Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: An Analysis of 5721 Cases.

OBJECTIVE: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). SUMMARY BACKGROUND DATA: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. RESULTS: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS ( P < 0.0001) and OL ( P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P <0.02). Compared to VATS, RL had lower conversion rate ( P <0.0001), shorter hospital stay ( P <0.0001) and a lower postoperative transfusion rate ( P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. CONCLUSIONS: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: Survival Analysis of 6646 Cases.

OBJECTIVE: The aim of this study was to analyze overall survival (OS) of robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VATS), and open lobectomy (OL) performed by experienced thoracic surgeons across multiple institutions. SUMMARY BACKGROUND DATA: Surgeons have increasingly adopted RL for resection of early-stage lung cancer. Comparative survival data following these approaches is largely from single-institution case series or administrative data sets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. Consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Induction therapy patients were excluded. The propensity-score method of inverse-probability of treatment weighting was used to balance baseline characteristics. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to evaluate association among OS and relevant risk factors. RESULTS: A total of 2789 RL, 2661 VATS, and 1196 OL cases were included. The unadjusted 5-year OS rate was highest for OL (84%) followed by RL (81%) and VATS (74%); P =0.008. Similar trends were also observed after inverse-probability of treatment weighting adjustment (RL 81%; VATS 73%, OL 85%, P =0.001). Multivariable Cox regression analyses revealed that OL and RL were associated with significantly higher OS compared with VATS (OL vs. VATS: hazard ratio=0.64, P <0.001 and RL vs. VATS: hazard ratio=0.79; P =0.007). CONCLUSIONS: Our finding from this large multicenter study suggests that patients undergoing RL and OL have statistically similar OS, while the VATS group was associated with shorter OS. Further studies with longer follow-up are necessary to help evaluate these observations.

CD22L Conjugation to Insulin Attenuates Insulin-Specific B Cell Activation.

Pancreatic islet-reactive B lymphocytes promote Type 1 diabetes (T1D) by presenting an antigen to islet-destructive T cells. Teplizumab, an anti-CD3 monoclonal, delays T1D onset in patients at risk, but additional therapies are needed to prevent the disease entirely. Therefore, bifunctional molecules were designed to selectively inhibit T1D-promoting anti-insulin B cells by conjugating a ligand for the B cell inhibitory receptor CD22 (i.e., CD22L) to insulin, which permit these molecules to concomitantly bind to anti-insulin B cell receptors (BCRs) and CD22. Two prototypes were synthesized: 2:2 insulin-CD22L conjugate on a 4-arm PEG backbone, and 1:1 insulin-CD22L direct conjugate. Transgenic mice (125TgSD) expressing anti-insulin BCRs provided cells for in vitro testing. Cells were cultured with constructs for 3 days, then assessed by flow cytometry. Duplicate wells with anti-CD40 simulated T cell help. A 2-insulin 4-arm PEG control caused robust proliferation and activation-induced CD86 upregulation. Anti-CD40 further boosted these effects. This may indicate that BCR-cross-linking occurs when antigens are tethered by the PEG backbone as soluble insulin alone has no effect. Addition of CD22L via the 2:2 insulin-CD22L conjugate restored B cell properties to that of controls without an additional beneficial effect. In contrast, the 1:1 insulin-CD22L direct conjugate significantly reduced anti-insulin B cell proliferation in the presence of anti-CD40. CD22L alone had no effect, and the constructs did not affect the WT B cells. Thus, multivalent antigen constructs tend to activate anti-insulin B cells, while monomeric antigen-CD22L conjugates reduce B cell activation in response to simulated T cell help and reduce pathogenic B cell numbers without harming normal cells. Therefore, monomeric antigen-CD22L conjugates warrant futher study and may be promising candidates for preclinical trials to prevent T1D without inducing immunodeficiency.

Effort and work-of-breathing parameters strongly correlate with increased resistance in an animal model.

BACKGROUND: Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO). METHODS: RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOBSPIR) or RIP flow (WOBRIP). RESULTS: WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOBSPIR to WOBRIP, a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences. CONCLUSION: EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. IMPACT: EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. There was a strong correlation between spirometry-based WOB versus RIP-based WOB. To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements. Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements.

Lectin Drug Conjugates Targeting High Mannose N-Glycans.

