Postoperative virtual reality for recovery after bariatric surgery: study protocol for a randomised clinical trial.

Background: Enhanced Recovery After Surgery (ERAS) protocols for bariatric surgery improve clinical outcomes. However, the impact of ERAS protocols on patient satisfaction is unknown. Virtual reality has been implemented as an effective adjunct to standard analgesic regimens. This study seeks to find out if immersive virtual reality in the immediate postoperative period could improve the subjective quality of recovery and further reduce opioid requirements for bariatric surgery patients compared with ERAS care alone. Methods: This is a single-centre, randomised clinical trial of patients recovering from laparoscopic bariatric surgery. Once in the post-anaesthesia care unit (PACU), participants will receive either an immersive virtual reality plus ERAS protocol or ERAS protocol alone. The primary outcome will be the Quality of Recovery-15 (QoR-15) score at PACU discharge. Secondary outcomes include PACU opioid requirements, length of PACU stay, PACU pain scores, QoR-15 score on postoperative day 1, hospital length of stay, opioid requirements, and opioid-related adverse effects until hospital discharge. Conclusions: Positive findings from this study could introduce virtual reality as a non-pharmacological adjunct during PACU care that improves subjective recovery for patients undergoing bariatric surgery. Clinical trial registration: NCT04754165.

Early-Onset Invasive Pulmonary Aspergillosis in a Liver Transplant Patient: A Case Report.

Invasive pulmonary aspergillosis (IPA) in liver transplant patients remains rare but exceedingly fatal. The diagnostic challenges associated with this condition are compounded by its infrequent onset within the first two weeks following transplantation. Moreover, therapeutic management is complex due to the intricate drug interactions between triazole antifungals and calcineurin inhibitor immunosuppressants. We present the case of a 63-year-old male who underwent uncomplicated liver transplantation (LT) and developed early-onset IPA. Despite maximal efforts, the patient expired. This report aims to underscore the vital importance of timely diagnosis and therapy in preventing the insidious progression of invasive disease and subsequent mortality.

Outcomes With Single-Site Dual-Lumen Versus Multisite Cannulation for Adults With COVID-19 Respiratory Failure Receiving Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To determine whether multisite versus single-site dual-lumen (SSDL) cannulation is associated with outcomes for COVID-19 patients requiring venovenous extracorporeal membrane oxygenation (VV-ECMO). DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization Registry. Propensity score matching (2:1 multisite vs SSDL) was used to control for confounders. PATIENTS: The matched cohort included 2,628 patients (1,752 multisite, 876 SSDL) from 170 centers. The mean ( sd ) age in the entire cohort was 48 (11) years, and 3,909 (71%) were male. Patients were supported with mechanical ventilation for a median (interquartile range) of 79 (113) hours before VV-ECMO support. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was 90-day survival. Secondary outcomes included survival to hospital discharge, duration of ECMO support, days free of ECMO support at 90 days, and complication rates. MAIN RESULTS: There was no difference in 90-day survival (49.4 vs 48.9%, p = 0.66), survival to hospital discharge (49.8 vs 48.2%, p = 0.44), duration of ECMO support (17.9 vs 17.1 d, p = 0.82), or hospital length of stay after cannulation (28 vs 27.4 d, p = 0.37) between multisite and SSDL groups. More SSDL patients were extubated within 24 hours (4% vs 1.9%, p = 0.001). Multisite patients had higher ECMO flows at 24 hours (4.5 vs 4.1 L/min, p < 0.001) and more ECMO-free days at 90 days (3.1 vs 2.0 d, p = 0.02). SSDL patients had higher rates of pneumothorax (13.9% vs 11%, p = 0.03). Cannula site bleeding (6.4% vs 4.7%, p = 0.03), oxygenator failure (16.7 vs 13.4%, p = 0.03), and circuit clots (5.5% vs 3.4%, p = 0.02) were more frequent in multisite patients. CONCLUSIONS: In this retrospective study of COVID-19 patients requiring VV-ECMO, 90-day survival did not differ between patients treated with a multisite versus SSDL cannulation strategy and there were only modest differences in major complication rates. These findings do not support the superiority of either cannulation strategy in this setting.

Anesthetic Preferences for Cardiac Anesthesia: A Survey of the Society of Cardiovascular Anesthesiologists.

