A Quality Improvement Initiative to Reduce Adverse Effects of Transitions of Anesthesia Care on Postoperative Outcomes: A Retrospective Cohort Study.

BACKGROUND: An intraoperative transfer of care from one anesthesia provider to another, or handover, may result in information loss and contribute to adverse patient outcomes. In 2019 the authors undertook a quality improvement effort to increase the use of a structured intraoperative handover tool incorporated in the electronic medical record. The authors hypothesized that intraoperative handovers of anesthesia care would be associated with adverse patient outcomes, and that increased use of a structured tool would attenuate this effect. METHODS: This study included adult patients undergoing noncardiac surgery of at least 1 h duration performed during the period 2016 to 2021. Cases with a handover were identified if either there was a change of attending anesthesiologist or change of nurse anesthetist or resident for more than 35 min. The primary outcome was the occurrence of a composite of postoperative mortality and major postoperative morbidity. The effect of the intervention was analyzed by examining the quarterly change in odds ratio for the primary outcome for cases with and without a handover. RESULTS: A total of 121,077 cases, 40.4% of which had a handover, were included. After weighting, the composite outcome was statistically associated with handovers (3,517 of 48,986 [7.2%] in handover cases vs. 4,470 of 72,091 [6.2%] in nonhandover cases; odds ratio, 1.08; 95% CI, 1.04 to 1.12). Time series analysis showed a marked increase in usage of the structured tool after the initial intervention. The odds ratio for the composite outcome showed a significant decrease over time after the initial intervention (t = -3.97; P < 0.001), with the slope of the odds ratio versus time curve decreasing from 0.002 (95% CI, 0.001 to 0.004; P = 0.018) to -0.011 (95% CI, -0.01 to -0.018; P < 0.001). CONCLUSIONS: Intraoperative handovers are significantly associated with adverse outcomes even after controlling for multiple confounding variables. Use of a structured handover tool during anesthesia care may attenuate the adverse effect.

Hypoxemia in School-age Children Undergoing One-lung Ventilation: A Retrospective Cohort Study from the Multicenter Perioperative Outcomes Group.

BACKGROUND: Risk factors for hypoxemia in school-age children undergoing one-lung ventilation remain poorly understood. The hypothesis was that certain modifiable and nonmodifiable factors may be associated with increased risk of hypoxemia in school-age children undergoing one-lung ventilation and thoracic surgery. METHODS: The Multicenter Perioperative Outcomes Group database was queried for children 4 to 17 yr of age undergoing one-lung ventilation. Patients undergoing vascular or cardiac procedures were excluded. The original cohort was divided into two cohorts: 4 to 9 and 10 to 17 yr of age inclusive. All records were reviewed electronically for the primary outcome of hypoxemia during one-lung ventilation, which was defined as an oxygen saturation measured by pulse oximetry (Spo2) less than 90% for 3 min or longer continuously, while severe hypoxemia was defined as Spo2 less than 90% for 5 min or longer. Potential modifiable and nonmodifiable risk factors associated with these outcomes were evaluated using separate multivariable least absolute shrinkage and selection operator regression analyses for each cohort. The covariates evaluated included age, extremes of weight, American Society of Anesthesiologists Physical Status of III or higher, duration of one-lung ventilation, preoperative Spo2 less than 98%, approach to one-lung ventilation, right operative side, video-assisted thoracoscopic surgery, lower tidal volume ventilation (defined as tidal volume of 6 ml/kg or less and positive end-expiratory pressure of 4 cm H2O or greater for more than 80% of the duration of one-lung ventilation), and procedure type. RESULTS: The prevalence of hypoxemia in the 4- to 9-yr-old cohort and the 10- to 17-yr-old cohort was 24 of 228 (10.5% [95% CI, 6.5 to 14.5%]) and 76 of 1,012 (7.5% [95% CI, 5.9 to 9.1%]), respectively. The prevalence of severe hypoxemia in both cohorts was 14 of 228 (6.1% [95% CI, 3.0 to 9.3%]) and 47 of 1,012 (4.6% [95% CI, 3.3 to 5.8%]). Initial Spo2 less than 98% was associated with hypoxemia in the 4- to 9-yr-old cohort (odds ratio, 4.20 [95% CI, 1.61 to 6.29]). Initial Spo2 less than 98% (odds ratio, 2.76 [95% CI, 1.69 to 4.48]), extremes of weight (odds ratio, 2.18 [95% CI, 1.29 to 3.61]), and right-sided cases (odds ratio, 2.33 [95% CI, 1.41 to 3.92]) were associated with an increased risk of hypoxemia in the older cohort. Increasing age (1-yr increment; odds ratio, 0.88 [95% CI, 0.80 to 0.97]) was associated with a decreased risk of hypoxemia. CONCLUSIONS: An initial room air oxygen saturation of less than 98% was associated with an increased risk of hypoxemia in all children 4 to 17 yr of age. Extremes of weight, right-sided cases, and decreasing age were associated with an increased risk of hypoxemia in children 10 to 17 yr of age.

