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We sought to determine if the difference between PThis was a retrospective cohort study of adult patients who achieved return of spontaneous circulation (ROSC) after OHCA over 3 years. The primary exposure was the POf 698 OHCA patients transported to the hospitals, 381 had sustained ROSC and qualifying ENeither P

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.

Guidelines recommend monitoring end-tidal carbon dioxide (EThis retrospective, observational cohort analysis included adult OHCA patients who received a defibrillation shock during treatment by an urban EMS agency from 2015 to 2021. Peak EOf 518 eligible patients, mean age was 61, 72% were male, 50% had a bystander-witnessed arrest, and 62% had at least one episode of ROSC. The most common arrest etiology was medical (92%). Among all patients, peak EE

We investigated the risk of coronavirus disease (COVID-19)­ patients transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to emergency medical service (EMS) providers, stratified by aerosol-generating procedures (AGP), in King County, Washington, USA, during February 16–July 31, 2020. We conducted a retrospective cohort investigation using a statewide COVID-19 registry and identified 1,115 encounters, 182 with ≥1 AGP. Overall, COVID-19 incidence among EMS personnel was 0.57 infections/10,000 person-days. Incidence per 10,000 person-days did not differ whether or not infection was attributed to a COVID-19 patient encounter (0.28 vs. 0.59; p>0.05). The 1 case attributed to a COVID-19 patient encounter occurred within an at-risk period and involved an AGP. We observed a very low risk for COVID-19 infection attributable to patient encounters among EMS first responders, supporting clinical strategies that maintain established practices for treating patients in emergency conditions.

Chest compressions during CPR induce oscillations in capnography (EWe conducted a retrospective study of 307 out-of-hospital cardiac arrest (OHCA) cases in Seattle, WA during 2019. EMedian [interquartile range] AOI across all cases using Methods 1-4 was 28.0 % [17.9-45.5 %], 20.6 % [13.0-36.6 %], 18.3 % [11.4-30.4 %], and 22.4 % [12.8-38.5 %], respectively (p 0.001). Cases with ROSC had a higher median AOI than those without ROSC across all methods, though not statistically significant. Cases with ROSC had a significantly higher median [interquartile range] ΔEWe calculated AOI using four proposed methods resulting in significantly different AOI. Additionally, AOI and ΔE

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

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.

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.All trauma patients18 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.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).In this small series, hemostatic resuscitation during air medical transport was associated with less crystalloid administration and better support of coagulation indices.

BACKGROUND International guidelines emphasize advanced airway management during out-of-hospital cardiac arrest (OHCA). We hypothesized that increasing endotracheal intubation attempts during OHCA were associated with a lower likelihood of favorable neurologic survival at discharge. METHODS This retrospective, observational cohort evaluated the relationship between number of intubation attempts and favorable neurologic survival among non-traumatic OHCA patients receiving cardiopulmonary resuscitation (CPR) from January 1, 2015-June 30, 2019 in a large urban emergency medical services (EMS) system. Favorable neurologic status at hospital discharge was defined as a Cerebral Performance Category score of 1 or 2. Multivariable logistic regression, adjusted for age, sex, witness status, bystander CPR, initial rhythm, and time of EMS arrival, was performed using the number of attempts as a continuous variable. RESULTS Over 54 months, 1205 patients were included. Intubation attempts per case were 1 = 757(63%), 2 = 279(23%), 3 = 116(10%), ≥4 = 49(4%), and missing/unknown in 4(

BACKGROUND Rapid air transport of critically injured patients to sites of appropriate care can save lives. The provision of blood products on critical care transport flights may save additional lives by starting resuscitation earlier. METHODS Our regional trauma center transfusion service provided 2 units of O-negative red blood cells and 2 units of A low-titer anti-B liquid plasma in an internally monitored and sealed eutectic box weighing 10.4 pounds to eight air bases once weekly. Flight crews were instructed to transfuse plasma units first. Unused blood was returned to the transfusion service. Total blood use and wastage were recorded. RESULTS Over a 6-year period, ≈ 7400 blood components were provided, and >1000 were used by the air transport service in patient care. Plasma units were 57% of all units given. Unused units were returned to the providing transfusion service and used in hospital patient care with

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.

