Development of a predictive model for risk stratification of acute kidney injury in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients' preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71-0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.

Best Practice Alerts Informed by Inpatient Opioid Intake to Reduce Opioid Prescribing after Surgery (PRIOR): A Cluster Randomized Multiple Crossover Trial.

BACKGROUND: Overprescription of opioids after surgery remains common. Residual and unnecessarily prescribed opioids can provide a reservoir for nonmedical use. This study therefore tested the hypothesis that a decision-support tool embedded in electronic health records guides clinicians to prescribe fewer opioids at discharge after inpatient surgery. METHODS: This study included 21,689 surgical inpatient discharges in a cluster randomized multiple crossover trial from July 2020 to June 2021 in four Colorado hospitals. Hospital-level clusters were randomized to alternating 8-week periods during which an electronic decision-support tool recommended tailored discharge opioid prescriptions based on previous inpatient opioid intake. During active alert periods, the alert was displayed to clinicians when the proposed opioid prescription exceeded recommended amounts. No alerts were displayed during inactive periods. Carryover effects were mitigated by including 4-week washout periods. The primary outcome was oral morphine milligram equivalents prescribed at discharge. Secondary outcomes included combination opioid and nonopioid prescriptions and additional opioid prescriptions until day 28 after discharge. A vigorous state-wide opioid education and awareness campaign was in place during the trial. RESULTS: The total postdischarge opioid prescription was a median [quartile 1, quartile 3] of 75 [0, 225] oral morphine milligram equivalents among 11,003 patients discharged when the alerts were active and 100 [0, 225] morphine milligram equivalents in 10,686 patients when the alerts were inactive, with an estimated ratio of geometric means of 0.95 (95% CI, 0.80 to 1.13; P = 0.586). The alert was displayed in 28% (3,074 of 11,003) of the discharges during the active alert period. There was no relationship between the alert and prescribed opioid and nonopioid combination medications or additional opioid prescriptions written after discharge. CONCLUSIONS: A decision-support tool incorporated into electronic medical records did not reduce discharge opioid prescribing for postoperative patients in the context of vigorous opioid education and awareness efforts. Opioid prescribing alerts might yet be valuable in other contexts.(Anesthesiology 2023; 139:186-96).

Alveolar-Capillary Barrier Protection In Vitro: Lung Cell Type-Specific Effects and Molecular Mechanisms Induced by 1α, 25-Dihydroxyvitamin D3.

Low serum levels of 1α, 25-dihydroxyvitamin D3 (VD3) are associated with a higher mortality in trauma patients with sepsis or ARDS. However, the molecular mechanisms behind this observation are not yet understood. VD3 is known to stimulate lung maturity, alveolar type II cell differentiation, or pulmonary surfactant synthesis and guides epithelial defense during infection. In this study, we investigated the impact of VD3 on the alveolar-capillary barrier in a co-culture model of alveolar epithelial cells and microvascular endothelial cells respectively in the individual cell types. After stimulation with bacterial LPS (lipopolysaccharide), gene expression of inflammatory cytokines, surfactant proteins, transport proteins, antimicrobial peptide, and doublecortin-like kinase 1 (DCLK1) were analyzed by real-time PCR, while corresponding proteins were evaluated by ELISA, immune-fluorescence, or Western blot. The effect of VD3 on the intracellular protein composition in H441 cells was analyzed by quantitative liquid chromatography-mass spectrometry-based proteomics. VD3 effectively protected the alveolar-capillary barrier against LPS treatment, as indicated by TEER measurement and morphological assessment. VD3 did not inhibit the IL-6 secretion by H441 and OEC but restricted the diffusion of IL-6 to the epithelial compartment. Further, VD3 could significantly suppress the surfactant protein A expression induced in the co-culture system by LPS treatment. VD3 induced high levels of the antimicrobial peptide LL-37, which counteracted effects by LPS and strengthened the barrier. Quantitative proteomics identified VD3-dependent protein abundance changes ranging from constitutional extracellular matrix components and surfactant-associated proteins to immune-regulatory molecules. DCLK1, as a newly described target molecule for VD3, was prominently stimulated by VD3 (10 nM) and seems to influence the alveolar-epithelial cell barrier and regeneration.

Case series: Immune checkpoint inhibitor-induced transverse myelitis.

