To gel or not to gel - Tuning the sulfation pattern of carrageenans to expand their field of application.

Carrageenans represent a major cell wall component of red macro algae and, as established gelling and thickening agents, they contribute significantly to a broad variety of commercial applications in the food and cosmetic industry. As a highly sulfated class of linear polysaccharides, their functional properties are strongly related to the sulfation pattern of their carrabiose repeating units. Therefore, the biocatalytic fine-tuning of these polymers by generating tailored sulfation architectures harnessing the hydrolytic activity of sulfatases could be a powerful tool to produce novel polymer structures with tuned properties to expand applications of carrageenans beyond their current use. To contribute to this vision, we sought to identify novel carrageenan sulfatases by studying several putative carrageenolytic clusters in marine heterotrophic bacteria. This approach revealed two novel formylglycine-dependent sulfatases from Cellulophaga algicola DSM 14237 and Cellulophaga baltica DSM 24729 with promiscuous hydrolytic activity towards the sulfated galactose in the industrially established ι- and κ-carrageenan, converting them into α- and ß-carrageenan, respectively, and enabling the production of a variety of novel pure and hybrid carrageenans. The rheological analysis of these enzymatically generated structures revealed significantly altered physicochemical properties that may open the gate to a variety of novel carrageenan-based applications.

Emergency front-of-neck access in pediatric anesthesia: A narrative review.

BACKGROUND AND OBJECTIVES: Children undergoing airway management during general anesthesia may experience airway complications resulting in a rare but life-threatening situation known as "Can't Intubate, Can't Oxygenate". This situation requires immediate recognition, advanced airway management, and ultimately emergency front-of-neck access. The absence of standardized procedures, lack of readily available equipment, inadequate knowledge, and training often lead to failed emergency front-of-neck access, resulting in catastrophic outcomes. In this narrative review, we examined the latest evidence on emergency front-of-neck access in children. METHODS: A comprehensive literature was performed the use of emergency front-of-neck access (eFONA) in infants and children. RESULTS: Eighty-six papers were deemed relevant by abstract. Finally, eight studies regarding the eFONA technique and simulations in animal models were included. For all articles, their primary and secondary outcomes, their specific animal model, the experimental design, the target participants, and the equipment were reported. CONCLUSION: Based on the available evidence, we propose a general approach to the eFONA technique and a guide for implementing local protocols and training. Additionally, we introduce the application of innovative tools such as 3D models, ultrasound, and artificial intelligence, which can improve the precision, safety, and training of this rare but critical procedure.

Biocatalytic Conversion of Carrageenans for the Production of 3,6-Anhydro-D-galactose.

Marine biomass stands out as a sustainable resource for generating value-added chemicals. In particular, anhydrosugars derived from carrageenans exhibit a variety of biological functions, rendering them highly promising for utilization and cascading in food, cosmetic, and biotechnological applications. However, the limitation of available sulfatases to break down the complex sulfation patterns of carrageenans poses a significant limitation for the sustainable production of valuable bioproducts from red algae. In this study, we screened several carrageenolytic polysaccharide utilization loci for novel sulfatase activities to assist the efficient conversion of a variety of sulfated galactans into the target product 3,6-anhydro-D-galactose. Inspired by the carrageenolytic pathways in marine heterotrophic bacteria, we systematically combined these novel sulfatases with other carrageenolytic enzymes, facilitating the development of the first enzymatic one-pot biotransformation of ι- and κ-carrageenan to 3,6-anhdyro-D-galactose. We further showed the applicability of this enzymatic bioconversion to a broad series of hybrid carrageenans, rendering this process a promising and sustainable approach for the production of value-added biomolecules from red-algal feedstocks.

Emergency front-of-neck access in infants: A pragmatic crossover randomized control trial comparing two approaches on a simulated rabbit model.

