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Bernard J Smilde,1– 3 Esmée Botman,1– 3 Ruben D de Ruiter,1– 3 Jan Maerten Smit,2,4 Berend P Teunissen,2,5 Wouter D Lubbers,2,6 Lothar A Schwarte,2,6 Patrick Schober,2,6 E Marelise W Eekhoff1– 3 1Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Internal Medicine Section Endocrinology, Amsterdam, the Netherlands; 2Amsterdam UMC, Amsterdam Bone Center, Amsterdam, the Netherlands; 3Amsterdam Movement Sciences, Tissue Function and Regeneration, Amsterdam, the Netherlands; 4Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Plastic, Reconstructive and Hand Surgery, Amsterdam, the Netherlands; 5Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands; 6Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Anaesthesiology, Amsterdam, the NetherlandsCorrespondence: E Marelise W Eekhoff, Department of Internal Medicine section Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands, Tel +31 204440588, Email emw.eekhoff@amsterdamumc.nlAbstract: Fibrodysplasia ossificans progressiva (FOP), sometimes known as myositis ossificans progressiva, is an ultra-rare disease in which bone is formed in muscular tissue, tendons and ligaments. This is known as heterotopic ossification (HO). FOP is caused by a heterozygous mutation in the highly conserved ACVR1/ALK2 gene which affects about 1 in 1.5– 2 million individuals. At birth, patients with the predominant R206H mutation only exhibit a bilateral hallux valgus. During childhood, heterotopic bone formation develops in a typical pattern, affecting the axial muscles first before appendicular body parts are involved. HO can start spontaneously but is often elicited by soft tissue trauma or medical procedures. After soft tissue injury, an inflammatory process called a flare-up can start, followed by the formation of HO. HO leads to a limited range of motion, culminating in complete ankylosis of nearly all joints. As a result of HO surrounding the thorax, patients often suffer from thoracic insufficiency syndrome (TIS). TIS is the most common cause of a limited life expectancy for FOP patients, with a median life expectancy of 56 years. Management is focused on preventing soft-tissue injury that can provoke flare-ups. This includes prevention of iatrogenic damage by biopsies, intramuscular injections and surgery. Anti-inflammatory medication is often started when a flare-up occurs but has a poor basis of evidence. Several forms of potential treatment for FOP are being researched in clinical trials. Progression of the disease is monitored using CT and 18F-NaF PET/CT combined with functional assessments. Patients are regularly evaluated for frequently occurring complications such as restrictive lung disease. Here, we review the current management, monitoring and treatment of FOP.Keywords: fibrodysplasia ossificans progressiva, heterotopic ossification, activin A receptor type 1, treatment strategies

Maintenance or restoration of adequate tissue oxygenation is a main goal of anesthesiologic and intensive care patient management. Pathophysiological disturbances which interfere with aerobic metabolism may occur at any stage in the oxygen cascade from atmospheric gas to the mitochondria, and there is no single monitoring modality that allows comprehensive determination of "the oxygenation". To facilitate early detection of tissue hypoxia (or hyperoxia) and to allow a goal directed therapy targeted at the underlying problem, the anesthesiologist and intensive care physician require a thorough understanding of the numerous determinants that influence cellular oxygenation. This article reviews the basic physiology of oxygen uptake and delivery to tissues as well as the options to monitor determinants of oxygenation at different stages from the alveolus to the cell. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Adequate oxygenation of the gastrointestinal mucosa to preserve its barrier function is a basic objective in the prevention of multiple organ failure. Sustaining a positive airway pressure during the entire respiratory cycle remains a cornerstone in the therapeutic regimen to improve systemic oxygenation. Whereas increased systemic oxygenation during breathing continuous positive airway pressure has been shown, the impact of continuous positive airway pressure on regional oxygenation in the gastrointestinal tract has not yet been evaluated. We hypothesized that continuous positive airway pressure decreases microvascular oxygen saturation in gastric mucosa. DESIGN: Prospective, randomized study. SETTING: University department of anesthesiology. PARTICIPANTS: Twelve healthy volunteers. INTERVENTIONS: Incremental increases of continuous positive airway pressure (0, 5, and 10 cm H(2)O) and subsequent release of continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS: We continuously measured microvascular oxygen saturation in gastric mucosa by reflectance spectrophotometry. Systemic oxygen saturation, end-tidal Pco(2), respiratory rate, heart rate, and arterial blood pressure were obtained noninvasively. In every volunteer, microvascular oxygen saturation in gastric mucosa was reduced corresponding to the level of continuous positive airway pressure, although systemic variables, especially systemic oxygen saturation, did not change. Continuous positive airway pressure reduced microvascular oxygen saturation in gastric mucosa from 59 +/- 7% (baseline with 0 cm H(2)O continuous positive airway pressure, mean +/- sd) to 54 +/- 8% (p <.05) during 5 cm H(2)O continuous positive airway pressure and to 50 +/- 9% (p <.05) during 10 cm H(2)O continuous positive airway pressure, returning to 59 +/- 7% during spontaneous breathing with 0 cm H(2)O continuous positive airway pressure. End-tidal Pco(2), respiratory rate, as well as hemodynamic variables, remained stable. CONCLUSIONS: Reflectance spectrophotometry meticulously monitored changes in microvascular oxygen saturation in gastric mucosa during breathing continuous positive airway pressure. Microvascular oxygen saturation in gastric mucosa decreased with increasing levels of continuous positive airway pressure despite steady systemic variables. These results suggest that the impact of altering airway pressures on splanchnic oxygenation is not mirrored necessarily by concomitant changes in systemic circulation. Moreover, if these findings also apply to critically ill patients, monitoring microvascular oxygen saturation in gastric mucosa would be useful to further optimize the setting of ventilation variables. [ABSTRACT FROM AUTHOR]

Background: The Cormack-Lehane (CL) classification is broadly used to describe laryngeal view during direct laryngoscopy. This classification, however, has been validated by only a few studies reporting inconclusive data concerning its reliability. This discrepancy between widespread use and limited evidence prompted us to investigate the knowledge about the classification among anaesthesiologists and its intra- and inter-observer reliability.Methods: One hundred and twenty interviews were performed at a major European anaesthesia congress. Participants were interviewed about their general knowledge on grading systems to classify laryngeal view during laryngoscopy and were subsequently asked to define the grades of the CL classification. Inter- and intra-observer reliabilities were tested in 20 anaesthesiologists well familiar with the CL classification, who performed 100 laryngoscopies in a full-scale patient simulator.Results: Although 89% of interviewed subjects claimed to know a classification to describe laryngeal view during laryngoscopy, 53% were able to name a classification. When specifically asked about the CL classification, 74% of the interviewed subjects stated to know this classification, whereas 25% could define all four grades correctly. In the simulator-based part of the study, inter-observer reliability was fair with a kappa coefficient of 0.35 and intra-observer reliability was poor with a kappa of 0.15.Conclusions: The CL classification is poorly known in detail among anaesthesiologists and reproducibility even in subjects well familiar with this classification is limited. [ABSTRACT FROM AUTHOR]

