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Hydrogen has therapeutic and preventive effects against various diseases. Although animal and clinical studies have reported promising results, hydrogen distribution in organs after administration remains unclear. Herein, the sequential changes in hydrogen concentration in tissues over time were monitored using a highly sensitive glass microsensor and continuous inhalation of 3% hydrogen gas. The hydrogen concentration was measured in the brain, liver, kidney, mesentery fat and thigh muscle of rats. The maximum concentration, time to saturation, and other measurements representing the dynamics of distribution were obtained from the concentration curves, and the results obtained for different organs were compared. The time to saturation was significantly longer (20.2 vs 6.3–9.4 min. P  = 0.004 in all cases) and increased more gradually in muscle than in the other organs. The maximum concentration was the highest in liver and the lowest in the kidney (29.0 ± 2.6 vs 18.0 ± 2.2 μmol/L; P  = 0.03 in all cases). The concentration varied significantly depending on the organ ( P  = 0.03). These results provide the fundamentals for elucidating the mechanisms underlying the in vivo favourable effects of hydrogen gas in mammalian systems.

Platelet activation after muscle trauma promotes extracellular trap release by macrophages and acute kidney injury. Rhabdomyolysis is a serious syndrome caused by skeletal muscle injury and the subsequent release of breakdown products from damaged muscle cells into systemic circulation 1 . The muscle damage most often results from strenuous exercise, muscle hypoxia, medications, or drug abuse and can lead to life-threatening complications, such as acute kidney injury (AKI) 1 . Rhabdomyolysis and the AKI complication can also occur during crush syndrome, an emergency condition that commonly occurs in victims of natural disasters, such as earthquakes, and man-made disasters, such as wars and terrorism 2 . Myoglobin released from damaged muscle is believed to trigger renal dysfunction in this form of AKI. Recently, macrophages were implicated in the disease pathogenesis of rhabdomyolysis-induced AKI 3 , 4 , but the precise molecular mechanism remains unclear. In the present study, we show that macrophages released extracellular traps (ETs) comprising DNA fibers and granule proteins in a mouse model of rhabdomyolysis. Heme-activated platelets released from necrotic muscle cells during rhabdomyolysis enhanced the production of macrophage extracellular traps (METs) through increasing intracellular reactive oxygen species generation and histone citrullination. Here we report, for the first time to our knowledge, this unanticipated role for METs and platelets as a sensor of myoglobin-derived heme in rhabdomyolysis-induced AKI. This previously unknown mechanism might be targeted for treatment of the disease. Finally, we found a new therapeutic tool for prevention of AKI after rhabdomyolysis, which might rescue some sufferers of this pathology.

Emergency department thoracotomy (EDT) was incorporated into traumatic out-of-hospital cardiac arrest (t-OHCA) resuscitation. Although current guidelines recommend EDT with survival predictors, futility following EDT has been demonstrated and the potential risks have not been thoroughly investigated. This study aimed to elucidate the benefits and harms of EDT for persistent cardiac arrest following injury until hospital arrival. This retrospective cohort study used a nationwide trauma registry (2019–2021) and included adult patients with t-OHCA both at the scene and on hospital arrival. Survival to discharge, hemostatic procedure frequency, and transfusion amount were compared between patients treated with and without EDT. Inverse probability weighting using a propensity score was conducted to adjust age, sex, comorbidities, mechanism of injury, prehospital resuscitative procedure, prehospital physician presence, presence of signs of life, degree of thoracic injury, transportation time, and institutional characteristics. Among 1289 patients, 374 underwent EDT. The longest transportation time for survivors was 8 and 23 min in patients with and without EDT, respectively. EDT was associated with lower survival to discharge (4/374 [1.1%] vs. 22/915 [2.4%]; adjusted odds ratio [OR], 0.43 [95% CI 0.22–0.84]; p  = 0.011), although patients with EDT underwent more frequent hemostatic surgeries (46.0% vs. 5.0%; adjusted OR, 16.39 [95% CI 12.50–21.74]) and received a higher amount of transfusion. Subgroup analyses revealed no association between EDT and lower survival in patients with severe chest injuries (1.0% vs. 1.4%; adjusted OR, 0.72 [95% CI 0.28–1.84]). EDT was associated with lower survival till discharge in trauma patients with persistent cardiac arrests after adjusting for various patient backgrounds, including known indications for EDT. The idea that EDT is the last resort for t-OHCA should be reconsidered and EDT indications need to be deliberately determined. Trial registration This study is retrospectively registered at University Hospital Medical Information Network (UMIN ID: UMIN000050840).

