Human Muse cells isolated from preterm- and term-umbilical cord delivered therapeutic effects in rat bleomycin-induced lung injury model without immunosuppressant.

BACKGROUND: Bleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients with bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Although no curative therapies for these lung diseases exist, stem cell therapy has emerged as a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- and macrophage-like stem cells distributed in various adult and fetal tissues as stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue by sensing sphingosine-1-phosphate and replace the damaged/apoptotic cells by in vivo differentiation. Clinical trials for some human diseases suggest the safety and therapeutic efficacy of intravenously injected human leukocyte antigen-mismatched allogenic Muse cells from adult bone marrow (BM) without immunosuppressant. Here, we evaluated the therapeutic effects of human Muse cells from preterm and term umbilical cord (UC), and adult BM in a rat BLM-induced lung injury model. METHODS: Rats were endotracheally administered BLM to induce lung injury on day 0. On day 3, human preterm UC-Muse, term UC-Muse, or adult BM-Muse cells were administered intravenously without immunosuppressants, and rats were subjected to histopathologic analysis on day 21. Body weight, serum surfactant protein D (SP-D) levels, and oxygen saturation (SpO2) were monitored. Histopathologic lung injury scoring by the Ashcroft and modified American Thoracic Society document scales, quantitative characterization of engrafted Muse cells, RNA sequencing analysis, and in vitro migration assay of infused Muse cells were performed. RESULTS: Rats administered preterm- and term-UC-Muse cells exhibited a significantly better recovery based on weight loss, serum SP-D levels, SpO2, and histopathologic lung injury scores, and a significantly higher rate of both Muse cell homing to the lung and alveolar marker expression (podoplanin and prosurfactant protein-C) than rats administered BM-Muse cells. Rats receiving preterm-UC-Muse cells showed statistically superior results to those receiving term-UC-Muse cells in many of the measures. These findings are thought to be due to higher expression of genes related to cell migration, lung differentiation, and cell adhesion. CONCLUSION: Preterm UC-Muse cells deliver more efficient therapeutic effects than term UC- and BM-Muse cells for treating BLM-induced lung injury in a rat model.

Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

A Comparison of Tube Thoracostomy for Chest Trauma Between Prehospital and Inhospital Settings.

OBJECTIVE: We compared the outcomes of patients with tube thoracostomy for chest trauma between the prehospital and inhospital settings. METHODS: The subjects were then divided into 2 groups: the prehospital group, which included subjects who underwent tube thoracostomy in the prehospital setting, and the inhospital group, which included subjects who underwent tube thoracostomy in the inhospital setting. The variables were compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups with regard to gender, age, history, mechanism of injury, infusion of antibiotics, white blood cell count, duration of insertion of a chest drain, mechanical ventilation, complication of drain infection, duration of admission, or final outcome. However, the Injury Severity Score, maximum C-reactive protein level, and maximum temperature during hospitalization in the prehospital group (n = 15) were significantly greater than those in the inhospital group (n = 119). CONCLUSION: The present study suggested that thoracostomy performed by physicians in the prehospital setting was safe and did not have an increased risk of infection. In addition, thoracostomy for chest injury in the prehospital setting suggested an improvement in the likelihood of a survival outcome.

Single-cell RNA sequencing reveals different signatures of mesenchymal stromal cell pluripotent-like and multipotent populations.

Somatic stem cells are advantageous research targets for understanding the properties required to maintain stemness. Human bone marrow-mesenchymal stromal cells (BM-MSCs) were separated into pluripotent-like SSEA-3(+) Muse cells (Muse-MSCs) and multipotent SSEA-3(-) MSCs (MSCs) and were subjected to single-cell RNA sequencing analysis. Compared with MSCs, Muse-MSCs exhibited higher expression levels of the p53 repressor MDM2; signal acceptance-related genes EGF, VEGF, PDGF, WNT, TGFB, INHB, and CSF; ribosomal protein; and glycolysis and oxidative phosphorylation. Conversely, MSCs had higher expression levels of FGF and ANGPT; Rho family and caveola-related genes; amino acid and cofactor metabolism; MHC class I/II, and lysosomal enzyme genes than Muse-MSCs. Unsupervised clustering further divided Muse-MSCs into two clusters stratified by the expression of cell cycle-related genes, and MSCs into three clusters stratified by the expression of cell cycle-, cytoskeleton-, and extracellular matrix-related genes. This study evaluating the differentiation ability of BM-MSC subpopulations provides intriguing insights for understanding stemness.

Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia.

Cell-based therapies hold great promise for the treatment of peripheral arterial disease (PAD), especially in patients presenting with severe limb ischemia, although the optimal strategy remains to be explored. In this study, we evaluated the therapeutic effect of intravenous administration of human Muse cells, a unique subpopulation of mesenchymal stem cells (MSC), using a mouse model of hindlimb ischemia (HLI) without an immunosuppressant. Compared with the phosphate buffered saline (PBS) or non-Muse MSC groups, the Muse group showed significantly higher laser doppler blood flow in the ischemic limb at days 7 and 14 after HLI. Increased microvascular density [percent area of CD31(+) cells] and reduced interstitial fibrosis in the ischemic limb muscle were also observed in the Muse group. mCherry-expressing Muse cells were found in the ischemic border zone and expressed CD31 but did not in the non-ischemic limb. Muse cells produced higher amounts of vascular endothelial growth factor (VEGF) than non-Muse cells under normoxic and hypoxic conditions in vitro. In the ischemic muscle, tissue VEGF concentration and angiogenesis-related genes such as Vegfa, Angpt1, Pdgfb, and Igf1 were significantly higher in the Muse group than in the other two groups. In addition, the proportion of M2 macrophages to total macrophages and the ratio of anti-inflammatory-related genes such as IL-10, Arg1, and CD206 per iNOS were significantly higher in the Muse group than in the other two groups. In summary, Muse cells exert pleiotropic effects in a mouse model of HLI, and therefore may provide a novel therapeutic approach for the treatment of PAD patients with severe limb ischemia.

Phagocytosing differentiated cell-fragments is a novel mechanism for controlling somatic stem cell differentiation within a short time frame.

Stem cells undergo cytokine-driven differentiation, but this process often takes longer than several weeks to complete. A novel mechanism for somatic stem cell differentiation via phagocytosing 'model cells' (apoptotic differentiated cells) was found to require only a short time frame. Pluripotent-like Muse cells, multipotent mesenchymal stem cells (MSCs), and neural stem cells (NSCs) phagocytosed apoptotic differentiated cells via different phagocytic receptor subsets than macrophages. The phagocytosed-differentiated cell-derived contents (e.g., transcription factors) were quickly released into the cytoplasm, translocated into the nucleus, and bound to promoter regions of the stem cell genomes. Within 24 ~ 36 h, the cells expressed lineage-specific markers corresponding to the phagocytosed-differentiated cells, both in vitro and in vivo. At 1 week, the gene expression profiles were similar to those of the authentic differentiated cells and expressed functional markers. Differentiation was limited to the inherent potential of each cell line: triploblastic-, adipogenic-/chondrogenic-, and neural-lineages in Muse cells, MSCs, and NSCs, respectively. Disruption of phagocytosis, either by phagocytic receptor inhibition via small interfering RNA or annexin V treatment, impeded differentiation in vitro and in vivo. Together, our findings uncovered a simple mechanism by which differentiation-directing factors are directly transferred to somatic stem cells by phagocytosing apoptotic differentiated cells to trigger their rapid differentiation into the target cell lineage.

Naïve pluripotent-like characteristics of non-tumorigenic Muse cells isolated from human amniotic membrane.

Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent-like stem cells that exhibit triploblastic differentiation and self-renewability at the single-cell level, and are collectable as pluripotent surface marker SSEA-3(+) from the bone marrow (BM), peripheral blood, and organ connective tissues. SSEA-3(+) cells from human amniotic membrane mesenchymal stem cells (hAMSCs) were compared with hBM-Muse cells. Similar to hBM-Muse cells, hAMSC-SSEA-3(+) cells expressed pluripotency genes (OCT3/4, NANOG, and SOX2), differentiated into triploblastic cells from a single cell, self-renewed, and exhibited non-tumorigenicity. Notably, however, they exhibited unique characteristics not seen in hBM-Muse cells, including higher expression of genes related to germline- and extraembryonic cell-lineages compared with those in hBM-Muse cells in single-cell RNA-sequencing; and enhanced expression of markers relevant to germline- (PRDM14, TFAP2C, and NANOS3) and extraembryonic cell- (CDX2, GCM1, and ID2) lineages when induced by cytokine subsets, suggesting a broader differentiation potential similar to naïve pluripotent stem cells. t-SNE dimensionality reduction and Gene ontology analysis visualized hAMSC-SSEA-3(+) cells comprised a large undifferentiated subpopulation between epithelial- and mesenchymal-cell states and a small mesenchymal subpopulation expressing genes relevant to the placental formation. The AM is easily accessible by noninvasive approaches. These unique cells are a potentially interesting target naïve pluripotent stem cell-like resource without tumorigenicity.

Inhibition of Gap Junctional Intercellular Communication Upregulates Pluripotency Gene Expression in Endogenous Pluripotent Muse Cells.

Gap junctions (GJ) are suggested to support stem cell differentiation. The Muse cells that are applied in clinical trials are non-tumorigenic pluripotent-like endogenous stem cells, can be collected as stage-specific embryonic antigen 3 (SSEA-3+) positive cells from multiple tissues, and show triploblastic differentiation and self-renewability at a single cell level. They were reported to up-regulate pluripotency gene expression in suspension. We examined how GJ inhibition affected pluripotency gene expression in adherent cultured-Muse cells. Muse cells, mainly expressing gap junction alpha-1 protein (GJA1), reduced GJ intercellular communication from ~85% to 5-8% after 24 h incubation with 120 µM 18α-glycyrrhetinic acid, 400 nM 12-O-tetradecanoylphorbol-13-acetate, and 90 µM dichlorodiphenyltrichloroethane, as confirmed by a dye-transfer assay. Following inhibition, NANOG, OCT3/4, and SOX2 were up-regulated 2-4.5 times more; other pluripotency-related genes, such as KLF4, CBX7, and SPRY2 were elevated; lineage-specific differentiation-related genes were down-regulated in quantitative-PCR and RNA-sequencing. Connexin43-siRNA introduction also confirmed the up-regulation of NANOG, OCT3/4, and SOX2. YAP, a co-transcriptional factor in the Hippo signaling pathway that regulates pluripotency gene expression, co-localized with GJA1 (also known as Cx43) in the cell membrane and was translocated to the nucleus after GJ inhibition. Adherent culture is usually more suitable for the stable expansion of cells than is a suspension culture. GJ inhibition is suggested to be a simple method to up-regulate pluripotency in an adherent culture that involves a Cx43-YAP axis in pluripotent stem cells, such as Muse cells.

Repeated anaphylactic reaction after walking following an intraarticular injection of diclofenac etalhyaluronate sodium during a 3-day period.

BACKGROUND: There has been no English report of repeated anaphylactic reaction after exercise-induced anaphylaxis due to a single intraarticular injection of diclofenac etalhyaluronate sodium. CASE PRESENTATION: A 60-year-old woman felt dyspnea, generalized itching, and urticaria following hypotension a few minutes after receiving an intraarticular injection of diclofenac etalhyaluronate sodium for the first time. She immediately received intramuscular adrenaline administration and her symptoms subsided. However, she received intermittent injections of adrenaline three times for repeated anaphylactic reactions after walking over a 3-day period, in addition to complication with Kounis syndrome. She was discharged on foot on day 9 without sequelae. CONCLUSION: Physicians should have patients who receive intraarticular injection of diclofenac etalhyaluronate sodium walk for a short period and evaluate their status.