Purpose: Trauma-related death is used as a parameter to evaluate the quality of trauma care and identify cases in which mortality could have been prevented under optimal trauma care conditions. The aim of this study was to identify trauma-related preventable death (TRPD) within our institute by an external expert panel and to evaluate inter-panel reliability., Methods: Trauma-related deaths between the 1st of January 2020 and the 1st of February 2022 at the Amsterdam University Medical Centre were identified. The severely injured patients (injury severity score ≥ 16) were enrolled for preventability analysis by an external multidisciplinary panel, consisting of a trauma surgeon, anaesthesiologist, emergency physician, neurosurgeon, and forensic physician. Case descriptions were provided, and panellists were asked to classify deaths as non-preventable, potentially preventable, and preventable. Agreements between the five observers were assessed by Fleiss kappa statistics., Results: In total 95 trauma-related deaths were identified. Of which 36 fatalities were included for analysis, the mean age was 55.3 years (± 24.5), 69.4% were male and 88.9% suffered blunt trauma. The mean injury severity score was 35.3 (± 15.3). Interobserver agreement within the external panel was moderate for survivability (Fleiss kappa 0.474) but low for categorical preventable death classification (Fleiss kappa 0.298). Most of the disagreements were between non-preventable or potentially preventable with care that could have been improved., Conclusion: Multidisciplinary panel review has a moderate inter-observer agreement regarding survivability and low agreement regarding categorical preventable death classification. A valid definition and classification of TRPD is required to improve inter-observer agreement and quality of trauma care., (© 2024. The Author(s).)

Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality in the developed world. Timely detection of cardiac arrest and prompt activation of emergency medical services (EMS) are essential, yet challenging. Automated cardiac arrest detection using sensor signals from smartwatches has the potential to shorten the interval between cardiac arrest and activation of EMS, thereby increasing the likelihood of survival., Objective: This cross-sectional survey study aims to investigate users' perspectives on aspects of continuous monitoring such as privacy and data protection, as well as other implications, and to collect insights into their attitudes toward the technology., Methods: We conducted a cross-sectional web-based survey in the Netherlands among 2 groups of potential users of automated cardiac arrest technology: consumers who already own a smartwatch and patients at risk of cardiac arrest. Surveys primarily consisted of closed-ended questions with some additional open-ended questions to provide supplementary insight. The quantitative data were analyzed descriptively, and a content analysis of the open-ended questions was conducted., Results: In the consumer group (n=1005), 90.2% (n=906; 95% CI 88.1%-91.9%) of participants expressed an interest in the technology, and 89% (n=1196; 95% CI 87.3%-90.7%) of the patient group (n=1344) showed interest. More than 75% (consumer group: n= 756; patient group: n=1004) of the participants in both groups indicated they were willing to use the technology. The main concerns raised by participants regarding the technology included privacy, data protection, reliability, and accessibility., Conclusions: The vast majority of potential users expressed a strong interest in and positive attitude toward automated cardiac arrest detection using smartwatch technology. However, a number of concerns were identified, which should be addressed in the development and implementation process to optimize acceptance and effectiveness of the technology., (© Wisse M F van den Beuken, Hans van Schuppen, Derya Demirtas, Vokko P van Halm, Patrick van der Geest, Stephan A Loer, Lothar A Schwarte, Patrick Schober. Originally published in JMIR Human Factors (https://humanfactors.jmir.org).)

Objective: Intoxicated patients are often encountered by emergency medical services (eg, in cases of recreational drug use, accidental ingestion, or inhalation of toxic substances or [attempted] suicide). Earlier research showed that a physician-staffed helicopter emergency medical service (P-HEMS) is regularly dispatched for intoxicated patients. However, it is still unclear if there is added value of P-HEMS compared with standard care provided by an ambulance crew. The aim of this study was to analyze the contribution of additional expertise and equipment that P-HEMS brings to the prehospital scene., Methods: In this retrospective study, we searched the database of the helicopter emergency medical service Lifeliner 1 serving the northwestern quadrant of the Netherlands for cases that involved intoxications from January 2013 to July 2020. Patients were included in this study if the primary reason for P-HEMS dispatch was intoxication. The types of intoxication were categorized as (illicit/recreational) drug related, suicide attempt, or accidental. The agents were categorized as stimulants, depressants, hallucinogenic, cannabinoids, and other substances such as bleach or insulin. Patient characteristics, vital signs, and the therapeutic interventions performed were recorded for analysis., Results: In our study period, P-HEMS was dispatched 23,878 times. Of these dispatches, a total of 259 cases were included for further analysis. The majority of patients were male (64.5%). Sixty-six patients (25.5%) had an intoxication of depressant agents alone, whereas 60 patients (23.2%) had an intoxication with a combination of agents. With 159 (61.4%) patients, the majority of cases involved recreational drug intoxications. Unintentional intoxications were treated in 27 (10.4%) patients, whereas 73 (28.2%) cases involved suicide attempts. In 159 patients (61.4%), prehospital endotracheal intubation was required; the vast majority was performed by the helicopter emergency medical service physician. Specific antidotes were administered in 56 (21.6%) of the cases., Conclusion: In this study, we found that P-HEMS crews might complement usual prehospital care by ambulance crews for patients with severe intoxications by bringing advanced skills (eg, airway management and specific antidotes) to the scene., Competing Interests: Declaration of Competing Interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/Objectives: Severe traumatic brain injury (TBI) is a frequent cause of morbidity and mortality worldwide. In the Netherlands, suspected TBI is a criterion for the dispatch of the physician-staffed helicopter emergency medical services (HEMS) which are operational 24 h per day. It is unknown if patient outcome is influenced by the time of day during which the incident occurs. Therefore, we investigated the association between the time of day of the prehospital treatment of severe TBI and 30-day mortality. Methods: A retrospective analysis of prospectively collected data from the BRAIN-PROTECT study was performed. Patients with severe TBI treated by one of the four Dutch helicopter emergency medical services were included and followed up to one year. The association between prehospital treatment during day- versus nighttime, according to the universal daylight period, and 30-day mortality was analyzed with multivariable logistic regression. A planned subgroup analysis was performed in patients with TBI with or without any other injury. Results: A total of 1794 patients were included in the analysis, of which 1142 (63.7%) were categorized as daytime and 652 (36.3%) as nighttime. Univariable analysis showed a lower 30-day mortality in patients with severe TBI treated during nighttime (OR 0.74, 95% CI 0.60-0.91, p = 0.004); this association was no longer present in the multivariable model (OR 0.82, 95% CI 0.59-1.16, p = 0.262). In a subgroup analysis, no association was found between mortality rates and the time of prehospital treatment in patients with combined injuries (TBI and any other injury). Patients with isolated TBI had a lower mortality rate when treated during nighttime than when treated during daytime (OR 0.51, 95% CI 0.34-0.76, p = 0.001). Within the whole cohort, daytime versus nighttime treatments were not associated with differences in functional outcome defined by the Glasgow Outcome Scale. Conclusions: In the overall study population, no difference was found in 30-day mortality between patients with severe TBI treated during day or night in the multivariable model. Patients with isolated severe TBI had lower mortality rates at 30 days when treated at nighttime.