Patient with acute coronary syndrome benefits from early revascularization. However, methods for the selection of patients who require urgent revascularization from a variety of patients visiting the emergency room with chest symptoms is not fully established. Electrocardiogram is an easy and rapid procedure, but may contain crucial information not recognized even by well-trained physicians. To make a prediction model for the needs for urgent revascularization from 12-lead electrocardiogram recorded in the emergency room. We developed an artificial intelligence model enabling the detection of hidden information from a 12-lead electrocardiogram recorded in the emergency room. Electrocardiograms obtained from consecutive patients visiting the emergency room at Keio University Hospital from January 2012 to April 2018 with chest discomfort was collected. These data were splitted into validation and derivation dataset with no duplication in each dataset. The artificial intelligence model was constructed to select patients who require urgent revascularization within 48 hours. The model was trained with the derivation dataset and tested using the validation dataset. Of the consecutive 39,619 patients visiting the emergency room with chest discomfort, 362 underwent urgent revascularization. Of them, 249 were included in the derivation dataset and the remaining 113 were included in validation dataset. For the control, 300 were randomly selected as derivation dataset and another 130 patients were randomly selected for validation dataset from the 39,317 who did not undergo urgent revascularization. On validation, our artificial intelligence model had predictive value of the c-statistics 0.88 (95% CI 0.84-0.93) for detecting patients who required urgent revascularization. Our artificial intelligence model provides information to select patients who need urgent revascularization from only 12-leads electrocardiogram in those visiting the emergency room with chest discomfort.

Background The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. Methods This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. Results In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. Conclusion A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival.

Background Supraphysiologic oxygen administration causes unfavorable clinical outcomes in various diseases, including traumatic brain injury, post–cardiac arrest syndrome, and acute lung injury. Accidental hypothermia is a critical illness that reduces oxygen demands, and excessive oxygen is likely to emerge. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with accidental hypothermia. Methods A post-hoc analysis of a nationwide multicenter prospective observational study (ICE-CRASH study) on patients with accidental hypothermia admitted in 2019–2022 was conducted. Adult patients without cardiac arrest whose core body temperature was < 32 °C and whose arterial partial pressure of oxygen (PaO 2 ) was measured at the emergency department were included. Hyperoxia was defined as a PaO 2 level of 300 mmHg or higher, and 28-day mortality was compared between patients with and without hyperoxia before rewarming. Inverse probability weighting (IPW) analyses with propensity scores were performed to adjust patient demographics, comorbidities, etiology and severity of hypothermia, hemodynamic status and laboratories on arrival, and institution characteristics. Subgroup analyses were conducted according to age, chronic cardiopulmonary diseases, hemodynamic instability, and severity of hypothermia. Results Of the 338 patients who were eligible for the study, 65 had hyperoxia before rewarming. Patients with hyperoxia had a higher 28-day mortality rate than those without (25 (39.1%) vs. 51 (19.5%); odds ratio (OR) 2.65 (95% confidence interval 1.47–4.78); p  < 0.001). IPW analyses with propensity scores revealed similar results (adjusted OR 1.65 (1.14–2.38); p  = 0.008). Subgroup analyses showed that hyperoxia was harmful in the elderly and those with cardiopulmonary diseases and severe hypothermia below 28 °C, whereas hyperoxia exposure had no effect on mortality in patients with hemodynamic instability on hospital arrival. Conclusions Hyperoxia with PaO 2 levels of 300 mmHg or higher before initiating rewarming was associated with increased 28-day mortality in patients with accidental hypothermia. The amount of oxygen to administer to patients with accidental hypothermia should be carefully determined. Trial Registration : The ICE-CRASH study was registered at the University Hospital Medical Information Network Clinical Trial Registry on April 1, 2019 (UMIN-CTR ID, UMIN000036132).

A recent clinical study demonstrated that haemodialysis with a dialysate containing hydrogen (H 2 ) improves blood pressure control in end-stage kidney disease. Herein, we examined whether H 2 has a salutary effect on hypertension in animal models. We subjected 5/6 nephrectomised rats to inhalation of either H 2 (1.3% H 2  + 21% O 2  + 77.7% N 2 ) or control (21% O 2  + 79% N 2 ) gas mixture for 1 h per day. H 2 significantly suppressed increases in blood pressure after 5/6 nephrectomy. The anti-hypertensive effect of H 2 was also confirmed in rats in a stable hypertensive state 3 weeks after nephrectomy. To examine the detailed effects of H 2 on hypertension, we used an implanted telemetry system to continuously monitor blood pressure. H 2 exerted an anti-hypertensive effect not only during daytime rest, but also during night-time activities. Spectral analysis of blood pressure variability revealed that H 2 improved autonomic imbalance, namely by suppressing the overly active sympathetic nervous system and augmenting parasympathetic nervous system activity; these effects co-occurred with the blood pressure-lowering effect. In conclusion, 1-h daily exposure to H 2 exerts an anti-hypertensive effect in an animal model of hypertension.

