Published papers

BACKGROUND The benefits of physician-staffed emergency medical services (EMS) for trauma patients remain unclear because of the conflicting results on survival. Some studies suggested potential delays in definitive hemostasis due to prolonged prehospital stay when physicians are dispatched to the scene. We examined hypotensive trauma patients who were transported by ambulance, with the hypothesis that physician-staffed ambulances would be associated with increased in-hospital mortality, compared with EMS personnel-staffed ambulances. METHODS A retrospective cohort study that included hypotensive trauma patients (systolic blood pressure ≤ 90 mm Hg at the scene) transported by ambulance was conducted using the Japan Trauma Data Bank (2004-2019). Physician-staffed ambulances are capable of resuscitative procedures, such as thoracotomy and surgical airway management, while EMS personnel-staffed ambulances could only provide advanced life support. In-hospital mortality and prehospital time until the hospital arrival were compared between patients who were classified based on the type of ambulance. Inverse probability weighting was conducted to adjust baseline characteristics including age, sex, comorbidities, mechanism of injury, vital signs at the scene, injury severity, and ambulance dispatch time. RESULTS Among 14,652 patients eligible for the study, 738 were transported by a physician-staffed ambulance. In-hospital mortality was higher in the physician-staffed ambulance than in the EMS personnel-staffed ambulance (201/699 [28.8%] vs. 2287/13,090 [17.5%]; odds ratio, 1.90 [1.61-2.26]; adjusted odds ratio, 1.22 [1.14-1.30]; p < 0.01), and the physician-staffed ambulance showed longer prehospital time (50 [36-66] vs. 37 [29-48] min, difference = 12 [11-12] min, p < 0.01). Such potential harm of the physician-staffed ambulance was only observed among patients who arrived at the hospital with persistent hypotension (systolic blood pressure < 90 mm Hg on hospital arrival) in subgroup analyses. CONCLUSION Physician-staffed ambulances were associated with prolonged prehospital stay and increased in-hospital mortality among hypotensive trauma patients compared with EMS personnel-staffed ambulance. LEVEL OF EVIDENCE Therapeutic, level IV.

Objective: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a less-invasive method for temporary hemostasis compared with cross-clamping the aorta through resuscitative thoracotomy (RT). Although the survival benefits of REBOA remained unclear, pathophysiological benefits were identified in patients with traumatic out-of-hospital cardiac arrest (t-OHCA). We examined the clinical outcomes of t-OHCA with the hypothesis that REBOA would be associated with higher survival to discharge compared with RT. Methods: A retrospective cohort study was conducted using the Japan Trauma Data Bank (2004-2019). Adult patients with t-OHCA who had arrived without a palpable pulse and undergone aortic occlusion were included. Patients were divided into REBOA or RT groups, and propensity scores were developed using age, mechanism of injury, presence of signs of life, presence of severe head and/or chest injury, Injury Severity Score, and transportation time. Inverse probability weighting by propensity scores was performed to compare survival to discharge between the 2 groups. Results: Among 13,247 patients with t-OHCA, 1483 were included in this study. A total of 144 (9.7%) patients were treated with REBOA, and 5 of 144 (3.5%) in the REBOA group and 10 of 1339 (0.7%) in the RT group survived to discharge. The use of REBOA was significantly associated with increased survival to discharge (odds ratio, 4.78; 95% confidence interval, 1.61-14.19), which was confirmed by inverse probability weighting (adjusted odds ratio, 3.73; 95% confidence interval, 1.90-7.32). Conclusions: REBOA for t-OHCA was associated with higher survival to discharge. These results should be validated by further research.

The clinical course of coronavirus disease 2019 (COVID-19) varies from mild to critical. We retrospectively examined whether clinical and laboratory findings on admission could predict COVID-19 prognosis. Among various factors associated with COVID-19 severity, our results indicated that the real-time reverse transcription-polymerase chain reaction (RT-PCR) threshold cycle (Ct) values for severe acute respiratory syndrome coronavirus 2 were the most useful predictor of COVID-19 prognosis.