Background: Severe traumatic brain injury is a leading cause of morbidity and mortality among young people around the world. Prehospital care focuses on the prevention and treatment of secondary brain injury and commonly includes tracheal intubation after induction of general anesthesia. The choice of induction agent in this setting is controversial. This study therefore investigated the association between the chosen induction medication etomidate versus S(+)-ketamine and the 30-day mortality in patients with severe traumatic brain injury who received prehospital airway management in the Netherlands., Methods: This study is a retrospective analysis of the prospectively collected observational data of the Brain Injury: Prehospital Registry of Outcomes, Treatments and Epidemiology of Cerebral Trauma (BRAIN-PROTECT) cohort study. Patients with suspected severe traumatic brain injury who were transported to a participating trauma center and who received etomidate or S(+)-ketamine for prehospital induction of anesthesia for advanced airway management were included. Statistical analyses were performed with multivariable logistic regression and inverse probability of treatment weighting analysis., Results: In total, 1,457 patients were eligible for analysis. No significant association between the administered induction medication and 30-day mortality was observed in unadjusted analyses (32.9% mortality for etomidate versus 33.8% mortality for S(+)-ketamine; P = 0.716; odds ratio, 1.04; 95% CI, 0.83 to 1.32; P = 0.711), as well as after adjustment for potential confounders (odds ratio, 1.08; 95% CI, 0.67 to 1.73; P = 0.765; and risk difference 0.017; 95% CI, -0.051 to 0.084; P = 0.686). Likewise, in planned subgroup analyses for patients with confirmed traumatic brain injury and patients with isolated traumatic brain injury, no significant differences were found. Consistent results were found after multiple imputations of missing data., Conclusions: The analysis found no evidence for an association between the use of etomidate or S(+)-ketamine as an anesthetic agent for intubation in patients with traumatic brain injury and mortality after 30 days in the prehospital setting, suggesting that the choice of induction agent may not influence the patient mortality rate in this population., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

A paradigm shift in traumatic cardiac arrest (TCA) perception switched the traditional belief of futility of TCA resuscitation to a more optimistic perspective, at least in selected cases. The goal of TCA resuscitation is to rapidly and aggressively treat the common potentially reversible causes of TCA. Advances in diagnostics and therapy in TCA are ongoing; however, they are not always translating into improved outcomes. Further research is needed to improve outcome in this often young and previously healthy patient population.

Cognitive impairment occurs in 40-65% of persons with multiple sclerosis and may be related to alterations in glutamatergic and GABAergic neurotransmission. Therefore, the aim of this study was to determine how glutamatergic and GABAergic changes relate to cognitive functioning in multiple sclerosis in vivo . Sixty persons with multiple sclerosis (mean age 45.5 ± 9.6 years, 48 females, 51 relapsing-remitting multiple sclerosis) and 22 age-matched healthy controls (45.6 ± 22.0 years, 17 females) underwent neuropsychological testing and MRI. Persons with multiple sclerosis were classified as cognitively impaired when scoring at least 1.5 standard deviations below normative scores on ≥30% of tests. Glutamate and GABA concentrations were determined in the right hippocampus and bilateral thalamus using magnetic resonance spectroscopy. GABA-receptor density was assessed using quantitative [ 11 C]flumazenil positron emission tomography in a subset of participants. Positron emission tomography outcome measures were the influx rate constant (a measure predominantly reflecting perfusion) and volume of distribution, which is a measure of GABA-receptor density. Twenty persons with multiple sclerosis (33%) fulfilled the criteria for cognitive impairment. No differences were observed in glutamate or GABA concentrations between persons with multiple sclerosis and healthy controls, or between cognitively preserved, impaired and healthy control groups. Twenty-two persons with multiple sclerosis (12 cognitively preserved and 10 impaired) and 10 healthy controls successfully underwent [ 11 C]flumazenil positron emission tomography. Persons with multiple sclerosis showed a lower influx rate constant in the thalamus, indicating lower perfusion. For the volume of distribution, persons with multiple sclerosis showed higher values than controls in deep grey matter, reflecting increased GABA-receptor density. When comparing cognitively impaired and preserved patients to controls, the preserved group showed a significantly higher volume of distribution in cortical and deep grey matter and hippocampus. Positive correlations were observed between both positron emission tomography measures and information processing speed in the multiple sclerosis group only. Whereas concentrations of glutamate and GABA did not differ between multiple sclerosis and control nor between cognitively impaired, preserved and control groups, increased GABA-receptor density was observed in preserved persons with multiple sclerosis that was not seen in cognitively impaired patients. In addition, GABA-receptor density correlated to cognition, in particular with information processing speed. This could indicate that GABA-receptor density is upregulated in the cognitively preserved phase of multiple sclerosis as a means to regulate neurotransmission and potentially preserve cognitive functioning., Competing Interests: M. Huiskamp receives research support from the Dutch MS Research Foundation. Prof. Dr. Killestein reports speaker and consulting fees and grants from Biogen, Celgene, Genzyme, Immunic, Merck, Novartis, Roche, Sanofi and Teva. Prof. Dr. van Berckel has received research support from EU-FP7, CTMM, ZonMw, NWO and Alzheimer Nederland. BvB has performed contract research for Rodin, IONIS, AVID, Eli Lilly, UCB, DIAN-TUI and Janssen. BvB was a speaker at a symposium organized by Springer Healthcare. BvB has a consultancy agreement with IXICO for the reading of PET scans. BvB is a trainer for GE. BvB only receives financial compensation from Amsterdam UMC. Prof. Dr. Geurts has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals; he has received research support from the Dutch MS Research Foundation, Ammodo, Eurostars-EUREKA, Biogen, Celgene/BMS, Merck, MedDay and Novartis. Prof. Dr. Hulst receives research support from Dutch MS Research Foundation, ZonMW, NWO, ATARA, Biogen, Celgene/BMS, Merck and Medday, serves as a consultant for Sanofi Genzyme, Merck BV, Biogen Idec, Roche and Novartis and is on the editorial board of Multiple Sclerosis Journal. Other authors report no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: Severe traumatic brain injury is a leading cause of mortality and morbidity, and these patients are frequently intubated in the prehospital setting. Cerebral perfusion and intracranial pressure are influenced by the arterial partial pressure of CO 2 and derangements might induce further brain damage. We investigated which lower and upper limits of prehospital end-tidal CO 2 levels are associated with increased mortality in patients with severe traumatic brain injury., Methods: The BRAIN-PROTECT study is an observational multicenter study. Patients with severe traumatic brain injury, treated by Dutch Helicopter Emergency Medical Services between February 2012 and December 2017, were included. Follow-up continued for 1 year after inclusion. End-tidal CO 2 levels were measured during prehospital care and their association with 30-day mortality was analyzed with multivariable logistic regression., Results: A total of 1776 patients were eligible for analysis. An L-shaped association between end-tidal CO 2 levels and 30-day mortality was observed (p = 0.01), with a sharp increase in mortality with values below 35 mmHg. End-tidal CO 2 values between 35 and 45 mmHg were associated with better survival rates compared to < 35 mmHg. No association between hypercapnia and mortality was observed. The odds ratio for the association between hypocapnia (< 35 mmHg) and mortality was 1.89 (95% CI 1.53-2.34, p < 0.001) and for hypercapnia (≥ 45 mmHg) 0.83 (0.62-1.11, p = 0.212)., Conclusion: A safe zone of 35-45 mmHg for end-tidal CO 2 guidance seems reasonable during prehospital care. Particularly, end-tidal partial pressures of less than 35 mmHg were associated with a significantly increased mortality., (© 2023. The Author(s).)