Introduction: Increasing implementation of the highly efficacious immune checkpoint inhibitors (ICIs) has raised awareness of their various complications in the form of immune-related adverse events (irAEs). Transverse myelitis following ICIs is thought to be a rare but serious neurologic irAE and knowledge is limited about this distinct clinical entity. Cases: We describe four patients across three tertiary centers in Australia with ICI-induced transverse myelitis. Three patients had a diagnosis of stage III-IV melanoma treated with nivolumab and one patient had stage IV non-small cell lung cancer treated with pembrolizumab. All patients had longitudinally extensive transverse myelitis on magnetic resonance imaging (MRI) spine and clinical presentation was accompanied by inflammatory cerebrospinal fluid (CSF) findings. Half of our cohort had received spinal radiotherapy, with the areas of transverse myelitis extending beyond the level of previous radiation field. Inflammatory changes on neuroimaging did not extend to the brain parenchyma or caudal nerve roots, except for one case involving the conus medullaris. All patients received high dose glucocorticoids as first-line therapy, however the majority relapsed or had a refractory state (3/4) despite this, requiring escalation of their immunomodulation, with either induction intravenous immunoglobulin (IVIg) or plasmapheresis. Patients in our cohort who relapsed had a poorer outcome with more severe disability and reduced functional independence following resolution of their myelitis. Two patients had no progression of their malignancy and two patients had malignancy progression. Of the three patients who survived, two had resolution of their neurological symptoms and one remained symptomatic. Conclusion: We propose that prompt intensive immunomodulation is favored for patients with ICI-transverse myelitis in an attempt to reduce associated significant morbidity and mortality. Furthermore, there is a significant risk of relapse following cessation of immunomodulatory therapy. We suggest one treatment approach of IVMP and induction IVIg for all patients presenting with ICI-induced transverse myelitis based on such findings. With the increasing use of ICIs across oncology, further studies are required to explore this neurological phenomenon in greater detail to help establish management consensus guidelines.

A Randomized Pilot Study Assessing if SEDLine Monitoring During Induction of Surgical Patients is Associated With Reduced Dosage of Administered Induction Agents.

Background. Intubations, especially in emergent settings, carry a high risk of hemodynamic instability with potentially catastrophic outcomes. Weight-based dosing of induction drugs can be inappropriately high for elective or emergent intubations and lead to hemodynamic instability. We hypothesized that monitoring the patient state index of SEDLine monitors (Masimo, Irvine, CA) would decrease the dose of induction drugs in the operating room during elective intubations.Methods. In this randomized study, SEDLine monitoring was provided to the intervention group but not to the control group during the induction of anesthesia in the operating room. Anesthesia providers in the intervention group were advised to titrate induction drugs to a Patient State Index of <50 before proceeding with intubation. The primary outcome was the induction dose of propofol and etomidate per kilogram normalized to propofol dose equivalents. Secondary outcomes included supplemental doses of ketamine, midazolam, fentanyl, phenylephrine, and ephedrine per kg, time from induction to intubation, administration of additional propofol or vasopressors after induction, mean arterial pressure ≥ or <65 mmHg, and lowest mean arterial pressure post-induction.Results. We found no significant difference in propofol equivalents between groups (P = .41). Using a SEDLine decreased the odds that a patient would require vasopressors during induction (odds ratio of .39 [95% confidence interval, .15-.98]).Conclusion. SEDLine monitoring during induction did not decrease dosing of the induction drugs etomidate and propofol but decreased the odds of receiving vasopressors. Further studies are warranted to assess the utility of processed electroencephalography in emergent intubations outside of the operating room.

Incidence of Postoperative Cognitive Dysfunction Following Inhalational vs Total Intravenous General Anesthesia: A Systematic Review and Meta-Analysis.