Background: Burns resulting from assaults account for considerable morbidity and mortality among patients with burn injuries around the world. However, it is still unclear whether unfavorable clinical outcomes are associated primarily with the severity of the injuries. To elucidate the direct relationship between burns resulting from assaults and mortality and/or length of hospital stays, we performed this study with the hypothesis that burns from assault would be independently associated with fewer hospital-free days than would burns from other causes, regardless of the severity of burn injuries. Methods: We conducted a retrospective cohort study, using a city-wide burn registry (1996-2017) accounting for 14 burn centers in Tokyo, Japan. Patients who arrived within 24 hours after injury were included, and those with self-inflicted burn injuries were excluded. Patients were divided into two groups according to mechanism of burns (assault vs. accident), and the number of hospital-free days until day 30 after injury (a composite of in-hospital death and hospital length of stay) was compared between the groups. To estimate the probability that an injury would be classified as an assault, we calculated propensity scores, using multivariate logistic regression analyses adjusted for known outcome predictors. We also performed an inverse probability weighting (IPW) analysis to compare adjusted numbers of hospital-free days. Results: Of 7419 patients in the registry with burn injuries during the study period, 5119 patients were included in this study. Of these, 113 (2.2%) were injured as a result of assault; they had significantly fewer hospital-free days than did those with burns caused by accident (18 [27] vs. 24 [20] days; coefficient = [Formula: see text]3.4 [[Formula: see text]5.5 to [Formula: see text]1.3] days; p = 0.001). IPW analyses similarly revealed the independent association between assault burn injury and fewer hospital-free days (adjusted coefficient = [Formula: see text]0.6 [[Formula: see text]1.0 to [Formula: see text]0.1] days; p = 0.009). Conclusions: Burn from assault was independently associated with fewer hospital-free days, regardless of the severity of burn injuries. The pathophysiological mechanism underlying the relationship should be further studied in a prospective observational study.

BACKGROUND: Hydrogen gas (H2) inhalation during hemorrhage stabilizes post-resuscitation hemodynamics, improving short-term survival in a rat hemorrhagic shock and resuscitation (HS/R) model. However, the underlying molecular mechanism of H2 in HS/R is unclear. Endothelial glycocalyx (EG) damage causes hemodynamic failure associated with HS/R. In this study, we tested the hypothesis that H2 alleviates oxidative stress by suppressing xanthine oxidoreductase (XOR) and/or preventing tumor necrosis factor-alfa (TNF-α)-mediated syndecan-1 shedding during EG damage. METHODS: HS/R was induced in rats by reducing mean arterial pressure (MAP) to 35 mm Hg for 60 min followed by resuscitation. Rats inhaled oxygen or H2 + oxygen after achieving shock either in the presence or absence of an XOR inhibitor (XOR-I) for both the groups. In a second test, rats received oxygen alone or antitumor necrosis factor (TNF)-α monoclonal antibody with oxygen or H2. Two hours after resuscitation, XOR activity, purine metabolites, cytokines, syndecan-1 were measured and survival rates were assessed 6 h after resuscitation. RESULTS: H2 and XOR-I both suppressed MAP reduction and improved survival rates. H2 did not affect XOR activity and the therapeutic effects of XOR-I and H2 were additive. H2 suppressed plasma TNF-α and syndecan-1 expression; however, no additional H2 therapeutic effect was observed in the presence of anti-TNF-α monoclonal antibody. CONCLUSIONS: H2 inhalation after shock stabilized hemodynamics and improved survival rates in an HS/R model independent of XOR. The therapeutic action of H2 was partially mediated by inhibition of TNF-α-dependent syndecan-1 shedding.

BACKGROUND: Patients with mesenteric ischemia frequently suffer from bowel necrosis even after revascularization. Hydrogen gas has showed promising effects for ischemia-reperfusion injury by reducing reactive oxygen species in various animal and clinical studies. We examined intestinal tissue injury by ischemia and reperfusion under continuous initiation of 3% hydrogen gas. AIM: To clarify the treatment effects and target cells of hydrogen gas for mesenteric ischemia. METHODS: Three rat groups underwent 60-min mesenteric artery occlusion (ischemia), 60-min reperfusion following 60-min occlusion (reperfusion), or ischemia-reperfusion with the same duration under continuous 3% hydrogen gas inhalation (hydrogen). The distal ileum was harvested. Immunofluorescence staining with caspase-3 and leucine-rich repeat-containing G-protein-coupled 5 (LGR5), a specific marker of intestinal stem cell, was conducted to evaluate the injury location and cell types protected by hydrogen. mRNA expressions of LGR5, olfactomedin 4 (OLFM4), hairy and enhancer of split 1, Jagged 2, and Neurogenic locus notch homolog protein 1 were measured by quantitative polymerase chain reaction. Tissue oxidative stress was analyzed with immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG). Systemic oxidative stress was evaluated by plasma 8-OHdG. RESULTS: Ischemia damaged the epithelial layer at the tip of the villi, whereas reperfusion induced extensive apoptosis of the cells at the crypt base, which were identified as intestinal stem cells with double immunofluorescence stain. Hydrogen mitigated such apoptosis at the crypt base, and the LGR5 expression of the tissues was higher in the hydrogen group than in the reperfusion group. OLFM4 was also relatively higher in the hydrogen group, whereas other measured RNAs were comparable between the groups. 8-OHdG concentration was high in the reperfusion group, which was reduced by hydrogen, particularly at the crypt base. Serum 8-OHdG concentrations were relatively higher in both reperfusion and hydrogen groups without significance. CONCLUSION: This study demonstrated that hydrogen gas inhalation preserves intestinal stem cells and mitigates oxidative stress caused by mesenteric ischemia and reperfusion.

