Effects of temporal IFNγ exposure on macrophage phenotype and secretory profile: exploring GMP-Compliant production of a novel subtype of regulatory macrophages (MregIFNγ0) for potential cell therapeutic applications.

BACKGROUND: Macrophages are involved in tissue homeostasis, angiogenesis and immunomodulation. Proangiogenic and anti-inflammatory macrophages (regulatory macrophages, Mreg) can be differentiated in-vitro from CD14+ monocytes by using a defined cell culture medium and a stimulus of IFNγ. AIM OF THE STUDY: To scrutinize the potential impact of temporal IFNγ exposure on macrophage differentiation as such exposure may lead to the emergence of a distinct and novel macrophage subtype. METHODS: Differentiation of human CD14+ monocytes to Mreg was performed using a GMP compliant protocol and administration of IFNγ on day 6. Monocytes from the same donor were in parallel differentiated to MregIFNγ0 using the identical protocol but with administration of IFNγ on day 0. Cell characterization was performed using brightfield microscopy, automated and metabolic cell analysis, transmission electron microscopy, flow cytometry, qPCR and secretome profiling. RESULTS: Mreg and MregIFNγ0 showed no differences in cell size and volume. However, phenotypically MregIFNγ0 exhibited fewer intracellular vesicles/vacuoles but larger pseudopodia-like extensions. MregIFNγ0 revealed reduced expression of IDO and PD-L1 (P < 0.01 for both). They were positive for CD80, CD14, CD16 and CD38 (P < 0.0001vs. Mreg for all), while the majority of MregIFNγ0 did not express CD206, CD56, and CD103 on their cell surface (P < 0.01 vs. Mreg for all). In terms of their secretomes, MregIFNγ0 differed significantly from Mreg. MregIFNγ0 media exhibited reduced levels of ENA-78, Osteopontin and Serpin E1, while the amounts of MIG (CXCL9) and IP10 were increased. CONCLUSION: Exposing CD14+ monocytes to an alternatively timed IFNγ stimulation results in a novel macrophage subtype which possess additional M1-like features (MregIFNγ0). MregIFNγ0 may therefore have the potential to serve as cellular therapeutics for clinical applications beyond those covered by M2-like Mreg, including immunomodulation and tumor treatment.

Optimal Chest Compression Point During Pediatric Resuscitation: Implications for Pediatric Resuscitation Practice by CT Scans.

OBJECTIVES: Current European guidelines for pediatric cardiopulmonary resuscitation (CPR) recommend the lower half of the sternum as the chest compression point (CP). In this study, we have used thoracic CT scans to evaluate recommended and optimal CP in relation to cardiac anatomy and structure. DESIGN: Analysis of routinely acquired thoracic CT scans acquired from 2000 to 2020. SETTING: Single-center pediatric department in a German University Hospital. PATIENTS: Imaging data were obtained from 290 patients of 3-16 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured and analyzed 14 thoracic metrics in each thoracic CT scan. In 44 of 290 (15.2%) scans, the recommended CP did not match the level of the cardiac ventricles. Anatomically, the optimal CP was one rib or one vertebral body lower than the recommended CP, that is, the optimal CP was more caudal to the level of the body of the sternum in 67 of 290 (23.1%) scans. The recommended compression depth appeared reasonable in children younger than 12 years old. At 12 years old or older, the maximum compression depth of 6 cm is less than or equal to one-third of the thoracic depth. CONCLUSIONS: In this study of thoracic CT scans in children 3-16 years old, we have found that optimal CP for CPR appears to be more caudal than the recommended CP. Therefore, it seems reasonable to prefer to use the lower part of the sternum for CPR chest compressions. At 12 years old or older, a compression depth similar to that used in adults-6 cm limit-may be chosen.

Liver transplantation for HCC in cirrhosis: Are Milan criteria outdated?

