Migratory Neural Crest Cells Phagocytose Dead Cells in the Developing Nervous System.

During neural tube closure and spinal cord development, many cells die in both the central and peripheral nervous systems (CNS and PNS, respectively). However, myeloid-derived professional phagocytes have not yet colonized the trunk region during early neurogenesis. How apoptotic cells are removed from this region during these stages remains largely unknown. Using live imaging in zebrafish, we demonstrate that neural crest cells (NCCs) respond rapidly to dying cells and phagocytose cellular debris around the neural tube. Additionally, NCCs have the ability to enter the CNS through motor exit point transition zones and clear debris in the spinal cord. Surprisingly, NCCs phagocytosis mechanistically resembles macrophage phagocytosis and their recruitment toward cellular debris is mediated by interleukin-1ß. Taken together, our results reveal a role for NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes.

Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults.

BACKGROUND: Whether video laryngoscopy as compared with direct laryngoscopy increases the likelihood of successful tracheal intubation on the first attempt among critically ill adults is uncertain. METHODS: In a multicenter, randomized trial conducted at 17 emergency departments and intensive care units (ICUs), we randomly assigned critically ill adults undergoing tracheal intubation to the video-laryngoscope group or the direct-laryngoscope group. The primary outcome was successful intubation on the first attempt. The secondary outcome was the occurrence of severe complications during intubation; severe complications were defined as severe hypoxemia, severe hypotension, new or increased vasopressor use, cardiac arrest, or death. RESULTS: The trial was stopped for efficacy at the time of the single preplanned interim analysis. Among 1417 patients who were included in the final analysis (91.5% of whom underwent intubation that was performed by an emergency medicine resident or a critical care fellow), successful intubation on the first attempt occurred in 600 of the 705 patients (85.1%) in the video-laryngoscope group and in 504 of the 712 patients (70.8%) in the direct-laryngoscope group (absolute risk difference, 14.3 percentage points; 95% confidence interval [CI], 9.9 to 18.7; P<0.001). A total of 151 patients (21.4%) in the video-laryngoscope group and 149 patients (20.9%) in the direct-laryngoscope group had a severe complication during intubation (absolute risk difference, 0.5 percentage points; 95% CI, -3.9 to 4.9). Safety outcomes, including esophageal intubation, injury to the teeth, and aspiration, were similar in the two groups. CONCLUSIONS: Among critically ill adults undergoing tracheal intubation in an emergency department or ICU, the use of a video laryngoscope resulted in a higher incidence of successful intubation on the first attempt than the use of a direct laryngoscope. (Funded by the U.S. Department of Defense; DEVICE ClinicalTrials.gov number, NCT05239195.).

Association of Geographic Distance and Hospital Characteristics With Use of Interhospital Transfer by Air: A Multicenter Retrospective Study.

OBJECTIVE: Interhospital transfer by air (IHTA) represents the majority of helicopter air ambulance transports in the United States, but the evaluation of what factors are associated with utilization has been limited. We aimed to assess the association of geographic distance and hospital characteristics (including patient volume) with the use of IHTA. METHODS: This was a multicenter, retrospective study of helicopter flight request data from 2018 provided by a convenience sample of 4 critical care transport medicine programs in 3 US census regions. Nonfederal referring hospitals located in the home state of the associated critical care transport medicine program and within 100 miles of the primary receiving facility in the region were included if complete data were available. We fit a Poisson principal component regression model incorporating geographic distance, the number of emergency department visits, the number of hospital discharges, case mix index, the number of intensive care unit beds, and the number of general beds and tested the association of the variables with helicopter emergency medical services utilization. RESULTS: A total of 106 referring hospitals were analyzed, 21 of which were hospitals identified as having a consistent request pattern. Using the hospitals with a consistent referral pattern, geographic distance had a significant positive association with flight request volume. Other variables, including emergency department visit volume, were not associated. Overall, the included variables offered poor explanatory power for the observed variation between referring facilities in the use of IHTA (r2 = 0.09). Predicted flights based on the principal component regression model for all referring hospitals suggested the majority of referring hospitals used multiple flight programs. CONCLUSION: Geographic distance is associated with the use of IHTA. Unexpectedly, most basic hospital characteristics are not associated with the use of IHTA, and the degree of variation between referring facilities that is explained by patient volume is limited. The evaluation of nonhospital factors, such as the density and availability of critical care or advanced life support ground emergency medical services resources, is needed.

Glutamate Signaling via the AMPAR Subunit GluR4 Regulates Oligodendrocyte Progenitor Cell Migration in the Developing Spinal Cord.

