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Summary: Background: Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. Methods: Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. Findings: The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). Interpretation: This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. Funding: This study was funded in part by Italian Ministry of Health-Current research IRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.

Introduction: Post-cardiac arrest brain injury (PCABI) is the primary determinant of clinical outcomes for patients who achieve return of spontaneous circulation after cardiac arrest (CA). There are limited neuroprotective therapies available to mitigate the acute pathophysiology of PCABI. Methods: Neuroprotection was one of six focus topics for the Wolf Creek XVII Conference held on June 14–17, 2023 in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of CA resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation, and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category. Results: Top 5 knowledge gaps included developing therapies for neuroprotection; improving understanding of the pathophysiology, mechanisms, and natural history of PCABI; deploying precision medicine approaches; optimizing resuscitation and CPR quality; and determining optimal timing for and duration of interventions. Top 5 barriers to translation included patient heterogeneity; nihilism & lack of knowledge about cardiac arrest; challenges with the translational pipeline; absence of mechanistic biomarkers; and inaccurate neuro-triage and neuroprognostication. Top 5 research priorities focused on translational research and trial optimization; addressing patient heterogeneity and individualized interventions; improving understanding of pathophysiology and mechanisms; developing mechanistic and outcome biomarkers across post-CA time course; and improving implementation of science and technology. Conclusion: This overview can serve as a guide to transform the care and outcome of patients with PCABI. Addressing these topics has the potential to improve both research and clinical care in the field of neuroprotection for PCABI.

Introduction: Cardiac arrest results in a high death rate if cardiopulmonary resuscitation and early defibrillation are not performed. Mortality is strongly linked to regulations, in terms of prevention and emergency–urgency system organization. In Italy, training of lay rescuers and the presence of defibrillators were recently made mandatory in schools. Our analysis aims to analyze Out-of-Hospital Cardiac Arrest (OHCA) events in pediatric patients (under 18 years old), to understand the epidemiology of this phenomenon and provide helpful evidence for policy-making. Methods: A retrospective observational analysis was conducted on the emergency databases of Lombardy Region, considering all pediatric OHCAs managed between 1 January 2016, and 31 December 2019. The demographics of the patients and the logistics of the events were statistically analyzed. Results: The incidence in pediatric subjects is 4.5 (95% CI 3.6–5.6) per 100,000 of the population. School buildings and sports facilities have relatively few events (1.9% and 4.4%, respectively), while 39.4% of OHCAs are preventable, being due to violent accidents or trauma, mainly occurring on the streets (23.2%). Conclusions: Limiting violent events is necessary to reduce OHCA mortality in children. Raising awareness and giving practical training to citizens is a priority in general but specifically in schools.

Although cardiopulmonary resuscitation (CPR) includes lifesaving maneuvers, it might be associated with a wide spectrum of iatrogenic injuries. Among these, acute lung injury (ALI) is frequent and yields significant challenges to post-cardiac arrest recovery. Understanding the relationship between CPR and ALI is determinant for refining resuscitation techniques and improving patient outcomes. This review aims to analyze the existing literature on ALI following CPR, emphasizing prevalence, clinical implications, and contributing factors. The review seeks to elucidate the pathogenesis of ALI in the context of CPR, assess the efficacy of CPR techniques and ventilation strategies, and explore their impact on post-cardiac arrest outcomes. CPR-related injuries, ranging from skeletal fractures to severe internal organ damage, underscore the complexity of managing post-cardiac arrest patients. Chest compression, particularly when prolonged and vigorous, i.e., mechanical compression, appears to be a crucial factor contributing to ALI, with the concept of cardiopulmonary resuscitation-associated lung edema (CRALE) gaining prominence. Ventilation strategies during CPR and post-cardiac arrest syndrome also play pivotal roles in ALI development. The recognition of CPR-related lung injuries, especially CRALE and ALI, highlights the need for research on optimizing CPR techniques and tailoring ventilation strategies during and after resuscitation.

