Purpose: A nationwide study (2012-2017) of preventable trauma death rates (PTDR) showed a 15.3% decrease after Regional Trauma centers were initiated. However, in non-trauma centers with an Emergency Department there is limited data of preventable mortality in trauma patients. Therefore, the purpose of this retrospective study was to investigate preventable mortality in trauma patients in a nonregional trauma center and determine the effect of initiating a Trauma Team. Methods: There were 46 deaths of trauma patients recorded in the National Health Insurance service Ilsan Hospital (NHISIH) in South Korea from January 2019 to December 2021. These patients’ preventable deaths were analyzed by an expert panel review considering the implementation of the Trauma Team in April 2020. Results: All deaths were attributable to blunt trauma with an average Injury Severity Score of 26.0 ± 19.2, Revised Trauma Score of 5.05 ± 3.20 and Trauma and Injury Score of 56.6 ± 41.3. The most frequent cause of death was traumatic brain injury followed by respiratory arrest. The most frequent error was delayed transfusion followed by delayed treatment of bleeding. Treatment errors occurred the most in the Emergency Room followed by the Intensive Care Unit. The PTDR of patients before the involvement of a Trauma Team (January 2019 to March 2020) and after the Trauma Team was initiated in April 2020 decreased from 27.27% to 4.27%, respectively (p = 0.021). Conclusion The introduction of a dedicated Trauma Team in a non-regional trauma center significantly reduced the overall PTDR in trauma patients.

Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) has emerged as an innovative immunotherapy for hematological cancer treatment. However, the limited effect on solid tumors, complex processes, and excessive manufacturing costs remain as limitations of CAR-T therapy. Nanotechnology provides an alternative to the conventional CAR-T therapy. Owing to their unique physicochemical properties, nanoparticles can not only serve as a delivery platform for drugs but also target specific cells. Nanoparticle-based CAR therapy can be applied not only to T cells but also to CAR-natural killer and CAR-macrophage, compensating for some of their limitations. This review focuses on the introduction of nanoparticle-based advanced CAR immune cell therapy and future perspectives on immune cell reprogramming.

Background: Inflammation induces dysfunction of endothelial cells via inflammatory cell adhesion, and this phenomenon and reactive oxygen species accumulation are pivotal triggers for atherosclerosis-related vascular disease. Although exosomes are excellent candidate as an inhibitor in the inflammation pathway, it is necessary to develop exosome-mimetic nanovesicles (NVs) due to limitations of extremely low release rate and difficult isolation of natural exosomes. NVs are produced in much larger quantities than natural exosomes, but due to the low flexibility of the cell membranes, the high loss caused by hanging on the filter membranes during extrusion remains a challenge to overcome. Therefore, by making cell membranes more flexible, more efficient production of NVs can be expected. Methods: To increase the flexibility of the cell membranes, the suspension of umbilical cord-mesenchymal stem cells (UC-MSCs) was subjected to 5 freeze and thaw cycles (FT) before serial extrusion. After serial extrusion through membranes with three different pore sizes, FT/NVs were isolated using a tangential flow filtration (TFF) system. NVs or FT/NVs were pretreated to the human coronary artery endothelial cells (HCAECs), and then inflammation was induced using tumor necrosis factor-α (TNF-α). Results: With the freeze and thaw process, the production yield of exosome-mimetic nanovesicles (FT/NVs) was about 3 times higher than the conventional production method. The FT/NVs have similar biological properties as NVs for attenuating TNF-α induced inflammation. Conclusion We proposed the efficient protocol for the production of NVs with UC-MSCs using the combination of freeze and thaw process with a TFF system. The FT/NVs successfully attenuated the TNF-α induced inflammation in HCAECs.

BACKGROUND: Poly(lactic-co-glycolic acid) (PLGA) microspheres have been actively used in various pharmaceutical formulations because they can sustain active pharmaceutical ingredient release and are easy to administer into the body using a syringe. However, the acidic byproducts produced by the decomposition of PLGA cause inflammatory reactions in surrounding tissues, limiting biocompatibility. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive because it has an acid-neutralizing effect. METHODS: To improve the encapsulation efficiency of hydrophilic MH, the MH particles were capped with hydrophobic ricinoleic acid (RA-MH). PLGA microspheres encapsulated with RA-MH particles were manufactured by the O/W method. To assess the in vitro cytotoxicity of the degradation products of PLGA, MH/PLGA, and RA-MH/PLGA microspheres, CCK-8 and Live/Dead assays were performed with NIH-3T3 cells treated with different concentrations of their degradation products. in vitro anti-inflammatory effect of RA-MH/PLGA microspheres was evaluated with quantitative measurement of pro-inflammatory cytokines. RESULTS: The synthesized RA-MH was encapsulated in PLGA microspheres and displayed more than four times higher loading content than pristine MH. The PLGA microspheres encapsulated with RA-MH had an acid-neutralizing effect better than that of the control group. In an in vitro cell experiment, the degradation products obtained from RA-MH/PLGA microspheres exhibited higher biocompatibility than the degradation products obtained from PLGA microspheres. Additionally, the RA-MH/PLGA microsphere group showed an excellent anti-inflammatory effect. CONCLUSION Our results proved that RA-MH-encapsulated PLGA microspheres showed excellent biocompatibility with an anti-inflammatory effect. This technology can be applied to drug delivery and tissue engineering to treat various incurable diseases in the future.

BACKGROUND: Poly(lactic-co-glycolic acid) (PLGA) microspheres have been actively used in various pharmaceutical formulations because they can sustain active pharmaceutical ingredient release and are easy to administer into the body using a syringe. However, the acidic byproducts produced by the decomposition of PLGA cause inflammatory reactions in surrounding tissues, limiting biocompatibility. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive because it has an acid-neutralizing effect. METHODS: To improve the encapsulation efficiency of hydrophilic MH, the MH particles were capped with hydrophobic ricinoleic acid (RA-MH). PLGA microspheres encapsulated with RA-MH particles were manufactured by the O/W method. To assess the in vitro cytotoxicity of the degradation products of PLGA, MH/PLGA, and RA-MH/PLGA microspheres, CCK-8 and Live/Dead assays were performed with NIH-3T3 cells treated with different concentrations of their degradation products. in vitro anti-inflammatory effect of RA-MH/PLGA microspheres was evaluated with quantitative measurement of pro-inflammatory cytokines. RESULTS: The synthesized RA-MH was encapsulated in PLGA microspheres and displayed more than four times higher loading content than pristine MH. The PLGA microspheres encapsulated with RA-MH had an acid-neutralizing effect better than that of the control group. In an in vitro cell experiment, the degradation products obtained from RA-MH/PLGA microspheres exhibited higher biocompatibility than the degradation products obtained from PLGA microspheres. Additionally, the RA-MH/PLGA microsphere group showed an excellent anti-inflammatory effect. CONCLUSION Our results proved that RA-MH-encapsulated PLGA microspheres showed excellent biocompatibility with an anti-inflammatory effect. This technology can be applied to drug delivery and tissue engineering to treat various incurable diseases in the future.