Published papers

Males and females exhibit differences in proteome profiles associated with disease risk. However, sex-dimorphic protein quantitative trait loci (SD-pQTL) and their effects on sex differences in health disorders have not been thoroughly investigated. We conducted a sex-stratified, genome-wide association study on 2,922 proteins using data from 30,272 individuals of Caucasian ancestry from the UK Biobank and compared the estimated effects on protein levels of these variants in the men and women to identify SD-pQTLs. The identified SD-pQTLs were replicated using data from two Japanese cohorts (comprising 2,886 and 1,394 individuals, respectively), as well as from 1,990 Finnish, 630 South Asian, and 662 Black ancestry individuals. Sex-dimorphic pleiotropy and the causal relationship between protein levels and health disorders were assessed using the identified SD-pQTLs. We identified 113 SD-pQTLs associated with 65 proteins. Of the 113 SD-pQTLs, 52 were significant in both sexes, five were not significant in either sex, and 42 and 14 were significant only in males and females, respectively. Variant rs2270416 was significantly associated with the CDH15 protein in both sexes but showed opposite effect direction in men and women. Of the 113 SD-pQTLs identified, a total of 41 were replicated in a meta-analysis encompassing Japanese, South Asian, and Black ancestry individuals. SD-pQTLs for proteins APOE (rs157581) and SNAP25 (rs4420638) exhibited sex-dimorphic associations with dementia, indicating sex dimorphic pleiotropy in both proteins and health disorders. From sex-stratified Mendelian randomization using the SD-pQTLs, proteins NCAM1 and PZP showed significant causal relationship with dementia in males and females, respectively. The present study provides evidence of sex-dimorphic genetic architecture in protein-level regulation, elucidating the proteo-genetic architecture for sex differences in human variation.

Purpose: This study aimed to elucidate whether immediate angiography within 30 min is associated with lower in-hospital mortality compared with non-immediate angiography. Materials and Methods: We conducted a retrospective cohort study using a nationwide trauma databank (2019–2020). Adult trauma patients who underwent emergency angiography within 12 h after hospital arrival were included. Patients who underwent surgery before angiography were excluded. Immediate angiography was defined as one performed within 30 min after arrival (door-to-angio time ≤ 30 min). In-hospital mortality and non-operative management (NOM) failure were compared between patients with immediate and non-immediate angiography. Inverse probability weighting with propensity scores was conducted to adjust patient demographics, injury mechanism and severity, vital signs on hospital arrival, and resuscitative procedures. A restricted cubic spline curve was drawn to reveal survival benefits by door-to-angio time. Results: Among 1,455 patients eligible for this study, 92 underwent immediate angiography. Angiography ≤ 30 min was associated with decreased in-hospital mortality (5.0% vs 11.1%; adjusted odds ratio [OR], 0.42 [95% CI, 0.31–0.56]; p < 0.001), as well as lower frequency of NOM failure: thoracotomy and laparotomy after angiography (0.8% vs. 1.8%; OR, 0.44 [0.22–0.89] and 2.6% vs. 6.5%; OR, 0.38 [0.26–0.56], respectively). The spline curve showed a linear association between increasing mortality and prolonged door-to-angio time in the initial 100 min after arrival. Conclusion: In trauma patients, immediate angiography ≤ 30 min was associated with lower in-hospital mortality and fewer NOM failures. Level of Evidence: Level 3b, non randomized controlled cohort/follow up study. Graphical Abstract: (Figure presented.).