Abstract Background Lightning strike is a rare but dramatic cause of injury. Patients admitted to intensive care units (ICUs) with lightning strike frequently have a high mortality and significant long-term morbidity related to a direct brain injury or induced cardiac arrest (CA). Case presentation A 50-year-old Caucasian man was admitted to our hospital after being struck by lightning resulting in immediate CA. Spontaneous circulation was initially restored, and the man was admitted to the ICU, but ultimately died while in hospital due to neurological injury. The computer tomography scan revealed a massive loss of grey-white matter differentiation at the fronto-temporal lobes bilaterally. Somatosensory-evoked potentials demonstrated bilateral absence of the cortical somatosensory N20-potential, and the electroencephalogram recorded minimal cerebral electrical activity. The patient died on day 10 and a post-mortem study revealed a widespread loss of neurons. Conclusion This case study illustrates severe brain injury caused by a direct lighting strike, with the patient presenting an extraordinary microscopic pattern of neuronal desertification.

Summary: Background: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. Methods: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. Findings: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18–4.90]). No adverse events were reported. Interpretation: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. Trial registration: NCT03237910. Funding: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.

Introduction: Data on out-of-hospital cardiac arrest (OHCA) is limited in Italy, and there has never been a comprehensive systematic appraisal of the available evidence. Therefore, this review aims to explore the incidence, characteristics, and outcome of OHCA in Italy. Methods: We systematically searched PubMed, Embase, Google Scholar, ResearchGate, and conference proceedings up to September 23, 2022. Studies investigating OHCA in Italy and reporting at least one outcome related to cardiac arrest were considered eligible. The primary outcome was survival at the longest follow-up available. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. A random-effects model proportion meta-analysis was performed to calculate the pooled outcomes with 95% confidence interval (CI). Results: We included 42 studies (43,042 patients) from 13 of the 20 Italian regions published between 1995 and 2022. Only five studies were deemed to be at low risk of bias. The overall average incidences of OHCA attended by emergency medical services and with resuscitation attempted were 86 (range: 10–190) and 55 (range: 6–108) per 100,000 populations per year, respectively. Survival at the longest follow-up available was 9.0% (95% CI, 6.7–12%; 30 studies and 15,195 patients) in the overall population, 25% (95% CI, 21–30%; 16 studies and 2,863 patients) among patients with shockable rhythms, 28% (95% CI, 20–37%; 8 studies and 1,292 patients) among the Utstein comparator group. Favourable neurological outcome was 5.0% (95% CI, 3.6–6.6%; 16 studies and 9,675 patients). Return of spontaneous circulation was achieved in 19% (95% CI, 16–23%; 40 studies and 30,875 patients) of cases. Bystanders initiated cardiopulmonary resuscitation in 26% (95% CI, 21–32%; 33 studies and 23,491 patients) of cases but only in 3.2% (95% CI, 1.9–4.9%; 9 studies and 8,508 patients) with an automated external defibrillator. The mean response time was 10.2 (95% CI, 8.9–11.4; 25 studies and 23,997 patients) minutes. Conclusions: Survival after OHCA in Italy occurred in one of every ten patients. Bystanders initiated cardiopulmonary resuscitation in only one-third of cases, rarely with a defibrillator. Different areas of the country collected data, but an essential part of the population was not included. There was high heterogeneity and large variation in outcomes results and reporting, limiting the confidence in the estimates of incidence and outcome. Creating and maintaining a nationwide registry is a priority.