Objective: Patients with severe traumatic brain injury (TBI) are commonly intubated during prehospital treatment despite a lack of evidence that this is beneficial. Accumulating evidence even suggests that prehospital intubation may be hazardous, in particular when performed by inexperienced EMS clinicians. To expand the limited knowledge base, we studied the relationship between prehospital intubation and hospital mortality in patients with severe TBI in a large Dutch trauma database. We specifically hypothesized that the relationship differs depending on whether a physician-based emergency medical service (EMS) was involved in the treatment, as opposed to intubation by paramedics., Methods: A retrospective analysis was performed using the Dutch Nationwide Trauma Registry that includes all trauma patients in the Netherlands who are admitted to any hospital with an emergency department. All patients treated for severe TBI (Head Abbreviated Injury Scale score ≥4) between January 2015 and December 2019 were selected. Multivariable logistic regression was used to assess the relationship between prehospital intubation and mortality while adjusting for potential confounders. An interaction term between prehospital intubation and the involvement of physician-based EMS was added to the model. Complete case analysis as well as multiple imputation were performed., Results: 8946 patients (62% male, median age 63 years) were analyzed. The hospital mortality was 26.4%. Overall, a relationship between prehospital intubation and higher mortality was observed (complete case: OR 1.86, 95% CI 1.35-2.57, p  < 0.001; multiple imputation: OR 1.92, 95% CI 1.56-2.36, p  < 0.001). Adding the interaction revealed that the relationship of prehospital intubation may depend on whether physician-based EMS is involved in the treatment (complete case: p  = 0.044; multiple imputation: p  = 0.062). Physician-based EMS involvement attenuated but did not completely remove the detrimental association between prehospital intubation and mortality., Conclusion: The data do not support the common practice of prehospital intubation. The effect of prehospital intubation on mortality might depend on EMS clinician experience, and it seems prudent to involve prehospital personnel well proficient in prehospital intubation whenever intubation is potentially required. The decision to perform prehospital intubation should not merely be based on the largely unsupported dogma that it is generally needed in severe TBI, but should rather individually weigh potential benefits and harms.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality. Immediate detection and treatment are of paramount importance for survival and good quality of life. The first link in the 'chain of survival' after OHCA - the early recognition and alerting of emergency medical services - is at the same time the weakest link as it entirely depends on witnesses. About one half of OHCA cases are unwitnessed, and victims of unwitnessed OHCA have virtually no chance of survival with good neurologic outcome. Also in case of a witnessed cardiac arrest, alerting of emergency medical services is often delayed for several minutes. Therefore, a technological solution to automatically detect cardiac arrests and to instantly trigger an emergency response has the potential to save thousands of lives per year and to greatly improve neurologic recovery and quality of life in survivors. The HEART-SAFE consortium, consisting of two academic centres and three companies in the Netherlands, collaborates to develop and implement a technical solution to reliably detect OHCA based on sensor signals derived from commercially available smartwatches using artificial intelligence. In this manuscript, we describe the rationale, the envisioned solution, as well as a protocol outline of the work packages involved in the development of the technology., Competing Interests: Beat Nideröst is CTO of 111b.v., Tom A. Kooy is International Business Developer at Stan b.v., Steve Thijssen is Co-Founder of Wavy Assistant b.v. All three companies are involved in the development of the proposed technology within the HEART-SAFE consortium. Hans van Schuppen reports grants to his institution from the Zoll Foundation and Stryker Emergency Care, both outside the submitted work., (© 2022 The Author(s).)