Background: Immediate whole-body CT (about 10 min after arrival) in an all-in-one resuscitation room equipped with CT has been found to be associated with shorter time to haemostasis and lower in-hospital mortality. The aim of this study was to elucidate the benefits of immediate whole-body CT after hospital arrival in patients with severe trauma with the hypothesis that immediate CT within 10 min is associated with lower in-hospital mortality. Method: This retrospective cohort study of patients with an injury severity score of more than 15 who underwent whole-body CT was conducted using the Japanese Trauma Databank (2019–2020). An immediate CT was conducted within 10 min after arrival. In-hospital mortality, frequency of subsequent surgery, and time to surgery were compared with immediate and non-immediate CT. Inverse probability weighting was conducted to adjust for patient backgrounds, including mechanism and severity of injury, prehospital treatment, vital signs, and institutional characteristics. Results: Among the 7832 patients included, 646 underwent immediate CT. Immediate CT was associated with lower in-hospital mortality (12.5 versus 15.7 per cent; adjusted OR 0.77 (95 per cent c.i. 0.69 to 0.84); P < 0.001) and fewer damage-control surgeries (OR 0.75 (95 per cent c.i. 0.65 to 0.87)). There was a 10 to 20 min difference in median time to craniotomy, laparotomy, and angiography. These benefits were observed regardless of haemodynamic instability on hospital arrival, while they were identified only in elderly patients with severe injury and altered consciousness. Conclusion: Immediate CT within 10 min after arrival was associated with decreased in-hospital mortality in severely injured trauma patients.

Background: The spread of coronavirus disease 2019 (COVID-19), which began in 2020, has had a major impact on healthcare systems. The spread of COVID-19 has been reported to have affected the readiness to treat patients with burns worldwide. However, the existing reports have evaluated burn care status within a limited time period during the pandemic, and no report clarifies the change in the impact of infection status on burn care from the beginning of the pandemic to the present. Methods: Japanese Society for Burn Injuries–accredited burn care facilities were surveyed using questionnaires on April 9–23, 2020; June 23–July 6, 2020; July 9–21, 2021; and January 21–31, 2022. Differences between groups were evaluated using Friedman's test or Bonferroni's multiple comparison test, as appropriate. Results: From the 103 facilities included in the study, we received 85, 55, 56, and 58 responses in the first, second, third, and fourth surveys, respectively. We could continuously observe 34 facilities. The rate of acceptance of patients with severe burns improved significantly over time (P < 0.05). However, in the second and third surveys, there was an increase in the number of respondents who did not accept patients with burns irrespective of COVID-19 status. Conclusions: The number of facilities treating patients with burns who have COVID-19 is increasing; however, COVID-19 care may negatively impact routine burn care. It is necessary to continuously examine medical resource allocation through methods such as information sharing by academic societies.

Objective: This study aimed to evaluate the impact of drain placement on the incidence of postoperative complications in patients undergoing gastrectomy. Background: The effectiveness of prophylactic abdominal drain placement in gastrectomy remains unclear. Nevertheless, they are still commonly used following gastrectomy. Methods: We conducted a retrospective cohort study using a nationwide inpatient database in Japan. Patients who underwent gastrectomy for gastric cancer between January 2014 and March 2022 were included. We applied overlap weighting based on propensity scores to adjust for baseline characteristics. The primary outcome was the incidence of intra-abdominal infections. Secondary outcomes included postoperative percutaneous drainage, in-hospital death, length of hospital stay, and total hospitalization costs. Results: A total of 217,750 patients met the inclusion criteria, and 196,660 (90.3%) received prophylactic abdominal drains. After overlap weighting, the drain group had a significantly lower incidence of intra-abdominal infections compared to the no-drain group (6.3% vs. 7.6%; 95% confidence interval [CI] − 1.7 to − 1.0). The prophylactic drains were also associated with reduced in-hospital postoperative mortality (0.6% vs. 0.8%; 95% CI − 0.3 to − 0.1). No significant differences were observed between the two groups in postoperative percutaneous drainage or hospital stay duration. Conclusion: This study suggests that prophylactic abdominal drainage was associated with a reduced incidence of intra-abdominal infections after gastrectomy without increasing hospitalization duration or medical costs.