Abstract Background Perioperative cardiac arrest is a rare complication with an incidence of around 1 in 1400 cases, but it carries a high burden of mortality reaching up to 70% at 30 days. Despite its specificities, guidelines for treatment of perioperative cardiac arrest are lacking. Gathering the available literature may improve quality of care and outcome of patients. Methods The PERIOPCA Task Force identified major clinical questions about the management of perioperative cardiac arrest and framed them into the therapy population [P], intervention [I], comparator [C], and outcome [O] (PICO) format. Systematic searches of PubMed, Embase, and the Cochrane Library for articles published until September 2020 were performed. Consensus-based treatment recommendations were created using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The strength of consensus among the Task Force members about the recommendations was assessed through a modified Delphi consensus process. Results Twenty-two PICO questions were addressed, and the recommendations were validated in two Delphi rounds. A summary of evidence for each outcome is reported and accompanied by an overall assessment of the evidence to guide healthcare providers. Conclusions The main limitations of our work lie in the scarcity of good quality evidence on this topic. Still, these recommendations provide a basis for decision making, as well as a guide for future research on perioperative cardiac arrest.

Abstract Primary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 16 pigs and left untreated for 12 min. During CPR, animals were randomized to receive epinephrine (30 µg/kg) with either esmolol (0.5 mg/kg) or saline (control). Pigs were then observed up to 96 h. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (47 ± 21 vs. 24 ± 10 mmHg at min 5, p

Cardiac arrest, one of the leading causes of death, accounts for numerous clinical studies published each year. This review summarizes the findings of all the randomized controlled clinical trials (RCT) on cardiac arrest published in the year 2022. The RCTs are presented according to the following categories: out-of- and in-hospital cardiac arrest (OHCA, IHCA) and post-cardiac arrest care. Interestingly, more than 80% of the RCTs encompassed advanced life support and post-cardiac arrest care, while no studies focused on the treatment of IHCA, except for one that, however, explored the temperature control after resuscitation in this population. Surprisingly, 9 out of 11 RCTs led to neutral results demonstrating equivalency between the newly tested interventions compared to current practice. One trial was negative, showing that oxygen titration in the immediate pre-hospital post-resuscitation period decreased survival compared to a more liberal approach. One RCT was positive and introduced new defibrillation strategies for refractory cardiac arrest. Overall, data from the 2022 RCTs discussed here provide a solid basis to generate new hypotheses to be tested in future clinical studies.

Background Brain injury and neurological deficit are consequences of cardiac arrest (CA), leading to high morbidity and mortality. Peripheral activation of the kynurenine pathway (KP), the main catabolic route of tryptophan metabolized at first into kynurenine, predicts poor neurological outcome in patients resuscitated after out‐of‐hospital CA. Here, we investigated KP activation in hippocampus and plasma of rats resuscitated from CA, evaluating the effect of KP modulation in preventing CA‐induced neurological deficit. Methods and Results Early KP activation was first demonstrated in 28 rats subjected to electrically induced CA followed by cardiopulmonary resuscitation. Hippocampal levels of the neuroactive metabolites kynurenine, 3‐hydroxy‐anthranilic acid, and kynurenic acid were higher 2 hours after CA, as in plasma. Further, 36 rats were randomized to receive the inhibitor of the first step of KP, 1‐methyl‐DL‐tryptophan, or vehicle, before CA. No differences were observed in hemodynamics and myocardial function. The CA‐induced KP activation, sustained up to 96 hours in hippocampus (and plasma) of vehicle‐treated rats, was counteracted by the inhibitor as indicated by lower hippocampal (and plasmatic) kynurenine/tryptophan ratio and kynurenine levels. 1‐Methyl‐DL‐tryptophan reduced the CA‐induced neurological deficits, with a significant correlation between the neurological score and the individual kynurenine levels, as well as the kynurenine/tryptophan ratio, in plasma and hippocampus. Conclusions These data demonstrate the CA‐induced lasting activation of the first step of the KP in hippocampus, showing that this activation was involved in the evolving neurological deficit. The degree of peripheral activation of KP may predict neurological function after CA.