Impact of continuous and wireless monitoring of vital signs on clinical outcomes: a propensity-matched observational study of surgical ward patients.

BACKGROUND: Continuous and wireless vital sign monitoring is superior to intermittent monitoring in detecting vital sign abnormalities; however, the impact on clinical outcomes has not been established. METHODS: We performed a propensity-matched analysis of data describing patients admitted to general surgical wards between January 2018 and December 2019 at a single, tertiary medical centre in the USA. The primary outcome was a composite of in-hospital mortality or ICU transfer during hospitalisation. Secondary outcomes were the odds of individual components of the primary outcome, and heart failure, myocardial infarction, acute kidney injury, and rapid response team activations. Data are presented as odds ratios (ORs) with 95% confidence intervals (CIs) and n (%). RESULTS: We initially screened a population of 34,636 patients (mean age 58.3 (Range 18-101) yr, 16,456 (47.5%) women. After propensity matching, intermittent monitoring (n=12 345) was associated with increased risk of a composite of mortality or ICU admission (OR 3.42, 95% CI 3.19-3.67; P<0.001), and heart failure (OR 1.48, 95% CI 1.21-1.81; P<0.001), myocardial infarction (OR 3.87, 95% CI 2.71-5.71; P<0.001), and acute kidney injury (OR 1.32, 95% CI 1.09-1.57; P<0.001) compared with continuous wireless monitoring (n=7955). The odds of rapid response team intervention were similar in both groups (OR 0.86, 95% CI 0.79-1.06; P=0.726). CONCLUSIONS: Patients who received continuous ward monitoring were less likely to die or be admitted to ICU than those who received intermittent monitoring. These findings should be confirmed in prospective randomised trials.

Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a child's neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood.

A novel combined approach to placement of a double lumen endobronchial tube using a video laryngoscope and fiberoptic bronchoscope: a retrospective chart review.

BACKGROUND: The objective of this study was to evaluate a modern combined video laryngoscopy and flexible fiberoptic bronchoscope approach to placement of a double lumen endobronchial tube and further characterize potential strengths and weaknesses of this approach. METHODS: Retrospective chart review was conducted at our single institution, academic medical center, tertiary-care hospital. Patients aged 18 years of age or older were evaluated who underwent thoracic surgery and one-lung ventilation with placement of a double lumen endobronchial tube using a novel combined video laryngoscopy and flexible fiberoptic bronchoscope approach. No interventions were performed. RESULTS: Demographics and induction and intubation documentation were reviewed for 21 patients who underwent thoracic surgery and one-lung ventilation with placement of a double lumen endobronchial tube using a novel combined video laryngoscopy and flexible fiberoptic bronchoscope approach. First pass success using the combined approach was 86% (18/21). The five patients with an anticipated difficult airway had successful double lumen endobronchial tube placement on the first attempt. There were no instances of desaturation during double lumen endobronchial tube placement. No airway complications related to double lumen endobronchial tube placement were recorded. CONCLUSION: Use of a combined approach employing video laryngoscopy and a flexible fiberoptic bronchoscope may represent a reliable alternative approach to placement of double lumen endobronchial tubes.