Glycemic control strategies for sepsis have changed significantly over the last decade, but their impact on dysglycemia and its associated outcomes has been poorly understood. In addition, there is controversy regarding the detrimental effects of hyperglycemia in sepsis. To evaluate the incidence and risks of dysglycemia under current strategy, we conducted a preplanned subanalysis of the sepsis cohort in a prospective, multicenter FORECAST study. A total of 1,140 patients with severe sepsis, including 259 patients with pre-existing diabetes, were included. Median blood glucose levels were approximately 140mg/dL at 0 and 72h indicating that blood glucose was moderately controlled. The rate of initial and late hyperglycemia was 27.3% and 21.7%, respectively. The rate of early hypoglycemic episodes during the initial 24h was 13.2%. Glycemic control was accompanied by a higher percentage of initial and late hyperglycemia but not with early hypoglycemic episodes, suggesting that glycemic control was targeted at excess hyperglycemia. In nondiabetic patients, late hyperglycemia (hazard ratio, 95% confidence interval; P value: 1.816, 1.116-2.955, 0.016) and early hypoglycemic episodes (1.936, 1.180-3.175, 0.009) were positively associated with in-hospital mortality. Further subgroup analysis suggested that late hyperglycemia and early hypoglycemic episodes independently, and probably synergistically, affect the outcomes. In diabetic patients, however, these correlations were not observed. In conclusion, a significantly high incidence of dysglycemia was observed in our sepsis cohort under moderate glycemic control. Late hyperglycemia in addition to early hypoglycemia was associated with poor outcomes at least in nondiabetic patients. More sophisticated approaches are necessary to reduce the incidence of these serious complications.

Introduction: Open abdomen (OA) is a widely used technique for managing abdominal organ injury, abdominal compartment syndrome, and abdominal sepsis. While various methods have contributed to successful primary closure of the abdominal fascia after OA, some patients still develop enteroatmospheric fistulas that impede abdominal fascia closure. We report a case of successful epithelialization of the incision by sequential partial split-thickness skin grafting (STSG) in a patient who had failure in primary abdominal fascia closure due to enteroatmospheric fistulas after OA for incisional dehiscence and anastomotic leakage. Presentation of case: A 73-year-old male patient underwent pancreaticoduodenectomy for duodenal adenocarcinoma. The abdominal incision was then necrosed and dehisced due to anastomotic leakage on postoperative day (POD) 6, and multiple intra-abdominal lavages with OA were performed. On POD 15, the patient developed enteroatmospheric fistulas; thus, primary fascia closure was considered impossible. On PODs 72 and 106, STSG was conducted on the granulation tissue at the incisional wound, and complete epithelialization was achieved on POD 111. Discussion: Sequential partial STSG only needed basic surgical skills and standard devices for surgery. Conclusion: We reported the case with successful epithelialization of the incision by sequential partial STSG, in which primary abdominal fascia closure was failed due to enteroatmospheric fistulas after OA for incisional dehiscence and anastomotic leakage.

Introduction: Infection and mortality rates caused by the coronavirus infectious disease 2019 (COVID-19) pandemic were high. However, the influence of the COVID-19 pandemic on the clinical burden in medical facilities remains to be clarified in Japan. Materials and methods: This study used a questionnaire-based web survey to clarify how the COVID-19 pandemic affected infectious disease practice and infection control. The questionnaire was sent to healthcare professionals at nationwide medical facilities between January 13, 2023, and February 15, 2023. Results: Responses were obtained from 1784 healthcare professionals throughout Japan. Hospital management of COVID-19 patients was the responsibility of 96.5% of respondents. Furthermore, 75.1% had experienced nosocomial spread of COVID-19. Manuals and infection control measures for COVID-19 have been arranged in most facilities. In many facilities, the timing of an infected employee's return to work was determined in accordance with the isolation period for coronavirus-positive patients with symptoms established by the Ministry of Health, Labor and Welfare in Japan. Approximately 30% of respondents reported that caring for COVID-19 patients, including the use of personal protective equipment, was their most stressful job. Approximately 50% of the respondents reported an increase in overtime hours. Approximately 90% of facilities are now capable of performing COVID-19 testing onsite. Conclusion: Infection control for COVID-19 has been improved, and testing equipment for SARS-CoV-2 has been prepared. Patient care-related burdens and burdens caused by having to compensate for vacancies due to infected staff members have increased. In the future, a reduction in workload and role sharing should be considered.