Objectives: During the coronavirus disease 2019 pandemic, emergency medical services (EMSs) were among the most affected; in fact, there were delays in rescue and changes in time-dependent disease networks. The aim of the study is to understand the impact of COVID-19 on the time-dependent trauma network in the Lombardy region. Methods: A retrospective analysis on major trauma was performed by analysing all records saved in the EmMa database from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Age, gender, time to first emergency vehicle on scene and mission duration were collected. Results: In 2020, compared to 2019, there was a reduction in major trauma diagnoses in March and April, during the first lockdown, OR 0.59 (95% CI 0.49–0.70; p < 0.0001), and a reduction in road accidents and accidents at work, while injuries related to falls from height and violent events increased. There was no significant increase in the number of deaths in the prehospital setting, OR 1.09 (95% CI 0.73–1.30; p = 0.325). Conclusions: The COVID-19 pandemic has changed the epidemiology of major trauma, but in the Lombardy region there was no significant change in mortality in the out-of-hospital setting.

Objectives: The COVID-19 pandemic had a significant impact on emergency medical systems (EMS). Regarding the ST-elevation myocardial infarction (STEMI) dependent time network, however, there is little evidence linked to the post-pandemic phase regarding this issue. Such information could prove to be of pivotal importance regarding STEMI clinical management, especially pre-hospital clinical protocols such as fibrinolysis. Methods: A retrospective observational cohort study of all STEMI rescues recorded in the Lombardy EMS registry from the 1st of January 2019 to the 30th of December 2021. Results: Regarding the number of STEMI diagnoses, March 2020 (first pandemic wave in Italy) saw a reduction compared to March 2019 (OR 0.76 [0.60–0.93], p = 0.011). The average time of the entire mission increased to 63.1 min in 2021, reaching 64.7 min in 2020, compared with 57.7 min in 2019. The number of HUBs for STEMI patients saw a reduction, falling from 52 HUBs in the pre-pandemic phase to 13 HUBs during the first wave. Conclusions: During the pandemic phase, there was an increase in the transportation times of STEMI patients from home to the hospital. Such changes did not alter the clinical approach in the out-of-hospital phase. Indeed, the implementation of fibrinolysis was not required.

The noble gas argon (Ar) is a “biologically” active element and has been extensively studied preclinically for its organ protection properties. This work reviews all preclinical studies employing Ar and describes the clinical uses reported in literature, analyzing 55 pertinent articles found by means of a search on PubMed and Embase. Ventilation with Ar has been tested in different models of acute disease at concentrations ranging from 20% to 80% and for durations between a few minutes up to days. Overall, lesser cell death, smaller infarct size, and better functional recovery after ischemia have been repeatedly observed. Modulation of the molecular pathways involved in cell survival, with resulting anti-apoptotic and pro-survival effects, appeared as the determinant mechanism by which Ar fulfills its protective role. These beneficial effects have been reported regardless of onset and duration of Ar exposure, especially after cardiac arrest. In addition, ventilation with Ar was safe both in animals and humans. Thus, preclinical and clinical data support future clinical studies on the role of inhalatory Ar as an organ protector.

Background Ventilation with the noble gas argon (Ar) has shown neuroprotective and cardioprotective properties in different in vitro and in vivo models. Hence, the neuroprotective effects of Ar were investigated in a severe, preclinically relevant porcine model of cardiac arrest. Methods and Results Cardiac arrest was ischemically induced in 36 pigs and left untreated for 12 minutes before starting cardiopulmonary resuscitation. Animals were randomized to 4‐hour post‐resuscitation ventilation with: 70% nitrogen–30% oxygen (control); 50% Ar–20% nitrogen–30% oxygen (Ar 50%); and 70% Ar–30% oxygen (Ar 70%). Hemodynamic parameters and myocardial function were monitored and serial blood samples taken. Pigs were observed up to 96 hours for survival and neurological recovery. Heart and brain were harvested for histopathology. Ten animals in each group were successfully resuscitated. Ninety‐six‐hour survival was 60%, 70%, and 90%, for the control, Ar 50%, and Ar 70% groups, respectively. In the Ar 50% and Ar 70% groups, 60% and 80%, respectively, achieved good neurological recovery, in contrast to only 30% in the control group (P

