Late evaluation of the relationship between morphological and functional renal changes and hypertension after non-operative treatment of high-grade renal injuries

Objective: To evaluate the anatomical and functional renal alterations and the association with post-traumatic arterial hypertension. Methods: The studied population included patients who sustained high grades renal injury (grades III to V) successfully non-operative management after staging by computed tomography over a 16-year period. Beyond the review of medical records, these patients were invited to the following protocol: clinical and laboratory evaluation, abdominal computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and ambulatory blood pressure monitoring. The hypertensive patients also were submitted to dynamic renal scintigraphy (Tc-99m EC), using captopril stimulation to verify renal vascular etiology. Results: Of the 31 patients, there were thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular lesions), and two grade V injuries. All the patients were asymptomatic and an average follow up post-injury of 6.4 years. None had abnormal BUN or seric creatinine. The percentage of renal volume reduction correlates with the severity as defined by OIS. There was no evidence of renal artery stenosis in Magnetic Resonance angiography (MRA). DMSA scanning demonstrated a decline in percentage of total renal function corresponding to injury severity (42.2 +/- 5.5% for grade III, 35.3 +/- 12.8% for grade IV, 13.5 +/- 19.1 for grade V). Six patients (19.4%) had severe compromised function (< 30%). There was statistically significant difference in the decrease in renal function between parenchymal and vascular causes for grade IV injuries (p < 0.001). The 24-hour ambulatory blood pressure monitoring detected nine patients (29%) with post-traumatic hypertension. All the patients were male, mean 35.6 years, 77.8 % had a familial history of arterial hypertension, 66.7% had grade III renal injury, and average post-injury time was 7.8 years. Seven patients had negative captopril renography. Conclusions: Late results of renal function after conservative treatment of high grades renal injuries are favorable, except for patients with grades IV with vascular injuries and grade V renal injuries. Moreover, arterial hypertension does not correlate with the grade of renal injury or reduction of renal function.

Infrared (810 nm) Low-Level Laser Therapy in Experimental Model of Strain-Induced Skeletal Muscle Injury in Rats: Effects on Functional Outcomes

Muscle strains are among the most prevalent causes for athletes absence from sport activities. Low-level laser therapy (LLLT) has recently emerged as a potential contender to nonsteroidal anti-inflammatory drugs in muscle strain treatment. In this work we investigated effects of LLLT and diclofenac on functional outcomes in the acute stage after muscle strain injury in rats. Muscle strain was induced by overloading the tibialis anterior muscle of rats during anesthesia. The injured groups received either no treatment, or a single treatment with diclofenac 30 min prior to injury, or LLLT (810 nm, 100 mW) with doses of 1, 3, 6 or 9 J, at 1 h after injury. Functional outcome measures included a walking index and assessment of electrically induced muscle performance. All treatments (except 9 J LLLT) significantly improved the walking index 12 h postinjury compared with the untreated group. The 3 J group also showed a significantly better walking index than the drug group. All treatments significantly improved muscle performance at 6 and 12 h. LLLT dose of 3 J was as effective as the pharmacological agent in improving functional outcomes in the early phase after a muscle strain injury in rats.

Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography Main Results From the Randomized Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)

Background-It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury. Methods and Results-We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25; P = 0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P = 0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment. Conclusions-In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.

Prevention of Intradialytic Hypotension in Patients with Acute Kidney Injury Submitted to Sustained Low-Efficiency Dialysis

Objectives: This study evaluated the effects of a protocol aiming to reduce hypotension in acute kidney injury (AKI) patients submitted to sustained low-efficiency dialysis (SLED). Methods: Patients were randomly assigned to two SLED prescriptions-control group, dialysate temperature was 37.0 degrees C with a fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and profiling group, dialysate temperature was 35.5 degrees C with a variable sodium concentration [150-138 mEq/L] and UF rate. Results: Sixty-two SLED sessions were evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score. Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both groups. The profiling group had significantly less hypotension episodes (23% vs. 57% in control, p = 0.009) and achieved higher UF volume (2.23 +/- 1.25 L vs. 1.59 +/- 1.03 L in control, p = 0.04) when compared with control group. Conclusions: SLED protocol with modulation of dialysate temperature, sodium, and UF profiling showed similar efficacy but less intradialytic hypotension when compared with a standard SLED prescription.