Study Objective: Rising patient numbers, with increasing complexity, challenge the sustainability of the current preoperative process. We evaluated whether an electronic screening application can distinguish patients that need a preoperative consultation from low-risk patients that can be first seen on the day of surgery., Design: Prospective cohort study., Setting: Preoperative clinic of a tertiary academic hospital., Patients: 1395 adult patients scheduled for surgery or procedural sedation., Interventions: We assessed a novel electronic preoperative screening application which consists of a questionnaire with a maximum of 185 questions regarding the patient's medical history and current state of health. The application provides an extensive health report, including an American Society of Anesthesiologists physical status (ASA-PS) classification and a recommendation for either consultation by an anesthesiologist at the preoperative clinic or approval for screening on the day of surgery., Measurements: The recommendation of the electronic screening system was compared with the regular preoperative assessment using measures of diagnostic accuracy and agreement. Secondary outcomes included ASA-PS classification, patient satisfaction, and the anesthesiologists' opinion on the completeness and quality of the screening report., Results: Sensitivity to detect patients who needed additional consultation was 97.5% (95%CI 91.2-99.7) and the negative likelihood ratio was 0.08 (95%CI 0.02-0.32). 407 (29.2%) patients were approved for surgery by both electronic screening and anesthesiologist. In 909 (65.2%) cases, the electronic screening system recommended further consultation while the anesthesiologist approved the patient (specificity 30.9% (95%CI 28.4-33.5); poor level of agreement (ĸ = 0.04)). Agreement regarding ASA-PS classification scores was weak (ĸ = 0.48). The majority of patients (78.0%) felt positive about electronic screening replacing the regular preoperative assessment., Conclusions: Electronic screening can reliably identify patients who can have their first contact with an anesthesiologist on the day of surgery, potentially allowing a major proportion of patients to safely bypass the preoperative clinic., Competing Interests: Declaration of Competing Interest The authors declare no conflicting interests. E-POS® software was provided free of charge by Novacair (Leiden, the Netherlands), and the CEO of Novacair is staff anesthesiologist in the same institution as the authors. Novacair had no role in the design, conduct, analysis, and interpretation of the study, or the decision to publish., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Traumatic brain injury (TBI) is a leading cause of trauma-related deaths, and pharmacologic interventions to limit intracranial bleeding should improve outcomes. Tranexamic acid reduces mortality in injured patients with major systemic bleeding, but the effects of antifibrinolytic drugs on outcomes after TBI are less clear. We therefore summarize recent evidence to guide clinicians on when (not) to use antifibrinolytic drugs in TBI patients., Recent Findings: Tranexamic acid is the only antifibrinolytic drug that has been studied in patients with TBI. Several recent studies failed to conclusively demonstrate a benefit on survival or neurologic outcome. A large trial with more than 12 000 patients found no significant effect of tranexamic acid on head-injury related death, all-cause mortality or disability across the overall study population, but observed benefit in patients with mild to moderate TBI. Observational evidence signals potential harm in patients with isolated severe TBI., Summary: Given that the effect of tranexamic acid likely depends on a variety of factors, it is unlikely that a 'one size fits all' approach of administering antifibrinolytics to all patients will be helpful. Tranexamic acid should be strongly considered in patients with mild to moderate TBI and should be avoided in isolated severe TBI., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients with non-small cell lung cancer (NSCLC) driven by activating epidermal growth factor receptor (EGFR) mutations are best treated with therapies targeting EGFR, i.e., tyrosine kinase inhibitors (TKI). Radiolabeled EGFR-TKI and PET have been investigated to study EGFR-TKI kinetics and its potential role as biomarker of response in NSCLC patients with EGFR mutations (EGFRm). In this study we aimed to compare the biodistribution and kinetics of three different EGFR-TKI, i.e., 11 C-erlotinib, 18 F-afatinib and 11 C-osimertinib., Methods: Data of three prospective studies and 1 ongoing study were re-analysed; data from thirteen patients (EGFRm) were included for 11 C-erlotinib, seven patients for 18 F-afatinib (EGFRm and EGFR wild type) and four patients for 11 C-osimertinib (EGFRm). From dynamic and static scans, SUV and tumor-to-blood (TBR) values were derived for tumor, lung, spleen, liver, vertebra and, if possible, brain tissue. AUC values were calculated using dynamic time-activity-curves. Parent fraction, plasma-to-blood ratio and SUV values were derived from arterial blood data. Tumor-to-lung contrast was calculated, as well as (background) noise to assess image quality., Results: 11 C-osimertinib showed the highest SUV and TBR (AUC) values in nearly all tissues. Spleen uptake was notably high for 11 C-osimertinib and to a lesser extent for 18 F-afatinib. For EGFRm, 11 C-erlotinib and 18 F-afatinib demonstrated the highest tumor-to-lung contrast, compared to an inverse contrast observed for 11 C-osimertinib. Tumor-to-lung contrast and spleen uptake of the three TKI ranked accordingly to the expected lysosomal sequestration., Conclusion: Comparison of biodistribution and tracer kinetics showed that 11 C-erlotinib and 18 F-afatinib demonstrated the highest tumor-to-background contrast in EGFRm positive tumors. Image quality, based on contrast and noise analysis, was superior for 11 C-erlotinib and 18 F-afatinib (EGFRm) scans compared to 11 C-osimertinib and 18 F-afatinib (EGFR wild type) scans.

Objective: A thorough understanding of the epidemiology, patient characteristics, trauma mechanisms, and current outcomes among patients with severe traumatic brain injury (TBI) is important as it may inform potential strategies to improve prehospital emergency care. The aim of this study is to describe the prehospital epidemiology, characteristics and outcome of (suspected) severe TBI in the Netherlands., Methods: The BRAIN-PROTECT study is a prospective observational study on prehospital management of patients with severe TBI in the Netherlands. The study population comprised all consecutive patients with clinical suspicion of TBI and a prehospital GCS score ≤ 8, who were managed by one of the 4 Helicopter Emergency Medical Services (HEMS). Patients were followed-up in 9 trauma centers until 1 year after injury. Planned sub-analyses were performed for patients with "confirmed" and "isolated" TBI., Results: Data from 2,589 patients, of whom 2,117 (81.8%) were transferred to a participating trauma center, were analyzed. The incidence rate of prehospitally suspected and confirmed severe TBI were 3.2 (95% CI: 3.1;3.4) and 2.7 (95% CI: 2.5;2.8) per 100,000 inhabitants per year, respectively. Median patient age was 46 years, 58.4% were involved in traffic crashes, of which 37.4% were bicycle related. 47.6% presented with an initial GCS of 3. The median time from HEMS dispatch to hospital arrival was 54 minutes. The overall 30-day mortality was 39.0% (95% CI: 36.8;41.2)., Conclusion: This article summarizes the prehospital epidemiology, characteristics and outcome of severe TBI in the Netherlands, and highlights areas in which primary prevention and prehospital care can be improved.