Survey of trauma patients injured by falling or flying objects in Japan based on the Japan Trauma Data Bank.

PURPOSE: We retrospectively investigated patients injured by falling/flying objects using the Japan Trauma Data Bank (JTDB). METHODS: The study collected information of the JTEB from January 2004 to May 2019. The subjects were divided into two groups: the unexpected accident (UA) group included cases in which the patient was injured by an unexpected accident; the labor accident (LA) group included cases in which the patient was injured at work. RESULTS: A total of 1997 patients were enrolled as subjects (UA group, n = 383; LA group, n = 1134). In both groups, head injuries were the most frequent type of injury, followed by chest injuries. The median head abbreviated injury scale of the UA group was significantly higher than that of the LA group. In the UA group, the percentage of female patients, average age, and average TRISS value were significantly greater in comparison to the LA group. The frequency of emergency operations in the UA group was significantly lower in comparison to the LA group. The frequency of head injuries in the UA group was significantly greater than that in the LA group. The frequencies of upper extremity and lower extremity injuries in the UA group were significantly lower than those in the LA group. CONCLUSION: This is the first report to analyze trauma patients injured by falling/flying objects using the JTDB. Public health and emergency providers can use this information to anticipate the health-care needs after falling/flying object injuries.

Intravenous injection of human multilineage-differentiating stress-enduring cells alleviates mouse severe acute pancreatitis without immunosuppressants.

INTRODUCTION: We examined the effect of intravenously injected human multilineage-differentiating stress-enduring (Muse) cells, non-tumorigenic endogenous reparative stem cells already used in clinical trials, on a severe acute pancreatitis (SAP) mouse model without immunosuppressants. METHODS: Human Muse cells (1.0 × 105 cells) collected from mesenchymal stem cells (MSCs) as SSEA-3(+) were injected into a C57BL/6 mouse model via the jugular vein 6 h after SAP-induction with taurocholate. The control group received saline or the same number of SSEA-3(-)-non-Muse MSCs. RESULTS: Edematous parameters, F4/80(+) macrophage infiltration and terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity was the lowest and the number of proliferating endogenous pancreatic progenitors (CK18(+)/Ki67(+) cells) the highest in the Muse group among the three groups, with statistical significance, at 72 h. An enzyme-linked immunosorbent assay and quantitative polymerase chain reaction demonstrated that in vitro production of VEGF, HGF, IGF-1, and MMP-2, which are relevant to tissue protection, anti-inflammation, and anti-fibrosis, were higher in Muse cells than in non-Muse MSCs, particularly when cells were cultured in SAP mouse serum. Consistently, the pancreas of animals in the Muse group contained higher amounts of those factors according to Western blotting at 18 h than that in the non-Muse MSCs and control groups. CONCLUSIONS: Intravenous injection of human Muse cells was suggested to be effective for attenuating edema, inflammation and apoptosis in the acute phase of SAP.

Significance of medical intervention for non-traumatic hemorrhagic cardiac tamponade.