Oligodendrocyte progenitor cells (OPCs) are specified from discrete precursor populations during gliogenesis and migrate extensively from their origins, ultimately distributing throughout the brain and spinal cord during early development. Subsequently, a subset of OPCs differentiates into mature oligodendrocytes, which myelinate axons. This process is necessary for efficient neuronal signaling and organism survival. Previous studies have identified several factors that influence OPC development, including excitatory glutamatergic synapses that form between neurons and OPCs during myelination. However, little is known about how glutamate signaling affects OPC migration before myelination. In this study, we use in vivo, time-lapse imaging in zebrafish in conjunction with genetic and pharmacological perturbation to investigate OPC migration and myelination when the GluR4A ionotropic glutamate receptor subunit is disrupted. In our studies, we observed that gria4a mutant embryos and larvae displayed abnormal OPC migration and altered dorsoventral distribution in the spinal cord. Genetic mosaic analysis confirmed that these effects were cell-autonomous, and we identified that voltage-gated calcium channels were downstream of glutamate receptor signaling in OPCs and could rescue the migration and myelination defects we observed when glutamate signaling was perturbed. These results offer new insights into the complex system of neuron-OPC interactions and reveal a cell-autonomous role for glutamatergic signaling in OPCs during neural development.SIGNIFICANCE STATEMENT The migration of oligodendrocyte progenitor cells (OPCs) is an essential process during development that leads to uniform oligodendrocyte distribution and sufficient myelination for central nervous system function. Here, we demonstrate that the AMPA receptor (AMPAR) subunit GluR4A is an important driver of OPC migration and myelination in vivo and that activated voltage-gated calcium channels are downstream of glutamate receptor signaling in mediating this migration.

Routine Use of a Bougie Improves First-Attempt Intubation Success in the Out-of-Hospital Setting.

STUDY OBJECTIVE: The bougie is typically treated as a rescue device for difficult airways. We evaluate whether first-attempt success rate during paramedic intubation in the out-of-hospital setting changed with routine use of a bougie. METHODS: A prospective, observational, pre-post study design was used to compare first-attempt success rate during out-of-hospital intubation with direct laryngoscopy for patients intubated 18 months before and 18 months after a protocol change that directed the use of the bougie on the first intubation attempt. We included all patients with a paramedic-performed intubation attempt. Logistic regression was used to examine the association between routine bougie use and first-attempt success rate. RESULTS: Paramedics attempted intubation in 823 patients during the control period and 771 during the bougie period. The first-attempt success rate increased from 70% to 77% (difference 7.0% [95% confidence interval 3% to 11%]). Higher first-attempt success rate was observed during the bougie period across Cormack-Lehane grades, with rates of 91%, 60%, 27%, and 6% for Cormack-Lehane grade 1, 2, 3, and 4 views, respectively, during the control period and 96%, 85%, 50%, and 14%, respectively, during the bougie period. Intubation during the bougie period was independently associated with higher first-attempt success rate (adjusted odds ratio 2.82 [95% confidence interval 1.96 to 4.01]). CONCLUSION: Routine out-of-hospital use of the bougie during direct laryngoscopy was associated with increased first-attempt intubation success rate.

Elesclomol restores mitochondrial function in genetic models of copper deficiency.

Copper is an essential cofactor of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Inherited loss-of-function mutations in several genes encoding proteins required for copper delivery to CcO result in diminished CcO activity and severe pathologic conditions in affected infants. Copper supplementation restores CcO function in patient cells with mutations in two of these genes, COA6 and SCO2, suggesting a potential therapeutic approach. However, direct copper supplementation has not been therapeutically effective in human patients, underscoring the need to identify highly efficient copper transporting pharmacological agents. By using a candidate-based approach, we identified an investigational anticancer drug, elesclomol (ES), that rescues respiratory defects of COA6-deficient yeast cells by increasing mitochondrial copper content and restoring CcO activity. ES also rescues respiratory defects in other yeast mutants of copper metabolism, suggesting a broader applicability. Low nanomolar concentrations of ES reinstate copper-containing subunits of CcO in a zebrafish model of copper deficiency and in a series of copper-deficient mammalian cells, including those derived from a patient with SCO2 mutations. These findings reveal that ES can restore intracellular copper homeostasis by mimicking the function of missing transporters and chaperones of copper, and may have potential in treating human disorders of copper metabolism.

Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial.

