A Prospective Multicenter Comparison of Trauma and Injury Severity Score, American Society of Anesthesiologists Physical Status, and National Surgical Quality Improvement Program Calculator's Ability to Predict Operative Trauma Outcomes.

BACKGROUND: Trauma outcome prediction models have traditionally relied upon patient injury and physiologic data (eg, Trauma and Injury Severity Score [TRISS]) without accounting for comorbidities. We sought to prospectively evaluate the role of the American Society of Anesthesiologists physical status (ASA-PS) score and the National Surgical Quality Improvement Program Surgical Risk-Calculator (NSQIP-SRC), which are measurements of comorbidities, in the prediction of trauma outcomes, hypothesizing that they will improve the predictive ability for mortality, hospital length of stay (LOS), and complications compared to TRISS alone in trauma patients undergoing surgery within 24 hours. METHODS: A prospective, observational multicenter study (9/2018-2/2020) of trauma patients ≥18 years undergoing operation within 24 hours of admission was performed. Multiple logistic regression was used to create models predicting mortality utilizing the variables within TRISS, ASA-PS, and NSQIP-SRC, respectively. Linear regression was used to create models predicting LOS and negative binomial regression to create models predicting complications. RESULTS: From 4 level I trauma centers, 1213 patients were included. The Brier Score for each model predicting mortality was found to improve accuracy in the following order: 0.0370 for ASA-PS, 0.0355 for NSQIP-SRC, 0.0301 for TRISS, 0.0291 for TRISS+ASA-PS, and 0.0234 for TRISS+NSQIP-SRC. However, when comparing TRISS alone to TRISS+ASA-PS (P = .082) and TRISS+NSQIP-SRC (P = .394), there was no significant improvement in mortality prediction. NSQIP-SRC more accurately predicted both LOS and complications compared to TRISS and ASA-PS. CONCLUSIONS: TRISS predicts mortality better than ASA-PS and NSQIP-SRC in trauma patients undergoing surgery within 24 hours. The TRISS mortality predictive ability is not improved when combined with ASA-PS or NSQIP-SRC. However, NSQIP-SRC was the most accurate predictor of LOS and complications.

Systems Engineering Approach to Modeling and Analysis of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by airflow limitation. This study develops a systems engineering framework for representing important mechanistic details of COPD in a model of the cardiorespiratory system. In this model, we present the cardiorespiratory system as an integrated biological control system responsible for regulating breathing. Four engineering control system components are considered: sensor, controller, actuator, and the process itself. Knowledge of human anatomy and physiology is used to develop appropriate mechanistic mathematical models for each component. Following a systematic analysis of the computational model, we identify three physiological parameters associated with reproducing clinical manifestations of COPD: changes in the forced expiratory volume, lung volumes, and pulmonary hypertension. We quantify the changes in these parameters (airway resistance, lung elastance, and pulmonary resistance) as the ones that result in a systemic response that is diagnostic of COPD. A multivariate analysis of the simulation results reveals that the changes in airway resistance have a broad impact on the human cardiorespiratory system and that the pulmonary circuit is stressed beyond normal under hypoxic environments in most COPD patients.

Closed-loop modeling of central and intrinsic cardiac nervous system circuits underlying cardiovascular control.

The baroreflex is a multi-input, multi-output control physiological system that regulates blood pressure by modulating nerve activity between the brainstem and the heart. Existing computational models of the baroreflex do not explictly incorporate the intrinsic cardiac nervous system (ICN), which mediates central control of the heart function. We developed a computational model of closed-loop cardiovascular control by integrating a network representation of the ICN within central control reflex circuits. We examined central and local contributions to the control of heart rate, ventricular functions, and respiratory sinus arrhythmia (RSA). Our simulations match the experimentally observed relationship between RSA and lung tidal volume. Our simulations predicted the relative contributions of the sensory and the motor neuron pathways to the experimentally observed changes in the heart rate. Our closed-loop cardiovascular control model is primed for evaluating bioelectronic interventions to treat heart failure and renormalize cardiovascular physiology.

Comparison of National Surgical Quality Improvement Program Surgical Risk Calculator and Trauma and Injury Severity Score Risk Assessment Tools in Predicting Outcomes in High-Risk Operative Trauma Patients.

