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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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. In the present study ASL was feasible to detect anesthesia-related changes in cerebral perfusion, in line with Venkatraghavan.[9] Nevertheless, it would be beneficial to improve spatial resolution to determine CBF also in deeper brain regions such as the basal ganglia/hippocampus. [Extracted from the article]

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., (© 2024. The Author(s).)

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., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)