In Germany, organ allocation is based on the MELD-system and lab-MELD is usually low in patients with hepatocellular carcinoma (HCC) in cirrhosis. Higher medical urgency can be achieved by standard exception for HCC (SE-HCC), if Milan criteria (MC) are met. Noteworthy, UNOS T2 reflects MC, but excludes singular lesions < 2 cm. Thus, SE-HCC is awarded to patients with one lesion between 2 and 5 cm or 2 to 3 lesions between 1 and 3 cm. These criteria are static and do not reflect biological properties of HCC.We present a retrospective cohort of 111 patients, who underwent liver transplantation at UKSH, Campus Kiel between 2007 and 2017. No difference was found in overall survival for patient cohorts using Milan, UCSF, up-to-seven, and French-AFP criteria. However, there was a significantly reduced survival, if microvascular invasion was detected in the explanted organ and in patients with HCC-recurrence. The exclusive use of static selection criteria including MC appear to limit the access to liver transplantation.

Quality and safety in prehospital airway management - retrospective analysis of 18,000 cases from an air rescue database in Germany.

BACKGROUND: Prehospital airway management remains crucial with regard to the quality and safety of emergency medical service (EMS) systems worldwide. In 2007, the benchmark study by Timmermann et al. hit the German EMS community hard by revealing a significant rate of undetected oesophageal intubations leading to an often-fatal outcome. Since then, much attention has been given to guideline development and training. This study evaluated the incidence and special circumstances of tube misplacement as an adverse peri-intubation event from a Helicopter Emergency Medical Services perspective. METHODS: This was a retrospective analysis of a German helicopter-based EMS database from January 1, 2012, to December 31, 2020. All registered patients were included in the primary analysis. The results were analysed using SPSS 27.0.1.0. RESULTS: Out of 227,459 emergency medical responses overall, a total of 18,087 (8.0%) involved invasive airway management. In 8141 (45.0%) of these patients, airway management devices were used by ground-based EMS staff, with an intubation rate of 96.6% (n = 7861), and alternative airways were used in 3.2% (n = 285). Overall, the rate of endotracheal intubation success was 94.7%, while adverse events in the form of tube misplacement were present in 5.3%, with a 1.2% rate of undetected oesophageal intubation. Overall tube misplacement and undetected oesophageal intubation occurred more often after intubation was carried out by paramedics (10.4% and 3.6%, respectively). In view of special circumstances, those errors occurred more often in the presence of trauma or cardiopulmonary resuscitation, with rates of 5.6% and 6.4%, respectively. Difficult airways with a Cormack 4 status were present in 2.1% (n = 213) of HEMS patients, accompanied by three or more intubation attempts in 5.2% (n = 11). CONCLUSIONS: Prehospital airway management success has improved significantly in recent years. However, adverse peri-intubation events such as undetected oesophageal intubation remain a persistent threat to patient safety. TRIAL REGISTRATION: The study was registered in the German Register for Clinical Studies (number DRKS00028068).

Does the gender of emergency physicians have an impact on the prehospital care of psychiatric emergencies? a retrospective cohort analysis.