BACKGROUND: Volatile anesthetics have been historically preferred for cardiac anesthesia, but the evidence for their superiority to intravenous agents is mixed. We conducted a survey to better understand the current state of practice and the rationale behind provider preferences for anesthesia for cardiac surgery with cardiopulmonary bypass. We hypothesized that anesthetic preference would vary considerably among surveyed providers without a clear majority, as would the rationale behind those preferences. METHODS: Email invitations were sent to members of the Society of Cardiovascular Anesthesiologists, who were asked to identify the anesthetics or sedatives they typically prefer to administer during induction, prebypass, bypass, postbypass, and postoperative periods and why they prefer those agents. Members' beliefs regarding the importance of anesthetics on postoperative outcomes were also assessed. RESULTS: Invitations were sent on 2 separate dates to 3328 and 3274 members, of whom 689 (21%) responded. The median (interquartile range [IQR]) respondent age was 45 (37-56) years, 79% were men, and 75% were fellowship trained. The most frequently chosen drug for induction was propofol (80%). Isoflurane was the most frequently selected primary agent for the prebypass (57%), bypass (62%), and postbypass periods (50%). Sevoflurane was the second most frequently selected (30%; 17%, and 24%, respectively). Propofol was the third most frequently selected agent for the bypass (14%) and postbypass periods (17%). Ease of use was the most frequently selected reason for administering isoflurane and sevoflurane for each period. During bypass, the second most frequently selected rationale for using isoflurane and sevoflurane was institutional practice. A total of 76% responded that the perfusionist typically delivers the bypass anesthetic. Ischemic preconditioning, organ protection, and postoperative cognitive function were infrequently selected as rationales for preferring the volatile anesthetics. Most respondents (73%) think that anesthetics have organ-protective properties, especially isoflurane (74%) and sevoflurane (59%), and 72% believed that anesthetic choice contributes to patient outcome. The median (IQR) agreement (0 = strongly disagree to 100 = strongly agree) was 72 (63-85) for the statement that "inhaled anesthetics are an optimal maintenance anesthetic for cardiac surgery." CONCLUSIONS: In a survey of cardiac anesthesiologists, a majority of respondents indicated that they prefer volatile anesthetics for maintenance of anesthesia, that anesthetic selection impacts patient outcomes, and that volatile anesthetics have organ-protective properties. The members' rationales for preferring these agents possibly reflect that practical considerations, such as ease of use, effectiveness, and institutional practice, also influence anesthetic selection during cardiac surgery in addition to considerations such as organ protection.

Virtual reality immersion compared to monitored anesthesia care for hand surgery: A randomized controlled trial.

INTRODUCTION: Common anesthesia practice for hand surgery combines a preoperative regional anesthetic and intraoperative monitored anesthesia care (MAC). Despite adequate regional anesthesia, patients may receive doses of intraoperative sedatives which can result in oversedation and potentially avoidable complications. VR could prove to be a valuable tool for patients and providers by distracting the mind from processing noxious stimuli resulting in minimized sedative use and reduced risk of oversedation without negatively impacting patient satisfaction. Our hypothesis was that intraoperative VR use reduces sedative dosing during elective hand surgery without detracting from patient satisfaction as compared to a usual care control. METHODS: Forty adults undergoing hand surgery were randomized to receive either intraoperative VR in addition to MAC, or usual MAC. Patients in both groups received preoperative regional anesthesia at provider discretion. Intraoperatively, the VR group viewed programming of their choice via a head-mounted display. The primary outcome was intraoperative propofol dose per hour (mg · hr-1). Secondary outcomes included patient reported pain and anxiety, overall satisfaction, functional outcome, and post anesthesia care unit (PACU) length of stay (LOS). RESULTS: Of the 40 enrolled patients, 34 completed the perioperative portion of the trial. VR group patients received significantly less propofol per hour than the control group (Mean (±SD): 125.3 (±296.0) vs 750.6 (±334.6) mg · hr-1, p<0.001). There were no significant differences between groups in patient reported overall satisfaction, (0-100 scale, Median (IQR) 92 (77-100) vs 100 (100-100), VR vs control, p = 0.087). There were no significant differences between groups in PACU pain scores, perioperative opioid analgesic dose, or in postoperative functional outcome. PACU LOS was significantly decreased in the VR group (53.0 (43.0-72.0) vs 75.0 (57.5-89.0) min, p = 0.018). CONCLUSION: VR immersion during hand surgery led to significant reductions in intraoperative propofol dose and PACU LOS without negatively impacting key patient reported outcomes.