Agreement between cardiac output estimation with a wireless, wearable pulse decomposition analysis device and continuous thermodilution in post cardiac surgery intensive care unit patients.

PURPOSE: Pulse Decomposition Analysis (PDA) uses integration of the systolic area of a distally transmitted aortic pulse as well as arterial stiffness estimates to compute cardiac output. We sought to assess agreement of cardiac output (CO) estimation between continuous pulmonary artery catheter (PAC) guided thermodilution (CO-CCO) and a wireless, wearable noninvasive device, (Vitalstream, Caretaker Medical, Charlottesville, VA), that utilizes the Pulse Decomposition Analysis (CO-PDA) method in postoperative cardiac surgery patients in the intensive care unit. METHODS: CO-CCO measurements were compared with post processed CO-PDA measurements in prospectively enrolled adult cardiac surgical intensive care unit patients. Uncalibrated CO-PDA values were compared for accuracy with CO-CCO via a Bland-Altman analysis considering repeated measurements and a concordance analysis with a 10% exclusion zone. RESULTS: 259.7 h of monitoring data from 41 patients matching 15,583 data points were analyzed. Mean CO-CCO was 5.55 L/min, while mean values for the CO-PDA were 5.73 L/min (mean of differences +- SD 0.79 ± 1.11 L/min; limits of agreement - 1.43 to 3.01 L/min), with a percentage error of 37.5%. CO-CCO correlation with CO-PDA was moderate (0.54) and concordance was 0.83. CONCLUSION: Compared with the CO-CCO Swan-Ganz, cardiac output measurements obtained using the CO-PDA were not interchangeable when using a 30% threshold. These preliminary results were within the 45% limits for minimally invasive devices, and pending further robust trials, the CO-PDA offers a noninvasive, wireless solution to complement and extend hemodynamic monitoring within and outside the ICU.

Alfentanil Pretreatment for Electroconvulsive Therapy-Associated Hemodynamic Lability: A Prospective Randomized Crossover Trial.

OBJECTIVES: Electroconvulsive therapy (ECT) is frequently associated with significant hemodynamic changes that increase myocardial oxygen demand including significant hypertension poststimulus. This raises concern about the cumulative effect of repetitive stress from ECT. Historically, various agents have been used to blunt this response and reduce hemodynamic fluctuations in these patients with varying degrees of efficacy. We hypothesized that bolus alfentanil administration timed with the ECT stimulus may reduce near-term hypertension and heart rate (HR) increases in patients undergoing ECT. METHODS: A randomized, double-blind, placebo-controlled AB/BA crossover trial of 87 patients 18 years or older with mood disorders was carried out. Patients received a standardized anesthetic regimen including induction with methohexital and succinylcholine and were randomized to receive either 20 µg/kg ideal bodyweight of alfentanil or placebo 60 seconds before the ECT stimulus for the first treatment and then crossed over to the other group for the second treatment. The primary outcome was the within-individual difference in preinduction systolic blood pressure and the first systolic blood pressure after the ECT stimulus. RESULTS: Eighty-seven patients completed the protocol. The primary outcome of increase in systolic blood pressure pre-ECT to post-ECT was 16.9 mm Hg less in the alfentanil group than the placebo group (95% confidence interval, -26.0 to -7.8; P < 0.001). The maximum HR was 6.5 beats per minute lower (95% confidence interval, -12.1 to -0.9; P = 0.024) when patients received alfentanil compared with placebo. CONCLUSIONS: Premedication with alfentanil reduces poststimulus hypertension and increased HR in patients receiving ECT and therefore, may reduce morbidity related to this in susceptible patients.