Importance: For critically ill adults undergoing emergency tracheal intubation, failure to intubate the trachea on the first attempt occurs in up to 20% of cases and is associated with severe hypoxemia and cardiac arrest. Whether using a tracheal tube introducer ("bougie") increases the likelihood of successful intubation compared with using an endotracheal tube with stylet remains uncertain. Objective: To determine the effect of use of a bougie vs an endotracheal tube with stylet on successful intubation on the first attempt. Design, Setting, and Participants: The Bougie or Stylet in Patients Undergoing Intubation Emergently (BOUGIE) trial was a multicenter, randomized clinical trial among 1102 critically ill adults undergoing tracheal intubation in 7 emergency departments and 8 intensive care units in the US between April 29, 2019, and February 14, 2021; the date of final follow-up was March 14, 2021. Interventions: Patients were randomly assigned to use of a bougie (n = 556) or use of an endotracheal tube with stylet (n = 546). Main Outcomes and Measures: The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe hypoxemia, defined as a peripheral oxygen saturation less than 80%. Results: Among 1106 patients randomized, 1102 (99.6%) completed the trial and were included in the primary analysis (median age, 58 years; 41.0% women). Successful intubation on the first attempt occurred in 447 patients (80.4%) in the bougie group and 453 patients (83.0%) in the stylet group (absolute risk difference, -2.6 percentage points [95% CI, -7.3 to 2.2]; P = .27). A total of 58 patients (11.0%) in the bougie group experienced severe hypoxemia, compared with 46 patients (8.8%) in the stylet group (absolute risk difference, 2.2 percentage points [95% CI, -1.6 to 6.0]). Esophageal intubation occurred in 4 patients (0.7%) in the bougie group and 5 patients (0.9%) in the stylet group, pneumothorax was present after intubation in 14 patients (2.5%) in the bougie group and 15 patients (2.7%) in the stylet group, and injury to oral, glottic, or thoracic structures occurred in 0 patients in the bougie group and 3 patients (0.5%) in the stylet group. Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, use of a bougie did not significantly increase the incidence of successful intubation on the first attempt compared with use of an endotracheal tube with stylet. Trial Registration: ClinicalTrials.gov Identifier: NCT03928925

Cardiac Arrest in Flight: A Retrospective Chart Review of 92 Patients Transported by a Critical Care Air Medical Service.

OBJECTIVE: The purpose of this study was to describe the incidence, characteristics, and outcomes of cardiac arrest in the air medical environment so that we can begin to understand predictors of in-flight cardiac arrest and identify opportunities to improve care. METHODS: This retrospective observational study was undertaken at Airlift Northwest from 2013 to 2017. Descriptive statistics of adult patients with medical and traumatic etiologies of cardiac arrest were analyzed and compared. RESULTS: Of the 13,915 adult patients transported during the study period, fewer than 1% (N = 92) had a cardiac arrest during transport. Of those, 42% in the overall cohort had return of spontaneous circulation on arrival at the destination hospital. Medical etiologies of cardiac arrest were more common than traumatic (65% vs. 35%), more likely to have an initial shockable rhythm (30% vs. 3%, P = .004), and more frequently arrived at the receiving hospital with return of spontaneous circulation (57% vs. 31%, P = .03). Rearrest in transport occurred frequently (39%). Most patients were hypotensive before cardiac arrest, and peri-intubation cardiac arrest occurred in 12% of patients. CONCLUSION: Cardiac arrest during air medical transport is a rare event that requires a high level of critical care to treat refractory cardiac arrests, hemodynamic instability, and airway compromise.

Hemostatic Resuscitation of Pediatric Trauma Patients During Air Medical Transport: A Retrospective Matched Cohort Study.

OBJECTIVE: The objective of this study was to examine an academic air ambulance service's experience with prehospital transfusion of plasma and red blood cells in pediatric trauma for evidence of efficacy on the treatment of shock and coagulopathy. METHODS: All trauma patients < 18 years old transfused during transport by the University of Washington Airlift Northwest (Airlift) air medical transport service to Harborview Medical Center, Seattle, WA, were identified. Controls were matched 1:1 from pediatric trauma patients transported by Airlift before transfusion support became available. Demographics, injury scores, emergency department admission and interval laboratory values, blood product use, and hospital outcome measures were registered. RESULTS: Seventeen cases met the inclusion criteria and were matched by age and Injury Severity Score to 17 control patients (mean age = 10.5 vs. 10.9 years; New Injury Severity Score, 37 vs. 40.7). No significant differences in vital signs, shock index, or mortality were observed. Cases received less in-flight crystalloid (4.3 mL/kg vs. 16.9 mL/kg, P = .004), had higher admission fibrinogen levels (238 vs. 148mg/dL, P = .007), and shorter time to normalization of the international normalized ratio (6.4 vs. 19.1 hours, P = .04). CONCLUSIONS: In this small series, hemostatic resuscitation during air medical transport was associated with less crystalloid administration and better support of coagulation indices.