BACKGROUND: Rapid-sequence tracheotomy and scalpel-bougie tracheotomy are two published approaches for establishing emergency front-of-neck access in infants. It is unknown whether there is a difference in performance times and success rates between the two approaches. AIMS: The aim of this cross-over randomized control trial study was to investigate whether the two approaches were equivalent for establishing tracheal access in rabbit cadavers. The underlying hypothesis was that the time to achieve the tracheal access is the same with both techniques. METHODS: Between May and September 2022, thirty physicians (pediatric anesthesiologists and intensivists) were randomized to perform front-of-neck access using one and then the other technique: rapid-sequence tracheotomy and scalpel-bougie tracheotomy. After watching training videos, each technique was practiced four times followed by a final tracheotomy during which study measurements were obtained. Based on existing data, an equivalence margin was set at ∆ = ±10 s for the duration of the procedure. The primary outcome was defined as the duration until tracheal tube placement was achieved successfully. Secondary outcomes included success rate, structural injuries, and subjective participant self-evaluation. RESULTS: The median duration of the scalpel-bougie tracheotomy was 48 s (95% CI: 37-57), while the duration of the rapid-sequence tracheotomy was 59 s (95% CI: 49-66, p = .07). The difference in the median duration between the two approaches was 11 s (95% CI: -4.9 to 29). The overall success rate was 93.3% (95% CI: 83.8%-98.2%). The scalpel-bougie tracheotomy resulted in significantly fewer damaged tracheal rings and was preferred among participants. CONCLUSIONS: The scalpel-bougie tracheotomy was slightly faster than the rapid-sequence tracheotomy and favored by participants, with fewer tracheal injuries. Therefore, we propose the scalpel-bougie tracheostomy as a rescue approach favoring the similarity to the adult approach for small children. The use of a comparable equipment kit for both children and adults facilitates standardization, performance, and logistics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05499273.

Airway management in neonates and infants: European Society of Anaesthesiology and Intensive Care and British Journal of Anaesthesia joint guidelines.

Airway management is required during general anaesthesia and is essential for life-threatening conditions such as cardiopulmonary resuscitation. Evidence from recent trials indicates a high incidence of critical events during airway management, especially in neonates or infants. It is important to define the optimal techniques and strategies for airway management in these groups. In this joint European Society of Anaesthesiology and Intensive Care (ESAIC) and British Journal of Anaesthesia (BJA) guideline on airway management in neonates and infants, we present aggregated and evidence-based recommendations to assist clinicians in providing safe and effective medical care. We identified seven main areas of interest for airway management: i) preoperative assessment and preparation; ii) medications; iii) techniques and algorithms; iv) identification and treatment of difficult airways; v) confirmation of tracheal intubation; vi) tracheal extubation, and vii) human factors. Based on these areas, Population, Intervention, Comparison, Outcomes (PICO) questions were derived that guided a structured literature search. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to formulate the recommendations based on those studies included with consideration of their methodological quality (strong '1' or weak '2' recommendation with high 'A', medium 'B' or low 'C' quality of evidence). In summary, we recommend: 1. Use medical history and physical examination to predict difficult airway management (1C). 2. Ensure adequate level of sedation or general anaesthesia during airway management (1B). 3. Administer neuromuscular blocker before tracheal intubation when spontaneous breathing is not necessary (1C). 4. Use a videolaryngoscope with an age-adapted standard blade as first choice for tracheal intubation (1B). 5. Apply apnoeic oxygenation during tracheal intubation in neonates (1B). 6. Consider a supraglottic airway for rescue oxygenation and ventilation when tracheal intubation fails (1B). 7. Limit the number of tracheal intubation attempts (1C). 8. Use a stylet to reinforce and preshape tracheal tubes when hyperangulated videolaryngoscope blades are used and when the larynx is anatomically anterior (1C). 9. Verify intubation is successful with clinical assessment and end-tidal CO2 waveform (1C). 10. Apply high-flow nasal oxygenation, continuous positive airway pressure or nasal intermittent positive pressure ventilation for postextubation respiratory support, when appropriate (1B).

Apnoeic oxygenation during paediatric tracheal intubation: a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen administration by apnoeic oxygenation during laryngoscopy for tracheal intubation is intended to prolong safe apnoea time, reduce the risk of hypoxaemia, and increase the success rate of first-attempt tracheal intubation under general anaesthesia. This systematic review examined the efficacy and effectiveness of apnoeic oxygenation during tracheal intubation in children. METHODS: This systematic review and meta-analysis included randomised controlled trials and non-randomised studies in paediatric patients requiring tracheal intubation, evaluating apnoeic oxygenation by any method compared with patients without apnoeic oxygenation. Searched databases were MEDLINE, Embase, Cochrane Library, CINAHL, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), Scopus, and Web of Science from inception to March 22, 2023. Data extraction and risk of bias assessment followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) recommendation. RESULTS: After initial selection of 40 708 articles, 15 studies summarising 9802 children were included (10 randomised controlled trials, four pre-post studies, one prospective observational study) published between 1988 and 2023. Eight randomised controlled trials were included for meta-analysis (n=1070 children; 803 from operating theatres, 267 from neonatal intensive care units). Apnoeic oxygenation increased intubation first-pass success with no physiological instability (risk ratio [RR] 1.27, 95% confidence interval [CI] 1.03-1.57, P=0.04, I2=0), higher oxygen saturation during intubation (mean difference 3.6%, 95% CI 0.8-6.5%, P=0.02, I2=63%), and decreased incidence of hypoxaemia (RR 0.24, 95% CI 0.17-0.33, P<0.01, I2=51%) compared with no supplementary oxygen administration. CONCLUSION: This systematic review with meta-analysis confirms that apnoeic oxygenation during tracheal intubation of children significantly increases first-pass intubation success rate. Furthermore, apnoeic oxygenation enables stable physiological conditions by maintaining oxygen saturation within the normal range. CLINICAL TRIAL REGISTRATION: Protocol registered prospectively on PROSPERO (registration number: CRD42022369000) on December 2, 2022.