Cancer-associated alterations to glycosylation have been shown to aid cancer development and progression. An increased abundance of high mannose N-glycans has been observed in several cancers. Here, we describe the preparation of lectin drug conjugates (LDCs) that permit toxin delivery to cancer cells presenting high mannose N-glycans. Additionally, we demonstrate that cancer cells presenting low levels of high mannose N-glycans can be rendered sensitive to the LDCs by co-treatment with a type I mannosidase inhibitor. Our findings establish that an increased abundance of high mannose N-glycans in the glycocalyx of cancer cells can be leveraged to enable toxin delivery.

Interest in Hypothetical Preexposure Prophylaxis Against Herpes Simplex Virus: A Cross-Sectional Survey.

ABSTRACT: We surveyed 383 men who have sex with men attending sexual health clinics regarding interest in hypothetical preexposure prophylaxis against herpes simplex virus. Overall interest was 62.5% and was associated with the number of different sexually transmitted infections previously diagnosed (adjusted odds ratio, 1.9; 95% confidence interval, 1.5-2.6) and previous HIV preexposure prophylaxis use (adjusted odds ratio, 2.9; 95% confidence interval, 1.1-8.3).

The Road to Structurally Defined ß-Glucans.

ß-glucans are polymers of glucose that have been isolated from a variety of organisms. Isolated ß-glucans have been used for medical purposes for centuries; however, efforts to define the biological activities of ß-glucans experimentally were initiated in the 1940's. The diversity of structure associated with isolated ß-glucans has impeded said investigations, and efforts to leverage the biological activity of ß-glucans for clinical applications. In recognition of the need for defined ß-glucans that retain the biological activity of isolated ß-glucans, considerable investment has been made to facilitate the synthesis of structurally defined ß-glucans. Here, we review the different approaches that have been applied to prepare ß-glucans. In addition, we summarize the approaches that have been utilized to conjugate ß-glucans to proteins.

Subglottic Post-Extubation Upper Airway Obstruction Is Associated With Long-Term Airway Morbidity in Children.

OBJECTIVES: Post-extubation upper airway obstruction is the most common cause of extubation failure in children, but there are few data regarding long-term morbidity. We aim to describe the frequency of long-term airway sequelae in intubated children and determine the association with post-extubation upper airway obstruction. DESIGN: Retrospective, post hoc analysis of previously identified prospective cohort of children in the pediatric/cardiothoracic ICU at Children's Hospital Los Angeles from July 2012 to April 2015. A single provider blinded to the upper airway obstruction classification reviewed the electronic medical records of all patients in the parent study, before and after the index extubation (extubation during parent study), to identify pre-index and post-index upper airway disease. Primary outcomes were prevalence of newly diagnosed airway anomalies following index extubation. SETTING: Single center, tertiary, 391-bed children's hospital. PATIENTS: From the parent study, 327 children younger than 18 years (intubated for at least 12 hr) were included if they received subsequent care (regardless of specialty) after the index extubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: New airway anomalies were identified in 40 of 327 children (12.2%). Patients labeled with subglottic upper airway obstruction at the index extubation were more likely to be diagnosed with new airway anomalies on subsequent follow-up, receive long-term Otolaryngology follow-up, or receive airway surgery (all p ≤ 0.006). In multivariable modeling, upper airway obstruction as the primary reason for initial intubation (odds ratio, 3.71; CI, 1.50-9.19), reintubation during the index ICU admission (odds ratio, 4.44; CI, 1.67-11.80), pre-index airway anomaly (odds ratio, 3.31; CI, 1.36-8.01), and post-extubation subglottic upper airway obstruction (odds ratio, 3.50; CI, 1.46-8.34) remained independently associated with the diagnosis of new airway anomalies. CONCLUSIONS: Post-extubation subglottic upper airway obstruction is associated with a three-fold greater odds of long-term airway morbidity. These patients may represent an at-risk population that should be monitored closely after leaving the ICU.

Machine Learning to Predict Cardiac Death Within 1 Hour After Terminal Extubation.