Postoperative cognitive dysfunction (POCD) has been increasingly recognized as a contributor to postoperative complications. A consensus-working group recommended that POCD should be distinguished between delayed cognitive recovery, ie, evaluations up to 30 days postoperative, and neurocognitive disorder, ie, assessments performed between 30 days and 12 months after surgery. Additionally, the choice of the anesthetic, either inhalational or total intravenous anesthesia (TIVA) and its effect on the incidence of POCD, has become a focus of research. Our primary objective was to search the literature and conduct a meta-analysis to verify whether the choice of general anesthesia may impact the incidence of POCD in the first 30 days postoperatively. As a secondary objective, a systematic review of the literature was conducted to estimate the effects of the anesthetic on POCD between 30 days and 12 months postoperative. For the primary objective, an initial review of 1913 articles yielded ten studies with a total of 3390 individuals. For the secondary objective, four studies with a total of 480 patients were selected. In the first 30 days postoperative, the odds-ratio for POCD in TIVA group was 0.46 (95% CI = 0.26-0.81; p = 0.01), compared to the inhalational group. TIVA was associated with a lower incidence of POCD in the first 30 days postoperatively. Regarding the secondary objective, due to the small number of selected articles and its high heterogeneity, a metanalysis was not conducted. Given the heterogeneity of criteria for POCD, future prospective studies with more robust designs should be performed to fully address this question.

Association between alcohol use disorder and hospital outcomes in colectomy patients - A retrospective cohort study.

STUDY OBJECTIVE: In the United States, alcohol use disorder adversely affects 5.6% of all adults. Excessive alcohol consumption adversely affects organ functions critical for adaptation to stress induced by surgery. Colorectal resection is one of the most common major surgeries in patients at risk for alcohol use disorder. The objective of this study was to assess the impact of alcohol use disorder on hospital outcomes after colectomy using a population-based discharge database. SETTING: Population-based discharge database. PATIENTS: The Premier Healthcare Database was queried for the 603,730 adult patients who underwent colectomy from 2016 to 2019. INTERVENTIONS: None. MEASUREMENTS: Multiple logistic regressions estimated the associations between in-hospital mortality, length of stay, and hospitalization cost with alcohol use disorder as the primary predictor, adjusting for other substance use disorders, psychotic disorders, depression, other Elixhauser comorbidities, age, payor, race, gender, non-elective surgery, and other unbalanced variables. MAIN RESULTS: A discharge code for alcohol use disorder was identified in 2.9% of colectomy patients and the overall in-hospital mortality rate in all sampled colectomy patients was 1.4%. Alcohol use disorder was associated with a significantly increased risk of in-hospital mortality after adjusting for other factors (AOR 1.36, 95% CI 1.24-1.48, p < 0.0001). Alcohol use disorder was also significantly associated with long length of stay (AOR 1.45, 95% CI 1.39-1.52, p < 0.0001) and high hospitalization costs (AOR 1.63, 95% CI 1.56-1.70, p < 0.0001). CONCLUSIONS: Alcohol use disorder is associated with an increased risk of in-hospital mortality in patients undergoing colectomy, one of the most common major surgeries. Future research should examine if enhanced efforts to identify patients with alcohol use disorder could enable anesthesiologists to provide worthwhile perioperative interventions for this high-risk population.

Robotic infant surgery with 3 mm instruments: a study in piglets of less than 10 kg body weight.

No data exist concerning the appication of a new robotic system with 3 mm instruments (Senhance®, Transenterix) in infants and small children. Therefore, the aim of this study was to test the system for its feasibility, performance and safety of robotic pediatric abdominal and thoracic surgery in piglets simulating infants with a body weight lower than 10 kg. 34 procedures (from explorative laparoscopy to thoracoscopic esophageal repair) were performed in 12 piglets with a median age of 23 (interquartile range: 12-28) days and a median body weight of 6.9 (6.1-7.3) kg. The Senhance® robotic system was used with 3 mm instruments, a 10 mm 3D 0° or 30° videoscope and advanced energy devices, the setup consisted of the master console and three separate arms. The amount, size, and position of the applied ports, their distance as well as the distance between the three operator arms of the robot, external and internal collisions, and complications of the procedures were recorded and analyzed. We were able to perform all planned surgical procedures with 3 mm robotic instruments in piglets with a median body weight of less than 7 kg. We encountered two non-robot associated complications (bleeding from the inferior caval and hepatic vein) which led to termination of the live procedures. Technical limitations were the reaction time and speed of robotic camera movement with eye tracking, the excessive bending of the 3 mm instruments and intermittent need of re-calibration of the fulcrum point. Robotic newborn and infant surgery appears technically feasible with the Senhance® system. Software adjustments for camera movement and sensitivity of the fulcrum point calibration algorithm to adjust for the increased compliance of the abdominal wall of infants, therefore reducing the bending of the instruments, need to be implemented by the manufacturer as a result of our study. To further evaluate the Senhance® system, prospective trials comparing it to open, laparoscopic and other robotic systems are needed.