Agreement between cardiac output estimation by multi-beat analysis of arterial blood pressure waveforms and continuous thermodilution in post cardiac surgery intensive care unit patients.

We sought to assess agreement of cardiac output estimation between continuous pulmonary artery catheter (PAC) guided thermodilution (CO-CTD) and a novel pulse wave analysis (PWA) method that performs an analysis of multiple beats of the arterial blood pressure waveform (CO-MBA) in post-operative cardiac surgery patients. PAC obtained CO-CTD measurements were compared with CO-MBA measurements from the Argos monitor (Retia Medical; Valhalla, NY, USA), in prospectively enrolled adult cardiac surgical intensive care unit patients. Agreement was assessed via Bland-Altman analysis. Subgroup analysis was performed on data segments identified as arrhythmia, or with low CO (less than 5 L/min). 927 hours of monitoring data from 79 patients was analyzed, of which 26 had arrhythmia. Mean CO-CTD was 5.29 ± 1.14 L/min (bias ± precision), whereas mean CO-MBA was 5.36 ± 1.33 L/min, (4.95 ± 0.80 L/min and 5.04 ± 1.07 L/min in the arrhythmia subgroup). Mean of differences was 0.04 ± 1.04 L/min with an error of 38.2%. In the arrhythmia subgroup, mean of differences was 0.14 ± 0.90 L/min with an error of 35.4%. In the low CO subgroup, mean of differences was 0.26 ± 0.89 L/min with an error of 40.4%. In adult patients after cardiac surgery, including those with low cardiac output and arrhythmia CO-MBA is not interchangeable with the continuous thermodilution method via a PAC, when using a 30% error threshold.

Preventing transfusion-associated circulatory overload in acute care settings.

ABSTRACT: Transfusion-associated circulatory overload (TACO) is a potentially life-threatening complication that can occur with the transfusion of any blood component, and accounts for up to 24% of transfusion-associated patient fatalities. This article discusses how to develop evidence-based continuing education and guideline recommendations that will increase nursing staff awareness of TACO and guide nurses in prevention and prompt intervention.

A comparison between liquid group A plasma and thawed group A plasma for massive transfusion activation in trauma patients.

BACKGROUND AND OBJECTIVES: The use of group A thawed 24-h plasma when resuscitating haemorrhagic shock patients has become more common; however, limited data exist on the clinical use of liquid plasma (LP). Our aim is to determine whether LP is of clinical benefit to patients requiring massive transfusion. MATERIALS AND METHODS: The objective of this retrospective study was to detect any difference in 24-h survival between patients receiving liquid or thawed plasma (TP) during their massive transfusion activation. Other objectives were to report any difference in hospital length of stay (LOS), intensive care unit (ICU) LOS and in-hospital survival. Data collected included gender, age, mechanism of injury, Injury Severity Score, Revised Trauma Score and Trauma Injury Severity Score. RESULTS: A total of 178 patients received 1283 units of LP, median 4 and range (1-56), whereas 270 patients received 2031 units of TP, median 5 and range (1-87). The two study groups were comparable in terms of gender, age, mechanism of injury, whole blood, red blood cells, platelets and cryoprecipitate transfused. The use of LP during the massive transfusion activation in traumatically injured patients was not associated with increased 24-h survival compared to when using TP, p = 0.553. CONCLUSION: Our study did not show a difference in 24-h or 30-day survival between the use of LP compared to TP in trauma patients. LP should be considered an alternative to TP in trauma patients requiring immediate plasma resuscitation.

Risk factors for administration of additional reversal following neuromuscular blockade with rocuronium in children: A retrospective case-control study.