OBJECTIVES: Accurate prediction of time to death after withdrawal of life-sustaining therapies may improve counseling for families and help identify candidates for organ donation after cardiac death. The study objectives were to: 1) train a long short-term memory model to predict cardiac death within 1 hour after terminal extubation, 2) calculate the positive predictive value of the model and the number needed to alert among potential organ donors, and 3) examine associations between time to cardiac death and the patient's characteristics and physiologic variables using Cox regression. DESIGN: Retrospective cohort study. SETTING: PICU and cardiothoracic ICU in a tertiary-care academic children's hospital. PATIENTS: Patients 0-21 years old who died after terminal extubation from 2011 to 2018 (n = 237). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median time to death for the cohort was 0.3 hours after terminal extubation (interquartile range, 0.16-1.6 hr); 70% of patients died within 1 hour. The long short-term memory model had an area under the receiver operating characteristic curve of 0.85 and a positive predictive value of 0.81 at a sensitivity of 94% when predicting death within 1 hour of terminal extubation. About 39% of patients who died within 1 hour met organ procurement and transplantation network criteria for liver and kidney donors. The long short-term memory identified 93% of potential organ donors with a number needed to alert of 1.08, meaning that 13 of 14 prepared operating rooms would have yielded a viable organ. A Cox proportional hazard model identified independent predictors of shorter time to death including low Glasgow Coma Score, high Pao2-to-Fio2 ratio, low-pulse oximetry, and low serum bicarbonate. CONCLUSIONS: Our long short-term memory model accurately predicted whether a child will die within 1 hour of terminal extubation and may improve counseling for families. Our model can identify potential candidates for donation after cardiac death while minimizing unnecessarily prepared operating rooms.

Anesthesia for pediatric patients with anti-NMDA receptor encephalitis: A retrospective case series.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor encephalitis is caused by auto-antibodies that target the N-methyl-D-aspartate receptor. Autonomic instability is a hallmark of the disease. The objective of this case series is to examine how anesthesia affects pediatric patients with this disease. METHODS: We performed a retrospective chart review of 28 records in 17 patients who underwent anesthesia. Our primary outcomes were hemodynamic changes during the perioperative period. Heart rate, systolic and diastolic blood pressures, respiratory rate, and oxygen saturation comprise our endpoints. A subgroup of patients, who underwent imaging with anesthesia, was then compared to controls. RESULTS: In anti-N-methyl-D-aspartate receptor encephalitis cases, there were significant percent changes from baseline in heart rate; median = -14.3%, 95% CI (-19.3, -9.0), p < .01 at 30 min and -15.7%, (-21.1, -9.8), p < .01 at 60 min; in systolic blood pressure, -19.4%, (-23.7, -14.8) at 30 min, p < .01, and -14.8%, (-19.7, -9.5) at 60 min, p < .01; in diastolic blood pressure, -41.9%, (-46.9, -36.3), p < .01 at 30 min, and -37.5%, (-43.4, -30.9), p < .01 at 60 min. When compared to controls, there were no significant differences between the two groups across time of anesthesia (baseline to 60 min) in heart rate (p = .24), systolic blood pressure (p = .30), and diastolic blood pressure (p = .11). No patients experienced hemodynamic lability under anesthesia. One patient, with severe symptoms, died within 24 h of anesthesia. CONCLUSION: Although pediatric patients with anti-N-methyl-D-aspartate receptor encephalitis experienced vital sign changes with anesthesia, they were not clinically significant and they behaved similarly to controls. Disease severity may be a risk factor for perioperative complications.

High Interest in Syphilis Pre-exposure and Post-exposure Prophylaxis Among Gay, Bisexual and Other Men Who Have Sex With Men in Vancouver and Toronto.

BACKGROUND: We assessed the acceptability of doxycycline-based syphilis pre-exposure and post-exposure prophylaxis (PrEP/PEP) as well as human immunodeficiency virus (HIV) PrEP/PEP in gay, bisexual, and other men who have sex with men (gbMSM). METHODS: We recruited gbMSM from Toronto and Vancouver sexually transmitted infection (STI) clinics during routine visits from June 2018 to August 2018. We analyzed data using descriptive statistics and constructed multivariable logistic regression models for willingness to use syphilis and HIV PrEP and PEP respectively. RESULTS: Among 424 participants (56.4% Toronto, 43.6% Vancouver), median (interquartile range [IQR]) age was 31.0 years (26.0-39.0 years), 61.7% had completed postsecondary education and 54.4% were white. Median (IQR) number of male partners in the past 6 months was 6.0 (3.0-13.0), and 18.2% had 1 or more prior syphilis diagnosis. 60.1%/44.1% indicated willingness to use syphilis PEP/PrEP; 36.6% were unwilling to use either. Among HIV-negative participants, 74.0% and 75.2% were willing to use HIV PrEP and PEP, respectively. Most participants were familiar with antibiotic resistance (89.0%) and agreed that syphilis rates are rising in Canada (68.2%), but only 55.4% believed they were at risk for syphilis. Agreement with the latter statement was associated with willingness to use syphilis PrEP (adjusted odds ratio [aOR], 1.6; 95% confidence interval [95%CI], 1.0-2.5), as was previous/existing HIV PrEP use (aOR, 2.2; 95% CI, 1.1-4.3) and being "very concerned" about STI acquisition (aOR, 1.9; 95% CI, 1.0-3.4). Odds of being willing to use syphilis PEP were higher in Toronto versus Vancouver (aOR, 2.0; 95% CI, 1.2-3.4) and increased with the number of different STIs previously diagnosed (aOR, 1.4; 95% CI, 1.2,1.7). CONCLUSIONS: There is considerable interest in syphilis PrEP/PEP in gbMSM attending Toronto/Vancouver STI clinics.

Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity.

BACKGROUND: Continuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited. METHODS: This is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50-80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels. RESULTS: Neonates were categorized by postmenstrual age: < 33 (n = 155), 33-36 (n = 192) and > 36 (n = 1031) weeks. From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24-28) n = 2603; 34 (33-35) n = 2501; and 38 (37-39) n = 21,058. The chance of normoxemia (65, 95%-CI 64-67%) was similar across the SpO2 range of 88-95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21-29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18-33%), for infants 33-36 weeks at 97% SpO2 (24, 95%-CI 14-25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17-22%). CONCLUSIONS: The risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.

Impact of Anesthetic and Ventilation Strategies on Invasive Hemodynamic Measurements in Pediatric Heart Transplant Recipients.

BACKGROUND: Care of pediatric heart transplant recipients relies upon serial invasive hemodynamic evaluation, generally performed under the artificial conditions created by anesthesia and supportive ventilation. OBJECTIVES: This study aimed to evaluate the hemodynamic impacts of different anesthetic and ventilatory strategies. METHODS: We compared retrospectively the cardiac index, right- and left-sided filling pressures, and pulmonary and systemic vascular resistances of all clinically well and rejection-free heart transplant recipients catheterized from 2005 through 2017. Effects of spontaneous versus positive pressure ventilation and of sedation versus general anesthesia were tested with generalized linear mixed models for repeated measures using robust sandwich estimators of the covariance matrices. Least squared means showed adjusted mean outcome values, controlled for appropriate confounders. RESULTS: 720 catheterizations from 101 recipients met inclusion criteria. Adjusted cardiac index was 3.14 L/min/m2 (95% CI 3.01-3.67) among spontaneously breathing and 2.71 L/min/m2 (95% CI 2.56-2.86) among ventilated recipients (p < 0.0001). With spontaneous breathing, left filling pressures were lower (9.9 vs 11.0 mmHg, p = 0.030) and systemic vascular resistances were higher (24.0 vs 20.5 Woods units, p < 0.0001). After isolating sedated from anesthetized spontaneously breathing patients, the observed differences in filling pressures and resistances emerged as a function of sedation versus general anesthesia rather than of spontaneous versus positive pressure ventilation. CONCLUSION: In pediatric heart transplant recipients, positive pressure ventilation reduces cardiac output but does not alter filling pressures or vascular resistances. Moderate sedation yields lower left filling pressures and higher systemic vascular resistances than does general anesthesia. Differences are quantitatively small.

Body Habitus and Risk of Mortality in Pediatric Sepsis and Septic Shock: A Retrospective Cohort Study.

OBJECTIVE: To investigate the association between body habitus and mortality in critically ill children with sepsis or septic shock. STUDY DESIGN: This was a retrospective cohort study of prospectively collected data of children admitted to US pediatric intensive care units (PICUs) with a primary or secondary diagnosis of sepsis or septic shock. We separated body habitus into underweight, normal weight, overweight, and obese. Outcomes were mortality (primary), treatment with invasive mechanical ventilation (secondary), and time to PICU discharge for survivors (secondary). Multivariable analyses using mixed-effects logistic regression and shared frailty models clustered by unit and adjusted for confounding variables were used to assess the association between body habitus and outcomes. RESULTS: There were 7038 children with sepsis or septic shock. Mortality was 10.1% (n = 714) and 52.9% (n = 3720) required invasive mechanical ventilation. Body habitus was not associated with mortality after controlling for hospital level effects and confounding variables. Children who were overweight and obese had greater odds of invasive mechanical ventilation (overweight OR 1.23 [95% CI 1.05-1.45], P = .011 and obese OR 1.57 [95% CI 1.37-1.80], P < .001) compared with children of normal weight. In survivors treated with invasive mechanical ventilation, children who were obese had a longer time to PICU discharge than children of normal weight (obese hazard ratio for discharge 0.84 [95% CI, 0.77-0.92], P < .0001). CONCLUSIONS: There was no association between body habitus and mortality in critically ill children with sepsis. Children who were overweight and obese were more likely to receive invasive mechanical ventilation and mechanically ventilated survivors who were obsese had a longer time to PICU discharge.

