2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

The New South Wales Sudden Cardiac Arrest Registry: A Data Linkage Cohort Study.

BACKGROUND: Sudden cardiac arrest (SCA) in young people aged 1 to 50 years often occurs with no presenting symptoms or risk factors prompting screening for cardiovascular disease prior to their cardiac arrest. Approximately 3,000 young Australians suffer from sudden cardiac death (SCD) each year, making this a major public health issue. However, there is significant variation in the way incidence is estimated resulting in discrepancy across reporting which impacts our ability to understand and prevent these devastating events. We describe the New South Wales (NSW) Sudden Cardiac Arrest Registry: a retrospective, data linkage study which will identify all SCAs in the young in NSW from 2009 through to June 2022. OBJECTIVE: To determine the incidence, demographic characteristics and causes of SCA in young people. We will develop an NSW-based registry that will contribute to a greater understanding of SCA including risk factors and outcomes. METHODS: The cohort will include all people who experience a SCA in the NSW community aged between 1 to 50 years. Cases will be identified using the following three datasets: the Out of Hospital Cardiac Arrest Register housed at NSW Ambulance, the NSW Emergency Department Data Collection, and the National Coronial Information System. Data from eight datasets will be collected, anonymised and linked for the entire cohort. Analysis will be undertaken and reported using descriptive statistics. CONCLUSIONS: The NSW SCA registry will be an important resource for the improved understanding of SCA and inform the widespread impacts it has on individuals, their families and society.

Adult Basic Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 22 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 5 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

High-affinity IgG antibodies develop naturally in Ig-knockout rats carrying germline human IgH/Igκ/Igλ loci bearing the rat CH region.

Mice transgenic for human Ig loci are an invaluable resource for the production of human Abs. However, such mice often do not yield human mAbs as effectively as conventional mice yield mouse mAbs. Suboptimal efficacy in delivery of human Abs might reflect imperfect interaction between the human membrane IgH chains and the mouse cellular signaling machinery. To obviate this problem, in this study we generated a humanized rat strain (OmniRat) carrying a chimeric human/rat IgH locus (comprising 22 human V(H)s, all human D and J(H) segments in natural configuration linked to the rat C(H) locus) together with fully human IgL loci (12 Vκs linked to Jκ-Cκ and 16 Vλs linked to Jλ-Cλ). The endogenous Ig loci were silenced using designer zinc finger nucleases. Breeding to homozygosity resulted in a novel transgenic rat line exclusively producing chimeric Abs with human idiotypes. B cell recovery was indistinguishable from wild-type animals, and human V(D)J transcripts were highly diverse. Following immunization, the OmniRat strain performed as efficiently as did normal rats in yielding high-affinity serum IgG. mAbs, comprising fully human variable regions with subnanomolar Ag affinity and carrying extensive somatic mutations, are readily obtainable, similarly to conventional mAbs from normal rats.

The effect of alternative methods of cardiopulmonary resuscitation - Cough CPR, percussion pacing or precordial thump - on outcomes following cardiac arrest. A systematic review.

BACKGROUND: Cardiopulmonary resuscitation (CPR) improves cardiac arrest survival. Cough CPR, percussion pacing and precordial thump have been reported as alternative CPR techniques. We aimed to summarise in a systematic review the effectiveness of these alternative CPR techniques. METHODS: We searched Ovid MEDLINE, EMBASE and the Cochrane Library on 24/08/2020. We included randomised controlled trials, observational studies and case series with five or more patients. Two reviewers independently reviewed title and abstracts to identify studies for full-text review, and reviewed bibliographies and 'related articles' (using PubMed) of full-texts for further eligible studies. We extracted data and performed risk-of-bias assessments on studies included in the systematic review. We summarised data in a narrative synthesis, and used GRADE to assess evidence certainty. RESULTS: We included 23 studies (cough CPR n = 4, percussion pacing n = 4, precordial thump n = 16; one study studied two interventions). Only two (both precordial thump) had a comparator group ('standard' CPR). For all techniques evidence certainty was very low. Available evidence suggests that precordial thump does not improve survival to hospital discharge in out-of-hospital cardiac arrest. The review did not find evidence that cough CPR or percussion pacing improve clinical outcomes following cardiac arrest. CONCLUSION: Cough CPR, percussion pacing and precordial thump should not be routinely used in established cardiac arrest. In specific inpatient, monitored settings cough CPR (in conscious patients) or percussion pacing may be attempted at the onset of a potential lethal arrhythmia. These must not delay standard CPR efforts in those who lose cardiac output. PROSPERO REGISTRATION NUMBER: CRD42019152925.

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

Intravenous vs. intraosseous administration of drugs during cardiac arrest: A systematic review.