BACKGROUND: The prevalence and risk factors for residual neuromuscular blockade in children remain poorly characterized. We hypothesize that specific patient and anesthetic risk factors may be associated with the administration of additional reversal in children following initial reversal of rocuronium with neostigmine. METHODS: Our electronic health record was queried for patients <18 years of age who received rocuronium and reversal with neostigmine from 2017 through 2020. Patients receiving other nondepolarizing neuromuscular blocking drugs were excluded. The outcome of interest was defined as the administration of additional neostigmine or sugammadex following primary reversal with neostigmine. Time between the last dose of rocuronium and initial dose of neostigmine, and the cumulative dose of rocuronium were dichotomized. These were combined with other covariates including age, weight, sex, racial group, procedure type, ASA physical status, >1 rocuronium dose administered during the procedure, initial neostigmine dose <0.05 mg kg-1 , use of train-of-four monitoring, duration of anesthesia, inpatient or outpatient, emergency case, neuromuscular disease, and extremes of weight, to assess possible associations with the primary outcome. RESULTS: During the study period, 101/6373 (1.58%) patients received rocuronium and additional reversal. Dichotomization of time between last dose of rocuronium and neostigmine yielded <28 min since the last dose of rocuronium and cumulative dose of rocuronium >0.45 mg kg-1 hr-1 . These were associated with the administration of additional reversal with an OR 1.52 (95% CI, 1.08-2.35) and OR 1.71 (95% CI, 1.10-2.67), respectively. Other risk factors included an initial neostigmine dose <0.05 mg kg-1 , OR 4.98 (95% CI, 2.84-6.49), and African American race, OR 1.78 (95% CI, 1.07-2.87). CONCLUSION: Risk factors associated with the administration of additional reversal included time <28 min from the last dose of rocuronium to initial dose of neostigmine, cumulative dose of rocuronium >0.45 mg kg-1 hr-1 , initial neostigmine dose <0.05 mg kg-1 , and African American race.

Hypoxemia in Young Children Undergoing One-lung Ventilation: A Retrospective Cohort Study.

BACKGROUND: One-lung ventilation in children remains a specialized practice with low case numbers even at tertiary centers, preventing an assessment of best practices. The authors hypothesized that certain case factors may be associated with a higher risk of intraprocedural hypoxemia in children undergoing thoracic surgery and one-lung ventilation. METHODS: The Multicenter Perioperative Outcomes database and a local quality improvement database were queried for documentation of one-lung ventilation in children 2 months to 3 yr of age inclusive between 2010 and 2020. Patients undergoing vascular or other cardiac procedures were excluded. All records were reviewed electronically for the presence of hypoxemia, oxygen saturation measured by pulse oximetry (Spo2) less than 90% for 3 min or more continuously, and severe hypoxemia, Spo2 less than 90% for 5 min or more continuously during one-lung ventilation. Records were also assessed for hypercarbia, end-tidal CO2 greater than 60 mmHg for 5 min or more or a Paco2 greater than 60 on arterial blood gas. Covariates assessed for association with these outcomes included age, weight, American Society of Anesthesiologists (Schaumburg, Illinois) Physical Status 3 or greater, duration of one-lung ventilation, preoperative Spo2 less than 98%, bronchial blocker versus endobronchial intubation, left operative side, video-assisted thoracoscopic surgery, lower tidal volume ventilation (tidal volume less than or equal to 6 ml/kg plus positive end expiratory pressure greater than or equal to 4 cm H2O for more than 80% of the duration of one-lung ventilation), and type of procedure. RESULTS: Three hundred six cases from 15 institutions were included for analysis. Hypoxemia and severe hypoxemia occurred in 81 of 306 (26%) patients and 56 of 306 (18%), respectively. Hypercarbia occurred in 153 of 306 (50%). Factors associated with lower risk of hypoxemia in multivariable analysis included left operative side (odds ratio, 0.45 [95% CI, 0.251 to 0.78]) and bronchial blocker use (odds ratio, 0.351 [95% CI, 0.177 to 0.67]). Additionally, use of a bronchial blocker was associated with a reduced risk of severe hypoxemia (odds ratio, 0.290 [95% CI, 0.125 to 0.62]). CONCLUSIONS: Use of a bronchial blocker was associated with a lower risk of hypoxemia in young children undergoing one-lung ventilation.