Catalytic One-Step Deoxytrifluoromethylation of Alcohols.

A new bench-stable trifluoromethylation reagent, phenyl bromodifluoroacetate, converts readily available alcohols to trifluoromethanes in a Cu-catalyzed deoxytrifluoromethylation reaction. This reaction streamlines access to target biologically active molecules, and should be useful for a variety of medicinal, agricultural, and materials chemists.

Evaluating the Practice of Repositioning Endotracheal Tubes in Neonates and Children Based on Radiographic Location.

OBJECTIVES: Chest radiographs are commonly performed in the ICU setting to confirm the position of the endotracheal tube. The purpose of this study was to evaluate the practice and accuracy of repositioning endotracheal tubes in the pediatric population based on chest radiograph. DESIGN: Retrospective review of patient's medical record and chest radiograph. SETTING: Single-institution, academic children's hospital. PATIENTS: PICU and cardiothoracic ICU patients who had repositioning of their endotracheal tube from September 1, 2016, to September 1, 2017. MEASUREMENTS AND MAIN RESULTS: Chest radiograph before and after endotracheal tube repositioning were examined measuring the distance from the endotracheal tube tip to carina. A total of 183 endotracheal tube repositionings were assessed. Twenty-nine percent of endotracheal tube repositionings resulted in a persistently malpositioned endotracheal tube, requiring another intervention. For intended endotracheal tube repositioning of ± 2.0 cm, the actual change measured compared to intended adjustment was a median of 0.7 cm (interquartile range, 0.35-1.1 cm). For intended ± 1.5 cm, the median difference was 0.4 cm (interquartile range, 0.16-0.90 cm). For intended ± 1.0 cm, the median difference was 0.5 cm (interquartile range, 0.20-0.90 cm). For intended ± 0.5 cm, the median difference was 0.3 cm (interquartile range, 0.2-0.88 cm). When the head was malpositioned the difference from intended endotracheal tube repositioning to actual was median 0.70 cm (interquartile range, 0.40-1.1 cm), this was significantly higher than when the head was in a good position CONCLUSIONS:: When repositioning endotracheal tubes based on chest radiograph, there is a significant difference between intended and actual adjustment with great variability. Avoiding very small repositionings (± 0.5 cm) and standardizing head position prior to daily chest radiograph may reduce these errors.

Low-dose dexmedetomidine as an adjuvant to propofol infusion for children in MRI: A double-cohort study.

INTRODUCTION: Propofol is an effective sedative for magnetic resonance imaging. Nevertheless, it may cause hemodynamic and respiratory complications in a dose dependent fashion. We investigated the role of low-dose dexmedetomidine (0.5 µg/kg) as an adjuvant to propofol sedation for children undergoing magnetic resonance imaging. We hypothesized that dexmedetomidine would decrease the propofol dose required, airway complications, and hemodynamic instability. METHODS: We performed a retrospective chart review of patients' age of 1 month to 20 years. Children were divided into 2 groups; group P received only propofol; group D + P received intravenous bolus of dexmedetomidine (0.5 µg/kg) and propofol. RESULTS: We reviewed 172 children in P and 129 in D + P (dexmedetomidine dose, median: 0.50 µg/kg (IQR: 0.45-0.62). An additional dexmedetomidine bolus was given to 17 children for sedation lasting longer than 2 hours. Total propofol dose (µg/kg/min) was significantly higher in group P than D + P; 215.0 (182.6-253.8) vs 147.6 (127.5-180.9); Median Diff = -67.8; 95%CI = -80.6, -54.9; P < .0001. There was no difference in recovery time (minutes); P: 28 (17-39) vs D + P: 27 (18-41); Median Diff = -1; 95%CI = -6.0, 4.0; P = .694. The need for airway support was significantly greater in P compared to D + P; 15/172 vs 3/129; OR = 0.25; 95%CI = 0.07 to 0.90; P = .02 (2-sample proportions test). Mean arterial pressure was significantly lower in P compared to D + P across time over 60 minutes after induction (coef = -0.06, 95%CI = -0.11, -0.02, P = .004). DISCUSSION & CONCLUSION: A low-dose bolus of dexmedetomidine (0.5 µg/kg) used as an adjuvant can decrease the propofol requirement for children undergoing sedation for magnetic resonance imaging. This may decrease the need for airway support and contribute to improved hemodynamic stability without prolonging recovery time.