Background Interruptions in chest compressions contribute to poor outcomes in out‐of‐hospital cardiac arrest. The objective of this retrospective observational cohort study was to characterize the frequency, reasons, and duration of interruptions in chest compressions and to determine if interruptions changed over time. Methods and Results All out‐of‐hospital cardiac arrests treated by the Seattle Fire Department (Seattle, WA, United States) from 2007 to 2016 with capture of recordings from automated external defibrillators and manual defibrillators were included. Compression interruptions >1 second were classified into categories using audio recordings. Among the 3601 eligible out‐of‐hospital cardiac arrests, we analyzed 74 584 minutes, identifying 30 043 pauses that accounted for 6621 minutes (8.9% of total resuscitation duration). The median total interruption duration per case decreased from 115 seconds in 2007 to 72 seconds in 2016 ( P P 10 seconds, median interruption duration decreased from 20 seconds in 2007 to 16 seconds in 2016 ( P ECG rhythm analysis and pulse checks accounted for 41.6% of all interruption time (median individual interruption, 8 seconds), automated external defibrillator rhythm analysis for 13.7% (median, 17 seconds), and manual rhythm analysis and shock delivery for 8.0% (median, 9 seconds). Conclusions Median duration of chest compression interruptions decreased by half from 2007 to 2016, indicating that care teams can significantly improve performance. Reducing compression interruptions is an evidence‐based benchmark that provides a modifiable process quality improvement goal.

Significance Inherited pathogenic mutations in genes required for copper delivery to cytochrome c oxidase (CcO) perturb mitochondrial energy metabolism and result in fatal mitochondrial disease. A prior attempt to treat human patients with these mutations by direct copper supplementation was not successful, possibly because of inefficient copper delivery to the mitochondria. We performed a targeted search to identify compounds that can efficiently transport copper across biological membranes and identified elesclomol (ES), an investigational anticancer drug, as the most efficient copper delivery agent. ES rescues CcO function in yeast, zebrafish, and mammalian models of copper deficiency by increasing cellular and mitochondrial copper content. Thus, our study offers a possibility of repurposing this anticancer drug for the treatment of disorders of copper metabolism., 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.

Aeromedical prehospital care has seen an increase in the use of point-of-care-ultrasound (POCUS) in recent years. Prior research has focused on abdominal trauma exams by physician or advanced practice providers. In this study, we describe the implementation of an ultrasound curriculum designed for Flight Nurse assessment of pneumothorax and esophageal intubation. The study team conducted three one-hour training sessions over two months. The training curriculum included didactic and hands-on components. We enrolled twelve flight nurses with no prior ultrasound experience. A pre- and post-test was administered consisting of fifteen questions. The median pre-test score was seven correct for an average of 45.0%. After the training session, the median post-test score was fourteen correct for an average of 90.6%. The training intervention resulted in an average improvement in score of 45.6%. While not examining skill acquisition, we are encouraged by the implementation of this curriculum for future ultrasound education in esophageal intubation and pneumothorax.

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.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.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.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.

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.

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.

Summary 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-1β. Taken together, our results reveal a role for NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes.

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.

During neural tube closure and subsequent spinal cord development, a vast number of cells undergo programmed cell death 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 early development remains largely unknown. Using live imaging in zebrafish, we demonstrate that multipotent neural crest cells (NCC) respond rapidly to dying cells and phagocytose cellular debris around the neural tube. Furthermore, migratory NCCs have the ability to enter the CNS through motor exit point transition zones and clear debris in the spinal cord. Surprisingly, NCC phagocytosis mechanistically resembles macrophage phagocytosis and their recruitment towards cellular debris is mediated by interleukin-1β signaling. Taken together, our results reveal an unexpected role of NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes.