Characteristics of Burn-Injured Children in 117 U.S. PICUs (2009-2017): A Retrospective Virtual Pediatric Systems Database Study.

OBJECTIVES: To describe characteristics and outcomes of children with burn injury treated in U.S. PICUs. DESIGN: Retrospective study of admissions in the Virtual Pediatric Systems, LLC, database from 2009 to 2017. SETTING: One hundred and seventeen PICUs in the United States. PATIENTS: Patients less than 18 years old admitted with an active diagnosis of burn at admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,056 patients were included. They were predominantly male (62.6%) and less than 6 years old (66.7%). Cutaneous burns were recorded in 92.1% of patients, mouth/pharynx burns in 5.8%, inhalation injury in 5.1%, and larynx/trachea/lung burns in 4.5%. Among those with an etiology recorded (n = 861), scald was most common (38.6%), particularly in children less than 2 years old (67.8%). Fire/flame burns were most common (46.6%) in children greater than or equal to 2 years. Multiple organ failure was present in 26.2% of patients. Most patients (89%) were at facilities without American Burn Association pediatric verification. PICU mortality occurred in 4.5% of patients. On multivariable analysis using Pediatric Index of Mortality 2, greater than or equal to 30% total body surface area burned was significantly associated with mortality (odds ratio, 5.40; 95% CI, 2.16-13.51; p = 0.0003). When Pediatric Risk of Mortality III was used, greater than or equal to 30% total body surface area burned (odds ratio, 5.45; 95% CI, 1.95-15.26; p = 0.001) and inhalation injury (odds ratio, 5.39; 95% CI, 1.58-18.42; p = 0.007) were significantly associated with mortality. Among 366 survivors (18.6%) with Pediatric Cerebral Performance Category or Pediatric Overall Performance Category data, 190 (51.9%) had a greater than or equal to 1 point increase in Pediatric Cerebral Performance Category or Pediatric Overall Performance Category disability category and 80 (21.9%) had a new designation of moderate or severe disability, or persistent vegetative state. CONCLUSIONS: Burn-injured patients in U.S. PICUs have a substantial burden of organ failure, morbidity, and mortality. Coordination among specialized facilities may be particularly important in this population, especially for those with higher % total body surface area burned or inhalation injury.

Atrial appendage angiotensin-converting enzyme-2, aging and cardiac surgical patients: a platform for understanding aging-related coronavirus disease-2019 vulnerabilities.

PURPOSE OF REVIEW: Hospitalizations for COVID-19 dramatically increase with age. This is likely because of increases in fragility across biological repair systems and a weakened immune system, including loss of the cardiorenal protective arm of the renin--angiotensin system (RAS), composed of angiotensin-converting enzyme-2 (ACE2)/angiotensin-(1--7) [Ang-(1--7)] and its actions through the Mas receptor. The purpose of this review is to explore how cardiac ACE2 changes with age, cardiac diseases, comorbid conditions and pharmaceutical regimens in order to shed light on a potential hormonal unbalance facilitating SARs-CoV-2 vulnerabilities in older adults. RECENT FINDINGS: Increased ACE2 gene expression has been reported in human hearts with myocardial infarction, cardiac remodeling and heart failure. We also found ACE2 mRNA in atrial appendage tissue from cardiac surgical patients to be positively associated with age, elevated by certain comorbid conditions (e.g. COPD and previous stroke) and increased in conjunction with patients' chronic use of antithrombotic agents and thiazide diuretics but not drugs that block the renin--angiotensin system. SUMMARY: Cardiac ACE2 may have bifunctional roles in COVID-19 as ACE2 not only mediates cellular susceptibility to SARS-CoV-2 infection but also protects the heart via the ACE2/Ang-(1--7) pathway. Linking tissue ACE2 from cardiac surgery patients to their comorbid conditions and medical regimens provides a unique latform to address the influence that altered expression of the ACE2/Ang-(1-7)/Mas receptor axis might have on SARs-CoV-2 vulnerability in older adults.

Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles.

Nanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.

A comparison between leukocyte reduced low titer whole blood vs non-leukocyte reduced low titer whole blood for massive transfusion activation.

BACKGROUND: Hemorrhagic shock is the leading cause of survivable death in trauma patients and recent literature has focused on resuscitation strategies including transfusing low-titer group O whole blood (LTOWB). Debate remains regarding whether leukocyte reduced (LR) whole blood is of clinical benefit or detriment to patients requiring massive transfusion. This study compares survival outcomes between LR-LTOWB and non-LR LTOWB. STUDY DESIGN AND METHODS: The objective of this prospective, observational study was to detect any difference in 24-hour survival between patients receiving LR-LTOWB and non-LR LTOWB during their massive transfusion activation. Secondary objectives were to report any difference in ICU LOS, ventilation days, in-hospital survival, and hospital LOS. Data collected included patient sex, age, mechanism of injury, Injury Severity Score (ISS), Trauma Injury Severity Score (TRISS), cause of death, and number of LTOWB transfused. RESULTS: A total of 167 patients received 271 LTOWB transfusions. There were 97 patients that received 168 units of LR-LTOWB while 70 patients received 103 units of non-LR LTOWB. The two study groups were comparable in terms of age, sex, ISS, TRISS, and the number of LTOWB transfused. The use of LR LTOWB during the initial massive transfusion activation in traumatically injured patients was not associated with increased 24-hour survival compared to when using non-LR LTOWB. No transfusion associated adverse events were reported. CONCLUSIONS: The administration of either LR or non-LR LTOWB was not associated with >24 hours survival in patients presenting with massive hemorrhage. The high cost and the rapid decline in platelet count of LR whole blood may be a consideration.

Influence of membrane cholesterol on monocyte chemotaxis.

Cholesterol content influences several important physiological functions due to its effect on membrane receptors. In this work, we tested the hypothesis that cellular cholesterol alters chemotactic response of monocytes to Monocyte Chemoattractant Protein-1 (MCP-1) due to their effect on the receptor, CCR2. We used Methyl-ß-cyclodextrin (MßCD) to alter the baseline cholesterol in human monocytic cell line THP-1, and evaluated their chemotactic response to MCP-1. Compared to untreated cells, cholesterol enrichment increased the number of monocytes transmigrated in response to MCP-1 while depletion had opposite effect. Using imaging flow cytometry, we established that these differences were due to alterations in expression levels, but not the surface distribution, of CCR2.

Cholesterol Regulates Monocyte Rolling through CD44 Distribution.

Cholesterol is an important risk factor of atherosclerosis, due to its active uptake by monocytes/macrophages. Monocyte recruitment from flowing blood to atherosclerotic foci is the key first step in the development of atherosclerosis. Cholesterol content alters cell membrane stiffness, and lateral lipid and protein diffusion. We hypothesized that cholesterol content will modulate the recruitment of monocytes to inflamed endothelial surface by altering the dynamics of adhesion receptors. We depleted or enriched the cellular cholesterol levels using methyl-ß-cyclodextran in freshly isolated human monocytes. We investigated the effect of these changes on the mechanics of monocyte rolling on E-selectin surfaces at 1 dyn/cm2 in microchannels. Using imaging flow cytometry and atomic force microscopy, we characterized the distribution of lipid rafts and the E-selectin counterreceptor CD44 on the monocyte surface. We observed that lower levels of cholesterol resulted in the uniform, CD44-mediated rolling of monocytes on the E-selectin-coated surfaces. We also observed that cells depleted of cholesterol had higher membrane fluidity, and more uniform distribution of CD44 counterreceptor, which resulted in smooth motion of the cells compared to cells enriched with cholesterol. This work demonstrates that cholesterol can modulate monocyte adhesion by regulating the receptor mobility, and our results provide insights into the biophysical regulation of inflammation for the better understanding of diseases like atherosclerosis and hypercholesterolemia.