BACKGROUND: The Trauma and Injury Severity Score (TRISS) uses anatomic/physiologic variables to predict outcomes. The National Surgical Quality Improvement Program Surgical Risk Calculator (NSQIP-SRC) includes functional status and comorbidities. It is unclear which of these tools is superior for high-risk trauma patients (American Society of Anesthesiologists Physical Status (ASA-PS) class IV or V). This study compares risk prediction of TRISS and NSQIP-SRC for mortality, length of stay (LOS), and complications for high-risk operative trauma patients. METHODS: This is a prospective study of high-risk (ASA-PS IV or V) trauma patients (≥18 years-old) undergoing surgery at 4 trauma centers. We compared TRISS vs NSQIP-SRC vs NSQIP-SRC + TRISS for ability to predict mortality, LOS, and complications using linear, logistic, and negative binomial regression. RESULTS: Of 284 patients, 48 (16.9%) died. The median LOS was 16 days and number of complications was 1. TRISS + NSQIP-SRC best predicted mortality (AUROC: .877 vs .723 vs .843, P = .0018) and number of complications (pseudo-R2/median error (ME) 5.26%/1.15 vs 3.39%/1.33 vs 2.07%/1.41, P < .001) compared to NSQIP-SRC or TRISS, but there was no difference between TRISS + NSQIP-SRC and NSQIP-SRC with LOS prediction (P = .43). DISCUSSION: For high-risk operative trauma patients, TRISS + NSQIP-SRC performed better at predicting mortality and number of complications compared to NSQIP-SRC or TRISS alone but similar to NSQIP-SRC alone for LOS. Thus, future risk prediction and comparisons across trauma centers for high-risk operative trauma patients should include a combination of anatomic/physiologic data, comorbidities, and functional status.

Elucidating the Mechanisms of Dynamic and Robust Control of the Liver Homeostatic Renewal Process: Cell Network Modeling and Analysis.

Recent experimental investigations of liver homeostatic renewal have identified high replication capacity hepatocyte populations as the primary maintainers of liver mass. However, the molecular and cellular processes controlling liver homeostatic renewal remain unknown. To address this problem, we developed and analyzed a mathematical model describing cellular network interactions underlying liver homeostatic renewal. Model simulation results demonstrate that without feedback control, basic homeostatic renewal is not robust to disruptions, leading to tissue loss under persistent/repetitive insults. Consequently, we extended our basic model to incorporate putative regulatory interactions and investigated how such interactions may confer robustness on the homeostatic renewal process. We utilized a Design of Experiments approach to identify the combination of feedback interactions that yields a cell network model of homeostatic renewal capable of maintaining liver mass robustly during persistent/repetitive injury. Simulations of this robust model indicate that repeated injury destabilizes liver homeostasis within several months, which differs from epidemiological observations of a much slower decay of liver function occurring over several years. To address this discrepancy, we extended the model to include feedback control by liver nonparenchymal cells. Simulations and analysis of the final multicellular feedback control network suggest that achieving robust liver homeostatic renewal requires intrinsic stability in a hepatocellular network combined with feedback control by nonparenchymal cells.

Comparison of National Surgical Quality Improvement Program Surgical Risk Calculator, Trauma and Injury Severity Score, and American Society of Anesthesiologists Physical Status to predict operative trauma mortality in elderly patients.