Airway management in neonates and infants: European Society of Anaesthesiology and Intensive Care and British Journal of Anaesthesia joint guidelines.

Airway management is required during general anaesthesia and is essential for life-threatening conditions such as cardiopulmonary resuscitation. Evidence from recent trials indicates a high incidence of critical events during airway management, especially in neonates or infants. It is important to define the optimal techniques and strategies for airway management in these groups. In this joint European Society of Anaesthesiology and Intensive Care (ESAIC) and British Journal of Anaesthesia (BJA) guideline on airway management in neonates and infants, we present aggregated and evidence-based recommendations to assist clinicians in providing safe and effective medical care. We identified seven main areas of interest for airway management: i) preoperative assessment and preparation; ii) medications; iii) techniques and algorithms; iv) identification and treatment of difficult airways; v) confirmation of tracheal intubation; vi) tracheal extubation, and vii) human factors. Based on these areas, Population, Intervention, Comparison, Outcomes (PICO) questions were derived that guided a structured literature search. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to formulate the recommendations based on those studies included with consideration of their methodological quality (strong '1' or weak '2' recommendation with high 'A', medium 'B' or low 'C' quality of evidence). In summary, we recommend: 1. Use medical history and physical examination to predict difficult airway management (1С). 2. Ensure adequate level of sedation or general anaesthesia during airway management (1B). 3. Administer neuromuscular blocker before tracheal intubation when spontaneous breathing is not necessary (1С). 4. Use a videolaryngoscope with an age-adapted standard blade as first choice for tracheal intubation (1B). 5. Apply apnoeic oxygenation during tracheal intubation in neonates (1B). 6. Consider a supraglottic airway for rescue oxygenation and ventilation when tracheal intubation fails (1B). 7. Limit the number of tracheal intubation attempts (1C). 8. Use a stylet to reinforce and preshape tracheal tubes when hyperangulated videolaryngoscope blades are used and when the larynx is anatomically anterior (1C). 9. Verify intubation is successful with clinical assessment and end-tidal CO 2 waveform (1C). 10. Apply high-flow nasal oxygenation, continuous positive airway pressure or nasal intermittent positive pressure ventilation for postextubation respiratory support, when appropriate (1B).

A Retrospective before and after Assessment of Multidisciplinary Management for Postpartum Hemorrhage.

Postpartum hemorrhage (PPH) remains a major cause of maternal morbidity and mortality. While PPH treatment guidelines exist, data on their effect on reduction in red blood cell (RBC) transfusions and use of hemostatic products are scarce. Continuous evaluation of PPH management is important to assess potential pitfalls and incorporate new treatment options. We retrospectively compared PPH management and administration of RBC and hemostatic products before and after international guideline implementation. The primary endpoint was RBC administration for PPH. Secondary endpoints were hemoglobin trigger for RBC administration, administration of hemostatic products and surgical therapies. In total 235 patients had a PPH, 59 in 2011 and 176 in 2018. In 2018, fewer patients received RBC within 24 h (2018: 10% vs. 2011: 32%, p < 0.001) and 24 h after delivery (2018: 4.5% vs. 2011: 37%, p < 0.001). The number of RBC units transfused per case was significantly lower in 2018 (two vs. four units in 2011, p = 0.013). A significantly reduced transfusion of fresh frozen plasma and platelets was observed in 2018 (p < 0.001 and p = 0.002, respectively). In 2011, additional surgeries for PPH in both the acute and subacute phase were performed more frequently. Local implementation of multidisciplinary PPH guidelines is feasible and was associated with a significant reduction in transfused blood products.