BACKGROUND: Psychiatric emergencies pose a special challenge for emergency physicians. It is known from other areas of medicine that the influence of a doctor's gender can have an impact on the type of treatment and quality of patient care. However, this has not yet been investigated in the context of prehospital care in psychiatric emergencies. OBJECTIVES: To identify whether the gender of the prehospital emergency physicians has an influence on the "on-scene" time, treatment strategy and on the potential escalation of interventions for patients with a psychiatric diagnosis. METHODS: A retrospective cohort analysis of emergency missions with a psychiatric diagnosis was performed between January 1, 2015 and December 31, 2021 at the Department of Emergency Medicine, Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Germany. RESULTS: 2882 emergency missions with a psychiatric indication/prehospital psychiatric diagnosis were studied and divided into: intoxication (n = 1343, 46.6%), suicidal behavior (n = 488, 16.9%), exceptional mental situation (n = 282, 9.8%), agitation (n = 262, 9.1%), anxiety and panic disorders (n = 262, 9.1%) and "psychiatric miscellaneous" (n = 245, 8.5%). Inpatient hospitalization occurred in 67.9% (n = 1958) of emergency missions. Of these, 20.3% (n = 392) were admitted directly to a psychiatric hospital. Male emergency physicians had a slightly longer "on-scene" time for psychiatric emergencies than female emergency physicians (p = 0.024). However, the variance in "on-scene" time for all interventions was significantly greater for female emergency physicians than for male emergency physicians (p = 0.025). Male emergency physicians were significantly more likely than their female counterparts to administer intravenous hypnotics in prehospital psychiatric emergencies (p = 0.001). For psychiatric patients who refused medically indicated inpatient psychiatric admission ("involuntary psychiatric admission"), male and female emergency physicians were equally likely to take the required action (p = 0.522). However, male emergency physicians were significantly more likely to administer an intravenous hypnotic to enforce involuntary admission (p = 0.009). CONCLUSIONS: Similar to other medical specialties where the influence of physician gender on patient care is certainly relevant, the gender of prehospital emergency physicians also appears to influence their prehospital management strategy in psychiatric emergencies. The influence of gender is sometimes subtle and limited to specific aspects, such as the administration of hypnotics. Prospective study designs are needed to thoroughly investigate the influence of the gender of the prehospital emergency physician on the quality of care in psychiatric emergencies. TRIAL REGISTRATION: The study was approved by the ethics committee of the University Ulm, Trial-Code No. 110/22 and was prospectively registered in the German Clinical Trials Register (DRKS-ID: DRKS00031237). Patient information was not required for retrospective data analysis.

Mechanical trauma in children and adolescents in Berlin.

Management of severe pediatric trauma remains challenging. Injury patterns vary according to patient age and trauma mechanism. This study analyzes trauma mechanisms in deceased pediatric patients. Fatal pediatric trauma cases aged 0-18 years who underwent forensic autopsy in the Federal State of Berlin, Germany, between 2008 until 2018 were enrolled in this retrospective study. Autopsy protocols were analyzed regarding demographic characteristics, trauma mechanisms, injury patterns, resuscitation measures, survival times as well as place, and cause of death. 71 patients (73% male) were included. Traffic accidents (40%) were the leading cause of trauma, followed by falls from height > 3 m (32%), railway accidents (13%), third party violence (11%) and other causes (4%). While children under 14 years of age died mostly due to traumatic brain injury (59%), polytrauma was the leading cause of death in patients > 14 years (55%). Other causes of death were hemorrhage (9%), thoracic trauma (1%) or other (10%). A suicidal background was proven in 24%. In the age group of > 14 years, 40% of all mortalities were suicides. Cardiopulmonary resuscitation was carried out in 39% of all patients. 42% of the patients died at the scene. Children between 0 and 14 years of age died most frequently from traumatic brain injury. In adolescents between 14 and 18 years of age, polytrauma was mostly the cause of death with a high coincidence of suicidal deaths. The frequency of fatal traffic accidents and suicides shows the need to improve accident and suicide prevention for children and adolescents.

[Interhospital critical care transport]. / Interhospitaler Intensivtransport.

Critically ill patients in need of specialized diagnostic or therapeutic procedures, but are being cared for in a hospital without such equipment, have to be transferred to appropriate centers without discontinuation of current critical care (interhospital critical care transfer). These transfers are resource intensive, challenging, and require high logistical effort, which must be managed by a specialized and highly trained team, predeployment planning and efficient crew-resource management strategies. If planned adequately, interhospital critical care transfers can be performed safely without frequent adverse events. Beside routine interhospital critical care transfers, there are special missions (e.g., for patients in quarantine or supported by extracorporeal organ support) that might require adaption of the team composition or standard equipment. This article describes interhospital critical care transport missions including their different phases and special circumstances.

