The association of recent simulation training and clinical experience of team leaders with cardiopulmonary resuscitation quality during in-hospital cardiac arrest.

OBJECTIVE: We aimed to investigate the association of recent team leader simulation training (<6 months) and years of clinical experience (≥4 years) with chest compression quality during in-hospital cardiac arrest (IHCA). METHODS: This cohort study of IHCA in four Danish hospitals included cases with data on chest compression quality and team leader characteristics. We assessed the impact of recent simulation training and experienced team leaders on longest chest compression pause duration (primary outcome), chest compression fraction (CCF), and chest compression rates within guideline recommendations using mixed effects models. RESULTS: Of 157 included resuscitation attempts, 45% had a team leader who recently participated in simulation training and 66% had an experienced team leader. The median team leader experience was 7 years [Q1; Q3: 4; 11]. The median duration of the longest chest compression pause was 16 s [10; 30]. Having a team leader with recent simulation training was associated with significantly shorter longest pause durations (difference: -7.11 s (95%-CI: -12.0; -2.2), p = 0.004), a higher CCF (difference: 3% (95%-CI: 2.0; 4.0%), p < 0.001) and with less guideline compliant chest compression rates (odds ratio: 0.4 (95%-CI: 0.19; 0.84), p = 0.02). Having an experienced team leader was not associated with longest pause duration (difference: -1.57 s (95%-CI: -5.34; 2.21), p = 0.42), CCF (difference: 0.7% (95%-CI: -0.3; 1.7), p = 0.17) or chest compression rates within guideline recommendations (odds ratio: 1.55 (95%-CI: 0.91; 2.66), p = 0.11). CONCLUSION: Recent simulation training of team leaders, but not years of team leader experience, was associated with shorter chest compression pauses during IHCA.

[Layperson basic life support education in Austria: An overview]. / Laienreanimationstraining in Österreich: Eine Übersicht und Annäherung.

Early interventions of laypersons can improve the survival and neurological outcome in patients with out-of-hospital cardiac arrest. There are several organizations in Austria which train lay people in basic life support and raise awareness for sudden cardiac death. To obtain an overview of the various initiatives, a questionnaire was sent to 26 organizations, and 15 of the organizations (58%) replied. The geographical distribution of the organizations between rural and urban areas was illustrated in a map. Most of them are situated in a university city, resulting in accessibility disparities for individuals in urban and rural settings. Layperson resuscitation education in Austria is largely dependent on the individual commitments of volunteers. The time spent practicing chest compressions in resuscitation courses ranges from 25% to 90% of the total course time. Furthermore, reasons for a lack of scientific endeavours could be identified, and solutions are suggested. Through better networking between organizations and initiatives, more laypersons could be trained in the future, which would lead to improved survival chances for persons suffering from out-of-hospital cardiac arrest in Austria. Appropriate support by political bodies and public authorities is and will remain a key element.

The Young European Resuscitation Council Resuscitation Science Masterclass - Concept and implementation.

Nurturing the development of the next generation of resuscitation scientists is essential for creating a vibrant and enabled community equipped with the necessary knowledge, attitudes, and skills to transform resuscitation practice and improve outcomes. In this concept paper we will describe the development and implementation of the first Young European Resuscitation Council Resuscitation Science Masterclass. The masterclass aims to connect, inspire, and support the growth of the next generation of resuscitation scientists through education, networking, and joint scientific work. The masterclass provides 20 international, multi-professional early career resuscitation scientists with the opportunity to expand their knowledge and network as well as conduct joint scientific work over the course of one year. This is achieved by interactive webinars, innovative online workshops, engaging online journal clubs as well as an educational in-person event to conclude the masterclass. The Young European Resuscitation Council Resuscitation Science Masterclass aims to strengthen the global resuscitation community and next generation of resuscitation scientists by facilitating opportunities of broader international initiatives and collaboration for early career resuscitation scientists, potentially leading to accelerated recruitment of future resuscitation leaders. Ultimately, this masterclass may enable early career researchers to produce high impact research that can shape the future of resuscitation science and improve cardiac arrest patient care globally.