Suspected Succinylcholine-Induced Masseter Muscle Rigidity During Rapid Sequence Intubation in the Air Medical Setting.

Trismus, or masseter muscle rigidity, is a rare but previously described complication of succinylcholine-induced neuromuscular blockade. We present a case report that details unique aspects of suspected masseter muscle rigidity in the prehospital setting air medical setting after attempted rapid sequence intubation with succinylcholine. We then discuss the need for knowledge base of this life-threatening and rarely described syndrome as well as the importance of working through a differential diagnosis and specific trismus-focused airway algorithm. Trismus, or masseter muscle rigidity (MMR), is a rare but previously described complication of succinylcholine-induced neuromuscular blockade. It has been cited in anesthesia and emergency medicine literature as a potentially life-threatening complication and requires prompt intervention. This case report details a unique case of suspected MMR in the prehospital setting after attempted rapid sequence intubation (RSI) with succinylcholine performed by an experienced aeromedical flight crew.

Difficult Intubation due to Penetrating Trauma from a Crossbow Bolt.

We present the case of a patient with penetrating neck and craniofacial trauma from a self-inflicted crossbow bolt injury. This case highlights the challenges involved in prehospital airway management related to an in situ foreign object penetrating the oral cavity. We review the complications associated with such injuries and considerations for effective prehospital airway management.

Iatrogenic pediatric hydroxocobalamin overdose.

INTRODUCTION: Hydroxocobalamin, a precursor molecule to vitamin B12, has emerged as the preferred empiric treatment for patients rescued from enclosed-space fires with concern for inhalational injury and potential concomitant cyanide toxicity. Limited data exist on the effects of hydroxocobalamin toxicity, particularly in pediatric patients. CASE REPORT: We report a case of a healthy three-year old girl who was rescued from an apartment fire and electively intubated by prehospital providers. Due to concern for potential cyanide toxicity, she received 5 g (373 mg/kg) of intravenous hydroxocobalamin, an amount equivalent to one standard adult dose but over five times the appropriate weight-adjusted dose for this 13.4-kilogram child. On hospital arrival, patient was noted to have chromaturia and diffuse erythroderma without cutaneous burns. She was extubated 4 h after prehospital intubation and discharged home the following morning in good condition with persistent erythroderma. Skin color returned to normal within two days. DISCUSSION: We believe this to be the first reported case of iatrogenic pediatric hydroxocobalamin overdose for the treatment of suspected cyanide toxicity. Erythroderma and chromaturia are expected side effects of hydroxocobalamin, even at therapeutic levels. Along with minor airway burns, the only other finding was a transient and hemodynamically neutral bradycardia, which began shortly after prehospital intubation. As this bradycardia occurred prior to hydroxocobalamin administration, more likely culprits include vagal nerve stimulation from direct laryngoscopy, and sinoatrial muscarinic receptor stimulation caused by repeated doses of succinylcholine. In all, we were unable to appreciate any complications due to excess hydroxocobalamin administration.

Syringe Administration of Epinephrine by Emergency Medical Technicians for Anaphylaxis.

OBJECTIVE: In recent years, the costs of epinephrine autoinjectors (EAIs) in the United States have risen substantially. King County Emergency Medical Services implemented the "Check and Inject" program to replace EAIs by teaching emergency medical technicians (EMTs) to manually aspirate epinephrine from a single-use 1 mg/mL epinephrine vial using a needle and syringe followed by prehospital intramuscular administration of the correct adult or pediatric dose of epinephrine for anaphylaxis or serious allergic reaction. Treatment was guided by an EMT protocol that required a trigger and symptoms. We sought to determine if the "Check and Inject" program was safely implemented by EMTs treating presumed prehospital anaphylaxis or serious allergic reaction. METHODS: We conducted a prospective investigation of all cases treated as part of the "Check and Inject" program from July 2014 through December 2016 in suburban King County, Washington, and January 2016 through December 2016 within the city of Seattle. All cases were prospectively collected using a custom quality improvement data form completed by the first responding EMTs. Two physicians completed a structured review of each EMS medical record to determine if the EMTs followed the Check and Inject protocol and determine if epinephrine was clinically-indicated based on physician review. RESULTS: Of the 411 cases eligible for analysis, EMTs followed the protocol appropriately in 367 (89.3%) cases. In the remaining 44 (10.7%) cases, the EMS incident report form failed to document either a clear inciting allergic trigger or an appropriate symptom from the protocol list. Physician review determined that epinephrine was clinically indicated in 36 of the 44 cases. Among the remaining 8 cases (1.9%) that did not meet protocol criteria and were not clinically-indicated based on physician review, none had a documented adverse reaction to the epinephrine. CONCLUSION: We observed that EMTs successfully implemented the manual "Check and Inject" program for severe allergic reactions and anaphylaxis in a manner that typically agreed with physician review and without any overt identified safety issues.