Long-Term Follow-Up of Patients after Acute Kidney Injury: Patterns of Renal Functional Recovery

Background and Objectives: Patients who survive acute kidney injury (AKI), especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. Design, Setting, Participants, & Measurements: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA) for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD) or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value >= 60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. Results: The median length of follow-up was 50 months (30-90 months). All patients had stabilized their glomerular filtration rates by 18 months and 83% of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19%) at discharge and in 54 (64%) by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p < 0.0001) and serum creatinine at hospital discharge (OR 2.48, p = 0.007) were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and need for dialysis, was not associated with non renal recovery. Conclusions: Renal recovery must be evaluated no earlier than one year after an acute kidney injury episode. Nephrology referral should be considered mainly for older patients and those with elevated serum creatinine at hospital discharge.

Renal Function at Hospital Admission and Mortality Due to Acute Kidney Injury after Myocardial Infarction

Background: The role of an impaired estimated glomerular filtration rate (eGFR) at hospital admission in the outcome of acute kidney injury (AKI) after acute myocardial infarction (AMI) has been underreported. The aim of this study was to assess the influence of an admission eGFR<60 mL/min/1.73 m(2) on the incidence and early and late mortality of AMI-associated AKI. Methods: A prospective study of 828 AMI patients was performed. AKI was defined as a serum creatinine increase of >= 50% from the time of admission (RIFLE criteria) in the first 7 days of hospitalization. Patients were divided into subgroups according to their eGFR upon hospital admission (MDRD formula, mL/min/1.73 m(2)) and the development of AKI: eGFR >= 60 without AKI, eGFR<60 without AKI, eGFR >= 60 with AKI and eGFR<60 with AKI. Results: Overall, 14.6% of the patients in this study developed AKI. The admission eGFR had no impact on the incidence of AKI. However, the admission eGFR was associated with the outcome of AMI-associated AKI. The adjusted hazard ratios (AHR, Cox multivariate analysis) for 30-day mortality were 2.00 (95% CI 1.11-3.61) for eGFR, 60 without AKI, 4.76 (95% CI 2.45-9.26) for eGFR >= 60 with AKI and 6.27 (95% CI 3.20-12.29) for eGFR, 60 with AKI. Only an admission eGFR of <60 with AKI was significantly associated with a 30-day to 1-year mortality hazard (AHR 3.05, 95% CI 1.50-6.19). Conclusions: AKI development was associated with an increased early mortality hazard in AMI patients with either preserved or impaired admission eGFR. Only the association of impaired admission eGFR and AKI was associated with an increased hazard for late mortality among these patients.

Duration of dual antiplatelet therapy and outcomes after coronary stenting with the genous (TM) bio-engineered R stent (TM) in patients from the e-healing registry

Objective: We investigated the relation between duration of dual antiplatelet therapy (DAPT) and clinical outcomes up to 12 months after Genous (TM) endothelial progenitor cell capturing R stent (TM) placement in patients from the e-HEALING registry. Background: Cessation of (DAPT) has been shown to be associated with the occurrence of stent thrombosis (ST). After Genous placement, 1 month of DAPT is recommended. Methods: Patients were analyzed according to continuation or discontinuation of DAPT at a 30-day and 6-month landmark, excluding patients with events before the landmark. Each landmark was a new baseline, and outcomes were followed up to 12 months after stenting. The main outcome for our current analysis was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction and target vessel revascularization. Secondary outcomes included ST. (Un)adjusted hazard ratios (HR) for TVF were calculated with Cox regression. Results: No difference was observed in the incidence of TVF [HR: 1.03; 95% confidence intervals (CI): 0.651.65, P = 0.89] in patients continuing DAPT (n = 4,249) at 30 days versus patients stopped (n = 309), and HR: 0.82 (95% CI: 0.551.23, P = 0.34) in patients continuing DAPT (n = 2,654) at 6 months versus patients stopped [n = 1,408] DAPT). Furthermore, no differences were observed in ST. Even after addition of identified independent predictors for TVF, adjusted TVF hazards were comparable. Conclusions: In a post-hoc analysis of e-HEALING, duration of DAPT was not associated with the occurrence of the outcomes TVF or ST. The Genous stent may be an attractive treatment especially in patients at increased risk for (temporary) cessation of DAPT or bleeding. (C) 2011 Wiley Periodicals, Inc.

Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice

Recent investigation of the intestine following ischemia and reperfusion (I/R) has revealed that nitric oxide synthase (NOS) neurons are more strongly affected than other neuron types. This implies that NO originating from NOS neurons contributes to neuronal damage. However, there is also evidence of the neuroprotective effects of NO. In this study, we compared the effects of I/R on the intestines of neuronal NOS knockout (nNOS(-/-)) mice and wild-type mice. I/R caused histological damage to the mucosa and muscle and infiltration of neutrophils into the external muscle layers. Damage to the mucosa and muscle was more severe and greater infiltration by neutrophils occurred in the first 24 h in nNOS(-/-) mice. Immunohistochemistry for the contractile protein, alpha-smooth muscle actin, was used to evaluate muscle damage. Smooth muscle actin occurred in the majority of smooth muscle cells in the external musculature of normal mice but was absent from most cells and was reduced in the cytoplasm of other cells following I/R. The loss was greater in nNOS(-/-) mice. Basal contractile activity of the longitudinal muscle and contractile responses to nerve stimulation or a muscarinic agonist were reduced in regions subjected to I/R and the effects were greater in nNOS(-/-) mice. Reductions in responsiveness also occurred in regions of operated mice not subjected to I/R. This is attributed to post-operative ileus that is not significantly affected by knockout of nNOS. The results indicate that deleterious effects are greater in regions subjected to I/R in mice lacking nNOS compared with normal mice, implying that NO produced by nNOS has protective effects that outweigh any damaging effect of this free radical produced by enteric neurons.

N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation

Campos R, Shimizu MH, Volpini RA, de Bragan a AC, Andrade L, Lopes FD, Olivo C, Canale D, Seguro AC. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 302: L640-L650, 2012. First published January 20, 2012; doi: 10.1152/ajplung.00097.2011.-Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the alpha-subunit of the epithelial sodium channel (alpha-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, alpha-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis.

Association between systemic corticosteroids and outcomes of intensive care unit-acquired pneumonia

Objective: The use of corticosteroids is frequent in critically-ill patients. However, little information is available on their effects in patients with intensive care unit acquired pneumonia. We assessed patients' characteristics, microbial etiology, inflammatory response, and outcomes of previous corticosteroid use in patients with intensive care unit acquired pneumonia. Design: Prospective observational study. Setting: Intensive care units of a university teaching hospital. Patients: Three hundred sixteen patients with intensive care unit acquired pneumonia. Patients were divided according to previous systemic steroid use at onset of pneumonia. Interventions: None. Measurements and Main Results: Survival at 28 days was analyzed using Cox regression, with adjustment for the propensity for receiving steroid therapy. One hundred twenty-five (40%) patients were receiving steroids at onset of pneumonia. Despite similar baseline clinical severity, steroid treatment was associated with decreased 28-day survival (adjusted hazard ratio for propensity score and mortality predictors 2.503; 95% confidence interval 1.176-5.330; p = .017) and decreased systemic inflammatory response. In post hoc analyses, steroid treatment had an impact on survival in patients with nonventilator intensive care unit acquired pneumonia, those with lower baseline severity and organ dysfunction, and those without etiologic diagnosis or bacteremia. The cumulative dosage of corticosteroids had no significant effect on the risk of death, but bacterial burden upon diagnosis was higher in patients receiving steroid therapy. Conclusions: In critically-ill patients, systemic corticosteroids should be used very cautiously because this treatment is strongly associated with increased risk of death in patients with intensive care unit acquired pneumonia, particularly in the absence of established indications and in patients with lower baseline severity. Decreased inflammatory response may result in delayed clinical suspicion of intensive care unit acquired pneumonia and higher bacterial count. (Crit Care Med 2012; 40:2552-2561)

Nursing diagnoses in trauma victims with fatal outcomes in the emergency scenario

The objective of this study was to identify and analyze the nursing diagnoses that constitute risk factors for death in trauma victims in the first 6 hours post-event. This is a cross-sectional, descriptive and exploratory study using quantitative analysis. A total of 406 patients were evaluated over six months of data collection in a tertiary hospital in the municipality of Sao Paulo, according to an instrument created for this purpose. Of the total, 44 (10.7%) suffered death. Multivariate analysis indicated the nursing diagnoses ineffective respiratory pattern, impaired spontaneous ventilation, risk of bleeding and risk of ineffective gastrointestinal tissue perfusion as risk factors for death and ineffective airway clearance, impaired comfort, and acute pain as protective factors, data that can direct health teams for different interventionist actions faced with the complexity of the trauma.