BACKGROUND: The Trauma and Injury Severity Score (TRISS) uses anatomical and physiologic variables to predict mortality. Elderly (65 years or older) trauma patients have increased mortality and morbidity for a given TRISS, in part because of functional status and comorbidities. These factors are incorporated into the American Society of Anesthesiologists Physical Status (ASA-PS) and National Surgical Quality Improvement Program Surgical Risk Calculator (NSQIP-SRC). We hypothesized scoring tools using comorbidities and functional status to be superior at predicting mortality, hospital length of stay (LOS), and complications in elderly trauma patients undergoing operation. METHODS: Four level I trauma centers prospectively collected data on elderly trauma patients undergoing surgery within 24 hours of admission. Using logistic regression, five scoring models were compared: ASA-PS, NSQIP-SRC, TRISS, TRISS-ASA-PS, and TRISS-NSQIP-SRC.Brier scores and area under the receiver operator characteristics curve were calculated to compare mortality prediction. Adjusted R2 and root mean squared error were used to compare LOS and predictive ability for number of complications. RESULTS: From 122 subjects, 9 (7.4%) died, and the average LOS was 12.9 days (range, 1-110 days). National Surgical Quality Improvement Program Surgical Risk Calculator was superior to ASA-PS and TRISS at predicting mortality (area under the receiver operator characteristics curve, 0.978 vs. 0.768 vs. 0.903; p = 0.007). Furthermore, NSQIP-SRC was more accurate predicting LOS (R2, 25.9% vs. 13.3% vs. 20.5%) and complications (R2, 34.0% vs. 22.6% vs. 29.4%) compared with TRISS and ASA-PS. Adding TRISS to NSQIP-SRC improved predictive ability compared with NSQIP-SRC alone for complications (R2, 35.5% vs. 34.0%; p = 0.046). However, adding ASA-PS or TRISS to NSQIP-SRC did not improve the predictive ability for mortality or LOS. CONCLUSION: The NSQIP-SRC, which includes comorbidities and functional status, had superior ability to predict mortality, LOS, and complications compared with TRISS alone in elderly trauma patients undergoing surgery. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Rational Design of Hydrogel Networks with Dynamic Mechanical Properties to Mimic Matrix Remodeling.

Engineered hydrogels are increasingly used as extracellular matrix (ECM) surrogates for probing cell function in response to ECM remodeling events related to injury or disease (e.g., degradation followed by deposition/crosslinking). Inspired by these events, this work establishes an approach for pseudo-reversible mechanical property modulation in synthetic hydrogels by integrating orthogonal, enzymatically triggered crosslink degradation, and light-triggered photopolymerization stiffening. Hydrogels are formed by a photo-initiated thiol-ene reaction between multiarm polyethylene glycol and a dually enzymatically degradable peptide linker, which incorporates a thrombin-degradable sequence for triggered softening and a matrix metalloproteinase (MMP)-degradable sequence for cell-driven remodeling. Hydrogels are stiffened by photopolymerization using a flexible, MMP-degradable polymer-peptide conjugate and multiarm macromers, increasing the synthetic matrix crosslink density while retaining degradability. Integration of these tools enables sequential softening and stiffening inspired by matrix remodeling events within loose connective tissues (Young's modulus (E) ≈5 to 1.5 to 6 kPa with >3x ΔE). The cytocompatibility and utility of this approach is examined with breast cancer cells, where cell proliferation shows a dependence on the timing of triggered softening. This work provides innovative tools for 3D dynamic property modulation that are synthetically accessible and cell compatible.

Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial.

PURPOSE: Etomidate and ketamine are hemodynamically stable induction agents often used to sedate critically ill patients during emergency endotracheal intubation. In 2015, quality improvement data from our hospital suggested a survival benefit at Day 7 from avoidance of etomidate in critically ill patients during emergency intubation. In this clinical trial, we hypothesized that randomization to ketamine instead of etomidate would be associated with Day 7 survival after emergency endotracheal intubation. METHODS: A prospective, randomized, open-label, parallel assignment, single-center clinical trial performed by an anesthesiology-based Airway Team under emergent circumstances at one high-volume medical center in the United States. 801 critically ill patients requiring emergency intubation were randomly assigned 1:1 by computer-generated, pre-randomized sealed envelopes to receive etomidate (0.2-0.3 mg/kg, n = 400) or ketamine (1-2 mg/kg, n = 401) for sedation prior to intubation. The pre-specified primary endpoint of the trial was Day 7 survival. Secondary endpoints included Day 28 survival. RESULTS: Of the 801 enrolled patients, 396 were analyzed in the etomidate arm, and 395 in the ketamine arm. Day 7 survival was significantly lower in the etomidate arm than in the ketamine arm (77.3% versus 85.1%, difference - 7.8, 95% confidence interval - 13, - 2.4, p = 0.005). Day 28 survival rates for the two groups were not significantly different (etomidate 64.1%, ketamine 66.8%, difference - 2.7, 95% confidence interval - 9.3, 3.9, p = 0.294). CONCLUSION: While the primary outcome of Day 7 survival was greater in patients randomized to ketamine, there was no significant difference in survival by Day 28.