Resuscitative Airway Management for Massive Gastrointestinal Hemorrhage.

Massive upper gastrointestinal hemorrhage represents a highly morbid, resource intensive disease entity that requires rapid diagnostic and therapeutic delivery in parallel with mobilization of in-hospital providers for definitive intervention. This report details a unique case demonstrating exceptional collaboration spanning multiple healthcare systems, a novel use of resuscitative endovascular balloon occlusion of the aorta, and a discussion on resuscitative airway management in the setting of massive upper gastrointestinal hemorrhage.

THE COMPENSATORY RESERVE INDEX FOR PREDICTING HEMORRHAGIC SHOCK IN PREHOSPITAL TRAUMA.

ABSTRACT: Background: The compensatory reserve index (CRI) is a noninvasive, continuous measure designed to detect intravascular volume loss. CRI is derived from the pulse oximetry waveform and reflects the proportion of physiologic reserve remaining before clinical hemodynamic decompensation. Methods: In this prospective, observational, prehospital cohort study, we measured CRI in injured patients transported by emergency medical services (EMS) to a single Level I trauma center. We determined whether the rolling average of CRI values over 60 s (CRI trend [CRI-T]) predicts in-hospital diagnosis of hemorrhagic shock, defined as blood product administration in the prehospital setting or within 4 h of hospital arrival. We hypothesized that lower CRI-T values would be associated with an increased likelihood of hemorrhagic shock and better predict hemorrhagic shock than prehospital vital signs. Results: Prehospital CRI was collected on 696 adult trauma patients, 21% of whom met our definition of hemorrhagic shock. The minimum CRI-T was 0.14 (interquartile range [IQR], 0.08-0.31) in those with hemorrhagic shock and 0.31 (IQR 0.15-0.50) in those without ( P = <0.0001). The positive likelihood ratio of a CRI-T value <0.2 predicting hemorrhagic shock was 1.85 (95% confidence interval [CI], 1.55-2.22). The area under the ROC curve (AUC) for the minimum CRI-T predicting hemorrhagic shock was 0.65 (95% CI, 0.60-0.70), which outperformed initial prehospital HR (0.56; 95% CI, 0.50-0.62) but underperformed EMS systolic blood pressure and shock index (0.74; 95% CI, 0.70-0.79 and 0.72; 95% CI, 0.67-0.77, respectively). Conclusions: Low prehospital CRI-T predicts blood product transfusion by EMS or within 4 hours of hospital arrival but is less prognostic than EMS blood pressure or shock index. The evaluated version of CRI may be useful in an austere setting at identifying injured patients that require the most significant medical resources. CRI may be improved with noise filtering to attenuate the effects of vibration and patient movement.

Association of small adult ventilation bags with return of spontaneous circulation in out of hospital cardiac arrest.

INTRODUCTION: Little is known about the impact of tidal volumes delivered by emergency medical services (EMS) to adult patients with out-of-hospital cardiac arrest (OHCA). A large urban EMS system changed from standard adult ventilation bags to small adult bags. We hypothesized that the incidence of return of spontaneous circulation (ROSC) at the end of EMS care would increase after this change. METHODS: We performed a retrospective analysis evaluating adults treated with advanced airway placement for nontraumatic OHCA between January 1, 2015 and December 31, 2021. We compared rates of ROSC, ventilation rate, and mean end tidal carbon dioxide (ETCO2) by minute before and after the smaller ventilation bag implementation using linear and logistic regression. RESULTS: Of the 1,994 patients included, 1,331 (67%) were treated with a small adult bag. ROSC at the end of EMS care was lower in the small bag cohort than the large bag cohort, 33% vs 40% (p = 0.003). After adjustment, small bag use was associated with lower odds of ROSC at the end of EMS care [OR 0.74, 95% CI 0.61 - 0.91]. Ventilation rates did not differ between cohorts. ETCO2 values were lower in the large bag cohort (33.2 ± 17.2 mmHg vs. 36.9 ± 19.2 mmHg, p < 0.01). CONCLUSION: Use of a small adult bag during OHCA was associated with lower odds of ROSC at the end of EMS care. The effects on acid base status, hemodynamics, and delivered minute ventilation remain unclear and warrant additional study.