Favourable neurological outcome following paediatric out-of-hospital cardiac arrest: a retrospective observational study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) in children is rare and can potentially result in severe neurological impairment. Our study aimed to identify characteristics of and factors associated with favourable neurological outcome following the resuscitation of children by the Swiss helicopter emergency medical service. MATERIALS AND METHODS: This retrospective observational study screened the Swiss Air-Ambulance electronic database from 01-01-2011 to 31-12-2021. We included all primary missions for patients ≤ 16 years with OHCA. The primary outcome was favourable neurological outcome after 30 days (cerebral performance categories (CPC) 1 and 2). Multivariable linear regression identified potential factors associated with favourable outcome (odd ratio - OR). RESULTS: Having screened 110,331 missions, we identified 296 children with OHCA, which we included in the analysis. Patients were 5.0 [1.0; 12.0] years old and 61.5% (n = 182) male. More than two-thirds had a non-traumatic OHCA (67.2%, n = 199), while 32.8% (n = 97) had a traumatic OHCA. Thirty days after the event, 24.0% (n = 71) of patients were alive, 18.9% (n = 56) with a favourable neurological outcome (CPC 1 n = 46, CPC 2 n = 10). Bystander cardiopulmonary resuscitation (OR 10.34; 95%CI 2.29-51.42; p = 0.002) and non-traumatic aetiology (OR 11.07 2.38-51.42; p = 0.002) were the factors most strongly associated with favourable outcome. Factors associated with an unfavourable neurological outcome were initial asystole (OR 0.12; 95%CI 0.04-0.39; p < 0.001), administration of adrenaline (OR 0.14; 95%CI 0.05-0.39; p < 0.001) and ongoing chest compression at HEMS arrival (OR 0.17; 95%CI 0.04-0.65; p = 0.010). CONCLUSION: In this study, 18.9% of paediatric OHCA patients survived with a favourable neurologic outcome 30 days after treatment by the Swiss helicopter emergency medical service. Immediate bystander cardiopulmonary resuscitation and non-traumatic OHCA aetiology were the factors most strongly associated with a favourable neurological outcome. These results underline the importance of effective bystander and first-responder rescue as the foundation for subsequent professional treatment of children in cardiac arrest.

Assessment of Rheological Models Applied to Blood Flow in Human Thoracic Aorta.

PURPOSE: The purpose of this study is to assess the importance of non-Newtonian rheological models on blood flow in the human thoracic aorta. METHODS: The pulsatile flow in the aorta is simulated using the models of Casson, Quemada and Walburn-Schneck in addition to a case of fixed (Newtonian) viscosity. The impact of the four rheological models (using constant hematocrit) was assessed with respect to (i) magnitude and deviation of the viscosity relative to a reference value (the Newtonian case); (ii) wall shear stress (WSS) and its time derivative; (iii) common WSS-related indicators, OSI, TAWSS and RRT; (iv) relative volume and surface-based retrograde flow; and (v) the impact of rheological models on the transport of small particles in the thoracic aorta. RESULTS: The time-dependent flow in the thoracic aorta implies relatively large variations in the instantaneous WSS, due to variations in the instantaneous viscosity by as much as an order of magnitude. The largest effect was observed for low shear rates (tens s-1). The different viscosity models had a small impact in terms of time- and spaced-averaged quantities. The significance of the rheological models was clearly demonstrated in the instantaneous WSS, for the space-averaged WSS (about 10%) and the corresponding temporal derivative of WSS (up to 20%). The longer-term accumulated effect of the rheological model was observed for the transport of spherical particles of 2 mm and 2 mm in diameter (density of 1200 kg/m3). Large particles' total residence time in the brachiocephalic artery was 60% longer compared to the smaller particles. For the left common carotid artery, the opposite was observed: the smaller particles resided considerably longer than their larger counterparts. CONCLUSIONS: The dependence on the non-Newtonian properties of blood is mostly important at low shear regions (near walls, stagnation regions). Time- and space-averaging parameters of interest reduce the impact of the rheological model and may thereby lead to under-estimation of viscous effects. The rheological model affects the local WSS and its temporal derivative. In addition, the transport of small particles includes the accumulated effect of the blood rheological model as the several forces (e.g., drag, added mass and lift) acting on the particles are viscosity dependent. Mass transport is an essential factor for the development of pathologies in the arterial wall, implying that rheological models are important for assessing such risks.