[Prehospital treatment of tension pneumothorax in children-which decisions do we make? : Results of a survey among German emergency physicians]. / Die prähospitale Therapie eines Spannungspneumothorax bei Kindern ­ welche Entscheidungen treffen wir? : Ergebnisse einer Umfrage unter deutschen Notärzten.

BACKGROUND: The preclinical treatment of a traumatic or spontaneous tension pneumothorax remains a particular challenge in pediatric patients. Currently recommended interventions for decompression are either finger thoracostomy or needle decompression. Due to the tiny intercostal spaces, finger thoracostomy may not be feasible in small children and surgical preparation may be necessary. In needle decompression, the risk of injuring underlying vital structures is increased because of the smaller anatomic structures. As most emergency physicians do not regularly work in pediatric trauma care, decompression of tension pneumothorax is associated with significant uncertainty; however, in this rare emergency situation, consistent and goal-oriented action is mandatory and lifesaving. An assessment of pre-existing experience and commonly used techniques therefore seems necessary to deduce the need for future education and training. OBJECTIVE: In this study an online survey was created to evaluate the experience and the favored prehospital treatment of tension pneumothorax in children among German emergency physicians. MATERIAL AND METHODS: An online survey was conducted with 43 questions on previous experience with tension pneumothorax in children, favored decompression technique and anatomical structures in different age groups. Surveyed were the emergency physicians of the ground-based emergency medical service of the University Medical Center Mannheim, the German Air Rescue Service (DRF) and the pediatric emergency medical service of the City of Munich. RESULTS: More than half of all respondents stated that there was uncertainty about the procedure of choice. Needle decompression was favored in smaller children and mini-thoracostomy in older children. In comparison with the literature, the thickness of the chest wall was mostly estimated correctly by the emergency medical physicians. The depth of the vital structures was underestimated at most of the possible insertion sites in all age groups. At the lateral insertion sites on the left hemithorax, however, the distance to the left ventricle was overestimated. The caliber of the needle selected for decompression tended to be too large, especially in younger children. CONCLUSION: Even though having interviewed an experienced group of prehospital emergency physicians, the experience in decompression of tension pneumothorax in children is relatively scant. Knowledge of chest wall thickness and depth to vital structures is sufficient, the choice of needle calibers tends to be too large but still reasonable. For many providers a large amount of uncertainty about the right choice of technique and equipment arises from the challenge of decompressing a tension pneumothorax in children and therefore further theoretical education and regular training are required for safe performance of the procedure.

Video-based, student tutor- versus faculty staff-led ultrasound course for medical students - a prospective randomized study.

BACKGROUND: Ultrasound education is propagated already during medical school due to its diagnostic importance. Courses are usually supervised by experienced faculty staff (FS) with patient bedside examinations or students among each other but often overbooked due to limited FS availability. To overcome this barrier, use of teaching videos may be advantageous. Likewise, peer teaching concepts solely with trained student tutors have shown to be feasible and effective. The aim was to evaluate 1) objective learning outcomes of a combined video-based, student-tutor (ViST) as compared to a FS-led course without media support, 2) acceptance and subjective learning success of the videos. METHODS: Two ultrasound teaching videos for basic and advanced abdominal ultrasound (AU) and transthoracic echocardiography (TTE) were produced and six students trained as tutors. Fourth-year medical students (N = 96) were randomized to either the ViST- or FS course (6 students per tutor). Learning objectives were defined equally for both courses. Acquired practical basic and advanced ultrasound skills were tested in an objective structured clinical examination (OSCE) using modified validated scoring sheets with a maximum total score of 40 points. Acceptance and subjective learning success of both videos were evaluated by questionnaires based on Kirkpatrick's evaluation model with scale-rated closed and open questions. RESULTS: 79 of 96 medical students completed the OSCE and 77 could be finally analyzed. There was no significant difference in the mean total point score of 31.3 in the ViST (N = 42) and 32.7 in the FS course (N = 35, P = 0.31) or in any of the examined basic or advanced ultrasound skill subtasks. Of the 42 ViST participants, 29 completed the AU and 27 the TTE video questionnaire. Acceptance and subjective learning success of both videos was rated positively in 14-52% and 48-88% of the rated responses to each category, respectively. Attendance of either the student or faculty tutor was deemed necessary in addition to the videos. CONCLUSIONS: A ViST versus FS teaching concept was able to effectively teach undergraduate students in AU and TTE, albeit acceptance of the teaching videos alone was limited. However, the ViST concept has the potential to increase course availability and FS resource allocation.