AIM: To perform a systematic review of the literature on intravenous (IV) vs. intraosseous (IO) administration of drugs during cardiac arrest in order to inform an update of international guidelines. METHODS: The review was performed according to PRISMA guidelines and registered on PROSPERO. Medline, Embase and Evidence-Based Medicine Reviews were searched on December 17, 2019 for studies comparing IV to IO administration of drugs. The population included neonatal, paediatric, and adult patients with cardiac arrest. Two investigators reviewed each search for study relevance, extracted data, and assessed the risk of bias of individual studies. Meta-analyses were performed for studies without a critical risk of bias. Certainty of evidence was evaluated using GRADE. RESULTS: We included six observational studies comparing IV to IO administration of drugs and two randomized trials assessing the effect of specific drugs in subgroups related to IV vs. IO administration. All studies included adult out-of-hospital cardiac arrest patients. No studies were identified in neonatal or paediatric patients. The risk of bias for the observational studies was overall assessed as critical or serious, with confounding and selection bias being the primary sources of bias. The meta-analyses excluding studies with a critical risk of bias favoured IV access for all outcomes. Using GRADE, the certainty of evidence was judged at very low. Subgroup analyses of the two randomized trials demonstrated no statistically significant interactions between the route of access and study drugs on outcomes. However, these trials were underpowered to assess such interactions. CONCLUSIONS: We identified a limited number of studies comparing IV vs. IO administration of drugs during cardiac arrest. Pooled results from four observational studies favoured IV access with very low certainty of evidence. From the subgroup analyses of two randomized clinical trials, there was no statistically significant interaction between the route of access and study drug on outcomes.

Adult Basic Life Support: International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 20 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 3 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

Advanced airway management during adult cardiac arrest: A systematic review.

AIM: To systematically review the literature on advanced airway management during adult cardiac arrest in order to inform the International Liaison Committee of Resuscitation (ILCOR) consensus on science and treatment recommendations. METHODS: The review was performed according to PRISMA guidelines and registered on PROSPERO (CRD42018115556). We searched Medline, Embase, and Evidence-Based Medicine Reviews for controlled trials and observational studies published before October 30, 2018. The population included adult patients with cardiac arrest. Two investigators reviewed studies for relevance, extracted data, and assessed the risk of bias of individual studies. RESULTS: We included 78 observational studies and 11 controlled trials. Most of the observational studies and all of the controlled trials only included patients with out-of-hospital cardiac arrest. The risk of bias for individual observational studies was overall assessed as critical or serious, with confounding and selection bias being the primary sources of bias. Three of the controlled trials, all published in 2018, were powered for clinical outcomes with two comparing a supraglottic airway to tracheal intubation and one comparing bag-mask ventilation to tracheal intubation. All three trials had some concerns regarding risk of bias primarily due to lack of blinding and variable adherence to the protocol. Clinical and methodological heterogeneity across studies, for both the observational studies and the controlled trials, precluded any meaningful meta-analyses. CONCLUSIONS: We identified a large number of studies related to advanced airway management in adult cardiac arrest. Three recently published, large randomized trials in out-of-hospital cardiac arrest will help to inform future guidelines. Trials of advanced airway management during in-hospital cardiac arrest are lacking.

Human antibody production in transgenic animals.

Fully human antibodies from transgenic animals account for an increasing number of new therapeutics. After immunization, diverse human monoclonal antibodies of high affinity can be obtained from transgenic rodents, while large animals, such as transchromosomic cattle, have produced respectable amounts of specific human immunoglobulin (Ig) in serum. Several strategies to derive animals expressing human antibody repertoires have been successful. In rodents, gene loci on bacterial artificial chromosomes or yeast artificial chromosomes were integrated by oocyte microinjection or transfection of embryonic stem (ES) cells, while ruminants were derived from manipulated fibroblasts with integrated human chromosome fragments or human artificial chromosomes. In all strains, the endogenous Ig loci have been silenced by gene targeting, either in ES or fibroblast cells, or by zinc finger technology via DNA microinjection; this was essential for optimal production. However, comparisons showed that fully human antibodies were not as efficiently produced as wild-type Ig. This suboptimal performance, with respect to immune response and antibody yield, was attributed to imperfect interaction of the human constant region with endogenous signaling components such as the Igα/ß in mouse, rat or cattle. Significant improvements were obtained when the human V-region genes were linked to the endogenous CH-region, either on large constructs or, separately, by site-specific integration, which could also silence the endogenous Ig locus by gene replacement or inversion. In animals with knocked-out endogenous Ig loci and integrated large IgH loci, containing many human Vs, all D and all J segments linked to endogenous C genes, highly diverse human antibody production similar to normal animals was obtained.

Human antibody expression in transgenic rats: comparison of chimeric IgH loci with human VH, D and JH but bearing different rat C-gene regions.

Expression of human antibody repertoires in transgenic animals has been accomplished by introducing large human Ig loci into mice and, more recently, a chimeric IgH locus into rats. With human VH, D and JH genes linked to the rat C-region antibody expression was significantly increased, similar to wild-type levels not found with fully human constructs. Here we compare four rat-lines containing the same human VH-region (comprising 22 VHs, all Ds and all JHs in natural configuration) but linked to different rat CH-genes and regulatory sequences. The endogenous IgH locus was silenced by zinc-finger nucleases. After breeding, all lines produced exclusively chimeric human H-chain with near normal IgM levels. However, in two lines poor IgG expression and inefficient immune responses were observed, implying that high expression, class-switching and hypermutation are linked to optimal enhancer function provided by the large regulatory region at the 3' end of the IgH locus. Furthermore, exclusion of Cδ and its downstream interval region may assist recombination. Highly diverse IgG and immune responses similar to normal rats were identified in two strains carrying diverse and differently spaced C-genes.