A Spatial Model of Hepatic Calcium Signaling and Glucose Metabolism Under Autonomic Control Reveals Functional Consequences of Varying Liver Innervation Patterns Across Species.

Rapid breakdown of hepatic glycogen stores into glucose plays an important role during intense physical exercise to maintain systemic euglycemia. Hepatic glycogenolysis is governed by several different liver-intrinsic and systemic factors such as hepatic zonation, circulating catecholamines, hepatocellular calcium signaling, hepatic neuroanatomy, and the central nervous system (CNS). Of the factors regulating hepatic glycogenolysis, the extent of lobular innervation varies significantly between humans and rodents. While rodents display very few autonomic nerve terminals in the liver, nearly every hepatic layer in the human liver receives neural input. In the present study, we developed a multi-scale, multi-organ model of hepatic metabolism incorporating liver zonation, lobular scale calcium signaling, hepatic innervation, and direct and peripheral organ-mediated communication between the liver and the CNS. We evaluated the effect of each of these governing factors on the total hepatic glucose output and zonal glycogenolytic patterns within liver lobules during simulated physical exercise. Our simulations revealed that direct neuronal stimulation of the liver and an increase in circulating catecholamines increases hepatic glucose output mediated by mobilization of intracellular calcium stores and lobular scale calcium waves. Comparing simulated glycogenolysis between human-like and rodent-like hepatic innervation patterns (extensive vs. minimal) suggested that propagation of calcium transients across liver lobules acts as a compensatory mechanism to improve hepatic glucose output in sparsely innervated livers. Interestingly, our simulations suggested that catecholamine-driven glycogenolysis is reduced under portal hypertension. However, increased innervation coupled with strong intercellular communication can improve the total hepatic glucose output under portal hypertension. In summary, our modeling and simulation study reveals a complex interplay of intercellular and multi-organ interactions that can lead to differing calcium dynamics and spatial distributions of glycogenolysis at the lobular scale in the liver.

Blood preservation techniques in complex spine surgery: Illustrative case and review of therapeutic options.

BACKGROUND: Complex spine surgery predisposes patients to substantial levels of blood loss, which can increase the risk of surgical morbidity and mortality. CASE DESCRIPTION: A 29-year-old achondroplastic male required thoracolumbar deformity correction. However, he refused potential allogeneic blood transfusions for religious reasons. He, therefore, underwent pre-operative autologous blood donation and consented to the use of the intraoperative cell salvage device. Immediately prior to the incision, he underwent acute normovolemic hemodilution. Throughout the case, we additionally utilized meticulous hemostasis. Postoperatively, he was supplemented with iron and erythropoietin and recovered well. When he required a revision procedure 3 months later, similar strategies were successfully employed. CONCLUSION: Numerous strategies exist pre-operatively, intraoperatively, and post-operatively to optimize blood loss management for patients who refuse blood transfusions but warrant major spinal deformity surgery.

Low-dose aspirin for preventing intrauterine growth restriction and pre-eclampsia in sickle cell pregnancy (PIPSICKLE): a randomised controlled trial (study protocol).

INTRODUCTION: Pregnancy in sickle cell disease is fraught with many complications including pre-eclampsia (PE) and intrauterine growth restriction (IUGR). Previously, we found an abnormality in prostacyclin-thromboxane ratio in sickle cell pregnant women, a situation that is also found in non-sickle pregnancies with PE and unexplained IUGR. Low-dose aspirin (LDA) has been shown to reduce the incidence of PE and IUGR in high-risk women by reducing the vasoconstrictor thromboxane while sparing prostacyclin, in effect 'correcting' the ratio. It has been found to be safe for use in pregnancy but has not been tested in sickle cell pregnancy. We hypothesise that LDA will reduce the incidence of IUGR and PE in pregnant haemoglobin SS (HbSS) and haemoglobin SC (HbSC) women. METHODS AND ANALYSIS: This is a multisite, double blind, randomised controlled trial, comparing a daily dose of 100 mg aspirin to placebo, from 12 to 16 weeks' gestation until 36 weeks, in Lagos state, Nigeria. Four hundred and seventy-six eligible pregnant HbSS and HbSC women will be recruited consecutively, randomly assigned to either group and followed from recruitment until delivery. The primary outcome will be the incidence of birth weight below 10th centile for gestational age on INTERGROWTH 21 birth weight charts, or incidence of miscarriage or perinatal death. Secondary outcomes will include PE, maternal death, preterm delivery, perinatal death, number of crises, need for blood transfusion and complications such as infections and placental abruption. Analysis will be by intention to treat and the main treatment effects will be quantified by relative risk with 95% CI, at a 5% significance level. ETHICAL APPROVAL: Ethical approval has been granted by the Health Research and Ethics committees of the recruiting hospitals and the National Health Research and Ethics Committee. Study findings will be presented at conferences and published appropriately. TRAIL REGISTRATION NUMBER: PACTR202001787519553; Pre-results.