Background: Endotoxemia causes endothelial dysfunction and microthrombosis, which are pathogenic mechanisms of coagulopathy and organ failure during sepsis. Simvastatin has potential anti-thrombotic effects on liver endothelial cells. We investigated the hemostatic changes induced by lipopolysaccharide (LPS) and explored the protective effects of simvastatin against liver vascular microthrombosis. Methods and results: We compared male Wistar rats exposed to LPS (5 mg/kg one i.p. dose) or saline in two experimental protocols—placebo (vehicle) and simvastatin (25 mg/kg die, orally, for 3 days before LPS). Morphological studies were performed by light- and electron-microscopy analyses to show intravascular fibrin deposition, vascular endothelial structure and liver damage. Peripheral- and organ-hemostatic profiles were analyzed using whole blood viscoelastometry by ROTEM, liver biopsy and western-blot/immunohistochemistry of thrombomodulin (TM), as well as immunohistochemistry of the von Willebrand factor (VWF). LPS-induced fibrin deposition and liver vascular microthrombosis were combined with a loss of sinusoidal endothelial TM expression and VWF-release. These changes were associated with parenchymal eosinophilia and necrosis. ROTEM analyses displayed hypo-coagulability in the peripheral blood that correlated with the degree of intrahepatic fibrin deposition (p < 0.05). Simvastatin prevented LPS-induced fibrin deposition by preserving TM expression in sinusoidal cells and completely reverted the peripheral hypo-coagulability caused by endotoxemia. These changes were associated with a significant reduction of liver cell necrosis without any effect on eosinophilia. Conclusions: Simvastatin preserves the antithrombotic properties of sinusoidal endothelial cells disrupted by LPS, deserving pharmacological properties to contrast sepsis-associated coagulopathy and hepatic failure elicited by endotoxemia

The identification of new treatments for primary pulmonary arterial hypertension (PAH) is a critical unmet need since there is no a definitive cure for this disease yet. Due to the complexity of PAH, a wide set of methods are necessary to assess the response to a pharmacological intervention. Thus, a rigorous protocol is crucial when experimental studies are designed. In the present experimental protocol, a stepwise approach was followed in a monocrotaline-induced PAH model in the rat, moving from the dose finding study of treatment compounds to the recognition of the onset of disease manifestation, in order to identify when to start a curative treatment. A complete multidimensional evaluation of treatment effects represented the last step. The primary study endpoint was the change in right ventricular systolic pressure after 14 days of treatment; echocardiographic and biohumoral markers together with heart and pulmonary arterial morphometric parameters were considered as secondary efficacy and/or safety endpoints and for the evaluation of the biologic coherence in the different results.

Abstract Background Spine fusion is a surgical procedure characterized by a significant perioperative bleeding, which often requires red blood cell (RBC) transfusion. Methods The incidence and the cost of RBC transfusion were evaluated in all patients undergoing elective surgery for spine fusion in our Institution, a high-volume center for spine surgery, over a period of 3 years. The analysis specifically addressed the RBC transfusion need in all the different spine fusion procedures (atlanto-axial, cervical, dorsal, lumbar, revisions) with the different surgical approaches (anterior, posterior). Results During the 3 years of observation, a total of 1.882 elective spine fusions were performed. More than half of the procedures (n = 964) were posterior lumbar fusions. Overall, 5% of the patients (n = 103) required RBC transfusion. The cervical fusions were the procedures with the lowest percentage of RBC need (0–5%), while the dorsal and the lumbar ones, with the anterior approach, represented the procedures with the highest rate of transfusion (29% and 25% respectively). More than 60 % of the RBC units were employed in the instance of posterior lumbar fusion, while a variable 1–10% of the units was used in each of the other procedures. The overall transfusion cost was of 46.000 euros, with a distribution of costs that paralleled the amount of units transfused for each procedure. Conclusions Several surgical and patient factors may contribute to the perioperative blood loss. An accurate patient blood management, may efficiently decrease transfusion requirements and ultimately healthcare costs.