The care for victims of out-of-hospital cardiac arrest is evolving and will be influenced by future and emerging technologies that will play a role in the systems of care for these patients. Recent advances in extracorporeal life support and point-of-care ultrasound imaging, both in-hospital and out-of-hospital, may offer a therapeutic solution in some systems for patients with refractory or recurrent cardiac arrest. Drones capable of delivering automated external defibrillators to the scene of an out-of-hospital cardiac arrest, advances in digital and mobile technologies to notify and leverage bystander response, and wearable life detection technologies may improve survival.

Objectives Air emergency medical services (AEMS) are regularly employed in many parts of the world to transport severely ill or injured patients rapidly to definitive care. Out-of-hospital cardiac arrest (OHCA) is a potentially catastrophic event that may occur among a subset of the most severely ill patients that are encountered. This study describes the pre-arrest characteristics, treatments applied, and short-term outcomes of patients with OHCA treated by AEMS. Methods All adult patients who experienced OHCA at a single, academic aeromedical transport service between 2013–2017 were included in this retrospective analysis. All cases during which an adult patient suffered cardiac arrest occurring from the time of AEMS arrival at the scene or sending facility to hand off at the receiving facility were included. Data including standard Utstein variables, treatments, and short-term outcome were extracted by the authors. Univariate descriptive statistics were computed using SPSS ver. 25. Results During the 5-year period, 92 cases of adult OHCA were identified among 16,779 transports. The median age of patients experiencing OHCA was 64.5 years [55.3, 63.3]. Among patients transported, the average transport time was 75.4 minutes [63.4, 87.3]. 60 OHCA cases (65.2%) were of medical etiology and 32 (34.8%) were traumatic. Scene calls were the origin for 51.1% of calls; the rest were interfacility transfers. 36/92 patients (39.1%) had multiple cardiac arrests under AEMS care, and OHCA occurred for the first time most often before take-off: 39.1% at the initial scene, 29.3% in transit or loading to aircraft, and in flight 31.5% of the time. 17.4% of the cohort had an initial shockable rhythm and 42.4% achieved return of spontaneous circulation (ROSC) by arrival at the destination facility; an additional 5.4% achieved ROSC and were not transported. Conclusions In this cohort, OHCA occurred in 92 adult patients over 5 years, with approximately two thirds medical and one third traumatic in nature. Initial rhythm was rarely shockable, but sustained ROSC was achieved in almost half the patients. Almost 4 in 10 patients had multiple cardiac arrests under AEMS care, and initial arrest was most likely to occur prior to air transport as opposed to in flight. A high proportion of patients achieving ROSC is possible, even with relatively low rates of shockable initial rhythm. This study suggests that while cardiac arrest in flight is rare, medical teams must be prepared to handle both medical and traumatic arrests as well as multiple arrests during the course of air transport.

