0.21 , 0.43 ) in the low MIP group and 7 % ( 95 % CI 0.02 , 0.16 ) in the high MIP group . After adjustment for SAPS 2 score , body mass index and duration of mechanical ventilation , low MIP was independently associated with one-year mortality ( hazard ratio 4.41 , 95 % CI 1.5 , 12.9 , p = 0.007 ) . Extubation failure was also associated with low MIP ( relative risk 3.0 , 95 % CI 1 , -9.6 ; p = 0.03 ) but tracheostomy and ICU length of stay were not . Conclusion Low MIP is frequent in patients on mechanical ventilation and is an independent risk factor for 
    Output:
    
ICU-acquired weakness increases risk of in-ICU , in-hospital and long-term mortality , duration of mechanical ventilation and of hospitalization and augments healthcare-related costs , increases likelihood of prolonged care in rehabilitation centers and reduces physical function and quality of life in the long term .
RCTs have shown preventive impact of avoiding hyperglycemia , of omitting early parenteral nutrition use and of minimizing sedation .
ICU-acquired weakness predisposes to adverse short- and long-term outcomes .
Only a few preventive , but no therapeutic , strategies exist .