A Positive Cocaine Urine Toxicology Test and the Effect on Intraoperative Hemodynamics Under General Anesthesia.

BACKGROUND: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. METHODS: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. RESULTS: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (ß coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (ß coefficient = 0.2%, P < .001, CI, 4-3). CONCLUSIONS: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Modeling the Effect of Amino Acids and Copper on Monoclonal Antibody Productivity and Glycosylation: A Modular Approach.

In manufacturing monoclonal antibodies (mAbs), it is crucial to be able to predict how process conditions and supplements affect productivity and quality attributes, especially glycosylation. Supplemental inputs, such as amino acids and trace metals in the media, are reported to affect cell metabolism and glycosylation; quantifying their effects is essential for effective process development. We aim to present and validate, through a commercially relevant cell culture process, a technique for modeling such effects efficiently. While existing models can predict mAb production or glycosylation dynamics under specific process configurations, adapting them to new processes remains challenging, because it involves modifying the model structure and often requires some mechanistic understanding. Here, a modular modeling technique for adapting an existing model for a fed-batch Chinese hamster ovary (CHO) cell culture process without structural modifications or mechanistic insight is presented. Instead, data is used, obtained from designed experimental perturbations in media supplementation, to train and validate a supplemental input effect model, which is used to "patch" the existing model. The combined model can be used for model-based process development to improve productivity and to meet product quality targets more efficiently. The methodology and analysis are generally applicable to other CHO cell lines and cell types.

An Exceedingly Rare Presentation of Severe Folate Deficiency-Induced Non-Immune Hemolytic Anemia.

Macrocytic anemia is usually associated with vitamin B12 or folate deficiency. However, folate deficiency was rarely reported as a cause of hemolytic anemia. We present a case of a young man with a history of alcohol abuse who initially presented with an acute on chronic abdominal pain and was found to have jaundice and scleral icterus. His liver enzymes were unremarkable, and his abdominal imaging did not reveal any acute pathology. However, he was found to have a severe non-immune hemolytic anemia secondary to folate deficiency.

Media supplementation for targeted manipulation of monoclonal antibody galactosylation and fucosylation.

Monoclonal antibodies are critically important biologics as the largest class of molecules used to treat cancers, rheumatoid arthritis, and other chronic diseases. Antibody glycosylation is a critical quality attribute that has ramifications for patient safety and physiological efficacy-one that can be modified by such factors as media formulation and process conditions during production. Using a design-of-experiments approach, we examined the effect of 2-F-peracetyl fucose (2FP), uridine, and galactose on cell growth and metabolism, titer, and gene expression of key glycosylation-related proteins, and report how the glycoform distribution changed from Days 4 to 7 in a batch process used for IgG1 production from Chinese hamster ovary cells. We observed major glycosylation changes upon supplement addition, where the addition of 2FP decreased antibody fucosylation by up to 48%, galactose addition increased galactosylation by up to 21%, and uridine addition decreased fucosylation and increased galactosylation by 6% and 2%, respectively. Despite having major effects on glycosylation, neither galactose nor 2FP significantly affected cell culture growth, metabolism, or titer. Uridine improved peak cell densities by 23% but also reduced titer by ∼30%. The supplements caused significant changes in gene expression by Day 4 of the cultures where 2FP addition significantly reduced fucosyltransferase 8 and nucleotide sugar transporter gene expression (by ∼2-fold), and uridine addition significantly increased expression of UDP-GlcNAcT (SLC35A3) and B4GALT1-6 genes (by 1.5-3-fold). These gene expression data alongside glycosylation, metabolic, and growth data improve our understanding of the cellular mechanisms affected by media supplementation and suggest approaches for modifying antibody glycosylation in antibody production processes.