In helicopter emergency medical services, HEMS, coagulopathy presents both in trauma (e.g. consumption of coagulation factors) and non-trauma cases (e.g. anticoagulant use). Therefore, in HEMS coagulation measurements appear promising and Prothrombin Time (PT) and derived INR are attractive variables herein. We tested the feasibility of prehospital PT/INR coagulation measurements in HEMS. This study was performed at the Dutch HEMS, using a portable blood analyzer (i-Stat®1, Abbott). PT/INR measurements were performed on (hemodiluted) author's blood, and both trauma- and non-trauma HEMS patients. Device-related benefits of the i-Stat PT/INR system were portability, speed and ease of handling. Limitations included a rather narrow operational temperature range (16-30 °C). PT/INR measurements (n = 15) were performed on hemodiluted blood, and both trauma and non-trauma patients. The PT/INR results confirmed effects of hemodilution and anticoagulation, however, most measurement results were in the normal INR-range (0.9-1.2). We conclude that prehospital PT/INR measurements, although with limitations, are feasible in HEMS operations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Sorafenib leads to clinical benefit in a subgroup of patients, whereas all are exposed to potential toxicity. Currently, no predictive biomarkers are available. The purpose of this study was to evaluate whether 11 C-sorafenib and 15 O-H 2 O PET have potential to predict treatment efficacy. Methods: In this prospective exploratory study, 8 patients with advanced solid malignancies and an indication for sorafenib treatment were included. Microdose 11 C-sorafenib and perfusion 15 O-H 2 O dynamic PET scans were performed before and after 2 wk of sorafenib therapy. The main objective was to assess whether tumor 11 C-sorafenib uptake predicts sorafenib concentrations during therapy in corresponding tumor biopsy samples measured with liquid chromatography tandem mass spectrometry. Secondary objectives included determining the association of 11 C-sorafenib PET findings, perfusion 15 O-H 2 O PET findings, and sorafenib concentrations after therapeutic dosing with response. Results: 11 C-sorafenib PET findings did not predict sorafenib concentrations in tumor biopsy samples during therapy. In addition, sorafenib plasma and tumor concentrations were not associated with clinical outcome in this exploratory study. Higher 11 C-sorafenib accumulation in tumors at baseline and day 14 of treatment showed an association with poorer prognosis and correlated with tumor perfusion (Spearman correlation coefficient = 0.671, P = 0.020). Interestingly, a decrease in tumor perfusion measured with 15 O-H 2 O PET after only 14 d of therapy showed an association with response, with a decrease in tumor perfusion of 56% ± 23% (mean ± SD) versus 18% ± 32% in patients with stable and progressive disease, respectively. Conclusion: Microdose 11 C-sorafenib PET did not predict intratumoral sorafenib concentrations after therapeutic dosing, but the association between a decrease in tumor perfusion and clinical benefit warrants further investigation., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: The SARS-CoV-2 virus has disrupted global and local medical supply chains. To combat the spread of the virus and prevent an uncontrolled outbreak with limited resources, national lockdown protocols have taken effect in the Netherlands since March 13 th , 2020. The aim of this study was to describe the incidence, type and characteristics of HEMS and HEMS-ambulance 'Lifeliner 1' dispatches during the initial phase of the COVID-19 pandemic compared to the same period one year prior., Methods: A retrospective review of all HEMS and HEMS-ambulance 'Lifeliner 1' dispatches was performed from the start of Dutch nationwide lockdown orders from March 13th until May 13th, 2020 and the corresponding period one year prior. Dispatch-, operational-, patient-, injury-, and on-site treatment characteristics were extracted for analysis. In addition, the rate of COVID-19 positively tested HEMS personnel and the time physicians were unable to take call was described., Results: During the initial phase of the COVID-19 pandemic, the HEMS and HEMS-ambulance was requested in 528 cases. One year prior, a total of 620 requests were received. The HEMS (helicopter and ambulance) was cancelled after deployment in 56.4% of the COVID-19 cohort and 50.7% of the historical cohort (P = 0.05). Incident location type did not differ between the two cohorts, specifically, there was no significant difference in the number of injuries that occurred at home in pandemic versus non-pandemic circumstances. Besides a decrease in the number of falls, the distribution of mechanisms of injury remained similar during the COVID-19 study period. There was no difference in self-inflicted injuries observed. Prehospital interventions remained similar during the COVID-19 pandemic compared to one year prior. Specifically, prehospital intubation did not differ between the two cohorts. The rate of COVID-19 positively tested HEMS personnel was 23.1%. Physicians who tested positive were unable to take call for a mean of 25 days (range 8-53)., Conclusion: A decrease in the number of deployments and increase in the number of cancelled missions was observed during the COVID-19 study period. No major differences in operational- and injury characteristics were found for HEMS and HEMS-ambulance dispatches between the initial phase of the COVID-19 pandemic in the Netherlands and the same period one year prior. These findings highlight the importance of continued operability of the HEMS, even during pandemic circumstances., Level of Evidence: III, retrospective comparative study.