Adjustment of positive end-expiratory pressure to body mass index during mechanical ventilation in general anesthesia: BodyVent, a randomized controlled trial.

BACKGROUND: In patients requiring general anesthesia, lung-protective ventilation can prevent postoperative pulmonary complications, which are associated with higher morbidity, mortality, and prolonged hospital stay. Application of positive end-expiratory pressure (PEEP) is one component of lung-protective ventilation. The correct strategy for setting adequate PEEP, however, remains controversial. PEEP settings that lead to a lower pressure difference between end-inspiratory plateau pressure and end-expiratory pressure ("driving pressure," ΔP) may reduce the risk of postoperative pulmonary complications. Preliminary data suggests that the PEEP required to prevent both end-inspiratory overdistension and end-expiratory alveolar collapse, thereby reducing ΔP, correlates positively with the body mass index (BMI) of patients, with PEEP values corresponding to approximately 1/3 of patient's respective BMI. Thus, we hypothesize that adjusting PEEP according to patient BMI reduces ΔP and may result in less postoperative pulmonary complications. METHODS: Patients undergoing general anesthesia and endotracheal intubation with volume-controlled ventilation with a tidal volume of 7 ml per kg predicted body weight will be randomized and assigned to either an intervention group with PEEP adjusted according to BMI or a control group with a standardized PEEP of 5 mbar. Pre- and postoperatively, lung ultrasound will be performed to determine the lung aeration score, and hemodynamic and respiratory vital signs will be recorded for subsequent evaluation. The primary outcome is the difference in ΔP as a surrogate parameter for lung-protective ventilation. Secondary outcomes include change in lung aeration score, intraoperative occurrence of hemodynamic and respiratory events, oxygen requirements and postoperative pulmonary complications. DISCUSSION: The study results will show whether an intraoperative ventilation strategy with PEEP adjustment based on BMI has the potential of reducing the risk for postoperative pulmonary complications as an easy-to-implement intervention that does not require lengthy ventilator maneuvers nor additional equipment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00031336. Registered 21st February 2023. TRIAL STATUS: The study protocol was approved by the ethics committee of the Christian-Albrechts-Universität Kiel, Germany, on 1st February 2023. Recruitment began in March 2023 and is expected to end in September 2023.

Pulmonary function testing in preoperative high-risk patients.

BACKGROUND: Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes. METHODS: A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET < 4) were examined. Clinical characteristics, history of lung diseases, and smoking status were also recorded. The statistical analysis entailed t-tests, one-way ANOVA, and multiple linear regression with backward elimination for group comparisons. RESULTS: Among 256 included patients, 230 fulfilled the test quality criteria. Eighty-one (35.2%) patients presented obstructive ventilatory disorders, out of which 65 were previously unknown. 38 of the newly diagnosed obstructive disorders were mild, 18 moderate, and 9 severe. One hundred forty-five DLCO measurements revealed 40 (27.6%) previously unknown gas exchange impairments; 21 were mild, 17 moderate, and 2 severe. The pulmonary function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly lower than the international reference values of a healthy population. Patients with a lower ASA class and no history of smoking exhibited higher FVC, FEV1, and DLCO values. Reduced exercise tolerance with MET < 4 was strongly associated with lower spirometry values. CONCLUSIONS: Our screening program detected a relevant number of patients with previously unknown obstructive ventilatory disorders and impaired pulmonary gas exchange. This newly discovered sickness is associated with low metabolic equivalents and may influence perioperative outcomes. Whether optimized management of patients with previously unknown impaired lung function leads to a better outcome should be evaluated in multicenter studies. TRIAL REGISTRATION: German Registry of Clinical Studies (DRKS00029337), registered on: June 22nd, 2022.