International guidelines recommend administration of 1 mg of intravenous epinephrine every 3-5 min during cardiac arrest. The optimal dose of epinephrine is not known. We evaluated the association of reduced frequency and dose of epinephrine with survival after out-of-hospital cardiac arrest (OHCA).Included were patients with non-traumatic OHCA treated by advanced life support (ALS) providers from January 1, 2008 to June 30, 2016. During the before period, providers were instructed to give epinephrine 1 mg intravenously at 4 min followed by additional 1 mg doses every eight minutes to patients with OHCA with a shockable rhythm and 1 mg doses every two minutes to patients with a non-shockable rhythm (higher dose). On October 1, 2012, providers were instructed to reduce the dose of epinephrine treatment during out-of-hospital cardiac arrest (OHCA): 0.5 mg at 4 and 8 min followed by additional doses of 0.5 mg every 8 min for shockable rhythms and 0.5 mg every 2 min for non-shockable rhythms (lower dose). Patients with shockable initial rhythms were analyzed separately from those with non-shockable initial rhythms. The primary outcome was survival to hospital discharge with a secondary outcome of favorable neurological status (Cerebral Performance Category [CPC] 1 or 2) at hospital discharge. Multiple logistic regression modeling was used to adjust for age, sex, presence of a witness, bystander CPR, and response interval.2255 patients with OHCA were eligible for analysis. Of these, 24.6% had an initially shockable rhythm. Total epinephrine dose per patient decreased from a mean ± standard deviation of 3.4 ± 2.3 mg-2.6 ± 1.9 mg (p 0.001) in the shockable group and 3.5 ± 1.9 mg-2.8 ± 1.7 mg (p 0.001) in the non-shockable group. Among those with a shockable rhythm, survival to hospital discharge was 35.0% in the higher dose group vs. 34.2% in the lower dose group. Among those with a non-shockable rhythm, survival was 4.2% in the higher dose group vs. 5.1% in the lower dose group. Lower dose vs. higher dose was not significantly associated with survival: adjusted odds ratio, aOR 0.91 (95% CI 0.62-1.32, p = 0.61) if shockable and aOR 1.26 (95% CI 0.79-2.01, p = 0.33) if non-shockable. Lower dose vs. higher dose was not significantly associated with favorable neurological status at discharge: aOR 0.84 (95% CI 0.57-1.24, p = 0.377) if shockable and aOR 1.17 (95% CI 0.68-2.02, p = 0.577) if non-shockable.Reducing the dose of epinephrine administered during out-of-hospital cardiac arrest was not associated with a change in survival to hospital discharge or favorable neurological outcomes after OHCA.

Myelinating oligodendrocytes arise from migratory and proliferative oligodendrocyte progenitor cells (OPCs). Complete myelination requires that oligodendrocytes be uniformly distributed and form numerous, periodically spaced membrane sheaths along the entire length of target axons. Mechanisms that determine spacing of oligodendrocytes and their myelinating processes are not known. Using in vivo time-lapse confocal microscopy, we show that zebrafish OPCs continuously extend and retract numerous filopodium-like processes as they migrate and settle into their final positions. Process remodeling and migration paths are highly variable and seem to be influenced by contact with neighboring OPCs. After laser ablation of oligodendrocyte-lineage cells, nearby OPCs divide more frequently, orient processes toward the ablated cells and migrate to fill the unoccupied space. Thus, process activity before axon wrapping might serve as a surveillance mechanism by which OPCs determine the presence or absence of nearby oligodendrocyte-lineage cells, facilitating uniform spacing of oligodendrocytes and complete myelination.

Notochord and floor plate cells are sources of molecules that pattern tissues near the midline, including the spinal cord. Hypochord cells are also found at the midline of anamniote embryos and are important for aorta development. Delta–Notch signaling regulates midline patterning in the dorsal organizer by inhibiting notochord formation and promoting hypochord and possibly floor plate development, but the precise mechanisms by which this regulation occurs are unknown. We demonstrate here that floor plate and hypochord cells arise from distinct regions of the zebrafish shield. Blocking Notch signaling during gastrulation entirely prevented hypochord specification but only reduced the number of floor plate cells that developed compared to control embryos. In contrast, elevation of Notch signaling at the beginning of gastrulation caused expansion of hypochord at the expense of notochord, but floor plate was not affected. A cell proliferation assay revealed that Notch signaling maintains dividing floor plate progenitors. Together, our results indicate that Notch signaling regulates allocation of appropriate numbers of different midline cells by different mechanisms.

SummaryVertebrate body plans have a conserved left-right (LR) asymmetry manifested in the position and anatomy of the heart, visceral organs, and brain. Recent studies have suggested that LR asymmetry is established by asymmetric Ca2+ signaling resulting from cilia-driven flow of extracellular fluid across the node. We report here that inositol 1,3,4,5,6-pentakisphosphate 2-kinase (Ipk1), which generates inositol hexakisphosphate, is critical for normal LR axis determination in zebrafish. Zebrafish embryos express ipk1 symmetrically during gastrulation and early segmentation. ipk1 knockdown by antisense morpholino oligonucleotide injection randomized LR-specific gene expression and organ placement, effects that were associated with reduced intracellular Ca2+ flux in cells surrounding the ciliated Kupffer’s vesicle, a structure analogous to the mouse node. Our data suggest that the pathway for inositol hexakisphosphate production is a key regulator of asymmetric Ca2+ flux during LR specification.