Assessing the weak links - Necessity and impact of regional cardiac arrest awareness campaigns for laypersons.

Introduction: Public knowledge of out-of-hospital cardiac arrest (OHCA), and initiation of basic life support (BLS) is crucial to increase survival in OHCA. Methods: The study analysed the knowledge and willingness to perform BLS of laypersons passing an AED at a public train station. Interviewees were recruited at two time points before and after a four year-long structured regional awareness campaign, which focused on call, compress, shock in a mid-size European city (270,000 inhabitants). Complete BLS was defined as multiple responses for call for help; initiation of chest compressions; and usage of an AED, without mentioning recovery position. Minimal BLS was defined as call for help and initiation of chest compressions. Results: A total of 784 persons were interviewed, 257 at baseline and 527 post-campaign. Confronted with a fictional OHCA, at baseline 8.5% of the interviewees spontaneously mentioned actions for complete BLS and 17.9% post-campaign (p = 0.009). An even larger increase in knowledge was seen in minimal BLS (34.6% vs 60.6%, p < 0.001). Conclusion: After a regional cardiac arrest awareness campaign, we found an increase in knowledge of BLS actions in the lay public. However, our investigation revealed severe gaps in BLS knowledge, possibly resulting in weak first links of the chain of survival.

Data for: Reliability of mechanical ventilation during continuous chest compressions: A crossover study of transport ventilators in a human cadaver model of CPR.

The data presented in this article relate to the research article, "Reliability of mechanical ventilation during continuous chest compressions: a crossover study of transport ventilators in a human cadaver model of CPR" [1]. This article contains raw data of continuous recordings of airflow, airway and esophageal pressure during the whole experiment. Data of mechanical ventilation was obtained under ongoing chest compressions and from repetitive measurements of pressure-volume curves. All signals are presented as raw time series data with a sample rate of 200Hz for flow and 500 Hz for pressure. Additionally, we hereby publish extracted time series recordings of force and compression depth from the used automated chest compression device. Concomitantly, we report tables with time stamps from our laboratory book by which the data can be sequenced into different phases of the study protocol. We also present a dataset of derived volumes which was used for statistical analysis in our research article together with the used exclusion list. The reported dataset can help to understand mechanical properties of Thiel-embalmed cadavers better and compare different models of cardiopulmonary resuscitation (CPR). Future research may use this data to translate our findings from bench to bedside. Our recordings may become useful in developing respiratory monitors for CPR, especially in prototyping and testing algorithms of such devices.

Reliability of mechanical ventilation during continuous chest compressions: a crossover study of transport ventilators in a human cadaver model of CPR.

BACKGROUND: Previous studies have stated that hyperventilation often occurs in cardiopulmonary resuscitation (CPR) mainly due to excessive ventilation frequencies, especially when a manual valve bag is used. Transport ventilators may provide mandatory ventilation with predetermined tidal volumes and without the risk of hyperventilation. Nonetheless, interactions between chest compressions and ventilations are likely to occur. We investigated whether transport ventilators can provide adequate alveolar ventilation during continuous chest compression in adult CPR. METHODS: A three-period crossover study with three common transport ventilators in a cadaver model of CPR was carried out. The three ventilators 'MEDUMAT Standard²', 'Oxylog 3000 plus', and 'Monnal T60' represent three different interventions, providing volume-controlled continuous mandatory ventilation (VC-CMV) via an endotracheal tube with a tidal volume of 6 mL/kg predicted body weight. Proximal airflow was measured, and the net tidal volume was derived for each respiratory cycle. The deviation from the predetermined tidal volume was calculated and analysed. Several mixed linear models were calculated with the cadaver as a random factor and ventilator, height, sex, crossover period and incremental number of each ventilation within the period as covariates to evaluate differences between ventilators. RESULTS: Overall median deviation of net tidal volume from predetermined tidal volume was - 21.2 % (IQR: 19.6, range: [- 87.9 %; 25.8 %]) corresponding to a tidal volume of 4.75 mL/kg predicted body weight (IQR: 1.2, range: [0.7; 7.6]). In a mixed linear model, the ventilator model, the crossover period, and the cadaver's height were significant factors for decreased tidal volume. The estimated effects of tidal volume deviation for each ventilator were - 14.5 % [95 %-CI: -22.5; -6.5] (p = 0.0004) for 'Monnal T60', - 30.6 % [95 %-CI: -38.6; -22.6] (p < 0.0001) for 'Oxylog 3000 plus' and - 31.0 % [95 %-CI: -38.9; -23.0] (p < 0.0001) for 'MEDUMAT Standard²'. CONCLUSIONS: All investigated transport ventilators were able to provide alveolar ventilation even though chest compressions considerably decreased tidal volumes. Our results support the concept of using ventilators to avoid excessive ventilatory rates in CPR. This experimental study suggests that healthcare professionals should carefully monitor actual tidal volumes to recognise the occurrence of hypoventilation during continuous chest compressions.