Introduction: Early intervention of bystanders (the first links of the chain of survival) have been shown to improve survival and good neurological outcomes of patients suffering out-of-hospital cardiac arrest (OHCA). Many initiatives have been implemented to increase the engagement of communities in early basic life support (BLS) and cardiopulmonary resuscitation (CPR), especially of lay people with no duty to respond. A better knowledge of the most effective initiatives might help improve survival and health system organization. Aim of the scoping review: To assess the impact of specific interventions involving lay communities on bystander BLS rates and other consistent clinical outcomes, and to identify relevant knowledge gaps. Methods: This scoping review was part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation (ILCOR), and was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We performed a literature search using the PubMed, EMBASE, and Cochrane databases until 1 February 2021. The screening process was conducted based on predefined inclusion/exclusion criteria, and for each included study, we performed data extraction focusing on the type of intervention implemented, and the impact of these interventions on the specific OHCAs outcomes. Results: Our search strategy identified 19 eligible studies, originating mainly from the USA (47.4%) and Denmark (21%). The type of intervention included in 57.9% of cases was a community CPR training program, in 36.8% bundled interventions, and in 5.3% mass-media campaigns. The most commonly reported outcome for OHCAs was bystander CPR rate (94.7%), followed by survival to hospital discharge (36.8%), proportion of people trained (31.6%), survival to hospital discharge with good neurological outcome (21%), and Return of Spontaneous Circulation (10.5%). Community training programs and bundled interventions improved bystander CPR in most of the included studies. Conclusion: Based on the results of our scoping review, we identified the potential benefit of community initiatives, such as community training in BLS, even as part of bundled intervention, in order to improve bystander CPR rates and patient outcomes.

Introduction: The rapid use of an automated external defibrillator (AED) is crucial for increased survival after an out-of-hospital cardiac arrest (OHCA). Many factors could play a role in limiting the chance of an AED use. We aimed to verify the situation regarding AED legislation, the AED mapping system and first responders (FRs) equipped with an AED across European countries. Methods: We performed a survey across Europe entitled “European Study about AED Use by Lay Rescuers” (ENSURE), asking the national coordinators of the European Registry of Cardiac Arrest (EuReCa) program to complete it. Results: Nineteen European countries replied to the survey request for a population covering 128,297,955 inhabitants. The results revealed that every citizen can use an AED in 15 countries whereas a training certificate was required in three countries. In one country, only EMS personnel were allowed to use an AED. An AED mapping system and FRs equipped with an AED were available in only 11 countries. The AED use rate was 12–59% where AED mapping and FR systems were implemented, which was considerably higher than in other countries (0–7.9%), reflecting the difference in OHCA survival. Conclusions: Our survey highlighted a heterogeneity in AED legislation, AED mapping systems and AED use in Europe, which was reflected in different AED use and survival.