Anesthetics to Prevent Lung Injury in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: To investigate if sevoflurane based anesthesia is superior to propofol in preventing lung inflammation and preventing postoperative pulmonary complications. DESIGN: Randomized controlled trial. SETTING: Single tertiary care university hospital. PARTICIPANTS: Forty adults undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 ratio to anesthetic maintenance with sevoflurane or propofol. MEASUREMENTS AND MAIN RESULTS: Blood and bronchoalveolar lavage fluid was sampled before and after bypass to measure pulmonary inflammation using a biomarker panel. The change in bronchoalveolar lavage concentration of tumor necrosis factor alpha (TNFα) was the primary outcome. Secondary outcomes included lung inflammation defined as changes in other biomarkers and postoperative pulmonary complications. There were no significant differences between groups in the change in bronchoalveolar lavage TNFα concentration (median [IQR] change, 17.24 [1.11-536.77] v 101.51 [1.47-402.84] pg/mL, sevoflurane v propofol, p = 0.31). There was a significantly lower postbypass concentration of plasma interleukin 8 (median [IQR], 53.92 [34.5-55.91] v 66.92 [53.03-94.44] pg/mL, p = 0.04) and a significantly smaller postbypass increase in the plasma receptor for advanced glycosylation end products (median [IQR], 174.59 [73.59-446.06] v 548.22 [193.15-852.39] pg/mL, p = 0.03) in the sevoflurane group compared with propofol. The incidence of postoperative pulmonary complications was 100% in both groups, with high rates of pleural effusion (17/18 [94.44%] v 19/22 [86.36%], p = 0.39) and hypoxemia (16/18 [88.88%] v 22/22 [100%], p = 0.11). CONCLUSIONS: Sevoflurane anesthesia during cardiac surgery did not consistently prevent lung inflammation or prevent postoperative pulmonary complications compared to propofol. There were significantly lower levels of 2 plasma biomarkers specific for lung injury and inflammation in the sevoflurane group.

Intraoperative Oxygen Practices in Cardiac Surgery: A National Survey.

OBJECTIVE: To describe the current nationwide perspectives and practice regarding intraoperative oxygen titration in cardiac surgery. DESIGN: Prospective, observational survey. SETTING: Hospitals across the United States. PARTICIPANTS: Cardiovascular anesthesiologists and perfusionists. INTERVENTIONS: Expert- and consensus-derived electronic surveys were sent to perfusionists and cardiac anesthesiologists to evaluate the current intraoperative practices around oxygen administration. Providers were asked about individual intraoperative oxygen titration practices used at different stages of cardiac surgical procedures. Anonymous responses were collected in the Research Electronic Data Capture (REDCap). MEASUREMENTS AND MAIN RESULTS: A total of 3,335 providers were invited to participate, of whom 554 (317 anesthesiologists and 237 perfusionists) were included in the final analysis (17% response rate). During cardiopulmonary bypass (CPB), perfusionists reported a median (interquartile range [IQR]) target range from 150 (110-220)-to-325 mmHg (250-400), while anesthesiologists reported a significantly lower target range from 90 (70-150)-to-250 mmHg (158-400) (p values <0.0001 and 0.02, respectively). This difference was most pronounced at lower partial pressure of arterial oxygen (PaO2) ranges. The median PaO2 considered "too low" by perfusionists was 100 mmHg (IQR 80-125), whereas it was 60 mmHg (IQR 60-75) for anesthesiologists, who reported for both off and on bypass. The median PaO2 considered "too high" was 375 mmHg (IQR 300-400) for perfusionists and 300 mmHg (IQR 200-400) for anesthesiologists. Anesthesiologists, therefore, reported more comfort with significantly lower PaO2 values (p < 0.0001), and considered a higher PaO2 value less desirable compared with perfusionists (p < 0.0001). CONCLUSIONS: This survey demonstrated there was wide variation in oxygen administration practices between perfusionists and anesthesiologists. Hyperoxygenation was more common while on CPB.

Rapid weight gain following weight cutting in male professional boxers.

OBJECTIVES: Weight classifications are used in boxing and other combat sports to match opponents of similar size. Professional boxers commonly engage in a potentially harmful practice known as rapid weight loss or 'weight cutting' to make weight the day prior to competition before rehydrating and refueling. This investigation describes the prevalence and magnitude of rapid weight gain in boxers following weigh-in as well as differences in practice with respect to weight class and promotion. METHODS: This analysis describes official weight data from male professional boxers collected by the California State Athletic Commission between 2015 and 2018. A total of 399 athletes were included in the study. RESULTS: Among included athletes, 389 (97.5%) athletes gained weight between official weigh-in and competition. Total absolute body mass gained was 4.4 ± 2.2 kg corresponding to a total relative body mass gain of 7.2 ± 3.5%. Boxers competing in international promotions gained significantly more body mass than regional competitors (8.0 ± 3.0% vs. 6.6 ± 3.7%; p < 0.001). In total, 82 (20.6%) athletes gained 10% body mass or more before competition. More international competitors reached this 10% threshold than regional competitors (25.3% vs. 17.4%; p = 0.03). CONCLUSIONS: These findings indicate high prevalence and magnitude of RWG in professional boxing, particularly in boxers competing in elite international promotions.