Intraoperative Hypothermia is Common, but not Associated With Blood Loss or Transfusion in Pediatric Posterior Spinal Fusion.

BACKGROUND: Intraoperative hypothermia may be associated with increased blood loss due to the effects of temperature on clotting but this has not been evaluated in the setting of pediatric posterior spinal fusion (PSF). The purpose of this study was to determine if a correlation exists between intraoperative hypothermia and estimated blood loss (EBL) or transfusion requirements in pediatric patients undergoing PSF. METHODS: A retrospective review of consecutive patients undergoing PSF for scoliosis at a single institution between 6/2004 and 3/2012 was performed. Exclusion criteria were fewer than 10 levels fused, anterior spinal fusion, and patients below 9 years old at time of surgery. Temperature was measured every 15 seconds using esophageal temperature probe. Input variable of hypothermia was analyzed as a binary variable Tmin ≤35°C at any point during anesthesia and as integrated temperature area under the curve (TAUC). RESULTS: A total of 510 with an average age of 14.6 years (range, 9.0 to 24.3 y) met inclusion criteria. Totally, 56% (287/510) had idiopathic scoliosis (IS) and 44% (223/510) were non-IS. Hypothermia (Tmin≤35°C) was experienced by 45% (230/510) of all patients [48% (137/287) of IS; 42% (93/223) of non-IS]. A total of 63% (323/510) of patients were transfused with packed red blood cells (PRBC) [49% (141/287) of IS patients; 82% (182/223) of non-IS patients]. There was no correlation between Tmin≤35°C and transfusion of PRBC in all included patients (P=0.49); (IS patients P=0.45, non-IS patients P=0.61). There was no significant difference in EBL between patients who experienced hypothermia and those who did not (P=0.33; IS patients P=0.21, non-IS patients P=0.87). There was no significant correlation between TAUC and transfusion of PRBC for all patients (P=0.35), IS patients (P=0.26) and non-IS patients (P=0.54) or between TAUC and EBL (P=0.80); (IS patients P=0.57. non-IS patients P=0.62). CONCLUSIONS: There was no significant correlation between intraoperative hypothermia and EBL or transfusion of PRBC in pediatric patients undergoing PSF. LEVEL OF EVIDENCE: Level III.

Comparison of Effort of Breathing for Infants on Nasal Modes of Respiratory Support.

OBJECTIVE: To directly compare effort of breathing between high flow nasal cannula (HFNC), nasal intermittent mechanical ventilation (NIMV), and nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: This was a single center prospective cross-over study for patients <6 months in the cardiothoracic or pediatric intensive care unit receiving nasal noninvasive respiratory support after extubation. We measured effort of breathing using esophageal manometry with pressure-rate product (PRP) on all 3 modes. NIMV synchrony was determined by comparing patient efforts (esophageal manometry) with mechanically delivered breaths (spirometry in ventilator circuit). On NIMV, PRP and synchrony was also measured after adding a nasal clip on 26 patients. RESULTS: Forty-two children were included. Median (IQR) age was 2 (0.5, 4) months. There was no difference in median PRP between HFNC 6 liters per minute, 355 (270,550), NIMV 12/5 cm H2O, 341 (235, 472), and NCPAP 5 cm H2O, 340 (245,506) (P?=?.33). Results were similar regardless of HFNC flow rate or NIMV inspiratory pressure. Median PRP on CPAP of 5 cm H2O prior to extubation 255 (176, 375) was significantly lower than all postextubation values (P??.07)). However, as NIMV synchrony improved (>60%), PRP on NIMV was lower than on HFNC. CONCLUSIONS: For infants, effort of breathing is similar on HFNC, NIMV, and NCPAP after extubation, regardless of flow rate or inspiratory pressure. We speculate that bi-level NIMV may be superior if high levels of synchrony can be achieved.