ChatGPT's performance in dentistry and allergy-immunology assessments: a comparative study.

Large language models (LLMs) such as ChatGPT have potential applications in healthcare, including dentistry. Priming, the practice of providing LLMs with initial, relevant information, is an approach to improve their output quality. This study aimed to evaluate the performance of ChatGPT 3 and ChatGPT 4 on self-assessment questions for dentistry, through the Swiss Federal Licensing Examination in Dental Medicine (SFLEDM), and allergy and clinical immunology, through the European Examination in Allergy and Clinical Immunology (EEAACI). The second objective was to assess the impact of priming on ChatGPT's performance. The SFLEDM and EEAACI multiple-choice questions from the University of Bern's Institute for Medical Education platform were administered to both ChatGPT versions, with and without priming. Performance was analyzed based on correct responses. The statistical analysis included Wilcoxon rank sum tests (α=0.05). The average accuracy rates in the SFLEDM and EEAACI assessments were 63.3% and 79.3%, respectively. Both ChatGPT versions performed better on EEAACI than SFLEDM, with ChatGPT 4 outperforming ChatGPT 3 across all tests. ChatGPT 3's performance exhibited a significant improvement with priming for both EEAACI (p=0.017) and SFLEDM (p=0.024) assessments. For ChatGPT 4, the priming effect was significant only in the SFLEDM assessment (p=0.038). The performance disparity between SFLEDM and EEAACI assessments underscores ChatGPT's varying proficiency across different medical domains, likely tied to the nature and amount of training data available in each field. Priming can be a tool for enhancing output, especially in earlier LLMs. Advancements from ChatGPT 3 to 4 highlight the rapid developments in LLM technology. Yet, their use in critical fields such as healthcare must remain cautious owing to LLMs' inherent limitations and risks.

Atelectasis in obese patients undergoing laparoscopic bariatric surgery are not increased upon discharge from Post Anesthesia Care Unit.

Background: Obese patients frequently develop pulmonary atelectasis upon general anesthesia. The risk is increased during laparoscopic surgery. This prospective, observational single-center study evaluated atelectasis dynamics using Electric Impedance Tomography (EIT) in patients undergoing laparoscopic bariatric surgery. Methods: We included adult patients with ASA physical status I-IV and a BMI of ≥40. Exclusion criteria were known severe pulmonary hypertension, home oxygen therapy, heart failure, and recent pulmonary infections. The primary outcome was the proportion of poorly ventilated lung regions (low tidal variation areas) and the global inhomogeneity (GI) index assessed by EIT before discharge from the Post Anesthesia Care Unit compared to these same measures prior to initiation of anesthesia. Results: The median (IQR) proportion of low tidal variation areas at the different analysis points were T1 10.8% [3.6-15.1%] and T5 10.3% [2.6-18.9%], and the mean difference was -0.7% (95% CI: -5.8% -4.5%), i.e., lower than the predefined non-inferiority margin of 5% (p = 0.022). There were no changes at the four additional time points compared to T1 or postoperative pulmonary complications during the 14 days following the procedure. Conclusion: We found that obese patients undergoing laparoscopic bariatric surgery do not leave the Post Anesthesia Care Unit with increased low tidal variation areas compared to the preoperative period.

Medical device education: study protocol for a randomised controlled trial comparing self-directed learning with traditional instructor-led learning on an anaesthesia workstation.

INTRODUCTION: Continuous professional development is essential for maintaining competencies in healthcare. This applies to medical device knowledge and safe handling, which are fundamental for patient safety. Little is known about the efficiency of self-directed learning with an integrated video in medical device education. This study investigates whether anaesthesia providers acquire their medical device competencies on an anaesthesia workstation differently via self-directed learning than traditional teacher-led workshops. METHODS AND ANALYSIS: This single-centre, non-inferiority, randomised, controlled trial aims to enrol at least 224 anaesthesia providers (ie, certified nurses and physicians). Participants will be randomised to (1) self-directed learning with an integrated learning video (intervention) or (2) a traditional teacher-led workshop (control), for a 1-hour session on a new anaesthesia workstation. The two educational approaches and their effect on medical device competence will be assessed concerning 12 competencies in the same 10 min, objective, structured, clinical examination-like station for both groups. The primary endpoint will be an assessment score of ≥60%. Non-inferiority will be declared if the upper limit of a 90% two-sided CI excludes a difference of more than 10% in favour of the control group. Secondary endpoints will be: (1) the score achieved in the study assessment, (2) the number of open questions after the training, (3) training time in minutes, (4) use of resources and (5) costs, all of which are compared between both groups. ETHICS AND DISSEMINATION: Study participants will provide written informed consent. All recorded data will be stored on a password-protected research server at the study site accessible only to the investigators. The Bern Cantonal Ethics Committee waived the need for ethical approval (Req-2021-00837; 25 July 2021). There are no ethical, legal or security issues regarding data collection, processing, storage or dissemination. TRIAL REGISTRATION NUMBER: NCT05530382, 7 September 2022; ClinicalTrials.gov.