Objective: The Extended Glasgow Outcome Scale (GOS-E) is used for objective assessment of functional outcome in traumatic brain injury (TBI). In situations where face-to-face contact is not feasible, telephonic assessment of the GOS-E might be desirable. The aim of this study is to assess the level of agreement between face-to-face and telephonic assessment of the GOS-E., Setting: Multicenter study in 2 Dutch University Medical Centers. Inclusion was performed in the outpatient clinic (face-to-face assessment, by experienced neurologist), followed by assessment via telephone of the GOS-E after ±2 weeks (by trained researcher)., Participants: Patients ±6 months after TBI., Design: Prospective validation study., Main Measures: Interrater agreement of the GOS-E was assessed with Cohen's weighted κ., Results: From May 2014 until March 2018, 50 patients were enrolled; 54% were male (mean age 49.1 years). Median time between trauma and in-person GOS-E examination was 158 days and median time between face-to-face and telephonic GOS-E was 15 days. The quadratic weighted κ was 0.79. Sensitivity analysis revealed a quadratic weighted κ of 0.77, 0.78, and 0.70 for moderate-severe, complicated mild, and uncomplicated mild TBI, respectively., Conclusion: No disagreements of more than 1 point on the GOS-E were observed, with the κ value representing good or substantial agreement. Assessment of the GOS-E via telephone is a valid alternative to the face-to-face interview when in-person contact is not feasible., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Non-small cell lung cancer (NSCLC) tumors harboring common (exon19del, L858R) and uncommon (e.g. G719X, L861Q) activating epidermal growth factor receptor (EGFR) mutations are best treated with EGFR tyrosine kinase inhibitors (TKI) such as the first-generation EGFR TKI erlotinib, second-generation afatinib or third-generation osimertinib. However, identifying these patients through biopsy is not always possible. Therefore, our aim was to evaluate whether 18 F-afatinib PET/CT could identify patients with common and uncommon EGFR mutations. Furthermore, we evaluated the relation between tumor 18 F-afatinib uptake and response to afatinib therapy., Materials and Methods: 18 F-afatinib PET/CT was performed in 12 patients: 6 EGFR wild type (WT), 3 EGFR common and 3 EGFR uncommon mutations. Tumor uptake of 18 F-afatinib was quantified using TBR&#95;WB 60-90 (tumor-to-whole blood activity ratio 60-90 min post-injection) for each tumor. Response was quantified per lesion using percentage of change (PC): [(response measurement (RM)-baseline measurement (BM))/BM]×100. Statistical analyses were performed using t-tests, correlation plots and sensitivity/specificity analysis., Results: Twenty-one tumors were identified. Injected dose was 348 ± 31 MBq. Group differences were significant between WT versus EGFR (common and uncommon) activating mutations (p = 0.03). There was no significant difference between EGFR common versus uncommon mutations (p = 0.94). A TBR&#95;WB 60-90 cut-off value of 6 showed the best relationship with response with a sensitivity of 70 %, a specificity of 100 % and a positive predictive value of 100 %., Conclusion: 18 F-afatinib uptake was higher in tumors with EGFR mutations (common and uncommon) compared to WT. Furthermore, a TBR&#95;WB 60-90 cut-off of 6 was found to best predict response to therapy. 18 F-afatinib PET/CT could provide a means to identify EGFR mutation positive patients who benefit from afatinib therapy., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: For decades, Helicopter Emergency Medical Services (HEMS) contribute greatly to prehospital patient care by performing advanced medical interventions on-scene. Unnecessary dispatches, resulting in cancellations, cause these vital resources to be temporarily unavailable and generate additional costs. A previous study showed a cancellation rate of 43.5% in our trauma region. However, little recent data about cancellation rates and reasons exist, despite revision of dispatch protocols. This study examines the current cancellation rate in our trauma region over a six-year period. Additionally, cancellation reasons are evaluated per type of dispatch and initial incident report, upon which HEMS is dispatched., Methods: This retrospective study analyzed the data of the Dutch HEMS Lifeliner 1 (North-West region of the Netherlands, covering a population of 5 million inhabitants), analyzing all subsequent cases between April 1st 2013 and April 1st 2019. Patient characteristics, type of dispatch (primary; based on dispatcher criteria versus secondary, as judged by the first ambulance team on site), initial incident report received by the EMS dispatch center, and information regarding day- or nighttime dispatches were collected. In case of cancellation, cancel rate and reason per type of dispatch and initial incident report were assessed., Results: In total, 18,638 dispatches were included. HEMS was canceled in 54.5% (95% CI 53.8-55.3%) of cases. The majority of canceled dispatches (76.1%) were canceled because respiratory, hemodynamic, and neurologic parameters were stable. Dispatches simultaneously activated with EMS (primary dispatch) were canceled in 58.3%, compared to 15.1% when HEMS assistance was requested by EMS based on their findings on-scene (secondary dispatch). A cancellation rate of 54.6% was found in trauma related dispatches (n = 12,148), compared to 52.2% in non-trauma related dispatches (n = 5378). Higher cancellation rates exceeding 60% were observed in the less common dispatch categories, e.g., anaphylaxis (66.3%), unknown incident report (66.0%), assault with a blunt object (64.1%), obstetrics (62.8%), and submersion (61.9%)., Conclusion: HEMS cancellations are increased, compared to previous research in our region. Yet, the cancellations are acceptable as the effect on HEMS' unavailbility remains minimized. Focus should be on identifying the patient in need of HEMS care while maintaining overtriage rates low. Continuous evaluation of HEMS triage is important, and dispatch criteria should be adjusted if necessary.

Importance: The development and expansion of intracranial hematoma are associated with adverse outcomes. Use of tranexamic acid might limit intracranial hematoma formation, but its association with outcomes of severe traumatic brain injury (TBI) is unclear., Objective: To assess whether prehospital administration of tranexamic acid is associated with mortality and functional outcomes in a group of patients with severe TBI., Design, Setting, and Participants: This multicenter cohort study is an analysis of prospectively collected observational data from the Brain Injury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma (BRAIN-PROTECT) study in the Netherlands. Patients treated for suspected severe TBI by the Dutch Helicopter Emergency Medical Services between February 2012 and December 2017 were included. Patients were followed up for 1 year after inclusion. Data were analyzed from January 10, 2020, to September 10, 2020., Exposures: Administration of tranexamic acid during prehospital treatment., Main Outcomes and Measures: The primary outcome was 30-day mortality. Secondary outcomes included mortality at 1 year, functional neurological recovery at discharge (measured by Glasgow Outcome Scale), and length of hospital stay. Data were also collected on demographic factors, preinjury medical condition, injury characteristics, operational characteristics, and prehospital vital parameters., Results: A total of 1827 patients were analyzed, of whom 1283 (70%) were male individuals and the median (interquartile range) age was 45 (23-65) years. In the unadjusted analysis, higher 30-day mortality was observed in patients who received prehospital tranexamic acid (odds ratio [OR], 1.34; 95% CI, 1.16-1.55; P < .001), compared with patients who did not receive prehospital tranexamic acid. After adjustment for confounders, no association between prehospital administration of tranexamic acid and mortality was found across the entire cohort of patients. However, a substantial increase in the odds of 30-day mortality persisted in patients with severe isolated TBI who received prehospital tranexamic acid (OR, 4.49; 95% CI, 1.57-12.87; P = .005) and after multiple imputations (OR, 2.05; 95% CI, 1.22-3.45; P = .007)., Conclusions and Relevance: This study found that prehospital tranexamic acid administration was associated with increased mortality in patients with isolated severe TBI, suggesting the judicious use of the drug when no evidence for extracranial hemorrhage is present.

Abstract: No Abstract., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology.)

Purpose: Purpose of this report is to describe the feasibility of lingual pulse oximetry and lingual near-infrared spectroscopy (NIRS) in a COVID-19 patient to assess lingual tissue viability after several days of mechanical ventilation in the prone position., Materials & Methods: In a COVID-19 ICU-patient, the tongue became grotesquely swollen, hardened and protruding from the oral cavity after 20 h of mechanical ventilation uninterrupted in the prone position. To assess the doubtful viability of the tongue, pulse-oximetric hemoglobin O 2 -saturation (SpO 2 ; Nellcor, OxiMax MAX-NI, Covidien, MA, USA) and NIRS-based, regional tissue O 2 -saturation measurements (rSO 2 ; SenSmart, Nonin, MN, USA) were performed at the tongue., Results: At the tongue, regular pulse-oximetric waveforms with a pulse-oximetric hemoglobin O 2 -saturation (SpO 2 ) of 88% were recorded, i.e. only slightly lower than the SpO 2 reading at the extremities at that time (90%). Lingual NIRS-based rSO 2 measurements yielded stable tissue rSO 2 -values of 76-78%, i.e. values expected also in other adequately perfused and oxygenated (muscle-) tissues., Conclusion: Despite the alarming, clinical finding of a grotesquely swollen, rubber-hard tongue and clinical concerns on the adequacy of the tongue perfusion and oxygenation, our measurements of both arterial pulsatility (SpO 2 ) and NIRS-based tissue oxygenation (rSO 2 ) suggested adequate perfusion and oxygenation of the tongue, rendering non-vitality of the tongue, e.g. by lingual venous thrombosis, unlikely. To our knowledge, this is the first clinical report of lingual rSO 2 measurement.