Target temperature management (TTM) in cardiac arrest (CA) survivors is recommended after hospital admission for its possible beneficial effects on survival and neurological outcome. Whether a lower target temperature (i.e., 32–34 °C) improves outcomes is unclear. We conducted a systematic review and meta-analysis on Pubmed and EMBASE to evaluate the effects on mortality and neurologic outcome of TTM at 32–34 °C as compared to controls (patients cared with “actively controlled” or “uncontrolled” normothermia). Results were analyzed via risk ratios (RR) and 95% confidence intervals (CI). Eight randomized controlled trials (RCTs) were included. TTM at 32–34 °C was compared to “actively controlled” normothermia in three RCTs and to “uncontrolled” normothermia in five RCTs. TTM at 32–34 °C does not improve survival as compared to normothermia (RR:1.06 (95%CI 0.94, 1.20), p = 0.36; I2 = 39%). In the subgroup analyses, TTM at 32–34 °C is associated with better survival when compared to “uncontrolled” normothermia (RR: 1.31 (95%CI 1.07, 1.59), p = 0.008) but shows no beneficial effects when compared to “actively controlled” normothermia (RR: 0.97 (95%CI 0.90, 1.04), p = 0.41). TTM at 32–34 °C does not improve neurological outcome as compared to normothermia (RR: 1.17 (95%CI 0.97, 1.41), p = 0.10; I2 = 60%). TTM at 32–34 °C increases the risk of arrhythmias (RR: 1.35 (95%CI 1.16, 1.57), p = 0.0001, I2 = 0%). TTM at 32–34 °C does not improve survival nor neurological outcome after CA and increases the risk of arrhythmias.

Background: The National Early Warning Score (NEWS) is an assessment scale of in-hospital patients’ conditions. The purpose of this study was to assess the appropriateness of a potential off-label use of NEWS by the emergency medical system (EMS) to facilitate the identification of critical patients and to trigger appropriate care in the pre-hospital setting. Methods: A single centre, longitudinal, prospective study was carried out between July and August 2020 in the EMS service of Bologna. Home patients with age ≥ 18 years old were included in the study. The exclusion criterion was the impossibility to collect all the parameters needed to measure NEWS. Results: A total of 654 patients were enrolled in the study. The recorded NEWS values increased along with the severity of dispatch priority code, the EMS return code, the emergency department triage code, and with patients’ age (r = 0.135; p = 0.001). The aggregated value of NEWS was associated with an increased risk of hospitalization (OR = 1.30 (1.17; 1.34); p < 0.0001). Conclusion: This study showed that the use of NEWS in the urgent and emergency care services can help patient assessment while not affecting EMS crew operation and might assist decision making in terms of severity-code assignment and resources utilization.

The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The prototype of the pentraxin family is C reactive protein (CRP), a widely-used biomarker in human pathologies with an inflammatory or infectious origin. Data so far describe PTX3 as a multifunctional protein acting as a functional ancestor of antibodies and playing a regulatory role in inflammation. Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and inflammation is crucial in promoting it. Data from animal models indicate that PTX3 can have cardioprotective and atheroprotective roles regulating inflammation. PTX3 has been investigated in several clinical settings as possible biomarker of CVD. Data collected so far indicate that PTX3 plasma levels rise rapidly in acute myocardial infarction, heart failure and cardiac arrest, reflecting the extent of tissue damage and predicting the risk of mortality.

Background Mechanical chest compression (CC) is currently suggested to deliver sustained high‐quality CC in a moving ambulance. This study compared the hemodynamic support provided by a mechanical piston device or manual CC during ambulance transport in a porcine model of cardiopulmonary resuscitation. Methods and Results In a simulated urban ambulance transport, 16 pigs in cardiac arrest were randomized to 18 minutes of mechanical CC with the LUCAS (n=8) or manual CC (n=8). ECG, arterial and right atrial pressure, together with end‐tidal CO2 and transthoracic impedance curve were continuously recorded. Arterial lactate was assessed during cardiopulmonary resuscitation and after resuscitation. During the initial 3 minutes of cardiopulmonary resuscitation, the ambulance was stationary, while then proceeded along a predefined itinerary. When the ambulance was stationary, CC‐generated hemodynamics were equivalent in the 2 groups. However, during ambulance transport, arterial and coronary perfusion pressure, and end‐tidal CO2 were significantly higher with mechanical CC compared with manual CC (coronary perfusion pressure: 43±4 versus 18±4 mmHg; end‐tidal CO2: 31±2 versus 19±2 mmHg, P