Investigating the Effects of Brainstem Neuronal Adaptation on Cardiovascular Homeostasis.

Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. Recent single-cell analyses within the brain revealed that individual neurons within and across brain nuclei exhibit distinct transcriptional states contributing to neuronal function. Such transcriptional heterogeneity complicates the task of understanding how neurons within and across brain nuclei organize and function to process multiple inputs and coordinate cardiovascular functions within the larger context of the baroreceptor reflex. However, prior analysis of brainstem neurons revealed that single-neuron transcriptional heterogeneity reflects an adaptive response to synaptic inputs and that neurons organize into distinct subtypes with respect to synaptic inputs received. Based on these results, we hypothesize that adaptation of neuronal subtypes support robust biological function through graded cellular responses. We test this hypothesis by examining the functional impact of neuronal adaptation on parasympathetic activity within the context of short-term baroreceptor reflex regulation. In this work, we extend existing quantitative closed-loop models of the baroreceptor reflex by incorporating into the model distinct input-driven neuronal subtypes and neuroanatomical groups that modulate parasympathetic activity. We then use this extended model to investigate, via simulation, the functional role of neuronal adaptation under conditions of health and systolic heart failure. Simulation results suggest that parasympathetic activity can be modulated appropriately by the coordination of distinct neuronal subtypes to maintain normal cardiovascular functions under systolic heart failure conditions. Moreover, differing degrees of adaptation of these neuronal subtypes contribute to cardiovascular behaviors corresponding to distinct clinical phenotypes of heart failure, such as exercise intolerance. Further, our results suggest that an imbalance between sympathetic and parasympathetic activity regulating ventricular contractility contributes to exercise intolerance in systolic heart failure patients, and restoring this balance can improve the short-term cardiovascular performance of these patients.

Diurnal Patterns of Gene Expression in the Dorsal Vagal Complex and the Central Nucleus of the Amygdala - Non-rhythm-generating Brain Regions.

Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications for the design of gene expression studies as well as for the potential effects of xenobiotics on these regions that regulate autonomic and emotional states.

Sugammadex versus neostigmine for reversal of rocuronium-induced neuromuscular blockade: A randomized, double-blinded study of thoracic surgical patients evaluating hypoxic episodes in the early postoperative period.

STUDY OBJECTIVE: This objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus neostigmine results in a decreased number of hypoxic episodes in the early postoperative period in patients undergoing thoracic surgery with single lung ventilation. DESIGN: Single-center, randomized, double-blind, two-arm clinical trial. SETTING: Operating room and postanesthesia care unit. PATIENTS: 92 subjects aged ≥18, American Society of Anesthesiologists physical status II-IV, and undergoing a thoracic operation necessitating single lung ventilation. INTERVENTIONS: Subjects received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 8 µg/kg glycopyrrolate for reversal of moderate neuromuscular blockade. MEASUREMENTS: For the first 90 min postoperatively, all episodes of hypoxia were recorded. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch® SX) and the train of four (TOF) was recorded at 2, 5, 10, and 15 min after administration of the neuromuscular reversal agent. MAIN RESULTS: Subjects who received neostigmine had a median of 1 episode (interquartile range IQR: 0-2.2) of hypoxia versus subjects who received sugammadex who had a median of 0 episodes (IQR: 0-1) (p = 0.009). The mean time to recovery of TOF ≥ 0.9 was significantly faster with sugammadex at 10 min (95% confidence interval CI: 5-15) compared with neostigmine at 40 min (95% CI: 15-53) (p < 0.001). CONCLUSIONS: In thoracic surgical patients necessitating single lung ventilation, sugammadex provides faster reversal of moderate neuromuscular blockade and results in a decreased number of postoperative hypoxic episodes compared with neostigmine.