Sleep, Pain, and Cognition: Modifiable Targets for Optimal Perioperative Brain Health.

The prevention of perioperative neurocognitive disorders is a priority for patients, families, clinicians, and researchers. Given the multiple risk factors present throughout the perioperative period, a multicomponent preventative approach may be most effective. The objectives of this narrative review are to highlight the importance of sleep, pain, and cognition on the risk of perioperative neurocognitive disorders and to discuss the evidence behind interventions targeting these modifiable risk factors. Sleep disruption is associated with postoperative delirium, but the benefit of sleep-related interventions is uncertain. Pain is a risk factor for postoperative delirium, but its impact on other postoperative neurocognitive disorders is unknown. Multimodal analgesia and opioid avoidance are emerging as best practices, but data supporting their efficacy to prevent delirium are limited. Poor preoperative cognitive function is a strong predictor of postoperative neurocognitive disorder, and work is ongoing to determine whether it can be modified to prevent perioperative neurocognitive disorders.

Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19.

PURPOSE: Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19). METHODS: We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO2/FiO2 < 100). Patients were followed until hospital discharge, death, or a minimum of 60 days. We adjusted for confounding using a multivariable Cox model. RESULTS: Among the 190 patients treated with ECMO, the median age was 49 years (IQR 41-58), 137 (72.1%) were men, and the median PaO2/FiO2 prior to ECMO initiation was 72 (IQR 61-90). At 60 days, 63 patients (33.2%) had died, 94 (49.5%) were discharged, and 33 (17.4%) remained hospitalized. Among the 1297 patients eligible for the target trial emulation, 45 of the 130 (34.6%) who received ECMO died, and 553 of the 1167 (47.4%) who did not receive ECMO died. In the primary analysis, patients who received ECMO had lower mortality than those who did not (HR 0.55; 95% CI 0.41-0.74). Results were similar in a secondary analysis limited to patients with PaO2/FiO2 < 80 (HR 0.55; 95% CI 0.40-0.77). CONCLUSION: In select patients with severe respiratory failure from COVID-19, ECMO may reduce mortality.

Prevalence of Clostridioides difficile Infection in Critically Ill Patients with Extreme Leukocytosis and Diarrhea.

While early empiric antibiotic therapy is beneficial for patients presenting with sepsis, the presentation of sepsis from Clostridioides difficile (formerly Clostridium difficile) infection (CDI) has not been well studied in large cohorts. We sought to determine whether the combination of extreme leukocytosis and diarrhea was strongly predictive of CDI in a cohort of 8659 patients admitted to the intensive care unit. We found that CDI was present in 15.0% (95% CI, 12.1-18.3%) of patients with extreme leukocytosis and diarrhea and that mortality for those with CDI, diarrhea, and extreme leukocytosis was 33.8% (95% CI, 23.2-44.3%). These data support consideration of empiric treatment for CDI in unstable critically ill patients with extreme leukocytosis and diarrhea, along with treatment of other possible sources of sepsis as appropriate. Empiric treatment for CDI can usually be discontinued promptly, along with narrowing of other broad-spectrum antimicrobial coverage, if a sensitive C. difficile test is negative.

Intraoperative Oxygen Concentration and Neurocognition after Cardiac Surgery.