Year in Review 2020: Noteworthy Literature in Cardiothoracic Critical Care.

This year will be forever marked by the drastic changes COVID-19 wrought on our personal and professional lives. New roles and challenges in critical care have forced us to be constantly nimble and flexible in how we approach medicine. The strain of these challenges is apparent throughout the health care community and our society as a whole. Despite this adversity, 2020 will also be remembered for fantastic advances in research. This article is a collection of influential and exciting studies published in 2020 encompassing a broad swath of critical care with a focus on cardiothoracic critical care. Themes include examinations of early extracorporeal membrane oxygenation support for out-of-hospital cardiac arrest patients, the impact of sedation and other risk factors on perioperative mortality, a novel fluid resuscitation strategy following cardiac surgery, and advances in the fields of heart and lung transplantation as well as how they were affected by COVID-19. Given that many cardiothoracic intensivists were redeployed to the care of SARS-CoV-2 patients, we also discuss important advances in therapeutics for the virus.

Medical treatment of polymeric cerebral granulomatous reactions following endovascular procedures.

BACKGROUND: Endovascular procedures are standard of care for an increasing range of cerebrovascular diseases. Many endovascular devices contain plastic and are coated with a hydrophilic polymer which has been rarely described to embolize, resulting in distal granulomatous inflammatory lesions within the vascular territory. METHODS: We reviewed three cases of cerebral granulomatous reactions that occurred after endovascular intervention for internal carotid aneurysms. The patient procedure details, presentation, relevant investigations, and treatment course are described. We also provide a literature review on endovascular granulomatous reactions. RESULTS: These three cases represent the largest biopsy proven series of cerebral granulomatosis following endovascular intervention. We highlight the variable clinical presentation, with two of the three cases having an unusually delayed onset of up to 4 years following the intervention. We show the characteristic histological findings of granulomatous lesions with foreign body material consistent with a type IV reaction, radiological abnormalities of enhancing lesions within the vascular territory of the intervention, and the requirement of prolonged immunosuppression for maintenance of clinical remission, with two of the three patients requiring a corticosteroid sparing agent. In comparison with the available literature, in addition to hydrophilic gel polymer, we discuss that plastic from the lining of the envoy catheter may be a source of embolic material. We also discuss the recommendations of the Food and Drug Administration and the implementation of novel biomaterials for the prevention of these reactions in the future. CONCLUSIONS: There is a need for increased awareness of this severe complication of cerebral endovascular procedures and further longitudinal studies of its prevalence, optimal management and preventative measures.

Transesophageal echocardiography for perioperative management in thoracic surgery.

PURPOSE OF REVIEW: Perioperative transesophageal echocardiography (TEE) is most often employed during cardiac surgery. This review will summarize some of the recent findings relevant to TEE utilization during thoracic surgical procedures. RECENT FINDINGS: Hemodynamic monitoring is a key component of goal-directed fluid therapy, which is also becoming more common for management of thoracic surgical procedures. Although usually not required for the anesthetic management of common thoracic surgeries, TEE is frequently used during lung transplantation and pulmonary thromboendarterectomy. Few clinical studies support current practice patterns, and most recommendations are based on expert opinion. SUMMARY: Currently, routine use of TEE in thoracic surgery is often limited to specific high-risk patients and/or procedures. As in other perioperative settings, TEE may be utilized to elucidate the reasons for acute hemodynamic instability without apparent cause. Contraindications to TEE apply and have to be taken into consideration before performing a TEE on a thoracic surgical patient.

Characteristics and Outcomes of Mechanically Ventilated COVID-19 Patients-An Observational Cohort Study.