Postoperative Cognitive Dysfunction (POCD) is characterized by a deterioration in cognitive performance after surgery and is increasingly addressed in research studies. However, a uniform definition of POCD seems to be lacking, which is a major threat to clinical research in this area. We performed a focused systematic review to determine the current degree of heterogeneity in how POCD is defined across studies and to identify those diagnostic criteria that are used most commonly. The search identified 173 records, of which 30 were included. Neurocognitive testing was most commonly performed shortly before surgery and at 7 days postoperatively. A variety of neurocognitive tests were used to test a range of cognitive domains, including complex attention, language, executive functioning, perceptual-motor function, and learning and memory. The tests that were used most commonly were the Mini-Mental State Examination, the digit span test, the trail making test part A, and the digit symbol substitution test, but consensus on which test result would be considered "positive" for POCD was sparse. The results of this systematic review suggest the lack of a consistent approach towards defining POCD. However, commonalities were identified which may serve as a common denominator for deriving consensus-based diagnostic guidelines for POCD., Competing Interests: Kim van Sinderen, Lothar A. Schwarte, and Patrick Schober report no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Kim van Sinderen et al.)

Background: Prehospital management of severe traumatic brain injury (TBI) focuses on preventing secondary brain injury. Therefore, hypotension should be prevented, or if present, should be promptly treated in order to maintain optimal cerebral perfusion pressure. Fluid resuscitation is a traditional mainstay in the prehospital treatment of hypotension, however, the choice of fluid type that is to be administered in the prehospital setting is the subject of an on-going debate. This systematic review and meta-analysis was therefore performed to assess the effect of different fluid types on outcome in patients with severe TBI., Methods: PubMed, Embase and Web of Science were searched for articles up to March 2020. Studies comparing two or more prehospital administered fluid types with suspected or confirmed severe TBI were deemed eligible for inclusion. Studied outcomes were mortality and (extended) Glasgow Outcome Scale (GOS). The meta-analysis tested for differences in survival between hypertonic saline (HTS) and normotonic crystalloids (i.e. normal saline or Lactated Ringer's) and between hypertonic saline with dextran (HSD) and normotonic crystalloids. The systematic review is registered in the PROSPERO register with number CRD42020140423., Results: This literature search yielded a total of 519 articles, of which 12 were included in the systematic review and 6 were included in the meta-analysis. Eleven studies found no statistically significant difference in survival between patients treated with different fluid types (e.g. normal saline and hypertonic saline). All studies assessing neurological outcome, measured through (extended) GOS, found no statistically significant difference between different fluid types. Meta-analysis showed no better survival for patients treated with HSD, when compared to normotonic crystalloids (overall RR 0.99, 95% CI 0.93-1.06). Moreover, HTS compared to normotonic crystalloids does not result in a better survival (overall RR 1.04, 95% CI 0.97-1.12)., Conclusions: This systematic review and meta-analysis did not demonstrate a survival or neurological benefit for one specific fluid type administered in the prehospital setting., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Videolaryngoscopy is increasingly advocated as the standard intubation technique, while fibreoptic intubation is broadly regarded as the 'gold standard' for difficult airways. Traditionally, the training of these techniques is on patients, though manikins, simulators and cadavers are also used, with their respective limitations. In this study, we investigated whether the novel 'Fix for Life' (F4L) cadaver model is a suitable and realistic model for the teaching of these two intubation techniques to novices in airway management., Methods: Forty consultant anaesthetists and senior trainees were instructed to perform tracheal intubation with videolaryngoscopy and fibreoptic tracheoscopy in four F4L cadaver models. The primary outcome measure was the verbal rating scores (scale 1-10, higher scores indicate a better rating) for suitability and for realism of the F4L cadavers as training model for these techniques. Secondary outcomes included success rates of the procedures and the time to successful completion of the procedures., Results: The mean verbal rating scores for suitability and realism for videolaryngoscopy was 8.3 (95% CI, 7.9-8.6) and 7.2 (95% CI, 6.7-7.6), respectively. For fibreoptic tracheoscopy, suitability was 8.2 (95% CI, 7.9-8.5) and realism 7.5 (95% CI, 7.1-7.8). In videolaryngoscopy, 100% of the procedures were successful. The mean (SD) time until successful tracheal intubation was 34.8 (30.9) s. For fibreoptic tracheoscopy, the success rate was 96.3%, with a mean time of 89.4 (80.1) s., Conclusions: We conclude that the F4L cadaver model is a suitable and realistic model to train and teach tracheal intubation with videolaryngoscopy and fibreoptic tracheoscopy to novices in airway management training.

The primary aim of this systematic review is to describe the effects of prehospital transfusion of red blood cells (PHTRBC) on patient outcomes. Damage control resuscitation attempts to prevent death through haemorrhage in trauma patients. In this context, transfusion of red blood cells is increasingly used by emergency medical services (EMS). However, evidence on the effects on outcomes is scarce. PubMed and Web of Science were searched through January 2019; 55 articles were included. No randomised controlled studies were identified. While several observational studies suggest an increased survival after PHTRBC, consistent evidence for beneficial effects of PHTRBC on survival was not found. PHTRBC appears to improve haemodynamic parameters, but there is no evidence that shock on arrival to hospital is averted, nor of an association with trauma induced coagulopathy or with length of stay in hospitals or intensive care units. In conclusion, PHTRBC is increasingly used by EMS, but there is no strong evidence for effects of PHTRBC on mortality. Further research with study designs that allow causal inferences is required for more conclusive evidence. The combination of PHTRBC with plasma, as well as the use of individualised transfusion criteria, may potentially show more benefits and should be thoroughly investigated in the future. The review was registered at Prospero (CRD42018084658)., (© 2020 The Authors. Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)