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Purpose: The ability to accurately evaluate the severity of inhalation injury can help to optimize patient care. However, there is no accepted severity grading system, especially for inhalation injury. Methods: We screened a multicenter burn registry and included adult patients who required oxygen treatment or mechanical ventilation. After the patient data were divided into development and validation cohorts, missing values were replaced with multiple imputation. Twelve potential predictors were analyzed using multivariate logistic regression to identify prognostic variables for in-hospital mortality and scores were assigned to each predictor based on odds ratios to develop the Modified Abbreviated Burn Severity Index, mABSI. The mABSI was validated using c-statistics and calibration curves. Results: We randomly assigned 1377 and 919 patients to the development and validation cohorts, respectively. Age, self-inflicted injury, cutaneous burn area, and mechanical ventilation requirement were identified as independent predictors, and the mABSI (1–17 scale) was, thus, developed. The mABSI has a high discriminatory power (c-statistic = 0.94; 95% CI 0.92–0.97), and both estimated and observed in-hospital mortalities increased from 1% at score ≤ 5 to almost 100% at score ≥ 14 with linear calibration plots. Conclusions: We developed and validated the mABSI which accurately predicts in-hospital mortality.

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.

Purpose: Data regarding harm from nasal intubation in trauma patients have been conflicting. This study aims to elucidate whether nasal intubation is associated with increased in-hospital mortality compared with oral intubation. Methods: A retrospective cohort study on a nationwide trauma registry of 2004–2019 was conducted. Adult trauma patients who underwent nasal or oral intubation during initial resuscitation were selected. In-hospital mortality and lung complications were compared between nasal and oral intubations. A generalized estimating equation model accounting for within-institution clustering was adopted. Patient demographics, comorbidities, mechanism, injury severity, and vital signs on hospital arrival were adjusted. Subgroup analyses were conducted based on age, Abbreviated Injury Scale [AIS] for the head and face, and vital signs on arrival. Results: Among 29,271 patients eligible for the study, 667 were intubated nasally. In-hospital mortality was higher in nasal intubation compared with oral intubation (OR, 1.28 [95% CI, 1.01–1.64]). There were more noninfectious pulmonary complications in nasal intubation (OR, 1.48 [1.14–1.94]). The harms of nasal intubation were observed only in the elderly (age ≥ 75), patients with severe head injury (AIS in the head ≥ 4), and normotensive patients (systolic blood pressure ≥ 90 mmHg). Conversely, mortality was comparable regardless of the route of intubation in patients with complicated facial injury (AIS in the face ≥ 3). Conclusion: Nasal intubation was associated with increased in-hospital mortality, particularly in older patients and severe head injury, but not severe facial injury. The route of intubation should be judiciously decided during trauma resuscitation.

Introduction: Pump-controlled retrograde trial off (PCRTO) is described as an effective weaning strategy for veno-arterial extracorporeal membrane oxygenation (ECMO) in the guidelines. Contrastingly, there is no established weaning strategy for veno-arteriovenous (V-AV) ECMO. We report a novel application of PCRTO in a patient undergoing V-AV ECMO. Case report: A 49-year-old man had pneumonia and a history of kidney transplantation. Two days after intubation, respiratory failure progressed and veno-venous (V-V) ECMO was introduced. On day 7 after ECMO, the configuration was changed to V-AV ECMO owing to septic cardiomyopathy due to suspected cholangitis. On day 15, with partial haemodynamic improvement and persistent respiratory failure, PCRTO was performed; the patient was safely returned to V-V ECMO. Discussion: In patients undergoing V-AV ECMO, PCRTO could have the potential to accurately simulate decannulation of the arterial cannula. Conclusion: This novel weaning strategy could be considered in patients undergoing V-AV ECMO.

BACKGROUND: Primary fascia closure is often difficult following an open abdomen (OA). While negative-pressure wound therapy (NPWT) is recommended to enhance successful primary fascia closure, the optimal methods and degree of negative pressure remain unclear. This study aimed to elucidate optimal methods of NPWT as a tentative abdominal closure for OA to achieve primary abdominal fascia closure. MATERIALS AND METHODS: A multicenter, retrospective, cohort study of adults who survived OA greater than 48 h was conducted in 12 institutions between 2010 and 2022. The achievement of primary fascia closure and incidence of enteroatmospheric fistula were examined based on methods (homemade, superficial NPWT kit, or open-abdomen kit) or degrees of negative pressure (<50, 50-100, or >100 mmHg). A generalized estimating equation was used to adjust for age, BMI, comorbidities, etiology for laparotomy requiring OA, vital signs, transfusion, severity of critical illness, and institutional characteristics. RESULTS: Of the 279 included patients, 252 achieved primary fascia closure. A higher degree of negative pressure (>100 mmHg) was associated with fewer primary fascia closures than less than 50 mmHg [OR, 0.18 (95% CI: 0.50-0.69), P =0.012] and with more frequent enteroatmospheric fistula [OR, 13.83 (95% CI: 2.30-82.93)]. The methods of NPWT were not associated with successful primary fascia closure. However, the use of the open-abdomen kit was related to a lower incidence of enteroatmospheric fistula [OR, 0.02 (95% CI: 0.00-0.50)]. CONCLUSION: High negative pressure (>100 mmHg) should be avoided in NPWT during tentative abdominal closure for OA.