BACKGROUND: The United States currently has more confirmed cases of COVID-19 than any other country in the world. Given the variability in COVID-19 testing and prevention capability, identifying factors associated with mortality in patients requiring mechanical ventilation is critical. This study aimed to identify which demographics, comorbidities, markers of disease progression, and interventions are associated with 30-day mortality in COVID-19 patients requiring mechanical ventilation. METHODS: Adult patients with a confirmed diagnosis of COVID-19 admitted to one of the health system's intensive care units and requiring mechanical ventilation between March 9, 2020 and April 1, 2020, were included in this observational cohort study. We used Chi-Square and Mann-Whitney U tests to compare patient characteristics between deceased and living patients and multiple logistic regression to assess the association between independent variables and the likelihood of 30-day mortality. RESULTS: We included 85 patients, of which 20 died (23.5%) within 30 days of the first hospital admission. In the univariate analysis, deceased patients were more likely ≥60 years of age (p < 0.001), non-Hispanic (p = 0.026), and diagnosed with a solid malignant tumor (p = 0.003). Insurance status also differed between survivors and non-survivors (p = 0.019). Age ≥60 and malignancy had a 9.5-fold (95% confidence interval 1.4-62.3, p = 0.020) and 5.8-fold higher odds ratio (95% confidence interval 1.2-28.4, p = 0.032) for 30-day mortality after adjusted analysis using multivariable logistic regression, while other independent variables were no longer significant. CONCLUSIONS: In our observational cohort study of 85 mechanically ventilated COVID-19 patients, age, and a diagnosis of a solid malignant tumor were associated with 30-day mortality. Our findings validate concerns for the survival of elderly and cancer patients in the face of the COVID-19 pandemic in the United States, where testing capabilities and preventative measures have been inconsistent. Preventative efforts geared to patients at risk for intensive care unit mortality from COVID-19 should be explored.

Association between procalcitonin levels and duration of mechanical ventilation in COVID-19 patients.

BACKGROUND: Patients diagnosed with COVID-19 frequently require mechanical ventilation. Knowledge of laboratory tests associated with the prolonged need for mechanical ventilation may guide resource allocation. We hypothesized that an elevated plasma procalcitonin level (>0.1 ng/ml) would be associated with the duration of invasive mechanical ventilation. METHODS: Patients diagnosed with COVID-19, who were admitted to any of our health system's hospitals between March 9th-April 20th, 2020 and required invasive mechanical ventilation, were eligible for this observational cohort study. Demographics, comorbidities, components of the Sequential Organ Failure Assessment score, and procalcitonin levels on admission were obtained from the electronic health record. The primary outcome was the duration of mechanical ventilation; secondary outcomes included 28-day mortality and time to intubation. Outcomes were assessed within the first 28 days of admission. Baseline demographics and comorbidities were summarized by descriptive statistics. Univariate comparisons were made using Pearson's chi-square test for binary outcomes and Mann-Whitney U test for continuous outcomes. A multiple linear regression was fitted to assess the association between procalcitonin levels and the duration of mechanical ventilation. RESULTS: Patients with an initial procalcitonin level >0.1 ng/ml required a significantly longer duration of mechanical ventilation than patients with a level of ≤0.1 ng/ml (p = 0.021) in the univariate analysis. There was no significant difference in 28-day mortality or time to intubation between the two groups. After adjusted analysis using multivariable linear regression, the duration of mechanical ventilation was, on average, 5.6 (p = 0.016) days longer in patients with an initial procalcitonin level >0.1 ng/ml. CONCLUSION: In this cohort of 93 mechanically ventilated COVID-19 patients, we found an association between an initial plasma procalcitonin level >0.1 ng/ml and the duration of mechanical ventilation. These findings may help to identify patients at risk for prolonged mechanical ventilation upon admission.

Current Neurologic Assessment and Neuroprotective Strategies in Cardiac Anesthesia: A Survey to the Membership of the Society of Cardiovascular Anesthesiologists.