[Physician-assisted interhospital transfer-an analysis from Schleswig-Holstein]. / Arztbegleitete Interhospitaltransporte ­ eine Analyse aus Schleswig-Holstein.

BACKGROUND: The need for interhospital transport (IHT) of intensive care patients is increasing due to changes in the hospital environment. Interhospital transports are challenging and require careful operational planning of personnel and rescue vehicles. OBJECTIVE: To investigate the need for IHT, an analysis was conducted in the service area of the emergency medical service central dispatch center (IRLS) in Schleswig-Holstein. MATERIAL AND METHODS: Emergency physician-assisted IHT were analyzed in the period from 01.10.2021 to 30.09.2022. RESULTS: Of a total of 158,823 documented IRLS missions, 2264 (1.4%) records could be identified and included as IHT: 1389 IHT (61.4%) were managed by specialized ambulances, 875 (38.6%) by primary care ambulances. Primary care ambulances were mainly used for time-critical transfers and outside the duty hours of the intensive care ambulances, 21.2 % were by air. Of all IHT, 43.1% were required to hospitals with a higher level of medical care. CONCLUSION: Emergency physician-assisted IHT are a relevant part of the emergency service's operational spectrum and concern both primary care and specialized rescue vehicles. A relevant number of urgent IHT were recorded outside the duty hours of the intensive care ambulances. For emergency transports during nighttime, an expansion of air-based transfer capacities should be considered due to the time advantage. For less urgent IHT, an adjustment of the capacities of specialized ground-based vehicles in Schleswig-Holstein seems reasonable.

The role of PEEP for cannulation of the subclavian vein: A prospective observational study.

PURPOSE: The role of positive endexpiratory pressure (PEEP) for successful cannulation of the subclavian vein (SCV) remains inconclusive. The aim of our study was to assess the effect of different levels of PEEP on distance from SCV to parietal pleura (DVP) and on the cross-sectional area (CSA) of the SCV. METHODS: Invasive mechanically ventilated adult patients with a clinical indication for a stepwise PEEP-trial (0, 5, 10, and 15 cm H2O) were included in this prospective observational single-center study. Ultrasound examinations of SCV were performed with a linear ultrasound probe using the infraclavicular view. DVP and CSA were measured on the right and left bodyside. Examinations were repeated at each PEEP step. RESULTS: 27 patients were enrolled (12 female; 60±21 years; BMI 24.6±4.9 kg/m2; 20 patients on controlled, 7 on assisted ventilation). A statistically significant increase of DVP in the in-plane view was found on the left side which was not clinically relevant. No significant differences of DVP were observed in all other views. PEEP induced changes in CSAs were statistically significant but clinically not relevant on both sides. The largest change in CSA (2mm2) was observed when comparing PEEP 10 with PEEP 0 cm H2O. CONCLUSION: A stepwise PEEP increase was not associated with clinically relevant changes of the DVP and CSA. Thus, a PEEP-optimization for the cannulation of the subclavian vein is not indicated.

[Interhospital critical care transport]. / Interhospitaler Intensivtransport.

Critically ill patients in need of specialized diagnostic or therapeutic procedures, but are being cared for in a hospital without such equipment, have to be transferred to appropriate centers without discontinuation of current critical care (interhospital critical care transfer). These transfers are resource intensive, challenging, and require high logistical effort, which must be managed by a specialized and highly trained team, predeployment planning and efficient crew-resource management strategies. If planned adequately, interhospital critical care transfers can be performed safely without frequent adverse events. Beside routine interhospital critical care transfers, there are special missions (e.g., for patients in quarantine or supported by extracorporeal organ support) that might require adaption of the team composition or standard equipment. This article describes interhospital critical care transport missions including their different phases and special circumstances.