The Chicken as a Model Organism to Study Heart Development.

Heart development is a complex process and begins with the long-range migration of cardiac progenitor cells during gastrulation. This culminates in the formation of a simple contractile tube with multiple layers, which undergoes remodeling into a four-chambered heart. During this morphogenesis, additional cell populations become incorporated. It is important to unravel the underlying genetic and cellular mechanisms to be able to identify the embryonic origin of diseases, including congenital malformations, which impair cardiac function and may affect life expectancy or quality. Owing to the evolutionary conservation of development, observations made in nonamniote and amniote vertebrate species allow us to extrapolate to human. This review will focus on the contributions made to a better understanding of heart development through studying avian embryos-mainly the chicken but also quail embryos. We will illustrate the classic and recent approaches used in the avian system, give an overview of the important discoveries made, and summarize the early stages of cardiac development up to the establishment of the four-chambered heart.

Cardiac injections of AntagomiRs as a novel tool for knockdown of miRNAs during heart development.

BACKGROUND: Studying microRNA networks during heart development is essential to obtain a better understanding of developmental defects and diseases associated with the heart and to identify novel opportunities for therapeutics. Here we highlight the advantages of chicken embryos as a vertebrate model for studying intermediate processes of heart development. Avians develop a four-chambered heart closely resembling human anatomy and they develop ex utero, which makes them easily accessible. Furthermore, embryos are available all year with a steady supply. RESULTS: In this report we established a novel method for the knockdown of microRNA function by microinjecting AntagomiRs into the chicken heart in ovo. Our approach enables the targeted delivery of antagomirs into a locally restricted area and is not impacted by circulation. After further embryo development the successful miRNA knockdown was confirmed. Loss of function phenotypes can be evaluated rapidly, compared to more time-consuming genetic ablation experiments. The local application avoids potential systemic effects of microRNA knockdown, therefore allowing the assessment of impacts on heart development only. The method can be adjusted for different stages of chicken embryos (HH13-HH18) as well as for knockdown or targeted overexpression of coding genes. CONCLUSION: In conclusion our method allows targeted and locally restricted delivery of Antagomirs to the heart leading to successful knockdown of microRNA function. This method enables rapid phenotypic assessment, for example by gene expression analysis of multiple cardiac genes.

Erythropoietin signaling regulates heme biosynthesis.