The Real Importance of Pre-Existing Comorbidities on Long-Term Mortality after Acute Kidney Injury

Background: The causes of death on long-term mortality after acute kidney injury (AKI) have not been well studied. The purpose of the study was to evaluate the role of comorbidities and the causes of death on the long-term mortality after AKI. Methodology/Principal Findings: We retrospectively studied 507 patients who experienced AKI in 2005-2006 and were discharged free from dialysis. In June 2008 (median: 21 months after AKI), we found that 193 (38%) patients had died. This mortality is much higher than the mortality of the population of Sao Paulo City, even after adjustment for age. A multiple survival analysis was performed using Cox proportional hazards regression model and showed that death was associated with Khan's index indicating high risk [adjusted hazard ratio 2.54 (1.38-4.66)], chronic liver disease [1.93 (1.15-3.22)], admission to non-surgical ward [1.85 (1.30-2.61)] and a second AKI episode during the same hospitalization [1.74 (1.12-2.71)]. The AKI severity evaluated either by the worst stage reached during AKI (P=0.20) or by the need for dialysis (P=0.12) was not associated with death. The causes of death were identified by a death certificate in 85% of the non-survivors. Among those who died from circulatory system diseases (the main cause of death), 59% had already suffered from hypertension, 34% from diabetes, 47% from heart failure, 38% from coronary disease, and 66% had a glomerular filtration rate <60 previous to the AKI episode. Among those who died from neoplasms, 79% already had the disease previously. Conclusions: Among AKI survivors who were discharged free from dialysis the increased long-term mortality was associated with their pre-existing chronic conditions and not with the severity of the AKI episode. These findings suggest that these survivors should have a medical follow-up after hospital discharge and that all efforts should be made to control their comorbidities.

Cannabidiol-treated Rats Exhibited Higher Motor Score After Cryogenic Spinal Cord Injury

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.

Upper Brachial Plexus Injuries: Grafts vs Ulnar Fascicle Transfer to Restore Biceps Muscle Function

BACKGROUND: Nerve transfers or graft repairs in upper brachial plexus palsies are 2 available options for elbow flexion recovery. OBJECTIVE: To assess outcomes of biceps muscle strength when treated either by grafts or nerve transfer. METHODS: A standard supraclavicular approach was performed in all patients. When roots were available, grafts were used directed to proximal targets. Otherwise, a distal ulnar nerve fascicle was transferred to the biceps branch. Elbow flexion strength was measured with a dynamometer, and an index comparing the healthy arm and the operated-on side was developed. Statistical analysis to compare both techniques was performed. RESULTS: Thirty-five patients (34 men) were included in this series. Mean age was 28.7 years (standard deviation, 8.7). Twenty-two patients (62.8%) presented with a C5-C6 injury, whereas 13 patients (37.2%) had a C5-C6-C7 lesion. Seventeen patients received reconstruction with grafts, and 18 patients were treated with a nerve transfer from the ulnar nerve to the biceps. The trauma to surgery interval (mean, 7.6 months in both groups), strength in the healthy arm, and follow-up duration were not statistically different. On the British Medical Research Council muscle strength scale, 8 of 17 (47%) patients with a graft achieved >= M3 biceps flexion postoperatively, vs 16 of 18 (88%) post nerve transfers (P = .024). This difference persisted when a muscle strength index assessing improvement relative to the healthy limb was used (P = .031). CONCLUSION: The results obtained from ulnar nerve fascicle transfer to the biceps branch were superior to those achieved through reconstruction with grafts.

Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome A Meta-analysis

Context Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS. Objective To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS. Data Sources MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012. Study Selection Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations. Data Extraction Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. Data Synthesis Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I-2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I-2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I-2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I-2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, -0.51; 95% CI, -0.70 to -0.32; I-2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I-2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, -0.06 to 0.27; I-2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results. Conclusions Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation. JAMA. 2012;308(16):1651-1659 www.jama.com