Characteristics and neurological survival following intraoperative cardiac arrest in a Swiss University Hospital: a 7-year retrospective observational cohort study.

Introduction: Little is known about intraoperative cardiac arrest during anesthesia care. In particular, data on characteristics of cardiac arrest and neurological survival are scarce. Methods: We conducted a single-center retrospective observational study evaluating anesthetic procedures from January 2015 until December 2021. We included patients with an intraoperative cardiac arrest and excluded cardiac arrest outside of the operating room. The primary outcome was the return of spontaneous circulation (ROSC). Secondary outcomes were sustained ROSC over 20 min, 30-day survival, and favorable neurological outcome according to Clinical Performance Category (CPC) 1 and 2. Results: We screened 228,712 anesthetic procedures, 195 of which met inclusion criteria and were analyzed. The incidence of intraoperative cardiac arrest was 90 (CI 95% 78-103) in 100,000 procedures. The median age was 70.5 [60.0; 79.4] years, and two-thirds of patients (n = 135; 69.2%) were male. Most of these patients with cardiac arrest had ASA physical status IV (n = 83; 42.6%) or V (n = 47; 24.1%). Cardiac arrest occurred more frequently (n = 104; 53.1%) during emergency procedures than elective ones (n = 92; 46.9%). Initial rhythm was pre-dominantly non-shockable with pulseless electrical activity mostly. Most patients (n = 163/195, 83.6%; CI 95 77.6-88.5%) had at least one instance of ROSC. Sustained ROSC over 20 min was achieved in most patients with ROSC (n = 147/163; 90.2%). Of the 163 patients with ROSC, 111 (68.1%, CI 95 60.4-75.2%) remained alive after 30 days, and most (n = 90/111; 84.9%) had favorable neurological survival (CPC 1 and 2). Conclusion: Intraoperative cardiac arrest is rare but is more likely in older patients, patients with ASA physical status ≥IV, cardiac and vascular surgery, and emergency procedures. Patients often present with pulseless electrical activity as the initial rhythm. ROSC can be achieved in most patients. Over half of the patients are alive after 30 days, most with favorable neurological outcomes, if treated immediately.

Factors influencing on-scene time in a physician-staffed helicopter emergency medical service (HEMS): a retrospective observational study.

BACKGROUND: For helicopter emergency service systems (HEMS), the prehospital time consists of response time, on-scene time and transport time. Little is known about the factors that influence on-scene time or about differences between adult and paediatric missions in a physician-staffed HEMS. METHODS: We analysed the HEMS electronic database of Swiss Air-Rescue from 01-01-2011 to 31-12-2021 (N = 110,331). We included primary missions and excluded missions with National Advisory Committee for Aeronautics score (NACA) score 0 or 7, resulting in 68,333 missions for analysis. The primary endpoint 'on-scene time' was defined as first physical contact with the patient until take-off to the hospital. A multivariable linear regression model was computed to examine the association of diagnosis, type and number of interventions and monitoring, and patient's characteristics with the primary endpoint. RESULTS: The prehospital time and on-scene time of the missions studied were, respectively, 50.6 [IQR: 41.0-62.0] minutes and 21.0 [IQR: 15.0-28.6] minutes. Helicopter hoist operations, resuscitation, airway management, critical interventions, remote location, night-time, and paediatric patients were associated with longer on-scene times. CONCLUSIONS: Compared to adult patients, the adjusted on-scene time for paediatric patients was longer. Besides the strong impact of a helicopter hoist operation on on-scene time, the dominant factors contributing to on-scene time are the type and number of interventions and monitoring: improving individual interventions or performing them in parallel may offer great potential for reducing on-scene time. However, multiple clinical interventions and monitoring interact and are not single interventions. Compared to the impact of interventions, non-modifiable factors, such as NACA score, type of diagnosis and age, make only a minor contribution to overall on-scene time.