Heme is required for survival of all cells, and in most eukaryotes, is produced through a series of eight enzymatic reactions. Although heme production is critical for many cellular processes, how it is coupled to cellular differentiation is unknown. Here, using zebrafish, murine, and human models, we show that erythropoietin (EPO) signaling, together with the GATA1 transcriptional target, AKAP10, regulates heme biosynthesis during erythropoiesis at the outer mitochondrial membrane. This integrated pathway culminates with the direct phosphorylation of the crucial heme biosynthetic enzyme, ferrochelatase (FECH) by protein kinase A (PKA). Biochemical, pharmacological, and genetic inhibition of this signaling pathway result in a block in hemoglobin production and concomitant intracellular accumulation of protoporphyrin intermediates. Broadly, our results implicate aberrant PKA signaling in the pathogenesis of hematologic diseases. We propose a unifying model in which the erythroid transcriptional program works in concert with post-translational mechanisms to regulate heme metabolism during normal development.

The Pu.1 target gene Zbtb11 regulates neutrophil development through its integrase-like HHCC zinc finger.

In response to infection and injury, the neutrophil population rapidly expands and then quickly re-establishes the basal state when inflammation resolves. The exact pathways governing neutrophil/macrophage lineage outputs from a common granulocyte-macrophage progenitor are still not completely understood. From a forward genetic screen in zebrafish, we identify the transcriptional repressor, ZBTB11, as critical for basal and emergency granulopoiesis. ZBTB11 sits in a pathway directly downstream of master myeloid regulators including PU.1, and TP53 is one direct ZBTB11 transcriptional target. TP53 repression is dependent on ZBTB11 cys116, which is a functionally critical, metal ion-coordinating residue within a novel viral integrase-like zinc finger domain. To our knowledge, this is the first description of a function for this domain in a cellular protein. We demonstrate that the PU.1-ZBTB11-TP53 pathway is conserved from fish to mammals. Finally, Zbtb11 mutant rescue experiments point to a ZBTB11-regulated TP53 requirement in development of other organs.

The Early Stages of Heart Development: Insights from Chicken Embryos.

The heart is the first functioning organ in the developing embryo and a detailed understanding of the molecular and cellular mechanisms involved in its formation provides insights into congenital malformations affecting its function and therefore the survival of the organism. Because many developmental mechanisms are highly conserved, it is possible to extrapolate from observations made in invertebrate and vertebrate model organisms to humans. This review will highlight the contributions made through studying heart development in avian embryos, particularly the chicken. The major advantage of chick embryos is their accessibility for surgical manipulation and functional interference approaches, both gain- and loss-of-function. In addition to experiments performed in ovo, the dissection of tissues for ex vivo culture, genomic, or biochemical approaches is straightforward. Furthermore, embryos can be cultured for time-lapse imaging, which enables tracking of fluorescently labeled cells and detailed analysis of tissue morphogenesis. Owing to these features, investigations in chick embryos have led to important discoveries, often complementing genetic studies in mice and zebrafish. As well as including some historical aspects, we cover here some of the crucial advances made in understanding early heart development using the chicken model.

The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability.

In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E-binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine.

Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria.

Mitochondrial iron is essential for the biosynthesis of heme and iron-sulfur ([Fe-S]) clusters in mammalian cells. In developing erythrocytes, iron is imported into the mitochondria by MFRN1 (mitoferrin-1, SLC25A37). Although loss of MFRN1 in zebrafish and mice leads to profound anemia, mutant animals showed no overt signs of porphyria, suggesting that mitochondrial iron deficiency does not result in an accumulation of protoporphyrins. Here, we developed a gene trap model to provide in vitro and in vivo evidence that iron regulatory protein-1 (IRP1) inhibits protoporphyrin accumulation. Mfrn1(+/gt);Irp1(-/-) erythroid cells exhibit a significant increase in protoporphyrin levels. IRP1 attenuates protoporphyrin biosynthesis by binding to the 5'-iron response element (IRE) of alas2 mRNA, inhibiting its translation. Ectopic expression of alas2 harboring a mutant IRE, preventing IRP1 binding, in Mfrn1(gt/gt) cells mimics Irp1 deficiency. Together, our data support a model whereby impaired mitochondrial [Fe-S] cluster biogenesis in Mfrn1(gt/gt) cells results in elevated IRP1 RNA-binding that attenuates ALAS2 mRNA translation and protoporphyrin accumulation.