Different cell types that occupy the midline of vertebrate embryos originate within the Spemann-Mangold or gastrula organizer. One such cell type is hypochord, which lies ventral to notochord in anamniote embryos. We show that hypochord precursors arise from the lateral edges of the organizer in zebrafish. During gastrulation, hypochord precursors are closely associated with no tail-expressing midline precursors and paraxial mesoderm, which expresses deltaC and deltaD. Loss-of-function experiments revealed that deltaC and deltaD were required for her4 expression in presumptive hypochord precursors and for hypochord development. Conversely, ectopic, unregulated Notch activity blocked no tail expression and promoted her4 expression. We propose that Delta signaling from paraxial mesoderm diversifies midline cell fate by inducing a subset of neighboring midline precursors to develop as hypochord, rather than as notochord.

We investigated the effects of endothelins (ETs) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ET-3 increased cGMP formation in a concentration-dependent manner (EC50 = 98nM), which was 2.5 times higher than that of ET-1. The ET(B)receptor agonists sarafotoxin-S6c and IRL 1620 also increased cGMP production, mimicking the effects of the ETs. The ET(B) receptor antagonist BQ 788, but not the ET(A) receptor antagonist BQ610, dose-dependently blocked ET-3-stimulated cGMP formation (IC50=10nM). The phorbol ester, Phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylyl cyclase in smooth muscle, dose-dependently inhibited ET-3-stimulated cGMP accumulation (IC50=66nM). LY83583 and ODQ, inhibitors of soluble guanylyl cyclases, as well as inhibitors of the nitric oxide cascade and of intracellular Ca2+ elevation had no appreciable effect on ET-3-induced cGMP production. ET-3 markedly inhibited carbachol-induced intracellular Ca2+ mobilization. We conclude that ET-3 increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ET(B) receptor subtype and subsequent stimulation of the membrane-bound guanylyl cyclase. Elevation of cGMP by ET and the subsequent inhibition of muscarinic stimulation of intracellular Ca2+ mobilization by the cyclic nucleotide could serve to modulate the contractile effects of Ca2+-mobilizing agonists in the iris sphincter smooth muscle.

Objective To investigate the identification of maternal deaths at the community level using the reproductive age mortality survey (RAMOS) in all households in which a women of reproductive age (WRA) died and to determine the most concise subset of questions for identifying a pregnancy-related death for further investigation. Methods A full RAMOS survey was conducted with the families of 46 deceased WRA who died between 2005 and July 2009 and was compared with the cause of death confirmed by the maternal mortality review committee to establish the number of maternal mortalities. The positive predictive value (PPV) of each RAMOS question for identifying a maternal death was determined. Results Compared with years of voluntary reporting, active surveillance for maternal deaths doubled their identification. In addition, 4 questions from the full RAMOS have the highest PPV for a maternal death including the question: "Was she pregnant within the last 6 weeks?" which had a 100% PPV and a 100% negative predictive value. Conclusion Active identification of maternal mortality at the community level by using a 4-question modified RAMOS that is systematically administered in the local language by health workers can increase understanding of the extent of maternal mortality in rural Ghana.

Notochord, floor plate, and in anamniotes hypochord, are vertebrate embryonic midline structures that are the sources of molecules that pattern the nervous system, somites, and dorsal aorta. Midline precursor cells arise from the dorsal organizer during gastrulation, and Notch signaling is an important regulator of midline cell fate specification. To understand fully how Notch signaling regulates midline development, we investigated the role of potential Notch target genes. We show here that midline precursors express her9, a member of the hairy/Enhancer of split gene family. Although her9 inhibits notochord development and promotes floor plate specification, her9 expression in floor plate cells appears not to require Notch signaling. We show that, instead, her9 is a downstream effector of Nodal signaling for floor plate specification.