Release of Hyaluronan in Aneurysmal Subarachnoid Hemorrhage and Cerebral Vasospasm: A Pilot Study Indicating a Shedding of the Endothelial Glycocalyx.

BACKGROUND: This pilot study investigated plasma concentrations of hyaluronan, heparan sulfate, and syndecan-1 as possible biomarkers for glycocalyx integrity after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Daily blood samples for biomarker assay were obtained in aSAH patients on the intensive care unit stay and compared with samples from a historic cohort of 40 healthy controls. In post hoc subgroup analyses in patients with and without cerebral vasospasm, we explored the influence of aSAH-related cerebral vasospasm on biomarker levels. RESULTS: A total of 18 aSAH patients and 40 historic controls were included in the study. Median (interquartile range) plasma levels of hyaluronan were higher in aSAH patients compared with controls (131 [84 to 179] vs. 92 [82 to 98] ng/mL, respectively; P=0.009), whereas heparan sulfate (mean±SD: 754±428 vs. 1329±316 ng/mL; P<0.001) and syndecan-1 (median: 23 [17 to 36] vs. 30 [23 to 52] ng/mL; P=0.02) levels were lower. Patients who developed vasospasm had significantly higher median hyaluronan concentrations at day 7 (206 [165 to 288] vs. 133 [108 to 164] ng/mL, respectively; P=0.009) and at day of first vasospasm detection (203 [155 to 231] vs. 133 [108 to 164] ng/mL, respectively; P=0.01) compared with those without vasospasm. Heparan sulfate and syndecan-1 concentrations were similar in patients with and without vasospasm. CONCLUSIONS: The increased plasma concentrations of hyaluronan after aSAH suggest selective shedding of this component of the glycocalyx. Increased levels of hyaluronan in patients with cerebral vasospasm, underlines a potential role for hyaluronan in vasospasm processes.

Microvascular perfusion, perfused boundary region and glycocalyx shedding in patients with autosomal dominant polycystic kidney disease: results from the GlycoScore III study.

Background: Vascular abnormalities and endothelial dysfunction are part of the spectrum of autosomal dominant polycystic kidney disease (ADPKD). The mechanisms behind these manifestations, including potential effects on the endothelial surface layer (ESL) and glycocalyx integrity, remain unknown. Methods: Forty-five ambulatory adult patients with ADPKD were enrolled in this prospective, observational, cross-sectional, single-centre study. Fifty-one healthy volunteers served as a control group. All participants underwent real-time microvascular perfusion measurements of the sublingual microcirculation using sidestream dark field imaging. After image acquisition, the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration into the ESL, was automatically calculated. Microvascular perfusion was assessed by RBC filling and capillary density. Concentrations of circulating glycocalyx components were determined by enzyme-linked immunosorbent assay. Results: ADPKD patients showed a significantly larger PBR compared with healthy controls (2.09 ± 0.23 µm versus 1.79 ± 0.25 µm; P < .001). This was accompanied by significantly lower RBC filling (70.4 ± 5.0% versus 77.9 ± 5.4%; P < .001) as well as a higher valid capillary density {318/mm2 [interquartile range (IQR) 269-380] versus 273/mm2 [230-327]; P = .007}. Significantly higher plasma concentrations of heparan sulphate (1625 ± 807 ng/ml versus 1329 ± 316 ng/ml; P = .034), hyaluronan (111 ng/ml [IQR 79-132] versus 92 ng/ml [82-98]; P = .042) and syndecan-1 were noted in ADPKD patients compared with healthy controls (35 ng/ml [IQR 27-57] versus 29 ng/ml [23-42]; P = .035). Conclusions: Dimensions and integrity of the ESL are impaired in ADPKD patients. Increased capillary density may be a compensatory mechanism for vascular dysfunction to ensure sufficient tissue perfusion and oxygenation.

Direct versus video laryngoscopy with standard blades for neonatal and infant tracheal intubation with supplemental oxygen: a multicentre, non-inferiority, randomised controlled trial.