BACKGROUND: Despite evidence suggesting detrimental effects of perioperative hyperoxia, hyperoxygenation remains commonplace in cardiac surgery. Hyperoxygenation may increase oxidative damage and neuronal injury leading to potential differences in postoperative neurocognition. Therefore, this study tested the primary hypothesis that intraoperative normoxia, as compared to hyperoxia, reduces postoperative cognitive dysfunction in older patients having cardiac surgery. METHODS: A randomized double-blind trial was conducted in patients aged 65 yr or older having coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 100 patients were randomized to one of two intraoperative oxygen delivery strategies. Normoxic patients (n = 50) received a minimum fraction of inspired oxygen of 0.35 to maintain a Pao2 above 70 mmHg before and after cardiopulmonary bypass and between 100 and 150 mmHg during cardiopulmonary bypass. Hyperoxic patients (n = 50) received a fraction of inspired oxygen of 1.0 throughout surgery, irrespective of Pao2 levels. The primary outcome was neurocognitive function measured on postoperative day 2 using the Telephonic Montreal Cognitive Assessment. Secondary outcomes included neurocognitive function at 1, 3, and 6 months, as well as postoperative delirium, mortality, and durations of mechanical ventilation, intensive care unit stay, and hospital stay. RESULTS: The median age was 71 yr (interquartile range, 68 to 75), and the median baseline neurocognitive score was 17 (16 to 19). The median intraoperative Pao2 was 309 (285 to 352) mmHg in the hyperoxia group and 153 (133 to 168) mmHg in the normoxia group (P < 0.001). The median Telephonic Montreal Cognitive Assessment score on postoperative day 2 was 18 (16 to 20) in the hyperoxia group and 18 (14 to 20) in the normoxia group (P = 0.42). Neurocognitive function at 1, 3, and 6 months, as well as secondary outcomes, were not statistically different between groups. CONCLUSIONS: In this randomized controlled trial, intraoperative normoxia did not reduce postoperative cognitive dysfunction when compared to intraoperative hyperoxia in older patients having cardiac surgery. Although the optimal intraoperative oxygenation strategy remains uncertain, the results indicate that intraoperative hyperoxia does not worsen postoperative cognition after cardiac surgery.

Prevention of Early Postoperative Decline: A Randomized, Controlled Feasibility Trial of Perioperative Cognitive Training.

BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction (POCD) are common after cardiac surgery and contribute to an increased risk of postoperative complications, longer length of stay, and increased hospital mortality. Cognitive training (CT) may be able to durably improve cognitive reserve in areas deficient in delirium and POCD and, therefore, may potentially reduce the risk of these conditions. We sought to determine the feasibility and potential efficacy of a perioperative CT program to reduce the incidence of postoperative delirium and POCD in older cardiac surgery patients. METHODS: Randomized controlled trial at a single tertiary care center. Participants included 45 older adults age 60-90 undergoing cardiac surgery at least 10 days from enrollment. Participants were randomly assigned in a 1:1 fashion to either perioperative CT via a mobile device or a usual care control. The primary outcome of feasibility was evaluated by enrollment patterns and adherence to protocol. Secondary outcomes of postoperative delirium and POCD were assessed using the Confusion Assessment Method and the Montreal Cognitive Assessment, respectively. Patient satisfaction was assessed via a postoperative survey. RESULTS: Sixty-five percent of eligible patients were enrolled. Median (interquartile range [IQR]) adherence (as a percentage of prescribed minutes played) was 39% (20%-68%), 6% (0%-37%), and 19% (0%-56%) for the preoperative, immediate postoperative, and postdischarge periods, respectively. Median (IQR) training times were 245 (136-536), 18 (0-40), and 122 (0-281) minutes for each period, respectively. The incidence of postoperative delirium (CT group 5/20 [25%] versus control 3/20 [15%]; P = .69) and POCD (CT group 53% versus control 37%; P = .33) was not significantly different between groups for either outcome in this limited sample. CT participants reported a high level of agreement (on a scale of 0-100) with statements that the program was easy to use (median [IQR], 87 [75-97]) and enjoyable (85 [79-91]). CT participants agreed significantly more than controls that their memory (median [IQR], 75 [54-82] vs 51 [49-54]; P = .01) and thinking ability (median [IQR], 78 [64-83] vs 50 [41-68]; P = .01) improved as a result of their participation in the study. CONCLUSIONS: A CT program designed for use in the preoperative period is an attractive target for future investigations of cognitive prehabilitation in older cardiac surgery patients. Changes in the functionality of the program and enrichment techniques may improve adherence in future trials. Further investigation is necessary to determine the potential efficacy of cognitive prehabilitation to reduce the risk of postoperative delirium and POCD.