BACKGROUND: We aimed to identify clinical features of patients who most benefitted from resuscitative endovascular balloon occlusion of the aorta (REBOA). METHODS: Adult patients treated with REBOA were identified in the Japan Trauma Data Bank (2019–2022), and phenotype analyses were conducted. An estimated survival rate was calculated for each patient treated with REBOA adjusting for background and institution characteristics, which was compared with a general probability of survival calculated with Trauma and Injury Severity Score probability of survival. Patients were divided into four groups: notably higher, higher, notably lower, and lower survival than expected (>15% higher, 0–15% higher, ≥15% lower, and 0–15% lower than Trauma and Injury Severity Score probability of survival, respectively) groups. Then, clinical features were identified in patients with notably higher survival as significantly inclining/ declining variables across the groups. In the validation using 2010 to 2018 database, patients with these clinical features were selected, and in-hospital survival was compared between those with and without REBOA. RESULTS: Among 805 patients treated with REBOA, 180 (22.4%) had notably higher, and 240 (29.8%) had higher survival than expected. Glasgow Coma Scale score of ≤6, systolic blood pressure of ≤70 mm Hg, Abbreviated Injury Scale (AIS) in abdomen score of ≥3, and AIS in extremity/pelvis score of ≥4 were identified as the clinical features of patients with notably higher survival than expected. In the validation, 236 patients met all the identified features, and those with REBOA showed higher survival to discharge than those without (8/39 [21.6%] vs. 13/197 [7.3%]; odds ratio, 3.52 [1.34–9.25]) and more frequently underwent laparotomy and angiography for pelvis (odds ratio, 2.52 [1.24–5.11] and 2.31 [1.08–4.95], respectively). CONCLUSION: Patients with Glasgow Coma Scale score of ≤6, systolic blood pressure of ≤70 mm Hg, AIS in abdomen score of ≥3, and AIS in extremity/pelvis score of ≥4 were most likely to benefit from REBOA and had a higher survival rate by >30% than general trauma population treated without REBOA.

Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI. Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival. Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = −0.441, p = 0.017), but not with blood pressure (rho = −0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality. Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI.

Objective: Mass gatherings challenge local healthcare systems due to increased spectator demands. During the Tokyo 2020 Olympic and Paralympic Games, a medical team stationed at the Olympic Stadium implemented an on-site medical system for over 3,000 nonathlete attendees. This study analyzed medical encounters among nonathlete participants and evaluated the system’s effectiveness. Methods: A retrospective descriptive analysis was conducted, reviewing medical records from the on-site medical suite at the Tokyo 2020’s main stadium and from hospitals to which patients were transferred. Data included patient demographics, symptoms, vital signs, diagnoses, treatments, and response times both on-site and at hospitals. Results: Of the 44 patients included, heat-related illness and trauma were the most frequent conditions. Seven (15.9%) patients required hospital transport. Median times recorded were 22 min to the on-site suite, 51 min under the on-site care, and 66 min of prehospital time. Conclusion: The availability of specialized physicians and nurses facilitated efficient triage and early treatment within the on-site setting. This study underscores the importance of medical preparedness for future large-scale gatherings.