BACKGROUND: Tracheal intubation in neonates and infants is a potentially life-saving procedure. Video laryngoscopy has been found to improve first-attempt tracheal intubation success and reduce complications compared with direct laryngoscopy in children younger than 12 months. Supplemental periprocedural oxygen might increase the likelihood of successful first-attempt intubation because of an increase in safe apnoea time. We tested the hypothesis that direct laryngoscopy is not inferior to video laryngoscopy when using standard blades and supplemental oxygen is provided. METHODS: We did a non-inferiority, international, multicentre, single-blinded, randomised controlled trial, in which we randomly assigned neonates and infants aged up to 52 weeks postmenstrual age scheduled for elective tracheal intubation to either direct laryngoscopy or video laryngoscopy (1:1 ratio, randomly assigned using a secure online service) at seven tertiary paediatric hospitals across Australia, Canada, Italy, Switzerland, and the USA. An expected difficult intubation was the main exclusion criteria. Parents and patients were masked to the assigned group of treatment. All infants received supplemental oxygen (1 L/Kg per min) during laryngoscopy until the correct tracheal tube position was confirmed. The primary outcome was the proportion of first-attempt tracheal intubation success, defined as appearance of end-tidal CO2 curve at the anaesthesia monitor, between the two groups in the modified intention-to-treat analysis. A 10% non-inferiority margin between direct laryngoscopy or video laryngoscopy was applied. The trial is registered with ClinicalTrials.gov (NCT04295902) and is now concluded. FINDINGS: Of 599 patients assessed, 250 patients were included between Oct 26, 2020, and March 11, 2022. 244 patients were included in the final modified intention-to-treat analysis. The median postmenstrual age on the day of intubation was 44·0 weeks (IQR 41·0-48·0) in the direct laryngoscopy group and 46·0 weeks (42·0-49·0) in the video laryngoscopy group, 34 (28%) were female in the direct laryngoscopy group and 38 (31%) were female in the video laryngoscopy group. First-attempt tracheal intubation success rate with no desaturation was higher with video laryngoscopy (89·3% [95% CI 83·7 to 94·8]; n=108/121) compared with direct laryngoscopy (78·9% [71·6 to 86·1]; n=97/123), with an adjusted absolute risk difference of 9·5% (0·8 to 18·1; p=0·033). The incidence of adverse events between the two groups was similar (-2·5% [95% CI -9·6 to 4·6]; p=0·490). Post-anaesthesia complications occurred seven times in six patients with no difference between the groups. INTERPRETATION: Video laryngoscopy with standard blades in combination with supplemental oxygen in neonates and infants might increase the success rate of first-attempt tracheal intubation, when compared with direct laryngoscopy with supplemental oxygen. The incidence of hypoxaemia increased with the number of attempts, but was similar between video laryngoscopy and direct laryngoscopy. Video laryngoscopy with oxygen should be considered as the technique of choice when neonates and infants are intubated. FUNDING: Swiss Pediatric Anaesthesia Society, Swiss Society for Anaesthesia and Perioperative Medicine, Foundation for Research in Anaesthesiology and Intensive Care Medicine, Channel 7 Telethon Trust, Stan Perron Charitable Foundation, National Health and Medical Research Council.

ChatGPT's performance in dentistry and allergyimmunology assessments: a comparative study.

Large language models (LLMs) such as ChatGPT have potential applications in healthcare, including dentistry. Priming, the practice of providing LLMs with initial, relevant information, is an approach to improve their output quality. This study aimed to evaluate the performance of ChatGPT 3 and ChatGPT 4 on self-assessment questions for dentistry, through the Swiss Federal Licensing Examination in Dental Medicine (SFLEDM), and allergy and clinical immunology, through the European Examination in Allergy and Clinical Immunology (EEAACI). The second objective was to assess the impact of priming on ChatGPT's performance. The SFLEDM and EEAACI multiple-choice questions from the University of Bern's Institute for Medical Education platform were administered to both ChatGPT versions, with and without priming. Performance was analyzed based on correct responses. The statistical analysis included Wilcoxon rank sum tests (alpha=0.05). The average accuracy rates in the SFLEDM and EEAACI assessments were 63.3% and 79.3%, respectively. Both ChatGPT versions performed better on EEAACI than SFLEDM, with ChatGPT 4 outperforming ChatGPT 3 across all tests. ChatGPT 3's performance exhibited a significant improvement with priming for both EEAACI (p=0.017) and SFLEDM (p=0.024) assessments. For ChatGPT 4, the priming effect was significant only in the SFLEDM assessment (p=0.038). The performance disparity between SFLEDM and EEAACI assessments underscores ChatGPT's varying proficiency across different medical domains, likely tied to the nature and amount of training data available in each field. Priming can be a tool for enhancing output, especially in earlier LLMs. Advancements from ChatGPT 3 to 4 highlight the rapid developments in LLM technology. Yet, their use in critical fields such as healthcare must remain cautious owing to LLMs' inherent limitations and risks.