Given that there are still considerable number of facilities which lack surgical specialists round the clock across the world, the ability to estimate the requirement for emergency surgery in victims of motor vehicle crashes (MVCs) can ensure appropriate resource allocation. In this study, a surgical intervention in victims of MVC (SIM) score was developed and validated, using independent patient cohorts. We retrospectively identified MVC victims in a nationwide trauma registry (2004-2016). Adults ≥ 15 years who presented with palpable pulse were included. Patients with missing data on the type/date of surgery were excluded. Patient were allocated to development or validation cohorts based on the date of injury. After missing values were imputed, predictors of the need for emergency thoracotomy and/or laparotomy were identified with multivariate logistic regression, and scores were then assigned using odds ratios. The SIM score was validated with area under the receiver operating characteristic curve (AUROC) and calibration plots of SIM score-derived probability and observed rates of emergency surgery. We assigned 13,328 and 12,348 patients to the development and validation cohorts, respectively. Age, motor vehicle collision and vital signs on hospital arrival were identified as independent predictors for emergency thoracotomy and/or laparotomy, and SIM score was developed as 0-9 scales. The score has a good discriminatory power (AUROC = 0.79; 95% confidence interval = 0.77-0.81), and both estimated and observed rates of emergency surgery increased stepwise from 1% at a score ≤ 1 to almost 40% at a score ≥ 8 with linear calibration plots. The SIM score was developed and validated to accurately estimate the need for emergent thoracotomy and/or laparotomy in MVC victims.

Background The discussion is ongoing about appropriate indications for laparoscopic surgery in trauma patients. As timing and risks of conversion to laparotomy remain unclear, we aimed to elucidate characteristics of and risks for conversion following laparoscopic surgery, using a nationwide database. Methods A retrospective observational study was conducted, using Japanese Trauma Data Bank (2004–2018). We included adult trauma patients who underwent laparoscopic surgery as an initial surgical intervention. Conversion to laparotomy was defined as laparotomy at the initial surgery. Patient demographics, mechanism and severity of injury, injured organs, timing of surgery, and clinical outcomes were compared between patients with and without conversion. Risks for conversion were analyzed focusing on indications for laparoscopic surgery, after adjusting patient and institution characteristics. Results Among 444 patients eligible for the study, 31 required conversions to laparotomy. The number of laparoscopic surgeries gradually increased over the study period (0.5–4.5% of trauma laparotomy), without changes in conversion rates (5–10%). Patients who underwent conversion had more severe abdominal injuries compared with those who did not (AIS 3 vs 2). While length of hospital stay and in-hospital mortality were comparable, abdominal complications were higher among patients with conversion (12.9 vs. 2.9%), particularly when laparoscopy was performed for peritonitis (OR, 22.08 [5.11–95.39]). A generalized estimating equation model adjusted patient background and identified hemoperitoneum and peritoneal penetration as risks for conversion (OR, 24.07 [7.35–78.75] and 8.26 [1.20– 56.75], respectively). Conclusions Trauma laparoscopy for hemoperitoneum and peritoneal penetration were associated with higher incidence of conversion to open laparotomy.

Crush syndrome, which frequently occurs in earthquake disasters, often leads to rhabdomyolysis induced acute kidney injury (RIAKI). Recent findings indicate that systemic inflammatory response syndrome (SIRS) exacerbates muscle collapse, contributing to RIAKI. The purpose of this study is to investigate the involvement of multiple site inflammation, including intraperitoneal, in crush syndrome. In a mouse model of RIAKI, elevated levels of inflammatory mediators such as TNFα, IL-6, myoglobin, and dsDNA were observed in serum and the peritoneal cavity, peaking earlier in the intraperitoneal cavity than in serum or urine. Our previously developed novel peptide inhibiting leukocyte extracellular traps was administered intraperitoneally and blocked all of these mediators in the intraperitoneal cavity and serum, ameliorating muscle damage and consequent RIAKI. Although further studies are needed to determine whether intraperitoneal inflammation associated with muscle collapse can lead to systemic inflammation, resulting in more severe and prolonged muscle damage and renal injury, early suppression of multiple site inflammation, including intraperitoneal, might be an effective therapeutic target.