BACKGROUND: Neurologic injury and cognitive disorder after cardiac surgery are associated with morbidity and mortality. Variability in the application of neuroprotective strategies likely exists during cardiac surgery. The Society of Cardiovascular Anesthesiologists (SCA) conducted a survey among its members on common perioperative neuroprotective strategies: assessment of aortic atheromatous burden, management of intraoperative blood pressure, and use of cerebral oximetry. METHODS: A 15-item survey was developed by 3 members of the SCA Continuous Practice Improvement - Cerebral Protection Working Group. The questionnaire was then circulated among all working group members, adapted, and tested for face validity. On March 26, 2018, the survey was sent to members of the SCA via e-mail using the Research Electronic Data Capture system. Responses were recorded until April 16, 2018. RESULTS: Of the 3645 surveys e-mailed, 526 members responded (14.4%). Most responders worked in academic institutions (58.3%), followed by private practices (38.7%). Epiaortic ultrasound for the assessment of aortic atheromatous burden was most commonly utilized at the surgeon's request (46.5%). Cerebral oximetry was most commonly used in patients with increased perioperative risk of cerebral injury (41.4%). Epiaortic ultrasound (1.9%) and cerebral oximetry (5.2%) were rarely part of a standardized monitoring approach. A majority of respondents (52.0%) reported no standardized management strategies for neuroprotection during cardiac surgery at their institution. A total of 55.3% stated that no standardized institutional guidelines were in place for managing a patient's blood pressure intraoperatively or during cardiopulmonary bypass. When asked about patients at risk for postoperative cerebral injury, 41.3% targeted a blood pressure goal >65 mmHg during cardiopulmonary bypass. The majority of responders (60.4%) who had access to institutional rates of postoperative stroke/cerebral injury had standard neuroprotective strategies in place. CONCLUSIONS: Our data indicate that approximately half of the respondents to this SCA survey do not use standardized guidelines/standard operating procedures for perioperative cerebral protection. The lack of standardized neuroprotective strategies during cardiac surgery may impact postoperative neurologic outcomes. Further investigations are warranted and should assess the association of standardized neuroprotective approaches and postoperative neurological outcomes.

Neostigmine Versus Sugammadex for Reversal of Neuromuscular Blockade and Effects on Reintubation for Respiratory Failure or Newly Initiated Noninvasive Ventilation: An Interrupted Time Series Design.

BACKGROUND: Pulmonary complications related to residual neuromuscular blockade lead to morbidity and mortality. Using an interrupted time series design, we tested whether proportions of reintubation for respiratory failure or new noninvasive ventilation were changed after a system-wide transition of the standard reversal agent from neostigmine to sugammadex. METHODS: Adult patients undergoing a procedure with general anesthesia that included pharmacologic reversal of neuromuscular blockade and admission ≥1 night were eligible. Groups were determined by date of surgery: August 15, 2015 to May 10, 2016 (presugammadex), and August 15, 2016 to May 11, 2017 (postsugammadex). The period from May 11, 2016 to August 14, 2016 marked the institutional transition (washout/wash-in) from neostigmine to sugammadex. The primary outcome was defined as a composite of reintubation for respiratory failure or new noninvasive ventilation. Event proportions were parsed into 10-day intervals in each cohort, and trend lines were fitted. Segmented logistic regression models appropriate for an interrupted time series design and adjusting for potential confounders were utilized to evaluate the immediate effect of the implementation of sugammadex and on the difference between preintervention and postintervention slopes of the outcomes. Models containing all parameters (full) and only significant parameters (parsimonious) were fitted and are reported. RESULTS: Of 13,031 screened patients, 7316 patients were included. The composite respiratory outcome occurred in 6.1% of the presugammadex group and 4.2% of the postsugammadex group. Adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the composite respiratory outcome were 0.795 (95% CI, 0.523-1.208) for the immediate effect of intervention, 0.986 (95% CI, 0.959-1.013) for the difference between preintervention and postintervention slopes in the full model, and 0.667 (95% CI, 0.536-0.830) for the immediate effect of the intervention in the parsimonious model. CONCLUSIONS: The system-wide transition of the standard pharmacologic reversal agent from neostigmine to sugammadex was associated with a reduction in the odds of the composite respiratory outcome. This observation is supported by nonsignificant within-group time trends and a significant reduction in intercept/level from presugammadex to postsugammadex in a parsimonious logistic regression model adjusting for covariates.

PICU mortality of children with cancer admitted to pediatric intensive care unit a systematic review and meta-analysis.