Pre-hospital analgesia in pediatric trauma and critically ill patients: An analysis of a German air rescue service.

BACKGROUND: Pain management in the pre-hospital setting remains a particular challenge for paramedics and emergency physicians, especially in children. This study evaluates the pre-hospital use and effect of analgesics in children with trauma or pain due to other reasons. METHODS: This study is a retrospective analysis of the database of a German air rescue service and was conducted over a period of 9 years (2012-2020) to assess pain in general and whether patients with trauma pain due to other reasons received treatment with analgesics. We included all patients in the registry under the age of 16 years. Patients with a Glasgow Coma Scale of 3 at hospital admission and incomplete records were excluded. The intensity of pain was determined by the emergency physician on scene at arrival and hospital admission in a ten-point rating scale (0 = no pain). Effective pain reduction was analyzed. RESULTS: Out of 227,458 cases, a total of 22,025 emergency cases involved pediatric patients aged 0-16 years. 20,405 cases were included in the study. 12,000 (58.8%) children had suffered a trauma, 8108 (39.7%) had pain due to other reasons and 297 (1.5%) had both. In total, 4,608 (38.4%) of the children with trauma were assessed having a numerical rating scale (NRS) > 4 at EMS arrival. These patients received mainly ketamine (34.5%) and the opioids fentanyl (38.7%) and piritramide (19.1%). The value on the NRS was significantly lower at admission to hospital (mean 1.9) compared with the EMS arrival (mean 6.9). In 4.9% the NRS at hospital admission was still > 4. 282 patients within the non-trauma group had a pre-hospital NRS of > 4. The pain therapy consisted of opioids (35.8%) and ketamine (2.8%). 28.4% patients in the non-trauma group received no pain medication. In 16.0% the NRS at hospital admission was still > 4. CONCLUSIONS: German emergency physicians achieved a sufficient pain therapy in pediatric patients with a NRS > 4 after trauma. In case of non-trauma, the pain management by the emergency physicians is restrained and less successful. The most common analgesic medications administered were ketamine and fentanyl, followed by piritramide. TRIAL REGISTRATION: The study has been retrospectively registered at DRKS (DRKS00026222).

Large extracellular vesicles derived from human regulatory macrophages (L-EVMreg) attenuate CD3/CD28-induced T-cell activation in vitro.

Macrophages belong to the innate immune system, and we have recently shown that in vitro differentiated human regulatory macrophages (Mreg) release large extracellular vesicles (L-EVMreg) with an average size of 7.5 µm which regulate wound healing and angiogenesis in vitro. The aim of this study was to investigate whether L-EVMreg also affect the CD3/CD28-mediated activation of T-cells. Mreg were differentiated using blood monocytes and L-EVMreg were isolated from culture supernatants by differential centrifugation. Activation of human T-cells was induced by CD3/CD28-coated beads in the absence or presence of Mreg or different concentrations of L-EVMreg. Inhibition of T-cell activation was quantified by flow cytometry and antibodies directed against the T-cell marker granzyme B. Phosphatidylserine (PS) exposure on the surface of Mreg and L-EVMreg was analyzed by fluorescence microscopy. Incubation of human lymphocytes with CD3/CD28 beads resulted in an increase of cell size, cell granularity, and number of granzyme B-positive cells (P < 0.05) which is indicative of T-cell activation. The presence of Mreg (0.5 × 106 Mreg/ml) led to a reduction of T-cell activation (number of granzyme B-positive cells; P < 0.001), and a similar but less pronounced effect was also observed when incubating activated T-cells with L-EVMreg (P < 0.05 for 3.2 × 106 L-EVMreg/ml). A differential analysis of the effects of Mreg and L-EVMreg on CD4+ and CD8+ T-cells showed an inhibition of CD4+ T-cells by Mreg (P < 0.01) and L-EVMreg (P < 0.05 for 1.6 × 106 L-EVMreg/ml; P < 0.01 for 3.2 × 106 L-EVMreg/ml). A moderate inhibition of CD8+ T-cells was observed by Mreg (P < 0.05) and by L-EVMreg (P < 0.01 for 1.6 × 106 L-EVMreg/ml and 3.2 × 106 L-EVMreg/ml). PS was restricted to confined regions of the Mreg surface, while L-EVMreg showed strong signals for PS in the exoplasmic leaflet. L-EVMreg attenuate CD3/CD28-mediated activation of CD4+ and CD8+ T-cells. L-EVMreg may have clinical relevance, particularly in the treatment of diseases associated with increased T-cell activity. KEY MESSAGES: Mreg release large extracellular vesicles (L-EVMreg) with an average size of 7.5 µm L-EVMreg exhibit phosphatidylserine positivity L-EVMreg suppress CD4+ and CD8+ T-cells L-EVMreg hold clinical potential in T-cell-related diseases.