Proteomic technologies have identified 234 peptidases in plasma but little quantitative information about the proteolytic activity has been uncovered. In this study, the substrate profile of plasma proteases was evaluated using two nano-LC-ESI-MS/MS methods. Multiplex substrate profiling by mass spectrometry (MSP-MS) quantifies plasma protease activity in vitro using a global and unbiased library of synthetic peptide reporter substrates, and shotgun peptidomics quantifies protein degradation products that have been generated in vivo by proteases. The two approaches gave complementary results since they both highlight key peptidase activities in plasma including amino- and carboxypeptidases with different substrate specificity profiles. These assays provide a significant advantage over traditional approaches, such as fluorogenic peptide reporter substrates, because they can detect active plasma proteases in a global and unbiased manner, in comparison to detecting select proteases using specific reporter substrates. We discovered that plasma proteins are cleaved by endoproteases and these peptide products are subsequently degraded by amino- and carboxypeptidases. The exopeptidases are more active and stable in plasma and therefore were found to be the most active proteases in the in vitro assay. The protocols presented here set the groundwork for studies to evaluate changes in plasma proteolytic activity in shock.

Welcome to the journal of Burns & Trauma launched in 2013 and published by the prestigious Wolters Kluwer Health. We are grateful to promote a cultural challenge toward a new horizon in the field of translational research (TR). We enjoy to work together with the common objective to perform continuous medical education programs, exploring the methods in research, designing study, and to improve multidisciplinary and multiprofessional collaboration in the basic sciences and in the clinical trials. Defined narrowly, epistemology is the study of knowledge and justified belief. Epistemology is concerned with the following questions: What are the necessary and sufficient conditions of knowledge? What are its sources? What is its structure and what are its limits? More broadly, epistemology is about issues having to do with the creation and dissemination of knowledge in particular areas of inquiry as defined and revisiting at the beginning of the last decades. Translational medicine (TM) should meet the demands to maintain or expanding the biomedical workforce and education programs that attract and retain young people in the translational and biomedical sciences. With this present contributes, we invite the members of the editorial board of Burns & Trauma to encourage submitting, in a special section, their personal experience about the philosophy of "Translation research." If this has a chance, welcome to the researchers, clinicians, and the allied people for their decisive contributions to strengthen the importance of a common way about the principles and methods of basic and clinical research. TR and TM represent a dynamic entity making a link, a sort of bridge, "from bench to bedside", or from laboratory experiments through clinical trials to point-of-care patient applications. Epistemological pluralism is a critical point for conducting innovative, collaborative research which can lead to more successful integrated and successfully study, particularly important in the field of burns and trauma.

(1) Background: This study evaluated the perioperative red blood cell (RBC) transfusion need and determined predictors for transfusion in patients undergoing elective primary lumbar posterior spine fusion in a high-volume center for spine surgery. (2) Methods: Data from all patients undergoing spine surgery between 1 January 2014 and 31 December 2016 were reviewed. Patients’ demographics and comorbidities, perioperative laboratory results, and operative time were analyzed in relation to RBC transfusion. Multivariate logistic regression analysis was performed to identify the predictors of transfusion. (3) Results: A total of 874 elective surgeries for primary spine fusion were performed over the three years. Only 54 cases (6%) required RBC transfusion. Compared to the non-transfused patients, transfused patients were mainly female (p = 0.0008), significantly older, with a higher ASA grade (p = 0.0002), and with lower pre-surgery hemoglobin (HB) level and hematocrit (p < 0.0001). In the multivariate logistic regression, a lower pre-surgery HB (OR (95% CI) 2.84 (2.11–3.82)), a higher ASA class (1.77 (1.03–3.05)) and a longer operative time (1.02 (1.01–1.02)) were independently associated with RBC transfusion. (4) Conclusions: In the instance of elective surgery for primary posterior lumbar fusion in a high-volume center for spine surgery, the need for RBC transfusion is low. Factors anticipating transfusion should be taken into consideration in the patient’s pre-surgery preparation.