Objective To investigate the similarities and differences between Coronavirus disease 2019 (COVID-19) and autoimmune and autoinflammatory rheumatic diseases characterised by hyperferritinaemia, such as antimelanoma differentiation-associated protein 5 (MDA5) autoantibody-positive dermatomyositis and adult Still’s disease. Methods We reviewed consecutive, newly diagnosed, untreated patients with COVID-19, anti-MDA5 dermatomyositis, or adult Still’s disease. We compared their clinical, laboratory, and radiological characteristics, including the prevalence of macrophage activation syndrome and lung involvement in each disease. Results The numbers of patients with COVID-19, anti-MDA5 dermatomyositis, and adult-onset Still’s disease with hyperferritinaemia (serum ferritin ≥500ng/dL) who were included for main analysis were 22, 14, and 59, respectively. COVID-19 and adult Still’s disease both featured hyperinflammatory status, such as high fever and elevated serum C-reactive protein, whereas COVID-19 and anti-MDA5 dermatomyositis both presented with severe interstitial lung disease and hypoxaemia. While two-thirds of the patients in each group met the criteria for macrophage-activated syndrome that is used in systemic juvenile idiopathic arthritis, the HScore, an indicator of haemophagocytic lymphohistiocytosis, was low in anti-MDA5 dermatomyositis and COVID-19 even in severe or critical cases. The findings of chest computed tomography were similar between COVID-19 and anti-MDA5 dermatomyositis. Conclusion COVID-19 shared clinical features with rheumatic diseases characterised by hyperferritinaemia, including anti-MDA5 dermatomyositis and adult Still’s disease. These findings should be investigated further in order to shed light on the pathogenesis of not only COVID-19 but also the aforementioned rheumatic diseases.

Abstract At mass-gathering events of the Olympic and Paralympic Games, a well-organized, on-site medical system is essential. This study evaluated the vulnerabilities of the prehospital medical system of the TOKYO 2020 Olympic and Paralympic Games (TOKYO2020) to propose corrections that can be generalized to other mass gatherings. The healthcare failure mode and effect analysis (HFMEA) was adopted to analyze vulnerabilities of the on-site medical system proposed by the organizing committee of TOKYO2020. Processes from detecting a patient on the scene to completing transport to a hospital were analyzed. Ten processes with 47 sub-processes and 122 possible failure modes were identified. HFMEA revealed 9 failure modes as vulnerabilities: misidentification of patient, delayed immediate care at the scene, misjudgment of disposition from the on-site medical suite, and inappropriate care during transportation to hospital. Proposed corrections included surveillance to decrease blind spots, first aid brochures for spectators, and uniform protocol for health care providers at the scene. The on-site medical system amended by HFMEA seemed to work appropriately in TOKYO2020.

BACKGROUND: Strategies to predict delayed airway obstruction in patients with inhalation injury have not been extensively studied. This study aimed to develop a novel scale, predicting the need for Delayed Intubation after inhalation injury (PDI) score. METHODS: We retrospectively identified patients with inhalation injury at four tertiary care centers in Japan between 2012 and 2018. We included patients aged 15 or older and excluded those intubated within 30 min after hospital arrival. Predictors for delayed intubation were identified with univariate analyses and scored on the basis of odds ratios. The PDI score was evaluated with the area under the receiver operating characteristic (AUROC) curve and compared with other scaling systems for burn injuries. RESULTS: Data from 158 patients were analyzed; of these patients, 18 (11.4%) were intubated during the delayed phase. Signs of respiratory distress, facial burn, and pharyngolaryngeal swelling observed on laryngoscopy, were identified as predictors for delayed intubation. The discriminatory power of the PDI (AUROC curve = 0.90; 95% confidence interval, 0.83 to 0.97; p < 0.01) was higher than that of the other scaling systems. CONCLUSIONS: We developed a novel scale for predicting delayed intubation in inhalation injury. The score should be further validated with other population.