Background: We evaluated the outcomes of pediatric patients with blunt liver and spleen injury (BLSI) admitted to hospitals with pediatric intensive care units (PICUs). Methods: A post-hoc analysis of a multicenter observational study on pediatric patients (≤16 years) with BLSI at 83 hospitals between 2008 and 2019 was conducted. Thirty-day mortality and BLSI-associated adverse events were compared between patients treated in hospitals with and without PICUs. Estimated 30-day mortality was compared, adjusting for demographics, comorbidities, injury mechanism and severity, and resuscitative treatments using inverse probability weighting. Results: Among 1401 patients, 421 were treated in hospitals with PICUs and 207 were admitted to a PICU. The 30-day mortality was 3 (0.7 %) and 13 (1.3 %) in patients treated in hospitals with and without PICUs, respectively, and was comparable between the patients treated in PICUs and adult ICUs (1 [0.5 %] vs. 9 [1.9 %]). The adjusted 30-day mortality was lower in patients treated in hospitals with PICUs than in those treated in hospitals with adult ICUs (3 [0.2 %] vs. 13 [1.0 %]; odds ratio 0.22 [0.06–0.79]; p = 0.012) and in those treated in PICUs than in those treated in adult ICUs (2 [0.3 %] vs. 10 [1.5 %]; odds ratio 0.22 [0.05–0.98]; p = 0.041). BLSI-related adverse events were similar regardless of the PICU availability or admission, except for emergency hemostasis of ruptured pseudoaneurysm, which was fewer in patients treated in hospitals with PICUs. Conclusions: Adverse events, including 30-day mortality, were rare, regardless of PICU availability, and the adjusted 30-day mortality was lower in patients treated in PICUs.

Introduction: Injury prevention is valuable for pediatric burns at home. To develop future target of prevention, we aimed to elucidate characteristics and chronological changes of pediatric burn injuries at home in urban areas. Patients and Methods: We conducted a retrospective observational study using the database of the Tokyo Burn Unit Association, which comprises 14 tertiary burn centers, the Tokyo Fire Department, Tokyo Medical Association, and the Tokyo city government. We included pediatric patients aged ≤ 15 years who had a burn injury at home in the last 30 years and divided them into five groups at 6-year intervals. We compared the mechanism, severity, and outcome of burn injuries between the groups. Results: We included 1092 pediatric patients, with no significant chronological changes in the incidence of burn injuries at home (approximately 200 patients in each 6-year period). The median age was 1 year in all the groups. Flame burns decreased from 7.7 % to 1.6 %, whereas scald burns remained at > 80 %. The burn area decreased from 10 (5−16) % total body surface area (%TBSA) to 7 (3−11) %TBSA. The length of hospital stay was reduced from 6 to 2 days, and in-hospital mortality was 0.4–0.5 % in the last decade. Conclusions: The incidence of flame burns and burn area decreased over time with improving clinical outcomes in pediatric burns. The number of scald burns remained the same over time; thus, further social intervention is needed to prevent scald burns.

Introduction Traumatic brain injury (TBI) often causes permanent neurological dysfunction. Although no medication has been validated yet to prevent secondary injury of brain tissue, recent animal studies have reported that perampanel, a glutamine receptor antagonist, could improve the neurological functions of animals with TBI by mitigating the abnormal calcium influx and cell death around the site of primary injury. The present study aims to elucidate the efficacy of perampanel administration in improving the neurological function of patients with TBI. Methods and analysis The perampanel for alleviation of secondary injury in TBI trial is a multicentre, phase-II, open-label randomised controlled trial targeting patients with mild-to-moderate TBI. This trial will include adult TBI patients with a Glasgow Coma Scale score of 9-14 from five tertiary centres. Patients with epilepsy as a comorbidity, delayed presentation of symptoms (>24 hours after injury) or Injury Severity Score of ≥25 will be excluded. The study participants will be randomly assigned to either the perampanel group (2 mg/day) or the control group (fosphenytoin administered at a dose of 15-18 mg/kg/day, followed by 5-7.5 mg/kg/day of fosphenytoin). In both groups, the medication will be initiated within 12 hours of the TBI diagnosis and continued for 7 days. The antiepileptic drugs can be increased, changed or added as necessary if early post-traumatic seizures are observed. The primary outcome is favourable neurological outcome, defined as a Glasgow Outcome Scale Extended score of ≥5 at 90 days after the TBI diagnosis, which will then be compared between the groups through an intention-to-treat analysis. Ethics and dissemination The present study has been approved by the Certified Review Board of Keio at the principal institution (approval number: N20240004). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations. Trial registration number Japan Registry of Clinical Trials (jRCTs031250067).