BACKGROUND: Outcomes for children diagnosed with cancer have improved dramatically over the past 20 years. However, although 40% of pediatric cancer patients require at least one intensive care admission throughout their disease course, PICU outcomes and resource utilization by this population have not been rigorously studied in this specific group. METHODS: Using a systematic strategy, we searched Medline, Embase, and CINAHL databases for articles describing PICU mortality of pediatric cancer patients admitted to PICU. Two investigators independently applied eligibility criteria, assessed data quality, and extracted data. We pooled PICU mortality estimates using random-effects models and examined mortality trends over time using meta-regression models. RESULTS: Out of 1218 identified manuscripts, 31 studies were included covering 16,853 PICU admissions with the majority being retrospective in nature. Overall pooled weighted mortality was 27.8% (95% confidence interval (CI), 23.7-31.9%). Mortality decreased slightly over time when post-operative patients were excluded. The use of mechanical ventilation (odds ratio (OR): 18.49 [95% CI 13.79-24.78], p < 0.001), inotropic support (OR: 14.05 [95% CI 9.16-21.57], p < 0.001), or continuous renal replacement therapy (OR: 3.24 [95% CI 1.31-8.04], p = 0.01) was significantly associated with PICU mortality. CONCLUSIONS: PICU mortality rates of pediatric cancer patients are far higher when compared to current mortality rates of the general PICU population. PICU mortality has remained relatively unchanged over the past decades, a slight decrease was only seen when post-operative patients were excluded. This compared infavorably with the improved mortality seen in adults with cancer admitted to ICU, where research-led improvements have led to the paradigm of unlimited, aggressive ICU management without any limitations on resuscitations status, for a time-limited trial.

Ultrasound-guided airway blocks using a curvilinear probe.

We describe a novel technique of real-time ultrasound-guided superior laryngeal nerve and translaryngeal blocks in 4 patients with anticipated difficult airways. All patients had altered neck anatomy, and 1 had a prior unsuccessful awake fiberoptic bronchoscopic intubation. For block performance, an 11-mm broadband curved array transducer with a scanning frequency between 8 and 5 MHz (Sonosite, Bothell, WA) was used for anatomical structure identification, needle guidance toward each superior laryngeal nerve and through the cricothyroid membrane, and deposition of local anesthetic in the appropriate location. This was followed by successful awake fiberoptic bronchoscopic endotracheal intubation in all cases.

Rationale and design of Short-Term EXenatide therapy in Acute ischaemic Stroke (STEXAS): a randomised, open-label, parallel-group study.

INTRODUCTION: Both hyperglycaemia and hypoglycaemia in acute ischaemic stroke (AIS) are associated with increased infarct size and worse functional outcomes. Thus, therapies that can maintain normoglycaemia during stroke are clinically important. Glucagon-like peptide 1 (GLP-1) analogues, including exenatide, are routinely used in the treatment of hyperglycaemia in type 2 diabetes, but data on the usefulness of this class of agents in the management of elevated glucose levels in AIS are limited. Owing to their glucose-dependent mechanism of action, GLP-1 analogues are associated with a low risk of hypoglycaemia, which may give them an advantage over intensive insulin therapy in the acute management of hyperglycaemia in this setting. METHODS AND ANALYSIS: The Short-Term EXenatide therapy in Acute ischaemic Stroke study is a randomised, open-label, parallel-group pilot study designed to investigate the efficacy of exenatide at lowering blood glucose levels in patients with hyperglycaemia with AIS. A total of 30 patients presenting with AIS and blood glucose levels >10 mmol/L will be randomised to receive the standard therapy (intravenous insulin) or intravenous exenatide for up to 72 h. Outcomes including blood glucose levels within the target range (5-10 mmol/L), the incidence of hypoglycaemia and the feasibility of administering intravenous exenatide in this patient population will be assessed. A follow-up visit at 3 months will facilitate evaluation of neurological outcomes post-stroke. ETHICS AND DISSEMINATION: This study has been approved by the local Institutional Review Board (Northern Sydney Local Health District Human Research Ethics Committee). The study results will be communicated via presentations at scientific conferences and through publication in peer-reviewed journals. CONCLUSIONS: As GLP-1 analogues require elevated glucose levels to exert their insulin potentiating activity, the use of exenatide in the management of hyperglycaemia in AIS may reduce the incidence of hypoglycaemia, thereby conferring a benefit in morbidity and mortality for patients in the long term. TRIAL REGISTRATION NUMBER: ACTRN12614001189617.

Peptide Recognition of Cholesterol in Fluid Phospholipid Bilayers.

N-Acetyl-LWYIKC-amide, a cholesterol recognition/interaction amino acid consensus (CRAC) peptide, has been found capable of recognizing an exchangeable form of cholesterol in liquid-disordered (l(d)) bilayers derived from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). In sharp contrast, such recognition is barely detectable in analogous cholesterol-rich, liquid-ordered (l0) bilayers. These findings represent the first evidence for a peptide favoring a sterol as a nearest-neighbor in fluid bilayers. They also reveal that such recognition can be strongly dependent on the degree of compactness of the membrane.