BACKGROUND: The outcomes of patients with cardiac arrest induced by non-traumatic hemorrhagic cardiac tamponade are poor. PURPOSE: We retrospectively investigated the significance of medical intervention with pericardiocentesis and/or pericardiotomy for non-traumatic hemorrhagic cardiac tamponade. METHODS: From January 2013 to April 2021, we retrospectively reviewed the medical charts of all patients with cardiac arrest in a prehospital setting or emergency room due to cardiac tamponade confirmed by an ultrasound examination with or without an invasive procedure (pericardiocentesis and/or pericardiotomy) and computed tomography findings, including those obtained at autopsy imaging. The subjects were divided into two groups: the Intervention (+) group, which included subjects who underwent pericardiocentesis or pericardiotomy, and the Intervention (-) group, which included subjects who did not undergo pericardiocentesis or pericardiotomy. Variables were then compared between the two groups. RESULTS: There were 68 patients with non-traumatic cardiac tamponade. All three survival cases had witnessed collapse, and the initial rhythm was pulseless electrical activity (PEA).There were no statistically significant differences in the sex, age, means of transportation, bystander chest compression, electric shock, or adrenalineor FDP levels between the two groups.However, the number with witnessed collapse, PEA, rupture of the heart;the ratio of obtaining return of spontaneous circulation; and the survival ratio were significantly greater in the Intervention (+) group than in the Intervention (-) group. CONCLUSION: Based on the results of preliminary study, we hypothesized that invasive medical intervention for patients with cardiac arrest induced by non-traumatic hemorrhagic cardiac tamponade might be useful for obtaining return of spontaneous circulation and a survival outcome, especially for patients with witnessed collapse with PEA as the initial rhythm.

The utility of physician-staffed helicopters for managing individuals who experience severe isolated head trauma.

Objective: The authors retrospectively investigated prognostic factors for severe isolated head trauma in patients evacuated by a physician-staffed helicopter emergency medical service (HEMS) or ground ambulance using data from the Japan Trauma Data Bank (JTDB). Patients and Methods: This study was a retrospective analysis of data housed in the JTDB database. The study period was from January 2004 to May 2019. Subjects were divided into two groups according to the method of transportation: helicopter (i.e., HEMS), which included patients transported by a physician-staffed helicopter; and ambulance, which included patients transported by ground ambulance. Results: A total of 41,358 patients were enrolled in the study, including 2,029 in the helicopter group and 39,329 in the ambulance group. The ratio of males, median head Abbreviated Injury Scale and Injury Severity Scale (ISS) scores were significantly greater in the helicopter group than in the ambulance group, while the average age, median Glasgow Coma Scale, average Revised Trauma Score (RTS), and survival rate were significantly lower in the helicopter group than in the ambulance group. Of the variables that demonstrated statistical significance in the univariate analysis and classification of transportation and included in the multivariate analysis, the following were identified as significant predictors of survival outcomes: younger age, lower ISS, female sex, and greater RTS. HEMS was not a significant predictor of survival. Conclusion: The present study revealed no effect of HEMS transport on the outcomes of patients who experienced severe isolated head trauma compared with ground ambulance transportation. Further prospective studies, including an analysis of the operation time or distance traveled by the HEMS and the functional outcome(s) of patients with severe head injury transported by HEMS, are warranted.

Transient Trabecular Formation in the Bladder and Delayed Free Air due to Traumatic Intraperitoneal Bladder Rupture.

An H-section steel bar that had been set against the wall fell and hit the abdomen and then both legs of a 33-year-old Chinese man. As his vital signs were stable and his chief complaint was leg pain, he was transferred to a local medical facility. After the confirmation of gross hematuria by an indwelling a bladder catheter there, he was transported to our hospital. On arrival, his vital signs were stable. His main complaint was foot pain. He had a scabbing injury at the scrotum and bilateral foot joint deformity. Whole-body computed tomography (CT) from head to toe revealed trabecular formation in the bladder and slight fluid collection in the rectovesical pouch, as well as bilateral fracture-dislocations at the ankles. The urinary tract injury and the fluid collection in the rectovesical pouch were managed conservatively, and the lower limbs were treated tentatively. Follow-up CT on day 3 revealed multiple free air pockets in the intra-abdominal cavity, which was considered to indicate perforation of the duodenal ulcer and treated conservatively. However, he showed abdominal pain on day 7, and repeated CT revealed increased fluid in the intra-abdominal cavity. Urgent laparoscopy showed intact bowels and perforation of the bladder that was closed by suturing. He ultimately obtained a survival outcome. This is the first case of transient trabecular formation in the bladder and delayed free air due to traumatic intraperitoneal bladder rupture. This unique case adds another radiological finding to the list of documented etiologies of traumatic bladder perforation.

Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases.

Muse cells are non-tumorigenic endogenous reparative pluripotent cells with high therapeutic potential. They are identified as cells positive for the pluripotent surface marker SSEA-3 in the bone marrow, peripheral blood, and connective tissue. Muse cells also express other pluripotent stem cell markers, are able to differentiate into cells representative of all three germ layers, self-renew from a single cell, and are stress tolerant. They express receptors for sphingosine-1-phosphate (S1P), which is actively produced by damaged cells, allowing circulating cells to selectively home to damaged tissue. Muse cells spontaneously differentiate on-site into multiple tissue-constituent cells with few errors and replace damaged/apoptotic cells with functional cells, thereby contributing to tissue repair. Intravenous injection of exogenous Muse cells to increase the number of circulating Muse cells enhances their reparative activity. Muse cells also have a specific immunomodulatory system, represented by HLA-G expression, allowing them to be directly administered without HLA-matching or immunosuppressant treatment. Owing to these unique characteristics, clinical trials using intravenously administered donor-Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, and amyotrophic lateral sclerosis. Muse cells have the potential to break through the limitations of current cell therapies for neurologic diseases, including amyotrophic lateral sclerosis. Muse cells provide a new therapeutic strategy that requires no HLA-matching or immunosuppressant treatment for administering donor-derived cells, no gene introduction or differentiation induction for cell preparation, and no surgery for delivering the cells to patients.

Isolation and characterization of bone marrow-derived mesenchymal stem cells in Xenopus laevis.

Mesenchymal stem cells (MSCs) are multipotent cells that exist in mesenchymal tissues such as bone marrow and are able to differentiate into osteocytes, chondrocytes, and adipocytes. MSCs are generally collected as adherent cells on a plastic dish, and are positive for markers such as CD44, CD73, CD90, CD105 and CD166, and negative for CD11b, CD14, CD19, CD31, CD34, CD45, CD79a and HLA-DR. MSCs have been established from many kinds of mammals, but MSCs from amphibians have not yet been reported. We cultured adherent cells from the bone marrow of Xenopus laevis by modifying the protocol for culturing mammalian MSCs. The morphology of these cells was similar to that of mammalian MSCs. The amphibian MSCs were positive for cd44, cd73, cd90 and cd166, and negative for cd11b, cd14, cd19, cd31, cd34, cd45, cd79a and hla-dra. Moreover, they could be induced to differentiate into osteocyte-, chondrocyte-, and adipocyte-lineage cells by cytokine induction systems that were similar to those used for mammalian MSC differentiation. Thus, they are considered to be similar to mammalian MSCs. Unlike mammals, amphibians have high regenerative capacity. The findings from the present study will allow for future research to reveal how Xenopus MSCs are involved in the amphibian regenerative capacity and to elucidate the differences in the regenerative capacity between mammals and amphibians.

Experience Using a Forehead Continuous Deep Temperature Monitoring System During Air Evacuation.

OBJECTIVE: The present study describes the utility of a forehead continuous deep temperature monitoring system by the staff members of a doctor helicopter (DH). METHODS: A questionnaire survey was performed for all flight doctors who had used this system during transportation by the DH to assess its merits and demerits. RESULTS: The major benefits of this system were its easy usability, disposable nature, low labor cost, continuous demonstration of the deep temperature in a prehospital setting, and low invasiveness. However, drawbacks of this system include its cost; need for a power supply; need for a few minutes for calibration to obtain stable results of temperature, making it impossible to verify the effects of intervention for body temperature during a short flight; and lack of a detachable measuring pad for the forehead when a patient has an injury on the face or head and hyperhidrosis. In addition, the system's attached cables may hamper medical interventions. CONCLUSION: We reported the experience of DH staff using a forehead continuous deep temperature monitoring system in the prehospital setting. Further studies will be required to determine the indications for using such a system in the prehospital setting.