[Ethical aspects of mechanical resuscitation in a child : Results of an expert workshop within the BMBF project CLAIRE-Children's Automated Intelligent Resuscitation]. / Ethische Aspekte mechanischer Reanimationshilfen beim Kind : Ergebnisse eines Expertenworkshops im Rahmen des BMBF-Projekts CLAIRE ­ Children's Automated Intelligent Resuscitation.

BACKGROUND: While the use of mechanical resuscitation devices can be considered for adult resuscitation, the European Resuscitation Council guidelines do not yet mention their use for pediatric resuscitation. Only one device has been partially approved for use in children; further pediatric appliances are currently being used off-label. Ethical considerations arising from the use of mechanical resuscitation devices have not yet been presented in a structured way. OBJECTIVE: To elaborate ethical considerations in the development phase of mechanical resuscitation devices for children. METHODS: Based on several fictitious case reports, an interdisciplinary expert focus group discussion was conducted. This was followed by a moderated discussion, summarizing the results. Guiding principles and research desiderata were formulated using these results as well as existing literature. RESULTS: According to the group of experts, ethical considerations regarding mechanical resuscitation devices in pediatrics predominantly concern the subject of indication and discontinuation criteria. Ethical aspects concerning psychosocial impacts on affected families and intervention teams cannot be generalized and need to be analyzed on a case-by-case basis. CONCLUSION: The considerations presented regarding the use of mechanical resuscitation devices in the pediatric context, which is still in its developmental stage, could also have practical implications for adult out-of-hospital resuscitation decisions. Concerning ethical aspects of out-of-hospital resuscitation decisions, especially using mechanical resuscitation devices, the need for accompanying empirical research is substantial.

[Ultrasound diagnostics in prehospital emergency care-do we need a standardized educational approach?] / Ultraschalldiagnostik in der prähospitalen Notfallmedizin ­ brauchen wir eine standardisierte Ausbildung?

BACKGROUND: Limited diagnostic capabilities represent an ongoing obstacle in out-of-hospital emergency settings. Prehospital deployment of ultrasound might reduce this particular diagnostic gap. So far, little is known about the availability and usage of ultrasound in emergency medical services (EMS) or about the level of education of EMS physicians regarding prehospital ultrasound (point-of-care ultrasound, POCUS). METHODS: A nationwide survey was conducted among emergency physicians in Germany focusing on POCUS education and experience. RESULTS: Between 02/2022 and 05/2022, 1079 responses were registered, of which 853 complete responses were analyzed. Of the emergency physicians, 71.9% consider POCUS beneficial for out-of-hospital diagnostics and 43.8% had participated in a certified POCUS training prior to the survey. The self-evaluation of POCUS skills among emergency physicians depended significantly on their participation in a certified training (p < 0.001) and frequent ultrasound routine (p < 0.001). CONCLUSION: The majority of participating emergency physicians in Germany consider POCUS to improve out-of-hospital diagnostic capabilities. Participation in a certified POCUS training and frequent use of ultrasound facilitated higher self-confidence in POCUS skills.