Intraoperative oxygen concentration and neurocognition after cardiac surgery: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication of cardiac surgery. Studies have identified potentially injurious roles for cardiopulmonary bypass (CPB) and subsequent reperfusion injury. Cognitive dysfunction has also been linked to the deleterious effects of hyperoxia following ischemia-reperfusion injuries in several disease states, but there has been surprisingly little study into the role of hyperoxia in reperfusion injury after CPB. The potential for tightly regulated intraoperative normoxia to ameliorate the neurocognitive decline following cardiac surgery has not been investigated in a prospective manner. We hypothesize that the use of a protocolized management strategy aimed towards maintenance of an intraoperative normoxic level of oxygen, as opposed to hyperoxia, will reduce the incidence of POCD in older patients undergoing cardiac surgery. METHODS/DESIGN: One hundred patients aged 65 years and older undergoing non-emergency coronary artery bypass grafting surgery on cardiopulmonary bypass will be enrolled in this prospective, randomized, controlled trial. Subjects will be randomized to receive a fraction of inspired oxygen of either 35% or 100% while under general anesthesia throughout the intraoperative period. The primary outcome measure will be the incidence of POCD in the acute postoperative phase and up to 6 months. The assessment of neurocognition will be undertaken by trained personnel, blinded to study group, with the telephone Montreal Cognitive Assessment (t-MoCA) tool. Secondary outcome measures will include assessment of delirium using the Confusion Assessment Method (CAM and CAM-ICU), as well as time to extubation, days of mechanical ventilation, length of ICU and hospital stay and mortality at 6 months. With the aim of later identifying mechanistic aspects of the effect of oxygen tension, blood, urine, and atrial tissue specimens will be taken at various time points during the perioperative period and later analyzed. DISCUSSION: This trial will be one of the first randomized controlled studies to prospectively assess the relationship between intraoperative oxygen levels and postoperative neurocognition in cardiac surgery. It addresses a promising biological avenue of intervention in this vulnerable aging population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02591589 , registered February 13, 2015.

The Effect of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Hemodynamics.

BACKGROUND: Lung protective ventilation has not been evaluated in patients with brain injury. It is unclear whether applying positive end-expiratory pressure (PEEP) adversely affects intracranial pressure (ICP) and cerebral perfusion pressure (CPP). We aimed to evaluate the effect of PEEP on ICP and CPP in a large population of patients with acute brain injury and varying categories of acute lung injury, defined by PaO2/FiO2. METHOD: Retrospective data were collected from 341 patients with severe acute brain injury admitted to the ICU between 2008 and 2015. These patients experienced a total of 28,644 paired PEEP and ICP observations. Demographic, hemodynamic, physiologic, and ventilator data at the time of the paired PEEP and ICP observations were recorded. RESULTS: In the adjusted analysis, a statistically significant relationship between PEEP and ICP and PEEP and CPP was found only among observations occurring during periods of severe lung injury. For every centimeter H2O increase in PEEP, there was a 0.31 mmHg increase in ICP (p = 0.04; 95 % CI [0.07, 0.54]) and a 0.85 mmHg decrease in CPP (p = 0.02; 95 % CI [-1.48, -0.22]). CONCLUSION: Our results suggest that PEEP can be applied safely in patients with acute brain injury as it does not have a clinically significant effect on ICP or CPP. Further prospective studies are required to assess the safety of applying a lung protective ventilation strategy in brain-injured patients with lung injury.

Acquired copy number alterations in adult acute myeloid leukemia genomes.

Cytogenetic analysis of acute myeloid leukemia (AML) cells has accelerated the identification of genes important for AML pathogenesis. To complement cytogenetic studies and to identify genes altered in AML genomes, we performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult patients with de novo AML using 1.85 million feature SNP arrays. Acquired copy number alterations (CNAs) were confirmed using an ultra-dense array comparative genomic hybridization platform. A total of 201 somatic CNAs were found in the 86 AML genomes (mean, 2.34 CNAs per genome), with French-American-British system M6 and M7 genomes containing the most changes (10-29 CNAs per genome). Twenty-four percent of AML patients with normal cytogenetics had CNA, whereas 40% of patients with an abnormal karyotype had additional CNA detected by SNP array, and several CNA regions were recurrent. The mRNA expression levels of 57 genes were significantly altered in 27 of 50 recurrent CNA regions <5 megabases in size. A total of 8 uniparental disomy (UPD) segments were identified in the 86 genomes; 6 of 8 UPD calls occurred in samples with a normal karyotype. Collectively, 34 of 86 AML genomes (40%) contained alterations not found with cytogenetics, and 98% of these regions contained genes. Of 86 genomes, 43 (50%) had no CNA or UPD at this level of resolution. In this study of 86 adult AML genomes, the use of an unbiased high-resolution genomic screen identified many genes not previously implicated in AML that may be relevant for pathogenesis, along with many known oncogenes and tumor suppressor genes.